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[ "12876172", "9516090", "19651542", "20884302", "8148194", "9192926", "16839826", "9106575", "18759658", "12737683", "9426082", "1750018", "12527599", "12493338", "7606951", "3406919" ]

[ "Comparison of lung deposition of colomycin using the HaloLite and the Pari LC Plus nebulisers in patients with cystic fibrosis.", "Effect of smaller droplet size of dornase alfa on lung function in mild cystic fibrosis. Dornase Alfa Nebulizer Group.", "Pharmacokinetics and safety of tobramycin administered by the PARI eFlow rapid nebulizer in cystic fibrosis.", "Lung deposition of inhaled tobramycin with eFlow rapid/LC Plus jet nebuliser in healthy and cystic fibrosis subjects.", "Aerosol deposition in cystic fibrosis using an aerosol conservation device and a conventional jet nebulizer.", "An evaluation of two aerosol delivery systems for rhDNase.", "Nebulisers comparison with inhaled tobramycin in young children with cystic fibrosis.", "A comparison of peak sputum tobramycin concentration in patients with cystic fibrosis using jet and ultrasonic nebulizer systems. Aerosolized Tobramycin Study Group.", "Aerosolization of tobramycin (TOBI) with the PARI LC PLUS reusable nebulizer: which compressor to use? Comparison of the CR60 to the PortaNeb compressor.", "Lung deposition in cystic fibrosis patients using an ultrasonic or a jet nebulizer.", "Comparison of drug delivery from conventional versus \"Venturi\" nebulizers.", "Pulmonary deposition of nebulised amiloride in cystic fibrosis: comparison of two nebulisers.", "Efficiency of pulmonary administration of tobramycin solution for inhalation in cystic fibrosis using an improved drug delivery system.", "A widely available method for the assessment of aerosol delivery in cystic fibrosis.", "Comparison of three jet nebulizer aerosol delivery systems used to administer recombinant human DNase I to patients with cystic fibrosis. The Pulmozyme rhDNase Study Group.", "Deposition of carbenicillin aerosols in cystic fibrosis: effects of nebuliser system and breathing pattern." ]

[ "To examine the effectiveness of delivery of nebulised colistin by the HaloLite nebuliser compared to the Pari LC Plus in patients with cystic fibrosis.\n Randomised crossover trial of 15 patients aged >6 years. Inhalation of one mega unit of colistin in 3 ml diluent, labelled with technetium-99m DTPA, was used to assess lung deposition. The Pari was nebulised to dryness and one button press of the HaloLite was completed. Following a seven day washout period, patients inhaled colistin twice daily for seven days through the first device. Sputum specimens were analysed for colistin levels and pseudomonas load. This procedure was repeated with the alternative device.\n Lung uptake of radiolabelled colistin was significantly higher with the Pari. However, lung uptake calculated as a percentage of the amount of drug used was significantly higher for the HaloLite. Time to nebulise was significantly shorter with the HaloLite. Sputum levels of colistin were higher following use of the Pari; this was close to significance.\n The manufacturer's recommended dosages for nebulising antibiotics with a HaloLite result in a lower delivery than patients receive when using a Pari nebuliser. The concept of adaptive aerosol delivery has several theoretical advantages but the recommended doses for the HaloLite need to be modified in order to improve effectiveness.", "Aerosolized recombinant human DNase (dornase alfa) reduces mucus viscoelasticity in vitro and improves pulmonary function in patients with cystic fibrosis (CF). We postulated that if dornase alfa could be delivered more peripherally to small airways in the lung in the form of smaller aerosol droplets in patients with early airway obstruction, the increase in pulmonary function from baseline might be improved. CF patients (n = 749) with mild lung disease (baseline forced vital capacity > or = 70% predicted) were randomly assigned to receive dornase alfa 2.5 mg daily for 2 weeks by one of two nebulizer systems: 1) the Medic-Aid Durable SideStream nebulizer powered by the MobilAire Compressor (SS/MA) producing a droplet size with a mass median aerodynamic diameter (MMAD) of 2.1 microm; or 2) the Hudson T Up-draft nebulizer with a DeVilbiss Pulmo-Aide compressor (HT/PA) with an MMAD of 4.9 microm. Spirometry was performed at baseline and following 14 days of treatment. Dornase alfa delivered by both nebulizer systems produced small but statistically significant improvements in pulmonary function compared with baseline. There was a trend (P = 0.06) toward greater improvement in forced expiratory flow in 1 s in the SS/MA group (4.3%) compared with the HT/PA group (2.5%). These results indicate that the short-term spirometric response to dornase alfa is influenced in part by the physical characteristics of the aerosol in patients with mild lung disease. We speculate that this may be true for other therapeutic aerosols, and it appears that localization of disease in the lung plays a role in the response to inhaled agents.", "Nebulization times have been identified as an issue in patient compliance with tobramycin solution for inhalation (TSI) therapy in cystic fibrosis (CF).\n In this randomized, open-label, multicentre, two-period, crossover study, patients (n=25) with CF and chronic pulmonary pseudomonal infection received TSI for 15 days via eFlow rapid or LC PLUS nebulizer. Nebulization times and sputum/serum tobramycin concentrations were determined, and safety evaluated.\n Nebulization times were significantly shorter for eFlow rapid versus LC PLUS on Day 1 (least squares mean estimate of the difference -10.5 min, 95% confidence intervals [CI] -12.6, -8.3, p<0.0001) and Day 15 (difference -7.7 min, 95% CI -9.0, -6.5, p<0.0001). Broadly comparable sputum/systemic exposure to tobramycin was observed and the incidence of adverse events was similar for both nebulizers.\n Use of the eFlow rapid nebulizer reduced TSI nebulization time. The systemic exposure to tobramycin appeared to be broadly similar in this exploratory study.", "Reducing nebulisation times for tobramycin solution for inhalation in cystic fibrosis (CF) may improve compliance.\n In this single-dose, open-label, two-way crossover study, 13 subjects (7 CF, 6 healthy) were randomised to receive tobramycin via eFlow rapid or LC Plus jet nebuliser. Drug deposition in the lung using gamma scintigraphic imaging, nebulisation times, pharmacokinetics, and safety were evaluated.\n In CF patients, whole-lung deposition was 40% less with the eFlow rapid compared with LC Plus nebulisers was (8.9±0.8%, and 15.1±6.0%, p>0.05). Nebulisation time was shorter with eFlow rapid compared to LC Plus (7.0min versus 20.0min, p<0.05). Lung deposition in healthy subjects was comparable between both devices.\n eFlow rapid reduces the nebulisation time of tobramycin and can potentially improved compliance in patients with CF.\n Copyright © 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.", "The deposition of technetium radiolabelled aerosol within the lungs of 12 stable cystic fibrosis patients (mean age 12.7 years) was compared using the Acorn nebulizer and mouthpiece alone, and the Acorn nebulizer attached to the Mizer Aerosol Conservation Device (MACD). The total activity delivered to the patient using the MACD was 11.1% (+/- 7.8% s.d.) of the initial dose, compared to 5.8% (+/- 4.2% s.d.) with the nebulizer and mouthpiece alone (P < 0.05). With the MACD, 84% of the intrapulmonary dose was delivered to the peripheral regions, compared to 76.5% with the nebulizer and mouthpiece (P < 0.05). No significant correlation was found between aerosol deposition and pulmonary function. The Mizer Aerosol Conservation Device significantly increases both total intrapulmonary aerosol deposition and peripheral aerosol distribution.", "Increasingly, proteins are delivered to the respiratory tract as an aerosol, and clinical efficacy is dependent on optimal delivery of the protein in an intact form. The object of this study was to compare the in vivo and in vitro results of two aerosol delivery systems for the aerosolization of recombinant human deoxyribonuclease I (rhDNase) in patients with cystic fibrosis (CF). Patients with CF who were to be initiated on rhDNase were randomized either to the Hudson nebulizer and Pulmo-Aide compressor or to the Sidestream nebulizer driven by the CR50 air compressor. An in vitro study was performed in six sets of the two aerosol delivery systems. One hundred and seventy three patients were randomized in this open study, where rhDNase was administered for 7 days. Improvements in pulmonary function were observed in both groups following 1 week of therapy with rhDNase. Changes in the Sidestream/CR50 and Hudson/Pulmo-Aide groups, respectively, were: 16 and 11% for forced expiratory volume in one second (p=0.14); 12 and 10% for forced vital capacity (p=0.70); and 14 and 7% for forced expiratory flow at 25-75% of expiration (FEF(25-75)) (p=0.18). A greater proportion of patients in the Sidestream/CR50 group (58%) had a >10% response in FEF(25-75) compared to the Hudson/Pulmo-Aide group (42%; p=0.03). The Sidestream nebulizer had a faster nebulization rate (p<0.05), lower mass median diameter for the aerosol mass produced (p<0.001), higher percentage of particles in the respirable range (p<0.001) and greater respirable output (p<0.005), compared to the Hudson nebulizer. The Sidestream/CR50 combination is a quicker, more efficient system in vitro than the Hudson/Pulmo-Aide combination, whereas the in vivo study only suggested a difference. Clinically, the two systems have similar efficacy.", "This randomised cross-over pilot study was undertaken in 10 cystic fibrosis children aged 10 to 63 months to describe lung absorption of tobramycin delivered by the PariLC+/PariTurboboyN (Pari GmbH) and the disposable NL9M/AtomisorBoxPlus (Diffusion Technique Française) nebulising systems.\n Each child inhaled 300 mg tobramycin delivered with one or the other apparatus via a facemask in two separate and standardised sessions. Urine was collected for 6 h. Tobramycin concentrations determined by immunoprecipitation were expressed in mg per g of creatinine and compared by a Wilcoxon test for matched pairs. The influences of age, weight and Brasfield score on this parameter were evaluated by correlation tests, and those of sex, previous nebulisation treatment, and crying or coughing were evaluated by Student's t-test.\n The amount of tobramycin measured in urines was low and variable. Median values for urinary tobramycin concentration were 47.6 mg/g (14.9-79.6) with the PariLC+ and 42.6 mg/g (6.3-112.8) with the NL9M (p=0.6). PariLC+ delivered tobramycin in 22 min and NL9M in 12 min (p=0.005). Crying or coughing dramatically reduced the amount of tobramycin collected.\n This pilot study shows that evaluation of nebulisers based on tobramycin renal excretion is feasible in young children with cystic fibrosis.", "To determine whether adequate concentrations of a new formulation of tobramycin could be delivered to the lower respiratory tract of patients with cystic fibrosis (CF) using a jet nebulizer delivery system.\n A multicenter, open-label, randomized, crossover study.\n Ten tertiary care, university-affiliated, teaching hospitals in the United States.\n Sixty-eight patients recruited from 10 CF Foundation centers and who were at least 8 years of age, had a diagnosis of CF, and expectorated daily sputum. No control subjects enrolled.\n Each patient received one administration of aerosolized tobramycin from each of the three nebulizer systems in random order. Each administration was separated by a minimum of 48 h. The two jet nebulizer systems tested were the Sidestream (Medic-Aid; Sussex, UK), and the Pari LC (Pari Respiratory Equipment; Richmond, Va), with a DeVilbiss Pulmoaide compressor (DeVilbiss Health Care; Somerset, Pa), both administering 300 mg tobramycin in 5 mL of 1/4 normal saline solution (NS). Patients were also administered 600 mg tobramycin in 30 mL of 1/2 NS with the UltraNeb 99/100 (DeVilbiss).\n Sputum and serum tobramycin concentration and pulmonary function were monitored. An adequate peak sputum tobramycin concentration was defined as > 128 microg/g sputum at any of three time points (10, 60, or 120 min) after completion of treatments.\n The peak tobramycin concentrations in expectorated sputum were 687+/-663 microg/g (mean+/-SD) with the Pari LC and 489+/-402 microg/g with the Sidestream. Adequate peak sputum tobramycin concentration was achieved in 93% of the patients with the Sidestream, and in 87% of the patients with the Pari LC. Peak sputum concentrations were found to be substantially higher when patients received tobramycin administered with the UltraNeb 99/100, 1,498+/-1,331 microg/g with 30% of patients having levels exceeding 2,000 microg/g. Serum tobramycin concentrations were < or = 4 microg/mL for all patients following administration with each nebulizer.\n Adequately high sputum tobramycin concentrations were documented in sputum in > 85% of patients following the administration of 300 mg/5 mL formulation of tobramycin aerosolized by the two jet nebulizer delivery systems, Sidestream and Pari LC. The single tobramycin administration delivered by these two systems is well-tolerated.", "Aerosol output, aerosol output rate, and aerosol size distribution are influenced by the compressed air flow rate through the nebulizer cup. Testing a nebulizer-compressor with a drug for inhalation in cystic fibrosis (CF) patients is mandatory prior to starting therapy. Tobramycin solution for inhalation (TSI), TOBI, is licensed in Europe with a recommendation for a \"suitable\" compressor connected to the PARI LC Plus nebulizer. To select a compressor, five devices were tested in a previous in vitro study and this resulted in a subsequent in vivo study. Two compressors [CR60 and PortaNeb (PN)] were compared in an open, randomized, crossover single dose pilot study in 10 CF patients to assess the most suitable device for inhalation of a tobramycin solution (TSI), TOBI, with the PARI LC Plus nebulizer. Lung function (FEV1 and FVC), pharmacokinetics [PK; safety (Cmax, Ctrough)], lung deposition (indirect method AUC0-6), nebulization time, and patients' experiences (questionnaire) were determined and compared. It was found that values of Cmax and AUC0-6 were higher with the CR60 than with the PortaNeb: 0.70 versus 0.54 mg/L, p = 0.005, and 2.54 versus 2.01 h.mg/L, p = 0.017, respectively. Tmax after use of the CR60 appeared earlier (0.64 vs. 0.85 h, p = 0.005). Transient airway narrowing was measured in three patients (2 x PN;1 x CR60) versus subjective chest tightness in seven patients (CR60 > PN). A shorter nebulization time for CR60 of 13.2 min compared to PN 16.1 min (p = 0.022) was observed, which was the main reason why patients preferred the CR60 (n = 7). No toxic serum levels were reached after inhalation of TSI. The CR60 compressor may seem advantageous based on a higher lung deposition and a shorter nebulization time, but a study in a large CF population to provide information on a possible higher risk of toxicity of TSI is called for.", "This study was conducted to compare pulmonary deposition following inhalation with an ultrasonic and a jet nebulizer in CF patients under conditions relevant to practice. The marker substance used to estimate the relative lung bioavailability was sodium cromoglycate (SCG), which is poorly absorbed from the gastrointestinal tract, but is completely absorbed from the lungs. Ten CF patients (aged 9-21 years) used an ultrasonic nebulizer (Multisonic compact 2.4 MHz) and a jet nebulizer (Parimaster, LC Plus Turbo) in a crossover design to inhale a solution containing 20 mg of SCG and a beta(2)-agonist. Urine was collected in five fractions until 12 h p. a., and the excreted SCG was determined by means of HPLC. Prior to each inhalation, the patients' pulmonary function was measured employing a Pneumoscope. Using the ultrasonic nebulizer, the amount of SCG excreted in urine was significantly greater than that after inhalation with the jet nebulizer (1.43 +/- 0.47 mg vs. 1.04 +/- 0.47 mg; p = 0.002), despite the larger residual volume in the ultrasonic nebulizer. The absorption half-life for SCG following ultrasonic nebulization was significantly shorter when compared with jet nebulization (84 +/- 14 min vs. 101 +/- 19 min; p = 0.005), being suggestive of a more peripheral deposition. Furthermore, an inverse relationship was found between absorption half-life and FEV(1) (% pred.) (r = -0.655, p = 0.04) or MMEF(75/25) (% pred.) (r = -0.844, p = 0.031), but only with the ultrasonic nebulizer. In conclusion, the ultrasonic nebulizer tested when used for inhalation in CF patients was found to be at least equivalent to the jet nebulizer.", "Attempts to improve drug delivery from conventional jet nebulizers have included the use of storage systems to reduce drug wastage during exhalation. Venturi nebulizers enhance drug delivery during inhalation, reducing treatment times and drug wastage. This study investigated the effect of age on inhaled dose from a conventional jet nebulizer (Acorn) used both with and without a storage chamber (Mizer), compared to two Venturi nebulizers (Ventstream and Pari LC). Filters were attached to the four nebulizer systems, containing salbutamol, and 18 children with cystic fibrosis (3-16 yrs) inhaled through these devices. The quantity of drug collected on the filter was assessed using ultraviolet spectrophotometry. The particle size distribution of the aerosol from each nebulizer system was measured using laser diffraction. Inspiratory filter deposition using the Acorn was lower than the Acorn with Mizer, and both Venturi nebulizers. Filter deposition using the Acorn with Mizer was lower than the Pari LC. No trend with age, height or weight was noted using any nebulizer. Aerosol particle size using the Ventstream was lower than the other nebulizer systems. Drug output from both Venturi nebulizers was more efficient than from the jet nebulizer, used with and without the storage chamber, during inhalation by children with cystic fibrosis. The inhaled dose did not change with the patient's age or size using both types of nebulizer.", "BACKGROUND Preliminary evidence suggests that regular inhalation of nebulised amiloride reduces sputum viscoelasticity, increases the clearance of sputum by mucociliary mechanisms and by coughing and reduces the rate of deterioration in lung function in patients with cystic fibrosis. These effects depend on adequate delivery of amiloride to the airways. This study was performed to quantify and compare pulmonary deposition of amiloride produced by two different nebuliser systems. METHODS The pulmonary deposition of nebulised amiloride (1 mg in 3 ml saline) was measured in eight patients with cystic fibrosis when given via a jet (System 22 with CR 60 compressor) and an ultrasonic (Fisoneb) nebuliser. Human serum albumin labelled with technectium-99m was used as an indirect marker for amiloride and its deposition in the lung was detected with a gamma camera. RESULTS Amiloride inhalation caused no side effects or changes in spirometric indices. The mean (SD) total pulmonary amiloride deposition was 57 (24) micrograms with the System 22 and 103 (53) micrograms with the Fisoneb nebuliser. Pulmonary deposition was completed more rapidly with the Fisoneb (4-5 minutes) than with the System 22 nebuliser (7-8 minutes) and the Fisoneb was preferred by the patients. CONCLUSIONS Both nebulisers appeared to deliver adequate amounts of amiloride to the lungs, but treatment with the Fisoneb nebuliser was quicker, more efficient, and more acceptable to the patients. Of the two nebulisers assessed, the Fisoneb would be preferred for clinical trials.", "To determine whether tobramycin solution for inhalation (TSI) can be administered safely and more efficiently with a new-generation aerosol device, the AeroDose 5.5 RP inhaler (Aerogen; Mountain View, CA) than with the approved PARI LC PLUS nebulizer (PARI Respiratory Equipment; Monterey, CA) with Pulmo-Aide compressor (DeVilbiss Corp; Somerset, PA). Second, we wanted to ascertain which AeroDose-delivered tobramycin dose is equivalent to the standard 300-mg dose administered with the PARI LC PLUS.\n Open-label, randomized, multicenter, single-dose, three-period, four-treatment, active- control, crossover trial.\n Nine US cystic fibrosis (CF) centers.\n Fifty-three patients >or= 12 years of age with a confirmed diagnosis of CF, the ability to expectorate sputum, and FEV(1) of >or= 40% of predicted.\n Subjects inhaled three single doses of TSI at 1-week intervals, as follows: conventional control treatment, 300 mg via the PARI LC PLUS; and two of three experimental treatments, 30, 60, or 90 mg via the AeroDose. FEV(1) was measured before and after dosing. After each dose, sputum and serum samples were collected at various intervals for 8 h, and urine was collected for 24 h to estimate lung and systemic tobramycin delivery.\n There were no significant differences between treatments in the change in FEV(1) 30 min after dosing or in the frequency of adverse events. Sputum and serum levels of tobramycin produced by the AeroDose 90-mg dose treatment approximated those achieved with the PARI LC PLUS 300-mg dose treatment. Nebulization times using the AeroDose inhaler were < 50% those of the PARI LC PLUS.\n Compared with the standard nebulizer, the AeroDose safely achieved an approximately threefold greater efficiency in the delivery of TSI to the lungs in less than half the time.", "Whilst nebulisers are commonly used in the treatment of cystic fibrosis (CF), nebulised aerosol lung deposition in individual patients is not routinely assessed in clinical practice. The present study was designed to evaluate whether a comparative measurement of aerosol lung deposition from nebulisers using a widely available scintigraphic method could be employed to assist the selection of the best system for individual patients. Lung deposition of the radiolabelled aerosol from the Pari LC Plus (Pari Medical Ltd) nebuliser and the HaloLite Adaptive Aerosol Delivery (AAD) system (Profile Therapeutics Ltd) was measured using planar scintigraphy in 10 healthy volunteers and 6 CF patients. The HaloLite AAD delivered on average 2.1 times (P=0.003) as much aerosol to the lungs compared with Pari LC Plus. Only two subjects had higher lung deposition from Pari LC Plus than HaloLite AAD system. There was marked inter-individual variation in the deposition pattern in CF patients. The aerosol deposition from HaloLite AAD had higher central distribution than that obtained with the Pari LC Plus. The overall intersubject variability of the delivered dose was 56% with Pari LC Plus and 24% with HaloLite AAD (P<0.05). The measurement of aerosol deposition from nebulisers can be performed using a simple and widely available methodology, and may improve nebuliser selection in CF patients.", "To compare the degree of improvement in pulmonary function achieved with recombinant human DNase I (rhDNase) administered by three different aerosol delivery systems: DeVilbiss Pulmo-Aide compressor with the Marquest Acorn II nebulizer, the Hudson T Up-draft nebulizer, and the Pari LC Jet Plus nebulizer with the Pari Inhalier Boy compressor. These produce similar aerosols in vitro in terms of size distribution and activity of delivered rhDNase.\n Multicenter, randomized, open-label, parallel-group comparison of changes from baseline in pulmonary function variables in each test group. Patients were treated with rhDNase (2.5 mg bid) for 15 days, administered with three different aerosol delivery systems.\n Outpatient clinics at 26 sites in the United States.\n 397 patients > 5 years of age with cystic fibrosis and baseline forced vital capacity (FVC) values between 40 and 70% of predicted values.\n All three nebulizers gave comparable improvements in pulmonary function. FEV1 increased by an average of 13.2 to 14.1%, FVC by 10.9 to 11.8% and forced midexpiratory flow (FEF25-75) by 16.5 to 17.1%. No unusual or unexpected adverse events were reported other than those that would be expected in patients with cystic fibrosis.\n Recombinant human DNase I produced a similar magnitude of improvement in the pulmonary function of patients with cystic fibrosis when the drug was administered using three different types of nebulizer systems with similar in vitro delivery and safety characteristics.", "Antibiotic aerosol treatment is successful in treating Pseudomonas infection in some patients with cystic fibrosis, but the amount of drug reaching the lungs is unknown. The deposition patterns of carbenicillin aerosols delivered from two commercially available nebuliser systems (the Turret nebuliser plus Maxi compressor and the Inspiron nebuliser plus Traveller compressor) have been compared in six patients with cystic fibrosis during tidal breathing. The aerosol mass median diameters were 3.2 and 7.3 microns. In addition, the aerosol from the Turret-Maxi nebuliser system was inhaled by a combination of tidal and deep breathing. After two minutes' breathing via a mouthpiece the mean (SEM) deposition in the lungs was 15.60 (1.5) mg carbenicillin with the Turret nebuliser plus Maxi compressor, but only 6.54 (1.09) mg with the Inspiron nebuliser plus Traveller compressor; the distribution pattern within the lung was significantly more peripheral with the former nebuliser system. These differences may be ascribed partly to the smaller droplet size from the Turret system and partly to the higher nebulisation rate from the more powerful Maxi compressor. Tidal plus deep breathing produced a further small but non-significant increase in lung aerosol deposition. A seventh patient, who failed to complete the trial, had little aerosol deposited in his lungs because he inhaled through his nose. These results emphasise the importance of correct selection of nebuliser equipment for antibiotic aerosol treatment." ]

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[ "Fate of abstracts published in the proceedings of the first annual Perinatal Society of Australia and New Zealand Congress in 1997.", "Lost information? The fate of papers presented at the 40th society for Social Medicine Conference.", "Full publication of results initially presented in abstracts. A meta-analysis.", "Methodologists and their methods. Do methodologists write up their conference presentations or is it just 15 minutes of fame?", "Pattern of publication of ophthalmic abstracts in peer-reviewed journals.", "[Publication rate of original papers orally presented at the Journées Françaises de Radiologie 1996].", "Whatever happened to abstracts from different sections of the association for research in vision and ophthalmology?", "Publication bias in presentations to the Annual Scientific Congress.", "Factors associated with acceptance and full publication of GI endoscopic research originally published in abstract form.", "Publication rates of abstracts from two pharmacy meetings.", "Publication of abstracts presented at diabetes meetings.", "Publication rate of abstracts presented at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery.", "A cohort study of summary reports of controlled trials.", "Publication patterns of presentations at the Society of Teachers of Family Medicine and North American Primary Care Research Group annual meetings.", "Publication pattern of papers presented at the American Society for Surgery of the Hand annual meeting.", "The fate of neuroradiologic abstracts presented at national meetings in 1993: rate of subsequent publication in peer-reviewed, indexed journals.", "Outcomes of cytopathology studies presented at national pathology meetings.", "Positive-outcome bias and other limitations in the outcome of research abstracts submitted to a scientific meeting.", "Fate of cardiology research originally published in abstract form.", "Scientific presentations and their publication. Experience over a 10-year period in the Argentine Division of the I.A.D.R.", "Publication rates of abstracts presented at the 1993 annual Academy meeting.", "Abstracts of trials presented at the Vth World Congress of Psychiatry (Mexico, 1971): a cohort study.", "Published or perished: what becomes of papers presented at oncology nursing society congresses?", "[Publications derived from free communications at the XX Congress of the Anesthesiology and Resuscitation Spanish Association (Anesthesia 92)].", "[The scientific value of society reports in the Nederlands Tijdschrift voor Geneeskunde].", "Fate of abstracts from the Paris 1995 European Society of Anaesthesiologists meeting.", "Abstracts of randomized controlled trials presented at the society for pediatric research meeting: an example of publication bias.", "Do presenters to paediatric meetings get their work published?", "Publication rate of abstracts presented at the annual meeting of the Orthopaedic Research Society.", "Full publication of trials initially reported as abstracts in the Australian and New Zealand Journal of Medicine 1980-2000.", "Scientific abstracts at the Society for Adolescent Medicine meetings: a 3-decade comparison.", "Peer-reviewed publication following presentation at a regional surgical meeting.", "Publication rates of scientific papers presented at the Otorhinolarygological Research Society meetings.", "Time to publication as full reports of abstracts of randomized controlled trials in cystic fibrosis.", "Publication rates following pancreas meetings.", "Converting conference presentations into publications.", "Research outcomes in British gastroenterology: an audit of the subsequent full publication of abstracts presented at the British Society of Gastroenterology.", "Publication of presented abstracts at annual scientific meetings: a measure of quality?", "Do paediatric research presentations at local meetings get published?", "A survey of the publication history of randomly selected IADR/AADR abstracts presented in 1983 and 1984.", "Publication of abstracts presented at anaesthesia meetings.", "An observational study of orthopaedic abstracts and subsequent full-text publications.", "Publication bias in gastroenterological research - a retrospective cohort study based on abstracts submitted to a scientific meeting.", "Fate of abstracts presented at five International Conferences on Pharmacoepidemiology (ICPE): 1995-1999.", "Publication patterns of papers presented at the Annual Meeting of The American Academy of Orthopaedic Surgeons.", "Publications resulting from anesthesia meeting abstracts.", "Factors associated with failure to publish large randomized trials presented at an oncology meeting.", "The publication rates of presentations at major Spine Specialty Society meetings (NASS, SRS, ISSLS).", "Publication of research presented at the pediatric meetings. Change in selection.", "Post-convention dissemination of papers presented at ASHA National Conventions, 1967-1976: stuttering, hearing aids, and alaryngeal speech.", "Conversion rate of research abstracts to publications in pediatric dentistry.", "Abstract to publication ratio for papers presented at scientific meetings: how does emergency medicine compare?", "Resident research projects: frequency of presentation and publication in a national forum.", "[Fate of presentations given at German anesthesia congresses].", "Publication of abstracts submitted to the annual meeting of the Pediatric Orthopaedic Society of North America.", "Randomized controlled trials in pediatric surgery: could we do better?", "Publication rates for the scientific sessions of the OTA. Orthopaedic Trauma Association.", "The publication outcome for the papers presented at the 1990 ABA conference." ]

[ "To examine the fate of research presented at the first annual Perinatal Society of Australia and New Zealand (PSANZ) Congress in 1997, by determining: the rate of publication in peer-reviewed biomedical journals; publication rate by discipline; journals in which work was published; concordance for aims, conclusions, authors and number of study subjects; and time from presentation to publication.\n A MEDLINE search was conducted for any publication in a peer-reviewed journal resulting from a publishable abstract from the proceedings of the first annual PSANZ Congress in 1997. Searching was completed 42 months post-congress. The concordance of aims, conclusions, authors and number of subjects between abstract and published paper was determined.\n There were 172 publishable abstracts in the proceedings of the PSANZ Congress in 1997, and 78 (45%) were published as 83 articles. Basic sciences had the highest publication rate (67%) and midwifery the lowest (20%). Articles were published in 41 journals, with one-third of the articles in three paediatric journals. There was a match with aims in 75%, and with conclusions in 65%. There were 47/77 with the same number of subjects, 20/77 with more and 10/77 with fewer. There were 22 articles with one author added, 12 had more than one author added, 11 had one author removed and five had more than one author removed. Median time-to-publication was 18 months (interquartile range 9-26 months).\n A publication rate of 45% is comparable to other conferences. Basic science and neonatology had the highest publication rates. There were considerable differences between abstract and published article in terms of aims, conclusions, number of subjects and authors.", "nan", "To estimate the rate of full publication of the results of randomized clinical trials initially presented as abstracts at national ophthalmology meetings in 1988 and 1989; and to combine data from this study with data from similar studies to determine the rate at which abstracts are subsequently published in full and the association between selected study characteristics and full publication.\n Ophthalmology abstracts were identified by review of 1988 and 1989 meeting abstracts for the Association for Research in Vision and Ophthalmology and the American Academy of Ophthalmology. Similar studies were identified either from reports contained in our files or through a MEDLINE search, which combined the textword \"abstract\" with \"or\" statements to the Medical Subject Headings ABSTRACTING & INDEXING, CLINICAL TRIALS, PEER REVIEW, PERIODICALS, MEDICAL SOCIETIES, PUBLISHING, MEDLINE, INFORMATION SERVICES, and REGISTRIES.\n Ophthalmology abstracts were selected from the meeting proceedings if they reported results from a randomized controlled trial. For the summary study, similar studies were eligible for inclusion if they described followup and subsequent full publication for a cohort of abstracts describing the results of any type of research study. All studies had to have followed up abstracts for at least 24 months to be included.\n Authors of ophthalmology abstracts were contacted by letter to ascertain whether there was subsequent full publication. Other information, including characteristics of the study design possibly related to publication, was taken from the abstract. For the summary study, rates of full publication were taken directly from reported results, as were associations between study factors (ie, \"significant\" results and sample size) and full publication.\n Sixty-six percent (61/93) of ophthalmology abstracts were published in full. Combined results from 11 studies showed that 51% (1198/2391) of all abstracts were subsequently published in full. Full publication was weakly associated with \"significant\" results and sample size above the median.\n Approximately one half of all studies initially presented in abstract form are subsequently published as full-length reports. Most are published in full within 2 years of appearance as abstracts. Full publication may be associated with \"significant\" results and sample size.", "To assess the extent to which abstracts of methodological research, initially presented at meetings on systematic reviews, have gone on to be published as full articles.\n Full publication was assessed in three ways: a search was carried out of The Cochrane Library; a search was conducted using MEDLINE; and a questionnaire was sent to the contact author of each abstract.\n Approximately half of the abstracts had not been, or were unlikely ever to be, published in full.\n The rate of full publication of abstracts related to the methodology of systematic reviews seems similar to that for randomized trials.", "Presentation of research work at scientific meetings and professional societies is an important first step toward effective scientific communication of research results. To determine the current publication patterns of abstracts, a computerized MEDLINE literature search was performed on 175 randomly selected ophthalmic clinical and basic science abstracts published in conjunction with two ophthalmic national meetings. This search revealed that 105 abstracts (60%) led to full-length articles in peer-reviewed journals within 50 to 56 months of the meeting date. A median interval of 13 months occurred from date of abstract publication to acceptance of the corresponding article. Most articles appeared within 3 years of abstract presentation. Sixty-four percent (48 of 75) of the posters and free papers presented at the annual meeting of the American Academy of Ophthalmology in November 1984 led to full-length articles, as did 57% (57 of 100) of the abstracts presented at the annual meeting of the Association for Research in Vision and Ophthalmology in May 1985. These findings emphasize the preliminary nature of abstracts. The fact that nearly 60% of abstracts are published reflects favorably on the review process of both meetings.", "The purpose of the present study was to determine the publication rate in Medline-indexed journals of papers originally presented at the Journées Françaises de Radiologie (JFR96).\n Proceedings from the JFR 96 were reviewed by two observers in conference. A Medline search encompassing 1997-1999 was performed for the lead author of all abstracts of original papers. Publication year and the journal of publication were recorded.\n 456 oral presentations were analysed, 39 papers were subsequently published corresponding to a publication rate of 8.5%. 10 papers were published in Radiology, 4 in European Radiology and 4 in the Journal de Radiologie, the other 21 in other journals. Publication rate was significantly higher for two sessions: Research session (publication rate was 22%) and Bone and Joint session (publication rate was 16%).\n Less than 10% of abstracts presented at JFR 96 were subsequently published in Medline-indexed journals. This rate is lower than the publication rate of papers presented at other medical meetings.", "The authors investigated the fate of abstracts from each ARVO section (May 1985 meeting), the overall publication percentage, and the journals in which the abstract-derived articles were published.\n They performed a MEDLINE search by first author for 25 or 26 randomly selected abstracts from each section to identify those that led to full-length articles in peer-reviewed journals.\n Overall, 63% of abstracts led to full-length articles in peer-reviewed journals within our search period of 87 months. The publication rate of oral presentation abstracts (68%) was significantly higher than that of poster presentation abstracts (56%). A greater proportion of basic science-oriented abstracts (67%) led to publication than the clinically oriented abstracts (56%). The rate of publication was lowest for the Cornea section (40%) and highest for Physiology and Pharmacology (80%) and Biochemistry (76%). The abstract-derived articles were published in 67 different peer-reviewed journals, with 43% of the articles appearing in only five journals.\n The fact that the majority of abstracts led to full-length articles supports ARVO's goal of a large interdisciplinary appeal with the exchange of ideas among different investigators.", "Free papers presented to the Annual Scientific Congress (ASC) of the Royal Australasian College of Surgeons (RACS) were reviewed for the years 1994, 1995 and 1996. Reports were examined for evidence of publication bias.\n Suitable free papers were identified from the proceedings of the meetings and authors were contacted to obtain information about the research reported and any publications resulting from it.\n Responses were obtained from 302 of 576 presentations considered suitable. A total of 55% of responding authors reported publication of their paper. Basic science papers were most likely to be published. There was a significant bias in favour of publication of positive results (98 of 139 positive vs 76 of 159 inconclusive or negative reports; P < 0.01). Retrospective data were as likely to be published as prospective (51% and 57%, respectively). Reports describing studies of high-level evidence were more likely to be published in journals with a high impact factor.\n The ASC is a comprehensive meeting that attracts a wide range of free papers from most sections of the RACS. There appears to be no evidence of bias in selection of papers for inclusion in the meeting but there is bias in the subsequent publication, which favours positive reports.", "Many abstracts submitted to annual scientific meetings never come to full publication in peer-reviewed journals. The objective of this study was to determine factors associated with the fate of endoscopic research abstracts submitted to the annual scientific meeting of the American Society for Gastrointestinal Endoscopy (ASGE).\n All abstracts (n = 461) submitted to the annual meeting of the ASGE in May of 1994 were retrospectively reviewed. The following databases were searched for evidence of publication of abstracts in full-manuscript form: Medline, HealthSTAR, Current Contents, CINHAL, and Cancerlit. All abstracts were reviewed between May 4, 1998 and June 30, 1998. Univariate and multivariate analysis were performed to determine the association between abstract characteristics and acceptance for presentation at the meeting and for publication.\n Fifty-five percent (247/451) of submitted abstracts were accepted for presentation. In univariate analysis, pediatric studies, prospective studies, randomized studies, and studies from university-affiliated medical centers (UAMC), were more likely to be accepted for presentation (p < 0.05). In multivariate analysis, the variables: pediatric studies (p = 0.01), prospective studies (p = 0.005), randomized studies (p = 0.06), and studies from UAMC (p = 0.01) predicted acceptance of abstracts for presentation at the meeting. The overall publication rate was 25.1%. The publication rates 1, 2, 3, and 4 years after the meeting were 6.7%, 16.2%, 22.8%, and 25.1%, respectively. Multivariate Cox proportional hazards analysis showed that accepted abstracts (p = 0.0003) studies reporting positive results (p = 0.0015), and studies from outside the United States (p = 0.036) were more likely to be published in manuscript form.\n The overall publication rate of abstracts reporting endoscopic research is 25%, lower than that in any published report from other medical societies. Abstracts from the United States were less likely to be published in full-manuscript form. Although there was no positive outcome bias for acceptance of abstracts for presentation at the meeting, there was bias toward publication of statistically significant results. Further investigations are warranted to determine the variation in the publication of research results according to country of origin and to determine factors that hinder publication of GI endoscopic research in manuscript form.", "To determine the rate of publication of abstracts presented at the 1994 American Society of Health System Pharmacists (ASHP) Mid-year Clinical Meeting and the 1994 American College of Clinical Pharmacists (ACCP) Annual Meeting.\n Abstracts presented at the 1994 ASHP Midyear Clinical Meeting and the 1994 ACCP Annual Meeting were evaluated for subsequent publication as full articles in journals indexed in MEDLINE, International Pharmaceutical Abstracts, and Current Contents.\n Five hundred one abstracts presented at the 1994 ASHP Mid-year Clinical Meeting were evaluated; 55 (11%) of these had been published. Two hundred fifteen abstracts presented at the 1994 ACCP Annual Meeting were evaluated; 71 (33%) of these had been published.\n The publication rates for abstracts presented at ASHP and ACCP meetings were found to be lower than many of those for other medical groups. The presentation of research abstracts at professional meetings is an integral part of the exchange of scientific information; however, many of the presented abstracts are not subsequently published as full research reports. The failure to publish the results of the studies may limit the ability of a reader to judge the validity, reliability, and generalizability of the research. This could affect the use of the findings in clinical practice and in supporting or refuting other research findings.", "nan", "Research projects are frequently presented at national meetings not only to make the data available, but also to further critically evaluate the project. The ultimate goal remains publication of the research. We assessed the publication rate of presentations at 1993-95 annual meetings.\n All presentations at the scientific sessions were searched in the computerized database Melvyl MEDLINE and PubMed. The papers were categorized in 6 broad groups.\n The overall proportion of presentations that were published was 32%. Clinical papers in pediatrics had the highest publication rate, followed by basic science research in laryngology and plastics.\n The publication rate of 32% is lower than the rate at meetings in other fields, reflecting variability in selection criteria for the presentations and quality of abstracts presented. Basic science presentations did not have a greater publication rate as compared to clinical presentations.", "Substantial numbers of clinical trials continue to be reported only in summary reports that present insufficient methodological details to permit informed judgments about the likely validity of the conclusions. Using a cohort of 176 controlled trials reported in summary form, we tested the hypotheses that they would be more likely to be followed by full reports if, on the basis of the information provided in the summary report, (1) the trial was judged to be methodologically sound, (2) the results favored the test treatment, and (3) the sample size was relatively large. The results of univariate and multivariate analyses provided support for only the third of these hypotheses. Investigators, as well as those who fund and sanction the conduct of clinical research, should make greater efforts to ensure that clinical trials are reported properly.", "The annual meetings of the Society of Teachers of Family Medicine (STFM) and the North American Primary Care Research Group (NAPCRG) are important peer-reviewed venues for family medicine academicians to present their research. However, a relatively small number of individuals actually hear each presentation. In order to permanently share their research with a large number of peers, these presenters need to take the next step and publish completed manuscripts. This study examined the frequency with which presentations at these meetings are eventually published.\n All abstracts from the 1987 and 1988 meetings of NAPCRG and the PEER and research sections of STFM were followed by performing a Medline computer search for the presenting author. Publications that matched the presentations were identified, and information was recorded about the elapsed time between presentation and publication, and the journal where publication occurred.\n Just under half (48%) of all the presentations were published within 4 or 5 years. There was no difference between 1987 and 1988 presentations, nor between NAPCRG and the combined STFM presentations. However, 69% of STFM research presentations were published compared to 31% of the peer presentations (X2 = 20.6, df = 2, P < .001). The STFM research publications also tended to be in print sooner than other presentations. Fifty-six percent of the publications occurred in family practice journals, with Family Medicine and the Journal of Family Practice being the most common journals.\n Approximately half of the presentations at STFM and NAPCRG annual meeting are published within 4 to 5 years. This is consistent with publication rates found for other specialty meetings. The reasons for not publishing are numerous and need to be better elucidated to help family medicine academicians complete the research loop and disseminate their findings to the scientific community.", "Publication of research results in peer-reviewed journals represents the consummation of the scientific method. In order to determine the rate of publication of oral presentations at the annual meeting of the American Society for Surgery of the Hand, every presentation (n = 397) from the 1990, 1991, and 1992 annual meetings was subjected to a Medline Plus computer search in January 1995. Meeting abstracts were grouped by program designation to scientific session, research session, and residents and fellows conference categories, and a Kaplan-Meier survivorship curve was formulated for each category. We determined an ultimate publication rate of 52% at 53 months. Subanalysis by year of presentation showed rates of 32%, 48%, and 51% for the respective years 1992, 1991, and 1990, with publication for most research occurring within 3 years of presentation. No statistically significant difference existed between the three categories, although a distinct trend toward higher ultimate publication rate (74%) was found for research abstracts. The ultimate publication rate for hand surgery presentations is comparable to that reported for other disciplines.", "Abstract presentations are a valuable means of rapidly conveying new information; however, abstracts that fail to eventually become published are of little use to the general medical community. Our goals were to determine the publication rate of neuroradiologic papers originally presented at national meetings in 1993 and to assess publication rate as a function of neuroradiologic subspecialty and study design.\n Proceedings from the 1993 ASNR and RSNA meetings were reviewed. A MEDLINE search encompassing 1993-1997 was performed cross-referencing lead author and at least one text word based on the abstract title. All ASNR and RSNA neuroradiologic abstracts were included. Study type, subspecialty classification, and sample size were tabulated. Publication rate, based on study design and neuroradiologic subspecialty, was compared with overall publication rate. Median duration from meeting presentation to publication was calculated, and the journals of publication were noted.\n Thirty-seven percent of ASNR abstracts and 33% of RSNA neuroradiologic abstracts were published as articles in indexed medical journals. Publication rates among neuroradiologic subspecialty types were not significantly different. Prospective studies presented at the ASNR were published at a higher rate than were retrospective studies. There was no difference between the publication rate of experimental versus clinical studies. Neuroradiologic abstracts were published less frequently than were abstracts within other medical specialties. Median time between abstract presentation and publication was 15 months.\n Approximately one third of neuroradiologic abstracts presented at national meetings in 1993 were published in indexed journals. This rate is lower than that of abstracts from medical specialties other than radiology.", "The purpose of this study was to determine what factors influence the final publication status of cytopathology studies presented at national meetings. Abstracts involving cytopathology material were obtained from the following journals: Modern Pathology (volume 11, 1998), Acta Cytologica (volume 42, 1998), and the American Journal of Clinical Pathology (volumes 109 and 110, 1998). Using the National Library of Medicine Website, each abstract was searched by author and topic to determine if the study was published as a peer-reviewed article. The following parameters were evaluated: meeting where the abstract was presented, type of institution where the research was based, type of material used in the study, and application of ancillary techniques used in the study. The subsequent published articles were evaluated for journal and time to publication. Out of 257 studies presented in 1998, 85 (33%) were published in peer-reviewed journals by May 2000. The majority of papers were published in Diagnostic Cytopathology (n = 21), Acta Cytologica (n = 15), and Cancer (n = 18). The mean time for publication was 12.8 mo. The highest percentage of published studies was presented at the United States and Canadian Academy of Pathology (USCAP) meeting (50% of presented abstracts), followed by American Society of Cytopathology (ASC) (28%) and American Society of Clinical Pathologists (ASCP) (17%) meetings. Ancillary techniques were applied in 40 of 85 (47%) published studies, 27 of 85 (32%) articles focused on morphology, and 18 of 85 (21%) papers covered other topics (e.g., quality assurance (QA), cost, and role of cytology). In nonpublished studies (n = 172), special techniques were the main focus in 40%, morphology in 25%, and other topics in 35% of abstracts. The great majority (97%) of published studies were from academic institutions. Gynecological and nongynecological material were roughly equally covered in published and nonpublished studies. Only a relatively small percentage of presented studies was finalized in the form of peer-reviewed articles. Type of material and application of ancillary techniques do not significantly influence the outcome.\n Copyright 2001 Wiley-Liss, Inc.", "Studies with positive results are more likely to be published in biomedical journals than are studies with negative results. However, many studies submitted for consideration at scientific meetings are never published in full; bias in this setting is poorly studied.\n To identify features associated with the fate of research abstracts submitted to a scientific meeting.\n Prospective observational cohort, with 5-year follow-up of all research submitted for consideration to the major annual 1991 US research meeting in the specialty of emergency medicine.\n All research abstracts submitted for consideration at the meeting for possible presentation.\n Characteristics associated with acceptance for presentation at the meeting and subsequent publication as a full manuscript.\n A total of 492 research abstracts were submitted from programs in emergency medicine and other specialties affiliated with 103 US medical schools. A total of 179 (36%) were accepted for presentation and 214 (43%) were published in 44 journals. Of the 179 abstracts accepted for presentation, 111 studies were published. Scientific quality of abstracts or prestige of the journal in which the study was eventually published did not predict either of these outcomes. The best predictors (by logistic regression) of meeting acceptance were a subjective \"originality\" factor (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.13-3.89) and positive results (OR, 1.99; 95% CI, 1.07-3.84), and, for publication, meeting acceptance (OR, 2.49; 95% CI, 1.49-4.35) and large sample size (OR, 2.26; 95% CI, 1.23-4.31). Forty-nine percent (241) of abstracts did not report on blinding, and 24% (118) did not report on randomization. Acceptance and publication were both more likely for positive outcomes (P=.03). Funnel plots showed the classic distribution of positive-outcome (\"publication\") bias at each of the submission, acceptance, and publication phases. Meeting acceptance predicted publication with a sensitivity of only 51%, specificity of 71%, positive predictive value of 57%, and negative predictive value of 66%.\n Positive-outcome bias was evident when studies were submitted for consideration and was amplified in the selection of abstracts for both presentation and publication, neither of which was strongly related to study design or quality.", "A computerized search of 276 randomly selected cardiology abstracts published in conjunction with three national meetings revealed that 137 abstracts (49.6 per cent) led to full-length articles in peer-reviewed journals within a period of 37 to 43 months. The median interval between publication of the abstract and of the article was 14 months. Full-length articles were derived from 5. per cent of the abstracts presented at the meetings of the American Federation for Clinical Research, the American Society for Clinical Investigation, and the Association of American Physicians (\"clinical societies\"); 55 per cent of the abstracts presented at the American Heart Association Scientific Sessions; 49 per cent of the abstracts presented at the American College of Cardiology Scientific Sessions; and 35 per cent of the abstracts submitted to the clinical societies but not presented. During the observation period, each abstract was cited a mean of 1.6 times in a journal reference list; the number of citations was not significantly higher for abstracts that led to articles than for abstracts that did not. These findings emphasize the preliminary nature of abstracts and suggest restraint in their citation as references.", "At present the \"Impact Factor\" developed by the Scientific Information Institute (Philadelphia), is an indicator of the quality of the journals in terms of the quality of the papers which are published. The results of odontological research which are presented and discussed at the annual meetings of the DAAIIO are proof of the quality and quantity of scientific production in this area in Argentina. Presentations are undoubtedly numerous. However, their diffusion and qualitative evaluation are of utmost importance. One way to estimate these parameters would be to monitor the ratio between number of presentations and their publication as full papers in journals with a system of referees (Ratio Publ./Pres.). With this aim in mind the presentations at DAAIIO over the 1980-1989 period were considered. Employing the author index of the DAAIIO meetings, we searched for possible publications in the Index Dental and the Index Medicus. The references were compared with the results presented to disregard publications which had not been previously presented at DAAIIO meetings. The data obtained were grouped according to subject area and Research Center. A total of 747 presentations led to 94 publications, the Publ./Pres. Ratio being 1/8 (12.5%). The ratio for each research center was the following: Univ. Buenos Aires 1/7; Natl. Univ. La Plata 1/8; Natl. Univ. Córdoba 1/15. The research groups with the highest publication ratios were Dent. Mat., Natl. Univ. La Plata 1/3; Clinical Pathol., Univ. Bs. As. 1/4; Oral Pathol., Univ. Bs. As. 1/4; Physiol. and Pharmacol., Univ. Bs. As. 1/4; Natl. Univ. Córdoba 1/7. The majority of the publications within 2 years of presentation were in English (69%). These results suggest that an acceptable number of presentations are published, particularly in the area of basic research. We should hope for an increase in the publication/presentation ratio in the future, particularly in the area of applied clinical research since publication would imply technical-scientific quality evaluation of the work by the experts who condition publication.", "What percent of abstracts presented at the American Academy of Orthopaedic Surgeons annual meeting are submitted, survive peer review, and eventually are published? The answer to this fundamental question is important because many national meeting attendees use the unscrutinized information that is presented to alter their surgical practices. At the 1993 American Academy of Orthopaedic Surgeons meeting, 573 abstracts were presented. After a 5-year period, 44% of abstracts presented were published as papers in a peer reviewed journal. The results suggest that for various reasons, the majority of presented material at the Academy meeting has not been authenticated scientifically to be as accurate as papers that survive the rigors of peer review.", "Systematic reviews should identify all relevant trials in order to minimize the potential for bias and the play of chance in their results. Other specialities have shown that conference proceedings are a rich source of trials, but many of these trials are never fully published.\n All clinical trials presented at a single conference (Vth World Congress of Psychiatry, Mexico, 1971) were identified by hand searching. Full publications of these abstracts were then sought on five databases by searching for the authors or relevant key words.\n Full publications were found for 46% of the abstracts. The odds of publication decreased for abstracts that were from a non-Anglophone country or that failed to mention randomization.\n Anyone wishing to undertake a systematic review of a mental-health care topic should search relevant conference proceedings for trials.", "nan", "To analyze the publication in MEDLINE-indexed journals of articles derived from free presentations at the Twentieth Congress of the Spanish Society of Anesthesiology (SEDAR) (Anestesia 92) held in 1992.\n Two of the authors independently investigated the publication of research presented at Anestesia 92 in MEDLINE-indexed journals, carrying out a search of authors' names between 1990 and 1998 with no restrictions on language or type of publication. We obtained year of publication and names of journals and extracted the abstracts, then analyzing the number and order of authors, content and time elapsing between the congress and publication.\n Eighty-four articles (17.1%) were published based on 491 congress presentations, with a mean time to publication of 1.8 years (range -2 to 6). Journals specializing in anesthesiology published 79.8%, and Revista Espanola de Anestesiología y Reanimación published 59.5%. Different authors were listed for published articles and congress presentations in 92.9% and the first author had changed in 35.7%. The content of a published article was similar to that of the congress presentation in 46% and scope was reduced for publication in 35.7%.\n Few publications were derived from free presentations at Anestesia 92 and major changes were made in authors and content between congress presentation and publication.", "To obtain an objective appraisal of the scientific value of abstracts of scientific meetings published in the Dutch Journal of Medicine (Nederlands Tijdschrift voor Geneeskunde; NTvG).\n Retrospective.\n Editorial office of the NTvG.\n A search in MEDLINE was conducted for articles about research presented in 803 abstracts of 54 meetings (29 scientific associations), which appeared in the NTvG in 1988 and January 1989. Scientific associations were assigned to 4 groups (surgery, medicine, non-clinical medicine and a remaining group).\n The overall publication percentage was 48 (385 articles out of 803 presentations). Pathology abstracts showed a significantly higher percentage (65%; p < 0.01), rehabilitation and dermatology abstracts a significantly lower percentage than the overall value (6%; p < 0.00001, 27% respectively; p < 0.04). The larger part of the abstracts was published in the first 2 years after the scientific meeting.\n The scientific relevance of abstracts presented at Dutch scientific meetings is reasonably high, considering the publication percentage. A more rigorous selection by the scientific associations could improve the quality of the abstracts.", "To assess the publication rate of full papers presented as abstracts at the 1995 meeting of the European Society of Anaesthesiologists, and to assess factors that might predict subsequent full publication.\n All abstracts presented at the meeting and published in the British Journal of Anaesthesia (Suppl 1, 1995) were included. To verify subsequent full publication, a MEDLINE search was performed and validated. We studied the average time from the meeting to publication, the first author's country, the subspeciality, the publishing journal of the full report, the type of presentation (oral or poster), the object of investigation, and the quality of research design and of statistical reporting in the abstract.\n Of 472 meeting abstracts, 199 (42.2%) were eventually published. The average (+/- SD) delay between meeting and publication was 16.8 (15.6) months (range 24-60 months). Most papers (79.4%) had been published within 3 yr of the meeting. Circulation, pharmacology and intensive care papers had the highest rates of publication. Sixty-three journals attracted papers, with the British Journal of Anaesthesia publishing most (n = 29). No difference in subsequent publication was found between oral and poster presentations. Randomized trials and animal research were more likely to be published. The number of authors or their positions differed between the abstract and the full publication in 145 cases (72.9%); the first author was changed in 43 cases.\n Less than half of the abstracts accepted at the 1995 European Society of Anesthesiologists' meeting were subsequently published in journals indexed by MEDLINE in the 3 yr following the meeting. Many changes in authorship occurred between the abstract and the full publication. The study architecture and the object of investigation predicted full publication.", "Publication bias toward studies that favor new therapies has been known to occur for the past 40 years, yet its implications are not well studied in child health. The increased interest in meta-analyses has highlighted the need to identify the totality of evidence when addressing treatment questions.\n To measure the percentage of randomized controlled trials (RCTs) presented at a major pediatric scientific meeting that were subsequently published as full-length articles, to investigate factors associated with publication, and to describe the variables that change from abstract to manuscript form.\n The scientific proceedings from the Society for Pediatric Research were hand searched for RCTs (1992-1995). Subsequent publication was ascertained through a search of various electronic databases. Quality of abstracts and manuscripts was measured, and data were extracted using a structured form.\n A total of 264 (59.1%) of 447 abstracts were subsequently published. Almost 64% of RCTs that were subsequently published favored new therapy compared with 43.5% of studies that were never published (P<.001). Mean effect size for published vs unpublished RCTs was 0.74 vs 0.05 (P<.001). Median sample size was larger in published (n = 45) vs unpublished (n = 34) RCTs (P =.02). Quality was significantly lower for abstracts vs published RCTs (P<.001). For 5% of abstracts that were subsequently published, the conclusion regarding treatment efficacy changed.\n Publication bias is a serious threat to assessing the effectiveness of interventions in child health, as little more than half of RCTs presented at a major scientific meeting are subsequently published. There is a need to institute an international registry of RCTs in children so that the totality of evidence can be accessed when assessing treatment effectiveness.", "Research presented to a scientific meeting is inaccessible to clinicians, unless it is also published in a cited journal.\n To assess the publication rate of studies presented to two UK national paediatric meetings: the Paediatric Research Society (PRS) and the British Paediatric Association (BPA).\n A Medline search in December 1999 for the first authors of all plenary abstracts presented in 1996. If not found, authors contacted by postal questionnaire.\n Information was obtained on 88/89 presentations. Twenty five of 48 PRS and 31 of 40 BPA studies were published in Medline listed journals. The major reason for non-publication was that they had not been submitted (PRS 15/48, BPA 6/40). Some authors were still hoping to do so (PRS 7, BPA 2). Other reasons were: publication in other forms (theses, book chapters, non-Medline journals) (PRS 5, BPA 2), or still being reviewed (PRS 3, BPA 1). Ten of 11 randomised, controlled trials were published, but only 20 of 37 observational studies were submitted and published.\n Presenters to paediatric meetings need help in submitting and publishing their work.", "Although the timely conveyance of information at national meetings like those of the Orthopaedic Research Society is critical to the dissemination of new scientific research, the ultimate goal of most researchers is to publish work in peer-reviewed journals referenced in Medline. All of the abstracts that were presented at the podium at the 1991, 1992, and 1993 annual meetings of the Orthopaedic Research Society and printed in the appropriate yearly transactions were included in this study (n=888,296 per year). A detailed computerized Medline search of each author on the abstract and the appropriate keywords from the title was performed until a publication was found; otherwise, the abstract was excluded. The database was searched through June 30, 1997. A total of 463 (52%) of the abstracts were published by July 1, 1997. The percentages for each individual year were similar: 148 (50%) were published in 1991, 162 (55%) in 1992, and 153 (52%) in 1993. Publication of the majority of these papers (93.1%, 431 of 463) occurred within 4 years of the respective meeting. The Journal of Orthopaedic Research published the majority of these papers (17.5%), followed by The Journal of Bone and Joint Surgery (American), the Journal of Biomechanics, Clinical Orthopaedics and Related Research, and Spine (each 5.2%). No significant differences in the rate of publication were observed between papers of 10 broad subject categories (p=0.103). These results are similar to those from other basic science meetings and to the recently reported results for the annual meeting of the American Academy of Orthopaedic Surgeons.", "Abstract Failure to identify all relevant reports of controlled trials is a potential source of bias in systematic reviews of health-care interventions. The present study aims to identify how many reports of trials -initially published as conference abstracts in the Australian and New Zealand Journal of Medicine were subsequently published in full. We identified trial reports by handsearching conference abstracts published in the Journal from 1980 to 2000. We then searched the Cochrane Controlled Trials Register and PubMed to determine how many of these had been subsequently published in full. A total of 962 reports of controlled trials was identified from the conference proceedings of 17 medical societies. Of these, 589 (61%) reports of trials were subsequently published in full, and on average within 1-2 years. Handsearching conference abstracts identified a large number of reports of controlled trials, over one-third of which were unpublished and therefore not easily accessible.", "The purpose of this study was to review abstracts accepted for presentation at the annual national meeting of the Society for Adolescent Medicine (SAM) over the past 3 decades for subject content and research design.\n Retrospective review was conducted of research abstracts for 3 years, selected at random, for the 1990s and then matched at 10-year intervals for the previous 2 decades. The major categories for subject content were: medical, psychosocial, health services, and miscellaneous; for research design categories were: retrospective, observational, experimental, and miscellaneous. Subsequent publication was also assessed.\n The most notable change over the 3 decades in subject content was a shift from medical topics (58% to 19%) to psychosocial topics [20% to 52% (p < .001)] of abstracts, the latter largely accounted for by increases in topics pertaining to high-risk behaviors. There was a substantial decrease in abstracts concerning medical aspects of chronic illness (p < .001), well-adolescent care, growth and development, and psychosocial aspects of chronic illness (p < .02). Regarding research design, the proportion of retrospective studies decreased over the 3 decades (p < .02); the most prevalent design was observational, with an increase in studies using established databases (p < .02). Less than 15% represented an experimental design. Studies using qualitative analysis appeared for the first time in the 1990s. The percentage of presentations which eventuated in published reports increased from 35% to 63% over the 3 decades (p < .02).\n A significant shift occurred in subject content of scientific abstracts from a medical to a psychosocial emphasis. The proportion of retrospective designs decreased, and qualitative analyses emerged. The likelihood of later publication of the studies increased.", "The aim of the study was to investigate the proportion of publications arising from work presented at a regional surgical meeting.\n A list of all presentations to the Welsh Surgical Society 1983-95 was compiled and a detailed search made of the Medicine Database. The surgical topic of each presentation, the date of presentation, the date of publication and the journal of publication were recorded.\n University Hospital of Wales.\n Four hundred and ninety-six papers were presented to the society, of which 402 (81%) were by trainees. The most frequent topics of presentation were colorectal (15%), vascular (15%) and hepato-pancreatico-biliary (11%). Two hundred and thirty-three papers (47%) have been published in peer-reviewed journals. The most popular journals for publication were Annals of the Royal College of Surgeons of England (19%), British Journal of Surgery (16%) and Journal of the Royal College of Surgeons of Edinburgh (8%). The median time from presentation to publication was 17.0 months (interquartile range 10.0-27.5 months).\n Regional surgical meetings have an important role in the annual surgical calendar and they are the ideal initial setting for presentation by trainees.", "The aim of this study was to determine the publication rate of scientific papers in peer review journals presented at the Otorhinolarygological Research Society (ORS) meetings from 1978 to 1995 inclusive. The abstracts of the presentations at ORS meetings are published in Clinical Otolaryngology. A MEDLINE search was performed on abstracts presented at ORS meetings from 1978 to 1995 using both authors and key words within the text of the abstract. The publication rate, journal of publication, time to publication, change in contents, change in authors and change in conclusions of abstracts were tabulated. The publication rate for papers presented at ORS meetings from 1978 to 1995 was 69.09%. The average time to publication was 22.5 months. Papers derived from the ORS abstracts were most commonly published in Clinical Otolaryngology (34%) and Journal of Laryngology and Otology (18.64%). The results indicate that nearly 69% of presented material at the biannual ORS meetings eventually get published in peer reviewed journals. This compares favourably with publication rate of other specialities.", "To determine 1) what proportion of abstracts of randomized controlled trials (RCTs) presented at international conferences on cystic fibrosis (CF) are published as full reports, 2) time to publication, and 3) factors that might delay or prevent publication.\n At the end of 1995, the Cochrane CF Group's register of RCTs contained 199 abstracts describing 180 RCTs. Abstracts were identified by handsearching 44 abstract books of three international CF conferences over a 30-year period. We searched the register for subsequent full reports of these RCTs and used survival analysis to investigate time to publication. Using the log-rank test, we examined 1) whether there is a difference in time to publication between reports where the investigators concluded that the test treatment was as effective as or better than the control treatment, and reports where it was not, and 2) whether there is a difference in time to publication according to sample size.\n Thirty-two percent of the 178 abstracts analyzed were subsequently published in full. Survival analysis indicated that the proportions published before 12 months, 2 years, and 5 years were 8.1%, 29%, and 40% respectively. No difference in time to publication was identified when the abstracts were stratified according to conclusions or sample size; no significant association (P > 0.05) existed between time to publication and both sample size and conclusions together.\n Only a small proportion of abstracts of RCTs presented at international conferences on CF are followed by full publication, and usually only after several years. Therefore, many potentially valuable studies do not reach a wide audience. However, we found no consistent factors which might delay or prevent publication.", "Publication rates and determinants of publication were studied based on abstracts presented at pancreatic meetings. All abstracts presented at the 1994 and 1995 annual meetings of the European Pancreatic Club (EPC) and the American Pancreatic Association (APA) were followed up by searching MEDLINE. Publication rates were compared using log-rank tests and multiple logistic regression. The prestige of the publishing journals was compared using Kruskal-Wallis tests on scientific impact factors (SIF). Overall, 340 abstracts were presented at the EPC, and 254 were presented at the APA. Of these, 203 (59.7%, EPC) and 138 (54.3%, APA) were later published in peer-reviewed journals. Publication rates did not differ by study type or country region of origin. In addition, median SIFs were similar by conference (APA vs. EPC) and research type (basic science vs. clinical studies) (overall, 1.7). However, North American and North/West European articles were published in higher impact journals as compared with those from other countries. Publication rates and median journal SIFs in pancreas research are similar to those reported from other medical specialty meetings. There is no difference by conference, type of research, or origin (North American vs. European).", "nan", "nan", "One measure of the quality of research presented at the annual scientific meeting is publication of the data presented in a peer review journal. This allows for a more rigorous review of design, methodology and conclusions. To determine the rate of subsequent publication, MEDLARS searches were performed on the 269 presented abstracts at the 1984 and 1986 meetings of the American Association of Poison Control Centers, The American Academy of Clinical Toxicology, The American Board of Medical Toxicology and the Canadian Association of Poison Control Centers. Of the 296 presented abstracts, 134 (49.8%) were published. There was no difference in the eventual publication rate between the 1984 and 1986 meeting. There were 38 non-reviewed symposia publications and 96 peer-reviewed articles. Publications of 35.7% of presented abstracts in peer review journals compares poorly with the percentage of peer-reviewed publication from other scientific meetings. If publication in a peer-review journal is important, steps should be taken to improve the percentage of presented abstracts that are accepted by peer-review journals.", "Accessibility of research done locally to clinicians remains limited unless it is in the published form. The publication rate of research presentations at the Annual Malaysian Paediatric Association, Perinatal Society of Malaysia and Academy of Medicine Malaysia in 1997 and 1998 was determined. One hundred and five (95.5%) of 110 research presentations were carried out in Malaysia. Thirty-seven (35.2%) presentations were published. University-affiliated institutions were more likely to publish their research presentations as compared to Ministry of Health hospitals (OR 3.1 95% CI 1.4-6.8, p < 0.01). There is a need to encourage publication of local research presentations. University-affiliated institutions performed better due to institution pressure for career advancement.", "IADR/AADR abstracts of research projects to be presented at the Annual Meeting are published each year in the Journal of Dental Research. An assumption often made is that the material in these abstracts is subsequently published as journal articles. The validity of this assumption was assessed in this study. Following a review of the literature to establish study criteria, the specific objectives of this study were to determine: (1) the percentage of IADR/AADR abstracts subsequently published as articles, (2) the length of time from abstract to publication, and (3) the amount of discrepancy between abstract and article. Ten percent of the IADR/AADR abstracts from the years 1983 (n = 125) and 1984 (n = 150) were randomly selected and surveyed for their publication history. Major reference sources were checked for determination of whether articles had resulted from the abstracts. Of the 1983-1984 abstracts surveyed, the results indicated that more abstracts were not published (78.5% in 1983/76.0% in 1984) than were published (21.6% in 1983/24.0% in 1984). Of those articles previously published as abstracts, the greatest number (44.4% in 1983 47.2% in 1984) were published within ten to 21 months following presentation. The greatest amount of discrepancy between the abstract and the article involved names and numbers of authors, titles, purpose statements, and results/conclusions. In other health disciplines, the percentage of abstracts subsequently published as articles ranged from 31.1% to 53.9%. Since a smaller percentage of the IADR/AADR abstracts surveyed in this study were ultimately published (21.6% to 24%). IADR/AADR should consider various strategies to improve the quality of abstracts and their accessibility.", "To determine the publication rate of abstracts as peer-reviewed manuscripts during the five years subsequent to their presentation, the rates of publication of abstracts that were presented at meetings of four anaesthesia societies (American Society of Anesthesiologists (ASA), International Anesthesia Research Society (IARS), Anaesthesia Research Society (ARS) and Canadian Anaesthetists' Society (CAS), in 1985 were determined. Abstracts (total = 215) from each of the four meetings were selected (ASA n = 114/573 total, IARS n = 39/119, ARS n = 33/99 and CAS n = 29/58) and their appearances in the literature as peer-reviewed manuscripts were determined using MEDLINE for the years 1985 to 1990 under the surname of the presenting author. The contents of the abstracts were compared with those of the resultant manuscripts. The proportions of abstracts from each of the four societies that were published as manuscripts were compared. We found that the mean proportion of abstracts from all four societies that were published as manuscripts within three years of presentation was 44% and within five years 50%. The proportions of abstracts that were published as manuscripts from the four societies were similar. Of the abstracts that were published as manuscripts, 13% from the ASA, 16% from the IARS, 16% from the ARS and 0% from the CAS were published four or five years after abstract presentation. Although the overall proportion of abstracts that was published within five years of presentation did not differ from the rate of publication within three years, we recommend that a uniform policy with respect to the time interval for citation of abstracts be adopted for all anaesthesia journals.", "Research abstracts are frequently referenced in orthopaedic textbooks and influence orthopaedic care. However, little is known about the quality of information provided in the abstracts, the frequency of publication of complete papers after presentation of abstracts, or any discrepancies between abstracts and published papers. The objective of this study was to determine the quality of information provided in orthopaedic abstracts, rates of publication of full-text articles after presentation of abstracts, predictors of publication of full-text articles, and consistency between abstracts and full-text articles.\n We retrieved all abstracts from the 1996 scientific program of the sixty-third Annual Meeting of the American Academy of Orthopaedic Surgeons. For each abstract, we recorded the completeness of reporting and key features of the study design, conduct, analysis, and interpretation. A computerized Medline and PubMed search established whether the abstract had been followed by publication of a full-text article. Finally, we evaluated the consistency of reporting between abstracts and final publications.\n The program included 465 abstracts, 66% of which were on prognostic studies. All abstracts described the study design, and 70.7% of the designs were observational. Key methodological issues were reported in less than half of the abstracts, and information on data analysis was reported in <15%. One hundred and fifty-nine (34%) of the 465 abstracts were followed by publication of a full-text article. The mean time to publication (and standard deviation) was 17.6 +/- 12 months (range, one to fifty-six months). Inconsistencies between the abstract and the full-text article included the primary outcome measure, which differed 14% of the time, and the results, which differed 19% of the time.\n Two-thirds of the orthopaedic abstracts in this sample were not followed by publication of a full-text paper. The overall quality of reporting in abstracts proved inadequate, and inconsistencies between the final published paper and the original abstract occurred frequently. The routine use of abstracts as a guide to orthopaedic practice needs to be reconsidered.", "The aim of this study was to examine the determinants of publication and whether publication bias occurred in gastroenterological research.\n A random sample of abstracts submitted to DDW, the major GI meeting (1992-1995) was evaluated. The publication status was determined by database searches, complemented by a mailed survey to abstract authors. Determinants of publication were examined by Cox proportional hazards model and multiple logistic regression.\n The sample included abstracts on 326 controlled clinical trials (CCT), 336 other clinical research reports (OCR), and 174 basic science studies (BSS). 392 abstracts (47%) were published as full papers. Acceptance for presentation at the meeting was a strong predictor of subsequent publication for all research types (overall, 54% vs. 34%, OR 2.3, 95% CI 1.7 to 3.1). In the multivariate analysis, multi-center status was found to predict publication (OR 2.8, 95% CI 1.6-4.9). There was no significant association between direction of study results and subsequent publication. Studies were less likely to be published in high impact journals if the results were not statistically significant (OR 0.5, 95 CI 95% 0.3-0.6). The author survey identified lack of time or interest as the main reason for failure to publish.\n Abstracts which were selected for presentation at the DDW are more likely to be followed by full publications. The statistical significance of the study results was not found to be a predictor of publication but influences the chances for high impact publication.", "Meetings are an important way of exchanging scientific information, but full diffusion of new information can only be achieved when results are published in scientific journals.\n (1) To determine the publication frequency of accepted abstracts for the yearly international conferences on pharmacoepidemiology (ICPE) and to examine predicting variables; (2) if published, to determine impact differences between 'oral' and 'poster' abstracts and to determine type and nature of publishing journals.\n Abstracts accepted for ICPE 1995-1999, published in the official conference supplement of Pharmacoepidemiology and Drug Safety, were included. Publication status for the information contained in each abstract was evaluated through MEDLINE and IPA searches. Impact factors of publishing journals were retrieved and journals were included in one of five groups.\n Overall, one out of three abstracts resulted in a publication in the peer-reviewed journals studied. Abstracts from North America were more often presented orally than abstracts from Europe, but had lower publication chances. 'Oral' abstracts were more likely to be published than 'poster' abstracts; abstracts with a strong methodological content had a lower publication frequency. Most of the published abstracts were found in pharmacology and pharmacy journals (33%) and journals on specific clinical topics (30%).\n Only one out of three papers presented at ICPE ends up in established peer-reviewed journals. Although the publication characteristics for ICPE are not very different from other conferences, there are certain questions that warrant further investigation.", "Publication in a peer-reviewed journal is the ultimate lasting acknowledgment of an author's research results. Numerous clinical and basic-science papers are presented at the Annual Meeting of The American Academy of Orthopaedic Surgeons, but not all of these presentations culminate in publication in a peer-reviewed journal. In an effort to determine the percentages and patterns of publication, every presentation from the 1990, 1991, and 1992 meetings (a total of 1465 presentations) was reviewed with use of a Melvyl Medline Plus computer search during the summer of 1996. The presentations were classified on the basis of subspecialty. The over-all rate of publication by August 1996 was 46 per cent (668 of 1465), and the rates were similar for the 1990, 1991, and 1992 meetings. The average time to publication was twenty months, and most publications appeared within three years after presentation, with a plateau thereafter. Basic-science presentations had the highest rate of publication: 64 per cent (eighteen of twenty-eight presentations). The rates of publication by clinical subspecialty ranged from 39 per cent (twenty-eight of seventy-two presentations in the hand subspecialty and eighty-two of 210 presentations in the trauma subspecialty) to 53 per cent (110 of 206 presentations in the spine subspecialty). There was no significant difference among these groups (p = 0.611, chi-square test). The American volume of The Journal of Bone and Joint Surgery published the most papers (24 per cent; 161 of the 668 publications), followed by Clinical Orthopaedics and Related Research (16 per cent; 106 of 668). The over-all rate of publication of presentations at the Annual Meeting of The American Academy of Orthopaedic Surgeons is comparable with reported rates in other medical specialties.", "Of 55 abstracts presented at the 1979 annual meeting of the International Anesthesia Research Society (I.A.R.S.) 24 (43.6%) and of 62 abstracts presented at the 1980 annual meeting of the I.A.R.S. 25 (40.3%) were published by July 1, 1981. Of 324 abstracts presented at the 1978 annual meeting of the American Society of Anesthesiologists (A.S.A.) 98 papers (30.1%) were published by January 1, 1981. Eighty-two percent of the I.A.R.S. meeting papers and 66.7% of the A.S.A. papers were published in anesthesia journals, and the rest of the papers appeared in publications representing a variety of other disciplines. The average lag time between publication of the abstract and publication as an article was 8.2 months for I.A.R.S. abstracts and 12.2 months for A.S.A. abstracts. By July 1, 1981, four 1979 I.A.R.S. abstracts were filed in Science Citation Index (SCI) as cited reference and by January 1, 1981, fifty-six 1979 A.S.A. abstracts were filed.", "Large clinical trials are the criterion standard for making treatment decisions, and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions.\n To determine the rate of full publication of large randomized trials presented at annual meetings of the American Society of Clinical Oncology (ASCO), quantify bias against publishing nonsignificant results, and identify factors associated with time to publication.\n Survey of 510 abstracts from large (sample size, > or =200), phase 3, randomized controlled trials presented at ASCO meetings between 1989 and 1998. Trial results were classified as significant (P< or =.05 for the primary outcome measure) or nonsignificant (P>.05 or not reported), and the type of presentation and sponsorship were identified. Subsequent full publication was identified using a search of MEDLINE and EMBASE, completed November 1, 2001; the search was updated in November 2002, using the Cochrane Register of Controlled Trials. Authors were contacted if the searches did not find evidence of publication.\n Publication rate at 5 years; time from presentation to full publication.\n Of 510 randomized trials, 26% were not published in full within 5 years after presentation at the meeting. Eighty-one percent of the studies with significant results had been published by this time compared with 68% of the studies with nonsignificant results (P<.001). Studies with oral or plenary presentation were published sooner than those not presented (P =.002), and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified (P =.02). These factors remained significant in a multivariable model. The most frequent reason cited by authors for not publishing was lack of time, funds, or other resources.\n A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation. Bias against publishing nonsignificant results is a problem even for large randomized trials. Nonpublication breaks the contract that investigators make with trial participants, funding agencies, and ethics boards.", "A review of all the presentations at three major spine specialty meetings held over a 3-year period.\n To determine the rate of publication in peer-reviewed journals after presentations at major spine meetings conducted annually by the following three organizations: North American Spine Society (NASS), Scoliosis Research Society (SRS), and International Society for the Study of the Lumbar Spine (ISSLS).\n The rate of publication for presentations at national and international meetings has been determined for medical and surgical subspecialties. This rate has been used to judge the quality of the content of the meetings and to determine the validity of the research presentations.\n All presentations either in poster or oral presentation form were entered into a database covering a 3-year period for spine specialty meetings conducted annually by the following three organizations: NASS 1990 to 1992, SRS 1991 to 1993, and ISSLS 1991 to 1993. A computer search for each abstract was performed with the Melvyl Medline Plus database to determine if the abstract had been published in a peer-reviewed journal from 1990 to the end of 1997. Publication rates for presentations at these three meetings were determined over a 3-year period.\n A total of 1186 abstracts were listed over a 3-year period in the final programs of these three meetings for the years 1991 to 1993 (SRS, ISSLS) and 1990 to 1992 (NASS). Of these 1186 abstracts, 516 were published in peer-reviewed journals, giving an overall publication rate of 43.5%. The publication rates for the three different meetings (NASS, SRS, ISSLS) were similar, with values of 40%, 47%, and 45% respectively. More than 90% of the publications resulting from these meetings were published within a period of 4 years from the data of the meeting.\n The publication rates of presentations at three major spine specialty meetings are high and quite comparable with the publication rates of meetings in other medical subspecialties. This reflects the high quality of the meeting programs and validates their selection process.", "The adequacy of research presented in abstract form for presentation at scientific meetings remains a concern, as indicated by the proportion of such research appearing in scientific journals after peer review. This report examines the publication of research presented at the pediatrics meetings and the effect of a change in selection procedure for abstracts presented at the Ambulatory Pediatric Association meetings for the years 1979 and 1980. Throughout the period, about half of the presentations were published, usually in general pediatric journals, with an average time to publication of about 20 months. The change in selection procedure resulted in little change in the proportion published among either presentations or abstracts submitted but not selected for presentation, but it did lead to a reduction in time to publication. This experience suggests a mechanism for enhancing the timeliness of publication of research presented at scientific meetings without adversely affecting the process of selection.", "nan", "nan", "The aims of the present study were to determine the publication rate of abstracts presented by Australasian emergency physicians at major emergency medicine meetings and to identify the site of publication of papers.\n All free paper abstracts presented (oral and poster) by Australasian emergency physicians and trainees at five Australasian College for Emergency Medicine/Australasian Society for Emergency Medicine and International Conference on Emergency Medicine meetings between 1995 and 1998 were identified retrospectively from conference programmes. In order to determine whether or not the abstract had been published, the PubMed database (http://www4.ncbi.nlm.nih.gov/PubMed/) was searched using the presenter's name and key words from the abstract. In addition, a hand search of the non-abstracted journal Emergency Medicine was conducted.\n Of the 207 free paper abstracts identified, 73 (35%) had been published as full articles. Papers were published in a variety of journals; however, Emergency Medicine accounted for almost half the published papers. The mean time between presentation and publication was 12.6 months (median 11 months).\n The abstract to publication rate for papers presented by Australasian emergency physicians and trainees at Australasian College for Emergency Medicine/Australasian Society for Emergency Medicine and International Conference on Emergency Medicine meetings is 35%, which is lower than that reported by some other established specialities, but comparable to rates reported for US-based national and international emergency medicine meetings. Future research should look at barriers to the publication of findings and ways to assist the publication process.", "Our aim was to determine the fate of mandatory resident research projects with regard to subsequent presentation and publication.\n In this retrospective descriptive study required research projects were assessed for frequency of presentation at regional and national meetings or publication in medical journals, or both, over a 10-year period (1983 through 1992). Rising second-year house officers elected to initiate their own study with departmental support under the guidance of a faculty advisor or selected a research project from a list of potential investigations offered by departmental faculty. Projects were presented at the annual alumni meeting in April of the junior and senior years. The faculty advisor assisted in research design, protocol development, obtaining human investigation committee approval, data collection, statistical analysis, manuscript preparation, and coaching for the oral presentation. After local presentation these projects were evaluated for submission to regional and national meetings and prepared for peer-review publication.\n During a 10-year period 104 resident research projects resulted in 72 regional or national presentations and 52 peer-review publications. There was a significant increase in the proportion of projects presented at national meetings over time (r = 0.99; p < 0.0001). There was also an increase in the number of projects published in peer-review journals during the decade-long study period (r = 0.96, p = 0.0001).\n Required completion of two research studies during residency bolstered by early selection of prospective projects and departmental fiscal support, as well as intensive faculty advisor direction and assistance, has resulted in resident projects with increasingly frequent national recognition.", "To evaluate the publication rate of abstracts presented during the German Anaesthesia Congress (DAK) in MEDLINE-listed journals in comparison to the publication rate of abstracts presented during the meeting of the European Society of Anaesthesiologists (ESA).\n All abstracts of free papers (FP, orals) and posters of the 1994 DAK and the 1994 ESA meeting were included. Over a period of approximately 7 years (1993 to May 1999) the appearance of authors and abstracts topics in the literature were searched with the help of MEDLINE. Only original papers were included in the analysis.\n All 322 abstracts (268 FPs and 54 posters) of the DAK and all 244 abstracts (81 FP and 163 posters) of the ESA were analyzed. A total 122 of the DAK abstracts (37.9% of all abstracts) and 111 of the ESA abstracts (45.5% of all abstracts) were published in MEDLINE-listed journals. Posters presented at the DAK were as published often (37%) as were oral presentations (38%). Of the 122 abstracts of the DAK that were published 71 (58.2%) were published in English (in 38 different journals) and 51 (41.8%) were published in German (in 8 different journals), whereas 102 (92%) of the ESA abstracts were published in english (in 42 different journals).\n The overall portion of abstracts of the DAK published in MEDLINE indexed journals within 7 years was disappointing. The reasons for this may include deliberate avoidance of a publication (e.g. due to lack of interest to publish, no time) or low quality of the abstract that hinders publication in a MEDLINE indexed journal.", "A computerized MEDLINE search was performed to determine the publication pattern of the abstracts submitted for podium presentation at the 1991-1994 annual meetings of the Pediatric Orthopaedic Society of North America (POSNA). The publication percentage for all papers submitted to the POSNA meetings from 1991 through 1994 was 45%. Fifty-three percent of papers accepted for podium presentation were ultimately published in comparison with 38% of those not accepted for presentation (p < 0.001). The mean time to publication was 29 months and did not differ significantly for the two groups. The majority of papers (65%) were published in either Journal of Pediatric Orthopaedics (48%) or The Journal of Bone and Joint Surgery (American) (17%). The frequency of ultimate publication of abstracts submitted to the annual POSNA meetings compares favorably with the rates for other medical subspecialties.", "Randomized controlled trials (RCTs) are accepted as the gold standard for assessing the effectiveness of clinical interventions but are rarely reported in pediatric surgery. Have RCTs submitted to the British Association of Paediatric Surgeons (BAPS) Annual Congress during the last 5 years been adequately designed and large enough to produce a valid result?\n Abstracts accepted by the Annual BAPS Congress meetings between 1996 and 2000 were examined in collaboration with a senior health services researcher. The quality of the design, methodology, statistical analysis and conclusions, and the adequacy of the sample size were assessed for all identifiable clinical RCTs.\n From 760 accepted abstracts, there were only 9 RCTs (1%) of clinical interventions. In only 4 trials was the relevant primary end-point specified at the outset of the study, and none documented the method of randomization. Only one abstract mentioned blinding with respect to the intervention or outcome measure. Sample sizes were inadequate to detect even large clinical differences. To date, only one of these RCTs has been published in an English-language, peer-reviewed journal.\n Clear guidelines exist for the conduct of RCTs, yet compliance with these standards was rarely documented in abstracts of pediatric surgical RCTs presented at BAPS. Sample sizes were inadequate. RCTs in pediatric surgery are difficult to perform, but the specialty would benefit from well-designed, carefully conducted, multicentre, clinical RCTs to advance evidence-based practice.\n Copyright 2003, Elsevier Science (USA). All rights reserved.", "To determine the publication rate of the scientific papers presented at the Orthopaedic Trauma Association (OTA) meetings from 1990 to 1995 inclusive.\n A Medline search was performed on abstracts presented at the OTA sessions from 1990 through 1995 using both authors and key text words within the OTA abstract. The publication rate for each meeting, journal of publication, and time to publication were tabulated.\n The publication rate for papers presented at the OTA meetings from 1990 through 1994 was 64 percent. This was significantly better than publication rates reported for American Academy of Orthopaedic Surgeons (AAOS) meetings in 1990 through 1992. The average time to publication was sixteen months. The most common journals in which papers derived from the OTA abstracts were published include the Journal of Orthopaedic Trauma (JOT), Journal of Bone and Joint Surgery combined volumes (JBJS). and Clinical Orthopaedics and Related Research (CORR).\n OTA meetings are an excellent source of high-quality information, which is generally subsequently published in peer-reviewed journals. The Journal of Orthopaedic Trauma is the single best source for information presented at the OTA meetings. Allowing more papers to be presented did not affect the publication rate for the meetings.", "This retrospective review of the 1990 ABA orally presented abstracts found an overall publication rate of slightly more than 26%. This included both same-content and related-content publications. When the abstracts were made a subset by theme, a major variance in the publication rates was found. Abstracts that had a psychologic content (72.73%), for example, fared much better than reports of in vitro research (6.9%). This overall rate when compared to publication studies in other clinical areas was found to be quite low. This study further found that there was a great deal of similarity between abstracts that were published and those that were not. The one meaningful predictor of ultimate journal publication was the clarity of the presentation of statistically related information." ]

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[ "A controlled trial of psychodynamic psychotherapy for co-occurring borderline personality disorder and alcohol use disorder.", "Interpersonal outcome of cognitive behavioral treatment for chronically suicidal borderline patients.", "Systems Training for Emotional Predictability and Problem Solving (STEPPS) for outpatients with borderline personality disorder: a randomized controlled trial and 1-year follow-up.", "Outpatient psychotherapy for borderline personality disorder: randomized trial of schema-focused therapy vs transference-focused psychotherapy.", "Hunter DBT project: randomized controlled trial of dialectical behaviour therapy in women with borderline personality disorder.", "Implementation of outpatient schema therapy for borderline personality disorder with versus without crisis support by the therapist outside office hours: A randomized trial.", "Preliminary data on an acceptance-based emotion regulation group intervention for deliberate self-harm among women with borderline personality disorder.", "Cognitive-behavioral treatment of chronically parasuicidal borderline patients.", "Randomized controlled trial of outpatient mentalization-based treatment versus structured clinical management for borderline personality disorder.", "Effectiveness of partial hospitalization in the treatment of borderline personality disorder: a randomized controlled trial.", "Combined treatment of major depression in patients with borderline personality disorder: a comparison with pharmacotherapy.", "Combined therapy of major depression with concomitant borderline personality disorder: comparison of interpersonal and cognitive psychotherapy.", "Cognitive therapy versus Rogerian supportive therapy in borderline personality disorder. Two-year follow-up of a controlled pilot study.", "Transference-focused psychotherapy v. treatment by community psychotherapists for borderline personality disorder: randomised controlled trial.", "A pilot study of Manual-Assisted Cognitive Therapy with a Therapeutic Assessment augmentation for Borderline Personality Disorder.", "The effectiveness of cognitive behavior therapy for borderline personality disorder: results from the borderline personality disorder study of cognitive therapy (BOSCOT) trial.", "A schema-focused approach to group psychotherapy for outpatients with borderline personality disorder: a randomized controlled trial.", "A randomized trial of dialectical behavior therapy versus general psychiatric management for borderline personality disorder.", "Two-year randomized controlled trial and follow-up of dialectical behavior therapy vs therapy by experts for suicidal behaviors and borderline personality disorder.", "Manual assisted cognitive treatment for deliberate self-harm in borderline personality disorder patients.", "A preliminary, randomized trial of psychoeducation for women with borderline personality disorder.", "Dialectical behaviour therapy skills training compared to standard group therapy in borderline personality disorder: a 3-month randomised controlled clinical trial.", "Adaptation of interpersonal psychotherapy to borderline personality disorder: a comparison of combined therapy and single pharmacotherapy.", "Sustained efficacy of dialectical behaviour therapy for borderline personality disorder.", "A randomized controlled trial of a Dutch version of systems training for emotional predictability and problem solving for borderline personality disorder." ]

[ "A randomized controlled trial was conducted to determine whether a manual-based psychodynamic treatment, labeled dynamic deconstructive psychotherapy (DDP), would be feasible and effective for individuals with co-occurring borderline personality disorder (BPD) and alcohol use disorder. Thirty participants were assessed every 3 months during a year of treatment with either DDP or treatment as usual (TAU) in the community. DDP participants showed statistically significant improvement in parasuicide behavior, alcohol misuse, institutional care, depression, dissociation, and core symptoms of BPD, and treatment retention was 67% to 73%. Although TAU participants received higher average treatment intensity, they showed only limited change during the same period. The results support the feasibility, tolerability, and efficacy of DDP for the co-occurring subgroup and highlight the need for further research. (PsycINFO Database Record (c) 2010 APA, all rights reserved).", "This study reports the efficacy of a cognitive behavioral outpatient treatment on interpersonal outcome variables for patients diagnosed with borderline personality disorder.\n In a 1-year clinical trial, 26 female patients with borderline personality disorder were randomly assigned to either dialectical behavior therapy or a treatment-as-usual comparison condition. All subjects met criteria of DSM-III-R and Diagnostic Interview for Borderline Patients for borderline personality disorder and were chronically suicidal.\n In both the intent-to-treat and treatment completion groups, dialectical behavior therapy subjects had significantly better scores on measures of anger, interviewer-rated global social adjustment, and the Global Assessment Scale and tended to rate themselves better on overall social adjustment than treatment-as-usual subjects.\n These results suggest that dialectical behavior therapy is a promising psychosocial intervention for improving interpersonal functioning among severely dysfunctional patients with borderline personality disorder.", "Systems Training for Emotional Predictability and Problem Solving (STEPPS) is a 20-week manual-based group treatment program for outpatients with borderline personality disorder that combines cognitive behavioral elements and skills training with a systems component. The authors compared STEPPS plus treatment as usual with treatment as usual alone in a randomized controlled trial.\n Subjects with borderline personality disorder were randomly assigned to STEPPS plus treatment as usual or treatment as usual alone. Total score on the Zanarini Rating Scale for Borderline Personality Disorder was the primary outcome measure. Secondary outcomes included measures of global functioning, depression, impulsivity, and social functioning; suicide attempts and self-harm acts; and crisis utilization. Subjects were followed 1 year posttreatment. A linear mixed-effects model was used in the analysis.\n Data pertaining to 124 subjects (STEPPS plus treatment as usual [N=65]; treatment as usual alone [N=59]) were analyzed. Subjects assigned to STEPPS plus treatment as usual experienced greater improvement in the Zanarini Rating Scale for Borderline Personality Disorder total score and subscales assessing affective, cognitive, interpersonal, and impulsive domains. STEPPS plus treatment as usual also led to greater improvements in impulsivity, negative affectivity, mood, and global functioning. These differences yielded moderate to large effect sizes. There were no differences between groups for suicide attempts, self-harm acts, or hospitalizations. Most gains attributed to STEPPS were maintained during follow-up. Fewer STEPPS plus treatment as usual subjects had emergency department visits during treatment and follow-up. The discontinuation rate was high in both groups.\n STEPPS, an adjunctive group treatment, can deliver clinically meaningful improvements in borderline personality disorder-related symptoms and behaviors, enhance global functioning, and relieve depression.", "Borderline personality disorder is a severe and chronic psychiatric condition, prevalent throughout health care settings. Only limited effects of current treatments have been documented.\n To compare the effectiveness of schema-focused therapy (SFT) and psychodynamically based transference-focused psychotherapy (TFP) in patients with borderline personality disorder.\n A multicenter, randomized, 2-group design.\n Four general community mental health centers.\n Eighty-eight patients with a Borderline Personality Disorder Severity Index, fourth version, score greater than a predetermined cutoff score.\n Three years of either SFT or TFP with sessions twice a week.\n Borderline Personality Disorder Severity Index, fourth version, score; quality of life; general psychopathologic dysfunction; and measures of SFT/TFP personality concepts. Patient assessments were made before randomization and then every 3 months for 3 years.\n Data on 44 SFT patients and 42 TFP patients were available. The sociodemographic and clinical characteristics of the groups were similar at baseline. Survival analyses revealed a higher dropout risk for TFP patients than for SFT patients (P = .01). Using an intention-to-treat approach, statistically and clinically significant improvements were found for both treatments on all measures after 1-, 2-, and 3-year treatment periods. After 3 years of treatment, survival analyses demonstrated that significantly more SFT patients recovered (relative risk = 2.18; P = .04) or showed reliable clinical improvement (relative risk = 2.33; P = .009) on the Borderline Personality Disorder Severity Index, fourth version. Robust analysis of covariance (ANCOVA) showed that they also improved more in general psychopathologic dysfunction and measures of SFT/TFP personality concepts (P<.001). Finally, SFT patients showed greater increases in quality of life than TFP patients (robust ANCOVAs, P=.03 and P<.001).\n Three years of SFT or TFP proved to be effective in reducing borderline personality disorder-specific and general psychopathologic dysfunction and measures of SFT/TFP concepts and in improving quality of life; SFT is more effective than TFP for all measures.", "Deliberate self-harm (DSH), general hospital admission and psychiatric hospital admission are common in women meeting criteria for borderline personality disorder (BPD). Dialectical behaviour therapy (DBT) has been reported to be effective in reducing DSH and hospitalization.\n A randomized controlled trial of 73 female subjects meeting criteria for BPD was carried out with intention-to-treat analyses and per-protocol analyses. The intervention was DBT and the control condition was treatment as usual plus waiting list for DBT (TAU+WL), with outcomes measured after 6 months. Primary outcomes were differences in proportions and event rates of: any DSH; general hospital admission for DSH and any psychiatric admission; and mean difference in length of stay for any hospitalization. Secondary outcomes were disability and quality of life measures.\n Both groups showed a reduction in DSH and hospitalizations, but there were no significant differences in DSH, hospital admissions or length of stay in hospital between groups. Disability (days spent in bed) and quality of life (Physical, Psychological and Environmental domains) were significantly improved for the DBT group.\n DBT produced non-significant reductions in DSH and hospitalization when compared to the TAU+WL control, due in part to the lower than expected rates of hospitalization in the control condition. Nevertheless, DBT showed significant benefits for the secondary outcomes of improved disability and quality of life scores, a clinically useful result that is also in keeping with the theoretical constructs of the benefits of DBT.", "This study aimed to evaluate the success of implementing outpatient schema focused therapy (ST) for borderline patients in regular mental healthcare and to determine the added value of therapist telephone availability outside office hours in case of crisis (TTA).\n To enhance the implementation, the following adaptations regarding the original ST protocol were applied: a reduction in the frequency and duration of the therapy; training therapists of eight regular healthcare centers in ST with a structured and piloted program supported by a set of films (DVDs) with examples of ST techniques; training and supervision given by Dutch experts. Telephone availability outside office hours was randomly allocated to 50% of the therapists of each treatment center. Patient's outcome measures were assessed with a semi-structured interview and self-report measures on BPD, quality of life, general psychopathology and an ST questionnaire, before, during and after treatment.\n Data on 62 DSM-IV defined BPD patients were available. Intention-to-treat analyses showed that after 1.5 years of ST 42% of the patients had recovered from BPD. No added value of therapist telephone availability (TTA) was found on the BPDSI score nor on any other measure after 1.5 years of ST.\n ST for BPD can be successfully implemented in regular mental healthcare. Treatment results and dropout were comparable to a previous clinical trail. No additional effect of extra crisis support with TTA outside office hours ST was found.", "Borderline personality disorder (BPD) and deliberate self-harm are clinically important conditions for which additional economically and clinically feasible interventions are needed. Literature on both the emotion regulating and experientially avoidant function of self-harm and the role of emotional dysfunction in BPD provided the rationale for developing a group intervention targeting emotion dysregulation among self-harming women with BPD. This study provides preliminary data on the efficacy of this new, 14-week, emotion regulation group intervention, designed to teach self-harming women with BPD more adaptive ways of responding to their emotions so as to reduce the frequency of their self-harm behavior. Participants were matched on level of emotion dysregulation and lifetime frequency of self-harm and randomly assigned to receive this group in addition to their current outpatient therapy (N = 12), or to continue with their current outpatient therapy alone for 14 weeks (N = 10). Results indicate that the group intervention had positive effects on self-harm, emotion dysregulation, experiential avoidance, and BPD-specific symptoms, as well as symptoms of depression, anxiety, and stress. Participants in the group treatment condition evidenced significant changes over time on all measures, and reached normative levels of functioning on most. While these preliminary results are promising, the study's limitations require their replication in a larger-scale randomized controlled trial.", "A randomized clinical trial was conducted to evaluate the effectiveness of a cognitive-behavioral therapy, ie, dialectical behavior therapy, for the treatment of chronically parasuicidal women who met criteria for borderline personality disorder. The treatment lasted 1 year, with assessment every 4 months. The control condition was \"treatment as usual\" in the community. At most assessment points and during the entire year, the subjects who received dialectical behavior therapy had fewer incidences of parasuicide and less medically severe parasuicides, were more likely to stay in individual therapy, and had fewer inpatient psychiatric days. There were no between-group differences on measures of depression, hopelessness, suicide ideation, or reasons for living although scores on all four measures decreased throughout the year.", "This randomized controlled trial tested the effectiveness of an 18-month mentalization-based treatment (MBT) approach in an outpatient context against a structured clinical management (SCM) outpatient approach for treatment of borderline personality disorder.\n Patients (N=134) consecutively referred to a specialist personality disorder treatment center and meeting selection criteria were randomly allocated to MBT or SCM. Eleven mental health professionals equal in years of experience and training served as therapists. Independent evaluators blind to treatment allocation conducted assessments every 6 months. The primary outcome was the occurrence of crisis events, a composite of suicidal and severe self-injurious behaviors and hospitalization. Secondary outcomes included social and interpersonal functioning and self-reported symptoms. Outcome measures, assessed at 6-month intervals, were analyzed using mixed effects logistic regressions for binary data, Poisson regression models for count data, and mixed effects linear growth curve models for self-report variables.\n Substantial improvements were observed in both conditions across all outcome variables. Patients randomly assigned to MBT showed a steeper decline of both self-reported and clinically significant problems, including suicide attempts and hospitalization.\n Structured treatments improve outcomes for individuals with borderline personality disorder. A focus on specific psychological processes brings additional benefits to structured clinical support. Mentalization-based treatment is relatively undemanding in terms of training so it may be useful for implementation into general mental health services. Further evaluations by independent research groups are now required.", "This study compared the effectiveness of psychoanalytically oriented partial hospitalization with standard psychiatric care for patients with borderline personality disorder.\n Thirty-eight patients with borderline personality disorder, diagnosed according to standardized criteria, were allocated either to a partially hospitalized group or to a standard psychiatric care (control) group in a randomized controlled design. Treatment, which included individual and group psychoanalytic psychotherapy, was for a maximum of 18 months. Outcome measures included the frequency of suicide attempts and acts of self-harm, the number and duration of inpatient admissions, the use of psychotropic medication, and self-report measures of depression, anxiety, general symptom distress, interpersonal function, and social adjustment. Data analysis used repeated measures analysis of covariance and nonparametric tests of trend.\n Patients who were partially hospitalized showed a statistically significant decrease on all measures in contrast to the control group, which showed limited change or deterioration over the same period. An improvement in depressive symptoms, a decrease in suicidal and self-mutilatory acts, reduced inpatient days, and better social and interpersonal function began at 6 months and continued until the end of treatment at 18 months.\n Psychoanalytically oriented partial hospitalization is superior to standard psychiatric care for patients with borderline personality disorder. Replication is needed with larger groups, but these results suggest that partial hospitalization may offer an alternative to inpatient treatment.", "Combined treatment with psychotherapy and antidepressants is more effective than monotherapies. Recent data show that combined therapy has better results in patients with depression and Axis II codiagnosis. The aim of this study was to compare combined treatment using interpersonal psychotherapy (IPT) with pharmacotherapy alone in patients with depression and borderline personality disorder (BPD).\n There were 39 consecutive outpatients diagnosed with BPD who presented with a major depressive episode enrolled in this study. They were randomly assigned to 1 of 2 treatment groups: fluoxetine 20 mg to 40 mg daily or fluoxetine 20 mg to 40 mg daily plus IPT 1 session weekly. Owing to noncompliance, 7 patients dropped out. We assessed the 32 patients who completed the 24 weeks of treatment at baseline, Week 12, and Week 24, using a semistructured interview for clinical characteristics, the Clinical Global Impression Scale (CGI), the Hamilton Depression Rating Scale (HDRS), and the Hamilton Anxiety Rating Scale (HARS), and 2 self-report questionnaires, that is, the Satisfaction Profile (SAT-P) for quality of life and the 64-item Inventory for Interpersonal Problems (IIP-64). We performed statistical analysis, using univariate general linear models with 2 factors: duration and type of treatment.\n Changes in remission rates, CGI, and HARS score did not differ between treatments. According to changes in the HDRS scores; changes in psychological functioning and social functioning scores on the SAT-P; and changes in vindictive or self-centred, cold or distant, intrusive or needy, and socially inhibited scores on the IIP-64, combined therapy was superior to fluoxetine alone.\n Combined therapy with IPT is more effective than antidepressant therapy alone, both in treating symptoms of major depression and in improving dimensions of quality of life and interpersonal functioning.", "The combination of antidepressants and brief psychotherapies has been proven more efficacious in treating major depression and is particularly recommended in patients with concomitant personality disorders. We compare the effects of 2 combined therapies, fluoxetine and interpersonal therapy (IPT) or fluoxetine and cognitive therapy (CT), on major depression in patients with borderline personality disorder (BPD).\n Thirty-five consecutive outpatients with a diagnosis of BPD and a major depressive episode (not bipolar and not psychotic) were enrolled. They were randomly assigned to 1 of the 2 combined treatments and treated for 24 weeks. Assessment included a semistructured interview, Clinical Global Impression (CGI) scale, Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Beck Depression Inventory-II (BDI-II), Social and Occupational Functioning Assessment Scale (SOFAS), Satisfaction Profile (SAT-P) for quality of life (QOL), and Inventory of Interpersonal Problems (IIP-64). Statistical analysis was performed using the univariate General Linear Model to calculate the effects of duration and type of treatment.\n No significant differences between treatments were found at CGI, HDRS, BDI-II, and SOFAS score. Combined treatment with CT had greater effects on HARS score and on psychological functioning factor of SAT-P. Combined treatment with IPT was more effective on social functioning factor of SAT-P and on domains domineering or controlling and intrusive or needy of IIP-64.\n Both combined therapies are efficacious in treating major depression in patients with BPD. Differences between CT and IPT concern specific features of subjective QOL and interpersonal problems. These findings lack reliable comparisons and need to be replicated.", "To date, there have been no studies comparing cognitive therapy (CT) with Rogerian supportive therapy (RST) in borderline personality disorder.\n Sixty-five DSM-IV borderline personality disorder outpatients were recruited at 2 centres: Lyon and Marseille. Thirty-three patients were randomly allocated to CT and 32 to RST. The therapists were the same in both groups. Both treatments shared the same duration (1 year) and amount of therapy. Assessment by independent evaluators utilised the Clinical Global Impression (CGI) Scale, the Hamilton Depression Scale, Beck Depression Inventory, Beck Anxiety Inventory, Hopelessness Scale, Young Schema Questionnaire II, Eysenck Impulsivity Venturesomeness Empathy (IVE) Inventory, a self-harming behaviours checklist and scales measuring quality of life and the therapeutic relationship. The response criterion was a score of 3 or less on the CGI, associated with a Hopelessness Scale score of <8.\n No patient committed suicide during the trial. Fifty-one patients were evaluated at week 24, 38 at week 52 and 21 at week 104. Cognitive therapy retained the patients in therapy for a longer time. The response criterion found no significant between-group differences at any measurement point in the completers. However, at week 24, CT was better than RST on the Hopelessness Scale, IVE scale and regarding the therapeutic relationship. At week 104, the CGI improvement (patient and evaluator) was significantly better in CT than in RST. High baseline depression and impulsivity predicted dropouts.\n CT retained the patients in therapy longer, showed earlier positive effects on hopelessness and impulsivity, and demonstrated better long-term outcomes on global measures of improvement.\n Copyright 2009 S. Karger AG, Basel.", "Transference-focused psychotherapy is a manualised treatment for borderline personality disorder.\n To compare transference-focused psychotherapy with treatment by experienced community psychotherapists.\n In a randomised controlled trial (NCT00714311) 104 female out-patients were treated for 1 year with either transference-focused psychotherapy or by an experienced community psychotherapist.\n Significantly fewer participants dropped out of the transference-focused psychotherapy group (38.5% v. 67.3%) and also significantly fewer attempted suicide (d = 0.8, P = 0.009). Transference-focused psychotherapy was significantly superior in the domains of borderline symptomatology (d = 1.6, P = 0.001), psychosocial functioning (d = 1.0, P = 0.002), personality organisation (d = 1.0, P = 0.001) and psychiatric in-patient admissions (d = 0.5, P = 0.001). Both groups improved significantly in the domains of depression and anxiety and the transference-focused psychotherapy group in general psychopathology, all without significant group differences (d = 0.3-0.5). Self-harming behaviour did not change in either group.\n Transference-focused psychotherapy is more efficacious than treatment by experienced community psychotherapists in the domains of borderline symptomatology, psychosocial functioning, and personality organisation. Moreover, there is preliminary evidence for a superiority in the reduction of suicidality and need for psychiatric in-patient treatment.", "This study examined the efficacy of Manual Assisted Cognitive Therapy (MACT) as a stand-alone treatment for Borderline Personality Disorder (BPD) with suicidal ideation, and piloted a Therapeutic Assessment (TA) intervention among 16 patients randomly assigned to MACT or MACT+TA. Although MACT was associated with significant reductions in BPD features and suicidal ideation, less than half of the sample completed the treatment. The TA augmentation did not improve treatment retention but it was associated with somewhat greater clinical improvement. Although findings associate MACT with symptom reduction among persisting patients, attrition rate was problematically high in the overall sample.\n Copyright (c) 2010 Elsevier Ltd. All rights reserved.", "The outcome of a randomized controlled trial of cognitive behavior therapy in addition to treatment as usual (CBT plus TAU) compared with TAU alone (TAU) in one hundred and six participants meeting diagnostic criteria for borderline personality disorder is described. We anticipated that CBT plus TAU would decrease the number of participants with in-patient psychiatric hospitalizations or accident and emergency room contact or suicidal acts over twelve months treatment and twelve months follow-up, compared with TAU. We also anticipated that CBT plus TAU would lead to improvement in a range of secondary outcomes of mental health and social functioning compared to TAU. Of the 106 participants randomized, follow-up data on 102 (96%) was obtained at two years. Those randomized to CBT were offered an average of 27 sessions over 12 months and attended on average 16 (range 0 to 35). We found that the global odds ratio of a participant in the CBT plus TAU group compared with the TAU alone group having any of the outcomes of a suicidal act, in-patient hospitalization, or accident and emergency contact in the 24 months following randomization was 0.86 (95% confidence interval [CI] 0.45 to 1.66, p = 0.66). The corresponding global odds ratio, excluding accident and emergency room contact, was 0.75 (95% CI 0.37 to 1.54, p = 0.44). In terms of the number of suicidal acts, there was a significant reduction over the two years in favor of CBT plus TAU over TAU, with a mean difference of -0.91 (95% CI -1.67 to -0.15, p = 0.020). Across both treatment arms there was gradual and sustained improvement in both primary and secondary outcomes, with evidence of benefit for the addition of CBT on the positive symptom distress index at one year, and on state anxiety, dysfunctional beliefs and the quantity of suicidal acts at two year follow-up. CBT can deliver clinically important changes in relatively few clinical sessions in real clinical settings.", "This study tests the effectiveness of adding an eight-month, thirty-session schema-focused therapy (SFT) group to treatment-as-usual (TAU) individual psychotherapy for borderline personality disorder (BPD). Patients (N=32) were randomly assigned to SFT-TAU and TAU alone. Dropout was 0% SFT, 25% TAU. Significant reductions in BPD symptoms and global severity of psychiatric symptoms, and improved global functioning with large treatment effect sizes were found in the SFT-TAU group. At the end of treatment, 94% of SFT-TAU compared to 16% of TAU no longer met BPD diagnosis criteria (p<.001). This study supports group SFT as an effective treatment for BPD that leads to recovery and improved overall functioning.", "The authors sought to evaluate the clinical efficacy of dialectical behavior therapy compared with general psychiatric management, including a combination of psychodynamically informed therapy and symptom-targeted medication management derived from specific recommendations in APA guidelines for borderline personality disorder.\n This was a single-blind trial in which 180 patients diagnosed with borderline personality disorder who had at least two suicidal or nonsuicidal self-injurious episodes in the past 5 years were randomly assigned to receive 1 year of dialectical behavior therapy or general psychiatric management. The primary outcome measures, assessed at baseline and every 4 months over the treatment period, were frequency and severity of suicidal and nonsuicidal self-harm episodes.\n Both groups showed improvement on the majority of clinical outcome measures after 1 year of treatment, including significant reductions in the frequency and severity of suicidal and nonsuicidal self-injurious episodes and significant improvements in most secondary clinical outcomes. Both groups had a reduction in general health care utilization, including emergency visits and psychiatric hospital days, as well as significant improvements in borderline personality disorder symptoms, symptom distress, depression, anger, and interpersonal functioning. No significant differences across any outcomes were found between groups.\n These results suggest that individuals with borderline personality disorder benefited equally from dialectical behavior therapy and a well-specified treatment delivered by psychiatrists with expertise in the treatment of borderline personality disorder.", "Dialectical behavior therapy (DBT) is a treatment for suicidal behavior and borderline personality disorder with well-documented efficacy.\n To evaluate the hypothesis that unique aspects of DBT are more efficacious compared with treatment offered by non-behavioral psychotherapy experts.\n One-year randomized controlled trial, plus 1 year of posttreatment follow-up.\n University outpatient clinic and community practice.\n One hundred one clinically referred women with recent suicidal and self-injurious behaviors meeting DSM-IV criteria, matched to condition on age, suicide attempt history, negative prognostic indication, and number of lifetime intentional self-injuries and psychiatric hospitalizations.\n One year of DBT or 1 year of community treatment by experts (developed to maximize internal validity by controlling for therapist sex, availability, expertise, allegiance, training and experience, consultation availability, and institutional prestige).\n Trimester assessments of suicidal behaviors, emergency services use, and general psychological functioning. Measures were selected based on previous outcome studies of DBT. Outcome variables were evaluated by blinded assessors.\n Dialectical behavior therapy was associated with better outcomes in the intent-to-treat analysis than community treatment by experts in most target areas during the 2-year treatment and follow-up period. Subjects receiving DBT were half as likely to make a suicide attempt (hazard ratio, 2.66; P = .005), required less hospitalization for suicide ideation (F(1,92) = 7.3; P = .004), and had lower medical risk (F(1,50) = 3.2; P = .04) across all suicide attempts and self-injurious acts combined. Subjects receiving DBT were less likely to drop out of treatment (hazard ratio, 3.2; P < .001) and had fewer psychiatric hospitalizations (F(1,92) = 6.0; P = .007) and psychiatric emergency department visits (F(1,92) = 2.9; P = .04).\n Our findings replicate those of previous studies of DBT and suggest that the effectiveness of DBT cannot reasonably be attributed to general factors associated with expert psychotherapy. Dialectical behavior therapy appears to be uniquely effective in reducing suicide attempts.", "This study examines the efficacy of a short-term individual therapy, Manual Assisted Cognitive Treatment (MACT), which was developed to treat parasuicidal (suicidal or self-harming) patients. In this trial, MACT was modified to focus on deliberate self-harm (DSH) in patients with borderline personality disorder (BPD). Thirty BPD patients who were engaged in DSH while in ongoing treatments, i.e., treatment-as-usual (TAU), were randomly assigned to receive MACT (N = 15) or not. DSH and level of suicide ideation were assessed at the baseline, at completion of the MACT intervention, and six months later. Results indicated that MACT was associated with significantly less frequent DSH upon completion of the intervention and with significantly decreased DSH frequency and severity at the six months follow-up. Moreover, MACT's contribution to reducing DSH frequency and severity was greater than the contribution by the amount of concurrent treatments. In contrast, MACT did not affect the level of suicide ideation and time-to-repeat of DSH. In conclusion, MACT seems to be a promising intervention for DSH in patients with BPD. More definitive studies are needed.", "The main objective of this study was to determine whether being taught the latest information concerning borderline personality disorder (BPD) leads to a decline in core BPD symptoms and an improvement in psychosocial functioning. Fifty-five late adolescent women participated in a rigorous diagnostic assessment and 50 met DIB-R and DSM-IV criteria for BPD. All 50 were informed that they met criteria for BPD. Then 30 were randomized to a psychoeducation workshop that took place within a week of diagnostic disclosure. The other 20 were assigned to a waitlist and participated in the workshop at the end of this 12-week study. The two primary outcome measures were readministered each week of the trial: the Zanarini Rating Scale for DSM-IV Borderline Personality Disorder (ZAN-BPD) and the Sheehan Disability Scale (SDS). Immediate psychoeducation concerning the BPD diagnosis was associated with a significantly greater decline in general impulsivity and the storminess of close relationships. However, it did not result in significantly improved psychosocial functioning. Taken together, the results of this study suggest that informing patients about BPD soon after diagnostic disclosure may help to alleviate the severity of two of the core elements of borderline psychopathology-general impulsivity and unstable relationships. They also suggest that such instruction may prove to be a useful and cost-efficient form of pre-treatment.", "Dialectical behaviour therapy (DBT) has proven to be an effective treatment in borderline personality disorder (BPD). However, the effectiveness in BPD of DBT skills training (DBT-ST) alone is not known. This study aimed at comparing the efficacy of DBT-ST and standard group therapy (SGT) for outpatients with BPD. Sixty patients meeting the DSM-IV diagnostic criteria for BPD, as assessed by two semi-structured diagnostic interviews, were included in a 3-month, single-blind randomised controlled trial. A total of 13 weekly group psychotherapy sessions of 120 min of either SGT or DBT-ST were conducted. Assessments were carried out every 2 weeks by two blinded evaluators. Observer-rater, self-report scales and behavioural reports were used as outcome measures. DBT-ST was associated with lower dropout rates, 34.5% compared to 63.4% with SGT. It was superior to SGT in improving several mood and emotion areas, such as: depression, anxiety, irritability, anger and affect instability. A reduction in general psychiatric symptoms was also observed. Three-months weekly DBT-ST proved useful. This therapy was associated with greater clinical improvements and lower dropout rates than SGT. DBT-ST seems to play a role in the overall improvement of BPD seen with standard DBT intervention. It allows straightforward implementation in a wide range of mental health settings and provides the additional advantage that it is cost effective.", "Combined treatment with interpersonal psychotherapy (IPT) and antidepressants (ADs) has been found more effective than single pharmacotherapy in patients with major depression and concomitant borderline personality disorder (BPD). The aim of our study is to investigate whether combined treatment with a modified version of IPT is still superior to ADs when treating patients with a single diagnosis of BPD.\n Fifty-five consecutive outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, diagnosis of BPD were enrolled. They were randomly assigned to 2 treatment arms for 32 weeks: fluoxetine 20 to 40 mg per day plus clinical management; and fluoxetine 20 to 40 mg per day plus IPT adapted to BPD (IPT-BPD). Eleven patients (20%) discontinued treatment owing to noncompliance. Forty-four patients completed the treatment period. They were assessed at baseline, and at week 16 and 32 with: a semi-structured interview for demographic and clinical variables; Clinical Global Impression Scale (CGI-S); Hamilton Depression Rating Scale (HDRS); Hamilton Anxiety Rating Scale (HARS); Social and Occupational Functioning Assessment Scale (SOFAS); BPD Severity Index (BPD-SI); and a questionnaire for quality of life (Satisfaction Profile [SAT-P]). A univariate general linear model was performed with 2 factors: duration and type of treatment. P values of less than 0.05 were considered significant.\n Remission rates did not differ significantly between subgroups. Duration, but not type of treatment, had a significant effect on CGI-S, HDRS, SOFAS, and total BPD-SI score changes. Combined therapy was more effective on the HARS; the items: interpersonal relationships, affective instability, and impulsivity of BPD-SI; and the factors: psychological functioning and social functioning of SAT-P.\n Combined therapy with adapted IPT was superior to fluoxetine alone in BPD patients, concerning a few core symptoms of the disorder, anxiety, and quality of life.", "Dialectical Behaviour Therapy (DBT) is considered one of the most promising treatments for borderline personality disorder (BPD). Recently, we reported significantly positive effects of 12 months DBT on parasuicidal behaviour and impulsivity in a mixed group of female BPD patients with and without substance abuse. Fifty-eight women with BPD were randomly assigned to either 52 weeks of DBT or treatment as usual (TAU). Follow-up assessment took place at 78 weeks, i.e., 6 months after discontinuation of DBT. Participants were clinical referrals from addiction treatment and psychiatric services. Outcome measures included parasuicidal behaviour, impulsivity and substance abuse. Six months after treatment discontinuation, the benefits of DBT over TAU in terms of lower levels of parasuicidal and impulsive behaviours, and in alcohol use, sustained. No differences between the treatment conditions were found for drug abuse. In conclusion, DBT seems to have a sustained effect on some of the core symptoms of BPD and on alcohol problems in a mixed population of female borderline patients with and without substance abuse problems.", "Systems Training for Emotional Predictability and Problem Solving (STEPPS) is a group treatment for persons with borderline personality disorder (BPD) that is relatively easy to implement. We investigated the efficacy of a Dutch version of this treatment (VERS). Seventy-nine DSM-IV BPD patients were randomly assigned to STEPPS plus an adjunctive individual therapy, or to treatment as usual. Assessments took place before and after the intervention, and at a 6-month follow-up. STEPPS recipients showed a significantly greater reduction in general psychiatric and BPD-specific symptomatology than subjects assigned to treatment as usual; these differences remained significant at follow-up. STEPPS also led to greater improvement in quality of life, especially at follow-up. No differences in impulsive or parasuicidal behavior were observed. Effect sizes for the differences between the treatments were moderate to large. The results suggest that the brief STEPPS program combined with limited individual therapy can improve BPD-treatment in a number of ways." ]

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[ "Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients.", "A placebo controlled clinical trial of buprenorphine as a treatment for opioid dependence.", "A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence.", "Buprenorphine versus methadone in the treatment of opioid-dependent cocaine users.", "Comparison of buprenorphine and methadone in the treatment of opioid dependence.", "Methadone versus buprenorphine maintenance for the treatment of heroin-dependent outpatients.", "Controlled, randomized trial in maintenance treatment of intravenous buprenorphine dependence with naltrexone, methadone or buprenorphine: a novel study.", "A placebo-controlled study of high dose buprenorphine in opiate dependents waiting for medication-assisted rehabilitation in Oslo, Norway.", "Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial.", "A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence.", "Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.", "Randomized clinical trial to compare the effects of methadone and buprenorphine on the immune system in drug abusers.", "Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse.", "A controlled trial of buprenorphine treatment for opioid dependence.", "Implementing buprenorphine treatment in community settings in Australia: experiences from the Buprenorphine Implementation Trial.", "Buprenorphine: a controlled clinical trial in the treatment of opioid dependence.", "Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone.", "1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial.", "Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence.", "Buprenorphine versus methadone maintenance for the treatment of opioid dependence.", "Double-blind randomized trial of buprenorphine and methadone in opiate dependence.", "A controlled trial of buprenorphine treatment for opium dependence: the first experience from Iran.", "Buprenorphine versus methadone maintenance for opioid dependence.", "Twelve-month maintenance treatment of opium-dependent patients." ]

[ "To assess the efficacy of buprenorphine compared with methadone maintenance therapy for opioid dependence in a large sample using a flexible dosing regime and the marketed buprenorphine tablet.\n Patients were randomized to receive buprenorphine or methadone over a 13-week treatment period in a double-blind, double-dummy trial.\n Three methadone clinics in Australia.\n Four hundred and five opioid-dependent patients seeking treatment.\n Patients received buprenorphine or methadone as indicated clinically using a flexible dosage regime. During weeks 1-6, patients were dosed daily. From weeks 7-13, buprenorphine patients received double their week 6 dose on alternate days.\n Retention in treatment, and illicit opioid use as determined by urinalysis. Self-reported drug use, psychological functioning, HIV-risk behaviour, general health and subjective ratings were secondary outcomes.\n Intention-to-treat analyses revealed no significant difference in completion rates at 13 weeks. Methadone was superior to buprenorphine in time to termination over the 13-week period (Wald chi 2 = 4.371, df = 1, P = 0.037), but not separately for the single-day or alternate-day dosing phases. There were no significant between-group differences in morphine-positive urines, or in self-reported heroin or other illicit drug use. The majority (85%) of the buprenorphine patients transferred to alternate-day dosing were maintained in alternate-day dosing.\n Buprenorphine did not differ from methadone in its ability to suppress heroin use, but retained approximately 10% fewer patients. This poorer retention was due possibly to too-slow induction onto buprenorphine. For the majority of patients, buprenorphine can be administered on alternate days.", "Large-scale placebo controlled clinical trials assessing the efficacy of medications for the treatment of drug dependence have generally been limited to alcohol, cocaine and nicotine dependent populations. The purpose of the present study was to assess the early (1-2 week) clinical effectiveness of buprenorphine versus placebo in an opioid dependent population. The study used a parallel-group design with a behavioral choice component to compare buprenorphine (a mu-opioid partial agonist) to placebo for the treatment of opioid dependence. Opioid dependent volunteer patients participated in a 14-day study to assess the effectiveness and patient acceptance of this new pharmacotherapy for the treatment of opioid dependence. Patients were randomly assigned to placebo (n = 60) or 2 mg (n = 60) or 8 mg (n = 30) daily sublingual buprenorphine. All doses were administered double-blind. On days 6-13 all patients could request a dose change, knowing that their new dose would be randomly chosen from the remaining 2 alternatives. Compared to placebo, patients given buprenorphine (independent of dose) showed greater time on initial dose, requested fewer dose changes, used less illicit opioids (assessed by urinalysis), and rated dose adequacy higher. These results demonstrate that a placebo controlled study with a behavioral choice component is an effective means of assessing the potential efficacy and acceptability of new pharmacotherapies for opioid dependence.", "Opioid dependence is a chronic, relapsing disorder with important public health implications.\n In a 17-week randomized study of 220 patients, we compared levomethadyl acetate (75 to 115 mg), buprenorphine (16 to 32 mg), and high-dose (60 to 100 mg) and low-dose (20 mg) methadone as treatments for opioid dependence. Levomethadyl acetate and buprenorphine were administered three times a week. Methadone was administered daily. Doses were individualized except in the group assigned to low-dose methadone. Patients with poor responses to treatment were switched to methadone.\n There were 55 patients in each group; 51 percent completed the trial. The mean (+/-SE) number of days that a patient remained in the study was significantly higher for those receiving levomethadyl acetate (89+/-6), buprenorphine (96+/-4), and high-dose methadone (105+/-4) than for those receiving low-dose methadone (70+/-4, P<0.001). Continued participation was also significantly more frequent among patients receiving high-dose methadone than among those receiving levomethadyl acetate (P=0.02). The percentage of patients with 12 or more consecutive opioid-negative urine specimens was 36 percent in the levomethadyl acetate group, 26 percent in the buprenorphine group, 28 percent in the high-dose methadone group, and 8 percent in the low-dose methadone group (P=0.005). At the time of their last report, patients reported on a scale of 0 to 100 that their drug problem had a mean severity of 35 with levomethadyl acetate, 34 with buprenorphine, 38 with high-dose methadone, and 53 with low-dose methadone (P=0.002).\n As compared with low-dose methadone, levomethadyl acetate, buprenorphine, and high-dose methadone substantially reduce the use of illicit opioids.", "This study compared the efficacy of buprenorphine to methadone for decreasing cocaine use in patients with combined opioid and cocaine use. Participants (n = 51) were enrolled in a 26-week treatment program and randomly assigned to either buprenorphine or methadone. Dosing was double-blind and double-dummy. Patients were stabilized on either 8 mg sublingual buprenorphine or 50 mg oral methadone, with dose increases given in response to continued illicit cocaine use or opioid use through week 16 of treatment. Maximum doses possible were 16 mg buprenorphine and 90 mg methadone. Average doses achieved were 11.2 mg buprenorphine and 66.6 mg methadone; 49% of the patients received the maximum doses possible. Urine samples were collected three times per week, and there was no significant difference in the rate of cocaine positive urines for the intent-to-treat sample (69% for buprenorphine versus 63% for methadone). For patients who remained in treatment through the flexible dosing period (n = 28), there were significant decreases in cocaine positive urines over time (P < 0.01), but no significant differences between groups or group x time effects. Buprenorphine and methadone were equally effective on measures of treatment retention, urine results for opioids, and compliance with attendance and counseling. These results demonstrate no selective efficacy of either buprenorphine or methadone in attenuating cocaine use in this population, but do provide further support for the equivalent efficacy of buprenorphine and methadone in the treatment of opioid dependence.", "This study compared the efficacy of buprenorphine and methadone in the treatment of opioid dependence.\n Participants (N = 164) were relatively treatment-naive, opioid-dependent applicants to a 26-week treatment program who were randomly assigned to either methadone or buprenorphine treatment. Dosing was double-blind and double-dummy. Patients were stabilized on a regimen of either methadone, 50 mg, or buprenorphine, 8 mg, with dose changes possible through week 16 of treatment. Urine samples were collected three times a week, and weekly counseling was provided.\n Buprenorphine (mean dose = 8.9 mg/day) and methadone (mean dose = 54 mg/day) were equally effective in sustaining retention in treatment, compliance with medication, and counseling regimens. In both groups, 56% of patients remained in treatment through the 16-week flexible dosing period. Overall opioid-positive urine sample rates were 55% and 47% for buprenorphine and methadone groups, respectively; cocaine-positive urine sample rates were 70% and 58%. Evidence was obtained for the effectiveness of dose increases in suppressing opioid, but not cocaine, use among those who received dose increases.\n The results of this study provide further support for the utility of buprenorphine as a new medication in the treatment of opioid dependence and demonstrate efficacy equivalent to that of methadone when used during a clinically guided flexible dosing procedure.", "The aim of this study was to assess the efficacy of methadone compared with buprenorphine maintenance therapy in heroin-dependent patients over a treatment period of 18 weeks. Subjects were randomized to receive either methadone or buprenorphine in a comparative double-blind study and consisted of 164 heroin-dependent male patients who met the DSM-IV criteria for heroin dependence and were seeking treatment. The 164 subjects included 41 patients in 1-mg, 41 patients in 3-mg, and 41 patients in 8-mg dosage group of buprenorphine, and also 41 patients in the 30-mg dosage group of methadone. The mean age was 31.4 years for total buprenorphine group and 33.7 years for methadone group (the mean age differences in 4 groups were not statistically significant). Subjects received buprenorphine at a dose of 1, 3, or 8 mg per day or methadone at a dose of 30 mg per day and were treated in an urban outpatient clinic, offering a 1-hour weekly individual counseling session. Days retained in treatment were measured. Completion rates by buprenorphine dosage group were 29.3% for the 1-mg dose group, 46.3% for the 3-mg dose group, 68.3% for the 8-mg dose group, and 61% for the 30-mg methadone dose group. Retention in the 8-mg dose group was significantly better than in the 1-mg dose group (p=.00041) and in the 3-mg dose group (p=.045); other comparison (1 mg dose with 3 mg dose) was not significant. Methadone group was significantly better than 1mg buprenorphine dose group (p=.004), but was not significantly different from 3 mg buprenorphine dose group (p=.18) or 8 mg buprenorphine dose group (p=.49). The results support the efficacy of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose (8 mg) of buprenorphine was the best of the three doses of buprenorphine, and also support the superiority of 30 mg of methadone compared to 1 mg dose of buprenorphine for Iranian heroin-dependent patients to increase their retention in treatment.", "To test the effect of a 50-mg day-1 dose of naltrexone in the maintenance treatment of intravenous-buprenorphine dependence in comparison with a 50-mg day-1 dose of methadone and also a 5-mg day-1 dose of buprenorphine over a 24-week treatment period.\n Two hundred and four intravenous-buprenorphine-dependent patients who met the DSM-IV criteria for opioid dependence were randomized to three equal groups and were treated in a clinic in Iran where they were also offered a weekly 0.5-h counselling session, in 2002.\n The mean age was 31.2 years (range 17-53). The majority [63.2%] was between 20 and 34 years of age. The educational level of most of them [55.4%] was between 6 and 12 years of study. Completion rates by groups were 83.8% for the 50-mg dose methadone group, 58.8% for the 5-mg dose buprenorphine group and 20.6% for the 50-mg dose naltrexone group (P = 0.000). Retention in the 50-mg methadone group was significantly better than in the 5-mg dose buprenorphine group (P = 0.001) and the 50-mg dose naltrexone group (P = 0.000). Retention in the 5-mg buprenorphine group was significantly better than in the 50-mg naltrexone dose group (P = 0.000).\n Evaluation of the Iranian experience on this subject may be useful for other countries.", "To evaluate whether buprenorphine. even without additional control and psychosocial treatment and support, alleviates the problems faced by patients waiting for medication assisted rehabilitation (MAR).\n A randomized, double-blind, 12-week study of Subutex versus placebo without additional support as an interim therapy.\n One hundred and six patients, 70 males and 36 females, waiting for MAR in Oslo. The average age was 38 years with an average history of heroin use of 20 years. Fifty-five patients were assigned to buprenorphine and 51 to a placebo.\n Subutex or placebo sublingual tablets were given under supervision in a daily dose of 16 mg with the exception of a double dose on Saturday and no dose on Sunday.\n Retention, compliance, self-reported drug-abuse, wellbeing and mental health.\n The average number of days of participation was significantly higher in the buprenorphine group, 42 (median: 29) compared to 14 (median: 11) for the placebo group (P < 0.001). The retention of patients after 12 weeks was 16 patients in the buprenorphine group and one patient in the placebo group. The buprenorphine group had a larger decrease in reported opioid use (p < 0.001) and in reported use of other drugs, tablets and alcohol abuse (p < 0.01). The group also showed a stronger increase in wellbeing (p < 0.01) and life satisfaction (p < 0.05). None of the participants died.\n The patients waiting for MAR benefited significantly from the buprenorphine as an interim therapy according to retention, self-reported use of drugs and wellbeing. However, the patients had difficulties in remaining in treatment over time without psychosocial support.", "To evaluate the safety and efficacy of an 8 mg/day sublingual dose of buprenorphine in the maintenance treatment of heroin addicts by comparison with a 1 mg/day dose over a 16-week treatment period. As a secondary objective, outcomes were determined concurrently for patients treated with two other dose levels.\n Patients were randomized to four dosage groups and treated double-blind.\n Twelve outpatient opiate maintenance treatment centers throughout the United States.\n Two hundred and thirty-nine women and 497 men who met the DSM-III-R criteria for opioid dependence and were seeking treatment.\n Patients received either 1, 4, 8 or 16 mg/day of buprenorphine and were treated in the usual clinical context, including a 1-hour weekly clinical counseling session.\n Retention in treatment, illicit opioid use as determined by urine toxicology, opioid craving and global ratings by patient and staff. Safety outcome measures were provided by clinical monitoring and by analysis of the reported adverse events.\n Outcomes in the 8 mg group were significantly better than in the 1 mg group in all four efficacy domains. No deaths occurred in either group. The 8 mg group did not show an increase in the frequency of adverse events. Most reported adverse effects were those commonly seen in patients treated with opioids.\n The findings support the safety and efficacy of buprenorphine and suggest that an adequate dose of buprenorphine will be a useful addition to pharmacotherapy.", "Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction. We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance.\n Two hundred twenty-five treatment-seeking opioid addicts (46 women, 179 men) were randomly assigned to receive, in a double-blind manner, either 8 mg/d of buprenorphine, 30 mg/d of methadone, or 80 mg/d of methadone maintenance over a 1-year period. Objective and subjective measures of efficacy (urine toxicology, retention, craving, and withdrawal symptoms) were examined at the study midpoint and at termination, and safety data were tabulated over the entire 52-week study period.\n Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention, opioid use, and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points. Performance on these measures was virtually identical between the latter two groups. No serious adverse health effects attributable to buprenorphine were noted.\n Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study. Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups. There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage.", "Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence.\n This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10.\n In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence.\n Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.", "Buprenorphine may be a useful alternative option to methadone in addicts. Opioids can produce severe changes in the immune system.\n The objectives of this study are to compare the effect of sublingual buprenorphine and methadone on the immune system and to compare the two substances on the drying-out program compliance.\n We studied 62 randomized outpatients for a period of 12 months. Subjects (55 males and 7 females; mean age 25+/-4 years; average history of heroin abuse being 2 years) on maintenance treatment were assigned in two groups (A and B). Methadone chloride (medium dose 100 mg/day) was administered to group A, whereas group B received sublingual buprenorphine (32.40+/-2.8 mg/day). Urine toxicological screening, plasma levels of TNF-alpha interleukin-1, interleukin-beta, lymphocyte CD14 and a self-rating depression questionnaire were measured.\n Urine screening was negative for opiates in 17.6% of group A and in 10.7% of group B (p<0.001; r = 0.62). Depression score was 62+/-2 in group A and 55+/-3 in group B (p < 0.01). Cytokine and CD14 revealed higher concentrations both in groups A and B without significant differences (p > 0.05) between the two groups.\n The effects of buprenorphine and methadone tested on the immune system were overlapping in our patients. The elevated cytokine levels observed may suggest that the two drugs stimulate immunologic hyperactivation of an immune system that was formerly inhibited by heroin. Furthermore, our data suggest that buprenorphine can be a valid alternative to methadone in maintenance treatment of chronic heroin abuse and referred a marked decline in depression.", "Buprenorphine, a partial mu-agonist and kappa-antagonist, has been proposed as an alternative to methadone for maintenance treatment of opioid dependence, especially for patients with concurrent cocaine dependence or abuse. This study evaluated whether higher maintenance doses of buprenorphine and methadone are superior to lower doses for reducing illicit opioid use and whether buprenorphine is superior to methadone for reducing cocaine use.\n A total of 116 subjects were randomly assigned to 1 of 4 maintenance treatment groups involving higher or lower daily doses of sublingual buprenorphine (12 or 4 mg) or methadone (65 or 20 mg) in a double-blind, 24-week clinical trial. Outcome measures included retention in treatment and illicit opioid and cocaine use as determined by urine toxicology testing and self-report.\n There were significant effects of maintenance treatment on rates of illicit opioid use, but no significant differences in treatment retention or the rates of cocaine use. The rates of opioid-positive toxicology tests were lowest for treatment with 65 mg of methadone (45%), followed by 12 mg of buprenorphine (58%), 20 mg of methadone (72%), and 4 mg of buprenorphine (77%), with significant contrasts found between 65 mg of methadone and both lower-dose treatments and between 12 mg of buprenorphine and both lower-dose treatments.\n The results support the superiority of higher daily buprenorphine and methadone maintenance doses vs lower doses for reducing illicit opioid use, but the results do not support the superiority of buprenorphine compared with methadone for reducing cocaine use.", "To assess the efficacy of buprenorphine for short-term maintenance/detoxification.\n A randomized, double-blind, parallel group study comparing buprenorphine, 8 mg/d, methadone, 60 mg/d, and methadone, 20 mg/d, in a 17-week maintenance phase followed by an 8-week detoxification phase.\n Outpatient facilities at the Addiction Research Center, Baltimore, Md.\n One hundred sixty-two volunteers seeking treatment for opioid dependence.\n In addition to the medication, counseling using a relapse prevention model was offered but not required.\n Retention time in treatment, urine samples negative for opioids, and failure to maintain abstinence.\n Throughout the maintenance phase, retention rates were significantly greater for buprenorphine (42%) than for methadone, 20 mg/d (20%, P less than .04); the percentage of urine samples negative for opioids was significantly greater for buprenorphine (53%, P less than .001) and methadone, 60 mg/d (44%, P less than .04), than for methadone, 20 mg/d (29%). Failure to maintain abstinence during the maintenance phase was significantly greater for methadone, 20 mg/d, than for buprenorphine (P less than .03). During the detoxification phase, no differences were observed between groups with respect to urine samples negative for opioids. For the entire 25 weeks, retention rates for buprenorphine (30%, P less than .01) and methadone, 60 mg/d (20%, P less than .05), were significantly greater than for methadone, 20 mg/d (6%). All treatments were well tolerated, with similar profiles of self-reported adverse effects. The percentages of patients who received counseling did not differ between groups.\n Buprenorphine was as effective as methadone, 60 mg/d, and both were superior to methadone, 20 mg/d, in reducing illicit opioid use and maintaining patients in treatment for 25 weeks.", "Buprenorphine was registered in Australia as a maintenance and detoxification agent for the management of opioid dependence in November, 2000, and became widely available in August, 2001. This paper provides an overview of key developments in the introduction of buprenorphine treatment in Australia, with an emphasis upon the delivery of services in community-based (primary care) settings. A central study in this work was the Buprenorphine Implementation Trial (BIT), a randomized, controlled trial comparing buprenorphine and methadone maintenance treatment delivered under naturalistic conditions by specialist and community-based service providers (general practitioners and community pharmacists) in 139 subjects across nineteen treatment sites. In addition to conventional patient outcome measures (treatment retention, drug use, psychosocial functioning, and cost effectiveness), the BIT study also involved the development and evaluation of clinical guidelines, training programs for clinicians, and client literature, which are described here. Integration of treatment systems (methadone with buprenorphine, specialist and primary-care programs) and factors thought to be important in the uptake of buprenorphine treatment in Australia since registration are discussed.", "Clinical trials carried out to compare methadone and buprenorphine in the treatment of opioid dependence have generally employed an alcoholic solution of buprenorphine, which has a bioavailability superior to that of the tablets. Since the product available for large scale use is in tablet form, one intended to verify the efficacy of this formulation. In a multicentre randomised controlled double blind study, 72 opioid dependent patients were assigned to treatment with buprenorphine (8 mg/day) or methadone (60 mg/day) for a period of 6 months. The two compounds did not show any significant difference with regard to urinalyses: the average percentage of analyses proving negative was 60.4% for patients assigned to buprenorphine, and 65.5% for those assigned to methadone. With regard to retention, a non-significant trend in favour of methadone was observed. Patients completing the trial improved significantly in terms of psychosocial adjustment and global functioning, as ascertained by the DSM-IV-GAF and symptom checklist-90 (SCL-90) scales, and this was independent of the treatment group. Finally, in the case of buprenorphine, patients who dropped out differed significantly from those who stayed, in terms of a higher level of psychopathological symptoms, and a lower level of psychosocial functioning. The results of the study further support the utility of buprenorphine for the treatment of opioid dependence.", "Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed, but its efficacy and safety have not been well studied.\n We conducted a multicenter, randomized, placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine (16 mg) in combination with naloxone (4 mg), buprenorphine alone (16 mg), or placebo given daily for four weeks. The primary outcome measures were the percentage of urine samples negative for opiates and the subjects' self-reported craving for opiates. Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone (at daily doses of up to 24 mg and 6 mg, respectively) and another 11 persons who received this combination only during the trial.\n The double-blind trial was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo. The proportion of urine samples that were negative for opiates was greater in the combined-treatment and buprenorphine groups (17.8 percent and 20.7 percent, respectively) than in the placebo group (5.8 percent, P<0.001 for both comparisons); the active-treatment groups also reported less opiate craving (P<0.001 for both comparisons with placebo). Rates of adverse events were similar in the active-treatment and placebo groups. During the open-label phase, the percentage of urine samples negative for opiates ranged from 35.2 percent to 67.4 percent. Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated.\n Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting.\n Copyright 2003 Massachusetts Medical Society", "The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence, but there are few long-term and placebo-controlled studies of its effectiveness. We aimed to assess the 1-year efficacy of buprenorphine in combination with intensive psychosocial therapy for treatment of heroin dependence.\n 40 individuals aged older than 20 years, who met DSM-IV criteria for opiate dependence for at least 1 year, but did not fulfil Swedish legal criteria for methadone maintenance treatment were randomly allocated either to daily buprenorphine (fixed dose 16 mg sublingually for 12 months; supervised daily administration for a least 6 months, possible take-home doses thereafter) or a tapered 6 day regimen of buprenorphine, thereafter followed by placebo. All patients participated in cognitive-behavioural group therapy to prevent relapse, received weekly individual counselling sessions, and submitted thrice weekly supervised urine samples for analysis to detect illicit drug use. Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat.\n 1-year retention in treatment was 75% and 0% in the buprenorphine and placebo groups, respectively (p=0.0001; risk ratio 58.7 [95% CI 7.4-467.4]). Urine screens were about 75% negative for illicit opiates, central stimulants, cannabinoids, and benzodiazepines in the patients remaining in treatment.\n The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious, and should be added to the treatment options available for individuals who are dependent on heroin.", "Physicians may prescribe buprenorphine for opioid agonist maintenance treatment outside of narcotic treatment programs, but treatment guidelines for patients with co-occurring cocaine and opioid dependence are not available. This study compares effects of buprenorphine and methadone and evaluates the efficacy of combining contingency management with maintenance treatment for patients with co-occurring cocaine and opioid dependence.\n Subjects with cocaine and opioid dependence (N=162) were provided manual-guided counseling and randomly assigned in a double-blind design to receive daily sublingual buprenorphine (12-16 mg) or methadone (65-85 mg p.o.) and to contingency management or performance feedback. Contingency management subjects received monetary vouchers for opioid- and cocaine-negative urine tests, which were conducted three times a week; voucher value escalated during the first 12 weeks for consecutive drug-free tests and was reduced to a nominal value in weeks 13-24. Performance feedback subjects received slips of paper indicating the urine test results. The primary outcome measures were the maximum number of consecutive weeks abstinent from illicit opioids and cocaine and the proportion of drug-free tests. Analytic models included two-by-two analysis of variance and mixed-model repeated-measures analysis of variance.\n Methadone-treated subjects remained in treatment significantly longer and achieved significantly longer periods of sustained abstinence and a greater proportion drug-free tests, compared with subjects who received buprenorphine. Subjects receiving contingency management achieved significantly longer periods of abstinence and a greater proportion drug-free tests during the period of escalating voucher value, compared with those who received performance feedback, but there were no significant differences between groups in these variables during the entire 24-week study.\n Methadone may be superior to buprenorphine for maintenance treatment of patients with co-occurring cocaine and opioid dependence. Combining methadone or buprenorphine with contingency management may improve treatment outcome.", "To evaluate the effectiveness of buprenorphine compared with methadone maintenance therapy in opiate addicts over a treatment period of 24 weeks.\n Subjects were randomized to receive either buprenorphine or methadone in an open, comparative study.\n Subjects were recruited and treated at the drug addiction outpatient clinic at the University of Vienna.\n Sixty subjects (19 females and 41 males) who met DSM-IV criteria for opioid dependence and were seeking treatment.\n Subjects received either sublingual buprenorphine (2-mg or 8-mg tablets; maximum daily dose 8 mg) or oral methadone (racemic D -/+ L-methadone; maximum daily dose 80 mg). A stable dose was maintained following the 6-day induction phase.\n Assessment of treatment retention and illicit substance use (opiates, cocaine and benzodiazepines) was made by urinalysis.\n The retention rate was significantly better in the methadone maintained group (p < 0.05) but subjects completing the study in the buprenorphine group had significantly lower rates of illicit opiate consumption (p = 0.04).\n The results support the superiority of methadone with respect to retention rate. However, they also confirm previous reports of buprenorphine use as an alternative in maintenance therapy for opiate addiction, suggesting that a specific subgroup may be benefiting from buprenorphine. This is the first comparative trial to use sublingual buprenorphine tablets: previously published comparison studies refer to 30% solutions of buprenorphine in alcohol.", "This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind, randomized, 6-week trial using a flexible dosing procedure. Fifty-eight patients seeking treatment for opioid dependence were recruited in three outpatient facilities and randomly assigned to substitution with buprenorphine or methadone. The retention rate was significantly better in the methadone maintained group (90 vs. 56%; P<0.001). Subjects completing the study in both the treatment groups had similar proportions of opioid positive urine samples (buprenorphine 62%; methadone 59%) and positive urine specimens, as well as mean heroin craving scores decreased significantly over time (P=0.035 and P<0.001). The proportion of cocaine-positive toxicology results did not differ between groups. At week six mean stabilization doses were 10.5 mg per day for the sublingual buprenorphine tablet, and 69.8 mg per day for methadone, respectively. Patient performance during maintenance was similar in both the groups. The high attrition rate in the buprenorphine group during the induction phase might reflect inadequate induction doses. Thus, buprenorphine is a viable alternative for methadone in short-term maintenance treatment for heroin dependence if treatment induction is done with adequate dosages.", "To evaluate the effect of a 4 mg/day sublingual dose of buprenorphine in the maintenance treatment of opium dependence in comparison with a 1 mg/day dose over an 18-week treatment period. As a secondary objective, the results were determined concurrently for subjects treated with a 2 mg/day dose.\n Subjects were assigned randomly to three dosage groups.\n 330 consecutive (320 men and 10 women) opium addicts who met the DSM-IV criteria for opioid dependence and were seeking treatment.\n Subjects received a 1, 2 or 4 mg/day dose of buprenorphine and were treated in an outpatient clinic where they also received a weekly 1-hour clinical counseling session.\n Addiction Severity Index, retention in treatment, and illegal opioid use as determined by random urine testing.\n The mean age was 37.5 years (SD=11.4, range 19-72). Overall, 194 (58.8%) of the patients completed the 18 week study. Completion rates by dosage groups were 47.3% for the 1 mg group, 58.2% for the 2 mg group and 70.9% for the 4 mg group (chi(2)=12.7, df=2, P=0.0017).\n The results support the efficacy and safety of buprenorphine for opium addiction and suggest that an adequate dose of buprenorphine would help to increase the success rate.", "Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)", "The goal of this study was to compare the effects of 1, 3 and 8 mg per day doses of buprenorphine in the maintenance treatment of opium-dependent subjects in Iran over a treatment period of 12 months. Participants were randomized to three equal groups (171 subjects per group) of opium-dependent individuals who met the DSM-IV criteria for opioid dependence and were seeking treatment. They were treated in an urban outpatient clinic, offering a 1-hour weekly individual counseling session. Overall, 282 subjects (55%) completed the 12 months study. Completion rates by dosage group were 46 (26.9%) for the 1 mg dose group, 102 (59.6%) for the 3 mg dose group, and 134 (78.4%) for the 8 mg dose group (p =.000). These findings are consistent with previous reports of effective buprenorphine use in western countries as a suitable maintenance treatment for opium dependence." ]

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[ "Efficacy and tolerability of atorvastatin/fenofibrate fixed-dose combination tablet compared with atorvastatin and fenofibrate monotherapies in patients with dyslipidemia: a 12-week, multicenter, double-blind, randomized, parallel-group study.", "Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.", "Effects of atorvastatin on dyslipidaemia in uraemic patients on peritoneal dialysis.", "Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin.", "Effects of statin on small dense low-density lipoprotein cholesterol and remnant-like particle cholesterol in heterozygous familial hypercholesterolemia.", "The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: a comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type IIa and type IIb hyperlipidemia.", "Effect of atorvastatin on postprandial lipoprotein metabolism in hypertriglyceridemic patients.", "Atorvastatin increases low-density lipoprotein size and enhances high-density lipoprotein cholesterol concentration in male, but not in female patients with familial hypercholesterolemia.", "[Effect of atorvastatin on endothelial function in patients with familial hypercholesterolemia].", "Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: the Vytorin Versus Atorvastatin (VYVA) study.", "Pleiotropic effects of atorvastatin in heart failure: role in oxidative stress, inflammation, endothelial function, and exercise capacity.", "Monocyte gene-expression profile in men with familial combined hyperlipidemia and its modification by atorvastatin treatment.", "A Multicenter, Placebo-Controlled, Dose-Ranging Study of Atorvastatin.", "Comparison of effects of simvastatin versus atorvastatin on oxidative stress in patients with coronary heart disease.", "[Atorvastatin in treatment of patients with coronary heart disease and dislipidemiya and high general risk: efficiency and safety estimation. Design and main results of ATLANTIKA].", "Effects of CoQ10 supplementation on plasma lipoprotein lipid, CoQ10 and liver and muscle enzyme levels in hypercholesterolemic patients treated with atorvastatin: a randomized double-blind study.", "A randomized, placebo-controlled trial to evaluate the efficacy, safety, and pharmacodynamic interaction of coadministered amlodipine and atorvastatin in 1660 patients with concomitant hypertension and dyslipidemia: the respond trial.", "Atorvastatin improves diabetic dyslipidemia and increases lipoprotein lipase activity in vivo.", "Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial.", "Comparison effect of atorvastatin (10 versus 80 mg) on biomarkers of inflammation and oxidative stress in subjects with metabolic syndrome.", "Effects of rosuvastatin on lipids, lipoproteins and apolipoproteins in the dyslipidaemia of diabetes.", "Effects of early administration of atorvastatin treatment on thrombotic process in normocholesterolemic patients with unstable angina.", "Effects of atorvastatin treatment on sICAM-1 and plasma nitric oxide levels in hypercholesterolemic subjects.", "Effects of switching statins on achievement of lipid goals: Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study.", "Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure.", "Arterial destiffening with atorvastatin in overweight and obese middle-aged and older adults.", "Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia.", "[Effect of atorvastatin therapy on the level of secretory phospholipase A2 group IIA and on the modification of low density lipoproteins in patients with ischemic heart disease].", "Effects of micronized fenofibrate versus atorvastatin in the treatment of dyslipidaemic patients with low plasma HDL-cholesterol levels: a 12-week randomized trial.", "The effect of low-dose atorvastatin on circulating monocyte chemoattractant protein-1 in patients with type 2 diabetes complicated by hyperlipidemia.", "Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus.", "Effect of atorvastatin on chylomicron remnant metabolism in visceral obesity: a study employing a new stable isotope breath test.", "LDL-C/HDL-C ratio in subjects with cardiovascular disease and a low HDL-C: results of the RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport) study.", "Comparison of the efficacy and tolerability of policosanol with atorvastatin in elderly patients with type II hypercholesterolaemia.", "Resistant arterial hypertension and hyperlipidemia: atorvastatin, not vitamin C, for blood pressure control.", "Comparative effects of 10-mg versus 80-mg Atorvastatin on high-sensitivity C-reactive protein in patients with stable coronary artery disease: results of the CAP (Comparative Atorvastatin Pleiotropic effects) study.", "Relationship between insulin resistance and effect of atorvastatin in non-diabetic subjects.", "Lipid-altering changes and pleiotropic effects of atorvastatin in patients with hypercholesterolemia.", "Atorvastatin effect on the distribution of high-density lipoprotein subfractions and human paraoxonase activity.", "hsCRP and HDL effects of statins trial (CHEST): rapid effect of statin therapy on C-reactive protein and high-density lipoprotein levels A clinical investigation.", "Plasma fibronectin level and its relationships with lipids, lipoproteins and C-reactive protein in patients with dyslipidaemia during lipid-lowering therapy.", "Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease.", "Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor.", "A 52-week, randomized, open-label, parallel-group comparison of the tolerability and effects of pitavastatin and atorvastatin on high-density lipoprotein cholesterol levels and glucose metabolism in Japanese patients with elevated levels of low-density lipoprotein cholesterol and glucose intolerance.", "An assessment of the efficacy of atorvastatin in achieving LDL cholesterol target levels in patients with coronary heart disease: a general practice study.", "Efficacy and safety of combination therapy with niacin extended-release and simvastatin versus atorvastatin in patients with dyslipidemia: The SUPREME Study.", "Treating to target patients with primary hyperlipidaemia: comparison of the effects of ATOrvastatin and ROSuvastatin (the ATOROS study).", "Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial).", "A randomized trial of the effects of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia. Collaborative Atorvastatin Study Group.", "High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol.", "Statin therapy for the prevention of atrial fibrillation trial (SToP AF trial).", "Correlation of non-high-density lipoprotein cholesterol with apolipoprotein B: effect of 5 hydroxymethylglutaryl coenzyme A reductase inhibitors on non-high-density lipoprotein cholesterol levels.", "Effect of monthly atorvastatin treatment on hemostasis.", "Effect of monthly atorvastatin and fenofibrate treatment on monocyte chemoattractant protein-1 release in patients with primary mixed dyslipidemia.", "[Assessment of hypolipidemic efficacy and safety of various doses of atorvastatin].", "Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary heart disease.", "The effect of atorvastatin on platelet function in patients with coronary artery disease.", "Short-term effects of atorvastatin on bone turnover in male patients with hypercholesterolemia.", "Lowering effects of four different statins on serum triglyceride level.", "Age-dependent effects of atorvastatin on biochemical bone turnover markers: a randomized controlled trial in postmenopausal women.", "Efficacy and safety of rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: a randomized, controlled trial.", "Different effect of statins on platelet oxidized-LDL receptor (CD36 and LOX-1) expression in hypercholesterolemic subjects.", "Effect of atorvastatin on different fibrinolyis mechanisms in hypercholesterolemic subjects.", "Different effect induced by treatment with several statins on monocyte tissue factor expression in hypercholesterolemic subjects.", "Impact of atorvastatin on serum vaspin levels in hypercholesterolemic patients with moderate cardiovascular risk.", "Effects of statin treatment on uric acid homeostasis in patients with primary hyperlipidemia.", "Effects of rosuvastatin and atorvastatin on LDL and HDL particle concentrations in patients with metabolic syndrome: a randomized, double-blind, controlled study.", "Atorvastatin reduces macrophage accumulation in atherosclerotic plaques: a comparison of a nonstatin-based regimen in patients undergoing carotid endarterectomy.", "Multicenter collaborative randomized parallel group comparative study of pitavastatin and atorvastatin in Japanese hypercholesterolemic patients: collaborative study on hypercholesterolemia drug intervention and their benefits for atherosclerosis prevention (CHIBA study).", "Effects of atorvastatin on serum lipids of patients with familial hypercholesterolaemia.", "Placebo-controlled trial of high-dose atorvastatin in patients with severe cerebral small vessel disease.", "Comparison of rosuvastatin versus atorvastatin in South-Asian patients at risk of coronary heart disease (from the IRIS Trial).", "Torcetrapib differentially modulates the biological activities of HDL2 and HDL3 particles in the reverse cholesterol transport pathway.", "A multi-center, open label, crossover designed prospective study evaluating the effects of lipid lowering treatment on steroid synthesis in patients with Type 2 diabetes (MODEST Study).", "Gender differences in short-term effects of atorvastatin on lipid profile, fibrinolytic parameters, and endothelial function.", "Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia.", "Atorvastatin and the dyslipidemia of early renal failure.", "Effects of atorvastatin on red-blood cell Na(+)/Li(+) countertransport in hyperlipidemic patients with and without hypertension.", "Differential effect of atorvastatin and fenofibrate on plasma oxidized low-density lipoprotein, inflammation markers, and cell adhesion molecules in patients with type 2 diabetes mellitus.", "Atorvastatin treatment beneficially alters the lipoprotein profile and increases low-density lipoprotein particle diameter in patients with combined dyslipidemia and impaired fasting glucose/type 2 diabetes.", "Differential effect of fenofibrate and atorvastatin on in vivo kinetics of apolipoproteins B-100 and B-48 in subjects with type 2 diabetes mellitus with marked hypertriglyceridemia.", "Comparison of efficacy and safety of atorvastatin (10mg) with simvastatin (10mg) at six weeks. ASSET Investigators.", "Comparative study of low doses of rosuvastatin and atorvastatin on lipid and glycemic control in patients with metabolic syndrome and hypercholesterolemia.", "A double-blind trial on the effects of atorvastatin on glycemic control in Japanese diabetic patients with hypercholesterolemia.", "A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: the treat-to-target (3T) study.", "Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia.", "Atorvastatin increases HDL cholesterol in hypercholesterolemic patients. Evidence of a relationship with baseline HDL cholesterol.", "Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE).", "3'UTR/T polymorphism of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is associated with modified anti-platelet activity of atorvastatin in hypercholesterolemic subjects.", "Treating to meet NCEP-recommended LDL cholesterol concentrations with atorvastatin, fluvastatin, lovastatin, or simvastatin in patients with risk factors for coronary heart disease.", "Time-dependent effect of statins on platelet function in hypercholesterolaemia.", "A comparative study with rosuvastatin in subjects with metabolic syndrome: results of the COMETS study.", "Atorvastatin enhances the plasma clearance of chylomicron-like emulsions in subjects with atherogenic dyslipidemia: relevance to the in vivo metabolism of triglyceride-rich lipoproteins.", "Effects of atorvastatin (10 mg) on hemostatic and inflammatory parameters in hyperlipidemic patients with angiographically proven coronary artery disease.", "Effects of atorvastatin and vitamin E on lipoproteins and oxidative stress in dialysis patients: a randomised-controlled trial.", "Short-term atorvastatin treatment improves endothelial function in hypercholesterolemic women.", "Comparison of efficacy and safety of rosuvastatin versus atorvastatin in African-American patients in a six-week trial.", "Comparison of the efficacy of atorvastatin versus cerivastatin in primary hypercholesterolemia.", "Atorvastatin but not L-arginine improves endothelial function in type I diabetes mellitus: a double-blind study.", "Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively.", "Influence of SCARB1 polymorphisms on serum lipids of hypercholesterolemic individuals treated with atorvastatin.", "CYP3A53A allele is associated with reduced lowering-lipid response to atorvastatin in individuals with hypercholesterolemia.", "Short-term effect of low-dose atorvastatin on haemorrheological parameters, platelet aggregation and endothelial function in patients with cerebrovascular disease and hyperlipidaemia.", "The effects of lipid-lowering therapy on paraoxonase activities and their relationships with the oxidant-antioxidant system in patients with dyslipidemia.", "Plasma Coenzyme Q10 Predicts Lipid-lowering Response to High-Dose Atorvastatin.", "Efficacy and safety of statins in hypercholesterolemia with emphasis on lipoproteins.", "Atorvastatin and quinapril inhibit blood coagulation in patients with coronary artery disease following 28 days of therapy.", "Achievement of target plasma cholesterol levels in hypercholesterolaemic patients being treated in general practice.", "Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients.", "Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status.", "Short term effect of atorvastatin and vitamin E on serum levels of C3, a sensitive marker of the risk of myocardial infarction in men.", "Efficacy and safety of a new hydroxymethylglutaryl-coenzyme A reductase inhibitor, atorvastatin, in patients with combined hyperlipidemia: comparison with fenofibrate.", "High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial.", "The human paraoxonase-1 phenotype modifies the effect of statins on paraoxonase activity and lipid parameters.", "Short-term effect of atorvastatin on ischaemic threshold in hypercholesterolaemic patients with stable ischaemic heart disease.", "Short- and long-term elevation of autoantibody titers against oxidized LDL in patients with acute coronary syndromes. Role of the lipoprotein-associated phospholipase A2 and the effect of atorvastatin treatment.", "Influence of atorvastatin on apolipoprotein E and AI kinetics in patients with type 2 diabetes.", "Comparative long-term efficacy and tolerability of pitavastatin 4 mg and atorvastatin 20-40 mg in patients with type 2 diabetes mellitus and combined (mixed) dyslipidaemia.", "A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial.", "Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study.", "The SLIM Study: Slo-Niacin® and Atorvastatin Treatment of Lipoproteins and Inflammatory Markers in Combined Hyperlipidemia.", "The comparison of the effects of standard 20 mg atorvastatin daily and 20 mg atorvastatin every other day on serum LDL-cholesterol and high sensitive C-reactive protein levels.", "[Noninvasive assessment of the effect of atorvastatin on coronary microvasculature and endothelial function in patients with dyslipidemia].", "Effects of different statin treatments on small dense low-density lipoprotein in patients with metabolic syndrome.", "Early effects of simvastatin versus atorvastatin on oxidative stress and proinflammatory cytokines in hyperlipidemic subjects.", "Flow-mediated dilation in patients with coronary artery disease is enhanced by high dose atorvastatin compared to combined low dose atorvastatin and ezetimibe: results of the CEZAR study.", "Effects of short-term atorvastatin treatment on global fibrinolytic capacity, and sL-selectin and sFas levels in hyperlipidemic patients with coronary artery disease.", "Effect of atorvastatin upon platelet activation in hypercholesterolemia, evaluated by flow cytometry.", "Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients.", "Efficacy and safety of ABT-335 (fenofibric acid) in combination with atorvastatin in patients with mixed dyslipidemia.", "Comparative effects of atorvastatin, simvastatin, and fenofibrate on serum homocysteine levels in patients with primary hyperlipidemia.", "Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia.", "The effect of atorvastatin therapy on lecithin:cholesterol acyltransferase, cholesteryl ester transfer protein and the antioxidant paraoxonase.", "Comparative effects of simvastatin and atorvastatin in hypercholesterolemic patients with characteristics of metabolic syndrome.", "Efficacy of atorvastatin in achieving National Cholesterol Education Program low-density lipoprotein targets in women with severe dyslipidemia and cardiovascular disease or risk factors for cardiovascular disease: The Women's Atorvastatin Trial on Cholesterol (WATCH).", "Effects of atorvastatin on ventricular late potentials and repolarization dispersion in patients with hypercholesterolemia.", "Effect of a new HMG-CoA reductase inhibitor, atorvastatin, on lipids, apolipoproteins and lipoprotein particles in patients with elevated serum cholesterol and triglyceride levels.", "Prolonged inhibition of cholesterol synthesis explains the efficacy of atorvastatin.", "Leukocyte and endothelial adhesion molecules in patients with hypercholesterolemia: the effect of atorvastatin treatment.", "Effects of atorvastatin 20 mg, rosuvastatin 10 mg, and atorvastatin/ezetimibe 5 mg/5 mg on lipoproteins and glucose metabolism.", "Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I.", "Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid.", "Atorvastatin has an important acute anti-inflammatory effect in patients with acute coronary syndrome: results of a randomized, double-blind, placebo-controlled study.", "Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study)", "Safety and efficacy of ezetimibe/simvastatin combination versus atorvastatin alone in adults ≥65 years of age with hypercholesterolemia and with or at moderately high/high risk for coronary heart disease (the VYTELD study).", "The effects of statin monotherapy and low-dose statin/ezetimibe on lipoprotein-associated phospholipase A₂.", "The effect of atorvastatin on erythrocyte membranes and serum lipids in patients with type-2 hypercholesterolemia.", "Lipid and apoprotein changes during atorvastatin up-titration in hemodialysis patients with hypercholesterolemia: a placebo-controlled study.", "Distinct effects of pitavastatin and atorvastatin on lipoprotein subclasses in patients with Type 2 diabetes mellitus.", "Comparison of rosuvastatin versus atorvastatin in Hispanic-Americans with hypercholesterolemia (from the STARSHIP trial).", "High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia.", "Comparison of rosuvastatin versus atorvastatin in patients with heterozygous familial hypercholesterolemia.", "Comparison of the efficacy and tolerability of pitavastatin and atorvastatin: an 8-week, multicenter, randomized, open-label, dose-titration study in Korean patients with hypercholesterolemia.", "Effect of atorvastatin on lipoprotein (a) and interleukin-10: a randomized placebo-controlled trial.", "Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia.", "MBX-8025, a novel peroxisome proliferator receptor-delta agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin.", "Neutrophil superoxide anion generation during atorvastatin and fluvastatin therapy used in coronary heart disease primary prevention.", "Efficacy and safety of ezetimibe co-administered with atorvastatin in untreated patients with primary hypercholesterolaemia and coronary heart disease.", "Contribution of apo CIII reduction to the greater effect of 12-week micronized fenofibrate than atorvastatin therapy on triglyceride levels and LDL size in dyslipidemic patients.", "Action of atorvastatin in combined hyperlipidemia : preferential reduction of cholesteryl ester transfer from HDL to VLDL1 particles.", "Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia.", "Atorvastatin reduces postprandial accumulation and cholesteryl ester transfer protein-mediated remodeling of triglyceride-rich lipoprotein subspecies in type IIb hyperlipidemia.", "Discovery Belux: comparison of rosuvastatin with atorvastatin in hypercholesterolaemia.", "Atorvastatin effects on SREBF1a and SCAP gene expression in mononuclear cells and its relation with lowering-lipids response.", "Effect of atorvastatin on the expression of CD40 ligand and P-selectin on platelets in patients with hypercholesterolemia.", "Inhibition of CETP by torcetrapib attenuates the atherogenicity of postprandial TG-rich lipoproteins in type IIB hyperlipidemia.", "Comparison of Ezetimibe/Simvastatin 10/20 mg Versus Atorvastatin 20 mg in Achieving a Target Low Density Lipoprotein-Cholesterol Goal for Patients With Very High Risk.", "Atorvastatin reduces sympathetic activity and increases baroreceptor reflex sensitivity in patients with hypercholesterolaemia and systemic arterial hypertension.", "Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia.", "Short-term effect of atorvastatin on endothelial function in healthy offspring of parents with type 2 diabetes mellitus.", "Plasma mevalonic acid, an index of cholesterol synthesis in vivo, and responsiveness to HMG-CoA reductase inhibitors in familial hypercholesterolaemia.", "Effect of atorvastatin on type 2 diabetic dyslipidemia.", "Ezetimibe/simvastatin vs atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia: the VYTAL study.", "Atorvastatin reduces plasma levels of factor VII activity and factor VII antigen in patients with hyperlipidemia.", "Treatment with atorvastatin alters the ratio of interleukin-12/interleukin-10 gene expression [corrected].", "Increased plasma levels of oxysterols, in vivo markers of oxidative stress, in patients with familial combined hyperlipidemia: reduction during atorvastatin and fenofibrate therapy.", "Comparison of atorvastatin versus fenofibrate in reaching lipid targets and influencing biomarkers of endothelial damage in patients with familial combined hyperlipidemia.", "Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia.", "Comparison of once-daily, niacin extended-release/lovastatin with standard doses of atorvastatin and simvastatin (the ADvicor Versus Other Cholesterol-Modulating Agents Trial Evaluation [ADVOCATE]).", "Statin therapy has no significant effect on skin tissue cholesterol: results from a prospective randomized trial.", "Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy.", "[The comparison of simvastatin and atorvastatin effects on hemostatic parameters in patients with hyperlipidemia type II].", "The effect of high dose atorvastatin therapy on lipids and lipoprotein subfractions in overweight patients with type 2 diabetes.", "Comparative lipid-lowering effects of policosanol and atorvastatin: a randomized, parallel, double-blind, placebo-controlled trial.", "Treatment of heterozygous familial hypercholesterolemia: atorvastatin vs simvastatin.", "Effects of atorvastatin on nuclear magnetic resonance-defined lipoprotein subclasses and inflammatory markers in patients with hypercholesterolemia.", "A randomized, double-blind, placebo-controlled, 8-week study to evaluate the efficacy and safety of once daily atorvastatin (10 mg) in patients with elevated LDL-cholesterol.", "Atorvastatin therapy decreases androstenedione and dehydroepiandrosterone sulphate concentrations in patients with polycystic ovary syndrome: randomized controlled study.", "Hemostatic effects of atorvastatin versus simvastatin.", "Impact of Vitamin E supplementation on lipoprotein peroxidation and composition in Type 1 diabetic patients treated with Atorvastatin.", "Efficacy and tolerability of a generic and a branded formulation of atorvastatin 20 mg/d in hypercholesterolemic Korean adults at high risk for cardiovascular disease: a multicenter, prospective, randomized, double-blind, double-dummy clinical trial.", "Effects of rosiglitazone alone and in combination with atorvastatin on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus.", "Effect of atorvastatin withdrawal on circulating coenzyme Q10 concentration in patients with hypercholesterolemia.", "Effects of atorvastatin and atorvastatin withdrawal on soluble CD40L and adipocytokines in patients with hypercholesterolaemia.", "The effects of atorvastatin on endothelial function in diabetic patients and subjects at risk for type 2 diabetes.", "Effect of correcting serum cholesterol levels on erectile function in patients with vasculogenic erectile dysfunction.", "The effect of atorvastatin on serum lipids, lipoprotein(a) and plasma fibrinogen levels in primary dyslipidaemia--a pilot study involving serial sampling.", "Atorvastatin downregulates monocyte CD36 expression, nuclear NFkappaB and TNFalpha levels in type 2 diabetes.", "Pharmacogenetic predictors of statin-mediated low-density lipoprotein cholesterol reduction and dose response.", "Efficacy and safety of coadministered amlodipine and atorvastatin in patients with hypertension and dyslipidemia: results of the AVALON trial.", "Effect of atorvastatin on LDL oxidation and antioxidants in normocholesterolemic type 2 diabetic patients.", "Comparative efficacy and safety of low-dose pitavastatin versus atorvastatin in patients with hypercholesterolemia.", "Effect of pretreatment vitamin D levels on in vivo effects of atorvastatin on bone metabolism in patients with heterozygous familial hypercholesterolemia.", "Efficacy and tolerability of rosuvastatin and atorvastatin when force-titrated in patients with primary hypercholesterolemia: results from the ECLIPSE study.", "Atorvastatin administration after percutaneous coronary intervention in patients with coronary artery disease and normal lipid profiles: impact on plasma adiponectin level.", "Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY (MERCURY) II.", "The effect of atorvastatin on postprandial lipaemia in overweight or obese women homozygous for apo E3.", "Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study.", "Cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with type 2 diabetes -- CORALL study.", "Effect of atorvastatin on low-density lipoprotein subtypes in patients with different forms of hyperlipoproteinemia and control subjects.", "Effect on high-density lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: results of the Comparative HDL Efficacy and Safety Study (CHESS).", "Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients.", "A randomized trial of the effect of statin and fibrate therapy on arterial function in CKD.", "Integrin expression on monocytes and lymphocytes in unstable angina short term effects of atorvastatin.", "Impact of atorvastatin treatment on platelet-activating factor acetylhydrolase and 15-F(2trans)-isoprostane in hypercholesterolaemic patients.", "Efficacy of atorvastatin compared with simvastatin in patients with hypercholesterolemia.", "Comparison of the effects of policosanol and atorvastatin on lipid profile and platelet aggregation in patients with dyslipidaemia and type 2 diabetes mellitus.", "Effect of statins on LDL particle size in patients with familial combined hyperlipidemia: a comparison between atorvastatin and pravastatin.", "Achieving low-density lipoprotein cholesterol goals in high-risk patients in managed care: comparison of rosuvastatin, atorvastatin, and simvastatin in the SOLAR trial." ]

[ "Coadministration of statin and fenofibrate monotherapies is frequently used to treat patients with dyslipidemia; however, a fixed-dose combination (FDC) tablet is not currently marketed.\n This study evaluates a new FDC tablet of atorvastatin 40 mg and fenofibrate 100 mg.\n This was a 12-week, multicenter, double-blind, randomized, parallel-group Phase IIb study. Adults with dyslipidemia (non-HDL-C >130 mg/dL and triglycerides [TG] > or =150 but < or =500 mg/dL) were randomly assigned in a 1:1:1 ratio to receive the FDC, atorvastatin 40 mg, or fenofibrate 145 mg for 12 weeks. Study medication was taken once daily in the evening, without regard to meals. Patients attended follow-up visits after 4, 8, and 12 weeks of the double-blind treatment. The primary efficacy end points were the mean percentage changes from baseline to the final visit (week 12) in non-HDL-C, HDL-C, and TG. Secondary variables were LDL-C, VLDL-C particle concentration, total cholesterol, apolipoprotein B, lipoprotein (a), high-sensitivity C-reactive protein, fibrinogen, homocysteine, creatinine, myeloperoxidase, and lipoprotein-associated phospholipase A2. Tolerability was assessed by adverse events, laboratory parameters, vital signs, physical examinations, and ECGs.\n Patients (n = 220) were aged 26 to 87 years; 115 (52.3%) were men and 105 (47.7%) were women; 189 (85.9%) were white, 17 (7.7%) were black, and 15 (6.8%) were Hispanic or Latino; and mean (SD) weight was 200.5 (40.85) lb (range, 103.5-367.4 lb). Previous treatments were statins (25.9% [57/220]), fibrates (1.8% [4/220]), and dietary supplements (25.5% [56/220]); 57.7% (127/220) of patients were treatment naive. Use of the FDC was associated with an improvement in non-HDL-C (-44.8%) that was significantly greater than with fenofibrate monotherapy (-16.1%; P < 0.001) but was not significantly different from that with atorvastatin monotherapy (-40.2%; P = NS). HDL-C increased significantly more in the FDC group (19.7%) than with atorvastatin (6.5%; P < 0.001) but was not significantly different from fenofibrate (18.2%; P = NS). TG lowering in the FDC group (-49.1%) was significantly greater than with both atorvastatin (-28.9%; P < 0.001) and fenofibrate (-27.8%; P = 0.001). LDL-C lowering in the FDC group (-42.3%) was significantly greater than with fenofibrate (-13.9%; P < 0.001) but not significantly different from atorvastatin (-43.1%; P = NS). The FDC had either comparable or significantly greater improvements in other lipid variables and multiple secondary variables. The FDC was generally well tolerated; the tolerability profile was consistent with those of atorvastatin and fenofibrate monotherapies. Treatment-emergent adverse events (ie, those occurring after the first dose of study medication) were recorded in 43 of 73 patients (58.9%) for the FDC, 49 of 74 (66.2%) for atorvastatin, and 48 of 73 (65.8%) for fenofibrate.\n In this 12-week study, patients with dyslipidemia treated with the 40/100-mg atorvastatin/ fenofibrate FDC had a significantly greater reduction in TG than those treated with atorvastatin 40 mg or higher-dose fenofibrate 145 mg. Treatment with the FDC was also associated with a significantly greater reduction in non-HDL-C compared with fenofibrate alone and a greater increase in HDL-C compared with atorvastatin alone. All treatments were generally well tolerated.\n Copyright 2009 Excerpta Medica Inc. All rights reserved.", "This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.47 mmol/L (250 mg/dl) and triglycerides < or =4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n = 132), rosuvastatin 5 mg (n = 128), rosuvastatin 10 mg (n = 129), or atorvastatin 10 mg (n = 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (-40% and -43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated.", "Our purpose was to evaluate the efficacy and safety of atorvastatin, a potent cholesterol- and triglyceride-lowering agent, in peritoneal dialysis patients with dyslipidaemia.\n Peritoneal dialysis patients with hypercholesterolaemia were treated for 4 months with atorvastatin at a starting dose of 10 mg. The dose could be increased to 20 or 40 mg in order to achieve the following targets: plasma LDL-cholesterol of 130 mg/dl for primary prevention of coronary heart disease, plasma LDL cholesterol of 100 mg/dl for secondary prevention, and plasma triglycerides of 200 mg/dl. Plasma lipid profile and liver and muscle enzyme levels were assessed at baseline and then monthly during treatment.\n Thirty-one patients with hypercholesterolaemia were included (16 males and 15 females; mean age 57+/-16 years; mean duration of peritoneal dialysis 27+/-17 months). Nineteen of the patients also had hypertriglyceridaemia and seven had diabetes. Twenty patients had no coronary history (primary prevention), whereas nine had experienced a coronary event (secondary prevention). In the primary and the secondary prevention patients, mean LDL-cholesterol levels (mg/dl) decreased significantly by 42 and 46% from 204+/-23 to 119+/-27 (P<0. 001) and 198+/-37 to 104+/-21 (P<0.001), and mean triglyceride levels (mg/dl) decreased by 37 and 26% from 289+/-132 to 186+/-92 (P<0.001) and 201+/-62 to 150+/-54 (P<0.001 respectively). Nineteen primary prevention and seven secondary prevention patients achieved the LDL-cholesterol target. The triglyceride target was achieved by 15 of the 19 hypertriglyceridaemic patients. Two patients stopped treatment (one because of gastrointestinal disturbances, the other because of an allergic skin reaction). After 4 months, there were no changes in enzyme levels.\n Atorvastatin is an effective and safe lipid-lowering agent for peritoneal dialysis patients with mixed dyslipidaemia.", "This study compared the efficacy and safety of atorvastatin, fluvastatin, lovastatin, and simvastatin in patients with documented atherosclerosis treated to U.S. National Cholesterol Education Program (NCEP) recommended low-density-lipoprotein (LDL) cholesterol concentration (< or = 100 mg/dl [2.59 mmol/liter]).\n For patients with advanced atherosclerosis, NCEP recommends lipid-lowering drug therapy if LDL cholesterol remains > or = 130 mg/dl (3.36 mmol/liter).\n A total of 318 men or women with documented atherosclerosis and LDL cholesterol > or = 130 mg/dl (3.36 mmol/liter) and < or = 250 mg/dl (6.5 mmol/liter), and triglycerides < or = 400 mg/dl (4.5 mmol/liter) participated in this 54-week, multicenter, open-label, randomized, parallel-group, active-controlled, treat-to-target study. Patients were titrated at 12-week intervals until the LDL cholesterol goal was reached. Number of patients reaching target LDL cholesterol levels and dose to reach target were evaluated.\n At the starting doses, atorvastatin 10 mg produced significantly greater decreases (p < 0.05) in plasma LDL cholesterol than the other treatments. Subsequently, the percentage of patients reaching goal at the starting dose was 32% for atorvastatin, 1% for fluvastatin, 10% for lovastatin and 22% for simvastatin. Atorvastatin-treated patients required a lower median dose than other treatments. Median doses at week 54 with the last available visit carried forward were atorvastatin 20 mg/day, fluvastatin 40 mg/day + colestipol 20 g/day, lovastatin 80 mg/day, simvastatin 40 mg/day.\n A significantly greater number (p < 0.05) of patients with confirmed atherosclerosis treated with atorvastatin reached the target LDL cholesterol concentration at the starting dose than patients treated with fluvastatin or lovastatin, and significantly fewer (p < 0.05) patients treated with atorvastatin required combination therapy with colestipol to achieve target LDL cholesterol concentrations than all other statins tested.", "The effects of statin on small dense low-density lipoprotein cholesterol (sd-LDL-C) and remnant-like particle cholesterol (RLP-C) levels in heterozygous familial hypercholesterolemia (FH) have not been examined. This study aimed to clarify the effects of statin on sd-LDL-C and RLP-C levels in heterozygous FH.\n Seventeen patients with heterozygous FH were randomly assigned to 2 mg/day pitavastatin or 10 mg/day atorvastatin. At baseline and 12 weeks after treatment with statin, we measured sd-LDL-C and RLP-C levels.\n Sd-LDL-C levels significantly decreased from 43 +/- 24 to 16 +/- 10 mg/dL (-63%, p=0.001) in the pitavastatin group, and from 44 +/- 17 to 19 +/- 10 mg/dL (-55%, p<0.001) in the atorvastatin group. RLP-C levels decreased from 8.4 +/- 2.8 to 6.6 +/- 2.7 mg/dL (-16%, p=0.156) in the pitava-statin group, and from 9.8 +/- 4.7 to 5.9 +/- 5.4 mg/dL (-45%, p=0.044) in the atorvastatin group. There were no significant differences in percent changes of sd-LDL-C (p=0.370) and RLP-C levels (p=0.097) between the two groups.\n Sd-LDL-C measured by the heparin-magnesium precipitation method and RLP-C levels in heterozygous FH were decreased by 12 weeks of statin therapy. Statin might have additional anti-atherogenic effects by reducing not only LDL-C but also sd-LDL-C and RLP-C.", "Hyperlipidemia is an important risk factor for atherosclerosis. Hemorheological factors contribute to morbidity and mortality in patients with dyslipidemia. We evaluated the effects of 3 antihyperlipidemic drugs (pravastatin, atorvastatin, and fenofibrate), which have different mechanisms of action and different patterns of action on lipid profiles, on erythrocyte deformability and fibrinogen levels in patients with type IIa and type IIb hyperlipidemia. Twenty-one patients ( 4 men and 17 women) with type IIa and IIb hyperlipidemia were randomized to 3 drugs (pravastatin 20 mg/d, atorvastatin 10 mg/d, fenofibrate 250 mg/d) for 8 weeks. Plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) analysis were performed on a BM-Hitachi 747-200 autoanalyzer (Hitachi-Roche, Tokyo, Japan). Fibrinogen analysis was performed according to Clauss method. Erythrocyte deformability was assessed with cell transit analysis device. There was no significant difference in body mass index, lipid profile, fibrinogen level, and erythrocyte deformability index values among the groups before treatment ( P > .05). In all groups, there were statistically significant reductions in total LDL-C levels ( P < .05). The triglyceride levels were significantly reduced in the atorvastatin and fenofibrate groups ( P < .05), but not in the pravastatin group ( P > .05). There was no significant change in HDL-C levels during the treatment with statins ( P > .05), but there was a significant increase in the fenofibrate group ( P < .05). Mean erythrocyte deformability index was improved in all the groups ( P < .05). There was no significant change in fibrinogen levels during the treatment of pravastatin and atorvastatin ( P > .05), but in fenofibrate group, fibrinogen levels were significantly decreased ( P < .05). The 3 groups of antihyperlipidemic drugs have beneficial effects on the erythrocyte deformability index. Only fenofibrate has significant beneficial effects on the fibrinogen levels.", "Postprandial lipoprotein metabolism is impaired in hypertriglyceridemia. It is unknown how and to what extent atorvastatin affects postprandial lipoprotein metabolism in hypertriglyceridemic patients. We evaluated the effect of 4 weeks of atorvastatin therapy (10 mg/day) on postprandial lipoprotein metabolism in 10 hypertriglyceridemic patients (age, 40 +/- 3 years; body mass index, 27 +/- 1 kg/m2; cholesterol, 5.74 +/- 0.34 mmol/l; triglycerides, 3.90 +/- 0.66 mmol/l; HDL-cholesterol, 0.85 +/- 0.05 mmol/l; and LDL-cholesterol, 3.18 +/- 0.23 mmol/l). Patients were randomized to be studied with or without atorvastatin therapy. Postprandial lipoprotein metabolism was evaluated with a standardized oral fat load. Plasma was obtained every 2 h for 14 h. Large triglyceride-rich lipoproteins (TRLs) (containing chylomicrons) and small TRLs (containing chylomicron remnants) were isolated by ultracentrifugation, and cholesterol, triglyceride, apolipoprotein B-100 (apoB-100), apoB-48, apoC-III, and retinyl-palmitate concentrations were determined. Atorvastatin significantly (P < 0.01) decreased fasting cholesterol (-27%), triglycerides (-43%), LDL-cholesterol (-28%), and apoB-100 (-31%), and increased HDL-cholesterol (+19%). Incremental area under the curve (AUC) significantly (P < 0.05) decreased for large TRL-cholesterol, -triglycerides, and -retinyl-palmitate, while none of the small TRL parameters changed. These findings contrast with the results in normolipidemic subjects, in which atorvastatin decreased the AUC for chylomicron remnants (small TRLs) but not for chylomicrons (large TRLs). We conclude that atorvastatin improves postprandial lipoprotein metabolism in addition to decreasing fasting lipid levels in hypertriglyceridemia. Such changes would be expected to improve the atherogenic profile.", "The effects of atorvastatin (Lipitor) were evaluated in 40 patients with familial hypercholesterolemia (FH). Following a 6 week drug-free baseline period 20 male and 20 female patients were treated with atorvastatin 40 mg once daily (QD) for the initial 6 weeks increasing to 80 mg QD during the following 6 weeks. Atorvastatin 40 and 80 mg resulted in a dose related reduction in LDL cholesterol of 44 and 50% (P<0.001), respectively. The reduction of triglycerides (TG) was 35% (P<0.001) with 40 and 80 mg atorvastatin. The lipoprotein lipase and the hepatic lipase activity decreased dose independently by 13% (P<0.05) and 18% (P<0.01), respectively. In males, a dose independent increase in high-density lipoprotein (HDL) cholesterol concentration was observed of 8%, (P<0.05). In females, the HDL cholesterol concentration did not change. Baseline LDL size in the females was significantly larger than in the males, being 268+/-6 A and 264+/-8 A (P<0.05), respectively. In males LDL size increased significantly from 264+/-8 A at baseline to269+/-6 A at 40 mg (P<0.05) and to 270+/-5 A (P<0.05) at 80 mg atorvastatin. In females LDL size did not change upon treatment with atorvastatin 40 and 80 mg QD. In conclusion, atorvastatin has the ability to decrease cholesterol and triglyceride concentrations as well as the activity of both lipoprotein and hepatic lipase activity. Additionally it has a favorable effect on LDL size and HDL cholesterol concentration in male, but not in female FH patients.", "To study the influence of treatment with HMG-CoA reductase inhibitor atorvastatin on endothelial function in patients with familial hypercholesterolemia type IIa.\n Sixteen patients (5m/11w, 51-/+3 years) with familial hypercholesterolemia were studied before and after 3 months of therapy with atorvastatin 20 mg/day. EDRF release test (D.Celermajer, 1992) was used to assess flow-mediated endothelium-dependent vasodilatation (FMD) of the brachial artery in response to reactive hyperemia. Plasma nitrite/nitrate (NOx) levels were measured as an indirect index of nitric oxide (NO) production in vivo using HPLC.\n Atorvastatin treatment resulted in a 32% reduction in total serum cholesterol (CH), 41% reduction in low density lipoprotein (LDL) CH, 16% reduction in triglycerides and a 21% increase in high density lipoprotein CH. Flow mediated dilatation (FMD) was impaired at baseline (5.8-/+0.9%) and significantly improved up to 9.5-/+0.9% after 3 month atorvastatin therapy (p<0.002). Change in FMD inversely correlated with baseline FMD (r = -0.58, p<0.05). There was no significant correlation between FMD and neither total serum CH nor LDL CH levels at baseline. During atorvastatin therapy significant reduction of plasma NOx levels occurred from 53.4-/+5.1 mcmol/l at baseline (range 42.6-86.2 mcmol/l) to 35.5-/+5.1 mcmol/l (18.4-46.0 mcmol/l) after treatment (p<0.02, n=7).\n In patients with familial hypercholesterolemia atorvastatin produced beneficial effect on endothelial function (increase in flow-mediated dilatation, decrease in NOx).", "Low-density lipoprotein cholesterol (LDL-C) is the primary therapeutic target in the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines. This study tested the hypothesis that ezetimibe/simvastatin, a lipid-lowering agent that inhibits both intestinal cholesterol absorption and cholesterol synthesis, provides greater LDL-C reductions than atorvastatin across dose ranges.\n This multicenter, double-blind, 6-week parallel-group study randomized 1902 patients with LDL-C above ATP III goal to atorvastatin (10, 20, 40, or 80 mg) or to ezetimibe/simvastatin (10/10, 10/20, 10/40, or 10/80 mg). Patients were stratified by prerandomization LDL-C level.\n At each milligram-equivalent statin dose comparison, and averaged across doses, ezetimibe/simvastatin provided greater LDL-C reductions (47%-59%) than atorvastatin (36%-53%). Ezetimibe/simvastatin 10/40 and 10/80 mg also provided significantly greater high-density lipoprotein cholesterol (HDL-C) increases than atorvastatin 40 and 80 mg. Triglyceride reductions were similar for all comparisons. More ezetimibe/simvastatin than atorvastatin patients with coronary heart disease (CHD) or CHD risk equivalents attained the ATP III LDL-C goal of <100 mg/dL and the optional LDL-C target of <70 mg/dL. C-reactive protein reductions were similar between treatment groups. Consecutive elevations in alanine aminotransferase and/or aspartate aminotransferase occurred in significantly more atorvastatin patients than ezetimibe/simvastatin patients. No myopathy or liver-related adverse events led to study discontinuation with either drug.\n Ezetimibe/simvastatin was more effective than atorvastatin in lowering LDL-C at each dose comparison and provided greater increases in HDL-C at the 40- and 80-mg statin dose. Ezetimibe/simvastatin is a highly efficacious, well-tolerated treatment option for hypercholesterolemic patients.", "Increased oxidative stress, a common feature in chronic heart failure, has been associated with inflammation, endothelial dysfunction, and extracellular matrix degradation. Statins have known anti-inflammatory and anti-oxidant effects; however, their role in chronic heart failure is still controversial.\n This was a prospective study of 38 patients with stable systolic chronic heart failure. Patients received a 4-week placebo course, followed by atorvastatin 20 mg/day for 8 weeks. Oxidative stress, inflammation and remodeling markers, brachial artery flow-mediated vasodilation, and 6-minute walk test were evaluated at baseline, 4, and 8 weeks.\n Mean age was 58 +/- 12. Mean left ventricular ejection fraction was 27% +/- 12%. No significant differences were observed between measurements at baseline and after placebo. Atorvastatin induced a significant decrease of matrix metalloproteinase-9 activity, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-6, and malondialdehyde, and a significant increase of endothelial superoxide dismutase activity when compared with placebo. No differences in tissue inhibitor of matrix metalloproteinase and matrix metalloproteinase-2 activities were observed. Atorvastatin use was associated with an improved flow-dependent brachial vasodilation and exercise capacity in the 6-minute walk test.\n In chronic heart failure patients, atorvastatin therapy is associated with a decrease of inflammation and extracellular matrix remodeling, improving both endothelial function and exercise capacity.", "The genetic origin of familial combined hyperlipidemia (FCH) is not well understood. We used microarray profiling of peripheral blood monocytes to search novel genes and pathways involved in FCH.\n Fasting plasma for determination of lipid profiles, inflammatory molecules and adipokines was obtained and peripheral blood monocytes were isolated from male FCH patients basally and after 4 weeks of atorvastatin treatment. Sex-, age- and adiposity-matched controls were also studied. Gene-expression profiles were analyzed using Affymetrix Human Genome U133A 2.0 GeneChip arrays.\n Analysis of gene expression by cDNA microarrays showed that 82 genes were differentially expressed in FCH monocytes compared with controls. Atorvastatin treatment modified the expression of 86 genes. Pathway analysis revealed the over-representation of the complement and coagulation cascades, the hematopoietic cell lineage and the arachidonic acid metabolism pathways. Changes in the expression of some genes, confirmed by real-time RT-PCR, (CD36, leucine-rich repeats and immunoglobulin-like domains-1, tissue factor pathway inhibitor 2, myeloid cell nuclear differentiation antigen, tumor necrosis factor receptor superfamily, member 25, CD96 and lipoprotein lipase), may be related to a proinflammatory environment in FCH monocytes, which is partially reversed by atorvastatin. Higher plasma levels of triglycerides and free fatty acids and lower levels of adiponectin in FCH patients could also trigger changes in gene expression that atorvastatin cannot modify.\n Our results show clear differences in gene expression in FCH monocytes compared with those of matched healthy controls, some of which are influenced by atorvastatin treatment.", "BACKGROUND: Coronary heart disease (CHD) is the number one cause of death in Western societies. Elevated levels of plasma low-density lipoprotein (LDL) cholesterol and triglycerides (TG) increase the risk for CHD. 3-Hydroxy-3-methylglutaryl conenzyme A (HMG-CoA) reductase inhibitors effectively reduce plasma cholesterol levels in patients with hypercholesterolemia. This study assesses the safety and dose-related effects of atorvastatin calcium on lipoprotein fractions in patients with LDL cholesterol levels between 160 mg/dL (4.1 mM) and 250 mg/dL (6.5 mM) or less and TG levels of 400 mg/dL (4.5 mM) or less. METHODS AND RESULTS: Sixty-five patients were enrolled in a 6-week, randomized, placebo-controlled, parallel-group study. Patients received placebo or atorvastatin 10, 20, 40, 60, or 80 mg once daily. Adjusted mean decreases in LDL cholesterol for patients receiving atorvastatin 10, 20, 40, 60, and 80 mg were 37%, 42%, 50%, 52%, and 59%, respectively, compared with a mean increase of 0.3% for patients receiving placebo; the differences between each of the atorvastatin dose groups and placebo were statistically significant (P =.0001). Total cholesterol, triglycerides, and apolipoprotein B were significantly reduced in atorvastatin groups (P =.0001). Adverse events were similar in the placebo and atorvastatin treatment groups. No patient had a serious adverse event or withdrew because of an adverse event during this study. CONCLUSIONS: Atorvastatin effectively lowered plasma LDL cholesterol, triglycerides, and apoB levels in a dose-related manner. Atorvastatin was well tolerated in hyperlipidemic patients over a 6-week period.", "HMG-CoA reductase inhibitors (statins) have antiatherogenic effects beyond their cholesterol-lowing effect. Whether atorvastatin has a stronger antioxidant effect than other statins is uncertain.\n To determine the effects of simvastatin and atorvastatin on markers of oxidative stress in patients with coronary heart disease (CHD).\n This study was comprised of 164 patients with CHD and a control population of 122 healthy subjects. The patients with CHD were divided into 2 groups and treated with either simvastatin 20 mg/day or atorvastatin 10 mg/day. The markers of oxidative stress were measured before and after 12 weeks of treatment.\n The effects of atorvastatin on reducing oxidative stress were significantly greater compared with those of simvastatin (P < 0.05). The changes in the markers of oxidative stress did not correlate with the changes in the plasma lipid profile (P > 0.05).\n This study suggests that atorvastatin reduces oxidative stress more effectively than simvastatin.\n Copyright 2010 Wiley Periodicals, Inc.", "nan", "The long-term efficacy and safety of HMG-CoA reductase inhibitors (statins) have been established in large multicenter trials. Inhibition of this enzyme, however, results in decreased synthesis of cholesterol and other products downstream of mevalonate, such as CoQ10 or dolichol. This was a randomized double-blind, placebo-controlled study that examined the effects of CoQ10 and placebo in hypercholesterolemic patients treated by atorvastatin. Eligible patients were given 10mg/day of atorvastatin for 16 weeks. Half of the patients (n=24) were supplemented with 100mg/day of CoQ10, while the other half (n=25) were given the placebo. Serum LDL-C levels in the CoQ10 group decreased by 43%, while in the placebo group by 49%. The HDL-C increment was more striking in the CoQ10 group than in the placebo group. All patients showed definite reductions of plasma CoQ10 levels in the placebo group, by 42%. All patients supplemented with CoQ10 showed striking increases in plasma CoQ10 by 127%. In conclusion atorvastatin definitely decreased plasma CoQ10 levels and supplementation with CoQ10 increased their levels. These changes in plasma CoQ10 levels showed no relation to the changes in serum AST, ALT and CK levels. Further studies are needed, however, for the evaluation of CoQ10 supplementation in statin therapy.", "Guidelines stress the importance of the simultaneous management of multiple cardiovascular risk factors. This can in part be achieved by coadministration of lipid-lowering and antihypertensive treatments. Potential pharmacodynamic interaction between drugs should be investigated as part of developing single-pill combinations. The Respond trial assessed whether combining amlodipine to treat hypertension and atorvastatin to treat dyslipidemia affected the action of either monotherapy. A total of 1660 hypertensive patients with dyslipidemia received 1 of 15 combinations of amlodipine (placebo, 5, or 10 mg) and atorvastatin (placebo, 10, 20, 40, or 80 mg) in a 3 x 5 factorial randomized, placebo-controlled design. At 8 weeks, combination-treated patients experienced dose-related and statistically significant reductions in systolic blood pressure, low-density lipoprotein cholesterol, and Framingham risk score. Overall, coadministered atorvastatin and amlodipine was well tolerated and without adverse pharmacodynamic interaction; combination treatment did not affect the low-density lipoprotein cholesterol-lowering efficacy and safety of atorvastatin, or the systolic blood pressure-lowering efficacy and safety of amlodipine.", "A major factor contributing to cardiovascular mortality in type 2 diabetes is dyslipidemia, characterized by low HDL cholesterol and high triglycerides, rather than elevated LDL cholesterol. Lipoprotein lipase (LPL) is the rate-limiting enzyme of triglyceride removal from plasma and has been implicated in atherosclerosis. Since treatment with statins significantly reduces cardiovascular morbidity in diabetes, we analyzed the lipid profile and LPL activities in 61 patients with type 2 diabetes before and 8 weeks after initiation of atorvastatin (40 mg) or placebo treatment. Lipid parameters and LPL activity were unchanged under treatment with placebo. Atorvastatin treatment resulted in a 30% reduction of total and a 45% reduction of LDL cholesterol (6.06 +/- 1.39 mmol/L versus 4.14 +/- 1.27 mmol/L and 4.11 +/- 1.13 mmol/L versus 2.27 +/- 0.89 mmol/L, both P < 0.0001). Triglycerides and VLDL cholesterol were also significantly reduced by statin therapy (2.24 +/- 2.11 mmol/L versus 1.82 +/- 1.46 mmol/L and 1.08 +/- 1.56 mmol/L versus 0.67 +/- 0.66 mmol/L, both P < 0.05). HDL cholesterol was not different between the atorvastatin and the placebo group. Compared to baseline, LPL activity was increased by 25% after atorvastatin treatment (213.0 +/- 28.1 nmol/mL/min versus 171.9 +/- 17.7 nmol/mL/min, P < 0.01). Our data demonstrate that atorvastatin induces a significant improvement of diabetic dyslipidemia and a significant increase of LPL activity. Since low LPL activity indicates an increased cardiovascular risk, the statin-mediated increase in LPL activity may help to explain the reduction of CAD in diabetic patients treated with statins.\n Copyright 2004 Elsevier Ireland Ltd", "Patients with systemic lupus erythematosus (SLE) have recognized reduction in endothelium-dependent vasodilation. Evidence demonstrates that statins are able to improve endothelial function independently on their hypolipemic action.\n To evaluate the efficacy of atorvastatin in improving vasodilation in SLE patients with and without conventional risk factors for coronary heart disease (CHD).\n Sixty-four SLE women, mean age 31 +/- 8 yrs, received atorvastatin 20 mg/day during 8 weeks. Thirty-one patients in this intervention group did not have conventional risk factors for CHD, while 33 others had hypertension, dyslipidaemia and/or obesity. Twenty-four SLE control patients, mean age 34 +/- 7.5 yrs, not receiving atorvastatin were followed during the same time period. High-resolution ultrasound was used to measure brachial artery diameter in resting conditions, during reactive hyperaemia and after sub-lingual glyceryl trinitrate (GTN). Measurements were performed at baseline and at the end of the study (8 weeks).\n Atorvastatin was associated with a significant increase in flow-mediated dilation (FMD) [3.8 (2.8-7.9%) vs 6.9 (4.2-10.7%), P < 0.001] while GTN-mediated dilation (GTND) was unaffected [20.9 (16.6-26.1%) vs 20.1(16.6-25.4%), P = 0.514]. FMD increase was observed in patients with conventional risk factors [4.1 (3.1-8.7%) vs 6.5 (4-10%), P = 0.046] and also for those without conventional risk factors for CHD [3.6 (2.6-7.3%) vs 7.1 (4.5-10.9%), P = 0.001]. Resting brachial artery diameter also increased significantly in patients receiving atorvastatin (2.79 +/- 0.30 mm vs 2.92 +/- 0.40 mm, P < 0.001). No significant difference in artery diameter and FMD was seen in control patients at the end of the study. When compared to the control patients, atorvastatin treatment was associated with significant increase in resting diameter (+0.13 +/- 0.1 mm vs -0.02 +/- 0.07 mm, P < 0.001) and FMD (+1.9 +/- 3.9% vs -0.3 +/- 1.8%, P = 0.009).\n Our results demonstrate that an 8-week 20 mg/day atorvastatin series improved endothelium-dependent vasodilation in SLE patients independently on the presence of conventional risk factors for atherosclerotic disease.", "Metabolic syndrome (MS), characterized by low-grade inflammation, confers an increased risk for cardiovascular disease. Statins, in addition to having lipid-lowering effects, have pleiotropic effects and decrease biomarkers of inflammation and oxidative stress. The Treating to New Target Study showed a greater decrease in low-density lipoprotein (LDL) cholesterol and cardiovascular events with atorvastatin 80 mg versus 10 mg in patients with MS with coronary heart disease. However, part of this benefit could be caused by the greater pleiotropic effects of the higher dose of atorvastatin. The dose-response effect of atorvastatin on biomarkers of inflammation and oxidative stress has not been investigated in subjects with MS. Thus, the dose-response effect of atorvastatin on biomarkers of inflammation (high-sensitivity C-reactive protein [hs-CRP], matrix metalloproteinase-9, and nuclear factor-kappaB [NF-kB] activity) and oxidative stress (oxidized LDL, urinary nitrotyrosine, F2-isoprostanes, and monocyte superoxide release) was tested in a randomized double-blind clinical trial in subjects with MS. Seventy subjects were randomly assigned to receive placebo or atorvastatin 10 or 80 mg/day for 12 weeks. A strong dose-response (atorvastatin 10 compared with 80 mg, p <0.05) was observed for changes in total, LDL (32% and 44% reduction), non-high-density lipoprotein (28% and 40% reduction), and oxidized LDL cholesterol (24% and 39% reduction) at atorvastatin 10 and 80 mg, respectively. Hs-CRP, matrix metalloproteinase-9, and NF-kB significantly decreased in the 80-mg atorvastatin group compared with baseline. In conclusion, this randomized trial of subjects with MS showed the superiority of atorvastatin 80 mg compared with its 10-mg dose in decreasing oxidized LDL, hs-CRP, matrix metalloproteinase-9, and NF-kB activity.", "To compare the effects of rosuvastatin and atorvastatin 10 and 20 mg on plasma lipid and lipoprotein profiles in patients with Type 2 diabetes mellitus and triglycerides < or = 6.0 mmol/l.\n A double-blind, randomized, multicentre study to assess the effect of rosuvastatin and atorvastatin, at 10 mg/day for 8 weeks followed by 20 mg/day for a further 8 weeks, on low-density lipoprotein cholesterol (LDL-C), together with a range of secondary lipid and lipoprotein end points.\n Rosuvastatin reduced mean LDL-C levels from baseline over 16 weeks by 57.4%, while atorvastatin reduced mean LDL-C levels by 46.0% over the same period. The difference in LDL-C reduction between treatments was statistically significant (P < 0.001). Rosuvastatin also produced statistically significantly greater mean reductions from baseline in levels of total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B and lipid ratios. More patients achieved European LDL-C (< 2.5 mmol/l) and total cholesterol (< 4.5 mmol/l) goals with rosuvastatin than with atorvastatin. Rosuvastatin was associated with a significantly (P < 0.049) greater mean percentage increase in glycated haemoglobin (HbA(1c)) from baseline compared with atorvastatin; however, patients in both treatment groups maintained good glycaemic control. Both rosuvastatin and atorvastatin were well tolerated.\n Greater reductions in LDL-C were achieved with rosuvastatin compared with equal doses of atorvastatin, enabling more patients with Type 2 diabetes to achieve European LDL-C goals.", "Although statin-treatment during the acute phase of unstable coronary syndromes improve the outcome their effects on thrombosis/fibrinolysis system in normocholesterolemic patients admitted with unstable angina remain obscure. We assessed the effects of short-term atorvastatin treatment on thrombotic/fibrinolysis markers in normocholesterolemic in patients with unstable angina.\n Forty-five patients with unstable angina were allocated into two groups to receive atorvastatin 10 mg/day (n = 24) or no statin (n = 21) for 6 weeks. Circulating levels of von Willebrand Factor (vWF), factor V (fV), protein C (prC), tissue plasminogen activator (tPA) and antithrombin III (ATIII) were measured by enzyme linked immunosorbent assay, by the patients admission and at the 1st and 6th week of the study.\n After 1 week of treatment, a significant increase of ATIII (p < 0.05), fV (p < 0.01) and vWF (p < 0.05) was found in the control group, but not in atorvastatin-treated group. Similarly, at 6 weeks after admission, plasma levels of ATIII were still significantly higher than at baseline in controls (p < 0.05), but not in atorvastatin-treated group. Plasma levels of PrtC were significantly increased in both controls (p < 0.01) and atorvastatin-treated patients (p < 0.05) at 1 week, while remained unaffected in atorvastatin-treated group at 6th week. There was no significant difference in the variations of plasma levels of tPA, PrtS and fVII between the two groups at 1 and 6 weeks after admission.\n In normocholesterolemic patients admitted with unstable angina the early administration of atorvastatin, significantly affects von Willebrand factor levels and the expression of liver-derived components of both thrombosis and fibrinolysis system.", "This study investigated the behavior of soluble intercellular adhesion molecule-1 (sICAM-1) and serum nitric oxide (NO) products, nitrite/nitrate (NO2-/NO3-), in subjects with primary hypercholesterolemia (HCh) without other risk factors and atherosclerosis. The effect of a short-term cholesterol-lowering treatment with atorvastatin, an HMG-CoA reductase inhibitor, on the levels of sICAM-1 and NO2-/NO3- were also investigated. After 4 weeks of placebo administration, 40 HCh (15 males and 25 females) were randomized in 2 groups: 20 subjects (atorvastatin group) received 10 mg/day of atorvastatin and the remaining 20 (placebo group) continued to take placebo. At baseline and after 4 and 12 weeks of atorvastatin or placebo administration, serum sICAM-1 and NO2-/NO3-levels were evaluated. The basal levels of these parameters were compared with those of 20 healthy subjects (C), matched for sex and age. Hypercholesterolemic subjects showed sICAM-1 and NO2-/NO3- basal values that were higher (331.7 +/- 60.3 ng/mL vs. 202.3 +/- 32.3 ng/mL, p<0.001) and lower (10.4 +/- 2.5 micromol/L vs. 20.7 +/- 4.4 micromol/L, p<0.01) than controls. No correlation between sICAM-1 or NO products and plasma cholesterol values was found, whereas there was an inverse correlation between sICAM-1 and NO2-/NO3- levels. Atorvastatin administration significantly decreased sICAM-1 and increased NO2-/NO3- levels, however these changes were not correlated with the reduction of plasma cholesterol. These data support the hypothesize that patients with HCh with no signs of arterial lesions, may have latent atherosclerosis, expressed as an increase of sICAM-1 and decrease in NO product levels. An improvement in the levels of these parameters after a short-time treatment with atorvastatin was also demonstrated.", "In a multinational trial (4522IL/0081), we assessed the effects of switching to low doses of rosuvastatin from commonly used doses of atorvastatin, simvastatin, and pravastatin on low-density lipoprotein cholesterol (LDL-C) goal achievement in high-risk patients.\n Hypercholesterolemic patients (n = 3140) with coronary heart disease, atherosclerosis, or type 2 diabetes were randomized to open-label rosuvastatin 10 mg, atorvastatin 10 or 20 mg, simvastatin 20 mg, or pravastatin 40 mg for 8 weeks. Patients either remained on these treatments for another 8 weeks or switched treatments from atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg to rosuvastatin 10 mg or from atorvastatin 20 mg to rosuvastatin 10 or 20 mg. The primary efficacy measure was the proportion of patients reaching the Joint European Societies' LDL-C goal (<116 mg/dL) at week 16. For measures of cholesterol goal achievement, treatment arms were compared using logistic-regression analysis.\n Significant improvement in LDL-C goal achievement was found for patients who switched to rosuvastatin 10 mg, compared with patients who remained on atorvastatin 10 mg (86% vs 80%, P <.05), simvastatin 20 mg (86% vs 72%, P <.0001), and pravastatin 40 mg (88% vs 66%, P <.0001), and between patients switched to rosuvastatin 20 mg and those who remained on atorvastatin 20 mg (90% vs 84%, P <.01). Similar results were found for achievement of the European combined LDL-C and total cholesterol goals and National Cholesterol Education Program Adult Treatment Panel III LDL-C goals. All statins were well tolerated over 16 weeks.\n We demonstrated that switching to a more efficacious statin is an effective strategy to improve lipid goal achievement in patients requiring lipid-lowering therapy.", "Heart failure has been associated with impaired endothelial function, increased inflammatory process and elevated oxidative stress status. Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and/or advanced atherosclerosis.\n To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and vascular cells adhesion molecule (sVCAM-1) in patients with ischemic heart failure.\n Thirty-eight male patients with ischemic cardiomyopathy were randomly divided into three groups and received either atorvastatin 10 mg/day (n = 14), a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day (n = 12), or no statin or antioxidant treatment (n=12, controls) for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration, respectively.\n RH% was significantly improved in both the atorvastatin-treated (p < 0.01) and atorvastatin plus vitamin E groups (p < 0.05), but the increase was significantly higher in the atorvastatin-treated group (p < 0.05). Serum levels of IL-6, TNF-alpha and sVCAM-1 were decreased in the atorvastatin-treated group (p < 0.05 for all), but remained unaffected in the other two groups (p = NS for all).\n Low dose atorvastatin treatment improves endothelial function and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure, an effect partly depressed by vitamin E.", "We hypothesized that atorvastatin (ATOR) treatment would reduce arterial stiffness in overweight and obese middle-aged and older adults. Twenty-six (11 men and 15 women) overweight or obese (body mass index: 31.6+/-0.7 kg/m(2)) middle-aged and older adults (age: 54+/-2 years) were randomly assigned to receive either ATOR (80 mg/d) or placebo for 12 weeks. Arterial stiffness (beta-stiffness and pulse wave velocity) was measured before and after the intervention. At baseline, the ATOR (n=16) and placebo (n=10) groups did not differ with respect to age, body mass index, blood pressure, serum lipid and lipoprotein concentrations, high-sensitivity C-reactive protein, indices of arterial stiffness, or compliance (all P>0.05). After the 12-week treatment period, the ATOR group experienced a 47% reduction in low-density lipoprotein cholesterol (149+/-6 to 80+/-8 mg/dL) and a 42% reduction in high-sensitivity C-reactive protein (3.6+/-0.8 to 2.1+/-0.5 mg/L; both P<0.05). In addition, beta-stiffness (9.4+/-0.6 to 7.6+/-0.5 U) and aortic pulse wave velocity (1096+/-36 to 932+/-32 cm/s), but not brachial pulse wave velocity, decreased (both P<0.05) with ATOR. In contrast, there were no significant changes in beta-stiffness (9.1+/-0.8 to 9.1+/-0.7 U) or aortic pulse wave velocity (1238+/-89 to 1191+/-90 cm/s; both P>0.05) in the placebo group. There were no relations between the reductions in arterial stiffness indices and any of the baseline cardiometabolic risk factors (all P>0.05). However, the reductions in arterial stiffness were correlated with the reduction in low-density lipoprotein cholesterol but not high-sensitivity C-reactive protein or any other cardiometabolic variables (all P<0.05). Taken together, these findings suggest that ATOR reduces arterial stiffness in overweight and obese middle-aged and older adults, and these favorable changes occur irrespective of baseline cardiometabolic risk factors.", "This study compared the efficacy and safety of co-administered ezetimibe + simvastatin with atorvastatin monotherapy in adults with hypercholesterolemia. Seven hundred eighty-eight patients were randomized 1:1:1 to 3 treatment groups; each group was force-titrated over four 6-week treatment periods: (1) 10 mg of atorvastatin as the initial dose was titrated to 20, 40, and 80 mg; (2) co-administration of 10 mg of ezetimibe and 10 mg of simvastatin (10/10 mg) was titrated to 10/20, 10/40, and 10/80 mg of ezetimibe + simvastatin; and (3) co-administration of 10/20 mg of ezetimibe + simvastatin was titrated to 10/40 mg (for 2 treatment periods) and 10/80 mg of ezetimibe + simvastatin. Key efficacy measures included percent changes in low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) from baseline to the ends of (1) treatment periods 1 and 2 (for LDL cholesterol) comparing co-administration of 10/20 mg and 10/10 mg of ezetimibe + simvastatin with 10 mg of atorvastatin and (2) treatment period 4 (for LDL cholesterol and HDL cholesterol) comparing co-administration of 10/80 mg of ezetimibe + simvastatin with 80 mg of atorvastatin. Baseline LDL and HDL cholesterol levels were comparable between treatment groups. At the end of treatment period 1, the mean decrease of LDL cholesterol was significantly (p </=0.001) greater for co-administration of 10/10 mg and 10/20 mg of ezetimibe + simvastatin than for 10 mg of atorvastatin. At the end of treatment period 4 and after comparing maximum doses, co-administration of 10/80 mg of ezetimibe + simvastatin was superior to 80 mg of atorvastatin in the percent LDL cholesterol decrease (-59.4% vs -52.5%, p <0.001) and HDL cholesterol increase (12.3% vs 6.5%; p <0.001). All treatments were well tolerated. Thus, a greater LDL cholesterol decrease and HDL cholesterol increase were attained by treating patients with co-administration of ezetimibe and simvastatin than with atorvastatin.", "We studied effect of atorvastatin on secretory phospholipase A2 group IIA (sPLA2-IIA) in blood serum of patients with ischemic heart disease (IHD), lipid composition of low density lipoproteins (LDL) and process of modification of LDL induced by sPLA2-IIA in 20 patients taking 20 mg/day of atorvastatin for 3 months. In patients with initially high level of sPLA2-IIA ( > 8 mcg/l) its concentration significantly decreased. Amount of total cholesterol, triglyceride, lecithin, and lysolecithin remained unchanged, however in equimolar relations there occurred decrease of amount of total cholesterol and increase of cholesterol esters. At incubation of LDL, extracted from patient s plasma before initiation of the study, with human sPLA2-IIA from cardiac myxoma, 3.5 nmol of lysolecithin per 1 mg of LDL protein was formed while at incubation of LDL of same patients, extracted after 3 months of atorvastatin administration, amount of lysolecithin was 1.54 nmol/mg LDL protein. Thus atorvastatin therapy causes lowering of sPLA2-IIA in patients with initially high blood level of the enzyme and to a great extent precludes sPLA2-IIA induced LDL modification.", "Studies have suggested that raising low levels of high-density lipoprotein cholesterol (HDL-C) may be an important target for the prevention of coronary heart disease.\n To compare the ability of micronized fenofibrate and atorvastatin to increase plasma HDL-C levels.\n Multicentre, randomized open-label study. Settings. The study was conducted in 19 centres across the UK and Canada.\n One hundred and eighty-one patients were randomized and the full analysis set included 165 nondiabetic patients with low HDL-C (women <46 mg dL-1, i.e. 1.2 mmol L-1 and men <43 mg dL-1, i.e. 1.1 mmol L-1): 86 patients in the atorvastatin group and 79 patients in the micronized fenofibrate group. Interventions. Micronized fenofibrate (200 mg day-1, 87 patients) or atorvastatin (10 mg day-1, 94 patients) for a period of 12 weeks. Main outcome measures. Percent change in HDL-C levels.\n After 12 weeks of treatment, the mean percent change from baseline in HDL-C was significantly higher in the micronized fenofibrate group (13.3%) compared with the atorvastatin group (5.3%, P=0.0003). The magnitude of such relative change was inversely related to the baseline HDL-C levels only in the micronized fenofibrate group. Furthermore, in the fenofibrate treatment group, 50.9% of the patients (29 of 57 patients) with a baseline HDL-C <40 mg dL-1 achieved a plasma HDL-C level above 40 mg dL-1 after 12 weeks of treatment versus 27.9% of the patients (19 of 68 patients) in the atorvastatin group (P=0.01).\n On the basis of (1) the greater impact of fenofibrate than atorvastatin on HDL-C levels and (2) the greater proportion of dyslipidemic patients achieving HDL-C levels above 40 mg dL-1 with fenofibrate than atorvastatin, it is suggested that micronized fenofibrate should be considered as a good therapeutic option to treat dyslipidemic patients with low HDL-C and moderately elevated LDL-C concentrations.", "The effect of low-dose atorvastatin on various biomarkers was investigated in patients with type 2 diabetes complicated by hyperlipidemia. At 0 and 12 weeks in both the atorvastatin group (10 mg/d; n=17) and the no-drug group (n=10), high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein (MCP)-1, plasminogen activator inhibitor (PAI)-1, and fibrinogen were measured. At baseline, the entire group of diabetic patients (n=27) had significantly higher values of hsCRP and fibrinogen compared with those in age-matched healthy subjects (n=29): 0.801 (0.306, 1.760) vs 0.282 (0.143, 0.6505) mg/L, P=.0042; 329.1+/-55.0 vs 212.4+/-35.9 mg/dL, P<.0001, respectively. High-sensitivity C-reactive protein decreased significantly with atorvastatin treatment, from 0.801 (0.243, 1.865) to 0.308 (0.200, 0.804) mg/L (P=.0191). Although MCP-1, PAI-1, and fibrinogen did not decrease in the atorvastatin patients overall, the decrease of MCP-1 was significant in women (n=10; from 241.9+/-45.8 to 215.4+/-49.5 pg/mL, P=.0332). No correlation was found between changes in the serum lipid concentrations and changes in hsCRP, MCP-1, PAI-1, or fibrinogen in either the atorvastatin or the no-drug group. In conclusion, low-dose atorvastatin (10 mg/d) significantly decreased hsCRP in patients overall, and MCP-1 was also decreased in women. These findings suggest the possibility that atorvastatin provides an anti-inflammatory effect even at a low dose.", "Endothelial dysfunction is frequently found in diabetic subjects. This study was performed to investigate whether atorvastatin therapy was able to reverse endothelial dysfunction in type 2 diabetes and, if so, whether the effect was due to its antiinflammatory action. Eighty patients (baseline low density lipoprotein, 4.37 +/- 0.71 mmol/liter) were randomized to atorvastatin (10 mg daily for 3 months, followed by 20 mg daily for 3 months) or placebo in a double blind study. Endothelial function was assessed by high resolution vascular ultrasound, and high sensitivity C-reactive protein (CRP) was assessed by immunoturbidimetric assay. Diabetic patients had higher CRP (P < 0.01) than matched nondiabetic controls, and both endothelium-dependent and independent vasodilation were impaired (P < 0.01). Atorvastatin (10 and 20 mg) lowered plasma cholesterol by 32.9% and 38.0%, triglyceride by 15.4% and 23.1%, and low density lipoprotein by 43.4% and 50.1%, respectively. At 6 months, plasma CRP decreased in the atorvastatin group compared with baseline (P < 0.05). Endothelium-dependent vasodilation improved in the atorvastatin group compared with the placebo group (P < 0.05). The percent change in endothelium-dependent vasodilation at 6 months correlated with the percent change in CRP (r = -0.44; P < 0.05), but not with changes in plasma lipids. In conclusion, treatment with atorvastatin in type 2 diabetes led to a significant improvement in endothelium-dependent vasodilation, which might be partly related to its anti-inflammatory effect.", "Elevated plasma concentration of chylomicron remnants may be causally related to atherosclerosis in obesity. We examined the effect of atorvastatin on chylomicron remnant metabolism in 25 obese men with dyslipidaemia. A remnant-like emulsion labeled with cholesteryl [(13)C]oleate was injected intravenously into patients; the fractional catabolic rate (FCR) of the remnant-like emulsion was determined by measurement of (13)CO(2) in the breath and analyzed using compartmental modelling. Compared with placebo, atorvastatin significantly decreased the plasma concentrations of total cholesterol, triglycerides, LDL cholesterol, apolipoprotein B (apoB), and lathosterol (P < 0.001). ApoB-48 and remnant-like particle-cholesterol (RLP-C) both decreased significantly by 23% (P = 0.002) and 33% (P = 0.045), respectively. The FCR of the remnant-like emulsion increased significantly from 0.054 +/- 0.008 to 0.090 +/- 0.010 pools/h (P = 0.002). The decrease in RLP-C was associated with the decrease in plasma triglycerides (r = 0.750, P = 0.003). Furthermore, the change in FCR of remnant-like emulsions was inversely associated with the change in LDL-C (r = -0.575, P = 0.040), suggesting removal of LDL and chylomicron remnants by similar hepatic receptor pathways. We conclude that in obese subjects, inhibition of cholesterol synthesis with atorvastatin decreases the plasma concentrations of both LDL-C and triglyceride-rich remnants and that this may be partially due to an enhancement in hepatic clearance of these lipoproteins.", "The ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (LDL-C/HDL-C) is a reliable predictor of cardiovascular risk. Low HDL-C levels in patients with coronary artery disease are associated with a high risk for cardiovascular events.\n This study compared the effects of rosuvastatin and atorvastatin on the LDL-C/HDL-C.\n Patients aged 40-80 years with established cardiovascular disease and HDL-C < 1.0 mmol/L (< 40 mg/dL) entered as a 6-week dietary run-in period, before randomisation to open-label treatment with rosuvastatin 10 mg (n = 230) or atorvastatin 20 mg (n = 231) for 6 weeks. Doses were increased after 6 weeks to rosuvastatin 20 mg or atorvastatin 40 mg, and after 12 weeks to rosuvastatin 40 mg or atorvastatin 80 mg. Serum lipid parameters were measured at baseline and 6, 12 and 18 weeks.\n After 6 weeks of treatment, mean percentage change from baseline in LDL-C/HDL-C ratio was -47.0% in the rosuvastatin group and -41.9% in the atorvastatin group (p < 0.05 for between-group comparison). After 12 and 18 weeks of treatment, change from baseline was -53.0% and -57.3%, respectively, for rosucastatin, compared with -47.9% and -49.6%, respectively, for atorvastatin (p < 0.01 and p < 0.001, respectively, for between-group comparison). Rosuvastatin also reduced LDL-C, total cholesterol/HDL-C significantly more than atorvastatin at all three time points, and significantly improved total cholesterol/HDL-C and apolipoprotein B/A-I ratios.\n Rosuvastatin 10, 20 and 40 mg is significantly more effective than atorvastatin 20, 40 and 80 mg, respectively, in improving the LDL-C/HDL-C ratio in patients with cardiovascular disease and low HDL-C. Further studies are required to clarify the benefits of rosuvastatin for reduction of cardiovascular risk.", "Hypercholesterolaemia is a risk factor for coronary heart disease (CHD). Clinical studies have shown that lowering elevated serum total cholesterol (TC) levels, and particularly low density lipoprotein-cholesterol (LDL-C) levels, reduces the frequency of coronary morbidity and deaths, whereas high serum levels of high density lipoprotein-cholesterol (HDL-C) protect against CHD. Policosanol is a cholesterol-lowering drug purified from sugar cane wax with a therapeutic dosage range from 5-20 mg/day. Atorvastatin is an HMG-CoA reductase inhibitor which across its dosage range (10-80 mg/day) has shown significantly greater lipid-lowering effects than all previously marketed statins.\n This study was undertaken to compare the efficacy and tolerability of policosanol with atorvastatin in older patients with type II hypercholesterolaemia.\n This randomised, single-blind, parallel-group study was conducted in older patients (60-80 years) with type II hypercholesterolaemia. After 4 weeks on a cholesterol-lowering diet, 75 patients were randomised to policosanol or atorvastatin 10mg tablets taken once daily with the evening meal for 8 weeks. An interim and final check-up were performed at 4 and 8 weeks, respectively, after treatment was initiated.\n At 4 (p < 0.0001) and 8 (p < 0.00001) weeks, policosanol 10 mg/day significantly lowered serum LDL-C levels by 17.5 and 23.1%, respectively compared with baseline; corresponding values for atorvastatin were 28.4 and 29.8%. At study completion, policosanol significantly (p < 0.0001) reduced serum TC (16.4%), LDL-C/HDL-C ratio (25.5%) and TC/HDL-C ratio (19.3%), as well as (p < 0.001) triglyceride levels (15.4%). Atorvastatin significantly (p < 0.0001) decreased serum TC (22.6%), LDL-C/HDL-C (26.2%) and TC/HDL-C (19.8%) ratios, as well as (p < 0.001) triglyceride levels (15.5%). Atorvastatin was significantly more effective than policosanol in reducing LDL-C and TC, but similar in reducing both atherogenic ratios and triglyceride levels. Policosanol, but not atorvastatin, significantly (p < 0.05) increased serum HDL-C levels by 5.3%. Both treatments were well tolerated. At study completion, atorvastatin mildly, but significantly (p < 0.05) increased creatine phosphokinase (CPK) and creatinine, whereas policosanol significantly reduced AST and glucose (p < 0.01) and CPK (p < 0.05) levels. All individual values, however, remained within normal limits. Three atorvastatin but no policosanol patients withdrew from the study because of adverse events: muscle cramps (1 patient), gastritis (1 patient) and uncontrolled hypertension, abdominal pain and myalgia (1 patient). Overall, no policosanol and seven atorvastatin patients (18.9%) reported a total of nine mild or moderate adverse events during the study (p < 0.01).\n This study shows that policosanol (10 mg/day) administered for 8 weeks was less effective than atorvastatin (10 mg/day) in reducing serum LDL-C and TC levels in older patients with type II hypercholesterolaemia. Policosanol, but not atorvastatin, however, significantly increased serum HDL-C levels, whereas both drugs similarly reduced atherogenic ratios and serum triglycerides. Policosanol was better tolerated than atorvastatin as revealed by patient withdrawal analysis and overall frequency of adverse events. Nevertheless, further studies must be conducted in larger sample sizes and using dose-titration methods to achieve target lipid levels in order to reach wider conclusions.", "Hypertension is considered resistant if blood pressure cannot be reduced to <140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP goals.\n To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia.\n Forty-eight hyperlipidemic subjects with RH (office systolic BP >140 mmHg and/or office diastolic BP >90 mmHg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17)--mean 24 hour SBP 150.6 +/- 5.2 mmHg, DBP 86.1 +/- 3.3 mmHg, low density lipoprotein 158.1 +/- 24.5 mg/dl--received vitamin C 500 mg per day; Group ATR (n = 15)--mean 24 hour SBP 153.1 +/- 4.8 mmHg, DBP 87.1 +/- 6.7 mmHg, LDL 162.6 +/- 13.6 mg/dl--received atorvastatin 20 mg/day; and Group PLA (n = 16)--mean 24 hour SBP 151.1 +/- 7.4 mmHg, DBP 84.8 +/- 5.9 mmHg, LDL 156.7 +/- 26.1 mg/dl--received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks.\n In the ATR group there were significant reductions of SBP (deltaSBP1-2: 13.7 +/- 5.6 mmHg, P 0.001), DBP (deltaDBP1-2: 7.8 +/- 5.7 mmHg, P 0.01), LDL (deltaLDL1-2: 67.7 +/- 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD (deltaFMD2-1: 4.2 +/- 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups.\n In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods.", "The major beneficial effect of statins- reducing the risk for coronary events-has primarily been ascribed to reductions in low-density lipoprotein cholesterol (LDL-C) but may in part be related to a direct antiinflammatory action (ie, decreased high-sensitivity C-reactive protein [hs-CRP] concentration).\n The objectives of this CAP (Comparative Atorvastatin Pleiotropic Effects) study were to compare the effects of low- versus high-dose atorvastatin on hs-CRP concentrations and to determine the relationship between changes in LDL-C and hs-CRP concentrations in patients with coronary artery disease (CAD), low-grade inflammation, and normal lipoprotein concentrations.\n This multicenter, prospective, randomized, double-blind, double-dummy study was conducted at 65 centers across Canada and Europe. Patients with documented CAD, low-grade inflammation (hs-CRP concentration, 1.5-15.0 mg/L), and a normal-range lipid profile (LDL-C concentration, 1.29-3.87 mmol/L [50-150 mg/dL]; triglyceride [TG] concentration, <4.56 mmol/L [<400 mg/dL]) were randomly assigned to receive 26-week double-blind treatment with atorvastatin 10 or 80 mg QD. Investigators were to aim for the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C target of <2.59 mmol/L (<100 mg/dL). The primary end point was the percentage change from baseline in hs-CRP, as measured at baseline and weeks 5, 13, and 26 using high-sensitivity, latex microparticle-enhanced immunoturbidimetric assay. Changes from baseline in LDL-C, as measured directly in serum at the same time points, were also calculated. The secondary efficacy variables included the percentage changes from baseline in lipid parameters (LDL-C, high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], TG, apolipoprotein B, non-HDL-C, and TC:HDL-C ratio) at 5, 13, and 26 weeks of treatment. Tolerability was assessed using physical examination, including vital sign measurement, and laboratory analyses.\n A total of 339 patients were enrolled (283 men, 56 women; mean age, 62.5 years; weight, 81.3 kg; 10-mg/d group, 170 patients; 80-mg/d group, 169). No significant differences in baseline demographic or clinical data were found between the 2 treatment arms. In the 10-mg group, hs-CRP was decreased by 25.0% at 5 weeks and remained stable thereafter (%Delta at week 26, -24.3%; P < 0.01). In the 80-mg group, hs-CRP was decreased by 36.4% at 5 weeks and continued to be decreased over the study period (%Delta, -57.1% at week 26; P < 0.001 vs baseline). At 5 weeks, LDL-C was decreased by 35.9% in the 10-mg group and by 52.7% in the 80-mg group (P < 0.001 between groups) and remained stable thereafter (%Delta at week 26, -34.8% and -51.3%, respectively; P < 0.001 between groups). The NCEP ATP III LDL-C target of <2.59 mmol/L (<100 mg/dL) was reached in 77.1% of patients treated with atorvastatin 10 mg and 92.3% of those treated with 80 mg (P < 0.001). Dual targets of hs-CRP <2 mg/L and LDL-C <1.81 mmol/L (<70 mg/dL) were reached in a significantly greater proportion of patients in the 80-mg group compared with the 10-mg group (55.6% vs 13.5%; P < 0.001). The decrease in hs-CRP was largely independent of baseline LDL-C and change in LDL-C. Two serious adverse events were reported by the investigator as treatment related: acute hepatitis in the 10-mg group and intrahepatic cholestasis in the 80-mg group, in 2 patients with multiple comorbidities. Two deaths occurred during the study, both in the atorvastatin 80-mg group (1, myocardial infarction; 1, sudden death), neither of which was deemed treatment related by the investigator.\n In these patients with documented CAD, evidence of low-grade inflammation, and normal range lipid profiles, the effects of atorvastatin on changes in hs-CRP were dose dependent, with the high dose (80 mg) being associated with significantly greater reductions in hs-CRP concentrations. Both doses were associated with a significant and progressive decline in hs-CRP largely independent of changes in LDL-C, HDL-C, and TG. Clinical Trials Identification Number: NCT00163202.", "Although insulin resistance (IR) is present in non-diabetic subjects, it is unknown whether IR affects statin treatment. We assessed the relationship between IR and the changes of lipid profile in patients with hyperlipidemia treated by atorvastatin.\n Forty-four non-diabetic patients were included. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. We used the value of 2.5 as the threshold for IR.\n High-density lipoprotein (HDL) cholesterol at baseline was lower and triglyceride (TG) at baseline was higher in the IR group than in the nonIR group (p < 0.05). Changes in all lipid measurements did not differ between the two groups. HOMA-IR was correlated with HDL cholesterol at baseline and at follow-up and correlated with TG at baseline and at follow-up (r = -0.40, r = -0.53, r = 0.38, r = 0.35, p < 0.01, respectively). However, HOMA-IR did not associate with changes in total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, and TG.\n The IR did not affect the degree of reduction in cholesterol by atorvastatin in non-diabetic subjects. The IR may influence hypertriglyceridemia greater than the effect of atorvastatin in non-diabetic subjects.", "In this prospective study, we found beneficial short-term effects from atorvastatin therapy, including effects on low-density lipoprotein subfractions and remnant-like lipoprotein particle cholesterol, antioxidant effects, and alterations in endothelial function that may be important in early benefit from statin therapy; some effects would support much earlier benefit than previously reported. We also found long-term effects of atorvastatin, including decreased plasminogen activator inhibitor type-1 and additional significant alterations in low-density lipoprotein subfractions and endothelial function, supporting benefits from continuous long-term atorvastatin therapy beyond early reversal of hypercholesterolemia.", "Human serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low-density lipoprotein (LDL); therefore, it may protect against atherosclerosis. Changes in the ratio of high-density lipoprotein (HDL) subfractions may alter the stability and the antioxidant capacity of PON1. The aim of the study was to examine the effect of atorvastatin treatment on the distribution of HDL subfractions, LDL size, cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and PON1 activity. In all, 33 patients with type IIa and IIb hypercholesterolemia were involved in the study. LDL sizes and HDL subfractions were determined by gradient gel electrophoresis. CETP, LCAT, and PON1 activities were measured spectrophotometrically. Three months of treatment with atorvastatin 20 mg daily significantly increased the HDL3 (+8.13%) and decreased the HDL2a and HDL2b subfractions (-1.57% and -6.55%, respectively). The mean LDL size was significantly increased (+3.29%). The level of oxidized LDL was significantly decreased (-46.0%). The PON1 activity was augmented by the atorvastatin treatment (+5.0%). The CETP activity positively correlated with the HDL2b level and negatively correlated with the HDL3 and HDL2a levels. Atorvastatin alters the HDL subfractions, which may improve its antiatherogenic effect via enhancement of the PON1 activity.", "Inflammation contributes to the pathogenesis of coronary heart disease and elevated serum levels of C-reactive protein (CRP) are independently associated with increased coronary risk. This study assessed whether there were differences in the effects on CRP and high-density lipoprotein (HDL) cholesterol levels among patients treated with three common statins. In a prospective, observational study, 80 dyslipidemic adults without evidence of cardiovascular disease were treated with 10 mg atorvastatin (A), 20 mg simvastatin (S), or 40 mg pravastatin (P) daily. CRP and lipid profiles were assayed before and after 12 weeks of therapy; in 21 patients, CRP levels were also measured after 1 and 4 weeks. The three treatment groups experienced comparable reductions in CRP (A: 33%, S: 42%, and P: 30%) and statistically insignificant changes in HDL cholesterol levels. CRP began to decrease after 1 week of treatment, and decreased further at 4 and 12 weeks of therapy. The change in the log-transformed CRP concentration correlated with the change in the log-transformed LDL cholesterol concentration. Subjects had similar baseline CRP levels, lipid profiles, and coronary risk factors. The authors conclude that at doses achieving similar reductions in LDL cholesterol, the three statins were associated with comparable decreases in CRP without significant changes in HDL cholesterol levels. The correlation between the reductions in CRP and LDL cholesterol differs from the findings of other published studies, and should prompt further investigation of the mechanism by which statins reduce CRP.", "The purpose of this study is to determine plasma fibronectin level and its relationships with plasma lipids, lipoproteins and C-reactive protein (CRP) levels in patients with dyslipidaemia during lipid-lowering therapy.\n Plasma levels of fibronectin, CRP, fibrinogen, lipids and lipoproteins in 38 patients with dyslipidaemia were determined before and after lipid-lowering therapy by using atorvastatin, 10 mg/day.\n After lipid-lowering therapy, serum levels of fibronectin and CRP were found to be significantly decreased by 30.4% and 43.6%, respectively, while fibrinogen levels were increased 11.7% in patients with dyslipidaemia. Before the treatment, fibronectin was found to be positively correlated with CRP and total cholesterol (r=0.38, p<0.05 and r=0.33, p<0.05, respectively) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (r=-0.42, p<0.01) in patients with dyslipidaemia. High fibronectin levels (0.57 +/- 0.17 g/l) were found in patients with HDL-C below 35 mg/dl (0.57 +/- 0.09 g/l), compared to patients with HDL-C above 35 mg/dl (0.45 +/- 0.11 g/l). During the lipid-lowering therapy, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and apo B levels were reduced while HDL-C and apo AI levels were increased.\n It was found that plasma fibronectin and CRP levels were decreased by lipid lowering therapy. Plasma fibronectin levels were associated with lipids, lipoproteins, CRP levels before treatment and these relationships disappeared after treatment. Consequently, it was suggested that reduction of plasma fibronectin levels, together with lipids and loss of its relationship with CRP, may play a role on the antiatherogenic effects of lipid-lowering therapy.", "The lipid-lowering effects of rosuvastatin and atorvastatin were determined across their dose ranges in a 6-week, randomized, double-blind trial. Three hundred seventy-four hypercholesterolemic patients with fasting low-density lipoprotein (LDL) cholesterol > or =160 but <250 mg/dl (> or =4.14 but <6.47 mmol/L) and fasting triglycerides <400 mg/dl (<4.52 mmol/L) and without active arterial disease within 3 months of entry received once-daily rosuvastatin (5, 10, 20, 40, or 80 mg [n = 209]) or atorvastatin (10, 20, 40, or 80 mg [n = 165]). The percentage decrease in plasma LDL cholesterol versus dose was log-linear for each drug, ranging from -46.6% to -61.9% for rosuvastatin 10 and 80 mg, compared with -38.2% to -53.5% for atorvastatin 10 and 80 mg. The dose curve for rosuvastatin yielded an 8.4% greater decrease in LDL cholesterol compared with atorvastatin at any given dose (p <0.001). Similarly greater decreases were observed for rosuvastatin across the dose range in total cholesterol (-4.9%), non-high-density lipoprotein (non-HDL) cholesterol (-7.0%), apolipoprotein B (-6.3%), and related ratios versus atorvastatin (all p <0.001). Because dose responses for HDL cholesterol, triglycerides, and apolipoprotein A-I were non-log-linear and nonparallel between the 2 drugs, percentage changes from baseline were compared at each dose. Significantly greater increases for rosuvastatin compared with atorvastatin were observed for HDL cholesterol at 40 and 80 mg, and for apolipoprotein A-I at 80 mg. Significantly greater triglyceride decreases were seen at 80 mg with atorvastatin over rosuvastatin. Both rosuvastatin and atorvastatin were well tolerated over 6 weeks.", "This 6-week, double-blind clinical trial evaluated lipid parameter responses to different dosages of atorvastatin in patients with primary hypercholesterolemia. Atorvastatin is a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor under development. After completing an 8-week placebo-baseline dietary phase, 81 patients were randomly assigned to receive either placebo or 2.5, 5, 10, 20, 40, or 80 mg atorvastatin once daily for 6 weeks. Plasma LDL cholesterol reductions from baseline were dose related, with 25% to 61% reduction from the minimum dose to the maximum dose of 80 mg atorvastatin once a day. Plasma total cholesterol and apo B reductions were also dose related. Previously, reductions in LDL cholesterol of the magnitude observed in this study have been seen only with combination drug therapy. In this study, atorvastatin was well tolerated by hyperlipidemic patients, had an acceptable safety profile, and provided greater reduction in cholesterol than other previously reported HMG-CoA reductase inhibitors.", "Statin therapy has been found to produce substantial reductions in low-density lipoprotein cholesterol (LDL-C) levels, resulting in a reduced risk for cardiovascular events. Recently, research interest has focused on modification of high-density lipoprotein cholesterol (HDL-C) levels for the potential prevention of cardiovascular events. The effects of pitavastatin and atorvastatin on HDL-C have not been directly compared.\n This study compared the effects of pitavastatin and atorvastatin on HDL-C and other lipids and glucose metabolism in Japanese patients with elevated LDL-C levels and glucose intolerance. The tolerability of the 2 treatments was also compared.\n This was a multicenter, open-label, parallel-group trial. Patients with LDL-C levels>or=140 mg/dL and glucose intolerance (defined according to Japanese criteria for borderline diabetes and World Health Organization criteria for impaired fasting glucose and impaired glucose tolerance) were randomly assigned to receive either pitavastatin 2 mg/d or atorvastatin 10 mg/d for 52 weeks. Levels of serum lipids and lipoproteins and measures of glucose metabolism (fasting insulin, fasting glucose, glycosylated hemoglobin, and homeostasis model assessment for insulin resistance) were obtained at baseline and at 8, 26, and 52 weeks of treatment. The effect of study drug on glucose metabolism was evaluated as a tolerability outcome. Tolerability was further assessed based on adverse events, either spontaneously reported or elicited by questioning; physical examination findings; and clinical laboratory test results. Study physicians rated the relationship of adverse events to study medication as unrelated, suspected, or probable.\n Two hundred seven patients were enrolled in the study, and efficacy was evaluated in 173 patients (88 pitavastatin, 85 atorvastatin). Thirty-four patients were excluded for reasons including failure to start medication or lack of >or=6 months of follow-up. Women accounted for 62% (108/173) of the evaluable population, which had a mean age of 63.3 years and a mean weight of 63.0 kg; 89% (154/173) had diabetes mellitus. The percent change in HDL-C levels was significantly greater in the pitavastatin group compared with the atorvastatin group (8.2 vs 2.9, respectively; P=0.031), as was the percent change in apolipoprotein (Apo) A-I (5.1 vs 0.6; P=0.019). The percent change in LDL-C levels was significantly lower with atorvastatin compared with pitavastatin (-40.1 vs -33.0, respectively; P=0.002), as were the percent changes in non-HDL-C (-37.4 vs -31.1; P=0.004), Apo B (-35.1 vs -28.2; P<0.001), and Apo E (-28.1 vs -17.8; P<0.001). The significant results for these parameters were unchanged when all 189 subjects who received>or=1 dose of study medication were included in the analysis, using last-value-carried-forward methodology. There were no significant differences between treatments with respect to the measures of glucose metabolism. Both statins appeared to be well tolerated. Adverse events occurred in 9% (9/96) of the pitavastatin group and 14% (13/93) of the atorvastatin group (P=NS). Two patients in the pitavastatin group and none in the atorvastatin group had an alanine aminotransferase value>3 times the upper limit of normal (P=NS).\n In these patients with elevated LDL-C levels and glucose intolerance, 52 weeks of treatment with pitavastatin 2 mg/d was associated with significantly greater increases in HDL-C and Apo A-I levels than atorvastatin 10 mg/d. Both treatments were well tolerated.", "Adherence to evidence-based guidelines for the secondary prevention of coronary heart disease (CHD) has been shown to be poor in a number of surveys. In this open-label, non-comparative 17-week trial, 399 patients with existing CHD and LDL cholesterol concentration > 3.4 mmol/l (130 mg/dl) were treated with atorvastatin 10 mg daily. After 5 weeks, the dose of atorvastatin was adjusted according to a patient's LDL cholesterol level. Of the 379 patients remaining in the study after five weeks of treatment, dose titration was not required for 355 patients (94%) who had reached the target LDL cholesterol of < or = 3.4 mmol/l. Of the 23 patients titrated to higher doses, 11 achieved the target LDL cholesterol after treatment for 17 weeks. Atorvastatin was well tolerated during the course of the study. Achieving LDL cholesterol targets without the need for dose titration simplifies clinical management and should encourage better adherence to evidence-based recommendations for secondary prevention of CHD.", "Aggressive treatment of low-density lipoprotein cholesterol (LDL-C) fails to prevent most cardiovascular (CV) events. Concurrent treatment of LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) should be considered in patients with dyslipidemia.\n The efficacy and safety of a proprietary niacin extended-release and simvastatin (NER/S) combination were compared to atorvastatin monotherapy in a multicenter, Prospective, Randomized (3:2), Open-label, Blinded Endpoint (PROBE) study.\n Following ≥4 weeks without lipid-modifying therapies, 193 patients with dyslipidemia were treated with NER/S (n = 114; 1000/40 mg/day, weeks 1 to 4; 2000/40 mg/day weeks 5 to 12) or atorvastatin (n = 79; 40 mg/day, weeks 1 to 12).\n Compared to atorvastatin, NER/S had a larger beneficial effect on HDL-C (primary end point: 30.1 ± 2.3% and 9.4 ± 2.6%, respectively; P <.001), TG (P = .02), and lipoprotein(a) (Lp[a]; P <.001), and similar effects on LDL-C and non-HDL-C. Two-thirds of patients treated with NER/S concurrently attained LDL-C (CV risk-adjusted goals), HDL-C (≥40 mg/dL), and TG (<150 mg/dL) targets, compared to one-third of patients treated with atorvastatin (P <.001). Flushing was the most common treatment-emergent adverse event (TEAE) (67.5% NER/S and 10.1% atorvastatin; P <.001). Seventy-five percent of flushing episodes were mild to moderate. More patients treated with NER/S discontinued due to TEAEs (21.1% and 3.8%; P <.001); the most common TEAE was flushing.\n Compared to atorvastatin, NER/S provided superior improvements in HDL-C, TG, and Lp(a) and comparable improvements in non-HDL-C and LDL-C. Treatment with NER/S should be considered for patients with dyslipidemia requiring comprehensive lipid control.", "In a 24-week, open-label, randomized, parallel-group study, we compared the efficacy and metabolic effects, beyond low density lipoprotein cholesterol (LDL-C)-lowering, of atorvastatin (ATV) and rosuvastatin (RSV) in cardiovascular disease-free subjects with primary hyperlipidaemia, treated to an LDL-C target (130 mg/dL).\n After a 6-week dietary lead-in period, patients were randomized to RSV 10 mg/day (n = 60) or ATV 20 mg/day (n = 60). After 6 weeks on treatment the dose of the statin was increased (to RSV 20 mg/day or ATV 40 mg/day) if the treatment goal was not achieved. A control group of healthy volunteers (n = 60) was also included for the validation of baseline serum and urinary laboratory parameters. The primary outcome was the percentage of patients reaching the LDL-C goal; secondary outcomes were changes in lipid and non-lipid metabolic parameters.\n A total of 45 patients (75.0%) in the RSV-treated group and 43 (71.7%) in the ATV-treated group achieved the treatment target at the initial dose. Both regimens were generally well tolerated and there were no withdrawals due to treatment-related serious adverse events. Similar significant reductions in total cholesterol, LDL-C, apolipoprotein (apo) B, triglycerides, apoB/apoA1 ratio, fibrinogen and high-sensitivity C-reactive protein levels were seen. RSV had a significant high density lipoprotein cholesterol (HDL-C)-raising effect and showed a trend towards increasing apoA1 levels. Glycaemic control and renal function parameters were not influenced by statin therapy. ATV, but not RSV, showed a significant hypouricaemic effect.\n RSV and ATV were equally efficacious in achieving LDL-C treatment goals in patients with primary hyperlipidaemia at the initial dose and following dose titration. RSV seems to have a significantly higher HDL-C-raising effect, while ATV lowers serum uric acid levels.", "The primary objective of this 6-week, parallel-group, open-label, randomized, multicenter trial was to compare rosuvastatin with atorvastatin, pravastatin, and simvastatin across dose ranges for reduction of low-density lipoprotein (LDL) cholesterol. Secondary objectives included comparing rosuvastatin with comparators for other lipid modifications and achievement of National Cholesterol Education Program Adult Treatment Panel III and Joint European Task Force LDL cholesterol goals. After a dietary lead-in period, 2,431 adults with hypercholesterolemia (LDL cholesterol > or =160 and <250 mg/dl; triglycerides <400 mg/dl) were randomized to treatment with rosuvastatin 10, 20, 40, or 80 mg; atorvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; or pravastatin 10, 20, or 40 mg. At 6 weeks, across-dose analyses showed that rosuvastatin 10 to 80 mg reduced LDL cholesterol by a mean of 8.2% more than atorvastatin 10 to 80 mg, 26% more than pravastatin 10 to 40 mg, and 12% to 18% more than simvastatin 10 to 80 mg (all p <0.001). Mean percent changes in high-density lipoprotein cholesterol in the rosuvastatin groups were +7.7% to +9.6% compared with +2.1% to +6.8% in all other groups. Across dose ranges, rosuvastatin reduced total cholesterol significantly more (p <0.001) than all comparators and triglycerides significantly more (p <0.001) than simvastatin and pravastatin. Adult Treatment Panel III LDL cholesterol goals were achieved by 82% to 89% of patients treated with rosuvastatin 10 to 40 mg compared with 69% to 85% of patients treated with atorvastatin 10 to 80 mg; the European LDL cholesterol goal of <3.0 mmol/L was achieved by 79% to 92% in rosuvastatin groups compared with 52% to 81% in atorvastatin groups. Drug tolerability was similar across treatments.", "To assess the lipid-lowering effects and safety of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia.\n We performed a randomized, open-label, parallel-design, active-controlled, study in eight centers in the United States. We enrolled 108 patients with total cholesterol (TC) of > or =200 mg/dL, serum triglycerides (TG) > or =200 and < or =800 mg/dL, and apolipoprotein B (apo B) > or =110 mg/dL. Patients were randomly assigned to receive atorvastatin 10 mg once daily (n=55) or immediate-release niacin 1 g three times daily for 12 weeks (n=53). Patients were stratified based on low-density lipoprotein cholesterol (LDL-C): Patients with LDL-C > or =135 mg/dL were considered to have combined hyperlipidemia and patients with LDL-C <135 mg/dL were considered to have isolated hypertriglyceridemia. The primary outcome measure was percent change from baseline in LDL-C. Other lipid levels were evaluated as secondary parameters.\n Atorvastatin reduced LDL-C 30% and TC 26% from baseline, and increased high-density lipoprotein cholesterol (HDL-C) 4%. Total TG were reduced 17%. Niacin reduced LDL-C 2%, TC 7%, increased HDL-C 25%, and reduced total TG 29% from baseline. There was a significant difference in LDL-C reduction, the primary efficacy parameter, between the two treatment groups (P <0.05, favoring atorvastatin), as well as a significant difference in the improvement in HDL-C (P <0.05, favoring niacin). The effect of atorvastatin was relatively consistent between patients with combined hyperlipidemia and isolated hypertriglyceridemia, whereas there was more variability between these strata in the niacin treatment group. Atorvastatin was better tolerated than niacin.\n Atorvastatin may allow patients with combined hyperlipidemia to be treated with monotherapy and offers an efficacious and well-tolerated alternative to niacin for the treatment of patients with isolated hypertriglyceridemia.", "Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of serum LDL-cholesterol (LDL-C) levels. PCSK9 is secreted by the liver into the plasma and binds the hepatic LDL receptor (LDLR), causing its subsequent degradation. We first demonstrated that a moderate dose of atorvastatin (40 mg) increases PCSK9 serum levels, suggesting why increasing statin doses may have diminished efficacy with regard to further LDL-C lowering. Since that initial observation, at least two other groups have reported statin-induced PCSK9 increases. To date, no analysis of the effect of high-dose atorvastatin (80 mg) on PCSK9 over time has been conducted. Therefore, we studied the time course of atorvastatin (80 mg) in human subjects. We measured PCSK9 and lipid levels during a 2-week lead-in baseline period and every 4 weeks thereafter for 16 weeks. We observed that atorvastatin (80 mg) caused a rapid 47% increase in serum PCSK9 at 4 weeks that was sustained throughout 16 weeks of dosing. Importantly, while PCSK9 levels were highly correlated with total cholesterol (TC), LDL-C, and triglyceride (TG) levels at baseline, atorvastatin (80 mg) completely abolished all of these correlations. Together, these results further suggest an explanation for why increasing doses of statins fail to achieve proportional LDL-C lowering.", "Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti-inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation (NCT00252967).\n In a randomized, double-blinded, placebo-controlled trial, patients with atrial fibrillation/flutter (AF) were randomized to receive either atorvastatin 80 mg (n = 33) or placebo (n = 31) before CV. Treatment was continued for 12 months or until AF recurred. Serum oxidative stress markers (ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, isoprostanes) and inflammatory markers (high-sensitivity C- reactive protein [hs-CRP], interleukin-6 [IL-6], interleukin-1β[IL-1β], tumor necrosis factor alpha [TNFα]) were measured at baseline and on follow-up. AF recurred in 22 (66.7%) of atorvastatin and 26 (83.9%) of placebo group (P = 0.2). The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 (95% CI: 0.98-1.01, P = 0.3). There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates (median [IR]: 29 [2-145] days versus 22 [7-70] days, P = 0.9). Although no significant effect was seen on oxidative stress, 2 of 4 inflammatory markers, IL-6 (adjusted OR: 0.59, 95% CI: 0.35-0.97, P = 0.04) and hs-CRP (adjusted OR: 0.59, 95% CI: 0.37-0.95, P = 0.03) were significantly lowered with atorvastatin. Cholesterol levels significantly decreased with atorvastatin (P = 0.03).\n High-dose atorvastatin did not reduce the recurrence of AF after CV. It reduced selective markers of inflammation without affecting systemic oxidative stress. Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress.\n © 2010 Wiley Periodicals, Inc.", "Apolipoprotein B has been shown to be a better predictor of coronary heart disease than low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol may also be a better parameter for coronary heart disease risk assessment and as a target for therapy. Data from the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) were used to assess the correlation between lipid and apolipoprotein B levels before and after lipid-lowering therapy and to examine the effects of 5 hydroxymethylglutaryl coenzyme A reductase inhibitors on lipids and apolipoprotein B. The 54-week study randomized 3,916 hypercholesterolemic patients to atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin, initiated at recommended starting doses with titrations as needed at weeks 6, 12, and 18 to achieve National Cholesterol Education Program LDL targets. Compared with LDL cholesterol, non-HDL cholesterol correlated better with apolipoprotein B levels at baseline (r = 0.914, p <0.0001) and at week 54 (r = 0.938, p <0.0001), and the correlation was strong across all baseline triglyceride strata. At starting doses, atorvastatin (10 mg) lowered non-HDL cholesterol by 33.3% compared with 26.6% with simvastatin (10 mg), 24.1% with lovastatin (20 mg), 17.2% with fluvastatin (20 mg), and 17.0% with pravastatin (10 mg). Atorvastatin also provided greater reductions in non-HDL cholesterol after dose titration, and a greater percentage of patients taking atorvastatin achieved non-HDL cholesterol targets. Baseline triglyceride did not affect non-HDL cholesterol reductions with any of the 5 hydroxymethylglutaryl coenzyme A reductase inhibitors. Fewer patients achieved non-HDL cholesterol targets than LDL cholesterol targets, particularly among high-risk patients, implying that if non-HDL cholesterol was used as a target for treatment, more patients would need to be treated more aggressively than National Cholesterol Education Program guidelines require.", "Apart from lowering lipid levels, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) produce many other favorable effects that contribute to their clinical efficacy in the primary and secondary prevention of cardiovascular diseases. The aim of this study was to assess the effect of 30-day atorvastatin treatment on major hemostatic risk factors (fibrinogen, PAI-1 levels, factor VII coagulant activity) in patients with primary hypercholesterolemia. We studied 18 hypercholesterolemic patients and 12 matched control subjects. Compared to the control subjects, hypercholesterolemic patients exhibited increased plasma PAI-1 levels and factor VII activity. Atorvastatin (20 mg/d) not only decreased total cholesterol, LDL cholesterol and oxidized LDL, but also reduced PAI-1 levels and factor VII activity and tended to decrease fibrinogen levels. The hemostatic effects of atorvastatin did not correlate with its lipid-lowering potential. Our study is the first to show that atorvastatin may exhibit a quick, beneficial and multidirectional nonlipid-related effect on hemostasis.", "The aim of this study was to compare the effect of 30-day treatment with atorvastatin and fenofibrate on monocyte release and plasma levels of monocyte chemoattractant protein-1 (MCP-1). We studied 52 atherosclerotic patients with primary mixed dyslipidemia and 16 age-, sex-, and weight-matched control subjects with asymptomatic atherosclerosis. Dyslipidemic patients enrolled into the study were randomly divided into three groups, simultaneously treated with atorvastatin (20 mg/d, n = 18), fenofibrate (267 mg/d, n = 16), or placebo (n = 18). Plasma lipid-profile and content of MCP-1, and monocyte release of this chemokine were measured at baseline and after 30 days of therapy. Compared with the control subjects, dyslipidemic patients exhibited the increased plasma levels and monocyte MCP-1 release. Atorvastatin and fenofibrate not only improved lipid profile but also decreased monocyte secretion of this chemokine. Moreover, hypolipemic agents slightly reduced its plasma levels. MCP-1-lowering effect of atorvastatin and fenofibrate did not correlate with the lipid-lowering potential of these agents. Our results suggest that atorvastatin and fenofibrate produce their antiinflammatory effect partially via inhibiting monocyte release of MCP-1. The treatment-induced reduction in its secretion may contribute to the clinical effectiveness of statins and fibrates in the therapy for atherosclerosis and other chronic fibroproliferative diseases.", "nan", "The efficacy and safety of atorvastatin 10 mg versus simvastatin 20 mg and atorvastatin 80 mg versus simvastatin 80 mg was determined in a 6-week, prospective, randomized, open-label, blinded end-point trial of dyslipidemic patients with and without coronary heart disease. A total of 1,732 patients with hypercholesterolemia and triglycerides < or =600 mg/dl (6.8 mmol/L) were randomized to receive either atorvastatin 10 mg (n = 650), simvastatin 20 mg (n = 650), atorvastatin 80 mg (n = 216), or simvastatin 80 mg (n = 216). The primary efficacy parameter was the change in low-density lipoprotein (LDL) cholesterol from baseline to week 6. Secondary efficacy parameters included the percent change from baseline to week 6 in total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, very-low-density lipoprotein cholesterol, apolipoprotein B, and the percent of patients achieving their National Cholesterol Education Program (NCEP) LDL cholesterol goal at study end. Atorvastatin had significantly greater reductions from baseline in LDL cholesterol than simvastatin in both comparator groups: atorvastatin 10 mg (37.1%) versus simvastatin 20 mg (35.4%) (p = 0.0097), and atorvastatin 80 mg (53.4%) versus simvastatin 80 mg (46.7%) (p <0.0001). Atorvastatin 10 and 80 mg also provided significantly greater reductions in total cholesterol, triglycerides, very-low-density lipoprotein cholesterol, and apolipoprotein B than simvastatin 20 and 80 mg, respectively (all p <0.05). All treatment groups had a significantly decreased LDL cholesterol/HDL cholesterol ratio from baseline (all p <0.0001). In both comparator groups a higher proportion of atorvastatin-treated patients reached their NCEP LDL cholesterol goal compared with simvastatin. All 4 study treatments were well tolerated.", "Lipid-lowering therapy was shown to have several beneficial effects in patients with coronary artery disease (CAD).\n The objective of this study was to investigate the effect of atorvastatin on platelet aggregation in patients with CAD.\n Twenty-five hypercholesterolaemic patients who had angiographically proven CAD and 16 normal subjects were enrolled. All patients received 10 mg/day atorvastatin for two months. Anti-platelet agents were discontinued 15 days prior to blood sampling at the beginning and at the end of the atorvastatin therapy. Aggregometric curves of the platelets in response to ADP, collagen and epinephrine were obtained using the aggregometry (turbidimetric) technique.\n In patients with CAD, total cholesterol (TC) and LDL cholesterol (LDL-C) basal levels were measured (230 +/- 49 mg/dl, 140 +/- 41 mg/dl, respectively). Following lipid-lowering therapy, TC and LDL-C decreased significantly (p < 0.05). The activation measurements of aggregometric curves decreased significantly compared with basal parameters in response to ADP but not in response to collagen and epinephrine.\n Lipid-lowering therapy with the HMG-CoA reductase inhibitor, atorvastatin, had a marked reduction effect on platelet aggregation.", "No consensus has been reached on whether the 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have beneficial effects on bone health. The purpose of our study was to evaluate the effects of atorvastatin on bone metabolism by means of measuring bone turnover markers in male patients with hypercholesterolemia both at diagnosis and prospectively after 3 months of treatment. Twenty-two Japanese male patients (mean age 62.36 +/- 10.1 years) with untreated hypercholesterolaemeia were selected for this study. After 3-months treatment of atorvastatin, total cholesterol and low density lipoprotein cholesterol significantly decreased as expected (p<0.001 for both parameters). Bone-specific alkaline phosphatase (BAP) did not change significantly (p = 0.444). However, serum N-terminal telopeptide of type I collagen (NTx) significantly decreased by -19.86 +/- 26.4% (p = 0.020). In addition, delta NTx during the course of this study was negatively correlated with NTx at baseline (r = -0.645, p = 0.0008). Although there was a tendency of positive correlations of delta NTx with delta total cholesterol, delta triglycerides, and delta low density lipoprotein cholesterol, and of negative correlations of delta NTx and delta BAP with delta high density lipoprotein cholesterol, none of them reached statistical significance. Our findings suggest that atorvastatin may have potentially beneficial effects on bone metabolism in patients with hypercholesterolemia mostly by reducing bone resorption rather than by stimulating bone formation. Further studies with more patients and longer duration are warranted to evaluate its effects, if any, on prevention of osteoporosis and subsequent fractures.", "The main effect of statins is the decrease of serum level of low-density lipoprotein (LDL) cholesterol, due to the inhibition of intracellular cholesterol biosynthesis which brings about an upregulation of LDL receptors. A minor effect is the decrease of serum triglycerides. The present study was undertaken to verify whether all statins are effective in reducing serum triglycerides and whether their effect on triglycerides is related to the LDL cholesterol lowering activity.\n Of 197 hypercholesterolaemic patients on stable low-fat low-cholesterol diet, 49 were put on atorvastatin 10 mg per day, 48 on fluvastatin 40 mg per day, 50 on pravastatin 20 mg per day and 50 on simvastatin 10 mg per day.\n After 2 months, mean percentage change in serum triglycerides and LDL cholesterol resulted to be significantly different among the four treatment groups, whereas the ratio between the percentage decrease in serum triglycerides and that of LDL cholesterol (Deltatriglyceride/DeltaLDL cholesterol ratio) was not significantly different. Only baseline serum triglycerides resulted to be significantly associated with Deltatriglycerides/DeltaLDL cholesterol ratio. All statins are then effective in decreasing triglyceride levels.\n The lack of a significant difference in Deltatriglycerides/DeltaLDL cholesterol ratio among the treatment groups suggests that the more effective the statin is in decreasing LDL cholesterol, the more it will also be in decreasing serum triglycerides.", "The use of HMG-CoA-reductase inhibitors (statins) has been associated with decreased risk of bone fractures in epidemiological studies. In vitro evidence suggests that statins may stimulate bone formation, but the data are still preliminary. We assessed the effects of the HMG-CoA-reductase inhibitor atorvastatin on biochemical parameters of bone metabolism in a multicenter, randomized, double-blind, placebo-controlled trial conducted between October 2001 and October 2002 in three hospital-based outpatient metabolism clinics. Forty-nine postmenopausal women, mean age 61 +/- 5 years, mean time postmenopause 12.6 +/- 8.8 years, were treated with atorvastatin, 20 mg per day ( n=24) or matching placebos ( n=25) for 8 weeks. Comparing the differences to baseline between the groups, there were no statistically significant effects of atorvastatin either on the bone formation markers intact osteocalcin and bone-specific alkaline phosphatase or on the bone resorption markers C-telopeptide and intact parathyroid hormone. The marker of bone fractures, undercarboxylated osteocalcin, was also unchanged. When analyzed in dependence of age, atorvastatin increased C-telopeptide and osteocalcin in the younger subjects, while it decreased them in older subjects. Most interestingly, in older subjects, atorvastatin caused a significant decrease in the ratio of C-telopeptide to osteocalcin, an indicator of bone remodeling, while the ratio was increased in younger subjects, suggesting beneficial effects on bone turnover exclusively in older individuals (approx. >63 years). In summary, the present data suggest that short-term treatment with atorvastatin may have age-dependent effects on biochemical markers of bone turnover in postmenopausal women.", "This double-blind, multicenter, randomized trial compared rosuvastatin and atorvastatin for reducing low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia and a high risk of coronary heart disease.\n After a 6-week dietary lead-in period, patients with LDL-C levels > or =160 and <250 mg/dL and triglyceride levels < or =400 mg/dL were randomly assigned to 24 weeks' treatment in 1 of 3 groups, each with forced dose titrations at 12 and 18 weeks. Starting and titrated doses for each group were rosuvastatin 5, 20, and 80 mg (n = 127); rosuvastatin 10, 40, and 80 mg (n = 128); and atorvastatin 10, 40, and 80 mg (n = 128).\n At 24 weeks, LDL-C was reduced significantly more with 80 mg rosuvastatin (combined rosuvastatin group) than with atorvastatin 80 mg (60% vs 52% [P <.001]). At 12 weeks, rosuvastatin 5 and 10 mg reduced LDL-C significantly more than atorvastatin 10 mg (40% [P <.01], 47% [P <.001] vs 35%). At 18 weeks, LDL-C reductions were also significantly greater in both rosuvastatin groups than in the atorvastatin group (52% [P <.01], 59% [P <.001] vs 47%). Consequently, more patients receiving rosuvastatin achieved LDL-C goals. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoproteins B and A-I, and all lipid ratios were more favorably modified by rosuvastatin at 24 weeks (P <.01). Effects of the 2 agents on triglycerides were similar.\n Rosuvastatin was more efficacious than atorvastatin in modifying lipids in patients with hypercholesterolemia and a high coronary heart disease risk.", "Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular mortality by decreasing cholesterol as well as by non-lipid-related actions. Oxidized low-density lipoproteins (ox-LDL) are pro-atherogenic molecules and potent platelet agonists. CD36 and lectin-like ox-LDL receptor-1 (LOX-1) are specific ox-LDL receptors also expressed in platelets. This study was planned to address whether treatment with atorvastatin 10 mg/day, pravastatin 40 mg/day or simvastatin 20 mg/day could affect platelet CD36 and LOX-1 expression. Twenty-four patients for each treatment were evaluated after 3, 6, and 9 days and at 6 weeks for complete lipid profile (chromogenic), ox-LDL (ELISA), platelet P-selectin (P-sel), CD36, LOX-1 (FACS), and intracellular citrullin recovery (iCit) (HPLC). Data show hyperactivated platelets (P-sel absolute values, percent variation in activated cells, all p < 0.001), and CD36 and LOX-1 overexpression (all p < 0.001) in patients at baseline. P-sel, CD36, and LOX-1 were significantly decreased by atorvastatin and simvastatin (all p < 0.01) and related with iCit increase (r = 0.58, p < 0.001) and platelet-associated ox-LDL (r = 0.51, p < 0.01) at 9 days. Pravastatin reduced LOX-1 and P-sel (p < 0.05) at 6 weeks in relation with decreased LDL and ox-LDL (r = 0.39, p < 0.01 and r = 0.37, p < 0.01, respectively). These data suggest that atorvastatin and simvastatin reduce platelet activity by exposure of CD36 and LOX-1 before significant LDL reduction, whereas pravastatin action is detected later and in relation with LDL and ox-LDL lowering. Rapid and consistent reduction of CD36 and LOX-1 could be considered a direct anti-atherothrombotic mechanism related to the role of ox-LDL in platelet activation, platelet-endothelium interactions, and NO synthase activity.", "Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as non-lipid related actions. Among them, the modulation of fibrinolysis could play a relevant role in vascular protection. Atorvastatin is able of reducing platelet activity and thrombin generation before low-density lipoprotein cholesterol (LDL-C) decrease in hypercholesterolemic subjects in which coagulation and fibrinolysis are linked by the activation of thrombin activable fibrinolysis inhibitor (TAFI). The aim of our study was to evaluate whether atorvastatin could modulate fibrinolysis by interactions with endothelial mechanisms and thrombin generation.\n Forty-four pure hypercholesterolemic subjects (26 M, 18 F, mean age 52.7+/-13.7, LDL-C 194.8+/-9.3t mg/dl) were evaluated for plasmin-antiplasmin complexes (PAP), tissue-plasminogen acivator (t-PA) and its inhibitor (PAI-1) (ELISA), TAFI activity (HPLC), platelet P-selectin (P-sel) (cytofluorymetric detection), platelet-dependent thrombin generation (PDTG, coagulative-chromogenic method) and lipid profile at baseline and after 7, 14, 28 and 90 days of atorvastatin (10 mg/die) treatment.\n PAP were significantly reduced at baseline in hypercholesterolemic versus control subjects (P<0.05) and were related to P-sel (P<0.01), PDTG (P<0.01) and its inhibitor (PAI-1) after venous occlusion (VO) (P<0.05). Atorvastatin induced a significant increase of PAP at T(2) related to modifications of P-sel (P<0.01) and PDTG (P<0.01) before significant LDL-C reduction (P=0.132). PAI-1 was significantly changed at T(3) with relation to LDL-C (P<0.01), Von Willebrand factor (VWF) (P<0.01) and sE-sel (P<0.05).\n The profibrinolytic activity of atorvastatin in hypercholesterolemic subjects is related, initially, to the positive effects exerted on platelet function and thrombin generation which can modulate fibrinolysis by TAFI activity.", "Platelets and monocytes are involved in atherothrombosis via tissue factor expression. Moreover, they are activated in hypercholesterolemia, a classic risk factor for atherothrombosis. Cholesterol-lowering drugs (statins) reduce cardiovascular risk either by decreasing cholesterol or non-lipidic actions, such as platelet and monocyte activity. The aim of our study was to evaluate the effect of several statins on platelet and monocyte activity in hypercholesterolemic subjects. Platelet activity (P-selectin, cytofluorimetric detection), tissue factor levels (ELISA) and activity (detected in whole blood and cellular preparations by a specific clotting assay) were measured in hypercholesterolemic subjects (41 males, 23 females, aged 34-65 years, total cholesterol 6.86+/-0.60 mmol/l) treated with atorvastatin 10 mg, simvastatin 20 mg, fluvastatin 40 mg, or pravastatin 40 mg for 6 weeks. P-selectin and tissue factor expression in whole blood and isolated cells were increased in hypercholesterolemic subjects with respect to controls (all P<0.001). Simvastatin, atorvastatin, and fluvastatin reduced monocyte procoagulant activity in whole blood and P-selectin (P<0.01). Tissue factor antigen and activity in isolated cells were further reduced (all P<0.05) independently of cholesterol lowering. Pravastatin decreased tissue factor expression in whole blood in direct relationship to reduction of P-sel and cholesterol (P<0.05). Our data show a different impact of several statins on monocyte tissue factor expression in whole blood, suggesting a possible role of decreased platelet activity and a direct action on monocytes. In contrast, pravastatin decreased monocyte procoagulant activity with relation to cholesteroldependent modifications of platelet function.", "Vaspin and visfatin have emerged as novel adipokines, involved in atherosclerosis progression. The aim of the present study was to investigate the effects of atorvastatin and lifestyle modification on the above adipokines in hypercholesterolemic patients.\n One hundred four statin-free subjects with moderate cardiovascular risk (Framingham risk score of 10-20%) were randomly assigned to receive either atorvastatin 20mg per day (AT group, n=52) or lifestyle modification (LM, group, n=52). For comparison, age and gender-matched blood donors, without any chronic cardiovascular or metabolic disease served as healthy controls (HC group, n=40). Clinical and anthropometrical parameters, lipids, fasting glucose, serum vaspin, visfatin and insulin levels were obtained at the beginning and after 12 weeks.\n At the end of the study, intra-group and inter-group comparison revealed that atorvastatin administration considerably ameliorated most lipid parameters and downregulated hsCRP levels (p=0.002, p=0.041, respectively). Moreover, we observed a significant increase of vaspin concentrations after 12-week atorvastatin treatment (from 1.37±0.6ng/ml to 2.13±0.61ng/ml), as compared to baseline (p=0.007) and LM group (p=0.030). In standard multiple regression analysis, the atorvastatin-induced decrease of vaspin was independently associated with hsCRP reduction (p=0.015). On the other hand, within and between groups comparison revealed a non-significant (p>0.05) reduction of visfatin serum levels. In our study, lifestyle modification had totally modest influence on clinical and biochemical variables (p>0.05).\n In hypercholesterolemic patients with moderate estimated cardiovascular risk, atorvastatin administration reduced hsCRP and increased serum vaspin levels compared to lifestyle modification. The relation of those pleiotropic, non-lipid-lowering effects of statins with their clinical outcomes remains to be proved.\n Copyright © 2011 Elsevier B.V. All rights reserved.", "Epidemiologic studies have shown that serum uric acid is a risk factor of coronary artery disease. In addition to fenofibrate, there is some evidence that atorvastatin may have a hypouricemic action, but the underlying mechanisms remain speculative.\n This randomized trial was conducted to investigate the effects of atorvastatin and simvastatin on uric acid homeostasis in patients treated for primary hyperlipidemia. A total of 180 patients were enrolled; patients were randomly assigned to 40 mg/d of either atorvastatin or simvastatin. Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment; random urine samples were simultaneously obtained for creatinine, sodium, and uric acid determinations.\n Baseline serum uric acid levels correlated positively with the body mass index, serum insulin, creatinine, and triglyceride levels and inversely with serum HDL cholesterol levels. Both statins caused a favorable effect on lipids and a significant decrease in fibrinogen and high-sensitivity CRP levels. However, only atorvastatin reduced serum uric acid levels (from 5.6 +/- 1.7 to 4.9 +/- 1.5 mg/dL, P <.0001) by augmenting its urinary fractional excretion (from 10.4% +/- 7.9% to 12.0% +/- 7.4%, P <.01). In a multivariate logistic regression analysis, the reduction of uric acid levels was independently associated with baseline serum uric acid concentration but not to other variables, including lipid parameters (OR, 1.65; 95% CI, 1.14 to 2.40; P =.008).\n Atorvastatin (but not simvastatin) significantly lowered serum uric acid levels. This result may be in favor of a preferable choice of atorvastatin for the treatment of hyperlipidemic patients presenting with hyperuricemia.", "The purpose of this study was to examine the effects of statin therapy on lipoprotein particle concentrations in patients with the metabolic syndrome. Changes in lipoprotein particle concentration may predict the risk of coronary heart disease more accurately than lipoprotein cholesterol levels.\n Patients with dyslipidemia and the metabolic syndrome (n = 318) were randomly assigned in a double-blind study comparing 10 mg rosuvastatin (RSV), 10 mg atorvastatin, or placebo daily for 6 weeks. From weeks 6 to 12, patients in the RSV and placebo groups received 20 mg RSV, whereas the ATV group increased their dose to 20 mg daily. Lipoprotein particle concentrations were measured by nuclear magnetic resonance spectroscopy, LDL cholesterol was measured by beta-quantification, and other lipoproteins were measured by standard methods at baseline, 6 weeks, and 12 weeks. Lipoprotein levels were compared by analysis of covariance.\n Statins reduced LDL particle concentration less than LDL cholesterol (-30 to -38 vs. -38 to -51%). Reductions were greater with RSV than with ATV (P < 0.05 for LDL particle concentration and P < 0.001 for LDL cholesterol). Most patients attained LDL cholesterol <2.59 mmol/l (100 mg/dl) at 12 weeks (80% with RSV and 59% with ATV; P = 0.003), but only 27% of patients receiving RSV and 19% receiving ATV attained the goal of LDL particle concentration <1,000 nmol/l (P = 0.07).\n In patients with the metabolic syndrome, statin-induced changes in LDL cholesterol do not accurately reflect changes in LDL particle concentration. Consequently, despite attainment of LDL cholesterol goals, these patients may retain considerable residual coronary heart disease risk.", "The object of our study was to compare the effect of high-dose vs low-dose atorvastatin vs nonstatin-based treatment (cholestyramine plus sitosterol) on cell composition of carotid plaque.\n We recruited 60 hypercholesterolemic patients (total cholesterol, 5.83-7.64 mmol/L) eligible for carotid endarterectomy. Three months before surgery, patients were randomized into 3 groups (n=20) receiving atorvastatin 10 mg/day (AT-10) or atorvastatin 80 mg/day (AT-80) or cholestyramine 8 g/day plus sitosterol 2.5 g/day. Analysis of cell composition was performed on endarterectomy specimens.\n The 3 treatments resulted in a significant reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), although the decrease in total cholesterol and LDL-C was of smaller magnitude in the cholestyramine plus sitosterol group. The 3 regimens did not influence the levels of inflammatory markers (including high-sensitivity C-reactive protein). Macrophage content was significantly lower in the AT-10 group plaques compared to the cholestyramine plus sitosterol group. It was further reduced in the AT-80 group plaques. These differences were no longer significant after adjustment for changes in LDL-C. No difference in lymphocyte number was observed among treatments, whereas the content of smooth muscle cells was higher in the AT- 80 group. An inverse association was observed between LDL-C changes in the 3 groups and macrophage content in the plaques.\n Short-term treatment with high-dose statin is superior to a nonstatin lipid-lowering regimen in reducing the macrophage cell content within atherosclerotic lesions, but this effect was determined by the degree of LDL-C-lowering.", "To compare the efficacy and safety of pitavastatin and atorvastatin in Japanese patients with hypercholesterolemia.\n Japanese patients with total cholesterol (TC) > or = 220 mg/dL were randomized to receive pitavastatin 2 mg (n=126) or atorvastatin 10 mg (n=125) for 12 weeks. The primary endpoint was percent change from baseline in non-HDL-C level after 12 weeks of treatment. Reduction of non-HDL-C by pitavastatin treatment (39.0%, P=0.456 vs. atorvastatin) was non-inferior to that by atorvastatin (40.3%). Both pitavastatin and atorvastatin also significantly reduced LDL-C by 42.6% and 44.1%, TC by 29.7% and 31.1%, and TG by 17.3% and 10.7%, respectively, at 12 weeks without intergroup differences. HDL-C showed a significant increase at 12 weeks with pitavastatin treatment (3.2%, P=0.033 vs. baseline) but not with atorvastatin treatment (1.7%, P=0.221 vs. baseline). Waist circumference, body weight and BMI were significantly correlated with percent reduction of non-HDL-C in the atorvastatin group, whereas pitavastatin showed consistent reduction of non-HDL-C regardless of the body size. In patients with metabolic syndrome, LDL-C was reduced significantly more in patients receiving pitavastatin when compared with those receiving atorvastatin. AST, ALT and gammaGTP increased significantly in patients receiving atorvastatin but not in those receiving pitavastatin. Both treatments were well tolerated.\n Pitavastatin 2 mg and atorvastatin 10 mg are equally effective in improving the lipid profile and were well tolerated in Japanese patients with hypercholesterolemia.", "The effects of atorvastatin, a new synthetic HMG-CoA reductase inhibitor, were investigated in patients with familial hypercholesterolaemia (FH), with high LDLc levels whilst on standard treatment.\n Open treatment with 40 mg atorvastatin daily for 6 weeks, followed by another 6 weeks with 80 mg atorvastatin.\n Outpatient lipid clinic of a tertiary referral centre.\n FH was diagnosed when the untreated LDLc concentration was higher than 6 mmol L-1, tendon xanthomas were present at the participant or a first degree relative, and the family history for hypercholesterolaemia was positive. The FH patients were selected for an LDLc above 5.0 mmol L-1 whilst on standard therapy for at least 3 months. Standard therapy consisted of a diet and 40 mg simvastatin, either alone (n = 17), or in combination with 8-12 g colestyramin (n = 12), or 1800 mg nicotinic acid (n = 12).\n Effects on LDLc concentration.\n LDLc concentration significantly decreased during treatment with 80 mg atorvastatin as compared to LDLc levels on 40 mg simvastatin alone or in combination with 8-12 g colestyramin, by 24 +/- 14% (P < 0.01) and 19 +/- 22% (P < 0.01), respectively. LDLc concentration was comparable during treatment with 80 mg atorvastatin or 40 mg simvastatin in combination with 1800 mg nicotinic acid. Atorvastatin was tolerated well, no side-effects were observed.\n Atorvastatin is a valuable addition to the treatment possibilities of patients with serious hypercholesterolaemia, like FH.", "Uncontrolled studies have shown that statins can improve cerebral vasoreactivity (CVR) in patients with mild small vessel disease. We sought to determine whether high-dose atorvastatin increases CVR compared with placebo in patients with severe small vessel disease.\n Ninety-four adults with recent lacunar stroke were randomly allocated in a double-blind manner to 80 mg of atorvastatin daily or matching placebo after stratification for hypertensive and diabetic status. The primary end point was change in CVR after 3 months of treatment. Secondary outcomes were changes in brachial and carotid artery endothelial-dependent vasodilations.\n At baseline, all patients had a severely impaired CVR (mean, 12.1%; 95% CI, 9.5-14.7) and carotid (mean, -0.25%; 95% CI, -1.17-0.67) and brachial artery (mean, 2.72%; 95% CI, 1.39-4.05) endothelial function. Despite reductions of 55% in low-density lipoprotein cholesterol and of 30% in high-sensitivity C-reactive protein in the active arm compared to placebo, atorvastatin 80 mg per day did not improve CVR or endothelial dysfunction of carotid and brachial arteries.\n We found no positive effect of 3-month treatment with atorvastatin on severe cerebral microvasculature endothelial dysfunction in patients with lacunar stroke.", "In a large randomized trial of statin therapy in patients of South-Asian origin with hypercholesterolemia, 740 patients in the United States and Canada received 6 weeks of treatment with rosuvastatin 10 or 20 mg or atorvastatin 10 or 20 mg. A total of 485 patients (66%) were categorized as being at high risk of coronary heart disease and had a National Cholesterol Education Program Adult Treatment Panel III treatment goal of low-density lipoprotein (LDL) cholesterol <100 mg/dl (<2.6 mmol/L). LDL cholesterol decreased by 45% with rosuvastatin 10 mg versus 40% with atorvastatin 10 mg (p = 0.0023) and by 50% with rosuvastatin 20 mg versus 47% with atorvastatin 20 mg (p = NS). National Cholesterol Education Program Adult Treatment Panel III LDL cholesterol goal achievement rates in high-risk patients (all patients) were 76% (79%) and 88% (89%) with rosuvastatin 10 and 20 mg, respectively, compared with 70% (76%) and 81% (85%) with atorvastatin 10 and 20 mg, respectively. Rosuvastatin and atorvastatin were well tolerated. There were no clinically relevant differences between statins in adverse events or incidence of creatine kinase >10 times the upper limit of normal, alanine aminotransferase >3 times the upper limit of normal on 2 consecutive occasions, or proteinuria or hematuria over the relatively short duration of treatment. In conclusion, statin therapy was well tolerated and effective in decreasing LDL cholesterol in patients of South-Asian origin, with the 10- and 20-mg doses of rosuvastatin and atorvastatin allowing most patients to reach recommended LDL cholesterol goals.", "Therapeutic strategies to raise low plasma HDL-cholesterol levels, with concomitant normalization of the intravascular metabolism, physicochemical properties, and antiatherogenic function of HDL particles, are a major focus in atherosclerosis prevention.\n Patients displaying Type IIB hyperlipidemia (n=14) and healthy controls (n=11) were recruited. After drug washout, dyslipidemic patients first received atorvastatin (10 mg/d) for 6 weeks and subsequently torcetrapib/atorvastatin (60/10 mg/d) for the same period. Partial CETP inhibition markedly reduced supranormal CE transfer rates to normal levels from HDL3 (-58%; P<0.0001) to apoB-lipoproteins; endogenous CE transfer rates from HDL2 to apoB-lipoproteins were markedly subnormal as compared to those in control subjects (10.7+/-0.9 versus 29.3+/-4.8 microg CE/h/mL plasma, respectively). Torcetrapib enhanced the subnormal capacity of HDL2 particles from dyslipidemic patients to mediate free cholesterol efflux via both SR-BI and ABCG1 pathways (+38%; P<0.003 and +35%; P<0.03, respectively) as compared to baseline. In vitro observations and in vivo studies in mice demonstrated that CETP inhibition was associated with an enhanced selective hepatic uptake of CE from HDL particles (1.7-fold; P<0.0003).\n CETP inhibition partially corrected the abnormal physicochemical and functional properties of HDL2 and HDL3 particles in type IIB hyperlipidemia. Enhanced hepatic selective uptake of HDL-CE may compensate for attenuated indirect CE transfer to apoB-containing lipoproteins via CETP attributable to torcetrapib.", "It has been suggested that lipid-lowering treatment with the use of statins adversely affects the steroid hormones. However, the safety of lipid lowering treatment targeting very low levels of LDL with respect to the steroid hormones has not been established.\n A prospective, randomized, multicenter trial was conducted involving 98 patients. The patients were randomized into 2 groups: group-I received 10 mg of atorvastatin plus 10 mg of ezetimibe and group-II 80 mg of atorvastatin for the first 3 months. After crossover, the first group received 80 mg of atorvastatin and the second group 10 mg of atorvastatin plus 10 mg of ezetimibe for the following 3 months. Cortisol, DHEAS, testosterone, and estradiol levels were measured at the enrollment and at the end of the 1st, 2nd, 3rd, and 6th months.\n Along with a decrease in LDL level, the levels of DHEAS, testosterone, and estradiol decreased in both groups (p<0.001). While cortisol levels were maintained in the group given 10 mg of atorvastatin plus 10 mg of ezetimibe, it decreased significantly after the crossover to 80 mg of atorvastatin (p<0.001). The group initially given 80 mg of atorvastatin measured a lower level of cortisol for the first 3 months and it returned to normal levels after switching to 10 mg of atorvastatin plus 10 mg of ezetimibe.\n Eighty milligrams of atorvastatin decreased all adrenal and gonadal steroids, whereas 10 mg of ezetimibe combined with 10 mg of atorvastatin had at least no impact on cortisol levels.", "Little is known about the impact of gender on short-term effects of atorvastatin. We investigated the gender differences in the short-term lipid-lowering and pleiotropic effects of atorvastatin therapy.\n Seventy-two consecutive patients including 48 women with primary hypercholesterolemia, were assigned prospectively to treatment with atorvastatin (10mg/day) for 3 months. We measured fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS) as marker of lipid peroxide, fibrinolytic parameters, and endothelial function by flow-mediated vasodilation of the brachial artery (FMD), at baseline and after 3 months of therapy. We assessed the impact of gender on temporal differences in these parameters. In men, atorvastatin decreased total, low-density lipoprotein (LDL), and small, dense LDL-cholesterol concentrations, and increased FMD after 3 months. In women, atorvastatin decreased TBARS, triglyceride, and total, LDL, small, dense LDL, and remnant-like lipoprotein particle-cholesterol concentrations, and increased FMD after 3 months. Fibrinolytic parameters did not change significantly in either men or women. With respect to the percent change in those parameters after 3 months, TBARS (-17.6+/-12.4 vs. -0.4+/-18.8%, p<0.01) and small, dense LDL-cholesterol (-96.7+/-8.3 vs. -68.6+/-29.7%, p<0.01) decreased to a greater degree in women, although the relative changes in other parameters were similar between men and women.\n We found gender differences in some of the lipid altering changes, including TBARS and small, dense LDL-cholesterol concentrations, after short-term atorvastatin therapy, which were greater in women. However, short-term atorvastatin therapy may be beneficial in improving endothelial function equally in both men and women.", "Rosuvastatin is a new, synthetic, orally active statin, with marked low-density lipoprotein (LDL) cholesterol-lowering activity. We conducted 2 dose-ranging studies. In the first study, after a 6-week dietary run-in, 142 moderately hypercholesterolemic patients were randomized equally to receive double-blind placebo or rosuvastatin 1, 2.5, 5, 10, 20, or 40 mg or open-label atorvastatin 10 or 80 mg once daily for 6 weeks; in the second study, conducted to extend the rosuvastatin dose range, 64 patients were randomized to double-blind, once-daily placebo or rosuvastatin 40 or 80 mg (1:1:2 ratio) for 6 weeks. Data from both studies were combined for analysis of lipid effects. No statistical comparison of atorvastatin arms with placebo or rosuvastatin was performed. Rosuvastatin was associated with highly significant dose-dependent reductions in LDL cholesterol compared with placebo (p <0.001); decreases ranged from 34% (1 mg) to 65% (80 mg). Linear regression analysis indicated an additional 4.5% LDL cholesterol reduction for each doubling of the rosuvastatin dose. Across the dose range, approximately 90% of LDL cholesterol reduction occurred within the first 2 weeks of treatment. Significant, dose-dependent reductions in total cholesterol and apolipoprotein B with rosuvastatin were also observed (p <0.001). High-density lipoprotein cholesterol increases and triglyceride reductions were consistently observed and statistically significant at some dose levels. All lipid ratios were significantly reduced at all rosuvastatin dose levels (p <0.001). Adverse events were similar across placebo and active treatments. No significant increases in alanine aminotransferase or creatine kinase were seen in any patient. Over 6 weeks, rosuvastatin produced large, rapid, dose-dependent LDL cholesterol reductions and was well tolerated in hypercholesterolemic patients.", "Information about lipid abnormalities and the effect of lipid lowering therapy in the early stage of renal disease is limited, while preventive treatment in this stage might be much more beneficial. Lipid profiles and risk factors were assessed in 150 consecutive, non-diabetic patients. Preventive therapy consisted of cholesterol-reduced diet and atorvastatin 10 mg daily. Patients were considered at risk for cardiovascular disease if LDL-cholesterol was >2.6 mmol/l in the case of manifest cardiovascular disease (n=28) or when they had manifest cardiovascular risk factors (n=105) or if LDL was >3.5 mmol/l (n=17). A total of 128 patients (85%) had increased LDL. In men <60 years and women <40 years, total cholesterol was higher than in the general population. Linear regression analysis showed a decreased creatinine clearance to be significantly associated with the lipid profile. For a 10 ml/min decrease of creatinine clearance, a 0.085 increase of the total cholesterol to HDL ratio was observed (P=0.005). In similar analyses, proteinuria was strongly associated with cholesterol and triglycerides. An increase of 0.28 of the total cholesterol/HDL ratio was observed for each gram per 24 h proteinuria (P<0.001). On atorvastatin 10 mg daily, 30 of 60 treated patients had achieved their target LDL value. On average, LDL-cholesterol was reduced by 39% and triglycerides by 18%. No patient had to interrupt their treatment because of adverse side-effects. In conclusion, the majority of patients had an elevated LDL and other lipid abnormalities. Short-term therapy with atorvastatin and a cholesterol lowering diet appears to be safe and effective. It is probably useful to determine the lipid profile in patients with renal failure already in an early phase and to start lipid lowering treatment as soon as abnormalities are found.", "To explore the effect of short-term cholesterol-lowering treatment with atorvastatin on erythrocyte sodium-lithium countertransport (Na(+)/Li(+) CT) activity.\n Group A consisted of 30 patients (14 men) with mild essential hypertension (systolic blood pressure (SBP), 140-159 mm Hg and/or diastolic BP, 90-99 mm Hg) and primary hypercholesterolemia low-density lipoprotein (LDL) cholesterol >4.1 mmol/l and triglycerides (TG) <2.8 mmol/l), group B of 30 normotensive patients (16 men) with primary hypercholesterolemia, while 37 (18 men) healthy volunteers comprised the control group. After a 6-week dietary lead-in, all eligible patients were prescribed 20 mg/day of atorvastatin. Anthropometric data, blood-pressure (BP) measurements and determinations of lipid, non-lipid metabolic parameters (including homeostasis model assessment index, (HOMA-IR)) and erythrocyte Na(+)/Li(+) CT activity were collected at baseline and after 12 weeks of treatment.\n At baseline Na(+)/Li(+) CT activity was significantly higher in group A and B compared with the control group and correlated directly with obesity indices, systolic and diastolic BP, total cholesterol, LDL-cholesterol, TG, apolipoprotein B (apoB), HOMA-IR, uric acid and inversely with high-density lipoprotein (HDL)-cholesterol and apoA1. Systolic and diastolic BP levels, HOMA-IR and Na(+)/Li(+) CT activity were significantly decreased after atorvastatin treatment in both patient groups. The reduction in Na(+)/Li(+) CT activity correlated with baseline Na(+)/Li(+) CT activity and the changes in HOMA-IR values.\n Short-term treatment with atorvastatin for patients with hypercholesterolemia, and with or without essential hypertension, is associated with a significant reduction in the erythrocyte Na(+)/Li(+) CT activity, BP levels and insulin resistance independent of concomitant changes in lipid parameters.", "Type 2 diabetes mellitus is associated with elevated plasma triglyceride levels, low high-density lipoprotein cholesterol, and a high incidence of cardiovascular disease. Hydroxymethylglutaryl-coenzyme A reductase inhibitors and fibrates are frequently used in the treatment of diabetic dyslipidemia, but their specific impact on the inflammation processes involved in atherosclerosis remains to be fully characterized. The objective of this 2-group parallel study was to investigate the differential effects of a 6-week treatment with either atorvastatin 20 mg/d alone (n = 19) or micronized fenofibrate 200 mg/d alone (n = 19) on inflammation, cell adhesion, and oxidation markers in type 2 diabetes mellitus subjects with marked hypertriglyceridemia. In addition to the expected changes in lipid levels, atorvastatin decreased plasma levels of C-reactive protein (-26.9%, P = .004), soluble intercellular adhesion molecule 1 (-5.4%, P = .03), soluble vascular cell adhesion molecule 1 (-4.4%, P = .008), sE-selectin (-5.7%, P = .02), matrix metalloproteinase 9 (-39.6%, P = .04), secretory phospholipase A(2) (sPLA(2)) (-14.8%, P = .04), and oxidized low-density lipoprotein (-38.4%, P < .0001). On the other hand, fenofibrate had no significant effect on C-reactive protein levels and was associated with reduced plasma levels of sE-selectin only (-6.0%, P = .04) and increased plasma levels of sPLA(2) (+22.5%, P = .004). These results suggest that atorvastatin was potent to reduce inflammation, oxidation, and monocyte adhesion in type 2 diabetes mellitus subjects with marked hypertriglyceridemia, whereas fenofibrate decreased sE-selectin levels only and was associated with an elevation of sPLA(2) levels.", "Diabetic dyslipidemia is featured by hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol levels, and elevated low-density lipoprotein (LDL) cholesterol commonly in the form of small, dense LDL particles. First-line treatment, fibrates versus statins or both, of dyslipidemia in diabetic patients has been the focus of debate. We investigated the potential hypolipidemic effects of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor with good triglyceride lowering properties, in patients with combined dyslipidemia and evidence of impaired fasting glucose or type 2 diabetes. Twenty patients were recruited for the study, and after a 60-day wash out period, baseline measurements of lipoprotein parameters, LDL particle diameter, and apolipoprotein B (apoB) degradation fragments were obtained. The group was then randomized, in a double-blinded manner, into 2 subgroups. Group A received atorvastatin (80 mg) and group B received placebo daily for 60 days. After the first treatment period, all patients were reanalyzed for the above parameters. The treatment regime then crossed over for the second treatment period in which group A received placebo and group B received atorvastatin (80 mg) daily for 60 days. All parameters were remeasured at the end of the study. Treatment with atorvastatin resulted in a statistically significant reduction in total cholesterol (41%), LDL cholesterol (55%), triglycerides (TG) (32%), and apoB (40%). Mean LDL particle diameter significantly increased from 25.29 +/- 0.24 nm (small, dense LDL subclass) to 26.51 < 0.18 nm (intermediate LDL subclass) after treatment with atorvastatin (n = 20, P <.005). At baseline, LDL particles were predominantly found in the small, dense subclass; atorvastatin treatment resulted in a shift in the profile to the larger and more buoyant LDL subclass. Atorvastatin treatment did not produce consistent changes in the appearance of apoB degradation fragments in plasma. Our results suggest that atorvastatin beneficially alters the atherogenic lipid profile in these patients and significantly decreases the density of LDL particles produced resulting in a shift from small, dense LDL to more buoyant and less atherogenic particles.\n Copyright 2002 by W.B. Saunders Company", "The specific impact of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors and fibrates on the in vivo metabolism of apolipoprotein (apo) B has not been systematically investigated in patients with type 2 diabetes mellitus with high plasma triglyceride (TG) levels. Therefore, the objective of this 2-group parallel study was to examine the differential effects of a 6-week treatment with atorvastatin or fenofibrate on in vivo kinetics of apo B-48 and B-100 in men with type 2 diabetes mellitus with marked hypertriglyceridemia. Apolipoprotein B kinetics were assessed at baseline and at the end of the intervention using a primed constant infusion of [5,5,5-D(3)]-l-leucine for 12 hours in the fed state. Fenofibrate significantly decreased plasma TG levels with no significant change in plasma low-density lipoprotein cholesterol (LDL-C) and apo B levels. On the other hand, atorvastatin significantly reduced plasma levels of TG, LDL-C, and apo B. After treatment with fenofibrate, very low-density lipoprotein (VLDL) apo B-100 pool size (PS) was decreased because of an increase in the fractional catabolic rate (FCR) of VLDL apo B-100. No significant change was observed in the kinetics of LDL apo B-100. Moreover, fenofibrate significantly decreased TG-rich lipoprotein (TRL) apo B-48 PS because of a significant increase in TRL apo B-48 FCR. After treatment with atorvastatin, VLDL and IDL apo B-100 PSs were significantly decreased because of significant elevations in the FCR of these subfractions. Low-density lipoprotein apo B-100 PS was significantly lowered because of a tendency toward decreased LDL apo B-100 production rate (PR). Finally, atorvastatin reduced TRL apo B-48 PS because of a significant decrease in the PR of this subfraction. These results indicate that fenofibrate increases TRL apo B-48 as well as VLDL apo B-100 clearance in men with type 2 diabetes mellitus with marked hypertriglyceridemia, whereas atorvastatin increases both VLDL and IDL apo B-100 clearance and decreases TRL apo B-48 and LDL apo B-100 PR.", "The 6-week efficacy and safety of atorvastatin versus simvastatin was determined during a 54-week, open-label, multicenter, parallel-arm, treat-to-target study. In all, 1,424 patients with mixed dyslipidemia (triglyceride 200 to 600 mg/dl [2.26 to 6.77 mmol/L]) were stratified to 1 of 2 groups (diabetes or no diabetes). Patients were then randomized to receive either atorvastatin 10 mg/ day (n = 730) or simvastatin 10 mg/day (n = 694). Efficacy was determined by measuring changes from baseline in lipid parameters including low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and apolipoprotein B. Compared with simvastatin, atorvastatin produced significantly greater (p < 0.0001) reductions from baseline in LDL cholesterol (37.2% vs 29.6%), total cholesterol (27.6% vs 21.5%), triglycerides (22.1% vs 16.0%), the ratio of LDL cholesterol to high-density lipoprotein (HDL) cholesterol (41.1% vs 33.7%), and apolipoprotein B (28.3% vs 21.2%), and a comparable increase from baseline in HDL cholesterol (7.4% vs 6.9%). Atorvastatin was also significantly (p < 0.0001) more effective than simvastatin at treating the overall patient population to LDL cholesterol goals (55.6% vs 38.4%). Fewer than 6% of patients in either treatment group experienced drug-attributable adverse events, which were mostly mild to moderate in nature. Diabetic patients treated with either statin had safety characteristics similar to nondiabetics, with atorvastatin exhibiting superior efficacy to simvastatin. In conclusion, atorvastatin, at a dose of 10 mg/day, is more effective than simvastatin 10 mg/day at lowering lipids and reaching LDL cholesterol goals in patients with mixed dyslipidemia. Both statins are well tolerated with safety profiles similar to other members of the statin class.", "This multicenter, open-labeled, randomized trial was performed to compare the effects of rosuvastatin 10 mg and atorvastatin 10 mg on lipid and glycemic control in Korean patients with nondiabetic metabolic syndrome.\n In total, 351 patients who met the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria for metabolic syndrome with low-density lipoprotein cholesterol (LDL-C) levels > or = 130 mg/dL were randomized to receive either rosuvastatin 10 mg (n = 173) or atorvastatin 10 mg (n = 178) for over 6 weeks.\n After 6 weeks of treatment, greater reductions in total cholesterol (- 35.94 +/- 11.38 vs. - 30.07 +/- 10.46%, p < 0.001), LDL-C (48.04 +/- 14.45 vs. 39.52 +/- 14.42%, p < 0.001), non-high-density lipoprotein cholesterol (- 42.93 +/- 13.15 vs. - 35.52 +/- 11.76%, p < 0.001), and apolipoprotein-B (- 38.7 +/- 18.85 vs. - 32.57 +/- 17.56%, p = 0.002) levels were observed in the rosuvastatin group as compared to the atorvastatin group. Overall, the percentage of patients attaining the NCEP ATP III goal was higher with rosuvastatin as compared to atorvastatin (87.64 vs. 69.88%, p < 0.001). Changes in glucose and insulin levels, and homeostasis model assessment of insulin resistance index were not significantly different between the two groups. The safety and tolerability of the two agents were similar.\n Rosuvastatin 10 mg was more effective than atorvastatin 10 mg in achieving NCEP ATP III LDL-C goals in patients with nondiabetic metabolic syndrome, especially in those with lower NCEP ATP III target level goals.", "A double-blind, placebo-controlled, parallel-group study was performed to determine whether atorvastatin, a new HMG-CoA reductase inhibitor, could effectively and safely reduce plasma LDL-cholesterol concentrations in Japanese patients with type-2 diabetes without influencing glycemic control. The subjects were patients with hypercholesterolemia (serum cholesterol concentration > or =5.7 mmol/l (220 mg/dl)) and stable glycemic control. The fasting concentrations of hemoglobin A(1C) (HbA(1C)), fructosamine, and 1,5-anhydroglucitol (1,5-AG) were measured as indices of glycemic control. Plasma lipid concentrations and the safety of the drug were also examined. Forty eligible patients in two groups of 20 each were administered atorvastatin (10 mg/day) or placebo. Neither atorvastatin nor placebo caused a significant change in HbA(1C), fructosamine, or 1,5-AG concentrations. Atorvastatin significantly reduced total cholesterol and LDL-cholesterol concentrations from baseline by 29.7% (p<0.0001) and 41.6% (p<0.0001), respectively. The incidence of clinical adverse events and that of abnormal changes in laboratory test values did not differ between the two groups. In this trial, atorvastatin effectively and safely reduced LDL-cholesterol concentrations in diabetic patients with hypercholesterolemia without influencing glycemic control. These findings are clinically important because there are many diabetic patients with hypercholesterolemia and such patients have a high risk of developing arteriosclerotic disease.", "Guidelines for the prevention of coronary heart disease call for low-density lipoprotein cholesterol (LDL-C) reduction as the primary target of treatment and reduction of triglycerides (TG) as an additional target.\n The purpose of this study was to investigate the ability of atorvastatin and simvastatin to reduce LDL-C and TG concentrations and to meet 3 target lipid levels: LDL-C <or=2.6 mmol/L; TG <or=1.5 mmol/L; and both LDL-C <or=2.6 mmol/L and TG <or=1.5 mmol/L.\n The Treat-to-Target (3T) Study was a 52-week, multicenter, randomized, parallel-group study. Using the double-blind, double-dummy technique, adult patients aged 35 to 75 years with cardiovascular disease and dyslipidemia, defined as LDL-C concentration >or=4.0 mmol/L (>or=155 mg/dL), were randomized in a 1:1 ratio to receive once-daily oral treatment with 20 mg atorvastatin or 20 mg simvastatin. Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National Cholesterol Education Program level of LDL-C (<or=2.6 mmol/L [100 mg/dL]) was not reached at 8 weeks.\n The intent-to-treat analysis included 552 patients (418 men, 134 women) randomized to receive atorvastatin and 535 (404 men, 131 women) randomized to receive simvastatin. The number of patients enrolled in the study allowed the evaluation fo the drugs' effects on TG. Patient demogrpahic characteristics were similar for the 2 treatment groups, and there were no differences in baseline lipid values. Compared with simvastatin, atorvastatin produced significantly greater reductions in LDL-C (8 weeks: -46% vs -40%, P < 0.001; 52 weeks: -49% vs -44%, P < 0.001) and in TG (8 weeks: -23% vs -14%, P < 0.001; 52 weeks: -24% vs -16%, P < 0.001). Compared with simvastatin-treated patients, a significantly greater number of atorvastatin-treated patients reached the LDL-C target after 8 weeks (45% vs 24%; P < 0.001). Fewer atorvastatin patients needed to have their dose doubled; nevertheless more atorvastatin patients reached the LDL-C target after 52 weeks (61% vs 41%; P < 0.001). Both statins were well tolerated. Muscular symptoms occurred in 12 patients (2.2%) in the atorvastatin group and in 13 patients (2.4%) in the simvastatin group.\n Atorvastatin 20 or 40 mg/d for up to 1 year of treatment was significantly more effective than simvastatin 20 or 40 mg/d in reducing LDL-C and TG levels and at achieving recommended lipid targets in this selected patient population with cardiovascular disease and dyslipidemia. Both statis were well tolerated.", "Simvastatin 40 to 80 mg/d has been found to increase high-density lipoprotein cholesterol (HDL-C) levels significantly more than atorvastatin at equipotent doses (ie, 20-80 mg/d). Data on the effects of lower doses of the 2 drugs on HDL-C levels are conflicting.\n The purpose of this study was to investigate the effects of simvastatin 20 mg/d and atorvastatin 10 mg/d on HDL-C levels in patients with hypercholesterolemia.\n Patients with primary hypercholesterolemia (total cholesterol [TC] >250 mg/dL) who were not taking any lipid-lowering agents and who were following a low-fat diet were randomized to receive 1 of 2 treatments: simvastatin 20 mg/d or atorvastatin 10 mg/d. Serum TC, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and HDL-C levels were measured using standard methods after 2 months of therapy. In a secondary analysis, lipids and lipoprotein cholesterol were measured after 1 year in patients who continued treatment.\n Of the 240 patients enrolled (108 men and 132 women; age range, 23-77 years, mean [SEM] 56.7 [0.69]), 235 completed the study. After 2 months of therapy, TC, LDL-C, and serum TG levels decreased significantly versus baseline in both groups (P < 0.001), with no significant differences between treatment groups. HDL-C levels increased by 9.0% (P < 0.001 vs baseline) in the simvastatin group and by 4.3% (P < 0.02) in the atorvastatin group. The difference between the 2 groups in the percentage increase in HDL-C was statistically significant (P < 0.05). In 113 patients who continued treatment, HDL-C levels at 1 year were still significantly higher than baseline levels in the simvastatin group (6.3%, P = 0.034), but not in the atorvastatin group (2.8%, P = 0.587).\n The findings from this study suggest that the HDL-C-increasing effect of simvastatin 20 mg is significantly greater than that of atorvastatin 10 mg. Since increasing HDL-C levels is thought to lower the risk for atherosclerosis and coronary heart disease, these results warrant further investigation.", "It has been reported that atorvastatin increases high-density lipoprotein cholesterol (HDL-C) more in patients with low than in those with high baseline HDL-C levels. This may have a biological explanation, but also suggests a statistical artifact known as the regression to the mean.\n Atorvastatin 10 mg/day led to a 4% increase in HDL-C after two months in 67/121 patients with hypercholesterolemia (55%), who had lower baseline HDL-C levels than the patients in whom HDL-C did not increase. In the patients with baseline HDL-C below the median, HDL-C significantly increased whereas no change was observed in patients with baseline HDL-C above the median. The correlation coefficient between pre- and post-treatment HDL-C was 0.84, thus suggesting a regression to the mean. However, the regression artifact did not entirely explain the increase in HDL-C in patients with low baseline HDL-C or the lack of an increase in those with high baseline HDL-C. The adjusted mean increase was 5.4% in patients with low pretreatment HDL-C, and 2.4% in the patients with high pretreatment HDL-C. Multiple regression analysis with the changes in HDL-C as the dependent variable showed that baseline HDL-C and the changes in serum triglycerides independently contributed to the change in HDL-C levels.\n Atorvastatin 10 mg/day increases HDL-C more in patients with low pretreatment HDL-C levels, an effect that seems to be related to the hypotriglyceridemic activity of the drug.", "Clinical trials have demonstrated that, compared with placebo, intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease. However, no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes.\n A total of 893 ambulatory coronary artery disease patients (30% women) 65 to 85 years of age with > or = 1 episode of myocardial ischemia that lasted > or = 3 minutes during 48-hour ambulatory ECG at screening were randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d and followed up for 12 months. The primary efficacy parameter (absolute change from baseline in total duration of ischemia at month 12) was significantly reduced in both groups at month 3 and month 12 (both P<0.001 for each treatment group) with no significant difference between the treatment groups. Atorvastatin-treated patients experienced greater low-density lipoprotein cholesterol reductions than did pravastatin-treated patients, a trend toward fewer major acute cardiovascular events (hazard ratio, 0.71; 95% confidence interval, 0.46, 1.09; P=0.114), and a significantly greater reduction in all-cause death (hazard ratio, 0.33; 95% confidence interval, 0.13, 0.83; P=0.014).\n Compared with moderate pravastatin therapy, intensive atorvastatin therapy was associated with reductions in cholesterol, major acute cardiovascular events, and death in addition to the reductions in ischemia observed with both therapies. The contrast between the therapies' differing efficacy for major acute cardiovascular events and death and their nonsignificant difference in efficacy for reduction of ischemia suggests that low-density lipoprotein cholesterol-lowering thresholds for ischemia and major acute cardiovascular events may differ. The Study Assessing Goals in the Elderly (SAGE) demonstrates that older men and women with coronary artery disease benefit from intensive statin therapy.", "Oxidized-low density lipoproteins (ox-LDL) and the specific receptor LOX-1 are involved in atherogenesis and atherothrombosis. LOX-1 downregulation is associated with the anti-platelet action of atorvastatin. 3'UTR/T LOX-1 polymorphism has been associated with increased risk of coronary artery disease. This study was planned to determine whether LOX-1 genetic variations could affect anti-platelet action of atorvastatin. We studied by platelet P-selectin (P-sel), CD36 and LOX-1 expression (cytofluorimetric detection) whether differences in cellular activation could be suitable in 109 3'UTR/T carriers out of 201 hypercholesterolemic subjects treated with atorvastatin 20mg/day. Hyperactivated platelets (P-sel in resting cells and % variation upon thrombin activation, p<0.001) were detected at baseline in patients without significant differences between T or C carriers. P-sel and platelet-associated ox-LDL, were significantly decreased (all p<0.001) in C carriers after one week of treatment before LDL reduction. In 3'UTR/T carriers P-sel was reduced (p<0.01) after 6 weeks of treatment according to LDL and ox-LDL reduction. In 3'UTR/T carriers atorvastatin reduced platelet activity by LDL and ox-LDL lowering and not by rapid CD36 and LOX-1 downregulation as in C carriers. Such data suggest that in T carriers LDL lowering is needed to achieve anti-platelet action.", "Our study compared use of atorvastatin, fluvastatin, lovastatin, and simvastatin for lowering low-density lipoprotein (LDL) cholesterol concentration in patients at risk for coronary heart disease (CHD). The goal was to reach the LDL cholesterol levels recommended by the National Cholesterol Education Program (NCEP).\n A combined total of 344 men and women took part in this 54-week, multicenter, open-label, randomized, parallel-group, active-controlled, treat-to-target study. Patients were selected on the basis of their LDL cholesterol concentration and their risk for CHD. During treatment, doses were titrated at 12-week intervals to a maximum of 80 mg per day of atorvastatin and lovastatin, or 40 mg per day of fluvastatin and simvastatin, with colestipol added if necessary to attain the NCEP-recommended LDL cholesterol concentration.\n At the starting dose, atorvastatin decreased plasma LDL cholesterol significantly (P < .05) compared with the other reductase inhibitors, and the percentage of patients reaching target LDL cholesterol concentration at the starting dose was significantly greater in the atorvastatin group (P < .05). Overall, a significantly (P < .05) greater percentage (95%) of atorvastatin-treated patients achieved target LDL cholesterol concentration. The safety profile was similar among all reductase inhibitors tested.\n At the starting dose, a significantly (P < .05) greater percentage of atorvastatin-treated patients at risk for CHD reached the target LDL cholesterol concentration than patients with treated with other reductase inhibitors.", "Reduction of platelet activity induced by statins has been described as a positive effect exerted by such molecules on vascular thrombotic events. However, the relations among cholesterol (LDL-C) reduction, the timing of the antiplatelet effect, the involved mechanisms and the doses of each statin able to reduce platelet function are not actually well known. The aim of our study was to evaluate the impact of simvastatin (20 mg day-1), atorvastatin (10 mg day-1), fluvastatin (40 mg day-1) and pravastatin (40 mg day-1) on platelet function in hypercholesterolaemic subjects with relation to (LDL-C), oxidized-LDL (ox-LDL) and antiport mechanism modifications.\n Sixteen subjects were assigned to each treatment (40 males, 24 females, mean age 48.7 +/- 13.4, LDL-C 5.13 +/- 0,23 mmol L-1) and evaluated for platelet surface P-selectin (P-sel), lipid profile, ox-LDL, platelet-associated ox-LDL (Pox-LDL), platelet cholesterol content, antiport mechanisms, and intracellular and systemic NO synthase every 7 days for one month.\n Our data show a strong relation between enhanced P-sel and Pox-LDL (r = 0.68, P < 0.01). Simvastatin, atorvastatin, fluvastatin and pravastatin reduce platelet activity after 1, 2, 3 and 4 weeks of treatment, respectively (P < 0.001, P < 0.001, P < 0.01, P < 0.05). Pox-LDL are modulated early by simvastatin, atorvastatin and fluvastatin Pox-LDL (r = 0.66, 0.65 and 0.52; P < 0.001, 0.001 and 0.01, respectively) whereas LDL-C and ox-LDL reductions associated to modifications of antiport activity act later. Moreover, they are the most relevant finding in pravastatin-related subjects.\n Our data suggest a different impact of several statins on platelet function, which is initially related to interference with Pox-LDL rather than LDL-C reduction.", "The efficacy and safety of rosuvastatin, atorvastatin, and placebo were compared in patients with the metabolic syndrome.\n Patients with the metabolic syndrome with low-density lipoprotein cholesterol (LDL-C) > or =3.36 mmol/L (130 mg/dL) and multiple risk factors conferring a 10-year coronary heart disease risk score of >10% were randomized (2:2:1) to receive rosuvastatin 10 mg, atorvastatin 10 mg, or placebo for 6 weeks. Subsequently, the rosuvastatin 10 mg and placebo groups received rosuvastatin 20 mg and the atorvastatin 10 mg group received atorvastatin 20 mg for 6 weeks. LDL-C was reduced significantly more in patients receiving rosuvastatin 10 mg when compared with those receiving atorvastatin 10 mg at 6 weeks [intention-to-treat (ITT) population by randomized treatment: 41.7 vs. 35.7%, P < 0.001; ITT population by as-allocated treatment: 42.7 vs. 36.6%, P < 0.001]. Significant LDL-C reductions were also observed in patients receiving rosuvastatin when compared with those receiving atorvastatin at 12 weeks (48.9 vs. 42.5%, P < 0.001). More patients achieved LDL-C goals with rosuvastatin when compared with atorvastatin. Rosuvastatin increased high-density lipoprotein cholesterol significantly more than atorvastatin. Treatments were well tolerated.\n At equivalent doses, rosuvastatin had a significantly greater effect than atorvastatin in lowering LDL-C and improving the lipid profile and was well tolerated in patients with the metabolic syndrome.", "Delayed chylomicron clearance is a characteristic of patients with coronary artery disease. In vivo study of the clearance of labeled chylomicron-like emulsions constitutes a valid model system for evaluation of chylomicron catabolism. The effects of atorvastatin at low (10 mg) and high (40 mg) dose upon the intravascular metabolism and plasma kinetics of chylomicron-like emulsions were evaluated in fasting hyperlipidemic subjects (n=45). Subjects were randomized to a 6-week treatment period with placebo (n=15), low dose or high dose atorvastatin (10 mg/day, n=17 and 40 mg/day, n=13). The chylomicron-like emulsion, double-labeled with 14C-Cholesteryl oleate (14C-CE) and 3H-triolein (3H-TG), was injected in a bolus after a 12-h fast, and blood samples were collected up to 60 min. Plasma decay curves were determined for labeled emulsion CE and TG and residence times (RT) calculated by the occupancy principle. The 14C-CE RT was decreased by 50% after low dose atorvastatin and by 73% after atorvastatin at high dose in comparison to placebo (P<0.05). The 3H-TG RT was significantly reduced (-55%) after high dose atorvastatin, but in contrast was not significantly reduced after placebo or low dose statin. By compartmental analysis, both doses of atorvastatin led to marked elevation in the slow removal component of emulsion remnant particles (10 mg/day=107%; 40 mg/day=195%, P=0.01). Equally, the rapid removal component was increased (+99%) at high dose (P=0.015). Recirculation of 3H-fatty acids was significantly reduced at both statin doses (43 and 83%, respectively) in comparison to placebo (P=0.01). In conclusion, atorvastatin treatment accelerates the plasma clearance of chylomicron-like emulsions and reduces recirculation of fatty acids in subjects with atherogenic hyperlipidemia. Such effect might implicate in reduction of cardiovascular risk.", "Hyperlipidemic patients with coronary heart disease were treated with atorvastatin, and its effects on hemostatic and inflammatory parameters were assessed. After 3 months of therapy, the plasma levels of plasminogen activator inhibitor, prothrombin fragment 1+2, highly sensitive C-reactive protein, von Willebrand factor, and fibrinogen were significantly reduced; no significant reductions were observed in lipoprotein(a) and tissue plasminogen activator antigen levels.", "The objective of this study was to examine the effects of treatment with atorvastatin, alpha-tocopherol and the combination of both, on lipoproteins and oxidative stress in dialysis patients.\n This double-blind randomised placebo-controlled trial was performed at the dialysis department of a non-university hospital. SUBJECTS, INTERVENTION AND MEASUREMENTS: A total of 44 clinically stable, non-diabetic patients on dialysis therapy (23 on haemo- and 21 on peritoneal-dialysis) without manifest cardiovascular disease were included in this study. They were randomised for treatment during a period of 12 weeks with 40 mg atorvastatin + placebo alpha-tocopherol (group 1) once daily, 800 IU alpha-tocopherol + placebo atorvastatin once daily (group 2), 40 mg atorvastatin + 800 IU alpha-tocopherol once daily (group 3), or placebo atorvastatin + placebo alpha-tocopherol once daily (group 4). Assessment of lipid profile and oxidative stress was performed at the start of the study and after 12 weeks of treatment.\n Treatment with atorvastatin reduced total cholesterol, triglycerides (TG), low-density lipoprotein (LDL) cholesterol, apolipoprotein B (apoB) and levels of oxidised LDL (oxLDL) with 30-43%. It had no influence on LDL oxidisability. Additional supplementation with alpha-tocopherol had no effect on lipid profile and oxLDL levels but decreased in vitro LDL oxidisability. No side-effects were observed.\n Treatment with atorvastatin is effective in lowering plasma total cholesterol, TG, LDL, apoB and oxLDL in a population of stable dialysis patients and might therefore be an effective tool in improving the poor cardiovascular outcome in these patients. Supplementation of alpha-tocopherol to atorvastatin had beneficial effects on in vitro LDL oxidisability and might therefore be of additional value. Further research on the clinical effects of treatment with atorvastatin in combination with alpha-tocopherol is necessary.", "Endothelial dysfunction represents the earliest stage of atherosclerosis and is usually present in hypercholesterolemia. Treatment with statins has been shown to normalize endothelial function in middle-aged men with hypercholesterolemia. We evaluated the effect over time of atorvastatin on the endothelial reactivity in postmenopausal hypercholesterolemic women (mean age, 58 +/- 6 years), receiving atorvastatin, 10 mg daily (n = 20) or American Heart Association step 1 diet (n = 10) for 8 weeks. Lipid profile and brachial artery flow-mediated vasodilation (FMV) were determined at baseline and after 1, 2, 4, and 8 weeks. FMV increased progressively in subjects treated with atorvastatin, and the difference was significant (p < 0.05 vs. baseline) after the second week (baseline 3.8 +/- 3%; first week, 4.8 +/- 3%; second week, 9.2 +/- 3%; fourth week, 11.0 +/- 3%; eighth week, 11.7 +/- 3%). No significant changes were observed in subjects receiving diet (baseline, 3.1 +/- 4%; first week, 2.4 +/- 2%; second week, 2.9 +/- 2%; fourth week, 3.1 +/- 2%; eighth week, 3.3 +/- 2%; p = NS). In the atorvastatin group, low-density lipoprotein (LDL) cholesterol showed a significant decrease since the first week (baseline, 228 +/- 37 mg/dl; first week, 171 +/- 32; second week, 147 +/- 27; fourth week, 139 +/- 29; eighth week, 135 +/- 27; all p < 0.05). In the control group, LDL cholesterol showed a smaller but significant (p < 0.05) reduction after the second week (baseline, 226 +/- 17 mg/dl; first week, 225 +/- 16; second week, 220 +/- 17; fourth week, 203 +/- 27; eighth week, 198 +/- 27). In conclusion, hypercholesterolemic women treated with atorvastatin show a significant improvement in endothelial reactivity after as early as 2 weeks of therapy. The extent to which these beneficial effects are attributable to cholesterol reduction or to a direct effect of the drug remains to be established.", "The lipid-modifying effects of statin therapy in hypercholesterolemic African-Americans have not been well characterized. This study compared the efficacy and safety of rosuvastatin and atorvastatin treatment for 6 weeks in hypercholesterolemic African-American adults. In the African American Rosuvastatin Investigation of Efficacy and Safety (ARIES) trial (4522US/0002), 774 adult African-Americans with low-density lipoprotein cholesterol > or = 160 and < or = 300 mg/dl and triglycerides < 400 mg/dl were randomized to receive open-label rosuvastatin 10 or 20 mg or atorvastatin 10 or 20 mg for 6 weeks. At week 6, significantly greater reductions in low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B concentrations, as well as lipoprotein and apolipoprotein ratios, were seen with rosuvastatin versus milligram-equivalent atorvastatin doses (analysis of variance with Bonferroni-adjusted critical p < 0.017 for all comparisons). Rosuvastatin 10 mg also increased high-density lipoprotein cholesterol significantly more than atorvastatin 20 mg (p < 0.017). Although statistical comparisons were not performed, larger proportions of rosuvastatin-treated patients than atorvastatin-treated patients achieved National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. The median high-sensitivity C-reactive protein levels were significantly reduced statistically from baseline with rosuvastatin 20 mg and atorvastatin 20 mg among all patients and with rosuvastatin 10 and 20 mg and atorvastatin 20 mg in those patients with a baseline C-reactive protein level > 2.0 mg/L. The 2 study medications were well tolerated during the 6-week study period. In conclusion, rosuvastatin 10 and 20 mg improved the overall lipid profile of hypercholesterolemic African-Americans better than did milligram-equivalent doses of atorvastatin.", "This 6-week Prospective, Randomized, Open-label Blinded End point (PROBE) study conducted at 12 sites in the United States compared the efficacy and safety of atorvastatin with cerivastatin. In all, 215 hypercholesterolemic patients (low-density lipoprotein [LDL] cholesterol > or = 160 mg/dl [4.14 mmol/L]; triglycerides < or = 400 mg/dl [4.52 mmol/L]) were randomized to receive either atorvastatin 10 mg once daily (n = 108) or cerivastatin 0.3 mg once daily (n = 107). Efficacy was assessed by measuring changes from baseline in LDL cholesterol, total cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Atorvastatin produced significantly greater (p < 0.0001) reductions from baseline to week 6 in LDL cholesterol (37.7% vs 30.2%), total cholesterol (27.5% vs 22.2%), and apolipoprotein B (28.6% vs 21.2%), and a significantly greater (p < 0.05) increase from baseline to week 6 in high-density lipoprotein cholesterol (6.8% vs 4.3%) than cerivastatin. Atorvastatin treatment was also associated with a greater percent decrease from baseline to week 6 in triglycerides, with a trend toward statistical significance (p = 0.0982). The percentage of patients that achieved the National Cholesterol Education Program LDL cholesterol goal was greater for those receiving atorvastatin (73%) than for those receiving cerivastatin (66%). The proportion of patients experiencing drug-attributable adverse events, which were mostly mild to moderate and related to the digestive system, was significantly less (p < 0.05) with atorvastatin (5%) than with cerivastatin (14%) treatment. In conclusion, atorvastatin (10 mg/day) is more effective at lowering LDL cholesterol in hypercholesterolemic patients than cerivastatin (0.3 mg/day). Both atorvastatin and cerivastatin are well tolerated, with safety profiles similar to other members of the statin class.", "We sought to determine the effects of oral L-arginine and the hexamethylglutaryl coenzyme A reductase inhibitor atorvastatin on endothelial function in young patients with type I diabetes mellitus (DM).\n Endothelial dysfunction, a key early event in atherosclerosis, occurs in young patients with type I DM, and its reversal may benefit the progression of vascular disease. Cholesterol reduction in L-arginine improve endothelial function in nondiabetic subjects, but their effect in patients with type I DM is unknown.\n In a double-blind, 2x2 factorial study, we investigated the effect of L-arginine (7 g twice daily) and atorvastatin (40 mg/day) on conduit artery vascular function in 84 normocholesterolemic young adults (mean+/-SD: age 34 years [range 18 to 46], low density lipoprotein [LDL] cholesterol 2.96+/-0.89 mmol/liter) with type I DM. Brachial artery dilation to flow (flow-mediated dilation [FMD]) and to the direct smooth muscle dilator glyceryl trinitrate (GTN) were assessed noninvasively using high resolution ultrasound at baseline and after six weeks of treatment.\n Atorvastatin resulted in a 48+/-10% decrease in serum LDL cholesterol levels, whereas L-arginine levels increased by 247+/-141% after L-arginine therapy. By analysis of covariance, treatment with atorvastatin resulted in a significant increase in FMD (p = 0.018. L-Arginine therapy had no significant effect on endothelial function, and there was no significant change in dilation to GTN after either intervention.\n In young patients with type I DM, improvement in endothelial dysfunction can be demonstrated after just six weeks of treatment with atorvastatin. In contrast to studies of hypercholesterolemia, however, L-arginine had no benefit. Treatment with atorvastatin at an early stage may have an impact on the progression of atherosclerosis in these high risk patients.", "Colesevelam hydrochloride is a novel, potent, non-absorbed lipid-lowering agent previously shown to reduce low density lipoprotein (LDL) cholesterol. To examine the efficacy and safety of coadministration of colesevelam and atorvastatin, administration of these agents alone or in combination was examined in a double-blind study of 94 hypercholesterolemic men and women (baseline LDL cholesterol > or =160 mg/dl). After 4 weeks on the American Heart Association Step I diet, patients were randomized among five groups: placebo; colesevelam 3.8 g/day; atorvastatin 10 mg/day; coadminstered colesevelam 3.8 g/day plus atorvastatin 10 mg/day; or atorvastatin 80 mg/day. Fasting lipids were measured at screening, baseline and 2 and 4 weeks of treatment. LDL cholesterol decreased by 12-53% in all active treatment groups (P<0.01). LDL cholesterol reductions with combination therapy (48%) were statistically superior to colesevelam (12%) or low-dose atorvastatin (38%) alone (P<0.01), but similar to those achieved with atorvastatin 80 mg/day (53%). Total cholesterol decreased 6-39% in all active treatment groups (P<0.05). High density lipoprotein cholesterol increased significantly for all groups including placebo (P<0.05). Triglycerides decreased in patients taking atorvastatin alone (P<0.05), but were unaffected by colesevelam alone or in combination. The frequency of side effects did not differ among groups. At recommended starting doses of each agent, coadministration of colesevelam and atorvastatin was well tolerated, efficacious and produced additive LDL cholesterol reductions comparable to those observed with the maximum atorvastatin dose.", "The SR-BI is a key component on the cholesterol metabolism. Polymorphisms in the SR-BI gene (SCARB1) were related with variations on plasma lipoprotein profile and other risk factors for cardiovascular disease. We tested the relationship of 3 SCARB1 single nucleotide polymorphisms (SNPs) with hypercholesterolemia in a Brazilian population and whether these variants can influence lipid-lowering response to atorvastatin.\n c.4G>A, c.726+54C>T and c.1050C>T SNPs and serum concentrations of lipid and apolipoproteins were evaluated in 147 hypercholesterolemic (HC) and 185 normolipidemic (NL) unrelated Brazilian subjects. HC patients were treated with atorvastatin (10 mg/day/4 weeks).\n Frequencies of SCARB1 polymorphisms were similar between the HC and NL groups (p>0.05). The T allele for c.726+54C>T was associated with higher LDL-c in NL and with higher apoB and apoB/apoAI in HC (p<0.05). HC individuals carrying c.1050C allele carriers (CC and CT genotypes) had lower change of total cholesterol, LDL-c, apoB and apoB/apoAI ratio (p<0.05) than the TT genotype carriers in response to atorvastatin.\n The SCARB1 polymorphisms are related with variations in serum lipids in the Brazilian population and c.1050C>T SNP is associated with lipid-lowering atorvastatin response.\n Copyright 2010 Elsevier B.V. All rights reserved.", "The cytochrome P450 isoenzyme 3A5 (CYP3A5) has an important role on biotransformation of xenobiotics. CYP3A5 SNPs have been associated with variations on enzyme activity that can modify the metabolism of several drugs.\n In order to evaluate the influence of CYP3A5 variants on response to lowering-cholesterol drugs, 139 individuals with hypercholesterolemia were selected. After a wash-out period of 4 weeks, individuals were treated with atorvastatin (10 mg/day/4 weeks). Genomic DNA was extracted by a salting-out procedure. CYP3A5*3C, CYP3A5*6 and CYP3A5*1D were analyzed by PCR-RFLP and DNA sequencing.\n >Frequencies of the CYP3A5*3C and CYP3A5*1D alleles were lower in individuals of African descent (*3C: 47.8% and *1D: 55.2%) than in non-Africans (*3C: 84.9% and *1D 84.8%, p<0.01). Non-Africans carrying *3A allele (*3C and *1D combined alleles) had lower total and LDL-cholesterol response to atorvastatin than non-*3A allele carriers (p<0.05).\n CYP3A5*3A allele is associated with reduced cholesterol-lowering response to atorvastatin in non-African individuals.", "Haemorrheological parameters and endothelial function are known to be altered in vascular diseases, including stroke. Treatment with HMG-CoA reductase inhibitors ('statins') improves cerebrovascular (and cardiovascular) morbidity and mortality in patients with atherosclerosis; the beneficial effects may involve lipid-independent mechanisms. The aim of this study was to assess the short-term effect of low-dose atorvastatin on haemorrheological parameters, platelet aggregation and endothelial dysfunction in patients with chronic cerebrovascular disease and hyperlipidaemia.\n Twenty-seven patients (mean age 61 +/- 8 years) with chronic cerebrovascular disease and hyperlipidaemia were included in the study. Serum lipid levels, haemorrheological parameters (haematocrit, plasma fibrinogen levels, plasma and whole blood viscosity [WBV] and red blood cell [RBC] aggregation and deformability) and platelet aggregation were assessed at baseline and after 1 and 3 months of treatment with atorvastatin (Sortis) 10 mg/day. von Willebrand factor (vWF) activity (a measure of endothelial function) was measured at baseline and after 1 month of treatment. Adverse events were recorded at each visit. Physical examinations, haematological assessments and serum and urine chemistry assays were performed during the study.\n Plasma total cholesterol levels were reduced by a mean of 27% compared with baseline after both 1 and 3 months of treatment (p < 0.001). Low density lipoprotein-cholesterol levels were reduced by a mean of 40% and 38% (p < 0.001), respectively, after 1 and 3 months of treatment, compared with baseline values. Triglyceride levels decreased by 20% at 1 month and by 10% after 3 months (p < 0.001). Atorvastatin significantly improved WBV after 3 months of treatment and RBC deformability after 1 month and 3 months of treatment (p < 0.05). Collagen-induced platelet aggregation was significantly decreased at 1 (p < 0.05) and 3 months (p < 0.001) compared with baseline values, despite unaltered antiplatelet therapy. vWF activity was also improved significantly (p < 0.05) after 1 month of treatment.\n Our findings show that the beneficial effects of atorvastatin are complex. Besides lipid lowering, atorvastatin can improve haemorrheological parameters, platelet aggregation and endothelial dysfunction after short-term and low-dose therapy. Whether such early laboratory changes translate into clinical utility for secondary stroke prevention awaits the results of endpoint trials.", "Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is used for lipid-lowering therapy, is an effective statin modulating process involved in atherosclerosis. Paraoxonase (PON) associated with high-density lipoprotein (HDL) has been postulated to have a role in protecting low-density lipoprotein (LDL) against oxidative modification. Oxidation of serum LDL is an important early step in the development of atherosclerosis and auto-antibodies against oxidized LDL (AuAb-oxLDL) reflect in-vivo LDL oxidation.\n To examine the effect of atorvastatin (10 mg/day) therapy on PON activity in serum and HDL, the study group included 40 patients with dyslipidemia (19 women and 21 men), 25 of whom had hypercholesterolemia and of 15 of whom had mixed-type hyperlipidemia. By taking blood samples from the patients, levels of serum lipids, lipid peroxidation product as malondialdehyde (MDA), total antioxidant status (TAS) and AuAb-oxLDL and the activities of PON in serum and isolated HDL were determined.\n The mean levels of total cholesterol, triglyceride, LDL-cholesterol, MDA and AuAb-oxLDL were decreased while HDL-cholesterol and TAS were increased significantly after lipid-lowering therapy in patients with dyslipidemia. On the other hand, PON activities in serum and HDL were increased significantly. The percentage increase in serum PON activity was associated significantly with the percentage decrease in serum AuAb-oxLDL (r=-0.32, P=0.047) and that of HDL PON activity was associated with the percentage increase in HDL-cholesterol level after atorvastatin therapy (r=0.52, P=0.001). The therapy was more effective in increasing PON activity in patients with HDL levels above 35 mg/dl.\n It was concluded that atorvastatin therapy in dyslipidemic patients decreases the level of oxidative stress and increases PON activity, especially in patients with HDL levels above 35mg/dl.", "Coenzyme Q10 (CoQ10) is a provitamin synthesized via the HMG-CoA reductase pathway, and thus may serve as a potential marker of intrinsic HMG-CoA reductase activity. HMG-CoA reductase inhibitors (statins) decrease CoQ10, although it is unclear whether this is due to reductions in lipoproteins, which transport CoQ10.\n We evaluated whether baseline plasma CoQ10 concentrations predict the lipid-lowering response to high-dose atorvastatin, and to what extent CoQ10 changes following atorvastatin therapy depend on lipoprotein changes.\n Individuals without dyslipidemia or known cardiovascular disease (n=84) received atorvastatin 80 mg daily for 16 weeks. Blood samples collected at baseline and after 4, 8, and 16 weeks of treatment were assayed for CoQ10.\n Individuals with higher baseline CoQ10:LDL-C ratios displayed diminished absolute and percent LDL-C reductions at 8 and 16 weeks of atorvastatin treatment (P<0.001 to 0.01). After 16 weeks of atorvastatin, plasma CoQ10 decreased 45% from 762+/-301 ng/ml to 374+/-150 ng/ml (P<0.001). CoQ10 changes were correlated with LDL-C and apolipoprotein B changes (r=0.27-0.38, P=0.001-0.02), but remained significant when normalized to all lipoproteins. CoQ10 changes were not associated with adverse drug reactions.\n Baseline CoQ10:LDL-C ratio was associated with the degree of LDL-C response to atorvastatin. Atorvastatin decreased CoQ10 concentrations in a manner that was not completely dependent on lipoprotein changes. The utility of CoQ10 as a predictor of atorvastatin response should be further explored in patients with dyslipidemia.", "Information of the effect of statin on lipoproteins such as apolipoprotein (apo) A-I, lipoprotein (a) [Lp (a)], or apolipoprotein B levels is limited. This investigation was a crossover study designed to evaluate the efficacy and safety of atorvastatin and simvastatin in patients with hyperlipidemia. Sixty-six patients were involved in the study. Group I consisted of 32 patients, who were first treated with atorvastatin (10 mg) then switched to simvastatin (10 mg). Group II consisted of 34 patients, who were first treated with simvastatin then switched to atorvastatin. Each regimen was used for 3 months (phase I), stopped for 2 months, and then restarted for another 3 months (phase II). Both statins effectively reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), apo B, and Lp (a) (P < 0.001 in all comparisons). A significant increase in the high-density lipoprotein cholesterol (HDL-C) was noted after both statin treatments (P < 0.05 in all comparisons). Both statins caused an increase in the apo A-I levels, and the extent of changes in apo A-I revealed no difference between the two drugs. Compared to the simvastatin group, there were more patients in the atorvastatin group achieving the National Cholesterol Education Program ATP-III LDL-C goal (P < 0.05) and European LDL-C goal (P < 0.001). Both treatments were well tolerated; no patient was withdrawn from the study. This study demonstrates that both statins can effectively improve lipid profiles in patients with hyperlipidemia. Atorvastatin is more effective in helping patients reach the ATP-III and European LDL-C goals than simvastatin at the same dosage.", "We evaluated the antithrombotic effects of statins and angiotensin-converting enzyme inhibitor (ACEI) drugs in patients with coronary artery disease (CAD).\n Blood coagulation at the site of microvascular injury was assessed in 26 males with CAD before and after treatment with quinapril (10 mg day-1; n=13) or atorvastatin (40 mg day-1; n=13) for 4 weeks and an additional 4 weeks of combined therapy (quinapril+atorvastatin). Rates of prothrombin and factor V activation (FVa), fibrinogen (Fbg) cleavage and FVa inactivation showed that both quinapril and atorvastatin decreased the rates of: formation of thrombin B-chain (by 30.6%, P=0.007; and by 34.3%, P=0.003), formation of thrombin-antithrombin complexes (by 30.4%, P=0.0002; and by 40%, P=0.001), FV activation (by 19.1%, P=0.03; and by 21.8%, P=0.005) and Fbg depletion (by 29.2%, P=0.004; and by 32.7%, P=0.001). Atorvastatin alone accelerated FVa inactivation (P=0.005). A further 4 weeks of combined therapy enhanced most anticoagulant effects only when atorvastatin was added to quinapril.\n In CAD patients, atorvastatin and quinapril slowed blood clotting at the site of microvascular injury after 28 days of therapy. Addition of atorvastatin to quinapril, but not quinapril to the statin, enhanced the anticoagulant effects. Our findings might help explain the reduced risk of myocardial infarction or stroke in patients treated with statins and/or ACEIs and the lack of clinical benefits from ACEI added to prior statin therapy in patients at cardiovascular risk.", "A total of 1028 hypercholesterolaemic men and women aged 18-75 participated in an open label, randomised, parallel group, 6-month treatment-to-target study conducted in 240 general practices throughout Australia. The study compared atorvastatin monotherapy with simvastatin monotherapy or, if necessary, with the combination of simvastatin and cholestyramine in terms of their abilities to achieve a plasma total cholesterol target of<5.0 mmol/l. The initial daily dose of each drug was 10 mg. If the target was not achieved, the dose was doubled at 6 week intervals to a maximum daily dose of 80 mg atorvastatin or 40 mg simvastatin, with the simvastatin supplemented if necessary with 4 g cholestyramine. The percentage of patients achieving the target at 10 and 20 mg doses of atorvastatin were comparable to 20 and 40 mg of simvastatin, respectively. Despite relatively high baseline levels of plasma total cholesterol (mean levels of 7.41 and 7.31 mmol/l in the atorvastatin and simvastatin groups, respectively) the majority of patients in each group achieved the plasma total cholesterol target of<5.0 mmol/l. Treatment with atorvastatin achieved the target in 83% of patients, while simvastatin (or simvastatin plus cholestyramine) achieved the target in 66% of the patients (P<0.005). The target was achieved with 10 mg atorvastatin in 38% of patients and with 10 mg simvastatin in 26% of cases (P<0.005). In patients whose baseline cholesterol levels were between 5.6 and 6.5 mmol/l, 95% of the atorvastatin group and 86% of the simvastatin group reached the target. Even with baseline cholesterol levels between 7.6 and 8.5 mmol/l, the target was reached in 78% of the atorvastatin group and 61% of the simvastatin group. It is thus realistic for general practitioners to expect the majority of their at risk patients to achieve target plasma cholesterol levels that have been shown in population studies to be associated with relatively low rates of coronary heart disease. These targets are achieved in significantly more patients and at lower mg doses with atorvastatin than simvastatin.", "Reduction of serum cholesterol levels with statin therapy decreases the risk of coronary heart disease. Inhibition of HMG-CoA reductase by statin results in decreased synthesis of cholesterol and other products downstream of mevalonate, which may produce adverse effects in statin therapy. We studied the reductions of serum ubiquinol-10 and ubiquinone-10 levels in hypercholesterolemic patients treated with atorvastatin. Fourteen patients were treated with 10 mg/day of atorvastatin, and serum lipid, ubiquinol-10 and ubiquinone-10 levels were measured before and after 8 weeks of treatment. Serum total cholesterol and LDL-cholesterol levels decreased significantly. All patients showed definite reductions of serum ubiquinol-10 and ubiquinone-10 levels, and mean levels of serum ubiquinol-10 and ubiquinone-10 levels decreased significantly from 0.81 +/- 0.21 to 0.46 +/- 0.10 microg/ml (p < 0.0001), and from 0.10 +/- 0.06 to 0.06 +/- 0.02 microg/ml (p = 0.0008), respectively. Percent reductions of ubiquinol-10 and those of total cholesterol showed a positive correlation (r = 0.627, p = 0.0165). As atorvastatin reduces serum ubiquinol-10 as well as serum cholesterol levels in all patients, it is imperative that physicians are forewarned about the risks associated with ubiquinol-10 depletion.", "It has been proposed that paraoxonase1 (PON1), a high density lipoprotein (HDL)-associated esterase/lactonase, has anti-atherosclerotic properties. The activity of PON1 is influenced by PON1 polymorphisms. However, the influence of PON1 polymorphisms on PON1 activity and oxidative stress in response to lipid-lowering drugs remains poorly understood. The objective of the present study was to investigate the effects of atorvastatin on PON1 activity and oxidative status. The influence of PON1 polymorphisms on PON1 activity and oxidative status in response to atorvastatin treatment was also evaluated. In total, 22 hypercholesterolemic patients were treated with atorvastatin at a dose of 10 mg/day for 3 months. Lipid profile, lipid oxidation markers (malondialdehyde (MDA), conjugated diene (CD), total peroxides (TP)), total antioxidant substance (TAS), oxidative stress index (OSI), and paraoxonase1 activity were determined before and after treatment. L55M, Q192R, and T(-107)C PON1 polymorphisms were also determined. Atorvastatin treatment significantly reduced the levels of total cholesterol (24.5%), low density lipoprotein (LDL) cholesterol (25.4%), triglycerides (24.4%), CD (4.4%), MDA (15.2%), TP (13.0%) and OSI (24.0%), and significantly increased the levels of TAS (27.3%), and PON1 activity (14.0%). Interestingly, the increase in PON1 activity and the reduction in oxidative stress in response to atorvastatin were influenced only by the PON1 T-107C polymorphism. Atorvastatin treatment improved the lipid profile, lipid oxidation, and oxidative/antioxidative status markers including the activity of PON1 towards paraoxon. These beneficial effects may be attributed to the antioxidant properties of statins and the increase in PON1 activity. The increase in PON1 activity was enhanced by the PON1 T-107C polymorphism.", "C3 complement is produced in response to macrophage activation and is a reliable marker of the risk of myocardial infarction in men. This study was designed to ascertain whether the treatment with atorvastatin, a powerful cholesterol lowering drug, and/or vitamin E, a natural antioxidant, may induce a short term decrease in serum C3 in subjects with persistently elevated levels. From an initial random sample of 1100 men aged 55-64 years, 140 subjects with 3 consecutive C3 measurements in the high tertile (>1.19 g/l) were selected. Those with total cholesterol <5.56 mmol/l were double blindly randomized in groups 1 (placebo, N = 28, G1) and 2 (vitamin E 600 IU/day, N= 30, G2). The subjects with total cholesterol values >5.56 mmol/l were randomized in groups 3 (placebo, N= 30, G3), 4 (atorvastatin 10 mg/day, N = 27, G4) and 5 (atorvastatin 10 mg/day + vitamin E 600 IU/day, N = 25, G5). After 3 months C3 levels were substantially unchanged in the first 4 groups, while in G5 a very significant decrement occurred: -0.070 g/l (5.2%); 95% CI 0.043-0.098; p <0.0001. \"Normal\" levels of C3 (< 1.19 g/l) were reached by 28% of G5 subjects. In G2 and G5 vitamin E levels increased by 60 and 36%, while in G4 they decreased by 23% (p < 0.0001), paralleling cholesterol and triglyceride fall. In all groups a progressive decrease in HDL cholesterol occurred (-17%, p < 0.0001). In conclusion, treatment with atorvastatin plus vitamin E for three months can lower persistently elevated C3 levels.", "This 24-week, randomized, open-label multicenter study evaluated the efficacy and safety of atorvastatin compared with fenofibrate in the treatment of patients with combined hyperlipidemia (CHL). Following a 6-week baseline period, 84 patients with CHL were randomly assigned to either atorvastatin treatment, 10 mg QD for 12 weeks increasing to 20 mg QD for 12 weeks, or fenofibrate treatment, 100 mg TID for 24 weeks. Changes from baseline in lipid parameters were evaluated at weeks 12 and 24. At both 10- and 20-mg doses, atorvastatin treatment resulted in significantly greater reductions in LDL cholesterol, apolipoprotein (apo) B, total cholesterol, LDL-apoB, and lipoprotein-B compared to 300-mg fenofibrate treatment (P < .05). While atorvastatin also resulted in clinically significant reductions in triglyceride, VLDL cholesterol, apoB in VLDL, triglyceride in VLDL, and apoC-III and significant increases in HDL cholesterol and apoA-I levels, fenofibrate was more effective than atorvastatin in altering all these parameters. However, by significantly affecting both the cholesterol-rich and triglyceride-rich particles, atorvastatin holds promise as a lipid-regulator able to adequately treat a broad range of patients that includes those with CHL.", "Myopathy, probably caused by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition in skeletal muscle, rarely occurs in patients taking statins. This study was designed to assess the effect of high-dose statin treatment on cholesterol and ubiquinone metabolism and mitochondrial function in human skeletal muscle.\n Forty-eight patients with hypercholesterolemia (33 men and 15 women) were randomly assigned to receive 80 mg/d of simvastatin (n = 16), 40 mg/d of atorvastatin (n = 16), or placebo (n = 16) for 8 weeks. Plasma samples and muscle biopsy specimens were obtained at baseline and at the end of the follow-up.\n The ratio of plasma lathosterol to cholesterol, a marker of endogenous cholesterol synthesis, decreased significantly by 66% in both statin groups. Muscle campesterol concentrations increased from 21.1 +/- 7.1 nmol/g to 41.2 +/- 27.0 nmol/g in the simvastatin group and from 22.6 +/- 8.6 nmol/g to 40.0 +/- 18.7 nmol/g in the atorvastatin group (P = .005, repeated-measurements ANOVA). The muscle ubiquinone concentration was reduced significantly from 39.7 +/- 13.6 nmol/g to 26.4 +/- 7.9 nmol/g (P = .031, repeated-measurements ANOVA) in the simvastatin group, but no reduction was observed in the atorvastatin or placebo group. Respiratory chain enzyme activities were assessed in 6 patients taking simvastatin with markedly reduced muscle ubiquinone and in matched subjects selected from the atorvastatin (n = 6) and placebo (n = 6) groups. Respiratory chain enzyme and citrate synthase activities were reduced in the patients taking simvastatin.\n High-dose statin treatment leads to changes in the skeletal muscle sterol metabolism. Furthermore, aggressive statin treatment may affect mitochondrial volume.", "Human serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolysing lipid peroxides in oxidized low-density lipoprotein, therefore it may protect against atherosclerosis. One of the two common PON1 gene polymorphisms within the PON1 gene is the Q192R, whose prevalence can be estimated by phenotype distribution analysis. The goal of this study was to clarify the role of PON1 phenotypes on the effect of three different statins on paraoxonase activity and lipid parameters.\n One hundred and sixty-four patients with type IIb hypercholesterolaemia were involved in the study. We examined the effect of 10 mg day(-1) atorvastatin, 10/20 mg day(-1) simvastatin and 80 mg day(-1) extended-release fluvastatin treatment on lipid levels and paraoxonase activity in patients with different PON1 phenotypes. The phenotype distribution of PON1 was determined by the dual substrate method.\n Three months of statin treatment significantly increased paraoxonase activity in every statin-treated group. In patients with AB+BB phenotype, statin treatment was significantly more effective on paraoxonase activity than in the AA group. Statin treatment more effectively decreased triglyceride levels in the AB+BB group compared with the AA group in the whole study population and in the simvastatin-treated group. Atorvastatin treatment was significantly more effective on apolipoprotein B levels in patients with AB+BB phenotype than in the AA phenotype group.\n The PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters.", "Hypercholesterolaemia is associated with a loss of endothelium-dependent vasodilation, which may facilitate the occurrence of myocardial ischaemia in patients with coronary artery disease (CAD). The improvement of endothelial dilator function after 4 to 6 weeks of oral lipid-lowering therapy has been documented. Whether this early restoration of endothelial function by statins translates into anti-ischaemic effects is unknown. This study was designed to determine the effect of 4 weeks' treatment with 80 mg atorvastatin daily on exercise-induced ischaemia in patients with stable ischaemic heart disease (IHD) receiving standard anti-anginal drug therapy.\n A total of 41 patients with documented CAD, exercise-induced ischaemia and LDL-cholesterol > 130 mg/dl underwent exercise ECG, angina score and lipid level assessment at baseline, after 4 weeks of placebo treatment, and after 4 weeks of therapy with atorvastatin 80 mg. Primary endpoint was the change in time to 1 mm ST-segment depression (= ischaemic threshold) between placebo and treatment period. Atorvastatin treatment resulted in a 55% reduction of low-density lipoprotein (LDL) cholesterol (from mean of 162 (SD 32) to 72 (20) mg/dl). For a comparable rate-pressure product, the average time to 1 mm ST-segment depression was 295 (112) s at baseline, 314 (149) s after placebo and 301 (131) s after atorvastatin, indicating that the ischaemic threshold was not significantly modulated after 4 weeks of atorvastatin treatment. There was also no significant change in global angina score or in time to maximal ST-segment depression.\n High-dose atorvastatin treatment for 4 weeks drastically reduced LDL-cholesterol. However, the present study did not demonstrate a significant effect on the ischaemic threshold in patients with stable IHD already under treatment with anti-ischaemic agents.", "Oxidized low-density lipoprotein (oxLDL) is immunogenic while oxidized phospholipids (oxPL) formed on oxLDL and lysophosphatidylcholine (lyso-PC) generated during LDL oxidation through the hydrolysis of oxPL by the lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), significantly contribute to oxLDL immunogenicity. We determined the autoantibody titers against various forms of mildly oxLDL in patients with acute coronary syndromes without persistent elevation of the ST segment (NSTE-ACS) and with undetectable serum levels of lipoprotein (a). Moreover, the effect of early atorvastatin administration on these autoantibody titers was evaluated. From the 133 consecutive NSTE-ACS patients, 55 were eligible for the study. Thirty-four received atorvastatin (group A), whereas 21 did not received any hypolipidemic therapy (group B). Two forms of copper-oxidized LDL were prepared at the end of propagation or decomposition phase (oxLDL(P) or oxLDL(D), respectively). Similar types of oxLDL were prepared after previous inactivation of the endogenous Lp-PLA(2) [oxLDL(-)]. In group B, autoantibody titers of IgG class against oxLDL(P) and oxLDL(D) were elevated at 1 month of follow-up to reach the baseline values 3 months afterwards. By contrast the titers against oxLDL(-)(P) and oxLDL(-)(D) increased at 1 month of follow-up and remained elevated for up to 6 months of follow-up. Atorvastatin treatment prevented the elevation of autoantibody titers against all forms of oxidized LDL. We conclude that a short-term immune response against oxLDL(P) and oxLDL(D) (enriched in lyso-PC) and a chronic immune response against oxLDL(-)(P) and oxLDL(-)(D) (enriched in oxPL) are observed after an NSTE-ACS, suggesting an important role of the LDL-associated Lp-PLA(2) in modulating these immune responses. Early atorvastatin treatment prevents both immune responses; however, the clinical significance of this effect remains to be established.", "Atorvastatin reduces both plasma cholesterol and triglyceride concentrations in patients with type 2 diabetes, but mechanisms underlying triglyceride decrease and the effect of atorvastatin on high density lipoprotein (HDL) still remain unclear. Apolipoprotein (apo) E plays a crucial role in modulating production and clearance of triglyceride-rich very low density lipoprotein (VLDL). The main effect of apoAI is to modulate HDL metabolism. The aim of this work was to study the influence of atorvastatin on apoAI and apoE kinetics and to determine whether its hypocholesterolemic and hypotriglyceridemic effects could be related to changes in this apolipoprotein metabolism. Plasma VLDL-apoE, HDL-apoE, and HDL-apoAI were studied in seven patients with diabetes with mixed hyperlipidemia using a stable isotope labeling technique ([(2)H3]leucine-primed constant infusion) and monocompartmental model before and after 2 months of treatment with 40 mg/day of atorvastatin. Plasma apoE concentration was significantly reduced (44.1 +/- 19.1 versus 32 +/- 11.6 mg/l, p < 0.05) after treatment. This decrease was associated with a diminution of HDL-apoE concentration (17.46 +/- 6.71 versus 13.37 +/- 6.05 mg/l, p < 0.05) and production rate (0.202 +/- 0.085 versus 0.119 +/- 0.047 mg/kg/day, p < 0.05), whereas an increase in VLDL-apoE concentration (6.44 +/- 2.16 before versus 9.23 +/- 4.02 mg/l after, p < 0.05) and production rate (0.827 +/- 0.367 versus 1.524 +/- 0.664 mg/kg/day, p < 0.05) was observed. No significant difference was observed after treatment for apoAI parameters. We conclude that atorvastatin treatment promotes different apoE distribution between HDL and VLDL, favoring VLDL apoE content. The increased number of apoE per VLDL particle suggests that atorvastatin could enhance the direct catabolism of triglyceride-rich VLDL through apoE receptor pathways.", "To compare the long-term efficacy and safety of pitavastatin with atorvastatin in patients with type 2 diabetes and combined (mixed) dyslipidaemia.\n Randomised, double-blind, active-controlled, multinational non-inferiority study. Patients were randomised 2 : 1 to pitavastatin 4 mg (n = 279) or atorvastatin 20 mg (n = 139) daily for 12 weeks. Patients completing the core study could continue on pitavastatin 4 mg (n = 141) or atorvastatin 20 mg (n = 64) [40 mg (n = 7) if lipid targets not reached by week 8] for a further 44 weeks (extension study). The primary efficacy variable was the change in low-density lipoprotein cholesterol (LDL-C).\n Reductions in LDL-C were not significantly different at week 12 between the pitavastatin (-41%) and atorvastatin (-43%) groups. Attainment of National Cholesterol Education Program and European Atherosclerosis Society targets for LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) was similarly high for both treatment groups. Changes in secondary lipid variables (e.g. HDL-C, apolipoprotein B and triglycerides) were similar between treatments. Post hoc analysis showed that adjusted mean treatment differences for pitavastatin vs. atorvastatin were within the non-inferiority margin at weeks 16 (+0.11%; 95% confidence interval (CI), -5.23 to 5.44) and 44 (-0.02%; 95% CI, -5.46 to 5.41) of the extension study. Both treatments were well tolerated; atorvastatin increased fasting blood glucose from baseline (+7.2%; p < 0.05), whereas pitavastatin had no significant effect (+2.1%).\n Reductions in LDL-C and changes in other lipids were not significantly different in patients treated with pitavastatin 4 mg or atorvastatin 20 or 40 mg. Pitavastatin may, however, have a more favourable effect on the glycaemic status.\n © 2011 Blackwell Publishing Ltd.", "At higher doses, simvastatin has been shown to produce significantly greater increases in high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I than atorvastatin. To extend and confirm these findings, a 36-week, randomized, double-blind, dose-titration study was performed in 826 hypercholesterolemic patients to compare the effects of simvastatin and atorvastatin on HDL cholesterol, apo A-I, and clinical and laboratory safety. PRIMARY HYPOTHESIS: Simvastatin, across a range of doses, will be more effective than atorvastatin at raising HDL cholesterol and apo A-I levels.\n A total of 826 hypercholesterolemic patients were enrolled in this double-blind, randomized, parallel, 36-week, dose-escalation study. Patients randomized to simvastatin received 40 mg/day for the first 6 weeks, 80 mg/day for the next 6 weeks, and remained on 80 mg/day for the final 24 weeks. Patients randomized to atorvastatin received 20 mg/day for the first 6 weeks, 40 mg/day for the next 6 weeks, and 80 mg/day for the remaining 24 weeks.\n During the first 12 weeks of the study, simvastatin increased HDL cholesterol and apo A-I more than the comparative doses of atorvastatin, while producing slightly lower reductions in low-density lipoprotein (LDL) cholesterol and triglycerides. At the maximal dose comparison, simvastatin 80 mg and atorvastatin 80 mg, the HDL cholesterol and apo A-I differences favoring simvastatin were larger than at the lower doses. In addition, at the maximal dose comparison, the incidence of drug-related clinical adverse experiences was approximately two-fold higher with atorvastatin 80 mg than with simvastatin 80 mg (23 versus 12%, p < 0.001), due predominantly to a greater incidence of gastrointestinal symptoms with atorvastatin (10 versus 3%, p < 0.001). The incidence of clinically significant alanine aminotransferase elevations was also higher with atorvastatin 80 mg than with simvastatin 80 mg (3.8 versus 0.5%, p < 0.010), especially in women (6.0 versus 0.6%).\n At the doses compared in this study, simvastatin led to greater increases in HDL cholesterol and apo A-I levels than atorvastatin. At the maximum dose comparison, there were fewer drug-related gastrointestinal symptoms and clinically significant aminotransferase elevations with simvastatin.", "To evaluate the effect of atorvastatin in achieving stable sinus rhythm (SR) 30 days after electrical cardioversion (CV) in patients with persistent atrial fibrillation (AF).\n The study included 234 patients. The patients were randomized to treatment with atorvastatin 80 mg daily (n = 118) or placebo (n = 116) in a prospective, double-blinded fashion. Treatment was initiated 14 days before CV and was continued 30 days after CV. The two groups were well-balanced with respect to baseline characteristics. Mean age was 65 +/- 10 years, 76% of the patients were male and 4% had ischaemic heart disease. Study medication was well-tolerated in all patients but one. Before primary endpoint 12 patients were excluded. In the atorvastatin group 99 patients (89%) converted to SR at electrical CV compared with 95 (86%) in the placebo group (P = 0.42). An intention-to-treat analysis with the available data, by randomization group, showed that 57 (51%) in the atorvastatin group and 47 (42%) in the placebo group were in SR 30 days after CV (OR 1.44, 95%CI 0.85-2.44, P = 0.18).\n Atorvastatin was not statistically superior to placebo with regards to maintaining SR 30 days after CV in patients with persistent AF.", "BACKGROUND: The combination of niacin and statin has proven value in hyperlipidemia management and heart disease prevention. However, the efficacy of the non-prescription time-release niacin, Slo-Niacin®, is little studied alone and not at all with atorvastatin. We gave Slo-Niacin® and atorvastatin, singly and together to determine efficacy on the combined abnormalities of triglyceride, LDL and HDL. METHODS: 42 men and women with LDL-C>130mg/dL HDL-C <45 (men or 55mg/dL (women) were randomized to 3 months of atorvastatin 10 mg/day or incremental doses of Slo-Niacin® to 1500 mg/day. The alternate drug was added in the next 3-month segment. Lipid profiles and transaminases were measured monthly and other measures at baseline and the end of each treatment sequence. RESULTS: Mean entry lipids (mg/dL) were: TG 187, LDL-C 171, and HDL-C 39. Mean BMI was 32.6 Kg/m(2). Monotherapy with Slo-Niacin® decreased median triglyceride 15%, mean LDL-C 12% and non-HDL-C 15% and increased HDL-C 8%. Atorvastatin decreased median triglyceride 26%, and mean LDL-C 36%, non-HDL-C 36% and increased HDL-C 6%. Combined therapy decreased median triglyceride 33% and mean LDL-C and non-HDL-C each 43%. HDL-C increased 10% (all p<0.001). Median remnant-like lipoprotein-C decreased 55%, mean apo-B 40%, median hsCRP 23% (all p<0.05), TNFa 12% and no change in IL-6. Mean LDL buoyancy increased 15%, apo-A-I 5% and median HDL(2)-C 20% (all p<0.05). ALT declined with Slo-Niacin® treatment alone compared to atorvastatin and also decreased when Slo-Niacin® was added to atorvastatin. Six subjects dropped out, 3 for niacin related symptoms. CONCLUSIONS: Slo-Niacin® 1.5g/day with atorvastatin 10 mg/day improved lipoprotein lipids, apoproteins and inflammation markers without hepatotoxicity. Slo-Niacin® deserves further study as a cost-effective treatment of hyperlipidemia.", "In this study, we aimed at comparing the effects of standard once daily 20 mg atorvastatin treatment with that of atorvastatin 20 mg administered every other day on serum lipids and high sensitive C-reactive protein (hs-CRP) levels.\n Sixty-one patients with serum total cholesterol levels of above 200 mg/dl and low density lipoprotein (LDL)--cholesterol levels of above 130 mg/dl were included in this prospective, randomized study. The patients were randomized into daily treatment of 20 mg atorvastatin (standard treatment) and 20 mg atorvastatin every other day (every other day treatment) groups. Before the treatment and at each visit, serum lipids and hs-CRP levels of all the patients were measured. Statistical analyses were performed Chi-square, unpaired t and two-way repeated measurements ANOVA tests.\n In the every other day treatment group, there was a 36.1% reduction in LDL-cholesterol levels by the end of first month (p<0.01). At the end of three months there was further decrease of 10.2% in LDL-cholesterol levels when compared to 1 month levels (p>0.05). The LDL cholesterol levels of the group receiving 20 mg atorvastatin every day was reduced by %41 by the end of 1 month (p<0.01). At the end of three months, the difference between the changes in the all lipid parameters of the two groups was not found to be of statistical significance. In the group receiving the medication every other day, there was a 21% decrease in hs-CRP levels compared to the basal measurements at the end of first month (p<0.05). In the group, receiving the medication every day the decrease in hs-CRP levels at the end of one month was more striking (37%, p<0.05). However, the effects of both treatment arms on hs-CRP levels, did not differ significantly (p>0.05).\n Alternate-day dosing of atorvastatin causes a significant lipid-lowering and antiinflammatory effects similar to that of daily administration and yet may provide some cost savings.", "The effect of statins has been monitored mainly in peripheral arteries. It is now possible to study coronary microcirculation by analyzing coronary reserve with transthoracic echocardiography. The aim of this study was to use this noninvasive technique to evaluate the effect of atorvastatin on peripheral endothelial function and on the coronary microvasculature in patients with dyslipidemia.\n We included 21 patients with dyslipidemia but no clinical antecedents of atherosclerosis. Mean (SD) age was 64.9 (11) years, and women made up 61.9% of the group. All patients were treated with 20 mg atorvastatin during 3 months. Lipid profile, carotid intima-media thickness, endothelium-dependent vasodilation and coronary flow reserve were determined at baseline and at the end of treatment. All studies were performed with echocardiographic techniques.\n Together with improvements in the lipid profile, we found a 43% increase in endothelium-dependent vasodilation (4.3 [4.4] to 6.2 [3.8]; P=.07) and a 25% increase in coronary flow reserve (2.5 [0.6] vs 3.1 [0.8]; P=.002). The increase in endothelium-dependent vasodilatation correlated with age (r=-0.60; P=.004), intima-media thickness (r=-0.47; P=.029), low-density lipoprotein level before treatment (r=-0.43; P=.05), and baseline endothelium-dependent vasodilatation (r=-0.63; P=.002). The increase in coronary flow reserve correlated with low-density lipoprotein level after treatment (r=-0.51; P=.04).\n Short-term treatment with atorvastatin improved the lipid profile, coronary microvascular function and endothelium-dependent vasodilation in the peripheral circulation. The noninvasive assessment of coronary reserve is feasible with transthoracic echocardiography.", "To compare the effects of different low-density lipoprotein (LDL) cholesterol-lowering statin treatments on small dense LDL (sd-LDL) in hypercholesterolemic patients with metabolic syndrome (MetS).\n Forty hypercholesterolemic MetS patients ?30 years of age were randomized to rosuvas-tatin (n=17) or other statins (n=23) groups. In the other statins group, those taking atorvastatin (n=12) were also evaluated separately. Statin doses were 10 mg/day rosuvastatin, 20 mg/day atorvas-tatin, 40 mg/day simvastatin, and 40 mg/day pravastatin. Treatment duration was planned to be 8 weeks. Sd-LDL levels were assessed at baseline and at the completion of treatment.\n After treatment, sd-LDL levels were significantly reduced in all 3 groups (from 29.6+/-24.8 mg/dL to 8.9+/-8.5 mg/dL in the rosuvastatin group, p=0.001; from 26.2+/-15 mg/dL to 14.8+/-9.6 mg/dL in the atorvastatin group, p=0.02; and from 29.1+/-16.5 mg/dL to 14.7+/-11.2 mg/dL in the other statins group, p=0.0001). There was no significant difference in the mean percent changes among groups.\n Significant reduction in sd-LDL levels was observed after 8 weeks of statin treatment in hypercholesterolemic patients with MetS. This effect was similar for all statins and can be considered a class effect.", "The authors investigated the time-dependent action of atorvastatin and simvastatin on oxidative stress and cytokine levels immediately after the start of treatment. These factors play a role in endothelial dysfunction. Hyperlipidemic patients (n = 132) were assigned to treatment with 40 mg atorvastatin, 40 mg simvastatin, or placebo. Blood samples were taken before, 2 hours, 24 hours, 7 days, and 3 weeks after the administration of the statin or placebo to evaluate serum concentrations of total peroxides (TP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and soluble intercellular vascular adhesion molecule 1 (sICAM 1). In the atorvastatin group the TP changes were significantly different at 2 hours and 24 hours (p = 0.005), whereas in the simvastatin group there was a gradual, more or less linear decline in TP until 7 days (p = 0.006) and then a plateau. Simvastatin exhibited a faster statistically significant decrease over time in IL-6 and sICAM 1 levels (at 7 days, p = 0.014 and p = 0.001, respectively). TNF-alpha demonstrated a faster linear trend in the simvastatin group, but the significant effect appeared late (p = 0.006). Both simvastatin and atorvastatin exerted early beneficial effects on oxidative stress, proinflammatory cytokines, and endothelial activation in hyperlipidemic subjects. These effects became significant 2 hours following the initiation of therapy.", "Effects independent from cholesterol reduction on vascular function are considered to importantly contribute to the beneficial effects of statin therapy in cardiovascular disease. We aimed to evaluate the effect of high versus low dose atorvastatin on endothelial dysfunction in patients with coronary artery disease (CAD) in a setting of comparable cholesterol reduction.\n Fifty-eight patients with CAD were randomly assigned to double-blind treatment for 8 weeks with atorvastatin 80 mg per day (A80) or atorvastatin 10mg+ezetimibe 10mg per day (A10E10), respectively. Flow-mediated vasodilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent vasodilation (NMD), lipid, C-reactive protein (CRP) plasma concentrations and urinary 8-iso-prostaglandin F2alpha excretion were measured before and after treatment. Total cholesterol, triglycerides and LDL-cholesterol levels were significantly reduced with no difference between A80 and A10E10. A80 caused significantly stronger improvement of FMD compared to A10E10 (absolute change FMD: A80+2.7+/-3.0% (post vs. pre p<0.001), A10E10+0.6+/-2.9% (post vs. pre p=0.25), A80 vs. A10E10 p=0.018). NMD was improved by A80 but not by A10E10 (absolute change NMD: A80+2.7+/-4.6%, A10E10+0.7+/-3.5%, p=0.12). Both treatment groups caused a comparable reduction of CRP and did not effect urinary 8-iso-prostaglandin F2alpha excretion. There was no correlation between FMD or NMD change and LDL-cholesterol change in either treatment group.\n The present findings clearly suggest that in the presence of comparable LDL-lowering effects of both treatment forms, LDL-cholesterol independent effects of high dose atorvastatin therapy account for the improvement of endothelium-dependent vasodilation in patients with stable CAD.", "The beneficial effects of HMG-CoA reductase inhibitors (statins) in patients with coronary artery disease (CAD) appear to be attributable not only to their lipid-lowering properties, but also to their therapeutic effects on the coagulation system, and anti-inflammatory effect. Furthermore, statins mitigate the apoptosis of vascular smooth muscle cells (VSMC) and macrophages in atherosclerotic plaques.\n The purpose of this study was to evaluate the effects of short-term atorvastatin treatment on the fibrinolytic system and systemic inflammatory status, and on apoptosis in hyperlipidemic patients with CAD.\n The study population consisted of 36 hyperlipidemic patients (14 women and 22 men, mean age 53+/-9 years) with stable CAD, untreated with lipid-lowering medications. Serum lipoproteins, fibrinogen levels, sFas and sL-selectin, and global fibrinolytic capacity (GFC) were measured at baseline and after 12 weeks of treatment with atorvastatin, 10 mg/day.\n Atorvastatin treatment decreased serum low-density lipoprotein (-39%, P=0.0001), total cholesterol (-32%, P=0.0001), and triglycerides (-22%, P=0.0001), and increased high-density lipoprotein (+13%, P=0.0001) at 12 weeks compared to baseline. These effects were associated with a decrease in plasma fibrinogen from 331+/-73 to 298+/-58 mg/dl (P=0.0001), and sL-selectin levels from 666+/-201 to 584+/-162 ng/ml (P=0.0001). sFas levels and GFC increased from 3754+/-1264 to 4873+/-1835 pg/ml and from 3.5+/-2.4 to 5.6+/-2.9 microg/ml, respectively (both P=0.0001).\n These results suggest that lipid lowering with atorvastatin therapy significantly increases GFC, decreases fibrinogen levels, and causes leukocyte deactivation. Our findings also suggest that atorvastatin treatment mitigates apoptosis of VSMC in the atherosclerotic plaque. These effects of atorvastatin may, in part, explain the early decrease in cardiovascular events observed in clinical trials of statins.", "Hyperlipidemia is a well established risk factor for cardiovascular disease and atherothrombotic events, in which platelet activation also plays a significant role. However, very few studies have addressed platelet activation in hypercholesterolemia, the potential effect of lipid lowering drugs upon platelet hyperfunction, and the question of whether changes in the latter are correlated to normalization of plasma lipids. This study used whole blood flow cytometry to assess in vivo and in vitro platelet activation in a group of 33 patients with hypercholesterolemia, and also the ex vivo effect of atorvastatin (20 mg/day) upon such activation. A control group of 40 normolipidemic volunteers matched in terms of age, sex and added risk factors to the patient group was used. The results showed that hypercholesterolemic patients had in vivo a significantly greater percentage of GPIIb/IIIa- and phosphatidylserine-positive platelets compared with the control group (4.62+/-3.51% and 2.58+/-1.19% versus 2.73+/-1.08% and 1.54+/-0.68%, respectively). In vitro response of CD62 expression to thrombin was also greater in the patients than in the controls (92.51+/-6.00% versus 89.63+/-10.72%, p<0.05). Atorvastatin therapy normalized platelet hyperfunction in the patients studied and reduced GPIIb/IIIa response to ADP (from 82.65+/-6.43% to 75.84+/-4.89%, p<0.01). A significant correlation can be seen between such normalization and the decrease in plasma levels of total and LDL cholesterol.", "We investigated whether atorvastatin might decrease insulin sensitivity and increase ambient glycemia in hypercholesterolemic patients.\n Clinical trials suggest that some statin treatments might increase the incidence of diabetes despite reductions in low-density lipoprotein (LDL) cholesterol and improvement in endothelial dysfunction.\n A randomized, single-blind, placebo-controlled parallel study was conducted in 44 patients taking placebo and in 42, 44, 43, and 40 patients given daily atorvastatin 10, 20, 40, and 80 mg, respectively, during a 2-month treatment period.\n Atorvastatin 10, 20, 40, and 80 mg significantly reduced LDL cholesterol (39%, 47%, 52%, and 56%, respectively) and apolipoprotein B levels (33%, 37%, 42%, and 46%, respectively) after 2 months of therapy when compared with either baseline (all p < 0.001 by paired t test) or placebo (p < 0.001 by analysis of variance [ANOVA]). Atorvastatin 10, 20, 40, and 80 mg significantly increased fasting plasma insulin (mean changes: 25%, 42%, 31%, and 45%, respectively) and glycated hemoglobin levels (2%, 5%, 5%, and 5%, respectively) when compared with either baseline (all p < 0.05 by paired t test) or placebo (p = 0.009 for insulin and p = 0.008 for glycated hemoglobin by ANOVA). Atorvastatin 10, 20, 40, and 80 mg decreased insulin sensitivity (1%, 3%, 3%, and 4%, respectively) when compared with either baseline (p = 0.312, p = 0.008, p < 0.001, and p = 0.008, respectively, by paired t test) or placebo (p = 0.033 by ANOVA).\n Despite beneficial reductions in LDL cholesterol and apolipoprotein B, atorvastatin treatment resulted in significant increases in fasting insulin and glycated hemoglobin levels consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients. (Effects of Atorvastatin on Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients; NCT00745836).\n Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "In patients with mixed dyslipidemia characterized by increased triglycerides (TG), decreased high-density lipoprotein (HDL) cholesterol, and increased low-density lipoprotein (LDL) cholesterol, monotherapy with lipid-altering drugs often fails to achieve all lipid targets. This multicenter, double-blind, active-controlled study evaluated ABT-335 (fenofibric acid) in combination with 2 doses of atorvastatin in patients with mixed dyslipidemia. A total of 613 patients with LDL cholesterol > or =130 mg/dl, TG > or =150 mg/dl, and HDL cholesterol <40 mg/dl for men and <50 mg/dl for women were randomly assigned to ABT-335 (135 mg), atorvastatin (20, 40, or 80 mg), or combination therapy (ABT-335 + atorvastatin 20 or 40 mg) and treated for 12 weeks. Combination therapy with ABT-335 + atorvastatin 20 mg resulted in significantly greater improvements in TG (-45.6% vs -16.5%) and HDL cholesterol (14.0% vs 6.3%) compared with atorvastatin 20 mg and LDL cholesterol (-33.7% vs -3.4%) compared with ABT-335. Similarly, significantly greater improvements were observed with ABT-335 + atorvastatin 40 mg in TG (-42.1% vs -23.2%) and HDL cholesterol (12.6% vs 5.3%) compared with atorvastatin 40 mg and LDL cholesterol (-35.4% vs -3.4%) compared with ABT-335 monotherapy. Combination therapy also improved multiple secondary variables. Combination therapy was generally well tolerated with a safety profile consistent with those of ABT-335 and atorvastatin monotherapies. No rhabdomyolysis was reported. In conclusion, ABT-335 + atorvastatin combination therapy resulted in more effective control of multiple lipid parameters than either monotherapy and may be an appropriate therapy for patients with mixed dyslipidemia.", "Hyperhomocysteinemia is regarded as an independent risk factor for cardiovascular disease. Lipid-lowering agents, such as fibrates, can modify homocysteine levels. However, less is known about the effect of statin therapy on homocysteine. The authors compared the effects of atorvastatin (40 mg/day), simvastatin (40 mg/day), and micronized fenofibrate (200 mg/day) on the serum concentrations of total homocysteine, vitamin B12, and folic acid in patients with primary hyperlipidemia. A total of 128 patients with primary hyperlipidemia (total cholesterol > 240 mg/dL and triglycerides < 350 mg/dL) were assigned to atorvastatin, simvastatin, or fenofibrate. Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment. Homocysteine correlated positively with serum creatinine and uric acid levels and inversely with serum folic acid levels. All treatment modalities reduced total, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations. High-density lipoprotein (HDL) cholesterol levels significantly increased only in the fenofibrate-treated patients (47.9 +/- 12.5 vs. 50.7 +/- 12.6 vs. 51.2 +/- 12.8 mg/dL, p < 0.01). Atorvastatin and fenofibrate treatment resulted in a significant reduction of serum uric acid levels (5.3 +/- 1.6 vs. 4.9 +/- 1.4 vs. 4.8 +/- 1.4 mg/dL, p < 0.0001 for atorvastatin; 5.6 +/- 1.6 vs. 4.3 +/- 1.4 vs. 4.4 +/- 1.4 mg/dL, p < 0.0001 for fenofibrate). Homocysteine levels were significantly increased only by fenofibrate (10.3 +/- 3.3 vs. 14.1 +/- 3.8 vs. 14.2 +/- 3.6 microU/L, p < 0.001) but did not change from baseline following statin treatment. Neither statins nor fenofibrate had any effect on serum vitamin B12 and folic acid levels. In contrast to fenofibrate, therapeutic dosages of atorvastatin and simvastatin have a neutral effect on serum homocysteine levels, which is in favor of their \"cardioprotective\" properties.", "Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study was conducted to test the efficacy and safety of atorvastatin, a new synthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week placebo phase, 22 subjects were randomized to either 80 mg atorvastatin at night (n = 11) or 40 mg twice a day for 6 weeks. The two dosage groups were well matched and had no difference in lipoprotein responses. After 6 weeks, the LDL cholesterol concentration was reduced by 57%, from 8.16 +/- 1.15 to 3.53 +/- 0.99 mmol/L (P < .001). The total cholesterol concentration decreased from 9.90 +/- 1.32 to 5.43 mmol/L (P < .001). HDL cholesterol concentration increased from 1.19 +/- 0.31 to 1.49 +/- 0.43 mmol/L (P < .001). Triglyceride concentrations decreased from 1.34 +/- 0.66 to 0.88 +/- 0.36 mmol/L (P < .01). Three subjects had single, transient increases of serum transaminase of up to twice the upper limit of normal. Apolipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nondenaturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentration increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Atorvastatin is a powerful and safe lipid-modifying agent for LDL cholesterol; it also modifies HDL cholesterol and triglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH.", "The aim of our study was to examine the influence of atorvastatin on lipid parameters, particularly on HDL, and on the activity of LCAT and CETP and how they affect the activity of the HDL-associated antioxidant enzyme paraoxonase.\n Thirty-three patients with types II.a and II.b primary hyperlipoproteinemia were enrolled into our study. The patients received atorvastatin, 20 mg daily, for 3 months. We measured the serum paraoxonase activity and concentration, oxidized LDL, LCAT and CETP activities.\n Atorvastatin significantly reduced the levels of cholesterol, triglyceride, LDL-C and apoB, while it did not influence the levels of HDL-C and apo A-I. The increases in serum PON-specific activity, PON/HDL ratio and LCAT activity were significant, while oxLDL and CETP activities were significantly decreased.\n Atorvastatin may influence the composition and function of HDL, thereby possibly increasing the activity of paraoxonase and preventing atherosclerosis.", "Hypercholesterolemic patients with metabolic syndrome (MS) are at high risk for coronary heart disease. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines provide the option of aggressively lowering low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients with MS.\n The lipid-modifying efficacy of simvastatin and atorvastatin in hypercholesterolemic patients with MS as defined by NCEP ATP III was assessed.\n A post hoc subgroup analysis was performed on data from a 36-week, multicenter (54 sites worldwide), randomized, double-blind, parallel-group, dose-escalation (forced-titration) study designed to assess the effects of simvastatin (40-80 mg) and atorvastatin (20-80 mg) on high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I levels in patients with LDL-C > or = 160 mg/dL. Patients were classified as having MS if they met >/=3 of the following criteria: (1) triglyceride (TG) level > or =150 mg/dL; (2) HDL-C <40 mg/dL (men) or <50 mg/dL (women); (3) secondary diagnosis of type 2 diabetes mellitus and/or taking antidiabetic medication and/or fasting serum glucose (FSG) level > or =110 mg/dL; (4) secondary diagnosis of hypertension and/or taking antihypertensive medication and/or systolic blood pressure (SBP)/diastolic blood pressure (DBP) > or =130/ > or =85 mm Hg; and (5) body mass index (BMI) > or =30 kg/m(2) (surrogate for waist circumference).\n Of 808 evaluable patients, 212 (26.2%) were classified as having MS at baseline. Compared with the non-MS subgroup, MS patients were slightly older and more likely to be female. They also had higher BMI, SBP/DBP, FSG, and TG levels, and lower HDL-C and apo A-I levels than non-MS patients. The simvastatin group contained 99 patients; the atorvastatin group, 113 patients. Both drugs produced large reductions in total cholesterol, LDL-C, non-HDL-C, TG, and apo B, with atorvastatin producing slightly greater reductions in TG. However, simvastatin consistently produced larger increases in HDL-C and apo A-I than atorvastatin, especially at higher doses. After 36 weeks of treatment, 47.7% and 48.5% in the simvastatin and atorvastatin groups, respectively, no longer met > or =3 of the MS criteria.\n In hypercholesterolemic patients with characteristics of MS, simvastatin and atorvastatin had comparable beneficial effects on apo B-containing atherogenic lipids and lipoproteins, and MS status was effectively modified by both drugs. However, although atorvastatin produced slightly larger decreases in TG, simvastatin produced larger increases in HDL-C.", "Recent studies have demonstrated that women at high risk for cardiovascular disease (CVD) benefit from cholesterol lowering to an extent similar to that of men. The ability to achieve established treatment goals for low-density lipoprotein cholesterol (LDL-C) in women with clearly defined risk factors has not been examined in detail.\n We have determined the efficacy and frequency of achieving target levels for LDL-C with atorvastatin on the basis of National Cholesterol Education Program Adult Treatment Panel II recommendations in 318 women according to the presence of CVD (198 women) or risk factors for CVD (120 women) and the presence of mixed dyslipidemia with obesity with or without CVD (72 women). Mean baseline LDL-C concentrations for women with established CVD were in the upper 10% of the distribution for age-matched North American women and, for those without CVD, were also extremely elevated and were in the top 5% of the LDL-C distribution for age-matched women in this population. The majority of participants without CVD (63%) reached LDL-C targets (LDL-C <or=160 mg/dL [4.1 mmol/L] if <2 CHD risk factors and LDL-C <or=130 mg/dL [3.4 mmol/L] if >or=2 CVD risk factors) with 10 mg atorvastatin and 79% reached targets with up to 20 mg of atorvastatin. For women with established CVD, 34% achieved an LDL-C <or=100 mg/dL (2.6 mmol/L) with 10 mg and 60% reached this target with up to 20 mg of atorvastatin. With maximal titration to the LDL-C target, up to and including 80 mg atorvastatin, 87% of women without CVD and 80% of women with established CVD achieved LDL-C targets. The presence of mixed dyslipidemia with obesity did not affect the frequency of achieving LDL-C targets.\n Atorvastatin is very effective in achieving National Cholesterol Education Program Adult Treatment Panel II target concentrations for LDL-C in the majority of women with established CVD or CVD risk factors.", "Emerging evidence suggests that statins have a favorable impact on the reduction of arrhythmia events and sudden cardiac death in patients with structural heart disease. We aimed to investigate the possibly and directly favorable effects of statins on ventricular late potentials, QT dispersion, and transmural dispersion of repolarization attained by analyzing clinical electrocardiography (ECG) risk stratification parameters in patients with hypercholesterolemia without structural heart disease. In total, 82 patients (45 females; mean age, 62 +/- 10 years) with hypercholesterolemia were enrolled in this prospective study to examine the effects of statin therapy (atorvastatin 10 mg/day for 3 months) on ECG risk stratification parameters. Surface 12-lead ECG and signal-average ECG (SAECG) were recorded before and after statin treatment. The SAECG parameters, QT dispersion, Bazett-corrected QT (QTc) dispersion, T wave peak-to-end interval (Tpe), and percentage of Tpe/QT interval were calculated and compared before and after statin therapy. Twelve-lead ambulatory 24-hour ECGs were recorded in 12 patients. The results demonstrated that after statin therapy for 3 months, serum levels of total cholesterol and low-density lipoprotein cholesterol were significantly reduced (both p values < 0.001). However, neither significant changes of each SAECG parameter nor the frequency of late potentials were demonstrated after atorvastatin therapy. In addition, no significant changes in QT dispersion, QTc dispersion, Tpe, or Tpe/QT were found. However, 24-hour ambulatory ECG revealed a flattening effect of circadian variation of QTc dispersion after atorvastatin therapy. In conclusion, the favorable antiarrhythmia effect of atorvastatin (10 mg/day) therapy cannot be directly reflected by analyzing these noninvasive ECG risk stratification parameters in low-risk patients with hypercholesterolemia.", "The effects of atorvastatin (lipitor) on cholesterol-rich and triglyceride-rich lipoproteins were evaluated in this multicenter trial. Following a 6-week baseline period, 47 patients with elevated cholesterol and triglyceride levels were treated with atorvastatin 10 mg once daily (QD) for the initial 12 weeks (Period 1) increasing to 20 mg QD for the following 12 weeks (Period 2). At both the 10 and 20 mg doses, atorvastatin treatment resulted in significant reductions compared to pretreatment levels in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein (apo) B, apoB in LDL (LDL-apo B), apo B in VLDL (VLDL-apo B), lipoprotein (Lp)B, lipoprotein B-complex (LpBc), triglycerides (TG), low-density lipoprotein triglycerides (LDL-TG), very low-density lipoprotein triglyceride (VLDL-TG), high-density lipoprotein triglycerides (HDL-TG), and apo C-III. Atorvastatin 10 and 20 mg QD also resulted in significant increases in high-density lipoprotein cholesterol (HDL-C), apo AI, and LpAII:B:C:D:E. Due to its unique ability to normalize both cholesterol-rich and triglyceride-rich particles, atorvastatin is a promising candidate for monotherapy in a broad range of patients including those with varying degrees of hypercholesterolemia and hypertriglyceridemia.", "HMG-CoA reductase inhibitors or statins are effective in both the primary and secondary prevention of coronary heart disease, the extent of benefit being proportional to the reduction in low density lipoprotein (LDL) cholesterol achieved. Atorvastatin, a newly licensed compound, reportedly lowers LDL with greater efficacy than other statins. The mechanism of this action was, therefore, explored in twenty patients with refractory familial hypercholesterolemia who received in a single-blind sequence simvastatin 40 mg/day, placebo and atorvastatin 10 mg/day each for 4 weeks. At the end of the placebo period the effects of single 40-mg doses of simvastatin and atorvastatin on plasma levels and urinary excretion of mevalonic acid, indices of HMG-CoA reductase activity, were compared. Administration of atorvastatin 10 mg daily for 1 month lowered LDL cholesterol by 32.5%, compared with placebo (P = 0.0001), which was 4.5% less than the decrease after simvastatin 40 mg daily (P = 0.33). The area under the plasma curve and urinary mevalonic acid/ creatinine ratio were both significantly less during the 24 h after a single dose of atorvastatin 40 mg than after a single dose of simvastatin 40 mg (P < 0.01). These findings suggest that the greater efficacy of atorvastatin compared with simvastatin is due to more prolonged inhibition of HMG-CoA reductase, presumably reflecting longer residence of atorvastatin or its active metabolites in the liver.", "Atherogenesis involves the migration of leukocytes into vascular subendothelial space, a process mediated by endothelial and leukocyte cell adhesion molecules. Endothelial molecules are assessed indirectly via serum levels, but leukocyte molecules can be assessed directly. We have therefore hypothesized that leukocyte adhesion molecules are altered to a greater degree in hypercholesterolemia than serum endothelial adhesion molecules. We examined 29 subjects with hypercholesterolemia and 27 controls at baseline and after 12 weeks of atorvastatin treatment (20 mg/day). Expression of leukocyte integrins CD11a, CD11b, CD18, and CD49d and of L-selectin was measured by flow cytometry. Serum ICAM-1, E-selectin and von Willebrand factor were measured by ELISA. Expression of leukocyte adhesion molecules was significantly higher in patients at baseline than in the controls, except for CD11a. Expression significantly decreased after atorvastatin in most adhesion molecules except for CD11b. In contrast, there was no effect of hypercholesterolemia and/or atorvastatin on the serum endothelial molecules. Leukocyte but not endothelial adhesion molecules were influenced by hypercholesterolemia and by lipid lowering treatment. Leukocyte molecules may therefore be a more sensitive marker of atherogenesis than endothelial molecules. Our results support the role of increased leukocyte adhesiveness in atherogenesis.", "The aim of this study was to compare the effects of 3 different statin regimens that have equivalent low-density lipoprotein cholesterol (LDL-C) lowering efficacy on the apolipoprotein B/A1 ratio and glucose metabolism. After a 4-week dietary lead-in, 90 hypercholeserolemic patients were randomly assigned to 1 of 3 treatment groups for 8 weeks: atorvastatin 20 mg, rosuvastatin 10 mg, or atorvastatin/ezetimibe 5 mg/5 mg. At drug treatment week 8, we compared the percentage changes in lipid parameters, apolipoprotein B/A1 ratio, hemoglobin A1c, and homeostasis model assessment-insulin resistance (HOMA-IR) from baseline. Seventy-six patients completed the study and the percentage changes in LDL-C were comparable among the groups. However, the percentage reduction in the apolipoprotein B/A1 ratio was significantly greater in the rosuvastatin group (-47% +/- 14%, P = .04) and the combination group (-46% +/- 8%, P = .05) than in the atorvastatin group (-39% +/- 11%). The percentage increase in hemoglobin A1c was small but significantly greater in the atorvastatin group compared to the combination group (3.0% +/- 5.2% and -0.4% +/- 4.0%, P = .03). The effect of rosuvastatin on hemoglobin A1c was not different from those of the other 2 regimens. The effects of 3 statin regimens were similar on HOMA-IR. In conclusion, 3 statin regimens have differential effect on apolipoprotein B/A1 and glycemic control after comparable LDL-C reduction.", "A randomized, blinded, multicenter clinical trial was performed comparing low- and high-dose simvastatin (40 and 80 mg) with comparable doses of atorvastatin (20 and 40 mg) for effects on plasma concentrations of lipoproteins and apolipoprotein A-I over 12 weeks in 842 patients with elevated low-density lipoprotein cholesterol. The 2 agents reduced low-density lipoprotein cholesterol and triglycerides to a comparable degree, but simvastatin raised high-density lipoprotein cholesterol and apolipoprotein A-I more than atorvastatin, suggesting differences in metabolic effects of the 2 agents on plasma lipids and lipoproteins.", "Statin therapy may target both hypercholesterolemia and cholestasis in primary biliary cirrhosis (PBC). However, little is known about the efficacy and safety of statins in PBC. The aim of this single-center study was therefore to prospectively examine the effects of atorvastatin on serum markers of cholestasis, aminotransferases, and lipid and bile acid metabolism as well as inflammatory and immunological markers in patients with PBC. Fifteen patients with early-stage PBC and an incomplete biochemical response to ursodeoxycholic acid (UDCA) therapy (defined as alkaline phosphatase 1.5-fold above the upper limit of normal after 1 year) were treated with atorvastatin 10 mg/day, 20 mg/day, and 40 mg/day for 4 weeks, respectively. Serum levels of alkaline phosphatase increased during atorvastatin 20 mg and 40 mg (P < 0.05), whereas leucine aminopeptidase and gamma-glutamyltransferase remained unchanged. No statistical differences in overall serum ALT, AST, bilirubin, and IgM levels were observed. However, atorvastatin was discontinued in 1 out of 15 patients because of ALT 2-fold above baseline, and 2 patients showed ALT elevations 3-fold above the upper limit of normal at the end of the atorvastatin treatment period. Serum total cholesterol and low-density lipoprotein cholesterol levels decreased by 35% and 49%, respectively (P < 0.001). Precursors of cholesterol biosynthesis (lanosterol, desmosterol, lathosterol) showed a similar pattern. No changes in serum bile acid levels and composition were observed during treatment.\n Atorvastatin does not improve cholestasis in PBC patients with an incomplete biochemical response to UDCA but effectively reduces serum cholesterol levels.", "C-reactive protein (CRP) levels are associated with cardiovascular risk. We assessed the hypothesis that atorvastatin might have anti-inflammatory effects in acute coronary syndromes (ACS) as shown by CRP reduction.\n This study was a prospective, randomized, double-blind, placebo-controlled study of 90 consecutive patients admitted within 48 hours of onset of ACS with CRP levels > or =1.4 mg/dL. Patients were assigned to atorvastatin 40 mg daily or placebo over 30 days. C-reactive protein levels, lipid profiles, serum fibrinogen, white cell count, and erythrocyte sedimentation rate were measured at entry, hospital discharge, and 1 month later.\n Baseline clinical characteristics did not differ between atorvastatin and placebo groups (mean age 59.3 +/- 13.4 vs 61.1 +/- 11.5, P = ns); myocardial infarction 52.3% versus 67.4% ( P = ns). In both groups, median baseline CRP levels were comparable (5.97 +/- 6.2 vs 4.64 +/- 4.2 mg/dL, P = ns). C-reactive protein levels were lower in the atorvastatin group versus control group at discharge (1.68 +/- 1.65 vs 4.12 +/- 4.18 mg/dL) and at 30 days (0.50 +/- 0.71 vs 2.91 +/- 2.68 mg/dL, both P < .0001). C-reactive protein levels significantly decreased from baseline to discharge and 1 month later in placebo and atorvastatin groups (both P < .0001); however, the reduction was greater in the atorvastatin group (62% vs 11% at discharge [P < .0001]; 84% vs 30% at 1 month [P < .0001]). In addition, atorvastatin was associated with a reduction in total and low-density lipoprotein cholesterol and erythrocyte sedimentation rate at discharge and at 30 days (P < .0001 for all comparisons). No correlation was found between changes in CRP and cholesterol levels.\n C-reactive protein levels in ACS were rapidly reduced with atorvastatin. These data provide evidence that statins have fast and early anti-inflammatory effects in addition to lipid-lowering effects in ACS.", "The objective of this multicenter, randomized, open-label, parallel-group, 8-week study was to evaluate the comparative dose efficacy of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin 10, 20, 40, and 80 mg compared with simvastatin 10, 20, and 40 mg, pravastatin 10, 20, and 40 mg, lovastatin 20, 40, and 80 mg, and fluvastatin 20 and 40 mg. Investigators enrolled 534 hypercholesterolemic patients (low-density lipoprotein [LDL] cholesterol > or = 160 mg/dl [4.2 mmol/L] and triglycerides < or = 400 mg/dl [4.5 mmol/L]). The efficacy end points were mean percent change in plasma LDL cholesterol (primary), total cholesterol, triglycerides, and high-density lipoprotein cholesterol concentrations from baseline to the end of treatment (week 8). Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01) reductions in LDL cholesterol, -38%, -46%, and -51%, respectively, than the milligram equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin. Atorvastatin 10 mg produced LDL cholesterol reductions comparable to or greater than (p < or = 0.02) simvastatin 10, 20, and 40 mg, pravastatin 10, 20, and 40 mg, lovastatin 20 and 40 mg, and fluvastatin 20 and 40 mg. Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01) reductions in total cholesterol than the milligram equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin. All reductase inhibitors studied had similar tolerability. There were no incidences of persistent elevations in serum transaminases or myositis.", "Higher than 80% of coronary heart disease-related mortality occurs in patients ≥65 years of age. Guidelines recommend low-density lipoprotein (LDL) cholesterol targets for these at-risk patients; however, few clinical studies have evaluated lipid-lowering strategies specifically in older adults. This multicenter, 12-week, randomized, double-blind, parallel-group trial evaluated the efficacy and safety of the usual starting dose of ezetimibe/simvastatin (10/20 mg) versus atorvastatin 10 or 20 mg and the next higher dose of ezetimibe/simvastatin (10/40 mg) versus atorvastatin 40 mg in 1,289 hypercholesterolemic patients ≥65 years of age with or without cardiovascular disease. Patients randomized to ezetimibe/simvastatin had greater percent decreases in LDL cholesterol (-54.2% for 10/20 mg vs -39.5% and -46.6% for atorvastatin 10 and 20 mg, respectively; -59.1% for 10/40 mg vs -50.8% for atorvastatin 40 mg; p <0.001 for all comparisons) and the number attaining LDL cholesterol <70 mg/dl (51.3% for 10/20 mg, 68.2% for 10/40 mg) and <100 mg/dl (83.6% for 10/20 mg; 90.3% for 10/40 mg) was significantly larger compared to those receiving atorvastatin for all prespecified dose comparisons (p <0.05 to <0.001). A significantly larger percentage of high-risk patients achieved LDL cholesterol <70 mg/dl on ezetimibe/simvastatin 10/20 mg (54.3%) versus atorvastatin 10 mg (10.9%, p <0.001) or 20 mg (28.9%, p <0.001) and ezetimibe/simvastatin 10/40 mg (69.2%) versus atorvastatin 40 mg (38.2%, p <0.001), and a significantly larger percentage of intermediate-risk patients achieved LDL cholesterol <100 mg/dl on ezetimibe/simvastatin 10/20 mg (82.1%) versus atorvastatin 10 mg (59.3%, p <0.05). Improvements in non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and lipoprotein ratios were significantly greater with ezetimibe/simvastatin than atorvastatin for all comparisons (p <0.01 to <0.001). High-density lipoprotein cholesterol and triglyceride results were variable. All treatments were generally well tolerated. In conclusion, ezetimibe/simvastatin provided significantly greater improvements in key lipid parameters and higher attainment of LDL cholesterol targets than atorvastatin, with comparable tolerability.\n Copyright © 2010 Elsevier Inc. All rights reserved.", "Many of the pleiotropic effects of statins remain to be elucidated.\n Different statin regimens with similar lipid-lowering efficacy may have different effects on biomarkers of atherothrombosis including lipoprotein-associated phospholipase A₂ (Lp-PLA₂ ).\n After a 4-week dietary lead-in, 82 hypercholesterolemic patients were randomized to 1 of 2 treatment groups: atorvastatin 20 mg or atorvastatin/ezetimibe 5 mg/5 mg. After 8 weeks of drug treatment, the groups were compared for percent change in lipid parameters, Lp-PLA₂ , interleukin-6 (IL-6), monocyte chemoattractant protein-1, and fibrinogen.\n Low-density lipoprotein cholesterol (LDL-C) lowering was comparable between the 2 groups (-47% ± 11% and -49% ± 7% in the atorvastatin and combination groups, respectively). Although Lp-PLA₂ was reduced in both groups, the reduction was greater in the atorvastatin group (-42% and -9% [median], respectively, P = 0.03). Although IL-6 was decreased only in the atorvastatin group, IL-6 changes were not significantly different between the 2 groups. The changes in monocyte chemoattractant protein-1 and fibrinogen were similar in each group.\n Atorvastatin monotherapy was stronger at reducing plasma Lp-PLA₂ than the low-dose atorvastatin/ezetimibe combination after equivalent LDL-C lowering. This result may provide evidence of potential statin effects beyond the lowering of LDL-C.\n © 2011 Wiley Periodicals, Inc.", ". The beneficial effects of statins on clinical events may involve mechanisms that modify endothelial dysfunction, plaque stability, thrombus formation, and inflammatory responses. To determine the effect of atorvastatin on blood rheology in patients with familial hypercholesterolemia (FH), we prospectively studied serum lipid concentration, red cell cholesterol content, lipid peroxidation and erythrocyte membrane fluidity. The aim of this paper was to evaluate the effects of atorvastatin therapy on the erythrocyte membrane structure and the hypolipemic efficacy in patients with FH. MATERIALS, METHODS AND SUBJECTS STUDIED:. The study involved 31 patients with FH and 20 healthy individuals as a control group. The program lasted 20 weeks. For the first 8 weeks, the patients were on a hypolipemic diet only and for the subsequent 12 weeks, alongside the diet they were given 10 mg atorvastatin per day. Laboratory tests were carried out before and after 4 weeks and 12 weeks of the pharmacological treatment. Erythrocyte membrane fluidity was determined using the spin labeled method. The peroxidation of lipids was measured in whole erythrocytes as well as in erythrocyte plasma membranes by means of the thiobarbituric acid technique.\n . Treatment with atorvastatin reduced serum total cholesterol concentration from 310+/-29 mg/dl in a basal situation to 203+/-34 mg/dl ( P<0.001) at the end of the treatment and low-density lipoprotein (LDL) cholesterol concentration from 225+/-30 mg/dl to 126+/-30 mg/dl ( P<0.001), respectively. The changes observed in the plasma lipids correlate with a significant decrease in erythrocyte membrane cholesterol, from 2.24+/-1.69 to 1.17+/-0.75 mg/mg protein ( P<0.001) after 12 weeks of treatment. The lipid peroxidation in membranes of erythrocytes was lowered from the basal value 0.171+/-0.097 to 0.100+/-0.024 mmol/mg protein ( P<0.05) after 4 weeks of treatment and to 0.057+/-0.020 mmol/mg protein ( P<0.001) after 12 weeks of treatment, and in total erythrocytes from 4.78+/-1.49 to 3.99+/-1.39 mmol/g Hb ( P<0.02) and 2.43+/-0.87 mmol/g Hb ( P<0.001), respectively. The membrane fluidity was estimated by means of parameter S at the depth of the fifth carbon atom. Atorvastatin in hypercholesterolemic erythrocytes enhances the fluidity of the superficial layer from 0.758+/-0.009 up to the values observed in the control group 0.744+/-0.009 ( P<0.001). There is no impact on the microviscosity of the hydrophobic core observed.\n . Our findings suggest that the atorvastatin therapy reverses the alteration of erythrocyte plasma membrane properties. It may improve blood rheology in patients with FH. This improvement in blood properties may contribute to the well-known beneficial effects of atorvastatin on cardiovascular risk in patients with severe hyperlipidemia and atherosclerotic vascular disease.", "Patients with end-stage renal disease commonly present with an atherogenic lipid profile characterized by the accumulation of triglyceride-rich, apoprotein B-containing \"remnant\" lipoproteins, small dense low-density lipoprotein, and low levels of high-density lipoprotein. They are at increased cardiovascular risk and may benefit from drastic lipid-lowering treatment with atorvastatin, a potent, broadacting lipid regulator. This study aims to assess the effects of atorvastatin on the lipid profile in hemodialysis patients, to determine wether atorvastatin is also effective at lowering lipid levels in this particular high-risk subgroup.\n In this randomized, placebo-controlled, double-blind study in hemodialysis patients with hypercholesterolemia (n = 42, mean total cholesterol 243 +/- 33 mg/dl (6.3 +/- 0.8 mmol/l)), the efficacy of 4-weekly increasing doses of atorvastatin (10 - 40 mg daily) was investigated. Lipids and apoproteins were measured in plasma and isolated lipoprotein fractions.\n Mean total cholesterol and low-density lipoprotein cholesterol progressively decreased with increasing doses of atorvastatin (total cholesterol -33%, low-density lipoprotein cholesterol -43% after 12 weeks), while high-density lipoprotein cholesterol remained unchanged. Plasma levels of apoprotein B and apoprotein E were also significantly reduced by atorvastatin 10 mg, while up-titration to 20 and 40 mg daily provided additional benefits by lowering triglycerides and apoprotein C-III. At week 12, the fraction of small dense low-density lipoprotein was significantly reduced from 23% - 18%, and apoprotein B-containing intermediate-density lipoproteins were no longer detectable.\n In conclusion, atorvastatin not only treated hypercholesterolemia but also favorably affected the uremic lipid profile in patients on hemodialysis. Atorvastatin 4-weekly dose escalation up to 40 mg daily was well-tolerated. Further prospective studies are needed to evaluate the impact of this improved lipid profile on morbidity and mortality.", "Effects of pitavastatin and atorvastatin on the lipid profile and lipoprotein subclasses were compared in patients with Type 2 diabetes with dyslipidaemia.\n Patients with Type 2 diabetes with hypercholesterolaemia and/or hypertriglyceridaemia were randomized to receive pitavastatin 2 mg (n = 16) or atorvastatin 10 mg (n = 15) for 6 months, and blood lipid and lipoprotein profiles and cholesterol and triglyceride contents of 20 lipoprotein subclasses, determined by high-performance liquid chromatography, were compared.\n At baseline, cholesterol in VLDL and LDL subclasses were increased equally in two groups of patients with diabetes as compared with normolipidaemic control subjects. As compared with baseline, serum levels of total cholesterol, LDL cholesterol, non-HDL cholesterol, LDL cholesterol:HDL cholesterol ratio and apolipoprotein B were decreased after 1, 3 and 6 months of treatment with atorvastatin and pitavastatin. Serum triglyceride levels were decreased after 1, 3 and 6 months of atorvastatin, but only at 3 months of pitavastatin. Serum HDL cholesterol was increased after 1, 3 and 6 months of pitavastatin, whereas HDL cholesterol was even decreased after 6 months of atorvastatin. Cholesterol levels of most VLDL and LDL subclasses were decreased equally in both groups. However, only pitavastatin increased cholesterol of medium HDL subclass. Serum triglyceride and triglyceride contents in VLDL and LDL subclasses were decreased only by atorvastatin.\n The impact on lipoprotein subclass profiles was different between pitavastatin and atorvastatin. It may be beneficial to determine lipoprotein subclass profile and select the appropriate statin for each profile in patients with diabetes with an additional cardiovascular risk such as low HDL cholesterol or hypertriglyceridaemia.\n © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.", "In a multicenter, open-label trial, 696 Hispanic patients with low-density lipoprotein (LDL) cholesterol levels > or =130 and < or =300 mg/dl and triglyceride levels <400 mg/dl at medium or high risk of coronary heart disease were randomized to receive 10 or 20 mg of rosuvastatin or 10 or 20 mg of atorvastatin for 6 weeks. At week 6, LDL cholesterol was decreased more by 10 mg of rosuvastatin than by 10 mg of atorvastatin (45% vs 36%, p <0.0001) and more by 20 mg of rosuvastatin than by 20 mg of atorvastatin (50% vs 42%, p <0.0001). Significantly greater decreases were also observed with rosuvastatin for total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein-B, and lipid ratios compared with milligram-equivalent doses of atorvastatin. Overall, National Cholesterol Education Program Adult Treatment Program III LDL cholesterol goals were achieved by 78% and 88% of patients who received 10 and 20 mg of rosuvastatin and by 60% and 73% of patients who received 10 and 20 mg of atorvastatin, respectively. Among high-risk patients, the LDL cholesterol goal of <100 mg/dl was achieved by 74% and 91% of patients who received 10 and 20 mg of rosuvastatin and by 52% and 62% who received 10 and 20 mg of atorvastatin, respectively. All treatments were well tolerated, and adverse events were similar in frequency across treatment groups. No cases of myopathy or rhabdomyolysis were observed. In conclusion, treatment with rosuvastatin and atorvastatin produced beneficial lipid changes in this group of Hispanic patients that appear comparable in magnitude to those observed in primarily non-Hispanic white study populations. These benefits were accompanied by a favorable safety profile that suggests no concerns particular to this population.", "Lipid targets can be difficult to attain in familial hypercholesterolaemia. To compare atorvastatin with simvastatin-fenofibrate and simvastatin-cholestyramine therapy, we studied 54 patients with familial hypercholesterolaemia over periods of 2-6 months on each therapeutic regimen. The atorvastatin regimen reduced total cholesterol by 41.2 +/- 11.2%, LDL by 45.6 +/- 15.5%, triglycerides by 33.8 +/- 24.8%, and increased HDL by 2.3 +/- 37.0%. Simvastatin-fenofibrate therapy achieved reductions of 33.9 +/- 8.5% in cholesterol, 42.0 +/- 12.2% in LDL, 34.7 +/- 38.3% for triglycerides, and a 25.4 +/- 55.1% increase in HDL. Simvastatin-cholestyramine gave a reduction of 31.3 +/- 11.8% in cholesterol, 36.0 +/- 14.4% in LDL, 13.7 +/- 36.3% in triglycerides, and a 1.1 +/- 30.3% rise in HDL. The atorvastatin regimen was marginally but not significantly better than simvastatin-fenofibrate in improving the LDL:HDL ratio, LDL:apoB and and apolipoprotein B:A1 ratios. Eleven patients (20.4%) had side-effects: two discontinued atorvastatin due to side-effects; two patients had rashes; six had myalgia and two had diarrhoea. Gastrointestinal side-effects were described in 16 (30.1%) patients on simvastatin-cholestyramine therapy and four cases of myalgia (11.2%) were seen with simvastatin-fenofibrate. In nine patients on atorvastatin (20.4%) a 30% or greater fall in HDL was observed, compared to five patients with resin therapy (9.2%) and two with fibrate therapy (5.5%). There were no significant differences in liver or muscle biochemistry between the regimens, but atorvastatin did raise transaminase and creatine kinase concentrations significantly compared to pre-treatment values (p = 0.001). Atorvastatin significantly improves the lipid profile in most patients compared with other regimens. It has a comparable incidence of side-effects to combination therapy regimens.", "Heterozygous familial hypercholesterolemia (HFH) is a common genetic disorder that confers a significantly increased risk of early coronary artery disease. This study compared atorvastatin and rosuvastatin in reducing low-density lipoprotein (LDL) cholesterol in HFH in a global, 18-week, weighted-randomization, double-blind, parallel-group, forced-titration study. Following a 6-week diet lead-in, 623 patients were randomized to 20 mg/day of atorvastatin (n = 187) or rosuvastatin (n = 436) with forced titration at 6-week intervals to 80 mg/day. The primary end point was percentage change in LDL cholesterol from baseline to week 18. At week 18, rosuvastatin therapy produced a significantly greater reduction in LDL cholesterol than atorvastatin (-57.9% vs -50.4%; p <0.001) and a significantly greater increase in high-density lipoprotein (HDL) cholesterol (12.4% vs 2.9%; p <0.001). Rosuvastatin also produced significantly greater reductions in apolipoprotein-B and all 4 major lipid ratios, as well as a significantly greater increases in apolipoprotein A-I (all p <0.001). More patients with HFH with coronary artery disease achieved the National Cholesterol Education Program Adult Treatment Panel III goal of LDL cholesterol <100 mg/dl (<2.6 mmol/L) on rosuvastatin 40 and 80 mg than atorvastatin 80 mg (17%, 24%, and 4.5%, respectively). High-sensitivity C-reactive protein median values were reduced by 33% to 34% in both the 80-mg rosuvastatin- and atorvastatin-treated groups. Both treatments were well tolerated. Thus, in HFH, rosuvastatin force titrated from 20 to 80 mg/day produced significantly greater reductions than atorvastatin 20 to 80 mg/day in LDL cholesterol and improvements in HDL cholesterol and other lipid parameters, and enabled more patients to achieve LDL cholesterol goals.", "Although previous studies have examined the efficacy of pitavastatin, its tolerability and effects on lipid concentrations have not been compared with those of atorvastatin in a multicenter, randomized study.\n This trial compared the efficacy and tolerability of pitavastatin and atorvastatin in hypercholesterolemic Korean adults.\n This 8-week, multicenter, randomized, open-label, dose-titration study was conducted at 18 clinical centers in Korea between May 2005 and February 2006. After a 4-week dietary lead-in period, patients with hypercholesterolemia were randomized to receive either pitavastatin 2 mg/d or atorvastatin 10 mg/d. Patients who had not reached the low-density lipoprotein cholesterol (LDL-C) goal by week 4 received a double dose of the assigned medication for an additional 4 weeks. Efficacy was evaluated in terms of achievement of the National Cholesterol Education Program Adult Treatment Panel III LDL-C goals and changes from baseline in other lipids and high-sensitivity C-reactive protein (hs-CRP). The tolerability profile was assessed by physical and electro-cardiographic examinations, laboratory tests, and recording adverse reactions at all visits.\n A total of 268 patients were randomized to treatment, and 222 (82.8%) completed the study (149 women, 73 men; mean age, 59 years; mean weight, 63.5 kg). At the end of the study, there was no significant difference between the pitavastatin and atorvastatin groups in the proportion of patients achieving the LDL-C goal (92.7% [102/110] vs 92.0% [103/112], respectively). In addition, there were no significant differences between groups in terms of the percent changes from baseline in LDL-C, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), or hs-CRP. Twenty-six of 136 patients (19.1%) taking pitavastatin reported 35 treatment-emergent adverse reactions; 33 of 132 patients (25.0%) taking atorvastatin reported 39 treatment-emergent adverse reactions. Elevations in creatine kinase were observed in 6 patients (4.4%) in the pitavastatin group and 7 patients (5.3%) in the atorvastatin group. There were no serious adverse drug reactions in either group.\n In these adult Korean patients with hypercholesterolemia, pitavastatin and atorvastatin did not differ significantly in terms of the proportions of patients achieving the LDL-C goal; reductions in LDL-C, total cholesterol, and triglycerides; or increases in HDL-C. Both drugs were well tolerated.", "This study aimed to determine the effect of atorvastatin therapy on plasma lipoprotein (a) [Lp(a)] and biomarkers of inflammation in hypercholesterolaemic patients free of cardiovascular disease.\n In this three-month randomized double-blind placebo-controlled trial, 63 hypercholesterolaemic patients were randomly treated with either placebo or atorvastatin (10 or 40 mg/day) for 12 weeks. Lp(a) and biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6 and -10, and tumour necrosis factor-alpha receptors [TNF-Rs]) were measured at study entry, and at four and 12 weeks of follow-up.\n At the end of the study, patients allocated to atorvastatin (10 or 40 mg/day) presented with significantly lower Lp(a) levels than those taking placebo (10 [1-41]mg/dL versus 6 [1-38]mg/dL [P = 0.02] and 21 [1-138]mg/dL versus 15 [1-103]mg/dL [P = 0.04], respectively]. In multivariate analyses, the relative changes in Lp(a) were independently related to baseline Lp(a) levels and CRP changes. No significant changes in CRP, IL-6 and TNF-Rs were observed. In contrast, IL-10 (pg/mL) increased significantly in patients taking atorvastatin (2.14 [0.49-43]pg/mL versus 4.54 [0.51-37.5]pg/mL; P = 0.01), and was even more increased with the 40-mg dose than with 10mg.\n Our results suggest that 12-week atorvastatin is effective in reducing Lp(a) in dyslipidaemic patients free of CVD. Furthermore, this is also the first evidence that the drug increases IL-10 in a dose-dependent manner.\n Copyright © 2010 Elsevier Masson SAS. All rights reserved.", "Despite the demonstrated benefits of low-density lipoprotein cholesterol (LDL-C) reduction in reducing the risk of coronary heart disease, many patients receiving lipid-lowering therapy fail to achieve LDL-C goals. We compared the effects of rosuvastatin and atorvastatin in reducing LDL-C and achieving LDL-C goals in patients with primary hypercholesterolemia.\n In this 52-week, randomized, double-blind, multicenter trial (4522IL/0026), 412 patients with LDL-C 160 to <250 mg/dL received a 5-mg dose of rosuvastatin (n = 138), a 10-mg dose of rosuvastatin (n = 134), or a 10-mg dose of atorvastatin (n = 140) for 12 weeks; during the following 40 weeks, dosages could be sequentially doubled up to 80 mg if National Cholesterol Education Program Adult Treatment Panel II (ATP-II) LDL-C goals were not achieved. At 12 weeks, 5- and 10-mg doses of rosuvastatin were associated with significantly greater LDL-C reductions than 10-mg doses of atorvastatin (46% and 50% vs 39%, both P <.001). At 12 weeks, both rosuvastatin dosages brought more patients to within ATP-II and European LDL-C goals than atorvastatin (86% and 89% vs 73% and 75%, and 86% vs 55%, respectively). At 52 weeks, compared with atorvastatin, both initial rosuvastatin treatment groups significantly reduced LDL-C (47% and 53% vs 44%, P <.05 and P <.001). Overall, more patients in the initial rosuvastatin 10-mg group achieved their ATP-II LDL-C goal than those in the initial atorvastatin 10-mg group (98% vs 87%), with 82% of patients treated with rosuvastatin achieving their goal at the 10-mg starting dosage without the need for titration, compared with 59% of patients treated with atorvastatin. Both treatments were well tolerated over 52 weeks.\n Compared with atorvastatin, rosuvastatin produced greater reductions in LDL-C, which may offer advantages in LDL-C goal attainment over existing lipid-lowering therapies.", "Preclinical and clinical studies suggest that peroxisome proliferator-activated receptor (PPAR)-δ agonists favorably affect multiple metabolic parameters that are otherwise proatherogenic, many that are not optimally managed with statins alone.\n The aim of this study was to evaluate the effects of MBX-8025 (a novel PPAR-δ agonist) on lipid and other metabolic parameters associated with increased atherosclerotic risk, administered alone and in combination with atorvastatin.\n This was a randomized, double-blind, placebo-controlled, parallel group proof-of-concept study conducted at 30 U.S. research sites.\n This study evaluated 181 overweight men and women with mixed dyslipidemia.\n Subjects were administered once daily placebo, atorvastatin 20 mg, or MBX-8025 at 50 or 100 mg alone or combined with atorvastatin for 8 wk.\n The main efficacy measures included change from baseline in apolipoprotein B-100, lipid levels, high-sensitivity C-reactive protein, and additional metabolic parameters, as well as the effect on the metabolic syndrome and LDL particle size. Results: Compared to placebo, MBX-8025 alone and in combination with atorvastatin significantly (P < 0.05) reduced apolipoprotein B-100 20-38%, LDL 18-43%, triglycerides 26-30%, non-high-density lipoprotein cholesterol 18-41%, free fatty acids 16-28%, and high-sensitivity C-reactive protein 43-72%; it raised high-density lipoprotein cholesterol 1-12% and also reduced the number of patients with the metabolic syndrome and a preponderance of small LDL particles. MBX-8025 was safe and generally well-tolerated. MBX-8025 also reduced liver enzyme levels.\n MBX-8025, a novel PPAR-δ agonist, favorably affected multiple metabolic parameters with and without atorvastatin. A more complete understanding of MBX-8025 requires a larger future study.", "Neutrophil superoxide anion generation was measured during atorvastatin and fluvastatin therapy in patients with coronary heart disease (CHD) risk. The patients were randomly allotted into three groups. The atorvastatin group comprised 17 patients who were administered the drug orally 10 mg a day at bed time. The fluvastatin group consisted of 18 patients on an oral dose of 40 mg once daily at bed time. The control group comprised 12 healthy subjects with no drug administration. Blood samples were collected from cubital vein before and after 6-week therapy with these drugs and once in the control group. Neutrophil superoxide anion generation in whole blood without and with opsonized zymosan (OZ) stimulation was determined using superoxide dismutase from bovine erythrocytes. In the atorvastatin group, statistically significant (P < 0.05) decrease in superoxide anion generation by nonstimulated and OZ-stimulated neutrophils was observed after 6 weeks of therapy. In fluvastatin group, no changes in neutrophil superoxide anion generation were observed after the 6-week treatment period. Our study has shown an additional nonlipid mechanism of atorvastatin used in CHD primary prevention.", "Combination of ezetimibe (EZE) with a statin represents an attractive strategy for cholesterol-lowering treatment, as it inhibits the two main sources of cholesterol: absorption from the intestine (inhibited by EZE) and endogenous biosynthesis (inhibited by statins).\n This multicentre, double-blind, placebo-controlled study randomised a total of 148 men and women with primary hypercholesterolaemia and coronary heart disease (CHD) to receive treatment for 6 weeks with either EZE 10 mg + atorvastatin 10 mg (EZE + ATV; n = 72) or placebo/atorvastatin 10 mg (ATV; n = 76). The primary efficacy variable was the mean percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to study endpoint.\n At 6 weeks, EZE + ATV provided a significantly greater adjusted mean change from baseline in LDL-C compared with ATV monotherapy (-50.5% vs. -36.5%; p < 0.0001), equating to an additional 14.1% reduction (95% CI -17.90, -10.19) in LDL-C. A significantly higher proportion of patients on EZE + ATV achieved the new Joint British Societies (JBS 2) recommended LDL-C goal of < 2 mmol/L (62% vs. 12% with ATV alone; p < 0.0001) and the JBS 2 minimum treatment standard of < 3 mmol/L (93% vs. 79% with ATV alone). Patients receiving EZE + ATV were 12 times more likely to reach LDL-C targets (odds ratio 12.1; 95% CI 5.8, 25.1; p < 0.0001) compared with patients receiving ATV monotherapy. Clinical chemistry profiles and the incidence of adverse events were similar in both groups.\n Adding EZE to ATV monotherapy represents an attractive and well-tolerated treatment option to bring patients at high risk of CHD to the aggressive LDL-C goals recommended by recent treatment guidelines.", "Apolipoprotein (apo) CIII plays an important role in the catabolism of triglyceride-rich lipoproteins as it is a potent inhibitor of lipoprotein lipase (LPL). A low LPL activity has been simultaneously associated with hypertriglyceridemia, low HDL cholesterol and with small LDL particles.\n To compare the effects of a 12-week treatment with micronized fenofibrate (200 mg) versus atorvastatin (10 mg) on apo CIII and lipoprotein-lipid levels including LDL size.\n After a 4-week washout period, dyslipidemic patients were randomized to either micronized fenofibrate (n = 64) or atorvastatin (n = 72).\n Both fenofibrate and atorvastatin significantly decreased apo CIII levels by -0.03 +/- 0.03 versus -0.01 +/- 0.03 g/l respectively, and increased LDL size by 4.9 +/- 3.3 versus 1.8 +/- 2.9 A. Improvements in these parameters were significantly greater with fenofibrate (P < 0.0001). Significant relationships were found between changes in triglycerides and changes in apo CIII (r = 0.81 and r = 0.59, P < 0.0001) as well as between changes in LDL size and changes in apo CIII (r = -0.41 and r = -0.45, P < 0.001), in both fenofibrate and atorvastatin groups. respectively.\n The substantial reduction in apo CIII induced by micronized fenofibrate plays an important role in the greater effect of micronized fenofibrate than atorvastatin on plasma triglycerides and LDL size.", "Combined hyperlipidemia (CHL) is characterized by a concomitant elevation of plasma levels of triglyceride-rich, very low density lipoproteins (VLDLs) and cholesterol-rich, low density lipoproteins (LDLs). The predominance of small, dense LDLs contributes significantly to the premature development of coronary artery disease in patients with this atherogenic dyslipoproteinemia. In the present study, we evaluated the impact of atorvastatin, a newly developed inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, on the cholesteryl ester transfer protein (CETP)-mediated remodeling of apolipoprotein (apo) B-containing lipoprotein subspecies, and more specifically, the particle subpopulations of VLDL and LDL in CHL. In parallel, we evaluated the atorvastatin-induced modulation of the quantitative and qualitative features of atherogenic apo B-containing and cardioprotective apo AI-containing lipoprotein subspecies. Atorvastatin therapy (10 mg/d for a 6-week period) in patients with a lipid phenotype typical of CHL (n=18) induced reductions of 31% (P<0.0001) and 36% (P<0.0001) in plasma total cholesterol and LDL cholesterol, respectively. In addition, atorvastatin significantly reduced VLDL cholesterol, triglycerides, and apo B levels by 43% (P<0.0001), 27% (P=0.0006), and 31% (P<0.0001), respectively. The plasma concentrations of triglyceride-rich lipoproteins (VLDL1, Sf 60 to 400; VLDL2, Sf 20 to 60; and intermediate density lipoproteins, Sf 12 to 20) and of LDL, as determined by chemical analysis, were markedly diminished after drug therapy (-30% and -28%, respectively; P<0.0007). Atorvastatin significantly reduced circulating levels of all major LDL subspecies, ie, light (-28%, P<0.0008), intermediate (-27%, P<0.0008), and dense (-32%, P<0.0008) LDL; moreover, in terms of absolute lipoprotein mass, the reduction in dense LDL levels (mean -62 mg/dL) was preponderant. In addition, the reduction in plasma dense LDL concentration after therapy was significantly correlated with a reduction in plasma VLDL1 levels (r=0.429, P=0.0218). Atorvastatin induced a significant reduction (-7%, P=0.0039) in total CETP-dependent CET activity, which accurately reflects a reduction in plasma CETP mass concentration. Total CETP-mediated CET from high density lipoproteins to apo B-containing lipoproteins was significantly reduced (-26%, P<0.0001) with drug therapy. Furthermore, CETP activity was significantly correlated with the atorvastatin-induced reduction in plasma VLDL1 levels (r=0.456, P=0. 0138). Indeed, atorvastatin significantly and preferentially decreased CET from HDL to the VLDL1 subfraction (-37%, P=0.0064), thereby reducing both the levels (-37%, P=0.0001) and the CE content (-20%, P<0.005) of VLDL1. We interpret our data to indicate that 2 independent but complementary mechanisms may be operative in the atorvastatin-induced reduction of atherogenic LDL levels in CHL: first, a significant degree of normalization of both the circulating levels and the quality of their key precursors, ie, VLDL1, and second, enhanced catabolism of the major LDL particle subclasses (ie, light, intermediate, and dense LDL) due to upregulation of hepatic LDL receptors.", "To assess the lipid-lowering effect of atorvastatin (a new 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitor) on levels of serum triglycerides and other lipoprotein fractions in patients with primary hypertriglyceridemia, determine if atorvastatin causes a redistribution of triglycerides in various lipoprotein fractions, and assess its safety by reporting adverse events and clinical laboratory measurements.\n Randomized double-blind, placebo-controlled, parallel-group, multicenter trial.\n Community- and university-based research centers.\n A total of 56 patients (aged 26 to 74 years) with a mean baseline triglyceride level of 6.80 mmol/L (603.3 mg/dL) and a mean baseline low-density lipoprotein cholesterol (LDL-C) level of 3.07 mmol/L (118.7 mg/dL).\n Cholesterol-lowering diet (National Institutes of Health National Cholesterol Education Program Step I Diet) and either 5 mg, 20 mg, or 80 mg of atorvastatin, or placebo.\n Percent change from baseline in total triglycerides for three dose levels of atorvastatin compared with placebo.\n Mean reductions in total triglycerides between 5 mg, 20 mg, and 80 mg of atorvastatin and placebo after 4 weeks of treatment were -26.5%, -32.4%, -45.8%, and -8.9%, respectively. Mean reductions in LDL-C were -16.7%, -33.2%, -41.4%, and -1.4%, respectively, and very low-density lipoprotein cholesterol (VLDL-C) were -34.3%, -45.9%, -57.7%, and -5.5%, respectively. Similar mean changes in total apolipoprotein B (apo B) (-16.9%, -32.8%, -41.7%, and +1.0%), apo B in LDL (-14.8%, -29.8%, -42.0%, and -3.1%), and apo B in VLDL (-23.8%, -35.8%, -34.4%, and +11.7%) were observed. In addition, comparable mean changes in LDL triglycerides (-22.5%, -30.7%, -39.9%, and +3.9%) and VLDL triglycerides (-28.1%, -34.0%, -47.3%, and -10.8%) were seen.\n In atorvastatin treatment groups, total serum triglyceride levels decreased in a dose-dependent manner, reductions in the 20-mg and 80-mg groups were statistically significant (P < .05) compared with placebo. Atorvastatin did not cause a redistribution of triglycerides but consistently lowered triglycerides in all lipoprotein fractions. Atorvastatin was well tolerated.", "The effect of atorvastatin, at 10 mg or 40 mg for 6 wk, on lipid and lipoprotein metabolism during the postprandial phase in subjects (n = 11) displaying type IIB hyperlipidemia was evaluated. The postprandial increment in area under the curve above baseline concentrations in type IIB subjects was significantly decreased by atorvastatin for plasma triglyceride (A10: -42% and A40: -55%, P < 0.01), chylomicrons (CMs) (A10: -24% and A40: -40%, P < 0.03) and VLDL-1 (A10: -54% and A40: -52%, P < 0.02). Before atorvastatin therapy, postprandial cholesteryl ester (CE) transfer from high-density lipoprotein (HDL) to CMs (2.5-fold; P < 0.005), very low-density lipoprotein (VLDL)-1 (1.8-fold; P < 0.005), VLDL-2 (1.4-fold; P < 0.05), and intermediate-density lipoproteins (1.4-fold; P < 0.05) were significantly increased 4 h postprandially. Following statin treatment, the postprandial transfer of CE from HDL to triglyceride-rich lipoproteins (TRLs) at the 4-h time point was significantly reduced at 10 mg/d (-26%; P < 0.05) and at 40 mg/d (-24%; P < 0.05), compared with that before treatment. Such postprandial increase in CE transferred from HDLs to TRLs arose exclusively from accelerated CE transfer from HDLs to CMs (2.5-fold; P < 0.005). In conclusion, atorvastatin attenuates the abnormal intravascular remodeling of postprandial TRL particles via marked reduction in CE transfer in type IIB hyperlipidemia and diminishes the postprandial formation and accumulation of CMs and VLDL-1.", "Discovery Belux is an open-label, multicentre, randomised, phase IIIb, parallel group study comparing the efficacy of rosuvastatin (RSV) and atorvastatin (ATV) on changes in lipid levels and the achievement of European Atherosclerosis Society (EAS) lipid goals. Patients (> or = 18 years) with primary hypercholesterolaemia, with a low-density lipoprotein (LDL-C) level > 120 mg/dl (on treatment) or > 135 mg/dl (naive subjects), and with a statin indication, were randomised to receive RSV 10 mg/day or ATV 10 mg/day for 12 weeks. Patients not at goal after 12 weeks and receiving ATV 10 were further switched to RSV 10 mg for another 12 weeks. Patients not at goal with RSV 10 mg were further titrated to RSV 20 mg.\n 938 patients were randomised to the two treatment groups. After 12 weeks of treatment, a significantly greater percentage of patients receiving RSV 10 compared with ATV 10 achieved EAS LDL-C target goal (< 115 mg/dl) (85% vs. 67%). LDL-C was reduced by 47% and total cholesterol (TC) by 33% with RSV 10.This was 38% and 27% for ATV 10, respectively. After 24 weeks, an additional 57% of patients initially taking RSV 10 and uncontrolled, reached the target with RSV 20. In the patient group, initially taking ATV 10 and uncontrolled, 65% reached the target with RSV 10 after 24 weeks. Both treatments were well tolerated with a similar incidence of adverse events. In addition, a health economic analysis was performed. As RSV 10 is available at a lower cost in Belgium and as it is more effective, compared to ATV 10, it appeared to be the option of choice from a cost-effectiveness perspective.\n Rosuvastatin 10 mg treatment is significantly more effective than atorvastatin 10 mg at achieving European LDL-C goals, at lowering LDL-C and TC. These results were obtained with a similar safety profile. From a cost-effectiveness perspective RSV 10 is the preferred therapeutic option in comparison with ATV 10. Uptitration of uncontrolled patients to RSV 20 mg and switch from ATV 10 to RSV 10 allowed significantly more patients to reach the LDL-C and TC target goal.", "The transcription factors SREBP1 and SCAP are involved in intracellular cholesterol homeostasis. Polymorphisms of these genes have been associated with variations on serum lipid levels and response to statins that are potent cholesterol-lowering drugs. We evaluated the effects of atorvastatin on SREBF1a and SCAP mRNA expression in peripheral blood mononuclear cells (PBMC) and a possible association with gene polymorphisms and lowering-cholesterol response.\n Fifty-nine hypercholesterolemic patients were treated with atorvastatin (10 mg/day for 4 weeks). Serum lipid profile and mRNA expression in PBMC were assessed before and after the treatment. Gene expression was quantified by real-time PCR using GAPD as endogenous reference and mRNA expression in HepG2 cells as calibrator. SREBF1 -36delG and SCAP A2386G polymorphisms were detected by PCR-RFLP.\n Our results showed that transcription of SREBF1a and SCAP was coordinately regulated by atorvastatin (r=0.595, p<0.001), and that reduction in SCAP transcription was associated with the 2386AA genotype (p=0.019). Individuals who responded to atorvastatin with a downregulation of SCAP had also a lower triglyceride compared to those who responded to atorvastatin with an upregulation of SCAP.\n Atorvastatin has differential effects on SREBF1a and SCAP mRNA expression in PBMC that are associated with baseline transcription levels, triglycerides response to atorvastatin and SCAP A2386G polymorphism.", "The effects of atorvastatin on levels of the CD40 ligand (CD40L or CD154) and P-selectin on platelets were investigated in patients with hypercholesterolemia. The major finding was that short-term atorvastatin treatment (8 weeks) in a group of hypercholesterolemic patients resulted in significant suppression of CD40L and P-selectin expression. Moreover, there was a significant correlation between the magnitude of CD40L downregulation and that of very low-density lipoprotein cholesterol, the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol, and triglycerides. In hypercholesterolemic patients, in addition to its effects on decreasing cholesterol, atorvastatin can intervene in the interaction of CD40-CD40L and the expression of P-selectin on platelets. Thus, interference of CD40-CD40L can be recognized as an integral part of the anti-inflammatory activity of atorvastatin in hypercholesterolemia.", "The purpose of this study was to evaluate the impact of torcetrapib on atherogenic TG-rich lipoprotein subfractions in the postprandial phase in Type IIB hyperlipidemia.\n The quantitative and qualitative features of the postprandial profile of TG-rich lipoproteins were determined at baseline, after treatment for 6 weeks with 10 mg/d atorvastatin, and subsequently with an atorvastatin/torcetrapib combination (10/60 mg/d) in Type IIB patients (n=18). After ingestion of a standardized mixed meal, TG-rich lipoprotein subfractions were evaluated over 8 hours after each experimental period. On a background of atorvastatin, torcetrapib significantly attenuated the incremental postprandial area under the curve (iAUC 0 to 8 hours) for VLDL-1 (-40%), and the AUC 0 to 8 hours for VLDL-2 (-53%), with minor effect on chylomicron iAUC (-24%); concomitantly, the CE/TG ratio in both VLDL-1 and VLDL-2 was significantly reduced (-27% to -42%). Such reduction was attributable to torcetrapib-mediated attenuation of postprandial CE transfer to Chylomicrons (-17%) and VLDL-1 (-33%). Marked reduction in postprandial VLDL-1 levels was associated with apoE enrichment.\n On a background of atorvastatin, torcetrapib attenuated the quantitative and qualitative features of the atherogenic postprandial profile of chylomicrons, VLDL-1 and VLDL-2. Such changes reflect the sum of torcetrapib-mediated effects on TG-rich lipoprotein production, intravascular remodeling, and catabolism.", "Although recent lipid-lowering therapies are effective in reducing low density lipoprotein-cholesterol (LDL-C) levels, many patients treated with lipid-lowering agents do not achieve target LDL-C levels, especially in very high risk patients. The aim of this study is to compare the effect of ezetimibe/simvastatin 10/20 mg and atorvastatin 20 mg on achieving a target LDL-C goal in very high risk patients.\n A total of 74 patients with very high risk were enrolled in the study. Very high risk patients were defined as patients that displayed established cardiovascular disease with multiple major risk factors, poorly controlled risk factors, multiple risk factors of the metabolic syndrome and acute coronary syndromes. Patients were randomized into two groups: ezetimibe/simvastatin 10/20 mg (n=36) and atorvastatin 20 mg (n=38). Follow-up lipid profile was obtained 6 weeks later. A target goal of LDL-C was defined as less than 70 mg/dL at follow-up.\n Baseline clinical and laboratory data were similar between the two groups. Achieving a target LDL-C goal was observed in 41.7% of Group 1 and 44.7% of Group 2 at 6 weeks (p=0.82). Changes in other lipid profiles were not significantly different but the tolerability of the two groups was similar.\n Ezetimibe/simvastatin 10/20 mg and atorvastatin 20 mg showed similar effects in achieving target LDL-C levels in patients with very high risk.", "Increased sympathetic activity might be related to pathogenesis of hypertension as well as to end organ damage. Animal studies suggest that statins decrease sympathetic activity and increase baroreceptor reflex sensitivity (BRS).\n To examine whether atorvastatin decreases muscle sympathetic nerve activity (MSNA) and BRS in hypercholesterolaemic and hypertensive patients.\n Ten patients with essential hypertension and untreated hypercholesterolaemia (aged 43 +/- 12 years) and eight healthy subjects (aged 37 +/- 7 years) were enrolled in the study. In both groups the recordings of microneurography, ECG, blood pressure and BRS were performed twice, before and after 8 weeks during which the patients (but not controls) were treated with atorvastatin.\n Compared with controls, the patients had higher MSNA values (36.0 +/- 6.6 vs. 29.8 +/- 3.7 bursts/minute), mean BP levels (145.1 +/- 10 vs. 124.1 +/- 11.1 mmHg) and total cholesterol concentration (252.6 +/- 22.6 vs. 179.8 +/- 20.7 mg/dl) baseline values. Statin therapy resulted in a decrease of total cholesterol (252.6 +/- 22.0 vs. 173.8 +/- 26.2 mg/dl, p < 0.05) and MSNA (36.0 +/- 6.6 vs. 28.6 +/- 4.8 bursts/min, p < 0.05), whereas BRS values were increased (12.6 +/- 5.6 vs. 18.1 +/- 5.9 ms/mmHg, p < 0.05). Post-treatment BRS was inversely related to post-treatment MSNA (r = -0.73, p < 0.05). In the controls there were no changes in MSNA (29.8 +/- 3.7 vs. 28.9 +/- 2.9 bursts/min), BRS (11.9 +/- 5.0 vs. 13.1 +/- 4.8 ms/mmHg), total cholesterol, BP and heart rate between the first and the second measurement.\n Atorvastatin reduces MSNA and increases BRS in hypertensive and hypercholesterolaemic patients. Decrease in sympathetic activity may be the result of improvement of baroreceptor function by atorvastatin.", "The aim of the present study was to see whether a moderate dose of omega-3 fatty acids (FA) potentiates the beneficial effects of statins on the high risk for coronary heart disease (CHD) in patients with combined hyperlipemia.\n In the present double-blind parallel study, 42 patients with combined hyperlipemia with serum triglycerides 2-15 mmol/L-1 and serum total cholesterol > 5.3 mmol/L-1 at the end of a three-month dietary run-in period were treated with 10 mg/d atorvastatin for 10 or more weeks. During the last 5 weeks they were randomized into two groups that received either 1.68 g/d omega-3 FA as ethylesters of eicosapentaenoic (45%) and docosahexaenoic acids (39%), or placebo (corn oil). As expected, atorvastatin significantly reduced serum total LDL-cholesterol (LDL-C), triglycerides and apolipoproteins B, E, CII and CIII, whereas HDL-cholesterol (HDL-C) was increased. Addition of omega-3 FA further increased HDL-C (p < 0.03), and reduced systolic blood pressure (< 0.03), while the small dense LDL-particles (LDL III) (p < 0.05) and postprandial hypertriglyceridemia (p < 0.01) were reduced compared with the baseline, though there were no significant differences to the placebo group. This may be related to the large individual variation in these parameters and the small number of patients. No significant effects on basic or postheparin activities of lipoprotein lipase or hepatic lipase were observed after atorvastatin with or without addition of omega-3 FA.\n This study indicates that addition of a low dose of omega-3 FA may further improve the risk profile for CHD in patients with combined hyperlipemia treated with atorvastatin. The effect is related to reduction of postprandial hyperlipemia and redistribution of LDL subfractions.", "Endothelial function is impaired in healthy subjects at risk of type 2 diabetes mellitus (DM). We investigated whether endothelial dysfunction can be normalized by statin therapy in this potentially predisposed population. Flow-mediated dilation (FMD) was measured in 56 first-degree relatives (FDRs) (normotensive, normal glucose tolerance) and 20 age-, sex-, and BMI-matched controls with no family history of DM. Other measurements included insulin resistance index using the homeostasis model of insulin resistance (HOMA(IR)), plasma lipids, and markers of inflammation. The FDRs were then randomized and treated with atorvastatin (80 mg) or placebo daily in a 4-week double-blind, placebo-controlled trial. The FDRs had significantly impaired FMD (4.4 +/- 8.1% vs. 13.0 +/- 4.2%; P < 0.001), higher HOMA(IR) (1.72 +/- 1.45 vs. 1.25 +/- 0.43; P = 0.002), and elevated levels of plasma markers of inflammation-highly sensitive C-reactive protein (hsCRP) (2.6 +/- 3.8 mg/L vs. 0.7 +/- 1.0 mg/L; P = 0.06), interleukin (IL)-6 (0.07 +/- 0.13 ng/mL vs. 0.03 +/- 0.01 ng/mL; P < 0.001), and soluble intercellular adhesion molecule (sICAM) (267.7 +/- 30.7 ng/mL vs. 238.2 +/- 20.4 ng/mL; P < 0.001). FMD improved in the atorvastatin-treated subjects when compared with the placebo-treated subjects (atorvastatin, from 3.7 +/- 8.5% to 9.8 +/- 7.3%; placebo, from 3.9 +/- 5.6% to 4.7 +/- 4.2%; P = 0.001). There were also reductions in the levels of IL-6 (0.08 +/- 0.02 ng/mL vs. 0.04 +/- 0.01 ng/mL; P < 0.001) and hsCRP (3.0 +/- 3.9 mg/L vs. 1.0 +/- 1.3 mg/L; P = 0.006). Our study suggests that treatment with atorvastatin may improve endothelial function and decrease levels of inflammatory markers in FDRs of type 2 DM patients.", "Fasting plasma mevalonic acid (MVA), an indicator of in vivo cholesterol synthesis, was measured in 35 patients with familial hypercholesterolaemia (FH) of whom 7 were treated with pravastatin 10-40 mg/day, 7 with simvastatin 10-40 mg/day and 21 with atorvastatin 80 mg/day. Reductions in low density lipoprotein (LDL) cholesterol and MVA on maximal dose therapy differed significantly between the three drugs: 34.7%, 42.9% and 54.0% (P = 0.0001), and 31.6%, 48.9% and 58.8% (P = 0.004), respectively. Patients on atorvastatin were subdivided according to whether their reduction in LDL cholesterol on treatment was above or below the mean percentage change for the whole group. Basal values of LDL cholesterol did not differ significantly, but above average responders had a significantly higher mean pre-treatment level of MVA (6.2 +/- 0.60 vs. 4.3 +/- 0.61 ng/ml, P < 0.05) than below average responders. When all three drug groups were pooled above average responders showed a significantly greater absolute decrease in MVA on treatment than below average responders (3.85 +/- 0.48 vs. 2.33 +/- 0.40 ng/ml, P < 0.05). However, there was no significant correlation between the magnitude of the decreases in LDL cholesterol and MVA. These findings suggest that FH patients who responded well to statins had a higher basal level of plasma MVA, i.e. a higher rate of cholesterol synthesis, which was more susceptible to pharmacological inhibition. The more marked cholesterol lowering effect of atorvastatin 80 mg/day presumably reflects, at least in part, its ability to inhibit HMG-CoA reductase to a greater extent than maximal recommended doses of pravastatin and simvastatin of 40 mg/day.", "Hyperlipidemia is commonly observed in patients with type 2 diabetes and is an independent risk factor for cardiovascular disease. The authors tested the effect of atorvastatin (10 mg/d) on 110 hyperlipidemic type 2 diabetes patients with low-density lipoprotein cholesterol (LDL-C) levels exceeding 130 mg/d. The primary efficacy end point was the percentage change in LDL-C and high-density lipoprotein cholesterol (HDL-C), and secondary efficacy included the percentage change in apolipoproteins at weeks 6, 12, and 24. The tertiary goal was percentage change in free radical scavenger enzymes and oxidative stress. LDL-C was reduced by 25%, 39.3%, and 49.2%. A similar trend was observed in total cholesterol, triglyceride, non-HDL-C, and apolipoprotein (apo) B-100. HDL-C was raised by 3.2%, 6%, and 8.2%. A similar trend was seen in apo A-1. Copper zinc-superoxide dismutase and glutathione were raised significantly (P < .001); however, changes in glutathione-S-transferase and glutathione peroxidase activities were nonsignificant. Malondialdehyde was decreased significantly (P < .001). Atorvastatin improves the lipoprotein profile and oxidative status in patients with type 2 diabetes.", "To compare the efficacy and safety of the recommended usual starting and next highest doses of ezetimibe/ simvastatin and atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia.\n This double-blind, multicenter study (June 22 to December 7, 2005) consisted of adult patients randomized to the recommended usual starting (ezetimibe/simvastatin, 10/20 mg/d, vs atorvastatin, 10 or 20 mg/d) or next highest (ezetimibe/simvastatin, 10/40 mg/d, vs atorvastatin, 40 mg/d) doses. Efficacy end points included percent changes from baseline in low-density lipoprotein cholesterol (LDL-C) levels (primary) and proportion of patients attaining LDL-C levels less than 70 mg/dL (secondary).\n A total of 1229 patients participated in the study. Significantly greater mean reductions were found in LDL-C levels with ezetimibe/simvastatin, 10/20 mg/d (-53.6%; 95% confidence interval [CI], -55.4% to -51.8%), than with atorvastatin, 10 mg/d (-38.3%; 95% CI, -40.1% to -36.5%; P < .001) or 20 mg/d (-44.6%; 95% CI, -46.4% to -42.8%; P < .001), and with ezetimibe/simvastatin, 10/40 mg/d (-57.6%; 95% CI, -59.4% to -55.8%), vs atorvastatin, 40 mg/d (-50.9%; 95% CI, -52.7% to -49.1%; P < .001). Ezetimibe/simvastatin was also superior to atorvastatin in attainment of LDL-C levels less than 70 mg/dL (P < .001 for all dose comparisons). Significantly better improvements with ezetimibe/simvastatin than with atorvastatin (P < or = .001) were observed for total cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol. Ezetimibe/ simvastatin, 10/20 mg/d, reduced high-sensitivity C-reactive protein and triglyceride levels significantly more than atorvastatin, 10 mg/d (P = .02), with comparable reductions at other doses. Incidences of clinical adverse events, including serious drug-related and prespecified gastrointestinal-, gallbladder-, and hepatitis-related allergic reactions or rash events, and laboratory adverse events, including repeated elevation of hepatic transaminases or creatine kinase levels, were similar for both treatments.\n Ezetimibe/simvastatin provided additional lipid-modifying benefits over atorvastatin monotherapy at the recommended usual starting and next highest doses in patients with type 2 diabetes. Both treatments were generally well tolerated.", "Atorvastatin is a powerful new synthetic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor currently in clinical use. Its effects on plasma levels of factor VII were examined in 30 hyperlipidemic patients. After 12 weeks of atorvastatin treatment, factor VII activity (FVIIc) and factor VII antigen (FVIIag) levels had decreased by 13% (p < 0.0001) and 12% (p < 0.0001), respectively. The decreased concentrations of serum triglycerides correlated with decreases in FVIIc levels (r = 0.54, p = 0.0023) and FVIIag levels (r = 0.59, p = 0.0006) at 12 weeks of treatment with atorvastatin. No significant changes were seen in activated factor VII (FVIIa) levels. Plasma concentrations of fibrinogen were slightly, but not significantly, increased at 12 weeks. No significant changes were seen in plasminogen activator inhibitor-1 levels. The effects of atorvastatin on FVII may contribute to a decreased thrombotic potential, resulting in fewer thromboembolic events, including a reduction in coronary heart disease.", "Statins have been shown to have pleiotropic effects extending beyond their ability to lower cholesterol.\n Seventeen patients with heterozygous familial hypercholesterolaemia participated in a single-blind placebo controlled study. The patients underwent three treatment regimens: placebo (4 weeks), atorvastatin 10 mg day(-1) (4 weeks) and atorvastatin 40 mg day(-1) (12 weeks). Following each treatment period, serum lipids and plasma mevalonic acid were measured, mononuclear leukocytes were isolated and total RNA was prepared. The content of mRNA for IL-12p35 and IL-10 was assayed, blinded, by real-time quantitative polymerase chain reactions.\n Treatment of the subjects with atorvastatin decreased the abundance of IL-12p35 mRNA in mononuclear cells, but did not alter that of IL-10, so that the ratio of the IL-12p35 to IL-10 mRNA content was significantly reduced (P < 0.0026). The IL-12p35/IL-10 ratio correlated significantly with plasma mevalonic acid concentrations but not with serum LDL concentrations.\n This study provides evidence that atorvastatin exerts an immunomodulatory effect in vivo, characterized by a decrease in the ratio of IL-12 mRNA to IL-10 mRNA in leukocytes. The immunomodulatory effect of statins, in addition to their cholesterol-lowering properties, may contribute to the rapid cardiovascular benefit observed during treatment with statins and reduced the rate of rejection in patients with solid organ transplantation.", "Familial combined hyperlipidemia (FCHL), the most common inherited disorder of lipid metabolism, is associated with an increased risk of atherosclerosis that is not fully explained by the metabolic disturbances of these patients. Oxidative damage to lipid components accumulating in the plasma of FCHL patients might contribute to explaining this lack of evidence. Cholesterol is one of the preferential targets of oxidation in LDL and this may contribute to setting a proatherogenetic phenotype in FCHL. We investigated plasma oxysterols (7-ketocholesterol and 7beta-hydroxycholesterol) and alpha-tocopherol as in vivo hallmarks of lipid-related oxidative stress. Oxidative stress hallmarks were measured in 45 FCHL patients and 54 sex- and age-matched healthy controls; in FCHL patients, oxidative stress and lipid profile parameters were also assessed in response to lipid-lowering drugs in a 24-week randomized, open-label trial with atorvastatin or fenofibrate. FCHL patients showed markedly increased levels of oxysterols (p < 0.001) and reduced alpha-tocopherol/total lipids (p < 0.001) compared to controls. These differences were independent of the presence of clinical atherosclerosis and persisted after correction for hyperlipidemia. Atorvastatin and fenofibrate significantly improved the lipid profile and caused a comparable decrease in plasma oxysterols, with the normalization of 7-ketocholesterol and a significant reduction of 7beta-hydroxycholesterol (p < 0.001). These drugs also decreased the ratio of alpha-tocopherol/total lipids by more than 30% (p < 0.001). In conclusion, FCHL patients showed increased hallmarks of cholesterol oxidation and decreased levels of alpha-tocopherol/total lipids. Atorvastatin and fenofibrate displayed comparable efficiency in decreasing oxysterols, but they further decreased lipid-corrected alpha-tocopherol levels in plasma. More research work is needed to understand the clinical meaning of these findings, which may help to understand the role of oxidative stress in FCHL and lipid-lowering therapy.", "Statins and fibrates have different effects on lipid abnormalities of familial combined hyperlipidemia (FCHL); thus, the selection of the first-line drug is troublesome. We evaluated to what extent monotherapy with a potent statin is more effective than fibrate in reaching the recommended lipid targets in FCHL. Fifty-six patients were randomized to receive optimal dosage of atorvastatin (n = 27) or 200 mg/d micronized fenofibrate (n = 29) for 24 weeks. To reach the optimal dosage, atorvastatin was up-titrated at each follow-up visit if low-density lipoprotein (LDL) cholesterol >130 mg/dL (>100 mg/dL in patients with coronary or cerebrovascular disease). The effects of fenofibrate and atorvastatin on lipoprotein fractions as well as on plasma levels of endothelin-1 (ET-1) and adrenomedullin (AM) were also evaluated. At end of trial, a greater proportion of patients on atorvastatin (average dosage, 20.8 mg/d) reached lipid targets in comparison with those on fenofibrate (64% vs 32.1%, P = .02). Atorvastatin was significantly more effective in reducing total cholesterol, LDL cholesterol, apolipoprotein B, and non-high-density lipoprotein (HDL) cholesterol. Conversely, triglycerides decreased and HDL increased more during fenofibrate. Nevertheless, atorvastatin produced a marked reduction in very low-density lipoprotein and very low-density lipoprotein remnants. Atorvastatin lowered all LDL subtypes, although fenofibrate appeared to be more effective on denser LDL. Compared with 43 normolipemic controls, FCHL patients presented increased baseline plasma levels of ET-1 (P = .007) but not of AM. Fenofibrate, but not atorvastatin, significantly lowered ET-1 levels by 16.7% (P < .05). Neither drug significantly affected plasma concentrations of AM. In summary, although fenofibrate showed superiority in raising HDL and reducing ET-1, atorvastatin was more effective in reaching lipid targets in FCHL so that it can be proposed as the first-line option in the management of this atherogenic hyperlipidemia.", "Previous studies have suggested that statins exert beneficial effects beyond their favorable lipid lowering effect. Particularly, the modification of thrombus formation and degradation, alteration in inflammatory response, plaque stabilization and improved endothelial function are thought to be responsible for additional reduction of morbidity and mortality due to cardiovascular events. To date, however, it is still unclear whether these effects are elicited by all statins.\n We set out to compare in a controlled, randomized, double-blind study design the effects of almost equieffective cholesterol lowering doses of three chemically and pharmacokinetically different statins (atorvastatin, simvastatin, pravastatin) on hemostatic and inflammatory markers in 99 hypercholesterolemic patients. At entry and 3 months after onset of statin therapy plasma cholesterol and von Willebrand factor antigen (vWf-Ag), fibrinogen, d-dimer, prothrombin fragment 1+2 (F1.2) and C-reactive protein (CRP) were measured. The effect on plasma values of F1.2, vWf-Ag, d-dimer and CRP was not significantly different between the three treatment groups. The effect of simvastatin on fibrinogen (p = 0.005) was more pronounced than the effects of atorvastatin (p = 0.48 n.s.) and pravastatin (p = 0.15 n.s.). Plasma levels of F1.2 and vWf-Ag (when data of all statins were pooled) were significantly reduced by 7% and 10% versus baseline, respectively. No significant reduction was observed for d-dimer (p = 0.26) and CRP (p = 0.5). Total plasma cholesterol levels decreased significantly (p < 0.0001 in all groups) between 22% and 29% compared to baseline.\n The present study shows similar short-term (3 months) effects of atorvastatin, simvastatin and pravastatin on selected hemostatic and inflammatory parameters in plasma in patients with hypercholesterolemia. Thus, chemical and pharmacological differences between statins appear to exert no major influence on these parameters.", "This study compared the relative efficacy of a once-daily niacin extended-release (ER)/lovastatin fixed-dose combination with standard doses of atorvastatin or simvastatin, with a special emphasis on relative starting doses. Subjects (n = 315) with elevated low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol blood levels (defined as LDL cholesterol blood levels > or =160 mg/dl without coronary artery disease, or > or =130 mg/dl if coronary artery disease was present, and HDL cholesterol <45 mg/dl in men and <50 mg/dl in women) were randomized to atorvastatin, simvastatin, or niacin ER/lovastatin for 16 weeks. The primary efficacy variables were the mean percent change in LDL cholesterol and HDL cholesterol levels from baseline. After 8 weeks, the starting dose niacin ER/lovastatin 1,000/40 mg and the 10-mg starting dose atorvastatin both lowered mean LDL cholesterol by 38%. After 12 weeks, niacin ER/lovastatin 1,000/40 mg lowered LDL cholesterol by 42% versus 34% with the 20-mg starting dose of simvastatin (p <0.001). Niacin ER/lovastatin increased HDL cholesterol significantly more than atorvastatin or simvastatin at all compared doses (p <0.001). Niacin ER/lovastatin also provided significant improvements in triglycerides, lipoprotein(a), apolipoprotein A-1, apolipoprotein B, and HDL subfractions. A total of 6% of study subjects receiving niacin ER/lovastatin withdrew because of flushing. No significant differences were seen among study groups in discontinuance due to elevated liver enzymes. No drug-induced myopathy was observed. Niacin ER/lovastatin was comparable to atorvastatin 10 mg and more effective than simvastatin 20 mg in reducing LDL cholesterol, was more effective in increasing HDL cholesterol than either atorvastatin or simvastatin, and provided greater global improvements in non-HDL cholesterol, triglycerides, and lipoprotein(a).", "nan", "Formation of nitric oxide-derived oxidants may serve as a mechanism linking inflammation to development of atherosclerosis. Nitrotyrosine, a specific marker for protein modification by nitric oxide-derived oxidants, is enriched in human atherosclerotic lesions and low-density lipoprotein (LDL) recovered from human atheroma.\n To determine whether systemic levels of nitrotyrosine are associated with the prevalence of coronary artery disease (CAD) and are modulated by hydroxymethylglutaryl coenzyme-A reductase inhibitor (statin) therapy.Design, Setting, and\n A case-control and interventional study at 2 urban tertiary-care referral centers; recruitment for each was from June 1, 2001, until January 1, 2002. For the case-control study, 100 case-patients with established CAD and 108 patients with no clinically evident CAD were recruited consecutively. In the interventional study, participants aged 21 years or older with hypercholesterolemia (LDL cholesterol > or =130 mg/dL [> or =3.5 mmol/L]) underwent nutrition and exercise counseling. Those whose levels did not decrease with 6 to 8 weeks were enrolled in the study (n = 35). For 12 weeks, they received 10 mg/d of oral atorvastatin therapy.\n In the case-control study, the association between systemic levels of protein-bound nitrotyrosine, CAD risk, and presence of CAD. In the interventional study, the change in nitrotyrosine, lipoprotein, and C-reactive protein (CRP) levels.\n Nitrotyrosine levels were significantly higher among patients with CAD (median 9.1 micromol/mol [interquartile range, 4.8-13.8 micromol/mol] tyrosine vs 5.2 micromol/mol [interquartile range, 2.2-8.4 micromol/mol]; P<.001). Patients in the upper quartile of nitrotyrosine (29%; P<.001) had a higher odds of CAD compared with those in the lowest quartile (unadjusted odds ratio, 6.1; 95% confidence interval, 2.6-14.0; P<.001). In multivariate models adjusting for Framingham Global Risk Score and CRP, upper quartiles of nitrotyrosine remained associated with CAD (odds ratio, 4.4; 95% confidence interval, 1.8-10.6; P<.001). Statin therapy reduced nitrotyrosine levels significantly (25%; P<.02) with a magnitude similar to reductions in total cholesterol levels (25%; P<.001) and LDL particle number (29%; P<.001) yet were independent of alterations in lipoproteins and inflammatory markers like CRP.\n The findings from this preliminary study indicate that nitrotyrosine levels are associated with the presence of CAD and appear to be modulated by statin therapy. These results suggest a potential role for nitric oxide-derived oxidants as inflammatory mediators in CAD and may have implications for atherosclerosis risk assessment and monitoring of anti-inflammatory actions of statins.", "The studies results of statin influence on hemostasis are various. The aim of our study was to evaluate the effects of simvastatin and atorvastatin on hemostatic parameters, such as activity of factor X, antithrombin III, fibrinogen concentration and Lp(a). 72 patients (pts) aged 40-65 were involved in the study; 49 of them suffered from hyperlipidemia II (hlp II) with the initial concentration of total cholesterol (TC) >200 mg/dL, cholesterol LDL (LDL-C) >145 mg/dL, triglycerides (TG) <400 mg/dL. The control group consisted of 20 healthy persons. The pts with hlp II who underwent 4 weeks long lipid lowering diet were randomized into two groups: I--27 pts treated with simvastatin (20 mg/d), II--22 pts treated with atorvastatin (10 mg/d). The active statin therapy lasted 8 weeks. The activity of factor X and antithrombin III (AT III) was estimated by amidolytic methods, fibrinogen concentration (Fb) by the Clauss method, Lp(a)-immunoenzymatic method. The mean values of factor X activity and Fb serum concentration were higher in pts with hip II than in the control group, the AT III activity was lower. The Lp(a) concentration didn't differ between groups. Statin treatment was associated with significant reduction of factor X activity. Both simvastatin and atorvastatin markedly increased AT III (87%, 98%) in comparison to the initial values. No changes of Lp(a) concentration were observed during statin therapy. Atorvastatin therapy significantly increased the Fb concentration (12.3%). Simvastatin treatment didn't influence Fb concentration.", "Few data are available on the effects of high dose statin therapy on lipoprotein subfractions in type 2 diabetes. In a double blind randomised placebo-controlled trial we have studied the effects of 80 mg atorvastatin over 8 weeks on LDL, VLDL and HDL subfractions in 40 overweight type 2 diabetes patients. VLDL and LDL subfractions were prepared by density gradient ultracentrifugation. Triglycerides, cholesterol, total protein and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. Atorvastatin 80 mg produced significant falls in LDL subfractions (LDL(1) 66.2 mg/dl:36.6 mg/dl, LDL(2) 118:56.6 mg/dl, LDL(3) 36.9:19.9 mg/dl all P < 0.01 relative to placebo) and VLDL subfractions (VLDL(1) 55:22.1 mg/dl, VLDL(2) 40.1:19.1 mg/dl, VLDL(3) 52.6:30 mg/dl all P < 0.01 relative to placebo). There was no change in the proportion of LDL present as LDL(3). There was a reduction in the proportion of VLDL as VLDL(1) and a reciprocal increase in the proportion as VLDL(3). Changes in VLDL subfractions were associated with changes in lipid composition, particularly a reduction in cholesterol ester and a reduction in the cholesterol ester/triglyceride ratio. Effects on HDL subfractions were largely neutral. High dose atorvastatin produces favourable effects on lipoprotein subfractions in type 2 diabetes which may enhance antiatherogenic potential.", "Policosanol, commonly derived from purified sugar cane wax, has been reported to exert lipid-lowering effects. Policosanol is available in the United States as a nutritional supplement despite no US research clinical experience. This trial was designed to rigorously establish the lipid-lowering efficacy of policosanol as monotherapy and its potential additive and possibly synergistic effects when added to statin therapy.\n A randomized, parallel, double-blind, double-dummy, placebo-controlled design was used. Patients with low-density lipoprotein cholesterol (LDL-C) levels from 140 to 189 mg/dL were assigned into 1 of 4 groups to receive policosanol 20 mg, atorvastatin 10 mg, combination therapy, or placebo for 12 weeks.\n A total of 99 patients were examined. Baseline characteristics were similar among all treatment groups. Policosanol (20 mg/d for 12 weeks) did not significantly change plasma total cholesterol, LDL-C, high-density lipoprotein cholesterol, or triglyceride levels when compared with baseline values or with values of placebo-treated patients. Atorvastatin (10 mg/d for 12 weeks) reduced total cholesterol by 27% and LDL-C by 35%. Addition of policosanol to atorvastatin failed to produce any further reduction in lipid levels above that of atorvastatin alone. Policosanol was safe and did not affect liver enzyme or creatinine phosphokinase levels.\n Policosanol did not reduce LDL-C or total cholesterol levels either alone or in combination with atorvastatin. This observation supports the need for systematic evaluation of available products containing policosanol to determine their clinical lipid-lowering efficacy under rigorous experimental conditions. We propose that policosanol should be added to the list of nutritional supplements lacking scientific validity to support their use.", "This study compares the cholesterol-lowering efficacy of atorvastatin and simvastatin in attainment of the National Cholesterol Education Program (NCEP) guidelines LDL-cholesterol (LDL-C) goal in patients with heterozygous familial hypercholesterolemia (HFH). The association of atorvastatin with significant changes of blood fibrinogen and other coagulative variables was also compared with that of simvastatin.\n In a 24-week study, 26 HFH patients (16 men, 10 women, mean age 55.1 +/- 11.3) were randomly assigned to receive atorvastatin or simvastatin. The initial daily dose of 10 mg was progressively raised to 20, 40 and 80 mg in patients who had not reached the NCEP LDL-C goal. Significant reductions of total and LDL-C (p < 0.001), triglycerides (p < 0.005) and apoB100 (p < 0.001) were observed in both groups. Atorvastatin caused greater reductions in total cholesterol (-42% vs -30%) (p < 0.001) and LDL-C (-50% vs -37%) (p < 0.01). Three patients treated with Atorvastatin (23%) and none of those treated with simvastatin reached the NCEP LDL-C goal at the end of the study. No significant departures from the fibrinogen and coagulative variable baselines were observed.\n Atorvastatin has greater cholesterol-lowering efficacy than simvastatin in HFH.", "Information about the effects of HMG-CoA reductase inhibitor (statin) treatment on lipoprotein subclasses has been severely limited. Nuclear magnetic resonance (NMR) spectrometry has emerged as a new methodology to quantify lipoprotein subclass concentrations. In the present study, we attempted to evaluate the hypolipidemic effects of atorvastatin utilizing this method.\n Twenty-six patients were administered with atorvastain 10 mg daily for 4 weeks. Lipoprotein subclasses were measured by nuclear magnetic resonance (NMR) spectroscopy. Inflammation markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1), were also determined.\n Additional to a marked reduction of LDL-C (-43%), atorvastatin treatment significantly decreased TG, RLP-C, apoC-II, apoC-III, and apoE by 27%, 49%, 25%, 15%, and 28%, respectively. NMR analysis revealed marked reductions of all LDL subclasses, resulting in a significant reduction of LDL particle number as well as an increase in LDL particle size. Further, some VLDL were decreased and HDL particle size was increased by atorvastatin. Among inflammation markers, MDA-LDL and IL-6 were marginally to significantly decreased.\n In addition to a strong LDL-C lowering function, atorvastatin exerts beneficial effects on TG-rich lipoproteins and inflammation in hypercholesterolemic patients.", "Lowering of serum cholesterol levels by pharmacologic intervention with statins reduces the incidence of cardiovascular events in subjects with and without atherosclerotic manifestations. In an 8-week, randomized, double-blind study we compared the efficacy and safety of the new compound atorvastatin for reducing LDL-cholesterol (LDL-C) with placebo in an Asian patient cohort. Patients with LDL-C between 160 mg/dl and 250 mg/dl were randomly assigned to treatment with 10 mg atorvastatin or placebo once daily for 8 weeks. At the end of weeks 4 and 8 of the randomized phase, the serum concentrations of lipid parameters as well as safety parameters were determined. Fifty-four patients (32 males and 22 females) were enrolled. Twenty-six patients were assigned to the treatment group. The primary end-point, LDL-C, was reduced by 40% and 42% after 4 and 8 weeks of treatment in the atorvastatin treated patients (p<0.001). The reductions in total cholesterol and triglycerides were up to 31% and 23%, respectively. The HDL-C levels increased up to 11% (p=0.043). There were no significant adverse events. Transient increases in CPK levels (10 times) without myalgia were identified in 1 patient. Atorvastatin, 10 mg/day produced significant reductions in LDL-C, total cholesterol and triglycerides and an elevation of HDL-C levels when used as an adjunct to diet in hyperlipidemic patients. The majority of the clinical effects could be attained by week 4. The overall safety profile of atorvastatin was similar to that of placebo. Atorvastatin was considered to be well tolerated in this patient cohort.", "Hyperandrogenaemia in polycystic ovary syndrome (PCOS) represents a composite of raised serum concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS). In patients with PCOS, testosterone and androstenedione are primarily derived from the ovaries and DHEAS is a metabolite predominantly from the adrenals. It has been shown that atorvastatin reduces testosterone concentrations in patients with PCOS. The objective was to study the effect of atorvastatin on serum androstenedione and DHEAS concentrations in patients with PCOS.\n A randomized, double-blind, placebo-controlled study was performed. Forty medication-naive patients with PCOs were randomized to either atorvastatin 20mg daily or placebo for three months. Subsequently, a three-month extension study for all patients was undertaken with metformin 1500 mg daily. The main outcome measures were change in androstenedione and DHEAS concentrations.\n The mean (SD) baseline androstenedione (5.7 [0.8] versus 5.6 [1.3] nmol/L; P = 0.69) and DHEAS (7.1 [1.0] versus 7.2 [1.2] μmol/L; P = 0.72) concentrations were comparable between two groups. There was a significant reduction of androstenedione (5.7 [0.8] versus 4.7 [0.7] nmol/L; P = 0.03) and DHEAS (7.1 [1.0] versus 6.0 [0.9] μmol/L; P = 0.02) with three months of atorvastatin while there were no significant changes with placebo. Three months' treatment with metformin maintained the reduction of androstenedione and DHEAS concentrations with atorvastatin compared with baseline. There were no changes in either DHEAS or androstenedione concentrations in the initial placebo group after 12 weeks of metformin.\n Twelve weeks of atorvastatin significantly reduced both DHEAS and androstenedione contributing to the total reduction of androgen concentrations and indicating that the reduction of the hyperandrogenaemia could be partly due to the action of atorvastatin at both the ovary and the adrenal gland in PCOS.", "To compare the effects of simvastatin and atorvastatin on hemostatic parameters.\n Sixty-one patients with primary hypercholesterolemia without coronary heart disease were treated with atorvastatin 10-20 mg/d or simvastatin 10-20 mg/d. At baseline, 4, 12, and 24 weeks, lipid levels such as low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triglycerides (TGs), and hemostatic parameters such as platelet counts, partial thromboplastin time (PTT) prothrombin time (PT), and fibrinogen levels were measured.\n At 12 weeks, the doses of the statins were increased to 20 mg/d in 10 of 35 (28.5%) patients treated with atorvastatin and 18 of 26 (69.2%) patients treated with simvastatin when the target level of LDL-C (130 mg/dL) was not reached. Mean doses were atorvastatin 12.8 mg/d and simvastatin 16.9 mg/d. After 24 weeks, 5 patients (14.3%) in the atorvastatin group and 4 patients (15.3%) in the simvastatin group had not reached the goal. In patients with diabetes, target level (LDL-C <100 mg/dL) was not reached in 35.7% of patients in the atorvastatin group and 44.4% of patients in the simvastatin group. Both simvastatin and atorvastatin were effective in lowering TC and LDL-C levels (p < 0.001). Atorvastatin lowered TGs significantly (p < 0.01). Neither atorvastatin nor simvastatin significantly reduced VLDL-C levels. HDL-C levels increased with atorvastatin, but there was no significant difference between the 2 groups. Platelet counts decreased with both statins nonsignificantly. Moreover, fibrinogen levels decreased with simvastatin and atorvastatin, but these reductions were significant only for simvastatin (p < 0.05). We detected prolongation of the PT with both drugs (p < 0.05); however, prolongation of the PTT was significant only with simvastatin (p < 0.001). Effectiveness of both statins on lipid and hemostatic parameters was dose related. Adverse effects were seen in 5 patients (14.2%) treated with atorvastatin and 3 patients (11.5%) treated with simvastatin. Elevations in serum transaminase levels >3 times the upper limit of normal and in creatine phosphokinase >5 times the upper limit of normal were not observed in any group.\n Atorvastatin was more effective than simvastatin on lipid parameters, although statistically insignificantly, while simvastatin produced more significant changes than atorvastatin on hemostatic parameters. The mean dose of simvastatin was greater than that of atorvastatin. Both statins had increased effects on lipid and hemostatic parameters when doses were increased. Atorvastatin and simvastatin were well tolerated. Different effects of statins on lipid levels and on coagulation parameters should be considered in patients with hypercholesterolemia and tendency to coagulation, especially in preventing thrombotic events. Further studies in larger trials are needed to confirm these observations.", "To investigate the impact of Vitamin E on lipids and peroxidation during statin treatment.\n T1DM patients with high cholesterol received Atorvastatin 20mg with either placebo (group AP, n = 11) or d-alpha-tocopherol 750 IU (group AE, n = 11) daily. They were monitored for blood biochemistry, low-density lipoprotein (LDL) subfractions and lipid peroxidation at inclusion and after 3 and 6 months.\n Serum cholesterol and triglycerides decreased to the same extent (29 and 21% respectively) in both groups. Serum tocopherol decreased by 18% in AP and increased by 50% in AE (P < 0.0001, between-group comparison by repeated measures ANOVA) but relative to lipids it increased by 15% in AP and by 100% in AE. Copper-induced production of thiobarbituric reactive substances in the LDL + VLDL fraction increased by 18% in AP and did not change in AE (P = 0.02). The lagtime for the production of fluorescent products was prolonged by 13 min only in group AE (P = 0.028). Plasma malondialdehyde decreased by 35% in both groups (P = 0.002) but not when adjusted for lipids.\n In T1DM Vitamin E supplements do not affect the lowering of lipids and plasma malondialdehyde achieved by Atorvastatin. They reverse the increase of in vitro peroxidation caused by Atorvastatin but do not achieve the decreases observed in patients not receiving lipid-lowering drugs. These results indicate that the antioxidant effect of Vitamin E is attenuated when given in conjunction with this statin.\n Copyright 2004 Elsevier Ireland Ltd", "The reduction in plasma LDL-C concentrations with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy has been reported to reduce cardiovascular risk and mortality in individuals with or without preexisting coronary artery disease and elevated LDL-C concentrations. Atorvastatin is a statin used for lowering LDL-C concentrations. A generic formulation of atorvastatin is being developed in Korea. This study was undertaken for the purposes of marketing the generic formulation.\n This study was designed to compare the efficacy and tolerability of a generic formulation of atorvastatin 20 mg/d versus a branded formulation at the same dosage in hypercholesterolemic Korean adults at high risk for cardiovascular events.\n This 8-week, multicenter, randomized, double-blind, double-dummy study was conducted at 10 clinical centers in Korea between September 2008 and May 2009. Male and female patients aged 20 to 85 years at high risk for cardiovascular events (defined as an elevated LDL-C concentration [≥100 mg/dL]) were enrolled. Eligible patients were randomly assigned to receive generic or branded atorvastatin 20 mg once daily for 8 weeks. The primary end point was the percentage change from baseline to 8 weeks in LDL-C concentration. Secondary end points were the percentage changes from baseline in total cholesterol (TC), triglycerides (TG), HDL-C, apolipoprotein (apo) A1 and B, and high-sensitivity C-reactive protein concentrations; small, dense LDL (sdLDL) fraction; and tolerability. Tolerability was assessed using physical examination, laboratory testing, and by recording adverse events (AEs) at each visit. An additional secondary end point was the proportion of patients who achieved an LDL-C goal of <100 mg/dL.\n A total of 244 patients were randomized to treatment, and 33 patients were withdrawn from the study (9 patients did not receive the study medication, 11 patients due to AEs, and 13 patients due to withdrawal of consent). A total of 211 patients completed the study (50.7% male; 100% Asian; mean [SD] age, 61.7 [9.2] years) (106 patients in the group that received Accepted for publication October 5, 2010. the generic formulation and 105 patients in the group that received the branded formulation). LDL-C concentrations were reduced from the baseline by 44% and 46% after 8 weeks of treatment with the generic and branded formulations, respectively (P = NS). The percentage changes from baseline to study end in HDL-C, TC, TG, apo A1, apo B, and hsCRP concentrations and sdLDL fraction the proportions of patients who achieved the LDL-C goal between the 2 groups did not reach statistical significance. The most commonly reported events were hepatobiliary laboratory abnormality (1.7%), general somatic discomfort (1.7%), and epigastric pain (0.8%) in the group that received the generic formulation, and myalgia (1.7%), epigastric pain (0.9%), and elevation of creatinine phosphokinase (0.9%) in the group that received the branded formulation. No serious AEs were reported in either group.\n After 8 weeks of treatment, the differences in the LDL-C-lowering effects between the generic and branded formulations of atorvastatin 20 mg/d did not reach statistical significance in these Korean patients at high risk for cardiovascular events. Both formulations were generally well tolerated.\n Copyright © 2010 Excerpta Medica Inc. All rights reserved.", "Combination therapy of rosiglitazone and atorvastatin has been shown to have beneficial effects on glycemic control and lipid profiles in patients with type 2 diabetes mellitus. This study investigated the effects of the combination of rosiglitazone and atorvastatin on vascular inflammation by studying their effects on levels of biomarkers in patients with type 2 diabetes mellitus. Thirty patients with type 2 diabetes mellitus and hyperlipidemia were enrolled to receive rosiglitazone monotherapy at 4 mg/day for 3 months and then atorvastatin at 10 mg/day was added for 3 more months as combined therapy. Inflammatory biomarkers, including high-sensitivity C-reactive protein (hs-CRP), matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand (sCD40L), and adiponectin, and lipid profiles were measured at the time of initiation, after rosiglitazone monotherapy and after combination therapy with rosiglitazone and atorvastatin. With treatment of rosiglitazone at 4 mg/day monotherapy for 3 months, hs-CRP levels decreased significantly by 26% (p <0.05) and adiponectin levels increased significantly by 192% (p <0.05), but no significant changes in levels of MMP-9 and sCD40L were demonstrated. After combination therapy, hs-CRP levels further significantly decreased by another 23% (p <0.05) and adiponectin further increased by another 124%. In addition, serum levels of MMP-9, sCD40L, total cholesterol, and low-density lipoprotein cholesterol decreased significantly compared with baseline levels. In conclusion, combination therapy with rosiglitazone and atorvastatin not only significantly improved lipid profiles but also decreased levels of vascular biomarkers, such as hs-CRP, MMP-9, and sCD40L, and increased serum adiponectin levels in patients with type 2 diabetes mellitus.", "Statin therapy can reduce the biosynthesis of both cholesterol and coenzyme Q10 by blocking the common upstream mevalonate pathway. Coenzyme Q10 depletion has been speculated to play a potential role in statin-related adverse events, and withdrawal of statin is the choice in patients developing myotoxicity or liver toxicity. However, the effect of statin withdrawal on circulating levels of coenzyme Q10 remains unknown. Twenty-six patients with hypercholesterolemia received atorvastatin at 10 mg/day for 3 months. Serum lipid profiles and coenzyme Q10 were assessed before and immediately after 3 months and were also measured 2 and 3 days after the last day on the statin. After 3 months' atorvastatin therapy, serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and coenzyme Q10 (0.43 +/- 0.23 to 0.16 +/- 0.10 microg/mL) were all significantly reduced (all p<0.001). On day 2 after the last atorvastatin, the coenzyme Q10 level was significantly elevated (0.37 +/- 0.16 microg/mL) and maintained the same levels on day 3 (0.39 +/- 0.18 microg/mL) compared with those on month 3 (both p< 0.001), while TC and LDL-C did not significantly change within the same 3 days. These results suggest that statin inhibition of coenzyme Q10 synthesis is less strict than inhibition of cholesterol biosynthesis.", "Beyond lipid lowering, statins have pleiotropic effects with favourable benefits against atherogenesis. Withdrawal of statin therapy has been demonstrated to abrogate vascular protective activity and even increase the incidence of thrombotic vascular events. The purpose of this study is to investigate the serial changes of soluble CD40 ligand (sCD40L) and two adipocytokines, adiponectin and resistin, after short-term atorvastatin therapy and withdrawal in patients with hypercholesterolaemia.\n Thirty-two patients with hypercholesterolaemia received atorvastatin 10 mg/day for 3 months. Serum lipid profiles, and levels of sCD40L, adiponectin and resistin, were assessed before and immediately after 3 months' statin therapy. Serum levels of sCD40L and adiponectin were also measured on the 3 consecutive days after statin withdrawal. After 3 months' statin therapy, levels of sCD40L (1.93 +/- 1.13 vs. 1.30 +/- 0.97 ng/mL), total cholesterol and low-density lipoprotein cholesterol (LDL-C) were all reduced significantly (p < 0.05). However, sCD40L level tended to increase towards baseline on the first and second days after statin withdrawal, but was not significantly elevated until the third day after withdrawal (1.89 +/- 1.28 vs. 1.30 +/- 0.97 ng/mL, p < 0.05). Total cholesterol and LDL-C levels did not increase during the 3 days of statin withdrawal. No significant changes of adiponectin and resistin levels were shown after statin therapy.\n These results indicate that the effect of statin on sCD40L level was abrogated after therapy withdrawal, and was independent of serum cholesterol level. Statin therapy did not significantly alter levels of adiponectin and resistin.", "We have investigated the effect of atorvastatin on the endothelial function of patients with diabetes and subjects at risk for type 2 diabetes in a 12-wk, prospective, randomized, placebo-controlled, double-blind clinical trial. The flow- mediated dilation (FMD; endothelium dependent) and nitroglycerin-induced dilation (endothelium independent) in the brachial artery and the vascular reactivity at the forearm skin were measured. FMD improved in the atorvastatin-treated, at-risk subjects [median (25-75 percentile), 7.2% (2.9-9.6%) at exit visit vs. 6.6% (2.9-9.5%) at baseline; P < 0.05]. A similar improvement of FMD was found in atorvastatin-treated diabetic patients [median (25-75 percentile), 5.6 (3.9-7.9) at exit visit vs. 4.2 (3.2-7.2) at baseline; P = 0.07]. No changes were observed in nitroglycerin-induced dilation and the microcirculation reactivity measurements in either group. In the at-risk group, there was a decrease in the C-reactive protein [median (25-75 percentile), 0.12 mg/dl (0.07-0.27 mg/dl) at exit visit vs. 0.24 mg/dl (0.07-0.35 mg/dl) at baseline; P < 0.05] and TNF alpha [median (25-75 percentile), 2.6 pg/ml (1.8-4.1 pg/ml) at exit visit vs. 4.4 pg/ml (3.6-6.0 pg/ml) at baseline; P < 0.05] in the atorvastatin-treated patients, whereas in the diabetes group, a decrease in endothelin-1 (mean +/- SD, 0.97 +/- 0.29 pg/ml at exit visit vs. 1.19 +/- 0.42 pg/ml at baseline; P < 0.05) and plasminogen activator inhibitor-1 [median (25-75 percentile), 18 ng/ml (9-24 ng/ml) at exit visit vs. 27 ng/ml (7-41 ng/ml) at baseline; P < 0.05] were observed. We conclude that atorvastatin improves endothelial function and decreases levels of markers of endothelial activation and inflammation.", "This study evaluated the effect of correction of serum cholesterol levels on erectile function and sildenafil treatment in patients with erectile dysfunction who have only hypercholesterolaemia as a risk factor for erectile dysfunction.\n Twenty-five patients with a single risk factor (hypercholesterolaemia, serum cholesterol > 200 mg/dl) for erectile dysfunction were included in the study. The patients were recommended to take sildenafil (minimum two 100 mg tablets/week) 1 h before sexual intercourse for 4 weeks. After 1 month washout period, the patients received a single dose of atorvastatin 10 mg/day for 1 month. Similarly, after a 1 month washout period, atorvastatin 10 mg/day and sildenafil (minimum two 100 mg tablets/week) were administered for 1 month as combination therapy. Erectile function was evaluated before and after all treatment regimens using the International Index of Erectile Function (IIEF).\n Following each treatment modality mean IIEF scores were significantly higher than baseline IIEF scores (p < 0.01). The IIEF score after sildenafil treatment was significantly higher than in the atorvastatin treatment group (p < 0.01); and the IIEF score after combined treatment was significantly higher than in the sildenafil and atorvastatin treatment groups.\n Correction of serum cholesterol levels with atorvastatin could improve erectile function in patients who have only hypercholesterolaemia as a risk factor for erectile dysfunction. Furthermore, atorvastatin could improve sildenafil's effects on erectile function in hypercholesterolaemic patients with erectile dysfunction.", "We conducted an open-label study to test the effects of atorvastatin on serum lipids, lipoprotein(a) [Lp(a)] and plasma fibrinogen levels. A total of 90 dyslipidaemic, non-smoking patients (45 patients with primary hypercholesterolaemia and 45 patients with primary mixed hyperlipidaemia) aged 48 +/- 11 years were studied. The patients were treated with 20 mg of atorvastatin for 24 weeks, in a single nocturnal dose. At baseline and every eight weeks, the fasting lipid profile, together with serum Lp(a) and plasma fibrinogen levels (Clauss method), were measured. Atorvastatin was highly effective in normalising the serum lipid profile. No significant change in median serum Lp(a) levels was observed in the whole group of patients (0.14 g/l before, vs. 0.16 g/l after, treatment) as well as in patients with raised (> 0.30 g/l) baseline levels (n = 32). A small non-significant increase of plasma fibrinogen was found (3.04 g/l vs. 3.14 g/l) after 24 weeks of atorvastatin administration. The effects of atorvastatin on both these variables did not differ in patients with hypercholesterolaemia or mixed hyperlipidaemia. In conclusion, our findings suggest that the effect of atorvastatin on plasma fibrinogen levels in dyslipidaemic patients without evident vascular disease is not clinically relevant. Furthermore, any rise in fibrinogen levels that may occur is likely to be transient in nature. Further studies are necessary to clarify this issue. There was no evidence that atorvastatin influences serum Lp(a) levels.", "Type 2 diabetes increases the risk for cardiovascular disease, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) reduce cardiovascular events in these patients. The benefits of statin therapy cannot be explained only by the lipid-lowering effect. The aim of this study was to test the effect of atorvastatin therapy on CD36 scavenger receptor expression, nuclear factor-kappaB (NFkappaB) levels and markers of inflammation (C-reactive protein, CRP, Tumor Necrosis Factor-alpha, TNF-alpha) in circulating monocytes from diabetic patients.\n Twenty-two type 2 diabetic patients were treated for 8 weeks with atorvastatin (20 mg/day). At baseline and after treatment a blood sample was collected for measurement of glucose, lipid profile (total cholesterol, HDL, LDL cholesterol, triglycerides), glycated hemoglobin (HbA1c), CRP and for isolation of monocytes.\n Atorvastatin decreased total (p<0.0001) and LDL (p<0.01), and incresased HDL choles-terol (p<0.02). CD36 surface protein expression (anti-CD36 fluorescein isothiocyanate-FITC) was reduced in circulating monocytes after atorvastatin therapy (p<0.02) while immunoblot analysis showed reduced nuclear and increased cytoplasm NFkappaB levels (p<0.05). Finally, TNFalpha production in lipopolysaccharide-activated monocytes from patients treated with atorvastatin was reduced (p<0.05).\n These results suggest that atorvastatin therapy, beside lowering serum cholesterol levels, could exert anti-atherogenic and anti-inflammatory effects in type 2 diabetic patients.", "There is interindividual variation in low-density lipoprotein cholesterol (LDLc) lowering by statins and limited study into the genetic associations of the dose dependant LDLc lowering by statins.\n Five hundred nine patients with hyperlipidemia were randomly assigned atorvastatin 10 mg, simvastatin 20 mg, or pravastatin 10 mg (low-dose phase) followed by 80 mg, 80 mg, and 40 mg (high-dose phase), respectively. Thirty-one genes in statin, cholesterol, and lipoprotein metabolism were sequenced and 489 single nucleotide polymorphisms with minor allele frequencies >2% were tested for associations with percentage LDLc lowering at low doses using multivariable adjusted general linear regression. Significant associations from the analysis at low dose were then repeated at high-dose statins. At low doses, only 1 single nucleotide polymorphism met our experiment-wide significance level, ABCA1 rs12003906. Twenty-six subjects carried the minor allele of rs12003906, which was associated with an attenuated LDLc reduction (LDLc reduction in carriers versus noncarriers -24.1+/-2.6% versus -32.2+/-1.5%; P=0.0001). In addition, we replicated the association with the APOE epsilon3 allele and a reduced LDLc reduction. At high doses, carriers of the minor allele of ABCA1 rs12003906 and the APOE epsilon3 allele improved their LDLc reduction but continued to have a diminished LDLc reduction compared with noncarriers (-30.5+/-4.0% versus -42.0+/-2.4%; P=0.005) and (-38.5+/-1.9% versus -45.3+/-2.8%; P=0.009), respectively.\n An intronic single nucleotide polymorphism in ABCA1 and the APOE epsilon3 allele are associated with reduced LDLc lowering by statins and identify individuals who may be resistant to maximal LDLc lowering by statins.", "The AVALON study was a randomized, multicenter trial to assess the efficacy and safety of coadministered amlodipine and atorvastatin in patients with hypertension and dyslipidemia. Phase one was an 8-week, double-blind, double-dummy, placebo-controlled period whereby patients received amlodipine 5 mg, atorvastatin 10 mg, amlodipine 5 mg and atorvastatin 10 mg, or placebo. Thereafter, all patients received single-blind amlodipine 5 mg and atorvastatin 10 mg for 8-weeks, followed by 12 weeks of open-label treatment where doses could be titrated to improve low-density lipoprotein cholesterol and blood pressure control. A total of 847 patients entered the double-blind phase. At Week 8, 45% of the patients receiving amlodipine 5 mg and atorvastatin 10 mg reached both their blood pressure and low-density lipoprotein cholesterol goals, compared with 8.3% with amlodipine (p < 0.001), 28.6% with atorvastatin (p < 0.001), and 3.5% with placebo. At 28 weeks, 67.1% of patients coadministered amlodipine and atorvastatin (mean doses, 7.6 mg and 28.4 mg, respectively) achieved both targets. Framingham estimated 10-year risk of coronary heart disease declined from baseline levels of 15.1% to 6.9% at Week 28. Following coadministered treatment, the adverse events reported were similar to either agent alone. Concomitant administration of amlodipine and atorvastatin is an effective and well tolerated treatment for coexisting hypertension and dyslipidemia.", "Oxidative stress in diabetes increases lipid peroxidation, which stimulates the development of atherosclerosis.\n We investigated in a 3-month placebo-controlled study with 19 normocholesterolemic type 2 diabetic patients whether treatment with 10-mg atorvastatin influenced antioxidants and reduced LDL oxidizability, assessed by in vitro production of conjugated dienes after copper-induced LDL oxidation.\n The lag phase, as a measure of the resistance of LDL to oxidation, did not change (62.8+/-8.2 respectively 59.6+/-9.7 min, p=n.s.), while conjugated dienes decreased (512+/-74 respectively 487+/-50 nmol, p=0.012). Plasma alpha-tocopherol and ubiquinol levels decreased, while their ratios to LDL cholesterol remained stable.\n Atorvastatin favourably influences some parameters of LDL oxidation. Whether this effect is clinically relevant remains to be determined.", "Previous studies have shown conflicting results on low-density lipoprotein cholesterol (LDL-C) reduction for comparable doses of pitavastatin and atorvastatin.\n To compare the efficacy of pitavastatin 1 mg once daily with that of atorvastatin 10 mg once daily on lipoprotein change, safety, and cost per percent LDL-C reduction.\n An 8-week, randomized, open-label, parallel trial was conducted in patients with hypercholesterolemia. One hundred patients were equally randomized to receive pitavastatin 1 mg once daily or atorvastatin 10 mg once daily; 98 completed the study. Outcomes were assessed at baseline and at the end of the study.\n Pitavastatin lowered LDL-C levels from baseline by 37% compared with 46% in the atorvastatin group (p < 0.001). The reduction of total cholesterol (TC) levels from baseline was significantly different between the pitavastatin (28%) and atorvastatin (32%) groups (p = 0.005). There was no significant difference in the percentage of changes in triglyceride and high-density lipoprotein cholesterol levels between groups. The percentage of patients who achieved LDL-C goals according to National Cholesterol Education Program-Adult Treatment Panel III guidelines was not significantly different between the pitavastatin (74%) and atorvastatin (84%) groups (p = 0.220). In addition, both regimens were well tolerated, with no patient developing an elevation of more than 3 times the upper normal limit of alanine aminotransferase or 10 times that of creatine kinase. The monthly cost per percent LDL-C reduction in the pitavastatin group ($0.77) was about 50% lower than the cost in the atorvastatin ($1.56) group.\n Although pitavastatin 1 mg daily was not as effective at lowering LDL-C and TC levels as atorvastatin 10 mg daily, the number of patients achieving their LDL-C goals with pitavastatin was comparable with the number using atorvastatin. Pitavastatin 1 mg once daily may be an alternative regimen with cost-saving benefits but without a significant decrease in therapeutic benefit or increase in adverse events in patients with hypercholesterolemia.", "To find the clinical variables associated with atorvastatin's effects on bone metabolism markers, 35 patients with heterozygous familial hypercholesterolemia were treated with atorvastatin for 24 weeks, and the levels of bone formation markers (bone-specific alkaline phosphatase and osteocalcin) and resorption marker (urine collagen type-1 cross-linked N-telopeptide) were determined. Pretreatment vitamin D levels showed significant and positive associations with changes in 2 bone formation markers. The serial changes in 3 markers were favorable-increased bone formation markers and unchanged bone resorption marker-but the changes occurred only in patients with pretreatment vitamin D levels >50 pg/ml.", "Patients at high risk of cardiovascular disease frequently fail to reach recommended low-density lipoprotein cholesterol (LDL-C) goals, partly because statin doses are not titrated to optimal effect. The ECLIPSE study was designed to compare the efficacy and safety of force-titrated treatment with rosuvastatin (10-40 mg) with that of atorvastatin (10-80 mg) in high-risk patients with hypercholesterolemia.\n In this 24-week, open-label, randomized, multinational, parallel-group study, 1,036 patients were randomized to rosuvastatin (n = 522) or atorvastatin (n = 514).\n At all time points, a significantly greater percentage of patients on rosuvastatin treatment achieved the NCEP ATP III LDL-C goal of <100 mg/dl (2.5 mmol/l), the 2003 European LDL-C target of <2.5 or 3.0 mmol/l (100 or 115 mg/dl) and the LDL-C goal of <70 mg/dl (1.8 mmol/l), a goal suggested for very high-risk patients (p < 0.001 for all). Rosuvastatin also achieved significantly greater improvements in components of the atherogenic lipid profile versus atorvastatin. Both treatments were well tolerated.\n Rosuvastatin titrated across its recommended dose range provides a more favorable effect on lipoprotein variables than atorvastatin, enabling more high-risk patients to achieve recommended LDL-C goals.\n Copyright 2008 S. Karger AG, Basel.", "There is controversy about the effects of statins on plasma adiponectin, and the impact of percutaneous coronary intervention (PCI) on plasma adiponectin level is still unknown. We investigated the impact of Atorvastatin on plasma adiponectin levels in coronary artery disease (CAD) patients with stable angina and normal lipid profiles after PCI.\n Sixty CAD patients with stable angina and normal lipid profiles scheduled for PCI, and not on statins, were randomly assigned to either no treatment (control group) or the Atorvastatin treatment (Atorvastatin group). Atorvastatin administration was started immediately after PCI. Blood samples were obtained immediately after PCI and again 3 and 6 mo later. Fasting plasma adiponectin concentrations were measured using a radioimmunoassay kit.\n After PCI, there were statistically significant decreases in adiponectin levels in the Atorvastatin group at 3 and 6 mo (8.66 +/- 0.69 versus 6.87 +/- 0.55 and 7.12 +/- 0.71 microg/mL at 0, 3, and 6 mo, respectively), despite the anti-inflammation and lipid-lowering effects of Atorvastatin. There were no statistically significant changes in adiponectin levels in the control group. There was significant positive association between baseline plasma adiponectin and high-density lipoprotein (HDL) levels. Changes of adiponectin level were not associated with the changes of high-sensitivity C-reactive protein (hs-CRP) and lipid profiles in the Atorvastatin group.\n Our study confirmed the benefits of Atorvastatin on anti-inflammation and anti-atherosclerosis, but we also found that Atorvastatin had a negative effect on the adiponectin system. The anti-inflammatory, anti-atherogenic effects of Atorvastatin are not affected by decreased adiponectin levels.", "National Cholesterol Education Program Adult Treatment Panel III guidelines for patients at a high risk of coronary heart disease set a low-density lipoprotein cholesterol (LDL-C) target of < 100 mg/dL. This target can be difficult to attain with diet and current therapy.\n In a 16-week multinational trial, 1993 high-risk patients were randomized to rosuvastatin 20 mg, atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, or simvastatin 40 mg for 8 weeks. Patients either remained on starting treatment or switched to lower or milligram-equivalent doses of rosuvastatin for 8 more weeks.\n At 16 weeks, more patients achieved their LDL-C target by switching to rosuvastatin 10 mg than staying on atorvastatin 10 mg (66% vs 42%, P < .001) or simvastatin 20 mg (73% vs 32%, P < .001). Changing to rosuvastatin 20 mg brought more patients to their LDL-C target than staying on atorvastatin 20 mg (79% vs 64%, P < .001) or simvastatin 40 mg (84% vs 56%, P < .001). More very high risk patients achieved an LDL-C target of < 70 mg/dL when changed to rosuvastatin from atorvastatin or simvastatin (within-arm comparisons P < .01). More hypertriglyceridemic patients (triglycerides > or = 200 mg/dL) met LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B targets by changing to rosuvastatin. Switching to rosuvastatin produced greater reductions in LDL-C, total cholesterol, non-HDL-C, apolipoprotein B, and lipid ratios. All treatments were well tolerated, with no differences among treatment groups in skeletal muscle, hepatic, or renal toxicity.\n Rosuvastatin 10 or 20 mg is an effective and safe therapeutic option for high-risk patients to achieve their lipid and apolipoprotein targets.", "To determine the effect of atorvastatin on postprandial lipaemia in overweight or obese women with the apoprotein (apo) E3/E3 genotype.\n Double-blind randomised, placebo-controlled 8-week single-centre study.\n Twenty-two healthy women, homozygous for apo E3 with a BMI ranging from 27.6 to 41.1 kg/m2 and normal or moderately elevated fasting triglycerides (53-184 mg/dl).\n After a 4-week isocaloric single-blind, placebo lead-in period, subjects were randomly assigned to receive either placebo (n = 7) or atorvastatin 20 mg once daily in the evening (n = 15) for 4 weeks.\n Atorvastatin significantly reduces fasting total cholesterol, LDL-cholesterol and postprandial triglycerides in obese women, homozygous for apo E3 with normal or near-normal fasting triglyceride levels. No significant effect on fasting triglycerides was observed.\n Atorvastatin decreases postprandial hyperlipidaemia, an independent cardiovascular risk factor, in normolipidaemic obese women. This effect of atorvastatin may, therefore, represent a cardioprotective mechanism.", "As statins may contribute to plaque stabilisation, it is important to evaluate whether these drugs may modify arterial stiffness. In 23 patients, aged 32-70 years, with hypertension and hypercholesterolaemia, a double-blind randomised study vs placebo was performed to evaluate whether atorvastatin was able to modify aortic stiffness, measured from aortic pulse wave velocity (PWV), after a 12-week treatment. The results revealed that atorvastatin did not change blood pressure, significantly lowered (P<0.003; <0.002) plasma total and LDL cholesterol, and increased aortic PWV by +8% (vs -2% under placebo) (P<or=0.05). The percentage changes in plasma total and LDL cholesterol and in PWV were significantly and negatively correlated, independent of blood pressure level. The finding of increased aortic PWV after 12-week statin treatment agrees with studies in monkeys, indicating that, at the early phase of hypolipidaemic diet but not later, aortic PWV increases transiently as a consequence of the significant reduction of lipid vascular content. In conclusion, the present results support the possibility that statins might contribute to a change in arterial stiffness independent of blood pressure level, and suggest that long-term studies in humans are needed to evaluate the contribution of arterial elasticity to statin-induced vascular remodelling.", "To compare the efficacy of the newest cholesterol-lowering drug, rosuvastatin (RSV) with atorvastatin (ATV) in subjects with type 2 diabetes.\n A 24-week, open-label, randomized, parallel-group, phase IIIb, multicentre study.\n Diabetes outpatient clinics of 26 hospitals in The Netherlands.\n A total of 263 patients with type 2 diabetes treated with oral agents or insulin, age (mean +/- SD) 60 +/- 10 years, body mass index (BMI) 31.4 +/- 6.1 kg m(-2), 46% males.\n After a 6-week dietary lead-in period, patients were randomized to RSV (n = 131) or ATV (n = 132) treatment in a dose escalation scheme (RSV: 10, 20 and 40 mg or ATV: 20, 40 and 80 mg for 6 weeks each sequentially).\n Primary outcome was the change in apolipoprotein B (apoB) and apoB/apolipoprotein A1 (apoA1) ratio, which has been suggested a better predictor for cardiovascular events than total (TC) or low-density lipoprotein cholesterol (LDL-C). Secondary outcomes were the changes in other lipid parameters.\n Baseline LDL-C in the RSV and ATV groups was 4.23 +/- 0.98 mmol L(-1) and 4.43 +/-0.99 mmol L(-1), whilst apoB/apoA1 was 0.86 +/-0.22 and 0.92 +/- 0.35, respectively. A greater reduction in apoB/apoA1 was seen with RSV (-34.9%, -39.2% and -40.5%) than with ATV (-32.4%, -34.7% and -35.8%, P < 0.05 at weeks 12 and 18). Significantly greater reductions in LDL-C were also seen with RSV (-45.9%, -50.6% and -53.6%) than with ATV (-41.3%, -45.6% and -47.8%, all P < 0.05). The American Diabetes Association (ADA) LDL-C goal of < 2.6 mmol L(-1) was reached by 82%, 84% and 92% of patients with RSV and 74%, 79% and 81% with ATV. Triglyceride reductions ranged from 16 to 24% and were not different between treatments. Both treatments were well-tolerated: nine patients in the RSV and 11 in the ATV group withdrew from treatment because of adverse events after randomization.\n In subjects with type 2 diabetes, greater improvements of apoB/apoA1 and across the lipid profile were observed with RSV compared with ATV.", "Atorvastatin is a potent hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor that decreases low-density lipoprotein (LDL) cholesterol and triglyceride concentrations, but little is known about its effects on LDL subtype distribution in different types of hyperlipoproteinemia. Thus, we evaluated the influence of atorvastatin (10 mg/d, 4 weeks) on lipid concentrations and LDL subtype distribution in patients with hypercholesterolemia (n = 9; LDL cholesterol, 227 +/- 30 mg/dL; triglycerides, 137 +/- 56 mg/dL), patients with type 2 diabetes and dyslipoproteinemia (n = 11; LDL cholesterol, 163 +/- 34 mg/dL; triglycerides, 260 +/- 147 mg/dL), and controls (n = 10; LDL cholesterol, 116 +/- 20 mg/dL; triglycerides, 130 +/- 47 mg/dL). Cholesterol concentration was determined in 7 LDL subfractions isolated by density gradient ultracentrifugation before and during atorvastatin treatment. Atorvastatin decreased LDL cholesterol (-36%, -28%, and -41%, all P <.01) and triglyceride (-4%, NS; -2%, NS; -24%, P <.05) concentrations but had little effect on high-density lipoprotein (HDL) cholesterol (-1%, NS; +10%, P <.05; +6%, NS) in hypercholesterolemic, diabetic, and control subjects, respectively. In all 3 groups, a significant reduction in cholesterol in each LDL subfraction was observed. Large-buoyant (LDL-1, LDL-2) and intermediate-dense (LDL-3, LDL-4) LDL were reduced more than small-dense (LDL-5 through LDL-7) LDL in hypercholesterolemic (-45%, -35%, and -32%, P <.05) and control subjects (-48%, -44%, and -25%, P <.05), but in diabetic patients cholesterol reduction was uniform in all LDL subtypes (-32%, -27%, and -29%, P =.45). Thus, atorvastatin decreases cholesterol concentration in all LDL subfractions in hypercholesterolemic, diabetic, and control subjects. However, the relative reduction of individual LDL subtypes differed between these groups. This finding suggests that the effect of atorvastatin on LDL subtype distribution depends on the type of underlying hyperlipoproteinemia.\n Copyright 2001 by W.B. Saunders Company", "Previous studies have shown that effects on high-density lipoprotein cholesterol (HDL-C) may differ among statins.\n A multicenter, randomized, double-blind, parallel-dose study was conducted in 917 hypercholesterolemic patients to compare the efficacy of 80 mg/d simvastatin versus 80 mg/d atorvastatin on HDL-C and apolipoprotein (apo) A-I for 24 weeks. Efficacy was assessed as the means of weeks 6 and 12 and weeks 18 and 24. Prespecified subgroups analyzed were patients with low HDL-C levels and with the metabolic syndrome.\n Simvastatin increased HDL-C and apo A-I values significantly more than did atorvastatin for the mean of weeks 6 and 12 (8.9% vs 3.6% and 4.9% vs -0.9%, respectively) and the mean of weeks 18 and 24 (8.3% vs 4.2% and 3.7% vs -1.4%). These differences were observed across both baseline HDL-C subgroups (<40 mg/dL, > or =40 mg/dL) and in patients with the metabolic syndrome. Low-density lipoprotein cholesterol and triglyceride reductions were greater with atorvastatin. Consecutive elevations >3x the upper limit of normal in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) occurred in significantly fewer patients treated with simvastatin than with atorvastatin (2/453 [0.4%] vs 13/464 [2.8%]), with most elevations observed in women taking atorvastatin (11/209 [5.3%] vs 1/199 [0.5%] for simvastatin).\n Simvastatin (80 mg) increased HDL-C and apo A-I significantly more than did atorvastatin (80 mg) in patients with hypercholesterolemia. This advantage was observed regardless of HDL-C level at baseline or the presence of the metabolic syndrome. Significantly fewer consecutive elevations >3x the upper limit of normal in ALT and/or AST occurred in patients receiving simvastatin.", "High-density lipoprotein cholesterol (HDL-C) levels are inversely associated with cardiovascular risk. Cholesteryl ester transfer protein inhibition is one strategy for increasing HDL-C. This study evaluated the lipid-altering efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy or coadministered with atorvastatin in patients with dyslipidemia.\n A total of 589 patients with primary hypercholesterolemia or mixed hyperlipidemia (53.8% of the study population had low HDL-C) were randomized equally to one of 10 groups: 5 groups received background statin therapy of atorvastatin 20 mg and 5 did not, and each of these was randomized to placebo, anacetrapib 10, 40, 150, and 300 mg once daily for 8 weeks. An equal proportion of patients had triglycerides >150 mg/dL in each group.\n For placebo and anacetrapib monotherapy (10, 40, 150, and 300 mg), least squares mean percent changes from baseline to week 8 for low-density lipoprotein cholesterol (LDL-C) were 2%, -16%, -27%, -40%, and -39%, respectively, and for HDL-C were 4%, 44%, 86%, 139%, and 133%, respectively (P < .001 vs placebo for all doses). Coadministration of anacetrapib with atorvastatin produced significant incremental LDL-C reductions and similar HDL-C increases versus atorvastatin monotherapy. For both anacetrapib monotherapy and coadministration with atorvastatin, the LDL-C reductions were similar in patients with baseline triglyceride levels greater than and less than or equal to the median. Anacetrapib was well tolerated, and the incidence of adverse events was similar for placebo and all active treatment groups. There were no increases in systolic or diastolic blood pressure in any treatment arm.\n Anacetrapib, as monotherapy or coadministered with atorvastatin, produced significant reductions in LDL-C and increases in HDL-C; the net result of treatment with anacetrapib + atorvastatin was approximately 70% lowering of LDL-C and more than doubling of HDL-C. Anacetrapib was generally well tolerated with no discernable effect on blood pressure.", "Although patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease (CVD), the roles of lipid-modifying therapies in decreasing CVD risk are unclear. Our aim is to compare the effects of statin and fibrate therapy on arterial function as a risk marker of CVD.\n Double-blind, randomized, placebo-controlled, parallel-group study.\n Ambulatory patients with stages 3 to 5 CKD.\n 6 weeks of atorvastatin, 40 mg/d, or gemfibrozil, 600 mg twice daily, with placebo.\n Primary outcome was arterial function assessed by means of endothelial-dependent flow-mediated dilatation (FMD) and small-artery compliance (C2). Secondary outcomes included endothelial-independent glyceryl trinitrate-mediated dilatation (GTNMD), large-artery compliance (C1), and levels of lipids, lipoproteins, and oxidized low-density lipoprotein, as well as markers of insulin resistance and inflammation.\n Compared with placebo, atorvastatin significantly decreased low-density lipoprotein (-52%), triglyceride (-30%), and oxidized low-density lipoprotein levels (-41%; P < 0.0001). Gemfibrozil significantly decreased triglyceride levels (-40%) and increased high-density lipoprotein levels (+20%; P < 0.0001). Neither atorvastatin nor gemfibrozil had a significant effect on markers of insulin resistance or inflammation. There was no significant change in FMD, GTNMD, or C1 with either atorvastatin or gemfibrozil. There was improvement in C2 with atorvastatin (+1.1 mL/mm Hg x 100) compared with placebo (P = 0.024), but not with gemfibrozil compared with placebo.\n Small sample size leading to inadequate power, short duration of therapy, and use of a heterogeneous group of patients with CKD and dialysis patients.\n In patients with advanced CKD, atorvastatin is associated with improvement in dyslipidemia and small-artery stiffness, but not endothelial function. Gemfibrozil improves dyslipidemia, but has no effect on arterial function.", "Inflammatory reactions in coronary plaques play an important role in the pathogenesis of acute atherothrombotic events. The most powerful class of lipid-lowering drugs available-statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors)--have additional actions, unrelated to cholesterol reduction, including anti-inflammatory and immunomodulatory properties. This study sought to determine if atorvastatin affects monocyte and lymphocyte activation in patients with unstable angina and mild primary hypercholesterolemia. Following a 4-weeks hypolipemiant-free baseline period, 22 patients-12 with unstable angina (UA) and 10 patients with stable coronary heart disease (SCHD) - were treated with Atorvastatin 20 mg/day. Lipopolysaccharide (LPS)-receptor (CD14) and HLA-DR expression on monocytes and beta-integrins (CD11b, 11c, 49d) on monocytes and lymphocytes were measured by flow cytometry before and after treatment with atorvastatin for 8 weeks. Monocyte CD11b, 11c and CD14 expression and T lymphocytes CD11b expression were significantly (p < 0.001) higher in UA patients before treatment when compared with that in SCHD patients. In patients with UA, they decreased markedly with atorvastatin treatment. The reduction in expression of adhesion molecule on monocytes and lymphocytes and the concentrations of CRP and sICAM-1 may crucially contribute to the clinical benefit of atorvastatin in coronary artery disease, independent of cholesterol lowering effects.", "Isoprostanes are the product of free radical oxidation of arachidonic acid, whose hydrolysis from phospholipids is presumably catalysed by phospholipases A(2) (PLA(2)s) such as group IIA or V PLA(2)s, or group VII PLA(2)[platelet-activating factor acetylhydrolase (PAF-AH), lipoprotein-associated phospholipase]. Atorvastatin reduces concentrations of low-density lipoprotein (LDL), with which PAF-AH is associated, and PLA(2)s' protein concentrations. We investigated the effect of atorvastatin on PLA(2)s and PAF-AH activity and the urinary excretion of 15-F(2trans)-isoprostane (15-F(2t)-IsoP, 8-iso-PGF(2alpha), iPF(2alpha)-III).\n Twenty-four hypercholesterolaemic individuals naive to lipid-lowering therapy were randomized to atorvastatin 40 mg or placebo for 6 weeks. The 15-F(2t)-isoP urinary excretion (gas chromatography/mass spectrometry), PAF-AH and group IIA and V PLA(2) activities (photometry) were assessed at baseline and end-point.\n At end-point, 15-F(2t)-isoP urinary excretion concentrations as well as PLA(2)s' activity were unchanged under atorvastatin (mean change 0.21 +/- 1.79 ng h(-1), 95% confidence interval -0.92, 1.35 and 0.33 +/- 0.94 nmol min(-1) ml(-1), -0.27, 0.93) and under placebo (mean change 0.69 +/- 1.69 ng h(-1), -0.52, 1.90 and 1.29 +/- 2.16 nmol min(-1) ml(-1), -0.25, 2.84). Atorvastatin treatment decreased total (P < 0.001) and LDL-cholesterol (P < 0.001) but had no effect on high-density lipoprotein. PAF-AH activity was lowered in the atorvastatin group (mean change - 5.27+/- 1.96 nmol min(-1) ml(-1), -6.51, -4.03, P < 0.001) but not in the placebo group (mean change 1.02 +/- 1.64 nmol min(-1) ml(-1), 0.15, 2.20), and the change in PAF-AH activity was correlated with that in total (P = 0.03) and LDL-cholesterol (P = 0.03).\n Our results show a lowering effect of atorvastatin on PAF-AH activity associated with its lipid-lowering effect and exclude a key role of PAF-AH in the liberation of 15-F(2t)-isoP from phospholipids.", "Atorvastatin, a new enantiomerically pure synthetic statin, has shown a marked low-density lipoprotein (LDL) cholesterol reduction at doses ranging from 10 to 80 mg/d. This trial was designed to compare the efficacy of atorvastatin 10 mg with simvastatin 10 mg and 20 mg, the latter dose being commonly used in some countries.\n A parallel group, randomized, PROBE, multicenter study was conducted to compare the efficacy of 10 mg/d atorvastatin with that of 10 mg/d simvastatin and 20 mg/d simvastatin in patients with primary hypercholesterolemia. After a 6-week diet-placebo lead-in period, 272 patients with LDL cholesterol > or = 160 mg/dL and triglycerides < or = 300 mg/dL were randomized to 6 weeks of treatment with atorvastatin 10 mg (109 patients), simvastatin 20 mg (109 patients), or simvastatin 10 mg (54 patients). In the main analysis, which tested the equivalence of atorvastatin 10 mg and simvastatin 20 mg, the mean percent change in LDL cholesterol for atorvastatin 10 mg (-37.0%) was greater than and not equivalent to simvastatin 20 mg (-33.8%). In the secondary analysis, which compared the efficacy of atorvastatin 10 mg with that of simvastatin 10 mg, the mean decrease in LDL cholesterol was significantly greater (P < .001) for atorvastatin 10 mg than for simvastatin 10 mg (-37.0% vs. -28.9%). The two drugs were well tolerated, with an incidence of clinical and biochemical side effects similar among the 3 treatment groups.\n In primary hypercholesterolemia, atorvastatin 10 mg was more effective and nonequivalent to simvastatin 20 mg and significantly more effective than simvastatin 10 mg for reducing LDL cholesterol levels.", "Diabetes mellitus and hypercholesterolaemia increase the risk for coronary heart disease, with type 2 diabetes mellitus being the most prevalent form of diabetes, frequently accompanied by dyslipidaemia. The main goal of dyslipidaemia control in nondiabetic and diabetic patients is to lower elevated low-density lipoprotein-cholesterol (LDL-C) levels. Policosanol is a cholesterol-lowering drug, purified from sugarcane wax, with a therapeutic range of 5-20 mg/day, which significantly reduces LDL-C levels. Atorvastatin is an HMG-CoA reductase inhibitor that, across its dose range (10-80 mg/day), has shown significantly greater lipid-lowering effects than all previously marketed statins.\n To compare the effects on lipid profile and platelet aggregation of policosanol and atorvastatin in patients with dyslipidaemia due to type 2 diabetes.\n This randomised, single-blind, parallel-group study was conducted in patients with type 2 diabetes (fasting glucose </=7 mmol/L and glycosylated haemoglobin [HbA(1c)] <8.5%) and high LDL-C levels (>/=3.0 mmol/L). After 6 weeks on a cholesterol-lowering diet, 40 patients were randomised to policosanol or atorvastatin 10mg tablets taken once daily with the evening meal for 8 weeks. Assessments of lipid profile, platelet aggregation tests, safety indicators and adverse events were performed.\n After 8 weeks of therapy, policosanol significantly lowered LDL-C by 25.7% (p < 0.0001 versus baseline) and total cholesterol (TC) by 18.2% (p < 0.001 versus baseline). In turn, atorvastatin 10 mg/day decreased LDL-C by 41.9% and TC by 31.5% (p < 0.0001 versus baseline). Atorvastatin was more effective than policosanol in reducing LDL-C and TC (p < 0.001). Policosanol also significantly reduced the TC/high-density lipoprotein-cholesterol (HDL-C) ratio (25.2%; p < 0.0001) and triglycerides (15.6%; p < 0.001), while atorvastatin lowered TC/HDL-C by 30.5% (p < 0.0001) and triglycerides by 13.9% (p < 0.001); the reductions on these variables were similar in the two groups. Policosanol, but not atorvastatin, significantly increased HDL-C (11.1%; p < 0.01), the effect being significantly different from that of atorvastatin (p < 0.0001). Also, policosanol, but not atorvastatin, significantly inhibited platelet aggregation induced by arachidonic acid 0.75 and 1.5 mmol/L (39.0% and 33.3%, respectively) and by collagen 0.25 and 0.5 mug/mL (15.7% and 28.5%, respectively) [p < 0.001]; these inhibitions were significantly different (p < 0.05) from the changes that occurred with atorvastatin. Neither drug significantly changed platelet aggregation elicited by adenosine diphosphate (ADP). Both treatments were well tolerated, with glycaemic control being unaffected. Neither drug impaired physical safety indicators or glucose control indicators (fasting glucose and HbA(1c)). Atorvastatin significantly increased levels of alanine aminotransferase (ALT) [p < 0.05] and creatine phosphokinase (CPK) [p < 0.01], while policosanol did not significantly change any safety indicator. Only three atorva-statin recipients showed individual values of ALT and CPK that were moderately enhanced (<3 times above the normal upper limit). No patients withdrew from the study. Four patients reported adverse events: two policosanol (insomnia and pruritus) and two atorvastatin (myalgia and raised arterial blood pressure) recipients.\n Policosanol (10 mg/day) for 8 weeks was less effective than similar doses of atorvastatin in reducing LDL-C and TC in patients with dyslipidaemia due to type 2 diabetes, but more effective in increasing HDL-C. Both drugs similarly reduced the TC/HDL-C ratio and triglycerides. Policosanol showed additional advantages regarding inhibition of platelet aggregation. Nevertheless, further studies of longer duration and using dose-titration schemes to achieve LDL-C goals are needed for wider conclusions about the respective effects of these two drugs in such a population subset.", "Elevation of plasma cholesterol and/or triglycerides, and the prevalence of small dense low density lipoproteins (LDL) particles remarkably increase the risk in patients with familial combined hyperlipidemia (FCHL). There are, at present, inconsistent data on the effects of different treatments on size and density of LDL particles in FCHL patients.\n A multicenter, randomized, double-blind, double-dummy, parallel group study was designed to evaluate the effect of 3 months' treatment with atorvastatin (10mg/day) or pravastatin (20mg/day) on the lipid/lipoprotein profile and LDL size in a total of 86 FCHL patients. Both statins significantly lowered plasma total and LDL cholesterol, with a significantly higher hypocholesterolemic effect observed with atorvastatin (-26.8+/-11.1% and -35.9+/-11.1%, respectively) compared to pravastatin (-17.6+/-11.1% and -24.5+/-10.2%). The percent decrease in plasma triglycerides was highly variable, but more pronounced with atorvastatin (-19.8+/-29.2%) than with pravastatin (-5.3+/-48.6%). Opposite changes in LDL size were seen with the 2 treatments, with increased mean LDL particle diameter with atorvastatin, and decreased diameter with pravastatin, and significant between treatment difference in terms of percent modification vs baseline (+0.5+/-1.6% with atorvastatin vs -0.3+/-1.8% with pravastatin).\n The present results support the evidence indicative of a greater hypocholesterolemic effect of atorvastatin compared to pravastatin, and in addition show a raising effect of atorvastatin on the size of LDL particles in FCHL patients.", "To evaluate attainment of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein cholesterol (LDL-C) goal of less than 100 mg/dL with statin treatments in managed care patients at high risk for coronary heart disease.\n In a randomized, open-label, multicenter trial (SOLAR [Satisfying Optimal LDL-C ATP III goals with Rosuvastatin]) performed at 145 US clinical centers from June 5, 2002 to July 12, 2004, high-risk men and women in a managed care population received typical starting doses of rosuvastatin (10 mg/d), atorvastatin (10 mg/d), or simvastatin (20 mg/d) for 6 weeks. Those who did not meet the LDL-C target of less than 100 mg/dL at 6 weeks had their dose titrated (doubled), and all patients were followed up for another 6 weeks.\n A total of 1632 patients were randomized to 1 of the 3 treatment regimens. After 6 weeks, 65% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 41% with atorvastatin and 39% with simvastatin (P<.001 vs rosuvastatin for both). After 12 weeks, 76% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 58% with atorvastatin and 53% with simvastatin (P<.001 vs rosuvastatin for both). Reductions in the LDL-C level, total cholesterol level, non-high-density lipoprotein cholesterol (non-HDL-C) level, and non-HDL-C/HDL-C ratio were significantly greater with rosuvastatin at both 6 and 12 weeks compared with the other statins. Adverse events were similar in type and frequency in all treatment groups, and only 3% of all patients discontinued treatment because of adverse events. No myopathy was observed, no clinically important impact on renal function was attributed to study medications, and clinically important increases in serum transaminases were rare.\n In a managed care population, 10 mg of rosuvastatin treatment resulted in more patients reaching the NCEP ATP III LDL-C goal compared with 10 mg of atorvastatin and 20 mg of simvastatin, potentially reducing the need for titration visits." ]

[ "15327620", "11531635" ]

[ "Misoprostol in the treatment of postpartum haemorrhage in addition to routine management: a placebo randomised controlled trial.", "A randomized study comparing rectally administered misoprostol versus Syntometrine combined with an oxytocin infusion for the cessation of primary post partum hemorrhage." ]

[ "Postpartum haemorrhage remains a leading cause of maternal mortality, despite treatment with conventional methods. In this randomised controlled trial, we compared misoprostol 600 microg (200 microg orally and 400 microg sublingually) with placebo in the treatment of postpartum haemorrhage in addition to routine treatment. One hundred and sixty consenting women who delivered vaginally with measured blood loss > or =500 mL and for whom inadequate uterine contraction was thought to be a possible factor were given either misoprostol or placebo in addition to normal treatment and after routine active management with uterotonics. Blood loss was measured by collection in a special plastic bedpan and side effects of treatment were recorded. Measured average additional blood loss was 325 mL (95% confidence interval [CI] 265 to 384 mL) with misoprostol and 410 mL (95% CI 323 to 498 mL) with placebo. No severe side effects were noted in the use of misoprostol.", "Post partum hemorrhage is a major cause of maternal death, particularly in developing countries, and most cases are due to an atonic uterus. Hemorrhage can occur despite active management of the third stage of labor. Presently, misoprostol (Cytotec, Searle Pharmaceuticals) is the only thermostable uterotonic agent potentially available which would be economically beneficial for developing countries where refrigeration of drugs poses a problem. The objective of the study was to compare intra-muscular Syntometrine (Sandoz Pharmaceuticals) (ampoule=5 iu oxytocin and 500 mcg ergometrine maleate) plus Syntocinon (Sandoz Pharmceuticals) (10 iu oxytocin diluted in 500 ml normal saline) intravenous infusion versus 800 mcg misoprostol per rectum for treatment of primary post partum hemorrhage in a developing country.\n Randomized single blinded two-center study, set in both a township and teaching hospital in South Africa. Sixty-four women with primary post partum hemorrhage due to an atonic uterus were recruited. The primary outcome measure was whether the hemorrhage ceased within 20 minutes of administering the first line treatment, once hemorrhage was clinically recognized.\n There was a 28.1% difference between the misoprostol arm and the Syntometrine and Syntocinon arm (p=0.01). This result had a greater than 80% power. Misoprostol performed better.\n 800 mcg misoprostol per rectum is effective at treating primary post partum hemorrhage." ]

[ "6742017", "18476075" ]

[ "Course and treatment of milk stasis, noninfectious inflammation of the breast, and infectious mastitis in nursing women.", "Treatment of sporadic acute puerperal mastitis." ]

[ "In nursing women with inflammatory symptoms of the breast, it has been possible on the basis of leukocyte counts of the milk and quantitative cultivation for bacteria to classify these cases into milk stasis (counts of less than 10(6) leukocytes and less than 10(3) bacteria per milliliter of milk), noninfectious inflammation (counts of greater than 10(6) leukocytes and less than 10(3) bacteria), and infectious mastitis (counts of greater than 10(6) leukocytes and greater than 10(3) bacteria). In the present study the duration and outcome of these cases were observed, and those without intervention were compared to those with treatment that consisted of systematic and intensive emptying of the breast, supplemented in some cases by antibiotic therapy as directed by susceptibility tests of the bacteria. The course of milk stasis was of short duration and the outcome was good independent of treatment. In cases of noninfectious inflammation the symptoms persisted for several days without treatment, and half of the patients developed infectious mastitis. Emptying of the breast resulted in a significant decrease in the duration of symptoms and a significantly improved outcome. Infectious mastitis without treatment was followed by a good result in only 15% of the cases, and 11% developed abscesses. Emptying of the breast increased the rate of a good outcome to 50% and significantly decreased the duration of symptoms. The addition of antibiotic therapy resulted in a good outcome in 96% of the cases and a further significant reduction of the persistence of symptoms.", "The purposes of this study were to compare the efficacy of amoxicillin and cephradine for the treatment of sporadic acute puerperal mastitis (SAPM) and to evaluate the microbiology and clinical parameters of this infection.\n We conducted a prospective, randomized, single-blinded study comparing amoxicillin, 500 mg orally q 8 h for 7 days, and cephradine, 500 mg orally q 6 h for 7 days. The diagnostic criteria for SAPM included a temperature of > or =37.56 (> or =99.6) and erythema and tenderness of the breast(s).\n Twenty-seven consecutive outpatients with SAPM were evaluated for admission to the study, and 25 of these were enrolled. The mean temperature at enrollment was 38.17 (100.7), with a mean WBC count of 11,440/microl. The most frequent bacterial isolates from expressed milk were Staphylococcus aureus (7), staphylococcal species (coagulase negative) (8), and alpha-hemolytic streptococci (4). There were no significant differences between the 2 antibiotic regimens in cure rate, mean days to resolution of symptoms, or recurrence within 30 days. Both of the treatment failures and 1 of the 3 recurrences within 30 days were amoxicillin-treated patients whose cultures grew S. aureus.\n Oral amoxicillin and cephradine appear equally effective in the treatment of SAPM. Staphylococci were the most frequent isolates from the milk of women with mastitis." ]

[ "16181747", "6442321", "11141388", "2692153", "15303634", "12583553", "9817522", "9636854", "2944094", "6436407", "3132383", "7614957", "8666093", "1664833", "1323954", "9447898", "3041830", "1918785", "9758291", "3804901", "11282262", "12975069", "2258338" ]

[ "[Efficacy and safety of pristinamycin vs amoxicillin in community acquired pneumonia in adults].", "[Comparative study of the effectiveness of enoxacin and amoxicillin in bacterial pneumonia by a double blind method].", "[Oral levofloxacin versus intravenous ceftriaxone and amoxicillin/clavulanic acid in the treatment of community-acquired pneumonia that requires hospitalization].", "[Effect and tolerance of ofloxacin in bronchopulmonary infections in comparison with amoxicillin].", "Gemifloxacin once daily for 7 days compared to amoxicillin/clavulanic acid thrice daily for 10 days for the treatment of community-acquired pneumonia of suspected pneumococcal origin.", "Carbapenems in the treatment of severe community-acquired pneumonia in hospitalized elderly patients: a comparative study against standard therapy.", "A comparative study of levofloxacin and ceftriaxone in the treatment of hospitalized patients with pneumonia.", "Once-daily sparfloxacin versus high-dosage amoxicillin in the treatment of community-acquired, suspected pneumococcal pneumonia in adults. Sparfloxacin European Study Group.", "[Initial antibiotherapy in severe bacterial bronchopneumopathies. Randomized study of a new quinolone: pefloxacin].", "[Comparison of DL-8280 and amoxicillin in the treatment of respiratory tract infections].", "Evaluation of roxithromycin (RU-965) versus cephradine in pneumococcal pneumonia.", "Efficacy and safety of azithromycin versus benzylpenicillin or erythromycin in community-acquired pneumonia.", "Treatment of community-acquired pneumonia: a randomized comparison of sparfloxacin, amoxycillin-clavulanic acid and erythromycin.", "The use of oral temafloxacin compared with a parenteral cephalosporin in hospitalized patients with pneumonia.", "Efficacy and safety of temafloxacin versus those of amoxicillin in hospitalized adults with community-acquired pneumonia.", "Clarithromycin versus amoxicillin-clavulanic acid in the treatment of community-acquired pneumonia.", "Prospective study of lower respiratory tract infections in an extended-care nursing home program: potential role of oral ciprofloxacin.", "A randomized study of ciprofloxacin versus ceftriaxone in the treatment of nursing home-acquired lower respiratory tract infections.", "Trovafloxacin versus high-dose amoxicillin (1 g three times daily) in the treatment of community-acquired bacterial pneumonia.", "Efficacy and safety of ciprofloxacin in patients with respiratory infections in comparison with amoxycillin.", "An open, randomised, multi-centre study comparing the safety and efficacy of sitafloxacin and imipenem/cilastatin in the intravenous treatment of hospitalised patients with pneumonia.", "[A comparison of moxifloxacin and amoxicillin in the treatment of community-acquired pneumonia in Latin America: results of a multicenter clinical trial].", "Comparison of pefloxacin with ceftazidime in severe bronchopulmonary infections." ]

[ "Evaluation of efficacy and safety of pristinamycin (PRI), compared with amoxicillin (AMX), both at 3 g daily for 7 to 10 days in adults with community-acquired pneumonia (CAP).\n Multinational, randomized, double blind, double dummy clinical trial of non-inferiority was conducted in 399 patients with a CAP.\n At inclusion, the mean age was 47.8+/-18.3 years, 24.3% patients were 65 or older. The Fine score was < or =III in 85.4% patients. The bacterial etiology was documented in 34.8% of patients: Streptococcus pneumoniae (48.1%), Mycoplasma pneumoniae (18.6%), Haemophilus influenzae (14.7%), Chlamydia pneumoniae (13.2%), Legionella pneumophila (9.3%). In the clinical per-protocol population, the clinical success rate was 87.6% in each group: 149/170 patients (PRI) and 148/169 (AMX); The 95% confidence interval was [-6.61%; 7.23%]. In modified intend to treat population, the clinical success rate was 79.9% (151/189) in the PRI group and 83.0% (151/182) in the AMX group [CI 95% (-10.87%; 4.69%)]. A satisfactory bacteriological response was observed in 82.3% (51/62) of PRI patients and 88.1% (59/67) of AMX patients. Treatment related adverse events occurred similarly in both groups according to the expected tolerance profile of the two drugs. No serious adverse events in both groups were related to the study drugs.\n In this study, PRI 3 g daily was clinically as effective and well tolerated as AMX 3 g daily, for 7 to 10 days, in PPc, in the treatment of bacterial community-acquired pneumonia.", "nan", "Levofloxacin, an antibiotic from the quinolone family, which is used with success in the ambulatory treatment of patients with community-acquired pneumonia, has been recently introduced to the pharmaceutical market. The purpose of this study was to compare the effectiveness and tolerance of oral (v.o.) levofloxacin (LVF) versus intravenous (i.v.) amoxicillin/clavulanate (AMX/CL) and ceftriaxone (CTX) in the treatment of the community-acquired pneumonia that require hospitalization (CAPH).\n In this prospective and randomized study 84 patients were included, 28 per group, from both sex with CAPH. The patients were assigned randomly to receive one of the next treatments: AMX/CL, 1.02 g i.v. every 8 h, CTX, 1 g i.v. every 12 h or LVF, 500 mg v.o. every 24 h. At the beginning clinical, biochemical and radiological characteristics were recorded from each case and at the 72 h the effect of treatment was evaluated using the evolution of the thermal curve and radiological images. The quantitative variables were analyzed with ANOVA, the qualitatives parameters with *2 test and Yates correction. The level of signification was * = 0.05.\n Age, sex, clinical presentation, biochemical measurements and radiological images in the 3 groups were similar and no adverse effects were recorded in any of them. Number of patients with favorable outcome in the groups AMX/CL, CTX and LVF was 25 (89%), 25 (89%) and 26 (93%); p = 0,870.\n Levofloxacin can be a simple, effective and safe therapeutic option for patients with CAPH.", "Ofloxacin and amoxicillin in the treatment of 121 bronchopulmonary infections were compared in a randomized, open clinical trial. 64% of the infections were pneumonias. S. pneumoniae, H. influenzae and B. catarrhalis accounted for 76% of the etiologic agents. The clinical and bacteriological responses were positive in more than 90% of the patients and comparable in both groups. None of the isolated agents was resistant to ofloxacin, whereas 21% were amoxicillin-resistant. Ofloxacin was used without randomization in the treatment of 26 atypical pneumonias and opportunistic infections, all of which were cured or improved. Occurrence of side-effects was rarely observed in either treatment group.", "Community-acquired pneumonia (CAP) is common among adults and contributes considerably to morbidity and mortality.\n To compare the safety and efficacy of gemifloxacin to high-dose amoxicillin/clavulanate for the treatment of CAP of suspected pneumococcal origin.\n Randomized, multicentre, double-blind, double-dummy, parallel group Phase III study.\n From September 1998 to July 1999, 324 patients with CAP were randomized at 102 centers in France, Poland and the Republic of South Africa.\n Patients were double-blind randomized to receive either oral gemifloxacin 320 mg once daily for 7 days or oral amoxicillin/clavulanate 1 g/125 mg three times daily for 10 days.\n The main outcome measures were clinical, bacteriological, and radiological responses at the end of therapy (day 12-14) and follow-up (day 24-30) visits.\n In 228 PP patients, clinical resolution at follow-up was 88.7% for 7-day gemifloxacin and 87.6% for 10-day amoxicillin/clavulanate [95% CI, -7.3, 9.5]. In 249 PP patients, clinical resolution at end of therapy was 95.3% for 7-day gemifloxacin vs. 90.1% for 10-day amoxicillin/clavulanate [95% CI, -1.2, 11.7]. Bacteriologic response rates for the PP patients at end of therapy were 96.3% for 7-day gemifloxacin and 91.8% for the amoxicillin/clavulanate group [95% CI, -4.7, 13.6]. Bacteriologic response rates at follow-up were 87.2% for 7-day gemifloxacin and 89.1% for the amoxicillin/clavulanate group [95% CI, -15.0, 11.2]. Specifically gemifloxacin eradicated 95.7% of Streptococcus pneumoniae including penicillin and macrolide resistant strains. Radiological response rates for the PP patients at end of therapy were 89.1% for 7-day gemifloxacin and 87.6% for the amoxicillin/clavulanate group. The most frequently reported drug-related events were in the gemifloxacin group, diarrhea (6.0%) and rash (3.0%) and in the amoxicillin/clavulanate group, diarrhea (11.1%) and fungal infection, vaginitis and vomiting (each 2.0%). Overall there were statistically fewer withdrawals due to lack of therapeutic effect in the gemifloxacin group compared with the amoxicillin/clavulanate cohort, (95% CI, -8.8;0.6; P = 0.03).\n Gemifloxacin 320 mg once daily for 7 days was found to be clinically, bacteriologically, and radiologically as effective as 10 days of amoxicillin/clavulanate 1 g/125 mg three times daily for the treatment of suspected pneumococcal CAP.", "In this open, prospective, study were enrolled 204 hospitalized elderly patients with severe (88 males, 116 females, age range 70-94). Patients were randomized to receive one of the following antibiotic treatment regimens: meropenem 500 mg i.v. t.i.d. (52); imipenem/cilastatin 500 mg i.v. t.i.d. (51), clarithromycin 500 mg + ceftriaxone 1 g i.v. b.i.d. (52), clarithromycin 500 mg + amikacin 250 mg i.v. b.i.d. (49). In 99 cases causative germs were isolated (24 meropenem, 26 imipenem, 23 clarithromycin + ceftriaxone, 26 ceftriaxone + amikacin). A satisfactory clinical, bacteriological response was achieved respectively in 86.5% 77% in meropenem; 86.3% 71% in imipenem/cilastatin; 69% 61% in ceftriaxone + clarithromycin and in 85.7% 77% in clarithromycin + amikacin. The mean total cost for each patient was $1,560; $1,620; $1,760 and $1,792 in meropenem, imipenem/cilastatin, clarithromycin + ceftriaxone and clarithromycin + amikacin respectively. This study shows that treatment with either meropenem or imipenem is as efficacious as conventional therapy in the treatment of community acquired pneumonia (CAP), and that meropenem is the most cost-effective.", "A multinational, multicentre, open, randomised study in hospitalised patients with pneumonia compared levofloxacin 500 mg twice daily with ceftriaxone 4 g i.v. once daily. Levofloxacin patients started on i.v. treatment and switched to oral on d 3-5 of therapy if signs and symptoms had improved. The minimum treatment duration was 5 d, except for treatment failure, and the median 8 d. The primary efficacy analysis was based on the per-protocol assessment of the clinical cure rate determined 2-5 d after the end of treatment in the per-protocol (PP) population (levofloxacin 127, ceftriaxone 139). Of 625 patients enrolled and randomized, 6 received no treatment, giving an intention-to-treat (ITT) population of 619 (levofloxacin 314, ceftriaxone 305). At the clinical endpoint, 2-5 d after the end of treatment, the cure rates for levofloxacin and ceftriaxone were similar in both the ITT (76% and 75%, respectively) and PP (87% and 86%, respectively) populations. Both drugs were well tolerated. Twice-daily levofloxacin 500 mg, either i.v. or as sequential i.v./oral therapy, was as effective as i.v. once-daily ceftriaxone 4 g in the treatment of hospitalized patients with pneumonia and offers the advantage of sequential therapy.", "The objective of this randomized, double-blind, multicenter study of 329 adult patients requiring hospitalization was to compare the safety and efficacy of sparfloxacin at a dosage of 200 mg once daily (following a 400-mg loading dose on day 1) with those of amoxicillin given as a 1-g oral dose three times daily for treatment of community-acquired pneumonia suspected to be due to Streptococcus pneumoniae. Success of treatment was determined by a combination of clinical assessment and chest radiography. Pneumococcal pneumonia was the confirmed diagnosis for 177 patients (54%). Overall rates of success among evaluable patients were equivalent between drugs, both at the end of treatment (sparfloxacin, 92%; amoxicillin, 87%) and at follow-up (sparfloxacin, 89%; amoxicillin, 84%). Sparfloxacin was well-tolerated and produced fewer gastrointestinal effects than amoxicillin. In conclusion, sparfloxacin is a safe and effective alternative to high-dose amoxicillin for the treatment of suspected pneumococcal community-acquired pneumonia.", "nan", "nan", "One hundred and sixty black South African gold miners with acute pneumococcal pneumonia were enrolled in a prospective randomized double-blind trial comparing roxithromycin (150 mg 2 X day) with cephradine (1.0 g 2 X day). Ninety patients with pneumonia caused by Streptococcus pneumoniae were treated for 5-10 days. Forty-three of 46 (93.4%) of the roxithromycin and all 44 (100%) of the cephradine treated groups had satisfactory clinical responses. In eight of the 46 (17%) roxithromycin treated patients and 10 of the 44 (23%) cephradine treated patients, Streptococcus pneumoniae was not eradicated from sputum cultures by the tenth day. Side effects in 18 patients (20%) were mild and were usually manifested by elevation of the transaminases; these were more common in the cephradine group (12) than in the roxithromycin group (5). Roxithromycin appears to be a safe and effective oral antibiotic for treatment of patients with mild to moderate pneumococcal pneumonia.", "Azithromycin, a recently introduced antibiotic, offers the potential advantages of short-course administration and lower toxicity compared to other macrolides. Approved for the treatment of mild pneumonia, this drug was investigated in a study of patients hospitalized for community-acquired pneumonia. In an open-labelled randomized study, oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumococcal pneumonia. Azithromycin was also compared with erythromycin, both administered orally, in all other patients. Three hundred thirty-four patients with community-acquired pneumonia were hospitalized, 108 of whom were randomized; 104 could be evaluated. A need for intravenous therapy was the most common reason for exclusion. In the pneumococcal group, 35 patients received azithromycin and 29 benzylpenicillin. The clinical and radiological success rate achieved with azithromycin (83%) was considerably higher than that achieved with benzylpenicillin (66%), though the difference was not significant. In the non-pneumococcal group, 19 patients received azithromycin and 21 erythromycin; no differences in the success rate were found (79% and 76%, respectively). Eight patients on azithromycin had a blood culture positive for Streptococcus pneumoniae; in three of these patients therapy was changed. None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy. It is concluded that oral azithromycin, administered as short-course therapy, is an appropriate antibiotic for treating patients with community-acquired pneumonia. However, it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia.", "The treatment of community-acquired pneumonia is empirical in most cases and must cover a wide range of potential pathogens, such as Streptococcus pneumoniae, including penicillin-resistant strains, Haemophilus influenzae and intracellular microorganisms. The objective of this double-blind, randomized, parallel group study was to compare the efficacy and safety of sparfloxacin (400 mg loading dose, followed by 200 mg o.d.) with that of oral amoxycillin-clavulanic acid (500/125 mg t.i.d.) or oral erythromycin (1 g b.i.d.), during 7-14 days in 808 patients with confirmed community-acquired pneumonia. The overall success rates for sparfloxacin (87%), amoxycillin-clavulanic acid (80%) and erythromycin (85%) were similar in evaluable patients, and the equivalence hypothesis used for the statistical analysis showed at least an equivalent efficacy for the three antibiotics tested. The analysis of microbiologically documented infections (40% of the patients) showed that overall success rates were similar for S. pneumoniae and H. influenzae infections. Treatment withdrawal was necessary in 3.5, 2.5 and 7.7% of the patients treated with sparfloxacin, amoxycillin-clavulanic acid and erythromycin, respectively. This study indicates that sparfloxacin was at least as effective as amoxycillin-clavulanic acid or erythromycin in the treatment of mild-to-moderate community-acquired pneumonia and that the adverse effects were similar in the three groups.", "In a European open, multicentre, prospective clinical trial, 100 hospitalized adult patients (61 males; 18-91 years old (mean age 62] with bacterial pneumonia, diagnosed clinically and radiographically, were randomized to receive either oral temafloxacin 600 mg twice daily (n = 49) or intravenous cefotaxime 2 g thrice daily (n = 51). Signs, symptoms and chest radiographs were assessed during, at the end of therapy and at follow-up eight to ten days after the last dose. Patients were treated for a maximum of ten days. Sputum was obtained for culture before, during and after therapy. The clinical cure rate for the temafloxacin treatment group was 90%, the bacteriological cure rate was 91% and the radiological response rate was 95%. The respective rates for the cefotaxime-treated group were 92%, 96% and 100%. There were no significant differences between the treatment groups for clinical or microbiological outcome, premature study discontinuation, or adverse events. Oral temafloxacin was clinically and bacteriologically equivalent to intravenous cefotaxime in the treatment of hospitalized adults with bacterial pneumonia.", "Temafloxacin, a new fluoroquinolone, was compared with amoxicillin in the treatment of adult hospitalized patients with community-acquired pneumonia. In this double-blind, multicenter study, patients were randomly assigned to treatment with temafloxacin at 600 mg twice daily (n = 125) or amoxicillin at 500 mg three times daily (n = 121); the average duration of treatment was 10 days. Clinical recovery rates were similar for patients treated with temafloxacin and amoxicillin (89 and 85%), as were bacterial eradication rates (99 and 97%). This was also true for subgroups of patients with pneumococcal pneumonia (n = 100), nonpneumococcal pneumonia (n = 122), or atypical pneumonia (n = 12). Outcomes for temafloxacin- and amoxicillin-treated patients were also similar in terms of defervescence, improvement in leukocytosis, and radiographic evidence of infection. The frequency and severity of adverse events were similar in both groups, consisting primarily of digestive disorders and skin manifestations. We conclude that temafloxacin may be recommended as an alternative antibacterial drug for patients with suspected pneumococcal pneumonia who fail to respond to benzylpenicillin or amoxicillin when the incidence of multiresistant pneumococcal strains is low. In countries where the incidence of these strains is high, temafloxacin may also be recommended.", "In an open, prospective, randomised study, the clinical and bacteriological efficacy of intravenously administered clarithromycin was compared with that of amoxicillin-clavulanic acid in 112 patients with community-acquired pneumonia requiring hospitalisation. Clinical cure or improvement occurred in 86% (48/56) of the clarithromycin-treated patients and 84% (47/56) of the amoxicillin-clavulanic acid-treated patients. The rate of bacteriologic eradication was similar for the two drugs as were the rapidity of a clinical response and the rate of improvement of radiological signs. Clarithromycin had a slightly higher rate of side-effects mainly due to phlebitis caused by the intravenous treatment, but treatment could be continued in all cases. Clarithromycin should be used with caution in patients being treated with digoxin because of a significant risk of bradycardia resulting from drug interaction.", "Infections of the lower respiratory tract pose an important problem in nursing homes. Despite the magnitude of this problem, few, if any, antibiotic studies have been targeted specifically at nursing home-acquired bronchopulmonary infections. Following the establishment of a teaching Extended-Care Nursing Home Program, which facilitated the early diagnosis and therapy of bronchopulmonary infections, a comparative trial of oral ciprofloxacin and intramuscular cefamandole was initiated in elderly patients with lower respiratory tract infections. In addition to assessing the relative efficacy and safety of ciprofloxacin and cefamandole, our goals were to identify problems and pitfalls associated with conducting clinical research in this nursing home setting, evaluate selected clinical and laboratory features of lower respiratory tract infection in this patient population, and measure outcomes in all study groups. PATIENTS and\n During a 20-month period, 40 patients with pneumonia and 20 patients with acute bronchitis were enrolled in this randomized study. Sixty-three patients with pneumonia who were ineligible for the randomized study were also followed prospectively. The mean age of the 111 participants (123 cases) was 80.8 years; all patients had at least one chronic medical condition.\n Although Streptococcus pneumoniae was the single most common isolate, gram-negative bacteria were cultured from 81 percent of the cases that yielded pathogens from a satisfactory sputum specimen. The in-hospital mortality rate was strikingly low (6.5 percent), and a large majority of patients in all study groups were discharged safely back to their nursing homes well within the Diagnosis-Related Group length of stay.\n Ciprofloxacin appeared to be as safe and effective as cefamandole in this nursing home program; however, additional studies are needed to determine its role in the treatment of elderly patients with bronchopulmonary infections.", "To compare the efficacy and safety of ciprofloxacin and ceftriaxone in patients with nursing home-acquired lower respiratory tract infections requiring initial hospitalization.\n Prospective, randomized trial.\n Extended care nursing homes affiliated with a teaching hospital.\n Fifty patients aged 60 years or older with normal or mildly impaired renal function admitted to the hospital for treatment of lower respiratory tract infections.\n Twenty-four patients received initial therapy with intravenous ciprofloxacin, 200 mg every 12 hours (19 patients) or 400 mg every 12 hours (5 patients) during the acute phase followed by 750 mg orally every 12 hours during the convalescence phase. Twenty-six patients received initial therapy with intravenous ceftriaxone, 2 g every 24 hours during the acute phase followed by 1 g administered intramuscularly every 24 hours during the convalescent phase. The total duration of therapy was 14 days.\n Successful outcome was defined as resolution or marked improvement in clinical signs and symptoms of lower respiratory tract infection upon completion of the treatment course.\n Twelve (50%) of the ciprofloxacin-treated and 14 (54%) of ceftriaxone-treated patients had successful outcomes. Recurrent oropharyngeal aspiration was the reason for treatment failure in most patients refractory to either antibiotic. Mortality during therapy was 8% in each group. From 21 satisfactory sputum specimens collected, S. pneumoniae was the most common isolate, followed by H. influenzae and other Gram-negative bacteria. Ciprofloxacin therapy was well tolerated; ceftriaxone therapy was discontinued in two patients (8%) due to adverse reactions (intramuscular pain and drug fever).\n Sequential intravenous/oral ciprofloxacin appears to be as safe and effective as sequential intravenous/intramuscular ceftriaxone. The optimal dosage of intravenous ciprofloxacin in this patient population appears to be 400 mg every 12 hours; however, additional clinical and pharmacokinetic studies with this regimen are warranted.", "Once-daily trovafloxacin 200 mg was compared with high-dose amoxicillin, 1 g three times daily, given for 7 to 10 days. At end of treatment (day 10), the response was clinically successful (cure + improvement) in 93% of 152 clinically evaluable trovafloxacin patients and in 89% of 160 amoxicillin patients. At study end (day 35), respective rates were 91% and 81% (95% confidence interval: 1.6, 17.6; P=0.01). In evaluable patients with positive baseline radiographs, 93% of trovafloxacin and 88% of amoxicillin patients demonstrated radiological resolution at end of treatment. Streptococcus pneumoniae and Haemophilus influenzae eradication rates were comparable at end of treatment in both treatment groups, but at study end Streptococcus pneumoniae eradication rates were higher in trovafloxacin patients (100% vs 81%). At study end, all four trovafloxacin patients with baseline penicillin-resistant Streptococcus pneumoniae were clinically cured with pathogen eradication, whereas two of five amoxicillin patients with baseline penicillin-resistant Streptococcus pneumoniae were clinical failures with pathogen persistence. For patients in whom no pathogen was identified, trovafloxacin was significantly more effective at end of treatment (P=0.096) and study end (P=0.013). Treatment-related adverse events were comparable; the most common were headache, vomiting and dizziness in trovafloxacin patients, and diarrhoea. headache and abdominal pain in amoxicillin patients.", "Ciprofloxacin and amoxycillin were compared in the treatment of respiratory infections (pneumonia, acute bronchitis, exacerbation of chronic lung disease) in a study of 48 patients randomly assigned to ten days treatment with standard doses of either drug. Forty-eight patients were evaluated, 26 in the ciprofloxacin group and 22 in the amoxycillin group. The response to therapy was judged by clinical and bacteriological criteria. Ciprofloxacin was as effective as amoxycillin with a successful outcome in 81% and 82% of cases respectively. A specific bacterial cause was determined in just over half the cases (28 patients) and eradication rates were higher for ciprofloxacin than for amoxycillin, 87% and 64% respectively. In particular, amoxycillin was unsuccessful in two patients infected with Branhamella catarrhalis. Both regimens were safe and produced little, if any, adverse effect (one possible episode in each treatment group). Ciprofloxacin was found to be as effective in bacterial respiratory tract infections as amoxycillin.", "This was a phase II, randomised, open-label, multi-centre study to assess the safety, tolerability, and efficacy of sitafloxacin (DU-6859a, 400 mg once daily) compared with imipenem (imipenem/cilastatin, 500 mg three times daily) in the treatment of hospitalised patients with pneumonia. Patients (n=69) were entered into the study in the intent-to-treat group, 35 in the sitafloxacin and 34 in the imipenem group. Patients (n=65) were included in the clinically evaluable population and 42 in the bacteriologically evaluable population. Baseline demographic data and clinical characteristics were similar for both treatment groups and across all patient populations. The incidence, severity and type of adverse events were similar in both treatment groups. The frequency of adverse events, which were considered to be related to the study of drugs was low and generally similar between the two groups. Mild transient increases in alanine aminotransferase and alkaline phosphatase occurred in the sitafloxacin treatment group, but there were no apparent trends in the other serum enzyme levels. The clinical response at the first and second follow-up assessments indicated that 94-97% of patients in the clinically evaluable population and 91% of patients in the intent-to-treat population were classified as cured in both treatment groups. The bacteriological response was classified as satisfactory for all patients (100%) in the bacteriologically evaluable population in the imipenem treatment group and satisfactory for 90 and 95% of cases at the first and second follow-up assessments in the bacteriologically evaluable population in the sitafloxacin treatment group, respectively. In conclusion, for the treatment of pneumonia, sitafloxacin was considered as safe and as tolerable as imipenem and preliminary data from this study suggest that it may have similar efficacy.", "Since community-acquired pneumonia (CAP) is a common disease with a high morbidity rate, it is important to obtain information concerning its etiology and susceptibility to antibiotics across different geographic areas. This study presents data obtained in 5 Latin American counties in the course of an international clinical trial that evaluated the efficacy and safety of treatment with either moxifloxacin or amoxicillin administered for 10 days to patients suspected of having CAP caused by a pneumococcal infection. Details are given of the pathogens identified, the patterns of sensitivity to antibiotics observed, and the clinical and microbiological results obtained.A total of 84 patients were studied, of whom 70 (83.3%) were evaluated at the end of the trial to determine the efficacy and safety of the treatment received. Gram-positive bacteria were found in samples from 29 patients (80.5%). The pathogen was Streptococcus pneumoniae in 28 of those cases (77.7%). Gram-negative bacteria were found in 7 patients (19.4%), the most common being Haemophilus influenzae in 3 patients (8.3%). The presence of atypical microorganisms was detected in 18 of the 70 patients (25%), mainly Mycobacterium pneumoniae (n=11), and in 6 cases (8.5%) the infection was mixed. Ten strains of S. pneumoniae (35.7%) were shown to be susceptible to penicillin, 2 (7.1%) were highly resistant, and 16 (57.1%) showed moderate resistance. The clinical success rate at the final visit after treatment was 94.1% for moxifloxacin and 91.7% for amoxicillin. The results of this trial demonstrate a high prevalence of S. pneumoniae with reduced susceptibility to penicillin in patients with CAP in Latin America. It also revealed a high incidence of atypical pathogens and mixed infection in 8.6% of patients. This information should be taken into account when establishing protocols for empirical treatment of CAP in Latin America.", "In a prospective open randomized multicentre trial pefloxacin (400 mg twice daily, orally) or ceftazidime (2 g twice daily iv) were given to 82 and 88 patients, respectively, with serious bronchopulmonary infection, defined as: infection occurring in high risk patients, or infection that had failed to respond to previous antimicrobials, or infection by a multiresistant pathogen. An additional nitroimidazole was allowed if the culture demonstrated the presence of anaerobes considered pathogenic. Efficacy analysis was possible in 139 patients, 70 in the ceftazidime group, 69 in the pefloxacin group. In the efficacy population, 93 bacterial strains were isolated in the pefloxacin group and 89 in the ceftazidime group. There were more Streptococcus spp. in the ceftazidime group (21) than in the pefloxacin group (14) (P = 0.06). A successful clinical response was observed in 45 patients give pefloxacin (65.2%) and 51 patients given ceftazidime (72.9%). The difference was not statistically significant. There were two relapses with pefloxacin and six with ceftazidime. In the pefloxacin group 86 pathogens (91%) and in the ceftazidime group 78 pathogens (88%) were eradicated. There were 18 and 13 adverse reactions with ceftazidime and pefloxacin, respectively. In this study, pefloxacin was as effective and as safe as ceftazidime in the treatment of severe bronchopulmonary infections." ]

[ "15753273", "12712025", "11802044", "18468831", "16732143", "9660281", "15808038", "8427434" ]

[ "Effectiveness of oral dexamethasone in the treatment of moderate to severe pharyngitis in children.", "Oral dexamethasone for the treatment of pain in children with acute pharyngitis: a randomized, double-blind, placebo-controlled trial.", "Efficacy of single-dose dexamethasone as adjuvant therapy for acute pharyngitis.", "Clinical efficacy of dexamethasone for acute exudative pharyngitis.", "A pilot study of 1 versus 3 days of dexamethasone as add-on therapy in children with streptococcal pharyngitis.", "The role of betamethasone in the treatment of acute exudative pharyngitis.", "Adjuvant prednisone therapy in pharyngitis: a randomised controlled trial from general practice.", "Dexamethasone as adjuvant therapy for severe acute pharyngitis." ]

[ "To determine the effectiveness of a single dose of oral dexamethasone in reducing the pain associated with moderate to severe pharyngitis in pediatric patients.\n Prospective, randomized, double-blind, placebo-controlled clinical trial.\n Large, urban pediatric emergency department between March 2002 and November 2003.\n Children aged 5 to 18 years with moderate to severe pharyngitis (odynophagia or dysphagia, moderate to severe pharyngeal erythema or swelling, and a McGrath Facial Affective Scale score of 0.75 or higher [scale 0.0-1.0]).\n Study patients were randomly assigned to receive 1 dose of either oral dexamethasone suspension (0.6 mg/kg with a maximum of 10 mg) or placebo of the same volume. All participants were tested for group A beta-hemolytic streptococcal pharyngitis and treated accordingly. Daily telephone follow-up was conducted until complete resolution of sore throat.\n Primary outcome variables included hours to initial relief of sore throat and time to the complete resolution of pain. Secondary outcome variables included changes in the McGrath Facial Affective Scale score at 24 and 48 hours, persistence of associated symptoms, use of anti-inflammatory or antipyretic medication, and subsequent use of medical resources for dehydration or pain.\n A convenience sample of 150 patients was randomized to receive either dexamethasone (n = 75) or placebo (n = 75). Twenty-five patients were lost to follow-up, leaving 125 patients available for data analysis; 57 received dexamethasone and 68 received placebo. Patients who received dexamethasone reported earlier onset of pain relief (9.2 vs 18.2 hours; P<.001), fewer hours to complete resolution of sore throat (30.3 vs 43.8 hours; P = .04), and larger changes in the McGrath Facial Affective Scale score in the first 24 hours (-0.58 vs -0.43; P = .002). Children who tested negative for group A beta-hemolytic streptococci had greater pain relief with dexamethasone compared with placebo (onset of pain relief, 8.7 vs 24 hours; P = .001), less time to complete resolution of sore throat (37.9 vs 70.8 hours; P = .006), and greater changes in the McGrath Facial Affective Scale score in the first 24 hours (-0.50 vs -0.21; P<.001).\n Children with moderate to severe pharyngitis had earlier onset of pain relief and shorter duration of sore throat when given oral dexamethasone.", "We compare oral dexamethasone with placebo for the relief of pain in children with acute pharyngitis.\n We performed a prospective, randomized, double-blind, placebo-controlled trial of children aged 5 to 16 years who presented to the emergency department with acute pharyngitis. Children rated their pain on a standardized color analog scale and had a rapid streptococcal antigen detection test performed to determine group assignment. Children were randomized to dexamethasone (0.6 mg/kg, maximum dose 10 mg) or placebo. Blinded research assistants called all families daily to determine pain scores until the point of complete pain relief. The primary outcome measures were the time to clinically significant pain relief and the time to complete pain relief.\n A total of 184 children were enrolled in the study. There were 85 children in the antigen-positive group, of whom 45 were randomized to dexamethasone and 40 to placebo. In children with group A beta-hemolytic streptococcal pharyngitis, the median time to clinically significant pain relief was 6 hours in the dexamethasone group versus 11.5 hours in the placebo group (P =.02; effect size of 5.5 hours with 95% confidence interval [CI] of 1.0 and 10.0 hours), and the time to complete pain relief was similar (36 hours for placebo versus 40 hours for dexamethasone, P =.86; effect size of 4.0 hours with 95% CI of -9.3 and 17.3 hours) in the placebo group. There were 99 children enrolled in the antigen-negative group, of whom 47 received dexamethasone and 52 received placebo. In this group, the median time to clinically significant pain relief was 13 hours in the dexamethasone group versus 9 hours in the placebo group (P =.32; effect size of 4 hours with 95% CI of -2 and 10 hours), and the time to complete pain relief was similar (48 hours for placebo versus 50 hours for dexamethasone, P =.61; effect size of 2 hours with 95% CI of -11.8 and 15.8 hours).\n For all children with acute pharyngitis, oral dexamethasone does not decrease the time to onset of clinically significant pain relief or time to complete pain relief. However, in the subset of children with positive antigen detection test results, there is a statistically significant improvement in time to onset of pain relief, but it is of marginal clinical importance.", "Pharyngeal inflammatory pain is reduced by a single dose of dexamethasone.\n Prospective, randomized, double-blinded, placebo-controlled study.\n From August 1998 to July 2000, a total of 118 patients were enrolled. We compared placebo (n = 37), a 10-mg single dose of intramuscular injection of dexamethasone (n = 39), and a 10-mg single dose of oral dexamethasone (n = 42). All patients were given oral antibiotics and had bacterial throat cultures.\n Complete telephone follow-up 12 hours after treatment was available in 111 patients, and 24-hour follow-up data were available in 116. The change in pain visual analogue scale scores (pretreatment score minus 12-h follow-up score) reported by patients who were given either intramuscular (median score, 4; mean score +/- SD, 4.2 +/- 2.3) or oral dexamethasone (median score, 3; mean score +/- SD, 3.8 +/- 2.3) was significantly greater than that of the patients who were given placebo (median score, 2; mean score +/- SD, 2.1 +/- 2.0) (P <.001 and P =.002, respectively). This difference in improvement was also evident when the percentage of change was compared in the three treatment arms at 12-hour and 24-hour follow-up. Patients who were given dexamethasone had the onset of pain relief a median of 4 hours earlier than those who were given oral and intramuscular placebo (P =.029). Statistically significant differences among the three treatment arms were confirmed when a bacterial pathogen was identified (n = 47) but not in a subset that did not have a pathogen identified.\n Single-dose dexamethasone appears to be a safe, effective, and inexpensive adjunctive treatment for acute pharyngitis in patients 15 years of age and older. Patients treated with intramuscular or oral dexamethasone had significant relief of pain (relative to baseline) compared with patients who were given placebo. Identification of a bacterial pathogen had a significant impact on the response to dexamethasone.", "The objective of this study was to investigate whether treatment with single-dose dexamethasone can provide relief of symptoms in acute exudative pharyngitis. A prospective, randomized, double-blinded, placebo-controlled clinical trial was undertaken over a 3-month period in a university-based Emergency Department. The study included all consecutive patients between 18 and 65 years of age presenting with acute exudative pharyngitis, sore throat, odynophagia, or a combination, and with more than two Centor criteria. Each patient was empirically treated with azithromycin and paracetamol for 3 days. The effects of placebo and a fixed single dose (8 mg) of intramuscular injection of dexamethasone were compared. The patients were asked to report the exact time to onset of pain relief and time to complete relief of pain. After completion of the treatment, telephone follow-up regarding the relief of pain was conducted. A total of 103 patients were enrolled. Thirty patients with a history of recent antibiotic use, pregnancy, those who were elderly (>65 years of age) and patients who failed to give informed consent were excluded. Forty-two patients were assigned to the placebo group and 31 were assigned to the intramuscular dexamethasone group (8-mg single dose). Time to perceived onset of pain relief was 8.06+/-4.86 h in steroid-treated patients, as opposed to 19.90+/-9.39 h in the control group (p=0.000). The interval required to become pain-free was 28.97+/-12.00 h in the dexamethasone group, vs. 53.74+/-16.23 h in the placebo group (p=0.000). No significant difference was observed in vital signs between the regimens. No side effects and no new complaints attributable to the dexamethasone and azithromycin were observed. Sore throat and odynophagia in patients with acute exudative pharyngitis may respond better to treatment with an 8-mg single dose of intramuscular dexamethasone accompanied by an antibiotic regimen than to antibiotics alone.", "Studies in adults, but not in children, have shown a beneficial effect of one dose of steroid on the severity and duration of throat pain in acute pharyngitis. The effectiveness of longer steroid treatment has not been evaluated in children.\n We performed a randomized, double-blind, 3-arm, placebo-controlled trial to estimate the effectiveness of one dose versus 3 daily doses of oral dexamethasone in the treatment of 4- to 21-year-old patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis. Participants used the Wong-Baker FACES scale to rate their symptoms at enrollment and twice daily for 5 days. Patient-completed diaries and telephone interviews provided follow-up data. Primary end points-severity of throat pain, improvement in general condition and improvement in activity level-were evaluated by survival analysis.\n Ninety patients were enrolled. For each end point, we rejected the null hypothesis of a common survival experience for the 3 study arms. With the exception of 2 days for throat pain in participants receiving one dose of dexamethasone, the median time to improvement for all end points was 1 day for both arms of dexamethasone and 2 days for placebo. There was no difference between study arms in return to a clinical setting for symptoms related to GABHS pharyngitis or absenteeism from work/school. No patient experienced complications related to GABHS pharyngitis in the 30 days after enrollment.\n In this pilot study, children with GABHS pharyngitis who receive dexamethasone as add-on therapy have a more rapid improvement in general condition and level of activity and, for those receiving 3 daily doses of dexamethasone, in resolution of throat pain.", "To compare betamethasone with placebo as an adjuvant to antibiotic therapy in the treatment of acute exudative pharyngitis.\n The study was a randomized, doubled-blind, placebo-controlled, single-center, parallel, outpatient clinical trial. After consent was obtained, each patient was asked to rate his or her pain on a 10-cm numbered visual analog scale (VAS; 0-10). All of the patients received injectable benzathine penicillin. If allergic to penicillin, they were started on a 10-day course of polyenteric-coated erythromycin (PCE). Each patient was randomized to receive either i.m. betamethasone or i.m. placebo. All patients were contacted by telephone at 24 and 48 hours by one of the study investigators and asked to rate their pain based on another VAS. If their pain was not resolved by 48 hours, they were called again daily between the third and seventh days after the initial visit to determine the time of pain resolution.\n A total of 92 patients were enrolled in the study, with 46 randomized to receive placebo and 46 to receive betamethasone. Eight patients were excluded from the statistical analysis because of inability to obtain follow-up. Demographic comparison showed that gender distributions, ages, mean initial pain scores, mean times to the first and second follow-up calls, and treatment regimens were similar in the 2 groups. There were significantly better pain scores for the betamethasone group at first follow-up (p = 0.0005), at second follow-up (p = 0.004), and in number of hours until relief of pain (p = 0.004). When only those patients with a positive culture for a streptococcus species were analyzed, there also were significant reductions in pain score at the first (p = 0.006) and second (p = 0.02) follow-up visits.\n Pain relief was greater and more rapid in patients treated with betamethasone as an adjuvant therapy in acute exudative pharyngitis.", "Acute pharyngitis is a frequent and well-documented complaint in general practice but the associated suffering has remained largely unaddressed in the literature. Evidence, however, from five randomised controlled trials suggests that corticosteroids may be useful in relieving pain and discomfort arising from the condition.\n To determine if short-acting oral therapy with prednisone was more effective than placebo in alleviating the suffering from acute pharyngitis in adults in a general practice setting.\n Randomised placebo-controlled trial.\n General practice in Israel.\n Patients with acute pharyngitis were randomised to receive 60 mg prednisone orally for 1 or 2 days, or identical placebo treatment. The main outcome measures were throat pain, measured by a visual analogue scale at 12, 24, 48 and 72 hours after presentation, time off work, fever, dysphagia, recurrence of symptoms and bacterial recurrence.\n Patients treated with prednisone experienced more rapid throat pain resolution than those in the placebo group. No adverse effects were reported nor any differences between the two groups regarding either symptom or positive bacterial culture recurrence.\n Short-acting oral steroid therapy is effective for shortening throat pain duration in acute pharyngitis.", "To determine the efficacy of dexamethasone as adjuvant therapy to improve pain relief in patients with severe, acute exudative pharyngitis.\n Prospective, randomized, double-blinded, placebo-controlled clinical trial.\n Large, urban community hospital emergency department with an emergency medicine residency program.\n Patients aged 12 to 65 years old with exudative pharyngitis and severe dysphagia/odynophagia. Patients with cancer, AIDS, diabetes mellitus, recent steroid use, pregnancy, or suspicion of peritonsillar abscess were excluded.\n All patients received oral penicillin (500 mg Pen VK) or erythromycin (333 mg base) three times daily for ten days in addition to either 10 mg single-dose dexamethasone or saline placebo IM injection.\n Fifty-eight patients graded their initial degree of throat pain on a visual-analog scale that was 15 cm long and scored from 0 to 3.0 in 0.5-cm increments. Follow-up was obtained on 51 patients to determine their condition at 24 hours. At entry, there was no difference in age, weight, antibiotic assignment, or initial pain score between groups. Improvement in pain score (initial versus 24 hours) was 1.8 +/- 0.8 in the 26 patients of the dexamethasone group and 1.2 +/- 0.9 in the 25 patients of the placebo group (P < .05). Time to onset of pain relief was also faster in steroid-treated patients who demonstrated relief beginning at 6.3 +/- 5.3 hours, compared with 12.4 +/- 8.5 hours in the placebo group (P < .01). Of the 26 patients evaluated at seven days (13 in each group), time to complete lack of pain averaged 15.0 +/- 11.4 hours in the dexamethasone group and 35.4 +/- 17.9 hours in the placebo group (P < .02). Complications attributable to dexamethasone were not observed.\n In patients with severe, acute exudative pharyngitis, single-injection dexamethasone adjuvant compared with placebo resulted in statistically and clinically significant improvement, as evidenced by more rapid onset and greater degree of pain relief." ]

[ "12418582", "16675212", "17362472", "18455221", "17845589", "15006018", "20874458" ]

[ "Evaluation of different inhaled combination therapies (EDICT): a randomised, double-blind comparison of Seretide (50/250 microg bd Diskus vs. formoterol (12 microg bd) and budesonide (800 microg bd) given concurrently (both via Turbuhaler) in patients with moderate-to-severe asthma.", "EXCEL: A randomised trial comparing salmeterol/fluticasone propionate and formoterol/budesonide combinations in adults with persistent asthma.", "Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations.", "Comparison of adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler and fixed-dose fluticasone propionate/salmeterol dry powder inhaler in asthma patients.", "Beclomethasone/formoterol vs fluticasone/salmeterol inhaled combination in moderate to severe asthma.", "Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma.", "Long-term safety of mometasone furoate/formoterol combination for treatment of patients with persistent asthma." ]

[ "The aim of this study was to compare the efficacy safety and cost of Seretide (salmeterol/fluticasone propionate (Salm/FP), 50/250 microg bd) via Diskus with formoterol (Form; 12 microg bd) and budesonide (Bud; 800 microg bd) given concurrently (Form+Bud) via Turbuhaler in patients with moderate-to-severe asthma who were uncontrolled on existing corticosteroid therapy. The study used a randomised, double-blind, double-dummy, parallel-group design, consisting of a 2-week run-in period on current corticosteroid therapy (1000-1600 microg/day of BDP or equivalent) and a 12-week treatment period. Symptomatic patients (n = 428) with FEV1 of 50-85% predicted and increased symptom scores or reliever use during run-in were randomly allocated to receive either Salm/FP (50/250 microg bd) via a single Diskus inhaleror Form+Bud (12+800 microg bd) via separate Turbuhalers. Clinic, diary card and asthma-related health-care resource utilisation data were collected. Improvement in mean morning peak expiratory flow (PEFam was similar in the Salm/FP and Form+Bud groups. Both PEFam and mean evening PEF (PEFpm) increased by a clinically significant amount (>20 L/min) from baseline in both treatment groups. The mean rate of exacerbations (mild, moderate or severe) was significantly lower in the Salm/FP group (0.472) compared with the Form+Bud group (0.735) (ratio = 0.64; P < 0.001), despite the three-fold lower microgram inhaled corticosteroid dose in the Salm/FP group. Patients in the Salm/FP group also experienced significantly fewer nocturnal symptoms, with a higher median percentage of symptom-free nights (P = 0.04), nights with a symptom score <2 (P = 0.03), and nights with no awakenings (P = 0.02). Total asthma-related health-care costs were significantly lower in the Salm/FP group than the Form+Bud group (P<0.05). Both treatments were well tolerated, with a similar low incidence of adverse events. This study showed that in symptomatic patients with moderate-to-severe asthma, Salm/FP (50/250 microg bd), administered in a single convenient device (Diskus), was at least as effective as an approximately three-fold higher microgram corticosteroid dose of Bud (800 microg bd) given concurrently with Form (12 microg bd) in terms of improvement in PEFam, and superior at reducing exacerbations and nights with symptoms or night-time awakenings. Salm/FP was also the less costly treatment due primarily to lower hospitalisation and drug costs.", "This multicentre, parallel group, double-blind, double-dummy, randomised 24-week study was designed to compare the efficacy of salmeterol/fluticasone propionate combination (SFC) 50/250 microg one inhalation twice daily (bid) with formoterol/budesonide combination (FBC) 6/200 microg two inhalations bid in patients with persistent asthma, currently receiving 1000-2000 microg/day of inhaled corticosteroids.\n The intent-to-treat population comprised 694 patients in the SFC group and 697 patients in the FBC group.\n The primary endpoint, mean rate of all exacerbations over 24 weeks, was similar in both treatment groups (SFC: 2.69; FBC: 2.79; SFC/FBC ratio 0.96; 95% CL 0.84, 1.10; P=0.571). A reduction in the rate of exacerbations over time was observed in both treatment groups. Overall, there was a 30% lower annual rate of moderate/severe exacerbations in the SFC group compared with the FBC group (95% CI 0-49%, 52% reduction vs. 1% increase; P=0.059). This effect increased with time: in weeks 17-24 the moderate/severe exacerbation rate was 57% lower in the SFC group compared with the FBC group (95% CI 21-77% reduction; P=0.006). Similar improvements in lung function, asthma symptoms and rescue medication usage were seen with both treatments and both were well tolerated.\n Twice-daily treatment with SFC and FBC over 6 months significantly improved asthma symptoms and lung function in patients with persistent asthma. The rate of exacerbations was significantly reduced over time on both treatments but SFC was found to be significantly superior to FBC in reducing the rate of moderate/severe exacerbations with sustained treatment.", "This randomised, double-blind, 6-month study compared budesonide/formoterol for maintenance and relief with salmeterol/fluticasone and a fixed maintenance dose of budesonide/formoterol, both with terbutaline for relief. Following a 2-week run-in, 3335 symptomatic adults and adolescents (mean FEV1 73% predicted, mean inhaled corticosteroid dose 745 microg/day) received budesonide/formoterol 160/4.5 microg one inhalation bid plus additional inhalations as needed, salmeterol/fluticasone 25/125 microg two inhalations bid plus as-needed terbutaline or budesonide/formoterol 320/9 microg one inhalation bid plus as-needed terbutaline. Budesonide/formoterol for maintenance and relief prolonged the time to first severe exacerbation requiring hospitalisation, emergency room treatment or oral steroids (primary variable) vs. fixed-dose salmeterol/fluticasone and budesonide/formoterol (p=0.0034 and p=0.023 respectively; log-rank test). Exacerbation rates were 19, 16 and 12 events/100 patients/6 months for salmeterol/fluticasone, fixed-dose budesonide/formoterol and budesonide/formoterol for maintenance and relief, respectively, [rate reduction vs. fixed-dose salmeterol/fluticasone (0.61; 95% CI 0.49-0.76, p<0.001) and vs. fixed-dose budesonide/formoterol (0.72; 95% CI 0.57-0.90, p=0.0048)]. Budesonide/formoterol maintenance and relief patients used less inhaled corticosteroid vs. salmeterol/fluticasone and fixed-dose budesonide/formoterol patients. All treatments provided similar marked improvements in lung function, asthma control days and asthma-related quality of life. Budesonide/formoterol for maintenance and relief reduces asthma exacerbations and maintains similar daily asthma control at a lower overall drug load compared with fixed-dose salmeterol/fluticasone and budesonide/formoterol.", "The adjustable-dose budesonide/formoterol dry powder inhaler (DPI) has demonstrated similar or greater asthma control with less inhaled corticosteroid compared with the fixed-dose budesonide/formoterol DPI.\n We sought to evaluate the efficacy, tolerability, and resource use of maintenance therapy with the adjustable-dose budesonide/formoterol pressurized metered-dose inhaler versus the fixed-dose budesonide/formoterol pressurized metered-dose inhaler and the fixed-dose fluticasone propionate/salmeterol DPI.\n This was a randomized, open-label, multicenter study of patients (N = 1225) 12 years and older with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose budesonide/formoterol (160/4.5 microg x 2 inhalations [320/9 microg] twice daily) or fixed-dose fluticasone propionate/salmeterol (250/50 microg x 1 inhalation twice daily) for 1 month (treatment period 1), after which, the fixed-dose fluticasone propionate/salmeterol group continued therapy and the fixed-dose budesonide/formoterol group was randomized 1:1 to fixed-dose budesonide/formoterol or adjustable-dose budesonide/formoterol (adjustable from 2 inhalations [320/9 microg] twice daily to 2 inhalations [320/9 microg] once daily or 4 inhalations [640/18 microg] twice daily) for 6 months (treatment period 2).\n There were no significant between-group differences in asthma exacerbations (primary variable), asthma symptoms, or lung function during the 7-month treatment period. Less study drug (inhalations per day, P < .001) was used with adjustable-dose versus fixed-dose budesonide/formoterol. All treatments were well tolerated.\n Adjustable-dose and fixed-dose budesonide/formoterol showed no differences in asthma control or tolerability versus fixed-dose fluticasone propionate/salmeterol.", "Recommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long-acting beta(2)-agonist. The present study was designed to compare a new fixed combination of extrafine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol.\n This was a phase III, multinational, multicentre, double-blind, randomized, two-arm parallel groups, controlled study. After a 2-week run-in period, 228 patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 microg plus formoterol 6 microg or fluticasone 125 microg plus salmeterol 25 microg, both delivered two inhalations b.i.d. via a pressurized metered dose inhaler.\n The analysis of noninferiority on the primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups (difference -3.32 l/min; 95% CI -17.92 to 11.28). A significant improvement from baseline in lung function, symptom score and rescue medication use was observed in both groups at all time points. Beclomethasone plus formoterol combination showed a significantly faster onset of bronchodilation when compared with fluticasone plus salmeterol with the difference maintained for up to 1 h postdosing. No differences were observed between treatments in the rate of asthma exacerbations, frequency of adverse events and overnight urinary cortisol/creatinine ratio.\n The new combination of extrafine beclomethasone plus formoterol is not inferior to the marketed combination of fluticasone and salmeterol in terms of efficacy and tolerability, with the advantage of a faster onset of bronchodilation. ( ClinicalTrials.gov number, NCT00394368).", "Current asthma guidelines recommend that patients are educated to adjust their medication according to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication according to asthma symptoms.\n This study examined whether asthma control improved if patients adjusted the maintenance dose of budesonide/formoterol (Symbicort Turbuhaler* 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens.\n Symptomatic patients with asthma (n = 658, mean symptom score 1.5, mean inhaled corticosteroids 735 microg/day, mean forced expiratory volume in 1 second [FEV(1)] 84% predicted) were randomised after 2 weeks' run-in to either: budesonide/formoterol adjustable maintenance dosing (AMD), budesonide/formoterol FD or salmeterol/fluticasone (Seretide Diskus dagger 50/250 microg) FD. In a 4-week double-blind period, both budesonide/formoterol AMD and FD groups received two inhalations twice daily (bid) and salmeterol/fluticasone FD patients received one inhalation bid. In the following 6-month open extension, both FD groups continued with the same treatment. Patients in the AMD group with well-controlled asthma stepped down to one inhalation bid; others continued with two inhalations bid. All AMD patients could increase to four inhalations bid for 7-14 days if symptoms worsened. All patients used terbutaline or salbutamol for symptom relief throughout. The primary variable was the odds of achieving a well-controlled asthma week (WCAW).\n The odds ratio for achieving a WCAW did not differ between the FD regimens; however, during the open period, budesonide/formoterol AMD increased the odds of achieving a WCAW vs. budesonide/formoterol FD (odds ratio 1.335; 95% CI: 1.001, 1.783; p = 0.049) despite a 15% reduction in average study drug use. Budesonide/formoterol AMD patients had a lower exacerbation rate over the study: 40% lower vs. salmeterol/fluticasone FD (p = 0.018); 32% lower vs. budesonide/formoterol FD (NS). During the double-blind period, there were no clinically relevant differences between the budesonide/formoterol FD and salmeterol/fluticasone FD groups. Budesonide/formoterol AMD patients used less reliever medication in the open extension: 0.58 vs. 0.92 occasions/day for budesonide/formoterol FD (p = 0.001) and 0.80 occasions/day for salmeterol/fluticasone FD (p = 0.011).\n Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control by reducing exacerbations and reliever medication usage compared with fixed-dose salmeterol/fluticasone.", "The combination of inhaled corticosteroid (ICS) and long-acting β₂-agonist is recommended for treatment of patients with persistent asthma inadequately controlled on ICS monotherapy. This study was conducted to evaluate the long-term safety of mometasone furoate/formoterol (MF/F) administered through metered-dose inhaler (MDI) in patients with persistent asthma previously on medium- to high-dose ICS.\n This was a 52-week, randomized, multicenter, parallel-group, open-label, evaluator-blinded study. At baseline, 404 patients (aged ≥12 years) were stratified according to their previous ICS dose (medium or high), then randomized 2:1 to receive twice-daily treatment of MF/F (200/10 or 400/10 μg) or fluticasone propionate/salmeterol (FP/S; 250/50 or 500/50 μg). The primary endpoint was the number and percentage of patients reporting any adverse event (AE). Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC(0-24 h)) and ocular changes. Pulmonary function, asthma symptoms, and use of rescue medication were monitored.\n The incidence of ≥1 treatment-emergent AE was similar across treatment groups (MF/F 200/10 μg, 77.3% [n= 109]; FP/S 250/50 μg, 82.4% [n= 56]; MF/F 400/10 μg, 79.2% [n= 103]; FP/S 500/50 μg, 76.9% [n= 50]). Rates of treatment-related AEs were also similar across treatment groups (MF/F 200/10 μg, 28.4%; FP/S 250/50 μg, 23.5%; MF/F 400/10 μg, 23.1%; FP/S 500/50 μg, 20.0%). Headache (3.7%) and dysphonia (2.7%) were the most common treatment-related AEs overall. The nature and frequency of AEs and the decreases in plasma cortisol AUC(0-24 h) observed with MF/F treatment were similar to those observed with FP/S treatment. Ocular events were rare (2-6% overall incidence among treatment groups); in particular, no posterior subcapsular cataracts were reported. Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MF/F 400/10 μg group; one for reduced visual acuity in the FP/S 250/50 μg group) and no asthma-related deaths occurred. Furthermore, MF/F showed numerical improvement in lung function and clinical benefits by reducing asthma symptoms and rescue medication use.\n One-year treatment with the new combination therapies - twice-daily MF/F-MDI 200/10 and 400/10 μg - is safe and well tolerated in patients with persistent asthma." ]

[ "16051891" ]

[ "Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial." ]

[ "Cerebral vasospasm remains a major source of morbidity after aneurysmal subarachnoid hemorrhage (SAH). We demonstrate that simvastatin reduces serum markers of brain injury and attenuates vasospasm after SAH.\n Patients with angiographically documented aneurysmal SAH were randomized within 48 hours of symptom onset to receive either simvastatin (80 mg daily; n=19) or placebo (n=20) for 14 days. Plasma alanine aminotransferase, aspartate aminotransferase, and creatine phosphokinase were recorded weekly to evaluate laboratory evidence of hepatitis or myositis. Serum markers of brain injury were recorded daily. The primary end point of vasospasm was defined as clinical impression (delayed ischemic deficit not associated with rebleed, infection, or hydrocephalus) in the presence of > or =1 confirmatory radiographic test (angiography or transcranial Doppler demonstrating mean V(MCA) >160 m/sec).\n There were no significant differences in laboratory-defined transaminitis or myositis between groups. No patients developed clinical symptoms of myopathy or hepatitis. Plasma von Willebrand factor and S100beta were decreased 3 to 10 days after SAH (P<0.05) in patients receiving simvastatin versus placebo. Highest mean middle cerebral artery transcranial Doppler velocities were significantly lower in the simvastatin-treated group (103+/-41 versus 149+/-47; P<0.01). In addition, vasospasm was significantly reduced (P<0.05) in the simvastatin-treated group (5 of 19) compared with those who received placebo (12 of 20).\n The use of simvastatin as prophylaxis against delayed cerebral ischemia after aneurysmal SAH is a safe and well-tolerated intervention. Its use attenuates serum markers associated with brain injury and decreases the incidence of radiographic vasospasm and delayed ischemic deficit." ]

[ "8873539", "15891317", "12596619", "9054252", "3017039", "10519497", "7879930", "7978438", "3605732", "3942335", "15277909", "16243997", "8868976", "15189665", "8831304", "10594409", "14579210", "7980723", "10735784", "12006795", "1932647", "11878517", "8400091", "10195508", "9054253", "8431573", "10212709", "11004033", "16202898" ]

[ "Small, oral dose of clonidine reduces the incidence of intraoperative myocardial ischemia in patients having vascular surgery.", "Dexmedetomidine does not improve patient satisfaction when compared with propofol during mechanical ventilation.", "Oral clonidine reduces myocardial ischemia in patients with coronary artery disease undergoing noncardiac surgery.", "Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting.", "Clonidine and the sympatico-adrenal response to coronary artery by-pass surgery.", "Effect of mivazerol on perioperative cardiac complications during non-cardiac surgery in patients with coronary heart disease: the European Mivazerol Trial (EMIT).", "Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group.", "Premedication with oral and transdermal clonidine provides safe and efficacious postoperative sympatholysis.", "Anesthesia and hypertension: the effect of clonidine on perioperative hemodynamics and isoflurane requirements.", "Effects of clonidine on narcotic requirements and hemodynamic response during induction of fentanyl anesthesia and endotracheal intubation.", "Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery.", "Clonidine premedication in patients with sleep apnea syndrome: a randomized, double-blind, placebo-controlled study.", "Can clonidine, enoximone, and enalaprilat help to protect the myocardium against ischaemia in cardiac surgery?", "The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit.", "Clonidine for major vascular surgery in hypertensive patients: a double-blind, controlled, randomized study.", "Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit.", "ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based versus propofol-based sedation regimens.", "Effect of clonidine on myocardial ischaemia: a double-blind pilot trial.", "The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery.", "Bispectral index-guided sedation with dexmedetomidine in intensive care: a prospective, randomized, double blind, placebo-controlled phase II study.", "Effects of clonidine on variation of arterial blood pressure and heart rate during carotid artery surgery.", "Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions.", "Clonidine improves perioperative myocardial ischemia, reduces anesthetic requirement, and alters hemodynamic parameters in patients undergoing coronary artery bypass surgery.", "High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting.", "Perioperative sympatholysis. Beneficial effects of the alpha 2-adrenoceptor agonist mivazerol on hemodynamic stability and myocardial ischemia. McSPI--Europe Research Group.", "Clonidine premedication for coronary artery bypass grafting under high-dose alfentanil anesthesia: intraoperative and postoperative hemodynamic study.", "Clonidine and cardiac surgery: haemodynamic and metabolic effects, myocardial ischaemia and recovery.", "The effect of clonidine premedication on hemodynamic responses to microlaryngoscopy and rigid bronchoscopy.", "A prospective, double-blind, randomized, placebo-controlled study of dexmedetomidine as an adjunct to epidural analgesia after thoracic surgery." ]

[ "Most new perioperative myocardial ischemic episodes occur in the absence of hypertension or tachycardia. The ability of alpha 2-adrenoceptor agonists to inhibit central sympathetic outflow may benefit patients with coronary artery disease by increasing the myocardial oxygen supply and -demand ratio.\n A randomized double-blind study design was used in 297 patients scheduled to have elective vascular surgical procedures to evaluate the effects of 2 micrograms/kg-1 oral clonidine (n = 145) or placebo (n = 152) on the incidence of perioperative myocardial ischemic episodes, myocardial infarction, and cardiac death. Continuous real-time S-T segment trend analysis (lead II and V5) was performed during anesthesia and surgery and correlated with arterial blood pressure and heart rate before and during ischemic events. Dose requirements for vasoactive and antiischemic drugs to control blood pressure and heart rate as well as episodes of myocardial ischemia (i.e., catecholamines, beta-adrenoceptor antagonists, nitrates, and systemic vasodilators) and fluid volume load were recorded.\n Administration of clonidine reduced the incidence of perioperative myocardial ischemic episodes from 39% (59 of 152) to 24% (35 of 145) (P < 0.01). Hemodynamic patterns, percentage of ischemic time, and the number of ischemic episodes per patient did not differ. Nonfatal myocardial infarction developed after operation in four patients receiving placebo compared with none receiving clonidine (day 2 to 21; P = 0.07). The incidence of fatal cardiac events (1 vs. 2) was not different. Dose requirements for vasoactive and antiischemic drugs did not differ between the groups, but the amount of presurgical fluid volume was slightly greater in patients receiving clonidine (951 +/- 388 vs. 867 +/- 381 ml; P < 0.03).\n A small oral dose of clonidine, given prophylactically, can reduce the incidence of perioperative myocardial ischemic episodes without affecting hemodynamic stability in patients with suspected or documented coronary artery disease.", "Dexmedetomidine (DEX) may provide a sedation level that enables sleep and communication, with less amnesia and pain medication requirements, during mechanical ventilation. Our study directly assessed patient-perceived satisfaction with coronary artery bypass graft surgery after administration of DEX or propofol for intensive care unit (ICU) sedation.\n Prospective, randomized clinical study with subsequent questionnaire administration.\n Tertiary care surgical ICU.\n A total of 89 adult, nonemergent, coronary artery bypass graft patients with an expected length of intubation of <24 hrs.\n Patients were randomized to either DEX or propofol; drug administration was performed via standardized anesthesia and nursing protocols.\n Patients reported perceptions of their ICU experience after mechanical ventilation with a modified numerical-scale Hewitt questionnaire, validated specifically for ICU patients. Patients were questioned regarding awareness, recall, generalized comfort, level of pain, ability to interact with healthcare providers and family, feelings of agitation and anxiety, perceived ease of extubation, ability to sleep or rest, and satisfaction with ICU experience.\n Groups were well matched at baseline, with a mean +/- sd age of 63.0 +/- 10.4 yrs and weight of 88.7 +/- 16.7 kg. No difference was observed for length of surgery, length of intubation, or ICU stay (p > .05). DEX patients perceived a shorter length of intubation (p = .044). A deeper sedation level was found in the propofol group (p = .021), with similar morphine and midazolam requirements (p = .317). Patient-rated level of overall awareness as a marker of amnesia did not differ between groups (p = .653). The ability to rest or sleep trended toward significance favoring propofol (p = .051). On evaluation of questionnaire ratings, DEX patients expressed more discomfort (p = .046), pain (p = .096), and sleeping difficulty (p = .036). Similar comfort levels were reported during extubation (p = .179).\n Despite theoretical advantages of DEX to improve overall patient satisfaction, the two agents provide similar responses to amnesia and pain control. According to our findings, DEX does not seem to have any advantage compared with propofol for short-term sedation after coronary artery bypass graft surgery.", "To access the clinical effect of clonidine on reduction of myocardial ischemia events in patients with history of coronary artery disease undergoing noncardiac surgeries.\n Sixty ASA class III patients with coronary artery disease were allotted at random to two groups in a prospective, double-blind study to receive either clonidine (3 micrograms/kg) or placebo (control group) 90 minutes before arrival at the operating room. Continuous EKG monitoring (Holter monitor) was performed to analyze the ST segment in lead II, V2 and V5 during the preoperative (since late hours the night before operation), intraoperative and early postoperative periods (total monitoring time = 24 hours). The episode of myocardial ischemia defined as the magnitude of ST segment depression of at least 1 mm, occurring 60 ms after the J point and persisting for three minutes or more was recorded. Perioperative hemodynamic data were analyzed with two-way ANOVA with repeated measures. Student's t-test for unpaired data was used for analysis of demographics. Chi-square test was used for ST segment changes. Results are expressed as mean +/- SD and P < 0.05 was considered to be statistically significant.\n In the control group, 9 patients (30%) were noted to have episodes of ischemia preoperatively, 7 patients (23.3%) intraoperatively, and 12 patients (40%) postoperatively. The occurrence of myocardial ischemia peaked in the early postoperative period (P < 0.05). On the contrary, in the clonidine group, 10 patients (33.3%) saw ischemic episodes preoperatively, 3 patients (10%) intraoperatively and 5 patients (16.7%) postoperatively. The incidence of myocardial ischemia in clonidine group was significantly lower than that in placebo group in intraoperative and postoperative periods. The mean arterial pressure was significantly lower in some clonidine-treated patients during perioperative periods (P < 0.05). A number of patients in clonidine group suffered from drowsiness (66.7%) after operation (P < 0.05), but they could be easily aroused. In regard to dryness of mouth, nausea and vomiting clonidine and control groups did not differ much (P > 0.05). Demerol consumption was significantly lower in clonidine group (43.7 +/- 4.6 mg) than in control group (76.3 +/- 3.7 mg, P < 0.05).\n We conclude that premedication with oral clonidine can significantly reduce the incidence of perioperative myocardial ischemia in patients with CAD undergoing noncardiac surgeries. The incidence of myocardial ischemia in these patients is rather high during perioperative period, which deserves our exceptional caution.", "Alpha 2-adrenergic agonists decrease sympathetic tone with ensuing attenuation of neuroendocrine and hemodynamic responses to anesthesia and surgery. The effects of dexmedetomidine, a highly specific alpha 2-adrenergic agonist, on these responses have not been reported in patients undergoing coronary artery bypass grafting.\n Eighty patients scheduled for elective coronary artery bypass grafting received, in a double-blind manner, either a saline placebo or a dexmedetomidine infusion, initially 50 ng.kg-1.min-1 for 30 min before induction of anesthesia with fentanyl, and then 7 ng.kg-1.min-1 unit the end of surgery. Filling pressures, blood pressure, and heart rate were controlled by intravenous fluid and by supplemental anesthetics and vasoactive drugs.\n Compared with placebo, dexmedetomidine decreased plasma norepinephrine concentrations by 90%, attenuated the increase of blood pressure during anesthesia (3 vs. 24 mmHg) and surgery (2 vs. 14 mmHg), but increased slightly the need for intravenous fluid challenge (29 vs. 20 patients) and induced more hypotension during cardiopulmonary bypass (9 vs. 0 patients). Dexmedetomidine decreased the incidence of intraoperative (2 vs. 13 patients) and postoperative (5 vs. 16 patients) tachycardia. Dexmedetomidine also decreased the need for additional doses of fentanyl (3.1 vs. 5.4), the increments of enflurane (4.4 vs. 5.6), the need for beta blockers (3 vs. 11 patients), and the incidence of fentanyl-induced muscle rigidity (15 vs. 33 patients) and postoperative shivering (13 vs. 23 patients).\n Intraoperative intravenous infusion of dexmedetomidine to patients undergoing coronary artery revascularization decreased intraoperative sympathetic tone and attenuated hyperdynamic responses to anesthesia and surgery but increased the propensity toward hypotension.", "Clonidine was administered intravenously in an attempt to limit sympatico-adrenal activity and thereby reduce the incidence of arterial hypertension associated with coronary artery by-pass graft surgery (CABG). Forty patients scheduled for CABG were assigned to two groups. Twenty patients received clonidine 4 micrograms kg-1 before surgery, 2 micrograms kg-1 after cardiopulmonary by-pass and 1 microgram kg-1 when the skin was sutured. The other 20 patients served as controls. All patients were anesthetized with fentanyl, droperidol, nitrous oxide and alcuronium. During surgery 5 min after sternotomy, mean arterial pressure was 13 mmHg lower (P less than 0.01) in the clonidine group, while after operation the difference between the groups was negligible. Both during and after surgery the plasma catecholamine concentrations were significantly lower in the clonidine group (P less than 0.01). The greatest difference between the groups was seen 90 min after operation, when plasma noradrenaline and plasma adrenaline concentrations in the clonidine group were less than 1/3 of those in the control group (P less than 0.01). As judged by catecholamine concentrations clonidine was effective in attenuating sympatico-adrenal hyperactivity during and after surgery. Postoperative arterial hypertension was not reduced, however, and it is concluded that other factors besides sympatico-adrenal hyperactivity must be important.", "Mivazerol is a drug with alpha2-agonist properties that reduces post-ganglionic noradrenaline availability and spinal efferent sympathetic output.\n A double-blind randomized placebo-controlled trial was conducted in 61 European centers during a 2.5-yr period on 2,854 patients: 1,897 with coronary heart disease and 957 patients without overt coronary heart disease but classified as at high risk for it. The present analysis was restricted to those patients with previous known coronary heart disease of whom 48% had vascular surgery, 32% non-vascular thoracic or abdominal surgery, and 20% orthopedic surgery. Mivazerol or placebo were given intravenously from the induction of anesthesia for up to 72 h.\n In the 1,897 patients with established coronary heart disease, mivazerol did not reduce the primary endpoint--the combination of myocardial infarction or death--or all-cause deaths significantly. A preplanned subgroup analysis of 904 patients with known coronary heart disease undergoing vascular surgery showed that there were fewer primary endpoints in those receiving mivazerol (risk ratio [RR], 0.67; 95% CL, 0.45-0.98; P = 0.037) and fewer cardiac deaths (6 of 454 vs. 18 of 450: RR, 0.33; 95% confidence limits, 0.13-0.82; P = 0.017). The all-cause death rate was also decreased (RR, 0.41; 95% CL, 0.18-0.91; P = 0.024), although there was no significant reduction in myocardial infarction.\n The alpha2-adrenergic agonist, mivazerol, did not alter the rates of myocardial infarction or cardiac death in patients with known coronary heart disease undergoing noncardiac surgery. However, it may have protected patients undergoing vascular surgery from further coronary events, and a specific study of such patients is now indicated.", "Dexmedetomidine, a highly selective alpha 2-adrenergic agonist, increases perioperative hemodynamic stability in healthy patients but decreases blood pressure and heart rate. The goal of this study was to evaluate, in a preliminary manner, the hemodynamic effects of perioperatively administered dexmedetomidine in surgical patients at high risk for coronary artery disease.\n Twenty-four vascular surgery patients received a continuous infusion of placebo or one of three doses of dexmedetomidine, targeting plasma concentrations of 0.15 ng/ml (low dose), 0.30 ng/ml (medium dose), or 0.45 ng/ml (high dose) from 1 h before induction of anesthesia until 48 h postoperatively. All patients received standardized anesthesia and hemodynamic management. Blood pressure, heart rate, and Holter ECG were monitored; additional monitoring included continuous 12-lead ECG preoperatively, anesthetic concentrations and myocardial wall motion (echocardiography) intraoperatively, and cardiac enzymes postoperatively.\n Preoperatively, there was a decrease in heart rate (low dose 11%, medium dose 5%, high dose 20%) and systolic blood pressure (low dose 3%, medium dose 12%, high dose 20%) in patients receiving dexmedetomidine. Intraoperatively, dexmedetomidine groups required more vasoactive medications to maintain hemodynamics within predetermined limits. Postoperatively, demedetomidine groups had less tachycardia (minutes/monitored hours) than the placebo group (placebo 23 min/h; low dose 9 min/h, P = 0.006; medium dose 0.5 min/h, P = 0.004; high dose 2.3 min/h, P = 0.004). Bradycardia was rare in all groups. There were no myocardial infarctions or discernible trends in the laboratory results.\n Infusion of dexmedetomidine up to a targeted plasma concentration of 0.45 ng/ml appears to benefit perioperative hemodynamic management of surgical patients undergoing vascular surgery but required greater intraoperative pharmacologic intervention to support blood pressure and heart rate.", "We studied 61 patients undergoing elective major non-cardiac surgery in a randomized, double-blind, placebo-control clinical trial to test the hypothesis that the addition of clonidine to a standardized general anesthetic could safely provide postoperative sympatholysis for patients with known or suspected coronary artery disease. Patients were allocated randomly to receive either placebo (n = 31) or clonidine (n = 30). The treatment group received premedication with a transdermal clonidine system (0.2 mg/d) the night prior to surgery, which was left in place for 72 h, and 0.3 mg oral clonidine 60-90 min before surgery. Clonidine reduced enflurane requirements, intraoperative tachycardia, and myocardial ischemia (1/28 clonidine patients vs 5/24 placebo, P = 0.05). However, clonidine decreased heart rates only during the first five postoperative hours; the incidence of postoperative myocardial ischemia (6/28 clonidine vs 5/26 placebo) did not differ between the two groups. Patients who experienced postoperative myocardial ischemia tended to have higher heart rates after surgery. Clonidine significantly reduced the plasma levels of epinephrine (P = 0.009) and norepinephrine (P = 0.026) measured on the first postoperative morning. There were no differences in the need for intravenous fluid therapy or antihypertensive therapy after surgery. The number of hours spent in an intensive care setting and the number of days spent in hospital were not different between the two groups. These results suggest that larger doses of clonidine should be investigated for their ability to decrease postoperative tachycardia and myocardial ischemia.", "Thirty patients (ASA physical status II-III) with a history of arterial hypertension, whose blood pressure (BP) control varied from normotension to moderate hypertension (diastolic BP less than 110 mmHg), scheduled for elective surgery under general anesthesia, were randomly assigned to two groups. Group 1 was premedicated 90-120 min prior to induction with diazepam 0.15 mg X kg-1 po; group 2, in addition, received clonidine 5 micrograms X kg-1 po. Anesthetic depth was assessed by on-line aperiodic analysis of the electroencephalogram. Following lidocaine 1 mg X kg-1 and fentanyl 2 micrograms X kg-1 (group 1 only), anesthesia was induced with thiopental 3-4 mg X kg-1 and vecuronium 0.1 mg X kg-1 was used to facilitate endotracheal intubation. Anesthesia was maintained with isoflurane in N2O/O2 and supplemented by fentanyl. In group 2, clonidine produced a rapid preoperative control of systolic and diastolic BP from 166 +/- 32/95 +/- 14 to 136 +/- 80 +/- 11 (P less than 0.01), was more effective in blunting the reflex tachycardia associated with laryngoscopy and endotracheal intubation than lidocaine-fentanyl pretreatment. It significantly reduced the intraoperative lability (coefficient of variation) of systolic (P less than 0.01) and diastolic BP and heart rate (HR) (P less than 0.05), and resulted in significantly slower HR during recovery (P less than 0.01). Anesthetic requirements for isoflurane were reduced 40% (P less than 0.01) in group 2; narcotic supplementation was also significantly reduced (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)", "The effects of clonidine, a centrally acting alpha 2-adrenergic receptor agonist, on depth of fentanyl anesthesia and on cardiovascular response to laryngoscopy and intubation were studied. Twenty-four patients undergoing aortocoronary bypass surgery (ACBS) with a history of arterial hypertension, coronary artery disease (NYHA class 3-4), and well-preserved left ventricular function were assigned randomly to either Group 1 (n = 12), who received standard premedication, or Group 2 (n = 12), who received clonidine 5 micrograms X kg-1 po in addition to standard premedication 90 min before estimated induction time. Depth of anesthesia was assessed by on-line aperiodic computerized analysis of the electroencephalogram (Lifescan EEG Monitor). Fentanyl was administered in 250-micrograms increments to shift the EEG to the 0.5-3-Hz frequency range (delta activity) in all subjects. In both groups, the anesthetic regimen effectively prevented hyperdynamic cardiovascular responses to laryngoscopy and intubation. No significant differences in measured or derived hemodynamic variables were observed between the two groups during the awake control period, except for stroke volume index (SVI), which was significantly greater in Group 1, 44 +/- 9 ml X beat-1 X m-2 compared with Group 2, 35 +/- 3.3 ml X beat-1 X m-2 (P less than 0.05). By contrast, fentanyl requirements in Group 2 were significantly reduced by 45% when compared with Group 1, i.e., from 110 +/- 23 to 61 +/- 19 micrograms X kg-1 (P less than 0.001). The authors conclude that at a similar anesthetic depth, as assessed by the EEG shift into the lower frequency range (0.5-3 Hz), a markedly reduced fentanyl dose effectively prevented the hyperdynamic cardiovascular response to laryngoscopy and intubation in the group of patients premedicated with clonidine. This is likely explained by the known synergistic inhibitory action of opiates and alpha 2-adrenoceptor agonists on central sympathetic outflow.", "Perioperative myocardial ischemia occurs in 20-40% of patients at risk for cardiac morbidity and is associated with a ninefold increase in risk of cardiac morbidity.\n In a prospective, double-blinded, clinical trial, we studied 190 patients with or at risk for coronary artery disease in two study groups with a 2:1 ratio (clonidine, n = 125 vs. placebo, n = 65) to test the hypothesis that prophylactic clonidine reduces the incidence of perioperative myocardial ischemia and postoperative death in patients undergoing noncardiac surgery. Clonidine (0.2 mg orally as well as a patch) or placebo (tablet and patch) was administered the night before surgery, and clonidine (0.2 mg orally) or placebo (tablet) was administered on the morning of surgery. The patch or placebo remained on the patient for 4 days and was then removed.\n The incidence of perioperative myocardial ischemia was significantly reduced with clonidine (intraoperative and postoperative, 18 of 125, 14% vs. placebo, 20 of 65, 31%; P = 0.01). Prophylactic clonidine administration had minimal hemodynamic effects. Clonidine reduced the incidence of postoperative mortality for up to 2 yr (clonidine, 19 of 125 [15%] vs. placebo, 19 of 65 [29%]; relative risk = 0.43 [confidence interval, 0.21-0.89]; P = 0.035).\n Perioperative administration of clonidine for 4 days to patients at risk for coronary artery disease significantly reduces the incidence of perioperative myocardial ischemia and postoperative death.", "Patients with sleep apnea often present with cardiac diseases and breathing difficulties, with a high risk of postoperative respiratory depression. We conducted a randomized, double-blind, prospective study in 30 adult patients with obstructive sleep apnea, undergoing elective ear-nose-throat surgery. The patients were randomly assigned to receive placebo or clonidine (2 microg/kg oral) the night before and the next morning 2 h before surgery. Spo2, heart rate, mean arterial blood pressure, snoring, and oronasal airflow were monitored for 36 h. A standard anesthesia was used consisting of propofol and remifentanil. Anesthetic drug consumption, postoperative analgesics, and pain score were recorded. In the clonidine group, mean arterial blood pressures were significantly lower during induction, operation, and emergence from anesthesia. Both propofol dose required for induction (190 +/- 32.2 mg) and anesthesia (6.3 +/- 1.3 mg . kg(-1).h(-1)) during surgery were significantly reduced in the clonidine group compared with the placebo group (induction 218 +/- 32.4, anesthesia 7.70 +/- 1.5; P < 0.05). Piritramide consumption (7.4 +/- 5.1 versus 14.2 +/- 8.5 mg; P < 0.05) and analgesia scores were significantly reduced in the clonidine group. Apnea and desaturation index were not different between the groups, whereas the minimal postoperative oxygen saturation on the day of surgery was significantly lower in the placebo than in the clonidine group (76.7% +/- 8.0% versus 82.4% +/- 5.8%; P < 0.05). We conclude that oral clonidine premedication stabilizes hemodynamic variables during induction, maintenance, and emergence from anesthesia and reduces the amount of intraoperative anesthetics and postoperative opioids without deterioration of ventilation.", "To evaluate whether clonidine, enoximone, and enalaprilat reduce ischaemia-related myocardial cell damage in cardiac surgery.\n Prospective randomised controlled trial.\n Clinical investigation in a cardiac anaesthesia department of a university hospital.\n 88 consecutive patients undergoing coronary artery bypass surgery.\n After induction of anaesthesia patients continuously received the alpha 2 agonist clonidine (group 1, n = 22), the phosphodiesterase (PDE) III inhibitor enoximone (group 2, n = 22), the angiotensin converting enzyme (ACE) inhibitor enalaprilat (group 3, n = 22), or saline solution as placebo (control group, n = 22). The infusion was stopped immediately before the start of cardiopulmonary bypass.\n The ST segment was analysed and the activity of creatine kinase isoenzyme MB (CKMB), cardiac troponin T (TnT), and the BB isoenzyme of glycogen phosphorylase (GPBB) were measured before the start of infusion (baseline), after weaning from cardiopulmonary bypass (CPB), at the end of surgery, 5 h after CPB, and on the morning of the first and third postoperative days.\n Biometric data and time of cross-clamping were not significantly different in the four groups. Changes in the ST segment indicating ischaemia were least common in the enalaprilat group (P < 0.05). Postoperatively, CKMB activity was significantly higher in the clonidine and the control groups. Both new markers of myocardial cell damage increased more after CPB and postoperatively in the control patients (TnT peak: (mean (SD)) 3.99 (0.35) microgram/1; GPBB peak: 82 (15) ng/ml) and the clonidine-treated group (TnT peak: 3.80 (0.3) microgram/1; GPBB peak: 85 (14) ng/ml). Enalaprilat-treated patients showed the smallest overall changes in standard (CKMB) and new serological markers of myocardial ischaemia (TnT peak: 0.71 (0.1) microgram/1; GPBB peak: 44 (14) ng/ml).\n In patients treated with enalaprilat before CPB, both new, more sensitive markers of ischaemic myocardial tissue damage increased significantly less than in an untreated control group. Those treated with enoximone also had lower plasma concentration of TnT and GPBB than the control group, whereas clonidine did not reduce the concentration of these markers of myocardial ischaemia. Pharmacological interventions, such as the continuous infusion of the ACE inhibitor enalaprilat, before start of CPB may help to protect the heart against ischaemia/reperfusion injury.", "Dexmedetomidine was evaluated for sedation of 401 post-surgical patients in this double-blind, randomized, placebo-controlled, multicenter trial. Dexmedetomidine or saline was started on arrival in the intensive care unit (ICU) (1.0 mcg/kg for 10 minutes), then titrated at 0.2 to 0.7 mcg/kg/h to effect. Patients could be given propofol if necessary. Morphine was administered for pain. Sixty percent of the dexmedetomidine patients required no other sedative to maintain an RSS > or = 3; 21% required < 50 mg propofol. In contrast, 76% of the control group received propofol; 59% required > or = 50 mg. Dexmedetomidine patients required significantly less morphine for pain relief (P <.001). Continuously given throughout the ICU stay, dexmedetomidine had no effect on respiratory rate, oxygen saturation, duration of weaning, or times to extubation. Nurses judged the dexmedetomidine patients were easier to manage. Later, fewer dexmedetomidine patients remembered pain or discomfort. The majority of dexmedetomidine patients maintained blood pressures within normal range, without rebound. Hypertension, atelectasis, and rigors occurred more frequently in the control group, while hypotension and bradycardia occurred more frequently in the dexmedetomidine group. Preoperative cardiovascular conditions were not risk factors for dexmedetomidine patients.", "The utility of clonidine for hypertensive patients presenting for major vascular procedures remains debatable. Twenty-one hypertensive patients presenting for aortic surgery were given clonidine (n = 11) or placebo (n = 10) in a double-blind, randomized manner. Clonidine was administered 6 micrograms/kg per os 120 min before induction of anesthesia and 3 micrograms/kg intravenously (i.v.) over 60 min from aortic declamping to skin closure. Anesthesia was induced with alfentanil 20 micrograms/kg, midazolam, and atracurium and maintained with nitrous oxide 70%, an alfentanil infusion (0.25 microgram.kg-1. min-1), and isoflurane. Anesthetic requirements, circulatory variables, interventions, and isoproterenol dose-response curves (pre- and postoperatively) were determined. Plasma concentrations of clonidine, alfentanil, and vasoactive hormones were measured. When the clonidine group was compared with the placebo group, (a) isoflurane, alfentanil, and midazolam requirements were reduced by 38%, 42%, and 41%, respectively (P = 0.04, 0.03, 0.0002, respectively); (b) supplemental circulatory and anesthetic adjustments were reduced by 51% (P = 0.0006); (c) interventions with vasopressors were not significantly increased (placebo: two; clonidine: five); (d) systolic and mean arterial pressures and heart rate were reduced; (e) increases in norepinephrine, epinephrine, and plasma renin activity were suppressed, whereas vasopressin surge was attenuated; and (f) chronotropic response to isoproterenol was unaffected. Clonidine was effective in reducing anesthetic requirements and in improving circulatory stability in hypertensive patients presenting for major vascular procedures.", "Dexmedetomidine, a highly selective and potent alpha2-adrenergic agonist, has a potentially useful role as a sedative agent in patients requiring intensive care. As part of a larger European multicentre trial, a total of 119 postoperative cardiac and general surgical patients requiring ventilation and sedation in an intensive care unit were enrolled in four centres in the United Kingdom. One hundred and five patients were randomly allocated to receive either dexmedetomidine or placebo with rescue sedation and analgesia provided by midazolam and morphine, respectively. Compared with the control group, intubated patients receiving dexmedetomidine required 80% less midazolam [mean 4.9 (5.8) microg.kg-1.h-1 vs. 23.7 (27.5) microg.kg-1.h-1, p < 0.0001], and 50% less morphine [11.2 (13.4) microg.kg-1.h-1 vs. 21.5 (19.4) microg.kg-1.h-1,p = 0.0006]. Cardiovascular effects and adverse events could be predicted from the known properties of alpha-2 agonists. In conclusion, dexmedetomidine is a useful agent for the provision of postoperative analgesia and sedation.", "To compare dexmedetomidine-based to propofol-based sedation after coronary artery bypass graft (CABG) surgery in the intensive care unit (ICU).\n Randomized, open label.\n Twenty-five centers in the United States and Canada.\n Two hundred ninety-five adults undergoing CABG surgery.\n At sternal closure, patients in group A received 1.0 microg/kg of dexmedetomidine over 20 minutes and then 0.2 to 0.7 microg/kg/h to maintain a Ramsay sedation score > or =3 during assisted ventilation and > or =2 after extubation. Patients could be given propofol for additional sedation if necessary; group B patients received propofol-based care according to each investigator's standard practice.\n Mean sedation levels were within target ranges in both groups. Mean times to weaning and extubation were similar, although fewer dexmedetomidine patients remained on the ventilator beyond 8 hours. Morphine use was significantly reduced in the dexmedetomidine group. Only 28% of the dexmedetomidine patients required morphine for pain relief while ventilated versus 69% of propofol-based patients (p < 0.001). Propofol patients required 4 times the mean dose of morphine while in the ICU. Mean blood pressure increased initially in both groups, then decreased to 3 mmHg below baseline in dexmedetomidine patients; mean arterial pressure remained at 9 mmHg above baseline in propofol patients. No ventricular tachycardia occurred in the dexmedetomidine-sedated patients compared with 5% of the propofol patients (p = 0.007). Respiratory rates and blood gases were similar. Fewer dexmedetomidine patients received beta-blockers (p = 0.014), antiemetics (p = 0.015), nonsteroidal anti-inflammatory drugs (p < 0.001), epinephrine (p = 0.030), or high-dose diuretics (p < 0.001).\n Dexmedetomidine provided safe and effective sedation for post-CABG surgical patients and significantly reduced the use of analgesics, beta-blockers, antiemetics, epinephrine, and diuretics.", "nan", "We tested dexmedetomidine, an alpha(2) agonist that decreases heart rate, blood pressure, and plasma norepinephrine concentration, for its ability to attenuate stress responses during emergence from anesthesia after major vascular operations. Patients scheduled for vascular surgery received either dexmedetomidine (n = 22) or placebo (n = 19) IV beginning 20 min before the induction of anesthesia and continuing until 48 h after the end of surgery. All patients received standardized anesthesia. Heart rate and arterial blood pressure were kept within predetermined limits by varying anesthetic level and using vasoactive medications. Heart rate, arterial blood pressure, and inhaled anesthetic concentration were monitored continuously; additional measurements included plasma and urine catecholamines. During emergence from anesthesia, heart rate was slower with dexmedetomidine (73 +/- 11 bpm) than placebo (83 +/- 20 bpm) (P = 0.006), and the percentage of time the heart rate was within the predetermined hemodynamic limits was more frequent with dexmedetomidine (P < 0.05). Plasma norepinephrine levels increased only in the placebo group and were significantly lower for the dexmedetomidine group during the immediate postoperative period (P = 0.0002). We conclude that dexmedetomidine attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia.\n The alpha(2) agonist, dexmedetomidine, attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia in vascular surgery patients.", "To compare dexmedetomidine vs. placebo with respect to the amount of additional propofol and morphine used for bispectral index-guided sedation and analgesia in mechanically ventilated, intensive care patients after surgery.\n Prospective, randomized, double blind, placebo-controlled, phase II clinical trial.\n General surgical and cardiac surgical intensive care units.\n Thirty patients scheduled for major surgery requiring mechanical ventilation for a minimum of 6 hrs were included in the study.\n Patients were assigned randomly to receive either dexmedetomidine (loading infusion, 6.0 microg x kg(-1) x hr(-1) for 10 mins; maintenance infusion, 0.1-0.7 microg x kg(-1) x hr(-1)) or placebo after intensive care unit admission.\n Sedation was guided by using the electroencephalographic parameter bispectral index, a new noninvasive method to estimate the level of sedation. We aimed at maintaining bispectral index ranges between 60 and 70 during mechanical ventilation before starting weaning, 65 and 95 during weaning, and 85 to 95 postextubation. Additional sedative and analgesic medication was given (propofol and morphine) as clinically indicated and within the previously mentioned bispectral index ranges. Patients receiving dexmedetomidine required significantly less propofol during mechanical ventilation (0.87 +/- 0.21 vs. 1.52 +/- 0.30 mg x kg(-1) x hr(-1); p <.01) and weaning (0.17 +/- 0.06 vs. 0.62 +/- 0.21 mg x kg(-1) x hr(-1); p <.001) to maintain the target bispectral index range. During study drug administration, morphine requirements for dexmedetomidine-treated patients were reduced by 58% (p =.05). Hemodynamic stability during weaning and after extubation was better maintained in patients receiving dexmedetomidine.\n Dexmedetomidine reduced propofol requirements and improved hemodynamic stability during bispectral index-guided intensive care unit sedation.", "The effect of oral premedication with 300 micrograms of clonidine on systemic arterial pressure, heart rate, and plasma norepinephrine levels was assessed in a double-blinded, placebo-controlled study conducted in 29 patients subjected to carotid artery surgery (CAS). Anesthesia was induced with thiopental, 6 mg/kg, and alfentanil, 0.05 mg/kg, and maintained with alfentanil and 0.6% isoflurane in 50% N20/O2. The study was divided into five periods as follows: (1) anesthesia to start of surgery; (2) surgery to carotid artery clamping; (3) carotid artery clamping to unclamping; (4) carotid artery unclamping to the end of surgery; and (5) the first 4 postoperative hours in the recovery room. In the clonidine group (n = 14), plasma norepinephrine concentrations were significantly lower before induction of anesthesia and during the operative period. Heart rate and systemic arterial pressure were lower (P less than 0.01) in the clonidine group at 3 different time intervals (control, carotid clamping, carotid unclamping). However, during each of the previously defined periods, the variability of heart rate and systemic arterial pressure, assessed by the coefficient of variation, was not different between the two groups. The lability of these hemodynamic parameters, expressed as the percentage of values, which increased or decreased more than 20% of control values during the corresponding period, was also comparable between the two groups. The number of patients who experienced at least one episode of hypertension (systolic arterial pressure greater than 180 mm Hg), hypotension (systolic arterial pressure less than 100 mm Hg), or bradycardia less than 45 beats/min was not different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "The alpha2 agonist dexmedetomidine is a new sedative and analgesic agent which is licensed in the USA for post-operative intensive care sedation. We compared dexmedetomidine with propofol in patients requiring sedation in intensive care. Twenty adult patients expected to require a minimum of 8 h artificial ventilation after surgery were randomized to receive sedation with either dexmedetomidine or propofol infusions. Additional analgesia, if required, was provided by an alfentanil infusion. Depth of sedation was monitored using both the Ramsay sedation score (RSS) and the bispectral index (BIS). Cardiovascular, respiratory, biochemical and haematological data were obtained. Patients' perceptions of their intensive care stay were assessed using the Hewitt questionnaire. Sedation was equivalent in the two groups [median (interquartile range): RSS, propofol group 5 (4-5), dexmedetomidine group 5 (4-6) (P=0.68); BIS, propofol group 53 (41-64), dexmedetomidine group 46 (36-58); P=0.32], but the propofol group received three times more alfentanil compared with patients sedated with dexmedetomidine [2.5 (2.2-2.9) mg h(-1) versus 0.8 (0.65-1.2) mg h(-1) (P=0.004)]. No differences were found in arterial pressures between the groups, but heart rate was significantly lower in the dexmedetomidine group [mean (SD) 75 (6) vs 90 (4) beats min(-1)]. Extubation times were similar and rapid with the use of both sedative agents [median (range) 28 (20-50) and 29 (15-50) min (P=0.63) respectively for the propofol and dexmedetomidine groups]. No adverse events related to the sedative infusions occurred in either group. Despite ventilation and intubation, patients sedated with dexmedetomidine could be easily roused to cooperate with procedures (e.g. physiotherapy, radiology) without showing irritation. From the clinician's and patient's perspectives, dexmedetomidine is a safe and acceptable sedative agent for those requiring intensive care. The rate pressure product is reduced in patients receiving dexmedetomidine, which may protect against myocardial ischaemia. Dexmedetomidine reduces the requirement for opioid analgesia.", "The purpose of this study was to determine if clonidine reduces myocardial ischemia or alters anesthetic requirement and perioperative hemodynamic parameters during coronary artery bypass grafting (CABG) surgery. Forty-three patients were randomized in a prospective, double-blind fashion to receive either clonidine (5 micrograms/kg) or placebo. Anesthetic induction and maintenance was accomplished with intravenous sufentanil-midazolam (S-M) in a 1:20 ratio; up to 1.0% enflurane was added during surgery when repeated boluses of S-M failed to maintain the blood pressure within 20% of preinduction values. Continuous ST segment analysis of leads II and V5 was performed throughout surgery with maximal ST segment deflection from baseline recorded every 5 minutes. Catecholamine levels were measured intermittently throughout the perioperative period and myocardial lactate use or excretion was determined just prior to cardiopulmonary bypass (CPB) and at 1, 5, 10, 30, and 60 minutes after release of the aortic cross-clamp. Patients who received clonidine required significantly less sufentanil for their surgical procedure (11.82 +/- 0.66 micrograms/kg v 14.55 +/- 0.90 micrograms/kg, P < 0.05) and also needed less enflurane for blood pressure control, particularly during CPB (P < 0.05). Baseline hemodynamic parameters were similar for both groups prior to induction. In the period between anesthetic induction and the initiation of CPB, patients treated with clonidine had a significantly slower heart rate (HR) (P < 0.01), a lower cardiac output (CO) (P < 0.05), and transiently higher systemic vascular resistance (SVR) (P < 0.05) than placebo-treated patients. Immediately after CPB, patients receiving clonidine continued to have a significantly lower CO (P < 0.01) and a higher SVR (P < 0.01) than placebo-treated patients. Clonidine treatment significantly increased the percentage of patients who required pacing after CPB (P < 0.05). In the intensive care unit, clonidine-treated patients displayed a persistently increased requirement for pacing (P < 0.01), decreased systolic blood pressures, and reduced sodium nitroprusside requirements relative to patients treated with placebo. Epinephrine and norepinephrine levels were lower in clonidine-treated patients throughout the perioperative procedure with significant differences noted immediately following sternotomy and release of the aortic cross-clamp (P < 0.05). Critical ST segment depression was significantly less in clonidine-treated patients for the period from sternotomy until application of the aortic cross-clamp (P < 0.01). Following CPB, absolute deviation of ST segments from isoelectric baseline was significantly less in the clonidine-treated group (P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)", "In this prospective study, we evaluated whether high thoracic epidural anesthesia (TEA) or i.v. clonidine, in addition to general anesthesia, affects the cardiopulmonary bypass- and surgery-associated stress response and incidence of myocardial ischemia by their sympatholytic properties. Seventy patients scheduled for elective coronary artery bypass graft (CABG) received general anesthesia with sufentanil and propofol. TEA was randomly induced before general anesthesia and continued during the study period in 25 (anesthetized dermatomes C6-T10). Another 24 patients received i.v. clonidine as a bolus of 4 microg/kg before the induction of general anesthesia. Clonidine was then infused at a rate of 1 microg x kg(-1) x h(-1) during surgery and at 0.2-0.5 microg x kg(-1) x h(-1) postoperatively. The remaining 21 patients underwent general anesthesia as performed routinely (control). Hemodynamics, plasma epinephrine and norepinephrine, cortisol, the myocardial-specific contractile protein troponin T, and other cardiac enzymes were measured pre- and postoperatively. During the preoperative night and a follow-up of 48 h after surgery, five-lead electrocardiogram monitoring was used for ischemia detection. Both TEA and clonidine reduced the postoperative heart rate compared with the control group without jeopardizing cardiac output or perfusion pressure. Plasma epinephrine increased perioperatively in all groups but was significantly lower in the TEA group. Neither TEA nor clonidine affected the increase in plasma cortisol. The release of troponin T was attenuated by TEA. New ST elevations > or = 0.2 mV or new ST depression > or = 0.1 mV occurred in > 70% of the control patients but only in 40% of the clonidine group and in 50% of the TEA group. We conclude that TEA (but not i.v. clonidine) combined with general anesthesia for CABG demonstrates a beneficial effect on the perioperative stress response and postoperative myocardial ischemia. Implications: Thoracic epidural anesthesia combined with general anesthesia attenuates the myocardial sympathetic response to cardiopulmonary bypass and cardiac surgery. This is associated with decreased myocardial ischemia as determined by less release of troponin T. These findings may have an impact on the anesthetic management for coronary artery bypass grafting.", "Mivazerol hydrochloride is a new alpha 2-adrenoceptor agonist. In vitro and animal studies have demonstrated both sympatholytic and antiischemic properties. To evaluate the safety and efficacy of mivazerol in patients during perioperative stress, this multicenter phase II clinical trial studied hemodynamic stability and myocardial ischemia in patients with coronary artery disease undergoing noncardiac surgery.\n Three hundred patients, from twenty-three European medical institutions, participated in this placebo-controlled, double-blind, randomized, parallel-group trial. Ninety-eight were given high-dose mivazerol (1.5 micrograms.kg-1.h-1); 99, low-dose mivazerol (0.75 microgram.kg-1.h-1); and 103, placebo, continuously intraoperatively and for 72 h postoperatively. Blood pressure and heart rate were monitored for 96 h. Myocardial ischemia was assessed by Holter electrocardiography for at least 8 h before induction of anesthesia until 96 h after surgery. Twelve-lead electrocardiograms and creatine kinase myocardial band isoenzyme levels were obtained before and serially after surgery. Adverse cardiac events were assessed for the intraoperative, early postoperative (0-24 h), and late postoperative (24-72 h) periods.\n The incidence of tachycardia was significantly lower with high-dose mivazerol (vs. placebo) during the intraoperative (30% vs. 51%; P = 0.002), early postoperative (29% vs. 50%; P = 0.002), and late postoperative periods (46% vs. 70%; P = 0.001). Also, the percentage of patients treated for tachycardia was significantly lower with the high dose (vs. placebo) during the early (10% vs. 20%; P = 0.043) and late (6% vs. 15%; P = 0.024) postoperative periods. The incidence of hypertension was significantly lower with both high and low doses (vs. placebo) during the intraoperative period (46% and 43%, respectively, vs. 63%; P = 0.010); treatment was similar at both high and low doses (33% and 34%, respectively, vs. 46%; P = 0.066). The incidence of bradycardia was significantly higher at both dose levels than with placebo during and after drug administration (intraoperatively-3%, 7%, and 9%; early postoperative-0%, 5%, and 6%; late postoperative-0%, 4%, and 6%; after drug-0%, 6%, and 6%; placebo, low-dose, high-dose, respectively), but the need for treatment did not differ for the groups. The incidence of, and treatment for, hypotension were similar for the three groups. Intraoperative myocardial ischemia was significantly lower with high-dose mivazerol than with placebo (20% vs. 34%, respectively, P = 0.026). When intraoperative data were subdivided into emergence vs. nonemergence periods (post boc analysis), the incidence of myocardial ischemia was significantly lower with high-dose mivazerol than with placebo during emergence (11% vs. 30%; P = 0.001). Regarding blood pressure, heart rate, and ischemia, no rebound response occurred in the 12 h after discontinuation of mivazerol. The high-dose, low-dose, and placebo groups did not differ in the incidence of adverse cardiac outcomes (3%, 2%, and 8%, respectively) or the diagnosis of myocardial infarction (2%, 1%, and 6%, respectively).\n Continuous, 72-h perioperative administration of mivazerol to high-risk patients appears to be relatively safe, producing no significant hypotension or adverse events but some evidence of bradycardia not associated with adverse clinical events. Mivazerol decreased the incidence of, and treatment for, tachycardia, hypertension, and myocardial ischemia, particularly during high stress periods. Therefore, these salutary effects of mivazerol indicate further study in large-scale trials that assess mivazerol's effects on adverse cardiac outcomes, including death and myocardial infarction.", "The purpose of this study was to assess the efficacy of clonidine in achieving perioperative hemodynamic stability in patients undergoing coronary artery bypass grafting performed under high-dose alfentanil anesthesia. Twenty-four patients with left ventricular ejection fraction greater than 0.5 were prospectively studied in a double-blind manner; those requiring emergency procedures were excluded. They were randomized to receive either oral clonidine or placebo together with their premedication. Induction of anesthesia was achieved with 10 mg of alfentanil infused over 5 minutes followed by a continuous infusion of 60 mg/h during 1 hour, or until sternotomy, and then 30 mg/h until the end of surgery. Hemodynamic responses to noxious stimuli were treated with additional alfentanil boluses and isoflurane when these were unsuccessful. Intraoperative hemodynamic profile analyses showed a continuous increase in systemic vascular resistance and mean arterial pressure in the clonidine group from the time of skin incision until the onset of bypass, whereas the cardiac output profiles remained similar in the two groups. The number of additional alfentanil boluses was similar. Isoflurane requirements (1/11 v 4/13) were not significantly different, but only a few patients required this therapy. The postbypass hemodynamic profiles were similar. Severe hemodynamic impairment occurred in the clonidine group during warming in the postoperative period: this group showed a drop in systemic vascular resistance index (1276 +/- 347 v 1757 +/- 415 dyn.sec.cm-5.m2) that could not be compensated for by an increase in cardiac output despite normal filling pressures, causing hypotension (66 +/- 10 v 79 +/- 16 mmHg). This hemodynamic status led to greater requirements for vasoactive agents and inotropics in this group.(ABSTRACT TRUNCATED AT 250 WORDS)", "Clonidine may have beneficial effects in patients undergoing major surgery. We enrolled 156 patients having elective CABG surgery in a double-blind, randomized trial. Patients were randomized to receive either two doses of placebo (Group PP) or clonidine 5 micrograms/kg (Group CC). Perioperative measurements included haemodynamics, anaesthetic and analgesic drug usage, creatinine clearance, cortisol excretion, recovery times and quality of life (SF-36) after surgery. Overall, there was no significant difference with time to tracheal extubation (median [10-90 centile]): CC 7.1 (3.4-18) h vs PP 8.0 (4.3-17) h, P = 0.70; but there was a higher proportion of patients extubated within four hours: CC 20% vs. PP 8%, P = 0.038. Clonidine resulted in a number of significant (P < 0.05) haemodynamic changes, particularly pre-CPB: less tachycardia and hypertension, more bradycardia and hypotension. Clonidine was associated with a significant (P < 0.05) reduction in anaesthetic drug usage, higher creatinine clearance, lower cortisol excretion and improvement in some aspects of quality of life. This study lends support to consideration of clonidine therapy in patients undergoing CABG surgery.", "The usual hemodynamic response to laryngoscopy and bronchoscopy is an increase in heart rate and arterial blood pressure. Previous work has reported that 10%-18% of the patients develop ischemic ST segment changes during the procedure. Therefore, we performed a prospective, randomized, double-blinded study in 36 patients scheduled for elective microlaryngeal and bronchoscopic surgical procedures to evaluate the effects of 300-microg oral clonidine premedication (n = 18) or placebo (n = 18) on the hemodynamic alterations and the incidence of perioperative myocardial ischemic episodes. Myocardial ischemia was assessed by using continuous electrocardiographic monitoring, beginning 30 min before, and lasting until 24 h after the operation. During the procedure, patients receiving placebo exhibited a significant increase (mean +/- SD) in arterial blood pressure (the systolic increasing from 137+/-11 to 166+/-17 mm Hg, the diastolic increasing from 80+/-11 to 97+/-14 mm Hg) and heart rate (increasing from 79+/-15 to 97+/-12 bpm) compared with the baseline and with the clonidine group. A dose of 300-microg clonidine blunted the hemodynamic response to endoscopy. Ventricular arrhythmias were more frequent in patients who were not premedicated with clonidine. Two patients in the control group, but none in the clonidine group, had evidence of myocardial ischemia. These data should encourage routine premedication with clonidine in patients undergoing microlaryngoscopic and bronchoscopic procedures.", "The purpose of this study was to test the hypothesis that after thoracic surgery, the supplementation of a low-dose thoracic epidural (ED) bupivacaine (0.125%) infusion by intravenous (IV) dexmedetomidine decreases analgesic requirement without causing respiratory depression. The primary endpoint was the need for additional ED bupivacaine administered through patient-controlled epidural analgesia (PCEA). Secondary endpoints included the requirement for supplemental opioids and the impact of dexmedetomidine on CO2 retention.\n A prospective, randomized, double-blinded study.\n A major US tertiary care university hospital.\n Twenty-eight patients scheduled to undergo elective thoracotomy for wedge resection, lobectomy, or pneumonectomy.\n On intensive care unit arrival, the thoracic ED catheter was loaded with 0.125% bupivacaine to a T4 sensory level and a continuous infusion of 0.125% bupivacaine without opioid was commenced at 4 mL/h. Patients were then randomized into 1 of 2 groups. The dexmedetomidine group received an IV loading dose of dexmedetomidine of 0.5 microg/kg over 20 minutes, followed by continuous IV infusion at 0.4 microg/kg/h. The placebo group received IV saline at the same calculated loading and infusion rates by volume. If necessary, supplemental analgesia (increased ED rate, ED fentanyl, ketorolac [IV]) was provided to ensure a visual analog scale (VAS) score of < or =3.\n The analgesic effect was monitored by the VAS, and the requirement for PCEA dosing and additional analgesics was recorded. Heart rate, blood pressure, and blood gases were also monitored.\n There was no significant difference in PCEA use and VAS score between the 2 groups, but requirement for supplemental ED fentanyl analgesia was significantly greater in the placebo group (66.1 +/- 95.6 v 5.3 +/- 17.1 microg, p = 0.039). Mean PaCO2 was also significantly greater in the placebo group (40.3 +/- 4.1 v 43.9 +/- 4.3 mmHg, p = 0.04). Patients in the dexmedetomidine group exhibited significantly decreased heart rate (1 patient required and responded to atropine) and blood pressure (4 patients required and readily responded to IV fluid) compared with the placebo group.\n The authors conclude that in postthoracotomy patients, IV dexmedetomidine is a potentially effective analgesic adjunct to thoracic ED bupivacaine infusion and may decrease the requirement for opioids and potential for respiratory depression." ]

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[ "Effect of high-flux dialysis on the anaemia of haemodialysis patients.", "Biocompatible membranes preserve residual renal function in patients undergoing regular hemodialysis.", "Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters. The Italian Cooperative Dialysis Study Group.", "Are high flux dialysis and erythropoietin treatment in a collision course?", "Effect of dialysis dose and membrane flux in maintenance hemodialysis.", "Complement activation in dialysis: effects on cytokines, lymphocyte activation and beta 2 microglobulin.", "Effect of membrane permeability on inflammation and arterial stiffness: a randomized trial.", "The effect of high-flux hemodialysis on dialysis-associated amyloidosis.", "Preservation of residual renal function in dialysis patients: effects of dialysis-technique-related factors.", "High-flux dialysis membranes improve lipid profile in chronic hemodialysis patients.", "High flux dialysis membranes improve plasma lipoprotein profiles in patients with end-stage renal disease.", "Influence of hemodialysis membrane permeability on serum levels of advanced glycation end products (AGEs) and homocysteine metabolites.", "High-flux hemodialysis postpones clinical manifestation of dialysis-related amyloidosis.", "Reduction of plasma apolipoprotein-B by effective removal of circulating glycation derivatives in uremia.", "Effect of high-flux hemodialysis on quality of life and neuropsychological function in chronic hemodialysis patients.", "Tolerance of hemodialysis: a randomized prospective trial of high-flux versus conventional high-efficiency hemodialysis.", "Effects of low- and high-flux dialyzers on oxidative stress and insulin resistance.", "Beta 2-microglobulin generation and removal in long slow and short fast hemodialysis.", "Randomized trial of high-flux vs low-flux haemodialysis: effects on homocysteine and lipids.", "Indices of adequate dialysis in patients hemodialyzed with AN 69 membrane.", "Does treatment modality have an impact on anemia in patients with chronic renal failure? Effect of low- and high-flux biocompatible dialysis.", "Effect of membrane permeability on survival of hemodialysis patients.", "Effect of dialyser membrane pore size on plasma homocysteine levels in haemodialysis patients.", "Do high-flux dialysis membranes affect renal dyslipidemia?" ]

[ "Anaemia is one of the major clinical characteristics of patients with chronic renal failure, and has a considerable effect on morbidity and mortality. Adequate dialysis is of paramount importance in correcting anaemia by removing small and medium-sized molecules, which may inhibit erythropoiesis. However, high-molecular-weight inhibitors cleared only by means of highly porous membranes have also been found in uraemic serum and it has been claimed from uncontrolled studies that high-flux dialysis could improve anaemia in haemodialysis patients.\n We therefore planned this multicentre randomized controlled trial with the aim of testing whether the use of a large-pore biocompatible membrane for a fixed 12-week follow-up improves anaemia in haemodialysis patients in comparison with the use of a conventional cellulose membrane. Eighty-four (5.3%) of a total of 1576 adult haemodialysed patients attending 13 Dialysis Units fulfilled the entry criteria and were randomly assigned to the experimental treatment (42 patients) or conventional treatment (42 patients).\n Haemoglobin levels increased non-significantly from 9.5+/-0.8 to 9.8+/-1.3 g/dl (dP=0. 069) in the population as a whole, with no significant difference between the two groups (P:=0.485). Erythropoietin therapy was given to 32/39 patients (82%) in the conventional group, and 26/35 (74%) in the experimental group (P:=0.783) with subcutaneous administration to 26/32 patients in conventional and to 23/26 patients in experimental group, P:=0.495. Dialysis dose (Kt/V) remained constant in both groups (from 1.30+/-0.17 to 1.33+/-0.20 in the conventional group and from 1.28+/-0.26 to 1.26+/-0.21 in the experimental group, P:=0.242). Median pre- and post-dialysis beta(2)-microglobulin levels remained constant in the conventional group (31.9 and 34.1 mg/dl at baseline) and decreased in the experimental group (pre-dialysis values from 31.1 to 24.7 mg/dl, P:=0.004 and post-dialysis values from 24.8 to 20.8 mg/dl, P:=0.002). Median erythropoietin doses were not different at baseline (70 IU/kg/week in conventional treatment and 90 IU/kg/week in experimental treatment, P:=0.628) and remained constant during follow-up (from 70 to 69 IU/kg/week in the conventional group and from 90 to 91 IU/kg/week in the experimental group, P:=0.410). Median erythropoietin plasma levels were in the normal range and remained constant (from 12.1 to 12.9 mU/ml in the conventional group and from 13.2 to 14.0 mU/ml in the experimental group, P:=0.550).\n This study showed no difference in haemoglobin level increase between patients treated for 3 months with a high-flux biocompatible membrane in comparison with those treated with a standard membrane. When patients are highly selected, adequately dialysed, and have no iron or vitamin depletion, the effect of a high-flux membrane is much less than might be expected from the results of uncontrolled studies.", "Initiation of hemodialysis causes a further decrease of residual renal function (RRF). To assess the impact of the biocompatibility of the dialysis membrane, we performed a prospective randomized investigation in 20 normotensive patients with tubulointerstitial nephritis. The patients were randomly allocated to treatment with either a high-flux polysulfone or cellulose membrane over a period of 12 months. RRF, defined by creatinine clearance and daily urine volume, was found to decrease in both groups of patients after the initiation of hemodialysis. Of the two membranes used, however, the cellulose membrane caused an accelerated decrease of RRF (P < 0.05). The better maintenance of RRF in patients treated with polysulfone membranes was associated with higher Kt/V values and increased hematocrit values (P < 0.05). The pathophysiologic mechanism underlying the more rapid decline of RRF could not be explained by intradialytic hypotension, but may be related to the nephrotoxic effects of inflammatory mediators due to bioincompatibility. Therefore, the use of polysulfone membranes might be preferable in patients with relevant RRF.", "There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage (in terms of treatment tolerance, nutritional parameters and pre-treatment beta-microglobulin levels) over a traditional membrane (Cuprophan). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan hemodialysis (Cu-HD), low-flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 +/- 10.46 mg/liter (23%) and in hemodiafiltration of 6.35 +/- 12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes (P = 0.032). The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications.", "Twenty patients treated with human recombinant erythropoietin (EPO) for 9 months were studied. The patients were randomly allocated to high flux (HF) or conventional dialysis (CD). Patients on HF used the F-60 or F-80 dialyzer, with a polysulfone membrane; QB: 470 ml/min; QD: 800 ml/min; t: 127 min; Kt/V: 1.01. Conventional dialysis patients used regenerated cellulosic membranes; QB: 297 ml/min; QD: 500 ml/min; t: 193 min; Kt/V: 1.05. Mean dose of EPO was 103 U/kg for HF patients and 112.4 U/kg for patients on CD. At 9 months, no significant differences were observed in HCT (HF 33.6% vs. CD 33.2%), BUN, serum creatinine, potassium, or phosphorus. Hemoconcentration during dialysis was 12% for HF and 17% for CD. Urea clearance decreased 7% for HF and 9% for CD, while clearance of creatinine, potassium, and phosphorus decreased between 14 and 18% with both treatments. Heparin requirements increased 10% in HF and 16% in CD. Hypertension was similar in both groups. One HF patient withdrew from the study because of hypertension and one HF patient had seizures related to hypertension. Vascular access clotting or hospitalizations were no different. High flux dialysis patients on EPO over a 9 month period did not have any catastrophic complications when HCT was maintained between 30 and 35%.", "The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain.\n We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer.\n In the standard-dose group, the mean (+/-SD) urea-reduction ratio was 66.3+/-2.5 percent, the single-pool Kt/V was 1.32+/-0.09, and the equilibrated Kt/V was 1.16+/-0.08; in the high-dose group, the values were 75.2+/-2.5 percent, 1.71+/-0.11, and 1.53+/-0.09, respectively. Flux, estimated on the basis of beta2-microglobulin clearance, was 3+/-7 ml per minute in the low-flux group and 34+/-11 ml per minute in the high-flux group. The primary outcome, death from any cause, was not significantly influenced by the dose or flux assignment: the relative risk of death in the high-dose group as compared with the standard-dose group was 0.96 (95 percent confidence interval, 0.84 to 1.10; P=0.53), and the relative risk of death in the high-flux group as compared with the low-flux group was 0.92 (95 percent confidence interval, 0.81 to 1.05; P=0.23). The main secondary outcomes (first hospitalization for cardiac causes or death from any cause, first hospitalization for infection or death from any cause, first 15 percent decrease in the serum albumin level or death from any cause, and all hospitalizations not related to vascular access) also did not differ significantly between either the dose groups or the flux groups. Possible benefits of the dose or flux interventions were suggested in two of seven prespecified subgroups of patients.\n Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane.\n Copyright 2002 Massachusetts Medical Society", "Anaphylatoxins generated by complement activation by filter membranes are present in plasma during hemodialysis (HD). In the presence of endotoxins which may contaminate the dialysate, they can trigger monocytes to produce interleukin-1 (IL-1) and tumor necrosis factor (TNF), with detrimental effects for the patients. We have investigated whether or not the use of complement activating (cuprophan) and non- (or less-) activating membranes (polysulfone, polymethylmethacrylate or polyacrylonitrile) per se influences cytokine levels in HD patients. Our results indicate that if a sterile bicarbonate solution is used as dialysate, there are no significant increases in IL-1, TNF, interleukin-2 (IL-2) and soluble IL-2 receptors (sIL-2r) throughout HD, even with cuprophan membranes. Moreover even a prolonged use of this membrane (three months) did not change pre-dialysis levels of cytokines and receptors. Use of complement activating membranes also does not influence beta 2 microglobulin levels.", "Both larger molecule removal and dialyzer biocompatibility have been implicated in the high-flux hemodialysis (HD)-associated favorable outcome. In an attempt to delineate the effect of membrane permeability, we performed a randomized, crossover study to compare the inflammatory biomarkers, lipid profile, and aortic pulse wave velocity (PWV) of two dialyzers that are composed of identical membranes but with different flux characteristics.\n Stable patients who had anuria and were on low-flux polysulfone membrane were randomly allocated either to HD with high-flux polyamide membrane (group A; 22 patients) or to HD with low-flux polyamide membrane (group B; 24 patients) for 24 weeks, then they were started on 24 weeks of the alternative HD treatment. Apart from the dialyzer, the dialysis prescription remained unchanged.\n Nineteen patients from group A and 23 patients from group B completed the study. Predialysis beta(2)-microglobulin levels decreased significantly when using the high-flux polyamide membrane. No difference between membranes was observed for serum albumin, high-sensitivity C-reactive protein, fibrinogen, IL-6, triglycerides, HDL cholesterol, LDL cholesterol, and lipoprotein(a) during the study. A significant increase in aortic PWV, a marker of aortic stiffness, was noted after patients switched from high-flux to low-flux polyamide membranes. Similarly, the rate of change in aortic PWV was significantly decreased with the use of the high-flux polyamide membrane.\n Our findings suggest that dialysis with polyamide membranes with different flux characteristics did not modify the inflammatory indices and lipid profile in stable HD patients; however, a seemingly beneficial effect on aortic stiffness was noted for patients who were maintained on high-flux polyamide membrane.", "Amyloidosis is an important cause of mortality and morbidity in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). In this study, depending on the idea that the clearance of middle and high molecular weight toxins could be improved, we aimed to investigate the effect of high-flux dialyzer on clearance of beta-2 microglobulin (beta2-MG) and calcium (Ca) phosphorus (P) metabolism in patients under HD treatment. Forty-eight patients with ESRD under chronic HD treatment were included in the study. All patients were randomized into two groups, and HD was performed with low-flux or high-flux dialyzer for 6 months. In the high-flux group, the reduction of beta2-MG and P levels during dialysis was significantly higher when compared with the low-flux group (p<0.001). During the follow-up period, while beta2-MG levels decreased significantly in the high-flux group (p<0.05), there was an increase in the low-flux group (p<0.05). As a result, our findings suggest that use of high-flux dialyzer can be an efficient alternative in terms of controlling the clearance of beta2-MG and impaired Ca and P metabolism. These beneficial effects of high-flux dialyzers are probably mediated by the improved clearance of middle and high molecular weight toxins.", "Residual renal function (RRF) is of paramount importance to dialysis adequacy, morbidity, and mortality, particularly for long-term continuous ambulatory peritoneal dialysis (CAPD) patients. Residual renal function seems to be better preserved in patients on CAPD than in hemodialysis (HD) patients. We analyzed RRF in 45 patients with end-stage renal disease (ESRD), commencing either CAPD or HD, to prospectively define the time course of the decline in RRF, and to evaluate dialysis-technique-related factors such as cardiovascular stability and bioincompatibility.\n Single-center prospective investigation in parallel design with matched pairs.\n Fifteen patients starting CAPD and 15 matched pairs of patients commencing HD were matched according to cause of renal failure and RRF. Hemodialysis patients were assigned to two dialyzer membranes differing markedly in their potential to activate complement and cells (bioincompatibility). Fifteen patients were treated exclusively with the cuprophane membrane (bioincompatible) and the other 15 patients received HD with the high-flux polysulfone membrane (biocompatible).\n Residual renal function was determined at initiation of dialytic therapy and after 6, 12, and 24 months. Dry weight (by chest x ray and diameter of the vena cava) was closely recorded throughout the study, and the number of hypotensive episodes counted.\n Residual renal function declined in both CAPD and HD patients, although this decline was faster in HD patients (2.8 mL/minute after 6 months and 3.7 mL/min after 12 months) than in CAPD patients (0.6 mL/min and 1.4 mL/min after 6 and 12 months respectively). It declined faster in patients with bioincompatible than with biocompatible HD membranes (3.6 mL/min vs 1.9 mL/min after 6 months). Eleven percent of the HD sessions were complicated by clinically relevant blood pressure reductions, but there were no differences between the two dialyzer membrane groups. None of the CAPD patients had documented hypotensive episodes. None of the study patients suffered severe illness or received nephrotoxic antibiotics or radiocontrast media.\n The better preservation of RRF in stable CAPD patients corresponded with greater cardiovascular stability compared to HD patients, independently of the membrane used. Furthermore, there was a significantly higher preservation of RRF in HD patients on polysulfone versus cuprophane membranes, indicating an additional effect of biocompatibility, such as less generation of nephrotoxic substances by the membrane. Thus, starting ESRD patients on HD prior to elective CAPD should be avoided for better preservation of RRF.", "In a controlled prospective trial, the effect of a switch from cellulose-based, low-flux dialysis membranes to polysulphone, high-flux membranes on lipid parameters was evaluated. Baseline values of lipid parameters were identical in the study group and the control group in which the dialysis membrane remained unchanged. After 6 wk, total triglyceride, very low-density lipoprotein (VLDL) triglyceride, and VLDL cholesterol decreased, respectively, 28 +/- 17 (P < 0.01), 38 +/- 17 (P < 0.01), and 24 +/- 21% (P < 0.05), and the proportion of total cholesterol that was high-density lipoprotein cholesterol increased from 15 +/- 5 to 18 +/- 5% (P < 0.05) in the high-flux polysulphone group, whereas these variables remained unchanged in the control group. Low-density lipoprotein and total cholesterol as well as Kt/V, protein catabolic rate, parathyroid hormone, albumin, and body weight did not change. No change in lipoprotein lipase activity was found. In a second study, the effects of a single hemodialysis session with high-flux polysulphone and low-flux, cellulose-based membranes on lipid parameters and lipolytic activity were compared in a cross-over fashion. Treatment with both membranes resulted in a significant decrease in plasma triglyceride, VLDL triglyceride, and VLDL cholesterol. Lipoprotein lipase activity increased during hemodialysis. Changes in lipid parameters and lipolytic activity were identical during the two treatments.", "A major cause of the morbidity and mortality of patients with end-stage renal disease (ESRD) is related to disorders of large blood vessels, especially coronary heart disease. Atherosclerosis, the most common form of this disease, is known to result from abnormalities in plasma lipoproteins, as well as from factors that damage the vessel wall. Two well-known risk factors for coronary heart disease are elevated plasma concentrations of LDL and reduced concentrations of HDL. This latter disorder is often accompanied by elevated triglycerides. Low HDL and elevated triglycerides are commonly associated with ESRD. Dialysis with high flux membranes differs from conventional dialysis in a number of ways. These include better biocompatibility and increased flux of larger molecules. Although several previous studies had suggested that dialysis with high flux membranes improves plasma lipoprotein profiles, a definitive cross-over designed study to assess the roles of high flux versus biocompatibility in altering lipoprotein profiles had not been done. Preliminary data from such a study are presented. These data confirm the beneficial effects of high flux membranes to reduce plasma triglycerides and suggest that this effect is primarily due to the high flux, and not the biocompatible, feature of the membranes.", "[corrected] Advanced glycation end products (AGEs), total homocysteine (tHcy) and the homocysteine metabolites cystathionine (Cysta) and dimethylglycine (DMG) are increased in serum of patients with end-stage renal disease. The aim of this prospective randomized study was to compare the efficacy of polysulfone high-flux vs. polysulfone low-flux hemodialysis (HD) treatment regarding removal of AGEs, tHcy, Cysta and DMG.\n Twenty-nine patients on chronic HD treatment were randomly assigned to 2 groups in a 3-period 2-treatment design with low flux (A)--high flux (B)--low flux (A) for group I and B-A-B for group II, 6 weeks each period. The following parameters were measured in pre- and postdialytic serum samples at baseline and the end of each period: total serum fluorescence, Nepsilon-carboxymethyllysine (CML), free and protein-bound pentosidine, tHcy, Cysta and DMG.\n There was increased removal of free pentosidine during high-flux HD treatment compared to low-flux HD treatment, attaining significance between the second and third treatment periods (group 1: 86.0 +/- 4.7% vs. 79.2 +/- 8.8%, p = 0.007; group II: 84.0 +/- 6.3% vs. 79.8 +/- 9.8%, p = 0.049 for high vs. low flux). The intradialytic reduction rates for total serum fluorescence, tHcy, Cysta, DMG did not differ between high- and low-flux HD treatment. Protein-bound pentosidine and CML did not decrease during the dialysis sessions, neither with high-flux nor with low-flux HD membrane. Despite a strong decrease during single HD session, the predialytic levels of free pentosidine, tHcy, Cysta and DMG remained unchanged during the study period both for high- and low-flux HD treatment.\n The more pronounced effect of high-flux dialysis on the removal rate of free pentosidine, found in this randomized crossover study, could not translate into a significant difference in predialysis levels after a 6-week treatment period. We could not find any differences between polysulfone high- and low-flux membranes for lowering predialytic serum concentrations of the measured AGEs, which are mainly bound on albumin.", "Amyloidosis due to the retention of beta 2-microglobulin (beta 2-MG) is a frequent complication of hemodialysis (HD). Significant amounts of beta 2-MG can be removed from the body by highly permeable HD membranes, whereas conventional low-flux membranes are impermeable for the molecule. In a prospective and controlled study we investigated whether high-flux HD could delay the onset of dialysis-related amyloidosis (DRA). Twenty patients treated with cuprophane low-flux HD membranes were matched for age and previous time on HD either to continue their HD regimen or to receive HD treatment with high-flux polysulfone membranes. For 6 years each patient was examined for manifestations of DRA once a year or upon individual needs, additionally, serum beta 2-MG levels were monitored. After 6 years of follow-up no clinical signs of DRA were found in any of the patients dialyzed with high-flux polysulfone membranes, whereas 8/10 of the conventionally dialyzed patients had CTS and/or osteoarticular lesions. Serum levels of beta 2-MG were significantly reduced in patients treated with high-flux polysulfone membranes.", "Patients with diabetes and renal insufficiency (Db/ESRD), a group subject to accelerated atherosclerosis exhibit marked increases in the levels of circulating, glycation-derived reactive substances, termed advanced glycation endoproducts (AGEs). These products have been previously shown to react covalently with apoliprotein B (ApoB) to form AGE-ApoB, a modification that results in delayed low density lipoprotein (LDL) clearance and possibly to dyslipidemia. Because the effect of hemodialysis on AGE removal was shown to be unsatisfactory, based on single intradialytic studies, we examined the effect of long-term hemodialysis therapy on serum AGE-ApoB levels, as well as on total serum ApoB of 25 Db/ESRD patients treated by two types of hemodialysis filters, the Fresenius Inc. F8, as the low flux (LF), or high-flux polysulfone AN69 (HF) for two months using an AGE-specific ELISA. At the end of eight weeks, circulating AGE-ApoB levels were reduced significantly (by 35%) from baseline (P = 0.039) in patients treated by HF compared to a modest 16% reduction noted in patients treated by LF (P = 0.05) N = 12, P = 0.047). Of note, total plasma ApoB was reduced by 27% from baseline (P = 0.02) in patients treated by HF compared to a 6% reduction noted in those treated with LF (P = 0.8). In vitro comparison of AGE mass balance, and mass adsorption by the different filters revealed that the higher efficiency of HF filter was due to greater adsorption. The association of reduced AGE-ApoB levels with a decrease in total circulating ApoB by HF and not by LF dialysis suggests: (1) a causal link between AGE clearance and dyslipidemia in diabetic ESRD, and, (2) that more efficient modes of renal replacement treatment and AGE removal could significantly benefit clinical outcome.", "The objective was to evaluate the effect of high-flux hemodialysis on quality of life, intra- and interdialytic symptoms and neuropsychological function. The study was double-blind single cross-over with random allocation to order of treatment. The patients were stable adult hospital hemodialysis patients. Both the conventional and high-flux membranes were cellulose acetate, the dialysate was bicarbonate, and dialysate sodium was held constant. The high-flux membrane had an ultrafiltration rate of 15 ml/h/mm Hg transmembrane pressure, a B12 clearance of 88 ml/min and a beta 2-microglobulin clearance of 11.4 ml/min. The values of the conventional membrane were 3.5-5.0, 34-45 and negligible. Each treatment period was 4 months. Twenty-two patients completed both phases of the cross-over. The KT/V value was higher during high-flux than conventional treatment; 1.42 versus 1.27(p < 0.05). There were no differences between high-flux and conventional treatment with respect to quality of life. Symptoms during dialysis were less severe during high-flux than conventional treatment for 12/14 items. Only 3 items reached statistical significance (0.05 > p > 0.01) and none were clinically significant. Symptoms between dialyses were less severe during high-flux than conventional treatment for 18/20 items. No single item had a statistically significant improvement but 3 had clinically important improvement. Among the 23 neuropsychological variables, none demonstrated statistically significant changes.", "Hemodialysis is frequently complicated by hypotension and associated symptoms. It has been suggested that these symptoms may be related to the biochemical changes caused by cellulosic dialysis membranes. In this study, a prospective randomized crossover trial was conducted comparing the incidence of hypotension and acute symptoms during dialysis with large-surface-area (1.6 m2) cellulosic (cuprophane [CUP]) and noncellulosic (polyacrylonitrile [PAN], AN69) membranes. Dialyzers were used for a single use only. There was no difference in predialysis BUN, predialysis blood pressure, intradialytic weight gain, blood flow, dialysis efficiency (urea reduction), dialysis duration, hematocrit, or erythropoietin dose between the two study phases. When these clinical characteristics were matched, there was no difference in the number of episodes of hypotension (CUP, 19 +/- 3; PAN, 22 +/- 3; P = not significant [NS]). The incidence of symptomatic hypotension, as reflected by the number of episodes of hypotension requiring more than 100 mL of saline for correction, was also not different between study phases (CUP, 10 +/- 1; AN69, 11 +/- 2; P = NS). The incidence of intradialytic symptoms, including emesis, cramping, headache, angina, pruritus, and bronchospasm, was similar during the two study phases (CUP, 11 +/- 2; AN69, 10 +/- 1; P = NS). It was concluded that noncellulosic membranes do not offer any significant advantage over cellulosic membranes in reducing the acute complications of hemodialysis.", "Cardiovascular disease (CVD) is the leading cause of mortality in patients with end-stage renal disease (ESRD). The cornerstone of high CVD incidence in ESRD patients is endothelial dysfunction which results from inflammation, oxidative stress and insulin resistance. Although various modalities of hemodialysis (HD) have been presumed to exert different effects on oxidative stress and insulin resistance, solid evidence is still lacking.\n 40 ESRD patients undergoing HD were prospectively enrolled and divided randomly into two groups. Patients in each group received either F8 HPS (low-flux) (Group A) or FX80 (high-flux) (Group B) as HD dialyzers for 2 consecutive months. Diet pattern and medications were kept as usual in both groups to avoid considerable blood glucose change during study period. Blood samples were taken at the start and end of the study.\n A total of 38 patients (18 and 20 for Groups A and B, respectively) completed the study. Within each group, there was no change in adiponectin, plasma 8-iso-prostaglandin F(2)(alpha), high-sensitivity C-reactive protein, blood glucose and insulin after 2 months of treatment except a significant change of HOMA(IR) (p = 0.02) in high-flux group. The significant change of HOMA(IR) between the two groups (p = 0.017) mainly results from the parallel change of insulin between the two groups (p = 0.03).\n For patients receiving HD, the high-flux dialyzer with synthetic polysulfone membranes fails to provide a better anti-inflammatory or antioxidative effect than the low-flux dialyzer; however, the high-flux dialyzer does significantly improve insulin resistance in this short-term study. This result implies that the high-flux dialyzer might provide better cardiovascular protection than the low-flux dialyzer. Therefore, the low-flux dialyzer might be considered for patients who only need short-term HD therapy. Regarding patients under long-term maintenance HD therapy, a high-flux dialyzer might be the choice of dialyzer.\n Copyright 2008 S. Karger AG, Basel.", "We studied the influence of different modes of hemodialysis (HD) on plasma levels of beta 2-microglobulin (P-beta 2-m) and its correlation to changes in leukocyte count, complement activation (C3a), and elastase generation. The influence of dialyzer membrane, membrane surface area, duration of treatment, and blood flow was analyzed with respect to post-HD levels of P-beta 2-m. Twenty patients underwent 12 modes of bicarbonate hemodialysis in random order (n = 252) using three different membranes (Cuprophan [CU], hemophan [HE], or polyamide [PA], two dialyzer areas, and fast (400 mL/min) or slow (200 mL/min) blood flow (Qb) for 2 or 4 hours, respectively. All dialysate was collected and beta 2-m was analyzed (D-beta 2-m). After correction for hemoconcentration, P-beta 2-m concentrations were found to have decreased significantly during treatment with all three membranes (CU, 0.9 +/- 0.3 mg/L, P = 0.002; HE, 1.2 +/- 0.3 mg/L, P < 0.001; and PA, 8.3 +/- 0.3 mg/L, P < 0.001). Elimination of P-beta 2-m was influenced by type of membrane (P < 0.001) and ultrafiltration volume (P = 0.0019) but not by membrane area or Qb. The largest reduction in P-beta 2-m (-10.4 mg/L) was achieved by the following treatment combination: PA membrane, large dialyzer area, and low Qb for 4 hours. P-beta 2-m decreased more during PA dialysis at low Qb for 4 hours (-9.9 +/- 0.5 mg/L) than during high Qb for 2 hours (-6.8 +/- 0.5 mg/L, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "Uncontrolled studies have found that high-flux haemodialysis favourably modifies homocysteine and lipid profiles. We sought to confirm these findings by carrying out a randomized prospective comparison of high-flux and low-flux polysulphone in chronic, stable dialysis patients.\n Forty-eight patients were randomly assigned to either high or low-flux dialysis for 3 months. Serum levels of homocysteine, lipoprotein (a), and lipids were compared between the treatment groups at monthly intervals.\n All patient characteristics and laboratory variables were equally distributed between the groups at baseline. Over the study duration, we observed no differences between high- and low-flux treatment groups for the following outcomes: pre-dialysis homocysteine, lipoprotein (a), total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides (all P>0.05). Geometric mean (interquartile range) homocysteine at baseline was 20.0 (16.8-24.5) and 19.5 (15.3-22.0) micromol/l for the high-and low-flux groups respectively (P=0.80), and levels did not change significantly during the study. We did demonstrate a more pronounced intradialytic effect of high-flux dialysis on homocysteine levels, which fell during dialysis by 42%, compared to 32% with low-flux dialysis (P<0. 001).\n In this randomized controlled trial, the effects of high-flux and low-flux haemodialysis on homocysteine and lipid profiles were comparable. The greater intradialytic effect of high-flux dialysis on homocysteine did not translate into a significant difference in pre-dialysis levels after 3 months of study.", "The objective of this study was to evaluate the incidence of morbidity (at least one hospitalization) during the first twelve months of hemodialysis (thrice weekly for 4 hours) in 54 (27 males and 27 females) sex and age matched patients, of whom 32 were treated with AN 69 (M/F = 13/19, 62 +/- 14 years) and 22 with Cuprophan (M/F = 14/8, 61 +/- 14 years). Patients were classified according to the value of TAC urea during the period under study: constantly superior or equal to 20 mmol/liter in Group A (high TAC urea) or inferior to 20 mmol/liter in Group B (low TAC urea). Dialysis quantification (Kt/V) and estimation of the patient's protein catabolic rate (PCR) were based on measurement of the midweek pre- and post-dialysis blood urea nitrogen. In the patients of Group B, incidence of morbidity was significantly increased when age was over 50 years and when AN 69 membrane was used (P < 0.02). Furthermore, in Group A, the risk of hospitalization was significantly higher in patients treated by Cuprophan than in those treated by AN 69 (P < 0.02). The survival rate was also studied. Better survival (70%) at four years was observed in patients with high TAC urea who were treated by AN 69. The difference was highly significant with the survival rate (22%) in patients with high TAC urea who were treated by Cuprophan (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "Renal anemia significantly affects the morbidity and mortality of dialysis patients. The aim of the present study was to establish whether the severity of anemia and success of its treatment differs when using high-flux (HF) or low-flux (LF) hemodialysis. Twenty-five patients on long-term hemodialysis with a mean hematocrit (Hct) of 33%, S alb of 36 g/L, and Kt/V urea of 1.5 were divided into Groups X (n = 13) and Y (n = 12) in a prospective randomized crossover study. Group X was initially treated with LF hemodialysis to be followed by HF hemodialysis for 8 weeks each time. Group Y started with 8 week HF hemodialysis and continued, after crossover, with 8 weeks of LF hemodialysis. HF and LF hemodialysis were performed with polysulfone dialyzers F 7HPS and F60S (Fresenius Medical Care, Bad Homburg, Germany). Hct values, examined at 2 week intervals, did not differ significantly between Groups X and Y during 16 weeks of the study at any measuring interval. In another analysis, all results of HF hemodialysis (first 8 weeks of Y + second 8 weeks of X) were pooled as were all data of LF hemodialysis (first 8 weeks of X + second 8 weeks of Y). No significant relationships were noted between duration of treatment with HF hemodialysis and Hct (n = 72, rS = 0.11, p = 0.36) and between duration of LF hemodialysis and Hct (n = 74, rS = 0.02, p = 0.87) in the newly formed groups. The Hct measured during HF hemodialysis and LF hemodialysis did not differ significantly. Analysis of variance did not reveal a relationship between Hct and the HF or LF membrane. As HF and LF hemodialysis differed significantly in Kt/V urea, the variables were adjusted to identical Kt/V urea using analysis of covariance. No relationship between Hct and dialysis membrane permeability was demonstrated even in this case. Use of biocompatible LF and HF membranes in standard hemodialysis modes under conditions of adequate dose of dialysis and the time period studied did not result in different effects on anemia.", "The effect of high-flux hemodialysis membranes on patient survival has not been unequivocally determined. In this prospective, randomized clinical trial, we enrolled 738 incident hemodialysis patients, stratified them by serum albumin < or = 4 and >4 g/dl, and assigned them to either low-flux or high-flux membranes. We followed patients for 3 to 7.5 yr. Kaplan-Meier survival analysis showed no significant difference between high-flux and low-flux membranes, and a Cox proportional hazards model concurred. Patients with serum albumin < or = 4 g/dl had significantly higher survival rates in the high-flux group compared with the low-flux group (P = 0.032). In addition, a secondary analysis revealed that high-flux membranes may significantly improve survival of patients with diabetes. Among those with serum albumin < or = 4 g/dl, slightly different effects among patients with and without diabetes suggested a potential interaction between diabetes status and low serum albumin in the reduction of risk conferred by high-flux membranes. In summary, we did not detect a significant survival benefit with either high-flux or low-flux membranes in the population overall, but the use of high-flux membranes conferred a significant survival benefit among patients with serum albumin < or = 4 g/dl. The apparent survival benefit among patients who have diabetes and are treated with high-flux membranes requires confirmation given the post hoc nature of our analysis.", "Hyperhomocysteinaemia is a putative risk factor for atherothrombotic cardiovascular disease in the haemodialysis population. High-dose vitamin B therapy does not entirely normalize elevated plasma total homocysteine (tHcy) levels in haemodialysis patients. Alternative therapies to reduce tHcy further are therefore required. Modifications of the dialysis regimen may result in a better removal of Hcy. We examined the effect of dialyser membrane pore size on tHcy levels in vitamin-replete chronic haemodialysis patients.\n Forty-five haemodialysis patients were dialysed during 4 weeks with a low-flux, a high-flux and a super-flux membrane, in random order. Pre-dialysis tHcy was determined at baseline and every 4 weeks. In 18 patients, plasma tHcy before and after dialysis and dialysate tHcy concentrations were measured.\n Pre-dialysis tHcy decreased significantly during 4 weeks super-flux dialysis (-14.6 +/- 2.8%), whereas it remained stable during high-flux (+0.5 +/- 2.4%) and low-flux dialysis (+1.7 +/- 3.2%). The homocysteine reduction ratio was not different for the three membranes: 0.39 +/- 0.03 for the super-flux, 0.47 +/- 0.02 for the high-flux and 0.39 +/- 0.02 for the low-flux dialyser. The amount of Hcy recovered in the dialysate during a single dialysis session was also similar: 117.5 +/- 3.6 micro mol during super-flux, 95.3 +/- 11.5 micro mol during high-flux and 116.5 +/- 11.6 micro mol during low-flux dialysis.\n Super-flux dialysis significantly lowers tHcy in chronic haemodialysis patients. Improved removal of middle-molecule uraemic toxins with inhibitory effects on Hcy-metabolizing enzymes, rather than better dialytic clearance of Hcy itself, may explain the beneficial effect of the super-flux membrane.", "High-flux hemodialysis has been reported to attenuate renal dyslipidemia. To evaluate the contribution of dialysis membrane composition per se, we compared the impact on the lipoprotein profile of hemodialysis (HD) with a conventional cellulose dialysis membrane with that of a synthetic high-flux dialysis membrane in standard hemodialysis mode. Forty-two patients (24 men, 18 women; mean age, 69 years; range, 39-85 years) on maintenance HD with cellulosic dialysis membranes were randomized and stratified for diabetes mellitus to 12 weeks of HD treatment with either a cellulose acetate (CA; n = 23) or polyacrylonitrile (AN69; n = 19) membrane. HD was performed in a conventional low-flux standard HD mode 4-6 hours/session. Plasma levels of lipids (TC, TG), apolipoproteins (A-I, B, C-III, E), lipoprotein (a) (Ip(a)), and individual apoA and apoB containing lipoproteins (LP-A-I, LP-A-I:A-II, LP-B, LP-Bc) were determined. At baseline, the AN69 group had slightly higher plasma concentrations of apoC-III and C-III/HS, but there were no other differences at entry in study variables between the treatment groups. Twelve week treatment with an AN69 membrane did not result in any significant changes in lipoprotein profile compared with treatment with a cellulose acetate membrane. HD with AN69 dialysis membranes in the conventional low-flux standard hemodialysis mode does not affect the lipoprotein profile." ]

[ "11198658", "11816439", "8236401", "16088834", "18000538", "17046467", "11800303", "16776817" ]

[ "Randomized comparison of mefloquine-artesunate versus quinine in the treatment of multidrug-resistant falciparum malaria in pregnancy.", "Randomized comparison of quinine-clindamycin versus artesunate in the treatment of falciparum malaria in pregnancy.", "Spiramycin does not potentiate quinine treatment of falciparum malaria in pregnancy.", "A randomized comparison of artesunate-atovaquone-proguanil versus quinine in treatment for uncomplicated falciparum malaria during pregnancy.", "A randomized controlled pilot trial of azithromycin or artesunate added to sulfadoxine-pyrimethamine as treatment for malaria in pregnant women.", "Efficacy, safety, and tolerability of amodiaquine plus sulphadoxine-pyrimethamine used alone or in combination for malaria treatment in pregnancy: a randomised trial.", "Randomized trial of artesunate and mefloquine in comparison with quinine sulfate to treat P. falciparum malaria pregnant women.", "Therapeutic efficacy of sulphadoxine-pyrimethamine and chloroquine for the treatment of uncomplicated malaria in pregnancy in Burkina Faso." ]

[ "Since no effective malaria prevention measures have been identified for pregnant women living on the western border of Thailand, prompt diagnosis and efficient treatment are paramount, although drug resistance in Plasmodium falciparum has narrowed the treatment options. An open randomized comparison of supervised quinine (10 mg salt/kg every 8 h) for 7 days (Q7) versus mefloquine 25 mg base/kg (total dose) plus artesunate 4 mg/kg per day for 3 days (MAS3) was conducted in 1995-97 in 108 Karen women with acute uncomplicated falciparum malaria in the second or third trimesters of pregnancy. The MAS3 regimen was more effective than the Q7 regimen: day 63 cure rates were 98.2% (95% CI 94.7-100) (n = 65) for MAS3 and 67.0% (95% CI 43x3-90x8) (n = 41) for Q7, P = 0x001. The MAS3 regimen was also associated with less gametocyte carriage; the average person-gametocyte-weeks for MAS3 was 2.3 (95% CI 0-11) and for Q7 was 46x9 (95% CI 26-78) per 1000 person-weeks, respectively (P < 0.001). MAS3 was significantly better tolerated. These evident advantages must be balanced against a possible increased risk of stillbirth with the use of mefloquine in pregnancy. Further randomized studies assessing the safety and efficacy of other artemisinin-containing combination regimens in pregnancy are needed urgently.", "In areas where multidrug-resistant Plasmodium falciparum (MDR-Pf) is prevalent, only quinine is known to be safe and effective in pregnant women. On the western border of Thailand, 7 days of supervised quinine (30 mg/kg daily) cures two-thirds of P. falciparum-infected women in the 2nd and 3rd trimesters of pregnancy. Artesunate is effective against MDR-Pf and the limited data on its use in pregnancy suggest it is safe. An open randomized comparison of supervised quinine (10 mg salt/kg every 8 h) in combination with clindamycin (5 mg/kg every 8 h) for 7 days (QC7) versus artesunate 2 mg/kg per day for 7 days (A7) was conducted in 1997-2000 in 129 Karen women with acute uncomplicated falciparum malaria in the 2nd or 3rd trimesters of pregnancy. There was no difference in the day-42 cure rates between the QC7 (n = 65) and A7 (n = 64) regimens with an efficacy of 100% in both, confirmed by parasite genotyping. The A7 regimen was also associated with less gametocyte carriage; the average person-gametocyte-weeks for A7 was 3 (95% CI 0-19) and for QC7 was 39 (95% CI 21-66) per 1000 person-weeks, respectively (P < 0.01). There was no difference in gastrointestinal symptoms between the groups but there was significantly more tinnitus in the QC7 group compared to the A7 group (44.9% vs 8.9%; RR 5.1; 95% CI 1.9-13.5; P < 0.001). The favourable results with quinine-clindamycin mean that there is a useful back-up treatment for women with falciparum malaria who experience quinine and artesunate failures in pregnancy. Adherence to the 7-day regimen and cost (US$18.50 per treatment) are likely to be the main obstacles to this regimen.", "nan", "There is no safe, practical, and effective treatment for pregnant women infected with multidrug-resistant Plasmodium falciparum.\n We recruited pregnant Karen women in the second or third trimesters of pregnancy who had uncomplicated falciparum malaria for a randomized, open-label trial with a restricted sequential trial design of 7 days of supervised quinine (SQ7) versus 3 days of artesunate-atovaquone-proguanil (AAP).\n Eight-one pregnant women entered the study between December 2001 and July 2003; 42 were treated with SQ7 and 39 were treated with AAP. Fever, parasite clearance, and duration of anemia were significantly better with AAP; the treatment failure rate was 7 times lower (5% [2/39] vs. 37% [15/41]; relative risk, 7.1 [95% confidence interval, 1.7-29.2]; P = .001). There were no significant differences in birth weight, duration of gestation, or congenital abnormality rates in newborns or in growth and developmental parameters of infants monitored for 1 year.\n AAP is a well-tolerated, effective, practical, but expensive treatment for multidrug-resistant falciparum malaria during the second or third trimesters of pregnancy. Despite the small number of subjects, our results add to the growing body of evidence that AAP is safe for the mother and the fetus.", "New anti-malarial regimens are urgently needed in sub-Saharan Africa because of the increase in drug resistance. We investigated the safety and efficacy of azithromycin or artesunate combined with sulfadoxine-pyrimethamine used for treatment of malaria in pregnant women in Blantyre, Malawi.\n This was a randomized open-label clinical trial, conducted at two rural health centers in Blantyre district, Malawi. A total of 141 pregnant women with uncomplicated Plasmodium falciparum malaria were recruited and randomly allocated to 3 treatment groups: sulfadoxine-pyrimethamine (SP; 3 tablets, 500 mg sulfadoxine and 25 mg pyrimethamine per tablet); SP plus azithromycin (1 g/dayx2 days); or SP plus artesunate (200 mg/dayx3 days). Women received two doses administered at least 4 weeks apart. Heteroduplex tracking assays were performed to distinguish recrudescence from new infections. Main outcome measures were incidence of adverse outcomes, parasite and fever clearance times and recrudescence rates. All treatment regimens were well tolerated. Two women vomited soon after ingesting azithromycin. The parasite clearance time was significantly faster in the SP-artesunate group. Recrudescent episodes of malaria were less frequent with SP-azithromycin [Hazard Ratio 0.19 (95% confidence interval 0.06 to 0.63)] and SP-artesunate [Hazard Ratio 0.25 (95% confidence interval 0.10 to 0.65)] compared with SP monotherapy. With one exception (an abortion in the SP-azithromycin group), all adverse pregnancy outcomes could be attributed to known infectious or obstetrical causes. Because of the small sample size, the effect on birth outcomes, maternal malaria or maternal anemia could not be evaluated.\n Both SP-artesunate and SP-azithromycin appeared to be safe, well tolerated and efficacious for the treatment of malaria during pregnancy. A larger study is needed to determine their safety and efficacy in preventing poor birth outcomes.\n ClinialTrials.gov NCT00287300.", "The widespread increase in resistance of Plasmodium falciparum to chloroquine and sulphadoxine-pyrimethamine threatens the use of these drugs for malaria treatment in pregnancy. We aimed to assess the safety and efficacy of amodiaquine alone or in combination with sulphadoxine-pyrimethamine as alternative regimens.\n Pregnant women with a gestational age of 16 weeks or more who attended antenatal clinics at a district hospital in Ghana were screened for malaria with OptiMAL dipsticks. 900 pregnant women who had a positive test result and P falciparum asexual stage parasitaemia were enrolled and randomly assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, or amodiaquine plus sulphadoxine-pyrimethamine. The primary outcome was parasitological failure by day 28 of treatment. Women were seen on days 3, 7, 14, and 28 after the start of treatment to assess the effect of treatment on peripheral parasitaemia, haemoglobin concentration, white-blood-cell count, and liver function. Additionally, reports of adverse effects were solicited and monitored during follow-up visits. Analysis was by intention to treat. This trial is registered with the US National Institute of Health clinical trials database number NCT00131703.\n PCR-corrected parasitological failure by day 28 was 14%, 11%, 3%, and 0% in the women assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, and amodiaquine plus sulphadoxine-pyrimethamine, respectively (p<0.0001). No serious liver toxic effects or white-blood-cell dyscrasias were noted. Minor side-effects were reported more often on day 3 by women receiving amodiaquine (86%) or amodiaquine plus sulphadoxine-pyrimethamine (90%) than those receiving sulphadoxine-pyrimethamine (48%) or no antimalarial drugs (34%; p<0.0001 for every comparison).\n Amodiaquine alone or in combination with sulphadoxine-pyrimethamine, although associated with minor side-effects, is effective when used to treat malaria in pregnancy.", "To compare the effectiveness and safety of quinine sulfate and artesunate with mefloquine for treating second trimester pregnancy in women who suffered from Plasmodium falciparum malaria. The prospective study was done in Srisangwal Hospital, Mae Hong Son, Thailand. Sixty, second to third trimester pregnant patients with P. falciparum infection, were recruited at random. They received either quinine sulfate 10 mg/kg/day for at least 7 days, 29 women (group I), or oral artesunate 2 mg/kg as the first dose, 1 mg/kg every 12 hours orally for at least 5 days together with split doses of mefloquine, 15 mg/kg and 6 hours later 10 mg/kg orally 1 day after artesunate was stopped, 28 women (group II). Three cases (5%) were lost to follow-up before delivery, one case in group I and two cases in group II. After treatment, the mean hematocrit of group I was significantly less than group II (p = 0.000). The PCT (parasite clearance time) and FCT (fever clearance time) of group II were significantly shorter than group I (p = 0.000). None of the patients in both groups had recrudescences within 28 days. Group I had more adverse effects than group II. No adverse neurological effects in pregnancy were found in both groups. The calcification of placenta and IUGR (Intrauterine growth retard) were not different between the two groups (p = 0.964, 0.363 respectively). The PCT was not different between the calcified placenta group and normal placenta group (p = 0.058), but the TTPP (Total time of parasite presentation) was (p = 0.000). TTPP related to low birth weight and low apgar score at 1 minute might be the cause (p = 0.000, 0.000 F = 5.261, 21.627 respectively). TTPP and PCT related to neonatal blood pH and caused low neonatal blood pH (p = 0.000, 0.001 F = 24.351, 11.162 respectively). The physical and neurological development of the babies at 2, 4, 6 and 12 months follow-up, were normal and there were no congenital abnormalities in either group. TTPP relating to fetal outcome, the longer the TTPP, the worse the fetal outcome, so we should diagnose early and treat P. falciparum malaria in pregnancy to prevent fetal jeopardy. Artesunate with mefloquine could shorten the PCT more than quinine sulfate in pregnancy, so the fetal outcome was better than that of quinine sulfate. In cases of prolonged infection before treatment, artesunate might be the alternative treatment of P. falciparum malaria in pregnancy. However, its safety should be carefully studied further with a larger sample size.", "A reduction in the therapeutic efficacy of chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) has recently been observed in Burkina Faso. As these two drugs are used in pregnancy, their efficacy in pregnant women was studied to directly assess the level of drug resistance in this specific population, rather than to extrapolate results of studies conducted in children < 5 years of age.\n During the malaria transmission season of 2003 in Ouagadougou, the clinical efficacy of SP and CQ, using the WHO 28-day protocol, was assessed in primigravidae and secundigravidae presenting with uncomplicated malaria.\n PCR-corrected results by day 28 showed that among 62 women treated with SP, eight (12.9%) experienced late parasitological failure, but no clinical failures. Among 60 women treated with CQ, the overall failure rate was 46.7% including 1.7% early treatment failures, 5% late clinical failures and 40% late parasitological failures. SP induced a haemoglobin gain of 0.3 g/dL by day 14 and 0.9 g/dL by day 28. Treatment responses were independent of gravidity, gestational age and prior antenatal care visits.\n While CQ should no longer be used, the efficacy of SP is still compatible with use for intermittent preventive treatment (IPT) in pregnancy. However, given the possible spread of resistance, the drug should be restricted in its use." ]

[ "16539087", "9083732", "10402622", "12175355", "8514312", "14499168" ]

[ "Consumer involvement in consent document development: a multicenter cluster randomized trial to assess study participants' understanding.", "Development and evaluation of written patient information for endoscopic procedures.", "Effects of client interviewers on client-reported satisfaction with mental health services.", "Patient-controlled analgesia: what information does the patient want?", "Comparison of patient and staff surveys of consumer satisfaction.", "Does deliberation make a difference? Results from a citizens panel study of health goals priority setting." ]

[ "Despite widespread agreement on the importance of informed consent in clinical research, uncertainty remains about the adequacy of current consent procedures and documentation.\n The objective of the study was to compare an informed consent document developed by a consumer group of potential study participants to one developed by the study investigators. The study was a cluster randomized, controlled study embedded in a 'parent' randomized controlled trial of 1092 participants with Gulf War veterans' illnesses recruited in 1999-2000 at 20 US medical centers. Centers were randomized to the investigator-developed or participant-developed consent document. The primary outcome measure was an Informed Consent Questionnaire-4 (ICQ-4), a validated four-item scale measuring self-reported participant understanding scored from 0 to 1. Secondary outcomes included the Client Satisfaction Questionnaire-8 and measures of study refusal and adherence to the parent trial protocol.\n There were no significant differences between consent documents on the ICQ-4 score overall or at any of the time points. Mean (95% CI) treatment differences ranged from +0.020 (-0.015, 0.055) (better understanding) at entry to -0.021 (-0.054, 0.012) (worse understanding) at three-months for the participant versus the investigator document group. There were also no significant differences in satisfaction, adherence to the protocol, or in the proportion of patients who refused to participate in the trial.\n The consumer group may not have been representative of the study participants and they did not suggest dramatic changes to the consent document. The outcome assessment questionnaire was not validated prior to the trial's initiation.\n Consumer modification of the consent document did not lead to either benefit or harm in understanding, satisfaction, or study refusal and adherence rates. This study did demonstrate, however, that embedding consent studies in a clinical trial is feasible and can address important questions about informed consent without disrupting the primary study.", "In the process of revising our written patient information, we wanted to incorporate some patient feedback into the text, and to compare the new brochures with the old one in terms of procedure-related anxiety and general patient satisfaction.\n A total of 136 patients were asked about their present sources of information and issues they would like more information on. New brochures were developed for upper endoscopy, colonoscopy, and endoscopic retrograde cholangiopancreatography (ERCP), and 235 consecutive patients were then randomized to receive either the new brochures or the old one. Before the endoscopy procedure, the patients' sources of information, level of anxiety (on a five-point Likert scale) and general satisfaction with the written information was assessed. In addition, 89 patients completed a similar questionnaire after completing the endoscopic procedure, recording their degree of anxiety and discomfort during the procedure, and the appropriateness of the written information they had received.\n The written brochure was regarded as providing important information by 79% of the patients, while only 31% felt they had received important information from their referring doctor. The general level of anxiety was 2.0 (slightly anxious) with both brochures, with a mean score of 2.1 and 1.9 for the old brochure and the new one, respectively (P = 0.04). Previous endoscopy, male sex and high age were associated with a lower anxiety score. The post-endoscopy response indicated that the patients had received a realistic description of the procedure. The new brochures were rated as \"excellent\" or \"very good\" by 87% of the respondents.\n We have developed a new set of information brochures which appear to serve the purpose of providing adequate information, without causing patients undue anxiety.", "A study at two outpatient facilities compared two methods of collecting data on client satisfaction with mental health services provided by case managers and by physicians. A satisfaction survey instrument was developed with input from clients. A total of 120 clients were randomly assigned to be interviewed by either a staff member or a client. Clients from both facilities reported high levels of satisfaction regardless of the type of interviewer. Clients gave a significantly greater number of extremely negative responses when they were interviewed by client interviewers. No difference between the two groups was found in overall satisfaction with services received from case managers or physicians.", "To formulate and evaluate an information leaflet for patients using patient-controlled analgesia (PCA), incorporating information thought to be important by patients.\n The benefit of current information leaflets, written by professionals, has not been studied and their value to patients is unknown.\n Previous studies have shown that information leaflets were poorly designed and written in language too difficult for patients to understand.\n Seven focus groups were conducted to establish what information patients wanted to know about PCA. This information was incorporated into a new information leaflet. One hundred patients were randomized to receive either the new leaflet or the old leaflet in current use. A questionnaire was used to establish whether the new leaflet was more clear and informative than the old one.\n Patients wanted to know that the drug used in PCA was morphine. They wanted more information about side-effects, needed to be reassured that it was safe, and that they could not overdose or become addicted. They wanted detailed instructions and diagrams about the technique. The questionnaire study established that the new leaflet was clearer and more informative.\n Patients' contribution led to major change, producing a leaflet which was clearer, more attractive, more informative and which proved more satisfactory to patients.", "nan", "How to involve the public in setting health and health care priorities is a constant challenge for health system decisions. Policy maker interest in involving the public in increasingly complex and value-laden priority setting processes has led to the use of deliberative public involvement methods designed to promote discussion and debate among participants with the objective of obtaining more informed and consensual views. These methods have not been evaluated rigorously using controlled designs with pre- and post-test measurements. We examined, using a controlled design, the effects of introducing different opportunities for deliberation into a process for obtaining public input into a community health goals priority setting process. Our findings indicate that deliberation does make a difference to participant views. As more deliberation is introduced, participant views may be more amenable to change. Deliberation also offers the potential for views to become more rather than less entrenched. While we are beginning to understand the difference deliberation makes to participant views, we are still at an early stage in understanding the process through which these differences come about and what difference deliberation makes to broader outcomes such as civic competence, civic engagement and health policy decisions." ]

[ "20943705", "17457441", "19131401", "9866064", "11209540", "15817582", "15037402", "16518579", "18973893" ]

[ "Low-dose aspirin therapy and hypertensive pregnancy complications in unselected IVF and ICSI patients: a randomized, placebo-controlled, double-blind study.", "Effect of low-dose aspirin therapy on implantation rate in women undergoing in-vitro fertilization cycles.", "Does low-dose aspirin improve pregnancy rate in IVF/ICSI? A randomized double-blind placebo controlled trial.", "A matched study to determine whether low-dose aspirin without heparin improves pregnancy rates following frozen embryo transfer and/or affects endometrial sonographic parameters.", "Low-dose aspirin does not increase implantation rates in patients undergoing intracytoplasmic sperm injection: a prospective randomized study.", "Low-dose aspirin does not improve ovarian responsiveness or pregnancy rate in IVF and ICSI patients: a randomized, placebo-controlled double-blind study.", "Adjuvant low-dose aspirin therapy in poor responders undergoing in vitro fertilization: a prospective, randomized, double-blind, placebo-controlled trial.", "Does addition of low-dose aspirin and/or steroid as a standard treatment in nonselected intracytoplasmic sperm injection cycles improve in vitro fertilization success? A randomized, prospective, placebo-controlled study.", "Low-dose aspirin in non-tubal IVF patients with previous failed conception: a prospective randomized double-blind placebo-controlled trial." ]

[ "Low-dose aspirin therapy could improve remodelling of maternal spiral arteries during early placentation and prevent subsequent pregnancy-related hypertensive disorders. We investigated whether low-dose aspirin therapy reduces the incidence of hypertensive pregnancy complications in unselected IVF and ICSI patients when medication was started prior to pregnancy.\n A total of 487 patients who underwent IVF/ICSI were randomized to receive 100 mg aspirin (n = 242) or placebo (n = 245) daily, starting on the first day of gonadotrophin stimulation. Pregnant women continued the medication until delivery. A total of 107 patients (52 with aspirin and 55 with placebo) experienced live birth and were included in this follow-up study. The main outcome measure was the incidence of hypertensive pregnancy complications.\n Embryo transfer took place in 227 (94%) women in the aspirin group and in 229 (93%) women in the placebo group. The live birth rate between the aspirin (22.9%) and placebo (24.0%) groups did not differ significantly (P = 0.78). The overall incidence of hypertensive pregnancy complications was 15.4% (8/52) in the aspirin group and 18.2% (10/55) in the placebo group (P = 0.70, 95% confidence interval for the difference of proportions -17 to 11%). There were two cases of severe pre-eclampsia in the aspirin group and three cases in the placebo group.\n In the present study, the incidence of hypertensive pregnancy complications did not differ statistically significantly between low-dose aspirin and placebo groups in unselected IVF/ICSI patients, when medication was started concomitantly with gonadotrophin stimulation and continued until delivery. The study was registered at clinicaltrials.gov. NCT00683202.", "To determine the effect of low-dose aspirin on ovarian response, implantation and pregnancy rates in patients undergoing in-vitro fertilization (IVF) cycles.\n We performed a randomized analysis of 145 infertile women with a mean+/-SD age of 29.6 +/- 4.47 years who underwent cycles of IVF. Patients received 100 mg of aspirin (n=72) or placebo (n=73) daily. This study was conducted in Royan Institute, Tehran, Iran from April 2002 to January 2004. Aspirin was started on the 21st of their preceding menstrual cycle and it was continued until menstruation or a negative pregnancy test. Pregnant women received the medication until 12 weeks of pregnancy. The main outcome measures were number of follicles >or=15 mm, number of oocytes retrieved, serum E2 levels, cancellation rate, Ovarian Hyperstimulation Syndrome (OHSS) occurrence, number of embryos transferred, and implantation and pregnancy rates.\n There were statistically significant differences between the treatment group and the control group in the number of follicles (7.4 +/- 4.1 versus 9.0 +/- 4.8) and OHSS occurrence (5.6% versus 23.3%) but not in the other measures.\n The addition of aspirin low dose (100 mg/daily) to the standard long protocol for oocyte retrieval did not improve implantation and pregnancy rates in unselected patients undergoing IVF cycles.", "It has been suggested in the literature that low-dose aspirin leads to an increased number of oocytes in IVF/ICSI as well as a higher pregnancy rate. The aim of the present study was to investigate the effect of daily administration of low-dose aspirin, compared with placebo, on pregnancy rate in IVF and ICSI.\n This study was a prospective, randomized, double-blind placebo controlled trial, performed in the fertility centre of the University Hospital of Ghent. Concealed allocation by computerized randomization was done by the central pharmacy of the hospital. Daily oral administration of aspirin 100 mg or placebo started before stimulation and was continued until confirmation of pregnancy by detection of fetal heart activity on ultrasound. The primary outcome measure assessed in this trial was clinical pregnancy rate per cycle.\n Two hundred and one couples were included in this study, 193 women (aspirin group n = 97, placebo group n = 96) started treatment and 181 underwent an embryo transfer. There were 31 clinical pregnancies (31/97 or 32%) in the aspirin group versus 30 (30/96 or 31%; P = 0.916; OR 1.033; 95% CI 0.565-1.890) in the placebo group.\n This randomized controlled trial could not show a significant difference in clinical pregnancy rate between the aspirin and the placebo group in a first or second IVF/ICSI cycle. Given the lack of evidence for a beneficial effect of low-dose aspirin, it appears that low-dose aspirin should not be prescribed routinely in IVF/ICSI treatment. ClinicalTrials.gov Identifier: NCT00644085.", "The objective of the matched, controlled study was to determine whether low-dose aspirin therapy without heparin improves pregnancy rates following frozen embryo transfer.\n Thirty-six women who did not achieve a pregnancy following fresh embryo transfer and who had frozen embryos available for another transfer were included. Eighteen women were treated with 81 mg aspirin from day 2 of the cycle through pregnancy testing. If the beta-human chorionic gonadotropin level was positive, aspirin was continued through the pregnancy. Eighteen women were not given aspirin. The mean outcome variables were pregnancy and implantation rates.\n The clinical pregnancy rate in the aspirin group was 11.1%, compared with 33.3% for the controls, and implantation rates were 2.9 and 10.9%, respectively.\n No positive effects of low-dose aspirin therapy on pregnancy rates following frozen embryo transfer were observed.", "The aim was to evaluate the effect of aspirin on pregnancy and implantation rates in an unselected group of patients undergoing intracytoplasmic sperm injection (ICSI).\n Two hundred and seventy-nine patients were randomized to receive 80 mg of aspirin (n = 139) or no treatment (r = 136) starting from the first day of controlled ovarian hyperstimulation.\n Duration of stimulation, gonadotropin consumption, peak estradiol, number of oocytes retrieved, fertilization rate, cleavage rate, and number of embryos transferred were similar in the two groups. Implantation and clinical pregnancy rates were 15.6% and 39.6% versus 15.1% and 43.4% in aspirin treated and untreated groups, respectively (P > 0.05).\n Low-dose aspirin administration does not improve implantation and pregnancy rates in an unselected group of patients undergoing ICSI.", "Poor ovarian and endometrial responses to gonadotrophin stimulation in assisted reproduction techniques lead to decreased pregnancy rates. The aim of the present study was to test the hypothesis that low-dose aspirin started prior to controlled ovarian stimulation improves ovarian responsiveness, pregnancy rate (PR) and pregnancy outcome.\n A total of 374 women who were to undergo IVF/ICSI were randomized to receive 100 mg of aspirin (n=186) or placebo (n=188) daily. Treatment was started on the first day of controlled ovarian stimulation. It was continued until menstruation or a negative pregnancy test. Pregnant women continued the medication until delivery. The main outcome measures were the number of oocytes, number and quality of embryos, the clinical PR and pregnancy outcome.\n The mean (+/-SD) number of oocytes (12.0+/-7.0 versus 12.7+/-7.2), the total mean number of embryos (5.82+/-4.35 versus 5.99+/-4.66), the mean number of top quality embryos (0.99+/-1.39 versus 1.18+/-1.51) and the number of embryos transferred (1.64+/-0.64 versus 1.63+/-0.71) did not differ in the aspirin and placebo groups. Between the aspirin and placebo group, there was no statistically significant difference in clinical PR per embryo transfer (25.3%, n=44 out of 174 versus 27.4%, n=48 out of 175) or clinical PR per cycle initiated (23.7% versus 25.5%). Birth rate per embryo transfer did not differ significantly between the aspirin (18.4%) and placebo (21.1%) groups. The incidence of poor responders [12 (6.5%) versus 13 (6.9%)] was similar in both groups.\n The present results indicate that low-dose aspirin treatment does not have any beneficial effect on ovarian responsiveness, PR and pregnancy outcome in unselected women undergoing IVF/ICSI.", "To evaluate the effect of adjuvant low-dose aspirin on utero-ovarian blood flow and ovarian responsiveness in poor responders undergoing IVF.\n Prospective randomized, double-blind, placebo-controlled study.\n University-affiliated teaching hospital.\n Sixty patients classified as poor responders undergoing IVF.\n Supplementation with low-dose aspirin (80 mg daily) or placebo to a long down-regulation protocol.\n Doppler measurement of intraovarian and uterine pulsatility index was performed before (baseline) and after ovarian stimulation (day of hCG administration). Duration of use and dose of gonadotropins, cycle cancellation rate, number of mature follicles recruited, and oocytes retrieved were also measured.\n High cancellation rates were found in both groups (33.3% vs. 26.7%, placebo vs. treatment). There were no significant differences in total dose of hMG used (66 vs. 57 hMG, 75 IU ampules), median number of mature follicles recruited (3.5 vs. 3.0), or median number of oocytes retrieved (4 vs. 3). No significant differences were found in either intraovarian or uterine artery pulsatility index measured at baseline or on the day of hCG administration.\n Supplementation with low-dose aspirin failed to improve either ovarian and uterine blood flow or ovarian responsiveness in poor responders undergoing IVF.", "To investigate the effects of short-term low-dose aspirin and/or steroid use on implantation and pregnancy rates in nonselected intracytoplasmic sperm injection (ICSI) cycles.\n Two-hundred patients undergoing ICSI for their first cycle were enrolled in this study. Participants were then randomized into four groups on the embryo transfer day. Aspirin (100 mg/day) in group A, prednisolone (10 mg/day) in group B, aspirin along with prednisolone in group C were given while placebo was administrated to group D.\n There were no statistically significant differences recorded in the demographic, ovulation induction cycle characteristics between groups. Mean transferred embryo number and mean top quality embryo number were similar among study groups. There were no statistical differences in implantation and pregnancy rates between study groups.\n Administration of low-dose aspirin and prednisolone alone or concomitant as a standard treatment have no positive effects on implantation and/or pregnancy rates.", "To analyze whether the administration of low-dose aspirin during IVF treatment improves the uterine blood flow and improves ongoing pregnancy rates for non-tubal factor IVF patients with previous failed conception.\n Prospective double-blind placebo-controlled trial.\n University fertility clinic.\n Non-tubal IVF patients with previous failed conception.\n Daily 100 mg aspirin or placebo throughout an IVF treatment with a long GnRH-agonist stimulation protocol.\n Ongoing pregnancy rate, pulsatility index of the uterine artery.\n Of 169 patients, 84 were assigned to aspirin treatment and 85 to placebo treatment. In the aspirin group, 28 patients (35.4%) had an ongoing pregnancy, and in the placebo group, 26 patients (31.0%) had an ongoing pregnancy. Multilevel analyses showed that the pulsatility index of the uterine artery was not affected by aspirin or placebo treatment.\n Low-dose aspirin administration during IVF treatment does not improve pregnancy rates of non-tubal factor IVF patients with previous failed conception, and it does not affect the arterial uterine blood flow." ]

[ "21114607", "20380655", "19317822", "20722676", "21307137", "18782641", "20580422", "19366970", "19592625", "20609969", "18931095", "19688338", "19515413", "20417856", "19289857", "20536952" ]

[ "Liraglutide provides similar glycaemic control as glimepiride (both in combination with metformin) and reduces body weight and systolic blood pressure in Asian population with type 2 diabetes from China, South Korea and India: a 16-week, randomized, double-blind, active control trial(*).", "Improved glycaemic control with minimal hypoglycaemia and no weight change with the once-daily human glucagon-like peptide-1 analogue liraglutide as add-on to sulphonylurea in Japanese patients with type 2 diabetes.", "Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU).", "Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial.", "DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes.", "Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study.", "Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial.", "Treatment with the human once-weekly glucagon-like peptide-1 analog taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes inadequately controlled with metformin alone: a double-blind placebo-controlled study.", "Potential of albiglutide, a long-acting GLP-1 receptor agonist, in type 2 diabetes: a randomized controlled trial exploring weekly, biweekly, and monthly dosing.", "Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial.", "Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study.", "Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.", "Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6).", "Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial.", "Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD).", "Safety and tolerability of high doses of taspoglutide, a once-weekly human GLP-1 analogue, in diabetic patients treated with metformin: a randomized double-blind placebo-controlled study." ]

[ "To assess and compare the efficacy and safety of liraglutide with those of glimepiride, both in combination with metformin for the treatment of type 2 diabetes in Asian population from China, South Korea and India.\n A 16-week, randomized, double-blind, double-dummy, four-arm, active control trial was carried out. In total, 929 subjects with type 2 diabetes with a mean (±s.d.) age of 53.3 ± 9.5 years, HbA₁(c) of 8.6 ± 1.0% and body weight of 68.1 ± 11.7 kg were randomized (liraglutide 0.6, 1.2 or 1.8 mg once daily or glimepiride 4 mg once daily all in combination with metformin: 1 : 1 : 1 : 1). One subject withdrew immediately after randomization and before exposure.\n HbA₁(c) was significantly reduced in all groups compared with baseline. Treatment with liraglutide 1.2 and 1.8 mg was non-inferior to glimepiride (mean HbA₁(c) reduction: 1.36% points, 1.45% points and 1.39% points, respectively). No significant difference was shown in the percentage of subjects reaching American Diabetes Association HbA₁(c) target <7% or American Association of Clinical Endocrinologists target ≤6.5% between liraglutide 1.2 and 1.8 mg and glimepiride. Liraglutide was associated with a 1.8-2.4 kg mean weight reduction, compared with a 0.1 kg mean weight gain with glimepiride. Liraglutide led to a significantly greater reduction in systolic blood pressure (SBP) compared with glimepiride. Two subjects in the glimepiride group reported major hypoglycaemia while none in the liraglutide groups. Liraglutide was associated with about 10-fold lower incidence of minor hypoglycaemia than glimepiride. Gastrointestinal disorders were the most common adverse events (AEs) for liraglutide, but were transient and resulted in few withdrawals.\n In Asian subjects with type 2 diabetes, once-daily liraglutide led to improvement in glycaemic control similar to that with glimepiride but with less frequent major and minor hypoglycaemia. Liraglutide also induced a significant weight loss and reduced SBP and was generally well tolerated. The most frequently reported AE was transient nausea. The effect of liraglutide in this Asian population is comparable to the effects seen in Caucasian, African American and Hispanic populations in global liraglutide phase 3 trials.\n © 2010 Blackwell Publishing Ltd.", "Sulphonylureas (SUs) are often used as first-line treatments for type 2 diabetes in Japan, hence it is important to study new antidiabetic drugs in combination with SUs in Japanese patients.\n The efficacy and safety of the once-daily human glucagon-like peptide-1 (GLP-1) analogue liraglutide were compared in 264 Japanese subjects [mean body mass index (BMI) 24.9 kg/m(2); mean glycated haemoglobin (HBA1c) 8.4%] randomized and exposed to receive liraglutide 0.6 mg/day (n = 88), 0.9 mg/day (n = 88) or placebo (n = 88) each added to SU monotherapy (glibenclamide, glicazide or glimeprimide) in a 24-week, double-blind, parallel-group trial.\n The mean change in HBA1c from baseline to week 24 (LOCF) was -1.56 (s.d. 0.84) and -1.46 (s.d. 0.95) with liraglutide 0.9 and 0.6 mg respectively, and -0.40 (s.d. 0.93) with placebo. HBA1c decreased in the placebo group from 8.45 to 8.06%, while liraglutide reduced HBA1c from 8.60 to 7.14%, and from 8.23 to 6.67% at the 0.6 and 0.9 mg doses respectively. Mean HBA1c at week 24 of the two liraglutide groups were significantly lower than the placebo group (p < 0.0001 for both). More subjects reached HBA1c < 7.0% with liraglutide (0.6 mg: 46.5%; 0.9 mg: 71.3%) vs. placebo (14.8%). Fasting plasma glucose (FPG) levels were significantly improved with liraglutide (difference -1.47 mmol/l and -1.80 mmol/l with 0.6 and 0.9 mg vs. placebo; p < 0.0001). Overall safety was similar between treatments: no major hypoglycaemic episodes were reported, while 84/77/38 minor hypoglycaemic episodes occurred in the 0.6 mg/0.9 mg and placebo treatment groups (all in combination with SU), reflecting lower ambient glucose levels. No relevant change in mean body weight occurred in subjects receiving liraglutide (0.6 mg: 0.06 kg; 0.9 mg: -0.37 kg), while mean body weight decreased in subjects receiving placebo (-1.12 kg).\n The addition of liraglutide to SU treatment for 24 weeks dose-dependently improved glycaemic control vs. SU monotherapy, without causing major hypoglycaemia or weight gain or loss.", "To compare the effects of combining liraglutide (0.6, 1.2 or 1.8 mg/day) or rosiglitazone 4 mg/day (all n >or= 228) or placebo (n = 114) with glimepiride (2-4 mg/day) on glycaemic control, body weight and safety in Type 2 diabetes.\n In total, 1041 adults (mean +/- sd), age 56 +/- 10 years, weight 82 +/- 17 kg and glycated haemoglobin (HbA(1c)) 8.4 +/- 1.0% at 116 sites in 21 countries were stratified based on previous oral glucose-lowering mono : combination therapies (30 : 70%) to participate in a five-arm, 26-week, double-dummy, randomized study.\n Liraglutide (1.2 or 1.8 mg) produced greater reductions in HbA(1c) from baseline, (-1.1%, baseline 8.5%) compared with placebo (+0.2%, P < 0.0001, baseline 8.4%) or rosiglitazone (-0.4%, P < 0.0001, baseline 8.4%) when added to glimepiride. Liraglutide 0.6 mg was less effective (-0.6%, baseline 8.4%). Fasting plasma glucose decreased by week 2, with a 1.6 mmol/l decrease from baseline at week 26 with liraglutide 1.2 mg (baseline 9.8 mmol/l) or 1.8 mg (baseline 9.7 mmol/l) compared with a 0.9 mmol/l increase (placebo, P < 0.0001, baseline 9.5 mmol/l) or 1.0 mmol/l decrease (rosiglitazone, P < 0.006, baseline 9.9 mmol/l). Decreases in postprandial plasma glucose from baseline were greater with liraglutide 1.2 or 1.8 mg [-2.5 to -2.7 mmol/l (baseline 12.9 mmol/l for both)] compared with placebo (-0.4 mmol/l, P < 0.0001, baseline 12.7 mmol/l) or rosiglitazone (-1.8 mmol/l, P < 0.05, baseline 13.0 mmol/l). Changes in body weight with liraglutide 1.8 mg (-0.2 kg, baseline 83.0 kg), 1.2 mg (+0.3 kg, baseline 80.0 kg) or placebo (-0.1 kg, baseline 81.9 kg) were less than with rosiglitazone (+2.1 kg, P < 0.0001, baseline 80.6 kg). Main adverse events for all treatments were minor hypoglycaemia (< 10%), nausea (< 11%), vomiting (< 5%) and diarrhoea (< 8%).\n Liraglutide added to glimepiride was well tolerated and provided improved glycaemic control and favourable weight profile.", "To evaluate the dose-response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes.\n Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA(1c)) > or = 7.0 and < 9.0% (> or = 53 and < 75 mmol/mol)] on metformin (> or = 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 microg once daily or twice daily or placebo. The primary end-point was change in HbA(1c) from baseline to 13 weeks in the intent-to-treat population.\n Lixisenatide significantly improved mean HbA(1c) from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 microg doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P < 0.01 vs. placebo). Target HbA(1c) < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 microg once-daily lixisenatide vs. 32% receiving placebo (P < 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from -2.0 to -3.9 kg with lixisenatide vs. -1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea.\n Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose-response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 microg once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies.", "We wanted to understand the effects of once-weekly vs. twice-daily glucagon-like peptide-1 receptor agonism for treatment of patients with type 2 diabetes.\n The objective of the study was to compare effects of exenatide once weekly (ExQW) and exenatide twice daily (ExBID) on glycemic control, body weight, and safety.\n This was a 24-wk, randomized, open-label, comparator-controlled study.\n The study was conducted at 43 sites in the United States.\n The study population was 252 intent-to-treat patients with type 2 diabetes [baseline (mean ± SD): glycosylated hemoglobin (HbA1c) 8.4 ± 1.2%, fasting plasma glucose 171 ± 47 mg/dl, weight 96 ± 20 kg] that were drug naïve (19%) or previously treated with one (47%) or multiple (35%) oral antidiabetic medications.\n Interventions included ExQW 2 mg for 24 wk or ExBID 5 μg for 4 wk followed by ExBID 10 μg for 20 wk.\n The change in HbA1c from baseline to wk 24 was measured.\n At 24 wk, ExQW produced significantly greater changes from baseline (least squares mean ± SE) vs. ExBID in HbA1c (-1.6 ± 0.1% vs. -0.9 ± 0.1%; P < 0.0001) and fasting plasma glucose (-35 ± 5 mg/dl vs. -12 ± 5 mg/dl; P = 0.0008). Similar reductions in mean body weight from baseline to wk 24 were observed in both groups (-2.3 ± 0.4 kg and -1.4 ± 0.4 kg). Both treatments were generally well tolerated. Transient and predominantly mild to moderate nausea, the most frequent adverse event, was less common with ExQW (14%) than with ExBID (35%). Injection-site reactions were infrequent, but more common with ExQW. No major hypoglycemia occurred.\n Continuous glucagon-like peptide-1 receptor agonism with ExQW resulted in superior glycemic control, with less nausea, compared with ExBID in patients with type 2 diabetes. Both groups lost weight.", "Exenatide is an incretin mimetic that shares glucoregulatory properties with glucagon-like peptide 1 (GLP-1), and improves glycaemic control, with progressive bodyweight reductions, when administered twice a day in patients with type 2 diabetes. We compared the efficacy of a once-weekly formulation of exenatide to that of a twice daily dose.\n A 30-week, randomised, non-inferiority study compared a long-acting release formulation of exenatide 2 mg administered once weekly to 10 mug exenatide administered twice a day, in 295 patients with type 2 diabetes (haemoglobin A(1c) [HbA(1c)] 8.3% [SD 1.0], mean fasting plasma glucose 9 [SD 2] mmol/L, weight 102 [SD 20] kg, diabetes duration 6.7 [SD 5.0] years). The patients were naive to drug therapy, or on one or more oral antidiabetic agents. The primary endpoint was the change in HbA(1c) at 30 weeks. This study is registered with ClinicalTrials.gov, number NCT00308139.\n At 30 weeks, the patients given exenatide once a week had significantly greater changes in HbA(1c) than those given exenatide twice a day (-1.9 [SE 0.1%] vs -1.5 [0.1%], 95% CI -0.54% to -0.12%; p=0.0023). A significantly greater proportion of patients receiving treatment once a week versus twice a day achieved target HbA(1c) levels of 7.0% or less (77%vs 61% of evaluable patients, p=0.0039).\n Exenatide once weekly resulted in significantly greater improvements in glycaemic control than exenatide given twice a day, with no increased risk of hypoglycaemia and similar reductions in bodyweight.", "Most patients with type 2 diabetes begin pharmacotherapy with metformin, but eventually need additional treatment. We assessed the safety and efficacy of once weekly exenatide, a glucagon-like peptide 1 receptor agonist, versus maximum approved doses of the dipeptidyl peptidase-4 inhibitor, sitagliptin, or the thiazolidinedione, pioglitazone, in patients treated with metformin.\n In this 26-week randomised, double-blind, double-dummy, superiority trial, patients with type 2 diabetes who had been treated with metformin, and at baseline had mean glycosylated haemoglobin (HbA(1c)) of 8.5% (SD 1.1), fasting plasma glucose of 9.1 mmol/L (2.6), and weight of 88.0 kg (20.1), were enrolled and treated at 72 sites in the USA, India, and Mexico. Patients were randomly assigned to receive: 2 mg injected exenatide once weekly plus oral placebo once daily; 100 mg oral sitagliptin once daily plus injected placebo once weekly; or 45 mg oral pioglitazone once daily plus injected placebo once weekly. Primary endpoint was change in HbA(1c) between baseline and week 26. Analysis was by intention to treat, for all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00637273.\n 170 patients were assigned to receive once weekly exenatide, 172 to receive sitagliptin, and 172 to receive pioglitazone. 491 patients received at least one dose of study drug and were included in the intention-to-treat analysis (160 on exenatide, 166 on sitagliptin, and 165 on pioglitazone). Treatment with exenatide reduced HbA(1c) (least square mean -1.5%, 95% CI -1.7 to -1.4) significantly more than did sitagliptin (-0.9%, -1.1 to -0.7) or pioglitazone (-1.2%, -1.4 to -1.0). Treatment differences were -0.6% (95% CI -0.9 to -0.4, p<0.0001) for exenatide versus sitagliptin, and -0.3% (-0.6 to -0.1, p=0.0165) for exenatide versus pioglitazone. Weight loss with exenatide (-2.3 kg, 95% CI-2.9 to -1.7) was significantly greater than with sitagliptin (difference -1.5 kg, 95% CI -2.4 to -0.7, p=0.0002) or pioglitazone (difference -5.1 kg, -5.9 to -4.3, p<0.0001). No episodes of major hypoglycaemia occurred. The most frequent adverse events with exenatide and sitagliptin were nausea (n=38, 24%, and n=16, 10%, respectively) and diarrhoea (n=29, 18%, and n=16, 10%, respectively); upper-respiratory-tract infection (n=17, 10%) and peripheral oedema (n=13, 8%) were the most frequent events with pioglitazone.\n The goal of many clinicians who manage diabetes is to achieve optimum glucose control alongside weight loss and a minimum number of hypoglycaemic episodes. Addition of exenatide once weekly to metformin achieved this goal more often than did addition of maximum daily doses of either sitagliptin or pioglitazone.\n Amylin Pharmaceuticals and Eli Lilly.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "To evaluate the efficacy and safety of taspoglutide (R1583/BIM51077), a human once-weekly glucagon-like peptide-1 analog, in patients with type 2 diabetes inadequately controlled with metformin.\n Type 2 diabetic (n = 306) patients who failed to obtain glycemic control (A1C 7-9.5%) despite 1,500 mg metformin daily were randomly assigned to 8 weeks of double-blind subcutaneous treatment with placebo or taspoglutide, either 5, 10, or 20 mg once weekly or 10 or 20 mg once every 2 weeks, and followed for 4 additional weeks. All patients received their previously established dose of metformin throughout the study. Glycemic control was assessed by change in A1C (percent) from baseline.\n Significantly greater (P < 0.0001) reductions in A1C from a mean +/- SD baseline of 7.9 +/- 0.7% were observed in all taspoglutide groups compared with placebo after 8 weeks of treatment: -1.0 +/- 0.1% (5 mg once weekly), -1.2 +/- 0.1% (10 mg once weekly), -1.2 +/- 0.1% (20 mg once weekly), -0.9 +/- 0.1% (10 mg Q2W), and -1.0 +/- 0.1% (20 mg Q2W) vs. -0.2 +/- 0.1% with placebo. After 8 weeks, body weight loss was significantly greater in the 10 mg (-2.1 +/- 0.3 kg, P = 0.0035 vs. placebo) and 20 mg (-2.8 +/- 0.3 kg, P < 0.0001) once-weekly groups and the 20 mg once every 2 weeks (-1.9 +/- 0.3 kg, P = 0.0083) group than with placebo (-0.8 +/- 0.3 kg). The most common adverse event was dose-dependent, transient, mild-to-moderate nausea; the incidence of hypoglycemia was very low.\n Taspoglutide used in combination with metformin significantly improves fasting and postprandial glucose control and induces weight loss, with a favorable tolerability profile.", "To evaluate the efficacy, safety, and tolerability of incremental doses of albiglutide, a long-acting glucagon-like peptide-1 receptor agonist, administered with three dosing schedules in patients with type 2 diabetes inadequately controlled with diet and exercise or metformin monotherapy.\n In this randomized multicenter double-blind parallel-group study, 356 type 2 diabetic subjects with similar mean baseline characteristics (age 54 years, diabetes duration 4.9 years, BMI 32.1 kg/m(2), A1C 8.0%) received subcutaneous placebo or albiglutide (weekly [4, 15, or 30 mg], biweekly [15, 30, or 50 mg], or monthly [50 or 100 mg]) or exenatide twice daily as an open-label active reference (per labeling in metformin subjects only) over 16 weeks followed by an 11-week washout period. The main outcome measure was change from baseline A1C of albiglutide groups versus placebo at week 16.\n Dose-dependent reductions in A1C were observed within all albiglutide schedules. Mean A1C was similarly reduced from baseline by albiglutide 30 mg weekly, 50 mg biweekly (every 2 weeks), and 100 mg monthly (-0.87, -0.79, and -0.87%, respectively) versus placebo (-0.17%, P < 0.004) and exenatide (-0.54%). Weight loss (-1.1 to -1.7 kg) was observed with these three albiglutide doses with no significant between-group effects. The incidence of gastrointestinal adverse events in subjects receiving albiglutide 30 mg weekly was less than that observed for the highest biweekly and monthly doses of albiglutide or exenatide.\n Weekly albiglutide administration significantly improved glycemic control and elicited weight loss in type 2 diabetic patients, with a favorable safety and tolerability profile.", "Diabetes treatments are needed that are convenient, provide effective glycaemic control, and do not cause weight gain. We aimed to test the hypothesis that improvement in haemoglobin A(1c) (HbA(1c)) achieved with once weekly exenatide was superior to that achieved with insulin glargine titrated to glucose targets.\n In this 26-week, open-label, randomised, parallel study, we compared exenatide with insulin glargine in adults with type 2 diabetes who had suboptimum glycaemic control despite use of maximum tolerated doses of blood-glucose-lowering drugs for 3 months or longer. Patients were randomly assigned to add exenatide (2 mg, once-a-week injection) or insulin glargine (once-daily injection, starting dose 10 IU, target glucose range 4.0-5.5 mmol/L) to their blood-glucose-lowering regimens. Randomisation was with a one-to-one allocation and block size four, stratified according to country and concomitant treatment (70% metformin only; 30% metformin plus sulphonylurea). Participants and clinical investigators were not masked to assignment, but investigators analysing data were. The primary endpoint was change in HbA(1c) from baseline, and analysis of this outcome was by modified intention to treat for all patients who received at least one dose of study drug. This trial is registered at ClinicalTrials.gov, number NCT00641056.\n 456 patients were randomly allocated to treatment and were included in the modified intention-to-treat analysis (233 exenatide, 223 insulin glargine). Participants who received at least one dose of study drug and for whom baseline and at least one postbaseline measurement of HbA(1c) were available were included in the primary efficacy analysis. Change in HbA(1c) at 26 weeks was greater in patients taking exenatide (n=228; -1.5%, SE 0.05) than in those taking insulin glargine (n=220; -1.3%, 0.06; treatment difference -0.16%, 0.07, 95% CI -0.29 to -0.03). 12 (5%) of 233 patients allocated to exenatide and two (1%) of 223 taking insulin glargine discontinued participation because of adverse events (p=0.012). A planned extension period (up to 2.5 years' duration) is in progress.\n Once weekly exenatide is an important therapeutic option for patients for whom risk of hypoglycaemia, weight loss, and convenience are particular concerns.\n Amylin Pharmaceuticals; Eli Lilly and Company.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "The efficacy and safety of adding liraglutide (a glucagon-like peptide-1 receptor agonist) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes (OAD) therapy.\n In this 26-week, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial, 1,091 subjects were randomly assigned (2:2:2:1:2) to once-daily liraglutide (either 0.6, 1.2, or 1.8 mg/day injected subcutaneously), to placebo, or to glimepiride (4 mg once daily). All treatments were in combination therapy with metformin (1g twice daily). Enrolled subjects (aged 25-79 years) had type 2 diabetes, A1C of 7-11% (previous OAD monotherapy for > or =3 months) or 7-10% (previous OAD combination therapy for > or =3 months), and BMI < or =40 kg/m(2).\n A1C values were significantly reduced in all liraglutide groups versus the placebo group (P < 0.0001) with mean decreases of 1.0% for 1.8 mg liraglutide, 1.2 mg liraglutide, and glimepiride and 0.7% for 0.6 mg liraglutide and an increase of 0.1% for placebo. Body weight decreased in all liraglutide groups (1.8-2.8 kg) compared with an increase in the glimepiride group (1.0 kg; P < 0.0001). The incidence of minor hypoglycemia with liraglutide ( approximately 3%) was comparable to that with placebo but less than that with glimepiride (17%; P < 0.001). Nausea was reported by 11-19% of the liraglutide-treated subjects versus 3-4% in the placebo and glimepiride groups. The incidence of nausea declined over time.\n In subjects with type 2 diabetes, once-daily liraglutide induced similar glycemic control, reduced body weight, and lowered the occurrence of hypoglycemia compared with glimepiride, when both had background therapy of metformin.", "The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride.\n This randomised (using a telephone or web-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA(1c) 7.5-10%) and combination therapy (7.0-10%) was conducted in 107 centres in 17 countries. The primary endpoint was HbA(1c). Patients were randomised (2:1:2) to liraglutide 1.8 mg once daily (n = 232), liraglutide placebo (n = 115) and open-label insulin glargine (n = 234), all in combination with metformin (1 g twice daily) and glimepiride (4 mg once daily). Investigators, participants and study monitors were blinded to the treatment status of the liraglutide and placebo groups at all times.\n The number of patients analysed as intention to treat were: liraglutide n = 230, placebo n = 114, insulin glargine n = 232. Liraglutide reduced HbA(1c) significantly vs glargine (1.33% vs 1.09%; -0.24% difference, 95% CI 0.08, 0.39; p = 0.0015) and placebo (-1.09% difference, 95% CI 0.90, 1.28; p < 0.0001). There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p = 0.0001), and vs glargine (treatment difference -3.43 kg, 95% CI 4.00, 2.86; p < 0.0001). Liraglutide reduced systolic BP (-4.0 mmHg) vs glargine (+0.5 mmHg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine and placebo, respectively). A slightly higher number of adverse events (including nausea at 14%) were reported with liraglutide, but only 9.8% of participants in the group receiving liraglutide developed anti-liraglutide antibodies.\n Liraglutide added to metformin and sulfonylurea produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine. The difference vs insulin glargine in HbA(1c) was within the predefined non-inferiority margin.\n ClinicalTrials.gov NCT00331851.\n The study was funded by Novo Nordisk A/S.", "Unlike most antihyperglycaemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. We compared the efficacy and safety of liraglutide, a human GLP-1 analogue, with exenatide, an exendin-based GLP-1 receptor agonist.\n Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or both, were stratified by previous oral antidiabetic therapy and randomly assigned to receive additional liraglutide 1.8 mg once a day (n=233) or exenatide 10 microg twice a day (n=231) in a 26-week open-label, parallel-group, multinational (15 countries) study. The primary outcome was change in glycosylated haemoglobin (HbA(1c)). Efficacy analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00518882.\n Mean baseline HbA(1c) for the study population was 8.2%. Liraglutide reduced mean HbA(1c) significantly more than did exenatide (-1.12% [SE 0.08] vs -0.79% [0.08]; estimated treatment difference -0.33; 95% CI -0.47 to -0.18; p<0.0001) and more patients achieved a HbA(1c) value of less than 7% (54%vs 43%, respectively; odds ratio 2.02; 95% CI 1.31 to 3.11; p=0.0015). Liraglutide reduced mean fasting plasma glucose more than did exenatide (-1.61 mmol/L [SE 0.20] vs -0.60 mmol/L [0.20]; estimated treatment difference -1.01 mmol/L; 95% CI -1.37 to -0.65; p<0.0001) but postprandial glucose control was less effective after breakfast and dinner. Both drugs promoted similar weight losses (liraglutide -3.24 kg vs exenatide -2.87 kg). Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0.448, p<0.0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1.93 vs 2.60 events per patient per year; rate ratio 0.55; 95% CI 0.34 to 0.88; p=0.0131; 25.5%vs 33.6% had minor hypoglycaemia). Two patients taking both exenatide and a sulphonylurea had a major hypoglycaemic episode.\n Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated. The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations.\n Novo Nordisk A/S.", "Agonists of the glucagon-like peptide-1 (GLP-1) receptor provide pharmacological levels of GLP-1 activity, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors increase concentrations of endogenous GLP-1 and glucose-dependent insulinotropic polypeptide. We aimed to assess the efficacy and safety of the human GLP-1 analogue liraglutide versus the DPP-4 inhibitor sitagliptin, as adjunct treatments to metformin, in individuals with type 2 diabetes who did not achieve adequate glycaemic control with metformin alone.\n In this parallel-group, open-label trial, participants (aged 18-80 years) with type 2 diabetes mellitus who had inadequate glycaemic control (glycosylated haemoglobin [HbA(1c)] 7.5-10.0%) on metformin (>or=1500 mg daily for >or=3 months) were enrolled and treated at office-based sites in Europe, the USA, and Canada. Participants were randomly allocated to receive 26 weeks' treatment with 1.2 mg (n=225) or 1.8 mg (n=221) subcutaneous liraglutide once daily, or 100 mg oral sitagliptin once daily (n=219). The primary endpoint was change in HbA(1c) from baseline to week 26. The efficacy of liraglutide versus sitagliptin was assessed hierarchically by a non-inferiority comparison, with a margin of 0.4%, followed by a superiority comparison. Analyses were done on the full analysis set with missing values imputed by last observation carried forward; seven patients assigned to liraglutide did not receive treatment and thus did not meet criteria for inclusion in the full analysis set. This trial is registered with ClinicalTrials.gov, number NCT00700817.\n Greater lowering of mean HbA(1c) (8.5% at baseline) was achieved with 1.8 mg liraglutide (-1.50%, 95% CI -1.63 to -1.37, n=218) and 1.2 mg liraglutide (-1.24%, -1.37 to -1.11, n=221) than with sitagliptin (-0.90%, -1.03 to -0.77, n=219). Estimated mean treatment differences for liraglutide versus sitagliptin were -0.60% (95% CI -0.77 to -0.43, p<0.0001) for 1.8 mg and -0.34% (-0.51 to -0.16, p<0.0001) for 1.2 mg liraglutide. Nausea was more common with liraglutide (59 [27%] patients on 1.8 mg; 46 [21%] on 1.2 mg) than with sitagliptin (10 [5%]). Minor hypoglycaemia was recorded in about 5% of participants in each treatment group.\n Liraglutide was superior to sitagliptin for reduction of HbA(1c), and was well tolerated with minimum risk of hypoglycaemia. These findings support the use of liraglutide as an effective GLP-1 agent to add to metformin.\n Novo Nordisk.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "To determine the efficacy and safety of liraglutide (a glucagon-like peptide-1 receptor agonist) when added to metformin and rosiglitazone in type 2 diabetes.\n This 26-week, double-blind, placebo-controlled, parallel-group trial randomized 533 subjects (1:1:1) to once-daily liraglutide (1.2 or 1.8 mg) or liraglutide placebo in combination with metformin (1 g twice daily) and rosiglitazone (4 mg twice daily). Subjects had type 2 diabetes, A1C 7-11% (previous oral antidiabetes drug [OAD] monotherapy >or=3 months) or 7-10% (previous OAD combination therapy >or=3 months), and BMI <or=45 kg/m(2).\n Mean A1C values decreased significantly more in the liraglutide groups versus placebo (mean +/- SE -1.5 +/- 0.1% for both 1.2 and 1.8 mg liraglutide and -0.5 +/- 0.1% for placebo). Fasting plasma glucose decreased by 40, 44, and 8 mg/dl for 1.2 and 1.8 mg and placebo, respectively, and 90-min postprandial glucose decreased by 47, 49, and 14 mg/dl, respectively (P < 0.001 for all liraglutide groups vs. placebo). Dose-dependent weight loss occurred with 1.2 and 1.8 mg liraglutide (1.0 +/- 0.3 and 2.0 +/- 0.3 kg, respectively) (P < 0.0001) compared with weight gain with placebo (0.6 +/- 0.3 kg). Systolic blood pressure decreased by 6.7, 5.6, and 1.1 mmHg with 1.2 and 1.8 mg liraglutide and placebo, respectively. Significant increases in C-peptide and homeostasis model assessment of beta-cell function and significant decreases in the proinsulin-to-insulin ratio occurred with liraglutide versus placebo. Minor hypoglycemia occurred more frequently with liraglutide, but there was no major hypoglycemia. Gastrointestinal adverse events were more common with liraglutide, but most occurred early and were transient.\n Liraglutide combined with metformin and a thiazolidinedione is a well-tolerated combination therapy for type 2 diabetes, providing significant improvements in glycemic control.", "The study objective was to investigate the safety and tolerability of up-titration to high doses of taspoglutide, a once-weekly human glucagon-like peptide-1 analogue, in subjects with Type 2 diabetes inadequately controlled on metformin alone.\n In this double-blind phase II trial, subjects were randomized to placebo or taspoglutide (20 mg; three separate groups) administered once weekly by subcutaneous injection for 4 weeks. This was followed by dose maintenance at 20 mg, or titration to 30 mg (20/30) or 40 mg (20/40) once weekly with matched placebo for an additional 4 weeks. Subjects were monitored for adverse events (AEs) throughout the study and 4-week follow-up.\n One hundred and twenty-nine subjects were randomized and treated [mean age 57 years, mean baseline glycated haemoglobin (HbA(1c)), 7.9%]. The most frequently reported AEs were nausea and vomiting. The number of patients reporting gastrointestinal AEs did not increase following titration to higher doses of taspoglutide or when continuing the initial 20 mg regimen. Three subjects were withdrawn from the study as a result of gastrointestinal AEs (one before and two after titration to higher doses). Although not designed to investigate efficacy, improvement in glycaemic control was observed in all active arms of the study. The proportion of subjects achieving HbA(1c) < 7.0% after 8 weeks of treatment was 72, 53 and 70% in the 20/20-, 20/30- and 20/40-mg arms, respectively, vs. 19% for placebo.\n Taspoglutide was safe, well tolerated at high doses and efficacious for lowering HbA(1c). Up-titration of dose was not associated with a worsening AE profile." ]

[ "17973696", "18270586" ]

[ "Effect of training for care providers on practice of essential newborn care in hospitals in Sri Lanka.", "Effect of newborn resuscitation training on health worker practices in Pumwani Hospital, Kenya." ]

[ "To evaluate the effectiveness of a training program for care providers in improving practice of essential newborn care in obstetric units.\n Before-and-after study with an intervention and a control group.\n Five hospitals in the Puttalam district in Sri Lanka.\n Eight hundred and ninety-two mother-newborn pairs (446 before and 446 three months after).\n A 4-day training program on essential newborn care for doctors, nurses, and midwives of the obstetric units in two hospitals.\n By direct observation, practices of essential newborn care at delivery in the labor room on a subsample. By interviewing mothers, immediate skin-to-skin contact and early initiation of breastfeeding. From health records, \"undesirable health events\" of the newborns.\n Practices of cleanliness, thermal protection, and neonatal assessment improved significantly in the intervention group. The intervention was effective in improving skin-to-skin contact by 1.5 times and early initiation of breastfeeding by 3.4 times. Undesirable health events declined from 32 to 21 per 223 newborns in the intervention group and from 20 to 17 per 223 newborns in the control group.\n A comprehensive 4-day training program can be followed by a significant improvement in essential newborn care practices in obstetric units.", "Birth asphyxia kills 0.7 to 1.6 million newborns a year globally with 99% of deaths in developing countries. Effective newborn resuscitation could reduce this burden of disease but the training of health-care providers in low income settings is often outdated. Our aim was to determine if a simple one day newborn resuscitation training (NRT) alters health worker resuscitation practices in a public hospital setting in Kenya.\n We conducted a randomised, controlled trial with health workers receiving early training with NRT (n = 28) or late training (the control group, n = 55). The training was adapted locally from the approach of the UK Resuscitation Council. The primary outcome was the proportion of appropriate initial resuscitation steps with the frequency of inappropriate practices as a secondary outcome. Data were collected on 97 and 115 resuscitation episodes over 7 weeks after early training in the intervention and control groups respectively. Trained providers demonstrated a higher proportion of adequate initial resuscitation steps compared to the control group (trained 66% vs control 27%; risk ratio 2.45, [95% CI 1.75-3.42], p<0.001, adjusted for clustering). In addition, there was a statistically significant reduction in the frequency of inappropriate and potentially harmful practices per resuscitation in the trained group (trained 0.53 vs control 0.92; mean difference 0.40, [95% CI 0.13-0.66], p = 0.004).\n Implementation of a simple, one day newborn resuscitation training can be followed immediately by significant improvement in health workers' practices. However, evidence of the effects on long term performance or clinical outcomes can only be established by larger cluster randomised trials.\n Controlled-Trials.com ISRCTN92218092." ]

[ "4623673" ]

[ "Do Rh-negative women with an early spontaneous abortion need Rh immune prophylaxis?" ]

[ "nan" ]

[ "7969210", "7715792" ]

[ "Pergolide compared with bromocriptine in Parkinson's disease: a multicenter, crossover, controlled study.", "Pergolide in the treatment of Parkinson's disease." ]

[ "We compared the efficacy and safety of pergolide and bromocriptine in 57 patients with Parkinson's disease (PD) with a declining response to levodopa therapy in a single-blind, crossover study. Patients were placed randomly on the sequence bromocriptine-pergolide (12 + 12 weeks) or vice versa. Regular evaluations using the New York University Parkinson's Disease Scale were performed by a clinician blinded to treatment assignment. Patients' and clinicians' impressions also were recorded. The average daily dose of pergolide was 2.3 +/0- 0.8 mg, and that of bromocriptine was 24.2 +/- 8.4 mg. Significantly greater efficacy was demonstrated by both drugs as adjunctive therapy to levodopa compared with previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005; Wilcoxon t test). Pergolide was more effective than bromocriptine in daily living scores (p = 0.020) and motor scores (p = 0.038). No difference in dyskinesias, dystonias, and psychosis was observed. Adverse events were more frequent in bromocriptine-treated patients. Most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short-term trial.", "Three trials evaluated the efficacy and safety of pergolide. Eighty-six de novo patients and 314 patients already receiving levodopa were enrolled in an open-label study. Of the de novo patients, 47.5% showed a marked or moderate improvement and 32% showed a mild improvement. In the levodopa add-on group, 53.8% showed marked or moderate improvement and 36.3% showed mild improvement. In a short-term, double-blind study, the efficacy of pergolide was compared with that of bromocriptine. One hundred seventy-two patients were randomized to receive pergolide, and 173 were randomized to receive bromocriptine. In de novo patients, bromocriptine (n = 49) and pergolide (n = 49) demonstrated similar efficacy. However, significantly more levodopa-treated patients in the pergolide group, compared with the bromocriptine group, demonstrated marked or moderate improvements in several items of the rating scale score. In a long-term study, 151 of 314 patients receiving pergolide in combination with levodopa remained in the study for 3 years, and 127 for 4 years, and in these patients the initial improvement was maintained. In 18 of 62 de novo patients, the initial improvement was maintained for up to 3 years. These trials indicate that pergolide has efficacy in patients with Parkinson's disease, either as monotherapy or in combination with levodopa." ]

[ "9159735", "14663041", "16476934", "11924889", "15304592", "12221159", "12873857", "6236286", "6461156", "1839644", "16434666", "2575450", "9595988", "17030764", "2143808", "8723144", "6241563", "8714171", "9221965", "9222184" ]

[ "A controlled trial of fluoxetine in nondepressed patients with Huntington's disease.", "Dosage effects of riluzole in Huntington's disease: a multicenter placebo-controlled study.", "Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial.", "A randomised, placebo-controlled, double blind study of treatment of Huntington's disease with unsaturated fatty acids.", "Minocycline safety and tolerability in Huntington disease.", "Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine.", "A randomized trial of amantadine in Huntington disease.", "A double blind trial of sulpiride in Huntington's disease and tardive dyskinesia.", "Tiapride in the treatment of Huntington's chorea.", "Controlled clinical trial of cannabidiol in Huntington's disease.", "Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2'dG.", "Effects of terguride in patients with Huntington's disease.", "Safety and tolerability of the free-radical scavenger OPC-14117 in Huntington's disease. The Huntington Study Group.", "Effect of donepezil on motor and cognitive function in Huntington disease.", "L-acetyl-carnitine in Huntington's disease: double-blind placebo controlled crossover study of drug effects on movement disorder and dementia.", "A controlled trial of remacemide hydrochloride in Huntington's disease.", "Tiapride versus placebo: a double-blind comparative study in the management of Huntington's chorea.", "[The effect of piracetam on involuntary movements in Huntington's disease. A double-blind, placebo-controlled study].", "Clozapine versus placebo in Huntington's disease: a double blind randomised comparative study.", "Cognitive, behavioral, and motor effects of the NMDA antagonist ketamine in Huntington's disease." ]

[ "To examine the antidepressant specificity of fluoxetine in Huntington's disease (HD), we carried out a randomized, double-blind, placebo-controlled trial of this medication in nondepressed HD patients. Thirty patients with early HD who were depressed (Hamilton Depression Inventory < 16) were randomized to placebo (N = 13) or fluoxetine 20 mg/day (N = 17) and were followed up for 4 months. Outcome measures included changes in total functional capacity (TFC) and in standardized neurological, cognitive, and behavioral ratings. After adjustment for the higher education level found in the placebo group at baseline, no differences between the treatment groups were found in TFC, neurological, or cognitive ratings. Fluoxetine-treated patients did show a slight reduction in agitation and in the need for routine. Although fluoxetine may be a useful antidepressant in depressed HD patients, it failed to exert substantial clinical benefits in nondepressed HD patients.", "Riluzole retards striatal glutamate release and pathologic consequences in neurotoxic animal models of Huntington's disease (HD).\n To determine the dosage-related impact of riluzole on chorea in HD.\n An 8-week double-blind dose-ranging multicenter study of riluzole was conducted in 63 subjects (32 women, 31 men) with HD who were randomized to receive placebo, riluzole 100 mg/day, or riluzole 200 mg/day. The prespecified outcome measure was change in the total maximal chorea score of the Unified Huntington's Disease Rating Scale (UHDRS).\n Fifty-six (89%) subjects completed the study. A reduction (p < 0.01) in chorea at 8 weeks was found using a linear trend test with dose. Comparing the groups individually, the reduction in chorea for the riluzole 200-mg/day group (-2.2 +/- 3.3) was different (p = 0.01) from placebo (+0.7 +/- 3.4), but the riluzole 100-mg/day group (-0.2 +/- 2.9) was not. Riluzole did not improve other motor, cognitive, behavioral, or functional components of the UHDRS. Alanine aminotransferase was elevated in a dosage-dependent fashion (p = 0.01).\n Over 8 weeks of treatment, riluzole 200 mg/day ameliorated chorea intensity in HD without improving functional capacity or other clinical features of illness. Riluzole 200 mg/day was attended by reversible liver transaminase abnormalities that would require monitoring in long-term studies.", "Tetrabenazine (TBZ) selectively depletes central monoamines by reversibly binding to the type 2 vesicular monoamine transporter. Open-label reports indicate TBZ is effective in treating chorea.\n To examine the safety, efficacy, and dose tolerability of TBZ for treating chorea in Huntington disease (HD).\n The authors randomized 84 ambulatory patients with HD to receive TBZ (n = 54) or placebo (n = 30) for 12 weeks. TBZ was increased over 7 weeks up to a maximum of 100 mg/day or until the desired antichoreic effect occurred or intolerable adverse effects supervened. The primary outcome was the change from baseline in the chorea score of the Unified Huntington's Disease Rating Scale (UHDRS) RESULTS: TBZ treatment resulted in a reduction of 5.0 units in chorea severity compared with a reduction of 1.5 units on placebo treatment (adjusted mean effect size = -3.5 +/- 0.8 UHDRS units [mean +/- SE]; 95% CI: -5.2, -1.9; p < 0.0001). There was also a significant benefit on ratings of clinical global improvement. There were five study withdrawals in the TBZ group and five serious adverse events (SAEs) in four subjects (drowning suicide, complicated fall, restlessness/suicidal ideation, and breast cancer) compared with one withdrawal and no SAEs in the placebo group.\n Tetrabenazine (TBZ), at adjusted dosages of up to 100 mg/day, effectively lessens chorea in ambulatory patients with Huntington disease. TBZ should be dosed individually based on ongoing assessment of possible adverse side effects.", "Huntington's Disease (HD) is a serious dominantly inherited neurodegenerative disorder for which there are no current treatments. Open label and animal studies have suggested that highly unsaturated fatty acids (HUFAs) may be beneficial. Seventeen patients with HD were entered into a randomised, placebo-controlled, double blind trial of HUFA therapy. Patients were assessed on the Rockland-Simpson Dyskinesia Rating Scale (RSDRS) and the Unified Huntington's Disease Rating Scale (UHDRS). On the RSDRS and the UHDRs motor scale patients on HUFA treatment improved while those on placebo deteriorated, with a significant difference between the two groups on the RSDRS. A similar trend was noted on the UHDRS functional performance scales. Little change was seen on the neuropsychology scales. There were no treatment-related adverse events. This is the first time that a significant improvement has been noted in a randomised trial in HD. The results are consistent with open label observations; a second placebo-controlled study in end-stage patients, and a study in a transgenic mouse model of HD.", "Minocycline is an antibiotic with anti-inflammatory and antiapoptotic properties that prolongs survival in a transgenic Huntington disease (HD) mouse model. In a double-blind, randomized, placebo-controlled study of minocycline in 60 HD patients, the authors determined that over 8 weeks, minocycline at 100 and 200 mg/day was well tolerated and safe in HD patients. Tolerability and adverse event frequency were similar between treatment and placebo groups.", "To examine the acute effects of the NMDA receptor antagonist amantadine on motor and cognitive function in Huntington's disease (HD).\n Chorea in HD and in the levodopa-induced dyskinesias of PD may be clinically indistinguishable. In PD, hyperphosphorylation of NMDA receptors expressed on striatal medium spiny neurons contributes to peak-dose dyskinesias, and drugs that block these receptors can diminish chorea severity. Because these spiny neurons are the primary target of the neurodegenerative process in HD, sensitization of NMDA receptors on residual striatal neurons might also participate in the generation of motor dysfunction in HD.\n To evaluate this possibility, 24 patients with HD entered a double-blind placebo-controlled crossover study of amantadine with two 2-week arms.\n Chorea scores were lower with amantadine (usually 400 mg/d) than placebo, with a median reduction in extremity chorea at rest of 36% (p = 0.04) for all 22 evaluable patients and of 56% in the 10 individuals with the highest plasma drug levels. Improvement correlated with plasma amantadine concentrations (p = 0.01) but not CAG repeat length. Parkinsonian rating scores did not worsen and there was no consistent change in cognitive measures. Adverse event profile was benign.\n Results suggest that NMDA receptor supersensitivity may contribute to the clinical expression of choreiform dyskinesias in HD and that selective antagonists at that site can safely confer palliative benefit.", "Huntington chorea, like levodopa-induced dyskinesias, may be responsive to amantadine hydrochloride treatment.\n To measure the effect of amantadine treatment on Huntington chorea and to test a hypothesis that the adventitious movements are associated with reduced central proprioception that can be corrected by amantadine treatment.\n A randomized placebo-controlled cross-over trial with 2 weeks of treatment.\n A tertiary referral center.\n Twenty-four subjects with Huntington disease took amantadine hydrochloride, 100 mg 3 times daily for 2 weeks, and placebo for 2 weeks.\n Chorea of the face, trunk, and limbs while seated was videotaped at baseline and after each study phase. Segments were viewed in random order by blinded reviewers and scored. Proprioception was determined using arm restraints in which the right and left elbows were set at slightly different angles, and the errors in selecting the more extended elbow over 40 trials were recorded.\n The chorea score was not correlated with a proprioception deficit. Neither chorea nor proprioception were significantly affected by amantadine therapy. The chorea score was 9.6 (3.1) points at baseline and 9.7 (3.7) points when the patient was receiving amantadine therapy. The 95% confidence interval for the difference between placebo effect and amantadine effect was -1.43 to 1.0 points. Despite this, 19 subjects felt improved during the amantadine phase compared with 6 subjects improved in the placebo phase (P =.006) and the quality of life was better (P<.001).\n Elbow proprioception was not shown to be related to Huntington chorea. Amantadine hydrochloride treatment at doses of 300 mg/d had no effect, on average, for Huntington chorea, although most patients felt subjectively better during the short course of amantadine treatment.", "Eleven patients with Huntington's disease and nine patients with tardive dyskinesia participated in a randomised double-blind crossover trial of sulpiride (as sole antidopaminergic therapy) versus placebo. Although functional improvement was not seen in Huntington's disease patients, sulpiride reduced movement count and total dyskinesia score in both conditions. Sulpiride differs pharmacologically in several respects from conventional neuroleptics, and has not been convincingly shown to cause tardive dyskinesia. Among currently available treatments, it may therefore be considered a drug of choice for treatment of tardive dyskinesia.", "Twenty-two patients with Huntington's chorea were investigated in a double-blind controlled cross-over trial. The effect was measured by counting the number of involuntary movements from video-recordings and by a Doppler-radar device. Besides these methods, subjective assessments were made on analogue scales by patients, family, nurses and attendant doctors. The quantitative methods revealed no significant diminution of the involuntary movements in the Tiapride therapy period. The subjective evaluation turned out to be useless because of many inconsistent answers.", "Based on encouraging preliminary findings, cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington's Disease (HD). The effects of oral CBD (10 mg/kg/day for 6 weeks) and placebo (sesame oil for 6 weeks) were ascertained weekly under a double-blind, randomized cross-over design. A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables, and on a Cannabis side effect inventory, clinical lab tests and other safety outcome variables, indicated no significant (p greater than 0.05) or clinically important differences. Correspondingly, plasma levels of CBD were assayed by GC/MS, and the weekly levels (mean range of 5.9 to 11.2 ng/ml) did not differ significantly over the 6 weeks of CBD administration. In summary, CBD, at an average daily dose of about 700 mg/day for 6 weeks, was neither symptomatically effective nor toxic, relative to placebo, in neuroleptic-free patients with HD.", "In a randomized, double-blind, placebo-controlled study in 64 subjects with Huntington disease (HD), 8 g/day of creatine administered for 16 weeks was well tolerated and safe. Serum and brain creatine concentrations increased in the creatine-treated group and returned to baseline after washout. Serum 8-hydroxy-2'-deoxyguanosine (8OH2'dG) levels, an indicator of oxidative injury to DNA, were markedly elevated in HD and reduced by creatine treatment.", "trans-Dihydrolisuride, a partial dopamine receptor agonist, was tested for its effects on chorea in a double-blind, crossover clinical study in 10 patients with Huntington's disease. In eight patients, a neurophysiological evaluation was also performed. No reduction in choreic movements or improvement in voluntary movement performance was observed. However, in some patients, there was a slight improvement in patients' alertness and a reduction of the movement reaction time.", "Oxidative damage due to free-radical generation in the setting of underlying defects of neuronal energy metabolism has been implicated as a pathogenetic mechanism for Huntington's disease (HD). The authors conducted a randomized, double-blind, placebo-controlled, multicenter trial of the tolerability of OPC-14117, a lipophilic free-radical scavenger that concentrates in the brain. Ambulatory patients with HD received OPC-14117 60 mg/d, 120 mg/d, 240 mg/d, or placebo and were assessed by the Unified Huntington's Disease Rating Scale (UHDRS) for 20 weeks, including 12 or 16 weeks of assigned treatment and 8 or 4 weeks of blinded withdrawal of the study drug. Tolerability was measured by the proportion of patients completing the initial 12-week course of treatment on their originally assigned regimen. Sixty-four patients were enrolled in the study, 56 of whom completed the 12 weeks of treatment. Treatment was discontinued in four patients (1 placebo, 1 60 mg/d, 2 240 mg/d) due to asymptomatic but persistent serum elevations of liver transaminase. Two patients (1 60 mg/d and 1 120 mg/d) withdrew because of increased involuntary movements, one patient (60 mg/d) withdrew due to persistent dry eyes, and one patient (120 mg/d) withdrew because of persistent vomiting. There were no significant differences between treatment arms in the primary measures of tolerability, the frequency and types of clinical adverse events, or the clinical/functional features of HD. OPC-14117 was safe and generally well tolerated; however, elevations of liver transaminase suggested that continued surveillance monitoring is warranted in conducting more long-term studies of this antioxidant therapy.", "Striatal cholinergic dysfunction may be important in Huntington disease (HD). We studied whether donepezil improves chorea, cognition, and quality of life (QoL) in HD. Thirty patients were randomly assigned to treatment with donepezil or placebo. At the doses studied, donepezil did not improve chorea, cognition, or QoL. Adverse events were similar between both groups. Based on this small sample study, donepezil was not an effective treatment for HD.", "nan", "We conducted a randomized, double-blind, placebo-controlled tolerability study of a N-methyl-D-aspartate (NMDA) glutamate receptor ion-channel blocker, remacemide hydrochloride, in 31 independently ambulatory patients (18 men, 13 women) with Huntington's disease (HD). Subjects were randomized to receive either placebo or active remacemide at dosages of 200 mg/day or 600 mg/day. The primary outcome measure was the proportion of subjects able to complete the study with the assigned treatment. Remacemide was generally well tolerated, and no significant differences between the treatment arms were found in the primary outcome measure. A trend toward improvement in chorea was observed among subjects administered remacemide 200 mg/day. Based on the tolerability and safety demonstrated during this short-term trial, remacemide warrants more extended controlled investigation in patients with HD.", "A double-blind, placebo-controlled, crossover trial was carried out in 29 patients with Huntington's chorea to evaluate the effectiveness and tolerance of high doses of tiapride in the management of neurological symptoms. Patients were allocated at random into 3 groups to receive 3 g tiapride daily for two periods of 3 weeks either preceded, interrupted or followed by a 3-week period on placebo. Patients were assessed on entry and at the end of each treatment period using a battery of tests designed to measure choreatic movements, motor skills, recognition and reaction times, and mental state. Twenty-three patients completed the trial; only 2 of the 6 drop-outs withdrew because of drug-related side-effects (sedation and extrapyramidal signs). The results showed that tiapride treatment significantly improved choreatic movements and motor skills and these findings were supported by the objective psychometric measurements. Overall evaluation of effectiveness by the physician and patients indicated the significant superiority of tiapride over placebo. Treatment was generally well tolerated and although there were significantly more reports of sedation and extrapyramidal signs whilst patients were receiving tiapride, these effects were rated as mild in most cases and did not interfere with treatment.", "Piracetam and its derivatives, a group of \"nootropic\" drugs thought to act as metabolic enhancers in the brain, have been widely used to treat a variety of cognitive disorders. Two studies have reported that this compound reduces the severity of involuntary movements in acute onset hemichorea. We therefore randomly assigned 11 patients with Huntington's disease to receive high doses of intravenous piracetam (12 g in 250 ml of saline) or placebo on different days. A blinded observer then rated the severity of involuntary movements over a period of 4 hours. Significant aggravation (p < 0.05) of chorea was seen in patients taking piracetam, in comparison with ratings for both baseline and placebo, 4 hours after administration but not during earlier assessments. Although the mechanism causing this effect is unidentified, we believe that our findings indicate that piracetam should not be used to treat the cognitive disorders accompanying Huntington's disease.", "To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease.\n Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington's disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. Patients and their partners completed a questionnaire regarding functional disability. Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed separately.\n Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine. Neuroleptic naive patients reported aggravation of functional disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties.\n Clozapine has little beneficial effect in patients with Huntington's disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group.", "Excitotoxicity may contribute to neuronal degeneration in Huntington's disease (HD). N-methyl-D-aspartate (NMDA) receptor antagonists can prevent neuronal degeneration caused by excitotoxicity, but their effects in HD patients are not known.\n We investigated the acute cognitive, behavioral, and motor effects of the NMDA-receptor antagonist ketamine in HD patients. Double-blind infusions of 0.10, 0.40, and 0.60 mg/kg/hr ketamine were given to 10 HD patients on one test day and compared with placebo infusions on a second, identical testing day. Linear mixed-effects models and randomization tests were used to identify whether, and at which dose, a significant change from baseline occurred in outcome variables.\n We demonstrated that ketamine is well tolerated at low and intermediate subanesthetic doses. Intermediate ketamine doses produced specific decline in memory and verbal fluency. Higher subanesthetic doses caused a significant increase in psychiatric symptoms and impairment of eye movements.\n These results describe the spectrum of clinical effects produced by increasing NMDA receptor blockade in HD patients. The clinical effects appearing with higher levels of NMDA receptor blockade can identify the range of doses used in clinical trials of NMDA receptor antagonists." ]

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[ "1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial.", "Prevention of femoral and lumbar bone loss with hormone replacement therapy and vitamin D3 in early postmenopausal women: a population-based 5-year randomized trial.", "Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study.", "A randomized controlled trial of vitamin D3 supplementation in African American women.", "Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial.", "A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS).", "Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial.", "Does vitamin D stop inpatients falling? A randomised controlled trial.", "Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation.", "Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial.", "Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily.", "A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study.", "Randomised controlled trial of prevention of falls in people aged > or =75 with severe visual impairment: the VIP trial.", "Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women.", "Once-weekly dose of 8400 IU vitamin D(3) compared with placebo: effects on neuromuscular function and tolerability in older adults with vitamin D insufficiency.", "Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women.", "The effects of an open design on trial participant recruitment, compliance and retention--a randomized controlled trial comparison with a blinded, placebo-controlled design.", "Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial.", "Amelioration of hemiplegia-associated osteopenia more than 4 years after stroke by 1 alpha-hydroxyvitamin D3 and calcium supplementation.", "Vitamin D supplementation and bone mineral density in early postmenopausal women.", "Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study.", "Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial.", "Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss.", "Does daily vitamin D 800 IU and calcium 1000 mg supplementation decrease the risk of falling in ambulatory women aged 65-71 years? A 3-year randomized population-based trial (OSTPRE-FPS).", "A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study.", "Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial.", "Calcitriol treatment is not effective in postmenopausal osteoporosis.", "Skeletal site-dependent response of bone mineral density and quantitative ultrasound parameters following a 12-month dietary intervention using dairy products fortified with calcium and vitamin D: the Postmenopausal Health Study.", "Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older.", "Calcium- and vitamin D3-fortified milk reduces bone loss at clinically relevant skeletal sites in older men: a 2-year randomized controlled trial.", "Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients.", "Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial.", "Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care.", "Calcium and vitamin D supplementation increases spinal BMD in healthy, postmenopausal women.", "Clinical and laboratory safety of one year's use of a combination calcium + vitamin D tablet in ambulatory elderly women with vitamin D insufficiency: results of a multicenter, randomized, double-blind, placebo-controlled study.", "Vitamin D3 and calcium to prevent hip fractures in the elderly women.", "Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation.", "Effect of supplementation with vitamin D3 and calcium on quantitative ultrasound of bone in elderly institutionalized women: a longitudinal study.", "Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents.", "Effects of calcium and vitamin D supplementation on hip bone mineral density and calcium-related analytes in elderly ambulatory Australian women: a five-year randomized controlled trial.", "Effect of ipriflavone on bone in elderly hemiplegic stroke patients with hypovitaminosis D.", "Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial.", "Amelioration of osteopenia and hypovitaminosis D by 1alpha-hydroxyvitamin D3 in elderly patients with Parkinson's disease.", "Calcium plus vitamin D supplementation and the risk of fractures.", "The effects of vitamin D supplementation on physical function and quality of life in older patients with heart failure: a randomized controlled trial.", "Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial.", "Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial.", "Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial.", "Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial.", "Do vitamin D supplements improve the physical capabilities of elderly hospital patients?" ]

[ "An unexplained loss of muscle strength occurs with aging. Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [1,25-(OH2)D3] to persons with low serum concentrations can improve strength. To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [1,25-(OH2)D3], we conducted a randomized, controlled, double blinded trial in 98 men and women volunteers over 69 yr old. Treatment consisted of 0.25 micrograms 1,25-(OH)2D3, orally, twice per day or identical placebo for 6 months. Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer. There was no difference between the two groups at 1 week, 1 month, or 6 months of treatment in any of the measures of muscle strength. We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons. Further research is needed to determine the etiology of the decline in muscle strength associated with aging.", "The long term effects of hormone replacement therapy (HRT) and vitamin D3 (Vit D) on bone mineral density (BMD) were studied. A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study (n = 13100) were randomized to four groups: 1) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate, 2) Vit D3 (300 and 100 IU/day during the fifth year), 3) HRT and Vit D combined, and 4) placebo. Lumbar (L2-L4) and femoral neck BMD were determined by dual x-ray absorptiometry (DXA) at baseline and after 2.5 and 5 yr of treatment. Intention to treat analysis (n = 464) showed that after 5 yr, lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [+0.2% (P = 0.658) and +0.9% (P = 0.117), respectively], whereas lumbar BMD decreased by 4.6% in the Vit D group and by 4.5% in the placebo group (P < 0.001 in both). The loss of femoral neck BMD was less in the HRT (-1.4%; P = 0.005) and HRT plus Vit D (-1.3%; P = 0.003) groups than in the Vit D and placebo groups (-4.3%; P < 0.001 in both). Among those 370 women who complied with the 5-yr treatment, the effect was more pronounced: lumbar BMD had increased by 1.5% in the HRT (P = 0.009) and by 1.8% in the HRT plus Vit D group (P = 0.005), with a plateau after 2.5 yr, whereas lumbar BMD had decreased in both the Vit D and placebo groups (4.6% and 4.7%; P < 0.001, respectively). Femoral neck BMD decreased again less in the HRT (-0.4%) and HRT plus Vit D (-0.6%) groups than in the Vit D and placebo groups (-4.4% in both). This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis. The data suggest that low dose vitamin D3 supplementation does not prevent bone loss in healthy, nonosteoporotic, early postmenopausal women, and it confers no benefit additional to that of HRT alone.", "Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people. Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures, as proved by Decalyos I. Decalyos II is a 2-year, multicenter, randomized, double-masked, placebo-controlled confirmatory study. The intention-to-treat population consisted of 583 ambulatory institutionalized women (mean age 85.2 years, SD = 7.1) randomized to the calcium-vitamin D3 fixed combination group (n = 199); the calcium plus vitamin D3 separate combination group (n = 190) and the placebo group (n = 194). Fixed and separate combination groups received the same daily amount of calcium (1200 mg) and vitamin D3 (800 IU), which had similar pharmacodynamic effects. Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent, with levels returning within the normal range after 6 months. In a subgroup of 114 patients, femoral neck bone mineral density (BMD) decreased in the placebo group (mean = -2.36% per year, SD = 4.92), while remaining unchanged in women treated with calcium-vitamin D3 (mean = 0.29% per year, SD = 8.63). The difference between the two groups was 2.65% (95% CI = -0.44, 5.75%) with a trend in favor of the active treatment group. No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis. The relative risk (RR) of HF in the placebo group compared with the active treatment group was 1.69 (95% CI = 0.96, 3.0), which is similar to that found in Decalyos I (RR = 1.7; 95% CI = 1.0, 2.8). Thus, these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women.", "We conducted a randomized, placebo-controlled, double-blind trial to test the hypothesis that vitamin D(3) supplementation would prevent bone loss in calcium-replete, African American postmenopausal women.\n Two hundred eight healthy black postmenopausal women, 50 to 75 years of age, were assigned to receive either placebo or 20 microg/d (800 IU) of vitamin D(3). Calcium supplements were provided to ensure a total calcium intake of 1200 to 1500 mg/d. After 2 years, the vitamin D(3) dose was increased to 50 microg/d (2000 IU) in the active group, and the study continued for an additional year. Bone mineral density (BMD) was measured every 6 months. Markers of bone turnover, vitamin D metabolites, and parathyroid hormone (PTH) levels were measured in serum.\n There were no significant differences in BMD between the active and control groups throughout the study. There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss. There was an increase in BMD of the total body, hip, and radius at 1 year in both groups. Over the 3 years, BMD declined at these sites by 0.26% to 0.55% per year. The BMD of the lumbar spine increased slightly in the placebo and active groups. There were no persistent changes in serum PTH levels or the markers of bone turnover, although there was a transient decline in PTH in both groups at 3 months. No significant adverse events were attributed to vitamin D supplementation.\n There was no observed effect of vitamin D(3) supplementation on bone loss or bone turnover markers in calcium-replete, postmenopausal African American women. Further studies are needed to determine if these findings are applicable to women of other ethnic groups.", "Bone metabolism follows a seasonal pattern with high bone turnover and bone loss during the winter. In a randomized, open-label 2-year sequential follow-up study of 55 healthy adults, we found that supplementation with oral vitamin D3 and calcium during winter abolished seasonal changes in calciotropic hormones and markers of bone turnover and led to an increase in BMD. Supplementation with oral vitamin D3 and calcium during the winter months seems to counteract the effects of seasonal changes in vitamin D and thus may be beneficial as a primary prevention strategy for age-related bone loss.\n Bone metabolism follows a seasonal pattern characterized by high bone turnover and bone loss during winter. We investigated whether wintertime supplementation with oral vitamin D3 and calcium had beneficial effects on the circannual changes in bone turnover and bone mass.\n This prospective study comprised an initial observation period of 12 months (\"year 1\"), followed by an intervention during parts of year 2. Fifty-five healthy subjects living in southwestern Germany (latitude, 49.5 degrees N) were randomized into two groups: 30 subjects were assigned to the treatment group and received oral cholecalciferol (500 IU/day) and calcium (500 mg/day) during the winter months of year 2 (October-April), while 25 subjects assigned to the control group obtained no supplements. Primary endpoints were changes in calciotropic hormones [serum 25(OH)D, 1,25(OH)2D, and parathyroid hormone], markers of bone formation (serum bone-specific alkaline phosphatase) and of bone resorption (urinary pyridinoline and deoxypyridinoline), and changes in lumbar spine and femoral neck BMD.\n Forty-three subjects completed the study. During year 1, calciotropic hormones, markers of bone turnover, and BMD varied by season in both groups. During the winter months of year 1, bone turnover was significantly accelerated, and lumbar spine and femoral BMD declined by 0.3-0.9%. In year 2, seasonal changes in calciotropic hormones and markers of bone turnover were either reversed or abolished in the intervention group while unchanged in the control cohort. In the subjects receiving oral vitamin D3 and calcium, lumbar and femoral BMD increased significantly (lumbar spine: +0.8%, p = 0.04 versus year 1; femoral neck: +0.1%, p = 0.05 versus year 1), whereas controls continued to lose bone (intervention group versus control group: lumbar spine, p = 0.03; femoral neck, p = 0.05).\n Supplementation with oral vitamin D3 and calcium during winter prevents seasonal changes in bone turnover and bone loss in healthy adults. It seems conceivable that annually recurring cycles of low vitamin D and mild secondary hyperparathyroidism during the winter months contributes, at least in part and over many years, to age-related bone loss. Supplementation with low-dose oral vitamin D3 and calcium during winter may be an efficient and inexpensive strategy for the primary prevention of bone loss in northern latitudes.", "To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge.\n Multicenter, randomized, controlled trial with a factorial design.\n Five hospitals in Auckland, New Zealand, and Sydney, Australia.\n Two hundred forty-three frail older people.\n Patients were randomized to receive a single dose of vitamin D (calciferol, 300,000 IU) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits.\n The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months. Physical performance and self-rated function were secondary endpoints. Assessments took place in the participants' homes at 3 and 6 months after randomization and were performed by blinded assessors.\n There was no effect of either intervention on physical health or falls, but patients in the exercise group were at increased risk of musculoskeletal injury (risk ratio = 3.6, 95% confidence interval = 1.5-8.0). Vitamin D supplementation did not improve physical performance, even in those who were vitamin D deficient (<12 ng/mL) at baseline.\n Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization. There was no effect of vitamin D on physical performance, and the exercises increased the risk of musculoskeletal injury. These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people.", "To determine whether vitamin D supplementation decreases the incidence of hip fractures and other peripheral bone fractures.\n Prospective, double-blind trial.\n Community setting (Amsterdam and surrounding area).\n 2578 persons (1916 women, 662 men) 70 years of age and older (mean age +/- SD, 80 +/- 6 years) living independently, in apartments for elderly persons, or in homes for elderly persons.\n Participants were randomly assigned to receive either vitamin D3, 400 IU in one tablet daily, or placebo for a maximum of 3.5 years.\n Dietary calcium intake and serum 25-hydroxyvitamin D [25(OH)D] were estimated in a subset of participants. During follow-up, attention was concentrated on hip fractures and other peripheral fractures. The maximal follow-up period was 4 years. The results were evaluated by survival analysis.\n Mean dietary calcium intake from dairy products was 868 mg/d. Mean serum 25(OH)D concentration in the third year of the study was 23 nmol/L in the placebo group and 60 nmol/L in the vitamin D group. Median follow-up was 3.5 years, and total follow-up was 8450 patient-years. During follow-up, 306 persons in the placebo group and 282 persons in the vitamin D group died (P = 0.20). Hip fractures occurred in 48 persons in the placebo group and 58 persons in the vitamin D group (P = 0.39, intention-to-treat analysis). Other peripheral fractures occurred in 74 persons in the placebo group and 77 persons in the vitamin D group (P = 0.86).\n Our results do not show a decrease in the incidence of hip fractures and other peripheral fractures in Dutch elderly persons after vitamin D supplementation.", "Vitamin D deficiency is common in older people and may increase risk of falls and fracture. Hospital inpatients are at particular risk of falling. Previous studies suggest that vitamin D improves neuromuscular function and reduces falls.\n To determine whether routine supplementation with vitamin D plus calcium reduces numbers of fallers and falls in a cohort of hospital admissions while they are inpatients.\n Randomised, double-blind, controlled study. Participants: two hundred and five acute admissions >65 years to a geriatric medical unit.\n Patients were randomised to intervention of daily vitamin D 800 iu plus calcium 1,200 mg or control group of daily calcium 1,200 mg, until discharge or death.\n Baseline characteristics were similar in both groups with a median age 84 years and a median length of stay = 30 days (IQR 14.75-71.00). In a pre-selected sub-group (54/205 participants), median admission vitamin D level = 22.00 nmol/l (IQR 15.00-30.50). This did not significantly increase in the treatment versus control group. Median study drug adherence = 88%, with no significant difference between study groups (Mann-Whitney: P = 0.711). Although there were fewer fallers in the vitamin D cohort, this did not reach statistical significance (vitamin D: calcium = 36:45 fallers; RR 0.82 (CI 0.59-1.16). Neither the mean number of falls (vitamin D: calcium = 1.040:1.155; Mann-Whitney P = 0.435) or time to first fall (Log-rank test P = 0.377) differed between groups.\n In a population of geriatric hospital inpatients, vitamin D did not reduce the number of fallers. Routine supplementation cannot be recommended to reduce falls in this group.", "Osteoporotic fractures in older people are a major and increasing public health problem. We examined the effect of vitamin D supplementation on fracture rate in people living in sheltered accommodation.\n In a pragmatic double blind randomised controlled trial of 3 years duration, we examined 3,440 people (2,624 women and 816 men) living in residential or care home. We used four-monthly oral supplementation using 100,000 IU vitamin D(2) (ergocalciferol). As a main outcome measure, we used the incidence of first fracture using an intention to treat analysis. This was a multicentre study in 314 care homes or sheltered accommodation complexes in South Wales, UK.\n The vitamin D and placebo groups had similar baseline characteristics. In intention-to-treat analysis, 205 first fractures occurred in the intervention group during a total of 2,846 person years of follow-up (7 fractures per 100 people per year of follow-up), with 218 first fractures in the control group over 2,860 person years of follow-up. The hazard ratio of 0.95 (95% confidence interval 0.79-1.15) for intervention compared to control was not statistically significant.\n Supplementation with four-monthly 100,000 IU of oral vitamin D(2) is not sufficient to affect fracture incidence among older people living in institutional care.", "Elevated circulating concentrations of proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure (CHF). In vitro studies suggest that vitamin D suppresses proinflammatory cytokines and increases antiinflammatory cytokines.\n We evaluated the effect of vitamin D supplementation on the survival rate and different biochemical variables in patients with CHF.\n One hundred twenty-three patients randomly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d [D(+) group] or placebo plus 500 mg Ca/d [D(-) group] for 9 mo. Biochemical variables were assessed at baseline and after 9 mo. The survival rate was calculated for a follow-up period of 15 mo.\n Ninety-three patients completed the study. Significant treatment effects were observed on logarithmic-transformed serum concentrations of 25-hydroxyvitamin D (P = 0.001), parathyroid hormone (P = 0.007), tumor necrosis factor alpha (P = 0.006), and interleukin 10 (P = 0.042). 25-Hydroxyvitamin D increased by 26.8 ng/mL in the D(+) group but increased only by 3.6 ng/mL in the D(-) group. Compared with baseline, parathyroid hormone was significantly lower and the antiinflammatory cytokine interleukin 10 was significantly higher in the D(+) group after 9 mo. The proinflammatory cytokine tumor necrosis factor alpha increased in the D(-) group but remained constant in the D(+) group. The survival rate did not differ significantly between the study groups during the follow-up period.\n Vitamin D(3) reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease. Our data provide evidence for the involvement of an impaired vitamin D-parathyroid hormone axis in the progression of CHF.", "To study the effect of alfacalcidol (1alpha(OH)D3) on fall risk in community-dwelling elderly men and women.\n Randomized, double-blind, placebo-controlled intervention trial.\n Basel, Switzerland.\n Three hundred seventy-eight community-dwelling elderly (191 women/187 men).\n Participants were randomly assigned to receive 1 microg of alfacalcidol or matched placebo daily for 36 weeks.\n Serum 25-hydoxyvitamin D3 (25(OH) D,1,25-dihydroxyvitamin D3 (D-hormone), and intact parathormone (iPTH) levels were measured using radioimmunoassay at baseline and every 12 weeks. Numbers of fallers and falls were assessed using a questionnaire during each study site visit. Dietary calcium intake was assessed at baseline using a food frequency questionnaire.\n At baseline, participants had, on average, normal vitamin D and D-hormone serum levels. Over 36 weeks, alfacalcidol treatment was associated with fewer fallers (odds ratio (OR)=0.69, 95% confidence interval (CI)=0.41-1.16) than placebo. In a post hoc subgroups analysis by medians of total calcium intake, this reduction reached significance in alfacalcidol-treated subjects with a total calcium intake of more than 512 mg/d (OR=0.45, 95% CI=0.21-0.97, P=.042) but not in those who consumed less than 512 mg/d (OR=1.00, 95% CI= 0.47-2.11, P=.998). Alfacalcidol treatment was also, independent of total calcium intake, associated with a significant 37.9% reduction in iPTH serum levels (P<.0001). No cases of clinically relevant hypercalcemia were observed.\n Provided a minimal calcium intake of more than 512 mg/d, alfacalcidol treatment significantly and safely reduces number of fallers in an elderly community dwelling population.", "To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents.\n Secondary data analysis of a previously conducted randomized clinical trial.\n Seven hundred twenty-five-bed long-term care facility.\n One hundred twenty-four nursing home residents (average age 89).\n Participants were randomly assigned to receive one of four vitamin D supplement doses (200 IU, 400 IU, 600 IU, or 800 IU) or placebo daily for 5 months.\n Number of fallers and number of falls assessed using facility incident tracking database.\n Over the 5-month study period, the proportion of participants with falls was 44% in the placebo group (11/25), 58% (15/26) in the 200 IU group, 60% (15/25) in the 400 IU group, 60% (15/25) in the 600 IU group, and 20% (5/23) in the 800 IU group. Participants in the 800 IU group had a 72% lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months (rate ratio=0.28; 95% confidence interval=0.11-0.75). No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups.\n Nursing home residents in the highest vitamin D group (800 IU) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses. Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group.", "To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision.\n Randomised controlled trial.\n Dunedin and Auckland, New Zealand.\n 391 women and men aged > or =75 with visual acuity of 6/24 or worse who were living in the community; 92% (361 of 391) completed one year of follow-up.\n Participants received a home safety assessment and modification programme delivered by an occupational therapist (n = 100), an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation (n = 97), both interventions (n = 98), or social visits (n = 96).\n Numbers of falls and injuries resulting from falls, costs of implementing the home safety programme.\n Fewer falls occurred in the group randomised to the home safety programme but not in the exercise programme (incidence rate ratios 0.59 (95% confidence interval 0.42 to 0.83) and 1.15 (0.82 to 1.61), respectively). However, within the exercise programme, stricter adherence was associated with fewer falls (P = 0.001). A conservative analysis showed neither intervention was effective in reducing injuries from falls. Delivering the home safety programme cost NZ650 dollars (234 pounds sterling, 344 euros, US432 dollars) (at 2004 prices) per fall prevented.\n The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision. The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group, possibly due to low levels of adherence. Trial registration number ISRCTN15342873.", "Ergocalciferol (vitamin D(2)) supplementation plays a role in fall prevention, but the effect in patients living in the community in sunny climates remains uncertain. We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling.\n A 1-year population-based, double-blind, randomized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth, Australia (latitude, 32 degrees S), with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year. Participants were randomized to receive ergocalciferol, 1000 IU/d, or identical placebo (hereinafter, ergocalciferol and control groups, respectively). Both groups received calcium citrate, 1000 mg/d. Fall data were collected every 6 weeks.\n Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height, which was significantly different between the 2 groups (ergocalciferol group, 53.0%; control group, 62.9%; odds ratio [OR], 0.61; 95% confidence interval [CI], 0.37-0.99). When those who fell were grouped by the season of first fall or the number of falls they had, ergocalciferol treatment reduced the risk of having the first fall in winter and spring (ergocalciferol group, 25.2%; control group, 35.8%; OR, 0.55; 95% CI, 0.32-0.96) but not in summer and autumn, and reduced the risk of having 1 fall (ergocalciferol group, 21.2%; control group, 33.8%; OR, 0.50; 95% CI, 0.28-0.88) but not multiple falls.\n Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium, which is associated with a 19% reduction in the relative risk of falling, mostly in winter.", "Vitamin D insufficiency, which is prevalent in older individuals, is associated with bone and muscle weakness and falls.\n We examined the effects of a weekly dose of 8400 IU vitamin D(3) on postural stability, muscle strength, and safety.\n In this double-blind trial, subjects aged > or =70 y with serum 25-hydroxyvitamin D [25(OH)D] concentrations < or =20 but > or =6 ng/mL were randomly assigned to receive a weekly dose of 8400 IU vitamin D(3) (n = 114) or a placebo (n = 112). Mediolateral body sway with eyes open (assessed with the AccuSway(PLUS) platform; Advanced Medical Technology Inc, Watertown, MA) was the primary endpoint. Secondary endpoints included the short physical performance battery (SPPB) and serum 25(OH)D concentrations. An analysis of covariance model was used for treatment comparisons. Safety and tolerability were monitored.\n Serum 25(OH)D concentrations rose significantly (from 13.9 to 26.2 ng/mL, P < 0.001) in patients treated with 8400 IU vitamin D(3) but not in patients treated with the placebo. After 16 wk, neither mediolateral sway nor SPPB differed significantly between treatment groups. However, in the post hoc analysis of patients subgrouped by baseline sway (> or = 0.46 compared with <0.46 cm), treatment with 8400 IU vitamin D(3) significantly reduced sway compared with treatment with placebo (P = 0.047) in patients with elevated baseline sway but not in patients with normal baseline sway. Adverse experiences and incidences of hypercalcemia, hypercalciuria, and elevated creatinine were similar with both treatments. In patients treated with 8400 IU vitamin D(3), but not in placebo-treated patients, parathyroid hormone decreased significantly.\n Weekly treatment with 8400 IU vitamin D(3) raised 25(OH)D concentrations in elderly, vitamin D-insufficient individuals. Treatment with 8400 IU vitamin D(3) did not reduce mediolateral sway significantly compared with treatment with placebo in this population, although in post hoc analysis, treatment with 8400 IU vitamin D(3) reduced sway in the subgroup of patients who had elevated sway at baseline. Weekly treatment with 8400 IU vitamin D(3) was well tolerated. This trial was registered at clinicaltrials.gov as NCT00242476.", "Dietary supplementation with vitamin K(1), with vitamin D(3) and calcium or their combination, was examined in healthy older women during a 2-year, double-blind, placebo-controlled trial. Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius.\n The putative beneficial role of high dietary vitamin K(1) (phylloquinone) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind, placebo-controlled trial in healthy Scottish women > or =60 years of age.\n Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 microg/day vitamin K(1), (3) 10 microg (400 IU) vitamin D(3) plus 1000 mg calcium/day, or (4) combined vitamins K(1) and D(3) plus calcium. Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist, markers of bone turnover, and vitamin status. Supplementation effects were tested using multivariate general linear modeling, with full adjustment for baseline and potential confounding variables.\n Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius. Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years, serum vitamin K(1) increased by 157% (p < 0.001), the percentage of undercarboxylated osteocalcin (%GluOC) decreased by 51% (p < 0.001), serum 25-hydroxyvitamin D [25(OH)D] increased by 17% (p < 0.001), and PTH decreased by 11% (p = 0.049).\n These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1) together with supplements of calcium plus moderate vitamin D(3) to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation.", "In randomized trials there may be no overriding reason whether or not to have a placebo control.\n We assessed the effects of an open trial design (no placebo and people know what tablets they are given) compared with a blinded, placebo-controlled design on recruitment, compliance and retention within a randomized trial of secondary osteoporotic fracture prevention.\n We undertook a randomized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture, recruited in a UK teaching hospital. Randomization was 2:1 in favour of the blinded, placebo-controlled trial design.\n From 180 eligible participants randomized to receive information based on the open trial design, 134 (74.4%) consented to take part, compared with 233 (65.1%) of 358 people randomized to the blinded, placebo-controlled design (difference 9.4%, 95% confidence interval 1.3-17.4%). Reluctance to take a placebo and the desire to know tablet allocation were reasons given for not taking part in the blinded, placebo-controlled design. There was no significant difference in tablet compliance. Open trial participants were more likely to remain in the trial for one year (difference 13.9%, 95% confidence interval 3.1-24.6%), mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group (difference 23.6%, 95% confidence interval 11.9-35.2%). The odds ratio for reporting an adverse event in the open trial compared to the blinded, placebo-controlled design was 0.64 (95% confidence interval 0.28-1.49), and for reporting a fracture was 0.81 (0.36-1.85).\n We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power, but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial.", "Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures.\n In a factorial-design trial, 5292 people aged 70 years or older (4481 [85%] of whom were women) who were mobile before developing a low-trauma fracture were randomly assigned 800 IU daily oral vitamin D3, 1000 mg calcium, oral vitamin D3 (800 IU per day) combined with calcium (1000 mg per day), or placebo. Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months. Analysis was by intention-to-treat and the primary outcome was new low-energy fractures.\n 698 (13%) of 5292 participants had a new low-trauma fracture, 183 (26%) of which were of the hip. The incidence of new, low-trauma fractures did not differ significantly between participants allocated calcium and those who were not (331 [12.6%] of 2617 vs 367 [13.7%] of 2675; hazard ratio (HR) 0.94 [95% CI 0.81-1.09]); between participants allocated vitamin D3 and those who were not (353 [13.3%] of 2649 vs 345 [13.1%] of 2643; 1.02 [0.88-1.19]); or between those allocated combination treatment and those assigned placebo (165 [12.6%] of 1306 vs 179 [13.4%] of 1332; HR for interaction term 1.01 [0.75-1.36]). The groups did not differ in the incidence of all-new fractures, fractures confirmed by radiography, hip fractures, death, number of falls, or quality of life. By 24 months, 2886 (54.5%) of 5292 were still taking tablets, 451 (8.5%) had died, 58 (1.1%) had withdrawn, and 1897 (35.8%) had stopped taking tablets but were still providing data for at least the main outcomes. Compliance with tablets containing calcium was significantly lower (difference: 9.4% [95% CI 6.6-12.2]), partly because of gastrointestinal symptoms. However, potentially serious adverse events were rare and did not differ between groups.\n The findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people.", "It has been demonstrated that bone mass was significantly reduced on the hemiplegic side of stroke patients, which might increase their risk of hip fracture. We evaluated the efficacy of 1 alpha-hydroxyvitamin D3 [1 alpha (OH)D3] and supplemental elemental calcium in maintaining bone mass and decreasing the incidence of hip fractures after hemiplegic stroke.\n In a randomized study, 64 patients with hemiplegia after stroke with a mean duration of illness of 4.8 years received either 1 microgram 1 alpha (OH)D3 daily (treatment group, n = 30) or an inactive placebo (placebo group, n = 34) for 6 months and were observed for this duration. Both groups received 300 mg of elemental calcium daily. The bone mineral density (BMD) and metacarpal index (MCI) in the second metacarpals were determined by computed x-ray densitometry. The incidence of hip fractures in these patients was recorded.\n BMD on the hemiplegic side decreased by 2.4% in the treatment group and 8.9% in the placebo group (P = .0021), while BMD on the intact side increased by 3.5% and decreased by 6.3% in the treated and placebo groups, respectively (P = .0177). In the treatment group, the difference in BMD between hemiplegic and nonhemiplegic sides decreased significantly compared with that before randomization. This difference increased in the placebo group. We observed a similar improvement in MCI in the treatment group but not in the placebo group. Four patients in the placebo group suffered a hip fracture compared with none in the treatment group (P = .0362).\n Treatment with 1 alpha (OH)D3 and supplemental elemental calcium can reduce the risk of hip fractures and can prevent further decreases in BMD and MCI on the hemiplegic side of patients with a long-standing stroke. Treatment also may improve these indices on the intact side.", "Increased vitamin D intake may preserve or increase bone mineral density (BMD) in older persons.\n A 2-y double-blind study was undertaken to determine whether weekly administration of 10 000 units of vitamin D(2) maintained or increased BMD in younger postmenopausal women more efficiently than did calcium supplements alone.\n One hundred eighty-seven women who were >or= 1 y postmenopausal were randomly assigned to take either 1000 mg Ca/d after the evening meal or 1000 mg Ca/d plus 10 000 U vitamin D(2)/wk in a double-blind, placebo-controlled format. The BMD of the proximal forearm, lumbar spine, femoral neck, Ward's triangle, and femoral trochanter was measured at 6-mo intervals by osteodensitometry.\n During the 2-y period, there was no significant difference in the change in BMD at any site between the subjects taking calcium supplements and those taking calcium plus vitamin D(2). Both groups significantly (P < 0.005) gained BMD in Ward's triangle and the femoral trochanter but significantly (P < 0.005) lost bone in the proximal radius. There was no significant change in the lumbar spine or femoral neck BMD.\n In younger postmenopausal women ( age: 56 y) whose average baseline serum 25-hydroxyvitamin D concentration was well within the normal range, the addition of 10 000 U vitamin D(2)/wk to calcium supplementation at 1000 mg/d did not confer benefits on BMD beyond those achieved with calcium supplementation alone.", "This study of 9605 community-dwelling residents supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in elderly in a northern European region known to be deficient in vitamin D, especially during winter periods.\n We evaluated the effect of two programs for the prevention of osteoporotic fractures leading to acute hospital admission in a population of elderly community-dwelling residents.\n This was a factorial, cluster-randomized, pragmatic, intervention study. We included 9605 community-dwelling residents aged 66+ years. We offered a prevention program of a daily supplement of 1000 mg of elemental calcium as calcium carbonate and 400 IU (10 microg) of vitamin D3 to a total of 4957 participants. Another program with evaluation and suggestions for the improvement of the domestic environment was offered to a total of 5063 participants. Both programs included revision of the resident's current pharmaceutical treatment. We achieved information on osteoporotic fractures in the study population from the Danish Hospital Registration Database. We defined osteoporotic fractures as low energy fractures of the proximal humerus, distal forearm, vertebral column, pelvis, cervical femur, and intertrochanteric femur.\n Active participation was 50.3% in the Calcium and Vitamin D Program and 46.4% in the Environmental and Health Program. We observed a 16% reduction in fracture incidence rate (relative risk [RR], 0.84; CI, 0.72-0.98; p < 0.025) among male and female residents offered the Calcium and Vitamin D Program (intention-to-prevent analysis).\n This study supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in community-dwelling elderly people in a northern European region known to be deficient in vitamin D, especially during winter periods.", "Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects. The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-standing stroke by vitamin D supplementation.\n Ninety-six elderly women with poststroke hemiplegia were followed for two years. Patients were randomly assigned to one of the two groups, and 48 patients received 1,000 IU ergocalciferol daily, and the remaining 48 received placebo. The number of falls per person and incidence of hip fractures were compared between the two groups. Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study.\n At baseline, serum 25-hydroxyvitamin D levels were in the deficient range (<10 ng/ml) in all patients; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels. Vitamin D treatment accounted for a 59% reduction in falls (95% CI, 28-81%; p = 0.003). There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group. Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period (log-rank, p = 0.049).\n Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers, which may lead to decreased falls and hip fractures.\n Copyright (c) 2005 S. Karger AG, Basel.", "Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol, are important factors in the pathogenesis of age-related bone loss. The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on bone loss in elderly women. Four hundred eighty-nine elderly women with normal bone density for their age, aged 65-77 yr, were entered into a randomized double blind, placebo-controlled trial. Women were randomized to one of four groups: conjugated estrogens (0.625 mg, daily) to women without a uterus (estrogen replacement therapy) plus medroxyprogesterone acetate (2.5 mg, daily) to women with a uterus (hormone replacement therapy), calcitriol (0.25 microg twice daily), a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol, or placebos for 3 yr. The primary outcome was the change in bone mineral density of the femoral neck and spine. In the intent to treat analysis, hormone therapy (hormone replacement therapy/estrogen replacement therapy) produced a mean (+/-1 SD) increase in bone mineral density of 2.98% (+/-5.45%) at the femoral neck (P < 0.0001) and 4.36% (+/-6.42%) at the spine (P < 0.0001). There were parallel increases in total hip and trochanter bone mineral density. Calcitriol increased bone mineral density 0.10% (+/- 4.27%) at the femoral neck (P = 0.57) and 1.65% (+/- 4.83%) at the spine (P < 0.0124). The combination of hormone replacement therapy/estrogen replacement therapy + calcitriol increased bone mineral density 3.80% (+/-4.95%) at the femoral neck (P < 0.001), 4.91% (+/-6.0%) at the spine (P < 0.0001), and parallel changes at the total hip and trochanter. All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck, spine, total hip and trochanter. There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis. In a secondary analysis of the effect in women who were adherent to treatment, calcitriol had a more significant effect on spine (P = 0.003) and total hip (P = 0.004). The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups. Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter (P = 0.007) and total hip bone mineral density (P = 0.0017). In summary, hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinically relevant sites in a group of elderly women, with normal bone density for their age. Calcitriol was effective in increasing spine bone mineral density. In the adherent women, combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone.", "The hypothesis was that the calcium and vitamin D supplementation prevents falls at the population level.Study design: The OSTPRE-FPS was a randomized population-based open-trial with 3-year follow-up. The supplementation group (n=1566) received daily cholecalciferol 800IU+calcium carbonate 1000mg, while the control group (n=1573) received no supplementation or placebo. A randomly selected subsample of 593 subjects underwent a detailed measurement program including serum 25(OH)D measurements.\n The occurrence of falls was the primary outcome of the study. The participants in the subsample were telephoned at 4 months intervals and the rest of the trial population was interviewed by phone once a year.\n In the entire trial population (ETP), there were 812 women with 1832 falls in the intervention group and 833 women with 1944 falls in the control group (risk ratio was 0.98, 95% CI 0.92-1.05, P=0.160). The supplementation was not associated with single or multiple falls in the ETP. However, in the subsample, multiple fall incidence decreased by 30% (odds ratio (OR) 0.70, 95% CI 0.50-0.97, P=0.034) in the supplementation group. Further, the supplementation decreased the incidence of multiple falls requiring medical attention (OR 0.72, 95% CI 0.53-0.97, P=0.031) in the ETP. The mean compliance in the entire trial population was 78% and in the subsample 79%.\n Overall, the primary analysis showed no association between calcium and vitamin D supplementation and risk of falls. However, the results of a post hoc analysis suggested that there was a decreased risk of multiple falls requiring medical attention: this finding requires confirmation.\n Copyright 2009 Elsevier Ireland Ltd. All rights reserved.", "survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture. There is little consensus about secondary prevention. Many are given calcium and vitamin D, but the evidence supporting this is circumstantial.\n to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers, bone mineral density and rate of falls in elderly women post-hip fracture.\n randomised controlled trial.\n orthogeriatric rehabilitation ward.\n 150 previously independent elderly women, recruited following surgery for hip fracture, were assigned to receive a single injection of 300,000 units of vitamin D(2), injected vitamin D(2) plus 1 g/day oral calcium, 800 units/day oral vitamin D(3) plus 1 g/day calcium, or no treatment. Follow-up was one year, with measurement of 25-hydroxyvitamin D, parathyroid hormone, bone mineral density, and falls.\n mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups, more so in the group receiving combined oral vitamin D and calcium. Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later. Bone mineral density showed small but statistically significant differences of up to 4.6% between actively treated groups and placebo. Relative risk of falling in the groups supplemented with vitamin D was 0.48 (95% CI 0.26-0.90) compared with controls.\n Vitamin D supplementation, either orally or with injected vitamin D, suppresses parathyroid hormone, increases bone mineral density and reduces falls. Effects may be more marked with calcium co-supplementation. The 300,000 units of injected vitamin D may not last a whole year.", "To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient.\n Randomized, placebo-controlled double-blind, trial of 2 years' duration.\n Multicenter study in 60 hostels (assisted living facilities) and 89 nursing homes across Australia.\n Six hundred twenty-five residents (mean age 83.4) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L.\n Vitamin D supplementation (ergocalciferol, initially 10,000 IU given once weekly and then 1,000 IU daily) or placebo for 2 years. All subjects received 600 mg of elemental calcium daily as calcium carbonate.\n Falls and fractures recorded prospectively in study diaries by care staff.\n The vitamin D and placebo groups had similar baseline characteristics. In intention-to-treat analysis, the incident rate ratio for falling was 0.73 (95% confidence interval (CI)=0.57-0.95). The odds ratio for ever falling was 0.82 (95% CI=0.59-1.12) and for ever fracturing was 0.69 (95% CI=0.40-1.18). An a priori subgroup analysis of subjects who took at least half the prescribed capsules (n=540), demonstrated an incident rate ratio for falls of 0.63 (95% CI=0.48-0.82), an odds ratio (OR) for ever falling of 0.70 (95% CI=0.50-0.99), and an OR for ever fracturing of 0.68 (95% CI=0.38-1.22).\n Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient.", "To determine if calcitriol is an effective treatment in postmenopausal osteoporosis.\n Double-blind, randomized clinical trial of 2 years' duration.\n University medical center with patients recruited by media announcements.\n Eighty-six postmenopausal women with vertebral compression fractures.\n Patients were treated with calcitriol or placebo. Mean dose was 0.43 micrograms/d. Dietary calcium was 1000 mg/d (24.9 mmol/d). The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia.\n No significant differences between placebo and control groups were seen in the percent change in total body calcium (0.4% +/- 1.0 compared with 0.0% +/- 0.9), single photon absorptiometry (-0.5% +/- 1.2 compared with -3.1% +/- 0.9) or dual photon absorptiometry (0.0% +/- 1.7 compared with -1.0% +/- 2.2). New fractures were seen in 16% of the placebo group and 26% of the calcitriol groups, so the difference in percent fractures was 10% (95% CI, -5.7% to 25.7%). Bone biopsies did not show changes in either group. The calcitriol group had significantly higher serum and urine calcium values, but renal function was not worse than in the placebo group.\n Calcitriol is not an effective treatment for established postmenopausal osteoporosis.", "The aim of the current study was to examine whether calcium supplementation could prevent bone loss in postmenopausal women or more favourable outcomes could be obtained via the consumption of dairy products fortified with calcium and vitamin D3. For this purpose changes in bone mineral density (BMD) at different skeletal sites, assessed by dual-energy X-ray absorptiometry, as well as in quantitative ultrasound (QUS) parameters of the calcaneus over 12 months were estimated. A population of 101 postmenopausal women (55-65 years old) was randomized into a dairy group (DG: n 39), receiving approximately 1200 mg calcium/d and 7.5 microg vitamin D3/d through fortified dairy products; a calcium-supplemented group (CaG: n 26) provided with a calcium supplement of 600 mg/d; and a control group (CG: n 36). Over the intervention period the DG was found to have more favourable changes in pelvis (P=0.040), total spine (P<0.001) and total body BMD (P<0.001) than the other groups. A significant increase was also observed for DG in lumbar spine BMD (2.0%; 95% CI 0.5, 3.5) although it did not differentiate significantly compared to the other groups. No significant differences were observed with respect to the changes in QUS parameters. The current study revealed that recommended intakes of vitamin D3 and calcium via fortified dairy products for 12 months can induce favourable changes in pelvis, total spine and total body BMD in postmenopausal women but not in QUS parameters. No such favourable changes were observed via supplementation of calcium alone.", "Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons.\n We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density, biochemical measures of bone metabolism, and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home. They received either 500 mg of calcium plus 700 IU of vitamin D3 (cholecalciferol) per day or placebo. Bone mineral density was measured by dual-energy x-ray absorptiometry, blood and urine were analyzed every six months, and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records.\n The mean (+/-SD) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows: femoral neck, +0.50+/-4.80 and -0.70+/-5.03 percent, respectively (P=0.02); spine,+2.12+/-4.06 and +1.22+/-4.25 percent (P=0.04); and total body, +0.06+/-1.83 and -1.09+/-1.71 percent (P<0.001). The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year, but it was significant only for total-body bone mineral density in the second and third years. Of 37 subjects who had nonvertebral fractures, 26 were in the placebo group and 11 were in the calcium-vitamin D group (P=0.02).\n In men and women 65 years of age or older who are living in the community, dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck, spine, and total body over the three-year study period and reduced the incidence of nonvertebral fractures.", "In this 2-year randomized controlled study of 167 men >50 years of age, supplementation with calcium-vitamin D3-fortified milk providing an additional 1000 mg of calcium and 800 IU of vitamin D3 per day was effective for suppressing PTH and stopping or slowing bone loss at several clinically important skeletal sites at risk for fracture.\n Low dietary calcium and inadequate vitamin D stores have long been implicated in age-related bone loss and osteoporosis. The aim of this study was to assess the effects of calcium and vitamin D3 fortified milk on BMD in community living men >50 years of age.\n This was a 2-year randomized controlled study in which 167 men (mean age +/- SD, 61.9 +/- 7.7 years) were assigned to receive either 400 ml/day of reduced fat ( approximately 1%) ultra-high temperature (UHT) milk containing 1000 mg of calcium plus 800 IU of vitamin D3 or to a control group receiving no additional milk. Primary endpoints were changes in BMD, serum 25(OH)D, and PTH.\n One hundred forty-nine men completed the study. Baseline characteristics between the groups were not different; mean dietary calcium and serum 25(OH)D levels were 941 +/- 387 mg/day and 77 +/- 23 nM, respectively. After 2 years, the mean percent change in BMD was 0.9-1.6% less in the milk supplementation compared with control group at the femoral neck, total hip, and ultradistal radius (range, p < 0.08 to p < 0.001 after adjusting for covariates). There was a greater increase in lumbar spine BMD in the milk supplementation group after 12 and 18 months (0.8-1.0%, p < or = 0.05), but the between-group difference was not significant after 2 years (0.7%; 95% CI, -0.3, 1.7). Serum 25(OH)D increased and PTH decreased in the milk supplementation relative to control group after the first year (31% and -18%, respectively; both p < 0.001), and these differences remained after 2 years. Body weight remained unchanged in both groups at the completion of the study.\n Supplementing the diet of men >50 years of age with reduced-fat calcium- and vitamin D3-enriched milk may represent a simple, nutritionally sound and cost-effective strategy to reduce age-related bone loss at several skeletal sites at risk for fracture in the elderly.", "to evaluate the effects of vitamin D supplementation on parathyroid function and bone turnover in aged, chronically immobile patients.\n a randomised double-blind controlled trial.\n two hundred and eighteen long-term inpatients aged over 65 years.\n the patients were randomised into treatment groups of I-III, each receiving 0 IU, 400 IU and 1200 IU cholecalciferol per day, respectively. In case of inadequate consumption of dairy products, patients received a daily calcium substitution of 500 mg.\n plasma concentrations of 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (PTH), amino-terminal propeptide of type I procollagen (PINP), a marker of bone formation, and carboxy-terminal telopeptide of type I collagen (ICTP), a marker of bone resorption, were measured at baseline and after 6 months.\n the patients (age 84.5 years) were chronically bedridden. The baseline 25-OHD was low (23 nmol/l), correlated inversely with PINP, and tended to associate inversely with PTH. The prevalence of vitamin D deficiency (VDD) (25-OHD < 50 nmol/l) was 98% and PTH was elevated in 23% of the patients. Vitamin D supplementation significantly increased 25-OHD concentrations (124% group II, 204% group III) and decreased PTH (-7% group II, -8% group III). PINP tended to decrease, but ICTP tended to increase, and only their ratio decreased significantly. The tendency of ICTP to increase was inconsistent. Changes in 25-OHD correlated inversely with those in PTH and PINP.\n vitamin D supplementation has minor effects on PTH and bone turnover in chronically immobilised aged patients with VDD. Further comparative studies and meta-analyses are warranted to elucidate the confounding effects of different mobility levels on the benefits of vitamin D supplementation in patients with differing baseline PTH levels.", "To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community.\n Randomised double blind controlled trial of 100 000 IU oral vitamin D3 (cholecalciferol) supplementation or matching placebo every four months over five years.\n 2686 people (2037 men and 649 women) aged 65-85 years living in the general community, recruited from the British doctors register and a general practice register in Suffolk.\n Fracture incidence and total mortality by cause.\n After five years 268 men and women had incident fractures, of whom 147 had fractures in common osteoporotic sites (hip, wrist or forearm, or vertebrae). Relative risks in the vitamin D group compared with the placebo group were 0.78 (95% confidence interval 0.61 to 0.99, P=0.04) for any first fracture and 0.67 (0.48 to 0.93, P=0.02) for first hip, wrist or forearm, or vertebral fracture. 471 participants died. The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 (0.74 to 1.06, P=0.18). Findings were consistent in men and women and in doctors and the general practice population.\n Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community.", "To assess whether supplementation with calcium and cholecaliferol (vitamin D3) reduces the risk of fracture in women with one or more risk factors for fracture of the hip.\n Pragmatic open randomised controlled trial.\n Practice nurse led clinics in primary care.\n 3314 women aged 70 and over with one or more risk factors for hip fracture: any previous fracture, low body weight (< 58 kg), smoker, family history of hip fracture, or fair or poor self reported health.\n Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls, or leaflet only (control group).\n Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment, falls, and quality of life (measured with the SF-12).\n 69% of the women who completed the follow-up questionnaire at 24 months were still taking supplements (55% with inclusion of randomised participants known to be alive). After a median follow-up of 25 months (range 18 to 42 months), clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures (odds ratio for fracture in supplemented group 1.01, 95% confidence interval 0.71 to 1.43). The odds ratio for hip fracture was 0.75 (0.31 to 1.78). The odds of a woman having a fall at six and 12 months was 0.99 and 0.98, respectively. Quality of life did not significantly differ between the groups.\n We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture. Registration ISRCTN26118436, controlled trials registry.", "We undertook a double-masked, randomized, placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement and a calcium supplement plus multivitamins on bone loss at the hip, spine and forearm. The study was performed in 240 healthy women, 58-67 years of age. Duration of treatment was 2 years. Bone mineral density (BMD) was measured at the lumbar spine, hip and forearm. A dietary questionnaire was administered twice during the study and revealed a fairly good calcium and vitamin D intake (919 mg calcium/day; 3.8 micrograms vitamin D/day). An increase in lumbar spine BMD of 1.6% was observed in the treatment group after 2 years (p < 0.002). In the placebo group no significant changes were observed during the 2 years. Lumbar spine BMD was significantly higher in the treatment group at both 1 (p < 0.01) and 2 years (p < 0.05) compared with the placebo group. Though not significant, the same trend was seen at the hip. No significant changes from baseline values were observed at the distal forearm in either the treatment or the placebo group. In conclusion, we found a significant increase in urinary calcium excretion in the treatment group compared with the placebo group. Together with significant changes in serum calcium and serum parathyroid hormone, this indicates that a long-term calcium and vitamin supplement of 1 g elementary calcium (calcium carbonate) and 14 micrograms vitamin D3 increases intestinal calcium absorption. A positive effect on BMD was demonstrated, even in a group of early postmenopausal age, with a fairly good initial calcium and vitamin D status.", "This article presents the results of an evaluation of the clinical and laboratory safety of a 1-year course of treatment with a combination calcium and vitamin D tablet in ambulatory women aged >65 years with vitamin D insufficiency.\n In a multicenter, randomized, double-blind, placebo-controlled study conducted in France, women with a 25-hydroxyvitamin D level < or =12 ng/mL were randomized to receive either a combination tablet containing calcium carbonate 500 mg and vitamin D3 400 IU taken twice daily or a matching placebo tablet for 1 year. A complete clinical examination was performed at baseline and at 3, 6, 9, and 12 months of treatment; blood and urine samples were collected for laboratory analyses at the same time points. Safety was monitored based on adverse events recorded during the treatment period and on the results of laboratory tests, including measurement of creatinine and uric acid levels.\n The study included 192 women (mean [SD] age, 74.6 [6.9] years; mean weight, 64.0 [12.5] kg), 95 in the calcium + vitamin D group and 97 in the placebo group. Fifty women (21/95 [22.1%] calcium + vitamin D, 29/96 [30.2%] placebo) were prematurely withdrawn from the study for various reasons, with no difference in withdrawals between groups. Treatment-related adverse events were reported in 21 (22.1%) and 23 (24.0%) women in the respective treatment groups. These events consisted mainly of metabolic disorders (9 [9.5%] and 10 [10.4%], respectively), particularly hypercalcemia (6 [6.3%] and 8 [8.3%]) and gastrointestinal disorders (9 [9.5%] and 8 [8.3%]). No major complications directly related to calcium and vitamin D supplementation occurred during the course of treatment. Although renal function was not altered, the group who received calcium + vitamin D had significantly elevated concentrations of serum uric acid compared with those who received placebo (52.3% vs 37.2%; P = 0.046) but not urinary uric acid.\n In these ambulatory elderly women with vitamin D deficiency, supplementation with calcium + vitamin D appeared to be well tolerated over 1 year of treatment. No significant effects on creatinine clearance were observed. However, the proportion of women with elevated serum uric acid concentrations was significantly greater in those who received calcium + vitamin D compared with those who received placebo.", "Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known.\n We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women.\n Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001).\n Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.", "To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation.\n A randomised controlled trial of cluster design.\n 223 Residential units (mainly identical 30-bedded units), within 118 homes for elderly people throughout Britain, with 3,717 participating residents (76% women, average age 85 years). The units provided mainly or entirely residential care (35% of residents), nursing care (42%) or care for elderly mentally infirm (EMI) residents (23%).\n Participants were randomly allocated by residential unit (cluster design) to a treated group offered ergocalciferol 2.5 mg every 3 months (equivalent to a daily dose of 1,100 IU), or to a control group. Fractures were reported by staff and confirmed in hospital, and routinely collected data on reported falls were obtained.\n After median follow-up of 10 months (interquartile range 7-14 months), 64 (3.6%) of 1,762 vitamin D-treated residents and 51 (2.6%) of 1,955 controls had one or more non-vertebral fractures, and 24 (1.3%) and 20 (1.0%), respectively, had a hip fracture. The proportion reporting at least one fall was 44% in vitamin D-treated and 43% in control residents. The differences between the vitamin D and control groups were not statistically significant. The incidence of all non-vertebral fractures in the care homes (3.2% per year) and of hip fractures (1.1% per year) was low, similar to rates in elderly people in sheltered accommodation, and the pre-treatment serum 25-hydroxy vitamin D concentration was high [median 47 nmol/l, measured in a 1% (n = 18) sample].\n We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation.", "Supplementation of elderly institutionalized women with vitamin D and calcium decreased hip fractures and increased hip bone mineral density. Quantitative ultrasound (QUS) measurements can be performed in nursing homes, and easily repeated for follow-up. However, the effect of the correction of vitamin D deficiency on QUS parameters is not known. Therefore, 248 institutionalized women aged 62-98 years were included in a 2-year open controlled study. They were randomized into a treated group (n = 124), receiving 440 IU of vitamin D3 combined with 500 mg calcium (1250 mg calcium carbonate, Novartis) twice daily, and a control group (n = 124). One hundred and three women (42%), aged 84.5 +/- 7.5 years, completed the study: 50 in the treated group, 53 in the controls. QUS of the calcaneus, which measures BUA (broadband ultrasound attenuation) and SOS (speed of sound), and biochemical analysis were performed before and after 1 and 2 years of treatment. Only the results of the women with a complete follow-up were taken into account. Both groups had low initial mean serum 25-hydroxyvitamin D levels (11.9 +/- 1.2 and 11.7 +/- 1.2 micrograms/l; normal range 6.4-40.2 micrograms/l) and normal mean serum parathyroid hormone (PTH) levels (43.1 +/- 3.2 and 44.6 +/- 3.5 ng/l; normal range 10-70 ng/l, normal mean 31.8 +/- 2.3 ng/l). The treatment led to a correction of the metabolic disturbances, with an increase in 25-hydroxyvitamin D by 123% (p < 0.01) and a decrease in PTH by 18% (p < 0.05) and of alkaline phosphatase by 15% (p < 0.01). In the controls there was a worsening of the hypovitaminosis D, with a decrease of 25-hydroxyvitamin D by 51% (p < 0.01) and an increase in PTH by 51% (p < 0.01), while the serum calcium level decreased by only 2% (p < 0.01). After 2 years of treatment BUA increased significantly by 1.6% in the treated group (p < 0.05), and decreased by 2.3% in the controls (p < 0.01). Therefore, the difference in BUA between the treated subjects and the controls (3.9%) was significant after 2 years (p < 0.01). However, SOS decreased by the same amount in both groups (approximately 0.5%). In conclusion, BUA, but not SOS, reflected the positive effect on bone of supplementation with calcium and vitamin D3 in a population of elderly institutionalized women.", "The effect of equivalent oral doses of vitamin D3 600 IU/day, 4200 IU/week and 18,000 IU/month on vitamin D status was compared in a randomized clinical trial in nursing home residents. A daily dose was more effective than a weekly dose, and a monthly dose was the least effective.\n It is assumed that equivalent daily, weekly or monthly doses of vitamin D3 equally influence vitamin D status. This was investigated in a randomized clinical trial in nursing home residents.\n The study was performed in ten nursing homes including 338 subjects (76 male and 262 female), with a mean age of 84 (+/- SD 6.3 years). They received oral vitamin D3 either 600 IU/day, or 4200 IU/week, or 18,000 IU/month or placebo. After 4 months, calcium was added during 2 weeks, 320 mg/day or 640 mg/day or placebo. Outcome: serum levels of 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and bone turnover markers. Statistical approach: linear multilevel analysis.\n At baseline, mean serum 25(OH)D was 25.0 nmol/L (SD 10.9), and in 98%, it was lower than 50 nmol/L. After 4 months, mean serum 25(OH)D levels increased to 62.5 nmol/L (after daily vitamin D3 69.9 nmol/L, weekly 67.2 nmol/L and monthly 53.1 nmol/L, P < 0.001 between groups). Median serum PTH levels decreased by 23% (p < 0.001). Bone turnover markers did not decrease. Calcium supplementation had no effect on serum PTH and bone turnover.\n Daily vitamin D was more effective than weekly, and monthly administration was the least effective.", "Effects of long-term calcium, with or without vitamin D, on hip bone mineral density (BMD) and bone turnover in sunny climates have not been reported.\n The aim was to evaluate the effect of vitamin D added to calcium supplementation on hip dual-energy x-ray absorptiometry BMD and calcium-related analytes.\n The study was a 5-yr randomized, controlled, double-blind trial of 120 community-dwelling women aged 70-80 yr.\n The interventions were 1200 mg/d calcium with placebo vitamin D (Ca group) or with 1000 IU/d vitamin D2 (CaD group), or double placebo (control).\n Hip BMD, plasma 25-hydroxyvitamin D, biomarkers of bone turnover, PTH, and intestinal calcium absorption were measured.\n Hip BMD was preserved in CaD (-0.17%) and Ca (0.19%) groups but not controls (-1.27%) at yr 1 and maintained in the CaD group only at yr 3 and 5. The beneficial effects were mainly in those with baseline 25-hydroxyvitamin D levels below the median (68 nmol/liter). At yr 1, compared with controls, the Ca and CaD groups had 6.8 and 11.3% lower plasma alkaline phosphatase, respectively (P<or=0.02), and 28.7 and 34.5% lower urinary deoxypyridinoline to creatinine ratio, respectively (P<or=0.05). At 5 yr, this suppression was maintained only in the CaD group. CaD reduced PTH at 3 and 5 yr cf. controls (27.8 and 31.3%, P<or=0.005) in those with baseline PTH levels above the median (3.6 pmol/liter). Therapy did not affect intestinal calcium absorption at high carrier loads.\n Addition of vitamin D to calcium has long-term beneficial effects on bone density in elderly women living in a sunny climate, probably mediated by a long-term reduction in bone turnover rate.", "A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side, correlating with the degree of paralysis and vitamin D deficiency due to malnutrition, sunlight deprivation, and immobilization-induced hypercalcemia, and increases the risk of hip fracture. We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [1alpha(OH)D3; vitamin D3] administration on bone mineral density preservation as compared with untreated controls. In a randomized and prospective study of 103 patients with hemiplegia after stroke (the mean duration of illness was 4.8 yr), 68 (34 patients in each group) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo, whereas the remaining 35 patients received no drug. Bone mineral density on the hemiplegic side decreased by 1.4% in the ipriflavone group, 3.8% in the vitamin D3 group, and 5.4% in the control group (P < .0001, ipriflavone v vitamin D3 and control). At baseline, all three groups of patients showed a 25-hydroxyvitamin D insufficiency, increased serum ionized calcium, and low levels of 1, 25-dihydroxyvitamin D, suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1, 25-dihydroxyvitamin D. After treatment, the serum 1, 25-dihydroxyvitamin D level increased by 139.9% in the ipriflavone group and by 26.9% in the vitamin D3 group. Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group, whereas no changes occurred in the other two groups. One patient in the untreated group suffered a hip fracture, compared with none in the ipriflavone and vitamin D3 groups. These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1, 25-dihydroxyvitamin D concentration.", "The purpose of the study was to determine the effect of vitamin D supplementation on bone turnover and bone loss in elderly women. Three hundred forty-eight women, ages 70 yr and older, were randomized to receive 400 IU vitamin D3 per day (n = 177) or placebo (n = 171), double-blind, for a period of 2 yr. Main outcome measures were bone mineral density of both hips (femoral neck and trochanter) and the distal radius, as well as biochemical markers of bone turnover. The effect of vitamin D supplementation was expressed as the difference in mean (percentage) change between the placebo group and the vitamin D group. The measurements were repeated in 283 women after 1 yr and in 248 women after 2 yr. Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D (250HD) (+35 nmol/L) and 1,25-dehydroxyvitamin D [1,25-(OH)2D] (+7.0 pmol/L) levels and urinary calcium/creatinine ratios (+0.5%) and significantly decreased PTH(1-84) secretion (-0.74 pmol/L) after 1 yr. No effect was found for the parameters of bone turnover. The effect on the bone mineral density of the left femoral neck was +1.8% in the first yr, +0.2% in the second yr, and +1.9% during the whole period (95% confidence interval 0.4, 3.4%). At the right femoral neck the effects were +1.5%, +1.1%, and +2.6% (confidence interval 1.1, 4.0%), respectively. No effect was found at the femoral trochanter and the distal radius. Supplementation with 400 IU vitamin D3 daily in elderly women slightly decreases PTH secretion and increases bone mineral density at the femoral neck.", "A high prevalence of hip and other fractures in elderly patients with Parkinson's disease has been linked to reduced bone mass arising from a defect of renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D). Treatment with 1alpha-hydroxyvitamin D3 (1alpha(OH)D3; an active form of vitamin D) was evaluated for maintaining bone mass and reducing the incidence of hip and other nonvertebral fractures in patients with Parkinson's disease.\n In a double blind, randomised trial, 86 elderly patients with Parkinson's disease (mean Hoehn and Yahr stage, 3; mean age 70.6 years) were randomised to receive either 1 microg 1alpha(OH)D3 daily (treatment group, n=43) or a placebo (n=43) for 18 months. Bone mineral densities in the second metacarpals were determined by computed radiographic densitometry. Serum bone turnover indices were measured serially, and incidence of nonvertebral fractures was recorded.\n Bone mineral densities decreased 1.2% in the treatment group compared with 6.7% in the placebo group during 18 months (p<0.0001). At baseline in both groups, the serum concentration of 1, 25-[OH]2D was reduced. Parathyroid hormone was abnormally increased in 15 patients (17%) and correlated negatively with serum 25-hydroxyvitamin D, indicating compensatory hyperparathyroidism. Eight patients sustained fractures (six at the hip and two at other sites) in the placebo group, and one hip fracture occurred among treated patients (odds ratio 9.8; p=0.0028).\n By increasing serum 1, 25-[OH]2D concentrations, treatment with 1alpha(OH)D3 can reduce the risk of hip and other non-vertebral fractures in osteoporotic elderly patients with Parkinson's disease by slowing the loss of bone mineral densities.", "The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal.\n We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers.\n Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels.\n Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).\n Copyright 2006 Massachusetts Medical Society", "Low 25-hydroxyvitamin D levels, commonly found in older patients with heart failure, may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance. We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life.\n In a randomized, parallel group, double-blind, placebo-controlled trial, patients with systolic heart failure aged >or=70 years with 25-hydroxyvitamin D levels <50 nmol/L (20 ng/mL) received 100,000 U of oral vitamin D2 or placebo at baseline and 10 weeks. Outcomes measured at baseline, 10 weeks, and 20 weeks were 6-minute walk distance, quality of life (Minnesota score), daily activity measured by accelerometry, Functional Limitations Profile, B-type natriuretic peptide, and tumor necrosis factor-alpha. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks (22.9 versus 2.3 nmol/L [9.2 versus 0.9 ng/mL]; P<0.001) and maintained this increase at 20 weeks. The 6-minute walk did not improve in the treatment group relative to placebo. No significant benefit was seen on timed up and go testing, subjective measures of function, daily activity, or tumor necrosis factor. Quality of life worsened by a small, but significant amount in the treatment group relative to placebo. B-type natriuretic peptide decreased in the treatment group relative to placebo (-22 versus +78 pg/mL at 10 weeks; P=0.04).\n Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency. Clinical Trial Registration- www.controlled-trials.com. Identifier: ISRCTN51372896.", "Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers. However, interventional studies to test this effect are lacking.\n The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types.\n This was a 4-y, population-based, double-blind, randomized placebo-controlled trial. The primary outcome was fracture incidence, and the principal secondary outcome was cancer incidence. The subjects were 1179 community-dwelling women randomly selected from the population of healthy postmenopausal women aged >55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were randomly assigned to receive 1400-1500 mg supplemental calcium/d alone (Ca-only), supplemental calcium plus 1100 IU vitamin D3/d (Ca + D), or placebo.\n When analyzed by intention to treat, cancer incidence was lower in the Ca + D women than in the placebo control subjects (P < 0.03). With the use of logistic regression, the unadjusted relative risks (RR) of incident cancer in the Ca + D and Ca-only groups were 0.402 (P = 0.01) and 0.532 (P = 0.06), respectively. When analysis was confined to cancers diagnosed after the first 12 mo, RR for the Ca + D group fell to 0.232 (CI: 0.09, 0.60; P < 0.005) but did not change significantly for the Ca-only group. In multiple logistic regression models, both treatment and serum 25-hydroxyvitamin D concentrations were significant, independent predictors of cancer risk.\n Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00352170.", "Low trauma fractures in older people incur enormous physical, social and economic costs. Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group. This strategy requires validation in a population setting.\n Randomized, double-blind, placebo-controlled trial of 300,000 IU intramuscular (i.m.) vitamin D2 (ergocalciferol) injection or matching placebo every autumn over 3 years. 9440 people (4354 men and 5086 women) aged 75 yrs and over were recruited from general practice registers in Wessex, England. Primary outcome measure was all non-vertebral fracture. Secondary outcomes were hip and wrist fractures, and all falls.\n 585 subjects had incident non-spine fractures (hip 110, wrist 116, ankle 37). Hazard ratios (HRs) for fracture in the vitamin D group were: 1.09 [95% confidence interval (CI) 0.93-1.28, P = 0.29] for any first fracture, 1.49 (95% CI 1.02-2.18, P = 0.04) for hip and 1.22 (95% CI 0.85-1.76, P = 0.28) for wrist. There was no effect on falls: HR 0.98 (0.93-1.04). No protective effect was observed in any subgroup when the cohort was stratified by sex, age, previous fracture or mobility.\n An annual i.m. injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population.", "Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.\n To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.\n A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.\n 500,000 IU of cholecalciferol or placebo.\n Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.\n Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.\n Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.\n anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867.", "Specific receptors for vitamin D have been identified in human muscle tissue. Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double-blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63-99 years) in long-stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D-group; n = 62) or 1200 mg calcium (Cal-group; n = 60) per day over a 12-week treatment period. The number of falls per person (0, 1, 2-5, 6-7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6-week pretreatment period, and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment - pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed up&go test) was measured as a secondary outcome. Among subjects in the Cal+D-group, there were significant increases in median serum 25-hydroxyvitamin D (+71%) and 1,25-dihydroxyvitamin D (+8%). Before treatment, mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group. In the 12-week treatment period, mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group. After adjustment, Cal+D-treatment accounted for a 49% reduction of falls (95% CI, 14-71%; p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal-group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D-group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.", "A randomized double-blind controlled trial of the effect of vitamin D supplementation on the abilities of elderly hospital patients to carry out basic activities of daily life is described. Those patients included in the trial had plasma 25-hydroxyvitamin D concentrations which were low or low normal as judged by the normal range in young adults. After 2 to 9 months on the trial there was no significant difference in the performance of the control and treatment groups." ]

[ "1918555", "16618688", "9638782", "8664135" ]

[ "Preparing patients for cancer chemotherapy: effect of coping preparation and relaxation interventions.", "Effects of an education program on radiation oncology patients and families.", "Reducing distress in cancer patients with an orientation program.", "A randomised trial of two information packages distributed to new cancer patients before their initial appointment at a regional cancer centre." ]

[ "Sixty cancer chemotherapy patients were randomly assigned to one of four treatments: (a) relaxation training with guided relaxation imagery (RT), (b) general coping preparation package (PREP), (c) both RT and PREP, or (d) routine clinic treatment only. All patients were assessed on self-report, nurse observation, family observation, and physiological measures and were followed for five sequential chemotherapy treatments. Results indicate that the PREP intervention increased patients' knowledge of the disease and its treatment, reduced anticipatory side effects, reduced negative affect, and improved general coping. RT patients showed some decrease in negative affect and vomiting, but not as great as in past studies. The data suggest that a relatively simple, one-session coping preparation intervention can reduce many different types of distress associated with cancer chemotherapy and may be more effective than often-used behavioral relaxation procedures.", "Patients and family members in a radiation oncology department participated in a study of a new education/orientation program. Information was presented in oral and in written form. After the intervention, orientation program participants did not differ significantly from control group members in state anxiety, general distress, treatment adherence, or knowledge of radiation therapy. Orientation group patients reported greater satisfaction with clinic care, and the orientation group was significantly more likely to utilize psychological counseling services within the clinic, as well as outside support. Discussion focused on possible explanations for the strikingly favorable program evaluations given by participants despite little evidence that the program was of significant benefit.", "The purpose of this study was to test a brief orientation program for reducing anxiety, depressive symptoms, and overall distress in cancer patients at their initial clinic visit. One hundred and fifty consecutively referred patients seen in an oncology outpatient clinic were randomly assigned to an intervention or usual care control group. The intervention group received a clinic tour, general information about clinic operations, and a question and answer session with an oncology counselor. Outcome measures included the State-Trait Anxiety Inventory (STAI), the Brief Profile of Mood States (POMS), the Center for Epidemiologic Studies-Depression (CES-D) Scale, and an oncology clinic questionnaire which were administered at the initial clinic visit and follow-up. There were no statistically significant clinical or demographic differences between groups at initial assessment. At follow-up, the intervention group had lower state anxiety, lower overall distress, and fewer patients reporting depressive symptoms. Patients in the intervention group demonstrated significantly more knowledge about clinic operations and greater satisfaction with care. These data provide evidence that anxiety, distress and depressive symptoms can be reduced with an orientation program. This finding has particular relevance in the early stages of diagnosis where patients may suffer symptoms of anxiety and depression.", "The purpose of this study was to evaluate the extent to which a new patient information package (NPIP) or a mini version of the same package (mini-NPIP) reduces emotional distress and meets the informational needs of patients arriving at a tertiary cancer centre for the first time. A comprehensive package, NPIP, consisting of procedural information regarding cancer centre location, description of the health care team, treatment services, research, educational activities, accommodation and community services provided at the centre; and a condensed version of the same package, mini-NPIP, were developed. Consecutive patients with newly diagnosed breast, gynaecological, lung and prostate cancer, referred to the centre for the first time were prerandomised to receive NPIP, mini-NPIP or no information package. Patients randomised to NPIP or mini-NPIP were mailed the information package at least one week before their first appointment. On arrival at the centre, patients were administered the Brief Symptom Inventory (BSI) which measures psychological distress, and interviewed regarding preferences for information and acceptability of the information packages. Of 465 randomised patients, 161 were excluded post-randomisation and 304 completed the entire interview: 100 were randomised to the NPIP, 102 to the mini-NPIP and 102 to the control group. Emotional distress as measured by the BSI was similar for all groups (P = 0.98). Most patients preferred to receive the information (98%), receive it before the first appointment (84%) and by mail (79%). These preferences were more evident for those given the information packages. The majority of patients found the information packages easy to understand (88%) and useful (89%), and no differences were detected between packages. The cost of production and dissemination of NPIP was more than double the cost for mini-NPIP: $ 8.93 vs $ 3.98 (Canadian dollars) per patient. For patients presenting to a cancer centre for the first time, packages of procedural information do not appear to reduce psychological distress, but are preferred by patients. Given the cost of producing NPIP, mini-NPIP is the preferred approach." ]

[ "3285735", "2672899" ]

[ "The use of caffeine in the control of post-anesthetic apnea in former premature infants.", "High-dose caffeine suppresses postoperative apnea in former preterm infants." ]

[ "nan", "Thirty-two former preterm infants (less than or equal to 44 weeks postconceptual age) undergoing inguinal hernia repair were prospectively studied. General inhalational anesthesia with neuromuscular blockade was used. No barbiturates or opioids were given. Infants were randomly divided into two groups. Group 1 received iv caffeine 10 mg/kg immediately after induction of anesthesia. Group 2 received iv saline. Respiratory pattern, heart rate, and SpO2 were monitored using an impedance pneumograph and a pulse oximeter, respectively, for at least 12 h postoperatively. Tracings were analyzed for evidence of apnea, periodic breathing, and/or bradycardia by a pulmonologist unaware of the drug given. None of the patients who received caffeine developed postoperative bradycardia, prolonged apnea, or periodic breathing, and none had postoperative SpO2 less than 90%. In the control group 13 (81%) developed prolonged apnea 4-6 h postoperatively. Fifty percent of the patients had SpO2 less than 90% at the time. This study shows that iv caffeine 10 mg/kg is effective in the control of apnea in otherwise healthy expremature infants between 37 and 44 weeks of postconceptual age. It is still recommended, however, that all infants at risk be monitored for at least 12 h for apnea and bradycardia following general anesthesia." ]

[ "14564258" ]

[ "A new method of immobilization after traumatic anterior dislocation of the shoulder: a preliminary study." ]

[ "This preliminary prospective study was conducted to determine whether immobilization with the arm in external rotation would decrease the rate of recurrence after initial traumatic anterior dislocation of the shoulder. Forty patients with initial shoulder dislocations were assigned to (1) conventional immobilization in internal rotation (IR group, n = 20) or (2) a new method of immobilization in external rotation (ER group, n = 20). The recurrence rate was 30% in the IR group and 0% in the ER group at a mean 15.5 months. The difference in recurrence rate was even greater among those who were aged less than 30 years (45% in the IR group and 0% in the ER group). Immobilization with the arm in external rotation is effective in reducing the rate of recurrence after initial dislocation of the shoulder." ]

[ "12142304", "14508601", "10513500", "15077258", "12022321", "10852980", "11039639", "11114277", "11036846", "11908576", "8782139", "12734907", "3048273", "16030079", "9758073", "12064848", "8140145", "8035399", "11308060", "1395219", "12465163", "11762686", "15695301", "8614771", "13130154", "12665405", "14962965" ]

[ "Prescribed exercise in people with fibromyalgia: parallel group randomised controlled trial.", "Investigation of the effects of pool-based exercise on fibromyalgia syndrome.", "A randomized, controlled trial of exercise and education for individuals with fibromyalgia.", "Long-term efficacy of therapy in patients with fibromyalgia: a physical exercise-based program and a cognitive-behavioral approach.", "A randomized controlled trial of muscle strengthening versus flexibility training in fibromyalgia.", "An observer-blinded comparison of supervised and unsupervised aerobic exercise regimens in fibromyalgia.", "Utilizing exercise to affect the symptomology of fibromyalgia: a pilot study.", "Strength training induced adaptations in neuromuscular function of premenopausal women with fibromyalgia: comparison with healthy women.", "Pool exercise combined with an education program for patients with fibromyalgia syndrome. A prospective, randomized study.", "A randomized clinical trial comparing fitness and biofeedback training versus basic treatment in patients with fibromyalgia.", "An exercise program in the treatment of fibromyalgia.", "Aerobic fitness effects in fibromyalgia.", "A controlled study of the effects of a supervised cardiovascular fitness training program on the manifestations of primary fibromyalgia.", "A randomized clinical trial of an individualized home-based exercise programme for women with fibromyalgia.", "Comparison of integrated group therapy and group relaxation training for fibromyalgia.", "Effects of strength training on muscle strength, cross-sectional area, maximal electromyographic activity, and serum hormones in premenopausal women with fibromyalgia.", "Effects of aerobic exercise on pain perception, affect, and level of disability in individuals with fibromyalgia.", "A randomized, controlled clinical trial of education and physical training for women with fibromyalgia.", "Effects of pool-based and land-based aerobic exercise on women with fibromyalgia/chronic widespread muscle pain.", "The effects of 20 weeks of physical fitness training in female patients with fibromyalgia.", "The effects of exercise and education, individually or combined, in women with fibromyalgia.", "Effect of a randomized, controlled trial of exercise on mood and physical function in individuals with fibromyalgia.", "Spa treatment for primary fibromyalgia syndrome: a combination of thalassotherapy, exercise and patient education improves symptoms and quality of life.", "Effects of aerobic exercise versus stress management treatment in fibromyalgia. A 4.5 year prospective study.", "Changes in knee extension and flexion force, EMG and functional capacity during strength training in older females with fibromyalgia and healthy controls.", "Effects of short versus long bouts of aerobic exercise in sedentary women with fibromyalgia: a randomized controlled trial.", "Fibromyalgia: a randomised, controlled trial of a treatment programme based on self management." ]

[ "To evaluate cardiovascular fitness exercise in people with fibromyalgia.\n Randomised controlled trial. Setting: Hospital rheumatology outpatients. Group based classes took place at a \"healthy living centre.\"\n 132 patients with fibromyalgia.\n Prescribed graded aerobic exercise (active treatment) and relaxation and flexibility (control treatment).\n Participants' self assessment of improvement, tender point count, impact of condition measured by fibromyalgia impact questionnaire, and short form McGill pain questionnaire.\n Compared with relaxation exercise led to significantly more participants rating themselves as much or very much better at three months: 24/69 (35%) v 12/67 (18%), P=0.03. Benefits were maintained or improved at one year follow up when fewer participants in the exercise group fulfilled the criteria for fibromyalgia (31/69 v 44/67, P=0.01). People in the exercise group also had greater reductions in tender point counts (4.2 v 2.0, P=0.02) and in scores on the fibromyalgia impact questionnaire (4.0 v 0.6, P=0.07).\n Prescribed graded aerobic exercise is a simple, cheap, effective, and potentially widely available treatment for fibromyalgia.", "The aim of this study was to compare pool-based exercise and balneotherapy in fibromyalgia syndrome (FMS) patients.\n Fifty female patients diagnosed with FMS according to the American College of Rheumatism (ACR) criteria were randomly assigned to two groups: group 1 (n=25) with pool-based exercise, and in group 2 (n=25) balneotherapy was applied in the same pool without any exercise for 35 min three times a week for 12 weeks. In both groups, pre- (week 0) and post-treatment (weeks 12 and 24) evaluation was performed by one of the authors, who was blind to the patient group. Evaluation parameters included pain, morning stiffness, sleep, tender points, global evaluation by the patient and the physician, fibromyalgia impact questionnaire, chair test, and Beck depression inventory. Statistical analysis was done on data collected from three evaluation stages.\n Twenty-four exercise and 22 balneotherapy patients completed the study. Pretreatment (week 0) measurements did not show any difference between the groups. In group 1, statistically significant improvement was observed in all parameters ( P<0.01) except for the chair test at both weeks 12 and 24. In group 2, week 12 measurements showed significant improvement in all parameters ( P<0.01) except for the chair test and Beck depression inventory. Week 24 evaluation results in group 2 showed significant improvements in pain and fatigue according to visual analogue scale (VAS), 5-point scale, number of tender points, algometric and myalgic scores, and patient and physician global evaluation (P<0.01 and P<0.05, respectively), while improvements were nonsignificant in morning stiffness, sleep, fibromyalgia impact questionnaire (FIQ), chair test, and Beck depression inventory parameters in this group. Comparison of the two groups based on the post-treatment (weeks 12 and 24) percent changes and difference scores relative to pretreatment (week 0) values failed to show a significant difference between the groups for any parameter except Beck depression inventory (P<0.01).\n The results of our study showed that pool-based exercise had a longer-lasting effect on some of the FMS symptoms, but statistical analysis failed to show a significant superiority of pool-based exercise over balneotherapy without exercise. While we believe that exercise is a gold standard in FMS treatment, we also suggest in light of our results that balneotherapy is among the valid treatment options in FMS, and further research regarding the type and duration of the exercise programs is necessary.", "To evaluate the efficacy of a 6-week exercise and educational program for patients with fibromyalgia.\n Forty-one subjects were randomly assigned to the program or served as waiting list controls. Program outcome was assessed with a 6-minute walk test, the Fibromyalgia Impact Questionnaire, a Self-Efficacy Scale, and a \"knowledge\" questionnaire (based on information provided during the educational sessions). Waiting list control subjects subsequently completed the program. Program outcome was reassessed 3 or 6 months post-program.\n The program produced significant improvements in 6-minute walk distance, well-being, fatigue, self-efficacy (for controlling pain and other symptoms), and knowledge. At followup, immediate gains in walk distance, well-being, and self-efficacy were maintained, but gains in fatigue and knowledge were lost.\n Short-term exercise and educational programs can produce immediate and sustained benefits for patients with fibromyalgia. The benefits of our program may be due to exercise or education since both interventions were given.", "To analyze the long-term efficacy of 2 interventions for female fibromyalgia (FM) patients: 1) cognitive-behavioral therapy (CBT), and 2) a physical exercise (PE)-based strategy.\n We conducted a prospective, long-term, randomized, parallel clinical trial. The outcome variables are physical activity, aerobic capacity, and results of the Fibromyalgia Impact Questionnaire (FIQ), Short Form 36, Beck Anxiety and Depression Inventory, Chronic Pain Self-Efficacy Scale, and Chronic Pain Coping Inventory. All were measured at baseline, posttreatment, 6 months, and 1 year. The duration of both treatments was 8 weeks.\n Some items of the FIQ and some strategies to cope with pain improved significantly in both groups after treatment. All variables measuring functional capacity improved significantly in the PE group, whereas only physical activity of the vertebral column improved in the CBT group. There were no differences in anxiety, depression, and self efficacy after treatment in either group. After 1 year of followup, most of the parameters had returned to baseline values in both groups. However, in the PE group, functional capacity remained significantly better.\n PE and CBT improve clinical manifestations in FM patients only for short periods of time. Improvement in self efficacy and physical fitness are not associated with improvement in clinical manifestations.", "To determine the effectiveness of a muscle strengthening program compared to a stretching program in women with fibromyalgia (FM).\n Sixty-eight women with FM were randomly assigned to a 12 week, twice weekly exercise program consisting of either muscle strengthening or stretching. Outcome measures included muscle strength (main outcome variable), flexibility, weight, body fat, tender point count, and disease and symptom severity scales.\n No statistically significant differences between groups were found on independent t tests. Paired t tests revealed twice the number of significant improvements in the strengthening group compared to the stretching group. Effect size scores indicated that the magnitude of change was generally greater in the strengthening group than the stretching group.\n Patients with FM can engage in a specially tailored muscle strengthening program and experience an improvement in overall disease activity, without a significant exercise induced flare in pain. Flexibility training alone also results in overall improvements, albeit of a lesser degree.", "To compare a supervised 12-week aerobic exercise class with unsupervised home aerobic exercises in the treatment of patients with fibromyalgia.\n This was a 48-week randomized single (observer) blind study in a teaching hospital rheumatology and physiotherapy department. The subjects were 74 patients who fulfilled the American College of Rheumatology criteria for fibromyalgia. Results and conclusions. A 12-week exercise class programme with home exercises demonstrated no benefit over a single physiotherapy session with home exercises in the treatment of pain in patients with fibromyalgia. Neither group (nor the groups combined) showed an improvement in pain compared with baseline. There was some significant benefit in psychological well-being in the exercise class group and perhaps a slowing of functional deterioration in this group.", "Fibromyalgia (FM), a rheumatological disorder of unknown origin, is characterized by both physical and psychological symptoms. Although inconclusive results have been reported for most treatment modalities, exercise appears to have universal support for decreasing the myriad of symptoms associated with FM. Weaknesses in the literature, however, prevent conclusive statements regarding exercise prescription and concomitant impact on FM symptomology.\n The current pilot study attempted to examine the effect of a 24-wk walking program at predetermined intensities on FM.\n Initial design was a randomized control trial with high- and low-intensity exercise groups, and a control group. Subsequent nonrandomized control trials were based on actual exercise behavior.\n No differences between initial groups were identified. By collapsing groups, heart rate (HR) decreased (P < 0.05) weeks 0-12. Functional impairments were reduced 54% weeks 0-24, with exercise having a large impact (omega2 = 0.30) on this decrease. By reassigning groups, impact of FM on current health status decreased in the low-intensity group (P < 0.05) and increased in the high-intensity group (P < 0.02) weeks 0-24. Omega squared indicated strong influence of exercise on pain (omega2 = 0.51), with greater pain in the high-intensity group.\n A larger number of subjects and direct supervision of the training program to increase compliance is necessary to clarify the effects of a walking program on the manifestations of FM. Results indicate that intensity of the walking program is an important consideration. Individuals with FM can adhere to low-intensity walking programs two to three times per week, possibly reducing FM impact on daily activities.", "To investigate the effects of 21 weeks' progressive strength training on neuromuscular function and subjectively perceived symptoms in premenopausal women with fibromyalgia (FM).\n Twenty one women with FM were randomly assigned to experimental (FM(T)) or control (FM(C)) groups. Twelve healthy women served as training controls (H(T)). The FM(T) and H(T) groups carried out progressive strength training twice a week for 21 weeks. The major outcome measures were muscle strength and electromyographic (EMG) recordings. Secondary outcome measures were pain, sleep, fatigue, physical function capacity (Stanford Health Assessment Questionnaire), and mood (short version of Beck's depression index).\n Female FM(T) subjects increased their maximal and explosive strength and EMG activity to the same extent as the H(T) group. Moreover, the progressive strength training showed immediate benefits on subjectively perceived fatigue, depression, and neck pain of training patients with FM.\n The strength training data indicate comparable trainability of the neuromuscular system of women with FM and healthy women. Progressive strength training can safely be used in the treatment of FM to decrease the impact of the syndrome on the neuromuscular system, perceived symptoms, and functional capacity. These results confirm the opinion that FM syndrome has a central rather than a peripheral or muscular basis.", "To evaluate the effects of 6 months of pool exercise combined with a 6 session education program for patients with fibromyalgia syndrome (FM).\n The study population comprised 58 patients, randomized to a treatment or a control group. Patients were instructed to match the pool exercises to their threshold of pain and fatigue. The education focused on strategies for coping with symptoms and encouragement of physical activity. The primary outcome measurements were the total score of the Fibromyalgia Impact Questionnaire (FIQ) and the 6 min walk test, recorded at study start and after 6 mo. Several other tests and instruments assessing functional limitations, severity of symptoms, disabilities, and quality of life were also applied.\n Significant differences between the treatment group and the control group were found for the FIQ total score (p = 0.017) and the 6 min walk test (p < 0.0001). Significant differences were also found for physical function, grip strength, pain severity, social functioning, psychological distress, and quality of life.\n The results suggest that a 6 month program of exercises in a temperate pool combined with education will improve the consequences of FM.", "To compare the therapeutic effects of physical fitness training or biofeedback training with the results of usual care in patients with fibromyalgia (FM).\n One hundred forty-three female patients with FM (American College of Rheumatology criteria) were randomized into 3 groups: a fitness program (n = 58), biofeedback training (n = 56), or controls (n = 29). Half the patients in the active treatment groups also received an educational program aimed at improving compliance. Assessments were done at baseline and after 24 weeks. The primary outcome was pain [visual analog scale (VAS)]. Other endpoints were the number of tender points, total myalgic score (dolorimetry), physical fitness, functional ability (Arthritis Impact Measurement Scale and Sickness Impact Profile), psychological distress (Symptom Checklist-90-Revised), patient global assessment (5 point scale), and general fatigue (VAS).\n Baseline scores were similar in all 3 groups. Altogether 25 (17.5%) patients dropped out; they were similarly distributed over all groups: 14 patients after randomization and 11 (8%) during the study. A true high impact level for fitness training was not attained by any patient. After treatment, no significant differences in change scores of any outcome were found between the groups (ANOVA, p > 0.05). All outcome measures showed large variations intra- and interindividually. The educational program did not result in higher compliance with training sessions (62% vs 71%). Analysis of the subgroup of subjects with a high attendance rate (> 67%) also showed no improvement.\n In terms of training intensity and maximal heart rates, the high impact fitness intervention had a low impact benefit. Therefore effectiveness of high impact physical fitness training cannot be demonstrated. Thus compared to usual care, the fitness training (i.e., low impact) and biofeedback training had no clear beneficial effects on objective or subjective patient outcomes in patients with FM.", "To assess the utility of an exercise program, which included aerobic, flexibility and strengthening elements, in the treatment of fibromyalgia (FM). FM is a chronic musculoskeletal condition characterized by diffuse musculoskeletal pain and aching. It has been suggested that aerobic exercise is helpful in its treatment.\n We studied 60 patients who met American College of Rheumatology criteria for FM and had no significant comorbidities. Measurements performed on each patient at the pre and poststudy assessment included the number of tender points (TP), total myalgic scores (TM), aerobic fitness (AF), flexibility and isokinetic strength. After initial evaluation patients were randomly assigned to either an exercise or a relaxation group. Each group met 3 times per week for 6 weeks for 1 h of supervised exercise or relaxation. All patients data were stored in a computerized database and statistical analysis was performed on all pre and poststudy assessments.\n Thirty-eight patients (18 exercise and 20 relaxation) completed the study. Analysis of our data showed no significant difference between the groups in their prestudy assessment. Poststudy assessments, however, showed a significant improvement between the exercise and relaxation groups in TP (p < 0.05), TM (p < 0.05), and AF (p < 0.05). Similar improvements were also found when the pre and poststudy assessment of the exercise group were compared.\n Exercise is helpful in the management of FM in the short term. It also shows that FM patients can undertake an exercise program which includes aerobic, flexibility, and strength training exercises without adverse effects. The long term utility of this type of exercise requires further evaluation.", "To compare 2 exercise modalities, aerobic fitness training and stretching exercises, in patients with fibromyalgia (FM) in relation to function, pain, quality of life, depression, and anxiety, and to correlate the cardiorespiratory fitness gain with symptom improvement.\n Seventy-six women with FM between 18 and 60 years old were randomized to either an aerobic program or stretching program, for 20 weeks. They were evaluated at the beginning of the program and after 10 and 20 weeks in relation to the improvement of aerobic fitness, flexibility, function, Fibromyalgia Impact Questionnaire (FIQ), Short-form Health Survey (SF-36), and depression and anxiety levels. Ventilatory anaerobic threshold (VT) and maximum oxygen uptake (VO2max) were determined by expired gas analyses.\n Aerobic exercise was superior to stretching in relation to VO2 max, VT, function, depression, pain, and the emotional aspects and mental health domains of SF-36. Patients in the stretching group showed no improvement in depression, \"role emotional,\" and \"mental health.\" No association was noted between improvement in aerobic fitness as measured by VT and the improvement of pain, function, or scores in FIQ and SF-36.\n Our results confirm that aerobic exercise is beneficial to patients with FM, but the cardiorespiratory fitness gain is not related to improvement of FM symptoms.", "Forty-two patients with primary fibromyalgia were randomized into a 20-week program consisting of either cardiovascular fitness (CVR) training or simple flexibility exercises (FLEX) that did not lead to enhanced cardiovascular fitness. Patients were supervised by the same medical fitness instructors. Patients in neither group had contact with members of the other group, and were blinded as to the exercise taught to the alternative group. Groups met for 60 minutes 3 times each week. The compliance rate was 90%. Thirty-eight patients completed the study (18 with CVR training and 20 with FLEX). Blind assessments (standardized in preliminary trials to achieve acceptable inter-rater agreement) were performed by the same 2 examiners. After 20 weeks, patients receiving CVR training showed significantly improved cardiovascular fitness scores compared with those receiving FLEX training (t[35] = -4.22, P less than 0.003). Logistic regression analysis showed clinically and statistically significant improvements in pain threshold scores, which were measured directly over fibrositic tender points, in patients undergoing CVR (t[35] = 2.21, P less than 0.04). There was also a trend toward improvement in pain scores (visual analog scale) in the CVR group, but this did not reach statistical significance. There was no improvement in the percentage of body area affected by fibrositic symptoms or the number of nights per week or hours per night of disturbed sleep (self-report inventories). However, compared with the FLEX group, the CVR-trained patients improved significantly in both patient and physician global assessment scores.(ABSTRACT TRUNCATED AT 250 WORDS)", "To determine the efficacy of a 12-week individualized home-based exercise programme on physical functioning, pain severity and psychological distress for women with fibromyalgia (FM).\n Seventy-nine women with a primary diagnosis of FM were randomized to a 12-week individualized home-based moderate-intensity exercise programme or to a usual care control group. Outcomes were functional capacity (Fibromyalgia Impact Questionnaire), pain severity and psychological distress. Outcomes were measured at study entry, at the end of the 12-week intervention, and at 3 and 9 months following completion of the intervention.\n On the basis of intention-to-treat analyses, a significant improvement in functional capacity at 3 and 9 months following treatment for participants in the exercise group who were more functionally disabled at study entry was observed. At both 3 and 9 months post-treatment, the mean estimated benefit of the intervention was more than 10 points [-12.3 (95% CI, -21.9 to -2.8); -10.8 (95% CI, -21.5 to -0.2)]. Compared with the control group, statistically significant improvements in upper body pain were evident in the exercise group at post-treatment. These between-group differences in upper body pain were maintained at 3 and 9 months post-treatment. No statistically significant group differences on lower body pain and psychological distress were found.\n Home-based exercise, a relatively low-cost treatment modality, has the potential to improve important health outcomes in FM.", "The efficacy of an integrated, psychological treatment program was tested in a controlled study involving 27 patients with chronic musculoskeletal pain (fibromyalgia).\n The experimental treatment program consisted of instruction in various self-help techniques (e.g., cognitive behavioral strategies, relaxation, physical exercises) as well as information on chronic pain. Control groups were instructed only in autogenic training. Measures of pain, daily activities, general symptoms, and psychological functioning were assessed before and after treatment, as well as at 4 months after termination of therapy (follow-up).\n At the end of treatment, 7 patients from the experimental group and 2 from the control group showed significant clinical improvement in 3 of 6 parameters (NS). At follow-up, the improvement was still present in 5 experimental cases but in none of the controls (p = 0.024). Successful patients had been sick for a shorter period of time and were less impaired by their condition.\n Psychological interventions in combination with physiotherapy can be effective in treating fibromyalgia patients, especially if applied early.", "To examine the effects of strength training on basal concentrations and acute responses of serum hormones, and their possible interrelationships with training induced muscle hypertrophy and strength gains of the knee extensor muscles in women with fibromyalgia (FM) and healthy controls.\n Twenty-one premenopausal women with FM were randomized to 21 week strength training (FMT; n = 11) or control (FMC; n = 10) groups. Twelve premenopausal sedentary healthy women served as controls (HC). Surface electromyographic (EMG) activity, maximal unilateral isometric force of the right knee extensors, and muscle cross-sectional area (CSA) of the quadriceps femoris throughout the lengths of 3/12 to 12/15 of the femur (Lf) were measured. Serum concentrations of total and free testosterone and growth hormone (GH) were analyzed at rest and in pre- and post-exercise conditions, while levels of insulin-like growth factor and dehydroepiandrosterone sulfate were measured at rest only.\n Mean (SD) maximal force increased by 18% (10%) (p < 0.001) in the FMT group, and by 22% (12%) (p < 0.001) in the HC, while in the FMC it remained unchanged. Maximum integrated EMG of the agonists (VL + VM/2) increased in HC by 22% (p < 0.05) and in the FMT by 19% (p < 0.05). Significant increases in the CSA of the QF were observed at 5 to 12/15 Lf in FMT (p < 0.05-0.01) and at 3 to 12/15 Lf in HC (p < 0.05-0.001), while in FMC the CSA remained unchanged. No training induced changes occurred in the basal concentrations of serum hormones examined. A significant acute increase took place in the mean concentration of GH at pre-training in HC (p < 0.01) and in the FMT (p < 0.05), while at post-training the elevations after the loading (p < 0.001 and 0.05) remained elevated up to 15 min (p < 0.05) in HC and up to 30 min (p < 0.01) post-loading in the FMT.\n Both the magnitude and time course of adaptations of the neuromuscular system to resistance training in women with FM were completely comparable to those taking place in healthy women. Basal levels of the anabolic hormones seem to be similar in women with FM compared to age matched healthy women. Observations recorded during the acute loading conditions might be considered an indication of the training induced adaptation of the endocrine system, showing that the acute GH response may become systematic after strength training in both women with FM and controls.", "The purpose of this study was to evaluate the effect of aerobic walking on the pain, disability, and psychological symptoms of individuals with fibromyalgia.\n Nineteen subjects with fibromyalgia (2 men, 17 women), aged 30 to 69 years (mean = 49.35, SD = 11.83), participated.\n Ten subjects walked 20 minutes, three times per week, for 8 weeks at 60% to 70% of the predicted maximum heart rate for their age. Nine subjects served as sedentary controls. Each subject completed pretests and posttests of the McGill Pain Questionnaire (MPQ), the Sickness Impact Profile (SIP), and the Brief Symptom Inventory (BSI). Due to initial differences on all measures, final scores were adjusted and analyzed by an analysis of covariance.\n The experimental group had lower scores on the MPQ on two of the three BSI indexes, and on the Psychosocial Dimension scale of the SIP, but higher ratings on the Physical Dimension scale of the SIP than did the control group on final testing. Only the differences on one index of the BSI and the Physical Dimension scale of the SIP were significant.\n The results of the study are inconclusive. There were trends suggestive of a beneficial response to aerobic walking (lower psychological and pain ratings) but limited significant findings and higher physical disability ratings, for these individuals with fibromyalgia.", "To determine the effectiveness of self-management education and physical training in decreasing fibromyalgia (FMS) symptoms and increasing physical and psychological well being.\n A pretest-posttest control group design was used. Ninety-nine women with FMS were randomly assigned to 1 of 3 groups; 86 completed the study. The education only group received a 6-week self-management course. The education plus physical training group received the course and 6 h of training designed to assist them to exercise independently. The control group got treatment after 3 months.\n The experimental programs had a significant positive impact on quality of life and self-efficacy. Helplessness, number of days feeling bad, physical dysfunction, and pain in the tender points decreased significantly in one or both of the treated groups when retested 6 weeks after the end of the program. Longterm followup of 67 treated subjects showed significant positive changes on the Fibromyalgia Impact Questionnaire primarily in the physical training group. Among all subjects, 87% were exercising at least 3 times/week for 20 min or more; 46% said they had increased their exercise level since participating in the program; 70% were practicing relaxation strategies as needed; 46% were working at least half time as opposed to 37% at pretest.\n Self-efficacy of the treated groups was enhanced significantly by the program. Other changes were smaller and more delayed than had been expected. Recommendations for future trials include a longer education program, more vigorous physical training, and longterm followup.", "To examine the effects of pool-based (PE) and land-based (LE) exercise programs on patients with fibromyalgia.\n The outcomes were assessed by the Fibromyalgia Impact Questionnaire, the Arthritis Self-Efficacy Scale, and tests of physical capacity.\n Eighteen subjects in the PE group and 16 in the LE group performed a structured exercise program. After 20 weeks, greater improvement in grip strength was seen in the LE group compared with the PE group (P < 0.05). Statistically significant improvements were seen in both groups in cardiovascular capacity, walking time, and daytime fatigue. In the PE group improvements were also found in number of days of feeling good, self-reported physical impairment, pain, anxiety, and depression. The results were mainly unchanged at 6 months followup.\n Physical capacity can be increased by exercise, even when the exercise is performed in a warm-water pool. PE programs may have some additional effects on symptoms.", "During a period of 20 weeks 18 female patients with fibromyalgia participated in a 60-minute exercise program twice a week. A control group, comprising 17 patients, was told not to change their physical activity level. Eleven patients in the training group and fourteen in the control group completed the study. The results at entry were compared to those after 20 weeks, as well as being compared to the results of the control group. No statistically significant changes or differences in general pain, pain coping and fatigue were seen after 20 weeks. Improved dynamic endurance work performance for the upper extremity was found, however, in the training group, measured as the strength of the first (p = 0.01) and the last repetition (p = 0.003). These results differed from the results of the control group (p = 0.02 and p = 0.003). It is concluded that fibromyalgia patients may undergo low-intensity dynamic endurance training without experiencing exacerbation of their general pain and fatigue symptoms.", "To examine the effectiveness of a supervised aerobic exercise program, a self-management education program, and the combination of exercise and education for women with fibromyalgia (FM).\n One hundred fifty-two women were randomized into one of 4 groups: exercise-only, education-only, exercise and education, or control. The duration of the study was 12 weeks. All subjects were analyzed at 3 times: before study, immediately upon completion, and 3 months after completion of the intervention program on measures of disability, self-efficacy, fitness, tender point count, and tender point tenderness. Of the 152 women, complete data were available for 95 and 69 who complied with the protocol. In order to determine the group time interaction, a 2 way analysis of variance with repeated measures was used for each measure.\n The only significant group time interaction was reported with the compliance analysis for the Self-Efficacy Coping with Other Symptoms subscale and the Six Minute Walk. If the program was followed, the combination of a supervised exercise program and group education provided persons with FM with a better sense of control over their symptoms. Fitness improved in the 2 groups undergoing supervised aerobic exercise programs. However, the improvement in fitness was maintained at followup in the exercise-only group and not the combined group. Conclusion. Subjects receiving the combination of exercise and education and who complied with the treatment protocol improved their perceived ability to cope with other symptoms. In addition, a supervised exercise program increased walking distance at post-test, an increase that was maintained at followup in the exercise-only group. Results demonstrate the challenges with conducting exercise and education studies in persons with FM.", "To evaluate the effect of exercise on mood and physical function in individuals with fibromyalgia.\n Subjects were randomly assigned to an exercise (EX) or control (CTL) group. EX subjects participated in 3 30-minute exercise classes per week for 23 weeks. Subjects were tested at entry and at 6, 12, and 23 weeks. Tests included the Beck Depression Inventory (BDI), 6-minute walk, State-Trait Anxiety Inventory (STAI), Mental Health Inventory (MHI), Fibromyalgia Impact Questionnaire (FIQ), Arthritis Self-Efficacy Scale (ASES), and a measure of tender points and knee strength.\n Fifty subjects (27 EX, 23 CTL) completed the study, and 31 (15 EX, 16 CTL) met criteria for efficacy analyses. In efficacy analyses, significant improvements were seen for EX subjects in 6-minute walk distances, BDI (total, cognitive/ affective), STAI, FIQ, ASES, and MHI (3 of 5 subscales) scores. These effects were reduced but remained during intent-to-treat analyses.\n Exercise can improve the mood and physical function of individuals with fibromyalgia.", "To study the effect of a combination of thalassotherapy, exercise and patient education in people with fibromyalgia.\n Patients with fibromyalgia, selected from a rheumatology out-patient department and from members of the Dutch fibromyalgia patient association, were pre-randomized to receive either 2(1/2) weeks of treatment in a Tunisian spa resort, including thalassotherapy, supervised exercise and group education (active treatment) or treatment as usual (control treatment). Primary outcome measure was health-related quality of life, measured with the RAND-36 questionnaire. Secondary measures included the Fibromyalgia Impact Questionnaire, the McGill Pain Questionnaire, the Beck Depression Inventory, tender point score and a 6-min treadmill walk test.\n Fifty-eight participants receiving the active treatment reported significant improvement on RAND-36 physical and mental component summary scales. For physical health, differences from the 76 controls were statistically significant after 3 months, but not after 6 and 12 months. A similar pattern of temporary improvement was seen in the self-reported secondary measures. Tender point scores and treadmill walk tests improved more after active treatment, but did not reach significant between-group differences, except for walk tests after 12 months.\n A combination of thalassotherapy, exercise and patient education may temporarily improve fibromyalgia symptoms and health-related quality of life.", "To determine and compare short- and long-term effects of aerobic exercise (AE), stress management treatment (SMT), and treatment-as-usual (TAU) in fibromyalgia, 60 patients were randomized to 14 weeks of treatment by either AE, SMT or TAU. Outcome measures at baseline, midway through treatment, at treatment completion, and at 4 year follow up included a patient made drawing of pain distribution, dolorimetry of tender points, ergometer cycle test, global subjective improvement, and VAS registrations of: pain, disturbed sleep, lack of energy, and depression. Both AE and SMT showed positive short-term effects. AE was the overall most effective treatment, despite being subject to the most sceptical patient attitude prior to the study. At follow up, there were no obvious group differences in symptom severity, which for AE seemed to be due to a considerable compliance problem.", "To investigate the effects of strength training on neuromuscular functions in elderly females with fibromyalgia (FM).\n Thirteen females with fibromyalgia [group FMt; mean age (s.d.) 60.2 (2.5) years] and 11 healthy controls [group HCt; 64.2 (2.7) yr] carried out supervised strength training twice a week for 21 weeks. Thirteen FM patients [group FMc; 59.1 (3.5) yr] served as non-training controls. Maximal isometric force and electromyographic (EMG) activity of the right quadriceps femoris in knee extension and flexion actions, maximal 10-m walking speed, and 10-step stair-climbing time were measured. Tender points were assessed by palpation, subjectively perceived symptoms with a visual analogue scale, and the self-reported physical function capacity by Health Assessment Questionnaire (HAQ).\n The mean (s.d.) increases in maximal extension force during the training period in groups FMt and in HCt were 32 (33)% (P < 0.001) and 24 (12)% (P < 0.001) respectively and those of flexion were 13 (20)% (P < 0.05) and 24 (17)% (P < 0.01). Explosive force of the extensors increased in both FMt and in HCt. The integrated EMGs of the vastus lateralis and medialis muscles increased in both FMt and HCt. Muscle forces and EMGs in group FMc remained at the basal level. Walking speed, stair-climbing time and the HAQ index improved in group FMt. The changes in the number of tender points and in perceived symptoms were in favour of the training group FMt.\n The data support the hypothesis that elderly female FM patients have normal neuromuscular function. Supervised strength training also suits elderly FM patients, has positive effects on perceived symptoms and improves functional capacity without complications.", "The purposes of this study were: (1) to assess the effectiveness of a 16-week progressive program of home-based, videotape-based, low-impact aerobic exercise on physical function and signs and symptoms of fibromyalgia in previously sedentary women aged 20 to 55 years and (2) to compare the effects of 1 long exercise bout versus 2 short exercise bouts per training day (fractionation) on physical function, signs and symptoms of fibromyalgia, and exercise adherence.\n One hundred forty-three sedentary women were randomly assigned to 1 of 3 groups: a group who trained using a long bout of exercise (LBE group, n=51), a group who trained using short bouts of exercise (SBE group, n=56), and a group who performed no exercise (NE group, n=36).\n The SBE group exercised twice daily, and the LBE group worked out once daily. Both groups progressed in total daily training duration from 10 to 30 minutes, 3 to 5 times a week, for 16 weeks. Physical and psychological well-being, symptoms, and self-efficacy were evaluated using a multivariate analysis of variance.\n Dropout rates for the NE, SBE, and LBE groups were 14%, 38%, and 29%, respectively. The NE group differed from the LBE group in disease severity, self-efficacy, and psychological well-being (midtest, efficacy analysis) and from the SBE group in disease severity and self-efficacy (posttest, efficacy analysis). Exercise adherence was greater for the LBE group than for the SBE group between weeks 5 and 8 of the training program. No other differences between exercise groups were found.\n Progressive, home-based, low-impact aerobics improved physical function and fibromyalgia symptoms minimally in participants who completed at least two thirds of the recommended exercise. Fractionation of exercise training provided no advantage in terms of exercise adherence, improvements in fibromyalgia symptoms or physical function. High attrition rates and problems with exercise adherence were experienced in both exercise groups.", "To evaluate the efficacy of a treatment programme for patients with fibromyalgia (FM) based on self management, using pool exercises and education.\n Randomised controlled trial with a 6 month follow up to evaluate an outpatient multidisciplinary programme; 164 patients with FM were allocated to an immediate 6 week programme (n = 84) or to a waiting list control group (n = 80). The main outcomes were changes in quality of life, functional consequences, patient satisfaction and pain, using a combination of patient questionnaires and clinical examinations. The questionnaires included the Fibromyalgia Impact Questionnaire (FIQ), Psychological General Well-Being (PGWB) index, regional pain score diagrams, and patient satisfaction measures.\n 61 participants in the treatment group and 68 controls completed the programme and 6 month follow up examinations. Six months after programme completion, significant improvements in quality of life and functional consequences of FM were seen in the treatment group as compared with the controls and as measured by scores on both the FIQ (total score p = 0.025; fatigue p = 0.003; depression p = 0.031) and PGWB (total score p = 0.032; anxiety p = 0.011; vitality p = 0.013,). All four major areas of patient satisfaction showed greater improvement in the treatment than the control groups; between-group differences were statistically significant for \"control of symptoms\", \"psychosocial factors\", and \"physical therapy\" No change in pain was seen.\n A 6 week self management based programme of pool exercises and education can improve the quality of life of patients with FM and their satisfaction with treatment. These improvements are sustained for at least 6 months after programme completion." ]

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[ "The impact of health education on frequency and cost of health care use by low income children with asthma.", "Home-based asthma education of young low-income children and their families.", "Randomized trial of a comprehensive asthma education program after an emergency department visit.", "A randomized controlled trial of a pediatric asthma outreach program.", "Impact of a nurse-led home management training programme in children admitted to hospital with acute asthma: a randomised controlled study.", "Effect of a structured asthma education program on hospitalized asthmatic children: a randomized controlled study.", "Asthma education by community child health nurses.", "Delivering tailored asthma family education in a pediatric emergency department setting: a pilot study.", "The pediatric asthma intervention: a comprehensive cost-effective approach to asthma management in a disadvantaged inner-city community.", "Self-management education of children with asthma: AIR WISE.", "A randomized clinical trial to reduce asthma morbidity among inner-city children: results of the National Cooperative Inner-City Asthma Study.", "Asthma at the interface: bridging the gap between general practice and a district general hospital.", "Efficacy of an individualized written home-management plan in the control of moderate persistent asthma: a randomized, controlled trial.", "Structured discharge procedure for children admitted to hospital with acute asthma: a randomised controlled trial of nursing practice.", "Breaking the access barrier: evaluating an asthma center's efforts to provide education to children with asthma in schools.", "Outcomes evaluation of a comprehensive intervention program for asthmatic children enrolled in medicaid.", "Reductions in hospital use from self management training for chronic asthmatics.", "An evaluation of an innovative multimedia educational software program for asthma management: report of a randomized, controlled trial.", "Improved asthma outcomes in a high-morbidity pediatric population: results of an emergency department-based randomized clinical trial.", "A comprehensive inner-city asthma program reduces hospital and emergency room utilization.", "Emergency department allies: a controlled trial of two emergency department-based follow-up interventions to improve asthma outcomes in children.", "Prospective controlled evaluation of the effect of a community based asthma education centre in a multiracial working class neighbourhood.", "Effectiveness of a multicomponent self-management program in at-risk, school-aged children with asthma.", "An educational program for parents of asthmatic preschool children: short- and medium-term effects.", "A controlled trial of an environmental tobacco smoke reduction intervention in low-income children with asthma.", "Asthma in adolescents: a randomized, controlled trial of an asthma program for adolescents and young adults with severe asthma.", "Effectiveness of nebulizer use-targeted asthma education on underserved children with asthma.", "Asthma coaching in the pediatric emergency department.", "Improving follow-up for children with asthma after an acute Emergency Department visit.", "Parental education and guided self-management of asthma and wheezing in the pre-school child: a randomised controlled trial.", "Effectiveness of a nurse-managed program for children with chronic asthma.", "An interdisciplinary intervention for undertreated pediatric asthma." ]

[ "A sample of 310 low income urban children with asthma from 290 families was randomized into a control group and an experimental group that received health education to improve asthma management at home. No significant decreases in subsequent health care use were observed when the experimental group was compared to the control group without regard to previous hospitalization. When the comparison was restricted to children who had been hospitalized during the preceding year, however, the experimental group was found to have decreased its use of the emergency room significantly more than the control group (p less than 0.05) and to have experienced a significantly greater reduction in the mean number of hospitalizations (p less than 0.05) during the year of follow-up. The program reduced health care costs for children with one or more hospitalizations, saving $11.22 for every $1.00 spent to deliver health education.", "To conduct a controlled trial of a home-based education program for low-income caregivers of young children with asthma.\n Participants were randomized to treatment-eight weekly asthma education sessions adapted from the Wee Wheezers program (n = 49)-or usual care (n = 46). Baseline and 3- and 12-month follow-up data were gathered from caregivers and from children's medical records.\n Treatment was associated with less bother from asthma symptoms, more symptom-free days, and better caregiver quality of life at follow-up for children 1-3, but not those 4-6, years of age. Treatment and control groups did not differ in caregiver asthma management behavior or children's acute care utilization.\n This home-based asthma education program was most effective with younger children; perhaps their caregivers were more motivated to learn about asthma management. Targeting psychosocial factors associated with asthma morbidity might also enhance the efficacy of asthma education for these families.", "Patients with asthma who visit the emergency department (ED) may benefit from education that optimizes self-management and treatment.\n To conduct a randomized trial of asthma education (AE) after an ED visit.\n Patients who present with acute asthma and history consistent with moderate to severe persistent asthma or recent ED visits were stratified by age (adult, child) and randomly assigned to intervention or usual care during the ED visit. The intervention was conducted by trained asthma educators and included a facilitated office visit with the primary care physician followed by a home visit. Intention-to-treat analysis was conducted, with time to first asthma relapse (either ED or unscheduled urgent office visit) during the 6-month follow-up period used as the primary outcome.\n Of the 239 patients analyzed, 46% were adults, 46% were male, 30% were African American, and 56% had moderate to severe persistent asthma. Follow-up information was obtained on 191 patients (80%) at 6 months; 23.1% of the intervention group vs 31.1% of the usual care group had an urgent asthma visit (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.48-1.29). Overall, 39% of the 117 patients assigned to the intervention group did not comply with any of the post-ED activities. Subgroup analysis suggested greater benefit among children (HR, 0.62; 95% CI, 0.33-1.19) than adults (HR, 1.08; 95% CI, 0.50-2.33).\n Delivery of a comprehensive AE program after an ED visit was ineffective in adult patients; however, it may be effective in children. Further research on alternative AE delivery strategies appears warranted to reduce the burden of asthma visits to the ED.", "Previous studies have shown that asthma education and case management may reduce asthma emergency care, hospitalizations, and expenditures.\n We sought to study the effect of an asthma outreach program (AOP), a team-based, case-management intervention, on emergency ward (EW) and hospital use.\n Fifty-seven patients aged 1 to 15 years with the diagnosis of asthma based on the usual clinical practice criteria who were continuously enrolled in a staff-model health maintenance organization for a period of at least 2 consecutive years were randomized into 2 intervention groups. The control group received a single intensive asthma education intervention, and the AOP group received the same initial education but then was followed-up by an asthma case management nurse throughout the intervention period.\n EW visits, hospitalizations, and total outside-of-health-plan expenditures (consisting of EW and hospital expenses, as well as miscellaneous costs, such as ambulance, durable medical equipment, tertiary referrals, and home care) were assessed from claims filed for a year before and after enrollment. Control group patients experienced significant reductions in EW visits (39%), hospitalizations (43%), and outside-of-health-plan costs (28%), possibly as a result of the baseline educational intervention received by all enrolled patients, in conjunction with regression to the mean. AOP group patients experienced significant reductions in EW visits, (73%, P =.0002), hospitalizations (84%, P =.0012), and outside-of-health-plan use (82%, P <.0001). When compared with the control group, AOP group patients demonstrated additional significant reductions in EW visits (57%, P <.05), hospitalizations (75%, P <.05), and outside-of-health-plan use (71%, P <.001). Estimates of direct savings to the health plan ranged from $7.69 to $11.67 for every dollar spent on the AOP nurse's salary, depending on assumptions.\n Asthma patients in a staff-model health maintenance organization decreased their resource use between 57% to 75% by participation in an AOP as compared with a randomized control group receiving only an educational intervention. Substantial savings were achieved compared with the cost of the AOP nurse.", "Re-admissions to hospital in childhood asthma are common with studies reporting that 25% or more of children will be re-admitted within a year. There is a need for strategies to reduce re-admissions.\n A prospective randomised control study of an asthma home management training programme was performed in children aged two years or over admitted with acute asthma. Two hundred and one children were randomised at admission to either an intervention group (n = 96) which received the teaching programme or a control group (n = 105). A nurse-led teaching programme used the current attack as a model for the management of future attacks and included discussion, written information, subsequent follow up and telephone advice aimed at developing and reinforcing individualised asthma management plans. Parents were also provided with a course of oral steroids and guidance on when to start them.\n The groups were similar in degree of social deprivation, length of stay, number of previous admissions, acute asthma treatment, and asthma treatment at discharge. Subsequent re-admissions were significantly reduced in the intervention group from 25% to 8% in individual follow up periods that ranged from two to 14 months (chi 2 = 9.63; p = 0.002). This reduction was not accompanied by any increase in subsequent emergency room attendances nor, in the short term, by any increase in urgent community asthma treatment. The intervention group also showed significant reductions in day and night morbidity 3-4 weeks after admission to hospital.\n A nurse-led asthma home management training programme administered during a hospital admission can significantly reduce subsequent admissions to hospital for asthma. Acute hospitalisation may be a particularly effective time to deliver home management training.", "The aim of this study was to compare the effectiveness of an intensive asthma education program (group B) with that of a standard asthma education program (group A).\n A prospective randomized single blinded study was conducted in the pediatric department of a public hospital in Hong Kong. Children aged 2-15 years admitted to the pediatric department with an acute attack of asthma were recruited. A standard asthma education program (group A) or an intensive asthma education program (group B) for children were offered. The main outcome measures include the number of visits to the emergency department and the number of hospitalization for asthma during the 3 month follow-up period.\n A total of 45 children were in group A and 55 in group B. Group B had statistically significant reductions in the number of visits to the emergency department and the number of hospitalizations. Drug compliance was also significantly improved in group B. Parents' satisfaction rate was also higher in group B.\n The intensive asthma education program might be more cost effective than the standard asthma education program in the management of asthmatic children admitted to hospital in Hong Kong.", "A randomised controlled study of an educational programme for children with asthma and their families was carried out by community child health nurses. Three hundred and sixty eight children aged 2 to 14 years were enrolled in the study after admission to hospital for asthma. The intervention group was visited monthly by a nurse for six months. The subjects were assessed six months later by a postal, self administered questionnaire. European children in the intervention group were taking significantly more drugs for the treatment of asthma six months after the index admission to hospital than those in the control group (mean (SD) intake 2.7 (1.1) v 2.1 (1.0), respectively). In particular, they were using more theophylline (56.6% v 37.0%) and inhaled steroids (34.9% v 21.0%). There was no difference between the groups for parental reports of improvement, of missed schooling, and in severe attacks of asthma of not responding to the usual treatment at home. European children in the intervention group used the hospital services for severe attacks of asthma more than controls (34.2% v 10.5%). There were more re-admissions in the European intervention group in the subsequent six months after the index admission than in the control group (mean (SD) 0.51 (0.97) v 0.29 (0.65). Re-admission continued to be higher in the 12 months after the nurse had stopped visiting (0.81 (1.65) v 0.25 (0.65]. There was no difference in the duration of hospital stay between the intervention and control groups. For Polynesian children there was no difference between the groups for any outcome measures.", "Many children are brought to the pediatric emergency department (ED) with acute asthma symptoms. Emergency asthma care is costly, and many ED visits may be preventable. Families often do not have written asthma action plans and lack asthma self-management skills. This study tests a tailored self-management intervention delivered in the ED for families of children with asthma. The primary hypotheses were that the intervention group would have greater confidence to manage asthma 14 days postintervention and more well-asthma visits and fewer urgent care/ED visits at 9 and 12 months.\n This randomized intervention/usual-care study was part of a larger ED asthma surveillance project in 4 urban pediatric ED sites. Asthma educators used a computer-based resource to tailor the intervention messages and provide a customized asthma action plan and educational summary. Children with acute asthma were enrolled during an ED visit, and follow-up telephone interviews were conducted during the next 9 months. The ED clinician classified the child's acute and chronic severity.\n To date, 464 subjects aged 1 to 18 years have been enrolled. The ED clinicians reported that 46% had intermittent and 54% had persistent chronic severity with 51% having mild acute severity episodes. The confidence level to prevent asthma episodes and keep them from getting worse was significantly higher in the intervention group at 14 days postintervention. More subjects in the intervention group reported well-asthma visits by 9 months. Return ED visits were significantly lower in the intervention group in those with intermittent asthma. Twelve-month follow-up is in process.\n The tailored ED self-management intervention demonstrates significant effects on caregiver self-confidence and well-visit follow-up. Additional evaluation is needed to determine what impact this intervention has long-term.", "To compare three pediatric asthma interventions for their impact on improving the health status of inner-city asthmatic children and in achieving cost savings.\n A total of 212 children 1 to 16 years of age were randomized into three groups: group 1 (n = 74) received one individualized asthma education session; group 2 (n = 68) received reinforced asthma education; group 3 (n = 70) received reinforced asthma education plus case management. Asthma-related health resource utilization and cost were primary outcomes. The cost-benefit analysis sought to estimate the expected cost savings to the Illinois Department of Healthcare and Family Services (Medicaid administrator) associated with the intervention.\n Participants in all three groups used significantly fewer emergency health care services in the follow-up year. Averaged across all three groups, the magnitudes of declines were substantial: 81% for hospitalizations, 69% for hospital days, 64% for emergency department visits, and 58% for clinic visits. Although there were no statistically significant differences between study groups for three of the four main outcome measures, group 3 participants consistently improved to the greatest degree. All three interventions were associated with considerable cost savings ranging from $4,021/child/year for group 1 to $4,503/child/year for group 3.\n Asthma education with or without case management services enhances the health of children with asthma thereby reducing associated costs.", "This study was conducted to test the efficacy of AIR WISE, an individually administered asthma self-management program. Subjects were paired and randomly assigned to either an experimental group (N = 7) or a control group (N = 7). The frequency of experimental group emergency visits, analyzed over a 12-month posttreatment period, was substantially less than those of the control group, supporting the hypothesis that AIR WISE is effective in high-utilizer children through improved self-management.", "To evaluate a family-focused asthma intervention designed for inner-city children 5 to 11 years old with moderate to severe asthma.\n Randomized, multisite, controlled trial to minimize symptom days (wheeze, loss of sleep, reduction in play activity) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period. The intervention was tailored to each family's individual asthma risk profile assessed at baseline.\n Averaged over the first 12 months, participants in the intervention group (n = 515) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06 symptom days for the control group (n = 518), a difference of 0.55 (95% CI, 0.18 to 0.92, P =.004). The reduction among children with severe asthma was approximately 3 times greater (1.54 d/2 wk). More children in the control group (18.9%) were hospitalized during the intervention compared with children in the intervention group (14. 8%), a decrease of 4.19% (CI, -8.75 to 0.36, P =.071). These improvements were maintained in the intervention group during the second year of follow-up, during which they did not have access to the asthma counselor.\n We demonstrated that an individually tailored, multifaceted intervention carried out by Masters-level social workers trained in asthma management can reduce asthma symptoms among children in the inner city.", "A clinic supervised by a nurse, using principles originally developed in general practice, was established in the paediatric department of a district general hospital. A randomised controlled study was conducted comparing children admitted with asthma or attending outpatients who were given a patient education programme and self management plan (intervention group) with a control group. The study comprised 91 patients aged 3-14 years admitted for asthma or attending a hospital outpatient department from November 1989 to November 1990. Seventy seven patients completed the study and kept diaries for a median of 283 days. Patients in the intervention group had significantly less restriction of activity (95% confidence interval (CI) -0.27 to -0.01) and fewer episodes of peak flow below 30% of best (95% CI 0.03 to 1.17). Patients in the intervention group were more likely to make the correct response to an acute exacerbation of their asthma than the control group (71% v 47%, 95% CI 9.51 to 39.1). The intervention group had fewer school absences and fewer home visits by a general practitioner. There was an increase in the readmission rate for the intervention group. A subgroup of patients who self managed by doubling their use of inhaled steroids during an exacerbation performed better than those patients who only increased their bronchodilator or were managed on salbutamol or sodium cromoglycate alone. Improvements in patient follow up and the structure of the self management plans used, particularly changing the peak flow level at which inhaled steroids are doubled, may further improve the outcome of patients attending the asthma clinic.", "The management of childhood asthma necessitates a comprehensive approach including pharmacological treatment as well as education about self-evaluation and home management of the condition.\n To evaluate the efficacy of adding an individualized written home-management plan in the control of moderate persistent asthma.\n Children with moderate persistent asthma were randomized to receive either an individualized written home-management plan or no plan, in addition to standard asthma therapy including education. They were followed up with serial measurement of outcome variables.\n Children receiving an individualized written home-management plan had fewer acute asthma events, fewer lost school days, lower symptom score and less nocturnal awakening than those who did not receive a written plan.\n The addition of a written individualized home-management plan improves overall control in children with moderate persistent asthma.", "Discharge planning is becoming an important part of the management of childhood asthma in hospital. Readmission to hospital, although often inevitable, might represent a failure of the opportunity for intervention presented by a brief period of supervised care in hospital.\n To examine the impact of a structured, nurse-led discharge package for children admitted to hospital with acute asthma on readmission to hospital, reattendance at the accident and emergency (A&E) department, and general practitioner consultations for asthma.\n A structured nurse-led discharge package, consisting of a 20 minute patient education programme and self management plan for children with asthma was developed on the wards of a busy children's hospital. A randomised controlled trial was conducted involving 160 children aged 2-16 years admitted for asthma over a 12 month period. Readmission and A&E reattendance's over the six months after discharge from hospital were obtained from the hospital computerised information system and general practitioner consultations from practice records.\n Children in the intervention group were significantly less likely to be readmitted to hospital in the next six months than those in the control group (12 of 80 v 30 of 80 patients), and significantly less likely to attend the A&E department (6 of 80 v 31 of 80). Significantly fewer children in the intervention group had visits to their general practitioner for problematic asthma (31 of 78 v 72 of 77 for whom data were available).\n By delivering the simplest form of education and support during a child's stay in hospital, readmissions over a six month period were reduced. The programme was designed to be suitable for administration by nursing staff on the children's wards after a brief period of training.", "To evaluate an asthma education program for children with asthma that is delivered in their school by certified asthma educators from a local hospital-based asthma center.\n Randomized controlled trial.\n Twenty-six elementary schools located in a suburb of Toronto.\n A total of 256 children in grades 2 to 5 with asthma and their parents were randomized to control and experimental groups.\n Children in the experimental group received the \"Roaring Adventures of Puff\" asthma education program over the course of six weekly 1-h sessions. Those in the control group continued receiving usual care.\n Data collection involved measuring asthma quality of life, self-efficacy for managing asthma, school absenteeism, days of interrupted activity, health services use, and parental loss of time from work. Quality of life and self-efficacy data were collected from the children at baseline and 2 months. Telephone parental interviews conducted over 1 year were used to collect data on the remaining variables. Unpaired t test, analysis of variance, and chi2 test were used to determine whether differences existed between the groups. The results are reported as the mean +/- SD. The experimental group demonstrated higher scores than the control group for self-efficacy (3.6 +/- 0.7 vs 3.8 +/- 0.9, respectively; p < 0.05) and quality of life (5.0 +/- 1.4 vs 5.5 +/- 1.4, respectively; p < 0.05). At 1 year, the experimental group demonstrated fewer mean urgent health-care visits (2.5 +/- 2.5 vs 1.7 +/- 1.9 visits per year, respectively; p < 0.01), days of missed school (4.3 +/- 5.7 vs 3.0 +/- 4.4 days per year, respectively; p > 0.05), and days of interrupted activity (9.1 +/- 10.5 vs 6.2 +/- 7.3 days per year; p < 0.01) related to asthma than the control group. There were no differences between the groups for parental work absenteeism or scheduled asthma visits.\n Providing an asthma education program to children in their school can significantly improve quality of life and reduce the burden of childhood asthma.", "To evaluate health care and financial outcomes in a population of Medicaid-insured asthmatic children after a comprehensive asthma intervention program.\n Controlled clinical trial.\n Pediatric allergy clinic in an urban, tertiary care children's hospital.\n Eighty children, 2 to 16 years old, with a history of frequent use of emergent health care services for asthma. Intervention. Children in the intervention group received asthma education and medical treatment in the setting of a tertiary care pediatric allergy clinic. An asthma outreach nurse maintained monthly contact with the families enrolled in the intervention group.\n Emergency department (ED) visits, hospitalizations, and health care charges per patient in the year after enrollment.\n Baseline demographics did not differ significantly between the 2 groups. In the year before the study, there were no significant differences between intervention and control children in ED visits (mean, 3.5 per patient), hospitalizations (mean,.6 per patient) or health care charges ($2969 per patient). During the study year, ED visits decreased to a mean of 1.7 per patient in the intervention group and 2.4 in controls, while hospitalizations decreased to a mean of.2 per patient in the intervention group and.5 in the controls. Average asthma health care charges decreased by $721/child/year in the intervention group and by $178/patient/year in the control group.\n A comprehensive asthma intervention program for Medicaid-insured asthmatic children can significantly improve health outcomes while reducing health care costs.asthma education, health care outcomes, Medicaid, asthma outreach, utilization.", "The purpose of this study was to assess the impact of asthma Self Management Training on the health status and resource use of patients with chronic asthma. The study consisted of a randomized control design of chronic asthmatic patients in a tertiary care center in India. The intervention group (153 patients) received four training sessions in addition to the regular care provided to the control group (150 patients). Health status and resource use were measured at baseline and over a one year follow-up period. The intervention group had significantly better health status (measured by breathing ability), fewer productive days lost, and lower resource use (hospitalizations and emergency room visits) than the control group. Total annual costs (direct and indirect) were also lower, though physician costs were not included in the assessment. Therefore, incorporation of asthma Self Management Training as part of clinical management of asthma can result in improvements in health status and reductions in hospital use.", "Asthma continues to be a substantial cause of morbidity in pediatric populations. New strategies are needed to provide cost-effective educational interventions for children with asthma, particularly those in the inner city.\n To assess the effectiveness of a multimedia educational software program about asthma.\n A hospital-based primary care clinic and an affiliated neighborhood health center.\n Randomized, controlled trial.\n Children 3 to 12 years old with physician-diagnosed asthma.\n An interactive educational computer program, Asthma Control, designed to teach children about asthma and its management. Using a graphic display of a child going through simulated daily events, the game emphasizes: 1) monitoring; 2) allergen identification; 3) use of medications; 4) use of health services; and 5) maintenance of normal activity. Control group participants reviewed printed educational materials with a research assistant.\n Acute health care use (emergency department and outpatient) was the primary outcome. Secondary outcome measures included maternal report of asthma symptom severity, child functional status and school absences, satisfaction with care, and parental and child knowledge of asthma.\n A total of 137 families were enrolled in the study (76 intervention, 61 control). Both intervention and control groups showed substantial improvement in all outcomes during the 12-month follow-up period. Aside from improvement in knowledge after use of the computer program, no differences were demonstrated between the 2 groups in primary or secondary outcome measures. Children reported enjoyment of program use.\n This trial of an educational software program found that it did not produce greater improvement than occurred with review of traditional written materials. Because both groups showed substantial improvement over baseline, computer-based education may be more cost-effective. Alternatively, improvements in illness severity over time may overshadow the effects of such interventions. Rigorous comprehensive evaluations such as this are necessary to assess new interventions intended to improve management and outcomes of asthma.", "To determine if an emergency department-based asthma follow-up clinic could improve outcomes within a high-morbidity pediatric population.\n Prospective, randomized clinical trial with 6 months of follow-up.\n Emergency department of an urban pediatric medical center.\n Convenience sample of 488 patients aged 12 months to 17 years, inclusive, with prior physician-diagnosed asthma and 1 or more other unscheduled visits in the previous 6 months and/or 1 or more hospitalizations in the prior 12 months.\n Single follow-up clinic visit focusing on 3 domains: asthma self-monitoring and management, environmental modification and trigger control, and linkages and referrals to ongoing care.\n The primary outcome measure was unscheduled visits for acute asthma care. Secondary outcomes included compliance with a medical plan and asthma quality of life. Analysis was by intention to treat with adjustment for baseline differences.\n Of those randomized to the clinic visit, 172 (70.5%) of 244 attended. The intervention group had significantly fewer mean unscheduled visits for asthma care during follow-up (1.39 vs 2.34; relative risk [RR] = 0.60 [95% confidence interval (CI), 0.46-0.77]). At 6 months, significantly more patients in the intervention group reported use of inhaled corticosteroids in the prior 2 days (49.3% vs 26.5%; RR = 2.03 [95% CI, 1.57-2.62]), no limitation in daytime quality of life (43.8% vs 34.4%; RR = 1.36 [95% CI, 1.06-1.73]), and no functional limitations in quality of life (49.8% vs 40.8%; RR = 1.33 [95% CI, 1.08-1.63]).\n Attendance in the follow-up clinic was high. The intervention decreased subsequent unscheduled health care use while improving compliance and quality of life.", "To evaluate the efficacy of a comprehensive asthma program on emergency department (ED) visits and hospital admission rates in an inner-city pediatric population.\n A12-month prospective randomized trial.\n Three hundred asthma patients, ages 2 to 17 years, were recruited and randomized in an inner-city pediatric ED, to obtain asthma care in a specialty clinic or to continue receiving care by other health resources. The specialty clinic provided intensive medical and environmental control, education, close monitoring, and 24-hour availability. For the prospective study, monthly questionnaires were sent to the caregivers of these children to evaluate use of hospital facilities for asthma care. For the retrospective study, use of hospital resources by the study participants was analyzed using a hospital database.\n One hundred twenty-nine patients (60 in the treatment group and 69 in the control group) were included in the final analysis. Asthma severity index was significantly higher for the patients in the treatment versus the control group (35% versus 16.2%, P = .05). Fewer patients in the treatment group visited the ED at least once during the first study year, 32 versus 46, (P = .11), and they made fewer visits, 73 versus 269. The mean number of ED visits of the patients who used the ED was 0.1 versus 0.326 for the control group (P = .01). There were also fewer admissions in the treatment group, 22 versus 29 (P < .59). The 53 patients remaining in the treatment group in the second study year made fewer visits to the ED versus the control group (P < .03). In comparison to the first year, fewer patients in the treatment group visited the ED or were hospitalized in the second year (P = .007 and P = .04, respectively).\n A comprehensive asthma care program is efficacious in reducing hospital utilization.", "We sought to study the impact of emergency department (ED)-based intensive primary care linkage and initiation of asthma case management on long-term, patient-oriented outcomes for children with an asthma exacerbation.\n Our study was a randomized, 3-arm, parallel-group, single-blind clinical trial. Children aged 2 through 17 years treated in a pediatric ED for acute asthma were randomly assigned to standard care (group 1), including patient education, a written care plan, and instructions to follow up with the primary care provider within 7 days, or 1 of 2 interventions. Group 2 received standard care plus assistance with scheduling follow-up, while group 3 received the above interventions, plus enrollment in a case management program.\n The primary outcome was the proportion of children having an ED visit for asthma within 6 months. Other outcomes included change in quality-of-life score and controller-medication use.\n Three hundred fifty-two children were enrolled; 78% completed follow-up, 69% were black, and 70% had persistent asthma. Of the children, 37.8% had a subsequent ED visit for asthma, with no difference among the treatment groups (group 1: 38.4%; group 2, 39.2%; group 3, 35.8%). Children in all groups had a substantial, but similar, increase in their quality-of-life score. Controller-medication use increased from 69.4% to 81.4%, with no difference among the groups.\n ED-based attempts to improve primary care linkage or initiate case management are no more effective than our standard ED care in improving subsequent asthma outcomes over a 6-month period.", "Previous work has indicated a high rate of non-attendance at hospital based clinics among young, multiracial asthmatic patients of lower socioeconomic class. The efficacy of delivering asthma education from a community health centre established in a multiracial working class neighbourhood was evaluated.\n A prospective controlled study was performed in which asthmatic subjects aged between two and 55 years attending a hospital emergency room with acute asthma and living within a defined geographical area of high emergency room users were randomised to the usual follow up or the education centre plus usual follow up. Measurements were taken at entry into the study and again nine months later.\n At nine months patients randomised to the education centre had more preventive medications, more peak expiratory flow meters and better flow meter technique, more self-management plans, better knowledge of appropriate action to take when confronted with worsening asthma, less nocturnal awakening, and better self-reported asthma control than the control group. There was no difference between the study groups in measurements of compliance, hospital admission, days lost from school or work, or emergency room use.\n The main effects of education were on asthma knowledge and self-management skills, whilst improvements in asthma morbidity were small. Potential reasons for this include heterogeneous study population (in terms of baseline self-management skills, asthma severity, ethnicity and age), pragmatic study design, insensitivity of many of the measurements of morbidity, the modest effectiveness of a single time limited education programme, and inability to limit the effects of such a large community based study to the intervention group (there was a 67% reduction in asthma admissions during the study period from the geographical area targeted compared with a 22% reduction for the rest of Auckland).", "Improving asthma knowledge and self-management is a common focus of asthma educational programs, but most programs have had little influence on morbidity outcomes. We developed a novel multiple-component intervention that included the use of an asthma education video game intended to promote adoption of asthma self-management behaviors and appropriate asthma care.\n To determine the effectiveness of an asthma education video game in reducing morbidity among high-risk, school-aged children with asthma.\n We enrolled 119 children aged 5 to 12 years from low-income, urban areas in and around San Francisco, CA, and San Jose, CA. Children with moderate-to-severe asthma and parental reports of significant asthma health care utilization were randomized to participate in the disease management intervention or to receive their usual care (control group). Patients were evaluated for clinical and quality-of-life outcomes at weeks 8, 32, and 52 of the study.\n Compared with controls, the intervention group had significant improvements in the physical domain (P = .04 and P = .01 at 32 and 52 weeks, respectively) and social activity domain (P = .02 and P = .05 at 32 and 52 weeks, respectively) of asthma quality of life on the Child Health Survey for Asthma and child (P = .02 at 8 weeks) and parent (P = .04 and .004 at 32 and 52 weeks, respectively) asthma self-management knowledge. There were no significant differences between groups on clinical outcome variables.\n A multicomponent educational, behavioral, and medical intervention targeted at high-risk, inner-city children with asthma can improve asthma knowledge and quality of life.", "Parent education has proven to be effective in improving parents coping with their child's asthma. Little is known about its effectiveness neither during inpatient rehabilitation nor about the different effectiveness of different approaches. A controlled clinical trial was conducted with 242 parents of asthmatic children aged less than 8 years. The aims were to develop a cognitive-behavioral training program for parents and compare its differential effectiveness with an information-centered standard-program as part of rehabilitation. Both groups reported a highly significant increase in their knowledge, self-efficacy and quality of life over time in a follow-up just after the end of their inpatient stay. There was a further increase from discharge to the 6-month follow-up for self-efficacy and quality of life. In respect to the functional severity of asthma, children of both groups showed a significant improvement. Whether these effects have long-term stability and which parents benefit from which type of intervention will be the objective of an ongoing 12-month follow-up.", "To determine the effectiveness of a cotinine-feedback, behaviorally based education intervention in reducing environmental tobacco smoke (ETS) exposure and health-care utilization of children with asthma.\n Randomized controlled trial of educational intervention vs usual care.\n The pediatric pulmonary service of a regional pediatric hospital.\n ETS-exposed, Medicaid/Medi-Cal-eligible, predominantly minority children who were 3 to 12 years old and who were seen for asthma in the hospital's emergency, inpatient, and outpatient services departments (n = 87).\n Three nurse-led sessions employing behavior-changing strategies and basic asthma education and that incorporated repeated feedback on the child's urinary cotinine level.\n The primary measurements were the urinary cotinine/creatinine ratio (CCR) and the number of acute asthma medical visits. The secondary measurements were number of hospitalizations, smoking restrictions in home, amount smoked, reported exposures of children, and asthma control.\n The intervention was associated with a significantly lower odds ratio (OR) for more than one acute asthma medical visit in the follow-up year, after adjusting for baseline visits (total visits, 87; OR, 0.32; p = 0.03), and a comparably sized but nonsignificant OR for one or more hospitalization (OR, 0.34; p = 0.14). The follow-up CCR measurement and the determination of whether smoking was prohibited inside the home strongly favored the intervention group (n = 51) (mean difference in CCR adjusted for baseline, -0.38; p = 0.26; n = 51) (60; OR [for proportion of subjects prohibiting smoking], 0.24; p = 0.11; n = 60).\n This intervention significantly reduced asthma health-care utilization in ETS-exposed, low-income, minority children. Effects sizes for urine cotinine and proportion prohibiting smoking were moderate to large but not statistically significant, possibly the result of reduced precision due to the loss of patients to active follow-up. Improving ETS reduction interventions and understanding their mechanism of action on asthma outcomes requires further controlled trials that measure ETS exposure and behavioral and disease outcomes concurrently.", "Asthma is common and is often poorly controlled in adolescent subjects.\n To determine the impact of an age-specific asthma program on asthma control, particularly on exacerbations of asthma requiring emergency department treatment, and on the quality of life of adolescents with asthma.\n The present randomized, controlled trial included patients who were 15 to 20 years of age and had visited emergency departments for management of their asthma. The interventional group attended an age-specific asthma program that included assessment, education and management by a team of asthma educators, respiratory therapists and respiratory physicians. In the control group, spirometry was performed, and the patients continued to receive usual care from their regular physicians. The outcomes were assessed by a questionnaire six months after entry into the study.\n Ninety-three subjects entered the study and were randomly assigned to the intervention or control group. Of these, only 62 patients were available for review after six months. Subjects in both the control and the intervention groups showed a marked improvement in their level of asthma control, reflected primarily by a 73% reduction in the rate of emergency department attendance for asthma. Other indexes of disease control, including disease-specific quality of life, as assessed by questionnaires, were improved. There was, however, no discernible difference between the subjects in the two groups, with the exception of an improvement in favour of the intervention group in the symptom (actual difference 0.7, P=0.048) and emotional (actual difference 0.8, P=0.028) domains of the asthma quality of life questionnaire. The overall quality of life score favoured the intervention group by a clinically relevant difference of 0.6, but this difference did not reach statistical significance (P=0.06).\n Although all subjects demonstrated a significant improvement in asthma control and quality of life, the improvement attributable to this intervention was limited to two domains in disease-specific quality of life.", "To determine the effectiveness of a home-based asthma education intervention in increasing appropriate nebulizer use and reducing symptom frequency, emergency department (ED) visits, and hospitalizations over 12 months.\n A randomized clinical trial. Settings Pediatric primary care, pulmonary/allergy, and ED practices associated with the University of Maryland Medical System and The Johns Hopkins Hospital, Baltimore.\n Children with persistent asthma, aged 2 to 9 years, with regular nebulizer use and an ED visit or hospitalization within the past 12 months. Children were randomized into the intervention (n = 110) or control (n = 111) group. Follow-up data were available for 95 intervention and 86 control children.\n Home-based asthma education, including symptom recognition, home treatment of acute symptoms, appropriate asthma medication, and nebulizer practice.\n Estimates of mean differences in asthma symptom frequency, number of ED visits and hospitalizations and appropriate quick relief, controller medication, and nebulizer practice over 12 months.\n Of the 221 children, 181 (81.9%) completed the study. There were no significant differences in home nebulizer practice, asthma morbidity, ED visits, or hospitalizations between groups (P range, .11-.79). Although most children received appropriate nonurgent asthma care (mean, 2 visits per 6 months), more than one third of all children received at least 6 quick-relief medication prescriptions during 12 months, with no difference by group.\n A nebulizer education intervention had no effect on asthma severity or health care use. Of concern is the high quick-relief and low controller medication use in young children with asthma seen nearly every 3 months for nonurgent care.", "Coaching and monetary incentives have been used to modify medical behavior of individuals with several chronic diseases, including asthma. The authors performed a randomized, controlled trial of an intervention combining asthma coaching during an emergency department (ED) visit for asthma, and monetary incentive to improve follow-up with primary care providers (PCP).\n Subjects were parents of children 2-12 years of age, with Medicaid or no medical insurance, receiving treatment for asthma in the ED. The primary outcome was a verified PCP visit for asthma within two weeks of the index ED visit. All parents received 15 dollars for their time in the ED. Parents in the intervention group were told that they would receive an additional 15 dollars monetary incentive if a PCP visit was completed. The coach engaged in a dialogue with the parent during the ED visit, and discussed the importance and advantages of seeking follow-up care with the child's PCP. All parents received the usual discharge instructions, including advice to see the PCP within three days.\n The authors enrolled 92 parents; outcome data were available for 86 (42 controls, 50 intervention). Demographic characteristics were similar in both groups. There was no significant difference in the proportion of patients who had follow-up PCP visits between the intervention (22.0%; 95% confidence interval [95% CI] = 11.5% to 36.0%) and control (23.8%; 95% CI = 12.0% to 39.4%) groups (p = 0.99).\n An intervention combining asthma coaching during acute ED visits and a monetary incentive to return for a PCP visit does not appear to increase follow-up with the PCP.", "To improve follow-up with primary care providers after acute Emergency Department (ED) asthma visits for children from low-income urban families.\n A prospective, randomized, controlled trial evaluated combined telephone asthma coaching and monetary incentive. The primary outcome was asthma-planning visits with primary care providers within 15 days of index ED visits. The subjects were urban parents whose children were treated for asthma in the ED and had Medicaid or no insurance.\n We enrolled 527 parents (264 control and 263 intervention). There was a significant difference ( P < .0001) between the intervention (35.7%) and control (18.9%) groups in the proportion of children who had asthma-planning visits and decreased mean nights/days with asthma symptoms by 4.36 intervention and 3.31 control at 2 weeks. The proportions of children with asthma-planning visits and acute asthma care visits during the 16-day to 6-month period were similar for both groups.\n Telephone coaching and a monetary incentive significantly increased the proportion of low-income urban parents who brought their children for asthma-planning visits, and decreased asthma symptoms shortly after asthma ED visits. The intervention did not increase subsequent asthma-planning visits or decrease ED visits or hospitalizations.", "The effects on morbidity were examined of providing an educational intervention and a written guided self-management plan to the parents of pre-school children following a recent attendance at hospital for asthma or wheeze.\n A prospective, randomised, partially blinded, controlled trial was designed at two secondary care centres. Over a 13 month period 200 children aged 18 months to 5 years at the time of admission to a children's ward or attendance at an accident and emergency department or children's (emergency) assessment unit (A&E/CAU) with a primary diagnosis of acute severe asthma or wheezing were recruited. 101 children were randomised into the control group and received usual care and 99 were assigned to the intervention group and received: (1) a pre-school asthma booklet; (2) a written guided self-management plan; and (3) two 20 minute structured educational sessions between a specialist respiratory nurse and the parent(s) and child. Subjects were assessed at 3, 6, and 12 months. The main outcomes were GP consultation rates, hospital re-admissions, and attendances at A&E/CAU. Secondary outcomes included disability score, caregivers' quality of life, and parental knowledge of asthma.\n There were no statistically significant differences between the two groups during the 12 month follow up period for any of the main or secondary outcome measures.\n These results do not support the hypothesis that the introduction of an educational package and a written guided self-management plan to the parents of pre-school children with asthma who had recently attended hospital for troublesome asthma or wheeze reduces morbidity over the subsequent 12 months.", "nan", "To examine the effectiveness of an interdisciplinary intervention for pediatric asthma.\n Randomized, controlled study.\n Urban tertiary-referral pediatric hospital.\n One hundred seventy-five patients with asthma lacking written treatment plans and presenting with asthma-related emergency department visits (two or more) and/or hospitalizations (one or more) in the past year were randomized to a comparison group receiving medical care alone (n = 86) or to an interdisciplinary intervention group receiving medical care, asthma education, and problem-solving therapy (n = 89)\n All participants received written asthma management plans, peak flow meters, and spacer devices. The intervention group also received asthma education, an asthma risk profile assessment, brief problem-solving therapy, and access to a 24-h nurse advice line. The primary outcome measure was change in asthma symptoms, and secondary outcomes included health-care utilization and asthma-related quality of life.\n Both groups demonstrated significant reductions in asthma symptoms and improvements in quality of life without any between-group differences identified over the course of follow-up. In contrast, the intervention group demonstrated less frequent health-care utilization than the comparison group, with 28% of the intervention group requiring emergency department or inpatient services for asthma compared to 41% of the comparison group (adjusted odds ratio, 1.92; 95% confidence interval, 1.00 to 3.69) over the 12-month follow-up period.\n This study examined the effectiveness of an interdisciplinary intervention for undertreated asthma. The intervention did not result in improvements in asthma symptoms, but accomplished modest reductions in the utilization of acute medical care." ]

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[ "Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. The Trials of Hypertension Prevention Collaborative Research Group.", "Increasing fruit and vegetable consumption through worksites and families in the treatwell 5-a-day study.", "Effects of the DASH diet alone and in combination with exercise and weight loss on blood pressure and cardiovascular biomarkers in men and women with high blood pressure: the ENCORE study.", "Effects of a multilevel dietary intervention in religious organizations.", "High vegetable and fruit diet intervention in premenopausal women with cervical intraepithelial neoplasia.", "Efficacy of nonpharmacologic interventions in adults with high-normal blood pressure: results from phase 1 of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group.", "Randomised controlled factorial trial of dietary advice for patients with a single high blood pressure reading in primary care.", "Final results of the Maryland WIC 5-A-Day Promotion Program.", "Feasibility of a randomized trial of a low-fat diet for the prevention of breast cancer: dietary compliance in the Women's Health Trial Vanguard Study.", "The impact of the Guidelines for a Healthy Diet of The Netherlands Nutrition Council on total and high density lipoprotein cholesterol in hypercholesterolemic free-living men.", "The effects of a low-fat/high-fiber diet on sex hormone levels and menstrual cycling in premenopausal women: a 12-month randomized trial (the diet and hormone study).", "A randomized controlled trial of a public health nurse directed treatment program for rural patients with high blood cholesterol.", "Long-term effects of a communication intervention for Spanish-dominant Latinas.", "Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group.", "Effects of fruit and vegetable consumption on plasma antioxidant concentrations and blood pressure: a randomised controlled trial.", "Stage-matched nutrition guidance for patients at elevated risk for cardiovascular disease: a randomized intervention study in family practice.", "Psychosocial mediation of fruit and vegetable consumption in the body and soul effectiveness trial.", "Combined diet and exercise intervention reverses the metabolic syndrome in middle-aged males: results from the Oslo Diet and Exercise Study.", "Dietary strategies for lowering homocysteine concentrations.", "Innovative newsletter interventions improve fruit and vegetable consumption in healthy adults.", "Effect of dietary counselling on blood pressure and arterial plasma catecholamines in primary hypertension.", "Cholesterol-lowering effect of the Food for Heart Nutrition Education Program.", "Dietary treatment of patients with mild to moderate hypertension in a general practice: a pilot intervention study (1). The first three months.", "Exploring the feasibility and effects of a high-fruit and -vegetable diet in healthy women.", "Prospective, randomized, controlled comparison of the effects of low-fat and low-fat plus high-fiber diets on serum lipid concentrations.", "Long-term (1- and 2-year) effects of lifestyle intervention in type 2 diabetes relatives.", "Randomized trial testing the effect of peer education at increasing fruit and vegetable intake.", "A randomized controlled trial of a physician-directed treatment program for low-income patients with high blood cholesterol: the Southeast Cholesterol Project.", "Blood pressure change in a free-living population-based dietary modification study in Japan.", "Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.", "Nutrition intervention for high-risk auto workers: results of the Next Step Trial.", "Increasing vegetable and fruit intake: randomized intervention and monitoring in an at-risk population.", "A dietary intervention in primary care practice: the Eating Patterns Study.", "Effects of high fruit-vegetable and/or low-fat intervention on plasma micronutrient levels.", "A randomized trial of a tailored, self-help dietary intervention: the Puget Sound Eating Patterns study.", "Implementation of a 4-y, high-fiber, high-fruit-and-vegetable, low-fat dietary intervention: results of dietary changes in the Polyp Prevention Trial.", "Diet and exercise are equally effective in reducing risk for cardiovascular disease. Results of a randomized controlled study in men with slightly to moderately raised cardiovascular risk factors.", "The Women's Health Trial Feasibility Study in Minority Populations: design and baseline descriptions.", "Randomized controlled trial: effect of nutritional counselling in general practice.", "Preliminary trial of the effect of general practice based nutritional advice.", "One-year results from a brief, computer-assisted intervention to decrease consumption of fat and increase consumption of fruits and vegetables.", "Dietary Counseling for High Blood Cholesterol in Families at Risk of Coronary Disease." ]

[ "To provide a firmer basis for preventing high blood pressure (BP), we tested interventions to promote weight loss, dietary sodium reduction, and their combination for lowering diastolic BP, systolic BP, and the incidence of hypertension during a 3- to 4-year period.\n We conducted a randomized, 2 x 2 factorial, clinical trial, with BP levels measured by blinded observers. Nine academic medical centers recruited 2382 men and women (age range, 30-54 years) not taking antihypertensive drugs, with a diastolic BP of 83 to 89 mm Hg, a systolic BP lower than 140 mm Hg, and a body mass index (the weight in kilograms divided by the square of the height in meters) representing 110% to 165% of desirable body weight. Counseling aimed at helping participants achieve their desirable weight or a 4.5-kg or more weight reduction (in the weight loss and combined groups) and/or sodium intake of 80 mmol/d (in the sodium reduction and combined groups) was provided.\n From baseline, participants' weight decreased by 4.3 to 4.5 kg at 6 months and by approximately 2 kg at 36 months in the weight loss and combined groups compared with weight changes in the usual care group (all groups, P < .001). Sodium excretion decreased 50 and 40 mmol/d at 6 and 36 months, respectively, in the sodium reduction group and about 15 mmol/d less at each time point in the combined group compared with the usual care group (all groups, P < .01). Compared with the usual care group, BP decreased 3.7/2.7 mm Hg in the weight loss group, 2.9/1.6 mm Hg in the sodium reduction group, and 4.0/2.8 mm Hg in the combined group at 6 months (all groups, P < .001). At 36 months, BP decreases remained greater in the active intervention groups than in the usual care group (weight loss group, 1.3/0.9 mm Hg; sodium reduction group, 1.2/0.7 mm Hg; combined group, 1.1/0.6 mm Hg). Differences were statistically significant for systolic and diastolic BP in the weight loss group and for systolic BP in the sodium reduction group. Through 48 months, the incidence of hypertension (BP > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic or the use of antihypertensive drugs) was significantly less in each active intervention group than the usual care group (average relative risks, 0.78-0.82).\n In overweight adults with high-normal BP, weight loss and reduction in sodium intake, individually and in combination, were effective in lowering systolic and diastolic BP, especially in the short-term (6 months). Although the effects on average BP declined over time, reductions in hypertension incidence were achieved.", "We report on the results of the Treatwell 5-a-Day study, a worksite intervention aimed at increasing consumption of fruits and vegetables.\n Twenty-two worksites were randomly assigned to 3 groups: (1) a minimal intervention control group, (2) a worksite intervention, and (3) a worksite-plus-family intervention. The interventions used community-organizing strategies and were structured to target multiple levels of influence, following a socioecological model. Data were collected by self-administered employee surveys before and after the intervention; the response rate was 87% (n = 1359) at baseline and 76% (n = 1306) at follow-up. A process tracking system was used to document intervention delivery.\n After control for worksite, gender, education, occupation, race/ethnicity, and living situation, total fruit and vegetable intake increased by 19% in the worksite-plus-family group, 7% in the worksite intervention group and 0% in the control group (P = .05). These changes reflect a one half serving increase among workers in the worksite-plus-family group compared with the control group (P = .018).\n The worksite-plus-family intervention was more successful in increasing fruit and vegetable consumption than was the worksite intervention. Worksite interventions involving family members appear to be a promising strategy for influencing workers' dietary habits.", "Although the DASH (Dietary Approaches to Stop Hypertension) diet has been shown to lower blood pressure (BP) in short-term feeding studies, it has not been shown to lower BP among free-living individuals, nor has it been shown to alter cardiovascular biomarkers of risk.\n To compare the DASH diet alone or combined with a weight management program with usual diet controls among participants with prehypertension or stage 1 hypertension (systolic BP, 130-159 mm Hg; or diastolic BP, 85-99 mm Hg).\n Randomized, controlled trial in a tertiary care medical center with assessments at baseline and 4 months. Enrollment began October 29, 2003, and ended July 28, 2008.\n Overweight or obese, unmedicated outpatients with high BP (N = 144).\n Usual diet controls, DASH diet alone, and DASH diet plus weight management.\n The main outcome measure is BP measured in the clinic and by ambulatory BP monitoring. Secondary outcomes included pulse wave velocity, flow-mediated dilation of the brachial artery, baroreflex sensitivity, and left ventricular mass.\n Clinic-measured BP was reduced by 16.1/9.9 mm Hg (DASH plus weight management); 11.2/7.5 mm (DASH alone); and 3.4/3.8 mm (usual diet controls) (P < .001). A similar pattern was observed for ambulatory BP (P < .05). Greater improvement was noted for DASH plus weight management compared with DASH alone for pulse wave velocity, baroreflex sensitivity, and left ventricular mass (all P < .05).\n For overweight or obese persons with above-normal BP, the addition of exercise and weight loss to the DASH diet resulted in even larger BP reductions, greater improvements in vascular and autonomic function, and reduced left ventricular mass.\n clinicaltrials.gov Identifier: NCT00571844.", "This study examined how to improve dietary habits of individuals from the general public.\n The Eating for a Healthy Life project was a randomized trial.\n The study was conducted among members of religious organizations (ROs).\n Participants were a sample of RO members.\n The intervention was a multilevel package, based on our previous experience, designed to lower fat and increase fruit and vegetable consumption.\n The Eating Behaviors Questionnaire was administered preintervention and postintervention, together with 24-hour food recalls in a randomly selected subset. Analysis. Linear mixed models were used to evaluate the study's intervention, incorporating the design effects of blocking, intraclass correlation within RO, and correlation between the preintervention and postintervention points.\n Participants (n = 2175) reported significantly healthier dietary behaviors in intervention ROs at the 12-month follow-up period, compared to participants in the comparison ROs, for a fat scale change of .08 summary scale points and an adjusted intervention effect of .06 overall.\n Dietary intervention through ROs is a positive and successful method of changing dietary habits.", "To examine whether diet intervention can promote increased vegetable and fruit intake, as reflected in increased plasma carotenoid and decreased plasma total homocysteine concentrations, in premenopausal women with cervical intraepithelial neoplasia, a precancerous condition.\n Randomized controlled diet intervention study.\n Fifty-three free-living premenopausal women who had been diagnosed with cervical intraepithelial neoplasia, were randomly assigned to an intervention (n = 27) or a control (n = 26) group.\n Individualized dietary counseling to increase vegetable and fruit intake.\n Diet was assessed by food frequency questionnaire. Plasma carotenoids and total homocysteine were measured at enrollment and at 6 months follow up.\n Associations between baseline plasma concentrations of carotenoids and homocysteine and influencing factors were examined with multiple regression analysis. Repeated measures analysis of variance was used to test for group by time effects in these plasma concentrations. Plasma carotenoids at baseline and 6 months in the study groups, and differences in homocysteine concentrations from baseline to 6 months, were compared with independent sample t tests.\n Repeated measures analysis of variance showed significant group by time effects (P<.01) in plasma carotenoid and homocysteine concentrations. In the intervention group, total plasma carotenoids increased by an average of 91%, from 2.04+/-0.13 (mean+/-standard error of the mean) to 3.90+/-0.56 micromol/L and plasma total homocysteine was reduced by 11%, from 9.01+/-0.40 to 8.10+/-0.44 micromol/L (P<.003). Neither changed significantly in the control group.\n Individualized dietary counseling can effectively promote increased vegetable and fruit intake in premenopausal women. This dietary pattern may reduce risk for cancer and other chronic diseases and also promote an improvement in folate status.", "Phase 1 of the Trials of Hypertension Prevention was conducted in 2182 adults, aged 35-54 y, with diastolic blood pressure of 80-89 mm Hg to test the feasibility and blood pressure-lowering effects of seven nonpharmacologic interventions (weight loss, sodium reduction, stress management, and supplementation with calcium, magnesium, potassium, and fish oil). At 6 and 18 mo, weight loss and sodium reduction were well-tolerated and produced significant declines in systolic and diastolic blood pressures (-2.9/-2.4 and -2.1/-1.2 mm Hg for weight loss and sodium reduction, respectively, at 18 mo). None of the other interventions lowered blood pressure significantly at either the 6- or 18-mo follow-up visits. These results suggest that both weight loss and sodium reduction provide an effective means to prevent hypertension. The long-term effects of both of these interventions are being tested in phase 2 of the trial.", "To assess the effect of brief interventions during the \"watchful waiting\" period for hypertension.\n Factorial trial.\n General practice.\n 296 patients with blood pressure > 160/90 mm Hg were randomised to eight groups defined by three factors: an information booklet; low sodium, high potassium salt; prompt sheets for high fruit, vegetable, fibre; and low fat.\n Blood pressure (primary outcome); secondary outcomes of diet, weight, and dietary biomarkers (urinary sodium:potassium (Na:K) ratio; carotenoid concentrations).\n Blood pressure was not affected by the booklet (mean difference (diastolic blood pressure) at one month 0.2, 95% confidence interval 1.6 to 2.0), salt (0.13; 1.7 to 2.0), or prompts (0.52; 1.3 to 2.4). The salt decreased Na:K ratio (difference 0.32; 0.08 to 0.56, P = 0.01), and the prompts helped control weight (difference 0.39 (0.85 to 0.05) kg at one month, P = 0.085; 1.2 (0.1 to 2.25) kg at six months, P = 0.03). Among those with lower fruit and vegetable consumption (< 300 g per day), prompts increased fruit and vegetable consumption and also carotenoid concentrations (difference 143 (16 to 269) mmol/l, P < 0.03) but did not decrease blood pressure.\n During watchful waiting, over and above the effect of brief advice and monitoring, an information booklet, lifestyle prompts, and low sodium salt do not reduce blood pressure. Secondary analysis suggests that brief interventions-particularly lifestyle prompts-can make useful changes in diet and help control weight, which previous research indicates are likely to reduce the long term risk of stroke.", "This National Cancer Institute-funded study sought to increase fruit and vegetable consumption among women served by the WIC program in Maryland.\n Over a 2-year period, a multifaceted intervention program using a randomized crossover design sought to increase fruit and vegetable consumption at 16 WIC program sites in Baltimore City and 6 Maryland counties. Participants were surveyed at baseline, 2 months postintervention, and 1 year later.\n Two months postintervention, mean daily consumption had increased by 0.56 +/- 0.11 servings in intervention participants and 0.13 +/- 0.07 servings in control participants (P = .002). Intervention participants also showed greater changes in stages of change, knowledge, attitudes, and self-efficacy. Changes in consumption were closely related to number of nutrition sessions attended, baseline stage of change, race, and education. One year later, mean consumption had increased by an additional 0.27 servings in both intervention and control participants.\n Dietary changes to prevent cancer can be achieved and sustained in this hard-to-reach, low-income population. However, many obstacles must be overcome to achieve such changes.", "The Women's Health Trial Vanguard Study was conducted to examine the feasibility of a nationwide, randomized multicenter intervention trial to test the hypothesis that a low-fat diet followed for a period of 10 years will reduce breast cancer risk. Women ages 45-69 years at increased risk of breast cancer were randomized into intervention (low-fat diet, n = 184) and control (usual diet, n = 119) groups. On the basis of 4-day food records, baseline fat intakes were comparable in the two groups, averaging 1,718 kcal with 39% of energy as fat. Intervention women reported substantially lower fat intake at 6 (20.9% kcal), 12 (21.6%), and 24 months (22.6% kcal). In contrast, control women reported only slight reductions in fat intake (37.3% kcal at 12 months and 36.8% kcal at 24 months). Evidence that these women were indeed complying with the low-fat dietary intervention comes from (a) the reasonable nature of reported nutrient changes within food groups in the intervention women and (b) agreement between observed and expected differences in plasma total cholesterol between the control and the intervention groups. At 12 months, the observed control - intervention plasma cholesterol difference was 13.1 +/- 4.6 mg/dl while the expected difference based on the Keys equation was 15.1 +/- 1.1 mg/dl; at 24 months, the observed difference was 15.5 +/- 4.3 mg/dl and the expected difference was 12.0 +/- 1.2 mg/dl. These analyses indicate that the intervention women made substantial dietary changes and have successfully maintained these changes over a 2-year period. This study thus demonstrates the feasibility of a randomized trial with an intensive low-fat dietary intervention.", "To study the impact of dietary intervention on the plasma total and high density lipoprotein cholesterol (HDL cholesterol) levels in hypercholesterolemic men, the authors selected 80 male participants in a monitoring risk factor project carried out in Amsterdam, The Netherlands. These men had plasma total cholesterol levels of between 6.5 and 10.0 mmol/liter (between 251 and 387 mg/dl) and were randomly assigned to either the intervention (n = 39) or the control (n = 41) group. At the start of the intervention period, after 5 weeks, and after 26 weeks, both the intervention and the control groups were examined. This examination consisted of a measurement of height, weight, plasma total and HDL cholesterol, and a dietary interview. The intervention program consisted of a personalized dietary advice to the respondent, based on the report of the Netherlands Nutrition Council. The study took place between September 1987 and November 1988. Because of this intervention program, the plasma total and HDL cholesterol levels decreased. The difference in change in plasma total cholesterol between the intervention and control groups was 0.47 mmol/liter (18 mg/dl) after 5 weeks and 0.30 mmol/liter (12 mg/dl) after 26 weeks. For HDL cholesterol, a significant difference in change after 5 weeks disappeared after 26 weeks. The public health implications of the decrease in plasma total cholesterol are discussed.", "Reduction of cumulative exposure to endogenous ovarian steroid hormones is a postulated method for reducing the risk of carcinoma of the breast and other malignancies. Although there are data from trials evaluating the effect of low-fat and high-fiber diets on sex hormone levels in premenopausal women, to the authors' knowledge none of these trials has combined a relatively large number of participants, follow-up of > 2-3 months, parallel controls receiving a usual diet, and careful timing of blood sampling within the menstrual cycle.\n A total of 213 healthy women, ages 20-40 years, were randomly assigned to follow their usual diet or to adopt an isocaloric diet with goals of 20% calories as fat, total fiber of 25 g/day, and at least 8 fruit or vegetable servings per day. Serum levels of total estradiol (E2), sex hormone-binding globulin (SHBG), non-SHBG-bound estradiol (NSBE2), SHBG, and progesterone were evaluated during a menstrual cycle at baseline, and at 4 cycles (C4) and 12 cycles (C12) after the start of the intervention. Serum was collected during each test cycle 7-9 days after the detection of an luteinizing hormone peak in the urine. One hundred eighty-nine women provided serum at C4 and 176 women at C12.\n Serum E2 decreased by an average of 7.5% or 7.8 pg/mL (95% confidence interval [95% CI], -16.0-0.04) at C12 in the intervention group, versus a decrease of 0.9% or 0.9 pg/mL (95% CI, -9.5-7.7) in the control group (the P value for the difference between the treatment groups was 0.25). Results for NSBE2 were very similar to those for total estradiol. There were no material effects found to result from intervention with regard to SHBG or progesterone. The results did not differ by baseline age, body mass index, or baseline hormone level above or below the median, and were not likely to be affected by weight change, which amounted to a mean loss of only 0.23 kg in the diet group versus a gain of 0.17 kg in the control group. The decrease in serum E2 associated with intervention was not greater when subjects were stratified by self-reported adherence to the dietary goals.\n The results of the current study suggest that the effects of this isocaloric low-fat, high-fiber diet pattern on circulating ovarian steroids were modest or nonexistent. However, the observed 7.5% reduction in estradiol could have biologic significance if it persisted over many years. Moreover, underestimation of the true dietary effect could have occurred because of incomplete adherence to assigned diets. Weight loss and weight control through midlife could be a more effective and feasible approach to dietary intervention in reducing the risk of breast carcinoma.\n Copyright 2003 American Cancer Society.", "Many rural residents do not have access to high-quality nutrition counseling for high blood cholesterol. The objective of this study was to assess the effectiveness of an intervention program designed to facilitate dietary counseling for hypercholesterolemia by rural public health nurses.\n Eight health departments (216 participants) were randomized to give the special intervention (SI) and nine (252 participants) to give the minimal intervention (MI). The SI consisted of three individual diet counseling sessions given by a public health nurse, using a structured dietary intervention (Food for Heart Program), referral to a nutritionist if lipid goals were not achieved at 3-month follow-up, and a reinforcement phone call and newsletters. Diet was assessed by the Dietary Risk Assessment (DRA), a validated food frequency questionnaire, at baseline, 3-, and 12-month follow-up; blood lipids and weight were assessed at baseline, 3-, 6-, and 12-month follow-up.\n Participants were largely female (71%), older (mean age 55), and white (80%). At 3-month follow-up, the average reduction (indicating dietary improvement) in total Dietary Risk Assessment score was 3.7 units greater in the SI group (95% confidence interval [CI] 1.9 to 5.5, P = 0.0006), while both groups experienced a similar reduction in blood cholesterol, 14.1 mg/dL (0.37 mmol/L) for SI and 14.5 mg/dL (0.38 mmol/L) for minimal intervention group (difference -0.4 mg/dL [-0.010 mmol/L], 95% CI -12.5 to 11.7 [-0.32 to 0.30], P = 0.9). At 12-month follow-up, the reduction in total Dietary Risk Assessment score was 2.1 units greater in the SI group (95% CI 0.8 to 3.5, P = 0.005), while the reduction in blood cholesterol was similar in both groups, 18.4 mg/dL (0.48 mmol/L) for SI and 15.6 mg/dL (0.40 mmol/L) for minimal intervention group (difference 2.8 mg/dL [0.07 mmol/L], 95% CI -7.5 to 13.1 [-0.19 to 0.34], P = 0.6). During follow-up, weight loss was greater in the SI group; the difference between groups was statistically significant at 3 (1.9 lb [0.86 kg], 95% CI 0.3 to 3.4 [0.14 to 1.55], P = 0.022) and 6 months (2.1 lb [0.95 kg], 95% CI 0.1 to 4.1 [0.04 to 1.86], P = 0.04). At 12 months, the difference was not significant (1.6 lb [0.73 kg], 95% CI -0.05 to 3.7 [-0.02 to 1.68], P = 0.13).\n Improvement in self-reported dietary intake was significantly greater in the SI group, while reduction in blood cholesterol was similar in both groups.", "Few studies compare the influence of different types of dietary interventions on the dietary practices of Latinas in the short and long term. The present study examined the 1-year impact of two innovative behavior-change approaches to reduce dietary fat and increase fiber.\n Three-group randomized controlled trial: (1) personalized dietary counseling via lay heath advisors (promotoras) plus tailored print materials delivered via the mail, (2) tailored mailed print materials only, and (3) targeted mailed \"off-the-shelf\" materials.\n A total of 357 Latinas were randomly assigned to the three aforementioned conditions.\n Promotora and tailored print materials.\n Fat intake (total grams of fat and percent calories from dietary fat) and number of grams of dietary fiber.\n Earlier work reported that at immediate post-intervention the promotora group achieved significantly lower levels of total fat grams, and lower levels of energy intake, total saturated fat, total carbohydrates, glucose, and fructose than the targeted group. However, the present longitudinal analyses suggest that the effects achieved by the promotoras dissipated over the 12-month follow-up period while the effects of the tailored group concurrently improved.\n The high interactivity (i.e., calls, visits) of the promotora condition may have been the most salient reinforcer and may have led to further tailoring, making this type of intervention more effective than the comparison groups in the short term. Further research should explore whether booster sessions involving promotoras help to maintain the impact over time.", "We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers.\n We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups: an intervention group given intensive counseling and assigned to follow a diet that was low in fat (20 percent of total calories) and high in fiber (18 g of dietary fiber per 1000 kcal) and fruits and vegetables (3.5 servings per 1000 kcal), and a control group given a standard brochure on healthy eating and assigned to follow their usual diet. Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps; they remained in the study for approximately four years, undergoing colonoscopy one and four years after randomization.\n A total of 1905 of the randomized subjects (91.6 percent) completed the study. Of the 958 subjects in the intervention group and the 947 in the control group who completed the study, 39.7 percent and 39.5 percent, respectively, had at least one recurrent adenoma; the unadjusted risk ratio was 1.00 (95 percent confidence interval, 0.90 to 1.12). Among subjects with recurrent adenomas, the mean (+/-SE) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group. The rate of recurrence of large adenomas (with a maximal diameter of at least 1 cm) and advanced adenomas (defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high-grade dysplasia, including carcinoma) did not differ significantly between the two groups.\n Adopting a diet that is low in fat and high in fiber, fruits, and vegetables does not influence the risk of recurrence of colorectal adenomas.", "High dietary intakes of fruit and vegetables are associated with reduced risks of cancer and cardiovascular disease. Short-term intensive dietary interventions in selected populations increase fruit and vegetable intake, raise plasma antioxidant concentrations, and lower blood pressure, but long-term effects of interventions in the general population are not certain. We assessed the effect of an intervention to increase fruit and vegetable consumption on plasma concentrations of antioxidant vitamins, daily fruit and vegetable intake, and blood pressure.\n We undertook a 6-month, randomised, controlled trial of a brief negotiation method to encourage an increase in consumption of fruit and vegetables to at least five daily portions. We included 690 healthy participants aged 25-64 years recruited from a primary-care health centre.\n Plasma concentrations of alpha-carotene, beta-carotene, lutein, beta-cryptoxanthin, and ascorbic acid increased by more in the intervention group than in controls (significance of between-group differences ranged from p=0.032 to 0.0002). Groups did not differ for changes in lycopene, retinol, alpha-tocopherol, gamma-tocopherol, or total cholesterol concentrations. Self-reported fruit and vegetable intake increased by a mean 1.4 (SD 1.7) portions in the intervention group and by 0.1 (1.3) portion in the control group (between-group difference=1.4, 95% CI 1.2-1.6; p<0.0001). Systolic blood pressure fell more in the intervention group than in controls (difference=4.0 mm Hg, 2.0-6.0; p<0.0001), as did diastolic blood pressure (1.5 mm Hg, 0.2-2.7; p=0.02).\n The effects of the intervention on fruit and vegetable consumption, plasma antioxidants, and blood pressure would be expected to reduce cardiovascular disease in the general population.", "To examine stage-matched nutrition counseling by family physicians and its effect on dietary intake, anthropometry, and serum lipid levels in patients at elevated risk for cardiovascular disease.\n In this controlled trial, patients randomized to intervention practices received nutrition information following the Stages-of-Change Model, and patients randomized to control practices received usual care.\n At both 6 and 12 months after baseline, total fat intake and saturated fat intake declined significantly more in the intervention group than in the control group: -5.7% and -2.6% of energy, respectively, at 6 months, and -3.6% and -1.7% of energy, respectively, at 12 months. For energy intake, body weight, and BMI, there were significant differences between groups only at 6 months: -0.8 megajoules (MJ), -0.7 kg, and -0.3 kg/m(2), respectively. None of the serum lipid values changed significantly between groups at 12 months.\n Nutritional counseling based on stages of change led to reductions in dietary fat intake and weight loss in the short term. However, we found no corresponding changes in serum lipid concentrations.", "In this study the authors examined psychosocial variables as mediators for fruit and vegetable (FV) intake in a clustered, randomized effectiveness trial conducted in African American churches. The study sample included 14 churches (8 intervention and 6 control) with 470 participants from the intervention churches and 285 participants from the control churches. The outcome of FV intake and the proposed mediators were measured at baseline and at 6-month follow-up. Structural equation modeling indicated that the intervention had direct effects on social support, self-efficacy, and autonomous motivation; these variables also had direct effects on FV intake. Applying the M. E. Sobel (1982) formula to test significant mediated effects, the authors confirmed that social support and self-efficacy were significant mediators but that autonomous motivation was not. Social support and self-efficacy partially mediated 20.9% of the total effect of the intervention on changes in FV intake. The results support the use of strategies to increase social support and self-efficacy in dietary intervention programs.", "We examined the single and combined effects of a 1-year diet and exercise intervention on the International Diabetes Federation (IDF) metabolic syndrome among middle-aged males. The study was a randomized, controlled, 2 x 2 factorial intervention study. Participants included 137 men with metabolic syndrome according to the IDF criteria aged 40-49 years randomly allocated to four intervention groups: diet alone (n=34), exercise alone (n=34), the combination of the diet and exercise intervention (n=43) or control (n=26). The main outcome measure was metabolic syndrome as defined by IDF criteria (2005). In the combined diet and exercise group, 14 participants (32.6%) (P<0.0001 as compared with control) had the metabolic syndrome after 1-year intervention. In the diet-only group, 22 participants (64.7%) (P=0.023 vs control) and in the exercise-only group 26 participants (76.5%) (P=0.23 vs control) had the metabolic syndrome following the intervention. Utilizing the factorial design, both dietary and exercise intervention had significant effects (P<0.005) on the resolution of the metabolic syndrome. Both exercise and dietary intervention reduced metabolic syndrome prevalence compared with control after 1 year of intervention. However, the combined diet and exercise intervention was significantly more effective than diet or exercise alone in the treatment of the metabolic syndrome.", "Elevated plasma total homocysteine (tHcy) concentrations are associated with increased risk of vascular disease, and there is a strong inverse association between dietary and blood folate and blood tHcy concentrations. Increased folate consumption may lower the risk of tHcy-mediated cardiovascular disease.\n The objective was to determine the most appropriate means of increasing dietary folate to reduce plasma tHcy.\n Sixty-five free-living subjects aged 36-71 y with tHcy concentrations >/=9 micromol/L participated in a randomized, controlled trial to compare 3 approaches for increasing dietary folate to approximately 600 microg/d: folic acid supplementation, consumption of folic acid-fortified breakfast cereals, and increased consumption of folate-rich foods.\n An intake of 437 microg folic acid/d from supplements resulted in a 27-nmol/L increase in serum folate and a 21% reduction in tHcy, relative to the change in a control group. In subjects who consumed folic acid-fortified breakfast cereal, folate intake increased by an average of 298 microg, serum folate increased by 21 nmol/L, and tHcy concentrations decreased by 24%. Increased intakes of folate-rich foods resulted in a 418-microg increase in dietary folate, a 7-nmol/L increase in serum folate, and a 9% reduction in tHcy concentrations. The decrease in tHcy was negatively correlated (r = -0.66) with the increase in serum folate.\n Daily consumption of folic acid-fortified breakfast cereals and the use of folic acid supplements appear to be the most effective means of reducing tHcy concentrations. The reduction in tHcy was significantly negatively correlated with the increase in serum folate, which may be a useful marker for measuring dietary change.", "To evaluate the effectiveness of computer-tailored newsletter interventions in improving the number and variety of fruits and vegetables eaten by adults.\n The 4-group randomized trial with pre- and postintervention measures consisted of a control group and 3 intervention groups receiving nontailored newsletters, computer-tailored newsletters, or tailored newsletters with tailored goal-setting information. Intervention groups received 1 newsletter each month for 4 months.\n Baseline surveys were completed by 710 health maintenance organization clients. Postintervention surveys administered 6 months after baseline were completed by 573 participants (80.8%).\n All newsletters contained strategies for improving fruit and vegetable consumption. Tailored newsletters used computer algorithms to match a person's baseline survey information with the most relevant newsletter messages for promoting dietary change.\n Daily intake and weekly variety of fruits and vegetables were measured using a food frequency questionnaire.\n Analysis of covariance and Tukey's honestly significant difference test were used to assess differences in the number and variety of fruits and vegetables consumed among intervention groups.\n For persons completing postintervention surveys (n = 573), all 3 newsletter groups had significantly higher daily intake and variety scores compared with the control group. Although there was a trend of improved intake and variety with each added newsletter element, there were no significant differences at follow-up among the newsletter groups.\n Newsletters can be effective in improving the fruit and vegetable consumption of adults. In this study, a computer-tailoring system did not significantly enhance the effect of the nutrition newsletters on fruit and vegetable intake.", "There is still a need of support for nonpharmacologic treatment of uncomplicated, mild-to-moderate essential hypertension. We investigated whether a low sodium-based diet implemented by a nutritionist could lower blood pressure and affect sympathetic activity. Middle-aged, otherwise healthy men with never-treated essential hypertension (n = 95) were randomized to an intervention group, a blood pressure control group, and a time control group. The intervention group was advised to use less sodium chloride in their diet, and if necessary, less saturated fat and decrease body weight. They attended regular clinic visits as did the blood pressure control group. After 1 year, the intervention group had achieved on average 72 mmol/24 h lower urinary sodium excretion (P < .001) and a decrease in body weight of 2.7 +/- 0.5 kg (P < .001). Both supine and standing mean blood pressure were on average 8 to 10 mm Hg lower after intervention compared with the two control groups (P < .001). Arterial plasma epinephrine, measured in all 40-year-old subjects (n = 30), decreased in parallel in all three groups (P < .05), indicating some habituation to the invasive procedure and clinic visits. However, the decrease in norepinephrine was significant (P < .001) only in the intervention group; it correlated with the weight loss (r = 0.76, P < .05) and was significantly higher (P < .05) than in both control groups. These results suggest that broad dietary advice (ie, low intake of sodium chloride, saturated fat and energy), implemented by a nutritionist, may have a significant blood pressure lowering effect and a favorable sympathicolytic effect in uncomplicated, mild-to-moderate essential hypertension.", "The objective of this prospective, randomized controlled trial was to assess the effectiveness of the Food For Heart Program patient nutrition tool in hypercholesterolemic outpatients. The setting for this study was an urban academic primary-care practice; 175 hypercholesterolemic adults not taking cholesterol-lowering medications were enrolled as subjects. The study intervention involved four monthly dietary counseling visits, using the Food For Heart Program, conducted by the study research assistant. The main outcome measures were fasting serum lipids (primary); body weight (secondary); and change in Dietary Risk Assessment score (intervention group only), analyzed using Student's t test. Our results showed that total and low-density lipoprotein cholesterol decreased 0.40+/-0.65 mmol/L and 0.32+/-0.58 mmol/L, respectively, in the intervention group (n=91), compared with 0.06+/-0.57 mmol/L and 0.0088+/-0.56 mmol/L in the control group (n=84) ( P <.001). There was no significant change in high-density lipoprotein cholesterol. Intervention subjects lost a small but statistically significant amount of weight, 2.2+/-7.4 pounds ( P <.01), and decreased their Dietary Risk Assessment score 5.9+/-6.5 points ( P <.001). Based on these findings, we concluded that total and low-density lipoprotein cholesterol, weight, and dietary risk for coronary heart disease decreased significantly in hypercholesterolemic patients counseled using the Food For Heart Program.", "Thirty-five patients with mild to moderate hypertension were randomised into a three months' dietary advised and a three months' control group. The diet was of a composition currently considered to be appropriate, and was monitored by a dietitian. Statistically significant decreases in diastolic blood pressure, mean arterial pressure, sodium excretion, and low density lipoprotein (LDL)-cholesterol occurred in the intervention group, although differences in change between the intervention and the control group were, except for LDL-cholesterol, not statistically significant. Thus, it did not become clear whether and to what extent change in diet was responsible for the lowering of the blood pressure in the intervention group.", "Based on reports that fruits and vegetables may protect against breast cancer, this randomized intervention study tested the feasibility of increasing fruit and vegetable intake among healthy women to 9 daily servings through individual dietary counseling and group activities. Adherence to the dietary recommendations was monitored by 24-h food recalls, log sheets, and plasma carotenoid assessments. To explore possible cancer protective mechanisms of fruits and vegetables, we investigated the treatment effect on plasma phenol levels and on thiobarbituric acid-reactive substances measured as malondialdehyde equivalents, a possible marker of oxidative damage. At baseline, women in the intervention (n = 13) and control (n = 16) group reported an average daily consumption of 3.3 and 3.2 fruit and vegetable servings, respectively. After 3 and 6 months of intervention, intake in the intervention group had increased to 8.3 and 7.4 servings, whereas the control group reported an average of 4.2 and 4.1 daily servings. An increase of plasma carotenoid levels from 1249 microg/liter at baseline to 1854 and 1827 microg/liter after 3 and 6 months confirmed compliance with the dietary recommendations in the intervention group. Plasma carotenoid levels among controls changed slightly from 1165 to 1231 and 1291 microg/liter Whereas total phenol levels did not respond according to our hypothesis, malondialdehyde levels decreased slightly in the intervention group. These results suggest that motivated women can substantially increase their fruit and vegetable intake, which leads to a notable increase in plasma carotenoid levels.", "Previous studies examining the hypocholesterolemic effects of high-soluble-fiber diets have not been designed to control for dietary fat intake. Serum cholesterol reductions may therefore be accounted for by differences in consumption of fat. Moderately hypercholesterolemic, nonobese, Caucasian men and women, 30-50 y old were randomly assigned to low-fat, low-fat plus high-fiber, or usual-diet groups and followed for 12 mo. At 12 mo the high-fiber group consumed significantly more soluble fiber than both the low-fat and usual-diet groups (P = 0.0063 and P = 0.0001); the high-fiber group did not differ from the low-fat group in quantity of dietary fat consumed. The high-fiber group experienced a greater average reduction (13%) in serum cholesterol than did the low-fat (9%) and usual-diet (7%) groups. After adjustment for relevant covariates, the reduction in the high-fiber group was significantly greater than that in the low-fat group (P = 0.0482). Supplementation with soluble fiber reduces serum cholesterol beyond the reduction observed with low-fat diet alone.", "To study the long-term (1- and 2-year) effect of a lifestyle intervention on non-diabetic first-degree relatives of type 2 diabetic patients, i.e., the 1-year effect of diet versus diet and exercise in relation to a control group and the 2-year sustainability of these treatment effects.\n Seventy-seven healthy first-degree relatives (men and women) between the ages of 25 and 55 were allocated to one of three groups: diet group (D), diet and exercise group (DE) and control group (C). For ethical reasons, after 1 year the control group began the intervention and were followed for another 2 years. Diet and physical activity counselling was based on current nutrition recommendations, including increased intake of fatty fish and low glycaemic index foods. The fatty acid composition of the erythrocyte membrane was studied as an objective measure of dietary change. Assessments included fasting insulin, 2-h insulin, oral glucose tolerance test (OGTT), anthropometry and blood lipid measurements. Groups D and DE received intensive follow-up through unannounced telephone interviews during the first 4 months.\n Dietary changes were significant at 1 year, and to a large degree sustained at 2 years. Adherence to advice regarding fat quality was confirmed through changes in the fatty acid composition of the erythrocyte membrane. The least active subjects in DE increased their physical activity (PA). At 1 year, group D showed a reduction in the ratio of LDL to HDL cholesterol (p=0.028) while group DE decreased their body weight by 2.7% (p<0.029) and increased HDL (p<0.037) versus controls. At 2 years, cholesterol levels (total, LDL and the ratio LDL/HDL) were reduced within group D and when compared to DE (p=0.022, 0.009, 0.035, respectively). Fasting insulin was reduced within group DE and when compared to group D (p=0.025).\n Positive changes in lifestyle, blood lipids and fasting insulin can be achieved and maintained in a non-diabetic population at risk of type 2 diabetes after 2 years.", "The National Cancer Institute recommends that Americans eat at least five daily servings of fruits and vegetables. National strategies to increase consumption may not reach minority and lower socioeconomic populations. In a randomized trial, peer education was tested for effectiveness at increasing fruit and vegetable intake among lower socioeconomic, multicultural labor and trades employees.\n Employees (n = 2091) completed a baseline survey and received an 18-month intervention program through standard communication channels (e.g., workplace mail, cafeteria promotions, and speakers). Ninety-three social networks (cliques) of employees were identified, which were pair matched on intake. At an interim survey (during months 8 and 9), 11 cliques no longer existed and 41 matched pairs of cliques containing 905 employees remained, with one clique per pair being randomly assigned to the peer education intervention. Employees who were central in the communication flow of the peer intervention cliques served as peer educators during the last 9 months of the intervention program. Fruit and vegetable intake was measured with 24-hour intake recall and with food-frequency questions in baseline, outcome (i.e., at 18 months), and 6-month follow-up surveys. All P values are two-sided.\n By use of multiple regression, statistically significant overall effects of the peer education program were seen in the intake recall (increase of 0.77 total daily servings; P<.0001) and the food-frequency (increase of 0.46 total daily servings; P =.002) questions at the outcome survey. The effect on the total number of servings persisted at the 6-month follow-up survey when measured by the intake recall (increase of 0.41 total daily servings; P =.034) but not the food-frequency (decrease of 0.04 total daily servings; P =.743) questions.\n Peer education appears to be an effective means of achieving an increase in fruit and vegetable intake among lower socioeconomic, multicultural adult employees.", "To assess the effectiveness of a cholesterol-lowering intervention designed to facilitate the management of hypercholesterolemia by primary care clinicians.\n Randomized controlled trial, with randomization of clinician-patient groups.\n Twenty-one community and rural health centers in North Carolina and Virginia.\n Primary care clinicians (n = 42, 71% physicians) and the patients they enrolled with high cholesterol (n = 372). Twenty-two clinicians were randomized to give the special intervention (184 patients) and 20 to give usual care (188 patients). Two thirds of participating patients were women, 40% were African American, and 11% were Native American.\n A 90-minute tutorial to train clinicians how to use a structured assessment and treatment program (Food for Heart Program) consisting of a brief dietary assessment and three 5- to 10-minute dietary counseling sessions given by the primary care clinician, referral to a local dietitian if the low-density lipoprotein cholesterol (LDL-C) remained elevated at 4-month follow-up, and a prompt for the clinician to consider lipid-lowering medication based on the LDL-C at 7-month follow-up.\n Changes in total and LDL cholesterol at 4-month follow-up and averaged over a 1-year follow-up period (4-, 7-, and 12-month follow-up).\n At 4-month follow-up, total cholesterol decreased 0.33 mmol/L (12.6 mg/dL) in the intervention group and 0.21 mmol/L (8.3 mg/dL) in the control group: the difference was 0.11 mmol/L (4.2 mg/dL) (90% confidence interval [CI], -0.02 to 0.24 mmol/L [-0.7 to 9.1 mg/dL]). The average reduction during the 1-year follow-up period was 0.09 mmol/L (3.6 mg/dL) greater in the intervention group (90% CI, -0.01 to 0.19 mmol/L [-0.3 to 7.5 mg/dL]). Eight percent of intervention patients were taking lipid-lowering medication at follow-up visits compared with 15% of control patients. In a subgroup analysis restricted to the 89% of returnees who were not taking lipid-lowering medication, the reduction in total cholesterol at 4-month follow-up was 0.14 mmol/L (5.5 mg/dL) greater in the intervention group (95% CI, 0.01 to 0.28 mmol/L [0.3 to 10.7 mg/dL]); averaged over 1 year, it was 0.14 mmol/L (5.3 mg/dL) greater (95% CI, 0.03 to 0.24 mmol/L [1.2 to 9.4 mg/dL]). Changes in LDL-C were similar.\n Total cholesterol and LDL-C decreased more in the intervention group than in the control group. Overall, the difference in lipid reduction between groups was modest and of borderline statistical significance; among participants who did not take lipid-lowering medication during follow-up, the difference in lipid reduction between groups was larger. We conclude that primary care clinicians can be trained to give a cholesterol-lowering intervention to low-income patients that results in modest, short-term reductions in total cholesterol and LDL-C.", "To assess whether dietary intervention in free-living healthy subjects is effective in improving blood pressure levels.\n Open randomised, controlled trial.\n Free-living healthy subjects in two rural villages in north-eastern Japan.\n Five hundred and fifty healthy volunteers aged 40-69 years.\n Tailored dietary education to encourage a decrease in sodium intake and an increase in the intake of vitamin C and carotene, and of fruit and vegetables.\n Blood pressure, dietary intake and urinary excretion of sodium, dietary carotene and vitamin C, and fruit and vegetable intake data were collected at 1 year after the start of the intervention.\n During the first year, changes differed significantly between the intervention and control groups for dietary (P = 0.002) and urinary excretion (P < 0.001) of sodium and dietary vitamin C and carotene (P = 0.003). Systolic blood pressure decreased from 127.9 to 125.2 mmHg (2.7 mmHg decrease; 95% confidence interval, -4.6 to -0.8) in the intervention group, whereas it increased from 128.0 to 128.5 mmHg (0.5 increase; -1.3 to 2.3) in the control group. This change was statistically significant (P = 0.007). In contrast, the change in diastolic blood pressure did not significantly differ between the groups. In hypertensive subjects, a significant difference in systolic blood pressure reduction was seen between the groups (P = 0.032).\n Moderate-intensity dietary counseling in free-living healthy subjects achieved significant dietary changes, which resulted in a significant decrease in systolic blood pressure.", "Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial.\n To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women.\n The Women's Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States.\n Participants were randomly assigned to the dietary modification intervention (n = 19,541; 40%) or the comparison group (n = 29,294; 60%). The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern.\n Invasive colorectal cancer incidence.\n A total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention.\n In this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up.\n ClinicalTrials.gov Identifier: NCT00000611.", "The Next Step Trial tested interventions encouraging prevention and early detection practices in automotive-industry employees at increased colorectal cancer risk. This article describes results of the nutrition intervention promoting low-fat, high-fiber eating patterns.\n Twenty-eight worksites (5,042 employees at baseline) were randomized to a 2-year nutrition intervention including classes, mailed self-help materials, and personalized dietary feedback. Control worksites received no intervention. Nutrition outcomes were assessed by mailed food frequency questionnaires (FFQs) Primary nutrition outcomes included percentage energy from fat and fiber density (g/1,000 kcal) at 1 year postrandomization. Secondary outcomes included servings of fruits/vegetables and dietary measures at 2 years postrandomization. Analyses were adjusted for within worksite correlations and baseline covariates. Fifty-eight percent of employees returned FFQs.\n At 1 year, there were modest but statistically significant intervention effects for fat (-0.9 %en), fiber (+0.5 g/1,000 kcal), and fruits/vegetables (+0.2 servings/day) (all P < 0.007). At 2 years, due to significant positive changes in control worksites, intervention effects were smaller, significant for fiber only. Intervention effects were larger in younger (<50 years), active employees and class attendees.\n The nutrition intervention produced significant but modest effects on dietary fat and fiber and fruits/vegetables in these high-risk employees. Age and dose effects suggest younger employees may be more responsive to this intervention.\n Copyright 1999 American Health Foundation and Academic Press.", "High vegetable and fruit (V&F) consumption has been associated with a lower risk of several cancers. However, little is known about the ability of individuals to increase their intakes markedly. In this 1-year randomized, controlled diet intervention study of men and women with a recent history of adenomas, the intervention group (n = 100) was asked to increase V&F intake to at least eight servings per day; the control group (n = 101) continued eating their usual diet. End-point measures included V&F intake assessed by 3-day diet records, plasma carotenoids, serum lipids, urinary sodium and potassium, and body weight. The intervention group increased their daily V&F intake an average of 5.5 servings over 1 year; the control group had an average decrease of 0.5 servings per day (P < 0.001). Plasma total carotenoids, alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin were each statistically significantly elevated over baseline (11-54%) in the intervention group compared with the control group over the duration of follow-up (P < 0.001). Urinary potassium excretion was elevated 14% over baseline in the intervention group compared with no change in the control group (P < 0.001). Modest decreases in the intervention but not the control group were observed for total and low-density lipoprotein cholesterol. Plasma lycopene, triglycerides, high-density lipoprotein cholesterol, body weight, and urinary sodium were not affected by the intervention. V&F intake was significantly increased in this motivated population at higher risk of colon cancer and maintained for at least 12 months, as assessed using diet records and an ensemble of biomarkers.", "This study evaluated the effectiveness of a low-intensity dietary intervention in primary care practice in lowering dietary fat intake and raising dietary fiber intake.\n A randomized controlled trial of 28 physician practices in six primary care clinics enrolled, by telephone, adult patients who had appointments for nonurgent nonacute visits. Of 3490 eligible patients contacted, 2111 completed baseline interview; 86.1% also completed a 12-month follow-up. Physicians gave intervention participants a self-help booklet and a brief motivational message. Changes in fat and fiber from baseline to 12-month follow-up were evaluated.\n Intervention and control groups both reported a decrease in fat intake and an increase in fiber intake. The differential change and 95% confidence interval (CI) for the percentage of energy obtained from fat was -1.2 (CI = -0.71, -1.7) (P = .0015), for grams fiber/1000 kcal 0.32 (CI = -0.066, 0.71) (P = .086), for fat score -0.044 (CI = -0.016, -0.072) (P = .010), and for fiber score 0.036 (CI = 0.011, 0.061) (P = .014), with greater reductions in fat and greater increase in fiber in the intervention group.\n This low-intensity intervention was effective in dietary behavior change.", "Higher plasma micronutrient levels have been associated with decreased cancer risks. The objective of this study was to determine the relative effects of reduced fat and/or increased fruit-vegetable (FV) intakes on plasma micronutrient levels.\n Healthy, premenopausal women with a family history of breast cancer (n = 122) were randomized across four diet arms for one year in a 2 x 2 factorial design study: control, low-fat, high fruit-vegetable and combination low-fat/high FV diets. Levels of plasma micronutrients were measured in plasma at 0, 3, 6 and 12 months.\n The high FV intervention, regardless of fat intake, significantly increased alpha-carotene, beta-carotene and vitamin C levels in plasma. Only the combination high FV, low-fat intervention significantly increased plasma beta-cryptoxanthin and zeaxanthin levels over time. Although alpha-tocopherol was not affected, a potential concern is that the low-fat intervention resulted in significantly decreased both gamma-tocopherol dietary intakes and plasma levels, regardless of whether or not FV intakes were concomitantly increased.\n Unlike alpha-tocopherol, gamma-tocopherol plasma levels were decreased by a low fat diet, perhaps because gamma-tocopherol is not generally added to foods nor widely used in vitamin E supplements. The decreased dietary intakes and plasma levels of gamma-tocopherol with a low-fat diet may have implications for health risks since the biological functions of the different tocopherol isomers have been reported to be distinct.", "This study evaluated a tailored, multiple-component self-help intervention designed to promote lower fat and higher fruit and vegetable consumption.\n Participants were 1,459 adults selected at random, stratified by sex and age (18-34, 35-54, 55-69), from enrollees of a large health maintenance organization. After completing a baseline telephone survey, participants were randomized to receive the intervention (consisting of a computer-generated personalized letter, a motivational phone call, a self-help manual, a package of supplementary materials, computer-generated behavioral feedback based on a self-administered food frequency questionnaire, and newsletters) or to receive no materials. Evaluation was based on 1,205 (86.5%) participants who completed both a 3- and a 12-month follow up survey.\n The intervention effect +/- SE for fat, based on a diet habits questionnaire, was -0.10 +/- 0.02 (P < 0.001), corresponding to a reduction of approximately 0.8 percentage points of percentage energy from fat. For fruits and vegetables, the intervention effect was 0.47 +/- 0.10 servings/day (P < 0.001). Intervention effects were similar across age and sex groups.\n Tailored, self-help interventions can effectively promote dietary change among both men and women and among younger as well as older adults.\n Copyright 2000 American Health Foundation and Academic Press.", "The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber (4.30 g/MJ), high-fruit-and-vegetable (0.84 servings/MJ), low-fat (20% of energy from fat) diet on the recurrence of adenomatous polyps in the large bowel.\n Our goal was to determine whether the PPT intervention plan could effect change in 3 dietary goals and to examine the intervention's effect on the intake of other food groups and nutrients.\n Participants with large-bowel adenomatous polyps diagnosed in the past 6 mo were randomly assigned to either the intervention (n = 1037) or the control (n = 1042) group and remained in the trial for 4 y. Three dietary assessment instruments were used to measure dietary change: food-frequency questionnaires (in 100% of the sample), 4-d food records (in a 20% random cohort), and 24-h dietary recalls (in a 10% random sample).\n Intervention participants made and sustained significant changes in all PPT goals as measured by the dietary assessment instruments; the control participants' intakes remained essentially the same throughout the trial. The absolute differences between the intervention and control groups over the 4-y period were 9.7% of energy from fat (95% CI: 9.0%, 10.3%), 1.65 g dietary fiber/MJ (95% CI: 1.53, 1.74), and 0.27 servings of fruit and vegetables/MJ (95% CI: 0.25, 0.29). Intervention participants also reported significant changes in the intake of other nutrients and food groups. The intervention group also had significantly higher serum carotenoid concentrations and lower body weights than did the control group.\n Motivated, free-living individuals, given appropriate support, can make and sustain major dietary changes over a 4-y period.", "To study the impact of diet and exercise and the combination thereof on cardiovascular risk factors, 157 healthy men aged 35-60 years (mean +/- S.D.; 46.2 +/- 5.0) with slightly to moderately raised cardiovascular risk factors, were randomized to 4 groups, diet (D, n = 40), exercise (E, n = 39), diet plus exercise (DE, n = 39), and no active intervention (controls (C, n = 39)), and investigated at baseline and after 6 months. BMI was significantly reduced in Groups E and DE (mean difference and 95% confidence intervals (CI), -0.3 (-0.5, -0.01) and -0.6 (-0.9, -0.3) kg/m2, respectively). Waist circumference was reduced in all 3 intervention groups (D, E, and DE), -1.3 (-2.5, -0.1), -2.2 (-3.2, -1.3) and -3.0 (-3.9, -2.0) cm, but not in the control group. Blood pressure (BP) was reduced in all 3 intervention groups, systolic BP 4-7 mmHg and diastolic BP 2-6 mmHg. Serum cholesterol was reduced in Group DE, -0.45 (-0.77, -0.13) mmol/l. VLDL-cholesterol was reduced in Groups E and DE, -0.14 (-0.26, -0.03) and -0.09 (-0.18, -0.01) mmol/l, whereas LDL-cholesterol was reduced in Groups D and DE -0.30 (-0.54, -0.06) and -0.35 (-0.64, -0.05) mmol/l. In contrast, neither HDL-cholesterol nor serum triglycerides were influenced by the interventions. According to the coronary risk profile derived from the Framingham study, all 3 intervention groups (D, E, and DE) significantly reduced their estimated 10-year risk (-13, -12, and -14%, respectively). We conclude that even with rather moderate changes in diet and exercise, several important cardiovascular risk factors can be affected and that diet and exercise were about equally effective in reducing cardiovascular risk.", "The Women's Health Trial: Feasibility Study in Minority Populations (WHT:FSMP), a randomized trial of 2208 women, was conducted to investigate three questions. First, can women from minority and low-socioeconomic-status populations be recruited in numbers sufficient to evaluate a dietary intervention designed to lower fat intake. Second, the efficacy of a low fat, increased fruit/vegetable/ grain product intervention for reducing fat consumption. Third, will participation in the intervention lower plasma cholesterol and estradiol levels relative to the controls. The baseline results showed that an adequate number of minority and low SES women could be recruited to test the study hypotheses. A diverse study population of postmenopausal women consuming a high fat diet was recruited: 28% of participants were Black, 16% were Hispanic, 11% had less than a high school level of education, and 15.5% had household incomes of < $15,000.", "To investigate the effectiveness of a non-structured 15-min educational intervention by general practitioners (GPs) on modifications of daily diet among healthy adults.\n Two arms randomized trial lasting 12 months.\n Italian general practitioner wards. Subjects A total of 3,186 men and women aged 18-65 years recruited in the medical ward by their GPs.\n An educational intervention and a brochure on the basics of a healthy diet based on the Italian Guidelines for a Correct Nutrition, 1998. The main study goal was to attain an intake of fruits and vegetables >5 servings per day. Follow-up visit every 6 months. Main outcome measures Weight, blood pressure, and a 40-items Food Frequency Questionnaire.\n The intervention group showed a slightly reduced net intake of meat and a slightly increased net intake of fruits and vegetables, fish products, and olive oil. Body mass index (BMI) changed only in the treatment arm [-0.41 95% confidence interval (95% CI) -0.11 to -0.53]. The net change at 1 year in the intervention arm was +1.31 (CI 0.90-4.39) for fruits and vegetables, and -0.22 (-0.11 to -0.69) for meat (portions per week). We also computed a 'healthy diet score' reflecting compliance with recommended dietary habits. In the intervention group, the mean score at recruitment was significantly lower than the mean score at the end of follow-up (Crude score change = 0.29; CI 0.19-0.48). No differences were observed in the control group (Crude score change = -0.04; CI -0.22-0.02). The difference in score from baseline to the final visit, comparing the intervention vs the control group, was statistically significant (P < 0.001) (MANOVA adjusted by sex, BMI, education, and time).\n A brief educational intervention by GPs can induce multiple diet changes that may lower BMI and potentially reduce chronic disease risk in generally healthy adults.", "Despite formal recommendations for dietary change to reduce the incidence of ischaemic heart disease, the acceptability and effectiveness of the proposed diets have not been well investigated in population based studies. In this preliminary investigation of nutritional advice in a well population, subjects in one group practice were randomized to receive either dietary instruction or simple follow up without instruction. The dietary recommendations were well received, and a substantial proportion of subjects reported altering their diets in accordance with them. There were modest beneficial changes in plasma lipid levels among men. Thus, using general practice as an avenue for promoting dietary change is feasible, and may be effective among men.", "Current cancer prevention recommendations include reducing consumption of fat and increasing consumption of fruits and vegetables.\n Healthy women health maintenance organization members (n = 616) ages 40-70 were randomly assigned to either a nutrition intervention or a control intervention unrelated to diet. Intervention included two 45-min counseling sessions plus two brief follow-up telephone contacts. Counseling sessions included a 20-min, interactive, computer-based intervention using a touch-screen format. Intervention goals were reducing dietary fat and increasing fruit and vegetable consumption. Outcome measures included a food frequency questionnaire and the Fat and Fiber Behavior Questionnaire (FFBQ). Total serum cholesterol was also measured at baseline and 12 months.\n Twelve-month follow-up data showed improvements on all dietary outcome variables. Compared to the control, intervention participants reported significantly less fat consumption (3.75 points less for percentage of energy from fat), significantly greater consumption of fruit and vegetables combined (0.93 more servings per day), and a significant reduction in a behavioral measure of fat consumption (0.20 point change in the FFBQ). Group differences in total serum cholesterol, while in the desired direction, were not significant.\n In appropriate circumstances, moderate-intensity dietary interventions can show significant effects for periods of at least 1 year.", "A positive family history of coronary heart disease alone confers an increased risk, which may be affected by untreated hypercholesterolemia. Dietary counseling is a first-line treatment approach. To determine whether nurse counseling can provide additional benefits over usual physician efforts to lower dietary fat in high-risk persons, 117 apparently healthy adult siblings of persons with premature coronary heart disease were counseled by a registered nurse using adapted national guidelines. Reductions in total fat, saturated fat, and cholesterol were significantly greater in the nurse group compared to those in the usual care group. Total fat intake decreased by 14 g in the nurse group, compared with an increase of 5 g in the usual care group (p=0.0001). Assignment to the nurse group was also a significant predictor of a greater reduction in the percentage of total fat calories (p=0.008). The authors conclude that a registered nurse may serve as a complement to usual care in efforts to lower dietary fat and cholesterol in high-risk families. (c)2001 CHF, Inc." ]

[ "9464734" ]

[ "Nitroglycerin to facilitate fetal extraction during cesarean delivery." ]

[ "To determine the efficacy of nitroglycerin in easing fetal extraction in elective cesarean deliveries in comparison with placebo and to collect maternal and fetal pharmacologic data after administration of nitroglycerin.\n This randomized, double-blind clinical and descriptive pharmacokinetic study was carried out at the gynecology departments at Virchow Hospital and Charité Hospital (both university hospitals of Humboldt University, Berlin, Germany) between June 1994 and July 1996 in patients scheduled for elective cesarean delivery under general anesthesia. At the time of the uterine puncture incision, either 0.25 mg or 0.5 mg of nitroglycerin or a physiologic saline solution was administered as an intravenous bolus. Intraoperatively, maternal and neonatal pulse rates and blood pressure were monitored closely. The surgeons estimated reduction in uterine tone and the ease of fetal extraction by means of defined scales. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and from umbilical blood.\n Ninety-seven patients were included in the statistical evaluation of the study; 32 received 0.25 mg of nitroglycerin, 34 received 0.5 mg of nitroglycerin, and 31 received placebo. The evaluation of the surgeons' estimation revealed no significant difference in ease of fetal extraction (statistical power 0.7) and no significant reduction in uterine tone under treatment with both nitroglycerin dosages in comparison with placebo. Only substance-specific maternal side effects were noted. The neonates' conditions were not affected by administration of nitroglycerin. The median fetal-maternal ratio of venous nitroglycerin plasma levels was approximately 1:400 in the 0.25-mg nitroglycerin group and 1:160 in the 0.5-mg nitroglycerin group. Approximately 11-12 times more nitroglycerin was detected in the venous umbilical branch than in the arterial branch.\n Administration of nitroglycerin leads to no clinically relevant easing of fetal extraction, at least not in elective cesarean deliveries after the 34th week of gestation. With regard to pharmacokinetics, the measured median fetal-maternal venous nitroglycerin concentration was 1:400 in the 0.25-mg group and 1:160 in the 0.5-mg group." ]

[ "94267", "10148140", "6351517", "6172176", "6182661" ]

[ "The cost effectiveness of dextranomer and eusol in the treatment of infected surgical wounds.", "Dextranomer (Debrisan) paste in post-operative wounds. A controlled study.", "Treatment of infected surgical wounds with Varidase.", "Report of a prospective trial of dextranomer beads (Debrisan) and silicone foam elastomer (Silastic) dressings in surgical wounds.", "[Debrisan compared with chloramine packs in the treatment of postoperative wounds]." ]

[ "nan", "The clinical effect of dextranomer paste (Debrisan) in post-operative wounds (20 patients) was compared with the standard treatment in our department (polyvinylpyrrolidone, 20 patients) in a randomized study. All variables dealing with cleansing, inflammation-reducing effect and signs of ongoing healing were studied. Dextranomer paste appeared to be significantly better than polyvinylpyrrolidone in wounds with a high degree of pus and debris. No side-effects were observed in the dextranomer paste group. One patient in the control group showed an allergic reaction (oedema and erythema) and was withdrawn from the study.", "In 18 patients with subcutaneous wound infection after laparotomy the wounds were randomly treated with normal saline solution or with Varidase solution after complete opening, according to a double-blind system. Treatment was discontinued when the wound was clean enough for secondary suture or the patient could be discharged from hospital. Three patients, in whom the treatment was not completed because of intercurrent complications, were excluded from the evaluation. When the double-blind code was broken, 11 patients were found to have received saline treatment and 7 Varidase. The duration of the wound-dressing periods averaged 13.45 +/- 6.77 days in the former group and 5.00 +/- 2.16 in the latter. The difference is statistically significant.", "A prospective randomized controller trial of dextranomer beads (Debrisan) and silicone foam elastomer (Silastic) dressings in open infected surgical wounds has been performed. The results indicate that the healing time for wounds treated by Debrisan (n = 25) and elastomer (n = 25) is similar, being 40.92 +/- 3.98 and 36.90 +/- 3.18 days respectively. The time taken for wounds to become pain-free was similar in both treatment groups, as was the persistence of signs in the wounds of erythema, oedema and slough. Comparison of cost reveals the elastomer dressing to be considerably cheaper than Debrisan.", "nan" ]

[ "9536565", "10692752" ]

[ "Sumatriptan suppositories for the acute treatment of migraine. S2B351 Study Group.", "A dose-defining study of sumatriptan suppositories in the acute treatment of migraine." ]

[ "A randomised, double-blind, parallel-group, placebo-controlled trial was undertaken to assess the efficacy and tolerability of the sumatriptan suppository in 184 patients with acute migraine. Patients used a sumatriptan suppository (12.5 mg or 25 mg) or placebo at home for the treatment of a moderate or severe migraine attack and those who experienced headache recurrence within 24 hours of dosing had the option to repeat the dose. By 2 hours post-dose, 68% of patients in the sumatriptan 25 mg group and 47% of patients in the sumatriptan 12.5 mg group compared with 25% of placebo patients achieved headache relief. Relief rates 2 hours post-dose for nausea, vomiting, photophobia and phonophobia were similar to those reported 2 hours post-dose for headache. Post hoc review of the recurrence data showed that administration of a second suppository was effective in alleviating recurrent headache in over 80% of the sumatriptan-treated patients experiencing recurrence. No serious or unusual adverse events were reported, and the pattern and incidence of adverse events did not vary as a function of dose. These data demonstrate that the sumatriptan suppository is a well-tolerated, effective treatment for the acute treatment of migraine pain and its associated symptoms.", "In this dose-ranging, randomised, multinational, multicentre, double-blind, placebo-controlled, parallel group study, 431 patients treated a single migraine attack with study medication: sumatriptan suppository 6 mg, 12.5 mg, 25 mg, 50 mg, 100 mg, or placebo. Patients were treated in the clinic with a single dose in suppository form. All doses of sumatriptan, except 6 mg, were significantly better than placebo (p < 0.004) and achieved similar rates of headache relief within two hours of dosing. The highest response rate was in the 25 mg group (72%) compared with placebo (37%) (p < 0.001). Fewer patients required rescue medication in the active groups (1% 100 mg to 13% 6 mg) compared with placebo (17%), and more patients were able to work and function normally two hours after dosing (41%, 100 mg; 20%, placebo). The overall incidence of adverse events was similar in the placebo, 6 mg and 12.5 mg groups (14-17%) but higher in the 25 mg, 50 mg and 100 mg groups (25%, 32% and 29% respectively). Analysis of plasma sumatriptan levels indicated rapid rectal absorption for all doses (median tmax = 1.0 hr). It is concluded that sumatriptan, in doses above 6 mg, is an effective and well tolerated treatment for acute migraine. From this study doses of 12.5 mg and 25 mg sumatriptan were identified as having the best efficacy/safety profile and were evaluated further." ]

[ "1569347", "12172535", "2502065" ]

[ "A randomized, double-blind study of the efficacy of fleroxacin versus trimethoprim-sulfamethoxazole in men with culture-proven chancroid.", "A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis.", "Evaluation of fleroxacin (RO 23-6240) as single-oral-dose therapy of culture-proven chancroid in Nairobi, Kenya." ]

[ "Chancroid is linked to the spread of human immunodeficiency virus type 1 (HIV-1) in East Africa. Effective, easily administered therapy is a priority for the control of Haemophilus ducreyi. The efficacy of a single oral dose of fleroxacin, 400 mg, was compared to a 3-day oral course of trimethoprim-sulfamethoxazole (TMP-SMZ), 160/800 mg, twice daily for the treatment of chancroid in 98 HIV-1-seronegative men in Nairobi, Kenya. No differences were noted between the two groups with respect to demographic characteristics, sexual behavior, and clinical characteristics. Culture-proven failure occurred in 1 (3%) of 36 fleroxacin-treated patients and in 11 (30%) of 37 TMP-SMZ-treated patients (P = .005). Fleroxacin, as a single oral dose, is an effective treatment for culture-proven chancroid in patients who are HIV-1 seronegative. TMP-SMZ is no longer predictably effective due to the recent emergence of resistance to both sulfonamides and to trimethoprim.", "Penicillin is the only medication currently recommended for treatment of early syphilis in non-penicillin-allergic patients. Preliminary data suggest that azithromycin may be effective for syphilis therapy.\n This was a randomized, comparative pilot study of intramuscular injections of benzathine penicillin G and two oral azithromycin regimens for treatment of syphilis.\n We randomly assigned patients with early syphilis to treatment with either intramuscular injections of 2.4 million units of benzathine penicillin G or azithromycin administered orally, either as a single 2.0-g dose or as two 2.0-g doses given 1 week apart. Serological response to therapy was evaluated at 3, 6, 9, and 12 months following therapy. Participants whose rapid plasma reagin (RPR) test became nonreactive or whose RPR titer decreased > or =2 dilutions were classified as responding to therapy. When serological tests did not show a response to therapy, the treatment was classified as a failure if RPR titers increased > or =2 dilutions. Nonresponders were those whose serologic titers remained within +/-1 dilution of the initial RPR titer.\n Cumulative response rates were as follows: benzathine penicillin G, 86% (12 of 14); azithromycin, 2.0-g single dose, 94% (16 of 17); and azithromycin, two 2.0-g doses given 1 week apart, 83% (24 of 29). Therapy failed for one patient treated with benzathine penicillin and one patient treated with the two-dose azithromycin regimen, whereas in six patients the clinical manifestations of infection resolved but there was no serological response.\n Oral therapy with 2.0 g of azithromycin as a single dose or as two doses 1 week apart is a promising alternative to therapy with benzathine penicillin G for syphilis and should be studied further.", "Chancroid is gaining importance as a sexually transmitted disease because of its association with transmission of human immunodeficiency virus type 1 (HIV-1). Effective, simply administered therapy for chancroid is necessary. Fleroxacin is effective against Haemophilus ducreyi in vitro. We performed an initial randomized clinical trial to assess the efficacy of fleroxacin for treatment of chancroid in Nairobi, Kenya. Fifty-three men with culture-positive chancroid were randomly assigned to receive either 200 mg (group 1) or 400 mg (group 2) of fleroxacin as a single oral dose. Groups 1 and 2 were similar with regard to severity of disease, bubo formation, and HIV-1 status. A satisfactory clinical response to therapy was noted in 23 of 26 patients (88%) in group 1 and 18 of 23 patients (78%) in group 2. Bacteriological failure occurred in 1 of 26 evaluable patients (4%) in group 1 and 4 of 23 evaluable patients (17%) in group 2. Two of 37 HIV-1-seronegative men (5%) and 3 of 11 HIV-1-infected men (27%) were bacteriological failures. Fleroxacin, 200 or 400 mg as a single oral dose, is efficacious therapy for microbiologically proven chancroid in patients who do not have concurrent HIV-1 infection. Among HIV-1-infected men, a single dose of 200 or 400 mg of fleroxacin is inadequate therapy for chancroid." ]

[ "9584032", "9477538", "18591366", "12699022", "9215505", "19652099", "17046506", "10650733", "11777112", "11495184", "23084163", "19937385", "8899140", "16027537", "20401635", "9519580", "21571742" ]

[ "An evaluation of Safe Dates, an adolescent dating violence prevention program.", "An evaluation of a dating violence prevention program for middle school students.", "Rape prevention with college men: evaluating risk status.", "Dating violence prevention with at-risk youth: a controlled outcome evaluation.", "Efficacy of a dating violence prevention program on attitudes justifying aggression.", "A school-based program to prevent adolescent dating violence: a cluster randomized trial.", "Impact of a school-based dating violence prevention program among Latino teens: randomized controlled effectiveness trial.", "The longitudinal effects of a rape-prevention program on fraternity men's attitudes, behavioral intent, and behavior.", "The evaluation of a sexual assault risk reduction program: a multisite investigation.", "Evaluating a prevention program for teenagers on sexual coercion: a differential effectiveness approach.", "\"Coaching boys into men\": a cluster-randomized controlled trial of a dating violence prevention program.", "An evaluation of a mixed-gender sexual assault prevention program.", "Rape prevention with high-risk males: short-term outcome of two interventions.", "Effects of a CD-ROM educational program on sexual knowledge and attitude.", "A brief motivational intervention for physically aggressive dating couples.", "Evaluation of an intervention to change attitudes toward date rape.", "Preventing sexual aggression among college men: an evaluation of a social norms and bystander intervention program." ]

[ "This study assessed the effects of the Safe Dates program on the primary and secondary prevention of adolescent dating violence.\n Fourteen schools were randomly allocated to treatment conditions. Eighty percent (n=1886) of the eighth and ninth graders in a rural county completed baseline questionnaires, and 1700 (90%) completed follow-up questionnaires.\n Treatment and control groups were comparable at baseline. In the full sample at follow-up, less psychological abuse, sexual violence, and violence perpetrated against the current dating partner were reported in treatment than in control schools. In a subsample of adolescents reporting no dating violence at baseline (a primary prevention subsample), there was less initiation of psychological abuse in treatment than in control schools. In a subsample of adolescents reporting dating violence at baseline (a secondary prevention subsample), there was less psychological abuse and sexual violence perpetration reported at follow-up in treatment than in control schools. Most program effects were explained by changes in dating violence norms, gender stereotyping, and awareness of services.\n The Safe Dates program shows promise for preventing dating violence among adolescents.", "A study was undertaken to determine the effectiveness of a 5-session relationship violence prevention program involving a middle school of predominantly African-American students. A composite measure assessed changes in knowledge, attitudes, and methods of dealing with relationship violence. A pretest-posttest control group design was used. Results indicated that treatment group scores were significantly higher than control group scores at posttest (p < .001) and treatment group posttest scores were significantly higher than pretest scores (p < .001). There were significant differences in scores between regular-level students and those with a higher level of academic ability (advanced students). Within the treatment group, there was a level-by-gender interaction revealing that male advanced students made the highest gains. In examining specific items, improvements were made in knowledge about relationship violence and attitudes about nonphysical violence. No changes were seen in attitudes about physical violence or in methods of dealing with relationship violence.", "This study evaluates the effectiveness of a theoretically based rape prevention intervention with college men who were at high or low risk to perpetrate sexually coercive behavior. Participants (N = 146) are randomly assigned to the intervention or control group. Outcomes include rape myth acceptance, victim empathy, attraction to sexual aggression, sex-related alcohol expectancies, and behavioral indicators, measured across three time points. Positive effects are found for rape myth acceptance, victim empathy, attraction to sexual aggression, and behavioral intentions to rape. Only rape myth acceptance and victim empathy effects sustain at the 5-week follow-up. High-risk men are generally unaffected by the intervention although low-risk men produced larger effects than the entire sample. Results suggest rape prevention studies must assess risk status moderation effects to maximize prevention for high-risk men. More research is needed to develop effective rape prevention with men who are at high risk to rape.", "This study evaluated a community-based intervention to help at-risk teens develop healthy, nonabusive relationships with dating partners. Participants were 158 14-16-year-olds with histories of child maltreatment who were randomly assigned to a preventive intervention group or a no-treatment control group. They completed measures of abuse and victimization with dating partners, emotional distress, and healthy relationship skills at bimonthly intervals when dating someone. Intervention consisted of education about healthy and abusive relationships, conflict resolution and communication skills, and social action activities. Growth curve analyses showed that intervention was effective in reducing incidents of physical and emotional abuse and symptoms of emotional distress over-time. Findings support involvement of youths in reducing the cycle of violence as they initiate dating in midadolescence.", "The purpose of this pilot study was to evaluate a five-session dating violence prevention curriculum in terms of its effect on attitudes justifying the use of dating violence.\n The curriculum was implemented in all health classes in a Long Island, New York, school. A total of 193 students participated (boys, n = 106; girls, n = 87). A quasi-experimental design was used to evaluate change in attitudes justifying dating violence, with health classes randomly assigned to the treatment or no-treatment conditions.\n Pre- to postprogram assessments indicated that there were significant decreases in overall attitudes justifying the use of dating violence as a means to resolve conflict among students exposed to the curriculum material, whereas those who were not exposed did not show attitude change from pre- to postprogram evaluation.\n The curriculum shows promise as an effective tool for changing attitudes condoning dating violence. Future research is needed to determine whether the observed attitude change is also linked to reduction in aggressive behaviors.", "To determine whether an interactive curriculum that integrates dating violence prevention with lessons on healthy relationships, sexual health, and substance use reduces physical dating violence (PDV).\n Cluster randomized trial with 2.5-year follow-up; prespecified subgroup analyses by sex.\n Grade 9 health classes.\n A total of 1722 students aged 14-15 from 20 public schools (52.8% girls). Intervention A 21-lesson curriculum delivered during 28 hours by teachers with additional training in the dynamics of dating violence and healthy relationships. Dating violence prevention was integrated with core lessons about healthy relationships, sexual health, and substance use prevention using interactive exercises. Relationship skills to promote safer decision making with peers and dating partners were emphasized. Control schools targeted similar objectives without training or materials.\n The primary outcome at 2.5 years was self-reported PDV during the previous year. Secondary outcomes were physical peer violence, substance use, and condom use. Analysis was by intention-to-treat.\n The PDV was greater in control vs intervention students (9.8% vs 7.4%; adjusted odds ratio, 2.42; 95% confidence interval, 1.00-6.02; P = .05). A significant group x sex interaction effect indicated that the intervention effect was greater in boys (PDV: 7.1% in controls vs 2.7% in intervention students) than in girls (12.1% vs 11.9%). Main effects for secondary outcomes were not statistically significant; however, sex x group analyses showed a significant difference in condom use in sexually active boys who received the intervention (114 of 168; 67.9%) vs controls (65 of 111 [58.6%]) (P < .01). The cost of training and materials averaged CA$16 per student.\n The teaching of youths about healthy relationships as part of their required health curriculum reduced PDV and increased condom use 2.5 years later at a low per-student cost.", "Given the high rate of dating violence between teens and associated deleterious outcomes, the need for effective prevention and early intervention programs is clear. Break the Cycle's Ending Violence curriculum, a three-class-session prevention program focused on legal issues, is evaluated here for its impact on Latino/a youth.\n Tracks within large urban high schools that had at least 80% Latino/a students were randomized to immediate or delayed curriculum. Classrooms were randomly selected within tracks and individual student outcomes were assessed pre- and postintervention and six months later.\n Students in intervention classrooms showed improved knowledge, less acceptance of female-on-male aggression, and enhanced perception of the helpfulness and likelihood of seeking assistance from a number of sources immediately after the program. Improved knowledge and perceived helpfulness of an attorney were maintained six months later. There were no differences in recent abusive/fearful dating experiences or violence victimization or perpetration.\n The Ending Violence curriculum has an impact on teen norms, knowledge, and help-seeking proclivities that may aid in early intervention for dating violence among Latino/a students.", "Rape myth acceptance, likelihood of raping, and sexually coercive behavior of 145 fraternity men randomly assigned to a control group or a rape-prevention program were surveyed. One third of 23 fraternities on a mid-Atlantic public university campus volunteered to participate in the study. The rape-prevention intervention consisted of \"the men's program,\" a victim empathy-based presentation titled \"How to help a sexual assault survivor: What men can do.\" Although no evidence of change in sexually coercive behavior was found, significant 7-month declines in rape myth acceptance and the likelihood of committing rape were shown among program participants. In the case of rape myth acceptance, the 7-month decrement remained lower in the participant group than in the control group. Implications of using these initial findings from the men's program for rape-prevention programming are discussed.", "This article summarizes the results of the Ohio University Sexual Assault Risk Reduction Project, which is a program designed to reduce college women's risk for sexual assault. The program was evaluated at 2 separate universities with 762 women. Participants were randomly assigned either to the program or to the no-treatment comparison group, and they completed measures that assessed sexual victimization, dating behaviors, sexual communication, and rape empathy at the pretest and at the 2-month and 6-month follow-ups. At the 2-month follow-up, there were no differences between the groups on any of the outcome measures. However, those women who were moderately victimized during the 2-month follow-up were significantly less likely to be revictimized during the 6-month follow-up period if they participated in the program.", "The authors evaluated a coeducational program for teenagers on preventing sexual coercion in dating situations. Students examined individual and social attitudes underlying coercive sexual behavior and learned communication skills aimed at preventing or dealing with unwanted sexual advances. Instruction was enhanced by video and an interactive video \"virtual date.\" Outcomes were assessed using sexual attitude scales with a sample of 458 high school students. Student health education classes were randomly assigned to either a treatment or a control condition. Findings, based on a latent variable model of differential effectiveness, showed that students in the treatment group with initial coercive attitude scores at or above the mean benefited significantly more than students with the same range of scores in the control group.", "Dating violence (DV)--physical, sexual, and psychological aggression in adolescent romantic relationships--is prevalent among youth. Despite broad calls for primary prevention, few programs with demonstrated effectiveness exist. This cluster-randomized trial examined the effectiveness of a DV perpetration prevention program targeting coaches and high school male athletes.\n The unit of randomization was the high school (16 schools), and the unit of analysis was the athlete (N = 2,006 students). Primary outcomes were intentions to intervene, recognition of abusive behaviors, and gender-equitable attitudes. Secondary outcomes explored bystander behaviors and abuse perpetration. Regression models for clustered, longitudinal data assessed between-arm differences in over-time changes in mean levels of continuous outcomes in 1,798 athletes followed up at 3 months.\n Intervention athletes' changes in intentions to intervene were positive compared with control subjects, resulting in an estimated intervention effect of .12 (95% CI: .003, .24). Intervention athletes also reported higher levels of positive bystander intervention behavior than control subjects (.25, 95% CI: .13, .38). Changes in gender-equitable attitudes, recognition of abusive behaviors, and DV perpetration were not significant. Secondary analyses estimated intervention impacts according to intensity of program implementation. Compared with control subjects, athletes exposed to full-intensity implementation of the intervention demonstrated improvements in intentions to intervene (.16, 95% CI: .04, .27), recognition of abusive behaviors (.13, 95% CI: .003, .25), and positive bystander intervention (.28, 95% CI: .14, .41).\n This cluster-randomized controlled trial supports the effectiveness of a school athletics-based prevention program as one promising strategy to reduce DV perpetration.\n Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.", "This study evaluated the short-term effectiveness of a mixed-gender sexual assault prevention program developed for college students. Program participants (n = 177) were compared to non-program participants (n = 132) prior to the program and during a 2-week follow-up period on measures of rape myths, victim empathy, perceived negative consequences and estimated likelihood of committing rape, sexual communication, sexual assault awareness, and risky dating behavior. The prevention program was effective at increasing men's victim empathy and decreasing their adherence to rape myths but ineffective at changing women's assault-related knowledge, participation in risky dating behaviors, and sexual communication strategies. Limitations of the study and directions for future research in sexual assault prevention are addressed. Editors' Strategic Implications: This study provides an important example of the limitations of a single session prevention programming approach (even if it is well designed and executed) in addressing a systemic and pervasive problem like sexual assault on college campuses.", "Two model-based interventions designed to reduce the amount of date rape attempted by male college students were developed and evaluated. The Rape Supportive Cognitions (RSC) intervention targeted commonly held false beliefs that promote or condone coercive sexual behavior. The Victim Empathy/Outcome Expectancies (VE/OE) intervention targeted poor victim empathy and problematic rape outcome expectancies. Seventy-four high-risk subjects as determined by scores on the Attraction to Sexual Aggression scale (ASA) (Malamuth, 1989) were randomly assigned to one of the treatment groups (RSC or VE/OE) or to a no-treatment control group. Treatment effects were assessed using subjects' pre- and posttreatment scores on the ASA, the Rape Myth Acceptance, the Acceptance of Interpersonal Violence, and the Adversarial Sexual Beliefs scales (Burt, 1980), as well as subjects' posttreatment scores on the Rape Conformity Assessment (Schewe and O'Donohue, 1995). Results indicated that both treatments were significantly more effective than no treatment. The RSC group showed clinically significant changes on three of the five dependent measures, while the VE/OE group evidenced clinically significant changes on only one measure. This is the first well-controlled rape prevention study to demonstrate clear improvements in treated high-risk males over control group subjects.", "This study evaluated a CD-ROM educational program in sexual violence prevention for middle school students. A randomized control-group pretest-posttest design was used. Seventy-nine students were randomly assigned to either an experimental (n = 39) or control (n = 40) group. The experimental group watched the CD-ROM, whereas the control group did not. Both groups were pretested for the levels of knowledge and attitude about sexual violence prevention prior to intervention. A CD-ROM titled Educational Program for the Prevention of Sexual Violence was used for the intervention. The instrument contains 32 true-false items that measure knowledge level and 20 items comprising a four-point Likert-type scale that measure the attitude to sexual violence. There was a significant increase in knowledge in the experimental group, while no differences on attitude were found between the experimental and control groups. A CD-ROM-based program can be effective for delivering instructions on sexual violence prevention in the classroom.", "Motivational interviewing is a brief non-confrontational intervention designed to enhance motivation to reduce harmful behavior (Miller and Rollnick 2002). The purpose of this study was to examine the effectiveness of motivational interviewing as a targeted prevention approach for partner aggression in emerging adulthood. Participants were 50 college dating couples between 18 and 25 years old who reported at least one act of male-to-female physical aggression in their current relationships. After completing a 2-hour assessment session, half of all couples were randomly assigned to a 2-hour individualized motivational feedback session targeting physical aggression and risk factors for aggression. The remaining couples received minimal, non-motivational feedback. Follow-up surveys were conducted 3, 6, and 9 months later. Hierarchical linear modeling analyses indicated that, compared to the control condition, the motivational feedback intervention led to reductions in physical aggression and harmful alcohol use and to less acceptance of female psychological aggression and male psychological aggression (among women only). Lagged analyses indicated that changes in physical aggression were predicted by reductions in psychological aggression and by lower acceptance of both male and female psychological aggression. Reductions in physical aggression predicted lower anxiety and greater relationship investment and male relationship commitment over time. These findings suggest that a brief motivational intervention is a useful prevention approach for high-risk dating couples, with benefits to both individual and relationship functioning.", "The prevalence of date rape among college students is a major concern. Although much research has been done on risk factors for date rape, few researchers have specifically described interventions for the various stages of developing a date-rape prevention program. Previous programs have often relied on educational videos that feature a \"typical\" date-rape scenario, a format that some researchers suggest may have a negative effect on the way people engage in aggressive sexual behavior. A less violent theatrical production based on social learning theory and risk-factor reduction that resulted in a significant improvement in attitudes related to date rape among both male and female students at an elite Texas university is described.", "Men and women living in randomly selected 1st-year dormitories participated in tailored single-sex sexual assault prevention or risk-reduction programs, respectively. An evaluation of the men's project is presented (N = 635). The program incorporated social norms and bystander intervention education and had an impact on self-reported sexual aggression and an effect on men's perceptions that their peers would intervene when they encountered inappropriate behavior in others. Relative to the control group, participants also reported less reinforcement for engaging in sexually aggressive behavior, reported fewer associations with sexually aggressive peers, and indicated less exposure to sexually explicit media." ]

[ "16124349", "9081959", "17174705", "19564902" ]

[ "Biochemical and clinical profile after organophosphorus poisoning--a placebo-controlled trial using pralidoxime.", "Incidence of intermediate syndrome in organophosphorous poisoning.", "Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial.", "Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial." ]

[ "Organophosphorus (OP) compounds are the most common suicidal poison in developing countries and mortality continues to be high.\n A study was done to see butyryl cholinesterase (BuChE) profile after OP poisoning in pralidoxime (P2AM) and placebo treated cases. Highest recommended dose of P2AM was used to study the reactivation of cholinesterase. Clinical outcomes like, correlation of BuChE and severity of poisoning, mortality and complications like Type I and II paralysis, need for ventilation and ICU stay were also studied.\n Twenty one cases of moderate and severe poisoning with OP compounds were included in the study. Mean BuChE levels came up gradually over 6-7 days, some taking up to two weeks. There was no. difference between the treatment and placebo groups. BuChE levels did not correlate with severity of poisoning nor did it correlate with Type I or II paralysis, need for ventilation, ICU stay or mortality.\n Treatment with P2AM does not make any difference in BuChE reactivation or complications of moderate and severe OP poisoning. We have not been using P2AM for OP poisoning in our medical ICU with good patient outcomes.", "Seventy two patients admitted to the Intensive Care Unit following ingestion of organophosphorus compounds were studied prospectively with two different doses of pralidoxime (PAM). One group received 1 gm immediately after admission and no further PAM and the other group received infusion of PAM, 1 gm 8 hourly for four days (total 12 gms). The incidence of type II paralysis or intermediate syndrome was 47%. We observed a higher incidence in the 4 days of infusion of PAM group (61%) (20 patients) as compared to the single Bolus dose group (39%) (13 patients). Relative risk 1.48 (confidence interval = 0.9-2.4).", "The role of oximes for the treatment of organophosphorus pesticide poisoning has not been conclusively established. We aimed to assess the effectiveness of a constant pralidoxime infusion compared with repeated bolus doses to treat patients with moderately severe poisoning from organophosphorus pesticides.\n 200 patients were recruited to our single-centre, open randomised controlled trial after moderately severe poisoning by anticholinesterase pesticide. All were given a 2 g loading dose of pralidoxime over 30 min. Patients were then randomly assigned to control and study groups. Controls were given a bolus dose of 1 g pralidoxime over 1 h every 4 h for 48 h. The study group had a constant infusion of 1 g over an hour every hour for 48 h. Thereafter, all patients were given 1 g every 4 h until they could be weaned from ventilators. Analysis was by intention to treat. Primary outcome measures were median atropine dose needed within 24 h, proportion of patients who needed intubation, and number of days on ventilation. The study is registered at http://www.clinicaltrials.gov with the identifier NCT00333944.\n 100 patients were assigned the high-dose regimen, and 100 the control regimen. There were no drop-outs. Patients receiving the high-dose pralidoxime regimen required less atropine during the first 24 h than controls (median 6 mg vs 30 mg; difference 24 mg [95% CI 24-26, p<0.0001]). 88 (88%) and 64 (64%) of controls and high-dose patients, respectively, needed intubation during admission to hospital (relative risk=0.72, 0.62-0.86, p=0.0001). Control patients required ventilatory support for longer (median 10 days vs 5 days; difference 5 days [5-6, p<0.0001]).\n A high-dose regimen of pralidoxime, consisting of a constant infusion of 1 g/h for 48 h after a 2 g loading dose, reduces morbidity and mortality in moderately severe cases of acute organophosphorus-pesticide poisoning.", "Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit.\n We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit.\n Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required." ]

[ "8175136", "8100153", "8003650", "7657280", "12190178", "7729640", "1980654", "10782903", "2551765", "9051880", "8174890", "1674105", "8315262" ]

[ "The Canadian Multicenter Double-blind Randomized Controlled Trial of ursodeoxycholic acid in primary biliary cirrhosis.", "Ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a short-term, randomized, double-blind controlled, cross-over study with long-term follow up.", "A two year controlled trial examining the effectiveness of ursodeoxycholic acid in primary biliary cirrhosis.", "A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis.", "Ursodeoxycholic acid for primary biliary cirrhosis: final results of a 12-year, prospective, randomized, controlled trial.", "A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid.", "A multi-center double-blind controlled trial of ursodeoxycholic acid for primary biliary cirrhosis.", "Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver.", "Ursodeoxycholic acid in primary biliary cirrhosis: results of a controlled double-blind trial.", "Ursodeoxycholic acid treatment in patients with primary biliary cirrhosis. A Swedish multicentre, double-blind, randomized controlled study.", "Ursodeoxycholic acid in the treatment of primary biliary cirrhosis.", "A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group.", "Ursodeoxycholic acid for symptomatic primary biliary cirrhosis. Preliminary analysis of a double-blind multicenter trial. Italian Multicenter Group for the Study of UDCA in PBC." ]

[ "Ursodeoxycholic acid, a dihydroxyl bile acid normally present in human beings in minimal amounts, becomes incorporated into the bile salt pool when taken orally. In cholestasis, bile acids are retained in the liver and are hepatotoxic. Ursodeoxycholic acid is the least-known hepatotoxic bile acid, has choleretic properties and is reported to benefit patients with chronic cholestasis. In a nationwide Canadian controlled trial, 222 patients with primary biliary cirrhosis were treated with ursodeoxycholic acid (14 mg/kg/body wt/day) or placebo for 24 mo. Only patients with a diagnosis confirmed by liver biopsy and serum positive for antimitochondrial antibodies were enrolled; 88% were symptomatic on entry. The primary outcome measure was percent change in total serum bilirubin from baseline to final follow-up. Treated patients (111) and controls (111) were comparable with regard to age, gender, biochemical parameters and liver histological condition. Although treatment was not associated with any improvement in symptoms, ursodeoxycholic acid therapy caused the bilirubin to fall significantly within the first 3 mo of therapy (p < 0.001). Significant falls in serum alkaline phosphatase, aminotransferases, cholesterol and IgM levels were also noted in the treated group. Improvement in some histological features was observed but there was no difference between the groups in the number of patients who reached the endpoints of death or liver transplantation. Ursodeoxycholic acid, given to patients with primary biliary cirrhosis, leads to an improvement in serum markers of cholestasis. A larger sample size is needed to determine whether ursodeoxycholic acid therapy has a beneficial effect on the survival of patients with primary biliary cirrhosis.", "In order to evaluate the efficacy of ursodeoxycholic acid (UDCA) in the treatment of Chinese patients with primary biliary cirrhosis, a short-term, randomized, double-blind controlled, cross-over study was done with long-term follow up. In the first part of the study, 12 patients were randomly chosen to receive either UDCA 600 mg/day for 3 months followed by a placebo for 3 months or a placebo for 3 months followed by UDCA for 3 months. The clinical symptoms of pruritus improved when the patients were receiving UDCA but became worse when receiving a placebo. Mean serum levels of alkaline phosphatase (ALPase), gamma-glutamyl transferase (gamma-GT), total bilirubin, cholesterol, alanine aminotransferase (ALT) and aspartate aminotransferase all decreased below the baseline values when receiving UDCA treatment and all increased above the baseline values when receiving the placebo. The difference was statistically significant. In the second part of the study, 19 patients received long-term UDCA treatment (mean 20 months). The clinical symptoms of pruritus improved in 90% of the pruritic patients. Serum levels of ALPase, gamma-GT and ALT fell significantly from the pretreatment values, 6, 12 and from the mean 20 months after UDCA treatment. Serum levels of total bilirubin fell significantly 6 and 12 months after UDCA treatment but did not reach statistical significance at the last follow up. No patient lost antimitochondrial antibody and elevated immunoglobulin levels did not improve significantly, but the Mayo clinical risk score improved significantly after long-term UDCA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)", "Forty-six patients with primary biliary cirrhosis from a single centre were studied in a randomized placebo-controlled trial to determine the effectiveness of ursodeoxycholic acid (UDCA) over a 2 year period. The two groups were well-matched at baseline. For each parameter, by calculating the difference between the median changes with time between the UDCA group and the placebo group, it was found that from entry, with respect to placebo, there were differences between median changes (MCD) favouring the UDCA group in bilirubin (MCD 5 mumol/L [95% confidence interval (CI) 1 to 12] at 1 year and 5 mumol/L (95% CI 1 to 9) at 2 years), alkaline phosphatase MCD 242 iu/L (95% CI 107 to 360) at 1 year and 268 iu/L (95% CI 146 to 424) at 2 years and aspartate aminotransferase MCD 26 iu/L (95% CI 12 to 41) at 1 year and 37 iu/L (95% CI 16 to 64) at 2 years. Within the UDCA group, there was long-term fall in alkaline phosphatase [median fall 116 iu/L (95% CI 93 to 378) at 2 years and aspartate aminotransferase [median fall 18 iu/L (95% CI 6 to 47) at 2 years; however, the major change in bilirubin was a modest rise over 2 years in the placebo group [median rise 2 mumol/L (95% CI 1 to 9)]. Changes in albumin, prothrombin ratio and immunoglobulins were generally minor and not significant.(ABSTRACT TRUNCATED AT 250 WORDS)", "One hundred fifty-one patients with primary biliary cirrhosis (PBC) grouped into four strata based on entry serum bilirubin ( < 2 mg/dL vs. 2 md/dL or greater) and liver histology (stages I, II vs. stages III, IV-Ludwig criteria) were randomized within each stratum to ursodiol or placebo given in a single dose of 10 to 12 mg/kg at bedtime for 2 years. Placebo- (n = 74) and ursodiol- treated (n = 77) patients were well matched at baseline for demographic and prognostic factors. Ursodiol induced major improvements in biochemical tests of the liver in strata 1 and 2 (entry bilirubin < 2), but had less effect on laboratory tests in patients with entry serum bilirubin of > or +2 (strata 3 and 4). Histology was favorably affected by ursodiol in patients in strata 1 and 2 but not in strata 3 and 4. Ursodiol enrichment in fasting bile obtained at the conclusion of the trail was approximately 40% and comparable in all strata. Thus, differences in ursodiol enrichment of the bile acid pool do not explain better responses of laboratory tests and histology found in patients with less advanced PBC. Patients treated will ursodiol tended to develop a treatment failure less frequently that those who received placebo, particularly in strata 1 and 2 (ursodiol 42%, placebo 60%, P = .078). Development of severe symptoms (fatigue/pruritus) and doubling of serum bilirubin were reduced significantly in ursodiol-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "The aim of this study was to evaluate whether ursodeoxycholic acid (UDCA) has any effect on the development of liver decompensation and on survival of patients with primary biliary cirrhosis (PBC).\n A total of 86 patients with compensated PBC were randomly assigned to receive UDCA (n = 43) or to remain untreated (controls, n = 43). There was no significant difference in the baseline characteristics between the two groups. Mean follow-up was 7.3 +/- 3.0 yr in the UDCA and 8.1 +/- 3.1 yr in the control group. Fourteen control patients were crossed-over to UDCA therapy after a median of 3.5 yr (range 2-8 yr), at their own request.\n Liver decompensation developed in 41 patients (22 in the UDCA and 19 in the control group) and liver death or transplantation in 33 (19 in the UDCA and 14 in the control group) patients. There was no significant difference in the probability of development of liver decompensation, liver death, or transplantation (by log-rank test) between UDCA-treated and control patients, whether by an intention-to-treat or by treatment-as-received analysis.\n UDCA was not found to have any demonstrable effect on the long-term outcome of PBC and did not improve the survival of PBC patients.", "Ursodeoxycholic acid (UDCA) and colchicine have beneficial effects in primary biliary cirrhosis (PBC). The efficacy of colchicine and UDCA in PBC was compared in a 2-year placebo-controlled study (n = 90).\n Clinical events, laboratory test results, and liver histology were recorded at the beginning and end of the trial.\n There were significantly fewer dropouts for hepatic reasons with UDCA than with placebo. Pruritus was reduced by both active drugs. Colchicine improved liver function test results only modestly, whereas UDCA significantly decreased the serum activities of aminotransferases, alkaline phosphatase, and gamma-glutamyltransferase compared with colchicine and placebo. Serum total bilirubin levels were decreased only by UDCA. Both colchicine and UDCA reduced serum cholesterol levels, and UDCA also reduced high-density lipoprotein cholesterol levels. Furthermore, UDCA reduced the serum levels of immunoglobulin (Ig) M and IgG, and colchicine reduced IgG levels compared with placebo. The elevated serum level of aminoterminal propeptide of type III procollagen remained unchanged by colchicine or UDCA, whereas the serum level of carboxyterminal propeptide of type I procollagen was significantly decreased by UDCA. UDCA significantly decreased ductular proliferation compared with colchicine or placebo.\n These data suggest that UDCA frequently is superior to colchicine and especially to placebo in the treatment of PBC.", "A multi-center double-blind controlled trial of ursodeoxycholic acid (UDCA) for treatment of primary biliary cirrhosis (PBC) was carried out. Twenty two and 23 patients were treated with 600 mg/day UDCA and placebo, respectively, for 24 weeks. In UDCA-treated patients, fall of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase activities started within 4 weeks after start of the trial and continued throughout the trial period. The serum IgM level fell in 7 UDCA-treated patients examined but not in 10 placebo-treated patients examined. Serum bilirubin concentration showed no significant change at the end of the study in either of UDCA- and placebo-treated group of patients. There was no significant difference between these two groups with respect to the frequency of improvement of pruritus. In UDCA-treated patients, serum bile acid composition changed markedly, though its concentration showed no significant change. The percentage of total bile acid which ursodeoxycholic acid took up increased, whereas those which cholic acid, chenodeoxycholic acid and deoxycholic acid took up were decreased.", "The aim of this study was to assess the efficacy of ursodeoxycholic acid (UDCA) for primary biliary cirrhosis in a randomized, double-blind placebo-controlled trial.\n Consecutive patients (n=192) were randomized to receive 14-16 mg UDCA/kg/day or placebo. Patients underwent a complete history, physical examination, liver chemistries, immunological determinations and liver biopsy at entry and at the end of the trial, which lasted for at least 2 years. Patients were seen every 3 months and the median follow-up was 3.4 years (range 0.3 to 6.1 years).\n Patients receiving UDCA (99) or placebo (93) were comparable with regard to age, sex, biochemical parameters and liver histology. UDCA treatment was associated with decreases in alkaline phosphatase, gammaglutamyl transferase, alanine aminotransferase, and cholesterol levels, effects which were conspicuous after 3 months of treatment and remained similar during the follow-up. During the study 31 patients (10 receiving UDCA and 21 placebo) discontinued the trial because of noncompliance (n=11), voluntary withdrawal (n=19) or adverse effects (n=1). Treatment failure (death or liver transplantation) was observed in 17 patients receiving UDCA and in 11 patients receiving placebo. Times to death or liver transplantation and to clinical complications were not significantly different in patients receiving UDCA or placebo. Histological analysis indicates that UDCA improved portal inflammation and prevented histological stage progression. By contrast, histological stage as well as ductular proliferation and ductopenia progressed in patients receiving placebo.\n Although UDCA treatment did not significantly affect time to death or liver transplantation and to clinical complications, the effects on both cholestasis and liver histology suggest that UDCA is safe and may be useful for preventing the progression of primary biliary cirrhosis.", "We studied the effect of ursodeoxycholic acid on 18 women and 2 men with primary biliary cirrhosis, mainly stages I and II. After a 3-mo observation period, patients were randomized to a 9-mo treatment period with ursodeoxycholic acid, 10 mg/kg.day, or placebo. Two patients on placebo left the study. In all patients on ursodeoxycholic acid, mean values of serum glutamate dehydrogenase, aspartate and alanine aminotransferases, alkaline phosphatase, and gamma-glutamyl transpeptidase fell significantly by 48%-79% after 18-24 wk; 7 of 10 showed a mean decrease of 35% in immunoglobulin M after 24 wk. Prothrombin time, serum bilirubin, albumin, the antipyrin breath test, and plasma disappearance of indocyanine green were normal initially and did not change. Total serum bile acid concentrations increased; ursodeoxycholic acid became the predominant bile acid. No significant improvement occurred in the placebo group. Hepatic histology improved in 6 patients of the ursodeoxycholic acid group but deteriorated in 4 patients receiving placebo. In studies with erythrocyte membranes, changes in electron spin resonance revealed that ursodeoxycholic acid was less toxic than chenodeoxycholic or deoxycholic acid, and coaddition of ursodeoxycholic acid prevented their toxic effect.", "Ursodeoxycholic acid (UDCA) has been shown to improve serum levels of liver enzymes and bilirubin in primary biliary cirrhosis (PBC). However, it is still uncertain whether UDCA treatment also improves symptoms, liver histology, and survival without liver transplantation.\n We randomized 116 patients with PBC to receive 0.5 g UDCA (n = 60) or placebo (n = 56) daily for 2 years. During the next 2 years, 80% of the UDCA-treated patients and 65% of the placebo-treated patients continued to take UDCA.\n UDCA improved serum enzyme values but not survival, symptoms, serum bilirubin levels, or liver histology. There was no significant difference in response between initially symptomatic and asymptomatic patients.\n UDCA in a dosage of 7.7 mg/kg body weight is of little benefit in PBC. This does not exclude the possibility that larger doses have beneficial effects.", "A double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) was conducted in 180 patients with primary biliary cirrhosis (PBC) to define the efficacy and safety of UDCA. Efficacy was assessed by time to treatment failure defined as death; liver transplantation; histological progression; development of varices, ascites, or encephalopathy; doubling of total serum bilirubin levels; progression of fatigue or pruritus; drug toxicity; or voluntary withdrawal.\n Patients with well-defined PBC underwent complete history, physical examination, liver chemistries, ultrasonography, upper endoscopy, and liver biopsy at entry as well as at 2 years. Liver chemistries were determined every 3 months.\n In patients receiving UDCA, treatment failure was delayed compared with the placebo-treated group (P = 0.0003, log rank test). Seven patients receiving UDCA died or required transplantation compared with 12 in the placebo group (P = 0.18). No patients discontinued UDCA because of side effects of toxicity.\n UDCA was extraordinarily safe and well tolerated, and its use was associated with delayed progression of the disease as defined in this study. However, the lack of effects on symptoms, histology, and the need for liver transplantation or survival indicate that further evaluation is necessary to determine the ultimate role of UDCA in the treatment of PBC.", "In primary biliary cirrhosis the hepatic lesions may result, at least in part, from the intracellular accumulation of potentially toxic endogenous bile acids. Preliminary work suggests that the administration of ursodiol (also called ursodeoxycholic acid), a hydrophilic bile acid without hepatotoxicity, leads to improvement in the condition of patients with primary biliary cirrhosis.\n We conducted a two-year, multicenter, double-blind trial to compare the efficacy of ursodiol with that of placebo. Patients with biopsy-proved primary biliary cirrhosis were randomly assigned to receive either ursodiol (13 to 15 mg per kilogram of body weight per day) (n = 73) or placebo (n = 73). Treatment failure was defined as a doubling of bilirubin levels to more than 70 mumol per liter or the occurrence of a severe complication (ascites or variceal bleeding) or an adverse reaction.\n Treatment failed in 6 patients in the ursodiol group, as compared with 13 in the placebo group (P less than 0.01 by Cox regression model). A single patient in each group withdrew because of minor adverse effects. After two years of treatment, the proportion of patients with clinically overt disease decreased only in the ursodiol group (P less than 0.02). The patients treated with ursodiol had significant improvements in serum levels of bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, cholesterol, and IgM (all P less than 0.001); the antimitochondrial-antibody titer (P less than 0.01); and the Mayo risk score (P less than 0.001). Follow-up analysis of 95 liver-biopsy specimens showed a significant improvement in the mean histologic score (P less than 0.002) and in all the characteristic histologic features except fibrosis only in the group given ursodiol.\n Ursodiol is a safe and effective treatment for primary biliary cirrhosis.", "The administration of ursodeoxycholic acid, a hydrophilic bile acid not hepatotoxic to humans, has been suggested for treatment of primary biliary cirrhosis to improve cholestasis and reduce hepatocellular damage. Efficacy of treatment has been studied mainly in patients with asymptomatic or early-stage disease. In January 1988, to establish the efficacy and safety of ursodeoxycholic acid in a population with more severe disease, we started a multicenter, double-blind, placebo-controlled trial in patients with symptomatic disease, that is, with pruritus or serum bilirubin exceeding 2 mg/dl. Forty-four patients were assigned to ursodeoxycholic acid, 500 mg daily (corresponding to about 8.7 mg/kg body weight in these patients), and 44 to a placebo. As planned at the beginning of the study, a preliminary analysis was performed when all patients had been followed for at least 6 months (33 patients up to 12 months). Pruritus, self-evaluated by the patients, and cholestyramine consumption, as recorded in a diary, decreased significantly (p < 0.01) in both groups. In patients who initially had abnormal levels, serum bilirubin decreased significantly (p < 0.05) in the ursodeoxycholic acid group compared to placebo. After 6 months the following were also significantly better in the ursodeoxycholic acid than in the placebo group: a composite weighted biochemical index taking into account the changes in serum bilirubin, alkaline phosphatase, gamma-GT and AST (p < 0.001); serum prealbumin (p < 0.05); IgG (p < 0.01) and IgM (p < 0.01) levels.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "1860198", "12823646", "2563096" ]

[ "Stroke Prevention in Atrial Fibrillation Study. Final results.", "Effects of low-dose warfarin and aspirin versus no treatment on stroke in a medium-risk patient population with atrial fibrillation.", "Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study." ]

[ "Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke.\n The Stroke Prevention in Atrial Fibrillation Study, a multicenter, randomized trial, compared 325 mg/day aspirin (double-blind) or warfarin with placebo for prevention of ischemic stroke and systemic embolism (primary events), and included 1,330 inpatients and outpatients with constant or intermittent atrial fibrillation. During a mean follow-up of 1.3 years, the rate of primary events in patients assigned to placebo was 6.3% per year and was reduced by 42% in those assigned to aspirin (3.6% per year; p = 0.02; 95% confidence interval, 9-63%). In the subgroup of warfarin-eligible patients (most less than 76 years old), warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67% (warfarin versus placebo, 2.3% versus 7.4% per year; p = 0.01; 95% confidence interval, 27-85%). Primary events or death were reduced 58% (p = 0.01) by warfarin and 32% (p = 0.02) by aspirin. The risk of significant bleeding was 1.5%, 1.4%, and 1.6% per year in patients assigned to warfarin, aspirin, and placebo, respectively.\n Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation. Because warfarin-eligible patients composed a subset of all aspirin-eligible patients, the magnitude of reduction in events by warfarin versus aspirin cannot be compared. Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin, and the trial is continuing to address this issue. Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke.", "To assess the optimal stroke prevention treatment for patients with atrial fibrillation (AF) and a low-medium risk (< or =4%) of stroke.\n A total of 668 patients with persistent or permanent AF, without an indication for full dose and with adequate rate control on sotalol, were randomized to warfarin 1.25 mg + aspirin 75 mg daily (W/A, 334 patients) or no anticoagulation (C, 334 patients). The mean follow-up period was 33 months. The protocol intended to verify a 37% relative risk reduction provided a 4% stroke incidence in the C group.\n The stroke incidence was less in the W/A group, although the reduction was not statistically significant (W/A 9.6% versus C 12.3%). Four haemorrhagic strokes were identified, two in each group. Secondary end-points were transient ischaemic attacks (TIA) (W/A 3.3% versus C 4.5%), all cause mortality (W/A 9.3% versus C 10.8%), cardiovascular morbidity (W/A 17.7% versus C 22.2%) and the combination of stroke + TIA (W/A 11.7% versus C 16.5%). Bleedings were documented in 19 versus four patients (W/A 5.7% versus C 1.2%) (P = 0.003), although none fatal. Sinus rhythm (SR) was recorded occasionally in 68 patients (W/A 9.6% versus C 10.8%). The stroke incidence tended to be higher in those with SR than without, 16.2% versus 10.4%.\n Our results were inconclusive, but consistent with a small beneficial effect of W/A for reduction of stroke and major vascular events in AF patients at moderate risk. The low-dose regiment produced, however, a significantly increased risk of bleedings. Documented SR occasionally recorded may represent a subpopulation that warrants full dose warfarin.", "From November, 1985, to June, 1988, 1007 outpatients with chronic non-rheumatic atrial fibrillation (AF) entered a randomised trial; 335 received anticoagulation with warfarin openly, and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo. Each patient was followed up for 2 years or until termination of the trial. The primary endpoint was a thromboembolic complication (stroke, transient cerebral ischaemic attack, or embolic complications to the viscera and extremities). The secondary endpoint was death. The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups, which did not differ significantly. 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo. 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo. Thus, anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF." ]

[ "8773035" ]

[ "A double blind placebo controlled trial of ginkgo biloba extract in acute cerebral ischaemia." ]

[ "A double blind placebo controlled trial was conducted in 55 patients of acute ischaemic stroke. Twenty one and twenty six patients were randomly allotted in group A and group B respectively. In group A, the patients received 40 mg Ginkgo biloba extract at 6 hourly intervals along with routine management. The placebo tablets were dispensed in the tablet form of same size, shape and colour and were given in the same way. After the patients were subjected to computerized tomographic (CT) scan to confirm acute ischaemic infarction, they were assessed on Mathew's scale and reassessed, at 2 weeks and 4 weeks of drug/placebo administration. Both groups showed significant improvement in Mathew's scale score after 2 weeks and 4 weeks. The difference in degree of change was negligible (p > 0.05) in either group. Estimation of relative changes of neurological deficit based on baseline values also showed negligible (p > 0.05) difference. A trial of Ginkgo biloba extract within 6 hours of stroke in a larger dose and in larger sample could be beneficial clinically in patients of cerebral ischaemic infarct, and needs further study. The usefulness of the plant extract has been demonstrated clinically and experimentally in more than 40 trials of chronic cerebral ischaemia, done elsewhere. This was not evident in our study as our study group was different (more than 48 hours after stroke). There appears to be no contraindication or adverse effect of this medication (Ginkgo biloba) in acute ischaemic stroke." ]

[ "13679494", "10543667", "11096321", "11328912", "8090335", "11271223", "16431893", "15882256", "11740389", "2510652", "2020357", "10954004", "9761517", "3527645", "17425758", "8434380", "8808232", "8382753", "17591533", "16421476", "10916115", "8639252", "7778179", "3291296", "12904684", "9446006", "2652496", "17097955", "7649579", "7970122", "7940807", "8438435", "12617335", "8430681", "11750440", "7652789", "8154037", "6089320", "1760541", "14616428", "12176568", "15502721", "11502994", "10069193", "1926395", "11959345", "17222813", "11274244", "10919587", "7843758", "10082500", "1539291" ]

[ "Amlodipine reduces cyclosporin-induced hyperuricaemia in hypertensive renal transplant recipients.", "Effect of nitrendipine on renal function in renal-transplant patients treated with cyclosporin: a randomised trial.", "Comparison of enalapril and losartan in the treatment of posttransplant erythrocytosis.", "The effect of ACE inhibitor and angiotensin II receptor antagonist therapy on serum uric acid levels and potassium homeostasis in hypertensive renal transplant recipients treated with CsA.", "Influence of diltiazem on renal function and rejection in renal allograft recipients receiving triple-drug immunosuppression: a randomized, double-blind, placebo-controlled study.", "Prophylactic isradipine treatment after kidney transplantation: a prospective double-blind placebo-controlled randomized trial.", "A randomized trial comparing losartan with amlodipine as initial therapy for hypertension in the early post-transplant period.", "ATR blockade reduces IFN-gamma production in lymphocytes in vivo and in vitro.", "Sustained improvement of renal graft function for two years in hypertensive renal transplant recipients treated with nifedipine as compared to lisinopril.", "[Effects of diltiazem on arterial pressure and renal function in renal transplanted and cyclosporin A treated subjects. Results after 3 months of a prospective study].", "Interaction between ciclosporin and diltiazem in renal transplant patients.", "Dihydropyridine calcium antagonists and renal function in hypertensive kidney transplant recipients.", "The effect of felodipine on renal function and blood pressure in cyclosporin-treated renal transplant recipients during the first three months after transplantation.", "[Protective effect of the calcium antagonist diltiazem on acute kidney failure following kidney transplantation. The results of a prospective randomized study].", "Enalapril/amlodipine combination in cyclosporine-treated renal transplant recipients: a prospective randomized trial.", "Diltiazem in renal allograft recipients receiving cyclosporine.", "A randomized placebo-controlled study of enalapril in the treatment of erythrocytosis after renal transplantation.", "Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants.", "ACE inhibitors and persistent left ventricular hypertrophy after renal transplantation: a randomized clinical trial.", "Randomized placebo-controlled study on the effects of losartan and carvedilol on albuminuria in renal transplant recipients.", "Regression of left ventricular hypertrophy by lisinopril after renal transplantation: role of ACE gene polymorphism.", "The beneficial effects of oral nifedipine on cyclosporin-treated renal transplant recipients--a randomised prospective study.", "Comparison of the effects of enalapril and theophylline on polycythemia after renal transplantation.", "Controlled trial of the protective effect of dihydroergotoxine (Hydergine) on cyclosporine-associated nephrotoxicity in renal graft recipients.", "Effect of angiotensin II receptor blocker on plasma levels of TGF-beta 1 and interstitial fibrosis in hypertensive kidney transplant patients.", "[Effect of diltiazem on concentration of cyclosporin metabolites in Sandimmune and Neoral treated kidney transplant patients].", "Calcium antagonist treatment of recipients minimizes early cyclosporine nephrotoxicity in renal transplantation: a prospective randomized trial.", "Efficacy and safety of valsartan, an angiotensin II receptor antagonist, in hypertension after renal transplantation: a randomized multicenter study.", "Comparison of perindopril and amlodipine in cyclosporine-treated renal allograft recipients.", "A double-blind, randomized, placebo-controlled study of nifedipine on early renal allograft function.", "Long-term protective effect of a calcium antagonist on renal function in hypertensive renal transplant patients on cyclosporine therapy: a 5-year prospective randomized study.", "Effect of nifedipine on renal haemodynamics and urinary protein excretion in stable renal transplant recipients.", "A prospective, randomized, open labeled crossover trial of fosinopril and theophylline in post renal transplant erythrocytosis.", "A controlled, double-blind, randomized trial of verapamil and cyclosporine in cadaver renal transplant patients.", "Is losartan as effective as enalapril on posttransplant persistent proteinuria?", "Usefulness and safety of treatment with captopril in posttransplant erythrocytosis.", "A preliminary report of diltiazem and ketoconazole. Their cyclosporine-sparing effect and impact on transplant outcome.", "Angiotensin I-converting enzyme inhibition after renal transplantation.", "Verapamil improves the outcome after cadaver renal transplantation.", "Diltiazem co-treatment in renal transplant patients receiving microemulsion cyclosporin.", "A randomized prospective double-blind placebo-controlled study of gallopamil, calcium antagonist of the verapamil type, in stable cyclosporine-treated renal transplant recipients.", "Calcium channel blockade and preservation of renal graft function in cyclosporine-treated recipients: a prospective randomized placebo-controlled 2-year study.", "Comparison of the effects of enalapril and losartan on posttransplantation erythrocytosis in renal transplant recipients: prospective randomized study.", "Renal effects of amlodipine in normotensive renal transplant recipients.", "Effect of diltiazem in the prevention of acute tubular necrosis, acute rejection, and cyclosporine levels.", "Double-blind, crossover, comparative study of doxazosin and enalapril in the treatment of hypertension in renal transplant patients under cyclosporine immunosuppression.", "Enalapril and losartan affect lipid peroxidation in renal transplant recipients with renin-angiotensin system polymorphisms.", "Effects of losartan and amlodipine on intrarenal hemodynamics and TGF-beta(1) plasma levels in a crossover trial in renal transplant recipients.", "Addition of isradipine (Lomir) results in a better renal function after kidney transplantation: a double-blind, randomized, placebo-controlled, multi-center study.", "Hypertension after renal transplantation. Calcium channel or converting enzyme blockade?", "ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients.", "Diltiazem treatment with reduced dose of cyclosporine in renal transplant recipients." ]

[ "Hypertension and hyperuricaemia are common side-effects of cyclosporin A (CsA) treatment in renal transplant recipients. While it is well established that the calcium channel blocker amlodipine can control CsA-induced hypertension effectively in this patient population, recent evidence suggests amlodipine might also reduce hyperuricaemia. The present study was designed to compare the effects of the calcium channel blocker amlodipine (5-10 mg/day) and the beta-adrenoceptor antagonist tertatolol (5-10 mg/day) on CsA-induced hyperuricaemia in post-renal transplant recipients with hypertension.\n Forty-eight hypertensive renal transplant recipients on a stable dose of CsA were randomized in a double-blind, parallel-group manner to receive either amlodipine (n = 24) or tertatolol (n = 24) for 60 days. The primary outcome measure was the change from baseline in serum uric acid concentration. Secondary analyses of efficacy were based on changes in renal function and blood pressure.\n Amlodipine significantly decreased serum uric acid levels from 483 +/- 99 to 431 +/- 110 microM/l (P < 0.001), while tertatolol significantly increased uric acid from 450 +/- 98 to 476 +/-84 microM/l (P = 0.006). Amlodipine also significantly increased glomerular filtration rate (P = 0.0048) and the clearance rate of uric acid (P = 0.023) and it reduced the fractional proximal tubular reabsorption of sodium (P < 0.001), compared with tertatolol. Renal plasma flow and filtered fraction were unaffected by both treatments, as was trough CsA blood concentration. Amlodipine lowered systolic blood pressure to a significantly greater extent than did tertatolol (P = 0.007). The time-dependent profile of diastolic blood pressure did not differ significantly between treatment groups. Both drugs were well tolerated.\n Amlodipine could be more appropriate than tertatolol for CsA-induced hypertension and hyperuricaemia in renal transplant recipients.", "Calcium antagonists such as nitrendipine reduce the effects of cyclosporin on renal haemodynamics, however, their long-term efficacy has not been established. We did a randomised trial to investigate the effects of nitrendipine on renal function in renal-transplant patients treated with cyclosporin.\n 253 renal-transplant patients were recruited: 52 normotensive patients (diastolic blood pressure <90 mm Hg) were assigned placebo and 57 nitrendipine 5 mg twice daily; 71 hypertensive patients (diastolic blood pressure >90 to <115 mm Hg) were assigned placebo and 73 nitrendipine 10 mg twice daily. Nitrendipine was increased to 20 mg twice daily if the target diastolic blood pressure (<90 mm Hg) was not achieved. The patients were seen once a month for 24 months; blood pressure and serum creatinine concentration were recorded at each visit. Analysis was by intention to treat.\n 63 patients were withdrawn (35 nitrendipine, 28 placebo). The mean serum creatinine concentration at baseline was slightly higher in the nitrendipine group (146.7 micromol/L [SE 4.42]) than in the placebo group (137.0 micromol/L [3.54]. At the 24-month endpoint or at dropout, serum creatinine concentration was significantly higher in the 123 patients in the placebo group than the 130 patients in the nitrendipine group (160.8 [7.1] vs 148.5 [5.3], p for effect of treatment=0.025, analysis of covariance in a two-way classification; 95% CI for difference -1.77 to -22.98). At study entry, the blood pressures of the placebo and the nitrendipine groups were almost identical. At 24 months, blood pressure was higher in the normotensive patients given a placebo than in those patients given nitrendipine. By contrast, blood-pressure values were similar in those hypertensive patients given a placebo and those given nitrendipine at the end of treatment.\n The calcium antagonist nitrendipine has no adverse effects on kidney function in renal-transplant patients with cyclosporin. The drug has a small but significant nephroprotective effect, that is independent of the drug's antihypertensive action.", "nan", "The angiotensin II (AT II) type I receptor antagonist losartan has been reported to increase urinary uric acid and potassium excretion. These effects might be beneficial in cyclosporin (CsA)-treated renal transplant recipients, who frequently suffer from hyperuricaemia and hyperkalaemia.\n In this prospective, open, randomized, two-way cross-over study we included 13 hypertensive CsA-treated patients after renal transplantation and administered either the angiotensin-converting enzyme (ACE) inhibitors enalapril or losartan. Laboratory parameters, 24-h urinary protein excretion, and mean 24-h arterial blood pressure (MAP) were checked after 3 weeks treatment with enalapril, after a wash-out period of 2 weeks, and before and after a 3-week treatment course with losartan.\n Both drugs slightly reduced MAP (losartan from 97+/-6 to 94+/-9 and enalapril to 93+/-8 mmHg). Serum potassium levels significantly increased during enalapril therapy (from 4.3+/-0.5 to 4.8+/-0.4 mmol/l, P<0.05), as did, although not significantly, uric acid concentrations (from 7.8+/-1.9 to 8.2+/-1.8 mg/dl, P=0.5). Losartan, on the contrary, only mildly affected serum potassium (4.3+/-0.5 vs 4.5+/-0.5 mmol/l, P=0.25) and serum uric acid decreased (from 7.8+/-2.4 to 7.3+/-1.8 mg/dl, P=0.6). Serum aldosterone and urinary aldosterone excretion were significantly reduced only during ACE inhibitor treatment, which might explain the variable effects on potassium homeostasis.\n Losartan may be a useful agent to reduce blood pressure and serum uric acid levels in renal transplant recipients treated with CSA: Furthermore, in this high-risk population, the effects on serum potassium levels are less marked with losartan than with enalapril.", "In a prospective, randomized and placebo-controlled study we evaluated the influence of treatment with the calcium-channel blocker diltiazem on the course and results of cadaveric kidney transplantation in 39 graft recipients. The grafts were reperfused with Euro-Collins solution containing diltiazem 20 mg/l. All recipients except those in chronic treatment with a calcium-channel blocker received preoperatively a bolus of diltiazem or placebo 0.3 mg/kg and in all an infusion of diltiazem or placebo 3 mg/kg/24 h was started preoperatively. After that, diltiazem or placebo was given orally for 3 months. Donors were not treated. Immunosuppressive therapy consisted of prednisone, azathioprine and CsA. There were no significant differences between the groups concerning donor or recipient characteristics, HLA-mismatching, and ischaemic time. Thrombosis leading to graft loss occurred in 3 recipients (diltiazem:2, placebo:1) and one graft was lost due to septicaemia (diltiazem). For the remaining 35 grafts no beneficial effect of treatment with diltiazem was found for the rate of delayed graft function, the rate of rejections, time to first rejection, whole blood CsA concentration, or graft function. The CsA dose needed to reach target whole blood concentration was significantly less in the diltiazem group. In conclusion, our results do not indicate any beneficial effects of treatment with diltiazem in cadaveric kidney transplantation, except a reduction of costs because of a significant reduction of the CsA dosage.", "There is evidence that calcium antagonists may have a beneficial effect on cyclosporine-induced nephropathy after transplantation. We treated 50 consecutive non-diabetic patients receiving their first cadaveric transplant with isradipine, a dihydropyridine calcium antagonist, or placebo in a double-blind, randomized, placebo-controlled trial. There were no significant differences between the two groups as regards age, weight, sex, HLA matching and ischaemic periods. To achieve optimal vasodilation, treatment was started intravenously 2 h before the transplantation procedure, and continued orally afterwards for 3 months. The immunosuppressive treatment included rabbit antithymocyte globulin on day 0, and oral cyclosporine from day 5. In both groups 7 patients had primary non-functioning grafts, but the incidence of never functioning kidneys due to vascular and thrombotic complications was significantly higher in the placebo group (0 vs 4 patients, P < 0.05). Hypertension was treated with oral labetolol in combination with guanfacine if necessary. In the placebo group antihypertensive medication had to be prescribed significantly more often (67% vs 33% of patients, P < 0.05), but resulted in similar blood pressure recordings in the two study groups. Cyclosporin A (CsA) plasma concentrations were also comparable but in the isradipine group a significantly higher dose of CsA was needed to achieve adequate levels (8.0 +/- 0.5 vs 6.2 +/- 0.5 mg/kg per day, P < 0.01). However, in the isradipine-treated patients creatinine clearance was significantly higher (66.1 +/- 4.5 vs 55.6 +/- 6.2 ml/min, P < 0.05) after 3 months. We conclude that isradipine is an effective antihypertensive agent after kidney transplantation. Isradipine ameliorates CsA-induced nephropathy and seems to protect against early postoperative vascular complications.", "Blockade of the renin-angiotensin-aldosterone system in the early post-transplant period remains controversial. Angiotensin II-receptor blockers (ARB) have many benefits to the patient with chronic kidney disease and these benefits may also apply to the renal transplant recipient (RTR). Additionally, there are theoretical benefits of ARB use in RTR. This study was designed to investigate the safety of early ARB use after renal transplantation.\n RTR with serum creatinine levels <3.0 mg/dl were randomized to receive either ARB (n = 29) or calcium-channel blocker (CCB; n = 27) as initial therapy for post-transplant hypertension. Differences in potassium, creatinine and haemoglobin concentrations were compared at baseline, 3, 6 and 12 months after transplantation.\n Withdrawal from the assigned treatment was high: 12 in the ARB group (due to hyperkalaemia in six) and 17 in the CCB group (due to intractable oedema in seven and post-transplant erythrocytosis requiring an angiotensin-converting enzyme inhibitor in seven). There were no differences in blood pressure, haemoglobin or creatinine concentration at any time-points. Mean potassium concentrations were only slightly higher in the ARB vs CCB group (range: 4.2-4.3 vs 3.7-3.8 mEq/l, respectively, but clinically significant) and the number of patients with potassium values >6.0 mEq/l was higher in ARB (n = 7) vs CCB (n = 1).\n These data suggest that hyperkalaemia is the major complication that occurs with the use of ARB in the immediate post-transplant period. ARB use does not affect renal function or complicate the post-transplant management of RTR. Other than reducing the incidence of post-transplant erythrocytosis, ARB use does not cause an excess incidence of anaemia. Strategies to reduce the risk of hyperkalaemia may allow increased use of ARB immediately after kidney transplantation.", "Type 1 angiotensin II (Ang II) receptor (AT(1)R) signaling induces proinflammatory responses. Recent studies suggest that T lymphocytes express AT(1)R; yet the effects of Ang II binding to AT(1)R on T cells are poorly understood. We examined the effect of AT(1)R blockade on release of the proinflammatory cytokine, interferon-gamma (IFN-gamma) by human lymphocytes in vivo and in vitro.\n We used an AT(1)R blocker losartan in a randomized clinical trial in kidney transplant recipients over a 12-month period [AT(1)R blocker (N= 11) and control (N= 10)]. Peripheral blood lymphocytes, isolated from both cohorts, were analyzed by enzyme-linked immunosorbent spot assays (ELISPOT) analyses and real-time reverse transcription-polymerase chain reaction (RT-PCR) to enumerate IFN-gamma producing T cells and IFN-gamma mRNA levels. The effects of AT(1)R blockade in vitro were assessed using human alloreactive T cells and an IFN-gamma producing human cytotoxic T-lymphocyte line. Alloreactive T cells were treated with losartan or candesartan and enzyme-linked immunosorbant assay (ELISA) was used to measure IFN-gamma protein release. The cytotoxic T-lymphocyte line also was AT(1)R blocker-treated prior to determining IFN-gamma producing cells by intracellular cytokine staining.\n The AT(1)R blocker cohort had a significant decrease in IFN-gamma producing peripheral blood lymphocytes (P< or = 0.05 for each time point) and IFN-gamma mRNA levels (P= 0.01 vs. control patients). Losartan also decreased IFN-gamma production (P < 0.001) in purified alloreactive T cells in vitro as did candesartan. Moreover, Ang II amplified IFN-gamma generation (P < 0.05) in alloreactive T cells while AT(1)R blocker treatment inhibited Ang II's effect (P < 0.04). AT(1)R blocker treatment furthermore also inhibited IFN-gamma production in the cytotoxic T-lymphocyte line.\n AT(1)R blockers may have a clinically relevant immunomodulatory role by blocking IFN-gamma production in T cells.", "Treatment of posttransplant hypertension is still a matter of debate. Calcium antagonists may ameliorate renal side effects of cyclosporin. Angiotensin converting enzyme- (ACE) inhibitors may be more effective in sustaining renal function in native chronic renal disease. We prospectively compared the effect of controlled release nifedipine and lisinopril on long-term renal function in hypertensive kidney transplant patients treated with cyclosporin.\n A total of 154 renal transplant patients presenting with hypertension (diastolic blood pressure >or=95 mmHg) during the first 3 weeks after transplantation were randomised to receive double-blind nifedipine 30 mg or lisinopril 10 mg once daily. A total of 123 patients completed 1 year of treatment (69 nifedipine, 54 lisinopril) and 64 patients completed 2 years of double-blind treatment (39 nifedipine, 25 lisinopril). Baseline glomerular filtration rate was measured as 99 mTc-diethylene-triaminepentaacetate clearance in a stable phase 2 to 5 weeks after inclusion and repeated at 1 and 2 years.\n Baseline glomerular filtration rates were similar (46+/-16 ml/min with nifedipine, 43+/-14 ml/min with lisinopril). The changes in glomerular filtration rates from baseline were statistically significant between the groups after 1 year (9.6 ml/min mean treatment difference (95% confidence interval [CI]s 5.5-13.7 ml/min, P=0.0001) and remained statistically significant also after 2 years (10.3 ml/min mean difference (95% CIs 4.0-16.6], P=0.0017). After 1 year glomerular filtration rates averaged 56+/-19 ml/min in the nifedipine group and 44+/-14 ml/min in the lisinopril group.\n Both nifedipine and lisinopril were safe and effective in treatment of hypertension in renal transplant patients treated with cyclosporin. Patients receiving nifedipine but not lisinopril improved kidney transplant function over a period of 2 years.", "With the aim to improve renal graft function and to prevent hypertension, we used the calcium-antagonist diltiazem in a prospective randomized study in 30 consecutive cadaveric renal transplanted patients from september 1987 to may 1988. The diltiazem (D+) group comprised 14 patients receiving a loading dose of 0.3 mg/kg followed by a 2 micrograms/kg/d continuous IV infusion of D started as soon as possible after clamp on renal artery removal. D was then given orally (120-180 mg/d) throughout the study. 16 patients without D composed the D- group. Cyclosporine A (csa) was started either just before transplantation (15 mg/kg/d orally) in 18 patients (9 D+ and 9 D-) or after 2-3 weeks of poly or monoclonal antibodies (5 D+ and 7 D- at 10 mg/kg/d. In addition to the usual monitoring, inulin (for GFR) and PAH (for ERBF), clearances were performed 7 days and 3 months after transplantation. If hypertension (blood pressure greater than 160/90 mm Hg) occurred, all but calcium-antagonists antihypertensive agents were used in both groups. Between D+ and D-, the number of patients requiring haemodialysis during the first week was not different (7/14 vs 5/16) like the number of dialysis session per patient (1.4 vs 1.1) day 7 GFR (19 +/- 22 vs 23 +/- 20) and day 7 ERBF (146 +/- 147 vs 226 +/- 224) ml/mn/1.73 m2; at 3 months 13/14 (93 p. 100) vs 12/15 (80 p. 100) of the grafts are functioning (NS), GFR (34 +/- 17 vs 33 +/- 10) and ERBF (242 +/- 90 vs 236 +/- 117) are not different.(ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "To investigate whether calcium antagonists are nephroprotective in hypertensive cyclosporine-treated renal allograft recipients.\n We studied 50 hypertensive and 17 normotensive renal transplants (eight females, nine males; 14-54 years, mean age 38.8 +/- 3.5 years). Hypertensive patients were randomized to be treated with (+Ca; 11 females, 13 males; 20-65 years, mean age 43.1 +/- 3 years) or without (-Ca; 15 females, 11 males; 25-60 years, mean age 41.3 +/- 2.5 years) a calcium antagonist (nitrendipine or nifedipine). Additional antihypertensives were given stepwise according to a standardized protocol: beta1-adrenoceptor blocker, diuretic alpha1-adrenoceptor blocker or vasodilator. Data were analysed at 0, 1, 2 and 3 years on an intention-to-treat basis.\n Hypertensive patients had a higher body mass index at 0/3 years (23.7 +/- 0.6/25.1 +/- 0.6 kg/m2) than normotensive patients (22.2 +/- 0.6/22.1 +/- 0.7 kg/m2). During the study, blood pressure in normotensive transplants was always slightly, but not significantly, lower than that of transplants with treated hypertension. There was no difference between the groups (+Ca) and (-Ca). Cr51-ethylenediaminetetracetic acid (EDTA) clearance (0/2 years) was 58 +/- 4/57 +/- 6 ml/min in normotensives, 52 +/- 4/47 +/- 4 ml/min in hypertensives (+Ca) and 47 +/- 4/49 +/- 6 ml/min in hypertensives (-Ca). Proteinuria (0/3 years) was 0.16 +/- 0.04/0.15 +/- 0.02 g/24 h in normotensive, 0.26 +/- 0.08/0.23 +/- 0.05 g/24 h in hypertensives (+Ca) and 0.26 +/- 0.07/0.22 +/- 0.05 g/24 h in hypertensives (-Ca).\n Post-transplant hypertension is associated with higher body mass index and poor renal function. No difference in the course of Cr51-EDTA clearance, serum creatinine, proteinuria or blood pressure was observed between groups treated with or without calcium antagonists. Calcium antagonists and conventional antihypertensive treatment have the same nephroprotective effect in hypertensive renal transplants, when treatment is started 3 months after transplantation.", "Due to their vasodilatory effect, calcium antagonist may have a renoprotective against cyclosporin (CsA)-induced nephrotoxicity and rise in blood pressure (BP) seen in renal transplantation.\n In order to evaluate the effect of the calcium antagonist felodipine on renal function and BP during cyclosporin treatment, 79 CsA-treated renal transplant recipients were investigated during the first 3 months after transplantation in a randomized, double-blind, placebo-controlled study with two parallel groups. Felodipine (ER tablets, 10 mg) or placebo was given prior to transplantation and each day during the study period. The patients were assessed twice, i.e. at 4-6 weeks and at 10-12 weeks after transplantation. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by constant infusion technique. Tubular function was estimated from clearance of lithium.\n At 6 weeks after transplantation, felodipine caused a significantly higher RPF [felodipine: 219 +/- 70 ml/min; placebo: 182+/-56 ml/min (mean+/-1 SD); P=0.03]. No differences were found in GFR, filtration fraction (FF), tubular sodium handling, or sodium excretion. Felodipine lowered BP significantly. At 12 weeks after transplantation, felodipine caused a significantly higher GFR (felodipine: 49+/-18 ml/min; placebo: 40+/-16 ml/min; P=0.05) and RPF (felodipine: 225+/-77 ml/min; placebo: 175+/-48 ml/min; P<0.01). No difference was found in FF. Felodipine lowered BP significantly. No differences were found with regard to duration of primary anuria, hospitalization time, number of rejection episodes, plasma creatinine day 7 post-transplant, or treatment doses of CsA.\n It is concluded that in renal transplant recipients treated with CsA, felodipine significantly increased both GFR and RPF 3 months after transplantation when compared with placebo, despite a concomitant lowering of BP. A possible antagonizing affect of felodipine against CsA-induced nephrotoxicity in these patients is suggested.", "In a prospective randomised study the effect of the calcium antagonist diltiazem on primary transplant failure following cadaver kidney transplantation was studied. The transplants were perfused with a solution containing 20 mg/l diltiazem, the graft recipient received diltiazem as a bolus injection of 0.28 mg/kg pre-operatively, followed by a continuous infusion of 0.0022 mg/kg X min for 48 hours. Thereafter diltiazem was applied orally (twice 60 mg/d). Glomerular filtration rate and renal blood flow were measured by single-shot techniques (inulin, PAH). For immunosuppression ciclosporin A and low-dose methylprednisolone were given. Nine patients (41%) in the control group (n = 22) but only two (10%) in the diltiazem group (n = 20) developed primary transplant failure (P less than 0.05). Glomerular filtration rate in transplants with primary function was significantly higher in the diltiazem group (day 4: 29 +/- 0.8 vs. 20 +/- 0.8; day 7: 39 +/- 1.4 vs. 24.9 +/- 0.7 ml/min, P less than 0.05) although ciclosporin blood levels were significantly higher in this group (week 1: 1150 vs. 728 ng/ml, P less than 0.01). The rate of rejection episodes was significantly higher in controls than in patients on diltiazem (0.5 +/- 0.05 vs. 0.1 +/- 0.02 rejection episodes per patient in the first postoperative month, P less than 0.05). Conclusion: Diltiazem has a protective effect against primary transplant failure following cadaver kidney transplantation. Furthermore, it might reduce the nephrotoxicity of ciclosporin A.", "Most hypertensive renal transplant recipients require two or more antihypertensive medications to achieve blood pressure control. However, which medications must be combined is still a matter of debate.\n A prospective randomized open-label blinded evaluation trial comparing the six-month effects of the amlodipine-enalapril combination (n = 32) vs. enalapril alone (n = 33) and vs. amlodipine alone (n = 34) on arterial pressure, renal function, albuminuria and tolerability.\n At six months, diastolic arterial pressure was more adequately controlled (i.e., <90 mmHg) in the combination group than in the amlodipine and enalapril groups (100% vs. 82.4% and 84.8%, respectively, p = 0.038). The same trend was observed for systolic arterial pressure (65.6% vs. 58.8% and 51.5%, NS). The six-month change in albuminuria was similar in the combination group and in the enalapril group (-64.7% vs. -59.5%); however, patients in the combination group exhibited a greater reduction in albuminuria than in the amlodipine group (-64.7% vs. -29.0%, p = 0.002). As compared with baseline values, serum creatinine and potassium remained unchanged in the combination group, whereas they increased by 9 +/- 12 micromol/L (p = 0.01) and by 0.2 +/- 0.4 mmol/L (p < 0.01), respectively, in the enalapril group. The cyclosporine trough levels remained unchanged in the combination group, but increased in the amlodipine group.\n Angiotensin-converting enzyme inhibitor (ACEI)-calcium-channel blocker (CCB) combination controls arterial pressure more adequately than ACEI alone or CCB alone, reduces albuminuria and may prevent the ACEI-induced initial rise in serum creatinine.", "Of 113 cyclosporine-treated primary renal allograft recipients, 60 were randomized to receive standard therapy without diltiazem (ND) and 53 received standard therapy plus diltiazem (D). There was no difference in CsA blood levels between ND and D at all intervals between 3 and 24 months follow-up, yet the D group required 35% less CsA than the ND group (measured at 12 months). At all intervals to 24 months there was no difference in blood pressure, renal function (as measured by serum creatinine), or in the number of grafts lost between the 2 groups (ND, 4 lost; D, 3 lost). There was no significant difference in the total number of rejection episodes in the 2 groups (ND, 89 episodes; D, 71 episodes). However, the severity of rejection episodes was greater in the ND group as evidenced by a significant difference in the usage of OKT3 (ND, 17 courses; D, 8 courses of OKT3, P < 0.05). Of the biopsy-proven episodes of rejection, there were more episodes of vascular rejection in the ND group (ND, 14 episodes; D, 3 episodes, P = 0.005). The incidence of primary nonfunction was less in the D group (ND, 16 patients; D, 5 patients, P = 0.05). It was concluded that the use of diltiazem was associated with a markedly reduced requirement for CsA without any adverse effect on graft function or graft outcome. Diltiazem with CsA was associated with fewer episodes of primary nonfunction and less-severe rejection episodes and in particular fewer episodes of vascular rejection.", "Erythrocytosis is a common complication of renal transplantation with an incidence of up to 17%. It is associated with an increased risk of complications due to thromboembolic events and has traditionally been treated by intermittent venesection. More recently, angiotensin-converting enzyme inhibitors have been shown to cause a fall in haematocrit in a number of groups of subjects and some uncontrolled studies have shown these drugs to be of possible therapeutic benefit in post renal transplant erythrocytosis.\n We performed a randomized double-blind placebo-controlled study in 25 patients with post-transplant erythrocytosis. Subjects received either 2.5 mg of enalapril daily or a placebo for 4 months and all patients completed the study period without any serious adverse effects.\n Haematocrit fell from 52.7 (+/- SEM 0.7) to 47.1 (+/- 1.8) at 1 month and 46.1 (+/- 1.2) after 4 months in patients receiving enalapril, with no change in the placebo group (P = 0.004). We did not demonstrate any change in serum erythropoietin in either group.\n Angiotensin-converting enzyme inhibitors are a safe and effective form of treatment for erythrocytosis developing after renal transplantation. The mechanism of action, however, is not mediated by changes in erythropoietin production and remains uncertain.", "The influence of antihypertensive treatment on the long-term evolution of arterial pressure and renal function was studied in a prospective controlled trial conducted in renal transplant recipients treated by cyclosporine. Within six months after transplantation, patients were randomly allocated to treatment by the angiotensin-converting enzyme inhibitor, lisinopril (ACEI, alone or associated with frusemide; N = 14), or the calcium antagonist, nifedipine (CA, alone or associated with atenolol; N = 11). Glomerular filtration rate (TcDTPA clearance) and effective renal plasma flow (hippuran clearance) as well as 24-hour urinary excretion of electrolytes and albumin were estimated at about 1 and 2.5 years of follow-up. Before initiation of antihypertensive therapy, the two groups were similar with regards to mean arterial pressure (119 +/- 2 vs. 120 +/- 4 mm Hg), effective renal plasma flow (285 +/- 26 vs. 248 +/- 33 ml/min/1.73 m2) and glomerular filtration rate (59 +/- 4 vs. 61 +/- 8 ml/min/1.73 m2 in the ACEI and CA groups, respectively). Both ACEI and CA treatments were associated with no change in renal function, a similar change in mean arterial pressure (ACEI -18 +/- 3; CA -13 +/- 5 mm Hg) and identical trough blood levels of cyclosporine. Urinary albumin excretion did not change significantly in any groups. Of interest, only in the ACEI group did filtration fraction significantly decrease (from 0.22 +/- 0.01% to 0.19 +/- 0.01% at final studies). These results indicate that in cyclosporine-treated transplant recipients, a satisfactory control of hypertension is obtained by chronic ACEI, which is as effective on arterial pressure as a combination of CA and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)", "Interventional studies of left ventricular hypertrophy (LVH) in renal transplant recipients are scarce and to date evaluated only patients immediately after renal transplantation.\n Randomized controlled trial that assessed the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in regressing persistent LVH after successful transplantation.\n 70 renal transplant recipients (47 men; age, 30 to 68 years) without diabetes previously randomly assigned to either cyclosporine or tacrolimus therapy, with LVH persisting 3 to 6 months after transplantation.\n Subjects were randomly assigned to either lisinopril (ACE-inhibitor group; 36 patients) or no therapy (control group; 34 subjects).\n Main outcome was change in left ventricular mass index (LVMi) at month 18.\n A consistent decrease in both systolic (SBP) and diastolic blood pressure (DBP) was observed in both groups (between-group differences, -1.7 +/- 3.3 mm Hg; 95% confidence interval [CI], -4.8 to 8.2; P = 0.6 for SBP; 0.3 +/- 2.2 mm Hg; 95% CI, -4.8 to 4.1; P = 0.9 for DBP), whereas LVMi regressed more in the ACE-inhibitor group (between-group difference, 10.1 +/- 16.3 g/m(2.7); 95% CI, 4.2 to 16.1; P < 0.01). A significant interaction of ACE inhibitors with cyclosporine in affecting LVMi change was shown by means of post hoc multiple regression analysis (P < 0.01; differences between cyclosporine and tacrolimus group, 13.3 +/- 3.9 g/m(2.7); 95% CI, 5.3 to 21.2; P < 0.01 in the ACE-inhibitor group; 3.7 +/- 4.2 g/m(2.7); 95% CI, -4.7 to 12.2; P = 0.4 in the control group).\n Single-center study with small sample size. Interaction of ACE inhibitors with cyclosporine treatment emerged from post hoc analysis.\n A prolonged course of ACE-inhibitor therapy is effective in regressing the persistent LVH of renal transplant recipients by mechanisms independent of effects on BP. This regression seems to be at least in part the effect of an interaction between ACE inhibitors and cyclosporine.", "The renoprotective effects of agents inhibiting the renin-angiotensin system in renal transplant recipients have been supposed but not finally proven. To shed more light on this issue, we performed a double-blind, placebo-controlled, crossover study to evaluate the influence of the AT-1 angiotensin II receptor blocker, losartan, on the surrogate marker of kidney injury, albuminuria, in patients after renal transplantation. The safety of this therapy was also evaluated.\n Fourteen of 16 patients (nine male, five female), age 45.36 +/- 3.04 years, 65.5 +/- 10.0 months after kidney transplantation, with hypertension and stable serum creatinine 123 +/- 4 micromol/L without proteinuria, completed the protocol. Each patient underwent two 8-week treatment periods (one with losartan 50-100 mg and one with carvedilol 12.5-25 mg) in random order, allowing an 8-week placebo washout between treatments. The target office trough blood pressure was below 130/85 mmHg.\n The ambulatory blood pressure did not differ in the treatment periods. Losartan significantly reduced albuminuria relative to placebo and carvedilol (27.62+/-17.58 vs. 49.55 +/- 25.33 v. 44.77 +/- 21.9 mg/g creatinine; P < 0.01). A significant but not clinically relevant decrease in hemoglobin level after losartan was observed (losartan: 129 +/- 3.1 g/l, placebo: 134.2 +/- 3.2, carvedilol: 137.1 +/- 3.7; P < 0.001). Serum potassium, creatinine, creatinine clearance, and trough blood cyclosporine levels were unaffected.\n Losartan decreases microalbuminuria in renal transplant recipients with clinically minimal side effects.", "Cardiac complications are the main cause of death in renal transplantation (RT), and left ventricular hypertrophy (LVH) may play an important role in these patients. The unfavorable genotype of the angiotensin-converting enzyme (ACE) gene has been associated with cardiovascular disease, including LVH. ACE inhibitors (ACEIs) reduce LVH, but little is known about the effects of ACEIs on LVH in RT patients with different insertion/deletion (I/D) genotypes of the ACE gene.\n We prospectively studied 57 stable nondiabetic RT patients with hypertension and echocardiographic LVH as well as a functional graft for 69.5 +/- 5.6 months. Patients randomly received either lisinopril 10 mg/day (group A, N = 29; 5 were excluded due to reversible acute renal failure) or placebo (group B, N = 28) for 12 months. Echocardiography (M-mode, 2-B, and color flow Doppler) was performed at baseline and 6 and 12 months later by the same examiner without previous knowledge of the genetic typing. The ACE genotype (I or D alleles) was ascertained by polymerase chain reaction (PCR; group A, DD = 10 and ID/II = 14; group B, DD = 15 and ID/II = 13).\n All patients maintained a good renal function (serum creatinine <2.5 mg/dL) during the follow-up and both groups received a similar proportion of antihypertensive drugs (beta-blockers 83 vs. 79%; Ca antagonists 66 vs. 68%; alpha1-adrenoreceptor antagonists 50 vs. 67%) during the study. As expected, mean arterial blood pressure and hemoglobin levels showed a higher percentage reduction in group A versus group B (-4 +/- 2.8 vs. 2.1 +/- 2.6%, P = 0.07, and -11.5 +/- 1.5 vs. -0.5 +/- 2.3%, P < 0.01, respectively). Group A patients showed a significantly higher decrement in LV mass index (LVMI) than group B at the end of follow-up, after adjusting for age, baseline LVMI, time after grafting and changes in systolic blood pressure, renal function, and hemoglobin levels (group A, -9.5 +/- 3.5% vs. group B, 3 +/- 3.2%, P < 0.05). As a result, 46% of group A and only 7% of group B patients showed a reduction of LVMI >/=15% (P < 0.01). The beneficial effect of lisinopril on LVMI reduction was more evident in DD patients (placebo DD, 8.4 +/- 4.1% vs. lisinopril DD, -7.2 +/- 5.3, P < 0.05), and a trend was observed in patients with other genotypes (placebo ID/II, 2.8 +/- 5.4% vs. lisinopril ID/II, -11.4 +/- 5%, P = 0.33).\n Lisinopril decreases LVM in renal transplant patients with hypertension and LVH, and the ACE gene polymorphism may predict the beneficial effect of this therapy. This finding may be important in targeting prophylactic interventions in this population.", "The aim of this study was to test the hypothesis that nifedipine will improve graft survival in cyclosporin A (CyA)-treated renal transplant recipients. One hundred and forty-seven patients were randomised to one of three regimens. Group A received CyA, 7 mg/kg per day, and prednisolone; group B followed the same regimen as group A plus oral nifedipine and group C received CyA, 4 mg/kg per day, prednisolone and azathioprine. Calcium channel blockers were avoided in groups A and C. The crude 2-year (P = 0.0223) and 4-year (P = 0.0181) graft survival was significantly better in group B (86% and 81%, respectively) than in group A (75% and 63%, respectively). Delayed initial function was seen least frequently in group B (10.2%) compared to groups A (31%) and C (28%; P < 0.01). Group B also experienced fewer rejection episodes than groups A and C (P < 0.05). We conclude that the combination of oral nifedipine and CyA significantly improves initial graft function, rejection frequency and long term graft survival.", "Posttransplant erythrocytosis (PTE) is a potentially serious complication for which (apart from phlebotomy) two alternative treatments have been proposed: theophylline (Theo) and angiotensin-converting enzyme inhibitors. We investigated 28 patients with PTE, who were assigned to 3 matched groups. Group 1 (10 patients) received 10 mg of Enalapril (Ena)/day. After 2 months, mean hematocrit (Ht) had dropped from 0.57 (range 0.52-0.62) to 0.45 (0.34-0.49). Ena was stopped and, after a period of 3.8 +/- 0.3 months, Ht had risen again to baseline values (0.56, range 0.52-0.61) in 8 of them. These 8 patients were then given 5 mg/day Ena. Ht decreased more slowly, and after 3 months reached a mean of 0.49 (0.44-0.54). Group 2 (9 patients) received 600 mg/day Theo in 2 doses. After 2 months, Ht had decreased from 0.56 (0.52-0.61) to 0.52 (0.46-0.63), but in 5 patients, Ht remained above 0.51. After 1 month discontinuation of treatment, PTE persisted in 7 patients. These patients were given 10 mg/day Ena, whereupon Ht decreased from 0.55 (0.52-0.64) to 0.46 (0.40-0.53) after 2 months and to 0.41 (0.33-0.47) after 3 months. Group 3 did not receive medical treatment. After 3 months, PTE persisted in 8 out of the 9 patients and remained unchanged during the following 3 months. Mean values for Ht were: baseline, 0.55 (0.52-0.58); after 3 months, 0.56 (0.53-0.59); and after 6 months, 0.55 (0.52-0.60). We conclude that Ena is superior to Theo in the treatment of PTE. There were no resistant patients, but individual sensitivity differs. Its effect is dose dependent, reversible, and reproducible. Excessive Ht decrease may occur; thus, doses should be titrated individually.", "nan", "Transforming growth factor-beta1 (TGF-beta 1) is involved in the pathogenesis of chronic allograft nephropathy after kidney transplantation. The aim of the study was to evaluate the effect of the angiotensin receptor blocker losartan on TGF-beta 1 plasma levels and proteinuria in hypertensive transplant recipients.\n A total of 162 transplant recipients were included in the study. The patients were randomized into 3 groups: group 1 received losartan; group II received an angiotensin-converting enzyme inhibitor (captopril), and group III received a calcium channel blocker (amlodipine). All the parameters were recorded at the time of therapy initiation and at 1, 4 and 12 weeks and 12 months thereafter. Graft biopsy before the start and at the end of the study was done to evaluate histopathological progression.\n Blood pressure was controlled in the 3 groups; however, the need for other antihypertensive agents was significant in groups I and II. Treatment with losartan significantly decreased the plasma level of TGF-beta1, 24-hour urinary protein and serum uric acid (p < 0.05). No significant changes were seen in the hemoglobin or serum potassium levels. The rate of histopathological progression was significantly lower in the losartan group. No patient was discharged from the study due to side effects.\n After transplantation all drugs were able to control blood pressure with good safety and tolerability. The study demonstrates that ARB significantly decreases the plasma levels of TGF-beta1, proteinuria and uric acid. These results could play an important and decisive role in the treatment and prevention of chronic allograft nephropathy.\n Copyright 2003 S. Karger AG, Basel", "Diltiazem reduces the cyclosporine dose required for blood levels in the therapeutic target range by 30 to 40%. The effect of diltiazem on the pharmacokinetic disposition of cyclosporine after oral Neoral application is unknown and it is unclear whether or not the diltiazem-cyclosporine interaction is affected by the galenic cyclosporine formulation.\n Fifty-one stable renal allograft patients (19 females, 32 males) were enrolled in this prospective, randomized and double-blind study. The patients were assigned to 3 treatment groups: with diltiazem (I, n = 17), with nifedipine (II, n = 17) and without calcium channel blockers (III, n = 17). Nine patients in each group received Sandimmun and 8 patients Neoral. Blood concentrations of cyclosporine and its metabolites AM1 and AM9 were measured using HPLC for 12 weeks. The 3 treatment groups were not different in respect to age, gender distribution and serum creatinine concentration. Cyclosporine doses were adjusted on basis of the blood levels.\n The cyclosporine doses required to achieve target blood levels were significantly lower in group I compared with group II (-43%) and group III (-33%; p < 0.0001). Although the cyclosporine blood concentrations in all groups were in the therapeutic range, the blood levels in group I showed a much lower variability. The blood concentrations of the metabolite AM1 in group I were significantly higher than those in groups II and III after dose correction (p < 0.0001), those of AM9 were significantly lower in group I than in groups II and III (p < 0.0001). The average dose, and the blood concentration of cyclosporine was not different when patients receiving Neoral were compared with those receiving Sandimmun within the groups. In the patients in group I, the blood concentration of metabolite AM1 was significantly higher after Sandimmun application than after Neoral. No other differences in the metabolite concentrations were detected within the groups comparing patients taking Sandimmun or Neoral. The incidences of acute rejection were lower in group I (17.6%) than in the other groups (II: 52.9%; III: 41%).\n Diltiazem significantly reduced the necessary dose of cyclosporine. Compared with groups II and III, the blood concentrations were more stable in patients in group I. Diltiazem increased the blood concentration of AM1 in patients treated with Sandimmun to a larger extent than in patients taking Neoral. No additional pharmacokinetic differences of the 2 cyclosporine applications different with Sandimmun or Neoral were found.", "nan", "The prevalence of posttransplant hypertension is high, and it appears to be a major risk factor for graft and patient survival. The aim of this study was to assess the efficacy and safety of valsartan, an angiotensin-receptor blocker (ARB), in the treatment of posttransplant hypertension.\n A multinational, multicenter, prospective, randomized, double-blind, placebo-controlled study was performed on the treatment of hypertension (systolic blood pressure [BP] >/= 140 and/or diastolic BP >/= 90 mm Hg) in adult cyclosporin-treated renal transplant recipients randomized to receive either valsartan (80 mg once daily) or a matching placebo for 8 weeks. After the first 4 weeks, furosemide 20 mg twice daily was added on a open basis if systolic BP remained >/= 130 mm Hg and/or diastolic BP remained >/= 85 mm Hg.\n One hundred fifteen (valsartan = 57, placebo = 58) uncontrolled hypertensive patients despite monotherapy for hypertension, other than angiotensin-converting enzyme inhibitor or ARB, were randomized. In the valsartan group, significant decreases were seen in systolic BP (from 153 +/- 11 to 140.9 +/- 18.35 mm Hg at 4 weeks, and 136.5 +/- 15 mm Hg at 8 weeks) and diastolic BP (from 93 +/- 9 to 85.2 +/- 11.28 mm Hg at 4 weeks, and 83.8 +/- 9.2 mm Hg at 8 weeks). There was no significant change in the placebo group. In the valsartan group, a statistically but not clinically significant reduction was observed in the mean hemoglobin concentration (12.9 +/- 1.6 g/dL versus 13.8 +/- 1.6 g/dL at 4 weeks, P < .01; and 12.3 +/- 1.6 versus 13.8 +/- 1.7 at 8 weeks; P < .001) as well as a significant increase in serum potassium (4.4 +/- 0.5 mmol/L versus 4.1 +/- 0.4 mmol/L at 4 weeks, P < .01) vs placebo.\n Valsartan is effective in the treatment of posttransplant hypertension and is well tolerated.", "The objective of this study was to compare the antihypertensive efficacy and influence on renal function of perindopril and amlodipine in cyclosporine-treated renal allograft recipients with mild to moderate hypertension. We conducted a randomized, double-blind, double-dummy crossover trial in ambulatory patients. Four phases were conducted: 2 weeks on placebo, 8 weeks of maintenance (perindopril or amlodipine), and 2 weeks of washout between treatment periods. Ten hypertensive patients with stable renal allograft function transplanted more than 6 months previously and receiving cyclosporine as part of their immunosuppressive regimen were studied. The patients were allocated to perindopril (2 or 4 mg/d) and amlodipine (5 mg/d) in a random sequence. If office diastolic pressure was greater than or equal to 90 mm Hg after 4 weeks, the dosage was doubled and continued for another 4 weeks. The main outcome measures were office and 24-hour ambulatory blood pressure changes after 8 weeks of active treatment and treatment and time effect on glomerular filtration rate and effective renal plasma flow. Perindopril and amlodipine were equally effective in lowering office blood pressure and similarly efficacious for the 24-hour period of the day. Neither drug affected glomerular filtration rate or effective renal plasma flow. Both agents demonstrated equivalent capacity (time x treatment, P = .955) to reverse renal vascular resistance (amlodipine from 0.35 +/- 0.02 to 0.30 +/- 0.02 mm Hg/mL per minute per 1.73 m2; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01) (time effect of all treatments together, P = .043).(ABSTRACT TRUNCATED AT 250 WORDS)", "A double-blind, randomized, placebo-controlled study was conducted to determine the effect of nifedipine on early renal allograft function when added to a triple therapy immunosuppression regime comprising low-dose cyclosporin (CsA), prednisolone and azathioprine. Fifty adult cadaveric renal allograft recipients were randomized to placebo (group P n = 17), nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 48 h, followed by matching placebo for 3 months (group NS n = 16) or nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 3 months (group NL n = 17). Donor and recipient exclusion criteria included recent calcium antagonist treatment. At 3 months after transplantation mean GFR adjusted for graft loss was significantly higher in group NL than in NS (mean +/- SD 61 +/- 28 versus 34 +/- 25 ml/min/1.73 m2; P < 0.05), group P being intermediate (45 +/- 34 ml/min/1.73 m2). Similarly, effective renal blood flow (ERBF) at 3 months was higher in group NL than in groups P and NS (mean +/- SD 351 +/- 175 versus 216 +/- 166 and 220 +/- 162 ml/min/1.73 m2; P < 0.05). The differences were not significant by 6 months post-transplantation. This study suggests that oral nifedipine commenced preoperatively and continued for 3 months following transplantation has beneficial effects on early renal allograft function when incorporated as part of an immunotherapy regimen based on cyclosporin.", "nan", "nan", "Angiotensin converting enzyme inhibitors (ACEI) and theophylline have been reported to decrease the elevated hemoglobin (Hgb) and hematocrit (Hct) levels in the renal transplant recipients with erythrocytosis. We conducted a prospective randomized, open labeled, crossover trial with theophylline, and an ACEI, fosinopril in nine stable renal transplant recipients with erythrocytosis. Aim of the study was to determine and compare the efficacy of these medications in stable renal transplant patients. At three months, compared to baseline, fosinopril significantly reduced the elevated hemoglobin (Hgb 17.2 +/- 0.6 vs. 14.9 +/- 1.4 gm/dL, p = 0.0023), and hematocrit levels (Hct 51.3 +/- 2.4 vs. 43.7 +/- 4.6%, p = 0.003). In contrast theophylline therapy was associated with a non-significant rise in hemoglobin (17.4 +/- 0.7 vs. 18.1 +/- 0.9gm/dL, p > 0.05) and hematocrit (52.4 +/- 2.7 vs. 54.7 +/- 3.9%, p > 0.05). With fosinopril compared to theophylline, there was a significant difference in the change in hemoglobin (baseline to three months 2.8 +/- 1.7 vs. -0.7 +/- 0.69 gm/dL respectively, p = 0.017), and the change in hematocrit (baseline to three months 9 +/- 6 vs. -2.3 +/- 2.7% respectively, p = 0.027). Four patients (44.4%) did not tolerate theophylline and did not complete the theophylline arm. To conclude, in our study, fosinopril effectively decreased the elevated hemoglobin and hematocrit in patients with post transplant erythrocytosis, and was superior to theophylline, while theophylline was ineffective and poorly tolerated in this condition.", "Calcium channel blockers have immunomodulating effects in vitro and may be effective in preventing cyclosporine nephrotoxicity. We studied the effect of verapamil following renal transplantation on the incidence of rejection and cyclosporine nephrotoxicity in a double-blind, placebo-controlled trial. Patients were randomly assigned to placebo (n = 28) or verapamil (n = 32) at doses of 80 mg twice a day. There was no difference in the incidence of rejection or cyclosporine toxicity in the two study arms. Recipients randomized to verapamil had lower mean cyclosporine doses at all intervals during a 1-year follow-up. Although cyclosporine doses were lower in the placebo group, the mean cyclosporine levels were equivalent in the two groups. Recipients in the verapamil-treated group had a higher mean serum creatinine at the end of the study--1.7 mg/dL versus 1.4 mg/dL in the placebo group. Actual 1-year graft survival was 89% for the placebo recipients versus 91% in the verapamil-treatment group. When compared with placebo, the concomitant use of low-dose verapamil results in lower cyclosporine doses but equivalent cyclosporine blood levels. Reduction in the incidence of rejection or cyclosporine nephrotoxicity were not observed.", "nan", "nan", "A prospective randomized trial was conducted to compare the effect of diltiazem (DILT) with ketoconazole (KETO) on sparing of cyclosporine dose and renal transplant outcome. Renal allograft recipients 18 years old and older were eligible for the study. Triple immunosuppression (TRIPLE) including prednisone, azathioprine, and CsA was administered to all patients. The maintenance CsA dose varied by study group. Patients were randomized to receive one of three treatment strategies: group 1-TRIPLE (CsA 8 mg/kg/day); group 2--TRIPLE (CsA 6 mg/kg/day) + DILT (60 mg b.i.d.); group 3--TRIPLE (CsA 3 mg/kg/day) + KETO (200 mg/day). Modification of the DILT dose was allowed as needed to effect blood pressure control in group 2 patients. Mean 1-month CsA dose reductions were 30% and 60% of controls in group 2 and 3, respectively. A continued effect over time was observed in patients administered KETO but not DILT. At 1 year patients taking KETO required an average of 77% less CsA than the average dose necessary to effect similar parent CsA blood levels when no enzyme inhibitor was used. The use of KETO and DILT for 1 year allowed for 53% and 14% reductions in CsA cost, respectively. These savings include the cost of the KETO or DILT. Serum creatinines, mean arterial pressure (MAP), and incidence of liver function abnormalities were similar throughout treatment groups. The rate of rejection, time to rejection onset, and survival (GS/PS) were not different among the groups. Fungal infections were fewer in patients treated with KETO (12%) than in controls (16%) and patients randomized to DILT (19%). KETO failed to prevent Aspergillus infection in one individual. The investigation failed to identify any harmful result of treating renal allograft recipients with either DILT or KETO for the purpose of reducing CsA expense.", "The angiotensin I-converting enzyme inhibitor captopril was administrated to 15 renal transplant patients for a minimum period of 14 weeks after transplantation. The object was to decrease ischaemic damage caused by secondary activation of the renal renin-angiotensin system after rejection and associated vascular damage. Captopril patients had lower s-creatinine values than controls in the immediate phase after rejection. On the other hand, after 14 weeks renal perfusion was better, but glomerular filtration rate lower in the captopril group than in the control group. However, none of the differences were significant. Renal function was examined during captopril administration, which may have affected the results. Final evaluation of this trial requires extended follow-up. Captopril was well tolerated in the low doses used (37.5-75 mg daily) in spite of varying degrees of renal failure and concomitant azathioprine administration. Only one case of mild leukopenia was recorded, which improved immediately after captopril interruption. No other serious side effects were observed. Captopril may be safely administered to renal transplant patients, if monitoring of renal function and possible side effects is carried through.", "Because of their favorable effects on renal hemodynamics, calcium antagonists may have a major role in the prevention and management of certain types of acute renal dysfunction. In fact, verapamil (VP) was shown to prevent cyclosporin A (CsA)-induced decreases in RBF in mice and in cadaver renal transplant (CRT) recipients. The study presented here of 59 cadaver renal transplant patients evaluates the outcome from perioperative treatment with VP (N = 30) administered intraoperatively into the renal artery (10 mg) followed by oral administration of 120 mg every 8 to 12 h for 14 days versus no drug (N = 29). Early immunosuppression included azathioprine, corticosteroids, and antilymphocyte globulin with subsequent overlapping with CsA on days 5 and 6. Actuarial graft survival at 1 yr was different when the two groups were compared (P less than 0.05). Estimated graft survival at 1 yr for VP patients was 93.3 compared with 72.4% in control patients. The improved graft survival was most striking in repeat transplants with 90% graft survival at 1 yr for VP recipients versus 37.5% for controls. Compared with controls, VP recipients had significantly improved renal parenchymal diastolic blood flow velocities on the first day after surgery (7.8 versus 5.8 cm/s). By day 7, GFR were greater with VP (44 +/- 29 mL/min) versus controls (28 +/- 22 mL/min). Of VP patients, 67% (18 of 24) had GFR greater than 30 mL/min versus 33% (9 of 26) for control patients. Similarly, on the seventh day, 77% (21 of 30) of VP patients had serum creatinines less than 2.0 mg% versus 34% (10 of 29) for controls.(ABSTRACT TRUNCATED AT 250 WORDS)", "Usage of cyclosporin (the Hong Kong Hospital Authority's single largest item of drug expenditure) continues to increase, mainly due to increasing numbers of renal allograft patients taking it as long-term antirejection therapy. Diltiazem, an antihypertensive agent, interferes with the first pass extraction of oral cyclosporin, thus serving to conserve its dosage.\n In renal transplant patients, to assess whether diltiazem co-treatment could achieve worthwhile dosage conservation of Neoral (a relatively new microemulsified cyclosporin formulation), safely.\n A randomized, placebo-controlled, double-blind clinical trial was undertaken at three local hospitals. Renal transplant recipients receiving Neoral as prophylactic immunosuppression were randomized to two treatment arms. Active treatment consisted of diltiazem tablets 30 or 60 mg twice daily for patients weighing < 60 or >or= 60 kg, respectively. One hundred and ten eligible patients gave their informed consent, and were followed up for at least six months. The mean difference in the dollar cost in the sixth month was the primary outcome. Secondary/ancillary outcomes included changes in cyclosporin dosage and blood level, and untoward clinical events including rejection. Outcomes were evaluated by intention to treat analyses.\n During weeks 23-26 (sixth month) post randomization, diltiazem co-treatment yielded an estimated average cost saving per patient on drugs of 15%[the 95% confidence interval (CI) of the difference being HK dollars 609 +/- 517 or pound 50 +/- 42], with no apparent excess of untoward or adverse events, complications, hospitalization, outpatient visits, or inferior quality of life.\n This diltiazem co-treatment regime applied to the nearly 1800 surviving renal allograft patients followed up in Hospital Authority hospitals could have saved approximately HK dollars 14.3 million ( pound 1.17 million) annually, without adverse sequelae.", "nan", "Studies have provided conflicting results as to the protective role of calcium channel blockers (CCB) in cyclosporine-treated patients with regard to blood pressure control and preservation of renal graft function. Lacidipine is a dihydropyridine CCB that possesses antioxidative, anti-atherosclerotic, and anti-adhesion properties and was shown to prevent cyclosporine-induced nephrotoxicity in a rat model.\n We conducted a multicenter prospective, randomized, placebo-controlled study in 131 de novo recipients of a cadaveric renal allograft on cyclosporine therapy. The aim of this 2-year study was to assess the effects of lacidipine on graft function (plasma iohexol clearance), renal plasma flow, anastomotic arterial blood flow, deterioration of renal function, blood pressure, acute rejection, and hospitalization rate.\n A total of 118 recipients were available for intention-to-treat analysis on efficacy (lacidipine: n=59; placebo: n=59). Graft function assessed by serum creatinine concentration and glomerular filtration rate measured as plasma iohexol clearance, was persistently better in lacidipine-treated patients from 1 year onwards (respectively, P<0.01 and P<0.05). Renal plasma flow and anastomotic blood flow were not significantly higher in lacidipine-treated patients. Three patients on lacidipine therapy and four on placebo experienced treatment failure defined as an increase in serum creatinine from baseline of more than 60% (log-rank test: P=0.57). Study groups did not differ in acute rejection rate, trough blood cyclosporine concentrations, blood pressure, number of antihypertensive drugs, hospitalization rate, and adverse event rate.\n The use of calcium channel blockers in cyclosporine-treated renal recipients results in a significantly better allograft function at 2 years and this effect is independent of blood pressure lowering.", "The aim of this prospective randomized study was to compare the safety and efficacy of enalapril (E) and losartan (L) in the treatment of posttransplantation erythrocytosis and the effect of the ACE genotype on response to therapy.\n Twenty-seven (24 male and 3 female, mean age 34+/-8 years) renal transplant recipients with erythrocytosis were treated either with E (15 patients) (10 mg/day) or L (12 patients) (50 mg/day) for 8 weeks.\n The hemoglobin levels were significantly decreased in the L (17.1+/-0.7 to 15.9+/-1.3 g/dl, P=0.01) and E groups (17.4+/-1.1 to 14.9+/-2.2 g/dl, P=0.001). Among the responders who discontinued treatment, there was a trend for longer time to relapse in the L group (7.38+/-3.75 months; 95% confidence interval: 0.03-14.7) compared with the E group (2.75+/-0.70 (95% confidence interval: 1.37-4.13) (P=0.11). Decrease in hemoglobin was more prominent with E compared with L (-3.26+/-0.65 vs. -1.70+/-0.39 g/dl, P=0.05). Decrease in hemoglobin levels between DD and non-DD genotype groups was similar (-2.0+/-1.5 vs. -1.7+/-2.3 g/dl, P=0.69).\n Enalapril caused a greater decrease but faster relapse in hemoglobin levels compared with losartan in patients with posttransplantation erythrocytosis. The DD type polymorphism had no effect on response.", "Renal effects of amlodipine in normotensive renal transplant recipients. The use of cyclosporin A (CsA) has improved the success of renal transplantation, but is associated with hypertension and significant renal toxicity. Previous reports suggest that calcium channel blockers may be useful in opposing the adverse effects of CsA. We have evaluated the effects of amlodipine (5 mg, once daily for 8 weeks) on renal function in 27 normotensive renal transplant recipients with stable renal function, in a double-blind, placebo-controlled, multicentre, cross over study. Amlodipine significantly reduced serum creatinine concentration relative to placebo (mean+/-SD: 168+/-65 vs 177+/-66 micromol/l; P=0.002) and there was a strong trend towards an increase in effective renal plasma flow on amlodipine relative to placebo (238+/-92 vs 217+/-87 ml/min; P=0.055). Glomerular filtration rate and lithium clearance were unaffected. Trough CsA blood concentration was unaffected. Amlodipine was well tolerated, with a low incidence of adverse events, and did not affect blood pressure or heart rate. In conclusion, amlodipine reduced serum creatinine in normotensive renal transplant recipients after only 8 weeks treatment, and was well tolerated in concomitant administration with CsA.", "nan", "nan", "In this study, the effect of enalapril (E) and/or losartan (L) on lipid peroxidation (LPO) is studied in renal transplant recipients (RTRs) with regard to polymorphisms of renin-angiotensin system (RAS).\n After determination of genotypes of the angiotensin-converting enzyme (ACE I/D), angiotensinogen (AGT M235T) and angiotensin II type 1 receptor (ATR1 A1166C) by PCR, sixty-four RTRs recruited to four groups randomly: first (13 patients) and second (20 patients) groups were treated with enalapril (E(+): 10 mg/day) and losartan (L(+): 50 mg/day) alone for 2 months, respectively. After 2 weeks as washout period, E group changed to L and vice versa as a cross-over design and they were treated for another 2 months. The third group (13 patients) as positive control received enalapril+losartan (E(+)L(+): 10 mg/day+50 mg/day) for 16 weeks, and the forth group (18 patients) as negative control received no medication (E(-)L(-)). Malondialdehyde (MDA) as LPO marker was measured before and after treatment. In this study, P<0.05 was considered significant.\n After 2 months of treatment, MDA level significantly decreased in all of the groups except the E(-)L(-). MDA level in pre- vs. post-intervention for the E(+)L(+), E(+), L(+) and E(-)L(-) groups were as follows: 5.81+/-2.13 nmol/mL vs. 1.61+/-0.80 nmol/mL (P=0.001), 5.10+/-2.05 nmol/mL vs. 1.68+/-1.01 nmol/mL (P=0.003), 5.20+/-1.61 nmol/mL vs. 1.22+/-0.27 nmol/mL (P=0.000) and 5.27+/-2.12 nmol/mL vs. 5.07+/-2.03 nmol/mL (P=0.52), respectively. Also, the same results were found in the end of 16th week. Although patients with DD genotype of ACE had higher MDA (P=0.01) levels, RAS polymorphisms could not predict the antioxidative response rate to the drugs (P>0.05).\n E and/or L reduce MDA regardless of the RAS genotypes.", "Hypertension and hyperfiltration are two important risk factors for the development of chronic allograft nephropathy. Transforming growth factor-beta(1) (TGF-beta(1)) is the main cytokine involved in the fibrotic process that is involved in chronic rejection. Angiotensin II upregulates TGF-beta(1) production. Angiotensin II receptor antagonists therefore could not only control BP but also reduce TGF-beta(1) production in renal transplant patients. The aim of this study was to compare the effects of losartan and amlodipine on renal hemodynamics, as well as TGF-beta(1) and endothelin-1 (ET-1) plasma levels in a group of renal transplant patients who had normal renal function and who were treated with cyclosporine. Seventeen renal transplant patients who were receiving cyclosporine and who had normal graft function were included in a random 2 x 2 crossover trial with amlodipine and losartan (6 wk with each therapy). Three studies were performed (at baseline and at the end of both treatment periods) to determine renal hemodynamics, TGF-beta(1), and ET-1. Both treatments controlled BP to a similar degree, but only amlodipine increased GFR through an increase in the estimated glomerular hydrostatic pressure and filtration fraction. In contrast, losartan maintained GFR and reduced estimated glomerular hydrostatic pressure and filtration fraction significantly. Losartan and amlodipine had opposite effects on TGF-beta(1). Amlodipine did not affect TGF-beta(1) concentrations. In contrast, losartan reduced the plasma levels of TGF-beta(1) by approximately by 50% (from baseline, 5.2 to 2.6 ng/ml; P: = 0.01); the majority of the patients reached normal levels of TGF-beta(1). ET-1 concentrations were significantly higher during amlodipine compared with losartan treatment. The present study documents that with similar control of BP, losartan and amlodipine have opposite effects on renal hemodynamics and on TGF-beta1 concentrations. These differences could be important for the management of chronic allograft nephropathy.", "After successful kidney transplantation patients may suffer from the adverse effects due to the use of calcineurin inhibitors. Calcium channel blockers are effective in the treatment of hypertension and may ameliorate cyclosporine- (CsA) induced impairment of renal function after kidney transplantation. Calcium channel blockers may also modulate the immune-system which may result in reduction of acute rejection episodes.\n From June 1995 till 1997 the effect of isradipine (Lomir) on renal function, incidence and severity of delayed graft function (DGF), and acute rejection after kidney transplantation, was studied in 210 renal transplant recipients, who were randomized to receive isradipine (n=98) or placebo (n=112) after renal transplantation in a double-blind fashion.\n In the isradipine group renal function was significantly better at 3 and 12 months (P=0.002 and P=0.021) compared with the placebo group. DGF was present in both groups: isradipine: (28+6)/98 (35%); placebo: (35+9)/112 (40%), P=0.57. Severity of DGF was comparable in both groups (isradipine: 9.1+/-8.7 vs. placebo: 9.3+/-8.1 days). No statistical difference was found in incidence or severity of biopsy-proven acute rejection [isradipine: (42+6)/98 (49%) versus placebo: (46+9)/112 (49%), P=1.00]. Renal vein thrombosis was observed in eight patients. This proved to be associated with the route of administration of the study medication [6/45 (13%) on i.v. medication versus 2/165 (1%) on oral medication, P<0.001].\n Addition of isradipine results in a better renal function after kidney transplantation, without effect on incidence or severity of DGF or acute rejection.", "We compared the effects of 4 weeks of calcium channel blockade (amlodipine) or converting enzyme inhibition (lisinopril) on blood pressure and renal hemodynamics in a double-blind crossover trial in a group of 20 hypertensive cyclosporine-treated renal transplant patients. Amlodipine (10 mg) was more effective than the same dose of lisinopril in controlling hypertension (mean 24-hour arterial pressure, 111 +/- 9 and 115 +/- 9 mm Hg, respectively; P < .05). Blood pressure during both treatments was lower than during placebo (124 +/- 12 mm Hg, P < .05). Compared with placebo, amlodipine treatment was associated with a significant increase in glomerular filtration rate (10 +/- 20%, P < .05) and effective renal plasma flow (27 +/- 20%, P < .01) and a decrease in renal vascular resistance (23 +/- 18%, P < .01). Renal hemodynamics did not change during lisinopril. Neither drug had an effect on proteinuria. The data indicate that amlodipine is more effective than lisinopril in controlling hypertension in cyclosporine-treated patients and that treatment with amlodipine but not with lisinopril is accompanied by an increase in glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance. The data suggest that the renin-angiotensin system does not play a main role in determining cyclosporine-associated changes in renal hemodynamics and has a limited role in determining cyclosporine-associated hypertension.", "Angiotensin-converting enzyme (ACE) inhibitors have been shown to slow the progression of chronic renal failure. However, the value of ACE inhibitors for the treatment of hypertension in renal allograft recipients has not been established. ACE inhibitors dilate the efferent glomerular arteriole, an effect that may aggravate the decrease in glomerular filtration rate resulting from cyclosporine-induced vasoconstriction at the afferent glomerular arteriole. Therefore, the goal of this double-blind, randomized study was to compare the antihypertensive and renal effects of the ACE inhibitor quinapril with those of the beta-blocker atenolol in renal allograft recipients in whom hypertension developed 6 to 12 weeks after transplantation. All patients received cyclosporine as an immunosuppressant and had stable graft function (serum creatinine concentration, <220 micromol/L) at entry into the study. Twenty-nine patients who received quinapril (daily dose titrated between 2.5 and 20 mg) and 30 patients who received atenolol (daily dose titrated between 12.5 and 100 mg) completed the 24-month study. The two groups did not differ in age, sex ratio, height, and weight before entry into the study. Quinapril decreased diastolic blood pressure from 96+/-1 to 84+/-1 mm Hg (average throughout treatment period), and atenolol decreased diastolic blood pressure from 96+/-1 to 83+/-1 mm Hg. The serum creatinine concentration did not change significantly in either group after 24 months (129+/-8 micromol/L at entry and 148+/-19 micromol/L after 24 months in the quinapril group and 131+/-6 micromol/L at entry and 152+/-15 micromol/L after 24 months in the atenolol group; P=NS for both groups). After 24 months, the change in urinary albumin excretion from baseline was -10+/-15 mg/d in the quinapril group and 52+/-32 mg/d in the atenolol group (P=0.03). These results show that quinapril and atenolol are effective antihypertensive drugs when used after renal transplantation. Moreover, compared with atenolol, quinapril has no adverse effects on graft function. The relative reduction in albuminuria observed with quinapril as compared with atenolol could indicate a beneficial effect of quinapril on long-term graft function.", "nan" ]

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[ "Efficacy of a 1-week, twice-daily regimen of terbinafine 1% cream in the treatment of interdigital tinea pedis. Results of placebo-controlled, double-blind, multicenter trials.", "A double-blind controlled trial of Whitfield's ointment and Variotin in ringworm infections with a two year \"follow-up\".", "Clinical evaluation of clotrimazole. A broad-spectrum antifungal agent.", "Efficacy and tolerability of terbinafine 1% topical solution used for 1 week compared with 4 weeks clotrimazole 1% topical solution in the treatment of interdigital tinea pedis: a randomized, double-blind, multi-centre, 8-week clinical trial.", "Comparison between undecylenic acid and tolnaftate in the treatment of tinea pedis.", "Comparison of an antifungal agent used alone with an antifungal used with a topical steroid in inflammatory tinea pedis.", "Treatment of toenail onychomycosis with 2% butenafine and 5% Melaleuca alternifolia (tea tree) oil in cream.", "Does naftifine have anti-inflammatory properties? A double-blind comparative study with 1% clotrimazole/1% hydrocortisone in clinically diagnosed fungal infection of the skin.", "Efficacy of undecylenic acid-zinc undecylenate powder in culture positive tinea pedis.", "A controlled study of haloprogin and tolnaftate in tinea pedis.", "Naftifine cream 1% versus clotrimazole cream 1% in the treatment of tinea pedis. Naftifine Podiatric Study Group.", "Comparative efficacy of naftifine, oxiconazole, and terbinafine in short-term treatment of tinea pedis.", "One week terbinafine 1% cream (Lamisil) once daily is effective in the treatment of interdigital tinea pedis: a vehicle controlled study. LAS-INT-06 Study Group.", "[Double blind trial of clotrimazole and econazole in tinea pedis (author's transl)].", "Treatment of interdigital tinea pedis with a 4-week once-daily regimen of butenafine hydrochloride 1% cream.", "Topical terbinafine and clotrimazole in interdigital tinea pedis: a multicenter comparison of cure and relapse rates with 1- and 4-week treatment regimens.", "A double-blind, vehicle-controlled study of the safety and efficacy of Fungoid Tincture in patients with distal subungual onychomycosis of the toes.", "[Terbinafine versus miconazole in patients with tinea pedis].", "Efficacy of tolciclate solution in patients with tinea pedis.", "[Naftifin in foot mycoses. Double-blind therapeutic comparison with clotrimazole].", "A randomized trial of acidified nitrite cream in the treatment of tinea pedis.", "[The antifungal agent naftifin. Placebo-controlled therapeutic comparison in tinea pedis].", "A clinical double-blind trial comparing amorolfine cream 0.5% (RO-14-4767) with bifonazole cream 1% in the treatment of dermatomycoses.", "One-week therapy with twice-daily butenafine 1% cream versus vehicle in the treatment of tinea pedis: a multicenter, double-blind trial.", "A comparative study of once daily bifonazole cream versus twice daily miconazole cream in the treatment of tinea pedis.", "Clinical comparison of the efficacy and tolerability of once daily Canesten with twice daily Nizoral (clotrimazole 1% cream vs. ketoconazole 2% cream) during a 28-day topical treatment of interdigital tinea pedis.", "[Antimycotic effect of naftifin in tinea pedis. Comparative double-blind study with bifonazole].", "Sulconazole nitrate 1% cream in the treatment of chronic moccasin-type tinea pedis caused by Trichophyton rubrum.", "Ciclopirox gel in the treatment of patients with interdigital tinea pedis.", "Efficacy of terbinafine 1% cream in the treatment of moccasin-type tinea pedis: results of placebo-controlled multicenter trials.", "Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis.", "Amorolfine in the treatment of onychomycoses and dermatomycoses (an overview).", "Topical clotrimazole in tinea pedis.", "Efficacy of miconazole in the topical treatment of tinea pedis in sportsmen.", "Double-blind study of the efficacy of 1 week topical terbinafine cream compared to 4 weeks miconazole cream in patients with tinea pedis.", "Tea tree oil in the treatment of tinea pedis.", "Treatment of chronic tinea pedis (athlete's foot type) with topical terbinafine.", "Determination of the subungual antifungal activity of amorolfine after 1 month's treatment in patients with onychomycosis: comparison of two nail lacquer formulations.", "Comparison of two topical preparations for the treatment of onychomycosis: Melaleuca alternifolia (tea tree) oil and clotrimazole.", "Efficacy of flutrimazole 1% powder in the treatment of tinea pedis.", "Short-duration therapy with terbinafine 1% cream in dermatophyte skin infections.", "Comparison of once- and twice-daily naftifine cream regimens with twice-daily clotrimazole in the treatment of tinea pedis.", "A clinical trial of topical terbinafine (a new allylamine antifungal) in the treatment of tinea pedis." ]

[ "Patients with tinea pedis often discontinue treatment before eradication of the fungus when their symptoms improve. The result is an incomplete cure/recurrence.\n Terbinafine, a topical fungicidal agent, was evaluated in double-blind, placebo-controlled trials (159 patients) for its ability to achieve cure and relief of symptoms in the same time frame, that is, before compliance wanes.\n Mycologic characteristics (with potassium hydroxide examination and culture) and clinical signs and symptoms were assessed at baseline, at the end of a 1-week, twice-daily treatment and at 1, 3, and 5 weeks after the completion of therapy.\n Both terbinafine and vehicle provided early relief of symptoms. However, only terbinafine gave progressive mycologic improvement such that at 5 weeks after treatment, 88% of the patients receiving terbinafine had converted from positive to negative mycology compared with 23% of the patients treated with vehicle.\n The rapid and potent fungicidal action of terbinafine results in a high cure rate in interdigital tinea pedis with 1 week of treatment and may avoid failures caused by non-compliance.", "nan", "The efficacy and safety of the broad-spectrum, topically applied antifungal agent clotrimazole were evaluated in two double-blind, multicentric trials. Ten investigators reported on a total of 1,361 cases in which a 1% solution or a 1% cream formulation was compared with its respective vehicle. Clotrimazole was therapeutically effective, as confirmed by mycological cure (negative microscopy and culture) and clinical improvement, in tinea pedis, tinea cruris, tinea corporis, pityriasis versicolor, and cutaneous candidasis. Furthermore, species identification established the efficacy of clotrimazole against Trichophyton rubrum, T mentagrophytes, Epidermophyton floccosum, Microsporum canis, Malassezia furfur (Pityrosporum orbiculare), and Candida albicans. Safety was demonstrated by the low incidence of possibly drug-related adverse experiences, namely, 19 (2.7%) of 699 patients who were treated with clotrimazole, of whom four (0.6%) discontinued treatment.", "In this double-blind clinical trial 429 patients (217 terbinafine and 212 clotrimazole) were randomized to receive twice daily terbinafine 1% topical solution for 1 week followed by a vehicle application for 3 weeks, or 1% clotrimazole solution for 4 weeks. Patients were evaluated clinically and mycologically at baseline and then at weeks one, two, four (end of treatment), and eight (end of follow-up). To be evaluable the patient needed to have a positive culture for a dermatophyte and positive KOH microscopy and a clinical diagnosis of tinea pedis (interdigital type) at baseline. Effective treatment of tinea pedis was recorded in 181 of 217 (83%) of patients treated for 1 week with terbinafine 1% solution and 174 of 212 (82%) of patients treated for 4 weeks with clotrimazole 1% solution. Mycological cure and disappearance of signs and symptoms were similar at each assessment visit in the two groups. In the subgroup of patients without any protocol violation the mycological cure rate was 95% (164 of 173) with terbinafine solution and 91% (159 of 174) with clotrimazole solution (P = 0.05). Adverse events believed to be drug-related occurred in 13 patients in the terbinafine group and 11 in the clotrimazole group (4 to 5% in each group). The events were primarily local skin reactions of mild to moderate intensity. It can be concluded that terbinafine 1% solution used for 1 week to treat tinea pedis is well tolerated and at least as effective as clotrimazole 1% solution used for 4 weeks.", "A double-blind parallel study comparing tolnaftate cream with undecylenic acid ointment and a placebo ointment in the treatment of symptomatic tinea pedis was conducted on the warm, humid Texas Gulf Coast. In one hundred and three patients studied, both the clinical and mycological effects of the two antifungal agents were indistinguishable. Both were significantly more effective than the placebo.", "The efficacy and safety of monotherapy with oxiconazole nitrate cream, 1 percent, a topical broadspectrum antifungal agent, were compared with those of combination therapy with oxiconazole nitrate cream, 1 percent, and fluticasone propionate cream, 0.05 percent, in a multicenter, randomized, double-blind, vehicle-controlled, parallel-group study of patients with inflammatory tinea pedis. Both combination therapy and monotherapy were associated with significantly greater proportions of mycologic and clinical cure, and a better global response than vehicle. An unexpected finding in this study was that more than 70 percent of patients with interdigital tinea pedis also had plantar or plantar plus vesiculobullous infection.", "The prevalence of onychomycosis, a superficial fungal infection that destroys the entire nail unit, is rising, with no satisfactory cure. The objective of this randomized, double-blind, placebo-controlled study was to examine the clinical efficacy and tolerability of 2% butenafine hydrochloride and 5% Melaleuca alternifolia oil incorporated in a cream to manage toenail onychomycosis in a cohort. Sixty outpatients (39 M, 21 F) aged 18-80 years (mean 29.6) with 6-36 months duration of disease were randomized to two groups (40 and 20), active and placebo. After 16 weeks, 80% of patients using medicated cream were cured, as opposed to none in the placebo group. Four patients in the active treatment group experienced subjective mild inflammation without discontinuing treatment. During follow-up, no relapse occurred in cured patients and no improvement was seen in medication-resistant and placebo participants.", "In a multicentre, double-blind, randomized, parallel group study in general practice, 269 patients with clinically diagnosed fungal infection of the skin were treated with either naftifine (Exoderil) or 1% clotrimazole plus 1% hydrocortisone (CHC; Canesten HC) applied twice daily for 4 weeks. Only 115 patients were shown subsequently to have a fungal infection by laboratory tests; the others had inflammatory disease of unknown aetiology. In those with fungal disease, both treatments were equally effective in terms of mycological cure (negative microscopy and culture). Clinical results for all 265 patients showed no clinically identifiable difference between the two preparations in terms of resolution of the disease, indicating that naftifine does have anti-inflammatory activity at least equal to CHC. This study suggests that there is no clinical advantage in treating patients with clinically diagnosed fungal infection of the skin with an antimycotic/corticosteroid combination as opposed to naftifine alone.", "One hundred fifty-one patients with tinea pedis participated in a double-blind study to assess the efficacy and safety of a powder containing undecylenic acid 2% and zinc undecylenate 20% versus a placebo powder. Patients were assigned to apply twice-daily applications of either active powder or placebo for a period of 4 weeks. Trichophyton rubrum or Trichophyton mentagrophytes were isolated from pretreatment cultures of 85 patients. Of these, 88% treated with active powder had negative cultures after 4 weeks compared with 17% of those treated with placebo powder (p less than 0.001). Fungus was identified in potassium hydroxide (KOH) treated skin scrapings of all 151 patients before treatment. Of those treated with active powder, 80% were KOH negative after 4 weeks compared with 49% of those treated with placebow powder (p = 0.001). Erythema and scaling were significantly improved by therapy with active powder, as were subjective evaluations of itching and burning. There were no side-effects or adverse reactions to undecylenic acid and its zinc salt.", "nan", "Fifty-seven subjects with tinea pedis applied naftifine cream 1% or clotrimazole cream 1% to affected areas twice daily for 4 to 6 weeks in a double-blind, randomized trial. Throughout the study, more naftifine-treated than clotrimazole-treated subjects were mycologically cured and globally improved, although differences were not statistically significant. Similar trends favoring naftifine were observed in the resolution of signs and symptoms. Treatment differences noted as early as week 2 suggest that naftifine may have a more rapid onset of action than clotrimazole.", "nan", "Duration of therapy is an important factor determining patients' compliance in dermatomycosis clinical practice. We undertook a prospective, randomised, double-blind, parallel group study to investigate the efficacy and tolerability of once daily treatment with terbinafine 1% cream for 1 week, compared to its vehicle, in adult patients with interdigital tinea pedis. Efficacy was assessed in terms of mycological cure, total clinical signs and symptoms scores, and clinical response, 1 day and 1, 5 and 7 weeks after end of treatment. Terbinafine 1% cream was significantly more effective than its vehicle in achieving and maintaining mycological cure for 7 weeks: 91.4% vs. 37.1%, P < 0.001. Terbinafine was also significantly more effective than its vehicle in reducing total clinical signs and symptoms scores, and in achieving clinical response. We conclude that terbinafine 1% cream, applied once daily for 7 days, is an effective and well-tolerated treatment for interdigital tinea pedis in nonimmunocompromised patients. The short duration of treatment needed to achieve mycological cure has important implications for patient compliance and for control of infection within the community.", "nan", "Butenafine hydrochloride, a potent new benzylamine with fungicidal activity, has been extensively studied and approved for topical use in Japan. Results reported here are from one of the first major North American butenafine clinical trials.\n We evaluated butenafine in the treatment of tinea pedis in a controlled, randomized, double-blind trial.\n Of 80 patients with positive fungal cultures, 40 applied butenafine 1% cream and 40 applied vehicle to the affected area once daily for 4 weeks. Efficacy was assessed during treatment and 4 weeks after.\n Significantly more patients using butenafine than using vehicle had mycologic cure (butenafine, 88%; vehicle, 33%) and effective clinical response (butenafine, 78%; vehicle, 35%). Differences between treatment groups were greatest (p < 0.001) 4 weeks after treatment.\n Butenafine applied once daily for 4 weeks resulted in an effective clinical response and mycologic cure of tinea pedis during treatment. Patients continued to improve for at least 4 weeks after treatment.", "nan", "Onychomycosis is one of the most common causes of nail disease and one of the hardest to treat among fungal infections. A double-blind, vehicle-controlled study has been conducted to evaluate the safety and efficacy of Fungoid Tincture (Pedinol Pharmacal, Inc), for the treatment of fungal infection of the toenails. Ten patients with distal subungual onychomycosis were treated for twelve months with topical Fungoid Tincture. Another ten patients with the same ailment were treated with the vehicle alone. Once a month, clinical and global evaluation of the target nail was done, in addition to trimming and debridement of the nails. After twelve months of treatment, 90 percent of patients applying Fungoid Tincture showed negative results on culture. There were minimal adverse effects.", "To compare the efficacy of terbinafine cream during 1 week with the efficacy of miconazole cream during 4 weeks in the treatment of tinea pedis.\n Prospective randomised double-blind study.\n Department of dermatology, Academic Hospital Leiden, the Netherlands.\n Patients who visited the general practitioner for tinea pedis and who had a positive KOH preparation were treated with terbinafine cream during 1 week and placebo during 3 weeks, or with miconazole cream during 4 weeks. Evaluation was done 1, 2, 3, 4 and 6 weeks after the start of the treatment. Mycological cure was defined as presence of a positive KOH preparation and a positive culture before treatment, and a negative result for both after treatment. Clinical efficacy was defined as mycological cure and presence of at most two minor symptoms (erythema, vesicles, squamae, itching) of the previously most serious skin lesion. Evaluation was done of all patients with a positive KOH preparation and of all patients with a positive KOH and a positive culture.\n 263 patients were included. Of these 207 had a positive culture; 56 patients had a positive KOH preparation but a negative culture. The group of patients treated with terbinafine and placebo consisted of 129 patients, the miconazole group of 134 patients. Both groups had an equal distribution as to age, sex, race, duration and seriousness of the fungal infection and previous treatment. Mycological cure and clinical efficacy throughout the evaluation were similar in both treatment groups, in both patients with positive KOH preparation and in patients with a positive KOH preparation and a positive culture. After 6 weeks mycological cure was seen in about 95% and clinical efficacy in about 87%.\n In the treatment of tinea pedis local application of terbinafine cream during 1 week is as good as treatment with miconazole cream during 4 weeks.", "Forty patients with tinea pedis were treated for six weeks in a double-blind study with a tolciclate or placebo solution. The tolciclate solution demonstrated moderate efficacy compared with placebo. The finding of positive KOH preparations in a significant number of tolciclate-treated patients with persistently negative cultures suggests that the vehicle used (polyethylene glycol-400) may not provide adequate penetration of this effective antifungal agent. No adverse effects were noted.", "nan", "Nitric oxide is continually released from normal skin and has antimicrobial effects. An acidified nitrite cream releases supraphysiologic concentrations of nitric oxide and is fungicidal in vitro.\n The purpose of this study was to assess the efficacy of an acidified nitrite cream as treatment for tinea pedis.\n Sixty patients were recruited with both a clinical diagnosis of tinea pedis and hyphae identified on direct microscopy; they were randomly placed into an active group treated with twice-daily application of a mixture of 3% salicylic acid in aqueous cream and 3% nitrite in aqueous cream for 4 weeks and a control group treated with 3% salicylic acid in aqueous cream and aqueous cream alone. Nineteen patients completed the trial in the active group and 16 patients in the control group. Mycologic cure (negative results on microscopy and culture) and clinical improvement were measured at 0, 2, and 4 weeks and after a 2-week interval with no treatment.\n At the end of the treatment period, 18 of the 19 patients in the active group were mycologically cured as were 11 of 16 in the control group (p = 0.042). Two weeks after the cessation of treatment, 13 of 19 patients in the active group were mycologically cured and 5 of 16 in the control group (p = 0.028). The initial clinical scores in the active and control groups were 8.1 and 8.19 (two-tailed p = 0.95). At 4 weeks they were 1.66 and 6.0 (two-tailed p = 0.002) and after 2 weeks with no treatment 1.45 and 7.4 (two-tailed p < 0.0002).\n Acidified nitrite is effective therapy for tinea pedis.", "The antimycotic efficacy of Naftifine was compared with that of placebo in a double-blind randomized trial in 60 patients with Tinea pedum proved by culture and microscopic examination. Naftifine was significantly superior to placebo concerning the number of mycologically cured patients as well as the clinical response to therapy. At the end of the study all patients were cured by Naftifine, whereas no patient of the placebo group showed an improvement.", "In a double-blind parallel study, 40 patients with dermatomycoses (one cutaneous candidosis and 39 dermatophyte infections) were treated topically with amorolfine (RO-14-4767) cream (0.5%), a new antifungal compound, or with bifonazole cream (1%). The treatment was applied once daily and was continued until 1 week after resolution of the symptoms, the maximum duration of treatment was limited to 6 weeks. Assessment of results was based on both clinical and mycological parameters. The percentages of amorolfine- and bifonazole-treated patients who were clinically and mycologically cured were 83.33% and 78.95%, respectively. Two patients treated with amorolfine and one patient treated with bifonazole were withdrawn from the trial because of side-effects. There was no significant difference between the two creams in clinical and mycological cure rates and tolerance.", "Butenafine hydrochloride, a benzylamine derivative with potent antifungal activity, has been used in Japan to treat superficial fungal diseases.\n We evaluated the safety and efficacy of twice-daily butenafine versus its vehicle in the treatment of interdigital tinea pedis in a multicenter, randomized, double-blind, parallel-group trial.\n A total of 402 patients with interdigital tinea pedis and a positive potassium hydroxide examination were enrolled. Of the 271 patients who had culture-confirmed tinea pedis and were assessed for efficacy, 132 applied butenafine and 139 applied vehicle twice daily for 1 week. Patients were assessed for mycologic cure, effective treatment, overall cure, and mycologic/clinical cure.\n The rates of all four end points were significantly higher with butenafine than with vehicle 5 weeks after treatment ended. Rates of mycologic cure and effective treatment with butenafine were significantly higher than with vehicle at cessation of treatment. Adverse events to treatment occurred in less than 1% of patients treated with butenafine and 2% of patients who applied vehicle.\n Butenafine applied twice daily for 1 week is highly effective in treating interdigital tinea pedis.", "nan", "The effects of two topical cream formulations containing clotrimazole 1% and ketoconazole 2%, respectively, were clinically compared in a double-blind, randomized manner for a 28-day therapy of interdigital tinea pedis in 106 treated patients. Ketoconazole was to be used twice daily whereas clotrimazole was administered only once daily. The primary response criterion defined as the number of patients with cure or improvement after 28 treatment days was comparable with 62.0% vs. 64.0% (clotrimazole vs. ketoconazole) for the full analysis set of 100 (50 vs. 50) patients. The mycological response revealed a negative culture and microscopy in 53.1% vs. 52.1% of the patients after 14, in 76.0% vs. 79.2% after 28, and in 83.7% vs. 76.9% after 56 days of observation, indicating a possibly better long-term efficacy of clotrimazole. The development of the overall score of tinea-related signs and symptoms did not show relevant differences between the two drugs and continuously decreased from 11+/-5 in both groups at baseline to 2+/-2 vs. 2+/-1 at day 56. As to the remission and improvement rates of single symptoms, better results were obtained under clotrimazole than under ketoconazole particularly for pruritus (97.8 vs. 89.6%) and burning/stinging (97.5 vs. 89.4%) which both are perceived as most bothersome by the patients. Furthermore, both substances appeared as comparably safe and well tolerable (8 vs. 7 adverse events with only 1 vs. 3 drug related). In conclusion, a successful therapy of tinea pedis can be achieved with both clotrimazole and ketoconazole within 28 days of treatment and once-daily clotrimazole is equally effective as twice-daily ketoconazole with favourable influences on the most irritating symptoms of the disease. Mycological and reliable clinical cure cannot be observed during two weeks after start of treatment.", "nan", "Sulconazole nitrate 1% cream applied twice daily was compared with its vehicle in the treatment of 229 patients with chronic moccasin-type tinea pedis confirmed by positive results of a potassium hydroxide preparation. At admission in this randomized, double-blind, parallel multicenter trial, 131 patients had positive dermatophyte cultures; Trichophyton rubrum was identified in 121 (92%). After 4 weeks of treatment, patients were examined and, if necessary, were treated for an additional 2 weeks. Sulconazole cream was significantly more effective than the vehicle in the treatment of chronic T. rubrum tinea pedis; 57% of patients were cured by sulconazole, compared with 13% cured with the vehicle. Relapse rates, assessed 2 weeks after the end of treatment, were significantly lower in patients treated with sulconazole than in those receiving vehicle (27% vs 71%). The 103 patients with moccasin-type tinea pedis whose cultures were not positive for T. rubrum achieved similar results.", "BACKGROUND Tinea pedis (athlete's foot) is the most common fungal infection in the general population. Ciclopirox, a broad-spectrum hydroxypyridone antifungal, has proven efficacy against the organisms commonly implicated in tinea pedis; Trichophyton rubrum, T.mentagrophytes and Epidermophyton floccosum.\n Two multicenter, double-blind, clinical studies compared the efficacy and safety of ciclopirox gel with that of its vehicle base in subjects with moderate interdigital tinea pedis with or without plantar involvement.\n Three hundred and seventy-four subjects were enrolled and randomized to one of two treatment groups: ciclopirox gel 0.77%, or ciclopirox gel vehicle, applied twice daily for 28 days, with a final visit up to day 50. The primary efficacy variable was Treatment Success defined as combined mycological cure and clinical improvement >/= 75%. Secondary measures of effectiveness were Global Clinical Response, Sign and Symptom Severity Scores, Mycological Evaluation (KOH examination and final culture result), Mycological Cure (negative KOH and negative final culture results) and Treatment Cure (combined clinical and mycological cure).\n At endpoint (final post-baseline visit), 60% of the ciclopirox subjects achieved treatment success compared to 6% of the vehicle subjects. At the same time point, 66% of ciclopirox subjects compared with 19% of vehicle subjects were either cleared or had excellent improvement. Pooled data showed that 85% of ciclopirox subjects were mycologically cured, compared to only 16% of vehicle subjects at day 43, 2 weeks post-treatment.\n Ciclopirox gel 0.77% applied twice daily for 4 weeks is an effective treatment of moderate interdigital tinea pedis due to T. rubrum, T. mentagrophytes and E. floccosum and is associated with a low incidence of minor adverse effects.", "nan", "Onychomycosis is a relatively common condition affecting toenails more than fingernails. It is caused predominantly by dermatophytes. Onychomycosis can cause pain and discomfort and has the potential to be a source of morbidity.\n We evaluated the efficacy and safety of ciclopirox nail lacquer solution 8% used to treat onychomycosis of the toe in the United States and in centers worldwide.\n Two identically designed, double-blind, vehicle controlled, parallel group multicenter studies were performed in the United States to evaluate the use of ciclopirox nail lacquer to treat mild to moderate toe onychomycosis caused by dermatophytes. In the first study, 223 patients were randomized to treatment (ciclopirox group: 112, vehicle group: 111), and in the second study, 237 subjects were randomized (ciclopirox group: 119, vehicle group: 118). Before randomization, patients were to have clinical features of onychomycosis in at least one great toe with positive light microscopic examination and a positive dermatophyte culture. The test material was applied daily for a period of 48 weeks to all toenails and affected fingernails, covering the entire nail plate and approximately 5 mm of surrounding skin. At baseline, subjects had between 20% to 65% area of target nail involved. Physician's assessments were carried out every 4 weeks, and mycologic evaluation and photographic planimetry using standardized photographs were performed every 12 weeks during the 48 weeks of treatment. In studies conducted outside the United States, patients were also to have clinical, microscopic, and culture evidence of onychomycosis. However, these studies included some patients infected with nondermatophyte organisms (eg, Candida species), and the area of nail involvement was generally greater than observed in the US studies. Treatment regimens also varied in the non-US studies with lacquer applications that were sometimes less frequent than the once daily treatment used in the US studies (eg, alternate day or twice weekly). In addition, the typical duration of treatment was 6 months in the non-US studies as compared with 48 weeks in the United States. Outcome measures were similar to those used in the US trials, although a non-photographic planimetric method was used to quantify disease extent.\n Data from the pivotal US trials have demonstrated that ciclopirox nail lacquer 8% topical solution is significantly more effective than placebo in the treatment of onychomycosis caused by Trichophyton rubrum, and of mild to moderate toe onychomycosis without lunula involvement. At the end of the 48-week treatment period, the mycologic cure rate (negative culture and negative light microscopy) in study I was 29% vs 11% in the ciclopirox and vehicle groups, respectively. Similarly, the mycologic cure rate for study II was 36% vs 9%, respectively. In the non-US studies, the mycologic cure rates ranged from 46.7% to 85.7%. In addition, ciclopirox nail lacquer has demonstrated a broad spectrum of activity with efficacy against Candida species and some nondermatophytes in non-US studies. Ciclopirox nail lacquer is considered extremely safe regarding causally related treatment emergent adverse-effects (TEAEs), with most TFAEs transient and localized to the site of action (eg, erythema and application site reaction). In the US studies, TFAEs were generally mild and cleared while the patient continued to use the nail lacquer.\n Studies conducted worldwide demonstrate the efficacy of ciclopirox nail lacquer for the treatment of finger and toe onychomycosis. Both controlled and open-label studies confirm the excellent safety profile of this topical therapy. Thus, the nail lacquer provides a treatment choice with a favorable benefit-to-risk ratio. With its novel mechanism of action and its topical route of administration, ciclopirox nail lacquer offers an innovative approach to the treatment of this often difficult-to-manage disease", "nan", "Clotrimazole is a new antifungal agent which is effective topically in dermatophytosis, cutaneous candidiasis, and tinea vesicolor. The authors performed a controlled double-blind clinical trial comparing topical clotrimazole with its vehicle in the treatment of 66 patients with dermatophytic infections of the skin of the feet. Clotrimazole proved to be effective in the treatment of tinea pedis of both the interdigital and the plantar hyperkeratotic types.", "A double-blind trial of 2% miconazole in a cream and in a powder base and of the respective vehicles was done in a group of forty-five young sportsmen regularly training and using the showers in a gymnasium. After 4 weeks treatment, the mycological cure rate using the active preparation was 60% compared to 24% for the placebo (P less than 0-05).", "To compare the efficacy of terbinafine cream for 1 week with the efficacy of miconazole cream for 4 weeks in the treatment of tinea pedis.\n Patients who visited our clinic for tinea pedis and who had positive KOH preparation and positive culture for dermatophyte were treated with terbinafine cream for 1 week and placebo for 3 weeks, or with miconazole cream for 4 weeks. Evaluation was done 1, 2, 3, 4 and 10 weeks after the start of the treatment. Mycological cure was defined as presence of a positive KOH preparation and a positive culture before treatment, and negative results for both after treatment. Clinical efficacy was defined as mycological cure and presence of at most a total signs and symptoms score of two.\n Forty-eight patients were studied. Half of them were treated with terbinafine and placebo and the other half with miconazole. Both groups had an equal distribution as to age, sex, race, duration and seriousness of the fungal infection and previous treatment. Mycological cure and clinical efficacy throughout the evaluation were similar in both treatment groups. After 10 weeks, mycological cure was seen in about 52.6 per cent and 55 per cent, and clinical efficacy in about 47 per cent, 45 per cent in terbinafine and miconazole treatment group respectively.\n In the treatment of tinea pedis local application of terbinafine cream for 1 week is as good as treatment with miconazole cream for 4 weeks.", "Tea tree oil (an essential oil derived primarily from the Australian native Melaleuca alternifolia) has been used as a topical antiseptic agent since the early part of this century for a wide variety of skin infections; however, to date, the evidence for its efficacy in fungal infections is still largely anecdotal. One hundred and four patients completed a randomized, double-blind trial to evaluate the efficacy of 10% w/w tea tree oil cream compared with 1% tolnaftate and placebo creams in the treatment of tinea pedis. Significantly more tolnaftate-treated patients (85%) than tea tree oil (30%) and placebo-treated patients (21%) showed conversion to negative culture at the end of therapy (p < 0.001); there was no statistically significant difference between tea tree oil and placebo groups. All three groups demonstrated improvement in clinical condition based on the four clinical parameters of scaling, inflammation, itching and burning. The tea tree oil group (24/37) and the tolnaftate group (19/33) showed significant improvement in clinical condition when compared to the placebo group (14/34; p = 0.022 and p = 0.018 respectively). Tea tree oil cream (10% w/w) appears to reduce the symptomatology of tinea pedis as effectively as tolnaftate 1% but is no more effective than placebo in achieving a mycological cure. This may be the basis for the popular use of tea tree oil in the treatment of tinea pedis.", "Twenty-seven patients with chronic tinea pedis, athlete's foot type, were enrolled in a randomized, double-blind trial of topical treatment with terbinafine 1% cream versus its vehicle (placebo). Patients were examined weekly during 4 weeks of twice-daily treatment and at follow-up 2 weeks after the conclusion of therapy. No adverse events were reported in either treatment group. Drug efficacy was evaluated in 22 patients, of whom nine (41%) were treated with terbinafine and 13 (59%) with placebo. Analysis of combined mycologic and clinical results showed that terbinafine was significantly more effective than placebo at the end of therapy (78% vs zero) and at the 2-week follow-up (89% vs zero) (p less than or equal to 0.001 at both intervals.", "nan", "The prevalence of onychomycosis, the most frequent cause of nail disease, ranges from 2% to 13%. Standard treatments include debridement, topical medications, and systemic therapies. This study assesses the efficacy and tolerability of topical application of 1% clotrimazole solution compared with that of 100% Melaleuca alternifolia (tea tree) oil for the treatment of toenail onychomycosis.\n A double-blind, multicenter, randomized controlled trial was performed at two primary care health and residency training centers and one private podiatrist's office. The participants included 117 patients with distal subungual onychomycosis proven by culture. Patients received twice-daily application of either 1% clotrimazole (CL) solution or 100% tea tree (TT) oil for 6 months. Debridement and clinical assessment were performed at 0, 1, 3, and 6 months. Cultures were obtained at 0 and 6 months. Each patient's subjective assessment was also obtained 3 months after the conclusion of therapy.\n The baseline characteristics of the treatment groups did not differ significantly. After 6 months of therapy, the two treatment groups were comparable based on culture cure (CL = 11%, TT = 18%) and clinical assessment documenting partial or full resolution (CL = 61%, TT = 60%). Three months later, about one half of each group reported continued improvement or resolution (CL = 55%; TT = 56%).\n All current therapies have high recurrence rates. Oral therapy has the added disadvantages of high cost and potentially serious adverse effects. Topical therapy, including the two preparations presented in this paper, provide improvement in nail appearance and symptomatology. The use of a topical preparation in conjunction with debridement is an appropriate initial treatment strategy.", "The aim of the study was to compare the efficacy and tolerability of flutrimazole 1% powder vs. bifonazole 1% powder in treating tinea pedis. A multicentre, double blind, randomized, parallel and comparative study was conducted. Two hundred and twenty-two patients with clinically and mycologically confirmed tinea pedis were randomized to flutrimazole (n = 136) or bifonazole (n = 138) 1% powder applied twice daily for 4 weeks. The corresponding clinical cure rates were assessed at 2 and 4 weeks of treatment, and the global (clinical and mycological) cure rates were determined at the fourth week. Clinical cure rates were 83.5 and 82.4% for flutrimazole and bifonazole, respectively (95% CI: -0.0806 to 0.1009). Global cure rates were observed in 65.3 and 70.1% of patients treated with flutrimazole and bifonazole, respectively (95% CI: -0.0828 to 0.1779). Three non serious adverse events at the application site--itching (one patient per group) and dishydrotic eczema (one patient treated with flutrimazole)--were recorded during the study. These results support that flutrimazol 1% powder applied twice daily for a duration of 4 weeks is highly effective in the treatment of tinea pedis, showing a similar therapeutic profile with that of bifonazole 1% powder.", "In a multicentre, double-blind, parallel-group study, the efficacy and safety of a single application of terbinafine 1% cream was compared with 3, 5 and 7 days' once-daily therapy in the treatment of tinea pedis and tinea corporis/cruris. Seventy-eight patients with tinea pedis (58 male, 20 female; mean age 36, range 19-80) and 21 patients with tinea corporis or tinea cruris (16 male, 5 female; mean age 37, range 22-72), presenting in general practice, were entered into the study. Of these, 65 patients with tinea pedis and 14 with tinea corporis or cruris completed the study and were evaluable. Twenty-eight days after commencing therapy 78, 83, 82 and 83% of patients with tinea pedis in the 1-, 3-, 5-, and 7-day treatment groups, respectively, were mycologically cured, and 61, 78, 71 and 67%, respectively, were 'effectively treated'. There was no statistically significant difference between treatment groups. Similarly high cure rates were seen in patients with tinea corporis and tinea cruris. Three months after commencing therapy there was little evidence of relapse. The study shows that there is a significant potential for short-duration therapy with terbinafine 1% cream in tinea infections of the skin, emphasized here by the high cure rates obtained following a single application.", "nan", "Twenty-three patients were enrolled in a randomized, double-blind trial of terbinafine 1% cream compared with placebo vehicle in the treatment of tinea pedis. Of the 20 patients who were evaluated for efficacy, 10 received terbinafine and 10 received placebo. Except for the terbinafine-treated patients being an average of 11 years older than the patients receiving placebo and the median duration of disease being 6 weeks longer in the placebo group, the two groups were demographically and clinically similar. Results of mycologic tests and clinical findings showed terbinafine to be significantly more effective than placebo in the treatment of tinea pedis. Significantly more terbinafine-treated patients than placebo-treated patients showed conversion to negative culture and microscopy at end of therapy and a significant reduction in scored signs and symptoms. Overall efficacy at follow-up (combined mycologic and clinical findings) was also significantly greater in the terbinafine group (78%) than in the placebo group (zero) (p less than 0.001). Unexplained elevation of liver function test results was noted in three placebo-treated patients and in one terbinafine-treated patient, but these changes were not considered clinically relevant or drug related." ]

[ "9609271" ]

[ "Low sodium diet and pregnancy-induced hypertension: a multi-centre randomised controlled trial." ]

[ "To examine the effectiveness of the standard policy in the Netherlands to prescribe a sodium restricted diet to prevent or to treat mild pregnancy-induced hypertension.\n Multi-centre randomised controlled trial between April 1992 and April 1994.\n Seven practices of independent midwives and one university hospital.\n The experimental group comprised 184 women given a low sodium diet (< or = 50 mmol sodium/day) and a control group of 177 women given a normal diet. Eligible women for inclusion had had a rise of blood pressure, or excessive weight gain or oedema during the antenatal period. The 361 women in the trial were recruited from 2020 nulliparae, of whom 1512 (75%) gave informed consent at the beginning of their pregnancy to participate in the study.\n The difference between highest diastolic blood pressure after randomisation and diastolic blood pressure at the moment of randomisation; referral and admission to hospital for hypertension.\n There was no difference in increase of diastolic blood pressure after randomisation, the percentage of referral and admission to hospital for hypertension, or in obstetric outcome between the two groups. Urinary sodium excretion after randomisation in the normal diet group was significantly higher than in the low sodium group.\n Prescribing a sodium-restricted diet to prevent or to treat mild pregnancy-induced hypertension is not effective. Therefore there is no need to introduce a salt restricted diet in prenatal care, although increasing evidence shows that a low sodium diet prevents hypertension in non-pregnant individuals." ]

[ "19211998", "16324343", "18070096", "17931979" ]

[ "Simvastatin inhibits the increase in serum tau protein levels in the acute phase of ischemic stroke.", "[Effects of atorvastatin on plasma hypersensitive C-reactive protein and interleukin-6 in patients with acute cerebral infarction].", "Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial.", "Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial." ]

[ "Our goal was to analyze the effects of treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (simvastatin, 40 mg/day) on serum S100BB and tau protein levels during the acute ischemic stroke (IS). Twenty four patients with IS were divided into two equal groups; treated and untreated with simvastatin. Blood was obtained four times during acute IS. Tau protein was noticed in six patients from treated group and in five patients from untreated group. The serum tau protein levels significantly increased on the 10th day only in patients untreated with simvastatin (p < 0.05). Simvastatin did not exert an effect on serum S100BB protein levels.", "To observe the effects of different doses of atorvastatin on the plasma hypersensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with acute cerebral infarction.\n 131 patients with acute cerebral infarction, 73 males and 58 females, aged 63 +/- 11, were randomly divided into 3 groups: Group A (n = 47), with basal treatment; Group B (n = 42), atorvastatin 10 mg was added every night; and Group C (n = 42), atorvastatin 20 mg was added every night. Before the treatment and 7 and 14 days after the treatment the plasma levels of hsCRP and IL-6, fasting plasma levels of lipid, such as total cholesterol (TC) and low density lipoprotein-C (LDL-C), liver functions, such as aspartate aminotransferase (ALT) and alanine transaminase (ALT), creatine kinase (CK), urea nitrogen, were detected. Neurological function deficit was determined. The survival condition was surveyed 6 months after.\n (1) The TC and LDL-C decreased after treatment in the 3 groups with significant differences between Group A and Group C, Group B and Group C, and Group B and Group C (all P < 0.05). (2) The plasma level of hsCRP decreased by 9.1%, 33.9%, and 30.1% respectively 7 days after treatment in Groups A, B, and C with significant differences between Groups A and B and between Groups A and C (both P < 0.05), however, without significant difference between Group B and Group C. The level of hsCRP decreased by 34.3%, 56.0%, and 52.9% respectively 14 days after treatment in the 3 groups with significant differences between Groups A and B and between Groups A and C (both P < 0.05), however, without significant difference between Group B and Group C. (3) The level of IL-6 decreased 7 and 14 days after treatment in all 3 groups, however, without significant differences between any 2 groups (all P > 0.05). (4) The decrease of hsCRP and decrease of IL-6 were not correlated with the percentage of TC decrease (both P > 0.05) in Group B. The decrease of hsCRP was not correlated with the changes of blood lipids in Group C. (5) Both the plasma hsCRP and IL-6 before treatment were positively correlated with the infection volume and neurological function score (all P < 0.01).\n Atorvastatin has an anti-inflammatory action benefiting the alleviation of secondary inflammatory damaged in acute cerebral infarction that is independent of lipid lowering.", "Although statins are being used for secondary prevention of ischemic stroke, recent experimental data have shown new pleiotropic effects of these drugs responsible for their role in neuroprotection. We conducted a pilot, double-blind, randomized, multicenter clinical trial to study for the first time safety and efficacy of simvastatin in the acute phase of ischemic stroke. Simvastatin/placebo was given at 3-12 h from symptom onset to 60 patients with cortical strokes. Efficacy on the evolution of several inflammation markers [interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, C-reactive protein, sApo/Fas, tumor necrosis factor-alpha, E-selectin, L-selectin and nitrites+nitrates] and neurological outcome was evaluated at baseline, day 1, 3, 5, 7 and 90. No differences were found amongst the biomarkers studied regarding treatment allocation. Although simvastatin patients improved significantly by the third day (46.4% vs. 17.9%, P = 0.022), a non-significant increase in mortality and greater proportion of infections (odds ratio 2.4, confidence interval 1.06-5.4) in the simvastatin group were the main safety concerns. Therefore, a larger clinical trial is needed to confirm the net benefit of this therapeutic approach.", "Patients with transient ischaemic attack (TIA) or minor stroke are at high immediate risk of stroke. The optimum early treatment options for these patients are not known.\n Within 24 h of symptom onset, we randomly assigned, in a factorial design, 392 patients with TIA or minor stroke to clopidogrel (300 mg loading dose then 75 mg daily; 198 patients) or placebo (194 patients), and simvastatin (40 mg daily; 199 patients) or placebo (193 patients). All patients were also given aspirin and were followed for 90 days. Descriptive analyses were done by intention to treat. The primary outcome was total stroke (ischaemic and haemorrhagic) within 90 days. Safety outcomes included haemorrhage related to clopidogrel and myositis related to simvastatin. This study is registered as an International Standard Randomised Controlled Trial (number 35624812) and with ClinicalTrials.gov (NCT00109382).\n The median time to stroke outcome was 1 day (range 0-62 days). The trial was stopped early due to a failure to recruit patients at the prespecified minimum enrolment rate because of increased use of statins. 14 (7.1%) patients on clopidogrel had a stroke within 90 days compared with 21 (10.8%) patients on placebo (risk ratio 0.7 [95% CI 0.3-1.2]; absolute risk reduction -3.8% [95% CI -9.4 to 1.9]; p=0.19). 21 (10.6%) patients on simvastatin had a stroke within 90 days compared with 14 (7.3%) patients on placebo (risk ratio 1.3 [0.7-2.4]; absolute risk increase 3.3% [-2.3 to 8.9]; p=0.25). The interaction between clopidogrel and simvastatin was not significant (p=0.64). Two patients on clopidogrel had intracranial haemorrhage compared with none on placebo (absolute risk increase 1.0% [-0.4 to 2.4]; p=0.5). There was no difference between groups for the simvastatin safety outcomes.\n Immediately after TIA or minor stroke, patients are at high risk of stroke, which might be reduced by using clopidogrel in addition to aspirin. The haemorrhagic risks of the combination of aspirin and clopidogrel do not seem to offset this potential benefit. We were unable to provide evidence of benefit of simvastatin in this setting. This aggressive prevention approach merits further study." ]

[ "16785475", "14614165", "12115176", "18055472", "16162882", "16935912", "16947384" ]

[ "Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial.", "Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig.", "Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion.", "Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate.", "Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition.", "Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial.", "Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: A one-year randomized, placebo-controlled study." ]

[ "The selective co-stimulation modulator abatacept demonstrated efficacy for treating rheumatoid arthritis in early clinical studies.\n To evaluate the effects of abatacept in patients with persistent, active rheumatoid arthritis despite methotrexate treatment.\n One-year, multicenter, randomized, double-blind, placebo-controlled trial (November 2002 to October 2004).\n 116 centers worldwide.\n 652 patients with active rheumatoid arthritis despite methotrexate treatment.\n Once-monthly infusion of a fixed dose of abatacept, approximately 10 mg/kg of body weight, or placebo.\n Co-primary end points were a 20% improvement in American College of Rheumatology (ACR) response criteria (ACR 20) at 6 months, clinically meaningful improvements in physical function, and change from baseline in joint erosion score at 1 year.\n Four hundred thirty-three and 219 patients were randomly assigned to abatacept or placebo, respectively, and 385 (89%) and 162 (74%), respectively, completed 1 year of treatment. In a modified intention-to-treat analysis, 6-month ACR 20, ACR 50, and ACR 70 responses were 67.9% for abatacept versus 39.7% for placebo (difference, 28.2 percentage points [95% CI, 19.8 to 36.7 percentage points]), 39.9% for abatacept versus 16.8% for placebo (difference, 23.0 percentage points [CI, 15.0 to 31.1 percentage points]), and 19.8% for abatacept versus 6.5% for placebo (difference, 13.3 percentage points [CI, 7.0 to 19.5 percentage points]), respectively. At 1 year, the responses increased to 73.1% for abatacept versus 39.7% for placebo (difference, 33.4 percentage points [CI, 25.1 to 41.7 percentage points]), 48.3% for abatacept versus 18.2% for placebo (difference, 30.1 percentage points [CI, 21.8 to 38.5 percentage points]), and 28.8% for abatacept versus 6.1% for placebo (difference, 22.7 percentage points [CI, 15.6 to 29.8 percentage points]), respectively (P < 0.001 for all). Physical function significantly improved in 63.7% versus 39.3% of patients (P < 0.001). At 1 year, abatacept statistically significantly slowed the progression of structural joint damage compared with placebo. Abatacept-treated patients had a similar incidence of adverse events (87.3% vs. 84.0%; difference, 3.3 percentage points [CI, -2.5 to 9.1 percentage points]) and a higher incidence of prespecified serious infections (2.5% vs. 0.9%; difference, 1.6 percentage points [CI, -0.3 to 3.6 percentage points]) and infusion reactions (acute, 8.8% vs. 4.1%; difference, 4.7 percentage points [CI, 0.9 to 8.4 percentage points]; peri-infusional, 24.5% vs. 16.9%; difference, 7.6 percentage points [CI, 1.2 to 14.0 percentage points]) compared with placebo recipients.\n The study involved only 1 group of patients over 1 year.\n Abatacept statistically significantly reduced disease activity in patients with rheumatoid arthritis and an inadequate response to methotrexate. Longer treatment in different patient populations is needed to establish its appropriate role in rheumatoid arthritis.", "Effective new therapies are needed for rheumatoid arthritis. Current therapies target the products of activated macrophages; however, T cells also have an important role in rheumatoid arthritis. A fusion protein--cytotoxic T-lymphocyte-associated antigen 4-IgG1 (CTLA4Ig)--is the first in a new class of drugs known as costimulation blockers being evaluated for the treatment of rheumatoid arthritis. CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells, blocking the engagement of CD28 on T cells and preventing T-cell activation. A preliminary study showed that CTLA4Ig may be effective for the treatment of rheumatoid arthritis.\n We randomly assigned patients with active rheumatoid arthritis despite methotrexate therapy to receive 2 mg of CTLA4Ig per kilogram of body weight (105 patients), 10 mg of CTLA4Ig per kilogram (115 patients), or placebo (119 patients) for six months. All patients also received methotrexate therapy during the study. The clinical response was assessed at six months with use of the criteria of the American College of Rheumatology (ACR), which define the response according to its extent: 20 percent (ACR 20), 50 percent (ACR 50), or 70 percent (ACR 70). Additional end points included measures of the health-related quality of life.\n Patients treated with 10 mg of CTLA4Ig per kilogram were more likely to have an ACR 20 than were patients who received placebo (60 percent vs. 35 percent, P<0.001). Significantly higher rates of ACR 50 and ACR 70 responses were seen in both CTLA4Ig groups than in the placebo group. The group given 10 mg of CTLA4Ig per kilogram had clinically meaningful and statistically significant improvements in all eight subscales of the Medical Outcomes 36-Item Short-Form General Health Survey. CTLA4Ig was well tolerated, with an overall safety profile similar to that of placebo.\n In patients with active rheumatoid arthritis who were receiving methotrexate, treatment with CTLA4Ig significantly improved the signs and symptoms of rheumatoid arthritis and the health-related quality of life. CTLA4Ig is a promising new therapy for rheumatoid arthritis.\n Copyright 2003 Massachusetts Medical Society", "T cells are involved in the pathogenesis of rheumatoid arthritis (RA). In animal models of autoimmune diseases, blockade of costimulatory molecules on antigen-presenting cells has been demonstrated to be effective in preventing or treating this disease by preventing T cell activation. To date, the effect of costimulatory blockade in patients with RA is unknown. The goal of this multicenter, multinational study was to determine the safety and preliminary efficacy of costimulatory blockade using CTLA-4Ig and LEA29Y in RA patients who have been treated unsuccessfully with at least 1 disease-modifying agent.\n CTLA-4Ig, LEA29Y (0.5, 2, or 10 mg/kg), or placebo was administered intravenously to 214 patients with RA. Patients received 4 infusions of study medication, on days 1, 15, 29, and 57, and were evaluated on day 85. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (ACR20). All patients were monitored for treatment safety and tolerability.\n CTLA-4Ig and LEA29Y infusions were well tolerated at all dose levels. Peri-infusional adverse events were carefully monitored, and showed similar incidence across all dose groups with the exception of headaches, which were slightly more frequent in the 2 treatment groups. The incidence of discontinuations due to worsening of RA was 19%, 12%, and 9% at 0.5, 2, and 10 mg/kg, respectively, in the CTLA-4Ig-treated patients and 3%, 3%, and 6% at 0.5, 2, and 10 mg/kg, respectively, in the LEA29Y-treated patients (versus 31% in the placebo group). ACR20 responses on day 85 had increased in a dose-dependent manner (23%, 44%, and 53% of CTLA-4Ig-treated patients and 34%, 45%, and 61% of LEA29Y-treated patients at 0.5, 2.0, and 10 mg/kg, respectively, versus 31% of placebo-treated patients).\n Both of the costimulatory blocking molecules studied were generally safe and well tolerated. As compared with placebo, both CTLA-4Ig and LEA29Y demonstrated efficacy in the treatment of RA.", "This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo. The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score (based on erythrocyte sedimentation rates; DAS28 (ESR)) for the abatacept vs placebo groups at day 197.\n Patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) were randomised 3:3:2 to abatacept ( approximately 10 mg/kg every 4 weeks, n = 156), infliximab (3 mg/kg every 8 weeks, n = 165), or placebo (every 4 weeks, n = 110) and background MTX. Safety and efficacy were assessed throughout the study.\n Similar patient demographics and clinical characteristics were present at baseline between groups, with mean scores of approximately 1.7 for HAQ-DI and 6.8 for DAS28 (ESR). At 6 months, mean changes in DAS28 (ESR) were significantly greater for abatacept vs placebo (-2.53 vs -1.48, p<0.001) and infliximab vs placebo (-2.25 vs -1.48, p<0.001). For abatacept vs infliximab treatment at day 365, reductions in the DAS28 (ESR) were -2.88 vs -2.25. At day 365, the following response rates were observed for abatacept and infliximab, respectively: American College of Rheumatology (ACR) 20, 72.4 and 55.8%; ACR 50, 45.5 and 36.4%; ACR 70, 26.3 and 20.6%; low disease activity score (LDAS), 35.3 and 22.4%; DAS28-defined remission, 18.7 and 12.2%; good European League Against Rheumatism (EULAR) responses, 32.0 and 18.5%; and Health Assessment Questionnaire Disability Index (HAQ-DI), 57.7 and 52.7%. Mean changes in physical component summary (PCS) were 9.5 and 7.6, and mental component summary (MCS) were 6.0 and 4.0, for abatacept and infliximab, respectively. Over 1 year, adverse events (AEs) (89.1 vs 93.3%), serious AEs (SAEs) (9.6 vs 18.2%), serious infections (1.9 vs 8.5%) and discontinuations due to AEs (3.2 vs 7.3%) and SAEs (2.6 vs 3.6%) were lower with abatacept than infliximab.\n In this study, abatacept and infliximab (3 mg/kg every 8 weeks) demonstrated similar efficacy. Overall, abatacept had a relatively more acceptable safety and tolerability profile, with fewer SAEs, serious infections, acute infusional events and discontinuations due to AEs than the infliximab group. Trial registration number: NCT00095147.", "A substantial number of patients with rheumatoid arthritis have an inadequate or unsustained response to tumor necrosis factor alpha (TNF-alpha) inhibitors. We conducted a randomized, double-blind, phase 3 trial to evaluate the efficacy and safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis and an inadequate response to at least three months of anti-TNF-alpha therapy.\n Patients with active rheumatoid arthritis and an inadequate response to anti-TNF-alpha therapy were randomly assigned in a 2:1 ratio to receive abatacept or placebo on days 1, 15, and 29 and every 28 days thereafter for 6 months, in addition to at least one disease-modifying antirheumatic drug. Patients discontinued anti-TNF-alpha therapy before randomization. The rates of American College of Rheumatology (ACR) 20 responses (indicating a clinical improvement of 20 percent or greater) and improvement in functional disability, as reflected by scores for the Health Assessment Questionnaire (HAQ) disability index, were assessed.\n After six months, the rates of ACR 20 responses were 50.4 percent in the abatacept group and 19.5 percent in the placebo group (P<0.001); the respective rates of ACR 50 and ACR 70 responses were also significantly higher in the abatacept group than in the placebo group (20.3 percent vs. 3.8 percent, P<0.001; and 10.2 percent vs. 1.5 percent, P=0.003). At six months, significantly more patients in the abatacept group than in the placebo group had a clinically meaningful improvement in physical function, as reflected by an improvement from baseline of at least 0.3 in the HAQ disability index (47.3 percent vs. 23.3 percent, P<0.001). The incidence of adverse events and peri-infusional adverse events was 79.5 percent and 5.0 percent, respectively, in the abatacept group and 71.4 percent and 3.0 percent, respectively, in the placebo group. The incidence of serious infections was 2.3 percent in each group.\n Abatacept produced significant clinical and functional benefits in patients who had had an inadequate response to anti-TNF-alpha therapy.\n Copyright 2005 Massachusetts Medical Society.", "To investigate the efficacy and safety of abatacept in combination with etanercept in patients with active rheumatoid arthritis during a 1-year, randomised, placebo-controlled, double-blind phase, followed by an open-label, long-term extension (LTE).\n Patients continued etanercept (25 mg twice weekly) and were randomised to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose of abatacept was established as 10 mg/kg in a separate trial, all patients received abatacept 10 mg/kg and etanercept during the LTE.\n A total of 121 patients were randomised; 80 completed double-blind treatment and entered the LTE. During double-blind treatment, the difference in the percentage of patients achieving the primary end point (modified American College of Rheumatology (ACR) 20 response at 6 months) was not significant between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in modified ACR responses were observed. Subsequent to the dosing change, similar modified ACR responses were seen during the LTE. Significant improvements in quality of life were observed with abatacept and etanercept versus placebo and etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept and etanercept-treated patients experienced serious adverse events (SAEs) at 1 year than patients receiving placebo and etanercept (16.5% v 2.8%), with 3.5% v 0% experiencing serious infections.\n The combination of abatacept (at a dose of 2 mg/kg during the double-blind phase and 10 mg/kg during the LTE) and etanercept was associated with an increase in SAEs, including serious infections, with limited clinical effect. On the basis of the limited efficacy findings and safety concerns, abatacept in combination with etanercept should not be used for rheumatoid arthritis treatment.", "To assess the safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis (RA) who had been receiving > or =1 traditional nonbiologic and/or biologic disease-modifying antirheumatic drugs (DMARDs) approved for the treatment of RA for at least 3 months prior to entry into the study.\n This was a 1-year, multicenter, randomized, double-blind, placebo-controlled trial. Patients were randomized 2:1 to receive abatacept at a fixed dose approximating 10 mg/kg by weight range, or placebo.\n The abatacept and placebo groups exhibited similar frequencies of adverse events (90% and 87%, respectively), serious adverse events (13% and 12%, respectively), and discontinuations due to adverse events (5% and 4%, respectively). Five patients (0.5%) in the abatacept group and 4 patients (0.8%) in the placebo group died during the study. Serious infections were more frequent in the abatacept group than in the placebo group (2.9% versus 1.9%). Fewer than 4% of patients in either group experienced a severe or very severe infection. The incidence of neoplasms was 3.5% in both groups. When evaluated according to background therapy, serious adverse events occurred more frequently in the subgroup receiving abatacept plus a biologic agent (22.3%) than in the other subgroups (11.7-12.5%).\n Abatacept in combination with synthetic DMARDs was well tolerated and improved physical function and physician- and patient-reported disease outcomes. However, abatacept in combination with biologic background therapies was associated with an increase in the rate of serious adverse events. Therefore, abatacept is not recommended for use in combination with biologic therapy." ]

[ "15878495", "17204317", "16032934", "17254760", "12324672", "11379810", "11266239", "18592826" ]

[ "Improvement of asthma control with beclomethasone extrafine aerosol compared to fluticasone and budesonide.", "Air trapping in mild and moderate asthma: effect of inhaled corticosteroids.", "Hydrofluoroalkane-134A beclomethasone or chlorofluorocarbon fluticasone: effect on small airways in poorly controlled asthma.", "Beclometasone dipropionate extrafine aerosol versus fluticasone propionate in children with asthma.", "Airway and systemic effects of hydrofluoroalkane fluticasone and beclomethasone in patients with asthma.", "A randomized, double-blind comparison of beclomethasone dipropionate extrafine aerosol and fluticasone propionate.", "Efficacy of HFA-beclomethasone dipropionate extra-fine aerosol (800 microg day(-1)) versus HFA-fluticasone propionate (1000 microg day(-1)) in patients with asthma.", "Comparison of the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler on exhaled inflammatory markers in childhood asthma." ]

[ "Qvar Autohaler efficacy on asthma control, assessed with E. Juniper asthma control questionnaire (ACQ), was compared with fluticasone and budesonide. An open randomized study, stratified (2:1) on the intake of long-acting beta2-mimetics (LAbeta2), was performed in patients with moderate to severe poorly controlled asthma (defined by at least one nocturnal discomfort in the last 5 days or a mean of 2 puffs of short-acting beta2-mimetics in the last 7 days or exercise dyspnea) despite treatment with beclomethasone < or = 1000 microg/day (or equivalent). 460 patients received Qvar Autohaler 800 microg/day (n = 149), fluticasone Diskus 1000 microg/day (n = 149) or budesonide Turbuhaler 1600 microg/day (n = 162) during 12 weeks. Asthma control improved in all groups, with no difference between groups. For patients treated with LAbeta2 (n = 286) a significantly greater improvement of the ACQ score was obtained with Qvar Autohaler versus fluticasone (1.0 +/- 1.0 vs. 0.6 +/- 0.9; P = 0.019), but not versus budesonide (0.9 +/- 0.9). Pulmonary function test improvements were similar in the 3 groups. The significant improvement in asthma control in patients receiving LAbeta2 suggests potential advantages for extrafine aerosols as part of anti-inflammatory treatment optimization.", "Air trapping reflects small airway obstruction in asthma and can be assessed quantitatively by high-resolution computed tomography (HRCT). Hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) is deposited across all sizes of airways, including the small ones. However, its long-term effect on air trapping remains unknown in uncontrolled asthma.\n To compare the effect of inhaled corticosteroids of different particle size - HFA-BDP and fluticasone propionate (FP) - on lung attenuation in mild-to-moderate uncontrolled asthma.\n A randomized study was performed to analyze the effect of HFA-BDP (400 microg/d) or FP (500 microg/d) given over a period of 3 months to patients with uncontrolled mild-to-moderate asthma. HRCT was performed with spirometric gating, and lung attenuation was measured at residual volume and at pulmonary total capacity. The difference between inspiratory and expiratory attenuation was calculated as an air trapping index.\n Twenty-five out of 58 patients had abnormal air trapping and could be included in the study. Lung attenuation significantly diminished in the posterior zones of the lung after a 3-month treatment with HFA-BDP or FP, but the difference between the groups was not significant. Adjusted mean variations of the air trapping index from baseline to treatment completion were 34.3 (11.2, 57.3) and 27.3 (6.4, 48.2) for the HFA-BDP and FP groups, respectively. However, the reduction of air trapping area was more pronounced in the group treated with HFA-BDP.\n Inhaled corticosteroids decrease air trapping in uncontrolled asthma regardless of their particle size.\n In mild-to-moderate asthma, air trapping assessed by HRCT may be a new outcome related to the control of the disease.", "Inflammation in asthma extends into the small airways (< 2 mm diameter). Most inhaled corticosteroids are suspensions with a particle size > 2 mm. Therefore, inflammation in the small airways of patients with asthma may not be adequately treated with these preparations. Some inhaled corticosteroids, on the other hand, are compounded with alcohol, resulting in a solution producing an aerosol that has a mean particle diameter of < 2 mm. This study was designed to compare the addition of equivalent amounts of two inhaled corticosteroids (one a suspension and one a solution) to the treatment of patients with asthma, which was uncontrolled despite treatment with moderate to high doses of inhaled corticosteroids and usually additional controller medications. The study was performed with 30 patients, > or = 18 years of age. Subjects were randomized in a single-blind fashion to receive, in addition to their current asthma therapy, either CFC-FP 220 microg each morning and 110 microg each evening (n = 10) or HFA-BDP 160 mcg twice daily (n = 20). Pre- and postbronchodilator spirometry, single breath nitrogen washout for closing volume and residual volume by plethysmography were assessed before and after 3 months of therapy. In the subjects who received HFA-BDP, the ratio of closing volume (CV) to vital capacity (VC) and residual volume (RV) decreased significantly (p = 0.0214 and 0.0433, respectively), whereas forced expiratory flow over 25-75% of the vital capacity (FEF25-75%), forced expiratory volume in 1 second (FEV1), and morning peak flow improved significantly (p = 0.0014, 0.0184, and 0.0321). Improvements from baseline of CV, CV/VC, and postbronchodilator FEF25-75%, were statistically significant in the HFA-BDP group compared with the CFC-FP group (p = 0.0049, 0.0194, and 0.0355, respectively). These preliminary findings suggest that the addition of HFA-BDP, compared with CFC-FP in patients with poorly controlled asthma despite receiving moderate to high doses of inhaled steroids, has a greater effect on parameters reflecting small airway patency presumably secondary to reduction in inflammation.", "Beclometasone dipropionate (BDP) extrafine is a hydrofluoroalkane-based, chlorofluorocarbon (CFC)-free inhalation aerosol. This study was conducted to determine whether BDP extrafine and CFC-fluticasone proprionate (FP) aerosols were equivalent in terms of efficacy and tolerability in children with symptomatic mild-to-moderate asthma. Male and female patients (aged 5-12 yr) with an asthma diagnosis for > or =3 months, peak expiratory flow (PEF) > or =60% of predicted normal and suboptimal asthma control were randomised to double-blind treatment with BDP extrafine 200 microg day(-1) (n=139) or CFC-FP 200 microg day(-1) (n=141) for up to 18 weeks. After 6 and 12 weeks, study medication was 'stepped down' to 100 and 50 microg day(-1), respectively, if patients had achieved good asthma control. Patients with poor asthma control discontinued from the study and those with intermediate control continued in the study but did not undergo a dose reduction. The estimated treatment difference in morning PEF% predicted at 6 weeks was -1.9% (90% CI -4.9, 1.0). There was a trend towards a greater increase in forced vital capacity (% predicted) in the BDP extrafine group (5.3 versus 0.4%; p=0.084). A 'step-down' in therapy to 100 microg day(-1) was possible in 36% and 42% of patients in the BDP extrafine and CFC-FP groups, respectively, at 6 weeks. Both drugs were well tolerated. BDP extrafine and CFC-FP aerosols were equally effective at improving asthma control in children with mild-to-moderate asthma at the same daily dose.", "With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLU-HFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses.\n Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 micro g/day followed by 1000 micro g/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV(1)) of 20% or more (methacholine PD(20)) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC).\n For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD(20) compared with baseline. The improvement was not significantly greater with 1000 micro g/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p<0.05) lower values at 1000 micro g/day for BEC-HFA versus FLU-HFA (1.97 fold difference (95% CI 1.28 to 3.02)).\n There was no difference in the airway and systemic effects in patients with mild to moderate asthma between FLU-HFA and BEC-HFA at a dose of 500 micro g/day. At 1000 micro g/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy.", "Inhaled corticosteroids provide first-line treatment for asthma. An advance to improve potency was to produce new molecules with increased glucocorticoid receptor affinity (eg, fluticasone propionate [FP]). An alternative is to deliver more medication to both the large and small airway inflammation of asthma by using an extrafine aerosol (eg, beclomethasone dipropionate extrafine aerosol [BDP-extrafinel).\n To demonstrate clinical equivalence of BDP-extrafine (400 microg daily) and FP (400 microg daily) in symptomatic asthmatic patients over the course of 6 weeks.\n This was a double-blind, double-dummy, parallel-group, multicenter, 6-week study in adults with asthma taking conventional FP 100 to 250 microg daily or equivalent, and displaying signs/symptoms of active disease requiring additional therapy.\n Eighty-eight patients were randomized to BDP-extrafine (and FP-placebo) and 84 to FP (and BDP-placebo). There were no significant differences between treatments with respect to symptom control, as evidenced by mean change from baseline in percentage days without asthma symptoms/nights without sleep disturbance observed at weeks 1 to 2, 3 to 4, or 5 to 6. Mean changes from baseline in AM PEFR at weeks 5 to 6 for BDP-extrafine (19.0) and FP (30.5) were equivalent (P = 0.022 for equivalence). There were significant (P < 0.001) within-treatment-group differences in mean change from baseline in AM PEFR at weeks 1 to 2 for both treatments. There was no difference in the incidence of patients reporting at least one adverse event during the study (BDP-extrafine 41%; FP 37%). Mean percentage change from baseline for AM plasma cortisol at week 6 was + 17.7% for BDP-extrafine and +4.2% for FP (P = 0.066 for difference).\n BDP-extrafine and FP at doses of 400 microg daily provided equivalent asthma control in patients with symptomatic asthma and exhibited similar safety profiles.", "Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extra-fine aerosol and HFA-fluticasone propionate (HFA-FP) are chlorofluorocarbon-free inhalers. We conducted an 8-week, open study to demonstrate the equivalence of HFA-BDP (800 microg day(-1)) and HFA-FP (1000 microg day(-1)) in moderate to severe asthma. Symptomatic patients on 500-1000 microg day(-1) CFC-BDP (or equivalent) and short-acting beta-agonist, were randomized to HFA-BDP (n = 101) or HFA-FP (n = 97) after 7-14 (+/-2) day run-in. In the intent-to-treat (ITT) population (n = 198), both treatments provided clinically and statistically significant improvements in asthma control, with increases in peak expiratory flow in the morning (AM PEF) and asthma symptoms (within treatment analysis P<0.05). Mean (SE) change in AM PEF from baseline at week 8 was equivalent (defined as 90% CI for the mean difference between treatments within +/-25 l min(-1)) in the two groups: 29.59 (5.19) l min(-1) for HFA-BDP vs. 17.3 (5.45) l min(-1) for HFA-FP (90% CI-0.02, 24.91). For the perprotocol population (n = 121), the mean (SE) change in AM PEF from baseline was not equivalent; AM PEF improved to a significantly greater extent in the HFA-BDP group than HFA-FP group [34.84 (7.08) vs. 20.63 (7.32) l min(-1) P<0.01; 90% CI; 2.66, 31.10]. At week 8 in the ITT population, there were no statistically significant differences in FEV1, beta-agonist use, asthma symptom/sleep disturbance scores, or percentage of days without asthma symptoms/sleep disturbance. There was a significantly greater reduction from baseline in mean eosinophil count for HFA-BDP compared with HFA-FP at weeks 3 and 8 (P<0.01), and eosinophil cationic protein value at week 8 (P<0.01). Both treatments were well tolerated and there were no statistically significant differences in urinary cortisol creatinine parameters. In conclusion, this study showed that, in patients with moderate-to-severe symptomatic asthma, HFA-BDP extra-fine aerosol 800 microg(-1) was at least as effective and equally well tolerated as 1000 microg day(-1) HFA-FP.", "Extra-fine hydrofluoroalkane-beclomethasone differs from other inhaled corticosteroids by its fine aerosol characteristics. Therefore, extra-fine hydrofluoroalkane-beclomethasone may be particularly useful for treating peripheral airway inflammation in asthma.\n To analyze the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler (DPI) in asthmatic children by measuring bronchial and alveolar nitric oxide (NO) and inflammatory markers in exhaled breath condensate (EBC).\n In a 6-month crossover study, 33 children aged 6 to 12 years with moderate persistent asthma were randomly treated with extra-fine hydrofluoroalkane-beclomethasone (200 microg daily via an Autohaler) and fluticasone DPI (200 microg daily via a Diskus). The primary outcome variables were alveolar NO concentration and bronchial NO flux. The secondary outcome variables were levels of inflammatory markers in EBC, lung function indices, symptoms, exacerbations, and adverse effects. All the variables were recorded at baseline and after each treatment period.\n Mean +/- SE alveolar NO concentration and bronchial NO flux were comparable after treatment with hydrofluoroalkane-beclomethasone vs fluticasone DPI (4.7 +/- 0.5 vs 4.3 +/- 0.5 ppb, P = .55, and 1,124.3 +/- 253.6 vs 1,029.1 +/- 195.5 pL/s, P = .70, respectively). In addition, levels of inflammatory markers in EBC, lung function indices, and symptoms did not differ between treatments. Patients used fewer beta2-agonists during the last 2 weeks of hydrofluoroalkane-beclomethasone treatment.\n The anti-inflammatory effects of hydrofluoroalkane-beclomethasone are similar to those of fluticasone DPI in children with moderate persistent asthma." ]

[ "19262394", "9651462", "10433531", "16651912" ]

[ "Pronation versus supination maneuvers for the reduction of 'pulled elbow': a randomized clinical trial.", "A comparison of supination/flexion to hyperpronation in the reduction of radial head subluxations.", "Radial head subluxation: comparing two methods of reduction.", "Randomized comparison of pain perception during radial head subluxation reduction using supination-flexion or forced pronation." ]

[ "The purpose of this study was to compare the efficiency of the hyperpronation and supination-flexion maneuvers in the reduction of the pulled elbow.\n Sixty-six patients with pulled elbow were randomized for reduction with either hyperpronation or supination-flexion maneuvers. When the first attempt failed, a second attempt was performed with the same reduction maneuver. After failure of the second attempt the reduction maneuver was changed to the alternate method. The success rate of the reductions and the subjective rating on the difficulty of the reduction by the physician were recorded and analyzed statistically.\n Thirty-two of 34 patients (94%) in the hyperpronation group and 22 of 32 patients (69%) in the supination-flexion group were reduced at first attempt (P=0.007). Two patients in the hyperpronation group and seven patients in the supination-flexion group were reduced at the second attempt. Reduction rates were statistically similar (P=0.06). Three patients in the supination-flexion group had failed reduction at the second attempt and the reduction maneuver needed to be changed. They were successfully reduced with hyperpronation maneuver at the first attempt. Final success rate of the hyperpronation maneuver at the first attempt was statistically higher than the supination-flexion maneuver (P=0.004). Furthermore, the hyperpronation maneuver was rated significantly easier than the supination-flexion maneuver by physicians (P=0.003).\n Although final reduction rates were similar, the hyperpronation maneuver was more efficient at the first attempt, easier for physicians and less painful for the children.", "To compare supination at the wrist followed by flexion at the elbow (the traditional reduction technique) to hyperpronation at the wrist in the reduction of radial head subluxations (nursemaid's elbow).\n This prospective, randomized study involved a consecutive sampling of children younger than 6 years of age who presented to one of two urban pediatric emergency departments and two suburban pediatric ambulatory care centers with a clinical diagnosis of radial head subluxation. Patients were randomized to undergo reduction by one of the two methods and were followed every 5 minutes for return of elbow function. The initial procedure was repeated if baseline functioning did not return 15 minutes after the initial reduction attempt. Failure of that technique 30 minutes after the initial reduction attempt resulted in a cross-over to the alternate method of reduction. The alternate procedure was repeated if baseline functioning did not return 15 minutes after the alternate procedure was attempted. If the patient failed both techniques, radiography of the elbow was performed.\n A total of 90 patients were enrolled in the study. Five patients were removed from further analysis secondary to a final diagnosis of fracture, 84 were reduced successfully, and 1 failed both techniques. Demographic characteristics of each group were similar. Thirty-nine of 41 patients (95%) randomized to hyper-pronation were reduced successfully on the first attempt versus 34 of 44 patients (77%) randomized to supination. Two patients in the hyperpronation group required two attempts versus 10 patients in the supination group. Hyperpronation was more successful; 40 of 41 patients (97.5%) in the hyperpronation group were reduced successfully versus 38 of 44 patients (86%) in the supination group. Of the 6 patients who crossed over from supination to hyperpronation, 5 were reduced on the first attempt and 1 was reduced on the second attempt.\n In the reduction of radial head subluxations, the hyperpronation technique required fewer attempts at reduction compared with supination, was successful more often than supination, and was often successful when supination failed.", "To determine whether reduction of radial head subluxation (RHS) is more successful using pronation and flexion (PF) vs the more widely used supination and flexion (SF) method.\n Prospective study in a tertiary care children's hospital ED from August 1996 through December 1997. Inclusion criteria included age <7 years with an upper-extremity injury. Exclusion criteria included neurologic impairment, congenital malformation, or obvious bony deformity or edema. Patients were randomized to receive either PF or SF. Reduction was considered successful if the child used the injured arm. Both the physician and the parent rated the child's pain during the procedure using a descriptive ordinal scale, from 0 (no pain) to 3 (severe pain).\n 148 patients were enrolled; 13 were excluded. Success was achieved on the first attempt in 53/67 (80%, 95% CI = 0.67 to 0.88) of patients receiving PF and in 47/68 (69%, 95% CI = 0.57 to 0.80) of those receiving SF (p = 0.186). For those injuring the left arm, 29/41 (71%, 95% CI = 0.54 to 0.84) were successfully reduced using SF, while 33/37 (89%, 95% CI = 0.75 to 0.97) were successfully reduced using PF (p = 0.044). Physicians perceived PF to be less painful than SF (p = 0.013). There was no significant pain score difference rated by parents.\n Both PF and SF can be used with success to reduce RHS. For left arm injuries, PF should be attempted first, since it may decrease the need for further treatment. PF may be less painful, particularly for first reduction attempts.", "To determine if a difference exists in perceived pain between the forced pronation and supination-flexion methods of radial head subluxation (RHS) reduction.\n We developed a prospective randomized trial of children aged 6 months to 7 years who presented to the emergency department (ED) at Miami Children's Hospital with an immobile arm and physical findings suggestive of RHS. Children were randomized into 2 groups for RHS reduction: forced pronation and supination-flexion. Parents, physicians, and nurses were given a standard visual analog pain scale for pain assessment before, during, and at 1 minute after successful reduction.\n Seventy-five children presented to the ED with RHS; 3 children were excluded from the study because of nonadherence to the protocol and another 9 were excluded because of unsuccessful reduction during the first attempt. Of the remaining children, 32 children underwent forced pronation and 31 underwent supination-flexion. Physicians did not find a significant difference in gain scores between their perceptions of the premeasure and postmeasure of pain between those patients receiving supination-flexion and those receiving forced pronation. For nurses (P < 0.031) and parents (P < 0.043), there were statistically significant differences in gain scores. Nurses and parents perceived forced pronation as being less painful. The mean difference for parents was 1.7 cm, which exceeded the value of 1.3 cm identified as clinically significant.\n Forced pronation is perceived as less painful than the supination-flexion method by parents of children treated for RHS in our ED." ]

[ "7684865", "12885803", "17544845", "12873686", "15134985", "11437096", "9389919", "17325585", "1717669", "12215552", "9552068", "2460352", "10025832", "1716935" ]

[ "Strontium-89 as an adjuvant to external beam radiation improves pain relief and delays disease progression in advanced prostate cancer: results of a randomized controlled trial.", "Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: tandomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate.", "Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study.", "Role of strontium-89 as adjuvant to palliative external beam radiotherapy is questionable: results of a double-blind randomized study.", "Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer.", "Metastatic bone pain palliation with 89-Sr and 186-Re-HEDP in breast cancer patients.", "A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases.", "89Sr versus 153Sm-EDTMP: comparison of treatment efficacy of painful bone metastases in prostate and breast carcinoma.", "Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo.", "The PLACORHEN study: a double-blind, placebo-controlled, randomized radionuclide study with (186)Re-etidronate in hormone-resistant prostate cancer patients with painful bone metastases. Placebo Controlled Rhenium Study.", "Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.", "Results of a double blind study of 89-strontium therapy of skeletal metastases of prostatic carcinoma.", "Relative efficacy of 32P and 89Sr in palliation in skeletal metastases.", "A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone." ]

[ "In a multicenter, randomized controlled trial involving 126 patients with endocrine-resistant advanced prostate cancer, all of whom received external beam radiotherapy, additional treatment with a single injected dose of 400 MBq strontium-89 (Metastron) significantly improved overall pain control. Adjuvant therapy with strontium-89 also significantly reduced analgesia requirements compared with placebo and delayed disease progression, as indicated by the requirement for further external beam radiotherapy. On certain measures, patients receiving strontium-89 also showed enhanced quality of life. Accompanying these changes, levels of prostate tumor markers were significantly reduced by strontium-89 treatment. The benefits resulting from adjuvant strontium therapy were associated with tolerable hematologic toxicity. The addition of strontium-89 to external beam radiation had no effect on survival. However, it has clear implications for improved palliation in advanced prostate cancer and may also impact positively on treatment costs.", "We investigated the effect of repeated bone-targeted therapy with rhenium-188 hydroxyethylidenediphosphonate (HEDP) in patients with progressive, hormone-resistant prostate carcinoma and bone pain. The aim of this study was to determine the pain palliation and the antitumor effect of rhenium-188 HEDP treatments.\n Sixty-four patients were randomly assigned to one of two groups for radionuclide therapy with rhenium-188 HEDP; patients of group A received a single injection, patients of group B received two injections (interval, 8 weeks). After therapy, patients were followed-up by assessment of pain palliation and clinical outcome until death.\n In both groups, toxicity was low, with moderate thrombopenia and leukopenia (maximum common toxicity criteria grade of 2). The effectiveness of rhenium-188 HEDP for pain palliation was better in the repeated treatment group (group B), with a response rate and time of response of 92% and 5.66 months, respectively (P =.006 and P =.001). In group B, 11 (39%) of 28 patients had a prostate-specific antigen decrease of more than 50% for at least 8 weeks, compared with two (7%) of 30 patients in the single-injection group (group A). The median times to progression of group A and group B were 2.3 months (range, 0 to 12.2 months) and 7.0 months (range, 0 to 24.1 months), respectively (P =.0013), and the median overall survival times were 7.0 months (range, 1.3 to 36.7 months) and 12.7 months (range, 4.1 to 32.2 months), respectively (P =.043).\n Compared with single-injection therapy, repeated bone-targeted therapy with rhenium-188 HEDP administered to patients with advanced progressive hormone-refractory prostate carcinoma enhanced pain palliation and improved progression-free and overall survival. Larger studies are justified to further evaluate the use of rhenium-188 HEDP.", "The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of (223)Ra.\n Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat.\n Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued (223)Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression).\n (223)Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers.", "To explore the efficacy of adjuvant (89)Sr applied with external beam radiotherapy (EBRT) to treat bone metastases.\n Ninety-five patients were randomized to (89)Sr (Arm A) or saline (Arm B) on Day 1 of EBRT to demonstrate a reduction in 3-month physician-assessed subjective progression from 70% to 45%.\n At 3 and 6 months, no difference between treatment arms was observed in the progression rate. At 3 months, the physician-assessed response rate for all patients was 25%, with 46% of the patients progressing. The pretreatment use of opiates was independently associated with short progression-free survival. On the basis of the quality-of-life assessments, pain relief occurred in 50% of patients and 32% experienced improvement in global quality of life, without impact from (89)Sr. Differences were observed between the physician evaluation of radiotherapy efficacy and the patient assessment. In Arm A, serum alkaline phosphatase, but not serum prostate-specific antigen, decreased during the first 3 months after treatment.\n (89)Sr, adjuvant to ERBT, does not seem to reduce the number of patients with subjective progression at 3 months. Patients should be referred for palliative RT before their bone pain requires high doses of opiates. In radiotherapy trials, the evaluation of pain and pain relief remains problematic because of the confounding use of analgesics.", "A Phase III randomized trial was designed to assess the effectiveness of samarium-153 (153Sm)-lexidronam for palliation of bone pain in patients with hormone-refractory prostate cancer.\n A total of 152 men with hormone-refractory prostate cancer and painful bone metastases were enrolled in a prospective, randomized, double-blind trial comparing radioactive (153Sm) versus nonradioactive (152Sm) lexidronam complexes. Patients were randomized (2:1) to the radioactive (153Sm) agent. Patient diaries recording daily pain and analgesic use were completed during a planned 16-week evaluation period. Nonresponders were informed of the treatment received after 4 weeks of treatment and, if initially treated with placebo, were allowed to receive 153Sm-lexidronam in an open-label fashion. Pain was measured using validated patient-derived visual analog scales and pain descriptor scales.\n 153Sm-lexidronam had positive effects on measures of pain relief compared with placebo within 1 to 2 weeks. Reductions in opioid use were recorded at weeks 3 and 4. Because nonresponders were unblinded at week 4, statistical comparisons between the arms beyond week 4 were not possible. Mild, transient bone marrow suppression was the only adverse event associated with 153Sm-lexidronam administration. The mean nadir white blood cell and platelet count (3 to 4 weeks after treatment) was 3800/microL and 127,000/microL, respectively. Counts recovered to baseline after approximately 8 weeks. No grade 4 decreases in either platelets or white bloods cells were documented.\n These findings demonstrate that 1 mCi/kg 153Sm-lexidronam is both safe and effective for the palliation of painful bone metastases in patients with hormone-refractory prostate cancer.", "The study evaluates the therapeutic efficacy of Strontium-89-chloride (89Sr) and 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) in the palliation of painful bone metastases from breast cancer.\n Fifty patients with painful multifocal bone metastases from breast cancer entered the study and were randomized into two groups according to the radiopharmaceutical used: 148 MBq 89Sr i.v. (Group A: 25 patients) and 1406 MBq 186Re-HEDP i.v. (Group B: 25 patients). Pain palliation was evaluated on the basis of the Wisconsin pain test improvement at two months and response was graded as complete, partial, minimal or absent. Hematological toxicity and side effects were reported according to WHO guidelines.\n The global response rate was 84% (21/25) for 89Sr and 92% (23/25) for 186Re-HEDP, respectively. The onset of pain palliation appeared significantly earlier in Group B (p < 0.0001). The duration of pain relief ranged from two months to 14 months (mean of 125 days with a median value of 120 days) in Group A and from one month to 12 months (mean of 107 days with a median value of 60 days) in Group B (p = 0.39). A moderate hematological toxicity was apparent in both groups. Platelet and white blood cell counts returned to baseline levels within 12 weeks after 89Sr administration and 6 weeks after 186Re-HEDP administration (p < 0.01).\n Both 89Sr and 186Re-HEDP are effective and safe in bone pain palliation in breast cancer with the latter showing a significantly faster onset of pain relief.", "One hundred and fourteen patients with painful bone metastases participated in this randomised, dose-controlled study of the efficacy and safety of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP), a systemically administered radiopharmaceutical. Fifty-five patients received single doses of 0.5 mCi/kg and 59 patients received single doses of 1.0 mCi/kg. Treatment with 153-Sm-EDTMP produced improvement from baseline in all patient-rated efficacy assessments, including degree of pain, level of daytime discomfort, quality of sleep and pain relief. During the first 4 weeks after dose administration, when the patients evaluated efficacy daily, there were statistically significant changes from baseline with the 1.0 mCi/kg dose but not with the 0.5 mCi/kg dose. The difference between doses in visual analogue pain scores was statistically significant at week 4 (P = 0.0476). Among subsets of patients examined, female patients with breast cancer receiving 1.0 mCi/kg had the most noticeable improvement. The physicians judged that approximately half of the patients in each dose group were experiencing some degree of pain relief by week 2. This value increased to 55% for the 0.5 mCi/kg group and 70% for the 1.0 mCi/kg group at week 4. More patients in the higher dose group (54%) than in the lower dose group (44%) completed the 16-week study. A predictable level of dose-related marrow suppression was the only toxicity associated with 153Sm-EDTMP treatment. Values for platelets and WBCs reached nadirs at 3 or 4 weeks with both doses and recovered by 8 weeks. Even at their lowest point, the values were generally higher than those associated with infectious or haemorrhagic complications. Myelotoxicity was no greater in female patients than in male patients. Long-term follow-up revealed longer survival among breast cancer patients who had received the higher dose than among those who had received the lower dose. The results suggest that the 1.0 mCi/kg dose of 153Sm-EDTMP is safe and effective for the treatment of painful bone metastases.", "Painful bone metastases are most frequent in patients with advanced prostate or breast carcinoma. The aim of this study was to compare the analgesic effect of radionuclide therapy using Sr and Sm-EDTMP in patients with painful bone metastases of these tumours.\n One hundred patients treated with radionuclide bone palliation therapy were analysed. The study population consisted of 60 male patients with advanced prostate carcinoma and 40 female patients with advanced breast carcinoma. Fifty patients (30 men and 20 women) were treated with Sr (150 MBq). The other 50 patients were treated with Sm-EDTMP (37 MBq x kg). The treatment efficacy was evaluated by a visual analogue scale (VAS), Karnofsky performance scale, and dosage of analgesic drugs used.\n Complete pain relief was found in 40% of women and 40% of men treated using Sm-EDTMP and in 25% of women and 33% of men treated with Sr. No analgesic effect occurred in 20% of patients. A better analgesic effect was found in cases of osteoblastic metastases compared to mixed metastases. Statistically significant reduction of pain intensity, use of analgesic drugs and improvement of performance in Karnofsky scale was found in cases of both radionuclides.\n The analgesic effects of Sr and Sm-EDTMP was similar in both prostate and breast carcinoma. However, the effect was dependent on the type of metastases; better response was observed in cases of osteoblastic metastases than in patients with mixed metastases. Severe adverse reactions after this therapy were rare.", "Rhenium-186 (tin) hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that simultaneously localizes in multiple skeletal metastases in patients with advanced cancer. A single intravenous administration of 30-35 mCi (1110-1295 MBq) is associated with a prompt, significant relief of osseous pain in about 80% of such patients. The efficacy of this new compound was evaluated further by utilizing a double-blind crossover comparison with 99mTc-methylene diphosphonate (MDP) as a radioactive placebo. The new rhenium compound resulted in a significantly (p less than 0.05) greater decrease in pain than did treatment with the radioactive placebo. Rhenium-186(Sn)HEDP appears to be a useful new compound for the palliation of painful skeletal metastases.", "(186)Re-1,1-hydroxyethylidene diphosphonate (etidronate) can be used for the palliative treatment of metastatic bone pain. A randomized, placebo-controlled study using (186)Re-etidronate was conducted on end-stage prostate cancer patients with metastatic bone pain.\n Pain relief was assessed using an electronic diary containing questions reflecting the multidimensional character of chronic pain. The diary was marked twice daily for a maximum of 14 wk (2 wk before and 12 wk after the injection). Pain response was determined using a specific decision rule in which pain intensity, medication index, and daily activities were the core determinants. A positive response day was defined as a day on which pain intensity was reduced > or = 25% compared with baseline values, while medication index and daily activities were at least constant, or on which pain intensity was reduced < 25% and medication index or daily activities improved > or = 25%, without worsening of the remaining factor. The total response (%) was defined as the number of positive response days divided by the number of days of follow-up.\n Of the 111 included patients, 79 were evaluable (43 (186)Re-etidronate, 36 placebo). Thirty-two patients were excluded from the analysis because of incomplete datasets. The total response of the patients treated with (186)Re-etidronate varied from 0% to 96% (mean, 27%, or 23/84 d). In the placebo group, the total response varied from 0% to 80% (mean, 13%, or 11/84 d; Mann-Whitney U test, P < 0.05). The number of patients who requested radiotherapy was higher in the placebo group (67%) than in the (186)Re-etidronate group (44%) (relative risk, 1.51; Fisher's exact test, P = 0.069).\n This randomized controlled trial confirmed that, compared with placebo, (186)Re-etidronate resulted in a significantly longer pain response in the treatment of bone pain from metastasized prostate cancer.", "To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study.\n Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia.\n One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity.\n A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.", "Forty-nine patients were treated with either 3 x 75 MBq 89Sr or saline as placebo. Analysis of results 1 to 3 years after therapy revealed the ineffectiveness of 89Sr to relieve pain from metastases. Unexpectedly, a higher survival rate was found after Sr application (46% vs 4% after 2 years). Covariate analysis underlines the effect of 89Sr therapy on life expectation.", "32p and 89Sr have been shown to produce significant pain relief in patients with skeletal metastases from advanced cancer. Clinically significant pancytopenia has not been reported in doses up to 12 mCi (444 MBq) of either radionuclide. To date, no reports comparing the relative efficacy and toxicity of the two radionuclides in comparable patient populations have been available. Although a cure has not been reported, both treatments have achieved substantial pain relief. However, several studies have used semiquantitative measures such as \"slight,\" \"fair,\" \"partial\" and \"dramatic\" responses, which lend themselves to subjective bias. This report examines the responses to treatment with 32P or 89Sr by attempting a quantification of pain relief and quality of life using the patients as their own controls and compares toxicity in terms of hematological parameters.\n Thirty-one patients with skeletal metastases were treated for pain relief with either 32P (16 patients) or 89Sr (15 patients). Inclusion criteria were pain from bone scan-positive sites above a subjective score of 5 of 10 despite analgesic therapy with narcotic or non-narcotic medication, limitation of movement related to the performance of routine daily activity and a predicted life expectancy of at least 4 mo. The patients had not had chemotherapy or radiotherapy during the previous 6 wk and had normal serum creatinine, white cell and platelet counts. 32P was given orally as a 12 mCi dose, and 89Sr was given intravenously as a 4 mCi (148 MBq) dose. The patients were monitored for 4 mo.\n Complete absence of pain was seen in 7 of 16 patients who were given 32P and in 7 of 15 patients who were given 89Sr. Pain scores fell by at least 50% of the pretreatment score in 14 of 16 patients who were given 32P and 14 of 15 patients who were given 89Sr. Mean duration of pain relief was 9.6 wk with 32P and 10 wk with 89Sr. Analgesic scores fell along with the drop in pain scores. A fall in total white cell, absolute granulocyte and platelet counts occurred in all patients. Subnormal values of white cells and platelets were seen in 5 and 7 patients, respectively, with 32P, and in 0 and 4 patients, respectively, after 89Sr therapy. The decrease in platelet count (but not absolute granulocyte count) was statistically significant when 32P patients were compared with 89Sr patients. However, in no instance did the fall in blood counts require treatment. Absolute granulocyte counts did not fall below 1000 in any patient. There was no significant difference between the two treatments in terms of either efficacy or toxicity.\n No justification has been found in this study for the recommendation of 89Sr over the considerably less expensive oral 32P for the palliation of skeletal pain from metastases of advanced cancer.", "The palliative efficacy of strontium-89 chloride has been evaluated in a prospective double-blind crossover study comparing it with stable strontium as placebo in 32 patients with prostate cancer metastatic to bone. Response was assessed 5 weeks after each treatment. 26 patients were evaluable. Complete pain relief was only reported following strontium-89 injection. Statistical comparison between placebo and strontium-89 showed clear evidence of a therapeutic response to strontium-89 compared with only a limited placebo effect (P less than 0.01)." ]

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[ "Reduction in new metastases in breast cancer with adjuvant clodronate treatment.", "Clodronate decreases the frequency of skeletal metastases in women with breast cancer.", "Efficacy of pamidronate in breast cancer with bone metastases: a randomized, double-blind placebo-controlled multicenter study.", "Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer.", "Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial.", "Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy.", "Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion.", "Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases.", "Long-term controlled trial with diphosphonate in patients with osteolytic bone metastases.", "Endocrine therapy plus zoledronic acid in premenopausal breast cancer.", "Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomised, placebo-controlled phase III studies.", "Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant chemotherapy for early-stage breast cancer.", "Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. The Aredia Multinational Cooperative Group.", "Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates.", "Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study.", "Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer.", "Ibandronate is effective in preventing skeletal events in patients with bone metastases from colorectal cancer.", "Bisphosphonate treatment in primary breast cancer: results from a randomised comparison of oral pamidronate versus no pamidronate in patients with primary breast cancer.", "Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST Study.", "Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial.", "Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials.", "Adjuvant clodronate treatment does not reduce the frequency of skeletal metastases in node-positive breast cancer patients: 5-year results of a randomized controlled trial.", "Controlled clinical study on the use of dichloromethylene diphosphonate in patients with breast carcinoma metastasizing to the skeleton.", "Adjuvant clodronate therapy in patients with locally advanced breast cancer--long term results of a double blind randomized trial. Slovak Clodronate Collaborative Group.", "Zoledronic acid effectively prevents aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST study 36-month follow-up results.", "Oral clodronate in breast cancer patients with bone metastases: a randomized study.", "[Double-blinded controlled study comparing clodronate versus placebo in patients with breast cancer bone metastases].", "Does supportive pamidronate treatment prevent or delay the first manifestation of bone metastases in breast cancer patients?" ]

[ "Bisphosphonates are effective against the increased bone resorption caused by certain diseases because they inhibit the activity of osteoclasts. In patients who have breast cancer and metastatic bone disease, the bisphosphonate clodronate (clodronic acid) reduces the frequency of skeletal complications. Experiments in animals and preliminary clinical observations indicate that early clodronate therapy reduces the incidence of new bony metastases in breast cancer. We investigated the effects of clodronate on the incidence and extent of new metastases in patients with breast cancer.\n Between 1990 and 1995, 302 patients with primary breast cancer and tumor cells in the bone marrow (the presence of which is a risk factor for the development of distant metastases) were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for two years (157 patients) or standard follow-up (145 patients). The median length of observation was 36 months. All patients in both groups received standard surgical treatment and customary hormonal therapy or chemotherapy.\n Distant metastases were detected in 21 patients in the clodronate group and in 42 patients in the control group (P<0.001). The incidence of both osseous and visceral metastases was significantly lower in the clodronate group than in the control group (P=0.003 for both osseous and visceral metastases). Six patients in the clodronate group died, as did 22 in the control group (P=0.001). The mean number of bony metastases per patient in the clodronate group was roughly half that in the control group (3.1 vs. 6.3).\n Clodronate can reduce the incidence and number of new bony and visceral metastases in women with breast cancer who are at high risk for distant metastases.", "The aims of this study were to determine the effects of the bisphosphonate, clodronate, on the incidence of skeletal metastases and associated morbidity in women with advanced breast cancer. 133 women with recurrent breast cancer, but no evidence of skeletal metastases, were randomly allocated to receive clodronate 1600 mg daily by mouth or an identical placebo for 3 years under double-blind conditions at two clinical oncology centers in the UK and Canada. Main outcome measures included the occurrence of skeletal metastases, as judged by sequential bone scans and radiographs, and the morbidity associated with skeletal metastases comprising the incidence of hypercalcemia, vertebral, and nonvertebral fractures, and bone pain assessed by the requirements for skeletal radiotherapy. The number of patients developing skeletal metastases was lower in clodronate-treated patients than with placebo (15 vs. 19), but was not significantly different. The number of skeletal metastases was significantly lower with clodronate treatment than with placebo (32 vs. 63; p < 0.005). The complications of skeletal disease were fewer by 26% in clodronate-treated patients compared to controls (p < 0.01). Compared to placebo, significant effects in favor of clodronate were observed for vertebral deformities (29%) and nonvertebral fractures (75%), but the event frequency of each was low. There was a small (22%) but nonsignificant treatment effect on the requirements for radiotherapy and hypercalcemia (39%). There was no effect of clodronate on survival. We conclude that clodronate by mouth significantly decreases the number and complications of skeletal metastases in women with advanced breast cancer.", "To evaluate the efficacy of pamidronate 60 mg i.v. q 4 weeks in women with advanced breast cancer with skeletal metastases.\n 404 woman with skeletal metastases from breast cancer in Sweden and Norway were included in a randomized, placebo-controlled, multicenter study. Except for the study medication, other palliative treatment was chosen at the discretion of the physician. Skeletal related events, i.e. increased pain, treatment of hypercalcemia, pathologic fractures of long bones or pelvis, paralyses due to vertebral compression, palliative radiotherapy for skeletal metastases, surgery on bone and change of antitumor therapy were recorded every third month as well as a self-estimated pain-score using visual Analog Scales and analgesic consumption.\n There was a significantly increased time to progression of pain (p < 0.01), to hypercalcemic events (p < 0.05) as well as for the cumulative number of skeletal related events (p < 0.01) in favor for the pamidronate group. No statistically significant reduction of pathologic fractures of long bones or pelvis, or pareses due to vertebral compression occurred. No statistically significant differences were found for the need of radiotherapy and surgery on bone. The pamidronate group faired better regarding performance status (p < 0.05). There was a statistically not significant lower consumption of opioid analgesics in the pamidronate group (p = 0.14).\n Pamidronate 60 mg i.v. q 4 weeks reduces skeletal events and improves the quality of life in women with bone metastases from breast cancer.", "Osteolytic metastases often give rise to hypercalcemia, fracture, and bone pain, and occur commonly in patients with recurrent breast cancer. We assessed the bisphosphonate, clodronate, which has proven to be a useful treatment for hypercalcemia and may be a potent inhibitor of tumor-induced osteolysis, for its effect on reducing the osseous complications of metastatic breast cancer.\n We studied 173 patients with bone metastases due to breast cancer in a randomized, double-blind, placebo-controlled trial of oral clodronate 1,600 mg/d (85 patients) compared with an identical placebo (88 patients).\n The patients in each wing were comparable in their clinical, radiologic, and biochemical characteristics at trial entry. In patients who received clodronate, there was a significant reduction compared with placebo in the total number of hypercalcemic episodes (28 v 52; P < .01), in the number of terminal hypercalcemic episodes (seven v 17; P < .05), in the incidence of vertebral fractures (84 v 124 per 100 patient-years; P < .025), and in the rate of vertebral deformity (168 v 252 per 100 patient-years; P < .001). The combined rate of all morbid skeletal events was significantly reduced (218.6 v 304.8 per 100 patient-years; P < .001). Trends were seen in favor of clodronate for nonvertebral fracture rates and radiotherapy requirements for bone pain (particularly spinal pain). No significant survival differences and no significant differences in side effects were observed between the two groups.\n These findings indicate that oral clodronate has a beneficial effect on the skeletal morbidity associated with breast cancer and should be considered as antiosteolytic therapy in affected patients. It deserves further investigation as an adjuvant therapy in operable breast cancer and in patients with nonosseous recurrence who are at high risk for bone metastases.", "To investigate the efficacy and safety of zoledronic acid for the treatment of bone metastases from breast cancer.\n Women with bone metastases (N = 228) were randomly assigned to receive 4 mg zoledronic acid (n = 114) or placebo (n = 114) via 15-minute infusions every 4 weeks for 1 year. The primary efficacy end point was the skeletal-related event (SRE) rate ratio between treatment groups. An SRE was defined as pathologic fracture, spinal cord compression, and radiation or surgery to bone. Secondary end points included percentage of patients with at least one SRE, time-to-first SRE, and Andersen-Gill multiple-event analysis.\n The SRE rate ratio at 1 year (excluding HCM and adjusted for prior fracture) was 0.61 (permutation test; P = .027), indicating that zoledronic acid reduced the rate of SRE by 39% compared with placebo. The percentage of patients with at least one SRE (excluding HCM) was significantly reduced by 20% by zoledronic acid (29.8% v 49.6% for placebo; P = .003). Zoledronic acid significantly delayed time-to-first SRE (median not reached v 364 days; Cox regression; P = .007) and reduced the risk of SREs by 41% in multiple event analysis (risk ratio = 0.59; P = .019) compared with placebo. Zoledronic acid was well tolerated with a safety profile similar to placebo. No patient treated with zoledronic acid had grade 3 or 4 serum creatinine increase.\n Zoledronic acid significantly reduced skeletal complications compared with placebo across multiple end points in Japanese women with bone metastases from breast cancer.", "Denosumab, a fully human monoclonal antibody to RANKL, suppresses bone resorption. This study evaluated the effects of denosumab in i.v. bisphosphonate (IV BP)-naïve patients with breast cancer-related bone metastases.\n Eligible women (n = 255), stratified by type of antineoplastic therapy, were randomized to 1 of 5 blinded denosumab cohorts or an open-label IV BP cohort. Denosumab was administered s.c. every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg) through 21 weeks. Final efficacy results for up to 25 weeks are reported, including percentage change from baseline in urine N-telopeptide corrected for creatinine (uNTx/Cr) and incidence of skeletal-related events (SRE). Safety results are reported through the end of follow-up (up to 57 weeks).\n At week 13 and 25, the median percent changes in uNTx/creatinine (Cr) among patients with measurable uNTx were -73% and -75% for the pooled denosumab groups and -79% and -71% for the IV BP group. Among patients with > or =1 postbaseline measurement of uNTx at week 25, 52% (109 of 208) of denosumab-treated patients and 46% (19 of 41) of IV BP-treated patients achieved >65% uNTx/Cr reduction. On-study SREs occurred in 12% (26 of 211) of denosumab-treated patients and 16% (7 of 43) of IV BP-treated patients. Overall rates of adverse events were 95% in denosumab and IV BP groups. No denosumab-related serious or fatal adverse events occurred.\n In IV BP-naïve breast cancer patients with bone metastases, denosumab suppresses bone turnover and seems to reduce SRE risk similarly to IV BPs, with a safety profile consistent with an advanced cancer population receiving systemic therapy.", "Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial.\n Overall, 1130 patients with breast carcinoma who had all types of bone metastases (osteolytic, mixed, or osteoblastic by radiology) were randomized to receive treatment with either 4 mg of Zol or 8 mg of Zol as a 15-minute infusion or 90 mg of Pam as a 2-hour infusion every 3-4 weeks for 12 months. A skeletal-related event (SRE) was defined as a pathologic fracture, spinal cord compression, radiotherapy, or surgery to bone.\n Among all patients with BC, the proportion of those who had an SRE (primary endpoint) was comparable between treatment groups (43% of patients who received 4 mg of Zol vs. 45% of patients who received Pam). Among patients who had breast carcinoma with at least 1 osteolytic lesion (n = 528 patients), the proportion with an SRE was lower in the 4-mg Zol group compared with the Pam group (48% vs. 58%), but this did not reach statistical significance (P = 0.058). The time to first SRE was significantly longer in the 4-mg Zol group compared with the Pam group (median, 310 vs. 174 days; P = 0.013). Moreover, multiple-event analysis demonstrated significant further reductions in the risk of developing SREs over the reduction achieved with Pam (30% in the osteolytic subset [P = 0.010] and 20% for all patients with BC [P = 0.037]).\n The current data indicate that treatment with 4 mg of Zol was more effective than 90 mg of Pam in reducing skeletal complications in a subset of patients with breast carcinoma who had at least 1 osteolytic lesion at study entry.\n Copyright 2003 American Cancer Society.", "This phase III study compared the efficacy of the new potent bisphosphonate, ibandronate, with placebo as intravenous (i.v.) therapy in metastatic bone disease due to breast cancer.\n A total of 466 patients were randomised to receive placebo (n = 158), or 2 mg (n = 154) or 6 mg (n = 154) ibandronate every 3-4 weeks for up to 2 years. The primary efficacy parameter was the number of 12-week periods with new bone complications, expressed as the skeletal morbidity period rate (SMPR). Bone pain, analgesic use and safety were evaluated monthly. Results SMPR was lower in both ibandronate groups compared with the placebo group; the difference was statistically significant for the ibandronate 6 mg group (P = 0.004 versus placebo). Consistent with the SMPR, ibandronate 6 mg significantly reduced the number of new bone events (by 38%) and increased time to first new bone event. Patients on ibandronate 6 mg also experienced decreased bone pain scores and analgesic use. Treatment with ibandronate was well tolerated.\n These results indicate that 6 mg i.v. ibandronate is effective and safe in the treatment of bone metastases from breast cancer.", "Thirty-four normocalcaemic women with multiple osteolytic bone metastases from breast cancer were randomly allocated to treatment with disodium dichloromethylene diphosphonate (Cl2MDP) 1600 mg/day orally (17) or placebo (17) for 3-9 months. Fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios declined in the Cl2MDP group but not in the placebo group. Four patients in the placebo group died from hypercalcaemia. New bone metastases were more common in patients on placebo and these patients also required more analgesic drugs than those on Cl2MDP. Cl2MDP seemed to reduce bone pain and bone resorption and prevent the development of hypercalcaemia caused by osteolytic metastases. The formation of new bone metastases and the growth of old ones seemed to be retarded by Cl2MDP.", "Ovarian suppression plus tamoxifen is a standard adjuvant treatment in premenopausal women with endocrine-responsive breast cancer. Aromatase inhibitors are superior to tamoxifen in postmenopausal patients, and preclinical data suggest that zoledronic acid has antitumor properties.\n We examined the effect of adding zoledronic acid to a combination of either goserelin and tamoxifen or goserelin and anastrozole in premenopausal women with endocrine-responsive early breast cancer. We randomly assigned 1803 patients to receive goserelin (3.6 mg given subcutaneously every 28 days) plus tamoxifen (20 mg per day given orally) or anastrozole (1 mg per day given orally) with or without zoledronic acid (4 mg given intravenously every 6 months) for 3 years. The primary end point was disease-free survival; recurrence-free survival and overall survival were secondary end points.\n After a median follow-up of 47.8 months, 137 events had occurred, with disease-free survival rates of 92.8% in the tamoxifen group, 92.0% in the anastrozole group, 90.8% in the group that received endocrine therapy alone, and 94.0% in the group that received endocrine therapy with zoledronic acid. There was no significant difference in disease-free survival between the anastrozole and tamoxifen groups (hazard ratio for disease progression in the anastrozole group, 1.10; 95% confidence interval [CI], 0.78 to 1.53; P=0.59). The addition of zoledronic acid to endocrine therapy, as compared with endocrine therapy without zoledronic acid, resulted in an absolute reduction of 3.2 percentage points and a relative reduction of 36% in the risk of disease progression (hazard ratio, 0.64; 95% CI, 0.46 to 0.91; P=0.01); the addition of zoledronic acid did not significantly reduce the risk of death (hazard ratio, 0.60; 95% CI, 0.32 to 1.11; P=0.11). Adverse events were consistent with known drug-safety profiles.\n The addition of zoledronic acid to adjuvant endocrine therapy improves disease-free survival in premenopausal patients with estrogen-responsive early breast cancer. (ClinicalTrials.gov number, NCT00295646.)\n 2009 Massachusetts Medical Society", "Although intravenous (i.v.) bisphosphonates are the standard of care for metastatic bone disease, they are less than ideal for many patients due to infusion-related adverse events (AEs), an increased risk of renal toxicity and the inconvenience of regular hospital visits. The use of oral bisphosphonate therapy is limited by concerns over efficacy and gastrointestinal (GI) side effects. There remains a clinical need for an oral bisphosphonate that offers equivalent efficacy to i.v. bisphosphonates, good tolerability and dosing convenience. Oral ibandronate, a highly potent, third-generation aminobisphosphonate, has been evaluated in phase III clinical trials of patients with bone metastases from breast cancer. In two pooled phase III studies, patients with breast cancer and bone metastases were randomised to receive oral ibandronate 50 mg (n=287) or placebo (n=277) once daily for up to 96 weeks. The primary end point was the skeletal morbidity period rate (SMPR), defined as the number of 12-week periods with new skeletal complications. Multivariate Poisson's regression analysis was used to assess the relative risk of skeletal-related events in each treatment group during the study period. Oral ibandronate 50 mg significantly reduced the mean SMPR compared with placebo (0.95 vs 1.18, P=0.004). There was a significant reduction in the mean number of events requiring radiotherapy (0.73 vs 0.98, P<0.001) and events requiring surgery (0.47 vs 0.53, P=0.037). Poisson's regression analysis confirmed that oral ibandronate significantly reduced the risk of a skeletal event compared with placebo (hazard ratio 0.62, 95% CI=0.48, 0.79; P=0.0001). The incidence of mild treatment-related upper GI AEs was slightly higher in the oral ibandronate 50 mg group compared with placebo, but very few serious drug-related AEs were reported. Oral ibandronate 50 mg is an effective, well-tolerated and convenient treatment for the prevention of skeletal complications of metastatic bone disease.", "Adjuvant chemotherapy for breast cancer (BC) may be associated with increased rates of bone loss and decreased bone mineral density (BMD) and may lead to premature osteoporosis and increased fracture risk. We examined whether zoledronic acid (ZA) prevents bone loss in premenopausal women receiving chemotherapy for early-stage BC.\n This study is a randomized, double-blind, multicenter, phase III trial comparing ZA (4 mg intravenously every 3 months) versus placebo for 1 year. Premenopausal women underwent serial BMD measurements before initiating chemotherapy and at 6 and 12 months. The primary outcome was percent change in lumbar spine (LS) BMD at 6 months. Secondary outcomes were percent change at any BMD site and markers of bone turnover at 12 months. Linear mixed model analysis for repeated measures was performed.\n Of 101 women who were randomly assigned and completed baseline evaluation, 96 completed the 6-month evaluation, and 85 completed the 12-month evaluation. Baseline characteristics were comparable between the groups. Mean age was 42 years. Placebo was associated with significant decline in LS BMD at both 6 (2.4%) and 12 (4.1%) months. Similarly, total hip BMD declined by 0.8% at 6 months and 2.6% at 12 months. In contrast, BMD remained stable in ZA patients (P < .0001 compared with placebo).\n Premenopausal women receiving chemotherapy for BC sustained significant bone loss at the LS and hip, whereas BMD remained stable in women who received ZA. Administration of ZA during the first year of chemotherapy is an effective and well-tolerated strategy for preventing bone loss.", "Bone metastases are a major cause of morbidity in breast cancer, resulting in complications that include pain, loss of mobility, pathologic fracture, and tumor-induced hypercalcemia (TIH). Inhibition of osteoclast-mediated bone destruction using bisphosphonates represents a promising new management approach.\n Breast cancer patients with bone metastases were randomly allocated to receive chemotherapy alone (152 patients) or chemotherapy plus pamidronate 45 mg in 250 mL of saline as a 1-hour intravenous infusion every 3 weeks (143 patients). Whenever possible, treatment continued until progression of disease (PD) in bone appeared on radiographs or bone scan. Time to PD in bone and pain reduction according to a self-assessment six-point scale were selected as primary end points. PD in bone was verified during extramural review (EMR) of all imaging studies by blinded observers, and these data were used as the main efficacy criterion. Analgesic intake, World Health Organization (WHO) performance status, and complications of bone metastases (radiotherapy, TIH, fractures, orthopedic surgery) were also compared in the two groups.\n At EMR, median time to PD in bone was increased by 48% in patients who received pamidronate (249 v 168 days; P = .02, Wilcoxon test). Marked pain relief, defined as a two-point decrease lasting for > or = 6 weeks, was reported by 44% of pamidronate patients and by 30% of controls (P = .025, chi 2 test). The infusions (median, nine per patient; range, 0 to 39) were well tolerated, with no major toxicities reported. Pamidronate by repeated infusion can significantly slow the progression of bone metastases and reduce attendant morbidity.", "Patients with bone metastases and elevated urinary N-telopeptide (uNTx), representing excessive bone resorption, are at increased risk for skeletal-related events (SREs), cancer progression, and death. Osteoclast-mediated bone resorption is regulated by RANKL. We evaluated the effect of denosumab, a fully human monoclonal antibody against RANKL, in patients with bone metastases and elevated uNTx levels despite ongoing intravenous (IV) bisphosphonate (BP) therapy.\n Eligible patients had histologically confirmed malignancy, > or = 1 bone metastases, and uNTx levels higher than 50 nmol/L bone collagen equivalents (BCE)/mM creatinine despite IV BPs. They were stratified by tumor type and screening uNTx levels (50 to 100 or > 100 nmol/L BCE/mM creatinine), and randomly assigned to continue IV BPs every 4 weeks or receive subcutaneous denosumab 180 mg every 4 weeks or every 12 weeks.\n Among 111 patients accrued, the primary end point of uNTx levels lower than 50 nmol/L BCE/mM creatinine (uNTx < 50) at week 13 was achieved by 49 (71%) of 69 patients in the denosumab arms, compared with 10 (29%) of 35 patients in the IV BP arm (P < .001). The proportion of patients with uNTx lower than 50 was maintained at week 25 (64% denosumab arms; 37% IV BP arm; P = .01). The incidence of SREs was six (8%) of 73 and six (17%) of 35 in the denosumab group and IV BP group, respectively. Rates of adverse events were similar between treatment groups.\n Among patients with elevated uNTx despite ongoing IV BP therapy, denosumab normalized uNTx levels more frequently than the continuation of IV BP. Fewer patients receiving denosumab experienced on-study SREs than those receiving IV BPs.", "This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases.\n Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression).\n Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95% CI, 0.66 to 0.89; P = .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P = .39).\n Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.", "The development of bone metastases depends on tumor-induced osteoclastic resorption of bone, which may be inhibited by the antiosteolytic bisphosphonate clodronate. Given to patients with primary breast cancer, clodronate might reduce the subsequent incidence of bone metastases.\n This double-blind, multicenter trial accrued 1,069 assessable patients with operable breast cancer between 1989 and 1995. All patients received surgery, radiotherapy, chemotherapy, and tamoxifen as required. Patients were randomized to receive oral clodronate 1,600 mg/d or a placebo for 2 years starting within 6 months of primary treatment. The primary end point was relapse in bone, analyzed on an intent-to-treat basis, during the medication period and during the total follow-up period (median follow-up, 2,007 days). Secondary end points were relapse in other sites, mortality, and toxicity.\n During the total follow-up period, there was a nonsignificant reduction in occurrence of bone metastases (clodronate, n = 63; placebo, n = 80; hazards ratio [HR], 0.77; 95% confidence interval [CI], 0.56 to 1.08; P =.127). During the medication period there was a significant reduction in the occurrence of bone metastases (clodronate, n = 12; placebo, n = 28; HR, 0.44; 95% CI, 0.22 to 0.86; P =.016). The occurrence of nonosseous metastases was similar (clodronate, n = 112; placebo, n = 128; P =.257), but there was a significant reduction in mortality (clodronate, n = 98; placebo, n = 129; P =.047) during the total follow-up period.\n Clodronate, given to patients with primary operable breast cancer, may reduce the occurrence of bone metastases, although this reduction was only significant during this medication period. There was a significant reduction in mortality.", "Patients with metastatic colorectal carcinoma (CRC) often develop bone metastases with a high risk of complications. Ibandronate is a novel single-nitrogen bisphosphonate that has been shown to be effective for treating bone metastases from breast cancer. A randomized, placebo-controlled trial was conducted to evaluate the efficacy and safety of ibandronate in patients with bone metastases from CRC. The primary efficacy end point was the proportion of patients with skeletal-related events (defined as pathologic fracture, spinal cord compression, radiation therapy to bone, change in antineoplastic therapy or surgery to bone). Secondary end points included time to first skeletal event, skeletal morbidity rate (events/year) and time to progression of bone lesions. In 73 patients with CRC, treatment with intravenous ibandronate 6 mg administered via a 15-min infusion significantly reduced the proportion of patients with skeletal events (39% vs. 78% with placebo; P = 0.019) and prolonged the time to first event by at least 6 months (median >279 vs. 93 days with placebo; P = 0.009). Ibandronate also significantly reduced the skeletal morbidity rate (mean 2.36 vs. 3.14 with placebo; P = 0.018) and prolonged time to progression of bone lesions (214 days vs. 81 days with placebo; P = 0.018). Ibandronate was well tolerated with very rare grade 3 or 4 toxicity. Furthermore, the incidence of renal adverse events was comparable with placebo and there were no clinically relevant changes in serum creatinine. Ibandronate provided significant clinical benefits for patients with bone metastases secondary to CRC. These results indicate that ibandronate may be an effective treatment for patients with metastatic bone disease following CRC. Larger studies are required for further assessment.", "PURPOSE AND PATIENTS: During the period from January 1990 to January 1996 a total of 953 patients with lymph node negative primary breast cancer were randomised to oral pamidronate (n=460) 150 mg twice daily for 4 years or no adjuvant pamidronate (n=493) in order to investigate whether oral pamidronate can prevent the occurrence of bone metastases and fractures. The patients received adjuvant chemotherapy, loco-regional radiation therapy, but no endocrine treatment.\n During the follow-up period the number of patients with pure bone metastases was 35 in the control group and 31 in the pamidronate group. The number of patients with a combination of bone and other distant metastases were 22 in the control group and 20 in the pamidronate group. The hazard rate ratio for recurrence in bone in the pamidronate group compared to the control group was 1.03 (95% confidence interval 0.75-1.40) and p=0.86. No effect was observed on overall survival. In a small subgroup of 27 patients from the study, 12 of whom were treated with pamidronate a significant bone preserving effect was observed on bone mineral density in the lumbar spine, but not in the proximal femur.\n The results from the trial do not support a beneficial effect of oral pamidronate on the occurrence of bone metastases or fractures in patients with primary breast cancer receiving adjuvant chemotherapy.", "Aromatase inhibitors (AIs) are accepted as adjuvant therapy for postmenopausal women (PMW) with hormone-responsive early breast cancer (EBC) with superior efficacy to tamoxifen. However, increased bone loss is associated with AIs.\n PMW with EBC receiving letrozole (2.5 mg/day for 5 years) were randomly assigned to immediate zoledronic acid (ZOL; 4 mg every 6 months) or delayed ZOL (initiated only for fracture or high risk thereof).\n Patients (N = 1065) had a median age of 58 years; 54% had received prior adjuvant chemotherapy. At 36 months, mean change in L2-L4 bone mineral density (BMD) was +4.39% for immediate versus -4.9% for delayed ZOL (P < 0.0001). Between-group differences were 5.27% at 12 months, 7.94% at 24 months, and 9.29% at 36 months (P < 0.0001 for all). At 36 months, the immediate-ZOL group had a significant 41% relative risk reduction for disease-free survival (DFS) events (P = 0.0314). Adverse events are consistent with the known safety profiles of the study drugs.\n At 36 months, immediate ZOL was more effective in preserving BMD during letrozole therapy. Immediate versus delayed ZOL led to significantly improved DFS. Benefits are observed in the context of a favorable, well-established safety profile for letrozole and ZOL.", "Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in patients with breast cancer. The aim of our study was to assess the effect of zoledronic acid on clearance of disseminated tumour cells (DTCs) from the bone marrow in women undergoing neoadjuvant chemotherapy for breast cancer.\n Patients were recruited for this open-label, phase 2 randomised trial between March 17, 2003, and May 19, 2006, at a single centre. Eligible patients had clinical stage II-III (> or = T2 and/or > or = N1) newly diagnosed breast cancer, Eastern Cooperative Oncology Group performance status of 0 or 1, and normal cardiac, renal, and liver function. 120 women were randomly assigned, using allocation concealment, to receive 4 mg zoledronic acid intravenously every 3 weeks (n=60), or no zoledronic acid (n=60), for 1 year concomitant with four cycles of neoadjuvant epirubicin (75 mg/m(2)) plus docetaxel (75 mg/m(2)) and two cycles of adjuvant epirubicin plus docetaxel. The primary endpoint was the number of patients with detectable DTCs at 3 months. Final analysis was done 1 year after the last patient was enrolled. Analyses were done for all patients with available data at 3 months. This study is registered with ClinicalTrials.gov, number NCT00242203.\n Of the 120 patients initially enrolled, one withdrew after signing consent and one patient's baseline bone marrow was not available. Both of these patients were in the control group. At 3 months, 109 bone-marrow samples were available for analysis. In the zoledronic acid group, bone marrow was not collected from one patient because of disease progression, one patient was taken off study because of severe diarrhoea, and two patients had not consented at the time of surgery. In the control group, bone marrow was not collected from two patients because of disease progression, one patient withdrew consent, and three patients were not consented at the time of surgery. At baseline, DTCs were detected in 26 of 60 patients in the zoledronic acid group and 28 of 58 patients in the control group. At 3 months, 17 of 56 patients receiving zoledronic acid versus 25 of 53 patients who did not receive zoledronic acid had detectable DTCs (p=0.054). The most common grade 3-4 toxicities were infection (five of 60 patients in the zoledronic acid group and six of 59 in the control group) and thrombosis (five of 60 in the zoledronic acid and two of 59 in the control group). There was one documented case of osteonecrosis in the zoledronic acid group.\n Zoledronic acid administered with chemotherapy resulted in a decreased proportion of patients with DTCs detected in the bone marrow at the time of surgery. Our study supports the hypothesis that the antimetastatic effects of zoledronic acid may be through effects on DTCs.\n Novartis Pharmaceuticals and Pfizer Inc.\n 2010 Elsevier Ltd. All rights reserved.", "Pamidronate therapy previously has been shown to reduce skeletal complications effectively for up to 12 months in breast carcinoma patients with bone metastases. The current study data provide further follow-up results regarding the effects of long term (up to 24 months) pamidronate treatment in women with breast carcinoma and osteolytic metastases.\n Follow-up results from two prospective, multicenter, randomized, double-blind, placebo-controlled intervention trials conducted at academic and community oncology centers were combined to provide a large data set with which to evaluate the long term efficacy and safety of pamidronate therapy. Seven hundred fifty-four women with Stage IV breast carcinoma and osteolytic metastases were randomized to the 2 treatment arms of the trial. Three patients were excluded from the intent-to-treat population for the analysis. A total of 751 evaluable patients were randomized to receive either a 90-mg intravenous pamidronate infusion (367 patients) or a placebo infusion (384 patients) every 3-4 weeks. The primary outcome measures were skeletal morbidity rate (events/year), proportion of patients developing a skeletal complication, and time to first skeletal complication.\n Of the 367 women receiving pamidronate, 115 (31.3%) completed the trial and 81 (22.1%) discontinued the study due to adverse events. Of the 384 women who received placebo, 100 (26.0%) completed the study and 76 (19.8%) discontinued the study due to adverse events. The skeletal morbidity rate was 2.4 in the pamidronate group and 3.7 in the placebo group (P < 0.001). In the pamidronate group, 186 of the 367 patients (51%) had skeletal complications compared with 246 of the 384 patients in the placebo group (64%) (P < 0.001). The median time to first skeletal complication was 12.7 months in the pamidronate group and 7 months in the placebo group (P < 0.001). Six patients treated with pamidronate discontinued treatment due to drug-related adverse events. Pain and analgesic scores were significantly worse in the placebo group compared with those patients in the pamidronate group.\n In the current study, monthly infusions of 90 mg of pamidronate as a supplement to antineoplastic therapy were found to be well tolerated and superior to antineoplastic therapy alone in preventing skeletal complications and palliating symptoms for at least 24 months in breast carcinoma patients with osteolytic bone metastases.\n Copyright 2000 American Cancer Society.", "Bisphosphonates have effectively reduced the development and progression of bone metastases in advanced breast cancer. The aim of this study was to determine whether bone metastases could be prevented by adjuvant clodronate treatment in patients with primary breast cancer.\n Between 1990 and 1993, 299 women with primary node-positive breast cancer were randomized to clodronate (n = 149) or control groups (n = 150). Clodronate 1,600 mg daily was given orally for 3 years. All patients received adjuvant therapy: premenopausal six cycles of CMF chemotherapy and postmenopausal antiestrogens (randomized to tamoxifen 20 mg or toremifene 60 mg/d for 3 years). Seventeen patients were excluded from the analyses because of major protocol violations. The final population was 282 patients. Intent-to-treat analyses were also performed for all major end points. The follow-up time was 5 years for all patients.\n Bone metastases were detected equally often in the clodronate and control groups: 29 patients (21%) versus 24 patients (17%) (P: = .27). The development of nonskeletal recurrence was significantly higher in the clodronate group compared with controls: 60 patients (43%) versus 36 patients (25%) (P: = .0007). The overall survival (OS) and disease-free survival (DFS) rates were also significantly lower in the clodronate group than in the controls (OS, 70% v 83%, P: = .009; DFS, 56% v 71%, P: = .007, respectively). In multivariate analyses, clodronate remained significantly associated with DFS (P: = .009).\n Adjuvant clodronate treatment does not prevent the development of bone metastases in node-positive breast cancer patients. However, clodronate seems to have a negative effect on DFS by increasing the development of nonskeletal metastases.", "Thirty-eight normocalcemic patients with bone metastases from breast carcinoma were randomized to receive dichloromethylene diphosphonate (CL2MDP) in addition to their specific antitumor treatment (chemotherapy and/or hormone therapy), at a dose of 300 mg/day/i.v. or placebo for the first 7 dys. The CL2MDP treatment then continued at a dose of 100 mg day/i.m. for 3 weeks and finally at 100 mg i.m. on alternate days for at least another 2 months. In both groups of patients there was a reduction in the intensity of pain (Scott-Huskisson analog), but there was a more frequent reduction in the daily consumption of analgesics in patients treated with CL2MDP (p = 0.02). Unlike the controls, the patients who received CL2MDP presented a significant reduction in urinary calcium (p = 0.003) and in hydroxyproline (p = 0.05) on the 7th day. As regards the clinical evolution, negative events such as the appearance of hypercalcemia, pathological fractures, new bone lesions or a substantial increase in the preexisting ones, were observed in 9 of the 12 evaluable patients treated with placebo and in 3 out of 9 treated with CL2MDP. Thickening of the preexisting osteolytic lesions was reported in 2 patients treated with CL2MDP. Tolerance was excellent: only a few patients complained of pain at the intramuscular drug injection site.", "Between March 1990 and May 1993 seventy three patients with previously untreated breast cancer, Stage III or IV without osseal metastases were randomized to sodium clodronate 1600 mg daily p.o.(arm A = 37 patients) or placebo (arm B = 36 patients) over 2 years, additionally to standard therapy. Ten patients were not evaluable for response because of short duration of therapy (less than 2 months). Bone metastases developed in 30% of patients in arm A and 23% patients in arm B. Median time to appearance of bone metastases was 13 months in arm A and 28 months in arm B. Non-bone metastases appeared in 48% patients in arm A and in 48% patients in arm B. Time to development of non-bone metastases was 20 months in arm A and 16 months in arm B. Five-year survival was 41% in arm A and 39% in arm B. There were no significant differences between the treated and control arms.", "Postmenopausal women with breast cancer receiving adjuvant aromatase inhibitors (AIs) are at risk for accelerated bone loss and subsequent fractures. The ongoing Zometa-Femara Adjuvant Synergy Trial (Z-FAST) is evaluating the efficacy and safety of zoledronic acid in preventing such bone loss.\n In this multicenter study, postmenopausal women with early hormone receptor-positive breast cancer receiving adjuvant letrozole were randomized to receive up-front or delayed-start zoledronic acid (ZA; 4 mg intravenously every 6 months) for 5 years. Delayed-start ZA was administered if the lumbar spine (LS) or total hip (TH) T score fell below -2.0 or a nontraumatic fracture occurred. The primary endpoint was to compare the change from baseline in LS bone mineral density (BMD) between groups at month 12; secondary endpoints, measured at other predetermined timepoints, included comparing changes in TH BMD, LS BMD, and markers of bone turnover, fracture incidence, and time to disease recurrence. Herein, we report the results of the 36-month interim analysis.\n Overall, 301 patients were randomized to each group. At month 36, the absolute difference in mean LS and TH BMDs between the up-front and delayed groups was 6.7% and 5.2%, respectively (P < .0001 for both). Although this study was not designed to show antifracture efficacy, the incidence of fractures was slightly higher in the delayed group (up-front, 17 [5.7%] vs. delayed, 19 [6.3%]) but not statistically significant (P = .8638). Pyrexia (27 [9%] vs. 6 [2%]; P = .0002) and bone pain (39 [13%] vs. 20 [6.7%]; P = .01) were more common in up-front patients; cough (13 [4.3%] vs. 27 [9%]; P = .03) was more common in delayed patients. No severe renal dysfunction or confirmed cases of osteonecrosis of the jaw were reported. Disease recurrence was reported in 9 up-front (3.0%) and 16 delayed (5.3%) patients (Kaplan-Meier analysis, P = .127), with an absolute decrease of 2.3%.\n Up-front ZA more effectively prevents AI-associated bone loss in postmenopausal women with early breast cancer than delaying therapy until substantial bone loss or fracture occurs.", "To investigate the effect of the bisphosphonate clodronate on the occurrence of skeletal events (hypercalcaemia, fractures and radiotherapy) in breast cancer patients with bone metastases.\n Prospective, randomized, controlled, clinical trial.\n A department of oncology in a university hospital.\n One hundred patients who received firstline systemic antineoplastic treatment for metastatic breast cancer with bone involvement were randomized to receive clodronate as two 400 mg capsules twice a day for 2 years or no additional therapy.\n In the clodronate group the number of skeletal events was reduced to 14 events in 48 evaluable patients as compared with 21 events in 51 evaluable control patients. The time to the first skeletal event was significantly longer in the clodronate group than in the control group (P = 0.015) and the most distinct difference was a lower occurrence of fractures in the clodronate group (P = 0.023). After 15 months the effect of clodronate tended to decline as the need for radiotherapy increased in the clodronate group compared with the control group (P = 0.069). Significant improvements in several quality-of-life aspects were seen in both groups during the first 6 months, but there was no significant difference between the groups. No effect was observed on time to radiologically evaluated disease progression in bone or on survival. The most frequent side-effects resulting in discontinuation of clodronate were nausea and diarrhoea.\n Oral clodronate is associated with a temporary reduction of morbidity related to bone metastases in breast cancer patients.", "One hundred forty-four patients with breast cancer and osteolytic bone metastases were randomized to receive either oral clodronate 1,600 mg/d (73 patients) or placebo (71 patients), in addition to either chemotherapy or hormonal therapy, for up to 12 months. Patients were withdrawn from the study when the 12 months of treatment had been achieve or a new bone event occurred, which was defined as: hypercalcemia (> 3 mmol/l), increase in, or onset of new bone pain due to metastases, requirement of radiotherapy for bone pain relief, pathological fractures (including vertebral collapse, spinal cord compression) or death due to bone metastases. Patients are well balanced according to age, performance status, bone condition, except for fractures, more frequent in the clodronate group (25% vs 12%). Of the 137 evaluable patients, 69 received oral clodronate and 68 placebo. Clodronate significantly delayed the median time to onset of new bone events compared to placebo, respectively 244 days and 180 days (p = 0.05). Hypercalcemia did not occur in the clodronate group but was observed in four placebo-treated patients. Clodronate-treated patients had a significant reduction in pain intensity compared to placebo (p = 0.01; measured using a visual pain scale) and significantly fewer patients receiving clodronate required analgesics (p = 0.02). The evaluation of global efficacy by physicians and patients indicated that clodronate was more efficacious than placebo (respectively p = 0.02 and p = 0.01). No significant difference in incidence of adverse effects was observed between the two groups. Clodronate therapy significantly delayed the occurrence of new bone events in these patients with bone metastases from breast cancer and adds to treatment of malignant osteolysis.", "The effect of pamidronate treatment on the first development of bone metastases was investigated in 124 patients with breast cancer, with either locally advanced disease (n = 33) or extraskeletal metastases (n = 91), but no bone metastases in a randomised, multicentre, open controlled study. Patients were assigned to treatment with oral pamidronate, 300 mg/day, (n = 65) or to a control group (n = 59). Tumour therapy was freely allowed. A first clinical event of skeletal morbidity occurred in 22% pamidronate and 20% control patients; unequivocal first radiological manifestation of bone metastases was found in 36% pamidronate and 27% control patients (n.s.). The actuarial risk of a first skeletal event was similar in both groups. Quality-of-life measurements of bone metastases-related aspects showed no differences between the two groups. 19 patients withdrew from the study because of gastrointestinal complaints attributed to pamidronate. We conclude that supportive oral pamidronate treatment (300 mg/day) does not prevent nor delay the development of bone metastases in breast cancer patients at risk." ]

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[ "[Bibliographic errors in Revista Española de Enfermedades Digestivas. A retrospective study of the year 1995].", "A review of the accuracy of references in the journal Emergency Medicine.", "Quality of abstracts in 3 clinical dermatology journals.", "Quotation accuracy in review articles.", "[Abstract quality assessment of articles from the Annales de Dermatologie].", "Accuracy of references in four pediatric nursing journals.", "Risk factors for citation errors in peer-reviewed nursing journals.", "Reference accuracy in Critical Care Medicine.", "Manuscript quality before and after peer review and editing at Annals of Internal Medicine.", "Trust, but verify. The accuracy of references in four anesthesia journals.", "Reporting of randomized clinical trial descriptors and use of structured abstracts.", "Citation and quotation accuracy in three anatomy journals.", "A survey of reference accuracy in five national dental journals.", "Accuracy of references in the orthopaedic literature.", "The accuracy of references in Anaesthesia.", "The quality of citations in major international obstetrics and gynecology journals.", "Accuracy of references in five leading medical journals.", "Accuracy of references in the pediatric surgery journals.", "Readers' evaluation of effect of peer review and editing on quality of articles in the Nederlands Tijdschrift voor Geneeskunde.", "The accuracy of references in Australian and New Zealand Medical Journals.", "How accurate are quotations and references in medical journals?", "Accuracy of referencing in the ophthalmic literature.", "Referencing and quotation accuracy in four manual therapy journals.", "[Errors in bibliographic references of Nefrología from 1981 to 1995. A quality control].", "Quality of nonstructured and structured abstracts of original research articles in the British Medical Journal, the Canadian Medical Association Journal and the Journal of the American Medical Association.", "Effects of peer review and editing on the readability of articles published in Annals of Internal Medicine.", "[Errors in literature references in the Nederlands Tijdschrift voor Geneeskunde].", "Do authors check their references? A survey of 500 references from the Journal of Oral and Maxillofacial Surgery.", "The accuracy of references in manuscripts submitted for publication.", "How accurate are references in clinical chemistry?", "Improvement of the accuracy of references in the Journal of Cardiothoracic and Vascular Anesthesia.", "References in Indian Pediatrics: authors need to be accurate.", "What is the quality of the reporting of research ethics in publications of nursing home research?", "Reference accuracy in the emergency medicine literature.", "A survey of reference accuracy in two Asian dermatologic journals (the Journal of Dermatology and the Korean Journal of Dermatology).", "Quality assessment of pharmacoeconomic abstracts of original research articles in selected journals.", "Quality of structured abstracts of original research articles in the British Medical Journal, the Canadian Medical Association Journal and the Journal of the American Medical Association: a 10-year follow-up study.", "Reference accuracy in neonatal-maternal nursing literature.", "[The structured summary: a tool for reader and author].", "Reference citation accuracy in theJournal of Anesthesia.", "[Errors in bibliographic references: a retrospective study in Medicina Clinica (1962-1992)].", "Can the accuracy of abstracts be improved by providing specific instructions? A randomized controlled trial.", "Accuracy of references in nursing journals.", "Effectiveness of a journal intervention to improve abstract quality.", "Accuracy of references in general readership nursing journals.", "Effect of including a clinical example on the ability of physical therapists to apply information in a technical research report.", "Accuracy of references in five biomedical informatics journals.", "[The accuracy of references in Turkish journals in orthopedics and traumatology].", "The accuracy of references in the Journal of Cardiothoracic and Vascular Anesthesia.", "Accuracy of data in abstracts of published research articles.", "The accuracy of references in the Hong Kong Medical Journal.", "Quotation accuracy in neuroanesthesiologic research.", "Reference accuracy in the dermatologic literature.", "Quotation and reference accuracy of three nursing journals.", "The practical effects of errors in reference lists in nursing research journals.", "A survey of the accuracy of references in 10 dental journals.", "Quotation accuracy: fact or fiction?", "Accuracy of references in three critical care nursing journals.", "How does the peer review process influence AANA journal article readability?", "Enhancement of hypoxemia by right-to-left atrial shunting in severe asthma.", "Do authors check their references? A survey of accuracy of references in three public health journals.", "Improvement of the accuracy of references in the Canadian Journal of Anaesthesia.", "Author, verify your references! Or, the accuracy of references in Israeli medical journals.", "Preliminary assessment of the effect of more informative (structured) abstracts on citation retrieval from MEDLINE.", "Structured abstracts in MEDLINE, 1989-1991.", "Reference citations in radiology: accuracy and appropriateness of use in two major journals.", "[Errors in bibliographic references in the Revista Española de Anestesiología y Reanimación: retrospective study of 1994].", "The accuracy of references in paediatric journals.", "Accuracy of references in Anesthesia & Analgesia does not improve.", "The accuracy of references of three allergy journals.", "Improvement of the accuracy of references in Anesthesiology.", "How accurate are references in the Australian and New Zealand Journal of Surgery?", "The accuracy of citation and quotation in otolaryngology/head and neck surgery journals." ]

[ "To determine the accuracy of bibliographic citation in Revista Española de Enfermedades Digestivas (REED) and compare it with other Spanish and international journals.\n We reviewed all 1995 volumes of the REED and randomly selected 100 references from these volumes. Nine citations of non-journal articles were excluded and the remaining 91 citations were carefully scrutinized. Each original article was compared for author's name, title of article, name of journal, volume number, year of publication and pages.\n Some type of error was detected in 61.6% of the references and on 3 occasions (3.3%) impeded finding to the original article. Errors were found in authors (37.3%); article title (16.4%), pages (6.6%), journal title (4.4%), volume (2.2%) and year (1%). A single error was found in 42 citations, 2 were found in 13 and 3 were found in 1.\n REED's rate of error in references is comparable to the rates of other spanish and international journals. Authors should exercise more care in preparing bibliographies and should invest more effort in verification of quoted references.", "To assess the accuracy of references in articles published in Emergency Medicine, and to categorize these errors.\n All the references in Volume 12 of Emergency Medicine were listed and numbered consecutively. A sample of 100 references was then selected. Each reference was then checked, initially on an electronic database, with the original article being used as the gold standard.\n 1469 citations were included in the study. A random sample of 100 was taken and examined in detail. 35 papers were shown to have at least one error, and a total of 41 errors were found. The maximum number of errors in one paper was 3. These errors are analysed in detail.\n Poor reference accuracy is a common problem in medical literature, and Emergency Medicine is not immune to these failings. Authors need to take more care to ensure that the accuracy of citations improves.", "Structured abstracts have been widely adopted in medical journals, with little demonstration of their superiority over unstructured abstracts.\n To compare abstract quality among 3 clinical dermatology journals and to compare the quality of structured and unstructured abstracts within those journals.\n Abstracts of a random sample of clinical studies (case reports, case series, and reviews excluded) published in 2000 in the Archives of Dermatology, The British Journal of Dermatology, and the Journal of the American Academy of Dermatology were evaluated. Each abstract was rated by 2 independent investigators, using a 30-item quality scale divided into 8 categories (objective, design, setting, subjects, intervention, measurement of variables, results, and conclusions). Items applicable to the study and present in the main text of the article were rated as being present or absent from the abstract. A global quality score (range, 0-1) for each abstract was established by calculating the proportion of criteria among the eligible criteria that was rated as being present. A score was also calculated for each category. Interrater agreement was assessed with a kappa statistic. Mean +/- SD scores were compared among journals and between formats (structured vs unstructured) using analysis of variance.\n Mean quality scores of abstracts by journal and by format.\n Interrater agreement was good (kappa = 0.71). Mean +/- SD quality scores of abstracts were significantly different among journals (Archives of Dermatology, 0.78 +/- 0.07; The British Journal of Dermatology, 0.67 +/- 0.17; and Journal of the American Academy of Dermatology, 0.64 +/- 0.15; P =.045) and between formats (structured, 0.71 +/- 0.11; and unstructured, 0.56 +/- 0.18; P =.002). The setting category had the lowest scores.\n The quality of abstracts differed across the 3 tested journals. Unstructured abstracts were demonstrated to be of lower quality compared with structured abstracts and may account for the differences in quality scores among the journals. The structured format should be more widely adopted in dermatology journals.", "The purpose of this study was to determine the accuracy of referenced statements in review articles focused on drug therapy. Review articles published between January and December 1987 in Clinical Pharmacy, DICP, Drugs, and Pharmacotherapy were used. Ninety-nine references from these articles were randomly selected and pulled to determine if the published study results were in agreement with the review article statement. These references accounted for 165 statements. Thirty-nine of 165 statements in the review articles (24 percent) were found to be inappropriate when compared with the original references. These inappropriate quotations were classified as either wrong, misleading, or deriving from only the discussion section of the original article. There is a need for increased awareness by authors to differentiate between reported results, article hypothesis, and their own interpretations, as well as for accuracy in quotation.", "Article's abstracts are an important part of the publication, widely available in electronic databases. We assessed the quality of abstracts in the Annales de Dermatologie. The main objective was to compare abstract quality in 3 periods in the past decade. In this Journal, structured abstracts are required since 1993. The secondary objective was to compare structured and non structured abstract quality.\n Three periods were assessed: 1991-92, 1996 and 2000. We selected the abstracts of original studies, excluding non focused descriptive case series. We used a criteria scale elaborated by Narine et al. Thirty criteria were assessed for each abstract, divided into 8 categories: purpose, research design, setting, subjects, intervention, outcome measurement, results and conclusion. If applicable to the study, a criterion was rated 1 (present) or 0 (absent). The final score for each abstract was defined as the ratio of positive answers among rated criteria. Mean scores for each period were compared using analysis of variance (mean +/- standard deviation). The temporal trend was calculated by simple linear regression. The mean scores of structured and unstructured abstracts were also evaluated and then compared.\n For each period, chronologically, 8, 17 and 18 (total 43) abstracts were evaluated. Mean scores for each period were 0.72 +/- 0.20 (1991-92); 0.69 +/- 0.12 (1996) and 0.83 +/- 0.08 (2000). These 3 scores were significantly different (P=0.006), with a trend toward increasing (Regression coefficient R(2)=0.136; P=0.015). Research setting obtained the lowest score (0.4). Structured (0.72 +/- 0.20; n=35) and non structured abstracts (0.76 +/- 0.12; n=8) were not significantly different.\n Abstracts of articles published in the Annales de Dermatologie contained on average 3/4 of the required informative items. The trend toward better scores may be explained by an increased attention of the editorial board as well as authors and reviewers. The quality could be improved by systematically mentioning the research setting.", "Inaccurate references hinder retrieval of documents, may prevent researchers from examining all of the work by an author, and may result in authors not getting credit for their work. This study determines the number and types of errors in references in four widely read pediatric nursing journals. Of the 190 references examined, 79 of them contained an error, for an overall error rate of 41.6%. Major errors, which prevent the rapid retrieval of information, occurred in 28.9% of the references. Minor errors occurred at half the rate (13.7%) of major errors. Errors in the titles of articles, chapters, and books were the most common type of mistake followed by errors in authors' names.\n Copyright 2001 by W.B. Saunders Company", "Citation errors are common among nursing journals. But, there are no data regarding the factors that predispose to these errors.\n To determine the risk factors that predispose to citation error in peer-reviewed nursing journals.\n Five hundred and fifty references were selected randomly from articles published in eleven nursing journals for the year 1998. The incidences of major and minor citation errors were determined by comparing with the original articles. The relative odds of citation errors for the number of authors, collaborating institutions and the length of the reference list were calculated. The correlation between the scientific quality of the journal (by means of journal impact factor and immediacy index) and the incidence of citation error were also determined.\n The incidence of citation errors is comparable to those reported previously. Long reference lists in articles written by a single author predicted strongly the occurrence of minor citation errors. Journals with a high impact factor and immediacy index tend to contain fewer minor mistakes. None of these factors affect the incidence of major errors.\n Contributors to journals should be aware of the various risk factors for citation errors. Citation accuracy may be improved by modifying these factors.", "nan", "To evaluate the effects of peer review and editing on manuscript quality.\n Editorial offices of Annals of Internal Medicine.\n Masked before-after study. MANUSCRIPTS: 111 consecutive original research manuscripts accepted for publication at Annals between March 1992 and March 1993.\n We used a manuscript quality assessment tool of 34 items to evaluate the quality of the research report, not the quality of the research itself. Each item was scored on a 1 to 5 scale. Forty-four expert assessors unaware of the design or aims of the study evaluated the manuscripts, with different persons evaluating the two versions of each manuscript (before and after the editorial process).\n 33 of the 34 items changed in the direction of improvement, with the largest improvements seen in the discussion of study limitations, generalizations, use of confidence intervals, and the tone of conclusions. Overall, the percentage of items scored three or more increased by an absolute 7.3% (95% CI, 3.3% to 11.3%) from a baseline of 75%. The average item score improved by 0.23 points (CI, 0.07 to 0.39) from a baseline mean of 3.5. Manuscripts rated in the bottom 50% showed two- to threefold larger improvements than those in the top 50%, after correction for regression to the mean.\n Peer review and editing improve the quality of medical research reporting, particularly in those areas that readers rely on most heavily to decide on the importance and generalizability of the findings.", "To determine the accuracy of bibliographic citation in the anesthesia literature, we reviewed all 1988 volumes of ANESTHESIOLOGY, Anesthesia and Analgesia, British Journal of Anaesthesia, and Canadian Journal of Anaesthesia and sequentially numbered all references appearing in that year (n = 22,748). One hundred references from each of the four journals were randomly selected. After citations to nonjournal articles (i.e., books or book chapters) were excluded, the remaining 348 citations were analyzed in detail. Six standard bibliographic elements--authors' names, article title, journal title, volume number, page numbers, and year--were examined in each selected reference. Primary sources were reviewed, unless our institution did not own the source or could not obtain it through interlibrary loan, in which case standard indexes, abstracting services, and computerized databases were consulted. Each element was checked for accuracy, and references were classified as either correct or incorrect. A reference was correct if each element of the citation was identical to its source. Of the examined references, more than half (50.3%) contained an error in at least one element. The elements most likely to be inaccurate were, in descending order, article title, author, page numbers, journal title, volume number, and year. No significant differences (P = 0.283) existed in the error rates of the four journals; the percentage of citations containing at least one error ranged from 44% (Anesthesia and Analgesia) to 56% (British Journal of Anaesthesia). The citation error rate of anesthesia journals is similar to that reported in other specialties, where error rates ranging from 38% to 54% have been documented.", "Structured abstracts, that is, abstracts that describe a study using requisite content headings, provide more informative content. Concomitant reporting in the text of the report might improve with structured abstract use because of increased awareness by authors or editors of important study areas associated with content headings.\n To assess whether structured abstract use is associated with improved reporting of randomized clinical trials.\n Survey of trial reports published the year preceding, of, and following new use of structured abstracts, found by hand searching Archives of Ophthalmology (1992-1994) and Ophthalmology (1991-1993), as well as trial reports published concurrently without change in abstract format (American Journal of Ophthalmology, 1991-1994).\n We measured the inclusion of 56 criteria derived from Consolidated Standards of Reporting Trials (CONSORT) descriptors (JAMA 1996;276:637-639) in the text of each report and calculated the number of criteria included per report and the proportion of reports including individual criteria. Reports with structured abstracts were compared with those without, and reports published in 1993 and 1994 in the American Journal of Ophthalmology were compared with those published in 1991 and 1992.\n The mean (SEM) number of criteria included by authors was 15.8 (0.4) per report in 125 trial reports. We found no difference in the mean number of criteria included or the proportion of reports that included specific criteria by journal. Following structured abstract use, there was no difference in either the mean number of criteria per report or the proportion of reports including a majority of criteria within each CONSORT subheading. Four criteria were included more often and 2 less often following structured abstract use in individual journals.\n Using CONSORT descriptor criteria to evaluate reporting quality, we found no difference in text reporting associated with structured abstract use in the journals examined.", "Citation and quotation errors are common in medical journals. We assessed the prevalence of those errors in gross anatomy journals, where articles often cite old anatomical studies. The study included 199 randomly selected references from articles published in the first 2001 issue of three major gross anatomy journals: Annals of Anatomy, Clinical Anatomy, and Surgical and Radiologic Anatomy. The selected references were checked for accuracy against the original articles. Citation errors were classified as major, intermediate, and minor. Quotation errors were classified as major and minor. Citations errors were found in 27% (54/199) of the references and 38% of them were major errors. Errors occurred in 19% (52/272) of quotations and nearly all (94%) were major. Furthermore, 24% of the quotations were indirect references to a secondary, instead of original, source. There was no statistically significant difference in the rates of citation or quotation errors between the references published before or after the introduction of MEDLINE (chi2 test, P > 0.05) in 1963, and the prevalence of these errors in gross anatomy journals was similar to that found in other medical fields. A high proportion of major citation errors, a very high proportion of major quotation errors, and the substantial number of indirect quotations call for serious editorial action in anatomy journals.\n Copyright 2004 Wiley-Liss, Inc.", "Previous studies have examined the bibliographic accuracy of citations in medical journals. The purpose of this study was to assess reference accuracy in five national dental journals. One hundred references were randomly selected from the March, 1987, issue of each of five dental journals (a total of 500 references). Each reference was verified either from the original source or from other indexing tools if the original was unavailable. References were divided into two categories: incorrect and correct. The number of incorrect references was counted and subdivided into major and minor errors. The errors were grouped by types of error: author, article title, citation (which included errors in journal title, volume, issue, and page numbers), and \"unable to verify\". This survey found 211 (42%) inaccuracies out of 500 references reviewed, with a total of 248 errors within the incorrect group. Out of the latter, 173 (70%) were minor errors, and 75 (30%) were major errors. Types of minor errors ranked as follows: minor article title errors, 86 (35%); minor author errors, 61 (25%); and minor citation errors, 26 (10%). Types of major errors were ranked as follows: incorrect journal citation, 32 (13%); \"unable to verify\", 25 (10%); incorrect author, 10 (4%); and incorrect article title, 8 (3%). The results of this survey showed that nearly half of the references reviewed were inaccurate.", "nan", "We reviewed all the references quoted in Volume 45 (1990) (n = 3967) and half the references quoted in Volume 49 (1994) (n = 2183) of Anaesthesia. The references were numbered sequentially and 100 references from each year were randomly selected. Citations of non-journal articles were omitted leaving 197 citations for careful scrutiny. The authors' names, article title, journal title, volume number, page numbers, and year were examined in each selected reference. A reference was deemed correct if each element of the citation was identical to its source. Of the references examined, 32% and 41% contained one or more errors in 1990 and 1994, respectively. The elements most likely to be inaccurate were, in descending order of frequency, article title, author, and page number. There was no significant difference in the error rate between the 2 years. It is the responsibility of contributors to ensure that all references are carefully checked.", "Our goal was to determine the error rate in references in articles published in three major international journals in obstetrics and gynecology.\n All issues (excluding supplements) for the year 1995 of the American Journal of Obstetrics and Gynecology, the Australian and New Zealand Journal of Obstetrics and Gynaecology, and the British Journal of Obstetrics and Gynaecology were examined. References were numbered sequentially, and 50 randomly selected references from each journal were checked against the original for accuracy.\n Errors were found in the majority of references. The lowest error rate was 55.6% from the Australian and New Zealand Journal of Obstetrics and Gynaecology, and the highest was 66.7% from the British Journal of Obstetrics and Gynaecology. The difference between journals was not statistically significant. The most frequent types of error were in the title of the article or in the authors' names.\n Error rates in major international journals in obstetrics and gynecology are high, and care must be taken by authors and journal staff to improve the quality of published articles.", "nan", "nan", "Academic biomedical journals use peer review and editing to help to select and improve the quality of articles. We have investigated whether articles accepted by the Nederlands Tijdschrift voor Geneeskunde, the Dutch Journal of Medicine, were improved after peer review and editing (post-acceptance scientific and copy editing).\n 400 readers of the journal (100 each of medical students, recent medical graduates, general practitioners, and specialists) were invited to participate in a questionnaire survey. The first 25 from each group who agreed to participate were included. We posted a pack containing a set of identically appearing typescripts (ie, blinding) of the submitted, accepted, and published versions of 50 articles that had been published in Ned Tijdschr Geneeskd. Each evaluator received two of the sets of versions, and each set was evaluated by one person from each group. The package also included two questionnaires: the first was used to compare the submitted with the accepted version (25 questions), the second compared the accepted with the published version (17 questions). The questions were answered on five-point scales, and were about the quality of the articles or were general/overall scores. We analysed the data as scores of 3-5 (ie, improvement) versus 1-2.\n After peer review, the quality in 14 of 23 questions (61%) was significantly improved (p = 0.03 or smaller). In particular, the overall score and general medical value were significantly improved (p = 0.00001 for each). Editing led to significant improvement in 11 of 16 questions (69%, p = 0.017 or smaller), and especially in style and readability (p = 0.001 and p = 0.004). Generally, we found no differences between the scores of the four categories of evaluators. 72% of the evaluators correctly identified which version was which.\n Evaluations by readers of the Ned Tijdschr Geneeskd indicated significant improvement of published articles after both peer review and editing. We think that peer review and editing are worthwhile tasks. We also think that possible biases would have had a negligible effect on our results (including the fact that we selected the first 25 evaluators who responded, that some evaluators may have read the published version, and that one questionnaire may have looked more scientific than the other, more editorial one).", "Previous studies have found high error rates in references in biomedical journals. The aim of this paper was to assess the accuracy of references in three Australian and New Zealand general medical journals.\n References from the August 1999 issues of the Medical Journal of Australia, the New Zealand Medical Journal and the Australian and New Zealand Journal of Medicine were assessed for accuracy using PubMed of the National Library of Medicine.\n This study found a high rate of reference errors in Australian and New Zealand medical journals. The reference error rate ranged from 33.5 to 48.8%. The most frequent errors were in the author's names and in the title.\n The reference error rate in Australia and New Zealand medical journals is high and is preventable. Authors should be more diligent and preferably verify cited references against the original article.", "The accuracy of quotations and references in six medical journals published during January 1984 was assessed. The original author was misquoted in 15% of all references, and most of the errors would have misled readers. Errors in citation of references occurred in 24%, of which 8% were major errors--that is, they prevented immediate identification of the source of the reference. Inaccurate quotations and citations are displeasing for the original author, misleading for the reader, and mean that untruths become \"accepted fact.\" Some suggestions for reducing these high levels of inaccuracy are that papers scheduled for publication with errors of citation should be returned to the author and checked completely and a permanent column specifically for misquotations could be inserted into the journal.", "To investigate the frequency of citation and quotation errors in the ophthalmic literature.\n Analysis of 200 references from 100 papers published in 10 ophthalmic journals.\n A sample of 20 references was randomly selected from each of the 10 journals and each reference was checked for accuracy. Quotations were categorized as totally, partially, or not accurate.\n There were 35 citation errors in 32 references, only four of which were errors in PubMed. Thirty quotations of references were not accurate; 20 were partially accurate.\n Citation and quotation errors are relatively common within the ophthalmic literature. This may be improved through technical editing.", "The aim of the study was to investigate the reference and quotation accuracy in four peer-reviewed manual therapy journals. A stratified random sample of original research (n=7) was collected from each of the journals spanning the years January 2000 to December 2001. A further random selection of 80 references from each journal paper sampled was then reviewed (Total N=320) for citation and quotation accuracy. Numbers of citations with errors were determined, then classified as either major or minor and categorized by bibliographic headings (author, title, journal, year, volume, page and irretrievable). Each quotation was individually assessed for accuracy and judged to be either correct or incorrect. A quotation was deemed correct if it accurately substantiated and reported the original authors assertions. One hundred and fifteen citations across all journals contained errors (35.9%). Some citations exhibited multiple major and minor errors. Bibliographically classified errors for all journals showed 61 author, 51 title, 6 journal, 4 year, 12 volume and 25 page errors. JMPT showed the lowest referencing error rate (20%) while JBWMT recorded the highest (58.8%). The total number of quotation errors across all journals was 69 (12.3%). JMPT showed the lowest quotation error rate of 6 (4.7%), MT had 12 errors (7.3%), JOM produced 21 errors (13.3%), while JBWMT recorded the highest error rate with 32 (27.6%). Poor citation and quotation is a reflection on the scholarly work of the authors and the journal. The trend for errors in quotation is more worrying than citation errors as it reflects poor diligence on the part of the investigators.", "The accuracy of the reference list is considered an essential factor in determining the quality of a scientific publication, and has been reviewed and published in several medical journals. The rate of citation errors in NEFROLOGIA has not been published before. The aim of this study has been to examine the accuracy of the references citation in the numbers of the journal published for a period of 15 years, from the first issue in 1981 to the last one on 1995.\n In this period 68 ordinary issues of the journal were published, with 520 original articles that constituted the data base, 87 articles were selected applying a table of random numbers with 5 references of each article selected to be reviewed with a total of 435. The accuracy of the name of the authors, title of the article, volume, initial and last page and year of publication were evaluated, accordingly with the NEFROLOGIA normative. Citation errors were considered major or minor depending on whether they prevented or not the immediate retrieval of the article listed.\n Of the 435 citations examined, 433 could be located, being impossible in 2 with the data supplied. In 189 (43.45%) 237 errors were detected, with 13.50% of them being considered major and 86.50% minor, with the greatest percentage of errors occurring in the data about the authors of the articles referenced 96 (40.50%).\n The issues of NEFROLOGIA published in this period present a high number of bibliographic reference errors, being the rate similar to other evaluated scientific periodical journals. This fact should be improved, and authors and reviewers should thoroughly check their references in order to avoid these mistakes, as they affect the quality standard of the publication.", "To assess and compare the quality of nonstructured and structured abstracts of original research articles in three medical journals.\n Blind, criterion-based observational study.\n Random sample of 300 abstracts (25 abstracts per journal each year) of articles published in the British Medical Journal (BMJ), the Canadian Medical Association Journal and the Journal of the American Medical Association (JAMA) in 1988 and 1989 (nonstructured abstracts) and in 1991 and 1992 (structured abstracts).\n The quality of abstracts was measured against 33 objective criteria, which were divided into eight categories (purpose, research design, setting, subjects, intervention, measurement of variables, results and conclusions). The quality score was determined by dividing the number of criteria present by the number applicable; the score varied from 0 to 1.\n The overall mean quality scores for nonstructured and structured abstracts were 0.57 and 0.74 respectively (p < 0.001). The frequency in meeting the specific criteria was generally higher for the structured abstracts than for the nonstructured ones. The mean quality score was higher for nonstructured abstracts in JAMA than for those in BMJ (0.60 v. 0.54, p < 0.05). The scores for structured abstracts did not differ significantly between the three journals.\n The findings support recommendations that promote the use of structured abstracts. Further studies should be performed to assess the effect of time on the quality of abstracts and the extent to which abstracts reflect the content of the articles.", "To measure the effect of the peer review and editorial processes on the readability of original articles.\n Comparison of manuscripts before and after the peer review and editorial processes.\n Annals of Internal Medicine between March 1 and November 30, 1992. MANUSCRIPTS: One hundred one consecutive manuscripts reporting original research.\n Assessment of readability by means of two previously validated indexes: the Gunning fog index (units of readability in the fog index roughly correlate to years of education) and the Flesch reading ease score. Each manuscript was analyzed for readability and length on receipt and after it had passed through the peer review and editorial processes. Text and abstracts were analyzed similarly but separately. Mean readability scores were compared by two-tailed t tests for paired observations.\n Mean (+/- SD) initial readability scores of manuscripts and abstracts by the Gunning fog index were 17.16 +/- 1.55 and 16.65 +/- 2.80, respectively. At publication, scores were 16.85 +/- 1.42 and 15.64 +/- 2.42 (P = .0005 and P < .0001 for before-after differences, respectively). By comparison, studies of other print media showed scores of about 11 for the New York Times editorial page and about 18 for a typical legal contract. Similar changes were found for the Flesch scores. The median length of the manuscripts increased by 2.6% and that of the abstracts by 4.2% during the processes.\n The peer review and editorial processes slightly improved the readability of original articles and their abstracts, but both remained difficult to read at publication. Better readability scores may improve readership.", "Literature references contain a considerable number of inaccuracies, both in citations and in quotations. We investigated the accuracy of quotations and references in Nederlands Tijdschrift voor Geneeskunde. We checked at random 100 references of articles presented for publication during a period of 4 weeks using Index Medicus. The citation and quotation of another 100 references (50 with a reading list of less than 13, and 50 with a reading list of more than 24 articles) of published original articles were checked, using the original article. In the references of articles presented for publication 70% contained one or more inaccuracies. In the published articles 31% was not completely correct. In 5% these errors prevented immediate identification of the cited article. In one of every three articles a citation error was made: 5 trivial errors, 16 slightly misleading and 12 seriously misleading errors were found. We could not find a relation between the number of citation errors and the length of the reading list. The original source was not cited in 8 articles. Our conclusion is that the number of inaccuracies, in references as well as in citations, is high; authors should check this part of their articles more carefully. Notably the use of multiple references after a sentence with a number of statements is to be avoided.", "From a systematic study of 500 references randomly selected in the January through July, 1992, issues of the Journal of Oral and Maxillofacial Surgery, it was found that 26% had errors. 6.2% of the referenced articles could not be found at all; either due to the fact that they were obscure foreign articles, their age made it difficult to verify, they cited non-peer reviewed journals, or the references cited journals that possibly did not exist. The remaining references were verified either from the original source or from other indexing tools if the original was not available.", "To analyze the errors present in references cited in papers submitted for peer review for possible publication.\n Nineteen consecutive manuscripts submitted for peer review were assessed. They contained a total of 261 references. Manuscripts were submitted to 1 of 5 major radiology journals. Journal references were compared with either the original articles or abstracts obtained through MEDLINE. Book references were checked against the original book. In total, 259 of 261 references were obtained. The remaining 2 references were both out-of-print books that were not available. Each reference was checked and errors were identified as either major or minor, depending on the gravity of the error. Errors were analyzed to see whether they could be attributed to not adhering to journal guidelines or to other reasons.\n Of a total of 259 references, 56% (n = 145) contained at least 1 error, 53% (n = 137) contained minor errors and 15% (n = 39) contained major errors. Five per cent (n = 13) of references had more than 3 errors, and 79% (n = 274) of all errors were the direct result of authors not following journal instructions.\n Over half of all references included in manuscripts submitted to radiology journals contain at least 1 error. The majority are avoidable, resulting from failure to follow the journal's instructions to authors.", "nan", "nan", "To determine the accuracy of references published in Indian Pediatrics, we reviewed the reference lists appended to the original articles published in Indian Pediatrics during the year 2002 (volume 39) for citation and quotation accuracy. A total of 176 references out of 322 cited in 17 original articles could be retrieved from available resources. Errors of citation were found in 69 (39.27 percent) references while errors of quotation were found in 15 (8.6 percent) references. The most common errors were those in the name of authors and title of the article. Contributors should make serious efforts to check the accuracy of the references cited in their manuscripts.", "To assess the quality of reporting of research ethics in published clinical research that involves a particularly vulnerable population: nursing home residents.\n A structured review of publications researched from 1992 to 1996 that involve nursing home residents. The review instrument assessed each publication's compliance with four common standards for research that involves nursing home residents or the cognitively impaired: justification of the use of nursing home residents, Institutional Review Board (IRB) review, nursing home committee review, and informed consent. For each publication, these results were summed into a quality score. The research ethics requirements contained in the journals' instructions for authors that corresponded with each publication were categorized in order to compare whether an association exists between the average quality score for each category and the detail of its research ethics instructions.\n Forty-five publications were identified. The four quality measures of research ethics showed that (1) all 45 publications reported justification of use of nursing home residents, (2) 36 publications reported that informed consent was obtained or waived, (3) 18 publications reported IRB review, and (4) six publications reported nursing home committee review. Of the 35 publications reporting informed consent was obtained, 16 reported assessing subjects' decisional capacity, and 24 reported whether cognitively impaired subjects were included (19) or excluded (5). The research ethics requirements of each publication's instructions for authors ranked it in one of four categories: (A) None (9); (B) Less than \"Uniform Requirements (UR) for Manuscripts Submitted to Biomedical Journals\" (7); (C) UR (24); (D) UR plus Additional Instructions (5). A positive association exists between the detail of a research ethics instructions category and the average research ethics quality score for each category (Kruskal-Wallis chi2 = 11.2, P = .01). That is, the more detailed the instructions, the greater the quality score.\n In publications of research that involves nursing home residents, basic standards of research ethics are not typically reported. However, the positive association between research ethics instructions category and research ethics quality score suggests that a journal's instructions for authors or other features of peer review and editing can affect the quality of reporting research ethics.", "To determine the incidence and nature of errors in the citation and quotation of references contained in the emergency medicine literature.\n A retrospective analysis of a random sample of articles and references found in the three major emergency medicine journals.\n A university/county hospital.\n We examined single issues of three emergency medicine journals: Annals of Emergency Medicine, Journal of Emergency Medicine, and American Journal of Emergency Medicine.\n None.\n Four independent reviewers assessed 145 references from 46 referring authors for citational and quotational accuracy.\n Major and minor citation errors were found in 10.3% and 17.2% of reference listings, respectively. Qualitative quotational errors were found in 35.2% of references. Eighty-two percent of these errors were considered to be major. Quantitative quotational errors were found in 47% of references reviewed. Secondary rather than primary reference sources were used in 41.4% of references reviewed.\n This study demonstrates a substantial error rate in the citation and quotation of reference sources in the emergency medicine literature. In addition, verification of primary source material was not done by a large percentage of the authors reviewed. Recommendations for improving the accuracy of the emergency medicine literature are offered.", "The reference list is an important part of a scientific article. To be useful, it must be accurate.\n To evaluate the reference accuracy in the Journal of Dermatology and the Korean Journal of Dermatology, we randomly selected 100 references from each journal and checked them against the original articles.\n The overall rate of citation errors was 24% in the Journal of Dermatology and 33% in the Korean Journal of Dermatology. Errors in the title and author names were common, each occurring in about half of the citation errors. The overall rate of quotation errors was 14% in the Journal of Dermatology and 27% in the Korean Journal of Dermatology.\n This study shows that the rate of citation errors is unacceptably high in the Journal of Dermatology and the Korean Journal of Dermatology, which significantly diminishes the value of the reference list. We would strongly urge that the peer review of citation and quotation accuracy should be strengthened.", "To assess and compare the quality of pharmacoeconomic abstracts of cost-minimization analyses, cost-effectiveness analyses, cost-utility analyses, and cost-benefit analyses of original research articles in selected medical, pharmacy, and health economics journals.\n MEDLINE was used to identify articles in selected medical, pharmacy, and health economics journals using the MeSH word \"economic\" and text words \"cost\" and \"pharmacoeconomic\"; the journal PharmacoEconomics was searched manually. All retrieved abstracts were evaluated. Original, comparative (at least one drug comparator) research articles (1990-1994) reporting both costs and clinical outcomes were included in the quality analysis. Abstract quality was assessed as a percentage by using a checklist with 29 objective criteria. Group consensus produced interrater reliability greater than 0.8.\n One thousand two published abstracts labeled with the above key words were identified. Of these, 951 were excluded from quality assessment because they were not original research (18%), were not pharmacoeconomic research (47%), lacked a drug comparator (35%), or did not report a clinical outcome (0.5%). Thus, the quality of 51 (5% of the total) remaining abstracts was assessed. Overall scores were 56% in 1990 and 58% in 1994 (p = 0.094). Medical articles scored highest (61.5%; n = 25), pharmacy articles were next (54.3%; n = 5), and health economics articles were lowest (53.4%; n = 21) (p = 0.091); structured abstracts scored significantly higher (62.5%; n = 20) than unstructured (53.3%; n = 31) (p = 0.003).\n Abstract quality was generally poor, with no significant change in quality over time. Medical journals scored highest, probably because they use structured abstracts. Guidelines for structured pharmacoeconomic abstracts may assist in improving quality.", "We compared the quality of structured abstracts of original research articles from the British Medical Journal (BMJ), Canadian Medical Association Journal (CMAJ), and the Journal of the American Medical Association (JAMA) from 1991 to 1992 and 2001 to 2002 between journals.\n A random, stratified sample of 54 abstracts from 2001 to 2002 in BMJ, CMAJ, and JAMA was compiled and coded. Two blinded raters reviewed 27 abstracts each against 33 objective criteria, separated into eight categories (purpose, research design, setting, subjects, intervention, measurement of variables, results, and conclusion). The quality score was the proportion of criteria present (range = 0-1).\n The overall mean quality score (0.74) for 2001-2002 was significantly higher than the 1988-1989 unstructured abstracts (mean = 0.57; p<0.001) but not different from the 1991-1992 structured abstracts (mean = 0.74; p>0.05). In 2001-2002, abstracts of CMAJ and JAMA (both means = 0.76) improved significantly over 1991-1992 (p<0.05) and scored significantly higher than BMJ (mean = 0.71; d.f. = 16, p<0.05). Some individual criteria scores (intervention, statistical information) improved but information was found consistently under-represented in areas that imply shortcomings of the studies.\n We found a consistency in abstract quality regardless of the precise format used by different journals. This indicates that the framework for research articles already in place should be maintained and further modification of the framework may not necessarily improve the abstract quality.", "To identify the frequency and types of reference errors in neonatal-maternal nursing literature. This study was an extension of earlier research on reference accuracy in pediatric and critical care nursing journals.\n A random sample was selected of references in three nursing journals: Neonatal Network: The Journal of Neonatal Nursing; Journal of Obstetric, Gynecologic, and Neonatal Nursing; and The American Journal of Maternal/Child Nursing. References were compared against original publications, and errors were classified as major or minor based on criteria used in earlier studies.\n Fifty-four of the 221 references had errors, for an overall error rate of 24.4 percent. Major errors were found in 21.3 percent of the references, and minor errors were calculated at 3.2 percent. Errors in the author's name were most common, followed by errors in titles of articles and books. The rates of reference errors in this study were lower than those reported previously in the nursing and medical literature.", "To determine and to compare the information contained in structured abstracts in original articles in Annals of Internal Medicine (AIM), British Medical Journal (BMJ), New England Journal of Medicine (NEJM) and of abstracts that have been published in Nederlands Tijdschrift voor Geneeskunde (NTvG).\n Editorial office NTvG.\n Descriptive.\n Critical reading of 15 original articles of AIM (5), BMJ (5) and NEJM (5) in 5 consecutive issues starting from 1 March 1990 and all original articles of 6 consecutive issues of NTvG starting from 7 april 1990. According to the criteria of the 'ad hoc working group for critical appraisal of the medical literature' the amount of information in all foreign abstracts and 10 selected abstracts of NTvG were determined. The authors made structured abstracts of all read articles of NTvG.\n Structured abstracts of AIM, BMJ and NEJM are clear and detailed. However information about key sociodemographic features of patients, their selection and the way of statistical analysis of the results was often missing. In NTvG articles essential information was lacking with respect to objective, design, setting of the study, sociodemographic features of patients, and patients and methods. Structured abstracts of articles in NTvG take more space: an average of 266 instead of 164 words.\n Structured abstracts take more space but are more informative. Authors of original articles in NTvG are advised to prepare structured abstracts. Editors and peer reviewers should ascertain that no essential information is lacking.", "To determine the accuracy of the bibliographic citations in theJournal of Anesthesia, all references appearing the years 1987 (Vol. 1;n=548) and 1994 (Vol. 8;n=1839) were sequentially numbered and 100 references from each year were randomly selected. After citations of non-journal articles were excluded (n=8 in 1987;n=7 in 1994), the remaining 185 citations were scrutinized. The authors' names, article title, journal title, volume number, page numbers, and year were examined for each reference. A reference was deemed correct if each clement of the citation was identical to its source. Of the references examined, 41% and 42% in 1987 and 1994, respectively, contained one or more errors. The elements that were inaccurate most often were, in descending order of frequency, article title, author, and page number. No significant differences existed in the error rate between the two years. We have demonstrated a considerable level of citation error in the reference lists of theJournal of Anesthesia articles, and no improvement over the last seven years. We recommend that contributors to theJournal of Anesthesia should carefully check the accuracy of their reference listings.", "Misspellings of transcription or the copy of references of articles published in the literature without verifying the information with the original document may be the cause of incorrect citations. The purpose of this study was to determine the accuracy of citations to journal articles in 1962 to 1992 volumes of Medicina Clínica.\n A method of systematic sampling was used to choose five references for each of the 12 original articles per year selected at 5-year intervals (1962, 1967, 1972, 1977, 1982, 1987, 1992). In the final sample of 420 references, errors in the six standard bibliographic elements--authors' names, article title, journal title, year, volume number, and page numbers--were analyzed. Major errors were defined when inaccuracies prevented identification of the cited article.\n Of the total 368 references verified, 132 (35.86%) were error free and the remaining 236 (64, 13%) were inaccurate. Multiple errors were found in 45% of cases. The mean number of errors per references was 1.13. Twelve references were incorrect, 221 errors were found in the authors' name, 131 in the title of the article, 14 in the name of the journal, 5 in the year of publication, 12 in the number of the volume, and 22 in the initial or final pages of the article. Major errors were detected in 94 (22.54%) cases and minor errors in 323 (77.45%). There were no statistically significant differences in the variation of the overall percentage of errors throughout the study period.\n A high rate of citation errors has been also documented in a Spanish medical journal. The importance of reference verification should be emphasized and authors should exercise more care in preparing bibliographies of their articles.", "The most-read section of a research article is the abstract, and therefore it is especially important that the abstract be accurate.\n To test the hypothesis that providing authors with specific instructions about abstract accuracy will result in improved accuracy.\n Randomized controlled trial of an educational intervention specifying 3 types of common defects in abstracts of articles that had been reviewed and were being returned to the authors with an invitation to revise.\n Proportion of abstracts containing 1 or more of the following defects: inconsistency in data between abstract and body of manuscript (text, tables, and figures), data or other information given in abstract but not in body, and/or conclusions not justified by information in the abstract.\n Of 250 manuscripts randomized, 13 were never revised and 34 were lost to follow-up, leaving a final comparison between 89 in the intervention group and 114 in the control group. Abstracts were defective in 25 (28%) and 30 (26%) cases, respectively (P=.78). Among 55 defective abstracts, 28 (51%) had inconsistencies, 16 (29%) contained data not present in the body, 8 (15%) had both types of defects, and 3 (5%) contained unjustified conclusions.\n Defects in abstracts, particularly inconsistencies between abstract and body and the presentation of data in abstract but not in body, occur frequently. Specific instructions to authors who are revising their manuscripts are ineffective in lowering this rate. Journals should include in their editing processes specific and detailed attention to abstracts.", "The purpose of this study was to quantify and classify errors in reference lists of randomly selected, recently published issues of nursing journals (n = 17) and to assess whether these errors prevented retrieval of the cited documents. Randomly selected references, 65 from clinical journals and 47 from non-clinical journals, were compared to the original sources for accuracy. Errors were classified as minor (not preventing retrieval) and major (preventing retrieval). Errors occurred more frequently in references in clinical journals, 38.4% of those reviewed, as compared to 21.3% in of non-clinical journals. Additionally, 4.6% of the clinical references contained major errors, but no major errors were located in references from the non-clinical journals. These findings have implications for all readers.", "nan", "nan", "The purpose of this study was to determine whether an example in a technical research report would affect application of content to hypothetical patient problems and to future patients.\n Subjects were 69 physical therapists who routinely used isokinetic equipment in the treatment of patients with knee joint pathologies.\n Thirty-five subjects (group 1) read a research report that described mathematical models for predicting preinjury quadriceps femoris and hamstring muscle performance. The report included an example of applying the information. The remaining 34 subjects (group 2) read the same research report with the example omitted. Subjects were asked to select appropriate prediction models and determine preinjury knee torques for two hypothetical patients. Subjects were also contacted 6 to 12 weeks after initial data collection to determine whether they had applied research report results in their treatments of patients.\n Chi-square analyses indicated manuscript type was not related to the selection of correct models, but group 1 subjects computed correct torque values more frequently than did group 2 subjects. Insufficient data were available regarding application of research report content to patients.\n The results indicate application of technically oriented research reports may be enhanced by including examples of applications. (Gross MT, Sekerak DK, Allen DD. Effect of including a clinical example on the ability of physical therapists to apply information in a technical research report.", "To determine the rate and type of errors in biomedical informatics journal article references.\n References in articles from the first 2004 issues of five biomedical informatics journals, Journal of the American Medical Informatics Association, Journal of Biomedical Informatics, International Journal of Medical Informatics, Methods of Information in Medicine, and Artificial Intelligence in Medicine were compared with MEDLINE for journal, authors, title, year, volume, and page number accuracy. If discrepancies were identified, the reference was compared with the original publication. Two reviewers independently evaluated each reference.\n The five journal issues contained 37 articles. Among the 656 eligible references, 225 (34.3%) included at least one error. Among the 225 references, 311 errors were identified. One or more errors were found in the bibliography of 31 (84%) of the 37 articles. The reference error rates by journal ranged from 22.1% to 40.7%. Most errors (39.0%) occurred in the author element, followed by the journal (31.2%), title (17.7%), page (7.4%), year (3.5%), and volume (1.3%) information.\n The study identified a considerable error rate in the references of five biomedical informatics journals. Authors are responsible for the accuracy of references and should more carefully check them, possibly using informatics-based assistance.", "The accuracy of references was assessed in Turkish journals of orthopedics and traumatology.\n All references cited in four journals (Acta Orthopaedica et Traumatologica Turcica, Arthroplasty Arthroscopic Surgery, Hacettepe Journal of Orthopaedic Surgery, and The Journal of Turkish Spinal Surgery) throughout 1995 to 1999 were numbered consecutively. One percent of references from each journal was randomly selected to be evaluated in comparison with primary sources. Errors were classified in three categories. Another randomized selection was made to check 50 references from each journal. The results were assessed by the t-test.\n Of 18,193 references cited in four journals, 182 references were checked. Errors were found in 117 references (63%), seven of which were major errors that prevented location of the primary source. When 50 references were checked from each journal, the mean inaccuracy rate was 60%. No significant differences were found between the journals with respect to the frequency of erroneous references.\n The high rate of inaccuracy emphasizes the need for greater care in the use of references on the part of authors, journal editors, and reviewers.", "nan", "The section of a research article most likely to be read is the abstract, and therefore it is particularly important that the abstract reflect the article faithfully.\n To assess abstracts accompanying research articles published in 6 medical journals with respect to whether data in the abstract could be verified in the article itself.\n Analysis of simple random samples of 44 articles and their accompanying abstracts published during 1 year(July 1, 1996-June 30, 1997) in each of 5 major general medical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, and New England Journal of Medicine) and a consecutive sample of 44 articles published during 15 months (July 1, 1996-August 15, 1997) in the CMAJ.\n Abstracts were considered deficient if they contained data that were either inconsistent with corresponding data in the article's body (including tables and figures) or not found in the body at all.\n The proportion of deficient abstracts varied widely (18%-68%) and to a statistically significant degree (P<.001) among the 6 journals studied.\n Data in the abstract that are inconsistent with or absent from the article's body are common, even in large-circulation general medical journals.", "We have reviewed the reference citations in volume 1 (1995) and volume 2 (1996) of the Hong Kong Medical Journal to determine their accuracy. One hundred references were randomly selected from each volume. After excluding references not from indexed journals, all citations were examined in detail by dividing them into six component elements and comparing them with the original. We found that 61% of references in volume 1 and 51% of references in volume 2 contained inaccuracies, giving an overall error rate of 56%. Thirty-eight percent of references contained errors in one element, 16% contained errors in two elements, and 2% contained errors in three or more elements. The most common errors were those of the title or authors' names. The rate of citation errors in the Hong Kong Medical Journal is at the high end of the range compared with other medical journals. Contributors to this journal need to take more care in checking their references before publication.", "A considerable number of quotational inaccuracies have been detected in medical and surgical publications in the past. Our study investigated the quotational accuracy of selected references of 32 scientific publications in six anesthesia journals referring to a single article published in a 1973 issue of the British Journal of Anaesthesia. In four (12.5%) articles, the quotation was in contradiction to the primary author's statement; in 15 (46.9%) articles, it was selective; and in 13 (40.6%) publications, it was in complete agreement with the important statements made in the original article. These results suggest that quotational inaccuracy is also evident in neuroanesthesiologic research. This problem deserves increased attention by authors as well as by reviewers and journal editors.", "The reference list is an important part of a scientific article. To be useful it must be accurate.\n The purpose of this study was to evaluate the accuracy of references in the dermatologic literature.\n We randomly selected 240 references (60 per journal) from the Archives of Dermatology, the British Journal of Dermatology, this Journal, and the Journal of Investigative Dermatology and checked them against the original articles.\n The overall rate of citation error (the information identifying the source) was 41%, and the quotation error (inconsistency between the statement referenced and the original source) was 35%. Only 36% of references were free of error.\n This study shows that the rate of citation and quotation errors is unacceptably high in the dermatologic literature, which significantly diminishes the value of the reference list.", "To determine the accuracy of bibliographic citations in three widely circulated nursing journals, RN, Nursing Management, and Image: Journal of Nursing Scholarship. Accurate citations facilitate retrieval of the cited documents and establish the judgment and credibility of authors.\n Descriptive, comparative.\n A random sample of 60 references per journal published July 1995 to June 1996 was reviewed for citation and quotation accuracy. Errors were classified as major or minor. Data were analyzed using the SAS statistical package.\n Of the 180 references, 58 (32%) had citation errors, with 43 of 58 errors classified as major errors, which made retrieval of the cited work difficult; 12 of the 180 articles contained a major quotation error, including four instances where the content of the original article contradicted or was unrelated to the author's contention.\n The rate of citation and quotation errors in the three sampled nursing journals is comparable to rates previously reported for medical and nursing journals. Errors of citation and quotation diminish the value of published papers.", "Previous studies have noted the prevalence of errors in journal reference lists, including nursing journals, but an in-depth study of nursing research journals has not been repeated.\n The purpose of this study was to determine the number and types of errors in nursing research journal reference lists.\n A stratified random sample of 262 references from three nursing research journals was obtained. References were compared with the actual articles, books, and chapters cited, or with photocopies obtained via interlibrary loan. Error rates were calculated.\n The overall error rate was 45.8%; 38.3% of all references contained at least one major error, and 13.8% of all references contained at least one minor error.\n The overall rate of reference errors falls within the range exhibited by recent studies of the medical and dental literature but exceeds the rates found in studies of nursing journals and veterinary medicine journals. Researchers need to consider the number and types of errors involved when using reference lists in their research.", "Several studies have evaluated the accuracy of bibliographic citations in the medical literature. The purpose of this study was to evaluate the accuracy of 300 reference citations in 10 dental journals. Thirty references were randomly selected from the January 1991 issue of 10 dental journals, for a total of 300 reference citations. Almost all of the citations were verified from the original source; a few were identified from other library sources. Only two references were unable to be identified, and they were both from foreign journals. This survey found 78% (n = 234) of the citations verified (n = 298) to be correct.", "Results from original studies are not always correctly represented in subsequent medical publications. In this study, randomly selected quotations from Israeli medical journals were examined. Less than 80% of the examined statements were in complete agreement with the original source. In about 7% the cited reference failed to substantiate the previous author's statement. Similar results were found over a range of American and European general and speciality journals. It is concluded that errors in quotation are a widespread problem in the biomedical literature. Editors and peer reviewers can improve quotation accuracy by stressing this issue in decisions regarding publication. Nevertheless, it seems that the most efficient solution would be for authors to increase their vigilance in accurately quoting results and statements from previous publications.", "Reference lists serve as a resource for the reader and provide support for the author's ideas. Errors in references reflect poorly on the author and journal and may prevent locating the referenced articles. The purpose of this study was to determine the number and types of errors in references in 3 critical care nursing journals: Journal of PeriAnesthesia Nursing, American Journal of Critical Care, and Critical Care Nurse. There were 2,444 citations in 13 issues of these journals during the study period. Ten percent of the references from each journal was selected randomly and analyzed for accuracy. Of the 244 references examined, 56 contained errors for an overall error rate of 22.9%. Major errors, such as misspelled or omitted author names and initials, occurred in 19.6% of the references. Minor errors, including non-first page discrepancies, occurred in 4.5% of the references. Errors in author names combined with incorrect or missing volume or issue numbers were the 2 most common errors, accounting for 61% of errors. The overall error rate for these 3 critical care nursing journals was lower than the rates reported for other nursing journals.\n Copyright 2002 by American Society of PeriAnesthesia Nurses.", "This study examined the readability of the AANA Journal, quantifying the effect of peer review on case and research reports published from 1992 to 1994. Gunning and Flesch index-based computer analysis, as well as human comparative analysis, was undertaken. Computer and human assessment of readability revealed improvement as papers evolved from submitted to published versions; however, at publication the manuscripts remained in the \"difficult\" readability range. Although this study provides evidence that peer review improves readability, it may be that, due to a professed need for scientific purity and an imposed sense of scholarship, nursing and other biomedical journals may overemphasize a style and approach that paradoxically make transfer of information unreasonably difficult.", "nan", "We verified a random sample of 50 references in the May 1986 issue of each of three public health journals. Thirty-one per cent of the 150 references had citation errors, one out of 10 being a major error (reference not locatable). Thirty per cent of the references differed from authors' use of them with half being a major error (cited paper not related to author's contention).", "A previous study indicated that there were many citation errors in the Canadian Journal of Anaesthesia. After this report, editors of the Journal requested any contributors, whose papers were accepted for publication, to verify the accuracy of reference citation by including a photocopy of the first page of each reference. The present study examined if the accuracy of the reference list had improved. We compared citation errors between volumes of 1990 and 1994. One hundred references from each year's publication were randomly selected. After citations of nonjournal articles were excluded, the remaining 190 citations were carefully scrutinized. Authors' names, article title, journal title, volume number, page numbers, and year were examined in each selected reference. A reference was deemed correct if each element of the citation was identical to its source. Of the examined references, 48% and 22% contained one or more errors in 1990 and 1994, respectively. Errors in the title and author field of citation were most common in the either of the two years, occurring in about 70% of the references which contained some errors. Citation errors in Canadian Journal of Anaesthesia were considerably improved after the request to verify citation accuracy. Although this check-system probably contributes to the improvement of accuracy of reference citation, the rate of citation errors remains high. We believe that contributors' efforts will enhance the value of the journal.", "The high rate of citation errors in bibliographies in medical journals has been a source of concern in recent years. We examined the accuracy of references published during 1 year in two Israeli medical journals. Only two-thirds of the randomly selected references examined were error free; 8% had major errors preventing identification of the cited article. Most of the errors found (76%) were in referencing the author(s) or title of the article. We conclude that errors in citation appear also in Israeli medical journals. Editors should emphasize the importance of reference verification; however, primary responsibility for the accuracy of the reference list rests with the author. Authors should exercise more care in preparing bibliographies and should invest more effort in verification of quoted references.", "To compare the recall and precision of citation retrieval from MEDLINE when searching in journals containing traditional abstracts with journals containing abstracts prepared according to the guidelines of more informative abstracts (MIAs) for clinical journal articles.\n Analytic survey of operating characteristics of MeSH terms and textwords selected to detect studies meeting basic methodological criteria for direct clinical use in general adult medicine in priority journals with and without MIAs.\n The sensitivity, specificity, and precision of search terms were determined by comparison with a manual review of all articles (the gold standard) in 10 internal and general medicine journals for 1986 and 1991. The performance of each search term was compared before and after the implementation of MIAs and in two journal sets with and without MIAs in 1991.\n The sensitivity of some terms increased with the use of MIAs and also increased by the same amount in journals with usual abstracts in 1991 compared to 1986. The use of MIAs had the greatest impact in the areas of etiology and prognosis. Many MeSH and textwords had comparable performance before and after the implementation of MIAs and between journals with and without MIAs in 1991.\n More informative abstracts improved the retrieval properties of some, but not all, textwords and medical subject headings. Further work may be needed to enhance the effects of MIAs on bibliographic retrieval.", "To characterize the structured abstracts in biomedical journals indexed in MEDLINE over a three-year period as an initial step in exploring their utility in enhancing bibliographic retrieval.\n The study examined the occurrence of structured abstracts in MEDLINE from March 1989 to December 1991, characteristics of MEDLINE records for articles with structured abstracts, editorial policies of six selected MEDLINE journals on structured abstracts, and a sample of twenty-five structured abstracts from the six journals.\n The study revealed that the number of structured abstracts in MEDLINE and the number of MEDLINE journals publishing structured abstracts increased substantially between 1989 and 1991. On average, articles with structured abstracts had more access points (Medical Subject Heading [MeSH] terms and text words) than MEDLINE articles as a whole. The average length of the structured abstract was greater than the average length of all abstracts in MEDLINE.\n The presence of structured abstracts may be associated with other article characteristics that lead to the assignment of a higher average number of MeSH headings or may itself contribute to the assignment of more headings. The variations in the structured-abstract formats prescribed by different journals may complicate the exploitation of these abstracts in bibliographic retrieval systems. More research is needed on a number of questions related to the quality and utility of structured abstracts.", "Errors in reference citation and use are common in the medical and scientific literature. The prevalence of such errors in the radiology literature has not been reported. We did a study to assess the accuracy and appropriateness of use of references cited in two general radiology journals.\n All references cited in the June 1993 issues of the American Journal of Roentgenology and Radiology were numbered consecutively. Fifty references were chosen at random from each journal, and copies of the original publications were obtained from the medical library at our institution or through interlibrary loan. Each reference was studied for accuracy and appropriateness of its citation in the June 1993 journal article (the \"index article\"). Errors were classified as major or minor in each category. Data were analyzed with the SAS statistical package.\n Forty-seven (94%) of 50 references were obtained from AJR, and 48 (96%) of 50 from Radiology. Of the 47 from the AJR, one (2%) had a major error and 21 (45%) had a minor error in accuracy. Of the 48 from Radiology, two (4%) had a major error and 11 (23%) had a minor error in accuracy. These values were significantly different for minor errors (p = .0188), but not for major ones (p = 1.000). When we adjusted for index article type, error rates for the two journals were not significantly different (p = .0612). We found four major errors (9%) and two minor errors (4%) in appropriateness of citation in the AJR references we studied. Three references (6%) from Radiology contained major errors in appropriateness of use; we found no minor errors of that type. These values were not significantly different (p = .232 for minor errors; p = .709 for major errors). One error in accuracy prevented location of the original reference. Errors were not related to the number of references cited in an index article (p = .528 for accuracy; p = .092 for appropriateness).\n The rate of minor errors in accuracy of references is fairly high in the two journals studied and is comparable to rates previously reported for other types of journals. The rate of major errors in accuracy of references is slightly lower than rates for other types of journals. The percentage of cited references that could not be located was also smaller than in previous reports. Errors in citation appropriateness were less common as well. Given the small number of errors that prevented references from being located, significant expenditure of time and money by journal staff members in checking references is probably not justified. However, authors should be encouraged to exercise greater care in checking all of their references for both accuracy and appropriateness of use. Differences in error rates between AJR and Radiology may have resulted in part from the random sampling method, which produced different mixtures of index articles for the two journals.", "To evaluate the accuracy of bibliographic references in REVISTA ESPANOLA DE ANESTESIOLOGIA Y REANIMACION (REDAR) and compare it with other Spanish and international journals.\n One hundred references were selected at random from those published in REDAR during 1994. A citation was considered correct if there were no differences between it and the original article in any of 6 standard citation times, and if it complied with REDAR citation style. A citation was considered incorrect if there were in fact differences or if REDAR style was not followed. Errors that interfered with direct access to the original were considered serious. Also considered serious were the omission of the first author.\n Some type of error was detected in 53.9% of the references. Twelve contained a serious error, which on 5 occasions impeded finding the original article and on 6 occasions made direct access difficult. The first author was missing in 1 citation. Errors were found, in order of decreasing frequency, in authors, article titles, journal title, volume, pages and year. A single error was found in 28 citations, 2 were found in 12, 3 were found in 2 and more than 3 were found in 1.\n REDAR's rate of error in references is comparable to the rates of other Spanish journal, but it is nearly double that of international journals in anesthesiology with higher impact factors (Anesthesiology, Canadian Journal of Anaesthesia). An effort must be made by authors and editors to remedy the situation.", "We analysed the reference error rate of four paediatric journals. The overall rate was 29.7%. Individual rates were as follows: Acta Paediatr 36%, Arch Dis Child 22%, J Pediatr 29%, Pediatrics 32%; the rate of major errors was 1%, 1%, 2%, and 4%, respectively.", "nan", "nan", "nan", "The accuracy of reference citations in The Australian and New Zealand Journal of Surgery was evaluated. All of the references from 1995 (Volume 65) were included (n = 4092).\n A sample of 100 references was randomly selected and examined in detail by comparison with the original references.\n Overall, 60% of citations contained errors. Errors were categorized by dividing references into six elements. A total of 38.8% of citations contained an error in one element, 15.6% contained errors in two elements, 4.4% contained errors in three elements, and 4.4% contained errors in four elements of the reference. The most common errors were errors of authors' names and errors in the title.\n Contributors to this journal should take more care in checking references in the manuscripts before publication.", "A high rate of errors of citation and quotation has been reported in the publications of many medical specialties. The aim of this study was to determine the prevalence of citation and quotation errors in otolaryngology/head and neck surgery journals. A retrospective analysis was performed based on the first issue for 1997 of each of four journals: Laryngoscope; Annals of Otology, Rhinology and Laryngology; Clinical Otolaryngyology; and Journal of Laryngology and Otology. A sample of 50 references from each journal was randomly selected and each was checked for accuracy against the original referenced paper. Citation errors were categorized as major, intermediate or minor and quotation errors as major or minor. Citation errors occurred in 37.5% of the references, 11.9% of which were considered major errors. Quotation errors occurred in 17%, with 11.1% major errors. This prevalence is similar to the established error rate in medical literature." ]

[ "2508467", "9859905" ]

[ "Nasal intermittent positive-pressure ventilation offers no advantages over nasal continuous positive airway pressure in apnea of prematurity.", "Efficacy of nasal intermittent positive pressure ventilation in treating apnea of prematurity." ]

[ "A prospective, randomized, cross-over trial was performed to compare the efficacy of nasal intermittent positive-pressure ventilation with nasal continuous positive airway pressure in infants of less than 32 weeks of gestation. Continuous positive airway pressure was delivered at end-expiratory pressures of 4 cm H2O, while peak pressures of 20 cm H2O and end-expiratory pressures of 4 cm H2O were used during nasal intermittent positive-pressure ventilation at ventilatory rates of 20 breaths per minute. The frequency and extent of apnea and bradycardia during a 6-hour period in a patient receiving nasal continuous positive airway pressure were compared with a similar crossover period of nasal intermittent positive-pressure ventilation. Although the infants had slightly less frequent episodes of apnea per hour (0.6 +/- 0.7 vs 0.5 +/- 0.7) and bradycardia per hour (1.2 +/- 1.3 vs 0.9 +/- 1.0) during nasal intermittent positive-pressure ventilation, these differences were not significant. There were no significant differences in the severity of these events as assessed by the duration and fall in transcutaneous oxygen pressure during apnea and heart rate during bradycardia. There were no significant changes in blood gases throughout the study. Nasal intermittent positive-pressure ventilation appears to have no advantages over nasal continuous positive airway pressure in preventing apnea and does not alter gas exchange in infants of less than 32 weeks of gestation.", "The efficacy of nasal intermittent positive pressure ventilation (NIPPV) in treating apnea of prematurity was evaluated. Apneic preterm infants were randomly assigned to receive either NIPPV or continuous positive airway pressure (NCPAP) for 4 hr when they failed to respond to conservative therapy. The amount of reduction in apneic spells and bradycardia in the two groups after treatment was compared. Thirty-four infants (18 with NIPPV, 16 with NCPAP) were enrolled. Their birth weights ranged from 590-1,880 g (mean, 1,021 g) and gestational ages from 25-32 weeks (mean, 27.6 weeks). The baseline characteristics were comparable in the two groups. Frequency of apnea and bradycardia was reduced during both forms of treatments. However, the infants receiving NIPPV had a greater reduction of apneic spells (P = 0.02) and a tendency to greater decrease in bradycardia (P = 0.09) than those receiving NCPAP. We conclude that NIPPV is more effective than NCPAP in reducing apnea in preterm infants. NIPPV may reduce bradycardia; however, this needs to be validated by a larger number of observations." ]

[ "14674933", "7735519", "11834182", "17114889", "17321581", "15562880", "15507097", "16792583", "12811019", "9684190", "18211754", "18585908", "8526180", "9700035", "18088023", "19764942", "9260215", "17935764", "10550740", "9500318", "11674922", "17064648", "16630937", "18051216", "7551201", "10452766", "19046761", "15080830", "11450599", "12680861", "16942565", "16409194", "16890769", "14635462", "10485385", "15480323", "10505460" ]

[ "Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study.", "Double-blind, placebo-controlled clinical trial of preseasonal treatment with allergenic extracts of Olea europaea pollen administered sublingually.", "Efficacy of sublingual specific immunotherapy in Cupressaceae allergy using an extract of Cupressus arizonica. A double blind study.", "Safety and efficacy of Juniperus ashei sublingual-swallow ultra-rush pollen immunotherapy in cypress rhinoconjunctivitis. A double-blind, placebo-controlled study.", "Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care.", "Canadian trial of sublingual swallow immunotherapy for ragweed rhinoconjunctivitis.", "A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen.", "Randomized double-blind controlled study with sublingual carbamylated allergoid immunotherapy in mild rhinitis due to mites.", "A double-blind placebo-controlled evaluation of sublingual immunotherapy with a standardized ragweed extract in patients with seasonal rhinitis. Evidence for a dose-response relationship.", "Immunotherapy with sublingual birch pollen extract. A short-term double-blind placebo study.", "[Clinical evaluation for sublingual immunotherapy of allergic asthma and atopic rhinitis with Dermatophagoides Farinae Drops].", "Double-blind, placebo-controlled evaluation of grass pollen specific immunotherapy with oral drops administered sublingually or supralingually.", "Safety and efficacy of sublingual rush immunotherapy with grass allergen extracts. A double blind study.", "Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization.", "Efficacy and quality of life with once-daily sublingual immunotherapy with grasses plus olive pollen extract without updosing.", "Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study.", "Double-blind placebo-controlled study of sublingual immunotherapy with house dust mite extract (D.pt.) in children.", "Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis.", "Clinical and immunologic effects of a rush sublingual immunotherapy to Parietaria species: A double-blind, placebo-controlled trial.", "Randomised controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis.", "Sublingual immunotherapy in tree pollen allergy. Double-blind, placebo-controlled study with a biologically standardised extract of three pollens (alder, birch and hazel) administered by a rush schedule.", "Clinical efficacy and safety of preseasonal sublingual immunotherapy with grass pollen carbamylated allergoid in rhinitic patients. A double-blind, placebo-controlled study.", "Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis.", "Sublingual-swallow immunotherapy with standardized 3-grass pollen extract: a double-blind, placebo-controlled study.", "Sublingual immunotherapy in Parietaria pollen-induced rhinitis: a double-blind study.", "Double-blind placebo-controlled evaluation of sublingual-swallow immunotherapy with standardized Parietaria judaica extract in children with allergic rhinoconjunctivitis.", "Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis.", "Efficacy of sublingual swallow immunotherapy in children with severe grass pollen allergic symptoms: a double-blind placebo-controlled study.", "[Sublingual immunotherapy with cat epithelial extract. Personal experience].", "House-dust mite sublingual-swallow immunotherapy in perennial conjunctivitis: a double-blind, placebo-controlled study.", "Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract in children.", "Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis.", "Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis.", "Double-blind, placebo-controlled study with sublingual immunotherapy in children with seasonal allergic rhinitis to grass pollen.", "Sublingual-swallow immunotherapy (SLIT) with a standardized five-grass-pollen extract (drops and sublingual tablets) versus placebo in seasonal rhinitis.", "Randomized controlled trial of high-dose sublingual immunotherapy to treat seasonal allergic rhinitis.", "Sublingual immunotherapy: a double-blind, placebo-controlled trial with Parietaria judaica extract standardized in mass units in patients with rhinoconjunctivitis, asthma, or both." ]

[ "Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed.\n To investigate the clinical efficacy of SLIT vs SCIT and secondary to compare SLIT and SCIT with placebo and to evaluate the relative clinical efficacy in relation to systemic side-effects.\n A 3-year randomized, placebo-controlled, double-blind, double-dummy study including 71 adult birch pollen hay fever patients treated for two consecutive years after a baseline year. Allocation to treatment groups was based on disease severity in the baseline season, gender and age.\n Clinical efficacy was estimated in 58 patients completing the first treatment year by subtracting baseline data and by calculating the ratio first treatment season vs baseline. SLIT diminished the median disease severity to one-half and SCIT to one-third of placebo treatment. No statistical significant difference between the two groups was observed. Both for symptoms and medication scores actively treated patients showed statistically significant and clinical relevant efficacy compared with placebo. SLIT treatment only resulted in local mild side-effects, while SCIT resulted in few serious systemic side-effects.\n Based on the limited number of patients the clinical efficacy of SLIT was not statistically different from SCIT, and both treatments are clinically effective compared with placebo in the treatment of birch pollen rhinoconjunctivitis. The lack of significant difference between the two treatments does not indicate equivalent efficacy, but to detect minor differences necessitates investigation of larger groups. Due to the advantageous safety profile SLIT may be favored.", "In a double-blind, placebo-controlled, pilot clinical trial we evaluated the clinical efficacy and safety of immunotherapy (IT) with an extract of the pollen of the tree Olea europaea administered sublingually. The parameters tested were symptom score, dose-response bioassay of skin prick test and specific IgE and IgG, and the absolute value at a single serum dilution of each IgG subclass. Fifteen patients allergic to this pollen with symptomatology of rhinitis and/or rhinoconjunctivitis were randomly allocated to the placebo group (6 patients) or to the extract group (9 patients). Immunotherapy was administered in a short preseasonal period of time, practically no side effects being recorded. The group of patients treated with extract presented a slightly lower incidence (0.05 < p < 0.1) of nasal symptoms of sneezing and obstruction, and, more importantly, developed less dyspnea (p < 0.05) than the group treated with placebo, suggesting that IT can act as prophylaxis for the development of bronchial symptoms. No differences were observed in the immunological determinations. Differences in skin tests between the two groups displayed a slight significance (0.05 < p < 0.1) at the end of the trial; hence, a higher concentration of the allergen was needed in the group treated with extract to induce the same wheal as in the placebo group. In both groups the size of the wheal showed a time-dependent variation, which was dependent on the time of the year and independent of the type of treatment received, indicating a significant modification in the in vivo skin response to allergen challenge, demonstrated by a shift in the kinetics of allergen-ligand binding (slope) and in the magnitude of the measured response (intercept).", "non-injective routes of immunotherapy in respiratory allergy have being proposed as an alternative to conventional immunotherapy. We carried out a study to evaluate the clinical efficacy and effects sublingual immunotherapy (SLIT) in patient with Cupressaceae pollen respiratory allergy.\n twenty patients with Cupressaceae pollen (C. sempervirens) rhinoconjunctivitis, mild asthma or both were randomly chosen for sublingual immunotherapy (10 patients) or placebo treatment (10 patients) using a double blind placebo controlled technique. We have used an extract of Cupressus arizonica because of its better stability in solution and its crossreactivity with Cupressus sempervirens. The patients underwent treatment for 12 months (from april 1999 to april 2000). Symptoms and drug scores as well as nasal provocation tests were recorded. The pollen counts were carried out, during all the same period.\n we found significantly lower symptom scores (p < 0.05) and drug consumption scores (p < 0.05) in the immunotherapy group than in the placebo group, during the pollen season, after the first year of therapy. Besides threshold of allergen reactivity in nasal provocation tests was increased in the active group (p < 0.01). No untoward reactions have been observed.\n SLIT with Cupressus arizonica (pollen extracts) produced, after one year treatment, a significant improvement of allergic symptoms and a decrease of drug consumption scores and allergen-specific nasal reactivity. SLIT with Cupressus arizonica appeared to be effective and safe in the treatment of Cupressaceae pollen respiratory allergy.", "The safety and efficacy of high-dose sublingual-swallow immunotherapy (SLIT) has been established in pollen rhinoconjunctivitis. This treatment has now been evaluated using an ultra-rush incremental dose regimen with a Juniperus ashei allergen extract in patients allergic to Cupressus sempervirens and Cupressus arizonica.\n Patients received either placebo or SLIT. Evaluation of safety was based on the frequency of adverse events during the incremental dose period (half a day) and during maintenance therapy (4 months). Evaluation of efficacy was based on symptom and medication scores at the pollen peak.\n Seventy of the 76 patients included completed the study. There were no drop-outs during the rush procedure. One patient in the active group dropped out during the maintenance therapy due to adverse events: gastric pain and vomiting. There was also 1 drop-out in the placebo group due to pregnancy. Adverse events were infrequent, local and mild. Symptom scores for rhinitis and conjunctivitis were not statistically different between groups, but there was a marked and significant (p < 0.03) decrease of the medication score (about 50%) and nasal steroid consumption (about 75%) in the active treatment group. An increase from baseline of serum IgE and IgG4 J. ashei-specific antibodies was only observed in actively treated patients (p < 0.04 and p < 0.01, respectively).\n The tolerability and safety of high-dose ultra-rush SLIT were comparable to those reported in previous SLIT studies. SLIT with J. ashei extract, due to its high Jun a 1 content, significantly reduced nasal steroid consumption in patients allergic to European cypress.", "Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in referral centers.\n To investigate the efficacy of SLIT with grass pollen allergen in children and adolescents with rhinoconjunctivitis in a primary care setting.\n Youngsters aged 6-18 years with hay fever were enrolled from general practices and randomly assigned to receive placebo or grass pollen mix for 2 years. The primary outcome was the mean daily total symptom score (scale 0-15) comprising sneezing, itching nose, watery running nose, nasal blockage, and itching eyes during the months May-August of the second treatment year.\n Out of 204 youngsters randomized, 168 entered the intention-to-treat analysis (91 verum, 77 placebo). The mean daily total symptom score did not differ between participants allocated to verum and those allocated to placebo (difference for verum minus placebo: -0.08, 95%CI, -0.66-0.50; P = .78). No differences were found for rescue medication-free days, disease-specific quality of life, and overall evaluation of the treatment effect. Local side effects were more frequent in the verum group (39% vs 17% of participants; P = .001).\n Sublingual immunotherapy with grass pollen in a primary care setting is not effective in children and adolescents.\n Currently, SLIT cannot be recommended for general practitioners as a therapeutic modality in youngsters with grass pollen allergy.", "Sublingual swallow immunotherapy has been increasingly recognized as a safe and efficacious alternative to parenteral specific immunotherapy.\n To determine the safety and efficacy of sublingual swallow immunotherapy ragweed allergen extract for rhinoconjunctivitis treatment starting just before and continuing through the ragweed pollen season.\n This randomized, double-blind, placebo-controlled study was performed in children and adults with a documented history of allergic rhinoconjunctivitis during ragweed season at 9 Canadian allergy centers. Active treatment was standardized extract of ragweed allergen administered as sublingual swallow drops at increasing doses starting shortly before the pollen season and maintenance doses continued daily during the season. Primary efficacy variables were symptom and medication scores, and secondary variables included global evaluation of efficacy and immunologic measurements.\n Eighty-three patients were included in the safety analysis; 76 patients were included in the intent-to-treat analysis. Nine placebo recipients and 1 treatment recipient withdrew for lack of efficacy (P = .004). Nine patients in the treatment group withdrew because of adverse events, none serious (P = .003). Investigator evaluation of efficacy showed that significantly more patients improved and fewer deteriorated in the treatment group vs the placebo group (P = .047). Ragweed IgE and IgG4 levels increased significantly in treatment recipients vs placebo users (P < .001). Sneezing and nasal pruritus approached significant improvement in the treatment group vs the placebo group (P = .09 and .06, respectively). Quebec City experienced low pollen counts. Excluding Quebec City, significant improvement was seen for these 2 symptoms (P = .04).\n Sublingual swallow immunotherapy seems to be safe and efficacious for ragweed rhinoconjunctivitis even when started immediately before the ragweed pollen season.", "Especially in childhood, sublingual immunotherapy (SLIT) could offer advantages over subcutaneous therapy. However, limited data on its efficacy is available.\n In four German centres 97 children (age 3-14 years) with allergic rhinoconjunctivitis to grass pollen were enrolled in a prospective, double-blind trial comparing SLIT (Pangramin SLIT; ALK-SCHERAX, 0.5 microg major allergens, three times per week, 32 months) with placebo. Primary endpoint was a multiple symptom-medication score for changes in seasonal diary entries between the first and third year of the study (SLIT n=39; placebo n=38).\n The multiple symptom-medication score was significantly reduced by SLIT to 77.3% of the placebo group (P=0.0498). The subsequent analysis of the single endpoints did not reveal significant differences for symptom scores in favour of SLIT (85.1% of placebo group; P=0.22). However, the medication score improved significantly (67.1% of placebo group; P=0.0025). Furthermore, secondary endpoints assessing in vivo immune responses did not differ significantly between the groups. However, retrospective analysis showed some inhomogeneity for clinical and in vitro parameters at the beginning of the study. Allergic side effects with possible relation to the study drug were reported in both groups (SLIT 49%, placebo 27%, P=0.026).\n Our study indicates that SLIT had a positive effect on the reduction of a multiple symptom-medication score, mainly by significantly reducing rescue medication use, but had no significant effect on symptoms alone in children with rhinoconjunctivitis to grass pollen compared with a placebo.", "The clinical efficacy of sublingual immunotherapy (SLIT) in mite allergy and in mild disease is still a matter of debate, thus we performed a long-term clinical trial.\n The study was randomized, double-blind and placebo-controlled. After a 1-year assessment, 68 patients with mild rhinitis with/without asthma due to mites were randomized to drugs + placebo or drugs + SLIT for 2 years. Sublingual immunotherapy was given as soluble tablets of monomeric carbamylated allergoid. Clinical scores for asthma and rhinitis (0, absent to 3, severe) and drug consumption were assessed by diary card in the period November-February. Quality of life was assessed before and after each observation period and pharmaco-economy data were evaluated as well.\n Fifty-six patients completed the study. The rate of dropouts was similar in the two groups. No relevant side effect was reported. There was a significant reduction of total clinical scores (P < 0.05) in the active group vs placebo at the first year, but not at the second whereas nasal obstruction significantly improved in both years (P < 0.05). The reduction of drug intake score was significant only at the first year. No change was observed concerning most of the Short Form-36 items, because at baseline all patients displayed a normal profile. A significant change in SLIT group was seen for the item 'change in health status'. The need for extra visits was significantly lower in the active group (25%vs 43%).\n Sublingual immunotherapy was clinically effective and safe in mite-induced mild disease.", "There is a growing consensus on the benefits of sublingual-swallow immunotherapy in the treatment of allergic diseases.\n This randomized, double-blind placebo-controlled study was undertaken to assess the efficacy and safety of sublingual immunotherapy with standardized ragweed pollen extract tablets, in patients with an allergic rhinitis. A total of 110 outpatients were randomized (immunotherapy [I]: 55; placebo [P]: 55), of whom 99 were analyzable for efficacy (I: 48; P: 51) and 106 analyzable for safety (I: 53; P: 53). After a 28-day progression phase, the patients received a maintenance treatment during 6.5 months. Efficacy variables included a global assessment of efficacy (patient/ investigator), symptoms and medication scores as well as the frequency of asthma attacks.\n In the active treatment group, 43 patients completed the study, versus 49 on placebo. During the whole period of pollination, the difference favoring immunotherapy was highly significant for the global assessment by the patient (p = 0.004) and by the investigator (p = 0.005). Adverse reactions were reported more often in the active treatment but mild or moderate, and they abated after dose adjustment. A subgroup analysis of those patients receiving the highest dose of immunotherapy (3 tablets 3 times a week) showed a highly significant response for rhinitis and conjunctivitis total scores by comparison to lower dosages.\n This study confirms the efficacy and safety of sublingual immunotherapy and strongly suggests a dose-response relationship.\n Copyright 2003 S. Karger AG, Basel", "The aim of this double-blind placebo-controlled study was to evaluate the efficacy and tolerability of short-term birch pollen sublingual immunotherapy. Forty-one patients suffering from allergic rhinoconjunctivitis caused by Betula alba were included. Exclusion criteria were the following: undergoing immunotherapy within the last 2 years, contraindications to immunotherapy, pregnancy and nursing. The treatment schedule comprised a 28-day basic course, followed by a 3-month maintenance treatment. The evaluation of the parameters was performed before treatment and 4 months after the last maintenance dose. Skin prick test and conjunctival provocation test (CPT) in a dilution series were carried out to determine the threshold of the reaction. The objective parameters used were the diameter of the skin wheals and the lowest concentration, of the allergen extract to induce the symptoms of itching and reddening of the eyes. The allergic reaction in general was evaluated with the help of a 2-h birch pollen challenge in the Vienna Challenge Chamber (VCC); nasal flow and resistance was measured by rhinomanometry; and nasal secretion was quantified by weighing used handkerchiefs. Bronchial reactions were objectified by spirometry; subjective symptoms of the eyes, the nose and the bronchial tract were documented by the patients via a visual analog scale. Birch pollen specific IgE and IgG were evaluated by monoclonal antibody enzyme immunoassay before (T0) and after (T1) treatment. For statistics p < 0.05 was applied. At T0 there was no decisive difference in the in vitro and in vivo results between the two groups. After the treatment period (T1), actively treated patients showed a significantly higher tolerance to the birch pollen CPT (p < 0.01). The skin reaction was significantly lower than in the placebo group. Furthermore, actively treated patients produced less than half of the nasal secretion of placebo-treated patients during the challenge session. The rhinomanometry analysis during the challenge showed significant differences for verum and placebo in favor of the actively treated patients (p = 0.033). There was no significant difference in the specific IgE and IgG concentrations. The side effects and compliance during the treatment were comparable in both groups. In conclusion, sublingual immunotherapy is a well tolerated and clinically effective method of treatment.", "To evaluate the safety and efficacy of sublingual immunotherapy with 'Dermatophagoides Farinae Drops' in D. farinae allergic asthma and/or rhinitis patients.\n A 25-week double-blind, placebo-controlled, multi-centered trail was conducted in 278 children (aged 4 - 18 yr) with mite-induced asthma and/or rhinitis. Patients were randomly assigned to receive sublingual immunotherapy (SLIT) with 'Dermatophagoides Farinae Drops' (n = 139) or placebo (n = 139) for 25 weeks and the dosage and administration strictly followed the manufacturer's instructions. At the beginning of the 2nd, 3rd, 4th, 6th, 10th, 14th, 18th, 22nd week of the treatment, the patients were asked to accept follow-up visit, during the clinical trial all patients and parents were asked to keep a daily record of their asthma symptom scores, rescue medicine use, rhinitis symptom scores, morning and evening peak expiratory flow. Asthma symptom scores, reduction in use of rescue medicine, rhinitis symptom scores, lung function tests, skin sensitivity to mite, mite-specific immunoglobulin (Ig) E and IgG4, and quality of life and adverse effect were assessed during the study.\n (1) Of the 278 children, 27 dropped out before the study completion. (2) After 25 weeks of treatment, the median variability of PEFR was -1.38 for SLIT group and -0.90 for the placebo (P < 0.05). (3) Besides, the mean variability of medicine score of asthma was -0.08 for SLIT group and 0.52 for the plcebo (P < 0.05). (4) The median variability of rhinitis symptom score was -1.96 for SLIT group and -1.03 for the placebo (P < 0.01). (5) The rescue medicine usage of SLIT reduced but did not show significant differences between SLIT and placebo. (6) After 25 weeks treatment, the increase of D. farinae specific IgE antibody of two groups were similar, while specific IgG4 increased significantly in SLIT compared to the patients in control one (P < 0.01); (7) No severe adverse events happened in the trial and the most-likely adverse events were mild asthma and local rash.\n Dermatophagoides Farinae Drops is safe and effective in treating allergic asthma and atopic rhinitis.", "Forty-one patients suffering from grass pollen allergy underwent specific immunotherapy with standardized allergen extract consisting of six grass pollens (H-Al per os) administered either sublingually or supralingually for one year. In order to investigate clinical and immunological changes induced by the administration of allergens via the oral mucosa, the double-blind, placebo-controlled, randomized design of the trial with 30 other patients enrolled in placebo groups was applied. Specific immunotherapy with oral drops administered sublingually or supralingually was performed in the same way, keeping the drops under or on the tongue, respectively, for 1-2 min before swallowing them; at the end of the trial the cumulative dose of the allergen was almost 20 times higher than that of the subcutaneous therapy with corresponding allergen preparation. Data about symptoms scores and drugs intake during grass pollen season, as well as skin reactivity, levels of specific IgG and IgE antibodies, before the study and after the study's completion, were obtained. It was found that both routes of administration are effective according to subjective clinical parameters and drug consumption, with a highly significant reduction of symptoms and drug intake favoring sublingual administration where a reduction of more than 60% was achieved. Only sublingual active group showed a significant increase in Dactylis glomerata-specific IgG serum levels. Adverse effects were limited to a small number of generally mild local and/or systemic reactions. The results suggest that the administration of allergens via the oral mucosa is safe and clinically effective, favoring the sublingual rather than supralingual route.", "Thirty-four patients suffering from rhinoconjunctivitis with or without asthma due to grass pollen, were submitted to sublingual immunotherapy according to a double blind placebo controlled experimental plan; eighteen patients received the active therapy, sixteen the placebo. A rush preseasonal treatment schedule was followed in order to reach the maintenance dose in 15 days with two administrations per day; the top dose reached was then administered three times a week until the end of the pollen season. The symptoms and drugs related to rhinoconjunctivitis and asthma were recorded by means of diary cards and grass pollen counts were performed during the season. The actively treated group showed a reduction of symptoms of rhinoconjunctivitis and asthma and a lower intake of drugs for the same symptoms; all these differences resulted to be statistically significant. No patient showed local or systemic side effects of any relevance. According to these results of our study, sublingual rush immunotherapy is clinically effective and because of the ease of handling, the shortness of the treatment, the absence of relevant side effects and the high compliance of the patient can be considered as an alternative to classic injective immunotherapy in grass pollen allergic patients.", "For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose, 66 children with seasonal asthma, rhinitis, and conjunctivitis due to sensitization to olive pollen were enrolled in a double-blind, randomized, placebo-controlled study between October 1994 and October 1996 in Greece. Thirty-four patients were randomly allocated to the active group, and 32 received placebo. Immunotherapy consisted of olive-allergen extracts (Stallergènes SA) administered sublingually pre- and coseasonally from January to July for 2 consecutive years. Serial concentrations from 1 to 300 IR. were used up to the maintenance dose of 20 drops of 300 IR daily. The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy, and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years. The patients were assessed by clinical parameters (symptom and medication scores from patients' daily diaries) and immunologic measurements (specific IgE, IgG4, eosinophil cationic protein [ECP]) were performed. The actively treated patients had a significantly lower score for dyspnea (P<0.04 during the first season; P<0.03 during the second season). At the pollinic peak during the second year, a lower score of conjunctivitis was recorded (P<0.05) in the actively treated patients. The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo, whereas there was no symptomatic peak for the same period in the group under active treatment. However, the difference between the groups was not significant. The medication score did not differ significantly between the groups. Oral steroids were the only variables with a P value near the significance level (P=0.06) in favor of the actively treated group. A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment. No significant variation in specific IgE and IgG4 was detected. A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season (P=0.01), but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings. Tolerance was excellent with only a few minor side-effects reported. In conclusion, high-dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive-pollen sensitization.", "The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerance of once-daily sublingual immunotherapy without updosing. Reduction in symptoms and medication use was the primary endpoint.\n One hundred five patients with rhinitis and/or asthma due to grass and olive sensitization were randomized to be treated with placebo or active sublingual immunotherapy with the SLITone grass mix plus olive pollen extract for 6 months before the 2005 pollen season. Patients recorded symptoms and medication intake for 8 weeks during the pollen seasons in 2004 (n=37) and 2005 (n=85).\n Allergic symptoms were significantly decreased in the active immunotherapy group (P = .004) but not in the placebo group. There were no differences in scores between groups during the 2005 pollen season. Subjective assessments on a visual analog scale and a quality-of-life questionnaire indicated an improvement in actively treated patients with significant differences in both symptoms and medication use (P = .006). The rate of systemic adverse reactions was comparable in the 2 groups. No anaphylactic or severe adverse reactions were reported. Local adverse reactions, which were more common in the active immunotherapy group, were mostly immediate, were limited to the lips and mouth, and did not require treatment.\n Once-daily sublingual immunotherapy without updosing was well tolerated. The actively treated patients showed a significant reduction in symptom and medication scores and an improvement in their quality of life although there were no significant differences between the groups probably due to the low allergen season in which the study was evaluated.", "Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment.\n Patients (7.9-64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG(4) measured.\n Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8-92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between -11.3% and -14.8% for placebo (P < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and -1.51% for placebo (P < 0.05). Combined score (P = 0.0508) and symptom score improvements (P = 0.0144) with SLIT continued during follow up. Increases in specific IgG(4) observed in the first season were sustained for SLIT vs placebo throughout treatment (P = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported.\n Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT.", "Safety and efficacy of sublingual (sublingual-swallow) immunotherapy (IT) with house dust mite extract were evaluated in 30 children (6-15 2/3 years of age) over the first 12 months of an ongoing study. The cumulative dose was 570 micrograms Der p I (five times that administered with subcutaneous therapy). Safety: One patient on active treatment dropped out after 8 weeks because of a subjective feeling of severe weakness, questionably induced by the therapy. Five patients on active therapy and one patient on placebo reported minor local side effects. Efficacy: Pulmonary symptoms were reduced after 12 months in actively treated asthmatics, but this was not consistent with the lack of improvement in bronchial reactivity, skin sensitivity and specific IgG and IgG4 against D.pt. in this group. In patients with rhinitis nasal sensitivity was reduced in the placebo group without concomitant improvement in the nasal symptom score. Specific IgE (D.pt. and D.f.) increased significantly more in the active treatment group after 3 and 12 months. We conclude that sublingual IT over 12 months with the fivefold Der p 1 dose of subcutaneous IT was well tolerated, but there was no consistent clinical or immunological benefit compared to placebo.", "Sublingual immunotherapy is well tolerated and data suggest its effectiveness for the treatment of allergic rhinitis in adults, but it lacks optimum dose definition.\n To assess the efficacy, safety, and optimal dose of grass pollen tablets for immunotherapy of patients with allergic rhinoconjunctivitis.\n In this multinational, randomized, double-blind, placebo-controlled study, 628 adults with grass pollen rhinoconjunctivitis (confirmed by positive skin prick test and serum-specific IgE) received 1 of 3 doses of a standardized 5-grass pollen extract, or placebo, administered sublingually using a once-daily tablet formulation. The treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was Rhinoconjunctivitis Total Symptom Score; secondary outcomes included 6 individual symptom scores, rescue medication use, quality of life, and safety assessments.\n Both the 300-index of reactivity (IR) and 500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score (3.58 +/- 3.0, P = .0001; and 3.74 +/- 3.1, P = .0006, respectively) compared with placebo (4.93 +/- 3.2) in the intent-to-treat and per-protocol analyses. The 100-IR group (4.70 +/- 3.1) score was not significantly different from placebo. Analysis of all secondary efficacy variables (sneezing, runny nose, itchy nose, nasal congestion, watery eyes, itchy eyes, rescue medication usage, and quality of life) confirmed the efficacy of the 300-IR and 500-IR doses. No serious side effects were reported.\n In the first pollen season, the efficacy and safety of sublingual immunotherapy with grass tablets was confirmed. The 300-IR and 500-IR doses both demonstrated significant efficacy compared with placebo.\n The risk-benefit ratio favors the use of 300-IR tablets for clinical practice.", "The local (noninjection) routes of immunotherapy are presently regarded as viable therapeutic options for respiratory allergy, and their mechanisms of action are currently undergoing investigation.\n We evaluated the clinical efficacy of a preseasonal rush sublingual-swallow immunotherapy and its effects on allergic inflammation in patients with seasonal rhinoconjunctivitis caused by Parietaria species.\n Thirty patients with Parietaria species-induced rhinoconjunctivitis (13 with mild intermittent asthma) were randomly assigned sublingual-swallow immunotherapy or placebo in a rush preseasonal course. We assessed the seasonal symptom-drug intake score by diary card and the inflammatory infiltration and the intercellular adhesion molecule 1 expression on nasal epithelium after specific allergenic challenge before and after treatment.\n The investigated immunotherapy was well tolerated, and no side effects were recorded. A significant reduction of the symptom score (P =.016) and drug intake score (P =. 008) after immunotherapy was observed only in the active group. A decrease of the cumulative score was observed also in the placebo group (P =.046), but the significance was clearly higher (P =.006) in the active group. In the active group a reduction of neutrophils (P =.001), eosinophils (P =.01), and intercellular adhesion molecule 1 expression (P =.04) after specific nasal challenge was also detected.\n The present results suggest that this sublingual-swallow immunotherapy administered through a rush schedule is clinically effective and safe and that it decreases the immune-mediated inflammatory responses to the allergen.", "Non-injective routes of immunotherapy are thought to be valuable therapeutic options for respiratory allergy. We investigated the clinical efficacy and the effects of sublingual/oral immunotherapy on conjunctival allergic inflammation in patients with mite-induced respiratory allergy.\n We used a double-blind placebo-controlled design. 20 patients with mite-induced rhinoconjunctivitis (six of whom also had mild asthma) were randomly assigned sublingual/oral immunotherapy (n=10) or placebo (n=10) for 2 years. We assessed symptom score by diary cards and inflammatory-cell infiltrate, and expression of intercellular adhesion molecule 1 (ICAM-1) in the conjunctiva after specific allergen challenge at enrollment and after 12 and 24 months of treatment.\n We found significantly lower symptom scores in the immunotherapy group than in the placebo group in most of the winter months (p=0.05). Compared with the placebo group, inflammatory-cell infiltration after conjunctival challenge, and ICAM-1 expression on conjunctival epithelium decreased significantly in the first year of treatment in the immunotherapy group (p=0.04 and p=0.02, respectively). These effects were also seen for the minimum persistent inflammation, in symptom-free patients exposed constantly to allergens (p=0.02). Serum concentrations of eosinophil cationic protein decreased significantly (p=0.04). Immunotherapy was well tolerated and compliance was good.\n Our results suggest that this immunotherapy is clinically effective in rhinoconjunctivitis and that it decreases the immune-mediated inflammatory responses to the allergen.", "sublingual immunotherapy has been recognised as safe and effective but it is still poorly documented in tree pollen allergy. Allergy to alder, birch and hazel is important in Northern European countries but its clinical relevance is increasing in Southern Europe.\n thirty patients, selected and observed for one pollen season, were randomised to receive placebo (15 patients) or active treatment (15 patients). Twenty-seven patients completed the first year and 24 of them were treated with active therapy during the second year of the study in comparison to a parallel group of ten patients treated only with drugs. Symptom and drug scores during each pollen season, birch-specific IgE, changes in skin test reactivity, changes in specific Nasal Provocation Test and the daily average pollen count for the relevant trees were considered for the assessment of the efficacy of the treatment.\n both active and placebo group showed a statistically significant improvement in scores in comparison to the previous year, under a lower allergenic pressure. The improvement was higher in the active group (76.04 % reduction of drugs) but not significantly different from that registered in the placebo group (37.05 % reduction). In the open phase of the study, treated patients showed significantly better scores in comparison to the control group. No significant changes in skin reactivity, specific IgE and Nasal Provocation Test were registered. SLIT tolerance was very good.\n our data show a better but not statistically significant clinical outcome for patients actively treated with SLIT, but the placebo effect and the year-by-year variability of the environmental allergenic load in our small-size pilot study do not allow for a conclusive statement about the efficacy of this form of therapy.", "The aim of this study was to confirm the clinical efficacy and safety of a preseasonal sublingual immunotherapy (SLIT) in a group of allergic patients with seasonal rhinoconjunctivitis with or without mild intermittent or mild persistent asthma. The immunotherapy was administered through the oral mucosa with a monomeric carbamylated allergoid (allergoid SLIT) for grass pollens. A secondary endpoint was to evaluate the effect of the allergoid SLIT on nasal reactivity.\n A single-center, randomized, double-blind, placebo-controlled study was performed. Patients were selected and randomly allocated to two groups: one group received active treatment (allergoid SLIT) for 2 years and the other received placebo. Both groups received the necessary drug treatment throughout the trial. Thirty-three outpatients (20 men and 13 women, mean age: 30 years; range: 19-43) attending our center were enrolled in the study. Symptoms and medications were scored on diary cards during the pollen season. An allergen nasal challenge was performed at baseline and after 2 years of SLIT to evaluate nasal reactivity. Because the clinical scores were non-normally distributed, the Mann-Whitney and the Chi-square tests for intergroup comparisons and the Wilcoxon test for intragroup comparisons were used. The results were evaluated after 1 and 2 years of treatment. Between the first and second years of treatment, no changes in the scores for the placebo group were found, while for the active vaccine group significant decreases were found in rhinorrhea (p < 0.03), sneezing (p < 0.03), and conjunctivitis (p < 0.02). Symptom scores after nasal challenge decreased (p < 0.03) after 2 years' treatment. Nasal steroid use significantly decreased in the active treatment group during May and June in both the years of treatment (p < 0.02). Only two mild local adverse events were reported in the active group and none was reported in the placebo group.\n The results of this study show that the allergoid SLIT is safe and effective in decreasing symptom scores and drug use in rhinitic patients allergic to grass pollen.", "Specific immunotherapy is the only treatment modality that has the potential to alter the natural course of allergic diseases. Sublingual immunotherapy has been developed to facilitate access to this form of treatment and to minimize serious adverse events.\n To investigate the efficacy and safety of sublingual grass allergen tablets in seasonal allergic rhinoconjunctivitis.\n A multinational, multicenter, randomized, placebo-controlled trial conducted during 2002 and 2003. Fifty-five centers in 8 countries included 855 participants age 18 to 65 years who gave a history of grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense. Participants were randomized to 2500, 25,000, or 75,000 SQ-T grass allergen tablets (GRAZAX; ALK-Abelló, Hørsholm, Denmark) or placebo for sublingual administration once daily. Mean duration of treatment was 18 weeks.\n Average rhinoconjunctivitis scores during the season showed moderate reductions of symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T (P = .0710; P = .0470) compared with placebo. Significantly better rhinoconjunctivitis quality of life scores (P = .006) and an increased number of well days (P = .041) were also observed. Efficacy was increased in the subgroup of patients who completed the recommended preseasonal treatment of at least 8 weeks before the grass pollen season (symptoms, 21%, P = .0020; and medication use, 29%, P = .0120). No safety concerns were observed.\n This study confirms dose-dependent efficacy of the grass allergen tablet. Although further studies are required, the greater tolerability of the tablet may permit immunotherapy to be available to a much broader group of patients with impaired quality of life caused by grass pollen allergy.\n For patients with grass pollen allergy, sublingual immunotherapy is well tolerated and can reduce symptoms and improve quality of life.", "Sublingual immunotherapy (SLIT) is accepted as a safe and effective route for the treatment of grass pollen allergy, but clarification of its clinical and biological efficacy requires more study.\n To evaluate the efficacy, safety, and compliance of SLIT with a standardized 3-grass pollen extract in patients with grass pollen seasonal allergic rhinoconjunctivitis, with or without mild asthma.\n This multicenter, randomized, double-blind study included 127 patients (aged 12-41 years; mean age, 24.9 years) with grass pollen seasonal allergic rhinoconjunctivitis, with or without mild asthma. They received either SLIT with a high-dose, standardized, 3-grass pollen extract or placebo for 10 months before and during the grass pollen season. The efficacy evaluation compared weekly clinical scores (defined as the sum of the symptom score and rescue medication score) to measure rhinoconjunctivitis and asthma for the first 8 weeks of the pollen season. We also evaluated safety and compliance and measured changes in anti-Dactylis specific IgG4 antibody levels.\n There was a trend in favor of the study group in the mean adjusted clinical score. The groups were not comparable on inclusion (P = .02): the SLIT group included more subjects with asthma and had a higher mean IgG4 serum level. Additional exploration according to subgroups with and without asthma found that among the patients without asthma, the SLIT group had a significantly better clinical score (P = .045). Anti-Dactylis specific IgG4 levels increased significantly in the SLIT group.\n SLIT with a standardized, high-dose, 3-grass pollen extract is safe and significantly improves the clinical score in patients with hay fever and without asthma during the pollen season.", "A double-blind, placebo-controlled study of immunotherapy was conducted in 31 patients with allergic rhinitis due to Parietaria pollen to evaluate the efficacy and safety of high doses of allergen via the sublingual route. The patients were assessed before and after a 10-month period of treatment by clinical (symptom-medication scores and specific nasal reactivity) and immunological (total IgE, specific IgE, IgG and IgG4 antibodies) parameters. High doses of Parietaria extract corresponding to a cumulative dose of 105 BU for each patient were administered with negligible side effects. The actively treated patients had significantly lower medication scores than those on placebo (p < 0.05) when the maximum pollen count was recorded, and at the end of the trial they showed a significant decrease in nasal reactivity (p < 0.02) and a significant increase in serum specific IgG4 (p = 0.02). No differences were detected in any of these parameters in the placebo group. Possible explanations for the mechanisms of sublingual immunotherapy are proposed.", "Sublingual-swallow immunotherapy was recently recognized in the World Health Organization Position Paper (Allergen immunotherapy: therapeutic vaccines for allergic diseases) \"as a viable alternative to parenteral injection therapy to treat allergic diseases\" in adults. More controlled studies were required to assess the efficacy and safety of this treatment in children.\n This study was carried out to assess the clinical efficacy and safety profile of sublingual-swallow immunotherapy with high-dose allergen in children with allergies.\n We used a double-blind placebo-controlled design. Forty-one children with Parietaria -induced rhinoconjunctivitis were randomized to receive sublingual standardized Parietaria judaica extract (n = 20) or placebo (n = 21) for 2 years. The cumulative dose of allergen was 375 times higher than that used in parenteral immunotherapy and the cumulative dose of Par j 1 major allergen was 52.5 mg over 2 years. The main efficacy assessment criteria were symptoms and rescue medication scores recorded on the patients' diary cards. Secondary criteria were changes in skin and conjunctival specific reactivity as well as blood parameters, analyzed after 1 and 2 years of immunotherapy. The safety of the treatment was assessed by evaluating the frequency and severity of adverse effects.\n A significant reduction in rhinitis symptoms was observed in the active treatment group during the second season (P =.02), with no difference in medication scores. A significant decrease in skin reactivity (P =.002 after 2 years of treatment) and an increase in the threshold dose for conjunctival allergen provocation test (P =.02) were observed in the active treatment group compared with the group receiving placebo. A significant increase in specific IgG(4 ) levels (P =.02) was also observed in the active group. Immunotherapy was well tolerated.\n Sublingual-swallow immunotherapy in Parietaria -allergic children provided a clinical benefit and a decreased specific reactivity to the allergen. The safety profile of this treatment, which constitutes an important issue, indicated good tolerance and compliance.", "The efficacy and safety of the 300-index of reactivity (IR) dose of 5-grass-pollen sublingual immunotherapy (SLIT) tablets (Stallergènes, Antony, France) have been demonstrated for the treatment of hay fever in adults.\n We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen-related allergic rhinitis.\n In this multinational, randomized, double-blind, placebo-controlled study, 278 children (5-17 years of age) with grass pollen-related rhinoconjunctivitis (confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement) received once-daily SLIT tablets or placebo. Treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was the rhinoconjunctivitis total symptom score (RTSS), a sum of 6 individual symptom scores: sneezing, runny nose, itchy nose, nasal congestion, watery eyes, and itchy eyes. Secondary end points included rescue medication intake, individual scores, and safety.\n The intent-to-treat population included 266 children (mean age, 10.9 +/- 3.22 years). The RTSS for the 300-IR group was highly significantly different from that of the placebo group (P = .001). The 300-IR group showed a mean improvement for the RTSS of 28.0% over that seen with placebo and a median improvement of 39.3%. Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season (P = .0064 and P = .0146, respectively). Adverse events were generally mild or moderate in intensity and expected. No serious side effects were reported.\n Five-grass-pollen SLIT tablets (300 IR) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen-related rhinoconjunctivitis.", "Local application of allergen extracts in specific immunotherapy is accompanied by increased compliance and significantly reduced side effects. However, efficacy of local immunotherapy in children has yet not been sufficiently demonstrated. This study was performed to determine clinical efficacy of high dose sublingual swallow immunotherapy (SLIT) by a double-blind placebo-controlled study in children with grass pollen allergy using high dose allergen extracts.\n A total of 161 children with seasonal rhinoconjunctivitis of which, 68 had also asthma symptoms were enrolled in a multicenter double-blind placebo-controlled study for 1 year and treated on a daily basis with sublingually applied allergen drops. After 1 year all children were given treatment for another 2 years in an open-controlled setting. Symptom scores and medication were assessed during the pollen seasons with structured interviews. Applied allergen dosage, compliance, and side effects were documented by daily diary cards. Primary endpoint was a clinical index (CI) combining symptom scores with medication index. Titrated skin prick tests (SPT) and specific antibody measurements were performed each year.\n Combining symptom with medication scores to CI was highly reliable (reliability coefficient = 0.89, standard error = 9.6%). Allergen-specific IgE- and IgG-subclass antibodies increased significantly in patients treated with SLIT indicating an activation of the immune response induced by the locally applied grass pollen extract. SPT reactivity did not change during therapy. After 1 year of SLIT in the original design we observed no significant difference in the CI between treatment and placebo analyzing all patients included in the study per intention to treat and per protocol. However, subgroup analysis in a repeated measures model revealed that patients with SLIT and severe symptoms before the beginning of treatment (CI > mean/ > 1.51) showed a significant improvement of clinical symptoms after 3 years.\n In this study SLIT was accompanied by a significant placebo effect. Efficacy of treatment could only be seen in children with severe clinical symptoms and this became clinically marked after 3 years of therapy.", "Because cats are a common pet in many houses and tourist complexes in the Canary Islands, sensitization to cat epithelium is a frequent problem. A total of 19.2% of patients with intrinsic asthma are sensitized to cat epithelium. In the Canary Islands, the percentage of sensitization among patients with a household cat is 18.1%, which higher is higher than in the rest of Spain (11.9). Many patients with extrinsic asthma sensitized to house dust mites undergo conventional subcutaneous immunotherapy but evolution is unsatisfactory due to sensitization to cat epithelium (whether a cat is present or not). The aim of this study was to evaluate the clinical effectiveness of sublingual immunotherapy with extract of cat epithelium in monosensitized patients with perennial allergic rhinitis and/or bronchial asthma. Forty patients monosensitized to cat epithelium were selected. Of these, 20 were administered sublingual immunotherapy and another 20 received placebo. The following evaluation was carried out in both groups: in vivo and in vitro: symptom score, skin tests, nasal challenge with cat epithelium, specific IgE determination, specific IgG4 and eosinophilic cationic protein. After 1 year of treatment the cumulative dose was 3.6 micrograms of Fe ld I, equivalent to 10 ng/drop. Duration of treatment was 365 days. Our conclusions, based on our patients in the Canary Islands, were the following: 1. Sublingual Fel d I therapy is effective after 1 year of treatment. 2. There were no modifications in IgE, eosinophilic cationic protein or skin tests. 3. An increase in IgG4 occurred which was related to clinical improvement. 4. In general, tolerance was good, except in one patient who presented urticaria and sublingual pruritus. 5. In polysensitized patients, sublingual immunotherapy to cat epithelium is complementary to immunotherapy to dermatophagoides.", "The safety and the efficacy of sublingual-swallow immunotherapy (SLIT) in perennial conjunctivitis caused by house dust mite were evaluated in a double-blind, placebo-controlled study including 60 patients for 24 months.\n Patients received either placebo or SLIT with standardized Dermatophagoides pteronyssinus (D.pt.) and D. farinae (D.f.) 50/50 extract. The evaluation of the efficacy of the SLIT was obtained by using standardized D. pteronyssinus (D.pt.) extracts on the antigen-specific conjunctival provocation test (CPT). Specific CPT, skin sensitivity and serum-specific IgE were performed before starting treatment and 6, 12, 18 and 24 months.\n Of the 60 patients included, only 45 completed the study (26 in the active group and 19 in the placebo group, P < 0.05). Two out of 30 (6.6%) patients dropped out because of insufficient efficacy in the active group compared to eight out of 30 (26.6%) in the placebo group (P < 0.05). There was a significant increase in the antigen threshold required to obtain a positive CPT from 8.2 IR [95% confidence interval (CI) 5.9-11.4] at baseline to 21.7 IR (95% CI 15.4-30.4) at 2 years (M24) in the active group, compared to 8.1 IR (95% CI 5.4-12.1) at baseline to 8.1 IR (95% CI 5.1-12.4) at M24 in the placebo group (P < 0.04 for overall treatment difference, P < 10-7 for the time-treatment interaction; repeated measures ANOVA). Differences between groups at individual time points were significant from 18 months on. Despite increased antigen concentrations, CPT scores were lower overall in the active than in the placebo group (P < 0.001). No serious adverse effects were reported.\n SLIT effectively increased the antigenic threshold required to obtain a positive CPT to house-dust mite antigen. Tolerance to and innocuity of SLIT were comparable to previous studies. This could justify recommending SLIT for the preventive treatment of perennial conjunctivitis caused by house dust mites.", "Subcutaneous immunotherapy has been the principal approach of immunotherapy in the treatment of allergic diseases. Several clinical studies with birch, alder or hazel pollen extract conducted as subcutaneous immunotherapy have been published suggesting a well-tolerated and clinically effective treatment. Only a few clinical studies of sublingual immunotherapy (SLIT) with these allergens have been published. This study investigated the clinical efficacy, safety and dose-response relationship of SLIT in children suffering from rhinoconjunctivitis with/without asthma.\n Eighty-eight children (5-15 years) with a history of tree pollen-induced allergic rhinoconjunctivitis with/without seasonal asthma for >or=2 years were included. Allergy to tree pollen was confirmed by positive skin-prick test, positive specific IgE and positive conjunctival provocation test. The extract used was a glycerinated mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa 100,000 SQ-U/ml. Children were randomized into three groups receiving SLIT 5 days a week for up to 18 months; dose group 1: accumulated weekly dose of 24,000 SQ-U; dose group 2: accumulated weekly dose of 200,000 SQ-U; and placebo.\n In the birch pollen season, dose group 2 showed a significant reduction of symptom (P = 0.01) and medication scores (P = 0.04) compared with placebo. Dose group 1 showed a significant reduction of symptom scores (P = 0.03). There were no statistical differences between dose groups 1 and 2. All children tolerated the treatment well.\n SLIT with tree pollen extract provided dose-dependent benefits in tree pollen-allergic children in terms of significantly reduced symptoms and medication use. The treatment was well tolerated.", "The best way to prevent allergy symptoms is to treat the allergic condition. Specific immunotherapy with grass allergen tablets 75,000 SQ-T (Grazax, Phleum pratense, ALK-Abelló) is safe and efficacious in rhinoconjunctivitis patients. As rhinoconjunctivitis often co-exists with asthma, we aimed to confirm safety and efficacy in grass allergic subjects with asthma and rhinoconjunctivitis.\n A randomized, double-blind, placebo-controlled, multicentre trial was performed 10-14 weeks prior to and during the grass pollen season 2004. About 114 subjects were randomized 2 : 1 to grass allergen tablets or placebo. The primary end points were average asthma medication and symptom scores during the grass pollen season, and secondary variables were average rhinoconjunctivitis symptom and medication scores during the grass pollen season. Additionally, number of well days was defined post hoc.\n Differences in asthma medication and symptom scores between the treatment groups were negligible. The mean difference in asthma medication score was below 0.1 and 0.3 for asthma symptom score [a single inhalation of salbutamol (200 microg) was scored 2]. No serious adverse events were reported. A reduction in rhinoconjunctivitis symptom score of 37% (P = 0.004) and a 41% (P = 0.036) reduction in medication score was found in the grass pollen season for subjects treated with the grass allergen tablet compared with placebo. Well days increased by 54% (P = 0.002).\n Self-administration of the grass allergen tablet was safe. The treatment did not impair asthma control and confirmed considerable symptom prevention and reduced medication use. It addresses the allergic condition and represents a baseline treatment for grass pollen allergy.", "Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking.\n The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX, ALK-Abelló, Hørsholm, Denmark) compared with placebo in patients with seasonal rhinoconjunctivitis.\n A longitudinal, double-blind, placebo-controlled, parallel-group study that included 51 centers from 8 countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE) were included in the study. Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season.\n The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic adverse events.\n Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis. The tablet was well tolerated with minor local side effects.\n The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use.", "Sublingual immunotherapy (SLIT) has been recognized as a viable alternative to subcutaneous immunotherapy for respiratory allergies both in adults and children, but clinical documentation about safety and efficacy in children is still poor. The purpose of this study was to assess the efficacy and tolerance of SLIT in children who are sensitized to grass pollen.\n Children with a clinical history of intermittent rhinoconjunctivitis, with or without mild asthma and positive skin prick tests to grass pollen, were selected to participate in a 2-year double-blind, placebo-controlled study with SLIT, using a grass extract (ALK-Abellò).\n 22 children were analyzed at the end of the study. No relevant side effects occurred in the active group. A statistically significant difference (p = 0.05; Mann-Whitney test) in favor of the active group (n = 10) could be shown for drug consumption during the second year, as well as a significant improvement as compared to the first year of SLIT (p = 0.05; Wilcoxon test).\n Despite the small number of patients, our data suggest that SLIT with a grass pollen extract is well tolerated in children and is able to significantly reduce drug consumption during the second year of treatment. Studies in larger groups of children sensitized to both grass and tree pollens are needed to definitively assess the role of SLIT in intermittent, seasonal rhinitis and pollen asthma.", "Recent studies have demonstrated the efficacy of sublingual-swallow immunotherapy (SLIT) in seasonal and perennial rhinitis. Sublingual administration of solutions is not convenient for all patients. The aim of the study was to evaluate the efficacy and safety of immunotherapy administered sublingually, initially as drops, and then as tablets during maintenance therapy.\n A total of 126 patients with grass-pollen seasonal rhinitis were included in this double-blind, randomized, placebo-controlled trial. During the progression of doses phase, the five-grass extract was given as sublingual drops from 1 to 100 IR/ml. Once the 100 IR dose was reached, the drops were replaced by a single 100-IR sublingual tablet per day.\n Throughout the grass-pollen season, patients in the active treatment group had significantly lower (P < 0.05) total conjunctivitis and ocular redness scores. Rhinitis symptoms were not significantly different between the two groups. Patients given the active treatment were significantly (P < O.02) less likely to have asthma symptoms. The global medication score showed no significant difference between the two groups. A highly significant difference in favor of the active treatment group was seen in inhaled salbutamol use (P < 0.01).\n Clinical benefits achieved during the present study included significant improvements in conjunctivitis symptoms and prevention of asthma symptoms. The overall safety profile of the active treatment (drops or tablets) was good.", "Seasonal allergic rhinitis is common and troublesome. Sublingual immunotherapy (SLIT) has been proposed as an alternative to injection immunotherapy and might offer some advantages if it were effective and practical in a community setting.\n To assess the efficacy and side-effect profile of SLIT in patients with summer hay fever uncontrolled on current standard medication. To assess the feasibility of delivering SLIT in a United Kingdom general practice setting.\n Double-blind, placebo-controlled study in 186 patients with severe summer hay fever identified from 16 United Kingdom general practices. After a baseline year to ensure balanced groups, subjects were randomized, and SLIT was given for 1 or 2 years and compared with placebo. The principal outcome measure was symptoms as recorded on diary cards. Secondary criteria were skin and conjunctival reactivity, allergen-specific IgE and IgG 4 , and the frequency and severity of adverse effects.\n One hundred thirty-six subjects completed the study. After 1 year, no significant differences were found between actively treated subjects and the placebo group. After the second year of therapy, subjects who had received 2 years treatment were 6.8 times more likely to show a reduction in nose running (P <.001) and 2.4 times more likely to have reduced sneezing (P <.05) compared with subjects in the placebo group. Benefits for nasal blockage were found at the peak pollen season and were similar in both actively treated groups.\n Sublingual immunotherapy can be given successfully and safely in the community. High-dose SLIT has beneficial effects on nasal symptoms during the peak pollen season in patients with severe seasonal allergic rhinitis. At least 2 years of treatment with SLIT is required to show a benefit.", "New routes of administering immunotherapy in respiratory allergy are being studied as an alternative to conventional injective immunotherapy. We carried out a study to evaluate the clinical efficacy and effects of sublingual immunotherapy in patients with Parietaria judaica-induced respiratory allergy.\n A double-blind, placebo-controlled design was followed. Thirty patients with P. judaica rhinoconjunctivitis, mild asthma, or both were randomly chosen for sublingual immunotherapy (14 patients) or placebo treatment (16 patients). The patients underwent preseasonal rush induction treatment followed by coseasonal maintenance treatment during the Parietaria pollen season. Symptom and drug scores, as well as specific IgE and specific IgG4, were recorded.\n Significantly lower symptom and drug scores were found (P=0.04), especially during the Parietaria pollination period, in the immunotherapy group. No significant difference in specific IgE and specific IgG4 was detected between the active and placebo groups; a statistically significant increase of specific IgE was detected in both groups (P=0.05). No patient undergoing active sublingual immunotherapy reported local or systemic side-effects.\n Our data suggest that sublingual immunotherapy is both clinically effective and safe in treating patients with Parietaria-induced rhinoconjunctivitis and mild asthma." ]

[ "11377645", "11006365", "16914693" ]

[ "Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study.", "Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group.", "Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes." ]

[ "Interferon beta reduces activity in multiple sclerosis as measured clinically and by magnetic resonance imaging (MRI). We assessed the effect of interferon beta-1a on the occurrence of relapses in patients after first presentation with neurological events, who are at high risk of conversion to clinically definite multiple sclerosis.\n Eligible patients had had a first episode of neurological dysfunction suggesting multiple sclerosis within the previous 3 months and had strongly suggestive brain MRI findings. Patients were randomly assigned interferon beta-1a 22 microg or placebo subcutaneously once weekly for 2 years. Neurological and clinical assessments were done every 6 months and brain MRI every 12 months. Analyses excluded one patient assigned placebo who received no study injections.\n 241 (78%) of 308 randomised patients received study treatment for 2 years; 278 (90%) remained in the study until termination. 57 (85%) of 67 who stopped therapy did so after conversion to clinically definite multiple sclerosis. Fewer patients developed clinically definite multiple sclerosis in the interferon group than in the placebo group (52/154 [34%] vs 69/154 [45%]; p=0.047). The time at which 30% of patients had converted to clinically definite multiple sclerosis was 569 days in the interferon group and 252 in the placebo group (p=0.034). The annual relapse rates were 0.33 and 0.43 (p=0.045). The number of new T2-weighted MRI lesions and the increase in lesion burden were significantly lower with active treatment.\n Interferon beta-1a treatment at an early stage of multiple sclerosis had significant positive effects on clinical and MRI outcomes.", "Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value.\n We conducted a randomized, double-blind trial of 383 patients who had a first acute clinical demyelinating event (optic neuritis, incomplete transverse myelitis, or brain-stem or cerebellar syndrome) and evidence of prior subclinical demyelination on magnetic resonance imaging (MRI) of the brain. After initial treatment with corticosteroids, 193 patients were randomly assigned to receive weekly intramuscular injections of 30 microg of interferon beta-1a and 190 were assigned to receive weekly injections of placebo. The study end points were the development of clinically definite multiple sclerosis and changes in findings on MRI of the brain. The trial was stopped after a preplanned interim efficacy analysis.\n During three years of follow-up, the cumulative probability of the development of clinically definite multiple sclerosis was significantly lower in the interferon beta-1a group than in the placebo group (rate ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.002). As compared with the patients in the placebo group, patients in the interferon beta-1a group had a relative reduction in the volume of brain lesions (P<0.001), fewer new or enlarging lesions (P<0.001), and fewer gadolinium-enhancing lesions (P<0.001) at 18 months.\n Initiating treatment with interferon beta-1a at the time of a first demyelinating event is beneficial for patients with brain lesions on MRI that indicate a high risk of clinically definite multiple sclerosis.", "To assess efficacy, safety, and tolerability of every-other-day interferon beta-1b treatment in patients with a first clinical event suggestive of multiple sclerosis (MS) (clinically isolated syndrome).\n We conducted a multicenter, randomized, double-blind, placebo-controlled trial. Patients with a first clinical demyelinating event and at least two clinically silent brain MRI lesions were randomized to interferon beta-1b (IFNB-1b) 250 mug subcutaneously (SC) every other day (EOD) (n = 292) or placebo (n = 176), until clinically definite MS (CDMS) was diagnosed or they had been followed for 24 months.\n After 2 years, 45% of placebo patients had converted to CDMS (Kaplan-Meier estimate; primary outcome measure) and 85% fulfilled the McDonald criteria (co-primary outcome measure). Overall interferon beta-1b delayed the time to diagnosis of CDMS (p < 0.0001) and McDonald MS (p < 0.00001). Hazard ratios (95% CI) were 0.50 (0.36 to 0.70) for CDMS and 0.54 (0.43 to 0.67) for McDonald MS favoring treatment with IFNB-1b. Treatment was well tolerated, as indicated by the low rate of patients dropping out of the study before CDMS was reached (6.6% overall, 7.2% in the IFNB-1b group).\n Interferon beta-1b 250 mug subcutaneously every other day delayed conversion to clinically definite multiple sclerosis, and should be considered as a therapeutic option in patients presenting with a first clinical event suggestive of multiple sclerosis." ]

[ "21996593", "19574798", "15760322", "21263100", "18632105" ]

[ "Comparison of pulsed actinomycin D versus 5-day methotrexate for the treatment of low-risk gestational trophoblastic disease.", "Actinomycin d versus methotrexate-folinic acid as the treatment of stage I, low-risk gestational trophoblastic neoplasia: a randomized controlled trial.", "Comparison of pulse methotrexate and pulse dactinomycin in the treatment of low-risk gestational trophoblastic neoplasia.", "Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study.", "Pulse methotrexate versus pulse actinomycin D in the treatment of low-risk gestational trophoblastic neoplasia." ]

[ "To determine the effectiveness of 2 standard chemotherapy regimens for low-risk gestational trophoblastic disease according to the International Federation of Gynecology and Obstetrics (FIGO) staging system.\n From 2008 until 2010, 75 women with low-risk gestational trophoblastic disease received either pulsed actinomycin D (n=50) or 5-day methotrexate (n=25). The primary remission rate, the duration of treatment, the number of treatment courses, and the adverse effects were compared.\n The complete remission rates were 90% for the actinomycin D group and 68% for the methotrexate group (P=0.018). The mean number of chemotherapy courses administered to achieve complete remission (including courses of second-line therapy) was 3.1 in the methotrexate group and 5.3 in the actinomycin D group (P=0.01). No major adverse effects were experienced in either treatment group and there were no significant differences in terms of adverse effects. Second-line chemotherapy was indicated for 11 patients.\n Based on the present study, pulsed actinomycin D seems to be an appropriate first-line treatment for patients with low-risk gestational trophoblastic disease.\n Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.", "This study is to compare the remission and complication rates of actinomycin D (Act-D) and methotrexate-folinic acid (MTX-FA) as single-agent treatments of stage I, low-risk gestational trophoblastic neoplasia (GTN). From 1994 to 2005, all women with International Federation of Gynecology and Obstetrics stage I, low-risk GTN were randomly assigned to received either intravenous Act-D 10 microg/kg per day for 5 days every 2 weeks or intramuscular methotrexate 1 mg/kg per day on days 1, 3, 5, and 7 with intramuscular folinic acid 0.1 mg/kg per day on days 2, 4, 6, and 8 every 2 weeks. Forty-nine women met the eligibility criteria. Age, human chorionic gonadotropin level, and International Federation of Gynecology and Obstetrics score were similar in both treatment groups. Of the 22 women who received Act-D, 2 were lost to follow-up. Among the 27 women who received MTX-FA, 2 were lost to follow-up, and 6 had to switch to Act-D because of the rising levels of liver enzymes. All 20 women (100%) in the Act-D arm achieved remission compared with 14 (73.6%) in 19 women in the MTX-FA arm (P = 0.02). Mucositis and alopecia were reported more frequently in the Act-D group, whereas elevations of liver enzyme levels were more frequent in the MTX-FA group. Actinomycin D seems to be more effective than MTX-FA in the treatment of stage I, low-risk GTN. Larger multicenter randomized controlled trials should be conducted to establish the most appropriate regimen for these patients.", "Methotrexate and dactinomycin are efficient drugs in the treatment of patients with low-risk gestational trophoblastic neoplasia (LRGTN). To compare the effectiveness of these two drugs in LRGTN, 46 patients were randomised to receive weekly intramuscular methotrexate at 30 mg/m(2) (n = 28) or intravenous dactinomycin at 1.25 mg/m(2) every 2 weeks (n = 18). Fourteen patients (50%) in the methotrexate group and 16 patients (89%) in the dactinomycin group achieved complete response. Greater patient convenience and a lower number of required visits make dactinomycin superior to other alternatives.", "There is no consensus on the best regimen for the primary treatment of low-risk gestational trophoblastic neoplasia (GTN).\n Two commonly used single-drug regimens were compared with respect to the proportion of patients meeting the criteria for a complete response (CR) in a randomized phase III trial conducted by the Gynecologic Oncology Group. Eligibility was purposefully broad to maximize the generalizability of the results and included patients with a WHO risk score of 0 to 6 and patients with metastatic disease (limited to lung lesions < 2 cm, adnexa, or vagina) or choriocarcinoma.\n Two hundred forty women were enrolled, and 216 were deemed eligible. Biweekly intravenous dactinomycin 1.25 mg/m² was statistically superior to weekly intramuscular (IM) methotrexate 30 mg/m² (CR: 70% v 53%; P = .01). Similarly, in patients with low-risk GTN as defined before the 2002 WHO risk score revisions (risk score of 0 to 4 and excluding choriocarcinoma), response was 58% and 73% in the methotrexate and dactinomycin arms, respectively (P = .03). Both regimens were less effective if the WHO risk score was 5 or 6 or if the diagnosis was choriocarcinoma (CR: 9% and 42%, respectively). There were two potential recurrences; one at 4 months (dactinomycin) and one at 22 months (methotrexate). Not all patients completed follow-up. Both regimens were well tolerated.\n The biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN, a generally curable disease.", "To compare the efficacy of methotrexate and actinomycin D as single agents in first-line chemotherapy for women with low-risk gestational trophoblastic neoplasia (LR-GTN).\n A total of 131 women with LR-GTN were randomized to receive a weekly pulsed dose of 30 mg/m(2) of methotrexate intramuscularly (n=81) or a pulsed intravenous bolus of 1.25 mg/m(2) of actinomycin D every 2 weeks (n=50). An additional cycle was administered as consolidation treatment following normalization of the serum level of beta-human chorionic gonadotropin (<5 IU/L).\n Complete remission was achieved in 48.14% of patients in the methotrexate group and 90.00% in the actinomycin D group (P<0.001). The mean number of treatment cycles needed to achieve response was lower in the actinomycin D group (4.8 vs 6.8). The risk of treatment failure was 26.4 greater with methotrexate than with actinomycin D (95% confidence interval, 5.7-22.6; P<0.001).\n Actinomycin D may be a better option than methotrexate as a first-line chemotherapy agent for patients with LR-GTN." ]

[ "1297051", "16477114", "10633593", "15281672", "11515325", "7381613", "402445", "16532873", "10025022" ]

[ "Histamine provocation test: an effective pre-employment selection method for aluminium workers.", "A study of the effects of isokinetic pre-employment physical capability screening in the reduction of musculoskeletal disorders in a labor intensive work environment.", "Preplacement assessments. Impact on injury outcomes.", "A comparison between two systems for pre-employment medical assessment in the Royal Netherlands Army by a randomized, controlled study.", "Preassignment examination for personnel on Iwo Jima.", "Isometric strength testing as a means of controlling medical incidents on strenuous jobs.", "The value of preplacement medical examinations for nonhazardous light duty work.", "Increasing the physical fitness of low-fit recruits before basic combat training: an evaluation of fitness, injuries, and training outcomes.", "The effects of prework functional screening on lowering an employer's injury rate, medical costs, and lost work days." ]

[ "A descriptive study was made at a primary aluminium smelter to find evidence of the efficiency of the Histamine Provocation Test as part of a pre-employment examination. 174 cases of potroom asthma were divided into two groups. 157 cases were employed in the years 1970-1981. The second group consisted of 17 men who were employed after the introduction of the HPT in 1982. The urinary fluoride levels showed a lowering in exposure to fluorides during the last five years. Medical data collected at the pre-employment examination was compared between the two groups. There were significantly more smokers in the first group of 157 men. Bronchitis or asthma during childhood was mentioned by many men in the second group. It is concluded that the HPT played an important role in the attempt to reduce the incidence of potroom asthma, followed by greater attention to working conditions.", "This study investigated the effects of pre-employment physical ability screening using isokinetic dynamometry in injury development, specific to musculoskeletal disorders (MSDs) of the knees, shoulders and back among workers in physically demanding jobs.\n New hires (n=503) from a large US employer's 105 industrial yards were screened to match the physical demands of their prospective jobs and tracked for up to 33 months. Results were compared to a control group of 1423 workers.\n There were significant reductions in the frequency and severity of musculoskeletal disorder injuries in the screened employee population. Non-screened applicants were 2.38 times more likely to experience a MSD-related overexertion injury specific to the knees, shoulders and back than screened hires (OR=2.3759; p=0.0001), and incurred 4.33 times higher cost of claims (p=0.0003). Covariates of age, pay type, race and job classification were markedly different between screened and unscreened hires. Among the screened cohort, only the more physically demanding job classifications were significant with field material handlers 7.1 times more likely to experience a non-MSD than less physically demanding workers (OR=7.1036; p=0.0063).\n Objective isokinetic pre-employment screening may significantly reduce injuries in physically demanding jobs. Employees having been effectively matched to the physical demands of their jobs may be at significantly lesser risk of injury and disability from both musculoskeletal and non-musculoskeletal disorders.", "Evaluation of the impact of preplacement assessments is important given the resources companies and occupational health nurses allocate to screening and the ambiguity of the literature about the effectiveness of such assessments. This study examined the effects of preplacement assessments on employee injuries. All individuals screened by an occupational health clinic in the upper Midwest and given work restrictions during a 3 year period were identified as cases (n = 67). Cases were matched with controls without work restrictions (n = 264) on the basis of employer, gender, and job. Age was controlled for statistically. Chi-square analysis, used to test differences in percent distribution of injuries between cases and controls, found no statistically significant differences in musculoskeletal injuries between the groups. Work restrictions recommended as a result of preplacement assessments appear to protect vulnerable workers.", "In 1998, the basic medical requirements for the Royal Netherlands Army were introduced as a standard for the assessment of the medical suitability of military personnel, consisting of 43 dichotomized points of judgment. This system replaced the old physical capacity, upper limbs, locomotion, hearing, eyesight, and emotional and mental state system, based on the detection of diseases and infirmities. We compared the two different examination systems for their ability to identify suitable recruits. For the latter purpose, we used the two operational measures of availability and health care costs. We performed a randomized, controlled study in which 352 soldiers were monitored for 2 years after being declared fit by one of the pre-employment medical assessment systems in question and having passed their general military training. We found that the pre-employment medical assessment system was the dominant factor for predicting the number of days fit-for-duty, as well as for the health care costs incurred. Those declared fit by the new system showed a statistically significant higher mean number of days fit-for-duty (648 compared with 612) and incurred significantly lower mean health care costs (6396 compared with 746 Euro). In this study, we were not able to uncover the mechanism by which the \"basic medical requirements\" examination system led to an improvement in outcome. For the present, this mechanism is interpreted because of differences between the two systems.", "The Japan Maritime Self-Defense Force (JMSDF) requires all personnel assigned to Iwo Jima to undergo a preassignment medical examination. The efficacy and benefit of this mandatory examination has not been evaluated objectively in depth. Our purpose was to review the health status of JMSDF personnel assigned to Iwo Jima and to evaluate the correlation of the preassignment medical examination to their current health status for the study period. We divided the participants into two groups. Group Y was composed of JMSDF personnel receiving a preassignment medical examination, and group N was composed of those personnel who did not receive the examination. After the annual health examination, health status was evaluated using objective criteria. We found little statistically significant difference among group Y and group N participants. However, proportionally more patients currently receiving care for or diagnosed with hypertension, hyperuricemia, or severe obesity were identified as being members of group N than group Y. We have demonstrated that the preassignment medical examination may contribute to predicting the health status of potential Iwo Jima personnel and may contribute to controlling the cost of care associated with these specific diagnoses by limiting the assignment of at-risk personnel.", "This investigation was performed to determine if isometric strength tests can be used to select workers for strenuous jobs and to reduce occupational injuries which are caused by a mismatch between worker strength and job strength requirements. Twenty jobs in a tire and rubber plant were studied biomechanically to identify critical strength-demanding tasks. Four strength tests were designed to simulate these tasks, and performance criteria were established for passing the tests. New applicants were administered the tests during their preplacement examinations to determine if they possessed sufficient strength to qualify for the jobs. The medical incidence rate of employees who were selected using the strength tests was approximately one-third that of employees selected using traditional medical criteria. It was concluded that isometric strength tests can be used to reduce occupational injuries and should be considered for implementation in industries with strenuous jobs.", "A prospective study on 6,125 job applicants for light duty telephone company work is presented, which indicates that a preplacement medical evaluation is not predictive of risks relating to work attendance or job performance in nonhazardous assignments. Results show that between groups of employees, who were medically classified at the time of hire into categories with or without employment risk factors, there was no significant difference relative to sickness, accident or other absence, or to work performance during the first twelve months after hire. A work force loss of 25% is seen during the first year after hire without significant difference between groups for either numbers of employees lost or reason for loss. A cost-benefit analysis based on this study is presented, which demonstrates that the preplacement medical evaluation for light duty assignments is not cost effective. In addition, further unnecessary costs are incurred when job applicants are medically evaluated but not hired, which is shown to occur here for 27.5% of healthy applicants.", "Recruits arriving for basic combat training (BCT) between October 1999 and May 2004 were administered an entry-level physical fitness test at the reception station. If they failed the test, then they entered the Fitness Assessment Program (FAP), where they physically trained until they passed the test and subsequently entered BCT. The effectiveness of the FAP was evaluated by examining fitness, injury, and training outcomes. Recruits who failed the test, trained in the FAP, and entered BCT after passing the test were designated the preconditioning (PC) group (64 men and 94 women). Recruits who failed the test but were allowed to enter BCT without going into the FAP were called the no preconditioning (NPC) group (32 men and 73 women). Recruits who passed the test and directly entered BCT were designated the no need of preconditioning (NNPC) group (1,078 men and 731 women). Army Physical Fitness Test (APFT) scores and training outcomes were obtained from a company-level database, and injured recruits were identified from cases documented in medical records. The proportions of NPC, PC, and NNPC recruits who completed the 9-week BCT cycle were 59%, 83%, and 87% for men (p < 0.01) and 52%, 69%, and 78% for women (p < 0.01), respectively. Because of attrition, only 63% of the NPC group took the week 7 APFT, compared with 84% and 86% of the PC and NNPC groups, respectively. The proportions of NPC, PC, and NNPC recruits who passed the final APFT after all retakes were 88%, 92%, and 98% for men (p < 0.01) and 89%, 92%, and 97% for women (p < 0.01), respectively. Compared with NNPC men, injury risk was 1.5 (95% confidence interval, 1.0-2.2) and 1.7 (95% confidence interval, 1.0-3.1) times higher for PC and NPC men, respectively. Compared with NNPC women, injury risk was 1.2 (95% confidence interval, 0.9-1.6) and 1.5 (95% confidence interval, 1.1-2.1) times higher for PC and NPC women, respectively. This program evaluation showed that low-fit recruits who preconditioned before BCT had reduced attrition and tended to have lower injury risk, compared with recruits of similar low fitness who did not precondition.", "The data in this study were gathered retrospectively after the progress of program development in terms of employee outcomes within an organization. This design characterizes a retrospective longitudinal study.\n To determine whether prework functional screens are effective in lowering the incidence of work-related back sprains or strains, related medical costs, and lost work days within an organization.\n Musculoskeletal injuries are considered the leading cause of disability for people during their working years. Back injuries are the most common reason for workers' decreased work capacity and reduced leisure time. The increased rate of injury and escalating workers' compensation costs are are a major force motivating companies to implement a tool that can be effective in lowering back sprain or strain injuries and containing their workers' compensation costs. The U.S. Department of Health and Human Services reports a major objective of increasing the number of companies offering back injury prevention programs by the year 2000.\n The study follows the effects realized when a medical center institutes close case management, early return to work policies, and prework functional screens in three stages over the course of 10.5 years.\n The severity of back sprains or strains, related medical costs, and lost work days were significantly lower with the use of prework functional screens on all new employees hired into physically laborious jobs.\n This study offers employers a proven effective tool that can be used to help lower the severity of on-the-job back sprains or strains, resulting medical costs, and lost work days in their organization." ]

[ "4980886", "17894080", "4550211", "344086", "4605009", "4053", "4860981", "334315", "4556089" ]

[ "A controlled evaluation of haloperidol, chlorpromazine, and sodium amobarbital: intramuscular short-term use in acute psychotic patients.", "Parenteral haloperidol for rapid control of severe, disruptive symptoms of acute schizophrenia.", "Haloperidol, clopenthixol, and chlorpromazine in chronic schizophrenia. Chemically unrelated antipsychotics as therapeutic alternatives.", "A comparison of the relative efficacy of Serenace and chlorpromazine in the treatment of chronic schizophrenics.", "Rapid tranquilization of acutely psychotic patients with intramuscular haloperidol and chlorpromazine.", "Tranquilizers or anti-depressants for chronic schizophrenics: a long term study.", "Effects of two butyrophenone compounds on acute schizophrenic patients: speculation on the neurophysiologic sites of action.", "High dosage haloperidol in chronic schizophrenia.", "Comparison of injectable haloperidol and chlorpromazine." ]

[ "nan", "Intramuscular haloperidol, at three dose levels, (5 mg, 2 mg, and 1 mg) chlorpromazine (25 mg), and placebo were compared for efficacy, rapidity of therapeutic onset, and safety in 50 acute psychotic patients requiring rapid control. The drugs were administered parenterally under double-blind conditions at half-hour intervals until successful control of moderate to very severe symptomatology was achieved or a maximum of four injections had been given. Global evaluation, BPRS, and target symptom ratings were performed. The overall results indicated that the 5 mg and 2 mg haloperidol doses were significantly superior to the 1 mg haloperidol and 25 mg chlorpromazine doses and to placebo. Transfer of patients to oral haloperidol was satisfactorily accomplished. Side effects for all medications were minimal and included slight to moderate EPS and drowsiness. The use of antiparkinson drugs completely controlled the extrapyramidal symptoms.", "nan", "A study designed to assess the relative efficacy of chlorpromazine and Serenace in the control of chronic schizophrenics is described. Twenty-five cases were selected for the study and were randomly allocated to treatment. The condition of the patients was assessed at fortnightly intervals over the eight-week duration of trial period. No significant differences in side-effects emerged in patients on chlorpromazine and Serenace in the dosages administered. The statistically significant trends all showed a superiority of Serenace above chlorpromazine which was in accord with the clinical picture.", "nan", "The relative efficacy of 4 tranquilizers was investigated in 66 chronic schizophrenics who had been hospitalized for 10.01 years (mean). The role of adding an anti-depressant was also studied. Following a 4 week placebo period, high dosage tranquilizers were given for 16 weeks and amitriptyline was added for the following 16 weeks. Statistical analyses of the various change measures revealed that patients worsened significantly on placebo, all 4 tranquilizers were significantly better than placebo for symptom reduction and maximum improvement was attained within 16 weeks of tranquilizer administration. No significant differences in efficacy were observed among the 4 tranquilizers and addition of amitriptyline did not confer any additional therapeutic advantage.", "nan", "In a double blind chlorpromazine-controlled trial, high dosage haloperidol (100 mg daily) given for three months, appreciably improved the mental state of male chronic 'drug resistant' schizophrenic inpatients in the rehabilitation/long-stay unit of one psychiatric hospital. The results of a three-month follow-up suggested that the improvement could be maintained in some patients on lower doses of the drug. Serious extrapyramidal side effects were not seen at high doses. However, the majority of patients on haloperidol showed a deterioration in ward behaviour, possibly related to drowsiness, and developed raised serum alkaline phosphatase levels. These side effects disappeared in the follow-up period when either the drug was discontinued or the dose of haloperidol reduced.", "nan" ]

[ "15302725", "7149451", "11207014", "8222813" ]

[ "Inspiratory muscle training improves lung function and exercise capacity in adults with cystic fibrosis.", "The effects of inspiratory muscle training in patients with cystic fibrosis.", "Inspiratory muscle training in patients with cystic fibrosis.", "Improved pulmonary function and exercise tolerance with inspiratory muscle conditioning in children with cystic fibrosis." ]

[ "To investigate the effects of high-intensity inspiratory muscle training (IMT) on inspiratory muscle function (IMF), diaphragm thickness, lung function, physical work capacity (PWC), and psychosocial status in patients with cystic fibrosis (CF).\n Twenty-nine adult patients with CF were randomly assigned to three groups. Two groups were required to complete an 8-week program of IMT in which the training intensity was set at either 80% of maximal effort (group 1; 9 patients) or 20% of maximal effort (group 2; 10 patients). A third group of patients did not participate in any form of training and acted as a control group (group 3; 10 patients).\n In all patients, baseline and postintervention measures of IMF were determined by maximal inspiratory pressure (Pimax), and sustained Pimax (SPimax); pulmonary function, body composition, and physical activity status were also determined. In addition, diaphragm thickness was measured at functional residual capacity (FRC) and total lung capacity (TLC) [TDIcont], and the diaphragm thickening ratio (TR) was calculated (TR = thickness during Pimax at FRC/mean thickness at FRC). Subjects also completed an incremental cycle ergometer test to exhaustion and two symptom-related questionnaires, prior to and following training.\n Following training, significant increases in Pimax and SPimax (p < 0.05), TDIcont (p < 0.05), TR (p < 0.05), vital capacity (p < 0.05), TLC (p < 0.05), and PWC (p < 0.05) were identified, and decreases in anxiety scores (p < 0.05) and depression scores (p < 0.01) were noted in group 1 patients compared to group 3 patients. Group 2 patients significantly improved Pimax and SPimax (both p < 0.05) only with respect to group 3 patients. No significant differences were observed in group 3 patients.\n An 8-week program of high-intensity IMT resulted in significant benefits for CF patients, which included increased IMF and thickness of the diaphragm (during contraction), improved lung volumes, increased PWC, and improved psychosocial status.", "This study evaluated whether inspiratory muscle training (IMT) could increase inspiratory muscle strength and endurance and exercise performance in 11 patients with cystic fibrosis (CF) with moderately severe airflow limitation. The IMT consisted of breathing through an inspiratory resistance (IR) for 15 min twice daily for 4 wk, preceded or followed by a 4-wk control period. After IMT, there was an increase in inspiratory muscle strength measured by maximal inspiratory mouth pressure at functional residual capacity: 74 +/- 18 cmH2O before training to 81 +/- 12 cmH2O after training, mean +/- 1 SD, p less than 0.025, and in inspiratory muscle endurance measured by the maximal IR tolerated for 10 min. Limitation of performance in the progressive exercise test was related to increased airflow limitation and possibly to poor nutrition. Mean exercise performance during progressive or submaximal exercise testing did not change after training. It is concluded that this form of IMT improved inspiratory muscle strength and endurance, but had little effect on exercise performance in patients with CF.", "Little information is available about the effects of inspiratory muscle training in patients with cystic fibrosis (CF). In this study the effects of inspiratory-threshold loading in patients with CF on strength and endurance of the inspiratory muscles, pulmonary function, exercise capacity, dyspnoea and fatigue were evaluated. Sixteen patients were assigned to one of two groups using the minimization method: eight patients in the training group and eight patients in the control group. The training was performed using an inspiratory-threshold loading device. Patients were instructed to use the threshold trainer 20 min a day, 5 days a week for 6 weeks. Patients in the training group trained at inspiratory threshold loads up to 40% of maximal static inspiratory pressure (Pimax) and patients in the control group got 'sham' training at a load of 10% of Pimax. No significant differences were found among the two groups in gender, age, weight, height, pulmonary function, exercise capacity, inspiratory-muscle strength and inspiratory-muscle endurance before starting the training programme. Mean (SD) age in the control group was 19 (5.5) years, mean (SD) age in the training group was 17 (5.2) years. Mean FEV1 in both groups was 70% predicted, mean inspiratory-muscle strength in both groups was above 100% predicted. All patients except one, assigned to the training group, completed the programme. After 6 weeks of training, mean inspiratory-muscle endurance (% Pimax) in the control group increased from 50% to 54% (P = 0.197); in the training group mean inspiratory muscle endurance (% Pimax) increased from 49% to 66% (P = 0.003). Statistical analysis showed that the change in inspiratory-muscle endurance (% Pimax) in the training group was significantly higher than in the control group (P = 0.012). After training, in the training group there was a tendency of improvement in Pimax with an increase from 105 to 123% predicted, which just fell short of statistical significance (P = 0.064). After training no significant differences were found in changes from baseline in pulmonary function, exercise capacity, dyspnoea and fatigue. It is concluded that low-intensity inspiratory-threshold loading at 40% of Pimax was sufficient to elicit an increased inspiratory-muscle endurance in patients with CF.", "This study documented the effect of inspiratory muscle conditioning in children with cystic fibrosis. Subjects, ages 7 to 14 years, were divided into two groups. The experimental group (n = 10) trained at a high pressure load (> or = 29 cm H2O) and the control group (n = 10) trained at a minimal pressure load (< or = 15 cm H2O), using a threshold loading device. Subjects trained 30 min a day for 10 weeks. Pulmonary function, inspiratory muscle strength, and exercise tolerance were measured at the beginning and end of the training period. Pulmonary function was measured by body plethysmography. Inspiratory muscle strength was determined by standard measures of maximal inspiratory pressure against an occluded airway. Exercise tolerance was measured by the length of time subjects could walk on a treadmill. Findings indicated that the experimental group showed significant increases in inspiratory muscle strength, vital capacity, total lung capacity, and exercise tolerance in comparison to the control group." ]

[ "16730488", "19301720", "8633669", "19897857", "16307966", "15541406", "20705153", "17006401", "10966997", "7060371", "19374294", "8982753", "10549449", "12351534", "10962136", "2117517", "12413614", "8982752", "12267101", "22325113", "16284061", "19369294", "16472565", "15451330", "5409835", "14668006", "21213495", "18672110" ]

[ "Efficacy of a selective COX-2 inhibitor for controlling irregular uterine bleeding in DMPA users.", "Efficacy of celecoxib on controlling irregular uterine bleeding secondary to Jadelle use.", "Hormonal treatment for bleeding irregularities in Norplant implant users.", "Randomized placebo-controlled trial of CDB-2914 in new users of a levonorgestrel-releasing intrauterine system shows only short-lived amelioration of unscheduled bleeding.", "Tamoxifen treatment of bleeding irregularities associated with Norplant use.", "Effectiveness and acceptability of vitamin E and low-dose aspirin, alone or in combination, on Norplant-induced prolonged bleeding.", "Vaginal estrogen supplementation during Depo-Provera initiation: a randomized controlled trial.", "Low-dose oral contraceptive to re-induce menstrual bleeding in amenorrheic women on DMPA treatment: a randomized clinical trial.", "Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel.", "Endometrial morphology and peripheral steroid levels in women with and without intermenstrual bleeding during contraception with the 300 microgram norethisterone (NET) minipill.", "The effect of tranexamic acid for treatment irregular uterine bleeding secondary to DMPA use.", "The effect of transdermal oestradiol on bleeding pattern, hormonal profiles and sex steroid receptor distribution in the endometrium of Norplant users.", "The effect of mefenamic acid on controlling irregular uterine bleeding secondary to Norplant use.", "Improving cycle control in progestogen-only contraceptive pill users by intermittent treatment with a new anti-progestogen.", "Benefits of vitamin E supplementation to Norplant users--in vitro and in vivo studies.", "Clinical assessment of treatments for prolonged bleeding in users of Norplant implants.", "Post-abortion depot medroxyprogesterone acetate continuation rates: a randomized trial of cyclic estradiol.", "Oestrogen treatment for increased bleeding in Norplant users: preliminary results.", "[Evaluation of the efficacy of a venotonic capillary protector in the treatment of metrorrhagia due to IUD or micropill contraception].", "Doxycycline in the treatment of bleeding with DMPA: a double-blinded randomized controlled trial.", "A pilot study to assess the effect of three short-term treatments on frequent and/or prolonged bleeding compared to placebo in women using Implanon.", "A randomized controlled trial of treatment options for troublesome uterine bleeding in Implanon users.", "The effect of tranexamic acid for treatment of irregular uterine bleeding secondary to Norplant use.", "Effect of mefenamic acid on controlling irregular uterine bleeding in DMPA users.", "Effect of supplementary oral estrogen on long-acting injectable progestogen contraception.", "Mifepristone for the prevention of breakthrough bleeding in new starters of depo-medroxyprogesterone acetate.", "The effect of mefenamic acid on controlling irregular uterine bleeding second to Implanon use.", "Effects of ethinyl estradiol and ibuprofen compared to placebo on endometrial bleeding, cervical mucus and the postcoital test in levonorgestrel subcutaneous implant users." ]

[ "This double-blind, placebo-controlled study was conducted to evaluate the efficacy of valdecoxib and placebo for controlling irregular uterine bleeding in depot-medroxyprogesterone acetate (DMPA) users.\n A total of 51 DMPA users were enrolled. All subjects in the study had abnormal bleeding and were randomly divided into two groups. One group totaling 22 received valdecoxib, 40 mg, once a day for 5 days, and placebos were given to another 24 in the same manner; 5 subjects dropped out from the study. Analysis of the number of treatment days required for stopping the bleeding episode, percentage of women whose bleeding was stopped in 7 days, total number of bleeding-free days and length of the bleeding-free interval after the initial treatment was determined in the first and the fourth weeks.\n The percentage of the subjects whose bleeding was stopped during the first week after the initial treatment and the mean value of the bleeding-free days during the 28 days of the follow-up period were significantly higher in the valdecoxib group than in the placebo group (77.3% vs. 33.3%, p<.01; and 17.8 days vs. 11.5 days, p<.05, respectively). The mean duration of treatment days required for stopping the bleeding episode in the valdecoxib-treated group was 1.7 days, and the mean duration of the bleeding-free interval in valdecoxib-treated group was 18.6 days.\n Valdecoxib was more effective than placebo in the short-term control of irregular bleeding in DMPA users. The mechanism of nonsteroidal anti-inflammatory drugs (NSAIDs) for the reduction of endometrial bleeding is likely from COX-2 inhibition.", "To evaluate the efficacy of celecoxib and placebo for controlling irregular uterine bleeding in Jadelle users.\n Randomized double blind placebo controlled trial.\n Family Planning Clinic, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.\n Forty Jadelle users with irregular bleeding were randomly allocated into two groups. Twenty users received celecoxib 200 mg once a day for five days and the other twenty users received the placebo in the same manner The participants were requested to maintain their daily record of bleeding, adverse effects, and satisfaction.\n The percentage of the subjects whom bleeding was stopped within 7 days after initial treatment was significantly higher in the celecoxib group than in the placebo group (70% vs. 0%; p < 0.001). The mean duration of bleeding-free interval was significantly longer in celecoxib than placebo group (24.0 +/- 1.65 days vs. 10.0 +/- 6.50 days; p < 0.001). The mean duration of bleeding days was significantly shorter in celecoxib than placebo group (5.0 +/- 1.65 vs. 19.0 +/- 6.50 days; p < 0.001). Patients satisfaction in celecoxib group was significantly higher than the placebo group (80% vs. 30%; p < 0.001). There was no detectable adverse effect in both groups.\n Celecoxib was more effective than placebo in the short-term control of irregular bleeding in Jadelle users. The mechanism of nonsteroidal anti-inflammatory drugs (NSAIDs) for the reduction of endometrial bleeding is likely from COX-2 inhibition.", "Our purpose was to evaluate whether prolonged or irregular bleeding during Norplant implant use could be alleviated with the use of oral hormonal medication.\n One hundred fifty users of the Norplant levonorgestrel contraceptive implant with prolonged or frequent bleeding were enrolled in this prospective, randomized, comparative study and assigned to one of three treatment groups for 20 days: ethinyl estradiol 50 microg, an oral contraceptive (50 microg ethinyl estradiol and 250 microg levonogestrel), and placebo. Total days of bleeding during treatment and length of the bleeding-free interval were analyzed.\n Women treated with the levonorgestrel-ethinyl estradiol pill bled an average of 2.6 days during treatment compared with 5.4 and 12.3 days in the ethinyl estradiol and placebo groups, respectively. Differences between both hormonal groups and placebo were significant (p <0.00001); moreover, the combined pill was more effective than ethinyl estradiol along (p <0.0001).\n The combined pill proved to be an excellent palliative treatment and is a more practical approach because of availability at all clinic sites.", "The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive. However, during early months of use unscheduled vaginal bleeding is common, sometimes leading to discontinuation. This study aimed to determine whether intermittent administration of progesterone receptor modulator CDB-2914 would suppress unscheduled bleeding during the first 4 months after insertion of the LNG-IUS.\n CDB-2914 150 mg, in divided doses, or placebo tablets, were administered over three consecutive days starting on Days 21, 49 and 77 after LNG-IUS insertion, in a double-blind randomized controlled trial of women aged 19-49 years, newly starting use of LNG-IUS. Daily bleeding diaries were completed for 6 months, and summarized across blocks as percentage days bleeding/spotting (BS%).\n Of 69 women randomized to receive CDB-2914, and 67 placebo, 61 and 55, respectively, completed the trial. BS% decreased with time in both arms, but showed a much steeper treatment-phase gradient in the placebo arm (P < 0.0001), so that a benefit of CDB-2914 in the 28 days after first treatment (-11% points, 95% CI -19 to -2), converted to a disadvantage by 64 days after the third treatment (+10% points, 95% CI 1-18).\n The effect of CDB-2914 on BS% was initially beneficial but then by third treatment was disadvantageous. Nevertheless, only 3% (4/136) of all women discontinued LNG-IUS. These findings give insight into possible mechanisms and suggest future research directions. ISRCTN Trial no. ISRCTN58283041; EudraCT no. 2006-006511-72.", "To evaluate the possible role of tamoxifen (selective estrogen receptor modulators, SERM) in treating bleeding irregularities associated with Norplant contraceptive use.\n Randomized clinical trial including 100 Norplant users complaining of vaginal bleeding irregularities. The trial was conducted in the Family Planning Clinic of Assiut University Hospital. Women were assigned at random to receive tamoxifen tablets (10 mg) twice daily for 10 days or similar placebo. Women were followed-up for 3 months. The end points were percentage of women who stopped bleeding during treatment, bleeding/spotting days during the period of follow-up, effect of treatment on their lifestyle, and side effects and discontinuation of contraception.\n There was good compliance with treatment. At the end of treatment, a significantly higher percentage of tamoxifen users stopped bleeding in comparison to the control group (88% vs. 68%, respectively; p=.016). Women who used tamoxifen had significantly less bleeding and/or spotting days than women who used placebo, during the first and second months. During the third month, there were no significant differences between the two groups. Women who used tamoxifen reported improvement in performing household activities, religious duties and in sexual life, during the first 2 months. In the third month, there were no differences between the two groups. There were no significant differences between tamoxifen and placebo groups in reporting side effects. In the group who used tamoxifen, two women discontinued Norplant use because of bleeding vs. nine women in the placebo group.\n Tamoxifen use at a dose of 10 mg twice daily orally, for 10 days, has a beneficial effect on vaginal bleeding associated with Norplant use. In addition, the bleeding pattern was better in women who used tamoxifen for the following 2 months after treatment. However, these results have to be confirmed in a larger trial before advocating this line of treatment.", "A study (ISRCTN 77665712) was undertaken to test the effectiveness and the acceptability of vitamin E and low-dose aspirin, alone or in combination, as treatment for prolonged vaginal bleeding induced by Norplant. A total of 486 Norplant users who were requesting treatment for bleeding lasting longer than 7 days were enrolled in five centers: Beijing, China; Jakarta, Indonesia; Santiago, Chile; Santo Domingo, Dominican Republic; and Tunis, Tunisia. They were randomized to one of four different 10-day oral treatments: 200 mg vitamin E daily, 80 mg aspirin daily, both or a placebo. Treatment packs were designed to ensure blinding of both the subjects and the clinical staff. Neither vitamin E nor low-dose aspirin nor their combination was found to have any effect on reducing the length of the bleeding episode for which treatment was taken or on the vaginal bleeding patterns these women experienced during the year of follow-up.", "Irregular bleeding is often cited as the reason for discontinuation of depot-medroxyprogesterone acetate (DMPA) after the first injection. Estrogen supplementation during DMPA initiation may decrease bleeding and improve continuation.\n This prospective, randomized, controlled trial evaluated estrogen supplementation during DMPA initiation. Women initiating DMPA were randomized to receive an estradiol vaginal ring for 3 months versus DMPA alone. Bleeding diaries and questionnaires at three and 6 months assessed bleeding, continuation and ring acceptability.\n Seventy-one participants enrolled; 49 completed the first follow-up period. The median number of bleeding or spotting days was 16 in the estrogen ring group (n=26) versus 28 in the DMPA alone group (n=23) (p=.19). Seventy-seven percent of the intervention group received a second injection compared with 70% in the DMPA alone group (p=.56). For each additional day of bleeding and/or spotting reported, women were 3% less likely to receive a second injection (OR 0.97, 95% CI 0.94-0.99). Acceptability of the vaginal ring was high among those in the intervention group.\n Vaginal estrogen supplementation during DMPA initiation is acceptable to women and may decrease total bleeding.\n Copyright 2010 Elsevier Inc. All rights reserved.", "Depot medroxy progesterone acetate (DMPA) is one of the most reliable contraceptive methods with a failure rate less than 0.3 percent. It is injected every three months and Although it has many advantages over many other hormonal contraceptives, But a major disadvantage of it is bleeding disorders which comprise most of the discontinuance reasons. Our Aim was to study bleeding complications of DMPA when used as a contraceptive in Ardabil district and clinical trial of LD and Ethynil oestradiol in controlling these complications.\n All the 917 women who referred to ardabil's health centers for having a DMPA injection for the first time, were entered into a longitudinal study. Those complaining of menstrual cessation were entered into a double blinded randomized clinical trial. Data were collected by means of 9 questionnaires 7 of them used for descriptive and 2 for clinical trial study. Data was analyzed by SPSS statistical package.\n Those DMPA users with a cesarean section history had a higher chance of bleeding complications. Four hundred forty-four of the 917 women receiving the injection discontinued using it before the end of the study period. The main reason for discontinuation (in 70%) was irregular menstrual bleedings and menstrual cessation. In the clinical trial of women with bleeding cessation, 70% of those receiving the LD-OC pill experienced menstrual bleedings again, compared with only 22.7% in the placebo group. The discontinuation rate in the drug group was lower than in the placebo group as well (p < 0.05).\n Treating menstrual cessation caused by DMPA with LDs, improves the complication and decreases the discontinuance rate.", "It has been suggested that the administration of an anti-progesterone might improve bleeding patterns in women with irregular bleeding while using low-dose progestin-only contraception. We report the findings of a double-blind, randomized, placebo-controlled trial of mifepristone 50 mg taken once every 4 weeks in 100 Chinese women (50 subjects and 50 controls) complaining of frequent and irregular bleeding while using a levonorgestrel-releasing subdermal contraceptive implant. In all women, regardless of treatment, the frequency of bleeding decreased significantly over 360 days of observation. Women recorded significantly shorter episodes of bleeding (P: < 0.0002) during mifepristone treatment than during the 90 days before treatment started. In contrast, the duration of bleeding episodes fell more gradually in placebo-treated controls. Women using mifepristone were more likely to find treatment acceptable than women receiving a placebo tablet (P: < 0.01). Despite concern that anti-progestogenic effects may jeopardize contraception, there were no pregnancies. This approach may offer a useful strategy to improve continuation rates by alleviating unwanted side-effects until bleeding patterns improve spontaneously with time.", "nan", "Evaluate the efficacy of tranexamic acid and placebo for controlling irregular uterine bleeding in depot-medroxyprogesterone acetate (DMPA) users.\n A double-blind, placebo-controlled study was conducted on 100 DMPA users attending the Family Planning Clinic King Chulalongkorn Memorial Hospital. All users had abnormal bleeding. They were randomly divided in two groups; a group of 50 received tranexamic acid, 250 mg four times a day for 5 days and another group of 49 received placebo in the same manner. One subject dropped out from the study. Total day of bleeding/spotting and percentage of women in whom bleeding was stopped were analyzed at the end of weeks 1 and 4.\n The percentage of subjects in whom bleeding was stopped during the first week after initial treatment was significantly higher in the tranexamic acid group than the placebo group (88% vs. 8.2%, p < 0.001). During the follow-up period (4 weeks after initial treatment), a bleeding-free interval of > 20 days was found in 68% of subjects treated with tranexamic acid and 0% treated with placebo(p < 0.001). The mean number of bleeding/spotting days were also significantly different between the groups (5.7 +/- 2.5 vs. 17.5 +/- 7.2 days, p < 0.05).\n Tranexamic acid was more effective than placebo in short-term treatment of irregular uterine bleeding/spotting associated with DMPA use.", "The most common side-effect and reason for discontinuation with Norplant use is bleeding disturbance. The aim of this study was to investigate whether the 6 week application of a patch which released 100 micrograms/day oestradiol would reduce the number of abnormal bleeding days or eliminate the problem. Another objective was to find out the correlation between the bleeding pattern and endometrial concentrations of oestrogen receptor (ER) and progesterone receptor (PR). Of 98 Norplant users, 34 patients had normal bleeding patterns and 64 patients had abnormal bleeding patterns. An oestradiol patch or a placebo patch were randomly used to treat 33 and 31 women with abnormal bleeding respectively. There was a clinical improvement in the oestradiol group compared with the placebo group, although this was not statistically significant. There were no correlations between PR and ER concentration and the serum oestradiol, progesterone, levonorgestrel and sex hormone-binding globulin concentrations. Significantly increased mean immunostaining scores of stromal PR were observed in those Norplant users whose endometrium had an atrophic histological appearance. The serum oestradiol concentration did not show a significant change after treatment with the oestradiol patch compared with the placebo patch.", "The aim of this double-blind, placebo-controlled study was to evaluate the effect of mefenamic acid and placebo on controlling irregular uterine bleeding secondary to Norplant use. A total of 67 Norplant users attending the Family Planning Clinic of Chulalongkorn Hospital all had irregular bleeding. These women were randomly allocated into two groups. A total 34 users received mefenamic acid, 500 mg twice a day for 5 days, and placebos were given to the other 33 in the same manner. The total days of bleeding and spotting and the percentage of women in whom bleeding was stopped were analyzed in weeks 1 and 4. The percentage of subjects in whom bleeding was stopped during week 1 after initial treatment was significantly higher in the mefenamic acid group than the placebo group (76%, 27%; p < 0.001). In the follow-up period (4 weeks after initial treatment), a bleeding-free interval of > 20 days was found in 68% of the subjects treated with mefenamic acid and 33% treated with the placebo; the mean number of bleeding/spotting days was lower with mefenamic acid treatment (11.6 and 17.2 days; p < 0.05). The difference was statistically significant. It is concluded that mefenamic acid was more effective than placebo in short-term control of irregular bleeding and spotting associated with Norplant use.", "The safety and efficacy of the anti-progestogen Org 31710 in improving cycle control in healthy women using the desogestrel progestogen-only pill was investigated in this randomized, double-blind, placebo-controlled study.\n A total of 103 women using the 75 micro g desogestrel progestogen-only pill daily also received either 150 mg Org 31710 or placebo once every 28 days, starting on day 1, for a duration of 4-7 treatment cycles.\n The percentage of women with bleeding or spotting (B/S) every day in the placebo group was on average 30% during the whole treatment period and no days without reported B/S occurred. In contrast, a cyclic pattern was observed for the Org 31710 group; a peak incidence of B/S was observed on day 3 or 4 of each cycle, followed by a sharp decrease on cycle days 9-15. Compared with controls, less subjects in the Org 31710 group reported irregular, frequent or prolonged bleeding. These differences were clearly observed in the initial cycles, but were somewhat less pronounced during the later cycles of the treatment period. A relatively high incidence of B/S episodes starting in the second section of the cycle was also observed.\n The addition of Org 31710 once a month improved cycle control in women using daily treatment with 75 micro g desogestrel.", "Norplant subcutaneous implantation is a contraceptive method used in Indonesia. Endometrial bleeding is one major reason to discontinue the use of Norplant. Angiogenic response in the endometrium of Norplant users was found to be lower than in women with normal menstrual cycle. This disturbance in the angiogenic process may be caused by an imbalance of pro- and antioxidant processes in the endometrium of Norplant users. The aim of this study is to investigate the effect of vitamin E on the endometrial angiogenic activity and to assess the efficacy of vitamin E supplementation in treating endometrial bleeding in Norplant users. Subjects for this study were selected from Norplant users with an exposure of at least 3 months, with endometrial bleeding and recruited on the basis of fully informed consent. TBA reaction was used to measure degradation products of lipid peroxidation. The endometrial angiogenic response was assayed according to Folkman et al. (Folkman et al., 1989. Nature 239, 58-61). Samples from endometrial biopsies were incubated in vitro with vitamin E or placebo before angiogenic measurement. For in vivo supplementation, vitamin E 200 mg/day, or placebo for 10 days/month were given to the subjects with double blind randomisation. The results showed that the blood levels of TBA-reactive substances were significantly higher in Norplant users than in controls. In the endometrium from Norplant users with bleeding problems, in vitro supplementation of vitamin E resulted in a significantly higher angiogenic score than placebo. Although a highly significant reduction of bleeding days in both groups, vitamin E and placebo, was seen during the 2 months of the study, the number of bleeding days was significantly lower in women treated with vitamin E than with placebo.", "The effectiveness of three drugs in controlling prolonged bleeding in the first year of NORPLANT implants use was tested. The drugs were levonorgestrel (L-Ng, 0.03 mg twice a day for 20 days), ethinylestradiol (EE, 0.05 mg per day for 20 days) and ibuprofen (Ib, 800 mg three times a day for 5 days) and were given orally. A control group received a placebo (PL, one pill of lactose for 20 days). Treatment should start each time a woman experienced eight consecutive days of bleeding or spotting. The 183 volunteers were not aware of the drug administered. A daily record of bleeding and spotting and of treatment intake was maintained. One-hundred-forty women completed the study period; 60 never used the prescribed treatment. Women treated with the three test drugs had significantly fewer bleeding and spotting days during the treated month and also throughout the study year than women using the placebo. The mean number of bleeding plus spotting days per actually treated subject in the first year was 77, 94, 101 and 129 days for the EE, Ib, L-Ng and PL groups, respectively. The administration of EE might help in the management of prolonged bleeding during the first year of NORPLANT implants use.", "Irregular menstrual bleeding is a common reason for discontinuation of depot medroyprogesterone acetate (DMPA) contraception. We conducted a double-blind, randomized placebo controlled trial to estimate if transdermal estradiol used in a cyclic fashion could make DMPA bleeding patterns more acceptable and improve DMPA continuation rates. Women initiating DMPA contraception immediately post-abortion (N = 132) were randomized to receive either a low sustained dose of transdermal 17-beta estradiol (0.10 mg/day, Climara) or an identical placebo to be used in a cyclic manner for 3 months. Bleeding patterns, contraceptive use, and pregnancy rates were measured for 1 year after enrollment. Cyclic transdermal estrogen did not create regular bleeding patterns in new users of DMPA and had no effect on DMPA continuation rates (relative hazard = 0.93, 95%CI 0.65-1.33). By 12 months after enrollment, 19.4% of those randomized to estrogen and 23.9% of those randomized to placebo were still using DMPA for contraception. There was no difference in the frequency of DMPA discontinuation primarily for abnormal uterine bleeding between groups (relative risk ratio = 0.95, 95%CI 0.40-2.23). Few women who discontinued DMPA switched to highly effective methods of contraception and within 1 year of an abortion, there were 18 repeat pregnancies (21.9%). Compliance with the estrogen patches was poor resulting in early study termination and inadequate statistical power to detect a clinically significant difference in DMPA continuation rates. Continuation rates of DMPA were low and repeat pregnancy rates were high among women initiating DMPA at the time of abortion. Cyclic transdermal estradiol use is an unacceptable regimen for preventing the irregular bleeding associated with DMPA initiation.", "A clinical study was conducted to assess the effects of oestrogen in controlling increased endometrial bleeding problems in the first year of Norplant use. Three treatment groups were studied: (i) 50 micrograms ethinyl oestradiol (EE); (ii) a combined pill containing 30 micrograms EE and 150 micrograms levonorgestrel (LNG); and (iii) placebo. Based on menstrual diary records, women with prolonged, frequent or irregular bleeding, as defined by World Health Organization criteria, were randomly allocated to one treatment for 21 days. A first endometrial biopsy was taken before commencing treatment and a second biopsy at either day 14 or 21 of treatment. Following treatment, all subjects kept a menstrual diary card for 90 days. In this preliminary study, 48 subjects had completed the full 90 day post-treatment record. Within 21 days of EE treatment, the number of bleeding/spotting days was reduced significantly (P < 0.02). In the 90 days following treatment, the administration of EE and EE + LNG significantly decreased the number of bleeding/spotting days (P < 0.05). There was no reduction in the number of bleeding/spotting episodes in the EE and EE + LNG groups, but the length of each bleeding/spotting episode was significantly shorter (P < 0.05). Histopathological findings of endometrium on day 0 revealed consistent progestogenic effects, and there was no apparent change in response by day 14 or 21 of EE or EE + LNG treatment. The results of this study confirm the clinical effectiveness of EE and EE + LNG for the treatment of irregular, frequent and prolonged bleeding in Norplant users.", "nan", "Increased matrix metalloproteinase (MMP) activity in the endometrium is a predisposing factor for bleeding with depot medroxy progesterone acetate (DMPA) injectable contraception. Doxycycline (DOX) has been proven in vitro to inhibit MMP-mediated degradation of stromal matrix. The current study examined the effect of DOX compared to placebo in treating a current bleeding episode during DMPA use.\n A double-blinded randomized controlled trial was conducted in Assiut, Egypt. DMPA users with current bleeding episode were counseled to participate. Women who agreed to participate were randomly assigned to receive 100 mg DOX twice daily for 5 days (34 patients) or an identical placebo (34 patients). All participants were asked to report bleeding and spotting days in a menstrual diary. All participants were followed for 3 months after treatment. This trial was registered (NCT01254799).\n The relative risk to stop a bleeding episode within 10 days of starting treatment was 0.88 (confidence interval 0.64-1.21) in the treatment group compared to the control. DOX treatment caused no significant difference compared to placebo in the number of bleeding and/or spotting days in the 3 months following the treatment.\n Doxycycline as MMP inhibitor is not effective in stopping a current attack of bleeding with DMPA. It also does not improve the bleeding characteristics of women for the subsequent 3 months following the treatment.\n Copyright © 2012 Elsevier Inc. All rights reserved.", "The major side-effect of progestogen-only contraception is disruption of menstrual bleeding patterns, which can lead to a high incidence of early discontinuation. The aim of this study was to compare three treatments with placebo on the duration and recurrence of frequent and/or prolonged bleeding in Implanon users.\n Women between the ages of 18 and 45 years, who had used Implanon for > or =3 months and were experiencing prolonged or frequent bleeding patterns, were recruited at four Australian sites. Subjects were randomized to treatment using computer-generated random number table if they met the World Health Organization criteria for prolonged and/or frequent bleeding in the previous 90 days [Belsey, E.M., Pinol, A.P.Y. and Taskforce on Long-Acting Systemic Agents for Fertility Regulation, World Health Organization (1997) Contraception 55,57-65]. Treatments were: (1) mifepristone 25 mg given twice on day 1 followed by 4 days of twice daily placebo; (2) mifepristone 25 mg given twice on day 1 followed by 4 days of ethinyl estradiol (EE) 20 microg in the morning and placebo at night; (3) doxycycline 100 mg twice daily for 5 days; and (4) placebo twice daily for 5 days. Analysis was by intention to treat. The primary endpoint was the number of days of bleeding and spotting immediately following initiation of the 5 day course of each active therapy compared with placebo.\n A total of 179 women was assigned to treatment. Both mifepristone in combination with EE and doxycycline alone were significantly more effective in stopping an episode of bleeding {mean 4. 3 days [confidence interval (CI) 3.5-5.2], and 4.8 days (CI 3.9-5.8) respectively} than mifepristone alone or placebo [5.9 days (CI 4.8-7.2) and 7.5 days (CI 6.1-9.1) respectively]. No effect on subsequent bleeding patterns was observed in any treatment group.\n Both mifepristone plus EE and doxycycline alone were significantly more effective than placebo in terminating an episode of bleeding in women with prolonged and/or frequent bleeding using Implanon. We believe that the observed reduction in the number of bleeding days by almost 50% compared to placebo in both the mifepristone combination group and the doxycycline group demonstrates a clinically significant improvement in bleeding patterns and that further trials are needed to compare different combinations of therapy as well as multiple dosing regimens in order to establish which is the most effective treatment option. The effect of repeat administration or combinations of these preparations on long-term bleeding patterns requires further investigation.", "Pilot data have indicated that both doxycycline alone and mifepristone combined with ethinyl estradiol (EE) are effective in stopping episodes of bleeding in Implanon users with troublesome bleeding. We compared four treatments against a placebo in Implanon users and tested whether repeated treatment improved subsequent bleeding patterns.\n Implanon users aged 18-45 years were randomized to treatment with (i) mifepristone 25 mg given twice on day 1 followed by 4 days of EE 20 microg; (ii) doxycycline 100 mg twice daily for 5 days; (iii) mifepristone 25 mg given twice on day 1 plus doxycycline 100 mg twice daily for 5 days; (iv) doxycycline 100 mg twice daily with EE 20 microg daily; and (v) placebo twice daily for 5 days. The primary end-point was the number of days of bleeding/spotting immediately following initiation of the first 5-day course of each therapy, compared with placebo.\n There were 204 women assigned to treatment. Mifepristone in combination with either EE or doxycycline was significantly more effective in stopping an episode of bleeding (mean 4.0 days (CI 3.5-4.6) and 4.4 days (CI 3.8-5.2), respectively) than doxycycline alone or in combination with EE, or placebo (6.4 days (CI 4.4-9.2), 6.4 days (CI 4.8-8.6) and 6.4 days (CL 5.1-8.0), respectively).\n Mifepristone combined with either EE or doxycycline was significantly more effective than placebo in terminating an episode of bleeding in Implanon users. However there was no improvement in subsequent bleeding patterns. Trial registration number: ACTR # 012605000206628.", "The purpose of this study is to evaluate the effects of tranexamic acid and placebo on controlling irregular uterine bleeding secondary to Norplant use.\n A prospective randomized, double-blind, placebo-controlled trial was conducted. Sixty-eight Norplant users who had irregular bleeding were randomly allocated into two groups. A total of 34 users received tranexamic acid 500 mg twice a day for 5 days; the placebo was given to the other 34 users in the same manner. The total number of days of bleeding and spotting and the percentage of women whose irregular uterine bleeding was stopped was analyzed at the end of weeks 1 and 4.\n In the follow-up period (4 weeks after the initial treatment), a bleeding-free interval of > 20 days was found in 58.8% of the subjects treated with tranexamic acid and in 76.5% treated with placebo (p = .12). The percentage of subjects whose irregular uterine bleeding stopped during week 1 after the initial treatment was significantly higher in the tranexamic acid group than those in the placebo group (64.7% vs. 35.3%, p = .015). The mean number of bleeding/spotting days was not significantly different between the groups (15.4 vs. 12.7 days, p = .182).\n Tranexamic acid for 5 days appears to be an effective treatment for irregular uterine bleeding associated with Norplant use only while it is being used. However, treatment for 5 days does not seem to provide long-term benefit.", "The objective of this double-blind, placebo-controlled study was to evaluate the effect of mefenamic acid and placebo on controlling irregular uterine bleeding in depot-medroxyprogesterone acetate (DMPA) users. A total of 48 DMPA users attending the Family Planning Clinic, Chulalongkorn Hospital were studied, all had abnormal bleeding. These participants were randomly divided into two groups. A total of 23 users received mefenamic acid, 500 mg, twice a day for 5 days, and placebos were given to the other 25 in the same manner. Total days of bleeding and spotting and percentage of women in whom bleeding was stopped were analyzed in the first and the fourth week. Percentage of subjects in whom bleeding was stopped during the first week after initial treatment was significantly higher in the mefenamic acid group than the placebo group (69.6%, 40.0%; p < 0.05). During the follow-up period (4 weeks after initial treatment), the mean of the bleeding-free interval during 28 days was found to be 16.1 days in the subjects treated with mefenamic acid and 12.39 days in the placebo group. However, the difference was not statistically significant. From the results of the study, we concluded that mefenamic acid was effective in very short-term control of bleeding during DMPA use, but not effective long-term.\n Copyright 2004 Elsevier Inc.", "nan", "Depo-medroxyprogesterone acetate (DMPA) is an effective injectable contraceptive with worldwide availability. However, it is associated with a high incidence of breakthrough bleeding (BTB) during the first 6 months of use which often leads to discontinuation. Mifepristone is a progesterone receptor antagonist that has been demonstrated to decrease BTB caused by the levonorgestrel subdermal implant (Norplant). The purpose of this study was to determine if mifepristone would decrease BTB in new starters of DMPA. Twenty regularly cycling women who were new starters of DMPA were randomized to receive 50 mg of mifepristone or placebo every 2 weeks for 24 weeks. Percent days of BTB and number of cycles with bleeding intervals > or =8 and > or =14 days were evaluated using daily bleeding diaries. Ovulation was determined by measuring thrice-weekly urinary metabolites of estrogen and progesterone. Endometrial concentrations of ER and PR were determined by immunohistochemistry. Mifepristone significantly decreased the percent days of BTB and the number of cycles with prolonged bleeding intervals when compared to placebo. No subject ovulated in either group. ER immunostaining increased and PR immunostaining decreased after mifepristone treatment. In conclusion, a 50 mg dose of mifepristone taken every 2 weeks decreases the incidence of BTB in new starters of DMPA. This effect may be due to modulation of endometrial estrogen and progesterone receptors.", "The aim of this double-blind, placebo-controlled study was to evaluate the effect of mefenamic acid and placebo on controlling irregular uterine bleeding secondary to Implanon use.\n Randomized placebo controlled trial.\n Family Planning Clinic, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.\n A total number of 50 Implanon users with irregular bleeding who attended the Family Planning Clinic at Chulalongkorn Memorial Hospital. These subjects were randomly allocated into two groups. Twenty-five users received mefenamic acid, 500 mg per oral three times a day for 5 days, and placebos were given to the rest of studied subjects in the similar manner. During the follow-up periods, the participants were requested to maintain their daily record of bleeding, spotting, and adverse effects. The days of bleeding and spotting and the percentage of bleeding stopped women were analyzed in week 1 and 4.\n The percentage of subjects in whom bleeding was stopped during week 1 after initial treatment was significantly higher in the mefenamic acid group than that of the placebo group (65.20%, 21.70%; p < 0.05). During the follow-up period (4 weeks after initial treatment), a bleeding free-interval of > 20 days was found in 56.50% of the subjects treated with mefenamic acid and 21.70% of those treated with placebo; The mean number of bleeding/spotting days was lower in the group of patients with mefenamic acid treatment (10.52 and 16.78 days; p < 0.05). The difference is statistically significant.\n Mefenamic acid was more effective than placebo in short-term treatment of irregular bleeding and spotting associated with Implanon use.", "The study was conducted to evaluate ethinyl estradiol (EE) or ibuprofen (IBU) compared to placebo (PL) on spotting and bleeding (S/B) and a postcoital test (PCT) in women using the levonorgestrel subcutaneous implant. Women experiencing excessive S/B were enrolled in a multicenter prospective randomized study using EE, IBU or PL.\n Duration of S/B and a PCT were evaluated. Statistical analysis used a general linear model procedure with Duncan's multiple range tests for individual variables.\n One hundred seven women were evaluated, and there was no difference in the duration of bleeding among the three therapies, while the mean number of spotting days were 1.8 for EE and 2.8 for PL (p=.04). There was no effect of IBU on S/B. No effect on cervical mucus or sperm was found between treatments.\n There was a decrease in spotting but no effect on bleeding with EE compared to PL." ]

[ "12010667", "9213829", "14671696", "15946202", "12885680", "8024227", "11775653", "20860504", "22487001", "11775651", "1291926", "2678804", "8810655", "329257", "15678251", "4922059", "22108471", "22360152", "19299272", "2098372", "10431991" ]

[ "High versus low doses of unfractionated heparin for the treatment of superficial thrombophlebitis of the leg. A prospective, controlled, randomized study.", "[Effectiveness and tolerability of heparan sulfate in the treatment of superficial thrombophlebitis. Controlled clinical study vs sulodexide].", "Low-molecular-weight heparin versus saphenofemoral disconnection for the treatment of above-knee greater saphenous thrombophlebitis: a prospective study.", "High vs. low doses of low-molecular-weight heparin for the treatment of superficial vein thrombosis of the legs: a double-blind, randomized trial.", "A pilot randomized double-blind comparison of a low-molecular-weight heparin, a nonsteroidal anti-inflammatory agent, and placebo in the treatment of superficial vein thrombosis.", "[Therapeutic management of superficial venous thrombosis with calcium nadroparin. Dosage testing and comparison with a non-steroidal anti-inflammatory agent].", "Treatment of superficial vein thrombosis: clinical evaluation of Essaven gel--a placebo-controlled, 8-week, randomized study.", "Fondaparinux for the treatment of superficial-vein thrombosis in the legs.", "A randomized double-blind study of low-molecular-weight heparin (parnaparin) for superficial vein thrombosis: STEFLUX (Superficial ThromboEmbolism and Fluxum).", "Treatment of superficial vein thrombosis with standardized application of Essaven gel--a placebo-controlled, randomized study.", "[Clinical study of the therapeutic efficacy and tolerance of nimesulide in comparison with a sodium diclofenac in the treatment of acute superficial thrombophlebitis].", "Treatment of acute superficial thrombosis and follow-up by computerized thermography.", "Tolerability and clinical efficacy of desmin in the treatment of superficial thrombovaricophlebitis.", "Comparison of oxyphenbutazone and placebo in the treatment of superficial thrombophelbitis: an object lesson in clinical trial design.", "Liposomal heparin spray: a new formula in adjunctive treatment of superficial venous thrombosis.", "Indomethacin in superficial thrombophlebitis.", "Topical formulation of heparin is effective in reducing the symptoms of superficial venous thrombosis: a monocenter, observer-blind, placebo-controlled randomized study.", "A randomized trial of dalteparin compared with ibuprofen for the treatment of superficial thrombophlebitis.", "A comparison of low-molecular-weight heparin and combined therapy of low-molecular-weight heparin with an anti-inflammatory agent in the treatment of superficial vein thrombosis.", "Evolution of superficial vein thrombosis treated with defibrotide: comparison with low dose subcutaneous heparin.", "Superficial thrombophlebitis of the legs: a randomized, controlled, follow-up study." ]

[ "The optimal treatment of superficial thrombophlebitis of the leg is undefined. The main study objective was to assess the efficacy and safety of unmonitored high doses as compared to low doses of unfractionated heparin (UFH) for prevention of venous thromboembolic complications in patients with superficial thrombophlebitis of the thigh.\n Sixty consecutive patients with acute thrombophlebitis of the great saphenous vein, as assessed by ultrasonography, were randomized to subcutaneous injection twice daily of UFH in high unmonitored doses (12,500 IU for one week followed by 10,000 IU) or prophylactic doses (5,000 IU) for four weeks. The rate of asymptomatic involvement of the deep venous system and/or symptomatic thromboembolic events during a six-month follow-up period was assessed and compared between the two study groups.\n Six of the 30 patients (20.0 %; 95% CI, 7.7 to 38.6) randomized to low-dose UFH developed symptomatic or asymptomatic events as compared to 1 of the 30 patients (3.3%; 95% CI, 0.07 to 17.2) who received high-dose UFH (p=0.05 by one-sided Fisher's exact test). No patient experienced major bleeding complications in either group.\n The results of this study suggest that in patients with acute thrombophlebitis of the thigh unmonitored high doses of UFH are more effective than prophylactic doses of UFH for prevention of venous thromboembolic complications and do not enhance the risk of bleeding complications.", "One of the most interesting glycosaminoglycans (GAGs) is heparansulphate, known as the physiological activator of antithrombin III and involved in the maintenance of the antithrombotic potential of uninjured endothelium. The aim of our study was to evaluate the tolerability and effectiveness of heparansulphate with respect to sulodexide, another GAG suitable for the treatment of venous diseases. The study was performed in a open-label, controlled, with parallel and randomized groups, design. Thirty patients (aged 32-72 years) suffering from superficial thrombophlebitis were treated for two weeks with heparansulphate 100 mg t.i.d. or sulodexide 250 LSU b.i.d., both given orally. Some coagulative and fibrinolytic parameters (PT; aPTT; fibrinogen; euglobulin lysis time; t-PA; PAI-1; ATIII; alpha 2-antiplasmin; D-Dimer and platelets count) were assayed at the beginning and at the end of the study. Moreover signs and symptoms of disease (skin trophism; local pain; itch and oedema) were assessed. Heparansulphate and sulodexide were able to reduce signs and symptoms with similar degree and to significantly modify t-PA, alpha 2-antiplasmin and ATIII levels without any difference between treatments. Our issues show that heparansulphate can be useful in superficial thrombophlebitis management.", "The objective of this study was to assess the efficacy, safety, and cost of low-molecular-weight heparin compared to saphenofemoral disconnection for the treatment of internal saphenous proximal thrombophlebitis (SPT). Eighty-four consecutive patients diagnosed as presenting SPT alone (symptoms/echo-Doppler) were divided into 2 comparable groups treated with (1) saphenofemoral disconnection under local anesthesia with a short hospital stay (n = 45) or (2) prospective enoxaparin on an outpatient basis for 4 weeks (n = 39). Informed consent was obtained and inclusion, exclusion, and withdrawal criteria were established. Patients were followed up at 1, 3, and 6 months. Thirty patients per group completed the study requirements. In the disconnection group, 2 patients (6.7%) presented complications of the surgical wound, 1 (3.3%) had SPT recurrence (however, there was no deep venous thrombosis), and 2 (6.7%) had nonfatal pulmonary embolism confirmed by radionuclide scan. In the enoxaparin group, there were 2 cases (6.7%) of minor bleeding (epistaxis and rectal bleeding) and 3 (10%) recurrences of SPT. In the enoxaparin group there was no case of progression of the thrombosis to the deep venous system or pulmonary embolism. The study found no statistically significant differences between saphenofemoral disconnection and enoxaparin in the treatment of SPT, but the low-molecular-weight heparin group had socioeconomic advantages.", "In contrast with extensive information on the management of deep vein thrombosis of the lower extremities, little is known on the most appropriate treatment of the superficial vein thrombosis (SVT). In a multicenter, prospective, controlled, double-blind, double-dummy clinical trial, 164 consecutive patients with acute SVT of the great saphenous vein were randomized to receive the s.c. administration of either fixed prophylactic doses (2850 a-Xa IU) or body-weight adjusted therapeutic doses of nadroparin once daily for 1 month. The main study outcome was to compare the rate of asymptomatic and symptomatic extension of SVT and/or venous thromboembolic (VTE) complications during a 3-month follow-up period. Of the 81 patients randomized to the prophylactic doses, seven [8.6%; 95% confidence interval (CI), 3.5-17.0] developed SVT progression or VTE complications as compared with six of the 83 (7.2%; 95% CI, 2.8-15.1) allocated to the treatment group (absolute difference, 1.4; 96% CI, -6.9 to 9.7; P = 0.74). No patient in either group developed major bleeding. Our findings suggest that therapeutic doses of low-molecular-weight heparin, administered for 1 month in patients with SVT of the greater saphenous vein do not improve results obtained by prophylactic doses, administered for the same period, over a 3-month follow-up period.", "The efficacy and safety of antithrombotic treatment in patients with superficial vein thrombosis remain to be established in adequately designed trials.\n In a double-blind trial, 427 patients older than 18 years, with documented acute symptomatic superficial vein thrombosis of the legs, were randomly assigned to receive subcutaneous enoxaparin sodium, 40 mg; subcutaneous enoxaparin, 1.5 mg/kg; oral tenoxicam; or placebo, once daily for 8 to 12 days. The primary efficacy outcome was deep venous thromboembolism between days 1 and 12, defined as deep vein thrombosis detected by ultrasonography between days 8 and 12 or earlier if clinically indicated, or documented symptomatic pulmonary embolism. For the secondary efficacy outcomes, superficial vein thrombosis recurrence or extension was also considered.\n The incidence of deep venous thromboembolism by day 12 was 3.6% (4 of 111 patients) in the placebo group, 0.9% (1 of 109 patients) in the 40-mg enoxaparin group (P =.37 vs placebo), 1.0% (1 of 102 patients) in the 1.5-mg/kg enoxaparin group (P =.37 vs placebo), and 2.1% (2 of 94 patients) in the tenoxicam group (P =.69 vs placebo). The incidence of deep and superficial venous thromboembolism by day 12 was significantly reduced in all active treatment groups, from 30.6% (34 of 111 patients) in the placebo group to 8.3% (9 of 109 patients), 6.9% (7 of 102 patients), and 14.9% (14 of 94 patients) in the 40-mg enoxaparin (P<.001), 1.5-mg/kg enoxaparin (P<.001), and tenoxicam (P<.01) groups, respectively. No death or major hemorrhage occurred during the study.\n Treatment with a low-molecular-weight heparin or with an oral nonsteroidal anti-inflammatory agent should be evaluated further in the prevention of thromboembolic complications in patients with superficial vein thrombosis.", "This multicentre, randomised, open trial compared the efficacy and safety/acceptability of calcium nadroparin, a non-steroidal anti-inflammatory drug, naproxen, in the treatment of superficial venous thrombosis of the lower limbs, in 117 patients. Calcium nadroparin was given at two dosage regimens: a fixed dose (daily subcutaneous injection of 0.6 ml, i.e. 6150 anti-Xa IU, n = 38) or a dose adjusted for body weight (31.5 anti-Xa IU/kg, n = 40). The naproxen was given orally (500 mg as a single daily dose, n = 39). Treatment duration was 6 days in both groups. A very marked difference was found to the advantage of calcium nadroparin, although this difference did not reach the threshold of statistical significance with regard to repermeabilisation of the thrombosed superficial vein at the end of treatment. The most striking result concerned the regression of symptoms and signs. At the end of treatment (D7), there was a significant difference to the advantage of the calcium nadroparin groups, particularly regarding feelings of heat and redness (p < 0.001 in both cases). The persistence of symptoms and signs at 8 weeks was statistically less frequent (p = 0.007) in the calcium nadroparin groups than in the naproxen group. Efficacy did not differ between the calcium nadroparin fixed dose and calcium nadroparin weight-adjusted dose groups. No adverse events nor clinically significant laboratory abnormalities were encountered. Antithrombotic treatment of superficial venous thromboses with calcium nadroparin is well tolerated and appears to be associated with a greater improvement in symptoms and signs, in the short and mid-terms, than that obtained with an oral non-steroidal anti-inflammatory.", "The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG), in comparison with placebo in 30 patients with superficial vein thrombosis (SVT). The 8-week study evaluated SVT with an analogue clinical/symptomatic score. SVT was associated with varicose veins. In patients treated with active EG the decrease in score was significantly larger (p< 0.02) than in the placebo group. No intolerance was observed. The decrease in score in the placebo group was due to spontaneous resolution and to skin manipulation and massage. In conclusion local treatment with EG in SVT improves signs/symptoms much faster than placebo. This study confirms earlier observation on the effective, local use of EG in SVT.", "The efficacy and safety of anticoagulant treatment for patients with acute, symptomatic superficial-vein thrombosis in the legs, but without concomitant deep-vein thrombosis or symptomatic pulmonary embolism at presentation, have not been established.\n In a randomized, double-blind trial, we assigned 3002 patients to receive either fondaparinux, administered subcutaneously at a dose of 2.5 mg once daily, or placebo for 45 days. The primary efficacy outcome was a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep-vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of superficial-vein thrombosis at day 47. The main safety outcome was major bleeding. The patients were followed until day 77.\n The primary efficacy outcome occurred in 13 of 1502 patients (0.9%) in the fondaparinux group and 88 of 1500 patients (5.9%) in the placebo group (relative risk reduction with fondaparinux, 85%; 95% confidence interval [CI], 74 to 92; P<0.001). The incidence of each component of the primary efficacy outcome was significantly reduced in the fondaparinux group as compared with the placebo group, except for the outcome of death (0.1% in both groups). The rate of pulmonary embolism or deep-vein thrombosis was 85% lower in the fondaparinux group than in the placebo group (0.2% vs. 1.3%; 95% CI, 50 to 95; P<0.001). Similar risk reductions were observed at day 77. A total of 88 patients would need to be treated to prevent one instance of pulmonary embolism or deep-vein thrombosis. Major bleeding occurred in one patient in each group. The incidence of serious adverse events was 0.7% with fondaparinux and 1.1% with placebo.\n Fondaparinux at a dose of 2.5 mg once a day for 45 days was effective in the treatment of patients with acute, symptomatic superficial-vein thrombosis of the legs and did not have serious side effects. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00443053.)", "Optimal doses and duration of low-molecular-weight heparin (LMWH) for the treatment of superficial vein thrombosis (SVT) are still uncertain.\n To compare the efficacy and safety of different doses and durations of LMWH parnaparin for symptomatic lower limb SVT.\n Outpatients with at least a 4-cm-long SVT of long or short saphenous veins or their collaterals were randomized to receive parnaparin either 8500 UI once daily ( o.d.) for 10 days followed by placebo for 20 days (group A) or 8500 UI o.d. for 10 days followed by 6400 UI once daily (o.d.) for 20 days (group B) or 4250 UI o.d. for 30 days (group C) in a double-blind fashion in 16 clinics. Primary outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT), symptomatic pulmonary embolism (PE) and relapse and/or symptomatic or asymptomatic SVT recurrence in the first 33 days with 60 days follow-up.\n Among 664 patients, primary outcome occurred in 33/212 (15.6%), 4/219 (1.8%) and 16/217 (7.3%) subjects in groups A, B and C, respectively (B vs. A: absolute risk reduction [ARR]: 13.7%, 95% confidence intervals [CI]: 8-18.9 P<0.001; B vs. C: ARR: 5.5%; 95% CI: 1.6-9.4 P= 0.011; C vs. A: ARR: 8.2%, 95% CI: 2-14 P=0.012). During days 0-93, the event rate was higher in group A (22.6%) than either in group B (8.7%; P=0.001) or C (14.3%, P=0.034). No major hemorrhages occurred.\n An intermediate dose of parnaparin for 30 days is superior to either a 30-day prophylactic dose or a 10-day intermediate dose for lower limb SVT treatment.\n © 2012 International Society on Thrombosis and Haemostasis.", "The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) in comparison with placebo in 30 patients with superficial vein thrombosis (SVT). The 4-week study evaluated the average skin temperature and an analogue symptomatic score. Below-knee SVT was associated with large varicose veins. In patients treated with active EG the decrease in score and in the average, composite skin temperature was significantly larger than in the placebo and control groups. No intolerance was observed. The decrease in score and temperature in the placebo group was mainly due to skin manipulation and massage. In conclusion, treatment with EG in SVT improves symptoms and decreases skin temperature faster. This study confirms earlier observations on the effective use of EG in SVT.", "The efficacy and tolerability of nimesulide were assessed in a randomized study versus diclofenac sodium in the treatment of 50 patients affected with acute superficial thrombophlebitis. Both drugs, administered in a dose of 1 tablet b.i.d. for 10 days, evidenced a prompt and effective analgesic and anti-inflammatory activity. Particularly, the tolerability of nimesulide was excellent.", "Superficial vein thrombosis (SVT) is a common complication of varicose veins. Treatment may be surgical by removal of the superficial clots under local anesthetic or medical in association with elastic compression and mobilization. In this study 83 patients with SVT were randomised in treatments groups: A--superficial thrombectomy and elastic compression (EC); B--Ca Heparin (0.5 mgs b.i.b.) + EC; C--Venoruton (1 g, t.i.d.) + EC; D--Venoruton (1 g, t.i.d.) after superficial thrombectomy + EC; E--elastic compression. All treatments were applied for 8 weeks. The evolution of SVT was studied by a system, based on thermography, which analyse by a computerized system the variation of the hyperthermic areas (HA) on thermograms. This was associated with subjective and objective clinical evaluation. Results indicate a decrease of HA in all groups but patients treated with superficial thrombectomy show a significantly (p, 0.05) greater and faster reduction of HA. The reduction of HA produced by Venoruton was also significantly greater (p less than 0.05) than that observed in patients treated by Ca Heparin or elastic compression and it determined also a faster and greater (p less than 0.05) decrease of HA after thrombectomy. These results were confirmed by clinical observations. In conclusion results from this study indicate a positive effect of Venoruton in SVT in determining a faster decrease of hyperthermic areas probably by decreasing local inflammation.", "Fifty-six patients with superficial thrombovaricophlebitis of the lower limbs were enrolled in an open and multicenter (4 centers) trial for a period of thirty days. Patients were randomly allocated to three treatment groups to receive a new low-molecular-weight dermatan sulfate (Desmin) at the dose, respectively, of 100 mg once daily by subcutaneous (SC) route, 100 mg twice a day SC, and 200 mg once daily by intramuscular (IM) route. The general and local tolerability and the clinical efficacy of the drug were evaluated by means of clinical, instrumental, and laboratory parameters. Desmin proved capable of effectively improving the symptoms of patients affected by thrombovaricophlebitis, inducing rapid regression by the tenth day of treatment. The daily dose of 200 mg (either SC or IM) was more effective than the 100 mg dose. The systemic tolerability of the drug, administered for the first time for one month, was extremely good, without significant variations in the relevant laboratory tests. Local tolerance (at the site of injection) of the drug was also good.", "nan", "The objective of this study was to assess the efficacy and safety of liposomal heparin spray-a new formula of topical heparin delivery. This was a randomized, multicenter, controlled open clinical trial with 2 parallel groups. Forty-six outpatients with clinical signs of superficial venous thrombosis (SVT) were treated with either topical liposomal heparin spraygel (LHSG) (Lipohep Forte Spraygel, 4 puffs of 458 IU tid (n = 22) or with low-molecular-weight heparin (LMWH) (Clexane 40 mg once a day (n = 24), administered subcutaneously (sc). Main outcome measures were efficacy parameters (improvement of local symptoms-pain control and planimetric evaluation of erythema size, duplex Doppler assessment of thrombus regression) and safety parameters (documentation of adverse events, with particular reference to deep vein thrombosis [DVT] by duplex sonography, and patients' and investigators' assessment of drug tolerance). Patients' and investigators' subjective assessment of efficacy of treatment and change in basic biochemical parameters were defined as secondary outcome measures. Statistical analysis was performed with use of Wilcoxon test, Mann-Whitney U-test and Chi-square test. Regression of SVT-related symptoms, including pain, erythema, and thrombus presence, was shown as comparable in LHSG and LMWH groups. These results were corroborated by efficacy assessment by investigators and patients. Three cases of deep venous thrombosis in heparin spraygel and 1 in heparin sc group were reported. No significant adverse reactions were observed in the spraygel group, but 1 serious allergic reaction was observed in the LMWH group. Tolerance of new formula heparin was assessed as good. Heparin spraygel-a new topical mode of heparin application, seems a promising method of heparin delivery. This initial study has demonstrated comparable efficacy and safety of LHSG and LMWH in local treatment of SVT. These findings should be confirmed by further extensive study that will reach appropriate statistical power to support such conclusion, for despite heparin treatment, significant risk of DVT was demonstrated in both groups.", "nan", "The aim of the present, randomized, placebo controlled study was to assess the dose-dependent symptom reduction efficacy, safety and tolerability of heparin-spraygel (Viatromb 2.400 IU/g heparin spraygel) in patients with superficial vein thrombosis (SVT) of the lower limbs.\n A number of clinically relevant objectives; time to onset and intensity of symptoms' reduction reflected also by rescue medication consumption were considered and assessed.\n Pain reduction between the two time-points (days 0 and 7) was significant within both treatment groups (active drug and placebo). However, subjects treated with active drug reported a mean pain reduction (VAS) of 76.21 mm (93.13% decrease); in subjects treated with placebo it was 50.36 (61.35%) mm (P<0.0001). The difference in pain reduction between the active drug and placebo groups was significant (P<0.05). The proportion of responders (subjects with at least 50%reduction in pain (VAS) on day 7 and day 14) was higher within subjects treated with Viatromb (P<0.05). The extension of erythema, evaluated by planimetry indicated a significantly higher reduction (day 0 to 7 and 0 to 14) in Viatromb-treated subjects in comparison with placebo. In the Viatromb group, the reduction in thrombus size was remarkable towards placebo (P<0.05). Reduction of edema and pain (VRS) had comparable time courses. Both investigator's and subject's global assessment of efficacy were significantly better with Viatromb. No adverse events or reactions were reported during the study and the follow up period.\n Viatromb was significantly more effective than placebo in the symptomatic treatment of SVT.", "Superficial thrombophlebitis can produce pain and result in a deep vein thrombosis (DVT) if not treated. Conservative therapies including prescription of non-steroidal anti-inflammatory drugs (NSAID) and heat have been standard care. Recently, studies have been published reporting efficacy and safety of low-molecular-weight heparin for the treatment of superficial thrombophlebitis. However, there are few comparative trials to conservative therapy. We studied the effectiveness and safety of treatment with dalteparin compared with ibuprofen in patients with confirmed superficial thrombophlebitis.\n Consecutive patients were randomized to receive daily dalteparin vs. ibuprofen three times daily for up to 14 days. The primary outcome measure was the incidence of extension of thrombus or new symptomatic venous thromboembolism during the 14-day and 3-month follow-up period. The secondary outcome was a reduction in pain. The outcome measure of safety was the incidence of major and minor bleeding.\n Of 302 consecutive patients screened, 72 were enrolled. Four patients receiving ibuprofen compared with no patients receiving dalteparin had thrombus extension at 14 days (P = 0.05), however, there was no difference in thrombus extension at 3 months. Both treatments significantly reduced pain. There were no episodes of major or minor bleeding during the treatment period.\n Dalteparin is superior to the NSAID ibuprofen in preventing extension of superficial thrombophlebitis during the 14-day treatment period with similar relief of pain and no increase in bleeding. However, questions concerning the optimal treatment duration should be explored in future trials.\n © 2012 International Society on Thrombosis and Haemostasis.", "The optimal treatment of superficial vein thrombosis (SVT) of the leg has not been determined yet. The aim of this study is to evaluate the efficacy of low-molecular-weight heparin (LMWH) as compared with combined therapy of LMWH with an anti-inflammatory agent in treatment of SVT.\n Fifty patients with SVT of the greater saphenous vein were randomly assigned to be treated with Ca-nadroparin 190 IUAxa/kg in a single dose or with same dose of Ca-nadroparin and 60 mg oral acemetacine twice daily for 10 days. The efficacy of the two treatments to relieve symptoms and signs was evaluated by using visual analogue scale.\n Significant improvements were achieved for both groups after the treatment in terms of all four symptoms (P < 0.001). Treatment scores were in favour of LMWH with anti-inflammatory agent treatment group to relieve all four symptoms. The most significant and remarkable results obtained were for the reduction of pain and local tenderness (P < 0.05). No patient experienced major complications or mortality in either group.\n The results of this study suggest that the combined therapy of LMWH with an anti-inflammatory agent is more effective than LMWH. It may be an important option in the standard treatment of SVT.", "Forty patients with superficial vein thrombosis (SVT) or thrombophlebitis were randomly treated either with defibrotide (20) an antithrombotic/profibrinolytic drug or with low-dose subcutaneous heparin [LDSH] (20) for 3 weeks. The efficacy of the two treatments was evaluated by means of computerized thermography monitoring the decrease of the areas at maximum temperature (AMT) and using an analogue scale line to evaluate signs and symptoms. Defibrotide was found to be significantly more effective than LDSH in decreasing both AMT and analogue score after 2 and 3 weeks. By enhancing endogenous fibrinolysis, defibrotide reduced the deposition of fibrin, the ensuing inflammatory response and the production of new thrombi in the affected veins. This was shown by the progressive decrease in the hyperthermic areas. Thanks to its activity defibrotide may be able to promote a faster removal of thrombi and reduce the continuous formation of new thrombi in the inflamed veins.", "The aim of the present study was to evaluate the effects of different treatment plans (compression only, early surgery, low-dose subcutaneous heparin [LDSH], low-molecular-weight heparin [LMWH], and oral anticoagulant [OC] treatment) in the management of superficial thrombophlebitis (STP), by considering efficacy and costs in a 6-month, randomized, follow-up trial. Patients with STP, with large varicose veins without any suspected/documented systemic disorder, were included. Criteria for inclusion were as follows: presence of varicose veins; venous incompetence (by duplex); a tender, indurated cord along a superficial vein; and redness and heat in the affected area. All patients were ambulatory. Exclusion criteria were obesity, cardiovascular or neoplastic diseases, bone/joint disease, problems requiring immobilization, and age > 70 years. Patients with superficial thrombophlebitis without varicose veins and patients under treatment with drugs at referral were also excluded. Color duplex (CD) was used to detect concomitant deep vein thrombosis (DVT) and to evaluate the extension or reduction of STP at 3 and 6 months. Venography was not used. Of 562 patients included, 3.5% had had a recent DVT in the same limb affected by SVT and 2.1% in the contralateral limb. In six patients DVT was present in both limbs. These patients were treated with anticoagulants and excluded from the follow-up. After 3 and 6 months the incidence of STP extension was higher in the elastic compression and in the saphenous ligation groups (p < 0.05). There was no significant difference in DVT incidence at 3 months among the treatment groups. Stripping of the affected veins was associated with the lowest incidence of thrombus extension. The cost for compression alone was the lowest and the cost including LMWH was the highest. The average cost was 1,383 US$. However the highest social cost (lost working days, inactivity) was observed in subjects treated only with stockings." ]

[ "7981078", "10755397", "8440364" ]

[ "Treatment of multiple myeloma according to the extension of the disease: a prospective, randomised study comparing a less with a more aggressive cystostatic policy. Cooperative Group of Study and Treatment of Multiple Myeloma.", "Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Cooperative Group of Study and Treatment of Multiple Myeloma.", "Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I--a randomized study. Myeloma Group of Western Sweden." ]

[ "The purpose of the study was to ascertain whether the prognostic significance of staging in multiple myeloma (MM) is influenced by the aggressiveness of effective induction treatment and/or by continuing or discontinuing maintenance chemotherapy. Patients with untreated stage I MM (defined according to Durie and Salmon) were randomised between being followed without cytostatics until the disease progressed and receiving six courses of melphalan and prednisone (MP-P) just after diagnosis; stage II patients were uniformly treated with MPH-P and stage III patients were randomised between MPH-P and four courses of combination chemotherapy with Peptichemio, vincristine and prednisone (PTC-VCR-P). Within each stage, responsive patients were randomised between receiving additional therapy only until maximal tumour reduction was reached (plateau phase) and continuing induction therapy indefinitely until relapse. With resistant, progressive or relapsing disease, patients originally treated with MPH-P for induction received combination chemotherapy and vice versa. The overall first response rate was 43.8% (42.2% in 206 stage I, II and III patients treated with MPH-P and 48.0% in 75 stage III patients treated with combination chemotherapy, P = NS). Combination chemotherapy was more myelotoxic than MPH-P and, in particular, caused more non-haematological side-effects. Both the less and the more aggressive induction policies gave the same disease control. Progression of disease was statistically similar in stage I patients who were initially left untreated and in t hose who received MPH-P just after diagnosis; median duration of first response was similar in stage III patients receiving MPH-P and in those on combination chemotherapy. In all stages, discontinuing or continuing maintenance did not alter the median duration of first response. The overall second response rate was 28.5% (34.0% to MPH-P and 25.3% to combination chemotherapy, P = NS). Median survival was greater than 78 months in stage I, was 46.3 months in stage II and was 24.3 months in stage III patients, still independent of both induction and post-induction policies. In MM, the significance of staging for survival is independent of both the aggressiveness of induction and of continuing or discontinuing maintenance chemotherapy after the maximal tumor reduction has been achieved. Both MPH-P and and the association of PTC, VCR and P are effective in inducing first response and also second response in patients failing on the alternative regimen, but PTC-VCR-P causes more side effects. Thus, the overwhelming majority of patients with MM can safely be given MPH-P as first therapy, and this treatment may be delayed in early diseases.", "We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57-2.42; P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months; P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients.", "From October 1983 until December 1988, 50 patients with asymptomatic multiple myeloma stage I were included in a prospective randomized multi-centre study comparing melphalan-prednisone (MP) therapy started at the time of diagnosis with deferred therapy where MP was started at the time of disease progression. Twenty-five patients were randomized to each group. The median time from diagnosis to start of therapy in the group with deferred therapy was 12 months. The reasons for starting therapy were increasing M-protein in 8 cases, symptomatic bone disease in 9 and anaemia in 5. In 2 cases, disease progression was complicated by vertebral fractures necessitating radiotherapy. Two patients in the group in which MP was started at the time of diagnosis developed acute leukaemia. No differences in response rate, response duration or survival were observed between the treatment groups. We conclude that in asymptomatic myeloma deferral of chemotherapy is feasible in well-informed and well-controlled patients but conveys no advantage in survival. In clinical practice the benefits of treatment deferral are to some extent outweighed by disease progression before start of treatment." ]

[ "16963828", "16118380", "12167548", "9373422", "10809268", "13129838", "16024184" ]

[ "Effects of ketamine on precipitated opiate withdrawal.", "Anesthesia-assisted vs buprenorphine- or clonidine-assisted heroin detoxification and naltrexone induction: a randomized trial.", "A comparison of antagonist-precipitated withdrawal under anesthesia to standard inpatient withdrawal as a precursor to maintenance naltrexone treatment in heroin users: outcomes at 6 and 12 months.", "Efficacy and safety of two new methods of rapid intravenous detoxification in heroin addicts previously treated without success.", "Acute detoxification of opioid-addicted patients with naloxone during propofol or methohexital anesthesia: a comparison of withdrawal symptoms, neuroendocrine, metabolic, and cardiovascular patterns.", "Rapid detoxification from opioid dependence under general anaesthesia versus standard methadone tapering: abstinence rates and withdrawal distress experiences.", "Opioid antagonist detoxification under anaesthesia versus traditional clonidine detoxification combined with an additional week of psychosocial support: a randomised clinical trial." ]

[ "N-methyl-D-aspartate antagonists were shown to be effective in suppressing the symptoms of opiate withdrawal. Intravenous anesthetic, ketamine, is the most potent N-methyl-D-aspartate antagonist available in clinical practice. The present study was designed to evaluate the effects of subanesthetic ketamine infusion, as little human data are available on ketamine in precipitated opiate withdrawal.\n A total of 58 opiate-dependent patients were enrolled in a randomized, placebo-controlled, double-blind study. Patients underwent rapid opiate antagonist induction under general anesthesia. Prior to opiate antagonist induction patients were given either placebo (normal saline) or subanesthetic ketamine infusion of 0.5 mg/kg/h. Further evaluations were divided into three phases: anesthetic, early postanesthetic (48 hours), and remote at 4 months after procedure. Cardiovascular, respiratory, renal, and gastrointestinal responses to opiate antagonist induction were monitored during anesthesia phase. Changes in plasma cortisol concentrations were measured as stress-response markers. Evaluations during early postanesthetic phase were based on Subjective and Objective Opiate Withdrawal Scales. Remote effects were assessed according to questionnaire based on Addiction Severity Index.\n Altogether, 50 patients were included in the final analysis. Ketamine group presented better control of withdrawal symptoms, which lasted beyond ketamine infusion itself. Significant differences between Ketamine and Control groups were noted in anesthetic and early postanesthetic phases. There were no differences in effects on outcome after 4 months.\n In this study, subanesthetic ketamine infusion was an effective adjuvant in the correction of acute precipitated opiate withdrawal although it had no long-term effects on treatment of opiate dependence.", "Rapid opioid detoxification with opioid antagonist induction using general anesthesia has emerged as an expensive, potentially dangerous, unproven approach to treat opioid dependence.\n To determine how anesthesia-assisted detoxification with rapid antagonist induction for heroin dependence compared with 2 alternative detoxification and antagonist induction methods.\n A total of 106 treatment-seeking heroin-dependent patients, aged 21 through 50 years, were randomly assigned to 1 of 3 inpatient withdrawal treatments over 72 hours followed by 12 weeks of outpatient naltrexone maintenance with relapse prevention psychotherapy. This randomized trial was conducted between 2000 and 2003 at Columbia University Medical Center's Clinical Research Center. Outpatient treatment occurred at the Columbia University research service for substance use disorders. Patients were included if they had an American Society of Anesthesiologists physical status of I or II, were without major comorbid psychiatric illness, and were not dependent on other drugs or alcohol.\n Anesthesia-assisted rapid opioid detoxification with naltrexone induction, buprenorphine-assisted rapid opioid detoxification with naltrexone induction, and clonidine-assisted opioid detoxification with delayed naltrexone induction.\n Withdrawal severity scores on objective and subjective scales; proportions of patients receiving naltrexone, completing inpatient detoxification, and retained in treatment; proportion of opioid-positive urine specimens.\n Mean withdrawal severities were comparable across the 3 treatments. Compared with clonidine-assisted detoxification, the anesthesia- and buprenorphine-assisted detoxification interventions had significantly greater rates of naltrexone induction (94% anesthesia, 97% buprenorphine, and 21% clonidine), but the groups did not differ in rates of completion of inpatient detoxification. Treatment retention over 12 weeks was not significantly different among groups with 7 of 35 (20%) retained in the anesthesia-assisted group, 9 of 37 (24%) in the buprenorphine-assisted group, and 3 of 34 (9%) in the clonidine-assisted group. Induction with 50 mg of naltrexone significantly reduced the risk of dropping out (odds ratio, 0.28; 95% confidence interval, 0.15-0.51). There were no significant group differences in proportions of opioid-positive urine specimens. The anesthesia procedure was associated with 3 potentially life-threatening adverse events.\n These data do not support the use of general anesthesia for heroin detoxification and rapid opioid antagonist induction.", "To compare two methods of heroin withdrawal, 51 heroin users were randomised to undergo a 1 day precipitated withdrawal procedure using naloxone under anaesthetic. About 50 participants were randomised to receive the current standard inpatient withdrawal treatment using clonidine plus symptomatic medication. Following withdrawal, both groups were offered 9 months of naltrexone treatment and supportive counselling. Outcome measures were: commencement of naltrexone, retention in treatment and heroin use at 6 and 12 months. Significantly more of the precipitated withdrawal group completed withdrawal, commenced naltrexone and stayed in treatment for the first 3 months. Overall, there was a significant reduction in both self-reported heroin use and morphine concentration in hair over the 12 month study period, with participants in the precipitated withdrawal group showing significantly lower morphine concentration at 6 months. Being younger and having a lower level of dependence were predictors of abstinence at 6 and 12 months. The advantage of precipitated withdrawal under anesthesia did not persist beyond 3 months with respect to retention in naltrexone treatment or beyond 6 months with respect to heroin use. Long-term follow-up is crucial in assessing the effects of treatment interventions for heroin dependence.", "New methods of rapid opiate detoxification, under intravenous sedation, can detoxify heroin-addicted patients in 24 hours. Their clinical application has been limited by the lack of studies establishing both efficacy and safety.\n In a randomised, controlled study, 300 treatment-refractory, heroin-addicted patients received rapid intravenous detoxification treatment (naloxone infusion, 0.06-0.08 mg/kg, then oral naltrexone 50 mg/day) under either monitored light intravenous sedation or unmonitored deep intravenous sedation.\n All patients were successfully detoxified and 93% remained abstinent one month later. Severity of withdrawal, according to the Wang Scale modified by Loimer, was 4.9 (s.d. 3.0) points in the light sedation group and 4.8 (s.d. 2.9) in the deep sedation group (P = 0.26). Two patients (1.3%) in the light sedation group and four (2.6%) in the deep sedation group required tracheal intubation (P = 0.31). There was only one severe complication, a case of nosocomial aspirative pneumonia which improved with antibiotic treatment.\n Successful rapid intravenous detoxification can be achieved using relatively light levels of sedation.", "Mu-Opioid receptor blockade during general anesthesia is a new treatment for detoxification of opioid addicted patients. We assessed catecholamine plasma concentrations, oxygen consumption, cardiovascular variables, and withdrawal symptoms after naloxone and tested the hypothesis that variables are influenced by the anesthetic administered during detoxification.\n Prospective randomized clinical study.\n Intensive care unit of a university hospital and psychiatric ward.\n Twenty-five mono-opioid addicted patients with mild to moderate systemic disease (ASA II classification) in a methadone substitution program.\n General anesthesia with either propofol (129+/-7 microg x kg(-1) x min(-1), mean +/- SEM) or methohexital (74+/-14 microg x kg(-1). min(-1)), mu-opioid receptor blockade by naloxone in a stepwise fashion (increasing doses of 0.4 mg, 0.8 mg, 1.6 mg, 3.2 mg, and 6.4 mg at 15 min intervals followed by 0.8 mg x hr(-1) for 24 hrs) and naltrexone 50 mg x day(-1) orally for > or =4 wks. Clonidine was started 180 mins after the first naloxone dose and its infusion rate was individually adjusted to mitigate withdrawal symptoms during weaning and after extubation.\n During propofol and methohexital anesthesia, naloxone induced a 30-fold increase in epinephrine and a significant three-fold increase in norepinephrine plasma concentrations without a significant difference between groups. This increase in catecholamine plasma concentrations was associated with increased oxygen consumption and marked cardiovascular stimulation with both anesthetics, as shown by increased cardiac index, heart rate, and systolic atrial pressure whereas diastolic pressure remained unchanged. Patients receiving propofol could be extubated significantly earlier after discontinuation of the anesthetics. Although the maximum degree of withdrawal symptoms (Short Opioid Withdrawal Scale) on the day after detoxification was similar with both anesthetics, subsequent withdrawal symptoms decreased significantly more rapidly after propofol anesthesia.\n Naloxone treatment, in opioid-addicted patients, induced a marked increase in catecholamine plasma concentrations, metabolism, and cardiovascular stimulation during anesthesia with both propofol and methohexital. Although both anesthetics appear suitable for detoxification treatment, the use of propofol is associated with earlier extubation and, surprisingly, a shortened period of long-term withdrawal symptoms during detoxification.", "The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioid-dependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the Novadic addiction centre in St Oedenrode and St Joseph Hospital in Veghel, the Netherlands. Thirty opioid-dependent patients took part. Outcome measures included urine toxicology screening for opiates to determine abstinence and presence of objective and subjective opioid withdrawal distress symptoms. Statistically significant differences in abstinence rate between RD-GA and SMT were present after one (RD-GA 100% vs. SMT 40%, p < 0.01) and 2 months (RD-GA 93% vs. SMT 33%, p < 0.01). After 3 months the difference in abstinence was still substantial, but no longer statistically significant (RD-GA 67% vs. SMT 33%, p = 0.14). Objective and subjective withdrawal symptoms showed largely identical outcomes and were equally low in the two groups for those who remained in the study. There was a considerably higher percentage of abstinence in the RD-GA group after 1, 2 and 3 months of follow-up accompanied by relatively mild withdrawal symptoms of shorter duration. However, if one completes SMT the data suggest a greater chance of staying clean in the long term than those completing RD-GA.", "While detoxification under anaesthesia accelerates the detoxification procedure, there is a lack of randomised clinical trials evaluating its effectiveness compared to traditional detoxification procedures, and a lack of data on long-term abstinence.\n Prospective randomised clinical trial. Analysis by intention to treat and per protocol. Setting: Specialised substance abuse unit in a psychiatric teaching hospital and an intensive care unit of a general hospital. Participants: Seventy patients with opiate mono-dependence requesting detoxification: 36 randomised to RODA (treatment as allocated received by 26) and 34 randomised to classical clonidine detoxification (treatment as allocated received by 21). Main outcome measures: Successful detoxification, safety and self-reported abstinence at 3, 6 and 12 months after detoxification.\n Socio-demographics were similar in both groups at baseline. No complications were reported during or after anaesthesia. According to the intention to treat analysis, 28/36 (78%) RODA patients and 21/34 (62%) of the clonidine group successfully completed the detoxification process (p=0.14). In the intention to treat analysis, 30% of RODA patients were abstinent after 3 months compared to 14% in the clonidine group (p=0.11). No difference was found at 6 and 12 months (both groups showed less than 5% abstinence after 12 months). The per-protocol analysis showed similar results with no statistical differences either for ASI mean scores or for the SF36 questionnaire.\n Although the detoxification success rate and abstinence after 3 months were slightly better for the RODA procedure compared to clonidine treatment, these differences were not statistically significant and disappeared completely after 6 and 12 months." ]

[ "9113932", "10944137", "11136838", "12663712", "8636768", "9704732", "7898521", "15044639", "11707834", "16157621", "12011124", "12431962", "9060555" ]

[ "High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma.", "Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study.", "Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma: randomized phase III EORTC study.", "Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin's lymphoma: an Italian multicenter randomized trial.", "High-dose chemotherapy followed by autologous bone marrow transplantation versus dexamethasone, cisplatin, and cytarabine in aggressive non-Hodgkin's lymphoma with partial response to front-line chemotherapy: a prospective randomized italian multicenter study.", "VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group.", "Comparison of CHOP chemotherapy with autologous bone marrow transplantation for slowly responding patients with aggressive non-Hodgkin's lymphoma.", "Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support.", "CHOP versus CHOP plus ESHAP and high-dose therapy with autologous peripheral blood progenitor cell transplantation for high-intermediate-risk and high-risk aggressive non-Hodgkin's lymphoma.", "Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG.", "Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma.", "Randomized study to evaluate the use of high-dose therapy as part of primary treatment for \"aggressive\" lymphoma.", "Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87-2. Groupe d'Etude des Lymphomes de l'Adulte." ]

[ "We compared a regimen of six chemotherapeutic agents administered sequentially at high doses, followed by myeloablative treatment and bone marrow transplantation, with a regimen of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as initial or salvage treatment for adults with diffuse large-cell lymphoma.\n Ninety-eight eligible patients with diffuse large-cell lymphoma of the B-cell type were randomly assigned to receive either MACOP-B (50 patients) or high-dose sequential therapy (48 patients). The study design allowed for patients in whom the assigned treatment failed to cross over to the other treatment group.\n After a median follow-up of 55 months, the patients given high-dose sequential therapy, as compared with those treated with MACOP-B, had significantly higher rates of complete response (96 percent vs. 70 percent, P=0.001), freedom from disease progression (84 percent vs. 49 percent, P<0.001), freedom from relapse (88 percent vs. 70 percent, P=0.055), and event-free survival (76 percent vs. 49 percent, P=0.004). The difference in overall survival at seven years, which also favored the group assigned to high-dose sequential therapy, was marginally significant (81 percent vs. 55 percent, P=0.09).\n High-dose sequential therapy is superior to standard-dose MACOP-B for patients with diffuse large-cell lymphoma of the B-cell type.", "To present the final analysis, with a median follow-up of 8 years, of the LNH87-2 randomized study, which compares consolidative sequential chemotherapy (ifosfamide plus etoposide, asparaginase, and cytarabine) with high-dose therapy (HDT) using cyclophosphamide, carmustine, and etoposide (CBV regimen) followed by stem-cell transplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission after induction, focusing on high/intermediate- and high-risk patients identified by the age-adjusted international prognostic index.\n Among the 916 eligible patients, 451 presented with two (n = 318) or three (n = 133) risk factors. After reaching complete remission to induction therapy, 236 of these higher risk patients were assessable for the consolidation phase, with 125 patients in the HDT arm and 111 in the sequential chemotherapy arm.\n Among these 451 higher risk patients, 277 (61%) achieved complete remission after induction treatment. In the population of 236 randomized patients, HDT was superior to sequential chemotherapy, with 8-year disease-free survival rates of 55% (95% confidence interval [CI], 46% to 64%) and 39% (95% CI, 30% to 48%), respectively (P =.02; relative risk, 1.56). The 8-year survival rate was significantly superior in the HDT arm (64%; 95% CI, 55% to 73%) compared with the sequential chemotherapy arm (49%; 95% CI, 39% to 59%) (P =.04; relative risk, 1.51).\n On the basis of the final analysis of this prospectively treated series of patients, retrospectively analyzed on the basis of the International Prognostic Index, we hypothesize that HDT benefits patients at higher risk who achieve complete remission after induction treatment.", "The long-term outcome for patients with aggressive non-Hodgkin's lymphoma (NHL) is poor. Consequently, the European Organization for Research and Treatment of Cancer Lymphoma Group designed a prospective randomized trial to investigate whether high-dose chemotherapy plus autologous bone marrow transplantation (ABMT) after standard combination chemotherapy improves long-term survival.\n Patients aged 15-65 years with aggressive NHL received three cycles of CHVmP/BV polychemotherapy (i.e., a combination of cyclophosphamide, doxorubicin, teniposide, and prednisone, with bleomycin and vincristine added at mid-cycle). After these three cycles, patients with a complete or partial remission and at that time no lymphoma involvement in the bone marrow were randomly assigned to the ABMT arm (a further three cycles of CHVmP/BV followed by BEAC [i.e., a combination of carmustine, etoposide, cytarabine, and cyclophosphamide] chemotherapy and ABMT) or to the control arm (five more cycles of CHVmP/BV). All statistical tests are two-sided.\n From December 1990 through October 1998, 311 patients (median age = 44 years) were registered and received the first three cycles of CHVmP/BV, and 194 patients were randomly assigned to the treatment arms. Approximately 70% (140 patients) of these patients were of low or low-intermediate International Prognostic Index (IPI) risk. After a median follow-up of 53 months, an intention-to-treat analysis showed a time to disease progression and overall survival at 5 years of 61% (95% confidence interval [CI] = 51% to 72%) and 68% (95% CI = 57% to 79%), respectively, for the ABMT arm and 56% (95% CI = 45% to 67%) and 77% (95% CI = 67% to 86%), respectively, for the control arm. Differences between arms were not statistically significant. A subset analysis on IPI risk groups, although too small for reliable statistical analysis, yielded similar results.\n Standard combination therapies remain the best choice for most patients with aggressive NHL. We recommend that patients with IPI low or low-intermediate risk not be subjected to high-dose chemotherapy and ABMT as a first-line therapy.", "To evaluate the role of early intensification with high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) as front-line chemotherapy for patients with high-risk, histologically aggressive non-Hodgkin's lymphoma (NHL).\n We planned a multicenter, randomized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B; arm A) with an abbreviated regimen of MACOP-B (8 weeks) followed by HDT and ASCT (arm B) for intermediate-high-risk/high-risk patients (according to the age-adjusted International Prognostic Index). From September 1994 to April 1998, 150 patients with aggressive lymphoma were enrolled onto the trial. Seventy-five patients were randomly assigned to arm A and 75 patients were randomly assigned to arm B. In both arms, involved-field radiation therapy (36 Gy) was delivered to the site of bulky disease.\n The rate of complete response was 68% in arm A and 76% in arm B (P = not significant [NS]). Three toxic deaths (4%) occurred in arm B and one (1%) occurred in arm A (P = NS). In arm B, 30 patients (40%) did not undergo HDT and ASCT. According to the intention-to-treat analysis at a median follow-up of 24 months, 5-year overall survival probability in arms A and B was 65% and 64% (P =.95), 5-year progression-free survival was 49% and 61% (P =.21), and 5-year relapse-free survival was 65% and 77% (P =.22), respectively.\n Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk, aggressive NHL. Additional randomized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients.", "To evaluate, in a prospective multicentric study, the efficacy of a conventional salvage chemotherapy (dexamethasone, cisplatin, and cytarabine [DHAP]) versus high-dose chemotherapy (carmustine, etoposide, cytarabine, and cyclophosphamide [BEAC]) followed by autologous bone marrow transplantation (ABMT) in patients with aggressive non-Hodgkin's lymphoma (NHL) in clinical partial response (PR) after two thirds of a conventional front-line therapy.\n From August 1988 to August 1991, 286 patients with aggressive NHL were randomized in seven Italian institutions to receive fluorouracil, methotrexate, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP) or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as front-line therapy. Of the 286 patients enrolled onto the trial, 77 (27%) were considered in PR after two thirds of the front-line therapy, and 49 of 77 (64%) were randomized: 27 to receive DHAP chemotherapy and 22 to receive BEAC followed by ABMT.\n The response after second-line treatment was as follows: in the DHAP group, four patients (15%) achieved a complete remission (CR), 12 (44%) remained in stable PR, and 11 (41%) showed progressive disease; in the ABMT group, three patients (14%) obtained a CR, 18 (82%) obtained a stable PR, and one (4%) progressed, with an overall response (CR + stable PR) of 59% and 96% (P < .001) in the DHAP and ABMT groups, respectively. The overall survival was 59% versus 73% and the progression-free survival (PFS) was 52% versus 73% in the DHAP and ABMT groups, respectively (P, not significant). The toxicity was mild, particularly in the ABMT group, and no treatment-related deaths occurred in either group.\n Because of the small number of patients randomized, we were unable to determine whether ABMT or a standard salvage regimen (DHAP) is superior for PR patients. However, we confirmed that myeloablative treatment is a safe and well-tolerated procedure in this category of patients and this may enable us to evaluate its role as part of a front-line treatment in poor-risk NHL patients.", "The aim of this multicenter randomized study was to compare conventional therapy with conventional plus high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) as front-line treatment for poor-prognosis non-Hodgkin's lymphoma (NHL).\n Between October 1991 and June 1995, 124 patients, aged 15 to 60 years, with diffuse intermediate- to high-grade NHL (Working Formulation criteria), stages II bulky (> or = 10 cm), III, or IV were enrolled. Sixty-one patients were randomized to receive etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) for 12 weeks and cisplatin, cytarabine, and dexamethasone (DHAP) as a salvage regimen (arm A), and 63 to receive VACOP-B for 12 weeks plus HDT and ABMT (Arm B).\n There was no significant difference in terms of complete remissions (CRS) in the two groups: 75% in arm A, and 73% in arm B. The median follow-up observation time was 42 months. The 6-year survival probability was 65% in both arms. There was no difference in disease-free survival (DFS) or progression-free survival (PFS) between the two groups. DFS was 60% and 80% (P = .1) and PFS was 48% and 60% (P = .4) for arms A and B, respectively. Procedure feasibility was the major problem. In arm B, 29% of enrolled patients did not undergo HDT and ABMT. A statistical improvement in terms of DFS (P = .008) and a favorable trend in terms of PFS (P = .08) for intermediate-/high- plus high-risk group patients assigned to HDT and ABMT was observed.\n In this study, conventional chemotherapy followed by HDT and ABMT as front-line therapy seems no more successful than conventional treatment in terms of overall results. However, our results suggest that controlled studies of HDT plus ABMT should be proposed for higher risk patients.", "High-dose chemoradiotherapy combined with autologous bone marrow transplantation can cure patients with disseminated, aggressive non-Hodgkin's lymphoma in whom first-line chemotherapy has failed. In contrast, cure is rare with second-line chemotherapy. It has been suggested that patients with slow responses to the initial phase of first-line chemotherapy are at high risk for relapse. Therefore, such patients are potential candidates for early bone marrow transplantation.\n To investigate whether patients with slow responses, defined as only a partial response after three courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), would benefit from early transplantation, we conducted a prospective, randomized trial. The early application of high-dose chemoradiotherapy and autologous bone marrow transplantation was compared with the continuation of CHOP therapy for another five courses. Patients with complete responses after three courses of CHOP (fast responses) and patients who responded partially but still had tumor-positive marrow continued with another five courses of CHOP. The study end points were the response rate, overall survival, disease-free survival, and event-free survival.\n Of 286 patients who could be evaluated for the rapidity of their response after three courses of CHOP, 38 percent had fast responses, 47 percent had slow responses, and 15 percent had no response. Among 106 patients with slow responses who had lymphoma-negative marrow, 69 patients (65 percent) were randomized. Seventy-four percent of the CHOP group and 68 percent of the transplantation group had complete remissions (P = 0.54). At four years the rates of overall, disease-free, and event-free survival were 85, 72, and 53 percent, respectively, in the CHOP group and 56, 60, and 41 percent in the transplantation group (P > 0.10). The disease-free survival in both groups did not differ significantly from that of nonrandomized patients with fast responses (54 percent at four years).\n The early application of high-dose, marrow-ablative chemoradiotherapy with autologous bone marrow transplantation does not improve the outcome in patients with aggressive non-Hodgkin's lymphoma that responds slowly to first-line CHOP chemotherapy.", "The efficacy of first-line intensive chemotherapy plus transplantation of autologous hematopoietic stem cells in adults with disseminated aggressive lymphoma is unknown.\n We compared high-dose therapy plus autologous stem-cell support with the standard regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in a randomized trial. The patients were 15 to 60 years of age, had untreated aggressive lymphoma, and were at low, low intermediate, or high intermediate risk of death (i.e., a maximum of two adverse prognostic factors) according to the age-adjusted International Prognostic Index. The primary outcome was event-free survival at five years.\n Of 207 consecutive patients, 197 underwent randomization; 99 were assigned to receive CHOP, and 98 to receive high-dose chemotherapy plus stem-cell transplantation. Overall, 78 percent of the patients completed the assigned treatment; the median follow-up was four years. The estimated event-free survival rate (+/-SD) at five years was significantly higher among patients who received high-dose therapy than among patients who received CHOP (55+/-5 percent vs. 37+/-5 percent, P=0.037). Among patients with a high intermediate risk of death, according to the age-adjusted International Prognostic Index, the five-year survival rate was significantly higher after high-dose therapy than after CHOP (74+/-6 percent vs. 44+/-7 percent, P=0.001).\n High-dose chemotherapy with autologous stem-cell support is superior to CHOP in adults with disseminated aggressive lymphoma.\n Copyright 2004 Massachusetts Medical Society", "The purpose of the study was to compare conventional cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy with CHOP (3 courses) plus etoposide/methylprednisolone/high-dose cytarabine/cisplatin (ESHAP), high-dose therapy (HDT), and autologous peripheral blood progenitor cell transplantation (PBPCT) as front-line treatment for poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). Between May 1, 1995, and April 30, 1998, 58 patients, aged 15-55 years, newly diagnosed with poor-prognosis aggressive NHL (category F-H by the Working Formulation) were enrolled. According to the age-adjusted international prognostic index, 65% of the patients were high-risk cases and 35% made up the high-intermediate group. After 3 courses of CHOP, 25 of 48 patients were randomized to continue with CHOP, and 23 were randomized to receive 2-4 cycles of ESHAP followed by HDT and PBPCT. There was no significant difference in the rate of complete remission between the two groups (36%, 95% confidence interval [CI]: 18%-57% in CHOP vs. 43%, 95% CI: 23%-65% in ESHAP/HDT) (P = 0.77). With a median follow-up duration of 39 months, the 4-year failure-free survival (FFS) was superior in the ESHAP/HDT group (38%, 95% CI: 18%-58% vs. 15%, 95% CI: 4%-32%) (P = 0.04). The disease-free survival was marginally different in favor of the ESHAP/HDT arm (90%, 95% CI: 47%-98% vs. 37%, 95% CI: 7%-69%) (P = 0.06). The 4-year overall survival between the two treatment arms was comparable (51%, 95% CI: 28%-70% for ESHAP/HDT vs. 30%, 95% CI: 13%-48% for CHOP) (P = 0.25). Treatment-related mortalities were not significantly different between both groups (17%, 95% CI: 5%-39% for ESHAP/HDT vs. 8%, 95% CI: 1%-26% for CHOP) (P = 0.41). However, only 61% of the patients assigned to the ESHAP/HDT arm underwent HDT and PBPCT. As compared with CHOP, the corporate regimen of CHOP/ESHAP/HDT seems to improve the FFS in patients with newly diagnosed, poor-prognosis aggressive NHL.", "There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL.\n Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B).\n According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement.\n Aggressive NHL patients do not benefit from upfront HDS/HDT.", "Randomized trial LNH93-3 was conducted on patients who had poor-prognosis aggressive lymphoma and were younger than 60 years with two to three factors of the age-adjusted International Prognostic Index to evaluate the benefit of early high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT).\n Patients were randomized between doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) chemotherapy followed by sequential consolidation and an experimental shortened treatment consisting of three cycles with escalated doses of cyclophosphamide, epirubicin, vindesine, bleomycin, and prednisone and collection of peripheral-blood stem cells. On day 60, HDT was administered with 1,3-bis(2-chloroethyl)-1-nitrosourea, etoposide, cytarabine, and melphalan followed by ASCT.\n Eligible patients (n = 370) with aggressive lymphoma were analyzed. For ACVBP (181 patients) and HDT (189 patients), respective complete remission rates were 64% and 63%. With a median follow-up of 60 months, 5-year overall survival and event-free survival for ACVBP and HDT were 60% +/- 8% and 46% +/- 8% (P =.007) and 52 +/- 8% and 39 +/- 8% (P =.01), respectively. Survival was independently affected by age greater than 40 years (P =.0003), T-cell phenotype (P =.009), bone marrow involvement (P =.003), and HDT treatment group (P =.04).\n Early HDT with ASCT in high-risk patients was inferior to the ACVBP chemotherapy regimen. These results indicate that the received dose-intensity before HDT was too low when compared with ACVBP and HDT and was given too early.", "This trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study.\n Three hundred twelve patients with \"aggressive\" non-Hodgkin's lymphoma aged <or= 60 years with elevated serum lactate dehydrogenase levels were included from 1990 to 1997. Patients with at least a minor response after two cycles of CHOEP (CHOP + etoposide 3 x 100 mg/m(2)) were to receive three further cycles of CHOEP followed by IF radiotherapy (arm A) or one further cycle of CHOEP followed by autologous stem-cell transplantation and IF radiotherapy (arm B).\n Among 158 patients randomized to arm B, 103 (65%) received HDT. The complete remission rate at the end of treatment was 62.9% in arm A and 69.9% in arm B. With a median observation time of 45.5 months, overall survival for all 312 patients was 63% after 3 years (63% for arm A, 62% for arm B; P =.68). Event-free survival was 49% for arm A versus 59% for arm B (P =.22). Relapse in arm B was associated with a significantly worse survival rate than relapse in arm A (P <.05). Relapse after HDT occurred early (median interval, 3 months). Six patients developed secondary neoplasia, three in arm A and three in arm B.\n Results of the randomized trial comparing CHOP-like chemotherapy with early HDT do not support the use of HDT with carmustine, etoposide, cytarabine, and melphalan following shortened standard chemotherapy.", "To update the randomized study that compared consolidative sequential treatment (ifosfamide, etoposide, asporaginase, and cytarabine) versus the high-dose regimen of cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission and to focus on high-intermediate and high-risk patients identified by the international prognostic index.\n Nine hundred sixteen patients received induction treatment on the LNH84 protocol with open randomization for the anthracycline. In a subsequent randomization, 541 patients in complete remission were assigned to receive consolidation by either sequential chemotherapy (n = 273) or autotransplant (n = 268). Among the higher risk population (two or three risk factors), 236 patients in complete remission were assessable for the consolidation phase, with 111 in the sequential chemotherapy arm and 125 in the autotransplant arm.\n Among 541 randomized patients, disease-free survival and survival did not differ significantly between the two consolidative treatment arms. In the higher risk population, CBV was superior to sequential chemotherapy, with 5-year disease-free survival rates of 59% (95% confidence interval, 49% to 69%) and 39% (95% confidence interval, 28% to 50%), respectively (P = .01, relative risk = 1.19). The 5-year survival rate was superior in the CBV group at 65% (95% confidence interval, 56% to 74%) compared with 52% in the sequential chemotherapy group (95% confidence interval, 42% to 62%) (P = .06, relative risk = 1.49).\n This study shows a superior disease-free survival for higher risk patients in complete remission. Dose-intensive consolidation therapy should be considered for patients at higher risk who achieve complete remission after induction treatment." ]

[ "15082468", "11465710", "12546607", "15308513", "11754710", "15249319", "2052056", "15940774", "14999359", "8216413" ]

[ "Patient Preference for Placebo, Acetaminophen (paracetamol) or Celecoxib Efficacy Studies (PACES): two randomised, double blind, placebo controlled, crossover clinical trials in patients with knee or hip osteoarthritis.", "A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee.", "Lack of efficacy of acetaminophen in treating symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled comparison trial with diclofenac sodium.", "The IPSO study: ibuprofen, paracetamol study in osteoarthritis. A randomised comparative clinical study comparing the efficacy and safety of ibuprofen and paracetamol analgesic treatment of osteoarthritis of the knee or hip.", "Efficacy of rofecoxib, celecoxib, and acetaminophen in osteoarthritis of the knee: a randomized trial.", "Paracetamol in osteoarthritis of the knee.", "Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee.", "Efficacy of rofecoxib, celecoxib, and acetaminophen in patients with osteoarthritis of the knee. A combined analysis of the VACT studies.", "Analgesic efficacy and safety of nonprescription doses of naproxen sodium compared with acetaminophen in the treatment of osteoarthritis of the knee.", "Comparison of naproxen and acetaminophen in a two-year study of treatment of osteoarthritis of the knee." ]

[ "Acetaminophen (paracetamol) is recommended as the initial pharmacological treatment for knee or hip osteoarthritis. However, survey and clinical trial data indicate greater efficacy for non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 specific inhibitors.\n Two randomised, double blind, placebo controlled, crossover multicentre clinical trials, Patient Preference for Placebo, Acetaminophen or Celecoxib Efficacy Studies (PACES).Patients: Osteoarthritis of knee or hip.Intervention: \"Wash out\" of treatment; randomisation; 6 weeks of celecoxib 200 mg/day, acetaminophen 1000 mg four times a day, or placebo; second \"wash out;\" crossover to 6 weeks of second treatment.Measurements: Western Ontario McMaster Osteoarthritis Index (WOMAC), visual analogue pain scale, patient preference between two treatments.\n Celecoxib was more efficacious than acetaminophen in both periods in both studies; WOMAC and pain scale scores differed at p<0.05 in period II and both periods combined of PACES-a and in periods I and II and both periods combined in PACES-b, but not in period I of PACES-a. Acetaminophen was more efficacious than placebo, generally p<0.05 in PACES-b, and >0.05 in PACES-a. Patient preferences were 53% celecoxib v 24% acetaminophen in PACES-a (p<0.001) and 50% v 32% in PACES-b (p = 0.009); 37% acetaminophen v 28% placebo in PACES-a (p = 0.340) and 48% v 24% in PACES-b (p = 0.007). No clinically or statistically significant differences were seen in adverse events or tolerability among the three treatment groups.\n Greater efficacy was seen for celecoxib v acetaminophen v placebo, while adverse events and tolerability were similar. Variation in results and statistical significance in the two different trials are of interest.", "To perform a randomized, double-blind, crossover clinical trial of diclofenac + misoprostol versus acetaminophen in ambulatory patients with osteoarthritis of the hip or knee.\n Patients in 12 ambulatory care settings were eligible if they were age >40 years and if they had Kellgren/Lawrence radiographic grade 2-4 osteoarthritis of the knee or hip and a score of > or =30 mm on a 100-mm visual analog pain scale. Patients were randomized to one of two groups, 75 mg diclofenac + 200 microg misoprostol twice daily or 1,000 mg acetaminophen 4 times daily (each for 6 weeks), and were then crossed over to the other treatment for 6 weeks. A placebo was included in each treatment regimen to enable double blinding. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index and the visual analog pain scale of the Multidimensional Health Assessment Questionnaire. Safety was assessed using a standard form to review adverse events.\n We enrolled 227 patients, of whom 218 provided data for the first treatment period and 181 provided data for both treatment periods. Significantly higher levels of improvement in the primary outcomes were seen for diclofenac + misoprostol than for acetaminophen (P < 0.001). Adverse events were more common when patients took diclofenac + misoprostol (P = 0.046). Diclofenac + misoprostol was rated as \"better\" or \"much better\" by 57% of the 174 patients who provided such ratings for both treatment periods, while acetaminophen was rated as \"better\" or \"much better\" by 20% of these patients, and 22% reported no difference (P < 0.001). Differences favoring diclofenac + misoprostol over acetaminophen were greater in patients with more severe osteoarthritis according to baseline pain scores, radiographs, or number of involved joints.\n Patients with osteoarthritis of the hip or knee had significantly greater improvements in pain scores over 6 weeks with diclofenac + misoprostol than with acetaminophen, although patients with mild osteoarthritis had similar improvements with both drugs. Acetaminophen was associated with fewer adverse events.", "Recommendations state that acetaminophen should be used in preference to nonsteroidal anti-inflammatory drugs in the initial treatment of symptomatic osteoarthritis (OA) of the hip or knee, because of lesser toxicity and the pervasive belief that acetaminophen is not only effective in treating OA pain but is of equal analgesic efficacy as nonsteroidal anti-inflammatory drugs.\n This was a randomized, double-blind, placebo-controlled trial of diclofenac sodium, 75 mg twice daily, vs acetaminophen, 1000 mg 4 times daily, in 82 subjects with symptomatic OA of the medial knee. Osteoarthritis was quantitated radiographically, and subjects met stringent baseline pain criteria. The primary evaluation of efficacy used the Western Ontario and McMaster Universities Osteoarthritis Index, with evaluations at screening, baseline, and 2 and 12 weeks after treatment. Intention-to-treat analysis was used.\n Twenty-five subjects were randomized to diclofenac, 29 to acetaminophen, and 28 to placebo. The groups were closely matched for age, sex, body mass index, prior use of OA medications, baseline pain, and radiographic features. At 2 and 12 weeks, clinically and statistically significant (P<.001) improvements were seen in the diclofenac-treated group; however, no significant improvements were seen in the acetaminophen-treated group (P =.92 at 2 weeks and.19 at 12 weeks). Stratification of subjects according to baseline pain, prestudy OA medication, and radiographic grade showed no clear pattern of preferential response to diclofenac, and did not reveal a subset of subjects who responded to acetaminophen.\n Diclofenac is effective in the symptomatic treatment of OA of the knee, but acetaminophen is not. A review of the literature reveals that there is scanty published evidence for a therapeutic effect of acetaminophen relative to placebo in patients with OA of the knee, because most published studies use active comparators (ie, nonsteroidal anti-inflammatory drugs) only. The advocacy of acetaminophen use in subjects with OA of the knee should be reconsidered pending further placebo-controlled studies.", "To compare the analgesic efficacy of single and multiple doses of ibuprofen with that of paracetamol in patients with knee or hip osteoarthritis (IPSO study).\n 222 patients were randomised in a double blind, multicentre study-156 (70%) had a painful knee joint and 66 (30%) a painful hip joint. The main efficacy criterion was pain intensity assessment after a single dose (ibuprofen 400 mg, paracetamol 1000 mg). Functional disability assessment and patient global assessment were carried out over 14 days.\n The sum of the pain intensity difference over 6 hours after the first administration was significantly higher (p = 0.046) in the ibuprofen group than in the paracetamol group. Over 14 days pain intensity decreased from the first day and was significantly lower in the ibuprofen group than in the paracetamol group (p<0.05). The functional disability of the patient was assessed using the WOMAC; the ibuprofen group improved significantly over 2 weeks compared with the paracetamol group for each of the subscales: stiffness (p<0.002), pain (p<0.001), physical function (p<0.002). The drugs were equally safe.\n The IPSO study shows that for the treatment of osteoarthritic pain, ibuprofen 400 mg at a single and multiple dose (1200 mg/day) for 14 days is more effective than paracetamol, either as a single dose of 1000 mg or a multiple dose (3000 mg/day). Because ibuprofen and paracetamol have similar tolerability, this study indicates that the efficacy/tolerability ratio of ibuprofen is better than that of paracetamol in this indication over 14 days.", "Osteoarthritis (OA) is often treated with nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or specific inhibitors of cyclooxygenase 2 (COX-2).\n To assess the relative therapeutic efficacy of rofecoxib, celecoxib, and acetaminophen in adults with OA.\n Randomized, parallel-group, double-blind trial, conducted from June 1999 to February 2000, in 29 clinical centers in the United States.\n Three hundred eighty-two patients aged at least 40 years who had OA of the knee that was previously treated with NSAIDs or acetaminophen.\n Patients were randomly assigned to receive rofecoxib, 12.5 mg/d (n = 96); rofecoxib, 25 mg/d (n = 95); celecoxib, 200 mg/d (n = 97); or acetaminophen, 4000 mg/d (n = 94) for 6 weeks.\n Assessments over days 1 to 6 and over 6 weeks included pain on walking, night pain, pain at rest, and morning stiffness as measured on a Western Ontario McMaster Universities Osteoarthritis Index (100-mm visual analog scale [VAS]) and global response to therapy compared among 4 treatment groups.\n 79% of patients completed the study. More patients treated with acetaminophen discontinued early due to lack of efficacy than patients treated with COX-2 inhibitors (31% vs 18%-19%). Efficacy assessed in the first 6 days of therapy showed greatest response to rofecoxib, 25 mg/d, followed by rofecoxib, 12.5 mg/d, celecoxib, and acetaminophen, respectively, in terms of relief of pain on walking (-32.2, - 29.0, - 26.4, and -20.6 mm change on the VAS; P</=.04 for all others vs acetaminophen; P =.05 for 25-mg rofecoxib vs celecoxib), rest pain (-21.8, - 18.6, - 15.5, and - 12.5 mm; P</=.02 for either dose of rofecoxib vs acetaminophen and P =.02 for rofecoxib, 25 mg/d, vs celecoxib), night pain (-25.2, - 22.0, - 18.7, and - 18.8 mm; P =.04 for rofecoxib, 25 mg/d, vs both acetaminophen and celecoxib), and morning stiffness (-30.4, - 28.4, - 25.7, and - 20.9 mm; P</=.02 for either dose of rofecoxib vs acetaminophen). Over 6 weeks, rofecoxib, 25 mg/d, provided greatest response for night pain (P<.002 vs celecoxib and P =.006 vs acetaminophen and P =.02 vs rofecoxib, 12.5 mg/d), composite pain subscale (P</=.03 vs all other treatments), stiffness subscale (P</=.04 vs celecoxib and acetaminophen), and physical function subscale (P =.001 vs acetaminophen). Global responses over 6 weeks showed a similar pattern (good or excellent response at week 6: 60%, 56%, 46%, and 39%, respectively; P</=.03 for rofecoxib, 25 mg/d, vs celecoxib and acetaminophen; P =.02 for rofecoxib, 12.5 mg/d, vs acetaminophen). All treatments were generally safe and well tolerated.\n Rofecoxib, 25 mg/d, provided efficacy advantages over acetaminophen, 4000 mg/d, celecoxib, 200 mg/d, and rofecoxib, 12.5 mg, for symptomatic knee OA.", "Paracetamol is a recommended symptomatic treatment of osteoarthritis (OA), but in clinical trials sample sizes have been relatively small and variable daily doses of paracetamol have been used.\n To determine the therapeutic efficacy of paracetamol in OA of the knee and identify predictive factors of clinical response to treatment.\n A double blind, parallel group, placebo controlled trial of analgesic efficacy and safety of paracetamol versus placebo including 779 patients with OA of the knee. Patients were randomly assigned to receive paracetamol 4 g/day (n = 405) or placebo (n = 374) for 6 weeks. Symptomatic OA of the knee was required at inclusion with global pain intensity of the knee during physical activities for the past 24 hours of >or=30 mm on a 100 mm visual analogue scale. The primary end point was a 30% decrease of global pain intensity of the knee. Intention to treat analyses were performed.\n The percentage of responders did not differ significantly between groups: 52.6% and 51.9% in paracetamol and placebo groups, respectively (p = 0.840). In a subgroup of patients with chronic mechanical knee pain without signs of inflammation (n = 123), the mean change in pain intensity from baseline was 25.2 mm v 15.2 mm, in the paracetamol (n = 63) and placebo (n = 60) groups, respectively-mean difference 10.0 mm; 95% CI 1.0 to 19.0; p = 0.0294. No serious adverse events were attributable to treatment.\n A statistically significant symptomatic effect of oral paracetamol 4 g/day over placebo was not found, suggesting that paracetamol use in symptomatic OA of the knee should be further explored. The tolerability and safety of paracetamol, at the recommended maximum dose of 4 g/day, was confirmed over 6 weeks.", "The optimal short-term, symptomatic therapy for osteoarthritis of the knee has not been fully determined. Accordingly, we compared the efficacy of a nonsteroidal antiinflammatory drug, ibuprofen, given in either an antiinflammatory dose (high dose) or an analgesic dose (low dose), with that of acetaminophen, a pure analgesic.\n In a randomized, double-blind trial, 184 patients with chronic knee pain due to osteoarthritis were given either 2400 or 1200 mg of ibuprofen per day or 4000 mg of acetaminophen per day. They were evaluated after a washout period of three to seven days before the beginning of the study, and again after four weeks of treatment. The major measures of outcome included scores on the pain and disability scales of the Stanford Health Assessment Questionnaire (range of possible scores, 0 to 3), scores on the visual-analogue scales for pain at rest and pain while walking, the time needed to walk 50 ft (15 m), and the physician's global assessment of the patient's arthritis.\n Seventy-eight percent of the patients completed four weeks of therapy. No significant differences were noted among the three treatment groups with respect to failure to complete the trial because of noncompliance or adverse events. All three groups had improvement in all major outcome variables, and the groups did not differ significantly in the magnitude of improvement in most variables. The mean improvement (change) in the scores on the pain scale of the Health Assessment Questionnaire was 0.33 with acetaminophen (95 percent confidence interval, 0.14 to 0.52), 0.30 with the low dose of ibuprofen (95 percent confidence interval, 0.09 to 0.51), and 0.35 with the high dose of ibuprofen (95 percent confidence interval, 0.13 to 0.57). Side effects were minor and similar in all three groups.\n In short-term, symptomatic treatment of osteoarthritis of the knee, the efficacy of acetaminophen was similar to that of ibuprofen, whether the latter was administered in an analgesic or an antiinflammatory dose.", "To compare efficacy among 1578 patients with osteoarthritis randomized to take acetaminophen 4000 mg (n=269), celecoxib 200 mg (n=523), rofecoxib 12.5 mg (n=259), or rofecoxib 25 mg (n=527) in a double blind trial [Vioxx, Acetaminophen, Celecoxib Trial (VACT2)]. Results were also pooled with the similarly designed VACT1 trial.\n Patients evaluated over Days 1 to 6 and 6 weeks with Patient Global Assessment of Response to Therapy (PGART) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index.\n For VACT2, median time to good or excellent PGART response was 6, 5, 4, and 3 days for acetaminophen, celecoxib, rofecoxib 12.5 mg, and rofecoxib 25 mg (COX-2 inhibitors vs acetaminophen, p<or=0.035; rofecoxib 25 mg vs celecoxib, p=0.01). WOMAC response over the first 6 days was greater (p < 0.05) with both rofecoxib doses than acetaminophen and celecoxib. At Week 6, all COX-2 inhibitors provided significantly greater efficacy than acetaminophen. Good or excellent PGART was numerically, but not significantly, greater with rofecoxib 25 mg (55.4%) than celecoxib (50.6%) at Week 6; a significant difference was seen at Weeks 2 (6.9, p=0.022) and 4 (6.7, p=0.027) and over 6 weeks with analysis of all 5 PGART categories of response (p=0.035). Rofecoxib 25 mg provided greater response (p<0.05) than celecoxib on WOMAC subscales. Pooled analysis of VACT1/VACT2 demonstrated greater PGART (p=0.023) with rofecoxib 25 mg (56.1%) than celecoxib (49.8%) at 6 weeks and greater response to all other PGART and WOMAC endpoints, and confirmed superiority of COX-2 inhibitors to acetaminophen. Overall, tolerability of the study medications was generally good and similar. There was no significant difference between treatment groups in the percentage of patients who experienced a clinical adverse experience (AE). The incidence of discontinuations due to an AE was significantly lower with celecoxib (2.5%) compared to rofecoxib 25 mg (6.3%, p=0.004) or acetaminophen (7.8%, p< 0.001), and did not differ significantly from rofecoxib 12.5 mg (4.6%). Discontinuation rates due to edema and hypertension related AE were similar among all COX-2 inhibitors.\n Rofecoxib and celecoxib provided superior efficacy to acetaminophen. There was a more rapid and greater response with rofecoxib 25 mg than celecoxib 200 mg. Rofecoxib 12.5 mg demonstrated greater efficacy than celecoxib 200 mg over the first 6 days, and was similar over 6 weeks. All study medications were generally well tolerated.", "Nonprescription doses of naproxen sodium, acetaminophen, and placebo were compared to determine their efficacy and safety in osteoarthritis of the knee. In two identical multicenter, randomized, double-blind, placebo-controlled, multidose, parallel-design studies, patients with osteoarthritis aged (mean +/- SD) 60.6 +/- 12.8 years were randomized to daily doses of 660 mg naproxen sodium (440 mg naproxen sodium in patients >or=65 years), 4000 mg acetaminophen, or placebo for 7 days. Naproxen sodium (440/660 mg) provided significantly greater improvements in pain at rest, on passive motion, on weight-bearing, stiffness after rest (morning), day and night pain compared with placebo, and significantly greater relief from resting pain than acetaminophen (P < 0.05). Acetaminophen provided significantly greater improvements in day pain compared with placebo. Daily evaluations showed naproxen sodium (440/660 mg) provided superior pain relief to acetaminophen and was significantly better than acetaminophen at reducing difficulties experienced in walking several blocks and difficulties in bending, lifting, and stooping. Naproxen sodium (440/660 mg) and acetaminophen (4000 mg) were significantly more effective than placebo in improving mobility level, household tasks, and walking and bending. Patient and investigator evaluation scores were significantly higher in naproxen sodium and acetaminophen groups compared with placebo; no differences were observed between active treatments. Naproxen sodium and acetaminophen had similar safety profiles to placebo. Nonprescription doses of naproxen sodium (440/660 mg) effectively relieve pain and other symptoms of osteoarthritis. Naproxen sodium is an alternative in the initial treatment of osteoarthritis and may be preferred to acetaminophen as first-line therapy in patients with moderate or severe pain.", "To compare the relative safety and efficacy of naproxen and acetaminophen in the treatment of osteoarthritis (OA) of the knee. The major outcome measures were radiographic progression and withdrawal from the trial due to lack of efficacy.\n One hundred seventy-eight patients with OA of the knee were enrolled in a 2-year prospective, controlled, double-blind multicenter trial and were randomly assigned to receive acetaminophen (ACT) or naproxen (NPX) treatment.\n After 6 weeks of treatment, modest improvement in pain on motion and in physician's global assessment was seen in both the ACT and the NPX groups, and the NPX group also had modest improvement in pain at rest and in 50-foot walk time. Sixty-two patients completed the 2-year study. Among these patients, radiographic progression was similar in the 2 treatment groups. Withdrawal from the trial due to lack of drug efficacy was slightly more frequent among patients in the ACT group (22% versus 16%), but withdrawal due to adverse drug effects was slightly more common in the NPX group (23% versus 18%).\n The efficacy of ACT treatment and NPX treatment was similar, although it was slightly better for NPX. The toxicity rate was slightly lower with ACT. However, the high rate of withdrawal in both treatment groups suggests that neither is satisfactory for the treatment of OA." ]

[ "9549449", "9424040", "16953857", "12648967", "21159080", "9458569", "18996423" ]

[ "The effects of postnatal health education for mothers on infant care and family planning practices in Nepal: a randomised controlled trial.", "Increasing immunization rates among inner-city, African American children. A randomized trial of case management.", "Postnatal home visiting for illicit drug-using mothers and their infants: a randomised controlled trial.", "Postnatal home visits in teenage mothers: a randomised controlled trial.", "Randomized controlled trial to improve childhood immunization adherence in rural Pakistan: redesigned immunization card and maternal education.", "Assessment of parent education methods for infant immunization.", "Redesigned immunization card and center-based education to reduce childhood immunization dropouts in urban Pakistan: a randomized controlled trial." ]

[ "To evaluate impact of postnatal health education for mothers on infant care and postnatal family planning practices in Nepal.\n Randomised controlled trial with community follow up at 3 and 6 months post partum by interview. Initial household survey of study areas to identify all pregnant women to facilitate follow up.\n Main maternity hospital in Kathmandu, Nepal. Follow up in urban Kathmandu and a periurban area southwest of the city.\n 540 mothers randomly allocated to one of four groups: health education immediately after birth and three months later (group A), at birth only (group B), at three months only (group C), or none (group D).\n Structured baseline household questionnaire; 20 minute, one to one health education at birth and three months later.\n Duration of exclusive breast feeding, appropriate immunisation of infant, knowledge of oral rehydration solution and need to continue breast feeding in diarrhoea, knowledge of infant signs suggesting pneumonia, uptake of postnatal family planning.\n Mothers in groups A and B (received health education at birth) were slightly more likely to use contraception at six months after birth compared with mothers in groups C and D (no health education at birth) (odds ratio 1.62, 95% confidence interval 1.06 to 2.5). There were no other significant differences between groups with regards to infant feeding, infant care, or immunisation.\n Our findings suggest that the recommended practice of individual health education for postnatal mothers in poor communities has no impact on infant feeding, care, or immunisation, although uptake of family planning may be slightly enhanced.", "Immunization rates in the inner city remain lower than in the general US population, but efforts to raise immunization levels in inner-city areas have been largely untested.\n To assess the effectiveness of case management in raising immunization levels among infants of inner-city, African American families.\n Randomized controlled trial with follow-up through 1 year of life.\n Low-income areas of inner-city Los Angeles, Calif.\n A representative sample of 419 African American infants and their families.\n In-depth assessment by case managers before infants were 6 weeks of age, with home visits 2 weeks prior to when immunizations were scheduled and additional follow-up visits as needed.\n Percentage of children with up-to-date immunizations at age 1 year, characteristics associated with improved immunization rates, and cost-effectiveness of case management intervention.\n A total of 365 newborns were followed up to age 1 year. Overall, the immunization completion for the case management group was 13.2 percentage points higher than the control group (63.8% vs 50.6%; P=.01). In a logistic model, the case management effect was limited to the 25% of the sample who reported 3 or fewer well-child visits (odds ratio, 3.43; 95% confidence interval, 1.26-9.35); for them, immunization levels increased by 28 percentage points. Although for the case management group intervention was not cost-effective ($12022 per additional child immunized), it was better ($4546) for the 25% of the sample identified retrospectively to have inadequate utilization of preventive health visits.\n A case management intervention in the first year of life was effective but not cost-effective at raising immunization levels in inner-city, African American infants. The intervention was demonstrated to be particularly effective for subpopulations that do not access well-child care; however, currently there are no means to identify these groups prospectively. For case management to be a useful tool to raise immunizations levels among high-risk populations, better methods of tracking and targeting, such as immunization registries, need to be developed.", "Postnatal home-visiting programs for illicit drug-using mothers have reported some success in reducing harms in some areas but there is a lack of data on their impact on breastfeeding and immunisation rates.\n To investigate the effect on breastfeeding, immunisation and parental drug use. The hypothesis was that the outcomes of the home-visiting group (HVG) would be superior to the control group (CG).\n One hundred and fifty-two illicit drug-using women were recruited at 35-40 weeks gestation from King Edward Memorial Hospital, Perth, Western Australia and randomised after delivery to the HVG or the CG. The HVG had eight home visits; the CG had telephone contact at two months and a home visit at six months. The HVG received education and support for parenting, breastfeeding and child development. This was not provided by the research midwives for the CG.\n The main drugs were heroin, amphetamines, cannabis and benzodiazepines. Immunisation rates were similar for each group. Median duration of breastfeeding for the HVG was eight weeks (95% CI, 3.8-12.2); for the CG ten weeks (95% CI, 7.3-12.7). Drug use was reduced during pregnancy but increased by six months post-partum in both groups. The retention rates were: HVG 93%; CG 86%.\n The hypothesis for this study was not supported. Long-term studies are urgently required to assess the effects of parental drug use on infant and child development.", "Teenage pregnancies are associated with negative socioeconomic effects. Our aim was to ascertain whether a postnatal home-visiting service for teenage mothers younger than age 18 years could reduce the frequency of adverse neonatal outcomes and improve knowledge of contraception, breastfeeding, and infant vaccination schedules in this parent group.\n We enrolled 139 adolescents, attending a teenage pregnancy clinic, in a randomised controlled trial. After completing an antenatal questionnaire designed to assess their knowledge of contraception, infant vaccination, and breastfeeding, we assigned participants to either receive five structured postnatal home visits by nurse-midwives (n=65) or not (n=71). Assessment interviews were done 6 months postpartum. Our primary endpoint was unadjusted difference in knowledge between groups, and incidence of predefined adverse neonatal outcomes. Analysis was by intention to treat.\n Three women withdrew before randomisation because of late fetal loss, 11 mothers withdrew because of adverse neonatal outcomes (adverse neonatal outcome was a primary endpoint, but resulted in withdrawal from the study for knowledge outcomes), and one left voluntarily. Follow-up data were, therefore, available for 124 teenagers. Postnatal home visits were associated with a reduction in adverse neonatal outcomes (intervention: 2; control: 9; relative risk 0.24, 95% CI 0.05-1.08), and a significant increase in contraception knowledge (mean difference 0.92, 95% CI 0.32-1.52). However, there was no significant increase in knowledge with respect to breastfeeding or infant vaccination schedules associated with the home visits.\n Postnatal home-visiting services by nurse-midwives reduce adverse neonatal events and improve contraception outcomes, but do not affect breastfeeding or infant vaccination knowledge or compliance.", "A substantial dropout from the first dose of diphtheria-tetanus-pertussis (DTP1) to the 3rd dose of DTP (DTP3) immunization has been recorded in Pakistan. We conducted a randomized controlled trial to assess the effects of providing a substantially redesigned immunization card, centre-based education, or both interventions together on DTP3 completion at six rural expanded programme on immunization (EPI) centres in Pakistan.\n Mother-child pairs were enrolled at DTP1 and randomized to four study groups: redesigned card, centre-based education, combined intervention and standard care. Each child was followed up for 90 days to record the dates of DTP2 and DTP3 visits. The study outcome was DTP3 completion by the end of follow-up period in each study group.\n We enrolled 378 mother-child pairs in redesigned card group, 376 in centre-based education group, 374 in combined intervention group and 378 in standard care group. By the end of follow-up, 39% of children in standard care group completed DTP3. Compared to this, a significantly higher proportion of children completed DTP3 in redesigned card group (66%) (crude risk ratio [RR] = 1.7; 95% CI = 1.5, 2.0), centre-based education group (61%) (RR = 1.5; 95% CI = 1.3, 1.8) and combined intervention group (67%) (RR = 1.7; 95% CI = 1.4, 2.0).\n Improved immunization card alone, education to mothers alone, or both together were all effective in increasing follow-up immunization visits. The study underscores the potential of study interventions' public health impact and necessitates their evaluation for complete EPI schedule at a large scale in the EPI system.\n © 2010 Blackwell Publishing Ltd.", "To assess whether a video about infant immunization could inform parents as well as human counselling (oral presentation).\n Core information for parents about infant immunization was identified and packaged in an instructional video and a scripted oral presentation. Volunteer prenatal classes were randomly assigned a video or oral presentation. Participants completed pre- and post-test questionnaires covering the same 16 items. Scores were compared for each question and as a group means, using Fisher's exact test, 2-sided.\n 227 subjects participated, including 102 men and 124 women. Groups were similar in terms of gender mix, parenting experience and recent reading about immunization. Pre-test knowledge scores were similarly low between groups. Post-test scores were much higher but did not differ significantly between groups.\n In a prenatal classroom setting, video and oral presentations were equally effective in conveying key information about infant immunization.", "In Pakistan during 2000-2004, about 11-13% of children who received the first dose of diphtheria-pertussis-tetanus (DPT1) failed to complete its third dose (DPT3). We assessed the effect of a redesigned immunization card and center-based education to mothers on DPT3 completion. We enrolled 1500 mother-child units at DPT1, randomized them to three intervention and one standard care groups, and recorded their DPT3 visits during a 90-day follow-up. In multivariable analysis, a significant increase of 31% (adjusted RR=1.31, 95% CI=1.18-1.46) in DPT3 completion was estimated in the group that received both redesigned card and center-based education compared with the standard care group." ]

[ "10431992", "8282745", "11174790" ]

[ "External femoral vein valvuloplasty with limited anterior plication (LAP): a 10-year randomized, follow-up study.", "Femoral vein valve repair with limited anterior plication (LAP).", "Does surgical correction of the superficial femoral vein valve change the course of varicose disease?" ]

[ "The aim of this study was to evaluate the effects after 10 years of external valvuloplasty of the femoral vein (limited anterior plication or LAP). After informed consent patients with venous hypertension due to deep and superficial venous incompetence were randomized into two treatment groups. Both groups were treated with superficial vein surgery (ligation and section of the major incompetent superficial veins). Group 2 was treated with the same procedure and with LAP. External valvuloplasty of the superficial femoral vein was performed with plication of the anterior vein wall after limited dissection of the vein. Results were evaluated with color-duplex scanning and ambulatory venous pressure (AVP) measurements. Endpoints were AVP, refilling time (RT), presence/absence of reflux at the superficial femoral vein, the variation in the diameter of the vein, and quality of life score (QLS). No complications were observed. All femoral veins treated with LAP were competent after 10 years. Significantly lower AVP and longer RT were observed in the LAP group. Also the average diameter of the vein was smaller in the LAP group. Moreover, QLS was significantly better in the LAP group after 10 years. In conclusion, in selected subjects, with moderate deep venous incompetence, functional cusps, or incompetence mainly due to relative enlargement of the femoral vein, LAP may be an effective alternative to external valvuloplasty.", "Limited anterior plication (LAP) of the incompetent femoral vein was used in 2 groups of subjects with venous hypertension due to deep and superficial venous incompetence. Group 1 subjects were treated only with superficial veins surgery while groups 2 was treated with external valvuloplasty (LAP) at the level of the incompetent femoral vein. The plication was performed at the anterior side of the vein after limited dissection and manipulation. During a two-year follow-up the results of LAP were evaluated with color-duplex and ambulatory venous pressure (AVP) measurements. Nine of the 11 femoral veins treated with LAP were competent after 2 years (in 2 the incompetence was reduced). A lower AVP and RT was found in subjects treated with LAP in comparison with those in Group 1. Also the number of recurrent varicose veins (incompetent venous sites) and the average diameter of the femoral vein were higher in Group 2 (superficial surgery only). As no complications were observed LAP can be considered an alternative to the standard external valvuloplasty in cases of moderate incompetence when valve cusps are present and functional and incompetence is mainly due to relative enlargement of the vein diameter.", "We tested the hypothesis that the course of primary chronic venous insufficiency can be changed by correction of the incompetent valve in the superficial femoral vein.\n This was a prospective, randomized, controlled study. A total of 125 extremities with reflux in greater saphenous and superficial femoral veins and belonging to clinical classes C2-C4 were analyzed. During the first 5 years, the type of clinical dynamics and changes in valvular function were determined in each patient. Patients were stratified according to the type of clinical dynamics and randomly assigned to treatment groups. Phlebectomy was performed in all extremities. In each of 64 extremities (the study group), the proximal incompetent superficial femoral vein valve was corrected as a part of the primary intervention. Patients were followed up for 7 to 8 years after surgery.\n The clinical dynamics of the extremity significantly depended on reflux changes. Increase in superficial femoral vein reflux was found in 74% of the extremities with progressive clinical dynamics but in only 47% of extremities with stable clinical dynamics (chi(2) = 9.71; P <.01). After surgical treatment, 65% of the extremities in the control group showed stable improvement; in 11%, recurrent varicosity was found; in 24%, the disease was aggravated. Of the extremities in the study group, 86% had stable improvement, 5% had recurrent varicosity, and 10% were aggravated (P <.05). Extremities with the progressive type of clinical dynamics were main contributors to this difference (chi(2) = 7.86; P <.05). In 92% of the extremities with corrected valves and in 50% of the extremities with increase in reflux after valvuloplasty, clinical improvement was observed (chi(2) = 11.5; P <.01). Extremities with corrected valvular function demonstrated superior results in comparison with extremities with stable valvular function in the control group (clinical improvement in 92% and 66% of extremities, respectively; P <.005).\n In patients with chronic venous insufficiency, two types of clinical dynamics, stable and progressive, can be identified. The progressive type is associated with the presence of superficial femoral vein reflux and increasing greater saphenous vein reflux. Superficial vein surgery neither corrects superficial femoral vein reflux nor prevents it from progressing further. Correction of a single superficial femoral vein valve during primary intervention significantly improves the long-term results of superficial venous surgery. This improvement is associated with the prevention of reflux progression. Surgical correction of the incompetent superficial femoral vein valve changes the course of primary chronic venous insufficiency." ]

[ "16850671", "8392274", "7705531", "16165135", "20149045", "2226910" ]

[ "Comparison of low-dose monophasic oral contraceptive pills and expectant management in treatment of functional ovarian cysts.", "Management of functional ovarian cysts after induction of ovulation. A randomized prospective study.", "Expectant management of functional ovarian cysts: an alternative to hormonal therapy.", "Diagnosis and management of simple ovarian cysts.", "Treatment of clomiphene citrate-related ovarian cysts in a prospective randomized study. A single center experience.", "Hormonal treatment of functional ovarian cysts: a randomized, prospective study." ]

[ "To compare the effectiveness of low-dose monophasic oral contraceptive pills in the treatment of spontaneously occurring functional ovarian cyst detected by ultrasonography compared with expectant management.\n A total of 70 women in their reproductive period with functional ovarian cysts detected by means of ultrasonography were randomized to low-dose monophasic Oral Contraceptive pills (OC) or to expectant management and followed up at one month with a second ultrasonography. If the ovarian cysts were still present, the women were followed for another month while on the same treatment.\n At the first month, the remission rates of ovarian cyst were 63.6% in low-dose monophasic OC and 52.9% in expectant groups. At the second month, the cumulative remission rates increased up to 72.7% in low-dose monophasic OC and 67.6% in expectant groups. There was no statistically significant difference between the two groups at both the first and second month of treatment. The most common side effect in women using OC was acne (18%).\n Low-dose monophasic OC were no more effective than expectant management in the treatment of spontaneously occurring functional ovarian cysts.", "To investigate the need for hormonal treatment in patients with functional ovarian cysts after induction of ovulation, a randomized prospective study was performed. Fifty-four patients who were found to have ovarian cysts after induction of ovulation were randomly assigned to two groups: a) Treatment with estrogen/progesterone. b) Expectant management. The main outcome measure was resolution of ovarian cysts. There was no significant difference between the groups. We conclude that hormonal treatment is not necessary in cases with functional ovarian cysts after induction of ovulation.", "We studied whether the administration of oral contraceptives facilitates the disappearance of spontaneously formed functional ovarian cysts.\n Eighty patients in whom ultrasonography revealed unilateral, mobile, unilocular, thin-walled ovarian cysts without internal echoes and greater than 30 mm but not exceeding 60 mm in diameter were enrolled into the study. Patients were randomized by stratification to receive a low-dose monophasic pill, a high-dose monophasic pill, a multiphasic pill or no therapy. Patients were re-evaluated after 5 weeks of therapy and at the end of therapy (10 weeks).\n The mean ages and the mean cyst diameters of the patients for each group were not significantly different. We did not find a significant effect of oral contraceptive administration on the disappearance rate of functional ovarian cysts over that of expectant management.\n We conclude that oral contraceptive therapy even with multiphasic pills is very effective in the management of functional ovarian cysts but expectant management achieves similar success rates and may be a good alternative to oral contraceptive therapy.", "nan", "The present study aims to compare the effectiveness of placebo, low dose and very low dose oral contraceptives (OC) in the treatment of clomiphene citrate (CC)-related ovarian cysts.\n A prospective randomized placebo controlled study was undertaken at the Infertility Department of Dr. Zekai Tahir Burak Women's Health Education and Research Hospital. A total of 3250 primary infertile patients were administered CC for ovulation induction because of ovulatory dysfunction and/or unexplained infertility. One hundred and eighty-six women who were diagnosed with CC-related ovarian cysts greater than 20 mm on the third day of the following menstrual cycle, were eligible for the study. Group 1 (n = 62) was treated with very low dose OC (100 microg levonorgestrel + 20 microg ethinyl estradiol [EE]), group 2 (n = 62) with low dose OC (150 microg desogestrel + 30 microg EE) and group 3 (n = 62) with a placebo. The first control was 4 weeks later. Women with persistent cysts (n = 57) were called in 4 weeks later to continue the same treatment.\n Demographic data were similar among the groups. At the first month, the regression rates of ovarian cysts were 64.5, 61.3 and 66.1% in groups 1, 2 and 3, respectively (P = 0.849). Among the 57 women (20, 19 and 18 from groups 1, 2 and 3, respectively) with persistent cysts, the regression rates were 65.0, 63.2 and 55.6%, respectively at the second month (P = 0.821). Persistence of ovarian cysts was significantly higher in women with a longer duration of CC treatment than in women with a shorter duration (P < 0.001).\n Any treatment might be appropriate for patients with a CC-related ovarian cyst. However, there is no evidence to administer OC for treating CC-related ovarian cysts. Expectant management may also achieve similar success rates.", "Estrogen (E)/progestin therapy for functional ovarian cysts is widely used in clinical practice, but the efficacy of this treatment has not been determined in controlled trials. In this study, we examined the effect of E/progestin administration in a group of infertility patients enrolled in a program of ovulation induction who had cysts identified by transvaginal sonography. Patients were randomized to receive either norethindrone 1 mg/mestranol 0.05 mg/d (group A, n = 24) or no treatment (group B, n = 24) for up to 6 weeks. Patients were re-evaluated by sonography at 3, 6, and 9 weeks after entry into the protocol. The ages, mean cyst diameters, and proportions of patients having received gonadotropins in the previous menstrual cycle were not significantly different among the two groups. All patients who had a sonographic abnormality persisting for 9 weeks were surgically explored and found to have pathological cysts. The rate of disappearance of functional ovarian cysts was not affected by E/progestin treatment." ]

[ "15005784", "6428627" ]

[ "Episiotomy and perineal tears presumed to be imminent: randomized controlled trial.", "Is routine episiotomy necessary?" ]

[ "The indication of the restricted use of episiotomy at tears presumed to be imminent is not clear.\n Randomized controlled trial with two perineal management policies. Use of episiotomy: (a). only for fetal indications and (b). in addition at a tear presumed to be imminent. Participants: 146 primiparous women with an uncomplicated singleton pregnancy at >34 weeks of gestation. For the intention-to-treat analysis those 109 women were included who vaginally delivered a live full-term baby between January 1999 and September 2000: 49 women in group a, 60 in group b.\n Reduction of episiotomies, increase of intact perinea or only minor perineal trauma (intact perineum and first-degree tears), third-degree tears, anterior perineal trauma, perineal pain in the postpartum period, pH of the umbilical artery, Apgar scores, maternal blood loss.\n Episiotomy rates were 41% in group a and 77% in group b (p < 0.001). Women in the restrictive policy group had a greater chance of an intact perineum (29% vs. 10%; p = 0.023) or only minor perineal trauma (39% vs. 13%; p = 0.003) and had significant lower pain scores postpartum at different activities. There were no statistically significant differences with regard to third-degree tears, anterior trauma, pre- and postpartum hemoglobin concentrations, Apgar scores and pH of the umbilical artery.\n Avoiding episiotomy at tears presumed to be imminent increases the rate of intact perinea and the rate of only minor perineal trauma, reduces postpartum perineal pain and does not have any adverse effects on maternal or fetal morbidity.", "One hundred and eighty one primigravid women delivering vaginally in July and August 1982 in the Rotunda Hospital, Dublin, were randomly allocated to one of two groups. Patients in one group were to undergo episiotomy. Those in the other group were not to undergo episiotomy unless it was considered to be essential. The outcome was compared with that of the clinical practice over the previous six months at the hospital. Of the 92 patients allocated not to undergo episiotomy, seven (8%) had one done for medical reasons compared with 507 (89%) in the previous six months. First degree tears occurred in 23 (25%) and second degree tears in 43 (47%). Nineteen (21%), however, retained an intact perineum compared with only 35 (6%) of the women who had delivered in the preceding six months. Assessments of perineal pain, bruising, swelling, and healing and records of ingestion of analgesics were made for the first four days after delivery, and again at a check up six weeks after delivery, in patients who had had spontaneous vertex deliveries. Forty patients who underwent episiotomy and 37 who sustained a second degree tear formed two comparable groups. There was no difference in outcome between them. Data were also evaluated for 19 women who retained an intact perineum, 22 who sustained a first degree tear, and 11 who underwent episiotomy and epidural anaesthesia; all 52 of these women had spontaneous vertex deliveries. Despite severe soft tissue injury in two patients those who fared best were those who retained an intact perineum. First degree tears were associated with symptoms similar to those associated with second degree tears. Those who fared worst were women who underwent episiotomy after epidural anaesthesia. The value of routine episiotomy in primigravid patients is questioned, but the final decision can be made only by the accoucheur at the time of imminent delivery." ]

[ "10770301" ]

[ "Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study Group. Heparin in Acute Embolic Stroke Trial." ]

[ "Patients with acute ischaemic stroke and atrial fibrillation have an increased risk of early stroke recurrence, and anticoagulant treatment with heparins has been widely advocated, despite missing data on the balance of risk and benefit.\n Heparin in Acute Embolic Stroke Trial (HAEST) was a multicentre, randomised, double-blind, and double-dummy trial on the effect of low-molecular-weight heparin (LMWH, dalteparin 100 IU/kg subcutaneously twice a day) or aspirin (160 mg every day) for the treatment of 449 patients with acute ischaemic stroke and atrial fibrillation. The primary aim was to test whether treatment with LMWH, started within 30 h of stroke onset, is superior to aspirin for the prevention of recurrent stroke during the first 14 days.\n The frequency of recurrent ischaemic stroke during the first 14 days was 19/244 (8.5%) in dalteparin-allocated patients versus 17/225 (7.5%) in aspirin-allocated patients (odds ratio=1.13, 95% CI 0.57-2.24). The secondary events during the first 14 days also revealed no benefit of dalteparin compared with aspirin: symptomatic cerebral haemorrhage 6/224 versus 4/225; symptomatic and asymptomatic cerebral haemorrhage 26/224 versus 32/225; progression of symptoms within the first 48 hours 24/224 versus 17/225; and death 21/224 versus 16/225. There were no significant differences in functional outcome or death at 14 days or 3 months.\n The present data do not provide any evidence that LMWH is superior to aspirin for the treatment of acute ischaemic stroke in patients with atrial fibrillation. However, the study could not exclude the possibility of smaller, but still worthwhile, effects of either of the trial drugs." ]

[ "9085056", "7562171", "11513787", "12495099", "10475656", "11423598", "9001874", "10028739", "9619927", "9091940", "2327922", "10659898", "9521392", "10583283", "1547183", "10817324", "9503298", "15116826", "15330033", "8972416", "11417282", "15327447", "7880207", "8242939", "1402941", "9180311", "8659967", "9560497", "19219780" ]

[ "Double gloving as self protection in abdominal surgery.", "A prospective study of the efficacy of various gloving techniques in the application of Erich arch bars.", "How often does glove perforation occur in surgery? Comparison between single gloves and a double-gloving system.", "Randomised controlled trial of glove perforation in single and double-gloving methods in gynaecologic surgery.", "Double gloving and a system for identifying glove perforations in maxillofacial trauma surgery.", "Intraoperative glove perforation--single versus double gloving in protection against skin contamination.", "Efficacy of double gloving with a coloured inner pair for immediate detection of operative glove perforations.", "Double gloving and a glove perforation indication system during the dental treatment of HIV-positive patients: are they necessary?", "The protective effect of a cut-resistant glove liner. A prospective, randomised trial.", "Does double gloving protect surgical staff from skin contamination during plastic surgery?", "Efficacy of double versus single gloving in protecting the operating team.", "Perforation in single- and double-gloving methods for cesarean section.", "Comparison of perforation between single and double-gloving in perineorrhaphy after vaginal delivery: a randomized controlled trial.", "Electronic evaluation of the value of double gloving.", "The effectiveness of double-gloving in obstetrics and gynaecology.", "Incidence of glove perforations in gastrointestinal surgery and the protective effect of double gloves: a prospective, randomised controlled study.", "Outer gloves in orthopaedic procedures: a polyester/stainless steel wire weave glove liner compared with latex.", "Glove perforations in open and laparoscopic abdominal surgery: the feasibility of double gloving.", "Glove perforation in orthopaedic and trauma surgery. A comparison between single, double indicator gloving and double gloving with two regular gloves.", "Perforation rate using a single pair of orthopedic gloves vs. a double pair of gloves in obstetric cases.", "Glove perforation rate in vascular surgery--a comparison between single and double gloving.", "Randomized controlled trial of glove perforation in single- and double-gloving in episiotomy repair after vaginal delivery.", "Prevalence and prevention of glove perforation during cardiac operations.", "Intraoperative glove perforation. A comparative analysis.", "Control of contamination of the operative team in total joint arthroplasty.", "Increased awareness of glove perforation in major joint replacement. A prospective, randomised study of Regent Biogel Reveal gloves.", "Subjective effects of double gloves on surgical performance.", "A randomized controlled trial of double-versus single-gloving in vascular surgery.", "Knitted outer gloves in primary hip and knee arthroplasty." ]

[ "To investigate if double gloving can reduce the rate of perforation of glove barriers during abdominal surgery.\n Randomised controlled trial.\n County hospital, Denmark.\n 400 glove barriers from principal surgeons and first assistants used at consecutive abdominal operations.\n Each participant was randomised to wear either a pair of single or double gloves.\n The number of perforated glove barriers in the two study groups.\n 40 single glove barriers perforated (20%) and in 8 of the double glove group both gloves perforated (4%) (p < 0.001). Glove barriers on non-dominant hands were more often perforated than those on dominant hands, and both the duration of the operation and the seniority of the doctor were associated with increased rates of perforation.\n Double gloving reduces the rate of perforation of glove barriers during abdominal surgery and thereby the number of episodes in which transmission of disease from patient to surgeon would be possible.", "This is a prospective study of the efficacy of three different techniques of triple gloving during the application of Erich arch bars. Two different cut-resistant glove liners and three layers of latex gloves were compared with double gloving.\n Thirty patients underwent Erich arch bar placement from first molar bilaterally on both arches. Two surgeons per case were arbitrarily placed into one of four groups that included double latex gloving, triple gloving with kevlar or stainless steel glove liners, or triple layer latex gloving, based on the availability of glove liners. All gloves were collected postoperatively and tested for perforation using water insufflation.\n One hundred eight of 120 outer gloves were perforated. There were 16 perforations in 11 inner gloves of the double latex glove group, but no perforations in the inner gloves of the triple latex glove group. There were two inner gloves with one perforation each in the stainless steel group and one glove with a perforation in the kevlar group. All techniques of triple gloving were found to be superior to double gloving. There was no difference between the techniques of triple gloving.\n During certain high-risk procedures greater protection to the surgeon can be obtained by triple gloving. The use of cut-resistant glove liners or triple layer latex gloving is superior to double layer latex gloving.", "In surgery, intact gloves protect the surgeon from bloodborne pathogens and the surgical wound from microorganisms on the skin of the surgeon. However, glove perforation is very common, and puncture rates as high as 61% are published in the literature. One objective of this study was to compare puncture rates between a unique double-gloving puncture indication system and single-use gloves, and another was to determine the extent to which glove perforations remain undetected during surgery.\n The study material comprised all gloves used in surgical operations at our hospital for a period of 2 months. The analysis was made by the glove type in a prospective and randomized manner. Gloves were tested immediately after the surgical procedure using the approved standardized water-leak method for 2 minutes to detect any holes. The gloves used in this study were either a double-gloving puncture indication system or the standard glove used at our hospital.\n In 885 operations altogether, 2,462 gloves were tested; 1,020 single gloves, 1,148 double-glove systems, and 294 combination gloves were studied. The overall perforation rate was 192 out of 2,462 gloves (7.80%), and 162 out of 885 operations (18.3%). The detection of perforation during surgery was 28 out of 76 (36.84%) with single gloves, 77 out of 89 with the double-gloving system (86.52%), and 9 out of 27 with combination gloves (33.33%; P <0.001). The inner glove of the double-gloving system was punctured in 6 out of 88 outer glove perforations (6.82%).\n In view of the critical importance of safety at work by having a sterile barrier between surgeon and patient, it is very important to use a double-gloving puncture indication system, at least in operations where there is a high risk of glove perforation.", "To assess the value of double-gloving in gynaecological surgery.\n A prospective randomised controlled trial of glove perforation in single- and double-gloving methods.\n Rajavithi Hospital between 1 September 1999 to 31 August 2000.\n Eighty-eight (88) and 82 primary surgeons were selected at random to make up single- and double-gloving groups, respectively, while performing total abdominal hysterectomy (TAH) with or without bilateral salpingo-oophorectomy (BSO).\n The gloves were tested by immersion in water.\n The glove perforation rate was 6.09% and 22.73% in double-inner and single gloves, respectively, with this difference being statistically different (p < 0.05). There was no significant difference between the glove perforation rates in single gloves (22.73%) and in double-outer gloves (19.51%). There was matched perforation of the same finger of both outer and inner gloves in 1.22% of total double-inner gloves.\n The double-gloving methods significantly reduced the risk of surgeons' hands contacting blood, when compared with the single-gloving method, in TAH with/or without BSO.", "The treatment of some maxillofacial fractures has an incidence of glove perforation as high as 50%, with over 80% going unnoticed at the time of operation. We investigated double gloving and a glove perforation indication system to ascertain whether the latter offered any additional protection. 1061 gloves used for 113 patients were examined. The outer glove perforation rate was significantly higher than the inner glove (0.48 compared with 0.10, P < 0.0001). There were fewer unnoticed perforations in the glove perforation indication group than the standard surgical glove group (19% compared with 79%, P < 0.0001). The indication system was most effective in wet operating fields. The perforation rate varied with the type of fracture and treatment. Mandibular fractures that were 'hand-held', while bone-plated had a lower mean number of outer glove perforations/operation than fractures treated with temporary intermaxillary fixation (0.43 compared with 4.62, P < 0.0001).", "Surgeons have the highest risk of contact with patients' blood and body fluids, and breaches in gloving material may expose operating room staff to risk of infections. This prospective randomised study was done to assess the effectiveness of the practice of double gloving compared with single gloving in decreasing finger contamination during surgery. In 66 consecutive surgical procedures studied, preoperative skin abrasions were detected on the hands of 17.4% of the surgeons. In the double gloving pattern, 32 glove perforations were observed, of which 22 were in the outer glove and 10 in the inner glove. Only four outer glove perforations had matching inner glove perforations, thus indicating that in 82% of cases when the outer glove is perforated the inner glove will protect the surgeon's hand from contamination. The presence of visible skin contamination was also higher in perforation with the single gloving pattern (42.1%) than with the double gloving pattern (22.7%). An overwhelming majority of glove perforations (83.3%) went unnoticed. Double gloving was accepted by the majority of surgeons, especially with repeated use. It is recommended that double gloves are used routinely in all surgical procedures in view of the significantly higher protection it provides.", "To compare the efficacy of double gloving with an inner coloured pair of gloves and double gloving with classic gloves, for prompt detection of perforation during a single standard operation.\n Prospective, randomised study.\n Teaching hospital, France.\n 100 Consecutive patients with haematological malignancy or AIDS, who were referred for implantation of a vascular access port.\n Insertion of a central line with an implantable chamber under local anaesthesia. The use of double gloving with an inner coloured pair or with classic gloves was decided preoperatively by random allocation.\n Visual detection of one or more perforations on one or more gloves during operation, localisation of the perforation(s), and post-operative evaluation of the water tightness of the gloves.\n There were a total of 14 perforations of the outer gloves, 9 were detected during operation in the coloured inner pair group compared with none in the standard gloves group. Postoperative testing showed that there were no undetected perforations in the coloured inner pair group compared with 5 in the standard gloves group.\n Double gloving with a coloured inner pair is effective in the peroperative detection of accidental perforations in surgical gloves.", "The aim of this study was to compare the incidence of glove perforation when double gloved or single gloved during the routine treatment of HIV-positive patients. In addition, a glove perforation indication system based on a double gloving technique was assessed.\n Prospective, randomised and open study of glove perforation.\n 138 consecutive HIV-positive patients underwent routine dental treatment by senior dental staff and dental hygienists in a teaching hospital. Staff wore either single gloves (Regent Biogel D or standard surgical gloves) or double gloves (Regent 'Reveal' perforation indication system or standard surgical gloves). A subjective assessment of glove comfort, sensitivity and ease of donning was made using a visual analogue scale.\n The incidence of glove perforation/procedure was low, 2.9%. There were no skin penetrating injuries, visible exposure to body fluids or unnoticed perforations. Double gloving was subjectively less comfortable and sensitive than single gloving (P < 0.0001). The glove perforation indication system did not increase the detection of intra-operative perforations.\n There is unlikely to be any significant benefit from the use of a double gloving technique or perforation indication system during the routine dental treatment of HIV-positive patients.", "We performed a prospective, randomised study comparing the rates of glove perforation using double latex gloving with or without a disposable protective glove liner (Paraderm) on 118 patients undergoing primary or revision arthroplasty of the hip or knee by one surgeon (FRH). The patients were randomly allocated into two groups: in group 1 an inner and outer pair of latex gloves were worn as double gloves and in group 2 the glove liner was worn between the two latex gloves. There was glove perforation in at least one outer glove in 99 operations (84%). The operating surgeon was aware of the perforation in 21 of these. There were 22 perforations of the inner glove. Group 1 had a significantly higher perforation rate per operation (p < 0.05) than group 2. Our findings show that protective glove liners significantly reduce the rate of perforation of the inner glove during hip and knee arthroplasty.", "In a randomized study, the effectiveness of double gloving in maintaining an intact barrier between the patient and the hands of the surgical staff during plastic surgery operations was tested. For 2 months, the surgical staff of a plastic surgery unit randomly wore single or double gloves during all elective surgical procedures. At the end of the operations, the gloves were tested by the water filling test. A total of 1092 gloves were examined. Twelve accidental injuries were noticed during the operations, and 67 unnoticed perforations occurred. The data suggest that the risk of perforation and exposure increases with the length and complexity of the procedures. It was concluded that double gloving is effective in plastic surgery, inasmuch as the barrier protection was maintained by the inner glove in two of three cases in which the outer glove was perforated inadvertently. Plastic surgeons must balance the improved security of double gloving with the possible discomfort or reduced sensitivity.", "Double-glove perforation rates and perforation rates in standard single-gloved operating teams were compared, in order to determine whether double gloving provides additional protection for the operating team. Patients were randomized to undergo surgery with a double-gloved or single-gloved operating team. All gloves worn during the operation were tested for perforations by water-filling and individual digital distension; 115 single-gloved operations and 103 double-gloved operations were performed. There were 841 individual operating team members 'at risk'. In the single-glove group, 20.8% of individuals had perforations, but only 2.5% had perforations in both inner and outer gloves (dual perforation) in the double-glove group (P less than 0.0001). The surgeon was most at risk of glove perforation (34.7% of cases in the single-glove group, 3.8% dual perforation in the double-glove group). Longer operations were associated with increased risk of glove perforation. Double-gloving significantly reduces the risk of skin contamination by blood and body fluids and is recommended for all high risk cases.", "To compare glove perforation between the single- and double-gloving method in cesarean section.\n Three hundred primary surgeons selected at random to be two equal groups--single and double gloving in cesarean section--at Rajavithi Hospital from 1 November 1997 to 31 March 1998. The gloves were tested by immersing in water. The level of statistical significance was noted at P < 0.05.\n The prevalence of glove perforation was 10.67% and 2% in single- and double-inner glove, respectively, with significant difference.\n The double-gloving method had a significant benefit in protecting the primary surgeons' hands from exposure to blood compared with the single-gloving method in cesarean section.", "A prospective randomized controlled trial of single and double-gloving methods in perineorrhaphy after vaginal delivery was performed between August 1, and September 30, 1996 at Rajavithi Hospital to compare glove perforation between both methods. We examined 1,316 individual gloves in the double-gloving method and 742 individual gloves in the single-gloving method. These gloves were tested by immersing in water. The glove perforation rate was 5.2% (107 of 2,058). There was significant reduction in the glove perforation rate of double-inner gloves (2.7%) compared with the single-gloving group (6.7%). The perforation rate of the double outer-gloves group was 5.9%. The perforation rate in the matched outer and inner perforation was found only in 0.3% (2 of 658). The double-gloving method had a significant benefit in protection of the surgeon's hand from the exposure to blood compared with the single-gloving method.", "Breakdown of the surgeon-patient barrier represents a risk for transmission of infectious disease. Such breakdowns are frequently not recognized by the surgical team. The protection afforded by double gloving under normal operating conditions was evaluated.\n An electronic device detected breakdown of the surgeon-patient barrier in a series of 80 surgical procedures, randomly assigned to either double or single gloving. Fluid contact due to glove perforation, porosity or gown wetting was recorded during 151 individual surgeon episodes covering 238 operator-hours. Surgical procedures were called superficial for incisions of less than 10 cm.\n Double gloving reduced the number of perforation and porosity alarms twofold in both superficial and deep surgical procedures. Deep procedures carried a sevenfold increased risk of barrier breakdown compared with superficial procedures, the risk being greatest for the principal operator.\n Without electronic detection, a large majority of barrier breakdowns would remain undetected by the surgical team and lead to prolonged contact with potentially contaminating body fluids. The use of double gloving provides real protection against such contamination risks.", "nan", "To investigate the incidence of glove perforations during various types of gastrointestinal surgery, to record the incidence of blood contamination of the hands, and to evaluate the protective effect of double gloving.\n Randomised prospective trial.\n University hospital, Denmark.\n 566 pairs of gloves tested on surgeons, assistants, and scrub nurses.\n The participants were allocated to wear either single gloves or Indicator double gloves.\n The number of glove perforations and the incidence of blood contamination of the hands.\n The perforation rate in single gloves was 53/306 (17%), and that of both outer and inner Indicator gloves at corresponding sites was 6/260 (2%) (p < 0.0001). Double gloving reduced the rate of blood contamination of the hands among surgeons from 15/115 (13%) to 2/98 (2%) (p < 0.005).\n The use of Indicator double gloves is recommended in gastrointestinal surgery because of the appreciable protection against blood contamination that they offer.", "To compare the efficacy of traditional double latex gloving with that of a highly cut-resistant polyester/stainless steel wire weave glove (PSSWWG) over a single latex inner glove for the prevention of perforation of the inner latex glove.\n The primary surgeon and first assistant were involved in a prospective randomized study. Group I consisted of twenty-five procedures in which double latex gloves were used. Group II consisted of twenty-five procedures in which a PSSWWG liner was worn over an inner latex glove. All inner gloves were tested for perforations; all gloves exchanged that were presumed to have a perforation were noted and also tested. The type and length of the procedure were recorded. The dominant hand was recorded for all participants, along with their comments on the PSSWWG liner's performance.\n Orthopaedic Trauma Service, Hospital for Special Surgery. New York.\n Major operative cases, November 1996 to February 1997.\n Inner latex glove perforations.\n With the use of PSSWWG liners, the percentage of inner gloves found with a perforation dropped from 19 percent in the double latex group to 15 percent in the PSSWWG liner group (not statistically significant, p = 0.4). Two thirds of the perforations were in the primary surgeon's gloves, located in either the index finger or thumb. Nearly 80 percent of all perforations went unrecognized in both groups. Ninety-five percent of all perforations were in gloves that had been in use for more than 120 minutes (statistically significant, p = 0.01).\n The particular cut-resistant glove studied (Sceptor) did not significantly reduce the rate of inner glove perforations. Other studies with different cut-resistant glove types and protocols have proven the liners effective. We would still recommend using outer cloth or cut-resistant type gloves when bone fragments are being manipulated or when using sharp implants or saws. At a minimum, surgical gloves should be changed every two hours.", "According to the traditional view, the glove protects the patient from the bacterial growth of the surgeons' hands and doing so prevents infections. Today, with growing incidences of HIV and Hepatitis B and C, surgical gloves are also important as protection for the surgeon. We compared the safety of double indicator gloves to standard single surgical gloves by investigating how often surgical gloves are punctured in laparoscopic and open gastrointestinal surgery.\n As study material we gathered all gloves that had been used in gastrointestinal surgery in Satakunta Central Hospital during two months. 814 gloves from 274 operations were tested by using standardized water filling test method.\n In open surgery 67 gloves out of 694 had been punctured (9.6 percent). Puncture occurred in 22.5 percent of operations (53 out of 236). During open surgery 24 holes out of 35 were undetected with single gloves (69 percent). With double indicator gloves, only 3 out of 31 holes were unnoticed (10 percent). Long duration of operation increased the risk of puncture. In laparoscopic operations 4 gloves out of 120 had been perforated (3.3 percent).\n Double surgical gloves give markedly better protection in surgery. This is important especially in high risk operations.", "The spread of viral diseases such as HIV has highlighted the importance of protecting medical personnel against contamination from blood. We have assessed the frequency of the perforation of surgical gloves during orthopaedic and trauma surgery and compared the efficiency of single and double gloving. We examined all the gloves used by surgeons for a period of two months. There were 1769 gloves from 349 operations. Perforations occurred in 18.5% of conventional and 5.8% of arthroscopic procedures. The risk of contamination from blood was 13 times higher when using single compared with double gloves. Surprisingly, the combination of two regular gloves was much less efficient than double indicator gloves when comparing the rate of perforation of the inner glove when the outer had been damaged (24% vs 4.9%; p = 0.02). We recommend double gloving in orthopaedic surgery in general and also in long arthroscopic procedures.", "Our purpose was to determine the perforation rate for a single pair of orthopedic gloves vs. a double pair of regular gloves in obstetric cases. Faculty, residents, medical students, and surgical technicians were assigned randomly to use either double gloves or single orthopedic gloves. After each procedure, the gloves were examined by filling with water, occluding the cuff, and observing for streams of water. The perforation rate for the double gloves (both inner and outer glove at the same location) was 7% (12/169), similar to the 7% (12/172) for single orthopedic gloves (P < 0.9). After adjusting for procedure type there was no association between the type of gloves and perforation rate. Fifty-four percent of all perforations were not recognized intraoperatively. Of those individuals with glove perforations, 4/24 (17%) observed blood on the hand at the end of the procedure. Double-gloved users complained more frequently than single-gloved users of loss of dexterity (77/169, 46%, 95% CI 38-53%) vs. (6/172, 3.5%, 95% CI 0.7-6%) (P < 0.001) and numbness (12/169, 7%, 95% CI 3.2-11%) vs (1/172 0.6%, 95% CI 0.55-1.7%) (P < 0.005). Although the use of a single pair of orthopedic gloves is more costly than a double pair of regular gloves ($78 vs. $15 per box), it is as safe and as effective as a double pair of gloves in maintaining a sterile barrier. The primary advantage of a single pair of orthopedic gloves is that surgical dexterity is minimally compromised when compared to double gloves.", "In surgery intact gloves act as a sterile barrier between surgeon and patient. The impermeable gloves protect the surgeon from bloodborne pathogens such as HIV, hepatitis B, and hepatitis C. On the other hand, the surgical wound is protected from micro-organisms from the skin of the surgeon. One objective of this study was to compare puncture rates between the double gloving color indication system and single-use gloves and the other to determine the extent to which glove perforations remain undetected during the course of vascular surgical operations.\n The study material comprised all gloves used in vascular surgical operations at Satakunta Central Hospital for a period of two months. The analysis was made by the glove type in a prospective and randomised manner. Gloves were tested immediately after the surgical procedure using the approved standardized water-leak method. With this method the glove is filled with water using a special filling tube, and the water-filled glove is then checked for two minutes to detect any holes. The gloves used in this study were either double gloves with indicator, or the standard glove used at our hospital.\n In 73 operations altogether 200 gloves were tested, half of them were double gloves and half were single gloves. The perforation occurred in the double gloves 3 times and with single gloves 12 times. The overall perforation rate was 15 out of 200 gloves (7.5%). The detection of perforation during surgery was 60%. Most frequently the perforation was located in the second finger of the left hand, 9 out of 15 perforations.\n In view of the critical importance of safety at work both transmitting the pathogens from the skin of the surgeon to the wound and transmitting the bloodborne pathogens from the patient to the surgeon, it is very important to use double gloving at least in operations where there is a high risk of glove perforation.", "The aims of the study presented here were to compare the rate of glove perforation between single-gloving and double-gloving methods, and the time of operation and level of surgeon in episiotomy repair after vaginal delivery.\n A prospective randomized controlled trial was performed from the beginning of May to the end of December, 2002 at Ramathibodi Hospital. A comparison of glove perforation between single-gloving and double-gloving methods was performed. Glove perforations were tested by filling each glove with water. Glove perforation rate, position of perforation, time of operation and surgeon level of experience were analyzed.\n One hundred and fifty sets of double-gloving method and 150 sets of single-gloving method were evaluated. The glove perforation rates were 4.6 and 18% in double-inner gloves and single-gloves, respectively, with statistical difference (P < 0.05). There was no significant difference between glove perforation rates in double-outer gloves (22.6%) and single-gloves (18%). There was matched perforation of the same finger of both outer and inner gloves in 2% of all double-inner gloves. The frequency of glove perforation was classified by the surgeon's level of experience and time of operation was no difference in each level.\n The double-gloving method significantly reduced the risk of exposure of the surgeon's hand to the patient's blood, when compared with the single-gloving method in episiotomy repair. There were no differences in the rate of glove perforations compared to the time of operation and level of surgeon.", "nan", "A prospective study was conducted to determine the rate of puncture of the inner glove when various double-gloving protocols were used for elective total joint procedures. Group 1 consisted of 22 cases in which two pairs of regular latex gloves were used. Group 2 consisted of 25 cases in which outer \"orthopaedic\" gloves were used over regular latex gloves. Group 3 consisted of 24 cases in which Repel gloves were used between two regular latex gloves. The patients were randomly assigned to one of the three groups. All gloves, both inner and outer, were tested for holes at the end of the procedure. All gloves that were changed for presumed intraoperative holes were also tested. The type and duration of the procedure was also documented. Of the inner holes, there were significant differences between each group. Group 1 (double latex) and Group 2 (outer orthopaedic/inner regular) had significantly more holes than Group 3 (Repel between two regular gloves). There were no holes in Group 3, and Group 2 offered significant protection over Group 1.", "Reports of percutaneous transmission of blood-borne disease emphasize the need for control of intraoperative contamination. In a randomized prospective study, surgeons and surgical assistants involved in total hip and total knee arthroplasty adopted the following protocol: total body exhaust with hood, aspirator, knee-length impermeable gowns, foot covers, including knee-high covers and waterproof covers, and one of three combinations of gloving protocols: latex/latex changed hourly, latex/cloth, or latex/cloth/latex. All inner gloves were tested by a leak test. All needles and sharp instruments were passed on trays, and all contaminations and perforations were recorded. Each surgeon and assistant was inspected twice for contamination. There were no needle sticks, and only one of 267 personnel had head, neck, body, leg, or foot contamination. Perforation rates of inner gloves were 9.2% for latex/latex, 7.9% for latex/cloth, and 4.3% for latex/cloth/latex.", "An intact barrier between the hands of the surgeon and the patient remains the single most important factor in protection against infection for both. Increasing the awareness of possible glove perforation without skin penetration will decrease the risk of contamination. We performed a prospective, randomised trial comparing the incidence of glove perforation using a new type of glove (Regent Biogel Reveal) and standard double-gloves in total hip and knee replacement. One or more perforations was detected in 14.6% of all gloves. The new gloves increased significantly the awareness of perforation. Multiple perforations at the base of the ring finger were found in surgeons who wore wedding rings during the operation and we recommend that rings be removed before undertaking surgery.", "This randomised trial compared single gloves with combinations of double gloves to determine the subjective effects on comfort, sensitivity and dexterity in 32 surgeons. Glove perforation rates were also compared. Single gloves of the surgeon's normal size (method A) were used as control. Double gloves were worn in three different ways, selected randomly: normal gloves inside and gloves one-half size larger outside (method B); the larger gloves inside and the normal gloves outside (method C); and lastly, two pairs of gloves of normal size (method D). Double gloves by all three methods significantly protected against needle perforation of the inner gloves when compared with single gloves, but also significantly impaired comfort, sensitivity and dexterity. When the three types of double gloving were compared, there appeared to be advantages for method C for all modalities, but the differences did not reach statistical significance; also, more surgeons expressed a preference for method C. Perforation of the inner gloves was significantly less for double gloves than for single gloves. We conclude that double gloves often protect the surgeon against needle perforations, but are felt to impair comfort, sensitivity and dexterity.", "With the increasing incidence of hepatitis B and HIV, and the increasing awareness of the risk and prevalence of hepatitis C, it is becoming even more necessary to adopt stricter policies to safeguard personnel and to reduce the risk of transmission. Previous studies have shown a need for eye protection, protective clothing and the use of double-gloving during operative or interventional procedures. The risk of infection is much less with unbroken skin and conversely more likely when hollow needles are used. Arguments against the routine use of double-gloving include the loss of dexterity and the discomfort incurred, and the potential loss of dexterity that might theoretically result in more rather than fewer needle-stick injuries.", "A randomised trial was carried out to determine the rate of perforation to inner gloves when comparing latex with knitted gloves during hip and knee arthroplasty. Members of the surgical team were randomised to wear either two pairs of latex gloves (standard double gloving) or a knitted glove on top of a latex glove. In addition, participants completed a visual analogue assessment of their overall satisfaction with the gloves. A total of 406 inner gloves were tested for perforations over a four-month period: 23% of inner gloves were perforated when latex outer gloves were used and 6% of inner gloves were perforated when knitted outer gloves were used. In total, there were 64 perforations to the inner gloves; only one of these perforations was detected by the glove wearer. Wearing knitted outer gloves during hip and knee arthroplasty statistically significantly reduces the risk of perforation to inner latex gloves (p<0.0001)." ]

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[ "A prospective clinical trial comparing chemotherapy, radiotherapy and combined therapy in the treatment of early stage Hodgkin's disease with bulky disease.", "The management of stage I--II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience.", "Long term follow-up of combination chemotherapy-radiotherapy of stage III Hodgkin's disease: a Cancer and Acute Leukemia Group B study.", "Combined modality (ABVD plus radiotherapy) versus radiotherapy in the management of early stage (IIA) Hodgkin's disease with mediastinal involvement.", "[Combined radio- and chemotherapy of patients with stage I-II lymphogranulomatosis].", "Comparison of total nodal irradiation versus combined sequence of mantle irradiation with mechlorethamine, vincristine, procarbazine, and prednisone in clinical stages I and II Hodgkin's disease: experience of the European Organization for Research and Treatment of Cancer.", "[Radiotherapy in 50 cases of Hodgkin's disease in stages I and II. Report from the Lymphogranulomatosis Committee (LYGRA)].", "Current Stanford clinical trials for Hodgkin's disease.", "Chemotherapy and combined modality therapy for Hodgkin's disease: a progress report on Cancer and Leukemia Group B studies.", "Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group.", "Extended versus involved fields irradiation combined with MOPP chemotherapy in early clinical stages of Hodgkin's disease.", "Chemotherapy of Hodgkin's lymphoma with alternating cycles of COPP (cyclophosphamide, vincristin, procarbazine, prednisone) and ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Results of the HD1 and HD3 trials of the German Hodgkin Study Group.", "Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin's disease: eight-year update of an Italian prospective randomized study.", "A randomized study comparing chemotherapy alone with chemotherapy followed by radiotherapy in patients with pathologically staged IIIA Hodgkin's disease.", "A randomised study of adjuvant MVPP chemotherapy after mantle radiotherapy in pathologically staged IA-IIB Hodgkin's disease: 10-year follow-up.", "Radiotherapy versus radiotherapy plus chemotherapy in stages I and II Hodgkin's disease. A prospective, randomized study by the Danish National Hodgkin Study Group, LYGRA.", "Patients with stage III/IV Hodgkin's disease in partial remission after MOPP/ABV chemotherapy have excellent prognosis after additional involved-field radiotherapy: interim results from the ongoing EORTC-LCG and GPMC phase III trial. The EORTC Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie.", "Combined modality therapy of Hodgkin's disease: 10-year results of National Cancer Institute of Canada Clinical Trials Group multicenter clinical trial.", "Effect of ABVD chemotherapy with and without mantle or mediastinal irradiation on pulmonary function and symptoms in early-stage Hodgkin's disease." ]

[ "We performed a randomized clinical trial to assess the usefulness and toxicity of combined therapy compared with chemotherapy and radiotherapy in the treatment of early stage Hodgkin's disease with bulky disease as an adverse prognostic factor. Three-hundred and seven patients were enrolled into the study. They were randomized to receive either radiotherapy (extended field, generally mantle, 3500 cGy), or chemotherapy (adriamycin, bleomicin, vinblastine and dacarbazine: ABVD, 6 monthly) cycles or combined therapy (three cycles of ABVD, followed by irradiation therapy and three more cycles of chemotherapy). The median follow-up duration from start of treatment was 11.4 years. Complete response rates were similar in the three arms: 83% for radiotherapy (95% confidence interval [CI] 67-92%), 80% for chemotherapy (CI 69-88%) and 87% for combined therapy (CI 74-94%). However, disease-free survival and overall survival were better in the patients treated with combined therapy. At 12 years 76% (CI 51-93%) of the patients treated with combined therapy remained alive in the first complete remission compared with 42% (CI 26-61%) in patients treated with radiotherapy and 48% (CI 31-57%) in patients who had received chemotherapy alone (P < 0.01). Improvement in overall survival was also evident at 12 years: 88% (CI 59-93%) in those who had received combined therapy, compared with 53% (CI 36-67%) in the radiotherapy arm and 59% (CI 35-67%) in the chemotherapy group. Acute toxicity was more frequent in patients treated with combined therapy, but no death related treatment was observed in the three groups. Late toxicity was similar in the three treatment groups. Combined therapy with extended field radiotherapy and six cycles of chemotherapy is an effective treatment of patients with early stage bulky Hodgkin's disease compared with chemotherapy or radiotherapy alone.", "At Stanford University, between 1968 and 1978, 230 patients with pathologic stage I--II Hodgkin's disease were treated on prospective clinical trials with either irradiation alone or irradiation followed by 6 cycles of adjuvant combination chemotherapy. The actuarial survival at 10 yr was 84% for patients in either treatment group. Freedom from relapse at 10 yr was 77% among patients treated with irradiation alone and 84% after treatment with combined modality therapy [p(Gehan) = 0.09]. Freedom from second relapse at 10 yr was 89% and 94%, respectively [p(Gehan) = 0.56]. Several prognostic factors were evaluated in order to identify patients at high risk for relapse or with poor ultimate survival after initial treatment with irradiation alone. Systemic symptoms, histologic subtype, age, and limited extranodal involvement (E-lesions) did not affect the prognosis of patients and failed to identify patients whose survival could be improved by the routine use of combined modality therapy. Patients with large mediastinal masses (mediastinal mass ratio greater than or equal to 1/3) had a significantly poorer freedom from relapse when treated with irradiation alone than when treated initially with combined modality therapy [45% versus 81% at 10 yr, p(Gehan) = 0.03). The 10-yr survival of these patients, however, was not significantly different (84% versus 74%). The implications of these observations on the management of patient with early stage Hodgkin's disease are discussed.", "The Cancer and Acute Leukemia Group B studied the effect of combination chemotherapy-radiotherapy on Stage III Hodgkin's disease. Chemotherapy consisting of 4 weekly doses of vinblastine and one dose of mechlorethamine hydrochloride was followed by no therapy (CT), radiation to involved fields (CTIF) or total nodal radiation (CTTN). Two other treatment arms included total nodal radiation alone (TN) or total nodal radiation followed by chemotherapy (TNCT). Maximum follow-up is ten years. Complete remission percentages were 36 (8/22) for CT, 71 (17/24) for CTIF, 100 (21/21) for CTTN, 86 (19/22) for TNCT and 89 (16/18) for TN. Disease-free survival in patients receiving radiation +/- chemotherapy is 23% (19/73) at 5 years, but even after 9 years relapses were observed in two patients. Forty-one percent of all patients are alive and 32% have survived for five years. Ability to administer adequate therapy was the main determined for response duration and survival. Factors influencing the outcome of the disease include histology, age, splenectomy, initial white blood cell count and performance status, whereas symptomatology, initial absolute lymphocyte count and sex played no role on survival.", "The aim of this study was to establish whether combined modality treatment (ABVD plus radiotherapy) can reduce the risk of relapse in Hodgkin's disease patients with mediastinal involvement, as compared to radiotherapy alone. The results obtained suggest that one course of ABVD before irradiation can reduce the incidence of relapse. These findings, however, should be considered preliminary and need to be confirmed in larger studies.", "nan", "The H5 study of supradiaphragmatic Hodgkin's disease in clinical stages I-II consisted of two controlled trials adapted to patients considered to have either favorable or unfavorable characteristics, based on prognostic factors identified in two former studies by the European Organization for Research and Treatment of Cancer. Of 494 patients, 257 who were classified as having unfavorable prognosis qualified for the more intensive treatment and consequently were spared a staging laparotomy. They were randomized either to total nodal irradiation (TNI) (132 patients) or to treatment with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternated with mantle irradiation (MOPP X 3-mantle irradiation-MOPP X 3; 3M) (125 patients). In complete responders (96%), the 6-year relapse-free survival was 77% in the TNI arm and 91% in the 3M arm (P = .02). Relapses in the initially involved and irradiated mantle area were less frequent in patients started on MOPP. The 6-year actuarial total survival (TS) (TNI, 82%, and 3M, 89%; P = .05) appeared to favor the 3M arm, but this difference disappeared when patients dying from causes unrelated to cancer were excluded from analysis. In men less than or equal to 40 years old, there was no difference in relapse-free survival, freedom from disease progression, or TS between the groups receiving TNI and 3M. Thus, TNI is a short and appealing treatment, especially because it preserves fertility. The same observation was true in women less than or equal to 40 years old. In addition, even irradiation less than TNI, which is meant to spare the ovaries, provided a TS similar to that for 3M.", "nan", "nan", "Between 1974 and 1977, the Cancer and Leukemia Group B (CALGB) initiated four studies which address current major questions in the therapy for Hodgkin's disease. The efficacy of chemotherapy alone as compared with combined modality therapy in patients with poor-prognostic stages I and II is evaluated in CALGB 7751. Currently, both therapies produce very high complete remission rates in asymptomatic patients; the remission rate is better with combined modality therapy in symptomatic patients. Single and combined modality therapies are compared for stage III patients in CALGB 7451. Complete remission rates have been similar, but relapse-free survival is superior for patients treated with local nodal radiotherapy followed by chemotherapy (P = 0.04). In particular, stage IIIA patients with nodular sclerosis seem to benefit from the inclusion of radiotherapy in their initial treatment. In CALGB 7551, the efficacy of chemotherapy alone versus chemotherapy plus radiotherapy to areas of bulky disease is under study in patients with stages IIIB and IV. Currently, a relapse rate of less than 10% has been seen among sites irradiated, and survival is best for patients treated with radiotherapy bracketed by chemotherapy. Finally, the role of two alternating non-cross-resistant combination chemotherapy programs is being studied in CALGB 7552. Relapse-free and overall survival is better with the doxorubicin-containing regimen than with either the alternating or alternate chemotherapy program. At present, the median followup for each of these studies is less than 5 years. Further observation is required to answer the critical questions relating to prolonged disease-free survival and cure.", "To investigate whether radiotherapy can be reduced without loss of efficacy from extended field (EF) to involved field (IF) after four cycles of chemotherapy.\n Between 1993 and 1998, patients with newly diagnosed early-stage unfavorable HD were enrolled onto this multicenter study. Patients were randomly assigned to receive cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) + doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for two cycles followed by radiotherapy of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B).\n Of 1,204 patients randomly assigned to treatment, 1,064 patients were informative and eligible for the arm comparison (532 patients in arm A; 532 patients in arm B). The median observation time was 54 months. Five years after random assignment, the overall survival (OSran) for all eligible patients was 91% and freedom from treatment failure (FFTFran) was 83%. Survival rates at 5 years after start of radiotherapy revealed no differences for arms A and B, respectively, in terms of FFTF (85.8% and 84.2%) and OS at 5 years (90.8% and 92.4%). There also were no differences between arms A and B, respectively, in terms of complete remission (98.5% and 97.2%), progressive disease (0.8% and 1.9%), relapse (6.4% and 7.7%), death (8.1% and 6.4%), and secondary neoplasia (4.5% and 2.8%). In contrast, acute side effects including leukopenia, thrombocytopenia, nausea, gastrointestinal toxicity, and pharyngeal toxicity were more frequent in the EF arm.\n Radiotherapy volume size reduction from EF to IF after COPP + ABVD chemotherapy for two cycles produces similar results and less toxicity in patients with early-stage unfavorable HD.", "From 1976 to 1981, 335 patients with untreated Hodgkin's disease, clinical stages I, II, and IIIA, have been treated by MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy, three to six cycles according to the prognostic factors, combined with radiotherapy. Irradiation was always performed after the first three cycles of chemotherapy, and was randomized between extensive radiotherapy, ie, mantle and paraaortic areas for supradiaphragmatic presentations, and radiotherapy restricted to the involved areas. No significant difference was observed between the two randomized branches for the disease-free survival (86% after six years in the involved field branch v 90% in the extended field branch), and none for the overall survival. Most of the relapses occurred in nonirradiated areas in the first group, and in irradiated areas in the second. Relapses were especially frequent in the IIE stages with pulmonary extension; extranodal relapses occurred with osseous and cutaneous localizations. Two cases of secondary leukemia were observed after three- or six-cycle MOPP plus radiotherapy limited to the involved areas.", "Untreated patients with Hodgkin's lymphoma in stages I-IIIA with risk factors (large mediastinal mass, massive splenic involvement, extranodal disease) were entered into the HD1 protocol and received a combined chemo-radiotherapy [2 X (COPP + ABVD) + 40 Gy extended field irradiation (EF) vs 2 X (COPP + ABVD) + 20 Gy EF]. Patients in stages IIIB/IV (HD3 protocol) received induction chemotherapy [3 X (COPP + ABVD)] and were randomized into consolidation by radiotherapy [20 Gy involved field irradiation (IF)] vs chemotherapy [1 X (COPP + ABVD)]. Seventy-three of 89 evaluable patients (82%) treated according to the HD1 protocol achieved a complete remission. Freedom from progression and survival of patients in stages I-IIIA with risk factors treated according to HD1 were no worse than those of patients in stages I and II without risk factors who received only radiotherapy. Eighty-six of 137 patients (63%) treated according to the HD3 protocol achieved complete remission after induction chemotherapy with COPP + ABVD. This is significantly better than the 31% complete remission rate observed in a previous pilot study with COPP alone (P less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 X CEVD in case of persisting disseminated disease), a total of 76% complete remissions in stages IIIB/IVAB were achieved. A high erythrocyte sedimentation rate (greater than 80 mm h-1) was the most significant risk factor for achieving freedom from progression.", "To compare the effectiveness of chemotherapy (CHT) with extended-field radiotherapy (RT) in the treatment of early-stage Hodgkin's disease (ESHD), we report an 8-year updated analysis of a study in which treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) CHT was randomly compared with extended-field RT.\n From August 1979 to December 1982, 89 adult patients with pathologic stage I-IIA Hodgkin's disease (HD) were randomly allocated to receive either RT with mantle field followed by periaortic irradiation (n = 45) or six monthly courses of MOPP CHT (n = 44).\n All patients in the RT arm and 40 of 44 in the CHT arm achieved complete remission. Twelve relapses occurred in each group. Eight patients treated with MOPP and two of the RT arm died of HD. Three other patients of the CHT group died because of a second cancer. With a median follow-up greater than 8 years, the overall survival rate is significantly higher in the RT than in the CHT group (93% v 56%; P less than .001), whereas the rates of freedom from progression and relapse-free survival (RFS) were similar in the two groups (76% v 64% and 70% v 71%, respectively). Of the 12 patients relapsing after RT, 11 (92%) achieved a second CR, compared with only six of the 12 (50%) in the MOPP group. Analysis of the response rate to salvage treatments showed that the type of relapse in the MOPP group was a prognostic indicator for the achievement of a second CR, whereas in the RT group, a second CR was obtained regardless of the characteristics of the relapses. At 80 months, the probability of survival of relapsing patients calculated from time of relapse was 85% and 15% in the RT and CHT groups, respectively (P = .02).\n We conclude that RT alone is the treatment of choice for adult patients with ESHD with favorable prognostic factors.", "This paper reports the five-year follow-up (range, 1-8 years) of 56 patients with pathologic stage IIIA Hodgkin's disease randomized for chemotherapy alone or chemotherapy followed by radiotherapy to previous areas of disease (26 treated with mustine, vinblastine, procarbazine, and prednisolone [MVPP] alone, 30 with MVPP and radiotherapy). Of the 56 patients 53 (95%) achieved a complete remission with chemotherapy and of these only five (9%) have relapsed; three died of Hodgkin's disease. There was no improvement in relapse-free survival associated with the uses of radiotherapy following chemotherapy but in view of the small numbers of relapses and the excellent results following chemotherapy alone, a significant improvement could not be expected. The use of MVPP alone can be recommended as an alternative therapy for patients with stage IIIA Hodgkin's disease. This avoids both the physical and psychologic morbidity associated with the high relapse rate following extensive primary radiotherapy and the necessity of combined modality treatment for about half these patients. The question of whether radiotherapy should be given to areas of previous bulk following chemotherapy has not yet been answered in this trial which is continuing.", "One hundred fifteen untreated patients with supra-diaphragmatic, pathologically staged (PS) IA-IIB Hodgkin's disease (HD) were entered into a randomised study comparing treatment using mantle radiotherapy followed by adjuvant treatment with mustine, vinblastine, prednisolone, and procarbazine (MVPP) with mantle radiotherapy alone. Fifty-six patients were randomised to receive radiotherapy alone (RT) and 59 to radiotherapy followed by six cycles of adjuvant MVPP (RT + MVPP). One hundred fourteen patients achieved a complete remission (CR) with radiotherapy. One patient achieved a partial remission. The overall 10-year survival after correction for intercurrent death was 92% with no difference between the two treatment groups (90% for RT alone and 95% for RT + MVPP P = 0.66). There were 9 (8%) deaths from HD (5 patients had received RT alone), and 10 (9%) intercurrent deaths. Eight (7%) patients have developed a second malignancy, and two of them are alive. No patient has developed secondary acute myelogenous leukaemia. The 10-year relapse-free survival (RFS) was 79% overall, 67% in the RT group, and 91% in the RT + MVPP group (P = 0.0004). There were 25 relapses; 20 patients had received RT alone and 5 had received adjuvant MVPP. Of the relapsed patients, 13 (52%) have received successful salvage therapy and are in CR. In the RT alone group, 45 (80%) patients are alive in CR, 5 (9%) died of HD, and 6 (11%) died of intercurrent causes. In the adjuvant MVPP group, 51 (86%) are alive in CR, 4 (7%) died of HD, and 4 (7%) died of intercurrent causes.(ABSTRACT TRUNCATED AT 250 WORDS)", "In a multi-centre study in which data from all Danish Hodgkin patients have been registered since 1971, all patients in supradiaphragmatic stages I or II, as confirmed by staging laparotomy, were randomized to either radiotherapy (RT) to supra- and infradiaphragmatic lymph node regions (total nodal irradiation, TNI), or RT to a mantle field followed by 6 cycles of MOPP combination chemotherapy (RT+CT). Interim results up to July 1979, when 237 patients had entered the study, showed a treatment failure rate of 19/117 in the TNI group and 4/120 in the RT+CT group (P less than 0.05). 19 of the 23 relapsing patients were under the age of 40, and 14 in the TNI group and 3 in the RT+CT group belonged to stage II. 13 patients had nodular sclerosis, 9 had mixed cellularity and 1 had lymphocytic predominance histology. 12 of 19 relapsing patients in the TNI group had hilar or mediastinal involvement as against 51 of the 117 patients in the entire group. Most of the TNI failures could be retreated, and as yet there is no difference in the overall survival.", "Failure to reach complete remission (CR) with chemotherapy in advanced stages of Hodgkin's disease is considered a poor prognostic factor for progression-free and overall survival. The role of radiotherapy after chemotherapy-induced remission is controversial.\n In 1989, the EORTC/GPMC started a randomized phase III trial on involved-field RT (IF-RT) after MOPP/ABV hybrid-induced remission in patients with stage III/IV Hodgkin's disease. In this ongoing trial, patients in CR after chemotherapy are randomized between IF-RT and no further treatment. Patients in partial remission (PR) all receive IF-RT. Patients, age 15-70 years, with previously untreated stage III/IV Hodgkin's disease are eligible. The randomized treatment arms are still blinded. The interim analysis of May 1996 focuses on the outcome of patients in chemotherapy-induced PR.\n A total of 405 of 493 registered patients were evaluable for response to chemotherapy. Fifty-nine percent of patients attained a CR, 37% a PR, and only 4% failed to respond. The IF-RT was actually given to 90% of the PR patients. After a median follow-up of 43 months, the five year progression-free and overall survival for patients in PR was 75% and 87%, respectively.\n IF-RT after MOPP/ABV-induced partial remission in stage III/IV Hodgkin's disease produces excellent failure-free and overall survival. Early intensification of treatment of this group of patients is not indicated.", "The purpose of this study was to compare four methods of treatment for stage III-IV Hodgkin's disease. Between January 1972 and September 1976, 266 patients with stage IIIB, IVA, and IVB Hodgkin's disease from 21 cancer treatment centers across Canada were registered as eligible; 40 were found to be ineligible. Of the 226 remaining patients, only seven were followed for less than 10 years. All patients received three courses of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, which induced a complete response (CR) in 36%; an additional 42% obtained adequate disease control. Patients were randomly assigned to (1) treatment with radiation to the abdomen and mantle (group AX3, 62 patients) or (2) continue their treatment with an additional three courses of MOPP (group A, 105 patients). For the A group, a second randomization took place 3 months later (regardless of status at that time) to (1) no further treatment (AC6, 23 patients), (2) radiotherapy to the abdomen and mantle (AX6, 48 patients), or (3) maintenance chemotherapy at 3-month intervals for 1 year (AC10, 26 patients). The survival of AX3 patients was somewhat better than for the A group, but the difference was not significant (P = .0565). However, there was a significant interaction (P = .0029) between age and treatment, so that among patients less than 30 years of age, the survival of the A group was better, whereas for older patients, treatment with AX3 resulted in improved survival. Age itself remained a significant prognostic factor for survival after controlling for the amount of radiotherapy delivered to the abdomen and the dose intensity of vincristine for the first three courses of chemotherapy. The addition of radiation therapy to MOPP significantly reduced the frequency of nodal relapses. These results suggest that combined modality therapy may be beneficial for some patients with Hodgkin's disease and that age must be carefully considered in interpreting the results of clinical trials in Hodgkin's disease.", "To evaluate the effect of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy alone and of ABVD with mantle or mediastinal irradiation (RT) on the pulmonary function of patients with early-stage Hodgkin's disease.\n Between 1989 and 1993, 60 patients with clinical stage I to IIIA HD enrolled onto randomized trials at Memorial Sloan-Kettering Cancer Center (MSKCC) underwent prospective evaluation of pulmonary function. All patients received six cycles of ABVD, and 30 patients received mantle or mediastinal RT. Pulmonary function tests (PFTs) and symptom evaluation were conducted before, during, and after completion of chemotherapy and RT, and at various intervals thereafter. The median follow-up time was 30 months.\n During chemotherapy, symptoms of cough and dyspnea on exertion developed in 32 of 60 patients (53%) and declines in pulmonary function occurred in 22 of 60 patients (37%). Discontinuation of bleomycin was necessary in 14 of 60 patients (23%). Following chemotherapy, there was a significant decline in median forced vital capacity (FVC) and diffusing capacity of carbon monoxide (DLCO). In patients who received mantle or mediastinal RT, there was a further decline in FVC following radiation therapy. At the most recent follow-up evaluation, five of 29 patients (18%) who received ABVD alone and nine of 30 (30%) who received ABVD and RT reported persistent mild pulmonary symptoms (P = .36), which did not significantly affect normal daily activity.\n ABVD chemotherapy induced acute pulmonary toxicity that required bleomycin dose modification in a substantial number of patients. The addition of RT resulted in a further decrease in FVC; however, this did not significantly affect the functional status of patients." ]

[ "11886903", "1579034", "3334047" ]

[ "Closed reduction of colles fractures: comparison of manual manipulation and finger-trap traction: a prospective, randomized study.", "[Reposition of Colles' fracture--a new, more rapid, simpler and cheaper method].", "Reduction of Colles' fractures without anaesthesia using a new dynamic bone alignment system." ]

[ "An optimal outcome of closed treatment of a Colles fracture may depend on accurate reduction and adequate immobilization. It has been suggested that the use of finger-trap traction results in a better reduction and a lower rate of redisplacement than manual manipulation does, but to our knowledge these concepts have never been evaluated scientifically. We compared these two methods in a prospective, randomized controlled trial.\n Two hundred and twenty-three patients with 225 displaced Colles-type fractures were randomized to treatment with closed reduction with either finger-trap traction (112 patients) or manual manipulation (111 patients). The fractures were assessed radiographically by measurement of the radial angle, dorsal tilt, and radial shortening before reduction, immediately after reduction, and at one and five weeks after reduction.\n The groups were comparable with regard to age, sex, side of injury, fracture grade, and amount of displacement at presentation. No significant differences were found between the alignment of the fractures in the two treatment groups at any time. With dorsal tilt of <10 degrees and radial shortening of <5 mm considered acceptable, the two techniques both produced an 87% rate of satisfactory reductions. However, the percentages of fractures in an acceptable alignment were only 57% and 50% at one week after finger-trap traction and manual manipulation, respectively, and only 27% and 32% at five weeks. The failure rates did not differ significantly between the two groups.\n The two methods of fracture reduction did not differ with regard to the eventual position of the fracture or the rate of failure. Although closed reduction was successful for the majority of fractures, most redisplaced substantially during the period of cast immobilization.", "nan", "Two techniques for reduction of Colles' fractures were compared in a prospective, randomized study. With use of a newly designed dynamic bone alignment device, reduction manoeuvres were performed on 62 patients with Colles' fractures (group A) without any form of anaesthesia. In a control group of 54 patients (group B) Colles' fractures were reduced manually in the traditional way using local infiltration anaesthesia. In each group the pain experienced by the patients was recorded. Severe pain during the reduction was reported by 8 per cent of the patients in group A and by 35 per cent of those in group B. No complications occurred during or after dynamic reduction without anaesthesia. This method of treatment seems to be a very gentle one for the patients, with the advantage of causing less pain than treatment under local anaesthesia." ]

[ "22000905", "18486508", "11937721", "18849052", "18245406", "7593655", "17429911", "9659093", "18840204" ]

[ "A double-blind randomised controlled trial of 25% oral glucose for pain relief in 2-month old infants undergoing immunisation.", "Stress at three-month immunization: parents' and infants' salivary cortisol response in relation to the use of pacifier and oral glucose.", "Intra-oral administration of sweet-tasting substances and infants' crying response to immunization: a randomized, placebo-controlled trial.", "Interventions to reduce pain during vaccination in infancy.", "Analgesic properties of oral sucrose during routine immunizations at 2 and 4 months of age.", "\"Sucrose analgesia\" and diphtheria-tetanus-pertussis immunizations at 2 and 4 months.", "Oral glucose as an analgesic to reduce infant distress following immunization at the age of 3, 5 and 12 months.", "Randomised controlled trial of sucrose by mouth for the relief of infant crying after immunisation.", "Sucrose decreases infant biobehavioral pain response to immunizations: a randomized controlled trial." ]

[ "Infant immunisation is the most commonly performed health procedure in developed countries. Associated pain may be harmful because we do not know what painful experiences the infant has already had and whether it might contribute to a cumulative pain experience. Healthy infants undergo immunisation with minimal pain relief. However, immunisation pain can be managed using oral sweet solutions.\n To determine the effectiveness of 25% oral glucose solution in reducing immunisation pain in 2-month old infants. TRIAL DESIGN AND METHODS: A double-blind, randomised controlled trial conducted in Jordan. A total of 120 healthy full-term infants who met the eligibility criteria and were attending immunisation clinics for routine 2-month immunisation were randomised to receive either 2 mL of 25% oral glucose solution immediately prior to their immunisation or 2 mL of oral sterile water. Researchers, nurses and parents were blind to the solution. Primary outcome was behavioural pain measured using the Modified Behavioural Pain Scale (MBPS). Secondary outcomes were crying time and duration of full-lung cry. Crying was registered from onset of the immunisation injection and for up to 120 s after completion of the injection procedure.\n Infants in the intervention group experienced statistically and clinically significant reduction in behavioural pain responses (p<0.001), and spent less time crying up to 2 min after the procedure (mean difference 38 vs. 77.9s).\n A 2 mL oral dose of 25% glucose given immediately before an immunisation procedure reduces pain in 2-month old infants.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "The aims of the present study were to investigate (1) whether the salivary cortisol response could be dampened during a routine three-month immunization if the infant received sweet-tasting solution in combination with a pacifier and (2) stress experienced by parents during immunization of the infant. Ninety-eight infants were included into one of four intervention groups: 'glucose and pacifier', 'water and pacifier', 'glucose', or 'water'. Saliva was collected before and 30 min after the immunization. Infants' crying-time and parents' self-reported stress (VAS) were measured before and after immunization. Infants in the 'pacifier and glucose' group had a significantly smaller change in salivary cortisol than infants in the other groups (F(3,72)=3.1, p<0.05). In the 'glucose and pacifier' group the median salivary cortisol levels decreased 33% after the immunization. In the 'water and pacifier', 'glucose', and 'water' group median cortisol increased with 50%, 42%, and 8%, respectively. No significant differences in crying-time were observed between the intervention groups. If the infant cried before the immunization, the crying-time during the immunization was longer (p<0.01) and cortisol increased more (p<0.05). Median cortisol levels for parents decreased after the immunization (p<0.01). Median VAS increased 50% (p<0.0001) after immunization. First time parents rated higher stress on VAS before immunization (p<0.01). Parents' change in cortisol and VAS were significantly related to infants' crying time. In conclusion, the combination of oral glucose and pacifier dampen infants' salivary cortisol in response to the three-month immunization.", "The analgesic effects of four solutions administered intra-orally (25 and 50% sucrose solutions, hydrogenated glucose, and a sterile water placebo) were tested in groups of babies receiving routine DTP (diphtheria, tetanus, and pertussis) and HIB (Haemophilus influenzae type B) injections at the first, second, or third immunization. The duration of the baby's cry during 3 min following DTP and HIB injections was measured as main outcome. For all three immunization groups, the babies receiving the placebo generally spent most time crying. For both the DTP and HIB injections, the difference between 50% sucrose and placebo was most evident in the group receiving the 3rd immunization. Intra-oral administration of the 50% sucrose solution, compared to placebo, appeared to reduce the cry response to painful experiences in babies beyond the neonatal period.\n Copyright 2002 S. Karger AG, Basel", "To investigate interventions that affect pain reduction during vaccination in infants and children attending a well-child unit.\n A consecutive sample of 243 children between age 0 and 48 months receiving their routine vaccinations was randomly assigned to 1 of the study groups. A total of 158 infants under age 6 months were randomly assigned to breast-feeding or no breast-feeding during immunization, and 85 children age 6 to 48 months were randomly assigned to receive 12% sucrose solution, lidocaine-prilocaine cream, or no intervention. All children were evaluated for crying time and pain score by a pediatrician using the Neonatal Infant Pain Scale (NIPS) for those under age 12 months and the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) for those over age 12 months.\n Breast-feeding in infants under age 6 months and use of sucrose or lidocaine-prilocaine in children age 6 to 48 months significantly reduced crying time and pain scores compared with controls. No difference in outcome was seen between the sucrose and lidocaine-prilocaine treatment groups.\n Here we expand on previous findings by demonstrating that breast-feeding may have an analgesic effect up to age 6 months and that in older children, both sucrose and lidocaine-prilocaine reduce vaccination pain.", "The purpose of this work was to evaluate the analgesic properties of oral sucrose during routine immunizations in infants at 2 and 4 months of age.\n A prospective, randomized, placebo-controlled clinical trial was conducted at a pediatric ambulatory care clinic. One-hundred healthy term infants scheduled to receive routine immunizations were recruited, randomly stratified into 2- or 4-month study groups, and further randomly assigned to receive 24% oral sucrose and pacifier or the sterile water control solution. The study preparations were administered 2 minutes before the combined diphtheria-tetanus-acellular pertussis, inactivated polio vaccine, and hepatitis B vaccine. Haemophilus influenzae type b vaccine was administered 3 minutes after the combined injection, followed by the pneumococcal conjugate vaccine, 2 minutes after the H. influenzae type b injection. The University of Wisconsin Children's Hospital Pain Scale measured serial acute pain responses for the treatment and control groups at baseline and 2, 5, 7, and 9 minutes after solution administration. Repeated-measures analysis of variance examined between-group differences and within-subject variability of treatment effect on overall pain scores.\n Two- and 4-month-old infants receiving oral sucrose (n = 38) displayed reductions in pain scores 2 minutes after solution administration compared with 2- and 4-month-old infants in the placebo group (n = 45). Between-group comparisons for the oral sucrose and placebo groups showed lower pain responses at 5, 7, and 9 minutes after solution administration. The oral sucrose and placebo groups demonstrated their highest mean pain score at 7 minutes, with a mean pain score of 3.8 and 4.8, respectively. At 9 minutes, the placebo group had a mean pain score of 2.91 whereas the mean pain score for the oral sucrose group returned to near baseline, reflecting a 78.5% difference in mean pain score (oral sucrose - placebo) relative to the placebo mean.\n Oral sucrose is an effective, easy-to-administer, short-acting analgesic for use during routine immunizations.", "In human newborns, small amounts of sucrose reduce crying with procedural pain by about 50%. To determine whether \"sucrose analgesia\" could be extended to painful procedures beyond the newborn period, 57 infants were randomly assigned to receive three 250-microliters doses of 50% sucrose solution (g/100 mL) or water before their diphtheria-tetanus-pertussis immunizations at 2 and 4 months of age. Crying during and after injection was measured separately to determine whether sucrose modified crying during the noxious stimulus, recovery from the stimulus, or both. Sucrose was effective in reducing crying only from 83 to 69%, and the reduction was limited to the postinjection period. We conclude that, although sucrose continues to have some effect beyond the newborn period, the effect is limited to recovery from the noxious stimulus, is clinically modest, and is probably smaller than in the newborn period.", "To evaluate oral glucose as an analgesic to reduce infant distress after immunization during the first year of life and to investigate if these effects change during this period.\n A prospective controlled trial of the effectiveness of glucose on crying response to immunizations at 3, 5 and 12 months of age. A total of 110 infants were randomized to receive 2 mL of 30% glucose or water. The same solution was given at 3, 5 and 12 months. Crying was registered from onset of the injection up to 120 seconds. Infanrix Polio Hib was administered intra-muscular in the thigh. Observation nurse and parents were blind to the nature of the solution.\n Administration of glucose reduced the mean crying time by 22% at 3 months, 62% at 5 months and 52% at 12 months. The difference was significant at 5 and at 12 months. In the water group, there was a significant correlation between the children who cried at 3 months and who subsequently cried at 5 and 12 months. No correlations were found in the glucose group.\n Sweet solution can be used as a simple and safe method to reduce the distress following immunization in infants up to 12 months.", "To evaluate the effect of sucrose solution given by mouth on infant crying times and measures of distress in the immunisation clinic.\n Randomised, double blind, placebo controlled trial of sucrose solution 75% wt/vol v sterile water as a control.\n The immunisation clinic of the Women's and Children's Hospital, Adelaide.\n A total of 107 healthy infants attending for 2, 4, or 6 month immunisations with polio by mouth (Sabin), intramuscular diphtheria, tetanus, and pertussis (DTP), and intramuscular Haemophilus influenzae type b were randomised to receive 2 ml 75% sucrose solution or sterile water by mouth before the two injections.\n The duration of infant crying was recorded during and immediately after two intramuscular immunisations and infant distress was assessed by a visual analogue scale (Oucher scores) independently by a nurse and a parent.\n The administration of 2 ml 75% sucrose solution by mouth reduced the infant crying time and Oucher distress scores after immunisation with DTP/H influenzae type b.\n Infant immunisation by intramuscular injection is a distressing procedure for infants and parents. Sucrose solution at a high concentration reduces infant distress and is safe and clinically useful in this setting.", "To evaluate the effectiveness and age-related changes in analgesia of oral sucrose as a preprocedural intervention during routine immunizations in infants at 2 and 4 months of age.\n A double-blind, randomized, placebo-controlled clinical trial of 40 healthy term infants scheduled to receive routine immunizations from a pediatric ambulatory care clinic during May 2005 to July 2005.\n Infants received 24% oral sucrose solution or the control solution of sterile water 2 minutes before routine immunizations at both their 2- and 4-month, well-child visits. The University of Wisconsin Children's Hospital pain scale was used to measure serial acute behavioral pain responses at baseline, 2, and 5 minutes after administration of the solution. Repeated measures ANOVA was used to examine between-group differences and within-subject variability of the effects of treatment on overall behavioral pain scores.\n Infants receiving oral sucrose (n=20) showed a significant reduction in behavioral pain response 5 minutes after administration compared to those in the placebo group (n=20). At 2 minutes following solution administration, both sucrose and sterile water showed the highest mean pain score (4.54 and 4.39 respectively) indicating a severe amount of pain. At 5 minutes, the sucrose group returned to near normal at 0.27 while the placebo group remained at 3.02 indicating a percentage difference in mean pain scores relative to sterile water pain scores of 90.9. No statistically significant age-related change in behavioral pain response was noted between 2- and 4-month-old infants at 2 minutes and 5 minutes following treatment administration.\n Sucrose is an effective preprocedural intervention for decreasing behavioral pain response in infants after immunizations.\n Efforts to decrease the pain associated with immunizations can promote parental adherence to recommended immunizations schedules, prevent a resurgence of vaccine-preventable diseases and mitigate adverse neurologic outcomes in infants." ]

[ "15583955" ]

[ "Neuroprotective treatment with cerebrolysin in patients with acute stroke: a randomised controlled trial." ]

[ "Cerebrolysin is a compound with neurotrophic and neuroprotective activity. It is produced by enzymatic breakdown of purified brain proteins and consists of low molecular weight peptides and amino acids. Cellular and animal models of cerebral ischaemia have shown that it is a potent neuroprotective agent. We explored the safety and preliminary outcome of Cerebrolysin treatment in patients with acute stroke.\n Randomised, placebo-controlled, parallel group trial. Patients with acute stroke were randomised within 24 h of stroke onset to IV therapy with placebo or Cerebrolysin 50 mL/day for 21 days. Both groups received concomitant treatment with ASA 250 mg/day PO and pentoxifylline 300 mg/day IV. Clinical examinations were performed on days 1, 3, 7, 21 and 90 post baseline. Outcome measures were the Canadian Neurological Scale, the Barthel Index, the Clinical Global Impressions, the Mini-Mental State Examination, and the Syndrome Short Test. Treatment emergent adverse events, lab tests, and vital signs were recorded to assess the safety of Cerebrolysin.\n 146 patients were enrolled in two groups: 78 Cerebrolysin and 68 placebo. At baseline, no significant group differences were observed. Patients in the Cerebrolysin group had no significant improvement in the CNS score, the Barthel Index and the Clinical Global Impressions when compared to the placebo group. A significant improvement of cognitive function of the patients on Cerebrolysin was observed in the Syndrome Short Test when compared to the placebo group. Cerebrolysin was well tolerated and safe. Adverse events occurred with a similar frequency in both groups.\n The results demonstrate that neurotrophic treatment with Cerebrolysin is safe and well tolerated by patients with acute stroke. The findings, despite the small sample size, also indicate a potential treatment effect of Cerebrolysin in acute stroke. Larger studies, however, are needed to confirm and extend these findings." ]

[ "9565715" ]

[ "Fluoxetine in depressed patients on dialysis." ]

[ "To test the safety and efficacy of fluoxetine in patients with renal failure on dialysis.\n Fourteen patients with major depression and end stage renal disease on hemodialysis were randomized into two groups for an eight-week study. Subjects as well as investigators were blinded as to which subject received fluoxetine and which placebo. Patients were carefully monitored concerning adverse events, serum fluoxetine and norfluoxetine levels, and psychological measurements of degree of depression.\n No patients discontinued treatment because of adverse events, all of which were minor. All psychological tests showed improvement in depression at the four-week and eight-weeks point, although statistical significance could only be demonstrated at the fourth week of this study. All patients in the active group had serum plasma concentrations of fluoxetine and norfluoxetine less than 250 ng/ml at eight weeks, similar to levels in patients with normal renal function in a previous open label study.\n This study confirms the relative safety of fluoxetine in depressed patients in renal failure on hemodialysis. It also suggests that fluoxetine may be efficacious in depressed patients on dialysis." ]

[ "17219106" ]

[ "Full macular translocation versus photodynamic therapy with verteporfin in the treatment of neovascular age-related macular degeneration: 1-year results of a prospective, controlled, randomised pilot trial (FMT-PDT)." ]

[ "The purpose of this study was to compare full macular translocation (FMT) with photodynamic therapy (PDT) in the treatment of neovascular age-related macular degeneration (AMD).\n In a prospective, randomised, non-masked, mono-center, pilot-trial, 50 eyes of 50 patients were assigned to either FMT or PDT. Baseline and control examinations in 3-monthly intervals over a 12-month period included standardized protocol refraction, visual acuity testing and fluorescein angiography. Primary outcome measurements were made to establish the change in distant visual acuity from the baseline to the 12-month examination. The statistical analyses were carried out on the intent-to-treat principle.\n The improvement of one or more ETDRS lines was 56% (14/25) of the eyes in the FMT and 16% (4/25) of the eyes in the PDT arm (P = 0.007). Twenty eyes (80%) in the FMT and 16 eyes (64%) in the PDT group had less than three ETDRS lines of vision loss (P = 0.35). Retinal detachment (six eyes) and diplopia (five patients) were recorded in the FMT group. None of the eyes treated in the FMT group had phtysis.\n This pilot study showed that no statistically significant difference existed between the FMT and PDT in terms of the vision loss of less than three ETDRS lines in eyes with neovascular AMD. The chance of vision improvement was significantly higher for the patients in the FMT group. However, in the era of promising therapy with anti-vascular endothelial growth factor for neovascular AMD, FMT should not be offered as a standard primary procedure for neovascular AMD." ]

[ "10711472", "2237768", "12001325", "7827744" ]

[ "Intermittent pump versus compression bandages in the treatment of venous leg ulcers.", "Sequential gradient pneumatic compression enhances venous ulcer healing: a randomized trial.", "Intermittent pneumatic compression as an adjuvant therapy in venous ulcer disease.", "Intermittent pneumatic compression improves venous ulcer healing." ]

[ "The purpose of the present paper was to compare healing rate and leg swelling with an intermittent compression pump versus compression bandages in the treatment of venous leg ulcers, and to also compare patient compliance and satisfaction with the two techniques.\n A randomized cross-over study of patients attending an outpatient wound clinic (n = 16) was undertaken. A regular monthly follow-up with measurement of ulcer size and leg volume was carried out, as well as completion of a questionnaire.\n Assessment was possible in 11 of the 16 patients. There was no significant difference between treatment types with regards to ulcer healing rates or control of leg oedema. The survey revealed that patients found the pump easier and more comfortable to use, with a trend towards increased compliance.\n Although the present study was too small for generalizable conclusions, compression pumps and bandages are comparable in efficacy for the healing of venous leg ulcers. The compression pump is reported as being easier and more comfortable to use than bandages.", "The treatment of venous ulcers has remained largely unchanged for centuries. The application of properly applied graduated compression bandages, the use of graduated compression stockings, and surgery have been shown to achieve healing. However, some ulcers persist despite appropriate management. A randomized study was undertaken to compare two regimens of treatment for such patients. Both regimens included ulcer debridement, cleaning, nonadherent dressing, and graduated compression stockings. In one regimen, sequential gradient intermittent pneumatic compression was applied for 4 hours each day. Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group. The median rate of ulcer healing in the control group was 2.1% area per week compared to 19.8% area per week in the intermittent pneumatic compression group. The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers.", "Despite improvements in healing rates venous ulcer disease still carries significant morbidity and cost. Any therapy that further improves healing rates is worthy of consideration. The recognised effects of intermittent pneumatic compression (IPC) on both arterial and venous circulation suggest that its use may confer significant benefits to venous ulcer healing. This study investigates the potential additive effects of adjuvant IPC on the healing and subsequent prevention of venous ulcers. Some improvement in the rate of healing in venous ulcers is noted. These findings are set against a background of very high healing rates in both treatment and control groups. No benefit is seen to accrue if IPC is used as an adjuvant therapy to help prevent recurrence of ulcers although the study period is very short.", "The effects of intermittent pneumatic compression on the healing rates of ulcers in patients with chronic venous insufficiency were examined in a prospective, controlled study of 22 patients. Patients were randomly assigned to the experimental or the control group. Both groups received local wound care followed by application of an Unna boot. In addition, subjects in the experimental group received intermittent pneumatic compression (IPC) twice weekly for one hour each session. Healing rates were reported in square centimeters per day. Data analysis revealed a mean healing rate of 0.08 cm2 per day for control subjects and 0.15 cm2 per day for experimental subjects. Statistical analysis, demonstrated the healing rates of the two groups to be statistically different. The results appear to indicate that intermittent pneumatic compression is beneficial in the management of venous insufficiency ulcers." ]

[ "9710387", "2003660", "12923753", "15086180", "3670868", "14726734", "8165081", "12725195", "12719743", "11252881", "3635599", "18493472", "14651700", "10353504", "1735869", "11472279", "10531890", "10460529", "10460982", "9592448", "11302355", "1762973", "12648193", "10076111", "1857652", "12886915", "9879163", "14742400", "2406782", "10553182", "14529684", "2643088", "12836149", "11953285", "10742370", "8826769", "12597931", "11353359", "9542366", "2704576", "11756911", "7879724", "7862546", "11310081", "3058899" ]

[ "The sedative and analgesic sparing effect of music.", "A randomized, controlled trial of the use of music during laceration repair.", "The effect of two nursing interventions on the postoperative outcomes of gynecologic laparoscopic patients.", "Reduction in salivary cortisol level by music therapy during colonoscopic examination.", "Management of injection pain in children.", "Burn pain and anxiety: the use of music relaxation during rehabilitation.", "Age-related response to lidocaine-prilocaine (EMLA) emulsion and effect of music distraction on the pain of intravenous cannulation.", "Effects of patient-controlled music therapy during coronary angiography on procedural pain and anxiety distress syndrome.", "Music versus distraction for procedural pain and anxiety in patients with cancer.", "The effects of music on cardiac patients on bed rest.", "The effect of music as a conditioning aid in prepared childbirth education.", "Stress reduction through listening to Indian classical music during gastroscopy.", "Effect of music on chronic osteoarthritis pain in older people.", "Relief of postoperative pain with jaw relaxation, music and their combination.", "Effect of music therapy in the postanesthesia care unit: a nursing intervention.", "Improved recovery after music and therapeutic suggestions during general anaesthesia: a double-blind randomised controlled trial.", "Children's responses to immunizations: lullabies as a distraction.", "Hemispheric-synchronisation during anaesthesia: a double-blind randomised trial using audiotapes for intra-operative nociception control.", "[Investigations into synchronisation of heart rate and musical rhythm in a relaxation therapy in patients with cancer pain].", "The effect of music in the postanesthesia care unit on pain levels in women who have had abdominal hysterectomies.", "Brief cognitive interventions for burn pain.", "The therapeutic use of music for cancer-related pain.", "Analgesia following music and therapeutic suggestions in the PACU in ambulatory surgery; a randomized controlled trial.", "Intradermal normal saline solution, self-selected music, and insertion difficulty effects on intravenous insertion pain.", "Pain reduction interventions during neonatal circumcision.", "A comparison of intra-operative or postoperative exposure to music--a controlled trial of the effects on postoperative pain.", "Music does not reduce alfentanil requirement during patient-controlled analgesia (PCA) use in extracorporeal shock wave lithotripsy for renal stones.", "The effect of music on the neurohormonal stress response to surgery under general anesthesia.", "Relaxation response in femoral angiography.", "Music: an intervention for pain during chest tube removal after open heart surgery.", "The use of music to reduce anxiety for patients undergoing colposcopy: a randomized trial.", "Effects of music and imagery on physiologic and self-report of analogued labor pain.", "Music reduces sensation and distress of labor pain.", "Improved procedure of colonoscopy under accompanying music therapy.", "Soothing pain-elicited distress in Chinese neonates.", "The effects of music interventions on postoperative pain and sleep in coronary artery bypass graft (CABG) patients.", "Music decreases anxiety and provides sedation in extracorporeal shock wave lithotripsy.", "Evaluation of pain management interventions for neonatal circumcision pain.", "The effects of Western music on postoperative pain in Taiwan.", "Pain reduction during neonatal circumcision.", "Relaxation music decreases the dose of patient-controlled sedation during colonoscopy: a prospective randomized controlled trial.", "Taped therapeutic suggestions and taped music as adjuncts in the care of coronary-artery-bypass patients.", "A comparison of the effects of jaw relaxation and music on postoperative pain.", "Effects of a single music therapy intervention on anxiety, discomfort, satisfaction, and compliance with screening guidelines in outpatients undergoing flexible sigmoidoscopy.", "Music for postoperative pain and anxiety." ]

[ "To determine whether music influences intraoperative sedative and analgesic requirements, two randomized controlled trials were performed.\n In phase 1, 35 adults undergoing urologic procedures with spinal anesthesia and patient-controlled intravenous propofol sedation were randomly assigned to hear favorable intraoperative music via headset or to have no music. In phase 2, 43 adults undergoing lithotripsy treatment of renal or ureteral calculi and receiving patient-controlled intravenous opioid analgesia were randomly assigned to either a music or no-music group. The effect of music on sedatives and analgesics requirements, recovery room duration, and adverse outcomes was assessed.\n In phase 1, patients in the music group required significantly less propofol for sedation than patients in the control group (0 [0-150] mg vs. 90 [0-240] mg, median[range]; P < 0.001). These findings persisted after adjusting for duration of surgery (0.3+/-0.1 mg/min vs. 1.6+/-0.4 mg/min; P < 0.001). Similarly, in phase 2, patients who listened to music had a significant reduction in alfentanil requirements (1,600 [0-4,250] microg vs. 3,900 [0-7,200] microg; P = 0.005). This persisted after adjusting for duration of surgery (52+/-9 microg/min vs. 119 +/-16 microg/min, mean +/- SD, P < 0.001). Duration of stay in the postanesthesia care unit and the rate of adverse events was similar in both groups (P = NS).\n Use of intraoperative music in awake patients decreases patient-controlled sedative and analgesic requirements. It should be noted, however, that patients in the no-music group did not use a headset during operation. Thus, the decrease in sedative and analgesic requirements could be caused by elimination of ambient operating room noise and not by the effects of music.", "To determine whether music significantly reduces the pain and anxiety associated with laceration repair in the emergency department.\n Adult patients presenting to the ED at an urban teaching hospital for laceration repair. Exclusion criteria included patients less than 18 years old, having received analgesics, with suspected alcohol or substance intoxication, and in whom laceration repair was complicated by treatment of a more serious medical condition.\n This was a randomized, controlled trial. After giving informed consent, patients were randomly assigned to receive standard laceration repair without music (control) or standard laceration repair with music. Patients assigned to the music group chose an audio tape from 50 available styles and artists. Patients received the music through a headset, and they controlled the volume. Intradermal lidocaine was used in all patients. Data were collected on heart rate, blood pressure, and respirations just before and immediately after wound repair. Psychological variables included the state subscale of the Spielberger State Trait Anxiety Inventory (STAI), a visual analog pain scale rating, and a brief questionnaire. STAI and pain scale ratings were analyzed with Wilcoxon's rank-sum test with an alpha error of .05.\n Thirty-eight patients (19 per group) completed the protocol. Pain scores were significantly (P less than .05) lower in the music group (mean, 2.09) than in controls (mean, 3.31). Anxiety after the procedure was reduced in both groups, but STAI reduction scores were not significantly different between groups (music, 17.7; control, 18.5). Seventeen of 19 patients (89%) rated music \"very beneficial,\" and 100% said they would use music again.\n Music provides a safe, inexpensive, and effective adjunct for the management of pain in the ED but does not significantly affect anxiety.", "Anecdotal reports support research findings in documenting the high incidence of negative postoperative outcomes after gynecologic (GYN) laparoscopic surgery. Three outcome measures, postoperative pain, postoperative nausea and vomiting (PONV), and length of stay, have received considerable attention. Two nursing interventions frequently suggested for their positive effects are guided imagery and music therapy. An experimental pilot study was conducted to determine the effects of these nursing inventions on postoperative pain, PONV, and length of stay for GYN laparoscopic patients (n = 84). During the perioperative period, patients were randomly assigned to one of 3 interventions: guided imagery audiotapes (GI), music audiotapes (MU), or standard care (C), and outcome measures were evaluated. Results indicated that patients in both the guided imagery and music groups had significantly less pain on PACU discharge to home than the patients in the control group. These findings suggest that both guided imagery and music are effective strategies in improving pain, a difference that becomes apparent when the patient is ready to be discharged. It is possible that these interventions act as distractions in reducing the report of negative postoperative outcomes.", "Premedication for endoscopy promotes patient cooperation and makes subsequent examinations more acceptable. Music therapy is widely used in the treatment of acute and chronic pain. Therefore, we investigated the effects of music therapy on pain and on salivary cortisol levels in patients undergoing screening colonoscopy.\n The subjects were 29 consecutive patients undergoing colonoscopy for various reasons. Patients were randomly assigned to undergo colonoscopy while listening to music (n=15) or while not listening to music (n=14). Cortisol levels were measured in samples of saliva obtained before and after colonoscopy. After colonoscopy, patients were asked to rate their maximum pain during colonoscopy.\n Patients who listened to music during colonoscopy tended to have lower pain scores. Salivary cortisol levels increased significantly less in the group receiving music.\n Music therapy during colonoscopy markedly reduces fear-related stress, as indicated by changes in salivary cortisol levels.", "Researchers have come to understand a great deal about pain mechanisms, especially in the past 30 years. This understanding has spawned the development of a number of psychological pain control strategies which have been extensively assessed for use with adults. Less is known about pain control strategies in children. The purpose of this study was to assess the value of 2 cognitive strategies (suggestion and music distraction) in reducing pain in children. Two hundred children, aged 4.5-6.5 years, receiving routine immunization injections were randomly assigned to one of the intervention groups in this factorial study. The groups were designated as: distraction, distraction with suggestion, suggestion and control. Subjects reported their pain using a 4-point pain scale. Distraction was found to significantly decrease pain whereas suggestion did not. Combining suggestion and distraction did not further enhance pain relief compared to use of distraction alone. Age was found to be an important determinant of the success of distraction. Furthermore, age was found to be related to amount of pain reported by children regardless of type of treatment. The results of this study support the use of music distraction in the reduction of injection pain in children.", "Pain and anxiety are well-documented problems during the rehabilitation of patients with burns. This study examined the effect of music on anxiety and pain during range of motion. Eleven subjects with partial-thickness or deeper burns were randomly assigned to a control group (without music intervention) or experimental group (with music intervention). Vital signs, pain, and anxiety were recorded before and after treatments. There was no difference in pretest and posttest anxiety across the groups; however, there was a difference in anxiety between the groups. Conversely, there was a difference in pretest and posttest pain across the groups but no difference in pain between the groups. Results showed no significant reduction in anxiety and pain during therapy with music relaxation. Limitations included nonhomogenous groups, small sample size, potentially unrepresentative sample, variation in exercise protocol, and small musical selection. Further research is recommended.", "To compare the efficacy of a local anesthetic cream and music distraction in reducing or preventing pain from needle puncture (intravenous cannulation) in children. A secondary aim was to examine the influence of age on the pain report and behavior and on the therapeutic outcome.\n Children aged 4 to 16 years (N = 180) who were to undergo surgery under general anesthesia via intravenous cannulation were randomly allocated to one of three interventions. The comparison of lidocaine-prilocaine emulsion (EMLA, Astra) and a placebo emulsion was double-blind. Stratification by age group (4 to 6, 7 to 11, 12 to 16) ensured an equal number of children (20) in each intervention/age group category. A global assessment of the behavioral reaction to the procedure was made by the principal investigator, taking into account vocal, verbal, facial, and motor responses. The child was asked to assess pain severity on the Faces Pain Scale (FPS) and a visual analogue toy (VAT). The scales were applied conservatively as ordinal scales: FPS 0 to 6; VAT 0 to 10.\n Children who received lidocaine-prilocaine emulsion reported less pain (mean FPS score = 1.42) compared with placebo emulsion (mean FPS score = 2.58) and with music distraction (mean FPS = 2.62). There was a highly significant therapeutic effect (P < .001) on the self-report and behavioral scores. Younger children, regardless of intervention, reported significantly more pain than the older children (mean FPS scores: 2.85, 2.33, 1.43 for age groups 4 to 6, 7 to 11, and 12 to 16 respectively; P < .001). The superiority of the local anesthetic emulsion was maximal in the youngest age group (4 to 6) almost eliminating pain-related behavior, and multiple regression analysis confirmed significant age and treatment effects and revealed interaction between therapeutic effect and age. Although a trend favoring the active emulsion was evident in the older children (7 to 11, 12 to 16) the differences were not significant. The pain scores were influenced by the type (gauge) of cannula, but this did not affect the conclusion regarding therapeutic and age effects. There was no influence of sex, experience with venipuncture, or whether the child was anxious on arrival in the operating room.\n The results show that lidocaine-prilocaine emulsion is highly effective in preventing pain from venipunctures in young children, the group in most need of prevention.", "nan", "To test the hypotheses that the effects of a music intervention are greater than those of simple distraction and that either intervention is better at controlling procedural pain and anxiety than treatment as usual.\n Randomized, controlled experiment.\n A midwestern comprehensive cancer center.\n 60 people with cancer having noxious medical procedures such as tissue biopsy or port placement or removal; 58 provided usable data.\n Participants completed measures of pain and anxiety before and after their medical procedures and provided a rating of perceived control over pain and anxiety after the procedure.\n Procedural pain, state anxiety, and perceived control over pain and anxiety.\n Contrary to hypotheses, outcomes achieved with music did not differ from those achieved with simple distraction. Moreover, outcomes achieved under treatment as usual were not significantly different from those obtained with music or distraction interventions. Some patients found that the interventions were bothersome and reported that they wanted to attend to the activities of the surgeon and the medical procedure itself.\n The effects of music, distraction, and treatment as usual are equivocal. In addition, patients have individual preferences for use of distraction during painful or anxiety-provoking procedures.\n Patients having noxious medical procedures should be asked about their desire to be distracted before and during the procedure and offered a strategy that is consistent with their preferences.", "Hospitalizations that require invasive cardiac procedures or support with an intra-aortic balloon pump can be unsettling. This study was undertaken to measure the effect of a music intervention on physiologic and psychological responses of patients on bed rest due to procedural sheaths or an intra-aortic balloon pump. A randomized, two-group, pretest/post-test design was utilized to measure the effect of a 30-minute music intervention on heart rate, blood pressure, respiratory rate, skin temperature, pain perception, and mood states. One hundred forty subjects participated, 65 in the control group and 75 in the treatment group. There were no significant differences between the groups in demographic, clinical, or baseline variables, except for respiratory rate. After the music intervention, there were reductions in blood pressure, respiratory rate, and psychological distress, as measured by the Profile of Mood States (p < 0.05). Music appeared to affect selected physiologic responses and reduce psychological distress in patients on bed rest.", "The addition of self-selected music as a conditioning aid during prepared childbirth education and subsequent family performance in labor within a musical environment were examined. Thirty primigravida couples received the same psychoprophylactic instruction, with 15 randomly selected couples receiving the added musical conditioning aid. Medication use remained minimal, without significant difference, for couples who did and couples who did not use music. However, the value of music to both the family and the health care staff is felt to be of enough subjective significance to warrant its use as a normal component of prepared childbirth education.", "The purpose of this study was to examine the effects of music on elevated state of anxiety as many patients become stressed and anxious during diagnostic procedures. The study was conducted on 104 consecutive patients undergoing GI endoscopy for various reasons. Patients were randomly assigned to two groups regardless of sex, age and underlying disease. One group of 54 patients were made to listen to a recorded Indian classical instrumental music before and during the procedure, while the other group of 50 patients did not. Blood pressure, heart rate and respiratory rate were recorded at the beginning of consultation and end of procedure. Perception of procedure using a three point attitude scale was assessed. Our results indicate that the background Indian classical music is efficacious in reducing psychological distress during a gastroscopic examination. We suggest that music could be applied to other medical situations as well, which tend to generate undue psychological stress and anxiety. Music, as a familiar personal and culture medium, can be used to ease anxiety, to act as distractor, to increase discomfort and pain threshold.", "Osteoarthritis is the most common degenerative disease in humans. It usually begins in middle age and is progressive. Chronic pain in older people presents a significant obstacle in maintaining function and independence. Previous studies have shown that music can improve motivation, elevate mood, and increase feelings of control in older people.\n The purpose of this randomized clinical trial was to examine the influence of music as a nursing intervention on osteoarthritis pain in elders.\n Data were collected using the short form of the McGill Pain Questionnaire with 66 elders suffering from chronic osteoarthritis pain. Differences in perceptions of pain were measured over 14 days in an experimental group who listened to music for 20 minutes daily and a control group who sat quietly for 20 minutes daily. All participants completed the Short Form McGill Pain Questionnaire (SF-MPQ) on day 1, 7, and 14 of the study.\n Results of t-tests indicated that those who listened to music had less pain on both the Pain Rating Index on day 1 (P = 0.001), day 7 (P = 0.001) and day 14 (P = 0.001) and on the Visual Analogue Scale on day 1 (P = 0.001), day 7 (P = 0.001) and day 14 (P = 0.001), when compared with those who sat quietly and did not listen to music. A repeated measure analysis of variance controlling for pretest measures demonstrated a significant decrease in pain among experimental group participants when compared with the control group on the pain descriptor section of the SF-MPQ (P = 0.001) and the visual analogue portion of the SF-MPQ (P = 0.001).\n Listening to music was an effective nursing intervention for the reduction of chronic osteoarthritis pain in the community-dwelling elders in this study.", "The aim of this randomized controlled trial was to determine the effect of jaw relaxation, music and the combination of relaxation and music on postoperative pain after major abdominal surgery during ambulation and rest on postoperative days 1 and 2. Opioid medication provided for pain, following abdominal surgery, does not always give sufficient relief and can cause undesired side effects. Thus, additional interventions such as music and relaxation may provide more complete relief. Previous studies have found mixed results due to small sample sizes and other methodological problems. In a rigorous experimental design, 500 subjects aged 18-70 in five Midwestern hospitals were randomly assigned by minimization to a relaxation, music, relaxation plus music, or control group. Interventions were taught preoperatively and tested postoperatively. The same amount of time was spent with subjects in the control group. Pain was measured with the visual analogue sensation and distress of pain scales. Demographic and surgical variables, and milligrams of parenteral or oral opioids in effect at the time of testing were not significantly different between the groups, nor did they correlate with pain scores. Controlling for pretest sensation and distress, orthogonal a priori contrasts and multivariate analysis of covariance indicated that the three treatment groups had significantly less pain than the controls, (P = 0.028-0.000) which was confirmed by the univariate analysis of covariance (P = 0.018-0.000). Post hoc multivariate analysis revealed that the combination group had significantly less sensation and distress of pain than the control group on all post-tests (P = 0.035-0.000), and the relaxation and music groups had significantly less on all tests (P = 0.022-0.000) except after ambulation. At post ambulation those using relaxation did not have significantly less pain than the controls on both days and those using music did not on day 1, although there were some univariate effects. A corresponding significant decrease in mastery of the interventions from pre to post ambulation suggests the need for reminders to focus on the intervention during this increased activity. Physicians and nurses preparing patients for surgery and caring for them afterward, should encourage patients to use relaxation and music as adjuvants to medication for postoperative pain.", "This study examined the effect of music on pain, hemodynamic variables, and respiration in the PACU, and the impact of music on patients' recall of their PACU experience. Sixty patients scheduled for thyroid, parathyroid, or breast surgery under general anesthesia were studied. Patients were randomly assigned into three groups: group 1, control, not wearing headphones; group 2, wearing headphones but hearing no music; and group 3, wearing headphones and listening to music. A visual analogue pain scale was used to rate patients' perception of pain. There was no difference in pain level, morphine requirement, hemodynamics, respiration, or length of stay in the PACU among the 3 groups, yet the music group was able to wait significantly longer before requiring analgesia on the nursing unit. Patients who listened to music perceived their PACU experience as significantly more pleasant than the patients in the other two groups as recalled both 1 day and 1 month later.", "This study was designed to determine whether music or music in combination with therapeutic suggestions in the intra-operative period under general anaesthesia could improve the recovery of hysterectomy patients.\n In a double-blind randomised clinical investigation, 90 patients who underwent hysterectomy under general anaesthesia were intra-operatively exposed to music, music in combination with therapeutic suggestion or operation room sounds. The anaesthesia was standardised. Postoperative analgesia was provided by a patient-controlled analgesia (PCA). The pain scores were recorded by means of a visual analogue scale. Nausea, emesis, bowel function, fatigue, well-being and duration of hospital stay were studied as outcome variables.\n On the day of surgery, patients exposed to music in combination with therapeutic suggestions required less rescue analgesic compared with the controls. Patients in the music group experienced more effective analgesia the first day after surgery and could be mobilised earlier after the operation. At discharge from the hospital patients in the music and music combined with therapeutic suggestion group were less fatigued compared to the controls. No differences were noted in nausea, emesis, bowel function, well-being or length of hospital stay between the groups.\n This double-blind study has demonstrated that intra-operative music and music in combination with therapeutic suggestions may have some beneficial effects on postoperative recovery after hysterectomy. Further controlled studies are necessary to confirm our results.", "The purpose of this study was to investigate the effects of audiotaped lullabies on physiological and behavioral distress and perceived pain among children during routine immunization. An experimental design was used to study 99 healthy children ages 3 to 6 years. Half the children received the musical intervention during the immunizations, while the other half did not. Groups were assessed during five phases: baseline, preimmunizations, during the immunization, after Band-Aid application, and 2 min after phase 4. Physiological variables (heart rate, blood pressure) were obtained in phases 1, 4, and 5. Behavioral distress was measured using the Observational Scale of Behavioral Distress during phases 1, 2, 3, and 4. Pain perception was measured using the Oucher in phases 1 and 4. No significant differences were found between experimental and control groups for heart rate, blood pressure, or Oucher scores. However, total distress scores were significantly less for the experimental group. These results indicate that immunization is a stressful experience for children. Recommendations include further study incorporating pharmacological and nonpharmacological interventions.", "The possible antinociceptive effect of hemispheric-synchronised sounds, classical music and blank tape were investigated in patients undergoing surgery under general anaesthesia. The study was performed on 76 patients, ASA 1 or 2, aged 18-75 years using a double-blind randomised design. Each of the three tapes was allocated to the patients according to a computer-generated random number table. General anaesthesia was standardised and consisted of propofol, nitrous oxide 66%/oxygen 33%, isoflurane and fentanyl. Patients breathed spontaneously through a laryngeal mask and the end-tidal isoflurane concentration was maintained near to its minimum alveolar concentration value of 1.2%. Fentanyl was given intravenously sufficient to keep the intra-operative heart rate and arterial blood pressure within 20% of pre-operative baseline values and the fentanyl requirements were used as a measure of nociception control. Patients to whom hemispheric-synchronised sounds were played under general anaesthesia required significantly less fentanyl compared with patients listening to classical music or blank tape (mean values: 28 microgram, 124 microgram and 126 microg, respectively) (p < 0.001). This difference remained significant when regression analysis was used to control for the effects of age and sex.", "Registration of the influence of musical rhythm on synchronisation and coordination of heart rate.\n Randomized pilot study. PROBANDS: 28 patients with chronic cancer pain in a stable phase of the disease. Intervention:14-day training of a relaxation therapy designed for improving the falling asleep, including a 30-minute lullaby-like, rhythmically dominated music with gradually decreasing tempi. No training in the control group.\n Continuous registration of heart rate and comparison with musical beat on day 1 and 15. Analysis of the degree of synchronisation, i.e. the coordination of systole and musical central time point (1st beat of the 6/8 time alla breve). Recording of the time of falling asleep and registration of the patient's subjective evaluation of the relaxation therapy and the pain intensity using verbal rating scales. Documentation of the use of analgetics.\n Under the relaxation therapy trained patients showed an increasing synchronisation and coordination of heart rate and musical beat. At a musical tempo between 48 and 42 beats per min a very stable 2 : 3 synchronisation occurred. Trained patients who reported the best relaxing and analgetic effects showed the highest degree of synchronisation. Relaxation therapy led to an improvement of falling asleep and to a decrease in consumption of analgetics.\n Lullaby-like music within a special range of tempi can induce a trainable synchronisation of heart rate, functionally associated with the formation and intensity of a relaxation reaction. Further investigations are promising, however, substantial improvements in the measurement and documentation methods are needed.", "Management of pain in the immediate postoperative period is a major concern of postanesthesia nurses. Music is a nursing intervention with the potential to decrease patient perception of pain in the PACU. The purpose of this study was to examine the effect of the use of music on the level of patient pain in the immediate postoperative period. A quasi-experimental study design was used with three study groups. All patients scheduled for elective abdominal hysterectomies using a general anesthesia technique were eligible for participation in the study. The setting is a PACU in a community hospital in a suburban area. Subjects were asked to rate their pain level every 15 minutes while in the PACU using two valid and reliable measures, a verbal pain rating scale and a graphic numeric pain intensity scale. Repeated measures of analysis of variance showed no differences in level of pain between groups or over time.", "This study tested the efficacy of 2 brief cognitive interventions in supplementing regular medical treatment for pain during burn dressing change. Forty-two burn inpatients were randomly assigned to 3 groups: sensory focusing, music distraction, and usual care. Patients reported pain, pain relief satisfaction with pain control, and pain coping strategies. The sensory focusing group reported greater pain relief compared to the music distraction group and a reduction in remembered pain compared to the usual care group, although group differences were not observed on serial pain ratings. In addition, after controlling for burn size and relevant covariates, regression analyses indicated that catastrophizing predicted pain, memory for pain, and satisfaction with pain control. Refinement of the sensory focusing intervention is warranted to reduce catastrophic thinking and improve pain relief", "The purpose of this experimental crossover study was to evaluate to what extent the therapeutic use of music would decrease pain in patients with cancer who were receiving scheduled analgesics. Baseline data were collected for three days. Subjects then were assigned randomly to listen to their preference of seven types of relaxing music or a control (a 60-cycle hum) twice daily for three days. Then they crossed over into the alternate group for the next three days. Finally, each subject returned to a follow-up baseline period. Pain, the dependent variable, and mood, which was proposed as an intervening variable, were measured by visual analogue scales. The convenience sample included 15 outpatients with cancer, 12 female and 3 male, ages 20 through 87. Results of the McGill Pain Questionnaire (MPQ), a reliable and valid multidimensional instrument administered upon entry into the study, indicated that the study sample was comparable to other samples of patients with cancer who were in pain. There was an inconsistent relation between pain and mood. The effect of the music on pain varied by individual; 75% had at least some response and 47% had a moderate or great response. Multivariate Analysis of Variance (MANOVA) indicated a statistically significant decrease in pain from using either the music or sound, but there was no effect on mood. Although the mean percentage of change in pain for music was twice that for sound, the results did not differ statistically. The findings support the use of music as an independent nursing intervention to relieve pain.", "This study was designed to determine whether music (M), or music in combination with therapeutic suggestions (M/TS) could improve the postoperative recovery in the immediate postoperative in daycare surgery.\n One-hundred and eighty-two unpremedicated patients who underwent varicose vein or open inguinal hernia repair surgery under general anaesthesia were randomly assigned to (a). listening to music (b). music in combination with therapeutic suggestions or (c). blank tape in the immediate postoperative period. The surgical technique, anaesthesia and postoperative analgesia were standardized. Analgesia, the total requirement of morphine, nausea, fatigue, well-being, anxiety, headache, urinary problems, heart rate and oxygen saturation were studied as outcome variables.\n Pain intensity (VAS) was significantly lower (P = 0.002) in the M (2.1), and the M/TS (1.9) group compared with the control group (2.9) and a higher oxygen saturation in M (99.2%) and M/TS (99.2%) group compared with the control (98.0%), P < 0.001, were found. No differences were noted in the other outcome variables.\n This controlled study has demonstrated that music with or without therapeutic suggestions in the early postoperative period has a beneficial effect on patients' experience of analgesia. Although statistically significant, the improvement in analgesia is modest in this group of patients with low overall pain levels.", "To examine the effect of listening to self-selected music versus an intradermal injection of normal saline solution on the intensity and distress of intravenous (IV) catheter insertion pain.\n Prospective, randomized, controlled study.\n Inpatient and outpatient units in 2 university-affiliated southwestern medical centers.\n One hundred ten adult inpatients and outpatients undergoing IV therapy. Outcome Measures: Pain intensity, pain distress, and IV insertion difficulty visual analog scales.\n Patients were randomly assigned to receive an intradermal injection of normal saline solution, listen with headphones to self-selected music, or be in a control group for IV insertion.\n A MANOVA revealed no statistically significant multivariate or univariate differences in pain by treatment group, but significantly higher pain distress scores with failed IV insertions. The pain intensity and distress scores were significantly higher in the saline solution group when compared with the music and control groups combined. Insertion difficulty was significantly positively correlated with pain intensity and distress for the entire sample, with weak, nonsignificant correlations in the music group.\n Intradermal unpreserved saline solution contributes to greater pain intensity and distress, greater insertion difficulty, and a higher failure rate than the use of music or routine IV insertion. Listening to preferred music attenuates the effect of insertion difficulty on IV insertion pain. Intravenous insertion attempts were unsuccessful in more than one third of the subjects, resulting in higher pain distress scores. Further research is needed on interventions to reduce IV insertion pain and on factors contributing to IV insertion failure.", "The purpose of this study was to determine the effect of some noninvasive pain reduction interventions on pain in 121 neonates undergoing unanesthetized circumcision. Subjects were randomly assigned to one of six groups: classical music, intrauterine sounds, pacifier, music and pacifier, intrauterine sounds and pacifier, or control (no nurses present and no pain reduction interventions used). Physiological variables that were monitored were heart rate, rhythm, dysrhythmias, blood pressure, transcutaneous oxygen (tcpO2), rate pressure product, and behavioral state, measured during 14 circumcision steps. Over the 14 steps, 42% of the heart rates, 78% of the systolic blood pressures (SBP), 30% of the diastolic blood pressures (DBP), and 81% of the tcpO2 pressures were abnormal. Few significant differences were found among any of the steps. SBP and DBP differed significantly between groups during two of the noninvasive steps; and tcpO2 differed significantly during six steps.", "The effect of intra-operative compared to postoperative music on postoperative pain was evaluated in a controlled trial. In all, 151 patients undergoing day case surgery for inguinal hernia repair or varicose vein surgery under general anaesthesia were randomly allocated to three groups: group 1 listened to music intra-operatively, group 2 listened to music postoperatively and group 3, the control group, listened to 'white noise'. The anaesthetic and postoperative analgesic techniques were standardised. Pain was assessed using a numeric rating scale (0-10) and patients requirements for postoperative morphine, paracetamol and ibuprofen was recorded. The effect of music on nausea, fatigue and anxiety was also investigated. The results showed that patients exposed to music intra-operatively or postoperatively reported significantly lower pain intensity at 1 and 2 h postoperatively and patients in the postoperative music group required less morphine at 1 h compared to the control group. No differences were noted in the other variables. This study demonstrates that there is a short-term pain-reducing effect of music therapy however, the beneficial effects do not differ if the patient is exposed to music intra-operatively or postoperatively.", "To evaluate the impact of music on opioid requirements and pain levels during renal lithotripsy using alfentanil patient-controlled analgesia (PCA), we conducted a prospective, blinded, randomized controlled trial. Patients undergoing lithotripsy were instructed in PCA use and asked to rate their anxiety and select their preferred type of music. They were then premedicated with morphine and ketorolac and randomly allocated into two groups. Group 1 (n = 97) had music started 10 min before the procedure and maintained until 10 min after its conclusion. Group 2 (n = 96) had music begun at the conclusion of lithotripsy and continued for 10 min. Pain intensity, alfentanil requirement, side effects, quality of analgesia, patient satisfaction, and acceptance of the technique were evaluated. Demographics, alfentanil requirement, pain levels, side effects, quality of analgesia, and patient satisfaction were similar in both groups. The addition of music did not provide any benefit. This result raises the possibility that some nonpharmacologic therapies have minimal impact in settings where the painful stimulus is moderate to severe and adequate pharmacotherapy is available.", "Several pharmacological interventions reduce perioperative stress hormone release during surgery under general anesthesia. Listening to music and therapeutic suggestions were also studied, but mostly in awake patients, and these have a positive effect on postoperative recovery and the need for analgesia. In this study, we evaluated the effect of listening to music under general anesthesia on the neurohormonal response to surgical stress as measured by epinephrine, norepinephrine, cortisol, and adrenocorticotropic hormone (ACTH) blood levels. Thirty female patients scheduled for abdominal gynecological procedures were enrolled and randomly divided into two groups: group NM (no music) and group M (music). In group M, music was played from after the induction of anesthesia until the end of surgery. In the NM group, the patients wore the headphones but no music was played. We established three sample times for hormonal dosage during the procedure and one in the recovery room. Hemodynamic data were recorded at all times, and postoperative consumption of morphine in the first 24 h was noted. There was no group difference at any sample time or in the postoperative period in terms of mean arterial blood pressure, heart rate, isoflurane end-tidal concentration, time of the day at which the surgery was performed, bispectral index (BIS) value, doses of fentanyl, or consumption of postoperative morphine. There was no difference between the two groups with regard to plasmatic levels of norepinephrine, epinephrine, cortisol, or ACTH at any sample time, although the blood level of these hormones significantly increased in each group with surgical stimulation. In conclusion, we could not demonstrate a significant effect of intraoperative music on surgical stress when used under general anesthesia.\n Listening to music under general anesthesia did not reduce perioperative stress hormone release or opioid consumption in patients undergoing gynecological surgery.", "Immediately before they underwent femoral angiography, 45 patients were given one of three types of audiotapes: a relaxation response tape recorded for this study, a tape of contemporary instrumental music, or a blank tape. All patients were instructed to listen to their audiotape during the entire angiographic procedure. Each audiotape was played through earphones. Radiologists were not told the group assignment or tape contents. The patients given the audiotape with instructions to elicit the relaxation response (n = 15) experienced significantly less anxiety (P less than .05) and pain (P less than .001) during the procedure, were observed by radiology nurses to exhibit significantly less pain (P less than .001) and anxiety (P less than .001), and requested significantly less fentanyl citrate (P less than .01) and diazepam (P less than .01) than patients given either the music (n = 14) or the blank (n = 16) control audiotapes. Elicitation of the relaxation response is a simple, inexpensive, efficacious, and practical method to reduce pain, anxiety, and medication during femoral angiography and may be useful in other invasive procedures.", "Pain associated with chest tube removal is a major problem for patients who undergo open heart surgery. Because this pain is short-lived, timing the administration of pharmacological agents for pain relief is difficult and is therefore done inconsistently.\n To examine the effect of music as an intervention for pain relief during chest tube removal after open heart surgery.\n In an experimental design, 156 subjects (mean age, 66 years; 69% men) were randomly assigned to 1 of 3 groups: control, white noise, or music. All subjects preselected the type of music they preferred hearing. Ten minutes before the chest tube was removed, the patient's heart rate and blood pressure were measured, the patient rated pain intensity by using a numeric rating scale, and the prerecorded audiotape of music was begun. The patients rated their pain again immediately after chest tube removal and 15 minutes later. Physiological variables were assessed every 5 minutes until 15 minutes after the chest tubes were removed.\n Self-reported pain intensity, physiological responses, and narcotic intake after chest tube removal did not differ significantly among the 3 groups.\n Although the findings were not statistically significant, most subjects enjoyed listening to the music, and therefore the use of music as an adjuvant to other therapies may be an appropriate nursing intervention.", "The goal of this work was to investigate the impact of music on women's anxiety and perceived pain during colposcopy examination.\n This was a prospective randomized study. Two hundred and twenty women referred for colposcopy for the first time were recruited. They were randomized to either the music or no-music group. Before colposcopy examination, each subject completed a Chinese version of the state anxiety questionnaire (STAI) and assessed the anticipated pain for colposcopy with a visual analog scale (VAS). Slow-rhythm music was played during colposcopy examination in the music group. Subjects in the no-music group were examined in the same setting without music. After colposcopy, each subject completed the STAI form again and assessed their pain during examination by the VAS.\n Women in the music group experienced significantly less pain (mean VAS 3.32 [95% CI 2.86-3.78] vs 5.03 [4.54-5.52], P<0.001) and lower anxiety (mean STAI 39.36 [95% CI 37.33-41.39] vs 44.16 [41.82-46.49], P = 0.002) during colposcopy examination than women in the no-music group. On linear regression analysis, the factors significantly affecting anxiety during colposcopy were anxiety score at enrollment, pain score during colposcopy, and whether or not the women had listened to music during the colposcopy examination. The factors significantly affecting the pain scores were whether the women had listened to music during the procedure and the final anxiety scores.\n Music is a simple, inexpensive, and easily used strategy to minimize anxiety and pain during colposcopy examination.", "Two studies were conducted to examine the effects of music on analogued labor pain using volunteer nulliparous subjects who were randomly assigned to treatment groups (n = 10 per group). Assessments of the treatments were made in a 1-hour session involving twenty 80-second exposures to a laboratory pain stimulus patterned to resemble labor contractions. In the first experiment, it was hypothesized that subjects listening to easy-listening music would report lower pain ratings and cardiovascular responses than subjects listening to rock music, self-selected music, or a dissertation (placebo-attention) and subjects in a no-treatment control group. No significant group effects were found; significant time effects were found for heart rate, systolic and diastolic blood pressure. Subjects spontaneously reported using imagery as a pain reduction technique. In the second study a combination of music and imagery was examined by randomly assigning subjects to one of five groups: self-generated imagery with music (SIM), guided imagery with music (GIM), self-generated imagery without music (SI), guided imagery without music (GI), or no-treatment control. Again, no significant group effects were obtained. Significant time effects were obtained for heart rate, systolic and diastolic blood pressure.", "Labor pain is often severe, and analgesic medication may not be indicated. In this randomized controlled trial we examined the effects of music on sensation and distress of pain in Thai primiparous women during the active phase of labor. The gate control theory of pain was the theoretical framework for this study. Randomization with a computerized minimization program was used to assign women to a music group (n = 55) or a control group (n = 55). Women in the intervention group listened to soft music without lyrics for 3 hours starting early in the active phase of labor. Dual visual analog scales were used to measure sensation and distress of pain before starting the study and at three hourly posttests. While controlling for pretest scores, one-way repeated measures analysis of covariance indicated that those in the music group had significantly less sensation and distress of pain than did the control group (F (1, 107) = 18.69, p <.001, effect size =.15, and F (1, 107) = 14.87, p <.001, effect size =.12), respectively. Sensation and distress significantly increased across the 3 hours in both groups (p <.001), except for distress in the music group during the first hour. Distress was significantly lower than sensation in both groups (p <.05). In this controlled study, music--a mild to moderate strength intervention--consistently provided significant relief of severe pain across 3 hours of labor and delayed the increase of affective pain for 1 hour. Nurses can provide soft music to laboring women for greater pain relief during the active phase when contractions are strong and women suffer.", "Administration of sedatives and analgetics during colonoscopy includes the risk for arterial hypotension and respiratory depression. The aim of this study was to assess whether music therapy increases patients tolerance and reduces the need of analgo-sedative premedication.\n 146 consecutive patients were examined in a randomized, prospective study. Colonoscopy was performed under intravenous administration with titrated dosages of midazolam and pethidin. Oxygen was given in cases of blood desaturation below values of 90%. Patients younger than 18 and older than 80 years, patients with history of partial colectomy, gastrectomy or hysterectomy and patients with colonic tumorous or inflammatory stenosis were excluded. 60 patients underwent conventional procedure (Group A), whereas 59 patients received additional music therapy (Group B). Time required to reach the cecum (examination time) was measured and the rate of successful colonoscopies was determined.\n Most of the patients required sedation with midazolam in both groups (97 vs. 93%), whereas more group A patients required analgesia with pethidin than group B patients (43 vs. 31%, p<0.05). Under music therapy the rate of completed colonoscopies was higher (group A 93%, group B 98%) and examination time was significantly accelerated (group A 22.8 +/- 14.6 min, group B 16.8 +/- 11.8 min, p<0.03).\n Accompanying music therapy reduces requirement of analgesia during colonoscopy, favours completion of the procedure and shortens examination time. Music therapy seems to promote safer conditions for endoscopical practice and diminishs patients discomfort.", "To test the effect of nonnutritive sucking (NNS), music therapy (MT), and combined NNS and MT (NNS + MT), versus no intervention, on heart rate, transcutaneous oxygen (TcPaO(2)) levels, and pain behavior of neonates in intensive care units having blood taken by a heel-stick procedure.\n A within-subjects, counter-balancing, repeated-measures design conducted in a government-funded hospital in Hong Kong, comparing TcPaO(2) levels, heart rate, and pain behavior outcomes in 27 neonates.\n Repeated-measures multivariate analysis of variance revealed statistically significant differences in outcomes across all interventions (Wilk's lambda =.142; F [3,27] = 31.82; eta2 =.47). One-way analysis of variance revealed that the 3 comfort interventions significantly reduced neonates' heart rate (Wilk's lambda =.647; F [2,27] = 18.93; eta2 =.35), improved their TcPaO(2) levels (Wilk's lambda =.481; F [2,27] = 37.42; eta2 =.51), and reduced their pain behavior (Wilk's lambda =.312; F [2,27] = 76.42; eta2 =.68). Posthoc scheffe tests revealed that NNS + MT had the strongest effect on neonates' TcPaO(2) levels and pain behavior; MT alone had the strongest effect on neonates' heart rate.\n Health professionals using NNS + MT when doing heel-sticks can improve the TcPaO(2) levels of neonates and reduce their pain. Using MT alone can improve the heart rate of neonates.", "The purpose of this experimental study was to determine the effects of second and third day postoperative music interventions (music, music video) on pain and sleep in 96 postoperative patients having CABG surgery. The Verbal Rating Scale scores obtained before and after each 30-minute session showed that pain decreased over time for all three groups with no difference across groups. The McGill Pain Questionnaire (MPQ) was administered before session 1 and after session 2, and results indicated that Sensory, Affective, and Present Pain Intensity subscales showed no group difference for pain; however, pain decreased from Day 2 to Day 3 for all three groups. For the evaluative component of pain, those in the music group had significantly (F[2,93] = 4.74, p < .05) lower scores on postoperative Day 2 than the rest period control group. Effects of the intervention on sleep as measured by the Richard Sleep Questionnaire indicated that the video group had significantly (F[2, 92] = 3.18, p < .05) better sleep scores than the control group on the third morning. These findings lend some support for selected music interventions.", "To evaluate the efficacy of music on sedation in extracorporeal shock wave lithotripsy (ESWL) treatment to compare its anxiolytic effects with those of midazolam.\n Ninety-eight urolithiasis patients were randomly divided into two groups. Hemodynamic parameters, including mean arterial pressure, heart rate, respiration rate, and oxygen saturation, were recorded in all patients. In 50 patients (group 1), 2 mg of midazolam was administered intravenously 5 minutes before ESWL. In group 2 (n = 48), music chosen by the patients was listened to with a headset and continued during the treatment. The visual analog scale (0 to 100 mm), Observer's Assessment of Alertness/Sedation Scale, State and Trait Anxiety Inventory-Trait Anxiety test, and State and Trait Anxiety Inventory-State Anxiety test were administered for the evaluation of pain, sedation level, and patient anxiety.\n For the hemodynamic parameters, a statistically significant decrease in mean arterial pressure was noted at the end of the ESWL procedure in group 2 and in oxygen saturation from the 10th minute to the end of the treatment in group 1. Although the visual analog scale, Observer's Assessment of Alertness/Sedation Scale, and State and Trait Anxiety Inventory-State Anxiety test did not show statistically significant differences, the State and Trait Anxiety Inventory-Trait Anxiety score was found to be lower in the music group (group 2) than in the midazolam group (group 1).\n With the anxiolytic effects of music, ESWL can be performed more effectively with the patient in a comfortable state. Listening to music by patients during the ESWL session is a feasible and convenient alternative to sedatives and anxiolytics.", "The purpose of the study was to determine the efficacy of music and eutectic mixture of local anesthetics (EMLA) on pain responses of neonates undergoing circumcision.\n A randomized, double-blind experimental design was used with 23 neonates. Pain response was measured using an observational pain intensity rating scale and the physiologic parameters of heart rate, respiratory rate, oxygen saturation levels, salivary cortisol levels, and length of cry. Each infant's state was examined for a potential contribution to the pain response.\n Infant state, salivary cortisol levels, and respiratory rates were not significant. Pain ratings had considerable variability for all treatment conditions, but both single treatment groups had less pain by the end of the procedure. The heart rate was significantly lower for the EMLA group and remained stable for the music group. Oxygen saturation differences were statistically significant for the music group (P =.02) and approached significance for the EMLA group.\n Preliminary support was provided for the efficacy of EMLA and music to contribute to the pain relief of neonates undergoing circumcision. Further study is warranted. Neonates deserve interventions that will provide them with a less painful start in life.", "Music is a method nurses can use to help relieve pain, however little is known about its effectiveness across cultures. In this study, Western music was tested for its effectiveness in reducing postoperative pain in 38 Taiwanese patients, and its acceptability was explored. A pretest and post-test experimental design was used with visual analogue scales to measure sensation and distress of pain. Before surgery, subjects were randomly assigned to receive tape recorded music or the usual care. Those who were assigned to the music group chose among 5 types of sedative music. On postoperative Day 1 and Day 2, the effectiveness of the tape-recorded music was investigated during 15 minutes of rest in bed. Patients were interviewed on Day 3 to determine their liking for the music, its calming effects, and the helpfulness of the music. Repeated measures analysis of variance showed a significant interaction between time and group in the distress of pain on Day 1, but not on Day 2, and in pain sensation on Day 2, but not Day 1. Subjects from Taiwan were similar to subjects in a previous study in the United States in their liking for the music, and in reports of the helpfulness of the music for pain sensation and distress, but fewer Taiwanese found the music calming, and they had different choices: more chose harp music and fewer chose jazz than subjects in the U.S. study, and some would prefer Buddhist hymns or popular songs heard in Taiwan. Findings support the use of culturally acceptable music in addition to analgesic medication for the sensation and distress of postoperative pain.", "To determine the effect of two comfort interventions during unanesthesized circumcision on neonatal pain.\n Fifty-eight neonates were randomly assigned to one of three intervention groups. Eighteen control infants received routine care, 15 infants had music played, and 15 infants had a tape of intrauterine sounds played. During circumcision, monitors measured cardiac rate, rhythm, blood pressure, and transcutaneous oxygen. Pain was measured by analysis of videotaped facial expressions using Izard's Maximally Discriminative Facial Movement Coding System (1983).\n Mean heart rate was above normal limits during all steps of the circumcision for the control group and during some of the steps for the other two groups. Facial expressions analyzed showed all three groups had pain much more than any other emotion during the procedure.\n The two interventions were unable to offset the effects of circumcision pain.", "A prospective randomized controlled trial was performed to test the hypotheses that music decreases the dose of sedative medication required for colonoscopy and that the combination of music and patient-controlled sedation improves patient acceptance of colonoscopy.\n One hundred sixty-five patients scheduled to undergo elective colonoscopy were randomized to receive 1 of 3 different modes of sedation: Group 1, a combination of music and patient-controlled sedation with a mixture of propofol and alfentanil; Group 2, patient-controlled sedation alone; Group 3, music alone with diazemuls and meperidine administered intravenously if requested by the patient. Each bolus of patient-controlled sedation delivered 4.8 mg propofol and 12 microg alfentenil. Music was provided by means of a portable compact disc machine with headphones. Outcome measures assessed immediately after colonoscopy and 24 hours later included dose of patient-controlled sedation used, complications, recovery time, pain score, satisfaction score, and willingness to repeat the procedure with the same mode of sedation.\n The mean (SD) dose of propofol used in Group 1 was significantly less than Group 2 (0.84 mg/kg [0.69 mg/kg] vs. 1.15 mg/kg [0.83 mg/kg]; p = 0.02, t test). The mean (SD) satisfaction score was higher in Group 1 (7.8 [2.1]) compared with Group 2 (6.8 [2.3]) and Group 3 (7.4 [2.3]) (p = 0.05, 1-way analysis of variance). The majority of patients in Group 1 were willing to repeat the same mode of sedation when queried immediately after colonoscopy (87%) and 24 hours later (75%), which was significantly different from the corresponding results in the other 2 groups; p = 0.04 and p < 0.01 respectively, chi-square test.\n Music can decrease the dose of sedative medication required for colonoscopy. The combination of music and patient-controlled sedation was the best-accepted mode of sedation among 3 groups.", "A randomized, single-blinded, placebo-controlled trial examined the benefits of taped therapeutic suggestions and taped music in coronary-artery-bypass patients. Sixty-six patients listened to either suggestion tapes or music tapes, intraoperatively and postoperatively; 29 patients listened to blank tapes intraoperatively and listened to no tapes postoperatively. Half the patients who listened to a tape found it helpful. There were no significant differences between groups in length of SICU or postoperative hospital stay, narcotic usage, nurse ratings of anxiety and progress, depression, activities of daily living, or cardiac symptoms. There were no significant differences in these same outcomes between the patients who were helped by the tapes and the patients not helped. These results suggest that if taped therapeutic suggestions have a measurable effect upon cardiac surgery patients, demonstrating this effect will require more detailed patient evaluations to identify subgroups of patients responsive to this type of intervention.", "This experimental study compared the effects of jaw relaxation and music, individually and combined, on sensory and affective pain following surgery. Abdominal surgical patients (N = 84) were randomly assigned to four groups: relaxation, music, a combination of relaxation and music, and control. Interventions were taught preoperatively and used by subjects during the first ambulation after surgery. Indicators of the sensory component of pain were sensation and 24-hour narcotic intake. Indicators of the affective component of pain were distress and anxiety of pain. With preambulatory sensation, distress, narcotic intake, and preoperative anxiety as covariates, the four groups were compared using orthogonal a priori contrasts and analysis of covariance. The interventions were neither effective nor significantly different from one another during ambulation. However, after keeping the taped interventions for 2 postoperative days, 89% of experimental subjects reported them helpful for sensation and distress of pain.", "Screening flexible sigmoidoscopy (FS) is an effective tool for the detection of colon cancer. Nonetheless, persons are reluctant to undergo FS for a variety of reasons such as anxiety, discomfort, and the possibility of abnormal findings. Nurses caring for FS patients can implement interventions to allay anxiety and promote comfort in an effort to enhance satisfaction and future compliance. Music therapy is one nonpharmacologic intervention that has been shown to be effective in allaying anxiety, reducing discomfort, and promoting satisfaction in other patient populations. A two-group pretest, posttest experimental design with repeated measures study recruited 64 subjects undergoing FS from one Midwestern tertiary care center. Subjects were randomly assigned to a control condition of usual procedural care or to an experimental condition of music therapy during the examination. State and trait anxieties were measured at pretest. State anxiety, discomfort, satisfaction, and perceived compliance with future screening were measured after the procedure. Subjects in the music group reported less anxiety and discomfort than subjects in the control group. There were no differences on satisfaction ratings or perceived compliance with screening guidelines. Nurses caring for patients undergoing screening FS can offer music therapy as one nonpharmacologic intervention to ameliorate anxiety and reduce discomfort.", "nan" ]

[ "16890599", "16618403", "18069698", "18046717", "20683847" ]

[ "Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment.", "Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin.", "Individualized treatment duration for hepatitis C genotype 1 patients: A randomized controlled trial.", "Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis c genotype 1-infected slow responders.", "Randomized trial of peginterferon alfa-2b and ribavirin for 48 or 72 weeks in patients with hepatitis C virus genotype 1 and slow virologic response." ]

[ "Patients with chronic hepatitis C who do not respond rapidly to therapy have a low chance of developing a sustained virologic response (SVR) when treated for 48 weeks. This study investigated whether treatment for 72 weeks increases the rate of SVR in patients with detectable hepatitis C virus (HCV)-RNA levels at week 4 of treatment.\n A total of 510 treatment-naive patients were treated with peginterferon-alfa2a (180 microg/wk) plus ribavirin (800 mg/day). Patients with detectable HCV-RNA levels at week 4 (n = 326) were randomized to complete 48 (group A, n = 165) or 72 weeks (group B, n = 161) of treatment. Patients with undetectable HCV-RNA levels at week 4 (n = 184) were allocated into group C (n = 148) or group D (n = 36), according to HCV genotype and baseline viremia, and treated for 24 or 48 weeks, respectively. All patients were followed-up for 24 weeks after the end of treatment.\n The end-of-treatment response rate (61%) was similar in groups A and B, but the SVR rate was higher in group B (45% vs 32% in A; P = .01). In genotype 1-infected patients randomized to group A (n = 149) or B (n = 142), SVR rates were 28% and 44%, respectively (P = .003). The incidence of adverse events was similar in all groups. Treatment discontinuation was more frequent in group B (36%) than in group A (18%) (P = .0004). SVR rates in groups C and D were 79% and 64%, respectively.\n Extension of treatment with peginterferon-alfa2a plus ribavirin from 48 to 72 weeks significantly increases the rate of SVR in patients with detectable viremia at week 4 of treatment.", "The treatment of patients infected with hepatitis C virus (HCV) type 1 remains a challenge necessitating innovative strategies to improve treatment outcome. The extension of treatment duration beyond 48 weeks is one possible strategy to address this problem.\n The efficacy and safety of 48 weeks (group A, N = 230) vs 72 weeks (group B, N = 225) of treatment with pegylated-interferon-alfa-2a (180 microg/wk) plus ribavirin (800 mg/day) were studied in treatment-naive patients with HCV type 1 infection. On-treatment and sustained virologic response (SVR) 24 weeks after stopping treatment was assessed by qualitative reverse-transcription polymerase chain reaction (sensitivity 50 IU/mL).\n Overall, no significant differences could be observed in the treatment outcome between both groups. End-of-treatment and SVR rates in groups A and B were 71% vs 63% and 53% vs 54%, respectively. Patients with undetectable HCV-RNA levels already at weeks 4 and 12 had excellent SVR rates ranging from 76% to 84% regardless of treatment group, whereas patients shown to be still HCV-RNA positive at week 12 achieved significantly higher SVR rates when treated for 72 instead of 48 weeks (29% vs 17%, P = .040). A particular benefit from extended treatment duration was seen in patients with low-level viremia (<6000 IU/mL) at week 12. The frequency and intensity of adverse events was similar between the 2 groups.\n Extended treatment duration generally is not recommended in HCV type 1 infection and should be reserved only for patients with slow virologic response defined as HCV-RNA positive at week 12 but negative at week 24.", "It was hypothesized that in hepatitis C virus (HCV) genotype 1 patients, variable treatment duration individualized by first undetectable HCV RNA is as effective as standard 48-week treatment. Patients (n = 696) received peginterferon alfa-2a, 180 mg/week, or peginterferon alfa-2b, 1.5 mg/kg/week, plus ribavirin, 1000-1200 mg/day, for 48 weeks (standard, n = 237) or for 24, 48, or 72 weeks if HCV-RNA-negative at weeks 4, 8, or 12, respectively (variable, n = 459). Sustained virologic response (SVR) was achieved in 45.1% [95% confidence interval (CI) 38.8-51.4] of the patients in the standard group and in 48.8% (CI 44.2-53.3) of the patients in the variable group (P = 0.37). The percentages of patients who first achieved undetectable HCV RNA at weeks 4, 8, or 12 were 26.7%, 27.8%, and 11.3%, respectively. In the standard treatment group, 87.1%, 70.3%, and 38.1% of patients who first achieved undetectable HCV RNA at 4, 8, or 12 weeks attained SVRs, respectively. In the variable group, corresponding SVR rates were 77.2%, 71.9%, and 63.5%. Low viremia levels and young age were independent predictors of response at week 4 [rapid virologic response (RVR)]. RVR patients with baseline viremia >or=400,000 IU/mL achieved higher SVR rates when treated for 48 weeks rather than 24 weeks (86.8% versus 73.1%, P = 0.14). The only predictive factor of SVR in RVR patients was advanced fibrosis. Conclusion: Variable treatment duration ensures SVR rates similar to those of standard treatment duration, sparing unnecessary side effects and costs.", "In hepatitis C virus (HCV) genotype 1 infection, the duration of interferon-based therapy is a critical determinant in achieving sustained virologic response (SVR). Slow or late responders to peginterferon and ribavirin may benefit from an extended treatment course. We sought to determine if therapy extension could improve response rates in a United States population of slow responders. Slow response was defined by achieving at least a 2-log decrement in HCV RNA from baseline, yet having detectable HCV RNA at 12 weeks and undetectable HCV RNA at 24 weeks (polymerase chain reaction, TaqMan, Roche; detection limit 10 IU/mL). Patients were treatment-naïve, chronically infected genotype 1-infected slow responders to 1.5 mug/kg/week of peginterferon-alpha2b and 800-1400 mg/day of ribavirin and were randomly assigned 1:1 to complete a total of 48 or 72 weeks of therapy. Dose reductions and treatment discontinuations for adverse events or laboratory abnormalities were similar between the 2 treatment arms. End-of-treatment response rates were similar in the 72-week group compared with those in the 48-week group (48% versus 45%; P value not significant). Overall, the rate of SVR was superior in patients treated for 72 weeks versus 48 weeks (38% versus 18%, respectively; P = 0.026). Conclusion: Extending the treatment duration from 48 weeks to 72 weeks in genotype 1-infected patients with slow virologic response to peginterferon-alpha2b and weight-based ribavirin significantly improves SVR rates. Treatment extension does not seem to increase the rate of dose reduction or therapy discontinuation.", "The benefit of extending treatment duration with peginterferon (PEG-IFN) and ribavirin (RBV) from 48 weeks to 72 weeks for patients with chronic hepatitis C genotype 1 infection has not been well established. In this prospective, international, open-label, randomized, multicenter study, 1,428 treatment-naïve patients from 133 centers were treated with PEG-IFN alfa-2b (1.5 μg/kg/week) plus RBV (800-1,400 mg/day). Patients with detectable hepatitis C virus (HCV) RNA and a ≥2-log(10) drop in HCV RNA levels at week 12 (slow responders) were randomized 1:1 to receive 48 weeks (n = 86) or 72 weeks (n = 73) of treatment. Sustained virologic response (SVR) rates were 43% in slow responders treated for 48 weeks and 48% in slow responders treated for 72 weeks (P = 0.644). Relapse rates were similar in slow responders treated for 48 or 72 weeks (47% versus 33%, P = 0.169). The safety profile was similar in both treatment arms; serious adverse events leading to discontinuation of treatment were observed in 3.5% of slow responders treated for 48 weeks and 8.2% of those treated for 72 weeks. Among slow responders with a <2-log drop in HCV RNA at week 8, SVR was 39% in the 72-week arm and 19% in the 48-week arm.\n These data suggest that 48 weeks of therapy with PEG-IFN alfa-2b plus RBV (800-1,400 mg/day) should remain a standard-of-care treatment for treatment-naïve G1 slow responders." ]

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[ "Clinical pathway for fractured neck of femur: a prospective, controlled study.", "The critical path method in stroke rehabilitation: lessons from an experiment in cost containment and outcome improvement.", "A controlled trial of a critical pathway for treatment of community-acquired pneumonia. CAPITAL Study Investigators. Community-Acquired Pneumonia Intervention Trial Assessing Levofloxacin.", "The results of a randomized trial of a quality improvement intervention in the care of patients with heart failure. The MISCHF Study Investigators.", "Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation.", "Effectiveness of a clinical pathway for inpatient asthma management.", "An emergency department-based protocol for rapidly ruling out myocardial ischemia reduces hospital time and expense: results of a randomized study (ROMIO).", "Increasing the rate of identification of battered women in an emergency department: use of a nursing protocol.", "Collaborative care for bipolar disorder: part I. Intervention and implementation in a randomized effectiveness trial.", "Systematic detection and multidisciplinary care of delirium in older medical inpatients: a randomized trial.", "The development and establishment of a care map in children with asthma in Taiwan.", "[Electronic clinical pathway for community acquired pneumonia (e-CP CAP)].", "Effects of counseling and implementation of clinical pathway on diabetic patients hospitalized with hypoglycemia.", "Guidelines in gynaecology: evaluation in menorrhagia and in urinary incontinence.", "Protocol weaning of mechanical ventilation in medical and surgical patients by respiratory care practitioners and nurses: effect on weaning time and incidence of ventilator-associated pneumonia.", "Prospective, randomized, controlled trial between a pathway of controlled rehabilitation with early ambulation and diet and traditional postoperative care after laparotomy and intestinal resection.", "Costs of an emergency department-based accelerated diagnostic protocol vs hospitalization in patients with chest pain: a randomized controlled trial.", "Clinical pathways in hip and knee arthroplasty: a prospective randomised controlled study.", "[Clinical significance of a standardized clinical pathway in gastrectomy patients].", "Improving end-of-life care: development and pilot-test of a clinical pathway.", "Effect of a scoring system and protocol for sedation on duration of patients' need for ventilator support in a surgical intensive care unit.", "Use of an 'evidence-based implementation' strategy to implement evidence-based care of asthma into rural district hospital emergency departments.", "Integrated care pathways and quality of life on a stroke rehabilitation unit.", "Randomized controlled trial of integrated (managed) care pathway for stroke rehabilitation.", "Impact on readmission rates and mortality of a chronic obstructive pulmonary disease inpatient management guideline.", "A prospective, randomized, controlled trial of an emergency department-based atrial fibrillation treatment strategy with low-molecular-weight heparin." ]

[ "To assess outcomes of using a clinical pathway for managing patients with fractured neck of femur.\n Prospective, pseudorandomised, controlled trial.\n St Vincent's Hospital, Melbourne, Victoria (a tertiary referral, university teaching hospital), 1 October 1997 to 30 November 1998.\n 111 patients (80 women and 31 men; mean age, 81 years) admitted via the emergency department with a primary diagnosis of fractured neck of femur.\n Management guided by a clinical pathway (55 patients) or established standard of care (control group, 56 patients).\n Timing of referrals and discharge planning; total length of stay; and complication and readmission rates within 28 days of discharge.\n Patients managed according to the clinical pathway had a shorter total stay (6.6 versus 8.0 days; P = 0.03), even if assessment for placement by the Aged Care Assessment Service was required (9.5 versus 13.6 days; P = 0.03). There were no significant differences in complication and readmission rates between pathway and control patients (complication rates, 24% versus 36%; P = 0.40; readmission rates, 4% versus 11%; P = 0.28).\n Coordinated multidisciplinary care of patients with fractured neck of femur reduces length of stay without increasing complications.", "This study tested the effects of a project network technique called the Critical Path Method (CPM) on the costs and outcomes of inpatient team stroke rehabilitation. On admission to a large, academic, inpatient rehabilitation hospital adults who had a recent (< 120 days) stroke were randomly assigned to receive rehabilitation services from a team trained in CPM (N = 53) or from usual care teams (N = 68). Results showed no significant difference between groups in length of stay, hospital charges, or functional status at discharge. CPM may be effective in patient care services that are less influenced by specialization, professional issues, and external regulation and in settings where patient outcomes are relatively fixed and predictable, and medical care is integrated across institutions.", "Large variations exist among hospitals in the use of treatment resources for community-acquired pneumonia (CAP). Lack of a common approach to the diagnosis and treatment of CAP has been cited as an explanation for these variations.\n To determine if use of a critical pathway improves the efficiency of treatment for CAP without compromising the well-being of patients.\n Multicenter controlled clinical trial with cluster randomization and up to 6 weeks of follow-up.\n Nineteen teaching and community hospitals in Canada.\n A total of 1743 patients with CAP presenting to the emergency department at 1 of the participating institutions between January 1 and July 31, 1998.\n Hospitals were assigned to continue conventional management (n = 10) or implement the critical pathway (n = 9), which consisted of a clinical prediction rule to guide the admission decision, levofloxacin therapy, and practice guidelines.\n Effectiveness of the critical pathway, as measured by health-related quality of life on the Short-Form 36 Physical Component Summary (SF-36 PCS) scale at 6 weeks; and resource utilization, as measured by the number of bed days per patient managed (BDPM).\n Quality of life and the occurrence of complications, readmission, and mortality were not different for the 2 strategies; the 1-sided 95% confidence limit of the between-group difference in the SF-36 PCS change score was 2.4 points, which was within a predefined 3-point boundary for equivalence. Pathway use was associated with a 1.7-day reduction in BDPM (4.4 vs 6.1 days; P = .04) and an 18% decrease in the admission of low-risk patients (31% vs 49%; P = .01). Although inpatients at critical pathway hospitals had more severe disease, they required 1.7 fewer days of intravenous therapy (4.6 vs 6.3 days; P = .01) and were more likely to receive treatment with a single class of antibiotic (64% vs 27%; P<.001).\n In this study, implementation of a critical pathway reduced the use of institutional resources without causing adverse effects on the well-being of patients.", "Quality improvement and disease management programs for heart failure have improved quality of care and patient outcomes at large tertiary care hospitals. The purpose of this study was to measure the effects of a regional, multihospital, collaborative quality improvement intervention on care and outcomes in heart failure in community hospitals.\n This randomized controlled study included 10 acute care community hospitals in upstate New York. After a baseline period, 5 hospitals were randomly assigned to receive a multifaceted quality improvement intervention (n = 762 patients during the baseline period; n = 840 patients postintervention), while 5 were assigned to a \"usual care\" control (n = 640 patients during the baseline period; n = 664 patients postintervention). Quality of care was determined using explicit criteria by reviewing the charts of consecutive patients hospitalized with the primary diagnosis of heart failure during the baseline period and again in the postintervention period. Clinical outcomes included hospital length of stay and charges, in-hospital and 6-month mortality, hospital readmission, and quality of life measured after discharge.\n Patients had similar characteristics in the baseline and postintervention phases in the intervention and control groups. Using hospital-level analyses, the intervention had mixed effects on 5 quality-of-care markers that were not statistically significant. The mean of the average length of stay among hospitals decreased from 8.0 to 6.2 days in the intervention group, with a smaller decline in mean length of stay in the control group (7.7 to 7.0 days). The net effects of the intervention were nonsignificant changes in length of stay of -1.1 days (95% confidence interval [CI]: -2.9 to 0.7 days, P = 0.18) and in hospital charges of -$817 (95% CI: -$2560 to $926, P = 0.31). There were small and nonsignificant effects on mortality, hospital readmission, and quality of life.\n The incremental effect of regional collaboration among peer community hospitals toward the goal of quality improvement was small and limited to a slightly, but not significantly, shorter length of stay.", "To compare a practice of protocol-directed sedation during mechanical ventilation implemented by nurses with traditional non-protocol-directed sedation administration.\n Randomized, controlled clinical trial.\n Medical intensive care unit (19 beds) in an urban teaching hospital.\n Patients requiring mechanical ventilation (n = 321).\n Patients were randomly assigned to receive either protocol-directed sedation (n = 162) or non-protocol-directed sedation (n = 159).\n The median duration of mechanical ventilation was 55.9 hrs (95% confidence interval, 41.0-90.0 hrs) for patients managed with protocol-directed sedation and 117.0 hrs (95% confidence interval, 96.0-155.6 hrs) for patients receiving non-protocol-directed sedation. Kaplan-Meier analysis demonstrated that patients in the protocol-directed sedation group had statistically shorter durations of mechanical ventilation than patients in the non-protocol-directed sedation group (chi-square = 7.00, p = .008, log rank test; chi-square = 8.54, p = .004, Wilcoxon's test; chi-square = 9.18, p = .003, -2 log test). Lengths of stay in the intensive care unit (5.7+/-5.9 days vs. 7.5+/-6.5 days; p = .013) and hospital (14.0+/-17.3 days vs. 19.9+/-24.2 days; p < .001) were also significantly shorter among patients in the protocol-directed sedation group. Among the 132 patients (41.1%) receiving continuous intravenous sedation, those in the protocol-directed sedation group (n = 66) had a significantly shorter duration of continuous intravenous sedation than those in the non-protocol-directed sedation group (n = 66) (3.5+/-4.0 days vs. 5.6+/-6.4 days; p = .003). Patients in the protocol-directed sedation group also had a significantly lower tracheostomy rate compared with patients in the non-protocol-directed sedation group (10 of 162 patients [6.2%] vs. 21 of 159 patients [13.2%], p = .038).\n The use of protocol-directed sedation can reduce the duration of mechanical ventilation, the intensive care unit and hospital lengths of stay, and the need for tracheostomy among critically ill patients with acute respiratory failure.", "Clinical pathways for asthma are tools that have the potential to improve compliance with nationally recognized management guidelines, but their effect on patient outcomes has not been documented.\n To determine the effect of an asthma clinical pathway on patients' length of stay, use of nebulized beta-agonist therapy while hospitalized, and use of acute care clinics for 2 weeks after discharge.\n The study was a randomized, controlled trial. Patients between the ages of 2 and 18 years admitted with an asthma exacerbation and not under the care of an asthma specialist were eligible for the study. Patients were randomized either to a conventional ward (control group) or to a ward using the clinical pathway (intervention group). For 2 weeks after discharge, we collected data to determine whether patients visited a health care provider for worsening asthma.\n One hundred ten patients (26%) were enrolled. Control and intervention groups had similar demographic and asthma severity profiles. The intervention group had an average length of stay 13 hours shorter than did the control group. In addition, at every dosing interval, the intervention group received less nebulized beta-agonist therapy. There were no deaths in either group.\n A clinical pathway for inpatient asthma decreased the length of stay and beta-agonist medication use with no adverse outcomes or increased acute-care encounters through 2 weeks after discharge.", "We tested the hypothesis that an emergency department-based protocol for rapidly ruling out myocardial ischemia would reduce hospital time and expense but maintain diagnostic accuracy.\n Patients with a missed diagnosis of myocardial infarction have a high mortality rate; however, providing routine hospital care to low risk patients may not be time- or cost-effective.\n One hundred low risk patients were entered into the study and randomized either to an emergency department-based rapid rule-out protocol (n = 50) or to routine hospital care (n = 50). Patients receiving routine care were managed by their attending physicians. The rapid protocol included serum enzyme testing at 0, 3, 6 and 9h, serial electrocardiograms with continuous ST segment monitoring and, if results were negative, a predischarge graded exercise test. Study patients were also compared with 160 historical control subjects.\n Myocardial infarction or unstable angina occurred in 6% of patients within 30 days; no diagnoses were missed. By intention to treat analysis (n = 50 in each group), the hospital stay was shorter and charges were lower with the rapid protocol than with routine care (p = 0.001). Among patients in whom ischemia was ruled out, those assigned to the rapid protocol had a shorter hospital stay (median 11.9 vs. 22.8 h, p = 0.0001) and lower initial ($893 vs $1,349, p = 0.0001) and 30-day ($898 vs. $1,522, p = 0.0001) hospital charges than did patients given routine care. In historical control subjects, the hospital stay was longer (median 34.5 h, p = 0.001 vs. either group) and charges greater (median $2,063, p = 0.001, vs rapid protocol, p = 0.02, vs. routine care group).\n In low risk patients who present to the emergency department with chest pain, the rapid protocol ruled out myocardial infarction and unstable angina more quickly and cost-effectively than did routine hospital care.", "In recognition of the increasing problem of family violence, the authors developed and tested an interview protocol focused on female victims of family violence. The purpose of the protocol was to increase nurses' identification of battered women receiving care in the emergency department. Using a time-series design, data were collected from patient records during four months prior to introduction of the protocol. These data were compared to comparable post-protocol data. There was a significant increase in nursing staff identification of female domestic violence victims following introduction of the protocol.", "Outcome for bipolar disorder remains suboptimal despite the availability of efficacious treatments. To improve treatment effectiveness in clinical practice, a Veterans Affairs study team created a care model conceptually similar to the lithium clinics of the 1970s but augmented by principles of more recent collaborative care models for chronic medical illnesses. This intervention consists of improving patients' self-management skills through psychoeducation; supporting providers' decision making through simplified practice guidelines; and enhancing access to care, continuity of care, and information flow through the use of a nurse care coordinator. In this article, which is part I of a two-part report, the authors summarize the conceptual background and development of the intervention, describe the design of a three-year, 11-site randomized effectiveness trial, and report data describing its successful implementation. Trial design emphasized aspects of effectiveness to support generalizability of the findings and eventual dissemination of the intervention. Part II (see companion article, this issue) reports clinical, functional, and overall cost outcomes of the trial.", "Delirium is common and often goes undetected in older patients admitted to medical services. It is associated with poor outcomes. We conducted a randomized clinical trial to determine whether systematic detection and multidisciplinary care of delirium in older patients admitted to a general medical service could reduce time to improvement in cognitive status.\n Consecutive patients aged 65 or more who were newly admitted to 5 general medical units between Mar. 15, 1996, and Jan. 31, 1999, were screened with the Confusion Assessment Method within 24 hours after admission to detect prevalent delirium and rescreened within a week to detect incident cases. Patients with delirium were randomly allocated to receive the intervention or usual care. Subjects in the intervention group were seen by a geriatric specialist consultant and followed in hospital for up to 8 weeks by an intervention nurse who liaised with the consultant, attending physicians, family and the primary care nurses. Subjects in the usual care group received standard hospital services but could consult geriatric specialists as needed. A research assistant, blinded as to treatment allocation, administered within 24 hours after enrolment the MiniMental Status Exam (MMSE), Delirium Index (measuring the severity of the delirium) and Barthel Index (measuring independence of personal care). Improvement was defined as an increase in the MMSE score of 2 or more points, with no decrease below baseline plus 2 points, or no decrease below a baseline MMSE score of 27. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly was completed to identify patients with possible dementia. Subjects were assessed 3 times during the first week and weekly thereafter for up to 8 weeks in hospital or until discharge. Data on clinical severity of illness, length of stay and living arrangements after discharge were also collected. The primary outcome measure was time to improvement in MMSE score.\n Of the 1925 patients who met the inclusion criteria and were screened, 227 had prevalent or incident delirium and consented to participate (113 in intervention group and 114 in usual care group). There were no clinically significant differences between the intervention and usual care groups except for sex (female 58.4% v. 50.0%) and marital status (married 34.8% v. 41.2%). Overall, 48% of the patients in the intervention group and 45% of those in the usual care group met the predetermined criteria for improvement. The Cox proportional hazards ratio (HR) for a shorter time to improvement with the intervention versus usual care, adjusted for age, sex and marital status, was 1.10 (95% confidence interval [CI] 0.74-1.63). There were no significant differences within 8 weeks after enrolment between the 2 groups in time to and rate of improvement of the Delirium Index, the Barthel Index, length of stay, rate of discharge to the community, living arrangements after discharge or survival. Outcomes between the 2 groups did not differ statistically significantly for patients without dementia (HR 1.54, 95% CI 0.80-2.97), for those who had less co-morbidity (HR 1.36, 95% CI 0.75-2.46) or for those with prevalent delirium (HR 1.15, 95% CI 0.48-2.79).\n Systematic detection and multidisciplinary care of delirium does not appear to be more beneficial than usual care for older patients admitted to medical services.", "It is often difficult to predict the timing and frequency of asthma attacks. In addition to interrupting the daily life of both the affected child and his/her family, asthma can also pose sudden danger to a child. Based on clinical observations, many asthma-affected children and their parents must constantly adjust themselves to the uncertainty of the disease, which leads to increased stress on the family. The use of care maps has demonstrated increased efficiency and effectiveness in the care of asthma patients from a variety of settings.\n We designed this study to construct and evaluate a care map for asthmatic children in Taiwan. Specific attention was placed on comparing the study and control subjects by parental knowledge of asthma, medication used for asthma, hospital readmission, and health care resource usage.\n The care map was constructed by in-depth interviews with eight sets of parents of children with asthma. Forty-four parents of 42 asthma children were randomized into two groups in the Allergic Clinic of the Chang Gung Children's Hospital. The experimental group of 22 parents received individual instruction and training sessions in addition to the regular care provided to the control group of 22 parents.\n Forty-two children with asthma were surveyed in this study. To examine the reliability and validity of a care map for children with asthma, a quantitative survey was conducted with 42 outpatient parents with asthmatic children. There was less emergency room attending rate in experimental group (6/month; p<0.05) The understanding of the disease was much improved in parents of experimental group (13.85+/-1.04 vs. 10.91+/-2.14; p<0.01). Furthermore, parents acquired a more positive attitude to asthma, and almost all of the control group had irregular follow-ups by a physician and had irregular use of medication.\n This study emphasizes that a care map in children with asthma (CACM) can be used to educate parents in how to provide the best treatment plan for their children. This study also shows how a CACM can help parents train their children in the best behaviors during asthma attacks. Empathetic assessment and elimination of cultural barriers, a well-designed educational program, and a mutually developed treatment plan could significantly improve the quality of life for families and specific asthma outcomes.", "Clinical pathway is a useful strategy for the management of risk and cost for medical care. We developed an electronic clinical pathway (e-CP) for community acquired pneumonia (CAP). We programmed all medical procedures, including physical and laboratory examinations, medical care, prescriptions, diets, limitations of activities, and patient education on a computer. With e-CP, we achieved 30% cost reduction (34048 points vs. 24338 points), 25% shortening of admission duration (10.77 days vs. 8.03 days) and 21% shortening of the duration of intravenous antibiotics administration (8.22 days vs. 6.47 days). Introduction of computer-aided clinical pathway for CAP may contribute to the standardization of medical care for patients with CAP.", "A prospective randomized controlled study was conducted to examine the effects of counseling and implementation of clinical pathway on type 2 diabetic patients hospitalized with hypoglycemia.\n Thirty- three cases received counseling and clinical pathway for treatment of hypoglycemia (study group) and another 32 cases received conventional treatment for hypoglycemia (control group) in Taksin Hospital between July and December 2005.\n Both groups have similar age, sex, and mean serum glucose on admission. There were also no differences between the two groups in terms of number of patients with chronic diabetic complications, acute concurrent illness and pattern of hypoglycemic drugs used for treatment. Average length of hospital stay of the study group was significantly lower than that of the control group (3.94 +/- 1.03 vs 6.38 +/- 4.05; p = 0.0005). There were also a significant decrease in the mean number of capillary blood glucose tests performed in the study group compared to the control group (10.03 +/- 5.04 vs 12.34 +/- 5.96; p = 0.048). Subsequent readmissions with recurrent hypoglycemia at 1 and 3 months interval after being discharged from the hospital decreased significantly in the study group (6.06 % vs 34.38 %; p = 0.036). While there was considerable reduction in mean medical cost in the study group, it did not reached a statistically significant difference when compared with the control group (2,743.58 +/- 1,473.04 vs 3,687 +/- 3,110.82; p = 0.06).\n Counseling and implementation of clinical pathway on type 2 diabetic patients hospitalized with hypoglycemia can reduce the length of hospital stay and decrease readmission rates of recurrent hypoglycemia. This results in considerable health and economic benefits.", "To evaluate the effectiveness of national guidelines and local protocols in improving hospital care (process and outcome) for women with menorrhagia and for women with urinary incontinence.\n 2 x 2 balanced incomplete block controlled before and after study.\n Gynaecology units in four district general hospitals across Scotland.\n National guidelines were adapted locally to protocols, which were disseminated at specific local educational meetings and implemented by placing a copy of the appropriate protocol in women's hospital casenotes prior to consultation.\n Four hundred and ninety-seven women with menorrhagia and 449 women with urinary Incontinence.\n Process of care within six key areas of clinical practice: initial hospital assessment; appropriate use of hospital investigations; inappropriate use of hospital investigations; appropriate first line treatments; appropriate pre-surgery assessment; and use of surgical treatments. Outcome of care using condition-specific outcome measures and four domains of SF-36 at zero, six and twelve months following intervention.\n There were significant improvements with the introduction of guidelines and protocols in two (initial hospital assessment and appropriate pre-surgery assessment) of the six key areas of clinical practice assessed. In the other areas there were no significant improvements or deteriorations observed. There was no evidence of effect of guidelines and protocols on the condition-specific outcome measures or on the four domains of the SF-36.\n There were only very modest benefits observed from the introduction of guidelines and protocols on the hospital management of the two conditions. The reasons for this lack of impact of the guidelines is unclear. Experience of this study raises important methodological issues for future research in this area.", "(1) To determine the effect of a single ventilator management protocol (VMP) used in medical and surgical ICUs on the duration of mechanical ventilation. (2) To determine the effect of a VMP on the incidence of ventilator-associated pneumonia (VAP).\n Prospective, randomized, controlled study.\n : University medical center.\n Three hundred eighty-five patients receiving mechanical ventilation between June 1997 and May 1998.\n A respiratory care practitioner- and registered nurse-driven VMP.\n Intervention and control groups were comparable with respect to age, sex, severity of illness and injury, and duration of respiratory failure at the time of randomization. The duration of mechanical ventilation for patients was decreased from a median of 124 h for the control group to 68 h in the VMP group (p = 0.0001). Thirty-one total instances of VAP were noted. Twelve patients in the surgical control group had VAP, compared with 5 in the surgical VMP group (p = 0.061). The impact of the VMP on VAP frequency was less for medical patients. Mortality and ventilator discontinuation failure rates were similar between control and VMP groups.\n A VMP designed for multidisciplinary use was effective in reducing duration of mechanical ventilatory support without any adverse effects on patient outcome. The VMP was also associated with a decrease in incidence of VAP in trauma patients. These results, in conjunction with prior studies, suggest that VMPs are highly effective means of improving care, even in university ICUs.", "In an era of dwindling hospital resources and increasing medical costs, safe reduction in postoperative stay has become a major focus to optimize utilization of healthcare resources. Although several protocols have been reported to reduce postoperative stay, no Level I evidence exists for their use in routine clinical practice.\n Sixty-four patients undergoing laparotomy and intestinal or rectal resection were randomly assigned to a pathway of controlled rehabilitation with early ambulation and diet or to traditional postoperative care. Time to discharge from hospital, complication and readmission rates, pain level, quality of life, and patient satisfaction scores were determined at the time of discharge and at 10 and 30 days after surgery. Subgroups were defined to evaluate those who derived the optimal benefit from the protocol.\n Pathway patients spent less total time in the hospital after surgery (5.4 vs. 7.1 days; P = 0.02) and less time in the hospital during the primary admission than traditional patients. Patients younger than 70 years old had greater benefits than the overall study group (5 vs. 7.1 days; P = 0.01). Patients treated by surgeons with the most experience with the pathway spent significantly less time in the hospital than did those whose surgeons were less experienced with the pathway (P = 0.01). There was no difference between pathway and traditional patients for readmission or complication rates, pain score, quality of life after surgery, or overall satisfaction with the hospital stay.\n Patients scheduled for a laparotomy and major intestinal or rectal resection are suitable for management by a pathway of controlled rehabilitation with early ambulation and diet. Pathway patients have a shorter hospital stay, with no adverse effect on patient satisfaction, pain scores, or complication rates. Patients younger than 70 years of age derive the optimal benefit, and increased surgeon experience improves outcome.", "More than 3 million patients are hospitalized yearly in the United States for chest pain. The cost is over $3 billion just for those found to be free of acute disease. New rapid diagnostic tests for acute myocardial infarction (AMI) have resulted in the proliferation of accelerated diagnostic protocols (ADPs) and chest pain observation units.\n To determine whether use of an emergency department (ED)-based ADP can reduce hospital admission rate, total cost, and length of stay (LOS) for patients needing admission for evaluation of chest pain.\n Prospective randomized controlled trial comparing admission rate, total cost, and LOS for patients treated using ADP vs inpatient controls. Total costs were determined using empirically measured resource utilization and microcosting techniques.\n A large urban public teaching hospital serving a predominantly African American and Hispanic population.\n A sample of 165 patients was randomly selected from a larger consecutive sample of 429 patients with chest pain concurrently enrolled in an ADP diagnostic cohort trial. Eligible patients presented to the ED with clinical findings suggestive of AMI or acute cardiac ischemia (ACI) but at low risk using a validated predictive algorithm.\n Primary outcomes measured for each subject were LOS and total cost of treatment.\n The hospital admission rate for ADP vs control patients was 45.2% vs 100% (P<.001). The mean total cost per patient for ADP vs control patients was $1528 vs $2095 (P<.001). The mean LOS measured in hours for ADP vs control patients was 33.1 hours vs 44.8 hours (P<.01).\n In this trial, ADP saved $567 in total hospital costs per patient treated. Use of ED-based ADPs can reduce hospitalization rates, LOS, and total cost for low-risk patients with chest pain needing evaluation for possible AMI or ACI.", "To ascertain the effectiveness of clinical pathways for improving patient outcomes and decreasing lengths of stay after hip and knee arthroplasty.\n Twelve-month randomised prospective trial comparing patients treated through a clinical pathway with those treated by an established standard of care at a single tertiary referral university hospital.\n 163 patients (56 men and 107 women; mean age, 66 years) undergoing primary hip or knee arthroplasty, and randomly allocated to the clinical pathway (92 patients) and the control group (71 patients).\n Time to sitting out of bed and walking; rates of complications and readmissions; match to planned discharge destination; and length of hospital stay.\n Clinical pathway patients had a shorter mean length of stay (P = 0.011), earlier ambulation (P = 0.001), a lower readmission rate (P = 0.06) and closer matching of discharge destination. There were beneficial effects of attending patient seminars and preadmission clinics for both pathway and control patients.\n Clinical pathway is an effective method of improving patient outcomes and decreasing length of stay following hip and knee arthroplasty.", "In traditional practice patterns, physicians take care of all clinical decisions, such as diagnosis, treatment, and recovery. In the Nippon Medical School Hospital a clinical pathway for distal gastrectomy patients, recorded as a post-operative care map, was introduced in August 2000. In January 2001 the post-operative management was analyzed and standardization of practice was carried out with printed order sets, such as drugs and infusion solutions. The aim of this study was to evaluate the clinical significance of the clinical pathway for gastrectomy patients by employing standardized postoperative management and printed order sets.\n From January 2001 to December 2001, 87 patients underwent distal (43), total (28), proximal (7) and partial gastrectomy (9) for gastric cancer (stage IA: 47, IB: 9, II: 7, IIIA: 8, IIIB 2, IV: 10) and gastrointestinal stromal tumor (4). These patients were randomly assigned to either the main building or the east building of our hospital. In the main building 38 patients were looked after using traditional practice (control group). In the east building 47 patients were looked after according to the clinical pathway (path group) and 2 patients were excluded from the path group because of neo-adjuvant chemotherapy and severe heart failure. Aspects of the patients' outcomes, including length of stay, the first day of the diet, morbidity, and medical costs, were compared between the path group and the control group. All data were expressed as means+/-standard deviation. Statistical analyses were made using Student t-test, Mann-Whitney U-test, and chi(2) test, and the 5%level was chosen for statistical significance.\n The length of the hospital stay was 27.1+/-10.0 and 40.8+/-26.1 days (p<0.005) and the length of post-operative stay was 18.1+/-9.5 and 28.2+/-22.3 days (p<0.01) in the path group and the control group, respectively. The post-operative day when the diet was started for the path and control groups was 6.8+/-8.9 and 8.2+/-7.2, respectively; however, the length of the intravenous infusion for the two groups was 11.8+/-1.1 and 16.5+/-1.2 days (p<0.01), respectively. There was no statistically significant difference in the morbidity rate between the path group (3/47) and the control group (5/38). The total cost was 1,502,587 yen +/-41,650 in the path group and 1,932,197 yen +/-131,030 in the control (p<0.001).\n A clinical pathway for gastrectomy patients proved useful to optimize their postoperative care, including medication management and diet education. It is suggested that the implementation of a standardized clinical pathway for gastrectomy patients reduced the length of the hospital stay and the medical costs.", "Prior studies have revealed deficiencies in the care provided to patients dying from advanced medical illnesses in acute care hospitals. These deficiencies are best addressed through system change, which may include the development of clinical pathways and quality improvement models. The Palliative Care for Advanced Disease (PCAD) pathway was developed by an interdisciplinary team and includes a carepath, a daily flowsheet, and a physician order sheet with standard orders for symptom control. To evaluate the utility of PCAD, the clinical pathway was introduced on three hospital units (Oncology, Geriatrics, and an inpatient palliative care/hospice unit) as part of a quality improvement initiative and outcomes were compared to two general medical units receiving usual care. A chart audit tool (CAT) was used to review medical records of 101 patients who died on one of these five units during the year prior to implementation (baseline) and 156 who died during the nine months of the PCAD intervention. Four indices from CAT evaluated change over time: the mean number of 1) symptoms assessed, 2) problematic symptoms, 3) interventions consistent with PCAD, and 4) consultations requested. Nine of 27 (33%) patients on the Oncology/Geriatrics units and all 50 patients who died on the palliative care/hospice unit were placed on PCAD. During the PCAD intervention, dying patients who resided on Geriatrics, Oncology and palliative care/hospice units were more likely to have DNR orders than the comparison units, whereas the comparison units were more likely to use \"morphine infusions\" and cardiopulmonary resuscitation than the units that received the PCAD intervention. The mean number of symptoms assessed increased significantly in all units (P < 0.001 for all comparisons). The number of problematic symptoms identified (P=0.014) and the number of interventions consistent with PCAD increased only on the palliative care/hospice unit (P=0.021). The number of medical consultations declined on all units and reached significance on the Geriatrics and Oncology units (P=0.037). Although these results reflect less than one year of the PCAD intervention and must be considered preliminary, they suggest that 1) a clinical pathway such as PCAD can serve as a managerial and educational tool to improve the care of the imminently dying inpatient; 2) a PCAD clinical pathway can be implemented on hospital units as a quality improvement initiative--a \"PCAD intervention;\" 3) a PCAD intervention can change outcomes in a positive direction, as measured using a chart audit tool; 4) a PCAD intervention can promote aggressive symptom assessment and treatment when goals of care are aimed at comfort; and 5) changes may occur in units that do not directly receive the intervention, a phenomenon that suggests the possibility of diffusion. Further study of this systems-oriented approach to change is warranted and should include direct assessment of patient and family outcomes, as well as measures of process.", "Need for improved sedation strategy for adults receiving ventilator support.\n Observational study of effect of introduction of guidelines to improve the doctors' and nurses' performance. The project was a prospective improvement and was part of a national quality improvement collaborative.\n A general mixed surgical intensive care unit in a university hospital; all doctors and nurses in the unit; all adult patients (>18 years) treated by intermittent positive pressure ventilation for more than 24 hours.\n Reduction in patients' mean time on a ventilator and length of stay in intensive care over a period of 11 months; anonymous reporting of critical incidents; staff perceptions of ease and of consequences of changes.\n Multiple measures (protocol development, educational presentations, written guidelines, posters, flyers, emails, personal discussions, and continuous feedback) were tested, rapidly assessed, and adopted if beneficial. Effects of change: Mean ventilator time decreased by 2.1 days (95% confidence interval 0.7 to 3.6 days) from 7.4 days before intervention to 5.3 days after. Mean stay decreased by 1.0 day (-0.9 to 2.9 days) from 9.3 days to 8.3 days. No accidental extubations or other incidents were identified.\n Relatively simple changes in sedation practice had significant effects on length of ventilator support. The change process was well received by the staff and increased their interest in identifying other areas for improvement.", "To determine if an evidence-based implementation (EBI) could lead to the successful implementation of evidence based care for adult asthma in small rural district hospitals.\n A controlled trial involving eight small rural hospitals (four each in the study and control groups) was conducted. Retrospective pre-intervention audits were conducted at all eight hospitals for 7 months (1 January 2004 to 31 July 2004) and evidence-practice gaps identified. An EBI was then used to implement established guidelines for the management of asthma in the study hospitals. Post-intervention audits were then performed over a period of 7 months (1 October 2004 to 31 April 2005).\n There were 52 presentations of asthma in the study hospitals in the pre-implementation phase and 47 post-implementation. The corresponding numbers for the control hospitals were 46 and 42 respectively. There were no statistically significant differences in the severity between the groups. Following the EBI there were significant improvements at the study hospitals for the documentation of severity (8% to 62%, p <0.001), use of spirometry (12% to 62%, p <0.001) and the use of written short-term asthma plans (9% to 26%, p = 0.05). There was a decrease in use of ipratropium in mild asthma (44% to 30%, p = 0.228), an increase in the use of systemic steroids (61% to 72%, p = 0.255) and no change in prescribing antibiotics for afebrile patients with asthma (21% to 21% p = 0.956). There was no significant change in practice at the control hospitals except for a decrease in the use of systemic steroids (48% to 21%, p = 0.011). For the six clinical indicators aggregate there was a significant increase in compliance with guidelines at the study hospitals (36% to 62%, p < 0.001) but no change at the control hospitals (31% to 31%, p = 0.970).\n The pre-intervention audits demonstrated low levels of compliance with asthma guidelines across six clinical indicators. An EBI significantly improved compliance across these six indicators, and no improvement was noted in the control hospitals. This study demonstrates that an EBI can alter clinical practice in small rural district hospitals.", "Integrated care pathways (ICP) may not reduce disability, institutionalization, or duration of hospitalization compared with conventional multidisciplinary team (MDT) care in organized stroke rehabilitation. Their potential to improve patient heath status or satisfaction with care is not known.\n A comparison of quality of life, caregiver strain, and patient/caregiver satisfaction at 6 months after stroke was undertaken in 152 stroke patients randomized to receive ICP or MDT care. Differences in processes of care were recorded with the use of a predefined schedule. Multivariate analyses were undertaken to identify the effect of age, sex, stroke severity, functional status, mood, and use of care pathway on quality of life score.\n The 2 groups were comparable for baseline characteristics of age, sex, stroke severity, and initial disability. MDT care was characterized by greater emphasis on return of higher function and caregiver needs compared with ICP. EuroQol Visual Analogue Scale (EQ-VAS) scores were higher in the MDT group (median, 72 versus 63; P<0.005), who also had higher scores for EuroQol dimension of social functioning (P=0.014). Higher EQ-VAS scores were independently related to MDT care (P=0.04), Rankin score (P=0.01), and psychological function (P<0.0001) but not to age, sex, or stroke severity. There were no significant differences in patient or caregiver satisfaction between the 2 settings.\n Better quality of life in patients receiving conventional MDT care may be attributable to improved social functioning and greater attention to higher function and caregiver needs during rehabilitation.", "Integrated Care Pathway (ICP) is an organized, goal-defined, and time-managed plan that has the potential of facilitating timely interdisciplinary coordination, improving discharge planning, and reducing length of hospital stay.\n An ICP for stroke rehabilitation based on evidence of best practice, professional standards, and existing infrastructure was developed. Its effectiveness was tested in 152 stroke patients undergoing rehabilitation who were randomized to receive ICP care coordinated by an experienced nurse (n=76) or conventional multidisciplinary care (n=76).\n The age, sex, premorbid functional ability, and stroke characteristics of the 2 groups were comparable. There were no differences in mortality rates (10 [13%] versus 6 [8%]), institutionalization (10 [13%] versus 16 [21%]), or length of hospital stay (50+/-19 versus 45+/-23 days) between patients receiving ICP or multidisciplinary care. Patients receiving conventional multidisciplinary care improved significantly faster between 4 and 12 weeks (median change in Barthel Activities of Daily Living Index 6 versus 2; P<0.01) and had higher Quality of Life scores at 12 weeks (65 versus 59; P=0.07) and 6 months (72 versus 63; P<0.005). There were no significant differences in the mean duration of physiotherapy (42.8+/-41.2 versus 39.4+/-36.4 hours) or occupational therapy (8.5+/-7.5 versus 8.0+/-7.5 hours) received between the 2 groups.\n ICP management offered no benefit over conventional multidisciplinary care on a stroke rehabilitation unit. Functional recovery was faster and Quality of Life outcomes better in patients receiving conventional multidisciplinary care.", "Chronic obstructive pulmonary disease (COPD) is a common condition associated with considerable morbidity, mortality and hospital admissions. However, published COPD management guidelines have major limitations and lack practical summaries. We aimed to optimally develop, implement, and evaluate a multidisciplinary COPD inpatient management 'ACCORD' guideline, including prompts for comprehensive day one assessments through to a discharge criteria checklist.\n Two intervention and two control public teaching hospitals in Adelaide, South Australia, took part, with pre-intervention (721 COPD admissions over 7 months) and intervention phases (509 COPD admissions over 7 months). During the intervention stage the ACCORD guideline was placed in the case notes on the day of admission or soon after. Readmissions were categorized as either emergency or elective and compared between the study arms, as were mortality and potential confounders (age, gender, number of comorbidities), with Poisson regression analysis.\n Of case notes of eligible COPD patients, 60% had the ACCORD guideline placed, of which 76% had evidence of use as judged by completion of guideline entry and tick boxes. The ACCORD guideline was associated with an increase in elective admissions and a reduction in emergency admissions in the intervention group in relation to the control group (P < 0.01), with no difference in overall admissions or death rates.\n The ACCORD guideline was associated with a shift from emergency admissions to more planned elective care, suggesting more proactive care of health problems, but without overall reduction in admissions.", "We assess an alternative accelerated clinical pathway approach to the management of patients with newly diagnosed or new-onset atrial fibrillation (AF).\n A prospective, randomized pilot study of 2 AF disease-management strategies was conducted at a single university hospital. A traditional approach of hospital admission versus an accelerated emergency department-based strategy with low-molecular-weight heparin and early cardioversion to sinus rhythm was assessed in a cohort of patients with uncomplicated AF. The primary end points were length of stay and total actual direct costs.\n Eighteen patients were randomized over a 15-month period. The accelerated treatment strategy in the ED resulted in a substantial decrease in length of stay (2.1+/-2.3 versus <1 day) and a favorable trend toward mean cost reduction ($1,706+/-$1,512 versus $879+/-$394; P =.15). The clinical outcomes (rate of sinus rhythm at discharge and follow-up and complications caused by AF) related to AF were similar in the 2 groups.\n A disease-management strategy for new, uncomplicated AF that uses an ED-outpatient treatment pathway results in a shorter length of stay at potentially lower cost. The results of this pilot study warrant further investigation." ]

[ "1691921", "10880550", "1650266", "9849452", "15454647", "1649267", "10506617", "10945489", "1849786", "2465815", "2833577", "8387607" ]

[ "A randomised trial of cisplatin and vindesine versus supportive care only in advanced non-small cell lung cancer.", "Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer.", "[Is chemotherapy with cisplatin useful in non small cell bronchial cancer at staging IV? Results of a randomized study].", "Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group.", "Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life.", "A randomized trial of alternating chemotherapy versus best supportive care in advanced non-small-cell lung cancer.", "Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life.", "Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer--a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer.", "Symptomatic treatment versus combination chemotherapy for patients with extensive non-small cell lung cancer.", "Supportive care versus supportive care and combination chemotherapy in metastatic non-small cell lung cancer. Does chemotherapy make a difference?", "Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial.", "Cisplatin-cyclophosphamide-mitomycin combination chemotherapy with supportive care versus supportive care alone for treatment of metastatic non-small-cell lung cancer." ]

[ "The value of chemotherapy in advanced non-small cell lung cancer (NSCLC) remains contentious. Because of this two separate but very similar trials were set up in Australia and Southampton (UK). Two hundred and one patients with stage IIIb or IV NSCLC were randomly assigned to cisplatin 120 mg m-2 on days 1 and 29 and vindesine 3 mg m-2 weekly x 6 or to no chemotherapy. Both groups were eligible to receive radiotherapy or other palliative treatment as required. Of 188 evaluable patients, 97 received chemotherapy and 91 were in the control arm. Response was assessed between days 42 and 49. Responders continued chemotherapy at the same doses though cisplatin being given 6 weekly x 4 and the vindesine 2 weekly x 12. The overall response rate to chemotherapy was 28%; there were no significant differences according to major prognostic criteria. Although the overall survival of the chemotherapy group (median 27 weeks) was longer than that of the no chemotherapy group (median 17 weeks) this was not statistically significant (log rank P = 0.33). For patients without dissemination (IIIb), median survival was 45 weeks in the chemotherapy arm and 26 weeks in the non-chemotherapy (log rank P = 0.075). Toxicity was universal and frequently severe: of 17 patients discontinuing chemotherapy after one cycle, 13 did so because of unacceptable toxicity. This chemotherapy cannot be recommended as routine treatment. Further phase III studies of chemotherapy in advanced NSCLC should continue to use a no chemotherapy control and should also attempt to measure quality of life, an issue not addressed effectively in this or other recent trials.", "In phase II trials, paclitaxel has been shown to have antitumor activity in patients with advanced non-small-cell lung cancer (NSCLC). However, the survival and quality-of-life (QOL) benefits of paclitaxel used as a single agent compared with supportive care alone have not been assessed in a randomized clinical trial.\n A total of 157 patients with stage IIIB or IV NSCLC who had received no prior chemotherapy were randomly assigned to receive either best supportive care alone (78 patients) or paclitaxel plus supportive care (79 patients). Paclitaxel was administered as a 3-hour intravenous infusion every 3 weeks. Supportive care included palliative radiotherapy and supportive therapy with corticosteroids, antibiotics, analgesics, antiemetics, transfusions, and other symptomatic therapy as required. The primary end point of the study was survival. Time to disease progression, response rate, adverse events, and QOL were secondary end points.\n Pretreatment characteristics were evenly distributed between the two arms. Survival was statistically significantly better in the paclitaxel plus supportive care arm than in the supportive care alone arm (two-sided P =.037) (median survival = 6.8 months versus 4.8 months). Cox multivariate analysis showed paclitaxel plus supportive care to be statistically significantly associated with improved survival (two-sided P =.048). QOL was similar for both treatment arms, except for the functional activity score of the Rotterdam Symptom Checklist, where QOL data statistically significantly favored the paclitaxel plus supportive care arm (two-sided P =.043).\n The addition of paclitaxel to best supportive care significantly improved survival and time to disease progression compared with best supportive care in patients with advanced NSCLC and may improve some aspects of QOL.", "The benefit of chemotherapy for patients with disseminated non small cell lung cancer (NSCLC) is controversial. The introduction of cisplatinum in the combination chemotherapy for NSCLC gave rise to higher response rates. To study the question of the usefulness of cisplatinum-based chemotherapy in disseminated NSCLC we conducted a prospective randomized trial comparing best supportive care to vindesine + cisplatin. Between December 1985 and March 1988, 49 patients with stage IV NSCLC were enrolled. Of the 46 eligible patients 24 were in the chemotherapy group and 22 in the best supportive care group. The treatment groups were not significantly different in terms of age, performance status, histology. Toxicity on the chemotherapy arm grade 3 or more was observed in 17.5% for neutropenia, in 8.75% for vomiting. There was one death related to treatment. The overall response rate in the chemotherapy group was 41.7%. Patients of the chemotherapy group had a median survival time of 199 days and the patients of the best supportive care group had a median survival time of 73 days. The difference in survival is highly significant (p less than 0.001).", "The aim of the present trial was to evaluate the effects of chemotherapy on the quality of life and survival of patients with advanced non-small cell lung cancer (NSCLC) (stage IIIB or IV). In a controlled multicentre trial, patients were randomised to receive supportive care only or supportive care plus chemotherapy. Chemotherapy consisted of intravenous (i.v.) carboplatin 300 mg/m2 on day 1 and etoposide 120 mg/m2 orally on days 1-5 every 4 weeks for a maximum of eight courses. Quality of life was measured at randomisation and prior to each treatment course and at corresponding 4-week intervals in the control arm, using the EORTC QLQ-C30 + LC13 questionnaire. 48 patients were randomised (supportive care 26, chemotherapy 22), being eligible for comparative analyses. Another 102 patients, 97 of which received chemotherapy, were subsequently included in the study on an individual treatment preference basis. Data from these patients were used for confirmative purposes. Patients in the chemotherapy group reported better overall physical functioning and symptom control compared with the supportive care group. Group differences were smaller within the psychosocial domain, although trends were seen in favour of the chemotherapy group. No significant differences were seen in favour of the supportive care group, except for hair loss. Median survival times were 29 weeks in the chemotherapy group versus 11 weeks in the supportive care group, and 1-year survival rates were 28% versus 8%. Quality of life and survival outcomes were similar in the randomised and non-randomised patients receiving chemotherapy. No treatment-related deaths occurred. In conclusion, treatment with carboplatin and etoposide can improve both the quality of life and the survival of patients with advanced NSCLC.", "In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings. However, the meta-analysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens.\n The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364).\n 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less from chemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival.\n The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enable patients and their clinicians to make more informed treatment choices.", "From April 1985 to September 1988, 128 patients with advanced non-small-cell lung cancer (NSCLC) were enrolled in a prospective randomized trial evaluating chemotherapy (arm A) versus best supportive care (arm B). Chemotherapy consisted of cyclophosphamide 500 mg/m2 intravenously (IV) day 1, epirubicin 50 mg/m2 IV day 1, and cisplatin 80 mg/m2 IV day 1 (CE'P regimen) alternating every 4 weeks with methotrexate 30 mg/m2 IV day 1, etoposide 200 mg/m2 IV day 1, and lomustine (CCNU) 70 mg/m2 orally day 1 (MEC' regimen) until progression. Of the 123 patients (62 treated and 61 controls) eligible for survival, 115 were fully evaluable for response (58 treated and 57 controls). Response rates were 21% partial response, 53% stable disease, and 26% progressive disease in arm A, and 47% stable disease and 53% progressive disease in arm B. Median survival was 34.3 weeks (range, 4.3 to 218.6+ weeks) in arm A versus 21.1 weeks (range, 4.3 to 188.6 weeks) in arm B; the difference was not significant at P = .153 (Mantel-Cox). Subgroups of patients retrospectively analyzed by age, performance status, stage M0/M1, and weight loss or not showed no significant difference in survival. Poor-risk patients (at least two of the following: poor performance status, stage M1, weight loss) of arm A survived significantly longer than poor-risk patients of arm B (23.6 weeks v 12.4 weeks, Mantel-Cox P = .008); a significant difference in survival was also observed between nonsquamous cell patients of arm A and those of arm B (median survival, 38.6 weeks v 16.7 weeks; Mantel-Cox P = .041). Toxicity on the chemotherapy arm was hematologic (World Health Organization [WHO] grade greater than 3) in 12% of CE'P and in 13% of MEC' courses and gastroenteric (WHO grade greater than 3) in 24% of CE'P courses and in 8% of MEC' courses. Our alternating treatment was not significantly superior to supportive care. It is likely that certain subgroups of the NSCLC category may have an advantage with chemotherapy.", "Chemotherapy for non-small-cell lung cancer (NSCLC) remains controversial. We describe the two largest reported, randomized, parallel trials designed to determine whether the addition of chemotherapy influences duration and quality of life in localized, unresectable (mitomycin, ifosfamide, cisplatin [MIC]1 trial) and extensive (MIC2 trial) disease.\n Ambulatory patients with NSCLC, aged 75 years or younger, with localized disease, were randomized in MIC1 to receive up to four cycles of chemotherapy (CT: mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) every 21 days, followed by radical radiotherapy (CT + RT) or radiotherapy (RT) alone. Extensive-stage patients were randomized in MIC2 to identical chemotherapy plus palliative care (CT + PC) or palliative care (PC) alone. Short-term change in quality of life (QOL) was assessed in a subgroup of patients. Data from the two trials were combined to allow multivariate and stratified survival analyses.\n Seven hundred ninety-seven eligible patients were randomized, 446 in MIC1 and 351 in MIC2. MIC CT improved survival in both trials (significantly in MIC2). The median survival time in MIC1 was 11.7 months (CT + RT) versus 9.7 months (RT alone) (P =.14); whereas in MIC2, median survival time was 6.7 months (CT + PC) compared with 4. 8 months (PC alone) (P =.03). QOL, assessed in 134 patients from start of trial to week 6, showed improvement with chemotherapy and deterioration with standard treatment. In the combined analysis of 797 randomized patients, the positive effect of MIC on survival was significant overall (P =.01) and after adjusting for prognostic factors (P =.01).\n MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL.", "Three hundred patients with symptomatic, locally advanced or metastatic NSCLC not requiring immediate radiotherapy were enrolled into this randomized multicentre trial comparing gemcitabine + BSC vs BSC alone. Patients allocated gemcitabine received 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle, for a maximum of six cycles. The main aim of this trial was to compare patient assessment of a predefined subset of commonly reported symptoms (SS14) from the EORTC QLQ-C30 and LC13 scales. The primary end-points were defined as (1) the percentage change in mean SS14 score between baseline and 2 months and (2) the proportion of patients with a marked (> or = 25%) improvement in SS14 score between baseline and 2 months sustained for > or =4 weeks. The secondary objectives were to compare treatments with respect to overall survival, and multidimensional QL parameters. The treatment groups were balanced with regard to age, gender, Karnofsky performance status (KPS) and disease stage (40% had metastatic disease). The percentage change in mean SS14 score from baseline to 2 months was a 10% decrease (i.e. improvement) for gemcitabine plus BSC and a 1% increase (i.e. deterioration) for BSC alone (P = 0.113, two-sample t-test). A sustained (> or = 4 weeks) improvement (> or =25%) on SS14 was recorded in a significantly higher proportion of gemcitabine + BSC patients (22%) than in BSC alone patients (9%) (P = 0.0014, Pearson's chi-squared test). The QLQ-C30 and L13 subscales showed greater improvement in the gemcitabine plus BSC arm (in 11 domains) than in the BSC arm (one symptom item). There was greater deterioration in the BSC alone arm (six domains/items) than in the gemcitabine + BSC arm (three QL domains). Tumour response occurred in 19% (95% CI 13-27) of gemcitabine patients. There was no difference in overall survival: median 5.7 months (95% CI 4.6-7.6) for gemcitabine + BSC patients and 5.9 months (95% CI 5.0-7.9) (log-rank, P = 0.84) for BSC patients, and 1 -year survival was 25% for gemcitabine + BSC and 22% for BSC. Overall, 74 (49%) gemcitabine + BSC patients and 119 (79%) BSC patients received palliative radiotherapy. The median time to radiotherapy was 29 weeks for gemcitabine + BSC patients and 3.8 weeks for BSC. Patients treated with gemcitabine + BSC reported better QL and reduced disease-related symptoms compared with those receiving BSC alone. These improvements in patient-assessed QL were significant in magnitude and were sustained.", "In a randomized clinical trial, 87 patients with inoperable, extensive non-small cell lung cancer (NSCLC) were randomized to receive either combination chemotherapy (cisplatin at 70 mg/m2 intravenously [i.v.] on day 1 and etoposide at 100 mg/m2 i.v. on day 1 and 200 mg/m2 orally on days 2 and 3) or symptomatic treatment. No statistically significant differences in survival time were found between the two treatment techniques. A major problem in the interpretation of the results was the use of semicurative radiation therapy (3000 to 4200 cGy) to the primary tumor and mediastinum, which was given with symptomatic intent. Three long-term survivors were seen in the latter group.", "Current chemotherapy treatment of metastatic non-small cell lung cancer has demonstrated some objective responses, but is still largely palliative. This report reviews the results of a randomized trial in patients with advanced metastatic non-small cell lung cancer which compared treatment with supportive care (treatment with palliative radiation, psychosocial support, analgesics, nutritional support) to supportive care plus combination chemotherapy with cisplatin and vinblastine. Although the patients receiving combination chemotherapy had a slightly longer median survival (20.43 weeks versus 13.57 weeks), it was not statistically significant (P = 0.09). In addition, the patients receiving chemotherapy experienced serious toxicity, and showed no significant benefit in terms of quality of life as measured by Karnofsky performance status score. The authors conclude that contemporary combination chemotherapy provides only modest survival benefit to patients with advanced metastatic non-small cell lung cancer and should not be considered standard therapy. Future investigations of chemotherapy in patients with unresectable non-small cell lung cancer should continue to utilize control arms which provide high-quality supportive care.", "The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).", "Patients with TNM stage IV non-small-cell lung cancer have short survival times. Previous controlled studies comparing chemotherapy and supportive care for the treatment of this type of cancer have not given consistent results, have included patients with different disease stages, and have rarely reported drug dose intensity.\n The present trial was designed to assess the safety and the effect on survival of supportive care alone versus chemotherapy with cisplatin, cyclophosphamide, and mitomycin combined with appropriate supportive care in patients with stage IV non-small-cell lung cancer.\n Patients (n = 102) with stage IV non-small-cell lung cancer were randomly assigned to one of two treatment regimens. The combined modality group (52 patients) received supportive care along with cisplatin (75 mg/m2), cyclophosphamide (400 mg/m2), and mitomycin (10 mg/m2) given intravenously at 3-week intervals. The supportive care group (50 patients) received supportive care alone. Randomization was stratified on the basis of histology (squamous versus nonsquamous cell carcinoma), performance status (Karnofsky), and weight loss (during the 6 months preceding randomization). The two groups were well matched for age and sex. Survival analysis was performed after the last patient died.\n The median number of chemotherapy cycles was 3.5 per patient. Mean weekly delivered doses of drugs were as follows: cisplatin, 22.1 mg/m2; cyclophosphamide, 118 mg/m2; and mitomycin, 2.9 mg/m2. Toxic effects due to chemotherapy were generally mild, but peripheral neuropathy and hematologic and renal toxic effects were observed. In the supportive care group, mean survival was 6.1 months (median, 4.0 months); six patients lived at least 12 months and two lived at least 18 months. In the combined modality group, mean survival was 11.3 months (median, 8.5 months); 20 patients lived at least 12 months, 13 lived at least 18 months, and five lived at least 24 months. Difference in survival was statistically significant (P < .0001). Survival was directly related to initial performance status in both groups (P < .01) and was significantly (P < .01) longer for patients with squamous cell carcinoma than for those with nonsquamous cell carcinoma.\n The combination of supportive care and cisplatin-cyclophosphamide-mitomycin therapy offers a survival advantage over supportive care alone in patients with advanced non-small-cell lung cancer.\n Metastatic non-small-cell lung cancer, generally considered to be unresponsive or marginally responsive to chemotherapy, can be treated with chemotherapy, with an expectation of prolonging patient survival. Although the results of the present study are encouraging, clinical research should continue to be directed toward developing more effective treatments for this disease." ]

[ "7035953", "958261", "10886577", "4574639", "879831", "4191931", "621612", "8159300", "4137139", "8015643", "342654", "16047223", "16222548", "15901972", "4698338", "15015070", "2248508", "4698337" ]

[ "Effect of cytotoxic drugs in frequently relapsing nephrotic syndrome with and without steroid dependence.", "Chlorambucil treatment of frequently relapsing nephrotic syndrome.", "A multicenter trial of mizoribine compared with placebo in children with frequently relapsing nephrotic syndrome.", "Comparative trial of 2 weeks and 8 weeks cyclophosphamide in steroid-sensitive relapsing nephrotic syndrome of childhood.", "Controlled trial of azathioprine in treatment of steroid-responsive nephrotic syndrome of childhood.", "Controlled trial of azathioprine in children with nephrotic syndrome. A report for the international study of kidney disease in children.", "Chlorambucil dosage in frequently relapsing nephrotic syndrome: a controlled clinical trial.", "Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial.", "Prospective, controlled trial of cyclophosphamide therapy in children with nephrotic syndrome. Report of the International study of Kidney Disease in Children.", "Use of levamisole in maintaining remission in steroid-sensitive nephrotic syndrome in children.", "Controlled trial of chlorambucil in frequently relapsing nephrotic syndrome in children (a preliminary report).", "Long-term results of two unconventional agents in steroid-dependent nephrotic children.", "Experience with levamisole in frequently relapsing, steroid-dependent nephrotic syndrome.", "Comparative study of prednisolone alone and prednisolone plus fusidic acid in the treatment of children with steroid-responsive nephrotic syndrome.", "Therapeutic and toxic effects observed with different dosage programs of cyclophosphamide in treatment of steroid-responsive but frequently relapsing nephrotic syndrome.", "Pulse cyclophosphamide therapy in steroid-dependent nephrotic syndrome.", "Eight and 12 week courses of cyclophosphamide in nephrotic syndrome.", "A controlled prospective study of cyclophosphamide in relapsing, corticosteroid-responsive, minimal-lesion nephrotic syndrome in childhood." ]

[ "In a prospective, controlled study, 50 children with frequently relapsing nephrotic syndrome who had steroid toxicity were treated for eight weeks with either cyclophosphamide (2 mg per kilogram of body weight per day) or chlorambucil (0.15 mg per kilogram per day), in combination with prednisone in tapering doses. Of the 34 children shows relapses had tended to occur after the prednisone dosage had been reduced or immediately after the drug was discontinued (the steroid-dependent group), 22 also had early relapses after cytotoxic-drug treatment. In contrast, cytotoxic drug treatment produced long-lasting remissions in 12 of the 16 children whose relapses usually occurred after prednisone treatment had been interrupted for more than 14 days (the non-steroid-dependent group). The difference in response between the two groups was highly significant (P less than 0.001). We conclude that patients with frequent relapses without steroid dependence can be treated successfully with an eight-week course of cytotoxic drugs, whereas those with steroid-dependent nephrotic syndrome do not profit from cytotoxic drugs in the low doses used.", "Chlorambucil, in combination with prednisone, was compared with prednisone alone in a randomized controlled trial in 21 children with either steroid-dependent or frequently relapsing nephrotic syndrome to assess its effect on the duration of remission and the rate of relapse. All control patients treated with prednisone alone continued to relapse at the same rate, with all patients experiencing a return of proteinuria by seven months. Conversely, those who received the same prednisone therapy along with chlorambucil for six to 12 weeks remained in complete remission, without further medication, during 12 to 34 months of follow-up observation. Complications were minimal. Immediate side effects commonly reported with cyclophosphamide were not seen with chlorambucil. Comparison with published reports also suggests that remission induced by chlorambucil is more stable than that after cyclophosphamide. Chlorambucil appears to be of value in the frequently relapsing nephrotic patient, adding an effect that is unattainable with prednisone alone.", "The use of corticosteroids or cytotoxic/immunosuppressive agents such as cyclophosphamide, chlorambucil, and cyclosporine for the treatment of frequently relapsing nephrotic syndrome (FRNS) is limited because of their adverse effects. This study was conducted to evaluate the efficacy and safety of mizoribine, a relatively new immunosuppressive drug developed in Japan, in children with FRNS.\n A double-blind, placebo-controlled, multicenter trial was carried out in children, from 2 to 19 years old, with FRNS. At relapse, patients were treated with prednisolone. According to a dynamic allocation, mizoribine or a placebo was concurrently administered to each patient. Prednisolone was gradually tapered and discontinued within 12 weeks. The test drug was maintained for 48 weeks. The primary end point was the relapse rate (the total number of relapses/the total treatment days for all patients). Analyses were performed according to the intention-to-treat principle.\n The primary analysis was conducted on 99 mizoribine- and 98 placebo-treated patients. The relapse rate was lower in the mizoribine group than in the placebo group (0.0055 vs. 0.0067; ratio 0.81, 95% CI, 0.61 to 1.05, P = 0.12). The hazard ratio of the cumulative remission rate between the two groups was 0.79 (95% CI, 0. 57 to 1.08). In the subgroups consisting of patients 10 years old or younger, the relapse rate ratio between the mizoribine subgroup (54 patients) and the placebo subgroup (57 patients) was 0.66 (95% CI, 0. 44 to 0.94, P = 0.017). The hazard ratio of the cumulative remission rate between the two subgroups was 0.56 (95% CI, 0.37 to 0.85, P = 0. 007). Hyperuricemia was the most common adverse event with mizoribine (16%), but was transient.\n Compared with the placebo, mizoribine significantly decreased the relapse rate and prolonged the remission period in the subgroup consisting of patients 10 years old or younger. This drug may be useful in young children with FRNS who generally relapse more frequently than older children.", "nan", "A controlled trial of azathioprine treatment of steroid-responsive frequent-relapsing nephrotic syndrome of childhood failed to show a therapeutic effect on the stability of remission after withdrawal of corticosteroid treatment.", "nan", "A controlled clinical trial was performed using two dosage regimens of chlorambucil to treat children with frequently relapsing nephrotic syndrome. All children concurrently received prednisone (60 mg/m2 on alternate days). Ten children (Group I) were given chlorambucil as a stable dose (0.2 mg/kg/day) for 56 to 60 days, and 11 children (Group II) received increasing doses (0.2 to 0.63 mg/kg/day) for 42 to 77 days. Two children in each group subsequently relapsed. Follow-up averaged 28.6 and 27.2 months in Groups I and II, respectively. Three children in Group II developed infectious complications. The data indicate that a stable dosage regimen for chlorambucil is as effective as an increasing dose regimen in achieving long-term remission of frequently relapsing nephrotic syndrome.", "To compare the efficacy (maintenance of remission), safety and tolerability of cyclosporin (CsA) with those of cyclophosphamide in patients with steroid-dependent or frequently relapsing nephrotic syndrome (NS).\n Open, prospective, randomized, multicentre, controlled study for parallel groups, stratified for adults and children. The setting was in nephrological departments in Italy.\n Seventy-three patients with steroid-sensitive idiopathic NS admitted to the study were randomly assigned to cyclophosphamide (2.5 mg/kg/day) for 8 weeks or CsA (5 mg/kg/day in adults, 6 mg/kg/day in children) for 9 months, tapered off by 25% every month until complete discontinuation at month 12. Seven patients lost to follow up were not considered in the analysis. The remaining 66 patients were followed up for 3-24 months after randomization.\n Relapse-free survival; number of N.S. relapses/patient/year; cumulative dose of prednisone/patient; laboratory investigations (kidney and liver functions, haematological parameters); incidence of adverse events.\n At month 9, 26 of 35 CsA-treated patients were still in complete remission and a further five patients were in partial remission; 18 of 28 cyclophosphamide-treated patients were in complete remission, and one in partial remission (P = NS). No difference between adults and children was seen with either treatment. The risk of relapse was similar between frequent relapsers (19 of 22) and steroid-dependent patients (8 of 14) given CsA, and those given cyclophosphamide (5 of 15 and 6 of 15). The mean number of relapses per year and the mean dose of prednisone per year were significantly less (P < 0.001) in both groups for the experimental year than for the year before randomization. At 2 years, 25% of the patients given CsA (50% adults and 20% children) and 63% of those given cyclophosphamide (40% adults and 68% children) had not had any relapse of NS. Tolerance to the two drugs was generally good. The CsA-related side-effects were mild and disappeared after drug discontinuation.\n This study shows that both treatments are effective and well tolerated; more patients given cyclophosphamide had stable remissions.", "nan", "A randomized, controlled trial was conducted in a pediatric unit in a teaching hospital in India to assess the efficacy of levamisole in maintaining remission in children with steroid-sensitive nephrotic syndrome. Sixty-one children with steroid-sensitive nephrotic syndrome, who had achieved remission with corticosteroids, were allocated to a treatment group (33 patients) receiving levamisole (2-3 mg/kg/day) twice a week for 12 months or to a control group (28 patients) receiving no treatment. The main outcome measure was duration of remission. Thirty months later, in the levamisole group, 21 of 33 patients were in remission as against 12 of 28 patients in the control group (chi 2 = 2.54, p = 0.11, NS). The median duration of remission maintenance was 12 months in the levamisole group as compared with 10.5 months in the control group. On survival analysis, the difference in duration of remission maintenance between the two groups was not significant (p = 0.10), though there was a trend in favor of the treatment group. On stratified survival analysis, multiple relapsers in the levamisole group had longer remission maintenance than the control group though this did not reach statistical significance (p = 0.08). The clinically significant trend towards increased duration of remission maintenance in steroid-sensitive nephrotic syndrome observed with levamisole therapy, especially in patients with multiple relapses, may require a larger study with a longer follow-up for definitive confirmation.", "nan", "Children with steroid-dependent minimal change nephrotic syndrome are prone to serious steroid side effects. Alternative therapies, such as oral cyclophosphamide, may also have serious side effects. We conducted this novel prospective study to compare the long-term efficacies of levamisole and I.V. pulse cyclophosphamide as therapies with potentially fewer side effects. This study included 40 children with idiopathic steroid-dependent minimal change nephrotic syndrome (age 3-15 years; 31 boys and 9 girls). The patients were randomized into two equal groups. One group received levamisole 2.5 mg/kg on alternate days (levamisole group) while the other group received I.V. cyclophosphamide 500 mg/m2/month for six months (cyclophosphamide group). Prednisolone was gradually withdrawn. After stopping treatment, the number of patients that maintained remission was five (25%) in each group at six months, four (20%) versus two (10%) at one year and three (15%) versus one (5%) at two years in the levamisole and cyclophosphamide groups respectively, and one (5%) in each group at three and four years. The overall side effects were mild and both drugs were well tolerated. In view of the results, we recommend trial of levamisole before adopting other therapies with more serious side effects in such patients.", "This was a controlled prospective study on the use of an immunomodulator drug, levamisole, in the treatment of frequently relapsing, steroid-dependent (FR/SD) idiopathic nephrotic syndrome. The study was started on 1 January 2001 and completed on 31 December 2003. There were two groups: a treatment group who received levamisole (2.5 mg/kg) on alternate days for 1 year and a control group who received low-dose prednisolone only (<0.5 mg/kg) on alternate days for 1 year. There were a total of 56 patients (32 in the treatment group and 24 in the control group). The male to female ratio was 1.66:1 in both groups. The mean age upon initial diagnosis was 3.3 years in the levamisole group versus 4.3 years in the control group. The mean duration from diagnosis to the start of the second line treatment was 3.2 years in the levamisole group versus 2.8 years in the control group. The relapse rate and the total cumulative dose of prednisolone during the year prior to second line therapy was compared to that during the year following the institution of second line therapy in 56 patients. The mean relapse rate was reduced more significantly in the levamisole group. It was reduced by 0.29 versus 0.11 relapses/patient/month in the control group (P =0.0001). The mean cumulative dose of steroids was also reduced more significantly in the levamisole group. It was reduced by 293 versus 102 mg/m(2)/month in the control group (P <0.0001). Therapy failure was seen in 3/32 (9.4%) in the levamisole group versus 12/24 (50%) in the control group. Of the patients, 20/32 (62.5%) using levamisole were relapse-free in the follow-up year post therapy, while no patient was relapse-free in the control group over the same period. No major adverse effects of levamisole were seen. The cost of levamisole therapy was estimated to be US$ 25 per year for a 20-kg body weight child. Thus, we concluded that levamisole is a highly efficacious, safe and easily affordable initial therapy for FR/SD idiopathic nephrotic syndrome.", "There are several reports in the literature indicating that fusidic acid owns functions similar to those of cyclosporin. As cyclosporin has effectively been used in frequently relapsing steroid-responsive nephrotic syndrome we carried out this study to determine whether fusidic acid used along with prednisolone diminishes rate of steroid-responsive nephrotic syndrome relapses in children.\n The patients were randomly allocated to receive either prednisolone alone or prednisolone plus fusidic acid for two months in standard doses. In the cases of relapses the treatment was changed to the comparative treatment method. Altogether 18 children (12 boys and 6 girls) aged 1.3 to 13.2 years entered the study. Thirteen of them were treated by either method on different occasions, four patients were treated with prednisolone only, and one child was treated with prednisolone plus fusidic acid only. Thus, there were 17 evaluable treatment courses with prednisolone alone and 14 courses with prednisolone plus fusidic acid. The patients were followed-up as long as the remission lasted.\n There was prompt and complete response under the influence of both treatment methods. However, relapses occurred in all the patients irrespective of the mode of treatment. Mean duration of remissions did not differ significantly between the study groups (17.8+/-20.4 weeks in the prednisolone group and 18.3+/-23.9 weeks in the prednisolone plus fusidic acid group; p>0.05). There were no statistically significant differences in laboratory parameters reflecting therapeutic efficacy in the comparative treatment groups, too.\n Thus, it was not revealed any remission-sustaining efficacy of fusidic acid used in standard doses for two months along with prednisolone in children with frequently relapsing steroid-responsive nephrotic syndrome.", "nan", "Intravenous cyclophosphamide (IVCP) has been shown to be effective in lupus nephritis. This is a randomized controlled trial to compare the effectiveness of IVCP with oral cyclophosphamide (OCP) in patients with steroid-dependent (SD) idiopathic nephrotic syndrome (INS). Forty-seven consecutive children who were SD were randomized to receive either OCP (2 mg/kg per dayx12 weeks) or IVCP (500 mg/m(2) per month IVx6 months) after achieving a steroid-induced remission. The response was evaluated in terms of remission, change in steroid response status, duration of remission (i.e., proteinuria-free days), side effects, and compliance. Of the 47, IVCP was given to 26 children and OCP to 21 children. The demographic data, histopathology, biochemical profile, and duration of follow-up in the two groups were similar. On Kaplan-Meier survival analysis, the median proteinura-free time was 360+/-88 days compared with 96+/-88 days in the OCP group (values median+/-SE, log rank P=0.05). The actuarial cumulative sustained remission in our study was 73% in IVCP compared with 38.1% in OCP at 6 months after therapy, but was almost identical (18.6% in IVCP vs. 19%in OCP) after 2 years. Thus in our study the overall improvement in steroid response category from SD to sustained remission, infrequent relapser, and frequent relapser (88% in IVCP vs. 57% in OCP) was significantly better in the IVCP group, although the number of children with persistent remission tended to be similar at 2 years. Furthermore, the response was observed with a 40% lower cumulative dose than OCP. Hence, we conclude that IVCP is a safe and effective therapeutic modality in children with INS who are SD.", "Seventy-three children with steroid dependent minimal change nephrotic syndrome were randomly allocated to receive treatment with cyclophosphamide (2 mg/kg/day) for either eight or 12 weeks, in combination with prednisolone. All patients had previously relapsed while the dosage was being reduced or within 14 days of discontinuing prednisolone in the six months before receiving cyclophosphamide treatment (steroid dependent), and had severe steroid toxicity. Thirty two patients were treated with cyclophosphamide for eight weeks, and 41 for 12 weeks. There were no differences between the two groups in age at onset of nephrosis or entry into the study, sex ratio, duration of nephrosis, number of relapses before entry, and follow up period after entry. The relapse free rate of patients treated for eight weeks (25%) was similar to that of those treated for 12 weeks (24%) five years after stopping the treatment, and the mean relapse free interval and the sparing effect of cyclophosphamide (if any) on subsequent treatment with steroids did not differ between the groups. We conclude that cyclophosphamide should be used for no longer than eight weeks at a dose of 2 mg/kg/day in children with steroid dependent minimal change nephrotic syndrome.", "nan" ]

[ "15465981", "16585435", "16762371", "14609804", "15600384", "10711911", "17728106", "16818861", "16102942", "15667429", "17022791", "15578006", "12729882", "15076013", "16754835", "17113759", "15358979", "17662577", "14971863", "11329400", "9315992", "16633144", "16974184", "17065975", "11823268", "12755665", "15276691", "16199834", "14583740", "16783811", "17151160", "17606657", "11163780", "14687871", "16585434" ]

[ "Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder.", "Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic.", "Efficacy of risperidone versus olanzapine in patients with schizophrenia previously on chronic conventional antipsychotic therapy: a switch study.", "International multisite double-blind trial of the atypical antipsychotics risperidone and olanzapine in 175 elderly patients with chronic schizophrenia.", "A comparison of weight change during treatment with olanzapine or aripiprazole: results from a randomized, double-blind study.", "Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone, or haloperidol. The Canadian Collaborative Group for research in schizophrenia.", "Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine.", "Childhood-onset schizophrenia: A double-blind, randomized clozapine-olanzapine comparison.", "Olanzapine versus risperidone in the treatment of post-psychotic depression in schizophrenic patients.", "Randomized double blind comparison of olanzapine vs. clozapine on subjective well-being and clinical outcome in patients with schizophrenia.", "The treatment of negative symptoms and deficit states of chronic schizophrenia: olanzapine compared to amisulpride and placebo in a 6-month double-blind controlled clinical trial.", "Cognitive improvement in schizophrenic patients does not require a serotonergic mechanism: randomized controlled trial of olanzapine vs amisulpride.", "Olanzapine vs risperidone in the management of schizophrenia: a randomized double-blind trial in Australia and New Zealand.", "A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia.", "Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder.", "A double-blind randomised comparative trial of amisulpride versus olanzapine for 2 months in the treatment of subjects with schizophrenia and comorbid depression.", "Cerebral D2 and 5-HT2 receptor occupancy in Schizophrenic patients treated with olanzapine or clozapine.", "Effects of olanzapine, risperidone and haloperidol on prepulse inhibition in schizophrenia patients: a double-blind, randomized controlled trial.", "Adverse effects and laboratory parameters of high-dose olanzapine vs. clozapine in treatment-resistant schizophrenia.", "A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder.", "Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders.", "A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms.", "Randomized, double-blind 6-month comparison of olanzapine and quetiapine in patients with schizophrenia or schizoaffective disorder with prominent negative symptoms and poor functioning.", "Efficacy of olanzapine and risperidone in schizophrenia: a randomized double-blind crossover design.", "Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder.", "Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics.", "Effect of switching to atypical antipsychotics on memory in patients with chronic schizophrenia.", "Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia.", "A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double-blind, randomized, 8-week trial.", "Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophrenia.", "Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes.", "Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison.", "Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine.", "Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia.", "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment." ]

[ "Limited randomized, controlled trial data exist on possible differences between atypical antipsychotics in efficacy, overall tolerability, and important indices of health status. The authors compared the efficacy and tolerability of ziprasidone and olanzapine in the treatment of acutely ill inpatients with schizophrenia or schizoaffective disorder.\n In this 6-week, multicenter, double-blind, parallel-design, flexible-dose trial, patients were randomly assigned to receive ziprasidone (N=136) or olanzapine (N=133). Primary efficacy measures were improvement in Brief Psychiatric Rating Scale and Clinical Global Impression (CGI) severity scale scores; secondary measures were scores on the CGI improvement scale, Positive and Negative Syndrome Scale, and Calgary Depression Scale for Schizophrenia. Tolerability assessments included fasting lipid profiles, fasting glucose and insulin measurements, electrocardiography, and monitoring of vital signs and body weight.\n The overall mean daily doses were 129.9 mg (SD=27.3) for ziprasidone and 11.3 mg (SD=2.8) for olanzapine. Both antipsychotics were efficacious in improving symptoms and global illness severity. The two treatment groups did not differ significantly in primary or secondary efficacy measures at endpoint or in by-visit analysis. Both agents were well tolerated. Body weight, total cholesterol, triglycerides, and low-density lipoprotein cholesterol significantly increased with olanzapine but not with ziprasidone; all between-group comparisons of these variables were significant and favored ziprasidone. Olanzapine, but not ziprasidone, was associated with significant increases in fasting insulin level. No patient in either group exhibited a corrected QT interval >/=500 msec.\n During 6 weeks' treatment, ziprasidone and olanzapine demonstrated comparable antipsychotic efficacy. Differences favoring ziprasidone were observed in metabolic parameters.", "In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic.\n Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason.\n The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168).\n Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.", "The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug. Thirty-six subjects with schizophrenia spectrum disorder, on conventional antipsychotic medication therapy for at least 2 years, were randomized in double-blind fashion to risperidone versus olanzapine. Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated, followed by tapering and discontinuation of conventional antipsychotic medication. Atypical antipsychotic agents were then administered alone (monotherapy) for 12 weeks. Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, and Simpson Angus Scale. Body weight was measured at each visit. Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint (22 weeks) [risperidone: baseline=59.3 (SE 3.1), 22 weeks=44.3 (SE 2.3) (p<0.001); olanzapine: baseline=55.9 (SE 3.3), 22 weeks=46.9 (SE 3.2) (p<0.001). Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts. Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression. Of note, while positive factor scores exhibited the majority of change within the first 10 weeks, negative factor scores continued to decline significantly in both treatment groups throughout the study. Tolerability assessments did not differ between groups. The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents.", "The authors compared the effects of the two most commonly used atypical antipsychotics, risperidone and olanzapine, in elderly patients with schizophrenia.\n In an 8-week, international, double-blind study, patients (outpatients, hospital inpatients, and residents of nursing or boarding homes) were randomly assigned to receive risperidone (1 mg to 3 mg/day) or olanzapine (5 mg to 20 mg/day). The main outcome measures were changes in Positive and Negative Syndrome Scale (PANSS) total scores and rates of extrapyramidal symptoms (EPS).\n Subjects were 175 patients age 60 years or over with schizophrenia or schizoaffective disorder. The mean duration of illness was 36.5 years. Median doses were 2 mg/day of risperidone and 10 mg/day of olanzapine. PANSS total scores and four of the five PANSS factor scores (positive symptoms, negative symptoms, disorganized thoughts, and anxiety/depression) improved significantly at all time-points and at endpoint in both groups; between-treatment differences were not significant. EPS-related adverse events were reported by 9.2% of patients in the risperidone group and 15.9% in the olanzapine group; the between-treatment difference was not significant. Total scores on the Extrapyramidal Symptom Rating Scale were reduced in both groups at endpoint; between-treatment differences were not significant. Clinically relevant weight gain was seen in both groups, but was significantly less frequent in risperidone patients than in olanzapine patients.\n Stable elderly patients with chronic schizophrenia receiving appropriate doses of risperidone or olanzapine over an 8-week period experienced significant reductions in the severity of psychotic and extrapyramidal symptoms, with a relatively low risk of side effects.", "Weight gain is a side effect of therapy with many atypical antipsychotics and may have important clinical repercussions with respect to long-term health and treatment compliance. The primary objective of this double-blind study was to compare the safety and tolerability of aripiprazole and olanzapine in patients with schizophrenia as evidenced by the percentage of patients exhibiting significant weight gain.\n This was a 26-week, multicenter, randomized, double-blind, active-controlled trial in patients with DSM-IV schizophrenia who were in acute relapse and required hospitalization. Significant weight gain was defined as a > or = 7% increase in body weight from baseline. Body weight, Positive and Negative Syndrome Scale, and Clinical Global Impressions-Improvement scale (CGI-I) assessments were performed at baseline and at regular intervals during the study. The study period was from April 2000 through June 2001.\n 317 patients were randomly assigned to aripiprazole (N = 156) or olanzapine (N = 161). Compared with those treated with aripiprazole, a greater proportion of patients treated with olanzapine exhibited clinically significant weight gain during the trial. By week 26, 37% of olanzapine-treated patients had experienced significant weight gain compared with 14% of aripiprazole-treated patients (p < .001). Statistically significant differences in mean weight change were observed between treatments beginning at week 1 and sustained throughout the study. At week 26, there was a mean weight loss of 1.37 kg (3.04 lb) with aripiprazole compared with a mean increase of 4.23 kg (9.40 lb) with olanzapine among patients who remained on therapy (p < .001). Changes in fasting plasma levels of total cholesterol, high-density lipoprotein cholesterol, and triglycerides were significantly different in the 2 treatment groups, with worsening of the lipid profile among patients treated with olanzapine. There was a consistent and sustained improvement in symptoms in patients who remained on therapy with either olanzapine or aripiprazole as assessed by CGI-I scores and responder rates throughout the study.\n Olanzapine had a greater impact on patients' weight than aripiprazole. Significant differences in favor of aripiprazole were also observed in the effects of therapy on plasma lipid profile. Both treatment groups achieved comparable clinically meaningful improvements on efficacy measures. The observed effects on weight and lipids indicate a potentially lower metabolic and cardiovascular risk in patients treated with aripiprazole compared with those treated with olanzapine.", "The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia.\n Sixty-five patients in this multicenter double-blind study were randomly assigned to olanzapine (5-20 mg), risperidone (4-10 mg), or haloperidol (5-20 mg). Standard measures of clinical and motor syndromes were administered, as well as a comprehensive battery of tests to assess (1) motor skills, (2) attention span, (3) verbal fluency and reasoning, (4) nonverbal fluency and construction, (5) executive skills, and (6) immediate recall at baseline and after 6, 30, and 54 weeks of treatment.\n The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone, but no significant difference was shown between risperidone and haloperidol. The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment. Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain, and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test.\n These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone. A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implications of this change to cerebral function and quality of life for people with schizophrenia.", "Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure.\n The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia.\n In a prospective, rater-blinded study, 86 participants were randomized to receive either olanzapine or quetiapine, and assessed at baseline and after 3, 6, 9 and 12 months. Outcome measures included, besides symptoms and side effects rating scales, the subjective scale to investigate cognition in schizophrenia (SSTICS), a computer-assisted cognitive test battery (COGLAB), the sickness impact profile (SIP), the global assessment of functioning (GAF) scale, and the drug attitude inventory (DAI).\n Both olanzapine and quetiapine were equally effective in improving symptom severity and decreasing the neurological side effects. Quetiapine was significantly better tolerated (p=0.002), improved self-rated cognitive dysfunction (p=0.002) and subjects' performance on selected neurocognitive tasks (p=0.01). Olanzapine use was associated with greater symptom stability, fewer drop outs (p=0.01) and frequent metabolic aberrations (p=0.001). The accrued benefits of drug therapy, however, were not reflected as significant gains in daily functioning and quality of life.\n Quetiapine is noted to have specific cognition enhancing properties in schizophrenia that warrants further exploration. The observed clinical and cognitive benefits associated with quetiapine may likely be attributable to its loose binding to, and fast dissociation from the dopamine receptors. Olanzapine has proved to be a reliable antipsychotic drug with a greater liability to cause metabolic abnormalities.", "Childhood-onset schizophrenia is a rare but severe form of the disorder that is frequently treatment resistant. The psychiatrist has a limited evidence base to guide treatment, particularly as there are no trials in children comparing atypical antipsychotics, the mainstay of current treatment.\n To compare the efficacy and safety of olanzapine and clozapine, hypothesizing that clozapine would be more efficacious.\n Double-blind randomized 8-week controlled trial, with a 2-year open-label follow-up.\n National Institute of Mental Health study, January 1998 to June 2005. Patients underwent reassessment 2 years after discharge.\n Children and adolescents recruited nationally, aged 7 to 16 years, meeting unmodified DSM-IV criteria for schizophrenia, and resistant to treatment with at least 2 antipsychotics.\n After drug washout and a 1- to 3-week antipsychotic-free period, patients were randomized to treatment with clozapine (n = 12) or olanzapine (n = 13).\n The Clinical Global Impression Severity of Symptoms Scale and Schedule for the Assessment of Negative/Positive Symptoms.\n Clozapine was associated with a significant reduction in all outcome measures, whereas olanzapine showed a less consistent profile of clinical improvement. While there were moderate to large differential treatment effects in favor of clozapine, these reached significance only in the alleviation of negative symptoms from an antipsychotic-free baseline (P = .04; effect size, 0.89). Clozapine was associated with more overall adverse events. At 2-year follow-up, 15 patients were receiving clozapine with evidence of sustained clinical improvement, but additional adverse events emerged, including lipid anomalies (n = 6) and seizures (n = 1).\n While not demonstrating definitively the superiority of clozapine compared with olanzapine in treatment-refractory childhood-onset schizophrenia, the study suggests that clozapine has a more favorable profile of clinical response, which is balanced against more associated adverse events.", "To compare the efficacy of two atypical antipsychotic drugs, olanzapine and risperidone, in schizophrenic patients with post-psychotic depression.\n A clinically significant decrease of MADRS scores occurred in patients treated with both drugs for 8 weeks.\n Atypical antipsychotic drugs may be particularly appropriate when treating schizophrenic patients with depression.", "This randomized double-blind multicenter trial evaluated the effects of olanzapine vs. clozapine on subjective well-being, quality of life (QOL) and clinical outcome.\n The primary objective was to demonstrate non-inferiority of olanzapine, mean dosage 16.2 +/- 4.8 (5-25 mg/day) vs. clozapine, mean dosage 209 +/- 91 (100-400 mg/day) regarding improvement on the 'Subjective Well-Being under Neuroleptic Treatment' (SWN) Scale after 26 treatment weeks in 114 patients with schizophrenia. Secondary outcome parameters included: Munich QOL Dimension List (MLDL), Positive and Negative Symptom Scale (PANSS), Clinical Global Impression (CGI).\n SWN scores improved significantly in both groups, olanzapine was non-inferior to clozapine (group difference 3.2 points in favor of olanzapine; 95% CI: 4.2;10.5). MLDL-satisfaction, PANSS and CGI-S improved similarly, olanzapine yielded a higher CGI Therapeutic Index. Individual SWN and PANSS changes correlated only moderately (r = -0.45).\n Olanzapine was non-inferior to clozapine. The lack of a marked correlation between PANSS and SWN improvements indicates that patients and psychiatrists perceive treatment differently.", "The aim of the study was to evaluate the efficacy of olanzapine (5 and 20 mg/day) over a 6-month period in chronic schizophrenic patients experiencing predominantly negative symptoms.\n Two hundred and forty-four patients participated in a 6-month multicenter double-blind trial of placebo (n = 34), olanzapine 5 mg/day (n = 70), olanzapine 20 mg/day (n = 70), or amisulpride 150 mg/day (n = 70). Primary measure was the scale for the assessment of negative symptoms.\n Olanzapine 5 mg/day showed significantly greater improvement than placebo in negative symptoms and in the Positive and Negative Syndrome Scale total score. Baseline positive symptoms were low at baseline and changed minimally. The neurological tolerance of olanzapine, amisulpride and placebo were comparable.\n Olanzapine 5 mg/day was effective in treating negative symptoms in a group of schizophrenic with predominantly negative symptoms during the stabilization phase. Improvement in positive symptoms or extrapyramidal symptoms (EPS) was unlikely to explain this result while improvement in depression may have partially contributed.", "Combined serotonin-2A (5-HT(2A)) and dopamine-2 (D2) receptor blockade has been proposed as a candidate mechanism by which second-generation antipsychotics (SGAs) improve both cognition and negative symptoms in schizophrenic patients, in contrast to antipsychotics of the first generation. The SGA amisulpride, however, only binds to D2/D3 receptors, which makes it an interesting tool to test this assumption. In a randomized controlled trial, 52 schizophrenic patients were allocated to treatment with either olanzapine (10-20 mg/day) or amisulpride (400-800 mg/day). A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks. Cognitive improvements of moderate size were observed, with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs. Importantly, amisulpride was not inferior to olanzapine for any cognitive domain. Combined 5-HT(2A)/D2 receptor blockade is probably not necessary for cognitive improvement by SGAs.", "Improved drug therapy for schizophrenia may represent the best strategy for reducing the costs of schizophrenia and the recurrent chronic course of the disease. Olanzapine and risperidone are atypical antipsychotic agents developed to meet this need. We report a multicenter, double-blind, parallel, 30-week study designed to compare the efficacy, safety, and associated resource use for olanzapine and risperidone in Australia and New Zealand. The study sample consisted of 65 patients who met DSM-IV criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder. Olanzapine-treated patients showed a significantly greater reduction in Positive and Negative Syndrome Scale (PANSS) total, Brief Psychiatric Rating Scale (BPRS) total, and PANSS General Psychopathology scores at endpoint compared to the risperidone-treated patients. Response rates through 30 weeks showed a significantly greater proportion of olanzapine-treated patients had achieved a 20% or greater improvement in their PANSS total score compared to risperidone-treated patients. Olanzapine and risperidone were equivalent in their improvement of PANSS positive and negative scores and Clinical Global Impression-Severity of Illness scale (CGI-S) at endpoint. Using generic and disease-specific measures of quality of life, olanzapine-treated patients showed significant within-group improvement in most measures, and significant differences were observed in favor of olanzapine over risperidone in Quality of Life Scale (QLS) Intrapsychic Foundation and Medical Outcomes Study Short Form 36-item instrument (SF-36) Role Functioning Limitations-Emotional subscale scores. Despite the relatively small sample size, our study suggests that olanzapine has a superior risk:benefit profile compared to risperidone.", "Atypical antipsychotics offer advantages over earlier drugs for the treatment of schizophrenia, although few data exist on the relative merits of different atypical antipsychotics. A multicentre, double-blind, randomized trial was performed to compare amisulpride and olanzapine in the treatment of acute schizophrenia. Adult schizophrenic patients with dominant positive symptomatology received amisulpride (200-800 mg/day) or olanzapine (5-20 mg/day) for 6 months. The primary efficacy variable was change from baseline of the Brief Psychiatric Rating Scale (BPRS) score, assessed with a non-inferiority analysis. The evolution of positive and negative symptomatology, depression, social functioning and quality of life were assessed. Safety evaluation included adverse event reporting, neurological status and body weight. The improvement of BPRS score was 32.7% in the amisulpride group and 33.0% in the olanzapine group; thus, the efficacy of amisulpride was not inferior to that of olanzapine. All other secondary efficacy outcome variables evolved to a similar extent in both groups. Adverse event frequency was similar in both groups. Amenorrhoea was encountered only in the amisulpride group (6.2% of patients), whereas elevations of liver transaminases were more frequent in the olanzapine group (17% versus 3.7% of patients). The incidence and mean extent of clinically relevant weight gain were higher in the olanzapine group (35.1% and 3.9 kg) than in the amisulpride group (20.6% and 1.6 kg). The efficacy of amisulpride is not inferior to that of olanzapine in the treatment of acute schizophrenia. The side-effect profile of the two drugs differed.", "Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance.\n To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.\n Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36).\n Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS).\n Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales.\n Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.", "To compare the efficacy and safety of amisulpride and olanzapine in subjects with schizophrenia and comorbid depression in a randomised double-blind trial.\n Eighty-five adult patients fulfilling DSM-IV criteria for schizophrenia and presenting a depressive episode were randomised to amisulpride (200-600 mg/day) or olanzapine (5-15 mg/day) for 8 weeks. Primary efficacy variables were change in Calgary Depression Scale (CDS) score and Clinical Global Impression (CGI) of Change. Safety was monitored by adverse event reporting and determination of extrapyramidal function and metabolic variables.\n The mean change from baseline of CDS score was -6.84 in the amisulpride group and -7.36 in the olanzapine group. 65.9% and 61.5% of subjects, respectively, were considered \"much\" or \"very much\" improved. No significant inter-group difference in effect size was observed. The frequency of adverse events was low and emergence of extrapyramidal symptoms was not seen. Four patients in the olanzapine group developed abnormal triglyceride levels. Mean weight gain was 1.45 and 0.5 kg, respectively, in the olanzapine and amisulpride groups.\n Amisulpride and olanzapine are effective in patients with schizophrenia and comorbid depression. Tolerance of both drugs was acceptable, although use of olanzapine was associated with a trend toward greater metabolic side-effects .", "We report the results of a double-blind, randomized prospective trial on D2 and 5-HT2 receptor occupancy and the clinical effects of olanzapine versus clozapine in a sample of neuroleptic-refractory schizophrenic patients. Receptor occupancy was evaluated in different cortical areas and in basal ganglia using [18F] fluoro-ethyl-spiperone ([18F] FESP) and positron emission tomography (PET). A total of 15 neuroleptic-free patients completed the study undergoing a baseline and a post-treatment PET scan (olanzapine, nine patients, one female; clozapine, six patients, three female) 8 weeks after starting treatment. PET data were analysed both by regions of interest and on a voxel-by-voxel basis using Statistical Parametric Mapping (SPM96). Olanzapine and clozapine induced a similar and significant inhibition of [18F] FESP binding index in the cortex. In the basal ganglia, receptor occupancy was significantly higher with olanzapine than with clozapine (p=0.0018). By contrast, no differences in receptor occupancy were detected at the level of the pituitary gland. Clinical outcomes, in particular a full extra pyramidal tolerability, were similar. In this sample of neuroleptic-refractory schizophrenic patients, olanzapine and clozapine showed a different pattern of occupancy of D2-like receptor despite a common lack of extrapyramidal side-effects.", "Prepulse inhibition (PPI), whereby the startle eyeblink response is inhibited by a relatively weak non-startling stimulus preceding the powerful startle eliciting stimulus, is a measure of sensorimotor gating and has been shown to be deficient in schizophrenia patients. There is considerable interest in whether conventional and/or atypical antipsychotic medications can \"normalize\" PPI deficits in schizophrenia patients. 51 schizophrenia patients participated in a randomized, double-blind controlled trial on the effects of three commonly-prescribed antipsychotic medications (risperidone, olanzapine, or haloperidol) on PPI, startle habituation, and startle reactivity. Patients were tested at baseline, Week 4 and Week 8. Mixed model regression analyses revealed that olanzapine significantly improved PPI from Week 4 to Week 8, and that at Week 8 patients receiving olanzapine produced significantly greater PPI than those receiving risperidone, but not haloperidol. There were no effects of medication on startle habituation or startle reactivity. These results support the conclusion that olanzapine effectively increased PPI in schizophrenia patients, but that risperidone and haloperidol had no such effects. The results are discussed in terms of animal models, neural substrates, and treatment implications.", "Patients with treatment-resistant schizophrenia pose a major challenge to caregivers since only clozapine is documented as having superior efficacy in this population. Although olanzapine is similar to clozapine in structure and receptor profile, it has not been proven to have superior efficacy for this patient group. Nonetheless, olanzapine is being increasingly used in higher doses as clinicians attempt to find a more effective and tolerable therapy for refractory patients. Furthermore, there are little data comparing olanzapine and clozapine in this population. Thirteen patients participated in a randomized double-blind 16-week crossover study of clozapine therapy (450 mg/day) compared to high doses of olanzapine (50 mg/day). No patients on olanzapine responded while 20% responded to clozapine treatment. Olanzapine patients tended to experience higher rates of anticholinergic effects such as dry mouth (80 vs. 20%) and blurry vision (40 vs. 0%). Clozapine-treated patients had higher rates of sialorrhea (80 vs. 10%), sweating (50 vs. 10%), dyspepsia (70 vs. 30%), and lethargy (90 vs. 60%). Neither treatment was associated with significant akathisia. Liver enzyme elevation and lipids were higher with clozapine treatment. Mean weight gain in the initial 8 weeks was 3.4 kg for olanzapine and 1.2 kg for clozapine. High doses of olanzapine during 8 weeks of treatment did not increase lipids and liver enzymes like clozapine did. Olanzapine at 50 mg/day may be associated with more anticholinergic effects and weight gain than clozapine.", "The safety and efficacy of risperidone and olanzapine were compared in a double-blind trial that used doses widely accepted in clinical practice.\n Subjects (N=377) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were randomly assigned to receive 2-6 mg/day of risperidone (mean modal dose=4.8 mg/day) or 5-20 mg/day of olanzapine (mean modal dose=12.4 mg/day) for 8 weeks.\n The two study groups were similar at baseline except that the olanzapine group was slightly younger than the risperidone group. Seventy-five percent of the participants completed the trial, with no between-treatment differences in the proportion of dropouts. Similar proportions of the risperidone and olanzapine groups reported extrapyramidal symptoms (24% and 20%, respectively). Severity of extrapyramidal symptoms was low in both groups, with no between-group differences. Total Positive and Negative Syndrome Scale scores and scores on the five Positive and Negative Syndrome Scale factors were improved in both groups at week 8 (subjects who completed the study) and endpoint (all subjects, including dropouts). There were overall between-treatment differences in efficacy. Comparison of individual factors found no significant differences at endpoint; at week 8, however, improvements on Positive and Negative Syndrome Scale factors for positive symptoms and anxiety/depression were greater with risperidone than olanzapine. An increase in body weight of > or =7% was seen in 27% of olanzapine participants and 12% of risperidone participants.\n Both treatments were well tolerated and efficacious. The frequency and severity of extrapyramidal symptoms were similar in the two treatment groups. Greater reductions in severity of positive and affective symptoms were seen with risperidone than with olanzapine treatment among study completers. There was no measure on which olanzapine was superior. Greater weight gain was associated with olanzapine than with risperidone treatment.", "Olanzapine and risperidone, both second-generation antipsychotic agents, represent two different pharmacologic strategies. Although they share some in vitro properties, they differ by virtue of their chemical structure, spectrum of receptor binding affinities, animal neuropharmacology, pharmacokinetics, and in vivo neuroimaging profile. Based on such differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothesis, an international, multicenter, double-blind, parallel-group, 28-week prospective study was conducted with 339 patients who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms. However, olanzapine demonstrated significantly greater efficacy in negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (> or = 40% decrease in the Positive and Negative Syndrome Scale total score). Furthermore, a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves. The incidence of extrapyramidal side effects, hyperprolactinemia, and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients. In addition, statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a controlled, clinical investigation. Olanzapine seemed to have a risk-versus-benefit advantage.", "The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms.\n This randomized, double-blind, 24-week, fixed-dose study compared olanzapine (n = 202) and ziprasidone (n = 192) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms. Outcome measures included change in Calgary Depression Scale for Schizophrenia (CDSS) score from baseline to 8 weeks (primary outcome) and changes in CDSS, Montgomery-Asberg Depression Rating Scales, Positive and Negative Syndrome Scale, and Global Assessment of Functioning (GAF) scores for 24 weeks. Statistical analyses included mixed-effects model repeated measures (primary analysis) and change from baseline to last observation carried forward (LOCF).\n At baseline, patients had moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scales total score, 27.3). For 8 weeks, patients treated with olanzapine or ziprasidone had significant improvements on CDSS. Treatment group differences were not statistically significant (P = 0.493, mixed-effects model repeated measures; P = 0.497, LOCF). For 24 weeks, olanzapine-treated patients showed significantly greater improvements in depressive symptoms (results varied by depression measure and statistical approach) and GAF (P < 0.017, LOCF). A significantly higher proportion of olanzapine-treated patients completed the study (44.6% vs 29.7%; P = 0.003) and remained longer on medication (median, 163 vs 73 days, P < 0.001), compared with ziprasidone-treated patients. Olanzapine-treated patients experienced significantly (P < 0.05) greater increases in triglycerides, HgbA1c, and weight.\n For 24 weeks, olanzapine-treated patients had greater and more sustained participation in treatment, during which time significantly greater improvements were observed in depressive symptoms and GAF scores, along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients.", "This study compared the effects of olanzapine (OLZ) with those of quetiapine (QUE) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning. In this 6-month, multicenter, double-blind clinical trial, patients were randomized to treatment with OLZ (n = 171, 10-20 mg/d) or QUE (n = 175, 300-700 mg/d). Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans. The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms. Secondary measures assessed changes in functioning, psychopathology, and treatment tolerability. Treatment with OLZ or QUE led to a significant reduction in negative symptoms, with no between-group difference (P = 0.09). Both treatment groups also showed significant improvement on most efficacy measures. Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale, Quality of Life Instrumental Role domain, and level of effort in psychosocial or occupational rehabilitation programs. Significantly more OLZ-treated patients completed the study (52.6% OLZ, 37.7% QUE, P = 0.007). Treatment differences in safety were relatively small and not thought to be clinically relevant. Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE. Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy.", "This article compares the efficacy of olanzapine and risperidone for positive and negative symptoms using an 18-week, randomized, double-blind, crossover design. The hypotheses were that olanzapine would be more efficacious for treating negative symptoms, and that risperidone would be superior in treating positive symptoms. Positive and negative symptoms scores improved throughout treatment, regardless of medication type. Differences between the medications were found for negative and general psychopathology rating scales. Overall, olanzapine led to greater improvements in negative symptoms than did risperidone. When each scale was analyzed individually, greater improvements were found for olanzapine on Positive and Negative Symptoms Scale (PANSS) General,PANSS total, and Scale for the Assessment of Negative Symptoms (SANS)attention. A nearly significant trend favoring olanzapine was found for the Calgary Depression Scale. Several negative symptom subscales followed a nonsignificant trend toward olanzapine being more efficacious than risperidone.Thus, there was a very consistent pattern of greater efficacy for olanzapine, particularly for negative symptoms. Despite the small number of subjects, this study shows the potential of a within-subject design to elucidate differences in efficacy.", "The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder.\n In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period).\n Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain.\n The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.", "Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain.\n The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002.\n Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups.\n Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine.", "While the usefulness of atypical antipsychotics for improving cognitive function has been proven, the specific effects of these drugs are still unknown. The objective of this study was to investigate changes of the immediate memory and verbal working memory in patients with chronic schizophrenia after switching to one of four atypical antipsychotic agents and cessation of anticholinergic therapy. The subjects included 77 schizophrenic patients who were treated primarily with typical antipsychotics. Treatment was randomly switched to one of four atypical antipsychotics (olanzapine, perospirone, quetiapine, or risperidone) over a 4-week period, and then the drug was continued for another 4 weeks while the patient was taken off anticholinergics. The immediate memory, verbal working memory, and symptoms were evaluated. Significant improvement of immediate memory was only seen with olanzapine and risperidone. Improvement was also seen after switching to perospirone, but immediate memory worsened after treatment with this anticholinergic drug was discontinued. Deterioration was seen after switching to quetiapine, but immediate memory improved and reached the previous level after treatment with anticholinergic drugs was discontinued. Significant improvement of the verbal working memory was only seen during risperidone administration. The findings suggested that switching chronic schizophrenic patients to atypical antipsychotics can improve both the immediate memory and the verbal working memory when risperidone is used, while improvement of immediate memory can be expected with olanzapine. From the viewpoint of improving the memory, quetiapine should not be administered concomitantly with anticholinergic drugs, and caution should be exercised when discontinuing anticholinergic drugs during treatment with perospirone.", "The efficacy and safety of olanzapine were compared with those of ziprasidone.\n This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight.\n The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level.\n Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile.", "This pilot study was undertaken to estimate the acute antipsychotic effect size and side effect propensity of risperidone and olanzapine in the pediatric population, in comparison to haloperidol, a conventional antipsychotic with established efficacy. Risperidone and olanzapine are widely used as first-line treatments to ameliorate psychotic symptoms in youth, but their abilities to specifically treat children and adolescents presenting due to psychotic symptoms have not been rigorously studied. Subjects, selected because of prominent positive psychotic symptoms, were randomly assigned to double-blind, parallel treatment with risperidone, olanzapine, or haloperidol for 8 weeks. The primary outcome was reduction in the Brief Psychiatric Rating Scale for Children total score from baseline to termination. An exploratory, descriptive analysis was done to compare the three treatments. A total of 50 patients, 8-19 years, participated. All treatments reduced symptoms significantly with p-values (corrected for multiple comparisons) of 0.0018 for each of the atypical agents and 0.012 for haloperidol. In all, 88% of subjects treated with olanzapine, 74% treated with risperidone, and 53% treated with haloperidol met response criteria. The primary side effects observed in all patients were mild to moderate sedation, extrapyramidal symptoms, and weight gain. Risperidone and olanzapine acutely reduced psychotic symptoms in this pediatric sample. Exploratory comparisons indicate the magnitude of the antipsychotic response with these atypical agents is comparable to that observed with haloperidol. However, youth treated with risperidone and olanzapine experienced weight gain and extrapyramidal effects that appear more prevalent and severe than reported in adults.", "Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637 mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16 mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (> or =7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia.\n Copyright 2006 John Wiley & Sons, Ltd.", "The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders.\n One hundred twelve subjects (70% male; mean age=23.3 years [SD = 5.1]) with first-episode schizophrenia (75%), schizophreniform disorder (17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2.5-20 mg/day) or risperidone (1-6 mg/day).\n Response rates did not significantly differ between olanzapine (43.7%, 95% CI=28.8%-58.6%) and risperidone (54.3%, 95% CI=39.9%-68.7%). Among those responding to treatment, more subjects in the olanzapine group (40.9%, 95% CI=16.8%-65.0%) than in the risperidone group (18.9%, 95% CI=0%-39.2%) had subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications. Extrapyramidal symptom severity scores were 1.4 (95% CI=1.2-1.6) with risperidone and 1.2 (95% CI=1.0-1.4) with olanzapine. Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was 17.3% (95% CI=14.2%-20.5%) with olanzapine and 11.3% (95% CI=8.4%-14.3%) with risperidone. Body mass index at baseline and at 4 months was 24.3 (95% CI=22.8-25.7) versus 28.2 (95% CI=26.7-29.7) with olanzapine and 23.9 (95% CI=22.5-25.3) versus 26.7 (95% CI=25.2-28.2) with risperidone.\n Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.", "This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness.\n Patients were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) administered in twice-daily doses. Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks (primary outcome measure) based on a prespecified noninferiority margin of 20%.\n A total of 400 patients were randomly assigned to treatment with olanzapine (N=133), quetiapine (N=134), or risperidone (N=133). The mean modal prescribed daily doses were 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone. At week 52, all-cause treatment discontinuation rates were 68.4%, 70.9%, and 71.4% for olanzapine, quetiapine, and risperidone, respectively. Reductions in total score on the Positive and Negative Syndrome Scale (PANSS) were similar for the three treatment groups, but reductions in PANSS positive subscale scores were greater in the olanzapine group (at 12 weeks and at 52 weeks or withdrawal from study) and the risperidone group (at 12 weeks). The most common elicited adverse events for olanzapine were drowsiness (53%), weight gain (51%), and insomnia (38%); for quetiapine, drowsiness (58%), increased sleep hours (42%), and weight gain (40%); and for risperidone, drowsiness (50%), menstrual irregularities in women (47%), and weight gain (41%).\n Olanzapine, quetiapine, and risperidone demonstrated comparable effectiveness in early-psychosis patients, as indicated by similar rates of all-cause treatment discontinuation.", "The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge. Clozapine has been one treatment option; however, it is not universally effective and is limited in its use by safety concerns. With the introduction of newer agents, their performance relative to clozapine is of great clinical interest.\n The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients. The study was primarily designed to demonstrate the \"noninferiority\" of olanzapine compared to clozapine after 18 weeks of double-blind treatment. Conclusions were based on the one-sided lower 95% confidence limit about the treatment effect observed from the primary efficacy variable (Positive and Negative Syndrome Scale [PANSS] Total).\n Mean changes from baseline to end point in PANSS Total score, using a last observation carried forward technique, showed that both agents were comparably effective in neuroleptic resistant patients, i.e., demonstrated the \"noninferiority\" of olanzapine when compared to clozapine. Overall, significantly fewer olanzapine-treated patients (4%) discontinued for an adverse event than their clozapine-treated (14%) counterparts (p =.022). Among spontaneously reported adverse events, increased salivation, constipation, dizziness, and nausea were reported significantly more often among clozapine-treated patients, whereas only dry mouth was reported more often among olanzapine-treated patients.\n Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinically eligible for treatment with clozapine.", "Clozapine has been the gold standard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities. This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia. The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication. This 18-week, randomized, double-blind, parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At the 18-week endpoint, no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used: Positive and Negative Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or Clinical Global Impression severity (CGI-S). Response rates based on the criteria of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly different between olanzapine-treated (57.9%) and clozapine-treated patients (60.8%). There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography, and no clinically and statistically significant changes were seen in vital signs or laboratory measures in either group. Both treatments were well tolerated. Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy (treatment resistance) or intolerable side effects (treatment intolerance). Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia.", "When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.\n Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).\n Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.\n For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects." ]

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[ "A cognitive/behavioral group intervention for weight loss in patients treated with atypical antipsychotics.", "Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: a double-blind, placebo-controlled study.", "FAILURE OF DEXTROAMPHETAMINE SULFATE TO INFLUENCE EATING AND SLEEPING PATTERNS IN OBESE SCHIZOPHRENIC PATIENTS: CLINICAL AND PHARMACOLOGICAL SIGNIFICANCE.", "The effect of famotidine addition on olanzapine-induced weight gain in first-episode schizophrenia patients: a double-blind placebo-controlled pilot study.", "Phenylpropanolamine appears not to promote weight loss in patients with schizophrenia who have gained weight during clozapine treatment.", "Nizatidine for the treatment of patients with quetiapine-induced weight gain.", "Treatment of weight gain with fluoxetine in olanzapine-treated schizophrenic outpatients.", "Olanzapine-induced weight gain in patients with first-episode schizophrenia: a double-blind, placebo-controlled study of fluoxetine addition.", "A double-blind, placebo-controlled trial of sibutramine for olanzapine-associated weight gain.", "Topiramate as an adjuvant treatment with atypical antipsychotics in schizophrenic patients experiencing weight gain.", "Double-blind, placebo-controlled investigation of amantadine for weight loss in subjects who gained weight with olanzapine.", "Nutritional intervention to prevent weight gain in patients commenced on olanzapine: a randomized controlled trial.", "Adjunctive fluvoxamine inhibits clozapine-related weight gain and metabolic disturbances.", "Effects of behavioral therapy on weight loss in overweight and obese patients with schizophrenia or schizoaffective disorder.", "A 12-week, randomized, open-label, parallel-group trial of topiramate in limiting weight gain during olanzapine treatment in patients with schizophrenia.", "Nizatidine treatment and its relationship with leptin levels in patients with olanzapine-induced weight gain.", "Nizatidine for prevention of weight gain with olanzapine: a double-blind placebo-controlled trial.", "A clinical trial of the efficacy and acceptability of D-fenfluramine in the treatment of neuroleptic-induced obesity.", "The effects of an educational intervention on antipsychotic-induced weight gain.", "Metformin for prevention of weight gain and insulin resistance with olanzapine: a double-blind placebo-controlled trial.", "Amantadine for weight gain associated with olanzapine treatment." ]

[ "Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents. The prevalence of obesity, insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population. Risk reduction studies for persons with obesity, diabetes, and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction. In the landmark multi-center randomized-controlled trial study, the Diabetes Prevention Project (DPP), a cognitive/behavioral intervention, was more successful in producing weight loss and preventing diabetes than the drugs metformin, troglitazone or placebo. This pilot study examined the effectiveness of a cognitive/behavioral group intervention, modified after the DPP program, in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system. Outcome measures included body weight, body mass index, waist-hip ratios, and fasting glucose levels. Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33. The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group. The CB group participants lost an average of 5.4 lb or 2.9% of body weight, and those in the control group lost 1.3 lb or 0.6% body weight. The range of weight loss for the treatment group was from 1 to 20 lb. This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder.", "Since increased norepinephrine availability may account for the weight-reducing effect of appetite suppressants, the authors hypothesized that the addition of the selective norepinephrine reuptake inhibitor reboxetine may prevent or attenuate olanzapine-induced weight gain.\n Twenty-six patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in the study. In addition to 6 weeks of treatment with olanzapine, 10 mg/day, patients were randomly allocated in a double-blind design to receive either reboxetine, 4 mg/day, (N=13) or placebo (N=13).\n Ten patients in each group completed the 6-week trial. Patients given olanzapine and reboxetine demonstrated a significantly lower increase in body weight (mean=2.5 kg, SD=2.7) than those given olanzapine and placebo (mean=5.5 kg, SD=3.1). Significantly fewer patients in the olanzapine/reboxetine group (N=2 of 10) than in the olanzapine/placebo group (N=7 of 10) gained at least 7% of their initial weight, the cutoff for clinically significant weight gain. The addition of reboxetine to olanzapine treatment was safe and well tolerated by the patients. A between-group difference in the reduction of Hamilton depression scale scores was seen that favored the olanzapine/reboxetine group (mean difference=-3.1, SD=1.25).\n The selective norepinephrine reuptake inhibitor reboxetine may reduce olanzapine-induced weight gain in schizophrenia patients, and activation of the adrenergic system may attenuate weight gain induced by atypical antipsychotic agents.", "nan", "Olanzapine treatment is associated with substantial weight gain. In this double-blind placebo-controlled study we evaluated whether the H2 antagonist famotidine may prevent/attenuate olanzapine-induced weight gain. Fourteen first-episode DSM-IV schizophrenia patients were randomly allocated to receive either famotidine (40 mg/day, n=7) or placebo (n=7) in addition to olanzapine (10 mg/day) for 6 weeks. All patients completed the trial. Patients in both groups showed a similar increase in body weight (olanzapine/famotidine: 4.8 (3.2) kg and olanzapine/placebo: 4.9 (1.6) kg, respectively; a between-group difference of 0.14 (1.3) kg). Four of seven (57.1%) patients in the olanzapine/famotidine group and three of seven (42.9%) in the olanzapine/placebo group gained at least 7% of their initial body weight, a cut-off for clinically significant weight gain. Famotidine addition was safe and well tolerated and did not interfere with olanzapine's therapeutic effect. In conclusion, famotidine (40 mg/day for 6 weeks) is not effective in preventing/attenuating weight gain in olanzapine-treated first-episode schizophrenia patients.", "Weight gain is a common side effect of clozapine treatment and may expose patients to obesity-associated health risks. We proposed that concomitant treatment with an appetite suppressant such as phenylpropanolamine (PPA) would lead to a decrease in appetite and therefore loss of weight.\n This was a 12-week, double-blind, randomized, placebo-controlled trial of PPA, 75 mg/day, in outpatients with treatment-refractory schizophrenia (DSM-IV) who were stable on clozapine treatment for at least 4 months and had gained > 10% of their baseline body weight since starting clozapine. Patients were evaluated for adverse effects and weighed weekly. A Positive and Negative Syndrome Scale (PANSS) assessment, a short dietary quiz, and blood indices were completed monthly.\n Sixteen patients were equally randomly assigned to receive PPA or placebo. The groups did not differ in mean age, baseline weight, dose of clozapine, baseline PANSS scores, or the percent of weight gained since the start of clozapine. There was no significant effect of treatment on weight (t = 0.219, df = 10, p = .831). There was no significant change in either the total PANSS scores (t = -0.755, df = 10, p = .468), the positive or negative symptom cluster scores, or any of the remaining variables.\n Phenylpropanolamine 75 mg/day was well tolerated but was not effective in reversing established weight gain associated with clozapine treatment in stable outpatients with schizophrenia.", "It has been reported that nizatidine may reduce weight gain in schizophrenic patients on olanzapine treatment. Leptin has been reported to be associated with antipsychotic-induced weight gain. Thus, the purpose of the study was to evaluate whether nizatidine might be useful for the treatment of quetiapine-induced weight gain. Among the patients on the quetiapine monotherapy, 47 participated in the study for the two and half months of the open-label screening period. However, 28 patients who gained considerable weight in this period entered the 8-week, double-blind and placebo-controlled phase. These patients were randomly divided into two groups; quetiapine plus nizatidine (group I) and quetiapine plus placebo (group II) for the 8-week double-blind phase. The patients were evaluated at the baseline and at week 8 with respect to the positive and negative syndrome scale, body mass index, weight and serum leptin levels. The mean weight and leptin levels exhibited modest increases in both groups for the open-label screening period. In the double-blind period, in group I, a minimal, but not statistically significant, decrease in weight was observed, with a mean of 1.0 +/- 0.6 kg. The weight increased in group II. The leptin levels decreased by a mean of 0.6 +/- 0.6 ng/ml in group I, and increased by 1.0 +/- 0.9 ng/ml in group II. At evaluation at week 8, a trend toward statistical significance in the mean serum leptin levels between groups was detected. The results suggest that nizatidine treatment may stop but not reduce the weight gain and is correlated with leptin levels in patients with schizophrenia on quetiapine treatment.\n Copyright 2003 John Wiley & Sons, Ltd.", "Significant weight gain is a side effect associated with olanzapine treatment in some patients. We investigated the efficacy of high-dose fluoxetine as a weight-reducing agent for patients who develop early weight gain with olanzapine treatment. Patients that gained >/=3% of their baseline weight in the initial 8 weeks of olanzapine treatment (n=31) were randomized to double-blind treatment with placebo or fluoxetine (60 mg/day). Clinical, weight, and weight-related measures were assessed. Fluoxetine failed to demonstrate weight-reducing effects (fluoxetine group: baseline mean 80.5 kg, SD=19.1, last mean=83.5 kg, SD=19.8; placebo group: baseline mean=77.1 kg, SD=12.1, last mean=78.8 kg, SD=10.6; F=1.3; df=1, 18; p=0.3). There were no differential effects in psychopathology, extrapyramidal side effects or weight-related measures between the placebo and fluoxetine groups. Serotonin reuptake inhibitors are probably not a practical option to counteract weight gain induced by atypical antipsychotics. Atypical-induced weight gain may result from mechanisms other than 5HT reuptake blockade.", "Since olanzapine-induced weight gain may be attributable to the antagonistic activity of olanzapine at the serotonin-2C receptor, the authors hypothesized that it might be attenuated by addition of the selective serotonin reuptake inhibitor fluoxetine.\n First-episode hospitalized schizophrenia patients (N=30) were randomly assigned in an 8-week double-blind study of olanzapine, 10 mg/day, coadministered with either fluoxetine, 20 mg/day (N=15), or placebo (N=15).\n The group receiving olanzapine plus fluoxetine showed significantly less improvement in positive and disorganized symptom dimensions than the group receiving olanzapine plus placebo. The two groups demonstrated similar and substantial gradual weight gains.\n These results suggest that fluoxetine coadministration is clinically ineffective and cannot attenuate olanzapine-induced weight gain.", "Weight gain is commonly observed with olanzapine treatment and can increase the risk for obesity, cardiovascular disease, hypertension, and diabetes mellitus. This study examined the effectiveness of sibutramine, an approved weight loss agent, in overweight and obese subjects taking olanzapine for schizophrenia or schizoaffective disorder.\n Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, had been taking a stable dose of olanzapine for at least 4 months, and had a body mass index of >/=30 kg/m(2) or >/=27 kg/m(2) plus at least one cardiovascular risk factor. In a 12-week double-blind, randomized, placebo-controlled study, 37 subjects received placebo or sibutramine (up to 15 mg/day). For the first 8 weeks all subjects participated in weekly group sessions focused on nutrition and behavioral modification.\n The sibutramine and placebo groups had no significant baseline differences on age, gender, education, ethnicity, diagnosis, weight, body mass index, and blood pressure. At week 12 the sibutramine group had significantly greater losses than the placebo group in weight (mean=8.3 lb, SD=2.4, versus mean=1.8 lb, SD=1.6), waist circumference, body mass index, and hemoglobin A(1c). There were no significant differences on most side effects, although the sibutramine group exhibited a mean increase in systolic blood pressure of 2.1 mm Hg (SD=8.5), and anticholinergic side effects and sleep disturbances were at least twice as common in the sibutramine group.\n Sibutramine was an effective and well-tolerated adjunct to behavior modification for weight loss in patients with schizophrenia and schizoaffective disorder being treated with olanzapine.", "Schizophrenic patients commonly suffer weight gain, which is often associated with widely prescribed antipsychotic medicines. It is distressing to most patients who experience it and may affect their response to treatment of schizophrenia. Weight gain is also associated with treatment noncompliance and several medical conditions. This study explored the efficacy and tolerability of topiramate as an adjuvant treatment of patients with schizophrenia who were carrying excess weight. In this 12-week, randomized, placebo-controlled prospective study, 66 hospitalized patients with schizophrenia who were carrying excess weight were given topiramate at doses of 100 mg/day or 200 mg/day, or a placebo. The primary measures made were body weight, body mass index, waist measurement, hip measurement, and waist-to-hip ratio. Safety measures included physical examinations and the monitoring of adverse effects, clinical laboratory data, and vital signs. The Clinical Global Impression-Severity of Illness scale (CGI-S) and the Brief Psychiatric Rating Scale (BPRS) were used to quantify changes in schizophrenic symptoms and signs. In the 200-mg/day topiramate group, body weight, body mass index, waist measurement, and hip measurement decreased significantly compared with the 100-mg/day topiramate and placebo groups over 12 weeks. However, the waist-to-hip ratio did not change in any group. Scores on the CGI-S and BPRS decreased significantly over the 12-week period in both topiramate groups, but the decrease was not clinically meaningful. These results suggest that a higher dose of topiramate is efficacious as an adjuvant treatment of patients with schizophrenia experiencing excess weight gain. Further clinical research is required to establish guidelines for the use of topiramate as an antiobesity agent in schizophrenic patients.", "This study sought to determine if amantadine affects weight gain in psychiatric patients taking olanzapine.\n Twenty-one adults who had gained at least 5 lb with olanzapine were randomly assigned to receive amantadine (N=12) or placebo (N=9) in addition to olanzapine. The length of time taking olanzapine ranged from 1 to 44 months. Body mass index, psychiatric status, and fasting blood levels were assessed at baseline and 12 weeks.\n Significantly fewer subjects taking amantadine gained weight, with a mean change in body mass index of -0.07 kg/m2 for the amantadine group and 1.24 kg/m2 for the placebo group. This effect remained significant when the authors controlled for baseline body mass index and length of olanzapine treatment. No changes in fasting glucose, insulin, leptin, prolactin, and lipid levels were seen. Positive and Negative Syndrome Scale scores remained stable.\n Amantadine induced weight stabilization in subjects taking olanzapine and was well tolerated.", "Olanzapine is the most commonly prescribed atypical antipsychotic medication in Australia. Research reports an average weight gain of between 4.5 and 7 kg in the 3 months following its commencement. Trying to minimize this weight gain in a population with an already high prevalence of obesity, mortality and morbidity is of clinical and social importance. This randomized controlled trial investigated the impact of individual nutrition education provided by a dietitian on weight gain in the 3 and 6 months following the commencement of olanzapine.\n Fifty-one individuals (29 females, 22 males) who had started on olanzapine in the previous 3 months (mean length of 27 days +/- 20) were recruited through Peninsula Health Psychiatric Services and were randomly assigned to either the intervention (n = 29) or the control group (n = 22). Individuals in the intervention group received six 1 hour nutrition education sessions over a 3-month period. Weight, waist circumference, body mass index (BMI) and qualitative measures of exercise levels, quality of life, health and body image were collected at baseline at 3 and 6 months.\n After 3 months, the control group had gained significantly more weight than the treatment group (6.0 kg vs 2.0 kg, p < or = 0.002). Weight gain of more than 7% of initial weight occurred in 64% of the control group compared to 13% of the treatment group. The control group's BMI increased significantly more than the treatment group's (2 kg/m(2)vs 0.7 kg/m(2), p < or = 0.03). The treatment group reported significantly greater improvements in moderate exercise levels, quality of life, health and body image compared to the controls. At 6 months, the control group continued to show significantly more weight gain since baseline than the treatment group (9.9 kg vs 2.0 kg, p < or = 0.013) and consequently had significantly greater increases in BMI (3.2 kg/m(2)vs 0.8 kg/m(2), p < or = 0.017).\n Individual nutritional intervention provided by a dietitian is highly successful at preventing olanzapine-induced weight gain.", "Adjunctive fluvoxamine inhibits clozapine metabolism and decreases plasma norclozapine (a toxic metabolite of clozapine) to clozapine ratios. This study aimed to demonstrate the effects of fluvoxamine on clozapine-related weight gain, hyperglycemia, and lipid abnormalities.\n Sixty-eight treatment-resistant inpatients with a DSM-IV diagnosis of schizophrenia were randomly assigned to 2 treatment groups for 12 weeks. The monotherapy group (N = 34) received clozapine (< or = 600 mg/day). The coadministration group (N = 34) received fluvoxamine (50 mg/day) plus low-dose clozapine (< or = 250 mg/day). The study was conducted from August 1999 to October 2002.\n The 2 groups were similar in demographic data; baseline body weight and body mass index (BMI); baseline serum glucose, triglyceride, and cholesterol levels; and steady-state plasma clozapine concentration. The monotherapy patients (but not the coadministration patients) had significantly higher (p < .05) body weight, BMI, and serum glucose and triglyceride levels after treatment than at baseline. At week 12, the monotherapy patients also had significantly higher glucose (p = .035), triglyceride (p = .041), and norclozapine (p = .009) (and numerically higher cholesterol) levels than the cotreatment patients. The changes in weight and serum glucose and triglyceride levels were significantly correlated (p = .026, p = .005, and p = .028, respectively) with the plasma concentration of norclozapine but not with plasma levels of clozapine.\n These results suggest that fluvoxamine cotreatment can attenuate weight gain and metabolic disturbances in clozapine-treated patients. Plasma levels of norclozapine, but not clozapine, are associated with increases in weight and serum glucose and triglyceride levels. Of note, coadministration of fluvoxamine could increase plasma clozapine levels markedly and carry the risk of adverse events. If this combined treatment is applied, conservative introduction with reduced clozapine dosage and careful therapeutic drug monitoring of clozapine concentration is recommended.", "Obesity is common in persons with schizophrenia. Besides its adverse health effects, obesity reduces quality of life and contributes to the social stigma of schizophrenia.\n This 14-week, multicenter, open-label, rater-blinded, randomized study evaluated the effects of a group-based behavioral treatment (BT) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone. Participants were randomly assigned to receive BT or usual clinical care (UC). BT included 20 sessions during which patients were taught to reduce caloric intake. In UC, patients were encouraged to lose weight but received no special advice about weight reduction. The primary outcome measure was change in body weight.\n Seventy-two patients were enrolled. The mean +/- SD weight loss at endpoint was significant in both groups (p < .05) and numerically greater in patients receiving BT than in those receiving UC (-2.0 +/- 3.79 and -1.1 +/- 3.11 kg, respectively). More patients in the BT group than in the UC group had lost > or = 5% of their body weight at endpoint (26.5% [9/34] and 10.8% [4/37], respectively; p = .082). A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost > or = 5% of their body weight at endpoint (32.1% [9/28] vs. 10.8% [4/37], respectively, p = .038) and at week 14 (complete population; 40.9% [9/22] and 14.3% [4/28], respectively, p = .027).\n BT may be an effective method for weight reduction in patients with chronic psychotic illness.", "nan", "It has been reported that nizatidine may reduce the weight gain in schizophrenic patients receiving olanzapine treatment. Previous studies have demonstrated a relation between olanzapine-induced weight gain and serum leptin levels. Therefore, in the present study, it was planned to investigate the efficacy of nizatidine on the treatment of olanzapine-induced weight gain, and if available, whether leptin levels were associated with reductions in weight gain. Of the patients with schizophrenia on olanzapine treatment, 59 who gave informed consent entered a 3 month open-label screening period. Of them, 35 patients (59%) showed weight gain in excess of 2.5 kg. These patients were randomly divided into two groups; olanzapine plus nizatidine (group I) and olanzapine plus placebo (group II) for an 8-week double-blind phase. The patients were evaluated at the baseline and at week 8 with respect to the positive and negative syndrome scale, body mass index, weight and serum leptin levels. In the open-label period, olanzapine led to a considerable marked increase in weight and in serum leptin levels. There was no statistically significant difference between the groups with respect to weight at the beginning of the 8-week double-blind treatment period. Throughout the 8 week double-blind period, in group I, the weight decreased by 4.5 +/- 2.2 kg ( p<0.05). In contrast, weight increased in group II by a mean of 2.3 +/- 0.9 kg ( p>0.05). The leptin levels decreased by 4.4 +/- 2.3 ng/ml in group I ( p<0.01), and increased by 1.8 +/- 0.6 ng/ml in group II ( p>0.05). These changes were accompanied by changes in the leptin levels in both groups I and II. It is concluded that leptin seems to be strongly associated with olanzapine-induced weight gain and that nizatidine treatment may reduce the weight gain and the correlated leptin levels in patients with schizophrenia on olanzapine treatment.\n Copyright 2003 John Wiley & Sons, Ltd.", "Weight gain is associated with treatment with olanzapine and other psychotropic agents. Nizatidine, a histamine H-2 receptor antagonist, has been proposed to have weight-reducing effects. This double-blind trial evaluated the efficacy of nizatidine in limiting weight gain in patients with schizophrenia and related disorders who were treated with olanzapine for up to 16 weeks. After an initial screening period, 175 patients were randomized to receive olanzapine (5-20 mg) with either placebo or nizatidine (150 mg b.i.d. or 300 mg b.i.d.). Significantly less weight gain was observed on average at weeks 3 and 4 with olanzapine+nizatidine 300 mg b.i.d. (P<0.05) compared to olanzapine+placebo, but the difference was not statistically significant at 16 weeks. Nizatidine was well-tolerated and did not adversely affect clinical outcomes. Nizatidine 300 mg b.i.d. may have an early transient effect in limiting the weight gain, but this potential early effect appeared to be diminished or eliminated by 16 weeks.", "Twenty-nine overweight schizophrenic patients maintained on depot neuroleptic injections who wished to lose weight took part in a double-blind, placebo-controlled trial of 30 mg D-fenfluramine. All subjects received dietary advice. Sixteen patients completed the 12-week trial. Rate of weight loss was significantly greater in those taking D-fenfluramine. Side-effects were reported, but no deterioration in mental state was noted.", "To assess the effect of an educational intervention on antipsychotic-induced weight gain among patients with schizophrenia.\n Quasi-experimental. Seventy patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder entered this 6-month study condicted in the United States. All participants began receiving olanzapine treatment when they entered the study. The patients were then randomly assigned to an intervention group or a standard care group. Over the next 4-months, the intervention group participated in weekly psychoeducation classes focused on nutrition, exercise, and living a healthy lifestyle. Patients were followed for an additional 2 months to assess weight change.\n A statistically significant difference in weight change between the two groups was observed post-treatment and at endpoint. At endpoint, the mean weight change of the intervention group was -.06 pounds, while the mean weight change in the standard care group was 9.57 pounds. In both groups, men gained significantly more weight than did women.\n The results indicate that a structured educational intervention might have a positive effect on antipsychotic-induced weight gain among patients with schizophrenia.", "To assess whether metformin prevents body weight gain (BWG) and metabolic dysfunction in patients with schizophrenia who are treated with olanzapine.\n Forty patients taking olanzapine (10 mg daily) were randomly allocated to a metformin (n = 20; 850 to 1700 mg daily) or placebo (n = 20) group in a 14-week double-blind study. Waist circumference (WC), BWG, body mass index (BMI) fasting glucose, insulin, and lipids were evaluated at baseline and at Weeks 7 and 14 of treatment.\n At Week 14, BWG (kg) was similar in the metformin group (5.5 kg) and the placebo group (6.3 kg), P = 0.4. There were no differences between the changes in BMI, WC, glucose, insulin, insulin resistance index (HOMA-IR), and plasma lipid levels observed in the treatment group and the placebo group; however, glucose levels decreased significantly after metformin administration (P = 0.02). The HOMA-IR decreased significantly in both groups, but 3 subjects from the placebo group developed fasting glucose levels greater than 5 mmol/L. After taking metformin, triglyceride levels increased, but the cholesterol profile improved significantly.\n Metformin did not prevent olanzapine-induced BWG. While some lipid parameters worsened during placebo, the HOMA-IR improved in both the placebo and the metformin groups. Carbohydrate metabolism impairment was not systematically observed during short-term olanzapine administration.", "Patients with schizophrenia (Sch), schizoaffective, schizophreniform, or bipolar (BP) I disorders [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)]; not manic or acutely psychotic [Brief Psychiatric Rating Scale (BPRS) total score < or =45]; treated with olanzapine for 1-24 months; and who had gained > or =5% of their initial body weight were examined to determine whether amantadine could attenuate weight gain or promote weight loss. Olanzapine (Olz; 5-20 mg/day) was co-administered with double-blind treatment of 100-300 mg/day amantadine (Olz+Amt, n=60) or placebo (Olz+Plc, n=65). Visit-wise analysis of weight showed that weight change from baseline [last-observation-carried-forward (LOCF)] in the Olz+Amt group was significantly different from the Olz+Plc group at weeks 8 (P=0.042), 12 (P=0.029), and 16 (primary endpoint, mean+/-S.D.: -0.19+/-4.58 versus 1.28+/-4.26 kg, P=0.045). Mean BPRS total score, positive subscale, and anxiety-depression scores improved comparably in both groups, and Montgomery-Asberg Depression Rating Scale (MADRS) total score improved in the Olz+Amt group. Overall, amantadine was safe, was well tolerated, and attenuated weight gain or promoted weight loss in some patients who had gained weight during olanzapine therapy." ]

[ "4156898", "4153184" ]

[ "A controlled trial of clothiapine and chlorpromazine in acute schizophrenic syndromes.", "[Comparative study of clothiapine and trifluoperazine in acute episodes of paranoid schizophrenia]." ]

[ "nan", "nan" ]

[ "12771841", "14521290", "8086015", "2590331", "9825390", "11988719", "8711700", "8241852", "9237315", "15220883", "15911666", "16766370" ]

[ "Prospective randomized surgical treatments for calcifying tendinopathy.", "Open versus arthroscopic subacromial decompression: a prospective, randomized study of 34 patients followed for 8 years.", "Open vs. arthroscopic acromioplasty: a prospective, randomized study.", "Arthroscopic subacromial decompression versus open acromioplasty.", "The subacromial impingement syndrome. A study of results of treatment with special emphasis on predictive factors and pain-generating mechanisms.", "Arthroscopic versus open acromioplasty: a prospective, randomized, blinded study.", "[Acromion resection for shoulder impingement syndrome. Results after an open and a percutaneous surgical method].", "Arthroscopic surgery compared with supervised exercises in patients with rotator cuff disease (stage II impingement syndrome)", "Open versus arthroscopic subacromial decompression: analysis of one-year results.", "Arthroscopic rotator cuff repair with and without arthroscopic subacromial decompression: a prospective, randomized study of one-year outcomes.", "The effect of suture materials and techniques on the outcome of repair of the rotator cuff: a prospective, randomised study.", "Exercises may be as efficient as subacromial decompression in patients with subacromial stage II impingement: 4-8-years' follow-up in a prospective, randomized study." ]

[ "Thirty-eight patients with chronic calcifying tendinopathy of the shoulder were randomized prospectively into two groups: 19 patients had endoscopic decompression and 19 had open decompression. Thirty-three patients (19 with open and 14 with endoscopic decompression) were available for followup. Clinical and ultrasonographic investigations were done at followup. The purpose of the current study was to evaluate prospectively the clinical and sonographic results after open decompression and after endoscopic decompression. Apportionment of age and gender was similar in both groups. The followup was 15.7 months for patients after open decompression and 17.1 months for patients after endoscopic decompression. The average Patte score was 84.5 points (84.4 for patients who had endoscopic decompression and 84.6 for patients who had open decompression). Corresponding results were found with a Constant and Murley score of 96.6 points (97.6 for patients who had endoscopic decompression and 95.8 for patients who had open decompression). In the endoscopic group physiotherapy was recommended for 5 weeks more than in the open surgery group. Similar results were seen for the incapacity to work in both groups with 4.6 weeks for the patients who had endoscopic surgery and 5 weeks for the patients who had open surgery. No nerve injuries, wound infections, or other postoperative complications were found. Comparison of both surgical methods showed good clinical and score results. Endoscopic and open surgery are equally effective in the treatment of chronic calcifying tendinopathy.", "In a randomized prospective study, we selected 15 patients for arthroscopic subacromial decompression (ASD) and 19 patients for open subacromial decompression (OSD). All had impingement syndrome (Neer grade II), and had been unsuccessfully treated without surgery for more than 6 months. The UCLA Shoulder Rating Scale, Visual Analogue Scales for pain and satisfaction, isokinetic dynamometer recordings and physical testing were assessed preoperatively and at 1 (except isokinetic testing), 3, 6, and 12 months, and, finally, 8 years after surgery. We found essentially no differences in the clinical tests between the groups during this period. The use of ASD or OSD seems to be a matter of cosmesis and personal preference.", "Between May 1988 and May 1990, 44 patients with Stage II impingement were randomized into open and arthroscopic treatment groups. Forty-one patients were available for final follow-up in May 1991: 22 in the open group, 19 in the arthroscopic group. Comparisons of pain, function, motion, and strength were made preoperatively and at 2, 6, 12, 26, and 52 weeks postoperatively. Final analysis showed that the main benefits of arthroscopic acromioplasty were evident in the first 3 months postoperatively. Arthroscopic patients regained flexion and strength more rapidly than did open patients, had shorter hospitalizations, used less narcotics, and returned more quickly to both work and activities of daily living. By 3 months postoperatively, open patients tended to \"catch up\" with arthroscopic patients, and further recovery was equivalent. In both groups, full recovery took at least 1 year for the majority of patients and in both groups at 1 year > 90% of patients achieved a satisfactory result. Because of its medical and economic advantages for both the patient and the health-care system, we conclude that arthroscopic acromioplasty should become the procedure of choice for patients with impingement syndrome refractory to conservative treatment.", "A random prospective comparison was conducted of 20 patients who underwent arthroscopic subacromial decompression or open acromioplasty as treatment for impingement syndrome. The Neer anterior acromioplasty served as comparison in the evaluation to arthroscopic technique. The comparison shows more rapid rehabilitation and better range of motion in the arthroscopic group. Time of surgery is also shorter for arthroscopy than for the open technique. Arthroscopic subacromial decompression appears to be superior to open acromioplasty as a treatment for impingement syndrome.", "Forty-two patients with subacromial impingement syndrome entered a randomized prospective study comparing open anterior acromioplasty with a physiotherapy regime. The criterion for a successful outcome of treatment was a reduction of the initial pain score of more than 50% using the visual analogue scale (VAS) technique. The evaluation was performed by an independent observer. At the 6-month follow-up, treatment in the surgical group had been successful in 12/21 (57%) patients versus 6/18 (33%) in the physiotherapy group. A one-year evaluation revealed 16/21 (76%) \"successes\" in the surgical group. A direct and unbiased comparison with the physiotherapy group was not possible at one year, since 13 patients chose surgery after initial physiotherapy. However, in \"an intention to treat\" analysis outcome at one year was significantly better in those randomized to surgery. We found two standardized, composite, active movements--the \"Pour out of a Pot\" manoeuvre requiring the emptying of a pot of water, and the \"Hand in Neck\" manoeuvre--to be of predictive value for the outcome of surgery. When combining three pain-related variables into a criterion for prediction of success, a sensitivity of 78% (p < 0.02) and a specificity of 90% (p < 0.03) were attained. We advance the hypothesis that pain in the impingement syndrome is mainly elicited by comparison of the subacromial bursa. In some patients a traction-responsive pain generator in the supraspinatus tendon may be present as well.", "The purpose of this study is to determine whether arthroscopic acromioplasty is equivalent or superior to open acromioplasty, in a prospective, randomized, controlled, blinded clinical trial. Seventy-one patients with a clinical diagnosis of impingement syndrome were randomized to arthroscopic or open acromioplasty. Nine were excluded because of full-thickness rotator cuff tears diagnosed after randomization. Sixty-two patients (49 men and 13 women) with a minimum follow-up of 12 months (mean, 25 months) were included. The patient groups were virtually identical with regard to duration of symptoms, shoulder functional demands, age, sex, hand dominance, mechanism of onset, range of motion, strength, joint laxity, and the presence of a compensation claim. Patients were prospectively randomized to arthroscopic or open acromioplasty after stratification for age (>50 years),associated ligamentous laxity, and the presence of an ongoing compensation claim. The main outcome measure was visual analog scales for pain and function. Also recorded were UCLA shoulder scores and visual analog scales for postoperative improvement, patient satisfaction, and a variety of clinical measures. An independent blinded examiner assessed all patients. There was no significant difference between open and arthroscopic acromioplasty in visual analog scales for postoperative improvement (P =.30), patient satisfaction (P =.94), UCLA shoulder score (P =.69), or strength (P =.62); however, open was superior to arthroscopic acromioplasty for pain and function (P =.01). Overall, 67% of patients had a good or excellent result. This increased to 87% when unsettled compensation claims were excluded. Repeat (open) acromioplasty was performed in 5 patients in the unsuccessful arthroscopic group without improvement. Open acromioplasty was equivalent to arthroscopic acromioplasty for UCLA scores and patient satisfaction. For pain and function, both gave significant improvement but the open technique may be superior. Unsettled compensation is a predictor of poor outcome.", "Anterior acromioplasty as described by Neer has been an effective procedure for shoulder impingement syndrome. Artroscopic acromioplasty is regarded as a technically demanding procedure. Since 1988 we have developed a closed percutaneous acromioplasty using motorized instruments. The purpose of this randomised clinical trial was to compare the results of open and closed percutaneous acromioplasty. We found a significant improvement in shoulder score, but no differences between the group treated with the open procedure and the group treated with the closed procedure.", "To compare the effectiveness of arthroscopic surgery, a supervised exercise regimen, and placebo soft laser treatment in patients with rotator cuff disease (stage II impingement syndrome).\n Randomised clinical trial.\n Hospital departments of orthopaedics and of physical medicine and rehabilitation.\n 125 patients aged 18-66 who had had rotator cuff disease for at least three months and whose condition was resistant to treatment.\n Arthroscopic subacromial decompression performed by two experienced surgeons; exercise regimen over three to six months supervised by one experienced physiotherapist; or 12 sessions of detuned soft laser treatment over six weeks.\n Change in the overall Neer shoulder score (pain during previous week and blinded evaluation of function and range of movement by one clinician) after six months.\n No differences were found between the three groups in duration of sick leave and daily intake of analgesics. After six months the difference in improvement in overall Neer score between surgery and supervised exercises was 4.0 (95% confidence interval -2 to 11) and 2.0 (-1.4 to 5.4) after adjustment for sex. The condition improved significantly compared with placebo in both groups given the active treatments. Treatment costs were higher for those given surgery (720 pounds v 390 pounds).\n Surgery or a supervised exercise regimen significantly, and equally, improved rotator cuff disease compared with placebo.", "The results of open subacromial decompression (OSD) were compared with arthroscopic subacromial decompression (ASD) after 1 year in 32 subjects (4 bilateral), and the correlation between the two shoulder rating scales for impingement was documented. Patients were evaluated clinically on the modified University of California at Los Angeles (UCLA) shoulder rating scale, and Constant scale. Scapular position and rotation were evaluated as well as a rotation and abduction shoulder strength test using the Cybex II dynamometer. No parameters revealed significant differences between the groups, except for the UCLA score which indicated an advantage for the ASD group (p = 0.046). The OSD group scored 24.5 (5.45) on the UCLA scale and 73.8 (18.9) on the Constant scale, whereas the ASD group scored 28.3 (5.6) and 80.8 (16.4). To study the correlation between both scales, the Pearson correlation product-moment coefficient was calculated and a high correlation (r = 0.81) obtained. Less mobility was found in the operated arm for all parameters, with the exception of glenohumeral abduction in both groups and passive elevation in the OSD group. Only in the OSD group did the scapula in the operated extremity show more abduction of the inferior angle of the scapula. Weaker abduction strength in the operated side was found in the ASD group, whereas in the OSD group there was significantly less adduction and external rotation strength at 180 degrees/s en 240 degrees/s. We conclude that after one year the open group tends to catch up with the arthroscopic patients and that the main benefits after arthroscopic surgery as described in literature are more evident in the shorter period.", "We performed a prospective, randomized study to determine whether arthroscopic subacromial decompression changes the outcome of rotator cuff repair. We performed a power analysis to ensure statistical validity. Patients scheduled for arthroscopic rotator cuff repair were randomized to cuff repair with arthroscopic subacromial decompression (group 1) or without it (group 2). All other aspects of the surgical and postsurgical treatment were identical. We included patients with full-thickness tears limited to the supraspinatus tendon and a type 2 acromion. We excluded patients with prior surgery, those with larger tears involving two or more tendons, those with a type 1 or 3 acromion, those with workers' compensation claims, and those who had concomitant procedures (labral repair, acromioclavicular joint resection) There were 47 patients in group 1 and 46 in group 2. Minimum follow-up was 1 year (mean, 15.6 +/- 3.3 months). We recorded the American Shoulder and Elbow Surgeons (ASES) shoulder scores preoperatively and postoperatively. There was no statistical difference in postoperative ASES scores between group 1 (91.5 +/- 10.3) and group 2 (89.2 +/- 15.1) (P =.392). The change in ASES score over time did not differ between the two groups (61.1 vs 60.2, P =.363). In conclusion, within the parameters described above, arthroscopic subacromial decompression does not appear to change the functional outcome after arthroscopic repair of the rotator cuff.", "In a prospective, randomised study on the repair of tears of the rotator cuff we compared the clinical results of two suture techniques for which different suture materials were used. We prospectively randomised 100 patients with tears of the rotator cuff into two groups. Group 1 had transosseous repair with No. 3 Ethibond using modified Mason-Allen sutures and group 2 had transosseous repair with 1.0 mm polydioxanone cord using modified Kessler sutures. After 24 to 30 months the patients were evaluated clinically using the Constant score and by ultrasonography. Of the 100 patients, 92 completed the study. No significant statistical difference was seen between the two groups: Constant score, 91% vs 92%; rate of further tear, 18% vs 22%; and revision, 4% vs 4%. In cases of further tear the outcome in group 2 did not differ from that for the intact repairs (91% vs 91%), but in group 1 it was significantly worse (94% vs 77%, p = 0.005). Overall, seven patients had complications which required revision surgery, in four for pain (two in each group) and in three for infection (two in group 1 and one in group 2).", "To compare the prognosis of subacromial impingement (SAI) stage II treated conservatively or with subacromial decompression.\n A follow-up study after 4-8 years in a randomized controlled trial (RCT) with 90 adult cases with SAI treated in a Danish hospital from 1996 to 2000 with graded physiotherapy and exercises or arthroscopic subacromial decompression. Outcomes were proportion of time per year with income transfers (indexed 0-1), including total transfers (marginalization), sick leave and disability pension obtained from the registry at the Ministry of Work. Self-reported function, working capability, employment status and global improvement were obtained by questionnaire in September 2004. The main outcomes are given as differences in development from baseline.\n Seventy-nine (88%) responded to the questionnaire and registry data were obtained from 81. After 1 year the marginalization index increased by 0.45 [95% confidence interval (CI) 0.35-0.56] for surgery and 0.25 (0.16-0.34) for physiotherapy. Cases undergoing surgery also tended to have more sick payments during the first year, but the difference was not significant. Four years after inclusion, changes in indices did not differ between treatment groups. Self-reported outcomes after 4-8 years did not differ between treatment groups.\n The results of surgical decompression were equal to those of conservative treatment, and the surgery group had more income transferrals during the first year of follow-up." ]

[ "19650848" ]

[ "Effect of improved home ventilation on asthma control and house dust mite allergen levels." ]

[ "The warm, humid environment in modern homes favours the dust mite population, but the effect of improved home ventilation on asthma control has not been established. We tested the hypothesis that a domestic mechanical heat recovery ventilation system (MHRV), in addition to allergen avoidance measures, can improve asthma control by attenuating re-colonization rates.\n We conducted a randomized double-blind placebo-controlled parallel group trial of the installation of MHRV activated in half the homes of 120 adults with asthma, allergic to Dermatophagoides pteronyssinus. All homes had carpets steam cleaned and new bedding and mattress covers at baseline. The primary outcome was morning peak expiratory flow (PEF) at 12 months.\n At 12 months, the primary end-point; change in mean morning PEF as compared with baseline, did not differ between the MHRV group and the control group (mean difference 13.5 l/min, 95% CI: -2.6 to 29.8, P = 0.10). However, a secondary end-point; evening mean PEF, was significantly improved in the MHRV group (mean difference 24.5 l/min, 95% CI: 8.9-40.1, P = 0.002). Indoor relative humidity was reduced in MHRV homes, but there was no difference between the groups in Der p 1 levels, compared with baseline.\n The addition of MHRV to house dust mite eradication strategies did not achieve a reduction in mite allergen levels, but did improve evening PEF." ]

[ "10356376", "17036474" ]

[ "The effect of acupuncture in chronic intractable epilepsy.", "[Clinical observation on catgut implantation at acupoint for treatment of general paroxysmal epilepsy]." ]

[ "We examined the effect of acupuncture on epileptic seizures in humans in a controlled clinical setting. Treatment was administered by two Chinese professors of acupuncture. Effect was measured by change in seizure frequency. Twenty-nine patients with chronic intractable epilepsy completed the study. They were randomized in two groups; 15 were given classical acupuncture and 14 were given sham acupuncture. There was a reduction in seizure frequency in both groups, which did not reach a level of statistical significance. There was also an increase in the number of seizure-free weeks in both groups, which reached a level of significance in the sham group. Thus, we have not been able to prove a beneficial effect of acupuncture in chronic intractable epilepsy.\n Copyright 1999 BEA Trading Ltd.", "To search for an effective method for treatment of general paroxysmal epilepsy.\n One hundred cases were randomly divided into a treatment group of 50 cases treated with catgut implantation at Dazhui (GV 14), Jinsuo (GV 8), Fenglong (ST 40), etc., and a control group of 50 cases treated with oral administration of sodium valproate.\n The scores for epilepsy after treatment significantly improved in the both groups (P<0.05); the total effective rate was 94.0% in the treatment group and 82.0% in the control group with a significant difference between the two groups (P<0.05).\n Catgut implantation at acupoint has a definite therapeutic effect on general paroxysmal epilepsy with no adverse effect." ]

[ "11130603", "8700092", "3754633", "8278239", "3634818", "8254063", "3347763", "7398449", "1001842" ]

[ "Physiologic and behavioral effects of gentle human touch on preterm infants.", "Effects of gentle human touch on preterm infants: pilot study results.", "Tactile/kinesthetic stimulation effects on preterm neonates.", "Patterns of physiologic and behavioral response of intermediate care preterm infants to intervention.", "Multimodal stimulation of the premature infant.", "Massage effects on cocaine-exposed preterm neonates.", "Maternally administered tactile, auditory, visual, and vestibular stimulation: relationship to later interactions between mothers and premature infants.", "Effects of prematurity and early intervention on responsivity to tactual stimuli: a comparison of preterm and full-term infants.", "The effects of tactile and kinesthetic stimulation on neonatal development in the premature infant." ]

[ "The purpose of this study was to evaluate the effects of a gentle human touch (GHT) intervention provided to 42 preterm infants (27-33 weeks gestational age), for 10 min, three times daily for 10 days. There was no significant difference in mean HR levels or in percent of abnormal heart rate (HR) or O2 saturation comparing 10-min baseline (B), GHT, and 10-min post-touch (PT) phases. There were significantly lower levels of active sleep, motor activity, and behavioral distress during GHT compared to B and P phases. There were no differences among the 42 infants in the GHT group and 42 infants in a randomly assigned control group on any outcome variable including weight gain, morbidity status, or behavioral organization. The findings suggest that GHT generally is a safe and soothing type of touch to provide to young preterm infants, but that individual infant responses to touch need to be continuously monitored by NICU staff and parents.", "A pilot study was conducted to evaluate the effects of gentle human touch (GHT) provided for 15 minutes a day to preterm infants from day 7 to day 12 of life. The study suggested that GHT has no adverse effects on the oxygen saturation or heart rate levels of small preterm infants and that GHT has a soothing effect as evidenced by decreased levels of active sleep, motor activity, and behavioral distress. These results can provide NICU nurses with a basis for guiding parents in their early interactions with preterm infants in the NICU.", "Tactile/kinesthetic stimulation was given to 20 preterm neonates (mean gestational age, 31 weeks; mean birth weight, 1,280 g; mean time in neonatal intensive care unit, 20 days) during transitional (\"grower\") nursery care, and their growth, sleep-wake behavior, and Brazelton scale performance was compared with a group of 20 control neonates. The tactile/kinesthetic stimulation consisted of body stroking and passive movements of the limbs for three, 15-minute periods per day for a 10 days. The stimulated neonates averaged a 47% greater weight gain per day (mean 25 g v 17 g), were more active and alert during sleep/wake behavior observations, and showed more mature habituation, orientation, motor, and range of state behavior on the Brazelton scale than control infants. Finally, their hospital stay was 6 days shorter, yielding a cost savings of approximately $3,000 per infant. These data suggest that tactile/kinesthetic stimulation may be a cost effective way of facilitating growth and behavioral organization even in very small preterm neonates.", "To determine the safety of a developmental intervention for use with preterm infants and feasibility of a time sampling procedure.\n An experimental design was used to test an intervention with clinically stable 33-34-week postconceptional age infants over a 4-day period. Repeated outcome measures included pulse rate, oxygen saturation levels, and infant behavioral state.\n The intervention resulted in significant differences in infant behavioral state with the experimental group achieving more alertness. Physiologic parameters remained within normal limits both during and after the intervention.\n The protocol was found to be safe for implementation with clinically stable preterm infants. Behavioral state findings suggest the potential for the intervention to promote alertness. Results suggest that changes in oxygen saturation and pulse rate were dependent upon changes in behavioral state.", "nan", "Thirty preterm cocaine-exposed preterm neonates (mean gestational age 30 wks, mean birth weight = 1212 g, mean intensive care unit duration = 18 days) were randomly assigned to a massage therapy or a control group as soon as they were considered medically stable. Group assignment was based on a random stratification of gestational age, birth weight, intensive care unit duration, and entry weight into the study. The treatment group (N = 15) received massages for three 15-minute periods 3 consecutive hours for a 10-day period. Findings suggested that the massaged infants (1) averaged 28% greater weight gain per day (33 vs 26 g) although the groups did not differ in intake (calories or volume), (2) showed significantly fewer postnatal complications and stress behaviors than did control infants, and (3) demonstrated more mature motor behaviors on the Brazelton examination at the end of the 10-day study period.", "Thirty-three mother-infant pairs were randomly assigned to one of three groups: control, talking, or interactive (RISS). The later treatment included massage, talking, eye contact and rocking. The intervention (RISS) was administered to determine whether mothers and their preterm infants who actively interacted with each other would differ on later maternal and infant behaviors. The talking and RISS treatments were administered at specified time intervals 24 hours after delivery. Prior to hospital discharge, mother-infant interaction was assessed during a feeding. Significant differences were identified among the three groups for maternal (p less than .03) and infant (p less than .05) behaviors. These results suggest that active maternal interaction with the premature infant may enhance specific components of mother-infant interaction.", "Cardiac and behavioral responses to a tactual stimulus were evaluated during the first sleep cycle for 3 groups of infants: 30 full terms, 30 nonintervened preterms, and 30 intervened preterms. Prior to testing, the latter group had received a regimen of multimodal sensory stimulation, which emphasized the tactual and vestibular modalities. The results showed that the intervention altered the preterms' sensory functioning mainly during active sleep. In this state, the full terms and the intervened preterms exhibited a significant cardiac acceleration to the stimulus, while the nonintervened preterms failed to do so. Similarly, the behavioral response of the intervened preterm more closely approximated that of the full terms. During quiet sleep the intervention did not affect either the cardiac or the behavioral response. In this sleep state, the full terms' cardiac response was that of monophasic acceleration, whereas both groups of preterms exhibited a biphasic response with a smaller initial acceleration which was followed by a deceleration below baseline. Behaviorally, the preterms responded less frequently and gave smaller responses than the full terms. Thus there were marked differences between preterms and full terms, and the intervention seemed to narrow this gap to some extent.", "The effects of tactile and kinesthetic stimulation on the neonatal development of 12 premature infants were investigated. Experimental infants received four 15-min periods of tactile and kinesthetic stimulation daily for 10 days. The control infants received only standard, routine nursery care. Data were collected daily on 8 dependent measures: weight, number of feedings, amount of formula intake, body temperature, respiration, heart rate, frequency of voiding, and frequency of stooling. The data analyses revealed significant differences in amount of formula intake and in weight at the end of the treatment period in favor of the experimental infants. Additionally, the experimental infants required significantly fewer feedings during the stimulation period. All others dependent measures were nonsignificant." ]

[ "18592627", "11246096", "12476070", "3347522", "18086500", "17937869", "11930611", "19208045" ]

[ "Effectiveness of massage, sucrose solution, herbal tea or hydrolysed formula in the treatment of infantile colic.", "Infant massage improves mother-infant interaction for mothers with postnatal depression.", "Massage therapy by mothers enhances the adjustment of circadian rhythms to the nocturnal period in full-term infants.", "Developmental and temperament outcomes of sensory stimulation in healthy infants.", "Postnatal depression and mother and infant outcomes after infant massage.", "[Effect of infantile touching on behavior development in infants].", "[Effects of touch on growth and mentality development in normal infants].", "Salivary cortisol and behavioral state responses of healthy newborn infants to tactile-only and multisensory interventions." ]

[ "The aim of the study was to evaluate the effectiveness of massage, sucrose solution, herbal tea or hydrolysed formula, each used individually in the treatment of infantile colic.\n The term colic describes a group of symptoms that occur frequently in infants, consisting of paroxysmal abdominal pain and severe crying. Infant colic is of importance for both parents and the community health services that provide families with care, and is therefore an important clinical problem that is amenable to nursing interventions.\n This prospective and randomised-controlled study involved 175 infants in Turkey.\n Data were gathered by using Wessel criteria; parents wrote a daily structured diary, recording the onset and duration of crying. Patients were assigned randomly into four different intervention groups (massage, sucrose solution, herbal tea and hydrolysed formula) and control group. Duration of crying following each intervention was recorded in the diary by parents for a one week period.\n There was a significant reduction in crying hours per day in all intervention groups. The difference between mean duration of total crying (hours/day) before and after the intervention infants in hydrolysed formula group was found higher than massage, sucrose and herbal tea group. The difference between mean duration of total crying(hours/day) before and after the intervention infants in massage group was found lower than other intervention groups and all groups.\n Our findings demonstrated that varied interventions such as administration of massage, sucrose solution, herbal tea and hydrolysed formula are effective in the treatment of colic. The difference between mean duration of total crying (hours/day) before and after the intervention in hydrolysed formula group was found higher than other intervention groups. Hydrolysed formula was the most effective in reducing the duration of crying (hours/day) when compared with the other intervention groups. Massage intervention yielded the least symptomatic improvement among all the interventions.\n Colic treatment models used in this study can be used by nurses in neonatal and primary healthcare settings as an aid to families for the treatment of infantile colic.", "Postnatal depression can have long term adverse consequences for the mother-infant relationship and the infant's development. Improving a mother's depression per se has been found to have little impact on mother-infant interaction. The aims of this study were to determine whether attending regular massage classes could reduce maternal depression and also improve the quality of mother-infant interaction.\n Thirty-four primiparous depressed mothers, median 9 weeks postpartum, identified as being depressed following completion of the Edinburgh Postnatal Depression Scale (EPDS) at 4 weeks postpartum, were randomly allocated either to an infant massage class and a support group (massage group) or to a support group (control group). Each group attended for five weekly sessions. Changes in maternal depression and mother-infant interaction were assessed at the beginning and the end of the study by comparing EPDS scores and ratings of videotaped mother-infant interaction.\n The EPDS scores fell in both groups. Significant improvement of mother-infant interaction was seen only in the massage group.\n The sample size was small and had relatively high dropout. It was not possible to distinguish which aspects of the infant massage class contributed to the benefit.\n This study suggests that learning the practice of infant massage by mothers is an effective treatment for facilitating mother-infant interaction in mothers with postnatal depression.", "The objective of this study was to investigate the effect of massage therapy on phase adjustment of rest-activity and melatonin secretion rhythms to the nocturnal period in full-term infants. Rest-activity cycles of infants (measurement 1, n = 16) were measured by actigraphy before and after 14 days of massage therapy (starting at age 10 [+/-4] d) and subsequently at 6 and 8 weeks of age. 6-Sulphatoxymelatonin excretion was assessed in urine samples at 6, 8, and 12 weeks of age (measurement 2, n = 21). At 8 weeks the controls revealed one peak of activity at approximately 12 midnight (11 p.m.-3 a.m.) and another one at approximately 12 noon (11 a.m.-3 p.m.), whereas in the treated group, a major peak was early in the morning (3 a.m.-7 a.m.) and a secondary peak in the late afternoon (3 p.m.-7 p.m.). At 12 weeks, nocturnal 6-sulphatoxymelatonin excretions were significantly higher in the treated infants (1346.38 +/- 209.40 microg/night vs 823.25 +/- 121.25 microg/night, respectively; <.05). It is concluded that massage therapy by mothers in the perinatal period serves as a strong time cue, enhancing coordination of the developing circadian system with environmental cues.", "Eighty-one healthy, full-term infants were randomly assigned to a control group or one of three experimental conditions: daily administration of a cephalocaudal stroking procedure; placement on a multisensory hammock that provided auditory, vestibular, and tactile stimulation during expected sleep cycles; and a combination of the prior two treatments. All interventions were given during the first 3 months of life. Infants in the control group received the natural stimulation provided in their home environments without additional supplementation. Four- and 8-month assessments were done using the Bayley Scales of Infant Development and the Revised Infant Temperament Questionnaire. There were no significant treatment effects on weight or psychomotor development. Although infants receiving unimodal stimulation obtained lower 8-month cognitive development scores than infants in other experimental and control groups, their scores were within normal range. Control group infants achieved the most optimum mood and distractibility scores at both 4 and 8 months.", "Postnatal depression can be a long lasting condition which affects both the mother and her baby. A pilot study indicated that attending baby massage improved maternal depression and mother-infant interactions. The current study further investigates any benefits of baby massage for mothers with postnatal depression and their infants.\n Mothers scoring (3)13 on the Edinburgh Postnatal Depression Scale (EPDS) at 4 weeks postpartum were randomly assigned to attend baby massage classes (n=31) or a support group (n=31). They completed depression, anxiety and Infant Characteristics Questionnaires and were filmed interacting with their infants before and after 6 intervention sessions, and at one year. Thirty four non-depressed mothers also completed the study.\n More of the massage than support group mothers showed a clinical reduction in EPDS scores between four weeks and outcome (p<0.05). At one year, massage-group mothers had non-depressed levels of sensitivity of interaction with their babies, whereas the support group did not. There were no other differences in either mother or child between the two intervention groups. Depressed mothers did not achieve control depression or anxiety scores at one year.\n For ethical reasons, the study did not include a control group of depressed mothers who did not receive an intervention.\n Both intervention groups showed reductions in depression scores across the study period, but the massage group did better on some indices. They also had somewhat better interactions with their infants at one year, but these effects were limited.", "nan", "To determine the effects of conducting Touch to infants upon their growth and mental development, sleeping and disease conditions, as well as the difference of effects of conducting Touch among infants of different month age.\n 310 normal full-term infants aged 0-6 months were divided randomly into Touch group (n = 208) and control group (n = 102). Parents of Touch group were asked to conduct Touch to their infants 2-3 times/day, lasting 15-20 minutes every time, for at least 3 months. Intelligence tests were performed to infants of both groups at the beginning of the experiment and 6 months later (CDCC measurement table was employed). Data such as height, weight, circumferences of head and chest, sleeping, feeding and disease conditions etc. were recorded each month in a successive period of 6 months. Statistical analysis was conducted using SPSS 10.0.\n (1) The average score of mental development (MDI) was 7.4 higher, with a statistically significant difference, among the infants who began to receive touch within 3 months after birth than those infants with the same age in control group. The average score of psychomotor development index (PDI) was 5.8 higher, with a statistically significant difference, among the infants who began to receive touch within 3 months after birth than those infants with the same age in control group. Infants who began to receive touch within 3 months after birth slept remarkably better than those in control group did. No significant difference was found in scores of MDI and PDI and sleeping condition between infants who began to receive touch 3 months after birth and the infants with the same age in the control group. (2) Weight gain and growth in chest circumference in infants receiving touch within one month after birth were significantly better compared with the infants of the same age in the control group. There was no significant difference in values of height and head circumference between the two groups. There was no significant difference in values of height and head circumference between the two groups. (3) No significant difference in the incidence rates of acute respiratory infection and diarrhea disease was found between the touch group and control group.\n (1) Growth and mental development of infants can be improved by touch. Tthe earlier to conduct touch the better the effects. (2) Touch helps improve sleeping condition in infants.", "To compare changes in stress reactivity (measured via the biomarker salivary cortisol) and behavioral state in healthy newborn infants immediately following 1 of 2 interventions: (1) tactile-only stimulation or (2) a multisensory, auditory, tactile, visual, and vestibular stimulation with a control group.\n A randomized prospective design pilot study.\n Normal newborn nurseries of 2 midwestern perinatal centers.\n Forty healthy newborn infants receiving standard nursing care.\n Infants were randomly assigned to receive 15 minutes of tactile-only, auditory, tactile, visual, and vestibular, or no stimulation 30 minutes before feeding. Saliva samples were collected before, immediately following, and 10 minutes postintervention. Behavioral state was judged every minute.\n Tactile-only group infants had the largest increase in cortisol levels, followed by control group infants. In contrast, infants who received the multisensory intervention showed a significant steady decline in cortisol. Asleep was the predominant state for all 3 groups and cry was minimal.\n Tactile-only stimulation may increase infant stress reactivity while the benefit of the multisensory auditory, tactile, visual, and vestibular intervention may be in the reduction of infant stress reactivity. Interventions appeared to have minimal effect on stress reactivity based on behavioral state." ]

[ "15737951", "11171733", "10950800", "9806037", "12576938" ]

[ "A randomized, placebo-controlled study of the use of filgrastim in non neutropenic patients with nosocomial pneumonia.", "Filgrastim in patients with pneumonia and severe sepsis or septic shock.", "A randomized controlled trial of filgrastim for the treatment of hospitalized patients with multilobar pneumonia.", "A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia. CAP Study Group.", "Multicenter, double-blind, placebo-controlled study of the use of filgrastim in patients hospitalized with pneumonia and severe sepsis." ]

[ "Pneumonia remains the number one cause of death from infectious diseases in Western Europe and the United States despite the introduction of potent broad-spectrum antibiotics. Granulocyte colony-stimulating factor is considered to improve host defense during infection and may be an effective adjunctive in the treatment of severe infections. We examined the efficacy of granulocyte colony-stimulating factor (r-metHUG-CSF, filgrastim) with regard to clinical response in non-neutropenic ICU patients with nosocomial pneumonia in a prospective, randomized, placebo-controlled trial. 28 patients with newly diagnosed nosocomial pneumonia were randomly assigned to receive 300-480 microg filgrastim or placebo subcutaneously for up to seven days. Study endpoints were death within 15 days, duration of antibiotic therapy and occurrence of serious adverse events (SAE). No significant differences were observed in respect of 15-day (filgrastim1/12 vs. placebo 2/16) or 30-day mortality (1/12 vs.4/16, p=0.355), and length of antibiotic treatment (13.5 vs.11.5 days, p=0.985). Sepsis developed in 1/12 patients in the filgrastim and 6/16 patients in the placebo group (p=0.184). None of the patients developed ARDS or any other SAE related to the study medication. Filgrastim is safe in non-neutropenic ICU patients with nosocomial pneumonia. A benefit of filgrastim with regard to clinical endpoints could not be observed, while there was a trend toward reduced sepsis rate.", "Evaluate the safety of filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) administration, combined with standard therapy, in patients with pneumonia and either septic shock or severe sepsis who were receiving mechanical ventilation.\n Multicenter, double-blind, randomized, placebo-controlled study.\n ICU, multicenter.\n Eighteen patients with pneumonia and hypotension, or in the absence of shock, two or more end-organ dysfunctions, were enrolled and treated. Baseline acute physiology and chronic health evaluation II scores and median age for the filgrastim (n = 12) and placebo (n = 6) groups were 25.0 and 49.5 years and 31.5 and 56.5 years, respectively.\n Filgrastim (300 microg) or placebo was administered IV daily for up to 5 days. Measurements and results: Study end points included safety; biological response, including endogenous cytokine levels, endotoxin levels, and neutrophil counts; and mortality. Cytokine and endotoxin levels were highly variable in both groups. By day 29, 3 of 12 filgrastim-treated patients and 4 of 6 placebo-treated patients had died. There were no differences in types and occurrences of adverse events, including ARDS, or in outcome between the two groups. Three of four placebo-treated patients had persistent bacterial growth on bronchoscopy repeated after 48 h compared with 2 of 10 filgrastim-treated patients.\n Filgrastim appeared to be well tolerated in this population of patients with pneumonia and severe sepsis or septic shock. Larger studies to determine the benefit of filgrastim in patients with pneumonia and sepsis or organ dysfunction are warranted.", "This study assessed the safety and efficacy of filgrastim (r-metHuG-CSF [recombinant human methionine granulocyte colony-stimulating factor]), when combined with intravenous (IV) antibiotics, in the treatment of hospitalized adult patients with multilobar community-acquired pneumonia (CAP). Four hundred eighty patients were randomized to receive placebo (n=243) or filgrastim 300 microg/day (n=237), in addition to standard therapy. Treatment with study drug was continued for 10 days, until the peak white blood cell (WBC) count reached 75x109/L, until discharge from the hospital, until death, or until IV antibiotics were discontinued. Study-related observations continued through day 29. Filgrastim increased WBC counts (baseline median, 13.3x109/L; median peak, 43. 8x109/L). The 2 treatment groups were not statistically different with respect to the study end points; however, there was a trend toward reduction of mortality in patients with pneumococcal bacteremia. Although further studies will be required to validate this observation, filgrastim was safe and well tolerated when administered to patients with multilobar CAP.", "Because of the critical role of neutrophils in host defenses, it was hypothesized that stimulation of neutrophil production and function with Filgrastim would improve the outcome of hospitalized patients with community-acquired pneumonia. To test this hypothesis, a randomized, placebo-controlled, multicenter trial of Filgrastim (300 micrograms/day up to 10 days) as an adjunct to antibiotics was conducted for these patients. Outcome measures included time to resolution of morbidity (TRM, a composite measure of temperature, respiratory rate, blood oxygenation, and chest radiograph), 28-day mortality, length of stay, and adverse events. Filgrastim increased blood neutrophils 3-fold, but TRM, mortality, and length of hospitalization were not affected. Treatment, however, accelerated radiologic improvement and appeared to reduce serious complications (e.g., empyema, adult respiratory distress syndrome, and disseminated intravascular coagulation). Filgrastim administration was safe and well tolerated in these patients. Additional trials are needed to establish the value of this approach to treatment of infectious diseases.", "To determine the safety and efficacy of filgrastim (r-metHuG-CSF) in combination with intravenous antibiotics to reduce the rate of mortality in patients with pneumonia and sepsis.\n This study was multicenter, double-blind, and randomized.\n Intensive care units PATIENTS Adult patients with bacterial pneumonia, either acquired or nosocomial, as confirmed by chest radiograph and positive culture or Gram-negative stain, and severe sepsis, defined as sepsis-induced hypotension or organ dysfunction.\n Standard antibiotic therapy with or without filgrastim (300 microg/day) or placebo administered as a 30-min intravenous infusion. The study drug was started within 24 hrs of enrollment and was continued for 5 days or until the white blood cell count reached >75.0 x 10(9) cells/L.\n The primary end point was the occurrence of mortality through day 29; secondary end points included occurrence of subsequent organ dysfunction, time to discharge from intensive care unit, number of days on mechanical ventilatory support, and time to death. Study-related observations were recorded through day 10 and included vital signs, onset of organ dysfunction, clinical laboratory variables, and adverse events. Filgrastim increased the white blood cell count to a median peak of 31.7 x 10(9) cells/L from a baseline of 12.3 x 10(9) cells/L. The two groups were well matched and did not differ significantly with regard to severe adverse events, time to death, occurrence of end-organ dysfunction, days of intensive care unit hospitalization, or days on mechanical ventilatory support. Mortality was low in both treatment groups; the mortality rate in patients with adult respiratory distress syndrome was similar between the two groups.\n The addition of filgrastim to the antibiotic and supportive care treatment of patients with pneumonia complicated by severe sepsis appeared to be safe, but not efficacious in reducing mortality rates or complications from this infection." ]

[ "12801736", "10768435" ]

[ "Multiple-dose activated charcoal for treatment of yellow oleander poisoning: a single-blind, randomised, placebo-controlled trial.", "Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomised controlled trial." ]

[ "Deliberate self-poisoning with yellow oleander seeds is common in Sri Lanka and is associated with severe cardiac toxicity and a mortality rate of about 10%. Specialised treatment with antidigoxin Fab fragments and temporary cardiac pacing is expensive and not widely available. Multiple-dose activated charcoal binds cardiac glycosides in the gut lumen and promotes their elimination. We aimed to assess the efficacy of multiple-dose activated charcoal in the treatment of patients with yellow-oleander poisoning.\n On admission, participants received one dose of activated charcoal and were then randomly assigned either 50 g of activated charcoal every 6 h for 3 days or sterile water as placebo. A standard treatment protocol was used in all patients. We monitored cardiac rhythm and did 12-lead electocardiographs as needed. Death was the primary endpoint, and secondary endpoints were life-threatening cardiac arrhythmias, dose of atropine used, need for cardiac pacing, admission to intensive care, and number of days in hospital. Analysis was by intention to treat.\n 201 patients received multiple-dose activated charcoal and 200 placebo. There were fewer deaths in the treatment group (five [2.5%] vs 16 [8%]; percentage difference 5.5%; 95% CI 0.6-10.3; p=0.025), and we noted difference in favour of the treatment group for all secondary endpoints, apart from number of days in hospital. The drug was safe and well tolerated.\n Multiple-dose activated charcoal is effective in reducing deaths and life-threatening cardiac arrhythmias after yellow oleander poisoning and should be considered in all patients. Use of activated charcoal could reduce the cost of treatment.", "Severe cardiac glycoside cardiotoxicity after ingestion of yellow oleander seeds is an important problem in rural areas of Sri Lanka. Currently, patients must be transferred to the capital for temporary cardiac pacing. We did a randomised controlled trial to investigate whether anti-digoxin Fab could reverse serious oleander-induced arrhythmias.\n After a preliminary dose-finding study, 66 patients who presented to hospital with a serious cardiac arrhythmia were randomised to receive either 1200 mg of anti-digoxin Fab or a saline placebo. A 12-lead electrocardiogram, 3 min rhythm strip, and blood sample for measurement of electrolytes and cardiac glycosides were taken before treatment and at 12 timepoints thereafter.\n 34 patients received anti-digoxin Fab and 32 received placebo. The presenting arrhythmia had resolved completely after 2 h in 15 antibody-treated patients and two controls (p<0.001); 24 and five patients, respectively, were in sinus rhythm at 8 h (p<0.001). Kaplan-Meier analysis of time to first reversal showed a significant response to anti-digoxin Fab. The heart rate increased in cases, from 49.1 per min at baseline to 66.8 at 2 h, but not in controls (50.6 per min at baseline to 51.5; p<0.001). Mean serum potassium concentrations decreased from 4.9 mmol/L to 4.1 mmol/L at 2 h in cases; no such decrease occurred in controls.\n Anti-digoxin Fab fragments are a safe and effective treatment for serious cardiac arrhythmias induced by yellow oleander. Their use in small rural hospitals in Sri Lanka should minimise costly transfer of patients and reduce the numbers of deaths; however, further study will be required to confirm this reduction." ]

[ "9294350", "6581053", "12831223", "2025619", "15947223", "11455377" ]

[ "A 12-month clinical comparison of resin-modified light-activated adhesives for the cementation of orthodontic molar bands.", "Comparison between a zinc phosphate cement and a glass ionomer cement for cementation of orthodontic bands.", "An in vivo and ex vivo study to evaluate the use of a glass polyphosphonate cement in orthodontic banding.", "A comparative clinical trial of a glass ionomer and a zinc phosphate cement for securing orthodontic bands.", "An investigation into the use of two polyacid-modified composite resins (compomers) and a resin-modified glass poly(alkenoate) cement used to retain orthodontic bands.", "Modified composite or conventional glass ionomer for band cementation? A comparative clinical trial." ]

[ "A clinical trial is reported on the retention rates of resin-modified light-activated adhesives for the cementation of orthodontic molar bands. Fifty consecutive cases were fully banded and monitored over 12 months. Fuji II LC (GC International) recorded a failure rate of 2.9%, Bandlok (Reliance Orthodontic Products) 8.1%, with Ketac Cem (Espe) chemical cure 3.5%. There were no statistically significant differences between these rates. Fuji II LC and Ketac Cem failed at the interface between the adhesive and the metal, while Bandlok failed at the interface between the enamel and the adhesive. It is suggested that Fuji II LC and Ketac Cem will afford greater protection to the enamel against microleakage and demineralization than Bandlok.", "nan", "The purpose of this study was to examine the effectiveness of a new glass polyphosphonate cement (Diamond) for orthodontic banding. Thirty-one subjects underwent in vivo testing to compare the failure rate of bands cemented using the test cement and bands cemented using a conventional glass polyalkenoate cement (Ketac-Cem) over a 6-month period at the beginning of active appliance therapy. In an ex vivo experiment 60 extracted teeth were banded using either the test cement or a glass polyalkenoate cement, and subjected to a debanding force using a Lloyd universal testing machine until failure. In the in vivo study the overall proportion of failure of the bands cemented with each cement was identical at 0.048. However, in the ex vivo study the probability of failure for the glass polyphosphonate cement was significantly higher than for the glass polyalkenoate cement, and the force to deband the glass polyalkenoate cement was greater than that of the glass polyphosphonate cement. In the clinical setting the new glass polyphosphonate cement performed as well as a conventional glass polyalkenoate cement, and these results suggest that it could be used as an alternative cement for orthodontic banding. The results of the ex vivo test bring into question the usefulness of this laboratory test as an indicator of clinical performance.", "This is a report of a clinical trial, comparing an experimental glass ionomer luting cement with a zinc phosphate cement for securing orthodontic bands. The comparison was made by using survival analysis techniques. The glass ionomer cement performed significantly better than the zinc phosphate cement.", "The aim of this investigation was to determine the effectiveness of a conventional glass poly(alkenoate) cement (Intact) and newer polyacid-modified composite resin cements (Transbond Plus and Ultra Band-Lok) to retain orthodontic bands. In the in vitro part of this study, stainless steel bands were cemented to 240 extracted third molar teeth in three test groups comprising Intact, Transbond Plus and Ultra Band-Lok. The force to deband (N) for all three cements was recorded using an Instron universal testing machine after the following observation periods: 20 minutes and 3, 6 and 12 months. The results indicated that all three cements increased their median force to deband after 12 months. Of the two compomers, Transbondtrade mark Plus demonstrated the highest median force to deband at all four time intervals. In the in vivo part of the study, 30 patients participated in a randomized cross-mouth clinical trial where the molar bands were cemented in place using either Intact or Transbond Plus. Ultra Band-Lok was not used in the clinical part of the study. The results showed there to be no clinically significant difference in band failure rates between the two cements. When patients were asked to score each for taste, there was a significant difference, with the glass poly(alkenoate) cement (Intact) being more acceptable than the polyacid-modified composite Transbond Plus (P < 0.001). No significant differences were observed in the in vitro median force to deband or in vivo band failure rates between the glass poly(alkenoate) cement and the polyacid-modified composite resins. The choice of cementing agent can therefore be made on patient factors, e.g. taste, or operator factors, e.g. ease of handling, cost and shelf life.", "The time to first failure, the position of band failure at deband, and the change in enamel white spot lesions of teeth bonded with a modified composite or a conventional glass ionomer were compared in a randomized half-mouth trial over the full course of orthodontic treatment. One hundred forty band pairs were cemented in 98 subjects. Overall band failure rates of 5% and 2.8% were recorded for the modified composite and the conventional glass ionomer, respectively, with no significant difference found between their times to first band failure. At the end-of-treatment deband, the position of band failure was predominantly at the enamel-cement interface for the modified composite and at the band-cement interface for the conventional glass ionomer (P <.001). A comparison of changes in mean enamel white spot lesion scores during treatment did not reveal significant differences between the cement groups (P =.16)." ]

[ "1356851", "23515202", "19664769", "19644697", "17903230", "11543749", "21880029", "18031745", "14698825" ]

[ "A randomized controlled trial of valethamate bromide in acceleration of labor.", "Effect of hyoscine butylbromide first stage of labour in multiparus women.", "Meperidine versus valethamate bromide in shortening the duration of active labor.", "A randomised controlled study comparing Drotaverine hydrochloride and Valethamate bromide in the augmentation of labour.", "The effect of hyoscine butylbromide on the first stage of labour in term pregnancies.", "Drotaverine hydrochloride vs. valethamate bromide in acceleration of labor.", "Use of an antispasmodic (rociverine) to shorten the length of labor: a randomized, placebo-controlled trial.", "Drotaverine hydrochloride versus hyoscine-N-butylbromide in augmentation of labor.", "Drotaverine hydrochloride for augmentation of labor." ]

[ "A randomized controlled study of valethamate bromide administered by intramuscular injection in acceleration of labor was done in 60 consecutive primigravidae and 60 consecutive multigravidae admitted in labor at 2-4 cm cervical dilatation. There was no difference observed in the rate of cervical dilatation between those who received valethamate bromide and those who received normal saline. However, maternal tachycardia was observed in significantly more women primigravida RR 1.97, 95% CI 1.3-3.0; multigravida RR 2.16, 95% CI 1.3-3.6) who had received valethamate bromide.", "Prolonged labor is one of the most important risk factors for perinatal compromise and, if caused by obstructed labor, it carries the risk of uterine rupture, postpartum hemorrhage (PPH), puerperal sepsis, and maternal death.\n To determine whether or not hyoscine butylbromide shortens the stages of labor, without an increase in maternal or neonatal complications.\n In single-blinded randomized clinical trial study, 188 multiparas women in active phase of labor who were admitted to Shahid Sadoughi Hospital from October 2006 to April 2007 in Yazd - Iran, were evaluated. They were divided hyoscine group (n = 94) received 20mg (1ml) of hyoscine and control group (n = 94) received 1 ml of normal saline was given as placebo, intravenously. The effects of hyoscine in shortening labor time; and neonatal Apgar score was compared.\n Duration of the first (mean± SD: 186.8 ± 125.6 minutes vs. 260.4 ± 120.9 minutes, p= 0.00 1) and second stage of labor (mean± SD: 20.0 ± 8.1minutes vs. 25.8 ± 9.4 minutes, p= 0.03) was shorter in hyoscine group. Frequency of cesarean section and mean of neonatal Apgar score at minutes of one and 5 were not different in both groups. No serious adverse events were seen in the two groups.\n Injection of hyoscine in active phase of labor can be effective in shortening of labor without any adverse effect on mother and fetus.", "To compare the efficacy and safety of meperidine hydrochloride and valethamate bromide against placebo in shortening the duration of active labor.\n We randomly assigned 160 nulliparous women with a singleton pregnancy at term who needed induction of labor to one of 3 treatments: 50 mg of meperidine (n=53), 16 mg of valethamate bromide (n=53), or a normal saline solution as placebo (n=54). All medications were given by slow intravenous infusion. Labor duration was the main outcome measure.\n The intervals between infusion and complete cervical dilation and between infusion and delivery were significantly reduced (P<0.001 and P<0.01) in the meperidine group (103.0+/-64.5 minutes and 119.8+/-70.2 minutes), in contrast to the placebo group (173.9+/-74.8 minutes and 192.2+/-82.8 minutes). However, differences were not significant between the 2 treatment groups (139.6+/-63.1 minutes and 160.6+/-71.9 minutes), or between the valethamate bromide and the placebo group.\n Meperidine, but not valethamate bromide, significantly shortened the duration of active labor in nulliparous women with a singleton pregnancy at term.", "Cervical dilatation is a poorly understood process. Various drugs have been used to facilitate this process and reduce the duration of labour and thereby reduce feto-maternal complications. The present study is an attempt to compare and evaluate the efficacy of Drotaverine hydrochloride and Valethamate bromide in the process of cervical dilatation and labour augmentation.\n A prospective randomised trial of 146 low-risk women in spontaneous labour was conducted. 49 women were given Drotaverine (Group 1), 49 women were given Valethamate (Group 2) and 48 women were given placebo (Group 3). At 4 cm of cervical dilatation, elective amniotomy was done and the injection was given intramuscularly, and repeated every hour for a maximum of three doses.\n There was a statistically significant difference in the mean injection-delivery times (time from first injection to delivery of the baby), which was 183.2 min (SD 78.8) in the Drotaverine group compared to 206.5 min (SD 69.7) in the Valethamate group, and 245 min (SD 70.9) in the control group. The mean cervical dilatation rate (cm/h) was 3 (SD 1.4), 2.4 (SD 0.9) and 1.9 (SD 0.6) in groups 1, 2 and 3, respectively, and these differences were statistically significant. There were no statistically significant differences in the duration of second and third stage of labour. Transient side effects such as foeto-maternal tachycardia, flushing of the face and dryness of mouth were noted with Valethamate. A few patients complained of headache in the Drotaverine group.\n Both Drotaverine and Valethamate appear to significantly help cervical dilatation and augment first stage of labour. But, Drotaverine is superior to Valethamate with fewer side effects.", "To determine whether hyoscine butylbromide shortens the first stage of labour, without an increase in maternal or neonatal complications.\n Randomised, double-blinded, controlled trial.\n The Antenatal clinics and Labour and Delivery ward of the University Hospital of the West Indies, Kingston, Jamaica.\n Women in spontaneous labour at term.\n Either drug or placebo was given intravenously once the women entered active labour.\n The duration of the first stage of labour. Secondary outcomes included comparisons of the duration of the second and third stages of labour, blood loss at delivery, rate of caesarean section, and APGAR scores in the neonates between the two groups.\n A total of 129 women yielded data for analysis. Of these, 69 women received the placebo and 60 received hyoscine butylbromide. The mean time for the first stage in the control group was 228 minutes, compared with 156 minutes in the drug group, representing a decrease of 31.7% (P = 0.001). There was no significant change in the duration of the second and third stages of labour, and no difference in blood loss or in APGAR scores. There was a slight (but statistically insignificant) increase in the caesarean section rate.\n Hyoscine butylbromide is effective in significantly reducing the duration of the first stage of labour, and it is not associated with any obvious adverse outcomes in mother or neonate.", "To compare the efficacy and safety of drotaverine hydrochloride and valethamate bromide in shortening the duration of labor.\n In a randomized controlled trial of 150 nulliparous women in established labor with cervical dilation of 4 cm, 50 women were given drotaverine (group I), 50 women were given valethamate (group II) and another 50 women were not given any medication (group III). Duration of labor, mode of delivery, side effects, and neonatal outcome were measured in all cases. Appropriate non-parametric tests and chi(2) tests were used for assessment of statistical significance.\n In the three groups, 100%, 96% and 46% women delivered within 6 h, respectively. The injection-to-delivery interval was significantly reduced in the drotaverine group (193.96 min) in contrast to the valethamate group (220.68 min) and control group (412.84 min). The rate of cervical dilation was highest in the drotaverine group (2.04 cm/h) compared with the valethamate bromide group (1.86 cm/h) and control group (1.01 cm/h). There were no major maternal or fetal adverse effects in any group, but minor side effects were more common in the valethamate group.\n Both intramuscular drotaverine hydrochloride and valethamate bromide are effective in acceleration of labor; however, drotaverine accelerates labor more rapidly and is associated with less side effects.", "To determine the effectiveness of rociverine, an antispasmodic drug, for reducing the duration of labor among nulliparous women managed according to a standard intrapartum protocol.\n Randomized controlled trial.\n An academic tertiary care hospital.\n Nulliparae in spontaneous active labor, with cervical dilatation between 3 and 5 cm.\n Participants were randomly assigned to receive either an intramuscular injection of 20mg rociverine (n=55) or the same volume of saline (n=56).\n Cervical dilatation rate (from administration of study drug to full dilatation).\n Laboring women who received rociverine had faster cervical dilatation than those assigned to placebo (2.43 ± 1.84 vs. 1.85 ± 1.38 cm/hour, p=0.03). The time interval from treatment administration to full cervical dilatation was shorter in the rociverine group than in the placebo group (220 ± 125 vs. 278 ± 129 min, p=0.04). No difference was found in any other obstetric outcome. No adverse effects have been recorded from rociverine administration.\n Intrapartum administration of rociverine to nulliparous women may help to reduce the duration of the first stage of labor in a context of uniform labor management.\n © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.", "To study and compare the efficacy and side effects of drotaverine hydrochloride and hyoscine-N-butylbromide in the augmentation of labor.\n A prospective randomized trial of 150 women in active labor included 50 women given drotaverine (group 1), 50 women given hyoscine-N-butylbromide (group 2), and 50 women given no medication (group 3). Duration of labor, rate of cervical dilation, mode of delivery, side effects, and neonatal outcome were compared among the groups.\n The mean duration of the active phase of labor was 4.48+/-2.26 h, 3.9+/-2.42 h, and 3.6+/-2.07 h in groups 1, 2, and 3, respectively. The mean rate of cervical dilation was 2.6 cm/h, 2.4 cm/h, and 2.5 cm/h, respectively. The differences were not statistically significant. There was no difference in the duration of the second and third stages of labor. No adverse maternal or fetal outcomes were noted.\n Drotaverine hydrochloride and hyoscine-N-butylbromide do not have a role in augmentation of labor.", "To study the use of drotaverine hydrochloride for acceleration of labor and relief of labor pains.\n In this double-blind placebo-controlled randomized study, 100 primigravidas in uncomplicated spontaneous labor at term were given drotaverine hydrochloride or placebo (distilled water) intramuscularly. Labor events, including pain (assessed by a visual analog scale and a verbal rating scale), neonatal outcome, and side effects of the drug were recorded. Student's t-test was used for analysis.\n Forty-four patients in the drug group and 40 in the placebo group had complete data for analysis after decoding. In drotaverine group, there was a mean 15% reduction in the duration of the first stage of labor and a mean 19% reduction in the second stage. The maximum shortening of the first stage (28%) was observed when drotaverine was administered when cervical dilatation was 4 cm (P=0.044). There were no adverse fetal effects, but atonic postpartum hemorrhage was more common in the drotaverine group. There was no relief of pain with the drug except in the fourth stage of labor.\n Drotaverine hydrochloride is safe and effective in accelerating labor, but not effective in lessening labor pain." ]

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[ "A pilot randomized controlled trial of a daily muscle stretch regime to prevent contractures in the arm after stroke.", "Comparing botulinum toxin A with casting for treatment of dynamic equinus in children with cerebral palsy.", "The use of knee splints after total knee replacements.", "A programme of static positional stretches does not reduce hemiplegic shoulder pain or maintain shoulder range of motion--a randomized controlled trial.", "Mobilization regimens for the prevention of jaw hypomobility in the radiated patient: a comparison of three techniques.", "Low-load, prolonged stretch in the treatment of knee flexion contractures in nursing home residents.", "The effects of casting on upper extremity motor disorders after brain injury.", "Night splinting does not increase ankle range of motion in people with Charcot-Marie-Tooth disease: a randomised, cross-over trial.", "The effect of serial casting on gait in children with cerebral palsy: preliminary results from a crossover trial.", "A randomized comparative study of two methods for controlling Tendo Achilles contracture in Duchenne muscular dystrophy.", "Splinting the hand in the functional position after brain impairment: a randomized, controlled trial.", "Effects of splinting on wrist contracture after stroke: a randomized controlled trial.", "Four weeks of daily stretch has little or no effect on wrist contracture after stroke: a randomised controlled trial.", "The effect of casting combined with stretching on passive ankle dorsiflexion in adults with traumatic head injuries.", "Passive stretching does not enhance outcomes in patients with plantarflexion contracture after cast immobilization for ankle fracture: a randomized controlled trial.", "Is routine splintage following primary total knee replacement necessary? A prospective randomised trial.", "Thirty minutes of positioning reduces the development of shoulder external rotation contracture after stroke: a randomized controlled trial.", "Effectiveness of a bed positioning program for treating older adults with knee contractures who are institutionalized.", "Physiotherapeutic treatment improves oral opening in oral submucous fibrosis.", "Twelve weeks of nightly stretch does not reduce thumb web-space contractures in people with a neurological condition: a randomised controlled trial.", "Neutral functional realignment orthosis prevents hand pain in patients with subacute stroke: a randomized trial.", "Examination of shoulder positioning after stroke: A randomised controlled pilot trial.", "Randomised trial of the effects of four weeks of daily stretch on extensibility of hamstring muscles in people with spinal cord injuries.", "The role of passive stretching in the treatment of ankylosing spondylitis.", "The role of the rehabilitation brace in restoring knee extension after anterior cruciate ligament reconstruction: a prospective controlled study.", "Effects of splinting in the treatment of hand contractures in progressive systemic sclerosis.", "Neurodevelopmental therapy and upper-extremity inhibitive casting for children with cerebral palsy.", "Orthotic intervention for development of hand function with C-6 quadriplegia.", "A randomized controlled pilot study to obtain the best estimate of the size of the effect of a thermoplastic resting splint on spasticity in the stroke-affected wrist and fingers.", "Pectoral stretching program for women undergoing radiotherapy for breast cancer.", "Does 12 weeks of regular standing prevent loss of ankle mobility and bone mineral density in people with recent spinal cord injuries?", "Contracture preventive positioning of the hemiplegic arm in subacute stroke patients: a pilot randomized controlled trial.", "Dynamic splinting after treatment with botulinum toxin type-A: a randomized controlled pilot study.", "A randomized trial assessing the effects of 4 weeks of daily stretching on ankle mobility in patients with spinal cord injuries." ]

[ "To evaluate the feasibility and effects of daily stretch positioning for prevention of contractures in stroke patients without arm function.\n Randomized controlled pilot study.\n Stroke rehabilitation ward, U.K.\n Twenty-five subjects drawn from an initial pool of 126 presenting with loss of arm function, all within four weeks of stroke.\n In addition to usual care, subjects in the experimental group (n=13) were prescribed two 30-min stretches for wrist and finger flexors and two 30-min stretches targeting shoulder adductors and internal rotators, per day for up to 12 weeks post stroke. Stretches were carried out by therapists and nursing staff.\n Passive range of wrist extension and shoulder external rotation to standard force or to pain at four, eight and twelve weeks after stroke.\n Compliance was variable. Frequency of positioning was fair from four to eight weeks post stroke but declined after that. Mean (SD) frequency of stretch positions completed between four and eight weeks was 36.5 (13.0) for the wrist, 31.2 (14.1) for the shoulder, out of 56 prescribed. There were no significant effects of treatment. By eight weeks post stroke the mean range of wrist extension and shoulder external rotation lost on the affected side in both groups was approximately 30 degrees.\n The stretch treatment was not well tolerated over many weeks. Statistical power was low due to the large degree of variability of range of motion and small sample size. The regime tested cannot be recommended as a workable treatment to prevent contractures.", "The purpose of this study was to compare the cumulative efficacy (three treatment sessions) of botulinum toxin A (BTX-A) alone, casting alone, and the combination of BTX-A and casting in the management of dynamic equinus in ambulatory children with spastic cerebral palsy (CP). Thirty-nine children with spastic CP (mean age 5y 10mo, range 3 to 9y) were enrolled in the study. A multicenter, randomized, double blind, placebo-controlled prospective study was used. Children were randomly assigned to one of three treatment groups: BTX-A only (B), placebo injection plus casting (C), or BTX-A plus casting (B+C). The dosage for the BTX-A injections was 4U/kg per extremity. Assessments were performed at baseline, 3, 6, 7.5, and 12 months with a total of three treatments administered after the evaluations at baseline, 3, and 6 months. Primary outcome measures were ankle kinematics, velocity, and stride length. Secondary outcome measures were ankle spasticity, strength, range of motion, and ankle kinetics. Group B made no significant change in any variable at any time. Groups C and B+C demonstrated significant improvements in ankle kinematics, spasticity, passive range of motion, and dorsiflexor strength. Results of this 1-year study indicate that BTX-A alone provided no improvement in the parameters measured in this study, while casting and BTX-A/casting were effective in the short- and long-term management of dynamic equinus in children with spastic CP.", "The aim of this randomised prospective study was to establish whether the use of knee splints following total knee replacement is necessary. The study included 81 patients undergoing total knee replacement who were randomised into a 'splint' and a 'no splint' group post-operatively. The following parameters were recorded: The range of movement pre-operatively, 5 days post-operatively and 6 weeks post-operatively; the length of time to straight leg raise; the blood drained from the wound; and the amount of post-operative analgesia required. We found that patients in the 'no splint' group achieved significantly greater flexion at 5 days and 6 weeks post-operatively but drained significantly more blood from the wound. Transfusion requirements were similar in the two groups. There was no other significant difference in the parameters measured between the two groups. In conclusion we found no evidence to advocate the use of knee splints following total knee arthroplasty.\n Copyright 2002 Elsevier Science B.V.", "To evaluate the effectiveness of a programme of static positional stretches and positioning of the stroke-affected shoulder for maintaining shoulder external rotation and decreasing hemiplegic shoulder pain.\n Randomized controlled trial with pretest and posttest design.\n Inpatient rehabilitation unit.\n Thirty-two participants (17 treatment, 15 comparison) with a first time stroke who were admitted for rehabilitation. Interventions: Treatment participants completed a programme of static positional stretches of the stroke-affected shoulder twice daily and positioned the stroke-affected upper limb in an armrest support at all other times when seated.\n The main outcome measures were pain-free range of motion into external rotation, pain in the stroke-affected shoulder at rest and with movement, motor recovery and functional independence.\n All participants demonstrated a significant loss of external rotation (P = 0.005) with no significant group differences. All participants demonstrated a significant improvement in motor recovery (P < 0.01) and functional independence (P < 0.01) with no significant group differences. There were no significant effects for pain. The comparison group recorded a decrease in mean pain reported with movement from admission to discharge, and the treatment group recorded an increase.\n Participation in the management programme did not result in improved outcomes. The results of this study do not support the application of the programme of static positional stretches to maintain range of motion in the shoulder. The effect of increasing pain for the treatment group requires further investigation.", "This study evaluated and compared the Therabite Jaw Motion Rehabilitation System (Therabite Corporation, Bryn Mawr, PA) to tongue blades as a technique for maintaining and/or improving mandibular range of motion in post-irradiated patients. Three groups of patients were evaluated and compared: 1) unassisted exercise, 2) mechanically assisted mandibular mobilization with stacked tongue depressors combined with unassisted exercise, and 3) the Therabite System combined with unassisted exercise. The initial average maximum incisal opening (MIO) for the study population was 21.6 mm, and did not vary significantly among the groups. Measurements were recorded at 2-week intervals for 10 weeks. At week 6 and thereafter, the net increase in MIO of group 3 (13.6 mm [+/- 1.6 mm]) was significantly greater than group 1 (6.0 mm [+/- 1.8 mm]) and group 2 (4.4 mm [+/- 2.1 mm]) (P < .05). The rate of improvement leveled after 4 week in group 1 and group 2. However, the rate of gain in MIO in the Therabite group (group 3) remained constant at 10 weeks. There was no statistical difference between groups 1 and 2.", "The purpose of this study was to do a pilot test of the effectiveness of prolonged stretch (use of splint) in reducing knee flexion contractures more than a traditional program of passive range of motion (PROM) in a group of nursing home residents.\n The subjects were 28 nursing home residents with 10 degrees or more of knee flexion contracture bilaterally. Eighteen subjects completed the study.\n Data were collected prior to the initiation of the intervention and at monthly intervals during the 6 months of treatment. Repeated measurements were made of hip, knee, and ankle range of motion (ROM); the torque required to maintain passive impairment. knee extension; knee pain; several indicators of function; and cognitive impairment. Both legs of each subject received PROM and manual stretching twice a week; in addition, one leg was given a prolonged stretch (use of a splint) five times a week.\n There were no differences in knee ROM between the side that received prolonged stretching and the side that received only PROM and manual stretching at the beginning of the study. No differences in ROM or torque measurements existed between the side that received prolonged stretching and the side that received only PROM and manual stretching at any interval, nor in ROM or torque over time for either side. Because of the low statistical power of the study, the results should be viewed with caution.\n Physical therapists need to question whether prolonged stretch for nursing home residents with knee flexion contractures greater than 10 degrees is of any greater benefit than PROM and manual stretching. Investigations of other treatment protocols and treatment doses are needed, including work in the area of prevention of knee flexion contractures. For the pilot group of nursing home residents studied, gains in knee extension did not occur with the use of prolonged stretch for 3 hours a day, 5 days per week. [Steffen TM, Mollinger LA. Low-load, prolonged stretch in the treatment of knee flexion contractures in nursing home residents.", "This study compares casting to traditional techniques, such as passive range of motion, static stretch, and splinting, in the treatment of the hypertonic upper extremity in individuals with severe brain injury.\n Fifteen subjects with brain injury were randomly assigned to one of two groups. One group received a month of casting followed by a month of traditional therapy; the second group received 1 month of traditional therapy followed by casting. The subjects' limbs were evaluated for range of motion, clinical indications of spasticity, and functional use of the extremity at three intervals--before intervention, after the first month of intervention, and after the second month of intervention. Two sample t-tests and paired t-tests were used in data analysis.\n All but one subject showed a greater improvement in range of motion with casting than with traditional treatment; 11 subjects showed a greater improvement in clinical measures of spasticity with casting. There was no apparent correlation between these measures and functional use of the extremity.\n These findings suggest that casting is more effective than traditional techniques in reducing contracture and in decreasing hypertonicity in some cases. The greater improvements in these motor indicators with casting did not translate into greater gains in functional use of the upper extremities.", "What is the effect of wearing splints at night to stretch the plantarflexors on dorsiflexion range of motion (ROM) in people with Charcot-Marie-Tooth disease?\n Randomised, assessor-blinded, cross-over trial.\n 14 people (1 dropout) aged 7 to 30 years with Charcot-Marie-Tooth disease Type 1A and with < or = 15 degrees dorsiflexion range of motion (ROM).\n A splint holding the ankle in maximum dorsiflexion was worn nightly on one leg for 6 weeks followed by the opposite leg for the subsequent 6 weeks.\n The primary outcome was dorsiflexion ROM; secondary outcomes were eversion ROM, and dorsiflexion, eversion, and inversion strength, measured before and after splinting, and three months later.\n There was no significant difference between the experimental and the control intervention in terms of ROM or strength. Wearing the splint at night increased dorsiflexion ROM by 1 degree (95% CI -3 to 4; p = 0.72) and eversion ROM by 1 degree (95% CI -1 to 3; p = 0.28) compared to not wearing the splint. Wearing the splint increased dorsiflexion strength by 41 N (95% CI -53 to 135; p = 0.38), reduced eversion strength by 6 N (95% CI -112 to 101; p = 0.92) and reduced inversion strength by 8 N (95% CI -110 to 95; p = 0.88) compared to not wearing the splint.\n Wearing night splints does not increase ankle ROM or strength in people with Charcot-Marie-Tooth disease Type 1A.", "Serial casting aims to improve an equinus gait pattern in children with spastic cerebral palsy (SCP). We evaluated the effect of short-term stretch casting on gait in children with SCP, compared to the natural history. A crossover trial, consisting of a control phase and a casting phase, was conducted with children randomised into two groups. Both groups were assessed clinically, and using 3D gait analysis, at 0, 5 and 12 weeks. Subjects in one group had the 3 month casting phase first and in the other had the 3 month control period first. Casts were changed weekly and set at maximum available ankle dorsiflexion. The mean changes at 5 weeks and 12 weeks from baseline measurements in the casting phase were compared with the change within the same time interval in the control phase. Significant improvements in passive ankle dorsiflexion (knee flexed) were found at 5 and 12 weeks. Passive ankle dorsiflexion (knee extended), ankle dorsiflexion in single support, ankle dorsiflexion in swing and minimum hip flexion in stance improved significantly at 5 weeks but not at 12 weeks from baseline. Other kinematic parameters, the score on the Gillette Functional Assessment Questionnaire, and maximum reported walking distance were not changed by casting. Casting to improve range appears to improve passive and dynamic ankle dorsiflexion, but the changes are small, short lived and do not appear to affect function.", "A 30-month prospective randomized study of 27 Scandinavian boys with confirmed diagnosis of Duchenne muscular dystrophy was done to compare the effect of passive stretching combined with the use of night splints (group A) or passive stretching (group B) on the evolution of Tendo Achilles contractures. Assessments were based on the methodology of Scott et al. (Muscle Nerve 1982;5:291-301)Analysis of the pattern and mechanism of dropout was done to eliminate bias between the two groups. Logistic regression showed that Tendo Achilles contracture was the most important variable (P=0.0020) for dropout. Methods of statistical analysis for longitudinal data avoiding induced serial correlations were used in the analysis. The expected annual change in Tendo Achilles contracture was found to be 23% less in group A than in group B after equalization for total muscle strength (%MRC).", "To evaluate the effects of 4 weeks of hand splinting on the length of finger and wrist flexor muscles, hand function, and pain in people with acquired brain impairment.\n Randomized, assessor-blinded trial.\n Rehabilitation center in Australia.\n Twenty-eight adults with acquired brain impairment, all within 6 months of the first injury. There was 1 withdrawal.\n Subjects in both experimental (n=17) and control (n=11) groups participated in routine therapy-motor training for upper-limb use and upper-limb stretches-5 days a week. The experimental group also wore an immobilizing hand splint in the functional position (10 degrees -30 degrees wrist extension) for a maximum of 12 hours each night for the duration of the 4-week intervention period.\n The length of the wrist and extrinsic finger flexor muscles was evaluated by measuring the torque-controlled range of wrist extension with the fingers extended. Functional hand use was evaluated with the Motor Assessment Scale. Pain was evaluated with a visual analog scale.\n The effects of splinting were statistically nonsignificant and clinically unimportant. At follow-up, estimates of treatment effects slightly favored the control group: range of motion at the wrist favored controls by 2 degrees (95% confidence interval [CI], -7.2 degrees to 3.2 degrees ), function favored controls by 0.2 points (95% CI, -2.7 to 2.3), and pain favored the experimental group by 1cm (95% CI, -4.6 to 2.2).\n An overnight splint-wearing regimen with the affected hand in the functional position does not produce clinically beneficial effects in adults with acquired brain impairment.", "Splints are commonly applied to the wrist and hand to prevent and treat contracture after stroke. However, there have been few randomized trials of this intervention. We sought to determine whether wearing a hand splint, which positions the wrist in either a neutral or an extended position, reduces wrist contracture in adults with hemiplegia after stroke.\n Sixty-three adults who had experienced a stroke within the preceding 8 weeks participated. They were randomized to either a control group (routine therapy) or 1 of 2 intervention groups (routine therapy plus splint in either a neutral or an extended wrist position). Splints were worn overnight for, on average, between 9 and 12 hours, for 4 weeks. The primary outcome, measured by a blinded assessor, was extensibility of the wrist and long finger flexor muscles (angle of wrist extension at a standardized torque).\n Neither splint appreciably increased extensibility of the wrist and long finger flexor muscles. After 4 weeks, the effect of neutral wrist splinting was to increase wrist extensibility by a mean of 1.4 degrees (95% CI, -5.4 degrees to 8.2 degrees), and splinting the wrist in extension reduced wrist extensibility by a mean of 1.3 degrees (95% CI, -4.9 degrees to 2.4 degrees) compared with the control condition.\n Splinting the wrist in either the neutral or extended wrist position for 4 weeks did not reduce wrist contracture after stroke. These findings suggest that the practice of routine wrist splinting soon after stroke should be discontinued.", "In adults undergoing rehabilitation after stroke, does 30 minutes of daily stretch of the wrist and finger flexors for four weeks prevent or reverse contracture, decrease pain, or improve upper-limb activity? Are any gains maintained one week and five weeks after the cessation of stretching?\n Randomised controlled trial with concealed randomisation, assessor blinding, and intention-to-treat analysis.\n 40 adults undergoing rehabilitation after stroke or stroke-like brain injury, who were unable to actively extend the affected wrist.\n Both groups received routine upper-limb retraining five days a week. In addition, the experimental group received 30 minutes daily stretch of the wrist and finger flexors five days a week for four weeks.\n The primary outcome was contracture, measured as torque-controlled passive wrist extension with the fingers extended. Secondary outcomes were pain at rest measured on a 10-cm visual analogue scale, and upper-limb activity measured using the Motor Assessment Scale. Outcomes were collected at baseline, post-intervention, and one and five weeks after cessation of intervention. Results: The mean effect on passive range of wrist extension was 3.8 [corrected] degrees (95% CI -2.5 to 10.1) [corrected] after 4 weeks of daily stretch, 4.1 degrees (95% CI -4.0 to 12.3) after a week of no stretch, and 3.5 degrees (95% CI -4.6 to 11.7) after a further four weeks.\n These data suggest that four weeks of regular stretching has little or no effect on wrist contracture after stroke. However the estimate of the size of this effect is not sufficiently precise to rule out the possibility of a marginally worthwhile effect. The stretch had no significant effect on upper-limb pain, and did not result in significantly improved upper-limb activity.", "Ankle plantar-flexion contractures are a common problem following traumatic head injury. Although serial casting is used to correct and prevent ankle plantar-flexion contractures, treatment efficacy has not been evaluated using an experimental design. The aim of this research was to establish the effect of a regimen of casting combined with stretching on passive ankle dorsiflexion motion.\n Nine people who had sustained traumatic closed head injuries and had limited dorsiflexion motion participated in the study.\n A crossover design was used in the study. Subjects were assigned to both experimental and control groups. Torque-controlled measurements of passive ankle dorsiflexion motion were obtained for all subjects before and after 1 week of casting combined with stretching, as well as before and after a 1-week control period. The order of the experimental and control conditions was randomized.\n Passive ankle dorsiflexion increased by a mean of 13.5 degrees (SD = 9.3) during the experimental condition, as compared with a mean decrease of 1.9 degrees (SD = 10.2) during the control condition. The difference between the experimental and control conditions was statistically significant.\n These findings suggest that casting combined with stretching is an effective method of correcting ankle plantar-flexion contractures in patients with traumatic head injuries.", "To compare the efficacy of short- and long-duration passive stretches with a control treatment for the management of plantarflexion contracture after cast immobilization for ankle fracture.\n Assessor-blinded, randomized controlled trial.\n Hospital physical therapy outpatient departments.\n Adults with plantarflexion contracture (N=150) after cast immobilization for ankle fracture. All subjects were weight bearing or partial weight bearing.\n Exercise only, exercise plus short-duration passive stretch, and exercise plus long-duration passive stretch. All subjects had a 4-week course of exercises. In addition, subjects in the short-duration stretch plus exercise group completed 6 minutes of stretching per day, and subjects in the long-duration stretch plus exercise group completed 30 minutes of stretching per day.\n Lower Extremity Functional Scale and passive dorsiflexion range of motion with the knee bent and straight at baseline, and at 4 weeks and 3 months postintervention.\n One hundred thirty-nine (93%) subjects completed the 4-week assessment and 134 (89%) subjects completed the 3-month assessment. There were no statistically significant or clinically important between-group differences for the primary outcomes.\n The addition of passive stretching confers no benefit over exercise alone for the treatment of plantarflexion contracture after cast immobilization for ankle fracture.", "It was hypothesised that routine splintage following primary total knee replacement has no affect on flexion deformity and offers no benefit over simple wool and crepe. Fifty-five patients undergoing primary total knee replacement were entered into a prospective study. The patients were randomly assigned to two groups: The first group was rehabilitated without a splint and the second received an adjustable semi-rigid extension splint (Richards splint) for the first 48 h after surgery. Range of motion measurements were recorded pre-operatively and at 2 days, 1 week and 3 months post-operation by a research nurse blinded to the allocation. No statistically significant difference in flexion deformity was found at any stage (P>0.5). No difference was found in general or wound complications, or requirement for blood transfusion, and the post-operative stay was equal in the two groups. We conclude that routine use of a semi-rigid splint following primary total knee replacement has no advantage over simple wound dressings.\n Copyright 2002 Elsevier Science B.V.", "To determine the efficacy of positioning the affected shoulder in flexion and external rotation to prevent contracture shortly after stroke.\n Prospective, parallel-group, randomized controlled trial.\n Four metropolitan mixed rehabilitation units.\n A volunteer sample of 36 subjects (minus 5 dropouts), whose mean age was 68 years and had had their first stroke within the past 20 days.\n The experimental group received two 30-minute sessions a day, 5 days a week, for 4 weeks, during which the affected upper limb was placed in maximum comfortable external rotation and 90 degrees of flexion. Both the experimental and control groups received up to 10 minutes of shoulder exercises and standard upper-limb care.\n Contracture was measured as the maximum passive shoulder external rotation and flexion of the affected side as compared with the intact side. Measures were taken at 2 and 6 weeks after stroke by an assessor blinded to group allocation.\n The 30-minute program of positioning the shoulder in maximum external rotation significantly reduced the development of contractures in the experimental group, compared with the control group ( P =.03). The 30-minute program of positioning the shoulder in 90 degrees of flexion did not prevent contractures in the experimental group as compared with the control group ( P =.88).\n At least 30 minutes a day of positioning the affected shoulder in external rotation should be started as soon as possible for stroke patients who have little activity in the upper arm.", "Although contractures in patients in long-term care institutions are an important issue, there have been only a few studies that have evaluated interventions for contractures. The purpose of this study was to determine the effectiveness of a bed positioning program (BPP) for the treatment of patients with knee flexion contractures.\n Sixteen patients with a high level of cognitive and functional impairment (mean age=82 years, SD=6.48, range=71-93) in a chronic care hospital participated in the study.\n The BPP consisted of stretching a patient's knee into extension and then securing and maintaining the position for a period of 40 minutes, 4 times per week. Participants were randomly assigned to 2 groups (n=8 in each group). One group received a BPP for 8 weeks, followed by 8 weeks of no intervention. The other group received the intervention in the reverse order. Once a week, participants were assessed for range of knee extension, knee pain, and skin integrity.\n Twelve participants completed the study. There was no improvement in participants' range of knee extension during the intervention period. Overall, there was no difference in mean range of knee extension between the intervention period and the no-intervention period.\n The results of this study do not support the use of a BPP for treating patients with knee flexion contractures.", "In oral submucous fibrosis (OSF) fibrous bands and burning mucosal pain restrict oral opening to limit speech and eating. The pathogenesis of OSF remains unclear, while surgical and pharmacological treatments have limited success, and are often inaccessible in communities using areca nut where OSF is prevalent. Improved outcomes are reported for surgical treatment when followed by physiotherapy. We tested the hypothesis that physiotherapy alone can modify tissue remodelling in OSF to increase oral opening.\n Fifty-four Nepali OSF patients were managed for 4 months in three randomly assigned groups receiving either: five times daily physiotherapy by inter-positioning tongue spatulas between teeth and adding a new spatula every 5-10 days; local injection of hyaluronidase with steroids; or no active treatment.\n More males presented with OSF than females (p < 0.05). All patients reported reduced opening and 47% had mucosal pain. Progressive mucosal involvement was always in the same order, starting with the soft palate, and then progressing to the fauces, unilateral buccal mucosa, bilateral buccal mucosa, floor of mouth and finally lip mucosa (p < 0.006). Physiotherapy improved oral opening (p < 0.0005), but not oral pain, while no clear improvement was seen in untreated patients as well as patients managed by injection.\n We conclude OSF in the Nepali population progresses in a predictable pattern, and that physiotherapy is effective for increasing the oral opening. We further suggest physiotherapy can be readily used to improve OSF in communities with otherwise limited health resources.", "What is the effectiveness of 12 weeks of nightly stretch in reducing thumb web-space contracture in people with neurological conditions?\n Assessor-blinded, randomised controlled trial.\n Forty-four (one dropout)community-dwelling patients with a neurological condition (14 stroke, 7 traumatic brain injury, 23 spinal cord injury) who had uni or bilateral thumb web-space contractures (60 thumbs).\n The experimental thumbs were splinted into a stretched,abducted position each night for 12 weeks. The control thumbs were not splinted.\n Thumb web-space was measured as the carpometacarpal angle during the application of a 0.9 Nm abduction torque before and after intervention.\n The mean increase in thumb web-space after 12 weeks was 1 deg (95% CI, -1 to 2).\n Intensive stretch administered regularly over three months does not reduce thumb web-space contractures in neurological conditions.", "To quantify the preventive effect of a neutral functional realignment orthosis on pain, mobility, and edema of the hand in subacute hemiparetic poststroke patients with severe motor deficits.\n Randomized trial.\n Rehabilitation center.\n Poststroke patients (N=30) with subacute hemiparesis and severe deficits of the upper limb were enrolled. Fifteen patients were randomized to a standard rehabilitation program without orthosis and 15 patients received an experimental orthosis in addition to their standard rehabilitation program.\n The orthosis group wore the neutral functional realignment orthosis for at least 6 hours daily.\n Hand pain at rest (visual analog scale), wrist range of motion (Fugl-Meyer Assessment subscale), and edema of hand and wrist (circumferences). Outcome measures were assessed at time of randomization and after 13 weeks between groups.\n At baseline, 2 patients in each group complained about a painful hand. After 13 weeks, 8 subjects in the control group and 1 subject in the orthosis group complained of hand pain (P=.004). Mobility and edema evolved similarly in both groups.\n Neutral functional realignment orthoses have a preventive effect on poststroke hand pain, but not on mobility and edema in the subacute phase of recovery.", "Shoulder pain and stiffness is a serious problem in patients following stroke. The purpose of this study was to investigate the effect of a shoulder positioning protocol on shoulder joint pain and range in the affected upper limb. Twenty-eight subjects were randomly assigned to the experimental or control groups and participated in a multidisciplinary rehabilitation program. In addition, the experimental group received prolonged positioning of the shoulder daily for six weeks. Resting pain, pain on dressing, pain-free active abduction and passive external rotation range were measured on entry to the study and after six weeks. Twenty-three subjects completed the study. The differences between the groups were not statistically significant (p < 0.05), however, because of low statistical power the results are inconclusive.", "The aim of this assessor-blind randomised controlled trial was to determine the effect of four weeks of 30 minute stretches each weekday on extensibility of the hamstring muscles in people with recent spinal cord injuries. A consecutive sample of 16 spinal cord-injured patients with no or minimal voluntary motor power in the lower limbs and insufficient hamstring muscle extensibility to enable optimal long sitting were recruited. Subjects' legs were randomly allocated to experimental and control conditions. The hamstring muscles of the experimental leg of each subject were stretched with a 30 Nm torque at the hip for 30 minutes each weekday for four weeks. The hamstring muscles of the contralateral leg were not stretched during this period. Extensibility of the hamstring muscles (hip flexion range of motion with knee extended, measured with a 48 Nm torque at the hip) of both legs was measured by a blinded assessor at the commencement of the study and one day after the completion of the four-week stretch period. Changes in hamstring muscle extensibility from initial to final measurements were calculated. The effect of stretching was expressed as the mean difference in these changes between stretched and non-stretched legs. The mean effect of stretching was 1 degree (95% CI -2 to 5 degrees). Four weeks of 30 minute stretches each weekday does not affect the extensibility of the hamstring muscle in people with spinal cord injuries.", "A controlled study of 39 consecutively-admitted patients with ankylosing spondylitis was conducted to assess the effects of daily passive stretching of the hip joints during a 3-week in-patient physiotherapy course. Measurements were performed by an independent assessor on admission, at discharge and six months after discharge. Results showed that passive stretching resulted in a significant increase in the range of all movements of the hip joints except flexion during the physiotherapy course. Follow-up at 6 months in seven patients suggested that this increase in range of movement could be maintained by patients who had been performing the stretching exercises regularly. We suggest that the inclusion of passive stretching of the hip joint in the treatment of patients with ankylosing spondylitis will increase the range of movement and thus improve function and influence posture.", "To evaluate the effects of a rehabilitation brace locked in extension for the first week on the recovery of full extension after ACL reconstruction we compared two groups of subjects who underwent ACL bone-patellar tendon-bone reconstruction. The brace was unlocked twice a day for assisted physiotherapy. In Group A, 18 male subjects wore a post-operative brace locked from 0 degrees to 90 degrees. In Group B, 18 male subjects wore the same post-op brace locked in full extension for the first week. In both groups the brace was unlocked (0 degrees -120 degrees ) at the beginning of the second postoperative week, and then removed at the beginning of the third week. All the subjects followed the same rigorous, accelerated rehabilitation protocol. Each subject was evaluated pre and post-operatively (at second, fourth and eighth week) with bubble-level heel height difference (HHD) measurements and KT 1000 arthrometric assessment at the fourth postoperative month. Preoperative bubble-level HHD measurements of the two groups were statistically similar (Group A 0.6 cm, Group B 1 cm; not significant, n.s.). At the fourth week (Group A 2.2 cm, Group B 0.6 cm) and eighth week (Group A 1.6 cm, Group B 0.1 cm) follow-ups, bubble-level HHD measurements showed that the extension of the operated knees of Group B was significantly greater than in Group A. KT 1000 arthrometric scores showed no difference between the two groups (Group A 1.8 mm, Group B 1.5; n.s.).", "One of the major factors in the decreasing functional ability of patients with progressive systemic sclerosis is involvement of the patient's hands with secondary immobility and contractures. In a 2-month study of 19 patients, we assessed whether dynamic splinting could decrease proximal interphalangeal (PIP) flexion contractures. Of the eight patients who completed the study, one experienced a statistically significant improvement in PIP range of motion as a result of the splinting. There was no evidence that the use of the splints served to maintain PIP extension when compared with the control hand.", "The purpose of this research was to study the effect of intensive neurodevelopmental therapy (NDT) and upper-extremity inhibitive casting, separately or in combination, on hand function, quality of upper-extremity movement and range of motion of 73 children with spastic cerebral palsy aged 18 months to eight years. There was no significant difference between intensive or regular therapy and casting or no casting for hand function, between intensive and regular NDT, or between intensive NDT plus casting and the other groups for quality of movement and range of motion. Casting led to increased quality of movement and wrist extension after six months. Casting with NDT improved the quality of upper-extremity movement and range of motion. There appear to be no immediate benefits from intensive therapy alone.", "Much has been written about the use of static orthoses to maintain proper position and prevent deformity, but there are few empirical data to determine whether static orthoses improve function, maintain range of motion, or prevent deformity in the hand.\n This study measured gains in hand function during a 3-month rehabilitation period in 13 persons with sixth cervical (C-6) level complete quadriplegia, 7 of whom wore a static orthosis at night (experimental group) and 6 who did not wear the orthosis (control group). Hand function, range of motion and strength were measured in all subjects 4 weeks and 8 weeks after the study commenced, and again after 12 weeks in only 69% of the subjects.\n No significant differences were found in hand function between control and experimental groups; hand function had improved significantly in all 13 subjects.\n As the effects of deformity have been clinically observed, future studies should examine the effects of static orthoses with increased daily wear or wear over a longer period of time.", "To obtain the best estimate of the size of the effect of a thermoplastic resting splint on spasticity in the stroke-affected upper limb.\n A randomized controlled intervention involving 14 adults affected by stroke,allocated to two groups.\n Inpatient and outpatient rehabilitation departments.\n Following one week of baseline when neither group wore a splint, group 1 continued without a splint for week 2 and then wore a splint during week 3. Group 2 wore a splint during weeks 2 and 3. Both groups then wore a splint through weeks 4-7.\n A computerized torque apparatus was used to measure resistance at the wrist in newtons at every one-degree angle through the range of extension. Amount and rate of change in resistance was compared between the groups to obtain the best estimate of the size of the effect of splinting.\n Effect sizes were small and failed to reach the suggested smallest clinically worthwhile effect size for amount and rate of change in resistance in the short term. However, the average estimated size of the effect for rate of change with longer term splinting exceeded the smallest clinically worthwhile effect.\n These findings and the fact that confidence intervals overlapped the smallest clinically worthwhile size of the effect for amount and rate of change in both short and long term suggest that a study with a larger sample is warranted.", "Surgery and radiotherapy commonly cause adverse musculoskeletal problems, particularly loss of strength and range of motion, in the upper quadrant of breast cancer patients. Few well-designed studies have investigated whether these impairments can be prevented. Stretching is an effective technique for increasing range of motion, hence the aim of this study was to investigate whether a stretching program reduced acute musculoskeletal impairments in patients undergoing radiotherapy for breast cancer. Sixty-four women were recruited prior to commencement of radiotherapy following breast cancer surgery. Participants were randomised to either a control or stretch group. Participants in both groups were reviewed by the physical therapist on a weekly basis for approximately 6 weeks, and were given general information about skin care and lymphedema. The control group received no advice about exercise. The stretch group received instruction on low-load, prolonged pectoral stretches, which were to be performed daily and were checked at weekly visits. Shoulder range of motion, strength, arm circumference, and quality of life measurements were taken prior to, and at completion of radiotherapy, and at 7 months after radiotherapy. There was no difference in any outcome between groups. Breast symptoms increased for both groups during radiotherapy, without loss of strength or range of movement. The incidence of lymphedema during the study was low for both groups and did not differ between groups. The pectoral stretching program did not influence the outcomes measured because the symptoms reported by patients were not a consequence of contracture.", "The purpose of this study was to determine the effects of a 12-week standing program on ankle mobility and femur bone mineral density in patients with lower limb paralysis following recent spinal cord injury. An assessor-blinded within-subject randomised controlled trial was undertaken. Twenty patients with lower limb paralysis following a recent spinal cord injury were recruited. Subjects stood weight-bearing through one leg on a tilt-table for 30 minutes, three times each week for 12 weeks. By standing on one leg a large dorsiflexion stretch was applied to the ankle and an axial load was applied to the bones of the weight-bearing leg. Ankle mobility and femur bone mineral density of both legs were measured at the beginning and end of the study. Ankle mobility (range of motion) was measured with the application of a 17 Nm dorsiflexion torque. Femur bone mineral density was measured using dual energy X-ray absorptiometry (DEXA). The effect of standing was estimated from the difference between legs in mean change of ankle mobility and femur bone mineral density. The results indicated a mean treatment effect on ankle mobility of 4 degrees (95% CI 2 to 6 degrees) and on femur bone mineral density of 0.005 g/cm(2) (95% CI -0.015 to 0.025 g/cm(2)). Tilt-table standing for 30 minutes, three times per week for 12 weeks has a small effect on ankle mobility, and little or no effect on femur bone mineral density. It is unclear whether clinicians and patients would consider such effects to be clinically worthwhile.", "To investigate the effectiveness of a contracture preventive positioning procedure for the hemiplegic arm in subacute stroke patients in addition to conventional physio- and occupational therapy.\n A single-blind pilot randomized controlled trial.\n Inpatient neurological units from three rehabilitation centres in the Netherlands.\n Nineteen subacute stroke patients (minus two drop-outs) with a severe motor deficit of the arm.\n All subjects underwent conventional rehabilitation care. Nine subjects additionally received a positioning procedure for two 30-min sessions a day, five days a week, for five weeks.\n Passive range of motion of five arm movements using a hydrogoniometer and resistance to passive movement at the elbow using the Ashworth Scale. Secondary outcome measures were pain at the end range of passive motions, the arm section of the Fugl-Meyer Assessment and Barthel Index scores for ADL-independence. Outcome measures were taken after five weeks and additional measurements after 10 weeks by two assessors blinded to group allocation.\n Comparison of the experimental (n = 9) with the control subjects (n = 8) after five weeks showed that additional positioning significantly slowed down development of shoulder abduction contracture (P = 0.042, -5.3 degrees versus -23 degrees). No other differences were found between the groups.\n Applying a contracture preventive positioning procedure for the hemiplegic arm slowed down the development of shoulder abduction contracture. Positioning did not show significant additional value on other outcome measures. Since the sample size was small, results of this study need future verification.", "Over 1.5 million Americans are diagnosed with a stroke each year, and excessive flexion or extension (hypertonia) of upper extremity joints are common secondary conditions. The purpose of this study was to compare the efficacy of botulinum toxin type-A and manual therapy, with the adjunct treatment of dynamic splinting on range of motion, spasticity, and elbow flexor hypertonia, in a randomized trial.\n Thirty-six subjects were recruited for this pilot study and all exhibited hypertonia in elbow flexion. Six patients were excluded due to noncompliance. Testing was done with pre/post active range of motion in elbow extension, and the Modified Ashworth Scale (extension) for spasticity. All patients received the current standard of care: botulinum toxin type-A injections and manual therapy. Experimental patients were randomly assigned adjunct treatment with Elbow Extension Dynasplint.\n Thirty patients completed the study (mean age [SD] 52+/-17 years). The percentage of change in active range of motion in elbow extension was greater for the experimental than for control subjects (33.5% vs. 18.7%). The Modified Ashworth Scale (extension) scores showed comparable changes of a mean 9.3% improvement for experimental versus 8.6% for the control subjects.\n This study confirmed the efficacy of botulinum toxin type-A in tone management and occupational therapy in contracture reduction. It also showed the value of dynamic splinting in maintaining gains in range of motion.", "To determine the effect of 4 weeks of 30 minutes of daily stretching on ankle mobility in patients with recent spinal cord injuries (SCIs).\n Assessor-blinded randomized controlled trial.\n Two spinal injury units in Sydney, Australia.\n Consecutive sample of 14 recently injured patients with paraplegia and quadriplegia.\n Treated ankles were stretched continuously into dorsiflexion with a torque of 7.5 N x m for 30 minutes each weekday for 4 weeks. Contralateral ankles received no stretches.\n Passive torque-angle curves for both ankles were obtained at study commencement, then at weeks 2, 4, and 5 (ie, during, at the end of, and 1 week after the stretching program). Torque-angle measurements were obtained with the knee extended and flexed. Mean values for parameters (baseline angle, angle at 10 N x m, slope) describing the characteristics of the torque-angle curves were derived for each knee position. Changes from pretest to each subsequent test were calculated, as well as 95% confidence intervals (CIs) for differences in these changes between stretched and controlled ankles.\n The stretching intervention did not significantly change any of the 3 parameters describing the torque-angle curves of the ankle in either knee position. At the beginning of the study, the mean (+/-SD) angles obtained with the application of a standardized torque with the knee extended for the control and stretch ankles were 105 degrees (+/- 10.4 degrees) and 106 degrees (+/- 9.8 degrees), respectively. After 4 weeks, these values were 106 degrees (+/- 10.6 degrees) and 107 degrees (+/- 10.6 degrees) (mean difference in change of angle = 0 degrees; 95% CI, -3.3 degrees to 3.3 degrees).\n Thirty minutes of daily stretching for 4 weeks does not significantly change ankle mobility in recently injured patients with SCIs." ]

[ "14033615", "7778622", "6781613", "12375540", "2205188" ]

[ "Effect of oestrogens on myometrial contractions.", "Cervical ripening before medical induction of labor: a comparison of prostaglandin E2, estradiol, and oxytocin.", "Comparative study of oestradiol and prostaglandin E2 vaginal gel for ripening the unfavourable cervix before induction of labour.", "Outpatient cervical ripening with prostaglandin E2 and estradiol.", "A randomized controlled trial of extra-amniotic ethinyloestradiol for cervical ripening in multiparas." ]

[ "nan", "Our purpose was to evaluate the effectiveness of oxytocin, prostaglandin E2 intracervical gel, and estradiol cream for ripening the very unfavorable cervix in patients requiring induction of labor at term.\n This prospective, randomized study was conducted in a population of women with a very unfavorable cervix (Bishop score < 4) requiring induction of labor. The patients received prostaglandin E2 gel (0.5 mg) intracervically (three doses 6 hours apart), 4 mg estradiol cream in the anterior fornix of the vagina (three doses 6 hours apart), or oxytocin at induction per protocol with an infusion pump.\n Ninety-nine women were recruited into this trial and evenly distributed among the three groups. The demographics of maternal age, race, parity, gestational age, initial Bishop score, and indication for induction were similar among the groups. The incidence of cesarean deliveries was similar in the three groups with approximately 59% of pregnancies delivered abdominally. For patients undergoing abdominal delivery the maximum cervical dilatation among the oxytocin, estradiol, and prostaglandin E2 groups was similar (3.90 +/- 3.02 cm, 3.63 +/- 2.79 cm, and 4.65 +/- 2.78 cm, respectively; p > 0.05). For all patients birth weight and Apgar scores at 1 and 5 minutes were comparable across all regimens (p > 0.05). In the subset of patients delivered vaginally patients receiving oxytocin for cervical ripening had the greatest improvement in Bishop score over baseline (p = 0.023) with an improvement of 7.08 +/- 2.42.\n No differences were detected among prostaglandin E2 gel, estrogen, and oxytocin in relation to cervical ripening in patients with an unfavorable cervix at term who require an induction of labor. Patients with a very unfavorable cervix at term who require delivery may benefit from serial ripening and inductions.", "Oestradiol 150 mg and prostaglandin E2 (PGE2) 4 mg suspended in viscous gel and applied intravaginally were compared with regard to ripening the unfavourable cervix of patients randomly allocated to two study groups. In primigravidae no significant difference was observed in the efficacy of the two substances. Some multiparous patients, however, had considerably more uterine sensitivity to PGE2 quickly developed decelerative cardiotocographic tracings after insertion of the gel. In the group given oestradiol there was a significant absence of uterine activity after gel application. The findings suggest that oestradiol applied vaginally is a safe, comfortable, cheap, and equally effective alternative to PGE2 for ripening the cervix, without the disadvantages of uterine stimulation frequently encountered with PGE2.", "To determine whether weekly outpatient administration of prostaglandin gel or estrogen cream initiated labor in women with an unfavorable cervix.\n All uncomplicated pregnancies at term gestation who were candidates for a vaginal delivery with a Bishop score of < or = 6 were randomly assigned to receive on a weekly basis: prostaglandin E2 gel (n = 41); estrogen cream (n = 44); or inert lubricant jelly (n = 43).\n In the three groups no differences were observed among 128 subjects in the weekly Bishop scores, cervical dilatation or gestational age upon admission to the labor and delivery suite, the percentage of patients presenting with spontaneous labor or ruptured membranes, the number of post-date inductions or neonatal outcome.\n Weekly out-patient cervical ripening using either prostaglandin gel or estrogen in women with an unfavorable cervix at 37 weeks' gestation was no more effective than a placebo in Bishop score improvement or in preventing post-date inductions.", "A double-blind randomized controlled trial was carried out to determine if ethinyloestradiol applied extra-amniotically would ripen the unfavourable cervix at term. Twenty five multiparas were given 150 mg ethinyloestradiol gel while 25 multiparas were given gel alone. There was no difference between the ethinyloestradiol and control groups in either mean change of Bishop score or the induction-to-delivery interval." ]

[ "6580858", "3933645", "3915841" ]

[ "Intravenous methylprednisolone pulse therapy in minimal change nephrotic syndrome.", "Controlled trial of methylprednisolone pulses and low dose oral prednisone for the minimal change nephrotic syndrome.", "Adult minimal change nephropathy: experience of the collaborative study of glomerular disease." ]

[ "The effectiveness of intravenous methylprednisolone pulses in 20 mg/kg/day for three consecutive days was compared with a more conventional oral prednisone regime in inducing remission in adult patients presenting with first episodes of minimal change nephrotic syndrome. Methylprednisolone was significantly less effective and failed to induce remission in six of nine patients within two weeks of treatment, while the oral prednisone regime was uniformly effective in all eight patients within five weeks. Of the six non-responders to methylprednisolone five subsequently remitted with oral prednisone, and one with cyclophosphamide. Except for one patient in the oral prednisone group who had acute gastritis with bleeding, no serious side-effect was seen with either treatment regimes.", "In a multicentre, randomised, prospective trial 89 patients (67 children and 22 adults) with the minimal change nephrotic syndrome were treated with three intravenous pulses of methylprednisolone followed by low dose oral prednisone for six months (group given methylprednisolone) or with high dose oral prednisone for four weeks followed by low dose oral prednisone for five months (control group). Five patients in the group given methylprednisolone and one in the control group did not respond initially. The time to response was shorter in children treated with methylprednisolone. No significant differences between the two groups were observed in the number of patients who relapsed or number of relapses per patient per year. Patients given methylprednisolone tended to relapse earlier than patients in the control group. Side effects related to treatment were significantly fewer in the group given methylprednisolone than in the control group. These data suggest that a short course of methylprednisolone pulses followed by low dose oral prednisone is only marginally less effective than a regimen of high dose oral steroids but can improve the ratio of risk to benefit associated with treatment of the minimal change nephrotic syndrome.", "nan" ]

[ "11836799", "10700685", "15078738", "15563708", "2748718" ]

[ "Randomized controlled study of in-hospital exercise training programs in children with cystic fibrosis.", "A randomized controlled trial of a 3-year home exercise program in cystic fibrosis.", "Effects of anaerobic training in children with cystic fibrosis: a randomized controlled study.", "Individualised unsupervised exercise training in adults with cystic fibrosis: a 1 year randomised controlled trial.", "Relative effects of bronchial drainage and exercise for in-hospital care of patients with cystic fibrosis." ]

[ "The aim of this study was to compare aerobic and resistance training in children with cystic fibrosis (CF) admitted to hospital with an intercurrent pulmonary infection with a control group. The subjects were randomized into three groups on the first day of admission. The fat-free mass (FFM) was calculated, using the skin fold thickness from four sites (biceps, triceps, subscapular, and iliac crest). Pulmonary function tests were performed within 36 hr of admission and repeated on discharge from the hospital, and again at 1 month after discharge. All subjects performed an incremental treadmill exercise test, using a modified Bruce protocol. Lower limb strength was measured using a Cybex dynamometer. An assessment of quality of life was made using the Quality of Well Being Scale, as previously reported. Activity levels were measured using a 7-day activity diary, and subjects also wore an accelerometer on their hips. There were no significant differences between the three groups in terms of disease severity, and length of stay in hospital. Subjects in all three groups received intravenous antibiotics and nutritional supplementation as determined by the physician. Children randomized to the aerobic training group participated in aerobic activities for five sessions, each of 30-min duration, a week. The children randomized to the resistance training group exercised both upper and lower limbs against a graded resistance machine. Subjects in the control group received standard chest physiotherapy. Our study demonstrated that children who received aerobic training had significantly better peak aerobic capacity, activity levels, and quality of life than children who received the resistance training program. Children who received resistance training had better weight gain (total mass, as well as fat-free mass), lung function, and leg strength than children who received aerobic training. A combination of aerobic and resistance training may be the best training program, and future studies to assess optimal training programs for CF patients are indicated.\n Copyright 2002 Wiley-Liss, Inc.", "To evaluate the effects of a 3-year home exercise program on pulmonary function and exercise tolerance in mildly to moderately impaired patients with cystic fibrosis (CF) and to assess whether regular aerobic exercise is a realistic treatment option.\n Seventy-two patients with CF (7-19 years) were randomly assigned to an exercise group (a minimum of 20 minutes of aerobic exercise, at a heart rate of approximately 150 beats/min, 3 times weekly) or a control group (usual physical activity participation). Pulmonary function, exercise tolerance, clinical status, hospitalizations, and compliance with therapy were monitored during scheduled visits to the hospital's CF clinic.\n Sixty-five patients were included in the analyses. The control group demonstrated a greater annual decline in percent of predicted forced vital capacity compared with the exercise group (mean slope +/- SD, -2.42 +/- 4.15 vs -0.25 +/- 2.81; P =.02), with a similar trend for forced expiratory volume in 1 second (-3.47 +/- 4.93 vs -1.46 +/- 3. 55; P =.07). Patients remained compliant with the exercise program over the study period. An improved sense of well-being was reported with exercise.\n Pulmonary function declined more slowly in the exercise group than in the control group, suggesting a benefit for patients with CF participating in regular aerobic exercise. Consistent compliance with the home exercise program and a self-reported positive attitude toward exercise provide further evidence of the feasibility and value of including an aerobic exercise program in the conventional treatment regimen of patients with CF.", "Children's physical activity patterns are characterized by short-term anaerobic activities. Anaerobic exercise performance in children with cystic fibrosis (CF) has received little attention compared to aerobic performance. This study investigated the effects of anaerobic training in children with CF.\n Twenty patients were randomly assigned to the training group (TG) [11 patients; mean (+/- SD) age, 13.6 +/- 1.3 years; mean FEV(1), 75.2 +/- 20.7% predicted] or the control group (CG) [9 patients; mean age, 14.2 +/- 2.1 years; FEV(1), 82.1 +/- 19.1% predicted]. The TG trained 2 days per week for 12 weeks, with each session lasting 30 to 45 min. The training program consisted of anaerobic activities lasting 20 to 30 s. The control subjects were asked not to change their normal daily activities. Body composition, pulmonary function, peripheral muscle force, habitual physical activity, aerobic and anaerobic exercise performance, and quality of life were reevaluated at the end of the training program, and again after a 12-week follow-up period.\n Patients in the TG significantly improved their anaerobic performance, aerobic performance, and quality of life. No significant changes were seen in other parameters, and no improvements were found in CG. After the follow-up period, only anaerobic performance and quality of life in TG were significantly higher compared to pretraining values.\n Anaerobic training has measurable effects on aerobic performance (although not sustained), anaerobic performance, and health-related quality of life in children with CF. Therefore, anaerobic training could be an important component of therapeutic programs for CF patients.", "Short term studies of exercise training have shown benefits in cystic fibrosis. Transferring exercise programmes to the community and sustaining them long term is a challenge for the patient. The effectiveness of an individualised unsupervised home based exercise programme was examined in adults with cystic fibrosis over a 1 year period.\n Subjects were randomised to undertake three sessions per week of upper and lower body exercise based on individualised preferences (n = 30) or to a control group (n = 18). They were evaluated at baseline and at 12 months. The primary outcome measure was improved fitness as assessed by change in blood lactate concentration at the end of an identical constant work rate for both arm and leg ergometric testing. Secondary outcome measurements were heart rate and pulmonary function.\n For leg exercise, significant differences were seen at 12 months between the active and control groups in the mean (SE) change in blood lactate levels (-0.38 (0.23) mmol/l v 0.45 (0.25) mmol/l, p<0.05) and heart rate (-4.8 (2.5) bpm v 3.4 (2.5) bpm, p<0.05), confirming a training effect. For arm ergometry there was no change in lactate levels at 12 months but there was a significant difference in forced vital capacity (46 (72) ml v -167 (68) ml, p<0.05).\n A training effect, as measured by a reduction in lactate levels and heart rate, can be achieved with unsupervised individualised home exercise in adults with cystic fibrosis. A benefit to pulmonary function was observed and together these findings suggest that exercise programmes should be encouraged as an important component of care in cystic fibrosis.", "Bronchial hygiene therapy is a standard part of the treatment of patients with cystic fibrosis (CF). Coughing alone promotes sputum expectoration and is probably the primary effective component of standard bronchial hygiene therapy. The purpose of this study was to determine whether substituting regular exercise, which also promotes coughing, for two of three daily bronchial hygiene treatments would affect the expected improvements in pulmonary function and exercise response in hospitalized patients with CF. Seventeen patients with CF hospitalized (means length of stay = 13.0 +/- 2.6 days) for an acute exacerbation of their pulmonary disease participated in the study. The patients were randomly assigned to either a group that participated in two cycle ergometer exercise sessions and one bronchial hygiene treatment session per day (EX Group [n = 9]) or a group that participated in three bronchial hygiene treatment sessions per day (PD Group [n = 8]). Pulmonary functions and responses to a progressive, incremental cycle ergometer exercise test were measured on admission and before discharge. Bronchial hygiene therapy consisted of postural drainage, in six positions, with chest percussion and vibration. Therapeutic exercise was of moderate intensity and was individually adjusted based on the patient's heart rate and arterial oxygen saturation response to the admission exercise test. Coughing was encouraged during and after all treatments. Pulmonary function and exercise response were significantly improved over the period of hospitalization in both groups; the improvements were the same in the two groups. These results indicate that, in some hospitalized patients with CF, exercise therapy may be substituted for at least part of the standard protocol of bronchial hygiene therapy." ]

[ "9802132", "10566625", "11403980", "15989411", "17050889", "18482290" ]

[ "Opposing effects of DHEA replacement in elderly subjects on declarative memory and attention after exposure to a laboratory stressor.", "The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life.", "Salivary cortisol and DHEA: association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation.", "Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids.", "DHEA in elderly women and DHEA or testosterone in elderly men.", "Effects of dehydroepiandrosterone supplementation on cognitive function and quality of life: the DHEA and Well-Ness (DAWN) Trial." ]

[ "Aging is accompanied by a continuous decline of the adrenal steroid hormone DHEA and its ester DHEAS. Results from studies in rodents have demonstrated that DHEA(S) administration can enhance memory in several test paradigms. However studies from this laboratory did not find positive effects of DHEA treatment on cognitive performance in young and elderly humans. With respect to a possible mechanism of DHEA activity, effects on several neurotransmitter receptors as well as a possible antiglucocorticoid action are discussed. For high levels of glucocorticoids, a disruptive effect on hippocampal mediated memory is documented in rodents and humans. Therefore it was speculated that, if an antiglucocorticoid action of DHEA would underlie the observed beneficial effects of DHEA on memory, these effects might only be detectable if subjects are stressed (and therefore have high cortisol levels). To test this hypothesis 75 elderly women and men participated in a placebo controlled experiment. Subjects took DHEA (50 mg/day) or placebo for 2 weeks (double blind). Thereafter they participated in a standardized psychosocial laboratory stressor (Trier Social Stress Test; TSST). Before and after stress exposure subjects completed two declarative memory tests (visual-verbal and spatial) as well as one attention test. In addition recall of visual material learned before stress was assessed after stress. Baseline DHEAS levels were significantly lower compared with young adults. DHEA replacement increased DHEAS levels into ranges found in young subjects. DHEA-substituted subjects showed a trend towards a larger cortisol stress response. In the visual memory test subjects under DHEA recalled less items after stress which they had learned before stress. In the attention test however subjects under DHEA performed better than subjects from the placebo group after stress. No interaction between stress and DHEA was found for the spatial memory task. The effects of DHEA substitution on memory and attention after stress exposure seem to be heterogenous. While recall of previously learned material seems to be impaired, attention is enhanced. These results do not support the idea of a direct antiglucocorticoid or anti-stress effect of DHEA on hippocampal mediated memory functions.", "Dehydroepiandrosterone (DHEA), an androgenic steroid hormone, exhibits an age-related decline. Perimenopausal women have only approximately 50% of peak DHEA levels. Despite limited scientific data, DHEA has gained recognition as a dietary supplement to reduce the symptoms of aging and improve well-being. This randomized, double-blind placebo-controlled trial examined the effects of 50 mg/day of oral DHEA supplementation, for 3 months, on 60 perimenopausal women with complaints of altered mood and well-being. Changes in the serum endocrine profile of women in the DHEA group were significantly greater than the placebo group, including a 242% [95% confidence interval (CI) +60.1, +423.9] increase in DHEAS, a 94.8% (95% CI +34.2, +155.4) increase in testosterone, and a 13.2% (95% CI -27.88, +0.5) decline in cortisol compared to baseline. Women receiving DHEA had a 10.1% (95% CI -15.0, -5.1) decline in high-density lipoprotein and an 18.1% (95% CI -32.2, -3.9) decline in Lp(a) from baseline, but these declines did not significantly differ from women who received placebo. Women receiving DHEA did not have any improvements significantly greater than placebo in the severity of perimenopausal symptoms, mood, dysphoria, libido, cognition, memory, or well-being. DHEA supplementation significantly effects the endocrine profile, may affect the lipid profile, but does not improve perimenopausal symptoms or well-being compared to placebo.", "Dehydroepiandrosterone (DHEA) is a steroid that shows a marked age-related decline in humans. Previous research suggests potential for DHEA replacement in old age to enhance cognition and well-being. We conducted a clinical trial to test these hypotheses in a non-clinical sample of 46 men aged 62-76. Participants received either 50 mg DHEA daily for 13 weeks, followed by placebo for 13 weeks, or the reverse, in a randomised double-blind cross-over trial design. Levels of salivary cortisol and DHEA were measured at 0800 h and 2000 h prior to each assessment session. Cognition was assessed with tests of speed, attention and episodic memory. Well-being was measured with questionnaires of mood and perceived health. Mood questionnaires were completed at the assessment session as well as concurrently with saliva sampling.A correlational analysis of baseline behavioural data with hormonal data, controlling for age, revealed that higher morning DHEA was associated with lower confusion (r=-0.33; P=0.04), while higher evening DHEA was associated with lower anxiety (r=-0.35; P=0.03) and lower current negative mood in the morning (r=-0.37; P=0.03). Conversely, higher morning cortisol and a morning cortisol/DHEA ratio were associated with higher anxiety (r=0.35; P=0.03), (r=0.46; P=0.004), general mood disturbance (r=0.32; P=0.046), (r=0.32; P=0.04) and higher current negative mood in the evening (r=0.37; P=0.03), (r=0.38; P=0.03). A higher morning cortisol/DHEA ratio was also associated with higher confusion (r=0.39; P=0.01) and lower visuo-spatial memory performance (r=-0.39; P=0.01). Unexpectedly, higher evening cortisol was associated with faster choice reaction time (r=-0.33; P=0.04). These findings are consistent with an impairing effect of high cortisol on episodic memory and mood in older men, which may be attenuated by DHEA. When treatment effects were analysed, no significant effects of DHEA were observed on any of the trial outcomes, providing no support for benefits of DHEA supplementation for cognition or well-being in normal older men in the shorter-term.", "To evaluate the effects of combination estrogen/androgen therapy on muscle mass, strength and endurance, serum hormone and lipid profiles, and quality of life measures in postmenopausal women.\n Prospective, randomized, placebo-controlled pilot study at a tertiary care medical center. Fifty postmenopausal women were randomized to a 12-week course of (1) dehydroepiandrostenedione (DHEA) 50 mg daily, (2) conjugated equine estrogen (CEE) 0.625 mg daily, (3) DHEA 50 mg+CEE 0.625 mg daily, or (4) placebo. Main outcome measures of lower extremity muscle (calf) mass, functional muscle parameters, serum hormone and lipid levels, and quality of life (QOL) were obtained at baseline and after treatment. Statistical analysis compared percent change from baseline values and treatment differences among outcomes.\n Significant increases in mean DHEA, DHEA sulfate (DHEA-S), testosterone, and androstenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo. Compared with no hormone therapy, none of the supplemental hormone groups caused significant changes in muscle mass, muscle strength, muscle endurance, feelings of well-being, sleep, or sexual function.\n Androgen replacement therapy, with DHEA, to menopausal women increases serum androgen levels without any appreciable effect on muscle cross-sectional area, muscle strength, muscle function, or improvement in health-related QOL.", "Dehydroepiandrosterone (DHEA) and testosterone are widely promoted as antiaging supplements, but the long-term benefits, as compared with potential harm, are unknown.\n We performed a 2-year, placebo-controlled, randomized, double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo. Among the women, 27 received DHEA and 30 received placebo. Outcome measures included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life.\n As compared with the change from baseline to 24 months in the placebo group, subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter (9.2 micromol per liter) in men and by 3.8 microg per milliliter (10.3 micromol per liter) in women. Among men who received testosterone, the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter (1.1 nmol per liter), as compared with the change in the placebo group. A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute, muscle strength, or insulin sensitivity. Men who received testosterone had a slight increase in fat-free mass, and men in both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultradistal radius. Neither treatment improved the quality of life or had major adverse effects.\n Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. (ClinicalTrials.gov number, NCT00254371 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society.", "To examine the effects of dehydroepiandrosterone (DHEA) supplementation on cognitive function and quality of life in healthy older adults.\n Double-blind, randomized, controlled clinical trial.\n Clinical research facility.\n One hundred ten men and 115 women aged 55 to 85 (mean +/- standard deviation 68 +/- 8).\n Fifty milligrams daily oral DHEA versus placebo for 1 year.\n Six cognitive function tests at baseline and 12 months, the Beck Depression Inventory (BDI), the Medical Outcomes Study 36-item Short Form Survey (SF-36), the Life Satisfaction Index-Z, the Satisfaction with Life Scale, the Female Sexual Function Index (in women), and the 15-item International Index of Erectile Function (in men) at baseline and 3, 6, and 12 months.\n There were no differences between the DHEA and placebo groups in change over time in cognitive function (P>.10). Over time, BDI scores decreased for men (P=.006) and women (P=.02), and Satisfaction with Life Scale scores increased for women (P=.004), but there were no differences between the DHEA and placebo groups over time on these measures or the SF-36, Life Satisfaction Index-Z scale, or sexual function scales (P>.10).\n DHEA supplementation has no benefit on cognitive performance or well-being in healthy older adults, and it should not be recommended for that purpose in the general population." ]

[ "20237485", "16724119", "16837929" ]

[ "High-flow nasal cannula and extubation success in the premature infant: a comparison of two modalities.", "Comparing two methods of delivering high-flow gas therapy by nasal cannula following endotracheal extubation: a prospective, randomized, masked, crossover trial.", "Nasal continuous positive airway pressure from high flow cannula versus Infant Flow for Preterm infants." ]

[ "To compare the effectiveness of Fisher and Paykel (FP) and Vapotherm (VT) high-flow nasal cannula (HFNC) in preventing reintubation either within 72 h or <7 days after extubation of premature infants. The primary outcome was the rate of extubation failure defined as reintubation within 72 h. Secondary outcomes included reintubation after ≤7 days.\n This was a prospective, randomized pilot study comparing the extubation success of 40 infants born between 26 and 29 weeks of gestation.\n The rate of extubation failure at 72 h was 18% for FP and 9% for VT. The failure rate ≤7 days after extubation was 30% for FP and 27% for VT. None of these differences were statistically significant.\n There was no difference between FP and VT in the extubation success of infants born between 26 and 29 weeks.", "We compared two methods of delivering high-flow gas therapy by nasal cannula, applied immediately after planned endotracheal extubations of NICU patients.\n Thirty NICU patients who were about to be extubated from mechanical ventilation were randomized into two groups; Group 1 received Vapotherm for the first 24 h after extubation, then standard high-flow nasal cannula for the next 24 h, and Group 2 received standard high-flow therapy for the first 24 h, then Vapotherm for the next 24 h. At 24 h after extubation and again 48 h after extubation, a neonatologist who was not aware which modality the patient had been receiving examined the nasal mucosa and applied a scoring system. A research nurse who was unaware of the modality abstracted respiratory rates and respiratory effort scores from a specific study-bedside record. The experimental design was such that a patient could 'fail' extubation either by reintubation for mechanical ventilation, or by rescue to the opposite modality before completing the 24-h test period.\n Fifteen patients were randomized to Group 1 and 15 to Group 2. No differences were apparent between the groups in birth weight, gestational age, age at study entry, gender or underlying pulmonary disorder. Respiratory rates were similar while on Vapotherm (52+/-13 breaths/min, mean+/-s.d.) and high-flow (54+/-14/min). At 24 h after starting the modality, those on Vapotherm had more normal examinations of the nasal mucosa (2.7+/-1.2 vs 7.8+/-1.7, P < 0.0005) and lower respiratory effort scores (1.2+/-0.6 vs 2.0+/-0.9, P < 0.05) than did those on high-flow. No patients failed while on Vapotherm, but seven failed while on high-flow (two reintubations and five rescue switches to Vapotherm, P < 0.005).\n Among NICU patients immediately following extubation, Vapotherm performed better than a standard high-flow nasal cannula in maintaining a normal appearing nasal mucosa, a lower respiratory effort score, and averting reintubation.", "To compare the feasibility of continuous positive airway pressure (CPAP) support generated by high flow nasal cannula with conventional CPAP for prevention of reintubation among preterm infants with a birth weight of <or=1,250 g.\n Preterm infants were randomized to CPAP generated via high flow cannula or the Infant Flow Nasal CPAP System (VIASYS, Conshohocken, PA, USA) at extubation. Primary outcome was incidence of reintubation within 7 days. Secondary outcomes included change in oxygen use and frequency of apnea and bradycardias postextubation.\n Forty neonates were randomized. Twelve of 20 infants randomized to high flow cannula CPAP were reintubated compared to three of 20 using Infant Flow (P=0.003). The high flow cannula group had increased oxygen use and more apneas and bradycardias postextubation.\n CPAP delivered by high flow nasal cannula failed to maintain extubation status among preterm infants <or=1,250 g as effectively as Infant Flow CPAP." ]

[ "2071888" ]

[ "Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes." ]

[ "The efficacy and tolerance of orally administered vinpocetine was investigated in patients suffering from mild to moderate organic psychosyndromes including primary dementia. Two hundred and three patients were included in a placebo-controlled, randomized double-blind, multicentre trial and received every day for 16 weeks either: 3 x 10 mg doses of vinpocetine, 3 x 20 mg doses of vinpocetine, or 3 x placebo. Patients were assessed on ratings of clinical global impression, cognitive performance and on measures of the quality of life including depressive illness. There were no clinically relevant side-effects reported and the frequencies of adverse events between patients treated with vinpocetine (30 mg or 60 mg) and placebo were comparable. Statistically significant improvements were found in favour of both active treatment groups compared to placebo in both confirmatory evaluations of efficacy of treatment: the \"Global Improvement\" (on the CGI scale) and cognitive performance (SKT). Vinpocetine was also superior to placebo in ratings of the \"severity of illness\". This study demonstrates the usefulness and efficacy of vinpocetine in the management of patients with moderate organic psychosyndromes. An apparently greater therapeutic efficacy of 3 x 10 mg vinpocetine compared with the higher vinpocetine dosage is statistically not significant." ]

[ "1515246", "7369850", "7880598", "19687168", "17438710", "17468188", "19276838", "16406909", "18972429", "14570527", "6362943", "9597955", "7440831", "19805678" ]

[ "Mastectomy or conservation for early breast cancer: psychological morbidity.", "Psychosocial rehabilitation of gynecologic oncology patients.", "One-year follow-up of the 'Starting Again' group rehabilitation programme for cancer patients.", "Surgery and radioablation therapy combined: introducing a 1-week-condensed procedure bonding total thyroidectomy and radioablation therapy with recombinant human TSH.", "Factors associated with return to work after breast cancer treatment.", "Sick leave for follow-up control in thyroid cancer patients: comparison between stimulation with Thyrogen and thyroid hormone withdrawal.", "A randomized trial to increase physical activity in breast cancer survivors.", "Preoperative biofeedback assisted behavioral training to decrease post-prostatectomy incontinence: a randomized, controlled trial.", "First-year quality of life assessment of an intra-arterial (RADPLAT) versus intravenous chemoradiation phase III trial.", "Improving quality of life in men with prostate cancer: a randomized controlled trial of group education interventions.", "The effect of counselling on physical disability and social recovery after mastectomy.", "Functional outcomes following treatment for advanced laryngeal cancer. Part I--Voice preservation in advanced laryngeal cancer. Part II--Laryngectomy rehabilitation: the state of the art in the VA System. Research Speech-Language Pathologists. Department of Veterans Affairs Laryngeal Cancer Study Group.", "Efficacy of psychosocial intervention with cancer patients.", "Quality of life of patients with endometrial cancer undergoing laparoscopic international federation of gynecology and obstetrics staging compared with laparotomy: a Gynecologic Oncology Group study." ]

[ "A consecutive series of 197 women under 70 years of age with operable breast cancer, randomised to treatment by a conservation technique in comparison to mastectomy, were assessed using structured interviews. The prevalence of cases of anxiety and depression was high before treatment commenced, there were fewer cases in the conservation group but no significant difference at 3 or 12 months in the number of new cases, social adjustment, or capacity to return to work. Attitudes to treatment showed significant differences between the groups, more women in the conservation group were able to wear their usual clothes and most women rated the cosmetic result highly. Patients were more likely to stop sexual intercourse completely after mastectomy. An effective conservation technique should be an attractive treatment choice available to selected women with early breast cancer.", "This investigation studied the effectiveness of in-hospital, individual counseling on the psychosocial adjustment of patients with newly diagnosed gynecologic malignancies. Levels of psychologic distress, sexual functioning, and return to employment were assessed at 3, 6, and 12 months after counseling. The counseled patients were compared with a similar control group that was assessed but not counseled. In this study, levels of psychologic distress reported by cancer patients were similar to those reported in normal populations. However, at 3 months post-treatment, counseled cancer patients reported significantly less confusion and contradiction within areas of self-perception than did the noncounseled patients. Return to employment and sexual activities were both shown to be adversely affected by the diagnosis and treatment of genital cancer. Results suggested that counseling had a positive effect in enhancing return to normal vocational and sexual functions during the 1st year after treatment.", "In a randomised prospective study, a brief structured rehabilitation programme, 'Starting Again', was evaluated over a follow-up year. 98 patients were assigned to the programme, and 101 to the control condition. The 11, 2-h sessions emphasised physical training, information and coping skills. Patients in the programme improved significantly more than the controls with respect to appraisal of having received sufficient information, physical training, physical strength and fighting spirit. Results indicate improvement with respect to the three areas focused on in the 'Starting Again' programme: physical training, information and coping skills training.", "The objective of this study was to determine whether the use of recombinant human TSH (rhTSH) to stimulate radioiodine uptake after thyroidectomy is as efficacious as a period of withholding thyroid hormones, while at the same time avoiding hypothyroidism, reducing sick leave time and shortening the hospital stay.\n Our aim was to compare the standard procedure of differentiated thyroid cancer treatment, which consists of thyroidectomy followed by 4 weeks of hypothyroidism and a conclusive ablative activity of (131)iodine, with a new shortened treatment in which l-thyroxine (T(4)) medication is initiated a day after thyroidectomy, followed by application of rhTSH stimulation and subsequent ablation a few days after surgery. We presumed our treatment to represent the most sophisticated strategy for the reduction in sick leave days overall without any reduction in safety or the efficacy of ablative therapy.\n Patients (n=25) were randomized either for surgery and rhTSH stimulation or surgery and l-T(4) abstinence before the first application of radioiodine. Ablation success was determined by neck ultrasound and serum thyroglobulin during follow-up. RhTSH receivers were monitored for an average of 635 days (s.d.+/-289) and patients in l-T(4) abstinence for an average of 624 days (s.d.+/-205). Both groups were statistically compared for significant differences in treatment efficacy, safety and overall time of sick leave.\n Our shortened treatment proved to be equally efficacious and safe in comparison with the conventional therapy regimen. At the same time, it showed economic advantages through the reduction in average sick leave time from approximately 29 days (l-T(4) abstinence) down to approximately 6 days (rhTSH stimulation) as well as sustaining the patient's quality of life by the complete avoidance of hypothyroidism.", "Relatively few studies have addressed problems regarding return to work after primary treatment for early-stage breast cancer. The purpose of this study was to investigate whether socio-economic and treatment-related factors were associated with problems of returning to work among pre-menopausal women included in a randomized trial of adjuvant endocrine therapy. The duration of all endocrine treatments in the trial was two years. At 24 months after randomization 35 of the 222 recurrence-free patients (16%) had not returned to work. The use of adjuvant endocrine therapy was associated with a twofold increase in the odds ratio of not having returned to work, although the confidence interval of this ratio was wide and included unity. Tumour stage was negatively associated with work status, possibly because of its association with adjuvant chemotherapy and radiotherapy to the regional nodes. Age and investigated social factors (educational level, matrimonial status and presence of under-age children) were not significantly associated with return to work. Determining the significance of other social factors such as vocational motivation, level of income and vocational rehabilitation merits further research.", "The clinical benefits of recombinant human thyroid-stimulating hormone (rhTSH; Thyrogen) are well established as an alternative stimulation procedure to thyroid hormone withdrawal in the diagnostic follow-up of thyroid cancer patients. By avoiding periods of hypothyroidism, patients do not suffer from a decreased quality of life and keep their ability to work. This study compared the frequency, the duration and the cost of sick leave for follow-up control between rhTSH and withdrawal.\n The study population consisted of patients with thyroid carcinoma first treated by thyroidectomy and radioiodine ablation. Patients were recruited at their control visit between October 2004 and May 2006 in three hospitals, both prospectively and retrospectively. Collection data consisted of patient information, job characteristics and duration of sick leave during the month before and the month after control. The valuation of sick leave used the friction cost method.\n Among the 306 patients included, 292 (95%) completed the entire questionnaire. The mean age was 46.7 years. Among the 194 active patients, patients treated with rhTSH, when compared with patients treated by withdrawal, were less likely to require sick leave (11 vs 33%; P=0.001). The mean duration of sick leave was shorter (3.1 vs 11.2 days; P=0.002) and indirect costs due to absenteeism accounted for 454 Euro +/- 1673 vs 1537 Euro +/- 2899 for withdrawal stimulation.\n For active patients, rhTSH treatment reduced the length and the cost of sick leave by 8.1 days and 1083 Euro per control respectively, when compared with withdrawal treatment.", "Interventions to increase physical activity among breast cancer survivors are needed to improve health and quality of life and possibly to reduce the risk of disease recurrence and early mortality. Therefore, we report the feasibility and preliminary outcomes of a pilot randomized trial designed to increase physical activity in sedentary breast cancer survivors receiving hormone therapy.\n Forty-one sedentary women on estrogen receptor modulators or aromatase inhibitors for stage I, II, or IIIA breast cancer were randomly assigned to receive a 12-wk multidisciplinary physical activity behavior change intervention or usual care.\n Recruitment was 34%, intervention adherence was 99%, and complete follow-up data were obtained on 93%. Most participants (93%) were white with mean age of 53 +/- 9 yr. Differences favoring the intervention group were noted for accelerometer physical activity counts (mean difference = 72,103; 95% confidence interval (CI) = 25,383-119,000; effect size (d) = 1.02; P = 0.004), aerobic fitness (mean difference = 2.9; 95% CI = -0.1 to 5.8; d = 0.64; P = 0.058), back/leg muscle strength (mean difference = 12.3; 95% CI = 0.4-15.9; d = 0.81; P = 0.017), waist-to-hip ratio (mean difference = -0.05; 95% CI = -0.01 to -0.08; d = -0.77; P = 0.018), and social well-being (mean difference = 2.0; 95% CI = 0.3-3.8; d = 0.76; P = 0.03). However, the intervention group also reported a greater increase in joint stiffness (mean difference = 1.1; 95% CI = 0.1-2.2; d = 0.70; P = 0.04).\n A behavior change intervention for breast cancer survivors based on the social cognitive theory is feasible and results in potentially meaningful improvements in physical activity and selected health outcomes. Confirmation in a larger study is warranted.", "We tested the effectiveness of preoperative biofeedback assisted behavioral training for decreasing the duration and severity of incontinence, and improving quality of life in the 6 months following radical prostatectomy.\n We performed a prospective, randomized, controlled trial comparing preoperative behavioral training to usual care. The volunteer sample included 125 men 53 to 68 years old who elected radical prostatectomy for prostate cancer. Patients were stratified according to age and tumor differentiation, and randomized to 1 preoperative session of biofeedback assisted behavioral training plus daily home exercise or a usual care control condition, consisting of simple postoperative instructions to interrupt the urinary stream. The main outcome measurements were duration of incontinence (time to continence), as derived from bladder diaries, incontinence severity (the proportion with severe/continual leakage), pad use, Incontinence Impact Questionnaire, psychological distress (Hopkins Symptom Checklist) and health related quality of life (Medical Outcomes Study Short Form Health Survey).\n Preoperative behavioral training significantly decreased time to continence (p = 0.03) and the proportion of patients with severe/continual leakage at the 6-month end point (5.9% vs 19.6%, p = 0.04). There were also significant differences between the groups for self-reported urine loss with coughing (22.0% vs 51.1%, p = 0.003), sneezing (26.0% vs 48.9%, p = 0.02) and getting up from lying down (14.0% vs 31.9%, p = 0.04). No differences were found on return to work and usual activities or quality of life measures.\n Preoperative behavioral training can hasten the recovery of urine control and decrease the severity of incontinence following radical prostatectomy.", "We report the results of a multicenter randomized phase III study, assessing quality of life (QOL) in intra-arterial (IA) versus standard intravenous (IV) chemoradiation in advanced head and neck cancer.\n Two hundred seven patients with inoperable stage IV disease-152 men and 55 women; mean age, 55 years-were included in this study. The patients were treated with standard radiotherapy with 4 weekly IA or 3 weekly IV cisplatin infusions. The QOL assessments carried out were EORTC-C30, H&N35, and trial-specific questionnaires.\n Overall QOL deteriorated in all patients during treatment, is gradually improving over 1 year. IA patients showed significantly less nausea and vomiting at week 7 (p <.001). IV patients were significantly more fatigued (p <.006). At 1 year, no significant difference in tube feeding was found. Voice quality slightly exceeded the pretreatment values at 1 year. Forty-two of 62 employed patients returned to work.\n During treatment, significantly fewer problems with nausea and vomiting occurred in IA than in IV patients. Both groups showed improved voicing and oral intake during follow-up, often exceeding pretreatment values at 1 year.\n (c) 2008 Wiley Periodicals, Inc. Head Neck, 2009.", "Men who were recently treated for prostate cancer (N=250) were randomly assigned to a control group, a group education intervention (GE), or a group education-plus-discussion intervention (GED). Both GE and GED increased prostate cancer knowledge. In the year postintervention, men in the GED condition were less bothered by sexual problems than men in the control condition, and they were more likely to remain steadily employed (93.0%) than men in the GE (75.6%) or control (72.5%) conditions. Among noncollege graduates, GED and GE resulted in better physical functioning than the control condition, and GED resulted in more positive health behaviors than the control or GE condition. Among college graduates, controls were comparable with the GE and GED groups in physical functioning and positive health behaviors.\n 2003 APA, all rights reserved", "A controlled trial was conducted to determine if a specialist nurse improved the physical and social recovery of patients after mastectomy and helped them adapt to the breast loss. Seventy five patients were counselled by the nurse who also monitored their progress after discharge while 77 patients received the care normally given by the surgical unit. Twelve to eighteen months after surgery those helped by the nurse showed a greater social recovery, return to work, adaptation to breast loss and satisfaction with their breast prostheses. Eleven percent remained distressed by the mastectomy but most responded well to breast reconstruction. The nurse had little impact on physical disability. The morbidity found in the control group highlights the need to find ways of reducing it. While the appointment of a specialist nurse can achieve this the morbidity would probably also be much reduced if the breast was conserved when possible, reliable staging methods other than axillary clearance were developed and the adverse effects of cytotoxic drugs and radiotherapy were reduced.", "This two-part investigation assessed functional outcomes related to communication (including amount of speech therapy), swallowing and eating, and employment status for patients who received one of the two treatment modalities for advanced laryngeal cancer (stage III or IV laryngeal squamous cell carcinoma) in Veterans Administration Cooperative Study #268. One hundred sixty-six patients were randomized to primary surgery (laryngectomy) and radiotherapy (RT), and 166 to induction chemotherapy (CT) and RT. The first investigation dealt with examining and comparing functional outcomes for patients in the two treatment arms of the main study. Results showed clearly that patients with advanced laryngeal cancer are better off from the standpoint of speech communication if they can be treated for this disease without removal of the larynx. In contrast, there were few significant differences between patient groups for other non-speech-related measures. The second investigation focused on communication-related outcomes associated with the rehabilitation of total laryngectomy patients. Results revealed that only relatively small percentages of total laryngectomy patients (6%) developed usable esophageal speech or remained nonvocal (8%), and that a majority of patients ended up as users of artificial electrolarynx (55%) or tracheoesophageal (31%) speech. The results from both investigations are discussed with respect to factors that can influence the rehabilitation process and long-term outcome status of patients who are treated for advanced laryngeal cancer with these two strategies.", "nan", "The study's objective was to compare the quality of life (QoL) of patients with endometrial cancer undergoing surgical staging via laparoscopy versus laparotomy.\n The first 802 eligible patients (laparoscopy, n = 535; laparotomy, n = 267) participated in the QoL study in a Gynecologic Oncology Group (GOG) randomized trial of laparoscopy versus laparotomy (GOG 2222). Patients completed QoL assessments at baseline; at 1, 3, and 6 weeks; and at 6 months postsurgery.\n In an intent-to-treat analysis, laparoscopy patients reported significantly higher Functional Assessment of Cancer Therapy-General (FACT-G) scores (P = .001), better physical functioning (P = .006), better body image (BI; P < .001), less pain (P < .001) and its interference with QoL (P < .001), and an earlier resumption of normal activities (P = .003) and return to work (P = .04) over the 6-week postsurgery period, as compared with laparotomy patients. However, the differences in BI and return to work between groups were modest, and the adjusted FACT-G scores did not meet the minimally important difference (MID) between the two surgical arms over 6 weeks. By 6 months, except for better BI in laparoscopy patients (P < .001), the difference in QoL between the two surgical techniques was not statistically significant.\n Although the FACT-G did not show a MID between the two surgical groups, and only modest differences in return to work and BI were found between the two groups, statistically significantly better QoL across many parameters in the laparoscopy arm at 6 weeks provides modest support for the QoL advantage of using laparoscopy to stage patients with early endometrial cancer." ]

[ "9428449", "2557481", "12874466" ]

[ "Correction of metabolic acidosis and its effect on albumin in chronic hemodialysis patients.", "Optimal correction of acidosis changes progression of dialysis osteodystrophy.", "Oral sodium bicarbonate for the treatment of metabolic acidosis in peritoneal dialysis patients: a randomized placebo-control trial." ]

[ "Serum albumin concentration has been strongly associated with risk of death in hemodialysis patients, with mortality increasing as albumin decreases. Metabolic acidosis stimulates protein catabolism and decreases protein synthesis. A study was undertaken to investigate the effect of increasing predialysis serum bicarbonate (HCO3) concentrations on the nutrition of hemodialysis patients as measured by albumin and total lymphocyte count (TLC). Metabolic acidosis was defined as a predialysis serum bicarbonate concentration of < or = 18 mEq/L. Thirty-six hemodialysis patients were enrolled in the study. Each had been stable on hemodialysis for > or = 3 months and each had a mean serum bicarbonate concentration of < or = 18 mEq/L on predialysis monthly laboratory values during the preceding 3 months. The subjects were randomized into 2 groups. The first group consisted of 18 control subjects who were dialyzed on a standard bicarbonate bath of 35 mEq/L. The second group consisted of 18 experimental patients who were dialyzed on a bicarbonate bath of 40 mEq/L. Subjects in the experimental group who had predialysis serum bicarbonate concentrations less than 22 mEq/L after 2 weeks on the higher bicarbonate bath were additionally supplemented with oral sodium bicarbonate at a dosage of 1 mEq/kg dry weight/d. Monthly predialysis laboratory values were checked for all subjects and included serum electrolytes, blood urea nitrogen, calcium, and albumin. TLCs were obtained at the initiation and at the conclusion of the study. Intact parathyroid hormone, blood pressures, and interdialytic weight gains were also followed. The study lasted 16 weeks; 32 subjects completed the study (16 in each group). There were no statistically significant differences between the two groups at the initiation of the study. The serum bicarbonate concentrations were significantly different between the two groups at the end of the study (control HCO3 17.3 +/- 3.2 mEq/L v experimental HCO3 20.2 +/- 2.9 mEq/L; P = 0.01). Serum albumin concentrations and TLCs were not statistically different (P > 0.05) between the two groups at the end of the study (control albumin 3.88 +/- 0.28 g/dL v experimental albumin 3.76 +/- 0.26 g/dL and control TLC 1,780.0 +/- 779.4/mm3 v experimental TLC 2,020.1 +/- 888.0/mm3). Potassium, intact parathyroid hormone, interdialytic weight gain, blood pressures, Kt/Vs, and protein catabolic rates did not differ. We found that the change in serum bicarbonate concentration was well-tolerated and was without any demonstrable side effects. We conclude that increasing the serum bicarbonate concentration by 3 mEq/L for 16 weeks has no effect on the indicators of nutrition that we measured (serum albumin and TLC).", "To investigate an eventual role of acidosis on hemodialysis osteodystrophy we prospectively studied 21 patients who were dialyzed with different amounts of bicarbonate in the dialysate for 18 months. According to the level of bone formation rate (BFR) on a prestudy bone biopsy, patients were split in two subgroups. Inside these two subgroups patients were randomly allocated to two therapeutics groups: 10 patients (group A) were dialyzed with the conventional amount of bicarbonate (33 +/- 2 mmol/liter) in the dialysate; the rest of the patients (group B, N = 11) had 7 to 15 mmol/liter sodium bicarbonate added to the dialysate to obtain 24 mEq predialysis bicarbonate plasma levels. An effective correction of acidosis was shown in group B by a higher predialysis plasma bicarbonate level (15.6 +/- 1 group A vs. 24.0 +/- 0.6 mEq/liter group B, P less than 0.005), which was reached three months after start of the study. Compared to the prestudy bone biopsy, osteoid and osteoblastic surfaces increased in group A but not in group B on the bone biopsies performed at the end of the study. Parathormone plasma level (iPTH), measured with an antiserum which cross reacts with the 44-68 region of PTH molecule, increased during the study in group A but not in group B. This finding suggested progression of secondary hyperparathyroidism (HPT) only in group A patients. Osteocalcin plasma values increased in both groups during the 18 months of the study. Consequently the two subgroups of patients formed on the basis of BFR level were evaluated separately.(ABSTRACT TRUNCATED AT 250 WORDS)", "Acidosis causes malnutrition in peritoneal dialysis (PD) patients. The effect of oral bicarbonate in PD patients with Kt/V <2.1 has not been studied. We randomly assigned 60 PD patients with acidosis and Kt/V <2.1 to oral sodium bicarbonate (0.9 g thrice daily) or placebo. Patients were followed for 12 mo. We compared their nutritional status, including subjective global assessment (SGA) score and normalized protein nitrogen appearance (NPNA), hospitalization and all-cause mortality. Treatment with oral bicarbonate resulted in a higher plasma bicarbonate level at 4 wk (27.8 +/- 2.6 versus 24.7 +/- 3.9 mmol/L, P = 0.002), and the difference persisted until 52 wk. Bicarbonate treatment had a significant effect on the change in overall SGA score (repeated measures ANOVA, P = 0.0003). The overall SGA score of the treatment group was higher than the placebo group at 24 wk (5.07 +/- 0.94 versus 4.40 +/- 1.00, P = 0.015), and the difference persisted thereafter. NPNA rose in the treatment group (1.17 +/- 0.32 to 1.28 +/- 0.26 g/kg per d, P = 0.034), but declined in placebo group (1.13 +/- 0.25 to 1.03 +/- 0.28 g/kg per d, P = 0.054). The treatment group had a shorter hospitalization than the placebo group (8.4 +/- 17.7 versus 16.8 +/- 21.7 d/yr; P = 0.02). Mortality was not significantly different. Although our trial has limited statistical power, we find that in PD patients with mild acidosis and Kt/V <2.1, oral sodium bicarbonate probably improve nutritional status and reduce the duration of hospitalization." ]

[ "7117676", "2756515", "6504709" ]

[ "Experience with once-daily and twice-daily slow-release frusemide in hypertension.", "[Efficacy and tolerability of cycletanine in aged patients with hypertension].", "Antihypertensive and biochemical effects of indacrinone enantiomers." ]

[ "Out of thirty-six patients with mild to moderate hypertension twenty-six patients completed a double-blind comparison of slow-release frusemide at two dose levels, and placebo. The two groups differed in their age pattern, baseline level of blood pressure and response to a low-salt diet during the wash-out/run-in period. Despite the lack of comparability of the two groups, firm clinical inferences could be drawn from the study. Seven of the eighteen placebo patients had to be withdrawn from further participation because of deterioration in their hypertension: in contrast, fifteen of the eighteen frusemide patients showed an anti-hypertensive response and none was withdrawn because of lack of effect. Twice-daily administration of the slow-release formulation, however, produced an unacceptable level of such side-effects as nocturia, nausea and vomiting. Once-daily administration of the preparation is therefore preferred.", "Moderate arterial hypertension of the elderly has to be treated but the efficacy has to be progressive. Cicletanine has a pharmacokinetic profile well fitted to the therapy of this age group. The mechanism of action is characterized by synthesis of prostacyclin. A double blind prospective randomized study was conducted at two institutions on 132 patients aged more than 60, with diastolic arterial pressure over 95 mmHg and systolic over 160 mmHg. 62.9% of them were aged more than 75. The analysis of those two studies shows that the three groups with cicletanine (respectively 50, 100 and 150 mg per day) had a significant decrease of both pressures versus placebo. In the 50 mg group, 40% of arterial pressures were normalized after 3 months of treatment. There were no difference between 50 and 100 mg. There were no adverse drug reaction like falling down, day or night, or orthostatic hypotension. The biological tolerance, more particularly renal, was excellent with this dose of 50 mg a day. Cicletanine at the dose of 50 mg/day is a recommended treatment in arterial hypertension of the elderly.", "The enantiomers of indacrinone (I), an investigational loop diuretic, have different pharmacologic activity. The (-) enantiomer is natriuretic, and the (+) enantiomer is uricosuric. To determine the antihypertensive effects and an isouricemic ratio of indacrinone enantiomers, 37 patients with sitting diastolic blood pressure (BP) between 90 and 104 mm Hg, after a 4-week placebo washout, randomly received one of the ratios of I enantiomers, namely -2.5/+80 mg (A), -5/+80 mg (B), -10/+80 mg (C) or placebo (P), once daily for 12 weeks in a double-blind, parallel study. The mean reductions (baseline-end of treatment) in BP of 23/8, 20/10 and 25/10 mm Hg with treatments A, B and C respectively were greater (p less than 0.01) than that on P (0/3). Initially, serum uric acid decreased with treatments A and B but not with C. Mean changes in serum uric acid were -0.3, -0.4, 0.2 and 0.3 mg/dl respectively with treatments A, B, C and P. The ratio of -10/+80 mg produced least variation in serum uric acid. Reduction in serum K+ and Cl- appeared to be dose related to (-) enantiomer. No serious adverse effects were reported. A 1:9 ratio of I enantiomers intended for wide-scale use as a diuretic also showed good antihypertensive activity, a favorable uric acid profile and absence of hepatic toxicity in 14 patients." ]