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[ "15611808" ]

[ "The Canadian Optimal Therapy of COPD Trial: design, organization and patient recruitment." ]

[ "There are no published studies that have assessed whether adding long-acting beta 2-agonist bronchodilators and/or inhaled steroids to chronic therapy with tiotropium would provide additional clinical benefit to patients with moderate to severe chronic obstructive pulmonary disease (COPD).\n The Canadian Optimal Therapy of COPD Trial is a randomized, prospective, double-blind, placebo-controlled, multicentre trial funded by the Canadian Institutes of Health Research that has been designed to determine which combination of inhaled medications will most effectively prevent exacerbations and optimize disease-specific quality of life in patients with COPD. The trial is the first to evolve from the Canadian Thoracic Society Clinical Trials Group. The study will randomize 432 patients with moderate to severe COPD to one of three parallel treatment arms for 52 weeks: tiotropium and fluticasone/salmeterol; tiotropium and salmeterol; or tiotropium and placebo inhaler. The participants will be allowed to use salbutamol as required throughout the trial period.\n The primary outcome measure is the proportion of patients in the three treatment groups who experienced a respiratory exacerbation within 52 weeks of randomization. Other outcomes that will be assessed over the 52-week trial period will include: changes in disease-specific quality of life and changes in dyspnea, health care use and changes in lung function. A pharmacoeconomic analysis will also be performed to evaluate the cost of these therapies.\n The study commenced recruitment in October 2003. It is currently operating at 22 centres across Canada and has randomized 137 patients during the first four months of recruitment. Recruitment is scheduled to continue until April 2005 or until 432 patients have been randomized.\n The present randomized, placebo-controlled trial offers a unique opportunity to answer the question, what is the best combination of inhaled medications to use for COPD patients? It is hoped that optimal use of inhaled medications will improve patient health and quality of life, reduce patient respiratory exacerbations, and ultimately, reduce health care resource use." ]

[ "10489026", "8301153", "10102427", "8469318", "12926838", "8145906", "8602746", "9820297" ]

[ "Evidence of interferon beta-1a dose response in relapsing-remitting MS: the OWIMS Study. The Once Weekly Interferon for MS Study Group.", "Systemic recombinant human interferon-beta treatment of relapsing-remitting multiple sclerosis: pilot study analysis and six-year follow-up.", "Interferon-alpha2a reduces MRI disease activity in relapsing-remitting multiple sclerosis. Norwegian Study Group on Interferon-alpha in Multiple Sclerosis.", "Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group.", "Oral interferon beta-1a in relapsing-remitting multiple sclerosis: a double-blind randomized study.", "Chronic systemic high-dose recombinant interferon alfa-2a reduces exacerbation rate, MRI signs of disease activity, and lymphocyte interferon gamma production in relapsing-remitting multiple sclerosis.", "Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG)", "Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group." ]

[ "To compare efficacy of interferon beta-1a, 22 microg or 44 microg weekly, with placebo in relapsing MS.\n Uncertainty exists concerning the optimal dose regimen for interferon beta in relapsing-remitting MS. Many patients and physicians prefer the convenience and lesser side effects of an injection given once weekly (qw) as opposed to three times weekly. Pharmacokinetic data and information on biologic markers suggest that this frequency may be suboptimal.\n Randomized, double-blind study of interferon beta-1a 22 microg, 44 microg, or placebo administered by weekly subcutaneous injection for 48 weeks. Proton density (PD)/T2-weighted and T1-weighted-gadolinium MRI scans during 24 weeks of therapy were analyzed for the number of combined unique (CU) lesions (primary outcome). Biannual PD/T2 scans were analyzed for T2 activity and burden of disease (BOD).\n CU lesions at 24 weeks had a median of 0.71/scan with placebo, 0.5/scan with 22 microg (not significant), and 0.33/scan with 44 microg (p = 0.002). T2 new lesion count/scan (mean/median) at 48 weeks was 3.2/1.5 for placebo, 2.4/1.0 for 22 microg (p = 0.03), and 1.5/1.0 for 44 microg (p = 0.0005). BOD at 48 weeks showed a median increase of 5.9% for placebo compared with a decrease of 1.4% in the 44 microg group (p = 0.0058) and 2% in the 22 microg group (p = 0.0018). No clinical variable, apart from steroid use in the 44 microg qw group (p = 0.014), showed significance.\n These data confirm an MRI benefit of interferon beta-1a at low dose in MS, but highlight the limited clinical effect. Taken together with other studies, the data demonstrate a dose-effect relationship for both clinical and MRI variables.", "A pilot study was undertaken to test the safety and establish the side effect profile of recombinant human interferon-beta 1b (Betaseron, Berlex Laboratories, Richmond, CA), in patients with relapsing-remitting multiple sclerosis (RRMS). During the initial dose finding period (24 weeks), five groups of 6 patients each were treated by subcutaneous injection three times each week with either 0.8, 4, 8, or 16 million units (mU) of Betaseron or placebo (WHO Standard). Although some side effects were noted in all groups, a dose-related trend in reduction of exacerbation frequency and side-effect profile was noted. Patients given 16 mU had no exacerbations during the initial dosing period, but associated side effects led to dose reduction or dropout. An 8 mU dose was selected for further study after 24 weeks, and continuous dosing at 8 mU in 15 patients has now exceeded 6 years. Side effects abated over time. Neutralizing antibody developed in most patients, but titers were variable, fluctuated independently of clinical course, and tended to fall with prolonged treatment. A dose-dependent rise in neopterin levels was observed during the initial dosing period. This pilot study has demonstrated responsiveness to Betaseron, shown a stable safety profile over time, and established guidelines for a dosing regimen to evaluate and optimize further the efficacy of Betaseron in RRMS.", "To evaluate the efficacy and safety of interferon-alpha2a (IFN-alpha2a) in relapsing-remitting MS (RRMS).\n Several immune-modulating therapy regimens of IFN-alpha have shown varying results in MS. A recent pilot study suggested benefits from IFN-alpha2a.\n Ninety-seven patients were randomized to receive subcutaneous injections of placebo (33 patients) or 4.5 million international units (mIU) (32 patients) or 9.0 mIU (32 patients) of IFN-alpha2a three times weekly for 6 months, with a further 6 months of follow-up. Monthly gadodiamide-enhanced MRI was the primary method of evaluating efficacy.\n IFN-alpha2a treatment resulted in fewer new MRI lesions during the treatment period (p < 0.003). The probability of no new lesions during treatment was >2.5 times higher with 9.0 mIU IFN-alpha2a than with placebo (p < 0.005). The median number of lesions at the end of treatment was lower with IFN-alpha2a treatment than with placebo (p = 0.0004), but the difference disappeared during follow-up. The total number of lesions (mean) increased by 4.78 with placebo, 0.86 with 4.5 mIU IFN-alpha2a, and 0.28 with 9.0 mIU IFN-alpha2a during treatment (p = 0.030). No treatment effect on exacerbation rate, progression of disability, or quality of life was detected. Nine patients discontinued treatment, five because of adverse events.\n IFN-alpha2a treatment significantly reduced disease activity as measured by MRI, but the efficacy disappeared within 6 months after discontinuation of treatment. A long-term study of more patients using disability as a primary outcome measure is needed to evaluate the clinical impact.", "We report a multicenter, randomized, double-blind, placebo-controlled trial of interferon beta-1b (IFNB) in 372 ambulatory patients with relapsing-remitting multiple sclerosis (MS). Entry criteria included an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 and at least two exacerbations in the previous 2 years. One-third of the patients received placebo, one-third 1.6 million international units (MIU) of IFNB, and one-third 8 MIU of IFNB, self-administered by subcutaneous injections every other day. The primary end points were differences in exacerbation rates and proportion of patients remaining exacerbation-free. The annual exacerbation rate for patients receiving placebo was 1.27; for 1.6 MIU IFNB, 1.17; and for 8 MIU IFNB, 0.84 after 2 years. Exacerbation rates were significantly lower in both treatment groups compared with the placebo group (8 MIU versus placebo, p = 0.0001; 1.6 MIU versus placebo, p = 0.0101; and 8 MIU versus 1.6 MIU, p = 0.0086), suggesting a dosage effect. The reduction in exacerbation severity in the 8 MIU group was attributable to a twofold reduction in the frequency of moderate and severe attacks. More patients in the 8 MIU group (n = 36) were exacerbation-free at 2 years compared with the placebo group (n = 18; p = 0.007). EDSS scores changed little from baseline in both the placebo and treatment arms. Accordingly, a significant change in disability could not be discerned in this trial. Finally, in serial MRIs, MS activity was significantly less in the high-dose IFNB group.(ABSTRACT TRUNCATED AT 250 WORDS)", "Interferon beta (IFNB) is available in parenteral formulations for treatment of multiple sclerosis (MS). The purpose of this study was to evaluate safety, tolerability and effects on MRI lesions of three different doses of oral IFNB-1a compared with placebo over six months in relapsing-remitting (RR) MS patients.\n In this multicenter; double-blind randomized trial, RR-MS patients received 0.06, 0.6 or 6 million international units (MIU) IFNB-1a or placebo every other day for up to six months. Gadolinium DTPA-enhanced brain MRI scans were performed at screening and monthly during treatment. The primary variable was the cumulative number of newly active lesions. Secondary variables included volume of enhancing lesions on T1-weighted images each month and lesion volume on T2-weighted images at months three and six. Safety measures included adverse events, laboratory variables, vital signs, ECG, physical examination, EDSS and number of relapses. Neopterin was measured in 21 patients and neutralizing antibodies in 24 patients.\n Of 194 screened patients, 173 were randomized (42-44 patients per group) in 15 centers. Median cumulative numbers of newly active lesions over six months were 4.0 in the placebo and 0.6 MIU groups, compared with 7.5 and 9.0 in the 0.06 and 6 MIU groups (no significant differences). Secondary efficacy endpoints showed small and inconsistent differences between groups. Adverse events showed no notable group differences. Approximately two-thirds of patients in each group remained relapse free. No patients showed neutralizing antibodies. Neopterin levels were comparable between groups.\n Oral IFNB-1a showed neither beneficial effects in RRMS nor any systemic biological effects. Treatment was safe and well tolerated.", "We report a randomized, double-blind, placebo-controlled pilot trial of systemic high-dose recombinant interferon alfa-2a (rIFNA) in 20 patients with relapsing-remitting (RR) multiple sclerosis (MS). Patients received 9 million IU rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions on serial MRI occurred in two of 12 rIFNA-treated and in seven of eight placebo-treated patients (p < 0.005). There was only one enlarging MRI lesion in the rIFNA group, whereas 27 new or enlarging lesions were present in the placebo group (p < 0.01). Baseline lymphocyte interferon gamma production of 19.10 +/- 7.12 IU/ml significantly decreased to 3.03 +/- 0.66 IU/ml (p < 0.04) in the rIFNA group, whereas production was unchanged in the placebo group. The rIFNA was tolerated without dropouts or serious side effects, but fever, malaise, fatigue (interfering with daily activities in two patients), and leukopenia occurred frequently. Neuropsychological tests excluded neurotoxicity. High-dose systemic rIFNA might reduce clinical and MRI signs of disease activity in RR MS and should be investigated in larger trials.", "The accepted standard treatment of relapsing multiple sclerosis consists of medications for disease symptoms, including treatment for acute exacerbations. However, currently there is no therapy that alters the progression of physical disability associated with this disease. The purpose of this study was to determine whether interferon beta-1a could slow the progressive, irreversible, neurological disability of relapsing multiple sclerosis. Three hundred one patients with relapsing multiple sclerosis were randomized into a double-blinded, placebo-controlled, multicenter phase III trial of interferon beta-1a. Interferon beta-1a, 6.0 million units (30 micrograms¿, was administered by intramuscular injection weekly. The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Expanded Disability Status Scale (EDSS). Interferon beta-1a treatment produced a significant delay in time to sustained EDSS progression (p = 0.02). The Kaplan-Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9% in the placebo group and 21.9% in the interferon beta-1a-treated group. Patients treated with interferon beta-1a also had significantly fewer exacerbations (p = 0.03) and a significantly lower number and volume of gadolinium-enhanced brain lesions on magnetic resonance images (p-values ranging between 0.02 and 0.05). Over 2 years, the annual exacerbation rate was 0.90 in placebo-treated patients versus 0.61 in interferon beta-1a-treated patients. There were no major adverse events related to treatment. Interferon beta-1a had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium-enhanced lesions on brain magnetic resonance images. This treatment may alter the fundamental course of relapsing multiple sclerosis.", "Previous trials of interferon beta in multiple sclerosis (MS) have shown efficacy, but the degree of clinical benefit remains uncertain, and the optimum dose is not known. We undertook a double-blind, placebo-controlled study in relapsing/remitting MS to investigate the effects of subcutaneous interferon beta-1a.\n 560 patients with Kurtzke expanded disability status scale (EDSS) scores of 0-5.0, from 22 centres in nine countries, were randomly assigned subcutaneous recombinant interferon beta-1a 22 microg (n=189), or 44 microg (n=184), or placebo (n=187) three times a week for 2 years. Neurological examinations were done every 3 months. All patients had MRI twice yearly and 205 had monthly scans in the first 9 months of treatment. Analysis was by intention to treat.\n Clinical data on 533 (95%) patients were available at 2 years. The relapse rate was significantly lower at 1 and 2 years with both doses of interferon beta-1a than with placebo (mean number per patient 1.82 for 22 microg group, 1.73 for 44 microg group vs 2.56 for placebo group: risk reductions 27% [95% CI 14-39] and 33 [21-44]). Time to first relapse was prolonged by 3 and 5 months in the 22 microg and 44 microg groups respectively, and the proportion of relapse-free patients was significantly increased (p<0.05). Interferon beta-1a delayed progression in disability, and decreased accumulated disability during the study. The accumulation of burden of disease and number of active lesions on MRI was lower in both treatment groups than in the placebo group.\n Subcutaneous interferon beta-1a is an effective treatment for relapsing/remitting MS in terms of relapse rate, defined disability, and all MRI outcome measures in a dose-related manner, and it is well tolerated. Longer-term benefits may become clearer with further follow-up and investigation." ]

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[ "Inhalation aromatherapy during radiotherapy: results of a placebo-controlled double-blind randomized trial.", "Effects of music therapy on physiological and psychological outcomes for patients undergoing cardiac surgery.", "Preventing falls on an elderly care rehabilitation ward.", "Bacteriological observations in a mechanically ventilated experimental ward and in two open-plan wards.", "The effect of music listening on older adults undergoing cardiovascular surgery.", "Music versus distraction for procedural pain and anxiety in patients with cancer.", "The effect of an auditory distraction on anxiety in ambulatory surgical patients experiencing regional anesthesia.", "Effects of music therapy on women's physiologic measures, anxiety, and satisfaction during cesarean delivery.", "A music intervention to reduce anxiety before vascular angiography procedures.", "Stress reduction through music in patients undergoing cerebral angiography.", "Listening to music decreases need for sedative medication during colonoscopy: a randomized, controlled trial.", "Nasal acquisition of Staphylococcus aureus in partly divided wards.", "The effect of sunlight on postoperative analgesic medication use: a prospective study of patients undergoing spinal surgery.", "Music does not reduce alfentanil requirement during patient-controlled analgesia (PCA) use in extracorporeal shock wave lithotripsy for renal stones.", "Effects of music on patients undergoing a C-clamp procedure after percutaneous coronary interventions.", "Distraction therapy with nature sights and sounds reduces pain during flexible bronchoscopy: a complementary approach to routine analgesia.", "The use of music to reduce anxiety for patients undergoing colposcopy: a randomized trial.", "Impact of portable air filtration units on exposure of haematology-oncology patients to airborne Aspergillus fumigatus spores under field conditions.", "Psychophysiologic responses of mechanically ventilated patients to music: a pilot study.", "Music as an adjunct to antiemetic therapy.", "Relaxing intraoperative natural sound blunts haemodynamic change at the emergence from propofol general anaesthesia and increases the acceptability of anaesthesia to the patient.", "Effect of music on vital signs and postoperative pain.", "The effect of self-selected music during colonoscopy on anxiety, heart rate, and blood pressure.", "The effects of music on cardiac patients on bed rest.", "Effect of music therapy in the postanesthesia care unit: a nursing intervention.", "The effect of humorous and musical distraction on preoperative anxiety.", "The effect of humorous distraction on preoperative anxiety. A pilot study.", "Relaxation techniques for reducing pain and anxiety during screening mammography.", "Music for postoperative pain and anxiety.", "Analgesia following music and therapeutic suggestions in the PACU in ambulatory surgery; a randomized controlled trial.", "Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study.", "[Reduction of preoperative anxiety. A study comparing music, Thalamonal and no premedication].", "[The effect of music therapy on anxiety level in hospitalized asthmatic patients].", "Music and ambient operating room noise in patients undergoing spinal anesthesia.", "Effects of music in patients who had chronic cancer pain.", "Epidural versus general anesthesia, ambient operating room temperature, and patient age as predictors of inadvertent hypothermia.", "[\"Walkman music\" during epidural anesthesia].", "Effect of music therapy on state anxiety in patients undergoing flexible sigmoidoscopy.", "Taped therapeutic suggestions and taped music as adjuncts in the care of coronary-artery-bypass patients.", "Using massage and music therapy to improve postoperative outcomes.", "Normalization of hypertensive responses during ambulatory surgical stress by perioperative music.", "Music during bronchoscopic examination: the physiological effects. A randomized trial.", "Burn pain and anxiety: the use of music relaxation during rehabilitation.", "Effect of environmental surroundings on outpatients' mood and perception of psychiatrists.", "Effects of patient-controlled music therapy during coronary angiography on procedural pain and anxiety distress syndrome.", "The effect of music on the neurohormonal stress response to surgery under general anesthesia.", "The effect of music on preoperative sedation and the bispectral index.", "Stress reduction through listening to Indian classical music during gastroscopy.", "Comparative randomized study of protected environment plus oral antibiotics versus oral antibiotics alone in neutropenic patients.", "Effects of music on patient anxiety in coronary care units.", "Music reduces stress and anxiety of patients in the surgical holding area.", "The effect of a vinyl floor surface and a carpeted floor surface upon walking in elderly hospital in-patients.", "Effect of music on state anxiety scores in patients undergoing fiberoptic bronchoscopy.", "A music intervention to reduce anxiety prior to gastrointestinal procedures.", "A randomized, controlled trial of the use of music during laceration repair.", "Audio and visual stimulation reduces patient discomfort during screening flexible sigmoidoscopy.", "The effect of nursing interventions utilizing music therapy or sensory information on Chinese patients' anxiety prior to cardiac catheterization: a pilot study.", "Music decreases sedative requirements during spinal anesthesia.", "Effects of relaxing music on cardiac autonomic balance and anxiety after acute myocardial infarction.", "Music reduces sensation and distress of labor pain.", "Reclining chairs reduce pain from gurneys in older emergency department patients: a randomized controlled trial.", "Music and its effect on the physiological responses and anxiety levels of patients receiving mechanical ventilation: a pilot study.", "Music as a therapeutic intervention for anxiety in patients receiving radiation therapy.", "Relaxation music decreases the dose of patient-controlled sedation during colonoscopy: a prospective randomized controlled trial.", "Music: an intervention for pain during chest tube removal after open heart surgery.", "Effects of a single music therapy intervention on anxiety, discomfort, satisfaction, and compliance with screening guidelines in outpatients undergoing flexible sigmoidoscopy.", "Improved recovery after music and therapeutic suggestions during general anaesthesia: a double-blind randomised controlled trial.", "The sedative and analgesic sparing effect of music.", "Music increases satisfaction in elderly outpatients undergoing cataract surgery.", "Improved procedure of colonoscopy under accompanying music therapy.", "Hemispheric-synchronisation during anaesthesia: a double-blind randomised trial using audiotapes for intra-operative nociception control.", "Sedative music reduces anxiety and pain during chair rest after open-heart surgery.", "The effect of music in the postanesthesia care unit on pain levels in women who have had abdominal hysterectomies.", "Effects of music on target-controlled infusion of propofol requirements during combined spinal-epidural anaesthesia.", "Effects of different interior decorations in the seclusion area of a psychiatric acute ward.", "Anxiety during the performance of colonoscopies: modification using music therapy.", "Relaxation response in femoral angiography.", "The effect of music on preoperative anxiety in day surgery.", "Stress reduction and analgesia in patients exposed to calming music postoperatively: a randomized controlled trial.", "Can visual distraction decrease the dose of patient-controlled sedation required during colonoscopy? A prospective randomized controlled trial.", "A prospective, randomised, controlled study examining binaural beat audio and pre-operative anxiety in patients undergoing general anaesthesia for day case surgery.", "Physiologic responses of coronary care patients to selected music." ]

[ "To determine whether the inhalation of aromatherapy during radiotherapy reduces anxiety.\n Three hundred thirteen patients undergoing radiotherapy were randomly assigned to receive either carrier oil with fractionated oils, carrier oil only, or pure essential oils of lavender, bergamot, and cedarwood administered by inhalation concurrently with radiation treatment. Patients underwent assessment by the Hospital Anxiety and Depression Scale (HADS) and the Somatic and Psychological Health Report (SPHERE) at baseline and at treatment completion.\n There were no significant differences in HADS depression or SPHERE scores between the randomly assigned groups. However, HADS anxiety scores were significantly lower at treatment completion in the carrier oil only group compared with either of the fragrant arms (P =.04).\n Aromatherapy, as administered in this study, is not beneficial.", "Cardiac surgery is a common interventional procedure for ischemic and valvular heart disease. Cardiac surgery is accompanied by postoperative pain and anxiety. The use of music therapy has been shown to reduce pain, anxiety, and physiological parameters in patients having surgical procedures.\n To compare the effects of music therapy versus a quiet, uninterrupted rest period on pain intensity, anxiety, physiological parameters, and opioid consumption after cardiac surgery.\n An experimental design was used. A total sample of 86 patients (69.8% males) were randomized to 1 of 2 groups; 50 patients received 20 minutes of music (intervention), whereas 36 patients had 20 minutes of rest in bed (control). Anxiety, pain, physiologic parameters, and opioid consumption were measured before and after the 20-minute period.\n A significant reduction in anxiety (P < or = .001) and pain (P = .009) was demonstrated in the group that received music compared with the control group, but no difference was observed in systolic blood pressure (P = .17), diastolic blood pressure (P = .11), or heart rate (P = .76). There was no reduction in opioid usage in the 2 groups.\n Patients recovering from cardiac surgery may benefit from music therapy.", "Comparison of two flooring types--carpet and vinyl--in the bed areas, and two modes of physiotherapy--conventional therapy and additional leg strengthening exercises--in avoiding falls.\n Randomized 2 x 2 controlled trial.\n Elderly care rehabilitation ward in a community hospital.\n Fifty-four consecutive patients referred for rehabilitation.\n The incidence of falls, and the change in strength.\n There were 10 falls on carpet, and only a single fall on vinyl floor covering (relative risk 8.3, 95% confidence interval 0.95-73, p = 0.05). There were four falls in those receiving additional exercise, and seven falls in those receiving only conventional physiotherapy (relative risk 0.21, 95% confidence interval 0.04-1.2, p = 0.12). Fifty-nine per cent of patients were able to complete strength measurements on admission and discharge. In these, handgrip strength improved more in those given additional exercise than conventional physiotherapy (2.1 kg versus -0.3 kg, p < 0.05).\n There is no evidence to support either intervention in preventing falls on a rehabilitation ward, but within this low-powered study, there was a strong trend towards vinyl being superior.", "nan", "The purpose of this study was to determine the effect of music listening on postoperative anxiety and intubation time in patients undergoing cardiovascular surgery. Coronary artery disease and valvular heart disease affect approximately 15 million Americans and 5 million persons in the U.K. annually, with the majority of these patients being older adults. The anxiety experienced before, during and after surgery increases cardiovascular workload, thereby prolonging recovery time. Music listening as a nursing intervention has shown an ability to reduce anxiety. The study used a randomized control trial design. Sixty adults older than 65 years were randomly assigned to the control and the experimental groups. The experimental group listened to music during and after surgery, while the control group received standard postoperative care. The Spielberger State Trait Anxiety Inventory was administered to both groups before surgery and 3 days postoperatively. The mean of the differences between scores was compared using analysis of variance. Differences in mean intubation time were measured in both groups. Older adults who listened to music had lower scores on the state anxiety test (F = 5.57, p = .022) and had significantly fewer minutes of postoperative intubation (F = 5.45, p = .031) after cardiovascular surgery. Older adults undergoing cardiovascular surgery who listen to music had less anxiety and reduced intubation time than those who did not.", "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.", "nan", "The purpose of the study was to investigate the effects of music therapy on women's physiologic measures, level of anxiety, and satisfaction during cesarean delivery. Sixty-four women who were planning to have a cesarean delivery were randomly divided into an experimental and a control group. The experimental group received routine care and music therapy, whereas the control group received routine care only. Our results indicated that compared to the control group the experimental group had significantly lower anxiety and a higher level of satisfaction regarding the cesarean experience. No significant differences were found between the two groups in any of the physiological indexes. This controlled study provides evidence that music therapy can reduce anxiety and create a more satisfying experience for women undergoing cesarean delivery.", "Patients scheduled for vascular angiography are often anxious and frightened. High levels of anxiety may result in more difficult and painful procedures. Past research has reported mixed results for anxiety reduction techniques in other procedures settings, such as education, cognitive-behavioral skills, coping and relaxation skills, combinations of techniques, and music. Music as an intervention for pre-procedural anxiety prior to vascular angiography has not been studied. A randomized controlled trial of 170 patients was undertaken to determine whether 15 minutes of self-selected music reduced pre-procedure anxiety. The State Trait Anxiety Inventory was used to measure patients' anxiety. One-hundred sixty-six men and 4 women comprised the sample with an average age of 66.8 years (SD 9.95, range 37 to 85 years). Patients who listened to music (n=89) reduced their anxiety score from 38.57 (SD 10.46) to 35.2 (SD 9.7), while those who did not listen to music (n=81) reduced their anxiety score from 36.23 (SD 10.54) to 35.1 (SD 10.59); the difference between the groups was statistically significant (t=1.95, df 161, p=0.05). Pulse achieved a statistically significant reduction in the music group (t=2.45, df 167, p=0.02). Music is a noninvasive nursing intervention that patients enjoy and reduces their anxiety and their pulse rate. Further research should address using music to reduce anxiety in other interventional vascular angiography settings with equal numbers of men and women and comparing self-selected versus investigator-selected music.", "We studied the influence of music on stress reaction of patients during cerebral angiography. We randomised 30 patients to a music or a control group. We measured stress hormones, blood pressure, heart rate and psychological parameters. Patients examined without music showed rising levels of cortisol in plasma, indicating high stress levels, while cortisol in patients examined with music remained stable. Systolic blood pressure was significantly lower listening to music. Patients with a high level of fear did appear to benefit particularly from the music.", "Music played during endoscopic procedures may alleviate anxiety and improve patient acceptance of the procedure. A prospective randomized, controlled trial was undertaken to determine whether music decreases the requirement for midazolam during colonoscopy and makes the procedure more comfortable and acceptable.\n Patients undergoing elective colonoscopy between October 2003 and February 2004 were randomized to either not listen to music (Group 1; n=40) or listen to music of their choice (Group 2; n=38) during the procedure. All patients received intravenous midazolam on demand in aliquots of 2 mg each. The dose of midazolam, duration of procedure, recovery time, pain and discomfort scores and willingness to undergo a repeat procedure using the same sedation protocol were compared.\n Patients in Group 2 received significantly less midazolam than those in Group 1 (p=0.007). The pain score was similar in the two groups, whereas discomfort score was lower in Group 2 (p=0.001). Patients in the two groups were equally likely to be willing for a repeat procedure.\n Listening to music during colonoscopy helps reduce the dose of sedative medications and decreases discomfort experienced during the procedure.", "The spread of coagulase-positive staphylococci has been studied in a modern hospital in which most of the patients were nursed in 4-bed rooms separated from a common corridor only by low dividing walls. Acquisition of new nasal strains from patients in other bedrooms was nearly as easy as from patients in the neighbouring beds. There was no indication that subdivision of this type hindered the spread of nasal strains as compared with open wards of the ;Nightingale' pattern.", "Exposure to natural sunlight has been associated with improvement in mood, reduced mortality among patients with cancer, and reduced length of hospitalization for patients who have experienced myocardial infarction. Our aim was to evaluate whether the amount of sunlight in a hospital room modifies a patient's psychosocial health, the quantity of analgesic medication used, and the pain medication cost.\n A prospective study of pain medication use was conducted in 89 patients undergoing elective cervical and lumbar spinal surgery where they were housed on either the \"bright\" or \"dim\" side of the same hospital unit. Analgesic medication was converted to standard morphine equivalents for interpatient comparison. The intensity of sunlight in each hospital room was measured daily and psychologic questionnaires were administered on the day after surgery and at discharge.\n Patients staying on the bright side of the hospital unit were exposed to 46% higher-intensity sunlight on average (p = .005). Patients exposed to an increased intensity of sunlight experienced less perceived stress (p = .035), marginally less pain (p = .058), took 22% less analgesic medication per hour (p = .047), and had 21% less pain medication costs (p = .047). Age quartile was the only other variable found to be a predictor of analgesic use, with a significant negative correlation (p <.001). However, patients housed on the bright side of the hospital consistently used less analgesic medications in all age quartiles.\n The exposure postoperatively of patients who have undergone spinal surgery to increased amounts of natural sunlight during their hospital recovery period may result in decreased stress, pain, analgesic medication use, and pain medication costs.", "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.", "This paper reports a study to determine the effect of music on physiological parameters and level of pain in patients undergoing application of a C-clamp after percutaneous coronary interventions.\n Most percutaneous coronary interventions are performed through the femoral artery. In order to stop bleeding and achieve homeostasis, a C-clamp is used after percutaneous coronary interventions. However, the experience is painful for patients and they inevitably suffer discomfort. Pain may lead to stress responses and may affect the physical and mental health of patients. One potential beneficial practice is having the patient listen to relaxing music, which might have the effect of reducing situational discomfort and pain.\n A randomized controlled study was conducted during the period September 2004 to March 2005. Forty-three people (20 experimental and 23 control) were recruited from the intensive care units of two acute care hospitals in Hong Kong. Physiological and psychological variables were collected at baseline and at 15, 30 and 45 minutes.\n In the music group, there were statistically significant reductions (P=0.001) in heart rate, respiratory rate, and oxygen saturation than the control participants at 45 minutes. In the music group, statistically significant reductions (P=0.001) in systolic blood pressure, heart rate, respiratory rate and oxygen saturation were found at the four time points, but not in the control group. No statistically significant differences were found at baseline comparison of the two groups, but statistically significant differences in pain scores were found at 45 minutes for participants in the music group compared with the control group (P=0.003). Participants in the control group showed statistically significant increases in pain at 45 minutes compared with baseline (P<0.001).\n The benefits of preventing physiological reactions to pain were demonstrated. Music is a simple, safe and effective method of reducing potentially harmful physiological and psychological responses arising from pain.", "To determine whether distraction therapy with nature sights and sounds during flexible bronchoscopy (FB) reduces pain and anxiety.\n Randomized controlled trial.\n Teaching hospital in Baltimore, MD.\n Consecutive adult patients (n = 80) undergoing FB with conscious sedation.\n Nature scene murals were placed at the bedside, and patients were provided a tape of nature sounds to listen to before, during, and after the procedure. Patients assigned to the control group were not offered either the nature scene or the sounds. Measurements and results: The primary outcomes were patient ratings of pain control (a 5-point scale ranging from poor to excellent) and anxiety. In a multivariate ordinal logistic regression model, the odds of better pain control were greater in the intervention patients than in the control patients (odds ratio [OR], 4.76; 95% confidence interval [CI], 1.35 to 16.7), after adjustment for age, gender, race, education, health status, and dose of narcotic medication. Older patients and patients with better health status reported significantly less pain. There was no difference in patient-reported anxiety between the two groups (OR, 0.87; 95% CI, 0.39 to 1.96).\n Distraction therapy with nature sights and sounds significantly reduces pain in patients undergoing FB. Although the precise mechanism of this beneficial effect requires further investigation, clinicians should consider this nonintrusive strategy in addition to standard analgesic medications in patients undergoing painful, invasive procedures.", "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.", "We undertook a one-year study to investigate the impact of the NSA model 7100A/B portable air filtration unit on exposure of haematology-oncology patients to airborne Aspergillus fumigatus spores under field conditions. Weekly measurements for airborne A. fumigatus were conducted in indoor and outdoor air, and surveillance for invasive aspergillosis was based on a combination of ward liaison, targeted chart review and consultation with the medical staff. The mean indoor A. fumigatus counts (8.1 cfu/m3; range, <0.8 to 42 cfu/m3) reflected the fungal load of outdoor air (9.4 cfu/m3; range, <0.8 to 50 cfu/m3), and were reduced by only about one third in rooms with portable air filtration units (5.3 cfu/m3; range, <0.8 to 41 cfu/m3). During the study period, a total of five cases (incidence density, 0.8 per 1000 patient-days) of invasive aspergillosis (one proven case, four suspected cases; case fatality rate 40%) were recorded. None of these five patients was allocated to a room with portable air filtration unit, however, the difference between incidence densities in rooms with and without portable air filtration units was non-significant (Fisher's exact test, P=0.33). Due to the noise level and thermal discomfort, patient compliance with the air filtration units was poor. We conclude that under field conditions this air filtration unit cannot be recommended for prevention of invasive aspergillosis in neutropenic haematology-oncology patients.", "Although mechanically ventilated patients experience numerous stressors, they have not been included in music therapy stress reduction and relaxation studies.\n To examine selected psychophysiologic responses of mechanically ventilated patients to music.\n A two-group experimental design with pretest, posttest, and repeated measures was used. Twenty mechanically ventilated patients were randomized to a music-listening group or a nonmusic (headphones only) group. Physiologic dependent measures--heart rate and rhythm, respiratory rate, systolic and diastolic blood pressure, oxygen saturation, and airway pressure--were collected at timed intervals. Psychologic data were collected before and after intervention using the Profile of Mood States.\n Using repeated measures analysis of variance, results for heart rate and respiratory rate over time and over time between groups were significant. Between-group differences were significant for respiratory rate. Significant differences were found via t test for the music group's Profile of Mood States scores. No adverse cardiovascular responses were noted for either group.\n Data indicated that music listening decreased heart rate, respiratory rate, and Profile of Mood States scores, indicating relaxation and mood improvement.", "To test whether use of music as a diversional intervention during high-dose chemotherapy administration would affect perception of nausea and episodes of vomiting.\n 39 patients undergoing bone marrow transplant. A total of 33 patients were included in the data analysis, with 17 in the control group and 16 in the music intervention group.\n Patients were assigned randomly to a control group (usual antiemetic protocol) or the experimental group (usual antiemetic group plus music intervention during the 48 hours of high-dose cyclophosphamide administered as part of the preparative regimen).\n Use of a music intervention, perception of nausea, and instances of vomiting.\n Significant differences were found between group scores on a visual analog scale for nausea and number of episodes of vomiting, demonstrating that the experimental group experienced less nausea and fewer instances of vomiting.\n This study found that music is an effective adjunct to a pharmacologic antiemetic regimen for lessening nausea and vomiting, and this study merits further investigation through a larger multi-institutional effort.\n Using music as a diversional adjunct intervention to antiemetic therapy is helpful in decreasing nausea and vomiting. The intervention can be initiated independently by nurses and individualized for each patient, leading to greater patient comfort and compliance with high-dose chemotherapy.", "It is known that auditory input, such as comforting music or sound, blunts the human response to surgical stress in conscious patients under regional anaesthesia. As auditory perception has been demonstrated to remain active under general anaesthesia, playing comforting sounds to patients under general anaesthesia might also modulate the response of these patients to surgical stress.\n Fifty-nine patients scheduled for laparoscopic cholecystectomy were anaesthetized with propofol general anaesthesia in combination with epidural anaesthesia. Natural sounds, chosen preoperatively by each patient as being comforting, were played to 29 patients using headphones during surgery (S group) and the remainder of the patients (n = 30) were fitted with dummy open-type headphones (N group). We compared the haemodynamic change during anaesthesia and the acceptability of anaesthetic practice between the two groups in a randomized double-blind design.\n There were no differences in haemodynamics between the S and N groups during surgery. During the emergence from anaesthesia, the mean blood pressure and heart rate gradually increased; both parameters were significantly higher in the N group than in the S group. Postoperatively, patients in the S group perceived the experience of anaesthesia as significantly more acceptable than did those in the N group.\n These findings indicate that allowing patients comforting background sounds during general anaesthesia may blunt haemodynamic changes upon emergence from general anaesthesia and increase the acceptability of the experience of anaesthesia.", "Pharmacological methods to improve postoperative pain are well documented, but an increasing interest in nonpharmacological methods has stimulated research in this field. Traditional and pharmacological interventions to relieve perioperative anxiety and pain are being challenged by an increasing demand for more holistic approaches. This study tested the hypothesis that listening to music preoperatively and postoperatively would affect patients' experience of pain, nausea, and well-being and have an impact on their vital signs. The authors conclude that a period of peaceful rest before and after surgery reduces patient anxiety.", "The purpose of this study was to examine the effects of music therapy on self-reported and physiological signs of anxiety among ambulatory patients undergoing colonoscopy. Thirty-two patients were randomly assigned to either an experimental group who listened to music during the colonoscopy or a standard procedure no music control group. Before and after the procedure, subjects completed the State Anxiety Inventory. Physiological signs of anxiety, including heart rate and blood pressure, were monitored at four time points during the procedure. Repeated measures analysis of variance indicated a significant group by time interaction on the physiological signs of anxiety. Post hoc analysis indicated that heart rate and systolic and diastolic blood pressure significantly decreased among the music intervention group during the procedure while remaining unchanged in the control group. No significant effect of the treatment was observed on the State Anxiety Inventory, although a trend indicated that the music intervention decreased state anxiety. Finally, the group who received the music intervention required less physician-administered sedation during the procedure than did the control group. These findings indicate that music therapy has the potential to reduce physiological indicators of anxiety and the need for sedation among individuals undergoing a colonoscopy.\n Copyright 2002, Elsevier Science (USA). All rights reserved.", "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.", "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 investigated the effect of humorous and musical distraction on preoperative anxiety among 46 patients scheduled for same day, elective, nondiagnostic surgery. Preoperative anxiety was measured with a horizontal visual analog scale after treatment group subjects listened to either a humorous audiotape or a tranquil music audiotape for 20 minutes and control group subjects received no intervention. Results show no significant difference between the group anxiety means. This study provides no evidence that humor or music decreases preoperative anxiety, but it also shows no evidence that perioperative nurses should avoid using humor or music as nursing interventions.", "nan", "The purpose of this study was to determine whether listening to a relaxation audiotape before and during mammography decreases subjective reports of pain and anxiety.\n Listening to a relaxation or music audiotape before and during mammography does not reduce subjective reports of anxiety or pain. Women undergoing screening mammography report minimal levels of distress.", "nan", "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 determine whether aromatherapy with lavender oil is effective in the treatment of agitated behaviour in patients with severe dementia.\n A placebo controlled trial with blinded observer rater.\n A long-stay psychogeriatric ward.\n Fifteen patients meeting ICD-10 diagnostic criteria for severe dementia and suffering from agitated behaviour defined as a minimum score of three points on the Pittsburgh Agitation Scale (PAS).\n A 2% lavender oil aromatherapy stream was administered on the ward for a two hour period alternated with placebo (water) every other day for a total of ten treatment sessions.\n For each subject 10 total PAS scores were obtained. Five during treatment and five during placebo periods.\n Nine patients (60%) showed an improvement, five (33%) showed no change and one patient (7%) showed a worsening of agitated behaviour during aromatherapy compared with placebo. A comparison of the group median PAS scores during aromatherapy showed a significant improvement in agitated behaviour during aromatherapy compared with placebo (median PAS scores 3 c.f. 4; Wilcoxon Signed-Ranks test p = 0.016 (one-tailed)).\n Lavender oil administered in an aroma stream shows modest efficacy in the treatment of agitated behaviour in patients with severe dementia.\n Copyright 2002 John Wiley & Sons, Ltd.", "Ninety ASA I-II patients scheduled for a pre-planned surgical operation were randomly assigned to three groups: the first of these received no premedication, the second received 1-2 ml Thalamonal i.m., and the third were offered music from a walkman via earphones. Excluded from the study were patients under 15 and over 65 years of age, patients suffering from malignant diseases, those expecting operations of uncertain outcome, and patients whose mother tongue was not German. All 90 patients were cared for by the same investigator. She obtained informed consent on the eve of the scheduled operation and chose the music that was to be offered preceding the operation according to the patient's wishes. Each patient's history was evaluated, including the grade of anxiety and his or her attitude towards music. Of course, a physical examination was also conducted. Ninety minutes prior to the operation, psychometric tests (STAI-G-X2, STAI-G-X1, ESA-S, and BF-S) were performed. Thereafter, either music was offered or else 1-2 ml Thalamonal was injected, according to the random assignment: group 1 received neither. Fifteen minutes before entering the operating room, the tests expressing anxiety with regard to the situation were repeated as was the physical examination, and the investigator once again assessed the level of anxiety of the patients. On the evening of the day of surgery, all patients were asked to give an evaluation of the preoperative period. Trait-anxiety, as measured by the STAI-G-X2-Test, was comparable in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "The role of music therapy as a supportive treatment is not well defined. The music therapy cannot be estimated as the isolated method it is often only the part of the complex therapy. The aim of this study was to evaluate the influence of music therapy on anxiety level in hospitalized asthmatic patients. The patient group was consisted of 36 patients with bronchial asthma (23 women and 13 men). In all patients we evaluated the level of anxiety (attribute and state) according to Spielberger and intensity of dyspnoe according to Borg scale at the first day of examination and after 10 days of rehabilitation program. Moreover we performed spirometry. The respiratory rehabilitation program included: exercise of breath control, correction of respiratory pattern, training of diaphragm and additional respiratory muscles. The duration of music therapy lasted 15 min. After 10 days rehabilitation with or without music therapy we found the reduction of anxiety (state) (p<0.0001). However we did not observe the difference between two studied groups with or without music therapy in diminishing of anxiety (p = 0.55). In conclusion, we believe that the music therapy can play important role in treatment of somatic disease but our study did not confirm its additive positive meaning in patients with bronchial asthma.", "Previous studies have indicated that music decreases intraoperative sedative requirements in patients undergoing surgical procedures under regional anesthesia. In this study we sought to determine whether this decrease in sedative requirements results from music or from eliminating operating room (OR) noise. A secondary aim of the study was to examine the relationship of response to intraoperative music and participants' culture (i.e., American versus Lebanese). Eighty adults (36 American and 54 Lebanese) undergoing urological procedures with spinal anesthesia and patient-controlled IV propofol sedation were randomly assigned to intraoperative music, white noise, or OR noise. We found that, controlling for ambient OR noise, intraoperative music decreases propofol requirements (0.004 +/- 0.002 mg . kg(-1) . min(-1) versus 0.014 +/- 0.004 mg . kg(-1) . min(-1) versus 0.012 +/- 0.002 mg . kg(-1) . min(-1); P = 0.026). We also found that, regardless of group assignment, Lebanese patients used less propofol as compared with American patients (0.005 +/- 0.001 mg . kg(-1) . min(-1) versus 0.017 +/- 0.003 mg . kg(-1) . min(-1); P = 0.001) and that, in both sites, patients in the music group required less propofol (P < 0.05). We conclude that when controlling for ambient OR noise, intraoperative music decreases propofol requirements of both Lebanese and American patients who undergo urological surgery under spinal anesthesia.", "nan", "To elucidate the multifactorial nature of perioperative changes in body temperature, the influence of several clinical variables, including anesthetic technique, ambient operating room temperature, and age, were evaluated. Perioperative oral sublingual temperatures were measured in 97 patients undergoing lower extremity vascular surgery randomized to receive either general (GA) or epidural (EA) anesthesia. Surgery and anesthesia were performed in operating rooms (OR) with a relatively warm mean ambient temperature (24.5 +/- 0.4 degrees C) (GA, n = 30; EA, n = 33) or relatively cold mean ambient temperature (21.3 +/- 0.3 degrees C) (GA, n = 21; EA, n = 13). Patients were 35-94 yr old, with a mean age of 64.5 +/- 1.1 yr. A regression analysis was performed to determine the variables that correlated with intraoperative decrease in temperature and postoperative rewarming rate. The major correlates of greater intraoperative decrease in temperature were 1) GA (P = 0.003); 2) cold ambient OR temperature (P = 0.07); and 3) advancing patient age (P = 0.03). There was significant interaction between ambient OR temperature and type of anesthesia (P = 0.03): there was a greater intraoperative decrease in temperature with GA compared to EA in a cold OR but a similar decrease with GA and EA in a warm OR. The data also suggest an interaction between type of anesthesia and patient age (P = 0.06), showing a greater decrease in temperature with GA compared to EA in the younger patients, but a similar decrease between GA and EA in older patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "The sedating effect and influence of walkman music on 120 patients, that were randomly divided into a music and non-music group, who had received epidural anesthesia were investigated. It was found that significantly fewer patients in the music group felt anxious during surgery (P = 0.049). Meanwhile, heart rate and mean arterial pressure of the non-music group remained at a higher level, resulting in higher heart loading. Furthermore, patients listening to music had a significantly smaller need of sedatives (P = 0.001). With the purpose of reducing the consumption of sedatives, and offering a better anesthetic environment, we recommend the use of music during regional anesthesia.", "Patient anxiety related to flexible sigmoidoscopy can negatively affect acceptability and compliance with screening protocol, complicate and prolong procedure time, and potentially result in prematurely aborted procedures. Music has been recognized through research as a safe, inexpensive, and effective nonpharmaceutical anxiolitic agent.\n An experimental study was performed on 50 adults scheduled for outpatient sigmoidoscopy. The control group received standard sigmoidoscopy protocol. Subjects in the experimental group received the standard protocol with the addition of listening to music throughout the procedure. State-Trait Anxiety Inventory (STAI) measurements were performed on all subjects before and postsigmoidoscopy. Physiologic recordings of heart rate and mean arterial pressure were recorded before and during the procedure.\n Patients who listened to self-selected music tapes during the procedure had significantly decreased STAI scores (P < 0.002), heart rates (P < 0.03), and mean arterial pressures (P < 0.001) in comparison to the control subjects.\n The results of the study indicate that music is an effective anxiolitic adjunct to flexible sigmoidoscopy.", "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.", "An experimental pilot study was conducted to investigate the effects of preoperative massage and music therapy on patients' preoperative, intraoperative, and postoperative experiences. Participants were assigned randomly to one of four groups--a group that received massage with music therapy, a group that received massage only, a group that received music therapy only, or a control group. Hemodynamics, serum cortisol and prolactin levels, and anxiety were measured preoperatively and postoperatively. Postoperative anxiety levels were significantly lower and postoperative prolactin levels were significantly higher for all groups.", "The purpose of this study was to determine whether cognitive appraisals of stress level and hypertensive responses to ambulatory ophthalmic surgery can be ameliorated by patient-selected music.\n We studied 40 elderly individuals requiring ophthalmic surgery, 20 in an experimental group (mean age, 74 years) and 20 in a control group (mean age, 77 years). All patients had an established resting blood pressure <140/90 mm Hg. In the experimental group self-selected music was provided by headphones throughout the preoperative, surgical, and postoperative periods. In the control group patients had neither headphones nor music. All patients received similar (weight-determined) doses of alfentanil and midazolam during surgery. Heart rate, blood pressure, and patient-reported stress and coping levels were the dependent variables.\n In both groups, blood pressure values were normal (approximately 129/82 mm Hg) during screening examinations 1 week before surgery. On the day of surgery both groups displayed increased preoperative blood pressures (approximately 159/92 mm Hg) associated with increases in heart rate (by approximately 17 beats/min). Intraoperative blood pressures in the experimental group returned quickly to screening baseline values, whereas the control group experienced persistent elevations in intraoperative blood pressure similar to preoperative levels. Over the course of the surgical experience, patients with music reported significant reductions in perceived stress and increases in coping abilities (p < .001), whereas those without music did not.\n The perceived stress of ambulatory surgery in geriatric patients is associated with a clinical hypertensive response that is ameliorated by self-selected perioperative music, which also decreases perceived stress and increases patients' sense of personal control and well-being.", "Patients scheduled for bronchoscopic procedures are often anxious and frightened. Reduction in the state of anxiety during an invasive procedure may prevent some possible complications. Music has been proposed as a safe nonpharmacological antianxiety intervention.\n We followed up physiological indicators of anxiety (blood pressure, heart rate) during bronchoscopic examination to determine the effect of music on the level of anxiety.\n Two hundred adult patients were included in the study. Blood pressure, heart rate, procedures performed during bronchoscopy and duration of examination were monitored. Patients' overall feelings during the procedure were rated from 0 (without unpleasant feelings) to 10 (unbearable). All patients used the Visual Analogue Scale (VAS).\n Two hundred adult patients referred for bronchoscopy were included in the study: 93 patients received music during the procedure and 107 served as control. There were no significant differences between the two groups in terms of age, sex, indications for bronchoscopy, procedures performed during bronchoscopy, duration of the examination and patients' subjective perception of the procedure. The mean hart rate, systolic and diastolic blood pressures were significantly lower in the music group compared to the control group.\n Our findings suggest that the application of music reduces anxiety during bronchoscopic examination as physiological indicators of anxiety, the mean heart rate, systolic and diastolic blood pressures, were significantly lower in the music group.\n Copyright 2006 S. Karger AG, Basel.", "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.", "nan", "nan", "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.", "We assessed the effect of music on the level of sedation and the electroencephalograph bispectral index (BIS) during the preoperative period. Fifty-four ASA physical status I-II patients, scheduled for elective septo-rhinoplastic surgery, were included in the study. Subjects were assigned to receive either music (music group; n = 28) or no music (control group; n = 26) during the preoperative period. Sedative premedication was provided with midazolam 0.08 mg/kg IM. Observer's Assessment of Alertness/Sedation Scales (OAAS) scores and BIS values were recorded at specific time intervals. In the control group, there were more patients with an OAAS score of 1 than in the music group at 30 min after midazolam injection. In addition, there were more patients with an OAAS score of 2 in the control group than in the music group at 30-50 min. However, there were significantly more patients with an OAAS score of 3 in the music group than in the control group at 20-50 min. BIS values of the music group were also smaller than the control group at 30 and 40 min. BIS values were significantly decreased from baseline values at 10-50 min in the music group, whereas BIS values decreased at 30-50 min in the control group. In conclusion, listening to music during midazolam premedication is associated with an increase in sedation level in the preoperative period as reflected by a lower BIS value.", "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.", "A series of 24 patients with severe neutropenia, most of whom had acute myeloblastic leukemia, were treated in an isolation unit with oral nonabsorbable antibiotics and were compared to 21 similar patients receiving oral antibiotics alone. The frequency of bacterial infections was lower in the patients receiving both isolation and oral antibiotics compared to the patients who received only oral antibiotics. The responses to chemotherapy in terms of remission rates were identical for the two groups.", "In this experimental study we examined the effects of listening to relaxation-type music on self-reported anxiety and on selected physiologic indices of relaxation in patients with suspected myocardial infarction. Seventy-five patients were randomly assigned to one of two experimental groups, one listening to music and the other to \"white noise,\" or to a control group. The State Anxiety Inventory was administered before and after each testing session, and blood pressure, heart rate, and digital skin temperature were measured at baseline and at 10-minute intervals for the 30-minute session. There was no significant difference among the three groups for state anxiety scores or physiologic parameters. Because no differences were found, analyses were conducted of the groups combined. Significant improvement in all of the physiologic parameters was found to have occurred. This finding reinforces the need for nurses to plan care that allows for uninterrupted rest for patients in the coronary care unit.", "Many patients in the Surgical Holding Area become stressed and anxious. In a hospital setting music reduces patients' anxiety. This study determined that music can reduce the anxiety and stress of patients in the Surgical Holding Area. In this study, one group of subjects listed to music while a second group did not. Subjects who listened to music while in the Surgical Holding Area had significantly less stress and anxiety than did those who did not listen to music. Both groups spent similar lengths of time in the Surgical Holding Area. The results strongly suggest that if music were available to all patients in the Surgical Holding Area, most would select this option, and they would experience less anxiety.", "Fifty-eight elderly hospital patients walked along a 10-m length of carpeted corridor and a 10-m length of vinyl-tiled corridor. Gait speed and step length were significantly greater on the carpeted than on the vinyl surface.", "To study the effect of music on state anxiety levels in patients undergoing flexible fiberoptic bronchoscopy (FFB).\n Randomized clinical trial using pretests, posttests, and two groups.\n Pulmonary special-procedures unit of a tertiary-care referral center.\n Sixty adult patients: 30 patients received music during bronchoscopy and 30 control subjects received no music.\n The study population had baseline state anxiety levels similar to those previously reported in surgical patients (42.6 +/- 13 vs 42.7 +/- 14; p value, not significant [NS]) and higher than those reported in normal working adults (42.6 +/- 13 vs 34.4 +/- 10; p < 0.001). Experimental and control groups were similar in patient and procedure-related characteristics and baseline pre-FFB state and trait anxiety scores. Although trait anxiety scores decreased significantly after the procedure (pooled post-FFB scores of 32.6 +/- 10 vs pre-FFB scores of 35.5 +/- 11; p < 0.001), no reductions were noted in state anxiety (pooled post-FFB scores of 42.8 +/- 13 vs pre-FFB scores of 42.6 +/- 13; p value, NS). More importantly, playing music through headphones during FFB did not result in a statistically or clinically significant reduction in either state or trait anxiety when compared to control subjects.\n Relaxation music administered through headphones to patients during flexible bronchoscopy does not decrease procedure-related state anxiety.", "Patients scheduled for gastrointestinal procedures such as colonoscopy or esophagogastroduodenoscopy are often anxious and frightened. High levels of anxiety may result in more difficult and painful procedures. Past research has reported education, coping skills, relaxation techniques, and combinations of these including music, have decreased anxiety in patients across many settings. Self-selected music therapy for preprocedural anxiety has not been studied. A randomized controlled trial of 198 patients was undertaken to determine whether 15 minutes of self-selected music reduced preprocedure anxiety. The State Trait Anxiety Inventory was used to measure patients' anxiety. One-hundred ninety-three men and 5 women comprised the sample with an average age of 61 (SD 10.5). Patients who listened to music (n = 100) reduced their anxiety score from 36.7 (SD 9.1) to 32.3 (SD 10.4), while those who did not listen to music (n = 98) reduced their anxiety score from 36.1 (SD 8.3) to 34.6 (SD 11.5). These differences were statistically significant (F = 7.5, p =.007) after controlling for trait anxiety. There were no significant vital sign changes premusic and postmusic. Music is a noninvasive nursing intervention that can significantly reduce patients' anxiety prior to gastrointestinal procedures. Further research should address using music to reduce anxiety in other procedure areas and testing effectiveness of self-selected versus investigator-selected music in reducing anxiety.", "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.", "Despite current recommendations calling for regular screening flexible sigmoidoscopies over the age of 50, only a small percentage of the population have regular examinations. Improving patient tolerance of flexible sigmoidoscopies could therefore increase patient compliance with these recommended guidelines. The aim of this study was to determine whether audio and visual stimulation reduces discomfort during flexible sigmoidoscopy and whether the effects of the stimulation are secondary to distraction.\n A total of 37 patients undergoing routine screening flexible sigmoidoscopy were randomized to receive no intervention, audio stimulation alone, or audio and visual stimulation. Patient discomfort ratings and affect states were measured prior to and immediately following flexible sigmoidoscopy using a visual analogue scale and the Stress Symptom Ratings (SSR) ratings.\n Patients receiving audio and visual intervention had lower abdominal discomfort ratings (7.1 +/- 1.4) than patients receiving audio stimulation (9.5 +/- 1.3) or no intervention (10.8 +/- 1.6) (p < 0.05). Patients receiving audio and visual intervention also had higher arousal (7.3 +/- 0.4) and attention (9.2 +/- 0.2) ratings than patients receiving no intervention (6.1 +/- 0.4 and 6.2 +/- 0.7, respectively) (p < 0.05). Anxiety and anger ratings, on the other hand, were significantly lower in patients receiving audio and visual intervention (2.5 +/- 0.4, 1.4 +/- 0.3, respectively) than patients receiving no intervention (4.4 +/- 0.6, 3.6 +/- 0.7).\n Audio and visual stimulation reduces abdominal discomfort associated with flexible sigmoidoscopy. This effect appears to be due to distraction.", "Unrelieved anxiety can produce an increase in sympathetic nervous system activity leading to an increase in cardiac workload. Nursing interventions using music therapy or sensory information among patients with coronary artery disease has resulted in anxiety reduction, though results in Chinese subjects has not previously been published.\n To determine the effects of using nursing interventions of music therapy or sensory information, on reducing anxiety and uncertainty, and improving negative mood among Chinese subjects immediately prior to cardiac catheterization.\n An experimental three-group repeated measures design for this pilot study was used. Forty-five hospitalized adults (15/group) undergoing cardiac catheterization were randomly assigned to either (1) a music therapy intervention, (2) a sensory information intervention or (3) treatment as usual (control). Anxiety, uncertainty and mood state were measured using self-reported questionnaires and physiological measures were made at baseline, post-intervention to determine their effect and post-cardiac catheterization to determine whether these interventions had any long-lasting effect.\n The control group was found to be significantly older (P=0.001) than the two experimental groups. Older age was associated with lower anxiety scores (r=-0.31, P=0.04 at baseline; r=-0.30, P=0.04 post-intervention; r=-0.22, P=0.15 post-cardiac catheterization). After controlling for age, the use of music therapy or sensory information did not significantly reduce anxiety, improve mood state, reduce uncertainty, decrease heart or respiratory rate among subjects undergoing cardiac catheterization.\n The non-significant result may have been affected by the small sample, and the social and cultural expectations regarding the public display of emotions among Chinese populations.", "Ambulatory surgery can create significant anxiety. This prospective study measured whether music can influence anxiety and perioperative sedative requirements in outpatients undergoing surgery with spinal anesthesia. We also evaluated the correlation between two anxiety measures, the State-Trait Anxiety Inventory test (STAI) and the 0- to 10-cm visual analog scale (VAS 0-10), with 0 meaning complete relaxation and 10 the worst feeling of anxiety possible. Fifty unpremedicated patients were randomly assigned to listen to music of their choice via headset during the perioperative period (Group I) or to have no music (Group II). All participants used patient-controlled IV midazolam sedation and underwent repeated evaluations of their anxiety level with the STAI and the VAS 0-10. Midazolam requirements during surgery (Group I, 0.6 +/- 0.7 versus Group II, 1.3 +/- 1.1 mg; P < 0.05) and for the whole perioperative period (Group I, 1.2 +/- 1.3 versus Group II, 2.5 +/- 2.0 mg; P < 0.05) were smaller in patients listening to music. Anxiety levels, measured with STAI or VAS 0-10, were similar in both groups. The Spearman's coefficient values between STAI and VAS 0-10 ranged from 0.532 to 0.687. We conclude that patients listening to music require less midazolam to achieve a similar degree of relaxation as controls and that measures of anxiety obtained from the STAI and the VAS 0-10 are positively, but only moderately, correlated.\n It is possible to decrease sedative requirements during surgery under spinal anesthesia by allowing patients to listen to music to reduce their anxiety.", "Acute myocardial infarction places additional demands on an already compromised myocardium. Relaxing music can induce a relaxation response, thereby reversing the deleterious effects of the stress response.\n To compare the effects of relaxing music; quiet, uninterrupted rest; and \"treatment as usual\" on anxiety levels and physiological indicators of cardiac autonomic function.\n A 3-group repeated measures experimental design was used. Forty-five patients, 15 per group, with acute myocardial infarction were assigned randomly to 20 minutes of (1) music in a quiet, restful environment (experimental group); (2) quiet, restful environment without music (attention); or (3) treatment as usual (control). Anxiety levels and physiological indicators were measured.\n Immediately after the intervention, reductions in heart rate, respiratory rate, and myocardial oxygen demand were significantly greater in the experimental group than in the control group. The reductions in heart rate and respiratory rate remained significantly greater 1 hour later. Changes in heart rate, respiratory rate, and myocardial oxygen demand in the attention group did not differ significantly from changes in the other 2 groups. The 3 groups did not differ with respect to systolic blood pressure. Increases in high-frequency heart rate variability were significantly greater in the experimental and attention groups than in the control group immediately after the intervention. State anxiety was reduced in the experimental group only; the reduction was significant immediately and 1 hour after the intervention.\n Patients recovering from acute myocardial infarction may benefit from music therapy in a quiet, restful environment.", "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.", "Pain related to the gurney is a frequent complaint of older emergency department (ED) patients. The authors hypothesized that these patients may have less pain and higher satisfaction if allowed to sit in a reclining hospital chair.\n A single-blind, randomized controlled trial was performed. Patients 65 years old or older who were able to sit upright, transfer, and engage in normal conversation were eligible. Severely ill or cognitively impaired patients were excluded. Patients were randomized to either remain on the gurney or transfer to the chair after initial evaluation. Patients reported pain at arrival (t0), at one hour (t1), and at two hours (t2) using a 0-10 pain scale, and satisfaction at study completion on a 0-10 scale. The primary outcome was a decrease in pain between t0 and t1 or no pain at both t0 and t1. This outcome was analyzed using a 95% confidence interval for the difference between proportions; exclusion of zero was considered significant.\n Sixty-six patients in each group were enrolled. There was no difference in demographics between groups, but the chair patients were more likely to have pain at t0 than the gurney patients. More chair patients than gurney patients had a successful primary outcome (97% vs. 76%, 21% difference, 95% CI=10% to 32%). The mean satisfaction score was higher in the chair group than in the gurney group (8.1 vs. 6.0, 2.1 difference, 95% CI=1.4% to 2.8%).\n The simple modification of allowing older ED patients to sit in reclining chairs resulted in less pain and higher satisfaction.", "The aim of this study was to investigate the effects of music on the anxiety of patients on mechanical ventilation, as assessed by objective parameters and a subjective validated anxiety scale.\n Mechanical ventilation, although sometimes lifesaving, is often associated with levels of anxiety requiring sedatives, which has inevitable implications on costs and complications.\n A randomized controlled trial design.\n A total of 64 subjects was randomly assigned to undergo either 30 minutes of music intervention or a rest period. The subjects were asked to answer the Chinese State Trait Anxiety Inventory scale before and after the study period and physiological indices and resting behaviours were recorded before and after the study period in both groups. The subjects' satisfaction with music was also obtained after music intervention.\n The findings indicate that patients on mechanical ventilation that listened to a single 30-minute session of music appeared to show greater relaxation as manifested by a decrease in physiological indices and an increase in comfortable resting behaviours.\n Music can provide an effective method of reducing potentially harmful physiological responses arising from anxiety in mechanically ventilated patients.\n As indicated by the results of this study, music therapy can act as a simple and safe nursing intervention to allay anxiety and promote patient comfort. Interest and comments on music therapy provided as a relaxation technique should be elicited from both nurses and patients.", "To determine whether music moderates the level of anxiety that patients experience during radiation therapy.\n Experimental, longitudinal, random assignment to music or no music therapy.\n Urban radiation oncology center in a Department of Veterans Affairs hospital in the southeastern United States.\n Forty-two men (19 in the experimental group, 23 in the control group) aged 39-80 years (74% white, 12% African American, 12% Hispanic, and 2% other) receiving definitive external beam radiation therapy for pelvic or abdominal malignancies.\n Patients in the experimental group listened to music of their choice provided via audiotapes and headphones before and during their simulation and daily treatments for the duration of the planned course of therapy. The control group received standard care. The State-Trait Anxiety Inventory was administered initially to participants in both groups at the time of evaluation (time 1), post-simulation (time 2), at the end of the first week (time 3), at the end of the third week (time 4), and at the end of the fifth week or end of radiation therapy (time 5).\n State anxiety.\n No significant difference existed between the two groups to suggest that music moderated the level of anxiety during radiotherapy. However, post-hoc analyses identified changes and trends in state anxiety scores, suggesting a possible benefit of music therapy during radiotherapy.\n Despite a lack of group differences, early intervention with music therapy for patients with high levels of anxiety may be beneficial.\n Nurses and other clinicians may administer state anxiety scales at the initial visit or prior to pretreatment radiation planning (simulation). Individuals who have high state anxiety scores may receive nursing interventions tailored to reduce anxiety during simulation and the early part of radiotherapy.", "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.", "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.", "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.", "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.", "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.", "Music has long been known to reduce anxiety, minimize the need for sedatives, and make patients feel more at ease. The purpose of the study was to evaluate the effect of music in elderly outpatients undergoing elective cataract surgery with retrobulbar block and monitored anaesthetic care using fentanyl or alfentanil and midazolam.\n One hundred and twenty one patients were prospectively and randomly assigned to hear: relaxing suggestions, white noise, operating room noise or relaxing music via audio-cassette headphones. Vital signs were documented before and after retrobulbar block and every 15 min thereafter. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) before and after surgery. Visual analogue scales (VAS) were used to assess anxiety and patient satisfaction postoperatively with a standardized questionnaire. Between group comparisons were made using Chi-Square, or ANOVA, where appropriate.\n There were no differences between groups in STAI or anxiety VAS scores at any time. Differences were noted in systolic blood pressure, but not in other vital signs. Patients' ratings of the whole operative experience, satisfaction with the tape played, general level of relaxation and preference for the chosen tape for subsequent surgery were different (music > relaxing suggestions > white noise and OR noise, P < 0.05).\n Elderly patients undergoing cataract surgery under retrobulbar block were more satisfied with their experience if they heard relaxing music, rather than relaxing suggestions or white noise or OR noise. The type of auditory stimuli to which the patients were exposed did not influence the level of anxiety.", "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.", "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.", "Open-heart surgery patients report anxiety and pain with chair rest despite opioid analgesic use. The effectiveness of non-pharmacological complementary methods (sedative music and scheduled rest) in reducing anxiety and pain during chair rest was tested using a three-group pretest-posttest experimental design with 61 adult postoperative open-heart surgery patients. Patients were randomly assigned to receive 30 min of sedative music (N=19), scheduled rest (N=21), or treatment as usual (N=21) during chair rest. Anxiety, pain sensation, and pain distress were measured with visual analogue scales at chair rest initiation and 30 min later. Repeated measures MANOVA indicated significant group differences in anxiety, pain sensation, and pain distress from pretest to posttest, P<0.001. Univariate repeated measures ANOVA (P< or =0.001) and post hoc dependent t-tests indicated that in the sedative music and scheduled rest groups, anxiety, pain sensation, and pain distress all decreased significantly, P<0.001-0.015; while in the treatment as usual group, no significant differences occurred. Further, independent t-tests indicated significantly less posttest anxiety, pain sensation, and pain distress in the sedative music group than in the scheduled rest or treatment as usual groups (P<0.001-0.006). Thus, in this randomized control trial, sedative music was more effective than scheduled rest and treatment as usual in decreasing anxiety and pain in open-heart surgery patients during first time chair rest. Patients should be encouraged to use sedative music as an adjuvant to medication during chair rest.", "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.", "The sedative effects of music were evaluated using the bispectral index (BIS) during target-controlled infusion (TCI) propofol. A total of 110 women undergoing hysterectomy were randomly allocated to receive either music or no music. Propofol was administered using target-controlled infusion and the concentration adjusted gradually to achieve an observer's assessment of alertness/sedation (OAA/S) score of 3 intra-operatively. The haemodynamic and bispectral index values during the sedation phase were recorded. Interleukin-6 was evaluated before, immediately after and 1 h following intervention. The music group had a significant reduction in mean (SD) induction time of sedation: 12 (12) min vs. 18 (12) min, p < 0.01; propofol target concentration: 1.6 (0.3) microg.ml(-1) vs. 2.4 (0.4) microg.ml(-1), p < 0.0001; intra-operative amount of propofol: 171 (98) mg vs. 251 (92) mg, p < 0.0001; and significantly higher levels of satisfaction with their peri-operative care: 9.6 (0.6) compared to the control group: 8.1 (1.0), p < 0.0001. No other differences were found. The results show the influence of music on the induction time of sedation, concentration and level of propofol during surgery, and suggest sedative benefits of music.", "The objective of the study was to compare development in symptoms, behaviours, treatment and patient satisfaction of a traditional interior and an interior furnished like an ordinary home in a seclusion area. A naturalistic sample of 56 consecutive patients admitted to an acute ward was allocated to two different seclusion areas, one with a traditional interior and one decorated as an ordinary home. Symptoms of psychopathology, therapeutic steps taken, violent episodes, length of patient stay and patient satisfaction were recorded. There were no differences in changes in scores on The Positive and Negative Syndrome Scale for schizophrenia, The Brøset Violence Checklist or the Global Assessment of Function split version scale between the two patient groups. Therapeutic steps taken, number of violent episodes and length of patient stay was also similar. Female patients preferred an ordinary home interior. It was concluded that interior and furnishing like an ordinary home in the seclusion areas created an environment with comparable treatment outcomes to the traditional dismal interior, and had positive effects on many patients' well-being, at least among the women. The traditional beliefs that a sparsely decorated interior is a method to reduce symptoms of psychopathology and dangerous behaviours were not supported by our data.", "Colonoscopies are usually performed using pharmacological sedation. This process entails certain risks. In the search for alternative methods, some studies have analysed the effect music can have on patients during the procedure when used as a complement to sedation. We present a prospective, randomized study in which we assess the anxiolytic action music has when it is administered during a single colonoscopy.\n We included 118 patients who were scheduled for ambulatory colonoscopies. They were randomly assigned to the control group (n = 55) and the experimental group (n = 63). We determined their levels of anxiety using the State-Trait Anxiety Inventory Test (STAI) form, which they filled in before and after the examination. Patients listened to music through personal headphones.\n The score on the STAI form before the examination was 25.25 +/- 10.49 and 28.16 +/- 11.43 in the control and experimental groups, respectively (P > 0.05). The decrease of the score on the STAI scale after the colonoscopy in the control and experimental groups was 6.27 (95% confidence interval, 3.26-9.28) and 11.35 (95% confidence interval, 8.64-14.05), respectively (P < 0.01).\n Listening to music during ambulatory colonoscopies decreases the level of anxiety that is inherent to the process without other anxiolytic methods.", "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.", "This paper reports a study to test the hypothesis that day surgery patients who listen to music during their preoperative wait will have statistically significantly lower levels of anxiety than patients who receive routine care.\n Although previous day surgery research suggests that music effectively reduces preoperative anxiety, methodological issues limit the generalizability of results.\n In early 2004, a randomized controlled trial design was conducted to assess anxiety before and after listening to patient preferred music. Participants were allocated to an intervention (n=60), placebo (n=60) or control group (n=60). Pre- and post-test measures of anxiety were carried out using the State-Trait Anxiety Inventory.\n Music statistically significantly reduced the state anxiety level of the music (intervention) group. No relationships were found between socio-demographic or clinical variables such as gender or type of surgery.\n The findings support the use of music as an independent nursing intervention for preoperative anxiety in patients having day surgery.", "This randomized controlled trial was designed to evaluate, first, whether intra- or postoperative music therapy could influence stress and immune response during and after general anaesthesia and second, if there was a different response between patients exposed to music intra- or postoperatively.\n Seventy-five patients undergoing open hernia repair as day care surgery were randomly allocated to three groups: intraoperative music, postoperative music and silence (control group). Anaesthesia and postoperative analgesia were standardized and the same surgeon performed all the operations. Stress response was assessed during and after surgery by determining the plasma cortisol and blood glucose levels. Immune function was evaluated by studying immunoglobulin A (IgA) levels. Patients' postoperative pain, anxiety, blood pressure (BP), heart rate (HR) and oxygen saturation were also studied as stress markers.\n There was a significantly greater decrease in the level of cortisol in the postoperative music group vs. the control group (206 and 72 mmol L(-1) decreases, respectively) after 2 h in the post anaesthesia care unit. The postoperative music group had less anxiety and pain and required less morphine after 1 h compared with the control group. In the postoperative music group the total requirement of morphine was significantly lower than in the control group. The intraoperative music group reported less pain after 1 h in the post anaesthesia care unit. There was no difference in IgA, blood glucose, BP, HR and oxygen saturation between the groups.\n This study suggests that intraoperative music may decrease postoperative pain, and that postoperative music therapy may reduce anxiety, pain and morphine consumption.", "We previously demonstrated that audio distraction using relaxation music could lead to a decrease in the dose of sedative medication required and improve patient satisfaction during colonoscopy. This prospective randomized controlled trial was designed to test the hypotheses that visual distraction may also decrease the requirement for sedatives and that audio and visual distraction may have additive beneficial effects when used in combination.\n 165 consecutive patients who underwent elective colonoscopy were randomly allocated into three groups to receive different modes of sedation: group 1 received visual distraction and patient-controlled sedation (PCS); group 2 received audiovisual distraction and PCS; group 3 received PCS alone. A mixture of propofol and alfentanil, delivered by a Graseby 3300 PCA pump, was used for PCS in these groups. Each bolus of PCS delivered 4.8 mg propofol and 12 micro g alfentanil. Measured outcomes included the dose of PCS used, complications, recovery time, pain score, satisfaction score, and willingness to use the same mode of sedation if the procedure were to be repeated.\n Eight patients were excluded after randomization. The mean+/-SD dose of propofol used in group 2 (0.81 mg/kg +/- 0.49) was significantly less than the dose used in group 1 (1.17 mg/kg +/- 0.81) and that used in group 3 (1.18 mg/kg +/- 0.60) ( P < 0.01, one-way analysis of variance). The mean +/- SD pain score was also lower in group 2 (5.1 +/- 2.5), compared with the pain scores in group 1 (6.2 +/- 2.2) and group 3 (7.0 +/- 2.4) ( P < 0.01, one-way analysis of variance). The mean +/- SD satisfaction score was higher in groups 1 (8.2 +/- 2.4)) and 2 (8.4 +/- 2.4), compared with the score in group 3 (6.1 +/- 2.9) ( P < 0.01, one-way analysis of variance). A majority of patients in groups 1 (73 %) and 2 (85 %) said that they would be willing to use the same mode of sedation again, compared with only 53 % in group 3 ( P < 0.01, chi-squared test).\n Visual distraction alone did not decrease the dose of sedative medication required for colonoscopy. When audio distraction was added, both the dose of sedative medication required and the pain score decreased significantly. Both visual and audiovisual distraction might improve patients' acceptance of colonoscopy.", "Pre-operative anxiety is common and often significant. Ambulatory surgery challenges our pre-operative goal of an anxiety-free patient by requiring people to be 'street ready' within a brief period of time after surgery. Recently, it has been demonstrated that music can be used successfully to relieve patient anxiety before operations, and that audio embedded with tones that create binaural beats within the brain of the listener decreases subjective levels of anxiety in patients with chronic anxiety states. We measured anxiety with the State-Trait Anxiety Inventory questionnaire and compared binaural beat audio (Binaural Group) with an identical soundtrack but without these added tones (Audio Group) and with a third group who received no specific intervention (No Intervention Group). Mean [95% confidence intervals] decreases in anxiety scores were 26.3%[19-33%] in the Binaural Group (p = 0.001 vs. Audio Group, p < 0.0001 vs. No Intervention Group), 11.1%[6-16%] in the Audio Group (p = 0.15 vs. No Intervention Group) and 3.8%[0-7%] in the No Intervention Group. Binaural beat audio has the potential to decrease acute pre-operative anxiety significantly.", "nan" ]

[ "3042005", "5061840", "9810966", "11505880", "4579368", "2672426", "10584839", "3574383" ]

[ "[Intravenous hydrocortisone in large doses in the treatment of delayed ischemic neurological deficits following subarachnoid hemorrhage--results of a multi-center controlled double-blind clinical study].", "Cerebrospinal fluid pressure changes with chemotherapy for intracerebral hemorrhage.", "Dexamethasone is not necessarily unsafe in primary supratentorial intracerebral haemorrhage.", "Effectiveness of high dose dexamethasone in the treatment of acute stroke.", "Dexamethasone as treatment in cerebrovascular disease. 1. A controlled study in intracerebral hemorrhage.", "Effect of fludrocortisone acetate in patients with subarachnoid hemorrhage.", "Improved efficiency of hypervolemic therapy with inhibition of natriuresis by fludrocortisone in patients with aneurysmal subarachnoid hemorrhage.", "Effects of dexamethasone in primary supratentorial intracerebral hemorrhage." ]

[ "Glucocorticoid in high dose has known to reduce vascular sensitivity to various vasoconstrictive stimuli. It inhibits phospholipase to reduce production of prostaglandins. It stabilizes the cell membrane and prevents cerebral edema. All these pharmacological effects indicate possible usefulness of this drug for the treatment of cerebral ischemia due to vasospasm. Based on these theoretical backgrounds a multi-center controlled double blind clinical study was carried out. The patient who showed manifestations of delayed cerebral ischemia due to vasospasm were selected for this study. As soon as the clinical manifestation appeared, the patient was given either 3 grams of hydrocortisone intravenously in a 60 ml solution or the placebo. The administration was repeated 6 times with interval of 12 hours. The patients were allowed to be treated according to the independent protocol of each institute except for the maximum daily use of glucocorticoid. The effect of the therapy was evaluated at 4th, 7th day and 1 month after the initiation. The study involved 52 institutes and a total of 140 patients, seventy-one patients who received hydrocortisone (group A) and 69 patients who received placebo (group P) was analysed. There were no significant differences in background data between both groups. In patients with grade I, II or III on admission, the favorable effects of hydrocortisone were demonstrated on changes in neurological findings. In group A, there were significantly more cases of improvement at 4th day for orientation about place and person. At 1 month or on discharge group A showed significant improvement almost in every aspect of neurological findings including mental, speech and motor functions.(ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "nan", "A prospective double-blind placebo-controlled, randomised clinical trial was carried out to determine the effectiveness of short-course of high dose dexamethasone therapy on mortality and neurological recovery in stroke patients. During a sixteen month period of study, 230 patients with clinical diagnosis of stroke were seen. Of these, 40 were eligible for the study (27 were presumed to have had haemorrhagic stroke; and 13 were presumed to have had cerebral infarction). The commonest cause of exclusion was presentation after 24 hours of the ictus. Patients were sequentially paired and randomised into high dose dexamethasone and placebo groups in a double-blind fashion. There were twenty patients in either group. Of the 27 patients with haemorrhagic stroke, 15 were in the dexamethasone group and 12 in the placebo group. Of the 13 patients with cerebral infarction, 5 were in the dexamethasone group and 8 in the placebo group. Each patient received 100 mg of dexamethasone stat, and 16 mg every 6 hours for a period of 48 hours or equivalent volumes of placebo. Assessment of each patient was done using a neurological score. Sequential analysis by Armitage was employed, using survival at 1 month as the primary criterion of effectiveness. Survivors were followed-up for 6 months. At the end of one month, 16 patients (80%) had died in the dexamethasone group and 17 (85%) in the placebo group. The average day of death was six days in the dexamethasone group and 15 days in the placebo group, but this was not statistically significant. Of the seven survivors at one month, four were in the dexamethasone group and 3 in the placebo group. Five of them had cerebral infarction and two had haemorrhagic stroke. The two in the haemorrhagic subgroup who survived the first month died at the 2nd and 4th month respectively. At the end of six months, only the five patients with cerebral infarction were alive. Of these, 2 in the dexamethasone group were back at work while the third was chair-bound. The 2 survivors in the placebo group were chair and bed bound respectively. In conclusion, this study failed to demonstrate any benefit of a short-course of high dose steroid in improving the mortality of stroke patients and its use should be discouraged. However, possible benefit in the morbidity of survivors in the patients with cerebral infarction requires further studies.", "nan", "In this study with randomized controls, we administered fludrocortisone acetate to 46 of 91 patients with subarachnoid hemorrhage in an attempt to prevent excessive natriuresis and plasma volume depletion. Fludrocortisone significantly reduced the frequency of a negative sodium balance during the first 6 days (from 63% to 38%, p = 0.041). A negative sodium balance was significantly correlated with decreased plasma volume during both the first 6 days (p = 0.014) and during the entire 12-day study period (p = 0.004). Although fludrocortisone treatment tended to diminish the decrease in plasma volume, the difference was not significant (p = 0.188). More patients in the control group developed cerebral ischemia (31% vs. 22%) and, consequently, more control patients were treated with plasma volume expanders (24% vs. 15%), which may have masked the effects of fludrocortisone on plasma volume. Fludrocortisone therefore reduces natriuresis and remains of possible therapeutic benefit in the prevention of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.", "To reduce the risk of ischemic complications in patients with subarachnoid hemorrhage (SAH), hypervolemic therapy is generally advocated. However, such conventional treatment cannot always ensure the maintenance of an effective intravascular volume expansion, because excessive natriuresis and osmotic diuresis occur after SAH. In this prospective study the authors examined the effects of inhibition of natriuresis with fludrocortisone acetate on intravascular volume expansion during hypervolemic therapy.\n Thirty patients with SAH were randomized and divided into two groups: controls (Group 1, 15 patients) and patients treated with 0.3 mg/day of fludrocortisone (Group 2, 15 patients). In all patients sodium and fluid intake levels were in excess of maintenance requirements in an attempt to maintain a positive water balance and a central venous pressure (CVP) of 8 to 12 cm H2O. The mean sodium and water intake levels for 14 days after SAH were significantly reduced by fludrocortisone in Group 2 (487+/-34.52 mEq/day and 5159.2+/-249.29 ml/day, respectively; p<0.01) compared with Group 1 (634.2+/-42.86 mEq/day and 6611.7+/-365.67 ml/day). Fludrocortisone significantly reduced the urinary sodium excretion (p<0.01) and urine volume (p<0.01) in parallel, and effectively prevented a negative shift in the sodium as well as water balance (p<0.01). The serum sodium level tended to decrease in Group 1, reaching 135 mEq/L on average, but not in Group 2 (p<0.01). Hyponatremia in Group 1 was always observed at the optimal range of CVP values. A decrease in serum potassium level within the range of 2.8 to 3.5 mEq/L was transiently noted in 11 patients (73.3%) of Group 2, but was easily corrected. Possible side effects of fludrocortisone, such as pulmonary edema, were not encountered.\n Intravascular volume expansion in the presence of excessive natriuresis requires a large sodium and water intake and is often associated with hyponatremia. Inhibition of natriuresis with fludrocortisone can effectively reduce the sodium and water intake required for hypervolemia and prevent hyponatremia at the same time.", "To evaluate the efficacy of dexamethasone for treatment of primary supratentorial intracerebral hemorrhage, we studied 93 patients 40 to 80 years old, using a double-blind randomized block design. After the subjects were stratified according to their level of consciousness (Glasgow Coma Scale), those with objectively documented primary supratentorial intracerebral hemorrhage were randomly assigned to either dexamethasone or placebo. For ethical reasons, three interim analyses were planned, to permit early termination of the trial if one study group did better than the other. During the third interim analysis, the death rate at the 21st day was identical in the two groups (dexamethasone vs. placebo, 21 of 46 vs. 21 of 47; chi-square = 0.01, P = 0.93). In contrast, the rate of complications (mostly infections and complications of diabetes) was much higher in the dexamethasone group (chi-square = 10.89, P less than 0.001), leading to early termination of the study. In the light of the absence of a demonstrable beneficial effect and the presence of a significant harmful effect, current practices of using dexamethasone for treatment of primary supratentorial hemorrhage should be reconsidered." ]

[ "12149523" ]

[ "A randomised controlled crossover trial of nurse practitioner versus doctor led outpatient care in a bronchiectasis clinic." ]

[ "With the decrease in junior doctor hours, the advent of specialist registrars, and the availability of highly trained and experienced nursing personnel, the service needs of patients with chronic respiratory diseases attending routine outpatient clinics may be better provided by appropriately trained nurse practitioners.\n A randomised controlled crossover trial was used to compare nurse practitioner led care with doctor led care in a bronchiectasis outpatient clinic. Eighty patients were recruited and randomised to receive 1 year of nurse led care and 1 year of doctor led care in random order. Patients were followed up for 2 years to ensure patient safety and acceptability and to assess differences in lung function. Outcome measures were forced expiratory volume in 1 second (FEV(1)), 12 minute walk test, health related quality of life, and resource use.\n The mean difference in FEV(1) was 0.2% predicted (95% confidence interval -1.6 to 2.0%, p=0.83). There were no significant differences in the other clinical or health related quality of life measures. Nurse led care resulted in significantly increased resource use compared with doctor led care (mean difference pound 1497, 95% confidence interval pound 688 to pound 2674, p<0.001), a large part of which resulted from the number and duration of hospital admissions. The mean difference in resource use was greater in the first year ( pound 2625) than in the second year ( pound 411).\n Nurse practitioner led care for stable patients within a chronic chest clinic is safe and is as effective as doctor led care, but may use more resources." ]

[ "10091204", "10369728", "11991447", "1729617", "9026268", "8554248", "2089252", "10999778", "15465502", "3279769", "11549632", "14728632", "6346829", "18195202", "3333018", "2221645", "17243866", "16279289", "9099188", "15885294", "11918228", "12609940", "11502787", "14695863", "10841179", "16274368", "2913914", "9278463", "16283320", "6388277", "15860827", "11731184", "1331788", "16641143", "8062152", "16481635", "3035879", "9886454", "17998225", "12568412", "2740360", "17473911" ]

[ "HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial.", "Early postmenopausal bone loss is prevented by estrogen and partially by 1alpha-OH-vitamin D3: therapeutic effects of estrogen and/or 1alpha-OH-vitamin D3.", "Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study.", "Treatment of postmenopausal osteoporosis with calcitriol or calcium.", "Effects of 2 years' treatment of osteoporosis with 1 alpha-hydroxy vitamin D3 on bone mineral density and incidence of fracture: a placebo-controlled, double-blind prospective study.", "Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial.", "Effect of low-dose calcitriol and calcium therapy on bone histomorphometry and urinary calcium excretion in osteopenic women.", "Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60.", "Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study.", "Calcitriol in the treatment of postmenopausal osteoporosis.", "Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double blind, double placebo study.", "Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily.", "Calcium, vitamin D and anabolic steroid in treatment of aged bones: double-blind placebo-controlled long-term clinical trial.", "Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women.", "Long-term effect of nandrolone decanoate, 1 alpha-hydroxyvitamin D3 or intermittent calcium infusion therapy on bone mineral content, bone remodeling and fracture rate in symptomatic osteoporosis: a double-blind controlled study.", "Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. A randomized controlled study.", "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.", "Amelioration of hemiplegia-associated osteopenia more than 4 years after stroke by 1 alpha-hydroxyvitamin D3 and calcium supplementation.", "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.", "Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial.", "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.", "Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss.", "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.", "Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women.", "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.", "Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older.", "Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone mineral density in postmenopausal osteoporosis.", "Clinical, biochemical and histological results of a double-blind trial with 1,25-dihydroxyvitamin D3, estradiol and placebo in post-menopausal osteoporosis.", "Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care.", "Effects of the combined use of calcitonin and 1 alpha-hydroxycholecalciferol on vertebral bone loss and bone turnover in women with postmenopausal osteopenia and osteoporosis: a prospective study of long-term and continuous administration with low dose calcitonin.", "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.", "Effects of 1 alpha-hydroxyvitamin D3 on lumbar bone mineral density and vertebral fractures in patients with postmenopausal osteoporosis.", "Calcium plus vitamin D supplementation and the risk of fractures.", "Postmenopausal osteoporosis: no effect of three years treatment with 1,25-dihydroxycholecalciferol.", "Amelioration of osteopenia and hypovitaminosis D by 1alpha-hydroxyvitamin D3 in elderly patients with Parkinson's disease.", "Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial.", "Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial.", "The effect of calcitriol on patients with postmenopausal osteoporosis with special reference to fracture frequency.", "Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation." ]

[ "We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin (Vit) D3 supplementation in a 5-year prospective trial.\n A total of 464 early postmenopausal women, (a subgroup of the Kuopio Osteoporosis Study, n = 13,100) were randomized to four groups: (1) HRT, a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate; (2) Vit D (300 IU/day and 100 IU/day during the fifth years); (3) HRT + Vit D; and (4) placebo. Lumbar (L2-4) and femoral neck bone mineral densities (BMD) were determined by dual X-ray absorptiometry (DXA) at baseline, after 2.5 and 5 years of treatment. All new symptomatic non-vertebral, radiographically defined fractures were recorded.\n Altogether, 368 women (79%) completed the 5 year treatment. In all, 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up (HRT 4, Vit D 10, HRT + Vit D 8 and placebo 17). The reduction in the incidence of new non-vertebral fractures was significant in women with HRT alone (P = 0.032) when adjusted by baseline BMD and previous fractures; observed also with the intention-to-treat principle (P = 0.048). When the HRT groups were pooled, HRT showed a significantly lower incidence of new non-vertebral fractures (P = 0.042) than women receiving placebo and also after adjusting as above (P = 0.016); both in valid-case and in the intention-to-treat analysis. In the Vit D group, the fracture incidence was non-significantly decreased (P = 0.229) in comparison with the placebo group. The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 (95% CI, 0.10-0.90) and with Vit D 0.47 (95% CI, 0.20-1.14) and with HRT + Vit D 0.44 (95% CI, 0.17-1.15), in comparison with the placebo group (adjusted by femoral BMD and previous fractures).\n This study is the first prospective trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women. The effect of low-dose Vit D remains to be proved.", "A total of 79 Japanese women who were within 5 years of menopause were randomly assigned 1alpha-hydroxyvitamin D3 [1alpha(OH)D3] 1.0 microg/day, conjugated estrogens 0.625 mg/day, a combination of both, or control (no treatment). Lumbar spine and proximal femur bone mineral density (BMD) and biochemical indices were monitored over 2 years. In the 1alpha(OH)D3-treated group, there was a nonsignificant decrease in lumbar spine BMD compared with controls, and no significant loss in the femoral neck compared with controls. In the estrogen-treated group, there was a nonsignificant increase in spine BMD (+2.17% in the first year and +1.71% in the second year), and no loss in femoral neck BMD. The combination of conjugated estrogens +1alpha(OH)D3 was more effective in increasing BMD in the spine (+3. 68% in the first year and +3.63% in the second year) and femur (+2. 56% in the first year and +4.44% in the second year) BMD. There was a significant difference in lumbar spine BMD in both the first and second years between the combination-treated group and the 1alpha(OH)D3-treated and control groups (P < 0.01). Serum osteocalcin (OC) significantly decreased in the combination-treated group (-23.8% in the first year) and the estrogen-treated group (-37. 6% and -41.2% at 6 and 18 months, respectively), and serum alkaline phosphatase (Alp) decreased significantly in the first year in the combination-treated (-31.5%), estrogen-treated (-27.3%), and 1alpha(OH)D3-treated (-7.9%) groups, whereas serum OC increased (+45. 4% in the first year) in women without treatment. The results of this study indicate that early postmenopausal bone loss in the femoral neck is prevented by conjugated estrogens, 1alpha(OH)D3, or both, whereas bone loss in the spine is not prevented by 1alpha(OH)D3. Estrogen proves effective in preventing early postmenopausal bone loss by markedly inhibiting bone turnover. Moreover, a synergistic bone-sparing effect can be expected when estrogen is administered concomitantly with 1alpha(OH)D3 rather than when used 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.", "Osteoporosis is a common problem whose management is controversial. To evaluate the efficacy and safety of calcitriol (1,25-dihydroxyvitamin D3) in the treatment of postmenopausal osteoporosis, we conducted a three-year prospective, multicenter, single-blind study in 622 women who had one or more vertebral compression fractures. The women were randomly assigned to receive treatment with calcitriol (0.25 micrograms twice a day) or supplemental calcium (1 g of elemental calcium daily) for three years. New vertebral fractures were detected by means of lateral roentgenography of the spine each year, and calcium absorption was measured in 392 of the women.\n The women who received calcitriol had a significant reduction in the rate of new vertebral fractures during the second and third years of treatment, as compared with the women who received calcium (second year, 9.3 vs. 25.0 fractures per 100 patient-years; third year, 9.9 vs. 31.5 fractures per 100 patient-years; P less than 0.001). This effect was evident only in women who had had five or fewer vertebral fractures at base line (second year, 5.2 vs. 25.3 fractures per 100 patient-years; third year, 4.2 vs. 31.0 fractures per 100 patient-years; P less than 0.0001). The groups also differed significantly in the number of peripheral fractures; 11 such fractures occurred in 11 women in the calcitriol group, whereas 24 occurred in 22 women in the calcium group (P less than 0.05). There was no significant difference between the groups in the incidence of side effects requiring withdrawal of treatment (8.6 percent in the calcitriol group vs. 6.5 percent in the calcium group).\n Continuous treatment of postmenopausal osteoporosis with calcitriol for three years is safe and significantly reduces the rate of new vertebral fractures in women with this disorder.", "A two-year double-blind study monitored and evaluated the effects of 1 alpha-hydroxy vitamin D3 (1 alpha(OH)D3) on the lumbar (L2-4BMD) and total body bone mineral densities (TBBMD) and occurrence of fracture in 113 female osteoporotic patients receiving 0.75 micrograms/day of 1 alpha(OH)D3 (n = 57) or a placebo (n = 56) with calcium supplementation in both groups. L2-4BMD increased 1.81.% and 2.32% after one and 2 years in the 1 alpha (OH)D3 group, but decreased 1.89% (P < 0.05) and 0.28% in the placebo group. A significant difference (P < 0.01) existed between the two groups after one year. TBBMD decreased significantly in the placebo group by 3.34% (P < 0.01) and 3.52% after one and 2 years. Six new fractures occurred in the control group, but only two in the 1 alpha(OH)D3 group (Odd's ratio = 0.343, 95% confidence range; 0.0648-1.815). There were no serious adverse effects of the 1 alpha(OH)D3 treatment. It was concluded that two-year treatment with 1 alpha(OH)D3 increased the lumbar BMD and inhibited the decrease in TBBMD. Although it was not significant, new fracture occurrence in the 1 alpha(OH)D3 group was around 1/3 of that in the control group.", "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.", "We evaluated low-dose calcitriol (0.25 microgram b.i.d.) in combination with 1 g of supplemental calcium therapy as treatment for osteopenic women over 60 years of age (n = 4). Control patients (n = 6) received ergocalciferol (50,000 units twice a week) and 1 g of supplemental calcium. Bone biopsies and CT-determined bone mineral density were done initially and after 1 year of therapy. Bone mineral density increased from 77 +/- 18 to 88 +/- 9 mg/ml (NS) in the calcitriol-treated group and from 87 +/- 13 to 112 +/- 30 mg/ml (NS) in the ergocalciferol-treated group. There was also no significant change in bone volume, as determined by bone biopsy in either group. No compression fractures occurred in either treatment group. After 1 year of therapy, urinary calcium excretion was increased significantly above that observed in age-matched untreated women. Creatinine clearance did not change significantly. Hypercalcemia was rare. In summary, we found calcitriol was not superior to ergocalciferol in preventing progressive bone loss and fractures. Both therapies were associated with significant hypercalciuria.", "Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures. A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites, bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a randomized, double-blind, placebo-controlled trial. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone structure by radiographs. Calcium biochemistry and bone turnover markers were measured in blood and urine. The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr. Baseline median calcium intake was 546 mg/day, and median serum 25OH vitamin D3 was 59 nmol/L. On placebo, loss of BMD at total hip was 2% and femoral medulla expansion was 3% over 4 yr. Calcium reduced bone loss, secondary hyperparathyroidism, and bone turnover. 25OH vitamin D3 was intermediate between placebo and calcium. Fracture rates and drop-out rates were similar among groups, and there were no serious adverse events with either supplement. A calcium supplement of 750 mg/day prevents loss of BMD, reduces femoral medullary expansion, secondary hyperparathyroidism, and high bone turnover. A supplement of 15 microg/day 25OH vitamin D3 is less effective, and because its effects are seen only at low calcium intakes, suggests that its beneficial effect is to reverse calcium insufficiency.", "To assess the comparative effectiveness of several medications on bone mineral density, biochemical bone markers, and the incidence of vertebral fractures in postmenopausal women with osteoporosis.\n A total of 396 postmenopausal women, aged 50 to 75 years, were allocated randomly to six equal-sized groups: hormone replacement therapy, etidronate, eel calcitonin, alfacalcidol, vitamin K (menatetrenone), or control (no treatment). Thoracic and lumbar spine radiographs, bone mineral density at the distal radius, and markers of bone turnover were assessed at baseline and every 3 months during the 2-year study.\n Compared with baseline, the 2-year mean changes in bone mineral density were 2.0% for hormone replacement therapy, -0.5% for etidronate, 1.6% for calcitonin, -3.6% for alfacalcidol, -1.9% for vitamin K, and -3.3% for control. Seventeen (26%) of the 66 control patients developed new vertebral fractures. Compared with controls, the relative risks of vertebral fracture were 0.35 (95% confidence interval [CI]: 0.14 to 0.83) for hormone replacement therapy, 0.40 (95% CI: 0.17 to 0.92) for etidronate, 0.41 (95% CI: 0.17 to 0.93) for calcitonin, 0.56 (95% CI: 0.26 to 1.12) for alfacalcidol, and 0.44 (95% CI: 0.20 to 0.99) for vitamin K.\n We observed significant reductions in the incidence of vertebral fractures with hormone replacement therapy, etidronate, and calcitonin, and significant improvements in bone mineral density with hormone replacement therapy and calcitonin.", "Calcitriol was compared with placebo in the treatment of postmenopausal osteoporosis in a double-blind, randomized, parallel clinical trial of 24 months' duration. Adjustment was made in dietary calcium to maximize the dose of calcitriol. The study was completed by 15 patients who received placebo and 12 patients who received calcitriol. The calcitriol group had positive slopes (compared with negative slopes for the placebo group) for total body calcium, bone mineral content of the radius, bone mineral density of the lumbar spine, and radiographic absorptiometry of the middle phalanges. The difference between the two groups was statistically significant for each of these measurements. The fracture rate in the treatment group was 250 per 1,000 patient-years as compared with 333 for the placebo group. The mean dose of calcitriol was 0.8 micrograms per day. Hypercalcemia, hypercalciuria, and perhaps nephrolithiasis were observed as complications of treatment. Calcitriol increased bone mineral density by decreasing bone resorption, but not by increasing bone formation. Future studies should concentrate on treatment with oral calcitriol in lower doses. It would also be of interest to examine parenteral administration of calcitriol. It is possible that bone formation can be increased by achieving higher serum levels of the drug, whereas complications may be avoided by using a non-oral route of administration.", "Osteoporosis in men is an emerging public health problem. As calcitriol reduces the rate of vertebral fractures in osteoporotic postmenopausal women, we conducted a prospective study of this treatment in men with primary osteoporosis. Our study was a 2-yr, randomized, double masked, double placebo-controlled trial of calcitriol (0.25 microg twice daily) or calcium (500 mg twice daily) in 41 men with primary osteoporosis and at least 1 baseline fragility fracture. Thirty-three men (85%) completed the study. There were no differences in baseline characteristics. Spinal and femoral neck bone mineral densities at 2 yr were unchanged in both groups. Serum osteocalcin decreased in both groups by 30% (P < 0.05), whereas urine N-telopeptide cross-links decreased only in the calcium group by 30% (P < 0.05). After 2 yr, fractional calcium absorption increased by 34% (P < 0.01) in the calcitriol group. Nineteen incident fragility fractures occurred (14 vertebral and 5 nonvertebral) in 7 men. Over 2 yr, the number of men with vertebral fractures (6 vs. 1; P = 0.097) was similar in both groups. In conclusion, the efficacy of calcitriol remains unproven as a single agent for the treatment of osteoporosis in men.", "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.", "In a double-blind trial, 327 patients (57 men) over 65 (mean age 79.5) years received all possible combinations of calcium carbonate 3 g, vitamin D3 1000 iu, methandienone 2.5 mg and/or placebos daily for 9 months. The higher incidence of bone fractures in the placebo group was not significant. Serum calcium, phosphorus, creatinine, aspartate aminotransferase and alkaline phosphatase were followed: the greatest changes occurred with methandienone, which thus reduced osteoporotic activity and increased the muscular mass most effectively; calcium carbonate had the poorest effect. Surprisingly, coronary mortality was higher among those taking all three active substances. With two treatments the increase was not significant, but when both the groups receiving a combination of any two of the treatments were compared with those taking only one or neither of these two treatments, a significant increase in coronary deaths was seen, most significant (P less than 0.001) in those receiving vitamin D3 and methandienone.", "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.", "A double-blind controlled study was performed in 60 patients with symptomatic osteoporosis with at least one vertebral crush fracture, comparing the effect of nandrolone decanoate, 1 alpha-hydroxyvitamin D3 and intermittent calcium infusions. Thirty-four out of 60 patients completed the 2 year observation period. Nandrolone decanoate statistically significantly increased the bone mineral content at the radius, reduced the endosteal bone loss at the metacarpals and statistically significantly reduced urinary calcium and hydroxyproline excretion. Calcium infusions and 1 alpha-hydroxyvitamin D3 inhibited further loss of bone mineral content, but endosteal bone loss continued. In the second year fracture rate was reduced in the nandrolone decanoate groups compared to the two other groups. We conclude that nandrolone decanoate is an active drug for increasing bone mineral content and reducing endosteal bone loss, while 1 alpha-hydroxyvitamin D3 and calcium infusions only stop further bone mineral loss at the radius but do not inhibit endosteal bone loss as measured at the metacarpals and that single photon absorptiometry and radiography are complementary in interpreting cortical bone mineral changes.", "To study the efficacy of synthetic 1,25 dihydroxyvitamin D3 (calcitriol) in the treatment of osteoporosis.\n Two-year, double-blind, randomized clinical trial.\n University medical center.\n Fifty postmenopausal women with vertebral fractures recruited by referral.\n Calcium intake was adjusted to 25 mmol/d (1000 mg/d) at baseline. Patients were then randomized to treatment with either calcitriol or placebo. During the study, calcium intake was reduced to 15 mmol/d (600 mg/d) and the dose of calcitriol was adjusted to maintain serum calcium less than 2.74 mmol/L (less than 11.0 mg/dL) or urine calcium less than 9.96 mmol/d (less than 400 mg/d).\n After 2 years, the mean dose of calcitriol in the treated group was 0.62 micrograms/d. Bone mineral density of the spine increased 1.94% with calcitriol therapy and decreased 3.92% with placebo (P = 0.001). Total body calcium increased 0.21% with calcitriol therapy and decreased 1.85% with placebo (P = 0.004). Patients receiving placebo had significant decreases in spine density (P = 0.0007) and total body calcium (P = 0.0004). There were no differences in vertebral fracture rates between the groups. Renal function studies were not statistically different between the groups after 2 years.\n The treatment of postmenopausal osteoporotic women with synthetic calcitriol for 2 years was associated with increases in spine density and total body calcium. No adverse effects on renal function were seen after long-term calcitriol therapy.", "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.", "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.", "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.", "Randomized controlled trials have shown that a combination of vitamin D and calcium can prevent fragility fractures in the elderly. Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known. We studied if an intervention with 10 microg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double-blinded randomized controlled trial. Residents from 51 nursing homes were allocated randomly to receive 5 ml of ordinary cod liver oil (n = 569) or 5 ml of cod liver oil where vitamin D was removed (n = 575). During the study period of 2 years, fractures and deaths were registered, and the principal analysis was performed on the intention-to-treat basis. Biochemical markers were measured at baseline and after 1 year in a subsample. Forty-seven persons in the control group and 50 persons in the vitamin D group suffered a hip fracture. The corresponding figures for all nonvertebral fractures were 76 persons (control group) and 69 persons (vitamin D group). There was no difference in the incidence of hip fracture (p = 0.66, log-rank test), or in the incidence of all nonvertebral fractures (p = 0.60, log-rank test) in the vitamin D group compared with the control group. Compared with the control group, persons in the vitamin D group increased their serum 25-hydroxyvitamin D concentration with 22 nmol/liter (p = 0.001). In conclusion, we found that an intervention with 10 microg of vitamin D3 alone produced no fracture-preventing effect in a nursing home population of frail elderly people.", "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.", "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.", "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.", "Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.", "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.", "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 a randomized multicenter, double-blind, double-dummy, parallel group study a comparison of the efficacy and safety of 1 microg alfacalcidol to 880 IU vitamin D plus calcium carbonate (1 g calcium) once daily per os was performed on 148 postmenopausal osteoporotic Caucasian patients with normal vitamin D serum levels for 18 months. Bone mineral density (BMD) was measured at baseline, 12 and 18 months. Safety parameters were followed during the entire study period. Sixty-nine (90.8%) in the alfacalcidol group and 67 (93.1%) in the vitamin D group were included in the ITT analysis. Lumbar BMD in the alfacalcidol group increased by 0.017 g/cm2 (2.33%) and 0.021 g/cm2 (2.87%) from baseline (P<0.001) at 12 and 18 months, respectively, whereas in the vitamin D plus calcium group the increase was 0.005 g/cm2 (0.70%) from baseline (N.S.) at both 12 and 18 months. The higher changes from baseline in the alfacalcidol group, as compared to the changes in the vitamin D plus calcium group at both 12 and 18 months, were found to be statistically significant (P=0.018, 0.005). A small increase of mean femoral BMD was achieved in both groups (N.S.). Adverse events were similar in both groups. No significant differences were noted between the groups in serum calcium. In conclusion, alfacalcidol was found to be superior in significantly increasing lumbar BMD as compared to vitamin D plus calcium while safety characteristics were found to be similar in both treatments.", "Twenty-eight women with postmenopausal osteoporosis were studied in a double-blind trial aimed to compare the effects of a one-year treatment with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), estradiol valerate (E2) and placebo. Patients were divided into 4 groups: group 1 was given 1,25(OH)2D3 alone, group 2 was given E2 alone, group 3 was given 1,25(OH)2D3 + E2, group 4 received a placebo. The evaluation of the effects of the treatments included clinical examination of patients, the measurement of a number of biochemical parameters, such as plasma and urinary calcium and phosphate, urinary hydroxyproline, serum alkaline phosphatase, the measurement of intestinal calcium absorption and bone mineral content (BMC) and a histomorphometric study of bone biopsies from the iliac crest. The best clinical results were obtained in the patients who were given 1,25(OH)2D3 alone; appreciable results were also noticed in the patients who were given E2 alone or in combination with 1,25(OH)2D3, while patients in the placebo group worsened. BMC decreased in the placebo group and increased, although non significantly, in the patients treated with 1,25(OH)2D3 or E2 or both. The histomorphometric study showed a significant increase in the mean trabecular diameter in patients treated with 1,25(OH)2D3 alone or in combination with E2. Changes in the volume density of trabecular bone paralleled those in BMC. The results of the trial indicate that 1,25(OH)2D3 is an effective therapeutic agent in postmenopausal osteoporosis.", "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.", "The present study investigates the effect of long-term and continuous treatment with low dose calcitonin in combination with 1 alpha-hydroxycholecalciferol on vertebral bone mass in early postmenopausal women.\n A total of 202 postmenopausal women between 53 and 58 years of age were recruited individually and randomly assigned to one of four groups. Comparisons were made among groups of women receiving calcitonin alone (10 IU i.m. twice a month), 1 alpha-hydroxycholecalciferol alone (0.5 microg orally twice daily), a combination of the above two agents, or no treatment. Bone mineral density (BMD) of lumber spine (L2-4) was determined using Dual Energy X-ray Absorptiometry. The study was carried out prospectively over a 2-year period.\n We observed a significant increase in vertebral bone mass in the combined treatment regimen of calcitonin and 1 alpha-hydroxycholecalciferol (3.44% at 12 months in the combination group vs 1.40,0.92, and -0.70% in the calcitonin alone, 1 alpha-hydroxycholecalciferol alone, and control groups, respectively; 4.51% at 24 months in the combination group vs 2.21,1.04, and -3.61% in the calcitonin alone, 1 alpha-hydroxycholecalciferol alone, and control groups, respectively). Serum PTH, osteocalcin levels and alkaline phosphatase activity decreased significantly within 12 months whereas urinary pyridinoline/creatinine ratio decreased at 24 months in the combination group. We observed mild adverse effects in 25.0% (7/28) and 30.0% (6/20) of combination regimen and calcitonin treatment cases, respectively.\n The results of the study suggest that the combination treatment regimen increased vertebral bone loss in early postmenopausal women to a greater extent than did calcitonin alone or 1 alpha-hydroxycholecalciferol alone.", "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.", "The effects of 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] on bone mineral density, fracture incidence, and bone metabolism were evaluated by a double-blind, placebo-controlled study. Eighty postmenopausal osteoporotic Japanese women (71.9 +/- 7.3 years, mean +/- SD) were randomly assigned to 1 microgram of 1 alpha(OH)D3 daily or inactive placebo for 1 year. All patients were given supplemental calcium (300 mg of elemental calcium daily). Lumbar (L2-L4) bone mineral density (BMD) determined by dual energy X-ray absorptiometry increased 0.65% with 1 alpha(OH)D3 treatment and decreased 1.14% with placebo (P = 0.037). BMD in both the femoral neck and Ward's triangle did not yield any significant differences between the two groups, whereas trochanter BMD in the 1 alpha(OH)D3-treated group increased 4.20% and decreased 2.37% with placebo (P = 0.055). X-ray analysis demonstrated that new vertebral fractures occurred in two patients with 1 alpha(OH)D3 and in seven patients with placebo. The vertebral fracture rate in the treated group was significantly less (75/1000 patient years) than in the control group (277/1000 patient years; P = 0.029). Hypercalcemia (12.1 mg/100 ml) occurred in one patient receiving 1 alpha(OH)D3; however, the serum calcium level in this patient promptly decreased to the reference range after cessation of the treatment. There were no significant changes in serum creatinine level in either group. A significant increase in urinary excretion of calcium was found but there was no significant change in urinary excretion of hydroxyproline in the treated group. The serum level of bone-derived alkaline phosphatase activity significantly decreased by -26 +/- 26 (mU/ml) after the treatment (P = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)", "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", "The therapeutic effect of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) in postmenopausal osteoporosis was tested in a single blind, randomized prospective study. Thirty-nine women, 50-65 years of age, were treated for three years with 0.5 microgram 1,25(OH)2D3 daily. In a control group, 37 women were given 400 IU vitamin D3 daily. There was no significant difference in annual bone loss from the distal or proximal forearm between the groups. New vertebral fractures were evaluated, and in the treatment group, the annual increase in vertebral fractures was 0.18 +/- 0.387 and in the control group 0.13 +/- 0.330. New long bone fractures were 7 and 5, respectively. None of the observed differences were statistically significant. In the 1,25(OH)2D3 group, 28% had to reduce the dose because of slight hypercalcaemia. We conclude that 1,25(OH)2D3 as used in this study is not effective in the treatment of osteoporosis.", "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.", "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.", "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.", "nan", "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." ]

[ "2781235", "10406187", "7811344", "8679834" ]

[ "Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease.", "S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial.", "Effect of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver disease.", "[Parenteral S-adenosylmethionine compared to placebos in the treatment of alcoholic liver diseases]." ]

[ "S-Adenosyl-L-methionine (SAMe) is a physiologic precursor of thiols and sulfurated compounds, which are known to be decreased in patients with liver disease. The effect of its administration on the hepatic glutathione content of liver patients was investigated. Four groups of subjects were selected: a) 9 patients with alcoholic liver disease treated with SAMe (1.2 g/day orally for 6 months); b) 7 patients with non-alcoholic liver disease treated as above; c) 8 placebo-treated patients with alcoholic liver disease; and d) 15 normal subjects as a control group. Total and oxidized glutathione were assayed by high-performance liquid chromatography of liver biopsy specimens before and after the treatment period. In all patients pre-treatment hepatic glutathione was significantly decreased as compared with controls. SAMe therapy resulted in a significant increase of hepatic glutathione levels both in patients with alcoholic and in those with non-alcoholic liver diseases as compared with placebo-treated patients. SAMe may therefore exert an important role in reversing hepatic glutathione depletion in patients with liver disease.", "The efficacy of S-adenosylmethionine (AdoMet) in the treatment of liver cell injury has been demonstrated in several experimental models. The aim of this study was to investigate the effects of AdoMet treatment in human alcoholic liver cirrhosis.\n A randomized, double-blind trial was performed in 123 patients treated with AdoMet (1200 mg/day, orally) or placebo for 2 years. All patients had alcoholic cirrhosis, and histologic confirmation of the diagnosis was available in 84% of the cases. Seventy-five patients were in Child class A, 40 in class B, and 8 in class C. Sixty-two patients received AdoMet and 61 received placebo.\n At inclusion into the trial no significant differences were observed between the two groups with respect to sex, age, previous episodes of major complications of cirrhosis, Child classification and liver function tests. The overall mortality/liver transplantation at the end of the trial decreased from 30% in the placebo group to 16% in the AdoMet group, although the difference was not statistically significant (p = 0.077). When patients in Child C class were excluded from the analysis, the overall mortality/liver transplantation was significantly greater in the placebo group than in the AdoMet group (29% vs. 12%, p = 0.025), and differences between the two groups in the 2-year survival curves (defined as the time to death or liver transplantation) were also statistically significant (p = 0.046).\n The present results indicate that long-term treatment with AdoMet may improve survival or delay liver transplantation in patients with alcoholic liver cirrhosis, especially in those with less advanced liver disease.", "We measured glutathione and cysteine concentrations in erythrocytes of chronic alcohol misusers with (20 subjects) and without liver cirrhosis (20 subjects). Glutathione levels were decreased, whereas those of cysteine were increased in all patients. Parenteral treatment with S-adenosylmethionine (SAME); (2 g daily in 250 ml 0.15 M NaCl for 15 days) corrected the erythrocyte thiol alterations. We conclude that parenteral treatment with SAME affects the metabolism of SH compounds in erythrocytes of alcoholic patients.", "The improvements in the knowledge of the action of ethanol over the hepatic cell, its direct action over the cell, and the intracytoplasmatic structures membranes, point out the possibilities of use of sulfo-adenosil-L-metionina (SAMe); as an util drug inn the treatment of the altered metilation reactions, that take place in those membranes, facilitating their physiological functions. The primary end point in this study was to demonstrate the therapeutic worth os SAMe, by parenteral route in 45 patients with alcoholic liver disease, which were determined by clinical laboratory and hepatic function test, label qith 32 points or more of the discriminatory function index. Divided into two groups, placebo-SAMe, randomized, double blind. As well as total plasmatic and reduced glutation and lipoperoxidation index, indirect form as malondehaldehyde. Were determined at the first visit anf after 8 and 15 days of treatment. Comparing the results of both groups there were a significative favorable results for the group treatment with SAMe and this confirms the utility of this drug in the treatment of patients with alcoholic liver disease with a discriminatory function index (Maddrey index), of 32 points or more." ]

[ "3314832" ]

[ "Does colchicine work? The results of the first controlled study in acute gout." ]

[ "We have performed the first controlled study of colchicine in acute gout, to determine its efficacy and toxicity, and to define the natural history of acute gout. Two-thirds of colchicine-treated patients improved after 48 hours, but only one-third of the patients receiving placebo demonstrated similar improvement. The colchicine-treated patients responded earlier; significant differences from placebo were shown after 18-30 hours. All patients given colchicine developed diarrhea after a median time of 24 hours (mean dose of colchicine 6.7 mg). This side effect occurred before relief of pain in most patients." ]

[ "12584485", "15213581", "9337494", "1770187", "17667482", "12611031", "20673557", "7217537", "16972117" ]

[ "Enhancing behavioral and social skill functioning in children newly diagnosed with attention-deficit hyperactivity disorder in a pediatric setting.", "Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment.", "Social skills training with parent generalization: treatment effects for children with attention deficit disorder.", "Effects of a school-based cognitive-behavioral intervention for ADHD children.", "A randomized, controlled trial of integrated home-school behavioral treatment for ADHD, predominantly inattentive type.", "Social skills training in children with attention deficit hyperactivity disorder: a randomized-controlled clinical trial.", "Effects of atomoxetine with and without behavior therapy on the school and home functioning of children with attention-deficit/hyperactivity disorder.", "Evaluation of the relative effectiveness of methylphenidate and cognitive behavior modification in the treatment of kindergarten-aged hyperactive children.", "Does brief, clinically based, intensive multimodal behavior therapy enhance the effects of methylphenidate in children with ADHD?" ]

[ "The objective of this study was to evaluate the effectiveness of an 8-week behavioral and social skill (BSS) class for children newly diagnosed with attention-deficit hyperactivity disorder (ADHD) and their parents, initiating stimulant treatment in primary care. The subjects were 100 children, aged 5 to 12 years, recently diagnosed with ADHD and treated with stimulant medication, and their parents or guardians. Eligible families were randomly assigned to an intervention group (IG: n = 59) or control group (CG: n = 41). The BSS function of each child was assessed using DuPaul's ADHD Parent Rating Scale (18-item) and Child Attention Profile (12-item) during blinded baseline and follow-up interviews. Parent discipline practice was assessed using a five-item inventory based on Likert-scale ratings during identical periods. Computerized pharmacy records were used to track psychostimulant use over time. IG children exhibited significantly lower parent-rated ADHD symptoms, whereas IG parents reported significantly better and more consistent discipline practices compared with CG parents across time. No significant differences were found between groups in Child Attention Profile scores across time. Psychostimulant use did not significantly differ between groups across time. BSS training was well accepted and seemed to significantly improve BSS functioning among IG children in the home setting only.", "To test the hypotheses that in children with attention-deficit/hyperactivity disorder (ADHD) (1) symptoms of ADHD, oppositional defiant disorder, and overall functioning are significantly improved by methylphenidate combined with intensive multimodal psychosocial treatment compared with methylphenidate alone and with methylphenidate plus attention control and (2) more children receiving combined treatment can be taken off methylphenidate.\n One hundred three children with ADHD (ages 7-9), free of conduct and learning disorders, who responded to short-term methylphenidate were randomized for 2 years to (1) methylphenidate alone; (2) methylphenidate plus psychosocial treatment that included parent training and counseling, social skills training, psychotherapy, and academic assistance, or (3) methylphenidate plus attention psychosocial control treatment. Assessments included parent, teacher, and psychiatrist ratings, and observations in academic and gym classes.\n Combination treatment did not lead to superior functioning and did not facilitate methylphenidate discontinuation. Significant improvement occurred across all treatments and continued over 2 years.\n In stimulant-responsive children with ADHD, there is no support for adding ambitious long-term psychosocial intervention to improve ADHD and oppositional defiant disorder symptoms. Significant benefits from methylphenidate were stable over 2 years.\n Copyright 2004 American Academy of Child and Adolescent Psychiatry", "The effectiveness of brief social skills training (SST) was evaluated in a controlled outcome study with 27 children meeting criteria of the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised; American Psychiatric Association, 1987) for an attention deficit disorder. Children were randomly assigned to either SST with parent-mediated generalization (SST-PG), child-only SST, or a wait-list control group. SST consisted of 8 group sessions in which skill modules were taught sequentially. Parents of children in the SST-PG group simultaneously participated in group generalization training designed to support their children's transfer of skills. Significant improvement in children's skill knowledge and in parent reports of social skills and disruptive behavior occurred for both treatment groups relative to the wait-list control group and maintained at a 4-month follow-up. More modest evidence was found for generalization of SST to the school setting.", "Two variations of school-based cognitive-behavioral training (CBT) program were compared to each other and to a waiting-list control condition in the treatment of children with attention-deficit hyperactivity disorder (ADHD). The experimental interventions included a multicomponent condition that provided coordinated training programs for parents, teachers, and children and a teacher-only condition that offered training for classroom teachers only. Evaluation of outcome occurred at pre-intervention, post-intervention and at 6-week followup periods. Depedent measures included classroom behavior observations, teacher ratings of child behavior, child self-report, and teacher ratings of adjustment. The multicomponent CBT condition was significantly better than the other conditions at improving observed off-task/disruptive behavior at post-test. This improvement was maintained at followup, although treatment condition differences were no longer significant. There were no treatment condition differences on any other measures at post-intervention or followup. It was concluded that the intervention had minimal short-term effects on the ADHD children. The results are discussed within the context of several methodological limitations of the study which serve as proposals for continued research in this area.", "To evaluate the efficacy of a behavioral psychosocial treatment integrated across home and school (Child Life and Attention Skills Program) with attention-deficit/hyperactivity disorder (ADHD) predominantly inattentive type (ADHD-I).\n Sixty-nine children ages 7 to 11 years were randomized to the Child Life and Attention Skills Program or a control group who did not receive the intervention. We compared groups posttreatment and at 3- to 5-month follow-up on parent and teacher ratings of inattention, sluggish cognitive tempo, and functional impairment.\n Children randomized to the Child Life and Attention Skills Program were reported to have significantly fewer inattention and sluggish cognitive tempo symptoms, and significantly improved social and organizational skills, relative to the control group. Gains were maintained at follow-up.\n Behavioral psychosocial treatment, when specifically adapted for ADHD-I and coordinated among parents, teachers, and children, appears efficacious in reducing symptoms and impairment associated with ADHD-I.", "Evaluated efficacy of social skills training (SST) on children with 2 subtypes of attention deficit hyperactivity disorder (ADHD). Participants were 120 children (30 girls, 90 boys), ages 8 to 12 with ADHD-Inattentive type (ADHD-I; n = 59) or Combined type (ADHD-C; n = 61). The children were randomly assigned within diagnosis subtype to the treatment condition (8 weeks of SST) or the no-intervention control condition. SST led to greater improvements in both parent- and child-perceived assertion skills in the children with ADHD, yet did not affect the other domains of social competence. Diagnostically heterogeneous groups led to greater improvements on parent-report of their child's cooperation and assertion abilities as well as children's report of their own empathy skills. Diagnostically homogeneous groups led to greater decreases in externalizing behaviors at posttreatment but not at follow-up. Children with comorbid oppositional defiant disorder (ODD) did not benefit as much from the intervention. Children with ADHD-I improved in assertion skills more than children with ADHD-C, yet the 2 diagnostic entities did not differ in improvement levels across all other social skills.", "To evaluate the effects of atomoxetine alone and in combination with behavior therapy on the school functioning of children with attention-deficit/hyperactivity disorder (ADHD). Most atomoxetine studies have not assessed school functioning other than by measuring the change in ADHD symptoms. Combining behavior therapy with atomoxetine may be particularly beneficial for the academic domain as medication has not been found to produce sustained benefits in this realm. However, there is little research examining the effects of combining atomoxetine and behavior therapy.\n In an 8-week open-label trial, 56 children aged 6-12 years with ADHD diagnosed according to DSM-IV-TR were randomly assigned to receive atomoxetine and behavior therapy or atomoxetine alone. Behavior therapy consisted of an 8-week parenting course, a child social skills course, and a teacher-implemented daily report card of classroom behavior. The primary outcome was direct observation of the subject's classroom behavior. Secondary outcomes included change in ADHD symptoms and functioning at home and school. All data were collected between March 2007 and May 2008.\n Classroom observations showed that atomoxetine decreased rule violations (P < .0001). Moreover, atomoxetine was associated with significant improvements in ADHD and oppositional defiant disorder symptoms at home and school and enhanced functioning in both domains (Impairment Rating Scale: all P < .001). Combined treatment led to greater improvements in parent-rated symptoms of inattention (P < .01), problem behaviors (P < .001), and academic impairment (P < .05). However, teachers did not report significant group differences.\n Atomoxetine improved ADHD symptoms and classroom functioning as measured by parents, teachers, and direct observation. The addition of behavior therapy led to further improvements at home but not at school.\n clinicaltrials.gov Identifier: NCT00918567.\n © Copyright 2010 Physicians Postgraduate Press, Inc.", "This study of kindergarten-aged hyperactive children evaluated the effects of three modes of treatment in relation to an untreated control group. The treatments were administered over a 3-month period and included cognitive behavior modification, methylphenidate, and the two treatments combined. A follow-up assessment was done approximately 1 year later at the end of the first grade. Analyses of psychological, rating scale observational, and interview data showed that hyperactive children became less symptomatic over time; the data did not provide evidence indicating that any of the treatments studied was more effective than any other or than no treatment at all.", "The additional value of a short-term, clinically based, intensive multimodal behavior therapy to optimally titrated methylphenidate in children with attention-deficit hyperactivity disorder (ADHD) was investigated.\n Fifty children with ADHD (ages 8-12) were randomized to treatment of methylphenidate or treatment with methylphenidate combined with 10 weeks of multimodal behavior therapy. The multimodal behavior therapy consisted of a child and parent behavioral therapy and a teacher behavioral training. Assessments included parent, teacher and child ratings of ADHD symptoms, oppositional and conduct behavior, social skills, parenting stress, anxiety and self-worth.\n Both treatment conditions yielded significant improvements on all outcome domains. No significant differences were found between both treatments.\n No evidence was found for the additive effect of multimodal behavior therapy next to optimally titrated methylphenidate.\n This study does not support the expectation that optimally dosed stimulant treated children with ADHD should routinely receive psychosocial treatment to further reduce ADHD- and related symptoms." ]

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[ "Injectable ketoprofen vs. acetylsalicylic acid for the relief of severe cancer pain: a double-blind, crossover trial.", "Nimesulide and diclofenac in the control of cancer-related pain. Comparison between oral and rectal administration.", "Naproxen sodium in treatment of bone pain due to metastatic cancer.", "[Clinical testing of a new analgesic combination on cancer patients in chronic pain].", "Flurbiprofen for the treatment of bone pain in patients with metastatic breast cancer.", "Efficacy and tolerance of oral dipyrone versus oral morphine for cancer pain.", "Analgesic efficacy of ketoprofen in postpartum, general surgery, and chronic cancer pain.", "Aspirin and pancreatic cancer pain.", "Ketorolac, a new non-opioid analgesic: a double-blind trial versus pentazocine in cancer pain.", "A double-blind study comparing two single-dose regimens of ketorolac with diclofenac in pain due to cancer.", "Double-blind evaluation of short-term analgesic efficacy of orally administered diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic cancer pain.", "A double-blind evaluation of the analgesic efficacy and toxicity of oral ketorolac and diclofenac in cancer pain. The TD/10 recordati Protocol Study Group.", "Combination therapy with ibuprofen and methadone for chronic cancer pain.", "Medical therapy of malignant nerve pain. A randomised double-blind explanatory trial with naproxen versus slow-release morphine.", "Ketorolac versus diclofenac sodium in cancer pain.", "The dose-response relationship of controlled-release codeine (Codeine Contin) in chronic cancer pain.", "Comparison of morphine and ketorolac for intravenous patient-controlled analgesia in postoperative cancer patients.", "The efficacy of choline magnesium trisalicylate (CMT) in the management of metastatic bone pain: a pilot study.", "Naproxen versus aspirin as analgesics in advanced malignant disease.", "Morphine-sparing effect of diclofenac in cancer pain.", "Sodium naproxen versus sodium diclofenac in cancer pain control.", "Non-steroidal anti-inflammatory drugs as the first step in cancer pain therapy: double-blind, within-patient study comparing nine drugs.", "A double-blind parallel evaluation of the efficacy and safety of a single dose of ketoprofen in cancer pain.", "A comparison of two nonsteroidal antiinflammatory drugs (diflunisal versus dipyrone) in the treatment of moderate to severe cancer pain: a randomized crossover study.", "Ketorolac tromethamine in cancer pain.", "A double-blind study with placebo control of intramuscular ketorolac tromethamine in the treatment of cancer pain.", "A multiinstitutional evaluation of the analgesic efficacy and safety of ketorolac tromethamine, acetaminophen plus codeine, and placebo in cancer pain.", "[Drug therapy in severe tumor pain. Comparative study of a new combination preparation versus diclofenac-Na].", "Nimesulide in the treatment of advanced cancer pain. Double-blind comparison with naproxen.", "Comparison of piroxicam and acetylsalicylic acid for pain in head and neck cancers: a double-blind study.", "Double-blind evaluation of analgesic efficacy of orally administered diclofenac, nefopam, and acetylsalicylic acid (ASA) plus codeine in chronic cancer pain.", "Analgesia with oral narcotics and added ibuprofen in cancer patients." ]

[ "Thirty-six patients suffering from severe pain due to bone involvement from cancer participated in an analgesic study that compared single doses of ketoprofen 100 or 400 mg iv or injectable acetylsalicylic acid 1 g. A double-blind, balanced incomplete block design was adopted, in which each patient received two of the three test treatments, with an interval of 24 hours. Ketoprofen 400 mg proved significantly superior to 100 mg of the same drug, and was superior to 1 g of the acetylsalicylic acid derivative in the patients' assessment of the overall response. This was expressed by a visual analog scale and preferences. No adverse reaction was observed with any treatment.", "64 patients with pain associated with advanced cancer were treated with either nimesulide or diclofenac as initial analgesia. Patients were randomly allocated to 1 of 4 treatment groups: oral nimesulide 300 mg/day; oral diclofenac 150 mg/day; rectal nimesulide 400 mg/day; and rectal diclofenac 200 mg/day. After 1 week of treatment, both drugs provided an adequate degree of pain relief and allowed an increase in sleep duration. There were no significant differences in efficacy between the drugs or routes of administration. Fewer side effects were observed with nimesulide, giving this agent a better therapeutic index than the reference compound.", "This multicenter, double-blind, randomized, parallel study compared the efficacy and safety of two dosages of naproxen sodium (NS) in 100 patients with bone pain due to metastatic cancer. Patients were asked to rate their pain on a scale of 0-99; those patients with pain scores of 40 or more (indicating moderate to severe pain) were enrolled. Patients receiving the high-dosage regimen (HDR; n = 51) received NS 550 mg every 8 h for 3 days. Those receiving the low-dosage regimen (LDR; n = 49) received on day 1 an initial dose of NS 550 mg followed by NS 275 mg capsules every 8 h through day 3. Patients evaluated pain intensity 8 times/day. During use of NS, pain intensity scores decreased by approximately one-third in each treatment group. Among patients who responded to NS, pain relief with the HDR was significantly greater than with the LDR. Differences between regimens in adverse events during treatment were non-significant; complaints were mainly gastrointestinal and mild.", "nan", "Two investigators enrolled 26 women with metastatic breast carcinoma in a six-week, double-blind, placebo-controlled, crossover study of flurbiprofen (Ansaid, Upjohn) and placebo. The study was designed to determine the efficacy of flurbiprofen in reducing bone pain due to metastatic breast cancer. Pain score, overall performance, and concomitant use of narcotics were evaluated. The overall mean differences in pain scores between flurbiprofen and placebo showed better control of pain during treatment with flurbiprofen. None of these differences approached statistical significance. Evaluation of overall performance status reached statistical significance in one investigator's group. Three out of four patients reported decreased consumption of acetaminophen/aspirin plus codeine combinations while receiving flurbiprofen.", "In a double-blind, randomised and parallel clinical trial, two oral doses of dipyrone (1 and 2 g) administered every 8 h were compared with 10 mg of oral morphine given every 4 h for the relief of chronic cancer pain. A total of 121 patients with cancer pain without gastric involvement participated in a 7-day treatment course and were allocated to receive either dipyrone 1 g (n = 41), dipyrone 2 g (n = 38) or morphine (n = 42). Drug efficacy was analysed according to the degree of pain relief using a 100-mm visual analogue scale, and the number of patients who decided to increase the dose of the analgesic drug on day 4. The analgesic effect of dipyrone, 2 g every 8 h, was similar to that of morphine. The efficacy of both schedules was significantly greater than that of dipyrone, 1 g every 8 h. Dipyrone at either 1 or 2 g doses tended to be better tolerated than morphine, although the differences were not statistically significant.", "This article summarizes the results of five single-dose clinical studies of three pain models: postpartum, postoperative, and chronic cancer pain. The efficacy of ketoprofen (in varying doses from 25 to 225 mg) was compared with one of the following standards: aspirin (650 mg), codeine (90 mg), acetaminophen (650 mg) plus codeine (60 mg), and parenteral morphine (5 mg and 10 mg). The results indicate that ketoprofen in doses as low as 25 mg has analgesic properties significantly superior to those of placebo. For the treatment of postpartum pain, ketoprofen was significantly more effective than aspirin 650 mg but not significantly different from codeine 90 mg. Ketoprofen doses of 50 mg and 150 mg also provided analgesia superior to that with acetaminophen 650 mg plus codeine 60 mg for the management of moderate to severe postoperative pain. Moreover, oral doses of ketoprofen (75 and 225 mg) provided analgesia similar to that obtained with 5 and 10 mg parenteral doses of morphine. Adverse effects related to ketoprofen were relatively minor and infrequent. Ketoprofen was recently approved for use as an analgesic for treatment of mild to moderate pain in total daily doses up to 300 mg; the recommended initial dose is 25 to 50 mg every 6 to 8 hours as necessary.", "nan", "A randomized double-blind trial was performed to evaluate the efficacy of a new non-steroidal anti-inflammatory analgesic drug, ketorolac, in the treatment of cancer pain compared with the opioid pentazocine. A total of 40 patients with moderate to severe cancer pain were studied, 20 patients being treated with 10 mg ketorolac given orally every 6 h and 20 receiving 50 mg pentazocine given orally every 6 h for up to 7 days. A reduction in the severity of the pain was recorded in both treatment groups with no significant difference in efficacy being found between the two therapies, although withdrawals due to adverse reactions were significantly less in the ketorolac-treated group (p less than 0.005). It is concluded that ketorolac may be a useful and more acceptable alternative to opioids in the treatment of cancer pain.", "To compare the analgesic efficacy and safety of two single doses of ketorolac with diclofenac in acute cancer pain.\n Double-blind, randomized, clinical study.\n Hospital-based clinical research center.\n One hundred eighty patients suffering acute, moderate, or severe cancer pain.\n A single intramuscular injection of ketorolac 10 or 30 mg or diclofenac 75 mg.\n Pain intensity was assessed 30 minutes and 1, 2, 3, 4, 5, and 6 hours after injection or until rescue drug administration. In approximately 70% of patients all treatments provided prompt sustained pain relief throughout the 6-hour observation period. There were no statistically significant differences in any of the analyzed efficacy measures among the three groups.\n Intramuscular ketorolac 10 mg is adequate to relieve cancer pain, and is equivalent to ketorolac 30 mg and to diclofenac 75 mg.", "A prospective double-blind randomized trial was conducted on 184 cancer patients with moderate to severe chronic pain to evaluate the analgesic efficacy and tolerability of diclofenac alone (50 mg q.i.d.) or in combination with a weak opioid (codeine 40 mg q.i.d.), or with an anti-depressant (imipramine, 10 or 25 mg t.i.d.). All demographic and clinical characteristics including cancer type, presence of bone metastases, baseline pain severity, neuropathic and nociceptive pain, and depressive state, were well balanced between the three treatment groups. The main analysis of the study was on the VAS scores at visit 2 (day 4). The mean VAS values for both associations imipramine plus diclofenac and codeine plus diclofenac were similar to the association placebo plus diclofenac. Patients on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn mainly for inadequate efficacy, while patients on codeine plus diclofenac discontinued equally for inadequate efficacy or adverse events. In conclusion, in a short-term evaluation the addition of a tricyclic anti-depressant or a weak opioid to diclofenac did not provide further analgesia with respect to diclofenac administration alone.", "To compare the analgesic efficacy and toxicity of the nonsteroidal anti-inflammatory analgesic drug, ketorolac (Toradol, Recordati spa, Milan) 10 mg p.o. (t.i.d.) with diclofenac (Voltaren, Novartis Farma, Origglo, VA) 50 mg p.o. (t.i.d.) in cancer patients with moderate to severe chronic pain.\n The study was a multicenter randomized double-blind cross-over trial. Each treatment lasted 7 days, after which the patients crossed over to the other drug. Pain intensity was evaluated by the visual analogue scale (VAS) after the first dose and by the 5-point verbal rating scale (VRS) by the patient and by the physician following the 7-day treatment.\n A total of 138 advanced cancer patients were enrolled in the study. Overall 251 single-dose administrations (117 cross-over observations) and 257 multiple treatments (127 cross-over experiments) were assessable. After a single administration of ketorolac and diclofenac, no significant difference could be observed in analgesic activity, as indicated by the area under the pain-intensity time curve (AUC0-8), in the maximum efficacy, or the duration of efficacy of the two drugs. The Westlake confidence intervals of the AUC0-8 ratio (ketorolac: diclofenac) (1.07; 90% CI, 0.94-1.19), of the maximum efficacy ratio (1.03; 90% CI, 0.92-1.14), and the duration of efficacy ratio (1.05; 90% CI, 0.97-1.11) showed the bioequivalence of the two drugs. Satisfactory pain relief was reported for multiple 7-day treatments, with no significant differences between the two therapies: according to the physician's evaluation, in 93/128 (73%; 95% CI, 65-80%) ketorolac treatments and 91/129 (71%; 95% CI, 63-78%) diclofenac treatments; according to the patient's evaluation, in 83/128 cases (65%; 95% CI, 57-73%) after ketorolac and in 74/129 cases (57%; 95% CI, 49-66%) after diclofenac. Adverse symptoms were acceptable with both drugs. Interestingly, a pronounced sequence effect was found: gastric disturbances after ketorolac were observed mainly (10 out of 15 observed events) when the drug was given to patients pretreated with diclofenac.", "This randomized double-blind crossover study compares the narcotic methadone alone with methadone in combination with the peripherally acting, antiprostaglandin agent ibuprofen (Motrin, Upjohn) in 28 patients with moderate to severe cancer-related pain, who were already using a narcotic for pain relief. Results show that the addition of 600 mg of ibuprofen to either 2.5 or 5 mg of methadone significantly increased analgesia, without concomitantly increasing side effects or euphoria.", "It is uncertain whether there exists a nociceptive component in malignant nerve pain responsive to NSAIDs and opioids. 20 patients with malignant nerve pain were randomly assigned to treatment with naproxen 1500 mg versus slow-release morphine 60 mg daily during 1 week, followed by cross-over medication during the second week in a double-blind, double-dummy protocol. In the 16 evaluable patients, a significant (P < 0.05) reduction of 26% (S.E. +/- 7.9) in pain intensity was reached at day 7, compared to baseline pain. At day 7, significant pain relief of 32% (P < 0.05) was observed in the naproxen group, but not in the morphine group (21%, P = 0.14). Patients using morphine needed approximately twice as much paracetamol rescue than patients using naproxen. Additional pain relief could be observed in 4/9 patients with cross-over medication. These data support the concept of a nociceptive component in malignant nerve pain responding to NSAIDs and opioids, and favour the combination of both an anti-inflammatory drug and an opioid for symptomatic pain relief.", "In a randomized single-blind study carried out simultaneously in five Departments for Pain Therapy and Palliative Care, the analgesic efficacy and side effects of oral ketorolac (ketorolac tromethamine, Tora-Dol, CAS 74103-07-4) and diclofenac sodium were compared in a population of 100 advanced cancer patients suffering from somatic and/or visceral pain. The treatment was carried out in agreement with the first step of the WHO pharmacological strategy in cancer pain. The administered dosage was 10 mg every 6 h for ketorolac and 50 mg every 8 h for diclofenac sodium. The study showed the efficacy of both drugs in cancer pain. A greater number of keterolac patients could pass to the second WHO step later than diclofenac patients. As to the tolerability, both drugs turned out to be similar, except for \"sleepiness\", which was four times more frequent (p < 0.05) in the diclofenac group.", "The improved pain control provided by regular dosing of opioid analgesics in patients with severe cancer pain has been well established. However, the treatment of mild-to-moderate cancer pain is often limited to \"as needed\" dosing with fixed combinations of codeine or oxycodone plus a nonopioid analgesic, which do not allow optimal titration of the individual components. This randomized double-blind study was designed to evaluate the efficacy of controlled-release codeine (Codeine Contin) in patients with cancer pain, and to estimate its dose equivalence to a standard combination of acetaminophen plus codeine. Twenty-four patients with at least moderate cancer pain were randomized to Codeine Contin 100, 200, or 300 mg every 12 hr or acetaminophen plus codeine (600 mg/60 mg) every 6 hr. On days 1 and 4 of dosing, pain intensity and pain relief were assessed hourly for 12 hr. The sum of pain intensity differences (SPID) from baseline and the total pain relief (TOTPAR) scores demonstrated a dose-response relationship for Codeine Contin on days 1 and 4 that was statistically significant on day 1 and suggested greater analgesic efficacy on day 4, compared with day 1. Codeine Contin 150 mg every 12 hr was estimated to be equianalgesic to acetaminophen plus codeine (600 mg/60 mg) given every 6 hr. Because a similar equivalence was also demonstrated from analysis of adverse event data, it is concluded that Codeine Contin 150 mg produces analgesia and a side-effect profile similar to a 40% lower dose of codeine provided by the combination.(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare the effectiveness of intravenous patient-controlled (i.v.-PCA) ketorolac to i.v.-PCA morphine in the treatment of postoperative pain in cancer patients.\n In a double-blind, prospective, randomized trial, patients received either morphine in 1 mg/ml concentration or ketorolac 5 mg/ml for postoperative pain control. On arrival to the postanesthesia care unit (PACU), the patients received 2 ml of medication every 5 min, until satisfactory analgesia was achieved. If pain persisted after 20 ml of study drug had been administered, 0.1 mg/kg morphine was given i.m. On discharge from the PACU, the patients were placed on an i.v.-PCA pump. All patients received a basal infusion of 1 ml/h with a 1-ml on-demand bolus and a lockout interval of 10 min. Patients were offered 0.1 mg/kg morphine IM every 6 h, which they could refuse.\n University Cancer Center.\n Seventy patients scheduled for abdominal or truncal cancer operations.\n Visual analog pain scores (VAPS) and Visual analog sedation scores (VASS) were used to measure the quality of pain control achieved either with ketorolac or morphine. The incidence of side effects was documented.\n The VAPS were comparable between the groups. Patients in the ketorolac group requested more supplemental i.m. morphine. However, the total morphine dose and incidence of side effects was significantly higher in patients receiving i.v.-PCA morphine.\n These results indicate that ketorolac supplemented with small doses of morphine is associated with a lower incidence of nausea, vomiting, and pruritus compared to morphine alone. This combination should be considered where immunosuppression from operation and administration of morphine is undesirable.", "Twenty-six patients with painful, bony metastases were recruited into a randomized, double-blind, single dose, two-treatment, three-part crossover study of choline magnesium trisalicylate (CMT) and placebo. Assessments were made prior to and at one, two, three and four hours after dosing. Bone pain caused by metastatic cancer was significantly relieved one hour after the administration of 1500 mg CMT (p = 0.04). At all four time points the pain was less than baseline with CMT and at three time points greater than baseline with placebo but these results did not reach statistical significance. The summed pain intensity difference for patients was greater with CMT than with placebo, but this also did not reach significance. The incidence of volunteered side-effects was similar for both treatments. The results suggest that a nonacetylating, nonsteroidal anti-inflammatory drug may have a role complementary to that of an opioid in the management of metastatic bone pain.", "nan", "The effectiveness of diclofenac 50 mg t.i.d. as additive treatment to parenteral patient-controlled administration therapy (PCAT) with morphine in cancer pain has been investigated in a double-blind study. In the fifteen patients who completed the study, morphine i.v. was titrated to optimal pain relief over 5 days. The mean total morphine consumption was significantly reduced during diclofenac administration (82.8 mg morphine per day) compared to placebo (95.0 mg morphine per day). The reduction in mean morphine consumption during active treatment with diclofenac was independent of the initial dose of self-titrated morphine. Pain, self-assessed according to VAS, tended to be lower during the diclofenac period, although the difference did not reach statistical significance. No adverse events were recorded among the 15 patients who completed the study. The present findings show that a non-steroidal anti-inflammatory agent, such as diclofenac, has a morphine-sparing effect in morphine-treated patients with cancer pain.", "In a single-blind random study, simultaneously carried out by five Pain Therapy and Palliative Care Centres, the analgesic power and side-effects of sodium naproxen (CAS 26159-34-2) and sodium diclofenac (CAS 15307-86-5) by mouth were compared in a group of 100 advanced cancer patients. The patients complained of somatic and/or visceral pain and were treated with non-steroid anti-inflammatories as required. The dose administered amounted to 550 mg every 12 h for sodium naproxen and to 100 mg every 12 h for sodium diclofenac. The study stressed the similar analgesic effect of the two drugs--pain intensity and duration decreased by half in the first week of treatment--and a comparatively low morbidity rate.", "The efficacy and tolerability of acetylsalicylic acid, paracetamol, diclofenac, ibuprofen, indomethacin, pirprofen, sulindac, naproxen and suprofen were compared in the treatment of cancer pain. In a double-blind, within-patient randomized study, each drug was given for 1 week to eight patients and for another week to a further eight patients. A total of 65 patients were effectively treated; only 48 completed week 1 and 41 completed week 2. Naproxen, diclofenac and indomethacin were highly effective in pain relief (tested by means of a 100 mm visual analogue scale) and were relatively well tolerated. It is concluded that these non-steroidal anti-inflammatory drugs can be considered as first choice in the treatment of cancer pain.", "The analgesic effects of single oral doses of ketoprofen 100 and 300 mg, the combination of aspirin 650 mg plus codeine 60 mg, and placebo were compared under double-blind conditions in 160 hospitalized patients with cancer pain. At baseline and at 30 minutes and hourly for 6 hours after treatment, patients evaluated their pain intensity and pain relief. The 100 mg ketoprofen dose was significantly (P less than 0.05) superior to placebo for all 14 derived efficacy parameters; the 300 mg dose was significantly superior to placebo in all assessments except derived onset of relief. Aspirin plus codeine was significantly (P less than 0.05) superior to placebo for nine of the 14 assessments. No statistically significant differences were observed among active treatments for any of the 14 derived parameters. The number of patients with a \"good\" response was greatest in the ketoprofen 100 mg group (55%); the numbers of good responders in the aspirin plus codeine (37.5%) and the ketoprofen 300 mg (30%) groups were comparable. The three active treatment groups were not significantly different from each other for patient response. The numbers of patients requiring rescue analgesic were significantly (P less than 0.05) lower for both ketoprofen groups, but not for the aspirin plus codeine group, as compared with the placebo group. Twenty-three percent of the 160 patients reported adverse experiences, but there were no significant differences between the treatment groups in the number or type of experience. These results show that ketoprofen is as effective and well tolerated as aspirin plus codeine in relieving cancer pain.", "The efficacy of diflunisal in cancer pain was evaluated and compared with dipyrone. Diflunisal was given at the dosage of 500 mg perorally twice a day, and dipyrone was given at the dosage of 500 mg perorally three times a day. Duration of each treatment was 7 days; after a 12-hour wash-out period, patients were given the other drug for another 7 days. A total of 50 patients were enrolled in the study. Pain intensity was assessed by 10-point visual analog scale (VAS). Patients who had a VAS score higher than 5 were included. A total of 47 patients were evaluable. Initial VAS score was a mean of 8.57+/-1.33. Diflunisal reduced the pain score by a mean of 4.65+/-3.10, whereas dipyrone reduced the pain score by a mean of 3.25 < or = 2.85 (p < 0.001). Patients were also analyzed in three subgroups according to the presence of nonmetastatic, metastatic, and bone metastatic diseases. In each of these subgroups, diflunisal reduced the pain score more than dipyrone; however, the difference was statistically significant only in patients who had bone metastasis. Adverse reactions were rare and acceptable with both drugs. Diflusinal is superior to dipyrone at this dosage and schedule in the treatment of moderate to severe cancer pain.", "nan", "The analgesic efficacy of ketorolac tromethamine was compared to placebo in 126 patients suffering moderate or severe chronic pain due to cancer in a double-blind parallel randomized study. Ketorolac was administered intramuscularly in doses of 10, 30 or 90 mg. Pain intensity and pain relief were assessed for 6 hours by scoring standard verbal scales and an overall assessment of the medication was given by the patients and the observer on completion of the study. Each dose of ketorolac was statistically superior to placebo for the sum of pain intensity difference (SPID) but no difference was seen between the three ketorolac regimens. When the ketorolac groups are combined, there was a significantly better pain relief as compared to placebo. The global evaluation scores were also statistically superior in the ketorolac groups combined than in the placebo group. A total of 15 patients reported minor adverse events, 10 being after ketorolac doses. This study shows that single intramuscular doses of ketorolac of 10 mg and above are effective in the relief of cancer pain, and are associated with a low incidence of side-effects.", "Seventy-five patients with moderate to severe cancer pain were randomly assigned in a double-blind fashion to receive first-dose ketorolac tromethamine 10 mg orally, acetaminophen 600 mg plus codeine 60 mg orally, or placebo, followed by subsequent doses of ketorolac or acetaminophen plus codeine four times daily for 7 days. Patient characteristics were similar among the treatment groups. The first-dose observation documented that both ketorolac and acetaminophen plus codeine produced an equivalent reduction in cancer pain and were superior to placebo as measured by pain intensity differences and pain relief. Multidose comparison documented a small but statistically significant advantage in mean daily pain relief favoring acetaminophen plus codeine, although there were no differences in mean daily ratings of overall effects for either study medication. Adverse symptoms were acceptable with both ketorolac and acetaminophen plus codeine. We conclude that ketorolac has significant analgesic activity in patients with cancer pain, although its precise role in the treatment regimen of these patients remains undefined.", "In a multicentric, interindividual, double-blind study, the analgesic action, duration of effect, tolerability and side effects of the new combination preparation, Combaren (diclofenac-Na 50 mg+codeine phosphate 50 mg), were compared with those of diclofenac-Na 50 mg (Voltaren 50) in 184 patients with severe tumor-related pain. The results show that Combaren is a highly effective preparation for the treatment of severe tumor pain. The combination of diclofenac-Na with codeine phosphate leads to a clear, statistically significant, augmentation of the effectiveness of additionally used analgesics on pain severity, and the general effectiveness of the combination is more positively assessed that that of monotherapy with diclofenac (also effective). In the staged approach to the treatment of malignancy-related pain in which the aim is to provide continuous, preventive analgesia rather than ad hoc treatment of newly developing or worsening pain, this combination preparation will presumably find a permanent place in stage I/II of the generally accepted staged pain-treatment scheme.", "In a clinical double-blind study, the analgesic efficacy and the side-effects of nimesulide (Aulin, CAS 51803-78-2) and naproxen administered to 68 patients affected by advanced cancer pain were compared. Patients were treated with non-steroidal anti-inflammatory drugs according to the first step of the pharmacological analgesic scale of the WHO. The dose administered was 200 mg b.i.d. (every 12 h) for nimesulide and 500 mg b.i.d. (every 12 h) for naproxen. From this study the analgesic effect and the tolerability of the two drugs appeared to be similar. Both drugs resulted to be effective with a low incidence of adverse events that may be related to their use.", "This double-blind, placebo controlled study compared the analgesic efficacy of piroxicam with acetylsalicylic acid (ASA) in patients having continuous pain with advanced head and neck cancers. They were randomly divided into two groups of 25 patients each; 36 of these 50 patients completed the study. After four days of treatment, there was a significant reduction in a modified numerical rating scale (NRS) of pain in the piroxicam group as well as in the ASA group. There was a concomitant increase in the hours of sleep in the piroxicam group and in the ASA group. The decrease in NRS and the increase in sleeping hours was not statistically significantly different between the two groups. Patients receiving piroxicam had a low incidence of upper gastrointestinal side-effects compared with those receiving ASA. The results of this study suggest that piroxicam can be used as first line treatment in place of ASA in patients with head and neck cancers suffering from moderate to severe pain. The advantages are less frequent dosing, better patient compliance and few side-effects.", "The analgesic efficacy and toxicity of oral diclofenac sodium 50 mg (q.i.d.) vs. nefopam 60 mg (q.i.d.) and a combination of 640 mg ASA and 40 mg codeine (q.i.d.) in cancer patients with moderate to severe chronic pain has been evaluated in a randomized double-blind study. Planned duration of treatment was 10 days. Pain intensity was evaluated by a visual analog scale. The length of patient participation in the trial, the patient's final global evaluation and the incidence of side effects were also evaluated. Ninety-nine patients were enrolled in the study. All treatments produced a statistically significant pain relief (P less than 0.01) without differences among groups but only 26 of 99 patients (26.3%) completed the planned treatment period. Mean time in the study was 4.65 days. Inefficacy and side effects were the main reasons for premature treatment interruption. Patients treated with nefopam had a significantly shorter period in the study than patients treated with the other 2 treatments. Adverse effects were slightly more frequent with the nefopam and ASA + codeine regimens. The 3 therapeutic regimens appear to be similar as to analgesic efficacy, but diclofenac presents the advantage of a slightly better safety profile than nefopam and the ASA + codeine combination.", "A scheduled regimen of oral narcotic analgesics was compared with a regimen of oral narcotic analgesics plus ibuprofen for analgesic efficacy in patients with cancer. Ten patients with metastatic cancer were randomly assigned to receive either ibuprofen 400 mg or a look-alike placebo four times daily in addition to each patient's existing regimen of scheduled oral narcotics. A two-period changeover study design was used. The 24-hour narcotic intake equated to injectable morphine was computed for each patient at baseline and during the nine study days. A visual analogue scale was used to evaluate pain relief, nausea, mood depression, daytime drowsiness and nighttime sleeplessness. The analgesic efficacy of the narcotic-ibuprofen combination was significantly greater than the analgesic efficacy of the narcotic-placebo combination. Eight patients demonstrated a positive treatment effect with added ibuprofen; the overall improvement in analgesia averaged 39.1% in these patients. There was no significant increase from baseline in the incidence of nausea, mood depression, daytime drowsiness or nighttime sleeplessness. At the doses used in this study, a treatment regimen of oral narcotic analgesics plus ibuprofen was more effective than oral narcotics alone in relieving pain associated with cancer." ]

[ "18021264", "20467641", "20467604" ]

[ "Asepsis during periodontal surgery involving oral implants and the usefulness of peri-operative antibiotics: a prospective, randomized, controlled clinical trial.", "Efficacy of prophylactic antibiotics for dental implants: a multicentre placebo-controlled randomised clinical trial.", "A multicentre placebo-controlled randomised clinical trial of antibiotic prophylaxis for placement of single dental implants." ]

[ "This randomized clinical trial compares the usefulness of pre- and post-operative antibiotics while strict asepsis was followed during periodontal surgery.\n Two groups of 40 consecutive patients each with fully or partially edentulous jaws were enrolled. Antibiotics group (GrAB(+)): 23 men, mean age 60, 128 implants, received oral amoxicillin 1 g, 1 h pre-operatively and 2 g for 2 days post-operatively. Non-antibiotics group (GrAB(-)): 20 men, mean age 57, 119 implants, received no antibiotics. Bacterial samples were taken from the peri-oral skin before and at the end of surgery. In 12 patients in each group, samples were also taken from the nares. A VAS questionnaire evaluated symptoms of infection/inflammation by both the patient and the periodontologist at suture removal.\n There were no significant differences between both groups, neither for the clinical parameters nor for the microbiota. Staphylococcus aureus was detected in the nares of one patient only. The patients' subjective perception of post-operative discomfort was significantly smaller in the group receiving antibiotics. Three patients lost one or two implants.\n Antibiotics do not provide significant advantages concerning post-operative infections in case of proper asepsis. It also does not reduce peri-oral microbial contamination. It does on the other hand reduce post-operative discomfort.", "To evaluate the efficacy of prophylactic antibiotics for dental implant placement.\n Twelve Italian private practices agreed to participate in this trial, each centre providing 30 patients. One hour prior to implant placement, patients were randomised, for consumption orally of 2 g amoxicillin or identical placebo tablets. Patients needing bone augmentation procedures were not included. Outcome measures were prosthesis and implant failures, adverse events and post-operative biological complications. Patients were seen 1 week, 2 weeks and 4 months post-operatively.\n One centre did not deliver any data and 14 patients had to be excluded from the trial for various reasons. One hundred and fifty-eight patients were evaluated in each group and none dropped out at 4 months. Two prostheses and two implants failed in the antibiotics group, compared with four prostheses and nine implants in the placebo group. There were no statistically significant differences for prosthesis failures, implant losses, complications and side effects.\n No statistically significant differences were observed. However, four times more patients in the placebo group experienced implant failures than in the antibiotic group, and this requires further investigation.", "To compare the efficacy and safety of 2 g amoxicillin orally with identical placebo tablets 1 hour before implant placement when placing single implants in bone types II and III.\n 12 private dental clinics in Spain agreed to participate in this trial. A total of 105 patients were recruited. Patients were randomised for consumption orally of 2g amoxicillin or identical placebo tablets. Only patients needing single implants were included. Outcome measures were post-operative infections, adverse events and implant failures. Characteristics of the saprophytic flora were also studied in all patients. Patients were seen 3 days, 10 days, 1 month and 3 months postoperatively. Results: A total of 105 patients (n = 52 in the amoxicillin group and n = 53 in the placebo group) were evaluated and none were excluded from the study at 3 months. Six post-operative infections occurred and two implants were lost in each group. There were no statistically significant differences for postoperative infection, adverse events, implant failures and the characteristics of saprophytic flora between groups. The use of amoxicillin did not either alter or modify the characteristics of the saprophytic flora nor provoke remarkable side effects.\n Antibiotic prophylaxis may not be needed when placing single implants in patients with bone types II and III." ]

[ "8513962" ]

[ "A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis." ]

[ "To evaluate the efficacy of goserelin versus a low-dose cyclic oral contraceptive (OC) in improving pelvic pain in women with endometriosis and to compare recurrence of symptoms during follow-up.\n Open-label, randomized trial.\n University hospital endometriosis center.\n Fifty-seven women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis.\n Six-month treatment with goserelin depot (n = 29) or a low-dose cyclic OC (n = 28) followed by 6-month follow-up.\n Variation in severity of symptoms during treatment and at the end of follow-up as shown by a linear analog scale and a verbal rating scale.\n At 6 months of treatment, a significant reduction in deep dyspareunia was observed in both groups, with goserelin superior to the OC at linear analog scale assessment. Nonmenstrual pain was diminished on both scales without differences between treatments. Women taking the OC experienced a significant reduction in dysmenorrhea. At the end of follow-up, symptoms reappeared without differences in severity between the groups.\n Low-dose cyclic OCs may be a valuable alternative for the treatment of dysmenorrhea and nonmenstrual pain associated with endometriosis. Symptoms recurred in most subjects 6 months after drug withdrawal." ]

[ "1487623" ]

[ "Positive and negative symptoms, depression and social disability in chronic schizophrenia: a comparative trial of bromperidol and fluphenazine decanoates." ]

[ "A 1 year double-blind trial of bromperidol decanoate and fluphenazine decanoate was conducted in the maintenance treatment of 47 outpatients with schizophrenia. Six patients relapsed on bromperidol decanoate and none on fluphenazine decanoate, a difference which is statistically significant. No significant differences in positive and negative symptoms, nor depression measures were found between treatment groups when comparisons were made for change in score from entry to last visit. However, patients on fluphenazine decanoate achieved significantly better changes on social disability (Morningside scale) compared to those on bromperidol decanoate. The incidence of extrapyramidal side-effects was similar in both groups, and no statistically significant differences emerged in body weight change between treatments." ]

[ "8463913" ]

[ "Randomized study of high-frequency oscillatory ventilation in infants with severe respiratory distress syndrome. HiFO Study Group." ]

[ "We conducted a multicenter, prospective, noncrossover, randomized study to determine whether high-frequency oscillatory ventilation (HFOV) would decrease the development or progression of air leak syndrome in infants with severe respiratory distress syndrome. Air leak syndrome was defined as pulmonary interstitial emphysema or gross air leak such as pneumothorax. Infants were eligible for study entry if they were less than 48 hours of age and had severe respiratory distress syndrome, defined by peak inspiratory pressure or the presence of air leak syndrome. Infants who weighed > or = 0.5 kg at birth were randomly assigned to receive either conventional ventilation (CV) or HFOV. HFOV was provided by a ventilator that operated at 15 Hz, with a 1:2 inspiratory/expiratory ratio and no background tidal breaths. Severity of pulmonary interstitial emphysema was scored independently by two neonatologists unaware of the infants' ventilatory group. Gross air leak severity was scored according to the number of chest tubes required and duration of air leak. Eighty-six infants received HFOV; 90 received CV. During the first 24 hours of the study, patients in the HFOV group received significantly higher mean airway pressure and lower inspired oxygen concentration, had significantly lower arterial carbon dioxide tension, and had a higher ratio of arterial to alveolar oxygen tension. When the HFOV and CV groups were compared with control for birth weight strata, study site, and inborn versus outborn status, HFOV significantly reduced the development of air leak syndrome in those patients who entered the study without the syndrome. We conclude that HFOV, when the strategy employed in this study is used, provides effective ventilation, improves oxygenation, and significantly reduces the development of air leak syndrome in infants with severe respiratory distress syndrome." ]

[ "17082463", "11677003", "21172842", "20808854", "10994885" ]

[ "Randomized, double-blind, placebo-controlled trial of phenylbutyrate in spinal muscular atrophy.", "A placebo-controlled trial of gabapentin in spinal muscular atrophy.", "Randomized, double-blind, placebo-controlled trial of hydroxyurea in spinal muscular atrophy.", "SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy.", "A study of thyrotropin-releasing hormone for the treatment of spinal muscular atrophy: a preliminary report." ]

[ "To assess the efficacy of phenylbutyrate (PB) in patients with spinal muscular atrophy in a randomized, double-blind, placebo-controlled trial involving 10 Italian centers.\n One hundred seven children were assigned to receive PB (500 mg/kg/day) or matching placebo on an intermittent regimen (7 days on/7 days off) for 13 weeks. The Hammersmith functional motor scale (primary outcome measure), myometry, and forced vital capacity were assessed at baseline and at weeks 5 and 13.\n Between January and September 2004, 107 patients aged 30 to 154 months were enrolled. PB was well tolerated, with only one child withdrawing because of adverse events. Mean improvement in functional score was 0.60 in the PB arm and 0.73 in placebo arm (p = 0.70). Changes in the secondary endpoints were also similar in the two study arms.\n Phenylbutyrate was not effective at the regimen, schedule, and duration used in this study.", "To evaluate the efficacy of gabapentin in increasing muscle strength of patients with spinal muscular atrophy (SMA).\n Preclinical data in experimental models of motor neuron disease suggest a neuroprotective effect of gabapentin.\n Gabapentin (1200 mg), or placebo, was administered three times daily in a randomized, double-blind trial for 12 months. The primary outcome measure was the average percent change from baseline, based on the measurement of strength in four muscles (elbow flexion and hand grip bilaterally) for each patient. Drug efficacy was examined by comparing the percent change in strength for patients on drug vs. placebo. Secondary efficacy variables included: forced vital capacity (FVC), SMA functional rating scale (SMAFRS), and mini-Sickness Impact Profile (SIP).\n Eighty-four patients, with type II or III SMA, were enrolled at eight sites across the United States. There were no differences in baseline features. There was no difference between the placebo and drug groups in any outcome measure.\n This study demonstrates the feasibility of this trial design and provides data for the design of future clinical trials in SMA.", "The purpose of this study was to evaluate the safety and efficacy of hydroxyurea (HU) in spinal muscular atrophy (SMA) in a randomized, double-blind, placebo-controlled trial.\n Twenty-eight patients with type 2 SMA and 29 patients with type 3 SMA were randomly assigned (2:1) to receive HU or matching placebo for 18 months. HU was initiated at 10 mg/kg/day with an 8-week titration to 20 mg/kg/day. Subjects were assessed at baseline (T0) and monthly for the first 2 months (T1-T2) and then every 2 months throughout treatment (T3-T10) and posttreatment periods (T11-T13). The primary outcome measures were the Gross Motor Function Measure (GMFM), Manual Muscle Test (MMT), and serum full-length survivor motor neuron (flSMN) mRNA. The secondary outcome measures were Modified Hammersmith Functional Motor Scale and forced vital capacity (FVC).\n Fifty-five patients completed this trial, which lasted from March 2007 to June 2009. Except for neutropenia, we found no differences in adverse events between the 2 groups. Compared with the placebo group, the HU group had -1.88 for GMFM (p = 0.11), -0.55 for MMT (p = 0.49), and 2.17 for flSMN mRNA (p = 0.13). Similarly, we found no difference in mean improvement of the secondary endpoints. Both groups had a trend toward a decline in FVC with little change in strength and motor function.\n Under the current regimen and schedule, HU brought about no improvement in patients with type 2 and 3 SMA, and its main side effect was neutropenia. Classification of evidence: This trial provides Class I evidence that HU 20 mg/kg/day does not effectively treat SMA.", "Valproic acid (VPA) has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA) in vitro and in vivo.\n Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory group of \"sitters\" (cohort 1) and an ambulatory group of \"walkers\" (cohort 2). Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of age. Sixty-one subjects were randomized 1:1 to placebo or treatment for the first six months; all received active treatment the subsequent six months. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS) score following six months of treatment. Secondary outcomes included safety and adverse event data, and change in MHFMS score for twelve versus six months of active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar CMAP amplitudes, myometry and PFT measures.\n At 6 months, there was no difference in change from the baseline MHFMS score between treatment and placebo groups (difference = 0.643, 95% CI = -1.22-2.51). Adverse events occurred in >80% of subjects and were more common in the treatment group. Excessive weight gain was the most frequent drug-related adverse event, and increased fat mass was negatively related to change in MHFMS values (p = 0.0409). Post-hoc analysis found that children ages two to three years that received 12 months treatment, when adjusted for baseline weight, had significantly improved MHFMS scores (p = 0.03) compared to those who received placebo the first six months. A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores (p = 0.007).\n This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA. Weight gain, age and treatment duration were significant confounding variables that should be considered in the design of future trials.\n Clinicaltrials.gov NCT00227266.", "To determine whether thyrotropin-releasing hormone (TRH) can increase muscle strength in children with spinal muscular atrophy types 2 and 3.\n A randomized, double-blinded, controlled, 5-wk drug trial of six subjects and three controls. Subjects and controls ranged from 4 to 8 yr of age and were randomly assigned to treatment and placebo groups in a ratio of 2:1. TRH (protirelin) or placebo was delivered intravenously through percutaneous intravenous catheters at a dose of 0.1 mg/kg (in 50 ml of normal saline) for a total of 29 days. Patients were evaluated using electromyography and handheld dynamometry of the deltoids, biceps, triceps, wrist extensors, hip flexors, quadriceps, hamstrings, and grip strength before and immediately after 5 wk of treatment. A unidirectional t test was used to compare mean values.\n Dynamometry improved significantly only for the six treated subjects (P < 0.02). Peroneal nerve conduction velocities were significantly faster in the treatment group (paired t test, P = 0.036). The parents of the treated children also provided anecdotal evidence of improvements in function. Improvements lasted 6-12 mo.\n TRH may be a useful treatment for spinal muscular atrophy. A larger, crossover design group comparison study is warranted." ]

[ "12786704", "15996411", "11991271", "2654207", "3312331", "10469077", "20483861" ]

[ "Comparative trial between sodium tetradecyl sulfate and glycerin in the treatment of telangiectatic leg veins.", "Double-blind prospective comparative trial between foamed and liquid polidocanol and sodium tetradecyl sulfate in the treatment of varicose and telangiectatic leg veins.", "Treatment of varicose and telangiectatic leg veins: double-blind prospective comparative trial between aethoxyskerol and sotradecol.", "Treatment of essential telangiectasia: effects of increasing concentrations of polidocanol.", "Treatment of telangiectasia: comparison of sclerosing agents.", "Sclerotherapy for leg telangiectasia--a blinded comparative trial of polidocanol and hypertonic saline.", "Sclerotherapy of telangiectases and reticular veins: a double-blind, randomized, comparative clinical trial of polidocanol, sodium tetradecyl sulphate and isotonic saline (EASI study)." ]

[ "Thirteen patients were treated with either sodium tetradecyl sulfate (STS) or glycerin to compare the efficacy and adverse sequelae of each agent.\n To determine the relative safety and efficacy of two sclerosant solutions.\n Each patient's leg veins that were from 0.2 to 0.4 mm in diameter and that did not have incompetence from the saphenofemoral junction and whose feeding reticular veins had been already treated in a prior sclerotherapy session were randomly treated with either 0.25% STS or 72% glycerin solution. Patients were evaluated from 2 to 6 months postsclerotherapy for overall clinical improvement and incidence of adverse sequelae.\n Glycerin was comparable to STS in discomfort of injection but demonstrated a significant decrease in bruising, swelling, and postprocedural hyperpigmentation. Glycerin also demonstrated a better, more rapid clearance of treated telangiectasias.\n Seventy-two percent glycerin is a safe and effective sclerosant with fewer side effects and more rapid clearance of telangiectatic leg veins than STS.", "Twenty subjects were treated with either polidocanol (POL) or sodium tetradecyl sulfate (STS) to compare the efficacy and adverse sequelae of each agent.\n To determine the safety and efficacy of two widely used sclerosing agents.\n After the exclusion of saphenofemoral junction incompetency, each subject's leg veins were categorized by size (< 1, 1-3, and 3-6 mm in diameter). Each leg was then randomized to be treated with 0.5%, 1%, or 1% foam of POL or 0.25%, 0.5%, or 0.5% foam of STS according to vein size. An independent panel of four physicians, blinded to treatment, performed randomized photographic evaluations obtained pretreatment and 12 weeks post-treatment. Subject satisfaction index and overall clinical improvement assessment were also obtained.\n An average 83% improvement was noted for all vein sizes in all subjects with both POL and STS after a single treatment. Subjects were satisfied with treatment, regardless of the sclerosing agent used or the vein size treated. There was no statistically significant difference in adverse effects between each group.\n Both POL and STS are safe and effective sclerosing agents in the treatment of varicose and telangiectatic leg veins. Both are very tolerable and demonstrate similar post-treatment sequelae.", "One hundred twenty-nine patients were treated with either polidocanol (POL) or sodium tetradecyl sulfate (STS) to compare the efficacy and adverse sequelae of each agent.\n To determine the safety and efficacy of two sclerosing solutions.\n Each patient's leg veins that did not have incompetence from the saphenofemoral junction (SFJ) were divided into three categories by size (<1 mm, 1-3 mm, 3-6 mm). Each leg was randomly treated with either 0.25%, 0.5%, or 1.5% of STS or 0.5%, 1.0%, or 3% of POL respective of size. An independent, three-panel, blindly randomized photographic examination was obtained pretreatment and at 4 and 16 weeks. Patient satisfaction index and overall clinical improvement assessment were also obtained.\n All patients had an average of 70% improvement and were 70-72% satisfied in all vein categories treated with either solution. There was no significant difference in adverse effects between each group except for a decrease in ulcerations and swelling in the POL group.\n Both STS and POL are safe and effective sclerosing solutions for varicose and telangiectatic leg veins.", "A double-blind, double-paired comparison study was performed to evaluate the effects of increasing concentrations of polidocanol in the sclerotherapy of essential telangiectasias of the legs. Polidocanol 0.25%, 0.50%, 0.75%, and 1.0% were compared with regard to clinical effectiveness, safety, and patient acceptance. All dosages were well tolerated by the patients. There were no allergic reactions to polidocanol and no cases of superficial ulceration nor necrosis. Among those whose veins cleared, there was little difference in time to clearing for the four concentrations, which averaged three to four treatment sessions. No statistically significant differences existed among the four dosages with respect to level of improvement, itching, or neovascularization. Polidocanol 0.75% and 1.0%, however, caused more side effects noted by patients and induced more hyperpigmentation than did the lower concentrations. Polidocanol 0.25% yielded the lowest percentage of patients whose veins cleared. The 0.50% solution was the most effective concentration for total overall clearing of the types of vessels treated in this study. From this information it appears that 0.50% polidocanol may be the sclerosing agent of choice.", "A double-blind, double-paired comparison, placebo-controlled study was undertaken to determine the optimal agent for sclerotherapy of spider telangiectasias of the lower extremities. Sodium tetradecyl sulfate 0.5%, polidocanol 0.25%, heparsal, and normal saline control were evaluated in terms of clinical effectiveness and patient acceptance. Although all of the agents, except for the control, were effective, polidocanol was found to have the fewest adverse reactions and afforded the greatest patient comfort.", "Hypertonic saline (HS) and polidocanol (POL) have been in use around the world for sclerotherapy of telangiectasia for many years. However, despite numerous articles in the literature extolling the virtues of their individual use, few studies scientifically compare their relative efficacies.\n To compare, in a statistically significant number of female patients, the relative efficacy of hypertonic saline and polidocanol as sclerosants of leg telangiectasia and reticular feeding veins, using each patient as her own control.\n Eighty-one women with roughly matching leg telangiecasia were treated with sclerotherapy. One leg was injected with 20% saline/2% lignocaine, the other with 1% polidocanol, with the patients blinded as to the sclerosant used for each leg. Assessment of percent reduction of vessels, and the complications of matting and hemosiderin staining was conducted at 2 months by 3 methods: the patient's satisfaction, the treating physician's evaluation, and blinded assessment of before and after photographs.\n There was no statistically significant difference between HS and POL treated legs when assessed clinically or photographically. However, POL caused more staining and matting, and despite patients finding HS more painful at injection, patient satisfaction at follow-up was higher with the HS treated leg.\n 20% HS and 1% POL have equal efficacy in sclerosing leg telangiectasia and reticular feeding veins. POL causes more adverse sequelae, although these may be related to the solution concentration.", "To assess the efficacy and safety of polidocanol (POL) in comparison to sodium tetradecyl sulphate (STS) and isotonic saline (placebo) for sclerotherapy of telangiectases or reticular veins by means of standardized digital imaging system, independent medical observers and detailed monitoring.\n Of 316 randomized patients, 160 with telangiectases were randomly assigned to 0.5% POL, 1% STS or placebo, and 156 with reticular veins received 1% POL, 1% STS or placebo. Veins selected for injection were clearly visible telangiectases or reticular veins in a predefined treatment area (10x10 cm). Exact retrieval of the location was guaranteed by a newly established digital imaging system. Images were taken before first injection and 12 and 26 weeks after the last of three possible injection visits, and evaluated by the investigator and two blinded independent observers. The detailed safety monitoring included ultrasound screening for 'silent' deep vein thrombosis, electrocardiograms and clinical laboratory tests.\n POL demonstrated a statistically significant superiority versus placebo (P < 0.0001) for the primary criterion 'improvement of veins'. Significantly more patients were satisfied with POL at 12 or 26 weeks (84%, 88%) compared to STS (64%, 63%; P < 0.0001) and placebo (14%, 11%; P < 0.0001). POL was safe and well tolerated apart from expected local symptoms at the injection site.\n Sclerotherapy of telangiectases and reticular veins with detergent-like sclerosants such as polidocanol (POL) or sodium tetradecyl sulphate (STS) is a well-established technique. However, evidence from clinical trials comparing these substances with a non-active solution is sparse and does not live up to expectations of modern clinical trial concepts necessary for authorisation purposes. The presented multicentre EASI study fulfils these requirements and clearly demonstrates that Sclerotherapy of C1 veins with POL is highly effective and deserves the adjunct 'gold standard'." ]

[ "18849193", "781439", "12391494", "17942873", "10593672" ]

[ "Prednisolone and valaciclovir in Bell's palsy: a randomised, double-blind, placebo-controlled, multicentre trial.", "The use of steroids in Bell's palsy: a prospective controlled study.", "Influence of early high-dose steroid treatment on Bell's palsy evolution.", "Early treatment with prednisolone or acyclovir in Bell's palsy.", "Corticosteroid treatment of childhood Bell's palsy." ]

[ "Previous trials of corticosteroid or antiviral treatments for Bell's palsy have been underpowered or have had insufficient follow-up. The aim of this study was to compare the short-term and long-term effects of prednisolone and valaciclovir in the recovery of the affected facial nerve in a large number of patients.\n In this randomised, double-blind, placebo-controlled, multicentre trial, patients aged 18 to 75 years who sought care directly or were referred from emergency departments or general practitioners within 72 h of onset of acute, unilateral, peripheral facial palsy, between May, 2001, and September, 2006, were assessed. Patients were randomly assigned in permuted blocks of eight to receive placebo plus placebo; 60 mg prednisolone per day for 5 days then reduced by 10 mg per day (for a total treatment time of 10 days) plus placebo; 1000 mg valaciclovir three times per day for 7 days plus placebo; or prednisolone (10 days) plus valaciclovir (7 days). Follow-up was for 12 months. The primary outcome event was time to complete recovery of facial function, as assessed with a regional Sunnybrook scale score of 100 points. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00510263.\n Of 839 patients who were randomly assigned, 829 were included in the modified intention-to-treat analysis: 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valaciclovir plus placebo, and 206 prednisolone plus valaciclovir. Time to recovery was significantly shorter in the 416 patients who received prednisolone compared with the 413 patients who did not (hazard ratio 1.40, 95% CI 1.18 to 1.64; p<0.0001). There was no difference in time to recovery between the 413 patients treated with valaciclovir and the 416 patients who did not receive valaciclovir (1.01, 0.85 to 1.19; p=0.90). The number of patients with adverse events was similar in all treatment arms.\n Prednisolone shortened the time to complete recovery in patients with Bell's palsy, whereas valaciclovir did not affect facial recovery.", "A prospective, controlled, double-blind study was designed to evaluate the effect of steroid treatment on the natural history of Bell's palsy. Fifty-one patients were included in the study between 1972 and 1974. The patients were evaluated and started on treatment within two days of onset of Bell's palsy and followed for six months. Treatment was given in randomized double-blind fashion and consisted of either vitamins or a total of 410 mg of prednisone plus vitamins in descending doses over 10 days. The recovery of facial motor function was determined by three physicians who had no knowledge of the treatment received by the patients. They examined photographs of the patients taken six months after onset of paralysis in eight positions of facial function and categorized them as to complete fair, or poor recovery of facial function. These results of this evaluation were submitted to the biostatistician who broke the treatment code. The results of this study demonstrate no statistically significant beneficial effect of steroid therapy upon recovery from Bell's palsy. Factors considered included the patients' age, sex, the presence of pain, ageusia, hyperacusis, diabetes, hypertension, the progression and degree of palsy, the results of nerve excitability and salivary flow tests, and the time at which recovery was first noted or became complete. Bell's palsy remains without a proven efficacious treatment.", "The objective of this double-blind, randomized, placebo-controlled study was to test the efficacy of high-dose prednisone, administered as early as possible, in modifying the natural progression of Bell's palsy. Sixty-two consecutive patients, enrolled within 72 hours of facial palsy onset, were assigned to high dose intravenous prednisone in combination with intramuscular polyvitaminic therapy (group A) or polyvitaminic therapy alone (group B). Clinical grading of facial muscle strength and length of absence from work were evaluated. An early worsening of facial muscle strength was observed in controls, leading to the divergence in the trends of the grading scores in the two groups; this result was not confirmed in the long-term follow-up. Treated patients returned to work earlier than controls. In conclusion, early treatment based on high-dose corticosteroids slightly accelerates spontaneous improvement in Bell's palsy.", "Corticosteroids and antiviral agents are widely used to treat the early stages of idiopathic facial paralysis (i.e., Bell's palsy), but their effectiveness is uncertain.\n We conducted a double-blind, placebo-controlled, randomized, factorial trial involving patients with Bell's palsy who were recruited within 72 hours after the onset of symptoms. Patients were randomly assigned to receive 10 days of treatment with prednisolone, acyclovir, both agents, or placebo. The primary outcome was recovery of facial function, as rated on the House-Brackmann scale. Secondary outcomes included quality of life, appearance, and pain.\n Final outcomes were assessed for 496 of 551 patients who underwent randomization. At 3 months, the proportions of patients who had recovered facial function were 83.0% in the prednisolone group as compared with 63.6% among patients who did not receive prednisolone (P<0.001) and 71.2% in the acyclovir group as compared with 75.7% among patients who did not receive acyclovir (adjusted P=0.50). After 9 months, these proportions were 94.4% for prednisolone and 81.6% for no prednisolone (P<0.001) and 85.4% for acyclovir and 90.8% for no acyclovir (adjusted P=0.10). For patients treated with both drugs, the proportions were 79.7% at 3 months (P<0.001) and 92.7% at 9 months (P<0.001). There were no clinically significant differences between the treatment groups in secondary outcomes. There were no serious adverse events in any group.\n In patients with Bell's palsy, early treatment with prednisolone significantly improves the chances of complete recovery at 3 and 9 months. There is no evidence of a benefit of acyclovir given alone or an additional benefit of acyclovir in combination with prednisolone. (Current Controlled Trials number, ISRCTN71548196 [controlled-trials.com].).\n Copyright 2007 Massachusetts Medical Society.", "The therapeutic effect of corticosteroids in acute idiopathic peripheral nerve paralysis (Bell's palsy) in children is controversial. The authors evaluated the effect of steroids on the early and late outcome of children with Bell's palsy in a prospective randomized controlled setting. Forty-two patients (21 females, 21 males) with complete paralysis were enrolled in the study. Group 1 (n = 21) received methylprednisolone (1 mg/kg daily for 10 days orally); Group 2 (n = 21) did not. All patients were observed in the first 3 days of the disease and at 4, 6, and 12 months of follow-up. The mean age of Group 1 was 52.4 +/- 4.3 months, not significantly different from that of Group 2. In Group 1, 86% and 100% exhibited normal nerve function at 4 and 6 months of follow-up, respectively; in Group 2, 72% and 86% demonstrated complete recovery at 4 and 6 months, respectively, with improvement in all patients by 12 months. The improvement rates between the treated and untreated groups did not differ significantly. No side effects necessitated steroid withdrawal. The results of this study indicate that steroid therapy initiated at an early stage of childhood Bell's palsy does not significantly improve the outcome." ]

[ "17371357", "17709295", "9137848", "18268247", "21738025", "11985388", "19222595", "4905910", "511533" ]

[ "Low-dose topiramate versus lamotrigine in migraine prophylaxis (the Lotolamp study).", "Effects of levetiracetam vs topiramate and placebo on visually evoked phase synchronization changes of alpha rhythm in migraine.", "Lamotrigine versus placebo in the prophylaxis of migraine with and without aura.", "Oxcarbazepine in migraine headache: a double-blind, randomized, placebo-controlled study.", "Zonisamide versus topiramate in migraine prophylaxis: a double-blind randomized clinical trial.", "Efficacy and tolerability of acetazolamide in migraine prophylaxis: a randomised placebo-controlled trial.", "Evaluation of carisbamate for the treatment of migraine in a randomized, double-blind trial.", "Aetiology of migraine and prevention with carbamazepine (Tegretol): results of a double-blind, cross-over study.", "Clonazepam (rivotril) in migraine prophylaxis." ]

[ "To assess the efficacy and safety of topiramate and lamotrigine for prophylaxis in patients with frequent migraine as compared to each other and to placebo.\n Sixty patients with frequent migraine (more than 4 attacks per month) from the headache clinic at a tertiary referral centre in India were randomized to receive 50 mg topiramate/lamotrigine or matching placebo for 1 month each in 2 divided doses in 4 phases in a crossover manner with a washout period of 7 days in between. Primary efficacy measure was responder rate (50% decrease in mean migraine frequency/intensity). Secondary efficacy measures included reduction in mean monthly frequency, intensity, duration, rescue medication use, migraine associated symptoms, and adverse events.\n Analysis was on intention to treat basis. Data were analyzed as correlated data. Generalized estimation equation was used to compute overall mean standard deviation and 95% confidence intervals for each of the outcome variables. Bonferroni's correction done for multiple comparisons. P value of < .017 was taken as significant.\n Fifty-seven patients comprised the intent-to-treat population. Four patients withdrew from the study at various phases, none because of the side effects. Responder rate for frequency was significantly higher for topiramate versus placebo (63% vs 30%, P < .001), and versus lamotrigine (63% vs 46 %, P = .02). For intensity of headache also a responder rate of topiramate versus placebo (50% vs 10%, P < .001), and versus lamotrigine (50% vs 41%, P = .01) was observed. Topiramate showed statistically significant benefits (P < .017) in most of the secondary efficacy measures while lamotrigine was beneficial for reduction in headache frequency, and migraine associated symptoms. Adverse events were similar.\n Low-dose topiramate is efficacious in migraine prophylaxis as compared to both placebo and lamotrigine. Lamotrigine in low doses might be beneficial for headache frequency; however, longer trials are required to establish its efficacy on the intensity and frequency of migraine.", "Recent theories about migraine pathogenesis have outlined an abnormal central processing of sensory signals, also suggested by an abnormal pattern of EEG hyper-synchronization under visual stimulation. The aim of the present study was to test the efficacy of topiramate and levetiracetam vs placebo in a double blind project observing the effects of the three treatments on the EEG synchronization in the alpha band under sustained flash stimulation.\n Forty-five migraine without aura outpatients (MO) were selected and randomly assigned to 100mg topiramate, 1000 mg levetiracetam or placebo treatment. In addition, 24 non-migraine healthy controls were submitted to EEG analysis. The EEG was recorded by 19 channels: flash stimuli with a luminosity of 0.2J were delivered, in a frequency range from 3 to 30 Hz. We evaluated the phase synchronization index, that we previously applied in migraine, after EEG signals filtering in the alpha band. Our approach was based on the Hilbert transform.\n Both levetiracetam and topiramate significantly decreased migraine frequency, compared with placebo. MO patients displayed increased alpha-band phase synchronization as an effect of stimulus frequency; on the other hand the stimuli had an overall desynchronizing effect on control subjects. The phase synchronization index separates the two stages, before and after the treatment, only for levetiracetam, at stimulus frequencies of 9, 18, 24 and 27 Hz.\n An abnormal alpha band synchronization under visual stimuli was confirmed in migraine; this phenomenon was reversed by levetiracetam preventive treatment.\n These results confirmed in humans the inhibiting action of levetiracetam on neuronal hyper-synchronization.", "Lamotrigine blocks voltage-sensitive sodium channels, leading to inhibition of neuronal release of glutamate. Release of glutamate may be essential in the propagation of spreading cortical depression, which some believe is central to the genesis of migraine attacks. This study compared safety and efficacy of lamotrigine and placebo in migraine prophylaxis in a double-blind randomized parallel-groups trial. A total of 110 patients entered; after a 1-month placebo run-in period, placebo-responders and non-compliers were excluded, leaving 77 to be treated with lamotrigine (n = 37) or placebo (n = 40) for up to 3 months. Initially, lamotrigine therapy was commenced at the full dose of 200 mg/day, but, following a high incidence of skin rashes, a slow dose-escalation was introduced: 25 mg/day for 2 weeks, 50 mg/day for 2 weeks, then 200 mg/day. Attack rates were reduced from baseline means of 3.6 per month on lamotrigine and 4.4 on placebo to 3.2 and 3.0 respectively during the last month of treatment. Improvements were greater on placebo and these changes, not statistically significant, indicate that lamotrigine is ineffective for migraine prophylaxis. There were more adverse events on lamotrigine than on placebo, most commonly rash. With slow dose-escalation their frequency was reduced and the rate of withdrawal for adverse events was similar in both treatment groups.", "To evaluate the efficacy, safety, and tolerability of oxcarbazepine (1,200 mg/day) vs placebo as prophylactic therapy for patients with migraine headaches.\n This multicenter, double-blind, randomized, placebo-controlled, parallel-group trial consisted of a 4-week single-blind baseline phase and a 15-week double-blind phase consisting of a 6-week titration period, an 8-week maintenance period, and a 1-week down-titration period, after which patients could enter a 13-week open-label extension phase. During the 6-week titration period, oxcarbazepine was initiated at 150 mg/day and increased by 150 mg/day every 5 days to a maximum tolerated dose of 1,200 mg/day. The primary outcome measure was change from baseline in the number of migraine attacks during the last 28-day period of the double-blind phase.\n Eighty-five patients were randomized to receive oxcarbazepine and 85 to receive placebo. There was no difference between the oxcarbazepine (-1.30) and placebo groups in mean change in number of migraine attacks from baseline during the last 28 days of double-blind phase (-1.74; p = 0.2274). Adverse events were reported for 68 oxcarbazepine-treated patients (80%) and 55 placebo-treated patients (65%). The majority of adverse events were mild or moderate in severity. The most common adverse events (>or=15% of patients) in the oxcarbazepine-treated group were fatigue (20.0%), dizziness (17.6%), and nausea (16.5%); no adverse event occurred in more than 15% of the placebo-treated patients.\n Overall, oxcarbazepine was safe and well tolerated; however, oxcarbazepine did not show efficacy in the prophylactic treatment of migraine headaches.", "Topiramate is an antiepileptic drug that has been approved for migraine prophylaxis. Despite appropriate efficacy for migraine prophylaxis, some patients cannot tolerate its adverse effects. The aim of this study was to compare the efficacy of zonisamide, another antiepileptic drug, with topiramate in decreasing the frequency and severity of migraine attacks to determine whether it could be used as an alternative for noncompliant patients to topiramate.\n Eighty patients, recruited from referred migraineurs to our neurology clinic, who met the diagnosis and inclusion criteria were allocated randomly to group A (50-mg/d zonisamide, gradually titrated up to 200 mg/d) and group B (25-mg/d topiramate, gradually titrated up to 100 mg/d). Each patient was followed for 12 weeks and was assessed at entrance, in the fourth week and twelfth week for frequency of attacks, headache severity, need for acute medication, migraine disability assessment score, and adverse effects. A P < 0.05 was considered as the level of significant difference in all tests.\n Both drugs caused a significant decrease in frequency, severity, need for acute medication in migraine attacks, and migraine disability assessment score (P < 0.05). Except headache severity that was reduced significantly better by zonisamide (P < 0.008), there were no significant difference between the 2 groups in other items. Except for 2 cases of intolerable paresthesia, both drugs were tolerated well during the study.\n Our results indicated that zonisamide is as effective as topiramate in migraine prophylaxis and can be considered as an alternative treatment when topiramate is not tolerated well.", "Familial hemiplegic migraine and episodic ataxia type 2 (EA2) are allelic disorders with distinct types of mutations in the CACNA1A gene. EA2 attacks are remarkably sensitive to acetazolamide, a carbonic anhydrase inhibitor. The effectiveness of acetazolamide in migraine prophylaxis is unknown.\n To evaluate the efficacy and the tolerability of acetazolamide in migraine prophylaxis.\n We compared daily oral 500 mg acetazolamide and placebo in patients with migraine in a multicentre, double-blind, randomised trial of 12 weeks duration after a run-in period of 4 weeks without treatment. Frequency of attacks at the last trial period of 4 weeks was the primary efficacy criterion. Secondary efficacy criteria were the frequency of attacks per 4 weeks, the severity and duration of attacks, the number of hours with migraine as well as the number of responders with more than 50% reduction in attack frequency.\n 53 patients had been enrolled when the study was prematurely stopped because of a high number of withdrawals (34%), primarily linked to acetazolamide related side effects. Considering the primary and secondary efficacy criteria, among the 53 included patients (27 in the placebo group and 26 in the acetazolamide group), no difference between the 2 study groups could be demonstrated. The most frequent adverse events related to acetazolamide were paresthesias and asthenia.\n In this trial, migraine sufferers poorly tolerated acetazolamide given in an oral dose of 500 mg daily. No obvious prophylactic beneficial effect of acetazolamide appeared on migraine attacks.", "This study explored the dose-response relationship of carisbamate administered at doses of 100 mg per day, 300 mg per day, or 600 mg per day, in the prevention of migraine.\n Carisbamate ([S]-2-O-carbamoyl-1-o-chlorophenyl-ethanol; RWJ 333369) is a new chemical entity being studied for efficacy as adjunctive therapy in partial onset epilepsy. Because some antiepileptic drugs are also efficacious in migraine, for example, topiramate and valproate sodium, we tested carisbamate in migraine prophylaxis.\n This was a double-blind, placebo-controlled trial, approximately 22-week duration. The primary efficacy variable was the percent reduction from baseline through the double-blind phase in average monthly migraine frequency using a 48-hour rule. Patients were randomized 1 : 1 : 1 : 1 to treatment with carisbamate 100, 300, or 600 mg per day, or placebo. Migraine attacks were counted during a prospective 4-week baseline period, which was followed by a 2-week titration period, a 12-week maintenance period, a 1-week medication reduction period, and a 3-week observation period. Patients had an established history of migraine, with or without aura, for at least 1 year and a 3-month history of 3-12 migraine attacks per month.\n Patients (n = 323) were predominantly women (85%) and white (89%); mean age was 41 years. There were no statistically significant differences between any of the carisbamate groups and placebo (P > or = .6) for the median (range) percentage reduction from baseline to end point in average monthly migraine frequency (P value vs placebo): 37% (-250%, 100%) for placebo; 33% (-210%, 100%; P = .7) CRS 100 mg/day; 27% (-100%, 100%; P = .8) CRS 300 mg/day; and 35% (-87%, 100%; P = .6) CRS 600 mg/day. Results for secondary efficacy measures (responder rate, percent reduction in average monthly migraine frequency using the 24-hour rule, and percent reduction in average monthly migraine days) were consistent (P > or = .075). The proportion of patients discontinuing because of adverse events was similar for placebo and carisbamate-treated patients (13% each). The most common (occurring in > or =5% of patients) treatment-emergent adverse events in patients treated with carisbamate were fatigue (17%) and nasopharyngitis (13%). Fatigue appeared to be dose related.\n Carisbamate was not more efficacious in migraine prophylaxis than placebo in this well-controlled study that included a suitable population. However, carisbamate monotherapy was well tolerated at doses up to 600 mg per day.", "nan", "nan" ]

[ "11342473" ]

[ "Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy." ]

[ "This prospective placebo-controlled trial was designed to determine whether intravenous immune globulin (IVIG) improves left ventricular ejection fraction (LVEF) in adults with recent onset of idiopathic dilated cardiomyopathy or myocarditis.\n Sixty-two patients (37 men, 25 women; mean age +/-SD 43.0+/-12.3 years) with recent onset (</=6 months of symptoms) of dilated cardiomyopathy and LVEF </=0.40 were randomized to 2 g/kg IVIG or placebo. All underwent an endomyocardial biopsy before randomization, which revealed cellular inflammation in 16%. The primary outcome was change in LVEF at 6 and 12 months after randomiz. Overall, LVEF improved from 0.25+/-0.08 to 0.41+/-0.17 at 6 months (P<0.001) and 0.42+/-0.14 (P<0.001 versus baseline) at 12 months. The increase was virtually identical in patients receiving IVIG and those given placebo (6 months: IVIG 0.14+/-0.12, placebo 0.14+/-0.14; 12 months: IVIG 0.16+/-0.12, placebo 0.15+/-0.16). Overall, 31 (56%) of 55 patients at 1 year had an increase in LVEF >/=0.10 from study entry, and 20 (36%) of 56 normalized their ejection fraction (>/=0.50). The transplant-free survival rate was 92% at 1 year and 88% at 2 years.\n These results suggest that for patients with recent-onset dilated cardiomyopathy, IVIG does not augment the improvement in LVEF. However, in this overall cohort, LVEF improved significantly during follow-up, and the short-term prognosis remains favorable." ]

[ "3071485", "629924", "9423499", "9314625", "9301427", "2064484", "2209318", "7942937", "11078048", "11140007", "8612437", "9279482", "6391877", "10919939", "8949977", "7040142", "3302144", "8112194" ]

[ "Exercise in a behavioural weight control programme for obese patients with Type 2 (non-insulin-dependent) diabetes.", "Prospective comparison of modified fat-high-carbohydrate with standard low-carbohydrate dietary advice in the treatment of diabetes: one year follow-up study.", "Long-term effects and costs of brief behavioural dietary intervention for patients with diabetes delivered from the medical office.", "A randomized controlled trial of weight reduction and exercise for diabetes management in older African-American subjects.", "Effects of physical training on metabolic control in elderly type 2 diabetes mellitus patients.", "Effects of a very-low-calorie diet on long-term glycemic control in obese type 2 diabetic subjects.", "Impact of intensive educational approach to dietary change in NIDDM.", "Year-long weight loss treatment for obese patients with type II diabetes: does including an intermittent very-low-calorie diet improve outcome?", "Brief, computer-assisted diabetes dietary self-management counseling: effects on behavior, physiologic outcomes, and quality of life.", "A diabetes management program for African American women with type 2 diabetes.", "Effects of a behavioral weight loss program stressing calorie restriction versus calorie plus fat restriction in obese individuals with NIDDM or a family history of diabetes.", "Will older sedentary people with non-insulin-dependent diabetes mellitus start exercising? A health promotion model.", "A four-year prospective trial of unmeasured diet in lean diabetic adults.", "Comparison of high- and low-glycemic-index breakfast cereals with monounsaturated fat in the long-term dietary management of type 2 diabetes.", "Early lifestyle intervention in patients with non-insulin-dependent diabetes mellitus and impaired glucose tolerance.", "A randomised controlled trial of the effect of low fat diet advice on dietary response in insulin independent diabetic women.", "Effects of diet and exercise interventions on control and quality of life in non-insulin-dependent diabetes mellitus.", "Long-term comparison of three dietary prescriptions in the treatment of NIDDM." ]

[ "Two studies were conducted to determine whether adding exercise to a diet programme promotes weight loss or glycaemic control in Type 2 (non-insulin-dependent) diabetic subjects. In Study 1, 25 subjects were randomly assigned to diet plus moderate exercise or diet plus placebo exercise. All subjects exercised twice a week as a group and once a week on their own; the diet plus moderate exercise group walked a 3-mile route at each session while the diet plus placebo exercise group did very low intensity exercises such as stretching and light calisthenics. All subjects followed a calorie-counting diet and were taught behaviour modification strategies. Weight losses and improvements in glycaemic control did not differ significantly between the two treatment groups at the end of the 10-week treatment or at 1-year follow-up. In Study 2, more extreme conditions were compared: a diet only group and a diet plus exercise group. The diet plus exercise group walked a 3-mile route with the group 3 times/week and once a week on their own, while the diet only group was instructed to maintain their current low level of activity. Both groups received comparable diet and behaviour modification instruction and therapist contacts. The diet plus exercise group had significantly (p less than 0.01) better weight losses than the diet only condition at the end of the 10 week programme (-9.3 kg vs -5.6 kg) and at 1 year follow-up (-7.9 kg vs -3.8 kg).(ABSTRACT TRUNCATED AT 250 WORDS)", "1. A prospective randomized study of two dietary regimens has been started in newly-diagnosed diabetics to determine their effect on circulating metabolites and on diabetic complications. 2. During the first year of treatment the fasting plasma glucose concentrations on both the low-carbohydrate diet and the high-carbohydrate, modified-fat (MF) diet showed a similar decrease. 3. Plasma cholesterol showed a sustained decrease only in patients recommended a MF diet. Transient changes in plasma triglyceride concentrations occurred in patients on both dietary regimens. 4. Increased plasma cholesterol levels are associated with atheromatous disease which is common in diabetics in Europe and North America. A MF diet may therefore have an advantage in that it lowers the plasma cholesterol as well as being effective in lowering the plasma glucose.", "This study evaluated the 12-month follow-up results and costs of a personalized, medical office-based intervention focused on behavioral issues related to dietary self-management. Two hundred and six adults having diabetes attending an internal medicine outpatient clinic visit were randomized to either Usual Care or to Brief Intervention. The single session intervention involved touchscreen computer-assisted assessment that provided immediate feedback on key barriers to dietary self-management, goal setting and problem-solving counselling. Follow-up components included phone calls and videotape intervention relevant to each participant. Brief Intervention produced significantly greater improvement than Usual Care on multiple measures of change in dietary behaviour (e.g., covariate adjusted difference of 2.2% of calories from fat; p = 0.023) and on serum cholesterol levels (covariate adjusted difference of 15 mg/dl; p = 0.002) at 12-month follow-up. There were also significant differences favouring intervention on patient satisfaction (p < 0.02) but not on HbA1c levels. The costs of intervention ($137 per patient) were modest relative to many commonly used practices.", "To evaluate a weight loss and exercise program designed to improve diabetes management in older African-Americans.\n Overweight African-Americans (n = 64) ages 55-79 years with NIDDM were randomized to either an intervention (12 weekly group sessions, 1 individual session, and 6 biweekly group sessions) or usual care (1 individual session, and 6 biweekly group sessions) or usual care (1 class and 2 informational mailings). Clinical and behavioral variables were assessed at 0, 3, and 6 months of treatment.\n Significant net differences in the intervention versus usual care were observed for weight (-2.0 kg, P = 0.006), physical activity, and dietary intake of fat, saturated fat, cholesterol, and nutrition knowledge at 3 months (all P < 0.05) and for weight at 6 months (-2.4 kg; P = 0.006) and mean HbA1c values at 3 and 6 months (respectively, -1.6 and -2.4%, both P < 0.01). After the adjustment for changes in weight and activity, the intervention participants were approximately twice as likely to have a one unit decrease in HbA1c value as those in usual care. Blood pressure increase sin usual care participants resulted in net differences (intervention minus control) at 3 and 6 months of -3.3 (P = 0.09) and -4.0 (P = 0.05) mmHg diastolic, respectively, and -8.4 (P = 0.06) and -5.9 (P > 0.10) mmHg systolic, respectively. Blood lipid profiles improved more in intervention than usual care participants, but not significantly.\n The intervention program was effective in improving glycemic and blood pressure control. The decrease in HbA1c values was generally independent of the relatively modest changes in dietary intake, weight, and activity and may reflect indirect program effects on other aspects of self-care.", "1. The specific role of physical activity in the treatment of type 2 diabetes is still subject to discussion. A randomized prospective study was performed, investigating both the influence of physical training on metabolic control and the feasibility of physical training in the elderly. 2. A total of 58 patients (mean age: 62 +/- 5 years; range: 55-75 years) with type 2 diabetes were randomized to either a physical training or a control programme. The training programme consisted of three sessions a week, aiming at 60-80% of the maximal oxygen uptake (VO2max). The 12 week supervised period was followed by a 14 week non-supervised one. The control group followed an educational programme. VO2max was assessed during exercise on a cycle ergometer. Glycosylated haemoglobin (HbA1c) was used as a measure for glucose control, and an insulin tolerance test was performed to test insulin sensitivity. Multivariate analysis of variance, with repeated measures design, was used to test differences between groups. 3. Fifty-one patients completed the study. VO2max was higher in the training group than in the control group both after 6 weeks (P < or = 0.01 between groups) and after 26 weeks [training group: 1796 +/- 419 ml/min (prestudy), 1880 +/- 458 ml/min (6 weeks), 1786 +/- 591 ml/min (26 weeks); control group: 1859 +/- 455 ml/min (prestudy), 1742 +/- 467 ml/min (6 weeks), 1629 +/- 504 ml/min (26 weeks)]. Blood glucose control and insulin sensitivity did not change during the study. Levels of total triacylglycerols, very-low-density lipoprotein-triacylglycerols and apolipoprotein B were significantly lower after 6 weeks (P < or = 0.01, P < or = 0.05, P < or = 0.05 between groups respectively), and so was the level of total cholesterol after 12 weeks of training (P < or = 0.05 between groups). 4. Physical training in obese type 2 diabetic patients over 55 years of age does not change glycaemic control or insulin sensitivity in the short-term. Regular physical activity may lower triacylglycerol and cholesterol levels in this group of patients. 5. Finally, physical training in motivated elderly type 2 diabetic patients without major cardiovascular or musculoskeletal disorders is feasible, but only under supervision.", "We tested the hypothesis that the use of a very-low-calorie diet (VLCD) in combination with behavior modification would promote long-term glycemic control in obese type 2 diabetic subjects. Thirty-six diabetic subjects were randomly assigned to a standard behavior therapy program or to a behavior therapy program that included an 8-week period of VLCD. The behavior therapy group consumed a balanced diet of 4200 to 6300 J/d throughout the 20-week program. The VLCD group consumed a balanced diet of 4200 to 6300 J for weeks 1 to 4, followed by a VLCD (1680 J/d of lean meat, fish, and fowl) for weeks 5 to 12. The VLCD group then gradually reintroduced other foods during weeks 13 to 16 and consumed a balanced diet of 4200 to 6300 J/d for weeks 17 to 20. Thirty-three of the 36 subjects completed the 20-week program and the 1-year follow-up. Use of the VLCD produced greater decreases in fasting glucose at the end of the 20-week program and at 1-year follow-up and greater long-term reductions in HbA1. The VLCD group also had greater weight losses at week 20, but weight losses from pretreatment to 1-year follow-up were similar in the two treatment groups. The improved glycemic control with the VLCD appeared to be due to increased insulin secretion, but further research is needed to confirm this.", "The aim of this study was to compare the effects of an intensive educational approach incorporating longer time, greater simplicity, repetition, and cognitive motivational techniques with a conventional one in subjects with established non-insulin-dependent diabetes mellitus (NIDDM) whose weight, glycemic control, and diet were not optimal. Subjects were randomly allocated to intensive or conventional education. Of 350 subjects, 70 met the study criteria, which included established NIDDM (greater than or equal to 3 mo), suboptimal recent glycemic control, dietary fat intake greater than or equal to 35% of total energy intake, and body mass index greater than or equal to 25 kg/m2. The intensive approach was associated with significantly greater improvements in dietary compliance, dietary intake (complex carbohydrate, [P = 0.013], legumes [P less than 0.0001], fiber [P less than 0.0001], total fat [P less than 0.004], saturated fat [P less than 0.004]), and total cholesterol level (P = 0.007). The transient improvement in glycemic control was similar in both groups. An intensive education program can improve dietary compliance in established NIDDM subjects more than a conventional one. These recommended dietary improvements achieve better improvement in total cholesterol but do not necessarily improve glycemic control.", "To evaluate a year-long behavioral weight control program, used with and without an intermittent very-low-calorie diet (VLCD) in the treatment of type II diabetes mellitus.\n Subjects (n = 93) were randomly assigned to 50-week treatment programs that used either a balanced low-calorie diet (LCD) of 1,000 to 1,000 kilocalories (kcal) per day throughout or included 2 12-week periods of a VLCD of 400 to 500 kcal per day alternating with the balanced LCD. Weight, glycemic control, blood pressure, and lipids were assessed at baseline, at the end of the year-long treatment, and at 2-year follow-up.\n Subjects in the VLCD program lost significantly more weight than did LCD subjects at the end of the 50-week program (14.2 kg versus 10.5 kg; P = 0.057) and remained off diabetes medication longer (P < 0.05). These benefits of the VLCD were due primarily to the first 12 weeks of the diet; the second diet maintained, but did not increase, these effects. Subjects in both groups experienced marked improvements in glycemic control and cardiovascular risk factors over the year-long program, but attendance declined in the latter weeks of treatment and weight was regained. There was also marked recidivism in both groups in the year following treatment.\n The intermittent VLCD improved weight loss and glycemic control, but these effects were quite modest and do not appear to justify the clinical use of an intermittent VLCD. Moreover, lengthening treatment to a full year did not prevent relapse. Thus, further research is needed to develop a successful approach to long-term weight control.", "The objective of this work was to evaluate the reach, effectiveness, adoption, and implementation of a brief behavioral dietary intervention and 2 supplemental components of diabetes self-management support: telephone follow-up calls and community resources enhancement.\n This was a 2 x 2 randomized, controlled trial investigating the incremental effects of telephone follow-up and community resources enhancement with 320 adult type 2 diabetes outpatients. METHODS. Key outcomes included behavioral (dietary patterns, fat intake), physiologic (HbA1c, lipids), and quality-of-life/patient satisfaction measures and were collected at baseline and 3- and 6-month follow-up.\n Despite high reach (76% patient participation), excellent adoption (all 12 primary care practices approached participated), and good implementation, there were few outcome differences among treatment conditions. There was significant improvement across conditions in most outcomes in each category at both follow-ups.\n A brief, computer-assisted, dietary goal-setting intervention basic treatment condition was moderately successful in producing dietary improvements but less so in producing biologic or quality-of-life outcomes. Additions of follow-up phone calls or a community resources enhancement component did not produce incremental improvements over this basic intervention.", "This paper describes a clinic- and community-based diabetes intervention program designed to improve dietary, physical activity, and self-care behaviors of older African American women with type 2 diabetes. It also describes the study to evaluate this program and baseline characteristics of participants.\n The New Leaf ... Choices for Healthy Living With Diabetes program consists of 4 clinic-based health counselor visits, a community intervention with 12 monthly phone calls from peer counselors, and 3 group sessions. A randomized, controlled trial to evaluate the effectiveness of this intervention is described.\n Seventeen focus groups of African American women were used to assessed the cultural relevance/acceptability of the intervention and measurement instruments. For the randomized trial, 200 African American women with type 2 diabetes were recruited from 7 practices in central North Carolina. Mean age was 59, mean diabetes duration was 10 years, and participants were markedly overweight and physically inactive.\n Participants found this program to be culturally relevant and acceptable. Its effects on diet, physical activity, and self-care behaviors will be assessed in a randomized trial.", "The aim of this randomized trial was to compare the effects of a behavioral intervention focusing on either calorie restriction alone or calorie plus fat restriction on weight loss and changes in lipids and glycemic control in individuals with non-insulin-dependent diabetes mellitus (NIDDM) or a family history of diabetes.\n We recruited 44 obese women with NIDDM and 46 obese women with a family history of NIDDM and randomly assigned these subjects to calorie restriction (CAL) or to calorie plus fat restriction (CAL + FAT). All subjects participated in a 16-week behavioral weight loss program, with training in diet, exercise, and behavior modification. Subjects assigned to the CAL condition were given a 1,000-1,500 kcal/day goal and self-monitored calories consumed. Subjects assigned to the CAL+FAT condition had the same calorie goal, but were also given a fat goal (grams of fat/day), to produce a diet with < 20% of calories from fat; this group monitored both calories and fat grams.\n Among NIDDM subjects, weight loss of the subjects in the CAL+FAT condition was significantly greater than subjects in the CAL condition (7.7 vs. 4.6 kg) and the CAL+FAT condition group also maintained their weight loss better at the 1-year follow-up (5.2 vs. 1.0 kg). Significant decreases in glucose, high-density lipoprotein (HDL) cholesterol, and total cholesterol were seen after 16 weeks of treatment among NIDDM subjects; these changes were similar in CAL and CAL+FAT groups, but a greater proportion of subjects in CAL condition required oral hypoglycemic medication. At the 1-year follow-up, all parameters had returned to baseline. No significant differences in weight loss or physiological changes were seen between CAL and CAL+FAT conditions in subjects with a family history of diabetes.\n These results suggest that using the combination of calorie and fat restriction may help promote weight loss in obese NIDDM patients. No other long-term benefits of this regimen were observed.", "Exercise and diet are the cornerstones of management of non-insulin-dependent diabetes mellitus (NIDDM). Many older people have difficulty in exercising, missing benefits on glycaemic control, weight, cardiac disease and mood. We report the outcomes of a 6 month structured exercise and support programme based on a health promotion model, on physical activity, glycaemic control and parameters of cardiovascular risk in non-exercisers, compared with standard outpatient clinic education. A total of 26 non-exercising patients were randomised to an intervention or control group (ten men, 16 women; mean age (+/- S.D.) 60 +/- 8 years). Programme participation was not associated with any significant increase in activity. Glycated hemoglobin (HbAtc) levels tended to stabilise in the intervention group during the 6 month programme and to deteriorate in the control group (P = 0.03); by 12 months HbA1C levels deteriorated to a similar level in both. Programme participation did not cause significant change in anthropometric or metabolic parameters. Examining the cohort as a whole, increased activity over 6 months was associated with improvements in weight, body mass index (BMI), body fat and fasting insulin. Activity increases over 12 months were associated with improvements in weight and BMI. These changes could not be attributed to changes in energy intake or dietary composition. We conclude that while exercise can benefit older people with NIDDM, a programme based on a model of health promotion was not effective in increasing physical activity.", "Fifty-one adult male outpatients at or below ideal body weight (IBW) with no history of weighing more than 15% over IBW in the past 5 yr and no more than 25% in the past 15 yr were randomly assigned to a traditional calorically defined exchange-type diet (EXCH) or an unmeasured diet emphasizing avoidance of refined sugar and balance of food consumption throughout the day. All but 4 patients were insulin treated. With the exception of one patient in each group, all patients were classified as having type II diabetes. Subjects were followed in a single-blind design for 4 yr in the Diabetes Outpatient Clinic every 3 mo. The average mean fasting glycemia (FBS), coefficient of FBS variation, number of reported hypoglycemic reactions, mean fasting serum triglyceride and cholesterol levels, and mean total daily insulin dosage were similar in both groups. Each patient's mean daily caloric intake did vary over time, but there was no difference in mean caloric intake between diet groups. There was a significant correlation between a patient's mean FBS rating and his serum triglyceride level: patients with lower mean FBS had a significantly lower mean triglyceride level than patients with higher FBS. Overall body weights remained stable throughout the study. However, there was a significant difference in the number of patients in the EXCH group whose actual weight was 3% or more above IBW on 50% or more of their visits.(ABSTRACT TRUNCATED AT 250 WORDS)", "Results of 6-wk studies suggest that high-carbohydrate diets are deleterious for people with type 2 diabetes.\n Our objective was to see whether long-term replacement of dietary monounsaturated fatty acids (MUFAs) with carbohydrate from breakfast cereals with either a high or a low glycemic index (GI) affected blood glucose and lipids in subjects with type 2 diabetes.\n Subjects with type 2 diabetes (n = 91) were randomly assigned to receive approximately 10% of energy from a low-GI breakfast cereal, a high-GI cereal, or oil or margarine containing MUFA for 6 mo. Eating breakfast cereal was prohibited for subjects in the MUFA group.\n Seventy-two subjects completed the trial. The subjects who received cereals consumed approximately 10% more energy from carbohydrate than did the subjects in the MUFA group. Changes in glycated hemoglobin, body weight, and fasting cholesterol and triacylglycerol did not differ significantly among groups. HDL cholesterol increased by approximately 10% in the MUFA group compared with subjects who consumed either high- or low-GI cereals (P = 0.002). The ratio of total to HDL cholesterol was higher in the subjects who consumed the high-GI cereal than in the MUFA group at 3 mo but not at 6 mo (diet x time interaction, P = 0.041). During 8-h metabolic profiles, mean plasma insulin was higher and mean free fatty acids were lower in the 2 cereal groups than in the MUFA group (P < 0.05).\n A 10% increase in carbohydrate intake associated with breakfast cereal consumption had no deleterious effects on glycemic control or blood lipids over 6 mo in subjects with type 2 diabetes. The increase in plasma insulin and the reduction in free fatty acids associated with higher carbohydrate intake may reduce the rate of progression of diabetes.", "Non-insulin-dependent diabetes mellitus (NIDDM) is preceded by impaired glucose tolerance (IGT) lasting for years before manifesting as overt hyperglycaemia. Both genetic and environmental factors contribute to the development of IGT and NIDDM. Obesity, physical inactivity and high-fat diet have been found to predict IGT and NIDDM. Therefore, a diet and exercise intervention from diagnosis of NIDDM could improve the treatment outcome and prognosis of patients with NIDDM. Furthermore, because subjects with IGT are at increased risk for diabetes and atherosclerotic vascular disease, it is reasonable to assume that in terms of reducing the incidence and longterm consequences of NIDDM an intervention at this phase is more effective than in overt diabetes. Although the nonpharmacological approach is generally accepted as the first-line treatment of NIDDM its efficacy has often been questioned. Therefore, it is important to carry out long-term controlled studies to find out to what extent lifestyle modification could improve the metabolic control and level of major cardiovascular risk factors known to be associated with poor outcome in NIDDM. This kind of study also gave relevant experience in planning studies aiming at primary prevention of NIDDM. One-year dietary and exercise intervention on newly diagnosed NIDDM patients in Kuopio, Finland resulted in a better metabolic control and a moderate reduction in cardiovascular risk factors as compared to the conventional treatment group. After the second year of follow-up only 12.5% in the intervention group were receiving oral antidiabetic drugs vs. 34.8% in the conventional treatment group. Weight reduction and a reduced use of saturated fats appeared to be the main determinants of successful treatment results. Good aerobic capacity was associated with an increase in HDL cholesterol. A multicentre primary prevention study on IGT patients is continuing in Finland applying the same principles of intervention as used in the study on newly diagnosed NIDDM patients. Pilot results show that glucose tolerance can be improved by lifestyle changes.", "Type 2 (insulin independent) diabetic women were randomly allocated to receive advice for low fat diets or low carbohydrate diets. By 24 h weighted dietary intakes before and after a mean interval of six months, patients in the low fat group had reduced their fat intake from 41% to 31% of total energy, while carbohydrate percentage of total energy intake increased from 38% to 46%. Percentage energy intake from fat and carbohydrate in the control group remained unchanged. Body weight fell in both groups especially for patients in the low fat group who were obese (weight/height2 greater than or equal to 28 kg/m2). Mean plasma glucose, HbA1, and triglycerides were unchanged. Mean plasma total cholesterol fell significantly in the low fat group compared with the controls (p less than 0.001), but there was no significant difference in the small reduction of high density lipoprotein cholesterol observed in both groups. Thus, adherence to low fat diets occurred without deterioration of diabetes and with benefit for weight and total cholesterol.", "Evidence suggests that diet and exercise are associated with improved glucose tolerance for patients with non-insulin-dependent diabetes mellitus (NIDDM). Seventy-six volunteer adult patients with NIDDM were each assigned to one of four programs: diet, exercise, diet plus exercise, or education (control). Each program required ten weekly meetings. Detailed evaluations were completed prior to the program and after three, six, 12, and 18 months. Evaluations included various psychosocial measures, measures of the quality of life, and fasting blood glucose, glycosylated hemoglobin, and relative weight determinations. Of the 76 original participants, 70 completed the 18-month follow-up study. At 18 months, the combination diet-and-exercise group had achieved the greatest reductions in glycosylated hemoglobin measures. In addition, this group showed significant improvements on a general quality of life measure. These improvements were largely uncorrelated with changes in weight. The authors conclude that the combination of dietary change and physical conditioning benefits NIDDM patients, and that the benefits may be independent of substantial weight loss.", "To compare three sets of dietary guidelines for the treatment of non-insulin-dependent diabetes (NIDDM) in free-living individuals and to observe the effects on metabolic control over an 18-month period.\n Seventy volunteer subjects with NIDDM were randomly assigned to one of three diets, a weight-management diet, a high-carbohydrate/fiber diet, or a modified-lipid diet and followed for 18 months. Nutrient intakes, weight, blood lipids, and glycemic control were measured.\n In all diet groups, glycated hemoglobin (HbA1) fell significantly before diet intervention began, remaining lower throughout the study and at follow-up 9 months later. Low-density lipoprotein (LDL) cholesterol showed a sustained fall in all groups after diet intervention. Apart from transient changes in high-density lipoprotein (HDL) cholesterol and triglyceride (TG) in the diet groups with the higher carbohydrate intake, no lasting differences were found between the three diet groups.\n In the long term, there were few differences in the outcome of the three dietary prescriptions. Even with intensive instruction, participants found it difficult to meet recommended nutrient intakes; however, specific dietary advice did result in an improvement in LDL cholesterol. Adverse changes in HDL cholesterol and TG because of diet intervention were transient. The significant improvement in glycemic control during the recruitment phase may have been the result of participants' previous dietary knowledge and the increased attention that they received during the intervention." ]

[ "19092238", "18096840", "16685123", "17434094", "19834016" ]

[ "Pragmatic management of hyperglycaemia in acute ischaemic stroke: safety and feasibility of intensive intravenous insulin treatment.", "Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial.", "A randomised, controlled pilot study to investigate the potential benefit of intervention with insulin in hyperglycaemic acute ischaemic stroke patients.", "Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK).", "Glucose Regulation in Acute Stroke Patients (GRASP) trial: a randomized pilot trial." ]

[ "In patients with acute ischaemic stroke, hyperglycaemia has been retrospectively associated with negative outcome. There is an ongoing discussion as to which treatment algorithm, if any, provides the most effective prospective intervention. Here we test the safety and feasibility of an intravenous insulin-only infusion protocol designed for pragmatic routine clinical use.\n 40 ischaemic stroke patients with onset <24 h ago, admitted to our stroke unit, were randomized either to the study regimen (50 IU insulin in 50 ml 0.9% saline solution applied intravenously via a perfusor pump), with the aim of reaching and maintaining blood glucose levels between 4.44 mmol/l (80 mg/dl) and 6.11 mmol/l (110 mg/dl), or were treated with insulin subcutaneously if concentrations were above 11.10 mmol/l (200 mg/dl). Treatment was continued for 5 days. Primary outcome was the number of hypoglycaemic (<3.33 mmol/l; <60 mg/dl) and severe hyperglycaemic (>16.65 mmol/l; >300 mg/dl) events.\n Hypoglycaemic events were significantly more common in patients treated intensively (total n = 25; incidence rate ratio, IRR = 5.3; 95% CI = 1.2-22.4; p < 0.05). Symptomatic events were rare (total n = 5). Severe hyperglycaemia was associated with conventional treatment (IRR = 4.9; 95% CI = 1.5-15.9; p < 0.05). Though those treated intensively attained near-normoglycaemic levels quicker and had significantly lower blood glucose levels over the study period (6.49 +/- 2.19 mmol/l vs. 8.01 +/- 3.06 mmol/l; 95% CI = -1.78 to -1.28, p < 0.0005), treatment imposes considerable strain on both patients and caregivers.\n The intensive intravenous insulin infusion protocol effectively lowers blood glucose levels with an increased risk of manageable hypoglycaemic events. However, a highly motivated and trained staff seems essential, limiting feasibility outside of specialty care settings.\n Copyright (c) 2008 S. Karger AG, Basel.", "Hyperglycemia may worsen brain injury during acute cerebral infarction. We tested the feasibility and tolerability of aggressive hyperglycemia correction with intravenous insulin compared with usual care during acute cerebral infarction.\n We conducted a randomized, multicenter, blinded pilot trial for patients with cerebral infarction within 12 hours after onset, a baseline glucose value >or=8.3 mmol/L (>or=150 mg/dL), and a National Institutes of Health Stroke Scale score of 3 to 22. Patients were randomized 2:1 to aggressive treatment with continuous intravenous insulin or subcutaneous insulin QID as needed (usual care). Target glucose levels were <7.2 mmol/L (<130 mg/dL) in the aggressive-treatment group and <11.1 mmol/L (<200 mg/dL) in the usual-care group. Glucose was monitored every 1 to 2 hours, and the protocol treatments continued for up to 72 hours. Final clinical outcomes were assessed at 3 months.\n We randomized 46 patients (31 to aggressive treatment and 15 to usual care). All patients in the aggressive-treatment group and 11 (73%) in the usual-care group had diabetes (P=0.008). Glucose levels were significantly lower in the aggressive-treatment group throughout protocol treatment (7.4 vs 10.5 mmol/L [133 vs 190 mg/dL], P<0.001). Hypoglycemia <3.3 mmol/L (<60 mg/dL) occurred only in the aggressive-treatment group (11 patients, 35%), 4 (13%) of whom had brief symptoms, including only 1 (3%) neurologic. Final clinical outcomes were nonsignificantly better in the aggressive-treatment group.\n The intravenous insulin protocol corrected hyperglycemia during acute cerebral infarction significantly better than usual care without major adverse events and should be investigated in a clinical efficacy trial.", "Hyperglycaemia on presentation with acute ischaemic stroke (AIS) is associated with poor outcome, but intervention is unproven. We investigated the safety and tolerability of one method of glycaemic control.\n Patients within 24 h of AIS and plasma glucose 8-20 mmol/l were randomised to receive either rigorous glycaemic control (RC) or standard management (SM) for 48 h. RC comprised i.v. insulin at a variable rate adjusted for target glucose concentration of 5-8 mmol/l, and intravenous crystalloid. The SM group received intravenous crystalloid alone in an open-label design.\n Thirteen patients were randomised to RC and 12 to SM (age 75 +/- 6.2 years; 40% male; 20% lacunar stroke; time to treatment 8 +/- 6.1 h; plasma glucose 10.6 +/- 0.9 mmol/l; known diabetes 52%; NIHSS 8, range 2-28). The glucose concentration-time curve was reduced in the RC group (AUC 324 +/- 15 versus 385 +/- 28 h.mmol/l, p = 0.04). By 48 h, plasma glucose in both groups was 6.8 +/- 1.1 and 7.5 +/- 1.3 mmol/l respectively, but mean hourly insulin requirements in the RC group had dropped from 3.25 +/- 0.32 units to 1.25 +/- 0.5 units (p < 0.01). One transient episode of hypoglycaemic symptoms occurred in the RC group.\n Glycaemic control with sliding scale insulin for 48 h is feasible and well-tolerated after AIS. Treatment after 48 h may be unnecessary.\n Copyright 2006 S. Karger AG, Basel.", "Hyperglycaemia after acute stroke is a common finding that has been associated with an increased risk of death. We sought to determine whether treatment with glucose-potassium-insulin (GKI) infusions to maintain euglycaemia immediately after the acute event reduces death at 90 days.\n Patients presenting within 24 h of stroke onset and with admission plasma glucose concentration between 6.0-17.0 mmol/L were randomly assigned to receive variable-dose-insulin GKI (intervention) or saline (control) as a continuous intravenous infusion for 24 h. The purpose of GKI infusion was to maintain capillary glucose at 4-7 mmol/L, with no glucose intervention in the control group. The primary outcome was death at 90 days, and the secondary endpoint was avoidance of death or severe disability at 90 days. Additional planned analyses were done to determine any differences in residual disability or neurological and functional recovery. The trial was powered to detect a mortality difference of 6% (sample size 2355), with 83% power, at the 5% two-sided significance level. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN 31118803)\n The trial was stopped due to slow enrolment after 933 patients were recruited. For the intention-to-treat data, there was no significant reduction in mortality at 90 days (GKI vs control: odds ratio 1.14, 95% CI 0.86-1.51, p=0.37). There were no significant differences for secondary outcomes. In the GKI group, overall mean plasma glucose and mean systolic blood pressure were significantly lower than in the control group (mean difference in glucose 0.57 mmol/L, p<0.001; mean difference in blood pressure 9.0 mmHg, p<0.0001).\n GKI infusions significantly reduced plasma glucose concentrations and blood pressure. Treatment within the trial protocol was not associated with significant clinical benefit, although the study was underpowered and alternative results cannot be excluded.", "Hyperglycemia is associated with worse outcome in patients with acute stroke.\n We conducted a prospective, randomized, multicenter, 3-arm trial (tight control [target 70 to 110 mg/dL], loose control [target 70 to 200 mg/dL], and control usual care [70 to 300 mg/dL]) to assess the feasibility and safety of 2 insulin infusion protocol targets in patients with acute ischemic stroke. The planned sample was 72 subjects.\n A total of 74 subjects were enrolled. Seventy-two (97%) had data available for the primary analyses and 73 (99%) had 3-month clinical outcome data. Median age was 67 years, median National Institutes of Health Stroke Scale score was 8, median glucose was 163 mg/dL, and median time to randomization was 10.7 hours. Fifty-nine percent of patients were diabetic, 35% received thrombolysis, and 14% of subjects died within 3 months. The loose control and usual care groups had median glucose concentrations of 151 mg/dL. The tight control group had a median glucose concentration of 111 mg/dL. The loose control group spent 90% of the first 24 hours in target and the tight group 44% of time in target. There was only one symptomatic patient with hypoglycemia in the loose control group (4%) and zero in the tight control group. The overall rates of hypoglycemia (<55 mg/dL) were 4% in control, 4% in loose, and 30% in tight. Exploratory efficacy analysis was conducted.\n Insulin infusion for patients with acute ischemic stroke is feasible and safe using the insulin infusion protocol in the Glucose Regulation in Acute Stroke Patients (GRASP) trial. Exploratory efficacy analysis supports further comparative study." ]

[ "12020525", "6611385", "10994153", "8684101", "6384419", "3302093", "15972565", "8656171", "18559367", "7864949", "3668366", "3525736", "8790652" ]

[ "Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial.", "The treatment of acute bronchitis with trimethoprim and sulfamethoxazole.", "Efficacy and tolerability of myrtol standardized in acute bronchitis. A multi-centre, randomised, double-blind, placebo-controlled parallel group clinical trial vs. cefuroxime and ambroxol.", "Effects of antibiotic treatment in the subset of common-cold patients who have bacteria in nasopharyngeal secretions.", "A randomized, controlled trial of doxycycline in the treatment of acute bronchitis.", "A placebo-controlled, double-blind trial of erythromycin in adults with acute bronchitis.", "Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial.", "Effectiveness of erythromycin in the treatment of acute bronchitis.", "Placebo found equivalent to amoxicillin for treatment of acute bronchitis in Nairobi, Kenya: a triple blind, randomised, equivalence trial.", "Albuterol delivered by metered-dose inhaler to treat acute bronchitis.", "Doxycycline in acute bronchitis: a randomized double-blind trial.", "Erythromycin in the treatment of acute bronchitis in a community practice.", "Effects of doxycycline in patients with acute cough and purulent sputum: a double blind placebo controlled trial." ]

[ "The value of azithromycin for treatment of acute bronchitis is unknown, even though this drug is commonly prescribed. We have investigated this question in a randomised, double-blind, controlled trial.\n Adults diagnosed with acute bronchitis, without evidence of underlying lung disease, were randomly assigned azithromycin (n=112) or vitamin C (n=108) for 5 days (total dose for each 1.5 g). All individuals were also given liquid dextromethorphan and albuterol inhaler with a spacer. The primary outcome was improvement in health-related quality of life at 7 days; an important difference was defined as 0.5 or greater. Analysis was by intention to treat.\n The study was stopped by the data-monitoring and safety committee when 220 patients had been recruited. On day 7, the adjusted difference in health-related quality of life was small and not significant (difference 0.03 [95% CI -0.20 to 0.26], p=0.8). 86 (89%) of 97 patients in the azithromycin group and 82 (89%) of 92 in the vitamin C group had returned to their usual activities by day 7 (difference 0.5% [-10% to 9%], p>0.9). There were no differences in the frequency of adverse effects; three patients in the vitamin C group discontinued the study medicine because of perceived adverse effects, compared with none in the azithromycin group. Most patients (81%) reported benefit from the albuterol inhaler.\n Azithromycin is no better than low-dose vitamin C for acute bronchitis. Further studies are needed to identify the best treatment for this disorder.", "Sixty-seven previously healthy patients with acute bronchitis were randomized and treated with either a fixed dose of trimethoprim and sulfamethoxazole or placebo for seven days. All outcomes examined showed a trend favoring the use of antibiotic, with statistically significant differences for cough, night cough, mean temperature, and use of antihistamines or decongestants. Night cough occurred on 84 percent of nights in the control group vs 56 percent in the antibiotic group (P = .003). Cough occurred on 99 percent of days for patients in the control group vs 93 percent of days for patients in the antibiotic group (P = .05). Mean temperature over the seven nights was 37.3 degrees C in the control group vs 36.9 degrees C in the antibiotic group (P = .004). The use of antihistamines and decongestants was reduced from 32 percent of days in the control group to 6 percent of days in the antibiotic group (P = .005). Patients in the antibiotic group worked 73 percent of days vs 55 percent of days for patients in the control group, which was significant when patients were stratified by the appearance of their sputum on Gram stain (P = .006). Smoking history was not found to help predict the response to antibiotic therapy.", "Myrtol standardized (Gelomyrtol forte) is a phytotherapeutic extract (distillate) consisting mainly of three monoterpenes: (+)alpha-pinene, d-limonene and 1,8-cineole.\n This study describes and compares the efficacy, safety and tolerability of a 2-week treatment with myrtol stand. (4 x 300 mg, day 1-14), cefuroxime (CAS 55268-75-2) (2 x 250 mg daily for day 1-6), ambroxol (CAS 18683-91-5) (3 x 30 mg for day 1-3, 2 x 30 mg for days 4-14) and matched placebo in acute bronchitis.\n 676 male and female outpatients, aged > or = 18 years, with acute bronchitis of recent onset (within last 5 days), with an FEV1 > 75% of the normal EGKS-value and without evidence or suspicion of chronic pulmonary disease or any further confounding illness were included in the study.\n Patients were randomly assigned to a 2-week treatment course with either myrtol stand. (N = 170), cefuroxime (N = 171), ambroxol (N = 163) or placebo (N = 172) in a double-blind, placebo-matched, parallel-group fashion. Evaluations were at baseline (visit 1), after 1 and 2 weeks of treatment (visits 2 and 3) and at 2 weeks after conclusion of the treatments (visit 4). CRITERIA: Responder- and non-responder rates (primary), signs (abnormal auscultation), symptoms (daily diary data on nightly cough, coughing fits during the day, sputum consistence and general well-being; visit data on bronchial hyperreactivity and absence/presence of associated symptoms), FEV1, overall efficacy, absence of relapse, safety and tolerability (adverse events, laboratory screens, vital signs and physical examination). Criteria were evaluated for the intention-to-treat data-set (ITT) and the 'efficacy evaluable' sample (EAP), i.e. excluding patients with missing values (incl. discontinued non-responders and drop-outs for other reasons) at the time of assessment.\n The signs and symptoms of acute bronchitis regressed readily in all treatment groups, but regression was slower and less complete in the patients treated with placebo. In patients treated with placebo, the acute bronchitis was considered to have deteriorated to such an extent that discontinuation was indicated ('non-responder') in 36 patients (ITT: 20.9%, 95% CI: 15.1 to 27.8% and EAP: 21.3%, CI: 15.4 to 28.3%) after 1 week (visit 2) and in 19 further patients (ITT: 11.0%, CI: 6.8 to 16.7%; EAP: 14.8%, CI: 9.2 to 22.2%) after 1 further week (visit 3). In contrast, in the group of patients treated with myrtol stand. the non-responder rates at visits 2 and 3 were only 5.3% (ITT, CI: 2.4 to 9.8%; EAP: 5.4%, CI: 2.5 to 10.0%) and 1.2% (ITT, CI: 0.1 to 4.2%; EAP: 1.3%, CI: 0.2 to 4.7%); the responder rates at visit 2 were statistically significantly higher (p < 0.001) for myrtol stand. (ITT: 92.9%, CI: 88.0 to 96.3) compared to placebo (ITT: 77.3%, CI: 70.3 to 83.4), and similar to those for cefuroxime (ITT: 92.4%, CI: 87.4 to 95.9) and ambroxol (ITT: 89.6%, CI: 83.8 to 93.8%). The superiority of the active treatments vs. placebo with little difference among the treatments was confirmed for all further criteria of evaluation. There was no evidence of bronchoconstriction or relapse in any treatment group for the patients continuing treatment (i.e. for those who were not discontinued because of non-response). The treatments were safe and comparably well tolerated.\n Compared to placebo, treatment with myrtol stand. was well tolerated but evidently superior in terms of efficacy, resulting in a more rapid and more complete recovery; although well comparable with the other active treatments, myrtol stand. tended to be superior to cefuroxime and ambroxol for several ancillary criteria. Myrtol stand. is a well-evidenced alternative to antibiotics for acute bronchitis without specified infective agent, without the risk to promote the development of bacterial resistance.", "Upper-respiratory-tract infection is one of the main causes of overuse of antibiotics. We have found previously that bacteria such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae can be isolated from the nasopharyngeal secretions of a substantial proportion of adults with upper-respiratory-tract infections. We have assessed the efficacy of co-amoxiclav in patients with common colds but no clinical signs of sinusitis or other indications for antibiotics.\n Between January, 1992 and March, 1994, 314 patients who presented to our outpatient clinic with common colds were enrolled in the double-blind, placebo-controlled study. They were randomly assigned 5 days' treatment with co-amoxiclav (375 mg three times daily) or identical placebo. Clinical examinations were done at enrolment and on day 5-7 to assess outcome (cured, persistent symptoms, worse symptoms). Seven patients were excluded after randomisation, seven did not have nasopharyngeal aspiration, and 12 did not return for followup assessment.\n Of 300 patients with nasopharyngeal aspirates, 72 had negative bacterial cultures, 167 had cultures positive only for bacteria unrelated to respiratory infections, and 61 had cultures positive for H influenzae, M catarrhalis, or S pneumoniae. At 5-day follow-up of these culture-positive patients, the distribution of outcome was significantly better among co-amoxiclav-treated (n=30) than placebo-treated (n=28) patients (cured 27 vs 4%; persistent symptoms 70 vs 60%; worse symptoms 3 vs 36%; p=0.001). Patients on co-amoxiclav also scored their symptoms significantly lower than patients on placebo (p=0.008). Among culture-negative patients (n=230), the outcome distribution did not differ between the treatment groups (p=0.392).\n The majority of patients with upper-respiratory-tract infection do not benefit from antibiotics and side-effects are frequent. However, for the subgroup whose nasopharyngeal secretions contain H influenzae, M catarrhalis, or S pneumoniae, antibiotics are clinically beneficial.", "Acute bronchitis is a common reason for visits to primary care physicians and a commonly given reason for antibiotic treatment. However, evidence regarding the efficacy of antibiotics for this syndrome is lacking. In a randomized trial, a one-week course of a frequently used antibiotic, doxycycline, was compared with one week of placebo in 74 otherwise healthy adults with acute bronchitis. The doxycycline group fared no better than the placebo group for all 13 outcomes measured, including duration of cough, clinical improvement at one week, return visits for unresolved symptoms, days away from work, and subjective ratings of cough severity, sleep loss, diminished activity and overall well-being. Doxycycline is not beneficial in the treatment of acute bronchitis in otherwise healthy adults.", "Sixty-three otherwise healthy adults with acute productive cough and no clinical evidence of pneumonia were randomized to receive a ten-day course of erythromycin or placebo. Fifty-seven of these patients returned completed symptom diaries or returned for a two-week follow-up visit. Patients treated with erythromycin reported a more rapid improvement in subjective ratings of cold symptoms, general health, sputum production, and a mean symptom score. Fewer patients in the erythromycin group required cough or cold medications or were congested by day 10 (P less than .05). The treatment group was also less likely to have purulent sputum (9 percent vs 36 percent, P less than .05) and abnormal lung examinations (0 percent vs 29 percent, P less than .01) at a two-week follow-up visit. These results support the use of erythromycin in acute bronchitis.", "Acute lower respiratory tract infection is the most common condition treated in primary care. Many physicians still prescribe antibiotics; however, systematic reviews of the use of antibiotics are small and have diverse conclusions.\n To estimate the effectiveness of 3 prescribing strategies and an information leaflet for acute lower respiratory tract infection.\n A randomized controlled trial conducted from August 18, 1998, to July 30, 2003, of 807 patients presenting in a primary care setting with acute uncomplicated lower respiratory tract infection. Patients were assigned to 1 of 6 groups by a factorial design: leaflet or no leaflet and 1 of 3 antibiotic groups (immediate antibiotics, no offer of antibiotics, and delayed antibiotics).\n Three strategies, immediate antibiotics (n = 262), a delayed antibiotic prescription (n = 272), and no offer of antibiotics (n = 273), were prescribed. Approximately half of each group received an information leaflet (129 for immediate antibiotics, 136 for delayed antibiotic prescription, and 140 for no antibiotics).\n Symptom duration and severity.\n A total of 562 patients (70%) returned complete diaries and 78 (10%) provided information about both symptom duration and severity. Cough rated at least \"a slight problem\" lasted a mean of 11.7 days (25% of patients had a cough lasting > or =17 days). An information leaflet had no effect on the main outcomes. Compared with no offer of antibiotics, other strategies did not alter cough duration (delayed, 0.75 days; 95% confidence intervals [CI], -0.37 to 1.88; immediate, 0.11 days; 95% CI, -1.01 to 1.24) or other primary outcomes. Compared with the immediate antibiotic group, slightly fewer patients in the delayed and control groups used antibiotics (96%, 20%, and 16%, respectively; P<.001), fewer patients were \"very satisfied\" (86%, 77%, and 72%, respectively; P = .005), and fewer patients believed in the effectiveness of antibiotics (75%, 40%, and 47%, respectively; P<.001). There were lower reattendances within a month with antibiotics (mean attendances for no antibiotics, 0.19; delayed, 0.12; and immediate, 0.11; P = .04) and higher attendance with a leaflet (mean attendances for no leaflet, 0.11; and leaflet, 0.17; P = .02).\n No offer or a delayed offer of antibiotics for acute uncomplicated lower respiratory tract infection is acceptable, associated with little difference in symptom resolution, and is likely to considerably reduce antibiotic use and beliefs in the effectiveness of antibiotics.", "Clinical trials have not shown a consistent benefit of treating bronchitis with antibiotics. Many physicians, however, treat acute bronchitis with antibiotics because of the possibility of Mycoplasma pneumoniae or other pathogens. The objectives of this study were to determine the effectiveness of erythromycin treatment in patients with acute bronchitis and to determine whether a newly developed rapid M pneumoniae antibody test is useful in predicting which patients will respond to therapy.\n We conducted a randomized, double-blind, placebo-controlled clinical trial at three primary care centers in North Carolina. A convenience sample of 140 patients presenting with acute bronchitis were tested for M pneumoniae, 91 of whom were treated with either erythromycin 250 mg four times daily for 10 days or an identical-appearing placebo.\n Patients treated with erythromycin missed an average of only 0.81 +/- 1.1 days of work compared with 2.16 +/- 3.2 days for placebo-treated patients (P < .02). There were no significant differences in cough, use of cough medicine, general feeling of well-being, or chest congestion between the erythromycin and placebo groups. Twenty-five percent of the patients tested positive for M pneumoniae. There were no differences in response to erythromycin based on whether the patient had a positive test for M pneumoniae.\n Erythromycin is effective in significantly reducing lost time from work, but it is not effective in reducing cough or other symptoms in patients with acute bronchitis, regardless of the outcome of the M pneumoniae antibody test.", "Antibiotic treatment is not recommended for acute bronchitis in immunocompetent patients in industrialised countries. Whether these recommendations are relevant to the developing world and to immunocompromised patients is unknown. Design,\n Randomised, triple blind, placebo controlled equivalence trial of amoxicillin compared with placebo in 660 adults presenting to two outpatient clinics in Nairobi, Kenya, with acute bronchitis but without evidence of chronic lung disease.\n The primary study end point was clinical cure, as defined by a >or=75% reduction in a validated Acute Bronchitis Severity Score by 14 days; analysis was by intention to treat with equivalence defined as <or=8% difference between study arms.\n Clinical cure rates in the amoxicillin and placebo arms were 81.7% and 84.0%, respectively (difference 2.3%, 95% CI -8.6% to 4.0%). Of 131 HIV infected subjects (19.8%), cure rates for those randomised to amoxicillin (77.2%) and placebo (83.8%) differed by 6.6% (95% CI -21.7% to 8.6%). Among HIV uninfected subjects, the difference in cure rates was 1.6% (95% CI -8.5% to 5.3%). Potential drug side effects were similar in the two arms. No subjects required hospitalisation or died.\n Antibiotic treatment of acute bronchitis is unhelpful, even in populations with a high prevalence of HIV infection.", "Previous research has suggested that cough associated with acute bronchitis is more likely to subside within 7 days when treated with albuterol than with an antibiotic. This study examines the effectiveness of aerosolized albuterol for the treatment of acute bronchitis in patients treated with erythromycin or placebo.\n A double-blind, randomized placebo-controlled trial of albuterol delivered by metered-dose inhaler (MDI) was conducted in a primary care setting with healthy adult patients who presented with a productive cough of fewer than 30 days' duration. In addition to randomization for albuterol, patients were also randomized to receive erythromycin or placebo. Outcomes were assessed at follow-up after 7 days.\n Patients treated with albuterol MDI were less likely to be coughing after 7 days of treatment than were patients using a placebo inhaler (61% still coughing vs 91%, P = .02). When analysis was stratified by cigarette smoking status and the use of erythromycin, the differences observed between albuterol MDI patients and controls persisted.\n Albuterol appears to reduce the likelihood that patients with acute bronchitis will be coughing after 7 days following initiation of treatment. This effect appears to be independent of cigarette smoking or the concomitant use of antibiotics.", "nan", "To assess the efficacy of erythromycin in treating acute bronchitis, 52 adults were enrolled in a randomized trial comparing a one-week course of erythromycin with placebo. Among smokers, no difference in outcome was noted. Among nonsmokers, trends favored more rapid resolution of key symptoms in the erythromycin group, but these trends did not generally achieve statistical significance. These results suggest a trial with a larger sample size.", "Acute cough with purulent sputum is a common complaint presented to general practitioners.\n A randomized, double blind, placebo controlled clinical trial was undertaken to determine the efficacy of doxycycline in persons aged 18 years and over presenting to 22 general practices in the Netherlands with acute cough and purulent sputum.\n Patients were excluded if they were pregnant, had an allergy or intolerance to tetracyclines, had severe dyspnoea and fine crackles on auscultation, purulent rhinitis together with maxillary tenderness, chronic airways disease, or had taken antibiotics in the previous two weeks. Patients entered in to the study were given oral doxycycline for 10 days, 200 mg on the first day, followed by 100 mg on the next nine days, or placebo.\n Duration of frequent daytime cough after entry was a mean of 1.5 days shorter in the group of 71 patients receiving doxycycline than in the group of 69 patients on placebo (4.7 days versus 6.2 days, respectively). In patients aged 55 years and over the mean duration of frequent day-time cough after entry was 4.1 days shorter in the group taking doxycycline than in the placebo group. Patients with a very frequent cough and who also felt ill at entry regained their normal daily activities 2.1 days earlier when using doxycycline than the control group.\n Doxycycline has small beneficial effects in patients with acute cough and purulent sputum. These beneficial effects are more prominent, and probably clinically relevant, in patients aged 55 years and over and in patients who cough very frequently and who also feel ill." ]

[ "3300178", "4899454", "13492604" ]

[ "Trimethoprim prophylaxis of acute exacerbations in chronic obstructive pulmonary diseases.", "Five-year winter chemoprophylaxis for chronic bronchitis.", "Long-continued treatment with tetracycline and prednisolone in chronic bronchitis; a controlled trial." ]

[ "A double-blind randomized trial was carried out to study the efficacy and tolerance of trimethoprim with a daily single dose of 300 mg in long-term prophylaxis of acute exacerbations of chronic obstructive pulmonary diseases (COPD). The patients, 13 in the trimethoprim group and 11 in the placebo group, were followed up at fixed intervals and checked for respiratory functions and haematological parameters for six months. The number of exacerbations were significantly lower than during the previous winter in both groups: 0.6 compared to 3.8 in the trimethoprim group, and 0.6 to 3.0 in the placebo group. Tolerance of trimethoprim was good and did not differ from that of placebo. The necessity of double-blind trials in evaluating the prophylactic value of antibiotics in COPD is emphasized, since the exacerbations are also dependent on many unknown factors. There were no statistically significant differences in blood counts of folate levels.", "Seventy-nine patients with chronic bronchitis were randomly allotted to four treatment regimens-placebo throughout the winter months for five years; tetracycline for the first two winters and placebo for the next three; placebo for the first two winters and tetracycline for the next three; and tetracycline for five winters. In addition all groups recevied a five-day course of tetracycline for any acute exacerbation. There was a significant reduction in the number of exacerbations among the more susceptible patients-that is, those who suffered more than one exacerbation each winter. Though the average decline in F.E.V.(1) over the five-year period was less in the treated groups this was not statistically significant. There was no significant difference between the groups in respect of lung volumes, diffusing capacity, and blood gases.", "nan" ]

[ "21550483", "19277796", "19779986", "7749676", "16736333" ]

[ "Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial.", "Conservative management of acute appendicitis.", "Comparison of operative and non operative management of acute appendicitis.", "Randomized controlled trial of appendicectomy versus antibiotic therapy for acute appendicitis.", "Appendectomy versus antibiotic treatment in acute appendicitis. a prospective multicenter randomized controlled trial." ]

[ "Researchers have suggested that antibiotics could cure acute appendicitis. We assessed the efficacy of amoxicillin plus clavulanic acid by comparison with emergency appendicectomy for treatment of patients with uncomplicated acute appendicitis.\n In this open-label, non-inferiority, randomised trial, adult patients (aged 18-68 years) with uncomplicated acute appendicitis, as assessed by CT scan, were enrolled at six university hospitals in France. A computer-generated randomisation sequence was used to allocate patients randomly in a 1:1 ratio to receive amoxicillin plus clavulanic acid (3 g per day) for 8-15 days or emergency appendicectomy. The primary endpoint was occurrence of postintervention peritonitis within 30 days of treatment initiation. Non-inferiority was shown if the upper limit of the two-sided 95% CI for the difference in rates was lower than 10 percentage points. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT00135603.\n Of 243 patients randomised, 123 were allocated to the antibiotic group and 120 to the appendicectomy group. Four were excluded from analysis because of early dropout before receiving the intervention, leaving 239 (antibiotic group, 120; appendicectomy group, 119) patients for intention-to-treat analysis. 30-day postintervention peritonitis was significantly more frequent in the antibiotic group (8%, n=9) than in the appendicectomy group (2%, n=2; treatment difference 5·8; 95% CI 0·3-12·1). In the appendicectomy group, despite CT-scan assessment, 21 (18%) of 119 patients were unexpectedly identified at surgery to have complicated appendicitis with peritonitis. In the antibiotic group, 14 (12% [7·1-18·6]) of 120 underwent an appendicectomy during the first 30 days and 30 (29% [21·4-38·9]) of 102 underwent appendicectomy between 1 month and 1 year, 26 of whom had acute appendicitis (recurrence rate 26%; 18·0-34·7).\n Amoxicillin plus clavulanic acid was not non-inferior to emergency appendicectomy for treatment of acute appendicitis. Identification of predictive markers on CT scans might enable improved targeting of antibiotic treatment.\n French Ministry of Health, Programme Hospitalier de Recherche Clinique 2002.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "The acute appendicitis is the most common abdominal emergency, and the primary treatment has been appendicectomy. Antibiotics are started preoperatively and continued postoperatively as needed.\n This prospective study was carried out at Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India to determine the role of antibiotics as the only treatment in acute appendicitis and the analgesic consumption needed. Total of 80 patients were included in the study with a duration of abdominal pain less than 72 h. Out of 80 patients, 40 patients received antibiotics intravenously for 2 days followed by oral treatment for 7 days, while another 40 patients considered as controls were randomized to surgery.\n Patients managed conservatively were discharged within 3 days except for two--patients who required surgery after 12 and 24 h, respectively, because of peritonitis due to perforated appendicitis. Four patients were readmitted within 1 year as a result of recurrent appendicitis and had to undergo surgery when appendicitis was confirmed. The diagnostic accuracy within the operated group was 90%. Two patients had perforated appendicitis at operation.\n Our conclusion is that antibiotic treatment in the patients with acute appendicitis is quite effective, and these patients may not need surgery. The patients managed conservatively with antibiotics alone experience less pain and require less analgesia but have high recurrent rate.", "In this prospective study, operative and nonoperative management of acute appendicitis were evaluated regarding their safety and cost effectiveness.\n Two hundred ninety patients presenting to our Emergency Department between March 2005 and March 2006 with acute appendicitis were included in this prospective study. Nonoperative medical therapy was performed in 107 patients (Group 1), and 183 patients were treated surgically (Group 2). Routine follow-up controls were done on the 10th day, at the 3rd and 6th months and at the first year after discharge in Group 1. Both groups were compared regarding age, gender, mean hospital stay, modified Alvarado score, morbidity, mortality, and cost effectiveness.\n The male/female ratio of Groups 1 and 2 were 65/42 (mean age: 30.98+/-1.30) and 125/58 (mean age: 26.25+/-0.79), respectively. In Group 1, 19 patients were operated. Operation indications were resistance to therapy, patient's request, and operation in another hospital. Although the mean hospital stay of Group 1 was statistically significantly longer than Group 2, the mean cost of the therapy was $559 in Group 2 and $433 in Group 1. Morbidity rates were similar, with no mortality in either group.\n With its high success rate and cost effectiveness, medical treatment seems to be a good alternative to the gold standard therapy of surgery in management of acute appendicitis.", "In a prospective controlled study the effect of antibiotics as the only treatment in acute appendicitis was evaluated. Of 40 patients admitted with a duration of abdominal pain of less than 72 h, 20 received antibiotics intravenously for 2 days followed by oral treatment for 8 days and 20 considered as controls were randomized to surgery. All patients treated conservatively were discharged within 2 days, except one who required surgery after 12 h because of peritonitis secondary to perforated appendicitis. Seven patients were readmitted within 1 year as a result of recurrent appendicitis and underwent surgery, when appendicitis was confirmed. The diagnostic accuracy within the operated group was 85 per cent. One patient had perforated appendicitis at operation. Antibiotic treatment in patients with acute appendicitis was as effective as surgery. The patients had less pain and required less analgesia, but the recurrence rate was high.", "Appendectomy has been the treatment for acute appendicitis for over 120 years. Antibiotic treatment has occasionally been used in small uncontrolled studies, instead of operation, but this alternative has never before been tried in a multicenter randomized trial.\n Male patients, 18-50 years of age, admitted to six different hospitals in Sweden between 1996 and 1999 were enrolled in the study. No women were enrolled by decision of the local ethics committee. If appendectomy was planned, patients were asked to participate, and those who agreed were randomized either to surgery or to antibiotic therapy. Patients randomized to surgery were operated on with open surgery or laparoscopically. Those randomized to antibiotic therapy were treated intravenously for 2 days, followed by oral treatment for 10 days. If symptoms did not resolve within 24 hours, an appendectomy was performed. Participants were monitored at the end of 1 week, 6 weeks, and 1 year.\n During the study period 252 men participated, 124 in the surgery group and 128 in the antibiotic group. The frequency of appendicitis was 97% in the surgery group and 5% had a perforated appendix. The complication rate was 14% in the surgery group. In the antibiotic group 86% improved without surgery; 18 patients were operated on within 24 hours, and the diagnosis of acute appendicitis was confirmed in all but one patient, and he was suffering from terminal ileitis. There were seven patients (5%) with a perforated appendix in this group. The rate of recurrence of symptoms of appendicitis among the 111 patients treated with antibiotics was 14% during the 1-year follow-up.\n Acute non-perforated appendicitis can be treated successfully with antibiotics. However, there is a risk of recurrence in cases of acute appendicitis, and this risk should be compared with the risk of complications after appendectomy." ]

[ "10464004", "11787934", "9819872", "9297265" ]

[ "24-hour ambulatory blood pressure monitoring: a comparison between transdermal glyceryl-trinitrate and oral nifedipine.", "Re: glyceryl trinitrate (GTN) patches are unsuitable in hypertensive pregnancy.", "The efficacy and fetal-maternal cardiovascular effects of transdermal glyceryl trinitrate in the prophylaxis of pre-eclampsia and its complications: a randomized double-blind placebo-controlled trial.", "[Nitric oxide: its role in the development of pregnancy complications and in their prevention in women with hypertension and chronic glomerulonephritis]." ]

[ "The objective of the present study is to compare the effectiveness of transdermal glyceryl-trinitrate versus oral nifedipine in lowering blood pressure in patients affected by pregnancy-induced hypertension (PIH). Thirty-six consecutive pregnant women have been evaluated at different gestational ages after the diagnosis of PIH or preeclampsia (PE). After a 24-h ambulatory blood pressure monitoring, patients were allocated to three groups: those receiving oral nifedipine and those receiving transdermal glyceryl-trinitrate in a continuous (24 h/day) or intermittent (16 h/day) administration. A second blood pressure monitoring was performed after 2 weeks of treatment. Systolic and diastolic blood pressure were compared by using the Cosinor method looking at mesor, amplitude, and acrophase. Baseline systolic and diastolic blood pressure was similar among the three groups. Neither the transdermal glyceryl-trinitrate administered for 24 or 16 h nor oral nifedipine affected systolic and diastolic blood pressure. Analysis of variance showed that the posttreatment values were similar among the groups. Further studies are needed to verify the possible use of transdermal glyceryl-trinitrate as an antihypertensive drug during pregnancy.", "nan", "Pre-eclampsia continues to be a major cause of maternal and perinatal mortality. A disorder of the nitric oxide system is implicated in the pathogenesis of this condition and preliminary studies have suggested a possible therapeutic role for nitric oxide donors in women with established pre-eclampsia. The aim of this study was to determine whether pre-eclampsia and its complications could be prevented by the long-term use of nitric oxide donors in a group of women identified to be at risk on the basis of abnormal uterine artery Doppler measurements.\n We enrolled 40 healthy normotensive women at high risk of pre-eclampsia selected on the basis of abnormal uterine artery Doppler waveforms at 24-26 weeks of gestation. Women were randomly allocated to receive transdermal glyceryl trinitrate 5 mg-patches or equivalent placebo patches in a double-blind randomized study. The primary outcome measures were pre-eclampsia, fetal growth restriction, preterm delivery or small for gestational age/fetal growth restriction rates. Patches were worn daily from recruitment for 10 weeks or until delivery.\n The primary outcomes were not significantly different in the placebo compared to the glyceryl trinitrate group. However, survival analysis of adverse events with gestation in both groups showed a significantly reduced risk of an adverse event in the glyceryl trinitrate group (p = 0.004), equating to a 73% reduction in hazard. There was no difference in maternal systolic and diastolic blood pressure, mean uterine artery resistance index and fetal umbilical and middle cerebral artery pulsatility indices between the groups.\n Low-dose prophylactic transdermal glyceryl trinitrate commenced late in the second trimester did not reduce the incidence of pre-eclampsia, preterm delivery or fetal growth restriction, but may increase the likelihood of a complication-free pregnancy. Transdermal glyceryl trinitrate (5 mg/day) did not affect maternal cardiovascular, uterine artery or fetal arterial Doppler parameters.", "The activity of NO-synthase and formation of NO (EDRF) were assessed by an increase in the activity of NO-dependent hyanilate cyclase in response to L-arginine in vitro in platelets of 61 pregnant females (39, 8 14 with essential hypertension, preeclampsia and healthy controls, respectively) and in 9 hypertensive nonpregnant females. Compared to healthy pregnant females, EDRF synthesis activity was inhibited in hypertensive gravidas but enhanced in preeclampsia patients. Effectiveness of exogenic donator NO (transdermal nitroglycerine, Nitroderm NNS 5) was studied in a randomised trial of 76 gravidas with essential hypertension (EH), EH and chronic glomerulonephritis (GN). 39 of them were given transdermal nitroglycerine, 37 received acetylsalicilic acid and curantil. The number of treatment failures was the same in both groups. The conclusion is made that nitro compounds are adequate for use in EH and chronic GN gravidas." ]

[ "5409834", "9185396", "4955380", "6241559" ]

[ "Lactation and genital involution effects of a new low-dose oral contraceptive on breast-feeding mothers and their infants.", "Randomised clinical trial to determine optimum initiation time of norgestrel-progestin only contraception in Eldoret Teaching Hospital, Kenya.", "Post partum ovulation: inhibition and milk yield.", "Effects of hormonal contraceptives on milk volume and infant growth. WHO Special Programme of Research, Development and Research Training in Human Reproduction Task force on oral contraceptives." ]

[ "nan", "In a randomised controlled trial to determine the optimum time of initiation of Ovrette, a progestin only oral contraceptive among postpartum women, who fully or nearly fully breast-fed their infants in the first six months, no difference was found between group 1 (initiating at six weeks postpartum) and group 2 (initiating the pill at return of menses or 6 months postpartum). There were no pregnancies in either group during the 18 month follow-up. There were no significant differences in the continuation rates between the two group.", "nan", "WHO conducted a three-centre study in Hungary and Thailand to evaluate the effects of hormonal contraception on lactation and infant growth. Women choosing oral contraceptives were randomly assigned to a combined oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel (N = 86) or a progestin-only preparation containing 75 micrograms dl-norgestrel (N = 85). Identical packaging and treatment schedules allowed double-blind observation. One-hundred-and-eleven women using no contraception or non-hormonal methods acted as controls. In the two Thai centres 59 women using depot-medroxyprogesterone acetate formed an additional comparison group. All subjects were healthy women with normal deliveries, whose infants had normal birth weights and satisfactory growth in the neonatal period. Breast milk volume was determined by pump expression using standardized procedures. Information was obtained on nursing frequency and supplementation, infant growth and morbidity. Pretreatment observations at 6 weeks post-partum were used as a baseline, and subjects were followed-up at 9, 12, 16, 20 and 24 weeks post-partum. Women using combined oral contraceptives had a decline in milk volume within 6 weeks of initiating treatment, whereas no significant decrease was observed in the other treatment groups. After 18 weeks of treatment, combined oral contraceptive users experienced a 41.9% decline in milk volume, compared to 12.0% with progestin-only minipills and 6.1% in the non-hormonal controls. The prevalence of complementary feeding and withdrawals due to inadequate milk supply were comparable in the four treatment groups. However, data were not available on the daily amounts of complementary feeds. There were no significant differences in growth of infants between treatment groups. Thus, women may have compensated for declines in milk volume by more supplementary feeding or by more prolonged and intense suckling episodes. We conclude that 30 micrograms estrogen-containing combined oral contraceptives impair milk secretion, but in the selected healthy group of mothers and children studied with the prevailing level of supplementary feeding, this did not adversely affect infant growth." ]

[ "11073017", "9887161" ]

[ "Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group.", "Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group." ]

[ "Some epidemiological studies have suggested that high dietary intake of calcium and fibre reduces colorectal carcinogenesis. Available data are not sufficient to serve as a basis for firm dietary advice. We undertook a multicentre randomised trial to test the effect of diet supplementation with calcium and fibre on adenoma recurrence.\n We randomly assigned 665 patients with a history of colorectal adenomas to three treatment groups, in a parallel design: calcium gluconolactate and carbonate (2 g elemental calcium daily), fibre (3.5 g ispaghula husk), or placebo. Participants had colonoscopy after 3 years of follow-up. The primary endpoint was adenoma recurrence. Analyses were by intention to treat.\n 23 patients died, 15 were lost to follow-up, 45 refused repeat colonoscopy, and five developed severe contraindications to colonoscopy. Among the 552 participants who completed the follow-up examination, 94 stopped treatment early. At least one adenoma developed in 28 (15.9%) of 176 patients in the calcium group, 58 (29.3%) of 198 in the fibre group, and 36 (20.2%) of 178 in the placebo group. The adjusted odds ratio for recurrence was 0.66 (95% CI 0.38-1.17; p=0.16) for calcium treatment and 1.67 (1.01-2.76, p=0.042) for the fibre treatment. The odds ratio associated with the fibre treatment was significantly higher in participants with baseline dietary calcium intake above the median than in those with intake below the median (interaction test, p=0.028)\n Supplementation with fibre as ispaghula husk may have adverse effects on colorectal adenoma recurrence, especially in patients with high dietary calcium intake. Calcium supplementation was associated with a modest but not significant reduction in the risk of adenoma recurrence.", "Laboratory, clinical, and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas. We conducted a randomized, double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas. We randomly assigned 930 subjects (mean age, 61 years; 72 percent men) with a recent history of colorectal adenomas to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas were adjusted for age, sex, lifetime number of adenomas before the study, clinical center, and length of the surveillance period.\n The subjects in the calcium group had a lower risk of recurrent adenomas. Among the 913 subjects who underwent at least one study colonoscopy, the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 (95 percent confidence interval, 0.74 to 0.98; P=0.03). The main analysis was based on the 832 subjects (409 in the calcium group and 423 in the placebo group) who completed both follow-up examinations. At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group (31 percent) and 159 subjects in the placebo group (38 percent); the adjusted risk ratio was 0.81 (95 percent confidence interval, 0.67 to 0.99; P=0.04). The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 (95 percent confidence interval, 0.60 to 0.96; P=0.02). The effect of calcium was independent of initial dietary fat and calcium intake.\n Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas." ]

[ "7915348", "10201714", "11568372" ]

[ "Placebo-controlled trial of midazolam sedation in mechanically ventilated newborn babies.", "Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates.", "Midazolam sedation in mechanically ventilated newborns: a double blind randomized placebo controlled trial." ]

[ "Although midazolam is used for sedation of mechanically ventilated newborn babies, this treatment has not been evaluated in a randomised trial. We have done a prospective placebo-controlled study of the effects of midazolam on haemodynamic variables and sedation as judged by a five-item behaviour score. 46 newborn babies on mechanical ventilation for respiratory distress syndrome were randomly assigned to receive midazolam (n = 24) or placebo (n = 22) as a continuous infusion. Doses of midazolam were calculated to obtain plasma concentrations between 200 and 1000 ng/mL within 24 h of starting treatment and to maintain these values throughout the study. Haemodynamic and ventilatory variables were noted every hour, as were complications and possible side-effects of treatment. Mean (SD) duration of inclusion was 78.7 (30.9) h. 1 patient in the treatment group and 7 in the placebo group were withdrawn because of inadequate sedation (p < 0.05). Midazolam gave a significantly better sedative effect than placebo, as estimated by the behaviour score (p < 0.05). Heart rate and blood pressure were reduced by treatment but remained within the normal range for gestational age and there was no effect on ventilatory indices. The incidence of complications was similar in the two groups. No midazolam-related side-effects were noted. Continuous infusion of midazolam at doses adapted to gestational age induces effective sedation in newborn babies on mechanical ventilation, with positive effects on haemodynamic variables. The course of the respiratory distress syndrome was not influenced by this treatment. Midazolam was given over only a few days and the limited effects on heart rate and blood pressure that we report should not encourage long-term administration.", "Preterm neonates are exposed to multiple painful procedures after birth and exhibit acute physiological responses to pain. Occurrence of early intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of pain and stress in the multifactorial causation of severe intraventricular hemorrhage and periventricular leukomalacia. We proposed that such neurologic outcomes in preterm neonates who require ventilatory support may be reduced by morphine analgesia or midazolam sedation compared with a placebo.\n To define the incidence of clinical outcomes in the target study population, to estimate the effect size and adverse effects associated with analgesia and sedation, and to calculate the sample size for a definitive test of this hypothesis.\n Sixty-seven preterm neonates were randomized in a pilot clinical trial from 9 centers. Neonates of 24 to 32 weeks gestation were eligible if they had been intubated and required ventilatory support for less than 8 hours and if they were enrolled within 72 hours after birth. Exclusion criteria included major congenital anomalies, severe intrapartum asphyxia, and participation in other research studies. Severity of illness was assessed by the Clinical Risk Index for Babies, and neonates were randomized to receive continuous infusions of morphine sulfate, midazolam hydrochloride, or 10% dextrose (placebo). Masked study medications were continued as long as clinically necessary, then weaned and stopped according to predefined criteria. Levels of sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile scores) were measured before, during, and 12 hours after discontinuation of drug infusion. Cranial ultrasound examinations were performed as part of routine practice, and poor neurologic outcomes were defined as neonatal death, severe intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia.\n No significant differences occurred in the demographic, clinical, and socioeconomic variables related to mothers and neonates in the 3 groups or in the severity of illness at birth as measured by Clinical Risk Index for Babies scores. Two neonates in the placebo group and 1 neonate in the midazolam group died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in the morphine group (likelihood ratio chi2 = 7.04, P = .03). Secondary clinical outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were similar in the 3 groups. Responses elicited by endotracheal tube suction (Premature Infant Pain Profile scores) were significantly reduced during the morphine (P<.001) and midazolam (P = .002) infusions compared with the placebo group.\n This pilot trial suggests that preemptive analgesia given by continuous low-dose morphine infusion may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Limitations in the sample size of this pilot study suggest that these results should be confirmed in a large multicenter randomized trial.", "To determine efficacy of midazolam as a sedative in mechanically ventilated newborns.\n Double blind randomized placebo controlled trial.\n Neonatal Unit of Tertiary Hospital.\n Sedation over 48 h of observation.\n Neonates with birth weight less than 2000 g who were mechanically ventilated within 7 days of life were randomly assigned to midazolam and placebo group. Midazolam and placebo were administered as bolus (0.2 mg/kg) followed by continuous infusion (0.06 mg/kg/h). Both groups received morphine infusion (10 microg/kg/h). Sedation score was noted at 6 hourly intervals for 48 hours. Hemodynamic variables, ventilatory variables, complications and side effects of treatments were also recorded.\n Thirty-three neonates were enrolled (17 in midazolam, 16 in placebo group). The groups were comparable for birth weights and gestation. The midazolam group had significantly better sedation from 18-24 hours after enrollment compared to placebo group. At 48 h there were no significant differences in proportion of infants with adequate sedation between midazolam and placebo group. The two groups were comparable with respect to heart rate, perfusion, ventilatory indices and blood gas parameters. None of the infants were noted to have hypotension on loading with midazolam or placebo. Seizures were noted in 2 neonates in placebo group 24 hours after enrollment (insignificant statistically).\n Sedation provided by continuous infusion of midazolam and morphine appears to be comparable to morphine alone in newborn babies on mechanical ventilation, with no significant adverse effects. The course of mechanical ventilation is not influenced by use of midazolam." ]

[ "19255407", "16510745", "16510744" ]

[ "GLANCE: results of a phase 2, randomized, double-blind, placebo-controlled study.", "Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.", "A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis." ]

[ "To evaluate the safety and tolerability of natalizumab when added to glatiramer acetate (GA) in patients with relapsing multiple sclerosis. The primary outcome assessed whether this combination would increase the rate of development of new active lesions on cranial MRI scans vs GA alone.\n This phase 2, randomized, double-blind, placebo-controlled study included patients aged 19 to 55 years who were treated with GA for at least 1 year before randomization and experienced at least one relapse during the previous year. Patients received IV natalizumab 300 mg (n = 55) or placebo (n = 55) once every 4 weeks plus GA 20 mg subcutaneously once daily for < or = 20 weeks.\n The mean rate of development of new active lesions was 0.03 with combination therapy vs 0.11 with GA alone (p = 0.031). Combination therapy resulted in lower mean numbers of new gadolinium-enhancing lesions (0.6 vs 2.3 for GA alone, p = 0.020) and new/newly enlarging T2-hyperintense lesions (0.5 vs 1.3, p = 0.029). The incidence of infection and infusion reactions was similar in both groups; no hypersensitivity reactions were observed. One serious adverse event occurred with combination therapy (elective hip surgery). With the exception of an increase in anti-natalizumab antibodies with combination therapy, laboratory data were consistent with previous clinical studies of natalizumab alone.\n The combination of natalizumab and glatiramer acetate seemed safe and well tolerated during 6 months of therapy.", "Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies.\n We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years.\n Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P=0.02). Kaplan-Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P<0.001) and with fewer new or enlarging lesions on T(2)-weighted magnetic resonance imaging (0.9 vs. 5.4, P<0.001). Adverse events associated with combination therapy were anxiety, pharyngitis, sinus congestion, and peripheral edema. Two cases of progressive multifocal leukoencephalopathy, one of which was fatal, were diagnosed in natalizumab-treated patients.\n Natalizumab added to interferon beta-1a was significantly more effective than interferon beta-1a alone in patients with relapsing multiple sclerosis. Additional research is needed to elucidate the benefits and risks of this combination treatment. (ClinicalTrials.gov number, NCT00030966.).\n Copyright 2006 Massachusetts Medical Society.", "Natalizumab is the first alpha4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis.\n Of a total of 942 patients, 627 were randomly assigned to receive natalizumab (at a dose of 300 mg) and 315 to receive placebo by intravenous infusion every four weeks for more than two years. The primary end points were the rate of clinical relapse at one year and the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale, at two years.\n Natalizumab reduced the risk of sustained progression of disability by 42 percent over two years (hazard ratio, 0.58; 95 percent confidence interval, 0.43 to 0.77; P<0.001). The cumulative probability of progression (on the basis of Kaplan-Meier analysis) was 17 percent in the natalizumab group and 29 percent in the placebo group. Natalizumab reduced the rate of clinical relapse at one year by 68 percent (P<0.001) and led to an 83 percent reduction in the accumulation of new or enlarging hyperintense lesions, as detected by T2-weighted magnetic resonance imaging (MRI), over two years (mean numbers of lesions, 1.9 with natalizumab and 11.0 with placebo; P<0.001). There were 92 percent fewer lesions (as detected by gadolinium-enhanced MRI) in the natalizumab group than in the placebo group at both one and two years (P<0.001). The adverse events that were significantly more frequent in the natalizumab group than in the placebo group were fatigue (27 percent vs. 21 percent, P=0.048) and allergic reaction (9 percent vs. 4 percent, P=0.012). Hypersensitivity reactions of any kind occurred in 25 patients receiving natalizumab (4 percent), and serious hypersensitivity reactions occurred in 8 patients (1 percent).\n Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing multiple sclerosis. Adhesion-molecule inhibitors hold promise as an effective treatment for relapsing multiple sclerosis. (ClinicalTrials.gov number, NCT00027300.).\n Copyright 2006 Massachusetts Medical Society." ]

[ "6788319", "2865326", "16442481", "3780329" ]

[ "Drug treatment of breathlessness: contrasting effects of diazepam and promethazine in pink puffers.", "Effects of clorazepate on breathlessness and exercise tolerance in patients with chronic airflow obstruction.", "Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer.", "Effect of alprazolam on exercise and dyspnea in patients with chronic obstructive pulmonary disease." ]

[ "Fifteen out of 18 \"pink and puffing\" patients completed a double-blind, placebo-controlled cross-over trial of diazepam and promethazine for breathlessness and reduced exercise tolerance. Dosages were 25 mg and 125 mg daily, respectively, and each course lasted two weeks. Patients with psychiatric or other major medical histories were excluded. Of the three patients who did not complete the trial, one died during an exacerbation of breathlessness while taking diazepam, one was withdrawn because of mild hypercapnia while taking placebo, and one suffered intolerable drowsiness while taking diazepam. Of the remaining 15 patients, six needed a reduction in dosage because of drowsiness: one of these was taking promethazine and five diazepam. Diazepam had no effect on breathlessness and noticeably reduced exercise tolerance. Promethazine reduced breathlessness and improved exercise tolerance without altering lung function. From these results diazepam is contraindicated for breathlessness and reduced exercise tolerance in fixed airways obstruction, but promethazine may be beneficial.", "Five patients with severe chronic lung disease were given placebo or 7.5 mg of clorazepate, a benzodiazepine, at bedtime for two weeks using a double-blind cross-over study design. Exercise tolerance, arterial blood gases, pulmonary function tests, self-rated breathlessness, and self-administered depression and anxiety scores were similar during drug treatment, placebo treatment, and washout periods. Higher doses of clorazepate were not tolerated by three of five patients. Nonanxious patients with chronic lung disease seem not to benefit subjectively or objectively from a low-dose benzodiazepine regimen.", "The mainstay of dyspnea palliation remains altering its central perception. Morphine is the main drug and anxiolytics have a less established role. This trial assessed the role of midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in terminally ill cancer patients. One hundred and one patients with severe dyspnea were randomized to receive around-the-clock morphine (2.5 mg every 4 hours for opioid-naïve patients or a 25% increment over the daily dose for those receiving baseline opioids) with midazolam rescue doses (5 mg) in case of breakthrough dyspnea (BD) (Group Mo); around-the-clock midazolam (5 mg every 4 hours) with morphine rescues (2.5 mg) in case of BD (Group Mi); or around-the-clock morphine (2.5 mg every 4 hours for opioid-naïve patients or a 25% increment over the daily dose for those receiving baseline opioids) plus midazolam (5 mg every 4 hours) with morphine rescue doses (2.5 mg) in case of BD (Group MM). All drugs were given subcutaneously in a single-blinded way. Thirty-five patients were entered in Group Mo, 33 entered in Mi, and 33 entered in MM. At 24 hours, patients who experienced dyspnea relief were 69%, 46%, and 92% in the Mo, Mi, and MM groups, respectively (P = 0.0004 and P = 0.03 for MM vs. Mi and MM vs. Mo, respectively). At 48 hours, those with no dyspnea relief (no controlled dyspnea) were 12.5%, 26%, and 4% for the Mo, Mi, and MM groups, respectively (P = 0.04 for MM vs. Mi). During the first day, patients with BD for the groups Mo, Mi, and MM were 34.3%, 36.4%, and 21.2%, respectively (P = NS or not significant), whereas during the second day, these percentages were 38%, 38.5%, and 24%, respectively (P = NS). The data demonstrate that the beneficial effects of morphine in controlling baseline levels of dyspnea could be improved with the addition of midazolam to the treatment.", "To evaluate the efficacy of a mild anxiolytic, alprazolam, in relieving dyspnea, we conducted a randomized, placebo-controlled double-blind study on patients with chronic obstructive lung disease. Twenty-four patients had alprazolam (0.5 mg bid) or placebo administered for one week, followed by placebo for one week, then either placebo or alprazolam for the third week. Assessment tests were performed at the outset, end of the first and second weeks, and finally end of the third week. The parameters measured were: pulmonary function, exercise testing on a bicycle ergometer, and the distance covered in a 12 minute walk. Subjective sensations of dyspnea at rest and during guarded exercise, as well as subjective feelings of calmness or anxiety were also recorded. There was no difference in mechanical lung function, but the PO2 tended to decrease and PCO2 to increase after alprazolam administration. The maximum exercise level attained and the distance covered in the 12 minute walk was unchanged. The subjective perception of dyspnea was the same before and after alprazolam, at rest and during exercise. We conclude that alprazolam is not effective in relieving exercise dyspnea in patients with obstructive lung disease." ]

[ "9101627", "2666559", "9404589", "10268818", "15787665", "2778913", "11333990", "14500058", "9647874", "10888969", "12473876", "12119210", "10514155", "12624611", "3720755", "15951715", "1925430", "2115348", "6849473", "15885845", "11136682", "7742677", "12384828", "8124120", "21432327", "12657339", "4046137", "9540015", "15894901", "2057468", "11182214", "7472698", "15823786", "1328367", "16277797", "15213209", "7989900", "11821367", "7856780", "9290271", "8280188", "8319521", "10447232", "1599343", "16513919", "11716652", "7050440" ]

[ "Effectiveness of two preventive interventions for coronary heart disease in primary care.", "Addition of non-pharmacological methods of treatment in patients on antihypertensive drugs: results of previous medication, laboratory tests and life quality.", "The Family Atherosclerosis Risk Intervention Study (FARIS): risk factor profiles of patients and their relatives following an acute cardiac event.", "The effects of patient characteristics and beliefs on responses to behavioral interventions for control of chronic diseases.", "Teaching and motivating patients to control their risk factors retards progression of cardiovascular as well as microvascular sequelae of Type 2 diabetes mellitus- a randomized prospective 8 years follow-up study.", "Primary prevention of hypertension by nutritional-hygienic means. Final report of a randomized, controlled trial.", "Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.", "Look AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in type 2 diabetes.", "Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol.", "Exercise and weight loss reduce blood pressure in men and women with mild hypertension: effects on cardiovascular, metabolic, and hemodynamic functioning.", "Non-pharmacological treatment of hypertension in primary health care: a 2-year open randomized controlled trial of lifestyle intervention against hypertension in eastern Finland.", "One-year community-based education program for hypercholesterolemia in middle-aged Japanese: a long-term outcome at 8-year follow-up.", "Behavioural counselling in general practice for the promotion of healthy behaviour among adults at increased risk of coronary heart disease: randomised trial.", "Effectiveness of multidisciplinary lifestyle intervention for hypertension: a randomised controlled trial.", "The multifactor primary prevention trial in Göteborg, Sweden.", "The effects of a worksite chronic disease prevention program.", "The effect of a weight reduction program on cardiovascular risk factors among overweight hypertensives in primary health care.", "Preliminary trial of the effect of general practice based nutritional advice.", "Five-year blood pressure control and mortality following health education for hypertensive patients.", "Long-term (1- and 2-year) effects of lifestyle intervention in type 2 diabetes relatives.", "Women's Healthy Lifestyle Project: A randomized clinical trial: results at 54 months.", "The impact of health care advice given in primary care on cardiovascular risk. CELL Study Group.", "Effects of lifestyle modifications on patients with type 2 diabetes: the Japan Diabetes Complications Study (JDCS) study design, baseline analysis and three year-interim report.", "Effectiveness of health checks conducted by nurses in primary care: results of the OXCHECK study after one year. Imperial Cancer Research Fund OXCHECK Study Group.", "Non-pharmacological intervention study of hypercholesterolemia among middle-aged people.", "Effect of individual counseling on physical activity fitness and health: a randomized controlled trial in a workplace setting.", "Multifactorial primary prevention of cardiovascular diseases in middle-aged men. Risk factor changes, incidence, and mortality.", "Lifestyle intervention in overweight individuals with a family history of diabetes.", "Effects of a lifestyle programme on ambulatory blood pressure and drug dosage in treated hypertensive patients: a randomized controlled trial.", "The Tromsø Survey: the Family Intervention study--the effect of intervention on some coronary risk factors and dietary habits, a 6-year follow-up.", "Randomised controlled trial evaluating the effectiveness of behavioural interventions to modify cardiovascular risk factors in men and women with impaired glucose tolerance: outcomes at 6 months.", "Comparison of a lifestyle modification program with propranolol use in the management of diastolic hypertension.", "Effects of the mediterranean lifestyle program on multiple risk behaviors and psychosocial outcomes among women at risk for heart disease.", "Life style changes improve insulin resistance in hyperinsulinaemic subjects: a one-year intervention study of hypertensives and normotensives in Dalby.", "Beneficial effects of short-term nutritional counselling at the primary health-care level among Brazilian adults.", "Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial.", "The efficacy of multiple risk factor intervention in treated hypertensive men during long-term follow up. Risk Factor Intervention Study Group.", "Pragmatic randomized trial of home visits by a nurse to elderly people with hypertension in Mexico.", "Take heart: results from the initial phase of a work-site wellness program.", "A hypertension control program in Yu-Chi, Taiwan: preliminary results.", "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 maintenance of improved metabolic control after intensified diet therapy in recent type 2 diabetes.", "Improved fibrinolysis by intense lifestyle intervention. A randomized trial in subjects with impaired glucose tolerance.", "Nonpharmacologic intervention to reduce blood pressure in older patients with mild hypertension.", "Randomized controlled trial on lifestyle modification in hypertensive patients.", "Evaluation of a multicomponent workplace health promotion program conducted in Japan for improving employees' cardiovascular disease risk factors.", "Multiple risk factor intervention trial. Risk factor changes and mortality results. Multiple Risk Factor Intervention Trial Research Group." ]

[ "1. To compare a patient-centred, self-directive intervention with conventional care; 2. To evaluate longitudinal within-group changes of coronary heart disease risk.\n Risk factor changes were evaluated in 110 men with high coronary heart disease risk attending a one year intervention study in general practice. The 22 participating general practice centres were randomly allocated to follow either a patient-centred, self-directive intervention or a conventional approach.\n No significant between-group differences were found in any single risk factor or in the combined risk of coronary heart disease. The improvement of total risk from screening time to conclusion of the study corresponded with changes of relative risks of CHD to 0.64 (95% CI: 0.54-0.77) and 0.65 (0.54-0.77) in the patient-centred, self-directive and the conventional care group respectively (p < 0.0001 in both groups).\n Everyday general practice clinical work seems as efficacious as a specific intervention method based on currently advocated behaviour change principles.", "Four hundred patients from eight health centres were recruited for this 2-year study on the possible replacement of antihypertensive drugs by non-pharmacological therapy. All the patients were given a device to measure their blood pressure at home and had monthly checks at a health centre. Two hundred patients on antihypertensive drugs (G1) started additional non-pharmacological therapy after 1 year in the study, while the rest (G2) had used it from the beginning. Antihypertensive drugs were withdrawn according to predetermined criteria. The drop-out rate was 1.5% each year. Medication was withdrawn completely from 42.7% of G1, and in 21.5% it was withheld for at least 18 months. The corresponding figures for G2 were 46.4% and 25.5% respectively. Most of the medication withdrawal in G1 occurred during the first year, when the group's management consisted solely of blood pressure measurements at home and frequent visits to the health centre. Serum triglycerides decreased on non-pharmacological treatment in both sexes in both groups. Life quality improved, particularly for the group (n = 173) that had the drugs withdrawn.", "Relatives of patients with coronary heart disease have a heightened risk of cardiovascular disease. Attendance at a family-based screening clinic after an acute cardiac event could motivate patients and relatives to modify their lifestyles.\n The Family Atherosclerosis Risk Intervention Study (FARIS) aimed to determine (i) whether a high proportion of patients and relatives would attend a special screening and prevention programme; (ii) whether the risk factor profiles of relatives would be worse than those in the general community; and (iii) whether ongoing management of patients and families together in a special clinic would improve risk factor profiles.\n Consecutive patients, together with spouse, siblings and offspring, aged 18 to 69 years, were randomly allocated three months after an acute cardiac event to attend a special outpatient clinic, a screening and advice group, or a control group. Risk factor measures were total cholesterol, HDL cholesterol (HDLC), systolic blood pressure (SBP), body mass index (BMI) and smoking behaviour. This paper presents the risk factor profiles of all FARIS attenders and compares those of family members, age adjusted, with risk factors measured in a multicentre urban cross-sectional survey conducted in the same period. Differences between groups were compared using t-tests for numerical variables and ANOVA and chi-square for categorical variables.\n Six hundred and twenty-eight patients and 1723 family members were enrolled, representing 85.9% and 82.7% of eligible patients and relatives respectively. Risk factors were significantly worse amongst family members than among those in the population survey.", "Tests of behavioral interventions seldom examine changes in health beliefs and behaviors thought to be prerequisites of improved outcome health states and they do not attempt to specify how patient characteristics or pretest measures influence responses to the intervention. In this study an experimental nursing intervention, its impact on hypertensive patients' beliefs about their disease, efficacy of medications and diet, as well as blood pressure and weight are described. Among patients from the experimental group, the ability of selected pretest variables to predict clinical outcomes and changes in clinical health states was evaluated. The intervention was successful in lowering diastolic blood pressure and altering certain beliefs held by the patients. The pretest characteristics were not successful in explaining hypertensive patients' responses to the intervention. Explanations for this are pursued through remarks from the content analysis of the intervention protocol. From these observations, the original health belief model was revised. The discussion concludes with a set of research questions that may prove promising for future research.", "To examine whether motivating patients to gain expertise and closely follow their risk parameters will attenuate the course of microvascular and cardiovascular sequelae of diabetes.\n A randomized prospective study on 165 patients with diabetes mellitus Type 2, hypertension (> 140/90 mmHg) and hyperlipidaemia (LDL-C > 3 mmol/l), referred for consultation to a diabetes clinic in an academic hospital. Patients were randomly allocated to standard consultation (SC) or to a patient participation (PP) and teaching programme. Follow-up continued by primary care physicians.\n The mean follow-up was 7.7 years. SC group patients each attended eight annual consultations. The PP patients initiated on average 1.2 +/- 0.8 additional consultations per annum. The relative risk (RR) over 8 years, for the combined cardiovascular event index in the intervention (PP) vs. the control (SC) group was 0.65 (95% CI 0.41-0.89, P = 0.001). Nephropathy developed in 14 vs. 7 patients in the SC and PP groups, respectively, RR 0.50 (95% CI 0.28-0.85, P = 0.02), retinopathy developed in 35 vs. 21 patients, RR 0.60 (95% CI 0.21-0.82, P = 0.03). Throughout the study, period blood pressure, LDL-C and HbA1c were significantly lower in the PP than in the SC patients.\n Well-informed and motivated patients, were more successful in maintaining good control of their risk factors, resulting in reduced cardiovascular risk and slower progression of microvascular disease.", "A 5-year trial involving 201 men and women with high-normal blood pressure at baseline demonstrated the ability to reduce the incidence of hypertension in participants randomized to nutritional-hygienic intervention compared with a control group. The incidence of hypertension was 8.8% among 102 intervention group participants vs 19.2% among 99 control group members. The odds ratio for the incidence of hypertension in the control group was 2.4. Mean trial blood pressure also was lower in the intervention compared with the control group (-1.2 and -1.9 mm Hg, respectively, for diastolic blood pressure at work-site and office visits and -1.3 and -2.0 mm Hg, respectively, for systolic blood pressure at the two sites). Net weight loss in the intervention group averaged 2.7 kg during the trial; sodium intake was reduced by 25% and reported alcohol intake decreased by 30%. The majority of intervention participants also reported an increase in physical activity. Effect on blood pressure was related particularly to degree of weight loss. Results indicate that even a moderate reduction in risk factors for hypertension among hypertension-prone individuals contributes to the primary prevention of the disease.", "Type 2 diabetes mellitus is increasingly common, primarily because of increases in the prevalence of a sedentary lifestyle and obesity. Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known.\n We randomly assigned 522 middle-aged, overweight subjects (172 men and 350 women; mean age, 55 years; mean body-mass index [weight in kilograms divided by the square of the height in meters], 31) with impaired glucose tolerance to either the intervention group or the control group. Each subject in the intervention group received individualized counseling aimed at reducing weight, total intake of fat, and intake of saturated fat and increasing intake of fiber and physical activity. An oral glucose-tolerance test was performed annually; the diagnosis of diabetes was confirmed by a second test. The mean duration of follow-up was 3.2 years.\n The mean (+/-SD) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group (P<0.001 for both comparisons between the groups). The cumulative incidence of diabetes after four years was 11 percent (95 percent confidence interval, 6 to 15 percent) in the intervention group and 23 percent (95 percent confidence interval, 17 to 29 percent) in the control group. During the trial, the risk of diabetes was reduced by 58 percent (P<0.001) in the intervention group. The reduction in the incidence of diabetes was directly associated with changes in lifestyle.\n Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects.", "Overweight and obesity are major contributors to both type 2 diabetes and cardiovascular disease (CVD). Moreover, individuals with type 2 diabetes who are overweight or obese are at particularly high risk for CVD morbidity and mortality. Although short-term weight loss has been shown to ameliorate obesity-related metabolic abnormalities and CVD risk factors, the long-term consequences of intentional weight loss in overweight or obese individuals with type 2 diabetes have not been adequately examined. The primary objective of the Look AHEAD clinical trial is to assess the long-term effects (up to 11.5 years) of an intensive weight loss program delivered over 4 years in overweight and obese individuals with type 2 diabetes. Approximately 5000 male and female participants who have type 2 diabetes, are 45-74 years of age, and have a body mass index >or=25 kg/m(2) will be randomized to one of the two groups. The intensive lifestyle intervention is designed to achieve and maintain weight loss through decreased caloric intake and increased physical activity. This program is compared to a control condition given diabetes support and education. The primary study outcome is time to incidence of a major CVD event. The study is designed to provide a 0.90 probability of detecting an 18% difference in major CVD event rates between the two groups. Other outcomes include components of CVD risk, cost and cost-effectiveness, diabetes control and complications, hospitalizations, intervention processes, and quality of life.", "Guidelines established by the National Cholesterol Education Program (NCEP) promote exercise and weight loss for the treatment of abnormal lipoprotein levels. Little is known, however, about the effects of exercise or the NCEP diet, which is moderately low in fat and cholesterol, in persons with lipoprotein levels that place them at high risk for coronary heart disease.\n We studied plasma lipoprotein levels in 180 postmenopausal women, 45 through 64 years of age, and 197 men, 30 through 64 years of age, who had low high-density lipoprotein (HDL) cholesterol levels (< or =59 mg per deciliter in women and < or =44 mg per deciliter in men) and moderately elevated levels of low-density lipoprotein (LDL) cholesterol (>125 mg per deciliter but <210 mg per deciliter in women and >125 mg per deciliter but <190 mg per deciliter in men). The subjects were randomly assigned to aerobic exercise, the NCEP Step 2 diet, or diet plus exercise, or to a control group, which received no intervention.\n Dietary intake of fat and cholesterol decreased during the one-year study (P<0.001), as did body weight, in women and men in either the diet group or the diet-plus-exercise group, as compared with the controls (P<0.001) and the exercise group (P<0.05), in which dietary intake and body weight were unchanged. Changes in HDL cholesterol and triglyceride levels and the ratio of total to HDL cholesterol did not differ significantly among the treatment groups, for subjects of either sex. The serum level of LDL cholesterol was significantly reduced among women (a decrease of 14.5+/-22.2 mg per deciliter) and men (a decrease of 20.0+/-17.3 mg per deciliter) in the diet-plus-exercise group, as compared with the control group (women had a decrease of 2.5+/-16.6 mg per deciliter, P<0.05; men had a decrease of 4.6+/-21.1 mg per deciliter, P<0.001). The reduction in LDL cholesterol in men in the diet-plus-exercise group was also significant as compared with that among the men in the exercise group (3.6+/-18.8 mg per deciliter, P<0.001). In contrast, changes in LDL cholesterol levels were not significant among the women (a decrease of 7.3+/-18.9 mg per deciliter) or the men (10.8+/-18.8 mg per deciliter) in the diet group, as compared with the controls.\n The NCEP Step 2 diet failed to lower LDL cholesterol levels in men or women with high-risk lipoprotein levels who did not engage in aerobic exercise. This finding highlights the importance of physical activity in the treatment of elevated LDL cholesterol levels.", "Lifestyle modifications have been recommended as the initial treatment strategy for lowering high blood pressure (BP). However, evidence for the efficacy of exercise and weight loss in the management of high BP remains controversial.\n One hundred thirty-three sedentary, overweight men and women with unmedicated high normal BP or stage 1 to 2 hypertension were randomly assigned to aerobic exercise only; a behavioral weight management program, including exercise; or a waiting list control group. Before and following treatment, systolic and diastolic BPs were measured in the clinic, during daily life, and during exercise and mental stress testing. Hemodynamic measures and metabolic functioning also were assessed.\n Although participants in both active treatment groups exhibited significant reductions in BP relative to controls, those in the weight management group generally had larger reductions. Weight management was associated with a 7-mm Hg systolic and a 5-mm Hg diastolic clinic BP reduction, compared with a 4-mm Hg systolic and diastolic BP reduction associated with aerobic exercise; the BP for controls did not change. Participants in both treatment groups also displayed reduced peripheral resistance and increased cardiac output compared with controls, with the greatest reductions in peripheral resistance in those in the weight management group. Weight management participants also exhibited significantly lower fasting and postprandial glucose and insulin levels than participants in the other groups.\n Although exercise alone was effective in reducing BP, the addition of a behavioral weight loss program enhanced this effect. Aerobic exercise combined with weight loss is recommended for the management of elevated BP in sedentary, overweight individuals.", "To assess whether lifestyle counselling is effective in non-pharmacological treatment of hypertension in primary health care.\n Open randomized controlled trial.\n Ten municipal primary health care centres in eastern Finland.\n Seven hundred and fifteen subjects aged 25-74 years with systolic blood pressure 140-179 mmHg and/or diastolic blood pressure 90-109 mmHg or antihypertensive drug treatment.\n Systematic health counselling given by local public health nurses for 2 years.\n Blood pressure, lipids and lifestyle data were collected annually.\n Among participants with no antihypertensive drug treatment, the net reductions after 1 year both in systolic blood pressure [-2.6 mmHg; 95% confidence interval (CI), -4.7 to -0.5 mmHg] and in diastolic blood pressure (-2.7 mmHg; 95% CI, -4.0 to -1.4 mmHg) were significant in favour of the intervention group. This difference in blood pressure change was maintained during the second year. In participants with antihypertensive drug treatment, no significant difference in blood pressure reduction was seen between the groups during the study.\n A relatively modest, but systematic counselling in primary health care can, at least among untreated hypertensive subjects, produce reductions in blood pressure levels that are modest for the individual, but very important from the public health point of view.", "To examine a long-term effect of community-based education program for hypercholesterolemia and an effect modification by apolipoprotein E polymorphism, we conducted a 1-year randomized clinical trial with 8 year-follow-up. One hundred four persons aged 40-64 years who had serum total cholesterol levels between 6.21 and 7.73 mmol/l (240 and 299 mg/dl) in 1988-89 cardiovascular risk surveys were enrolled in the trial. The intervention group (n=51, 82% for women) attended eight education classes in 1 year, while the control group (n=53, 85% for women) attended only two classes. Both groups were invited to the subsequent annual surveys. The mean serum cholesterol was 0.24-0.26 mmol/l less in the intervention than in the control group at both 6 month and 1 year (P=0.03, each) while the proportion of subjects using hypolipidemic agents was 0 and 6% in both groups, respectively. During 8-year follow-up, the probability of using hypolipidemic agents and/or total cholesterol > or =7.76 mmol/l was 51% in the education group and 69% in the control group; the risk ratio in the intervention vs control groups was 0.62 (95% CI: 0.36-1.06). When stratified by the apolipoprotein E polymorphism examined for 78% of the subjects, the risk ratio was 0.61 (0.31-1.18) among subjects without e4 allele (n=59) and 0.55 (0.14-2.14) among those with e4 allele (n=22). The intervention group had reduced intake of egg, fish egg, butter, mayonnaise and fatty meat compared to the control group at 6-month, 1- and 8-year follow-up. In conclusion, our community-based program was effective in reducing serum total cholesterol levels non-pharmacologically during the first year, and also reduced the likelihood of progressive worsening of hypercholesterolemia during the subsequent 8 years, regardless of the apolipoprotein E polymorphism.", "To measure the effect of behaviourally oriented counselling in general practice on healthy behaviour and biological risk factors in patients at increased risk of coronary heart disease.\n Cluster randomised controlled trial.\n 883 men and women selected for the presence of one or more modifiable risk factors: regular cigarette smoking, high serum cholesterol concentration (6.5-9.0 mmol/l), and high body mass index (25-35) combined with low physical activity.\n Brief behavioural counselling, on the basis of the stage of change model, carried out by practice nurses to reduce smoking and dietary fat intake and to increase regular physical activity.\n Questionnaire measures of diet, exercise, and smoking habits, and blood pressure, serum total cholesterol concentration, weight, body mass index, and smoking cessation (with biochemical validation) at 4 and 12 months.\n Favourable differences were recorded in the intervention group for dietary fat intake, regular exercise, and cigarettes smoked per day at 4 and 12 months. Systolic blood pressure was reduced to a greater extent in the intervention group at 4 but not at 12 months. No differences were found between groups in changes in total serum cholesterol concentration, weight, body mass index, diastolic pressure, or smoking cessation.\n Brief behavioural counselling by practice nurses led to improvements in healthy behaviour. More extended counselling to help patients sustain and build on behaviour changes may be required before differences in biological risk factors emerge.", "Lifestyle factors like weight, alcohol consumption, salt intake and physical activity have shown to be important in treating hypertension. There have been made some randomised trials about the effects of lifestyle interventions, but the numbers of patients have been relatively small and the durations of follow-ups have been short. No controlled trials assessing the effects of lifestyle intervention in a rehabilitation setting have been reported. In this study, the effects of multidisciplinary lifestyle intervention in rehabilitation centres among middle-aged hypertensive employees were described. A total of 731 hypertensives from 45 worksites were randomised to lifestyle intervention in a rehabilitation centre or to usual care in an occupational or primary health-care centre for 12 months. Standard measurements were conducted before the intervention and 1-year later. Blood pressure (BP) levels were clearly reduced in the intervention group, while only minor changes were observed in the control group. The net changes between the two groups both for systolic and diastolic BPs were -2.1 mmHg (95% confidence intervals (CI) -4.0 to -0.1) and -1.5 mmHg (95% CI -2.6 to -0.4), respectively. The net changes were greater among men than women. The multidisciplinary lifestyle intervention in a rehabilitation centre setting produced significant reductions in BP among middle-aged employees with hypertension.", "The effect of a multifactorial intervention programme on coronary heart disease (CHD), stroke incidence and total mortality was determined in a random sample of men, 47-55 years old at entry. The intervention group comprised 10 004 men, and the two control groups were of similar size. The intervention consisted of antihypertensive treatment in subjects with screening blood pressure above 175 mmHg systolic or 115 mmHg diastolic, dietary advice to men with serum cholesterol levels above 260 mg per 100 ml (= 6.8 mMol l-1), advice to stop smoking to subjects who smoked more than 15 cigarettes per day. The intervention was applied for 10 years during which time CHD and stroke incidence and mortality were followed by means of special registers. Participation rate at first screening examination was 75%. The risk factor levels, i.e. blood pressure, serum cholesterol and smoking decreased markedly during 10 years in the intervention group, but also among the control groups. Total mortality, stroke and CHD incidence did not differ significantly between the intervention group and any of the two control groups. We conclude that a decrease has taken place in all three major risk factors for CHD in the general male population in Göteborg, Sweden. Strategies other than intervention on high-risk individuals must be chosen if a major impact on disease incidence is to be achieved in the general population.", "This study determined the behavioral and clinical impact of a worksite chronic disease prevention program.\n Working adults participated in randomized clinical trial of an intensive lifestyle intervention. Nutrition and physical activity behavior and several chronic disease risk factors were assessed at baseline, 6 weeks, and 6 months.\n Cognitive understanding of the requirements for a healthy lifestyle increased at the end of the program. Program participants significantly improved their cognitive understanding of good nutrition and physical activity and had significantly better nutrition and physical activity behavior at both 6 weeks and 6 months. Participants had significantly lower body fat, blood pressure, and cholesterol.\n This worksite chronic disease prevention program can significantly increase health knowledge, can improve nutrition and physical activity, and can improve many employee health risks in the short term.", "The aim of the study was to test the effect of a nonpharmacological weight reduction program on cardiovascular risk factors among overweight hypertensives in a primary health care setting. Forty-nine overweight hypertensive patients completed the 12-month program. The patients were randomly allocated into either intervention or control groups. The examinations included interviews by a nutritionist, pertinent laboratory tests, and a medical examination. The intervention involved an individually planned energy-restricted diet of 1000-1500 kcal per day, weekly discussions, and various leaflets on diet modification and on increase of physical activity. The mean body weight was reduced by 5 kg in the intervention group, but remained unchanged in the control group. The intervention group reduced their fat intake by 14 g/day while the control group increased it by 9 g/day on the average. In the intervention group, the total serum cholesterol decreased, HDL-cholesterol increased and triglycerides decreased significantly. The systolic blood pressure fell by 8 mm Hg and 15 mm Hg in the intervention and control groups, respectively. The diastolic blood pressure fell on average by 11 mm Hg in both groups. The results demonstrate the comprehensive weight reduction program to be effective in the control of cardiovascular risk factors.", "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.", "Three health education interventions for urban poor hypertensive patients were introduced sequentially in a randomized factorial design: 1) an exit interview to increase understanding of and compliance with the prescribed regimen; 2) a home visit to encourage a family member to provide support for the patient's regimen; and 3) invitations to small group sessions to increase the patient's confidence and ability to manage his/her problem. Previous evaluation of the initial two-year experience demonstrated a positive effect of the educational program on compliance with the medical treatment and blood pressure control. Data accumulated over an additional three years, including mortality analysis, are now presented. The study group consisted of the same cohort of 400 ambulatory hypertensive outpatients in the eight experimental and control groups. The five-year analysis shows a continuing positive effect on appointment keeping, weight control, and blood pressure control. All-cause life table mortality rate was 57.3 per cent less for the experimental group compared to the control group (12.9/100 vs 30.2/100, p less than .05), while the hypertension-related mortality rate was 53.2 per cent less (8.9/100 vs 19.0/100, p less than .01). The results from this longitudinal study provide evidence to encourage health practitioners to utilize such educational programs in the long-term management and control of high blood pressure.", "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 Women's Healthy Lifestyle Project Clinical Trial tested the hypothesis that reducing saturated fat and cholesterol consumption and preventing weight gain by decreased caloric and fat intake and increased physical activity would prevent the rise in LDL cholesterol and weight gain in women during perimenopause to postmenopause.\n There were 275 premenopausal women randomized into the assessment only group and 260 women into the intervention group. The mean age of participants at baseline was 47 years, and 92% of the women were white. The mean LDL cholesterol was 115 mg/dL at baseline, and mean body mass index was 25 kg/m(2). The follow-up through 54 months was excellent. By 54 months, 35% of the women had become postmenopausal. At the 54-month examination, there was a 3.5-mg/dL increase in LDL cholesterol in the intervention group and an 8.9-mg/dL increase in the assessment-only group (P:=0.009). Weight decreased 0.2 lb in the intervention and increased 5.2 lb in the assessment-only group (P:=0.000). Triglycerides and glucose also increased significantly more in the assessment-only group than in the intervention group. Waist circumference decreased 2.9 cm in the intervention compared with 0.5 cm in the assessment-only group (P:=0.000).\n The trial was successful in reducing the rise in LDL cholesterol during perimenopause to postmenopause but could not completely eliminate the rise in LDL cholesterol. The trial was also successful in preventing the increase in weight from premenopause to perimenopause to postmenopause. The difference in LDL cholesterol between the assessment and intervention groups was most pronounced among postmenopausal women and occurred among hormone users and nonusers.", "To evaluate the additional benefit of \"intensive\" health care advice through six group sessions, compared with the advice usually offered to subjects with multiple risk factors for cardiovascular disease.\n Prospective, randomised controlled clinical study lasting 18 months.\n 681 subjects aged 30-59 years, with at least two cardiovascular risk factors in addition to moderately high lipid concentrations: total cholesterol > or = 6.5 mmol/l on three occasions, triglycerides < 4.0 mmol/l, and ratio of low density lipoprotein cholesterol to high density lipoprotein cholesterol > 4.0. Most (577) of the subjects were men.\n Percentage reduction in total cholesterol concentration (target 15%); quantification of the differences between the two types of health care advice (intensive v usual) for the Framingham cardiovascular risk and for individual risk factors.\n In the group receiving intensive health care advice total cholesterol concentration decreased by 0.15 mmol/l more (95% confidence interval 0.04 to 0.26) than in the group receiving usual advice. The overall Framingham risk dropped by 0.068 more (0.014 to 0.095) in the group receiving intensive advice, and most of the risk factors showed a greater change in a favourable direction in this group than in the group receiving usual advice, but the differences were seldom significant. The results from questionnaires completed at the group sessions showed that the subjects improved their lifestyle and diet.\n Limited additional benefit was gained from being in the group receiving the intensive health care advice. It is difficult to make an important impact on cardiovascular risk in primary care by using only the practice staff. Better methods of communicating the messages need to be devised.", "Lifestyle modifications may affect the development of diabetes and prevent complications. However, there is no direct evidence to show that lifestyle intervention is beneficial for patients with established type 2 diabetes.\n The ultimate goal is to determine whether long-term lifestyle intervention can improve glycemic control and prevent complications in patients with type 2 diabetes. This initial report on a multi-year study describes protocols and the analysis of baseline data and three-year interim results.\n The study was a randomized, controlled, multi-centre, prospective intervention trial. The trial included patients from 59 Japanese institutes specializing in diabetes care.\n The study enrolled 2 205 patients with previously diagnosed type 2 diabetes.\n The lifestyle modification program included intensive lifestyle management at each outpatient clinic visit and frequent telephone counseling. The intervention group received educational materials concerning the importance of lifestyle and behavioural changes, a diary to record progress of laboratory and other data, and a pedometer.\n Parameters and indices related to glycemic control, diabetic complications, dyslipidemia, hypertension, obesity, and atherosclerosis were measured several times a year.\n Small but significant differences in HbA1c levels between the intervention (INT) and conventional (CON) therapy groups appeared as early as two years after the start of intervention and were maintained in the third year (CON group, 7.78 +/- 1.27 % vs. INT group, 7.62 +/- 1.20 %, the initial HbA1c level was 7.80 +/- 1.42 % for the CON group and 7.68 +/- 1.28 % for the INT group). Data on differences in occurrence of micro- or macrovascular complications are not yet available.\n The effect of lifestyle modification on improving the glycemic control of patients with established type 2 diabetes mellitus was small but significant three years after initiation of the intervention.", "To assess the effectiveness of health checks by nurses in reducing risk factors for cardiovascular disease in patients from general practice.\n Randomised controlled trial.\n Five urban general practices in Bedfordshire.\n 2136 patients receiving an initial health check in 1989-91 and scheduled to be re-examined one year later in 1990-2 (intervention group); 3988 patients receiving an initial health check in 1990-2 (control group). All patients were aged 35-64 years at recruitment in 1989.\n Serum total cholesterol concentration, blood pressure, body mass index, confirmed smoking cessation.\n Mean serum total cholesterol was 2.3% lower in the intervention group than in the controls (difference 0.14 mmol/l (95% confidence interval 0.08 to 0.20)); the difference was greater in women (3.2%, P < 0.0001) than men (1.0%, P = 0.18). There was no significant difference in smoking prevalence, quit rates, or body mass index. Systolic and diastolic blood pressure were 2.5% and 2.4% lower respectively in the intervention group. The proportion of patients with diastolic blood pressure > or = 100 mm Hg was 2.6% (55/2131) in the intervention group and 3.4% (137/3987) in the controls (difference 0.9% (0.0 to 1.7)); the proportion with total cholesterol concentration > or = 8 mmol/l 4.8% (100/2068) and 7.6% (295/3905) (difference 2.7% (1.5 to 4.0)); and that with body mass index > or = 30 12.4% (264/2125) and 14.0% (559/3984) (difference 1.6% (-0.2 to 3.4)).\n General health checks by nurses are ineffective in helping smokers to stop smoking, but they help patients to modify their diet and total cholesterol concentration. The public health importance of this dietary change depends on whether it is sustained.", "Middle-aged people with a serum total cholesterol of more than 220 mg/dl at the latest health examination (n=197) at a chemical company were invited to join a health education program for 6 months. Participants meeting inclusion criteria were randomly assigned to an intervention (n=96) and a control group (n=92). Periodical interviews and blood tests were performed every 2 months for both groups. The intervention group was educated by health professionals in the factories through programs developed for hypercholesterolemia. After a 6-month intervention, the reduction of cholesterol levels and the differences between the groups were analysed.The mean total cholesterol (TCH) levels at the baseline measurement were 239.7 mg/dl in the intervention group and 236.5 mg/dl in the control group. During the intervention period, decreased levels of TCH were 27.1 mg/dl for the intervention group and 18.5 mg/dl for the control group. Declines in body weight, TCH and triglyceride levels in the intervention group were significantly larger than those in the control group. The decline of apoprotein-B was also significantly larger in the intervention group while high-density lipoprotein cholesterol levels essentially did not change.The health education by health professionals proved to be useful in reducing the risk factor levels for coronary heart disease. These results suggest that health education would also be useful against other major risk factors in cardiovascular diseases.", "Physical inactivity and obesity are major public health problems. Our objective was to investigate the effectiveness of an individual counseling intervention at the workplace on physical activity fitness and health. Counseling content derived from the Patient-centered Assessment and Counseling for Exercise and Nutrition (PACE) program.\n A total of 299 employees of three municipal services in the Dutch town of Enschede were randomly allocated into intervention (n =131) and control group (n =168). Over a 9-month period, intervention group subjects were offered seven counseling sessions. Counseling was based on the individual's stage of behavioral change using PACE physical activity and nutrition protocols. Subjects in both the intervention and control group received written information about several lifestyle factors. Primary outcome measures were physical activity (total energy expenditure, during sports activities, during physical activity leisure time other than sports, and meeting the moderate-intensity public health recommendations); cardiorespiratory fitness; and prevalence of musculoskeletal symptoms. Secondary outcome measures were body composition (body mass index [BMI], and percentage of body fat measured via skinfold thicknesses); blood pressure; and blood cholesterol.\n There were significant positive effects on total energy expenditure, physical activity during sports, cardiorespiratory fitness, percentage of body fat, and blood cholesterol. No effects were found for the proportion of subjects meeting the public health recommendation of moderate-intensity physical activity, physical activity during leisure time other than sports, prevalence of musculoskeletal symptoms, body mass index, and blood pressure.\n Individual face-to-face counseling at the workplace based on PACE protocols positively influenced physical activity levels and some components of physical fitness. The implementation of workplace counseling programs for individuals should therefore be promoted.", "In a randomized five-year multifactorial primary prevention trial of vascular diseases, hyperlipidemias, hypertension, smoking, obesity, and abnormal glucose tolerance of the high-risk test group (n = 612 men) were treated with dietetic-hygienic measures and hypolipidemic (mainly probucol and clofibrate) and antihypertensive (mainly diuretics and beta-blockers) agents. A matched high-risk control group (n = 610) and a low-risk control group (n = 593) were not treated. The program markedly improved the risk factor status, yet the five-year coronary incidence tended to be higher in the intervention group than in the control group (3.1% vs 1.5%), while the stroke incidence was significantly reduced (1.3% vs 0%). The coronary events tended to be accumulated in subgroups treated with beta-blocking agents or clofibrate, but there were few in those receiving probucol or diuretics. Thus, the intervention program significantly reduced development of stroke, but the occurrence of cardiac events was not prevented. Possible adverse drug effects offsetting the probable benefit of improved risk profile are not excluded.", "To assess the effect of lifestyle intervention over 2 years on changes in weight, coronary heart disease (CHD) risk factors, and incidence of diabetes in overweight individuals with a parental history of diabetes.\n Participants (n = 154), who were 30-100% over ideal body weight, had one or both parents with diabetes, and were currently nondiabetic, were randomly assigned to 2-year treatments focused on diet (decreasing calories and fat intake), exercise (goal of 1,500 kcal/week of moderate activity), or the combination of diet plus exercise or to a no-treatment control group. Subjects were reassessed at 6 months, 1 year, and 2 years.\n At 6 months, the groups differed significantly on measures of eating, exercise, and fitness; weight losses in the diet and diet-plus-exercise groups were significantly greater than in the exercise and control conditions. Weight losses were associated with positive changes in CHD risk factors. After 6 months, there was gradual deterioration of behavioral and physiological changes, so that at 2 years, almost no between-group differences were maintained. Differences between groups in risk of developing diabetes were of borderline significance (P = 0.08). Strongest predictors were impaired glucose tolerance at baseline, which was positively related to risk of developing diabetes, and weight loss from baseline to 2 years, which was negatively related; in all treatment groups, a modest weight loss of 4.5 kg reduced the risk of type 2 diabetes by approximately 30% compared with no weight loss.\n Although initially successful, the interventions studied here were not effective in producing long-term changes in behavior, weight, or physiological parameters. However, weight loss from 0 to 2 years reduced the risk of developing type 2 diabetes. Since modest weight loss significantly reduced risk of type 2 diabetes, further research is needed to determine how best to increase the percentage of subjects achieving at least a modest weight loss.", "To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals.\n Randomized controlled trial.\n Research studies unit.\n Overweight hypertensive patients, receiving one or two antihypertensive drugs, were recruited by advertising, and allocated randomly to a usual care group (controls; n = 118) or a lifestyle modification group (programme group; n = 123).\n A 4-month programme of weight loss, a low-sodium 'Dietary Approaches to Stop Hypertension'-type diet with added fish, physical activity and moderation of alcohol intake. After 4 months, if mean 24-h ambulatory blood pressure (ABP) was less than 135/85 mmHg, antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun.\n Antihypertensive drug requirements, ABP, weight, waist girth at 4 months and 1-year follow-up.\n Ninety control group and 102 programme group participants completed the study. Mean 24-h ABP changed after 4 months by -1.0/-0.3 +/- 0.5/0.4 mmHg in controls and -4.1/-2.1 +/- 0.7/0.5 mmHg with the lifestyle programme (P < 0.01). At follow-up, changes in the two groups were not significantly different (4.1/1.3 +/- 1.1/1.0 mmHg in controls; 2.5/-0.1 +/- 1.1/0.8 mmHg in the programme group; P = 0.73). At 4 months, drug withdrawal differed significantly between the groups (P = 0.038) in men (control 44%; programme 66%) but not in women (65 and 64%, respectively; P = 0.964). At follow-up, sex-related differences were not significant, and 41% in the control group and 43% in the programme group maintained drug-withdrawal status. With the programme, net weight loss was 3.3 kg (P < 0.001) at 4 months and 3.0 kg (P < 0.001) at follow-up; respective net decreases in waist girth were 3.3 cm (P < 0.001) and 3.5 cm (P < 0.001).\n A 4-month multifactorial lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term. Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk.", "While most intervention studies on coronary heart disease have focused on the high-risk person only, the present study used the family as the unit of intervention. In the study 1373 high-risk men, ages 30-54 years, were identified on the basis of high total cholesterol (TC) and/or low relative high-density lipoprotein cholesterol (HDL-C) (HDL-C/TC) following the 1979/1980 survey in Tromsø. The men and their families were randomly allocated to a control or intervention condition. The intervention families were given advice on diet, smoking, and exercise. At rescreening in 1986/1987, significantly lower risk factor levels were found in both the intervention men and their spouses compared with those in the control group. For children, the differences were small and mostly nonsignificant. Men, spouses, and children in the intervention group reported more favorable dietary habits than those in the control group. No differences were found in smoking or leisure time physical activity.", "To evaluate the efficacy of interventions to promote a healthy diet and physical activity in people with impaired glucose tolerance (IGT).\n A randomised controlled trial in Newcastle upon Tyne, UK, 1995-98. Participants included 67 adults (38 men; 29 women) aged 24-75 years with IGT. The intervention consisted of regular diet and physical activity counselling based on the stages of change model. Main outcome measures were changes between baseline and 6 months in nutrient intake; physical activity; anthropometric and physiological measurements including serum lipids; glucose tolerance; insulin sensitivity.\n The difference in change in total fat consumption was significant between intervention and control groups (difference -21.8 (95% confidence interval (CI) -37.8 to -5.8) g/day, P=0.008). A significantly larger proportion of intervention participants reported taking up vigorous activity than controls (difference 30.1, (95% CI 4.3--52.7)%, P=0.021). The change in body mass index was significantly different between groups (difference -0.95 (95% CI -1.5 to -0.4) kg/m(2), P=0.001). There was no significant difference in change in mean 2-h plasma glucose between groups (difference -0.19 (95% CI -1.1 to 0.71) mmol/l, NS) or in serum cholesterol (difference 0.02 (95% CI -0.26 to 0.31) mmol/l, NS). The difference in change in fasting serum insulin between groups was significant (difference -3.4 (95% CI -5.8 to -1.1) mU/l, P=0.005).\n After 6 months of intensive lifestyle intervention in participants with IGT, there were changes in diet and physical activity, some cardiovascular risk factors and insulin sensitivity, but not glucose tolerance. Further follow-up is in progress to investigate whether these changes are sustained or augmented over 2 years.", "To compare the management of mild diastolic hypertension (90 to 104 mm Hg) using a nonpharmacologic intervention with that using propranolol or placebo.\n Randomized, placebo-controlled trial with a 2 x 2 factorial design.\n University-based ambulatory care center.\n Two hundred seven men and 105 women, 22 to 59 years of age, 73% white, who had mild diastolic hypertension untreated for at least eight weeks.\n 1) a multicomponent lifestyle modification intervention (lifestyle focus group, or LFG) administered in eight weekly meetings + placebo, 2) LFG + propranolol, 3) propranolol alone, and 4) placebo alone, followed for 12 months.\n Systolic blood pressure (SBP), diastolic blood pressure (DBP), and self-reported adverse effects at each of nine follow-up visits; fasting total cholesterol, triglycerides, and glucose at baseline and 12 months; 24-hour urine sodium (Na+) and potassium (K+), three-day food records and physical activity questionnaire at three and 12 months; and a quality of life questionnaire at 12 months.\n The mean decreases in DBP at 12 months were: 8.5 mm Hg in the LFG + propranolol group; 7.7 mm Hg in the propranolol-only group; 5.9 mm Hg in the placebo-only group; and 5.4 mm Hg in the LFG + placebo group. Repeated-measures analysis of covariance showed that level of baseline DBP (p < 0.0001), time of follow-up (p < 0.0001), and propranolol use (p < 0.0001) were significantly associated with a decrease in DBP at 12 months. Despite reductions in urinary Na+ (-35 mEq; 95% CI = -50, -19), dietary Na+ (-521 mg; 95% CI = -710, -332), total calories ingested (-238; 95% CI = -335, -140), and weight (-1.4 lb; 95% CI = -3.7, +0.8), and significant increases in dietary K+ (+294 mg; 95% CI = +107, +480) and in mets-minutes of exercise (+43; 95% CI = +20, +67) at three months, assignment to the LFG intervention had no effect on DBP at three or 12 months. The subjects assigned to take propranolol more frequently reported fatigue during ordinary activities, sleep disturbance, decrease in sexual activity, and depressed feelings, when compared with the subjects taking placebo, but the numbers of study withdrawals did not differ by drug assignment. No significant difference in total cholesterol and glucose levels was observed by group assignment. Triglycerides increased significantly in the subjects assigned to propranolol (mean difference = +20 mg/dL; 95% CI of difference +1.5, +39). There was no difference in the responses to 21 quality of life items between the subjects assigned to propranolol and those assigned to placebo.\n This multicomponent lifestyle modification intervention was unable to promote persistent behavior changes and thus was inferior to propranolol therapy for the treatment for mild diastolic hypertension. Future research should focus on single modifiable factors to lower blood pressure.", "The Mediterranean Lifestyle Program was evaluated for its effects on multiple behavioral risk factors for coronary heart disease (CHD) among postmenopausal women with diabetes.\n Our purpose is to test a comprehensive lifestyle management intervention to reduce CHD risk in postmenopausal women with type 2 diabetes.\n Participants (N = 279) were randomized to usual care (UC) or Mediterranean Lifestyle Program, a lifestyle change intervention aimed at the behavioral risk factors (eating patterns, physical activity, stress management, and social support) affecting risk for CHD in postmenopausal women with type 2 diabetes.\n In original and intent-to-treat analyses, Mediterranean Lifestyle Program participants showed significantly greater improvement in dietary behaviors, physical activity, stress management, perceived support, and weight loss at 6 months compared to UC.\n This study demonstrated the effectiveness of the Mediterranean Lifestyle Program in improving self-care among women with type 2 diabetes, showed that postmenopausal women could make comprehensive lifestyle changes, and provided evidence that a program using social-cognitive strategies and peer support can be used to modify multiple lifestyle behaviors.", "Insulin resistance and hyperinsulinaemia are, in some prospective studies, linked to an increased cardiovascular risk, at least in men. We tested the hypothesis that hyperinsulinaemia may be reduced by non-pharmacological methods independently of other cardiovascular risk factors.\n In a non-pharmacological intervention study for 1 year three groups of subjects (hypertensives as well as normotensives) were selected after stratification for insulin level at baseline. Half of the hyperinsulinaemic subjects were randomly assigned to active intervention with physical exercise and dietary regulation (HI-A group), the other half were followed passively during the study period (HI-P group). Normo-insulinaemics and hypo(low)-insulinaemics also underwent active intervention (NI-A and LI-A groups, respectively).\n Primary health care in Sweden.\n During the 1-year follow-up subjects in the HI-A group reduced their weight, waist:hip ratio and systolic and diastolic blood pressure, as well as their low:high-density lipoprotein (LDL:HDL)-cholesterol ratio. Glucose levels before and during an oral glucose tolerance test did not change. However, plasma insulin and plasma-C-peptide decreased both in the fasting state and after 1 and 2 h of oral glucose tolerance testing. This decrease was independent of the previously mentioned reduction in weight, waist:hip ratio, blood pressure and LDL:HDL-cholesterol ratio. No reduction in insulin levels was seen in the HI-P, NI-A or LI-A groups, but in the HI-P group there was a slight decrease in fasting plasma-C-peptide levels. In the HI-A group dietary improvements were observed during the study period, with a reduction in energy intake, fat consumption and cholesterol intake. Fibre intake was increased. No major changes were seen in the HI-P group.\n We conclude that in hypertensive and normotensive subjects with hyperinsulinaemia insulin levels can be reduced by active non-pharmacological treatment for 1 year without altering glucose tolerance. This shows that insulin resistance may be lowered by non-pharmacological treatment, which may be of considerable importance, and not only for hypertensives.", "To evaluate the impact of a low-cost nutritional intervention in changing the lifestyle of adults.\n Randomised clinical trial.\n Primary health-care centre in São José do Rio Preto, São Paulo State, Brazil.\n We randomly assigned 104 adults (83 women and 21 men aged 30-65 years, body mass index 24-35 kg m(-2), non-diabetic) into two groups: nutrition counselling and control. Each subject in the intervention group received three individualised nutritional counselling sessions during the first 6 months aimed at increasing intakes of fruits, vegetables and olive oil, reducing saturated fat and improving physical activity. Body composition, biochemical indicators and lifestyle were assessed at baseline and at 6 months and 1 year in both groups.\n After 6 months of follow-up, body weight, waist circumference, diastolic blood pressure, fasting blood glucose, total and low-density lipoprotein cholesterol, total and saturated fat, and dietary energy and cholesterol levels showed a more significant decrease among subjects in the intervention group than in the control group (P < 0.05). Moreover, the intervention group showed significantly greater improvement in each intervention goal, such as reduced intake of saturated fat and increased intakes of fruits, vegetables, fibre and olive oil (P < 0.05). After 12 months of follow-up, most of the outcomes were maintained.\n The low-cost nutritional intervention programme improved serum lipids profile and weight control, and appeared to be feasible for use at a primary health-care centre in a developing country.", "Healthy lifestyle factors are associated with maintenance of erectile function in men.\n To determine the effect of weight loss and increased physical activity on erectile and endothelial functions in obese men.\n Randomized, single-blind trial of 110 obese men (body mass index > or =30) aged 35 to 55 years, without diabetes, hypertension, or hyperlipidemia, who had erectile dysfunction that was determined by having a score of 21 or less on the International Index of Erectile Function (IIEF). The study was conducted from October 2000 to October 2003 at a university hospital in Italy.\n The 55 men randomly assigned to the intervention group received detailed advice about how to achieve a loss of 10% or more in their total body weight by reducing caloric intake and increasing their level of physical activity. Men in the control group (n = 55) were given general information about healthy food choices and exercise.\n Erectile function score, levels of cholesterol and triglycerides, circulating levels of interleukin 6, interleukin 8, and C-reactive protein, and endothelial function as assessed by vascular responses to l-arginine.\n After 2 years, body mass index decreased more in the intervention group (from a mean [SD] of 36.9 [2.5] to 31.2 [2.1]) than in the control group (from 36.4 [2.3] to 35.7 [2.5]) (P<.001), as did serum concentrations of interleukin 6 (P =.03), and C-reactive protein (P =.02). The mean (SD) level of physical activity increased more in the intervention group (from 48 [10] to 195 [36] min/wk; P<.001) than in the control group (from 51 [9] to 84 [28] min/wk; P<.001). The mean (SD) IIEF score improved in the intervention group (from 13.9 [4.0] to 17 [5]; P<.001), but remained stable in the control group (from 13.5 [4.0] to 13.6 [4.1]; P =.89). Seventeen men in the intervention group and 3 in the control group (P =.001) reported an IIEF score of 22 or higher. In multivariate analyses, changes in body mass index (P =.02), physical activity (P =.02), and C-reactive protein (P =.03) were independently associated with changes in IIEF score.\n Lifestyle changes are associated with improvement in sexual function in about one third of obese men with erectile dysfunction at baseline.", "To examine the feasibility and efficacy of a multifactorial intervention programme directed towards hypercholesterolaemia, smoking, and diabetes mellitus in treated hypertensive patients after more than 3 years' follow-up and to describe the incidence of cardiovascular complications.\n Open, randomized, parallel-group study with allocation either to a comprehensive multiple risk factor modification programme or to usual care.\n Outpatient clinic in a city hospital.\n A total of 508 male patients with treated hypertension, aged 50-72 years, with at least one of the following: serum cholesterol > or = 6.5 mmol L-1, smoking or diabetes mellitus.\n Individually given advice and group meetings based on nutritional advice and behavioral treatment principles. Drug therapy could be instituted to achieve the treatment goals in the intervention group: serum total cholesterol below 6.0 mmol L-1, no smoking, and HbA1c below 6.0%. Diastolic blood pressure below 90 mmHg was the treatment goal in both groups.\n Serum cholesterol, HbA1c, diastolic blood pressure, smoking. Cardiovascular end-points were recorded.\n The net changes were (change intervention--change usual care): serum cholesterol -5.0% (95% confidence interval, -7.6 to -2.3%), 17.6% more stopped smoking (P = 0.04); diastolic blood pressure and HbA1c remained unchanged. The incidence of stroke was lower in the intervention group compared with the usual-care group: 2.0 and 6.7%, respectively (P = 0.017).\n The intervention programme was comparatively successful with regards to the effects on hypercholesterolaemia and smoking habits. An unexpected decrease in the stroke incidence was observed in the intervention group compared with the usual-care group.", "In Mexico, hypertension is a major cause of disability and death in the elderly, but the most effective way to promote behaviour change in old people is unknown. Low resource interventions that are effective in normal healthcare settings are urgently needed. We report the results of a randomized trial of nurse-provided health and lifestyle advice during home visits to elderly people with hypertension in Mexico City.\n Subjects were 718 people with hypertension aged > or =60 years, who were residents of Mexico City and were registered with the Family Medicine Clinics of the Mexican Institute of Social Security (IMSS). A randomized controlled trial was carried out in which the intervention group was offered nurse visits over 6 months with blood pressure checks and negotiated lifestyle changes. The control group continued to receive usual care.\n After 6 months, 36.5% of the intervention versus 6.8% of the control group had a blood pressure of <160/90 mmHg. The difference in the mean change in systolic blood pressure was 3.31 mmHg (P = 0.03, 95% CI : 6.32, 0.29) and the same difference in diastolic blood pressure was 3.67 mmHg (P = 0.00, 95% CI : 5.22, 2.12). Weight and sodium excretion fell more in the intervention group, but the difference was not significant.\n Nurse home visits are effective in reducing blood pressure in hypertensive patients aged > or =60 years.", "The purpose of this study was to evaluate the short-term effects of a low-intensity work-site heart disease risk reduction program using a matched pair design with work site as the unit of analysis.\n Twenty-six heterogeneous work sites with between 125 and 750 employees were matched on key organization characteristics and then randomly assigned to early or delayed intervention conditions. Early intervention consisted of an 18-month multifaceted program that featured an employee steering committee and a menu approach to conducting key intervention activities tailored to each site.\n Cross-sectional and cohort analyses produced consistent results. At the conclusion of the intervention, early and delayed intervention conditions did not differ on changes in smoking rates, dietary intake, or cholesterol levels. There was considerable variability in outcomes among work sites within each condition.\n Despite documented implementation of key intervention activities and organization-level changes in terms of perceived support for health promotion, this intervention did not produce short-term improvements beyond secular trends observed in control work sites. Research is needed to understand determinants of variability between work sites.", "The purpose of this study was to evaluate the feasibility and effectiveness of a community approach to hypertension control in both high risk and general populations in an agricultural district with limited medical and community resources. It was conducted in Yu-Chi district of Nan-Tou county in central Taiwan from 1993 to 1994. The study included blood pressure screening, follow-up, health education, village-based campaigns, and program evaluation after 6 months of intervention. Two villages each were randomly assigned to intervention and control groups. Intervention comprised visits by trained volunteers to measure blood pressure and body weight, and education related to hypertension. All residents 40 years of age and older were enrolled. A total of 471 residents from the intervention villages and 426 residents from the control villages completed the study. Overall, for the intervention and control groups, the knowledge and behavior related to hypertension improved significantly 6 months after the baseline survey. The improvement was greater in the subgroup of hypertensives in the intervention group than in the controls. The educational intervention also significantly improved the status of awareness, treatment, and the control of hypertension, and reduced blood pressure in the hypertensive subjects. We conclude that a hypertension control program that relies solely on limited community resources is feasible and effective.", "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.", "Altogether 86 patients with recently diagnosed NIDDM, aged 40-64 years were randomised after 3 months of basic education to intensified diet (Int. group, 21 men, 19 women) or conventional treatment groups (Conv. group, 28 men, 18 women). The aim was to examine whether an intensified diet education would result in a better metabolic control and greater reduction in cardiovascular risk factors than conventional treatment for obese patients with recently diagnosed type 2 diabetes mellitus. Furthermore, both groups were re-examined after a second year of observation period to find out the maintenance of the results after intervention. After basic education, Int. group participated in 12-months diet education, while Conv. group was treated in local health centres. During the intervention period, only Int. group showed further weight reduction. Only 20% of patients in Int. and 6% of patients in Conv. group had BMI < 27 kg/m2 at the end of the intervention, while 75% of patients in Int. and 52% of patients in Conv. group had achieved a good metabolic control (fasting blood glucose < 6.7 mmol/l; P = 0.005 between groups). Serum total cholesterol did not change significantly, but the changes in HDL-cholesterol, triglycerides and apolipoprotein B level were significant in Int. group only. The proposed acceptable values for serum lipids were achieved by 52 to 88% of patients without major differences between the two groups. During the second year of observation, weight gained in both groups and a deterioration was seen in metabolic control. Despite that a greater proportion of patients in the Int. group still was in good metabolic control (55.3% vs. 31.8%, P = 0.016), furthermore Int. group was receiving less frequently oral drugs for hyperglycaemia than Conv. group. No differences in serum lipids were observed between the groups after the observation period. HDL-cholesterol showed a persistent improvement in both groups.", "To assess the effects of lifestyle intervention on cardiovascular risk factors in general and especially on fibrinolysis.\n Randomized clinical study.\n A total of 186 subjects with impaired glucose tolerance and obesity.\n The intervention programme included a low-fat, high-fibre diet and regular physical exercise. Half of the participants (n = 93) took part in a one-month learning and training session using different behavioural modification techniques and conducted in a full-board wellness centre (intense intervention group). The other half (n = 93) was randomized a one-hour counselling session with a specially trained nurse (usual care group). Follow-up was carried out after 12 months.\n Body weight, oxygen consumption, plasminogen activator inhibitor type 1 (PAI-1) activity, tissue plasminogen activator (tPA) antigen, fibrinogen and fasting plasma insulin measured at the start of the programme and at follow-up after 1 year.\n The intense intervention group had a mean weight decline by 1 year of 5.4 kg compared to 0.5 kg in the usual care group. Oxygen consumption in the intense group increased 10% vs. a 1% decline in the usual care group. In the intense group, PAI-1 activity decreased 31% (-10.1 U mL(-1)), which was significantly more than in the usual care group (12%; -3.0 U mL(-1)). The corresponding reductions in tPA antigen were 14% (-1.65 microg L(-1)) and 6% (-0.69 microg L(-1)).\n The present randomized study shows that an intense lifestyle programme has sustained beneficial effects on fibrinolysis.", "Although nonpharmacologic interventions are widely recommended in the therapy of high blood pressure in older adults, surprisingly little data exist to confirm the efficacy of these interventions in older persons.\n We conducted a randomized, controlled clinical trial in persons aged 60 to 85 years with a diastolic blood pressure of 85 to 100 mm Hg. The experimental arm was a nonpharmacologic intervention combining weight reduction, sodium restriction, and increased physical activity. The nonpharmacologic intervention consisted of eight weekly group and two individual sessions during the intensive phase, followed by four monthly group sessions during the maintenance phase. The control group received no treatment during the study. Blood pressure was assessed by certified technicians (blinded to group assignment) using random zero sphygmomanometers.\n Of 56 participants randomized, 47 completed the entire 6-month trial (21 in the intervention group and 26 in the control group). Attendance at the intervention sessions was excellent. The intervention group lost more weight (-2.1 kg) over 6 months than the control group (+0.3 kg). Trends for decreasing 24-hour urine sodium excretion in both the intervention and control groups, with greater trend in the intervention group, were not statistically significant. The intervention group experienced more reduction in systolic and diastolic blood pressure than did the control group (mean differences between groups at 6 months, 4.2/4.9 mm Hg, respectively).\n Our data indicate that a nonpharmacologic intervention will lower systolic and diastolic blood pressure levels in older people with borderline or mild elevations of diastolic blood pressure.", "The authors examined the effects of a comprehensive lifestyle modification intervention on blood pressure (BP) and other cardiovascular risk factors in hypertensive patients. A total of 70 participants were randomly placed into either a lifestyle intervention or a control group. Four education classes and individual counseling sessions were held for the intervention group. Participants in the control group were provided with routine outpatient services and were asked to maintain their usual lifestyle. Data were gathered at baseline and at the end of 6 months. At the end of 6 months, BP, body weight, body mass index, waist circumference, and fasting lipids, apart from high-density lipoprotein cholesterol, significantly declined in the intervention group. Healthpromoting lifestyle scores of the intervention group had increased significantly compared to those of the control group. In conclusion, the results demonstrate the feasibility of comprehensive lifestyle modification and show its beneficial effects.", "The long-term effectiveness of multicomponent worksite health promotion programs targeting cardiovascular disease risk factors remains unclear in Japan. This study was conducted to evaluate the effectiveness of such a health promotion program consisting of a main program provided over 4 days and a follow-up program provided over 1 year.\n The subjects of this randomized controlled trial were male employees working for a building maintenance company in Japan. The intervention group (n = 152) and the control group (n = 150) consisted of employees having abnormal findings in at least one of the following items at baseline health examination: body mass index (BMI), systolic (SBP) or diastolic blood pressure, total cholesterol, HDL cholesterol, triglycerides, and fasting blood glucose. Evaluation was conducted at 18 months after the main program.\n BMI, SBP, total cholesterol, and triglycerides improved significantly in the intervention group compared with the control group (P < 0.05). When comparisons were limited to those who showed abnormality at baseline, BMI, total cholesterol, and triglycerides improved significantly in the intervention group (P < 0.05).\n The multicomponent health promotion program provided to employees was shown to be effective in improving obesity, high blood pressure, and hyperlipidemia when evaluated 18 months after the main intervention program.\n Copyright 2001 American Health Foundation and Elsevier Science.", "The Multiple Risk Factor Intervention Trial was a randomized primary prevention trial to test the effect of a multifactor intervention program on mortality from coronary heart disease (CHD) in 12,866 high-risk men aged 35 to 57 years. Men were randomly assigned either to a special intervention (SI) program consisting of stepped-care treatment for hypertension, counseling for cigarette smoking, and dietary advice for lowering blood cholesterol levels, or to their usual sources of health care in the community (UC). Over an average follow-up period of seven years, risk factor levels declined in both groups, but to a greater degree for the SI men. Mortality from CHD was 17.9 deaths per 1,000 in the SI group and 19.3 per 1,000 in the UC group, a statistically nonsignificant difference of 7.1% (90% confidence interval, -15% to 25). Total mortality rates were 41.2 per 1,000 (SI) and 40.4 per 1,000 (UC). Three possible explanations for these findings are considered: (1) the overall intervention program, under these circumstances, does not affect CHD mortality; (2) the intervention used does affect CHD mortality, but the benefit was not observed in this trial of seven years' average duration, with lower-than-expected mortality and with considerable risk factor change in the UC group; and (3) measures to reduce cigarette smoking and to lower blood cholesterol levels may have reduced CHD mortality within subgroups of the SI cohort, with a possibly unfavorable response to antihypertensive drug therapy in certain but not all hypertensive subjects. This last possibility was considered most likely, needs further investigation, and lends support to some preventive measures while requiring reassessment of others." ]

[ "11940128" ]

[ "Impact of a nurse-led counselling service on quality of life in patients with inflammatory bowel disease." ]

[ "Health related quality of life is impaired in patients suffering from inflammatory bowel disease. Although counselling directed towards physical and psychological morbidity is assumed to improve health related quality of life, this has never been demonstrated.\n Physical and psychological well-being were assessed using questionnaires administered to 100 out-patients in the United Kingdom suffering from inflammatory bowel disease, 50 subjects not suffering from inflammatory bowel disease and a disease control group comprising 28 patients with psoriatic arthritis. A specific nurse led counselling package was given to half the inflammatory bowel disease group and health related quality of life was assessed at baseline, 6 and 12 months.\n Inflammatory bowel disease and psoriatic arthritic patients had a range of physical disease activity, although none were severely ill during the course of the study. Medical therapy was similar in both groups throughout the duration of the trial. The mean Short Form 36 (SF-36) scores for mental health were low in inflammatory bowel disease patients; 62.9 +/- 9.1 (SD) in ulcerative colitis, 60 +/- 9.8 (SD) in Crohn's disease, compared with 72.4 +/- 7.2 (SD) in healthy controls (P < 0.05). Mean SF-36 scores for social function were also reduced in Crohn's disease patients; 68.4 +/- 10.1 (SD) in Crohn's disease, compared with 87 +/- 10.1 (SD) in healthy controls (P < 0.05). As expected, the mean SF-36 scores in psoriatic arthritic patients were significantly low 61.9 +/- 1.5 (SD) compared with 82.4 +/- 14 (SD) in healthy controls (P < 0.05). Crohn's disease patients were significantly more anxious than the other groups, mean HAD score was 10 +/- 3.7 (SD) in Crohn's disease patients and 6.86 +/- 3.5 (SD) in healthy volunteers (P < 0.05), although mean HAD scores for depression were similar in all groups. Maladaptive coping mechanisms were present in a significant proportion of Crohn's disease patients. At follow-up all aspects of psychological morbidity returned to the normal range in the Crohn's disease patients without significant change in the mean physical disease index.\n Health related quality of life can be improved over 6 months by provision of a nurse led counselling service but the effects are not sustained for 12 months." ]

[ "9480993", "9036320", "8765628", "14993550", "12673257", "9032045", "8885949", "10675427", "10545552", "10509497", "9255192", "9190553", "11098980" ]

[ "Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicenter study. The I-NO/PPHN Study Group.", "Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure.", "Inhaled nitric oxide in term infants with hypoxemic respiratory failure.", "A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term newborn infants with hypoxic respiratory failure.", "Inhaled nitric oxide in the treatment of moderate persistent pulmonary hypertension of the newborn: a randomized controlled, multicenter trial.", "Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group.", "Acute response to inhaled nitric oxide in newborns with respiratory failure and pulmonary hypertension.", "Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group.", "Randomized, controlled trial of low-dose inhaled nitric oxide in the treatment of term and near-term infants with respiratory failure and pulmonary hypertension.", "Early compared with delayed inhaled nitric oxide in moderately hypoxaemic neonates with respiratory failure: a randomised controlled trial. The Franco-Belgium Collaborative NO Trial Group.", "Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn.", "Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. The Neonatal Inhaled Nitric Oxide Study Group (NINOS).", "Inhaled nitric oxide reduces the need for extracorporeal membrane oxygenation in infants with persistent pulmonary hypertension of the newborn." ]

[ "To assess the dose-related effects of inhaled nitric oxide (I-NO) as a specific adjunct to early conventional therapy for term infants with persistent pulmonary hypertension (PPHN), with regard to neonatal outcome, oxygenation, and safety.\n Randomized, placebo-controlled, double-masked, dose-response, clinical trial at 25 tertiary centers from April 1994 to June 1996. The primary endpoint was the PPHN Major Sequelae Index ([MSI], including the incidence of death, extracorporeal membrane oxygenation (ECMO), neurologic injury, or bronchopulmonary dysplasia [BPD]). Patients required a fraction of inspired oxygen [FIO2] of 1.0, a mean airway pressure >/=10 cm H2O on a conventional ventilator, and echocardiographic evidence of PPHN. Exogenous surfactant, concomitant high-frequency ventilation, and lung hypoplasia were exclusion factors. Control (0 ppm) or nitric oxide (NO) (5, 20, or 80 ppm) treatments were administered until success or failure criteria were met. Due to slowing recruitment, the trial was stopped at N = 155 (320 planned).\n The baseline oxygenation index (OI) was 24 +/- 9 at 25 +/- 17 hours old (mean +/- SD). Efficacy results were similar among NO doses. By 30 minutes (no ventilator changes) the PaO2 for only the NO groups increased significantly from 64 +/- 39 to 109 +/- 78 Torr (pooled) and systemic arterial pressure remained unchanged. The baseline adjusted time-weighted OI was also significantly reduced in the NO groups (-5 +/- 8) for the first 24 hours of treatment. The MSI rate was 59% for the control and 50% for the NO doses (P = .36). The ECMO rate was 34% for control and 22% for the NO doses (P = .12). Elevated methemoglobin (>7%) and nitrogen dioxide (NO2) (>3 ppm) were observed only in the 80 ppm NO group, otherwise no adverse events could be attributed to I-NO, including BPD.\n For term infants with PPHN, early I-NO as the sole adjunct to conventional management produced an acute and sustained improvement in oxygenation for 24 hours without short-term side effects (5 and 20 ppm doses), and the suggestion that ECMO use may be reduced.", "Neonates with pulmonary hypertension have been treated with inhaled nitric oxide because of studies suggesting that it is a selective pulmonary vasodilator. We conducted a randomized, multicenter, controlled trial to determine whether inhaled nitric oxide would reduce mortality or the initiation of extracorporeal membrane oxygenation in infants with hypoxic respiratory failure.\n Infants born after a gestation of > or =34 weeks who were 14 days old or less, had no structural heart disease, and required assisted ventilation and whose oxygenation index was 25 or higher on two measurements were eligible for the study. The infants were randomly assigned to receive nitric oxide at a concentration of 20 ppm or 100 percent oxygen (as a control). Infants whose partial pressure of arterial oxygen (PaO2) increased by 20 mm Hg or less after 30 minutes were studied for a response to 80-ppm nitric oxide or control gas.\n The 121 infants in the control group and the 114 in the nitric oxide group had similar base-line clinical characteristics. Sixty-four percent of the control group and 46 percent of the nitric oxide group died within 120 days or were treated with extracorporeal membrane oxygenation (P=0.006). Seventeen percent of the control group and 14 percent of the nitric oxide group died (P not significant), but significantly fewer in the nitric oxide group received extracorporeal membrane oxygenation (39 percent vs. 54 percent, P=0.014). The nitric oxide group had significantly greater improvement in PaO2 (increase, 58.2+/-85.2 mm Hg, vs. 9.7+/-51.7 mm Hg in the controls; P<0.001) and in the oxygenation index (a decrease of 14.1+/-21.1, vs. an increase of 0.8+/-21.1 in the controls; P<0.001). The study gas was not discontinued in any infant because of toxicity.\n Nitric oxide therapy reduced the use of extracorporeal membrane oxygenation, but had no apparent effect on mortality in critically ill infants with hypoxic respiratory failure.", "To determine whether inhaled nitric oxide (NO) administered during conventional mechanical ventilation could produce improvements in oxygenation and reduce the incidence of meeting extracorporeal membrane oxygenation (ECMO) criteria in infants with hypoxemia.\n Prospective, randomized, controlled trial. Enrolled infants were assigned to conventional treatment with or without adjunctive inhaled NO. Control infants meeting failure criteria (partial pressure of arterial oxygen (PaO2)<80 mm Hg (10.7 kPa)) were allowed to cross over. Caregivers were not masked to group assignment.\n Neonatal intensive care units at the University of Alabama Hospital and the Children's Hospital of Alabama, October 1993 to May 1994.\n Newborn infants, both term and near-term, with PaO2 less than 100 mm Hg (13.3 kPa) who were receiving mechanical ventilation with 100% oxygen. Exclusion criteria included major congenital anomalies, diaphragmatic hernia, profound asphyxia, and significant bleeding.\n Inhaled NO was initiated in the NO group at a dose of 20 to 40 ppm and advanced stepwise to 80 ppm if PaO2 remained less than 100 mm Hg (13.3 kPa).\n Primary outcome variables were treatment failure and meeting of ECMO criteria before crossover. Improvement in oxygenation and ultimate use of ECMO or high-frequency oscillatory ventilation were secondary outcome variables.\n Seventeen neonates with hypoxemia were enrolled; 16 had echocardiographic evidence of pulmonary hypertension, and eight had extrapulmonary shunting. At 1 hour of treatment, two infants in the NO group responded with increases in PaO2 of more than 100 mm Hg (13.3 kPa); after crossover, two had increases in PaO2 of more than 10 mm Hg (1.3 kPa) and one control infant had an increase in PaO2 of more than 10 mm Hg (1.3 kPa). All control infants met failure criteria and crossed over to receive NO; two had increases in PaO2 of more than 10 mm Hg (1.3 kPa) with NO treatment. Despite initial responses, all subjects in both groups eventually met failure criteria. There were no differences between groups in primary outcome variables.\n Although inhaled NO produced a transient improvement in oxygenation in some infants, it did not reduce the incidence of meeting ECMO criteria in this population.", "Inhaled nitric oxide (iNO) reduces the use of extracorporeal membrane oxygenation (ECMO)/incidence of death in term and near-term neonates with severe hypoxic respiratory failure. We conducted a randomized, double masked, multicenter trial to determine whether administration of iNO earlier in respiratory failure results in additional reduction in the incidence of these outcomes.\n Neonates who were born at > or =34 weeks' gestation were enrolled when they required assisted ventilation and had an oxygenation index (OI) > or =15 and <25 on any 2 measurements in a 12-hour interval. Infants were randomized to early iNO or to simulated initiation of iNO (control). Infants who had an increase in OI to 25 or more were given iNO as standard therapy.\n The trial enrollment was halted after 75% of target sample size was reached because of decreasing availability of eligible patients. The 150 infants who were given early iNO and 149 control infants had similar baseline characteristics. Arterial oxygen tension increased by >20 mm Hg in 73% of early iNO and 37% of control infants after study gas initiation. Control infants received standard iNO and deteriorated to OI >40 more often than infants who were given early iNO. The incidence of death (early iNO, 6.7% vs control, 9.4%), ECMO (10.7% vs 12.1%), and their combined incidence (16.7% vs 19.5%) were similar in both groups.\n iNO improves oxygenation but does not reduce the incidence of ECMO/mortality when initiated at an OI of 15 to 25 compared with initiation at >25 in term and near-term neonates with respiratory failure.", "Inhaled nitric oxide (iNO) improves oxygenation and reduces the need for extracorporeal membrane oxygenation in infants with severe persistent pulmonary hypertension of the newborn (PPHN). The effectiveness of iNO in the treatment of moderate PPHN has not been adequately defined. We therefore conducted a randomized, prospective multicenter study to assess whether iNO in patients with moderate PPHN would improve arterial p(a)O(2), prevent progression to severe PPHN, and improve outcomes.\n Infants > or = 34 weeks gestation with moderate pulmonary hypertension (alveolar-arterial oxygen gradient (AaDO(2)) 500-599 Torr) were randomly assigned to continue standard medical therapy (control group) or standard medical therapy plus iNO (iNO group). For each patient in the iNO group, iNO concentration was increased in steps of 10-20 ppm every 30 minutes until there was no further improvement in arterial p(a)O(2). This concentration of iNO was then maintained while all other ventilatory support, including inspired oxygen concentration, was weaned according to a predefined protocol.\n In all, 27 of 40 control patients (58%) compared to six of 40 infants (15%) in the iNO group failed assigned therapy and developed severe PPHN (p<0.0005). Arterial p(a)O(2) improved from 112+/-48 to 133+/-100 (p=0.132) in control infants compared to an increase from 101+/-29 to 208+/-118 (p<0.0005) in iNO-treated patients. For the first 36 hours after study, entry AaDO(2) levels and ventilatory support were significantly lower in iNO-treated infants compared to control patients.\n In patients with moderate PPHN, treatment with iNO improves arterial p(a)O(2), reduces the amount of ventilatory support needed, and prevents progression to severe PPHN.", "Persistent pulmonary hypertension of the newborn causes systemic arterial hypoxemia because of increased pulmonary vascular resistance and right-to-left shunting of deoxygenated blood. Inhaled nitric oxide decreases pulmonary vascular resistance in newborns. We studied whether inhaled nitric oxide decreases severe hypoxemia in infants with persistent pulmonary hypertension.\n In a prospective, multicenter study, 58 full-term infants with severe hypoxemia and persistent pulmonary hypertension were randomly assigned to breathe either a control gas (nitrogen) or nitric oxide (80 parts per million), mixed with oxygen from a ventilator. If oxygenation increased after 20 minutes and systemic blood pressure did not decrease, the treatment was considered successful and was continued at lower concentrations. Otherwise, it was discontinued and alternative therapies, including extracorporeal membrane oxygenation, were used.\n Inhaled nitric oxide successfully doubled systemic oxygenation in 16 of 30 infants (53 percent), whereas conventional therapy without inhaled nitric oxide increased oxygenation in only 2 of 28 infants (7 percent). Long-term therapy with inhaled nitric oxide sustained systemic oxygenation in 75 percent of the infants who had initial improvement. Extracorporeal membrane oxygenation was required in 71 percent of the control group and 40 percent of the nitric oxide group (P=0.02). The number of deaths was similar in the two groups. Inhaled nitric oxide did not cause systemic hypotension or increase methemoglobin levels.\n Inhaled nitric oxide improves systemic oxygenation in infants with persistent pulmonary hypertension and may reduce the need for more invasive treatments.", "Systemic oxygenation is improved by inhaled nitric oxide therapy in some newborns with respiratory failure and pulmonary hypertension. Our results with inhaled nitric oxide were reviewed to determine factors associated with an acute improvement in systemic oxygenation.\n Newborns with oxygenation indices of 25 to 40 were prospectively randomized to receive conventional therapy with or without 20 ppm inhaled nitric oxide. All newborns with oxygenation indices greater than 40 were treated with inhaled nitric oxide. Hemodynamic, blood gas, and Doppler ultrasound measurements were performed before and after 30 to 60 minutes of observation or therapy. The severity of lung disease was classified by the chest radiograph as: (1) normal or focal disease; (2) moderate diffuse disease-diffuse lung disease with well-defined heart borders; or (3) severe diffuse disease-diffuse lung opacification with indistinct heart borders.\n Heart rate, blood pressure, and ductal diameters did not change. Blood gases and ductal shunting acutely improved only in patients treated with inhaled nitric oxide. Patients with normal lung fields or focal disease had the greatest degree of improvement in systemic oxygenation. Changes in oxygenation were not influenced by gestational age, baseline blood gases, the proportion of right-to-left ductal shunting, prior treatment with a surfactant, or the use of conventional or high-frequency jet ventilation. Collectively, blood gases and ductal shunting did not improve with inhaled nitric oxide in patients with lung hypoplasia or severe diffuse lung disease. Sustained improvement in oxygenation occurred in 87% of patients with oxygenation indices greater than 40 in whom oxygenation indices less than 40 acutely developed after exposure to nitric oxide, whereas 90% of patients in whom oxygenation indices less than 40 did not acutely develop were treated with extracorporeal membrane oxygenation or ultimately died.\n Inhaled nitric oxide acutely improves systemic oxygenation in many newborns with respiratory failure and pulmonary hypertension. The diagnosis and chest radiograph are helpful in identifying patients who will have favorable acute responses to therapy. In patients with severe hypoxemia, the need for invasive support with extracorporeal membrane oxygenation may be determined by an acute trial of inhaled nitric oxide.", "Inhaled nitric oxide improves gas exchange in neonates, but the efficacy of low-dose inhaled nitric oxide in reducing the need for extracorporeal membrane oxygenation has not been established.\n We conducted a clinical trial to determine whether low-dose inhaled nitric oxide would reduce the use of extracorporeal membrane oxygenation in neonates with pulmonary hypertension who were born after 34 weeks' gestation, were 4 days old or younger, required assisted ventilation, and had hypoxemic respiratory failure as defined by an oxygenation index of 25 or higher. The neonates who received nitric oxide were treated with 20 ppm for a maximum of 24 hours, followed by 5 ppm for no more than 96 hours. The primary end point of the study was the use of extracorporeal membrane oxygenation.\n Of 248 neonates enrolled, 126 were randomly assigned to the nitric oxide group and 122 to the control group. Extracorporeal membrane oxygenation was used in 78 neonates in the control group (64 percent) and in 48 neonates in the nitric oxide group (38 percent) (P=0.001). The 30-day mortality rate in the two groups was similar (8 percent in the control group and 7 percent in the nitric oxide group). Chronic lung disease developed less often in neonates treated with nitric oxide than in those in the control group (7 percent vs. 20 percent, P=0.02). The efficacy of nitric oxide was independent of the base-line oxygenation index and the primary pulmonary diagnosis.\n Inhaled nitric oxide reduces the extent to which extracorporeal membrane oxygenation is needed in neonates with hypoxemic respiratory failure and pulmonary hypertension.", "Recent reports indicate that inhaled nitric oxide (iNO) causes selective pulmonary vasodilation, increases arterial oxygen tension, and may decrease the use of extracorporeal membrane oxygenation (ECMO) in infants with persistent pulmonary hypertension of the newborn (PPHN). Despite these reports, the optimal dose and timing of iNO administration in PPHN remains unclear.\n To test the hypotheses that in PPHN 1) iNO at 2 parts per million (ppm) is effective at acutely increasing oxygenation as measured by oxygenation index (OI); 2) early use of 2 ppm of iNO is more effective than control (0 ppm) in preventing clinical deterioration and need for iNO at 20 ppm; and 3) for those infants who fail the initial treatment protocol (0 or 2 ppm) iNO at 20 ppm is effective at acutely decreasing OI.\n A randomized, controlled trial of iNO in 3 nurseries in a single metropolitan area. Thirty-eight children, average gestational age of 37.3 weeks and average age <1 day were enrolled. Thirty-five of 38 infants had echocardiographic evidence of pulmonary hypertension. On enrollment, median OI in the control group, iNO at 0 ppm, (n = 23) was 33.1, compared with 36.9 in the 2-ppm iNO group (n = 15).\n Initial treatment with iNO at 2 ppm for an average of 1 hour was not associated with a significant decrease in OI. Twenty of 23 (87%) control patients and 14 of 15 (92%) of the low-dose iNO group demonstrated clinical deterioration and were treated with iNO at 20 ppm. In the control group, treatment with iNO at 20 ppm decreased the median OI from 42.6 to 23.8, whereas in the 2-ppm iNO group with a change in iNO from 2 to 20 ppm, the median OI did not change (42.6 to 42.0). Five of 15 patients in the low-dose nitric oxide group required ECMO and 2 died, compared with 7 of 23 requiring ECMO and 5 deaths in the control group.\n In infants with PPHN, iNO 1): at 2 ppm does not acutely improve oxygenation or prevent clinical deterioration, but does attenuate the rate of clinical deterioration; and 2) at 20 ppm acutely improves oxygenation in infants initially treated with 0 ppm, but not in infants previously treated with iNO at 2 ppm. Initial treatment with a subtherapeutic dose of iNO may diminish the clinical response to 20 ppm of iNO and have adverse clinical sequelae.", "Inhaled nitric oxide improves oxygenation in severely hypoxaemic term neonates, which lessens the need for extracorporeal-membrane oxygenation. Improvement in other relevant outcomes remains unknown, and safety of inhaled nitric oxide is uncertain in preterm neonates. We did a randomised controlled trial to assess use of inhaled nitric oxide in preterm and near-term neonates.\n We randomly assigned 204 preterm (< 33 weeks) and near-term (> or = 33 weeks) neonates with oxygenation indices from 12.5 to 30.0 and 15 to 40, respectively, 10 parts per million (ppm) inhaled nitric oxide (n=105) or control ventilation therapy without nitric oxide (n=99). The primary endpoint was the oxygenation index at 2 h. Analysis was done by intention to treat.\n 12 neonates were excluded, leaving 97 (45 preterm) in the nitric-oxide group and 95 (40 preterm) in the control group. The decline in oxygenation index at 2 h was greater in the nitric-oxide group than in the control group (median 6.2 (IQR 8.4)) [corrected] vs -2.9 [12.4], p=0.005), but was significant only in near-term neonates (p=0.03). Survivors assigned nitric oxide spent fewer days on mechanical ventilation and in the neonatal intensive-care unit, but this was also significant only in near-term neonates (6 [3] vs 7 [3] days, p=0.05, and 9 [6] vs 12 [9] days, p=0.02, respectively).\n Low-dose inhaled nitric oxide early in the course of neonatal respiratory failure improves oxygenation and shortens duration of mechanical ventilation and the length of stay in intensive care. Inhaled nitric oxide was not, however, significantly beneficial in preterm neonates.", "Although inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in newborn infants with persistent pulmonary hypertension, its effects are variable. We hypothesized (1) that the response to iNO therapy is dependent on the primary disease associated with persistent pulmonary hypertension of the newborn (PPHN) and (2) that the combination of high-frequency oscillatory ventilation (HFOV) with iNO would be efficacious in patients for whom either therapy alone had failed.\n To determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were stratified by predominant disease category: respiratory distress syndrome (n = 70), meconium aspiration syndrome (n = 58), idiopathic PPHN or pulmonary hypoplasia (excluding congenital diaphragmatic hernia) (\"other\": n = 43), and congenital diaphragmatic hernia (n = 34); they were then randomly assigned to treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment failure (partial pressure of arterial oxygen [PaO2] < 60 mm Hg) resulted in crossover to the alternative treatment; treatment failure after crossover led to combination treatment with HFOV plus iNO. Treatment response with the assigned therapy was defined as sustained PaO2 of 60 mm Hg or greater.\n Baseline oxygenation index and PaO2 were 48 +/- 2 and 41 +/- 1 mm Hg, respectively, during treatment with conventional ventilation. Ninety-eight patients were randomly assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three patients (26%) recovered with the initially assigned therapy without crossover (30 with iNO [28%] and 23 with HFOV [23%]; p = 0.33). Within this group, survival was 100% and there were no differences in days of mechanical ventilation, air leak, or supplemental oxygen requirement at 28 days. Of patients whose initial treatment failed, crossover treatment with the alternate therapy was successful in 21% and 14% for iNO and HFOV, respectively (p = not significant). Of 125 patients in whom both treatment strategies failed, 32% responded to combination treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either treatment alone or combination therapy. By disease category, response rates for HFOV plus iNO in the group with respiratory syndrome and the group with meconium aspiration syndrome were better than for HFOV alone or iNO with conventional ventilation (p < 0.05). Marked differences in outcomes were noted among centers (percent death or treatment with extracorporeal membrane oxygenation = 29% to 75%).\n We conclude that treatment with HFOV plus iNO is often more successful than treatment with HFOV or iNO alone in severe PPHN. Differences in responses are partly related to the specific disease associated with PPHN.", "We designed and conducted a randomized, double-masked, controlled multicenter study to determine whether inhaled nitric oxide (INO) in term and near-term infants with congenital diaphragmatic hernia (CDH) would reduce the occurrence of death and/or the initiation of extracorporeal membrane oxygenation (ECMO).\n Infants of 34 weeks gestation or more, <14 days of age with CDH, without known structural heart disease, requiring assisted ventilation for hypoxemic respiratory failure with two oxygenation indices (OIs) of 25 or more at least 15 minutes apart, were eligible for this trial. Infants were centrally randomized and then received masked treatment with 20 ppm NO or 100% oxygen as control. Infants with less than a full response to 20 ppm NO (increase in PaO2 > 20 Torr) after 30 minutes were evaluated at 80 ppm NO/control study gas.\n The 28 control and 25 treated infants enrolled by the 13 participating centers were not significantly different at randomization for any of the measured variables including prerandomization therapies and initial OIs (45.8 +/- 16.3 for controls, 44.5 +/- 14.5 for INO). Death at <120 days of age or the need for ECMO occurred in 82% of control infants compared with 96% of INO infants (ns). Death occurred in 43% of controls and 48% of the INO group (ns), and ECMO treatment was used for 54% of control and 80% of INO-treated infants. There was no significant improvement in PaO2 (delta PaO2 7.8 +/- 19.8 vs 1.1 +/- 7.6 Torr, ns) nor significant reduction in OI (-2.7 +/- 23.4 vs 4.0 +/- 14.8, ns) associated with INO treatment. Mean peak nitrogen dioxide (NO2) concentration was 1.9 +/- 1.3 ppm and the mean peak methemoglobin was 1.6 +/- 0.8 mg/dL. No infant had study gas discontinued for toxicity. There were no differences between the control and INO groups for the occurrence of intracranial hemorrhage, specific grades of intracranial hemorrhage, periventricular leukomalacia, brain infarction, and pulmonary or gastrointestinal hemorrhages.\n Although the immediate short-term improvements in oxygenation seen in some treated infants may be of benefit in stabilizing responding infants for transport and initiation of ECMO, we conclude that for term and near-term infants with CDH and hypoxemic respiratory failure unresponsive to conventional therapy, inhaled NO therapy as used in this trial did not reduce the need for ECMO or death.", "We previously reported improved oxygenation, but no change, in rates of extracorporeal membrane oxygenation (ECMO) use or death among infants with persistent pulmonary hypertension of the newborn who received inhaled nitric oxide (NO) with conventional ventilation, irrespective of lung disease. The goal of our study was to determine whether treatment with inhaled NO improves oxygenation and clinical outcomes in infants with persistent pulmonary hypertension of the newborn and associated lung disease who are ventilated with high-frequency oscillatory ventilation (HFOV).\n Single-center, prospective, randomized, controlled trial.\n Newborn intensive care unit of a tertiary care teaching hospital.\n We studied infants with a gestational age of > or =34 wks who were receiving mechanical ventilatory support and had echocardiographic and clinical evidence of pulmonary hypertension and hypoxemia (PaO2 < or =100 mm Hg on FIO2 = 1.0), despite optimal medical management Infants with congenital heart disease, diaphragmatic hernia, or other major anomalies were excluded.\n The treatment group received inhaled NO, whereas the control group did not. Adjunct therapies and ECMO criteria were the same in the two groups of patients. Investigators and clinicians were not masked as to treatment assignment, and no crossover of patients was permitted.\n Primary outcome variables were mortality and use of ECMO. Secondary outcomes included change in oxygenation and duration of mechanical ventilatory support and supplemental oxygen therapy. Forty-two patients were enrolled. Baseline oxygenation and clinical characteristics were similar in the two groups of patients. Infants in the inhaled NO group (n = 21) had improved measures of oxygenation at 15 mins and 1 hr after enrollment compared with infants in the control group (n = 20). Fewer infants in the inhaled NO group compared with the control group were treated with ECMO (14% vs. 55%, respectively; p = .007). Mortality did not differ with treatment assignment.\n Among infants ventilated by HFOV, those receiving inhaled NO had a reduced need for ECMO. We speculate that HFOV enhances the effectiveness of inhaled NO treatment in infants with persistent pulmonary hypertension of the newborn and associated lung disease." ]

[ "14516308" ]

[ "A traditional healers' training model in rural Nepal: strengthening their roles in community health." ]

[ "In this paper, we evaluated a western medical training model for traditional healers (THs) in rural Nepal. We used semi-structured interviews to compare 48 trainees with 30 randomly selected untrained THs, 1 year after the training was completed. We asked them about their knowledge of the causes, prevention and treatment of common illnesses and HIV/AIDS, and their relationship with government health workers (GHWs) in the area. Nine GHWs were also interviewed about their perceptions of THs. We found that trained THs had a better knowledge of allopathic medicine, practised modern treatment using first aid kits, and were more likely to refer patients to GHWs. They also improved their relationships with the GHWs. Up-scaling this model is a challenge for improving community health care in Nepal in the future." ]

[ "10326116", "2404072", "2201320", "11049793", "12423984" ]

[ "A double-'blind' placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico.", "A controlled trial of bovine dialyzable leukocyte extract for cryptosporidiosis in patients with AIDS.", "Treatment with bovine hyperimmune colostrum of cryptosporidial diarrhea in AIDS patients.", "Paromomycin: no more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trial Group.", "Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial." ]

[ "Sixty-six patients with human immunodeficiency virus infection and diarrhoea caused by Cryptosporidium parvum were enrolled in a double-'blind' placebo-controlled study to evaluate the safety and efficacy of nitazoxanide in the treatment of cryptosporidiosis related to the acquired immune deficiency syndrome. Patients were randomly assigned to one of 3 treatment groups and received either 500 mg twice daily of nitazoxanide, 1000 mg twice daily of nitazoxanide, or placebo orally for 14 d; the patients on nitazoxanide then crossed over to placebo while the placebo patients crossed over to nitazoxanide therapy at either the high or low dose depending on their randomization. Three post-treatment faecal examinations were conducted on days 15, 22 and 29 following initiation of treatment: patients were considered 'cured' if none revealed any C. parvum oocysts. Both doses of nitazoxanide produced parasitological cure rates superior to the placebo responses (12/19 [63%, P = 0.016] for patients receiving 1 g/d and 10/15 [67%, P = 0.013] for those receiving 2 g/d). Parasitological cure was correlated with the complete resolution of the diarrhoeal syndrome in 19 of the 22 treated patients who were considered parasitologically cured (86%). Both doses of nitazoxanide were well tolerated by the patients.", "Cryptosporidial infection causes severe diarrheal disease in patients with AIDS. Fourteen patients with AIDS and symptomatic cryptosporidiosis were treated with a specific bovine dialyzable leukocyte extract (immune DLE) prepared from lymph node lymphocytes of calves immunized with cryptosporidia or a nonspecific (nonimmune) DLE prepared from nonimmunized calves. Six of 7 patients given immune DLE gained weight and had a decrease in bowel movement frequency, with eradication of oocysts from stool in 5 patients. Six of 7 patients given nonimmune DLE showed no decrease in bowel movement and 4, no clearing of oocytes from stool; 5 continued to lose weight. Subsequently, 5 of these 7 were treated with immune DLE; 4 had a decrease in bowel movement frequency and significant weight gain, with eradication of oocytes from stool in 2 patients. Immune DLE produces sustained symptomatic improvement in patients with AIDS and active cryptosporidiosis, but lack of an appropriate cryptosporidial antigen allows only postulation that an augmentation of cellular immunity to Cryptosporidium parvum induced by immune DLE resulted in the microbiologic and clinical improvement observed.", "Cryptosporidium parvum may cause severe, debilitating diarrhea in patients with AIDS. Recent anecdotal reports have suggested that hyperimmune bovine colostrum may be effective. We conducted a double-blind, controlled pilot study of hyperimmune bovine colostrum for diarrhea due to cryptosporidiosis in five AIDS patients. The patients were randomized to receive either hyperimmune or control colostrum by continuous nasogastric infusion for 10 days. All stools were collected, graded, and weighed, and the concentration of oocysts excreted was determined daily. One of the three patients treated with hyperimmune colostrum had a reduction in diarrhea and in the concentration of oocysts excreted. A second treated patient had a modest decrease in the concentration of oocysts excreted. Two patients who received control colostrum also had decreases in the volume of diarrhea but no change in the concentration of oocysts excreted. We conclude that hyperimmune colostrum with high titers of specific anti-Cryptosporidium antibody could be effective in treating patients with cryptosporidiosis. However, more studies of cow colostral immunoglobulin need to be performed so that the efficacy of this treatment can be assessed more thoroughly.", "To evaluate the efficacy of paromomycin for the treatment of symptomatic cryptosporidial enteritis in human immunodeficiency virus-infected adults, we conducted a prospective, randomized, double-blind, placebo-controlled trial before the widespread introduction of highly active antiretroviral therapy (HAART). Seven units under the auspices of the AIDS Clinical Trials Group enrolled 35 adults with CD4 cell counts of < or = 150/mm(3). Initially, 17 patients received paromomycin (500 mg 4 times daily) and 18 received matching placebo for 21 days. Then all patients received paromomycin (500 mg q.i.d.) for an additional 21 days. Clinical definitions of response were measured by an average number of bowel movements per day in association with concurrent need for antidiarrheal agents that was lower than that before study entry. There was no treatment response during the placebo-controlled phase of the study according to protocol-defined criteria (P=.88). Three paromomycin recipients (17.6%) versus 2 placebo recipients (14.3%) responded completely. Rates of combined partial and complete responses in the paromomycin arm (8 out of 17, 47.1%) and the placebo arm (5 out of 14, 35.7%) of the study were also similar (P=.72). The clinical course of cryptosporidiosis was quite variable. Paromomycin was not shown to be more effective than placebo for the treatment of symptomatic cryptosporidial enteritis. However, inadequate statistical power prevents definitive rejection of the usefulness of paromomycin as therapy for this infection.", "Cryptosporidiosis in children in developing countries causes persistent diarrhoea and malnutrition and is associated with increased mortality, but there is no effective treatment. We aimed to assess the effect of nitazoxanide-a new broad-spectrum antiparasitic drug-on morbidity and mortality in Zambian children with diarrhoea due to Cryptosporidium parvum.\n Children with cryptosporidial diarrhoea who were admitted to the University Teaching Hospital, Lusaka, Zambia, between November, 2000, and July, 2001, and whose parents consented to their having an HIV test were randomly assigned nitazoxanide (100 mg twice daily orally for 3 days) or placebo. The primary endpoint was clinical response on day 7 after the start of treatment. Secondary endpoints included parasitological response by day 10 and mortality at day 8. Analysis was by intention to treat, with exclusion of patients subsequently found to be negative for C parvum or co-infected at baseline. The trial was stratified by HIV serology.\n 50 HIV-seropositive and 50 HIV-seronegative children were recruited for the study, four of whom were subsequently excluded. In HIV-seronegative children, diarrhoea resolved in 14 (56%) of 25 receiving nitazoxanide and 5 (23%) of 22 receiving placebo (difference 33%, 95% CI 7-59; p=0.037). C parvum was eradicated from stool in 13 (52%) of 25 receiving nitazoxanide and three (14%) of 22 receiving placebo (38%, 95% CI 14-63; p=0.007). Four children (18%) of 22 in the placebo group had died by day 8, compared with none of 25 in the nitazoxanide group (-18%, -34 to 2; p=0.041). HIV-seropositive children did not benefit from nitazoxanide. Nitazoxanide was not significantly associated with adverse events in either stratum.\n A 3-day course of nitazoxanide significantly improved the resolution of diarrhoea, parasitological eradication, and mortality in HIV-seronegative, but not HIV-seropositive, children." ]

[ "9620192" ]

[ "Continuous passive motion following metacarpophalangeal joint arthroplasty." ]

[ "To determine whether a postoperative rehabilitation protocol incorporating continuous passive motion would increase the total range of motion obtained 6 months following silicone interposition arthroplasty of the metacarpophalangeal joints in patients with rheumatoid arthritis, a prospective trial randomizing patients to receive either continuous passive motion or the standard dynamic splint protocol (modified Madden protocol) was undertaken. Fifteen hands (60 joints) were treated with the modified Madden protocol and 10 hands (40 joints) had continuous passive motion. The mean 6-month postoperative range of motion was 7 degrees in the modified Madden cohort compared with 39 degrees in the continuous passive motion cohort, representing an improvement of 22 degrees in the modified Madden cohort compared with an improvement of only 5 degrees in the continuous passive motion cohort. Residual ulnar deviation 8 degrees vs 12 degrees and grip strength (2.3 kgf v 3.7 kgf) were both lower in the continuous passive motion cohort. Incorporation of the continuous passive motion machine in the postoperative rehabilitation protocol does not offer sufficient advantages to justify the added costs." ]

[ "11868136", "17157557", "10194151", "17552379", "15258478", "9231954", "17513285", "16565867", "15716221", "16564210" ]

[ "Improving compliance with nasal CPAP and vigilance in older adults with OAHS.", "A multicentre trial of education strategies at CPAP induction in the treatment of severe sleep apnoea-hypopnoea syndrome.", "Can intensive support improve continuous positive airway pressure use in patients with the sleep apnea/hypopnea syndrome?", "Increased adherence to CPAP with a group cognitive behavioral treatment intervention: a randomized trial.", "A pilot trial of a telecommunications system in sleep apnea management.", "Compliance with nasal CPAP can be improved by simple interventions.", "Pilot randomized trial of the effect of wireless telemonitoring on compliance and treatment efficacy in obstructive sleep apnea.", "The role of telemedicine in CPAP compliance for patients with obstructive sleep apnea syndrome.", "CPAP compliance: video education may help!", "Simple interventions improve re-attendance when treating the sleep apnoea syndrome." ]

[ "The present study examined the efficacy of a cognitive-behavioral intervention at improving compliance with CPAP and vigilance in older adults with obstructive sleep apnea/hypopnea syndrome (OSAHS). Participants included 12 subjects who were randomized into one of two groups controlling for age, education, disease severity, and vigilance. The experimental group received two 45-min sessions designed to educate subjects on the consequences of OSAHS and the efficacy of CPAP. The control group received the same extent of therapist contact but did not receive information on OSAHS or CPAP. All subjects were administered a test of vigilance both before and after the study. Compliance data were collected using CPAP devices with internal microprocessors at were read at 1, 4, and 12 weeks after treatment initiation. The results showed that the experimental condition did not enhance compliance after 1 week of treatment but did so by the 12-week follow-up. Subjects in the experimental condition had a run time of 3.2-h per night longer than did those in the control group. Those using CPAP more regularly at 12 weeks also showed greater improvement on vigilance at follow-up. Performance on vigilance testing before the introduction of CPAP was predictive of CPAP use at 12 weeks. In conclusion, a modest cognitive-behavioral intervention may substantially increase CPAP use and vigilance in older adults.", "Compliance with continuous positive airway pressure (CPAP) treatment in obstructive sleep apnoea syndrome (OSAS) may be difficult. Patient education is important but strategies and their outcomes are not clear.\n We studied the effects of four education strategies on compliance and quality of life changes with CPAP treatment in seven centres in the French ANTADIR homecare network. Patients received from prescribers either a simple oral explanation (SP) or an oral and written explanation (RP) of CPAP use. In addition, they received from homecare technicians either a single home visit (SH) at CPAP onset or repeated home visits at CPAP onset and at 1 week, 1 month and 3 months after (RH). Compliance and quality of life were evaluated at CPAP onset, and at 3, 6 and 12 months after initiation of treatment.\n One hundred twelve patients with severe OSAS (mean age 58+/-11 year, apnoea-hypopnoea index 58+/-25/h) were allocated randomly to groups (SP+SH; SP+RH; RP+SH; RP+RH) with no initial differences. Quality of life, evaluated by the generic SF-36 questionnaire, improved in the combined emotional domains. Compliance was over 5h in all four education groups. These effects were sustained over 12 months and were not different between the four groups. We conclude that standard education strategies for CPAP induction in France are sufficient for good compliance and improved quality of life with CPAP. Education with reinforced input should be focussed on identified subgroups prone to problems.", "Continuous positive airway pressure (CPAP) therapy is widely prescribed for patients with the sleep apnea/hypopnea syndrome (SAHS), but the use of CPAP for such patients is disappointingly low. We postulated that providing intensive educational programs and nursing support to SAHS patients might improve CPAP use and outcomes. We also examined the hypothesis that CPAP use would be greater among patients who had initiated their own referral than among those asked to seek help by a partner. We randomized 80 consecutive, new patients with SAHS to receive either usual support or additional nursing input including CPAP education at home and involving their partners, a 3-night trial of CPAP in our institution's sleep center, and additional home visits once they had begun CPAP. The primary outcome variable was objective CPAP use; symptoms, mood, and cognitive function were also assessed after 6 mo. CPAP use over 6 mo was greater (p = 0.003) among patients receiving intensive than among those receiving standard support (5.4 +/- 0.3 versus 3.9 +/- 0. 4 h/night [mean +/- SEM]), with greater improvements (p < 0.05) in SAHS symptoms, mood, and reaction time in the intensively supported group. CPAP use was greater (p = 0.002) among patients who initiated their own referrals. CPAP use and outcomes of therapy can be improved by provision of a nurse-led intensive CPAP education and support program. CPAP use is lower among patients whose partners ask them to seek treatment.", "To improve adherence to continuous positive airway pressure (CPAP) treatment in participants with obstructive sleep apnea (OSA) using a cognitive behavioral therapy (CBT) intervention.\n A randomized controlled trial.\n A major teaching hospital in Sydney (2005).\n One hundred individuals (96 men), ranging in age from 32 to 81 years, diagnosed with OSA.\n Two 1-hour CBT interventions (including a video of real CPAP users) plus treatment as usual (mask fitting and information) or treatment as usual only.\n Hours of CPAP usage was assessed at 7 nights and 28 nights. Adherence was defined as usage at least 4 hours per night. Questionnaires measuring self-efficacy, social support, and expectancy (mediators of adherence) were given after intervention or after usual treatment. A higher adherence to CPAP therapy was found in the CBT group (2.9 hours difference) relative to treatment as usual (P < 0.001) at 28 days. Only 4 participants in the CBT group did not initiate treatments after their titration study, compared with 15 in the treatment as usual group (P < 0.02). The CBT group had significantly higher scores for self-efficacy (P < 0.001) and social support P < 0.008) but not for expectancy.\n The CBT intervention resulted in both increased adherence and \"uptake\" of CPAP and therefore would be expected to reduce the social, economic, and health-related consequences of untreated OSA.", "Continuous positive airway pressure (CPAP) is an effective therapy for obstructive sleep apnea syndrome (OSAS), although many patients have difficulty adhering to this therapy. The purpose of this study was to investigate the effectiveness of totally automated telephone technology in improving adherence to prescribed CPAP therapy.\n This pilot study was a randomized clinical trial in 30 patients being started on CPAP therapy for OSAS. Patients were randomly assigned to use of a computer telephone system designed to improve CPAP adherence (telephone-linked communications for CPAP [TLC-CPAP]) in addition to usual care (n = 15) or to usual care alone (n = 15) for a period of 2 months. TLC-CPAP is a computer-based system that monitors patients' self-reported behavior and provides education and reinforcement through a structured dialogue.\n A sleep symptoms checklist and the Functional Outcomes of Sleep Questionnaire were administered at study entry and at 2-month follow up. Hours of CPAP use at effective mask pressure were measured by the CPAP device, stored in its memory, and retrieved at the 2-month visit.\n At 2 months, patients randomized to TLC-CPAP had fewer reported sleep-related symptoms (9.4 vs. 13.4, P = 0.047) than those receiving usual care. The average nightly CPAP use in the TLC-CPAP group was 4.4 hours compared with 2.9 hours (P = 0.076) in the usual-care group.\n This pilot study suggests that patients with OSAS started on CPAP and a concurrently administered automated education and counseling system had better CPAP adherence and better control of OSAS symptoms.", "Effectiveness of continuous positive airway pressure (CPAP) as a treatment of obstructive sleep apnea can be limited by poor compliance, but little is known about how to improve compliance. We performed a randomized, controlled clinical trial among 33 subjects of two interventions to improve compliance. One group of subjects received weekly phone calls to uncover any problems and encourage use, another received written information about sleep apnea and the importance of regular CPAP use, and a third served as control subjects. We found that intervention improved CPAP compliance (p = 0.059) and that the effect was particularly strong when intervention occurred during the first month of CPAP treatment (p = 0.004). Although the sample size did not allow definitive investigation of other explanatory variables, subjects with lower levels of education or those with relatives who used CPAP may have benefited from intervention more than other subjects. We conclude that simple, inexpensive efforts to improve compliance with CPAP can be effective, especially when applied at the start of CPAP treatment, but optimal intervention may vary with certain patient characteristics.", "Obstructive sleep apnea (OSA) is a prevalent and serious medical condition characterized by repeated complete or partial obstructions of the upper airway during sleep and is prevalent in 2% to 4% of working middle-aged adults. Nasal continuous positive airway pressure (CPAP) is the gold-standard treatment for OSA. Because compliance rates with CPAP therapy are disappointingly low, effective interventions are needed to improve CPAP compliance among patients diagnosed with OSA.\n The aim was to determine whether wireless telemonitoring of CPAP compliance and efficacy data, compared to usual clinical care, results in higher CPAP compliance and improved OSA outcomes.\n 45 patients newly diagnosed with OSA were randomized to either telemonitored clinical care or usual clinical care and were followed for their first 2 months of treatment with CPAP therapy. CPAP therapists were not blinded to the participants' treatment group.\n 20 participants in each group received the designated intervention. Patients randomized to telemonitored clinical care used CPAP an average of 4.1 +/- 1.8 hours per night, while the usual clinical care patients averaged 2.8 +/- 2.2 hours per night (P = .07). Telemonitored patients used CPAP on 78% +/- 22% of the possible nights, while usual care patients used CPAP on 60% +/- 32% of the nights (P = .07). No statistically significant differences between the groups were found on measures of CPAP efficacy, including measures of mask leak and the Apnea-Hypopnea Index. Patients in the telemonitored group rated their likelihood to continue using CPAP significantly higher than the patients in the usual care group. Patients in both groups were highly satisfied with the care they received and rated themselves as \"not concerned\" that their CPAP data were being wirelessly monitored.\n Telemonitoring of CPAP compliance and efficacy data and rapid use of those data by the clinical sleep team to guide the collaborative (ie, patient and provider) management of CPAP treatment is as effective as usual care in improving compliance rates and outcomes in new CPAP users. This study was designed as a pilot-larger, well-powered studies are necessary to fully evaluate the clinical and economic efficacy of telemonitoring for this population.", "The objective of this study was to compare continuous positive airway pressure (CPAP) use, functional status, and client satisfaction in obstructive sleep apnea syndrome (OSAS) patients randomized to either telemedicine support or traditional care. In our university-affiliated sleep disorders center, patients with OSAS who were initiating CPAP therapy were randomized to receive telemedicine support vs traditional follow-up care for 30 days. The telemedicine group received a \"Health Buddy\" computer that provided daily Internet-based informational support and feedback for problems experienced with CPAP use. At 30 days, there were no significant differences in the hours of CPAP use between groups receiving traditional care (M = 4.22, SD+/-2.05) and telemedicine support (M = 4.29, SD+/-2.15), p = 0.87, or in the proportion of nights with CPAP use between the traditional (M = 50%+/-33.8) and telemedicine groups (M = 47%+/-34.2), p=0.61. No significant differences were found between groups in functional status (M = 2.27+/-4.56 vs M = 2.03+/-3.88, respectively, p = 0.76) or client satisfaction (M = 28.0+/-3.51 vs M = 28.5+/-3.05, p = 0.43). Patients in the telemedicine and traditional groups had similar CPAP use, functional status, and client satisfaction. The data suggest that telemedicine support as provided by our model compares favorably with traditional care. As a provider-extender, telemedicine support for patients initiating use of CPAP may allow for greater practice efficiency while maintaining quality of care.", "CPAP remains the treatment of choice for Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS), but compliance with CPAP is poor. Of many interventions tried to improve CPAP compliance, only education and humidification have been shown to be of benefit. Our purpose was to develop and pilot test a video to enhance patient understanding of obstructive sleep apnea and of the purpose, logistics, and benefits of CPAP use in patients newly diagnosed with OSAHS. A patient's CPAP compliance in the first few weeks after starting its use is predictive of long-term compliance with CPAP treatment. It is imperative that patients grasp at the outset both the severity of OSAHS and the effectiveness of CPAP therapy.\n An educational video script was written based on recommendations for patient educational video materials and covering identified misconceptions about OSAHS and perceived barriers to CPAP use. The videotape is 15 min in length and features two middle-aged males, one African-American and one Euro-American, discussing OSAHS and CPAP in a factory break room.\n In a randomized two-group design with a control group, patients with newly diagnosed OSAHS, and who viewed the CPAP educational video on their first clinic, were significantly more likely to use their machine and to return for a 1-month clinic visit than were those in the control group.\n Viewing of a patient education video at the initial visit was found to significantly improve the rate of return for the follow-up visit.", "Interventions to improve treatment outcomes in sleep apnoea-hypopnoea syndrome (SAHS) have had mixed success. Most have concentrated on following the use of a continuous positive airway pressure (CPAP) machines; poorer users may not return for machine readings, so any compliance study must take into account rates of attendance rates. We hypothesised that a series of additional, early support measures would improve re-attendance over a sustained period.\n Prospective, single-blinded interventional study. Seventy-two consecutive patients starting CPAP for SAHS were randomised to receive standard follow-up or extra early support. Attendance rates, CPAP use, Epworth scores, side-effects scores and number of changes to equipment were compared, by intent to treat, in both groups at 1 and 12 months.\n Re-attendance rates were higher in the intervention group at 1 month (P=0.04), 6 months (P=0.07) and 12 months (P=0.12). Those who defaulted tended previously to be poor users of the CPAP machine. For those who re-attended there was no difference in machine use or other outcomes.\n Simple interventions while commencing CPAP improve re-attendance with maximal benefit early on. This could provide more opportunities for solving problems early or considering alternative treatments. By confirming that poorer CPAP users eventually have higher default rates we recommend that future studies on CPAP compliance should first account for re-attendance rates." ]

[ "2283608", "11136307", "18476202", "8209936", "1907447", "8443666", "2143426" ]

[ "Electrosurgical skin incision versus conventional scalpel: a prospective trial.", "Randomized clinical trial of diathermy versus scalpel incision in elective midline laparotomy.", "Abdominal wound problems after hysterectomy with electrocautery vs. scalpel subcutaneous incision.", "Electrocautery used to create incisions does not increase wound infection rates.", "A prospective study of incisional time, blood loss, pain, and healing with carbon dioxide laser, scalpel, and electrosurgery.", "Comparative study of abdominal incision techniques.", "Wound infection after abdominal incision with scalpel or diathermy." ]

[ "A controlled clinical study comparing skin incision by conventional scalpel with electrosurgical needle incision has shown the latter technique to be highly effective, consistently quicker, and to give better cosmetic results with minimal complications. It is a convenient technique and well tolerated by the patients with no added discomfort. Skin diathermy burns and wound haematomas were only seen after conventional scalpel incision. Fears of delayed wound healing, keloid formation and high infection rates are unfounded.", "Electrocautery is used increasingly for tissue dissection, although fears of excessive scarring and poor wound healing have curtailed its widespread use for skin incision. This study compared electrosurgical incision with traditional scalpel incision.\n One hundred patients requiring elective midline laparotomy were randomized prospectively to either scalpel or diathermy incision. Parameters measured included incision time, wound size, wound blood loss, total intraoperative blood loss and postoperative wound pain. All wound complications were recorded.\n The two groups did not differ significantly in relation to patient or wound characteristics. Laparotomy incisions using diathermy were significantly quicker than scalpel incisions (mean(s. e.m.) 6.1(0.4) versus 7.5(0.5) s/cm2; P < 0.04). There was significantly less blood loss in the diathermy group compared with the scalpel group (0.8(0.1) versus 1.7(0.3) ml/cm2; P = 0.002). Postoperative pain scores were significantly lower in the diathermy group for the first 48 h after operation (P < 0.05). Morphine requirements were also significantly lower over the first 5 postoperative days in the diathermy incision group (P < 0.04). There was no difference between groups in wound complications before discharge and at the 1-month follow-up.\n Electrosurgical midline incision in elective surgery has significant advantages over scalpel use on the basis of incision time, blood loss, early postoperative pain and analgesia requirements.", "The purpose of this study was to evaluate the relationship between postoperative abdominal incision problems and opening subcutaneous tissues with electrocautery or scalpel. Women scheduled for elective abdominal hysterectomy who gave informed consent were randomly assigned to subcutaneous abdominal wall tissue incision by electrocautery or scalpel. Postoperative abdominal wound problem diagnoses included seroma, hematoma, infection, or dehiscence without identifiable etiology. Fifteen of 380 women (3.9%) developed a wound problem; six had scalpel and nine had electrosurgical subcutaneous incisions (P = 0.4). Thicker subcutaneous tissues (P = 0.04) and concurrent pelvic infection (P < 0.001) were significant risk factors for postoperative wound problems. Only two women (0.5%) developed an infection. We conclude that the method of subcutaneous tissue incision was unrelated to the development of postoperative abdominal incision problems in 380 women undergoing elective abdominal hysterectomy.", "A prospective, randomized, blinded clinical trial was conducted to determine whether electrocautery as a means of creating abdominal or thoracic wounds would result in increased wound infection rates. Over a 15-month period, 492 consecutively studied patients were randomly placed into 1 of 2 groups: scalpel or electrocautery. There were no differences in age grouping, use of steroids, incidence of diabetes, number of days preoperative, operative time, use of preoperative antibiotic prophylaxis, use of drains, number of obese patients, or gender ratio. Wound infections developed in 38 of the 250 scalpel patients (15%) and in 30 of the 242 cautery patients (12%). The use of electrocautery to create surgical wounds does not increase wound infection rates.", "Carbon dioxide laser incisions are reported to be less painful, less bloody, and less prone to seroma formation and to heal better than scalpel or electrosurgical incisions. We compared all three modalities in a prospective randomized study of cholecystectomy incisions. Time required for the incision and incisional blood loss was less with electrosurgery than with the carbon dioxide laser or scalpel. Postoperative pain and wound healing, however, were the same for all three techniques. The carbon dioxide laser appears to offer no advantage over conventional means of making a standard incision.", "The characteristics of surgical incisions made with an electrosurgical technique were compared with those made using conventional methods in a prospective randomized trial. In particular, the claim that the method of incision may influence postoperative pain was investigated. A total of 101 consecutive patients receiving full-length midline laparotomy incisions for gastrointestinal resection were studied. A record was kept of the time required to make the incision and blood loss as well as postoperative pain (using a linear analogue scale), ventilatory function and requirement for analgesia. There were 50 patients in group 1 (scalpel; 15 men, 35 women) and 51 in group 2 (electrocautery; 26 men, 25 women). The groups were similar in age, body-weight, diagnosis and the type of surgical procedures being performed. Incision time was similar in the two groups but median blood loss during incision was significantly less in group 2 patients than in group 1 (10 versus 25 ml, P < 0.0001). Linear analogue pain scores were not significantly different between the groups at any stage after operation. The same was true of postoperative ventilatory function and requirement for analgesia. A total value for morphine use during the entire postoperative period was derived for each group and the median was 1.55 mg/kg for group 1 compared with 1.49 mg/kg for group 2. The electrosurgical method is associated with less blood loss during incision, although this study has failed to confirm any reduction in postoperative pain or requirement for analgesia in these patients.", "nan" ]

[ "9175947", "16452355", "10356137" ]

[ "Randomised trial of dopamine compared with hydrocortisone for the treatment of hypotensive very low birthweight infants.", "A double-blind, randomized, controlled study of a \"stress dose\" of hydrocortisone for rescue treatment of refractory hypotension in preterm infants.", "Single-dose dexamethasone treatment of hypotension in preterm infants." ]

[ "To compare the efficacy of hydrocortisone with dopamine for the treatment of hypotensive, very low birthweight (VLBW) infants.\n Forty infants were randomly allocated to receive either hydrocortisone (n = 21) or dopamine (n = 19).\n All 19 infants randomised to dopamine responded; 17 of 21 (81%) did so in the hydrocortisone group. Three of the four non-responders in the hydrocortisone group had clinically significant left to right ductal shunting. The incidence of bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular haemorrhage, necrotising enterocolitis, symptomatic patent ductus arteriosus, hyperglycaemia, sepsis (bacterial or fungal) or survival did not differ between groups. The adrenocorticotrophic hormone (ACTH) stimulated plasma cortisol activity, either before or after treatment, did not differ between the two groups of infants. Although a significant difference in efficacy between dopamine and hydrocortisone was not noted (P = 0.108), there were four treatment failures in the hydrocortisone group, compared with none in the dopamine group.\n Both hydrocortisone and dopamine are effective treatments for hypotension in very low birthweight infants.", "To assess the effectiveness of a \"stress dose\" of hydrocortisone for rescue treatment of refractory hypotension and adrenocortical insufficiency of prematurity in very low birth weight (VLBW) infants. We hypothesized that significantly more VLBW infants who were receiving dopamine > or =10 microg/kg per min could wean off vasopressor support 72 hours after treatment with hydrocortisone.\n A double-blind, randomized, controlled study was conducted in a university neonatal center. Forty-eight VLBW infants who had refractory hypotension and required dopamine > or =10 microg/kg per min were randomly assigned to receive a stress dose of hydrocortisone (1 mg/kg every 8 hours for 5 days; n = 24) or an equivalent volume of the placebo solution (isotonic saline; n = 24).\n The baseline clinical characteristics were similar between the groups. Serum cortisol concentrations were very low immediately before randomization in both groups of infants. Significantly more VLBW infants who were treated with hydrocortisone weaned off vasopressor support 72 hours after starting treatment. The use of volume expander, cumulative dose of dopamine, and dobutamine were significantly less in hydrocortisone-treated infants compared with control infants. In addition, the median duration of vasopressor treatment was halved in hydrocortisone-treated patients. Two versus 11 infants in the hydrocortisone and control groups required a second vasopressor for treatment of refractory hypotension. The trend (linear and quadratic) of the mean arterial blood pressure was also significantly and consistently higher in hydrocortisone-treated infants.\n A stress dose of hydrocortisone was effective in treating refractory hypotension in VLBW infants. Although routine and prophylactic use of systemic corticosteroids could not be recommended because of their potential adverse effects, this relatively low dose of hydrocortisone would probably be preferable to high-dose dexamethasone for treatment of refractory hypotension in emergency and life-threatening situations.", "To test the efficacy of single-dose dexamethasone (DXM) in the management of severe arterial hypotension of newborn infants. Our hypothesis was that epinephrine infusions could be discontinued in 70% of patients within 12 hours after DXM administration compared with 10% in the placebo group.\n Twenty preterm infants (median birth weight 690 g, gestational age 28 weeks, age at intervention 2 days) who did not respond to a standardized treatment protocol (blood/colloid followed by dopamine infusion stepwise increased to 15 micrograms/kg and minute) were started on an epinephrine infusion and were randomly allocated to receive either DXM (0.25 mg/kg) or placebo intravenously. The primary outcome criterion was the need for an epinephrine infusion 12 hours after treatment.\n Three infants were excluded. Epinephrine infusion was discontinued in 5 of 8 infants with DXM but in only 1 of 9 infants in the control group. The duration of epinephrine infusion was significantly shorter in the DXM group (exact log-rank test, P =. 023).\n DXM was effective for the management of severe arterial hypotension in preterm infants not responding to standardized treatment." ]

[ "20164485", "20207412", "15901862", "21292711" ]

[ "Newborn-care training and perinatal mortality in developing countries.", "Effect of scaling up women's groups on birth outcomes in three rural districts in Bangladesh: a cluster-randomised controlled trial.", "An intervention involving traditional birth attendants and perinatal and maternal mortality in Pakistan.", "Effect of training traditional birth attendants on neonatal mortality (Lufwanyama Neonatal Survival Project): randomised controlled study." ]

[ "Of the 3.7 million neonatal deaths and 3.3 million stillbirths each year, 98% occur in developing countries. An evaluation of community-based interventions designed to reduce the number of these deaths is needed.\n With the use of a train-the-trainer model, local instructors trained birth attendants from rural communities in six countries (Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan, and Zambia) in the World Health Organization Essential Newborn Care course (which focuses on routine neonatal care, resuscitation, thermoregulation, breast-feeding, \"kangaroo\" [skin-to-skin] care, care of the small baby, and common illnesses) and (except in Argentina) in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (which teaches basic resuscitation in depth). The Essential Newborn Care intervention was assessed among 57,643 infants with the use of a before-and-after design. The Neonatal Resuscitation Program intervention was assessed as a cluster-randomized, controlled trial involving 62,366 infants. The primary outcome was neonatal death in the first 7 days after birth.\n The 7-day follow-up rate was 99.2%. After birth attendants were trained in the Essential Newborn Care course, there was no significant reduction from baseline in the rate of neonatal death from all causes in the 7 days after birth (relative risk with training, 0.99; 95% confidence interval [CI], 0.81 to 1.22) or in the rate of perinatal death; there was a significant reduction in the rate of stillbirth (relative risk with training, 0.69; 95% CI, 0.54 to 0.88; P=0.003). In clusters of births in which attendants had been randomly assigned to receive training in the Neonatal Resuscitation Program, as compared with control clusters, there was no reduction in the rates of neonatal death in the 7 days after birth, stillbirth, or perinatal death.\n The rate of neonatal death in the 7 days after birth did not decrease after the introduction of Essential Newborn Care training of community-based birth attendants, although the rate of stillbirths was reduced. Subsequent training in the Neonatal Resuscitation Program did not significantly reduce the mortality rates. (ClinicalTrials.gov number, NCT00136708.)\n 2010 Massachusetts Medical Society", "Two recent trials have shown that women's groups can reduce neonatal mortality in poor communities. We assessed the effectiveness of a scaled-up development programme with women's groups to address maternal and neonatal care in three rural districts of Bangladesh.\n 18 clusters (with a mean population of 27 953 [SD 5953]) in three districts were randomly assigned to either intervention or control (nine clusters each) by use of stratified randomisation. For each district, cluster names were written on pieces of paper, which were folded and placed in a bottle. The first three cluster names drawn from the bottle were allocated to the intervention group and the remaining three to control. All clusters received health services strengthening and basic training of traditional birth attendants. In intervention clusters, a facilitator convened 18 groups every month to support participatory action and learning for women, and to develop and implement strategies to address maternal and neonatal health problems. Women were eligible to participate if they were aged 15-49 years, residing in the project area, and had given birth during the study period (Feb 1, 2005, to Dec 31, 2007). Neither study investigators nor participants were masked to treatment assignment. In a population of 229 195 people (intervention clusters only), 162 women's groups provided coverage of one group per 1414 population. The primary outcome was neonatal mortality rate (NMR). Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN54792066.\n We monitored outcomes for 36 113 births (intervention clusters, n=17 514; control clusters, n=18 599) in a population of 503 163 over 3 years. From 2005 to 2007, there were 570 neonatal deaths in the intervention clusters and 656 in the control clusters. Cluster-level mean NMR (adjusted for stratification and clustering) was 33.9 deaths per 1000 livebirths in the intervention clusters compared with 36.5 per 1000 in the control clusters (risk ratio 0.93, 95% CI 0.80-1.09).\n For participatory women's groups to have a significant effect on neonatal mortality in rural Bangladesh, detailed attention to programme design and contextual factors, enhanced population coverage, and increased enrolment of newly pregnant women might be needed.\n Women and Children First, the UK Big Lottery Fund, Saving Newborn Lives, and the UK Department for International Development.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "There are approximately 4 million neonatal deaths and half a million maternal deaths worldwide each year. There is limited evidence from clinical trials to guide the development of effective maternity services in developing countries.\n We performed a cluster-randomized, controlled trial involving seven subdistricts (talukas) of a rural district in Pakistan. In three talukas randomly assigned to the intervention group, traditional birth attendants were trained and issued disposable delivery kits; Lady Health Workers linked traditional birth attendants with established services and documented processes and outcomes; and obstetrical teams provided outreach clinics for antenatal care. Women in the four control talukas received usual care. The primary outcome measures were perinatal and maternal mortality.\n Of the estimated number of eligible women in the seven talukas, 10,114 (84.3 percent) were recruited in the three intervention talukas, and 9443 (78.7 percent) in the four control talukas. In the intervention group, 9184 women (90.8 percent) received antenatal care by trained traditional birth attendants, 1634 women (16.2 percent) were seen antenatally at least once by the obstetrical teams, and 8172 safe-delivery kits were used. As compared with the control talukas, the intervention talukas had a cluster-adjusted odds ratio for perinatal death of 0.70 (95 percent confidence interval, 0.59 to 0.82) and for maternal mortality of 0.74 (95 percent confidence interval, 0.45 to 1.23).\n Training traditional birth attendants and integrating them into an improved health care system were achievable and effective in reducing perinatal mortality. This model could result in large improvements in perinatal and maternal health in developing countries.\n Copyright 2005 Massachusetts Medical Society.", "To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a resource poor country with limited access to healthcare.\n Prospective, cluster randomised and controlled effectiveness study.\n Lufwanyama, an agrarian, poorly developed district located in the Copperbelt province, Zambia. All births carried out by study birth attendants occurred at mothers' homes, in rural village settings.\n 127 traditional birth attendants and mothers and their newborns (3559 infants delivered regardless of vital status) from Lufwanyama district.\n Using an unblinded design, birth attendants were cluster randomised to intervention or control groups. The intervention had two components: training in a modified version of the neonatal resuscitation protocol, and single dose amoxicillin coupled with facilitated referral of infants to a health centre. Control birth attendants continued their existing standard of care (basic obstetric skills and use of clean delivery kits).\n The primary outcome was the proportion of liveborn infants who died by day 28 after birth, with rate ratios statistically adjusted for clustering. Secondary outcomes were mortality at different time points; and comparison of causes of death based on verbal autopsy data.\n Among 3497 deliveries with reliable information, mortality at day 28 after birth was 45% lower among liveborn infants delivered by intervention birth attendants than control birth attendants (rate ratio 0.55, 95% confidence interval 0.33 to 0.90). The greatest reductions in mortality were in the first 24 hours after birth: 7.8 deaths per 1000 live births for infants delivered by intervention birth attendants compared with 19.9 per 1000 for infants delivered by control birth attendants (0.40, 0.19 to 0.83). Deaths due to birth asphyxia were reduced by 63% among infants delivered by intervention birth attendants (0.37, 0.17 to 0.81) and by 81% within the first two days after birth (0.19, 0.07 to 0.52). Stillbirths and deaths from serious infection occurred at similar rates in both groups.\n Training traditional birth attendants to manage common perinatal conditions significantly reduced neonatal mortality in a rural African setting. This approach has high potential to be applied to similar settings with dispersed rural populations. Trial registration Clinicaltrials.gov NCT00518856." ]

[ "12181083", "8701750" ]

[ "[Clinical efficacy and safety of huperzine Alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial].", "Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease." ]

[ "To evaluate the clinical efficacy and safety of huperzine Alpha in treatment of patients with mild to moderate Alzheimer disease (AD).\n Two hundred and two patients with the diagnosis of possible or probable AD from 15 centers the nationwide were randomly divided into two groups: huperzine Alpha group (n = 100, given huperzine Alpha 400 micro g/day for 12 weeks) and placebo group (n = 102 ). Different scales were used to evaluate the cognitive function, activity of daily life (ADL), non-cognitive disorders, and overall clinical efficacy. Safety evaluation was conducted every 6 weeks.\n In comparison with the baseline data, there was an improvement of 4.6 points in cognition assessed by ADAS-Cog (P = 0.000); an improvement of 2.7 points by MMSE (P = 0.000), an improvement of 1.5 points in behavior and mood by ADAS-non-Cog (P = 0.008) with 59.2% of the patients being on the mend clinically; and an improvement of 2.4 points by ADL (P = 0.001) with the capacity of ADL improved by at least 10% among 32.75% of the patients. 70% of the patients in huperzine Alpha group scored 1 approximately 3 points, and 27.8% of them scored 1 approximately 2 points by CIBIC-plus. The proportions of patients with an improvement of >/= 4 points by ADAS-Cog were 56.1% and 12.5% in the huperzine Alpha group and placebo group respectively (P = 0.000). The proportions of patients with an improvement of >/= 4 points by MMSE were 37.8% and 10.1% in the huperzine Alpha group and placebo group respectively (P = 0.000). The proportions of patients with an improvement of 1 approximately 3 points in global rating by CIBIC-plus were 59.2% and 40.6% in the huperzine Alpha group and placebo group respectively (P = 0.01). The proportions of patients with an improvement of >/= 10% points by ADL were 32.7% and 17.2% in the huperzine Alpha group and placebo group respectively (P = 0.01). The proportions of patients with an improvement of > 0 points by ADS-non-C0g were 70.0% and 36.3% in the huperzine Alpha group and placebo group respectively (P = 0.000). Mild and transient adverse events (edema of bilateral ankles and insomnia) were observed in 3% of huperzine Alpha treated patients.\n A safe and effective medicine, huperzine Alpha remarkably improves the cognition, behavior, ADL,and mood of AD patients.", "To evaluate the efficacy and safety of tablet huperzine-A (Hup) in patients with Alzheimer's disease.\n Using multicenter, prospective, double-blind, parallel, placebo controlled and randomized method, 50 patients were administered orally 0.2 mg (4 tablets) Hup and 53 patients were given po 4 tablets of placebo bid for 8 wk. All patients were evaluated with Wechsler memory scale, Hasegawa dementia scale, mini-mental state examination scale, activity of daily living scale, treatment emergency symptom scale, and measured with BP, HR, ECG, EEG, ALT, AKP, BUN, Cr, Hb, WBC, and urine routine.\n About 58% (29/50) of patients treated with Hup showed improvements in their memory (P < 0.01), cognitive (P < 0.01), and behavioral (P < 0.01 functions. The efficacy of Hup was better than placebo (36%, 19/53) (P < 0.05). No severe side effect was found.\n Hup is a promising drug for symptomatic treatment of Alzheimer's disease." ]

[ "20422000", "18955452", "17101295", "15624138", "10968436", "17473138", "17550302", "17599746", "17326054", "17493109", "15589488", "15928613", "12213183", "16199844", "3772583", "8285810", "16879680", "17641106", "20738476", "16495012", "11463678", "12893670", "18760766", "16893480", "20624806", "8602706", "17609679", "20679560", "16449469", "16889157", "19213766", "20015404", "19880289", "14970094", "12928469", "12153921", "16705108", "19503811", "11116769", "17954797", "19000234", "18583463", "17602130", "10834855", "19887933", "14982982", "15588746" ]

[ "Relationship between sponsorship and failure rate of dental implants: a systematic approach.", "Evolution of the randomized controlled trial in oncology over three decades.", "Association of industry sponsorship to published outcomes in gastrointestinal clinical research.", "Epidemiologic studies of adverse effects of anti-retroviral drugs: how well is statistical power reported.", "The uncertainty principle and industry-sponsored research.", "Commercially funded and United States-based research is more likely to be published; good-quality studies with negative outcomes are not.", "Factors associated with findings of published trials of drug-drug comparisons: why some statins appear more efficacious than others.", "Glucosamine for pain in osteoarthritis: why do trial results differ?", "Association between pharmaceutical involvement and outcomes in breast cancer clinical trials.", "The impact of pharmaceutical company funding on results of randomized trials of nicotine replacement therapy for smoking cessation: a meta-analysis.", "Association of funding and findings of pharmaceutical research at a meeting of a medical professional society.", "Extent and impact of industry sponsorship conflicts of interest in dermatology research.", "Funding source, trial outcome and reporting quality: are they related? Results of a pilot study.", "Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry.", "Source of funding and outcome of clinical trials.", "A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of arthritis.", "A meta-analysis comparing trials of antimuscarinic medications funded by industry or not.", "The relationship between the outcome of studies of autologous chondrocyte implantation and the presence of commercial funding.", "A comparison of the scientific quality of publicly and privately funded randomized controlled drug trials.", "Bias from industry trial funding? A framework, a suggested approach, and a negative result.", "Third generation oral contraceptives and risk of venous thrombosis: meta-analysis.", "Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination.", "Discrepancy between results and abstract conclusions in industry- vs nonindustry-funded studies comparing topical prostaglandins.", "Relationship between drug company funding and outcomes of clinical psychiatric research.", "Assessment of risk of bias among pediatric randomized controlled trials.", "The quality of drug studies published in symposium proceedings.", "Issues that may determine the outcome of antipsychotic trials: industry sponsorship and extrapyramidal side effect.", "Outcome reporting among drug trials registered in ClinicalTrials.gov.", "Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics.", "Publication bias in the pulmonary/allergy literature: effect of pharmaceutical company sponsorship.", "Relation of study quality, concordance, take home message, funding, and impact in studies of influenza vaccines: systematic review.", "Association of trial registration with the results and conclusions of published trials of new oncology drugs.", "The effect of study sponsorship on a systematically evaluated body of evidence of head-to-head trials was modest: secondary analysis of a systematic review.", "Association between industry funding and statistically significant pro-industry findings in medical and surgical randomized trials.", "Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events?", "Association between competing interests and authors' conclusions: epidemiological study of randomised clinical trials published in the BMJ.", "Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-for-profit organizations: 2000-2005.", "Factors associated with results and conclusions of trials of thiazolidinediones.", "Predictive value of pharmacological activity for the relative efficacy of antidepressant drugs. Meta-regression analysis.", "Adverse effects of inhaled corticosteroids in funded and nonfunded studies.", "The quality of reporting of randomized controlled trials in solid organ transplantation.", "Quality of reporting of randomized controlled trials in general endocrinology literature.", "Influence of drug company authorship and sponsorship on drug trial outcomes.", "Epidemiology of research into interventions for the treatment of osteoarthritis of the knee joint.", "Association between research sponsorship and study outcome in plastic surgery literature.", "Industry sponsorship and authorship of clinical trials over 20 years.", "An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia." ]

[ "The number of dental implant treatments increases annually. Dental implants are manufactured by competing companies. Systematic reviews and meta-analysis have shown a clear association between pharmaceutical industry funding of clinical trials and pro-industry results. So far, the impact of industry sponsorship on the outcomes and conclusions of dental implant clinical trials has never been explored. The aim of the present study was to examine financial sponsorship of dental implant trials, and to evaluate whether research funding sources may affect the annual failure rate.\n A systematic approach was used to identify systematic reviews published between January 1993 and December 2008 that specifically deal with the length of survival of dental implants. Primary articles were extracted from these reviews. The failure rate of the dental implants included in the trials was calculated. Data on publication year, Impact Factor, prosthetic design, periodontal status reporting, number of dental implants included in the trials, methodological quality of the studies, presence of a statistical advisor, and financial sponsorship were extracted by two independent reviewers (kappa = 0.90; CI(95%) [0.77-1.00]). Univariate quasi-Poisson regression models and multivariate analysis were used to identify variables that were significantly associated with failure rates. Five systematic reviews were identified from which 41 analyzable trials were extracted. The mean annual failure rate estimate was 1.09%.(CI(95%) [0.84-1.42]). The funding source was not reported in 63% of the trials (26/41). Sixty-six percent of the trials were considered as having a risk of bias (27/41). Given study age, both industry associated (OR = 0.21; CI(95%) [0.12-0.38]) and unknown funding source trials (OR = 0.33; (CI(95%) [0.21-0.51]) had a lower annual failure rates compared with non-industry associated trials. A conflict of interest statement was disclosed in 2 trials.\n When controlling for other factors, the probability of annual failure for industry associated trials is significantly lower compared with non-industry associated trials. This bias may have significant implications on tooth extraction decision making, research on tooth preservation, and governmental health care policies.", "The randomized controlled trial (RCT) is the gold standard for establishing new therapies in clinical oncology. Here we document changes with time in design, sponsorship, and outcomes of oncology RCTs.\n Reports of RCTs evaluating systemic therapy for breast, colorectal (CRC), and non-small-cell lung cancer (NSCLC) published 1975 to 2004 in six major journals were reviewed. Two authors abstracted data regarding trial design, results, and conclusions. Conclusions of authors were graded using a 7-point Likert scale. For each study the effect size for the primary end point was converted to a summary measure.\n A total of 321 eligible RCTs were included (48% breast, 24% CRC, 28% NSCLC). Over time, the number and size of RCTs increased considerably. For-profit/mixed sponsorship increased substantially during the study period (4% to 57%; P < .001). There was increasing use of time-to-event measures (39% to 78%) and decreasing use of response rate (54% to 14%) as primary end point (P < .001). Effect size remained stable over the study period. Authors have become more likely to strongly endorse the experimental arm (P = .017). A significant P value for the primary end point and industry sponsorship were each independently associated with endorsement of the experimental agent (odds ratio [OR] = 19.6, 95% CI, 8.9 to 43.1, and OR = 3.5, 95% CI, 1.6 to 7.5, respectively).\n RCTs in oncology have become larger and are more likely to be sponsored by industry. Authors of modern RCTs are more likely to strongly endorse novel therapies. For-profit sponsorship and statistically significant results are independently associated with endorsement of the experimental arm.", "Recent years have seen an increase in industry sponsorship of clinical trials throughout medicine. We conducted a study to evaluate the association of industry sponsorship to published outcomes in gastrointestinal (GI) clinical research. Our aims were (1) to evaluate the trends in the source of funding for GI clinical research during the period from 1992 to 2002-2003, (2) to determine whether the source of study funding predicted the likelihood that a study would publish results that favor the drug or device being tested, and (3) to determine whether differences exist in the methodologic quality of the investigational study methods used in studies funded by private industry versus other sources.\n We selected all clinical studies evaluating a drug or device from 4 prominent GI journals (Gastroenterology, The American Journal of Gastroenterology, Hepatology, and Gastrointestinal Endoscopy). All studies were abstracted by using a standardized data abstraction form. We evaluated the trends in funding source for studies published during the years 1992, 2002, and 2003. All selected studies were scored for methodologic quality by using a previously validated scoring system. The percentage of studies that reported outcomes that favored the device or drug being tested against the standard therapy or placebo was determined for each funding source. A funnel plot was constructed to assess for the presence of negative publication bias.\n A total of 6326 studies were reviewed. For the 1992 trend data, 1860 studies were reviewed, and 135 were selected for inclusion in the study. Ninety-five studies were studies involving the investigation of drugs, and 40 studies involved the testing of a device. For the 2002-2003 data 4466 studies were reviewed, and 315 were selected for inclusion in the study. Two hundred twenty-two studies were clinical trials involving the investigation of drugs, and 93 were clinical trials involving devices. In comparing 1992 to 2002, the percentage of studies funded by industry sources more than doubled from 10% to greater than 28% of the total studies assessed. There was an associated decline in the proportion of studies with funding from non-industry sources during this period (62% to less than 48%). The percentage of studies that did not disclose a funding source fell modestly from 28% to 24%. We found that 86% of studies funded by private industry reported a result favorable to the study drug or device, and 83% of studies funded by academic sources reported a result favorable to the study drug or device (P=.572). On average, studies funded by private industry had a higher methodology score than studies funded by traditional academic sources (75 of 100 vs 65 of 100; P=.005). Analysis of the funnel plot did not reveal evidence of bias against the publication of small studies with insignificant results.\n The proportion of research funded by industry has more than doubled during the last decade and currently comprises almost half of the funding for GI clinical research. Industry-sponsored studies are, on average, of superior methodologic quality to studies funded by other sources. Industry-sponsored studies in leading GI journals were no more likely than other studies to publish results that favored the study sponsor, although an extremely high percentage of all studies in these journals reported positive results. There has been only a modest decline in studies not acknowledging a funding source.", "To determine whether there is a difference in average statistical power between pharmacoepidemiologic studies of anti-retroviral adverse drug effects (ADEs) sponsored by for-profit versus non-profit organizations.\n We studied all published pharmacoepidemiologic studies of ADEs associated with the 15 anti-retroviral drugs approved through the end of 1999. A priori, the primary outcome was the power of each study to detect a clinically important difference in the risk for an adverse effect among patients exposed to the study drug(s). We could not evaluate this outcome because of the infrequent reporting of power calculations. We instead report the distribution of studies across a 5-tiered measure of adequacy of reporting of statistical power, as well as the sponsorship of these studies.\n Of 48 studies meeting our inclusion criteria, only 1 (2%) reported either a completed, a priori power calculation or sufficient details for readers to calculate the power to detect a pre-defined, clinically important effect. Thirty-five studies (73%) reported the minimum information required for sophisticated readers to determine the power to detect an event rate of interest to them; 6 additional studies (13%) reported confidence intervals around at least one summary effect measure and 6 (13%) provided no indication of power or uncertainty. Of the 41 studies for which sponsorship was determined, only 3 (7%) were sponsored by for-profit organizations.\n The poor reporting of statistical power in this sample suggests a need for guidelines to improve the reporting of pharmacoepidemiologic studies of ADEs. Future research is needed to determine whether the observed paucity of industry-sponsored observational studies of anti-retroviral ADEs extends to other clinical areas, and if so, to identify the causes of this phenomenon.\n Copyright 2004 John Wiley & Sons, Ltd.", "Reporting of pharmaceutical-industry-sponsored randomised clinical trials often result in biased findings, either due to selective reporting of studies with non-equivalent arms or publication of low-quality papers, wherein unfavourable results are incompletely described. A randomised trial should be conducted only if there is substantial uncertainty about the relative value of one treatment versus another. Studies in which intervention and control are thought to be non-equivalent violates the uncertainty principle.\n We examined the quality of 136 published randomised trials that focused on one disease category (multiple myeloma) and adherence to the uncertainty principle. To evaluate whether the uncertainty principle was upheld, we compared the number of studies favouring experimental treatments over standard ones. We analysed data according to the source of funding.\n Trials funded solely or in part by 35 profit-making organisations had a trend toward higher quality scores (mean 2.94 [SD 1.3]; median 3) than randomised trials supported by 95 governmental or other non-profit organisations (2.4 [0.8]; 2; p=0.06). Overall, the uncertainty principle was upheld, with 44% of randomised trials favouring standard treatments and 56% innovative treatments (p=0.17); mean and median preference evaluation scores were 3.7 (1.0) and 4. However, when the analysis was done according to the source of funding, studies funded by non-profit organisations maintained equipoise favouring new therapies over standard ones (47% vs 53%; p=0.608) to a greater extent than randomised trials supported solely or in part by profit-making organisations (74% vs 26%; p=0.004).\n The reported bias in research sponsored by the pharmaceutical industry may be a consequence of violations of the uncertainty principle. Sponsors of clinical trials should be encouraged to report all results and to choose appropriate comparative controls.", "Prior studies implying associations between receipt of commercial funding and positive (significant and/or pro-industry) research outcomes have analyzed only published papers, which is an insufficiently robust approach for assessing publication bias. In this study, we tested the following hypotheses regarding orthopaedic manuscripts submitted for review: (1) nonscientific variables, including receipt of commercial funding, affect the likelihood that a peer-reviewed submission will conclude with a report of a positive study outcome, and (2) positive outcomes and other, nonscientific variables are associated with acceptance for publication.\n All manuscripts about hip or knee arthroplasty that were submitted to The Journal of Bone and Joint Surgery, American Volume, over seventeen months were evaluated to determine the study design, quality, and outcome. Analyses were carried out to identify associations between scientific factors (sample size, study quality, and level of evidence) and study outcome as well as between non-scientific factors (funding source and country of origin) and study outcome. Analyses were also performed to determine whether outcome, scientific factors, or nonscientific variables were associated with acceptance for publication.\n Two hundred and nine manuscripts were reviewed. Commercial funding was not found to be associated with a positive study outcome (p = 0.668). Studies with a positive outcome were no more likely to be published than were those with a negative outcome (p = 0.410). Studies with a negative outcome were of higher quality (p = 0.003) and included larger sample sizes (p = 0.05). Commercially funded (p = 0.027) and United States-based (p = 0.020) studies were more likely to be published, even though those studies were not associated with higher quality, larger sample sizes, or lower levels of evidence (p = 0.24 to 0.79).\n Commercially funded studies submitted for review were not more likely to conclude with a positive outcome than were nonfunded studies, and studies with a positive outcome were no more likely to be published than were studies with a negative outcome. These findings contradict those of most previous analyses of published (rather than submitted) research. Commercial funding and the country of origin predict publication following peer review beyond what would be expected on the basis of study quality. Studies with a negative outcome, although seemingly superior in quality, fared no better than studies with a positive outcome in the peer-review process; this may result in inflation of apparent treatment effects when the published literature is subjected to meta-analysis.", "Published pharmaceutical industry-sponsored trials are more likely than non-industry-sponsored trials to report results and conclusions that favor drug over placebo. Little is known about potential biases in drug-drug comparisons. This study examined associations between research funding source, study design characteristics aimed at reducing bias, and other factors that potentially influence results and conclusions in randomized controlled trials (RCTs) of statin-drug comparisons.\n This is a cross-sectional study of 192 published RCTs comparing a statin drug to another statin drug or non-statin drug. Data on concealment of allocation, selection bias, blinding, sample size, disclosed funding source, financial ties of authors, results for primary outcomes, and author conclusions were extracted by two coders (weighted kappa 0.80 to 0.97). Univariate and multivariate logistic regression identified associations between independent variables and favorable results and conclusions. Of the RCTs, 50% (95/192) were funded by industry, and 37% (70/192) did not disclose any funding source. Looking at the totality of available evidence, we found that almost all studies (98%, 189/192) used only surrogate outcome measures. Moreover, study design weaknesses common to published statin-drug comparisons included inadequate blinding, lack of concealment of allocation, poor follow-up, and lack of intention-to-treat analyses. In multivariate analysis of the full sample, trials with adequate blinding were less likely to report results favoring the test drug, and sample size was associated with favorable conclusions when controlling for other factors. In multivariate analysis of industry-funded RCTs, funding from the test drug company was associated with results (odds ratio = 20.16 [95% confidence interval 4.37-92.98], p < 0.001) and conclusions (odds ratio = 34.55 [95% confidence interval 7.09-168.4], p < 0.001) that favor the test drug when controlling for other factors. Studies with adequate blinding were less likely to report statistically significant results favoring the test drug.\n RCTs of head-to-head comparisons of statins with other drugs are more likely to report results and conclusions favoring the sponsor's product compared to the comparator drug. This bias in drug-drug comparison trials should be considered when making decisions regarding drug choice.", "Investigators in trials of glucosamine report a range of estimates for efficacy, making conclusions difficult. We undertook this study to identify factors that explain heterogeneity in trials of glucosamine.\n We searched for reports of trial results in Ovid Medline, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and proceedings of scientific conferences. We selected reports of randomized, double-blind, placebo-controlled trials of glucosamine for pain from osteoarthritis of the knee or hip. We extracted data regarding features of design, subjects, and markers of industry involvement, including industry funding, whether a drug was supplied by industry, industry participation, and industry-affiliated authorship. We examined which factors best accounted for differences in the effect sizes of studies grouped by these characteristics, and we examined changes in I(2), a measure of heterogeneity.\n Fifteen trials met our inclusion criteria. The summary effect size was 0.35 (95% confidence interval 0.14, 0.56). I(2) was 0.80. Except for allocation concealment, no feature of study design explained this substantial heterogeneity. Summary effect sizes ranged from 0.05 to 0.16 in trials without industry involvement, but the range was 0.47-0.55 in trials with industry involvement. The effect size was 0.06 for trials using glucosamine hydrochloride and 0.44 for trials using glucosamine sulfate. Trials using Rottapharm products had an effect size of 0.55, compared with 0.11 for the rest.\n Heterogeneity among trials of glucosamine is larger than would be expected by chance. Glucosamine hydrochloride is not effective. Among trials with industry involvement, effect sizes were consistently higher. Potential explanations include different glucosamine preparations, inadequate allocation concealment, and industry bias.", "Since 1992, pharmaceutical industry support has surpassed National Institutes of Health funding for clinical research in the United States. In this study, the authors sought to evaluate the impact of this shift in funding from public to private sponsors on the nature of published breast cancer clinical research.\n All published breast cancer clinical trials from 2003, 1998, and 1993 were reviewed from 10 select English-language medical journals to evaluate pharmaceutical involvement over time and the association between sponsorship, trial design, and results. Clinical studies that reported disease-specific outcomes from medical therapy for breast cancer were eligible for analysis. Pharmaceutical involvement was defined as reported pharmaceutical industry funding, provision of drug, and/or authorship for each publication.\n In total, 140 eligible studies were identified, including 45 studies that were published in 1993, 39 studies that were published in 1998, and 56 studies that were published in 2003. Among those, 67 publications (48%) reported pharmaceutical industry involvement, 36 publications (26%) had at least >/=1 pharmaceutical industry author, And 100 publications (71%) were considered positive. Pharmaceutical involvement was identified in 44% of the studies published in 1993, in 38% of the studies published in 1998, and in 58% of the studies published in 2003. Pharmaceutical authorship was reported in 22% of the 1993 studies, in 21% of the 1998 studies, and in 34% of the 2003 studies. For studies that were published in 2003, those that reported pharmaceutical involvement were more likely to be positive (84% vs 54%; P = .02; Fisher exact test), to be single-arm studies (66% vs 33%; P = .03), and to evaluate metastatic disease (72% vs 46%; P = .06).\n Pharmaceutical involvement in published clinical breast cancer research may affect study design, focus, and results. Further research is warranted, including analysis of unpublished studies, to evaluate the impact of increasing pharmaceutical industry involvement on clinical research.\n (c) 2007 American Cancer Society.", "To assess whether source of funding affected the results of trials of nicotine replacement therapy (NRT) for smoking cessation.\n We reviewed all randomized controlled trials included in the Cochrane review. There were insufficient non-industry trials of the newer products for these to be included. We included 90 trials of either the nicotine gum (52) or nicotine patch (38). They comprised 18 238 treatment and 16 235 control participants. Forty-nine showed evidence of industry support (18 gum, 31 patch).\n Industry (31 of 49, 63%) compared with non-industry (seven of 41, 17%, P < 0.001) supported a higher proportion of nicotine patch studies and had larger sample sizes (479 versus 268, P = 0.04). Twenty-five (51%) industry trials reported statistically significant (P < 0.05) results, compared with nine (22%) non-industry trials (OR = 3.70, 95% CI = 1.46-9.35). This difference was not explained by trial characteristics. Industry-supported trials had a pooled odds ratio of 1.90 (1.67-2.16), compared with 1.61 (1.43-1.80) for other studies (chi(2) = 3.6, P = 0.058). There was evidence of funnel-plot asymmetry among industry trials (t = 4.35, P < 0.001), but not among other trials, indicating that several small null-effect industry trials may not have reached publication. After imputation adjustment, the odds ratio for industry trials reduced to 1.64 (1.43-1.89) and the overall NRT odds ratio reduced from 1.73 (1.60-1.90) to 1.62 (1.49-1.77).\n Compared with independent trials, industry-supported trials were more likely to produce statistically significant results and larger odds ratios. These differences persisted after adjustment for basic trial characteristics. Although we had no data on the amount of funding for each trial, it is possible that more resources led to higher treatment compliance and therefore greater efficacy in industry-supported trials. Differences can also possibly be explained by publication bias with several small, null-effect industry studies not having reached publication. After adjustment for this possible bias, results for industry trials were lower and similar to non-industry results. Similarly, the overall estimate of the net effect for these products reduces to about 5% attributable 1-year successes. This remains of considerable public health benefit. Registration of clinical trials has become mandatory in many countries since most of the trials considered here were conducted, and this should reduce the potential for publication bias in future.", "To evaluate the association between funding and findings of pharmaceutical research presented at an annual meeting of a medical professional society.\n We reviewed the abstracts of all papers and posters presented at the annual meeting of a medical professional society. Two independent raters classified each study of a drug (n = 48) as either positive (favoring the drug studied) or negative, and as either funded by a pharmaceutical company or not. We computed kappa and chi-squared statistics to evaluate the agreement between the raters, as well as the association between the results and the sponsorship of the study.\n Thirty studies of drugs (63%) were supported by pharmaceutical companies, all of which reported positive results. Of the 18 studies (37%) not supported by pharmaceutical companies, 67% reported positive results. The association between pharmaceutical funding and positive findings was statistically significant (P = 0.0007).\n At this scientific meeting, research funding from pharmaceutical companies was associated with study findings that supported the use of drugs marketed by pharmaceutical sponsors. We emphasize further study of this relation and suggest three principles--full disclosure, policies against \"outcome bias,\" and educational opportunities--that may help manage industry-academia conflicts of interest that could otherwise jeopardize the credibility of pharmaceutical research presented at scientific meetings.", "Many published clinical trials are authored by investigators with financial conflicts of interest. The general medical literature documents the pervasive extent and sometimes problematic impact of these conflicts. Accordingly, there is renewed discussion about author disclosure and clinical trial registry to minimize publication bias from financial conflicts of interest. Despite this evolving discussion in the general medical literature, little is known about the extent or role of financial conflicts of interest in dermatology research.\n Our purpose was to determine the extent and impact of industry sponsorship conflicts of interest in dermatology research.\n We recorded potential financial conflicts of interest, study design, and study outcome in 179 clinical trials published between Oct 1, 2000 and Oct 1, 2003 in four leading dermatology journals.\n Forty-three percent of analyzed studies included at least one author with a reported conflict of interest. These studies were more likely to report a positive result, demonstrate higher methodological quality, and include a larger sample size.\n Conflict of interest in clinical investigations in dermatology appears to be prevalent and associated with potentially significant differences in study methodology and reporting.", "There has been increasing concern regarding the potential effects of the commercialization of research.\n In order to examine the relationships between funding source, trial outcome and reporting quality, recent issues of five peer-reviewed, high impact factor, general medical journals were hand-searched to identify a sample of 100 randomized controlled trials (20 trials/journal). Relevant data, including funding source (industry/not-for-profit/mixed/not reported) and statistical significance of primary outcome (favouring new treatment/favouring conventional treatment/neutral/unclear), were abstracted. Quality scores were assigned using the Jadad scale and the adequacy of allocation concealment.\n Sixty-six percent of trials received some industry funding. Trial outcome was not associated with funding source (p=.461). There was a preponderance of favourable statistical conclusions among published trials with 67% reporting results that favored a new treatment whereas 6% favoured the conventional treatment. Quality scores were not associated with funding source or trial outcome.\n It is not known whether the absence of significant associations between funding source, trial outcome and reporting quality reflects a true absence of an association or is an artefact of inadequate statistical power, reliance on voluntary disclosure of funding information, a focus on trials recently published in the top medical journals, or some combination thereof. Continued and expanded monitoring of potential conflicts is recommended, particularly in light of new guidelines for disclosure that have been endorsed by the ICMJE.", "Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied. The extent and implications of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated, to the authors' knowledge.\n The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry, the Archives of General Psychiatry, the Journal of Clinical Psychopharmacology, and the Journal of Clinical Psychiatry between 2001 and 2003.\n Among 397 clinical trials identified, 239 (60%) reported receiving funding from a pharmaceutical company or other interested party, and 187 studies (47%) included at least one author with a reported financial conflict of interest. Among the 162 randomized, double-blind, placebo-controlled studies examined, those that reported conflict of interest were 4.9 times more likely to report positive results; this association was significant only among the subset of pharmaceutical industry-funded studies.\n Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo.", "Because of recent concerns about conflicts of interest and published research, the author analyzed 107 controlled clinical trials. Studies were classified as favoring either a new therapy or a traditional therapy, and as being supported by a pharmaceutical manufacturer or as being generally supported. Seventy-one per cent of the trials favored new therapies; 43% of these were funded by pharmaceutical firms. Of the 31 trials favoring traditional therapy, only four (13%) were supported by a pharmaceutical firm. There was a statistically significant association between the source of funding and the outcome of the study (p = 0.002). Few trials supported by pharmaceutical manufacturers favored traditional therapy; some reasons for this finding may include selection of drugs likely to be proven efficacious, Type II errors (false-negative studies), and fear of discontinuation of funding should such studies be submitted. Important clinical information may be lost if negative studies are not published.", "To study the relation between reported drug performance in published trials and support of the trials by the manufacturer of the drug under evaluation, we studied a sample of trials of nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment of arthritis.\n All randomized control trials of NSAIDs published between September 1987 and May 1990 identified by MEDLINE were reviewed. If an article met the following criteria (n = 61), it was selected: trials involving adult patients with osteoarthritis or rheumatoid arthritis (n = 180), use of nonsalicylate NSAIDs marketed in the United States (n = 101), randomized control trial (n = 81), duration of the trial 4 or more days (n = 78), and use of an efficacy outcome measure (n = 61). Reviewers, \"blinded\" to manufacturer status, evaluated the narrative interpretation of results and extracted numeric data on efficacy and toxicity. Manufacturer-associated trials were defined as those that acknowledged an association with a pharmaceutical manufacturer. Because of the scarcity of non-manufacturer-associated trials (n = 9), we report only on the manufacturer-associated articles.\n Fifty-two publications (85.2%) representing 56 trials were associated with a manufacturer. The manufacturer-associated drug was reported as comparable with (71.4%) or superior to (28.6%) the comparison drug in all 56 trials. These narrative claims of superiority were usually justified with trial data. Of the trials identifying one drug as less toxic (n = 22), the manufacturer-associated drug's safety was reported as superior to the comparison drug in 86.4% of cases. Justification for the narrative interpretation of the trial findings regarding less toxicity was provided in only 12 (54.5%) of 22 trials.\n The manufacturer-associated NSAID is almost always reported as being equal or superior in efficacy and toxicity to the comparison drug. These claims of superiority, especially in regard to side effect profiles, are often not supported by trial data. These data raise concerns about selective publication or biased interpretation of results in manufacturer-associated trials.", "To determine if there is a significant difference in outcomes of clinical trials funded by industry or not of antimuscarinic medications used to treat overactive bladder (OAB) symptoms and detrusor overactivity (DOA).\n A Medline search was conducted from January 1966 to June 2003 to identify human clinical trials of oxybutynin and tolterodine published in English. Randomized controlled trials on subjects aged > or = 16 years who were being treated with oxybutynin or tolterodine for OAB symptoms or DOA; 24 studies were identified. The endpoints assessed were OAB symptoms or changes in uninhibited detrusor contractions on cystometrography. The outcome variables were dichotomized as 'improvement' or 'no improvement'. Odds ratios and 95% confidence intervals were calculated for each study based on data derived or extracted from tables and figures.\n Meta-analysis showed no significant difference in the outcomes trails funded by industry or not. Trials were then reviewed to determine their adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines for randomized trials.\n Clinical trials are important for clinicians when selecting medical therapies. In this analysis we found no difference in outcomes when comparing studies funded by industry or not for tolterodine and oxybutynin. The quality of all trials would be improved by close adherence to the CONSORT guidelines for randomized clinical trials.", "Autologous chondrocyte implantation (ACI) is an expensive treatment option for focal cartilage defects, and commercial funding of research is associated with a study reaching a positive conclusion. The purpose of this analysis is to compare outcomes (and levels of evidence) between published ACI outcome studies that were commercially funded and studies that were not commercially funded.\n Commercially funded ACI literature could be commercially biased.\n Comparative meta-analysis.\n MEDLINE was searched for human, knee, ACI, nonmembrane, English language, and clinical outcome studies. Studies were evaluated with regard to funding status (commercially funded or not commercially funded), outcomes, and levels of evidence. Outcomes and levels of evidence were evaluated and compared for commercially funded studies versus those that were not commercially funded.\n Twenty-three studies were included; 16 (70%) were commercially funded. Pooled clinical outcome measures data were not significantly different (Lysholm, Modified Cincinnati, patient-reported Cincinnati, Tegner, pain Visual Analog Scale) when comparing commercially funded studies with those that were not commercially funded. However, distribution of levels of evidence was significantly lower (P = .045) for commercially funded studies.\n Reassuringly, commercial funding of ACI studies did not result in a difference in published clinical outcomes versus those that were not commercially funded. However, the lower levels of evidence of commercially funded studies suggests that commercially funded ACI studies may be of less value to surgeons desiring to practice evidence-based medicine, and, in the future, commercial entities funding medical research could selectively fund studies of the highest levels of evidence.", "There is disagreement but few objective data on the relative quality of publicly or privately funded research. Cochrane reviews of randomized trials provide a good comparison opportunity because there is widespread agreement on how trial quality should be assessed and the Cochrane reviewers routinely do this.\n To compare the quality of publicly or privately funded randomized controlled trials.\n A total of 105 trials included in two Cochrane reviews were studied. Their quality assessments were abstracted from the relevant review and information about their funding source was collected from the original trial publications.\n Funding information was obtained for 87 trials. Of these, trials funded by pharmaceutical companies were larger (median sample size 126 vs. 45, P<0.001), more likely to have avoided ascertainment bias 11/14 vs. 15/41 (P=0.05). Non-significant trends in avoiding entry bias 19/19 vs. 35/37 and performance bias 13/22 vs. 14/48 also favoured the commercial trials. Commercial trials also had higher recorded attrition rates (median 6% vs. 1%, P=0.007), but this difference was entirely caused by more non-commercial trials reporting a zero attrition rate.\n The apparently lower attrition rate in the non-commercial trials should be interpreted with caution. Zero attrition in clinical trials with follow-up of many months is somewhat implausible.\n Commercially funded randomized trials tend to be of higher methodological quality than government-funded ones.\n © 2010 Blackwell Publishing Ltd.", "Bias from funding sources of trials would threaten their validity. Meta-analyses of high quality acute pain and migraine trials were used to explore the hypothesis that industry funding of clinical trials produced more favourable results than non-profit sponsorship. Analyses were planned to evaluate whether industry-sponsored trials had different results from trials funded by academic or other non-profit sources, but of 176 trials, only two were supported by non-profit sources, while 31 provided no statement of support. An alternative method is proposed within industry-sponsored trials, looking at conflicting industry interests for the same drug, used either as test or comparator treatment. Fifty-three trials used an analgesic as test and 90 as comparator, allowing comparisons to be made for aspirin 600/650 mg, ibuprofen 400 mg, paracetamol (acetaminophen) 1000 mg, rofecoxib 50 mg and sumatriptan 50 and 100 mg. Only for sumatriptan 50 and 100 mg, with the outcome of headache response at 2 h, was there any significant difference between the drug used as a test or as a comparator. The direction was for higher (worse) NNTs with sumatriptan as comparator. Investigating potential industry bias through the funding source of trials is unlikely to be adequate because of a dearth of trials funded by non-profit organisations. We propose a method based on potential conflict of interest within industry-sponsored trials. Using this method, established clinical trial results in acute pain and migraine appear to be unbiased.", "To evaluate quantitatively articles that compared effects of second and third generation oral contraceptives on risk of venous thrombosis.\n Meta-analysis.\n Cohort and case-control studies assessing risk of venous thromboembolism among women using oral contraceptives before October 1995.\n Pooled adjusted odds ratios calculated by a general variance based random effects method. When possible, two by two tables were extracted and combined by the Mantel-Haenszel method.\n The overall adjusted odds ratio for third versus second generation oral contraceptives was 1.7 (95% confidence interval 1.4 to 2.0; seven studies). Similar risks were found when oral contraceptives containing desogestrel or gestodene were compared with those containing levonorgestrel. Among first time users, the odds ratio for third versus second generation preparations was 3.1 (2.0 to 4.6; four studies). The odds ratio was 2.5 (1.6 to 4.1; five studies) for short term users compared with 2.0 (1.4 to 2.7; five studies) for longer term users. The odds ratio was 1.3 (1.0 to 1.7) in studies funded by the pharmaceutical industry and 2.3 (1.7 to 3.2) in other studies. Differences in age and certainty of diagnosis of venous thrombosis did not affect the results.\n This meta-analysis supports the view that third generation oral contraceptives are associated with an increased risk of venous thrombosis compared with second generation oral contraceptives. The increase cannot be explained by several potential biases.", "Although there is a consensus that clozapine is more effective than conventional antipsychotic drugs for treatment-resistant schizophrenia, there is great heterogeneity among results of relevant trials.\n To re-evaluate the evidence comparing clozapine with conventional antipsychotics and to investigate sources of heterogeneity.\n Individual studies were inspected with assessment of clinical relevance of results. Meta-regression analysis was performed to investigate sources of heterogeneity.\n Ten trials were examined. Recent large-scale studies have not found a substantial advantage for clozapine, especially in terms of a clinically relevant effect. Meta-regression showed that shorter study duration, financial support from a drug company and higher baseline symptom score consistently predicted greater advantage of clozapine.\n It may be inappropriate to combine studies in meta-analysis, given the degree of heterogeneity between their findings. The benefits of clozapine compared with conventional treatment may not be substantial.", "To investigate the relationship between industry- vs nonindustry-funded publications comparing the efficacy of topical prostaglandin analogs by evaluating the correspondence between the statistical significance of the publication's main outcome measure and its abstract conclusions.\n Retrospective, observational cohort study.\n English publications comparing the ocular hypotensive efficacy between any or all of latanoprost, travoprost, and bimatoprost were searched from the MEDLINE database. Each article was reviewed by three independent observers and was evaluated for source of funding, study quality, statistically significant main outcome measure, correspondence between results of main outcome measure and abstract conclusion, number of intraocular pressure outcomes compared, and journal impact factor. Funding was determined by published disclosure or, in cases of no documented disclosure, the corresponding author was contacted directly to confirm industry funding. Discrepancies were resolved by consensus. The main outcome measure was correspondence between abstract conclusion and reported statistical significance of the publications' main outcome measure.\n Thirty-nine publications were included, of which 29 were industry funded and 10 were nonindustry funded. The published abstract conclusion was not consistent with the results of the main outcome measure in 18 (62%) of 29 of the industry-funded studies compared with zero (0%) of 10 of the nonindustry-funded studies (P = .0006). Twenty-six (90%) of the industry-funded studies had proindustry abstract conclusions.\n Twenty-four percent of the industry-funded publications had a statistically significant main outcome measure; however, 90% of the industry-funded studies had proindustry abstract conclusions. Both readers and reviewers should scrutinize publications carefully to ensure that data support the authors' conclusions.", "Pharmaceutical industry funding of psychiatric research has increased significantly in recent decades, raising the question of a relationship between pharmaceutical company funding of clinical psychiatric studies and the outcomes of those studies. This study examines this relationship.\n Abstracts of articles from 1992 and 2002 in four peer-reviewed psychiatric journals were examined. Drug outcomes (n=542) for clinical studies were evaluated and then compared across sponsorship source. Outcome raters were blind to source of sponsorship. The percentage of these studies sponsored by drug companies in 2002 v. 1992 was also compared. In a secondary analysis, the contribution of a series of potentially mediating variables to the relationship between sponsorship source and study outcome was assessed via logistic regression.\n The percentage of studies sponsored by drug companies increased from 25% in 1992 to 57% in 2002. Favorable outcomes were significantly more common in studies sponsored by the drug manufacturer (78%) than in studies without industry sponsorship (48%) or sponsored by a competitor (28%). These relationships remained after controlling for the effects of journal, year, drug studied, time since FDA drug approval, diagnosis, sample size, and selected study design variables.\n These data indicate an association between pharmaceutical industry funding of clinical studies and positive outcomes of those studies. Further research is needed to elucidate the mechanisms underlying this relationship.", "The goal was to assess the risk of bias among pediatric, randomized, controlled trials (RCTs) reported in 8 high-impact journals.\n We searched PubMed for all pediatric RCTs reported between July 1, 2007, and June 30, 2008, in 8 journals with high impact factors. Using Cochrane Collaboration methods for risk assessment, we evaluated all reports for risk of bias according to domain (ie, randomized sequence generation, allocation concealment, masking, incomplete outcome data, selective outcome reporting, and other). We used multiple logistic regression to test for associations between the presence of a high risk of bias according to domain and funding source, intervention type, trial registration, and multicenter status.\n Industry-funded RCTs were more likely to show a high risk of bias for sequence generation, compared with government-funded RCTs (adjusted odds ratio [aOR]: 6.1 [95% confidence interval [CI]: 1.70- 21.89]), and behavioral/educational trials were more likely to show a high risk of bias for sequence generation (aOR: 2.8 [95% CI: 1.06-7.36]) and allocation concealment (aOR: 4.09 [95% CI: 1.69-9.90]), compared with drug trials. Registered trials were less likely to have a high risk of bias for sequence generation, compared with nonregistered trials (aOR: 0.33 [95% CI: 0.15-0.71]).\n Overall, we found a large proportion of pediatric RCT reports with a high risk of bias for sequence generation and allocation concealment. Factors associated with a high risk of bias included industry funding and assessment of behavioral/educational interventions, whereas trial registration was associated with a lower risk of bias.", "To compare the quality, relevance, and structure of drug studies published in symposium proceedings that are sponsored by drug companies with 1) articles from symposia with other sponsors and 2) articles in the peer-reviewed parent journals of symposium proceedings; and to study the relation between drug company sponsorship and study outcome.\n Cross-sectional studies of clinical drug studies published in symposium proceedings or their parent medical journals.\n The proportion of articles with no methods sections (which are necessary to assess quality); methodologic quality and clinical relevance scores; and the proportion of articles with outcomes favoring the drug of interest.\n Symposia sponsored by single drug companies had more articles without methods sections (10%; 108 of 1064) than did symposia that had other sponsors (3%; 58 of 2314) or symposia that had no mentioned sponsor (2%; 29 of 1663) (P < 0.001). The mean methodologic quality and relevance scores of articles were similar both by type of sponsorship and between articles published in symposia sponsored by single drug companies and articles from the parent journals. Significantly more articles with drug company support (98%; 39 of 40) than without drug company support (79%; 89 of 112) had outcomes favoring the drug of interest (P = 0.01).\n Articles in symposia sponsored by single drug companies were similar in quality and clinical relevance to articles with other sponsors and to articles published in the parent journals. Articles with drug company support are more likely than articles without drug company support to have outcomes favoring the drug of interest.", "This study presents a meta-analysis of the influence of several potentially biasing factors (eg industry support, extrapyramidal side effects) on efficacy of studies comparing second-generation antipsychotic (SGA) with first-generation antipsychotic (FGA) medications. We used the dataset from our previously published meta-analysis of 124 randomized controlled trials (RCTs) comparing SGAs with FGAs, to evaluate whether certain possible biases could influence the actual outcome on the total score of the Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impressions (CGI) scores. Industry sponsorship was determined by contact with authors or publication statement. We calculated whether (1) industry sponsorship, (2) study quality, (3) extrapyramidal symptoms (EPS) properties, or (4) prophylactic antiparkinsonian medications influenced SGA vs FGA efficacy for each drug and averaged overall by two Hedges and Olkin-based meta-analyses. The analysis found that none of the factors was significantly associated with a particular outcome. While industry-sponsored articles may conclude their medication to be more favorable than that of a competitor in an RCT, we found that the observed efficacy was not influenced by sponsorship. Many attribute the finding that SGAs appears to be more efficacious than FGAs to be a result of EPS-decreasing efficacy (or its measurement). We were unable to confirm that the drug's EPS properties or antiparkinsonian management altered actual efficacy.", "Clinical trial registries are in widespread use to promote transparency around trials and their results.\n To describe characteristics of drug trials listed in ClinicalTrials.gov and examine whether the funding source of these trials is associated with favorable published outcomes.\n An observational study of safety and efficacy trials for anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators conducted between 2000 and 2006.\n ClinicalTrials.gov, a Web-based registry of clinical trials launched in 1999.\n Publications resulting from the trials for the 5 drug categories of interest were identified, and data were abstracted on the trial record and publication, including timing of registration, elements of the study design, funding source, publication date, and study outcomes. Assessments were based on the primary funding categories of industry, government agencies, and nonprofit or nonfederal organizations.\n Among 546 drug trials, 346 (63%) were primarily funded by industry, 74 (14%) by government sources, and 126 (23%) by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or nonfederal organization-funded trials (P < 0.001). Trials funded by nonprofit or nonfederal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs. 61.2%; P = 0.013). Rates of trial publication within 24 months of study completion ranged from 32.4% among industry-funded trials to 56.2% among nonprofit or nonfederal organization-funded trials without industry contributions (P = 0.005 across groups).\n The publication status of a trial could not always be confirmed, which could result in misclassification. Additional information on study protocols and comprehensive trial results were not available to further explore underlying factors for the association between funding source and outcome reporting.\n In this sample of registered drug trials, those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources.\n National Library of Medicine and National Institute of Child Health and Human Development, National Institutes of Health.", "In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome.\n The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug.\n Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings.\n Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies.", "A publication bias exists towards positive results in studies funded by pharmaceutical companies.\n To determine whether drug studies in the pulmonary/allergy literature also demonstrate a publication bias towards more favorable results when a pharmaceutical company funds the study.\n We reviewed all original articles published in seven pulmonary and allergy journals between October 2002 and September 2003. Included in the review were studies of inhaled corticosteroids (oral or nasal), long- or short-acting bronchodilators, or leukotriene receptor antagonists. Articles with funding from a pharmaceutical company and/or one or more authors employed by a pharmaceutical company were considered pharmaceutical company-sponsored studies. The remaining studies were considered not sponsored by a pharmaceutical company. Results were compared to ascertain whether positive results were obtained more frequently in the company-sponsored studies.\n Of the 100 articles included in this review 63 were considered pharmaceutical company-sponsored research. Results favorable for the drugs studies were significantly more common in those funded by a pharmaceutical company (98% vs. 32%).\n In the pulmonary and allergy literature, as in other fields, there is a publication bias towards positive results in pharmaceutical company-sponsored research.", "To explore the relation between study concordance, take home message, funding, and dissemination of comparative studies assessing the effects of influenza vaccines.\n Systematic review without meta-analysis.\n Search of the Cochrane Library, PubMed, Embase, and the web, without language restriction, for any studies comparing the effects of influenza vaccines against placebo or no intervention. Abstraction and assessment of quality of methods were carried out.\n We identified 259 primary studies (274 datasets). Higher quality studies were significantly more likely to show concordance between data presented and conclusions (odds ratio 16.35, 95% confidence interval 4.24 to 63.04) and less likely to favour effectiveness of vaccines (0.04, 0.02 to 0.09). Government funded studies were less likely to have conclusions favouring the vaccines (0.45, 0.26 to 0.90). A higher mean journal impact factor was associated with complete or partial industry funding compared with government or private funding and no funding (differences between means 5.04). Study size was not associated with concordance, content of take home message, funding, and study quality. Higher citation index factor was associated with partial or complete industry funding. This was sensitive to the exclusion from the analysis of studies with undeclared funding.\n Publication in prestigious journals is associated with partial or total industry funding, and this association is not explained by study quality or size.", "Registration of clinical trials has been introduced largely to reduce bias toward statistically significant results in the trial literature. Doubts remain about whether advance registration alone is an adequate measure to reduce selective publication, selective outcome reporting, and biased design. One of the first areas of medicine in which registration was widely adopted was oncology, although the bulk of registered oncology trials remain unpublished. The net influence of registration on the literature remains untested. This study compares the prevalence of favorable results and conclusions among published reports of registered and unregistered randomized controlled trials of new oncology drugs.\n We conducted a cross-sectional study of published original research articles reporting clinical trials evaluating the efficacy of drugs newly approved for antimalignancy indications by the United States Food and Drug Administration (FDA) from 2000 through 2005. Drugs receiving first-time approval for indications in oncology were identified using the FDA web site and Thomson Centerwatch. Relevant trial reports were identified using PubMed and the Cochrane Library. Evidence of advance trial registration was obtained by a search of clinicaltrials.gov, WHO, ISRCTN, NCI-PDQ trial databases and corporate trial registries, as well as articles themselves. Data on blinding, results for primary outcomes, and author conclusions were extracted independently by two coders. Univariate and multivariate logistic regression identified associations between favorable results and conclusions and independent variables including advance registration, study design characteristics, and industry sponsorship.\n Of 137 original research reports from 115 distinct randomized trials assessing 25 newly approved drugs for treating cancer, the 54 publications describing data from trials registered prior to publication were as likely to report statistically significant efficacy results and reach conclusions favoring the test drug (for results, OR = 1.77; 95% CI = 0.87 to 3.61) as reports of trials not registered in advance. In multivariate analysis, reports of prior registered trials were again as likely to favor the test drug (OR = 1.29; 95% CI = 0.54 to 3.08); large sample sizes and surrogate outcome measures were statistically significant predictors of favorable efficacy results at p < 0.05. Subgroup analysis of the main reports from each trial (n = 115) similarly indicated that registered trials were as likely to report results favoring the test drug as trials not registered in advance (OR = 1.11; 95% CI = 0.44 to 2.80), and also that large trials and trials with nonstringent blinding were significantly more likely to report results favoring the test drug.\n Trial registration alone, without a requirement for full reporting of research results, does not appear to reduce a bias toward results and conclusions favoring new drugs in the clinical trials literature. Our findings support the inclusion of full results reporting in trial registers, as well as protocols to allow assessment of whether results have been completely reported.", "The objective of this study was to determine the effect of industry bias in a systematically reviewed body of evidence of head-to-head trials.\n We limited our analysis to published head-to-head randomized controlled trials of selective serotonin reuptake inhibitors (SSRIs) identified in a comparative effectiveness review. Two reviewers independently determined the status of funding for each trial. We classified drugs into one of two groups: (1) drugs associated with the funding source and (2) drugs not associated with the funding source. To determine the effect of any underlying industry bias, we conducted relative-benefit meta-analyses comparing the response rates of drugs when associated with the funding source with response rates of the same drugs when not associated with the funding source.\n Thirteen out of 20 studies (65%) numerically favored drugs associated with the funding source over drugs used as controls. The pooled response rates of SSRIs, when associated with the funding source, are significantly greater than those of the same SSRIs when not associated with the sponsor (relative benefit=1.07; 95% confidence interval=1.02-1.11). The difference, however, is likely to be not of clinical importance.\n The effect of industry bias in comparative effectiveness reviews might play a lesser role than in systematic reviews of placebo-controlled trials.\n Copyright 2010 Elsevier Inc. All rights reserved.", "Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings. In this study, we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials.\n We examined a consecutive series of 332 randomized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals. Each eligible study was independently reviewed for methodological quality using a 21-point index with 5 domains: randomization, outcomes, eligibility criteria, interventions and statistical issues. Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant. For studies that did not explicitly identify a primary outcome, we defined a \"positive\" study as one with at least 1 statistically significant outcome measure. We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results, while controlling for study quality and sample size.\n Among the 332 randomized trials, there were 158 drug trials, 87 surgical trials and 87 trials of other therapies. In 122 (37%) of the trials, authors declared industry funding. An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.3-3.5). The association remained significant after adjustment for study quality and sample size (adjusted OR 1.8, 95% CI 1.1-3.0). There was a nonsignificant difference between surgical trials (OR 8.0, 95% CI 1.1-53.2) and drug trials (OR 1.6, 95% CI 1.1-2.8), both of which were likely to have a pro-industry result (relative OR 5.0, 95% CI 0.7-37.5, p = 0.14).\n Industry-funded trials are more likely to be associated with statistically significant pro-industry findings, both in medical trials and surgical interventions.", "Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions.\n To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events.\n Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication).\n Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not.\n The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events.\n Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data.", "To assess the association between competing interests and authors' conclusions in randomised clinical trials.\n Epidemiological study of randomised clinical trials published in the BMJ from January 1997 to June 2001. Financial competing interests were defined as funding by for profit organisations and other competing interests as personal, academic, or political. Studies: 159 trials from 12 medical specialties.\n Authors' conclusions defined as interpretation of extent to which overall results favoured experimental intervention. Conclusions appraised on 6 point scale; higher scores favour experimental intervention.\n Authors' conclusions were significantly more positive towards the experimental intervention in trials funded by for profit organisations alone compared with trials without competing interests (mean difference 0.48 (SE 0.13), P=0.014), trials funded by both for profit and non-profit organisations (0.30 (SE 0.10), P=0.003), and trials with other competing interests (0.45 (SE 0.13), P=0.006). Other competing interests and funding from both for profit and non-profit organisations were not significantly associated with authors' conclusions. The association between financial competing interests and authors' conclusions was not explained by methodological quality, statistical power, type of experimental intervention (pharmacological or non-pharmacological), type of control intervention (for example, placebo or active drug), or medical specialty.\n Authors' conclusions in randomised clinical trials significantly favoured experimental interventions if financial competing interests were declared. Other competing interests were not significantly associated with authors' conclusions.", "In surveys based on data available prior to 2000, clinical trials funded by for-profit organizations appeared more likely to report positive findings than those funded by not-for-profit organizations. Whether this situation has changed over the past 5 years or whether similar effects are present among jointly funded trials is unknown.\n To determine in contemporary randomized cardiovascular trials the association between funding source and the likelihood of reporting positive findings.\n We reviewed 324 consecutive superiority trials of cardiovascular medicine published between January 1, 2000, and July 30, 2005, in JAMA, The Lancet, and the New England Journal of Medicine.\n The proportion of trials favoring newer treatments over the standard of care was evaluated by funding source.\n Of the 324 superiority trials, 21 cited no funding source. Of the 104 trials funded solely by not-for-profit organizations, 51 (49%) reported evidence significantly favoring newer treatments over the standard of care, whereas 53 (51%) did not (P = .80). By contrast, 92 (67.2%) of 137 trials funded solely by for-profit organizations favored newer treatments over standard of care (P<.001). Among 62 jointly funded trials, 35 (56.5%), an intermediate proportion, favored newer treatments. For 205 randomized trials evaluating drugs, the proportions favoring newer treatments were 39.5%, not-for-profit; 54.4%, jointly funded; and 65.5%, for-profit trials (P for trend across groups = .002). For the 39 randomized trials evaluating cardiovascular devices, the proportions favoring newer treatments were 50.0%, not-for-profit; 69.2%, jointly funded; and 82.4%, for-profit trials (P for trend across groups = .07). Regardless of funding source, trials using surrogate end points, such as quantitative angiography, intravascular ultrasound, plasma biomarkers, and functional measures were more likely to report positive findings (67%) than trials using clinical end points (54.1%; P = .02).\n Recent cardiovascular trials funded by for-profit organizations are more likely to report positive findings than trials funded by not-for-profit organizations, as are trials using surrogate rather than clinical end points. Trials jointly funded by not-for-profit and for-profit organizations appear to report positive findings at a rate approximately midway between rates observed in trials supported solely by one or the other of these entities.", "When a sponsor funds a study of two competing drugs in a head-to-head comparison, the results and conclusions are likely to favor the sponsor's drug. Thiazolidinediones, oral medications used for the treatment of type 2 diabetes, are one of the most costly choices of oral anti-diabetic medications, yet they do not demonstrate clinically relevant differences in achieving lower glycosylated hemoglobin levels compared to other oral antidiabetic drugs. Our aim is to examine associations between research funding source, study design characteristics aimed at reducing bias, and other factors with the results and conclusions of randomized controlled trials (RCTs) of thiazolidinediones compared to other oral hypoglycemic agents.\n This is a cross-sectional study of 61 published RCTs comparing a thiazolidinedione (glitazone) to another anti-diabetic drug or placebo for treatment of type 2 diabetes. Data on study design characteristics, funding source, author's financial ties, results for primary outcomes, and author conclusions were extracted. Univariate logistic regression identified associations between independent variables and results and conclusions that favored the glitazone. Of the RCTs, 59% (36/61) were funded by industry, 39% (24/61) did not disclose any funding. Common study design weaknesses included inadequate blinding and lack of concealment of allocation. Trials that reported favorable glycemic control results for the glitazone were more likely to have adequate blinding (OR (95% CI) = 5.42 (1.46, 21.19), p = 0.008) and have a corresponding author with financial ties to the glitazone manufacturer (OR (95% CI) = 4.12 (1.05, 19.53); p = 0.04). Trials with conclusions favoring the glitazone were less likely to be funded by a comparator drug company than a glitazone company (OR (95% CI) = 0.026 (0, 0.40), p = 0.003) and less likely to be published in journals with higher impact factors (OR (95% CI) = 0.79 (0.62, 0.97), p = 0.011). One limitation of our study is that we categorized studies as funded by industry based on each article's disclosure which could underestimate the number of industry sponsored studies and personal ties of investigators. Additionally, our study did not include any head-to-head comparisons of one glitazone to another.\n Published RCT comparisons of glitazones with other anti-diabetic drugs or placebo are predominantly industry supported and this support, as well as the financial ties of study authors, appears to be associated with favorable findings.", "There is uncertainty about the contribution of specific pharmacological properties to the efficacy of antidepressants.\n To assess whether specific pharmacological characteristics of alternative antidepressants resulted in altered efficacy compared to that of selective serotonin reuptake inhibitors in the treatment of major depression.\n Meta-regression analysis of randomised trials that compare treatment with a selective serotonin reuptake inhibitor and an alternative antidepressant.\n One-hundred-and-five randomised trials were included. None of the factors identified a priori predicted a statistically significant improvement in outcome across the trials.\n This analysis does not provide evidence that antidepressants acting at more than one pharmacological site differ in efficacy from drugs selective for serotonin reuptake in the treatment of major depression.", "Evidence regarding the safety profile of drugs may vary depending on study sponsorship. We aimed to evaluate differences between studies funded by the pharmaceutical manufacturer of the drug (PF) and those with no pharmaceutical funding (NoPF) regarding the finding and interpretation of adverse effects of inhaled corticosteroids.\n We assessed the safety reporting of inhaled corticosteroids in 275 PF and 229 NoPF studies identified by a MEDLINE search using prespecified criteria.\n Overall, the finding of statistically significant differences for adverse effects was significantly less frequent in PF (34.5%) than in NoPF (65.1%) studies (prevalence ratio, 0.53; 95% confidence interval, 0.44-0.64). This association became nonsignificant (prevalence ratio, 0.94; 95% confidence interval, 0.77-1.15) after controlling for design features (such as dose or use of parallel groups) that tended to be associated with less frequent finding of adverse effects and were more common in PF studies. Among studies finding a statistically significant increase in adverse effects associated with the study drug, the authors of PF articles concluded that the drug was \"safe\" more frequently than the authors of NoPF studies (prevalence ratio, 3.68; 95% confidence interval, 2.14-6.33).\n The type of funding may have determinant effects on the design of studies and on the interpretation of findings: funding by the industry is associated with design features less likely to lead to finding statistically significant adverse effects and with a more favorable clinical interpretation of such findings. Disclosure of conflicts of interest should be strengthened for a more balanced opinion on the safety of drugs.", "Randomized controlled trials (RCTs) of interventions provide the highest level of evidence about efficacy but their value either alone or within a meta-analysis is dependent on its methodological quality. For this reason recent RCTs in organ transplantation were assessed for quality. RCTs published between 2004 and 2006 (n = 332) were assessed, after excluding duplicate and nonEnglish reports. Quality was evaluated using the Jadad score plus allocation concealment and intention to treat analysis. We noted journal type, journal author instructions, funding source, sample size and number and location of study centres. Around one-third of RCTs had a Jadad score of 3 or greater (indication of a methodologically good quality trial) and the other two parameters were satisfied in just over one third. Although the majority of trials were published in speciality journals the quality of those published in general journals was superior. Commercially sponsored trials were of better quality as were multicentre trials in contrast to single centre trials. Overall quality of reporting of RCTs in organ transplantation is poor and as RCTs provide the highest level of evidence in evaluations of interventions there needs to be a concerted effort within the transplant community to improve the standards of RCTs.", "The reporting quality of randomized controlled trials (RCTs) is poor in general medicine and several areas of specialization but unknown in endocrinology.\n Our aim was to assess the reporting quality of RCTs in general endocrinology. A secondary objective was to identify predictors for better reporting quality.\n We systematically reviewed RCTs published in three general endocrinology journals between January 2005 and December 2006.\n We included parallel-design RCTs that addressed a question of treatment or prevention. Article selection and data abstraction were conducted by two reviewers independently, and disagreements were resolved by consensus.\n There were two main outcomes: 1) a 15-point overall reporting quality score (OQS) based on the Consolidated Standards for Reporting Trials (CONSORT); and 2) a 3-point key score, based on allocation concealment, blinding, and use of intention-to-treat analysis.\n Eighty nine RCTs were included. The median OQS was 10 (interquartile range = 2). Allocation concealment, blinding, and analysis by intention to treat were reported in 10, 20, and 16 of the 89 RCTs, respectively. A multivariable regression analysis showed that complete industrial funding [incidence rate ratio (IRR) = 1.014; 95% confidence interval (CI), 1.010-1.018], journal of publication (IRR = 1.068; 95% CI, 1.007-1.132), and sample size (IRR = 1.048; 95% CI, 1.026-1.070) were significantly associated with a slightly better OQS.\n The quality of RCT reporting in general endocrine literature is suboptimal. We discuss our results, highlight the areas where improvements are needed, and provide some recommendations.", "Studies of drug treatments are more likely to report favourable outcomes when they are funded by the pharmaceutical industry. We compared drug trials reported in three major psychiatric journals to investigate these influences. Independent studies were more likely to report negative findings than industry-funded studies. However, the involvement of a drug company employee had a much greater effect on study outcome than financial sponsorship alone.", "To assess the published research base for interventions for osteoarthritis of the knee, and to identify areas in need of further research.\n Literature searches were conducted on electronic databases (Medline, Embase, ISI, and Cochrane library), bibliographies of existing review articles were hand searched, and a postal questionnaire was sent to members of the Osteoarthritis Research Society International. All relevant articles were copied and searched for treatment type, study methodology, statistical results, conclusions, funding source, researcher affiliations, and year of publication, using a predetermined data extraction form.\n There have been marked changes in the literature over the period studied (1950-98), with a recent rise in trials of physical therapy, educational interventions, and complementary treatments. However, overall, most research was either drug (59.1%) or surgically (25.6%) related. Most of the studies reported positive results (94%). Research on oral drugs was significantly more likely to provide a positive result than research on any other intervention (p<0.001 by chi(2) test). Commercially funded studies were significantly more likely to produce a positive result than non-commercially funded research (p=0.0027 by chi(2) test).\n Analysis of time trends indicates that the research agenda does shadow changes in consumer demands. However, there are significant gaps in the research base that need to be considered.", "Financial and other competing interests have recently received increasing attention. In particular clinical research in plastic surgery attracts for-profit organizations, thus, explaining the increasing number of financial sponsorships. However, research articles often lack sufficient description of study design as well as disclosure of the source of funding. Furthermore, debate exists whether industry funding influences research findings and is leading to pro-industry results. A hand search was conducted identifying all randomized controlled (RCT) and controlled clinical trials (CCT) in 4 plastic surgery journals (Plastic and Reconstructive Surgery, British Journal of Plastic Surgery, Annals of Plastic Surgery, and Aesthetic Plastic Surgery) between 1990 and 2005. Subsequently, the influence of financial support on study outcome was analyzed. A total of 10,476 original articles were analyzed, resulting in the identification of 346 clinical trials which meet the Cochrane criteria for RCTs and CCTs. One hundred eighty-three trials and 163 studies were found to be RCTs and CCTs, respectively. Hereof, only 70 trials (20.2%) reported on grant support. Of these, 42 trials (60%) were supported by the industry. Depending on the topic addressed marked differences were detected regarding grant support. Studies with a focus on reconstructive plastic surgery were supported by the industry and by public institutions in almost equal shares (18 trials vs. 15 trials), whereas aesthetic surgical topics were predominantly funded by the industry (13 trials vs. 6 trials). Industry-funded trials reported more often statistically significant differences between treatment arms (28 trials vs. 16 trials). Authors' conclusions were found to be positively associated with financial competing interests. However, trial funding is rarely declared in the plastic surgery literature. Thus, the quality of reporting needs to be improved to be able to investigate these relationships in greater detail and draw more representative conclusions.", "The pharmaceutical industry has become a major source of funding for biomedical research. Our general observation is that pharmaceutical industry employees are appearing with increasing frequency as coauthors of clinical trial publications.\n To characterize clinical trial funding, reporting, and sources; investigate author-industry affiliation; and describe clinical outcome trends over time.\n We reviewed 500 randomly selected clinical trials published in 5 influential medical journals over a 20-year period (1981-2000).\n Of the 500 clinical trials reviewed, 181 (36%) involved pharmaceutical industry as an independent (n = 104) or joint (n = 77) sponsor and 180 (36%) involved a peer-review funding source; the balance (139; 28%) lacked any declared sponsorship. The percentage of industry-sponsored clinical trials increased to 62% during 1997-2000. The percentage of nonprofit sponsored clinical trials remained constant over time, while the percentage of those without funding declaration declined. Reported author affiliation with industry increased to 66% of clinical trials sponsored only by industry. An increase in the percentage of clinical trials with reported author-industry affiliation was observed for all journals. Regardless of funding source, the majority of clinical trials reported clinical outcomes that favored the study drug.\n Pharmaceutical industry-sponsored and mixed-funding clinical trials are common, and the relative incidence of published trials with these declared funding sources in the 5 journals reviewed has increased. Industry employees are appearing as coauthors of clinical trial publications with increasing frequency.", "The effect of funding source on the outcome of randomized controlled trials has been investigated in several medical disciplines; however, psychiatry has been largely excluded from such analyses. In this article, randomized controlled trials of second generation antipsychotics in schizophrenia are reviewed and analyzed with respect to funding source (industry vs. non-industry funding).\n A literature search was conducted for randomized, double-blind trials in which at least one of the tested treatments was a second generation antipsychotic. In each study, design quality and study outcome were assessed quantitatively according to rating scales. Mean quality and outcome scores were compared in the industry-funded studies and non-industry-funded studies. An analysis of the primary author's affiliation with industry was similarly performed.\n Results of industry-funded studies significantly favored second generation over first generation antipsychotics when compared to non-industry-funded studies. Non-industry-funded studies showed a trend toward higher quality than industry-funded studies; however, the difference between the two was not significant. Also, within the industry-funded studies, outcomes of trials involving first authors employed by industry sponsors demonstrated a trend toward second generation over first generation antipsychotics to a greater degree than did trials involving first authors employed outside the industry (p=0.05).\n While the retrospective design of the study limits the strength of the findings, the data suggest that industry bias may occur in randomized controlled trials in schizophrenia. There appears to be several sources by which bias may enter clinical research, including trial design, control of data analysis and multiplicity/redundancy of trials." ]

[ "850563", "7018166", "7282312", "780062", "6575576", "472913", "367426", "6575575", "3326393", "333516", "338022", "3165111", "4842660", "3250183", "7023173", "42577" ]

[ "Early labor initiation with oral PGE2 after premature rupture of the membranes at term.", "Stimulation of labor in cases of premature rupture of the membranes at or near term. A consecutive randomized study of prostaglandin E2-tablets and intravenous oxytocin.", "Induction of labor with oral prostaglandin E2 and buccal demoxytocin without amniotomy.", "A randomised controlled trial of an oral solution of prostaglandin E2 and oral oxytocin used immediately after low amniotomy for induction of labour in the presence of a favourable cervix.", "Use of oral oxytocics for stimulation of labor in cases of premature rupture of the membranes at term. A randomized comparative study of prostaglandin E2 tablets and demoxytocin resoriblets.", "Oral and intravaginal prostaglandin E2 for cervical ripening and induction of labour.", "A comparison of four methods of ripening the unfavourable cervix.", "Oral oxytocics for induction of labor. A randomized study of prostaglandin E2 tablets and demoxytocin resoriblets.", "Induction of labor and cervical ripening with oral PGE2 in risk pregnancies. A placebo-controlled study.", "Uterine priming with oral prostaglandin E2 prior to elective induction with oxytocin.", "Intravenous oxytocin and oral prostaglandin E2 for ripening of the unfavourable cervix.", "A comparison of oral and intracervical prostaglandin E2 for ripening of the unfavourable cervix prior to induction of labour.", "A comparison between intravenous oxytocin and oral prostaglandin E2 for the induction of labour in parous patients.", "A comparison of oral prostaglandin E2 tablets with intravenous oxytocin for stimulation of labor after premature rupture of membranes at term.", "Induction of labor with and without primary amniotomy. A randomized study of prostaglandin E2 tablets and intravenous oxytocin.", "A comparative study of labor induced by oral prostaglandin E2 and buccal tablets of demoxytocin." ]

[ "Two groups of healthy women at term, who were not in labor 3 hours after premature rupture of the membranes, were studied. In one group labor induction with oral prostaglandin E2 (PGE2) was begun 3 hours after rupture, and in the other group intravenous oxytocin induction was begun 12 hours after rupture. PGE2 was successful in initiating active labor in 88% of women treated. Of the women who were observed for 12 hours, one-half began labor spontaneously during that time. Women in whom labor was induced with PGE2 given 3 hours after rupture of the membranes had a shorter interval of rupture to delivery, a lower cesarean section rate, and shorter postpartum hospitalization. Although significant bradycardia did not occur in fetuses of those women given PGE2, 10% of infants whose mothers were receiving oxytocin were delivered by cesarean section for this reason. It is concluded that oral PGE2 is safe and effective for induction of labor in women with premature membrane rupture. The benefits, to both mother and fetus, of a shorter latent period are discussed.", "Prostaglandin E2-tablets were compared to intravenous oxytocin for the stimulation of labor in 201 patients at or near term, with premature spontaneous rupture of the membranes without labor activity for 6 hours after the escape of fluid. The patients were randomly allocated; 99 were treated with PGE2-tablets (0.5-1.5 mg/hr) and 102 with intravenous oxytocin (7.5-45 mIU/min). The treatment was ineffective in the PGE2 group in 3 cases; these were treated successfully with intravenous oxytocin. In the oxytocin group, 3 patients were delivered by cesarean section for reasons not associated with the drug. A significant difference was found in the stimulation-delivery time, in favor of intravenous oxytocin. Although PGE2 tablets are a safe and convenient alternative to intravenous oxytocin, the investigation showed that intravenous oxytocin is preferable in cases of premature rupture of the membranes with more than 6 hours without labor activity.", "The results of labor induction without primary amniotomy in 132 primi-parae are presented. Prostaglandin E2 was given orally to 40 patients, 45 were treated buccally with demoxytocin and 47 were given a combination consisting of demoxytocin on the first day and prostaglandin E2 on the second day. All patients had Bishop scores less than 7. No significant difference in the efficiency of induction between the three types of treatment was detected. The delivery rates 48 hours after the start of treatment were 45.0 per cent, 37.8 per cent and 46.8 per cent respectively. The incidence of complications was not increased in the group which received the combined treatment.", "A randomised controlled trial was carried out in 50 primigravidae and 50 multigravidae to compare the effectiveness in induction of labour after low amniotomy of prostaglandin E2, given as an oral solution, and oxytocin, given as buccal tablets. The results showed that in dosages recommended by the manufacturers, both oxytocic preparations were almost equally effective. With oral oxytocin, once labour had been established and dosage was left to the discretion of the staff, there appeared to be a potentially dangerous tendency to continue giving large doses despite adequate uterine contractions. The authors comment that this was probably the reason why oxytocin-treated multigravidae having normal deliveries within 24 hours had labours significantly shorter on average than those of other successfully induced patients.", "The efficacy of oral PGE2 tablets and buccal demoxytocin (resoriblets) for the induction of labor in cases of premature rupture of the membranes (PROM) after the 37th week of gestation has been evaluated in a prospective, randomized investigation of 193 women. PGE2 tablets (Prostin) were given to 109 parturients and demoxytocin resoriblets (Sandopart) to 84. The former were given in increasing doses from an initial 0.5 mg to a maximum of 1.5 mg every hour. The demoxytocin was administered at a constant dosage of 50 I.U. every 30 min. The treatment was unsuccessful in 10 of the women treated with PGE2 tablets and in 19 women receiving demoxytocin resoriblets. In addition, the treatment had to be discontinued in 5 women in the PGE2 group due to gastrointestinal side effects. This gives a total success rate of 86.3% for treatment with PGE2 against 77.4% in respect of demoxytocin. This difference is not significant. No difference was observed between the two treatment groups as regards: the stimulation-delivery interval, duration of the various stages of labor, efficacy in primiparae and multiparae, efficacy in patients with a high/low Bishop score. A significantly higher frequency of gastro-intestinal side effects was seen in those treated with PGE2 (21.7%) as compared with demoxytocin (3.6%). The frequency of surgical intervention was 17% in the PGE2 group and 10% in the demoxytocin group. In 4 cases where the stimulation was successful, cesarean section was carried out for reasons unrelated to the drug therapy. Despite the fact that demoxytocin treatment results in fewer side effects than PGE2, the efficacy of the drug is not superior. Based on experience from previous investigations carried out in this department, where intravenous oxytocin was found to be clearly better than oral PGE2 for the induction of labor in cases of PROM, intravenous oxytocin will remain the method of choice due to the shorter period of treatment, which must take priority.", "The effect of prostaglandin E2 (PGE2) in 'ripening' the cervix was studied in 33 patients who required surgical induction of labour. Patients included primigravidas and parous subjects between 36 and 42 weeks of gestation. Sixteen patients received a total oral dose of 5 mg PGE2 and 17 received 4 - 6 mg PGE2 intravaginally in the form of a gel. There was significant improvement in 'ripeness' of the cervix in all groups, the intravaginal route giving slightly better results than the oral route. Ten patients remained unsuitable for induction because of inadequate dilatation of the cervix or a high fetal head. Four patients on oral therapy developed late decelerations of the fetal heart and 3 of these were delivered by immediate caesarean section. The implications of this and the reasons for the inability to perform inductions after 'ripening' are discussed.", "A comparison was made between four methods of ripening the unfavourable cervix (extra-amniotic prostaglandin E2 gel, oral prostaglandin E2, intravaginal prostaglandin E2 and intravenous oxytocin) in a clinical trial involving 60 primigravidae. In all groups there was an improvement in cervical status. This was significantly greater in those patients who received extra-amniotic prostaglandin gel and they also showed significant decreases in the mean induction-delivery interval and in the incidence of Caesarean section.", "A randomized comparative study of 387 consecutive patients admitted for induction of labor was carried out using two orally administered oxytocics (prostaglandin E2 tablets (Prostin) or Demoxytocin resoriblets for buccal administration (Sandopart)), the results of which are reported here. One-hundred and twenty-three cases were suitable for primary amniotomy; of these 48 were given PGE2 tablets and 75 received demoxytocin resoriblets. In a further 264 cases, primary amniotomy was inadvisable and of these, 133 patients were allotted to the PGE2 treatment group and 131 to treatment with demoxytocin. A significantly higher success rate was observed (p less than 0.05) in the PGE2 group in cases where primary amniotomy had been carried out, as compared with the demoxytocin group. Parturition was successfully induced in 82.0% of the patients given PGE2 tablets, as against only 63.4% of those receiving demoxytocin following 2 days of stimulation without primary amniotomy. This difference is statistically significant at the 0.001 level, and presumably due to the highly significant difference (p less than 0.0001) between patients with a Bishop score of 5 or less, where induction was successful in 75.4% given PGE2 tablets, in contrast to a success rate of only 36.7% in patients receiving demoxytocin resoriblets. No difference was observed in the success rate between the two treatment groups when the Bishop score was 6 or more. No difference was recorded in the incidence of fetal distress, instrumental delivery or low Apgar score between the two treatment groups. However, a higher incidence of vomiting and diarrhea were observed in patients treated with PGE2 tablets (11%) as compared with those receiving demoxytocin (1.5%). There was no difference with regard to the induction-delivery time, nor to the different stages of labor between otherwise comparable treatment groups when the induction was successful. It is concluded in respect of induction of labor using orally administered oxytocics that PGE2 (tablets) are preferable to demoxytocin (resoriblets) as it is the more effective of the two.", "A double-blind, placebo-controlled study was undertaken to evaluate the priming effect on the cervix and also the effect on the subsequent induction of labor. 0.5 mg oral PGE2 or placebo was given hourly for two 12-h periods. A total of 191 women with risk pregnancies and Bishop score less than or equal to 5 were studied. The induction of labor was carried out with oxytocin or oral PGE2 in a randomized manner. Labor was induced in 39% of the women during the PGE2 priming. The best result, 71% vaginal deliveries, was achieved with the combination of PGE2 priming and induction of labor with oxytocin.", "Fifty pregnant women at term, with a cervix unfavorable for induction, were electively induced with intravenous oxytocin after priming with either oral prostaglandin E2 or a placebo. Oral PGE2 was effective in increasing the Bishop score and in inducing labor prior to the induction, but did not increase the incidence of successful inductions.", "A clinical trial involving 60 patients was conducted to assess the relative efficacy of intravenous oxytocin and oral prostaglandin E2 in ripening the unfavourable cervix, when given as a priming dose on the day before induction of labour. There was significant improvement in the Bishop score, and the subsequent induction-delivery interval following priming with prostaglandin. This improvement appeared to be dose-related.", "nan", "nan", "Sixty-nine patients (48 primigravidae and 21 multigravidae) with 12 hours of spontaneous premature rupture of membranes (PROM) after 36 weeks gestation were randomly allocated to receive either prostaglandin E2 (PGE2) oral tablets or intravenous oxytocin to stimulate labor. The two treatments were compared regarding stimulation - delivery interval (SDI), analgesic requirements, maternal and fetal side effects, and patient acceptability. The mean SDI was shorter in the oxytocin group, but without statistical significance. Analgesic requirements and fetal side effects were similar in the two groups, but there was a higher incidence of nausea and vomiting in those patients receiving the maximum dose (1 mg hourly) of PGE2. On subjective assessment, clinicians considered oxytocin to be more effective (p less than 0.05), while midwives felt both regimes to be equally helpful. PGE2 oral tablets were significantly (p less than 0.05) more acceptable to the patients, who preferred the convenience of oral dosing, the absence of an i.v. line and the increased mobility. It is concluded that PGE2 tablets are a safe and effective method of stimulating labor following PROM, and highly acceptable to parturients. In those women in whom labor has not been established within 8 h of initiating PGE2 therapy, or in whom gastric side effects are troublesome, intravenous oxytocin should be substituted.", "A comparative study of labor induction has been performed on 471 consecutive patients. Primary amniotomy was performed in 227 cases, and 103 of these patients were stimulated, 57 patients with PGE2 tablets and 46 with oxytocin. In the remaining 124 cases labor was induced within 4 hours without medical stimulation. Primary amniotomy was omitted in 244 cases, as the head was not engaged and the cervix was unripe. After random allocation to the treatment groups 125 patients received PGE2 tablets (ProstinR), and 119 patients received oxytocin intravenously. After 2 days of stimulation without primary amniotomy, delivery was induced in 83 per cent of the patients receiving PGE2 and in 84 per cent of the patients receiving oxytocin. All patients on whom primary amniotomy had been performed were delivered on the first day. There was no difference in the success rate between PGE2 and oxytocin treatments in patients with the same Bishop score. The performance of amniotomy at the beginning of induction led to a significantly lower total dose as well as a lower maximal dose of PGE2 and oxytocin. There was no difference in the duration of active labor in patients receiving PGE2 or oxytocin. There were no differences in the incidence of fetal distress and low Apgar scores between the different groups. No serious side effects occurred. Vomiting and diarrhea in 14 patients (8 per cent) receiving PGE2 was in contrast to 3 patients with these symptoms (2 per cent) in the oxytocin group. Oral administration of PGE2 is a convenient, effective and safe alternative to oxytocin for the induction of labor; however, PGE2 was not found superior to oxytocin in cases with a low Bishop score.", "A comparative study of the efficacy of oral prostaglandin E2 and buccal tablets of demoxytocin for induction of labor in overdue pregnancies was made in groups of randomly selected patients. Labor was successfully induced in 95.7% of the women in the prostaglandin group and 92.1% of the women in the demoxytocin group. Although the operative delivery rate was low in both groups, it was significantly higher for the demoxytocin group. A low rate of perinatal distress was recorded and there were no serious side effects in either group. The time from start of induction until delivery, as well as the time from amniotomy until delivery, were compared for primiparae and multiparae separately. No significant differences were found. The blood loss during the third stage of labor was lower in the prostaglandin group. We find oral induction of labor in overdue pregnancies effective, safe and convenient." ]

[ "8596268", "10365192", "15223093", "16415698", "15039761", "15730349", "12757964" ]

[ "Haloperidol antagonism of cue-elicited cocaine craving.", "Pergolide mesylate for cocaine abuse: a controlled preliminary trial.", "A double-blind placebo-controlled pilot study of risperidone for decreasing cue-elicited craving in recently withdrawn cocaine dependent patients.", "The efficacy of olanzapine for decreasing cue-elicited craving in individuals with schizophrenia and cocaine dependence: a preliminary report.", "Agonist-like or antagonist-like treatment for cocaine dependence with methadone for heroin dependence: two double-blind randomized clinical trials.", "A placebo-controlled screening trial of olanzapine, valproate, and coenzyme Q10/L-carnitine for the treatment of cocaine dependence.", "A pilot trial of olanzapine for the treatment of cocaine dependence." ]

[ "Studies of cocaine-dependent subjects have shown that re-exposure to environmental cues previously associated with cocaine use produces a strong conditioned response characterised by autonomic hyperarousal and increases in subjective measures of cocaine craving.\n To evaluate the role of dopamine release by such cues, 20 cocaine-dependent inpatients were randomised in a single-dose, crossover, placebo-controlled design, to haloperidol (4 mg by mouth) and placebo. Plasma homovanillic acid (HVA, a dopamine metabolite), adrenocorticotropic hormone (ACTH), and cortisol were assayed before and after cue exposure. Craving and anxiety were measured before and after cues with visual analogue scales for desire to use cocaine now and for mood changes.\n Cocaine cues significantly increased anxiety, ACTH, cortisol, and HVA. Increases in anxiety and craving resulting from cue exposure were significantly antagonised by pretreatment with haloperidol.\n It has long been hypothesised that increases in extracellular concentrations of dopamine mediate the acute reinforcing effects of cocaine. Our data suggest that dopamine release may also mediate some of the conditioned responses to cocaine cues.", "A small, controlled study was conducted to assess whether pergolide mesylate has clinical promise as a treatment for cocaine abuse prior to embarking on a larger, randomized, double-blind, controlled trial. Fourteen individuals were placed on placebo for 2 weeks, followed by a 24-week single-blind study in which they were placed on pergolide for 12 weeks, followed by placebo for 12 weeks. Another 14 patients received single-blind placebo for two weeks and then were randomized into a 24-week double-blind, placebo-controlled, multiple baseline design. Initially, patients enrolled in the study were placed on risperidone (n = 9) or placebo (n = 5). During the first 12 weeks, retention was worse for those receiving pergolide compared to risperidone or placebo. Neither risperidone nor pergolide were more efficacious in reducing cocaine use than placebo. Although earlier open studies found pergolide to show promise as a treatment for cocaine abuse, this study did not support these earlier findings. Comparing an agent to both an active control and placebo group may better predict whether a promising new agent will have clinical utility compared to the standard open trial.", "Cocaine use causes an initial increase in dopamine and serotonin neurotransmission that is largely responsible for the pleasurable and reinforcing effects of the drug. Dysregulation of these neurotransmitters during withdrawal plays an important role in craving. Recent research has focused on the use of dopamine and serotonin antagonists early in recovery to reduce cocaine craving in both schizophrenic and non-schizophrenic cocaine dependent patients. This 2-week, double blind, placebo-controlled study compared risperidone vs. placebo in reducing cue-elicited cocaine craving. Thirty-four subjects with cocaine dependence were randomized to either risperidone or a placebo and underwent a weekly cue-exposure procedure. Although both groups had a reduction in craving over time, there were no significant differences among those treated with risperidone (n=19) compared to those taking a placebo (n=16) on the four craving dimensions. The results do not support the hypothesis that risperidone reduces cocaine craving among non-schizophrenic cocaine-dependent individuals.", "Although a growing body of research suggests that atypical neuroleptic medications are efficacious in the treatment of cocaine addiction among individuals with schizophrenia, more rigorously controlled trials are needed. To extend this research, we performed a 6-week double-blind study comparing olanzapine to haloperidol with the primary objective of reducing cue-elicited cocaine craving and the secondary aims of decreasing substance use, improving psychiatric symptoms, and determining an effect size for future studies.\n Thirty-one subjects with cocaine dependence and schizophrenia were randomized to olanzapine or haloperidol, underwent a cue-exposure procedure, and completed psychiatric and substance abuse ratings.\n Individuals in the olanzapine group who completed the study had a significant reduction on the energy subscale of the Voris Cocaine Craving Scale at study completion compared with individuals in the haloperidol group. The olanzapine-treated group also had lower, but not statistically significant, PANSS General Psychopathology Subscale scores and fewer positive urine toxicology screens compared with those in the haloperidol group.\n This small, but rigorously controlled, pilot trial provides additional evidence for the use of atypical antipsychotics for the treatment of individuals with co-occurring schizophrenia and cocaine dependence. Reductions in craving were associated with medium to large effect sizes.", "Concurrent abuse of cocaine and heroin is a common problem. Methadone is effective for opioid dependence. The question arises as to whether combining agonist-like or antagonist-like medication for cocaine with methadone for opioid dependence might be efficacious. Two parallel studies were conducted. One examined sustained release d-amphetamine and the other risperidone for cocaine dependence, each in combination with methadone. In total, 240 subjects (120/study) were recruited, who were both cocaine and heroin dependent and not currently receiving medication. All provided consent. Both studies were carried out for 26 weeks, randomized, double-blind and placebo controlled. Study I compared sustained release d-amphetamine (escalating 15-30 or 30-60 mg) and placebo. Study II examined risperidone (2 or 4 mg) and placebo. All subjects underwent methadone induction and were stabilized at 1.1 mg/kg. Subjects attended clinic twice/week, provided urine samples, obtained medication take-home doses for intervening days, and completed self-report measures. Each had one behavioral therapy session/week. In Study I, reduction in cocaine use was significant for the 30/60 mg dose compared to the 15/30 mg and placebo. Opioid use was reduced in all groups with a trend toward greater reduction in the 30/60 mg d-amphetamine group. In Study II, methadone reduced illicit opioid use but cocaine use did not change in the risperidone or placebo groups. There were no adverse medication interactions in either study. The results provide support for the agonist-like (d-amphetamine) model in cocaine dependence treatment but not for antagonist-like (risperidone) treatment. They coincide with our previous reports of amphetamine or risperidone administered singly in cocaine-dependent individuals.", "To conduct a medication screening trial on the efficacy of olanzapine, valproate or coenzyme Q10/L-carnitine combination versus placebo for the treatment of cocaine dependence.\n A four-arm, modified blinded, parallel group study in an out-patient setting using the Cocaine Rapid Efficacy and Safety Trials (CREST) study design.\n The study was performed at the New York Medications Development Research Unit (MDRU).\n All participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and provided at least two urine samples positive for benzoylecgonine (BE) during the 2-week screening period. Sixty-eight participants were enrolled with 39 completing the study.\n After a 2-week screening period, 68 subjects were assigned randomly to receive either olanzapine (10 mg/day), valproate (1500 mg/day), coenzyme Q10 (200 mg/day) and L-carnitine (500 mg/day) combination or placebo for an 8-week treatment period. All subjects also received individual cognitive behavioral counseling during treatment.\n Primary outcome measures included quantitative urine benzoylecgonine (BE) levels, self-report of drug use, and global impression scores. Secondary outcomes included cocaine craving, study retention and related psychosocial measures. Safety measures included adverse event monitoring, vital signs, and extrapyramidal side-effects tests.\n Study retention was similar across all treatment groups, and all groups showed improvement across most measures of treatment efficacy over the duration of the study. None of the study medications, however, were superior to placebo on any of the primary or secondary outcome measures. Cocaine use, as measured by urine BE levels and self-report, was not significantly lower than placebo in any of the drug treatment groups. All study medications were equally well tolerated, and few medication side effects were observed.\n This pilot study does not support the effectiveness of olanzapine, valproate or coenzyme Q10/L-carnitine combination for the treatment of cocaine dependence.", "Multiple lines of evidence suggest both dopaminergic and serotonergic involvement in the reinforcing effects of cocaine. Medications such as olanzapine, which block dopamine D2 receptors, as well as serotonin receptors 5HT2A and 5HT2C may be able to reduce cocaine use in cocaine dependent patients by reducing the euphoric effects of cocaine and attenuating cocaine craving.\n This was a 12-week, double blind, placebo controlled, pilot trial involving 30 cocaine dependent subjects. Subjects received either olanzapine (10 mg/day) or identical placebo. Outcome measures included treatment retention, qualitative urine benzoylecgonine tests, cocaine craving, clinical global impression scores, and results from the addiction severity index.\n Treatment retention was slightly, but significantly, better in the placebo-treated subjects. Placebo-treated subjects were more likely to be abstinent from cocaine during the trial compared to olanzapine-treated subjects, based on urine benzoylecgonine results. Olanzapine was not superior to placebo in any outcome measure.\n The results of this trial do not support the usefulness of olanzapine for the treatment of cocaine dependence. In fact, olanzapine may worsen cocaine treatment outcome." ]

[ "8588538", "17012004" ]

[ "Risk factors for leg ulcer recurrence: a randomized trial of two types of compression stocking.", "Prevention of recurrence of venous ulceration: randomized controlled trial of class 2 and class 3 elastic compression." ]

[ "Patients with recently healed leg ulceration were entered into a study of leg ulcer recurrence. In all, 188 patients [69% women, mean age = 72 (SD = 12) years] were entered into the study, of whom 166 were considered suitable for ready-made stockings and were randomized to one of two class II below-knee compression stockings and followed for at least 18 months. The remaining patients required either made-to-measure stockings (5) or could not tolerate stockings owing to friable skin and were treated by other methods (17). Overall cumulative recurrence rate was 26% after 1 year and 31% at 18 months. Independent risk factors for (RR = 2.34, p = 0.021) and unsuitability for stockings (RR = 2.52, p = 0.013). The randomized groups had similar stockings, 25 (15%) could not put their stockings on at all and 43 (26%) were only able to put them on with great difficulty. The two stocking types differed significantly in this regard when analysed for trend.", "To compare venous ulcer recurrence and compliance with two strengths of compression hosiery.\n This study was a randomized controlled trial with a 5-year follow-up. The setting was the leg ulcer clinics of a teaching and a district general hospital in Scotland, United Kingdom. Patients were 300 outpatients with recently healed venous ulcers, with no significant arterial disease, rheumatoid disease, or diabetes mellitus. Interventions were fitting and supply of class 2 or class 3 compression hosiery. Four-monthly refitting by trained orthotists and surveillance by specialist nurses were performed. The main outcome measures were recurrence of leg ulceration and compliance with treatment.\n Thirty-six percent (107/300) of patients had recurrent leg ulceration by 5 years. Recurrence occurred in 59 (39%) of 151 class 2 elastic compression cases and in 48 (32%) of class 3 compression cases. One hundred six patients did not comply with their randomized compression class, 63 (42%) in class 3 and 43 (28%) in class 2. The difference in recurrence is not statistically significant, but our estimate of the effectiveness of class 3 hosiery is diluted by the lower compliance rate in this group. Restricted ankle movement and four or more previous ulcers were associated with a higher risk of recurrence.\n There was no evidence of a difference in recurrence rates at the classic level of significance (5%), but the lowest recurrence rates were seen in people who wore the highest degree of compression. Therefore, patients should wear the highest level of compression that is comfortable." ]

[ "12240812", "1608408", "16954488", "10160376", "15770171", "17403764", "16737346", "11593835", "15282232", "12183309", "10478162", "15797158", "8737434", "9582043", "11418253", "6406886", "9892450", "12106622", "15198764", "12392122", "16708003", "11960538", "15866255", "9024439", "7887759", "8046193" ]

[ "Fetal health surveillance: a community-wide approach versus a tailored intervention for the implementation of clinical practice guidelines.", "A randomized trial of a program to reduce the use of psychoactive drugs in nursing homes.", "An educational intervention to improve physician reporting of adverse drug reactions: a cluster-randomized controlled trial.", "The impact of face-to-face educational outreach on diarrhoea treatment in pharmacies.", "Implementation of the Dutch low back pain guideline for general practitioners: a cluster randomized controlled trial.", "Barriers to optimal antibiotic use for community-acquired pneumonia at hospitals: a qualitative study.", "Rational prescribing in primary care (RaPP): a cluster randomized trial of a tailored intervention.", "Randomised controlled trial of tailored strategies to implement guidelines for the management of patients with depression in general practice.", "Optimizing antibiotic prescribing for acute cough in general practice: a cluster-randomized controlled trial.", "Cluster randomised controlled trial of tailored interventions to improve the management of urinary tract infections in women and sore throat.", "Confidential prescriber feedback and education to improve antibiotic use in primary care: a controlled trial.", "A short educational intervention on communication skills improves the quality of screening for Chlamydia in GPs in Belgium: a cluster randomised controlled trial.", "Small group intervention vs formal seminar for improving appropriate drug use.", "Effect of local medical opinion leaders on quality of care for acute myocardial infarction: a randomized controlled trial.", "A clinical trial of tailored office systems for preventive service delivery. The Study to Enhance Prevention by Understanding Practice (STEP-UP).", "Improving drug-therapy decisions through educational outreach. A randomized controlled trial of academically based \"detailing\".", "Methods to encourage the use of antenatal corticosteroid therapy for fetal maturation: a randomized controlled trial.", "Improving the quality of anticoagulation of patients with atrial fibrillation in managed care organizations: results of the managing anticoagulation services trial.", "A randomised controlled trial of a tailored multifaceted strategy to promote implementation of a clinical guideline on induced abortion care.", "Secondary prevention of cardiovascular disease: a randomised trial of training in information management, evidence-based medicine, both or neither: the PIER trial.", "Cluster randomized controlled trial of the effectiveness of audit and feedback and educational outreach on improving nursing practice and patient outcomes.", "Improving the quality of hemodialysis treatment: a community-based randomized controlled trial to overcome patient-specific barriers.", "Group versus individual academic detailing to improve the use of antihypertensive medications in primary care: a cluster-randomized controlled trial.", "Improving care for minority children with asthma: professional education in public health clinics.", "Enhancing physician adoption of practice guidelines. Dissemination of influenza vaccination guideline using a small-group consensus process.", "Improving treatment of late life depression in primary care: a randomized clinical trial." ]

[ "The decreased use of electronic fetal monitoring (EFM) for healthy women in labour and the increased provision of professional support to all women in labour is recommended by experts. We evaluated the effectiveness of a community-wide approach to transferring research results to practice using a regional committee, newsletter articles and annual conference presentations compared with an additional tailored hospital intervention involving workshops to enhance self-efficacy for nurses, policy review, multidisciplinary meetings, rounds and unit discussions.\n We compared the proportion of women at low risk who received EFM and the proportion of nurses' time spent providing labour support before and after the intervention within each of 4 hospitals (2 tertiary and 2 secondary). One hospital of either type was randomly selected to receive the tailored intervention. Randomly selected charts (n = 200) were reviewed for the use of EFM at each hospital before (1995) and after (1996) the intervention. Trained observers at randomly selected times recorded the nurses' activities, including time spent providing labour support before and after the intervention.\n At the intervention secondary hospital, there was a large decrease in the use of EFM, from 90.1% before to 41.0% after the intervention (p < 0.001), but no change in nurses' time spent providing labour support. At the intervention tertiary hospital there was no change in EFM rates, but there was a small, statistically significant increase in time spent providing labour support (23.5% to 29.8%, p < 0.001). A negative effect on time spent providing labour support was found at the control secondary hospital (decrease from 19.6% to 12.8%, p < 0.001), with no change in the EFM rate. At the control tertiary hospital there was a small decrease in the use of EFM, from 99.5% to 91.4% (p < 0.001), but no change in time spent providing labour support.\n The results are mixed, and the tailored intervention thus appeared to have limited effects. No association was found between the reduction in the use of EFM and an increase in nurses' time spent providing labour support.", "Although psychoactive medications have substantial side effects in the elderly, these drugs are used frequently in nursing homes. Few interventions have succeeded in changing this situation, and little is known about the clinical effects of such interventions.\n We studied six matched pairs of nursing homes; at one randomly selected nursing home in each pair, physicians, nurses, and aides participated in an educational program in geriatric psychopharmacology. At base line we determined the type and quantity of drugs received by all residents (n = 823), and a blinded observer performed standardized clinical assessments of the residents who were taking psychoactive medications. After the five-month program, drug use and patient status were reassessed.\n Scores on an index of psychoactive-drug use, measuring both the magnitude and the probable inappropriateness of medication use, declined significantly more in the nursing homes in which the program was carried out (experimental nursing homes) than in the control nursing homes (decrease, 27 percent vs. 8 percent; P = 0.02). The use of antipsychotic drugs was discontinued in more residents in the experimental nursing homes than in the control nursing homes (32 percent vs. 14 percent); the comparable figures for the discontinuation of long-acting benzodiazepines were 20 percent vs. 9 percent, and for antihistamine hypnotics, 45 percent vs. 21 percent. In the experimental nursing homes residents who were initially taking antipsychotic drugs showed less deterioration on several measures of cognitive function than similar residents in the control facilities, but they were more likely to report depression. Those who were initially taking benzodiazepines or antihistamine hypnotic agents reported less anxiety than controls but had more loss of memory. Most other measures of clinical status remained unchanged in both groups.\n An educational program targeted to physicians, nurses, and aides can reduce the use of psychoactive drugs in nursing homes without adversely affecting the overall behavior and level of functioning of the residents.", "Data on the adverse effects of newly marketed drugs are limited. Voluntary reporting is an important part of postmarketing surveillance but is underused by physicians.\n To evaluate the effectiveness of educational outreach visits for improving adverse drug reaction (ADR) reporting by physicians.\n A cluster-randomized controlled trial covering all National Health System physicians in the north of Portugal, with intervention in March 2004 through July 2004, and 13 to 16 months of follow-up. A total of 1388 physicians were assigned in 4 spatial clusters to the intervention group, and 5063 were assigned in 11 clusters to the control group.\n One-hour educational outreach visits tailored to training needs identified in a previous study.\n Change in total number of reported ADRs and number of serious, high-causality, unexpected, and new-drug-related ADRs, using generalized linear mixed models adjusted for baseline ADR reporting, age, specialty, and work setting.\n At baseline, ADR reporting rates (per 1000 physician-years) did not differ significantly between the intervention groups and the control groups in reporting ADRs overall (7.6 vs 11.3), nor did they differ significantly by category: serious, 4.3 vs 6.0; high-causality, 5.4 vs 7.6; unexpected, 1.6 vs 3.5; and new-drug-related ADRs, 3.7 vs 3.8. (P>.05 for all comparisons). The control group had no significant increase in ADR reports during follow-up. The adjusted increase in ADR reporting rates attributable to intervention was 90.19 for total ADRs (95% confidence interval [CI], 54.51-125.87; relative risk [RR], 10.23; 95% CI, 3.81-27.51), 30.16 for serious ADRs (95% CI, 18.84-41.47; RR, 6.32; 95% CI, 2.09-19.16), 64.90 for high-causality ADRs (95% CI, 38.38-91.42; RR, 8.75; 95% CI, 3.05-25.07), 28.04 for unexpected ADRs (95% CI, 16.25-39.83; RR, 30.21; 95% CI, 4.54-200.84), and 42.17 for new-drug-related ADRs (95% CI, 21.58-62.76; RR, 8.05; 95% CI, 2.10 -30.83). The greatest difference occurred during the first 4 months after intervention, but differences remained statistically significant for 12 months.\n A targeted outreach program may improve high-quality reporting of ADRs among physicians.", "Private pharmacies are an important source of health care in developing countries. A number of studies have documented deficiencies in treatment, but little has been done to improve practices. We conducted two controlled trials to determine the efficacy of face-to-face educational outreach in improving communication and product sales for cases of diarrhoea in children in 194 private pharmacies in two developing countries. A training guide was developed to enable a national diarrhoea control programme to identify problems and their causes in pharmacies, using quantitative and qualitative research methods. The guide also facilitates the design, implementation, and evaluation of an educational intervention, which includes brief one-on-one meetings between diarrhoea programme educators and pharmacists/owners, followed by one small group training session with all counter attendants working in the pharmacies. We evaluated the short-term impact of this intervention using a before-and-after comparison group design in Kenya, and a randomized controlled design in Indonesia, with the pharmacy as unit of analysis in both countries (n = 107 pharmacies in Kenya; n = 87 in Indonesia). Using trained surrogate patients posing as mothers of a child under five with diarrhoea, we measured sales of oral rehydration salts (ORS); sales of antidiarrhoeal agents; and history-taking and advice to continue fluids and food. We also measured knowledge about dehydration and drugs to treat diarrhoea among Kenyan pharmacy employees after training. Major discrepancies were found at baseline between reported and observed behaviour. For example, 66% of pharmacy attendants in Kenya, and 53% in Indonesia, reported selling ORS for the previous case of child diarrhoea, but in only 33% and 5% of surrogate patient visits was ORS actually sold for such cases. After training, there was a significant increase in knowledge about diarrhoea and its treatment among counter attendants in Kenya, where these changes were measured. Sales of ORS in intervention pharmacies increased by an average of 30% in Kenya (almost a two-fold increase) and 21% in Indonesia compared to controls (p < 0.05); antidiarrhoeal sales declined by an average of 15% in Kenya and 20% in Indonesia compared to controls (p < 0.05). There was a trend toward increased communication in both countries, and in Kenya we observed significant increases in discussion of dehydration during pharmacy visits (p < 0.05). We conclude that face-to-face training of pharmacy attendants which targets deficits in knowledge and specific problem behaviours can result in significant short-term improvements in product sales and communication with customers. The positive effects and cost-effectiveness of such programmes need to be tested over a longer period for other health problems and in other countries.", "Cluster randomized controlled trial for a multifaceted implementation strategy.\n To assess the effectiveness of tailored interventions (multifaceted implementation strategy) to implement the Dutch low back pain guideline for general practitioners with regard to adherence to guideline recommendations.\n Guidelines for the management of low back pain in primary care have been developed in various countries, but little is known about the optimal implementation strategy. A multifaceted implementation strategy was developed to overcome identified barriers to the implementation of the Dutch low back pain guideline for general practitioners.\n General practitioners were randomized to an intervention or a control group. The general practitioners in the intervention group (n = 21) received tailored interventions consisting of the Dutch low back pain guideline for general practitioners, a 2-hour educational and clinical practice workshop; two scientific articles on low back pain management; the guideline for occupational physicians; a tool for patient education; and a tool for reaching agreement on low back care with physical, exercise, and manual therapists. The control group (n = 20) received no intervention. The participating general practitioners were asked to recruit consecutive patients with a new episode of low back pain as the main reason for consultation. General practitioners completed registration forms of each individual consultation with regard to the main outcome measures: advice and information, referral to other health-care providers, and prescription of medication.\n Forty-one of the 67 randomized general practitioners reported on a total of 616 consultations for 531 patients with nonspecific low back pain. The advice and explanation provided by the general practitioners, the prescription of paracetamol or nonsteroidal anti-inflammatory drugs, and prescription of pain medication on atime contingent or a pain contingent basis showed no statistically significant differences between the intervention and control groups. There were also no differences in overall referral rate. However, in follow-up consultations fewer patients were referred to a physical or exercise therapist by the general practitioners in the intervention group than in the control group.\n The multifaceted intervention strategy modestly improved implementation (for parts of the recommendations in) the Dutch low back pain guideline by general practitioners and produced small concomitant changes in patient management. The implementation strategy produced fewer referrals to therapists during follow-up consultations.", "Physician adherence to key recommendations of guidelines for community-acquired pneumonia (CAP) is often not optimal. A better understanding of factors influencing optimal performance is needed to plan effective change.\n The authors used semistructured interviews with care providers in three Dutch medium-sized hospitals to qualitatively study and understand barriers to appropriate antibiotic use in patients with CAP. They discussed recommendations about the prescription of empirical antibiotic therapy that adheres to the guidelines, timely administration of antibiotics, adjusting antibiotic dosage to accommodate decreased renal function, switching and streamlining therapy, and blood and sputum culturing. The authors then classified the barriers each recommendation faced into categories using a conceptual framework (Cabana).\n Eighteen interviews were performed with residents and specialists in pulmonology and internal medicine, with medical microbiologists and a clinical pharmacist. Two additional multidisciplinary small group interviews which included nurses were performed. Each guideline recommendation elicited a different type of barrier. Regarding the choice of guideline-adherent empirical therapy, treating physicians said that they worried about patient outcome when prescribing narrow-spectrum antibiotic therapy. Regarding the timeliness of antibiotic administration, barriers such as conflicting guidelines and organisational factors (for example, delayed laboratory results, antibiotics not directly available, lack of time) were reported. Not streamlining therapy after culture results became available was thought to be due to the physicians' attitude of \"never change a winning team\".\n Efforts to improve the use of antibiotics for patients with CAP should consider the range of barriers that care providers face. Each recommendation meets its own barriers. Interventions to improve adherence should be tailored to these factors.", "A gap exists between evidence and practice regarding the management of cardiovascular risk factors. This gap could be narrowed if systematically developed clinical practice guidelines were effectively implemented in clinical practice. We evaluated the effects of a tailored intervention to support the implementation of systematically developed guidelines for the use of antihypertensive and cholesterol-lowering drugs for the primary prevention of cardiovascular disease.\n We conducted a cluster-randomized trial comparing a tailored intervention to passive dissemination of guidelines in 146 general practices in two geographical areas in Norway. Each practice was randomized to either the tailored intervention (70 practices; 257 physicians) or control group (69 practices; 244 physicians). Patients started on medication for hypertension or hypercholesterolemia during the study period and all patients already on treatment that consulted their physician during the trial were included. A multifaceted intervention was tailored to address identified barriers to change. Key components were an educational outreach visit with audit and feedback, and computerized reminders linked to the medical record system. Pharmacists conducted the visits. Outcomes were measured for all eligible patients seen in the participating practices during 1 y before and after the intervention. The main outcomes were the proportions of (1) first-time prescriptions for hypertension where thiazides were prescribed, (2) patients assessed for cardiovascular risk before prescribing antihypertensive or cholesterol-lowering drugs, and (3) patients treated for hypertension or hypercholesterolemia for 3 mo or more who had achieved recommended treatment goals. The intervention led to an increase in adherence to guideline recommendations on choice of antihypertensive drug. Thiazides were prescribed to 17% of patients in the intervention group versus 11% in the control group (relative risk 1.94; 95% confidence interval 1.49-2.49, adjusted for baseline differences and clustering effect). Little or no differences were found for risk assessment prior to prescribing and for achievement of treatment goals.\n Our tailored intervention had a significant impact on prescribing of antihypertensive drugs, but was ineffective in improving the quality of other aspects of managing hypertension and hypercholesterolemia in primary care.", "Various methods are available for implementing change in the clinical behaviour of general practitioners (GPs). Although passive dissemination of information is generally ineffective, other methods can be variably effective. Few studies have investigated the impact of tailored methods.\n To determine whether methods tailored to overcome obstacles to change using psychological theories are more effective than dissemination alone in the implementation of guidelines for depression among GPs.\n Randomised controlled trial.\n Sixty general practices in England; 30 GPs in the control group, 34 in the intervention group.\n Practitioners identified patients presenting with depression before and after the implementation of guidelines (control group n = 192 in the first data collection, n = 181 in the second; intervention group n = 210 in the first data collection and n = 197 in the second). The main outcome measures were: record of adherence to guideline recommendations in clinical records; proportion of patients with Beck Depression Inventory (BDI) score less than 11 at 16 weeks after diagnosis.\n In comparison with the control group, in the group of GPs receiving tailored implementation, there were increases in the proportions of patients assessed for suicide risk. In the intervention group, the proportion of patients with BDI scores of less than 11 at 16 weeks increased.\n Obstacles to implementation can be identified and strategies tailored to address them. The findings indicate a new approach for research to understand and develop methods of implementation.", "To assess the effect of a tailored professional intervention, including academic detailing, on antibiotic prescribing for acute cough.\n In a cluster-randomized controlled before and after study 85 Flemish GPs included adult patients with acute cough consulting in the periods February-April 2000 and 2001. The intervention consisted of a clinical practice guideline for acute cough, an educational outreach visit and a postal reminder to support its implementation in January 2001. Antibiotic prescribing rates and patients' symptom resolution were the main outcome measures.\n Thirty-six of 42 GPs received the intervention and 35 of 43 GPs served as controls; 1503 patients were eligible for analysis. Only in the intervention group were patients less likely to receive antibiotics after the intervention [OR(adj) (95% CI)=0.56 (0.36-0.87)]. Prescribed antibiotics were also more in line with the guideline in the intervention group [1.90 (0.96-3.75)] and less expensive from the perspective of the National Sickness and Invalidity Insurance Institute [MD(adj) (95% CI)= Euro -6.89 [-11.77-(-2.02)]]. No significant differences were found between the groups for the time to symptom resolution.\n An (inter)actively delivered tailored intervention implementing a guideline for acute cough is successful in optimizing antibiotic prescribing without affecting patients' symptom resolution. Further research efforts should be devoted to cost-effectiveness studies of such interventions.", "To assess the effectiveness of tailored interventions to implement guidelines for urinary tract infections in women and sore throat.\n Unblinded, cluster randomised pretest-post-test trial.\n 142 general practices in Norway.\n 72 practices received interventions to implement guidelines for urinary tract infection and 70 practices received interventions to implement guidelines for sore throat, serving as controls for each other. 59 practices in the urinary tract infection group and 61 practices in the sore throat group completed the study. Outcomes were measured in 16 939 consultations for sore throat and 9887 consultations for urinary tract infection.\n Interventions were developed to overcome identified barriers to implementing the guidelines. The main components of the tailored interventions were patient educational material, computer based decision support and reminders, an increase in the fee for telephone consultations, and interactive courses for general practitioners and practice assistants.\n Changes in rates of use of antibiotics, laboratory tests, and telephone consultations. Results: Patients in the sore throat group were 3% less likely to receive antibiotics after the intervention. Women with symptoms of urinary tract infection in the intervention group were 5.1% less likely to have a laboratory test ordered. No significant differences were found between the groups for the other outcomes. Large variation was found across the included practices in the rates of antibiotic prescription, use of laboratory tests and telephone consultations, and in the extent of change for all three outcome measures.\n Passively delivered, complex interventions targeted at identified barriers to change had little effect in changing practice.", "Antibiotics are a medication class for which inappropriate prescribing is frequently described. We sought to assess the effectiveness of a mailed intervention combining confidential prescribing feedback with targeted educational bulletins in increasing the use of less expensive, first-line antibiotics by practising physicians.\n The participants were 251 randomly selected primary care physicians from southern Ontario who consented to participate (135 in the feedback group and 116 in the control group). Prescribing data were obtained from the claims database of the Ontario Drug Benefit program, which covers all Ontarians over age 65 years for drugs selected from a minimally restrictive formulary. Confidentially prepared profiles of antibiotic prescriptions coupled with guidelines-based educational bulletins were mailed to the intervention group every 2 months for 6 months. The control group received no intervention until after completion of the study. The main outcome measures were change from baseline in physician's median antibiotic cost and proportion of episodes of care in which a prespecified first-line antibiotic was used first.\n The median prescription cost of about $11 remained constant in the feedback group but rose in the control group (change of $0.05 v. $3.37, p < 0.002). First-line drug use increased in the feedback group but decreased in the control group (change of 2.6% v. -1.7%, p < 0.01). In a mailed survey of 100 feedback recipients (response rate 76%), 82% indicated that they would participate readily in another, similar program.\n A simple program of confidential feedback and educational materials blunted cost increases, increased the use of first-line antibiotics and was highly acceptable to Ontario primary care physicians.", "An accurate algorithm for screening for chlamydial infections is available in general practice, but GPs experience numerous barriers to sexually transmitted infections (STI) counselling. In this study we assessed if a short educational package, under the form of a commented video footage on communication skills, was helpful in implementing the screening strategy. A cluster randomised controlled trial was carried out in 36 general practitioners in Antwerp, Belgium. Main outcome measures were: number of patients included in the risk assessment, number of patients tested, and proportion of appropriately tested patients. The results show that GPs in the intervention group did not include more patients overall, but that the quality of the screening process was significantly better (81.6% versus 56.2% appropriate tests, P = 0.02). Conclusively, GPs who participated in a short educational package on communication skills, selected eligible candidates for screening more accurately and decreased the risk of overscreening.", "In an attempt to evaluate the efficacy of different methods of interventions to improve the appropriate use of drugs for acute diarrhoea, a controlled study has been carried out in 6 districts in Yogyakarta and Central Java provinces, Indonesia. This study was designed to investigate the impacts of two different methods of educational intervention, i.e. a small group face-to-face intervention and a formal seminar for prescribers, on prescribing practice in acute diarrhoea. The districts were randomly assigned into 3 groups and 15 health centers were selected from each district. Prescribers in Group 1 underwent a small group face-to-face intervention conducted in the respective health center. Those in Group 2 attended a formal seminar conducted at the district level. Prescribers in Group 3 served as the control group. Both interventions were given on a single occasion without follow-up supervision or monitoring. Written information materials on the appropriate management of acute diarrhoea were developed and were provided to all prescribers in the intervention groups. Focus group discussions (FGDs) involving prescribers and consumers in the 6 districts were carried out to identify various underlying motivations of drug use in acute diarrhoea. The findings of the FGDs were used as part of the intervention materials. To evaluate the impacts of these interventions on prescribing practice, a prescribing survey for patients under five years old with acute diarrhoea was carried out in health centers covering 3-month periods before and after the intervention. The results showed that both interventions were equally effective in improving the levels of knowledge of prescribers about the appropriate management of acute diarrhoea. They were also partially effective in improving the appropriate use of drugs, reducing the use of non-rehydration medications. There was a highly significant reduction of antimicrobial usage either after small-group face-to-face intervention (77.4 +/- 2.7% to 60.4 +/- 2.9%; P < 0.001) or formal seminar (82.3 +/- 3.0% to 72.3 +/- 3.6%; P < 0.001), and the former caused significantly (P < 0.001) greater reduction than the latter. There was also a significant (P < 0.01) reduction in the usage of antidiarrhoeals after both interventions, i.e. from 20.3 +/- 3.7% to 12.5 +/- 3.3% (P < 0.01) after face-to-face intervention and from 48.5 +/- 4.1% to 27.0 +/- 4.3% (P < 0.01) after seminar. However, the formal seminar had a significantly (P < 0.01) greater impact than the small group face-to-face intervention. There was also a trend toward increased oral rehydration solution (ORS) usage after both interventions, but this did not achieve the level of statistical significance (P > 0.05). No changes were observed in the control group. Although the small group face-to-face intervention did not appear to offer greater impacts over large seminars in improving the appropriate use of drugs in acute diarrhoea, since the unit cost of training is far less costly than the seminar, it might be feasibly implemented in the existing supervisory structure of the health system.", "The effectiveness of recruiting local medical opinion leaders to improve quality of care is poorly understood.\n To evaluate a guideline-implementation intervention of clinician education by local opinion leaders and performance feedback to (1) increase use of lifesaving drugs (aspirin and thrombolytics in eligible elderly patients, beta-blockers in all eligible patients) for acute myocardial infarction (AMI), and (2) decrease use of a potentially harmful therapy (prophylactic lidocaine).\n Randomized controlled trial with hospital as the unit of randomization, intervention, and analysis.\n Thirty-seven community hospitals in Minnesota.\n All patients with AMI admitted to study hospitals over 10 months before (1992-1993, N=2409) or after (1995-1996, N=2938) the intervention.\n Using a validated survey, we identified opinion leaders at 20 experimental hospitals who influenced peers through small and large group discussions, informal consultations, and revisions of protocols and clinical pathways. They focused on (1) evidence (drug efficacy), (2) comparative performance, and (3) barriers to change. Control hospitals received mailed performance feedback.\n Hospital-specific changes before and after the intervention in the proportion of eligible patients receiving each study drug.\n Among experimental hospitals, the median change in the proportion of eligible elderly patients receiving aspirin was +0.13 (17% increase from 0.77 at baseline), compared with a change of -0.03 at control hospitals (P=.04). For beta-blockers, the respective changes were +0.31 (63% increase from 0.49 at baseline) vs +0.18 (30% increase from baseline) for controls (P=.02). Lidocaine use declined by about 50% in both groups. The intervention did not increase thrombolysis in the elderly (from 0.73 at baseline), but nearly two thirds of eligible nonrecipients were older than 85 years, had severe comorbidities, or presented after at least 6 hours.\n Working with opinion leaders and providing performance feedback can accelerate adoption of some beneficial AMI therapies (eg, aspirin, beta-blockers). Secular changes in knowledge and hospital protocols may extinguish outdated practices (eg, prophylactic lidocaine). However, it is more difficult to increase use of effective but riskier treatments (eg, thrombolysis) for frail elderly patients.", "The potential of primary care practice settings to prevent disease and morbidity through health habit counseling, screening for asymptomatic disease, and immunizations has been incompletely met. This study was designed to test a practice-tailored approach to increasing preventive service delivery with particular emphasis on health habit counseling.\n Group randomized clinical trial and multimethod process assessment.\n Seventy-seven community family practices in northeast Ohio.\n After a 1-day practice assessment, a nurse facilitator met with practice clinicians and staff and assisted them with choosing and implementing individualized tools and approaches aimed at increasing preventive service delivery.\n Summary scores of the health habit counseling, screening and immunization services recommended by the U.S. Preventive Services Task Force up to date for consecutive patients during randomly selected chart review days.\n A significant increase (p=0.015) in global preventive service delivery rates at the 1-year follow-up was found in the intervention group (31% to 42%) compared to the control group (35% to 37%). Rates specifically for health habit counseling (p=0.007) and screening services (p=0.048) were increased, but not for immunizations.\n An approach to increasing preventive service delivery that is individualized to meet particular practice needs can increase global preventive service delivery rates.", "Improving precision and economy in the prescribing of drugs is a goal whose importance has increased with the proliferation of new and potent agents and with growing economic pressures to contain health-care costs. We implemented an office-based physician education program to reduce the excessive use of three drug groups: cerebral and peripheral vasodilators, an oral cephalosporin, and propoxyphene. A four-state sample of 435 prescribers of these drugs was identified through Medicaid records and randomly assigned to one of three groups. Physicians who were offered personal educational visits by clinical pharmacists along with a series of mailed \"unadvertisements\" reduced their prescribing of the target drugs by 14 per cent as compared with controls (P = 0.0001). A comparable reduction in the number of dollars reimbursed for these drugs was also seen between the two groups, resulting in substantial cost savings. No such change was seen in physicians who received mailed print materials only. The effect persisted for at least nine months after the start of the intervention, and no significant increase in the use of expensive substitute drugs was found. Academically based \"detailing\" may represent a useful and cost-effective way to improve the quality of drug-therapy decisions and reduce unnecessary expenditures.", "Antenatal corticosteroids for fetal maturation have been underused, despite evidence for their benefits in cases of preterm birth.\n To evaluate dissemination strategies aimed at increasing appropriate use of this therapy.\n Twenty-seven tertiary care institutions were randomly assigned to either usual dissemination of practice recommendations (n = 14) or usual dissemination plus an active, focused dissemination effort (n = 13).\n Obstetricians and their preterm delivery cases at participating hospitals.\n Recommendations by a National Institutes of Health (NIH) Consensus Conference held in late February-early March 1994 were disseminated in early May 1994. Usual dissemination was publication of the recommendations and endorsement by the American College of Obstetricians and Gynecologists. Active dissemination was a year-long educational effort led by an influential physician and a nurse coordinator at each facility, consisting of grand rounds, a chart reminder system, group discussion of case scenarios, monitoring, and feedback.\n Use or nonuse of antenatal corticosteroids was abstracted from medical records of eligible women delivering at the participating hospitals in the 12 months immediately prior to release of the NIH recommendations (average number of records abstracted, 130) and in the 12 months following their release (average number of records abstracted, 122).\n Active dissemination significantly increased the odds of corticosteroid use after the conference. Use increased from 33.0% of eligible patients receiving corticosteroids to 57.6%, or by 75% over baseline, in usual dissemination hospitals. Use increased from 32.9% to 68.3%, oran 108% increase, in active dissemination hospitals. Gestational age and maternal diagnosis affected use of the therapy in complex ways.\n An active, focused dissemination effort increased the effectiveness of usual dissemination methods when combined with key principles to change physician practices.", "Randomized trials have indicated that well-managed anticoagulation with warfarin could prevent more than half of the strokes related to atrial fibrillation. However, many patients with atrial fibrillation who are eligible for this therapy either do not receive it or are not maintained within an optimal prothrombin time-international normalized ratio (INR) range. We sought to determine whether an anticoagulation service within a managed care organization would be a feasible alternative for providing anticoagulation care. We performed a multi-site randomized trial in six large managed care organizations in the United States. Subjects were aged 65 years or older and had nonvalvular atrial fibrillation. At each site, physician practices were divided into two geographically defined practice clusters; each site was randomly assigned to have one intervention and one control cluster. The intervention cluster received an anticoagulation service that satisfied specifications for high-quality anticoagulation care and was coordinated through the managed care organization. Control clusters continued with their usual provider-based care. We measured the proportion of time that warfarin-treated patients in each of the clusters (intervention and control) were in the target range for the INR at baseline, and again during a follow-up period. Five of the six selected sites succeeded at developing an anticoagulation service. Patients in the intervention and control clusters had similar demographic characteristics, contraindications to warfarin, and risk factors for stroke. Among patients (n = 144 in the intervention clusters; n = 118 in the control clusters) for whom data were available during the baseline and follow-up periods, the changes in percentages of time in the target range were similar for those in the intervention clusters (baseline: 47.7%; follow-up: 55.6%) and in the control clusters (baseline: 49.1%; follow-up: 52.3%; intervention effect: 5%; 95% confidence interval: -5% to 14%; P = 0.32). Although it was feasible in a managed care organization to implement anticoagulation services that were tailored to local circumstances, provision of this service did not improve anticoagulation care compared with usual care. The effect of the anticoagulation service was limited by the utilization of the service, the degree to which the referring physician supports strict adherence to recommended target ranges for the INR, and the ability of the anticoagulation service to identify and to respond to out-of-range values promptly.", "To evaluate the effectiveness and efficiency of a tailored multifaceted strategy, delivered by a national clinical effectiveness programme, to implement a guideline on induced abortion.\n Cluster randomised controlled trial.\n All 26 hospital gynaecology units in Scotland providing induced abortion care.\n Following the identification of barriers to guideline implementation, intervention units received a package comprising audit and feedback, unit educational meetings, dissemination of structured case records and promotion of a patient information booklet. Control units received printed guideline summaries alone.\n Compliance with five key guideline recommendations (primary outcomes) and compliance with other recommendations, patient satisfaction and costs of the implementation strategy (secondary outcomes).\n No effect was observed for any key recommendation: appointment with a gynaecologist within five days of referral (odds ratio 0.89; 95% confidence interval 0.50 to 1.58); ascertainment of cervical cytology history (0.93; 0.36 to 2.40); antibiotic prophylaxis or screening for lower genital tract infection (1.70; 0.71 to 5.99); use of misoprostol as an alternative to gemeprost (1.00; 0.27 to 1.77); and offer of contraceptive supplies at discharge (1.11; 0.48 to 2.53). Median pre-intervention compliance was near optimal for antibiotic prophylaxis and misoprostol use. No intervention benefit was observed for any secondary outcome. The intervention costs an average of pound 2607 per gynaecology unit.\n The tailored multifaceted strategy was ineffective. This was possibly attributable to high pre-intervention compliance and the limited impact of the strategy on factors outside the perceived control of clinical staff.", "Sub-optimal management of cardiovascular disease (CVD) patients is widespread in primary and secondary care, with risk factors frequently unrecorded or untreated.\n To investigate the effectiveness of educational interventions developed in primary care, on recording, prescribing and control of risk factors among all patients recorded by their general practitioner as having CVD.\n Factorial, duster-randomised controlled trial.\n Primary care teams representing the range of practice development in a geographically defined area in inner London.\n Participating practices were randomly allocated to one of the four intervention groups: information, evidence, both or neither. Interventions were tailored to suit individual practice needs. At a mean of 19 months after baseline, and three months after the end of intervention, practices carried out the follow-up assessment of recording, treatment, and control of risk factors in the same CVD patients.\n Adequate recording of all three risk factors, found inapproximately a third of patients at baseline, increased non-significantly by 10.5% (95% confidence interval [CI] = 3.9 to 24.9) in the information (versus not information) group and by 6.6% (95% [CI] = 8.9 to 22.0) in the evidence (versus not evidence) group. Factorial improvements in prescribing and control of risk factors tended not to be significant. Adequate recording of an three risk factors showed the greatest improvement in the information plus evidence group (19.9% increase, P for heterogeneity across the four groups < or = 0.001). Mean change from baseline to follow-up within the four intervention groups suggested improvements in the combined information plus evidence group in cholesterol recording (22.5% increase), prescribing of lipid lowering drugs (4.4% increase) and mean cholesterol (0.7 mmol/l decrease).\n Adequate risk factor recording did not differ between the information (versus not information) or the evidence (versus not evidence) intervention groups. Combined training in information systems and evidence-based medicine should be considered in the design of future interventions, to improve secondary prevention of CVD.", "Current understanding of implementation methods is limited, and research has focused on changing doctors' behaviors.\n Our aim was to evaluate the impact of audit and feedback and educational outreach in improving nursing practice and patient outcomes.\n Using a factorial design, cluster randomized controlled trial, we evaluated 194 community nurses in 157 family practices and 1078 patients with diagnosis of urinary incontinence (UI) for nurses compliance with evidence-linked review criteria for the assessment and management of UI and impact on psychologic and social well-being and symptoms. In the outreach arms, nurses' self-reported barriers informed development of tailored strategies.\n In comparison with educational materials alone, the implementation methods tested did not improve care at 6 months follow-up. Moderate rates of improvement (10-17% of patients) in performance for the assessment of UI and greater rates of improvement (20-30% of patients) for the management of care were found but effects were similar across arms. Improvement in patient outcomes was more consistently positive for educational outreach than for audit and feedback but differences were not significant. Adjustment for caseload size, severity or duration of UI and patients' age did not alter results.\n Printed educational materials alone may be as effective as audit and feedback and educational outreach in improving nurses' performance and outcomes of care for people with UI. Greater understanding of the underlying processes in improving performance within multidisciplinary teams through further, theory-driven studies with \"no intervention\" control groups and longer follow-up are needed.", "Mortality rates among US hemodialysis patients are the highest in the industrialized world at 23% per year. Measures of dialysis dose (Kt/V) correspond strongly with survival and are inadequate in one sixth of patients. Inadequate dialysis is also associated with increased hospitalizations and high inpatient costs. Our previous work identified 3 barriers to adequate hemodialysis: dialysis underprescription, catheter use, and shortened treatment time.\n To determine the effect of a tailored intervention on adequacy of hemodialysis.\n Community-based randomized controlled trial with recruitment from April 1999 to June 2000 at 29 hemodialysis facilities in northeast Ohio.\n Forty-four nephrologists and their 169 randomly selected adult patients receiving inadequate hemodialysis.\n Nephrologists were randomly assigned to an intervention (n = 21) or control (n = 23) group. For patients in the intervention group (n = 85), depending on the barrier(s) present, a study coordinator gave nephrologists recommendations about optimizing dialysis prescriptions, expedited conversion of catheters to surgically created grafts or fistulas, and educated patients about the importance of compliance with treatment time. Patients in the control group (n = 84) continued to receive usual care.\n Changes in Kt/V and specific barriers after 6 months.\n At baseline, intervention and control patients had similar Kt/V measurements, specific barriers, and demographic and medical characteristics. After 6 months, intervention patients had 2-fold larger increases in Kt/V compared with control patients (+0.20 vs +0.10; P<.001) and were more likely to achieve their facility Kt/V goal (62% vs 42%; P =.01). Intervention patients also had nearly 3-fold larger increases in dialysis prescription (+0.16 vs +0.06; P<.001) and were 4 times more likely to change from use of catheters to use of fistulas/grafts (28% vs 7%; P =.04).\n An intervention tailored to patient-specific barriers resulted in increased hemodialysis dose. Extending this approach to the 33 000 persons in the United States receiving inadequate hemodialysis may substantially enhance patient survival, diminish hospitalizations, and decrease inpatient expenditures.", "To compare group versus individual academic detailing to increase diuretic or beta-blocker use in hypertension.\n We conducted a cluster-randomized controlled trial in a large health maintenance organization. Subjects (N=9820) were patients with newly treated hypertension in the year preceding the intervention (N=3692), the 9 months following the intervention (N=3556), and the second year following intervention (N=2572). We randomly allocated 3 practice sites to group detailing (N=227 prescribers), 3 to individual detailing (N=235 prescribers), and 3 to usual care (N=319 prescribers). Individual detailing entailed a physician-educator meeting individually with clinicians to address barriers to prescribing guideline-recommended medications. The group detailing intervention incorporated the same social marketing principles in small groups of clinicians.\n In the first year following the intervention, the rates of diuretic or beta-blocker use increased by 13.2% in the group detailing practices, 12.5% in the individual detailing practices, and 6.2% in the usual care practices. As compared with usual care practices, diuretic or beta-blocker use was more likely in group detailing practices (adjusted odds ratio (OR), 1.40; 95% confidence interval (CI), 1.11 - 1.76) and individual detailing practices (adjusted OR, 1.30; 95% CI, 0.95 - 1.79). Neither intervention affected blood pressure control. Two years following this single-visit intervention, there was still a trend suggesting a persistent effect of individual (OR, 1.22; 95% CI, 0.92 - 1.62), but not group, detailing (OR, 1.06; 95% CI, 0.80 - 1.39), as compared with usual care.\n Both group and individual academic detailing improved antihypertensive prescribing over and above usual care but may require reinforcement to sustain improvements.", "Recent studies have shown that lack of continuing primary care for asthma is associated with increased levels of morbidity in low-income minority children. Although effective preventive therapy is available, many African-American and Latino children receive episodic treatment for asthma that does not follow current guidelines for care. To see if access, continuity, and quality of care could be improved in pediatric clinics serving low-income children in New York City, we trained staff in New York City Bureau of Child Health clinics to provide continuing, preventive care for asthma.\n We evaluated the impact of the intervention over a 2-year period in a controlled study of 22 clinics. Training for intervention clinic staff was based on National Asthma Education and Prevention Program guidelines for the diagnosis and management of asthma, and included screening to identify new cases and health education to improve family management. The intervention included strong administrative support by the Bureau of Child Health to promote staff behavior change. We hypothesized that after the intervention, clinics that received the intervention would, compared with control clinics, have increased numbers of children with asthma receiving continuing care in the clinics and increased staff use of new pharmacologic and educational treatment methods.\n In both the first and second follow-up years, the intervention clinics had greater positive changes than control clinics on measures of access, continuity, and quality of care. For second year follow-up data these include: for access, greater rate of new asthma patients (40/1000 vs 16/1000; P < .01); for continuity, greater percentage of asthma patients returning for treatment 2 years in a row (42% vs 12%; P < .001) and greater annual frequency of scheduled visits for asthma per patient (1.85 vs .88; P < .001); and for quality, greater percentage of patients receiving inhaled beta agonists (52% vs 15%; P < .001) and inhaled antiinflammatory drugs (25% vs 2%; P < .001), and greater percentages of parents who reported receiving patient education on 12 topics from Bureau of Child Health physicians (71% vs 58%; P < .01) and nurses (61% vs 44%; P < .05).\n We conclude that the intervention substantially increased the Bureau of Child Health staff's ability to identify children with asthma, involve them in continuing care, and provide them with state-of-the-art care for asthma.", "A dissemination intervention to facilitate adoption of a preventive practice guideline (influenza vaccination for older adults) in group practices was developed and evaluated. The intervention, small-group consensus process, started with a physician expert presenting the guideline and followed with the group participating in a structured discussion of ways to implement the guideline that culminated in a public commitment (ie, \"buy in\") to adopt the guideline.\n Thirteen group practices and their primary care physicians (mean size, 5) were assigned randomly to intervention or control arms. In each group practice, physicians in the intervention arm met for 1 hour. Control physicians participated in an unrelated discussion (non-steroidal drug use). Guideline adoption was determined by changes in physicians' vaccination rates that were obtained through prechart and postchart reviews of 51 physicians. Prequestionnaires and postquestionnaires measured influenza knowledge and prevention attitudes.\n Using analysis of covariance, the small-group consensus process was found to increase physician vaccination rates by 34% compared with the control arm (F (1,48) = 19.49). All intervention arm physicians increased vaccination rates from before to after compared with 54% of control arm physicians. Attitudes and knowledge did not change and were unrelated to increased vaccination rates.\n A case is made for the small-group consensus process as an effective utilization-focused dissemination method. Interventions based on group dynamics and sensitive to local practice contexts can be useful in facilitating adoption of guidelines by physicians in group practices.", "Facilitate primary care physicians' compliance with recommended standards of care for late life depression by reducing barriers to recognition and treatment.\n Randomized controlled clinical trial of physician-targeted interventions.\n Academic primary care group practice caring for an urban, medically indigent patient population.\n Patients aged 60 and older who exceeded the threshold on the Centers for Epidemiologic Studies Depression Scale (CES-D) and the Hamilton Depression Rating Scale (HAM-D) and their primary care physicians.\n Physicians of intervention patients were provided with patient-specific treatment recommendations during 3 special visits scheduled specifically to address the patient's symptoms of depression. In general, physicians were encouraged to establish a diagnosis of depression and educate their patient about the diagnosis, discontinue medications that can cause or exacerbate depressive symptoms, initiate antidepressants when appropriate, and consider referral to psychiatry. Guidelines for prescribing antidepressants were provided. Control physicians received no intervention, and control patients received usual care.\n Frequency of recording a depression diagnosis, stopping medications associated with depression, initiating antidepressant medication, and psychiatry referral; mean changes in HAM-D and Sickness Impact Profile (SIP) scores.\n One hundred three physicians and 175 patients were involved in the clinical trial. Physicians of intervention patients were more likely to diagnose depression and prescribe antidepressants (P < 0.01). There were no differences between the groups in the frequency of stopping medications associated with depression or referrals to psychiatry. Medications with the strongest cause and effect relationship to depression were infrequently used in this cohort of patients. Although both groups showed improvement in HAM-D and SIP scores, we were unable to demonstrate significant differences in HAM-D or SIP scores between the 2 groups.\n Intensive screening and feedback of patient-specific treatment recommendations increased the recognition and treatment of late life depression by primary care physicians. However, we were unable to demonstrate significant improvement in depression or disability severity among intervention patients despite the informational support provided to their physicians. Efforts to improve the functional status of these patients may require more integrated interventions and more aggressive attempts to target psychosocial stressors traditionally outside the purview of primary care." ]

[ "17482611", "2642812", "8554435", "2065789", "3311134", "2185042" ]

[ "Effectiveness of intrauterine insemination in subfertile couples with an isolated cervical factor: a randomized clinical trial.", "Intrauterine insemination of washed husband's spermatozoa: a controlled study.", "Higher pregnancy rates following treatment of cervical factor with intrauterine insemination without superovulation versus intercourse: the importance of a well-timed postcoital test for infertility.", "A prospective trial of intrauterine insemination of motile spermatozoa versus timed intercourse.", "The value of artificial insemination with husband's semen in infertility due to failure of postcoital sperm-mucus penetration--controlled trial of treatment.", "Intrauterine insemination does and clomiphene citrate does not improve fecundity in couples with infertility due to male or idiopathic factors: a prospective, randomized, controlled study." ]

[ "After randomization of subfertile couples with an isolated cervical factor to intrauterine insemination for 6 months or expectant management for 6 months, 26 women (51%) vs. 16 women (33%) conceived, respectively. Of these pregnancies, 22 (43%) vs. 13 (27%) were ongoing (relative risk, 1.6; 95% confidence interval, 0.91 to 2.8). There was one multiple pregnancy in the group that was allocated to intrauterine insemination. This trial suggests a beneficial effect of IUI in couples with an isolated cervical factor.", "We performed intrauterine insemination with washed husband's spermatozoa in 27 couples with clear evidence of impaired sperm mucus interaction due to cervical hostility or immunologic male subfertility and in 30 couples with subnormal semen, but optimal cervical mucus qualities. In each couple insemination cycles were alternated with cycles during which normal intercourse took place. Both types of cycles were monitored for LH. When a clear rise of LH levels could be detected, either IUI was scheduled or intercourse advised for the following day. In the male subfertility group no difference between the pregnancy rates of insemination and intercourse cycles was present. In the group with impairment of sperm-mucus interaction, the pregnancy rate of the insemination cycles was 16%, whereas no pregnancies occurred during intercourse cycles.", "A randomized study comparing the efficacy of timed intrauterine insemination (IUI) without hyperstimulation to sexual intercourse was performed in women with cervical factor infertility. Among the strict requirements for inclusion in the study were a normal semen analysis in the male partner, as well as the failure to demonstrate any sperm with progressive forward motion in a postcoital test performed 8-12 h after intercourse at the time of a mature follicle. All other infertility factors were negative. The data demonstrated a statistically significant fecundity rate at 1 month when IUI was compared to intercourse (21.2 vs. 3.9%). These data suggest that carefully timed IUI in nonhyperstimulated cycles is an effective treatment for cervical factor infertility.", "The efficacy of intrauterine insemination (IUI) of selected motile sperm.\n Prospective randomized sequential alternating cycle trial comparing IUI with luteinizing hormone (LH)-timed intercourse.\n Clinical infertility service.\n Couples selected included unexplained infertility (n = 73), cervical mucus hostility (n = 24), moderate semen defect (n = 110), and severe semen defect (n = 78). Two hundred eighty-five couples undertook 600 IUI cycles and 505 LH-timed intercourse.\n Overall, IUI was slightly more effective than LH-timed intercourse with a pregnancy rate of 6.2% versus 3.4% per cycle. When individual categories were considered only, IUI for severe semen defect was significantly better (5.6% versus 1.3%, P less than 0.05). The first IUI cycle was more effective when compared with both subsequent IUI cycles and the initial LH-timed cycle. Overall, 74% (27/37) of IUI pregnancies occurred in the first cycle.\n Compared with LH-timed intercourse, IUI provided little or no improved expectation of pregnancy but was beneficial in couples with severe semen defect. The occurrence of pregnancy was limited per cycle and confined essentially to the initial cycle of treatment. Continued IUI is considered to be unrewarding.", "Artificial insemination with husband's semen into the cervical canal and uterine cavity (high AIH) was assessed by a randomized controlled prospective study in 46 couples whose infertility was due to failure of sperm mucus penetration, as defined by negative postcoital tests, after excluding all interfering female factors and men with sperm density less than 1 x 10(6)/ml. Seminal analysis was abnormal in 18 of the 46 men and sperm antibodies in semen were detected in 19 of the remaining 28 with normal seminal analysis. Overall, the cumulative conception rate after 6 months with AIH was 4.7 (SE 3.8)% and without treatment was 6.6 (SE 3.9)%. The results were unaffected by the findings on seminal analysis or by the presence or absence of sperm antibodies in semen. AIH appeared to be of no benefit.", "In the present prospective study we compared, in terms of pregnancy rates, the differences between intrauterine insemination (IUI) of in vitro capacitated husband's semen and timed natural intercourse in spontaneous or clomiphene citrate (CC) stimulated cycles. A rapid urinary luteinizing hormone peak detection test was used for timing of ovulation. Forty patients suffering from longstanding infertility of male (n = 17), cervical (n = 2), and idiopathic (n = 21) origin were randomly assigned into four distinct treatment modalities during 4 consecutive cycles. A total of 132 cycles were analyzed. In 35 cycles treated with CC plus IUI, five conceptions were achieved, whereas three pregnancies occurred in 32 inseminated spontaneous cycles. Only 1 patient conceived after timed intercourse in 31 CC stimulated cycles, and no pregnancy resulted from 34 spontaneous cycles combined with timed intercourse. There was a statistically significant higher conception rate in cycles in which IUI was performed, whereas the use of CC does not seem to improve the pregnancy rate. Analysis of results for other modifying factors did not substantially affect the relative risk (odds ratio) of pregnancy." ]

[ "11978675", "15277154", "16864756", "12912783", "15883418", "8017337" ]

[ "Five-week, low-glycemic index diet decreases total fat mass and improves plasma lipid profile in moderately overweight nondiabetic men.", "No difference in body weight decrease between a low-glycemic-index and a high-glycemic-index diet but reduced LDL cholesterol after 10-wk ad libitum intake of the low-glycemic-index diet.", "Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial.", "A reduced-glycemic load diet in the treatment of adolescent obesity.", "Effects of an ad libitum low-glycemic load diet on cardiovascular disease risk factors in obese young adults.", "Effects of a low-insulin-response, energy-restricted diet on weight loss and plasma insulin concentrations in hyperinsulinemic obese females." ]

[ "To evaluate whether a 5-week low-glycemic index (LGI) diet versus a high-glycemic index (HGI) diet can modify glucose and lipid metabolism as well as total fat mass in nondiabetic men.\n In this study, 11 healthy men were randomly allocated to 5 weeks of an LGI or HGI diet separated by a 5-week washout interval in a crossover design.\n The LGI diet resulted in lower postprandial plasma glucose and insulin profiles and areas under the curve (AUCs) than the HGI diet. A 5-week period of the LGI diet lowered plasma triacylglycerol excursion after lunch (AUC, P < 0.05 LGI vs. HGI). These modifications were associated with a decrease in the total fat mass by approximately 700 g (P < 0.05) and a tendency to increase lean body mass (P < 0.07) without any change in body weight. This decrease in fat mass was accompanied by a decrease in leptin, lipoprotein lipase, and hormone-sensitive lipase RNAm quantities in the subcutaneous abdominal adipose tissue (P < 0.05).\n We concluded that 5 weeks of an LGI diet ameliorates some plasma lipid parameters, decreases total fat mass, and tends to increase lean body mass without changing body weight. These changes were accompanied by a decrease in the expression of some genes implicated in lipid metabolism. Such a diet could be of benefit to healthy, slightly overweight subjects and might play a role in the prevention of metabolic diseases and their cardiovascular complications.", "The role of glycemic index (GI) in appetite and body-weight regulation is still not clear.\n The objective of the study was to investigate the long-term effects of a low-fat, high-carbohydrate diet with either low glycemic index (LGI) or high glycemic index (HGI) on ad libitum energy intake, body weight, and composition, as well as on risk factors for type 2 diabetes and ischemic heart disease in overweight healthy subjects.\n The study was a 10-wk parallel, randomized, intervention trial with 2 matched groups. The LGI or HGI test foods, given as replacements for the subjects' usual carbohydrate-rich foods, were equal in total energy, energy density, dietary fiber, and macronutrient composition. Subjects were 45 (LGI diet: n = 23; HGI diet: n = 22) healthy overweight [body mass index (in kg/m(2)): 27.6 +/- 0.2] women aged 20-40 y.\n Energy intake, mean (+/- SEM) body weight (LGI diet: -1.9 +/- 0.5 kg; HGI diet: -1.3 +/- 0.3 kg), and fat mass (LGI diet: -1.0 +/- 0.4 kg; HGI diet: -0.4 +/- 0.3 kg) decreased over time, but the differences between groups were not significant. No significant differences were observed between groups in fasting serum insulin, homeostasis model assessment for relative insulin resistance, homeostasis model assessment for beta cell function, triacylglycerol, nonesterified fatty acids, or HDL cholesterol. However, a 10% decrease in LDL cholesterol (P < 0.05) and a tendency to a larger decrease in total cholesterol (P = 0.06) were observed with consumption of the LGI diet as compared with the HGI diet.\n This study does not support the contention that low-fat LGI diets are more beneficial than HGI diets with regard to appetite or body-weight regulation as evaluated over 10 wk. However, it confirms previous findings of a beneficial effect of LGI diets on risk factors for ischemic heart disease.", "Despite the popularity of low-glycemic index (GI) and high-protein diets, to our knowledge no randomized, controlled trials have systematically compared their relative effects on weight loss and cardiovascular risk.\n A total of 129 overweight or obese young adults (body mass index, > or =25 [calculated as weight in kilograms divided by the square of height in meters]) were assigned to 1 of 4 reduced-fat, high-fiber diets for 12 weeks. Diets 1 and 2 were high carbohydrate (55% of total energy intake), with high and low GIs, respectively; diets 3 and 4 were high protein (25% of total energy intake), with high and low GIs, respectively. The glycemic load was highest in diet 1 and lowest in diet 4. Changes in weight, body composition, and blood chemistry profile were studied.\n While all groups lost a similar mean +/- SE percentage of weight (diet 1, -4.2% +/- 0.6%; diet 2, -5.5% +/- 0.5%; diet 3, -6.2% +/- 0.4%; and diet 4, -4.8% +/- 0.7%; P = .09), the proportion of subjects in each group who lost 5% or more of body weight varied significantly by diet (diet 1, 31%; diet 2, 56%; diet 3, 66%; and diet 4, 33%; P = .01). Women on diets 2 and 3 lost approximately 80% more fat mass (-4.5 +/- 0.5 [mean +/- SE] kg and -4.6 +/- 0.5 kg) than those on diet 1 (-2.5 +/- 0.5 kg; P = .007). Mean +/- SE low-density-lipoprotein cholesterol levels declined significantly in the diet 2 group (-6.6 +/- 3.9 mg/dL [-0.17 +/- 0.10 mmol/L]) but increased in the diet 3 group (+10.0 +/- 3.9 mg/dL [+0.26 +/- 0.10 mmol/L]; P = .02). Goals for energy distribution were not achieved exactly: both carbohydrate groups ate less fat, and the diet 2 group ate more fiber.\n Both high-protein and low-GI regimens increase body fat loss, but cardiovascular risk reduction is optimized by a high-carbohydrate, low-GI diet.", "The incidence of type 2 diabetes increases markedly for obese children after puberty. However, the effect of dietary composition on body weight and diabetes risk factors has not been studied in adolescents.\n To compare the effects of an ad libitum, reduced-glycemic load (GL) diet with those of an energy-restricted, reduced-fat diet in obese adolescents.\n Randomized control trial consisting of a 6-month intervention and a 6-month follow-up.\n Body composition (body mass index [BMI; calculated as weight in kilograms divided by the square of height in meters] and fat mass) and insulin resistance (homeostasis model assessment) were measured at 0, 6, and 12 months. Seven-day food diaries were used as a process measure.\n Sixteen obese adolescents aged 13 to 21 years. Intervention Experimental (reduced-GL) treatment emphasized selection of foods characterized by a low to moderate glycemic index, with 45% to 50% of energy from carbohydrates and 30% to 35% from fat. In contrast, conventional (reduced-fat) treatment emphasized selection of low-fat products, with 55% to 60% of energy from carbohydrates and 25% to 30% from fat.\n Fourteen subjects completed the study (7 per group). The GL decreased significantly in the experimental group, and dietary fat decreased significantly in the conventional group (P<.05 for both). At 12 months, mean +/- SEM BMI (-1.3 +/- 0.7 vs 0.7 +/- 0.5; P =.02) and fat mass (-3.0 +/- 1.6 vs 1.8 +/- 1.0 kg; P =.01) had decreased more in the experimental compared with the conventional group, differences that were materially unchanged in an intention-to-treat model (n = 16) (BMI, P =.02; fat mass, P =.01). Insulin resistance as measured by means of homeostasis model assessment increased less in the experimental group during the intervention period (-0.4 +/- 0.9 vs 2.6 +/- 1.2; P =.02). In post hoc analyses, GL was a significant predictor of treatment response among both groups (R2 = 0.51; P =.006), whereas dietary fat was not (R2 = 0.14; P =.22).\n An ad libitum reduced-GL diet appears to be a promising alternative to a conventional diet in obese adolescents. Large-scale randomized controlled trials are needed to further evaluate the effectiveness of reduced-GL and -glycemic index diets in the treatment of obesity and prevention of type 2 diabetes.", "The optimal nutritional approach for the prevention of cardiovascular disease among obese persons remains a topic of intense controversy. Available approaches range from conventional low-fat to very-low-carbohydrate diets.\n The aim of this pilot study was to evaluate the efficacy of an ad libitum low-glycemic load diet, without strict limitation on carbohydrate intake, as an alternative to a conventional low-fat diet.\n A randomized controlled trial compared 2 dietary treatments in obese young adults (n = 23) over 12 mo. The experimental treatment emphasized ad libitum consumption of low-glycemic-index foods, with 45-50% of energy from carbohydrates and 30-35% from fat. The conventional treatment was restricted in energy (250-500 kcal/d deficit) and fat (<30% of energy), with 55-60% of energy from carbohydrate. We compared changes in study outcomes by repeated-measures analysis of log-transformed data and expressed the results as mean percentage change.\n Body weight decreased significantly over a 6-mo intensive intervention in both the experimental and conventional diet groups (-8.4% and -7.8%, respectively) and remained below baseline at 12 mo (-7.8% and -6.1%, respectively). The experimental diet group showed a significantly greater mean decline in plasma triacylglycerols than did the conventional diet group (-37.2% and -19.1%, respectively; P = 0.005). Mean plasminogen activator inhibitor 1 concentrations decreased (-39.0%) in the experimental diet group but increased (33.1%) in the conventional diet group (P = 0.004). Changes in cholesterol concentrations, blood pressure, and insulin sensitivity did not differ significantly between the groups.\n An ad libitum low-glycemic load diet may be more efficacious than a conventional, energy-restricted, low-fat diet in reducing cardiovascular disease risk.", "The effects of two low-energy diets on serum insulin concentrations and weight loss in obese hyperinsulinemic females were compared during a 12-wk period. The first diet (n = 15) was designed to evoke a low insulin response (ID), and the second (n = 15) was a conventionally balanced diet (ND). After a 12-wk washout period, seven and nine subjects who had been on the ID and ND, respectively, changed to the alternative diet for 12 wk. Variables studied were basal and 30- and 120-min concentrations of blood glucose, insulin, and C-peptide after an oral glucose load; body weight; and energy intake. Mean (+/- SD) weight was significantly reduced after ID and ND (9.35 +/- 2.49 and 7.41 +/- 4.23, respectively). The mean weight loss was more after ID. Fasting insulin concentrations decreased more after ID compared with ND (91.3 +/- 61.8 vs 21.0 +/- 71.5 pmol/L; P < 0.05). We conclude that ID significantly reduces serum insulin concentrations and weight in obese hyperinsulinemic females." ]

[ "9287924", "4600626", "9352691", "3304522", "8986564", "3885668", "11607900", "7136436", "8184644", "11578347", "567753", "3822295", "1938446", "7489167", "4007463" ]

[ "A prospective randomized controlled trial comparing suprapubic with urethral catheterization in rectal surgery.", "Management of bladder drainage following vaginal plastic repairs.", "A prospective, randomized trial comparing continuous bladder drainage with catheterization at abdominal hysterectomy.", "Prospective randomized controlled trial of urethral versus suprapubic catheterization.", "Bladder management after total joint arthroplasty.", "Suprapubic versus transurethral bladder drainage after colposuspension/vaginal repair.", "Total joint arthroplasty and incidence of postoperative bacteriuria with an indwelling catheter or intermittent catheterization with one-dose antibiotic prophylaxis: a prospective randomized trial.", "A comparison of suprapubic and transurethral drainage for postoperative urinary retention in general surgical patients.", "Bacteriuria during urinary tract catheterization: suprapubic versus urethral route: a prospective randomized trial.", "Urinary drainage following radical hysterectomy for cervical carcinoma - a pilot comparison of urethral and suprapubic routes.", "[The indwelling catheter in gynecology and the development of bacteriuria; a comparative study of patients with the transurethral and the suprapubic catheter].", "Suprapubic versus transurethral bladder drainage after surgery for stress urinary incontinence.", "[Urinary catheterization: transurethral or suprapubic approach?].", "Optimum method for urinary drainage in major abdominal surgery: a prospective randomized trial of suprapubic versus urethral catheterization.", "[Suprapubic urinary diversion following gynecologic operations]." ]

[ "Bladder drainage is necessary for several days following rectal surgery. Urethral catheterization has long been known to be associated with significant morbidity. Therefore a prospective randomized trial was performed to determine if this morbidity could be decreased by suprapubic catheterization.\n One hundred and thirty-seven patients undergoing rectal surgery were prospectively randomized to either suprapubic or urethral catheterization.\n After exclusions, 108 patients were analysed. Of the 49 patients with suprapubic catheters there was 14% morbidity, and of the 59 patients with urethral catheters there was 32% morbidity. Significant bacteriuria was halved with suprapubic catheterization. Patient acceptability of suprapubic catheterization was high, and there was no increased morbidity in any of the areas studied.\n This study suggests that suprapubic catheterization has advantages over urethral catheterization with decreased bacteriuria, and greater patient acceptability. However, the significance of decreased bacteriuria is not clear and therefore we can only say suprapubic catheter drainage is comparable to urethral catheter drainage.", "nan", "To compare the infection rate and post-operative morbidity between in-dwelling urinary catheterization and 'in-out' catheterization at the time of routine total abdominal hysterectomy.\n The study comprised 100 patients who were blindly randomized to have either an indwelling Foley catheter or an 'in-out' catheterization at the time of surgery. Follow-up data on the retention of urine, urinary symptoms and infection were obtained.\n Of the 95 patients with complete data, 36% of those undergoing in-out catheterization had urinary retention after operation, requiring bladder emptying, compared with 4% of those receiving an indwelling catheter (P < 0.001). In addition, 29% of the catheterized group had urinary tract bacteriuria compared with 13% of the uncatheterized group (P < 0.025).\n This randomized controlled trial showed that in-out urinary catheterization at the time of routine abdominal hysterectomy was associated with a significantly higher incidence of post-operative urinary retention compared with in-dwelling catheterization, and may have implications for long-term bladder function.", "Sixty-six patients requiring catheterization in the course of general surgical operations were randomly allocated into two groups. Of the 34 patients catheterized urethrally 16 developed urinary tract infections whereas of the 32 suprapubically catheterized patients only 2 developed an infection (P less than 0.001). Five patients required recatheterization after removal of their urethral catheters. There were no major complications associated with the use of suprapubic catheters. We propose that, when catheterization is required during a general surgical procedure, the suprapubic route is to be preferred.", "This study was undertaken to determine the impact of an indwelling Foley catheter on bladder dysfunction and incidence of urinary tract infections after total joint arthroplasty. A prospective randomized controlled trial was conducted assigning use of an indwelling Foley catheter (group 1) or intermittent catheterization (group 2) for 48 hours following operation. Postoperative cultures were obtained on days 2 and 5, and the number of intermittent catheterization events and void and catheterization volumes were recorded. Concurrent cost-effectiveness analysis was conducted. One hundred nineteen of 174 consecutive patients having elective primary total joint arthroplasty completed the study. Five of 62 patients (8%) in group 1 and 7 of 57 patients (12%) in group 2 developed urinary tract infections (NS, P = 45). Twenty patients (35%) in group 2 and 12 (19%) in group 1 required straight catheterization for inability to void 48 hours after surgery (P = .05). Seventeen patients (35%) in group 2 and eight patients (16%) in group 1 required straight catheterization after epidural analgesia was discontinued (P = .024). Bladder management by indwelling Foley catheter saved more than 150 minutes of direct nursing contact per patient and $3,000 in total hospital costs. Indwelling Foley catheters reduced the frequency of postoperative urinary retention, were less labor intensive than intermittent straight catheterization, and were not associated with an increased risk of urinary infection. In the setting of epidural anesthesia and postoperative analgesia for total joint arthroplasty, management by indwelling catheter is a cost-effective strategy to facilitate postoperative return of normal bladder function.", "Ninety-two patients with preoperative sterile urine undergoing colposuspension or vaginal repair operation for stress urinary incontinence and/or genital descensus were randomized to either suprapubic or transurethral postoperative catheter drainage. The prevalence of significant bacteriuria on the fifth postoperative day was statistically significantly lower when using suprapubic catheter (20.8%) than with transurethral catheter drainage (45.5%). This applied especially to colposuspension. The rate of postoperatively impaired bladder emptying also tended to be reduced when using suprapubic catheter. At follow-up after one year, postoperative bacteriuria was closely correlated to increased rates of both clinical cystitis and asymptomatic significant bacteriuria. Thus it is recommended to use suprapubic bladder drainage not only after colposuspension but also after vaginal repair in an effort to avoid an increased risk of urinary infections.", "This study examined the difference in postoperative bacteriuria in total joint arthroplasty after use of either an indwelling catheter or intermittent catheterization. Previous studies showed a preference for an indwelling catheter over intermittent catheterization to resolve postoperative urinary retention in total joint arthroplasty, but these studies generally used 48 hours of antibiotic prophylaxis. Increasing awareness of costs and bacterial resistance to antibiotics have prompted many centers to reduce prophylaxis to only 1 preoperative dose A prospective, randomized, controlled trial was conducted in primary total hip and primary total knee arthroplasty patients. One dose of cefazolin, 1 g, was administered intravenously immediately preoperatively. Five of 13 (38%) men in the indwelling catheter group and 0 of 14 (0%) men in the intermittent catheterization group developed postoperative bacteriuria (P =.016), and 6 of 33 (18%) women in the indwelling catheter group and 3 of 39 (8%) women in the intermittent catheterization group developed postoperative bacteriuria (not significant). A total of 11 (24%) patients in the indwelling catheter group (n = 46) and 3 (6%) patients in the intermittent catheterization group (n = 53) developed postoperative bacteriuria (P =.018). In this setting with 1-dose antibiotic prophylaxis, intermittent catheterization resulted in a lower incidence of postoperative bacteriuria compared with an indwelling catheter. For men, this difference is significant.", "Percutaneous suprapubic bladder drainage, using an indwelling Silastic catheter, was compared with transurethral catheterization for the management of postoperative urinary retention in general surgical patients. In a prospective controlled trail, the overall incidence of postoperative retention was 7%. The urinary infection rate was 70% with transurethral catheterization and 8% with suprapubic drainage. Patients accepted suprapubic damage much more readily than transurethral cateterization and both medical and nursing personnel found the former method easier to manage effectively. Also, the patients' ability to pass urine spontaneously could be assessed without removing the catheter. However, minor mechanical complications were more common with suprapubic drainage. The cost of the two systems is comparable. We conclude that the routine use of suprapubic catheter drainage in the management of postoperative urinary retention significantly reduces the incidence of infection and is the preferred method of treating this common complication.", "In this randomized prospective trial urethral and suprapubic routes were compared in terms of tolerance and infectious potential. Daily bacteriuria determined infectious danger and patients were interrogated on the pain and discomfort induced by their catheter every day. Identical single dose pre-operative antibiotic prophylaxis was routinely applied. Patients (n = 50) were divided into two similar groups (25 suprapubic catheters and 25 urethral catheters). Four patients in the suprapubic group were excluded. All specimen cultured by suprapubic catheter remained sterile. Nine patients with urethral catheterization eventually developed bacteriuria. The difference became significant on the third day of catheterization (p < 0.05) and increased on days 4 and 5 (p < 0.01). Between the two groups, pain and discomfort did not achieve statistical significance. Suprapubic catheterization is preferable to the alternative using the urethral route in terms of improving urine sterility.", "Twenty-four patients who underwent radical hysterectomy and pelvic node dissection for cervical carcinoma were randomized in a pilot study to compare continuous postoperative drainage by urethral and suprapubic catheters. There were no statistically significant differences in either the duration of continuous catheter drainage before the return of spontaneous voiding or the incidence of urinary tract infection in the two groups. Power calculations reveal that 628 patients require to be entered into each arm of a future study in order to be able to detect the former difference should it exist (alpha = 0.05, beta = 0.2, difference = 16% of one s.d.) and 41 in the latter (alpha = 0.05, beta = 0.2, 92.9% urethral group had UTI, 70% suprapubic group had UTI). We conclude that differences in these objective measures of catheter efficacy and morbidity between the groups, if they exist, are clinically irrelevant. On this basis we suggest that individual gynaecological oncologists should continue to use whichever method of catheter drainage best suits their clinical practice.", "nan", "Fifty-one patients with clinical and urodynamic diagnoses of stress urinary incontinence were randomly allocated to either suprapubic (N = 24) or transurethral (N = 27) bladder drainage after vaginal surgery for stress incontinence (revised Pereyra procedure). Postoperative use of suprapubic bladder drainage significantly reduced febrile morbidity (calculated as fever index; P less than .01) and length of hospitalization (P less than .05). Postoperative normal bladder functions resumed more quickly when suprapubic drainage was used (P less than .05), so that most patients did not need bladder catheterization upon discharge, as opposed to more than half of those with Foley catheters, who left the hospital with a catheter in place (P less than .05). We conclude that it is both beneficial and cost-effective to use suprapubic bladder drainage after a Pereyra operation for stress urinary incontinence.", "75 patients, needing a bladder drainage for nonurological indications and having sterile urines were studied after randomization into two groups. In the first group, drained with an urethral catheter, urinary infection took place in 12 (= 30%) patients, while it was detected in 4 (= 11%) drained with a suprapubic catheter. In this latter group, patients felt more comfortable, had less pain; the duration of urinary drainage and hospital stay was shorter.", "The outcome of suprapubic and urethral catheterization in abdominal surgery was compared in a prospective randomized trial. Twenty-eight patients received a suprapubic and 29 a urethral catheter. The groups were similar in terms of age, sex, operation performed and postoperative analgesia. There was no difference in the duration of catheterization (suprapubic: median 5 (range 4-10) days; urethral: median 4 (range 2-11) days). Urinary sepsis occurred in three patients in each group. Urethral catheters caused pain in significantly more patients (urethral 13; suprapubic two; chi 2 = 8.6, 1 d.f. P < 0.01), on more days (suprapubic: 6 of 142 catheter days; urethral: 37 of 126 catheter days; chi 2 = 29.5, 1 d.f. P < 0.001). Two men with urethral catheters and one with a suprapubic catheter failed to void urethrally when required to do so. Suprapubic catheterization is the method of choice for urinary drainage when this is required in abdominal surgery.", "In a prospective study the results of postoperative urinary discharge by suprapubic catheterisation (SC) are compared with those of transurethral catheterisation (TC) in a randomised collective of gynaecological patients after vaginal hysterectomy with front (resp. front and back) plastic. During November 1979 and September 1980 157 patients were examined, 88 patients by suprapubic catheterisation and 69 by transurethral catheterisation, with random distribution. Additionally, 430 other patients with suprapubic aspiration after vaginal hysterectomy with front and/or back plastic performed between September 1980 and October 1982 were examined retrospectively especially under the aspect of possible complications. The advantages of suprapubic urinary discharge are shown in the significantly reduced rate of primary infections. 20.5 per cent of infections are opposed to 67.1 per cent in the comparative group with TC. Spontaneous miction was possible in the SC group two days earlier than in the group of TC (5.2 days opposed to 7.35 days). Additional drug treatment for restitution of the bladder function was more often necessary for patients with TC, although the results with 43.5 per cent against 29.5 per cent in the SC collective are not significant. The number of renewed catheterisations after removal of the catheter was higher by 27 per cent in the group of patients with SC. Subjective complaints were stated by patients with TC in 66.7 per cent against 18.2 per cent of women with SC. This result is significant. In the TC collective there were significantly more patients with leucocyturia (88.5 per cent against 48.7 per cent). Antibiotic treatment of an urinary tract infection with typical symptoms was necessary in 35.8 per cent for patients with TC and in 14.1 per cent for women with SC.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "16088404", "19652068" ]

[ "Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19).", "Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia." ]

[ "The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma.\n A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles.\n The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP.\n Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.", "This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced (Binet stage B or C) chronic lymphocytic leukemia (CLL).\n Patients (<or= 75 years of age) were randomly assigned to receive bendamustine 100 mg/m(2)/d intravenously on days 1 to 2, or chlorambucil 0.8 mg/kg (Broca's normal weight) orally on days 1 and 15; treatment cycles were repeated every 4 weeks for a maximum of six cycles. The response to treatment was assessed according to National Cancer Institute Working Group criteria, and the final determination of response was made by a blinded independent review committee.\n A total of 319 patients were randomly assigned (162 bendamustine, 157 chlorambucil). Complete or partial responses were achieved in 110 (68%) of 162 bendamustine-treated and 48 (31%) of 157 chlorambucil-treated patients (P < .0001). More patients showed complete responses with bendamustine than with chlorambucil (31% v 2%). Median progression-free survival was 21.6 months with bendamustine and 8.3 months with chlorambucil (P < .0001). Bendamustine was also associated with an improvement in duration of remission, compared with chlorambucil (median, 21.8 v 8.0 months). Hematologic National Cancer Institute Common Toxicity Criteria grade 3 to 4 adverse events were more common with bendamustine than with chlorambucil (occurring in 40% v 19% of patients). Severe infections (grade 3 to 4) occurred in 8% of bendamustine-treated patients and 3% of chlorambucil-treated patients.\n Bendamustine offers significantly greater efficacy than chlorambucil, and a manageable toxicity profile, when used as first-line therapy in patients with advanced CLL." ]

[ "20156909", "21521389", "15753541" ]

[ "Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia.", "Poor tolerability of thalidomide in end-stage oesophageal cancer.", "Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial." ]

[ "A phase III, randomized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass (LBM), resting energy expenditure (REE), and fatigue-and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines.\n Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were randomly assigned to one of five treatment arms: arm 1, medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4, thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment duration was 4 months.\n Analysis of variance showed a significant difference between treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms.\n The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents.", "Oesophageal cancer cachexia is a significant clinical problem, resulting in excessive morbidity and mortality. In a pilot study, 10 patients with cachexia due to advanced cancer of the oesophagus gained weight, including lean tissue, after 14-day treatment with thalidomide. Here, we present randomised placebo controlled trial data over a 6-week period to test the hypothesis that thalidomide is superior to placebo in terms of weight gain in patients with cachexia caused by oesophageal cancer. Thalidomide, 200 mg daily, or an identical placebo was given to patients with advanced oesophageal cancer. Total body weight and lean body mass were assessed in addition to drug tolerability and performance indices. Thirty-four patients were recruited. Of these, six given thalidomide and 16 given placebo completed the protocol; all withdrawals were due to adverse drug reactions or complications of disease. Thalidomide showed no benefit over placebo in participants who completed the protocol. These data suggest that thalidomide is poorly tolerated in patients with advanced cancer of the oesophagus and may not ameliorate the progression of cachexia. In the absence of hard supportive evidence, off-licence treatment with thalidomide should be used with great caution as an adjunct to nutritional support in patients with advanced cancer.\n © 2011 Blackwell Publishing Ltd.", "Proinflammatory cytokines, especially tumour necrosis factor alpha (TNF-alpha), play a prominent role in the pathogenesis of cancer cachexia. Thalidomide, which is an inhibitor of TNF-alpha synthesis, may represent a novel and rational approach to the treatment of cancer cachexia.\n To assess the safety and efficacy of thalidomide in attenuating weight loss in patients with cachexia secondary to advanced pancreatic cancer.\n Fifty patients with advanced pancreatic cancer who had lost at least 10% of their body weight were randomised to receive thalidomide 200 mg daily or placebo for 24 weeks in a single centre, double blind, randomised controlled trial. The primary outcome was change in weight and nutritional status.\n Thirty three patients (16 control, 17 thalidomide) were evaluated at four weeks, and 20 patients (eight control, 12 thalidomide) at eight weeks. At four weeks, patients who received thalidomide had gained on average 0.37 kg in weight and 1.0 cm(3) in arm muscle mass (AMA) compared with a loss of 2.21 kg (absolute difference -2.59 kg (95% confidence interval (CI) -4.3 to -0.8); p = 0.005) and 4.46 cm(3) (absolute difference -5.6 cm(3) (95% CI -8.9 to -2.2); p = 0.002) in the placebo group. At eight weeks, patients in the thalidomide group had lost 0.06 kg in weight and 0.5 cm(3) in AMA compared with a loss of 3.62 kg (absolute difference -3.57 kg (95% CI -6.8 to -0.3); p = 0.034) and 8.4 cm(3) (absolute difference -7.9 cm(3) (95% CI -14.0 to -1.8); p = 0.014) in the placebo group. Improvement in physical functioning correlated positively with weight gain (r = 0.56, p = 0.001).\n Thalidomide was well tolerated and effective at attenuating loss of weight and lean body mass in patients with cachexia due to advanced pancreatic cancer." ]

[ "10548619", "17069813", "9627287", "18343810" ]

[ "Hydrosalpinx and IVF outcome: a prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF.", "Proximal tubal occlusion and salpingectomy result in similar improvement in in vitro fertilization outcome in patients with hydrosalpinx.", "Does previous salpingectomy improve implantation and pregnancy rates in patients with severe tubal factor infertility who are undergoing in vitro fertilization? A pilot prospective randomized study.", "Ultrasound-guided hydrosalpinx aspiration during oocyte collection improves pregnancy outcome in IVF: a randomized controlled trial." ]

[ "Many retrospective studies have shown that hydrosalpinx is associated with poor in-vitro fertilization (IVF) outcome. The mechanism of the actual cause is not yet fully understood. A clinical practice of performing salpingectomy before IVF has developed, without any evidence from prospective trials. The aim of the present prospective randomized trial was to test if a salpingectomy prior to IVF was effective in terms of increased pregnancy rates. Patients with hydrosalpinx were randomized to either a laparoscopic salpingectomy or no intervention before IVF. A total of 204 patients was available for an intention-to-treat analysis and 192 actually started IVF. Clinical pregnancy rates per included patient were 36.6% in the salpingectomy group and 23.9% in the non-intervention group (not significant, P = 0.067) and the ensuing delivery rates were 28.6% and 16.3% (P = 0.045). The corresponding delivery rates per transfer cycle were 29.5% versus 17. 5% (not significant, P = 0.083). A subgroup analysis revealed significant differences in favour of salpingectomy, in implantation rates in patients with bilateral hydrosalpinges (25.6% versus 12.3%, P = 0.038) and in clinical pregnancy rates (45.7% versus 22.5%, P = 0.029) and delivery rates (40.0% versus 17.5%, P = 0.038) in patients with ultrasound visible hydrosalpinges. The delivery rate was increased 3.5-fold in patients with bilateral hydrosalpinges visible on ultrasound (P = 0.019).", "To evaluate and compare the clinical impact of proximal tubal occlusion and salpingectomy when performed before IVF in patients with hydrosalpinges.\n Prospective randomized study.\n Assisted reproduction unit in an obstetrics and gynecology department in a university hospital in Greece as well as assisted reproduction unit in an urban clinic in a major city in Greece.\n One hundred fifteen patients with unilateral or bilateral hydrosalpinges who were candidates for IVF treatment.\n Laparoscopic proximal tubal occlusion, laparoscopic salpingectomy, controlled ovarian hyperstimulation, IVF, and embryo transfer.\n Implantation rate, clinical-pregnancy rate, ongoing-pregnancy rate, abortion rate, and ectopic-pregnancy rate.\n Patients who underwent proximal tubal occlusion before IVF demonstrated significantly increased implantation, clinical-pregnancy, and ongoing-pregnancy rates compared with those with no surgical intervention and demonstrated implantation, clinical-pregnancy, and ongoing-pregnancy rates comparable to those who underwent salpingectomy.\n Proximal tubal occlusion, when performed in women with unilateral or bilateral hydrosalpinges before their IVF treatment, represents a potentially beneficial surgical procedure, increasing significantly the chances for successful implantation and for clinical and ongoing pregnancy. Proximal tubal occlusion may be viewed as a valid alternative when salpingectomy is technically difficult or not feasible.", "To evaluate the implantation rate and pregnancy rate (PR) in patients with severe tubal factor infertility who were undergoing IVF. Patients who had undergone salpingectomy were compared with those who had not.\n A prospective randomized study.\n A department of obstetrics and gynecology at a university hospital.\n Thirty patients who previously had undergone salpingectomy and 30 patients who had not undergone salpingectomy before IVF treatment.\n Laparoscopy with or without salpingectomy followed by IVF with the use of combined GnRH agonist and hMG therapy in a long stimulation protocol.\n Embryo implantation rate and ongoing PR per transfer. The cumulative PRs were compared for the two groups of patients.\n After the first IVF attempt, the implantation rate was 10.4% in the group with salpingectomy and 4.6% in the group without salpingectomy. For all IVF attempts, the respective embryo implantation rates in the two groups were 13.4% and 8.6%. The ongoing PR per transfer was 34.2% in the group with salpingectomy compared with 18.7% in the group without salpingectomy. After four IVF attempts, the probability of becoming pregnant was greater in the group of patients with salpingectomy (75%) than in the group without salpingectomy (63%).\n Previous salpingectomy in patients with severe tubal factor infertility who are undergoing IVF seems to increase the embryo implantation rate and the PR per cycle of IVF. This monocentric study must be followed by other similar studies to allow for a metaanalysis and confirm this clear trend with definitive evidence.", "Hydrosalpinges have adverse effects on IVF outcomes. Salpingectomy is effective in improving outcomes, but it is not always practical or safe. Ultrasound-guided aspiration of hydrosalpinges at oocyte collection is an option for those who develop hydrosalpinges during controlled ovarian stimulation; however, there is no randomized evidence to show whether this practice is effective.\n Between October 1999 and June 2003, consenting women of age <or=39 years with an ultrasound diagnosis of hydrosalpinx were randomized before oocyte collection to transvaginal aspiration of hydrosalpinx under antibiotics cover or no aspiration. Third-party randomization was performed using a computer algorithm, and allocation concealment was achieved with opaque sealed envelopes. Outcomes were biochemical and clinical pregnancies, implantation, spontaneous abortion, ectopic pregnancy and pelvic infection rates. Analysis was by intention to treat.\n Sixty-six women were recruited to the trial, 32 to the aspiration group and 34 to the no-aspiration group. Aspiration resulted in a greater biochemical pregnancy rate [14/32 (43.8%) versus 7/34 (20.6%), relative risk (RR) = 2.1 (1.02, 4.6), P = 0.04]. Clinical pregnancy rates for aspiration versus control groups were 31.3% (10/32) and 17.6% (6/34), respectively [RR = 1.8 (0.8, 4.3), P = 0.20]. There were no changes in implantation rate or spontaneous abortion risk with aspiration and no differences between the groups in infection or ectopic pregnancy rates.\n In women who are identified to have hydrosalpinges during controlled ovarian stimulation during IVF, aspiration of hydrosalpinges during oocyte collection may be effective in improving pregnancy rates (Trial Registration Number: NCT00566956)." ]

[ "2657423", "9722255", "7752005", "16396863", "7700763", "2235226", "9545359", "15161992", "1881718", "3880879", "1421877", "10390255", "2651132", "2685220", "14512180" ]

[ "A controlled trial of dexamethasone in preterm infants at high risk for bronchopulmonary dysplasia.", "Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity.", "Effect of pulse dexamethasone therapy on the incidence and severity of chronic lung disease in the very low birth weight infant.", "Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized, controlled trial.", "Effects of early dexamethasone therapy on pulmonary mechanics and chronic lung disease in very low birth weight infants: a randomized, controlled trial.", "Dexamethasone effects on the hospital course of infants with bronchopulmonary dysplasia who are dependent on artificial ventilation.", "A multicenter trial of two dexamethasone regimens in ventilator-dependent premature infants.", "Effect of dexamethasone on tracheobronchial aspirate fluid cytology and pulmonary mechanics in preterm infants.", "Dexamethasone therapy in neonatal chronic lung disease: an international placebo-controlled trial. Collaborative Dexamethasone Trial Group.", "Controlled trial of dexamethasone in respirator-dependent infants with bronchopulmonary dysplasia.", "Randomized controlled trial of dexamethasone treatment in very-low-birth-weight infants with ventilator-dependent chronic lung disease.", "Randomized placebo-controlled trial of a 42-Day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants.", "Dexamethasone in neonatal chronic lung disease: pulmonary effects and intracranial complications.", "Dexamethasone therapy for chronic lung disease in ventilator- and oxygen-dependent infants: a controlled trial.", "Adrenal suppression and extubation rate after moderately early low-dose dexamethasone therapy in very preterm infants." ]

[ "We evaluated the use of dexamethasone in preterm infants to decrease morbidity associated with bronchopulmonary dysplasia in a randomized, double-blind, placebo-controlled trial. Thirty-six preterm infants (birth weight, less than or equal to 1250 g and gestational age, less than or equal to 30 weeks) who were dependent on oxygen and mechanical ventilation at two weeks of age received a 42-day course of dexamethasone (n = 13), an 18-day course of dexamethasone (n = 12), or saline placebo (n = 11). The starting dose of dexamethasone was 0.5 mg per kilogram of body weight per day, and it was progressively lowered during the period of administration. Infants in the 42-day dexamethasone group, but not those in the 18-day group, were weaned from mechanical ventilation significantly faster than control infants (medians 29, 73, and 84 days, respectively; P less than 0.05), and from supplemental oxygen (medians 65, 190, and 136 days, respectively; P less than 0.05). No clinical complications of steroid administration were noted. Follow-up of all 23 survivors at 6 and 15 months of age showed good outcome (normal neurologic examinations and Bayley Developmental Indexes greater than or equal to 84) in 7 of the 9 infants in the 42-day dexamethasone group, but in only 2 of the 9 infants in the 18-day dexamethasone group and 2 of the 5 in the placebo group (P less than 0.05). We conclude that dexamethasone therapy for 42 days improves pulmonary and neurodevelopmental outcome in very-low-birth-weight infants at high risk for bronchopulmonary dysplasia.", "In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD.", "We conducted a prospective, randomized, double-blind trial to assess the efficacy and safety of pulse doses of dexamethasone on survival without supplemental oxygen in very low birth weight infants at high risk of having chronic lung disease. Seventy-eight infants with birth weights < or = 1500 gm who were ventilator dependent at 7 days of postnatal age were randomly assigned to receive pulse doses of dexamethasone, 0.5 mg/kg per day, divided twice daily (n = 39), or an equivalent volume of saline solution placebo (n = 39), for 3 days at 10-day intervals until they no longer required supplemental oxygen or assisted ventilation, or reached 36 weeks of postmenstrual age. At study entry, the groups did not differ by birth weight, gestational age, or severity of lung disease. At 36 weeks of postmenstrual age, there was both a significant increase in survival rates without oxygen supplementation (p = 0.03) and a significant decrease in the incidence of chronic lung disease (p = 0.047) in the group that received pulse therapy. Supplemental oxygen requirements were less throughout the study period in the group that received repeated pulse doses of dexamethasone (p = 0.013). The total numbers of deaths and the durations of supplemental oxygen, ventilator support, and hospital stay did not differ between groups. Recorded side effects in the pulse therapy group were minimal and included an increase in the use of insulin therapy for hyperglycemia (p < 0.05). We conclude that in this population of very low birth weight infants, treatment with pulse doses of dexamethasone resulted in improvement in pulmonary outcome without clinically significant side effects.", "Postnatal corticosteroid therapy is controversial. The aim of this study was to determine the short-term effects of low-dose dexamethasone treatment among chronically ventilator-dependent neonates.\n Very preterm (gestational age: <28 weeks) or extremely low birth weight (birth weight: <1000 g) infants who were ventilator dependent after the first 1 week of life were eligible and were assigned randomly to receive masked dexamethasone (0.89 mg/kg over 10 days) or saline placebo. Data on ventilator and oxygen requirements and deaths were recorded.\n Seventy infants were recruited from 11 centers, at a median age of 23 days. More infants were extubated successfully by 10 days of treatment in the dexamethasone group (60%, 21 of 35 patients) than in the control group (12%, 4 of 34 patients) (odds ratio [OR]: 11.2; 95% confidence interval [CI]: 3.2-39.0). Ventilator and oxygen requirements improved substantially, and the duration of intubation was shorter. There was little evidence for a reduction in either the mortality rate (dexamethasone group: 11%; control group: 20%; OR: 0.52; 95% CI: 0.14-1.95) or the rate of oxygen dependence at 36 weeks (dexamethasone group: 85%; control group: 91%; OR: 0.58; 95% CI: 0.13-2.66). There were no obvious effects of low-dose dexamethasone on blood glucose concentrations, blood pressure, or other complications. No infant experienced intestinal perforation.\n Low-dose dexamethasone treatment after the first 1 week of life clearly facilitates extubation and shortens the duration of intubation among ventilator-dependent, very preterm/extremely low birth weight infants, without any obvious short-term complications. Combined with recent evidence that infants at very high risk of bronchopulmonary dysplasia may benefit in the long term, our study reopens debate regarding the role of low-dose, late postnatal, corticosteroid therapy.", "To determine the changes in pulmonary mechanics before and during early dexamethasone therapy, and to evaluate the effect of dexamethasone on the duration of mechanical ventilation in very low birth weight (VLBW) ventilator-dependent infants at risk for chronic lung disease (CLD).\n A prospective randomized trial was conducted. Forty-three patients (birth weight 600 to 1500 g, gestational age 24 to 32 weeks) who failed to be weaned from the respirator at 7 to 14 days of age were enrolled; 23 infants received a 7-day course of dexamethasone (0.5 mg/kg/day intravenously for 3 days, 0.25 mg/kg/day for 3 days, and 0.1 mg/kg/day for 1 day), and 20 patients were in the control group. At similar mean airway pressure (MAP) and fractional inspired oxygen concentration (FiO2), respiratory system mechanics were measured before and on days 2, 5, and 7 of the study. Airway pressure, flow and tidal volume (VT) were recorded and only mechanical breaths were analyzed. Respiratory compliance (Crs) and respiratory resistance (Rrs) were calculated by two factor least mean square analysis.\n Eighty-three percent of infants in the dexamethasone group and 90% in the control group received surfactant in the first 24 hours of life. There was a significant increase in Crs and VT in the dexamethasone group as compared with the control group (P < .001). No major changes in Rrs were observed. Dexamethasone therapy significantly decreased FiO2 and MAP P < .001) and facilitated successful weaning from mechanical ventilation. In addition to a shorter duration of mechanical ventilation (P < .01), the occurrence of CLD (FiO2 > 0.21 at 36 weeks of corrected gestational age, chest radiograph changes) was significantly decreased in the dexamethasone group (P < .01). Except for a transient increase in blood pressure and serum glucose, there were no significant differences in infection rates, intraventricular hemorrhage, or retinopathy of prematurity. Thirteen patients in the control group received dexamethasone at a later age.\n Our findings indicate that: 1) early dexamethasone therapy in VLBW infants markedly improves respiratory compliance and tidal volume, reduces FiO2 and MAP requirements, and facilitates extubation in these infants; 2) early dexamethasone therapy reduces the duration of mechanical ventilation and decreases CLD (at 28 days and 36 weeks) in a population of VLBW infants largely treated with surfactant.", "A randomized double-blind placebo-controlled trial was conducted to evaluate the effects of enterally administered dexamethasone on the hospital course of infants with bronchopulmonary dysplasia. A total of 23 infants with a birth weight less than 1500 g who were dependent on artificial ventilation 3 to 4 weeks of age received dexamethasone (n = 12) or saline placebo (n = 11). Dexamethasone (0.5 mg/kg per day) was given in tapering doses for 7 days followed by hydrocortisone (8 mg/kg per day) which was progressively reduced for a total of 17 days of therapy. Infants who received dexamethasone required less oxygen on days 8 and 17 (P less than .05) and were more likely to extubate 8 days after therapy than infants in the control group (respectively 8/12 vs 3/11 infants, P less than .05; P = .12 after Yates correction). The use of dexamethasone significantly shortened median duration of mechanical ventilation (4 vs 22 days, P less than .05) but had no effect on length of oxygen therapy, hospitalization, home oxygen therapy, occurrence and severity of retinopathy of prematurity, rate of growth, and mortality. No significant complications resulted from dexamethasone therapy. Measurements of plasma dexamethasone levels confirmed the absorption of drug from the gastrointestinal tract (23.7 ng/mL in dexamethasone vs 4.6 ng/mL in the control group, P less than .05). Dexamethasone administration resulted in short-term improvements in pulmonary function but did not ameliorate the hospital course of infants with bronchopulmonary dysplasia.", "Ventilator-dependent premature infants are often treated with dexamethasone. However, the optimal timing of therapy is unknown.\n We compared the benefits and hazards of initiating dexamethasone therapy at two weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth-weight infants (501 to 1500 g) who had respiratory index scores (mean airway pressure x the fraction of inspired oxygen) of 52.4 at two weeks of age. One hundred eighty-two infants received dexamethasone for two weeks followed by placebo for two weeks, and 189 infants received placebo for two weeks followed by either dexamethasone (those with a respiratory-index score of > or =2.4 on treatment day 14) or additional placebo for two weeks. Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five days, and the dose was then tapered.\n The median time to ventilator independence was 36 days in the dexamethasone-placebo group and 37 days in the placebo-dexamethasone group. The incidences of chronic lung disease (defined as the need for oxygen supplementation at 36 weeks' postconceptional age) were 66 percent and 67 percent, respectively. Dexamethasone was associated with an increased incidence of nosocomial bacteremia (relative risk, 1.5; 95 percent confidence interval, 1.1 to 2.1) and hyperglycemia (relative risk, 1.9; 95 percent confidence interval, 1.2 to 3.0) in the dexamethasone-placebo group, elevated blood pressure (relative risk, 2.9; 95 percent confidence interval, 1.2 to 6.9) in the placebo-dexamethasone group, and diminished weight gain and head growth (P< 0.001) in both groups.\n Treatment of ventilator-dependent premature infants with dexamethasone at two weeks of age is more hazardous and no more beneficial than treatment at four weeks of ages.", "The changes induced on respiratory mechanics and on tracheobronchial aspirate fluid (TAF) cytology by dexamethasone courses started at two different postnatal ages in preterm infants at risk of chronic lung disease (CLD) were reported in this clinical trial designed in two phases. The first phase of the study included 20 neonates with birth weight < or = 1,250 g and gestational age < or = 32 weeks, who were oxygen and ventilator dependent on the 10th day of life. They were randomly assigned to the moderately early dexamethasone (MED) group or to the control group. The second phase of the study included 20 neonates with the same characteristics, oxygen and ventilator dependent on the 4th day of life, randomly assigned to the early dexamethasone (ED) group or to the control group. Both treated groups received dexamethasone intravenously for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the last day of treatment). The control groups received no steroid treatment. A significantly lower absolute cell count and percentage of neutrophils (PMN) in the TAF and significantly higher dynamic lung compliance (Cdyn) values were observed in both the MED treated compared to the untreated infants and the ED treated infants compared to the control group. Moreover these changes were more precocious in the ED Group compared to the MED Group. Our study suggests that dexamethasone could be more efficacious in reducing effects of ventilator-induced lung injury in preterm infants at high risk of CLD when started earlier.\n Copyright 2004 S. Karger AG, Basel", "In a multicenter trial of steroid therapy for chronic neonatal oxygen dependence, 287 neonates were randomly allocated from around 3 weeks of age, to dexamethasone or placebo. Active treatment significantly reduced the duration of further assisted ventilation among infants who were ventilator dependent at entry (median days for survivors, 11 vs 17.5). There were no statistically significant differences between the total groups of survivors in time receiving supplemental oxygen and length of stay in hospital, although the trend favored the dexamethasone group. Twenty-five infants in each group died prior to hospital discharge; most were ventilator dependent at trial entry. Open treatment with steroids was later given to 18% in the active group and to 43% in the placebo group. There was no evidence of serious side effects; in particular, infection rates were similar in the two groups.", "A randomized trial was conducted of dexamethasone therapy in infants with bronchopulmonary dysplasia who were dependent on respirators and were not progressing clinically despite conventional treatment. Babies were admitted to the study if they had a roentgenogram and clinical diagnosis of bronchopulmonary dysplasia, were 2 to 6 weeks in age, weighed less than 1,500 g, had made no progress in weaning for the preceding five days, and were free of sepsis, patent ductus arteriosus, and congenital heart disease, and had had no intravenous fat for at least 24 hours. After parental consent was obtained, infants were randomly assigned to control or treatment groups. The study hypothesis was that with steroid treatment, babies could be weaned from the respirator within 72 hours and would show a significant improvement in lung compliance within that time. Sequential analysis exceeded criterion (P less than .05) when seven consecutive untied pairs showed weaning with dexamethasone and failure to wean in control infants. Pulmonary compliance improved by 64% in the treated group and 5% in the control group (P less than .01). No significant intergroup differences were noted in mortality, length of hospital stay, sepsis, hypertension, hyperglycemia, or electrolyte abnormalities. Study design permits the conclusion that dexamethasone can produce substantial short-term improvement in lung function, often permitting rapid weaning from the respirator, but long-term efficacy and safety must be demonstrated by further investigations.", "This randomized controlled trial was designed to answer the question: does administration of dexamethasone to neonates with bronchopulmonary dysplasia decrease the need for assisted ventilation? Twenty-five infants with a birth weight < 1501 g, requiring mechanical ventilation and FiO2 of > or = 0.30 at 21-35 days of age, were randomized to treatment with iv dexamethasone or to sham injections for 12 days. The primary outcome criterion was extubation within seven days after study entry. Treatment (n = 12) and control (n = 13) groups were well matched at entry. Dexamethasone facilitated weaning from assisted ventilation (p = 0.0154). There was no increased incidence of infection. Dexamethasone treatment resulted in a significant increase in glucosuria (p = 0.0002) and in systolic blood pressure (p = 0.0034). There was a significant decrease in heart rate (p = 0.0001) and a significant weight loss (p = 0.0002) following dexamethasone treatment. Dexamethasone treatment facilitated weaning from assisted ventilation but several systemic effects were noted that deserve further evaluation before dexamethasone becomes routine treatment.", "To assess the effect on duration of ventilator dependency of a 42-day tapering course of dexamethasone in very low birth weight neonates.\n Infants (N = 118) were assigned randomly, within birth weight/gender strata, to treatment with either a 42-day tapering course of dexamethasone or an equal volume of saline as placebo. Entry criteria were 1) birth weight <1501 g; 2) age between 15 and 25 days; 3) <10% decrease in ventilator settings for 24 hours and FIO2 >/=0.3; 4) absence of patent ductus arteriosus, sepsis, major congenital malformation, congenital heart disease; and 5) no evidence of maternal HIV or hepatitis B infection. The dosage schedule was 0.25 mg/kg bid for 3 days, then 0.15 mg/kg bid for 3 days, then a 10% reduction in the dose every 3 days until a dose of 0.1 mg/kg had been given for 3 days, from which time a dose of 0.1 mg/kg qod was continued until 42 days after entry. The primary endpoint was the number of days on assisted ventilation after study entry. Secondary outcomes of interest included days on supplemental oxygen, days of hospitalization, and potential adverse effects, such as infection, gastrointestinal bleeding, left ventricular hypertrophy, and severe retinopathy of prematurity.\n Infants in the dexamethasone- and placebo-treated groups were similar in terms of baseline attributes, including birth weight, gestational age, gender, race, and ventilator settings at entry. Infants treated with dexamethasone were on assisted ventilation and supplemental oxygen for fewer days after study entry (median days on ventilator, 5th and 95th percentiles, 13 [1-64] vs 25 [6-104]; days on oxygen, 59 [6-247] vs 100 [11-346]). No differences were found in risk of death, infection, or severe retinopathy. In subgroup analyses, the association of dexamethasone with more rapid weaning from the ventilator was weaker among infants enrolled before the 16th day of life, infants with chest radiographs showing cystic changes and/or hyperinflation, and infants requiring an FIO2 >/=0.7 or a peak inspiratory pressure >/=19 at study entry.\n A 42-day tapering course of dexamethasone decreases the duration of ventilator and oxygen dependency in very low birth weight infants and is not associated with an increased risk of short-term adverse effects.", "Eighteen infants were entered into a randomized, placebo-controlled trial of dexamethasone therapy for chronic lung disease. Initial ventilation requirements were similar in the two groups, although all infants were in headbox oxygen on entry to the trial. The dexamethasone-treated infants showed a significantly more rapid improvement during the 1st week of treatment, although the overall duration of oxygen therapy was similar in both groups. Cranial ultrasound examination revealed new periventricular abnormalities in three out of the five dexamethasone-treated infants who had previously normal scans, compared with none of four similar placebo-treated infants. A large trial, focussing on potential complications, is now needed.", "To determine whether dexamethasone therapy altered the outcome of chronic lung disease in neonates, we conducted a prospective, randomized, placebo-controlled trial. Twenty-one 30-day-old oxygen- and ventilator-dependent infants were enrolled. The mean (+/- SD) birth weight was 808.1 +/- 141 gm and the mean gestational age was 26.0 +/- 1.5 weeks. There were 17 black and 12 male infants. Twelve received placebo and nine received dexamethasone. Neither severity of early illness, birth weight, gestational age, age when treated, gender and race distribution, nor frequency of diuretic therapy differed significantly between groups. The age at extubation, 57.2 days (placebo) versus 39.4 days (steroid), was significantly different. The average oxygen requirements of the steroid-treated patients was significantly lower than for placebo-treated patients during the first 10 days of treatment. There were no differences for placebo-versus steroid-treated patients in age when weaned to room air (95.5 days vs 74.9 days), age at discharge (119 days vs 111 days), or number of deaths (2 (17%) vs 1 (11%]. Dexamethasone therapy was associated with a significantly increased incidence of hyperglycemia (89% vs 8%) but did not influence the incidence of hypertension, intracranial hemorrhage, infection, or retinopathy of prematurity. The steroid-treated patients had a significant delay in weight gain during the first 3 weeks of treatment but recovered by discharge. Our results suggest that dexamethasone produces acute improvement in infants with lung disease but no long-term effect on mortality rate, duration of oxygen requirement or age at discharge.", "A short course of moderately early dexamethasone therapy with a starting dose of 0.5 mg/kg/day improves lung compliance and shortens the duration of ventilatory support in preterm infants with respiratory distress syndrome (RDS). We conducted a double-blind, randomized study to evaluate whether a moderately early 14-day weaning course of low-dose dexamethasone affects adrenal function and facilitates weaning from the ventilator.\n Thirty-six preterm infants with a gestational age < or =32 weeks who required ventilatory support for RDS on days 7-14 were randomized to a 14-day treatment course with dexamethasone (0.2 mg/kg/day start, tapering doses) or placebo (equivalent amounts of normal saline). Prior to the first study treatment and the day after completion of the treatment course, adrenal function was assessed from serum cortisol levels drawn before and 30 min after intravenous administration of 0.1 mg Cortrosyn. Extubation rate during treatment in both groups was compared.\n In both groups baseline serum cortisol levels decreased significantly during treatment, but stimulated cortisol levels did not change. After the 14-day treatment course, stimulated cortisol levels increased significantly from baseline levels in both groups (p<0.001), following Cortrosyn administration. More infants in the dexamethasone group were extubated within 7-14 days of study entry than in the placebo group (p<0.05). Hyperglycemia was more frequently diagnosed in the dexamethasone group and open-label dexamethasone treatment was given more frequently in the control group.\n A moderately early 14-day weaning course of low-dose dexamethasone does not significantly suppress the adrenal function of very preterm infants with RDS, but accelerates weaning from the ventilator." ]

[ "9078829", "9425384", "9972083", "7658266" ]

[ "Efficacy and acceptability of different modes of oxygen administration in children: implications for a community hospital.", "Oxygen administration to hypoxic children in Ethiopia: a randomized controlled study comparing complications in the use of nasal prongs with nasopharyngeal catheters.", "Comparison of nasal prongs with nasal catheters in the delivery of oxygen to children with hypoxia.", "Comparison of nasal prongs and nasopharyngeal catheter for the delivery of oxygen in children with hypoxemia because of a lower respiratory tract infection." ]

[ "Eighty under-five children admitted in the pediatric ward with acute respiratory distress requiring oxygen inhalation were prospectively studied. Oxygen was administered to all the children by head box, face mask, nasopharyngeal catheter, and twin-holed prenasal catheter in a predetermined sequence. Oxygen was delivered at a flow rate of 4 l/min in the head box and by face mask and at a rate of 1 l/min for nasopharyngeal catheter and twin-holed prenasal catheter. There was a significant rise in paO2 and SaO2 values with all the oxygen delivery methods. The number of children who achieved paO2 of > 90 mmHg with oxygen delivered by head box was 53 (69 per cent), with face mask 37 (57 per cent), with nasopharyngeal catheter 13 (26 per cent), and with twin-holed prenasal catheter 18 (25 per cent). In view of high acceptability of twin-holed prenasal catheter, a further pilot study involving 10 children was carried out to compare the efficacy of head box and twin-holed prenasal catheter at an identical oxygen flow rate of 4 l/min. The number of children achieving paO2 of > 90 mmHg were comparable, i.e. seven (70 per cent) and eight (80 per cent) when the oxygen was delivered by head box and twin-holed prenasal catheter, respectively. It is concluded that both head box and twin-holed prenasal catheter are equally effective, acceptable and safe methods for administration of oxygen to children with acute respiratory disorders. In view of the cost-effectiveness, and easy availability and affordability of twin-holed prenasal catheter, it should be popularized in the small hospitals in the community, while head box should be reserved for use in the referral hospitals.", "Oxygen administration is one of the most important therapeutic interventions for a child with severe acute lower respiratory tract infection (ALRI). Inexpensive and efficient methods of oxygen administration are highly desirable in hospitals in developing countries. The objectives of this study were to compare the frequency and nature of complications when nasopharyngeal catheters or nasal prongs are used to deliver oxygen. One hundred and twenty-one children between the ages of 2 weeks and 5 years with hypoxia due to ALRI were randomized to receive oxygen via a catheter (61 children) or via nasal prongs (60 children). The two groups were similar in terms of diagnoses, clinical severity, oxygen saturation on admission and case fatality rates. There was no difference in the incidence of hypoxaemic episodes between the two groups. The oxygen flow rates required on the day of admission for adequate oxygenation (SaO2 > 90%) ranged from 0.8 litres per minute to 1.2 litres per minute. The required oxygen flow rate decreased during the course of treatment. Mucus production was more of a problem in the catheter group, and nasal blockage, intolerance of the method of oxygen administration and nursing effort were generally higher amongst the catheter group, but none of these differences was significant. Ulceration or bleeding of the nose was significantly more common in the catheter group (19.7% vs 6.7%, p < 0.05). Abdominal distension and nasal perforation were not seen in either group. This study suggests that nasal prongs are safer, more comfortable and require less nursing expertise than nasopharyngeal catheters for administration of oxygen to children.", "Efficient, inexpensive, and safe methods of oxygen delivery are needed for children with severe pneumonia in developing countries. The objective of this study was to estimate the frequency of complications when nasal catheters or nasal prongs are used to delivery oxygen. Ninety-nine children between 2 weeks and 5 years of age with hypoxia were randomized to receive oxygen via nasal catheter (49 children) or nasal prongs (50 children). There was no difference in the incidence of hypoxaemic episodes or in the oxygen flow rates between the two groups. Mucus production was more of a problem in the catheter group. Nasal blockage, intolerance to the method of administration, and nursing effort were generally higher amongst the catheter group, but these differences were not significant, except for nursing effort, when all age groups were analysed together.", "To determine the best method of oxygen delivery for children in developing countries who have hypoxemia caused by acute lower respiratory tract infection.\n One hundred eighteen children between 7 days and 5 years of age with a lower respiratory tract infection and arterial hemoglobin oxygen saturation (Sao2) less than 90% were randomly selected to receive oxygen by nasopharyngeal (NP) catheter (n = 56) or nasal prongs (n = 62). A crossover study to determine the flow rate necessary to achieve an Sao2 of 95% was performed in 60 children.\n One hundred twelve children could be oxygenated by the allocated method; in six oxygenation was poor with either method. The mean duration of therapy was 87.5 hours for the prongs and 94.9 hours for the NP catheter (not significant). The median oxygen consumption was 2142 L for prongs and 1692 L for the NP catheter (not significant). In the crossover study the prongs needed, on average, 26% higher oxygen flow rates than the NP catheter to obtain an Sao2 of 95% (p = 0.003). Complete nasal obstruction was observed in 24 of the children (44%) in the NP catheter group and in 8 (13%) in the prongs group (p < 0.001). Eighteen children died, 11 with NP catheter and 7 with prongs (not significant).\n Because nasal prongs are less prone to complications, and oxygenation in children is equally effective, they are a more appropriate method than the NP catheter for oxygen delivery to children in developing countries with acute lower respiratory tract infections." ]

[ "10982571", "617630", "9224191", "3712426", "15204821", "3485760", "9363516" ]

[ "Can anti-smoking television advertising affect smoking behaviour? controlled trial of the Health Education Authority for England's anti-smoking TV campaign.", "Reducing the risk of cardiovascular disease: effects of a community-based campaign on knowledge and behavior.", "The effectiveness of a media-led intervention to reduce smoking among Vietnamese-American men.", "Tailored media can enhance the success of smoking cessation clinics.", "Media and community campaign effects on adult tobacco use in Texas.", "Evaluation of the Sydney \"Quit. For Life\" anti-smoking campaign. Part 2. Changes in smoking prevalence.", "Twelve-year results of the Coronary Risk Factor Study (CORIS)." ]

[ "To evaluate the effectiveness of the Health Education Authority for England's anti-smoking television advertising campaign in motivating smokers to give up and preventing relapse in those who had already given up.\n A prospective, controlled trial was conducted in four TV regions in central and northern England. One region received no intervention (controls), two regions received TV anti-smoking advertising (TV media), and one region received TV anti-smoking advertising plus locally organised anti-tobacco campaigning (TV media + LTCN). The TV advertisements were screened in two phases over 18 months; during the first phase the intensity of the advertising was varied between TV regions. 5468 men and women (2997 smokers, 2471 ex-smokers) were selected by two stage random sampling and interviewed before the intervention, of whom 3610 were re-interviewed six months later, after the first phase of the campaign. Only those interviewed at six months were followed to the main end point at 18 months when 2381 subjects were re-interviewed.\n Self reports of cigarette smoking at the 18 month follow up were compared between the three levels of intervention. Odds ratios for intervention effects were adjusted for pre-intervention predictors of outcome and pooled for smokers and ex-smokers using meta-analytic methods.\n After 18 months, 9. 8% of successfully re-interviewed smokers had stopped and 4.3% of ex-smokers had relapsed. The pooled adjusted odds ratio for not smoking in the TV media only condition compared to controls was 1.53 (95% confidence intervals (CI) 1.02 to 2.29, p = 0.04), and for TV media + LTCN versus controls, 1.67 (95% CI 1.0 to 2.8, p = 0.05). There was no evidence of an extra effect of the local tobacco control network when combined with TV media (odds ratio 1.15, 95% CI 0.74 to 1.78, p = 0.55). The was also no evidence of any intervention effects after the first phase of the TV media campaign, including no effect of varying the intensity of the advertising during this initial phase. Applying these results to a typical population where 28% smoke and 28% are ex-smokers, and where there would be an equal number of quitters and relapsers over an 18 month period without the campaign, suggests that the campaign would reduce smoking prevalence by about 1.2%.\n The Health Education Authority for England's anti-smoking TV campaign was effective in reducing smoking prevalence through encouraging smokers to stop and helping prevent relapse in those who had already stopped. The lack of an effect after the first phase of the campaign indicates that if advertising at this intensity is to have an impact, a prolonged campaign is necessary. These results support the UK governments' recent decision to fund similar campaigns, and suggests that anti-smoking TV advertising should be undertaken routinely as an essential component of any population smoking reduction strategy. Reducing smoking prevalence would make a substantial contribution to achieving the UK government's target of preventing 300 000 cancer and heart disease deaths over the next 10 years.", "In 1972 the Stanford Heart Disease Prevention Program launched a three-community field study. A multimedia campaign was conducted for two years in two California communities (Watsonville and Gilroy), in one of which (Watsonville) it was supplemented by an intensive-instruction program with high-risk subjects. A third community (Tracy) was used as a control. The campaigns were designed to increase participants' knowledge of the risk factors for cardiovascular disease, to change such risk-producing behavior as cigarette smoking, and to decrease the participants' dietary intake of calories, salt, sugar, saturated fat, and cholesterol. Results of a sample survey indicate that substantial gains in knowledge, in behavioral modification, and in the estimated risk of cardiovascular disease can be produced by both methods of intervention. The intensive-instruction program, when combined with the mass-medica campaign, emerged as the most effective for those participants who were initially evaluated to be at high risk. The results after two years of intervention are reported for effects on knowledge and behavioral change for the total participant samples and for the high-risk subsamples in each of the three communities.", "This study evaluated an anti-tobacco campaign targeting Vietnamese men in San Francisco, Calif.\n The intervention included Vietnamese-language media, health education materials, and activities targeting physicians, youth, and businesses. Evaluation involved pretest and posttest cross-sectional telephone surveys and multiple logistic regression analyses designed to identify variables associated with smoking and quitting.\n At posttest, the odds of being a smoker were significantly lower (odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.68, 0.99), and the odds of being a quitter were significantly higher (OR = 1.65, 95% CI = 1.27, 2.15), in San Francisco than in a comparison community.\n Despite modest success, further efforts are needed to reduce smoking among Vietnamese-American men.", "Smokers recruited through the medical outpatient clinics of two similar Veterans Hospitals over two successive years participated in a smoking cessation study which randomized them between a group assigned to behavior modification clinics and a group receiving a packet of smoking cessation material in the mail. Following the second year's clinics at the site of one of the two hospitals, an intensive media campaign, based on the content of the behavior modification program, was targeted at the study population over commercial television and radio. The six-month abstinence rate for clinic participants measured by self-report, serum thiocyanate and exhaled air carbon monoxide was 36.8% in the group assigned to clinic followed by media, 20.2% in the group assigned to clinic alone, and 10.6% in the group receiving materials in the mail. The difference in cessation rates between the clinic participants who were and those who were not exposed to the media following their clinics was significant at the 0.05 significance level (chi 2 = 3.9, 1 d.f.). Logistic analysis confirmed the benefit of the media campaign.", "The present study reports on the effects on adult tobacco cessation of a comprehensive tobacco-use prevention and cessation program in the state of Texas. Differences in cessation rates across treatment conditions were measured by following a panel of 622 daily smokers, recruited from the original cross-sectional sample, from baseline to follow-up. The adult media campaign combined television, radio, newspaper and billboard advertisements featuring messages and outreach programs to help adults avoid or quit using tobacco products. The ads also promoted quitting assistance programs from the American Cancer Society Smokers' Quitline, a telephone counseling service. The cessation component of the intervention focused on increasing availability of and access to cessation counseling services and pharmacological therapy to reduce nicotine dependence. Both clinical and community-based cessation programs were offered. Treatment areas which combined cessation activities with high level media campaigns had a rate of smoking reduction that almost tripled rates in areas which received no services, and almost doubled rates in areas with media campaigns alone. Analyses of the dose of exposure to media messages about smoking cessation show greater exposure to television and radio messages in the areas where high level media was combined with community cessation activities than in the other areas. Results also show that exposure to media messages was related to processes of change in smoking cessation and that those processes were related to the quitting that was observed in the group receiving the most intensive campaigns.", "Between June and November 1983, the \"Quit. For Life\" media campaign was conducted in Sydney to reduce the prevalence of smoking. Surveys on a cross-sectional sample of the Sydney population were conducted before and after the campaign, and similar measures were undertaken in the rest of Australia for comparison. The sample sizes for both the Sydney and control areas comprised more than 4000 subjects. In addition, a cohort of 949 residents of Sydney and Melbourne were followed for changes in the prevalence of smoking during the year of the campaign. The cross-sectional survey results for 1984 and 1983 demonstrated decreases in the prevalence of smoking of approximately 1% for both men and women in Sydney compared with the rest of Australia. In the cohort study there was a 3.4% decrease in smoking prevalence in Sydney compared with a 0.8% increase in Melbourne. The pooled estimate of the difference in smoking prevalence attributable to the campaign was 2.8% (95% confidence interval, 0.5%-5.1%).", "After 4 years a coronary heart disease risk factor intervention programme produced equally large and significantly reduced risk profiles in two intervention towns compared with a control town. Intervention effects through community participation were assessed after cessation of the active intervention programme. The impact of secular trends was assessed in the control town and in two previously unstudied towns.\n Cross-sectional surveys were done in a random sample of 1620 participants aged 15-64 years in the three original towns 12 years after the initial quasi-experimental study. Two years later 327 subjects, aged 35-44 years, were studied in the original control town and in two non-intervention towns. Risk factor knowledge, smoking and medical histories were determined by questionnaire. Blood pressure, anthropometry and blood lipids were recorded. Data were compared across towns, and with previous surveys.\n At 12 years the low intensity intervention town maintained a significantly better risk factor profile than the control town, while the high intensity intervention town now matched the control town. No differences in risk factor profiles were found between the control town and the two new towns. Deaths from coronary heart disease and strokes showed a downward trend in the study area.\n Outcome suggests large ongoing secular trends during the study could have overtaken the intervention effects in the high intensity town, but not in the low intensity intervention town, which showed an advantage over the control town. These results support the effectiveness of media-based, long term health promotion strategies to reduce cardiovascular disease risk profiles." ]

[ "18073360" ]

[ "Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial." ]

[ "Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit (ICU) patients, but this and other benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and coma, associated with prolonged hospital stays, costs, and increased mortality. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction.\n To determine whether dexmedetomidine reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam.\n Double-blind, randomized controlled trial of 106 adult mechanically ventilated medical and surgical ICU patients at 2 tertiary care centers between August 2004 and April 2006. Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours. Study drugs were titrated to achieve the desired level of sedation, measured using the Richmond Agitation-Sedation Scale (RASS). Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU).\n Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal.\n Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0; P = .01) and a lower prevalence of coma (63% vs 92%; P < .001) than sedation with lorazepam. Patients sedated with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%; P = .04). The 28-day mortality in the dexmedetomidine group was 17% vs 27% in the lorazepam group (P = .18) and cost of care was similar between groups. More patients in the dexmedetomidine group (42% vs 31%; P = .61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group (P = .48).\n In mechanically ventilated ICU patients managed with individualized targeted sedation, use of a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion.\n clinicaltrials.gov Identifier: NCT00095251." ]

[ "11054200", "1536481", "10844490", "8329794" ]

[ "Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists.", "Histamine antagonists in the treatment of acute allergic reactions.", "Famotidine in the treatment of acute urticaria.", "Oral agents in the management of urticaria: patient perception of effectiveness and level of satisfaction with treatment." ]

[ "Although the addition of H(2) blockers to H(1) antagonists has been promoted for use in anaphylaxis, there have been no large studies establishing the advantage of this approach in treating acute allergic syndromes. In this study we tested the hypothesis that combined H(1) and H(2) blockage results in improved outcomes in patients treated for acute allergic syndromes compared with treatment with H(1) blockade alone.\n In a randomized, double-blind, placebo-controlled trial, 91 adult patients with acute allergic syndromes were treated with either 50 mg of diphenhydramine and saline solution (control group) or with 50 mg of diphenhydramine and 50 mg of ranitidine (active group). These patients were treated with parenteral administration. Patients were recruited from an emergency department at an urban academic medical center. The primary endpoints were resolution of urticaria, angioedema, or erythema at 2 hours after protocol treatment. Areas of cutaneous involvement, heart rates, blood pressures, respiratory findings, and symptom scores were also assessed at baseline, 1 hour, and 2 hours.\n There were significantly more patients without urticaria at 2 hours among the patients in the active group compared with those in the control group. Both groups had similar proportions of urticaria at baseline. Logistic regression models to predict resolution of urticaria, which accounted for baseline urticarial involvement, showed odds ratios in favor of the active group treatment. Similar findings were observed when the absence of both urticaria and angioedema was considered as the dependent variable. There was not a significant difference between the 2 groups with regard to the absence of erythema or angioedema (irrespective of the presence of urticaria) at 2 hours. Blood pressure and symptoms did not show differences between the 2 groups over time. Lower heart rates were observed 1 hour after treatment in the active treatment group (mean reduction 10 beats/min) compared with those found in the placebo group (mean reduction 6 beats/min).\n These data show that adding H(2) blockers to H(1) antagonists results in additional improvement of certain cutaneous outcomes for patients presenting with acute allergic syndromes. These findings favor the recommendation for using combined H(1) and H(2) antihistamines in acute allergic syndromes.", "We compared the efficacies of cimetidine (an H2-receptor antagonist) and diphenhydramine (an H1-receptor antagonist) alone and in combination for alleviation of symptoms of acute allergic reactions. STUDY DESIGN AND INTERVENTIONS: In this prospective, randomized, double-blind study, patients and examiners assessed the severity of symptoms and signs of acute allergic reactions using a visual-analog scale before treatment and 30 minutes after treatment with 300 mg IV cimetidine and placebo, 50 mg IV diphenhydramine and placebo, or diphenhydramine plus cimetidine.\n Thirty-nine patients with acute allergic reactions presenting to two emergency departments of teaching hospitals.\n Of the 35 patients with pruritus, all 12 receiving diphenhydramine placebo had clinically significant relief compared with six of ten (60%) receiving cimetidine plus placebo (P = .03). Twelve of 13 (92%) receiving diphenhydramine plus cimetidine had relief, which was not a significant difference from the single drugs. Comparison of mean differences in pretreatment and post-treatment symptom scores (relief scores) among groups of patients with pruritus detected significantly more relief in the group receiving diphenhydramine plus placebo (80.3 +/- 7.4) than in those receiving cimetidine plus placebo (48.8 +/- 13.4) (P = .022). Of the 33 patients with urticaria, five of 11 (46%) receiving diphenhydramine plus placebo had clinically significant relief compared with eight of ten (80%) receiving cimetidine plus placebo (P = .18). Eleven of 12 patients (92%) receiving diphenhydramine plus cimetidine had relief, which is a significant difference from those receiving diphenhydramine plus placebo (P = .027). Comparison of mean relief scores in patients with urticaria detected significantly more relief in the group receiving diphenhydramine plus cimetidine (55.3 +/- 6.5) than in the group receiving diphenhydramine plus placebo (30.7 +/- 6.1) (P = .006).\n For treatment of pruritus from acute allergic reactions, diphenhydramine is more effective than cimetidine, and the combination offers no additional benefit. For treatment of acute urticaria, the combination of cimetidine and diphenhydramine is more effective than diphenhydramine alone.", "Recent studies suggest that histamine H2-receptor antagonists may be useful in the treatment of urticaria. This study was conducted to determine whether famotidine, a H2 antagonist, is effective in the treatment of acute urticaria and compare its effect with that of the H1 antagonist diphenhydramine. In this prospective, double-blind, controlled trial, 25 patients with urticaria of less than 72 h duration were randomized to receive a single dose of either famotidine 20 mg i.m. or diphenhydramine 50 mg i.m. Prior to treatment and 30 min after treatment, patients rated pruritus and sedation using visual analogue scales, while physicians evaluated intensity of urticaria and percentage of body surface area involved by urticaria. Famotidine was found to reduce pruritus associated with acute urticaria, intensity of urticaria, and body surface area affected by urticaria without causing sedation. Famotidine was comparable to diphenhydramine in efficacy; however, there was a (nonsignificant) trend for diphenhydramine to be more effective than famotidine in the treatment of pruritus, and for famotidine to be more effective in the reduction of surface area of involvement. It is concluded that famotidine merits further investigation as a potential medication for treatment of urticaria.", "Orally administered diphenhydramine, famotidine, and cromolyn sodium were compared for their abilities to alleviate symptoms of acute urticaria.\n This was a prospective, randomized, blind study, implemented in the emergency departments (EDs) of two teaching hospitals, each with an annual average of 40,000 ED patient visits. Patient perception of the effectiveness of treatment was assessed using a visual analog scale.\n 33 adult patients presenting to the EDs were entered into the study over a one-year period. Of these, 8 were lost to follow-up and 5 were noncompliant with medications and not included in data analysis. Twenty adult patients, aged 19-78 years, completed the five-day study: 7 received diphenhydramine, 6 received famotidine, and 7 received cromolyn sodium.\n Patients receiving diphenhydramine reported the greatest satisfaction with treatment: 86 percent (6/7) indicated they would use the medication again. Fifty percent (3/6) in the famotidine group and 43 percent (3/7) in the cromolyn sodium group rated the treatment as worth using again. Patients receiving famotidine reported the greatest occurrence of adverse effects (50 percent, 3/6); the lowest incidence of such effects was seen in the cromolyn sodium group (14 percent, 1/7). Patients receiving diphenhydramine reported adverse effects at a rate of 43 percent (3/7).\n Our results suggest that patients receiving diphenhydramine are more satisfied with their treatment than are patients receiving famotidine or cromolyn sodium." ]

[ "7010875" ]

[ "Anti-depressive treatment in Parkinson's disease. A controlled trial of the effect of nortriptyline in patients with Parkinson's disease treated with L-DOPA." ]

[ "Nineteen patients with L-DOPA treated parkinsonism involving depressive symptoms, the therapeutic effect of nortriptyline was compared to placebo in a controlled trial. The depressive and neurological symptoms were evaluated by rating scales. Nortriptyline had a clinical significant effect with regard to the depressive symptoms, whereas the neurological parameters were unchanged. The authors suggest the depression in Parkinson's disease to be of both reactive and endogenous origins." ]

[ "17504683", "9295239", "12809582", "17065029", "9875583", "9189212", "11216930", "9233868", "10732934", "17945069", "11694842", "8101302" ]

[ "[Randomized clinical trial investigating three chemoprophylaxis regimens for latent tuberculosis infection in HIV-infected patients].", "A trial of three regimens to prevent tuberculosis in Ugandan adults infected with the human immunodeficiency virus. Uganda-Case Western Reserve University Research Collaboration.", "[Randomized trial of three regimens to prevent tuberculosis in HIV-infected patients with anergy].", "Effect of tuberculosis preventive therapy on HIV disease progression and survival in HIV-infected adults.", "Twice weekly tuberculosis preventive therapy in HIV infection in Zambia.", "Isoniazid preventive therapy for tuberculosis in HIV-1-infected adults: results of a randomized controlled trial.", "Long-term effect of preventive therapy for tuberculosis in a cohort of HIV-infected Zambian adults.", "A controlled trial of isoniazid in persons with anergy and human immunodeficiency virus infection who are at high risk for tuberculosis. Terry Beirn Community Programs for Clinical Research on AIDS.", "Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group.", "Randomised controlled trial of isoniazid preventive therapy in South African adults with advanced HIV disease.", "No effect of isoniazid prophylaxis for purified protein derivative-negative HIV-infected adults living in a country with endemic tuberculosis: results of a randomized trial.", "Effect of isoniazid prophylaxis on incidence of active tuberculosis and progression of HIV infection." ]

[ "To evaluate the adherence to, and safety of three chemoprophylaxis regimens for latent tuberculosis (TB) infection in HIV-infected patients with a positive tuberculin skin test.\n A randomized, comparative, open clinical assay was carried out in 316 HIV-infected patients in 12 Spanish hospitals. Patients were randomly assigned to one of three regimens, 108 to isoniazid for six months (6H), 103 to rifampin and isoniazid for three months (3RH), and 105 to rifampin and pyrazinamide for two months (2RZ). After completion of treatment, patients were followed-up for two years.\n The period of observation following completion of treatment was 115, 108 and 101 person-years for 6H, 3RH and 2RZ, respectively. Twenty-seven percent of patients voluntarily abandoned chemoprophylaxis and 9.7% were withdrawn due to adverse side-effects or interactions. Seven patients were withdrawn due to hepatotoxicity (5 in 6H, 2 in 3RH and 0 in 2RZ). No appreciable differences were found among the three regimens. There were 11 cases of tuberculosis during follow-up. The TB rates (cases per 100 person-years) in the three treatment groups were 3.48 in 6H, 4.63 in 3RH and 1.98 in 2RZ. With respect to 2RZ, the relative risk for TB in the 6H and 3RH regimens was 1.76 and 2.34, respectively.\n The safety of the 2RZ regimen for prophylaxis of latent TB infection in HIV patients was similar to that of the 6H and 3RH regimens. The incidence of hepatotoxicity was not higher in patients who received 2RZ.", "Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common.\n We performed a randomized, placebo-controlled trial in 2736 HIV-infected adults recruited in Kampala, Uganda. Subjects with positive tuberculin skin tests (induration, > or =5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462). Subjects with anergy (0 mm induration in reaction to PPD and candida antigens) were randomly assigned to receive either placebo (323 subjects) or six months of isoniazid (395). The medications were dispensed monthly and were self-administered.\n Among the PPD-positive subjects, the incidence of tuberculosis in the three groups that received preventive therapy was lower than the rate in the placebo group (P=0.002 by the log-rank test). The relative risk of tuberculosis with isoniazid alone, as compared with placebo, was 0.33 (95 percent confidence interval, 0.14 to 0.77); with isoniazid and rifampin, 0.40 (0.18 to 0.86); and with isoniazid, rifampin, and pyrazinamide, 0.51 (0.24 to 1.08). Among the subjects with anergy, the relative risk of tuberculosis was 0.83 (95 percent confidence interval, 0.34 to 2.04) with isoniazid as compared with placebo. Side effects were more common with the multidrug regimens, and particularly with the regimen containing pyrazinamide. Survival did not differ among the groups, but the subjects with anergy had a higher mortality rate than the PPD-positive subjects.\n A six-month course of isoniazid confers short-term protection against tuberculosis among PPD-positive, HIV-infected adults. Multidrug regimens with isoniazid and rifampin taken for three months also reduce the risk of tuberculosis.", "To evaluate the efficacy of three regimens of prophylactic therapy for tuberculosis in HIV-infected patients with anergy.\n Prospective, multi-center, randomized, comparative, and open clinical trial. Anergy was defined as absence of induration in response to three antigens (PPD, Candida albicans and parotiditis antigen) applied by the Mantoux method. Patients were randomized into one of the following prophylactic treatment groups: isoniazid for six months (6H), rifampin plus isoniazid for three months (3RH), rifampin plus pyrazinamide for two months (2RZ) or no treatment (NT). After completion of treatment, patients were followed up for two years.\n A total of 319 patients were included in the study, 83 in the 6H regimen, 82 in 3RH, 77 in 2RZ and 77 in NT. The observation period following treatment was 88, 96, 81 and 126 person-years, respectively, for 6H, 3RH, 2RZ and NT. There were 11 cases of tuberculosis during the follow-up period. The tuberculosis rates (cases per 100 person-years) were 3.4, 3.1, 1.2 and 3.1 for 6H, 3RH, 2RZ and NT respectively, with relative risks in regimens 6H, 3RH and 2RZ with respect to NT of 1.07 (0.24-4.80), 0.98 (0.22-4.4) and 0.39 (0.04-3.48), all statistically non-significant. Twenty-nine patients died during the follow-up period, none due to tuberculosis, and no appreciable differences were found among the groups.\n The results showed no significant decrease in the risk of developing tuberculosis with any of the evaluated regimens and, therefore, do not support the use of antituberculosis chemoprophylaxis in anergic HIV-infected patients.", "To determine whether tuberculosis (TB) preventive therapies alter the rate of disease progression to AIDS or death and to identify significant prognostic factors for HIV disease progression to AIDS.\n In a randomized placebo-controlled trial in Kampala, Uganda, 2,736 purified protein derivative (PPD)-positive and anergic HIV-infected adults were randomly assigned to four and two regimens, respectively. PPD-positive patients were treated with isoniazid (INH) for 6 months (6H; n = 536), INH plus rifampicin for 3 months (3HR; n = 556), INH plus rifampicin plus pyrazinamide for 3 months (3HRZ; n = 462), or placebo for 6 months (n = 464). Anergic participants were treated with 6H (n = 395) or placebo (n = 323).\n During follow-up, 404 cases progressed to AIDS and 577 deaths occurred. The cumulative incidence of the AIDS progression was greater in the anergic cohort compared to the PPD-positive cohort (p < .0001). Among PPD-positive patients, the relative risk of the AIDS progression with INH alone was 0.95 (95% CI 0.68-1.32); with 3HR it was 0.83 (95% CI 0.59-1.17); and with 3HRZ it was 0.76 (95% CI 0.52-1.08), controlling for significant baseline predictors. Among anergic patients, the relative risk of the AIDS progression was 0.81 (95% CI 0.56-1.15). Survival was greater in the PPD-positive cohort compared to the anergic cohort (p = .0001).\n The number of signs or symptoms at baseline and anergic status are associated with increasing morbidity and mortality. Even though the tuberculosis preventive therapies were effective in reducing the incidence of TB for HIV-infected adults, their benefit of delaying HIV disease progression to AIDS was not observed.", "A randomized double-blind placebo-controlled trial was conducted to estimate the efficacy of preventive therapy for tuberculosis (TB) in HIV-infected adults in Lusaka, Zambia. The main outcome measures were the incidence of TB, mortality and adverse drug reactions.\n During a 2 year period, 1053 HIV-positive individuals without evidence of clinical TB were randomly assigned to receive 6 months of isoniazid twice a week (H), or 3 months of rifampicin twice a week (R) plus pyrazinamide (Z), or a placebo. Therapy was taken twice a week and was self administered. Subjects presenting with symptoms during the follow-up period were investigated for TB.\n The 1053 subjects in the study were followed up for a total of 1631 person-years (median = 1.8 years). Twenty-nine subjects were taken off treatment as a result of adverse drug reactions. A total of 96 cases of TB/probable TB (59 TB and 37 probable TB) were diagnosed during the study period and 185 deaths were reported. One hundred and fifteen subjects (11%) did not return to the study clinic at any time after enrolment. The incidence of TB was lower in those subjects on preventive therapy (H and RZ groups combined) compared with those on placebo (rate ratio = 0.60, 95% CI: 0.36-1.01, P = 0.057), as was the incidence of TB/probable TB (rate ratio = 0.60, 95% CI: 0.40-0.89, P = 0.013). The effect of preventive therapy was greater in those with a tuberculin skin test (TST) of 5 mm or greater, in those with a lymphocyte count of 2x10(9)/l or higher, and in those with haemoglobin of 10 g/dl or higher. There was no difference in mortality rates between the preventive therapy and placebo groups. The effect of preventive therapy declined after the first year of the study so that by 18 months the rates of TB in the treated groups were similar to that in the placebo group.\n This study has demonstrated that preventive therapy with either twice weekly isoniazid for 6 months or a combination of rifampicin and pyrazinamide for 3 months reduced the incidence of TB in HIV-infected persons in Zambia. No effect was observed on mortality. The effect was greatest in persons who had a positive TST or a lymphocyte count of 2x10(9)/l or greater, indicating that preventive therapy may be more effective in people with less advanced immunosuppression. The limited duration of the protective effect reported in this study raises the question of the need for lifelong preventive therapy or re-prophylaxis.", "To determine the efficacy of isoniazid 300 mg daily for 6 months in the prevention of tuberculosis in HIV-1-infected adults and to determine whether tuberculosis preventive therapy prolongs survival in HIV-1-infected adults.\n Randomized, double-blind, placebo-controlled trial in Nairobi, Kenya.\n Six hundred and eighty-four HIV-1-infected adults.\n Development of tuberculosis and death.\n Three hundred and forty-two subjects received isoniazid and 342 received placebo. The median CD4 lymphocyte counts at enrolment were 322 and 346 x 10(6)/l in the isoniazid and placebo groups, respectively. The overall median follow-up from enrolment was 1.83 years (range, 0-3.4 years). The incidence of tuberculosis in the isoniazid group was 4.29 per 100 person-years (PY) of observation [95% confidence interval (CI) 2.78-6.33] and 3.86 per 100 PY of observation (95% CI, 2.45-5.79) in the placebo group, giving an adjusted rate ratio for isoniazid versus placebo of 0.92 (95% CI, 0.49-1.71). The adjusted rate ratio for tuberculosis for isoniazid versus placebo for tuberculin skin test (TST)-positive subjects was 0.60 (95% CI, 0.23-1.60) and for the TST-negative subjects, 1.23 (95% CI, 0.55-2.76). The overall adjusted mortality rate ratio for isoniazid versus placebo was 1.18 (95% CI, 0.79-1.75). Stratifying by TST reactivity gave an adjusted mortality rate ratio in those who were TST-positive of 0.33 (95% CI, 0.09-1.23) and for TST-negative subjects, 1.39 (95% CI, 0.90-2.12).\n Overall there was no statistically significant protective effect of daily isoniazid for 6 months in the prevention of tuberculosis. In the TST-positive subjects, where reactivation is likely to be the more important pathogenetic mechanism, there was some protection and some reduction in mortality, although this was not statistically significant. The small number of individuals in this subgroup made the power to detect a statistically significant difference in this subgroup low. Other influences that may have diluted the efficacy of isoniazid include a high rate of transmission of new infection and rapid progression to disease or insufficient duration of isoniazid in subjects with relatively advanced immunosuppression. The rate of drug resistance observed in subjects who received isoniazid and subsequently developed tuberculosis was low.", "To determine the long-term effect of preventive therapy (PT) for tuberculosis on the rates of tuberculosis, mortality and HIV progression.\n In a randomized controlled trial, 1053 HIV-positive Zambian adults received isoniazid (H) for 6 months, rifampicin plus pyrazinamide (RZ) for 3 months, or a placebo. CD4 percentage, neopterin, absolute lymphocyte count and haemoglobin were measured from enrolment (absolute CD4 cell counts from 12 months after enrolment). Because PT reduced the incidence of tuberculosis, eligible placebo subjects were offered H. Here, tuberculosis and mortality rates are compared in the three original arms (intention to treat) using data beyond the end of the trial (average follow-up 3 years; maximum 7 years).\n There were 102 cases of tuberculosis and 281 deaths (rates 3.6 and 9.0/100 person-years, respectively). There was no significant difference between the tuberculosis rates in the H and RZ groups at any time. The effect of H/RZ on tuberculosis diminished over time (P = 0.011) but the cumulative risk of tuberculosis in the first 2.5 years was significantly lower in the H/RZ group than the placebo group (rate ratio 0.55; 95% confidence interval 0.32-0.93; P = 0.028). There was no significant effect of PT on mortality or progression markers. Tuberculosis was associated with an increased mortality (adjusted rate ratio 1.96; 95% confidence interval 1.21-3.18; P = 0.006).\n Both PT regimens protect against tuberculosis for at least 2.5 years but appear to have no effect on HIV progression or mortality. These results may be used in cost-effectiveness models of PT.", "Patients with human immunodeficiency virus (HIV) infection and latent tuberculosis are at substantial risk for the development of active tuberculosis. As a public health measure, prophylactic treatment with isoniazid has been suggested for HIV-infected persons who have anergy and are in groups with a high prevalence of tuberculosis.\n We conducted a multicenter, randomized, double-blind, placebo-controlled trial of six months of prophylactic isoniazid treatment in HIV-infected patients with anergy who have risk factors for tuberculosis infection. The primary end point was culture-confirmed tuberculosis.\n The study was conducted from November 1991 through June 1996. Over 90 percent of the patients had two or more risk factors for tuberculosis infection, and nearly 75 percent of patients were from greater New York City. After a mean follow-up of 33 months, tuberculosis was diagnosed in only 6 of 257 patients in the placebo group and 3 of 260 patients in the isoniazid group (risk ratio, 0.48; 95 percent confidence interval, 0.12 to 1.91; P=0.30). There were no significant differences between the two groups with regard to death, death or the progression of HIV disease, or adverse events.\n Even in HIV-infected patients with anergy and multiple risk factors for latent tuberculosis infection, the rate of development of active tuberculosis is low. This finding does not support the use of isoniazid prophylaxis in high-risk patients with HIV infection and anergy unless they have been exposed to active tuberculosis.", "Because of problems with adherence, toxicity, and increasing resistance associated with 6- to 12-month isoniazid regimens, an alternative short-course tuberculosis preventive regimen is needed.\n To compare a 2-month regimen of daily rifampin and pyrazinamide with a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with human immunodeficiency virus (HIV) infection.\n Randomized, open-label controlled trial conducted from September 1991 to May 1996, with follow-up through October 1997.\n Outpatient clinics in the United States, Mexico, Haiti, and Brazil.\n A total of 1583 HIV-positive persons aged 13 years or older with a positive tuberculin skin test result.\n Patients were randomized to isoniazid, 300 mg/d, with pyridoxine hydrochloride for 12 months (n = 792) or rifampin, 600 mg/d, and pyrazinamide, 20 mg/kg per day, for 2 months (n = 791).\n The primary end point was culture-confirmed tuberculosis; secondary end points were proven or probable tuberculosis, adverse events, and death, compared by treatment group.\n Of patients assigned to rifampin and pyrazinamide, 80% completed the regimen compared with 69% assigned to isoniazid (P<.001). After a mean follow-up of 37 months, 19 patients (2.4%) assigned to rifampin and pyrazinamide and 26 (3.3%) assigned to isoniazid developed confirmed tuberculosis at rates of 0.8 and 1.1 per 100 person-years, respectively (risk ratio, 0.72 [95% confidence interval, 0.40-1.31]; P = .28). In multivariate analysis, there were no significant differences in rates for confirmed or probable tuberculosis (P = .83), HIV progression and/or death (P = .09), or overall adverse events (P = .27), although drug discontinuation was slightly higher in the rifampin and pyrazinamide group (P = .01). Neither regimen appeared to lead to the development of drug-resistant tuberculosis.\n Our data suggest that for preventing tuberculosis in HIV-infected patients, a daily 2-month regimen of rifampin and pyrazinamide is similar in safety and efficacy to a daily 12-month regimen of isoniazid. This shorter regimen offers practical advantages to both patients and tuberculosis control programs.", "Tuberculosis (TB) preventive therapy is not effective in human immunodeficiency virus (HIV) infected adults with negative tuberculin skin tests (TSTs). However, there are insufficient data on patients with advanced HIV disease from high TB incidence areas.\n We conducted a randomised, double-blind, controlled trial comparing isoniazid (INH) with placebo among TST-negative adults with World Health Organization Stage 3 or 4 HIV disease. INH/placebo was administered for 12 months by patient-nominated supervisors. TST-positive participants were given open-label INH. Participants, who did not have access to antiretroviral therapy (ART), were followed up for 24 months with 6-monthly sputum culture and chest radiography.\n A total of 118 participants were enrolled: TST was negative in 98. In the randomised arms, the incidence of TB was 18/100 person-years (py) in the INH arm and 11.6/100 py in the placebo arm (hazard ratio 1.59, 95%CI 0.57-4.49). There were no significant differences in mortality, hospitalisation rate or CD4+ lymphocyte decline. INH/placebo adherence was 85%, and was significantly higher among participants with work-based treatment supervisors.\n We did not find any association between INH preventive therapy and reductions in incident TB among TST-negative adults with advanced HIV disease, but the study had limited statistical power. High levels of adherence were observed with patient-nominated supervisors.", "nan", "Tuberculosis occurring with human immunodeficiency virus (HIV) infection is a serious and growing public health problem. We have carried out a randomised clinical trial of a 12-month course of isoniazid plus vitamin B6 versus vitamin B6 alone in Port-au-Prince, Haiti, to assess the efficacy of isoniazid in preventing active tuberculosis in symptom-free HIV-infected individuals. The effect of prophylaxis on the development of HIV disease, AIDS, and death was also investigated. 118 subjects were assigned treatment with isoniazid plus B6 (n = 58) or B6 alone (n = 60) between 1986 and 1989. The treatment groups were similar at study entry in demographic, clinical, and immunological characteristics. Interim analysis in 1990 revealed no significant difference in tuberculosis outcome measures. Follow-up was continued until 1992, at which time significant protection by isoniazid against the development of tuberculosis was apparent, both for the whole study population and for subjects positive for purified protein derivative of tuberculin (PPD). The incidence of tuberculosis was lower in isoniazid recipients than in patients who received B6 alone (2.2 vs 7.5 per 100 person-years). The relative risk of tuberculosis was 3.4 (95% CI 1.1-10.6) for B6 alone versus isoniazid plus B6 (p < 0.05). Isoniazid also delayed progression to HIV disease and AIDS and death. Thus isoniazid effectively decreases the incidence of tuberculosis and delays the onset of HIV-related disease in symptom-free HIV-seropositive individuals. Isoniazid prophylaxis should be considered for HIV-seropositive, PPD-positive subjects, and may also be appropriate for PPD-negative patients in areas where tuberculosis is highly endemic." ]

[ "19261295", "17693179" ]

[ "Efficacy of sapropterin dihydrochloride in increasing phenylalanine tolerance in children with phenylketonuria: a phase III, randomized, double-blind, placebo-controlled study.", "Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study." ]

[ "To evaluate the ability of sapropterin dihydrochloride (pharmaceutical preparation of tetrahydrobiopterin) to increase phenylalanine (Phe) tolerance while maintaining adequate blood Phe control in 4- to 12-year-old children with phenylketonuria (PKU).\n This international, double-blind, randomized, placebo-controlled study screened for sapropterin response among 90 enrolled subjects in Part 1. In Part 2, 46 responsive subjects with PKU were randomized (3:1) to sapropterin, 20 mg/kg/d, or placebo for 10 weeks while continuing on a Phe-restricted diet. After 3 weeks, a dietary Phe supplement was added every 2 weeks if Phe control was adequate.\n The mean (+/-SD) Phe supplement tolerated by the sapropterin group had increased significantly from the pretreatment amount (0 mg/kg/d) to 20.9 (+/-15.4) mg/kg/d (P < .001) at the last visit at which subjects had adequate blood Phe control (<360 micromol/L), up to week 10. Over the 10-week period, the placebo group tolerated only an additional 2.9 (+/-4.0) mg/kg/d Phe supplement; the mean difference from the sapropterin group (+/-SE) was 17.7 +/- 4.5 mg/kg/d (P < .001). No severe or serious related adverse events were observed.\n Sapropterin is effective in increasing Phe tolerance while maintaining blood Phe control and has an acceptable safety profile in this population of children with PKU.", "Early and strict dietary management of phenylketonuria is the only option to prevent mental retardation. We aimed to test the efficacy of sapropterin, a synthetic form of tetrahydrobiopterin (BH4), for reduction of blood phenylalanine concentration.\n We enrolled 89 patients with phenylketonuria in a Phase III, multicentre, randomised, double-blind, placebo-controlled trial. We randomly assigned 42 patients to receive oral doses of sapropterin (10 mg/kg) and 47 patients to receive placebo, once daily for 6 weeks. The primary endpoint was mean change from baseline in concentration of phenylalanine in blood after 6 weeks. Analysis was on an intention-to-treat basis. The study is registered with ClinicalTrials.gov, number NCT00104247.\n 88 of 89 enrolled patients received at least one dose of study drug, and 87 attended the week 6 visit. Mean age was 20 (SD 9.7) years. At baseline, mean concentration of phenylalanine in blood was 843 (300) micromol/L in patients assigned to receive sapropterin, and 888 (323) micromol/L in controls. After 6 weeks of treatment, patients given sapropterin had a decrease in mean blood phenylalanine of 236 (257) micromol/L, compared with a 3 (240) micromol/L increase in the placebo group (p<0.0001). After 6 weeks, 18/41 (44%) patients (95% CI 28-60) in the sapropterin group and 4/47 (9%) controls (95% CI 2-20) had a reduction in blood phenylalanine concentration of 30% or greater from baseline. Blood phenylalanine concentrations fell by about 200 micromol/L after 1 week in the sapropterin group and this reduction persisted for the remaining 5 weeks of the study (p<0.0001). 11/47 (23%) patients in the sapropterin group and 8/41 (20%) in the placebo group experienced adverse events that might have been drug-related (p=0.80). Upper respiratory tract infections were the most common disorder.\n In some patients with phenylketonuria who are responsive to BH4, sapropterin treatment to reduce blood phenylalanine could be used as an adjunct to a restrictive low-phenylalanine diet, and might even replace the diet in some instances." ]

[ "9627585", "8757574", "8115195", "7669374", "14612478", "10201714", "10194990", "8101584", "1468386", "8949692" ]

[ "Physiological, hormonal, and behavioral responses to a single fentanyl dose in intubated and ventilated preterm neonates.", "Routine use of fentanyl infusions for pain and stress reduction in infants with respiratory distress syndrome.", "Pain relief can reduce hypoxemia in distressed neonates during routine treatment procedures.", "Morphine increases synchronous ventilation in preterm infants.", "Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial.", "Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates.", "Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease.", "Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies.", "Effect of morphine and pancuronium on the stress response in ventilated preterm infants.", "Alfentanil as procedural pain relief in newborn infants." ]

[ "To study the responses of ventilated preterm neonates to a single dose of opioid.\n In a randomized, double-blind, controlled trial, 22 mechanically ventilated preterm infants (< or = 32 weeks) were observed before medication and at 30 and 60 minutes after administration of fentanyl (3 micrograms/kg) or placebo. Heart rate, blood pressure, arterial blood gases, ventilator settings, and behavioral measures (Neonatal Facial Coding System and Modified Postoperative Comfort Score) were recorded during each period. Blood cortisol, growth hormone, glucose, and lactate were measured before and at 60 minutes after analgesia. Behavioral measures were assessed at the bedside and from video films recorded during each observation period.\n Patients presented high basal levels of cortisol, growth hormone, and lactate. Behavioral scales indicated the presence of pain before any medication. In the fentanyl group, the maximum and minimum heart rate decreased and growth hormone level increased after analgesia. At the video analysis of behavioral measures, postoperative comfort score increased and neonatal facial coding system score decreased in the fentanyl group.\n Single doses of fentanyl analgesia can reduce the physiologic/behavioral measures of pain and stress associated with mechanical ventilation in preterm infants.", "To determine whether fentanyl infusions given to premature infants with respiratory distress syndrome reduce stress and improve long- and short-term outcome.\n Twenty premature infants undergoing mechanical ventilation for respiratory distress syndrome were randomly assigned, in a double-blind fashion, to receive fentanyl by continuous infusion or a volume-matched placebo infusion. A behavioral state score was used to assess the infants' behavior. Cortisol and 11-deoxycortisol levels were measured as physiologic markers of stress. Urinary 3-methyl histidine/creatinine molar ratio was determined and the fractional excretion of urea was measured to assess catabolic state. Ventilatory indexes were recorded for each infant.\n Infants receiving fentanyl showed significantly lower behavioral state scores (p < 0.04) and lower heart rates (p < 0.001) than those receiving placebo. 11-Deoxycortisol levels were lower in the fentanyl group on days 3, 4, and 5 of the study (p < 0.003). 3-Methyl histidine/creatinine ratios and fractional excretion of urea were not significantly different between the two groups. On the third day of the study, infants receiving fentanyl required a higher ventilator rate (p < 0.01), higher peak inspiratory pressures (p < 0.001), and higher positive end-expiratory pressure (p < 0.0001) than those receiving placebo. There was no difference in long-term outcome with respect to the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, or sepsis or with respect to the duration of ventilator use.\n Although there was a reduction in stress markers in the infants receiving fentanyl, we were unable to demonstrate an improvement in catabolic state or long-term outcome. In addition, the infants receiving fentanyl required higher ventilatory support in the early phase of respiratory distress syndrome than did those receiving placebo.", "To determine whether the use of opioids could reduce the hypoxemia and hemodynamic instability associated with routine intensive care procedures in neonates with respiratory distress.\n Randomized and placebo-controlled study.\n Physiological, plasma beta-endorphin, cortisol, and glucose responses to routine treatment procedures were studied in 84 mechanically ventilated distressed neonates randomized into groups receiving 1 mg/kg meperidine or 0.9% saline 15 minutes before tracheal suction or routine nursing care.\n The duration of hypoxemia (transcutaneous partial pressure of O2 < 6.6 kPa (< 50 mm Hg) and/or arterial blood oxygen saturation < 80%) during treatment procedures was significantly longer in the saline group (mean 82 vs 36 seconds, P = .001) and distress quantified by a novel behavioral scoring method was much higher. Changes in arterial blood pressure, heart rate, or plasma beta-endorphin, cortisol, and glucose concentration did not show any statistically significant differences between the groups.\n Newborns with respiratory difficulties often suffer from hypoxemia during essential treatment procedures. The use of opioid analgesia may reduce the duration of hypoxemia and the associated distress and, therefore, may improve the long-term results of neonatal intensive care.", "To examine the short-term cardiorespiratory effects of intravenous morphine infusion in ventilated preterm infants.\n A randomized double-blind placebo-controlled trial in a neonatal intensive care unit. Twenty-six preterm infants (29-36 weeks gestation) with hyaline membrane disease requiring ventilatory assistance on the first day after birth were included in the study. A loading dose of morphine 100 micrograms/kg over 30 min followed by a continuous intravenous infusion at 10 micrograms/kg per hour was given. Primary measures were heart rate, blood pressure, respiratory rate and interaction of spontaneous respiration with mechanical ventilation. Secondary measures were durations of oxygen therapy, ventilator therapy and hospitalization as well as incidence of bronchopulmonary dysplasia, periventricular haemorrhage and pneumothorax.\n Morphine-treated infants spent a significantly greater percentage of total ventilated time breathing in synchrony with their ventilators (median [IQ] = 72[58-87] vs 31[17-51]%; P = 0.0008). Heart rate and respiratory rate, but not blood pressure, were reduced in morphine-treated infants. Duration of oxygen therapy was reduced (median [IQ] = 4.5[3-7] vs 8[4.75-12.5] days; P = 0.046).\n Intravenous morphine infusion increases synchronicity of spontaneous and ventilator-delivered breaths in preterm infants. Morphine reduces heart rate and respiratory rate without reducing blood pressure, and may help to reduce duration of oxygen therapy in preterm infants with hyaline membrane disease.", "Newborns admitted to neonatal intensive care units (NICUs) undergo a variety of painful procedures and stressful events. Because the effect of continuous morphine infusion in preterm neonates has not been investigated systematically, there is confusion regarding whether morphine should be used routinely in this setting.\n To evaluate the effects of continuous intravenous morphine infusion on pain responses, incidence of intraventricular hemorrhage (IVH), and poor neurologic outcome (severe IVH, periventricular leukomalacia, or death).\n A randomized, double-blind, placebo-controlled trial conducted between December 2000 and October 2002 in 2 level III NICUs in the Netherlands of 150 newborns who had received ventilatory support (inclusion criteria: postnatal age younger than 3 days and ventilation for less than 8 hours; exclusion criteria: severe asphyxia, severe IVH, major congenital malformations, and administration of neuromuscular blockers).\n Intravenous morphine (100 microg/kg and 10 microg/kg per hour) or placebo infusion was given for 7 days (or less because of clinical necessity in several cases).\n The analgesic effect of morphine, as assessed using validated scales; the effect of morphine on the incidence of IVH; and poor neurologic outcome.\n The analgesic effect did not differ between the morphine and placebo groups, judging from the following median (interquartile range) pain scores: Premature Infant Pain Profile, 10.1 (8.2-11.6) vs 10.0 (8.2-12.0) (P =.94); Neonatal Infant Pain Scale, 4.8 (3.7-6.0) vs 4.8 (3.2-6.0) (P =.58); and visual analog scale, 2.8 (2.0-3.9) vs 2.6 (1.8-4.3) (P =.14), respectively. Routine morphine infusion decreased the incidence of IVH (23% vs 40%, P =.04) but did not influence poor neurologic outcome (10% vs 16%, P =.66). In addition, analyses were adjusted for the use of additional open-label morphine (27% of morphine group vs 40% of placebo group, P =.10).\n Lack of a measurable analgesic effect and absence of a beneficial effect on poor neurologic outcome do not support the routine use of morphine infusions as a standard of care in preterm newborns who have received ventilatory support. Follow-up is needed to evaluate the long-term effects of morphine infusions on the neurobehavioral outcomes of prematurity.", "Preterm neonates are exposed to multiple painful procedures after birth and exhibit acute physiological responses to pain. Occurrence of early intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of pain and stress in the multifactorial causation of severe intraventricular hemorrhage and periventricular leukomalacia. We proposed that such neurologic outcomes in preterm neonates who require ventilatory support may be reduced by morphine analgesia or midazolam sedation compared with a placebo.\n To define the incidence of clinical outcomes in the target study population, to estimate the effect size and adverse effects associated with analgesia and sedation, and to calculate the sample size for a definitive test of this hypothesis.\n Sixty-seven preterm neonates were randomized in a pilot clinical trial from 9 centers. Neonates of 24 to 32 weeks gestation were eligible if they had been intubated and required ventilatory support for less than 8 hours and if they were enrolled within 72 hours after birth. Exclusion criteria included major congenital anomalies, severe intrapartum asphyxia, and participation in other research studies. Severity of illness was assessed by the Clinical Risk Index for Babies, and neonates were randomized to receive continuous infusions of morphine sulfate, midazolam hydrochloride, or 10% dextrose (placebo). Masked study medications were continued as long as clinically necessary, then weaned and stopped according to predefined criteria. Levels of sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile scores) were measured before, during, and 12 hours after discontinuation of drug infusion. Cranial ultrasound examinations were performed as part of routine practice, and poor neurologic outcomes were defined as neonatal death, severe intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia.\n No significant differences occurred in the demographic, clinical, and socioeconomic variables related to mothers and neonates in the 3 groups or in the severity of illness at birth as measured by Clinical Risk Index for Babies scores. Two neonates in the placebo group and 1 neonate in the midazolam group died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in the morphine group (likelihood ratio chi2 = 7.04, P = .03). Secondary clinical outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were similar in the 3 groups. Responses elicited by endotracheal tube suction (Premature Infant Pain Profile scores) were significantly reduced during the morphine (P<.001) and midazolam (P = .002) infusions compared with the placebo group.\n This pilot trial suggests that preemptive analgesia given by continuous low-dose morphine infusion may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Limitations in the sample size of this pilot study suggest that these results should be confirmed in a large multicenter randomized trial.", "To evaluate the effects of low dose fentanyl infusion analgesia on behavioural and neuroendocrine stress response and short term outcome in premature infants ventilated for hyaline membrane disease.\n Twenty seven ventilated preterm infants were randomly assigned to receive a mean fentanyl infusion of 1.1 (0.08 SE) micrograms/kg/h for 75 (5) hours, and 28 untreated infants were considered a control group. A behavioural sedation score was used to assess the infants' behaviour. Urinary metanephrine and the normetanephrine:creatinine molar ratio were determined at 0, 24, 48 and 72 hours. Outcome data and ventilatory indexes were recorded for each infant.\n The fentanyl group showed significantly lower behavioural stress scores and O2 desaturations than controls and lower urinary concentrations of metanephrine and normetanephrine at 24, 48, 72 hours. The two groups showed no significant difference in ventilatory variables or short term outcome.\n A short course of low dose fentanyl infusion reduces behavioural sedation scores, O2 desaturations and neuroendocrine stress response in preterm ventilated infants.", "A sick premature baby who requires intensive care will undergo many uncomfortable procedures. It is now accepted that such babies perceive pain and need adequate analgesia, but little is known about the effects of sedation in these patients. We investigated the use of morphine to provide analgesia and sedation for ventilated preterm babies in a randomised, double-blind, placebo-controlled trial. 41 mechanically ventilated babies who had been treated with surfactant (Curosurf) for hyaline membrane disease were randomly assigned morphine in 5% dextrose (100 micrograms/kg per h for 2 h followed by 25 micrograms/kg per h continuous infusion) or 5% dextrose (placebo). Plasma catecholamine concentrations were measured 1 h after the first dose of surfactant and 24 h later. Blood pressure was measured at study entry and after 6 h. The morphine and placebo groups showed no differences in method of delivery, Apgar scores, birthweight, gestation, or catecholamine concentrations at baseline. Morphine-treated babies showed a significant reduction in adrenaline concentrations during the first 24 h (median change -0.4 [95% CI -1.1 to -0.3] nmol/L p < 0.001), which was not seen in the placebo group (median change 0.2 [-0.6 to 0.6] nmol/L, p = 0.79). There was a non-significant reduction in noradrenaline concentration in the morphine group. Blood pressure showed a slight but non-significant fall (median -4 mm Hg) in morphine-treated babies. The incidence of intraventricular haemorrhage, patent ductus arteriosus, and pneumothorax, the number of ventilator days, and the numbers of deaths did not differ significantly between the groups. Morphine, in the dose regimen we used, is safe and effective in reducing adrenaline concentrations in preterm ventilated babies.", "Ninety-five premature newborns who had hyaline membrane disease and were struggling against the ventilator were randomised to one of three treatment groups: morphine (group M), pancuronium (group P) or morphine with pancuronium (group M+P). The dose of morphine was 50 micrograms/kg per h but was increased to 100 micrograms/kg per h in group M infants if they continued to struggle. The dosage of pancuronium was 100 micrograms/kg given as required to inhibit spontaneous respiration. Plasma catecholamine levels were measured on entry and at 24 h. Blood pressure and ventilatory requirements were determined on entry and at 6 h. The clinical outcome of the infants was documented. Group M infants (n = 29) showed a significant reduction in noradrenaline levels (median change -2.2 nmols/l (range -47.2 to +7.2 nmols/l), although seven were withdrawn from this group because of failure to settle. Group P (n = 28) and group M+P (n = 38) showed no significant change in noradrenaline levels. Comparison between the groups showed that group M infants had a significant reduction in noradrenaline levels compared with group P. The immediate effects of treatment on blood pressure and ventilatory requirements were similar in the three groups. The clinical outcome did not differ for any of the measured parameters. When adequate sedation is achieved, morphine may reduce the stress of newborn intensive care.", "To assess the need for, and the suitability of, alfentanil for pain relief during tracheal suction used in assisted ventilation in newborn infants.\n In a randomised, controlled, double blind, crossover trial, placebo (10 micrograms/kg) and 20 micrograms/kg alfentanil were infused in random order two minutes before three separate endotracheal suctions, at least six hours apart, to 10 infants. Measurements were made of physiological variables, behaviour, and stress hormones.\n After placebo infusion heart rate significantly increased (median 14; interquartile range 12-16 beats/minute) as did behavioural pain score (5; 3-5). Alfentanil (20 micrograms/kg) attenuated the heart rate increase, normalised the pain score, and caused a decrease in plasma adrenaline activity (0.3; 0.2-0.7 nmol/l). Noradrenaline concentration showed a nonsignificant decreasing trend with increasing alfentanil dose and beta endorphin was unchanged. Rigidity was noted in the placebo (n = 2), 10 micrograms/kg (n = 2), and 20 micrograms/kg (n = 5) alfentanil groups, respectively.\n Tracheal suction is a painful procedure. The dose of alfentanil required for pain relief (20 micrograms/kg) causes a high incidence of rigidity and thus should be used only with muscle relaxant." ]

[ "10521736" ]

[ "Maintenance oral nifedipine for preterm labor: a randomized clinical trial." ]

[ "This study was undertaken to evaluate the efficacy of maintenance oral nifedipine in patients initially treated with intravenous magnesium sulfate for preterm labor.\n Patients with a diagnosis of preterm labor between 24 and 33.9 weeks' gestation were randomly assigned to receive either maintenance tocolytic therapy with oral nifedipine (20 mg every 4-6 hours) or no treatment (control) after discontinuation of magnesium tocolysis. Pregnancy and neonatal outcomes were evaluated. A sample size of 50 patients was required to detect a 10-day difference in mean time gained (beta =.2, alpha =.05). Statistical analyses were based on intent to treat. The t, chi(2), and Fisher exact tests were performed.\n Seventy-four patients were randomly assigned to receive either oral nifedipine (n = 37) or no treatment (n = 37). There were no statistically significant differences in age, race, parity, preterm delivery risk factors, enrollment gestational age, results of cervical examination, delivery gestational age, time gained, or neonatal complications between the groups. Delivery gestational age (mean +/- SD) was 35.4 +/- 3.2 weeks for patients randomly assigned to receive nifedipine and 35.3 +/- 3.2 weeks for patients who received no treatment (P =.9). Time gained during pregnancy was 37 +/- 23.9 days in the nifedipine group and 32.8 +/- 20.4 days in the control group (P =.4).\n Maintenance therapy with oral nifedipine does not significantly prolong pregnancy in patients initially treated with intravenous magnesium sulfate for preterm labor." ]

[ "9764623", "1945215", "8416460", "17763271" ]

[ "Effect of maternal hydration on oligohydramnios: a comparison of three volume expansion methods.", "Maternal hydration increases amniotic fluid index.", "Maternal hydration increases amniotic fluid index in women with normal amniotic fluid.", "A randomized clinical trial comparing the effect of maternal intravenous hydration and placebo on the amniotic fluid index in oligohydramnios." ]

[ "To determine the effect of maternal hydration with intravenous (i.v.) isotonic fluid, i.v. hypotonic fluid, and oral water on amniotic fluid index (AFI) in women with oligohydramnios.\n Patients with low AFI and gestational age over 35 weeks without maternal complications were randomized into four groups (2 L/2 h i.v. isotonic fluid, 2 L/2 h i.v. hypotonic fluid, 2 L/2 h oral water, control). Maternal plasma osmolality, AFI, hematocrit, and hemoglobin concentration were measured before and after hydration.\n Eighty-four patients (n=21/group) completed the study without any maternal adverse effects. The mean increase in AFI after hydration was significantly greater in the i.v. hypotonic and oral water groups (2.8+/-1.9, P < .001; 3.8 +/-1.9, P < .001, respectively), but not in the i.v. isotonic group (0.5+/-1.1), compared with the control group (0.5+/-1.1). Significant decreases in maternal hematocrit and hemoglobin concentration were found only after i.v. isotonic hydration (32.0+/-2.9 to 29.5+/-2.3, P < .001; 11.0+/-1.6 to 10.1+/-1.4, P < .001, respectively). Changes in maternal osmolality correlated with the changes in AFI in both the i.v. hypotonic group (r=.58, P < .001) and oral water group (r =.63, P < .001).\n Maternal hydration with either i.v. hypotonic fluid or oral water increases AFI in oligohydramnios. Maternal osmotic change rather than maternal volume expansion had a more direct impact on increasing amniotic fluid volume with short-term acute hydration.", "Although adequate amniotic fluid (AF) volume is considered an important aspect of fetal well-being, the etiology of decreased AF volume is not well understood. A randomized blinded trial was designed to examine our hypothesis that maternal hydration would increase the AF index in women with low AF indexes. Women seen in our testing centers were randomized into control or hydration groups. The control group was instructed to drink their normal amount of fluid; the hydration group was instructed to drink 2 L of water, in addition to their usual amount of fluid, 2-4 hours before the post-treatment AF index. The women returned for the post-treatment AF index the same or following day. The mean post-treatment AF index was significantly greater in the hydration group (6.3 versus 5.1; P less than .01), as was the mean change in AF index (post-treatment AF index--pre-treatment AF index: 1.5 versus 0.31; P less than .01). These findings suggest that maternal oral hydration increases AF volume in women with decreased fluid levels.", "To test the hypothesis that maternal oral hydration would increase the amniotic fluid (AF) index in pregnancies with normal AF.\n Forty women with a normal AF index (7.0-24.0 cm) were randomized to either the control or hydration group. Women in the hydration group drank 2 L of water and returned for the post-treatment AF index in 4-6 hours, whereas women in the control group drank only 100 mL of water during the same time period. The investigator performing the AF index was blinded to the subject's group. The pre- and post-treatment AF indexes and maternal urine specific gravities were compared between the groups.\n The mean AF index in the hydration group increased significantly by 3.0 +/- 2.4 cm (P < or = .0001) whereas it declined significantly by 1.5 +/- 2.7 cm in the control group (P < or = .02). The maternal urine specific gravities also changed significantly in the expected direction, with those in the hydration group decreasing and those in the control group increasing (P < or = .0001). There was a regression coefficient of -0.6 (P < or = .0001) between the change in urine specific gravity and the change in AF index. The mean time between the pre- and post-treatment AF indexes was not different between the groups.\n Maternal oral hydration increased the AF index by approximately 16%, whereas fluid restriction decreased the AF index by 8% in women with normal AF. These findings support previous data that maternal hydration increased the AF index by 31% in women with decreased AF and suggest that maternal fluid volume or osmolality may have a role in maintaining the AF volume.", "To compare the treatment of acute intravenous hydration with placebo in term pregnant women manifesting oligohydramnios.\n All patients with oligohydramnios who met the inclusion criteria were offered participation in this randomized, double-blind, placebo-controlled study. After ruling out rupture of membranes and maternal and fetal complications, we recruited 44 women with third trimester singleton pregnancies having an amniotic fluid index (AFI) of less than 6. Patients were randomized into treatment or control groups. Patients in the treatment group received a continuous intravenous infusion of (1/2) normal saline (NS) at a rate of 1000 mL/h for two hours. Patients in the placebo group received an intravenous infusion of (1/2) NS at 10 mL/h for two hours. The AFI was re-assessed by the same sonographer one hour after the hydration was completed. Both the patient and the examiner were blinded to the study groups.\n Maternal age, parity, gestational age, and birth weight were not significantly different between the two groups. The AFI increased significantly in both treatment (3.8 +/- 1.2 vs. 5.3 +/- 2.5, p < 0.05) and placebo (4 +/- 1.3 vs. 5.5 +/- 2.4, p < 0.05) groups. Moreover, the changes in AFI did not significantly differ between the treatment and the placebo groups (1.2 +/- 2.1 vs. 1.5 +/- 2.1, respectively; p > 0.05).\n There are statistically significant short-term increases in the AFI in patients with oligohydramnios whether the patients are treated with intravenous fluids or not. The short-term increase in AFI may reflect physiologic diurnal variations in the amniotic fluid." ]

[ "3117190", "9472506", "12558203", "3386568", "9458567", "3187497", "2737877", "12042083", "12196620" ]

[ "HIV testing: changing trends.", "Uptake and acceptability of antenatal HIV testing: randomised controlled trial of different methods of offering the test.", "Using message framing to motivate HIV testing among low-income, ethnic minority women.", "The \"Grim Reaper\" campaign.", "Evaluation of the Quebec Public Information Campaign and Human Immunodeficiency Virus (HIV) Antibody Screening Program directed to persons transfused between 1978 and 1985.", "HIV testing in Glasgow Genito-Urinary Medicine Clinics 1985-1987.", "Epidemiological observations in the AIDS clinic at the Hadassah University Hospital in Jerusalem.", "Can targeted HIV testing campaigns alter health-seeking behaviour?", "Is a general women's health promotion program as effective as an HIV-intensive prevention program in reducing HIV risk among Hispanic women?" ]

[ "nan", "To determine the uptake and acceptability of different methods of a universal offer of voluntary HIV testing to pregnant women.\n Randomised controlled trial involving four combinations of written and verbal communication, followed by the direct offer of a test. The control group received no information and no direct offer of a test, although testing was available on request.\n Hospital antenatal clinic covering most of the population of the city of Edinburgh.\n 3024 pregnant women booking at the clinic over a 10 month period.\n Uptake of HIV testing and women's knowledge, satisfaction, and anxiety.\n Uptake rates were 6% for those in the control group and 35% for those directly offered the test. Neither the style of leaflet nor the length of discussion had an effect on uptake. Significant independent predictors of uptake were a direct test offer; the midwife seen; and being unmarried, previously tested, and younger age. Knowledge of the specific benefits of testing increased with the amount of information given, but neither satisfaction nor anxiety was affected by the type of offer.\n The universal offer of HIV testing is not intrusive and is acceptable to pregnant women. A policy of offering the HIV test to all women resulted in higher uptake and did not increase anxiety or dissatisfaction. Uptake depends more on the midwife than the method of offering the test. Low uptake rates and inadequate detection of HIV infection point to the need to assess a more routine approach to testing.", "This study compared the effectiveness of 4 videotaped educational programs designed to motivate HIV testing among low-income, ethnic minority women. Four hundred eighty women were assigned randomly to watch one of 2 gain-framed or 2 loss-framed videos. Consistent with prospect theory, participants' perceptions of the certainty of the outcome of an HIV test moderated the effects of framing on self-reported testing behavior 6 months after video exposure. Among participants who reported being certain of the test's outcome, those who saw a gain-framed video reported a higher rate of testing than those who saw a loss-framed message. Among women who perceived the outcome of HIV testing as relatively uncertain, gain- and loss-framed videos led to similar rates of self-reported testing, with some advantage for the loss-framed message.", "nan", "This study aimed to determine the number and characteristics of the blood recipients tested for HIV infection as a result of the provincial HIV antibody screening program (directed to persons transfused between 1978 and 1985 and their contacts) and to estimate the rate of HIV seroprevalence among them. All physicians in the province of Quebec were provided with a special prescription form for HIV testing of eligible patients. Over a six-month period, a total of 6,348 special prescription forms were used. The HIV seroprevalence was 0.13% (95% confidence interval: 0.04% to 0.2%). We estimated an increase of 16.5% (12,061 tests) in the number of HIV tests related to the program. These results were consistent with those found by similar programs elsewhere in Canada but less than expected. Multiple strategies, including direct notification of transfusion recipients, particularly pediatric patients, are probably necessary to reach infected blood recipients still unaware of their infection.", "Between 1 March 1985 and 28 February 1987, 1659 patients attending Glasgow Genito-Urinary Medicine (GUM) Clinics were tested for antibodies to human immunodeficiency virus (HIV). Forty (2.4%) were positive. Thirty-seven of these were homosexual (36/37) or bisexual (1/37) males. The overall prevalence of antibodies to HIV in this group was 3.9% (37/940) and showed no significant increase over the two year period. Following the extensive media campaign in October 1986, the total numbers tested each month rose from an average of around 50, to 144 in December 1986. There was a further rise to 220 in March 1987 coinciding with AIDS week in March 1987. Since then the numbers have again declined. Before the October campaign, 70% of these tested (692/990) were homo/bisexual males. After the campaign the number of heterosexual males and females rose sharply, accounting for 68% of these tested.", "Of the first 395 attendees at the AIDS clinic in Jerusalem, 32% were homo/bisexuals, 4% i.v. drug abusers (IVDAs), 24% persons with minimal risk for AIDS and 38% were persons having no risk. Human immunodeficiency virus (HIV) antibody rates were 7% for homosexuals, 29% for IVDAs, 1% for persons with minimal risk and 0% for persons at no risk. Israeli homosexuals had a significantly greater risk for HIV infection (9 of 35) if they had sexual contact with non-Israelis as compared with homosexuals who had contact with local partners only (0/91, P less than 0.001). The mean number of attendees per month increased by 431% during the 4 months following the first prime-time television program on AIDS. The largest mean increases occurred among persons at no risk (1 to 27.2), those with minimal risk (2.5 to 16.5), and among women (1.25 to 20.0). This report indicates that HIV infection among Israeli homosexuals has not yet reached U.S. proportions. It also shows that the TV program raised anxiety concerning AIDS among the general public, and probably encouraged the public to use HIV testing as part of a general health screening program.", "This paper describes the evaluation of 'gimme 5 minutes' a multimedia HIV testing campaign aimed at gay and bisexual men in London particularly targeting those of Black and South European Origin and those under the age of 25 years old using peer images. The text linked a summary of the key issues of a pre-test discussion with detailed information on how to access testing at a specified testing centre (campaign clinic). The number and demographics of men who reported sex with men (MSM) testing at the campaign clinic were monitored and compared with those testing at two other central London clinics. There was a 4.5-fold rise (p < 0.001) in MSM testing at the campaign clinic. Increases were proportionately greater in the sub-populations targeted with peer images: South European origin, 14-fold rise (p < 0.001), Black origin, 6.5-fold rise (p = 0.003), and MSM under 25 years old, 9.5-fold rise (p < 0.001). There were no significant changes in the number of MSM testing for HIV at the two other central London clinics studied. The results suggest that including detailed information about accessing testing services may be a vital ingredient in the success of media campaigns focusing on HIV testing.", "This study aimed to assess whether participants in an HIV-intensive prevention program and participants in a general women's health promotion program reported greater HIV risk-reduction than participants in a wait-list control group immediately following program participation and at three-month follow-up.\n The authors studied 162 Hispanic women ages 18 to 35 years, most of them immigrants. Three-fourths of the sample (74%) reported earning less than $800 a month, 29% did not have a high school degree, and 90% had children. Data were gathered through surveys at baseline, at intervention completion, and at three-month follow-up. Information was collected on sociodemographics, HIV risk factors, and risk behaviors. Crude and adjusted (for demographics and dose) logistic regression analyses were used to assess program effects on participants' risk reduction.\n Crude logistic regression analyses reveal that both programs resulted in increased condom use at post-test and follow-up. Only participants in the HIV-intensive prevention program reported increased safer sex negotiation at post-test and follow-up, however, and only participants in the women's health promotion program reported increased HIV testing at post-test.\n Both interventions increased condom use. The HIV-intensive prevention program appeared to be more effective in promoting safer sex negotiation, and the women's health promotion program appeared more effective in promoting HIV testing. The findings suggest that both approaches may be viable ways to package HIV prevention for short-term behavior change in this population." ]

[ "21211558", "17493509", "14723327" ]

[ "Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients.", "The effect of Momordica charantia capsule preparation on glycemic control in type 2 diabetes mellitus needs further studies.", "Evaluation of the efficacy of bitter gourd (momordica charantia) as an oral hypoglycemic agent--a randomized controlled clinical trial." ]

[ "Bitter melon (Momordica charantia L.) has been widely used as an traditional medicine treatment for diabetic patients in Asia. In vitro and animal studies suggested its hypoglycemic activity, but limited human studies are available to support its use.\n This study was conducted to assess the efficacy and safety of three doses of bitter melon compared with metformin.\n This is a 4-week, multicenter, randomized, double-blind, active-control trial. Patients were randomized into 4 groups to receive bitter melon 500 mg/day, 1,000 mg/day, and 2,000 mg/day or metformin 1,000 mg/day. All patients were followed for 4 weeks.\n There was a significant decline in fructosamine at week 4 of the metformin group (-16.8; 95% CI, -31.2, -2.4 μmol/L) and the bitter melon 2,000 mg/day group (-10.2; 95% CI, -19.1, -1.3 μmol/L). Bitter melon 500 and 1,000 mg/day did not significantly decrease fructosamine levels (-3.5; 95% CI -11.7, 4.6 and -10.3; 95% CI -22.7, 2.2 μmol/L, respectively).\n Bitter melon had a modest hypoglycemic effect and significantly reduced fructosamine levels from baseline among patients with type 2 diabetes who received 2,000 mg/day. However, the hypoglycemic effect of bitter melon was less than metformin 1,000 mg/day.\n Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.", "Momordica charantia, locally known as Ampalaya, is being widely used and advertised for its hypoglycemic effects. However, to date, no large clinical trial has been published on the efficacy of any type of preparation. The main objective of this study is to determine if addition of M. charantia capsules to standard therapy can decrease glycosylated hemoglobin (hemoglobin A1c or HbA1c) levels in diabetic patients with poor sugar control.\n A randomized, double-blind, placebo-controlled trial was conducted between April and September 2004 at the outpatient clinics of the Philippine General Hospital. The trial included 40 patients, 18 years old and above, who were either newly diagnosed or poorly controlled type 2 diabetics with A1c levels between 7% and 9%. On top of the standard therapy, the patients were randomized to either M. charantia capsules or placebo. The treatment group received two capsules of M. charantia three times a day after meals, for 3 months. The control group received placebo at the same dose. The primary efficacy endpoint was change in the A1c level in the two groups. The secondary efficacy endpoints included its effect on fasting blood sugar, serum cholesterol, and weight. Safety endpoints included effects on serum creatinine, hepatic transaminases (Alanine aminotransferase/ALT and Aspartate aminotransferase/AST), sodium, potassium, and adverse events.\n Baseline characteristics between the treatment and control groups were similar. The difference in mean change in A1c between the two groups was 0.22% in favor of M. charantia (95% CI: -0.40 to 0.84) with P=0.4825. There was no significant effect on mean fasting blood sugar, total cholesterol, and weight or on serum creatinine, ALT, AST, sodium, and potassium. There were few adverse events and these were generally mild.\n This is the first randomized controlled trial to shed light on the issue concerning the hypoglycemic effects of M. charantia. The investigators targeted a 1% decline in A1c at the outset with an estimated power of 88%. With the observed decline of 0.24%, the achieved power was only 11%. For this reason, we are unable to make a definite conclusion about the effectiveness of M. charantia. However, the results of this study can be used estimate the sample size for bigger studies.", "nan" ]

[ "8416463" ]

[ "Preterm premature rupture of membranes: a randomized study of home versus hospital management." ]

[ "To compare length of latency period, gestational age at delivery, and safety in a carefully selected group of patients with preterm premature rupture of the membranes (PROM) randomized to home versus hospital management.\n After meeting strict inclusion criteria, 67 patients with preterm PROM were randomized by sealed envelope to home versus hospital expectant management. The groups were managed similarly with pelvic and bed rest. Management included recording of temperature and pulse every 6 hours, daily charting of fetal movements, twice-weekly nonstress test and complete blood count, and weekly ultrasound and visual examination of the cervix.\n There was no significant difference in clinical characteristics or perinatal outcome between the groups. There was, however, a significant decrease in both the days of maternal hospitalization and maternal hospital expenses in the home group.\n Only a very small proportion of cases of preterm PROM (18%) could meet the strict safety criteria for inclusion used in the study. In the home-management group, length of the latency period and gestational age at delivery were not significantly different than in hospitalized patients." ]

[ "11248591" ]

[ "Levodopa or dopamine agonists, or deprenyl as initial treatment for Parkinson's disease. A randomized multicenter study." ]

[ "Objectives: levodopa improves the quality of life in parkinsonian patients, however long term response is compromised by the emergence of motor fluctuations and dyskinesias. The aim of this study was to compare the occurrence of motor fluctuations and dyskinesias in previously untreated patients assigned to receive levodopa, a dopamine agonist or deprenyl.Thirty-five neurological departments in Italian hospitals participated in this randomized open trial. Patients with Parkinson's disease, who required the initiation of an effective antiparkinsonian treatment, were randomly assigned to receive levodopa, dopamine agonists or deprenyl. The end-points were motor dyskinesias and motor fluctuations occurring in a median follow-up period of about 3years.After a median follow-up of 34months, motor fluctuations and dyskinesias were less frequent in patients assigned to a dopamine agonist or deprenyl than in patients assigned to levodopa (relative risk [RR] 0.5, 95% confidence interval [95% CI] 0.3-0.8, and RR=0.6, 95% CI 0.3-0.9, respectively), but dopamine agonists were less effective and less well tolerated than levodopa. The lower frequency of motor fluctuations in patients assigned to deprenyl was no longer statistically significant when prognostic predictors were considered in a multivariable analysis. Long-term mortality did not differ in the three arms of the study. Dopamine agonists and deprenyl can be considered as an alternative to levodopa for starting treatment in Parkinson's disease patients. However, on clinical grounds, only small advantages are expected over the traditional therapy initiation with levodopa." ]

[ "1872778" ]

[ "Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia." ]

[ "A series of 45 ovulatory women with a complaint of menorrhagia were randomized into 3 treatment groups, before receiving therapy with mefenamic acid in 2 cycles and 1 of 3 other agents in 2 cycles: naproxen (group 1; n = 14), a low dose monophasic combined oral contraceptive (group 2; n = 12) or low dose danazol (group 3; n = 12). Menstrual blood loss was measured in 2-4 control cycles and during therapy. Mefenamic acid reduced measured blood loss by 20%; 38%; and 39% in groups 1-3 respectively. Naproxen reduced blood loss by 12%; the oral contraceptive by 43%; and danazol by 49%. There was no statistically significant difference in blood loss reduction (mean of 2 cycles) between any of the treatments, although women on danazol experienced a dramatic and highly significant further reduction in blood loss after the first treatment cycle (p less than 0.003). These were all effective therapies in a majority of women, but some 'non-responders' were seen in each group. The 'non-responders' had a significantly lower pretreatment blood loss than responders. Several women in group 1 showed anomalous responses to prostaglandin inhibitors with consistent and substantial exacerbation of menorrhagia during therapy. A number of reasonable therapies exist for the medical treatment of menorrhagia, but because none is suitable for everyone management needs to be individualized for each patient." ]

[ "15698593", "12145004", "1484945", "12756385", "15624283", "11395029", "8650428", "15330272", "7595101", "1516292" ]

[ "Non-cholesterol sterols in serum, lipoproteins, and red cells in statin-treated FH subjects off and on plant stanol and sterol ester spreads.", "Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia.", "Dietary management of patients with familial hypercholesterolaemia treated with simvastatin.", "Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia.", "Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study.", "Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread.", "Fish oil supplementation in patients with heterozygous familial hypercholesterolemia.", "Comparison of the effects of dietary plant sterol and stanol esters on lipid metabolism.", "Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia.", "High protein diet complements resin therapy of familial hypercholesterolemia." ]

[ "Serum plant sterol levels are increased by consumption of statins and dietary plant sterols, and decreased by dietary plant stanols, but little is known about combination therapy of statin and plant sterols.\n We measured plant sterols in serum, lipoproteins, and red cells in subjects with familial hypercholesterolemia (FH) (n=18) treated with variable doses of statins off and on plant stanol (STA) and sterol ester (STE) spreads.\n STA and STE spreads lowered LDL cholesterol approximately 15%. Plant sterols were decreased in serum, lipoproteins, and red cells by approximately 25% with STA and increased from 37% to 80% with STE, especially with high statin doses. The changes in serum were related to those in red cells. The baseline levels of serum plant sterols were negatively (r-range -0.639 to -0.935) and positively (r-range 0.526 to 0.598) correlated with the respective changes evoked by the STA and STE spreads.\n STE reduces LDL cholesterol, but increases serum, lipoprotein, and red cell plant sterol levels in statin-treated FH subjects, while all the respective values are decreased with STA. Recent predictions that elevated serum plant sterols pose an increased coronary risk suggest that increases of serum plant sterol levels should be avoided, especially in atherosclerosis-prone individuals, such as subjects with FH.", "Naturally occurring plant sterol esters (SEs) favorably affect serum cholesterol concentrations in humans and could aid in the treatment of children with familial hypercholesterolemia (FH).\n We studied the effect of SE-enriched spread on serum lipids, lipoproteins, carotenoids, fat-soluble vitamins, and physiologic variables in children with FH aged 7-12 y.\n In a randomized, double-blind crossover study comprising two 8-wk interventions, 38 children with FH consumed 18.2 +/- 1.5 g SE spread/d, corresponding to 1.60 +/- 0.13 g SEs, or a control spread. Blood samples were analyzed at the start and end of each diet period.\n Plasma LDL-cholesterol concentrations decreased by 10.2% (P = 0.003) during the SE period compared with the control period. Total cholesterol and apolipoprotein B concentrations were reduced by 7.4% (P = 0.007 and P = 0.020, respectively) during the SE period. No changes were observed in HDL cholesterol, triacylglycerol, or apolipoprotein A-I. Serum concentration of lipid-adjusted lycopene decreased by 8.1% (P = 0.015) in the SE period, with no changes in the other carotenoids. Lipid-adjusted retinol and alpha-tocopherol concentrations increased by 15.6% (P < 0.001) and 7.1% (P = 0.027), respectively. There was an increase (16.8%, P = 0.04) in alanine transaminase in the SE period, but this was explained by a significantly lower starting concentration in the SE period than in the control period. The children consumed a recommended American Heart Association Step I diet during both intervention periods.\n A daily intake of 1.6 g SEs induces an additional reduction in LDL-cholesterol concentrations in children with FH consuming a recommended diet.", "The effect of diet on plasma lipids and lipoproteins was examined in 19 patients with familial hypercholesterolaemia treated with the HMGCoA reductase inhibitor, simvastatin. The study was a randomized double-blind cross-over trial of two diets: a low fat diet and a higher fat diet, and was performed to determine whether ongoing attention to diet is necessary for patients receiving this drug for the treatment of familial hypercholesterolaemia. Plasma cholesterol concentration was 6.5 per cent lower on the low fat diet than on the high fat diet. The difference was within the range predicted by the Jacobs modification of the Keys formula from the reported intake on the two diets. The fall on the low fat diet was principally accounted for by a reduction in low density lipoprotein cholesterol, although high density lipoprotein cholesterol and apolipoprotein A1 also fell. Patients taking HMGCoA reductase inhibitors for the treatment of familial hypercholesterolaemia respond to changes in dietary fat intake. They are thus likely to achieve further reduction in their coronary heart disease risk, and should remain on a low saturated fat low cholesterol diet even when taking these powerful lipid lowering drugs.", "To show whether the ratios of squalene and cholesterol precursor sterols to cholesterol and cholestanol and plant sterols to cholesterol change differently in plasma and especially in the red cells of hypercholesterolemic children during consumption of plant stanol and sterol ester spreads.\n In a randomized, double-blind, crossover study, hypercholesterolemic children (n = 23) consumed low-fat plant stanol and sterol ester spreads for 5-week periods separated by a 5-week washout period. Plasma and red cell lipids, squalene, and noncholesterol sterols were measured before and at the end of each period.\n The plant stanol and sterol ester spreads lowered plasma total (-9% and -6%, respectively) and low-density lipoprotein (-12% and -9%) cholesterol but had no effect on red cell cholesterol, high-density lipoprotein cholesterol, or plasma triglycerides. The ratios of plasma and red cell sitosterol and campesterol to cholesterol decreased by 32% to 36% (P <.001) with the plant stanol ester and increased by 40% to 52% (P <.001) with the sterol ester spread.\n Consumption of plant sterols increases and consumption of plant stanols decreases the ratios of plant sterols to cholesterol in red cells of hypercholesterolemic children proportionately to the respective changes in plasma.", "The primary objective of this study was to determine whether the National Cholesterol Education Program Step II (NCEP-II) diet or supplementation with docosahexaenoic acid (DHA) with the diet, affects endothelial function in children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). As secondary endpoints, the influence of diet and DHA supplementation on lipid profiles as well as biomarkers for oxidative stress and inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, were all evaluated.\n In a double-blind, placebo-controlled, randomized, crossover study design, 20 children (ages 9-19 years) with FH (n = 12) and FCH (n = 8) received nutritional counseling based on the National Cholesterol Education Program Step II (NCEP-II) and food guide pyramid dietary guidelines for 6 weeks. They were then randomly assigned to supplementation with docosahexaenoic acid (DHA 1.2 g/d) or placebo for 6 weeks, followed by a washout phase of 6 weeks and crossover phase of 6 weeks while continuing the NCEP-II diet. Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was determined by high-resolution ultrasound. Plasma levels of total cholesterol, triglycerides and lipoprotein classes (LDL, HDL, VLDL) were measured by ultracentrifugation and enzymatic methods, plasma F2 isoprostanes by gas chromatography/mass spectrometry, urinary 8-OH-2' deoxyguanosine by liquid chromatography, high sensitivity C-reactive protein by immunonephelometry and ADMA by liquid chromatography.\n FMD increased significantly after DHA supplementation compared to baseline (p < 0.001), diet alone (p < 0.002), placebo (p < 0.012) and washout (p < 0.001) phases of the study without affecting biomarkers for oxidative stress, inflammation or ADMA. DHA supplementation was associated with increased levels of total cholesterol (p < 0.01), LDL- and HDL cholesterol concentrations (p < 0.001) compared to the NCEP-II diet.\n This study demonstrates that DHA supplementation restores endothelial-dependent FMD in hyperlipidemic children. The endothelium may thus be a therapeutic target for DHA. This is consistent with a hypothesis of increasing NO bioavailability, with the potential for preventing the progression of early coronary heart disease in high-risk children.", "Plant sterols may be a useful additive therapy in the treatment of hypercholesterolaemic patients. The purpose of this study was to determine the effect of a fat spread enriched with vegetable oil sterols on plasma lipid, lipoprotein and apolipoprotein concentrations. A randomised double blind placebo-controlled crossover trial with two consecutive periods of 8 weeks was conducted. 30 patients with heterozygous familial hypercholesterolaemia treated concurrently with an HMG-CoA reductase inhibitor (statin) and 32 patients with type IIa primary hypercholesterolaemia with a total cholesterol concentration >6.5 mmol/l not taking lipid-lowering drug therapy were recruited from a hospital lipid clinic. The active treatment was a fortified fat spread (25 g/day) providing 2.5 g of plant sterols. The control spread was indistinguishable in taste and appearance. Comparison at the end of the two 8-week trial periods showed a statistically significant reduction in total and LDL-cholesterol with use of the fortified spread but the results were confounded by a carry-over effect, which was partly explained by changes in the background diet. Because a carry-over effect was present, further analyses were restricted to the parallel arms of the first treatment period and were conducted on an intention to treat basis. After 4 weeks, LDL-cholesterol had decreased by 0.04 mmol/l ([0.8%] 95% confidence interval -0.44-0.37 NS) in the placebo group and decreased by -0.76 mmol/l ([15.0%] 95% CI -1.03--0.48, P<0.0001) in the active treatment group. After 8 weeks, the corresponding results were 0.0 mmol/l ([0.0%] 95% CI -0.26-0.24 NS) and -0.51 mmol/l ([10.0%] 95% CI -0.73--0.29 P<0.0001). There were no significant changes in apolipoprotein AI or B concentrations in the placebo group, but there was a small but statistically significant increase in apolipoprotein AI and a decrease in apolipoprotein B in the active treatment group. HDL cholesterol and triglyceride concentrations were unchanged. There was no difference in response between patients with statin-treated familial hypercholesterolaemia and patients with type IIa hyperlipoproteinaemia. We conclude that a fortified fat spread enriched with vegetable oil sterols reduces LDL-cholesterol by 10-15% with no difference in response between hypercholesterolaemic patients prescribed statins and those not taking lipid-lowering drug therapy.", "Familial hypercholesterolemia is associated with premature coronary heart disease. In patients with familial hypercholesterolemia, monotherapy with hydroxymethylglutaril coenzyme. A reductase inhibitors rarely achieves the goal of desirable low-density lipoprotein levels. Epidemiological studies suggest that populations with a high dietary intake of marine n3 fatty acids are protected against coronary heart disease. Hepatic synthesis and secretion of very low density lipoproteins are reduced during fish oil supplementation while other effects on lipid and lipoprotein metabolism are controversial. Fourteen patients affected by familial heterozygous hypercholesterolemia on chronic treatment with simvastatin were enrolled in a double blind, placebo controlled, randomized crossover trial that evaluated the effect of fish oil ethyl ester (Esapent, 5.1 g/day) on lipid and lipoprotein serum concentrations. Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apoprotein B, apoprotein AI, lipoprotein (a) did not show any significant variation during the four week treatment period with fish oil ethyl ester. The present data suggest that the possible favourable influence of fish oil on the progression of atherosclerosis in these high-risk patients might involve mechanisms which are different from lipid metabolism.", "To compare the cholesterol-lowering efficacy and other metabolic effects of plant sterol and stanol esters, both of which are commonly used in the dietary management of hypercholesterolaemia.\n The cholesterol-lowering efficacy of equivalent intakes of sterol and stanol esters and of different intakes of stanol esters were compared at 1 and 2 months, both in normal subjects and treated patients with familial hypercholesterolaemia. Systemic effects were assessed by measuring serum levels of plant sterols and of lathosterol and 7alpha-hydroxy-cholestenone, indices of sterol absorption and of cholesterol and bile acid synthesis respectively. There were no significant differences during the study between 1.6g daily of sterol and stanol esters in reducing total cholesterol (by 3-7%) or low density lipoprotein cholesterol (by 4-8%), nor between 1.6 and 2.6 g daily of stanol. However, the cholesterol-lowering effect of plant sterol esters was attenuated between 1 and 2 months. This was accompanied by increased serum plant sterols and decreased levels of 7alpha-hydroxy-cholestenone, especially in statin-treated hypercholesterolaemic patients not taking bile acid sequestrants.\n These findings suggest that absorption of dietary plant sterols suppressed bile acid synthesis, thereby diminishing their cholesterol-lowering efficacy. In contrast, plant stanols reduced plant sterol absorption and maintained their cholesterol-lowering efficacy.", "In familial hypercholesterolemia (FH) the lowering of serum cholesterol levels should be started in childhood in order to prevent coronary artery disease later in life. However, treatment of children is problematic. We studied the effects of sitostanol (3 g/day) ester dissolved in rapeseed oil margarine as a hypocholesterolemic agent in one homozygous and 14 heterozygous children with FH maintained on a low cholesterol diet for 6 weeks, using a double-blind crossover design. Absorption and synthesis of cholesterol were evaluated by measuring serum plant sterol and cholesterol precursor proportions to cholesterol by gas-liquid chromatography. The compliance was good, and the children could not distinguish by taste the two margarines without and with sitostanol ester. Sitostanol margarine significantly reduced serum total, intermediate density (IDL), and low density lipoprotein (LDL) cholesterol by 11, 26, and 15%, respectively, and increased HDL/LDL cholesterol ratio by 27%. The proportions of serum delta 8-cholestenol, lathosterol, and desmosterol were significantly increased by 36, 19, and 18%, and those of serum cholestanol, campesterol, and sitosterol were significantly decreased by 9, 42 and 29%, respectively, suggesting that cholesterol absorption was decreased and synthesis was compensatorily increased. High basal precursor sterol proportions predicted a high decrease in LDL cholesterol levels. In conclusion, partial replacement of normal dietary fat consumption by sitostanol ester margarine appears to be an effective and safe hypocholesterolemic treatment in children with FH.", "The intermediate-term effects on plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of five subjects (three women, two men) with familial hypercholesterolemia receiving cholestyramine (mean dose, 18 g/d) were studied. Subjects were randomly allocated to either the high or low protein diets (mean 27 versus 10% of energy as protein, 25% as fat, and 48 versus 65% as carbohydrate) for 4 to 5 weeks and then switched to the other diet for another 4 to 5 weeks. Mean fasting plasma HDL cholesterol rose significantly by 17 +/- 3% (1.11 +/- 0.12 vs 0.95 +/- 0.11 mmol/L, p less than 0.005, n = 5), whereas total triglycerides fell by 23 +/- 2% (1.7 +/- 0.3 vs 2.2 +/- 0.3 mmol/L, p less than 0.005, n = 5), VLDL triglycerides fell by 28 +/- 5% (0.88 +/- 0.15 vs 1.18 +/- 0.19 mmol/L, p less than 0.02, n = 5), VLDL cholesterol fell by 32 +/- 7% (0.39 +/- 0.08 vs 0.56 +/- 0.09 mmol/L, p less than 0.01, n = 5), the ratio of LDL cholesterol: HDL cholesterol by 19 +/- 5% (4.7 +/- 0.7 vs 5.7 +/- 0.7, p less than 0.05) and that of total cholesterol: HDL cholesterol by 16 +/- 5% (6.6 +/- 0.5 vs 8.0 +/- 0.7, p less than 0.05) on the high versus low protein diet. Increasing dietary protein intake at the expense of carbohydrate may be useful in treating hypoalphalipoproteinemia and/or hypertriglyceridemia in patients with familial hypercholesterolemia." ]

[ "19506159", "22877848", "15800329", "10735896", "19016015", "22578793", "20855843", "15758009" ]

[ "Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma.", "Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial.", "Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme.", "Health-related quality of life in patients treated with temozolomide versus procarbazine for recurrent glioblastoma multiforme.", "Randomized study of postoperative radiotherapy and simultaneous temozolomide without adjuvant chemotherapy for glioblastoma.", "Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial.", "Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma.", "Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma." ]

[ "Alternative dosing schedules of temozolomide may improve survival in patients with newly diagnosed glioblastoma (GBM) by increasing the therapeutic index, overcoming common mechanisms of temozolomide resistance, or both. The goal of this randomized phase II study was to evaluate two different temozolomide regimens in the adjuvant treatment of newly diagnosed GBM.\n Adult patients with newly diagnosed GBM were randomly assigned to receive standard radiotherapy with concurrent daily temozolomide followed by six adjuvant cycles of either dose-dense (150 mg/m(2) days 1 to 7 and 15 to 21) or metronomic (50 mg/m(2) continuous daily) temozolomide. Maintenance doses of 13-cis-retinoic acid were then administered until tumor progression. The primary end point was overall survival (OS) at 1 year. Tumor tissue was assayed to determine O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status.\n Eighty-five eligible patients were enrolled; 42 were randomly assigned to dose-dense and 43 to metronomic temozolomide. The 1-year survival rate was 80% for the dose-dense arm and 69% for the metronomic arm; median OS was 17.1 months (95% CI, 14.0 to 28.1 months) and 15.1 months (95% CI, 12.3 to 18.9 months), respectively. The most common toxicities were myelosuppression (leukopenia, neutropenia, and thrombocytopenia) and elevated liver enzymes. Pseudoprogression was observed in 37% of assessable patients and may have had an impact on estimates of progression-free survival (6.6 months in the dose-dense arm and 5.0 months in the metronomic arm).\n Both dose-dense and metronomic temozolomide regimens were well tolerated with modest toxicity. The dose-dense regimen appears promising, with 1-year survival of 80%.", "Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma.\n Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34·0 Gy administered in 3·4 Gy fractions over 2 weeks), or standard radiotherapy (60·0 Gy administered in 2·0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623.\n 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8·3 months [95% CI 7·1-9·5; n=93] vs 6·0 months [95% CI 5·1-6·8; n=100], hazard ratio [HR] 0·70; 95% CI 0·52-0·93, p=0·01), but not with hypofractionated radiotherapy (7·5 months [6·5-8·6; n=98], HR 0·85 [0·64-1·12], p=0·24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8·4 months [7·3-9·4; n=119] vs 7·4 months [6·4-8·4; n=123]; HR 0·82, 95% CI 0·63-1·06; p=0·12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0·35 [0·21-0·56], p<0·0001; HR for hypofractionated vs standard radiotherapy 0·59 [95% CI 0·37-0·93], p=0·02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9·7 months [95% CI 8·0-11·4] vs 6·8 months [5·9-7·7]; HR 0·56 [95% CI 0·34-0·93], p=0·02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0·97 [95% CI 0·69-1·38]; p=0·81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed.\n Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.\n Merck, Lion's Cancer Research Foundation, University of Umeå, and the Swedish Cancer Society.\n Copyright © 2012 Elsevier Ltd. All rights reserved.", "Surgery remains the standard treatment for glioma, followed by radiotherapy (RT) with or without chemotherapy. Despite multidisciplinary approaches, the median survival time for patients with glioblastoma multiform (GBM) remains at less than 1 year from initial diagnosis. Temozolomide (TMZ), an oral alkylating agent, has shown promising activity in the treatment of malignant gliomas. We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM.\n One hundred thirty patients with pathologically confirmed, newly diagnosed GBM were randomly assigned (110 assessable patients) to receive either TMZ 75 mg/m(2)/d orally, concomitantly with RT (60 Gy in 30 fractions; group A, n = 57), followed by six cycles of TMZ (150 mg/m(2) on days 1 through 5 and 15 to 19 every 28 days), or RT alone (60 Gy in 30 fractions; group B, n = 53).\n Median time to progression was 10.8 months in group A and 5.2 months in group B (P = .0001). One-year progression-free survival rate was 36.6% in group A and 7.7% in group B. Median overall survival (OS) time was also significantly better in group A versus group B (13.4 v 7.7 months, respectively; P < .0001), as was the 1-year OS at 56.3% v 15.7% (P < .0001), respectively. Toxicity was mainly hematologic. One patient with grade 4 myelotoxicity died as a result of sepsis. The other side effects were mild.\n TMZ combined with RT (concomitantly and sequentially) seems to be more effective than RT alone in patients with newly diagnosed GBM. The combined-modality treatment was well tolerated.", "To determine whether chemotherapy with temozolomide (TMZ) versus procarbazine (PCB) for recurrent glioblastoma multiforme (GBM) was associated with improvement in health-related quality of life (HRQOL).\n HRQOL was assessed at baseline and during treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and a Brain Cancer Module (BCM20) in two clinical trials that enrolled a total of 366 patients. Two hundred eighty-eight patients provided HRQOL data that could be used for analysis; 109 patients received TMZ in a phase II study, whereas 89 patients received TMZ and 90 received PCB in a randomized phase III study. Changes from baseline in the scores of seven preselected HRQOL domains (role and social functioning, global quality of life [QOL], visual disorders, motor dysfunction, communication deficit, and drowsiness) were calculated for all groups. Statistical significance, effect sizes, and proportions of patients with improved HRQOL scores (changes of > or = 10 points) were calculated.\n Before disease progression, patients treated with TMZ were found to have an improvement in most of the preselected HRQOL domain scores compared with their baseline (pretreatment) scores. Those who were progression-free on TMZ at 6 months had improvement in all the preselected HRQOL domains. Conversely, patients treated with PCB reported deterioration in HRQOL that was independent of whether or not the disease had progressed by 6 months. Patients with disease progression, regardless of treatment, experienced a sharp decline in all domains at the time of progression.\n Treatment with TMZ was associated with improvement in HRQOL scores compared with treatment with PCB. The deterioration reported by PCB-treated patients was likely because of toxicity. Delaying disease progression by treatment with TMZ is beneficial to the HRQOL status of patients with recurrent GBM.", "To evaluate the efficacy of simultaneous postoperative temozolomide radiochemotherapy in glioblastoma patients.\n From February 2002 to July 2004, n = 65 patients from 11 German centers with macroscopic complete tumor resection were randomized to receive either postoperative radiotherapy alone (RT, n = 35) or postoperative radiotherapy with simultaneous temozolomide (RT + TMZ, n = 30). Patients were stratified according to age (< or =/>50 years) and WHO performance score (0-1 vs. 2). RT consisted of 60 Gy in 30 fractions. In the RT + TMZ arm, oral TMZ was administered daily at a dose of 75 mg/m(2) including weekends (40-42 doses). Adjuvant treatment was not given, but in both arms, patients with recurrent tumors and in good condition (WHO 0-2) were scheduled for salvage chemotherapy with TMZ.\n The trial was stopped early due to the results of EORTC-study 26981-22981 that showed a survival benefit for the combination of concomitant and adjuvant TMZ compared to radiotherapy alone. In total, 62/65 patients were evaluable. Stratification variables were well balanced (< or = 50 years 26% vs. 20%, WHO 0-1 91% vs. 100%). Neither overall survival (median 17 vs. 15 months) nor progression-free survival (median 7 vs. 6 months) differed significantly between the two arms. In the RT (RT + TMZ) arm, 76% (62%) of the progressing patients received salvage chemotherapy with TMZ, 36% (50%) had a second resection. There was a time-constant trend for increased general quality of life (EORTC questionnaire QLQ C30) and brain-specific quality of life (EORTC questionnaire B20) in the combined arm. Lymphopenia G3-4 was more frequent (33 vs. 6%) in the RT + TMZ arm.\n After early closure of this trial, a benefit for progression-free survival for simultaneous TMZ radiochemotherapy alone could not be demonstrated. In both arms, salvage therapies were frequently used and probably had a major effect on overall survival.", "Radiotherapy is the standard care in elderly patients with malignant astrocytoma and the role of primary chemotherapy is poorly defined. We did a randomised trial to compare the efficacy and safety of dose-dense temozolomide alone versus radiotherapy alone in elderly patients with anaplastic astrocytoma or glioblastoma.\n Between May 15, 2005, and Nov 2, 2009, we enrolled patients with confirmed anaplastic astrocytoma or glioblastoma, age older than 65 years, and a Karnofsky performance score of 60 or higher. Patients were randomly assigned 100 mg/m(2) temozolomide, given on days 1-7 of 1 week on, 1 week off cycles, or radiotherapy of 60·0 Gy, administered over 6-7 weeks in 30 fractions of 1·8-2·0 Gy. The primary endpoint was overall survival. We assessed non-inferiority with a 25% margin, analysed for all patients who received at least one dose of assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01502241.\n Of 584 patients screened, we enrolled 412. 373 patients (195 randomly allocated to the temozolomide group and 178 to the radiotherapy group) received at least one dose of treatment and were included in efficacy analyses. Median overall survival was 8·6 months (95% CI 7·3-10·2) in the temozolomide group versus 9·6 months (8·2-10·8) in the radiotherapy group (hazard ratio [HR] 1·09, 95% CI 0·84-1·42, p(non-inferiority)=0·033). Median event-free survival (EFS) did not differ significantly between the temozolomide and radiotherapy groups (3·3 months [95% CI 3·2-4·1] vs 4·7 [4·2-5·2]; HR 1·15, 95% CI 0·92-1·43, p(non-inferiority)=0·043). Tumour MGMT promoter methylation was seen in 73 (35%) of 209 patients tested. MGMT promoter methylation was associated with longer overall survival than was unmethylated status (11·9 months [95% CI 9·0 to not reached] vs 8·2 months [7·0-10·0]; HR 0·62, 95% CI 0·42-0·91, p=0·014). EFS was longer in patients with MGMT promoter methylation who received temozolomide than in those who underwent radiotherapy (8·4 months [95e% CI 5·5-11·7] vs 4·6 [4·2-5·0]), whereas the opposite was true for patients with no methylation of the MGMT promoter (3·3 months [3·0-3·5] vs 4·6 months [3·7-6·3]). The most frequent grade 3-4 intervention-related adverse events were neutropenia (16 patients in the temozolomide group vs two in the radiotherapy group), lymphocytopenia (46 vs one), thrombocytopenia (14 vs four), raised liver-enzyme concentrations (30 vs 16), infections (35 vs 23), and thromboembolic events (24 vs eight).\n Temozolomide alone is non-inferior to radiotherapy alone in the treatment of elderly patients with malignant astrocytoma. MGMT promoter methylation seems to be a useful biomarker for outcomes by treatment and could aid decision-making.\n Merck Sharp & Dohme.\n Copyright © 2012 Elsevier Ltd. All rights reserved.", "Temozolomide (TMZ) is an alkylating agent licensed for treatment of high-grade glioma (HGG). No prospective comparison with nitrosourea-based chemotherapy exists. We report, to our knowledge, the first randomized trial of procarbazine, lomustine, and vincristine (PCV) versus TMZ in chemotherapy-naive patients with recurrent HGG.\n Four hundred forty-seven patients were randomly assigned to PCV (224 patients) or TMZ (sub-random assignment: TMZ-5 [200 mg/m(2) for 5 days, 112 patients] or TMZ-21 [100 mg/m(2) for 21 days, 111 patients]) for up to 9 months or until progression. The primary outcomes were survival (PCV v TMZ) and 12-week progression-free survival (PFS; TMZ-5 v TMZ-21). This study is registered as ISRCTN83176944.\n Percentages of patients completing 9 months of treatment in the PCV, TMZ-5, and TMZ-21 arms were 17%, 26%, and 13%, respectively. Major toxicity was similar across all three groups. With a median follow-up time of 12 months and 382 deaths, there was no clear survival benefit when comparing PCV with TMZ (hazard ratio [HR], 0.91; 95% CI, 0.74 to 1.11; P = .350). For TMZ-5 versus TMZ-21, 12-week PFS rates were similar (63.6% and 65.7%, respectively; P = .745), but TMZ-5 improved overall PFS (HR, 1.38; 95% CI, 1.05 to 1.82; P = .023), survival (HR, 1.32; 95% CI, 0.99 to 1.75; P = .056), and global quality of life (49% v 19% improved > 10 points at 6 months, respectively; P = .005).\n Although TMZ (both arms combined) did not show a clear benefit compared with PCV, comparison of the TMZ schedules demonstrated that the 21-day schedule was inferior to the 5-day schedule in this setting. This challenges the current understanding of increasing TMZ dose-intensity by prolonged scheduling.", "Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety.\n Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival.\n A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients.\n The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.\n Copyright 2005 Massachusetts Medical Society." ]

[ "10631825" ]

[ "Use of castor oil in pregnancies at term." ]

[ "Despite wide use of castor oil to initiate labor, the obstetric literature contains few references to this botanical laxative. Derived from the castor plant Ricinus communis, castor oil may possess properties that are useful in post-term pregnancies.\n To evaluate the relationship between the use of castor oil and the onset of labor.\n Prospective evaluation.\n A community hospital in Brooklyn, NY.\n A total of 103 singleton pregnancies with intact membranes at 40 to 42 weeks referred for antepartum testing. Inclusion criteria included cervical examination, Bishop score of 4 or less, and no evidence of regular uterine contractions.\n Patients were alternately assigned to 1 of 2 study groups: a single oral dose of castor oil (60 mL) or no treatment.\n Castor oil was considered successful if labor began within 24 hours after dosing. Groups were compared for onset of labor in 24 hours, method of delivery, presence of meconium-stained amniotic fluid, Apgar score, and birth weight.\n Fifty-two women received castor oil and 48 were assigned no treatment. Following administration of castor oil, 30 of 52 women (57.7%) began active labor compared to 2 of 48 (4.2%) receiving no treatment. When castor oil was successful, 83.3% (25/30) of the women delivered vaginally.\n Women who receive castor oil have an increased likelihood of initiation of labor within 24 hours compared to women who receive no treatment. Castor oil use in pregnancy is underreported worldwide. This small series represents the first attempt to evaluate the medication." ]

[ "10615885", "8495772", "19531445", "15044399" ]

[ "Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost-effectiveness analysis.", "A randomized trial of in vitro fertilization versus conventional treatment for infertility.", "A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial.", "A multicentre randomized controlled trial of expectant management versus IVF in women with Fallopian tube patency." ]

[ "Couples affected by idiopathic subfertility or male subfertility have an estimated spontaneous conception rate of about 2% per cycle. Although various infertility treatments are available, counselling of a couple in their choice of treatment is difficult because of the lack of consistent data from good-quality comparative studies. We compared the results of treatment with intrauterine insemination (IUI) with those of in-vitro fertilisation (IVF), and did a cost-effectiveness analysis.\n In a prospective, randomised, parallel trial, 258 couples with idiopathic subfertility or male subfertility were treated for a maximum of six cycles of either IUI in the spontaneous cycle (IUI alone), IUI after mild ovarian hyperstimulation, or IVF. The primary endpoint was a pregnancy resulting in at least one livebirth after treatment. Cost-effectiveness based on real costs was studied by Markov chain analysis.\n 86 couples were assigned IUI alone, 85 IUI plus ovarian hyperstimulation, and 87 IVF. Ten couples dropped out before treatment began. Although the pregnancy rate per cycle was higher in the IVF group than in the IUI groups (12.2% vs 7.4% and 8.7%, respectively; p=0.09), the cumulative pregnancy rate for IVF was not significantly better than that for IUI. Couples in the IVF group were more likely than those in the IUI groups to give up treatment before their maximum of six attempts (37 [42%] drop-outs vs 13 [15%] and 14 [16%], respectively; p<0.01). The woman's age was the only factor that influenced a couple's chance of success. IUI was a more cost-effective treatment than IVF (costs per pregnancy resulting in at least one livebirth 8423-10661 Dutch guilders [US$4511-5710] for IUI vs 27409 Dutch guilders [US$14679] for IVF).\n Couples with idiopathic or male subfertility should be counselled that IUI offers the same likelihood of successful pregnancy as IVF, and is a more cost-effective approach. IUI in the spontaneous cycle carries fewer health risks than does IUI after mild hormonal stimulation and is therefore the first-choice treatment.", "To evaluate the effectiveness of IVF in couples with infertility.\n Two hundred forty-five consecutive couples with infertility were randomized to receive one cycle of IVF treatment (experimental group) or to wait for a period of 6 months before receiving IVF treatment, during which time other infertility treatments could have been undertaken (control group).\n Patients were referred to the Fertility Clinic at Chedoke-McMaster Hospitals, a university-associated institution in Hamilton, Ontario, Canada, in which IVF has been offered to couples since 1984.\n Couples with infertility (mean duration of 65 months) not corrected by conventional treatment. They came from all socioeconomic classes, and the costs of IVF treatment, except medication, were covered by the Ontario Health Insurance Plan.\n Pregnancy was confirmed by ultrasound documentation of a gestational sac or histologic examination of tissue. Outcomes included livebirth, spontaneous abortion, and ectopic pregnancy. The overall pregnancy rate (PR) and the interval-to-pregnancy duration were compared in each group.\n Univariate analysis demonstrated a significant beneficial effect of IVF treatment in patients with bilateral severe tubal disease. Although in other diagnostic categories the crude and cumulative PRs in the experimental group were higher than in the control group, the differences did not reach statistical significance. Among the early IVF group, those with endometriosis had significantly more pregnancies when compared with other diagnostic categories. Although IVF increases the likelihood of pregnancy by 40% with severe tubal disease, the overall 31% increase associated with IVF was not statistically significant.\n There was a significant difference in favor of treatment in patients with severe bilateral tubal disease. For couples with other causes of infertility, the confidence limits around the treatment effect included unity. To reject the null hypothesis of no treatment effect, a larger sample size or a meta-analysis to combine the results of similar trials is required.", "To determine the value of gonadotropin/intrauterine insemination (FSH/IUI) therapy for infertile women aged 21-39 years.\n Randomized controlled trial.\n Academic medical center associated with a private infertility center.\n Couples with unexplained infertility.\n Couples were randomized to receive either conventional treatment (n=247) with three cycles of clomiphene citrate (CC)/IUI, three cycles of FSH/IUI, and up to six cycles of IVF or an accelerated treatment (n=256) that omitted the three cycles of FSH/IUI.\n The time it took to establish a pregnancy that led to a live birth and cost-effectiveness, defined as the ratio of the sum of all health insurance charges between randomization and delivery divided by the number of couples delivering at least one live-born baby.\n An increased rate of pregnancy was observed in the accelerated arm (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.00-1.56) compared with the conventional arm. Median time to pregnancy was 8 and 11 months in the accelerated and conventional arms, respectively. Per cycle pregnancy rates for CC/IUI, FSH/IUI, and IVF were 7.6%, 9.8%, and 30.7%, respectively. Average charges per delivery were $9,800 lower (95% CI, $25,100 lower to $3,900 higher) in the accelerated arm compared to conventional treatment. The observed incremental difference was a savings of $2,624 per couple for accelerated treatment and 0.06 more deliveries.\n A randomized clinical trial demonstrated that FSH/IUI treatment was of no added value.\n Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "Although observational studies suggest that IVF is more effective than no treatment for women with Fallopian tube patency, this has not been tested rigorously in a randomized controlled trial (RCT).\n Eligible consenting couples planning their first treatment cycle in five Canadian fertility clinics received either IVF, within 90 days of randomization, or a period of 90 days with no treatment. Random allocation was stratified by female age and sperm quality, and administered using numbered, opaque, sealed envelopes. Follow-up assessed live birth and associated morbidity.\n Sixty-eight couples were randomized to a first cycle of IVF and 71 couples had 3 months without treatment. The live birth rates were 20/68 (29%) and 1/71 (1%), respectively. The single delivery in the untreated group was of twins, as were six of the 20 IVF deliveries (30%). An average of 2.0 embryos were transferred and no triplet pregnancies resulted. The relative likelihood of delivery after allocation to IVF was 20.9-fold higher than after allocation to no treatment [95% confidence interval (CI) 2.8-155]. The presence of abnormal sperm did not reduce this likelihood. Treating four women (95% CI 3-6) with one cycle of IVF is required to achieve a single additional birth.\n This study provides a valid and up-to-date comparison for policy makers and patients as they make choices around IVF, accurately measuring and confirming a major benefit from treatment." ]

[ "20559821" ]

[ "The acute effects of glucose ingestion on attentional control in fasting healthy older adults." ]

[ "Glucose enhancing effects have been observed in older adults mainly for episodic memory, but have been under-investigated for attentional functions, which are very sensitive to aging.\n The present study examined the acute effects of glucose ingestion on different attentional tasks in fasting healthy older adults.\n In a between-subjects design, 44 participants (60 years and older) were randomly assigned to a glucose (50 g) or saccharin (placebo) condition after 12 h of fasting. Participants were tested on neuropsychological tests of attention (trail A and B, modified Stroop) and on a computerized dual-task.\n Participants in the glucose group were faster than the placebo group to complete the switching condition of the modified Stroop test (p < 0.01) and showed a smaller dual-task cost in the divided attention task (p < 0.05).\n Glucose ingestion appears to momentarily enhance attentional performances in seniors who have fasted for 12 h in tasks requiring switching and dividing attention." ]

[ "14601905", "1365692", "1455880", "7518020", "11783101", "9869669", "11391598", "9270638", "2456424" ]

[ "Prospective evaluation of preoperative chemotherapy in resectable squamous cell carcinoma of the thoracic esophagus.", "Randomized trial of preoperative chemotherapy for squamous cell cancer of the esophagus. The Chirurgische Arbeitsgemeinschaft Fuer Onkologie der Deutschen Gesellschaft Fuer Chirurgie Study Group.", "Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer.", "Induction chemotherapy in the treatment of patients with carcinoma of the esophagus.", "[A randomized clinical study of preoperative chemotherapy for esophageal carcinoma].", "Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer.", "Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone.", "Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagus: a prospective randomized trial.", "Randomized clinical trial of preoperative and postoperative adjuvant chemotherapy with cisplatin, vindesine, and bleomycin for carcinoma of the esophagus." ]

[ "A prospective study was performed to clarify the surgical outcome of patients with esophageal carcinoma who would benefit from induction chemotherapy followed by surgery. Of 55 eligible patients, 42 (76.3%) agreed to randomization with either chemotherapy followed by surgery (n = 21) or surgery alone (n = 21). The other 13 refused. The chemotherapy consisted of cisplatin, 5-fluorouracil and leucovorin. All 55 patients underwent esophagectomy with two- or three-field resection, including two (3.6%) hospital mortalities. Of the 21 patients receiving chemotherapy, the response rate was 33.3% after the first course and 60% after the second course. A complete response was not obtained. Responders to the first course showed a prolonged survival, however time to treatment failure did not differ between patients treated with chemotherapy followed by surgery or surgery alone. This chemotherapy offered a worse surgical outcome for patients with pretreatment diagnosis of T3. Multivariate analysis identified a partial response to the first course of chemotherapy to be a favorable prognostic indicator. Preoperative chemotherapy does not give a survival benefit over surgery alone for patients with advanced tumor (T3). Initial response to the first dose of chemotherapy is deemed to be a prognostic factor for patients with less advanced tumor (T1/T2).", "Of 77 patients with potentially resectable squamous cell carcinoma of the esophagus who were asked to participate in a phase III trial of treatment with either immediate surgery (n = 24) or surgery plus preoperative chemotherapy (n = 22), only 46 agreed to randomization. A priori, 13 patients chose chemotherapy before surgery and 18 patients chose surgery only. The complete chemotherapy program consisted of three cycles with fluorouracil, 1 g/m2 per day for 5 days, and cisplatin, 20 mg/m2 per day for 5 days. The response rate to chemotherapy was 50% (17 of 34 patients). Side effects of therapy were higher than expected based on results of previous phase II studies. Two drug-related deaths were observed. The resectability rate for patients in the surgery only group was 79% (33 of 42 patients) compared with 70% (19 of 27 patients) for patients receiving chemotherapy. The postoperative rates of septic complications (41% [11 of 27 patients] vs 26% [11 of 42 patients]) and respiratory disorders (48% [13 of 27 patients] vs 31% [13 of 42 patients]) were higher for patients with preoperative chemotherapy than for those treated with surgery only. Surgery-related mortality was increased in the chemotherapy group (19% [five of 27 patients]) compared with the surgery only group (10% [four of 42 patients]). Patients responding to preoperative chemotherapy had prolonged survival (median, 13 months) compared with nonresponders (median, 5 months), but the median survival for the chemotherapy group and the surgery only group was identical (10 months). We conclude that the preoperative chemotherapy regime used in this multi-institutional trial neither influences resectability nor increases the overall survival of patients with localized esophageal cancer. However, preoperative chemotherapy is associated with considerable side effects and a high postoperative mortality rate.", "In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival.", "A prospective randomized phase III trial was carried out at Songklanagarind Hospital from August 1988 to December 1990. The objectives of the study were to evaluate the effect of chemotherapy regimen in squamous cell carcinoma of the esophagus and to determine whether induction chemotherapy improves symptom-free period and survival in these patients compared to surgical treatment alone. Twenty-four patients were randomized to receive 2 cycles of chemotherapy, cis-platinum 100 mg/m2 intravenously on day 1, bleomycin 10 mg/m2 loading dose on day 3, followed by 10 mg/m2/day continuous intravenous infusion on days 4 through 7, and vinblastine 3 mg/m2 given intravenously on days 1, 8, 15, 22. The cycle was repeated on day 29. Fifteen patients completed 2 courses of chemotherapy and among these, 2 patients had a complete clinical response (13%), 6 (40%) had a partial response, and 7 patients (47%) had no response. Four patients died during chemotherapy treatment. Grade 3 hematologic toxicity (ECOG criteria) was observed in 47% (7/15) of patients. Twenty-two patients were randomized to conventional treatment (surgery alone). Median survival time was 17 months in both groups. However, early survival appeared to be better in the control group. Kaplan-Meier survivals at 6 months were 69% and 89% and at 3 years were 31% and 36% for the induction chemotherapy group and control group, respectively. The survival time differences were not statistically significant (P = 0.186). These findings demonstrate that although this chemotherapy regimen had some effect on squamous cell carcinoma of esophagus, it did not improve survival. On the contrary, survival seems to be better in the control group. The 6-month survival discrepancy between both groups might be due to the poor nutritional status of our patients, who may better tolerate smaller dosages of chemotherapy.", "To evaluate the effect of preoperative chemotherapy on the prognosis of stage II or III patients with esophageal carcinoma.\n From February 1991 to June 1994, 50 patients with stage II, III esophageal carcinoma were treated with preoperative combination (CDDP) chemotherapy and compared with 50 patients received operation alone.\n The 5-year survival rate of the operation group and preoperative chemotherapy group was 32% and 46%, respectively. The difference was statistically significant.\n Preoperative chemotherapy improves survival of surgically treated esophageal cancer patients.", "We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer.\n Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival.\n Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites.\n Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.", "Surgery is the standard treatment for patients with resectable esophageal carcinoma, but the long term prognosis of these patients is unsatisfactory. Some randomized trials of preoperative chemotherapy suggest that the prognosis of patients who respond may be improved.\n This randomized, controlled trial compared patients with clinically resectable esophageal epidermoid carcinoma who underwent surgery alone (Arm A) with those who received preoperative chemotherapy (Arm B). Overall survival and the prognostic impact of major response to chemotherapy were analyzed. Forty-eight patients were enrolled in each arm. Chemotherapy consisted of two or three cycles of cisplatin (100 mg/m2 on Day 1) and 5- fluorouracil (1000 mg/m2 per day continuous infusion on Days 1-5). In both study arms, transthoracic esophagectomy plus two-field lymphadenectomy was performed. The two groups were comparable in terms of patient characteristics.\n Forty-seven patients were evaluable in each arm. The curative resection rate was 74.4% (35 of 47 patients) in Arm A and 78.7% (37 of 47 patients) in Arm B. Treatment-related mortality was 4.2% in both arms. The response rate to preoperative chemotherapy was 40% (19 of 47 patients), including 6 patients (12.8%) who achieved a pathologic complete responses. Overall survival was not improved significantly. The 19 patients in Arm B who responded to chemotherapy and underwent curative resection had significantly better 3-year and 5-year survival rates (74% and 60%, respectively) compared with both nonresponders (24% and 12%, respectively; P = 0.0002) and patients in Arm A who underwent complete resection (46% and 26%, respectively; P = 0.01): Patients who achieved a pathologic complete response (P = 0.01), but not those who achieved a partial response (P = 0.2), had significantly improved survival.\n Patients with resectable esophageal carcinoma who underwent preoperative chemotherapy and obtained a pathologic complete response had a significantly improved long term survival. Major efforts should be undertaken to identify patients before neoadjuvant treatments who are likely to respond.\n Copyright 2001 American Cancer Society.", "This study investigated the role of preoperative chemotherapy in squamous cell cancer of the esophagus.\n A prospective randomized trial was undertaken in 147 patients: 74 received preoperative chemotherapy comprising cisplatin and 5-fluorouracil and 73 had surgical therapy alone. End points were cancer and therapy-related deaths.\n Sixty-six patients (89%) in the chemotherapy group underwent resection compared with 69 (95%) in the control group (p = not significant). Of the 60 patients who had resection after completing the chemotherapy program, 35 (58%) had a significant response, of whom four (6.7%) had a complete pathologic response. Postoperative mortality rates were 8.3% and 8.7% in the chemotherapy and control groups, respectively (p = not significant). Significant downstaging was evident with chemotherapy; curative resections were possible in 67% of these patients compared with 35% in the control group (p = 0.0003). T3 and T4 tumors were found in 67% and 91% of the chemotherapy and control groups, respectively (p = 0.0002). The respective figures for N1 disease were 70% and 88% (p = 0.009). An intent-to-treat analysis of survival showed no significant difference between the two groups. Median survivals were 16.8 and 13 months, respectively (p = 0.17). Of those who completed the chemotherapy and resection, responders fared better than control patients. Median survivals were 42.2 months and 13.8 months, respectively (p = 0.003). Median survival (8.3 months) was worse for nonresponders than for control patients (p = 0.03). The recurrence pattern suggested a significant reduction in locoregional disease with chemotherapy.\n Preoperative chemotherapy was safe and resulted in significant downstaging and an increased likelihood of curative resection. Survival was not better than that in the surgery-alone group, but responders did fare better than nonresponders.", "Thirty-nine patients with potentially resectable cancer of the middle or lower esophagus who had not previously been treated were randomly assigned to receive either immediate operation (n = 20) or operation plus preoperative and postoperative therapy with cisplatin, vindesine, and bleomycin (n = 19). Patients were stratified by tumor size and location and by sex, with no significant differences appearing between the two treatment groups. Median follow-up for both groups was 30 months. The preoperative response rate to chemotherapy was 47%. The postoperative complication rate for patients in the operation-only group was 47%; it was 29% for patients receiving chemotherapy. The overall resectability rates were similar for the two groups. Patients responding to chemotherapy preoperatively had significantly prolonged survival (median greater than 20 months) when compared with either nonresponders (median 6.2 months) or patients receiving only operation (median 8.6 months). A highly significant correlation was noted between a weight loss of less than 10% and response to chemotherapy, which suggested that responses occurred in patients with less advanced disease. We conclude that preoperative and postoperative cisplatin, vindesine, and bleomycin chemotherapy has acceptable toxicity and does not increase the incidence of postoperative complications. The natural history of epidermoid carcinoma of the esophagus is altered and overall survival is prolonged for patients responding to preoperative chemotherapy. Potential responding patients can be identified by the degree of preoperative weight loss." ]

[ "7908800", "11270908", "8101126" ]

[ "Effects of concurrent diazepam treatment on the outcome of exposure therapy in agoraphobia.", "Absence of neuropsychologic deficits in patients receiving long-term treatment with alprazolam-XR for panic disorder.", "Alprazolam and exposure alone and combined in panic disorder with agoraphobia. A controlled study in London and Toronto." ]

[ "In a study designed to evaluate the impact of benzodiazepine use on the outcome of behaviour therapy, 91, severe, chronic agoraphobics (46 BDZ users and 45 non-users) were randomly allocated on a double-blind basis to in vivo exposure with low-dose diazepam (ED) or placebo (EP). Drug doses were adjusted on the basis of weekly psychiatric assessments over weeks 1-4. Patients had 8 x 2 hr exposure sessions (weeks 5-12) and were then withdrawn from medication (weeks 13-16). Re-assessments were completed at weeks 4, 12 and 16, and follow-up assessments at approx 20, 46 and 72 weeks. In the analysis of the results, the clinical outcome was evaluated in relation to the therapeutic regime (ED vs EP) and prior BDZ use (users vs non-users). The results showed that the ED group had greater changes in anxiety than the EP group during the drug manipulation phases (anxiety increasing during BDZ withdrawal). There were no group differences in agoraphobic symptoms and no evidence that the outcome of the behavior therapy was significantly affected by concurrent BDZ treatment. There were significant improvements in agoraphobic symptoms over the treatment period, with no evidence for relapse of treatment gains on withdrawal from BDZ, nor for differential responses over the one year follow-up. Initial differences between users and non-users were less marked than expected, although there was a trend for more drop-outs among users across both ED and EP groups.", "Studies to date on the effects of benzodiazepines on neuropsychologic function have yielded conflicting data with respect to the type, severity, and duration of deficits that may be induced by these agents. As part of a placebo-controlled trial of alprazolam-XR (extended release) administered in combination with cognitive-behavioral therapy in patients with panic disorder, a battery of tests was used to measure neuropsychologic function. Thirty-eight outpatients were randomly assigned to receive either alprazolam-XR or placebo. Dosages were titrated up so that the alprazolam group (N = 18) received a mean dose of 4 mg/day (reduced in two patients because of sedative side effects). Neuropsychologic function after 6 weeks of therapy at the target dosage was compared with baseline assessments in each group. Both groups showed a statistically significant improvement from baseline to repeated assessments on measures of attention, executive functioning, psychomotor speed, and visual memory (p < 0.001); these gains were attributed to a practice effect. No significant changes were noted in measures of learning, verbal memory, or reaction time, and neither group showed any deterioration from baseline to retesting in any aspect of neuropsychologic function. These findings call into question the assumption that long-term benzodiazepine therapy produces significant neuropsychologic deficit in patients with diagnosed anxiety disorders.", "A cross-national randomised trial of alprazolam for chronic panic disorder with agoraphobia was run. Compared with previous trials it had three new features: an exposure therapy contrast group, a six-month treatment-free follow-up, and a low rate of early placebo drop-outs ('non-evaluables'). The dose of alprazolam was high (5 mg/day). The 154 patients had eight weeks of: alprazolam and exposure (combined treatment); or alprazolam and relaxation (a psychological placebo); or placebo and exposure; or placebo and relaxation (double placebo). Drug taper was from weeks 8 to 16. Follow-up was to week 43. Results were similar at both sites. Treatment integrity was good. All four treatment groups, including double placebo, improved well on panic throughout. On non-panic measures, by the end of treatment, both alprazolam and exposure were effective, but exposure had twice the effect size of alprazolam. During taper and follow-up, gains after alprazolam were lost, while gains after exposure were maintained. Combining alprazolam with exposure marginally enhanced gains during treatment, but impaired improvement thereafter. The new features put previous trails in a fresh light. By the end of treatment, though gains on alprazolam were largely as in previous studies, on phobias and disability they were half those with exposure. Relapse was usual after alprazolam was stopped, whereas gains persisted to six-month follow-up after exposure ceased. Panic improved as much with placebo as with alprazolam or exposure." ]

[ "11833753", "10575661", "12729523", "10620007", "10634923", "15165613", "10850936", "19499738", "16014759", "16219988", "21418447", "17187606" ]

[ "Comparison of standard and immune-enhancing oral formulas in asymptomatic HIV-infected persons: a multicenter randomized controlled clinical trial.", "Glutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial.", "[Isolated dietary counselling program versus supplement and dietary counselling in patients with human immunodeficiency virus infection].", "Nutritional supplements combined with dietary counselling diminish whole body protein catabolism in HIV-infected patients.", "Oral supplements as adjunctive treatment to nutritional counseling in malnourished HIV-infected patients: randomized controlled trial.", "L-ornithine alpha-ketoglutarate in HIV infection: effects on muscle, gastrointestinal, and immune functions.", "Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study.", "[Use of spirulina supplement for nutritional management of HIV-infected patients: study in Bangui, Central African Republic].", "Features of whey protein concentrate supplementation in children with rapidly progressive HIV infection.", "Nutrition rehabilitation of HIV-infected and HIV-negative undernourished children utilizing spirulina.", "Pilot randomized trial of nutritional supplementation in patients with tuberculosis and HIV-tuberculosis coinfection receiving directly observed short-course chemotherapy for tuberculosis.", "The effect of nutritional support on weight gain of HIV-infected children with prolonged diarrhoea." ]

[ "Both standard and immune-enhancing oral formulas are widely used to forestall HIV wasting and to promote immune function. However, there is little scientific evidence to support the differential effects of these formulas in asymptomatic HIV disease. The aim of this study was to compare the effects of an immune-enhancing oral formula and a standard oral formula on nutrition and immune measures in asymptomatic HIV-infected persons. A secondary aim was to evaluate the feasibility of maintaining a diverse sample of outpatients on a long-term oral formula protocol.\n In this multicenter controlled nonblinded study, 90 asymptomatic HIV-infected persons with CD4 cell counts between 275 and 550 cells/mm3 were randomized to a control group; a standard oral formula group (Ensure Plus); or an immune-enhancing oral formula group (Advera). All groups received basic nutrition counseling. Participants were evaluated on nutrition, immune, and feasibility measures at 3-month intervals during the 12-month study period. Differences in nutrition and immune measures among the 3 groups were analyzed using the Kruskal-Wallis and Wilcoxon tests. Wilcoxon tests and correlation coefficients were used to analyze feasibility data.\n Sixty-six outpatients completed the 12-month study protocol. Among the 3 groups, there were no significant differences with respect to body weight, bioelectrical impedance analysis (BIA)-derived body cell and fat mass, daily caloric intake, and serum albumin at any of the study visits. Moreover, absolute CD4+ T lymphocytes and percentages did not significantly differ at any time point among the 3 groups. Acceptability and tolerance of the formulas were high for both the standard and immune-enhancing oral formula groups.\n Within the context and limitations of this study, standard and immune-enhancing oral formulas consumed daily for 1 year had no differential effects on nutrition or immune parameters in asymptomatic HIV-infected persons.", "Loss of body cell mass, the active functioning tissue of the body, commonly occurs in patients with human immunodeficiency virus (HIV) infection, and the extent of wasting is related to the length of survival. We evaluated the anabolic role of the amino acid L-glutamine (GLN) and antioxidants in a double-blind, placebo-controlled trial in 26 patients with > 5% weight loss since disease onset. Subjects received GLN-antioxidants (40 g/d) in divided doses or glycine (40 g/d) as the placebo for 12 wk. Throughout the study, the subjects were seen weekly by a nutritionist, and body weight, bioelectric impedance assessment, and nutritional counseling were performed. Twenty-one subjects completed the study, and the groups were well matched. The 5 patients excluded from analysis all met a priori exclusion criteria. Over 3 mo, the GLN-antioxidant group gained 2.2 kg in body weight (3.2%), whereas the control group gained 0.3 kg (0.4%, P = 0.04 for difference between groups). The GLN-antioxidant group gained 1.8 kg in body cell mass, whereas the control group gained 0.4 kg (P = 0.007). Intracellular water increased in the GLN-antioxidant group but not in the control group. In conclusion, GLN-antioxidant nutrient supplementation can increase body weight, body cell mass, and intracellular water when compared with placebo supplementation. GLN-antioxidant supplementation provides a highly cost-effective therapy for the rehabilitation of HIV+ patients with weight loss.", "Nutritional intervention is a controversial area. The aim of the study was to compare the influence on nutritional status of nutritional supplementation with a standard polymeric formula as well as nutritional counselling versus isolated nutritional counselling in a group of HIV-infected patients.\n There were 70 patients, 66 of whom were fully evaluated for each study end point after application of prospectively determined evaluability criteria. Of these, 35 were randomized to group I (standard formula) and 35 were randomized to unsupplemented group II. Group I patients received standard enteral formula (3 cans/day, 250 ml per can). Patients were submitted to a prospective serial assessment of their nutrition status (anthropometric and biochemical status) and the nutritional intake was determined by means of 24-hours written food records. Determinations were performed at baseline and at 3 months.\n Treatment with oral supplements in group I resulted in a significant and sustained increase in weight (2.75%; p < 0.05) which was mostly due to fat mass (10.8%; p < 0.05). In contrast, no changes were detected in group II patients. The increase in body weight and tricipital skinfold was significant in group I. Total body water and fat free-mass remained without changes. CD4 counts and viral load remained stable in both groups.\n Oral nutritional supplements for a 3-months period resulted in body weight gain in HIV-infected patients, increasing the fat mass. An isolated nutritional counselling did not result in such an increase.", "Weight loss and protein malnutrition are frequent complications in HIV-infected patients. The effect of an oral nutritional supplement combined with nutritional counselling on whole body protein metabolism was assessed.\n HIV-infected individuals with a body mass index < 21 kg m-2 or CD4-T cells < 500 micro L-1 in stable clinical condition were randomly allocated to [1] receive either oral nutritional supplements (containing 2510 kJ, complete macro- and micronutrients) and dietary counselling (n = 8), or [2] identical monitoring but no supplements or specific nutritional advice (controls, n = 7). Whole body leucine kinetics and leucine oxidation rate were determined by [1-13C]-leucine infusions and lean and fat mass were measured before and 12 weeks after intervention.\n Leucine oxidation (protein catabolism) decreased in the group receiving nutritional intervention from 0.33 +/- 0.02 to 0.26 +/- 0.02 micromol kg-1 min-1 after 12 weeks (P < 0.05; P < 0.05 vs. control group) but remained unchanged in the control group. Whole body leucine flux showed a tendency to decrease in the intervention group from 1.92 +/- 0.19 to 1.73 +/- 0.14 micromol kg-1 min-1 (P = 0.07) and remained unchanged in the control group (2.21 +/- 0.16 and 2.27 +/- 0.14 micromol kg-1 min-1, respectively). Lean body mass determined by bioelectrical impedance analysis increased in the nutritional intervention group from 84 +/- 2 to 86 +/- 2 per cent (P < 0.05) and fat mass decreased from 17 +/- 2 to 14 +/- 2 per cent (P < 0.05) of total body weight whereas neither mass changed in the control group. Nutritional intervention had no significant effect on lymphocyte CD4 counts, on plasma TNFR 55, TNFR 75 and ILR 2 concentrations and on quality of life.\n The data demonstrate an anticatabolic effect of nutritional supplements combined with dietary counselling in HIV-infected subjects. They suggest that diminished whole body protein catabolism resulted in a change of body composition (increased lean mass, decreased fat mass).", "To compare nutritional counseling with and without oral supplements in HIV-infected patients with recent weight loss.\n Randomized non-blinded controlled trial, stratified for change in antiretroviral treatment at baseline.\n HIV-infected patients with recent weight loss (> 5% of total, and >3% in the last month).\n Nutritional counseling to increase dietary intake by 600 kcal/day over 8 weeks; in group A (n=24) by normal food, and in group B (n=26) by a range of fortified drink supplements with a calorific value of 0.6 to 1.5 kcal/ml.\n Body composition by bioelectrical impedance analysis, dietary intake by 24 h recall.\n Fat free mass increased from baseline to week 8 (P<0.05) with no difference between groups A and B (P=0.97). Body cell mass and weight gain were not significant and equal between groups. Assessed at weeks 2 and 4, group B patients consumed 11 +/- 6 kcal/kg as supplements, and their total energy intake was 6 kcal/kg higher than in group A (P<0.01). Total energy intake was not different between groups at weeks 6 and 8.\n Nutritional counseling and oral supplements are both feasible methods to restore food energy intake in malnourished HIV-infected patients. Although normal food intake is partially replaced, oral supplements may improve the adherence to a weight gain regimen.\n Copyright 1999 Harcourt Publishers Ltd.", "There have been claims that l-ornithine alpha-ketoglutarate (OKG) exerts anticatabolic, anabolic, and immunomodulating properties. This study aimed at quantifying the effects of OKG on muscle force, body composition, and immune function in outpatients infected with the human immunodeficiency virus (HIV) and presenting weight loss.\n Forty-six HIV(+) patients were included in a double-blind, prospective, randomized, controlled trial for 12 wk (10 g/d of OKG or isonitrogenous placebo and nutritional counseling). Podometry, handgrip strength, step test, triceps skinfold thickness, 50-kHz bioelectrical impedance, 3-d diet record, CD4 cell count, HIV-1 RNA concentration (viral load), and gastrointestinal symptoms were assessed at 0, 4, 8, and 12 wk.\n At baseline, patients (OKG, n = 22; placebo, n = 24) has similar CD4 counts (338 +/- 172 and 310 +/- 136 cells/mL), viral load (3.6 +/- 1.3 and 3.5 +/- 1.3 log(10) copies/mL), body mass index (20.0 +/- 2.4 and 20.6 +/- 3.0 kg/m(2)), weight loss (9.0 +/- 3.12 and 9.4 +/- 3.0 kg), and food intake (2509 +/- 962 and 2610 +/- 808 kcal/d). Twenty-nine patients completed the protocol. Both groups increased their body mass index (P = 0.02 versus baseline) and triceps skinfold thickness (P < 0.01 versus baseline). They showed a similar positive correlation between handgrip strength and fat-free mass. Frequency of gastrointestinal symptoms increased in the OKG group (86% versus 54% in the placebo group, P = 0.025). No other differences were observed between groups.\n All patients increased their body mass index and triceps skinfold thickness due to food supplementation and diet counseling. Oral OKG failed to improve nutritional, functional, or immunologic status in these weight-losing HIV(+) patients and had important gastrointestinal side effects.", "The current study was designed to examine whether a combination of three nutrients, consisting of beta-hydroxy-beta-methylbutyrate (HMB), a metabolite of leucine, L-glutamine (Gln) and L-arginine (Arg), each of which has been previously shown to slow muscle proteolysis, could synergistically alter the course of muscle wasting in patients with established acquired immunodeficiency syndrome (AIDS).\n Sixty-eight human immunodeficiency virus (HIV)-infected patients with a documented weight loss of at least 5% in the previous 3 months were recruited from the HIV clinic at Nassau County Medical Center. The subjects were randomly assigned in a double-blind fashion to receive either placebo containing maltodextrin or the nutrient mixture (HMB/Arg/Gln) containing 3 g HMB, 14 g L-glutamine, and 14 g L-arginine given in two divided doses daily for 8 weeks. Body weights (BW) were recorded weekly and lean body mass (LBM) and fat mass (FM) were measured by air displacement plethysmography and by a single computerized tomography (CT) slice through the thigh at 0, 4, and 8 weeks.\n Forty-three subjects completed the 8-week protocol, (placebo, n = 21; HMB/Arg/Gln, n = 22). At 8 weeks, the subjects consuming the HMB/Arg/Gln mixture gained 3.0 +/- 0.5 kg of BW while those supplemented with the placebo gained 0.37 +/- 0.84 kg (p = .009). The BW gain in the HMB/Arg/Gln-treated subjects was predominantly LBM (2.55 +/- 0.75 kg) compared with the placebo-supplemented subjects who lost lean mass (-0.70 +/- 0.69 kg, p = .003). No significant change in FM gain was observed (0.43 +/- 0.83 kg for the group receiving HMB/Arg/Gln and 1.07 +/- 0.64 kg for the group receiving the placebo, p > .20). Similar percentage changes in muscle mass and fat mass were observed with CT scans. Immune status was also improved as evident by an increase in CD3 and CD8 cells and a decrease in the HIV viral load with HMB/Arg/Gln supplementation.\n The data indicate that the HMB/Arg/Gln mixture can markedly alter the course of lean tissue loss in patients with AIDS-associated wasting.", "Treatment of HIV-infected persons including nutritional management is a major concern in Africa and in particular in the Central African Republic (CAR). This six-month randomized prospective longitudinal study was carried out at the Friends of Africa Center that was a facility for comprehensive management of persons infected and affected by HIV in Banqui, CAR. The purpose of the study was to assess the impact of spirulina supplement on clinical and laboratory findings in HIV-infected patients who were not indications for ARV treatment. A total of 160 patients were randomly assigned to two groups. Patients in group 1 (n=79) received 10 grams of spirulina per day on a regular basis while patients in group 2 (n = 81) received a placebo. In addition patients in both groups received dietary products supplied by the World Food Program (WFP). Follow-up of the 160 patients at three and six months showed that 16 patients had been lost from follow-up and 16 had died, with no difference in distribution between the two groups. A significant improvement in the main follow-up criteria, i.e., weight, arm girth, number of infectious episodes, CD4 count, and protidemia, was observed in both groups. No difference was found between the two groups except with regard to protidemia and creatinemia that were higher in the group receiving spirulina supplement. From a clinical standpoint results were less clear-cut since the Karnofsky score was better in the group receiving spirulina than in the group receiving the placebo at 3 months but not at 6 months and fewer patients presented pneumonia at six months. Further study over a longer period will be needed to determine if spirulina is useful and to evaluate if higher doses can have beneficial nutritional and immunitary effects without adverse effects, in particular renal problems.", "HIV infection is associated with subnormal GSH levels. An increase in glutathione levels has been observed in HIV-infected adults under oral whey protein supplementation. We studied the features associated with a whey protein concentrate supplementation in children with rapidly progressive AIDS. A prospective double-blind clinical trial was carried out for 4 months with 18 vertically HIV-infected children (1.98-6.37 years), under antiretroviral therapy, who had received whey protein, maltodextrin (placebo) or none. Erythrocyte glutathione concentration, T lymphocyte counts (CD4+ and CD8+) and occurrence of associated co-infections were evaluated. Wilcoxon's and Fischer's Exact tests were used to assess differences between whey protein-supplemented and control (placebo and non-supplemented) groups. A significant median increase of 16.14 mg/dl (p = 0.018) in erythrocyte glutathione levels was observed in the whey protein-supplemented group; the TCD4/CD8 lymphocyte ratio showed a non significant increase and lower occurrence of associated co-infections was also observed. In conclusion, whey protein concentrate supplementation can stimulate glutathione synthesis and, possibly, decrease the occurrence of associated co-infections.", "The objective of this study was to assess the impact of an alimentary integrator composed of spirulina (Spirulina platensis; SP), produced at the Centre Médical St Camille of Ouagadougou, Burkina Faso, on the nutritional status of undernourished HIV-infected and HIV-negative children. We compared two groups of children: 84 were HIV-infected and 86 were HIV-negative. The duration of the study was 8 weeks. Anthropometric and haematological parameters allowed us to appreciate both the nutritional and biological effect of SP supplement to traditional meals. Rehabilitation with SP shows on average a weight gain of 15 and 25 g/day in HIV-infected and HIV-negative children, respectively. The level of anaemia decreased during the study in all children, but recuperation was less efficient among HIV-infected children. In fact 81.8% of HIV-negative undernourished children recuperated as opposed to 63.6% of HIV-infected children (Z: 1.70 (95% CI -0.366, -0.002, p = 0.088)). Our results confirm that SP is a good food supplement for undernourished children. In particular, rehabilitation with SP also seems to correct anaemia and weight loss in HIV-infected children, and even more quickly in HIV-negative undernourished children.", "To investigate the effects of nutritional supplementation on the outcome and nutritional status of south Indian patients with tuberculosis (TB) with and without human immunodeficiency virus (HIV) coinfection on anti-tuberculous therapy.\n Randomized controlled trial on the effect of a locally prepared cereal-lentil mixture providing 930 kcal and a multivitamin micronutrient supplement during anti-tuberculous therapy in 81 newly diagnosed TB alone and 22 TB-HIV-coinfected patients, among whom 51 received and 52 did not receive the supplement. The primary outcome evaluated at completion of TB therapy was outcome of TB treatment, as classified by the national programme. Secondary outcomes were body composition, compliance and condition on follow-up 1 year after cessation of TB therapy and supplementation.\n There was no significant difference in TB outcomes at the end of treatment, but HIV-TB coinfected individuals had four times greater odds of poor outcome than those with TB alone. Among patients with TB, 1/35 (2.9%) supplemented and 5/42(12%) of those not supplemented had poor outcomes, while among TB-HIV-coinfected individuals, 4/13 (31%) supplemented and 3/7 (42.8%) non-supplemented patients had poor outcomes at the end of treatment, and the differences were more marked after 1 year of follow-up. Although there was some trend of benefit for both TB alone and TB-HIV coinfection, the results were not statistically significant at the end of TB treatment, possibly because of limited sample size.\n Nutritional supplements in patients are a potentially feasible, low-cost intervention, which could impact patients with TB and TB-HIV. The public health importance of these diseases in resource-limited settings suggests the need for large, multi-centre randomized control trials on nutritional supplementation.\n © 2011 Blackwell Publishing Ltd.", "To examine the effect on growth and immunity of enhanced calorie and protein provision to HIV-infected children presenting with prolonged diarrhoea.\n A total of 169 HIV-infected children aged 6-36 months with diarrhoea for 7 days or more were randomly assigned to either standard nutrition support for children with prolonged diarrhoea or an enhanced diet started during hospitalisation and continued after discharge. The change in weight between enrolment and 8, 14 and 26 weeks and changes in plasma HIV-RNA and CD4 cell count at 8 and 26 weeks were estimated.\n Children receiving enhanced nutrition achieved significantly more weight gain (p < 0.001) between enrolment and 8 weeks than children on the standard diet (median increase in weight-for-age standard deviation score +1.02 vs. +0.01). After 8 weeks median weight velocity was normal and similar in both groups. The change in median CD4 count was similar in both groups. The 26-week mortality rate was high in both groups (standard support: 22%, enhanced support: 29%).\n Nutrition support of children with advanced HIV infection and prolonged diarrhoea resulted in significant and sustained weight gain, but did not improve CD4 counts or survival. These results support integrated nutrition interventions for HIV-infected children." ]

[ "9408812", "16730924", "16930863", "19058926", "15525998", "11593078", "8556974", "8745134", "8561098", "12873248", "16461866", "12233989", "18551884" ]

[ "Replacement medication for cocaine dependence: methylphenidate.", "Double-blind, placebo-controlled trial of selegiline transdermal system (STS) for the treatment of cocaine dependence.", "Treatment of cocaine dependent treatment seekers with adult ADHD: double-blind comparison of methylphenidate and placebo.", "Effects of oral methamphetamine on cocaine use: a randomized, double-blind, placebo-controlled trial.", "A double-blind, placebo-controlled trial of modafinil for cocaine dependence.", "Dextroamphetamine for cocaine-dependence treatment: a double-blind randomized clinical trial.", "Mazindol treatment for cocaine dependence.", "A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients.", "Mazindol for relapse prevention to cocaine abuse in methadone-maintained patients.", "Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence.", "Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained population.", "Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence.", "Bupropion hydrochloride versus placebo, in combination with cognitive behavioral therapy, for the treatment of cocaine abuse/dependence." ]

[ "Agonists, or \"replacement medications,\" are useful adjuncts in treatment of opiate and nicotine dependence. They have not been systematically examined in cocaine dependence. Results of early open trials with methylphenidate for treatment of cocaine dependence were equivocal. Twenty-four cocaine-dependent subjects were enrolled in an 11-week double-blind, placebo-controlled study of methylphenidate. Assignment was random. Intake included a 2-day human laboratory procedure in which subjects received initial doses of methylphenidate or placebo. Subjects attended the clinic Monday through Friday and received oral doses of methylphenidate (5 mg plus 20-mg sustained release) or placebo at 8:00 a.m., with afternoon and weekend take-home doses (20 mg sustained-release or placebo) provided in Medication Events Monitoring System bottles to monitor compliance. Clinic visits included therapy sessions, electrocardiograms, self-report measures, and twice-weekly urine screens. The two groups were equivalent in terms of retention (methylphenidate 48% and placebo 42%) and had similar cocaine use outcomes (40% benzoylecgonine-positive urine screens). There were no significant adverse effects. The doses were sufficient to permit detection of psychoactive effects (\"stimulant,\" \"more energy\") and side effects (\"jitteriness,\" \"eating less\") without increased \"craving.\" Additional medications with different effects profiles are being studied to further evaluate the replacement model in cocaine dependence.", "Cocaine dependence is a major public health problem for which there is no FDA-approved pharmacological treatment. Selegiline is an irreversible selective inhibitor of monoamine oxidase type B (MAO-B) which may affect cocaine addiction through several potential mechanisms. In this study, selegiline transdermal system (STS) was compared to placebo as a treatment for cocaine dependence. This multi-site, double-blind trial of 300 subjects with cocaine dependence assessed the efficacy of selegiline using subject self-reported cocaine use substantiated by urine benzoylecgonine (BE) as the primary outcome measure. Analysis of the data did not show a significant effect for selegiline over placebo. This study does not support a role for selegiline in treating cocaine dependence. The contrast of this result to earlier, promising preclinical and human pilot data could be due to factors associated with sample size, patient characteristics, dose, or poor predictive validity of preclinical models.", "The purpose of this double-blind 14-week trial was to compare the efficacy of sustained-release methylphenidate (MPH) to placebo (PBO) in treating adult attention deficit hyperactivity disorder (ADHD) symptoms in current cocaine dependent (CD) treatment seekers. The randomized sample consisted of 106 participants who were predominately male (83%) and 60% Caucasian, 14% Hispanic, 20% African-American and 6% other. All participants met DSM-IV criteria for ADHD and CD. There were no significant demographic differences between the two treatment groups. All participants received weekly individual cognitive behavioral therapy. There was no difference in retention rate based on treatment group (p=.91). The majority of the PBO group and the MPH group reported >30% improvement in their ADHD symptoms (55% versus 47%), with no significant difference between the two groups (p=.44). Using a combined outcome measure (>30% reduction in ADHD symptoms and CGI <3), the response rates were similar for both groups (28% PBO versus 30% MPH; p=.83). Longitudinal analyses of the urine toxicology data using generalized estimating equations, revealed a decrease in the probability of cocaine positive urine samples during the trial for the MPH group compared to the PBO group (p=.001). Further analysis suggested that for the MPH group, ADHD treatment responders, based on a semi structured clinical interview, were more likely to have a reduction in cocaine use compared to the non-ADHD responders. Although sustained-release MPH did not show superiority over PBO in treating ADHD symptoms, this trial provides some evidence that improvement in ADHD symptoms (clinician rated) among those patients receiving MPH, but not placebo, was associated with a reduction in cocaine use.", "No medication is currently approved for the treatment of cocaine dependence, but several preclinical and clinical reports suggest agonist-like medications, e.g., amphetamine analogues, may be a productive strategy for medication development.\n This current proof-of-concept study sought to evaluate the safety, tolerability, and effectiveness of methamphetamine as a candidate treatment for cocaine dependence.\n A randomized, double-blind, placebo-controlled study served to evaluate three treatment conditions in 82 cocaine-dependent individuals: (1) placebo (0mg, 6x/day; n=27), (2) immediate release (IR) methamphetamine (5mg, 6x/day; n=30), (3) sustained release (SR) methamphetamine (30 mg first pill, 1x/day; 0mg 5x/day; n=25). The study employed a sequential, two-phase design (i.e., 4 weeks of medication and counseling followed by 4 weeks of medication/counseling plus a contingency management procedure).\n Both preparation forms of methamphetamine were well-tolerated, with similar retention to placebo (0mg, 33%; 30 mg IR, 30%, 30 mg SR, 32%). Methamphetamine SR was associated with decreased sleep and increased weight loss. Medication adherence rates were high for the first dose of the day (95%), while adherence for subsequent capsules was lower. Those in the SR condition exhibited consistently lower rates of cocaine-positive urine samples (0mg, 60%; 30 mg IR, 66%; 30 mg SR, 29%), p<0.0001, and reported the greatest reduction in craving for cocaine, p<0.05.\n SR methamphetamine significantly reduced cocaine use and craving. Additional research is warranted to develop and evaluate agonist-like medications that may effectively treat cocaine dependence.", "Despite years of active research, there are still no approved medications for the treatment of cocaine dependence. Modafinil is a glutamate-enhancing agent that blunts cocaine euphoria under controlled conditions, and the current study assessed whether modafinil would improve clinical outcome in cocaine-dependent patients receiving standardized psychosocial treatment. This was a randomized, double-blind, placebo-controlled trial conducted at a university outpatient center (from 2002 to 2003) on a consecutive sample of 62 (predominantly African American) cocaine-dependent patients (aged 25-63) free of significant medical and psychiatric conditions. After screening, eligible patients were randomized to a single morning dose of modafinil (400 mg), or matching placebo tablets, for 8 weeks while receiving manual-guided, twice-weekly cognitive behavioral therapy. The primary efficacy measure was cocaine abstinence based on urine benzoylecgonine levels. Secondary measures were craving, cocaine withdrawal, retention, and adverse events. Modafinil-treated patients provided significantly more BE-negative urine samples (p=0.03) over the 8-week trial when compared to placebos, and were more likely to achieve a protracted period (> or =3 weeks) of cocaine abstinence (p=0.05). There were no serious adverse events, and none of the patients failed to complete the study as a result of adverse events. This study provides preliminary evidence, which should be confirmed by a larger study, that modafinil improves clinical outcome when combined with psychosocial treatment for cocaine dependence.", "A properly implemented agonist treatment regimen should improve retention and reduce illicit drug use. Cocaine-dependent subjects (N = 128) were enrolled in a 12-week randomized, double-blind, placebo-controlled trial. In the multistage dosing design, subjects initially received placebo (PBO) or 15 to 30 mg of dextroamphetamine sulfate, sustained-release capsules. At week 5, the dose doubled to 30 mg or 60 mg for active groups. Subjects attended the clinic twice a week, provided urine samples, obtained medication, and had one behavioral therapy session a week. Retention was best for the 15- to 30-mg group, whereas the proportion of benzoylecgonine-positive urine screens was, from lowest to highest, 30 to 60 mg, 15 to 30 mg, and PBO at study end. Dosing must be refined. The results provide support for additional examination of the agonist model in psychostimulant-dependence treatment.", "This double-blind placebo-controlled treatment study tested the efficacy of mazindol in currently cocaine-dependent out-patients. Forty-three patients were randomized to mazindol (2 mg QD) vs. placebo treatment for 6 weeks. All patients received weekly group counseling. Patients improved with respect to objective (urine toxicology) and subjective (self-report of times used, dollars spent, craving, etc.) measures. There was no response difference between patients treated with mazindol and those who received placebo.", "We conducted a multi-site, placebo-controlled, randomized double-blind clinical trial comparing bupropion HCL (300 mg/day) to placebo for the treatment of cocaine dependence in methadone-maintained subjects. A total of 149 subjects at three sites participated in a 12-week study. Outcome measures included cocaine use, level of depression, and psychosocial functioning. Results showed no significant differences between placebo and bupropion. Exploratory analyses suggested a medication effect for the subset of subjects depressed at study entry. The need to target subgroups of cocaine abusers in future pharmacotherapy trials and the possible role of treatment readiness are discussed.", "We conducted a double-blind, randomized clinical trial of mazindol (n = 37) for the prevention of relapse to cocaine abuse in methadone-maintained patients who were in the \"action\" stage of change, i.e., had a history of cocaine dependence but who had been abstinent for at least 2 weeks prior to entry into the study. Eight-one percent of subjects completed the 12-week course of treatment. Overall, cocaine use during the study was comparatively low-17% of the urine screens submitted were positive for cocaine metabolite. Differences between the mazindol and placebo groups of rates of relapse, number of days to relapse, and cocaine use did not reach statistical significance, but were in the direction of a treatment effect. Results suggest that stage of abstinence initiation may be a potentially useful category to employ as an independent variable in future pharmacotherapy trials for the treatment of cocaine addiction in this patient population.", "To establish the feasibility of conducting a placebo-controlled clinical trial of dexamphetamine replacement therapy for cocaine dependence and to obtain preliminary data.\n Double-blind randomized placebo-controlled trial.\n Thirty cocaine-dependent injecting drug users.\n Subjects were assigned randomly to receive 60 mg/day dexamphetamine (n = 16) or placebo (n = 14) for 14 weeks.\n Immunoassay and mass spectrometric techniques were used to identify cocaine metabolites in urine. Subjects were screened using the Composite International Diagnostic Interview and DSM-IV. The Opiate Treatment Index, Brief Symptom Inventory, Severity of Dependence Scale and visual analogue craving scales were used to collect pre- and post-self-report data.\n Treatment retention was equivalent between groups; however, outcomes favoured the treatment group with no improvements observed in the placebo control group. The proportion of cocaine-positive urine samples detected in the treatment group declined from 94% to 56% compared to no change in the placebo group (79% positive). While the improvements were not significant between groups, within-group analysis revealed that the treatment group reduced self-reported cocaine use (P = 0.02), reduced criminal activity (P = 0.04), reduced cravings (P < 0.01) and reduced severity of cocaine dependence (P < 0.01) with no within-group improvements found in the placebo group.\n A definitive evaluation of the utility of dexamphetamine in the management of cocaine dependence is feasible and warranted.", "No effective pharmacotherapies exist for cocaine dependence, although contingency management (CM) has demonstrated efficacy.\n To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals.\n This 25-week, placebo-controlled, double-blind trial randomly assigned participants to 1 of 4 treatment conditions: CM and placebo (CMP), CM and 300 mg/d of bupropion hydrochloride (CMB), voucher control and placebo (VCP), or voucher control and bupropion (VCB).\n Outpatient clinic at the Veterans Affairs Connecticut Healthcare System.\n A total of 106 opiate-dependent, cocaine-abusing individuals.\n All study participants received methadone hydrochloride (range, 60-120 mg). Participants receiving bupropion hydrochloride were given 300 mg/d beginning at week 3. In the CM conditions, each urine sample negative for both opioids and cocaine resulted in a monetary-based voucher that increased for consecutively drug-free urine samples during weeks 1 to 13. Completion of abstinence-related activities also resulted in a voucher. During weeks 14 to 25, only completion of activities was reinforced in the CM group, regardless of sample results. The voucher control groups received vouchers for submitting urine samples, regardless of results, throughout the study.\n Thrice-weekly urine toxicologic test results for cocaine and heroin.\n Groups did not differ in baseline characteristics or retention rates. Opiate use decreased significantly, with all treatment groups attaining equivalent amounts of opiate use at the end of the study. In the CMB group, the proportion of cocaine-positive samples significantly decreased during weeks 3 to 13 (P<.001) relative to week 3 and remained low during weeks 14 to 25. In the CMP group, cocaine use significantly increased during weeks 3 to 13 (P<.001) relative to week 3, but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 (P<.001). In contrast, by treatment end, the VCB and VCP groups showed no significant improvement in cocaine use.\n These findings suggest that combining CM with bupropion for the treatment of cocaine addiction may significantly improve outcomes relative to bupropion alone.", "In this 12-week double-blind placebo-controlled trial of methylphenidate (MTP) versus placebo in 48 cocaine-dependent attention-deficit/hyperactivity disorder (ADHD) adults, the authors sought to determine whether MTP would be safe, control ADHD symptoms, and affect cocaine use. Efficacy indexes revealed significantly greater ADHD symptom relief in the MTP group. There were no group differences in self-reported cocaine use, urinalysis results, or cocaine craving. Because of the relatively small sample size, the results are preliminary. However, we found that MTP improved subjective reports of ADHD symptoms and did not worsen cocaine use while participants were in treatment.", "Bupropion hydrochloride is a dopamine and norepinephrine reuptake inhibitor which may be an effective treatment for cocaine dependence due to its ability to reverse deficits in dopaminergic functioning that occur in chronic cocaine users. We performed a randomized, double-blind, placebo controlled trial comparing outpatient treatment with bupropion (N = 37) and placebo (N = 33) in combination with standard cognitive behavioral therapy. There were no statistically significant differences between bupropion and placebo in treatment outcomes, including aggregate measures of urine drug screen results (Joint Probability Index at 16 weeks: 0.43 for bupropion and 0.38 for placebo), treatment retention, cocaine craving ratings, and assessments of depressive symptoms. The failure to find an effect for bupropion relative to placebo, when combined with standard cognitive behavioral therapy, dampens enthusiasm for future development of bupropion as a cocaine pharmacotherapy." ]

[ "12351954", "12173139", "10465076", "15213046" ]

[ "Randomized trial of vitamin supplements in relation to transmission of HIV-1 through breastfeeding and early child mortality.", "Antenatal vitamin A supplementation increases birth weight and decreases anemia among infants born to human immunodeficiency virus-infected women in Malawi.", "Randomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child HIV-1 transmission in Durban, South Africa. South African Vitamin A Study Group.", "Effect of multimicronutrient supplementation on gestational length and birth size: a randomized, placebo-controlled, double-blind effectiveness trial in Zimbabwe." ]

[ "HIV-1 transmission through breastfeeding is a global problem and has been associated with poor maternal micronutrient status.\n A total of 1078 HIV-infected pregnant women from Tanzania were randomly assigned to vitamin A or multivitamins excluding A from approximately 20 weeks' gestation and throughout lactation.\n Multivitamins excluding A had no effect on the total risk of HIV-1 transmission (RR 1.04, 95% CI 0.82-1.32, P= 0.76). Vitamin A increased the risk of transmission (RR 1.38, 95% CI 1.09-1.76, P = 0.009). Multivitamins were associated with non-statistically significant reductions in transmission through breastfeeding, and mortality by 24 months among those alive and not infected at 6 weeks. Multivitamins significantly reduced breastfeeding transmission in infants of mothers with low baseline lymphocyte counts (RR 0.37; 95% CI 0.16-0.85, P = 0.02) compared with infants of mothers with higher counts (RR 0.99, 95% CI 0.68-1.45, P = 0.97; -for-interaction 0.03). Multivitamins also protected against transmission among mothers with a high erythrocyte sedimentation rate (P-for-interaction 0.06), low hemoglobin (P-for-interaction 0.06), and low birthweight babies (P-for-interaction 0.04). Multivitamins reduced death and prolonged HIV-free survival significantly among children born to women with low maternal immunological or nutritional status. Vitamin A alone increased breastfeeding transmission but had no effect on mortality by 24 months.\n Vitamin A increased the risk of HIV-1 transmission. Multivitamin (B, C, and E) supplementation of breastfeeding mothers reduced child mortality and HIV-1 transmission through breastfeeding among immunologically and nutritionally compromised women. The provision of these supplements to HIV-infected lactating women should be considered.", "Vitamin A is essential for immunity and growth. A controlled clinical that involved 697 human immunodeficiency virus (HIV)-infected pregnant women was conducted to determine whether vitamin A prevents anemia, low birth weight, growth failure, HIV transmission, and mortality. Women received daily doses of iron and folate, either alone or combined with vitamin A (3 mg retinol equivalent), from 18-28 weeks' gestation until delivery. In the vitamin A and control groups, respectively, the mean (+/-SE) birth weights were 2895+/-31 g and 2805+/-32 g (P=.05), the proportions of low-birth-weight infants were 14.0% and 21.1% (P=.03), the proportions of anemic infants at 6 weeks postpartum were 23.4% and 40.6% (P<.001), and the respective cumulative proportions of infants who were HIV infected at 6 weeks and 24 months of age were 26.6% and 27.8% (P=.76) and 27.7% and 32.8% (P=.21). Receipt of vitamin A improved birth weight and neonatal growth and reduced anemia, but it did not affect perinatal HIV transmission.", "Poor vitamin A status has been associated with a higher risk for mother-to-child transmission of HIV-1 and there is contradictory evidence on the impact of vitamin A on perinatal outcome. We therefore assessed the effect of vitamin A supplementation to mothers on birth outcome and mother-to-child transmission of HIV-1.\n In Durban, South Africa 728 pregnant HIV infected women received either vitamin A (368) or placebo (360) in a randomized, double-blind trial. The vitamin A treatment consisted of a daily dose of 5000 IU retinyl palmitate and 30 mg beta-carotene during the third trimester of pregnancy and 200000 IU retinyl palmitate at delivery. HIV infection results were available on 632 children who were included in the Kaplan-Meier transmission analysis. Results are reported on mother-to-child transmission rates up to 3 months of age.\n There was no difference in the risk of HIV infection by 3 months of age between the vitamin A [20.3%; 95% confidence interval (CI), 15.7-24.9] and placebo groups (22.3%; 95% CI, 17.5-27.1), nor were there differences in foetal or infant mortality rates between the two groups. Women receiving vitamin A supplement were, however, less likely to have a preterm delivery (11.4% in the vitamin A and 17.4% in the placebo group; P = 0.03) and among the 80 preterm deliveries, those assigned to the vitamin A group were less likely to be infected (17.9%; 95% CI, 3.5-32.2) than those assigned to the placebo group (33.8%; 95% CI, 19.8-47.8).\n Vitamin A supplementation, a low-cost intervention, does not appear to be effective in reducing overall mother-to-child transmission of HIV; however, its potential for reducing the incidence of preterm births, and the risk of mother-to-child transmission of HIV in these infants needs further investigation.", "Multiple micronutrient deficiencies may contribute to low birth weight, which is a major global determinant of mortality.\n We assessed the effect of prenatal multimicronutrient supplementation on gestational length and birth size.\n We conducted a randomized, placebo-controlled, double-blind effectiveness trial among antenatal care attendees in Harare, Zimbabwe. Pregnant women (22-35 wk of gestation) were randomly allocated to receive a multimicronutrient or placebo supplement daily until delivery. Supplementation with iron and folic acid was part of antenatal care.\n Of 1669 women, birth data were available from 1106 (66%), of whom 360 (33%) had HIV infection. The mean gestational length was 39.1 wk, and 16.6% of the women had a gestational length < 37 wk. The mean birth weight was 3030 g, and 10.5% of the infants had a birth weight < 2500 g. Multimicronutrient supplementation was associated with tendencies for increased gestational length (0.3 wk; 95% CI: -0.04, 0.6 wk; P = 0.06), birth weight (49 g; -6, 104 g; P = 0.08), and head circumference (0.2 cm; -0.02, 0.4 cm; P = 0.07) but was not associated with low birth weight (birth weight < 2500 g) (relative risk: 0.84; 0.59, 1.18; P = 0.31). The effect of multimicronutrient supplementation on birth weight was not significantly different between HIV-uninfected (26 g; -38, 91 g) and HIV-infected (101 g; -3, 205 g) subjects (interaction, P > 0.10).\n Antenatal multimicronutrient supplementation may be one strategy to increase birth size." ]

[ "12975221", "14988972", "10230742", "18172036", "15360790", "18373141", "8506888", "12716811", "11706929", "8591371", "16191138", "11575289", "11158489", "14687254", "12183309", "15762903", "12558230", "15802479", "15758007", "16880458", "17302768", "12610033", "8687263", "9292842", "14604272", "17911873", "16622171" ]

[ "The medical office of the 21st century (MOXXI): effectiveness of computerized decision-making support in reducing inappropriate prescribing in primary care.", "Opportunistic electronic reminders. Improving performance of preventive care in general practice.", "A randomized trial of a computer-based intervention to reduce utilization of redundant laboratory tests.", "Electronic alerts versus on-demand decision support to improve dyslipidemia treatment: a cluster randomized controlled trial.", "Effectiveness of an electronic medical record clinical quality alert prepared by off-line data analysis.", "Impact of computerized decision support on blood pressure management and control: a randomized controlled trial.", "Computerized medical records and preventive health care: success depends on many factors.", "Effects of an automated electronic reminder in changing the antiplatelet drug-prescribing behavior among Italian general practitioners in diabetic patients: an intervention trial.", "Lessons from a randomized controlled trial designed to evaluate computer decision support software to improve the management of asthma.", "A clinical trial of a knowledge-based medical record.", "Patients and computers as reminders to screen for diabetes in family practice. Randomized-controlled trial.", "A computerized reminder system to increase the use of preventive care for hospitalized patients.", "A randomized controlled trial of point-of-care evidence to improve the antibiotic prescribing practices for otitis media in children.", "Effects of computerized guidelines for managing heart disease in primary care.", "Cluster randomised controlled trial of tailored interventions to improve the management of urinary tract infections in women and sore throat.", "Can computer-generated evidence-based care suggestions enhance evidence-based management of asthma and chronic obstructive pulmonary disease? A randomized, controlled trial.", "Improvement of intraoperative antibiotic prophylaxis in prolonged cardiac surgery by automated alerts in the operating room.", "A randomized trial of electronic clinical reminders to improve quality of care for diabetes and coronary artery disease.", "Electronic alerts to prevent venous thromboembolism among hospitalized patients.", "Improving blood pressure control through provider education, provider alerts, and patient education: a cluster randomized trial.", "Assessment of education and computerized decision support interventions for improving transfusion practice.", "A controlled trial of web-based diabetes disease management: the MGH diabetes primary care improvement project.", "Computer reminders to implement preventive care guidelines for hospitalized patients.", "A randomized trial of \"corollary orders\" to prevent errors of omission.", "The impact of computerized clinical reminders on physician prescribing behavior: evidence from community oncology practice.", "Physicians' response to guided geriatric dosing: initial results from a randomized trial.", "Prescribers' responses to alerts during medication ordering in the long term care setting." ]

[ "Adverse drug-related events are common in the elderly, and inappropriate prescribing is a preventable risk factor. Our objective was to determine whether inappropriate prescribing could be reduced when primary care physicians had computer-based access to information on all prescriptions dispensed and automated alerts for potential prescribing problems.\n We randomly assigned 107 primary care physicians with at least 100 patients aged 66 years and older (total 12 560) to a group receiving computerized decision-making support (CDS) or a control group. Physicians in the CDS group had access to information on current and past prescriptions through a dedicated computer link to the provincial seniors' drug-insurance program. When any of 159 clinically relevant prescribing problems were identified by the CDS software, the physician received an alert that identified the nature of the problem, possible consequences and alternative therapy. The rate of initiation and discontinuation of potentially inappropriate prescriptions was assessed over a 13-month period.\n In the 2 months before the study, 31.8% of the patients in the CDS group and 33.3% of those in the control group had at least 1 potentially inappropriate prescription. During the study the number of new potentially inappropriate prescriptions per 1000 visits was significantly lower (18%) in the CDS group than in the control group (relative rate [RR] 0.82, 95% confidence interval [CI] 0.69-0.98), but differences between the groups in the rate of discontinuation of potentially inappropriate prescriptions were significant only for therapeutic duplication by the study physician and another physician (RR 1.66, 95% CI 0.99-2.79) and drug interactions caused by prescriptions written by the study physician (RR 2.15, 95% CI 0.98-4.70).\n Computer-based access to complete drug profiles and alerts about potential prescribing problems reduces the rate of initiation of potentially inappropriate prescriptions but has a more selective effect on the discontinuation of such prescriptions.", "Preventive care is an important role for general practitioners, yet opportunities for prevention are often missed.\n We provided an automatic electronic record preventive care reminder system for 12 preventive care activities for one 10 doctor practice. All patients who attended were randomised by the terminal digit of their record number.\n The control uptake of opportunistic prevention was low; ranging from 1.5% (tetanus immunisation) to 27% (influenza immunisation). The reminders increased this by significant but small amounts for four out of 12 activities (immunisation for tetanus and pneumococcus and recording of allergies and weight), insignificant increases for four (mumps, measles and rubella immunisation, recording of smoking, and taking of cervical smears and of blood pressure), and insignificantly decreased influenza immunisation, and screening for diabetes and hyperlipidaemia.\n Opportunistic electronic reminders have the potential to increase preventive care in general practice.", "To determine the impact of giving physicians computerized reminders about apparently redundant clinical laboratory tests.\n We performed a prospective randomized controlled trial that included all inpatients at a large teaching hospital during a 15-week period. The intervention consisted of computerized reminders at the time a test was ordered that appeared to be redundant. Main outcome measures were the proportions of clinical laboratory orders that were canceled and the proportion of the tests that were actually performed.\n During the study period, there were 939 apparently redundant laboratory tests among the 77,609 study tests that were ordered among the intervention (n = 5,700 patients) and control (n = 5,886 patients) groups. In the intervention group, 69% (300 of 437) of tests were canceled in response to reminders. Of 137 overrides, 41% appeared to be justified based on chart review. In the control group, 51% of ordered redundant tests were performed, whereas in the intervention group only 27% of ordered redundant tests were performed (P <0.001). However, the estimated annual savings in laboratory charges was only $35,000. This occurred because only 44% of redundant tests performed had computer orders, because only half the computer orders were screened for redundancy, and because almost one-third of the reminders were overridden.\n Reminders about orders for apparently redundant laboratory tests were effective when delivered. However, the overall effect was limited because many tests were performed without corresponding computer orders, and many orders were not screened for redundancy.", "Indirect evidence shows that alerting users with clinical decision support systems seems to change behavior more than requiring users to actively initiate the system. However, randomized trials comparing these methods in a clinical setting are lacking. We studied the effect of both alerting and on-demand decision support with respect to screening and treatment of dyslipidemia based on the guidelines of the Dutch College of General Practitioners.\n In a clustered randomized trial design, 38 Dutch general practices (77 physicians) and 87,886 of their patients (39,433 men 18 to 70 years of age and 48,453 women 18 to 75 years of age) who used the ELIAS electronic health record participated. Each practice was assigned to receive alerts, on-demand support, or no intervention. We measured the percentage of patients screened and treated after 12 months of follow-up. In the alerting group, 65% of the patients requiring screening were screened (relative risk versus control=1.76; 95% confidence interval, 1.41 to 2.20) compared with 35% of patients in the on-demand group (relative risk versus control=1.28; 95% confidence interval, 0.98 to 1.68) and 25% of patients in the control group. In the alerting group, 66% of patients requiring treatment were treated (relative risk versus control=1.40; 95% confidence interval, 1.15 to 1.70) compared with 40% of patients (relative risk versus control=1.19; 95% confidence interval, 0.94 to 1.50) in the on-demand group and 36% of patients in the control group.\n The alerting version of the clinical decision support systems significantly improved screening and treatment performance for dyslipidemia by general practitioners.", "We tested whether off-line data analysis, instead of event monitoring, was a viable method for initiating a clinical quality alert. A cohort of patients eligible for an alert was identified by off-line data analysis and a flag was set in their ambulatory Electronic Medical Records. One hundred clinicians were randomly assigned either to a control group or to a group that received the alert when viewing the electronic medical record of eligible patients. Primarily due to actions of their clinicians, 315 of the 580 patients (54.3%) seen by alerted clinicians were no longer eligible for the alert at the end of the one month study, compared to 128 of the 496 patients (25.8%) seen by control clinicians (p<.001). When not alerted, Allied Health clinicians were less likely than physicians to prescribe aspirin, but they responded similarly to the alert. There were no differences in response by specialty or gender of the clinician. Off-line data analysis proved to be an effective method of initiating a clinical alert.", "We conducted a cluster randomized controlled trial to examine the effectiveness of computerized decision support (CDS) designed to improve hypertension care and outcomes in a racially diverse sample of primary care patients.\n We randomized 2,027 adult patients receiving hypertension care in 14 primary care practices to either 18 months of their physicians receiving CDS for each hypertensive patient or to usual care without computerized support for the control group. We assessed prescribing of guideline-recommended drug therapy and levels of blood pressure control for patients in each group and examined if the effects of the intervention differed by patients' race/ethnicity using interaction terms.\n Rates of blood pressure control were 42% at baseline and 46% at the outcome visit with no significant differences between groups. After adjustment for patients' demographic and clinical characteristics, number of prior visits, and levels of baseline blood pressure control, there were no differences between intervention groups in the odds of outcome blood pressure control. The use of CDS to providers significantly improved Joint National Committee (JNC) guideline adherent medication prescribing compared to usual care (7% versus 5%, P < 0.001); the effects of the intervention remained after multivariable adjustment (odds ratio [OR] 1.39 [CI, 1.13-1.72]) and the effects of the intervention did not differ by patients' race and ethnicity.\n CDS improved appropriate medication prescribing with no improvement in disparities in care and overall blood pressure control. Future work focusing on improvement of these interventions and the study of other practical interventions to reduce disparities in hypertension-related outcomes is needed.", "To study the effect of a computerized medical record and other practice factors on the delivery of preventive health care.\n Prospective, controlled trial.\n University general internal medicine teaching clinic.\n Forty-five internal medicine residents and their 4 supervising attending physicians.\n The study group used a computerized ambulatory medical record system that included health care maintenance reminders. The control group used a conventional paper record with a health care maintenance flow sheet.\n The computer reminders significantly increased health care maintenance recommendations made to patients for proctosigmoidoscopy, tetanus vaccination, influenza vaccination, and pneumococcal vaccination, but not for fecal occult blood testing, mammography, Pap smears, or serum thyroxine screening in the elderly. First-year residents were nearly twice as successful as third-year residents in overall health care maintenance. Success scores varied markedly depending on which attending physician was supervising the residents. We found a strong interaction among group assignment, supervising attending, and level of training such that the reminders doubled success scores among first-year residents supervised by two of the attending physicians but had little effect on other subgroups. The time of year and the format of the reminder also had important effects for some of the maneuvers.\n Although computerized medical records markedly improved the performance of prevention maneuvers by committed physicians, many physicians using computer systems failed to make use of the resource. The reasons for this were complex. Future work in this area should carefully control for personal behaviors and focus upon administrative changes that more effectively implement these potentially powerful tools.", "To evaluate whether an electronic reminder integrated into a routine computer system increases the use of antiplatelet drugs for diabetic patients among Italian general practitioners (GPs).\n A randomized controlled trial was carried out among 300 GPs and their patients selected from the Health Search Database. Among these, 150 GPs (intervention group) received instructions to activate an electronic reminder plus a letter summarizing the beneficial effects of antiplatelet drugs in diabetic patients with at least one additional cardiovascular risk factor (\"high risk\"), whereas the other 150 GPs (control group) received only the letter. The electronic reminder, integrated into a standard software system for the management of the daily clinical practice, was displayed when every participating GP opened the medical record of diabetic patients aged > or =30 years. Only high-risk diabetic patients were included in the analysis. Patients were considered under antiplatelet treatment if they received two or more prescriptions at baseline and during the follow-up.\n We selected 15,343 high-risk diabetic patients, 7,313 belonging to GPs of the control group and 8,030 belonging to GPs of the intervention group. Overall, 1,672 patients (22.9%) of the control group and 1,886 (23.5%) patients of the intervention group received antiplatelet drugs at baseline (P = N.S.). At the end of the follow-up, the number of treated patients was significantly increased in the intervention group (odds ratio 1.99, 95% CI 1.79-2.22) versus the control group. The effect of the electronic reminder was more relevant among those patients with one or more cardiovascular risk factors but without previous cardiovascular diseases (CVDs), compared with those with CVDs.\n These findings provide evidence for the effect of an electronic reminder in affecting the prescriptive behavior of GPs.", "To investigate whether computer decision support software used in the management of patients with asthma improves clinical outcomes.\n Randomized controlled trial with practices each reporting on 30 patients with asthma over a 6 month period.\n 447 patients were randomly selected from practice asthma registers managed by 17 general practices from throughout the UK. Intervention practices used the software during consultations with these patients throughout the study while control practices did not.\n Practice consultations, acute exacerbations of asthma, hospital contacts, symptoms on assessment and medication use. A smaller proportion of patients within the intervention group initiated practice consultations for their asthma: 34 (22%) vs 111 (34%), odds ratio (OR) = 0.59, 95% confidence interval (CI) (0.37-0.95); and suffered acute asthma exacerbations: 12 (8%) vs 57 (17%), OR = 0.43, 95% CI = 0.21-0.85 six months after the introduction of the computer decision support software. There were no discernable differences in reported symptoms, maintenance prescribing or use of hospital services between the two groups.\n The use of computer decision support software that implements guidelines during patient consultations may improve clinical outcomes for patients with asthma.", "To meet the needs of primary care physicians caring for patients with HIV infection, we developed a knowledge-based medical record to allow the on-line patient record to play an active role in the care process. These programs integrate the on-line patient record, rule-based decision support, and full-text information retrieval into a clinical workstation for the practicing clinician. To determine whether use of a knowledge-based medical record was associated with more rapid and complete adherence to practice guidelines and improved quality of care, we performed a controlled clinical trial among physicians and nurse practitioners caring for 349 patients infected with the human immuno-deficiency virus (HIV); 191 patients were treated by 65 physicians and nurse practitioners assigned to the intervention group, and 158 patients were treated by 61 physicians and nurse practitioners assigned to the control group. During the 18-month study period, the computer generated 303 alerts in the intervention group and 388 in the control group. The median response time of clinicians to these alerts was 11 days in the intervention group and 52 days in the control group (PJJ0.0001, log-rank test). During the study, the computer generated 432 primary care reminders for the intervention group and 360 reminders for the control group. The median response time of clinicians to these alerts was 114 days in the intervention group and more than 500 days in the control group (PJJ0.0001, log-rank test). Of the 191 patients in the intervention group, 67 (35%) had one or more hospitalizations, compared with 70 (44%) of the 158 patients in the control group (PJ=J0.04, Wilcoxon test stratified for initial CD4 count). There was no difference in survival between the intervention and control groups (P = 0.18, log-rank test). We conclude that our clinical workstation significantly changed physicians' behavior in terms of their response to alerts regarding primary care interventions and that these interventions have led to fewer patients with HIV infection being admitted to the hospital.", "In New Zealand, more than 5% of people aged 50 years and older have undiagnosed diabetes; most of them attend family practitioners (FPs) at least once a year.\n To test the effectiveness of patients or computers as reminders to screen for diabetes in patients attending FPs.\n A randomized-controlled trial compared screening rates in 4 intervention arms: patient reminders, computer reminders, both reminders, and usual care. The trial lasted 2 months. The patient reminder was a diabetes risk self-assessment sheet filled in by patients and given to the FP during the consultation. The computer reminder was an icon that flashed only for patients considered eligible for screening.\n One hundred and seven FPs.\n The primary outcome was whether each eligible patient, who attended during the trial, was or was not tested for blood glucose. Analysis was by intention to treat and allowed for clustering by FP.\n Patient reminders (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.21, 2.43), computer reminders (OR 2.55, 1.68, 3.88), and both reminders (OR 1.69, 1.11, 2.59) were all effective compared with usual care. Computer reminders were more effective than patient reminders (OR 1.49, 1.07, 2.07). Patients were more likely to be screened if they visited the FP repeatedly, if patients were non-European, if they were \"regular\" patients of the practice, and if their FP had a higher screening rate prior to the study.\n Patient and computer reminders were effective methods to increase screening for diabetes. However, the effects were not additive.", "Although they are effective in outpatient settings, computerized reminders have not been proved to increase preventive care in inpatient settings.\n We conducted a randomized, controlled trial to determine the effects of computerized reminders on the rates at which four preventive therapies were ordered for inpatients. During an 18-month study period, a computerized system processed on-line information for all 6371 patients admitted to a general-medicine service (for a total of 10,065 hospitalizations), generating preventive care reminders as appropriate. Physicians who were in the intervention group viewed these reminders when they were using a computerized order-entry system for inpatients.\n The reminder system identified 3416 patients (53.6 percent) as eligible for preventive measures that had not been ordered by the admitting physician. For patients with at least one indication, computerized reminders resulted in higher adjusted ordering rates for pneumococcal vaccination (35.8 percent of the patients in the intervention group vs. 0.8 percent of those in the control group, P<0.001), influenza vaccination (51.4 percent vs. 1.0 percent, P< 0.001), prophylactic heparin (32.2 percent vs. 18.9 percent, P<0.001), and prophylactic aspirin at discharge (36.4 percent vs. 27.6 percent, P<0.001).\n A majority of hospitalized patients in this study were eligible for preventive measures, and computerized reminders significantly increased the rate of delivery of such therapies.", "Prescribing practices for otitis media are not consistent with current evidence-based recommendations.\n To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written.\n Randomized, controlled trial.\n Primary care pediatric clinic affiliated with university training program. Intervention. A point-of-care evidence-based message system presenting real time evidence to providers based on their prescribing practice for otitis media.\n Proportion of prescriptions for otitis media that were for <10 days and frequency with which antibiotics were prescribed.\n Intervention providers had a 34% greater reduction in the proportion of time they prescribed antibiotics for <10 days. Intervention providers were less likely to prescribe antibiotics than were control providers.\n A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition.", "Electronic information systems have been proposed as one means to reduce medical errors of commission (doing the wrong thing) and omission (not providing indicated care).\n To assess the effects of computer-based cardiac care suggestions.\n A randomized, controlled trial targeting primary care physicians and pharmacists.\n A total of 706 outpatients with heart failure and/or ischemic heart disease.\n Evidence-based cardiac care suggestions, approved by a panel of local cardiologists and general internists, were displayed to physicians and pharmacists as they cared for enrolled patients.\n Adherence with the care suggestions, generic and condition-specific quality of life, acute exacerbations of their cardiac disease, medication compliance, health care costs, satisfaction with care, and physicians' attitudes toward guidelines.\n Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions. The intervention had no effect on physicians' adherence to the care suggestions (23% for intervention patients vs 22% for controls). There were no intervention-control differences in quality of life, medication compliance, health care utilization, costs, or satisfaction with care. Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients.\n Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease. Future studies must weigh the benefits and costs of different (and perhaps more Draconian) methods of affecting clinician behavior.", "To assess the effectiveness of tailored interventions to implement guidelines for urinary tract infections in women and sore throat.\n Unblinded, cluster randomised pretest-post-test trial.\n 142 general practices in Norway.\n 72 practices received interventions to implement guidelines for urinary tract infection and 70 practices received interventions to implement guidelines for sore throat, serving as controls for each other. 59 practices in the urinary tract infection group and 61 practices in the sore throat group completed the study. Outcomes were measured in 16 939 consultations for sore throat and 9887 consultations for urinary tract infection.\n Interventions were developed to overcome identified barriers to implementing the guidelines. The main components of the tailored interventions were patient educational material, computer based decision support and reminders, an increase in the fee for telephone consultations, and interactive courses for general practitioners and practice assistants.\n Changes in rates of use of antibiotics, laboratory tests, and telephone consultations. Results: Patients in the sore throat group were 3% less likely to receive antibiotics after the intervention. Women with symptoms of urinary tract infection in the intervention group were 5.1% less likely to have a laboratory test ordered. No significant differences were found between the groups for the other outcomes. Large variation was found across the included practices in the rates of antibiotic prescription, use of laboratory tests and telephone consultations, and in the extent of change for all three outcome measures.\n Passively delivered, complex interventions targeted at identified barriers to change had little effect in changing practice.", "Translation of evidence-based guidelines into clinical practice has been inconsistent. We performed a randomized, controlled trial of guideline-based care suggestions delivered to physicians when writing orders on computer workstations.\n Inner-city academic general internal medicine practice.\n Randomized, controlled trial of 246 physicians (25 percent faculty general internists, 75 percent internal medicine residents) and 20 outpatient pharmacists. We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease. Care suggestions concerning drugs and monitoring were delivered to a random half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations. A 2 x 2 factorial randomization of practice sessions and pharmacists resulted in four groups of patients: physician intervention, pharmacist intervention, both interventions, and controls. DATA EXTRACTION/COLLECTION METHODS: Adherence to the guidelines and clinical activity was assessed using patients' electronic medical records. Health-related quality of life, medication adherence, and satisfaction with care were assessed using telephone questionnaires.\n During their year in the study, patients made an average of five scheduled primary care visits. There were no differences between groups in adherence to the care suggestions, generic or condition-specific quality of life, satisfaction with physicians or pharmacists, medication compliance, emergency department visits, or hospitalizations. Physicians receiving the intervention had significantly higher total health care costs. Physician attitudes toward guidelines were mixed.\n Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease.", "To assess the impact of an automated intraoperative alert to redose prophylactic antibiotics in prolonged cardiac operations.\n Randomized, controlled, evaluator-blinded trial.\n University-affiliated hospital.\n Patients undergoing cardiac surgery that lasted more than 4 hours after the preoperative administration of cefazolin, unless they were receiving therapeutic antibiotics at the time of surgery.\n Randomization to an audible and visual reminder on the operating room computer console at 225 minutes after the administration of preoperative antibiotics (reminder group, n = 137) or control (n = 136). After another 30 minutes, the circulating nurse was required to indicate whether a follow-up dose of antibiotics had been administered.\n Intraoperative redosing was significantly more frequent in the reminder group (93 of 137; 68%) than in the control group (55 of 136; 40%) (adjusted odds ratio, 3.31; 95% confidence interval, 1.97 to 5.56; P < .0001). The impact of the reminder was even greater when compared with the 6 months preceding the study period (129 of 480; 27%; P < .001), suggesting some spillover effect on the control group. Redosing was formally declined for 19 of the 44 patients in the reminder group without redosing. The rate of surgical-site infection in the reminder group (5 of 137; 4%) was similar to that in the control group (8 of 136; 6%; P = .42), but significantly lower than that in the pre-study period (48 of 480; 10%; P = .02).\n The use of an automatic reminder system in the operating room improved compliance with guidelines on perioperative antibiotic prophylaxis.", "The aim of this study was to evaluate the impact of an integrated patient-specific electronic clinical reminder system on diabetes and coronary artery disease (CAD) care and to assess physician attitudes toward this reminder system.\n We enrolled 194 primary care physicians caring for 4549 patients with diabetes and 2199 patients with CAD at 20 ambulatory clinics. Clinics were randomized so that physicians received either evidence-based electronic reminders within their patients' electronic medical record or usual care. There were five reminders for diabetes care and four reminders for CAD care.\n The primary outcome was receipt of recommended care for diabetes and CAD. We created a summary outcome to assess the odds of increased compliance with overall diabetes care (based on five measures) and overall CAD care (based on four measures). We surveyed physicians to assess attitudes toward the reminder system.\n Baseline adherence rates to all quality measures were low. While electronic reminders increased the odds of recommended diabetes care (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.01-1.67) and CAD (OR 1.25, 95% CI 1.01-1.55), the impact of individual reminders was variable. A total of three of nine reminders effectively increased rates of recommended care for diabetes or CAD. The majority of physicians (76%) thought that reminders improved quality of care.\n An integrated electronic reminder system resulted in variable improvement in care for diabetes and CAD. These improvements were often limited and quality gaps persist.", "Prophylaxis against deep-vein thrombosis in hospitalized patients remains underused. We hypothesized that the use of a computer-alert program to encourage prophylaxis might reduce the frequency of deep-vein thrombosis among high-risk hospitalized patients.\n We developed a computer program linked to the patient database to identify consecutive hospitalized patients at risk for deep-vein thrombosis in the absence of prophylaxis. The program used medical-record numbers to randomly assign 1255 eligible patients to an intervention group, in which the responsible physician was alerted to a patient's risk of deep-vein thrombosis, and 1251 patients to a control group, in which no alert was issued. The physician was required to acknowledge the alert and could then withhold or order prophylaxis, including graduated compression stockings, pneumatic compression boots, unfractionated heparin, low-molecular-weight heparin, or warfarin. The primary end point was clinically diagnosed, objectively confirmed deep-vein thrombosis or pulmonary embolism at 90 days.\n More patients in the intervention group than in the control group received mechanical prophylaxis (10.0 percent vs. 1.5 percent, P<0.001) or pharmacologic prophylaxis (23.6 percent vs. 13.0 percent, P<0.001). The primary end point occurred in 61 patients (4.9 percent) in the intervention group, as compared with 103 (8.2 percent) in the control group; the Kaplan-Meier estimates of the likelihood of freedom from deep-vein thrombosis or pulmonary embolism at 90 days were 94.1 percent (95 percent confidence interval, 92.5 to 95.4 percent) and 90.6 percent (95 percent confidence interval, 88.7 to 92.2 percent), respectively (P<0.001). The computer alert reduced the risk of deep-vein thrombosis or pulmonary embolism at 90 days by 41 percent (hazard ratio, 0.59; 95 percent confidence interval, 0.43 to 0.81; P=0.001).\n The institution of a computer-alert program increased physicians' use of prophylaxis and markedly reduced the rates of deep-vein thrombosis and pulmonary embolism among hospitalized patients at risk.\n Copyright 2005 Massachusetts Medical Society.", "Inadequate blood pressure control is a persistent gap in quality care.\n To evaluate provider and patient interventions to improve blood pressure control.\n Cluster randomized, controlled trial.\n 2 hospital-based and 8 community-based clinics in the Veterans Affairs Tennessee Valley Healthcare System.\n 1341 veterans with essential hypertension cared for by 182 providers. Eligible patients had 2 or more blood pressure measurements greater than 140/90 mm Hg in a 6-month period and were taking a single antihypertensive agent.\n Providers who cared for eligible patients were randomly assigned to receive an e-mail with a Web-based link to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) guidelines (provider education); provider education and a patient-specific hypertension computerized alert (provider education and alert); or provider education, hypertension alert, and patient education, in which patients were sent a letter advocating drug adherence, lifestyle modification, and conversations with providers (patient education).\n Proportion of patients with a systolic blood pressure less than 140 mm Hg at 6 months; intensification of antihypertensive medication.\n Mean baseline blood pressure was 157/83 mm Hg with no differences between groups (P = 0.105). Six-month follow-up data were available for 975 patients (73%). Patients of providers who were randomly assigned to the patient education group had better blood pressure control (138/75 mm Hg) than those in the provider education and alert or provider education alone groups (146/76 mm Hg and 145/78 mm Hg, respectively). More patients in the patient education group had a systolic blood pressure of 140 mm Hg or less compared with those in the provider education or provider education and alert groups (adjusted relative risk for the patient education group compared with the provider education alone group, 1.31 [95% CI, 1.06 to 1.62]; P = 0.012).\n Follow-up blood pressure measurements were missing for 27% of study patients. The study could not detect a mechanism by which patient education improved blood pressure control.\n A multifactorial intervention including patient education improved blood pressure control compared with provider education alone.", "Overuse of blood products is common, but prior efforts to improve transfusion decisions have met with limited success.\n This study examines transfusion practices before and after a conventional educational intervention followed by a randomized controlled trial of a decision support (DS) intervention with computerized physician order entry (CPOE) for red blood cell, platelet, and fresh-frozen plasma orders. The study was conducted in an academic medical center between April 2003 and June 2004. Orders originating from units not using CPOE with DS (e.g., the emergency department) were excluded. Junior housestaff were randomly assigned into a control group and an intervention group who received DS for transfusion orders. Transfusion orders were initially classified according to guideline rules as DS-agree or DS-disagree. Chart reviews assessed inappropriateness for all DS-disagree orders and a sample of DS-agree orders. The total of inappropriate transfusion orders included chart review confirmed DS-disagree orders and DS-agree orders reclassified as inappropriate.\n The percentages of inappropriate nonemergent transfusion orders during the baseline phase for the entire staff and randomly assigned junior housestaff were 72.6 percent (2154/2967) and 71.9 percent (1259/1752) and improved after conventional education to 63.8 percent (1699/2663; p < 0.0001) and 63.3 percent (1263/1996; p < 0.0001), respectively. The percentage of inappropriate orders in the DS intervention group continued to improve (59.6%, 804/1350; p < 0.0001). Physicians accepted 14 percent (133/939) of new DS-recommended orders, especially recommendations to increase transfusion doses (73%).\n Education and computerized DS both decreased the percentage of inappropriate transfusions, although the residual amount of inappropriate transfusions remained high.", "To test effects of a web-based decision support tool, the diabetes Disease Management Application (DMA), developed to improve evidence-based management of type 2 diabetes.\n We conducted a group randomized controlled trial of 12 intervention and 14 control staff providers and 307 intervention and 291 control patients with type 2 diabetes in a hospital-based internal medicine clinic. Providers were randomly assigned from May 1998 through April 1999 to have access to the DMA (intervention) or not to have access (control). The DMA displays interactive patient-specific clinical data, treatment advice, and links to other web-based care resources. We compared patients in the intervention and control groups for changes in processes and outcomes of care from the year preceding the study through the year of the study by intention-to-treat analysis.\n The DMA was used for 42% of scheduled patient visits. The number of HbA(1c) tests obtained per year increased significantly in the intervention group (+0.3 tests/year) compared with the control group (-0.04 tests/year, P = 0.008), as did the number of LDL cholesterol tests (intervention, +0.2 tests/year; control, +0.01 tests/year; P = 0.02) and the proportions of patients undergoing at least one foot examination per year (intervention, +9.8%; control, -0.7%; P = 0.003). Levels of HbA(1c) decreased by 0.2 in the intervention group and increased by 0.1 in the control group (P = 0.09); proportions of patients with LDL cholesterol levels <130 mg/dl increased by 20.3% in the intervention group and 10.5% in the control group (P = 0.5).\n Web-based patient-specific decision support has the potential to improve evidence-based parameters of diabetes care.", "Hospitalizations are an opportunity to provide preventive care.\n To determine if computer reminders, which we have shown to be effective in our ambulatory care setting, increasing the provision of inpatient preventive care.\n Randomized, controlled trial on the general medicine inpatient service of an urban, university-affiliated public hospital. Study subjects were 78 house staff rotating on the 6 general medicine services. The intervention was reminders to physicians printed on daily rounds reports about preventive care for which their patients were eligible, and suggested orders for preventive care provided through the physicians' workstations. The preventive care guidelines were derived from the US Preventive Care Task Force recommendations. Compliance with preventive care guidelines and house staff attitudes toward providing preventive care to hospitalized patients were the main outcome measures.\n No significant differences were seen between intervention and control physicians in compliance with preventive care guidelines in the aggregate or when individual preventive care actions individual preventive care actions were analyzed. This was true even though most physicians endorsed providing most kinds of preventive care for hospitalized patients.\n Despite past success in increasing preventive care in the outpatient setting, we were unable, using a moderately intensive intervention, to increase the provision of preventive care during hospitalizations. The physicians providing care during the hospitalization were not the patients' primary care physicians, which proved to be an important barrier. More intensive interventions, or more direct linkages between inpatient and outpatient care providers, may be required to overcome this resistance.", "Errors of omission are a common cause of systems failures. Physicians often fail to order tests or treatments needed to monitor/ameliorate the effects of other tests or treatments. The authors hypothesized that automated, guideline-based reminders to physicians, provided as they wrote orders, could reduce these omissions.\n The study was performed on the inpatient general medicine ward of a public teaching hospital. Faculty and housestaff from the Indiana University School of Medicine, who used computer workstations to write orders, were randomized to intervention and control groups. As intervention physicians wrote orders for 1 of 87 selected tests or treatments, the computer suggested corollary orders needed to detect or ameliorate adverse reactions to the trigger orders. The physicians could accept or reject these suggestions.\n During the 6-month trial, reminders about corollary orders were presented to 48 intervention physicians and withheld from 41 control physicians. Intervention physicians ordered the suggested corollary orders in 46.3% of instances when they received a reminder, compared with 21.9% compliance by control physicians (p < 0.0001). Physicians discriminated in their acceptance of suggested orders, readily accepting some while rejecting others. There were one third fewer interventions initiated by pharmacists with physicians in the intervention than control groups.\n This study demonstrates that physician workstations, linked to a comprehensive electronic medical record, can be an efficient means for decreasing errors of omissions and improving adherence to practice guidelines.", "The objective of this study is to examine the impact of a clinical reminder generated by an electronic medical record (EMR) system on physician prescribing behavior in community oncology practice setting. A case-control trial assessing the prescribing rates of erythropoietin by physicians is used. The participants and setting involves a total of 11,644 physician-patient encounters in 2 community oncology practices in the United States during a 21-month period. The intervention is a clinical reminder generated in real time during a physician-patient encounter by an EMR identifying cancer patients with low hemoglobin (Hgb) levels (ie, anemic), that is, patients with Hgb less then 12 g/dL. The main outcome measure is to determine the frequency of erythropoietin prescription by physicians to cancer patients with low Hgb levels. Implementation of a clinical reminder generated by way of an EMR significantly improved the likelihood of low-Hgb patients receiving treatment with erythropoietin. Low-Hgb patients in the experimental clinic during the time that the clinical reminder system was in place were almost twice as likely (ie, adjusted odds ratio = 1.92, P = .008) to have been treated with erythropoietin. The data support the effectiveness of clinical reminders as a way to influence physician prescribing behaviors and potentially improve the quality of patient care. However, we feel that there is a need to investigate the use of reminders in other aspects of cancer care that may be undertreated or when new drugs may be available but are underused.", "Guided dosing within a computerized provider order entry (CPOE) system is an effective method of individualizing therapy for patients. Physicians' responses to guided dosing decision support have not been extensively studied. As part of a randomized trial evaluating efficacy of dosing advice on reducing falls in the elderly, CPOE prompts to physicians for 88 drugs included tailored messages and guided dose lists with recommended initial doses and frequencies. The study captured all prescribing activity electronically. The primary outcome was the ratio between prescribed dose and recommended dose. Over 9 months, 778 providers entered 9111 study-related medication orders on 2981 patients. Physicians using guided orders chose recommended doses more often than controls(28.6% vs. 24.1%, p<0.001). Selected doses were significantly lower in the intervention group (median ratio of actual to recommended 2.5, interquartile range [1.0,4.0]) than the control group (median 3.0 interquartile range [1.5,5.0], p<0.001). While physicians selected the recommended dose less than a third of the time, guided geriatric dosing modestly improved compliance with guidelines.", "Computerized physician order entry with clinical decision support has been shown to improve medication safety in adult inpatients, but few data are available regarding its usefulness in the long-term care setting. The objective of this study was to examine opportunities for improving medication safety in that clinical setting by determining the proportion of medication orders that would generate a warning message to the prescriber via a computerized clinical decision support system and assessing the extent to which these alerts would affect prescribers' actions.\n The study was set within a randomized controlled trial of computerized clinical decision support conducted in the long-stay units of a large, academically-affiliated long-term care facility. In March 2002, a computer-based clinical decision support system (CDSS) was added to an existing computerized physician order entry (CPOE) system. Over a subsequent one-year study period, prescribers ordering drugs for residents on three resident-care units of the facility were presented with alerts; these alerts were not displayed to prescribers in the four control units.\n We assessed the frequency of drug orders associated with various categories of alerts across all participating units of the facility. To assess the impact of actually receiving an alert on prescriber behavior during drug ordering, we calculated separately for the intervention and control units the proportion of the alerts, within each category, that were followed by an appropriate action and estimated the relative risk of an appropriate action in the intervention units compared to the control units.\n During the 12 months of the study, there were 445 residents on the participating units of the facility, contributing 3,726 resident-months of observation time. During this period, 47,997 medication orders were entered through the CPOE system-approximately 9 medication orders per resident per month. 9,414 alerts were triggered (2.5 alerts per resident-month). The alert categories most often triggered were related to risks of central nervous system side-effects such as over-sedation (20%). Alerts for risk of drug-associated constipation (13%) or renal insufficiency/electrolyte imbalance (12%) were also common. Twelve percent of the alerts were related to orders for warfarin. Overall, prescribers who received alerts were only slightly more likely to take an appropriate action (relative risk 1.11, 95% confidence interval 1.00, 1.22). Alerts related to orders for warfarin or central nervous system side effects were most likely to engender an appropriate action, such as ordering a recommended laboratory test or canceling an ordered drug.\n Long-term care facilities must implement new system-level approaches with the potential to improve medication safety for their residents. The number of medication orders that triggered a warning message in this study suggests that CPOE with a clinical decision support system may represent one such tool. However, the relatively low rate of response to these alerts suggests that further refinements to such systems are required, and that their impact on medication errors and adverse drug events must be carefully assessed." ]

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[ "Systematic reviews reveal unrepresentative evidence for the development of drug formularies for poor and nonwhite populations.", "Reducing social inequalities in smoking: can evidence inform policy? A pilot study.", "The effectiveness of interventions to change six health behaviours: a review of reviews.", "Assessment of analysis by gender in the Cochrane reviews as related to treatment of cardiovascular disease.", "How many child deaths can we prevent this year?", "Improving services for disadvantaged childbearing women.", "Is health equity considered in systematic reviews of the Cochrane Musculoskeletal Group?", "Appraising the evidence: applying sex- and gender-based analysis (SGBA) to Cochrane systematic reviews on cardiovascular diseases.", "Tackling the wider social determinants of health and health inequalities: evidence from systematic reviews.", "Reducing stillbirths: interventions during labour.", "Evidence-based, cost-effective interventions: how many newborn babies can we save?", "Population tobacco control interventions and their effects on social inequalities in smoking: placing an equity lens on existing systematic reviews.", "Depression and anxiety.", "Reducing stillbirths: behavioural and nutritional interventions before and during pregnancy.", "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews.", "Effective/efficient mental health programs for school-age children: a synthesis of reviews.", "Supporting the delivery of cost-effective interventions in primary health-care systems in low-income and middle-income countries: an overview of systematic reviews.", "What works? Interventions for maternal and child undernutrition and survival.", "Reducing stillbirths: prevention and management of medical disorders and infections during pregnancy.", "A critical appraisal of literature reviews about the transition to adulthood for youth with disabilities.", "Reducing stillbirths: screening and monitoring during pregnancy and labour.", "Tailoring systematic reviews to meet critical priorities in maternal health in the intrapartum period.", "Effects of policy options for human resources for health: an analysis of systematic reviews.", "Increasing the demand for childhood vaccination in developing countries: a systematic review.", "Alma-Ata: Rebirth and Revision 6 Interventions to address maternal, newborn, and child survival: what difference can integrated primary health care strategies make?", "Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions." ]

[ "To explore implications of using systematic drug class reviews to develop U.S. Medicaid drug formularies. We assess racial/ethnic, gender, and socioeconomic status (SES) concordance between Medicaid populations and studies synthesized in Drug Effectiveness Review Project (DERP) systematic reviews.\n Review of 32 DERP systematic reviews for subpopulation reporting/analysis and concordance with Medicaid populations.\n Among Medicaid recipients in DERP member states and nationally, minorities are overrepresented (21% to 57%) compared with their presence in the population (10% to 30%). Fifty-nine percent of DERP reviews reported insufficient evidence to evaluate drug effects by race/ethnicity or gender. Three percent of reviews found evidence of differential effects by race and 13% by gender. Twenty-four percent found evidence of no difference by race and 9% found no difference by gender. Most of this evidence was described as weak, limited, or of poor quality. Eighty percent of Medicaid recipients are poor or near-poor. DERP does not report on SES.\n DERP reviews reveal deficiencies of the evidence when applied to Medicaid populations. To increase health equity and provide evidence for policies that serve socially disadvantaged populations, drug trials, and other studies should include more members of these populations. Systematic reviews should include low-SES as a prespecified subgroup.", "To assess the potential contribution of evidence from existing systematic reviews of effectiveness to answering the question: what works in reducing social inequalities in smoking?\n The Cochrane Library (2002/4).\n Systematic reviews of the effectiveness of community based tobacco control interventions, and all the primary studies included in one of these reviews.\n Reviews and primary studies were assessed for intent to assess the social distribution of intervention effects, information about the social inclusiveness or targeting of interventions, baseline sociodemographic data collected on participants, and estimates of effect size stratified by sociodemographic variables.\n Only one review aimed to examine outcomes stratified by sex, age or socioeconomic status, and these aims were only achieved with respect to sex. Sociodemographic data about participants were frequently collected in primary studies, but not used to compare intervention effects between social groups.\n There may be scope for using existing research more effectively to contribute to evidence based policy to reduce social inequalities in smoking-by explicitly seeking stratified outcome data in new systematic reviews, by re-analysing original datasets, and/or by meta-analysis of individual participant data.", "Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e.g. for drug or alcohol dependency).\n The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis.\n We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e.g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e.g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours.Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities.\n Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed.", "Cardiovascular disease (CVD) is the leading killer of women in the United States, yet medical care is often based on evidence from clinical trials performed predominantly with men. Numerous studies show that CVD risk factors, clinical presentation, treatment, and treatment outcomes can vary between men and women.\n The Cochrane Library maintains a large database of critically appraised evidence including meta-analyses of clinical trials, called Systematic Reviews. There were 30 Systematic Reviews pertaining to the treatment of CVD published collectively by the Cochrane Heart Group, Hypertension Group, and Peripheral Vascular Diseases Groups at the time of our study. We examined these 30 Systematic Reviews and the great majority of the clinical trials used for their meta-analyses for inclusion of women and gender-based data analyses. Women comprised only 27% of the pooled population of 258 clinical trials.\n Of those trials that included both men and women (n = 196), only 33% examined outcomes by gender. In trials that performed a gender-based analysis, 20% reported significant (p < 0.05) differences in cardiovascular-related outcomes by gender.\n We conclude that (1) there are not enough large-scale clinical trials or meta-analyses concerning CVD in women to determine if their medical treatment should differ from that of men, (2) all clinical trials relating to CVD treatment should have significantly more female participants, and gender-based analyses should be performed, as currently recommended for National Institutes of Health (NIH)-sponsored research by the NIH Revitalization Act of 1993, and (3) the Cochrane Library would be a more useful tool for the evidence-based healthcare of women if the Systematic Reviews used all available gender-specific information in their analyses.", "This is the second of five papers in the child survival series. The first focused on continuing high rates of child mortality (over 10 million each year) from preventable causes: diarrhoea, pneumonia, measles, malaria, HIV/AIDS, the underlying cause of undernutrition, and a small group of causes leading to neonatal deaths. We review child survival interventions feasible for delivery at high coverage in low-income settings, and classify these as level 1 (sufficient evidence of effect), level 2 (limited evidence), or level 3 (inadequate evidence). Our results show that at least one level-1 intervention is available for preventing or treating each main cause of death among children younger than 5 years, apart from birth asphyxia, for which a level-2 intervention is available. There is also limited evidence for several other interventions. However, global coverage for most interventions is below 50%. If level 1 or 2 interventions were universally available, 63% of child deaths could be prevented. These findings show that the interventions needed to achieve the millennium development goal of reducing child mortality by two-thirds by 2015 are available, but that they are not being delivered to the mothers and children who need them.", "Tackling health inequalities is high on the political agenda of the Labour government. The government wants to reduce inequalities through policies based on evidence, the health of childbearing women and their babies being priority areas for action. National Service Frameworks (NSFs) are being set up to ensure high quality services for all groups. The External Working Group looking into maternity services for the Children's NSF seeks evidence upon which to plan strategies for all women, while focusing attention on the most disadvantaged. Wide differentials are noted between high- and low-income groups in the outcomes of pregnancy and the health of babies. The worst outcomes appear to be concentrated in small subgroups of disadvantaged women.\n To report on a review of studies of interventions improving perinatal outcomes for disadvantaged women, to inform policy and practice around the organization and delivery of statutory services in the UK.\n We searched six relevant databases for reviews, intervention studies, audits and descriptions of services reporting outcomes for disadvantaged groups of women, published between 1990 and 2003. Synthesis was performed around what works and what does not work. Gaps in the evidence base were identified.\n We found limited evidence of effective and promising interventions for childbearing women from minority ethnic groups, women experiencing domestic violence, women with mental health illness and HIV infected women. Few studies were well-designed or powered to detect effectiveness. There were no studies of interventions for women prisoners, homeless women and travellers.\n Searching for intervention studies primarily by participant subgroup has brought in evidence from few well-designed studies on which to plan policy. Combining this approach with searching for intervention studies addressing behaviour like smoking, and needs like social support, may provide further evidence to tackle inequalities in the perinatal period.", "To determine whether Cochrane Musculoskeletal Group (CMSG) systematic reviews and corresponding primary studies of rheumatoid arthritis interventions report and analyze the data needed to assess the effectiveness of interventions in reducing socioeconomic differences in health and/or improving the health of the poor.\n We selected all CMSG reviews on rheumatoid arthritis published since issue 1, 2003. Fourteen reviews were identified; 147 of the 156 primary studies included in these reviews were obtained and assessed. We extracted data on whether the dimensions place of residence, race/ethnicity/culture, occupation, gender, religion, education, socioeconomic status, and social capital and networks (PROGRESS) were reported or analyzed, and whether any interventions were aimed at disadvantaged or low- and middle-income country populations.\n Among the dimensions of PROGRESS reported at baseline in 147 primary studies, gender (89%) was the most commonly reported, followed by education (25%) and race/ethnicity (18%). Less than 50% of the systematic reviews reported dimensions of PROGRESS even when they had been reported in the primary study. Of 147 primary studies, 6 (5%) were aimed specifically at disadvantaged populations; another 6 reported on effectiveness by at least 1 dimension of PROGRESS.\n Primary studies of interventions for rheumatoid arthritis generally reported few variables necessary to answer questions about health inequalities. Most CMSG systematic reviews failed to assess those variables even when described in the primary studies. The Cochrane Health Equity Field welcomes the opportunity to provide guidance to systematic review authors on incorporating equity considerations into their reviews.", "To examine the use of sex- and gender-based analysis (SGBA) in systematic reviews of cardiovascular health in order to strengthen the evidence base for clinical practice and policy.\n To determine the current status of SGBA in systematic reviews, an appraisal tool was developed by the research team and applied by an independent reviewer to a random sample of 38 Cochrane systematic reviews. The sample was drawn from reviews addressing interventions for cardiovascular diseases (CVD). A random sample of Cochrane reviews in cardiovascular health was selected from the Cochrane Library, Issue 3, 2001, to Issue 3, 2007. The main outcome measure was the number of reviews that included analysis of sex or gender or both.\n Our findings showed that SGBA was generally absent in the sampled reviews. Data were rarely disaggregated by sex; only 2 of 38 reviews reported any sex or gender research gaps. Only one quarter of the reviews included a rationale as to why any subgroup analyses by sex were or were not completed. None of the 38 reviews met all of the appraisal tool criteria. As well, we found that where sex or gender was mentioned, the terms were used interchangeably.\n Despite increasing evidence over the past decade documenting that sex and gender frequently matter in CVD, this study demonstrated that SGBA was rarely considered in systematic reviews. We suggest this omission has important implications for assuring the quality of research and of evidence-based policy and practice and for achieving equitable health outcomes for women and men. To build a robust evidence base for future work in cardiovascular health, we propose that the methodologies of systematic reviews and of SGBA be refined and synchronized to enhance the collection, synthesis, and analysis of evidence for decision making.", "There is increasing pressure to tackle the wider social determinants of health through the implementation of appropriate interventions. However, turning these demands for better evidence about interventions around the social determinants of health into action requires identifying what we already know and highlighting areas for further development.\n Systematic review methodology was used to identify systematic reviews (from 2000 to 2007, developed countries only) that described the health effects of any intervention based on the wider social determinants of health: water and sanitation, agriculture and food, access to health and social care services, unemployment and welfare, working conditions, housing and living environment, education, and transport.\n Thirty systematic reviews were identified. Generally, the effects of interventions on health inequalities were unclear. However, there is suggestive systematic review evidence that certain categories of intervention may impact positively on inequalities or on the health of specific disadvantaged groups, particularly interventions in the fields of housing and the work environment.\n Intervention studies that address inequalities in health are a priority area for future public health research.", "Approximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined.\n We undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies.\n We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact on perinatal mortality. There was limited evidence of impact for maternal hyperoxygenation, and concerns remain about maternal safety. Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies, but a large randomised trial of the intervention had no significant impact on perinatal mortality, suggesting that further studies are needed.\n Although the global appeal to prioritise access to emergency obstetric care, especially vacuum extraction and Caesarean section, rests largely on observational and population-based data, these interventions are clearly life-saving in many cases of fetal compromise. Safe, comprehensive essential and emergency obstetric care is particularly needed, and can make the greatest impact on stillbirth rates, in low-resource settings. Other advanced interventions such as amnioinfusion and hyperoxygenation may reduce perinatal mortality, but concerns about safety and effectiveness require further study before they can be routinely included in programs.", "In this second article of the neonatal survival series, we identify 16 interventions with proven efficacy (implementation under ideal conditions) for neonatal survival and combine them into packages for scaling up in health systems, according to three service delivery modes (outreach, family-community, and facility-based clinical care). All the packages of care are cost effective compared with single interventions. Universal (99%) coverage of these interventions could avert an estimated 41-72% of neonatal deaths worldwide. At 90% coverage, intrapartum and postnatal packages have similar effects on neonatal mortality--two-fold to three-fold greater than that of antenatal care. However, running costs are two-fold higher for intrapartum than for postnatal care. A combination of universal--ie, for all settings--outreach and family-community care at 90% coverage averts 18-37% of neonatal deaths. Most of this benefit is derived from family-community care, and greater effect is seen in settings with very high neonatal mortality. Reductions in neonatal mortality that exceed 50% can be achieved with an integrated, high-coverage programme of universal outreach and family-community care, consisting of 12% and 26%, respectively, of total running costs, plus universal facility-based clinical services, which make up 62% of the total cost. Early success in averting neonatal deaths is possible in settings with high mortality and weak health systems through outreach and family-community care, including health education to improve home-care practices, to create demand for skilled care, and to improve care seeking. Simultaneous expansion of clinical care for babies and mothers is essential to achieve the reduction in neonatal deaths needed to meet the Millennium Development Goal for child survival.", "With smoking increasingly confined to lower socio-economic groups, the tobacco control community has been urged to identify which population-level tobacco control interventions work in order to help tackle smoking-related health inequalities. Systematic reviews have a crucial role to play in this task. This overview was therefore carried out in order to (i) summarise the evidence from existing systematic reviews of population-level tobacco control interventions, and (ii) assess the need for a new systematic review of primary studies, with the aim of assessing the differential effects of such interventions.\n Systematic review methods were used to evaluate existing systematic reviews that assessed a population-level tobacco control intervention and which reported characteristics of included participants in terms of at least one socio-demographic or socio-economic factor.\n Nineteen systematic reviews were included. Four reviews assessed interventions aimed at the population level alone, whilst fifteen included at least one primary study that examined this type of intervention. Four reviews assessed youth access restrictions, one assessed the effects of increasing the unit price of tobacco, and six assessed smoking bans or restrictions. Of the eight remaining reviews, six assessed multi-component community based interventions, in which the population-level interventions were part of a wider tobacco control programme, and two assessed the impact of smoking bans or restrictions in reducing exposure to environmental tobacco smoke. We found tentative evidence that the effect of increasing the unit price of tobacco products may vary between ethnic and socio-economic groups, and between males and females. However, differences in the context and the results of different reviews made it difficult to draw any firm conclusions. Few identified reviews explicitly attempted to examine differences in intervention effects between socio-demographic groups. Therefore on the basis of these reviews the potential for smoking bans, and youth access restrictions to decrease social inequalities in smoking remains unknown.\n There is preliminary evidence that increases in the unit price of tobacco may have the potential to reduce smoking related health inequalities. There is a need for equity effects to be explicitly evaluated in future systematic reviews and in primary research assessing the effects of population tobacco control interventions.", "Depression and anxiety are the most common psychiatric conditions in late life. Despite their prevalence, we know relatively little about their unique manifestation in older adults. And, Although the most common intervention for late-life depression and anxiety continues to be medication, research on psychosocial interventions for late-life depression and anxiety has burgeoned in the past several years. Unfortunately, this growing body of intervention research has yet to be widely translated into improved systems of care for late-life depression. This article is one step toward synthesizing the knowledge in this growing area of research. The review of literature presents the conclusions of several meta-analyses that have reviewed psychosocial interventions for late-life depression and anxiety. In addition, intervention studies concerning the effectiveness of cognitive behavioral therapy, interpersonal therapy, reminiscence therapy, and alternative therapies with depressed and/or anxious older adults are reviewed. A brief description of various approaches to psychosocial intervention with anxious and/or depressed older adults is also presented.", "The vast majority of global stillbirths occur in low- and middle-income countries, and in many settings, the majority of stillbirths occur antenatally, prior to the onset of labour. Poor nutritional status, lack of antenatal care and a number of behaviours increase women's risk of stillbirth in many resource-poor settings. Interventions to reduce these risks could reduce the resulting burden of stillbirths, but the evidence for the impact of such interventions has not yet been comprehensively evaluated.\n This second paper of a systematic review of interventions that could plausibly impact stillbirth rates covers 12 different interventions relating to behavioural and socially mediated risk factors, including exposures to harmful practices and substances, antenatal care utilisation and quality, and maternal nutrition before and during pregnancy. The search strategy reviewed indexed medical journals on PubMed and the Cochrane Library. If any eligible randomised controlled trials were identified that were published after the most recent Cochrane review, they were added to generate new meta-analyses. Interventions covered in this paper have a focus on low- and middle-income countries, both because of the large burden of stillbirths and because of the high prevalence of risk factors including maternal malnutrition and harmful environmental exposures. The reviews and studies belonging to these interventions were graded and conclusions derived about the evidence of benefit of these interventions.\n From a programmatic perspective, none of the interventions achieved clear evidence of benefit. Evidence for some socially mediated risk factors were identified, such as exposure to indoor air pollution and birth spacing, but still require the development of appropriate interventions. There is a need for additional studies on culturally appropriate behavioural interventions and clinical trials to increase smoking cessation and reduce exposure to smokeless tobacco. Balanced protein-energy supplementation was associated with reduced stillbirth rates, but larger well-designed trials are required to confirm findings. Peri-conceptional folic acid supplementation significantly reduces neural tube defects, yet no significant associated reductions in stillbirth rates have been documented. Evidence for other nutritional interventions including multiple micronutrient and Vitamin A supplementation is weak, suggesting the need for further research to assess potential of nutritional interventions to reduce stillbirths.\n Antenatal care is widely used in low- and middle-income countries, and provides a natural facility-based contact through which to provide or educate about many of the interventions we reviewed. The impact of broader socially mediated behaviors, such as fertility decision-making, access to antenatal care, and maternal diet and exposures like tobacco and indoor air pollution during pregnancy, are poorly understood, and further research and appropriate interventions are needed to test the association of these behaviours with stillbirth outcomes. For most nutritional interventions, larger randomised controlled trials are needed which report stillbirths disaggregated from composite perinatal mortality. Many antepartum stillbirths are potentially preventable in low- and middle-income countries, particularly through dietary and environmental improvement, and through improving the quality of antenatal care - particularly including diagnosis and management of high-risk pregnancies - that pregnant women receive.", "There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one-off evaluations rather than impact evaluations with long-term follow-up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high-quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low- and middle-income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC. Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass-media and patient-mediated interventions may change professional practice. Multifaceted interventions that combine several quality-improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration. The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no 'magic bullets' or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision-makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality-improvement activities, priority setting, selection and design of interventions, and evaluation.", "The prevalence of mental health problems, some of which seem to be occurring among younger cohorts, leads researchers and policy-makers to search for practical solutions to reduce the burden of suffering on children and their families, and the costs to society both immediate and long term. Numerous programs are in place to reduce or alleviate problem behaviour or disorders and/or assist positive youth development. Evaluated results are dispersed throughout the literature. To assess findings and determine common elements of effective children's services, a literature search was undertaken for evidence-based evaluations of non-clinical programs for school-age children. Prescriptive comments aim to inform service-providers, policy-makers and families about best practices for effective services such as: early, long-term intervention including reinforcement, follow-up and an ecological focus with family and community sector involvement; consistent adult staffing; and interactive, non-didactic programming adapted to gender, age and cultural needs. Gaps are identified in our understanding of efficiencies that result from effective programs. Policy implications include the need to develop strategies for intersectoral interventions, including: new financing arrangements to encourage (not penalize) interagency cooperation and, to ensure services reach appropriate segments of the population; replication of best practices; and publicizing information about benefits and cost savings. In many jurisdictions legislative changes could create incentives for services to collaborate on service delivery. Joint decision-making would require intersectoral governance, pooling of some funding, and policy changes to retain savings at the local level. Savings could finance expansion of services for additional youth.", "Strengthening health systems is a key challenge to improving the delivery of cost-effective interventions in primary health care and achieving the vision of the Alma-Ata Declaration. Effective governance, financial and delivery arrangements within health systems, and effective implementation strategies are needed urgently in low-income and middle-income countries. This overview summarises the evidence from systematic reviews of health systems arrangements and implementation strategies, with a particular focus on evidence relevant to primary health care in such settings. Although evidence is sparse, there are several promising health systems arrangements and implementation strategies for strengthening primary health care. However, their introduction must be accompanied by rigorous evaluations. The evidence base needs urgently to be strengthened, synthesised, and taken into account in policy and practice, particularly for the benefit of those who have been excluded from the health care advances of recent decades.", "We reviewed interventions that affect maternal and child undernutrition and nutrition-related outcomes. These interventions included promotion of breastfeeding; strategies to promote complementary feeding, with or without provision of food supplements; micronutrient interventions; general supportive strategies to improve family and community nutrition; and reduction of disease burden (promotion of handwashing and strategies to reduce the burden of malaria in pregnancy). We showed that although strategies for breastfeeding promotion have a large effect on survival, their effect on stunting is small. In populations with sufficient food, education about complementary feeding increased height-for-age Z score by 0.25 (95% CI 0.01-0.49), whereas provision of food supplements (with or without education) in populations with insufficient food increased the height-for-age Z score by 0.41 (0.05-0.76). Management of severe acute malnutrition according to WHO guidelines reduced the case-fatality rate by 55% (risk ratio 0.45, 0.32-0.62), and recent studies suggest that newer commodities, such as ready-to-use therapeutic foods, can be used to manage severe acute malnutrition in community settings. Effective micronutrient interventions for pregnant women included supplementation with iron folate (which increased haemoglobin at term by 12 g/L, 2.93-21.07) and micronutrients (which reduced the risk of low birthweight at term by 16% (relative risk 0.84, 0.74-0.95). Recommended micronutrient interventions for children included strategies for supplementation of vitamin A (in the neonatal period and late infancy), preventive zinc supplements, iron supplements for children in areas where malaria is not endemic, and universal promotion of iodised salt. We used a cohort model to assess the potential effect of these interventions on mothers and children in the 36 countries that have 90% of children with stunted linear growth. The model showed that existing interventions that were designed to improve nutrition and prevent related disease could reduce stunting at 36 months by 36%; mortality between birth and 36 months by about 25%; and disability-adjusted life-years associated with stunting, severe wasting, intrauterine growth restriction, and micronutrient deficiencies by about 25%. To eliminate stunting in the longer term, these interventions should be supplemented by improvements in the underlying determinants of undernutrition, such as poverty, poor education, disease burden, and lack of women's empowerment.", "An estimated two-thirds of the world's 3.2 million stillbirths occur antenatally, prior to labour, and are often overlooked in policy and programs. Poorly recognised, untreated or inadequately treated maternal infections such as syphilis and malaria, and maternal conditions including hypertensive disorders, are known risk factors for stillbirth.\n We undertook a systematic review of the evidence for 16 antenatal interventions with the potential to prevent stillbirths. We searched a range of sources including PubMed and the Cochrane Library. For interventions with prior Cochrane reviews, we conducted additional meta-analyses including eligible newer randomised controlled trials following the Cochrane protocol. We focused on interventions deliverable at the community level in low-/middle-income countries, where the burden of stillbirths is greatest.\n Few of the studies we included reported stillbirth as an outcome; most that did were underpowered to assess this outcome. While Cochrane reviews or meta-analyses were available for many interventions, few focused on stillbirth or perinatal mortality as outcomes, and evidence was frequently conflicting. Several interventions showed clear evidence of impact on stillbirths, including heparin therapy for certain maternal indications; syphilis screening and treatment; and insecticide-treated bed nets for prevention of malaria. Other interventions, such as management of obstetric intrahepatic cholestasis, maternal anti-helminthic treatment, and intermittent preventive treatment of malaria, showed promising impact on stillbirth rates but require confirmatory studies. Several interventions reduced known risk factors for stillbirth (e.g., anti-hypertensive drugs for chronic hypertension), yet failed to show statistically significant impact on stillbirth or perinatal mortality rates. Periodontal disease emerged as a clear risk factor for stillbirth but no interventions have reduced stillbirth rates.\n Evidence for some newly recognised risk factors for stillbirth, including periodontal disease, suggests the need for large, appropriately designed randomised trials to test whether intervention can minimise these risks and prevent stillbirths. Existing evidence strongly supports infection control measures, including syphilis screening and treatment and malaria prophylaxis in endemic areas, for preventing antepartum stillbirths. These interventions should be incorporated into antenatal care programs based on attributable risks and burden of disease.", "A critical appraisal of five review articles on the transition to adulthood for youth with disabilities was conducted to identify evidence about (1) the factors that help or hinder the transition process, and (2) \"what's working\" in transition services. The appraisal identified a number of important \"success\" factors and elements of service delivery that are worthy of consideration by service providers and researchers. These include the need for skill development of youth with disabilities, environmental supports, and an individualized approach to service delivery. All of the reviews identified the need for more evidence to support the implementation and evaluation of best practice models/approaches that address the complex issue of the transition from paediatric to adult services for youth with disabilities.", "Screening and monitoring in pregnancy are strategies used by healthcare providers to identify high-risk pregnancies so that they can provide more targeted and appropriate treatment and follow-up care, and to monitor fetal well-being in both low- and high-risk pregnancies. The use of many of these techniques is controversial and their ability to detect fetal compromise often unknown. Theoretically, appropriate management of maternal and fetal risk factors and complications that are detected in pregnancy and labour could prevent a large proportion of the world's 3.2 million estimated annual stillbirths, as well as minimise maternal and neonatal morbidity and mortality.\n The fourth in a series of papers assessing the evidence base for prevention of stillbirths, this paper reviews available published evidence for the impact of 14 screening and monitoring interventions in pregnancy on stillbirth, including identification and management of high-risk pregnancies, advanced monitoring techniques, and monitoring of labour. Using broad and specific strategies to search PubMed and the Cochrane Library, we identified 221 relevant reviews and studies testing screening and monitoring interventions during the antenatal and intrapartum periods and reporting stillbirth or perinatal mortality as an outcome.\n We found a dearth of rigorous evidence of direct impact of any of these screening procedures and interventions on stillbirth incidence. Observational studies testing some interventions, including fetal movement monitoring and Doppler monitoring, showed some evidence of impact on stillbirths in selected high-risk populations, but require larger rigourous trials to confirm impact. Other interventions, such as amniotic fluid assessment for oligohydramnios, appear predictive of stillbirth risk, but studies are lacking which assess the impact on perinatal mortality of subsequent intervention based on test findings. Few rigorous studies of cardiotocography have reported stillbirth outcomes, but steep declines in stillbirth rates have been observed in high-income settings such as the U.S., where cardiotocography is used in conjunction with Caesarean section for fetal distress.\n There are numerous research gaps and large, adequately controlled trials are still needed for most of the interventions we considered. The impact of monitoring interventions on stillbirth relies on use of effective and timely intervention should problems be detected. Numerous studies indicated that positive tests were associated with increased perinatal mortality, but while some tests had good sensitivity in detecting distress, false-positive rates were high for most tests, and questions remain about optimal timing, frequency, and implications of testing. Few studies included assessments of impact of subsequent intervention needed before recommending particular monitoring strategies as a means to decrease stillbirth incidence. In high-income countries such as the US, observational evidence suggests that widespread use of cardiotocography with Caesarean section for fetal distress has led to significant declines in stillbirth rates. Efforts to increase availability of Caesarean section in low-/middle-income countries should be coupled with intrapartum monitoring technologies where resources and provider skills permit.", "Health care practitioners and researchers commonly call for greater reliance on evidence as a means to achieve improvement in quality of care. Systematic reviews provide a means to accelerate the use of evidence-based clinical interventions and public health practices. The extent to which these time- and resource-intensive systematic reviews currently address critical maternal health priorities in the intrapartum period is unclear. This analysis summarises key maternal health and research priorities, maps these priorities to existing reviews, identifies gaps in the literature that can be addressed with systematic reviews, and highlights key methodological concerns in conducting systematic reviews. The analysis draws on published data on maternal morbidities and an overview of 108 systematic reviews in Medline in the past 5 years using the MeSH terms 'Delivery, Obstetric,' to draw the links between health priorities, research priorities, existing evidence and missing evidence. Key causes of morbidity during labour and delivery in the United States include haemorrhage, pre-eclampsia and eclampsia, obstetric trauma and infection. Analyses of maternal morbidity and mortality suggest that key concerns include racial and ethnic disparities in health outcomes and the prevention of adverse events. Systematic reviews, however, generally tend to focus on the reduction of harms associated with interventions, are frequently limited to randomised designs, and do not address issues of health disparities. The results suggest that advances in evidence-based care in maternal health require that systematic reviews address issues of prevention of adverse events, include a larger variety of study designs when necessary and pay closer attention to health disparities.", "Policy makers face challenges to ensure an appropriate supply and distribution of trained health workers and to manage their performance in delivery of services, especially in countries with low and middle incomes. We aimed to identify all available policy options to address human resources for health in such countries, and to assess the effectiveness of these policy options.\n We searched Medline and Embase from 1979 to September, 2006, the Cochrane Library, and the Human Resources for Health Global Resource Center database. We also searched up to 10 years of archives from five relevant journals, and consulted experts. We included systematic reviews in English which assessed the effects of policy options that could affect the training, distribution, regulation, financing, management, organisation, or performance of health workers. Two reviewers independently assessed each review for eligibility and quality, and systematically extracted data about main effects. We also assessed whether the policy options were equitable in their effects; suitable for scaling up; and applicable to countries with low and middle incomes.\n 28 of the 759 systematic reviews of effects that we identified were eligible according to our criteria. Of these, only a few included studies from countries with low and middle incomes, and some reviews were of low quality. Most evidence focused on organisational mechanisms for human resources, such as substitution or shifting tasks between different types of health workers, or extension of their roles; performance-enhancing strategies such as quality improvement or continuing education strategies; promotion of teamwork; and changes to workflow. Of all policy options, the use of lay health workers had the greatest proportion of reviews in countries with a range of incomes, from high to low.\n We have identified a need for more systematic reviews on the effects of policy options to improve human resources for health in countries with low and middle incomes, for assessments of any interventions that policy makers introduce to plan and manage human resources for health, and for other research to aid policy makers in these countries.", "Attempts to maintain or increase vaccination coverage almost all focus on supply side interventions: improving availability and delivery of vaccines. The effectiveness and cost-effectiveness of efforts to increase demand is uncertain.\n We performed a systematic review of studies that provided quantitative estimates of the impact of demand side interventions on uptake of routine childhood vaccination. We retrieved studies published up to Sept 2008.\n The initial search retrieved 468 potentially eligible studies, including four systematic reviews and eight original studies of the impact of interventions to increase demand for vaccination. We identified only two randomised controlled trials. Interventions with an impact on vaccination uptake included knowledge translation (KT) (mass media, village resource rooms and community discussions) and non-KT initiatives (incentives, economic empowerment, household visits by extension workers). Most claimed to increase vaccine coverage by 20 to 30%. Estimates of the cost per vaccinated child varied considerably with several in the range of $10-20 per vaccinated child.\n Most studies reviewed here represented a low level of evidence. Mass media campaigns may be effective, but the impact depends on access to media and may be costly if run at a local level. The persistence of positive effects has not been investigated. The economics of demand side interventions have not been adequately assessed, but available data suggest that some may be very cost-effective.", "Several recent reviews of maternal, newborn, and child health (MNCH) and mortality have emphasised that a large range of interventions are available with the potential to reduce deaths and disability. The emphasis within MNCH varies, with skilled care at facility levels recommended for saving maternal lives and scale-up of community and household care for improving newborn and child survival. Systematic review of new evidence on potentially useful interventions and delivery strategies identifies 37 key promotional, preventive, and treatment interventions and strategies for delivery in primary health care. Some are especially suitable for delivery through community support groups and health workers, whereas others can only be delivered by linking community-based strategies with functional first-level referral facilities. Case studies of MNCH indicators in Pakistan and Uganda show how primary health-care interventions can be used effectively. Inclusion of evidence-based interventions in MNCH programmes in primary health care at pragmatic coverage in these two countries could prevent 20-30% of all maternal deaths (up to 32% with capability for caesarean section at first-level facilities), 20-21% of newborn deaths, and 29-40% of all postneonatal deaths in children aged less than 5 years. Strengthening MNCH at the primary health-care level should be a priority for countries to reach their Millennium Development Goal targets for reducing maternal and child mortality.", "Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs).\n Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria.\n Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: Two interventions prevent preterm births--smoking cessation and progesterone. Eight interventions prevent stillbirths--balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery. Eleven interventions improve survival of preterm newborns--prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome\n The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions." ]

[ "327645", "788451", "162675", "7025555", "1096611" ]

[ "[Primary dysmenorrhea. Severe primary dysmenorrhea treated with the selective beta-adrenergic stimulating agent ritodrine chloride].", "The use of isoxsuprine in essential dysmenorrhea. A controlled clinical study.", "Isoxsuprine in primary dysmenorrhoea. Its effectiveness in premenstrual tension.", "Terbutaline inhalation for alleviation of severe pain in essential dysmenorrhea.", "Beta-receptor stimulation in essential dysmenorrhea." ]

[ "nan", "The \"uterus-specific\" beta-adrenoceptor stimulator isoxsuprine was used for the treatment of primary dysmenorrhea in a double-blind controlled clinical study. No significant beneficial effect of the drug was evident.", "The drug combination including isoxsuprine 10 mg, acetaminophen 250 mg and caffeine 30 mg was administered to 80 patients divided into two groups, 40 with premenstrual tension and 40 with clinically diagnosed primary dysmenorrhoea. The study was carried out by the double-blind method and the patients were distributed at random. The results obtained show an excellent or very good response in 95% of cases of premenstrual tension and in 92.5% of cases of dysmenorrhoea. When the overall effectiveness of the compound in both conditions is considered, we find it to be 93.75%. A general discussion of the findings is presented in relation to age, civil status, time of appearance of dysmenorrhoea, nature of pain, accompanying symptoms, previous treatment, other non-drug therapies, results obtained, time within which symptoms were alleviated, total dose of the drug and side-effects. It is concluded that the orally-administered therapeutic combination is effective in both dysmenorrhoea and premenstrual tension.", "In a double-blind cross-over study the effect of terbutaline spray (Bricanyl aerosol) inhalations was tested in 14 women with severe dysmenorrhea. A significant relief was noted in association with an increased menstrual blood loss. The side effects were few.", "nan" ]

[ "7672875", "3287907" ]

[ "Evaluation of piroxicam-beta-cyclodextrin, piroxicam, paracetamol and placebo in post-operative oral surgery pain.", "Analgesic efficacy of piroxicam in the treatment of postoperative pain." ]

[ "Two hundred ninety-eight patients with post-operative pain after the surgical removal of an impacted third molar were randomly assigned, on a double-blind basis, to receive a single oral dose of piroxicam 20 mg, or piroxicam-beta-cyclodextrin equivalent to 20 mg piroxicam, or paracetamol 500 mg, or placebo. Using a semi-quantitative self-rating scale, patients rated their pain and its relief at 30-min intervals for the first 2 h, and then hourly for 4 h after treatment administration. All active medications were reported to be significantly superior to placebo. The three active drugs were comparable for the degree of analgesia up to the third hour, after which the effect of paracetamol decreased significantly as compared to piroxicam-beta-cyclodextrin and piroxicam. Piroxicam-beta-cyclodextrin and paracetamol were more rapid than piroxicam in inducing analgesia. The tolerability for the active drugs was comparable to that for placebo.", "Two randomized, double-blind, single-dose studies were conducted to assess the analgesic efficacy and safety of piroxicam for the treatment of moderate or severe postoperative pain. Study 1 evaluated the analgesic efficacy of piroxicam 20 mg compared with that of codeine sulfate 60 mg and placebo. A final patient population of 149 subjects rated pain intensity and pain relief at one half hour and one hour following treatment and then hourly for six hours, with a global assessment made at the completion of 24 hours. Piroxicam 20 mg was significantly more efficacious than placebo for all analgesic variables, including the sum of the pain intensity differences (SPID), total pain relief (TOTAL), percent SPID, duration of effect, and time to remedication. Codeine 60 mg was significantly superior to placebo for percent SPID and some hourly measures. Piroxicam 20 mg was significantly more effective than codeine 60 mg for percent SPID and a few hourly measures including time to remedication. Study 2 assessed the efficacy of piroxicam 20 mg or 40 mg compared with aspirin 648 mg and placebo. Sixty patients rated their pain intensity and relief hourly for 12 hours and at 24 hours after administration of study medication. Both doses of piroxicam were significantly more effective than placebo from Hours 2 to 12 for pain intensity difference (PID) and relief scores, as well as for SPID and TOTAL. Aspirin was significantly more effective than placebo from Hours 2 to 8 for relief and Hours 2 to 10 for PID as well as SPID and TOTAL. Piroxicam 40 mg was significantly more effective than aspirin 648 mg for SPID, TOTAL, and hourly measures beginning with Hour 6 through Hour 12. Piroxicam 20 mg was significantly better than aspirin for a few hourly measures: Hours 7 to 9 for relief and Hour 7 for PID. In addition, effects of piroxicam 20 mg had a significantly longer duration than aspirin. Similarly, piroxicam 20 mg had a significantly longer time to remedication compared with aspirin and placebo. The results of these studies provide evidence in support of the longer duration of analgesic efficacy of piroxicam compared with codeine or aspirin in patients with postoperative pain." ]

[ "16291160" ]

[ "A randomized controlled trial of elective preterm delivery of fetuses with gastroschisis." ]

[ "Elective preterm delivery of the fetus with gastroschisis may help to limit injury to the extruded fetal gut and thus promote faster recovery of neonatal gut function and earlier hospital discharge. This hypothesis has not previously been tested in a prospective randomized controlled trial.\n Between May 1995 and September 1999, all women referred to a single tertiary center before 34 weeks' gestation with a sonographically diagnosed fetal gastroschisis were invited to participate in a randomized controlled trial. Eligible patients were randomized to elective delivery at 36 weeks or to await the onset of spontaneous labor. The method of delivery was not prescribed by the trial. Primary outcome measures in the neonate were the time taken to tolerate full enteral feeding (150 mL/kg per day) and duration of hospital stay.\n Of 44 eligible women, 42 were randomized, 21 to elective delivery and 21 to await spontaneous labor. There were 20 liveborn infants in each group. Four babies in the elective group and 4 in the spontaneous group delivered before 36 weeks' gestation but were included in the analysis on an intention-to-treat basis. Mean gestational age at delivery was 35.8 weeks in the elective group and 36.7 weeks in the spontaneous group. Primary closure of the gastroschisis was achieved in a similar proportion (80%-85%) of infants in both groups. Two babies in the elective group died from short gut complications. In the survivors, there was a trend in favor of a shorter median time to achieve full enteral feeding (30.5 vs 37.5 days) and a shorter median duration of hospital stay (47.5 vs 53 days) in the elective group, but this was not statistically significant. These findings remained unaltered when the data were reanalyzed after (a) excluding infants with intestinal atresia or (b) excluding infants born before 36 weeks' gestation.\n Although limited by the small number of patients, this randomized controlled trial demonstrates no significant benefit from elective preterm delivery of fetuses with gastroschisis." ]

[ "8457023" ]

[ "Selenium supplementation in intrinsic asthma." ]

[ "The accumulated data indicate that asthma is associated with reduced circulatory selenium (Se) status and lowered activity of the Se-dependent enzyme glutathione peroxidase (GSH-Px), which may have etiological implications, considering the important role of GSH-Px in the cellular elimination of hydroperoxides. The aim of the present double-blind study was to investigate whether Se supplementation in asthmatic patients may increase GSH-Px activity and possibly bring about clinical improvement. Twenty-four patients suffering from intrinsic asthma were selected and randomized into two groups, and after a preintervention period of 4 weeks, one group received a daily supplement of 100 micrograms sodium selenite for 14 weeks, whereas the other group received placebo. In the Se-supplemented group there were significant increases in serum Se and platelet GSH-Px activity after intervention, accompanied by a significant reduction in the irreversible platelet aggregation induced by 5 mumol/l ADP, while no significant changes in these parameters could be observed in the placebo group. Further, there was a significant clinical improvement in the Se-supplemented group, as compared with the placebo group, with regard to the assembled clinical evaluation made of each patient. This improvement could, however, not be validated by significant changes in the separate clinical parameters of lung function and airway hyperresponsiveness. The results are discussed in view of the role of GSH-Px in the cellular enzymatic oxidant defense system and as a modulator of arachidonic acid metabolism." ]

[ "14638885", "16403993", "7611638", "17502549", "16713921", "12554382", "10522877", "16175627", "12635120", "17222115", "7611639", "9365349" ]

[ "Pyridostigmine in postpolio syndrome: no decline in fatigue and limited functional improvement.", "Effects of lamotrigine on the symptoms and life qualities of patients with post polio syndrome: a randomized, controlled study.", "A double-blind, placebo-controlled trial of amantadine for the treatment of fatigue in patients with the post-polio syndrome.", "Modafinil for treatment of fatigue in post-polio syndrome: a randomized controlled trial.", "Intravenous immunoglobulin for post-polio syndrome: a randomised controlled trial.", "Treatment of patients with postpolio syndrome in a warm climate.", "A multicenter, randomized, double-blinded trial of pyridostigmine in postpolio syndrome.", "Randomized controlled trial of modafinil for the treatment of fatigue in postpolio patients.", "Randomized controlled trial of strength training in post-polio patients.", "Post-polio syndrome patients treated with intravenous immunoglobulin: a double-blinded randomized controlled pilot study.", "A double-blind, placebo-controlled trial of high-dose prednisone for the treatment of post-poliomyelitis syndrome.", "Response of pain to static magnetic fields in postpolio patients: a double-blind pilot study." ]

[ "To investigate the effect of pyridostigmine on fatigue, physical performance, and muscle function in subjects with postpoliomyelitis syndrome.\n 67 subjects with increased fatigue and new weakness in one quadriceps muscle showing neuromuscular transmission defects, were included in a randomised, double blind, placebo controlled trial of 60 mg pyridostigmine four times a day for 14 weeks. Primary outcome was fatigue (on the \"energy\" category of the Nottingham health profile). Secondary outcomes included two minute walking distance and quadriceps strength and jitter. Motor unit size of the quadriceps was studied as a potential effect modifier. The primary data analysis compared the changes from baseline in the outcomes in the last week of treatment between groups.\n 31 subjects treated with pyridostigmine and 31 subjects treated with placebo completed the trial. No significant effect of pyridostigmine was found on fatigue. The walking distance improved more in the pyridostigmine group than in the placebo group (by 7.2 m (6.0%); p<0.01). Subgroup analysis showed that a significant improvement in walking performance was only found in subjects with normal sized motor units. Quadriceps strength improved more in the pyridostigmine group than in the placebo group (by 6.7 Nm (7.2%); p = 0.15). No effect of pyridostigmine was found on jitter.\n Pyridostigmine in the prescribed dose did not reduce fatigue in subjects with postpoliomyelitis syndrome. However, it may have a limited beneficial effect on physical performance, especially in subjects with neuromuscular transmission defects in normal sized motor units.", "The aim of this study is to find out if lamotrigine gives symptomatic relief and enhances quality of life in patients with post-polio syndrome. Thirty patients were randomly assigned to receive or not to receive lamotrigine treatment. Lamotrigine at a daily dose of 50-100 mg was given to the fifteen patients, and fifteen patients were used as the control group. Interventional advice and home exercises were given to all of the patients. Clinical assessments were made at baseline and repeated at the second and fourth weeks by the physician who was unaware of medication. The severity of pain, fatigue and muscle cramps were rated on a visual analogue scale. Health-related quality of life was measured using the Nottingham Health Profile. The patient's perceived level of fatigue was assessed using Fatigue Severity Scale. Comparing to the baseline values, statistically significant improvements were obtained in the mean scores of VAS, NHP and FSS at two weeks and four weeks in the patients on lamotrigine. No significant improvements were reported in the control group. These preliminary results indicate that lamotrigine relieves the symptoms and improves the life qualities of patients with post polio syndrome.", "Because amantadine has been shown to reduce fatigue in patients with multiple sclerosis, we performed a double-blind, placebo-controlled study to assess its efficacy in the disabling symptom of post-polio fatigue. Twenty-three patients completed six weeks of therapy. Fatigue was measured by the patients using visual analogue scales (twice per day) and numerical fatigue severity scales (once per week) and by overall impression (at end of therapy). Formal neuropsychological testing and serum drug levels were performed to assess compliance. On all measures, no significant difference was found between treatment and placebo groups. Fifty-four percent of patients given amantadine and 43% given placebo reported a decrease in fatigue; however, the visual analogue scales and fatigue severity scales failed to reflect any improvement. Several patients in the treatment group elected to continue amantadine therapy after the study was completed. Our findings suggest that amantadine is not significantly better than placebo in reducing the sensation of fatigue in post-polio syndrome, and that the measures we employed were insensitive to capture the subjective response experienced by a few patients.", "To determine if modafinil can improve fatigue in patients with post-polio syndrome.\n We used a randomized, placebo-controlled crossover trial. Intervention with modafinil (400 mg/day) and placebo occurred over 6-week periods. Primary endpoint (fatigue) was assessed using the Fatigue Severity Scale as the main outcome measure. Other measures included the Visual Analog Scale for Fatigue and the Fatigue Impact Scale. Secondary endpoint (health-related quality of life) was assessed using the 36-Item Short-Form. Analysis of variance for repeated measures was applied to assess treatment, period, and carryover effects.\n Thirty-six patients were randomized, 33 of whom (mean age: 61 years) completed required interventions. Treatment with modafinil was safe and well-tolerated. After adjusting for periods and order effects, no difference was observed between treatments.\n Based on the utilized measures of outcome modafinil was not superior to placebo in alleviating fatigue or improving quality of life in the studied post-polio syndrome population.", "Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, known as post-polio syndrome. Production of proinflammatory cytokines within the CNS indicates an underlying inflammatory process, accessible for immunomodulatory treatment. We did a multicentre, randomised, double-blind, placebo-controlled study of intravenous immunoglobulin in post-polio syndrome.\n 142 patients at four university clinics were randomly assigned infusion of either 90 g in total of intravenous immunoglobulin (n=73) or placebo (n=69) during 3 consecutive days, repeated after 3 months. Seven patients were withdrawn from the study. Thus, 135 patients were assessed per protocol. Primary endpoints were muscle strength in a selected study muscle and quality of life as measured with the SF-36 questionnaire (SF-36 PCS). Secondary endpoints were 6-minute walk test (6MWT), timed up and go (TUG), muscle strength in muscles not chosen as the study muscle, physical activity scale of the elderly (PASE), visual analogue scale (VAS) for pain, multidimensional fatigue inventory (MFI-20), balance, and sleep quality. Outcome tests were done immediately before the first infusion and 3 months after the second infusion. This study is registered with , number NCT00160082.\n Compared with baseline, median muscle strength differed by 8.3% between patients receiving intravenous immunoglobulin and placebo, in favour of the treatment group (p=0.029). SF-36 PCS did not differ significantly between the groups after treatment (p=0.321). Differences in the subscale vitality score (p=0.042) and PASE (p=0.018) favoured the active treatment group. MFI-20, TUG, muscle strength in the muscles not chosen as the study muscle, 6MWT, balance, and sleep quality did not differ between groups. For the whole study population there was no significant change in pain, as determined by VAS. Nevertheless, patients who reported pain at the study start improved in the intervention group but not in the placebo group (p=0.037). Intravenous immunoglobulin was well tolerated.\n Intravenous immunoglobulin could be a supportive treatment option for subgroups of patients with post-polio syndrome. Further studies on responding subgroups, long-term effects, and dosing schedules are needed.", "Treatment in warm climate of various patient groups including patients with postpolio syndrome is controversial.\n Eighty-eight patients with postpolio syndrome (61 women) were recruited, stratified according to sex, age (above/below 60 years old) and use/not use of electrical wheelchair, and randomized to three groups. Group 1 (n=30) underwent treatment in a rehabilitation centre in Tenerife for four weeks in November/December 1999. Group 2 (n=29) were treated in two similar centres in Norway for the same period of time, while Group 3 (n=29), the control group, followed their ordinary health care programme. All patients were tested at the start of study, and 3 and 6 months later, including physical tests and several questionnaire and qualitative interviews. Patients in Group 1 and 2 were also tested after the rehabilitation period.\n Group 1 and 2 improved significantly both in physical tests and subjective ratings. The positive effects in Group 1 tended to exceed the positive effects in Group 2, and the effects lasted longer. Six minutes walking distance in the two groups was 347 m and 316 m, respectively, before the treatment period, 429 m and 362 m immediately after, and 431 m and 356 m 3 months later. Subjective rating of pain (VAS-scale) was 42 and 43, respectively, before treatment, 17 and 31 immediately after, and 28 and 44 3-months later. In the control group, only minor changes were found.\n The study seems to document a positive effect of treatment of patients with postpolio syndrome in warm climate.", "Postpoliomyelitis syndrome (PPS) is likely due to degeneration and dysfunction of terminal axons of enlarged postpolio motor units. Age-related decline in growth hormone and insulin-like growth factor (IGF-I) may be a contributing factor. Neuromuscular junction abnormalities and decreased IGF-I levels may respond to the anticholinesterase pyridostigmine, with consequent improvement in strength, fatigue, and quality of life.\n To determine the effect of pyridostigmine in PPS on health-related quality of life, isometric muscle strength, fatigue, and serum IGF-I levels; and to assess the safety of pyridostigmine in PPS.\n The study was a multicenter, randomized, double-blinded, placebo-controlled trial of a 6-month course of pyridostigmine 60 mg three times per day in 126 PPS patients. The primary data analysis compared mean changes of outcomes between treatment and control groups at 6 months using an intention to treat approach. Secondary analyses included a comparison of outcomes at 6 and 10 weeks, and in compliant patients.\n The study showed no significant differences in pyridostigmine and placebo-treated patients with regard to changes in quality of life, isometric strength, fatigue, and IGF-I serum levels at 6 months in the primary analysis and in compliant patients. There were no differences in outcomes at 6 and 10 weeks between groups. However, very weak muscles (1 to 25% predicted normal at baseline) were somewhat stronger (p = 0.10, 95% CI of difference -9.5 to 73.3%), and in compliant patients IGF-I was somewhat increased (p = 0.15, 95% CI of difference -6.4 to 44.8 ng/mL) at 6 months with the medication. Pyridostigmine was generally well tolerated.\n This study showed no significant differences between pyridostigmine and placebo-treated PPS patients on measures of quality of life, isometric strength, fatigue, and serum IGF-I.", "The purpose of this study was to test whether modafinil is effective in alleviating the symptoms of fatigue in postpolio patients, because it has been helpful for such symptoms in other neurologic disorders. Using a double-blind, randomized, placebo-controlled cross-over design, 14 postpolio patients with moderate to severe fatigue were assigned to receive modafinil or placebo first. Piper Fatigue Scale, Epworth Sleepiness Scale, digit span, and reaction time tests were done at baseline and then at weekly intervals. The Piper Fatigue Scale scores improved by 27 +/- 40% (mean +/- SD) following modafinil and by 43 +/- 36% following placebo. Scores for most of the other tests did not change during the study. Therefore, we conclude that modafinil was not effective in alleviating the symptoms of fatigue in postpolio patients.", "Many post-polio patients develop new muscle weakness decades after the initial illness. However, its mechanism and treatment are controversial. The purpose of this study was to test the hypotheses that: (1) after strength training, post-polio patients show strength improvement comparable to that seen in the healthy elderly; (2) such training does not have a deleterious effect on motor unit (MU) survival; and (3) part of the strength improvement is due to an increase in voluntary motor drive. After baseline measures including maximum voluntary contraction force, voluntary activation index, motor unit number estimate, and the tetanic tension of the thumb muscles had been determined, 10 post-polio patients with hand involvement were randomized to either the training or control group. The progressive resistance training program consisted of three sets of eight isometric contractions, three times weekly for 12 weeks. Seven healthy elderly were also randomized and trained in a similar manner. Changes in the baseline parameters were monitored once every 4 weeks throughout the training period. The trained post-polio patients showed a significant improvement in their strength (P < 0.05). The magnitude of gain was greater than that seen in the healthy elderly (mean +/- SE, 41 +/- 16% vs. 29 +/- 8%). The training did not adversely affect MU survival and the improvement was largely attributable to an increase in voluntary motor drive. We therefore conclude that moderate intensity strength training is safe and effective in post-polio patients.", "Post-polio syndrome (PPS) is characterized by new muscle weakness, atrophy, fatigue and pain developing several years after the acute polio. Some studies suggest an ongoing inflammation in the spinal cord in these patients. From this perspective, intravenous immunoglobulin (IvIg) could be a therapeutic option. We performed a double-blinded randomized controlled pilot study with 20 patients to investigate the possible clinical effects of IvIg in PPS. Twenty patients were randomized to either IvIg 2 g/kg body weight or placebo. Primary endpoints were changes in pain, fatigue and muscle strength 3 months after treatment. Surrogate endpoints were changes in cerebrospinal fluid (CSF) cytokine levels. Secondary endpoints were pain, fatigue and isometric muscle strength after 6 months. Patients receiving IvIg reported a significant improvement in pain during the first 3 months, but no change was noted for subjective fatigue and muscle strength. CSF levels of tumour necrosis factor-alpha (TNF-alpha) were increased compared with patients with non-inflammatory neurological disorders. In conclusion, in this small pilot study no effect was seen with IvIg treatment on muscle strength and fatigue, however IvIg treated PPS patients reported significantly less pain 3 months after treatment. TNF-alpha was increased in the CSF from PPS patients. The results are promising, but not conclusive because of the low number of patients studied.", "nan", "To determine if the chronic pain frequently presented by postpolio patients can be relieved by application of magnetic fields applied directly over an identified pain trigger point.\n Double-blind randomized clinical trial.\n The postpolio clinic of a large rehabilitation hospital.\n Fifty patients with diagnosed postpolio syndrome who reported muscular or arthritic-like pain.\n Application of active or placebo 300 to 500 Gauss magnetic devices to the affected area for 45 minutes.\n Score on the McGill Pain Questionnaire.\n Patients who received the active device experienced an average pain score decrease of 4.4 +/- 3.1 (p < .0001) on a 10-point scale. Those with the placebo devices experienced a decrease of 1.1 +/- 1.6 points (p < .005). The proportion of patients in the active-device group who reported a pain score decrease greater than the average placebo effect was 76%, compared with 19% in the placebo-device group (p < .0001).\n The application of a device delivering static magnetic fields of 300 to 500 Gauss over a pain trigger point results in significant and prompt relief of pain in postpolio subjects." ]

[ "15964483", "11747915", "8817830", "11170991", "16338450", "8147091", "2119897", "15526058" ]

[ "Safety and immunogenicty of RTS,S/AS02A candidate malaria vaccine in Gambian children.", "Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial.", "Plasmodium falciparum circumsporozoite vaccine immunogenicity and efficacy trial with natural challenge quantitation in an area of endemic human malaria of Kenya.", "Efficacy of recombinant circumsporozoite protein vaccine regimens against experimental Plasmodium falciparum malaria.", "Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial.", "Safety, immunogenicity and limited efficacy study of a recombinant Plasmodium falciparum circumsporozoite vaccine in Thai soldiers.", "[Vaccination against malaria: initial trial with an ant-sporozoite vaccine, (NANP)3-TT (RO 40-2361) in Africa (Bobo-Dioulasso, Burkina Faso)].", "A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults." ]

[ "RTS,S/AS02A is a pre-erythrocytic malaria vaccine candidate in which a portion of the circumsporozoite surface protein (CSP) of Plasmodium falciparum is genetically linked to hepatitis B surface antigen (HBsAg) coexpressed in yeast with unfused HBsAg. The resulting particulate antigen is formulated with the adjuvant system AS02A. We have initiated the paediatric clinical development of this vaccine by conducting two sequential Phase I studies in children: a study in older children (6--11 years), followed by a second study in younger children (1--5 years). In each study, a double-blind, randomised controlled, staggered, dose-escalation design was used to evaluate 10 microg RTS,S dose (10 microg RTS,S in 0.1mL AS02A), 25 microg dose (25 microg RTS,S in 0.25mL AS02A) and finally a 50 microg dose (50 microg RTS,S in 0.5mL AS02A) of the RTS,S/AS02A candidate malaria vaccine administered according to a 0-, 1- and 3-month vaccination schedule. Safety and reactogenicity were evaluated before moving to a higher dose level. The RTS,S/AS02A vaccine was safe at all dose levels, in both age groups. No serious adverse events related to vaccination were reported. The frequency of local Grade 3 symptoms was low but tended to increase with increasing dose level. Grade 3 general adverse events in the RTS,S/AS02A groups were infrequent and of short duration. The majority of local and general Grade 3 symptoms resolved or decreased in intensity within 48h. The pattern and intensity of reactogenicity seen in these studies are similar to those of previous studies with RTS,S/AS02A. All doses were highly immunogenic for anti-CSP and anti-HBsAg antibodies. The pooled anti-CSP antibody data from the two studies showed that the 25 microg dose and 50 microg dose anti-CSP antibody response were similar at both dose levels. However, the immunogenicity of the 10 microg dose anti-CSP response was significantly lower than that of either the 50 microg or 25 microg dose. The 25 microg dose was selected for future studies of RTS,S/AS02A in paediatric populations.", "RTS,S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a new adjuvant (AS02). We did a randomised trial of the efficacy of RTS,S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia.\n 306 men aged 18-45 years were randomly assigned three doses of either RTS,S/AS02 or rabies vaccine (control). Volunteers were given sulfadoxine/pyrimethamine 2 weeks before dose 3, and kept under surveillance throughout the malaria transmission season. Blood smears were collected once a week and whenever a volunteer developed symptoms compatible with malaria. The primary endpoint was time to first infection with P. falciparum. Analysis was per protocol.\n 250 men (131 in the RTS,S/AS02 group and 119 in the control group) received three doses of vaccine and were followed up for 15 weeks. RTS,S/AS02 was safe and well tolerated. P. falciparum infections occurred significantly earlier in the control group than the RTS,S/AS02 group (Wilcoxon's test p=0.018). Vaccine efficacy, adjusted for confounders, was 34% (95% CI 8.0-53, p=0.014). Protection seemed to wane: estimated efficacy during the first 9 weeks of follow-up was 71% (46-85), but decreased to 0% (-52 to 34) in the last 6 weeks. Vaccination induced strong antibody responses to circumsporozoite protein and strong T-cell responses. Protection was not limited to the NF54 parasite genotype from which the vaccine was derived. 158 men received a fourth dose the next year and were followed up for 9 weeks; during this time, vaccine efficacy was 47% (4-71, p=0.037).\n RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection.", "It has been hypothesized that antibody induced by Plasmodium falciparum circumsporozoite protein vaccine would be effective against endemic human malaria. In a malaria endemic region of Kenya, 76 volunteers, in 38 pairs sleeping adjacently, were immunized with subunit circumsporozoite protein Asn-Ala-Asn-Pro tetrapeptide repeat-pseudomonas toxin A, or hepatitis B vaccine. After quinine and doxcycycline, volunteers were followed for illness daily, parasitemia weekly, antibody, T-lymphocyte responses, and treated if indicated. Anopheles mosquitoes resting in houses were collected, and tested for P. falciparum antigen, or dissected for sporozoites and tested for blood meal ABO type and P. falciparum antigen. Vaccine was safe, with side-effects similar in both groups, and immunogenic, engendering IgG antibody as high as 600 micrograms ml-1, but did not increase the proportion of volunteers with T-lymphocyte responses. Estimation of P. falciparum challenge averaged 0.194 potentially infective Anopheles bites/volunteer/ day. Mosquito blood meals showed no difference in biting intensity between vaccine and control groups. Both groups had similar malaria-free survival curves, cumulative positive blood slides, cumulative parasites mm-3, and numbers of parasites mm-3 on first positive blood slide, during three post-vaccination observation periods. Every volunteer had P. falciparum parastemia at least once. Vaccinees had 82% and controls 89% incidences of symptomatic parasitemia (P = 0.514, efficacy 9%, statistical power 95% probability of efficacy < 50%). Vaccine-induced anti-sporozoite antibody was not protective in this study. Within designed statistical precisions the present study is in agreement with efficacy studies in Colombia, Venezuela and Tanzania.", "After initial successful evaluation of the circumsporozoite-based vaccine RTS,S/SBAS2, developed by SmithKline Beecham Biologicals with the Walter Reed Army Institute of Research, protective efficacy of several regimens against Plasmodium falciparum challenge was determined. A controlled phase 1/2a study evaluated 1 or 2 standard doses of RTS,S/SBAS2 in 2 groups whose members received open-label therapy and 3 immunizations in blinded groups who received standard, one-half, or one-fifth doses. RTS,S/SBAS2 was safe and immunogenic in all groups. Of the 41 vaccinees and 23 control subjects who underwent sporozoite challenge, malaria developed in 7 of 10 who received 1 dose, in 7 of 14 who received 2 doses, in 3 of 6 who received 3 standard doses, in 3 of 7 who received 3 one-half doses, in 3 of 4 who received 3 one-fifth doses, and in 22 of 23 control subjects. Overall protective efficacy of RTS,S/SBAS2 was 41% (95% confidence interval, 22%-56%; P=.0006). This and previous studies have shown that 2 or 3 doses of RTS,S/SBAS2 protect against challenge with P. falciparum sporozoites.", "RTS,S/AS02A is a pre-erythrocytic stage malaria vaccine that provides partial protection against infection in malaria-naive adult volunteers and hyperimmune adults. A previous report showed that this vaccine reduced risk of clinical malaria, delayed time to new infection, and reduced episodes of severe malaria over 6 months in African children. An important remaining issue is the durability of protection against clinical disease in these children.\n We did a randomised, controlled, phase IIb trial of RTS,S/AS02A given at 0, 1, and 2 months in 2022 Mozambican children aged 1-4 years. We previously determined vaccine efficacy (VE) against clinical malaria in a double-blind phase that included study months 2.5-8.5 (VE(2.5-8.5)). We now report VE in a single-blind phase up to month 21 (VE(8.5-21)). The primary endpoint was time to first or only clinical episode of Plasmodium falciparum malaria (axillary temperature 37.5 degrees C and P falciparum asexual parasitaemia >2500 per microL) detected through a passive case detection system. We also determined VE for other case definitions and for episodes of severe malaria. This study is registered with the ClinicalTrials.gov identifier NCT00197041.\n During the single-blind phase, VE(8.5-21) was 28.9% (95% CI 8.4-44.8; p=0.008). At month 21, prevalence of P falciparum infection was 29% lower in the RTS,S/AS02A group than in the control (p=0.017). Considering the entire study period, VE(2.5-21) was 35.3% (95% CI 21.6-46.6; p<0.0001) and VE(2.5-21) for severe malaria was 48.6% (95% CI 12.3-71.0; p=0.02).\n These results show that RTS,S/AS02A confers partial protection in African children aged 1-4 years living in rural endemic areas against a range of clinical disease caused by P falciparum for at least 18 months, and confirm the potential of malaria vaccines to become credible control tools for public-health use.", "Thai soldiers were vaccinated with a recombinant protein derived from the central repeat region of the circumsporozoite (CS) protein of Plasmodium falciparum conjugated to Toxin A (detoxified) of Pseudomonas aeruginosa (R32Tox-A) to evaluate its safety, immunogenicity and efficacy. In a randomized, double-blind manner, 199 volunteers received either R32Tox-A or a control vaccine at 0, 8 and 16 weeks. Immunization was performed in a malaria non-transmission area, after completion of which volunteers were deployed to an endemic border area and monitored closely to allow early detection and treatment of infection. The vaccine was found to be safe and to elicit antibody responses in all vaccinees. Peak CS antibody (IgG) concentrations in malaria-experienced vaccinees exceeded those in malaria-naive vaccinees (mean 40.6 versus 16.1 micrograms ml-1; p = 0.005) as well as those induced by previous CS protein-derived vaccines and observed in association with natural infections. A log-rank comparison of time to falciparum malaria revealed no differences between vaccinated and non-vaccinated subjects. Secondary analyses revealed that CS antibody levels were lower in vaccinee malaria cases than in non-cases, 3 and 5 months after the third dose of vaccine (p = 0.06 and p = 0.014, respectively). Because antibody levels had fallen substantially before peak malaria transmission occurred, the question of whether high levels of CS antibody are protective remains to be resolved.", "The vaccine (NANP)3-TT is a synthetic peptide of the circumsporozoite protein (CS) of Plasmodium falciparum coupled to tetanus toxoid (TT) as protein carrier and adsorbed to aluminium hydroxide as adjuvant. The objectives of the study were to assess the immunogenicity and the protective efficacy of the vaccine in an area where malaria is endemic. The study was conducted in a zone of irrigated rice cultivation known as the Vallée du Kou to the North of Bobo-Dioulasso. Malaria transmission is permanent in the Vallée with maxima in July and November. The study was conducted from June to December 1988. It was a controlled randomised, double blind, prospective vaccine trial. A total of 123 infants from 3 to 5 months of age were randomly assigned to three groups. Group I (controls) received three doses of TT alone, group II received two doses of TT and one of (NANP)3-TT and group III received three doses of (NANP)3-TT. These vaccines were administered simultaneously with the Enlarged Program of Immunisation (EPI) vaccines. The clinical parasitological and immunological status of the children was then monitored over a period of five months. No systemic reactions to the vaccine were observed in the infants either immediately after administration or during the follow-up. Minor local tumefactions were observed in only 3% of the children. The vaccine was found to be immunogenic with a peak IgG response at day 75, when 56% (group II) and 60% (group III) showed antibody titres of at least four times that seen at day 0. The response, however, was a short duration; by day 150 the average antibody titres were not significantly different between the three groups. The incidence and the level of parasiaemia and the incidence of clinical malaria were also not significantly different for each of the three groups during the period of the study. The association of (NANP)3 with tetanus toxoid was not shown to be immunologically inhibitive. The results, despite not showing a protective effect for the vaccine (NANP)3-TT, have shown its immunogenicity and therefore suggest that further development of this vaccine may be worthwhile.", "Many malaria vaccines are currently in development, although very few have been evaluated for efficacy in the field. Plasmodium falciparum multiple epitope (ME)- thrombospondin-related adhesion protein (TRAP) candidate vaccines are designed to potently induce effector T cells and so are a departure from earlier malaria vaccines evaluated in the field in terms of their mechanism of action. ME-TRAP vaccines encode a polyepitope string and the TRAP sporozoite antigen. Two vaccine vectors encoding ME-TRAP, plasmid DNA and modified vaccinia virus Ankara (MVA), when used sequentially in a prime-boost immunisation regime, induce high frequencies of effector T cells and partial protection, manifest as delay in time to parasitaemia, in a clinical challenge model.\n A total of 372 Gambian men aged 15-45 y were randomised to receive either DNA ME-TRAP followed by MVA ME-TRAP or rabies vaccine (control). Of these men, 296 received three doses of vaccine timed to coincide with the beginning of the transmission season (141 in the DNA/MVA group and 155 in the rabies group) and were followed up. Volunteers were given sulphadoxine/pyrimethamine 2 wk before the final vaccination. Blood smears were collected weekly for 11 wk and whenever a volunteer developed symptoms compatible with malaria during the transmission season. The primary endpoint was time to first infection with asexual P. falciparum. Analysis was per protocol. DNA ME-TRAP and MVA ME-TRAP were safe and well-tolerated. Effector T cell responses to a non-vaccine strain of TRAP were 50-fold higher postvaccination in the malaria vaccine group than in the rabies vaccine group. Vaccine efficacy, adjusted for confounding factors, was 10.3% (95% confidence interval, -22% to +34%; p = 0.49). Incidence of malaria infection decreased with increasing age and was associated with ethnicity.\n DNA/MVA heterologous prime-boost vaccination is safe and highly immunogenic for effector T cell induction in a malaria-endemic area. But despite having produced a substantial reduction in liver-stage parasites in challenge studies of non-immune volunteers, this first generation T cell-inducing vaccine was ineffective at reducing the natural infection rate in semi-immune African adults." ]

[ "15895314", "8669418", "15472185", "12510818", "12198018", "9205634", "12733728", "9202789", "12663301", "8340983", "15640477", "15531696", "15755866" ]

[ "Cumulative effects of calcium supplementation and physical activity on bone accretion in premenarchal children: a double-blind randomised placebo-controlled trial.", "A follow-up study on the effects of calcium-supplement withdrawal and puberty on bone acquisition of children.", "The effect of calcium supplementation on bone density in premenarcheal females: a co-twin approach.", "Regional specificity of exercise and calcium during skeletal growth in girls: a randomized controlled trial.", "Bone mineral contents and plasma osteocalcin concentrations of Gambian children 12 and 24 mo after the withdrawal of a calcium supplement.", "A co-twin study of the effect of calcium supplementation on bone density during adolescence.", "Randomized trial of physical activity and calcium supplementation on bone mineral content in 3- to 5-year-old children.", "Bone mineral acquisition in low calcium intake children following the withdrawal of calcium supplement.", "Effect of a calcium and exercise intervention on the bone mineral status of 16-18-y-old adolescent girls.", "Calcium supplementation and bone mineral density in adolescent girls.", "Sustained effect of short-term calcium supplementation on bone mass in adolescent girls with low calcium intake.", "Effect of habitual dietary calcium intake on calcium supplementation in 12-14-y-old girls.", "Skeletal site selectivity in the effects of calcium supplementation on areal bone mineral density gain: a randomized, double-blind, placebo-controlled trial in prepubertal boys." ]

[ "High calcium intake combined with physical activity during childhood have been shown to improve bone mass accrual and bone mineral density. Our aim was to study the combined effect of calcium and exercise on bone gain in children. Two milk-powder products containing either 800 mg of calcium phosphate (calcium) or not (placebo) were randomly allocated to 113 healthy premenarchal girls on a daily basis for 1 year. The group was composed of 63 exercise (7.2 +/- 4 hours of exercise/week) and 50 sedentary (1.2 +/- 0.8 hours of exercise/week) children. The final experiment had 4 groups: exercise/calcium (n = 12), exercise/placebo (n = 42), sedentary/calcium (n = 10), and sedentary/placebo (n = 21). Bone mineral density (BMD) at 6 skeletal sites and body composition were determined by DXA. Bone age was calculated and the daily spontaneous calcium intake was assessed by a frequency questionnaire. All the tests were performed at baseline and 1 year by the same observer. BMD gains were significantly greater in the exercise/calcium group than in other groups at the total body (increase of 6.3 %, p < 0.05), lumbar spine (11 %, p < 0.05), femoral neck (8.2 %, p < 0.02), and Ward's triangle (9.3 %, p < 0.01). There was no difference between the other groups. These data suggest that calcium supplementation increases the effect of physical exercise on bone mineral acquisition in the period preceding puberty, and that calcium supplementation without physical activity does not improve the BMD acquisition during this period. Physical exercise that stimulates bone accretion needs a high calcium intake to be completely effective.", "Recent calcium supplementation trials in children have confirmed a positive but moderate effect of calcium intake on bone mineral accretion. However, the lasting effect of a higher bone mineral mass after calcium-supplement withdrawal is not known. This is an 18-mo follow-up study conducted after an 18-mo controlled calcium supplementation trial to study the persistent effect of higher bone mineral mass in children. Radial bone mineral mass was determined by single-photon absorptiometry; lumbar spine and femoral neck bone mineral mass were evaluated by dual-energy X-ray absorptiometry in 84 healthy Hong Kong children at age 8.5 y and these evaluations were repeated at age 10 y. Pubertal status was determined by Tanner staging. At the end of the follow-up, the differences in percentage gains in lumbar spine bone mineral content (12.1 +/- 8.2% compared with 14.9 +/- 10.05%, P = 0.24) and lumbar spine area (8.6 +/- 5.1% compared with 9.4 +/- 5.5%, P = 0.47) between the study and control groups disappeared. Dietary calcium intakes during follow-up were similar for the two groups (555 and 640 mg/d, P = 0.23). In multiple-regression analyses, pubertal status was the strongest correlate of bone acquisition and linear growth in the study period. In conclusion, higher percentage gains in bone mineral mass in childhood by calcium supplementation for 18 mo were reversible. Our study showed that the benefits of calcium supplementation disappear after treatment is withdrawn. Longer-term calcium trials are necessary to determine whether peak bone mass can be modified through sustained supplementation so that appropriate calcium intakes can be determined.", "The age and developmental stage at which calcium supplementation produces the greatest bone effects remain controversial. We tested the hypothesis that calcium supplementation may improve bone accrual in premenarcheal females. Fifty-one pairs of premenarcheal female twins (27 monozygotic and 24 dizygotic; mean +/- sd age, 10.3 +/- 1.5 yr) participated in a randomized, single-blind, placebo-controlled trial with one twin of each pair receiving a 1200-mg calcium carbonate (Caltrate) supplement. Areal bone mineral density (aBMD) was measured at baseline and 6, 12, 18 and 24 months. There were no within-pair differences in height, weight, or calcium intake at baseline. Calcium supplementation was associated (P < 0.05) with increased aBMD compared with placebo, adjusted for age, height, and weight at the following time points from baseline: total hip, 6 months (1.9%), 12 months (1.6%), and 18 months (2.4%); lumbar spine, 12 months (1.0%); femoral neck, 6 months (1.9%). Adjusted total body bone mineral content was higher in the calcium group at 6 months (2.0%), 12 months (2.5%), 18 months (4.6%), and 24 months (3.7%), respectively (all P < 0.001). Calcium supplementation was effective in increasing aBMD at regional sites over the first 12-18 months, but these gains were not maintained to 24 months.", "Combining exercise with calcium supplementation may produce additive or multiplicative effects at loaded sites; thus, we conducted a single blind, prospective, randomized controlled study in pre- and early-pubertal girls to test the following hypotheses. (1) At the loaded sites, exercise and calcium will produce greater benefits than exercise or calcium alone. (2) At non-loaded sites, exercise will have no benefit, whereas calcium with or without exercise will increase bone mass over that in exercise alone or no intervention. Sixty-six girls aged 8.8 +/- 0.1 years were randomly assigned to one of four study groups: moderate-impact exercise with or without calcium or low-impact exercise with or without calcium. All participants exercised for 20 minutes, three times a week and received Ca-fortified (434 +/- 19 mg/day) or non-fortified foods for 8.5 months. Analysis of covariance (ANCOVA) was used to determine interaction and main effects for exercise and calcium on bone mass after adjusting for baseline bone mineral content and growth in limb lengths. An exercise-calcium interaction was detected at the femur (7.1%, p < 0.05). In contrast, there was no exercise-calcium interaction detected at the tibia-fibula; however, there was a main effect of exercise: bone mineral content increased 3% more in the exercise than non-exercise groups (p < 0.05). Bone mineral content increased 2-4% more in the calcium-supplemented groups than the non-supplemented groups at the humerus (12.0% vs. 9.8%, respectively, p < 0.09) and radius-ulna (12.6% vs. 8.6%, respectively, p < 0.01). In conclusion, greater gains in bone mass at loaded sites may be achieved when short bouts of moderate exercise are combined with increased dietary calcium, the former conferring region-specific effects and the latter producing generalized effects.", "Our randomized, placebo-controlled supplementation study of 160 rural Gambian children aged 8.3-11.9 y showed that an increase in calcium intake of 714 mg/d for 12 mo resulted in a 5% increase in forearm bone mineral acquisition and a 22% decrease in plasma osteocalcin concentration, a bone formation marker, but had no effect on height or bone dimensions.\n We investigated whether these results were sustained after supplement withdrawal.\n All participants were followed up 12 (FU1) and 24 (FU2) mo after supplementation ended. Bone mineral content (BMC), bone mineral density (BMD), and BMC adjusted for bone width, body weight, and height (size-adjusted BMC) were measured at the midshaft and distal radius. Plasma osteocalcin concentration was measured at FU1.\n At follow-up, the calcium group had greater bone mineral status than did the placebo group at the midshaft radius (mean difference +/- SE), FU1: BMC (4.7 +/- 1.6%; P = 0.004), BMD (5.1 +/- 1.1%; P </= 0.0001), size-adjusted BMC (5.0 +/- 1.1%; P </= 0.0001); FU2: BMC (3.8 +/- 1.6%; P = 0.02), BMD (2.7 +/- 1.3%; P = 0.04), size-adjusted BMC (2.5 +/- 1.3%; P = 0.06). Similar differentials were observed at the distal radius but were not significant. No significant differences in plasma osteocalcin concentrations (FU1: -0.5 +/- 6.5%; P = 0.9) were observed between groups.\n Although some of the effects of calcium supplementation were still evident at follow-up, further studies are required to determine whether short-term increases in calcium intake have lasting benefits for Gambian children.", "The effect of calcium supplementation on bone mineral density (BMD) was evaluated in female twin pairs aged 10-17 years with a mean age of 14 years. Forty-two twin pairs (22 monozygotic, 20 dizygotic; (including one monozygotic pair from a set of triplets) completed at least 6 months of the intervention: 37 pairs to 12 months and 28 pairs to 18 months. BMD was measured by dual-energy X-ray absorptiometry (DXA). In a double-blind manner, one twin in each pair was randomly assigned to receive daily a 1000 mg effervescent calcium tablet (Sandocal 1000), and the other a placebo tablet similar in taste and appearance to the calcium supplement but containing no calcium. Compliance (at least 80% tablets consumed), as measured by tablet count, was 85% in the placebo group and 83% in the calcium group over the 18 months of the study, on average increasing dietary calcium to over 1600 mg/day. There was no within-pair difference in the change in height or weight. When the effect of calcium supplementation on BMD was compared with placebo at approximately 6, 12 and 18 months, it was found that there was a 0.015 +/- 0.007 g/ cm2 greater increase in BMD (1.62 +/- 0.84%) at the spine in those on calcium after 18 months. At the end of the first 6 months there was a significant within-pair difference of 1.53 +/- 0.56% at the spine and 1.27 +/- 0.50% at the hip. However, there were no significant differences in the changes in BMD after the initial effect over the first 6 months. Therefore, we found an increase in BMD at the spine with calcium supplementation in females with a mean age of 14 years. The greatest effect was seen in the first 6 months; thereafter the difference was maintained, but there was no accelerated increase in BMD associated with calcium supplementation. The continuance of the intervention until the attainment of peak bone mass and follow-up after cessation of calcium supplementation will be important in clarifying the optimal timing for increased dietary calcium and the sustained, long-term effects of this intervention.", "A meta-analysis of adult exercise studies and an infant activity trial show a possible interaction between physical activity and calcium intake on bone. This randomized trial of activity and calcium supplementation was conducted in 239 children aged 3-5 years (178 completed). Children were randomized to participate in either gross motor or fine motor activities for 30 minutes/day, 5 days per week for 12 months. Within each group, children received either calcium (1000 mg/day) or placebo. Total body and regional bone mineral content by DXA and 20% distal tibia measurements by peripheral quantitative computed tomography (pQCT) were obtained at 0 and 12 months. Three-day diet records and 48-h accelerometer readings were obtained at 0, 6, and 12 months. Higher activity levels were observed in gross motor versus fine motor activity groups, and calcium intake was greater in calcium versus placebo (1354 +/- 301 vs. 940 +/- 258 mg/day, p < 0.001). Main effects of activity and calcium group were not significant for total body bone mineral content or leg bone mineral content by DXA. However, the difference in leg bone mineral content gain between gross motor and fine motor was more pronounced in children receiving calcium versus placebo (interaction, p = 0.05). Children in the gross motor group had greater tibia periosteal and endosteal circumferences by pQCT compared with children in the fine motor group at study completion (p < 0.05). There was a significant interaction (both p < or = 0.02) between supplement and activity groups in both cortical thickness and cortical area: among children receiving placebo, thickness and area were smaller with gross motor activity compared with fine motor activity, but among children receiving calcium, thickness and area were larger with gross motor activity. These findings indicate that calcium intake modifies the bone response to activity in young children.", "Our recent 18-month calcium supplementation trial demonstrated a significant increase in radial bone mineral mass in 7-year-old children with calcium intake approximately 300 mg/day (Am J Clin Nutr 1994; 60: 744-50). The persistence of higher bone mass after cessation of calcium supplementation is unknown. This is a follow-up study to investigate the lasting effect of calcium supplementation on bone acquisition. Subjects were 159 Chinese children aged 8.7 years. Distal one-third radial bone mineral content (BMC) and bone width (BW) were measured by single-photon absorptiometry. After 12 months, the significant difference in mean +/- SD percentage radial BMC disappeared between the study and control groups (7.34 +/- 6.77% vs 8.67 +/- 6.46%, p > 0.05). Dietary calcium intakes were similar between the groups. During the supplementation phase, the study group had 17.9% greater BMC gain than that of controls. In the follow-up phase, however, the study group had 16.1% less BMC gain than that of controls. It appears that an increased acquisition rate during the supplementation phase was almost balanced by a reduced acquisition rate during follow-up phase. Moreover, throughout the entire 30-month period, the overall BMC acquisition rates of the study and control groups were 25% and 23.8%, respectively. Hence, the overall acquisition rate of the study group was only 5% higher than that of controls. Therefore, the effect of calcium supplementation on bone mineral gain appears to reflect a transient reduction in bone turnover rate. Longer-term calcium trials are necessary to confirm whether a sustainable higher calcium intake throughout childhood will enhance peak bone mass.", "Osteoporosis may be prevented or delayed by maximizing peak bone mass through diet modification and physical activity during adolescence.\n We studied whether increases in calcium intake and physical activity effectively increase the bone mineral status of adolescent girls aged 16-18 y.\n We conducted a 15.5-mo study of calcium supplementation (1000 mg Ca/d as carbonate) in 144 adolescent girls aged 17.3 +/- 0.3 y ( +/- SD). The subjects were randomly allocated to an exercise (three 45-min exercise-to-music classes/wk during term time) or nonexercise group. Dual-energy X-ray absorptiometry of the whole body, spine, forearm, and hip was performed before and after intervention.\n The mean (+/- SD) percentage of subjects compliant with supplement taking was 70 +/- 27% and with exercise class attendance was 36 +/- 25%. Baseline calcium intake was 938 +/- 411 mg/d. Calcium supplementation significantly increased size-adjusted bone mineral content. The effect was stronger in subjects with good compliance (percentage difference +/- SE): whole body, 0.8 +/- 0.3% (P < or = 0.01); lumbar spine, 1.9 +/- 0.5% (P < or = 0.001); ultradistal radius, 1.3 +/- 0.6% (P < or = 0.05); total hip, 2.7 +/- 0.6% (P < or = 0.001); femoral neck, 2.2 +/- 0.7% (P < or = 0.001); trochanter, 4.8 +/- 0.9% (P < or = 0.001). Attendance at > 50% of the exercise sessions was significant at the total hip (1.4 +/- 0.7%; P < or = 0.05) and trochanter (2.6 +/- 1.2%; P < or = 0.05).\n Calcium supplementation and exercise enhanced bone mineral status in adolescent girls. Whether this is a lasting benefit, leading to the optimization of peak bone mass and a reduction in fracture risk, needs to be determined.", "To evaluate the effect of calcium supplementation on bone acquisition in adolescent white girls.\n A randomized, double-blind, placebo-controlled trial of the effect of 18 months of calcium supplementation on bone density and bone mass.\n Ninety-four girls with a mean age of 11.9 + 0.5 years at study entry.\n University hospital in a small town.\n Calcium supplementation, 500 mg/d calcium as calcium citrate malate; controls received placebo pills.\n Bone mineral density and bone mineral content of the lumbar spine and total body were measured by dual-energy x-ray absorptiometry and calcium excretion from 24-hour urine specimens.\n Calcium intake from dietary sources averaged 960 mg/d for the entire study group. The supplemented group received, on average, an additional 354 mg/d of calcium. The supplemented group compared with the placebo group had greater increases of lumbar spine bone density (18.7% vs 15.8%; P = .03), lumbar spine bone mineral content (39.4% vs 34.7%; P = .06), total body bone mineral density (9.6% vs 8.3%; P = .05), and 24-hour urinary calcium excretion (90.4 vs 72.9 mg/d; P = .02), respectively.\n Increasing daily calcium intake from 80% of the recommended daily allowance to 110% via supplementation with calcium citrate malate resulted in significant increases in total body and spinal bone density in adolescent girls. The increase of 24 g of bone gain per year among the supplemented group translates to an additional 1.3% skeletal mass per year during adolescent growth, which may provide protection against future osteoporotic fracture.", "The effect of short-term calcium supplementation on peak bone mass in adolescent girls is not completely defined. In our previous double-blind, placebo-controlled, calcium-supplementation study (1000 mg calcium carbonate/d), we showed that calcium supplementation of postmenarcheal girls with low calcium intakes enhances bone mineral acquisition.\n The objective of this follow-up study, conducted 3.5 y after the end of calcium supplementation, was to investigate the sustained effect of calcium supplementation on bone mineral mass.\n Anthropometric data, nutrient intakes, and bone variables were reassessed in 96 of the 100 adolescent girls whose data had been studied at the end of the supplementation period. Bone mineral content and bone mineral density (BMD) of the total body, lumbar spine, and femoral neck were determined by dual-energy X-ray absorptiometry.\n The calcium-supplemented group tended to have a greater accretion of total-body BMD (TBBMD) than did the control group 3.5 y after the end of supplementation. The finding was statistically significant in the active-treatment cohort (n = 17 in the calcium-supplemented group and 28 in the placebo group), who had a compliance rate of > or =75% during the intervention study. In a multivariate linear-regression analysis, TBBMD accretion from the beginning of the intervention study to the follow-up study in the active-treatment cohort was attributed to calcium supplementation and to the time since inclusion in the initial study.\n Calcium supplementation for 1 y in postmenarcheal girls with low calcium intakes may provide a sustained effect on the basis of TBBMD measurements in participants with compliance rates of > or =75%.", "There is no agreement on how much calcium young girls need for optimal bone mineralization.\n We evaluated whether the effect of calcium supplementation on whole-body bone mineral accretion depends on habitual calcium intake.\n This was a randomized, double-blind, placebo-controlled, 1-y calcium intervention study of girls aged 12-14 y selected from a larger group according to habitual calcium intake: subgroup A (n = 60) habitually consumed 1000-1307 mg/d (40th-60th percentile), and subgroup B (n = 53) habitually consumed <713 mg/d (<20th percentile). The girls from each subgroup were randomly assigned to receive either 500 mg Ca/d or placebo. Whole-body bone mineral content (BMC), bone area (BA), bone mineral density (BMD), and BMC adjusted for BA, height, and weight (size-adjusted BMC) were measured at baseline and after 1 y.\n There was no significant effect modification of baseline habitual calcium intake on the relation between calcium supplementation and height, weight, BMC, size-adjusted BMC, BA, BMD, or alkaline phosphatase. Calcium supplementation had an effect on BMD (0.8%; P = 0.049) and tended to show signs of an effect on size-adjusted BMC (0.5%; P = 0.08).\n A modest effect of calcium supplementation on BMD was shown. However, the effect was independent of habitual calcium intake.", "Calcium supplementation during childhood and adolescence is considered an early means of preventing osteoporosis in adults. Prepuberty is an opportune time for detecting the benefits of calcium in girls.\n The objective was to assess whether calcium supplementation increases bone mass gain in prepubertal boys in a skeletal site-specific manner.\n In a 12-month double-blind, placebo-controlled trial with 1-yr follow-up, 235 healthy prepubertal boys aged 7.4 +/- 0.4 yr (mean +/- sd) were randomized to receive two food products providing 850 mg/d calcium (calcium supplement group, n = 116) or an isocaloric placebo (n = 119). Areal bone mineral density (aBMD) was determined by dual-energy x-ray absorptiometry at radius (two sites), hip (two sites), femoral diaphysis (FDia), and L2-L4 vertebrae.\n At 12 months, aBMD gain was greater at the FDia and at the mean of the five appendicular skeletal sites in the calcium supplement group in both intention-to-treat analysis [76 +/- 32 vs. 64 +/- 33 mg/cm(2).yr; difference, 12.0 (95% confidence interval, CI, 3.6-20.3), P = 0.006; and 33 +/- 16 vs. 28 +/- 16 mg/cm(2).yr; difference, 5.1 (95% CI, 0.9-9.2); P = 0.018, respectively] and active treatment analysis [81 +/- 32 vs. 64 +/- 31 mg/cm(2).yr; difference, 17.2 (95% CI, 7.9-26.5); n = 174, P < 0.001; and 35 +/- 16 vs. 28 +/- 14 mg/cm(2).yr; difference, 7.5 (95% CI, 2.9-12.2); P = 0.002]. There was no beneficial effect of calcium on lumbar spine. The calcium effect was still detectable by ANOVA repeated measures analysis at the FDia (P = 0.004) and at the mean of the five appendicular skeletal sites (P = 0.002) 1 yr after the end of intervention (active treatment analysis). There was no change in bone size.\n In prepubertal boys, calcium-enriched foods increased aBMD at several appendicular skeleton sites, but not at the lumbar spine, and this without any bone size change. This effect was maintained 1 yr after treatment discontinuation." ]

[ "2669554", "9230238", "9894371", "2090474", "3556202", "9655717", "9627589", "6721271", "3287996", "9525445", "3276257", "9596304", "9864004", "9768574", "2035313", "1579391", "1878641", "3512282", "9358137" ]

[ "Comparison of dose-response effects of inhaled beclomethasone dipropionate and budesonide in the management of asthma.", "Short-term knemometry and urine cortisol excretion in children treated with fluticasone propionate and budesonide: a dose response study.", "Initial loading (400 micrograms twice daily) versus static (400 micrograms nocte) dose budesonide for asthma management. PLAN Research Group.", "Long-term effects of budesonide on airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthmatics.", "Effect of inhaled budesonide on severe steroid-dependent asthma.", "Starting with a higher dose of inhaled corticosteroids in primary care asthma treatment.", "Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma.", "Use of spacers to facilitate inhaled corticosteroid treatment of asthma.", "A double-blind dose-response study of budesonide by inhalation in patients with bronchial asthma.", "Effects of budesonide by means of the Turbuhaler on the hypothalmic-pituitary-adrenal axis in asthmatic subjects: a dose-response study.", "Dosage and time effects of inhaled budesonide on bronchial hyperreactivity.", "Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group.", "Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids.", "Comparison of 3 different doses of budesonide and placebo on the early asthmatic response to inhaled allergen.", "Adrenal function in asthmatic children treated with inhaled budesonide.", "Controlled study of linear growth in asthmatic children during treatment with inhaled glucocorticosteroids.", "Growth of asthmatic children during treatment with budesonide: a double blind trial.", "High-dose inhaled budesonide in treatment of severe steroid-dependent asthma.", "Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group." ]

[ "The dose-response effects of inhaled beclomethasone dipropionate (BDP) and budesonide (BUD) administered b.i.d. with the aid of metered dose aerosols were studied in 128 patients (67 men and 61 women, mean age 53 years) suffering from asthma bronchiale. The study was designed as a multi-centre, double-blind, four-period cross-over study, followed by a single-blind double placebo period. BDP was administered in doses of 400 and 1000 micrograms, and BUD in doses of 400 and 800 micrograms. The results in terms of peak expiratory flow (PEF) in the morning and evening, daily symptoms score and use of inhaled beta 2-agonists did not reveal any clinically significant differences between the drugs or between high (800 micrograms BUD, 1000 micrograms BDP) and low (400 micrograms BUD/BDP) doses. However, statistically significant differences were recorded for the corresponding parameters when comparing the placebo with preceding steroid periods. Adverse effects consisting mainly of oropharyngeal candidiasis, hoarseness and cough occurred in 54 of 468 treatment months (12%). The carry-over effects of inhaled steroids are longer lasting than was previously assumed.", "Few thorough comparisons of the systemic effects of inhaled corticosteroids in children are available. The aim of this study was to compare the effect of budesonide and fluticasone propionate on short-term lower leg growth. Fluticasone propionate, budesonide and placebo were administered for 2 weeks in a randomized, double-blind, double-dummy, cross-over design. Twenty four children aged 6-12 yrs received 200 microg x day(-1) of each drug, or placebo. Another 24 children aged 6-12 years received 400 microg x day(-1) of each drug, or placebo. Dry powder inhalers were used. Lower leg length was measured by knemometry twice a week during all three treatment periods, and 24 h cortisol excretion in the urine was measured at the end of each period. In the low-dose group, lower leg growth rate was the same during treatment with placebo (0.35 mm x week(-1)), fluticasone propionate (0.38 mm x week(-1)) or budesonide (0.26 mm x week(-1)). No significant difference (p=0.39) in lower leg growth rate was found between treatment with 400 microg x day(-1) budesonide (0.30 mm x week(-1)) and 400 microg fluticasone propionate treatment (0.37 mm x week(-1)). Growth rate during treatment with budesonide, 400 microg x day(-1), was significantly lower than during placebo treatment (0.52 mm x week(-1)). Cortisol excretion in the urine during treatment with 200 microg x day(-1) fluticasone propionate was significantly reduced as compared with placebo (p=0.006), but not when compared with 200 microg x day(-1) budesonide (p=0.07). Budesonide 200 microg x day(-1) was not significantly different from placebo. Fluticasone propionate and budesonide, both at 400 microg x day(-1), resulted in a significant reduction in cortisol excretion in the urine as compared with placebo (p=0.001). It is concluded that, dose-for-dose, budesonide Turbuhaler and fluticasone propionate Diskhaler have similar systemic effects.", "This double-blind study aimed to determine whether superior asthma control is achieved with budesonide (Pulmicort Turbohaler) at a loading dose (LD) (400 micrograms b.d.) for 6 weeks, followed by step down to 400 micrograms nocte for 12 weeks, compared with a static dose (SD) (400 micrograms nocte) for 18 weeks. A total of 682 patients (mean peak expiratory flow rate (PEFR) 413 l/min), who demonstrated > or = 15% reversibility in PEFR, were randomised into the study. After 18 weeks, patients experienced improvements in morning PEFR (+45 l/min, both groups), symptom score (LD -0.57, SD -0.49, on a scale of 0-3), sleep disturbance (LD -1.21 nights/week, SD -1.06 nights/week) and beta 2-agonist use (LD -1.36 puffs/day, SD -1.06 puffs/day), within both groups (each p = 0.0001). At 18 weeks, 82% (LD) and 84% (SD) of patients benefited from no nocturnal wakening in the previous 7 days. Overall, at 18 weeks, asthma control was not significantly different between the groups. After 6 weeks, improvements in morning PEFR (LD +36 l/min, SD +26 l/min) and beta 2-agonist use (LD -1.10 puffs/day, SD -0.94 puffs/day) were greater in the loading dose than in the static dose group (each p < 0.05). The greater improvement in morning PEFR in the loading dose group was significant by day 7 (p < 0.05). While both regimens are equally effective in achieving asthma control at 18 weeks, early clinical advantage is gained with initial loading dose budesonide (400 micrograms b.d.).", "Budesonide 400 micrograms daily, in nonsteroid-dependent asthma, can produce improvements in airway responsiveness and clinical asthma severity, with some patients returning to normal responsiveness and becoming asymptomatic. This study examined whether similar improvements occur when asthmatics, who are dependent upon inhaled steroids, take either a regular maintenance dose of inhaled steroid or twice that amount for a year. Thirty two asthmatics were each stabilized on the minimum amount of inhaled steroid that would keep symptoms non-troublesome. In a double-blind, randomized manner, half were assigned to remain on a maintenance dose (MD) and the rest received twice that dose (MDx2) for one year. Before and monthly throughout the study, airway responsiveness to methacholine was measured and clinical asthma severity assessed by questionnaire, inhaled bronchodilator use and number of asthma exacerbations. There was a significant improvement in airway responsiveness and clinical asthma severity in both treatment groups. Those on MDx2 showed the greatest improvement but the difference between the two groups did not reach significance. This study provides strong evidence that prolonged use of inhaled steroids is associated with improvement in airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthma with a suggestion that the improvements are dose related.", "Twenty-four patients with severe steroid-dependent asthma participated in a double-blind cross-over study performed in two centers. After a run-in period of 2 weeks when beclomethasone dipropionate (BDP) (400 micrograms/day) was used, the patients were treated for 4 weeks with either a high-dose (1600 micrograms/day) or a low-dose (400 micrograms/day) of budesonide (Pulmicort). Thereafter the doses of budesonide were switched and the treatment continued for a further 4-week period. Patients treated with high-dose budesonide displayed significant improvements in airway functions. In addition, subjective scores for cough, sputum production and dyspnoea were more improved in the high-dose group than in the low-dose group. The need for concomitant beta 2-agonist therapy was also significantly reduced during the high-dose treatment. No significant changes in plasma cortisol levels were detected and no adverse effects of importance were registered. The results indicate that high-dose budesonide treatment improves the clinical status of patients with severe steroid-dependent asthma more than a low-dose therapy but without causing systemic side-effects.", "New British guidelines on the treatment of asthma (9) advocate starting with a higher dose of inhaled corticosteroids in newly detected asthma patients. We investigated whether initiating inhaled steroid treatment with a higher dose is clinically more effective than a lower dose in steroid naive patients with asthma. The study had a 13-wk randomized, double-blind, parallel design: 1-mo treatment with 400 microg budesonide twice a day, or 100 microg budesonide twice a day by dry powder inhaler, and follow-up treatment period of 2 mo with 200 microg budesonide once daily for all patients. Forty patients started with 400 microg budesonide twice daily, 44 with 100 microg budesonide twice daily. Mean age was 32 yr, baseline FEV1 value 84% predicted, reversibility 9% from baseline, and mean bronchodilator use 1.6 inhalations/d in the run-in period. After 4 wk of treatment with 400 microg and 100 microg budesonide twice daily mean morning peak expiratory flow (PEF) increased 27 L/min (SD 50), and 38 L/ min (SD 53), respectively (p = 0.30); mean symptom score improved from 1.1 to 0.6 and from 1.1 to 0.5. These effects were maintained in the 2 mo follow-up. This study suggests that starting inhaled corticosteroids at a higher dose is not superior to a lower dose in the treatment of newly detected asthma.", "To determine the efficacy and safety of budesonide delivered by an inhalation-driven dry powder inhaler (Turbuhaler) in children with moderate to severe persistent asthma.\n In our randomized, double-blind, placebo-controlled, parallel-group, multicenter study, a total of 404 children with asthma, who were aged 6 to 18 years and who had been receiving inhaled glucocorticosteroid therapy, were randomly assigned to receive either 100, 200, or 400 micrograms of budesonide or placebo twice daily for 12 weeks. At baseline, mean forced expiratory volume in 1 second (FEV1) was 74.6% (range, 30.7% to 123.3%) of the predicted normal value.\n Patients in each of the three budesonide treatment groups showed significant dose-related improvements in lung function (morning peak expiratory flow and FEV1), in asthma symptoms, and with a significant decrease in inhaled beta 2-agonist use in comparison with placebo. Improvements were evident within 2 weeks and were maintained throughout the 12 weeks. Budesonide treatment had no significant effect on hypothalamic-pituitary-adrenal axis function, and the incidence of reported adverse events was similar in all treatment groups.\n Budesonide administered via a dry powder inhaler provided dose-related improvements in lung function and clinical status and was well tolerated by children (6 to 18 years of age) with moderate to severe persistent asthma.", "Budesonide, a topically active corticosteroid, was administered in doses of 400 and 1,600 micrograms/day to 35 asthmatic adults, using a standard inhalation device or a tube or cone spacer. The spacers reduced oropharyngeal candidiasis by an amount equivalent to a 90% reduction in drug dose (p = less than 0.005) and doubled the drug's overall antiasthmatic potency (delta FEV1, p = 0.05) without significantly increasing its overall effect on blood eosinophils (p = 0.14) or the A.M. serum cortisol (p = 0.12). Steroid-induced neutrophilia increased by an amount approximating that produced by an extra half tablet of prednisone per day (p = 0.002). Both the airways and systemic effects of the spacers were greater in patients who had small airways dysfunction present prior to the study. The data suggest an increase in intrapulmonary drug deposition during spacer treatment without a material shift in regional delivery within the lung. Spacers should be particularly useful for patients whose response to inhaled steroid is compromised by by dose-limiting oropharyngeal complications. They can also reduce drug costs. They should be used selectively in children until their effect on regional intrapulmonary drug deposition has been more clearly defined.", "Budesonide by inhalation and placebo were tested in 18 patients with moderate chronic bronchial asthma. Three dose levels of budesonide were used (25, 100 and 400 micrograms q.i.d.) and the patients were to take two puffs q.i.d. in all periods. The active treatment was investigated using double-blind cross-over technique, and placebo at the end of the trial. The duration of each treatment period was 2 weeks. The study showed a high drop-out frequency while on placebo and that the PEF values were influenced in a dose-dependent way by budesonide. In spite of the double-blindness the patients had a tendency towards overuse of the trial aerosol on the lowest dose, but they used significantly less than prescribed during the period with the highest dose. No side effects were reported.", "As a general phenomenon, corticosteroids may suppress the activity in the hypothalamic-pituitary-adrenal (HPA) axis. The adrenal stimulation test is a commonly used method to assess the relative risk of exogenous corticosteroids to induce systemic side effects.\n This clinical trial was performed to assess the effects of budesonide on the HPA axis (at 800, 1600, or 3200 microg/day, given as a twice daily regimen, administered by means of the Turbuhaler) in adult patients with mild, non-steroid-dependent asthma.\n Sixty-four asthmatic patients received budesonide or placebo by inhalation or 10 mg/day oral prednisone once daily as a positive control in a double-blind, double-dummy, randomized, placebo-controlled, parallel-group, multicenter study. Plasma cortisol concentration was measured to assess the effect on the HPA axis before and during a 6-hour infusion of synthetic adrenocorticotropic hormone (ACTH), cosyntropin.\n After 6 weeks of treatment, plasma cortisol concentrations after adrenal stimulation by cosyntropin infusion had fallen by 4% in the placebo group; by 13%, 11%, and 27% in the budesonide groups (800, 1600, and 3200 microg/day, respectively); and by 35% in the prednisone group. The decrease was significant only in the 3200 microg/day budesonide (p = 0.03) and prednisone (p = 0.005) groups. Over the same time period, decreases in basal plasma cortisol concentrations were 1% in the placebo group; 19%, 19%, and 34% in the three budesonide groups; and 37% in the prednisone group. Only in the prednisone group was the decrease significant (p = 0.03 vs placebo).\n In this study budesonide inhaled by means of the Turbuhaler, at doses recommended for clinical use (800 or 1600 microg/day), did not produce any statistically significant suppression of the HPA axis compared with placebo.", "In a double-blind study of 2 parallel groups of 15 allergic asthmatic patients each, we investigated whether treatment with inhaled budesonide has a dose- and time-dependent effect on the degree of bronchial hyperreactivity. The patients were randomly allocated to treatment with either 200 or 800 micrograms budesonide per day for a period of 8 wk. The active treatment period was preceded by a selection period of 3 wk, and a single-blind placebo period of 2 wk. During these initial 5 wk the maintenance treatment of the patients, including cromolyn sodium and inhaled corticosteroids, was withheld. Spirometry and inhalation provocation tests with methacholine were carried out, and the symptom score was recorded every 2 wk. The methacholine provocation concentrations (geometric mean) causing a decrease in FEV1 of 20% (PC20) in the 200 and 800 micrograms/day treatment groups just before the active treatment period were 0.90 and 0.91 mg/ml, respectively. These values increased significantly to 1.21 and 1.84 mg/ml after 2 wk of treatment (p less than 0.05 and p less than 0.001, respectively) and to 1.55 and 2.74 mg/ml after 8 wk of treatment (p less than 0.01 and p less than 0.001). During the whole study period budesonide in a dosage of 800 micrograms/day induced a significantly larger change in PC20 than in a dosage of 200 micrograms/day. The FEV1 before treatment was 91 +/- 3% (SEM) and 84 +/- 2% of the predicted value in the 200 and 800 micrograms/day treatment groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "To determine the ability of budesonide via an inhaler (Pulmicort Turbuhaler; Astra Draco AB) to replace oral glucocorticosteroids (GCSs) in adult subjects with moderate-to-severe asthma.\n Double-blind, randomized, and placebo-controlled study, with parallel groups.\n Multicenter study in outpatient setting.\n Eighty men and 79 women, aged 20 to 69 years, with moderate-to-severe asthma and a mean FEV1 of 58.3% predicted normal. All subjects were receiving oral GCS treatment and 79% of subjects were also receiving inhaled beclomethasone dipropionate (BDP). The mean daily doses of prednisone at baseline, including converted dose of BDP, for the placebo, budesonide 400 microg, and budesonide 800 microg, respectively, were 19.7 mg, 19.5 mg, and 18.7 mg.\n After a 2-week baseline period, subjects entered a 20-week treatment period, during which the oral dose of prednisone was reduced by forced down-titration at 2-weekly intervals.\n Subjects receiving 400 microg or 800 microg bid of budesonide achieved a significantly greater reduction (82.9% and 79.0% respectively) in oral GCS dose compared with placebo-treated subjects (27%; p<0.001). Two thirds of the subjects receiving budesonide were able to achieve sustained oral corticosteroid cessation, compared with 8% in the placebo group. Additionally, both doses of budesonide resulted in significant improvement in results of pulmonary function tests and asthma symptoms scores, and a significant decrease in the use of bronchodilator therapy. The mean plasma cortisol levels before and after adrenocorticotropic hormone stimulation increased most toward the normal range in the budesonide-treated groups compared with placebo-treated subjects.\n Budesonide administered via Turbuhaler has a significant oral GCS-sparing capacity with maintained or improved asthma control in adult subjects with moderate-to-severe asthma.", "The aim of the present study was to examine the efficacy of low-dose inhaled budesonide (BUD) administered via Turbuhaler once or twice daily on symptoms, lung function and bronchial hyperreactivity in children with mild asthma. One hundred and sixty-three children (mean age 9.9 yrs, 56 females/107 males) with mild asthma (forced expiratory volume in one second (FEV1) 103% of predicted, morning peak expiratory flow (PEF) 87% pred, reversibility in FEV1 3%, fall in FEV1 after exercise 10.4% from pre-exercise value) and not previously treated with inhaled steroids, were included in a double-blind, randomized, parallel-group study. After a two-week run-in period, the children received inhaled BUD 100 microg or 200 microg once daily in the morning, 100 microg twice daily or placebo for 12 weeks. Exercise and methacholine challenges were performed before and at the end of treatment. After 12 weeks of therapy, the fall in FEV1 after an exercise test was significantly less in all three BUD groups (43-5.1%) than in the placebo group (8.6%). Bronchial hyperreactivity to methacholine with the provocative dose causing a 20% fall in FEV1 decreased significantly in the BUD 100 microg twice-daily group compared with placebo (ratio at the end of treatment 156%). Changes in baseline lung function (FEV1 and PEF) were less marked than changes in bronchial responsiveness. In conclusion, low doses of inhaled budesonide, given once or twice daily, provided protection against exercise-induced bronchoconstriction in children with mild asthma and near normal lung function.", "A simple laboratory method to evaluate relative potency of inhaled corticosteroids in asthma would be valuable. Single-dose studies with the allergen-induced late asthmatic response have failed to show a useful dose-response relationship. Treatment for several days with inhaled corticosteroids will also inhibit the allergen-induced early asthmatic response.\n Twelve atopic asthmatic subjects were studied during a season when no medications were required except ipratropium bromide as needed. These subjects had positive allergen and methacholine inhalation tests and FEV1 greater than 70% of predicted value. A double-blind, randomized, cross-over study compared placebo and budesonide 100, 200, and 400 microg administered by means of Turbuhaler twice daily for 7 days with 6-day washout periods. Methacholine PC20 was measured before and after 6 days of treatment, and allergen PC15 was measured after 7 days of treatment.\n The allergen PC15 (n = 11) was significantly larger (P = .0001) for all doses of budesonide compared with placebo, but there was no significant difference between the 3 doses of budesonide, and no dose response was demonstrated. The methacholine PC20 was significantly larger after all budesonide treatments compared with placebo (P = .024), but there was no difference between the 3 doses. There was a progressive increase in the allergen PC15 chronologically (sequence effect) that was not explained by improvement in FEV1 or airway responsiveness; sequence effects were not seen for FEV1 or for pretreatment or posttreatment methacholine PC20. Statistical adjustment for sequence effect did not alter allergen PC15 statistics.\n A 7-day course of budesonide administered by means of Turbuhaler at 200, 400, or 800 microg per day provided marked and significant inhibition of the allergen-induced early asthmatic response compared with placebo. There was, however, no difference between the 3 doses. Therefore this method with these doses is not useful for providing assessment of relative potency.", "The effect of the inhaled topical steroid budesonide on adrenal function was evaluated in 33 children (aged 7-15 years) with moderate bronchial asthma. The trial was designed as a prospective single-blind study of the effect of budesonide in daily doses of 200 microgram through 400 microgram to 800 micrograms in three randomized consecutive periods of 8 weeks. The unstimulated diurnal production of cortisol was assessed by measurement of free cortisol in 24-hour urine samples at the end of each period. No significant dose-related suppression was found. The cortisol production did not differ significantly during treatment with 800 microgram budesonide as compared to treatment with 200 microgram budesonide (95% confidence interval: 74%-112%). It is concluded, that budesonide is a topical steroid with a favourable ratio between topical and systemic effects in asthmatic children.", "Linear growth was investigated with weekly knemometry in a population of 43 schoolchildren with mild asthma treated with inhaled budesonide. The design was a randomized, double-blind, parallel group study with three dose groups of 200, 400, and 800 micrograms of budesonide per day. Each dose group received budesonide for 8 consecutive weeks. Placebo was given for either 4 weeks before or after budesonide treatment. Twelve children in the 200-micrograms group, 14 in the 400-micrograms group, and 12 in the 800-micrograms group completed the 12-week study period. There was no significant difference in mean growth velocity among the three dose groups during placebo treatment. Compared with placebo (growth velocity: 0.39 mm/wk), mean lower leg growth velocity was reduced with 0.26 mm/wk (P less than .001, t = 5.0, df = 11; 95% confidence interval 0.14 to 0.37 mm/wk) in children treated with 800 micrograms of budesonide. There was no statistically significant difference in growth velocity between 200- or 400-micrograms budesonide treatments and placebo. These data indicate that inhaled budesonide can be safely used in doses up to 400 micrograms/d in schoolchildren with asthma.", "To determine whether the inhaled glucocorticosteroid budesonide has any adverse effect on short term linear growth in children with mild asthma.\n Outpatient clinic in secondary referral centre.\n 15 children aged 6-13 years with normal statural growth velocity during the previous year, no signs of puberty, and no use of systemic or topical steroids in the two months before the study. DESIGN OF INTERVENTIONS: Double blind, randomised crossover trial with two active periods in which budesonide was given in divided daily doses of 200 micrograms and 800 micrograms. During run in and two washout periods placebo was given. After the second washout period the children received open treatment with 400 micrograms budesonide daily. All periods were of 18 days' duration.\n Growth of the lower leg as measured twice a week by knemometry.\n Mean growth velocity of the lower leg was 0.63 mm/week during run in and during washout 0.64 mm/week. Budesonide treatment was associated with a significant dose related reduction of growth velocity: the mean reduction in growth velocity during treatment was 0.11 (95% confidence interval -0.15 0.36 (0.13 to 0.59) mm/week with 800 micrograms budesonide (p less than 0.05; Page's test). During treatment with 400 micrograms budesonide a reduction of 0.17 (-0.10 to 0.45) mm/week was found.\n Treatment with inhaled budesonide is associated with a dose related suppression of short term linear growth in children with mild asthma.", "Forty-five steroid-dependent asthmatic outpatients were treated twice daily for 51 weeks with a new inhalation steroid, budesonide (BUD), using a 750 ml spacer. During the initial 15 weeks the prednisone-sparing effects of a high daily dose (1600 micrograms) and a conventional dose (400 micrograms per day) were compared in a double-blind randomized trial including 50 patients. During the remaining 36 weeks 45 patients were treated openly with 1600 micrograms daily. All patients used other antiasthmatic drugs which were maintained throughout the study, except for inhalations of beta-2 agonists that could be used whenever needed. All patients but 2 were able to reduce the daily dose of oral prednisone. The mean daily dose decreased from 13.9 mg to 5.3 mg. Eighteen patients (40%) were able to discontinue oral prednisone. Adrenal gland function improved considerably as prednisone intake decreased. Oropharyngeal thrush frequency showed no change. No severe side effects were observed.", "The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide.\n After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days.\n The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater.\n In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma." ]

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[ "[Doula--a new concept in obstetrics].", "A randomized control trial of continuous support in labor by a lay doula.", "Effects of social support during parturition on maternal and infant morbidity.", "Effects of psychosocial support during labour and childbirth on breastfeeding, medical interventions, and mothers' wellbeing in a Mexican public hospital: a randomised clinical trial.", "Effect of continuous support during labor on duration of labor and rate of cesarean delivery.", "Effects of continuous intrapartum professional support on childbirth outcomes.", "Effects of female relative support in labor: a randomized controlled trial.", "The impact of intrapartum analgesia on labour and delivery outcomes in nulliparous women.", "Assessment of the effect of psychosocial support during childbirth in Ibadan, south-west Nigeria: a randomised controlled trial.", "A randomized controlled trial of continuous labor support for middle-class couples: effect on cesarean delivery rates.", "A randomized trial of one-to-one nurse support of women in labor.", "Effectiveness of nurses as providers of birth labor support in North American hospitals: a randomized controlled trial.", "Effects of labor support from close female relative on labor and maternal satisfaction in a Thai setting.", "Companionship to modify the clinical birth environment: effects on progress and perceptions of labour, and breastfeeding.", "Continuous emotional support during labor in a US hospital. A randomized controlled trial.", "Support to woman by a companion of her choice during childbirth: a randomized controlled trial." ]

[ "We wanted to study the effect of extra emotional support in the form of a non-professional woman (doula) before and during delivery. About 200 primiparae were invited to participate in a prospective study which intended to assess differences in delivery outcome between women with and without a doula. Fifty-four declined to participate, 55 had a delivery with doula and 46 were controls. Lower rate of emergency caesarean sections in the doula-group was noted. The parents as well as the staff, became to regard the doula as a valuable support during delivery.", "To compare labor outcomes in women accompanied by an additional support person (doula group) with outcomes in women who did not have this additional support person (control group).\n Randomized controlled trial.\n A women's ambulatory care center at a tertiary perinatal care hospital in New Jersey.\n Six hundred nulliparous women carrying a singleton pregnancy who had a low-risk pregnancy at the time of enrollment and were able to identify a female friend or family member willing to act as their lay doula.\n The doula group was taught traditional doula supportive techniques in two 2-hour sessions.\n Length of labor, type of delivery, type and timing of analgesia/anesthesia, and Apgar scores.\n Significantly shorter length of labor in the doula group, greater cervical dilation at the time of epidural anesthesia, and higher Apgar scores at both 1 and 5 minutes. Differences did not reach statistical significance in type of analgesia/anesthesia or cesarean delivery despite a trend toward lower cesarean delivery rates in the doula group.\n Providing low-income pregnant women with the option to choose a female friend who has received lay doula training and will act as doula during labor, along with other family members, shortens the labor process.", "Because continuous social support during labour is a component of care in many societies but inconsistent in our own, the clinical effect of support during labour on maternal and neonatal morbidity were studied. Social support was provided by female companions. Four hundred and sixty five healthy primigravidous women were enrolled using a randomised design. Compared with 249 women undergoing labour alone 168 women who had supportive female companions throughout labour had significantly fewer perinatal complications (p less than 0.001), including caesarean sections (7% v 17%, p less than 0.01) and oxytocin augmentation (2% v 13%, p less than 0.001), and fewer infants admitted to neonatal intensive care (p less than 0.10). Of the women who had an uncomplicated labour and delivery requiring no interventions, those with a companion had a significantly shorter duration of labour (7.7 hours v 15.5 hours, p less than 0.001). This study suggests that constant human support may be of great benefit to women during labour.", "To evaluate the effects of psychosocial support during labour, delivery and the immediate postpartum period provided by a female companion (doula).\n The effects of the intervention were assessed by means of a randomised clinical trial. Social support by a doula was provided to women in the intervention group, while women in the control arm received routine care.\n A large social security hospital in Mexico City.\n Seven hundred and twenty-four women with a single fetus, no previous vaginal delivery, < 6 cm of cervical dilatation, and no indications for an elective caesarean section were randomly assigned to be accompanied by a doula, or to receive routine care.\n Breastfeeding practices, duration of labour, medical interventions, mother's emotional conditions, and newborn's health.\n Blinded interviewers obtained data from the clinical records, during encounters with women in the immediate postpartum period, and at their homes 40 days after birth. Relative risks and confidence intervals were estimated for all relevant outcomes.\n The frequency of exclusive breastfeeding one month after birth was significantly higher in the intervention group (RR 1.64; I-C: 1.01-2.64), as were the behaviours that promote breastfeeding. However, the programme did not achieve a significant effect on full breastfeeding. More women in the intervention group perceived a high degree of control over the delivery experience, and the duration of labour was shorter than in the control group (4.56 hours vs 5.58 hours; RR 1.07 CI (95%) = 1.52 to -0.51). There were no effects either on medical interventions, mothers' anxiety, self-esteem, perception of pain and satisfaction, or in newborns' conditions.\n Psychosocial support by doulas had a positive effect on breastfeeding and duration of labour. It had a more limited impact on medical interventions, perhaps because of the strict routine in hospital procedures, the cultural background of the women, the short duration of the intervention, and the profile of the doulas. It is important to include psychosocial support as a component of breastfeeding promotion strategies.", "To evaluate the effect of continuous support provided by midwives during labor on the duration of the different stages of labor and the rate of cesarean delivery.\n A randomized trial of 100 eligible nulliparous women who had not received education classes on childbirth. In the intervention group (n=50), continuous support during labor was provided; the control group (n=50) did not receive continuous support.\n The two groups did not differ by age, employment, educational level, gestational age, economic status, and neonatal weight. Mean duration of the active phase of labor (167.9+/-76.3 vs 247.7+/-101 min, P<0.001), second stage of labor (34.9+/-25.4 vs 55.3+/-33.7 min, P=0.003), and the number of cesarean deliveries (4 vs 12, P=0.026) were significantly lower in the intervention group compared with the control group. The rates of oxytocin use and Apgar scores of less than 7 at 5 minutes were similar between the two groups.\n Continuous support provided by midwives during labor may reduce the duration of labor and the number of cesarean deliveries; this model of support should be available to all women.\n Copyright 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.", "The purpose of this stratified randomized trial was to determine the physical and psychological effects of continuous, one-to-one professional support on childbirth outcomes. Data were gathered during prenatal and postpartum interviews with, and from the medical records of, 103 low-risk women. All subjects had attended one of two types of prenatal education programs, were accompanied by husbands or partners during labor, and had vaginal deliveries. Subjects in the experimental group were less likely to have medication for pain relief and less likely to have episiotomies. Three variables were found to predict perceived control during childbirth--expectations of control, the presence of a continuous professional caregiver, and pain medication usage. The results demonstrate the importance of the traditional nursing support role during childbirth.", "This study was a randomized controlled trial of primigravidas in Botswana to determine the effectiveness of the presence of a female relative as a labor companion on labor outcomes.\n One hundred and nine primigravidas in uncomplicated spontaneous labor were randomly distributed into a control group who labored without family members present, and an experimental group who had a female relative with them during labor.\n Significantly more mothers in the experimental group had a spontaneous vaginal delivery (91% vs 71%), less intrapartum analgesia (53% vs 73%), less oxytocin (13% vs 30%), fewer amniotomies to augment labor (30% vs 54%), fewer vacuum extractions (4% vs 16%), and fewer cesarean sections (6% vs 13%) than in the control group. These differences were all significant at p < 0.05. Epidural analgesia was not used in the hospital at the time of the study. The only analgesics used were intramuscular pethidine or hyoscine N-butylbromide (Buscopan).\n The presence in labor of a female relative was shown to be associated with fewer interventions and a higher frequency of normal delivery compared with the outcomes of those without family member support. The presence of a female relative as a labor companion is a low-cost, preventative intervention that is consistent with the traditional cultural practices in Botswana. In the light of this and previous studies, all women giving birth in a hospital should be offered the choice of a female relative as a companion to give support during labor.", "To determine if nulliparous women intending to have epidural analgesia have a similar labour profile and delivery outcome to women who intend to have their labour managed using alternative forms of pain relief.\n A prospective randomised controlled clinical trial conducted at a tertiary obstetric institution. Nulliparous women intending to deliver vaginally with a term singleton fetus were eligible for recruitment.\n 1159 women were recruited, of whom 992 were subsequently randomised to receive continuous midwifery support (CMS) or epidural analgesia (EPI) on presentation for delivery. The duration of labour was shorter in the CMS group compared with EPI (10.7 hours (inter quartile (IQ) 7.0,15.2) versus 11.4 hours (IQ 8.2,15.2), p = 0.039). The median duration of the first stage was 8.9 hours (IQ 6,12.5) versus 9.5 hours (IQ 7,12.7) (p = 0.069), and the median duration of the second stage was 1.33 hours (IQ 0.6,2.5) versus 1.48 hours (IQ 0.77,2.6) (p = 0.034). The requirement for oxytocin augmentation in spontaneous labour was 39.8% CMS versus 46.2% EPI (p = 0.129). There was no significant difference in the caesarean section rates. The need for any operative delivery was significantly lower in CMS (43.9% CMS versus 51.5% EPI, p = 0.019).\n Nulliparous women have a high usage of epidural analgesia, regardless of their prelabour intentions. In women who do not intend to use epidural analgesia, the temporal delay in insertion compared with those who use epidural analgesia as their primary analgesic modality is associated with a small but statistically significant reduction in overall labour duration and operative delivery rates.", "To assess the effect of psychosocial support on labour outcomes.\n A randomised control trial conducted at the University College Hospital Ibadan, Nigeria, from November 2006 to 30 March 2007. Women with anticipated vaginal delivery were recruited and randomised at the antenatal clinic. The experimental group had companionship in addition to routine care throughout labour until two hours after delivery, while the controls had only routine care. The primary outcome measure was caesarean section rate. Others included duration of active phase, pain score, time of breast-feeding initiation and description of labour experience. Multivariable analyses were used to adjust for potential confounders. The level of statistical significance was set at 5%.\n Of the 632 recruited, 585 were eventually studied: 293 and 292 were in experimental and control groups, respectively. Husbands constituted about two-thirds of the companions. Women in the control group were about five times more likely to deliver by caesarean section (95% confidence interval (CI) 1.98-12.05), had significantly longer duration of active phase (P < 0.001), higher pain scores (P = 0.011) and longer interval between delivery and initiation of breast-feeding (P < 0.001). However, those in experimental group had a more satisfying labour experience (odds ratio 3.3 95% CI 2.15-5.04).\n Women with companionship had better labour outcomes compared to those without. It is desirable to adopt this practice in our health-care settings as an alternative strategy to provide comparable quality services to would-be mothers in labour.", "Previous randomized controlled studies in several different settings demonstrated the positive effects of continuous labor support by an experienced woman (doula) for low-income women laboring without the support of family members. The objective of this randomized controlled trial was to examine the perinatal effects of doula support for nulliparous middle-income women accompanied by a male partner during labor and delivery.\n Nulliparous women in the third trimester of an uncomplicated pregnancy were enrolled at childbirth education classes in Cleveland, Ohio, from 1988 through 1992. Of the 686 prenatal women recruited, 420 met enrollment criteria and completed the intervention. For the 224 women randomly assigned to the experimental group, a doula arrived shortly after hospital admission and remained throughout labor and delivery. Doula support included close physical proximity, touch, and eye contact with the laboring woman, and teaching, reassurance, and encouragement of the woman and her male partner.\n The doula group had a significantly lower cesarean delivery rate than the control group (13.4% vs 25.0%, p = 0.002), and fewer women in the doula group received epidural analgesia (64.7% vs 76.0%, p = 0.008). Among women with induced labor, those supported by a doula had a lower rate of cesarean delivery than those in the control group (12.5% vs 58.8%, p = 0.007). On questionnaires the day after delivery, 100 percent of couples with doula support rated their experience with the doula positively.\n For middle-class women laboring with the support of their male partner, the continuous presence of a doula during labor significantly decreased the likelihood of cesarean delivery and reduced the need for epidural analgesia. Women and their male partners were unequivocal in their positive opinions about laboring with the support of a doula.", "Health researchers and provider groups have recommended that women in labor should receive continuous professional support. The objective of our study was to compare the risks and benefits of one-to-one nurse labor support with usual intrapartum nursing care.\n A randomized, controlled trial was conducted in a 637-bed university hospital in Montreal, Quebec, with 413 nulliparous women who were at more than 37 weeks' gestation, carrying singletons, and in labor. Women with scheduled cesarean section, scheduled induction, breech presentation, presence of paid labor support, or cervical dilatation over 4 cm were excluded. One-to-one care consisted of the presence of a nurse during labor and birth who provided emotional support, physical comfort, and instruction for relaxation and coping techniques. Usual care consisted of care for two or three laboring women with various types of supportive activities.\n A beneficial trend due to one-to-one nurse support was found with a 17 percent reduction in risk of oxytocin stimulation (relative risk of experimental vs control = 0.83; 95% confidence interval = 0.67, 1.04). No significant differences were found in overall labor durations and overall rates of total cesarean section, cesarean section for cephalopelvic disproportion, epidural analgesia, admission to the neonatal intensive care unit, instrumental vaginal delivery, and perineal trauma.\n The beneficial trend attributed to one-to-one nursing in reduction of oxytocin stimulation suggests that implementation of recommendations for continuous professional support by intrapartum nursing staff may be appropriate in North America.", "North American cesarean delivery rates have risen dramatically since the 1960s, without concomitant improvements in perinatal or maternal health. A Cochrane Review concluded that continuous caregiver support during labor has many benefits, including reduced likelihood of cesarean delivery.\n To evaluate the effectiveness of nurses as providers of labor support in North American hospitals.\n Randomized controlled trial with prognostic stratification by center and parity. Women were enrolled during a 2-year period (May 1999 to May 2001) and followed up until 6 to 8 postpartum weeks.\n Thirteen US and Canadian hospitals with annual cesarean delivery rates of at least 15%.\n A total of 6915 women who had a live singleton fetus or twins, were 34 weeks' gestation or more, and were in established labor at randomization.\n Patients were randomly assigned to receive usual care (n = 3461) or continuous labor support by a specially trained nurse (n = 3454) during labor.\n The primary outcome measure was cesarean delivery rate. Other outcomes included intrapartum events and indicators of maternal and neonatal morbidity, both immediately after birth and in the first 6 to 8 postpartum weeks.\n Data were received for all 6915 women and their infants (n = 6949). The rates of cesarean delivery were almost identical in the 2 groups (12.5% in the continuous labor support group and 12.6% in the usual care group; P =.44). There were no significant differences in other maternal or neonatal events during labor, delivery, or the hospital stay. There were no significant differences in women's perceived control during childbirth or in depression, measured at 6 to 8 postpartum weeks. All comparisons of women's likes and dislikes, and their future preference for amount of nursing support, favored the continuous labor support group.\n In hospitals characterized by high rates of routine intrapartum interventions, continuous labor support by nurses does not affect the likelihood of cesarean delivery or other medical or psychosocial outcomes of labor and birth.", "To evaluate the efficacy of a close female relative providing emotional and physical support during active labor and birth.\n Randomized, two-group controlled clinical trial.\n Regional teaching hospital in the eastern part of Thailand with 782 beds.\n Primiparous women (N = 120) whose gestational ages were ≥ 36 weeks and who had uncomplicated pregnancies.\n Participants were randomly assigned to receive usual care and support from a chosen close female relative from admission until 2 hours after birth or usual care only. Within 24 hours of birth, labor outcomes (length of labor & type of birth) and levels of maternal satisfaction were assessed.\n Those in the experimental group had a significantly shorter duration of active labor and were more satisfied with their childbirth experiences than those in the control group. Differences between groups with respect to incidence of spontaneous delivery were not found.\n A close female relative was effective in providing supportive care during labor and delivery. The integration of this nursing intervention for women and their families at public hospitals in Thailand is supported.\n © 2012 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.", "To measure the effects of supportive companionship on labour and various aspects of adaptation to parenthood, and thus by inference the adverse effects of a clinically orientated labour environment on these processes.\n Randomized controlled trial.\n A community hospital familiar to most of the participants, with a conventional, clinically-orientated labour ward.\n Nulliparous women in uncomplicated labour.\n Supportive companionship from volunteers from the community with no medical nor nursing experience, concentrating on comfort, reassurance and praise.\n Duration of labour, use of analgesia, perceptions of labour and breastfeeding success.\n Companionship had no measurable effect on the progress of labour. Diastolic blood pressure and use of analgesia were modestly but significantly reduced. The support group were more likely to report that they felt that they had coped well during labour (60 vs 24%, P less than 0.00001). Their mean labour pain scores (26.0 vs 44.2, P less than 0.00001) and state anxiety scores (28.2 vs 37.8, P less than 0.00001) were lower than those of the control group. Compared with the control group (n = 75), at 6 weeks women in the support group (n = 74) were more likely to be breastfeeding exclusively (51 vs 29%, P less than 0.01); and to be feeding at flexible intervals (81 vs 47%, P less than 0.0001).\n Labour in a clinical environment may undermine women's feelings of competence, perceptions of labour, confidence in adapting to parenthood and initiation of successful breastfeeding. These effects may be reduced by the provision of additional companionship during labour aimed to promote self-esteem.", "The continuous presence of a supportive companion (doula) during labor and delivery in two studies in Guatemala shortened labor and reduced the need for cesarean section and other interventions. In a US hospital with modern obstetric practices, 412 healthy nulliparous women in labor were randomly assigned to a supported group (n = 212) that received the continuous support of a doula or an observed group (n = 200) that was monitored by an inconspicuous observer. Two hundred four women were assigned to a control group after delivery. Continuous labor support significantly reduced the rate of cesarean section deliveries (supported group, 8%; observed group, 13%; and control group, 18%) and forceps deliveries. Epidural anesthesia for spontaneous vaginal deliveries varied across the three groups (supported group, 7.8%; observed group, 22.6%; and control group, 55.3%). Oxytocin use, duration of labor, prolonged infant hospitalization, and maternal fever followed a similar pattern. The beneficial effects of labor support underscore the need for a review of current obstetric practices.", "To evaluate the effectiveness and safety of the support given to women by a companion of their choice during labor and delivery.\n A total of 212 primiparous women were enrolled in a randomized controlled clinical trial carried out between February 2004 and March 2005. One hundred and five women were allocated to the group in which support was permitted and 107 to the group in which there was no support. Variables regarding patient satisfaction and events related to obstetrical care, neonatal results and breastfeeding were evaluated. Student's t-test or Wilcoxon's test, chi-square or Fisher's exact test, risk ratios, and their respective 95% confidence intervals were used in the statistical analysis.\n Overall, the women in the support group were more satisfied with labor (median 88.0 versus 76.0, p < 0.0001) and delivery (median 91.4 versus 77.1, p < 0.0001). During labor, patient satisfaction was associated with the presence of a companion (RR 8.06; 95%CI: 4.84 - 13.43), with care received (RR 1.11; 95%CI: 1.01 - 1.22) and with medical guidance (RR 1.14 95%CI: 1.01 - 1.28). During delivery, satisfaction was associated with having a companion (RR 5.57, 95%CI: 3.70 - 8.38), with care received (RR 1.11 95%CI: 1.01 - 1.22) and with vaginal delivery (RR 1.33 95%CI:1.02 - 1.74). The only factor that was significantly lower in the support group was the occurrence of meconium-stained amniotic fluid (RR 0.51; 95%CI: 0.28 - 0.94). There was no statistically significant difference between the two groups with respect to any of the other variables.\n The presence of a companion of the woman's choice had a positive influence on her satisfaction with the birth process and did not interfere with other events and interventions, with neonatal outcome or breastfeeding." ]

[ "12360766", "1862126" ]

[ "Two US practitioners' experience of using essential oils for wound care.", "Ketanserin promotes wound healing: clinical and preclinical results." ]

[ "Though essential oils are a proven antiseptic, little work has investigated their use on chronic wounds. This article describes the progress and problems of a small study of five patients, who were treated with lavender and chamomile essential oils.", "nan" ]

[ "11725662" ]

[ "A two-year randomized, controlled clinical evaluation of bonded amalgam restorations." ]

[ "The clinical performance of adhesively bonded dental amalgam restorations was compared with that of traditionally placed non-bonded control amalgams in a randomized prospective study.\n One-hundred thirteen Class II Dispersalloy amalgams were placed in permanent molars and premolars of 31 (21 males, 10 females) human subjects with their informed consent. By random assignment, 60 amalgam restorations were adhesively bonded using ED Primer and Panavia 21 TC (both Kuraray Co, Japan), and 53 traditional non-bonded restorations were placed. Most preparations involved replacement of defective amalgam restorations. Clinical recalls were conducted by experienced evaluators using modified USPHS criteria for occlusal and proximal anatomic form, occlusal and proximal marginal adaptation, and occlusal and proximal surface roughness.\n For the categories of anatomic form, marginal adaptation, surface quality, and temperature sensitivity, there were no significant differences between bonded and non-bonded amalgam restorations (chi-square analysis, p > 0.05). Three non-bonded restorations were lost at 4, 7, and 24 months from preparations with no deliberate retention.\n After two years' clinical service, there were no failures among the amalgam restorations adhesively bonded using ED Primer and Panavia 21 TC, but three non-bonded restorations failed due to lack of retention. For traditional preparations, adhesively bonded amalgams of the type investigated perform as well as non-bonded amalgams over two years' clinical service." ]

[ "3887870", "7032641", "3170226", "8618295", "8583618", "10096374", "10604689", "8456052", "1361435", "2441458", "3882181" ]

[ "[Clinical application of PPC for nonspecific chronic prostatitis].", "Prostatodynia--physiological characteristics and rational management with muscle relaxants.", "[Microwave hyperthermia in chronic prostatitis and prostatodynia--preliminary results].", "Transurethral microwave thermotherapy for nonbacterial prostatitis: a randomized double-blind sham controlled study using new prostatitis specific assessment questionnaires.", "Ameliorative effect of allopurinol on nonbacterial prostatitis: a parallel double-blind controlled study.", "Effects of finasteride in patients with inflammatory chronic pelvic pain syndrome: a double-blind, placebo-controlled, pilot study.", "Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial.", "Is there a role for transrectal microwave hyperthermia of the prostate in the treatment of abacterial prostatitis and prostatodynia?", "Research in 'prostatitis syndromes': the use of alfuzosin (a new alpha 1-receptor-blocking agent) in patients mainly presenting with micturition complaints of an irritative nature and confirmed urodynamic abnormalities.", "Effects of sodium pentosanpolysulphate on symptoms related to chronic non-bacterial prostatitis. A double-blind randomized study.", "Minocycline in chronic abacterial prostatitis: a double-blind prospective trial." ]

[ "The clinical effectiveness of PPC, amino acid preparation, on nonspecific chronic prostatitis was evaluated by the double-blind test method. A mixture of two pollen extracts which has been widely employed for the treatment of chronic prostatitis was used as a control. Neither antibiotics nor anti-inflammatory drug was administered during the investigation. A total of 76 cases was reported from six facilities but 14 of them were excluded or dropped out. In 32 cases in the PPC group, subjective symptoms such as discomfort after urination, discomfort in the perineal region, pollakisuria, sense of residual urine and dysuria were improved in 50.0 approximately 61.9% and 70.0 approximately 83.3% after 2- and 4-week administrations, respectively. Similar results regarding each subjective symptom were obtained in 30 cases of the control group and there was no significant difference between the two groups. In the overall clinical effectiveness concerning subjective symptoms, the effective rate including excellently, moderately and slightly effective was 81.3% with PPC and 83.3% with control drug. However when the effective rate was limited to excellently and moderately effective, PPC was slightly superior to the control drug (50.5% versus 36.7%). In regard to prostatic tenderness by the digital examination, both PPC and control drug induced relatively good improvement after 2-week administration. The degree of improvement, however, was not increased in the subsequent 2 weeks. Sclerotic change of the prostate was poorly recovered in both groups even after 4-week treatment. Swelling of the prostate was alleviated in 12.5% of the control group after 2 weeks and in 31.8% after 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)", "Patients with a clinical diagnosis of prostatodynia were evaluated by bacteriological, urodynamic and psychological means. In a prospective study 27 patients were entered on a trial of phenoxybenzamine, baclofen and placebo. A 50% symptomatic response was reported with phenoxybenzamine.", "nan", "We investigated the effectiveness and durability of transurethral microwave thermotherapy in the treatment of chronic nonbacterial prostatitis using 2 new prostatitis specific assessments in a randomized, double-blind, sham controlled trial.\n Patients with nonbacterial prostatitis were randomly assigned to receive either transurethral microwave thermotherapy or sham therapy. Patients were assessed using a symptom severity index and symptom frequency questionnaire. These 2 new prostatitis symptom assessment tools were validated by applying them to 30 similar patients without prostatitis. All nonresponders received transurethral microwave thermotherapy at 3 months and were reassessed at 6 months. Long-term followup of the responder group averaged 21 months.\n The symptom severity index and symptom frequency questionnaire were confirmed to be valid for symptom assessment in prostatitis patients. The transurethral microwave thermotherapy group benefited from therapy compared to the sham group. Of the sham group 50% had a favorable response after subsequent transurethral microwave thermotherapy. The 7 responders in the treatment group continued to improve during the subsequent 21 months.\n Transurethral microwave thermotherapy appears to be an effective, safe and durable treatment for some patients with nonbacterial prostatitis unresponsive to traditional therapy.", "Nonbacterial prostatitis is a common problem in young men. It is a disease that is often recurrent and each episode lasts for several months. Different causative mechanisms of the disease have been discussed, including identified and unidentified microorganisms, stone formation and psychological factors. We have demonstrated in a previous study that urinary reflux (as shown by a high creatinine concentration in prostatic fluid) occurs to a varying extent into the prostatic ducts, and this reflux has been related to prostatic pain and urate concentration in expressed prostatic secretion.\n We performed a paralled double-blind controlled study of the objective and subjective effects of allopurinol on patients with nonbacterial prostatitis. Twenty patients received placebo, 18 received 300 mg. allopurinol daily and 16 received 600 mg allopurinol daily for 240 days. All patients began medication at the same time regardless of whether the disease was in an active state. No side effects were noted in the treatment groups.\n Significant effects were noted on the concentrations of serum urate, urine urate, expressed prostatic secretion urate, expressed prostatic secretion xanthine and subjective discomfort.\n Allopurinol has a significant, positive effect on nonbacterial prostatitis. It is safe and worthy of trial for all at least a 3-month period at each episode to relieve the symptoms of nonbacterial prostatitis.", "To investigate whether treatment of inflammatory chronic pelvic pain syndrome (ICPPS) with finasteride has any influence on symptoms associated with ICPPS.\n Forty-one patients with ICPPS were randomized (1:3) to treatment with either placebo (25%, n = 10) or finasteride 5 mg daily (75%, n = 31 ) for 1 2 months. Efficacy was evaluated by analysis of symptomatic improvement through responses to symptom questionnaires, pain evaluation on an analytical visual scale, analgesic use as reported in patient diaries, urine flow and residual volume, and prostate volume.\n Prostatitis Symptom Severity Index and prostatism scores dropped significantly in patients in the finasteride group (P < 0.001 and P < 0.05, respectively). There were no statistically significant differences in pain between the groups. There were significant differences in the changes of prostate volume and in serum prostate-specific antigen concentrations between the finasteride and placebo groups (P < 0.03 and P < 0.02, respectively). The groups did not differ with regard to side effects.\n Our results indicate that finasteride has an effect in ICPPS. The mechanisms by which finasteride works in these patients are unclear and could not be solved in this pilot study, which had relatively few patients. A further trial with larger numbers is required to confirm these results.", "The National Institutes of Health (NIH) category III chronic prostatitis syndromes (nonbacterial chronic prostatitis and prostatodynia) are common disorders with few effective therapies. Bioflavonoids have recently been shown in an open-label study to improve the symptoms of these disorders in a significant proportion of men. The aim of this study was to confirm these findings in a prospective randomized, double-blind, placebo-controlled trial.\n Thirty men with category IIIa and IIIb chronic pelvic pain syndrome were randomized in a double-blind fashion to receive either placebo or the bioflavonoid quercetin 500 mg twice daily for 1 month. The NIH chronic prostatitis symptom score was used to grade symptoms and the quality-of-life impact at the start and conclusion of the study. In a follow-up unblind, open-label study, 17 additional men received 1 month of a supplement containing quercetin, as well as bromelain and papain (Prosta-O), which enhance bioflavonoid absorption.\n Two patients in the placebo group refused to complete the study because of worsening symptoms, leaving 13 placebo and 15 bioflavonoid patients for evaluation in the blind study. Both the quercetin and placebo groups were similar in age, symptom duration, and initial symptom score. Patients taking placebo had a mean improvement in NIH symptom score from 20.2 to 18.8 (not significant), while those taking the bioflavonoid had a mean improvement from 21.0 to 13.1 (P = 0.003). Twenty percent of patients taking placebo and 67% of patients taking the bioflavonoid had an improvement of symptoms of at least 25%. In the 17 patients who received Prosta-Q in the open-label study, 82% had at least a 25% improvement in symptom score.\n Therapy with the bioflavonoid quercetin is well tolerated and provides significant symptomatic improvement in most men with chronic pelvic pain syndrome.", "Transrectal microwave hyperthermia of the prostate was administered to 54 patients with chronic abacterial prostatitis or prostatodynia, who failed to respond to several courses of conventional therapies. Hyperthermia was delivered in 60-min long sessions with three randomly chosen regimens (1 session/week for 4 weeks; 1 session/week for 6 weeks; 2 sessions/week for 3 weeks). A prostatic temperature of 42.5 +/- 0.5 degrees C was maintained throughout the entire duration of each session. Patients were assessed pre- and postoperatively by scoring of subjective symptoms, uroflowmetry with flow nomograms, determination of residual urine volume, and transrectal ultrasonography of the prostate. At the long-term follow-up, the subjective symptom score was significantly improved in all patients. Fifty percent of the patients also reported an improvement of life quality, 47% reported their condition unchanged, and 3% reported deterioration, despite therapy. Urodynamic parameters improved but did not reach statistical significance. No major complications were encountered. Our preliminary data indicate that transrectal microwave hyperthermia of the prostate is a safe therapy that can be beneficial as a second line treatment in selected patients with recurring symptoms of abacterial prostatitis or prostatodynia, which do not respond to medical therapy.", "A double-blind, placebo-controlled study in 20 patients with 'prostatitis syndromes' and confirmed urodynamic abnormalities using the alpha 1-receptor-blocking compound alfuzosin is reported. Flow rate recordings are probably the most reliable and useful objective variables in this type of investigation. There is a significant beneficial effect in the group using an active compound concerning maximal flow (p = 0.01), flow time (p = 0.03) and time to maximal flow (p = 0.01). However, compared with the group using a placebo, only the change in the maximal flow rate appeared to be significantly different. Subjective effects were more pronounced in the alfuzosin group, but the spurious nature of the subjective observations is stressed. Based on objective parameters, alfuzosin seems to be effective compared to placebo in the treatment of these patients with micturition complaints of an irritative nature and urodynamic abnormalities, while only minor side effects were noticed.", "A therapeutical trial was conducted with pentosanpolysulphate (Elmiron) in 24 patients with chronic non-bacterial prostatitis. The study was double-blind and 10 patients received Elmiron 200 mg X 2 daily while 14 received a placebo. A beneficial effect (p less than 0.01) was registered on symptoms from muscles and joints. A side-effect observed was a tendency to develop diarrhoea in a few patients prone to gastrointestinal disturbances previously.", "In patients with chronic abacterial prostatitis, a double-blind trial of 3 months of treatment with minocycline 100 mg twice daily compared with diazepam 5 mg twice daily was undertaken. The percentage fall in polymorphonuclear leucocyte counts in the expressed prostatic secretions was much more marked after treatment with minocycline than with diazepam. Over a follow-up period of at least 12 months, further treatment was necessary in more patients originally treated with diazepam than with minocycline." ]

[ "15071401" ]

[ "Randomized controlled trial of aerosolized prostacyclin therapy in children with acute lung injury." ]

[ "To investigate whether aerosolized prostacyclin improves oxygenation in children with acute lung injury.\n Double-blind, randomized, and placebo-controlled trial.\n Pediatric intensive care unit at a university hospital.\n Fourteen children with acute lung injury defined by the criteria of an American-European Consensus Conference.\n Aerosolized prostacyclin (epoprostenol sodium) by stepwise increments of different doses (10, 20, 30, 40, and 50 ng x kg x min) vs. aerosolized normal saline (placebo).\n Before the start of the study, and before and after each dose of prostacyclin/placebo, the following variables were measured: arterial blood gases, heart rate, mean arterial blood pressure, and ventilator settings required. Changes in oxygenation were measured by calculation of the oxygenation index (mean airway pressure x 100 x Pao2/Fio2). After treatment with aerosolized prostacyclin, there was a significant 26% (interquartile range, 3%, 35%) improvement in oxygenation index at 30 ng x kg x min compared with placebo (p =.001). The response to prostacyclin was not the same in all children. We saw an improvement of > or = 20% in eight of 14 children (i.e., responders), and the number needed to treat was 1.8 (95% confidence interval, 1.2-3.2). No adverse effects were observed.\n Aerosolized prostacyclin improves oxygenation in children with acute lung injury. Future trials should investigate whether this treatment will positively affect outcome." ]

[ "14521531", "12648318", "11077932", "10102147", "16599101", "3058919", "14676592", "21261786", "11986453", "19416499", "9370894", "16155274", "20619853", "9894821", "17554249", "16954960", "11332926", "21592508", "12410197", "1694647", "10431116", "7651474", "10103334", "19068562" ]

[ "Efficacy of zinc supplementation on the severity and duration of diarrhea in malnourished Turkish children.", "Zinc supplementation in Brazilian children with acute diarrhoea.", "Impact of zinc supplementation in malnourished children with acute watery diarrhoea.", "Double-blind, randomized, controlled trial of zinc or vitamin A supplementation in young children with acute diarrhoea.", "Initiation of zinc treatment for acute childhood diarrhoea and risk for vomiting or regurgitation: a randomized, double-blind, placebo-controlled trial.", "A controlled trial on utility of oral zinc supplementation in acute dehydrating diarrhea in infants.", "Zinc with oral rehydration therapy reduces stool output and duration of diarrhea in hospitalized children: a randomized controlled trial.", "Probiotic, zinc and lactose-free formula in children with rotavirus diarrhea: are they effective?", "Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young children.", "Zinc and copper supplementation in acute diarrhea in children: a double-blind randomized controlled trial.", "Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea.", "Efficacy of zinc in young infants with acute watery diarrhea.", "Oral zinc for the treatment of acute gastroenteritis in Polish children: a randomized, double-blind, placebo-controlled trial.", "Impact of zinc supplementation on persistent diarrhoea in malnourished Bangladeshi children.", "Zinc supplementation in the management of shigellosis in malnourished children in Bangladesh.", "Zinc supplementation for the treatment of diarrhea in infants in Pakistan, India and Ethiopia.", "A randomized controlled clinical trial of zinc, vitamin A or both in undernourished children with persistent diarrhea in Bangladesh.", "Zinc, vitamin A, and micronutrient supplementation in children with diarrhea: a randomized controlled clinical trial of combination therapy versus monotherapy.", "Efficacy of zinc-fortified oral rehydration solution in 6- to 35-month-old children with acute diarrhea.", "Oral zinc supplementation in persistent diarrhoea in infants.", "Randomized, community-based trial of the effect of zinc supplementation, with and without other micronutrients, on the duration of persistent childhood diarrhea in Lima, Peru.", "Zinc supplementation in young children with acute diarrhea in India.", "Zinc supplementation in malnourished children with persistent diarrhea in Pakistan.", "Zinc supplementation in children with acute diarrhoea." ]

[ "Intervention trials have shown that zinc may be efficacious in treating acute diarrhea in children of developing countries. A double-blind placebo-controlled study was designed to evaluate the effects of zinc supplementation on the clinical course and duration of diarrhea in malnourished Turkish children.\n The study group comprised 40 subjects with low zinc levels (Group 1a) and 52 subjects with normal zinc levels (Group 1b). The control group was also comprised of two subgroups: 36 subjects with low zinc levels (Group 2a) and 54 subject with normal zinc levels (Group 2b). Forty-three percent of children in the study group and 40% of controls had low serum zinc levels (<14 micromol/L), and 43% of subjects in both groups had very low serum zinc concentrations (<10 micromol/L). The study group were given 20 mg zinc per day for 10 days and the control group were given 750 mg glucose per day as a placebo for 10 days.\n The mean duration of diarrhea was shorter and the percentage of children with consistent diarrhea for more than 3-7 days was lower in the study subgroups than in the control subgroups. Prolonged diarrhea was present in 12% of children in the study group, and in 44% and 37% of children in the hypozincemic and normozincemic control subgroups, respectively. The was no significant difference among the four subgroups of children in the number of cases with post-enrollment diarrhea of a duration of>14 days. Stool frequency over the first 4 days after enrollment was lower in children in the study group.\n It was concluded that zinc supplementation in malnourished children with acute diarrhea may reduce the severity and duration of diarrhea, especially in children with low zinc levels.", "Although oral rehydration therapy greatly reduces mortality from diarrhoeal diseases, it has little effect on stool frequency. However, there is mounting evidence that zinc is an effective adjunct to the treatment of diarrhoea, although few studies have examined its efficacy in Latin America. This study assessed the efficacy of zinc supplementation in children with acute diarrhoea in Brazil. The study was a double-blind, placebo-controlled, randomised, clinical trial in children <5 years of age attending emergency services in Sergipe, Brazil. Subjects received zinc or vitamin C as placebo. There was a marked reduction in the duration of the diarrhoea (1.1 vs 2.6 days) and of watery stools in the zinc-supplemented group. The efficacy of zinc was independent of the presence of viral enteropathogens in the stools. It is concluded that, similar to studies in India and Bangladesh, zinc could be an important adjunct for treating acute diarrhoea in Brazilian children.", "A double-blind, randomized, controlled clinical trial was conducted on 80 malnourished children with acute dehydrating diarrhoea to evaluate the efficacy of oral supplementation of zinc as an adjunct therapy to oral rehydration solution (ORS). After decoding it was observed that 44 children received zinc sulphate (177 mg/kg/day in three divided doses equivalent to 40 mg elemental zinc) in a syrup form and 36 children received only syrup placebo. Clinical parameters and microbiological findings of stool samples were comparable in the two groups at the time of enrollment. All the children (100 per cent) in the zinc supplemented group and 32 (89 per cent) children in the placebo group recovered within 5 days of hospitalization (p = 0.04). The zinc supplemented group had a significantly shorter duration of diarrhoea (70.4 +/- 10.0 vs. 103.4 +/- 17.1 h; p = 0.0001), passed less liquid stool (1.5 +/- 0.7 vs. 2.4 +/- 0.7kg; p=0.0001), consumed less oral rehydration solution (2.5 +/- 1.0 vs. 3.6 +/- 0.8 litre; p = 0.0001) and other liquids (867.0 +/- 466.1 vs. 1354.7 +/- 675.6 ml; p = 0.0001) as compared to the placebo group. Our findings suggest that zinc supplementation as an adjunct therapy to ORS has beneficial effects on the clinical course of dehydrating acute diarrhoea.", "In a double-blind, controlled trial with a factorial design, 684 patients (aged 6 months to 2 y; excludes 6 early dropouts) with acute watery diarrhoea of 3 d or less and some dehydration, who were attending a hospital, were randomly assigned to 4 groups to receive: (a) vitamin A 4500 microg retinol equivalent daily for 15 d; (b) 14.2 mg elemental zinc as acetate for the first 417 patients and 40 mg of the remaining 273 patients randomized to this group for 15 d; (c) both vitamin A 4500 microg retinol equivalent and zinc at the above doses daily for 15 d; or (d) placebo mixtures for 15 d. Patients were observed in the hospital for 24 h and followed up at home for 15 d. All received ascorbic acid 30 mg with each dose of medicine or placebo. Zinc supplementation was associated with a reduced duration of diarrhoea (13%, p = 0.03) and markedly reduced rate (43%, p = 0.017) of prolonged diarrhoea (>7 d). Vitamin A supplementation was associated with a nonsignificant trend for reduced rate of prolonged diarrhoea (p = 0.089). In conclusion, zinc supplementation as adjunct therapy had a substantial impact on the rate of prolonged diarrhoea and some impact on duration and may be beneficial in children with diarrhoea in developing countries.", "The childhood diarrhoea-management guidelines of the World Health Organization/United Nations Children's Fund (WHO/UNICEF) now include zinc treatment, 20 mg per day for 10 days. To determine if a dispersible zinc sulphate tablet formulation is associated with increased risk of vomiting or regurgitation following the initial, first treatment dose, a double-blind, placebo-controlled randomized clinical trial was carried out in the Dhaka hospital of ICDDR,B: Centre for Health and Population Research (n=800) and in an adjacent NGO outpatient clinic (n=800). Children were randomized to one of three groups: no treatment, placebo, or zinc sulphate tablet (20 mg). They were then observed for 60 minutes, and all vomiting or regurgitation episodes were recorded. When compared with placebo, zinc treatment resulted in an attributable risk increase of 14% for vomiting and 5.2% for regurgitation. The median time to vomiting among those receiving zinc was 9.6 minutes and was limited to one episode in 91.2% of the cases. Overall, the proportion of 60-minute post-treatment vomiting attributable to zinc, placebo, and the illness episode was estimated to be 40%, 26%, and 34% respectively. The dispersible zinc sulphate tablet formulation at a dose of 20 mg is associated with increased risks of vomiting and regurgitation. Both are transient side-effects.", "A controlled, randomized trial was conducted in 50 infants with acute dehydrating diarrhea to evaluate the effect of oral zinc supplementation in acute diarrhea. After completion of rehydration, 25 infants in Group A received oral zinc sulfate (20 mg elemental zinc twice daily) and an equal number in Group B were given placebo (glucose). Both groups were comparable with respect to various initial characteristics including nutritional status, diarrheal disease, serum alkaline phosphatase, and serum and rectal mucosal zinc content. During therapy all the assessed parameters of zinc status (serum alkaline phosphatase and serum and rectal zinc) recorded significant elevation and reduction in Groups A and B, respectively. At recovery the zinc status of Group A was significantly better and was nearer that of healthy controls. The diarrheal duration and frequency in the zinc-supplemented group were lower, but the differences were not significant (0.05 less than p less than 0.1). However, when only subjects with relatively severe initial zinc depletion (rectal zinc lower than the 15th percentile of healthy controls; 11 in Group A and 14 in Group B) were considered, the diarrheal duration and frequency were significantly (p less than 0.05 and p less than 0.01, respectively) lower in the zinc-supplemented cases. Weight gain in both groups was similar. It is concluded that oral zinc administration in acute diarrhea can replenish body zinc status and this may shorten the diarrheal duration and frequency in children with relatively severe zinc depletion.", "The authors evaluated the effect of zinc treatment as an adjunct to oral rehydration therapy on stool output and diarrheal duration in children with acute noncholera diarrhea with dehydration.\n This double-blind, randomized, controlled trial was conducted at two urban hospitals in New Delhi. A total of 287 dehydrated male patients, ages 3 to 36 months, with diarrhea for <or= 72 hours were enrolled. They were assigned to zinc or placebo by a randomization scheme stratified by age (<or= or >12 months) and weight for height (65%-80% or >80% National Centre for Health Statistics median). Participants in the zinc group received 15 mg (<or=12 months) or 30 mg (>12 months) elemental zinc daily in three divided doses for 14 days. The main outcome measures were stool output and diarrheal duration.\n Zinc treatment reduced total stool output (ratio of geometric means, 0.69; 95% confidence interval [CI]: 0.48, 0.99) and stool output per day of diarrhea (ratio of geometric means, 0.76; 95% CI: 0.59, 0.98). The risk of continued diarrhea was lower (relative hazards, 0.76; 95% CI: 0.59, 0.97) and the proportion of diarrheal episodes lasting >or= 5 days (odds ratio, 0.49; 95% CI: 0.25, 0.97) or >or= 7 days was less (odds ratio, 0.09; 95% CI: 0.01, 0.73) in the zinc group.\n This study demonstrates a beneficial effect of zinc administered during acute diarrhea on stool output, diarrheal duration, and proportion of episodes lasting more than 7 days. The effects are large enough to merit routine use of zinc during acute diarrhea in developing countries.", "The aim of the present study was to evaluate the effectiveness of zinc, probiotic bacteria, and lactose-free formula and their different combinations in the treatment of rotavirus diarrhea in young children.\n Eight different treatment groups were formed: group 1, 60 patients receiving Saccharomyces boulardii; group 2, 60 patients receiving zinc; group 3, 60 patients receiving lactose-free formula; group 4, 60 patients receiving S. boulardii plus zinc; group 5, 60 patients receiving S. boulardii plus lactose-free formula; group 6, 60 patients receiving zinc plus lactose-free formula; group 7, 60 patients receiving S. boulardii plus zinc plus lactose-free formula; group 8, 60 patients receiving only oral and/or parenteral rehydration solutions.\n No statistically significant differences were found in the time to resolution of fever after intervention between the treatment groups and the control group. The time to resolution of vomiting was significantly lower in group 4 compared with groups 1 and 5. The duration of diarrhea was significantly reduced in groups 2 and 4 compared to control. A statistically significant difference in the duration of hospitalization was observed for the groups 2 and 4 in comparison to the control group.\n A different combination of adjunct therapies did not seem to bring additional value to rehydration therapy in children with rotavirus diarrhea except for in those receiving only zinc and zinc plus S. boulardii. Further studies are required to determine the optimal protocol of adjunct therapy use in children with rotavirus diarrhea.\n © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.", "Intervention trials have shown that zinc is efficacious in treating acute diarrhea in children of developing countries. In a randomized, placebo-controlled trial, we assessed the effectiveness and efficacy of giving 3 Recommended Daily Allowances of elemental zinc to 6- to 35-month-old children with acute diarrhea.\n Seventeen hundred ninety-two cases of acute diarrhea in Nepalese children were randomized to 4 study groups. Three groups were blinded and the children supplemented daily by field workers with placebo syrup, zinc syrup, or zinc syrup and a massive dose of vitamin A at enrollment. The fourth group was open and the caretaker gave the children zinc syrup daily. Day-wise information on morbidity was obtained by household visits every fifth day.\n The relative hazards for termination of diarrhea were 26% (95% confidence interval [CI]: 8%, 46%), 21% (95% CI: 4%, 38%), and 19% (95% CI: 2%, 40%) higher in the zinc, zinc-vitamin A, and zinc-caretaker groups, respectively, than in the placebo group. The relative risks of prolonged diarrhea (duration >7 days) in these groups were 0.57 (95% CI: 0.38, 0.86), 0.53 (95% CI: 0.35, 0.81), and 0.55 (0.37, 0.84); zinc accordingly reduced the risk of prolonged diarrhea with 43% to 47%. Five percent and 5.1% of all syrup administrations were followed by regurgitation in the zinc and zinc-vitamin A group, respectively, whereas this occurred after only 1.3% of placebo administrations. Vomiting during diarrhea was also more common in children receiving zinc.\n Three Recommended Daily Allowances of zinc given daily by caretakers or by field workers substantially reduced the duration of diarrhea. The effect of zinc was not dependent on or enhanced by concomitant vitamin A administration.", "Diarrhea causes an estimated 2.5 million child deaths in developing countries each year, 35% of which are due to acute diarrhea. Zinc and copper stores in the body are known to be depleted during acute diarrhea. Our objectives were to evaluate the efficacy of zinc and copper supplementation when given with standard treatment to children with acute watery or bloody diarrhea.\n We conducted a double-blind randomized controlled clinical trial in the Department of Pediatrics at Indira Gandhi Government Medical College Nagpur, India. Eight hundred and eight children aged 6 months to 59 months with acute diarrhea were individually randomized to placebo (Pl), zinc (Zn) only, and zinc and copper (Zn+Cu) together with standard treatment for acute diarrhea.\n The mean duration of diarrhea from enrollment and the mean stool weight during hospital stay were 63.7 hours and 940 grams, respectively, and there were no significant differences in the adjusted means across treatment groups. Similarly, the adjusted means of the amount of oral rehydration solution or intravenous fluids used, the proportion of participants with diarrhea more than 7 days from onset, and the severity of diarrhea indicated by more than three episodes of some dehydration or any episode of severe dehydration after enrollment, did not differ across the three groups.\n The expected beneficial effects of zinc supplementation for acute diarrhea were not observed. Therapeutic Zn or Zn and Cu supplementation may not have a universal beneficial impact on the duration of acute diarrhea in children.", "To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea.\n Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks.\n A diarrhoeal disease hospital in Dhaka, Bangladesh.\n 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded.\n Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation.\n Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital.\n Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.", "Recent studies reported that zinc significantly reduced the duration and volume of acute watery diarrhea in children aged > or = 4 mo, but there were no data specifically on infants aged < 6 mo.\n This study investigated the effect of zinc on the duration of illness and the stool quantity in acute watery diarrhea of infants aged 1-6 mo by comparing a 20 mg Zn/d dose with a 5 mg Zn/d dose.\n Infants hospitalized with at least some dehydration (by World Health Organization classification) were enrolled in a double-blind, randomized, placebo-controlled trial. Infants were randomly assigned to receive 20 mg Zn (acetate)/d, 5 mg Zn/d, or placebo for the duration of illness.\n Two hundred seventy-five infants were enrolled between 20 September 1998 and 18 December 2000. Neither diarrhea duration nor mean stool volume differed between groups. There were no significant differences in fluid intake, the need for unscheduled intravenous fluid, weight gain, or vomiting rates between the groups.\n Zinc supplementation did not affect diarrhea duration or stool volume in young infants. Young infants tolerated both zinc doses. A beneficial effect on subsequent illness cannot be ruled out.", "To evaluate the efficacy and safety of zinc in the treatment of acute gastroenteritis (AGE) in children in Poland.\n Children aged 3 to 48 months with AGE were enrolled in a randomized, double-blind, placebo-controlled trial in which they received zinc sulfate (10 or 20 mg/day depending on age) or placebo for 10 days. A total of 141 of 160 children recruited were available for intention-to-treat analysis. The primary outcome was the duration of diarrhea.\n In the experimental group (n = 69) compared with the control group (n = 72), there was no significant difference in the duration of diarrhea (P > .05). Similarly, there was no significant difference in the groups in secondary outcome measures such as stool frequency on days 1, 2, and 3, vomiting frequency, intravenous fluid intake, and the number of children with diarrhea lasting >7 days.\n Children living in a country where zinc deficiency is rare do not appear to benefit from the use of zinc in the treatment of AGE.\n Copyright © 2010 Mosby, Inc. All rights reserved.", "To evaluate the impact of zinc supplementation on the clinical recovery and body weight of children with persistent diarrhoea, a randomized, double-blind, controlled trial was conducted in 190 children with persistent diarrhoea aged between 3 and 24 months. Children were randomly allocated to receive either zinc (20 mg d(-1)) syrup with multivitamin (2 x RDA) or multivitamin alone in three divided daily doses for 2 weeks. The trial was conducted in a diarrhoeal disease hospital in Dhaka, Bangladesh. Duration until clinical recovery (d), impact on body weight and serum zinc level after 2 weeks of zinc supplementation were recorded. The duration of illness was significantly reduced (33%) with zinc supplementation among children who were underweight (< or =70% wt/age, p = 0.03). Supplemented male children also had a significant reduction (27%) in duration for recovery compared with unsupplemented children (p = 0.05). From baseline to convalescence, zinc-supplemented children maintained their serum zinc concentration (13.4 vs 13.6 micromol l(-1)), whereas unsupplemented children had a decrease in serum zinc after the 2 weeks of diarrhoea (13.6 vs 11.8 micromol l(-1),p < 0.03). The mean body weight of the children in the supplemented group was maintained (5.72 vs 5.70 kg, p = 0.62) during hospitalization, unlike that of the control group, in which there was a reduction in body weight (5.75 vs 5.67 kg, p = 0.05). Five children in the unsupplemented group and one child in the zinc-supplemented group died during the 2 weeks of supplementation (p = 0.06). Zinc supplementation in persistent diarrhoea significantly reduced the length of the recovery period in malnourished children and prevented a fall in body weight and serum zinc concentration, indicating that zinc is a beneficial therapeutic strategy in this high-risk childhood illness.", "To assess the impact of zinc supplementation on clinical recovery, weight gain and subsequent growth and morbidity in moderately malnourished children with shigellosis.\n A randomized, double-blind, controlled trial.\n Dhaka hospital of ICDDR,B: Centre for Health and Population Research, Dhaka, Bangladesh.\n Fifty-six moderately malnourished children, aged 12-59 months with culture-proven shigellosis.\n Subjects were randomly allocated to receive zinc (20 mg/day elemental) in multivitamin syrup (intervention) or multivitamin syrup without zinc (control) in two equally divided doses daily for 2 weeks. All children received pivmecillinam in a dose of 15 mg/kg every 6 h for 5 days. After supplementation, children were followed in their respective homes every 2 weeks for 6 months.\n Children receiving zinc recovered from acute illness significantly faster than the control children (P<0.05). The medians time (days) to recovery and disappearances of blood and mucous were significantly 50% shorter in the zinc-supplemented group compared to the control group. The mean body weight of zinc supplemented children increased significantly from 8.8 kg on admission to 9.2 kg (P<0.01) at recovery, which was not observed in the control children (from 9.3 to 9.6 kg; P=0.12). During the 6-month follow-up period, zinc-supplemented children had significantly fewer mean episodes of diarrhoea compared to the control children (2.2 vs 3.3; P=0.03).\n Zinc supplementation significantly shortens the duration of acute shigellosis, promotes better weight gain during recovery and reduces diarrhoeal morbidity during the subsequent 6 months.", "This randomized, placebo controlled trial was designed to assess the safety and efficacy of 10-mg zinc supplementation for the treatment of acute diarrhea in infants.\n A total of 1110 infants aged 28 days to 5 months with acute diarrhea were enrolled and randomized to receive either zinc (n = 554) or placebo (n = 556) for 14 days. Diarrhea history, anthropometric status, breast-feeding status and socioeconomic indicators were assessed at baseline. The homes of all infants were visited every 3 days until the diarrhea episode was over. The number of stools, presence of blood and additional illnesses were recorded daily.\n The geometric mean duration of the diarrhea episode was 0.21 days longer among infants receiving zinc versus those receiving placebo, but this was not statistically significant and no difference was observed after controlling for sex, exclusive breast-feeding and length for age Z score. There were no differences in any subgroup (ie, sex, baseline length for age Z score, exclusive breast-feeding or site after controlling for the remaining subgroup variables). There were no differences in reported stool frequency or among the proportion of episodes lasting longer than 7 days. Rates of vomiting were similar in the zinc and placebo groups.\n Young infants do not appear to benefit from zinc supplementation for the treatment of diarrhea.", "In a double-blind randomized controlled clinical trial, moderately malnourished Bangladeshi children (61-75% of the median weight/age) were studied for the effect of zinc and/or vitamin A supplementation on the clinical outcome of persistent diarrhea. Children 6 mo to 2 y of age with diarrhea for more than 14 d were randomly allocated into 4 groups of 24 receiving a multivitamin syrup and (i) zinc (20 mg elemental), (ii) vitamin A, (iii) both zinc and vitamin A, or (iv) neither, in 2 doses daily for 7 d. Clinical data on recovery and on stool output, consistency and frequency were recorded for 7 d, and weight change from day 1 to day 7 was assessed. The baseline characteristics of the four study groups were comparable. The mean daily stool outputs from days 2 to 7 of therapy were significantly less in the zinc and zinc plus vitamin A groups, but not in the vitamin A group, in comparison with the control group. In children receiving zinc, the cumulative stool weight in the 7 d was 39% less than in the control group (p < 0.001) and 32% less than in the vitamin A group (p = 0.006). The cumulative stool weight in the zinc plus vitamin A group was 24% less than in the control group (p < 0.001), but the 14% lower output than in the vitamin A group was not statistically different. The change in body weight over the 7 d study period was significantly different between the group receiving zinc and the control group (+111 g vs -90 g, p = 0.045). The rate of clinical recovery of children within 7 d was significantly greater in the zinc group (88%) compared with the control group (46%, p = 0.002) or vitamin A group (50%, p = 0.005), but not statistically different from the zinc plus vitamin A group (67%, p = 0.086). Conclusion: The results indicate that zinc, but not vitamin A, supplementation in persistent diarrhea reduces stool output, prevents weight loss and promotes earlier recovery.", "To compare the clinical efficacy of supplementation of zinc, zinc plus vitamin A, and zinc plus combination of micronutrients and vitamins (iron, copper, selenium, vitamin B(12), folate, and vitamin A) on acute diarrhea in children.\n This was a double-blind, randomized, placebo-controlled trial. Children aged 6 to 24 months with diarrhea and moderate dehydration were randomized to receive zinc plus placebo vitamin A (group 1), zinc plus other micronutrients plus vitamin A (group 2), zinc plus vitamin A (group 3), or placebo (group 4) as an adjunct to oral rehydration solution. Duration, volume of diarrhea, and consumption of oral rehydration solution were compared as outcome variables within the supplemented groups and with the placebo group.\n The 167 study subjects included 41 in group 1, 39 in group 2, 44 in group 3, and 43 in group 4. All 3 supplemented groups demonstrated a significant reduction in outcome variables (P < .0001) compared with the placebo group. Group 3 had the lowest reduction of outcome variables and group 2 had a speedy recovery, but differences among the supplemented groups were not statistically significant.\n Supplementation with a combination of micronutrients and vitamins was not superior to zinc alone, confirming the clinical benefit of zinc in children with diarrhea.\n Copyright © 2011 Mosby, Inc. All rights reserved.", "To determine the efficacy of zinc-fortified oral rehydration salts solution (ORS) in comparison to ORS without zinc in 6- to 35-month-old urban children with acute diarrhea not sick enough to be hospitalized.\n Double-blind, randomized, controlled trial.\n Children (n = 1219) with acute diarrhea were randomly assigned to one of 3 groups. The first group received a zinc syrup (15 mg zinc to 6- to 11-month-old children and 30 mg to 12- to 35-month-old children), the second group received zinc premixed with ORS (40 mg/L), and the control children received ORS only. Households were visited twice weekly until recovery.\n The total number of stools was lower in the zinc-ORS group (rate ratio, 0.83; 95% CI, 0.71-0.96), as was the proportion of children with watery stools (odds ratio, 0.61; 95% CI, 0.39-0.95), compared with the control group; there was no significant effect on diarrheal duration. ORS intake and proportion of children with vomiting were not significantly different between the zinc-ORS and control groups. The zinc syrup group had lower diarrheal duration (relative hazards, 0.89; 95% CI, 0.80-0.99) and total stools (rate ratio, 0.73; 95% CI, 0.70-0.77) than control children.\n Zinc-ORS was moderately efficacious in reducing the severity of acute diarrhea without increasing vomiting or reducing ORS intake.", "A controlled randomized trial was conducted in 40 infants (6-18 months old) with persistent diarrhoea (greater than 2 weeks' duration) to evaluate the effect of oral zinc supplementation. After completion of rehydration, 20 infants in group A received oral zinc sulphate (20 mg elemental zinc twice daily) and an equal number in group B were given a placebo (glucose). Each child was given oral nalidixic acid and a similar milk-free feeding schedule. Both the groups were comparable with respect to various initial characteristics including nutrition, diarrhoeal disease, serum alkaline phosphatase and serum and rectal mucosal zinc content. During therapy, all the assessed parameters of zinc status (serum alkaline phosphatase and serum and rectal zinc) recorded significant elevation and reduction in groups A and B, respectively. At recovery, the zinc status of group A was significantly higher than that of group B. The diarrhoeal duration and frequency in the zinc-supplemented group were lower but the differences were not statistically significant (p = 0.078 and p = 0.076, respectively). Weight gain in both groups was comparable. It is concluded that in persistent diarrhoea there is depletion of zinc with the progression of disease and oral zinc administration can improve the zinc status. The possible anti-diarrhoeal effect of zinc, however, merits further study.", "To determine whether supplemental zinc, with or without additional micronutrients, affects the severity and duration of persistent childhood diarrhea and the rate of nutritional recovery.\n The study was a community-based, double-blind, randomized trial implemented in a shanty town in Lima, Peru. Children aged 6 to 36 months with persistent (>/=14 days) diarrhea received daily, for 2 weeks, a placebo (group P, n = 136) or a supplement of 20 mg of zinc, either with (group Z+VM, n = 137) or without (group Z, n = 139) additional vitamins and minerals. Symptoms of illness were recorded daily, and biochemical and anthropometric assessments were completed at baseline and on day 15.\n The treatment groups were similar at baseline with regard to the characteristics of the presenting episode, anthropometric data, and plasma zinc concentration. The children consumed, on average, 95% (group P), 94% (group Z), or 88% (group Z+VM) of the supplement (P <.001). The plasma zinc concentration did not change significantly from baseline to day 15 in group P (4 microg/dL) but increased by 38 microg/dL in group Z and 14 microg/dL in group Z+VM. The median duration of diarrhea after starting treatment was 1 day; among children who continued to have diarrhea, there was a significant effect of treatment on diarrheal duration (P =.04, analysis of covariance). Specifically, the duration of illness was significantly reduced by 28% in children in group Z (P =.01) and by 33% in girls in group Z+VM (P =.04). There were no differences in the severity of the episode by treatment group.\n There was a significant reduction in the duration of persistent diarrhea in selected subgroups of zinc-supplemented ambulatory patients in this population.", "In developing countries the duration and severity of diarrheal illnesses are greatest among infants and young children with malnutrition and impaired immune status, both factors that may be associated with zinc deficiency. In children with severe zinc deficiency, diarrhea is common and responds quickly to zinc supplementation.\n To evaluate the effects of daily supplementation with 20 mg of elemental zinc on the duration and severity of acute diarrhea, we conducted a double-blind, randomized, controlled trial involving 937 children, 6 to 35 months of age, in New Delhi, India. All the children also received oral rehydration therapy and vitamin supplements.\n Among the children who received zinc supplementation, there was a 23 percent reduction (95 percent confidence interval, 12 percent to 32 percent) in the risk of continued diarrhea. Estimates of the likelihood of recovery according to the day of zinc supplementation revealed a reduction of 7 percent (95 percent confidence interval, -9 percent to +22 percent) in the risk of continued diarrhea during days 1 through 3 and a reduction of 38 percent (95 percent confidence interval, 27 percent to 48 percent) after day 3. When zinc supplementation was initiated within three days of the onset of diarrhea, there was a 39 percent reduction (95 percent confidence interval, 7 percent to 61 percent) in the proportion of episodes lasting more than seven days. In the zinc-supplementation group there was a decrease of 39 percent (95 percent confidence interval, 6 percent to 70 percent) in the mean number of watery stools per day (P = 0.02) and a decrease of 21 percent (95 percent confidence interval, 10 percent to 31 percent) in the number of days with watery diarrhea. The reductions in the duration and severity of diarrhea were greater in children with stunted growth than in those with normal growth.\n For infants and young children with acute diarrhea, zinc supplementation results in clinically important reductions in the duration and severity of diarrhea.", "To evaluate the potential benefit of dietary supplementation of a rice-lentil (Khitchri) and yogurt diet with 3 mg/kg/d of elemental zinc (as zinc sulfate) in hospitalized malnourished children (age 6-36 months) with persistent diarrhea for 14 days.\n Randomized, double-blind placebo-controlled trial.\n Nutrition Research Ward at the National Institute of Child Health, Karachi, Pakistan, where children were admitted for 14 days of inpatient supervised rehabilitation.\n Primary outcome: overall weight gain by day 14. Secondary outcomes: overall energy intake, stool output, time to diarrheal recovery and weight gain (>/=3 days), plasma zinc, copper, prealbumin, and insulin-like growth factor-1.\n Of 87 children randomized for supplementation with either zinc or placebo, the two groups were comparable at admission in terms of severity and duration of diarrhea, as well as nutritional and anthropometric parameters. The overall weight gain, stool volume, stool frequency, as well as the time taken for diarrheal recovery or steady weight gain, were comparable for both supplemented children and controls. Supplemented children had a significant improvement in plasma zinc levels and serum alkaline phosphatase by day 14 of therapy in comparison with controls. Plasma copper levels were low in both groups at admission and although an increase was seen in control children, levels decreased further after zinc supplementation. There was no significant difference between the two groups for hemoglobin, serum albumin, prealbumin, and plasma insulin-like growth factor-1 increments during the course of therapy. Evaluation of primary and secondary outcome criteria among the subset of children with plasma zinc levels <60 microg/d at admission did not reveal any significant differences.\n Although there was satisfactory recovery in malnourished children with persistent diarrhea receiving the Khitchri-yogurt diet, there was no evidence of improved weight gain or acceleration of recovery from diarrhea with zinc supplementation. In contrast, the reduction in plasma copper levels in zinc-supplemented malnourished children suggests that caution should be exercised in supplementing severely malnourished children with zinc alone.", "In Nigeria, diarrhoeal disease is second only to malaria as a cause of death the under 5 age group. This study was aimed at assessing the benefit or otherwise of zinc supplement in acute diarrhoea.\n This was a multi-centred randomized double blind controlled study. Children with acute diarrhoea aged between 6 and 24 months were randomized into zinc supplemented and placebo groups. Plasma zinc levels were analyzed at enrollment and at the end of the study. The children were reviewed for the next three months from the time of enrollment.\n The mean plasma zinc levels at baseline and at the end of the study were 0.06 +/- 0.04 and 0.067 +/- 0.03 ppm in the zinc supplemented group and 0.11 +/- 0.02 and 0.05 +/- 0.03 ppm in the control group. The differences were not statistically significant. The zinc supplemented group had an average weight gain of 1.1 kg as against 0.73 kg (p = 0.00) for the control group in the study period. No adverse effect was reported on account of zinc supplementation.\n Zinc supplementation is beneficial in acute diarrhoea as observed in this study." ]

[ "12061361", "7838642" ]

[ "Changes in cerebral, renal and mesenteric blood flow velocity during continuous and bolus infusion of indomethacin.", "Continuous versus multiple rapid infusions of indomethacin: effects on cerebral blood flow velocity." ]

[ "Vasoconstriction induced by bolus injection of indomethacin reduces organ perfusion and has been related to the well-known side effects of indomethacin given for closure of the patent ductus arteriosus (PDA). The aim of the study was to compare the changes in cerebral, renal and mesenteric blood flow velocities after continuous infusion versus bolus injection of indomethacin for closure of the PDA. Thirty-two preterm infants (range 26-35 wk gestational age) with PDA were randomly assigned to receive the same amount of indomethacin either as three bolus injections (n = 14) or as a continuous infusion (n = 18) over 36 h. Blood flow velocities were measured in the internal carotid, right renal and superior mesenteric arteries at baseline and serially at 10, 30, 60 and 120 min and 12, 24, 36 and 48 h after the start of indomethacin treatment. There were no differences in blood flow velocities between both groups at baseline. During continuous infusion of indomethacin there was no significant change in the cerebral, renal and mesenteric blood flow velocities, whereas the flow velocities in the infants receiving bolus injections decreased significantly during the first 2 h after indomethacin administration in all arteries measured. There was a transient, but significant reduction in urine output after bolus injection of indomethacin. Conclusion: In contrast to bolus injections, decrease of organ blood flow and impairment of urine output do not accompany continuous infusion of indomethacin over 36 h.", "Therapeutic administration of indomethacin for patent ductus arteriosus (PDA) closure has been documented to decrease cerebral blood flow velocity which may be harmful to the vulnerable premature neonate. We have therefore compared the effects of administering indomethacin by rapid injection versus slow, continuous indomethacin infusion at the same total therapeutic dose on middle cerebral artery (MCA) systolic and diastolic flow velocity, resistance index, and cerebral blood flow (as reflected by the integrated area under the curve).\n Premature neonates (< 1750 g) documented echocardiographically to have a PDA were randomized to receive indomethacin either by three rapid injection doses or by continuous intravenous infusion over the ensuing 36 hours, providing an equivalent total dose. Echocardiograms and transcranial color flow mapping of the MCA flow velocity were measured at baseline and serially following initiation of therapy in both groups. Effects on cerebral blood flow velocity are presented.\n Eighteen infants [rapid injection-1.2 +/- 0.3 kg (n = 9) and continuous-1.1 +/- 0.2 kg (n = 9)] were studied. In the rapid injection treated infants decreased flow velocity in the MCA as manifested by abrupt, significant decreases in systolic (to 70 +/- 8% baseline) and diastolic (to 65 +/- 13% baseline) flow velocity and area under the curve (to 60 +/- 10% of baseline) were evident by 4 minutes and progressed to 30 minutes after treatment initiation. These changes were not observed in the group treated with continuous indomethacin. Both therapeutic modalities were equally successful in closing the ductus, although the numbers are too small to definitively determine therapeutic efficacy.\n Slow, continuous infusion eliminated the decrease in cerebral flow velocity and appears to be effective in closing the PDA." ]

[ "3182439", "1524078", "15881476", "7861197", "10566563", "15365537", "17362810", "3484423", "1827106", "10399110", "17011409", "8118565", "15072030", "10064632", "9569434", "9309369", "19944891", "1505371", "4989705", "9721958", "10845431", "8737130", "8763594", "8997555", "14750614", "10214783", "14503094", "8760738", "8539546", "9579718", "9923060", "12936972", "11452678", "9950107", "9916606", "9855324", "15823766", "10839487", "8204290", "11911557", "6379803", "8360132", "9602984", "15679233", "9078199", "15689289", "18559163", "12709801", "9210677", "16087013", "8111512", "8818848", "8313865", "1799916" ]

[ "Comparison of spiramycin and doxycycline in the empirical treatment of acute sinusitis: preliminary results.", "Clinical comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of patients with acute bacterial maxillary sinusitis.", "Once daily clarithromycin extended-release vs twice-daily amoxicillin/clavulanate in patients with acute bacterial sinusitis: a randomized, investigator-blinded study.", "Therapeutic efficacy and tolerability of brodimoprim in comparison with doxycycline in acute sinusitis in adults.", "Comparison of moxifloxacin and cefuroxime axetil in the treatment of acute maxillary sinusitis. Sinusitis Infection Study Group.", "Efficacy and safety of oral telithromycin once daily for 5 days versus moxifloxacin once daily for 10 days in the treatment of acute bacterial rhinosinusitis.", "Moxifloxacin vs amoxicillin/clavulanate in the treatment of acute sinusitis.", "Acute bacterial sinusitis. Minocycline vs amoxicillin.", "The comparative efficacy and safety of clarithromycin and amoxycillin in the treatment of outpatients with acute maxillary sinusitis.", "Efficacy and safety of oral levofloxacin compared with clarithromycin in the treatment of acute sinusitis in adults: a multicentre, double-blind, randomized study. The Canadian Sinusitis Study Group.", "Randomized double-blind study comparing 7- and 10-day regimens of faropenem medoxomil with a 10-day cefuroxime axetil regimen for treatment of acute bacterial sinusitis.", "Cefaclor vs amoxicillin in the treatment of acute, recurrent, and chronic sinusitis.", "An open label, randomized comparative study of levofloxacin and amoxicillin/clavulanic acid in the treatment of purulent sinusitis in adult Thai patients.", "Comparison of the effectiveness of levofloxacin and amoxicillin-clavulanate for the treatment of acute sinusitis in adults.", "Antibiotic treatment of patients with mucosal thickening in the paranasal sinuses, and validation of cut-off points in sinus CT.", "Efficacy and tolerability of ceftibuten versus amoxicillin/clavulanate in the treatment of acute sinusitis.", "Azithromycin extended release vs amoxicillin/clavulanate: symptom resolution in acute sinusitis.", "Loracarbef (LY 163892) vs amoxicillin/clavulanate in bacterial maxillary sinusitis.", "Treatment of acute maxillary sinusitis. A comparison of four different methods.", "Azithromycin versus placebo in acute infectious rhinitis with clinical symptoms but without radiological signs of maxillary sinusitis.", "A comparison of the safety and efficacy of moxifloxacin (BAY 12-8039) and cefuroxime axetil in the treatment of acute bacterial sinusitis in adults. The Sinusitis Study Group.", "Sparfloxacin versus cefuroxime axetil in the treatment of acute purulent sinusitis. Sinusitis Study Group.", "[Clarithromycin versus amoxicillin-clavulanic acid in the treatment of acute maxillary sinusitis in adults].", "Efficacy and safety of azithromycin versus phenoxymethylpenicillin in the treatment of acute maxillary sinusitis.", "A comparison of the efficacy of telithromycin versus cefuroxime axetil in the treatment of acute bacterial maxillary sinusitis.", "Double-blind comparative trial of ciprofloxacin versus clarithromycin in the treatment of acute bacterial sinusitis. Sinusitis Infection Study Group.", "Efficacy and tolerability of telithromycin for 5 or 10 days vs amoxicillin/clavulanic acid for 10 days in acute maxillary sinusitis.", "Randomised, double blind, placebo controlled trial of penicillin V and amoxycillin in treatment of acute sinus infections in adults.", "Treatment of acute maxillary sinusitis--comparing cefpodoxime proxetil with amoxicillin.", "Comparison of roxithromycin with co-amoxiclav in patients with sinusitis.", "Cefuroxime axetil versus clarithromycin in the treatment of acute maxillary sinusitis.", "Randomized double-blind study comparing 3- and 6-day regimens of azithromycin with a 10-day amoxicillin-clavulanate regimen for treatment of acute bacterial sinusitis.", "Moxifloxacin versus amoxicillin clavulanate in the treatment of acute maxillary sinusitis: a primary care experience.", "Azithromycin versus amoxicillin/clavulanate in the treatment of acute sinusitis.", "Efficacy and tolerability of cefprozil versus amoxicillin/clavulanate for the treatment of adults with severe sinusitis.", "A multicenter, investigator-blinded, randomized comparison of oral levofloxacin and oral clarithromycin in the treatment of acute bacterial sinusitis.", "Cefdinir versus levofloxacin in patients with acute rhinosinusitis of presumed bacterial etiology: a multicenter, randomized, double-blind study.", "Efficacy and safety of cefdinir in the treatment of maxillary sinusitis.", "[Amoxycillin-clavulanic acid and cefuroxime axetil in the treatment of acute sinusitis. A clinical, radiological and bacteriological evaluation].", "A multicenter, randomized, investigator-blinded study of 5- and 10-day gatifloxacin versus 10-day amoxicillin/clavulanate in patients with acute bacterial sinusitis.", "[Treatment of acute sinusal processes of adults with tetracycline and a combination of sulfamethopyrazine-trimethoprim].", "Loracarbef versus doxycycline in the treatment of acute bacterial maxillary sinusitis. Scandinavian Study Group.", "A comparison of the efficacy, tolerability and safety of azithromycin and co-amoxiclav in the treatment of sinusitis in adults.", "[Efficiency of a four-day course of pristinamycin compared to a five-day course of cefuroxime axetil for acute bacterial maxillary sinusitis in adult outpatients].", "Primary-care-based randomised placebo-controlled trial of antibiotic treatment in acute maxillary sinusitis.", "Are antibiotics beneficial for patients with sinusitis complaints? A randomized double-blind clinical trial.", "Clinical efficacy and time to symptom resolution of 5-day telithromycin versus 10-day amoxicillin-clavulanate in the treatment of acute bacterial sinusitis.", "Comparison of the efficacy and safety of faropenem daloxate and cefuroxime axetil for the treatment of acute bacterial maxillary sinusitis in adults.", "Comparative effectiveness and safety of cefdinir and amoxicillin-clavulanate in treatment of acute community-acquired bacterial sinusitis. Cefdinir Sinusitis Study Group.", "Efficacy and safety of a novel, single-dose azithromycin microsphere formulation versus 10 days of levofloxacin for the treatment of acute bacterial sinusitis in adults.", "Multicenter comparison of clarithromycin and amoxicillin in the treatment of acute maxillary sinusitis.", "An open comparative study of azithromycin versus cefaclor in the treatment of patients with upper respiratory tract infections.", "Efficacy of clarithromycin vs. amoxicillin/clavulanate in the treatment of acute maxillary sinusitis.", "Brodimoprim versus amoxicillin in the treatment of acute sinusitis." ]

[ "In an open randomized comparative study, the clinical and bacteriological efficacy and safety of spiramycin were compared with those of doxycycline in patients with acute sinusitis. Spiramycin was given at a dose of 1 g bd for 10 days and doxycycline at 200 mg once a day on day 1 and 100 mg once a day from day 2 to day 10. Clinical and bacteriological evaluations of efficacy were carried out at the end of therapy. In case of clinical cure, a last follow-up visit was made 15 days after the end of therapy. Adverse effects were recorded. To date 12 assessable patients have been treated with spiramycin and 15 with doxycycline. In the spiramycin group, nine patients were clinically cured at the end of therapy (with no relapse at the last follow-up visit). In the doxycycline group, nine patients were clinically cured at the end of therapy (with no relapse at the last follow-up visit). The data so far available from this study suggest that spiramycin presents an alternative to doxycycline in the treatment of acute sinusitis.", "This multicenter study compared the clinical and bacteriologic efficacy of two oral antibiotics, cefuroxime axetil and amoxicillin/clavulanate, in the treatment of acute bacterial maxillary sinusitis.\n Three hundred seventeen patients with clinical and radiographic evidence of acute maxillary sinusitis were enrolled at nine centers and were randomly assigned to receive 10 days of treatment with cefuroxime axetil 250 mg twice daily (n = 157) or amoxicillin/clavulanate 500 mg three times daily (n = 160). Patients were assessed for both clinical and bacteriologic responses once during treatment (5 to 7 days) and twice after treatment (1 to 3 days and 4 weeks). Bacteriologic assessments were based on needle aspirates of the maxillary sinus obtained pretreatment and, when possible, at the first posttreatment visit.\n Organisms were isolated from the pretreatment sinus aspirates of 198 of 317 (62%) patients, with the primary isolates being Streptococcus pneumoniae (22%), Haemophilus spp. (17%), Staphylococcus aureus (13%), and Haemophilus influenzae (10%). A satisfactory clinical outcome (cure or improvement) was achieved in 85% (98 of 115) and 82% (102 of 124) of the clinically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.446). With respect to the eradication of the bacterial pathogens, a satisfactory outcome (cure or presumed cure) was obtained in 84% (31 of 37) and 87% (34 of 39) of bacteriologically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (p = 0.567). Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events (13% versus 3%, p = 0.001), particularly diarrhea (8% versus 1%, p = 0.001). Two patients in the cefuroxime axetil group and three patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events.\n Our results indicate that cefuroxime axetil twice a day is as effective as amoxicillin/clavulanate three times a day in the treatment of acute bacterial maxillary sinusitis but produces fewer adverse effects.", "To compare the efficacy and tolerability of clarithromycin extended-release (ER) to amoxicillin/ clavulanate in patients diagnosed with acute bacterial sinusitis.\n In a controlled, multicenter, investigator-blinded study, 437 ambulatory patients at least 12 years old with signs/symptoms and radiographic findings of acute sinusitis were randomized to receive clarithromycin ER 1000 mg once daily or amoxicillin/ clavulanate 875 mg/l25 mg twice daily for 14 days.\n Clinical and bacteriological response rates were determined at a test-of-cure visit, which was conducted up to 10 days following the completion of treatment. Radiological response was assessed at a follow-up visit.\n The clinical cure rate in clinically evaluable patients was 98% (184/188) in the clarithromycin ER group and 97% (179/185) in the amoxicillin/clavulanate group (95% CI for the difference in rates [-2.4%, 4.7%]). Clinical cure was sustained at the follow-up visit (96% for each treatment group). The pathogen eradication rates were 94% (61/65) in the clarithromycin ER group and 98% (61/62) in the amoxicillin/clavulanate group (95% CI for difference in rates [-12.0%, 2.9%]). The radiological success rate was 94% (172/183) in both the clarithromycin ER and amoxicillin/clavulanate groups (95% CI for difference in rates [-4.9%, 4.9%]). Symptomatic improvement or relief was observed as early as 2 days-5 days after the initiation of study drug, with a statistically significantly higher resolution rate of sinus pressure (p = 0.027) and improvement/resolution rate of nasal congestion (p = 0.035) during treatment with clarithromycin ER. The resolution/improvement rate at the test-of-cure visit for each treatment group was > or = 94% for the primary acute sinusitis signs/symptoms, with a statistically significantly higher resolution/improvement rate of purulent nasal discharge with clarithromycin ER (p = 0.010). Both study drugs had a positive and rapid impact on quality of life. Patients reported a high level of satisfaction and probability of using either study antibiotic again, and health care resource use was low, with slightly fewer sinusitis-related physician and outpatient visits required by patients in the clarithromycin ER group (p = 0.055). The treatment groups were comparable with respect to incidence of drug-related adverse events.\n In this multinational population of patients with acute bacterial sinusitis, clarithromycin ER was comparable, and for selected measures superior, to amoxicillin/clavulanate based on clinical, bacteriological, and radiological responses as well as quality of life measures, satisfaction with antibiotic therapy, and health care resource utilization.", "To compare efficacy and tolerability of brodimoprim tablets with doxycycline tablets in adults with acute sinusitis.\n Open, randomized, controlled phase III study, with parallel groups.\n Of the 70 enrolled patients, 56 adults of both sexes with a mean age of 33 years were evaluable. STUDY DRUGS: One brodimoprim 200mg tablet or one doxycycline 100mg tablet was administered once daily for 8 to 12 days (on the first treatment day all patients received the loading dose consisting of 2 tablets of the corresponding compound).\n In the brodimoprim group 96.4% of the patients were judged cured/improved; in the doxycycline group 96.2%. BACTERIOLOGICAL OUTCOME: Eradication of the causative pathogen/s was achieved in 87.5% of the patients treated with brodimoprim and in 60% of the doxycycline group. SAFETY OUTCOME: Tolerability was judged as very good/good in 89.7% of the patients treated with brodimoprim and in all patients receiving doxycycline. Gastrointestinal skin, CNS and various other reactions were reported by 13 patients; 3 of them had to discontinue treatment. Discontinuation of therapy: 8 more patients withdrew from the study due to inactivity of the compound or reasons unrelated to the drugs.\n Brodimoprim was shown to be effective in the treatment of acute sinusitis in adults, its efficacy being equal to that of doxycycline. The assessments showed a positive clinical response to the medication in 96.4% of the patients treated with brodimoprim and 96.2% of the patients taking doxycycline. Both compounds were well tolerated and all side effects were of mild nature and reversible.", "The aim of this prospective, multicenter, randomized, double-masked clinical trial was to compare the efficacy and safety of moxifloxacin with those of cefuroxime axetil for the treatment of community-acquired acute sinusitis. Five hundred forty-two adult patients with symptoms and radiographic evidence of acute maxillary sinusitis received a 10-day oral regimen of either moxifloxacin (400 mg once daily) or cefuroxime axetil (250 mg twice daily). Acute signs and symptoms at presentation had lasted >7 days but <4 weeks. Clinical response at the end of therapy (7 to 14 days after treatment) was the primary efficacy variable. Four hundred fifty-seven of the patients (223 moxifloxacin, 234 cefuroxime axetil) were included in the clinical efficacy analysis. Moxifloxacin was found to be similar in effectiveness to cefuroxime axetil at the end-of-therapy visit (90% vs. 89%, respectively; 95% confidence interval, -5.1% to 6.2%). Clinical relapse at the follow-up visit was reported for only 8 patients (3 moxifloxacin, 5 cefuroxime axetil). No clinically significant differences were observed with respect to the number of patients experiencing a successful clinical response based on demographic or infection characteristics. Five of the 542 enrolled patients were lost to follow-up. Of the 537 patients in the intent-to-treat population, drug-related adverse events were reported in 37% of moxifloxacin-treated patients and in 26% of cefuroxime axetil-treated patients (P = 0.006). Adverse-event profiles were comparable in the 2 treatment groups, with the exception of nausea, which was reported by 11% of moxifloxacin-treated patients compared with 4% of cef uroxime axetil-treated patients (P = 0.003). In this study, moxifloxacin was as effective as cefuroxime axetil in the treatment of community-acquired acute sinusitis.", "To compare the clinical and bacteriologic efficacy and safety of short-duration treatment with telithromycin given for 5 days with moxifloxacin given for 10 days in adults with acute bacterial rhinosinusitis (ABRS).\n In this prospective, double-blind, parallel-group, randomized, multicenter study, adult patients (N = 349) with ABRS were randomized to oral telithromycin (800 mg once daily for 5 days) or to oral moxifloxacin (400 mg once daily for 10 days) and followed for 31 to 36 days. Clinical outcome was determined by the investigator at the posttherapy/test of cure (TOC) visit. Bacteriologic outcome was determined by comparing cultures taken at the pretreatment visit with cultures obtained at the posttherapy/TOC visit. The primary objective was to demonstrate equivalence of clinical cure rates in the per-protocol population between treatment groups at the posttherapy/TOC visit.\n Clinical success at TOC (primary endpoint) was achieved in 87.4% of patients in the telithromycin group compared with 86.9% for moxifloxacin (per-protocol patients; 0.5% difference between treatment groups; 95% confidence interval [CI], -8.1, 9.2; P = 0.8930). The bacteriologic success rates were 94.1% and 93.9%, respectively (0.2% difference between treatment groups; 95% CI, -14.2, 14.5; P = 0.9734). Overall treatment-emergent adverse events for both drugs (mostly gastrointestinal) were mild to moderate in intensity.\n The clinical and bacteriologic efficacy of telithromycin 800 mg once daily for 5 days was equivalent to that of moxifloxacin 400 mg once daily for 10 days, establishing telithromycin as an important treatment option for ABRS.", "The aim of this study was to compare the efficacy and safety of moxifloxacin with that of amoxicillin/clavulanate for the treatment of acute bacterial sinusitis in adults.\n Five hundred seventy-five patients from Latin American countries were randomized to receive oral moxifloxacin 400 mg once daily for 7 days, or oral amoxicillin/clavulanate 500/125 mg 3 times daily for 10 days, in a prospective, open study.\n At the test-of-cure visit (7-14 days after the end of therapy), the clinical success rate in the moxifloxacin group was 93.4% similar to that in the amoxicillin/clavulanate group (92.7%). Documented bacteriological eradication plus presumed eradication rates in the moxifloxacin (96.5%) and the amoxicillin/clavulanate (96.7%) groups were also similar. Drug-related adverse events were recorded in 32.2% of patients in the moxifloxacin group and 29.7% in the amoxicillin/clavulanate group. Patient discontinuation in the trial due to adverse events occurred for 10 patients in the moxifloxacin group and 6 in the amoxicillin/clavulanate group.\n Overall, in terms of clinical and bacteriological response, moxifloxacin was equivalent to amoxicillin/clavulanate for the treatment of acute bacterial sinusitis in adults.", "The efficacy and safety of minocycline were compared with that of amoxicillin in the treatment of 58 patients with acute bacterial sinusitis. The most frequently isolated pathogens were streptococci, staphylococci, and Haemophilus influenzae. After therapy for a mean time of 11 days, clinical cure or improvement and bacterial eradication were evident in 100% of the patients treated with minocycline and in 95% of the patients treated with amoxicillin. Roentgenographic results indicated clearing or improvement in 91% of the minocycline recipients and in 70% of those who received amoxicillin. These differences between treatments were not statistically significant. A low incidence of generally mild adverse clinical experiences occurred in both treatment groups. Thus, minocycline and amoxicillin were equally safe and effective in the treatment of these patients with acute bacterial sinusitis.", "The efficacy and safety of clarithromycin and amoxycillin in the treatment of acute maxillary sinusitis were compared in a single-blind, multicentre outpatient study. Fifty patients were randomly assigned to receive either clarithromycin 500 mg 12-hourly or amoxycillin 500 mg 8-hourly orally. Clinical signs and symptoms, sinus culture and blood and urine laboratory profiles were assessed prior to treatment, at four to six days during treatment, and within 48 h of the end of therapy (usually 9-11 days). Patients from whom beta-lactamase producing strains were isolated were excluded from the study. Both antibiotics achieved a clinical success rate of 91% within 48 h post-treatment; radiological resolution or improvement was observed in 91% of patients treated with clarithromycin and 89% of patients who received amoxycillin. Bacteriological cure was achieved in 88% and 91% of evaluable patients for clarithromycin and amoxycillin, respectively. Adverse events were reported for 16% of patients in the clarithromycin group compared to 26% in the amoxycillin group. Gastrointestinal disturbance was the most commonly occurring adverse event in both groups. The results of this study suggest that clarithromycin is as effective and well tolerated as amoxycillin in the treatment of acute maxillary sinusitis.", "Adult patients with acute sinusitis (n = 236) were randomized in a double-blind study to levofloxacin 500 mg orally once daily (n = 119) or clarithromycin 500 mg orally twice daily (n = 117) for 10-14 days. Between 2 and 5 days after therapy participants were evaluated as cured (no symptoms), improved (symptoms improved, no further therapy required), or failed (further therapy required). Clinical response rates (cured plus improved) for clinically evaluable patients were 93.9% for levofloxacin (n = 98) and 93.5% for clarithromycin (n = 93). The proportion of patients evaluated as cured was higher in the levofloxacin (40.8%) than in the clarithromycin arm (29.0%) and individual symptoms showed higher rates of resolution. Of patients receiving levofloxacin and clarithromycin, 22.5% and 39.3%, respectively, experienced adverse events related or possibly related to the study therapy. This study showed that, in the treatment of acute sinusitis, daily levofloxacin therapy is as effective as twice-daily clarithromycin therapy with more complete clearing of symptoms and a more tolerable side-effect profile.", "To compare the efficacy and safety of faropenem medoxomil, 300 mg twice daily for seven or ten days, with cefuroxime axetil 250 mg twice daily for ten days in adults with acute bacterial sinusitis (ABS).\n Prospective, double-blinded, phase III trial with entry criteria consistent with FDA/IDSA guidelines for diagnosis of ABS. Primary efficacy parameter was clinical response at 7 to 21 days posttherapy.\n One thousand ninety-nine subjects were randomized and treated; 861 were efficacy valid. Clinical cure rates were 80.3% for seven days of faropenem, 81.8% for ten days of faropenem, and 74.5% for 10 days of cefuroxime axetil. The incidence of adverse events and premature discontinuations were similar for the three treatment regimens.\n Seven- and ten-day faropenem medoxomil regimens were similar (noninferior) to a ten-day cefuroxime axetil regimen based on clinical response in patients with ABS.\n A seven-day course of faropenem medoxomil 300 mg twice-daily regimen is a promising alternative for treatment of ABS.", "The treatment of acute, recurrent, and chronic sinusitis remains controversial because of the presence of a wide variety of aerobic and anaerobic bacteria in the sinuses.\n This double-blind, randomized trial compared cefaclor with amoxicillin in the treatment of acute, recurrent, and chronic maxillary sinusitis using clinical evaluation, roentgenography, and microbiologic evaluation of antral aspirates.\n Outpatient office of five otorhinolaryngologists in Salt Lake City, Utah.\n One hundred eight adult patients with acute, recurrent, or chronic maxillary sinusitis.\n Oral treatment with cefaclor (500 mg) twice daily or amoxicillin (500 mg) three times daily for 10 days.\n Clinical response to treatment with cefaclor vs amoxicillin.\n Fifty-six patients with acute sinusitis, 25 with recurrent sinusitis, and 15 with chronic sinusitis were evaluable. Although multiple organisms were common in each group, patients with acute sinusitis were more likely to have Haemophilus influenzae or Streptococcus pneumoniae, and patients with recurrent or chronic sinusitis were more likely to have anaerobes in sinus aspirate. Whether treated with cefaclor or amoxicillin, clinical improvement occurred in 86% of patients with acute sinusitis and 56% of patients with recurrent sinusitis. Patients with chronic sinusitis were too few to allow statistical analysis of the differences in outcome between them and patients with recurrent or acute sinusitis. Resistance of the cultured organisms to the study drug used was unrelated to treatment outcome.\n The rate of clinical improvement was high in patients with acute sinusitis but was less favorable in those with recurrent and chronic disease regardless of the study drug used. The susceptibility of organisms isolated to the study drugs was unrelated to outcome.", "The objective of the study was to compare the clinical efficacy and bacteriological response of levofloxacin and amoxicillin/clavulanic acid (co-amoxiclav) in the treatment of purulent maxillary sinusitis. Sixty patients randomly received either levofloxacin 300 mg orally once daily (LEV group) or co-amoxiclav 625 mg three times a day (COA group) for 14 days. Thirty four patients were in the LEV group and 26 patients were in the COA group. The mean total symptom score was significantly decreased after treatment and was comparable between both groups. Radiological improvement was 61.8% in the LEV group (41.2% resolution, 20.6% improvement) and 61.5% in the COA group (26.9% resolution, 34.6% improvement). Pretreatment maxillary antral aspiration cultures were positive in 28 patients (82.4%) in the LEV group and 20 patients (76.9%) in the COA group. Bacteriological eradication was 78.5% in the LEV group and 70.0% in the COA group, which was not significantly different. In the LEV group, the eradication rate for major pathogens of acute sinusitis was 100% for H. influenzae (both betalactamase +ve and -ve), 100% for S. pneumoniae and S. aureus, 100% for Neisseria species, and 66.7% for P. aeruginosa. The eradication rate in the COA group was 75% for H. influenzae (both betalactamase +ve and -ve), 100% for S. pnumoniae and S. aureus, 50% for Neisseria species, and 0% for P. aeruginosa. There were no significant changes in vital sign measurements or hemato-biochemical parameters at the end of treatment as compared to baseline values, in both groups. Adverse events were found in 8.8% of patient in the LEV group and in 7.7% of patients in the COA group. Adverse events included nausea, abdominal pain, and diarrhea. All the adverse events in both groups were mild and resolved spontaneously. This study demonstrated that levofloxacin 300 mg orally once daily was as effective and safe as amoxicillin/clavulanic acid 625 mg three times a day in the treatment of maxillary sinusitis, either acute or acute exacerbation. Both drugs showed bacteriological efficacy that was not significantly different. The once daily dosage regimen is more applicable, convenience and has better compliance.", "In this comparative trial, outpatients with acute sinusitis were randomly assigned to receive levofloxacin (500 mg orally once daily) or amoxicillin-clavulanate (500/125 mg orally 3 times daily) for 10 to 14 days. The success rates (cured and improved) 2 to 5 days after the end of treatment were 88.4% for the 267 clinically evaluable patients who received levofloxacin and 87.3% for the 268 clinically evaluable patients who received amoxicillin-clavulanate. Drug-related adverse events occurred in a smaller percentage of patients in the levofloxacin treatment group (7.4%) than in the amoxicillin-clavulanate treatment group (21.2%). The most common of these were nausea, diarrhea, vaginitis, and abdominal pain for levofloxacin-treated patients and diarrhea, vaginitis, nausea, genital moniliasis, abdominal pain, vomiting, and flatulence for amoxicillin-clavulanate-treated patients. The results of this study show that once-daily administration of levofloxacin is as effective and better tolerated than amoxicillin-clavulanate administered 3 times daily for treating acute sinusitis in adult outpatients.", "We compared the efficacy of penicillin V and amoxycillin treatment with placebo in 70 adult patients from Norwegian family practice with a clinical diagnosis of acute sinusitis and mucosal thickening on CT, but without fluid level or total opacification. The study was randomized and double-blind. Three different outcomes were evaluated; subjective status after 10 days of treatment, difference in clinical score between day 0 and day 10, and duration of the illness episode. Amoxycillin and penicillin V gave no better response to treatment than placebo, evaluated by all three outcome measures. The median duration of the sinusitis episode was 10 days in the amoxycillin- and placebo groups and 13 days in the penicillin-V group. In patients with a clinical diagnosis of acute sinusitis, fluid level and total opacification on CT are good criteria to differentiate between groups of patients that need or do not need antibiotic treatment.", "The efficacy and tolerability of ceftibuten 400 mg o.d. or 200 mg b.i.d. was compared with amoxicillin/clavulanate (AMX/CA, 500 mg/125 mg) t.i.d. in the treatment of acute sinusitis. This was a multicenter, open, randomized, parallel-group 8-day study. In total, 450 patients were evaluable for safety and 400 patients for efficacy. At day 10, clinical cure rates were 83% in the ceftibuten 400 mg o.d. group, 87% in the ceftibuten 200 mg b.i.d. group and 89% in the AMX/CA t.i.d. group; the clinical/radiological cure rates were 52, 44 and 56%, respectively. Clinical and clinical/radiological cure rates at day 40 for the ceftibuten 400 mg o.d. group, ceftibuten 200 mg b.i.d. group and the AMX/CA t.i.d. group were similar, with clinical cure rates of 81, 82 and 87%, and clinical/radiological cure rates of 62, 58 and 63%, respectively. Most adverse events were mild. Ceftibuten, 400 mg o.d. or 200 mg b.i.d., was equally effective and well tolerated as AMX/CA t.i.d. in the treatment of acute sinusitis.", "The aim of the study was to compare early symptom resolution with a single 2-g dose of azithromycin extended release or 10 days of amoxicillin/clavulanate 875 mg/125 mg every 12 hours in patients with acute sinusitis.\n This was a prospective, randomized, open-label, observational study to mimic \"real-world\" conditions, including patients with symptoms of acute bacterial sinusitis lasting between 7 and 30 days. Key symptoms were assessed twice daily by patient diary, and patients were interviewed by telephone at 12 and 28 days. The primary end point was symptom resolution at 5 days, defined as reporting \"no problem\" with at least 3 of 4 diary symptoms in 2 consecutive measures in the per-protocol population. Secondary end points included additional antibiotic use, sinusitis-related quality of life, and treatment satisfaction.\n Three hundred seventy-eight patients were randomized to a single dose of azithromycin extended release and 371 to 10 days of amoxicillin/clavulanate. In the per-protocol population at day 5, 70/236 patients (29.7%) in the azithromycin extended release arm and 45/238 patients (18.9%) in the amoxicillin/clavulanate arm had resolution of symptoms (difference = 10.8%; 95% confidence interval [CI], 3.1-18.4%). By day 28, 26/236 patients (11.0%) in the azithromycin extended release arm and 27/238 patients (11.3%) in the amoxicillin/clavulanate arm had used additional antibiotics (difference = -0.4%; 95% CI: -6.1% to 5.3%). Additional physician visits, quality of life, and overall satisfaction were similar between groups.\n More patients randomized to azithromycin extended release experienced symptom resolution at day 5 than those randomized to amoxicillin/clavulanate, without experiencing differences in second antibiotic use at 28 days.", "Loracarbef (LY 163892), a beta-lactam antibiotic (carbacephem), was compared with amoxicillin/clavulanate potassium in a 10-day, single-blind, randomized parallel trial in the treatment of acute bacterial maxillary sinusitis. Based on posttherapy aspirate and culture, there was a 95.2% bacteriologic cure rate in patients receiving loracarbef (400 mg twice daily) and an 86.7% cure rate in patients receiving amoxicillin/clavulanate (500/125 mg three times daily) (p = 0.359). Loracarbef was comparable in efficacy to amoxicillin/clavulanate with a more desirable safety profile.", "nan", "In this double-blind, parallel-group, multicenter study, 169 patients with symptoms of maxillary sinusitis but without radiographically confirmed empyema (pus) were randomly assigned to receive either 500 mg azithromycin once daily for 3 days (87 patients) or placebo daily for 3 days (82 patients). Nasal secretion, maxillary tenderness and pain, nasal obstruction, general malaise, and hyposmia were assessed at the start of the study and on days 4, 11, and 25 of treatment. After 11 days 58% of the patients in the azithromycin group were cured versus 31% in the placebo group; after 25 days the cure rate was 79% versus 67%, respectively. When both cure and improvement were considered, the corresponding figures after day 25 were 90% and 88%, respectively. Adverse events, predominantly gastrointestinal, occurred in 24 (27%) of the azithromycin-treated patients and in 15 (18%) of those treated with placebo, but the difference was not statistically significant. There was a difference in efficacy in favor of azithromycin in the treatment of rhinitis with symptoms of maxillary sinusitis but without radiological signs of empyema (pus). Antibiotics should only be used to alleviate symptoms in patients with moderate to severe symptoms, as the results after 25 days for both improvement and cure are equal. In the treatment of acute rhinitis with symptoms and signs of maxillary sinusitis but without empyema, treatment with azithromycin seems to result in a better cure rate after 10-12 days when compared with placebo.", "The aim of this multicentre, randomized study was to compare the efficacy and safety of moxifloxacin (BAY 12-8039), a new 8-methoxy fluoroquinolone, with that of cefuroxime axetil for the treatment of acute bacterial sinusitis in adults. Diagnosis was made on a range of clinical signs and symptoms combined with radiology and microbiology. A 400 mg dose of moxifloxacin was administered once daily for 7 days to 242 patients and 250 mg twice daily of cefuroxime axetil was administered to 251 patients for 10 days. The clinical success rate at the end of treatment in the evaluable population was significantly higher (96.7%) in the moxifloxacin group (204/211) than in the cefuroxime axetil group (204/225, 90.7%; 95% confidence intervals 1.5%; 10.6%). At follow-up the success rate in the moxifloxacin group was 90.7% and that for the cefuroxime axetil group was 89.2% (95% confidence intervals -4.3%; 5.4%). The predominant pathogens isolated were Streptococcus pneumoniae and Haemophilus influenzae, followed by Moraxella catarrhalis and Staphylococcus aureus. The bacteriological eradication rates were higher for moxifloxacin (94.5%, 103/109) than for cefuroxime axetil (83.5%, 96/115; 95% CI 3.6%; 19.7%). Only one S. pneumoniae infection persisted following moxifloxacin therapy in contrast with three in individuals on cefuroxime axetil. There were slightly more adverse events in the moxifloxacin group than in the cefuroxime axetil group, but there were fewer serious adverse events following moxifloxacin treatment (three vs. eight). The drug was discontinued because of adverse events in 14 moxifloxacin patients and in 11 cefuroxime axetil patients. Overall, in all assessments, moxifloxacin was at least as effective clinically and bacteriologically, and as well tolerated, as cefuroxime axetil in the treatment of acute sinusitis.", "In a double-blind, multicentre trial, 382 patients with a diagnosis of acute purulent sinusitis were randomised to receive sparfloxacin 200 mg once daily for 5 days following a loading dose of 400 mg on day 1 (n = 193) or cefuroxime axetil 250 mg twice daily for 8 days (n = 189). Patients were classified as success or failure according to clinical symptoms plus bacteriological and radiological data at the end of treatment and at a follow-up visit. In analyses of the intent-to-treat (n = 374) and evaluable populations (n = 304), the 5 day course of sparfloxacin was at least as effective and well tolerated as the 8 day course of cefuroxime axetil. The success rates at the end of treatment in the evaluable population were 82.6% and 83.2% in the sparfloxacin and cefuroxime axetil groups, respectively. The pathogens isolated most frequently were Haemophilus influenzae (33%) and Streptococcus pneumoniae (28%). Response rates according to the bacterial aetiology of the acute sinusitis were similar in the two treatment groups. Both drugs were well tolerated. The commonest adverse events were gastrointestinal and were reported in 2.6% and 3.8% of sparfloxacin- and cefuroxime axetil-treated patients, respectively.", "The efficacy and safety of clarithromycin and amoxicillin-clavulanate in the treatment of acute maxillary sinusitis was compared in an open multicenter outpatient study. Two hundred and eighty patients were randomly assigned to receive either clarithromycin 500 mg 12-hourly or amoxicillin-clavulanate 500 mg 8-hourly orally for 8 days. Clinical and radiologic signs and symptoms, and sinus culture were not significantly different in the two treatment groups. A clinical and radiological success or improvement was achieved after the end of treatment in 115/134 (85.8%) patients treated with clarithromycin and in 110/129 (85.3%) patients treated with amoxicillin-clavulanate. Adverse events were reported for 14.8% and 12.2% of patients for clarithromycin and amoxicillin-clavulanate, respectively. In this study clarithromycin was as effective and well tolerated as amoxicillin-clavulanate acid in the treatment of acute maxillary sinusitis.", "In the treatment of acute maxillary sinusitis, azithromycin offers an advantage over phenoxymethylpenicillin in that a complete course of treatment requires drug administration once daily for only three days. In this double-blind, parallel-group, multicenter study, 438 patients with radiographically verified maxillary sinusitis were randomly assigned to receive either 500 mg azithromycin once daily for three days (221 patients) or 1.3 g phenoxymethylpenicillin three times daily for ten days (217 patients). Nasal secretion, maxillary tenderness and pain, nasal obstruction, general malaise, and hyposmia, were assessed at the start of the study and on days 4, 11, and 25 of treatment. After 11 days 58% of the patients in the azithromycin group were cured versus 51% in the penicillin group; after 25 days the cure rate was 79% versus 76%, respectively. When both cure and improvement were considered, the corresponding figures after 11 days were 97% (azithromycin) and 95% (penicillin); after 25 days they were 92% and 88%, respectively. Adverse events, predominantly gastrointestinal, occurred in 73 (33%) of the azithromycin-treated patients and in 87 (40.1%) of those treated with penicillin. No difference in efficacy was found between the two drugs in the treatment of acute maxillary sinusitis, and the adverse effects were comparable. The short duration of treatment with azithromycin offers a significant advantage over treatment with phenoxymethylpenicillin.", "Telithromycin, a new ketolide, exhibits potent activity against respiratory pathogens, including resistant strains.\n Five days of telithromycin (800 mg once daily) was compared with 10 days of cefuroxime axetil (250 mg twice daily) in subjects (n = 593) with acute bacterial maxillary sinusitis (ABMS). Bacteriologic sampling was accomplished by sinus puncture or nasal endoscopy. The primary efficacy variable was clinical outcome at the posttherapy/test-of-cure evaluation in clinically evaluable patients.\n Clinical cure was achieved in 85.2% of telithromycin patients and 82.0% of cefuroxime axetil patients (difference in proportions, 3.2%; 95% confidence interval, -7.1-13.4%). Satisfactory bacteriologic response rates were comparable. Treatment-emergent adverse events for both drugs were mild or moderate. The most frequently reported treatment-emergent adverse events were nausea and diarrhea.\n Once-daily telithromycin for 5 days was equivalent in efficacy to twice-daily cefuroxime axetil for 10 days in patients with ABMS. Telithromycin is a suitable option for short-course therapy of ABMS.", "This multicenter, randomized, double-blind trial compared the efficacy and safety of ciprofloxacin (CIP; 500 mg twice daily for 10 days, placebo for 4 days) to those of clarithromycin (CLARI; 500 mg twice daily for 14 days) in 560 adults with clinically documented and radiologically confirmed acute sinusitis. Of 457 efficacy-valid adults (236 CIP, 221 CLARI), clinical resolution plus improvement at the end of therapy was 84% for CIP-treated patients compared to 91% of CLARI recipients (CI95 = -0.131, -0.013). At the 1-month follow-up, more than twice as many CLARI-treated patients, 18 (10%), experienced a relapse, compared to 7 (4%) CIP-treated patients. The combined clinical response analyses (end of therapy and 1 -month follow-up) demonstrated that CIP and CLARI were statistically equivalent (CI95 = -0.106, 0.044). Diarrhea, nausea, headache, and dizziness were the most frequently reported drug-related adverse events in both treatment groups; diarrhea and taste perversion were reported more frequently among CLARI recipients. In summary, the combined end of therapy and follow-up clinical evaluation analyses revealed that CIP and CLARI were equally effective in the management of acute sinusitis, although twice as many relapses were reported among CLARI recipients.", "Telithromycin (HMR 3647) is a new ketolide antimicrobial that was developed for the treatment of community-acquired respiratory tract injections. We conducted a randomized, double-blind, multicenter study to compare the clinical efficacy and safety of oral telithromycin, at 800 mg once daily for 5 or 10 days, with that of amoxicillin/clavulanic acid, at 500/125 mg three times daily for 10 days, in adults with acute maxillary sinusitis (AMS). A total of 754 patients with AMS of less than 28 days' duration were randomized to receive either telithromycin for 5 days followed by placebo for 5 days, telithromycin for 10 days, or amoxicillin/clavulanic acid for 10 days. Clinical outcome was assessed at a test-of-cure (TOC) visit between days 17 and 24 and at a late post-therapy visit between days 31 and 45. Analysis of clinical outcome on a per-protocol basis (n = 434) demonstrated therapeutic equivalence among the three regimens at the TOC visit; in each treatment group, the clinical cure rate was approximately 75%. Only a few patients (3 to 5 in each group) had relapsed by the late post-therapy follow-up visit. Telithromycin was generally safe and well tolerated. The most common adverse events were mild or moderate gastrointestinal effects, which occurred with similar frequency in all three groups. We conclude that 5 or 10 days of telithromycin at 800 mg once daily is as effective clinically and as well tolerated as 10 days of treatment with amoxicillin/clavulanic acid. Telithromycin, therefore, appears to be a valuable option for the treatment of AMS.", "To compare the effectiveness of penicillin V and amoxycillin with placebo in treatment of adult patients with acute sinusitis.\n Randomised, double blind, placebo controlled trial.\n Norwegian general practice.\n 130 adult patients with a clinical diagnosis of acute sinusitis confirmed by computed tomography.\n Subjective status after three and 10 days of treatment, difference in clinical severity score between day 0 and day 10 as evaluated by the general practitioner, difference in score from computed tomography on day 0 and day 10, and duration of sinusitis.\n Amoxycillin and penicillin V led to significantly faster and better recovery than placebo. By day 10, 71 patients receiving antibiotic treatment- (86%) considered themselves to be recovered or much better compared with 25 (57%) receiving placebo. The mean (95% confidence interval) reductions in clinical severity scores by day 10 were 5.4 (5.0 to 5.8) for penicillin V, 5.5 (4.9 to 6.0 for amoxycillin, and 3.4 (2.8 to 4.0) for placebo. For the antibiotic groups combined the number of patients with the greatest degree of improvement on computed tomography (scale 0-16)-that is, score 5-16 on day 10-was 31/83 (37%) compared with 10/44 (23%) receiving placebo. The median duration of the sinusitis was nine days in the amoxycillin group, 11 days in the penicillin V group, and 17 days in the placebo group.\n Penicillin V and amoxycillin are significantly more effective than placebo in the treatment of acute sinusitis.", "In order to evaluate the clinical efficacy and tolerance of cefpodoxime proxetil, compared with that of amoxicillin in the treatment of acute bacterial maxillary sinusitis, a randomized, double-blind, parallel group comparative study was performed. A total of 286 adults patients were included at 12 centres, each treatment group consisting of 143 patients. Each patient was treated for 10 days and observed before and after treatment. The observations included clinical, roentgenological, bacteriological and laboratory examinations. At inclusion, the most common pathogens were Haemophilus influenzae (24%) and Streptococcus pneumoniae (17%). In the per protocol analysis, 117 patients in the cefpodoxime group and 113 in the amoxicillin group were evaluable for clinical efficacy. The clinical response rates were 96% and 91%, respectively. The corresponding figures in the intent-to-treat analysis were 130 and 128 patients, with clinical response rates of 93% and 88%, respectively. Cefpodoxime proxetil proved clinically as effective as amoxicillin in the treatment of acute bacterial maxillary sinusitis. It was more effective in eradicating H. influenzae and was more efficient in improving the radiological score. Adverse events were reported in 20% of cefpodoxime cases and in 16% of amoxicillin cases. There was no statistically significant difference between the groups.", "In an open, randomized study of 60 patients with acute or recurrent sinusitis, the bacteriological and clinical efficacy of roxithromycin 150 mg bd were compared with those of po co-amoxiclav (625 mg) tds. Of 52 patients who underwent sinus puncture for isolation of causative organisms, 48 had pathogens sensitive to both antibiotics. Satisfactory clinical response was obtained in 93.1% (27/29) evaluable patients receiving roxithromycin and 88.8% (24/27) receiving co-amoxiclav. Tolerability was significantly better in the roxithromycin group, with 1/29 (3.4%) patients in this group experiencing gastrointestinal side-effects, compared with 7/27 (25.9%) patients in the co-amoxiclav group (P < 0.05). Although the study had limited power to detect differences, roxithromycin demonstrated clinical, bacteriological and overall efficacy similar to that of co-amoxiclav, but with better tolerability. Roxithromycin thus appears to be an effective and well-tolerated drug for the treatment of acute and recurrent sinusitis.", "Acute maxillary sinusitis is a common condition requiring broad-spectrum therapy to prevent development of chronic disease. A randomised, double-blind, multicentre study was performed to compare the efficacy and safety of cefuroxime axetil 250 mg twice daily (n = 185) and clarithromycin 250 mg twice daily (n = 185), both administered for 10 days, in the treatment of patients with acute sinusitis. Efficacy was determined by assessment of clinical response at post-treatment and follow-up, and by radiological assessment at pre-treatment and follow-up. Assessment of days absent from work due to illness was also made. In the cefuroxime axetil group, 169/185 (91%) patients were cured/improved at post-treatment, as were 172/185 (93%) patients receiving clarithromycin and, of these, 137/169 (81%) and 143/172 (83%) maintained their response at follow-up. Follow-up radiography showed a reduction in incidence of air fluid level and/or opacification from 96% to 15% (cefuroxime axetil) and from 96% to 11% (clarithromycin), and a decrease in frequency of mucosal thickening from 58% to 28% (cefuroxime axetil) and from 56% to 29% (clarithromycin). Only 10% of patients in either group experienced adverse events and days absent from work were comparable. This study demonstrated clinical equivalence between twice-daily cefuroxime axetil and clarithromycin, both treatments being effective and well tolerated.", "A randomized, double-blind, multicenter study of adults with acute bacterial sinusitis (ABS) compared the efficacy and safety of two azithromycin (AZM) regimens, 500 mg/day once daily for 3 days (AZM-3) or 6 days (AZM-6) to the efficacy and safety of an amoxicillin-clavulanate (AMC) regimen of 500-125 mg three times daily for 10 days. A total of 936 subjects with clinically and radiologically documented ABS were treated (AZM-3, 312; AZM-6, 311; AMC, 313). Clinical success rates were equivalent among per-protocol subjects at the end of therapy (AZM-3, 88.8%; AZM-6, 89.3%; AMC, 84.9%) and at the end of the study (AZM-3, 71.7%; AZM-6, 73.4%; AMC, 71.3%). Subjects treated with AMC reported a higher incidence of treatment-related adverse events (AE) (51.1%) than AZM-3 (31.1%, P < 0.001) or AZM-6 (37.6%, P < 0.001). More AMC subjects discontinued the study (n = 28) than AZM-3 (n = 7) and AZM-6 (n = 11) subjects. Diarrhea was the most frequent treatment-related AE. AZM-3 and AZM-6 were each equivalent in efficacy and better tolerated than AMC for ABS.", "In this prospective, multicentre, randomised, non-blinded phase III clinical trial, 475 adult patients with acute sinusitis received a 10-day oral regimen of either moxifloxacin (400 mg once daily) or amoxicillin clavulanate (875 mg twice daily). The primary measure of efficacy was clinical resolution. Secondary outcome measures included clinical relapse at follow-up and evaluation of patient reported outcomes. Of 471 adults comprising the intent-to-treat population (234 moxifloxacin, 237 amoxicillin/clavulanate), moxifloxacin treatment was statistically equivalent to amoxicillin/clavulanate at the test-of-cure visit (85% vs 82%; 95% CI -6%, 13%). Analysis of the efficacy evaluable population, confirmed statistical equivalence (86% vs 84%; 95% CI -7%, 13%). Of note, by day 3 of treatment, significantly more moxifloxacin-treated patients (n = 47; 24%), than amoxicillin/clavulanate-treated patients (n = 28; 14%), reported feeling better (p < 0.02). Frequency of drug-related adverse events were similar between groups: nausea (11% moxifloxacin, 5% amoxicillin/clavulanate) and diarrhoea (3% moxifloxacin, 10% amoxicillin clavulanate). In conclusion, once-daily moxifloxacin is as effective and safe as twice-daily amoxicillin/clavulanate in the treatment of acute sinusitis. Moxifloxacin is associated with more rapid symptomatic relief.", "To compare the efficacy and tolerability of a 3-day course of azithromycin with a 10-day course of amoxicillin/clavulanic acid in the treatment of acute sinusitis in adults.\n One hundred adult patients with acute sinusitis were included in an open, randomized study. Clinical diagnosis of sinusitis was confirmed by nasal endoscopy, sinus radiography, and (when possible) by culture of sinus aspirate. Patients were randomized to receive azithromycin (500 mg once daily for 3 days) or amoxicillin/clavulanate (625 mg every 8 hours for 10 days).\n A significantly faster resolution of signs and symptoms of sinusitis was observed in the azithromycin-treated patients. By the end of therapy (days 10-12), 95% of the patients in the azithromycin group and 74% in the amoxicillin/clavulanate group were cured. The remaining patients' conditions were improved. By the follow-up visit, cure was achieved in 98% of the azithromycin-treated patients, and 91% of the amoxicillin/clavulanate-treated patients. Treatment failure was observed in three patients from the amoxicillin/clavulanate group, and relapse occurred in one patient from each group. Bacteriologic eradication was achieved in 23 of 23 and 21 of 24 patients treated with azithromycin and amoxicillin/clavulanate, respectively. Both drugs were well tolerated. Two patients (4%) from the azithromycin group and five patients (10%) from the amoxicillin/clavulanate group reported mild gastrointestinal disturbances.\n In adults with acute sinusitis, a 3-day course of azithromycin was as effective and well tolerated as a 10-day course of amoxicillin/clavulanic acid. A significantly simpler dosage regimen and faster clinical effect were the advantages of azithromycin.", "Cefprozil is a beta-lactamase-stable oral cephalosporin with an antimicrobial spectrum that includes gram-positive and gram-negative pathogens commonly associated with acute bacterial sinusitis, one of the most common upper respiratory tract infections among adults. We conducted a multicenter, open-label study to compare the efficacy and safety of cefprozil and amoxicillin/clavulanate in the treatment of adults with severe acute bacterial sinusitis diagnosed by clinical and radiographic criteria. A total of 278 patients entered the study, 140 (59 males, 81 females) in the cefprozil group and 138 (69 males, 69 females) in the amoxicillin/clavulanate group. Patients were randomized to 10 days of treatment with either cefprozil 500 mg BID or amoxicillin/clavulanate 500 mg/125 mg TID. Clinical severity was assessed at study entry, and patients were stratified based on symptom grade. Efficacy was evaluated using a 10-point questionnaire administered during, at the end of, and 2 weeks after completing therapy. At the end of treatment, 84.5% (71/84) of patients with severe sinusitis treated with cefprozil had a satisfactory clinical response, which was not significantly different from the 89.9% (80/89) of patients in the amoxicillin/clavulanate group who had a satisfactory clinical response. Two weeks after completing treatment, 80.8% (63/78) of cefprozil-treated patients and 81.0% (64/79) of amoxicillin/clavulanate-treated patients with severe sinusitis had a satisfactory response. Relapse was more common among amoxicillin/clavulanate patients (6/70; 8.6%) than among cefprozil patients (2/65; 3.1%), but the difference was not statistically significant. Significantly more amoxicillin/clavulanate-treated patients experienced adverse events compared with cefprozil-treated patients (P < 0.001), including diarrhea (P < 0.001), nausea (P < 0.042), and rash (P < 0.035). Three times as many amoxicillin/clavulanate patients discontinued treatment because of adverse events. Cefprozil demonstrated comparable clinical efficacy to amoxicillin/clavulanate in the treatment of adults with severe sinusitis; however, cefprozil was associated with a significantly lower incidence of diarrhea, nausea, and rash.", "A multicenter, investigator-blinded, randomized, parallel-group study was conducted to compare oral levofloxacin 500 mg once/day for 14 days with clarithromycin 500 mg twice/day for 14 days in the treatment of acute bacterial sinusitis. Of 216 adult outpatients randomized to treatment, 190 were evaluable for efficacy. The primary efficacy measure was clinical response, based on resolution of signs and symptoms 2-5 days after therapy. A secondary efficacy measure was relapse rate 1 month after therapy. Among evaluable patients, clinical success rates (cured or improved) were 96.0% and 93.3% for levofloxacin (L) and clarithromycin (C), respectively (95% CI -9.2%, 3.7%). The confidence interval (CI) for treatment difference (C-L) included zero and its upper limit was less than 15%, indicating that levofloxacin was as effective as clarithromycin. In all, 4.1% of patients receiving levofloxacin and 7.2% receiving clarithromycin had a relapse of symptoms 1 month after therapy (95% CI-12.2%, 3.2%). Long-term success (initial success, absence of relapse at 1 month, no further antibacterial therapy 2-5 days after therapy) was 79.2% in the levofloxacin group and 76.4% in the clarithromycin group (95% CI -14.7%, 9.0%). Based on investigator-assessed treatment-emergent adverse events, overall tolerability of the drugs was similar, except for a higher frequency of taste perversion and diarrhea in the clarithromycin group. Levofloxacin had an advantage over clarithromycin based on two quality-of-life (QOL) parameters: number of times taking other drugs for targeted medical conditions and mean total cost of these drugs. No statistical significance was found in other QOL variables. These findings suggest that the efficacy and tolerability of levofloxacin 500 mg once/day are comparable with those of clarithromycin 500 mg twice/day in the treatment of acute bacterial sinusitis.", "Treatment guidelines for acute bacterial rhinosinusitis (ABRS) recommend 10 to 14 days of therapy with high-dose amoxicillin, amoxicillin/clavulanate, cefdinir, cefpodoxime, cefuroxime, a macrolide, or a newer fluoroquinolone, among other agents.\n This study compared the clinical efficacy and tolerability of cefdinir and levofloxacin in patients with a diagnosis of acute rhinosinusitis of presumed bacterial origin.\n In this multicenter, double-blind, noninferiority study, ambulatory adult patients who had signs and symptoms for >7 to 21 days before the screening visit and radiographic findings consistent with acute rhinosinusitis were randomized to receive cefdinir 600 mg or levofloxacin 500 mg, each once daily for 10 days. Clinical and radiologic response rates were determined at the test-of-cure (TOC) visit, which took place 9 to 14 days after the completion of treatment.\n Two hundred seventy-one patients (138 cefdinir, 133 levofloxacin) were enrolled and randomized to treatment at 27 study centers in the United States and Poland between November 2003 and March 2004. Of these, 241 (123 cefdinir, 118 levofloxacin) were clinically evaluable. The cefdinir group consisted of 75 women and 48 men, of whom 117 were white and 6 black; their mean (SD) age was 42.5 (14.3) years. The levofloxacin group consisted of 71 women and 47 men, of whom 111 were white and 7 black; their mean age was 40.4 (13.6) years. The 2 groups were similar in terms of presenting signs and symptoms and baseline radiographic findings. The most common presenting symptoms were sinus pain, sinus pressure, and purulent nasal discharge, each of which was reported by > or =89% of patients. Clinical cure rates at the TOC visit in the cefdinir and levofloxacin groups were 83% (102/123) and 86% (101/118), respectively (95% Cl for the difference in cure rates, -12.3 to 7.0). Cefdinir and levofloxacin were comparable in the treatment of infections classified as moderate to severe. The incidence of drug-related adverse events was generally comparable in the 2 treatment groups, although there were significant differences between cefdinir and levofloxacin in the incidence of vaginal moniliasis in women (11% vs 0%, respectively; P = 0.003), drug-related diarrhea (8% vs 1%; P = 0.005), and insomnia (0% vs 4%; P = 0.027). Only 2% of patients discontinued therapy prematurely as a result of a drug-related adverse event.\n In this population of patients with ABRS, the extended-spectrum cephalosporin cefdinir was as efficacious as the fluoroquinolone levofloxacin, suggesting that cefdinir may be a suitable alternative to the currently recommended fluoroquinolones.", "Cefdinir is a new, extended-spectrum, orally active, third-generation cephalosporin that is resistant to bacterial beta-lactamase production. To evaluate efficacy and safety of the antibiotic in maxillary sinusitis, its use was compared with amoxicillin/clavulanate (amox/clav), which is a well-accepted beta-lactamase-resistant antibiotic. In this investigator-blinded multicenter phase III clinical study, 569 patients were randomly assigned to one of three treatment regimens: one daily dose of cefdinir 600 mg (OD), cefdinir 300 mg every 12 h (BD), and amox/clav 500/125 mg every 8 h. All antibiotics were administered orally for 10 days. Maxillary sinusitis was documented by typical clinical signs and symptoms and was confirmed by X-ray imaging. Before treatment, the genus and species of any pathogens were determined from sinus aspirates. Cultures were tested for beta-lactmase production and in vitro resistance to cefdinir and amox/clav. The effectiveness of antibiotic treatment was evaluated 7-14 days after therapy and whether or not recurrent clinical symptoms or persistent infection was determined 21-35 days post-therapy. The appearance of any adverse events was classified as associated or not associated with the medication of the study. Present findings showed that the in vitro susceptibility of pathogens to cefdinir and amox/clav was similar. Cefdinir OD or BD was therapeutically as effective as or better than amox/clav, although cefdinir BD was not as useful as amox/clav clinically. Cefdinir OD and BD and amox/clav were well tolerated. The statistical incidence of adverse events was the same among the three treatment groups, although cefdinir OD treatment had significantly fewer treatment discontinuations due to adverse events than BD and amox/clav.", "Cefuroxime axetil (CAE), an orally absorbed product of cefuroxime, and amoxycillin/clavulanate (AAC), were evaluated for their efficacy and safety in the treatment of acute sinusitis. A total of 47 patients were enrolled in a randomized study to compare cefuroxime axetil 500 mg. b.d. for 8 days (25 patients) with amoxycillin/clavulanate 500 mg. t.d.s for 8 days (22 patients). All patients were evaluable for clinical, radiological and bacteriological response. Of 25 clinically assessable patients treated with CAE, 24 were cured, 1 improved and 1 relapsed (96% success rate). Of 22 assessable patients given AAC, 14 were cured and 8 improved (100% success rate). Two out of 25 (8%) patients treated with CAE experienced drug-related adverse events, including 4% with diarrhoea. In the AAC group, 3 out of 22 (13%) patients had a drug-related adverse event, including 13% with diarrhoea. In conclusion, CAE appears to be as safe and effective as AAC in the treatment of acute sinusitis.", "Treatment guidelines for acute bacterial sinusitis recommend 10 to 14 days of therapy with amoxicillin/clavulanate, high-dose amoxicillin, cefpodoxime, cefuroxime, or a newer fluoroquinolone. Objective: This study compared the clinical efficacy of short-course (5-day) gatifloxacin with standard 10-day regimens of amoxicillin/clavulanate or gatifloxacin in patients with a diagnosis of acute, uncomplicated maxillary sinusitis.\n This was a multicenter, investigator-blinded study in adult patients (age >18 years) with physical findings, signs and symptoms (for at least 7 days), and radiographic findings indicating acute, uncomplicated maxillary sinusitis. Patients were randomized to receive gatifloxacin 400 mg once daily for 5 days, gatifloxacin 400 mg once daily for 10 days, or amoxicillin/clavulanate 875 mg twice daily for 10 days. Clinical response was assessed once between days 3 and 5 of treatment, once I to 3 days after the completion of study treatment, once 7 to 14 days posttreatment (test-of-cure visit), and once 21 to 28 days posttreatment. Safety was assessed throughout the study.\n The study enrolled 445 patients. The treatment groups were similar in terms of history of sinusitis, presenting signs and symptoms, and radiographic findings. The most common presenting symptoms were nasal congestion, sinus tenderness, and purulent nasal discharge (>90% of patients); 99% of patients had abnormal radiographic findings. At the test-of-cure visit, clinical cure rates for clinically evaluable patients in the 3 treatment groups were 74% (102/137) for 5-day gatifloxacin, 80% (101/127) for 10-day gatifloxacin, and 72% (101/ 141) for 10-day amoxicillin/clavulanate (95% CI for the difference in cure rates: 5-day gatifloxacin vs amoxicillin/clavulanate, -7.6 to 13.2; 5- vs 10-day gatifloxacin, -15.2 to 5.1; 10-day gatifloxacin vs amoxicillin/clavulanate, -2.3 to 18.1). The distribution and incidence of drug-related adverse events (AEs) were comparable between treatment groups, and the majority (>95%) were mild or moderate in severity. The most common drug-related AEs included vaginitis, diarrhea, and nausea.\n In this population of patients with acute, uncomplicated sinusitis of presumed bacterial origin, a short course (5 days) of gatifloxacin therapy was associated with comparable clinical cure rates and tolerability to those of standard 10-day therapy with gatifloxacin or amoxicillin/clavulanate.", "nan", "In a double-blind, multicentre study, 662 patients with acute maxillary sinusitis were randomly assigned to receive either loracarbef 400 mg bd (332 patients) or doxycycline, 200 mg for the first dose followed by 100 mg od, (330 patients) for ten days. One hundred and sixty-eight patients in the loracarbef group and 164 in the doxycycline group were evaluable for efficacy. Streptococcus pneumoniae and/or Haemophilus influenzae were isolated from approximately 75% of patients. The clinical response rate (cure or improvement) was significantly higher for patients receiving loracarbef (98.2%) than for those who received doxycycline (92.2%). There was no significant difference between the two groups with respect to bacteriological outcome, although more of the pre-treatment isolates were resistant to doxycycline (35 strains) than to loracarbef (five strains). Adverse events related to the gastrointestinal tract occurred in 11.7% and 10.6% of loracarbef- and doxycycline-treated patients respectively; therapy was terminated prematurely in ten patients in the loracarbef group and in nine in the doxycycline group. The results indicate that loracarbef is effective and safe treatment for acute maxillary sinusitis.", "The efficacy, tolerability and safety of azithromycin and co-amoxiclav in the treatment of non-severe acute maxillary/ethmoidal sinusitis were compared in a randomized, open clinical trial in 254 adult patients. The predominant pathogens were Streptococcus pneumoniae and Haemophilus influenzae (83 patients). Azithromycin was administered orally to 165 patients at a single daily dose of 500 mg for 3 days, and co-amoxiclav (4:1) to 89 patients, at a dose of 500 mg three times daily for 10 days. The overall clinical response rates were 87.5% for azithromycin and 83.7% for co-amoxiclav at follow-up (day 21-28). Microbiological responses to both drugs were good, with only five patients in each group having a persistent infection after treatment. Both drugs were well tolerated and produced similar incidences of adverse events, which were mostly gastrointestinal. Azithromycin was as effective, and as well tolerated as co-amoxiclav, and its shorter simpler dosing regime may offer advantages in compliance and cost.", "The aim of this multicentric, randomized, double blind study was to demonstrate that a 4-day treatment with pristinamycin 1 g bid was as efficient as a 5-day treatment with cefuroxime axetil 250 mg bid in adults presenting with an acute maxillary sinusitis.\n The clinical diagnosis was based on the association of sub-orbital pain, purulent rhinorrhea and purulent discharge on the middle nasal meatus and was confirmed radiologically. A rhinoscopic bacteriologic sampling was made on the middle nasal meatus.\n Four hundred and eighty five patients were included in the study: in France (n = 301), Tunisia (n = 48), Poland (n = 69) and Argentina (n = 67) between January 2001 and February 2002. Cultures were positive in 199/434 patients (46%), mainly S. pneumoniae (34.2%), H. influenzae (21.5%), S. aureus (15.4%), and M. catharralis (7.9%). The clinical cure rate at day 12-19 in the per protocol population, the main study criterion, was equal to 91.4% (201/220) and 91.1% (195/214) respectively in the pristinamycin and cefuroxime axetil groups; delta = 0.14%; 95%CI: [-5.1%; 5.3%]. The non-inferiority of 4-day pristinamycin versus 5-day cefuroxime axetil was demonstrated. The efficacy at follow up after treatment (day 26-31) was 88.6% and 85.8% respectively, confirming the non-inferiority. The bacteriological cure rate at day 12-19 was 87% (87/100) and 87.9% (87/99) respectively. Both treatments were well tolerated.\n A 4-day course with pristinamycin 1 g bid is as effective as a 5-day course of cefuroxime axetil 250 mg bid in the treatment of acute maxillary sinusitis in adults.", "The value of antibiotics in acute rhinosinusitis is uncertain. Although maxillary sinusitis is commonly diagnosed and treated in general practice, no effectiveness studies have been done on unselected primary-care patients. We used a randomised, placebo-controlled design to test the hypothesis that there would be an improvement associated with amoxycillin treatment for acute maxillary sinusitis patients presenting to general practice.\n Adult patients with suspected acute maxillary sinusitis were referred by general practitioners for radiographs of the maxillary sinus. Those with radiographic abnormalities (n = 214) were randomly assigned treatment with amoxycillin (750 mg three times daily for 7 days; n = 108) or placebo (n = 106). Clinical course was assessed after 1 week and 2 weeks, and reported relapses and complications were recorded during the following year.\n After 2 weeks, symptoms had improved substantially or disappeared in 83% of patients in the study group and 77% of patients taking placebo. Amoxycillin did not influence the clinical course of maxillary sinusitis nor the frequency of relapses during the 1-year follow-up. Radiographs had no prognostic value, nor were they an effect modifier. Side-effects were recorded in 28% of patients given amoxycillin and in 9% of those taking placebo (p < 0.01). The occurrence of relapses was similar in both groups (21 vs 17%) during the follow-up year.\n Antibiotic treatment did not improve the clinical course of acute maxillary sinusitis presenting to general practice. For these patients, an initial radiographic examination is not necessary and initial management can be limited to symptomatic treatment. Whether antibiotics are necessary in more severe cases warrants further study.", "Sinusitis is the fifth most common reason for patients to visit primary care physicians, yet clinical outcomes relevant to patients are seldom studied.\n To determine whether patients with purulent rhinitis, \"sinusitis-type symptoms,\" improved with antibiotics. Second, to examine a clinical prediction rule to provide preliminary validation data.\n Prospective clinical trial, with double-blinded placebo controlled randomization. The setting was a suburb of Washington, DC, from Oct 1, 2001, to March 31, 2003. All participants were 18 years or older, presenting to a family practice clinic with a complaint of sinusitis and with pus in the nasal cavity, facial pressure, or nasal discharge lasting longer than 7 days. The main outcome measures were resolution of symptoms within a 14-day follow-up period and the time to improvement (days).\n After exclusion criteria, 135 patients were randomized to either placebo (n=68) or amoxicillin (n=67) for 10 days. Intention-to-treat analyses showed that 32 (48%) of the amoxicillin group vs 25 (37%) of the placebo group (P=.26) showed complete improvement by the end of the 2-week follow-up period (relative risk=1.3; 95% confidence interval [CI], 0.87-1.94]). Although the rates of improvement were not statistically significantly different at the end of 2 weeks, the amoxicillin group improved significantly earlier, in the course of treatment, a median of 8 vs 12 days, than did the placebo group (P=.039).\n For most patients with sinusitis-type complaints, no improvement was seen with anti-biotics over placebo. For those who did improve, data suggested there is a subgroup of patients who may benefit from antibiotics.", "This study compared the clinical efficacy, time to symptom resolution, and tolerability of a 5-day regimen of telithromycin with a 10-day regimen of high-dose amoxicillin-clavulanate in acute bacterial sinusitis (ABS).\n In this multinational (41 centers in Canada, Germany, Greece, Portugal, and Turkey), open-label, noninferiority study, patients >/=18 years old (n=298) with a clinical (>7 days' symptoms) and radiological (air/fluid level, total opacification, mucosal thickening >/=10 mm) diagnosis of ABS were randomized to receive telithromycin 800 mg once daily for 5 days or amoxicillin-clavulanate 875/125 mg twice daily for 10 days. Clinical efficacy and tolerability were assessed at the test-of-cure visit (days 17-21). Time to symptom resolution was based on patients' daily diary assessment of individual symptoms.\n The per-protocol clinical success rate (primary endpoint) with telithromycin (88.6% (109/123)) was noninferior to that with amoxicillin-clavulanate (88.8% (111/125)) (95% confidence interval: -8.9 to 8.5). In the modified intention-to-treat (mITT) population, the median time for 50% reduction of total symptom scores was significantly shorter for telithromycin (4 days) vs. amoxicillin-clavulanate (5 days; p=0.044); median times for 75% reduction of total symptom scores were: telithromycin, 7 days; amoxicillin-clavulanate, 8 days (p=0.115). The median time for reduction of total symptom scores to the absent/very mild category (mITT population) was 6 days for telithromycin vs. 8 days for amoxicillin-clavulanate (p=0.04). All treatment-emergent adverse events (TEAEs) were mostly gastrointestinal and occurred in 20.7% (30/145) of telithromycin-treated patients vs. 31.8% (47/148) of amoxicillin-clavulanate-treated patients (p=0.034). One serious AE was reported in the telithromycin group, but it was considered not to be related to treatment.\n This open-label, randomized study demonstrated that treatment of ABS with telithromycin resulted in comparable clinical efficacy, shorter times to symptom resolution, and fewer total TEAEs than treatment with amoxicillin-clavulanate.", "In this multicentre, multinational, comparative, double-blind clinical trial, outpatients with both clinical signs and symptoms and radiographic evidence of acute sinusitis were randomly assigned to receive for 7 days either a twice-daily oral regimen of faropenem daloxate (300 mg) or a twice daily oral regimen of cefuroxime axetil (250 mg). Among 452 patients considered valid for clinical efficacy, faropenem daloxate treatment was found to be statistically equivalent to cefuroxime axetil (89.0% vs. 88.4%-95% CI=-5.2%; +6.4%) at the 7-16 days post-therapy assessment. At 28-35 days post-therapy, the continued clinical cure rate in the faropenem daloxate group was 92.6% and that for the cefuroxime axetil group was 94.9% (95% CI: -6.8%; +1.2%). A total of 148 organisms was obtained in 136 microbiologically valid patients (30.1%). The predominant causative organisms were Streptococcus pneumoniae (47.1%), Haemophilus influenzae (30.1%), Staphylococcus aureus (14.7%) and Moraxella catarrhalis (8.8%). The bacteriological success rate at the 7-16 days post-therapy evaluation was similar in both treatment groups: 91.5% and 90.8% in the faropenem daloxate and cefuroxime axetil groups, respectively (95% CI=-9.2%; +9.5%). Eradication or presumed eradication was detected for 97.3% and 96.3% of S. pneumoniae, 85.0% and 90.5% of H. influenzae, 88.9% and 90.9% of S. aureus and 100.0% and 83.3% of M. catarrhalis in faropenem daloxate and cefuroxime axetil recipients, respectively. At least one drug-related event was reported by 9.5% of the faropenem daloxate-treated patients and by 10.3% of those who received cefuroxime axetil. The most frequently reported drug-related events were diarrhoea (2.2% versus 2.9%), nausea/vomiting (1.5% vs. 0.7%), abdominal pain (0.7% vs 1.5%) and skin reactions (1.5% vs. 1.1%). Overall, faropenem daloxate was at least as effective clinically and bacteriologically as cefuroxime axetil and was well tolerated.", "Cefdinir is an extended-spectrum oral cephalosporin that is active against pathogens commonly seen in acute community-acquired bacterial sinusitis (ACABS), including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Two randomized, investigator-blind, multicenter trials (one in the United States and one in Europe) compared two dosage regimens of cefdinir (600 mg once a day for 10 days and 300 mg twice a day for 10 days) to amoxicillin-clavulanate (A-C) (500 mg three times a day for 10 days) for adult and adolescent patients with ACABS. Twelve hundred twenty-nine patients entered the U.S. study, 698 with antral puncture; 569 patients entered the European study, all with antral puncture. Clinical response (cure or improvement) was determined 7 to 14 days and 3 to 5 weeks posttherapy. Microbiologic eradication rates were determined 10 to 30 days posttherapy in a subset of patients who underwent pre- and posttherapy sinus aspirate culture. Rates of adverse events and treatment discontinuations due to adverse events were examined. Cefdinir, given once or twice daily, was as effective clinically (approximately 90% cure rate) as amoxicillin-clavulanate given three times daily in the treatment of ACABS. Microbiologic eradication rates were also similar in the three groups. The major side effect was mild diarrhea, occurring in approximately 20% of each group. Cefdinir caused fewer adverse events requiring treatment discontinuation.", "To compare the efficacy and safety of a single 2.0-g dose of a novel azithromycin microsphere formulation with that of 10 days of levofloxacin, 500 mg/d, when used to treat adults with uncomplicated acute bacterial maxillary sinusitis (ABS).\n An international, multicenter, randomized, double-blind, double-dummy trial. Eligible outpatients > or =18 years of age with clinical and radiographic evidence of ABS underwent maxillary sinus aspiration before randomization. Primary endpoint was clinical efficacy at the test-of-cure visit (day 17-24).\n Clinical success rates were 94.5% (242/256) in azithromycin-microspheres-treated patients and 92.8% (233/251) in the levofloxacin group. In patients with documented Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, clinical cure rates were 97.3% (36/37), 96.3% (26/27), and 100% (8/8), respectively, for the azithromycin group and 92.3% (36/39), 100% (30/30), and 90.9% (10/11), respectively, for the levofloxacin group.\n Single-dose azithromycin microspheres provided clinical and bacteriologic efficacy and safety comparable to 10 days of levofloxacin.\n A novel microsphere formulation of azithromycin given as a single dose was safe and effective for the treatment of ABS.", "To compare the safety and efficacy of orally administered clarithromycin, a new macrolide antimicrobial, and amoxicillin in the treatment of patients with acute maxillary sinusitis.\n One hundred forty-two consecutive outpatients treated at four primary care centers for acute maxillary sinusitis were randomly assigned to receive oral clarithromycin (500 mg twice daily) or oral amoxicillin (500 mg three times daily) for 7 to 14 days. Clinical and roentgenographic responses to the antibiotic therapy were determined within 48 hours after the last dose and 6 weeks later.\n The success rates of clarithromycin and amoxicillin were comparable. A clinical success rate of 91% and a roentgenographic success rate of 78% were achieved in the clarithromycin group at the final visit; comparable results for the amoxicillin group were 89% and 92%, respectively. Differences between the two groups were not statistically significant (P = .766 and .064, respectively). No serious adverse events were reported, although both drugs caused mild gastrointestinal distress. Dropout rates were low in both groups: 3% for clarithromycin and 4% for amoxicillin. No clinically significant changes in laboratory studies were observed in either group.\n Clarithromycin twice daily is effective and well tolerated in patients with acute maxillary sinusitis.", "Azithromycin and cefaclor were compared for the treatment of acute otitis media, streptococcal pharyngitis/tonsillitis, or sinusitis in an open multicentre study conducted in 530 adults. At the end of therapy (day 11-15), 228/245 (93%) patients treated with azithromycin 500 mg once daily for 3 days and 233/241 (97%) treated with cefaclor 250 mg given three times daily for 10 days were considered to have responded satisfactorily (cured or improved). In bacteriologically evaluable patients with pharyngitis/ tonsillitis, Streptococcus pyogenes was eradicated in 116/117 (99%) azithromycin- and in 115/119 (97%) cefaclor-treated patients at day 11-15; one patient in each group had become reinfected after initial eradication of the pathogen. When followed up on day 25-30, S. pyogenes infection had recurred in 5/105 (5%) azithromycin and 4/108 (3%) cefaclor patients who had responded satisfactorily at day 11-15, and whose baseline pathogen had been eradicated. Of these patients, two in the azithromycin and one in the cefaclor group also relapsed clinically; the others remained asymptomatic. Patients tolerated both treatments well; treatment-related adverse events were recorded in 11% of the 267 azithromycin- and 10% of the 263 cefaclor-treated patients assessed for safety. One azithromycin patient and five cefaclor patients withdrew because of adverse events. The results of the study show that a 3-day regimen of azithromycin, given once daily, is as effective and well tolerated as a multiple-daily, 10-day cefaclor regimen for the treatment of upper respiratory tract infections in adults.", "A new macrolide drug, clarithromycin (Biaxin) was compared with amoxicillin/clavulanate (Augmentin) in a single-blind (investigator-blind), randomized, multicenter study of 497 outpatients with acute maxillary sinusitis; treatment was 500 mg clarithromycin bid (n = 246) or 500 mg amoxicillin/clavulanate tid (n = 251). Pathogens included Streptococcus pneumoniae in 22% of patients, Staphylococcus aureus in 16%, Haemophilus influenzae in 10%, and Moraxella catarrhalis in 7%. For evaluable patients, clinical success (cure or improvement) was noted for 97% (128/132) of clarithromycin recipients and 93% (119/128) amoxicillin/clavulanate recipients. Clinically significant improvement in signs and symptoms was comparable between groups. Bacteriologic cure rates were 87% (115/132) and 90% (115/128), respectively. Respective pathogen eradication rates were 87% (125/143) and 90% (125/139). Adverse events not due to concurrent conditions occurred in 41% of the former and 46% of the latter group; most were mild to moderate gastrointestinal upsets (21% and 38%, respectively; P < 0.001). We conclude that clarithromycin appears to be as effective as amoxicillin/clavulanate in acute maxillary sinusitis and may cause fewer gastrointestinal upsets.", "A new dihydrofolate inhibitor, brodimoprim, was compared with amoxicillin in the treatment of acute sinusitis in a general practice controlled study. Eighty adult outpatients with acute sinusitis were randomly assigned to receive 200 mg of brodimoprim once daily or 750 mg of amoxicillin thrice daily for seven to 10 days. The mean duration of treatment was 9.2 days in the brodimoprim group and 9.1 days in the amoxicillin group. In most patients the symptoms of sinusitis had disappeared by day 5 of treatment. The reduction in symptom scores was more marked in the brodimoprim-treated patients than in the amoxicillin-treated patients. Bacteriologic examinations after treatment were performed in 20 patients of each treatment group. At completion of treatment, the causative pathogen had been eradicated in 14 of 20 patients treated with brodimoprim and in 12 of 20 patients treated with amoxicillin. Treatment side effects were reported by two brodimoprim-treated patients (skin reactions) and by six amoxicillin-treated patients (gastrointestinal distrubances or skin reactions). The results indicate that brodimoprim is safe and effective in the treatment of acute sinusitis in adults." ]

[ "2512486", "17981885", "14531817", "2636680", "10511331", "17462550" ]

[ "The effect of protein restriction on the progression of renal insufficiency.", "Metabolic effects of two low protein diets in chronic kidney disease stage 4-5--a randomized controlled trial.", "Supplemented very low protein diet ameliorates responsiveness to erythropoietin in chronic renal failure.", "Protein-restricted diets in chronic renal failure: a four year follow-up shows limited indications.", "Effects of severe protein restriction with ketoanalogues in advanced renal failure.", "Effects of a supplemented hypoproteic diet in chronic kidney disease." ]

[ "Dietary protein intake may be an important determinant of the rate of decline in renal function in patients with chronic renal insufficiency. We conducted a prospective, randomized study of the efficacy of protein restriction in slowing the rate of progression of renal impairment. The study lasted 18 months and included 64 patients with serum creatinine concentrations ranging from 350 to 1000 micromol per liter. The patients were randomly assigned to follow either a regular diet or an isocaloric protein-restricted diet (0.4 g of protein per kilogram of the body weight per day). Blood-pressure levels and the balance between calcium and phosphate were similar in the two groups. End-stage renal failure developed in 9 of the 33 patients (27 percent) who followed the regular diet during the study, as compared with 2 of the 31 patients (6 percent) who followed the protein-restricted diet (P less than 0.05). The mean (+/- SE) glomerular filtration rate, as measured by the clearance of 51Cr bound to EDTA, fell from 0.25 +/- 0.03 to 0.10 +/- 0.05 ml per second (P less than 0.01) in the group on the regular diet, whereas it fell from 0.23 +/- 0.04 to 0.20 +/- 0.05 ml per second (P not significant) in the group on the protein-restricted diet. We conclude that dietary protein restriction is effective in slowing the rate of progression of chronic renal failure.", "International guidelines have not reached a complete agreement about the optimal amount of dietary proteins in chronic kidney disease(CKD). The aim of this study was to compare, with a randomized-controlled design, the metabolic effects of two diets with different protein content (0.55 vs 0.80 g/kg/day) in patients with CKD stages 4-5.\n Study design and sample size calculations were based on previously published experience of our group with low protein diet. The primary outcome of the study was the modification of serum urea nitrogen concentration. From 423 patients randomly assigned to the two diets 392 were analysed: 200 for the 0.55-Group and 192 for the 0.8-Group. The follow-up ranged 6-18 months.\n Mean age was 61+/-18 years, 44% were women, mean eGFR was 18+/-7 ml/min/month. Three months after the dietary assignment and throughout the study period the two groups had a significantly different protein intake (0.72 vs 0.92 g/kg/day). The intention-to-treat analysis did not show any difference between the two groups. Compliance to the two test diets was significantly different (P < 0.05): 27% in the 0.55-Group and 53% in the 0.8-Group, with male gender and protein content (0.8 g/kg/day) predicting adherence to the assigned diet. The per protocol analysis, conversely, showed that serum urea nitrogen, similar at the time of randomization, significantly increased in the 0.8-Group vs 0.55-Group by 15% (P < 0.05). Serum phosphate, PTH and bicarbonate resulted similar in the two groups throughout the study. The 24 h urinary urea nitrogen significantly decreased after the first 3 months in 0.55-Group (P < 0.05), as well as the excretion of creatinine, sodium and phosphate (P < 0.05 vs baseline) and were significantly lower than the 0.8-Group. The prescription of phosphate binders, allopurinol, bicarbonate supplements and diuretics resulted significantly less frequent in the 0.55-Group (P < 0.05).\n This study represents the first evidence that in CKD patients a protein intake of 0.55 g/kg/day, compared with a 0.8 g/kg/day, guarantees a better metabolic control and a reduced need of drugs, without a substantial risk of malnutrition.", "The aim of this study was to evaluate the relationship between uremic state and erythropoiesis in patients with predialytic chronic renal failure (CRF).\n We monitored for 2 years the erythropoietin (EPO) requirement in patients with advanced CRF (creatinine clearance < or =25 mL/min), randomized to either low protein diet (LPD) group (0.6 g/kg body weight/day, N = 10) or very low protein diet (VLPD) group (0.3 g/kg body weight/day, N = 10) supplemented with a mixture of ketoanalogs and essential amino acids, both kept at target hemoglobin levels.\n The achieved protein intake after 6 months was 0.79 +/- 0.02 g/kg body weight/day and 0.50 +/- 0.02 g/kg body weight/day in LPD and VLPD, respectively; such a difference was maintained up to the end of follow up. The final hemoglobin values did not differ from the basal values in either group (11.5 +/- 0.2 g/dL and 11.5 +/- 0.3 g/dL). EPO dose, that was similar at baseline (62.4 +/- 9.6 UI/kg body weight/week and 61.8 +/- 8.8 UI/kg body weight/week subcutaneously), remained unchanged in LPD but progressively decreased in VLPD down to the final value of 41.2 +/- 7.0 UI/kg body weight/week (P < 0.0001 vs. basal and LPD). VLPD was associated with a decrease of urinary excretion and serum levels of urea nitrogen and phosphate; however, EPO requirement was not correlated with the changes of these parameters. On the contrary, the variation of EPO dose directly correlated with the modification of parathyroid hormone (PTH) levels, that diminished from 229 +/- 55 pg/mL to 118 +/- 16 pg/mL (P < 0.0001) in VLPD and did not change in LPD.\n In patients with advanced CRF, an effective decrease of protein intake of 0.3 g/kg body weight/day induces a reduction of about 35% of the EPO dose required to maintain the target hemoglobin levels. This effect appears dependent on the correction of a moderate secondary hyperparathyroidism.", "Several retrospective and prospective studies confirmed the beneficial effect of dietary protein restriction (DPR) on the downhill course of renal function in chronic kidney disease. The long-term results of this therapeutic modality may be different than the short-term effects. In our nephrology outpatient department, a prospective randomized trial has been in progress since April, 1982. In 1984, we reported a general beneficial effect of our diet after two years of follow-up. Two hundred and forty-eight patients with initial creatinine clearances between 10 and 60 ml/min entered the trial. Patients were stratified for sex, age and degree of renal insufficiency. One hundred and twenty-nine patients were randomly assigned to a DPR-group (0.4 to 0.6 g/kg/day); 118 patients to a control group. Patients on DPR visited the dietitian every three months during the first 24 months of the study; thereafter, as with the controls, the dietitian visits were only for specific needs. Urea excretion decreased significantly in DPR patients as a sign of good compliance and stayed at that level, even without frequent visits to the dietitian. Biochemical parameters showed no signs of malnutrition. Amino acid profiles were related to the degree of renal failure. The diet appeared to have a selective effect on the progression rate of renal failure: only patients with primary glomerular disease responded to the diet. Furthermore, there were striking intersex differences. Males showed a more rapid decline towards end-stage renal failure, but responded in a positive way to the diet, whereas female patients did not benefit from the dietary manipulation at all.(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare a severe protein restriction diet supplemented with ketoanalogues to a moderate protein restriction diet in order to limit glomerular filtration rate (GFR) decrease in an advanced renal insufficiency stage.\n Prospective randomised study conducted to compare a severe protein restriction diet (0.30 g/kg/day) supplemented with a preparation of ketoanalogues, hydroxyanalogues of aminoacids and aminoacids (Group A) to a moderate protein restriction diet (0.65 g/kg/day) (Group B).\n 50 uremic patients included (25 in each group) with GFR is <20 mL/min/1.73m2.\n There were no statistically significant differences between the two dietary regimens for the renal survival. But uremia decreased significantly in Group A (22.7+/-5.2 to 18.5+/-6.7 mmol/L) and increased in Group B (26.8+/-9.0 to 34.9+/-9.9 mmol/L). Calcemia increased in Group A from 2.28+/-0.18 to 2.42+/-0.17 mmol/L, p<0.01 with a stable phosphoremia while calcemia decreased in Group B (2.33+/-0.18 to 2.25+/-0.17 mmol/L, p<0.05). At the end of the study, Group A was different from Group B for calcemia (2.42+/-0.17 vs. 2.25+/-0.17 mmol/L, p<0.01), phosphoremia (1.39+/-0.30 vs. 1.80+/-0.65 mmol/L, p<0.02), alkaline phosphatase (61.42+/-22.93 vs. 78.8+/-27.0, p<0.05) and parathormone plasma levels (2.71+/-1.55 vs. 5.91+/-1.41 ng/mL, p<0.001).\n Compared to a moderate protein restriction (0.65 g/kg/day), a severe protein restriction (0.3 g/kg/day) supplemented by ketoanologues does not limit GFR decrease when GFR is below 20 mL/min/1.73m2, but improves phosphocalcic plasma parameters.", "We assessed the effect of a severe hypoproteic diet supplemented with ketoanalogues (SVLPD) for 48 weeks on certain metabolic disorders of chronic kidney disease (CKD).\n We performed a prospective, open-label, parallel, randomized, controlled trial.\n The study took place in the Nephrology Department at the Dr Carol Davila Teaching Hospital of Nephrology, Bucharest, Romania.\n A total of 53 nondiabetic patients with CKD with an estimated glomerular filtration rate less than 30 mL/min/1.73 m(2) (Modification of Diet in Renal Disease formula), proteinuria less than 1 g/g urinary creatinine, good nutritional status, and anticipated good compliance with the diet were randomly assigned to two groups.\n Group I (n = 27) received the SVLPD (0.3 g/kg/d of vegetable proteins and ketoanalogues, 1 capsule for every 5 kg of ideal body weight per day). Group II (n = 26) continued a conventional low mixed protein diet (0.6 g/kg/d).\n Nitrogen waste products retention and calcium-phosphorus and acid-base disturbances were primary efficacy parameters, and \"death\" of the kidney or the patient and the estimated glomerular filtration rate were secondary efficacy parameters. The nutritional status and compliance with the diet were predefined as safety variables. There were no differences between groups in any parameter at baseline.\n In the SVLPD group, serum urea significantly decreased (56 +/- 7.9 mmol/L vs. 43.2 +/- 10 mmol/L), and significant improvements in serum bicarbonate (23.4 +/- 2.1 mmol/L vs. 18.1 +/- 1.5 mmol/L), serum calcium (1.10 +/- 0.17 mmol/L vs. 1.00 +/- 0.15 mmol/L at baseline), serum phosphates (1.45 +/- 0.66 mmol/L vs. 1.91 +/- 0.68 mmol/L), and calcium-phosphorus product (1.59 +/- 0.11 mmol(2)/L(2) vs. 1.91 +/- 0.10 mmol(2)/L(2)) were noted after 48 weeks. No death was registered in any group. Significantly lower percentages of patients in group I required renal replacement therapy initiation (4% vs. 27%). After 48 weeks, estimated glomerular filtration rate did not significantly change in patients receiving SVLPD (0.26 +/- 0.08 mL/s vs. 0.31 +/- 0.08 mL/s at baseline), but significantly decreased in controls (0.22 +/- 0.09 mL/s vs. 0.30 +/- 0.07 mL/s). The compliance with the keto-diet was good in enrolled patients. No significant changes in any of the parameters of the nutritional status and no adverse reactions were noted.\n SVLPD seems to ameliorate the nitrogen waste products retention and acid-base and calcium-phosphorus metabolism disturbances and to postpone the renal replacement therapy initiation, preserving the nutritional status in patients with CKD." ]

[ "6387105", "319967", "329324", "4591853", "4214658", "769023", "7046898", "4210459", "349428", "4606115", "6356386", "6349740", "13443", "7043498", "345313", "3902105", "1099598", "98196", "4932748", "4608709", "1112170", "7035441", "4699105", "2694767", "7093596", "329323", "7011468", "4214674", "4923721", "799401" ]

[ "The relationship of dopamine receptor blockade to clinical response in schizophrenic patients treated with pimozide or haloperidol.", "Pimozide versus fluphenazine in ambulatory schizophrenics: A 12-month comparison study.", "A standard- (trifluoperazine) controlled clinical study with pimozide in the maintenance treatment of schizophrenic patients, II.", "Pimozide (R6238) in chronic schizophrenia: double blind trial.", "A double-blind comparison of pimozide vs. trifluoperazine in schizophrenic outpatients.", "A three-year double-blind investigation of pimozide versus fluphenazine in chronic schizophrenia.", "Comparison of pimozide and chlorpromazine in acute schizophrenia.", "A double-blind comparison of once-a-day pimozide, trifluoperazine, and placebo in the maintenance care of chronic schizophrenic outpatients.", "The observer interaction variable in evaluation of socialising properties of pimozide (Orap).", "A double-blind comparison of pimozide with carpipramine in schizophrenic patients.", "Use of the Social Behaviour Assessment Schedule (SBAS) in a trial of maintenance antipsychotic therapy in schizophrenic outpatients: pimozide versus fluphenazine.", "Weekly pimozide versus fluphenazine decanoate in schizophrenic out-and day-patients.", "[Pimozide and piportil in the treatment of chronic schizophrenia (preliminary communication)].", "Pimozide versus Haloperidol in acute schizophrenia. A double blind controlled study.", "A comparative controlled trial of pimozide and fluphenazine decanoate in the continuation therapy of schizophrenia.", "Prophylactic effects of neuroleptics in symptom-free schizophrenics: roles of dopaminergic and noradrenergic blockers.", "Activity in chronic schizophrenic patients: comparison of pimozide with fluphenazine in a double blind trial.", "Token economy, pimozide and chronic schizophrenia.", "Pimozide in chronic schizophrenic patients.", "A controlled trial of pimozide and trifluoperazine in chronic schizophrenic syndromes.", "Pimozide in chronic schizophrenic outpatients.", "Pimozide versus chlorpromazine in chronic schizophrenia: a 52 week double-blind study of maintenance therapy.", "Pimozide (orap, R 6238) in residual schizophrenia. A clinical evaluation with long-term double-blind follow-up.", "The Scottish first episode schizophrenia study. VII. Two-year follow-up. Scottish Schizophrenia Research Group.", "Once weekly pimozide versus fluphenazine decanoate as maintenance therapy in chronic schizophrenia.", "A standard- (trifluoperazine) controlled clinical study with pimozide in the maintenance treatment of schizophrenic patients, I.", "Intermittent pimozide versus fluphenazine decanoate as maintenance therapy in chronic schizophrenia.", "A double-blind comparison of pimozide and chlorpromazine in the maintenance care of chronic schizophrenic outpatients.", "A comparative double blind trial of pimozide and fluphenazine in chronic schizophrenia.", "Clinical trial of pimozide." ]

[ "Pimozide and haloperidol were found to be equally effective in the treatment of acute schizophrenia in a double-blind clinical trial involving 22 patients. Drug plasma levels measured by radioimmunoassay (RIA) did not correlate with clinical response following either drug. Nor was there any correlation between clinical response and the dopamine receptor blocking activity of either drug as measured by radio receptor assay (RRA). Following pimozide plasma prolactin (PRL) levels correlated with clinical change, although the time courses of response of PRL and clinical response were dissimilar. There was no correlation between PRL and clinical response to haloperidol. RRA and RIA values correlated highly following pimozide but not haloperidol. Our findings lead us to conclude that the RRA technique reflects the plasma level of a drug rather than its central dopamine blocking activity. We also consider that the clinical response to antipsychotic drugs in schizophrenia may be less directly linked to dopamine receptor blockade than has previously been supposed.", "In this study, chronic schizophrenic outpatients who had been maintained on various neuroleptics for an average of about 4 years had their previous medications (approximately equivalent to 695 mg of chlorpromazine per day) changed abruptly to either pimozide or fluphenazine given in single daily oral doses on a double-blind basis for a period of 52 weeks. Average daily doses were pimozide 9.6 mg and fluphenazine 12.5 mg. Measurements of the therapeutic effects of the two drugs were made immediately prior to starting the study, at the end of the 2nd and 4th weeks, and thereafter every 4th week to the end of the study. Three psychometric scales were used for evaluation: Brief Psychiatric Rating Scale (BPRS); Evaluation of Social Functioning (ESFR); and Clinical Global Impressions (CGI). In addition, patients participated in a Social Adjustment Inventory (SAI) evaluation. Statistical analysis with the use of several statistical techniques for between- and within-drug group comparisons revealed that pimozide and fluphenazine were equally effective in maintaining control of symptomatology of chronic schizophrenics at a level commensurate with or better than that provided by their previous medication. Side effects were characteristic of marketed neuroleptics, similar in severity and occurrence between study-drug groups, mainly extrapyramidal symptoms, and readily controlled with antiparkinsonian medication. Pimozide, slightly more potent than fluphenazine, proved to be equally effective for the long-term management of chronic schizophrenic patients.", "nan", "nan", "nan", "nan", "A four week double-blind study comparing pimozide and chlorpromazine was designed to test the hypothesis that pimozide, a powerful dopamine receptor blocker, is more effective in the treatment of acute schizophrenia than chlorpromazine. Twenty patients, 13 males and 7 females ranging in age from 21 to 53 years (mean age 33 years) admitted to ST. Mary's Hospital with acute schizophrenia were placed on the study. They were treated on an individual titrated dosage of either chlorpromazine 300 mg to 2100 mg, or pimozide 10 to 70 mg. The results revealed that on the Brief Psychiatric Rating Scale, the chlorpromazine group significantly improved after one week, whereas the pimozide group showed no statistical improvement until the third week. By the end of the study no significant differences were apparent between the two groups. In the Clinical Global Impression Scale, a significant difference between the two groups was found at week 4 showing a greater improvement in the chlorpromazine group. In terms of adverse reactions, the chlorpromazine group had significantly fewer extrapyramidal symptoms than the pimozide group (Simpson and Angus Scale) and in addition 15 adverse reactions were noted for the pimozide group as compared with 8 for the chlorpromazine group. This study shows that chlorpromazine has an earlier onset of action than pimozide in the acute schizophrenic patient despite the fact that it has a weaker effect on the dopamine receptor than has pimozide. In view of this finding, the dopamine theory of schizophrenia should be critically re-examined.", "nan", "Eighteen chronic, institutionalised patients were randomly assigned to two groups for the purpose of a double blind trial of pimozide (Orap). The results of the study indicated an increase in socialisation, as measured by the Venables scale, for both groups, and no significant difference in this variable between placebo and active preparation groups. It is suggested that greater observer interaction may be responsible for the observed increase in socialisation previously attributed to pimozide.", "nan", "nan", "nan", "nan", "Thirty acutely hospitalized schizophrenic patients were treated under double blind condition with either haloperidol (40-60 mg/day) or pimozide (40-60 mg/day) for 30 days. Ten patients in the pimozide and eleven in the haloperidol group showed a very good or good clinical response. There were no definite differences of treatment results as assessed by the Global Clinical Impression. Both groups showed a statistically significant decrease of the global scores of the Brief Psychiatric Rating Scale (p less than 0.01). There was a significant decrease of affective bluntedness and anergia in the pimozide but not in the haloperidol group. Extrapyramidal side effects were more pronounced in patients on pimozide who therefore needed more anticholinergic drugs. There was no consistent correlation between drug serum levels and global scores or single factors of the BPRS in either treatment group. It is concluded that pimozide in dose ranges from 40-60 mg has powerful antipsychotic properties indistinguishable from those of haloperidol but exerts stronger extrapyramidal side effects.", "Evidence from a controlled, comparative trial indicates that oral pimozide is clinically at least as effective as depot injections of fluphenazine decanoate in the continuation therapy of a group of schizophrenic patients discharged from hospital. The administration of pimozide was associated with fewer unwanted effects. The implications of the findings are discussed.", "A clinical trial was undertaken to determine the role of dopaminergic and noradrenergic blockers in the maintenance treatment of remitted schizophrenics. One hundred and six remitted schizophrenic outpatients were treated with one of nine treatments, viz., thioridazine 25 mg or 75 mg, pimozide 2 mg or 6 mg, and their respective combinations, for 1 year in a double-blind controlled study employing a randomized design. The data from a previous study were utilized as a retrospective placebo group. Pimozide prolonged the number of symptom-free days in a dose-dependent manner and did so more markedly than thioridazine. Combined administration of pimozide and thioridazine prolonged the number of symptom-free days to a greater extent than their single administration. However, an inverted U-shaped dose-response curve was obtained with the combined administration of these agents. These data suggest that both the dopaminergic and noradrenergic blocking action of neuroleptics are important in preventing relapse in remitted schizophrenics.", "A double-blind crossover trial was carried out comparing pimozide with fluphenazine. The effects of the drugs on the activity of 20 chronic inert male schizophrenic patients were measured using nursing observations, psychiatric rating, and an operant conditioning method. When activity was assessed in these different ways, no significant difference was found between the two drugs on any of the measures. It is concluded that pimozide does not effectively increase the activity in such patients. It is considered that the free operant conditioning method used was shown to be a useful measure for comparing therapy in chronic schizophrenic patients.", "Response to a token economy was assessed in male chronic schizophrenic in-patients who were given, in a double-blind cross-over trial, pimozide (up to 20 mg daily) or chlorpromazine )up to 1,000 mg daily), each for three months. After six months there was little change in the patients' mental state, but general ward behaviour and token-rewarded \"target\" behaviours improved significantly. There were no statistically significant between-drug differences, but the trend was that general ward behaviour, but not token-rewarded behaviour, improved more on pimozide. The patients who showed initiative and cooperated best with staff were those whose token-rewarded behaviour was most satisfactory.", "nan", "nan", "In a double blind placebo controlled clinical evaluation of maintenance therapy in chronic schizophrenic female outpatients, thiordazine in single daily doses not exceeding 375 mg./day for 6 months was shown to be effective maintenance treatment compared with PL, thereby establishing the sensitivity of the experiment. Pimozide was also shown to be effective in a single oral dose not exceeding 16 mg./day and comparable overall to the standard drug. The experimental design was based on the anticipated retrogression of PL treated subjects during the 6-month study period, which was reflected in 5 of 9 (56%) \"treatment failures\" in the PL group compared to 2 of 14 (14%) and 2 of 12 (17%) in the THI and PIM groups, respectively. In addition, in some instances improvement over baseline evaluations was noted in both drug groups, particularly on global impression. Though some items of the BPRS exhibited Drug: PL differences, the scale in general was felt to be rather insensitive for this kind of study. Social adjustment ratings on a special scale completed by the patients and families alike, were also found to be insensitive to treatment differences. Side effects most often seen with THI were sedation, EKG and liver function abnormalities. Headache and restlessness occurred most often with PIM. Extrapyramidal symptoms and insomnia were seen most often with PIM and PL equally.", "This study compared the effectiveness and safety of pimozide and chlorpromazine in the maintenance therapy of chronic schizophrenic outpatients. Forty-three patients were assigned in double-blind fashion to one of the drugs for the 52 week study. Both medication groups showed a general pattern of improvement over the course of the study, but there was no significant difference between the two groups. The results demonstrated the effectiveness and safety of pimozide in once daily administration. Previous research results showing the special utility of pimozide for the improvement of emotional withdrawal and social competence in schizophrenia were not replicated.", "nan", "Of 49 schizophrenic patients followed up 2 years after their first admission to hospital, 37% were well, 47% had been readmitted to hospital at some time over the 2 years, and 38% showed schizophrenic symptoms at follow-up. A poor outcome at 2 years was associated with male sex, poor outcome after the first 5 weeks of the first admission, negative schizophrenic symptoms on first admission, and a diagnosis of definite or probable schizophrenia using the Feighner criteria. Only 23% were in employment. A small double-blind discontinuation study of maintenance antipsychotic medication during the second year found more relapses in those switched to placebo medication. Repeat psychometric assessment at 2 years confirmed modest improvements found at 12 months; that is, there was no evidence of intellectual decline. Relatives showed no more psychosocial distress than that found in a normal community sample; what distress there was correlated with patients' schizophrenic symptoms.", "In a double blind trial, 28 male chronic schizophrenic in-patients received either pimozide, given once weekly, or fluphenazine decanoate, given mostly once fortnightly. There was no difference in relapse rates over nine months. However, three-quarters of the patients on pimozide who completed the trial developed at least mild tardive dyskinesia. All patients on pimozide lost weight, the average loss being 5.4 kg (12 lbs). Plasma pimozide levels suggested satisfactory drug compliance. Plasma prolactin levels confirmed that in the pimozide group there was fluctuating dopamine receptor antagonism, while in the fluphenazine group average plasma prolactin levels throughout most of the interval between injections were at the upper limit of normal.", "nan", "In a double-blind trial, 34 male chronic schizophrenic day-patients or in-patients in a hostel ward continued on fluphenazine decanoate given mostly once fortnightly or were switched to pimozide, given on four days each week. Over nine months relapse rates were similar for both groups, and while fewer patients on pimozide were prescribed antiparkinsonian drugs one quarter developed buccolingual masticatory dyskinesia. Plasma pimozide levels suggested satisfactory drug compliance. Average plasma prolactin levels were within the normal rage for untreated men in one quarter of non-relapsing patients on pimozide and three quarters on fluphenazine.", "nan", "nan", "Pimozide and Chlorpromazine were compared in chronic schizophrenics for their therapeutic effectiveness and tolerance, for four-weeks in both cases and for twelve months for pimozide. The minimum and maximum doses were 1 mg to 4 mg single dose for pimozide and 100 to 200 mg thrice daily for chlorpromazine. No significant global differences between the range of therapeutic activity of the two regimens were observed. Slightly more improvement was observed in mood and motor activity with pimozide. Drowsiness and dizziness, and extrapyramidal effects were more prominent with clorpromazine. Other side effects were infrequent. A prolonged improvement in 8 pimozide patients was maintained with mainly weight gain. The advantages of pimozide in chronic unsocialized schizophrenics appear to rest on its single oral daily dose regime, minimal undersirable effects, its specific enhancement of social integration and absence of undersirable effect on mental and physical performance." ]

[ "19504425", "20659937", "18057479", "11759644", "16126045", "17568029", "20206784", "11158461" ]

[ "Comparison of fluconazole and nystatin oral suspensions for prophylaxis of systemic fungal infection in very low birthweight infants.", "Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants.", "Fluconazole prophylaxis against fungal colonization and invasive fungal infection in very low birth weight infants.", "Fluconazole prophylaxis against fungal colonization and infection in preterm infants.", "Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <1000 grams birth weight.", "A multicenter, randomized trial of prophylactic fluconazole in preterm neonates.", "Once-weekly liposomal amphotericin B as Candida prophylaxis in very low birth weight premature infants: a prospective, randomized, open-label, placebo-controlled pilot study.", "Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infant." ]

[ "We compared the efficacy and safety of fluconazole and nystatin oral suspensions for the prevention of systemic fungal infection (SFI) in very low birthweight infants. A prospective, randomized clinical trial was conducted over a 15-month period, from May 1997 through September 1998, in 80 preterm infants with birthweights <1500 g. The infants were randomly assigned to receive oral fluconazole or nystatin, beginning within the first week of life. Prophylaxis was continued until full oral feedings were attained. Blood and urine cultures were obtained at enrollment and then weekly thereafter. Thirty-eight infants were randomly assigned to receive oral fluconazole (group I), and 42 infants were assigned to receive nystatin (group II). Birthweight, gestational age, and risk factors for fungal colonization and SFI at the time of randomization and during the hospital course were similar in both groups. SFI developed in two infants (5.3%) in group I and six infants (14.3%) in group II. The difference between these two rates was not statistically significant (relative risk, 0.37; 95% confidence interval, 0.08 to 1.72). There were no deaths in group I and six deaths in group II (P = 0.03). Two infants died of neonatal sepsis, and four deaths were related to necrotizing enterocolitis and/or spontaneous intestinal perforation. No deaths were due to SFI. Enrollment was halted before completion and the study did not attain adequate power to detect a hypothesized drop in SFI rate from 15 to 5%. Although the results cannot justify any conclusion about the relative efficacy of fluconazole versus nystatin in prevention of SFI, the significantly higher mortality rate in the nystatin group raises questions about the relative safety of this medication.\n Thieme Medical Publishers.", "Invasive fungal infections are a major cause of morbidity and mortality in preterm infants. The authors conducted the first prospective, randomised controlled trial of nystatin compared with fluconazole for the prevention of fungal colonisation and invasive fungal infection in very low birth weight (VLBW) neonates.\n During a 12-month period, all VLBW neonates were assigned randomly to receive nystatin (1 ml suspension, 100 000 U/ml, every 8 h), fluconazole (3 mg/kg body weight, every third day) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). The authors performed weekly surveillance cultures and systemic fungal susceptibility testing.\n During the study period, 278 infants (fluconazole group, n=93; nystatin group, n=94; control group, n=91) weighing <1500 g at birth were admitted. There were no differences in birth weight, gestation, gender or risk factors for fungal infection among the groups. Fungal colonisation occurred in 11.7% of the nystatin group and 10.8% of the fluconazole group, as compared with 42.9% of the control group. The incidence of invasive fungal infection was 4.3% in the nystatin group and 3.2% in the fluconazole group, as compared with 16.5% in the control group. There were no differences in fungal colonisation and invasive fungal infection between the nystatin and fluconazole groups.\n Prophylactic nystatin and fluconazole reduce the incidence of colonisation and invasive fungal infection in VLBW neonates. The authors believe that nystatin is an alternative to fluconazole, because nystatin is safe, inexpensive, well tolerated and effective.", "Fungal infections are common cause of morbidity and mortality in very low birth weight Infants\n To evaluate the efficacy of prophylactic Fluconazole in preventing fungal colonization and invasive fungal infection in VLBW infants.\n Prospective, randomized, double blind placebo controlled clinical trial.\n Tertiary level Neonatal intensive care unit.\n 120 preterm infants with birth Weight < 1500 g.\n Infants were randomly assigned during first three days to receive either Fluconazole or placebo till 28 days or less if, discharged or died earlier. Weekly surveillance cultures from groin, oropharynx, rectum and blood were collected in all patients. Fungal isolates were typed based on standard microbiologic techniques. Liver enzymes were monitored.\n Baseline risk factors for fungal infection in Fluconazole and Placebo groups were similar. Fungal colonization was seen in 30 infants (50%) in the placebo group and 11 infants (19%) in the Fluconazole group (P <0.001). Fungal colonization at rectum, groin and oropharynx was less in fluconazole groups. Fluconazole group showed significantly lower colonizations with Candida albicans but not with C. glabrata. Invasive infection was seen in 15 (25%) infants in Placebo group and 16 (26.7%) infants in Fluconazole group (P = 0.835). Various non-albicans Candida were responsible for 96.8% cases of invasive fungal infection (Candida glabrata 71%, C. parapsilosis 14.7% and C. tropicalis 9.6%). No significant hepatotoxicity was noticed during Fluconazole therapy.\n Prophylactic fluconazole during the first four weeks of life is effective in reducing fungal colonization but not invasive infection in VLBW infants.", "Invasive fungal infection is associated with substantial morbidity and mortality in preterm infants. We evaluated the efficacy of prophylactic fluconazole in preventing fungal colonization and invasive infection in extremely-low-birth-weight infants.\n We conducted a prospective, randomized, double-blind clinical trial over a 30-month period in 100 preterm infants with birth weights of less than 1000 g. The infants were randomly assigned during the first five days of life to receive either intravenous fluconazole or placebo for six weeks. We obtained weekly surveillance cultures from all patients.\n The 50 infants randomly assigned to fluconazole and the 50 control infants were similar in terms of birth weight, gestational age at birth, and base-line risk factors for fungal infection. During the six-week treatment period, fungal colonization was documented in 30 infants in the placebo group (60 percent) and 11 infants in the fluconazole group (22 percent; difference in risk, 0.38; 95 percent confidence interval, 0.18 to 0.56; P=0.002). Invasive fungal infection with positive growth of fungal isolates from the blood, urine, or cerebrospinal fluid developed in 10 infants in the placebo group (20 percent) and none of the infants in the fluconazole group (difference in risk, 0.20; 95 percent confidence interval, 0.04 to 0.36; P=0.008). The sensitivities of the fungal isolates to fluconazole did not change during the study, and no adverse effects of the fluconazole therapy were documented.\n Prophylactic administration of fluconazole during the first six weeks of life is effective in preventing fungal colonization and invasive fungal infection in infants with birth weights of less than 1000 g.", "We tested the hypothesis that twice weekly prophylactic dosing of fluconazole prevents invasive candidiasis without promoting resistant Candida species in high-risk, preterm infants.\n We compared our previous dosing schedule (Group A) to a less frequent dosing schedule of twice a week (Group B) of fluconazole prophylaxis for up to 6 weeks in a prospective, randomized, double-blind clinical trial in preterm infants weighing <1000 grams at birth and with an endotracheal tube and/or central vascular catheter over a 24-month period. Weekly surveillance cultures were obtained on study patients.\n Candida colonization was documented in 5 (12%) of 41 Group A and in 4 (10%) of 40 Group B infants. Candida sepsis developed in two (5%) of Group A and one (3%) of Group B infants (risk difference, -0.02; 95% confidence interval, -0.14-0.10; P=.68). All fungal isolates remained sensitive to fluconazole, and no drug side effects were documented.\n Twice weekly dosing of prophylactic fluconazole can decrease Candida colonization and invasive infection, cost, and patient exposure in high-risk, preterm infants weighing <1000 grams at birth. We speculate that lower and less frequent dosing may delay or prevent the emergence of antifungal resistance.", "Invasive candida infections are a major cause of morbidity and mortality in preterm infants. We performed a multicenter, randomized, double-blind, placebo-controlled trial of fluconazole for the prevention of fungal colonization and infection in very-low-birth-weight neonates.\n During a 15-month period, all neonates weighing less than 1500 g at birth from eight tertiary Italian neonatal intensive care units (322 infants) were randomly assigned to receive either fluconazole (at a dose of either 6 mg or 3 mg per kilogram of body weight) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). We performed weekly surveillance cultures and systematic fungal susceptibility testing.\n Among infants receiving fluconazole, fungal colonization occurred in 9.8% in the 6-mg group and 7.7% in the 3-mg group, as compared with 29.2% in the placebo group (P<0.001 for both fluconazole groups vs. the placebo group). The incidence of invasive fungal infection was 2.7% in the 6-mg group and 3.8% in the 3-mg group, as compared with 13.2% in the placebo group (P=0.005 for the 6-mg group and P=0.02 for the 3-mg group vs. the placebo group). The use of fluconazole did not modify the relationship between colonization and the subsequent development of invasive fungal infection. Overall mortality was similar among groups, as was the incidence of cholestasis. No evidence for the emergence of resistant candida species was observed, but the study did not have substantial power to detect such an effect.\n Prophylactic fluconazole reduces the incidence of colonization and invasive candida infection in neonates weighing less than 1500 g at birth. The benefit of treating candida colonization is unclear. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).\n Copyright 2007 Massachusetts Medical Society.", "This study was conducted to evaluate once-weekly liposomal amphotericin B (L-AmB) for Candida prophylaxis in very low birth weight (VLBW) neonates.\n This prospective, randomized, open-label, placebo-controlled study included neonates who were <32 weeks' gestational age, <7 days old, and weighing <1500 g at birth. Subjects were randomized to receive L-AmB 5 mg/kg per week or placebo (dextrose water) and were followed until 6 weeks of age. Surveillance cultures were obtained at baseline, at 72 hours, and weekly thereafter. Study drug was continued until 6 weeks after birth or the discontinuation of high-risk treatments and invasive devices, whichever occurred first. Blood cultures were obtained as clinically indicated. The primary end point was development of Candida colonization by 6 weeks' postnatal age; secondary end points included development of invasive candidiasis and occurrence of treatment-related adverse events. Safety variables included renal and hepatic function tests, incidence of grade III-IV intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC), and mortality.\n Forty subjects were enrolled and randomized to receive L-AmB (12 males, 8 females; 50% white) or placebo (12 males, 8 females; 35% white). Subjects were evenly distributed by gestational age, age at enrollment, birth weight, race, and sex. Consent was withdrawn after completion of study treatment in 1 subject (L-AmB); 1 subject in each study arm died during the study; and 3 subjects were transferred back to their referring institutions (1 L-AmB, 2 placebo). Thus, 17 subjects in each arm completed all study procedures, although all 40 subjects were evaluable. Colonization before administration of study drug was noted in 4 L-AmB subjects (20%) and 1 placebo subject (5%); 1 (5%) and 3 (15%) subjects in the respective groups developed colonization while receiving study drug. No L-AmB subjects and 1 placebo subject developed candidiasis. One subject in each group died; these deaths were not considered related to study drug or fungal infection. There were no clinical differences between groups in the incidence of grade III-IV IVH, NEC, hypokalemia, nephrotoxicity, need for platelet or packed red blood cell transfusion, or mortality.\n L-AmB 5 mg/kg once weekly was generally well tolerated in these VLBW infants. The data did not allow evaluation of efficacy. A larger, multicenter, randomized clinical trial of L-AmB for Candida prophylaxis that is appropriately powered is warranted.\n Copyright 2010. Published by EM Inc USA.", "Candidal infections are an important cause of morbidity and mortality in the very low birth weight (VLBW) infant. Current intervention focuses on treatment once candidal septicemia is either suspected or diagnosed. Studies have suggested that colonization with candidal species is an important risk factor for subsequent infection.\n To determine whether prophylactic fluconazole for the first 28 days of life results in a decreased incidence of candidal colonization in the VLBW infant.\n Prospective, randomized, controlled, intention-to-treat design comparing prophylaxis with fluconazole versus placebo for the first 28 days of life.\n A tertiary level intensive care nursery in a major teaching hospital in Charleston, South Carolina.\n One hundred three infants with a birth weight of <1500 g, either inborn or outborn, who were admitted to the intensive care nursery between January 1998 and February 1999.\n Infants were enrolled within 72 hours of life with rectal cultures performed on the day of randomization (DOR), as well as day of life (DOL) 7, 14, and 28. Those infants with a birth weight of <1250 g had additional cultures on DOL 35, 49, and 56. Cultures were plated on selective media for isolation of candidal organisms. Infants were randomized to receive either fluconazole (6 mg/kg) or placebo on the DOR. Subsequent doses were given every 72 hours until DOL 7 and then every 24 hours until DOL 28. Medication was given either intravenously or by feeding tube once the infant had been gavage feeding for a 48-hour period without feeding intolerance. Aspartate aminotransferase and alanine aminotransferase levels were obtained on DOR and DOL 7, 14, and 28 to assess for fluconazole toxicity. The minimal inhibitory concentration to fluconazole was determined for all positive cultures to assess the development of resistance.\n The infants who received fluconazole (n = 53) and placebo (n = 50) had no statistical difference in the major risk factors known to increase the chances of candidal septicemia in the VLBW infant. Rectal colonization by candidal species was detected in 8 of the 53 fluconazole-treated patients (15.1%) and in 23 of the 50 infants treated with placebo (46%). Fluconazole significantly reduced rectal colonization from DOL 14 through DOL 56 in all infants with a birth weight of <1250 g, and from DOL 14 through DOL 56 in all infants with a birth weight of 1250 to 1500 g. Alanine aminotransferase levels were higher in the fluconazole versus the placebo-treated group on DOL 14 (18.1 IU/L vs 15 IU/L), but no clinically significant abnormalities were observed. Candida albicans was the most common species isolated. There was no increase in species of Candida noted for their intrinsic resistance to fluconazole, and there was no statistically significant difference in the minimal inhibitory concentrations to fluconazole for all C albicans isolates in either group at any period.\n Prophylactic administration of fluconazole to the VLBW infant for the first 28 days of life is safe and results in a decreased risk of rectal colonization by candidal species. Larger studies to determine the effect of prophylaxis on candidal septicemia and development of resistance in such a selective high-risk group are warranted before initiation of routine prophylaxis.fluconazole, very low birth weight infant, prophylaxis, candidal sepsis, sensitivities to fluconazole." ]

[ "7945477", "1970370", "3281603" ]

[ "Radiologic evidence of disease modification in rheumatoid arthritis patients treated with cyclosporine. Results of a 48-week multicenter study comparing low-dose cyclosporine with placebo. Norwegian Arthritis Study Group.", "Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis.", "Cyclosporin in rheumatoid arthritis: a double blind, placebo controlled study in 52 patients." ]

[ "To evaluate the therapeutic efficacy of 46 weeks of treatment with cyclosporine (5 mg/kg/day) in patients with rheumatoid arthritis (RA).\n A 48-week randomized, double-blind, placebo-controlled, multicenter study of cyclosporine was conducted in 122 patients with active RA. Patients were evaluated by objective and subjective clinical and radiologic measurements at baseline and at the end of the study.\n Statistically significant improvement and clinically important changes were seen for the number of tender joints, number of swollen joints, pain score, duration of morning stiffness, and Lee's functional index in the cyclosporine-treated group at the end of the study. Radiographic examination showed that cyclosporine was capable of retarding joint destruction. In the cyclosporine-treated group, serum creatinine levels increased by 17.5 mumoles/liter (23%) at week 24 and by 21.8 mumoles/liter (26%) at week 48. There was no significant difference in mean serum creatinine levels in patients treated with cyclosporine alone and those treated with cyclosporine plus nonsteroidal antiinflammatory drugs. Five patients had to be treated with antihypertensive drugs, and 2 patients were withdrawn from the study because of increased serum creatinine.\n The study shows that cyclosporine seems to have disease-modifying effects in RA.", "144 patients with severe rheumatoid arthritis from six centres were randomised to receive oral cyclosporin or placebo for 6 months. The initial daily dose of cyclosporin was 2.5 mg/kg, which was increased cautiously with monitoring of serum cyclosporin levels and creatinine; the mean stabilisation dose was 3.8 mg/kg. There were significant improvements in the cyclosporin-treated patients compared with the controls in the major outcomes of reduction of active joints (23% improvement), pain (24%), and functional status (16%); global improvement was 27%. In the cyclosporin group serum creatinine increased by a mean of 15.6 mumols/l and mean arterial blood pressure by 6.27 mmHg; these increases were controlled in all but 2 patients by dose adjustment without withdrawal from the study.", "The efficacy and safety of cyclosporin A (CyA) for patients with rheumatoid arthritis were assessed in a four month double blind, placebo controlled study using an initial dosage of 5 mg/kg daily. Six patients withdrew from the study (two in the placebo group because of inefficacy of treatment and four in the CyA group because of side effects). These six patients were considered therapeutic failures. At the end of the trial the study treatment was considered as good or very good by 14 out of the 26 CyA group patients and by only two out of the 26 placebo group patients. Moreover, in the CyA group significant improvement was observed in five of the seven clinical assessment criteria. Clinical improvement was correlated with a decrease in C reactive protein, alpha 1 glycoprotein levels, and platelet count but not with erythrocyte sedimentation rate or rheumatoid factor titres. Renal toxicity (13 cases) remained the major problem in the management of these patients. This study shows that CyA is effective in active rheumatoid arthritis but requires close monitoring for toxicity." ]