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[ "15064026", "9291741", "21785663", "10227221", "16905024" ]

[ "Role of flies and provision of latrines in trachoma control: cluster-randomised controlled trial.", "Health education and antibiotic therapy in trachoma control.", "Efficacy of latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass antibiotic treatment: a cluster-randomized trial.", "Effect of fly control on trachoma and diarrhoea.", "Intensive insecticide spraying for fly control after mass antibiotic treatment for trachoma in a hyperendemic setting: a randomised trial." ]

[ "Eye-seeking flies have received much attention as possible trachoma vectors, but this remains unproved. We aimed to assess the role of eye-seeking flies as vectors of trachoma and to test provision of simple pit latrines, without additional health education, as a sustainable method of fly control.\n In a community-based, cluster-randomised controlled trial, we recruited seven sets of three village clusters and randomly assigned them to either an intervention group that received regular insecticide spraying or provision of pit latrines (without additional health education) to each household, or to a control group with no intervention. Our primary outcomes were fly-eye contact and prevalence of active trachoma. Frequency of child fly-eye contact was monitored fortnightly. Whole communities were screened for clinical signs of trachoma at baseline and after 6 months. Analysis was per protocol.\n Of 7080 people recruited, 6087 (86%) were screened at follow-up. Baseline community prevalence of active trachoma was 6%. The number of Musca sorbens flies caught from children's eyes was reduced by 88% (95% CI 64-100; p<0.0001) by insecticide spraying and by 30% (7-52; p=0.04) by latrine provision by comparison with controls. Analysis of age-standardised trachoma prevalence rates at the cluster level (n=14) showed that spraying was associated with a mean reduction in trachoma prevalence of 56% (19-93; p=0.01) and 30% with latrines (-81 to 22; p=0.210) by comparison with the mean rate change in the controls.\n Fly control with insecticide is effective at reducing the number of flies caught from children's eyes and is associated with substantially lower trachoma prevalence compared with controls. Such a finding is consistent with flies being important vectors of trachoma. Since latrine provision without health education was associated with a significant reduction in fly-eye contact by M sorbens, studies of their effect when combined with other trachoma control measures are warranted.", "The objective of this study was to confirm whether the combination of a health education programme with a mass treatment campaign was able to improve the effectiveness of trachoma control. An open controlled clinical trial with a 2 x 2 factorial design was carried out. Four villages, matched for size and epidemiological, economic and social conditions, were included in the study. The first village received mass treatment with 1% oxytetracycline eye drops combined with a specific health education programme. The second village received only a health education programme. The third village received only mass treatment and the fourth village did not receive any intervention during the study (control village). 1810 subjects were enrolled of whom 76% were successfully followed for 6 months. The incidence of new cases ranged between 1.6% and 14.2%. In this study the combination of a health education programme with mass treatment failed to increase the cure rate. There was even a negative interaction (P = 0.03). The best results were obtained in the village where antibiotic treatment was used alone, both in terms of cure rate (82%) and reduction of C trachomatis transmission. These results suggest that the addition of a health education programme does not systematically improve the performances of a mass treatment campaign. The efficacy of this combination depends essentially on the capacity of the community to modify its hygiene behaviour.", "The World Health Organization (WHO) recommends environmental improvements such as latrine construction in the integrated trachoma control strategy, SAFE. We report a cluster-randomized trial assessing the effect of intensive latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass treatment with antibiotics.Twenty-four communities in Goncha Seso Enesie woreda, Amhara Regional State, Ethiopia, were enumerated, and a random selection of 60 children aged 0- 9 years in each was monitored for clinical signs of trachoma and ocular chlamydial infection at baseline, 12 and 24 months. All community members were offered treatment with a single dose of oral azithromycin or topical tetracycline. After treatment, 12 subkebeles were randomized to receive intensive latrine promotion. Mean cluster ocular infection in the latrine and the non-latrine arms were reduced from 45.5% (95% CI 34.1-56.8%) and 43.0% (95% CI 31.1-54.8%) respectively at baseline to 14.6% (95% CI 7.4-21.8%) and 14.8% (95% CI 8.9-20.8%) respectively at 24 months (P=0.93). Clinical signs fell from 72.0% (95% CI 58.2-85.5%) and 61.3% (95% CI 44.0-78.5%) at baseline to 45.8% (36.0-55.6%) and 48.5% (34.0-62.9%) respectively at 24 months (P=0.69). At 24 months, estimated household latrine coverage and use were 80.8% and 61.7% respectively where there had been intensive latrine promotion and 30.0% and 25.0% respectively in the single treatment only arm. We were unable to detect a difference in the prevalence of ocular chlamydial infection in children due to latrine construction.", "Domestic flies are accepted vectors of diarrhoea, but their role in trachoma transmission has never been quantified and no study has shown that fly control decreases the prevalence of trachoma. We assessed the effect of fly control on public health in a pilot study in Gambian villages.\n We studied two pairs of villages--one pair in the 1997 wet season, and one pair in the 1998 dry season. For each pair, deltamethrin was sprayed for 3 months to control flies in one village whilst the other was used as a control. Fly populations were monitored with traps. We surveyed trachoma at baseline and at 3 months, and collected daily data on diarrhoea in children aged between 3 months and 5 years.\n Fly control decreased numbers of muscid flies by around 75% in the intervention villages compared with controls. Trachoma prevalence was similar at baseline (wet season, prevalence in intervention village 8.8% vs control 12.2%; dry season, 18.0% vs 16.0%), but after 3 months of fly control there were 75% fewer new cases of trachoma in the intervention villages (wet season 3.7% vs 13.7%; dry season 10.0% vs 18.9%; rate ratio and relative risk of pooled data 0.25 [adjusted 95% CI 0.09-0.64], p=0.003). There was 22% less childhood diarrhoea in the wet season (14% vs 19%, period prevalence ratio 0.78 [0.64-0.95], p=0.01), and 26% less diarrhoea in the dry season (6% vs 8%; 0.74 [0.34-1.59], p=0.60) compared with controls.\n Muscid flies are important vectors of trachoma and childhood diarrhoea in The Gambia. Deltamethrin spray is effective for fly control and may be useful for reducing trachoma and diarrhoea in some situations, but further research on sustainable fly-control methods is needed.", "There are no data on the cumulative effect of fly control and antibiotic distribution on trachoma in hyperendemic communities. We sought to determine whether insecticide spray intervention after mass antibiotic treatment could reduce trachoma and ocular infection with Chlamydia trachomatis in hyperendemic neighbourhoods in Tanzania.\n We did a single-blind, randomised clinical trial in 16 neighbourhoods (balozi) in Kongwa, Tanzania. All children aged 1-7 years were enrolled, with 119 children in the eight balozi of the intervention group and 183 in the eight control balozi. Children were examined at baseline, 6 months, and 1 year for clinical trachoma and ocular C trachomatis infection. One dose of azithromycin was offered to all residents of both intervention and control balozi after the baseline survey. Households (and surrounding areas) in the intervention group were then sprayed with insecticide throughout the ensuing year and monitored for reductions in fly counts. This study is registered at ClinicalTrials.gov, number NCT00347763.\n The intervention balozi had significantly lower fly counts than controls at all monitored weeks (p<0.05), apart from weeks 7-9. The trachoma rate did not differ significantly in the intervention and control balozi at 6 months post-treatment (20%vs 33%, p=0.07), nor did it at 1 year (43%vs 44%, p=0.90). Infection with C trachomatis did not differ between groups at 6 months post-treatment (9%vs 7%, p=0.45).\n Intensive insecticide spraying reduced flies in the environment, but our results suggest that fly reduction after mass antibiotic treatment has no added benefit on reduction of trachoma." ]

[ "17324975", "15068207", "11297052", "17035145", "10842461", "11128878", "16343973" ]

[ "Effect of insulating existing houses on health inequality: cluster randomised study in the community.", "The remediation of mold damaged school--a three-year follow-up study on teachers' health.", "Allergic respiratory disease and fungal remediation in a building in a subtropical climate.", "Reduction in asthma morbidity in children as a result of home remediation aimed at moisture sources.", "Improved health after intervention in a school with moisture problems.", "Respiratory morbidity among children following renovation of a water-damaged school.", "\"The walls were so damp and cold\" fuel poverty and ill health in Northern Ireland: results from a housing intervention." ]

[ "To determine whether insulating existing houses increases indoor temperatures and improves occupants' health and wellbeing.\n Community based, cluster, single blinded randomised study.\n Seven low income communities in New Zealand.\n 1350 households containing 4407 participants.\n Installation of a standard retrofit insulation package.\n Indoor temperature and relative humidity, energy consumption, self reported health, wheezing, days off school and work, visits to general practitioners, and admissions to hospital.\n Insulation was associated with a small increase in bedroom temperatures during the winter (0.5 degrees C) and decreased relative humidity (-2.3%), despite energy consumption in insulated houses being 81% of that in uninsulated houses. Bedroom temperatures were below 10 degrees C for 1.7 fewer hours each day in insulated homes than in uninsulated ones. These changes were associated with reduced odds in the insulated homes of fair or poor self rated health (adjusted odds ratio 0.50, 95% confidence interval 0.38 to 0.68), self reports of wheezing in the past three months (0.57, 0.47 to 0.70), self reports of children taking a day off school (0.49, 0.31 to 0.80), and self reports of adults taking a day off work (0.62, 0.46 to 0.83). Visits to general practitioners were less often reported by occupants of insulated homes (0.73, 0.62 to 0.87). Hospital admissions for respiratory conditions were also reduced (0.53, 0.22 to 1.29), but this reduction was not statistically significant (P=0.16).\n Insulating existing houses led to a significantly warmer, drier indoor environment and resulted in improved self rated health, self reported wheezing, days off school and work, and visits to general practitioners as well as a trend for fewer hospital admissions for respiratory conditions.", "The health effects in teachers of a mold-damaged school before and during an extensive remediation process were assessed. Health data were collected with self-administered questionnaires from teachers (n=31) working in a moisture and mold damaged school and from the reference group of teachers (n=13) working in a non-damaged school. The questionnaire study was repeated three times. Spirometry was measured in 33 individuals in the spring 1997 and repeated in the spring 1999 and 2000. In the damaged school, a cluster of eight asthma cases was identified, the prevalence of asthma being 26%. Before the remediation, the number of sinusitis episodes was higher (p=0.040) and the mean duration of sick leaves longer (p=0.015) among the study group than in the reference group. A higher prevalence of hoarseness and perceived poor quality of indoor air were reported. During the follow-up, no new asthma cases appeared. After the remediation, bronchitis, conjunctivitis, symptoms of allergic rhinitis and the sum of respiratory infection episodes decreased significantly. Some of the asthmatics had low values in the spirometry but no changes in the lung function were observed at the group level. The remediation of the mold damage had beneficial effects on teachers' health.", "An outbreak of allergic respiratory disease occurred in a new building that was characterized from initial occupancy by the presence of extensive visible mold (especially Aspergillus versicolor) on interior surfaces. Epidemiological study of the occupants of both the affected building and a comparison neighboring structure indicated high rates of respiratory and other symptoms among persons working in the affected building. Subsequent clinical evaluations of some persons occupying the building for up to five years identified several cases of building-related allergic respiratory disease, including asthma and hypersensitivity pneumonitis. Based on these findings, the building was evacuated before remediation began. The mycological goal of the three-year building restoration project was to reduce concentration of non-phylloplane fungi such as A. versicolor to the lowest feasible level. All visibly colonized materials in the building were discarded and all fine dust on interior surfaces was removed by vacuuming and/or damp wiping. A medical surveillance program utilizing serial self-reported questionnaires and readily available clinical evaluations was designed to monitor the health of building occupants after re-entry. Symptom rates just prior to building reentry were substantially lower than those found before evacuation and have remained unchanged after re-occupancy was completed. No new or recrudescent cases of illness are known to have occurred after building re-entry.", "Home dampness and the presence of mold and allergens have been associated with asthma morbidity. We examined changes in asthma morbidity in children as a result of home remediation aimed at moisture sources.\n In this prospective, randomized controlled trial, symptomatic, asthmatic children (n = 62), 2-17 years of age, living in a home with indoor mold, received an asthma intervention including an action plan, education, and individualized problem solving. The remediation group also received household repairs, including reduction of water infiltration, removal of water-damaged building materials, and heating/ventilation/air-conditioning alterations. The control group received only home cleaning information. We measured children's total and allergen-specific serum immuno-globulin E, peripheral blood eosinophil counts, and urinary cotinine. Environmental dust samples were analyzed for dust mite, cockroach, rodent urinary protein, endotoxin, and fungi. The follow-up period was 1 year.\n Children in both groups showed improvement in asthma symptomatic days during the preremediation portion of the study. The remediation group had a significant decrease in symptom days (p = 0.003, as randomized; p = 0.004, intent to treat) after remodeling, whereas these parameters in the control group did not significantly change. In the postremediation period, the remediation group had a lower rate of exacerbations compared with control asthmatics (as treated: 1 of 29 vs. 11 of 33, respectively, p = 0. 003; intent to treat: 28.1% and 10.0%, respectively, p = 0.11).\n Construction remediation aimed at the root cause of moisture sources and combined with a medical/behavioral intervention significantly reduces symptom days and health care use for asthmatic children who live in homes with a documented mold problem.", "In a school with floor moisture problems, the personnel had complaints consistent with the sick-building syndrome (SBS). Interventive measures including the laying of a ventilated floor were undertaken to eliminate the emissions. To examine if the intervention resulted in positive health effects, 34 personnel and 336 pupils were interviewed just before the intervention and also 7 months after. Also were interviewed 21 personnel and 224 pupils at an adjacent school serving as a control. Compared with the control school, the problem school showed more complaints, more general symptoms and more symptoms from the eyes, airways and skin, both among the personnel and the pupils. In the post-intervention examinations, the excess of symptoms among the personnel had almost disappeared. Among the pupils, the frequency of eye irritation was reduced but a general improvement of the other symptoms was not as obvious. However, after adjustment for a recent common cold, atopy and stress among the pupils, only one symptom (\"stuffy nose\") remained significantly elevated. In conclusion, the intervention was followed by positive health effects, supporting the hypothesis that emissions from building material had contributed to the excess of symptoms. A recent common cold was highly related to the symptoms and should be considered in future SBS studies.", "The authors sought to determine whether exposure to molds, resulting from moisture damage in a school, was associated with increased respiratory symptoms and morbidity among schoolchildren and whether the renovation of this building resulted in a decrease in prevalence of respiratory symptoms and morbidity. The study was a follow-up (1-y interval) of children between the ages of 7 and 12 y from two elementary schools in a Finnish suburb. In addition to a questionnaire completed by the parents, the authors assessed the respiratory health of children by examining the health records of a local health center. In the cross-sectional study, the prevalence of symptoms and infections were higher in the exposed group, as were visits to a physician and use of antibiotics. The school was renovated, after which all prevalence decreased and no significant differences remained, except for visits to a physician (according to questionnaire responses). Therefore, moisture damage and exposure to molds increased the indoor air problems of schools and affected the respiratory health of children.", "This article reports the findings from an evaluation of a fuel poverty programme in the Armagh and Dungannon Health Action Zone in Northern Ireland. Focusing on a rural community, it adds to the debate surrounding the hidden nature of rural fuel poverty. As part of the programme, energy efficiency measures, including some central heating systems, were installed in 54 homes. Surveys were conducted both pre and post intervention and analysed to assess any changes. The programme demonstrated that energy efficiency intervention can lead to improvements in health and well being, increased comfort levels in the home and a reduction in the use of health services, therefore having potential cost savings for the NHS. Some households, however, remain in fuel poverty after having full central heating installed, reflecting the significant contribution of low income on the production of fuel poverty. The article concludes by suggesting that interventions in this area require commitment from multiple sectors of society, including health professionals and local communities." ]

[ "1634627" ]

[ "A randomized trial of occlusal adjustment in the treatment of periodontitis patients." ]

[ "The purpose of the randomized clinical trial was to test; (1) the influence of occlusal adjustment (OA) in association with periodontal therapy on attachment levels, pocket depth, and tooth mobility, (2) whether OA was of greater significance in non-surgically treated periodontal defects, and (3) whether initial tooth mobility or disease severity had an affect on post-treatment attachment levels following OA. After hygienic-phase therapy, 50 patients received OA/No OA according to random assignment; 22 patients received an OA and 28 were not adjusted. 2 months after OA, either modified Widman flap surgery or scaling and root planing by a periodontist were done according to random assignment within each patient in a split-mouth design. Following active treatment patients were maintained with prophylaxis done every 3 months and scored annually. For the analysis of this two-year data, a repeated measures analysis of variance was performed using attachment level change and pocket depths as outcome indicators. There was significantly greater gain of clinical periodontal attachment in patients who received an OA compared to those who did not. Both the surgically and non-surgically treated sides of the mouth responded similarly to OA. There was no affect of OA on the response in pocket depth, nor did initial tooth mobility or initial periodontal disease severity influence the response to OA." ]

[ "2314786", "9136139", "19785243", "19690792", "20179901", "18004495", "20185357", "16813477", "18094892", "15821528", "17245777", "12887362", "15660184", "19281321", "21425721" ]

[ "Stress urinary incontinence: effect of pelvic muscle exercise.", "Cues to action: pelvic floor muscle exercise compliance in women with stress urinary incontinence.", "Effects of a submaximal exercise protocol to recondition the pelvic floor musculature.", "Pelvic floor muscle training in female stress urinary incontinence: comparison between group training and individual treatment using PERFECT assessment scheme.", "Intensive supervised versus unsupervised pelvic floor muscle training for the treatment of stress urinary incontinence: a randomized comparative trial.", "Nursing intervention to enhance efficacy of home practice of pelvic floor muscle exercises in treating mixed urinary incontinence.", "An alternative intervention for urinary incontinence: retraining diaphragmatic, deep abdominal and pelvic floor muscle coordinated function.", "Effect of pelvic-floor muscle exercise position on continence and quality-of-life outcomes in women with stress urinary incontinence.", "Impact of supervised physiotherapeutic pelvic floor exercises for treating female stress urinary incontinence.", "A randomized controlled trial of duloxetine alone, pelvic floor muscle training alone, combined treatment and no active treatment in women with stress urinary incontinence.", "Short-term efficacy of group pelvic floor training under intensive supervision versus unsupervised home training for female stress urinary incontinence: a randomized pilot study.", "Device to promote pelvic floor muscle training for stress incontinence.", "Paula method of circular muscle exercises for urinary stress incontinence--a clinical trial.", "Randomized trial of circular muscle versus pelvic floor training for stress urinary incontinence in women.", "Effectiveness of pelvic floor muscle training in incontinent women at Maharaj Nakorn Chiang Mai Hospital: a randomized controlled trial." ]

[ "Twenty women with stress urinary incontinence diagnosed by urodynamic testing participated in a 6-week pelvic muscle exercise program. The aim of the study was to evaluate the effectiveness of the exercise program, with or without an intravaginal balloon, on urinary leakage as determined by a 30-minute and a 24-hour pad test. Relative strength of the pelvic muscles was evaluated using an intravaginal device that measures the pressure generated during a muscle contraction. After completion of the exercise program, 18 of the 20 subjects had an increase in strength of the pelvic floor muscles, as demonstrated by increased intravaginal pressure or a decrease in urinary loss on the 24-hour pad test. The use of an intravaginal balloon did not improve performance of the pelvic muscles or decrease urinary loss as compared with the subjects who exercised without an intravaginal balloon. Twelve months after the completion of the exercise program, 19 of the participants responded to a questionnaire about their urinary loss and performance of pelvic muscle exercises. None of the subjects stated that her urinary loss was worse, three had undergone surgical intervention, and ten had not continued to exercise. Seven subjects still exercised, with subjective improvement of urinary loss. It appears that pelvic muscle exercises may be successful in improving the condition of stress urinary incontinence; however, half of the subjects did not continue to exercise independently.", "Pelvic floor muscle exercises are recommended as an initial treatment to women with stress urinary incontinence. This treatment is often unsuccessful because of patient noncompliance. A post-test, experimental control group design was used to examine Pender's (1992) concept of an external cue to action, an audiocassette tape, to enhance patient compliance to pelvic floor exercises. Eighty-six women with urodynamically evaluated stress urinary incontinence participated through a Pelvic Floor Exercise Unit at a large teaching hospital. Patients received biofeedback training and written information to reinforce pelvic floor muscle exercises during a 45-min appointment with a nurse. Patients were instructed to perform the exercises for 10 min twice daily. Forty-three women randomly assigned to an experimental group received an audiocassette tape. Four to 6 weeks later all patients completed a researcher-developed questionnaire that was validity and reliability tested assessing pelvic floor exercise compliance. The 43 patients (100%) who received the audiocassette tape reported compliance with \"routine\" exercises. Twenty-two of 34 patients (65%) who did not receive the tape were compliant (P = 0.0003). Thirty-four of 41 patients (83%) who received the tape reported exercise compliance twice a day, while 4 of 34 patients (12%) in the control group were similarly compliant (P = 0.0000). The findings suggest adding an audiocassette tape to a pelvic floor exercise program enhances patient compliance for incontinent women compared to verbal and written instruction combined with biofeedback.", "Although research has documented the efficacy of maximal voluntary contraction (MVC) exercise for improved pelvic floor muscle (PFM) strength, the efficacy of submaximal voluntary contraction (SVC) exercise for treatment of genuine stress urinary incontinence (GSUI) has not been described.\n To compare the training-induced changes in endurance, strength, and muscle activity recruitment, and continence control in groups of women with GSUI who exercised the PFM using either near-maximal voluntary contraction (NMVC) or SVC effort.\n Training-induced changes in PFM response to exercise were tested by using a quasi-experimental design. Thirty-two women, randomly assigned to either the SVC or NMVC exercise protocol group, were tested before and after training on endurance, muscle contraction strength, muscle activity recruitment, 10-hour weighed pad test for grams of urine loss, and subject-rated severity and frequency of leakage episodes. Repeated measures of specific study variables were retrieved and analyzed from home-training device computer memory and diary records. Changes in muscle activity recruitment, measured as microvolts of electromyogram (EMG) amplitude, were correlated with changes in muscle contraction strength and endurance.\n Increases in muscle contraction strength (t = 1.75; p = 0.045) and decreases in grams of urine leakage (t = -1.86; p = 0.036) were significant for the SVC group. No significant differences were found between the groups for changes in endurance, muscle activity recruitment, frequency of leakage episodes, or subject-rated severity of urine loss based on a 7-point Likert scale.\n Study findings suggest that SVC exercise designed with specificity for gain in neuromuscular control may be beneficial for strengthening the PFM and increasing endurance of contractions to attain and maintain continence in women with GSUI.", "Pelvic floor muscle training (PFMT) is a treatment for stress urinary incontinence (SUI) that can be done individually or in a group. The aim of this study was to compare these two types of treatment.\n Sixty women 30 to 75 years old with SUI were randomly assigned to participate in the two groups. They were evaluated before and after the treatment with the Oxford grading system, pad test, voiding diary, and the King's Health Questionnaire.\n Both groups experienced significant reductions in urinary leakage as measured by the pad test and bladder diary. A negative pad test was observed in about 50% of patients in both groups. There were statistically significant improvements in both muscle strength and quality of life. When the groups were compared, there were no differences in the results between them.\n Individual treatment and group PFMT appear to be equally effective for improving SUI.", "Pelvic floor muscle training (PFMT) is considered to be the first-line treatment for female stress urinary incontinence (SUI). There are few studies that have tested the efficacy of unsupervised PFMT. The aim of this study was to compare the effectiveness of intensive supervised PFMT to unsupervised PFMT in the treatment of female SUI.\n Sixty-two women with SUI were randomized to either supervised or unsupervised PFMT after undergoing supervised training sessions. They were evaluated before and after the treatment with the Oxford grading system, pad test, quality of life questionnaire, subjective evaluation, and exercise compliance.\n After treatment, there were no differences between the two groups regarding PFM strength (p = 0.20), International Consultation on Incontinence Questionnaire-Short Form score (p = 0.76), pad test (p = 0.78), weekly exercise compliance (p = 0.079), and subjective evaluation of urinary loss (p = 0.145).\n Both intensive supervised PFMT and unsupervised PFMT are effective to treat female SUI if training session is provided.", "This study was conducted to evaluate nursing intervention to enhance the efficacy of a home-based pelvic floor muscle exercise (PFME) in treating mixed urinary incontinence among a community-based population. Eighty-eight women with mixed incontinence were recruited for this study and were asked to practice PFME at home as instructed. A registered nurse monitored the study group via telephone checkups twice a week. The Symptoms (LUTS) Questionnaire and a disease-specific questionnaire of impact index were used for repeat measurements before intervention, at 3 and 6 months after PFME. Symptoms such as frequency, nocturia, urge incontinence, and urinary stress incontinence improved significantly in the study group at 6 months. Quality of life with regard to worry about pads/towels leakage and getting wet also improved in the study group at 6 months. Nursing intervention can significantly improve the efficacy of a home-based PFME program in community women with mixed storage symptoms.", "This study was a randomized controlled trial to investigate the effect of treating women with stress or mixed urinary incontinence (SUI or MUI) by diaphragmatic, deep abdominal and pelvic floor muscle (PFM) retraining. Seventy women were randomly allocated to the training (n = 35) or control group (n = 35). Women in the training group received 8 individual clinical visits and followed a specific exercise program. Women in the control group performed self-monitored PFM exercises at home. The primary outcome measure was self-reported improvement. Secondary outcome measures were 20-min pad test, 3-day voiding diary, maximal vaginal squeeze pressure, holding time and quality of life. After a 4-month intervention period, more participants in the training group reported that they were cured or improved (p < 0.01). The cure/improved rate was above 90%. Both amount of leakage and number of leaks were significantly lower in the training group (p < 0.05) but not in the control group. More aspects of quality of life improved significantly in the training group than in the control group. Maximal vaginal squeeze pressure, however, decreased slightly in both groups. Coordinated retraining diaphragmatic, deep abdominal and PFM function could improve symptoms and quality of life. It may be an alternative management for women with SUI or MUI.", "Pelvic-floor muscle (PFM) exercises are effective in reducing stress urinary incontinence (SUI), but few studies have investigated the effect of specific exercise variables on treatment outcomes. This study explored the effect of exercise position on treatment outcomes in women with SUI.\n Forty-four women were randomly assigned to exercise in the supine position only or in both supine and upright positions. Bladder diary, pad test, urodynamic test, quality-of-life (Incontinence Impact Questionnaire [IIQ]), and PFM strength outcomes were obtained at baseline and after treatment.\n Exercise position did not affect outcomes. After data from both groups were collapsed, statistically significant improvements with treatment were observed in bladder diary, IIQ, PFM strength, and urodynamic test results.\n Exercise position did not differentially affect treatment outcomes. However, women in this study achieved a mean 67.9% reduction in the frequency of SUI episodes and improvements in other study outcomes.", "Urinary incontinence is a public health problem that affects more than 200 million people worldwide. Stress incontinence is the most prevalent type. Pelvic floor muscle exercises have been used for treating it, although there is no consensus regarding their application. The aim of this study was to compare the results from treating female stress urinary incontinence with pelvic floor muscle exercises with or without physiotherapist supervision.\n This was a randomized, prospective, controlled trial in the Urogynecology and Vaginal Surgery Sector, Universidade Federal de São Paulo.\n Forty-four women were randomized to be treated for stress urinary incontinence with pelvic floor exercises for three consecutive months, into two groups: one with and the other without physiotherapist supervision. They were evaluated before and after treatment using a quality-of-life questionnaire, pad test, micturition diary and subjective evaluation. Descriptive analysis was used to evaluate the population. The homogeneity of the two groups was evaluated using the Kruskal-Wallis and Chi-squared tests. The success of the two groups after treatment was evaluated using the Wilcoxon test.\n The supervised group showed statistically greater improvement in the pad test, micturition diary and quality of life than did the control group. In the subjective evaluation, only 23.8% of the control group patients were satised with their treatment. In the supervised group, 66.8% of patients did not want any other treatment.\n Supervised pelvic floor muscle exercises presented better results in objective and subjective evaluations than did unsupervised exercises.", "We primarily compared the effectiveness of combined pelvic floor muscle training (PFMT) and duloxetine with imitation PFMT and placebo for 12 weeks in women with stress urinary incontinence (SUI). In addition, we compared the effectiveness of combined treatment with single treatments, single treatments with each other and single treatments with no treatment.\n This blinded, doubly controlled, randomized trial enrolled 201 women 18 to 75 years old with SUI at 17 incontinence centers in the Netherlands, United Kingdom and United States. Women averaged 2 or more incontinence episodes daily and were randomized to 1 of 4 combinations of 80 mg duloxetine daily, placebo, PFMT and imitation PFMT, including combined treatment (in 52), no active treatment (in 47), PFMT only (in 50) and duloxetine only (in 52). The primary efficacy measure was incontinence episode frequency. Other efficacy variables included the number of continence pads used and the Incontinence Quality of Life questionnaire score.\n The intent to treat population incontinence episode frequency analysis demonstrated the superiority of duloxetine with or without PFMT compared with no treatment or with PFMT alone. However, pad and Incontinence Quality of Life analyses suggested greater improvement with combined treatment than single treatment. A completer population analysis demonstrated the efficacy of duloxetine with or without PFMT and suggested combined treatment was more effective than either treatment alone.\n The data support significant efficacy of combined PFMT and duloxetine in the treatment of women with SUI. We hypothesize that complementary modes of action of duloxetine and PFMT may result in an additive effect of combined treatment.", "Current management guidelines propose pelvic floor muscle training (PFMT) as first line treatment for female stress urinary incontinence (SUI). The aim of this study is to compare the efficacy of group PFMT under intensive supervision to that of individual home therapy in women with SUI.\n Thirty women with clinical and urodynamic diagnosis of SUI were randomized in two equal-number groups. Following a common demonstration course, Group A women received a detailed schedule for home training, while Group B in addition attended a weekly hospital group visit. At 12 weeks both groups were assessed for changes in subjective and objective outcomes.\n Twenty-two women, (10 Group A, 12 Group B) with a mean age of 47.3 years completed the study. Although significant (P<0.05) improvements were noted in both groups in quality of life scores, number of incontinence episodes/week, 24-hr frequency, and endurance, repetitions and fast contractions upon vaginal assessment of the PFMs, comparative analysis at the end of the study demonstrated significantly better results for women in Group B, who also improved in daily pad usage, underwear wetting, modified Oxford grading of the PFMs and hold with cough. Consequently, significantly more women in Group B reported improvement in their continence (100% vs. 20% in Group A).\n Group PFMT under intensive supervision produced significantly better improvements in primary and secondary outcomes in the short-term compared to individual, unsupervised home application of PFMT.\n Copyright (c) 2007 Wiley-Liss, Inc.", "Many patients with stress urinary incontinence do not have enough motivation to continue pelvic floor muscle training (PFMT) by themselves. Therefore, a device was created to support PFMT, and its effect was examined.\n Forty-six women with stress urinary incontinence were assigned to a control group or a device group in order of presentation. A pamphlet on PFMT was given to control patients, while the same pamphlet plus the device and instructions on its use were given to patients in the device group. The device had a chime that was set to sound three times a day when exercise sessions were scheduled. PFMT consisted of fast and slow pelvic floor muscle contraction exercises that were performed for 2 min and followed a rhythm set by the device.\n After 8 weeks, 20 patients from the control group and 21 patients from the device group could be evaluated. In the control group, only the quality of life (QOL) index improved significantly. In the device group, however, the daily number of incontinence episodes, the number of pads used daily, the QOL index, and the pad weight in the pad test improved significantly. Patients in the device group said that they felt obligated to perform PFMT when the chime sounded. Forty-eight percent of patients from the device group were satisfied with the outcome of PFMT, while only 15% were satisfied in the control group.\n This device may be useful to support the management of stress urinary incontinence.", "The aim of this study was to determine the efficacy of the Paula method of circular muscle training in the management of stress incontinence (SI). The theory behind this method states that activity of distant sphincters affects other muscles. In a pilot study, 59 women, mainly hospital employees, were randomly assigned to participate in exercises according to the Paula method or pelvic floor training. Efficacy was measured by reports of incontinence, quality of life (I-QOL), pad test, and pelvic floor muscle strength (assessed by perineometer and digital examination). Both the Paula exercises and pelvic floor training produced significant changes in urinary leakage compared to baseline as measured by the pad test [mean decrease of 5.4 g (p=0.002) and 9.5 g (p=0.003), respectively]. Women randomized to the Paula method reported improvement in I-QOL scores. The Paula method was found to be efficacious for SI in a population of Israeli women. Larger community-based studies will be required to confirm these results and enable evaluation of between-group differences.", "Conservative management, such as pelvic floor muscle training (PMFT), is commonly recommended as first-line therapy for women with stress urinary incontinence (SUI).\n We randomly assigned 245 women with SUI to 12 weeks of circular muscle exercises (Paula method) or PMFT in order to assess whether these approaches are equivalent. End points after 12 weeks included urinary leak as measured by a 1-hour pad test, subjective assessment of incontinence, and quality of life (QOL). Cure was defined as urinary leakage of <1 g.\n The mean decrease in urinary leakage was 7.9 g (SD 12.1) among women in the Paula group and 8.9 g (SD 18.2) in the PFMT group (90% confidence interval [CI] of between-group difference was -4.68 g to 3.0 g). This did not meet the prespecified criterion for equivalence. There were 15.2% (p = 0.04) more cures in those randomized to the Paula method. Improvement in subjective urinary complaints and QOL was observed in both groups. The study was limited by a dropout rate of 26.6%.\n Both methods are efficacious in women with SUI. The results suggest superiority of the Paula method in terms of cure rate.", "To compare the effects ofthree different pelvic floor muscle training (PFMT) in stress urinary incontinence (SUI) women.\n Sixty-eight eligible SUI women who could perform pelvic floor muscle contraction correctly were randomly allocated to the three diferent PFMT protocols, exercise every day (GJ), exercise three days per week (G2), and exercise plus abdominal training three days per week (G3). The primary outcome was pad test. The secondary outcomes were pelvic floor muscle strength, and treatment satisfaction. The outcomes were evaluated before and after a 12-week of exercise.\n The weights ofpad were decreased by 2.6 +/- 0.8, 2.3 +/- 1.3, and 3.1 +/- 1.3 grams for group 1, 2, and 3, respectively. There was no statistical significant difference among the three groups. The pelvic floor muscle strength was increased by 18.4 +/- 2.7, 13.9 +/- 2.9, and 17.3 +/- 3.0 cmH2O for group 1, 2, and 3, respectively, with statistical significant difference among groups (p < 0.00). The increased muscle strength in group 2 was significant less than the other two groups (p < 0.00). Treatment Satisfaction showed the leakage was improved with non-significant difference between groups (p > 0.05). No complications were seen in any of the groups.\n Even though the results showed non-significant decrease in pad's weight among the three training groups, the pelvic floor muscle strength were increased in all groups." ]

[ "15924527" ]

[ "TOCOX--a randomised, double-blind, placebo-controlled trial of rofecoxib (a COX-2-specific prostaglandin inhibitor) for the prevention of preterm delivery in women at high risk." ]

[ "To assess the safety and efficacy of the long term prophylactic use of rofecoxib (a COX-2-specific inhibitor) in women at high risk of preterm delivery.\n A randomised, double-blind, placebo-controlled trial.\n Queen Charlotte's and Chelsea Hospital, London and Guys and St Thomas' Hospitals, London.\n Ninety-eight singleton pregnancies at high risk of preterm labour.\n Treatment from 16 to 32 weeks. Weekly ultrasound surveillance.\n Fetal renal function and ductus arteriosus blood flow changes. Preterm delivery rates and neonatal outcome.\n Rofecoxib caused a reduction in hourly fetal urine production rates (-34%, 95% CI -13 to -50%, P = 0.004) and amniotic fluid index (-2.2, 95% CI -3.2 to -1.2, P < 0.001). This effect did not increase with time on treatment and reversed in all cases on discontinuation of treatment. Rofecoxib had an effect on the ductus arteriosus, increasing maximum systolic velocity (0.1 m/s, 95% CI 0.03-0.16, P = 0.02) and minimum diastolic velocity (0.007 m/s, 95% CI 0.0007-0.013, P= 0.03). This effect increased with time on treatment but was reversed with discontinuation of treatment and had no long term clinical sequelae. There was no difference in preterm delivery rates <30 weeks (28% on placebo vs 33% on rofecoxib, Mantel-Haensel [M-H]-adjusted risk 1.11, 95% CI 0.67-1.87). There were more deliveries <37 weeks in those on rofecoxib (40%vs 67%, M-H-adjusted risk 1.59, 95% CI 1.09-2.32). Rates of preterm prelabour rupture of membranes (PPROM) were higher in those on rofecoxib (RR 2.5, 95% CI 1.3-4.7).\n Rofecoxib has a significant but reversible effect on fetal renal function and the ductus arteriosus. It does not reduce the incidence of early preterm delivery <30 weeks and is associated with an increased risk of delivery before 37 weeks in women at high risk." ]

[ "1546834" ]

[ "Effect of indomethacin on bronchorrhea in patients with chronic bronchitis, diffuse panbronchiolitis, or bronchiectasis." ]

[ "Excessive production of sputum is one of the major symptoms in patients with chronic airway diseases. Because endogenous prostaglandins may play a role in the regulation of airway secretions, blockade of cyclooxygenase pathway with indomethacin could decrease respiratory tract fluid and mucus by inhibiting Cl secretion and glandular secretion and by enhancing Na absorption across airway mucosa. To test this hypothesis, we studied the effect of inhaled indomethacin on bronchorrhea in patients with chronic bronchitis, diffuse panbronchiolitis, and bronchiectasis in a double-blind, placebo-controlled fashion. Patients who inhaled 2 ml of indomethacin (1.2 micrograms/ml) three times a day for 14 days showed a decrease in the amount of sputum, from 189 +/- 19 to 95 +/- 21 g/day (p less than 0.001) and an increase in the solid component of sputum without alterations in parameters of systemic inflammatory responses. Although pulmonary function remained unchanged, perceived dyspnea was improved so that Borg's ratio scale was decreased from 7.1 +/- 0.5 to 4.5 +/- 0.4 (p less than 0.01). Adverse effects, including hypotension and bronchoconstriction, were not observed. The reduction of sputum was accompanied by a significant decrease in the concentrations of prostaglandin (PG)E2, PGF2 alpha, thromboxane B2, and 6-oxo-PGF1 alpha in the sputum. Thus, indomethacin inhalation may be of value in reducing bronchorrhea sputum, probably through the inhibition of PG-dependent airway secretions." ]

[ "8885732", "1892185", "2206076" ]

[ "The clinical efficacy of oral tocolytic therapy.", "Oral tocolysis with magnesium chloride: a randomized controlled prospective clinical trial.", "A prospective randomized comparison of oral terbutaline and magnesium oxide for the maintenance of tocolysis." ]

[ "Our purpose was to determine whether maintenance oral tocolytic therapy after preterm labor stabilization decreases uterine activity, reduces the rate of recurrent preterm labor and subsequent preterm birth, or improves neonatal outcome.\n Women with documented idiopathic preterm labor stabilized with acute tocolytic therapy were randomized to three groups: placebo, terbutaline 5 mg, or magnesium chloride 128 mg, all given orally every 4 hours. Patients and providers were blinded to group assignment. All subjects were enrolled in a comprehensive system of preterm birth prevention that included preterm labor education, weekly clinic visits, home uterine contraction assessment, daily phone contact, and 24-hour perinatal nurse access.\n Of the 248 patients who were randomized, 39 were delivered before discharge and 4 were lost to follow-up, leaving 205 for final analysis: 68 placebo, 72 terbutaline, and 65 magnesium. The terbutaline group had significantly more side effects than the placebo group did. All groups had otherwise similar perinatal outcomes when confounding variables were controlled for. Overall, the three groups had a preterm birth rate < 37 weeks of 55.6% delivery, < 34 weeks of 15.6%, a 20.4% rate of newborn intensive care unit admission, and a mean neonatal length of stay of 6.3 days.\n Maintenance oral tocolytic therapy did not decrease uterine activity, reduce the rate of recurrent preterm labor or preterm birth, or improve perinatal outcome. Overall improvement in perinatal outcome may be achieved with a comprehensive program of preterm birth prevention without the use of maintenance oral tocolytic therapy.", "A prospective randomized clinical trial was conducted to assess the efficacy and safety of enteric-coated magnesium chloride (SLOW MAG) as an oral tocolytic agent. Seventy-five patients between 24 and 34 weeks' gestation who were treated with intravenous magnesium sulfate for a first episode of preterm labor were enrolled. After a 12-hour contraction-free period on intravenous therapy, patients were randomized by sealed envelope to one of three groups: group 1, SLOW MAG (535 mg every 4 hours); group 2, oral ritodrine (20 mg every 4 hours); or group 3, no therapy (control). Patients receiving oral therapy were treated until delivery or completion of 36 weeks' gestation. No difference was found between groups with respect to time gained with the use of oral therapy or number completing 36 weeks' gestation. Therapy with enteric-coated magnesium chloride was associated with significantly fewer side effects (20%) as compared with ritodrine (48%) (p less than 0.01). Our results suggest that compared with ritodrine, enteric-coated magnesium chloride is as effective in prolonging pregnancy and preventing recurrent preterm labor. However, neither enteric-coated magnesium chloride nor ritodrine appeared to be any more effective in the prevention of preterm delivery than observation alone.", "We compared oral magnesium oxide with oral terbutaline sulfate in a prospective, randomized manner to determine efficacy and side effects. Preterm labor patients whose labor was arrested with parenteral tocolysis were randomized to oral tocolysis with either magnesium oxide, 200 mg every 3 to 4 hours (n = 23), or terbutaline, 2.5 to 5 mg every 3 to 4 hours (n = 27). The number of patients who were delivered of infants before 36 weeks' gestation was similar between groups (18.5% receiving terbutaline versus 17.4% receiving magnesium). At least one side effect occurred in 81.5% of patients in the terbutaline group and 47.8% in the magnesium group (p less than 0.01). Finally, the cost for 1 day of magnesium (20 cents) is approximately one third the cost of terbutaline (56 cents). These data suggest that oral magnesium oxide is as effective as terbutaline for the maintenance of tocolysis, with fewer side effects and at a lower cost." ]

[ "1123385", "2684990" ]

[ "Acute, complete acromioclavicular separation.", "The management of acute acromioclavicular dislocation. A randomised prospective controlled trial." ]

[ "Twenty-three patients with acute, complete acromioclavicular separation were studied prospectively. Twelve patients were treated non-operatively and eleven were treated operatively. A twelve-month minimum follow-up, using a point system to evaluate clinical results, demonstrated comparable results with and without surgery. Roentgenographic findings did not correlate with the clinical results. Minimum immobilization and early rehabilitation of the shoulder was the recommended treatment of choice.", "In a prospective study, 60 patients with acute acromioclavicular dislocation were randomly allocated to treatment with a broad arm sling or to reduction and fixation with a coracoclavicular screw. Of these 54 were followed for four years. Conservatively-treated patients regained movement significantly more quickly and fully, returned to work and sport earlier and had fewer unsatisfactory results than those having early operation. For severe dislocations, with acromioclavicular displacement of 2 cm or more, early surgery produced better results. Conservative management is best for most acute dislocations, but younger patients with severe displacement may benefit from early reduction and stabilisation." ]

[ "11034885", "7816491", "10678603", "11769869", "1816730", "358926", "9704373", "12800045", "8043247", "8127332", "9552776", "359444", "10685817", "16052120", "8213020", "10478769", "9589535", "11731062", "786825", "15372199", "11444885", "6338860", "15784928", "2896557" ]

[ "Effects of acupuncture, cervical manipulation and NSAID therapy on dizziness and impaired head repositioning of suspected cervical origin: a pilot study.", "Long-term results of cervical epidural steroid injection with and without morphine in chronic cervical radicular pain.", "Treatment of myofascial pain.", "C2/C3 nerve blocks and greater occipital nerve block in cervicogenic headache treatment.", "A comparative study of diazepam and acupuncture in patients with osteoarthritis pain: a placebo controlled study.", "[Comparison of eterilate and acetylsalicylic acid in the treatment of cervicoarthrosis: double blind test].", "A randomized, double-blind, prospective pilot study of botulinum toxin injection for refractory, unilateral, cervicothoracic, paraspinal, myofascial pain syndrome.", "[A prospective double blind study of cervical nerve infiltration with isotonic saline and local anaesthetic].", "Lidocaine injection versus dry needling to myofascial trigger point. The importance of the local twitch response.", "Lack of effect of intraarticular corticosteroids for chronic pain in the cervical zygapophyseal joints.", "Sphenopalatine ganglion block for the treatment of myofascial pain of the head, neck, and shoulders.", "[Ibuprofen in the treatment of the cervicocranial syndrome in combination with manipulative therapy].", "Treatment of whiplash associated neck pain [corrected] with botulinum toxin-A: a pilot study.", "Evidence against trigger point injection technique for the treatment of cervicothoracic myofascial pain with botulinum toxin type A.", "Cervical epidural steroid injection for cervicobrachialgia.", "Chronic spinal pain syndromes: a clinical pilot trial comparing acupuncture, a nonsteroidal anti-inflammatory drug, and spinal manipulation.", "High-dose methylprednisolone prevents extensive sick leave after whiplash injury. A prospective, randomized, double-blind study.", "Botulinum toxin A for the treatment of chronic neck pain.", "[Therapy of cervico-brachialgia. Controlled clinical comparison of a high-dose combination of neurotropic vitamins with an analgesic].", "Comparison of lidocaine injection, botulinum toxin injection, and dry needling to trigger points in myofascial pain syndrome.", "Analgesic effectiveness of subcutaneous carbon-dioxide insufflations as an adjunct treatment in patients with non-specific neck or low back pain.", "Reflex cervical muscle spasm: treatment by diazepam, phenobarbital or placebo.", "Intramuscular ketorolac versus osteopathic manipulative treatment in the management of acute neck pain in the emergency department: a randomized clinical trial.", "Comparative study of high bio-availability glaphenine and paracetamol in cervical and lumbar arthrosis." ]

[ "In a single-subject experiment undertaken on 14 consecutive patients, the effects of acupuncture, cervical manipulation, no therapy, and NSAID-percutan application on kinesthetic sensibility, dizziness/vertigo and pain were studied in patients with dizziness/vertigo of suspected cervical origin. The ability to perceive position of the head with respect to the trunk was studied. The effects of different forms of therapy-and none-on dizziness and neck pain were compared, using a 100 mm visual analogue scale (VAS). Active head relocation by subjects with dizziness was significantly less precise than in the control group. Manipulation was the only treatment to diminish the duration of dizziness/vertigo complaints during the past 7 days and increased the cervical range of motion. Both acupuncture and manipulation reduced dizziness/vertigo on the VAS scale and had positive effects on active head repositioning. Ketoprofen percutan application and acupuncture both alleviated pain. The results of this study would suggest that spinal manipulation may impact most efficiently on the complex process of proprioception and dizziness of cervical origin.\n Copyright 2000 Harcourt Publishers Ltd.", "To evaluate the long-term effectiveness of a single cervical epidural steroid injection (CESI) performed with or without morphine, 24 patients, without need of surgery, but suffering for more than 12 months from cervical radicular pain, were included in a prospective and randomised study. The cervical epidural space was injected (C7-D1; 18-ga needle) with an increasing volume (10 ml maximum) of isotonic saline solution to exacerbate the patient's radicular pain. The patients were then randomly allocated to 2 groups: the steroid group (group S, n = 14) received an equivalent volume of 0.5% lidocaine plus triamcinolone acetonide (10 mg/ml) and the steroid plus morphine group (group S + M, n = 10) received the same combination plus 2.5 mg of morphine sulphate. Pain relief was assessed as the percentage of pain decrease on a visual analogue scale on day 1 and at months 1, 3, 6, 8 and 12 after CESI, up to 48 months. Anthropometric data between the 2 groups were similar. The mean volume injected in the epidural space was: 6.6 +/- 2.1 and 6.3 +/- 1.9 ml in groups S and S + M, respectively, and this volume exacerbated pain in 21 of 24 patients. Despite observing a better transient improvement the day after CESI in the S + M group, long-term results did not differ. The success rate was 78.5% in group S and 80% in group S + M providing pain relief of 86.8 +/- 14.7% and 86.9 +/- 17.9%, respectively. Pain relief remained stable with time (mean follow-up: 43 +/- 18.1 months).(ABSTRACT TRUNCATED AT 250 WORDS)", "To investigate the effectiveness of ultrasound treatment and trigger point injections in combination with neck-stretching exercises on myofascial trigger points of the upper trapezius muscle.\n Depression and anxiety associated with chronic pain were assessed using the Beck Depression Inventory (BDI) and the Taylor Manifest Anxiety Scale (TMAS). The study population comprised 102 patients who had myofascial trigger points in one side of the upper trapezius. The patients were randomly assigned to one of three groups: group 1 received ultrasound therapy to trigger points in conjunction with neck-stretching exercises; group 2 received trigger point injections and performed neck-stretching exercises; and group 3, the control group, performed neck-stretching exercises only. Treatment effectiveness was assessed using subjective pain intensity (PI) with a visual analog scale, pressure pain threshold (PT) with algometry, and range of motion (with a goniometer) of the upper trapezius muscle.\n Compared with the control group, patients in groups 1 and 2 had a statistically significant reduction in PI, an increase in PT, and an increase in range of motion. There were no statistically significant differences between treatment groups 1 and 2. Although not statistically significant, patients in the control group had better results at the 3-mo follow-up. The BDI scores indicated depression in 22.9% of the patient, with 4.8% of the patients having severe depression. High anxiety scores on the TMAS were present in 89.3% of the patients. When BDI and TMAS scores were compared with PI or PT levels, no significant correlations were found, but when compared with pain duration before treatment, correlations were significant.\n Patients with myofascial pain syndrome had higher scores for anxiety than for depression. When combined with neck stretching exercises, ultrasound treatment and trigger point injections were found to be equally effective.", "In the diagnosis of cervicogenic headache, greater occipital nerve (GON), cervical nerve, minor occipital nerve, and cervical facet joint blocks are used. In our study we compared the GON and C2/C3 nerve blocks in the diagnosis and treatment of cervicogenic headache. In both cases, repeated blocks proved to have a long-lasting effect in the treatment of this disorder, with both GON and C2/C3 blocks being found to be equally effective.", "Forty-four patients with chronic cervical osteoarthritis took part in this study. Patients were treated with acupuncture, sham-acupuncture, diazepam or placebo-diazepam in randomized order. Pain was rated on visual analogue scales before, during, and after treatment. Two scales were separately used to rate the intensity (sensory component) and the unpleasantness (affective component) of pain. The results analyzed from these trials show that diazepam, placebo-diazepam, acupuncture and sham-acupuncture have a more pronounced effect on the affective than on the sensory component of pain. Acupuncture was significantly more effective than placebo-diazepam (p less than 0.05), but not significantly more effective than diazepam or sham-acupuncture.", "nan", "In a randomized, double-blind study, two dosage strengths of botulinum toxin type A were compared with normal saline injected into symptomatic trigger points in the cervicothoracic paraspinal muscles.\n To compare the effect of botulinum toxin type A injections with that of normal saline to determine the former's usefulness in the management of neck pain and disability.\n The results of several studies have suggested that botulinum toxin type A may reduce pain associated with myofascial pain syndromes.\n Thirty-three participants were divided randomly to receive either 50 or 100 units of botulinum toxin type A, or normal saline. Patients were re-evaluated over a 4-month period by assessment of their pain and disability and pressure algometer readings, and then offered a second injection of 100 units of botulinum toxin type A.\n All three groups showed significant treatment effects as measured by a decline in the scores on the Neck Pain and Disability Visual Analogue Scale and an increase in the pressure algometer scores. Group differences were apparent only when the authors considered the number of patients who were asymptomatic as a result of the injections.\n Although no statistically significant benefit of botulinum toxin type A over placebo was demonstrated in this study, the high incidence of patients who were asymptomatic after a second injection suggests that further research is needed to determine whether higher dosages and sequential injections in a larger cohort might show a botulinum toxin type A effect.", "Aim of this investigation was the examination of the therapeutic effect of cervical nerve infiltration with mepivacaine in comparison to local applications of isotonic sodium chlorid solution in a prospective randomised double blind study.\n 57 patients with cervicocephalgia or cervicobrachialgia were injected daily with mepivacaine ( n=28) or physiological sodium chlorid solution ( n=29). The success was judged through the blinded patients and blinded therapists first after three days of treatment. If no improvement occurred a single injection of mepivacaine and triamcinolonacetonid was given. This injection could be repeated if required. At the end of the inpatient treatment, after a mean of 14 days, the patients assessed the treatment according to a scale of 1-4 (painfree - no improvement).\n The average therapeutic effect, in the subjective appraisal of 1-4 by the patients, was 2.15 in the mepivacaine-group and 2.54 in the sodium chlorid - group. In the mepivacaine-group no pain (note 1) was achieved two times and 21 times a clear improvement (note 2), while in the sodium chlorid - group 18 times a clear improvement was achieved and never freedom of pain ( p<0,038). In the mepivacaine-group twice a steroidinjection was required, while in the sodium chlorid - group this was necessary in 16 cases ( p<0,01).\n Cervical injections with mepivacaine improve the subjective pain perception in cervicocephalgia and cervicobrachialgia significantly better than isotonic sodium chlorid - solution in short term results and can therefore be prefered. After an inpatient treatment good and excellent subjective results could be achieved in a high percentage.", "This study was designed to investigate the effects of injection with a local anesthetic agent or dry needling into a myofascial trigger point (TrP) of the upper trapezius muscle in 58 patients. Trigger point injections with 0.5% lidocaine were given to 26 patients (Group I), and dry needling was performed on TrPs in 15 patients (Group II). Local twitch responses (LTRs) were elicited during multiple needle insertions in both Groups I and II. In another 17 patients, no LTR was elicited during TrP injection with lidocaine (9 patients, group Ia) or dry needling (8 patients, group IIa). Improvement was assessed by measuring the subjective pain intensity, the pain threshold of the TrP and the range of motion of the cervical spine. Significant improvement occurred immediately after injection into the patients in both group I and group II. In Groups Ia and Ib, there was little change in pain, tenderness or tightness after injection. Within 2-8 h after injection or dry needling, soreness (different from patients' original myofascial pain) developed in 42% of the patients in group I and in 100% of the patients in group II. Patients treated with dry needling had postinjection soreness of significantly greater intensity and longer duration than those treated with lidocaine injection. The author concludes that it is essential to elicit LTRs during injection to obtain an immediately desirable effect. TrP injection with 0.5% lidocaine is recommended, because it reduces the intensity and duration of postinjection soreness compared with that produced by dry needling.", "Chronic pain in the cervical zygapophyseal joints is a common problem after a whiplash injury. Treatment with intraarticular injections of corticosteroid preparations has been advocated, but the value of this approach has not been established. We compared the efficacy of a depot injection of a corticosteroid preparation with the efficacy of an injection of a local anesthetic agent in patients with painful cervical zygapophyseal joints.\n Sixteen men and 25 women with pain in one or more cervical zygapophyseal joints after automobile accidents (mean age, 43 years; median duration of pain, 39 months) were randomly assigned to receive an intraarticular injection of either bupivacaine (0.5 percent) or betamethasone (5.7 mg) under double-blind conditions. The patients were followed by means of regular telephone contact and clinic visits until they reported a return to a level of pain equivalent to 50 percent of the preinjection level. The time from treatment to a 50 percent return of pain was compared in the two groups with the use of a survival analysis.\n Less than half the patients reported relief of pain for more than one week, and less than one in five patients reported relief for more than one month, irrespective of the treatment received. The median time to a return of 50 percent of the preinjection level of pain was 3 days in the 21 patients in the corticosteroid group and 3.5 days in the 20 patients in the local-anesthetic group (P = 0.42).\n Intraarticular injection of betamethasone is not effective therapy for pain in the cervical zygapophyseal joints after a whiplash injury.", "This study examined the effectiveness of sphenopalatine ganglion block (SPGB) for myofascial pain syndrome of the head, neck, and shoulders using a double-blind, placebo-controlled, crossover study design with comparison to an internal standard consisting of trigger point injections (TPI).\n Patients (n = 23) were randomly assigned to receive either: (1) SPGB with 4% lidocaine, then TPI with 1% lidocaine, and finally SPGB with saline placebo or (2) SPGB with saline placebo, then TPI with 1% lidocaine, and finally SPGB with 4% lidocaine. Each respective treatment within each protocol was given sequentially at 1-week intervals for both groups. Prior to the first treatment, all patients assessed their average intensity of pain and pain at that particular moment using a visual analog pain scale. Pain intensity and pain relief were reassessed 30 minutes after each treatment and at 6 hours, 24 hours and 1 week using visual analog pain and pain relief scales. Pain intensity and pain relief data were transformed into natural logarithm units, and the statistical significance of SPGB with 4% lidocaine versus SPGB with placebo, SPGB with 4% lidocaine versus TPI, and TPI versus SPGB with placebo were tested by mixed-model analysis of variance. The magnitude of the differences in pain intensity and pain relief ratings were also compared via computation of 95% confidence intervals.\n The analgesic effect of SPGB with 4% lidocaine was no better than placebo. Mixed-model analysis of variance revealed improved analgesia with administration of TPIs as compared to SPGB with 4% lidocaine and placebo over the entire week of observations (pain relief scores).\n This study suggests that SPGB with 4% lidocaine is no more efficacious than placebo and less efficacious than administration of standard trigger point injections in the treatment of myofascial pain of the head, neck, and shoulders.", "nan", "Up to 87% of patients with whiplash associated disorder (WAD) have some degree of muscle spasm that is contributory to both pain and dysfunction. Botulinum toxin A (BTX-A) produces prolonged muscle relaxation that is dose-dependent and can be easily targeted to affected muscles. BTX-A therapy may be an effective form of therapy offering an alternative or adjunct to conventional modalities. We investigated BTX-A as therapy in patients with WAD.\n This randomized, double blind, placebo controlled study compares outcome measures in 26 patients with chronic neck pain (WAD-II chronic) subsequent to a motor vehicle accident. One-half of the patients received 100 units BTX-A, diluted in 1 ml saline, while the other half received just saline (1 ml). Five trigger points received 0.2 ml each of injectant via a 30 gauge needle. Outcome measures included total subjective neck, shoulder, and head pain based on visual analog scales; objective total range of neck motion (ROM), and the Vernon-Mior subjective function index. Followup assessments were carried out at 2 and 4 weeks post-treatment.\n Fourteen subjects receiving BTX-A and 12 receiving saline completed the study. The treatment group showed a trend toward improvement in ROM and reduction in pain at 2 weeks post-injection. At 4 weeks post-injection the treatment group was significantly improved from preinjection levels (p < 0.01). The placebo group showed no statistically significant changes at any post-treatment time. The Vernon-Mior scale revealed a trend to improvement for both groups.\n BTX-A treatment of subjects with chronic WAD II neck pain resulted in a significant (p < 0.01) improvement in ROM and subjective pain compared to a placebo group, but only a trend to improvement in subjective functioning.", "Traditional strategies for myofascial pain relief provide transient, incomplete, variable, or unpredictable outcomes. Botulinum toxin is itself an analgesic but can also cause sustained muscular relaxation, thereby possibly affording even greater relief than traditional therapies.\n The study goal was to determine whether direct injection of botulinum toxin type A (BoNT-A) into trigger points was efficacious for cervicothoracic myofascial pain, and if so, to determine the presence or absence of a dose-response relation. One hundred thirty-two patients with cervical or shoulder myofascial pain or both and active trigger points were enrolled in a 12-week, randomized, double-blind, placebo-controlled trial. After a 2-week washout period for all medications, patients were injected with either saline or 10, 25, or 50 U BoNT-A into up to five active trigger points. The maximum doses in each experimental group were 0, 50, 125, and 250 U per patient, respectively. Patients subsequently received myofascial release physical therapy and amitriptyline, ibuprofen, and propoxyphene-acetaminophen napsylate. Follow-up visits occurred at 1, 2, 4, 6, 8, and 12 weeks. Outcome measures included visual analog pain scores, pain threshold as measured by pressure algometry, and rescue dose use of propoxyphene-acetaminophen napsylate.\n No significant differences occurred between placebo and BoNT-A groups with respect to visual analog pain scores, pressure algometry, and rescue medication.\n Injection of BoNT-A directly into trigger points did not improve cervicothoracic myofascial pain. The role of direct injection of trigger points with BoNT-A is discussed in comparison to other injection methodologies in the potential genesis of pain relief.", "Fifty patients with chronic resistant cervicobrachialgia were randomly divided into two groups. Twenty-five patients (group A) were treated with cervical epidural steroid/lidocaine injections and 17 patients (group B) were treated with steroid/lidocaine injections into the posterior neck muscles. Another eight patients from group B were excluded from the study because they had started the process of litigation of insurance claims and their subjective analysis of pain relief might therefore not be trustworthy. One to three injections were administered at 2-week intervals according to the clinical response. All patients continued their various pre-study treatments: non-steroidal anti-inflammatory drugs, non-opioid analgesics and physiotherapy. Pain relief was evaluated by the visual analogue scale 1 week after the last injection and then 1 year later. One week after the last injection we rated pain relief as very good and good in 76% of the patients in group A, as compared to 35.5% of the patients in group B. One year after the treatment 68% of the group A patients still had very good and good pain relief, whereas only 11.8% of group B patients reported this degree of pain relief. These differences were statistically significant. We failed to achieve significant improvement of tendon reflexes or of sensory loss in both groups, but the increase in the range of motion, the fraction of patients who were able to decrease their daily dose of analgesics, and recovery of the capacity for work were significantly better in group A. We encountered no complications in either group of patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare needle acupuncture, medication (tenoxicam with ranitidine), and spinal manipulation for managing chronic (>13 weeks duration) spinal pain syndromes.\n Prospective, randomized, independently assessed preintervention and postintervention clinical pilot trial.\n Specialized spinal pain syndrome out-patient unit at Townsville General Hospital, Queensland, Australia.\n Seventy-seven patients (without contraindication to manipulation or medication) were recruited.\n One of three separate, clearly defined intervention protocols: needle acupuncture, nonsteroidal anti-inflammatory medication, or chiropractic spinal manipulation.\n Main outcome measures were changes (4 weeks vs. initial visit) in the scores of the (1) Oswestry Back Pain Disability Index, (2) Neck Disability Index, and (3) three visual analogue scales of local pain intensity.\n Randomization was successful. After a median intervention period of 30 days, spinal manipulation was the only intervention that achieved statistically significant improvements (all expressed as percentages of the original scores) with (1) a reduction of 30.7% on the Oswestry scale, (2) an improvement of 25% on the neck disability index, and (3) reductions on the visual analogue scale of 50% for low back pain, 46% for upper back pain, and 33% for neck pain (all P<.001). Neither of the other interventions showed any significant improvement on any of the outcome measures.\n The consistency of the results provides, in spite of several discussed shortcomings of this pilot study, evidence that in patients with chronic spinal pain syndromes spinal manipulation, if not contraindicated, results in greater improvement than acupuncture and medicine.", "A prospective, randomized, double-blind study comparing high-dose methylprednisolone with placebo.\n To evaluate the efficacy of high-dose methylprednisolone when administered within 8 hours after whiplash injury.\n Whiplash injury often results in chronic symptoms. The management of whiplash injuries is controversial, and pharmacologic therapy has received little evaluation. In recent reports, dysfunction of the central nervous system has been indicated in several cases. Methylprednisolone administered within 8 hours after the injury to patients with acute spinal cord injury has been demonstrated to improve the outcome. This procedure was also adopted in a randomized study of cases of whiplash injury in car accidents.\n Forty patients, 22 men and 18 women with a mean age of 35 years (range, 19-65), were included in the study, 20 in each of two groups. They were treated for whiplash injury, which they had sustained in car accidents. The patients were enrolled if their diagnoses were complete and treatment had begun within 8 hours after injury. Disabling symptoms severe enough to prevent the patient from returning to work, number of sick days before and after injury, and sick-leave profile after injury were used as parameters for the evaluation of the effects of the treatment. Baseline demographic data were controlled for when statistical analysis had been performed.\n At the follow-up examination 6 months after initial treatment, there was a significant difference in disabling symptoms between the actively treated patients and the placebo group (P = 0.047), total number of sick days (P = 0.01), and sick-leave profile (P = 0.003).\n The results of this study indicate that acute treatment with high-dose methylprednisolone may be beneficial in preventing extensive sick leave after whiplash injury. However, the number of patients studied was small, and therefore further prospective, controlled studies are needed.", "A clinical study tested the therapeutic efficacy of Botulinum toxin A (BTXA) when injected into symptomatic neck muscles after one injection session. Patients with chronic neck pain were randomly assigned to receive either a high dose of an active treatment or an injection of the same volume of normal saline. Patients were compared for 4 months using a comprehensive set of outcome measures that included the Neck Pain and Disability Scale (Spine 24 (1999) 1290) and pressure algometry (Arch Phys Med Rehabil 67 (1986) 406; Pain 30 (1987) 115; Clin J Pain 2 (1987) 207). Analyses were consistent in showing significant benefits from the injection session; however, the effects were not specific to the group treated with BTXA. Both treatment and control groups showed a significant decline in pain and disability across time and an increased ability to withstand pressure on trigger points. The heavy incidence of adverse events in the treatment group may partly explain the absence of a treatment effect specific to BTXA. The results show that a single dose treatment without physical therapy is not effective for chronic neck pain.", "The study revealed that cervicobrachialgias (cervical syndrome) can be effectively treated with high-dosed neurotropic vitamins. This refers in particular to pain caused by pressure on the cervical plexus and paravertebral pain on pressur, Regarding paravertebral pain on pressure, it was possible to prove a significant superiority of the therapy with Neurotrat forte. The duration of therapy in both groups was, however, too short in order to prove a significant improvement regarding the lateral listing of the cervical spine. Both forms of treatment produced similar results in view of an improvement of impaired sensibility, paresthesia and alleviation of pain. In both groups side effects were only occasionally observed.", "Myofascial pain syndrome (MPS) is one of the most common causes of chronic musculoskeletal pain. Several methods have been recommended for the inactivation of trigger points (TrP).\n This prospective, single-blind study was proposed to compare TrP injection with botulinum toxin type A (BTX-A) to dry needling and lidocaine injection in MPS.\n Eighty-seven trigger points (cervical and/or periscapular regions) in 23 female and six male patients with MPS were treated and randomly assigned to three groups: lidocaine injection (n=10, 32 TrP), dry needling (n=10, 33 TrP), and BTX-A injection (n=9, 22 TrP).\n Clinical assessment including cervical range of motion, TrP pain pressure threshold (PPT), pain scores (PS), and visual analog scales for pain, fatigue, and work disability were evaluated at entry and the end of the 4th week. Additionally, depression and anxiety were evaluated with the Hamilton depression and anxiety rating scales, and quality of life was assessed using the Nottingham health profile (NHP). The subjects were also asked to describe side effects. INJECTION PROCEDURE: One milliliter of 0.5% lidocaine was administered to each TrP in the lidocaine injection group, 10-20 IU of BTX-A to each TrP in the BTX-A group, and dry needling to each TrP in the last group, followed by stretching of the muscle groups involved. The patients were instructed to continue their home exercise programs.\n Pain pressure thresholds and PS significantly improved in all three groups. In the lidocaine group, PPT values were significantly higher than in the dry needle group, and PS were significantly lower than in both the BTX-A and dry needle groups. In all, visual analog scores significantly decreased in the lidocaine injection and BTX-A groups and did not significantly change in the dry needle group. Disturbance during the injection procedure was lowest in the lidocaine injection group. Quality of life scores assessed by NHP significantly improved in the lidocaine and BTX-A groups but not in the dry needle group. Depression and anxiety scores significantly improved only in the BTX-A-injected group.\n Injection is more practical and rapid, since it causes less disturbance than dry needling and is more cost effective than BTX-A injection, and seems the treatment of choice in MPS. On the other hand, BTX-A could be selectively used in MPS patients resistant to conventional treatments.", "To evaluate the analgesic effectiveness of subcutaneous carbon-dioxide insufflations in addition to standard physical treatment in patients with non-specific neck or low back pain.\n A pragmatic, randomized controlled trial. Setting: Rehabilitation hospital inpatients.\n Patients received either subcutaneous carbon-dioxide insufflations (10 treatments) and standard physical treatment or standard physical treatment only. Outcome measures: Affective pain perception (42-point scale), sensory pain perception (30-point scale), pain intensity (100 mm visual analogue scale).\n Between-groups differences were -2.2 [95% CI -5.2; +0.9] (affective pain perception), -1.2 [-3, 0; + 0.7] (sensory pain perception), and -6.5 [-14; +1.0] (pain intensity) respectively in favour of subcutaneous carbon-dioxide insufflations.\n Subcutaneous carbon-dioxide insufflations do not seem to be a worthwhile adjunct in the given setting of inpatient rehabilitation. Trials in a monotherapeutic setting, which aim more at the efficacy of subcutaneous carbon-dioxide insufflations, might help to solve this issue.", "This double-blind study of the effects of diazepam on painful cervical muscle spasms compared with those of phenobarbital and an inert placebo employed clinical, electrogoniometric and electromyographic recording methods for evaluation and computer analysis. The clinical results were equivocal but the technological recordings revealed a statistically significant greater desirable effect of diazepam compared to the other 2 treatments which would be expected to have only minor nonspecific effects.", "Ketorolac tromethamine injected intramuscularly (IM) has been shown to be an effective analgesic in treating patients with acute musculoskeletal pain in the emergency department (ED). The authors compare the efficacy of a single dose of IM ketorolac to osteopathic manipulative treatment (OMT) as delivered in the ED for the management of acute neck pain. A randomized clinical trial was conducted in three EDs. A convenience sample of 58 patients with acute neck pain of less than three weeks' duration were enrolled. Subjective measures of pain intensity on an 11-point numerical rating scale were gathered from patients immediately before treatment and one hour afterward. Subjects received either OMT or 30 mg, IM ketorolac. Subjects' perceived pain relief was also recorded at one hour after treatment on a subjective 5-point pain relief scale. Twenty-nine patients received IM ketorolac, and 29 patients received OMT. Although both groups showed a significant reduction in pain intensity, 1.7+/-1.6 (P <.001 [95% CI, 1.1-2.3]) and 2.8+/-1.7 (P <.001 [95% CI, 2.1-3.4]), respectively, patients receiving OMT reported a significantly greater decrease in pain intensity (P=.02 [95% CI, 0.2-1.9]). When comparing pain relief at one hour posttreatment, there was no significant difference between the OMT and ketorolac study groups (P=.10). The authors found that, at one hour posttreatment, OMT is as efficacious as IM ketorolac in providing pain relief and significantly better in reducing pain intensity. The authors conclude that OMT is a reasonable alternative to parenteral nonsteroidal anti-inflammatory medication for patients with acute neck pain in the ED setting.", "Seventy-eight patients, 40 suffering from cervical arthrosis and 38 from lumbar arthrosis, received for a period of two weeks paracetamol or a new preparation of glaphenine, in a double blind study. The two drugs were found to have the same efficiency on the subjective parameters but high bioavailability glaphenine seems to have an effectiveness in the range of articulatory movements, which is not found with paracetamol. The side effects were quite equivalent." ]

[ "9800931" ]

[ "A double-blind randomised placebo controlled trial of postnatal norethisterone enanthate: the effect on postnatal depression and serum hormones." ]

[ "To determine the effect of postnatal administration of the long-acting progestogen contraceptive, norethisterone enanthate, on postnatal depression and on serum hormone concentrations, and their association with depression.\n Double-blind randomised placebo-controlled trial.\n A tertiary care hospital in Johannesburg, South Africa. POPULATION Postnatal women using a non-hormonal method of contraception (n = 180).\n Random allocation within 48 hours of delivery to norethisterone enanthate by injection, or placebo.\n Depression scores in the three months postpartum as rated by the Montgomery-Asberg Depression Rating Scale (MADRS) and the Edinburgh Postnatal Depression Scale (EPDS); 2. serum 17beta-oestradiol, progesterone, testosterone and the 17beta-oestradiol:progesterone ratio at six weeks postpartum.\n There was a chance excess of caesarean section deliveries in the progestogen group. Mean depression scores were significantly higher in the progestogen group than in the placebo group at six weeks postpartum (mean MADRS score 8.3 vs 4.9; P = 0.0111; mean EPDS score 10.6 vs 7.5; P = 0.0022). Mean serum 17beta-oestradiol and progesterone concentrations were significantly lower in the progestogen group compared with the placebo group at six weeks postpartum. There were no correlations between any of the hormone parameters and depression at six weeks except in the formula feeding subgroup of the placebo group, where formula feeding and 17beta-oestradiol concentrations were positively associated with depression.\n Long-acting norethisterone enanthate given within 48 hours of delivery is associated with an increased risk of developing postnatal depression and causes suppression of endogenous ovarian hormone secretion." ]

[ "1930699", "3515922", "3515925", "6348714", "2657675", "2813153", "8064454", "3515924", "3515926" ]

[ "The analgesic efficacy of flurbiprofen compared to acetaminophen with codeine.", "Comparison of flurbiprofen and aspirin in the relief of postsurgical pain using the dental pain model.", "Comparative study of flurbiprofen and morphine for postsurgical gynecologic pain.", "Analgesic effect of graded doses of flurbiprofen in post-episiotomy pain.", "An evaluation of flurbiprofen, aspirin, and placebo in postoperative oral surgery pain.", "Evaluation of flurbiprofen, acetaminophen, an acetaminophen-codeine combination, and placebo in postoperative oral surgery pain.", "Analgesic efficacy of flurbiprofen in comparison with acetaminophen, acetaminophen plus codeine, and placebo after impacted third molar removal.", "Comparative study of flurbiprofen, zomepirac sodium, acetaminophen plus codeine, and acetaminophen for the relief of postsurgical dental pain.", "Comparative efficacy of oral flurbiprofen, intramuscular morphine sulfate, and placebo in the treatment of gynecologic postoperative pain." ]

[ "In a single-dose, parallel group, randomized block treatment allocation study, the relative analgesic efficacy of flurbiprofen, a nonsteroidal antiinflammatory drug, was compared to acetaminophen 650 mg with codeine 60 mg, zomepirac sodium 100 mg, and placebo. A total of 226 post-surgical dental patients (146 females and 80 males) participated in the study. Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination. The results of this study support previous work on flurbiprofen.", "This single-dose, double-blind, randomized, placebo-controlled study evaluated the analgesic efficacy of both 25 and 50 mg of flurbiprofen (Ansaid, Upjohn) compared with 650 mg of aspirin and placebo in 164 patients who had undergone dental impaction surgery. Using the highly sensitive dental pain model, flurbiprofen appears to be an effective, peripherally acting analgesic with a rapid onset of activity. In the current study, it was superior to aspirin in terms of peak effect and duration of action. Although flurbiprofen is much more potent than ibuprofen, its side-effect profile did not differ markedly from that of ibuprofen in this single-dose study.", "This single-dose, double-blind, randomized, placebo-controlled study assessed the efficacy and safety of 50 mg of flurbiprofen (Ansaid, Upjohn) in the relief of postoperative pain following cesarean section, as well as vaginal or abdominal hysterectomies. Results show that both 50 mg of oral flurbiprofen and 10 mg of intramuscular morphine sulfate were significantly superior to placebo in 161 patients with respect to pain intensity after medication, pain relief scores, need for additional analgesia, and overall clinical evaluation of pain relief. By two hours after treatment, there were no significant differences between morphine sulfate and flurbiprofen in terms of pain intensity or degree of pain relief. According to investigators' global evaluations of efficacy, both active treatments were statistically superior to placebo. The only adverse reaction occurred in the morphine treatment group. Flurbiprofen administered orally for the relief of moderate to severe pain following major gynecologic surgery appears to be equal to morphine sulfate and superior to placebo in efficacy and safety. Unlike morphine, flurbiprofen is a nonparenteral, uncontrolled substance, and thus patient acceptance is improved while nursing time is decreased.", "Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of flurbiprofen 25, 50 and 100 mg, aspirin 600 mg, and placebo in the relief of moderate to severe post-episiotomy pain. One hundred and fifty-two evaluable patients completed a randomized, double-blind, stratified, parallel groups study. They were observed over a six hour period by one nurse-observer. Based upon each of the summary efficacy measures SPID, TOTAL and PEAK % and most of the hourly direct measures of pain intensity and pain relief, each of the four active treatments were statistically superior to placebo. Flurbiprofen 25 mg appeared to be slightly less effective than aspirin 600 mg, but the differences were not statistically significant. Flurbiprofen 50 and 100 mg were quite similar and were significantly more effective than aspirin 600 mg and flurbiprofen 25 mg. There were no observed or reported adverse effects.", "One hundred sixty-four outpatients with postoperative pain after the removal of impacted third molars were randomly assigned on a double-blind basis, to receive oral doses of flurbiprofen 25, 50, or 100 mg; aspirin 600 mg; or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 8 hours after medicating. Estimates of sum of pain differences (SPID), peak pain intensity difference (PID), total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active medications were significantly superior to placebo. Analgesia was similar for flurbiprofen 25 mg and aspirin 600 mg. Flurbiprofen 50 and 100 mg were significantly superior to aspirin for every measure of analgesia except peak PID. There was a significant dose-response regression between flurbiprofen 25 mg and both of the higher dosages. Flurbiprofen 50 and 100 mg did not differ significantly, suggesting a plateau in flurbiprofen's analgesia. The analgesic effect of flurbiprofen was significant by hour 1 and persisted for 8 hours. The frequency of adverse effects was similar for the active medications.", "Eighty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single, oral dose of flurbiprofen 100 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg with codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medicating. Estimates of sum of pain intensity differences, peak pain intensity differences, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. Flurbiprofen and the acetaminophen-codeine combination were significantly superior to placebo for every measure of total and peak analgesia and significantly superior to acetaminophen alone for most measures of efficacy. Based on the 12-hour data, acetaminophen alone did not differ significantly from placebo; however, it was superior to placebo for measures of total effect based on the 4-hour data. Flurbiprofen was significantly superior to the acetaminophen codeine combination with respect to the number of hours until remedication. All medications had manifested an effect by hour 1; analgesia persisted for 12 hours for flurbiprofen, 6 hours for acetaminophen-codeine, and 3 hours for acetaminophen alone. The frequency of adverse effects was similar for the active medications.", "The analgesic efficacy of 50 and 100 mg flurbiprofen was compared with acetaminophen 650 mg, acetaminophen 650 mg plus codeine 60 mg, and placebo.\n Subjects undergoing the surgical removal of impacted third molars were randomly administered one of the five treatments after the onset of moderate to severe postoperative pain. Pain intensity, pain relief, and side effects were evaluated for 6 hours after drug administration.\n Both doses of flurbiprofen resulted in significant analgesia in comparison with placebo, acetaminophen, and acetaminophen plus codeine as measured by pain intensity difference, pain relief, and global evaluation. The greatest incidence of side effects occurred in the group receiving acetaminophen plus codeine, and the fewest side effects were reported by subjects administered flurbiprofen.\n The results of this study indicate that flurbiprofen is more effective and causes fewer effects than acetaminophen and codeine when used for post-operative dental pain, in ambulatory patients.", "The relative analgesic efficacy and safety of single oral doses of 50 and 100 mg of flurbiprofen (Ansaid, Upjohn) were compared with 100 mg of zomepirac sodium, 650 mg of acetaminophen plus 60 mg of codeine, 650 mg of acetaminophen alone, and placebo in a randomized, double-blind, parallel-group study. A total of 182 patients entered the study with moderate pain from a third molar extraction and were evaluated for six hours. For many efficacy variables, all active treatments were significantly (p less than or equal to 0.05) more effective than placebo. The two doses of flurbiprofen gave approximately similar results, suggesting a plateau effect above 50 mg. With the exception of relief at one hour, there were no significant differences between zomepirac and either dose of flurbiprofen. However, the mean response with zomepirac was greater than with either 50 or 100 mg of flurbiprofen during the first four hours and lower during the last two hours. The analgesic effects of acetaminophen alone were not significantly different from acetaminophen in combination with codeine. At the first hour, acetaminophen plus codeine led to significantly better pain relief than did 100 mg of flurbiprofen. After the first hour, flurbiprofen resulted in greater mean scores than acetaminophen alone or acetaminophen plus codeine, and these differences were significant at the fifth and sixth hours. Five patients had adverse reactions while receiving acetaminophen, acetaminophen plus codeine, or placebo. There were no adverse effects with flurbiprofen or zomepirac.", "This single-dose, double-blind, randomized, placebo-controlled study compared the efficacy of 50 mg of oral flurbiprofen (Ansaid, Upjohn), 10 mg of intramuscular morphine sulfate, and placebo in 92 patients with moderate to severe postoperative gynecologic pain. According to pain intensity, pain relief, and pain intensity difference scores, the morphine-treated patients experienced significantly more pain reduction than the other patients by the first hour after treatment. The flurbiprofen group obtained the same level of significant pain relief as the morphine group by two hours after dosing, but relief persisted longer than in the morphine-treated patients. Evaluation of other efficacy variables revealed similar levels of significant pain reduction in both the flurbiprofen and morphine groups compared with the placebo group. Flurbiprofen was well tolerated and led to fewer side effects than either morphine or placebo." ]

[ "10866882", "10604250", "14762867", "11552215", "20832550", "20372900", "8916821", "9362354", "7689758", "15811482", "8638778", "7529468", "17692642", "12675716", "16035081", "18289228", "16035095", "1712135", "9620500", "8672324", "8475558", "1370735", "10776742", "9249100", "1290169", "16584436" ]

[ "Tranexamic acid reduces red cell transfusion better than epsilon-aminocaproic acid or placebo in liver transplantation.", "A randomized trial of solvent/detergent-treated and standard fresh-frozen plasma in the coagulopathy of liver disease and liver transplantation.", "The prophylactic use of tranexamic acid and aprotinin in orthotopic liver transplantation: a comparative study.", "Aprotinin reduces red blood cell transfusion in orthotopic liver transplantation: a prospective, randomized, double-blind study.", "Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial.", "Effects of low central venous pressure during preanhepatic phase on blood loss and liver and renal function in liver transplantation.", "Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation.", "The prophylactic effect of aprotinin on intraoperative bleeding in liver transplantation: a randomized clinical study.", "Does aprotinin really reduce blood loss in orthotopic liver transplantation?", "Vasopressor administration during liver transplant surgery and its effect on endotracheal reintubation rate in the postoperative period: a prospective, randomized, double-blind, placebo-controlled trial.", "Continuous small-dose aprotinin controls fibrinolysis during orthotopic liver transplantation.", "Comparative effects of small and large aprotinin doses on bleeding during orthotopic liver transplantation.", "Activated recombinant factor VII in orthotopic liver transplantation.", "Comparison of RBCs and FFP with whole blood during liver transplant surgery.", "Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease.", "Coagulation and biochemical effects of balanced salt-based high molecular weight vs saline-based low molecular weight hydroxyethyl starch solutions during the anhepatic period of liver transplantation.", "Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation.", "Aprotinin inhibits tissue plasminogen activator-mediated fibrinolysis during orthotopic liver transplantation.", "Conjugated estrogen reduces transfusion and coagulation factor requirements in orthotopic liver transplantation.", "Improved haemodynamic stability with administration of aprotinin during orthotopic liver transplantation.", "Evidence that intraoperative prostaglandin E1 infusion reduces impaired platelet aggregation after reperfusion in orthotopic liver transplantation.", "Different aprotinin applications influencing hemostatic changes in orthotopic liver transplantation.", "Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study. EMSALT Study Group.", "Continuous small-dose tranexamic acid reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation.", "Antithrombin III supplementation during orthotopic liver transplantation in cirrhotic patients: a randomized trial.", "Comparison of the effects of aprotinin and tranexamic acid on blood loss and red blood cell transfusion requirements during the late stages of liver transplantation." ]

[ "We evaluated the efficacy of the prophylactic administration of epsilon-aminocaproic acid and tranexamic acid for reducing blood product requirements in orthotopic liver transplantation (OLT) in a prospective, double-blinded study performed in 132 consecutive patients. Patients were randomized to three groups and given one of three drugs prophylactically: tranexamic acid, 10 mg. kg(-1). h(-1); epsilon-aminocaproic acid, 16 mg. kg(-1). h(-1), and placebo (isotonic saline). Perioperative management was standardized. Coagulation tests, thromboelastogram, and blood requirements were recorded during OLT and in the first 24 h. There were no differences in diagnosis, Child score, or preoperative coagulation tests among groups. Administration of packed red blood cells was significantly reduced (P = 0.023) during OLT in the tranexamic acid group, but not in the epsilon-aminocaproic acid group. There were no differences in transfusion requirements after OLT. Thromboembolic events, reoperations, and mortality were similar in the three groups. Prophylactic administration of tranexamic acid, but not epsilon-aminocaproic acid, significantly reduces total packed red blood cell usage during OLT.\n In a randomized study of 132 consecutive patients undergoing liver transplantation, we found that tranexamic acid, but not epsilon-aminocaproic acid, reduced intraoperative total packed red blood cell transfusion.", "Virus inactivation of pooled fresh-frozen plasma (FFP) by the solvent/detergent (SD) method results in a loss of approximately 20 percent of factor VIII. This study aimed to assess the efficacy of SD-treated plasma in correcting the coagulopathy associated with liver disease and liver transplantation.\n Forty-nine patients with coagulation deficits due to liver disease, who required FFP for invasive procedures or liver transplantation, were randomly assigned to receive either FFP or SD-treated plasma. Patients were assessed for side effects, correction of coagulopathy over 24 hours, and seroconversion for viral markers 6 to 18 months after treatment.\n In the liver disease group, equal correction of clotting factors and partial thromboplastin time was seen with FFP and SD-treated plasma, with a similar return to baseline values over 24 hours. There was greater correction of the International Normalised Ratio in patients receiving SD-treated plasma (p = 0.037), but this patient group had higher baseline values than recipients of FFP (p = 0.024). Liver transplant patients also showed equivalent correction of coagulopathy with the same dose of FFP and SD-treated plasma. The use of other blood components during transplantation was identical in the two treatment groups. No seroconversions were seen for HIV or hepatitis B or C virus. One patient who had received FFP seroconverted for human parvovirus B19. Apparent seroconversion for hepatitis A virus seen at 9 to 13 months in four other patients was probably due to detection of passively transferred antibodies, as later testing of these patients gave negative results. Minor side effects were rare in both groups.\n SD-treated plasma is an efficacious source of coagulation factors for patients with liver disease who are undergoing biopsy or transplantation. Assessment of seroconversion for viral markers in recipients of plasma-derived products and plasma components should include consideration of the possibility that passively transferred antibodies were detected.", "The efficacy of tranexamic acid (TA) and aprotinin (AP) in reducing blood product requirements in orthotopic liver transplantation (OLT) was compared in a prospective, randomized and double-blind study. One hundred and twenty seven consecutive patients undergoing OLT were enrolled; TA was administered to 64 OLT patients at a dose of 10mg /kg/h and aprotinin was administered to 63 OLT patients at a loading dose of 2 x 10(6) KIU followed by an infusion of 500,000 KIU/h. The portocaval shunt could not be performed in 14 OLT patients in the TA group and in 13 OLT patients in the AP group. However, all OLT patients that received either drug were included in the analysis. Perioperative management was standardized. Hemogram, coagulation tests, and blood product requirements were recorded during OLT and during the first 24 hours. No differences in diagnosis, Child score, preoperative coagulation tests, and intraoperative data were found between groups. No significant differences were observed in hemogram and intraoperative coagulation tests with the exception of activated partial thromboplastin time (aPTT). Similarly, there were no intergroup differences in transfusion requirements. Thromboembolic events, reoperations and mortality were similar in both groups. In conclusion, administration of regular doses of TA and AP during OLT did not result in large differences between the two groups.", "The effect of an aprotinin infusion on blood and blood product transfusion during adult primary orthotopic liver transplantation (OLT) was investigated in a prospective, randomized, double-blind study. Sixty-three patients were enrolled; 33 patients were administered an aprotinin regimen of a 1,000,000-KIU loading dose, followed by a 250,000-KIU/h infusion during surgery, and 30 patients were administered equivalent volumes of normal saline. Red blood cell (RBC) and blood product transfusion intraoperatively and for the first 24 hours postoperatively was by protocol. Intraoperative coagulation testing and thromboelastography (TEG; Hemoscope Corp, Skokie, IL) were performed. Intraoperative RBC transfusion was significantly less in the aprotinin group versus controls: median, 5 units (interquartile range [IQR], 3 to 9 units) versus 7 units (IQR, 5 to 16 units; P =.0016). No significant differences were found for intraoperative blood product transfusion or transfusion of RBCs or blood products in the 24-hour postoperative period. No significant differences were observed in intraoperative coagulation testing or TEG parameters. We conclude that aprotinin infusion reduces RBC transfusion requirements in OLT.", "To test in a prospective randomized study the hypothesis that use of thromboelastography (TEG) decreases blood transfusion during major surgery.\n Twenty-eight patients undergoing orthotopic liver transplantation were recruited over 2 years. Patients were randomized into 2 groups: those monitored during surgery using point-of-care TEG analysis, and those monitored using standard laboratory measures of blood coagulation. Specific trigger points for transfusion were established in each group.\n In patients monitored via TEG, significantly less fresh-frozen plasma was used (mean [SD], 12.8 [7.0] units vs 21.5 [12.7] units). There was a trend toward less blood loss in the TEG-monitored patients; however, the difference was not significant. There were no differences in total fluid administration and 3-year survival.\n Thromboelastography-guided transfusion decreases transfusion of fresh- frozen plasma in patients undergoing orthotopic liver transplantation, but does not affect 3-year survival.\n 2010 Elsevier Inc. All rights reserved.", "Although the low central venous pressure (LCVP) technique is used to decrease blood loss during liver resection, its efficacy and safety during transplant procedures are still debatable. Our study aimed to assess the effects of this technique and its clinical safety for recipients undergoing liver transplantation.\n Eighty-six adult patients were randomly divided into a LCVP group and a control group. In the LCVP group, CVP was maintained below 5 mmHg or 40% lower than baseline during the preanhepatic phase by limiting infusion volume, manipulating the patient's posture, and administration of somatostatin and nitroglycerine. Recipients in the control group received standard care. Hemodynamics, blood loss, liver function, and renal function of the two groups were compared perioperatively.\n A lower CVP was maintained in the LCVP group during the preanhepatic phase, resulting in a significant decrease in blood loss (1922 +/- 1429 vs. 3111 +/- 1833 ml, P < 0.05) and transfusion volume (1200 +/- 800 vs. 2400 +/- 1200 ml, P < 0.05) intraoperatively. Compared with the control group, the LCVP group had a significantly lower mean arterial pressure at 2 h after the start of the operation (74 +/- 11 vs. 84 +/- 14 mmHg, P < 0.05), a lower lactate value at the end of the operation (5.9 +/- 3.0 vs. 7.2 +/- 3.0 mmol/l, P < 0.05), and a better preservation of liver function after the declamping of the portal vein. There were no significant differences in perioperative renal function and postoperative complications between the groups.\n The LCVP technique during the preanhepatic phase reduced intraoperative blood loss, protected liver function, and had no detrimental effects on renal function in LT.", "Patients with end-stage liver disease frequently incur large-volume blood loss during liver transplantation associated with mechanical factors, preexisting coagulopathy, and intraoperative fibrinolysis.\n Between April 1992 and May 1994, the authors of this double-blind, randomized, placebo-controlled study examined the effect of high-dose tranexamic acid (maximum of 20 g) on blood loss and blood product requirements in patients undergoing primary isolated orthotopic liver transplantation. Primary outcome measures were volume of blood loss (intraoperative blood loss and postoperative drainage) and erythrocyte, plasma, platelet, and cryoprecipitate use during surgery and the first 24 h of intensive care unit stay.\n Patients receiving tranexamic acid (n = 25) had less intraoperative blood loss (median, 4.3 l; interquartile range, 2.5 to 7.9; P = 0.006) compared with the placebo group (n = 20; median, 8 l; interquartile range, 5 to 15.8), and reduced intraoperative plasma, platelet, and cryoprecipitate requirements. Median perioperative erythrocyte use was 9 units (interquantile range, 4 to 14 units) in patients receiving tranexamic acid and 13 units (interquantile range, 7.5 to 31 units) in controls (P = 0.03). Total perioperative donor exposure was 20.5 units (interquantile range, 16 to 41 units) in patients receiving tranexamic acid and 43.5 units (interquantile range, 29.5 to 79 units) in controls (P = 0.003). Results for postoperative wound drainage were similar. Hospital stay and need for retransplantation were comparable in both groups. No patient in either group showed clinical evidence of hepatic artery or portal venous thrombosis within 1 month of transplantation.\n High-dose tranexamic acid significantly reduces intraoperative blood loss and perioperative donor exposure in patients with end-stage parenchymal liver disease who are undergoing orthotopic liver transplantation, with marked reductions in platelet and cryoprecipitate requirements.", "Fibrinolysis has been recognized as an important cause of intraoperative bleeding during orthotopic liver transplantation (OLT). Several investigators have used prophylactic administration of aprotinin in patients to inhibit fibrinolysis and to decrease transfusion requirements, morbidity, and mortality. Nevertheless, the role of aprotinin in this situation is not yet clear. The goal of this study was to determine the effects of prophylactic administration of aprotinin on intraoperative bleeding and blood requirements, and on hemostatic changes during OLT. Eighty consecutive patients were included in a double-blind, prospective study and were randomized in two groups. In group A (n = 39), an initial dose of 2 x 10(6) kallikrein inactivator units (KIU) of aprotinin was administered in the induction of anesthesia followed by infusion of 5 x 10(5) KIU/h until the end of the procedure. The control group (n = 41) received an identical volume of saline solution. The majority of the operations were performed with vena cava preservation (piggy-back technique) without venovenous bypass. During the anhepatic phase, a significant increase in levels of tissue plasminogen activator, thrombin-antithrombin complexes (TAT) and D-dimers (DD) was noted in both groups. A significant increment of TAT was observed in group A during reperfusion. The remaining hemostatic parameters were similar in both groups. Intraoperative requirements of packed red cells, fresh-frozen plasma (FFP), platelets, and cryoprecipitate were similar in the two groups. Our results suggest that prophylactic administration of aprotinin is not useful in reducing bleeding and blood product requirements during OLT.", "nan", "End-stage liver disease (ESLD) is associated with a low systemic vascular resistance due to peripheral vasodilatation. This phenomenon is aggravated by general anesthesia (GA) administered during liver transplantation, resulting in precipitous decreases in blood pressure. The excessive amounts (>3 mL/1 mL blood loss) of IV fluid administered to maintain hemodynamic stability during surgery promotes a fluid shift in the lung, which may lead to hypoxia in the immediate postoperative period. This pathophysiologic state may necessitate endotracheal reintubation and mechanical ventilation of the lungs, thus exposing the patient to a risk for morbidities related to laryngoscopy and endotracheal intubation, including deleterious cardiovascular responses to laryngoscopy, endotracheal damage due to laryngoscopic instrumentation, alteration in pulmonary mechanics secondary to controlled mechanical ventilation of the lungs, and delayed recovery associated with the sedation needed to perform these maneuvers.\n The aim of this study was to determine whether the use of a vasopressor to antagonize the vasodilatory effect of GA would reduce the amount of IV fluids administered during liver transplantation, and whether the subsequent amelioration of fluid shift in the postoperative period would reduce the need for ventilatory support and endotracheal reintubation.\n This prospective, randomized, double-blind, placebo-controlled study was conducted at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey. Patients aged > or =18 years scheduled to undergo orthotopic liver transplantation for ESLD were enrolled. The effect of use of an adjuvant vasopressor, together with controlled fluid administration (ie, the volume of IV fluid needed to maintain hemodynamic parameters at > or =80% of preoperative levels) (vasopressor group), was compared with that of fluid administration only (placebo group). We determined various postoperative outcome measures, primarily the amount of fluid administered and the need for endotracheal reintubation.\n Sixty-five patients were enrolled (44 men, 21 women; vasopressor, 33 patients; placebo, 32 patients). Sex distribution showed 19 men and 14 women in the vasopressor group and 25 men and 7 women in the placebo group (both, P < 0.05). The 2 treatment groups were statistically similar with regard to the rest of the baseline demographic and clinical characteristics and duration of surgery. The vasopressor group had a significantly lower prevalence of endotracheal reintubation compared with the placebo group (RR, 1:6; P < 0.05). The other postoperative parameters were statistically similar between the 2 groups.\n In this study of adults undergoing orthotopic liver transplantation for ESLD, use of an adjuvant vasopressor, together with controlled fluid administration, to maintain a stable hemodynamic status during GA reduced the need for endotracheal reintubation and its associated morbidities in the postoperative period compared with placebo.", "Large doses of aprotinin (1,000,000-2,000,000 kallikrein inhibitor units [KIU] initial dose and a 500,000 KIU/h infusion) have been used during orthotopic liver transplantation (OLT) to reduce the incidence and severity of fibrinolysis. This double-blinded study was designed to investigate whether a small-dose infusion of aprotinin (200,000 KIU/h) would control fibrinolysis. A controlled study was undertaken to compare small-dose aprotinin with a placebo in patients undergoing OLT with veno-venous bypass. Forty-four patients were randomized either to the aprotinin group (n = 21), which received an intravenous infusion of 200,000 KIU/h without an initial dose, or to a control group (n = 23), which received normal saline. Coagulation variables, thrombelastograms, and postoperative blood drainage were measured. Blood levels of fibrin degradation products (FDP) were significantly higher in the control group (95% > 20 micrograms/mL) at the end of surgery compared to the aprotinin group (53% > 20 micrograms/mL, P < 0.01). The transfusion of cryoprecipitate units was more in the control group versus the aprotinin (12.6 +/- 12.8 vs 5.7 +/- 7.5; P < 0.04), as was the number of fresh frozen plasma units (6.6 +/- 3.5 vs 3.6 +/- 6.1; P < 0.05). We conclude that an infusion of a small dose of aprotinin can safely control fibrinolysis during liver transplantation with a concomitant reduction in transfusion of blood products.", "Large prophylactic doses of aprotinin efficiently reduce blood loss during orthotopic liver transplantation (OLT). Small doses of aprotinin are usually used to treat fibrinolysis. However, no studies have investigated the benefit of prophylactic administration of a smaller dose of aprotinin during liver transplantation. We compared two methods of aprotinin therapy on transfusion outcome in liver transplant patients in a prospective study of 199 patients undergoing OLT who were randomized to large or small prophylactic doses of aprotinin during the transplant procedure. In the large-dose group (n = 94) an initial dose of 2,000,000 kallikrein inactivation units (KIU) was followed by infusion of 500,000 KIU/h until the patient's return to the intensive care unit. In the small-dose group (n = 95), an initial dose of 500,000 KIU was followed by an infusion of 150,000 KIU/h. Outcome measurements included intraoperative transfusion requirements (packed red blood cells, fresh frozen plasma, platelets, intraoperative salvage) and postoperative hematologic values. There were no differences in transfusion requirements in the two groups of patients. Patients treated with low-dose aprotinin had slightly higher postoperative fibrinogen concentrations. Large-dose aprotinin therapy does not appear to offer additional benefit compared to low-dose aprotinin administration.", "Orthotopic liver transplantation (OLT) is affected by important alterations of hemostasis. The aim of this study was to evaluate the efficacy of recombinant factor VII activated (rFVIIa) to reduce intraoperative bleeding during OLT.\n Twenty OLT patients were assigned in double-blind way to a rFVIIa group or a control group. Inclusion criteria were hemoglobin > 8 g/dL: INR > 1,5 and fibrinogen > 100 mg/dL. We administered a single bouls of rFVIIa (40 microg/kg) or placebo. We determined INR, partial thromboplastin time, fibrinogen, ATIII, and blood cell counts. Blood products were administered as follows: 4 units of fresh frozen plasma when INR > 1.5, and 1 unit of RBC for Hb < 10 g/dL. The study ended 6 hours after the bolus.\n No thromboembolic events occurred. The INR was different between rFVIIa group and the controls at T0 (1.9 vs 1.6 P < .021) and during T1 (1.2 vs 1.6 P < .004). The total transfused red blood cells was 300 mL +/- 133 in rFVIIa group and 570 mL +/- 111 in control group (P < .017). The total fresh frozen plasma was 600 mL +/- 154 in rFVIIa group and 1400 mL +/- 187 in control group (P < .001). Total blood loss was greater in the control group than the rFVIIa group: 1140 mL +/- 112 vs 740 mL +/- 131 (P < .049).\n The use of rFVIIa during OLT can reduce the risk of bleeding during surgery. The literature has described cases who did not benefit from the treatment. An adequate cut-off of INR, allowed us to treat only patients at greater bleeding risk.", "Component therapy has become the accepted standard of care in transfusion medicine. In instances of large blood loss, the transfusion of whole blood rather than the combination of RBCs and FFP is rational and may be preferred.\n In a controlled, prospective, randomized study of 33 patients undergoing orthotopic liver transplantation, the effectiveness of component therapy (RBCs and FFP) was compared with the use of whole blood. Coagulation tests (prothrombin time and activated partial thromboplastin time), clotting factor levels (FV, FVIII, fibrinogen), platelet counts, the number of donor exposures, and the total volume of blood transfused for the whole-blood group and the component-therapy group were compared at designated times before surgery, during surgery, and 24 hours after surgery.\n There was a significant difference (p=0.015) in the median number of donor exposures for RBCs and FFP, with fewer occurring in the whole-blood group (n=14.5) compared with the component group (n=25). There was no significant difference between groups in coagulation profiles during any of the phases of surgery except for a mild decrease in fibrinogen levels in the whole-blood group at the conclusion of surgery. There were no differences between the groups in the median volume of blood component replacement, the median age of blood components, the patients' Hct or the number of RBC-containing components transfused.\n Whole blood, when compared with component therapy, is associated with fewer donor exposures yet provided equally effective replacement therapy for blood loss in liver transplantation patients.", "Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this double-blind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 microg/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required.", "The anhepatic period of liver transplantation is generally marked by a decrease in preload, and the infusion of hydroxyethyl starch (HES) solution is often an effective way to restore volume deficits in non-anaemic patients. However, the infusion of even limited amounts of HES solution during the anhepatic period may result in a worsening coagulopathy. Moreover, lactate-containing HES solution may cause some degree of biochemical derangements in compromised recipients. Therefore, we compared two different types of HES solutions: a balanced salt-based high molecular weight HES solution (670/0.75; high MW group) and a saline-based low molecular weight HES solution (130/0.4; low MW group) with respect to coagulation and biochemical profiles. First, in an in vitro study (n = 48), thromboelastography was performed to determine the effects of two HES solutions on coagulation after diluting (11%) the recipient's blood sample with each HES solution. Second, in an in vivo study, 500 ml of one of the two 6% HES solution was administered to 74 recipients (n = 37, each group) for 30 min after starting the anhepatic period. The coagulation profiles, including thromboelastography, and biochemical profiles were measured before and 30 min after the end of infusion. Less impairment in the thromboelastography profiles and aPTT was observed in the high MW group. A higher calcium concentration and less reduction in platelet count were noted in the high MW group, but lactate accumulation was greater. In conclusion, a balanced salt-based high molecular weight HES solution is a more effective volume replacement during the anhepatic period of liver transplantation with respect to coagulation than a saline-based low molecular weight HES solution, although lactate accumulation is a possible concern.", "Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double-blind, placebo-controlled trial enrolled patients undergoing OLT because of cirrhosis (Child-Turcotte-Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 microg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo.", "nan", "We conducted a prospective, randomized study to determine the efficacy of conjugated estrogen in reducing blood product transfusion during orthotopic liver transplantation (OLT). Patients undergoing OLT were included in the study. Only those having a reaction time of more than 30 mm or 15 min (19 -28 mm) on computed thromboelastography (CTEG) at the beginning of surgery were enrolled in the study. Patients were randomized to receive either conjugated estrogen (CE) or placebo. Every patient received a first dose of CE (100 mg i.v.) (20 mL) or placebo (20 mL of isotonic sodium chloride solution) at the beginning of the procedure and a second dose of CE (100 mg i.v.) or 20 mL of placebo (20 mL of isotonic sodium chloride solution) just after reperfusion of the new graft. The two groups were similar in age, weight, requirement for veno-veno bypass, time on veno-veno bypass, CTEG measurement, and preoperative hemoglobin and platelet values. Blood products were given in relation to hematocrit and coagulation (CTEG) variables, which were measured every hour during the surgery. The amount of transfused blood products did not differ in terms of units of cryoprecipitate, but the intraoperative requirements for red blood cells (6 +/- 3 vs 9 +/- 6 U; P = 0.05), platelets (12 +/- 8 U vs 18 +/- 10 U; P = 0.05) and fresh-frozen plasma (3 +/- 3 U vs 6 +/- 4 U; P = 0.001) was significantly less in the estrogen group than in the control group. We conclude that CE is associated with a significant decrease in use of fresh-frozen plasma, platelets, and red blood cells during OLT. Implications: In this study, we prospectively investigated whether i.v. conjugated estrogen could decrease blood product transfusion during orthotopic liver transplantation. Conjugated estrogen-treated patients received less fresh-frozen plasma, red blood cells, and platelets. In this population of patients, conjugated estrogen can be a useful addition in coagulation management during orthotopic liver transplantation.", "In a placebo-controlled, double-blind study, we have investigated the hypothesis that patients for orthotopic liver transplantation (OLT) treated with high-dose aprotinin (serum concentrations > or = 200 kiu ml-1) show greater haemodynamic stability on graft reperfusion. We studied 55 adult patients presenting for OLT, and 52 were included in the analysis. The treatment and placebo groups were similar in patient characteristics. The anaesthetic regimen used was standardized, and veno-venous bypass were used in all patients. Cardiac output measurements and haemodynamic profiles were recorded at intervals throughout anaesthesia and surgery. Arterial and mixed venous oxygen saturations were measured by co-oximetry. Derived variables were measured using standard formulae. Aprotinin treated patients had greater values for systemic vascular resistance on reperfusion, with a lesser cardiac index and calculated oxygen delivery. Oxygen consumption, however, was significantly greater, despite reduced delivery.", "Recent investigations measuring platelet aggregation during 10 orthotopic liver transplantations showed a significant decrease in platelet aggregation immediately after reperfusion and in the perfusate. As prostaglandin E1 has been shown to exhibit a beneficial effect in the treatment of ischemic injury of the liver, we investigated in a prospective, randomized, and open study the effect of PGE1 infusion during OLT on platelet function. Ten patients were randomized to receive a continuous PGE1 infusion (PG group) and another ten patients served as controls. Platelet function was determined ex vivo by measuring the adenosine diphosphate-, collagen-, and ristocetin-induced aggregation in platelet-rich plasma. A significantly higher platelet aggregability was measured in the PG group throughout the whole operation for ADP (1 and 2 mumol/L) and collagen (0.5 micrograms/ml). The same was true for collagen (1 microgram/ml) and ristocetin (1.2 mg/ml) after reperfusion. Not only the postreperfusional decrease in platelet aggregation but also the decline in platelet count that occurred in the control group could be prevented greatly by PGE1 infusion. In the perfusate, released from the liver graft vein by flushing with arterial blood, a significantly lower platelet aggregability was seen in comparison with the systemic circulation before reperfusion in the control group, a difference that was not found when PGE1 infusion was given intraoperatively. However, blood product requirements during OLT were comparable in both groups. In conclusion, PGE1 therapy during OLT preserves platelet function and prevents the drop in platelet count observed in the control group after revascularization.", "The effect of different aprotinin applications on hemostatic changes and blood product requirements in orthotopic liver transplantation was investigated in a prospective, open, and randomized study. From November 1989 to June 1990, 13 patients received aprotinin as a bolus of 0.5 Mill. Kallikrein inactivator units (KIU) on three occasions in the course of an OLT, whereas 10 other patients were treated with continuous aprotinin infusion of 0.1-0.4 Mill. KIU/hr. Before and after reperfusion of the graft liver, signs of hyperfibrinolysis, measured by thrombelastography, were significantly lower in the infusion group. Tissue-type plasminogen activator (t-PA) activity increased during the anhepatic phase but to a significantly lesser extent in the infusion group. Blood product requirements during OLT were tendentiously higher in the bolus group but not significantly so. However, the use of packed red blood cells was significantly lower in the postoperative period, whereas there was no significant difference in fresh frozen plasma requirements between the two groups. All 23 patients have survived, and only one woman of each group required retransplantation due to severe host-versus-graft reactions. Furthermore, we investigated the perfusate of the graft liver in both groups and detected signs of a decreased t-PA release in the infusion group. Our results demonstrate an advantage of aprotinin given as continuous infusion over bolus application in OLT.", "Intraoperative hyperfibrinolysis contributes to bleeding during adult orthotopic liver transplantation. We aimed to find out whether aprotinin, a potent antifibrinolytic agent, reduces blood loss and transfusion requirements.\n We did a randomised, double-blind, placebo-controlled trial in which six liver-transplant centres participated. Patients undergoing primary liver transplantation were randomly assigned intraoperative high-dose aprotinin, regular-dose aprotinin, or placebo. Primary endpoints were intraoperative blood loss and transfusion requirements. Secondary endpoints were perioperative fluid requirements, postoperative blood transfusions, complications, and mortality.\n 137 patients received high-dose aprotinin (n=46), regular-dose aprotinin (n=43), or placebo (n=48). Intraoperative blood loss was significantly lower in the aprotinin-treated patients, with a reduction of 60% in the high-dose group and 44% in the regular-dose group, compared with the placebo group (p=0.03). Total amount of red blood cell (homologous and autologous) transfusion requirements was 37% lower in the high-dose group and 20% lower in the regular-dose group, than in the placebo group (p=0.02). Thromboembolic events occurred in two patients in the high-dose group, none in the regular-dose group, and in two patients in the placebo group (p=0.39). Mortality at 30 days did not differ between the three groups (6.5%, 4.7%, and 8.3%; p=0.79).\n Intraoperative use of aprotinin in adult patients undergoing orthotopic liver transplantation significantly reduces blood-transfusion requirements and should be routinely used in patients without contraindications.", "Tranexamic acid (TA) is a synthetic drug that inhibits fibrinolysis. It has been administered to decrease the use of blood products during cardiac surgery and orthotopic liver transplantation when infused in larger doses. A small-dose infusion of aprotinin causes a reduction in fibrinolysis and blood product requirement during orthotopic liver transplantation without apparent risk of intravascular thrombosis. This prospective study was designed to investigate whether a small-dose infusion of TA would be equally effective in reducing fibrinolysis and blood product transfusions during orthotopic liver transplantation. A double-blind, controlled study was undertaken to compare the efficacy of a small-dose TA infusion with that of a placebo. Thirty-two consecutive patients were randomized either to the TA group (n = 16), which received an intravenous infusion of 2 mg x kg(-1) x h(-1), or to the control group (n = 16), which received an identical volume of normal saline. Coagulation values were measured, a field rating was made by the surgeon, and a thromboelastogram was produced at four predetermined intervals throughout the case-before TA infusion was started, after portal vein ligation, 10 min after reperfusion, and at the end of surgery. Intraoperative transfusion requirements were recorded during the procedure and for the first 24 h postoperatively. A record was kept of any intraoperative epsilon-aminocaproic acid administered for uncontrolled fibrinolysis. The thromboelastogram clot lysis index was significant for lysis in the control group during both the anhepatic and the neohepatic phases (P < 0.01 and P < 0.05, respectively) when compared with the TA group. Fibrin degradation products were significantly increased (>20 microg/mL) in the control group at reperfusion (P < 0.03) and at the end of surgery (P < 0.01). D-dimers were also significantly increased (>1 mg/L) in the control group at the end of surgery (P < 0.04). Nine of the 16 control patients versus 3 of the 16 TA patients required epsilon-aminocaproic acid rescue for fibrinolysis. There were no other significant differences between groups. Transfusion requirements during surgery and for the first 24 h postoperatively did not differ significantly between the two groups. We conclude that the use of small-dose TA reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation.", "Severe intraoperative bleeding is one of the main problems during liver transplantation. Acquired hemostatic defects, namely primary or secondary hyperfibrinolysis, are considered significant pathogenetic events. Antithrombin III (ATIII), the main physiological serine protease inhibitor, has a critical role in the regulation of hemostasis. 29 patients with post necrotic cirrhosis undergoing liver transplantation were randomized to receive or not ATIII replacement therapy before the induction of anaesthesia and thereafter throughout surgery. Activation of both coagulation and fibrinolysis (increase of thrombin-antithrombin complexes, fibrin and fibrinogen degradation products) were demonstrated in both groups. Blood loss and transfusion requirements were not affected by ATIII administration.", "During liver transplantation (LT), profound activation of the fibrinolytic system can contribute significantly to perioperative bleeding. Prophylactic administration of antifibrinolytic agents has been shown to reduce blood loss and the need for allogeneic transfusion in these conditions.\n This prospective randomized trial included 51 cirrhotic patients undergoing LT. Patients were randomly assigned to receive either 280 mg of aprotinin (AP) followed by 70 mg per hour or 40 mg per kg tranexamic acid (TA) followed by 40 mg per kg per hour, administered from the end of the anhepatic phase until 2 hours after reperfusion of the graft, and the effects on blood loss and red blood cell (RBC) transfusion requirements were compared. Transfusion policy was standardized in all patients. In addition, the biological effects of the two drugs, as assessed by coagulation and fibrinolytic markers obtained during surgery, were evaluated in a subgroup of patients from each treatment group and compared with an historical control group that did not receive antifibrinolytic drugs.\n There was no significant difference between the two groups in perioperative blood losses (AP, 6200 [4620-8735] mL; TA, 5945 [4495-8527] mL; median [range]) or in RBC transfusions requirements (AP, 9 [6.75-15.25] units; TA, 10 [6.5-13.5] units). Inhibition of fibrinolysis was observed with both drugs compared with the control group. Coagulation appeared to be activated more with AP, however, whereas fibrinolysis was inhibited more by TA.\n Blood losses and RBC transfusion requirements were comparable regardless of the drug administered. TA may be as valuable as AP for controlling fibrinolysis in LT." ]

[ "2223679" ]

[ "Idiopathic thrombocytopenic purpura in pregnancy: a randomized trial on the effect of antenatal low dose corticosteroids on neonatal platelet count." ]

[ "To determine the efficacy of antenatal low dose oral betamethasone in preventing neonatal thrombocytopenia and/or bleeding in infants of mothers with idiopathic thrombocytopenic purpura (ITP).\n Hospital department of obstetrics and gynaecology, referral centre.\n 41 pregnancies in 38 women were randomized. The results of 13 pregnancies were considered non-assessable. The final analysis involved 14 in the betamethasone group and 14 in the non-treatment group. All fulfilled the criteria for ITP.\n The treated group received 1.5 mg betamethasone orally per day, from day 259 till day 273 and 1 mg from day 273 till delivery.\n Effects of treatment were assessed in terms of maternal platelet counts after the first trimester and neonatal platelet counts at birth and the first week of life and neonatal bleeding episodes.\n There were no significant differences in neonatal platelet counts at birth. Two infants in the betamethasone group and one in the untreated group had a severe thrombocytopenia either at birth or during the first week of life (less than 50 x 10(9)/l). Seven infants in the betamethasone group and six in the non-treatment group had a mild thrombocytopenia. The overall frequency of neonatal thrombocytopenia was similar: 64% in the betamethasone group and 57% in the untreated group (95% CI of the true difference: -43.5% to +29.5%). There was also no significant difference in neonatal bleeding episodes.\n Low-dose betamethasone in pregnant women with ITP does not prevent thrombocytopenia or bleeding in their newborn infants." ]

[ "11130385", "9196769", "9182474", "11528574", "14604928", "12235450", "15227617" ]

[ "Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study. Malarone International Study Team.", "Side effects of mefloquine prophylaxis for malaria: an independent randomized controlled trial.", "Mefloquine compared with doxycycline for the prophylaxis of malaria in Indonesian soldiers. A randomized, double-blind, placebo-controlled trial.", "Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double-blind study.", "Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study.", "Atovaquone plus chloroguanide versus mefloquine for malaria prophylaxis: a focus on neuropsychiatric adverse events.", "Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in nonimmune pediatric travelers: results of an international, randomized, open-label study." ]

[ "Chloroquine plus proguanil is widely used for malaria chemoprophylaxis despite low effectiveness in areas where multidrug-resistant malaria occurs. Studies have shown that atovaquone and proguanil hydrochloride is safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but little is known about non-immune travellers.\n In a double-blind equivalence trial, 1083 participants travelling to a malaria-endemic area were randomly assigned to two treatment groups: atovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroquine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by telephone 7 and 60 days after travel and at a clinic at 28 days. Serum samples were tested for antibodies to a malaria circumsporozoite protein. Blood and serum samples of participants with a potential malaria diagnosis were tested in a reference laboratory.\n 7 days after travel, at least one adverse event was reported by 311 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-proguanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse events of moderate or severe intensity (37 [7%] vs 56 [11%], p=0.05). There were fewer treatment-related adverse events that caused prophylaxis to be discontinued in the atovaquone-proguanil group than in the chloroquine-proguanil group (one [0.2%] vs ten [2%], p=0.015).\n Overall the two preparations were similarly tolerated. However, significantly fewer adverse gastrointestinal events were observed in the atovaquone-proguanil group in than in the chloroquine-proguanil group.", "A prospective randomized double-'blind' trial was undertaken during a military exercise in East Africa to determine whether there was a significant difference in the incidence of side effects experienced by soldiers taking mefloquine 250 mg weekly compared with those taking chloroquine 300 mg weekly and proguanil 200 mg daily as chemoprophylaxis for malaria. Subject to their informed voluntary consent, male soldiers who were not aviators were included in the study. Identical questionnaires were completed voluntarily at the end of 2 and 8 weeks. Symptoms were classified by nature into-'all', 'neuropsychological', 'enteric' and 'other', and by severity into 'severe' and 'very severe'. The proportions of respondents experiencing side effects were compared to seek statistically significant differences between the chemoprophylactic groups. Questionnaire 1 was completed after 2 weeks by 183 of 317 subjects (58%) randomly assigned mefloquine and by 176 of 307 subjects (57%) randomly assigned chloroquine-proguanil. The incidence of putative side effects was not significantly different between the groups (71/183 vs. 70/176), odds ratio 0.96 (95% confidence interval [CI] 0.63 to 1.47). Questionnaire 2 was completed after 8 weeks by 145 of 317 subjects (46%) randomly assigned mefloquine and by 142 of 307 subjects (46%) randomly assigned chloroquine-proguanil. The incidence of putative side effects was still not significantly different between the groups (95/145 vs. 103/142), odds ratio 0.72 (95% CI 0.43 to 1.19). None of the subjects developed a serious neuropsychological reaction. Among respondents, 12.8% and 38% admitted lack of full compliance at 2 and 8 weeks, respectively. Exclusion of these subjects during a secondary analysis did not affect the results. None of the subjects developed malaria in the 12 months following return to the UK. Subject to the limitations of a response rate that was smaller than desired and the fact that the study was conducted in fit male military personnel, these results support evidence which indicates that mefloquine is no more toxic than chloroquine-proguanil.", "Mefloquine and doxycycline are the two drugs recommended for prophylaxis of malaria for visitors to areas where Plasmodium falciparum is resistant to chloroquine.\n To compare the efficacy and tolerability of mefloquine with those of doxycycline as prophylaxis for malaria.\n Randomized, double-blind, placebo-controlled field trial of chemoprophylaxis of malaria.\n Northeastern Irian Jaya, Indonesia.\n 204 Indonesian soldiers.\n After radical curative treatment, participants were randomly assigned to receive 100 mg of doxycycline per day and mefloquine placebo; 250 mg of mefloquine per week (preceded by a loading dose of 250 mg/d for 3 days) and doxycycline placebo; or placebos for both drugs. Prophylaxis lasted approximately 13 weeks.\n The primary end point for efficacy was the first occurrence of malaria, as documented by a positive malaria smear. Malaria smears were obtained weekly and when patients had symptoms suggesting malaria. Reported symptoms were recorded daily, and an exit study questionnaire was conducted.\n In the placebo group, 53 of 69 soldiers developed malaria (9.1 person-years), resulting in an attack rate of 5.8 cases per person-year (95% CI, 4.3 to 7.7 cases per person-year). Plasmodium falciparum accounted for 57% of cases, and P. vivax accounted for 43% of cases. No malaria occurred in the 68 soldiers (16.9 person-years) in the mefloquine group; thus, the protective efficacy of mefloquine was 100% (CI, 96% to 100%). In the doxycycline group, P. falciparum malaria occurred in 1 of 67 soldiers (16.0 person-years), yielding a protective efficacy of 99% (CI, 94% to 100%). Both drugs were very well tolerated.\n Mefloquine and doxycycline were both highly efficacious and well tolerated as prophylaxis of malaria in Indonesian soldiers.", "Concerns about the tolerability of mefloquine highlight the need for new drugs to prevent malaria. Atovaquone-proguanil (Malarone; GlaxoSmithKline) was safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but experience in nonimmune people is limited. In a randomized, double-blind study, nonimmune travelers received malaria prophylaxis with atovaquone-proguanil (493 subjects) or mefloquine (483 subjects). Information about adverse events (AEs) and potential episodes of malaria was obtained 7, 28, and 60 days after travel. AEs were reported by an equivalent proportion of subjects who had received atovaquone-proguanil or mefloquine (71.4% versus 67.3%; difference, 4.1%; 95% confidence interval, -1.71 to 9.9). Subjects who received atovaquone-proguanil had fewer treatment-related neuropsychiatric AEs (14% versus 29%; P=.001), fewer AEs of moderate or severe intensity (10% versus 19%; P=.001), and fewer AEs that caused prophylaxis to be discontinued (1.2% versus 5.0%; P=.001), compared with subjects who received melfoquine. No confirmed diagnoses of malaria occurred in either group. Atovaquone-proguanil was better tolerated than was mefloquine, and it was similarly effective for malaria prophylaxis in nonimmune travelers.", "To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers.\n Randomised, double blind, study with placebo run-in phase.\n Travel clinics in Switzerland, Germany, and Israel.\n Proportion of participants in each treatment arm with subjectively moderate or severe adverse events.\n 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil.\n A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%), followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P = 0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n = 19; 12%, 7% to 18% and n = 16; 11%, 6% to 15%, respectively), whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n = 11; 7%, 2% to 11% and n = 9; 6%, 2% to 10%, respectively: P = 0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in women (n = 56; 37%, 29% to 44% versus chloroquine and proguanil, n = 46; 30%, 23% to 37%; doxycycline, n = 36; 24%, 17% to 30%; and atovaquone and proguanil, n = 32; 20%, 13% to 26%: P = 0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n = 12; 8%, 4% to 13% versus doxycycline, n = 5; 3%, 1% to 6%; atovaquone and proguanil, n = 4; 2%, 0% to 5%; mefloquine, n = 2; 1%, 0% to 3%: P = 0.013).\n Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.", "We performed a prospective, double-blind, randomized study to compare the occurrence of neuropsychiatric adverse events and concentration impairment during prophylactic use of either mefloquine or atovaquone plus chloroguanide (INN, proguanil).\n Our potential study population consisted of all persons who were included in the MAL30010 trial at the Travel Clinic, Rotterdam, The Netherlands. All subjects were randomized to receive either active atovaquone (250 mg) plus chloroguanide (100 mg) daily plus a placebo for mefloquine weekly or active mefloquine (250 mg) weekly plus a placebo for atovaquone plus chloroguanide daily. Each subject was followed up from a baseline screening visit up to the index date, 7 days after he or she left the malaria-endemic area. We measured the interindividual and intraindividual changes in mood disturbance by means of the Dutch shortened Profile of Mood States and 3 domains of the Neurobehavioral Evaluation System, which included sustained attention, coding speed, and visuomotor accuracy between baseline and follow-up visit.\n The cohort consisted of 119 subjects with a mean age of 35 years. A significant deterioration in depression, anger, fatigue, vigor, and total mood disturbance domains occurred during use of mefloquine but not during use of atovaquone plus chloroguanide. Stratification for sex showed between-treatment differences in female patients but not in male patients. In both treatment groups, sustained attention deteriorated after travel, especially with increased duration of stay.\n Prophylactic use of mefloquine was associated with significantly higher scores on scales for depression, anger, and fatigue and lower scores for vigor than prophylactic use of atovaquone plus chloroguanide.", "Atovaquone-proguanil has been shown to be effective and well tolerated for malaria prophylaxis in residents of countries of endemicity and in nonimmune adult travelers, but data about traveling children are limited. In a randomized, open-label, multicenter prophylaxis trial, 221 nonimmune pediatric travelers (age, 2-17 years) received either atovaquone-proguanil or chloroquine-proguanil. Safety and clinical outcome were evaluated 7, 28, and 60 days after travel. By posttravel day 7, a total of 39 (35%) of 110 atovaquone-proguanil and 41 (37%) of 111 chloroquine-proguanil recipients reported > or =1 adverse event. The data indicate that, over the course of treatment, fewer atovaquone-proguanil recipients had treatment-related adverse events (8% vs. 14%), including gastrointestinal complaints (5% vs. 10%). Two subjects discontinued prophylaxis because of drug-related adverse events; both had received chloroquine-proguanil. Observed compliance with prophylaxis was similar before and during travel, but it was higher for atovaquone-proguanil in the posttravel period. No study participant developed malaria. Atovaquone-proguanil was well tolerated and is an important addition to the limited arsenal of prophylactic agents available to children." ]

[ "8141537", "18334461", "8749210", "7009090", "8436235", "6722002", "14718419", "9562277", "3671224", "17971007", "15656462", "7567488" ]

[ "Influence of occlusive and impregnated gauze dressings on incisional healing: a prospective, randomized, controlled study.", "Prospective evaluation of occlusive hydrocolloid dressing versus conventional gauze dressing regarding the healing effect after abdominal operations: randomized controlled trial.", "To dress or not to dress surgical wounds? Patients' attitudes to wound care after major abdominal operations.", "[Transparent adhesive tape as postoperative dressing. Randomized, clinical study for comparison with a conventional dressing technic].", "Wound dressing in major head and neck cancer surgery: a prospective randomized study of gauze dressing vs sterile vaseline ointment.", "Tegadern versus gauze dressing in breast surgery.", "Effect of three wound dressings on infection, healing comfort, and cost in patients with sternotomy wounds: a randomized trial.", "Effects of occlusive and conventional gauze dressings on incisional healing after abdominal operations.", "Exposure of the wound--a safe economy in the NHS.", "Moist wound healing compared with standard care of treatment of primary closed vascular surgical wounds: a prospective randomized controlled study.", "Choice of dressing has a major impact on blistering and healing outcomes in orthopaedic patients.", "A comparison of three wound dressings in patients undergoing heart surgery." ]

[ "After elective surgery, 28 patients with 40 wounds were enrolled in a controlled clinical study to assess the effects of two different dressings on incisional healing. Patients served as their own control with one-half of each incision covered with an impregnated gauze (Xeroform) and the other half of the incision covered with a thin occlusive hydrocolloid dressing (DuoDerm Extra Thin CGF). All wounds were evaluated 2 to 3 days, 7 to 10 days, 4 weeks, and 7 months postoperatively. None of the incisions segments showed any evidence of infection. At the time of suture removal, the hydrocolloid dressing's ability to contain exudate, protect the wound, and facilitate mobility and personal hygiene were rated higher compared with the gauze-type dressing (p < 0.001, for all variables). At the 4-week visit, both the patient and the surgeon rated the scar segments covered with the hydrocolloid dressing better with respect to color, evenness, and suppleness (p < or = 0.04, for all variables). These differences were no longer apparent 7 months after surgery.", "To compare occlusive hydrocolloid dressing (OHD; Karayahesive) and gauze dressing (GD) with regard to the cost and incidence of wound infection after abdominal surgery.\n A total of 134 patients who underwent incisions were randomized to have their wounds dressed with either OHD or GD. OHD was left on until the sutures were removed, and GD was changed everyday postoperatively. The cost calculations represent the number of dressings required for each treatment group as determined by the frequency of required dressing changes and cost per dressing.\n There were no differences between the groups regarding the need for dressings to be changed or the incidence of infection. OHD was less expensive and complicated than GD, which needed to be changed everyday (p < 0.0001).\n The results suggest that OHD is less expensive to use than GD, and the risk of wound infection is not increased compared to GD.", "To find out what patients' attitudes were to wound care after abdominal operations to ensure that patients' own views were not violated by introducing a new method of wound care.\n Randomised study.\n University hospital, Sweden.\n 68 consecutive patients operated for benign gastrointestinal disease.\n Patients were randomised to have their abdominal wounds dressed or exposed. On their last day in hospital their attitudes were assessed by visual analogue score and questionnaire.\n Attitudes to wound care.\n There were no differences between the two groups in any of the variables studied. The visual analogue scores for postoperative pain were higher than had been anticipated.\n Most patients do not mind whether their wounds are covered with a dressing or not after abdominal operations.", "To evaluate the effect of a thin, transparent, adhesive and elastic polyurethane drape permeable only to gas and water vapor molecules but not to bacteria in comparison to a conventional drape for postoperative dressings, a randomized trial was conducted in 90 male and female patients. 44 patients had the transparent adhesive drape and 46 a conventional dressing. Both groups were reasonably well matched according to age, sex, height, weight and type of operation. There was no difference in healing of skin wounds. But reddening around the stitches was seen more often in patients with the conventional dressing than in those with the polyurethane drape (p less than 0.05). Surprisingly, most of the patients with the transparent drape (42 of 44) accepted it. The transparent adhesive drape was found to be much less expensive than the conventional dressing.", "A total of 207 patients were randomized in a prospective comparative study of standard gauze dressing vs sterile vaseline ointment. 179 patients were evaluable. All patients received antimicrobial prophylaxis. The two groups (86 standard and 93 vaseline) were comparable as far as age (mean, 57 yr; range, 21-84), genders (155 males/24 females), weight (mean, 66 kg; range, 40-69), type of surgery, previous or concomitant anticancer treatment. Severity of surgery was identical, as was the severity of cancer, in the two groups. Wound infection within 20 days of surgery occurred in 31.2% (29/93) of the vaseline group and 24.4% (21/86) in the standard group (NSS). Bacteremia occurred in three patients from the vaseline group and in four patients from the standard group. Bronchopneumonia occurred in 10 patients from the vaseline group and 14 patients in the standard group. The spectrum of microorganisms recovered was similar in the two groups. The need for antimicrobial treatment (empiric or for documented infections) within 20 days after surgery was 34.4% (32/93) in the vaseline group and 36.0% (31/86) in the standard group. The median delay to infection (range in days) in the vaseline group was 9 (5-15) for wound and 6 (1-12) for bronchopneumonia. For the standard group the corresponding delays were 8 (4-15) and 7 (2-19). Vaseline dressing was not associated with an increased risk of infection as compared to the standard gauze dressing.", "nan", "To compare three dressing types in terms of their ability to protect against infection and promote healing, patient comfort, and cost-effectiveness.\n Prospective, randomized controlled trial.\n Major metropolitan, academically affiliated, tertiary referral center.\n Seven hundred thirty-seven patients were randomized to receive a dry absorbent dressing (n = 243) [Primapore; Smith & Nephew; Sydney, NSW, Australia], a hydrocolloid dressing (n = 267) [Duoderm Thin ConvaTec; Mulgrave, VIC, Australia], or a hydroactive dressing (n = 227) [Opsite; Smith & Nephew] in the operating theater on skin closure.\n There was no difference in the rate of wound infection or wound healing between treatment groups. The Primapore dressing was the most comfortable and cost-effective dressing option for the sternotomy wound. Duoderm Thin dressings were associated with increased wound exudate (p < 0.001), poor dressing integrity (p < 0.001), more frequent dressing changes (p < 0.001), more discomfort with removal (p < 0.05), and increased cost (p < 0.001).\n In the context of no additional benefit for the prevention of wound infection or the rate of wound healing for any of the three dressing products examined, dry absorbent dressings are the most comfortable and cost-effective products for sternotomy wounds following cardiac surgery.", "To compare the effect of occlusive (Comfeel) and conventional (Mepore) dressings on the healing of incisional wounds after abdominal operations.\n Prospective randomised study.\n Laboratory and teaching hospital, Denmark.\n 73 patients who underwent clean operations requiring incisions longer than 5 cm between August 1993 and August 1995 were randomised to have their wounds dressed with either Comfeel or Mepore.\n Comfeel was left on until the sutures were removed, and Mepore was removed 2 days postoperatively.\n Infection, adherence, leakage, and cosmetic appearance three months later.\n 36 patients were randomised to have Comfeel and 37 to have Mepore. 29 patients were withdrawn from the study (20 having Mepore and 9 having Comfeel) leaving 26, and 17 for analysis, respectively. Wound infections developed in 1 patient in the Comfeel group and 5 in the Mepores group (p = 0.2). There were no differences between the groups regarding the need for dressings to be changed, the incidence of leakage, or loosening of the dressing from the skin. Comfeel adhered securely to the skin and remained more or less transparent until sutures were removed. It remained totally transparent in 23 (64%), and no dressing became totally opaque. There were no differences in cosmetic appearance after three months. We had the impression that patients who had Comfeel were more comfortable and found it easier to mobilise and carry out their daily activities.\n Occlusive dressings stay in place and stay transparent, and do not increase the risk of wound infection. They may even be more comfortable. they are a reasonable alternative to conventional dressings.", "nan", "This study was a randomized-controlled trial comparing the standard type of dry dressing, Mepore, with moist wound healing, using a hydrofiber dressing, Aquacel, in primary closed wounds after vascular surgery. The endpoints were patient comfort, cost-effectiveness, infections, wound complications, and length of hospital stay. One hundred and sixty patients were randomized to receive either Mepore or Aquacel dressing. There was no significant difference in patient comfort between the two groups, but a higher cost in the Aquacel group despite significantly fewer changes of dressings in these patients. No difference in the infection rate (13% vs. 11%, p=0.73), length of hospital stay, or wound complications was noted between the two groups. We conclude that although the Aquacel dressing needed significantly fewer changes than the conventional dressing, this did not influence the patient comfort. Moreover, the traditional dressing scheme was significantly less expensive.", "To investigate the effect of three postoperative dressings on orthopaedic wound healing.\n Three hundred orthopaedic patients were divided into three treatment groups and allocated to management with one of three dressings: Primapore, Tegaderm with pad, and OpSite Post-Op. Staff completed a questionnaire to evaluate the wound progression. Outcome measures were the presence of infection, blistering and the number of dressing changes required.\n There was a significantly lower incidence of blistering with OpSite Post-Op (6%) than Tegaderm with pad (16%) and Primapore (24%) (p<0.001). Patients in the OpSite Post-Op group had the lowest exudate levels.\n Dressings that employ a clear film and have a high moisture vapour transmission rate have been shown to reduce both the rate of blistering and wound discharge. The additional expense inherent in using such dressings may, in reality, prove cost-effective because of the reduced need for dressings changes and the subsequent earlier discharge of these patients from hospital with an uncomplicated wound.", "Two hundred fifty patients undergoing heart surgery were randomized in a prospective comparative study of a semiocclusive hydroactive wound dressing, an occlusive hydrocolloid dressing, and a conventional absorbent dressing. The wounds were evaluated during the 4 weeks after surgery. Color photographs were used for a blind evaluation of wound healing. The conventional absorbent dressing was more effective in wound healing, compared with the hydroactive dressing. Further, there were fewer skin changes and less redness in the wounds with the conventional dressing than with the hydroactive dressing; the differences were not significant with the hydrocolloid dressing. The conventional dressing was less painful to remove than the hydroactive and hydrocolloid dressings. More frequent dressing changes, however, were needed when using the conventional dressing. Despite this, it was the least expensive alternative." ]

[ "9443139", "20426604", "18304848", "11895532" ]

[ "Labor pain is reduced by massage therapy.", "Comparison between massage and music therapies to relieve the severity of labor pain.", "Massage or music for pain relief in labour: a pilot randomised placebo controlled trial.", "Effects of massage on pain and anxiety during labour: a randomized controlled trial in Taiwan." ]

[ "Twenty-eight women were recruited from prenatal classes and randomly assigned to receive massage in addition to coaching in breathing from their partners during labor, or to receive coaching in breathing alone (a technique learned during prenatal classes). The massaged mothers reported a decrease in depressed mood, anxiety and pain, and showed less agitated activity and anxiety and more positive affect following the first massage during labor. In addition, the massaged mothers had significantly shorter labors, a shorter hospital stay and less postpartum depression.", "During labor, women experience a high level of intense, stressful and steady pain that may negatively affect both mothers and neonates. Painkillers have previously been used for childbearing women, but nowadays, owing to some well-known limitations and serious side effects, nonpharmacologic methods such as massage and music therapies are being broadly recommended. The present clinical trial was conducted to compare the effects of massage and music therapies on the severity of labor pain in the Ilam province of western Iran.\n Overall, 101 primigravidae who were hospitalized for vaginal delivery were recruited and randomly stratified into two groups of either massage (n = 51) or music (n = 50) therapies. Pain was measured using the visual analog scale and the two groups were compared in terms of pain severity before and after the interventions.\n Mothers in the massage therapy group had a lower level of pain compared with those in the music therapy group (p = 0.009). A significant difference was observed between the two groups in terms of pain severity after intervention (p = 0.01). Agonizing, or most severe, labor pain was significantly relieved after massage therapy (p = 0.001).\n Massage therapy was an effective method for reducing and relieving labor pain compared with music therapy and can be clinically recommended as an alternative, safe and affordable method of pain relief where using either pharmacological or nonpharmacological methods are optional.", "Research on massage therapy for maternal pain and anxiety in labour is currently limited to four small trials. Each used different massage techniques, at different frequencies and durations, and relaxation techniques were included in three trials. Given the need to investigate massage interventions that complement maternal neurophysiological adaptations to labour and birth pain(s), we designed a pilot randomised controlled trial (RCT) to test the effects of a massage programme practised during physiological changes in pain threshold, from late pregnancy to birth, on women's reported pain, measured by a visual analogue scale (VAS) at 90 min following birth. To control for the potential bias of the possible effects of support offered within preparation for the intervention group, the study included 3 arms--intervention (massage programme with relaxation techniques), placebo (music with relaxation techniques) and control (usual care). The placebo offered a non-pharmacological coping strategy, to ensure that use of massage was the only difference between intervention and placebo groups. There was a trend towards slightly lower mean pain scores in the intervention group but these differences were not statistically significant. No differences were found in use of pharmacological analgesia, need for augmentation or mode of delivery. There was a trend towards more positive views of labour preparedness and sense of control in the intervention and placebo groups, compared with the control group. These findings suggest that regular massage with relaxation techniques from late pregnancy to birth is an acceptable coping strategy that merits a large trial with sufficient power to detect differences in reported pain as a primary outcome measure.", "To investigate the effects of massage on pain reaction and anxiety during labour.\n Labour pain is a challenging issue for nurses designing intervention protocols. Massage is an ancient technique that has been widely employed during labour, however, relatively little study has been undertaken examining the effects of massage on women in labour.\n A randomized controlled study was conducted between September 1999 and January 2000. Sixty primiparous women expected to have a normal childbirth at a regional hospital in southern Taiwan were randomly assigned to either the experimental (n=30) or the control (n=30) group. The experimental group received massage intervention whereas the control group did not. The nurse-rated present behavioural intensity (PBI) was used as a measure of labour pain. Anxiety was measured with the visual analogue scale for anxiety (VASA). The intensity of pain and anxiety between the two groups was compared in the latent phase (cervix dilated 3-4 cm), active phase (5-7 cm) and transitional phase (8-10 cm).\n In both groups, there was a relatively steady increase in pain intensity and anxiety level as labour progressed. A t-test demonstrated that the experimental group had significantly lower pain reactions in the latent, active and transitional phases. Anxiety levels were only significantly different between the two groups in the latent phase. Twenty-six of the 30 (87%) experimental group subjects reported that massage was helpful, providing pain relief and psychological support during labour.\n Findings suggest that massage is a cost-effective nursing intervention that can decrease pain and anxiety during labour, and partners' participation in massage can positively influence the quality of women's birth experiences." ]

[ "17903919", "3354029", "18396107", "12865611", "17324738", "8352673", "9056614", "15731556" ]

[ "The effects of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure, cerebral and cardiac hemodynamics, and plasma nitric oxide levels in acute stroke.", "Effect of nimodipine on blood pressure in acute ischemic stroke in humans.", "Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial.", "A pilot randomized trial of induced blood pressure elevation: effects on function and focal perfusion in acute and subacute stroke.", "Lisinopril for the treatment of hypertension within the first 24 hours of acute ischemic stroke and follow-up.", "Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography.", "Perindopril reduces blood pressure but not cerebral blood flow in patients with recent cerebral ischemic stroke.", "Bendrofluazide fails to reduce elevated blood pressure levels in the immediate post-stroke period." ]

[ "High blood pressure in acute stroke is common and appears to be associated with a poor outcome. Lowering blood pressure might therefore improve outcome, provided that cerebral perfusion is not compromised. We assessed the effects of glyceryl trinitrate (GTN) on cerebral and systemic hemodynamic measures in acute stroke. Ninety patients with acute ischemic or hemorrhagic stroke were randomized within 72 hours of ictus to transdermal GTN given daily for 10 days (either 5 mg, 5 mg for 4 days then 10 mg, or 10 mg) or control. Twenty-four hour blood pressure monitoring, middle cerebral artery blood velocity, cardiac output, augmentation index, and plasma nitric oxide levels were each measured at baseline and then on days 1, 4, 5, and 10. The primary outcome was blood pressure on day 1. We found that GTN lowered mean peripheral arterial blood pressure on day 1 by 5.3% to 6.7% in a dose dependent manner as compared with control (mean, SD): control, 108.8 (15.1) mmHg; 5 mg, 102.5 (13.9) mmHg; 5/10 mg, 103.4 (14.9) mmHg; 10 mg, 101.5 (12.6) mmHg; (P = .005). Increasing the dose from 5 to 10 mg on day 5 resulted in an overall reduction in blood pressure of 11.4% as compared with leaving the dose at 5 mg (P = .006). GTN reduced peripheral pulse pressure, central aortic blood pressure, pulse pressure, and augmentation index on day 1. Middle cerebral artery blood velocity and pulsatility index in the affected hemisphere, cardiac output, systemic peripheral resistance, and plasma nitric oxide levels were not altered by GTN. Treatment with GTN was associated with headache: control 0 (0%), GTN 9 (15%) (P = .027); no negative effect on end-of-treatment death or deterioration, or 3 month death or dependency was discernable. GTN reduced peripheral blood pressure in a dose-dependent fashion in patients with acute stroke at day 1 and also reduced central blood pressure and augmentation index. In contrast, GTN did not alter middle cerebral artery blood velocity or pulsatility index in the affected hemispheres, suggesting that cerebral blood flow did not change. A trial assessing the effect of lowering blood pressure with GTN on safety and functional outcome in patients with acute stroke is now warranted.", "Nimodipine is currently under investigation for the treatment of acute stroke. Although relatively specific for the cerebrovasculature, acute reductions in blood pressure after a dose may adversely affect neurologic outcome. We studied 29 consecutive acute ischemic stroke patients treated with placebo (n = 9) or either 120 (n = 10) or 240 (n = 10) mg/day of nimodipine. Blood pressure was recorded before and 30 and 60 minutes after a dose for the first 8 days. Ten neurologic physicians were asked to predict the treatment group (placebo or drug) of randomly selected patients based on blood pressure results. Only those patients on 240 mg/day of nimodipine had significant decreases in blood pressure after a dose (p less than 0.001); however, these were minimal (average 10 mm Hg systolic). Only 26 of 48 treatment predictions (54%) were correct. At the studied doses, nimodipine has a minimal effect on blood pressure in the acute stroke period.", "There is much uncertainty about the effects of early lowering of elevated blood pressure (BP) after acute intracerebral haemorrhage (ICH). Our aim was to assess the safety and efficiency of this treatment, as a run-in phase to a larger trial.\n Patients who had acute spontaneous ICH diagnosed by CT within 6 h of onset, elevated systolic BP (150-220 mm Hg), and no definite indication or contraindication to treatment were randomly assigned to early intensive lowering of BP (target systolic BP 140 mm Hg; n=203) or standard guideline-based management of BP (target systolic BP 180 mm Hg; n=201). The primary efficacy endpoint was proportional change in haematoma volume at 24 h; secondary efficacy outcomes included other measurements of haematoma volume. Safety and clinical outcomes were assessed for up to 90 days. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00226096.\n Baseline characteristics of patients were similar between groups, but mean haematoma volumes were smaller in the guideline group (12.7 mL, SD 11.6) than in the intensive group (14.2 mL, SD 14.5). From randomisation to 1 h, mean systolic BP was 153 mm Hg in the intensive group and 167 mm Hg in the guideline group (difference 13.3 mm Hg, 95% CI 8.9-17.6 mm Hg; p<0.0001); from 1 h to 24 h, BP was 146 mm Hg in the intensive group and 157 mm Hg in the guideline group (10.8 mm Hg, 95% CI 7.7-13.9 mm Hg; p<0.0001). Mean proportional haematoma growth was 36.3% in the guideline group and 13.7% in the intensive group (difference 22.6%, 95% CI 0.6-44.5%; p=0.04) at 24 h. After adjustment for initial haematoma volume and time from onset to CT, median haematoma growth differed between the groups with p=0.06; the absolute difference in volume between groups was 1.7 mL (95% CI -0.5 to 3.9, p=0.13). Relative risk of haematoma growth >or=33% or >or=12.5 mL was 36% lower (95% CI 0-59%, p=0.05) in the intensive group than in the guideline group. The absolute risk reduction was 8% (95% CI -1.0 to 17%, p=0.05). Intensive BP-lowering treatment did not alter the risks of adverse events or secondary clinical outcomes at 90 days.\n Early intensive BP-lowering treatment is clinically feasible, well tolerated, and seems to reduce haematoma growth in ICH. A large randomised trial is needed to define the effects on clinical outcomes across a broad range of patients with ICH.\n National Health and Medical Research Council of Australia.", "Small, unrandomized studies have indicated that pharmacologically induced blood pressure elevation may improve function in ischemic stroke, presumably by improving blood flow to ischemic, but noninfarcted tissue (which may be indicated by diffusion-perfusion mismatch on MRI). We conducted a pilot, randomized trial to evaluate effects of pharmacologically induced blood pressure elevation on function and perfusion in acute stroke.\n Consecutive series of patients with large diffusion-perfusion mismatch were randomly assigned to induced blood pressure elevation ('treated' patients, n = 9) or conventional management ('untreated' patients, n = 6).\n There were no significant differences between groups at baseline. NIH Stroke Scale (NIHSS) scores were lower (better) in treated versus untreated patients at day 3 (mean 5.6 vs. 12.3; p = 0.01) and week 6-8 (mean 2.8 vs. 9.7; p < 0.04). Treated (but not untreated) patients showed significant improvement from day 1 to day 3 in NIHSS score (from mean 10.2 to 5.6; p < 0.002), cognitive score (from mean 58.7 to 27.9% errors; p < 0.002), and volume of hypoperfused tissue (mean 132 to 58 ml; p < 0.02). High Pearson correlations between the mean arterial pressure (MAP) and accuracy on daily cognitive tests indicated that functional changes were due to changes in MAP.\n Results warrant a full-scale, double-blind clinical trial to evaluate the efficacy and risk of induced blood pressure elevation in selective patients with acute/subacute stroke.\n Copyright 2003 S. Karger AG, Basel", "Hypertension immediately after acute ischemic stroke is associated with impaired morbidity and mortality, although there are few data on antihypertensive use immediately after ictus. This randomized, double-blinded, placebo-controlled, parallel-group study explored the hemodynamic effect and safety of oral lisinopril initiated within 24 h after an ictus.\n Forty hypertensive (systolic blood pressure [BP] >/=140 or diastolic BP >/=90 mm Hg) acute ischemic stroke patients (14 lacunar, 13 partial anterior, 7 total anterior, 6 posterior circulation infarct) were randomized to 5 mg of oral lisinopril (n = 18) or matching placebo (n = 22). Dose was increased to 10 mg (or 2 x placebo) on day 7 if casual systolic BP was >/=140 mm Hg and continued to day 14. After the initial dose, automated BP levels were monitored for 16 h. The BP levels and stroke outcome measures were assessed at day 14, and all patients were followed to day 90.\n At h 4 after the first dose, systolic/diastolic BP change was -20 +/- 21/-6 +/- 10 mm Hg (mean +/- SE) in the lisinopril group and 1 +/- 11/0 +/- 8 mmHg in the placebo group (group differences: systolic BP, P < .05; diastolic BP, P = .07). With a daily dosing regime, systolic BP, mean arterial pressure (MAP), diastolic BP, and pulse pressure (PP) were significantly lower in the lisinopril group compared to the placebo group at day 14 (P < .01). Neurologic and functional measures were similar between groups at follow-up.\n Lisinopril, even at small dosages, is well tolerated and an effective hypotensive agent after acute ischemic stroke, gradually reducing BP by 4 h after oral first-dose administration. Oral lisinopril is now being studied in a larger outcome-based trial in acute hypertensive stroke patients.", "To determine if previously hypertensive patients with acute ischemic stroke should be treated with antihypertensive medication in the immediate poststroke period.\n Randomized double-blind, placebo-controlled trial.\n Sixteen consecutive hypertensive patients (four men and 12 women; mean age, 66 years [age range, 46 to 83 years]) with middle cerebral artery infarction within 72 hours of onset and blood pressure between 170 and 220 mm Hg(systolic) and 95 and 120 mm Hg (diastolic).\n Placebo (n = 6), nicardipine hydrochloride (20 mg [n = 5]), captopril (12.5 mg [n = 3]), or clonidine hydrochloride (0.1 mg [n = 2]) given every 8 hours for 3 days.\n Decline in blood pressure, change in cerebral blood flow as measured by single photon emission computed tomography, and clinical change as determined by the National Institutes of Health Stroke Scale.\n Blood pressure fell significantly in both the drug-treated group as a whole and in those patients receiving placebo (P < .001). There was no difference in blood pressure levels between these two groups throughout the study period. Patients receiving nicardipine had a consistently lower pressure than the other groups. A significant negative relationship was noted between the maximum blood pressure fall and improvement in cerebral blood flow. There were four patients whose blood pressure dropped by more than 16% of the baseline value on any 24 hours in the first 3 days. All either failed to increase or actually decreased their cerebral blood flow to the affected area. Three of these patients were treated with nicardipine. There was no significant difference in clinical course between the placebo-and drug-treated groups as a whole.\n Hypertensive ischemic stroke patients with a moderate elevation of blood pressure in the first few days may not require antihypertensive therapy. Nicardipine and possibly other calcium channel blockers may cause an excessive fall in blood pressure and impair cerebral blood flow in these patients and should therefore be used with caution.", "The relationship between high blood pressure and the incidence of stroke is well established. Currently the effects of lowering blood pressure in patients with established cerebrovascular disease is undetermined, and there is continuing concern regarding the treatment of patients soon after a stroke event. Angiotensin-converting enzyme inhibitors maintain cerebral blood flow despite lowering blood pressure in patients with heart failure and otherwise uncomplicated hypertension. We tested the hypothesis that perindopril, an angiotensin-converting enzyme inhibitor with a gradual onset of action and a minimal first-dose hypotensive effect, lowers blood pressure without adversely affecting cerebral blood flow in patients 2 to 7 days after symptoms of cerebral infarction.\n Patients were randomized to receive 15 days of oral perindopril (4 mg) or placebo in a double-blind study. Blood pressure was monitored semiautomatically. Cerebral blood flow was calculated from internal carotid artery and vertebral Doppler ultrasound, supplemented by middle cerebral artery blood velocities.\n Twenty-four patients completed the protocol; four additional patients were withdrawn for reasons unrelated to treatment. Patients on perindopril had a placebo-corrected reduction in blood pressure of 19/11 mm Hg. Blood pressure remained reduced after 2 weeks of treatment. In contrast, total cerebral blood flow was unaffected by perindopril. Neurological symptoms improved similarly in both groups.\n Perindopril was well tolerated and effectively reduced blood pressure without reducing carotid territory blood flow in patients with symptoms of recent cerebral ischemia.", "Blood pressure (BP) levels, beat-to-beat blood pressure variability, dynamic cerebral autoregulation and cardiac baroreceptor sensitivity are frequently abnormal following acute stroke and are associated with an adverse short- and long-term prognosis. Thiazide diuretics are effective antihypertensive agents in preventing primary and secondary stroke, but their hypotensive and cerebral autoregulatory effects in the immediate post-stroke period have not been studied.\n Thirty-seven hypertensive neuroradiologically proven ischaemic stroke patients were randomized in a double-blind, placebo controlled, parallel group study to bendrofluazide 2.5 mg daily or matching placebo, within 96 h of stroke onset, for a 7-day period. Casual and non-invasive beat-to-beat arterial BP levels, cerebral blood flow velocity, ECG and transcutaneous carbon dioxide levels were measured within 70 +/- 20 h of cerebral infarction and again 7 days later. Dynamic cerebral autoregulatory indices, pulse interval, BP variability and cardiac baroreceptor sensitivity were also calculated.\n Small, non-significant falls were seen in casual and beat-to-beat BP levels over the 7-day period in both active and placebo-treated patients with no differences between treatments. No significant changes were seen in dynamic cerebral autoregulation or in cardiac baroreceptor sensitivity during the follow-up in either group.\n Following acute ischaemic stroke, the standard dose of bendrofluazide at 2.5 mg daily in this study sample did not lower systemic BP levels over the subsequent 7-day period. There was no evidence that bendrofluazide significantly altered cerebral autoregulation or improved cardiac baroreceptor sensitivity post-ictus. Bendrofluazide appears to be an ineffective hypotensive agent at the standard dosage in the initial post-stroke period.\n Copyright 2005 S. Karger AG, Basel." ]

[ "12365120", "11961377", "15863532", "11420821", "10804490", "3074776", "12066083", "3056499" ]

[ "Drainage at caesarean section--a randomised prospective study.", "Value of subcutaneous drainage system in obese females undergoing cesarean section using pfannenstiel incision.", "Subcutaneous tissue reapproximation, alone or in combination with drain, in obese women undergoing cesarean delivery.", "No benefit from post-caesarean wound drainage.", "Subcutaneous drain vs. suture in obese women undergoing cesarean delivery. A prospective, randomized trial.", "A controlled trial on wound drainage in caesarean section.", "Subcutaneous stitch closure versus subcutaneous drain to prevent wound disruption after cesarean delivery: a randomized clinical trial.", "Closed suction wound drainage and lower-segment caesarean section." ]

[ "To determine the efficacy of wound drainage at caesarean section with a view to reducing postoperative wound morbidity.\n King Edward VIII Hospital, Durban, South Africa.\n Four hundred and forty women undergoing emergency caesarean section using the transverse suprapubic incision were randomised to receive either drainage or non-drainage of the wound. Wound drains were removed 48 hours after surgery and patients were seen daily until the time of discharge from hospital. Wound inflammation, wound infection and duration of hospital stay were assessed in both groups.\n Seventy-two of the 440 patients (16.4%) developed wound morbidity ranging from induration, serous, sanguinous and purulent discharge to haematoma formation and wound dehiscence. Of the 217 patients who received drains, 37 showed evidence of wound morbidity (17.1%), as opposed to 35 of the 223 who were not drained (15.7%) (P = 0.701).\n No significant advantages could be demonstrated for routine drainage in terms of wound inflammation, wound infection, haematoma formation or duration of hospital stay.", "To determine whether closed subcutaneous drainage systems were efficacious in reducing the rate of wound breakdown of Pfannenstiel incision after cesarean section (CS) in obese females.\n Prospective controlled clinical trial.\n 118 obese pregnant females with a body mass index >32 undergoing CS were divided into two groups: group I (n = 78) with closed subcutaneous drainage system and group II (n = 40) without drainage system. Incision closure technique was standardized. Prophylactic antibiotics were given routinely to both groups.\n Primary outcomes were the incidence of wound breakdown in both groups together with rate of hematoma formation and occurrence of fever. Secondary outcomes were amount of fluid drained, need for redressing.\n Wound breakdown occurred in 9 cases in group I (11.5%), while it happened in 5 cases in group II (12.5%) (p > 0.05). Relative risk was 0.92 (95% CI 0.26-3.75). Hematoma formation was observed in only 1 case in the nondrainage group (group II). Fever was observed in 18 cases in group I (23.1%) in the first 24 h postoperative while in group II, 13 cases developed fever (32.5%) (p > 0.05). The need for redressing within the first 24 h was only in 2.5% of cases in group I while it was 17.9% in group II (p < 0.05).\n We found no significant benefit in using a subcutaneous drain as a prophylactic measure against wound breakdown in obese pregnant females undergoing CS as long as they received a prophylactic antibiotic.\n Copyright 2002 S. Karger AG, Basel", "To compare the efficacy of subcutaneous suture reapproximation alone with suture plus subcutaneous drain for the prevention of wound complications in obese women undergoing cesarean delivery.\n We conducted a multicenter randomized trial of women undergoing cesarean delivery. Consenting women with 4 cm or more of subcutaneous thickness were randomized to either subcutaneous suture closure alone (n = 149) or suture plus drain (n = 131). The drain was attached to bulb suction and removed at 72 hours or earlier if output was less than 30 mL/24 h. The primary study outcome was a composite wound morbidity rate (defined by any of the following: subcutaneous tissue dehiscence, seroma, hematoma, abscess, or fascial dehiscence).\n From April 2001 to July 2004, a total of 280 women were enrolled. Ninety-five percent of women (268/280) had a follow-up wound assessment. Both groups were similar with respect to age, race, parity, weight, cesarean indication, diabetes, steroid/antibiotic use, chorioamnionitis, and subcutaneous thickness. The composite wound morbidity rate was 17.4% (25/144) in the suture group and 22.7% (28/124) in the suture plus drain group (relative risk 1.3, 95% confidence interval 0.8-2.1). Individual wound complication rates, including subcutaneous dehiscence (15.3% versus 21.8%), seroma (9.0% versus 10.6%), hematoma (2.2% versus 2.4%), abscess (0.7% versus 3.3%), fascial dehiscence (1.4% versus 1.7%), and hospital readmission for wound complications (3.5% versus 6.6%), were similar (P > .05) between women treated with suture alone and those treated with suture plus drain, respectively.\n The additional use of a subcutaneous drain along with a standard subcutaneous suture reapproximation technique is not effective for the prevention of wound complications in obese women undergoing cesarean delivery.", "A prospective randomized controlled trial to determine the benefit of caesarean wound drainage in 305 low-risk pregnant women.\n Pregnant women at low risk of haemorrhage undergoing caesarean section in the Department of Obstetrics, University Hospital, Zurich, between June 1998 and July 1999 were randomised after informed consent into a no-suction group (n = 154) without post-caesarean wound drainage versus a control group with wound drainage (subfascial and subcutaneous) (n = 151). Outcome measures were perioperative decrease in haemoglobin (Hb), postpartum fever (> 38.5 degrees C for > 2 days), sonographic haematoma and other complications requiring revision, cumulative opiate dose adjusted to body weight, length of hospitalisation and operation time.\n 305 patients completed the study. Decrease in Hb and the rates of fever, haematoma and revision were similar in both groups. However, cumulative opiate dose was lower in the no-suction group (4.5 +/- 1.8 vs 2.8 +/- 1.4 injections, p = 0.0001), and hospital stay was shorter (6.5 +/- 2.4 vs 7.4 +/- 2.8 days, p = 0.0058), as was operation time (32.7 +/- 11.3 v 36.1 +/- 10.5 min; p = 0.0071).\n Routine post-caesarean wound drainage is not only useless but cost-ineffective. In the light of our results, wound drainage may be questioned and should be analysed generally.", "To determine if subcutaneous drain or closure of the subcutaneous layer decreases the incidence of wound complications in obese women undergoing cesarean delivery.\n Seventy-six obese women undergoing cesarean delivery and with at least 2 cm of subcutaneous fat were randomized to one of three groups: group 1 had suture closure of the subcutaneous tissue, group 2 had placement of a subcutaneous closed suction drain, and group 3 had neither suture closure nor drainage.\n Wound separation occurred in 12 (15.8%), seroma in 5 (6.6%) and infection in 3 (4%). There were no reports of wound hematoma. The overall incidence of any wound complication (infection, separation, seroma, hematoma) was higher in obese women who received neither subcutaneous suture nor drain as compared to obese women who received either subcutaneous suture closure or subcutaneous drain. The incidence of major wound complications (infection or separation) was also higher in obese women who received neither subcutaneous suture or drain compared to obese women who received either subcutaneous suture closure or subcutaneous drain.\n The use of closed suction drainage in the subcutaneous space may reduce the incidence of postoperative wound complications in obese women who have at least 2 cm of subcutaneous fat and undergo cesarean delivery.", "A randomized controlled trial was carried out to investigate the influence of drainage on wound infection following Caesarean section. The incidence of clinical wound infection was significantly reduced if a Redivac suction drain was placed beneath the rectus sheath. Subcutaneous corrugated drains were found to offer no advantage. Three different degrees of postoperative pyrexia are examined for their predictive value for the development of wound sepsis. The influence of duration of amnion rupture and the number of vaginal examinations in labour on the postoperative incidence of wound infection and pyrexia are examined.", "The purpose of this study was to compare a subcutaneous stitch closure and subcutaneous drain placement for the risk of wound disruption after cesarean delivery.\n This was a prospective randomized clinical trial that evaluated subcutaneous stitch closure, placement of a subcutaneous drain, or no closure for subsequent wound disruption risk in women with subcutaneous depth at >or=2 cm.\n The maternal demographics and intrapartum risk factors for postoperative wound disruptions were similar among the 964 study subjects, who were divided into 3 groups. Wound disruptions that required opening of the wound, irrigation, debridement, packing, and/or secondary delayed closure occurred in 9.7% of the women with no closure, 10.4% of the women in the stitch closure group, and 10.3% of the women in the closed drain group (P =.834).\n There appears to be no difference in the subsequent risk of wound complications when no closure of the subcutaneous tissue layers occurs versus suture closure or a closed drainage system.", "In a randomized controlled study of wound suction drainage after transverse suprapubic incision for lower-segment caesarean section no significant advantages could be demonstrated for routine drainage in terms of wound infection, haematoma formation, duration of hospital stay or analgesic requirements." ]

[ "9781529", "8726542" ]

[ "A multicenter trial of ropinirole as adjunct treatment for Parkinson's disease. Ropinirole Study Group.", "Ropinirole in the treatment of levodopa-induced motor fluctuations in patients with Parkinson's disease." ]

[ "To evaluate the nonergot dopamine agonist ropinirole as an adjunct to L-dopa in a randomized, double-blind trial in PD patients with motor fluctuations.\n L-dopa in the treatment of PD is associated with motor fluctuations, dyskinesia, and other adverse effects. The use of dopamine agonists in the treatment of PD delays recourse to L-dopa and thus delays the possibility of adverse effect onset.\n Ropinirole (n = 95) or placebo (n = 54) was added to L-dopa, and L-dopa was then reduced in a planned manner during the 6-month trial.\n A significantly greater number of ropinirole patients were able to achieve a 20% or greater reduction in both L-dopa dose and in percent time spent \"off\" compared with placebo (35.0% versus 13.0%; p = 0.003). The mean daily L-dopa dose was reduced significantly with ropinirole treatment (242 mg versus 51 mg; p < 0.001) as was the percent awake time spent \"off\" (11.7% versus 5.1%; p = 0.039). There was no difference in the percent of patients who withdrew because of adverse effects (15.8% on ropinirole versus 16.7% on placebo).\n Ropinirole permits a reduction in L-dopa dose with enhanced clinical benefit for PD patients with motor fluctuations.", "Forty-six patients with Parkinson's disease experiencing motor fluctuations and not optimally controlled on levodopa received as adjunct therapy a new nonergoline dopamine agonist, ropinirole, in a 3-month randomized placebo-controlled trial. Ropinirole significantly reduced the duration of off periods as assessed by self-scoring diary cards. There were more nonserious dopaminergic adverse events in the ropinirole group. More patients withdrew because of adverse events or insufficient therapeutic effect in the placebo group. Ropinirole has beneficial adjuvant effects in parkinsonian patients with moderate motor disability and motor fluctuations." ]

[ "17681825", "3201506" ]

[ "Subtle cerebral damage after shunting vs non shunting during carotid endarterectomy.", "Carotid endarterectomy: to shunt or not to shunt." ]

[ "To compare the extent of subtle cerebral damage (SCD) in patients undergoing carotid endarterectomy with or without shunt placement.\n Prospective, randomised study.\n We assessed a consecutive series of 96 patients undergoing endarterectomy for severe unilateral left carotid stenosis who had been randomly assigned to receive a shunt (48) or not (48). Eligibility criteria included age up to 80 years and Mini-Mental State Examination score >24 points. Patients underwent neuropsychological testing before surgery. Serum concentrations of S100 protein, neuron-specific enolase (NSE) and interleukin-6 (IL-6) were measured intraoperatively before and after carotid clamping. Finally, each patient underwent neuropsychological testing 3 weeks after surgery.\n Patients with and without shunt had similar serum concentrations of S100 protein, NSE and IL-6 as well as similar neuropsychological test scores, all p>0.05.\n There was no difference in subtle cerebral damage between patients randomized to receive a shunt or not.", "Because of controversies in the cerebrovascular literature regarding the use of an intraluminal shunt in carotid endarterectomy, we report a randomized prospective study of 118 consecutive symptomatic patients receiving surgery within a single neurosurgical practice. Over 4 years, 138 carotid endarterectomies were performed in the 118 patients, 63 operations with intraluminal shunting and 75 without. Standard rationale for surgery included ipsilateral cerebral infarction in 38% of the operations and ipsilateral transient ischemic attacks in 36%. Unilateral angiographic stenosis of greater than 90% was seen in 58% of the operations; there were no ipsilateral occlusions. Surgery was performed under general anesthesia with barbiturate induction and mild blood pressure elevation. The 30-day complication rate included a mortality rate of 0.7% with a 5.1% incidence of postoperative neurologic deficit and a 1.4% rate of myocardial infarction. In the 24 hours after surgery there were no cerebral infarctions in the shunted group and six in the unshunted group. This 8% rate in the unshunted group compared with 0% in the shunted group was significant at p = 0.023 with a power of 0.95 by Fisher's exact test and chi 2 analysis. This suggests that in our neurosurgical practice (resident training program) the use of an intraluminal shunt during carotid endarterectomy significantly reduces the risk of intraoperative neurologic deficit without increasing the incidence of other complications." ]

[ "18547500" ]

[ "Absorbent products for urinary/faecal incontinence: a comparative evaluation of key product designs." ]

[ "To compare the performance and cost-effectiveness of the key absorbent product designs to provide a more solid basis for guiding selection and purchase. Also to carry out the first stage in the development of a quality of life (QoL) instrument for measuring the impact of absorbent product use on users' lives.\n Three clinical trials focused on the three biggest market sectors. Each trial had a similar crossover design in which each participant tested all products within their group in random order. SETTING, PARTICIPANTS AND INTERVENTIONS: In Trial 1, 85 women with light urinary incontinence living in the community tested three products from each of the four design categories available (total of 12 test products): disposable inserts (pads); menstrual pads; washable pants with integral pad; and washable inserts. In Trial 2a, 85 moderate/heavily incontinent adults (urinary or urinary/faecal) living in the community (49 men and 36 women) tested three (or two) products from each of the five design categories available (total of 14 test products): disposable inserts (with mesh pants); disposable diapers (nappies); disposable pull-ups (similar to toddlers' trainer pants); disposable T-shaped diapers (nappies with waist-band); and washable diapers. All products were provided in a daytime and a (mostly more absorbent) night-time variant. In these first two trials, the test products were selected on the basis of data from pilot studies. In Trial 2b, 100 moderate/heavily incontinent adults (urinary or urinary/faecal) living in 10 nursing homes (27 men and 73 women) evaluated one product from each of the four disposable design categories from Trial 2a. Products were selected on the basis of product performance in Trial 2a and, again, day time and night-time variants were provided. The first phase of developing a QoL tool for measuring the impact of using different pad designs was carried out by interviewing participants from Trials 1 and 2a.\n Product performance (e.g. comfort, discreetness) was characterised using a weekly validated questionnaire. A daily pad change and leakage diary was used to record severity of leakage, numbers of laundry items and pads. Skin health changes were recorded weekly. At a final interview preferences were ranked, acceptability of each design recorded, and overall opinion marked on a visual analogue scale (VAS) of 0-100 points. This VAS score was used to estimate cost-effectiveness. In addition, a timed pad changing exercise was conducted with 10 women from Trial 2b to determine any differences between product designs.\n Disposable inserts are currently the mainstay of management for lightly incontinent women (Trial 1) and they were better for leakage and other variables (but not discreetness) and better overall than the other three designs. However, some women preferred menstrual pads (6/85) or washable pants (13/85), both of which are cheaper to use. Washable inserts were worse both overall and for leakage than the other three designs (72/85 found them unacceptable). For disposable inserts and disposable diapers, findings from the community (Trial 2a) and nursing home trials (Trial 2b) were broadly similar. Leakage performance of disposable inserts was worse than that of the other designs for day and night. Pull-ups were preferred over inserts for the daytime. The new T-shaped diaper was not better overall than the traditional disposable one. However, there were important differences in performance and preference findings for men and women from both trials. Pull-ups (the most expensive) were better overall than the other designs for women during the day and for community-dwelling women during the night. Although disposable diapers were better for leakage than disposable inserts (the cheapest), women did not prefer them (except in nursing homes at night), but for men the diapers were better both overall and for leakage and were the most cost-effective design. No firm conclusions could be drawn about the performance of designs for faecal incontinence. Nursing home carers found pull-ups and inserts easier to apply (in the standing position) and quicker (in the pad change experiment) than the diaper designs; the ability to stand was associated with preference for pull-ups or inserts. The T-shaped diaper was not easier or quicker to change than the diaper. The washable products (Trial 2a) gave diverse results: they were better for leakage at night, but were worse overall for daytime than the other designs. Three-quarters of the women (27/36) found them unacceptable, but nearly two-thirds of men (31/49) found them highly acceptable at night. Findings from the two community trials (Trials 1 and 2a) showed that there were many practical problems in dealing with washable products but, together with the less effective and less expensive products, such as menstrual pads, they were more acceptable at home (and, in the case of washables, at night). This suggests that cost-effective management may involve combining products by using more effective (for a given user) but more expensive designs (e.g. pull-ups) when out and less effective but less expensive designs when at home. The interviews examining the impact of pad use on QoL provided themes and domains that can be further developed into a tool for further evaluation of absorbent products.\n This study showed that there were significant and substantial differences between the designs of absorbent products and for moderate/heavy incontinence some designs are better for men/women than others. There was considerable individual variability in preferences and cost-effective management may best be achieved by allowing users to choose combinations of designs for different circumstances within a budget. Further research is needed into the feasibility of providing choice and combinations of designs to users, as well as into the development of more effective washables and of specifically male disposable products. QoL measurement tools are needed for users of absorbent products, as are clinical trials of designs for community-dwelling carer-dependent men and women with moderate/heavy incontinence." ]

[ "19853518", "17397702" ]

[ "Feasibility study of Transcutaneous Electrical Nerve Stimulation (TENS) for cancer bone pain.", "Transcutaneous electrical nerve stimulation vs. transcutaneous spinal electroanalgesia for chronic pain associated with breast cancer treatments." ]

[ "This multicenter study assessed the feasibility of conducting a phase III trial of transcutaneous electrical nerve stimulation (TENS) in patients with cancer bone pain recruited from palliative care services. Eligible patients received active and placebo TENS for 1 hour at site of pain in a randomized crossover design; median interval between applications 3 days. Responses assessed at 30 and 60 minutes included numerical and verbal ratings of pain at rest and on movement, and pain relief. Recruitment, tolerability, adverse events, and effectiveness of blinding were also evaluated. Twenty-four patients were randomised and 19 completed both applications. The intervention was well tolerated. Five patients withdrew: 3 due to deteriorating performance status, and 2 due to increased pain (1 each following active and placebo TENS). Confidence interval estimation around the differences in outcomes between active and placebo TENS suggests that TENS has the potential to decrease pain on movement more than pain on rest. Nine patients did not consider that a placebo was used; the remaining 10 correctly identified placebo TENS. Feasibility studies are important in palliative care prior to undertaking clinical trials. Our findings suggest that further work is required on recruitment strategies and refining the control arm before evaluating TENS in cancer bone pain.\n Cancer bone pain is common and severe, and partly mediated by hyperexcitability. Animal studies suggest that Transcutaneous Electrical Nerve Stimulation can reduce hyperalgesia. This study examined the feasibility of evaluating TENS in patients with cancer bone pain in order to optimize methods before a phase III trial.\n Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.", "Chronic pain associated with breast cancer treatment is becoming increasingly recognized. Patients with this condition can experience significant physical and psychological morbidity and may benefit from nonpharmacological interventions as part of a multidisciplinary team approach. We compared the effectiveness of transcutaneous electrical nerve stimulation (TENS), transcutaneous spinal electroanalgesia (TSE), and a placebo (sham TSE) in a randomized controlled trial. The study sample comprised 41 women with chronic pain following breast cancer treatment, and outcome measures included pain report, pain relief, pain interference, anxiety and depression, arm mobility, and analgesic consumption. There was little evidence to suggest that TENS or TSE were more effective than placebo. All three interventions had beneficial effects on both pain report and quality of life, a finding that may be due to either psychophysical improvements resulting from the personal interaction involved in the treatment or a placebo response. Although electrical stimulation appears to be well tolerated in this population, further research is needed to establish its effectiveness for chronic cancer treatment-related pain." ]

[ "10665626", "12523875", "1984763", "10867972", "8120960", "10846305", "10770458", "1728157", "8601548" ]

[ "Safety and tolerability of oral loading divalproex sodium in acutely manic bipolar patients.", "A comparison of the efficacy, safety, and tolerability of divalproex sodium and olanzapine in the treatment of bipolar disorder.", "Valproate in the treatment of acute mania. A placebo-controlled study.", "Carbamazepine and valproate monotherapy: feasibility, relative safety and efficacy, and therapeutic drug monitoring in manic disorder.", "Efficacy of divalproex vs lithium and placebo in the treatment of mania. The Depakote Mania Study Group.", "Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder.", "Valproate as an adjunct to neuroleptic medication for the treatment of acute episodes of mania: a prospective, randomized, double-blind, placebo-controlled, multicenter study. European Valproate Mania Study Group.", "A double-blind comparison of valproate and lithium in the treatment of acute mania.", "A randomized comparison of divalproex oral loading versus haloperidol in the initial treatment of acute psychotic mania." ]

[ "Achieving therapeutic blood levels of a mood stabilizer as quickly as possible is desirable in patients with acute mania. We examined the feasibility and safety of an accelerated oral loading strategy (divalproex, 30 mg/kg/day, on days 1 and 2, followed by 20 mg/kg/day on days 3-10) designed to bring serum valproate concentrations to therapeutic levels (i.e., above 50 microg/mL).\n Fifty-nine patients who met DSM-IV diagnostic criteria for current manic episode and who had a Mania Rating Scale score > or = 14 were randomly assigned on a double-blind basis to receive divalproex oral loading (N = 20); divalproex nonloading (N = 20) at a starting dose of 250 mg t.i.d. on days 1 and 2, followed by standard dose titration for days 3 to 10; or lithium carbonate (N = 19) at a starting dose of 300 mg t.i.d., followed by standard dose titration for days 3 to 10.\n Eighty-four percent of the divalproex-loading patients, but only 30% of the divalproex-nonloading patients, had valproate serum levels above 50 microg/mL at day 3 of the study. None of the lithium-treated patients had serum lithium levels above 0.8 mEq/L at study day 3. No patient was removed from the study because of an adverse event. There were no significant differences between the groups in the frequencies or types of adverse events.\n Accelerated oral loading with divalproex sodium is a feasible and safe method to bring serum valproate concentrations to effective levels rapidly.", "This study compared the efficacy, safety, and tolerability of divalproex and olanzapine in the treatment of acute mania associated with bipolar disorder.\n This randomized, 12-week, double-blind, parallel-group, multicenter study included DSM-IV-defined bipolar disorder type I patients hospitalized for acute mania and randomly assigned to treatment with divalproex or olanzapine. After an inpatient period of up to 21 days, subjects were followed as outpatients. Dose adjustment was permitted during the inpatient period. Efficacy was assessed using change from baseline in Mania Rating Scale (MRS) score to day 21; other efficacy measures included the Brief Psychiatric Rating Scale, the Hamilton Rating Scale for Depression, and the Clinical Global Impressions-Part I, Severity of Illness scale. The primary safety endpoint was change from baseline in weight. Other safety and tolerability endpoints included spontaneous adverse event reporting and changes from baseline in laboratory measures and vital signs.\n 120 subjects (N = 63 divalproex, N = 57 olanzapine) were randomly assigned to treatment. No significant differences between groups were found for any efficacy variable for change from baseline to day 21. Mean MRS score changes from baseline to day 21 were -14.8 for divalproex and -17.2 for olanzapine (p =.210). A significantly (p <.05) greater proportion of olanzapine-treated subjects experienced somnolence, weight gain, edema, rhinitis, and speech disorder (slurred speech); no adverse events were significantly greater in the divalproex group. A number of laboratory measures also demonstrated significant treatment differences, but the clinical significance of many of these is uncertain. Mean body weight changes were significantly greater in the olanzapine group (+ 8.8 lb [+ 4.0 kg]) than the divalproex group (+ 5.5 lb [+ 2.5 kg], p <.050). One death occurred during the study (olanzapine group, diabetic ketoacidosis).\n No significant difference in efficacy was found between treatment groups. Divalproex was associated with a more favorable adverse event profile and significantly less weight gain than olanzapine.", "We conducted a placebo-controlled, double-blind study of valproate, a drug originally developed as an antiepileptic, in 36 patients with acute manic episodes who had previously failed to respond to or to tolerate lithium carbonate. Treatment duration was 7 to 21 days, with no other psychotropic medications permitted except lorazepam up to 4 mg/d during the first 10 days of treatment. Serum valproate concentrations were measured three times weekly; an unblinded investigator then adjusted dosage to produce serum concentrations between 50 and 100 mg/L. Valproate proved superior to placebo in alleviating manic symptoms. The 17 patients randomized to active drug demonstrated a median 54% decrease in scores on the Young Mania Rating Scale as compared with a median 5.0% decrease among the 19 patients receiving placebo. On the 100-point Global Assessment Scale of overall psychiatric functioning, patients receiving valproate improved by a median of 20 points as compared with a zero-point change with placebo. Significant differences also emerged on the Brief Psychiatric Rating Scale and in the number of supplemental doses of lorazepam required by the patients in each group. Substantial antimanic effects appeared within 1 to 4 days of achieving therapeutic serum valproate concentrations. Adverse effects were infrequent, with no adverse effect appearing significantly more frequently with valproate than with placebo. We conclude that valproate represents a useful new drug for the treatment of manic patients.", "Search for alternatives to lithium therapy for mood disorders commenced with anticonvulsants, carbamazepine (CBZ) and valproic acid (VPA), in the late 1970s. The comparative safety and efficacy data of CBZ and VPA monotherapy in patients with bipolar disorder remain to be established.\n The main objectives of the study were to assess the relative antimanic efficacy and safety of CBZ and VPA; to study the feasibility of using either, as a first line anti-manic agent; to investigate and generate clinically relevant parameters involving therapeutic drug monitoring of the two drugs.\n After a 2-day screening period, suitable patients (n = 30) were randomly assigned to treatment with CBZ or VPA. Both the drugs were started with an average dose of approximately 20 mg/kg body weight per day. Further increment in dose was carried out at weekly intervals, guided by clinical improvement, serum levels and treatment emergent adverse events. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. A favourable clinical response was defined a priori as a decrease of more than 50% from baseline in Young Mania Rating Scale total score.\n Both CBZ and VPA were found to be efficacious as single first-line anti-manic agents, however VPA proved to be better. Using the intent-to-treat analysis, the VPA group showed a significant fall in YMRS total scores after week 1 while the CBZ group showed a significant fall after week 2. In the primary efficacy analysis, valproate group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the CBZ group. Of the VPA treated patients, 73% showed a favourable clinical response while 53% of the patients on CBZ responded favourably. In the CBZ group, significantly more patients received rescue medication during the week 2 and the requirement was quantitatively more as compared to the VPA group. The steady state serum concentration (Css) of CBZ ranged from 3 to 9 micrograms/ml; however, it did not appear to correlate with the dose or clinical response. The Css of VPA ranged from 50 to 100 micrograms/ml; a linear correlation was found between the dose and serum levels of VPA as well as between weekly rise in serum levels and clinical response. Weekly dose escalations of VPA also correlated positively with corresponding rise in serum levels. Significantly more patients in the CBZ group reported adverse events, including nausea, vomiting and dizziness, than VPA.\n The findings from this study suggest that both CBZ and VPA monotherapy is feasible for treatment of acute mania; however, VPA is more efficacious in terms of its early onset of action, lesser requirement for rescue medication and better tolerability. Further work needs to be undertaken to characterise the manic patients in terms of their differential psychopharmacologic response profile.", "To compare the effectiveness of divalproex sodium with that of lithium and placebo in patients with acute mania.\n Randomized, double-blind, parallel-group study of treatment outcomes in patients with manic-depressive illness.\n A total of 179 hospitalized, acutely manic patients meeting the Research Diagnostic Criteria for manic disorder, approximately half of whom had been nonresponsive to lithium previously, were studied at nine university-affiliated hospitals.\n After a minimum 3-day washout period, random assignment for 21 days to divalproex, lithium, or placebo in a 2:1:2 ratio. Dosage of divalproex and lithium was increased if tolerated to a target concentration of 1041 mumol/L (150 micrograms/mL) or 1.5 mmol/L (conventionally expressed as milliequivalents per liter), respectively.\n Primary outcome measures were changes in the Mania Rating scale derived from the Schedule for Affective Disorders and Schizophrenia.\n Intent-to-treat analysis for efficacy was based on data from 68, 35, and 73 patients in the divalproex, lithium, and placebo groups, respectively. Groups were initially comparable except that all eight patients with four or more manic episodes in the previous year were in the divalproex group. In 30%, 33%, and 51% of the above groups, treatment was prematurely terminated due to lack of efficacy, with fewer premature terminations from divalproex than placebo (P = .017). The proportions of patients improving at least 50% were higher for divalproex and lithium groups than for the placebo group: 48% for divalproex (P = .004) and 49% for lithium (P = .025) vs 25% for placebo. Divalproex was as effective in rapid-cycling manic patients as in other patients.\n Both divalproex and lithium were significantly more effective than placebo in reducing the symptoms of acute mania. The efficacy of divalproex appears to be independent of prior responsiveness to lithium.", "To develop effect sizes for 3 mood stabilizers--lithium, divalproex sodium, and carbamazepine--for the acute-phase treatment of bipolar I or II disorder, mixed or manic episode, in children and adolescents aged 8 to 18 years.\n Forty-two outpatients with a mean age of 11.4 years (20 with bipolar I disorder and 22 with bipolar II disorder) were randomly assigned to 6 weeks of open treatment with either lithium, divalproex sodium, or carbamazepine. The primary efficacy measures were the weekly Clinical Global Impression Improvement scores and the Young Mania Rating Scale (Y-MRS).\n Using a > or = 50% change from baseline to exit in the Y-MRS scores to define response, the effect size was 1.63 for divalproex sodium, 1.06 for lithium, and 1.00 for carbamazepine. Using this same response measure with the intent-to-treat sample, the response rates were as follows: sodium divalproex, 53%; lithium, 38%; and carbamazepine, 38% (chi 2(2) = 0.85, p = .60). All 3 mood stabilizers were well tolerated, and no serious adverse effects were seen.\n Divalproex sodium, lithium, and carbamazepine all showed a large effect size in the open treatment of children and adolescents with bipolar I or II disorder in a mixed or manic episode.", "To compare the efficacy of sodium valproate administered as adjunct to neuroleptic medication for patients with acute mania with the efficacy of neuroleptics alone, the authors conducted a 21-day, randomized, double-blind, parallel-group, placebo-controlled trial. The study design closely reflected a clinical psychiatric setting in Europe where patients with acute mania commonly receive neuroleptic medication. In this trial, 136 hospitalized patients met the ICD-10 criteria for acute manic episodes; these patients received a fixed dose of 20 mg/kg of body weight of sodium valproate (Orfiril, Desitin Arzneimittel GmbH, Hamburg, Germany) orally, in addition to basic neuroleptic medication, preferably haloperidol and/or perazine. The primary outcome measure was the mean dose of neuroleptic medication (after conversion into haloperidol-equivalents) for the 21-day study period. Severity of symptoms was measured using the Young Mania Rating Scale (YMRS), the Global Assessment Scale, and the Clinical Global Impression Scale. Intent-to-treat analysis was based on 69 patients treated with valproate and 67 patients who received placebo. Groups were comparable with regard to demographic and clinical baseline data. Premature discontinuations occurred in only 13% of the patients. The mean neuroleptic dose declined continuously in the valproate group, whereas only slight variations were observed in the placebo group; the difference was statistically significant (p = 0.0007) for study weeks 2 and 3. The combination of neuroleptic and valproate proved superior to neuroleptics in attempts to alleviate manic symptoms. The proportion of responders (a 50% improvement rate shown on the YMRS) was higher for the combination with valproate than for the group receiving only neuroleptics (70% vs. 46%; p = 0.005). Adverse events consisted of those known for valproate or neuroleptics; the only adverse event was asthenia, which occurred more frequently with the combination therapy. Valproate represents a useful adjunct medication for the treatment of acute manic symptoms. Valproate is beneficial because it allows the administration of fewer neuroleptic medications and produces improved and quicker remission of manic symptoms.", "This study was carried out to compare the efficacy of lithium carbonate with that of valproate in acute mania and to determine whether pretreatment clinical characteristics, such as the presence of a mixed affective state, might predict a differential response to the two drugs.\n Twenty-seven patients meeting DSM-III-R criteria for acute manic episodes underwent a 3-week, randomized, double-blind, parallel-groups trial of treatment with lithium carbonate or valproate. Symptom severity was measured by using the Schedule for Affective Disorders and Schizophrenia, change version (SADS-C), the Global Assessment Scale (GAS), and the Brief Psychiatric Rating Scale (BPRS). Drug effects were compared by using repeated measures analysis of variance (ANOVA).\n At the end of the study, nine of 14 patients treated with valproate and 12 of 13 patients treated with lithium had responded favorably, as measured by changes in the SADS-C mania, BPRS, and GAS scores. Elevated pretreatment SADS-C depression scores were associated with good response to valproate. ANOVA revealed a significant interaction between drug and mixed affective state with respect to treatment response.\n Lithium and valproate were both effective in improving manic symptoms, and lithium was slightly more efficacious overall. Unlike the case with lithium, favorable response to valproate was associated with high pretreatment depression scores. Therefore, treatment with valproate alone may be particularly effective in manic patients with mixed affective states.", "Uncontrolled evidence suggests that divalproex administered via the oral loading strategy of 20 mg/kg/day may produce clinically significant antimanic response within 3 days of treatment in some patients. We conducted a prospective study to compare the antimanic response of divalproex oral loading with that of haloperidol in the initial treatment of acute psychotic mania.\n After a < or = 1-day screening period, 36 consecutive hospitalized patients with bipolar disorder, manic or mixed phase and with psychotic features, were randomly assigned to receive either divalproex 20 mg/kg/day or haloperidol 0.2 mg/kg/day for 6 full days, without other psychotropic agents except lorazepam up to 4 mg/day for management of agitation. Serum valproate concentrations were measured after 1 day of treatment. Response was measured daily by a blind rater using the Young Mania Rating Scale and the Scale for Assessment of Positive Symptoms.\n Divalproex oral loading and haloperidol were equally effective in acutely reducing manic and psychotic symptoms. The greatest rate of improvement for both drug regimens occurred over the first 3 full days of treatment. Side effects were infrequent and minor for both treatments, except for extrapyramidal side effects which were significantly more common with haloperidol.\n Divalproex oral loading may produce rapid onset of antimanic and antipsychotic response comparable to that of haloperidol and with minimal side effects in the initial treatment of acute psychotic mania in a subset of bipolar patients." ]

[ "21180275", "18246387", "12357142", "9602583", "11888456", "17457160", "16793612", "18791356", "16521223" ]

[ "Effects of acute normovolemic hemodilution on perioperative coagulation and fibrinolysis in elderly patients undergoing hepatic carcinectomy.", "Effect of infra-hepatic inferior vena cava clamping on bleeding during hepatic dissection: a prospective, randomized, controlled study.", "Effectiveness of acute normovolemic hemodilution to minimize allogeneic blood transfusion in major liver resections.", "Bovine haemoglobin-based oxygen carrier for patients undergoing haemodilution before liver resection.", "Effect of hypoventilation on bleeding during hepatic resection: a randomized controlled trial.", "Intraoperative blood salvage during liver resection: a randomized controlled trial.", "[Acute normovolemic hemodilution combined with controlled hypotension in patients undergoing liver tumorectomy].", "A prospective randomized trial of acute normovolemic hemodilution compared to standard intraoperative management in patients undergoing major hepatic resection.", "Low central venous pressure reduces blood loss in hepatectomy." ]

[ "To observe the effects of acute normovolemic hemodilution (ANH) on coagulation function and fibrinolysis in elderly patients undergoing hepatic carcinectomy.\n Thirty elderly patients (aged 60-70 years) with liver cancer (American Society of Anesthesiologists physical status I-II) scheduled for hepatic carcinectomy from February 2007 to February 2008 were randomly divided into ANH group (n = 15) and control group (n = 15). After tracheal intubation, patients in ANH group and control group were infused with 6% hydroxyethyl starch (HES) (130/0.4), and basic liquid containing 6% HES and routine Ringer's solution, respectively. In all the studied patients, blood samples were drawn at five different time points: before anesthesia induction (T1), 30 minutes after ANH (T2), 1 hour after start of operation (T3), immediately after operation (T4), and 24 hours after operation (T5). Then coagulation function, soluble fibrin monomer complex (SFMC), prothrombin fragment (F1+2), and platelet membrane glycoprotein (activated GPIIb/GPIIIa and P-selectin) were measured.\n The perioperative blood loss was not significantly different between the two groups (P > 0.05). The volume of allogeneic blood transfusion in ANH group was significantly smaller than that in control group (350.5 +/- 70.7 mL vs. 457.8 +/- 181.3 mL, P < 0.01). Compared with the data of T1, prothrombin time (PT) and activated partial thromboplastin time in both groups prolonged significantly after T3 (P < 0.05), but still within normal range. There were no significant changes in thrombin time and D-dimer between the two groups and between different time points in each group (all P > 0.05). SFMC and F1 + 2 increased in both groups, but without statistical significance. P-selectin expression on the platelet surface of ANH group was significantly lowered at T2 and T3 compared with the level at T1 (P < 0.05). Compared with control group, P-selectin was significantly lower in ANH group at T2-T5 (all P < 0.05).\n In elderly patients undergoing resection of liver cancer, ANH may not hamper fibrinolysis and coagulation function. It could therefore be safe to largely reduce allogeneic blood transfusion.", "The success of hepatectomy can be associated with intraoperative blood loss because massive blood loss causes a poor prognosis. This study was designed to evaluate the effect of infrahepatic inferior vena cava (IVC) clamping on the bleeding amount during hepatectomy.\n Eighty-five patients scheduled to undergo hepatic resection were randomly assigned to the IVC clamping or an IVC nonclamping group according to age, indocyanine green retention rate at 15 minutes, operative procedure, and number of tumors by prospective, randomized method. All analyses were compared by Mann-Whitney U test.\n Forty-three patients were assigned to the IVC clamping group and 42 to the nonclamping group (IVC clamping group vs. non-clamping): total blood loss (499 vs. 584 ml; p = 0.567), amount of bleeding during hepatectomy (233 vs. 285 ml; p = 0.474), amount of bleeding during hepatectomy/area of dissection (4.9 vs. 6.6 ml/cm(2); p = 0.63), CVP difference (-3 cmH(2)O vs. -1 cmH(2)O; p < 0.01), and diameter of the right hepatic vein (-2.2 cm vs. 0; p < 0.01).\n Although we had speculated that infrahepatic IVC clamping would reduce blood loss during hepatectomy, we failed to demonstrate any beneficial effects in this clinical setting with low CVP.", "Liver resection is a major operation for which, even with the improvements in surgical and anesthetic techniques, the reported rate of blood transfusion was rarely less than 30%. About 60% of transfused patients require only 1 or 2 units of blood, a blood requirement that may be accommodated by the use of acute normovolemic hemodilution (ANH).\n The efficacy, hemodynamic effects, and safety of ANH were investigated in a randomized, active-control study in patients with American Society of Anesthesiologists status I-II who were undergoing major liver resection with fentanyl-nitrous oxide-isoflurane anesthesia. Patients were randomized to the ANH (n = 39) or control group (n = 39). Patients in the ANH group underwent hemodilution to a target hematocrit of 24%. The indication for blood transfusion was standardized. In both groups transfusion was started at a hematocrit of 20%. The primary efficacy endpoint was the avoidance of allogeneic blood transfusion in the intraoperative period and first 72 h after surgery. Various laboratory and hemodynamic parameters as well as postoperative morbidity were monitored to define the safety of ANH in this patient population.\n During the perioperative period, 14 control patients (36%) received at least one unit of allogeneic blood compared with 4 patients (10%) in the ANH group ( < 0.05). The hemodilution process was not associated with significant changes in patients' hemodynamics. Morbidity was similar between the control and the ANH groups. Postoperative hematocrit levels and biochemical liver, renal, and standard coagulation test results were similar in both groups.\n Acute normovolemic hemodilution in patients with American Society of Anesthesiologists status I-II undergoing major liver resection may allow a significant number of patients to avoid exposure to allogeneic blood.", "We have studied the use of ultrapurified polymerized bovine haemoglobin (HBOC-201) in patients undergoing preoperative haemodilution before liver resection. After autologous blood donation of 1 litre, 12 patients (six males, six females, mean age 59 (35-69) yr) received Ringer's lactate solution 2 litre and, in a random design, 6% hydroxyethyl starch 70,000/0.5 (HES) 3 ml kg-1 or HBOC-201 0.4 g kg-1 within 30 min. Blood samples were obtained for blood chemistry, co-oximetry, haematology, coagulation profiles and immunology examinations before operation, on the day of surgery, on days 2-4 and 7 after operation, on the discharge day and 3 months after operation. There were no differences in patient characteristics, blood loss, amount of solutions infused, transfused allogeneic blood or duration of hospital stay. There were no local or systemic allergic reactions with infusion of HES or HBOC-201. Patients receiving HBOC-201 developed more pronounced leucocytosis and reticulocytosis during the early postoperative days compared with HES-treated patients. The mean maximum plasma haemoglobin concentration was 1.0 (SD 0.2) g dl-1 at the end of infusion of HBOC-201 was 8.5 h. Patients in both groups experienced temporary changes in liver enzymes and coagulation variables which returned to normal before discharge. Urinalysis revealed no difference between groups and no free haemoglobin was detected in urine. Patients receiving HBOC-201 showed no IgE and only a slight increase in IgG titres to HBOC-201 on the day of discharge; these were not detectable at 3 months. Single-dose administration of HBOC-201 was well tolerated by patients undergoing elective liver resection surgery and appears to be safe as a substitute during preoperative haemodilution.", "Blood loss in hepatic resection is an important determinant of operative outcome.\n To clarify whether reducing the tidal volume would be effective in decreasing blood loss during liver transection.\n Randomized controlled trial.\n University hospital.\n Eighty patients scheduled to undergo hepatic resection were randomly assigned to receive liver transection under normoventilation (n = 40) or hypoventilation (n = 40).\n During liver transection, in the normoventilation group, the tidal volume was 10 mL/kg and the respiratory rate was 10/min; in the hypoventilation group, the tidal volume was reduced to 4 mL/kg and respiratory rate was increased to 15/min. Liver transection was performed under total or selective inflow occlusion.\n Blood loss.\n Between the normoventilation and hypoventilation groups, no significant difference was found in total blood loss (median [range]: 630 mL [72-3600 mL] vs 630 mL [120-3520 mL]; P =.44) or blood loss per transection area (median [range]: 7.3 mL/cm(2) [1.2-55.4 mL/cm(2)] vs 9.8 mL/cm(2) [0.9-79.9 mL/cm(2)]; P =.55). During liver transection, the central venous pressure was significantly reduced in the hypoventilation group than in the normoventilation group (median [range]: -0.7 cm H(2)O [-3.0 to 1.8 cm H(2)O] vs -0.2 cm H(2)O [-4.0 to 2.0 cm H(2)O]; P =.007). The maximum end-tidal carbon dioxide level in the hypoventilation group was significantly higher than that in the normoventilation group (maximum [range]: 50 mm Hg [28-66 mm Hg] vs 37 mm Hg [27-60 mm Hg]; P<.001). Transection time, postoperative liver function, hospitalization length, morbidity, and mortality were similar in the 2 groups.\n This randomized trial suggested no beneficial effect of reduction of tidal volume on bleeding during hepatic resection.", "A randomized controlled trial was conducted to clarify the effectiveness of intraoperative blood salvage in reducing blood loss.\n Although reduction of central venous pressure (CVP) is thought to decrease blood loss during liver resection, no consistently effective and safe method for obtaining the desired reduction of CVP has been established.\n Living liver donors scheduled to undergo liver graft procurement were randomly assigned to a blood salvage group, in which a blood volume equal to approximately 0.7% of the patient's body weight was collected before the liver transection, or a control group. The surgeons were blinded to the randomization results. The primary outcome measure was blood loss during liver parenchymal division. A multivariate analysis was also performed.\n Seventy-nine donors were allocated intraoperatively to the blood salvage group (n = 40) or the control group (n = 39). The amount of blood loss during liver transection was significantly smaller in the blood salvage group than in the control group (median loss during transection, 140 mL vs. 230 mL, P = 0.034). The CVP at the beginning of the liver parenchymal division was significantly lower in the blood salvage group than in the control group (median, 5 cm H2O vs. 6 cm H2O, P = 0.005). The results of a multivariate analysis revealed that intraoperative blood salvage offered the advantage of reduced blood loss during liver parenchymal division (adjusted OR, 0.31; 95% CI, 0.11-0.85, P = 0.025).\n Modest intraoperative blood salvage significantly and safely reduced blood loss during hepatic parenchymal transection.", "To evaluate the effects of acute normovolemic hemodilution (ANH) combined with controlled hypotension on reducing heterogeneous transfusion and safety during liver tumorectomy.\n Thirty patients undergoing elective liver tumorectomy were randomly divided into 3 groups (10 each), namely ANH group (group A), ANH combined with controlled hypotension group (group B) and control group (group C). All the patients were anesthetized via endotracheal intubation. Before the operation, ANH was performed in groups A and B after anesthesia induction, and controlled hypotension was initiated in group B during tumorectomy. Blood transfusion and fluid infusion were carried out routinely in group C. Hb and Hct were measured before operation, after ANH, and immediately, 1 day and 7 days after the operation. The difference in intraoperative blood loss and heterogeneous blood transfusion volume in the 3 groups was observed.\n In group A, heterogeneous blood transfusion was avoided in 6 cases and but given in the other cases for an average of 400 ml. In group C, every patient received heterogeneous blood transfusion (664.8-/+248.1 ml), but none of the patients received heterogeneous blood in group B. The difference in transfusion volume between the 3 groups was significant (P<0.01). Hemodynamics was basically stable during operation in the 3 groups.\n ANH combined with controlled hypotension is safe and effective for decreasing and even avoiding homologous blood transfusion in liver tumorectomy.", "Hepatic resection is the most effective treatment for many malignant and benign conditions affecting the liver and biliary tree. Despite improvements, major partial hepatectomy can be associated with considerable blood loss and transfusion requirements. Transfusion of allogeneic blood products, although potentially life-saving, is associated with many potential complications. The primary aim of this study was to determine if acute normovolemic hemodilution (ANH), an established blood conservation technique, reduces the requirement for allogeneic red cell transfusions in patients undergoing major hepatic resection.\n One hundred thirty patients undergoing major hepatic resection (> or =3 segments) were prospectively randomized to undergo either ANH or standard anesthetic management (STD). In the ANH group, intraoperative blood collection was performed to a target hemoglobin of 8.0 g/dL. Low central venous pressure anesthetic technique was used intraoperatively for both groups. A standardized transfusion protocol was applied to all patients intraoperatively and throughout the hospital stay.\n From April 2004 to March 2007, 63 patients were randomized to ANH and 67 to STD. Demographics, diagnoses, liver function, extent of resection, intraoperative blood loss, operative time, incidence and grade of complications, and length of hospital stay were similar between the 2 groups. ANH reduced the overall allogeneic red cell transfusion rate by 50% compared with STD [12.7% (n = 8) vs. 25.4% (n = 17), respectively; P = 0.067. ANH patients were less often transfused intraoperatively (n = 1, 1.6%) compared with the STD group (n = 7, 10.4%) (P = 0.036), had higher postoperative hemoglobin levels (P = 0.01), and tended to require fewer red cell units overall (28 vs. 47 units). In patients with intraoperative blood loss > or =800 mL, ANH reduced not only the allogeneic red cell transfusion rate (18.2% vs. 42.4%, P = 0.045) but also the proportion of patients requiring fresh frozen plasma (21.1% vs. 48.3%, P = 0.025).\n For patients undergoing major liver resection, ANH is safe, effectively reduces the need for allogeneic transfusions, and should be considered for routine use. Given the modest transfusion rate in the STD arm, future efforts should attempt to target ANH use to patients most likely to benefit.", "To investigate the effect of low central venous pressure (LCVP) on blood loss during hepatectomy for hepatocellular carcinoma (HCC).\n By the method of sealed envelope, 50 HCC patients were randomized into LCVP group (n=25) and control group (n=25). In LCVP group, CVP was maintained at 2-4 mmHg and systolic blood pressure (SBP) above 90 mmHg by manipulation of the patient's posture and administration of drugs during hepatectomy, while in control group hepatectomy was performed routinely without lowering CVP. The patients' preoperative conditions, volume of blood loss during hepatectomy, volume of blood transfusion, length of hospital stay, changes in hepatic and renal functions were compared between the two groups.\n There were no significant differences in patients' preoperative conditions, maximal tumor dimension, pattern of hepatectomy, duration of vascular occlusion, operation time, weight of resected liver tissues, incidence of post-operative complications, hepatic and renal functions between the two groups. LCVP group had a markedly lower volume of total intraoperative blood loss and blood loss during hepatectomy than the control group, being 903.9+/-180.8 mL vs 2 329.4+/-2 538.4 (W=495.5, P<0.01) and 672.4+/-429.9 mL vs 1 662.6+/-1 932.1 (W=543.5, P<0.01). There were no remarkable differences in the pre-resection and post-resection blood losses between the two groups. The length of hospital stay was significantly shortened in LCVP group as compared with the control group, being 16.3+/-6.8 d vs 21.5+/-8.6 d (W=532.5, P<0.05).\n LCVP is easily achievable in technique. Maintenance of CVP<or= 4 mmHg can help reduce blood loss during hepatectomy, shorten the length of hospital stay, and has no detrimental effects on hepatic or renal function." ]

[ "15486837", "12971556", "15189457", "15839740", "15548313", "15850631", "11132386", "15850630", "11463111" ]

[ "Randomized comparison of chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in the Lao People's Democratic Republic.", "Comparative clinical trial of two-fixed combinations dihydroartemisinin-napthoquine-trimethoprim (DNP) and artemether-lumefantrine (Coartem/Riamet) in the treatment of acute uncomplicated falciparum malaria in Thailand.", "[Efficacy of therapeutic combinations with artemisinin derivatives in the treatment of non complicated malaria in Burundi].", "Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-artemether.", "Therapeutic efficacy of artemether-lumefantrine and artesunate-mefloquine for treatment of uncomplicated Plasmodium falciparum malaria in Luang Namtha Province, Lao People's Democratic Republic.", "Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial.", "Artemether-lumefantrine for the treatment of multidrug-resistant falciparum malaria.", "Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial.", "A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand." ]

[ "Recent clinical trials in the Lao People's Democratic Republic have demonstrated that chloroquine and sulfadoxine-pyrimethamine, which are national malaria treatment policy, are no longer effective in the treatment of uncomplicated Plasmodium falciparum malaria.\n A randomized comparison of 3 oral antimalarial combinations--chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine--with 42-day follow-up period, was conducted among 330 patients with acute uncomplicated falciparum malaria in southern Laos.\n The 42-day cure rates, as determined by intention-to-treat analysis and adjusted for reinfection, were 100%, 97%, and 93% for the groups receiving artesunate plus mefloquine, artemether-lumefantrine, and chloroquine plus sulfadoxine-pyrimethamine, respectively. Of 8 patients receiving chloroquine plus sulfadoxine-pyrimethamine who experienced treatment failure, 6 had early treatment failure. The mean parasite clearance time was significantly longer in patients treated with chloroquine plus sulfadoxine-pyrimethamine (2.9 days; 95% confidence interval [CI], 2.8-3.0 days) than in those treated with artesunate plus mefloquine (2.07 days; 95% CI, 2.0-2.1 days; P<.001) and artemether-lumefantrine (2.08 days; 95% CI, 2.0-2.1 days; P<.001). Cure rates with artemether-lumefantrine were high despite low mean daily dietary fat intake (13.8 g; 95% CI, 12.5-15.1 g) and day 7 plasma lumefantrine concentrations (0.47 mu g/mL; 95% CI, 0.38-0.56 mu g/mL).\n Oral artesunate plus mefloquine and artemether-lumefantrine are highly effective for the treatment of uncomplicated falciparum malaria in Laos.", "An open randomized comparison of two-fixed dose artemisinin derivative-containing combination regimens was conducted in adults with acute uncomplicated multidrug resistant falciparum malaria in Thailand. DNP, a combination of dihydroartemisinin with napthoquine and trimethoprim developed recently in China, has been evaluated in China, Vietnam, Cambodia and Thailand. This study was performed to compare the safety, tolerability and efficacy of DNP and artemether-lumefantrine/Coartem. One hundred and thirty eligible uncomplicated falciparum malaria patients were enrolled into the study. Patients were randomly assigned in a 2:1 ratio into group A, which received DNP one tablet twice a day for one day; and group B, which received Coartem/Riamet four tablets twice a day for 3 days. The cure rates at 28-day were 99% and 97% in group A and group B, respectively. No serious adverse events occurred. We concluded that both DNP and Coartem/ Riamet were safe, well tolerated and highly efficacious in the treatment of acute uncomplicated falciparum malaria in Thailand.", "Faced with the problem of resistance to chloroquine and sulfadoxine-pyrimethamine, the Ministry of Public Health of Burundi decided to study the efficacy of two artemisinin-based combinations, the fixed combination of artemether-lumefantrine and the combination of amodiaquine + artesunate. The efficacy of these combinations for the treatment of uncomplicated falciparum malaria was studied in two sites representative of the country, in Kigobe neighbourhood of Bujumbura, the capital city, and in Buhiga, a rural area. The study followed the standardized WHO protocol from October 2001 to November 2002. A total of 295 children under 5 years were included; 153 children were treated with artesunate and amodiaquine (77 at Buhiga and 76 at Kigobe), and 142 children with the combination of artemether-lumefantrine (64 at Buhiga and 78 at Kigobe). Among the 295 children, 290 were followed up to 14 days. In the group of 149 children treated with artesunate and amodiaquine, 142 (95.3%, 95% CI: 91.9-98.7%) presented with adequate clinical and parasitological response, five (3.3%) with late parasitological failure, one (0.7%) with late clinical failure and one (0.7%) with early treatment failure. Among the 141 children treated with artemether-lumefantrine, 140 (99.3%, 95% CI: 97.9-100%) presented with adequate clinical and parasitological response and one (0.7%) with late parasitological failure at Buhiga. Side-effects were comparable in both groups except for the vomiting. Vomiting was more frequent in the artesunate + amodiaquine on D1 and D2. Both treatments decreased the gametocyte carriage but without getting full clearance in all the patients. During a consensus workshop, the Ministry of Public Health agreed on the combination of artesunate and amodiaquine as the first line drug for the treatment of uncomplicated falciparum malaria in Burundi including epidemic outbreak.", "Resistance of malaria parasites to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) is increasing in prevalence in Africa. Combination therapy can both improve treatment and provide important public health benefits if it curbs the spread of parasites harbouring resistance genes. Thus, drug combinations must be identified which minimise gametocyte emergence in treated cases, and so prevent selective transmission of parasites resistant to any of the partner drugs.\n In a randomised controlled trial, 497 children with uncomplicated falciparum malaria were treated with CQ and SP (three doses and one dose respectively; n = 91), or six doses of artemether in fixed combination with lumefantrine (co-artemether [Coartem, Riamet]) (n = 406). Carriage rates of Plasmodium falciparum gametocytes and trophozoites were measured 7, 14, and 28 d after treatment. The infectiousness of venous blood from 29 children carrying P. falciparum gametocytes 7 d after treatment was tested by membrane-feeding of Anopheles mosquitoes. Children treated with co-artemether were significantly less likely to carry gametocytes within the 4 weeks following treatment than those receiving CQ/SP (30 of 378 [7.94%] versus 42 of 86 [48.8%]; p < 0.0001). Carriers in the co-artemether group harboured gametocytes at significantly lower densities, for shorter periods (0.3 d versus 4.2 d; p < 0.0001) and were less infectious to mosquitoes at day 7 (p < 0.001) than carriers who had received CQ/SP.\n Co-artemether is highly effective at preventing post-treatment transmission of P. falciparum. Our results suggest that co-artemether has specific activity against immature sequestered gametocytes, and has the capacity to minimise transmission of drug-resistant parasites.", "The efficacy of the six-dose regimen of artemether-lumefantrine was compared with the combination of artesunate and mefloquine in a randomised, comparative trial in Luang Namtha Province, Northern Laos. Of 1033 screened patients, 201 were positive for Plasmodium falciparum; 108 patients of all age groups (2-66 years) with acute, uncomplicated P. falciparum malaria were enrolled in the study, 100 of whom were followed-up for 42 days. Fifty-three patients received artemether-lumefantrine and 55 received artesunante-mefloquine. Both drug combinations induced rapid clearance of parasites and malaria symptoms; there was no significant difference in the initial therapeutic response parameters. Both regimes were well tolerated. After 42 days, cure rates were 93.6% (95% CI = 82.5-98.7%; 44 of 47 patients) for artemether-lumefantrine and 100% (95% CI = 93.3-100.0%; 53 of 53 patients) for artesunate-mefloquine. The results show the excellent efficacy and tolerability of both artemether-lumefantrine and artesunate-mefloquine in Northern Laos.", "Many countries in Africa are considering a change to combination treatment for falciparum malaria because of the increase in drug resistance. However, there are few effectiveness data for these combinations. Our aim was to study the effectiveness of three drug combinations that have proven efficacious in east Africa compared with amodiaquine monotherapy.\n We undertook a randomised trial of antimalarial drug combinations for children (aged 4-59 months) with uncomplicated malaria in Muheza, Tanzania, an area with a high prevalence of resistance to sulfadoxine-pyrimethamine and chloroquine. Children were randomly allocated 3 days of amodiaquine (n=270), amodiaquine +sulfadoxine-pyrimethamine (n=507), or amodiaquine+artesunate (n=515), or a 3-day six-dose regimen of artemether-lumefantrine (n=519). Drugs were taken orally, at home, unobserved by medical staff. The primary endpoint was parasitological failure by day 14 assessed blind to treatment allocation. Secondary endpoints included day 28 follow-up and gametocyte carriage. Analysis was by intention to treat.\n Of 3158 children screened, 1811 were randomly assigned treatment and 1717 (95%) reached the 14-day follow-up. The amodiaquine group was stopped early by the data and safety monitoring board. By day 14, the parasitological failure rates were 103 of 248 (42%) for amodiaquine, 97 of 476 (20%) for amodiaquine+sulfadoxine-pyrimethamine, 54 of 491 (11%) for amodiaquine+artesunate, and seven of 502 (1%) for artemether-lumefantrine. By day 28, the parasitological failure rates were 182 of 239 (76%), 282 of 476 (61%), 193 of 472 (40%), and 103 of 485 (21%), respectively. The difference between individual treatment groups and the next best treatment combination was significant (p<0.001) in every case. Recrudescence rates by day 28, after correction by genotyping, were 48.4%, 34.5%, 11.2%, and 2.8%, respectively.\n The study shows how few the options are for treating malaria where there is already a high level of resistance to sulfadoxine-pyrimethamine and amodiaquine. The WHO-packaged six-dose regimen of artemether-lumefantrine is effective taken unsupervised, although cost is a major limitation.", "The efficacy and safety of the 6-dose regimen of artemether-lumefantrine were assessed in an open randomized trial in children and adults presenting with acute, uncomplicated Plasmodium falciparum malaria in Thailand between November 1997 and March 1998. 200 patients were enrolled in 2 centres: 150 received artemether-lumefantrine (i.e., a median total dose of 9.6 mg/kg [interquartile range 8.7-10.7] and 57.9 mg/kg of lumefantrine [52.4-64.0]) and 50 the standard combination of artesunate (12 mg/kg over 3 d) and mefloquine (25 mg/kg). All patients had rapid initial clinical and parasitological responses. The 28 d cure rates were high: 97.7% (95% confidence interval [95% CI] 93.5-99.5%) for artemether-lumefantrine and 100% (95% CI 92.5-100%) for artesunate-mefloquine. The 6-dose regimen of artemether-lumefantrine was better tolerated than, and as effective as, artesunate-mefloquine, the current standard treatment in this area of multidrug-resistant P. falciparum malaria.", "The six-dose regimen of artemether-lumefantrine is effective and is among combination therapies prioritised to replace antimalarials that no longer work in Africa. However, its effectiveness has not been assessed in the field, and could be compromised by poor adherence, incorrect timing of doses, and insufficient intake of fatty foods with every dose. Our aim, therefore, was to assess the effectiveness of artemether-lumefantrine prescribed under routine outpatient conditions, compared with its efficacy when given under supervision to inpatients with acute uncomplicated falciparum malaria.\n We did a randomised trial to compare the efficacy, safety, and pharmacokinetics of artemether-lumefantrine when given in a supervised (all doses observed with fatty-food intake; n=313) or unsupervised (first dose supervised followed by outpatient treatment with nutritional advice; n=644) setting to patients of all ages (weight >10 kg) with acute, uncomplicated falciparum malaria in Mbarara, Uganda. Our primary endpoint was 28 day, PCR-adjusted, parasitological cure rate. Analysis was by intention to treat and evaluability analysis.\n 38 patients were lost to follow-up and one withdrew consent. Day-28 cure rates were 97.7% (296 of 303) and 98.0% (603 of 615) in the supervised and unsupervised groups, respectively. We recorded 15 non-severe, drug-related adverse events, all of which resolved.\n Artemether-lumefantrine has a high cure rate irrespective of whether given under supervision with food or under conditions of routine clinic practice. If used as first-line treatment, artemether-lumefantrine could make a substantial contribution to malaria control in Africa, though cost is an issue.", "The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether-lumefantrine (Coartem/Riamet; Novartis Pharma AG, Basel, Switzerland) were assessed in a randomized trial in 219 patients (> or = 12 years old) with acute, uncomplicated Plasmodium falciparum malaria in Thailand. One hundred and sixty-four patients received artemether-lumefantrine and 55 received the standard treatment combination of mefloquine-artesunate. Both drugs induced rapid clearance of parasites and malaria symptoms. The 28-day cure rates were 95.5% (90% confidence interval [CI] = 91.7, 97.9%) for artemether-lumefantrine and 100% (90% CI = 94.5, 100%) for mefloquine-artesunate. This high-dose regimen of artemether-lumefantrine was very well tolerated, with very good compliance. The most frequent adverse events were headache, dizziness, nausea, abdominal pain, dyspepsia, vomiting, and skin rash. Overall, only 2% of patients in both groups showed QTc prolongations but without any cardiac complication, and no differences were seen between patients with and without measurable baseline plasma levels of quinine or mefloquine. Plasma levels of artemether, dihydroartemisinin, and lumefantrine were consistent with historical data for the same dose regimen, and were higher, particularly for lumefantrine, than those previously observed with the four-dose regimen, explaining the greater efficacy of the six-dose regimen in a drug-resistant setting. These results confirm the excellent safety and efficacy of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug-resistant P. falciparum malaria." ]

[ "17496674", "10219721", "3896355", "6435067" ]

[ "Neuromonics Tinnitus Treatment: third clinical trial.", "The influence of training on tinnitus perception: an evaluation 12 months after tinnitus management training.", "A clinical study of tinnitus maskers.", "Prospective crossover evaluation of four methods of clinical management of tinnitus." ]

[ "The Neuromonics Tinnitus Treatment combines the use of a novel approach to acoustic stimulation with a structured program of counseling and support by a clinician specifically trained in tinnitus rehabilitation. The distinctive acoustic component has been designed to provide stimulation to auditory pathways deprived by hearing loss, engage positively with the limbic system, and allow intermittent, momentary tinnitus perception within a pleasant and relaxing stimulus, thereby facilitating desensitization to the tinnitus signal. The purposes of this study were (1) to demonstrate the efficacy of the treatment, when enhanced with various modifications since previously reported trials and (2) to test the relative clinical effectiveness of two variations of the approach. In the first, intermittent tinnitus perception was facilitated throughout treatment through the use of a stimulus in which intensity peaks allowed the patients' tinnitus perception to be completely covered up, whereas in the intensity troughs their tinnitus was briefly discernible. In the second, subjects experienced little tinnitus perception while listening to the treatment for the first 2 mo, then experienced intermittent perception.\n Thirty-five subjects with a predominantly moderate to severe level of tinnitus-related distress before treatment were randomly allocated into one of two treatment groups, corresponding to the two stage-based variations of the Neuromonics Tinnitus Treatment. Participants were provided with a high-fidelity personal sound player with earphones and an acoustic stimulus that had been spectrally modified according to their individual audiometric profile. They were instructed to use the acoustic stimulus for at least 2 hr per day, particularly at those times when their tinnitus was usually disturbing. Each group had equal amounts of clinician time for education, monitoring, and support.\n At 2, 4, 6, and 12 mo after commencing treatment, both groups displayed clinically and statistically significant improvements in tinnitus distress, awareness, and minimum masking levels as well as loudness discomfort levels. Improvements increased with time over the first 6 mo of therapy, at which time 91% of all subjects across the two groups reported an improvement in tinnitus disturbance (as measured by the Tinnitus Reaction Questionnaire) of at least 40%, with a mean improvement of 65%. Also, 80% of subjects at 6 mo reported a level of tinnitus disturbance that was no longer clinically significant. There was some indication of a more consistent benefit over 12 mo for the group that was provided initially with a high level of tinnitus interaction; however, inter-group differences were not statistically significant. A relation between reported treatment usage (hours per day) and clinical outcomes was observed, suggesting that a \"dosage effect\" may apply with the stimulus provided.\n This study found that the Neuromonics Tinnitus Treatment provides rapid and profound improvements to the severity of tinnitus symptoms and their effect on the subject's quality of life. This was a consistent effect, provided by a treatment that subjects reported as being pleasant to use. Both of the stage-based variations of the treatment that were tested in this study were shown to be successful in achieving these outcomes.", "Sixty-five subjects were reviewed 12 months after tinnitus management training, which had been comprised variously of information, relaxation training and a therapeutic noise strategy. Seventy-four per cent of subjects reported increased habituation to tinnitus (n = 48), 65% reported reduced tinnitus annoyance (n = 42), and 52% reported an increased ability to cope with tinnitus (n = 34). Twenty-five per cent of subjects reported deterioration in coping ability (n = 16), 23% reported reduced habituation to tinnitus (n = 15) and 8% reported increased tinnitus-related annoyance (n = 5). None of the management strategies were found to be significantly more effective than others in facilitating improved coping or habituation to tinnitus. Subjects who reported reduced coping and habituation to tinnitus experienced greater levels of general life stress than subjects who reported increased habituation and coping ability. The use of relaxation therapies as applied in this study did not appear to influence the level of tinnitus distress or the level of life stress. Thirty-seven per cent of subjects given long-term low-level white noise (LTWN) stimulation reported benefit. However, LTWN stimulation did not significantly alter tinnitus awareness or the minimum masking level (MML) of tinnitus. Long-term low-level white noise stimulation appeared to influence cognitive reaction to tinnitus rather than its physical perception. Subjects who initially had low ability to cope with tinnitus and preferred a more active coping style reported significantly greater benefit from LTWN stimulation than subjects whose primary approach to coping was to regulate the emotional impact of tinnitus.", "This report describes a three-centre study of the effectiveness of tinnitus maskers, combination instruments (masker plus hearing aid), and hearing aids in the management of tinnitus. Some 472 patients entered the study with 382 reaching the first evaluation session after a minimum period of 6 months from fitting, and 206 reaching the second evaluation not less than 6 months after the first. The study included two control groups, by which to assess the comparative benefit to be derived solely from the investigation and counselling of such patients. The principal results were as follows: thorough investigation and careful counselling do much to help the patient; much further benefit is given by tinnitus masking instruments of various kinds; maskers are more often effective than hearing aids, although the latter are frequently the most appropriate first treatment of those patients who have substantial (but not yet treated or insufficiently treated) hearing difficulties as well; there is no evidence of masking having any harmful effect on hearing. None of the audiometric or tinnitus tests currently employed can be regarded as predictive, either of tinnitus severity, or of the eventual outcome of masking therapy, however certain measurements may help as a guide to patient management.", "This article summarizes data obtained from 34 tinnitus-afflicted patients who participated in and completed a prospective crossover evaluation of four methods of clinical management of tinnitus. The methods included a 2-week trial with each of the following: a tinnitus masker, a tinnitus instrument (a combination device consisting of a tinnitus masker and a hearing aid), a hearing aid, and conventional environmental controls. The relative effectiveness of each method of treatment was assessed by interview. The data presented summarize respondents' preferences for each method of treatment. Use of a tinnitus masker, tinnitus instrument, and hearing aid is related to stability of auditory thresholds. Comments are made on our experience with clinical management of the patient afflicted with tinnitus, and observations are offered on continued investigation in this area." ]

[ "10453872", "4166889", "4572567", "3478618", "7656936", "8077885", "2852389", "531541", "16315785" ]

[ "Oral prednisolone followed by inhaled budesonide in newly diagnosed pulmonary sarcoidosis: a double-blind, placebo-controlled multicenter study. Finnish Pulmonary Sarcoidosis Study Group.", "Treatment of sarcoidosis. Report of a controlled therapeutic trial.", "A controlled trial of prednisone treatment of sarcoidosis.", "Corticosteroid therapy in sarcoidosis. A five-year, controlled follow-up study.", "Inhaled budesonide in pulmonary sarcoidosis: a double-blind, placebo-controlled study. Dutch Study Group on Pulmonary Sarcoidosis.", "No effect of high-dose inhaled steroids in pulmonary sarcoidosis: a double-blind, placebo-controlled study.", "Inhaled budesonide influences cellular and biochemical abnormalities in pulmonary sarcoidosis.", "Corticosteroid therapy of pulmonary sarcoidosis. A prospective evaluation of alternate day and daily dosage in stage II disease.", "Effect of beclomethasone dipropionate (BDP) as extrafine aerosol on bronchoalveolar lavage (BAL) lymphocytes in chronic sarcoidosis." ]

[ "To evaluate the efficacy of oral prednisolone, followed by inhaled budesonide, in patients with newly diagnosed (<3 months) stage I and stage II pulmonary sarcoidosis.\n Double-blind, placebo-controlled, parallel-group, multicenter study.\n Twenty pulmonary medicine departments in Finland.\n One hundred eighty-nine adult patients were randomized to treatment. Patients with erythema nodosum or stage IV sarcoidosis (pulmonary fibrosis), and patients requiring immediate treatment with oral corticosteroids for extrapulmonary lesions or chronic illnesses were excluded.\n The patients received either oral prednisolone for 3 months (20 mg/d for 8 weeks, 15 mg/d for 2 weeks, and 10 mg/d for 2 weeks) followed by inhaled budesonide (Pulmicort Turbuhaler; Astra Draco; Lund, Sweden) for 15 months at 800 microg bid, or placebo tablets followed by placebo inhaler therapy.\n Chest radiographs, lung volumes (FVC), diffusing capacity of the lung for carbon monoxide (D(LCO)), serum angiotensin-converting enzyme (SACE), and beta2-microglobulin at 3-month intervals.\n After 3 months of treatment, radiographic improvements were seen in the active-treatment group when compared to the placebo-treatment group. At 6 months, the difference was still statistically significant. Later, no differences were found. In patients with initial stage I lesions, neither the FVC nor the D(LCO) (the percent predicted mean values) changed during the study, as they were normal from the beginning. In patients with initial stage II disease, the difference in the FVC mean values between the groups also remained unchanged throughout the study. In stage II patients treated for 18 months, but not earlier, the difference in D(LCO) became statistically significant; the largest differences were seen in patients with initial FVC values <80% of predicted and D(LCO) values <75% of predicted. The decrease in SACE in the active-treated stage II patients was significantly larger than in the placebo-treated patients. No difference was observed in adverse events between the active-treated patients and the placebo-treated patients.\n Treatment is not required for patients with stage I disease. An initial treatment with prednisolone followed by long-term inhalation of budesonide is more effective than placebo in patients with stage II disease. Sequential oral and inhaled corticosteroid therapy may be an alternative treatment regimen for stage II sarcoidosis patients, rather than long-term oral corticosteroid therapy alone.", "nan", "nan", "nan", "In a double-blind, placebo-controlled study, we assessed the efficacy of inhaled budesonide on the course of newly diagnosed pulmonary sarcoidosis and whether budesonide treatment could postpone oral corticosteroid treatment. We evaluated: 1) symptoms; 2) chest radiography; 3) angiotensin-converting enzyme (ACE) in serum; and 4) lung function. Patients with histologically confirmed pulmonary sarcoidosis with chest radiographic stages I, II or III, and with an abnormal lung function (inspiratory vital capacity (IVC) < 79% of predicted or transfer factor of the lungs for carbon monoxide (TL,CO) < 77% pred) were included. Patients with radiographic stage II or III but with normal lung function were included when more than 20% of the total cell population in bronchoalveolar lavage fluid (BALF) was lymphocytes. Forty seven patients received placebo or budesonide (1.2 mg) once daily via a Nebuhaler for 6 months, followed by 6 months without treatment. Based on predetermined criteria, 11 patients were excluded during the blind treatment period as they needed oral prednisone: seven (28%) patients in the placebo group (n = 25) and four (18%) patients in the budesonide group (n = 22). Patient's Global Clinical Impression (GCI) score showed a significant difference in favour of budesonide. IVC showed a significant difference of 7.9% predicted between the two groups during the active treatment period. This difference persisted during follow-up, when the difference was 9.4% pred. TL,CO remained nearly unchanged over time, with no difference between the groups. Improvements in chest radiographic appearance and changes in serum ACE were similar for the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "To evaluate whether inhaled steroids in high doses might be of therapeutic value in pulmonary sarcoidosis.\n Randomized, double blind and placebo controlled parallel study.\n The out-patient clinic of the Department of Pulmonary Medicine, Gentofte Hospital, Copenhagen, Denmark.\n Twenty-one untreated patients (17 males, 4 females, median age 33 years, range 21-65) and eight patients treated with systemic prednisolone. All patients had biopsy proven pulmonary sarcoidosis radiological stage I-III.\n Treatment with either inhaled budesonide 1.2 mg day-1-2.0 mg day-1 (n = 9) or placebo (n = 12) for 12 months.\n Clinical (cough, chest pain, dyspnoea) and paraclinical variables (chest X-ray, gallium scintigraphy, pulmonary function tests, and biochemical markers of disease activity: blood leukocytes, lymphocytes, serum (S-) angiotensin converting enzyme (ACE), S-1,25-OH-cholecalciferol, plasma (P-) calcium, P-immunoglobulins) were recorded before treatment, every three months during treatment, and 6 months after treatment had been discontinued.\n There were no significant differences between the recorded variables in the budesonide and placebo groups. In general, a regression of disease activity was observed in both groups. Two patients in the treatment group, treated with 2.0 mg budesonide/day, and two in the placebo group had progression in disease and were put on systemic steroids.\n Inhaled budesonide in doses of 1.2-2.0 mg day-1 had no recognizable therapeutic effect on pulmonary sarcoidosis.", "In a randomized, double-blind study 19 patients with newly-detected pulmonary sarcoidosis were treated with either inhaled budesonide, 800 micrograms twice daily (n = 9), or placebo (n = 10) for 8-10 weeks. Before and after treatment, chest roentgenograms, lung function tests, bronchoalveolar lavage (BAL) and biochemical tests were performed. Angiotensin converting enzyme (ACE) activity and beta2-microglobulin (beta 2M) concentrations were measured in serum. The same tests, as well as albumin and hyaluronan were measured in the BAL-fluid. The total cell number in BAL-fluid, differential counts and lymphocyte subpopulations were determined (total T- and B-lymphocytes, T-helper/inducer (OKT-4) and T-suppressor/cytotoxic (OKT-8) lymphocytes). No significant changes in chest roentgenograms or lung function tests were observed during the short study time. However, a decrease in serum ACE (p less than 0.1) and beta 2 M (p less than 0.05) as well as in BAL-hyaluronan (p less than 0.01) was found in the budesonide-treated patients as well as a decrease in the percentage of BAL T-lymphocytes (p less than 0.05) and the T4/T8 ratio (p less than 0.1). No significant changes were seen in the placebo group. The findings suggest that treatment with inhaled budesonide influences biochemical and cellular findings in patients with early sarcoidosis in the same way as treatment with systemic corticosteroids. The results may also explain clinical effects seen in sarcoidosis patients treated with inhaled corticosteroids. However, further studies are required to determine the long-term clinical benefits of inhaled steroids in pulmonary sarcoidosis.", "Thirty-nine sarcoidosis patients with pulmonary infiltrations (stage II) of less than 5 years duration and not treated earlier with corticosteroids were randomly allocated for treatment with methylprednisolone for 7 months or for observation without therapy. Every other treated patient was given the drugs daily and every other followed an alternate-day regimen. After 7 months the chest radiographic finding, the forced vital capacity and the diffusion capacity for carbon monoxide were superior in the treated group. There was no difference between the two drug regimens. After 24 and 48 months no statistically significant differences between the untreated and the treated groups were found.", "Patients with pulmonary sarcoidosis can benefit from inhaled corticosteroids. In this study we assessed the effect of beclomethasone dipropionate (BDP), administered as extrafine, HFA(hydrofluoroalkane)-driven aerosol with high peripheral deposition, on bronchoalveolar lavage (BAL) lymphocyte numbers, as a marker of the disease.\n Fifteen patients with newly-diagnosed pulmonary sarcoidosis (Stages I-III) received either BDP 800 microg daily (n = 6) or placebo (n = 9) for 6 months in a parallel-group design. Before and after treatment, clinical and radiological states were assessed, bronchoalveolar lavage (BAL) performed, and the cellular composition of BAL fluid as well as cytokine production by BAL lymphocytes determined.\n BDP caused a decrease in the percentage of BAL lymphocytes in the BDP (p < 0.05) but not the placebo group. HLA-DR expression on lymphocytes was diminished after BDP (p < 0.05), while intracellular cytokine production by lymphocytes was not altered. Chest radiography suggested an improvement in the BDP group. There was also a rise (p < 0.05) in the diffusing capacity for carbon monoxide.\n Though based on a small group of patients, the present findings suggest that in patients with pulmonary sarcoidosis of stage II and minor functional impairment, inhalation of high doses of BDP as extrafine, peripherally deposited aerosol is associated with a reduction in the number of BAL lymphocytes, in parallel with improvements in other markers of the disease." ]

[ "9893773", "16424410", "1974686", "9438143", "14730657", "9227720", "15598475", "14712884", "10069876", "7503401", "11908511", "17137405", "1892303", "14529100", "11206232", "12197575", "15871441", "11207020", "9759798" ]

[ "Low-dose formoterol Turbuhaler (Oxis) b.i.d., a 3-month placebo-controlled comparison with terbutaline (q.i.d.).", "Formoterol, 24 microg bid, and serious asthma exacerbations: similar rates compared with formoterol, 12 microg bid, with and without extra doses taken on demand, and placebo.", "Long-term efficacy of formoterol compared to salbutamol.", "Long-term effects of formoterol and salbutamol on bronchial hyperreactivity and beta-adrenoceptor density on lymphocytes in children with bronchial asthma.", "Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma.", "Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators.", "Efficacy, tolerability, and effect on asthma-related quality of life of formoterol bid via multidose dry powder inhaler and albuterol QID via metered dose inhaler in patients with persistent asthma: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study.", "Efficacy and tolerability of formoterol Turbuhaler in children.", "Sustained bronchoprotection, bronchodilatation, and symptom control during regular formoterol use in asthma of moderate or greater severity. The Canadian FO/OD1 Study Group.", "Inhaled formoterol dry powder in the treatment of patients with reversible obstructive airway disease. A 3-month, placebo-controlled comparison of the efficacy and safety of formoterol and salbutamol, followed by a 12-month trial with formoterol.", "Is the increase in bronchial responsiveness or FEV1 shortly after cessation of beta2-agonists reflecting a real deterioration of the disease in allergic asthmatic patients? A comparison between short-acting and long-acting beta2-agonists.", "Efficacy and safety of budesonide and formoterol in one pressurised metered-dose inhaler in adults and adolescents with moderate to severe asthma: a randomised clinical trial.", "A three-month comparison of twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma.", "Formoterol delivered via the dry powder Aerolizer inhaler versus albuterol MDI and placebo in mild-to-moderate asthma: a randomized, double-blind, double-dummy trial.", "A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler.", "One-year efficacy and safety of inhaled formoterol dry powder in children with persistent asthma.", "Efficacy and safety of formoterol delivered via a new multidose dry powder inhaler (Certihaler) in adolescents and adults with persistent asthma.", "Comparison between formoterol 12 microg b.i.d. and on-demand salbutamol in moderate persistent asthma.", "A 3-month comparison of formoterol with terbutaline via turbuhaler. A placebo-controlled study." ]

[ "This study compared the efficacy of a low dose of formoterol Turbuhaler 6 micrograms b.i.d. (F) with that of terbutaline 0.5 mg q.i.d. (T), and placebo (P) from Turbuhaler. After a 2-week run-in, 397 adults with mild to moderate asthma were randomly allocated to one of the treatments for 12 weeks. During run-in, the mean morning peak expiratory flow (PEF) was 360 (F), 368 (T) and 367 1 min-1 (P). F was better than T (P = 0.014) and P (P = 0.0001) in improving morning PEF [mean changes from run-in: 20 (F), 9 (T), and 21 min-1 (P)]. F was statistically significantly more effective than either T or P in reducing asthma symptoms. F gave also statistically significantly higher evening PEF and less use of rescue medication than P. Bronchodilator response to study drugs and additional 1.25 mg terbutaline was similar before and after the 12-week treatment period. There were no adverse effects of clinical relevance. In conclusion, formoterol Turbuhaler, 6 micrograms b.i.d. was more effective in improving PEF and offered better asthma control than either terbutaline Turbuhaler, 0.5 mg q.i.d. or placebo. Regular use of formoterol did not reduce the bronchodilator response to additional terbutaline. There were no clinically relevant adverse effects.", "The primary objective was to determine whether high-dose formoterol, 24 mug bid, was associated with more asthma exacerbations compared with lower formoterol doses in patients with stable persistent asthma. Serious asthma exacerbations (life threatening or requiring hospitalization) were the primary end point. Secondary end points included significant exacerbations requiring systemic corticosteroids, all exacerbations, and changes in FEV1.\n In a multicenter, placebo-controlled, parallel-group study, patients were randomized to 16 weeks of treatment with formoterol, 24 microg bid; formoterol, 12 microg bid, with up to two additional 12-microg doses daily on demand for worsening symptoms (12 microg bid plus on demand); formoterol, 12 microg bid; or placebo. The formoterol 12-microg-bid plus on-demand regimen was administered open label, while the other three regimens were double blind.\n Outpatient clinics.\n A total of 2,085 patients aged > or = 12 years with stable, persistent asthma were enrolled and treated; 65% (n = 1,347) received regular concomitant antiinflammatory therapy during the study.\n Nine patients had respiratory-related serious adverse events (SAEs) requiring hospitalization: two patients (0.4%) in the 24-microg-bid group; one patient (0.2%) in the 12-microg-bid plus on-demand group; five patients (0.9%) in the 12-microg-bid group; and one patient (0.2%) in the placebo group. All of these events were asthma related, except for two SAEs in the 12-microg-bid group that were later considered not to be asthma related by independent reviewers who were not associated with the conduct of the study. The proportions of patients with significant asthma exacerbations (requiring systemic corticosteroids) were similar in the 24-microg-bid group (6.3%, 33 of 527 patients), 12-microg-bid group (5.9%, 31 of 527 patients) and placebo group (8.8%, 45 of 514 patients) and lower in the 12-microg-bid plus on-demand group (4.4%, 23 of 517 patients; p = 0.0057 vs placebo). All treatments were well tolerated. All formoterol treatment regimens had a significant effect on FEV1 measured 2 h after dose during the study (p < 0.0001 vs placebo); and on predose trough FEV1 measured at all visits after baseline (p < 0.002 vs placebo).\n Treatment with formoterol, 24 microg bid, was not associated with an increase in serious asthma exacerbations compared with the lower formoterol doses or placebo.", "In a randomized, double-blind, between-patient, multicenter study in 301 patients with ROAD, the efficacy and tolerability of the new long-acting selective beta 2-sympathicomimetic drug formoterol (12 micrograms inhalation b.i.d.) was compared with salbutamol (200 micrograms inhalation q.i.d.). There was no statistically significant (s.s.) difference in acute reversibility and long-term efficacy of both drugs, measured by the point in time of expected maximal effect. However, formoterol had a highly s.s. longer duration of action than salbutamol, as shown by peak expiratory flow (PEF) measurements: the overall mean morning PEF in the formoterol group was 341 L/min. 14 h after the last taken dose and in the salbutamol group this measure was 304 L/min 9 h after the last dose. The patients taking formoterol had s.s. less asthma attacks and needed s.s. less rescue medication than those taking salbutamol. In the global assessment of efficacy, formoterol was accepted as being s.s. better (\"very good\" + \"good\": 76%) than salbutamol (\"very good\" + \"good\": 50%). The tolerability of each drug, as reflected by adverse reactions and global assessment, was equally good in both groups. Ninety-one percent of the patients in the formoterol group wanted to receive the same drug again versus 79% in the salbutamol group.", "Long-term treatment with short-acting beta 2-sympathomimetic drugs has recently been suggested to be due to a rise in asthma mortality. This effect has been attributed to an increase in bronchial hyperreactivity, a desensitization of beta 2-adrenoceptors and/or a rebound effect after cessation of the therapy. Formoterol, a new long-acting beta 2-symathomimetic drug, has been reported to possess not only bronchodilatation but also antiinflammatory effects. The aim of the present study was to investigate whether long-term effects of salbutamol and/or formoterol could deteriorate asthma management. Therefore, in a trial lasting 90 days, we evaluated the effects of the two drugs on lung function, on the protection they provided against inhalative provocation with histamine, and on tachyphylaxis as monitored by the beta-adrenergic density on mononuclear leukocytes (MNL). Two groups of 11 children each with stable asthma were treated with daily doses of either 4 x 200 micrograms salbutamol or 2 x 24 micrograms formoterol in monotherapy. The lung function was measured six times during the trial period, on day 1, and on day 90, before and after inhaling the drug and at all investigations both with and without histamine provocation. In both groups, the bronchodilatory effect of either formoterol or salbutamol remained constant. The lung function values before and after drug inhalation (specific airway resistance sRAW, forced expiration volume FEV1, vital capacity VC) did not alter significantly. After histamine provocation, the protection was more pronounced in the formoterol group. No changes in the beta-adrenoceptor density on MNL and no significant side effects were seen throughout the trial period. We therefore conclude that formoterol protects significantly better against the bronchial challenge with histamine than does salbutamol. Both drugs did not deteriorate the lung function in asthmatic children. In addition, there was no evidence that long-term treatment leads to a desensitization of beta 2-sympathomimetic effects.", "This double-blind, placebo-controlled, randomized, parallel-group, multicenter study was conducted in 302 children aged 6-11 years with asthma not optimally treated with inhaled corticosteroids alone. Patients continued with their existing dose of inhaled corticosteroids and in addition received placebo, formoterol 4.5 microg or formoterol 9 microg b.i.d., for 12 weeks (all delivered via Turbuhaler). Terbutaline was available as reliever medication. The primary efficacy variable was change from baseline in morning peak expiratory flow (PEF); secondary efficacy variables included forced expiratory volume in 1 sec (FEV(1)), serial PEF measured over 12 hr, evening PEF, asthma symptom score, and quality of life. Compared with placebo, formoterol 4.5 microg and 9 microg improved morning PEF by 8 l/min (P = 0.035) and 11 l/min (P = 0.0045), respectively. Evening PEF and FEV(1) were also significantly increased compared with placebo, with no statistically significant difference between formoterol doses. Lung-function improvements compared with placebo were greater in the middle of the day. Twelve-hour average serial PEF after 3 months increased by 24 l/min (95% CI, 9, 39 l/min) in the formoterol 9-microg group, and by 14 l/min (95% CI, 0, 29 l/min) in the formoterol 4.5-microg group. The incidence of severe exacerbations in both formoterol groups was numerically lower than in the placebo group, indicating that formoterol may have the potential to improve exacerbation control in children. Both formoterol doses were well-tolerated, and tolerance to the drug's bronchodilator effect was not observed. Formoterol provided sustained improvements in lung function and was well-tolerated in children with asthma suboptimally treated with inhaled corticosteroids alone.\n Copyright 2004 Wiley-Liss, Inc.", "The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma.\n In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout.\n One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively).\n Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.", "Inhaled beta(2)-agonists are widely used in asthma treatment. The design limitations of pressurized metered dose inhalers (pMDIs) have prompted the development of dry powder inhalers (DPIs) for the delivery of asthma medications.\n The goal of this study was to evaluate the efficacy, tolerability, and effect on asthma-related quality of life (QOL) of a long-acting beta(2)-adrenoreceptor agonist, formoterol, delivered via multidose DPI, compared with albuterol delivered via pMDI or placebo in adolescents and adults with persistent asthma.\n This multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was conducted in outpatient clinics at 18 US centers. Adolescents and adults with persistent asthma received formoterol 10 pg BID via multidose DPI, albuterol 180 microg QID via pMDI, or placebo for 12 weeks. The primary efficacy variable was the 12-hour AUC of forced expiratory volume in 1 second (FEV(1)) after 12 weeks treatment. Secondary efficacy variables included asthma-related QOL, asthma symptom scores, rescue medication use, and other pulmonary function measures.\n A total of 239 patients (147 females, 92 males; age range, 13-85 years) with persistent asthma were enrolled (formoterol, n = 80; albuterol, n = 79; placebo, n = 80). Formoterol delivered via the multidose DPI resulted in clinically relevant and statistically significant increases in 12-hour AUC of FEV(1) after 12 weeks of treatment compared with albuterol pMDI and placebo (P < 0.019 and P < 0.001, respectively). Asthma-related QOL (total score) was significantly improved with formoterol treatment compared with placebo (P < 0.015). Nocturnal asthma symptom scores significantly improved with formoterol compared with albuterol and placebo (P < 0.001 and P < 0.003, respectively) and rescue medication use was significantly less with formoterol compared with albuterol and placebo (P < 0.004 and P < 0.002, respectively). Treatment with formoterol was well tolerated.\n In this study of adolescents and adults with persistent asthma, 12 weeks of treatment with formoterol 10 microg BID delivered via a multidose DPI provided significantly greater 24-hour bronchodilation compared with albuterol and placebo and resulted in significant improvements in asthma-related QOL compared with placebo. Formoterol was well tolerated in these patients.", "A randomised, double-blind trial was undertaken to investigate the efficacy and tolerability of formoterol Turbuhaler in children with mild to moderate asthma. After a two-week run-in, 248 children aged 6-17 years were randomised to receive formoterol 4.5 and 9 pmicro b.i.d. or placebo for 12 weeks. Morning PEF (primary variable), was significantly improved versus placebo only in the formoterol 9 pmicro b.i.d. group (13 l/min, 95% CCI 1.9, 24.2%; p = 0 .02). Both formoterol 4.5 and 9 pmicro significantly increased the pre-bronchodilator FEV1 by 5.2-6.7% (p < 0 .05) and reduced use of daytime relief medication versus placebo (p < 0 .05). Formoterol 9 pmicro significantly reduced night-time reliever use and awakenings due to asthma versus placebo (p < 0.05). Both doses of formoterol were as well tolerated as placebo. In conclusion, formoterol 4.5 and 9 micro b.i.d. is effective and well tolerated as maintenance therapy in children with mild to moderate asthma.", "Recent studies have raised concern that regular inhalation of beta2 -agonists may cause a worsening of asthma control compared with on-demand dosing regimens.\n The objective of this study was to compare the effect of twice daily formoterol (Foradil), 4 times daily albuterol, and on-demand albuterol on bronchial hyperresponsiveness (BHR), lung function measurements, symptoms, and other indicators of disease control over 6 months inpatients with asthma of moderate or greater severity receiving concomitant inhaled corticosteroids. We also looked for occurrence of rebound BHR on discontinuation of treatment.\n This was a multicenter, parallel-group, double-blind, clinical trial. Methacholine PC20 was the primary outcome variable. Other outcome variables included symptom scores, use of rescue medication, morning peak expiratory flow (PEF), serial FEV1 measurements, and asthma exacerbations.\n Of the 271 randomized patients, 217 completed the study. Formoterol was significantly superior to on-demand albuterol with regard to methacholine PC20, FEV1, PEF, symptom scores, and use of rescue medication at each measured time point/interval. Regular albuterol was superior to on-demand albuterol with regard to PC20 and FEV1, but not PEF or various clinical scores. After a small drop in the magnitude of bronchoprotection and bronchodilatation occurring shortly after randomization, there was no evidence of progressive tolerance to either regular treatment for any of the measured variables or of rebound increase in BHR 2 days after the end of treatment. The formoterol group had the lowest number of exacerbation days, as defined by high intake of rescue bronchodilator and/or symptom scores, whereas the number of exacerbations requiring increased corticosteroid coverage was similar in the 3 groups.\n In patients with asthma of moderate or greater severity receiving inhaled corticosteroids, formoterol taken twice daily resulted in superior bronchoprotection, bronchodilatation, and clinical control compared with on-demand albuterol over 6 months. Four times daily albuterol was superior to on-demand albuterol for only some of the end points. Progressive tolerance and a rebound increase in BHR on discontinuation of beta-agonists were not found", "Inhaled formoterol is a potent selective beta 2-agonist with rapid onset and at least 12-h duration of bronchodilation. The aim of the study was to compare the bronchodilating effect of inhaled formoterol dry powder (dp) 12 micrograms b.i.d. with salbutamol dp 400 micrograms q.i.d. and placebo in patients with reversible obstructive airway disease (ROAD). The study design consisted of a closed 12-week double-blind, placebo-controlled, multicenter trial followed by an open noncomparative, multicenter, 12-month follow-up trial, in which the tolerability of formoterol dp was assessed. A total of 304 patients (146 men, 158 women) aged 18-79 years, ill during 0.1-64 years, were randomized. No demographic or baseline differences were found among the different treatment groups. The bronchodilating effect of formoterol, assessed by morning premedication PEFR, was significantly superior to placebo (P < 0.0001) and salbutamol (P < 0.0001). Efficacy was maintained during the open follow-up study with 12 micrograms b.i.d. in most of the patients. A few patients, however, needed 24 micrograms b.i.d. to control their ROAD. Formoterol 12 micrograms b.i.d. significantly reduced morning and evening asthma symptoms and sleep disturbances, and reduced significantly the need for rescue medication. The tolerability of the three treatment groups was comparable. In conclusion, formoterol 12 micrograms dp b.i.d. was significantly superior to both salbutamol 400 micrograms dp q.i.d. and placebo, and reduced asthma symptoms significantly. Overall, formoterol showed a tolerability profile comparable to that of salbutamol, and no tachyphylaxis was observed during 1 year of treatment.", "Regular use of beta2-agonists might result in increased bronchial hyper-responsiveness (BHR) and decreased forced expiratory volume in 1 sec (FEV1). It has been suggested that these possible detrimental effects are not a real deterioration of the disease, but that it might be only a transient (rebound) effect shortly after discontinuing this regular use. Moreover, these effects are thought to occur especially during short-acting and not during long-acting beta2-agonists use. The aim of this study was to invest gate whether a rebound effect (a pharmacological deterioration effect diminishing after several hours) in FEV1 and PC20 (concentration of histamine causing a 20% fall in FEV1 with regard to baseline) occurred after cessation of regular use of beta2-agonists, and whether this occurred both after short-acting and long-acting beta2-agonists. Allergic asthmatic patients (n = 134) were randomly allocated to the use of a short-acting (salbutamol), a long-acting beta2-agonist (formoterol) or placebo for 12 weeks (double-blind, double-dummy). No other asthma medication was allowed, including inhaled corticosteroids. At the start and every 4 weeks later FEV and PC20 were measured, each time at least 12 h after the last doses of study medication, which is in the possible rebound period. To investigate whether a (transient) rebound effect occurred, parameters were additionally measured at least 72 h later after discontinuation of the study medication. After 12 weeks of short-acting beta2-agonist use, a drop was seen in FEV1 from 85.6 (+/- 2.21)% predicted to 78.8 (+/- 2.9)% predicted, measured 15 h (median) after the last doses of medication. This was significantly different compared to placebo. When measured 168 h (median) later FEV1 recovered to 85.5 (+/- 2.4)% predicted, comparable to baseline. PC20 decreased with -1.17 (+/- 0.44) doubling dose after 12 weeks of short-acting beta2-agonist use, measured 15 h after the last doses of medication, which was significantly different compared to placebo. However, 168 h later PC20 recovered slightly with +0.55 (+/- 0.34) doubling dose, but this value was still lower compared to placebo. In contrast, during long-acting beta2-agonist and placebo use no significant changes were seen. In conclusion, the use of short-acting beta2-agonists resulted in a transient (rebound) effect in FEV while the effects on PC20 may point to a real deterioration of the disease. Long-acting beta2-agonist and placebo use showed no changes. We conclude that a mono-therapy of short-acting and not of long-acting beta2-agonists might have deleterious effects in asthma.", "Inhaled corticosteroids (ICSs) are the preferred maintenance therapy for adults and children with mild, moderate and severe persistent asthma, with the addition of a long-acting beta(2)-adrenoceptor agonist to ICS therapy recommended for patients with moderate or severe persistent asthma. The efficacy and safety of the combination of budesonide and formoterol delivered via dry powder inhaler (DPI) is well documented.\n To compare the efficacy and safety of budesonide/formoterol pressurised metered-dose inhaler (budesonide/formoterol pMDI; Symbicort pMDI, AstraZeneca LP, Wilmington, DE, USA) with budesonide pMDI (Pulmicort pMDI, Astra [corrected] Zeneca, Lund, Sweden), formoterol DPI (Oxis Turbuhaler, AstraZeneca, Lund, Sweden), budesonide plus formoterol in separate inhalers (budesonide pMDI + formoterol DPI) and placebo.\n This was a 12-week randomised, double-blind, double-dummy, placebo-controlled study.\n This multicentre study was conducted in the respiratory specialty clinical practice setting.\n The study included 596 patients > or =12 years of age with moderate to severe persistent asthma previously receiving ICSs.\n After 2 weeks on budesonide pMDI 80 microg x two inhalations (160 microg) twice daily, patients received budesonide/formoterol pMDI 160 microg/4.5 microg x two inhalations (320 microg/9 microg); budesonide pMDI 160 microg x two inhalations (320 microg) + formoterol DPI 4.5 microg x two inhalations (9 microg); budesonide pMDI 160 microg x two inhalations (320 microg); formoterol DPI 4.5 microg x two inhalations (9 microg); or placebo twice daily.\n There were two prespecified primary efficacy variables: mean change from baseline in morning predose forced expiratory volume in 1 second (FEV(1)), obtained approximately 12 hours after the most recent administration of study medication at home and immediately before the next administration of study medication at the clinic; and mean change from baseline in 12-hour FEV(1), assessed as the average change in FEV(1) from serial spirometry over the 12-hour period after administration of the morning dose of study medication at the clinic.\n Mean changes from baseline in morning predose FEV(1) at end of treatment were greater (p < or = 0.049) with budesonide/formoterol pMDI (0.19L) versus budesonide pMDI (0.10L), formoterol DPI (-0.12L) and placebo (-0.17L). Mean changes from baseline in 12-hour FEV(1) were greater (p < or = 0.001) with budesonide/formoterol pMDI after 1 day (0.37L), 2 weeks (0.34L) and at end of treatment (0.37L) versus budesonide pMDI (0.11, 0.15 and 0.15L) and placebo (0.09, -0.03 and -0.03L), and after 2 weeks and at end of treatment versus formoterol DPI (0.19 and 0.17L). Fewer (p < or = 0.025) patients receiving budesonide/formoterol pMDI versus monoproducts or placebo met worsening asthma criteria. Results were similar in the budesonide/formoterol pMDI group and the budesonide pMDI + formoterol DPI group on all measures. All treatments were well tolerated with similar safety profiles.\n In this population, twice-daily budesonide/formoterol pMDI provides asthma control significantly greater than the monocomponents or placebo and comparable with budesonide pMDI + formoterol DPI. Safety profiles were similar for all treatments.", "We compared the efficacy of inhaled formoterol, a long-acting beta 2-agonist, with inhaled albuterol in 145 stable adult asthmatics in a 12-wk multicenter trial. Patients were allocated in randomized double-blind fashion to maintenance therapy with either formoterol 12 micrograms twice a day or albuterol 200 micrograms four times a day in addition to their other asthma medications. Patients were allowed to use \"rescue\" 100-micrograms albuterol puffs on an as-needed basis. Mean baseline FEV, in the morning before bronchodilator was 2.14 +/- 0.76 L and 1.98 +/- 0.71 L for the formoterol and albuterol groups, respectively, these values being used as baseline covariates in subsequent analysis of predrug and postdrug FEV1. Measured at each clinic visit, morning predrug FEV1 rose significantly with formoterol treatment and was significantly greater at all visits than in the albuterol group, the greatest difference being in Week 8 (2.40 +/- 0.77 versus 1.92 +/- 0.66 L, p less than 0.001). Morning FEV1 30 min postdrug was significantly higher in the formoterol group at Weeks 2 and 8, the trend not reaching statistical significance at other times. Diurnal variation in prebronchodilator peak flow rates was significantly reduced in the formoterol group throughout the trial (17 versus 42 L/min at Week 12, p less than 0.0001). The number of asthma episodes per week was significantly less in the formoterol group during Weeks 4, 8, and 12 as were the number of sleep disruptions during Weeks 2, 4, 6, 8, and 12. Significantly more rescue albuterol was required in the albuterol group by Week 2 and throughout the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS)", "The objectives of this study were to compare the efficacy and tolerability of twice-daily formoterol dry powder 12 microg and 24 microg (Foradil) delivered via Aerolizer inhaler with four times daily albuterol (salbutamol) 180 microg delivered via metered dose inhaler (MDI) and placebo. A total of 554 adolescents and adults (ages 12-75 years) with mild-to-moderate asthma were randomized to this 12-week, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study. Twelve-hour spirometry measurements were taken at weeks 0, 4, 8, and 12. A total of 484 patients completed the study (122, 116, 127, and 119 given formoterol 12 microg, formoterol 24 microg, albuterol, and placebo, respectively). For the primary efficacy variable, the forced expiratory volume in 1 second (FEV1), both formoterol 12 microg and 24 microg were statistically superior to placebo at all time points on all test days (p < or = 0.017) and to albuterol at most time points on all test days (p < or = 0.001). The onset of improvement in FEV1 was rapid, with 15% increase within 5 min in 57%, 71%, and 65% of formoterol 12 microg, formoterol 24 microg, and albuterol patients, respectively. Formoterol was also superior to placebo and albuterol in terms of secondary efficacy variables: FEV1 area under the curve, percentage of predicted FEV1, forced vital capacity and forced expiratory flow, asthma symptom scores, and peak expiratory flows. In conclusion, both formoterol doses were superior to placebo in all lung function measurements. Overall, compared with albuterol, both formoterol doses produced superior bronchodilation. Formoterol and albuterol were safe and well-tolerated.", "Formoterol is a beta2-adrenergic agent which, when inhaled, produces rapid and long-lasting bronchodilatation.\n The aim of this study was to compare the efficacy, safety, and tolerability of formoterol powder for inhalation delivered via the Aerolizer device with placebo and with albuterol delivered via metered-dose inhaler in patients with mild to moderate persistent asthma.\n In a multicenter, double-blind, parallel-group study, 541 patients were randomized at 26 trial sites to receive either formoterol, 12 microg twice daily; formoterol, 24 microg twice daily; albuterol, 180 microg four times daily; or a placebo for 12 weeks. The effects of each treatment on lung function, asthma symptoms, and frequency of rescue albuterol use were evaluated. Adverse effects and clinical laboratory parameters were also evaluated.\n The bronchodilatory effects of formoterol were rapid in onset and persisted for 12 hours. Both formoterol doses were more effective than placebo and albuterol for objective measures of lung function. Morning and evening peak expiratory flow rates were more improved with formoterol, and formoterol provided significantly greater improvements in asthma symptom scores compared with both albuterol and placebo. Overall, patients taking formoterol used significantly less rescue medication than did those taking albuterol or placebo. Nocturnal awakenings occurred less often with formoterol than with placebo or albuterol. The therapeutic effects of formoterol were maintained over the entire 12 weeks of treatment. Adverse events were similar for all treatment groups, and clinical laboratory data were unremarkable.\n Rapid-onset, long-acting formoterol, administered via the Aerolizer inhaler, is an effective and safe treatment for patients with mild to moderate persistent asthma.", "The long-term efficacy and safety of formoterol dry powder capsules for inhalation in pediatric asthma have not previously been evaluated.\n We examined the effectiveness of inhaled formoterol over a period of 12 months in asthmatic children who were still symptomatic despite anti-inflammatory treatment.\n After a run-in period, 518 patients (5 to 12 years old) were randomized in a double-blind manner to receive 12 or 24 microg formoterol dry powder (Foradil, Novartis Pharma AG, Basel, Switzerland) or placebo twice daily for 12 months. The drug was administered by inhaler (Aerolizer, Novartis Pharma AG) and was given in addition to their anti-inflammatory treatment. The primary variable was the area under the curve for forced expiratory volume in 1 second measured over 12 hours after the morning dose of study medication.\n The area under the curve for forced expiratory volume in 1 second after the first dose of treatment and after 3 and 12 months of treatment was significantly greater for patients receiving formoterol 12 microg and 24 microg than for patients receiving placebo (all P < or = 0.0062). Compared with placebo, both doses of formoterol significantly improved morning and evening premedication peak expiratory flow rate (all P < 0.001). In the group treated with formoterol 24 microg, median symptom score and median dose of rescue medication at night were lower than during the run-in period, whereas the opposite occurred in the placebo group. The incidence of hospitalizations for asthma was higher in the formoterol groups than in the placebo group.\n Our results indicate that, in asthmatic children who are still symptomatic despite anti-inflammatory therapy, the addition of formoterol consistently improves airflow obstruction and nocturnal symptoms and reduces the use of rescue medication. However, this treatment requires close disease monitoring to detect early signs of acute exacerbation.", "Our objective was to compare the efficacy and safety of formoterol (Foradil) delivered via a novel multidose dry powder inhaler (Certihaler) with placebo and albuterol [pressurized metered-dose inhaler (pMDI)], in patients with persistent asthma. After a 2-week run-in phase, 265 patients (13-81 years) previously treated with regular/PRN bronchodilators for persistent asthma were randomized to 12 weeks' double-blind treatment with formoterol 10 microg BID via Certihaler (n = 86), albuterol 180 microg QID via pMDI (n = 88) or placebo (n = 91). The primary efficacy variable was 12-hour AUC of FEV1 after 12 weeks' treatment. Secondary efficacy variables included peak expiratory flow (PEF), rescue bronchodilator medication use, asthma-related quality of life (Juniper Mini Asthma Quality of Life Questionnaire), and asthma symptom scores. Formoterol via the Certihaler had an onset of action within 5 minutes and was associated with a clinically relevant and statistically significant increase in 12-hour AUC of FEV1 after 12 weeks' treatment compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Average PEF was significantly superior for formoterol compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Compared with placebo, rescue albuterol use during the study was significantly lower for formoterol (p < 0.01) and was accompanied by a trend toward an improvement in asthma-related quality of life (QoL). Asthma symptom scores improved to a similar extent for all treatment groups. Treatment with formoterol via Certihaler was well tolerated. Formoterol 10 microg BID, delivered via the novel Certihaler device, is well tolerated and provides rapid, long-lasting, and clinically superior bronchodilation to placebo and albuterol via pMDI in patients with persistent asthma.", "Inhalation of on-demand salbutamol (ODS) several times daily is sometimes the only beta2-agonist prescribed in moderate persistent asthma, whereas a long-acting beta2-agonist should be added. This trial aimed to compare the efficacy of formoterol dry-powder capsule 12 microg b.i.d. (Foradil) and ODS in patients with moderate persistent asthma treated with inhaled corticosteroids, in the conditions of real practice. Two hundred and fifty-nine patients were randomized (formoterol; 130; ODS: 129) in this open, parallel-group trial. The mean increases in morning peak expiratory flow (PEF primary variable) and evening PEF over the 3-month treatment period were statistically significantly higher with formoterol: +25.7 and +24.1 l min(-1), respectively vs. +4.5 and +0.5 l min(-1) respectively with ODS. The increase in FEV1 was statistically significantly higher with formoterol at months 1 and 3. Formoterol reduced the use of salbutamol as rescue medication by two-thirds. The percentages of symptom-free days and nights statistically significantly increased with formoterol (+20% and +33% respectively), but did not significantly change with ODS. Clinically relevant and statistically significant improvement in the mean total score of the St George's Hospital Respiratory Questionnaire was observed in the formoterol group. Adverse events were similar in the two groups. The results show that treatment with formoterol has significant advantages over ODS in patients with moderate persistent asthma.", "Oxis Turbuhaler is a new dry powder formulation of long-acting beta2-agonist formoterol. This study compared the efficacy and safety of regular use of the long-acting beta2-agonist formoterol and the short-acting terbutaline for 3 months in patients with asthma.\n After 1-week run-in, 343 patients received either formoterol 12 microg bid (F) (delivered dose of 9 microg), terbutaline 500 microg qid (T) or placebo qid, in a parallel-group, double-blind, randomized manner. They had a mean of 61% of predicted forced expiratory volume in 1 second (FEV1) and a mean reversibility of 26%. Eighty-nine percent used inhaled corticosteroids.\n During run-in mean morning peak expiratory flow (PEF L/min) for F was 366 and 348 for T, and 344 for placebo (P). The F group improved morning PEF significantly compared with P (P = .0022) and T (P = .0001). Changes from run-in were + 18, -1.5, and +5 L/min after F, T, and P, respectively. The F group was statistically significantly better than P and T in increasing evening PEF and in reducing night-time asthma. The F and T statistically significantly reduced the use of rescue medication compared with P. The bronchodilating response to the study drug and to an additional 1.25 mg terbutaline was of the same magnitude before and throughout the study. No statistically significant treatment-by-time interaction was observed (P > .20). There were no adverse effects of clinical relevance.\n Formoterol Turbuhaler, 12 microg bid, was more effective than terbutaline Turbuhaler, 0.5 mg qid, and placebo. Regular use of formoterol or terbutaline did not significantly influence the response to additional inhalation of terbutaline." ]

[ "1407926", "7120214", "10580682", "9824184", "9916961", "3048103", "6145635", "9387512", "1319808", "331952", "10601925", "8333483", "6708033", "1530035", "2206069", "3548382", "8238157", "2276652", "12066082", "4073155" ]

[ "A prospective comparison of terbutaline and magnesium for tocolysis.", "A comparison of magnesium sulfate and terbutaline for the arrest of premature labor. A preliminary report.", "Prevention of preterm delivery: nifedipine or magnesium sulfate.", "A comparative study of ketorolac (Toradol) and magnesium sulfate for arrest of preterm labor.", "Randomized comparison of intravenous nitroglycerin and magnesium sulfate for treatment of preterm labor.", "Efficacy and side effects of magnesium sulfate and ritodrine as tocolytic agents.", "The use of ritodrine and magnesium sulfate in the arrest of premature labor.", "[Treatment of preterm labor with ritodrine].", "[Magnesium sulfate in prevention of preterm labor].", "A comparison of magnesium sulfate and alcohol for the prevention of premature labor.", "Oral nicardipine versus intravenous magnesium sulfate for the treatment of preterm labor.", "Efficacy and safety of indomethacin compared with magnesium sulfate in the management of preterm labor: a randomized study.", "Comparison of magnesium sulfate, terbutaline and a placebo for inhibition of preterm labor. A randomized study.", "Evaluation of maternal fluid dynamics during tocolytic therapy with ritodrine hydrochloride and magnesium sulfate.", "Randomized investigation of magnesium sulfate for prevention of preterm birth.", "Magnesium sulfate and ritodrine hydrochloride: a randomized comparison.", "Efficacy and safety of nifedipine versus magnesium sulfate in the management of preterm labor: a randomized study.", "[Tocolytic therapy with magnesium sulfate and terbutaline for inhibition of premature labor].", "Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants.", "A comparison of ritodrine, terbutaline, and magnesium sulfate for the suppression of preterm labor." ]

[ "To compare the tocolytic efficacy and side effects of parenteral and oral magnesium and terbutaline.\n Ninety-eight patients in labor between 23-35 weeks were prospectively entered into a controlled trial of intravenous and oral magnesium versus subcutaneous and oral terbutaline. Tocolytic effectiveness was judged by delay of delivery for 48 hours or 1 week, and to 37 weeks or more. The need to change therapy to the alternate drug was identified, as were side effects. Entrance characteristics of the population, initial pelvic examination, and concomitant infection or cervicovaginal isolates were noted. Outcomes included gestational age at delivery, birth weights, and Apgar scores. Outcome analysis was based on initial tocolytic therapy.\n Significantly more patients in the magnesium group delivered at 37 weeks or more: 34 of 46 versus 27 of 52 (P < .05). No significant differences were found for delivery by 48 hours or 1 week. The interval between treatment and delivery was greater for magnesium: 7.1 +/- 3.9 versus 5.0 +/- 3.2 weeks (P < .005). Failure to achieve 37 completed weeks was more often due to obstetric complications than to preterm labor itself. Tocolytic effectiveness was reduced if secondary therapy or re-treatment was required or if the patient had cervical dilatation of 3 cm or greater. Infectious complications were common but were not associated with tocolytic effectiveness. Side effects were more noticeable with oral magnesium and subcutaneous terbutaline.\n For short-term tocolysis, no significant difference was found between magnesium and terbutaline. Magnesium was associated with a higher term delivery rate. Idiopathic preterm labor accounted for only a small part of the overall prematurity in the study population.", "Intravenous magnesium sulfate and terbutaline were compared as treatments for premature labor. A successful treatment was the arrest of labor for 24 hours. Early treatment was essential for successful management of premature labor. In this study, magnesium sulfate and terbutaline were equally effective in controlling premature labor. Whereas terbutaline was associated with significant alterations in diastolic blood pressure, maternal pulse, fetal heart rate and potassium concentration, magnesium sulfate was not. Magnesium sulfate holds promise as a tocolytic agent, and further clinical study of it is warranted.", "to establish the efficacy and safety of nifedipine and magnesium sulfate in arresting preterm labor.\n seventy-four patients with singleton pregnancies at 23-36 weeks in preterm labor, were selected randomly to receive either oral nifedipine or intravenous magnesium sulfate.\n both drugs had similar tocolytic efficacy and side effects while nifedipine was faster than magnesium sulfate in arresting uterine contractions (4.8 +/- 4.23 vs. 2.98 +/- 3.03 h) P = 0.04.\n this data suggests that oral nifedipine with the same efficacy, side effects and faster action could be a suitable and more convenient alternative to intravenous magnesium sulfate in arresting preterm labor.", "We evaluated the efficacy and safety of ketorolac (Toradol).\n In this prospective trial, 88 women in confirmed preterm labor at < or =32 weeks' gestation were randomized to receive magnesium sulfate given as an initial 6 g intravenous bolus followed by continuous infusion therapy (2 to 6 g/hr) or intramuscularly administered ketorolac (60 mg loading dose) followed by 30 mg every 6 hours for a maximum of 24 hours.\n The study groups were similar with respect to age, parity, cervical status, and gestational age on admission. Ketorolac was more rapid (2.71 hr+/-2.16) in the arrest of preterm labor than was magnesium sulfate (6.22 hr+/-5.65). No patient required discontinuance of either drug due to adverse effects. There was no difference in the incidence of neonatal complications between the two groups.\n In gestations with preterm labor at <32 weeks, ketorolac appears to be an appropriate first-line tocolytic agent.", "To compare the safety and efficacy of high-dose intravenous (IV) nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm labor.\n Thirty-one women with preterm labor before 35 weeks' gestation were assigned randomly to IV magnesium sulfate or IV nitroglycerin for tocolysis. Preterm labor was defined as the occurrence of at least two contractions in 10 minutes, with cervical change or ruptured membranes. Acute tocolysis was defined as tocolysis for up to 48 hours. Magnesium sulfate was administered as a 4-g bolus, then at a rate of 2-4 g/h. Nitroglycerin was administered as a 100-microg bolus, then at a rate of 1- to 10-microg/kg/min. The primary outcome measure was achievement of at least 12 hours of successful tocolysis.\n Thirty patients were available for analysis. There were no significant differences in gestational age, cervical dilation, or incidence of ruptured membranes between groups at the initiation of tocolysis. Successful tocolysis was achieved in six of 16 patients receiving nitroglycerin, compared with 11 of 14 receiving magnesium sulfate (37.5 versus 78.6%, P = .033). Tocolytic failures (nitroglycerin versus magnesium sulfate) were due to persistent contractions with cervical change or rupture of previously intact membranes (five of 16 versus two of 14), persistent hypotension (four of 16 versus none of 14), and other severe side effects (one of 16 versus one of 14). Maternal hemodynamic alterations were more pronounced in patients who received nitroglycerin, and 25% of patients assigned to nitroglycerin treatment had hypotension requiring discontinuation of therapy.\n Tocolytic failures were more common with nitroglycerin than with magnesium sulfate. The hemodynamic alterations noted in patients receiving nitroglycerin, including a 25% incidence of persistent hypotension, might limit the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor.", "Ritodrine as the first-line drug in the treatment of established preterm labor has been supplanted in some centers by magnesium sulfate. To assess the relative efficacy and rates of side effects of these two agents, 120 patients were randomly assigned to receive one of these two drugs. Patients were included if they had intact membranes and met strict criteria for the definition of labor. In both groups excellent outcome was achieved, with 96.3% and 92.3% of patients receiving ritodrine and magnesium sulfate, respectively, obtaining a delay in delivery of greater than 48 hours. Side effects were comparable in both groups, although they tended to be more serious in the patients receiving ritodrine. In patients receiving both drugs together, the rate of side effects was 77% without a demonstrable benefit over a single agent. We conclude that ritodrine and magnesium sulfate are tocolytics of comparable efficacy and when used aggressively are highly successful in delaying delivery.", "Sixty-seven cases of premature labor (48 with unruptured and 19 with ruptured membranes) were treated with ritodrine or magnesium sulfate infusion supplemented with oral ritodrine in case of initial success. Both treatment regimens were found effective irrespective of maternal age, parity, ethnic background and number of previous abortions. The study supports the clinical experience indicating that early administration of tocolytic agents is highly successful in arresting premature labor and preventing its dire consequences.", "To investigate the treatment of preterm labor with the beta-adrenergic agonist ritodrine.\n 126 women with preterm labor were randomly assigned to intravenous infusion of ritodrine or magnesium sulfate treatment. Using minimal effective dosage for inhibition of uterine activity, terminating therapy on time, and repeating the i.v. infusion if contraction restarted were the strategy for treatment.\n Ritodrine was significantly more effective both in the treating period for suppression of contraction (2.33 +/- 0.63 hr for initiation of inhibiting uterine activity, 9.38 +/- 3.88 days of accumulative treating period) and prolongation of gestation (4.81 +/- 2.83 wks) than that of the magnesium sulfate (P < 0.001, 0.005 and 0.01 respectively), and had a term labor of 73.44%. There was no serious cardiac and pulmonary complications in the ritodrine group.\n The present study has shown that ritodrine as a tocolytic agent is highly effective for the management of preterm labor and relative safe for mother and fetus.", "To observe the efficacy of magnesium sulfate in the treatment of preterm labor, 65 uncomplicated cases of preterm labor between 28 and 36 weeks of gestation were studied prospectively during Sep. 1988-May 1991. They were divided into two groups randomly. 30 cases were treated with magnesium sulfate and 35 cases with barbiturates or bed rest. The prevention of delivery for at least 48 hours after the initiation of therapy was achieved in 23 of the 30 cases (76.67%) of the magnesium sulfate group and in 3 of the 35 cases (8.57%) in the control group. Delay of more than 7 days was achieved in 17 of the 30 cases (56.67%) and in 2 of the 35 cases (5.71%). The postponement of delivery between the two groups. There was highly significantly difference (P less than 0.01). There was a significant correlation of cervical dilation at the onset of treatment to success of controlling preterm labor. In the magnesium sulfate group, the mean magnesium level to achieve tocolysis was 2.8 +/- 0.35 mmol/L (mean +/- s). The side effects to the mothers, fetus, and the neonates were mild and not prominent.(ABSTRACT TRUNCATED AT 250 WORDS)", "In travenous magnesium sulfate and alcohol were compared as treatments for premature labor. A successful treatment was the absence of contractions for a 24 hour interval. Early treatment was found to be essential for successful management of premature labor. There is a significant correlation of cervical dilatation at the onset of treatment to success at controlling premature labor. There was no statistically significant relation to weeks of gestation or parity to success at controlling premature labor. In this study magnesium sulfate was the better agent for controlling premature labor.", "The aim of this study was to compare the efficacy and safety of oral nicardipine in acute therapy for preterm labor with those of parenteral magnesium sulfate.\n Patients between 24 and 34 weeks' gestation with documented preterm labor were randomly assigned to receive oral nicardipine (n = 57) or intravenous magnesium sulfate (n = 65) as initial tocolytic therapy. Patients in the nicardipine group received a 40-mg loading dose and then 20 mg every 2 hours as needed to stop contractions (total 80 mg). Patients in the magnesium sulfate group received a 6-g bolus followed by 2 to 4 g/h to provide uterine quiescence. Patients could be switched to another tocolytic regimen if they continued to have contractions after 6 hours of therapy. The main outcome variables examined were time to uterine quiescence, time gained in utero, recurrence of preterm labor, failure of tocolysis, and pertinent maternal and neonatal outcomes.\n There were no significant differences in maternal demographic characteristics between the groups. Among patients who responded with uterine quiescence within 6 hours, there was a significant decrease in the time to uterine quiescence in the nicardipine group (P <.01). Patients in the magnesium sulfate group were more likely to have recurrence of preterm labor necessitating further tocolytic attempts (P =.048). The patients in the magnesium sulfate group had more adverse side effects, mainly nausea and vomiting (P =.004). There were no differences in birth weight, estimated gestational age at delivery, or neonatal complications between the 2 groups.\n Oral nicardipine is an effective, safe, and well-tolerated tocolytic agent. In this prospective clinical trial patients randomly assigned to receive oral nicardipine had arrest of preterm labor more rapidly than did those randomly assigned to receive parenteral magnesium sulfate. Patients who received magnesium sulfate were more likely to have adverse medication effects and recurrent preterm labor.", "Our purpose was to evaluate the relative efficacy and safety of indomethacin versus magnesium sulfate in the management of preterm labor in pregnancies < 32 weeks of gestation.\n Eligible patients admitted with singleton pregnancies and idiopathic preterm labor between August 1988 and October 1989 were randomized by sealed envelopes to receive either indomethacin or intravenous magnesium sulfate.\n Of 101 eligible patients 49 were randomized to receive indomethacin. The two study groups were similar in regard to a number of entry variables, including gestational age, cervical examination, and contraction frequency. Indomethacin was as effective as magnesium sulfate in delaying delivery > 48 hours, 90% versus 85%, and together with oral terbutaline in extending the gestation, 22.9 versus 22.7 days. Tocolysis with magnesium sulfate was discontinued in eight (15%) patients because of maternal side effects, in contrast to none in the indomethacin group, p < 0.05.\n For gestations < 32 weeks indomethacin may be considered an appropriate alternative to magnesium sulfate as a first-time tocolytic agent.", "Magnesium sulfate has been recommended as a safe and effective agent for inhibiting preterm labor. Its reported adequacy as a tocolytic agent, however, has not been substantiated by randomized, controlled trials. To assess the efficacy of magnesium sulfate, we initiated a prospective, randomized study comparing the capabilities of magnesium sulfate, terbutaline and a placebo (5% dextrose in lactated Ringer's solution) for labor inhibition. The study population consisted of 54 patients between 26 and 34 weeks of gestation and in preterm labor. The diagnosis of labor was made if, following hydration, persistent uterine contractions occurred at a frequency of at least three in a ten-minute period and cervical examination suggested active labor. Success was defined as postponement of delivery for at least 48 hours after initiation of therapy. Despite a trend toward increased efficacy in the terbutaline group there were no significant differences between the three treatment groups with regard to capability of delaying delivery at least 48 hours. Also, there were no significant differences between the groups with regard to gestational age at delivery, birth weight and neonatal survival. The fact that delivery occurred in less than 48 hours of approximately one-half the patients under the best of circumstances emphasizes the need for more effective techniques for the inhibition of preterm labor and the need for a better understanding of the mechanisms involved in the initiation of preterm labor.", "The purpose of the study was to observe and compare the effects of ritodrine hydrochloride and magnesium sulfate on maternal fluid dynamics.\n Fourteen women in preterm labor were prospectively studied during tocolytic therapy with either ritodrine hydrochloride or magnesium sulfate. The cardiovascular and renal effects of a pretreatment crystalloid infusion were compared with those observed during tocolytic therapy. Profile analysis and repeated measures of variance were used to analyze the data.\n Ritodrine hydrochloride was associated with decreased colloid osmotic pressure, hematocrit, and serum proteins and increased maternal and fetal heart rates. Arginine vasopressin levels increased during the first 2 hours of therapy, then returned to baseline. Sodium excretion was reduced and there was marked fluid retention. Intravenous magnesium sulfate also resulted in a reduction of colloid osmotic pressure, but hematocrit, serum protein concentration, arginine vasopressin, maternal and fetal heart rates, and mean arterial pressure were minimally affected. Sodium excretion increased to a maximum at 6 to 8 hours of treatment, then returned to baseline. A positive fluid balance was also noted in magnesium sulfate-treated patients but to a lesser degree than with ritodrine.\n Sodium retention appears to be the primary cause of plasma volume expansion in ritodrine-treated patients, whereas volume expansion during magnesium sulfate therapy is probably related to intravenous overhydration. In the absence of risk factors for pulmonary capillary membrane injury, available evidence supports volume overload as the principal mechanism for pulmonary edema during tocolytic therapy.", "One hundred fifty-six women with preterm labor between 24 and 34 weeks' gestation were randomized to receive either intravenous magnesium sulfate or no tocolytic therapy. Magnesuim sulfate infusions of up to 3 gm/hr were used in 76 pregnancies and resulted in a mean serum magnesium concentration of 5.5 +/- 1.4 mEq/L (mean +/- SEM). Compared with 80 control pregnancies, magnesium sulfate tocolysis had no significant effect on duration of gestation, birth weight, neonatal morbidity, and perinatal mortality. We conclude that clinically safe infusions of magnesium sulfate are ineffective when used to prevent preterm birth.", "The efficacy of magnesium sulfate was analyzed in relation to ritodrine hydrochloride. Patients presenting in preterm labor between 20 and 35 weeks' gestation were prospectively randomized. Tocolysis was achieved for more than 72 hours in 35 of 40 cases (88%) where magnesium sulfate was administered and 31 of 39 cases (79%) in which ritodrine hydrochloride was infused. Delay of greater than or equal to 7 days was achieved in 75% and 72% of cases, respectively. The mean dosage to achieve tocolysis was 4.5 gm/hr, in the magnesium sulfate group and 210.0 micrograms/hr in ritodrine hydrochloride-treated patients. The mean magnesium level to achieve tocolysis was 6.60 mg/dl. Side effects in the two groups were similar in number but less alarming in the magnesium sulfate group. Magnesium sulfate was found to be easy to administer and clinically efficacious. Its tocolytic action was found to be dose dependent and drug concentrations are easily determined. On the basis of this work and data from other investigators, magnesium sulfate should be used as the first line of tocolytic therapy with ritodrine hydrochloride as its pharmacologic backup.", "Our purpose was to establish the efficacy and safety of nifedipine versus magnesium sulfate in arresting preterm labor and the efficacy of nifedipine versus terbutaline in preventing recurrent labor.\n Singleton pregnancies at < 34 weeks in preterm labor were randomized to either oral nifedipine or intravenous magnesium sulfate. In case of tocolysis failure ritodrine was added. After labor was arrested, the patients in the nifedipine group were maintained on oral nifedipine, and those in the magnesium sulfate group were treated with oral terbutaline until completing 34 weeks.\n Of 100 patients 80 were considered eligible, of whom 39 were randomized to the nifedipine group. Both groups were comparable in terms of a number of entry variables, including cervical examination, contraction frequency, and gestational age. Both drugs were equally effective in arresting labor and delaying delivery > 48 hours, 92% versus 93%. Both study groups had a similar incidence of side effects, although four (10%) of magnesium sulfate-treated patients required drug discontinuation because of severe symptoms. Nifedipine was as effective as terbutaline in preventing recurrent labor, 26% versus 24%, and in achieving a gestation > 34 weeks, 62% versus 68%.\n Oral nifedipine is as effective as magnesium sulfate and terbutaline in arresting and preventing idiopathic preterm labor.", "Magnesium sulfate has been recommended as a safe and effective tocolytic agent. However has not been substantiated by randomized, controlled trials. To assess the efficacy of magnesium sulfate, we initiated prospective randomized study competing the capabilities of magnesium sulfate and terbutaline for labor inhibition. The study population consisted of 30 patients (15 patients with terbutaline and 15 patients with magnesium sulfate) between 28 and 36 weeks of gestation and in preterm labor. One patient in terbutaline group was excluded of the study because we found a severe fetal distress. The diagnosis of labor was made if, persistent uterine contractions occurred at a frequency of at last three in a team-minute period and cervical examination suggested active labor. Success was defined as postponement of delivery for at least 48 hours after initiation of therapy. Despite a trend toward increased efficacy in the terbutaline group (tocolytic Bishop grade and its success) there were no significant differences between the two treatment groups with regard to capability of delaying delivery at least 48 hours. Although there were significant differences for terbutaline regard the tocolysis time. For all these reasons, the efficacy between both groups of treatment is similar, and in a future cases, will be necessary to choose the better agent for every case to study.", "The purpose of this study was to determine whether the use of antenatal magnesium sulfate prevents adverse outcomes (neonatal intraventricular hemorrhage, periventricular leucomalacia, death, and cerebral palsy).\n In a controlled trial, we randomized mothers in preterm labor to magnesium sulfate, \"other\" tocolytic, or placebo. At delivery, umbilical cord blood was collected for the later determination of serum ionized magnesium levels. Neonatal cranial ultrasound scans were obtained periodically for the diagnosis of intraventricular hemorrhage and periventricular leucomalacia. Among survivors, the diagnosis of cerebral palsy was made at age 18 months.\n Children with adverse outcomes had higher umbilical cord magnesium levels at delivery. In regression models that controlled for confounders, which included very low birth weight, magnesium remained a significant risk factor (adjusted odds ratio, 3.7; 95% CI, 1.1-11.9; P =.03).\n Contrary to original hypotheses, this randomized trial found that the use of antenatal magnesium sulfate was associated with worse, not better, perinatal outcome in a dose-response fashion.", "Ritodrine, terbutaline, and magnesium sulfate have all been used in the United States as tocolytic drugs. Studies have shown each of these drugs to be effective in suppressing preterm labor. The current study was undertaken in order to compare their relative safety and efficacy and to evaluate the effectiveness of a second drug when the first-used drug failed to stop contractions. No differences in efficacy could be demonstrated between the drugs; however, there was a marked difference in the incidence of maternal side effects. Because of an unacceptable level of side effects, we have stopped the use of terbutaline at our institution." ]

[ "20128938", "15815217", "8382424" ]

[ "Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study.", "Probiotics affects vaginal flora in pregnant women, suggesting the possibility of preventing preterm labor.", "Bacterial vaginosis in pregnancy treated with yoghurt." ]

[ "The perinatal nutritional environment impacts upon the health and well-being of mother and child also in the long term. The aim of the present study was to determine the safety and efficacy of perinatal probiotic-supplemented dietary counselling by evaluating pregnancy outcome and fetal and infant growth during the 24 months' follow-up. Altogether, 256 women were randomised at their first trimester of pregnancy into a control and a dietary intervention group. The intervention group received intensive dietary counselling provided by a nutritionist and were further randomised, double-blind to receive probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12; diet/probiotics) or placebo (diet/placebo). Firstly, probiotic intervention reduced the frequency of gestational diabetes mellitus (GDM); 13 % (diet/probiotics) v. 36 % (diet/placebo) and 34 % (control); P = 0.003. Secondly, the safety of this approach was attested by normal duration of pregnancies with no adverse events in mothers or children. No significant differences in prenatal or postnatal growth rates among the study groups were detected. Thirdly, distinctive effects of the two interventions were detected; probiotic intervention reduced the risk of GDM and dietary intervention diminished the risk of larger birth size in affected cases; P = 0.035 for birth weight and P = 0.028 for birth length. The results of the present study show that probiotic-supplemented perinatal dietary counselling could be a safe and cost-effective tool in addressing the metabolic epidemic. In view of the fact that birth size is a risk marker for later obesity, the present results are of significance for public health in demonstrating that this risk is modifiable.", "nan", "As various drugs might have an effect on the fetus during pregnancy, the use of drugs should be minimized in the pregnant woman. Since bacterial vaginosis (BV) can be associated with prematurity and postpartum complications, we searched for alternative therapy for its cure during pregnancy. Commercial yoghurt incorporates both factors necessary for maintaining the protective mechanism of the vagina, vaginal pH and lactobacillus. A total of 32 women with BV in the first trimester of pregnancy were treated with intravaginal application of yoghurt. The result was favorable indicating that the continuous correction of vaginal pH and lactobacillus flora is crucial for normal vaginal ecology. During pregnancy, a local treatment restoring the normal acidity and vaginal flora, without systemic effect, may be preferable to any other treatment." ]

[ "16860624", "2403655", "15570201", "21259031", "20538079", "15737849", "14505238", "16930145", "6243916", "4577070", "18453491", "11141221", "9327671", "1448739" ]

[ "Predictive risk score for infection after inguinal hernia repair.", "Perioperative antibiotic prophylaxis for herniorrhaphy and breast surgery.", "The role of antibiotic prophylaxis in prevention of wound infection after Lichtenstein open mesh repair of primary inguinal hernia: a multicenter double-blind randomized controlled trial.", "Prospective randomized evaluation of prophylactic antibiotic usage in patients undergoing tension free inguinal hernioplasty.", "Prophylactic antibiotics in open mesh repair of inguinal hernia - a randomized controlled trial.", "A randomized, double-blind, placebo-controlled trial to determine effectiveness of antibiotic prophylaxis for tension-free mesh herniorrhaphy.", "The role of antibiotic prophylaxis on wound infection after mesh hernia repair under local anesthesia on an ambulatory basis.", "The role of antibiotic prophylaxis in elective tension-free mesh inguinal hernia repair: results of a single-centre prospective randomised trial.", "Polyglycolic acid, silk, and topical ampicillin. Their use in hernia repair and cholecystectomy.", "The reduction of surgical wound infections by prophylactic parenteral cephaloridine. A controlled clinical trial.", "The role of antibiotic prophylaxis in mesh repair of primary inguinal hernias using prolene hernia system: a randomized prospective double-blind control trial.", "Effect of single-dose prophylactic ampicillin and sulbactam on wound infection after tension-free inguinal hernia repair with polypropylene mesh: the randomized, double-blind, prospective trial.", "Antibiotic prophylaxis and open groin hernia repair.", "Local antibiotic prophylaxis in inguinal hernia repair." ]

[ "Identification of subgroups of patients at high and low risk for global infectious complications (GIC) after inguinal hernia repair without mesh.\n A database of 1254 patients who underwent inguinal hernia repair without mesh, issued from 3 prospective multicenter randomized trials, has been established (group A). After multivariate analysis, a score for GIC was calculated and tested using data from a similar prospective randomized multicenter study (group B).\n A risk score for GIC was constructed: -4.7 + (0.95 x age > or =75 years) + (1.1 obesity) + (2.1 x urinary catheter). In case of score less than -4.2 (low-risk group), the GIC rate was 2.7%; therefore, in case of score more than -4.2 (high-risk score), the GIC rate was 14.3% (P < .001). In the low-risk group, the administration of antibiotic prophylaxis did not reduce the infectious complication rate, while in high-risk group the administration of antibiotic prophylaxis significantly reduced the rates of surgical site infection, GIC, and urinary infection by 72%, 67%, and 76.8%, respectively.\n This study demonstrates the efficacy of antibiotic prophylaxis in inguinal hernia surgery in the subgroup of high-risk patients.", "We assessed the efficacy of perioperative antibiotic prophylaxis for surgery in a randomized, double-blind trial of 1218 patients undergoing herniorrhaphy or surgery involving the breast, including excision of a breast mass, mastectomy, reduction mammoplasty, and axillary-node dissection. The prophylactic regimen was a single dose of cefonicid (1 g intravenously) administered approximately half an hour before surgery. The patients were followed up for four to six weeks after surgery. Blinding was maintained until the last patient completed the follow-up and all diagnoses of infection had been made. The patients who received prophylaxis had 48 percent fewer probable or definite infections than those who did not (Mantel-Haenszel risk ratio, 0.52; 95 percent confidence interval, 0.32 to 0.84; P = 0.01). For patients undergoing a procedure involving the breast, infection occurred in 6.6 percent of the cefonicid recipients (20 of 303) and 12.2 percent of the placebo recipients (37 of 303); for those undergoing herniorrhaphy, infection occurred in 2.3 percent of the cefonicid recipients (7 of 301) and 4.2 percent of the placebo recipients (13 of 311). There were comparable reductions in the numbers of definite wound infections (Mantel-Haenszel risk ratio, 0.49), wounds that drained pus (risk ratio, 0.43), Staphylococcus aureus wound isolates (risk ratio, 0.49), and urinary tract infections (risk ratio, 0.40). There were also comparable reductions in the need for postoperative antibiotic therapy, non-routine visits to a physician for problems involving wound healing, incision and drainage procedures, and readmission because of problems with wound healing. We conclude that perioperative antibiotic prophylaxis with cefonicid is useful for herniorrhaphy and certain types of breast surgery.", "To determine whether the use of prophylactic antibiotics is effective in the prevention of postoperative wound infection after Lichtenstein open mesh inguinal hernia repair.\n A recent Cochrane meta-analysis (2003) concluded that \"antibiotic prophylaxis for elective inguinal hernia repair cannot be firmly recommended or discarded.\"\n Patients with a primary inguinal hernia scheduled for Lichtenstein repair were randomized to a preoperative single dose of 1.5 g intravenous cephalosporin or a placebo. Patients with recurrent hernias, immunosuppressive diseases, or allergies for the given antibiotic were excluded. Infection was defined using the Centers for Disease Control and Prevention criteria.\n We included 1040 patients in the study between November 1998 and May 2003. According to the intention-to-treat principle, 1008 patients were analyzed. There were 8 infections (1.6%) in the antibiotic prophylaxis group and 9 (1.8%) in the placebo group (P = 0.82). There was 1 deep infection in the antibiotic prophylaxis group and 2 in the placebo group (P = 0.57). Statistical analysis showed an absolute risk reduction of 0.19% (95% confidence interval, -1.78%-1.40%) and a number needed to treat of 520 for the total number of infections. For deep infection, the absolute risk reduction is 0.20% (95% confidence interval, -0.87%-0.48%) with a number needed to treat of 508.\n A low percentage (1.7%) of wound infection after Lichtenstein open mesh inguinal (primary) hernia repair was found, and there was no difference between the antibiotic prophylaxis or placebo group. The results show that, in Lichtenstein inguinal primary hernia repair, antibiotic prophylaxis is not indicated in low-risk patients.", "Assessment of the usefulness of antibiotic prophylaxis in inguinal hernioplasty.\n This prospective randomized double blind study was conducted on 98 patients. Group A (50 patients) received a single dose of intravenous amoxicillin and clavulanic acid, and Group P (48 patients) received an equal volume of normal saline placebo by intravenous bolus 30 min before the induction of anesthesia. Hernioplasty was performed with polypropylene mesh. Skin was closed using skin staples that were removed after complete wound healing. The surgical site infection was diagnosed according to APIC, CDC criteria ( http://www.apic.org ).\n The mean operative time was 38.8  ± 10.8 min in group A versus 40.9 ± 11.1 min in group P (P  = 0.34). The mean hospitalization time was 1.3 ± 0.463 days in group A versus 1.25 ± 0.438 days in group P (P = 0.58). Four patients (2%) in group A and 6 patients (2.88%) in group P had wound infections (P = 0.47). Group A had 3 superficial infections and 1 deep infection while group P had 5 superficial infections and 1 deep infection. Antibiotic treatment of the wound infection was successful in all patients. Wound culture showed Staphylococcus aureus infection in 1 patient each group, Streptococcus pyogenes in 1 group A patient and Pseudomonas aeruginosa in 1 group P patient. Cultures in other patients in both groups were reported to be sterile.\n Prophylactic antibiotic usage in patients undergoing tension free inguinal hernioplasty did not show any statistically significant beneficial effects in reduction of surgical site infection.", "The role of prophylactic antibiotics in mesh repair of inguinal hernia is unclear. A Cochrane meta-analysis in 2005 concluded that \"antibiotic prophylaxis for elective inguinal hernia repair cannot be firmly recommended or discarded\" and \"further studies are needed, particularly on the use for mesh repair.\" So, we designed a study to define the role of prophylactic antibiotics in mesh repair of inguinal hernia. We conducted a prospective, randomized, double-blind, trial comparing wound infection rates in 450 patients (225 received intravenous Cefazolin, 225 received a placebo) undergoing primary inguinal hernia repair electively using polypropylene mesh. 334 patients who completed a followup period of one month were analyzed. Age, American Society of Anesthesiologists class, type of hernia, type of anesthesia, grade of surgeon, pre and postoperative hospital stay and duration of operation were recorded. CDC criteria was used to define wound infection. Groups were well matched for all preoperative variables studied. The overall infection rate was 8.7% (29 out of 334). The incidence of wound infection in antibiotic group was 7% and 10.5% in control group. One from each group developed deep surgical site infection. Most of the infections occurred between the 7th and 12th post-operative day after discharge from the hospital. Antibiotic prophylaxis was associated with decreased incidence of wound infection when compared to control group, but the difference was not statistically significant. Based on our results we do not recommend the routine use of antibiotic prophylaxis in elective mesh repair of inguinal hernias.\n Copyright © 2010 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.", "In recent years, use of prosthetic material for inguinal hernia repair has increased dramatically. Tension-free repairs have gained popularity not only for recurrent or complicated hernias, but for primary hernia repairs as well. Although routine use of prophylactic antibiotics is not recommended in the Philippines for open nonimplant herniorrhaphy, there is little direct clinical evidence on which to base recommendations when implantable mesh is used.\n We conducted a prospective, randomized, double-blind, placebo-controlled trial comparing wound infection rates in 360 patients (180 received prophylactic antibiotics, 180 received a placebo) undergoing primary inguinal hernia repair electively using polypropylene mesh. Age, gender, American Society of Anesthesiologists class, type of hernia, type of anesthesia, and duration of operation were recorded. Infections were evaluated 1 week, 2 weeks, and 1 month after operation by an independent surgeon. All complications were recorded. Results were assessed using chi-square, Fisher's exact test, and Student's t-tests as appropriate.\n Groups were well matched for all preoperative variables studied, including comorbid conditions. Six patients from the antibiotic group and four from the placebo group failed to followup after the second week. Superficial surgical site infection developed in 3 patients (1.7%) from the antibiotic group and 6 (3.3%) from the placebo group (p = 0.50). One from each group developed deep surgical site infection. Both patients were readmitted and underwent repeated debridement, which eventually resulted in graft loss.\n Preoperative administration of single-dose antibiotic for tension-free inguinal mesh herniorrhaphy did not markedly decrease risk of wound infection in this patient population. Our results do not support use of antibiotic prophylaxis for tension-free mesh herniorrhaphy.", "Mesh prosthesis, local anesthesia, and ambulatory care have been widely introduced in recent decades in the treatment of inguinal hernia. The use of antibiotic prophylaxis during open inguinal hernia repair has been controversial. No prospective trial has been conducted to assess the role of antibiotic prophylaxis in patients operated on for inguinal hernia under the above-mentioned conditions. A prospective, randomized, double-blinded trial was initiated to assess the efficacy of antibiotic prophylaxis in the prevention of wound infection during open mesh inguinal hernia repair under local anesthesia on an ambulatory basis. Ninety-nine consecutive hernia repairs were randomized to receive 1 g of parenteral Cefazolin preoperatively or a placebo. No wound infections existed in the therapeutic group (0/50). Four infections appeared in the control group (4/49), and the study was suspended for ethical reasons when differences reached values close to statistical significance ( P=0.059). We conclude that a single dose of intravenous Cefazolin decreases the risk of wound infection during open mesh inguinal hernia repair under local anesthesia on an ambulatory basis.", "Hernia repair is one of the so-called clean operations. Many surgeons, however, use antibiotics, especially in the mesh repair era, without strong evidence to support this policy. We conducted a single-centre prospective randomised trial with a view to clarify this issue on a scientific basis. From January 2000 all patients undergoing elective inguinal hernia repair using a tension-free polypropylene mesh technique, provided they fulfilled predetermined criteria, were randomised to have a single dose of amoxicillin and clavoulanic acid or placebo in a double-blind manner. The main end point was to detect any difference in infectious complication rates - with specific interest to wound infection rates - between the two groups. Between January 2000 and June 2004, 386 patients entered the study (364 men and 22 women, median age 63 years, range 15-90 years) and were randomised to have antibiotic prophylaxis (group A, n = 193) or placebo (group B, n = 193). The two groups were comparable regarding demographic data. In total, 19 (5%) cases with infectious complications were detected. Fourteen of these were wound infections (3.7%). There were five cases of wound infection in group A and nine in group B (p = 0.4, Fisher's exact test). All wound infections were treated with antibiotics. The wound was opened in some cases. Mesh removal was not required in any of the cases. From the results of this study it does not appear that antibiotic prophylaxis offers any benefits in the elective mesh inguinal hernia repair.", "The effect of topical ampicillin sodium and polyglycolic acid and silk sutures on the recurrence of an existing hernia or an incisional hernia and on infection rates in clean abdominal wounds (herniotomies and simple cholecystectomies) was studied in a triple-blind, randomized trial with 398 consecutive patients. One infection, three suture sinuses, and two incisional hernias occurred among 113 patients with cholecystectomies, while the corresponding rates in 285 patients with hernia repairs were 11 infections, no suture sinuses, and three recurrent hernias. No effect of ampicillin could be demonstrated, nor was any difference between polyglycolic acid and silk sutures shown. No interaction between the antibiotic and suture material was found, and no side effects were observed. Wound infection was significantly more frequent in patients with postoperative seromas or hematomas.", "nan", "Antibiotic prophylaxis is being commonly used in mesh repair of inguinal hernia but its role has been questioned in a recent Cochrane analysis performed in 2003. Routine use of antibiotic prophylaxis in mesh repair of inguinal hernia can lead to bacterial resistance and increase in cost. In a present double-blind placebo controlled trial involving 120 patients undergoing inguinal hernia repair using prolene hernia system, we did not find any benefit of the routine use of antibiotic prophylaxis in terms of wound infection rate.", "To assess the value of single-dose, intravenous, prophylactic ampicillin and sulbactam (AS) in the prevention of wound infections during open prosthetic inguinal hernia repair by a double-blind, prospective, randomized trial.\n The use of antibiotic prophylaxis during open prosthetic inguinal hernia surgery is controversial, and no prospective trial has been conducted to examine this issue.\n Patients undergoing unilateral, primary inguinal hernia repair electively with the Lichtenstein technique using polypropylene mesh were randomized to receive 1.5 g intravenous AS before the incision or an equal volume of placebo according to a predetermined code of which the surgeons were unaware. Patients with recurrent, femoral, bilateral, giant, or incarcerated hernias or any systemic diseases were excluded. Age, sex, body mass index, American Society of Anesthesiologists score, type of hernia, type of anesthesia, duration of surgery, and use of drains were recorded. Infection was defined according to the criteria of Centers for Disease Control. Patients were evaluated 1 week, 1 month, 6 months, and 1 year after surgery by an independent surgeon. All complications were recorded. Results were assessed using chi-square, Fisher's exact, and Student t tests as appropriate.\n Between September 1996 and July 1998, 280 patients (140 AS, 140 placebo group) entered the protocol. Four patients from the AS group and seven from the placebo group were excluded because of inadvertent antibiotic administration or follow-up problems. Groups were well matched for all the variables studied and postoperative complications, excluding wound infections, which occurred at a rate of 0.7% in the AS group and 9% in the placebo group (P =.00153). Twelve patients in the placebo group developed wound infections, requiring five repeat hospital admissions in three patients. These three patients suffered deep infections reaching the graft, which resulted in graft loss in two. The single infected patient in the AS group had his graft removed as well because of deep persistent infection.\n This study documented a significant (10-fold) decrease in overall wound infections when single-dose, intravenous AS was used during Lichtenstein hernia repair. Deep infections and wound infection-related readmissions were also reduced by the use of AS. Proponents of mesh repairs may therefore be advised to use prophylactic single-dose intravenous antibiotic coverage in the light of the results of this trial. AS proved to be an effective antimicrobial agent.", "Antibiotic prophylaxis is not routinely given for nonimplant, clean operations, although this view has recently been challenged. We have conducted a randomized multicenter, double-blind prospective trial to compare co-amoxiclav with placebo in 619 patients undergoing open groin hernia repair. Altogether 563 (91%) patients fulfilled the protocol; 283 received co-amoxiclav and 280 placebo. There was no difference between the groups in the number of patients receiving local or general anesthetic, the type of repair performed, the use of a subcutaneous fat suture, the type of skin closure used, the use of wound analgesia, or the use of a wound drain. Patients were given a card to return to the hospital in the event of their wound discharging or their needing to see their general practitioner. All patients were reviewed at approximately 6 weeks after operation. Fifty (8.9%) patients sustained a wound infection, 25 in the co-amoxiclav group and 25 in the placebo group. We conclude that antibiotic prophylaxis is of no benefit to patients undergoing open groin hernia repair.", "We compared the effects of single dose (750 milligrams) prophylactic cefamandole delivered directly into the operative wound with local anesthesia (n = 162) with a control group (no antibiotics) (n = 162) in a randomized trial. No adverse effects were observed. There were seven wound abscesses in the untreated group compared with none in the group receiving antibiotic prophylaxis (p = 0.007). Six of the seven abscesses occurred as late as one month after the patient was discharged from the hospital. The costs of antibiotics used were ten times less than the costs of treatment of wound complications in the control group." ]

[ "387068", "327814", "6957127", "2223677", "801412", "5334978" ]

[ "Double blind trial of ritodrine and placebo in twin pregnancy.", "Effect of prophylactic outpatient administration of fenoterol on the time of onset of spontaneous labor and fetal growth rate in twin pregnancy.", "Prevention of prematurity in twin pregnancy by orally administered terbutaline.", "Failure to prevent preterm labour and delivery in twin pregnancy using prophylactic oral salbutamol.", "Ritodrine HCL for the prevention of premature labor in twin pregnancies.", "A double-blind trial of oral isoxuprine in the prevention of premature labour." ]

[ "In a double blind trial, 25 patients with twin pregnancy were given 40 mg of ritodrine hydrochloride by mouth daily and 24 similar patients received a placebo. The ritodrine group had no significant prolongation of pregnancy nor increase in birth weight, and a high incidence of side effects occurred.", "A double-blind trial was conducted on outpatients with twin gestations to assess the effect of prophylactic administration of fenoterol on the fetal growth rate and the timing of the spontaneous onset of labor. No significant differences could be shown between the fenoterol-treated group of patients and the control group given a placebo. It is concluded that prophylactic administration of fenoterol does not have a significant effect upon the incidence of preterm labor or growth retardation in twin pregnancy.", "The intention of this study was to evaluate whether perorally administrated terbutaline given prophylactically could reduce prematurity in twin pregnancy. In a double-blind study, 50 women with twin pregnancies were given either placebo (25) or terbutaline (25). Six in the terbutaline group and 15 in the placebo group went into preterm labor which required intravenous infusion of terbutaline. The difference is statistically significant (p = 0.010). The total number of days in hospital due to preterm labor was 115 in the terbutaline group and 256 in the placebo group. There is a slight difference in prematurity (delivery week less than 37th week) - the placebo group gave birth somewhat earlier - but this difference is not statistically significant. When evaluating this, it has to be considered that 15 of the 25 in the placebo group received parenteral treatment with terbutaline because of preterm labor. Birth weights of the twins in relation to gestational age seemed to be the same in the two groups.", "A double blind, controlled study was performed to see whether the use of prophylactic oral salbutamol would reduce the incidence of preterm labour in twin pregnancy. Of the 144 women studied, 74 took salbutamol and 70 placebo. No difference was found in the length of gestation, birthweight or fetal outcome, although fewer babies suffered from respiratory distress syndrome in the salbutamol group. Women did not experience troublesome side-effects from salbutamol.", "The perinatal mortality rate for twin gestation is in the range of 15%, and this is due predominantly to prematurity, although twins may also be born growth retarded. Ritodrine HCl, a beta sympathomimetic drug, has been shown to be effective, both in stopping premature labor and in preventing intrauterine growth retardation. With this in mind, a double-blind study using ritodrine HCl or placebo was begun in order to study its effect on premature labor, intrauterine growth retardation, and the perinatal mortality rate in twins. Thus far, 30 patients have delivered and have been followed to 6 weeks postpartum. Although the results on individual patients have remained blinded to the investigators, an initial evaluation of the ritodrine and placebo groups have revealed no difference with respect to gestational age, birth weight, or perinatal mortality. These preliminary results are not significant. However, it appears that ritodrine HCl is a safe oral agent for the antepartum gravida and her fetus. The study will be continued until approximately 100 patients have been enrolled.", "nan" ]

[ "8775240", "2067772", "9737127", "16637377", "3357663", "3300348", "18803892" ]

[ "The effect of intraumbilical oxytocin on the third stage of labour.", "A randomized comparison of umbilical vein and intravenous oxytocin during the puerperium.", "Effect of umbilical vein oxytocin injection on the third stage of labor: a randomized controlled study.", "[Oxitocin trough umbilical vein to shorten the third stage of labor].", "The effect of intraumbilical oxytocin on the third stage of labor.", "Influence of umbilical vein administration of oxytocin on the third stage of labor: a randomized, double-blind, placebo-controlled study.", "Intraumbilical veinous injection oxytocin in the active management of third stage of labour." ]

[ "The umbilical vein administration of oxytocin in saline was compared with umbilical vein saline alone and the traditional management of the third stage of labour. Seventy-two women were randomized to 3 groups. Group 1 received intraumbilical 20 IU of oxytocin diluted to 40 mL with saline. Group 2 received intraumbilical vein 40 mL of saline while subjects in group 3 were managed according to the standard protocol without any intraumbilical injection. No significant differences were found in terms of the length of the third stage, the blood loss in the third stage and postpartum haematocrit differences among the 3 groups. The administration of diluted oxytocin or saline do not seem to have any superiority to the traditional management of the third stage of labour.", "Oxytocin was administered in a randomized fashion via either the umbilical or maternal intravenous route. Women who received intraumbilical oxytocin had significantly greater calculated blood loss compared with those who received peripheral administration (P = .01). This greater blood loss was confirmed by a decrease in hematocrit and hemoglobin concentrations after delivery. There was no difference between the groups in the length of the third stage of labor. The incidence of fetomaternal transfusion was higher in the intraumbilical group (P = .07). We conclude that intraumbilical oxytocin is no more beneficial than peripheral administration.", "To evaluate the effect of umbilical vein oxytocin injection on the duration of third stage of labor, and estimated blood loss within 24 hours postpartum, in 50 vaginal parturients at Rajavithi Hospital from March 1, 1994 and June 30, 1995. The parturients were randomized to administered either an umbilical vein injection of 20 units of oxytocin diluted to 20 ml with normal saline (oxytocin group) or only normal saline 20 ml (control group) immediately after cord clamping. There were 25 paturients in each group. The duration of the third stage of labor in the oxytocin group was significantly shorter than that in the control group. In only 1 case of the control group was manual placental removal performed. The estimated blood loss within 24 hours postpartum in both groups was not statistically different. Twenty units of umbilical vein oxytocin injection was effective to shorten the duration of the third stage of labor but were not effective to reduce the estimated blood loss within 24 hours postpartum. The need for a further large scale study in the future was suggested.", "To examine the efficacy and safety of oxitocin administered through umbilical vein after delivery to diminish the incidence of retained placenta, blood loss and third stage of labour.\n A double blind, clinical trial was performed in which 64 women in labour, any age, with normal pregnancies, with gestational time between 37 to 42 weeks, were randomized to one of two groups. Group 1 received 10 UI of oxitocin (2 mL) diluted in 18 mL of saline solution through umbilical vein, immediately after delivery. Group 2 received only 20 mL of saline solution. Blood loss, time of third stage of labour, retained placenta, nausea, vomit and arterial hypotension were measured.\n Blood loss was 263.7 +/- 220.9 mL in group 1 (n=32) and 286.7 + 230.4 in group 2 (n=32) (p=0.68, Student T test). Time of third stage of labour was 265.3 +/- 383.9 seconds in group 1 and 197.1 +/- 314.3 in group 2 (p=0.44, Student T test). There was one retained placenta in group 1 and two in group 2 (RR 0.5 IC 0.04 a 5.24). There were not side effects in any group.\n Oxitocin trough umbilical vein immediately after delivery was not useful to diminish blood loss, retained placenta or time of third stage of labour.", "To determine whether intraumbilical oxytocin would shorten the third stage of labor, we enrolled 50 normal parturients into a randomized, double-blind protocol. Either 10 U of oxytocin diluted to 20 mL in normal saline (25 subjects) or 20 mL of normal saline alone (25 subjects) was injected into the placental circulation within one minute after cord clamping. The mean (+/- SD) duration of the third stage was 4.1 +/- 2.0 minutes in saline-treated subjects and 4.6 +/- 3.4 minutes in those treated with oxytocin. Intraumbilical oxytocin was not effective in shortening the normal third stage of labor.", "A randomized, double-blind, placebo-controlled study evaluated the influence of umbilical vein administration of oxytocin on the third stage of labor. Five minutes after delivery, 37 women received 10 units of oxytocin diluted in physiologic saline solution to a total volume of 20 ml; 41 women received 20 ml of saline solution alone. There was no significant difference between groups in mean (+/- SD) injection-placental expulsion interval (9 +/- 7 versus 10 +/- 8 minutes).", "To determine the role of intraumbilical vein oxytocin reducing blood loss during and after one hour of delivery of placenta and its efficacy in reducing the frequency of retained placenta.\n Randomized controlled trial.\n Combined Military Hospital, Multan, from June 2002 to October 2002.\n Five hundred parturient women with low risk singleton term pregnancy were enrolled in the study. Two hundred and fifty women each were included in the study and control group after randomization. The patients and health care providers both were blinded to the intervention. Primary outcome measures were kept as duration and amount of blood loss in third stage of labour. Secondary outcome measures included incidence of retained placenta, abdominal need for additional utero-tonics, frequency of postpartum pain, nausea and vomiting, fever, need for blood transfusion, establishment of breast feeding and total duration of hospital stay.\n Women in study group who received intraumbilical vein syntocinon lost 234.03 ml of blood while the control group lost 276.51 ml (p=0.001). Mean duration of third stage was 2.59 minutes in the study group and 7.67 minutes in the control group (p<0.001). The frequency of retained placenta was 1.2%, which involved only the control group. Abdominal pain was experienced by study group but the difference was not found statistically significant. Nausea and vomiting was more in study group (p=0.001). No discernible difference was found in length of hospital stay, the need for blood transfusion, fever and establishment of breast-feeding in both groups.\n The addition of intraumbilical vein syntocinon 10 units resulted in marked reduction in amount of blood loss, duration of third stage and incidence of retained placenta in comparison to intravenous 5 IU oxytocin+0.5 mg ergometrine alone." ]

[ "8420315", "11430967", "7650662", "8684757", "1867580" ]

[ "The PROEF diet--a new postoperative regimen for oral early feeding.", "Early feeding after cesarean: randomized trial.", "Safety and efficacy of early postoperative solid food consumption after cesarean section.", "Postoperative management of cesarean patients: the effect of immediate feeding on the incidence of ileus.", "Immediate postoperative oral hydration after caesarean section." ]

[ "The purpose of this study was to determine if immediate postoperative feeding of a new oral elemental diet (PROEF diet) would be tolerated by patients and to determine its effect on gastrointestinal function after cesarean section.\n One hundred eighteen patients undergoing cesarean section were randomly assigned by a computer-generated list of numbers to receive either the PROEF diet (60 patients) or routine postoperative dietary management (58 patients). Gastrointestinal morbidity was analyzed by an independent-samples t test.\n The PROEF diet group has a more rapid return of normal bowel sounds, 10.3 versus 14.5 hours (p = 0.001), and earlier acceptance of a regular diet, 2.0 versus 2.3 days (p = 0.008).\n The PROEF diet was well tolerated in cesarean section patients with no increase in gastrointestinal morbidity when compared with a control group of patients. This dispels the classic teaching that postoperative patients may not have oral intake until the return of normal bowel function. Further study is necessary to support the theoretic benefits that may accrue from early feeding of an elemental diet.", "To study the rate of ileus symptoms and hospital course of women who are offered solid food shortly after cesarean delivery.\n This study involved women delivered by cesarean under regional anesthesia. Exclusion criteria included general anesthesia, magnesium sulfate, intra-operative bowel injury or bowel surgery, or other conditions that precluded early feeding. Early-fed women were offered regular diets within 8 hours of surgery, and controls were given nothing by mouth for 12-24 hours, advanced to clear liquids on the first postoperative day, and then given solid food on the second or third postoperative day.\n Sixty women were assigned randomly to each method. Early-fed women received solid food sooner after surgery, 5.0 +/- 1.2 hours versus 40.0 +/- 10.6 hours. The incidences of mild ileus symptoms and postoperative complications were similar in both groups; however, the study did not have an adequate sample size to definitively assess safety concerns. Women in the early-fed group had shorter hospital stays (49.5 +/- 12.7 hours versus 75.0 +/- 12.3 hours, P <.001), and shorter time intervals from surgery to bowel movement, 34.5 hours (interquartile range 25.3-48.8) versus 51.0 (43.3-62.0) hours, P <.001. In the early-fed group, women whose operative times exceeded 40 minutes were more likely to have symptoms of mild ileus.\n Early initiation of solid food after cesarean delivery appears to be well tolerated and may be associated with a shorter hospital stay. Early-fed women whose operations exceed 40 minutes may be more likely to have mild ileus symptoms.", "Traditionally patients have received a physician-dictated regimen of gradual expansion of their diets following cesarean section. This has been based upon concern about the possibility of ileus from expanding the diet too rapidly. Given the economic necessity of earlier postoperative discharge following abdominal delivery, many patients have solid food reintroduced in their diets around the time they leave the hospital. This prospective, randomized, controlled study compared a traditional, gradual dietary expansion scheme with patient-determined reintroduction of solid food, which was offered within eight hours of surgery. The hypotheses were that women would eat more rapidly after cesarean section when given the opportunity and that early solid food consumption would reduce the need for analgesia. The results indicated that both hypotheses were correct. Given the opportunity, women will eat solid food very soon after cesarean section (mean +/- SD 10.2 +/- 5.2 hours from surgery to onset of solid food consumption) as compared to women on a traditional dietary expansion regimen (mean +/- SD 41.5 +/- 16.0 hours, P < .001). Women offered food within hours of cesarean section required less patient-requested injectable narcotic postoperatively than did women on gradual dietary expansion (median, 75 mg versus 225 mg meperidine, P < .05). There was no evidence of compromise of safety or comfort from introducing solid food early and allowing the patient to decide when to eat postoperatively. The conclusion from these data is that early postoperative feeding after cesarean section is a safe and effective alternative for most women, who now face early hospital discharge.", "To evaluate the effect of immediate feeding on gastrointestinal function in patients undergoing cesarean delivery.\n A prospective study was conducted in which patients were randomized to one of two groups, either early feeding or delayed feeding, ie, feeding according to the institution's current protocol. Questionnaires were filled out by the subjects on the day of discharge. Fisher exact test was used to compare the two groups with respect to the type of anesthetic used and to compare the incidence of gastrointestinal symptoms. A one-sided exact binomial confidence interval was used to determine the upper bound of the likelihood of paralytic ileus. Logistic regression analysis was used to evaluate the presence of ileus symptoms when controlling for the type of anesthetic used.\n There were no significant differences between the control and study groups. There was no significant difference in the number of gastrointestinal symptoms between the two groups. The incidence of postoperative paralytic ileus was zero in both the study and control groups.\n Routine early feeding of subjects undergoing cesarean delivery can be implemented without an increase in gastrointestinal symptoms or paralytic ileus.", "A study was carried out to assess the effects of immediate postoperative oral rehydration in 51 unpremedicated women undergoing caesarean section under epidural anesthesia. The patients were randomly assigned to 2 groups: group 1 (n = 22)--fasting at least until 24 hours after the end of the operation, and group 2 (n = 29)--receiving immediate oral intake of fluids (water, tea or coffee with sugar) without limitation of quantity. The 2 groups were compared for the occurrence of postoperative nausea and vomiting, onset of peristalsis, rectal gas emission, first bowel movement, and possible complications. The results demonstrate no significant differences between the parturients who drank immediately postoperatively as compared to those in whom oral fluid intake was delayed for 24 hours or more. It is concluded that immediate postoperative oral rehydration had no harmful effect upon peristalsis post-caesarean section." ]

[ "16318613", "20677024", "19566557" ]

[ "Routine cervical dilatation during elective cesarean section and its influence on maternal morbidity: a randomized controlled study.", "A randomized controlled study investigating the necessity of routine cervical dilatation during elective cesarean section.", "Is routine cervical dilatation necessary during elective caesarean section? A randomised controlled trial." ]

[ "To determine the effect of routine intraoperative cervical dilatation during elective cesarean section on maternal morbidity.\n Patients with even numbers in the operative elective cesarean section list were included in the study. Of these, every second patient underwent intraoperative cervical dilatation. All participants in the two groups had otherwise similar preoperative care, operative procedures and subsequent clinical care. Blood loss was estimated and maternal infection status was assessed postoperatively by any rise of temperature or wound infection.\n Of the 131 patients included in the study, 67 underwent cervical dilation and 64 served as controls. There was no significant difference in postoperative hemoglobin, incidence of fever, or wound infection between the two groups. Only two of the cervical dilation group and one control patient developed postoperative fever. A hemoglobin drop of more than 0.5 g/dL was noted in 27 and 26 patients in the cervical dilation and the no dilation groups, respectively (NS). None of the study patients had signs of wound infection.\n Intraoperative cervical dilatation during elective cesarean section did not reduce the risk of postoperative maternal fever, wound infection or change in hemoglobin concentration.", "To investigate if it was necessary to dilate the cervix routinely during elective cesarean section and to determine the effects of this traditional maneuver on maternal morbidity.\n A total of 150 patients meeting eligibility criteria were enrolled in this prospective, randomized controlled study. Patients were allocated randomly into cervical dilatation group or non-dilated group. In the cervical dilatation group, the surgeon performed cervical dilatation by inserting a double-gloved index finger into the cervical canal of the patients after extraction of placenta and membranes. Endometrial cavity thickness of the patients at postoperative 24 h, development of postoperative febrile-infectious morbidity and postoperative hemoglobin levels were evaluated and compared between the groups.\n The two groups were comparable with regard to demographic and clinical properties. Mean postoperative endometrial cavity thickness of the dilated group was significantly less than the non-dilated group (6.87 ± 2.50, 9.51 ± 3.35 respectively, p < 0.0001). The level of hemoglobin reduction was comparable between the groups (p = 0.37). Febrile morbidity was seen in one patient in the dilated group. Endometritis or wound infection was not encountered in either group during the puerperium.\n Cervical dilatation seems to be an unnecessary intervention during the cesarean section.", "The purpose of this prospective randomised study was to determine the effect of routine cervical dilatation during elective caesarean section on maternal morbidity.\n Participants with indication for elective caesarean section were randomly allocated to two groups. Group A (n = 200) women with intraoperative cervical dilatation; group B (n = 200) women with no intraoperative cervical dilatation.\n No demographic differences were observed between groups. There was no significant difference between groups in infectious morbidity (P = 0.87) (relative risk (RR) 1.11, 95% confidence interval (CI) 0.58-2.11), endometritis (P = 0.72) (RR 1.68, 95% CI 0.39-7.14), febrile morbidity (P = 0.66) (RR 1.21, 95% CI 0.51-2.87), wound infection (P = 0.82) (RR 1.11, 95% CI 0.44-2.81), endometritis (P = 0.72) (RR 1.68, 95% CI 0.39-7.14) or urinary tract infection (P = 1.00) (RR 1.00, 95% CI 0.28-3.50), and estimated blood loss (P = 0.2). However, group A had longer operative times compared with the group B (P = 0.01).\n Intraoperative digital cervical dilatation during elective caesarean section did not reduce blood loss and postoperative infectious morbidity. The routine digital cervical dilatation during elective caesarean section is not recommended." ]

[ "12126818", "8632574", "15036669", "15337535", "11111188", "15084760", "3133327", "11483335", "15817329", "16257791", "14767287", "10096378", "10588962", "12101195", "11458055", "16145740", "9123738", "13129633", "8791047", "12913699", "11743286" ]

[ "Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial.", "Randomized study of neoadjuvant testicular androgen ablation therapy before radical prostatectomy in men with clinically localized prostate cancer.", "Prospective randomized trial comparing flutamide as adjuvant treatment versus observation after radical prostatectomy for locally advanced, lymph node-negative prostate cancer.", "Report of a multicenter Canadian phase III randomized trial of 3 months vs. 8 months neoadjuvant androgen deprivation before standard-dose radiotherapy for clinically localized prostate cancer.", "4-Year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. European Study Group on Neoadjuvant Treatment of Prostate Cancer.", "Neoadjuvant hormone treatment with leuprolide acetate depot 3.75 mg and cyproterone acetate, before radical prostatectomy: a randomized study.", "Adjuvant estrogen following radiation therapy for stage C adenocarcinoma of the prostate: long-term results of a prospective randomized study.", "Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate.", "Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31.", "Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial.", "The efficacy and sequencing of a short course of androgen suppression on freedom from biochemical failure when administered with radiation therapy for T2-T3 prostate cancer.", "Prolonged neoadjuvant combined androgen blockade leads to a further reduction of prostatic tumor volume: three versus six months of endocrine therapy.", "Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer.", "Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.", "Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects.", "Bicalutamide ('Casodex') 150 mg as adjuvant to radiotherapy in patients with localised or locally advanced prostate cancer: results from the randomised Early Prostate Cancer Programme.", "Neoadjuvant hormonal therapy: the Canadian experience.", "Acceptability of short term neo-adjuvant androgen deprivation in patients with locally advanced prostate cancer.", "The risk of malignancy in the surgical margin at radical prostatectomy reduced almost three-fold in patients given neo-adjuvant hormone treatment.", "Long-term followup of a randomized trial of 0 versus 3 months of neoadjuvant androgen ablation before radical prostatectomy.", "Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxMo prostate cancer: 5-year results." ]

[ "We did a randomised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone (LHRH) to investigate the added value of long-term androgen suppression in locally advanced prostate cancer.\n Between 1987 and 1995, 415 patients were randomly assigned radiotherapy alone or radiotherapy plus immediate androgen suppression. Eligible patients had T1-2 tumours of WHO grade 3 or T3-4 N0-1 M0 tumours; the median age of participants was 71 years (range 51-80). In both treatment groups, 50 Gy radiation was delivered to the pelvis over 5 weeks, and 20 Gy over 2 weeks as a prostatic boost. Goserelin (3.6 mg subcutaneously every 4 weeks) was started on the first day of irradiation and continued for 3 years; cyproterone acetate (150 mg orally) was given for 1 month starting 1 week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analyses were by intention to treat.\n 412 patients had evaluable data, with median follow-up of 66 months (range 1-126). 5-year clinical disease-free survival was 40% (95% CI 32-48) in the radiotherapy-alone group and 74% (67-81) in the combined-treatment group (p=0.0001). 5-year overall survival was 62% (52-72) and 78% (72-84), respectively (p=0.0002) and 5-year specific survival 79% (72-86) and 94% (90-98).\n Immediate androgen suppression with an LHRH analogue given during and for 3 years after external irradiation improves disease-free and overall survival of patients with locally advanced prostate cancer.", "We determined whether 12 weeks of neoadjuvant testicular androgen ablation therapy using a luteinizing hormone-releasing hormone agonist could improve pathological outcomes in men undergoing radical retropubic prostatectomy for clinically localized (stages T1C, T2A and T2B) prostatic carcinoma.\n A total of 56 participants was randomized to receive either monthly injections of a luteinizing hormone-releasing hormone agonist at 4-week intervals followed by radical retropubic prostatectomy (28) or to undergo immediate radical retropubic prostatectomy alone (28). Operations were performed via similar technique and all prostatic specimens were processed histologically in their entirety.\n There was no improvement in pathological outcome using luteinizing hormone-releasing hormone agonist preoperatively compared to surgery alone. Of 28 men undergoing immediate radical retropubic prostatectomy 23 had organ-confined (17) or specimen-confined (6) disease versus 22 of 28 who received luteinizing hormone-releasing hormone neoadjuvant therapy for 12 weeks preoperatively (16 with organ-confined and 6 with specimen-confined disease, p = 1.00). In addition, when the study population was analyzed by pretreatment prostate specific antigen (PSA) levels (10 ng./ml. or less, or greater than 10 ng./ml/) there was also no difference in pathological outcome (p = 0.65 for PSA greater than 10 and p = 0.32 for PSA less than 10).\n Neoadjuvant androgen ablation therapy for 12 weeks before radical prostatectomy in patients with clinically localized adenocarcinoma of the prostate does not result in improved pathological outcomes.", "To assess the efficacy and the tolerability of flutamide as adjuvant treatment after radical prostatectomy for locally advanced, lymph node-negative prostate cancer.\n Men with locally advanced, lymph node-negative prostate cancer were randomized after radical prostatectomy to receive either flutamide 750mg daily or no adjuvant treatment. Recurrence-free and overall survival were the study end points. Recurrence was defined as a PSA value greater than 5ng/ml or two values greater than 2ng/ml more than three months apart with increasing tendency or three values greater than 1ng/ml more than three months apart with increasing tendency or any clinical recurrence.\n 309 patients (157 in the control arm and 152 in the flutamide arm) were eligible for efficacy analysis. The median follow-up was 6.1 years. Recurrence-free survival was better in the flutamide group ( P=0.0041), there was, however, no detectable difference in overall survival ( p=0.92 ). Moreover, there was a considerable toxicity reported in the flutamide group.\n Although having some effect on disease recurrence, adjuvant flutamide treatment does not improve median-term overall survival after radical prostatectomy for locally advanced, lymph node-negative prostate cancer.", "To evaluate the effect of 3 months vs. 8 months of neoadjuvant hormonal therapy before conventional dose radiotherapy (RT) on disease-free survival using prostate-specific antigen PSA and biopsies as end points for clinically localized prostate cancer.\n Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before conventional-dose RT (66 Gy) at four participating centers. The median patient age was 72 years (range, 50-84 years). The stage distribution was 17% T1c, 35% T2a, 34% T2b-T2c, 13% T3-T4. The Gleason score (GS) was < or =6 in 51%, 7 in 38%, and 8-10 in 11%. The median baseline PSA level was 9.7 ng/mL (range, 1.3-189 ng/mL). Of the 378 men, 26% were low risk (Stage T1c-T2a, GS < or =6, PSA <10 ng/mL), 43% were intermediate risk (Stage T2b or GS 7 or PSA 10-20 ng/mL), and 31% were high risk (Stage T3 or GS 8-10 or PSA >20 ng/mL). The two arms were balanced in terms of age, GS, T stage, risk group, and presenting PSA level. The median follow-up was 44 months (range, 10-84 months), and 361 patients were available for evaluation.\n The 8-month arm achieved a lower PSA level before starting RT (0.37 vs. 0.74 ng/mL, p < or =0.001) and had a greater downsizing of the prostate (mean volume 26.6 cm(3) vs. 30.5 cm(3), p < or =0.001). However, the actuarial freedom from failure rate (biochemical by American Society for Therapeutic Radiology and Oncology definition, local or distant) for the 3-month vs. 8-month arms at 3 years was 66% vs. 68% and by 5 years was 61% vs. 62%, respectively (p = 0.36). No statistically significant difference was noted in the types of failure between the two arms (crude final status): biochemical, 22.2% vs. 22.3%; local, 10.2% vs. 6.5%; and distant, 3.4% vs. 4.4% (p = 0.61). Two-year post-RT biopsies were done in 57% (n = 205). Negative biopsies were obtained in 68% of the 3-month and 77% of the 8-month patients; 18% and 14% had indeterminate biopsies and 14% and 9% were positive for residual cancer (p = 0.34) in the two arms, respectively. The median PSA level for nonfailing patients was 0.50 ng/mL in both the 3-months and 8-month arms. A suggestion of improvement was found in the 8-month arm for disease-free survival at 5 years for high-risk patients (39% vs. 52%) but did not achieve statistical significance.\n A longer period of neoadjuvant hormonal therapy before standard-dose RT does not appear to confer a benefit in terms of disease-free survival or to alter failure patterns. Failure was delayed in the 8-month arm, but this advantage was lost by 5 years of follow-up. A suggestion of benefit was noted with a longer period of hormonal therapy for high-risk patients.", "To evaluate the long-term effects of 3-month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer.\n We report the results of 402 patients (220 with a clinical T2 tumor and 182 with a clinical T3 tumor) of whom 192 randomly received neoadjuvant total androgen deprivation using a LHRH analogue (goserelin) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only.\n 'Clinical downstaging' was seen in 30% of cases in the neoadjuvantly treated group (NEO). 'Pathological downstaging' occurred in 7 and 15% of cases in the direct radical prostatectomy (DP) group and the NEO group, respectively (p<0.01). In patients with clinical T2 as well as in patients with clinical T3 tumors, a significant difference in the number of positive margins was shown in favor of the NEO group (cT2, p<0.01; cT3, p = 0.01). This advantage, although there was a trend in favor of the NEO group, specifically in cT2 tumors, did not translate in a significantly better PSA progression rate (p = 0.18). However, when evaluating the local control rate in cT2 tumors, we observed local recurrence in 3 of 102 (3%) patients in the NEO group versus 12 of 114 (11%) patients in the DP group. The difference is statistically significant (p = 0.03). In the cT3 group, this difference was not statistically significant (NEO group: 15 of 87 (17%), and DP group: 21 of 95 (22%) patients; p = 0.41).\n In this study, the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate. However, this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors. Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients. Unfortunately, this article reports a study which is not yet mature enough to show relevant information. Presently, neoadjuvant therapy should not be given outside clinical research settings.", "To assess the effect of neoadjuvant hormone treatment before radical prostatectomy on: tumor/prostate volume, prostate-specific antigen (PSA) and testosterone levels, surgical margin status and tumor stage, and the ease of surgery following treatment.\n Patients with clinically localized prostatic carcinoma were randomized to receive leuprolide acetate depot 3.75 mg once a month for 3 months and cyproterone acetate 300 mg once a week for 3 weeks prior to surgery (group A). A control group of patients had surgery without any pretreatment (group B).\n 167 patients were evaluated for the efficacy parameters. In group A, 31% of patients had a reduction in tumor/prostate volume following hormone therapy. PSA and testosterone levels were significantly reduced (p = 0.0001) in patients in group A compared to basal values. Centralized histopathological data evaluated in 145 patients (group A and 75 group B) showed that more patients in group B had tumors at stages T3A and T3B than in group A; this difference was close to significance (p = 0.057). Positive surgical margins were more common in group B (60% of patients) compared to group A (39% of patients). Similarly lymph node involvement was more common in group B compared to group A (11 versus 3%). There was little difference between the 2 study groups for the other surgical parameters assessed (ease of dissection, duration of surgery, blood loss).\n Neoadjuvant hormone therapy before radical prostatectomy has some effects in the treatment of prostate cancer. However, long-term follow-up of patients is needed to assess the impact of this therapy on morbidity and mortality.\n Copyright 2004 S. Karger AG, Basel", "Seventy-eight patients with clinical Stage C adenocarcinoma of the prostate were prospectively randomized to receive either radiation alone or radiation and adjuvant estrogen (diethylstilbestrol). No patient had received any prior definitive treatment for cancer. Forty patients were randomized to receive radiotherapy only and 38 patients to receive radiotherapy and estrogen. The median follow-up for all surviving patients was 14.5 years. Whether analyzed according to the original randomization or according to the treatment actually received, disease-free survival in the adjuvant estrogen group was strikingly and significantly higher than in the radiation-only group. At 5, 10, and 15 years patients receiving adjuvant estrogen had respective disease-free survival rates of 71%, 63%, and 63% compared with 49%, 43%, and 35% in patients having radiation only (p = 0.008). However, because of greater intercurrent disease-related mortality in patients receiving estrogen, there was no improvement in survival. This study suggests that a prospective randomized evaluation of early androgen deprivation with orchiectomy or with one of the nonestrogenic agents should be undertaken and that patients receiving early androgen deprivation should not be included in series reporting on the curative potential of radiation as a single modality.", "To test the hypothesis that androgen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may, by reducing tumor bulk and enhancing tumor cell kill, improve locoregional control and ultimately survival.\n The study was conducted from 1987 to 1991. Eligible patients were those with bulky tumors (T2--T4) with or without pelvic lymph node involvement and without evidence of distant metastases. They were randomized to receive goserelin, 3.6 mg every 4 weeks; and flutamide, 250 mg t.i.d. for 2 months before radiation therapy and during radiation therapy (Arm I), or radiation therapy alone (Arm II). Of 471 randomized patients, 456 were evaluable: 226 on Arm I and 230 on Arm II.\n As of November 1999, the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients. At 8 years, androgen ablation has been associated with an improvement in local control (42% vs. 30%, p = 0.016), reduction in the incidence of distant metastases (34% vs. 45%, p = 0.04), disease-free survival (33% vs. 21%, p = 0.004), biochemical disease-free survival = PSA <1.5 (24% vs. 10%, p < 0.0001), and cause-specific mortality (23% vs. 31%, p = 0.05). However, subset analysis indicates that the beneficial effect of short-term androgen ablation appears preferentially in patients with Gleason score 2--6. In that population, there is a highly significant improvement in all endpoints, including survival (70% vs. 52%, p = 0.015). In patients with Gleason 7--10 tumors, the regimen has not resulted in a significant enhancement in either locoregional control or survival.\n In patients with Gleason score 2--6 carcinoma of the prostate, a short course of androgen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control, reduction in disease progression, and overall survival.", "Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT).\n Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression.\n Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p <0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p <0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm.\n In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival. The improvement in survival appeared preferentially in patients with a Gleason score of 7-10.", "Androgen deprivation is an established treatment regimen for disseminated prostate cancer; however, its role in patients with localised cancer is less clear. We did a large randomised controlled trial to determine whether 3 months or 6 months of androgen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer.\n 818 men with locally advanced prostate cancer were randomly assigned to: no androgen deprivation (ie, radiotherapy alone: 66 Gy in 33 fractions of 2 Gy per day over 6.5-7.0 weeks to the prostate and seminal vesicles); 3 months' androgen deprivation with 3.6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy (same regimen as control group); or 6 months' androgen deprivation, with the same regimen, starting 5 months before radiotherapy (same regimen as control group). Primary endpoints were time to local failure and prostate-cancer-specific survival; secondary endpoints were distant failure, disease-free survival, and freedom from salvage treatment. Analyses were done by intention to treat.\n 802 (98%) patients were eligible for analysis. Median follow-up was 5.9 years (range 0.1-8.5). Compared with patients assigned no androgen deprivation, those assigned 3 months' treatment had significantly improved local failure (hazard ratio [HR] 0.56 [95% CI 0.39-0.79], p=0.001), biochemical failure-free survival (0.70 [0.56-0.88], p=0.002), disease-free survival (0.65 [0.52-0.80], p=0.0001), and freedom from salvage treatment (0.73 [0.56-0.96], p=0.025). 6 months' androgen deprivation significantly improved local failure (0.42 [0.28-0.62], p<0.0001), biochemical failure-free survival (0.58 [0.46-0.74], p<0.0001), disease-free survival (0.56 [0.45-0.69], p<0.0001), freedom from salvage treatment (0.53 [0.40-0.71], p<0.0001), distant failure (0.67 [0.45-0.99], p=0.046) and prostate-cancer-specific survival (0.56 [0.32-0.98], p=0.04) compared with no androgen deprivation.\n 6 months' androgen deprivation given before and during radiotherapy improves the outlook of patients with locally advanced prostate cancer. Further follow-up is needed to estimate precisely the size of survival benefits. Increased radiation doses and additional periods of androgen deprivation might lead to further benefit.", "We evaluated the benefits and sequencing of androgen suppression (AS) administered with external beam radiation therapy (EBRT) in T2-T3 prostate cancers.\n Between 1990 and 1999, 481 patients were entered in 2 successive, prospective, randomized studies, including 161 in the study 1 and 325 in study 2. Eligible patients had clinical stages T2-T3 prostate cancer. In the first study (L-101) subjects were randomly allocated among EBRT alone (group 1), EBRT preceded by 3 months of AS (group 2), and neoadjuvant, concomitant and adjuvant AS for a total of 10 months (group 3). In the second study (L-200) we analyzed neoadjuvant and concomitant AS (total 5 months) vs neoadjuvant, concomitant and short course adjuvant (total 10 months) AS with EBRT. In each study we used a total AS (a luteinizing hormone-releasing hormone agonist plus an antiandrogen) and a standard dose of radiation therapy at that time. Patient characteristics were well balanced in regard to age, stage, prostate specific antigen and Gleason score. No biochemical evidence of disease (BNED) was defined as an end point according to the Vancouver rule.\n In the study 1 at a median followup of 5 years 7-year biochemical-free survival rates were 42%, 66% and 69% in groups 1 to 3, respectively. BNED was significantly different between groups 1 and 2 (p = 0.009) and between groups 1 and 3 (p = 0.003) but not between groups 2 and 3 (p = 0.6). Multivariate analysis using a Cox proportional hazards model showed an HR of 6.1 for Gleason score (p = 0.001), 1.4 for PSA (p = 0.002), 0.5 for group 1 vs group 2 (p = 0.01) and 0.35 for group 1 vs group 3 (p = 0.008). In study 2 BNED at 4 years was 65%. There was no significant difference between arms 1 and 2 (p = 0.55).\n The analysis of study 1 shows a benefit of using a short course of neoadjuvant AS with EBRT vs EBRT alone for localized T2-T3 prostate cancers. Moreover, in each study adding a short course of adjuvant AS after neoadjuvant 1 provided no more advantage in these patients.", "In most clinical trials that have investigated the potential beneficial effects of neoadjuvant combined androgen blockade (CAB) in clinically localized prostate cancer, CAB has been given for 3 months, but no data are available on the influence of a longer duration of neoadjuvant CAB on the pathologic features of prostate cancer.\n Prostatectomy specimens of 40 patients, randomized to 3 (n = 18) or 6 (n = 22) months of neoadjuvant CAB, were blindly evaluated with regard to tumor volume, pathologic stage, and surgical margins. The morphologically most vital tumor areas were investigated for nucleolar size and MIB-1 defined proliferative activity.\n The patients treated for 6 months had a median tumor volume 60% lower than the 3-month treatment group (P = 0.005). In the 6-month treatment group, no residual tumor could be found in 2 cases, but the proportion of prostatectomy specimens with seminal vesical invasion and positive surgical margins was not statistically different from that after 3 months. Compared with untreated controls, tumor proliferative activity assessed by MIB-1 immunoreactivity was significantly lower at 3 and 6 months of neoadjuvant CAB (P = 0.01). However, in 2 of 1 7 examined tumors that had been treated for 6 months, high MIB-1 scores suggested a development toward therapy-resistant cancer.\n Prolonged neoadjuvant CAB for 6 months leads to a further decrease in prostatic tumor volume compared with the findings after 3 months. In a few instances, residual tumor areas with substantial MIB-1 defined proliferative activity persist at 6 months, thus indicating that in at least some cases, despite the overall decrease in tumor size, cancer cells can continue the cell cycle under CAB.", "Because the optimal timing of the institution of antiandrogen therapy for prostate cancer is controversial, we compared immediate and delayed treatment in patients who had minimal residual disease after radical prostatectomy.\n Ninety-eight men who underwent radical prostatectomy and pelvic lymphadenectomy and who were found to have nodal metastases were randomly assigned to receive immediate antiandrogen therapy, with either goserelin, a synthetic agonist of gonadotropin-releasing hormone, or bilateral orchiectomy, or to be followed until disease progression. The patients were assessed quarterly during the first year and then semiannually.\n After a median of 7.1 years of follow-up, 7 of 47 men who received immediate antiandrogen treatment had died, as compared with 18 of 51 men in the observation group (P=0.02). The cause of death was prostate cancer in 3 men in the immediate-treatment group and in 16 men in the observation group (P<0.01). At the time of the last follow-up, 36 men in the immediate-treatment group (77 percent) and 9 men in the observation group (18 percent) were alive and had no evidence of recurrent disease, including undetectable serum prostate-specific antigen levels (P<0.001). In the observation group, the disease recurred in 42 men; 13 of the 36 who were treated had a complete response to local treatment or hormonal therapy (or both), 16 died of prostate cancer, and 1 died of another disease. The remaining men in this group were alive with progressive disease at the time of the last follow-up or had had a recent relapse. Except for the treatment group (immediate therapy or observation), no clinical or histologic characteristic significantly influenced the outcome.\n Immediate antiandrogen therapy after radical prostatectomy and pelvic lymphadenectomy improves survival and reduces the risk of recurrence in patients with node-positive prostate cancer.", "To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study.\n Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade.\n Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment.\n Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.", "A prospective phase 3 trial was initiated to determine whether 8 compared with 3-month neoadjuvant hormonal therapy reduces prostate specific antigen (PSA) recurrence rates after radical prostatectomy. Our interim analysis includes secondary end points of differences in biochemistry, pathology and adverse events between the 2 groups.\n Men with clinically confined prostate cancer were randomized to receive 7.5 mg. leuprolide intramuscularly monthly and 250 mg. flutamide orally 3 times daily for 3 or 8 months before radical prostatectomy. Our study was powered to detect a 35% decrease in PSA recurrence, assuming a 30% recurrence rate in the 3-month arm after 3 years.\n A total of 547 men were randomized between August 1995 and April 1998. Men in the 8 and 3-month groups were equally stratified for T stage (29% T1c, 70% T2), Gleason grade (68% less than 4, 32% 4 or greater) and pretreatment PSA (63% less than 10, 27% 10 to 20 and 10% greater than 20 microg./l.). Mean pretreatment PSA was slightly higher in the 8-month compared with the 3-month group (11.64 versus 9.95 microg./l., respectively, p = 0.0539). A total of 44 men withdrew from study before surgery and, therefore, were nonevaluable. Preoperative PSA nadir was less than 0.1 microg./l. in 43.3% versus 75.1% (p <0.0001), and 0.3 microg./l. or greater in 21% versus 9.2% after 3 versus 8 months, respectively (p <0.0006). Mean serum PSA decreased 98% to 0.12 microg./l. after 3 months, with a further 57% to 0.052 microg./l. from 3 to 8 months. Transrectal ultrasound determined that prostatic volume decreased 37% from a mean of 40.6 to 25.4 cc after 3-month neoadjuvant hormonal therapy (p = 0.0001) and a further 13% to 22.2 cc after 8 months (p = 0.03). Mean hemoglobin decreased 15% (148.2 to 125.4 gm./dl.) after 3-month neoadjuvant hormonal therapy but stabilized thereafter. Radical prostatectomy was completed in 500 men, while surgery was aborted intraoperatively in 3. Positive margin rates were significantly lower in the 8 than 3-month group (12% versus 23%, respectively, p = 0.0106). There were no fatal adverse events and no differences between the 2 groups in the severity or causality (p = 0.287, 0.0564) of adverse events, or incidence of increased liver enzymes or diarrhea (p = 0.691, 0.288, respectively). However, men in the 8-month group noticed a higher number of newly reported adverse events (4.5 versus 2.9, p <0.0001) and higher incidence of hot flushes than the 3-month group (87% versus 72%, respectively, p <0.0001).\n Ongoing biochemical and pathological regression of prostate tumors occurs between 3 and 8 months of neoadjuvant hormonal therapy, suggesting that the optimal duration of neoadjuvant hormonal therapy is longer than 3 months. Longer followup is needed to determine whether longer therapy alters PSA recurrence rates.", "The ongoing Early Prostate Cancer (EPC) programme is assessing bicalutamide ('Casodex') 150 mg, either alone or as adjuvant to treatment of curative intent, in patients with localised or locally advanced prostate cancer (n=8113). This paper presents an exploratory analysis of the subgroup of the EPC programme who received radiotherapy with curative intent (n=1370) in order to determine the efficacy (in terms of progression-free survival [PFS]) and tolerability of bicalutamide 150 mg in this setting.\n 1370 patients with T1-4, MO, any N prostate cancer received bicalutamide 150 mg or placebo adjuvant to radiotherapy of curative intent. This analysis was undertaken at median 5.3 years' follow-up.\n In patients with locally advanced disease (n=305), bicalutamide adjuvant to radiotherapy significantly increased PFS by 53% (event-time ratio 1.53; 95% confidence intervals [CI] 1.16, 2.02) compared with placebo and reduced the risk of disease progression by 42% (hazard ration [HR] 0.58; 95% CI 0.41, 0.84; P=0.00348). In these patients, objective progression was experienced by 33.5% of those randomised to bicalutamide versus 48.6% for those randomised to placebo. The between-group difference in patients with localised disease (n=1065) failed to reach statistical significance (HR 0.80; 95% CI 0.62, 1.03; P=0.088). The most common adverse events were breast pain (74.8%) and gynaecomastia (66.6%), which were mild to moderate in >90% of cases.\n Bicalutamide 150 mg/day given as adjuvant to radiotherapy significantly improved PFS in patients with locally advanced prostate cancer. For patients with localised disease, the results at this stage from the radiotherapy subgroup and the overall EPC programme suggest that adjuvant hormonal therapy is currently not appropriate. There were no unexpected tolerability findings.", "To assess the effect of neoadjuvant combination therapy with the antiandrogen flutamide and a luteinizing-hormone-releasing hormone (LHRH) agonist administered for 3 months before radical prostatectomy, compared with surgery alone in early stage prostate cancer on histopathologic findings at surgery and serum prostate-specific antigen (PSA).\n A sample of 161 randomly screened patients diagnosed as having stage B (134 patients) or C (27 patients) prostate cancer were randomly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the antiandrogen flutamide and an LHRH agonist before radical prostatectomy.\n Neoadjuvant combination therapy before radical prostatectomy decreased cancer-positive surgical margins from 33.8% in the control group to only 7.8%, thus leaving 92.2% of patients with negative margins at surgery. A net 54% improvement of staging was observed in favor of combination therapy. Organ-confined disease, on the other hand, increased from 49.3% to 77.8% of patients after 3 months of combination therapy, for a 57.8% increase in the incidence of organ-confined disease. No cancer was found in 6 (6.7%) prostatectomy specimens from the treated group. A close correlation was found between serum PSA at diagnosis and the stage of the disease at surgery. Upstaging increased from 30% at serum PSA values of 0 to 3.0 ng/mL up to 100% at serum PSA values above 15 ng/mL.\n Although long-term follow-up of these patients is required to determine the impact on survival, the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer.", "To determine the acceptability of short term neo-adjuvant maximal androgen deprivation (MAD) to patients treated with external beam radiation for locally advanced prostate cancer.\n Between 1996 and 2000, 818 patients with locally advanced, but non-metastatic, prostate cancer were entered into a randomised clinical trial (TROG 96.01), which compared radiation treatment alone with the same radiation treatment and 3 or 6 months neo-adjuvant MAD with goserelin and flutamide. Relevant symptoms, and how troublesome they were to the patient, were scored using a self-assessment questionnaire. This was completed by the patient at registration, and at specified times during and after treatment. Patients taking flutamide had liver function tests checked at regular intervals.\n All patients have completed at least 12 months follow-up after treatment. Nearly all patients completed planned treatment with goserelin, but 27% of patients in the 6-month MAD treatment arm, and 20% in the 3-month arm, had to stop flutamide early. This was mainly due to altered liver function (up to 17% patients) and bowel side effects (up to 8% patients). However, although flutamide resulted in more bowel symptoms for patients on MAD, there was significant reduction in some urinary symptoms on this treatment. Acute bowel and urinary side effects at the end of radiation treatment were similar in all treatment arms. Side effect severity was unrelated to radiation target volume size, which was reduced by MAD, but symptomatology prior to any treatment was a powerful predictor. Of the 36% of patients who were sexually active before any treatment, the majority became inactive whilst on MAD. However, sexual activity at 12 months after radiation treatment was similar in all treatment arms, indicating that the effects of short term MAD on sexual function are reversible.\n Despite temporary effects on sexual activity, and compliance difficulties with flutamide, short-term neo-adjuvant MAD was not perceived by patients to be a major inconvenience. If neo-adjuvant MAD in the way tested can be demonstrated to lead to improved biochemical control and/or survival, then patients would view these therapeutic gains as worthwhile. Compliance with short-term goserelin was excellent, confirming that LH-RH analogues have a potential role in more long-term adjuvant treatment. However, for more protracted androgen deprivation, survival advantages and deleterious effects need to be assessed in parallel, in order to determine the optimal duration of treatment.", "To investigate the outcome of neo-adjuvant hormone treatment before radical prostatectomy regarding local tumour extension, peri-operative blood loss and operation time.\n Of 111 surgically treated patients with prostate cancer (T1b-T3a, N0, M0, G1-3), 55 were randomised to immediate radical prostatectomy and 56 to 3 months of neo-adjuvant treatment with triptorelin (3.75 mg i.m. every 28 days) and cyproterone acetate (50 mg b.i.d. for 3 weeks to prevent flare).\n No differences were found in blood loss or operation time but patients who had neo-adjuvant treatment had a significantly lower frequency of positive margins (41 vs. 23%, p = 0.013). Conclusion: Neo-adjuvant treatment does not facilitate radical prostatectomy but may improve the chance of local cure. This must, however, be documented with long-term follow-up in randomised patients.", "In 1992 we initiated a national randomized prospective trial of 3 months of cyproterone acetate before radical prostatectomy compared to prostatectomy alone. Initial results indicated a 50% decrease in the rate of positive surgical margins. This decrease did not translate into a difference in prostate specific antigen (PSA) progression at 3 years. This report is on the long-term outcome (median followup 6 years) of this cohort.\n This prospective, randomized, open label trial compared 100 mg cyproterone acetate 3 times daily for 3 months before surgery to surgery alone. Randomization occurred between January 1993 and April 1994. Patients were stratified according to clinical stage, baseline serum PSA and Gleason sum. A total of 213 patients were accrued. Biochemical progression was defined as 2 consecutive detectable PSAs (greater than 0.2 ng/ml) at least 4 weeks apart, re-treatment or death from prostate cancer.\n A total of 34 (33.6%) patients undergoing surgery only and 42 (37.5%) patients given neoadjuvant hormone therapy (NHT) had biochemical recurrence during the median followup of 6 years. Despite the significant pathological down staging in this study, there was no significant difference in number of patients with no evidence of biochemical disease (bNED) survival (p = 0.732). A bNED survival benefit favoring NHT was seen in men with a baseline PSA greater than 20 (p = 0.015).\n After 6 years of followup there was no overall benefit with 3 months of NHT. Improved bNED survival was seen in the highest risk PSA group (PSA greater than 20). The possibility that high risk patients may benefit from NHT warrants further investigation.", "In the initial report of the Lupron Depot Neoadjuvant Prostate Cancer Study Group patients who received 3 months of androgen deprivation had a significant decrease in the positive margin rate. We monitored these patients for 5 years and to our knowledge present the longest followup of any neoadjuvant trial.\n A multi-institutional prospective randomized trial was performed between February 1992 and April 1994 involving patients with stage cT2b prostate cancer, including 138 who received 3 months of leuprolide plus flutamide before radical prostatectomy and 144 who underwent radical prostatectomy only. Patients were followed every 6 months with serum prostate specific antigen (PSA) testing for 5 years. Biochemical recurrence was defined as PSA greater than 0.4 ng./ml.\n At 5 years there was no difference in the biochemical recurrence rate. PSA was less than 0.4 ng./ml. in 64.8% of the patients in the neoadjuvant androgen ablation plus prostatectomy and 67.6% in the prostatectomy only group (p = 0.663).\n Although 3 months of androgen deprivation before radical prostatectomy resulted in an apparently significant decrease in positive surgical margins, a 5-year followup does not indicate any difference in the recurrence rate. Until studies document improvement in biochemical or clinical recurrence with longer periods of treatment, induction androgen deprivation before radical prostatectomy is not indicated." ]

[ "2965809", "12072853", "3628103", "2285093", "15668775", "15682005" ]

[ "Shoe insoles in the workplace.", "Can custom-made biomechanic shoe orthoses prevent problems in the back and lower extremities? A randomized, controlled intervention trial of 146 military conscripts.", "Effect of viscoelastic insoles on pain.", "Prevention of common overuse injuries by the use of shock absorbing insoles. A prospective study.", "The effect of insoles on the incidence and severity of low back pain among workers whose job involves long-distance walking.", "A controlled randomized study of the effect of training with orthoses on the incidence of weight bearing induced back pain among infantry recruits." ]

[ "Ninety-six women participated in a crossover study to evaluate the effectiveness of viscoelastic polyurethane insoles in reducing back, leg, and foot pain among adults who spend the majority of each work day standing. Twenty-five of the subjects reported that the insoles made their shoes too tight to be comfortable. The remainder, however, found the insoles very comfortable (P less than .002, Wilcoxon, signed-rank test) and reported significant reductions in back pain (P less than .02), foot pain (P less than .03), and leg pain (P less than .007). When these subjects were asked whether they would prefer to wear their shoes alone or with insoles, the preference for insoles was overwhelming (P less than .007, back; P less than .03, leg; and P less than .009, foot pain). It is concluded that viscoelastic insoles can effectively improve comfort and reduce back, leg, and foot pain in individuals who must stand throughout the day.", "Shock-absorbing and biomechanic shoe orthoses are frequently used in the prevention and treatment of back and lower extremity problems. One review concludes that the former is clinically effective in relation to prevention, whereas the latter has been tested in only 1 randomized clinical trial, concluding that stress fractures could be prevented.\n To investigate if biomechanic shoe orthoses can prevent problems in the back and lower extremities and if reducing the number of days off-duty because of back or lower extremity problems is possible.\n Prospective, randomized, controlled intervention trial.\n One female and 145 male military conscripts (aged 18 to 24 years), representing 25% of all new conscripts in a Danish regiment.\n Health data were collected by questionnaires at initiation of the study and 3 months later. Custom-made biomechanic shoe orthoses to be worn in military boots were provided to all in the study group during the 3-month intervention period. No intervention was provided for the control group. Differences between the 2 groups were tested with the chi-square test, and statistical significance was accepted at P <.05. Risk ratio (RR), risk difference (ARR), numbers needed to prevent (NNP), and cost per successfully prevented case were calculated.\n Outcome variables included self-reported back and/or lower extremity problems; specific problems in the back or knees or shin splints, Achilles tendonitis, sprained ankle, or other problems in the lower extremity; number of subjects with at least 1 day off-duty because of back or lower extremity problems and total number of days off-duty within the first 3 months of military service because of back or lower extremity problems.\n Results were significantly better in an actual-use analysis in the intervention group for total number of subjects with back or lower extremity problems (RR 0.7, ARR 19%, NNP 5, cost 98 US dollars); number of subjects with shin splints (RR 0.2, ARR 19%, NNP 5, cost 101 US dollars); number of off-duty days because of back or lower extremity problems (RR 0.6, ARR < 1%, NNP 200, cost 3750 US dollars). In an intention-to-treat analysis, a significant difference was found for only number of subjects with shin splints (RR 0.3, ARR 18%, NNP 6 cost 105 US dollars), whereas a worst-case analysis revealed no significant differences between the study groups.\n This study shows that it may be possible to prevent certain musculoskeletal problems in the back or lower extremities among military conscripts by using custom-made biomechanic shoe orthoses. However, because care-seeking for lower extremity problems is rare, using this method of prevention in military conscripts would be too costly. We also noted that the choice of statistical approach determined the outcome.", "The purpose of this study was to assess the effect of viscoelastic shoe inserts on pain in nursing students. Students (N = 100) were randomly assigned to control and viscoelastic groups. The viscoelastic group used viscoelastic insoles in their work shoes for five weeks. A pain questionnaire was used to measure location and intensity of post-work pain. The questionnaire was administered as a pre-test and after five weeks. Post-test comparisons between groups indicated significant differences which were not present at pre-test. The viscoelastic group reported a significant peripheral shift in pain location from back to lower extremity; the viscoelastic group also showed significant changes in duration of post-work pain and frequency of pain during the workday. The clinical efficacy of viscoelastic shoe inserts for modifying weight bearing-induced back pain is supported. Further clinical research into the therapeutic and prophylactic value of shock-attenuating shoe inserts for healthy as well as patient populations is advocated.", "Sedentary individuals, particularly new military recruits, who start a physical training program have a substantial risk of developing an overuse injury of the lower limb. In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training. The experimental group consisted of 237 randomly selected new recruits, while 1151 recruits were the control group. Insoles were given to the experimental group and compliance was monitored. A panel of doctors documented and classified all injuries occurring during the 9 week period. A total of 54 (22.8%) and 237 (31.9%) injuries were reported in the experimental and control groups, respectively. In both groups, the majority of injuries were overuse (experimental group, 90.7%; control group, 86.4%). The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower (P less than 0.05) in the experimental group. The mean incidence of stress fractures was lower in the experimental group but not significantly so (0.05 less than P less than 0.1). This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles.", "The prevalence and incidence of low back pain in general society is high. Workers whose job involves walking long distances have an even higher tendency to suffer from low back pain. A positive effect of insoles in reducing low back pain was found in professional sports players. This was not examined on people whose job involves walking long distances. In this double blind prospective study we examined the effectiveness of insoles constructed in a computerized method to placebo insoles in 58 employees whose work entailed extensive walking and who suffered from low back pain. The evaluation was performed by the MILLION questionnaire, which is considered as a valid questionnaire for evaluation of low back pain. We calculated the differences of the pain intensity before and after the intervention, in the employees using the insoles manufactured by computer in comparison to the users of the placebo insoles. In each group, the analysis was performed in comparison to the baseline. A total of 81% of the employees preferred the real insoles as effective and comfortable in comparison to 19% of the users of the placebo insoles (P<0.05). The results of this study indicate a substantial improvement in the low back pain after the use of the true insoles. The average pain intensity according to the MILLION questionnaire before the use of the insoles was 5.46. However, after the use of the real insoles and the placebo insoles, the average pain intensity decreased to 3.96 and 5.11, respectively. The difference of the average pain intensity at the start of the study and after the use of the real insoles was significant: -1.49 (P=0.0001), whereas this difference after the use of the placebo insoles was not significant: -0.31 (P=0.1189). The reported severity of pain also decreased significantly: a level 5 pain and above was reported by 77% of the subjects at the start of the study. After the use of the real insoles only 37.9% of the subjects reported a similar degree of pain severity, and 50% of the subjects did so after the use of the placebo insoles (P< 0.05). We did not find a link between low back pain and other variables such as gender, age, number of offspring, work seniority, smoking, previous use of insoles and previous medication. This study demonstrates that the low back pain decreased significantly after the use of real insoles compared to placebo ones.", "Randomized controlled trial.\n To determine if the use of custom shoe orthoses can lessen the incidence of weight bearing-induced back pain.\n The scientific basis for the use of orthoses to prevent back pain is based principally on studies that show that shoe orthoses can attenuate the shock wave generated at heel strike. The repetitive impulsive loading that occurs because of this shock wave can cause wear of the mechanical structures of the back. Previous randomized studies showed mixed results in preventing back pain, were not blinded, and used orthoses for only short periods of time.\n A total of 404 eligible new infantry recruits without a history of prior back pain were randomly assigned to received either custom soft, semirigid biomechanical, or simple shoe inserts without supportive or shock absorbing qualities. Recruits were reviewed biweekly by an orthopaedist for back signs and symptoms during the course of 14 weeks of basic training\n The overall incidence of back pain was 14%. By intention-to treat and per-protocol analyses, there was no statistically significant difference between the incidence of either subjective or objective back pain among the 3 treatment groups. Significantly more recruits who received soft custom orthoses finished training in their assigned orthoses (67.5%) than those who received semirigid biomechanical orthoses (45.5%) or simple shoe inserts (48.6%), P = 0.001.\n The results of this study do not support the use of orthoses, either custom soft or semirigid biomechanical, as prophylactic treatment for weight bearing-induced back pain. Custom soft orthoses had a higher utilization rate than the semirigid biomechanical or simple shoe inserts. The pretraining physical fitness and sports participation of recruits were not related to the incidence of weight bearing-induced back pain." ]

[ "7793195", "7072998", "4942713", "6696214", "19943458", "8291726", "378022", "4837206", "12411035", "4895338", "7193989", "17158129", "4014617", "8001404", "15636826", "2378593" ]

[ "Desflurane analgesia for vaginal delivery.", "Neonatal neurobehavioral effects of inhalation analgesia for vaginal delivery.", "Comparison between nitrous oxide and methoxyflurane for obstetrical analgesia.", "Enflurane as an analgesic in labour.", "Entonox for labor pain: a randomized placebo controlled trial.", "Nitrous oxide in early labor. Safety and analgesic efficacy assessed by a double-blind, placebo-controlled study.", "Self-administered intermittent nitrous oxide analgesia for labour. Enhancement of effect with continuous nasal inhalation of 50 per cent nitrous oxide (Entonox).", "[Methoxyflurane (Penthrane) or nitrous oxide as agents of analgesia in childbirth?].", "Clinical study on labor pain relief using the combined spinal-epidural analgesia and inhaling nitrous oxide.", "Methoxyflurane and nitrous oxide as obstetric analgesics. I. A comparison by continuous administration.", "Enflurane analgesia in obstetrics.", "Analgesia with sevoflurane during labour: ii. Sevoflurane compared with Entonox for labour analgesia.", "Self-administered isoflurane in labour. A comparative study with Entonox.", "[Application of nitrous oxide in labor analgesia].", "Self-administered mixture of Entonox and isoflurane in labour.", "Effectiveness of transcutaneous electric nerve stimulator for pain relief in labour." ]

[ "The use of subanaesthetic concentration of inhalational anaesthetic for vaginal delivery offers many advantages to the mother and newborn. Desflurane, with the characteristics of rapid onset and minimal metabolism, may provide better analgesia and safety for labour pain control. Eighty healthy parturients were randomly assigned to receive either desflurane 1.0-4.5% and oxygen (n = 40) or nitrous oxide 30-60% in oxygen (n = 40). Analgesia was assessed using a score from 0 (no relief) to 4+ (excellent analgesia), amnesia for the delivery, blood loss were recorded. Neonates were evaluated by Apgar scores and neurologic and adaptive capacity scores (NACS). Data were analyzed for statistical significance using Student's t-test or Chi-square when appropriate. Analgesia scores were similar for both groups with more amnesia in desflurane group (23% vs 0% P < 0.05). Blood loss did not differ significantly, 364 ml for the desflurane group and 335 ml for the nitrous oxide group. There were no significant differences for neonatal Apgar score at 1 min or at 5 min or the NACS at 2 hr or 24 hr between the two groups. We conclude that desflurane in subanaesthetic doses is safe and effective inhalation agent for normal delivery but might be associated with amnesia.", "The authors studied the neonatal neurobehavioral effects of nitrous oxide:oxygen and enflurane:oxygen inhalation analgesia for vaginal delivery. Parturients were assigned randomly to receive no inhalation agent (Group 1, n = 21); enflurane, 0.3 to 0.8 per cent, and oxygen (Group 2, n = 22); or nitrous oxide, 30 to 50 per cent, and oxygen (Group 3, n = 18). Infants were tested at 15 min, 2 h, and 24 h of age using the Neurologic and Adaptive Capacity Score (NACS); and at 2 and 24 h using the Early Neonatal Neurobehavioral Scale (ENNS). No significant differences in neurobehavioral status occurred. For all groups, scores tended to be lowest at two hours of age. We conclude that neither enflurane nor nitrous oxide analgesia adversely affects neonatal neurobehavioral status at 15 min, 2 h, or 24 h of age.", "nan", "A comparison of the analgesic efficacy of enflurane 1% in air with Entonox (50% nitrous oxide in oxygen) was performed in 20 consenting women during the first stage of labour. The two drugs were given in a random sequence to each woman, who also acted as her own control. Pain scores were significantly lower with enflurane than Entonox, although drowsiness scores were higher. No untoward effects were reported with either agent. The use of enflurane as an analgesic in the first stage of labour warrants further investigation.", "This study aims to investigate the effectiveness of nitrous oxide on pain of labor contractions and on maternal SaO2. The patients were randomized to receive either a pre-prepared mixture of 50% nitrous oxide and oxygen or 50% oxygen by a coin. Study drugs started as early as the onset of pain with each contraction. The patient herself administered gases via a facemask connected to the uni-directional valve which enables the patients to breathe fresh gas in each inspiration. The gas administration was continued to the end of contraction pain at which the patient breathed the room air. Variables such as SaO2, blood pressure, pain and side effects were recorded. 534 ASA I and II parturients, aged from 16 to 35 years, scheduled for elective labor from September 2004 to 2006 were evaluated. Four patients were lost from the study. The mean age of patients was 25.5+/-4.3 years. During the first three measurements, the SaO2 was significantly higher in control group. In addition, the mean arterial pressure was comparable between groups except two first measurements in which the control group was higher. All the Visual Analogue Scale (VAS) values were significantly lower in nitrous oxide group. There were no significant differences in 1st and 5th min apgar scores between groups. All of the side effects were significantly higher among patients in nitrous oxide. In conclusion, our data indicate that using nitrous oxide 50% provides significant pain relief. Nonetheless, it is associated with few side effects, nitrous oxide can be quickly implemented during advanced painful labor.", "Intermittent self-administered nitrous oxide has long had widespread use as an analgesic in labor, but its efficacy has not been adequately established. Questions about its effect on maternal oxygenation between labor contractions also have been raised.\n Twenty-six women were recruited to participate in a randomized, double-blind, cross-over, placebo-controlled study to assess the effect of intermittent nitrous oxide inhalation on labor pain and maternal hemoglobin oxygen saturation (SPO2) during the first stage of labor. Visual analog scale pain scores for each of five consecutive labor contractions were measured after administration of either nitrous oxide or compressed air.\n Mean visual analog scale pain scores for five contractions were 5.1, 5.2, 5.7, 5.2, and 5.6 (nitrous oxide) and 4.9, 5.2, 6.1, 5.6, and 5.7 (compressed air). There were no statistically significant differences in pain when nitrous oxide as compared with compressed air was administered. Pain scores did not differ significantly over time as a function of inhaled substance (F = 0.41, P = 0.53). The mean lowest SPO2 observed between these contractions after self-administration of nitrous oxide and air were 97, 97, 97, 97, and 97% (nitrous oxide) and 97, 96, 96, 96, and 96% (compressed air). SPO2 was significantly higher after nitrous oxide administration (F = 8.8, P = 0.007).\n While intermittent self-administered 50% nitrous oxide in oxygen does not appear to predispose parturient women to hemoglobin oxygen desaturation, its analgesic effect has yet to be clearly demonstrated.", "nan", "nan", "To study the pain relief effectiveness of the combined spinal-epidural analgesia (CSEA) and the inhalation of nitrous oxide, and the influences on the mothers and infants.\n The 300 cases of pregnant women were randomly divided into 3 groups: CSEA group, nitrous oxide group and control group. The nitrous oxide group was that pregnant women inhaled nitrous oxide premixed with oxygen (50%:50%), the pregnant women of the CSEA group were injected fentanyl and bupivacaine in the subarachnoid and epidural space, analgesic was not used in the control group. The degree of labor pain, duration of the labor, way of delivery, bleeding volume, rate of anoxia of newborn, blood gas analysis to maternal radius artery and fetal umbilical blood among 3 groups were observed.\n The effect for analgesia labor of the CSEA group was much better than that of the nitrous oxide group (P < 0.01). In the first stage of labor and total stage of labor, the CSEA group was shorter than the others (P < 0.05), but there was no difference between the nitrous oxide group and the control group (P > 0.05). In the second stage of labor, the 3 groups were alike to each other. The bleeding volume of caesarean section (373 +/- 77) ml in the nitrous oxide group was much more than the other 2 groups, there was no difference between the CSEA group (259 +/- 78) ml and the control group (239 +/- 89) ml. The rate of obstetric forceps of CSEA group was higher than the control group (P < 0.01), and the rate of caesarean section of the nitrous oxide group was much higher than the CSEA group. The blood gas analysis to maternal radius artery and fetal umbilical blood and the rate of anoxia of newborn of 3 groups revealed no significant difference.\n The effectiveness of the combined spinal-epidural analgesia CSEA for analgesia labor is confirmed and has rarely side-effect, and it can be the first choice, and the inhalation of nitrous oxide can safely provide effective labor analgesia, too.", "Methoxyflurane and nitrous oxide have been compared as obstetric analgesics. The inhaled concentrations of these agents, given continuously, were adjusted by an anaesthetist to maintain each patient at the optimum state between reaction to pain and consciousness. Assessments were made continuously.Though the anaesthetist's assessment showed no difference between the mean results, a greater proportion of the methoxyflurane patients were \"satisfactory\" for 90-100% of the time than of the nitrous oxide patients, particularly in regard to objective pain relief. The midwives' opinion of those who had \"complete\" pain relief supported this. Nausea was significantly less among methoxyflurane patients, and vomiting during labour occurred only in patients who had nitrous oxide. It is concluded that nitrous oxide and methoxyflurane given in a continuously adjusted concentration are almost equally effective as obstetric analgesics, though there are certain features which favour methoxyflurane.", "The effects of enflurane analgesia (approximately 0.5%) were studied in 55 patients during the second stage of normal vaginal delivery and were compared with effects of nitrous oxide (approximately 40%) in 50 similar patients. The enflurane and oxygen mixture was rated satisfactory by 89% of the mothers and 80% of the anesthesiologists. These ratings did not differ significantly from those for nitrous oxide. Obstetricians, however, rated the enflurane and oxygen mixture superior. The newborns of mothers receiving both agents wee vigorous and comparable when assessed by Apgar scores and cord blood gas tensions. The estimate of blood loss was similar in both groups. Serum inorganic fluoride concentrations in the mother after anesthesia were not significantly increased from preanesthetic levels with either agent. There was no biochemical evidence of renal toxicity. In neonates of mothers given enflurane, the mean umbilical cord concentration of serum inorganic fluoride ions was 2.4 +/- 0.2 micromoles/L, a value well below that associated with nephrotoxicity.", "We determined the optimal inspired sevoflurane concentration for use during labour as 0.8% in our previous study. This study compared sevoflurane at a concentration of 0.8% and Entonox((R)) (nitrous oxide 50%: oxygen 50%) for analgesia during labour in 32 healthy parturients.\n Each mother underwent two open-label, three-part sequences in random order, Entonox-sevoflurane-Entonox or sevoflurane-Entonox-sevoflurane. In each part the agent was self-administered during 10 contractions. A 100 mm visual analogue scores for pain relief and sedation was completed immediately after each contraction.\n Two patients withdrew during administration of sevoflurane (because of its odour) and five during Entonox (requesting epidural analgesia). Of the remaining women, data were available for analysis from 29 participants: median (IQR [range]) pain relief scores were significantly higher for sevoflurane 67 (55-74 [33-100]) mm than for Entonox 51 (40-69.5 [13-100]) mm (P<0.037). Nausea and vomiting were more common in the Entonox group [relative risk 2.7 (95% CI 1.3-5.7); P=0.004]. No other adverse effects were observed in the mothers or babies. There was significantly more sedation with sevoflurane than with Entonox {74 (66.5-81 [32.5-100]) and 51 (41-69.5 [13-100]) mm, respectively; P<0.001}. Twenty-nine patients preferred sevoflurane to Entonox and found its sedative effects helpful.\n We conclude that self-administered sevoflurane at subanaesthetic concentration (0.8%) can provide useful pain relief during the first stage of labour, and to a greater extent than Entonox. Although greater sedative effects were experienced with sevoflurane, it was preferred to Entonox.", "Entonox (50% nitrous oxide in oxygen) and isoflurane (0.75% in oxygen) were compared as analgesics in the first stage of labour in 32 consenting women. The drugs were self-administered and given in random sequence, each during five consecutive uterine contractions. Each patient acted as her own control. Linear analogue pain scores were significantly lower (p less than 0.001) with isoflurane than with Entonox, but scores for drowsiness were higher for isoflurane. Further study is needed to assess the effects of more prolonged use of isoflurane in labour.", "Labor analgesia with nitrous oxide was studied in 34 parturients, and another 50 women taking no drug as the control group. The analgesic effect was satisfactory. By Mulleetr's pain in labor score, 91.18% women had score of 0-1, and their respiratory and circulatory functions were not affected. During inhalational analgesia the parturients remained conscious. Uterine contraction, progress of labor and neonatal Apgar score were not interferred, and postpartum bleeding was not increased. There was no complications in the treatment group. This study suggests that nitrous oxide with enough oxygen inhalation is one of the good drug for obstetric analgesia, but its concentration must be strictly controlled.", "Entonox (50% nitrous oxide premixed in oxygen) was compared with a mixture of Entonox and approximately 0.25% isoflurane (Entonox-isoflurane) for pain relief in the first stage of labour in 39 mothers. An Oxford Miniature Vaporizer was incorporated as the draw-over vaporizer for adding isoflurane to Entonox. The mixture was self-administered via the Entonox on-demand valve. The two mixtures were given in random sequence for five consecutive contractions of labour to each patient. Linear analogue pain relief scores were significantly higher (P=0.001) with Entonox-isoflurane. Fourteen patients continued using Entonox-isoflurane until delivery. No adverse effect from prolonged use was noted. Entonox-isoflurane is considered worthy of further investigation.", "The effectiveness of transcutaneous electric nerve stimulation (TENS) for pain relief in labour was compared to inhalation analgesia consisting of 50% nitrous oxide and 50% oxygen (ENTONOX). In the first part of the study 101 patients in early labour were allocated to using TENS (Group A) or ENTONOX (Group B) for pain relief. Our results did not show any beneficial effect on pain relief in labour with the use of TENS over ENTONOX; 18.8% of patients in Group A went through labour without any further form of analgesia as opposed to 17.0% in Group B. In the second part of the study 20 nulliparous patients having induced labour were randomly allocated to use TENS (Group C) or ENTONOX (Group D) as the first modality of pain relief. A switchover was made when labour pains were no longer tolerable. The results showed that both TENS and ENTONOX could be used in early labour up to 5-6 cm cervical dilatation till the frequency of contractions was nearly 5 in 10 min or the first 3-4 hr from the time patients first requested pain relief in labour when frequency of contractions was nearly 4 in 10 min. TENS could be used in early labour for patients who wish to be ambulant and is as effective as ENTONOX. Either modality of pain relief was not adequate for pain relief throughout labour." ]

[ "9703790", "16141467" ]

[ "Sodium selenite as prophylaxis against erysipelas in secondary lymphedema.", "Reduction of postoperative lymphedema after oral tumor surgery with sodium selenite." ]

[ "In a randomised, double-blind study, the efficacy of sodium selenite application in combination with physical therapy to relieve congestion was investigated in a cohort of 60 cancer patients with secondary lymphedema, with special reference to the development of the incidence of erysipelas. All of the patients investigated in this study had erysipelas infection of the skin. Selenium was administered in pharmacological doses. The duration of physical therapy was three weeks. Patients were under observation for a further three months. The incidence of erysipelas among our patients was 11%. During the three-week period of intensive treatment, there was not a single case of erysipelas in the treatment group, whereas there was one single case in the placebo group. In the follow-up period (3 months), once again there was not a single case of erysipelas in the treatment group, but 50% of the patients in the placebo group exhibited erysipelas. In spite of higher doses, the selenium level did not rise above normal values. Patients under long-term antibiotic therapy suffered no relapse when the antibiotic therapy was stopped and instead, selenium was administered. It could be shown, in addition, that by administration of a single high-dose of sodium selenite, inflammation could be immediately brought under control.", "The objective of this double-blind, randomized study was to establish whether sodium selenite administered orally or intravenously reduces postoperative lymphedema after oral tumor surgery and to study the effect of sodium selenite on glutathione peroxidase (GPX) activity and oxygen radical production. Twenty patients were enrolled in the study. Each of the participants received 1,000 microg sodium selenite intravenously or orally daily for 3 wk during the pre-, intra-, and postoperative period. The extent of lymphedema was measured for 2 wk and the plasma and whole-blood selenium concentration, GPX, reactive oxygen species (ROS), NO, and malonic dialdehyde were measured for 1 yr postoperatively. There was an inverse correlation between the severity of the lymphedema and the whole-blood/plasma selenium concentration and GPX activity. In addition, a positive correlation between the ROS concentration and the extent of lymphedema was observed. A significant reduction of lymphedema occurred in the sodium selenite-treated group. It is concluded that sodium selenite represents a suitable adjuvant treatment of secondary lymphedema in surgically treated patients with tumors in the oral and maxillofacial areas. Treatment with sodium selenite is especially advantageous as it can be instituted immediately after surgery prior to wound healing when manual lymphatic decongestion therapy cannot be applied." ]

[ "10438995", "8968783", "9804214" ]

[ "Urinary follicle-stimulating hormone (FSH) versus recombinant FSH in clomiphene citrate-resistant, normogonadotropic,chronic anovulation: a prospective randomized study.", "Clinical assessment of human gonadotrophins produced by recombinant DNA technology.", "A comparative prospective study of a chronic low dose versus a conventional ovulation stimulation regimen using recombinant human follicle stimulating hormone in anovulatory infertile women." ]

[ "To compare the efficacy and safety of urinary FSH and recombinant FSH for ovulation induction in patients with clomiphene citrate-resistant, normogonadotropic, chronic anovulation.\n Prospective, randomized trial.\n University-based infertility clinic.\n Fifty-one women.\n Subjects were randomized to receive either urinary FSH (35 patients, 64 cycles) or recombinant FSH (16 patients, 32 cycles). A maximum of three cycles using the low-dose step-up protocol with the same gonadotropin were undertaken.\n Cumulative ovulation and pregnancy rates after three cycles, total gonadotropin dose, duration of stimulation, and single follicle development rate.\n Cumulative ovulation rates were 89.3% and 93.1% for the urinary FSH and recombinant FSH groups, respectively. The threshold and total doses of FSH and the duration of stimulation were similar between the two groups. Significantly more single follicle development was noted in the recombinant FSH group. The respective clinical pregnancy rates per noncanceled cycles in the urinary FSH and recombinant FSH groups were 23.2% and 27.6%. There were three sets of twins in the urinary FSH group. No case of ovarian hyperstimulation syndrome was encountered.\n Urinary FSH and recombinant FSH are both efficient and safe for inducing ovulation with the low-dose step-up protocol.", "nan", "The efficacy and safety of a chronic low dose (group A) and a conventional (group B) stimulation regimen of recombinant human follicle stimulating hormone (r-HFSH) were compared in 103 WHO Group II infertile women with clomiphene citrate-resistant anovulation. Mono- or bifollicular development was induced in 88.1% of patients in group A compared with 76.1% in group B. Ovulation and pregnancy rates were higher in group A (71.4% and 33.3%, respectively) than in group B (63.0% and 20%), but these differences were not statistically significant. Additionally, the total number of follicles that were >10 mm diameter was lower in group A than group B (3.0+/-2.6 versus 6.3+/-6.5; P < 0.0001), as was the oestradiol concentration (504+/-477 pg/ml versus 988+/-740 pg/ml; P < 0.03). The median dose of FSH (75 IU ampoules) used per cycle was 11 ampoules in group A and 12.5 in group B. In terms of the incidence of ovarian hyperstimulation syndrome, no differences were recorded between the two groups. The results demonstrated that r-HFSH is effective and safe in both these treatment protocols. The chronic low dose regimen was associated with a trend towards a higher rate of mono- or bifollicular development, without jeopardizing the incidence of pregnancy." ]

[ "285752", "321181", "224083", "4379365", "6754242", "4148037", "279409", "4380624", "7004469", "6365424", "359013", "4396165", "6943157", "369697", "4154819", "6088166", "4393333", "4147760", "4401615", "1890532", "4385839", "4888451", "4395021", "4400318", "7005653", "4501134", "6342787", "4383235", "271002", "6264506", "4295135", "6337712", "1055598", "6989549", "6929082", "6253112", "13270998", "4380623", "170634", "4608298", "4394685", "4153291", "6572128", "284065", "6589669", "4400046", "356989", "9017171" ]

[ "A supervised brushing trial of sodium monofluorophosphate dentifrices in a fluoridated area.", "A 3-year clinical trial of the effect on dental caries of a dentifrice containing 2% sodium monoflurophosphate.", "The relative caries-inhibiting effects of a stannous fluoride dentifrice in a silica gel base.", "Comparative study of a fluoride dentifrice containing soluble phosphate and a calcium-free abrasive: second-year report.", "Comparative unsupervised clinical trial on caries inhibition effect of monofluorophosphate and amine fluoride dentifrices after 3 years in Strasbourg, France.", "Clinical evaluation of three concentrations of sodium fluoride in dentifrices.", "A clinical trial of a calcium carbonate base dentifrice containing 0.76% sodium monofluorophosphate.", "Effectiveness of a SnF2-Ca2P2O7 dentifrice on dental caries in children whose teeth calcified in a natural fluoride area. II. Results at the end of 24 months.", "Caries prevention by dentifrices containing a combination of sodium monofluorophosphate and sodium fluoride. Report of a 3-year clinical trial.", "Caries prevention using a 1.2% sodium monofluorophosphate dentifrice in an aluminium oxide trihydrate base.", "Caries prevention by daily supervised use of a MFP gel dentifrice. Report of a 3-year clinical trial.", "Clinical testing of fluoride and non-fluoride containing dentifrices inHounslow school children.", "Effect of stannous fluoride treatments on the progression of initial lesions in approximal surfaces of permanent posterior teeth.", "A 3-year clinical trial of calcium carbonate dentifrice containing calcium glycerophosphate and sodium monofluorophosphate.", "Studies on the effect of dentifrices with low fluoride content.", "Caries inhibition of a dentifrice containing 0.78% sodium monofluorophosphate in a silica base.", "Final report on the efficacy of a stannous fluoride-calcium pyrophosphate dentifrice.", "A clinical evaluation of a stannous fluoride and a sarcosinate dentifrice.", "Clinical evaluation of an aged stannous fluoride-calcium pyrophosphate dentifrice.", "Effectiveness of fortnightly tooth brushing with amine fluorides in caries-prone subjects.", "The use of fluoride dentifrices in the control of dental caries: methodology and results of a clinical trial.", "[Three years of clinical observations with fluoridated tooth-pastes].", "The effect of a fluoride gel used for supervised toothbrushing 15 or 30 times per year.", "Clinical evaluation of neutral sodium fluoride, stannous fluoride, sodium monofluorophosphate and acidulated fluoride-phosphate denifrices.", "[Cariostatic effect of Fluocaril; controlled clinical research].", "[Effectiveness of a Na2FP03 toothpaste on caries in children].", "A four-year clinical study to determine the caries-inhibiting effect of calcium glycerophosphate and sodium fluoride in calcium carbonate base dentifrices containing sodium monofluorophosphate.", "Field test of a sodium fluoride dentifrice containing acid orthophosphate and an insoluble metaphosphate abrasive--second year report.", "Clinical testing of a mouthrinse and a dentifrice containing fluoride. A two-year supervised study in school children.", "A three-year clinical caries evaluation of the effect of a sodium fluoride-silica abrasive dentifrice.", "Cariostatic effect of a stannous fluoride-containing dentifrice on children: two-year report of a supervised toothbrushing study.", "The effects of changing caries prevalence and diagnostic criteria on clinical caries trials.", "A dentifrice containing 0.8 per cent sodium monofluorophosphatein an aluminium oxide trihydrate base. A 3-year clinical trial.", "A 3-year clinical trial into the effect of fluoride content and toothpaste abrasivity on the caries inhibitory properties of a dentifrice.", "Caries increment and gingival status during 2 years' use of chlorhexidine- and fluoride-containing dentifrices.", "Caries-inhibiting effect of a stannous fluoride silica gel dentifrice: a three-year clinical study.", "A comparison between the anticariogenic effects of dentifrices containing stannous fluoride and sodium fluoride.", "Effect of SnF2 dentrifices on caries in children: two-year clinical study of supervised brushing in children's homes.", "A clinical evaluation of a sodium fluoride dentifrice.", "Clinical trial among Scottish children of an anti-caries dentifrice containing 2 percent sodium monofluorophosphate.", "A clinical comparison of fluoride and antienzyme dentifrices.", "Caries-preventive effect of dentifrice containing 2percent sodium monofluorophosphate in a natural fluoride area in Denmark.", "Combined effects of a fluoride dentifrice and mouthrinse on the incidence of dental caries.", "The caries-preventive effect of amine fluorides and inorganic fluorides in a mouthrinse or dentifrice after 30 months of use.", "[3-year clinical tooth cream test with toothpastes of varying fluoride content: 0.8% and 1.2% sodium monofluorophosphate].", "A multiple-examiner clinical evaluation of a sodium fluoride dentifrice.", "A three-year clinical study to determine the separate and combined caries-inhibiting effects of sodium monofluorophosphate toothpaste and an acidulated phosphate-fluoride gel.", "Effect of supervised use of an alum mouthrinse on dental caries incidence in caries-susceptible children: a pilot study." ]

[ "nan", "A clinical trial of a dentifrice containing 2% sodium monofluorophosphate was carried out on 782 schoolchildren in Shropshire, England. After 3 years, a reduction of 23.8% was found in the DMFS increment obtained from clinical examination. The reduction was 38.8% using radiographs. The children were divided into three groups according to baseline DMFS. Those with a \"medium\" caries experience were found to benefit most from using the dentifrice. There was a difference in the effect on individual tooth sites; the approximal surfaces of the posterior teeth received the most benefit and the occlusal surfaces the least.", "An unsupervised toothbrushing study involving 1,339 children from 5 to 13 years of age conducted for three years compared two stannous fluoride dentifrices, one in a calcium pyrophosphate base and the other in a silica gel base, with a nonfluoride control dentifrice. The test dentifrice, stannous fluoride in a silica gel base, reduced caries to a significant extent when compared with the nonfluoride control dentifrice.The percentage of reductions ranged from 15% to 25% for whole mouth and interproximal surface indexes. There was no significant difference between the two fluoride dentifrices.", "nan", "A randomized, double blind clinical trial of the caries inhibition effects of dentifrices containing respectively monofluorophosphate and amine fluoride was performed. A third control group used a toothpaste without fluoride. A total number of 2008 schoolchildren ranging in age from 6 to 8 years and living in Strasbourg (France) participated in this study. After a baseline examination three groups were constructed with the block randomization technic. The caries inhibition effects of the three dental pastes were compared after 3 years of unsupervised use. The monofluorophosphate dentifrice showed a reduction of 7.02% for DMFT, 5.17% for DMFS and 25.26% for the df rate. The reduction of amine fluoride dentifrice caries was respectively 21.62% for DMFT, 20.94% for DMFS and 48.66% for the df rate.", "nan", "nan", "nan", "nan", "A 3-year clinical trial was carried out in France just after fluoride toothpaste was allowed to be sold on the mass market. The aim was to assess the caries preventive effect of a toothpaste containing the maximum fluoride level permitted by the EEC (1.2% SMFP). The trial started with 1318 10-12-yr-old children from a wide socioeconomic background in a typical French community. Test toothpaste was given to 659 children whereas the remaining 659 children obtained the same toothpaste without the fluoride additive. The brushing was unsupervised and performed by the children at home. Dental caries was assessed by clinical and radiographic examinations. 1061 children completed the trial. An interview carried out at the final examination identified a group of 116 uncooperative children (less than five brushings a week on average) who were not included in the statistical analysis. The following mean reductions were found: 26% for DMFT, 27% for DMFS, and 39% for DMFSU. The DMFS index for approximal, buccal-lingual and occlusal surfaces showed caries reductions of 32%, 25%, and 22%, respectively. The trial demonstrated a highly significant effectiveness of the 1.2% SMFP toothpaste in a French population.", "nan", "nan", "Bite-wing radiographs were used to determine the effect of three forms of topical SnF2 therapy on the progression of initial lesions in the approximal surfaces of permanent posterior teeth. Radiographs were taken annually over a four-year period. The subjects were schoolchildren, aged 12-14 yr, living in a low fluoride area. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, had no discernible effect on the development of the initial lesions. However, the home use of a SnF2 dentifrice did inhibit caries progression appreciably at all but one of the four time intervals in the study. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, combined with the home use of a SnF2 dentifrice, was the most effective treatment in retarding lesion development. Even without topical fluoride therapy, the rate of progression of initial approximal lesions was generally quite slow. In view of these findings, it would seem sound clinical practice to treat all initial lesions in approximal surfaces with topical fluoride therapy and delay placement of restorations until there is radiographic evidence of lesions reaching dentin.", "nan", "nan", "The purpose of this double blind clinical trial was to determine the anticaries activity of a dentifrice containing 0.78% sodium monofluorophosphate in a silica gel abrasive base compared with a placebo under conditions of supervised brushing. 1154 schoolchildren, ages 9-12, were recruited in a non-fluoridated semi-rural area of northeastern Connecticut. Subjects were stratified according to school, grade and sex, and then randomly divided into two groups. Each school day, children brushed their teeth for 1 min under supervision by project personnel. Weekend and vacation usage was ad libitum. Caries examinations and radiographic readings were performed by the same examiner (J.R.). After 12 months, the 996 subjects examined showed that the group using the test dentifrice had significantly (less than 0.05) lower DMFT (25.0%) and DMFS (19.1%) increments than the group using the placebo. After 24 months the 876 subjects examined showed that the test group continued to have significantly lower DMFT (24.5%) and DMFS (24.7%) increments than the placebo group. Surface protection after 24 months ranged from 22.1% for occlusal to 37.1% for interproximal surfaces.", "nan", "nan", "nan", "The aim of this study was to assess the caries incidence and plaque accumulation in schoolchildren at caries risk, after brushing the teeth fortnightly with gels containing 0, 0.4% F, 1.25% F as amine fluoride (AmF) or the common amine fluoride toothpaste containing 0.125% F. The study was conducted double blind over an 18-month period, and after 6 months discontinuation of brushing. Only the group that brushed with the 1.25% AmF gel showed a significant decrease in caries development compared to the group that brushed with the 0.125% AmF toothpaste. During the 6-month discontinuation period, the incidence of caries increased in all groups; the differences in caries development between all groups were not significant. Plaque indices were significantly lower in the AmF-treated groups. The highest fluoride concentration in the gel reduced the development of caries to zero, probably due to increased fluoride levels in the oral milieu of caries risk children. In order to maintain a positive effect of fluoride over an extended time period, caries-prone subjects should continue an initiated fluoride programme.", "nan", "nan", "nan", "nan", "A controlled, double-blind trial on 42 children showed that a dentrifrice containing 0,25% fluorine clearly prevented caries when used continuously for 2 years. This effects was greater than that of a similar toothpaste containing fluorine. Tolerance was excellent.", "nan", "nan", "nan", "nan", "This study was conducted to determine if the anticaries effectiveness of a 0.243% sodium fluoride-silica abrasive dentifrice is superior to a 0.4% stannous fluoride-calcium pyrophosphate dentifrice. A nonfluoride, calcium pyrophosphate abrasive placebo dentifrice was also included at one-third the sample size of the active treatment groups to estimate the level of efficacy of the sodium fluoride dentifrice. A total of 3,093 schoolchildren were randomly assigned at a ratio of 3:3:1 to the sodium fluoride dentifrice, the stannous fluoride dentifrice, or the placebo dentifrice, respectively. Caries examinations were made by the same examiner initially and after one, two, and three years of ad libitum product usage. After three years, the results showed that the group using the sodium fluoride dentifrice had significantly fewer DMF teeth and DMF surfaces increments than the group using the stannous fluoride dentifrice. The percent reductions for DMF teeth and DMF surfaces were 24.2% and 22.6%, respectively. Both groups using fluoride dentifrices also had significantly fewer DMF teeth and DMF surfaces increments than the group using the placebo dentifrice.", "nan", "nan", "nan", "The effect of reducing the abrasivity of toothpaste on dental caries was observed in a 3-year clinical trial involving 1106 11-13-year-old Berkshire schoolchildren were divided into three groups; Group 1 were allocated a low abrasivity paste containing 0.8% sodium monofluorophosphate, Group 2 a paste of conventional abrasivity also containing 0.8% sodium monofluorophosphate and Group 3 a low abrasivity non-fluoride paste. After 3 years the net DMFS increments (clinical and radiographic scores combined) were 4.22 in Group 1, 4.72 in Group 2 and 6.43 in Group 3. The differences between Groups 1 and 3 and between Groups 2 and 3 were highly significant (P less than 0.001). The mean increment in Group 1 was lower than in Group 2 but did not reach statistical significance. Reducing the abrasivity of the toothpaste had no meaningful effect on the standard of oral hygiene and prevalence of gingivitis as measured by the Gingival and Plaque Indices.", "A total of 91 schoolchildren, 13 years of age, were distributed into three groups. Three test dentifrices were used containing 0.1% NaF, 0.1% NaF and 2% chlorhexidine, and 2% chlorhexidine, respectively. The caries increment and gingival conditions over a period of 2 years were recorded. The caries data of the groups were compared and related to two reference groups in order to estimate a possible influence upon the study results by a change in caries incidence general to the area and age groups in question. There was less caries in the group using the dentifrice containing fluoride and chlorhexidine than in the two other test groups. The differences in caries increment between the groups were not statistically significant. The gingival health seemed to improve in all groups, but there were no statistically significant differences between the groups. The caries data from the reference groups indicated that the general trend towards reduced caries incidence was different from that of the study group.", "nan", "nan", "nan", "A double-blind study to determine the anticaries efficacy of a neutral pH dentifrice containing sodium fluoride and a high Beta-phase calcium pyrophosphate was conducted among elementary school children in Kansas City, Missouri. A sample of 567 children ages 8-13 were recruited and randomly assigned to test and control groups: the test group received a sodium fluoride high Beta-phase calcium pyrophosphate dentifrice, and the control group received a calcium pyrophosphate dentifrice without the active ingredient. The sodium fluoride dentifrice contained fluoride at the level of 1000 ppm. Caried examinations were conducted at initiation, after 12 months, and again after 24 months at the study's termination. All examinations (clinical and radiographic) were performed by the same investigator. At 12 months the sodium fluoride dentifrice demonstrated a caries reduction of 24.1% (DMFS). At 24 months the reduction demonstrated was 30.1% (DMFS); this reduction is significant at alpha = 0.05.", "nan", "nan", "nan", "751 14- and 15-year old children completed a 3-year, double-blind, caries preventive program. The effects of daily, supervised toothbrushing with an 0.76% sodium monofluorophosphate dentifrice, rinsing with a 0.05% sodium fluoride mouthrinse, and the combined effects of the two treatments were investigated. Both the dentifrice and mouthrinse reduced the incidence of dental caries, but their combined use at the same time had no greater effect than either used alone.", "The study groups using a dentifrice and mouthrinse both containing fluorides, a dentifrice containing stannous fluoride and a mouthrinse containing sodium fluoride, or a mouthrinse containing sodium fluoride with a placebo dentifrice had a 20.7% to 29.0% lower DMF increment than the control group after 30 months. These differences were significant. The study groups using a dentifrice containing amine fluorides and a placebo mouthrinse, a mouthrinse containing amine fluorides and a placebo dentifrice, or a dentifrice containing stannous fluoride and a placebo mouthrinse had a 13.6% to 22.4% lower DMF increment than the control group. These differences were not statistically significant. There was no significant difference in effectiveness against caries between the use of the organic or inorganic fluoride products.", "nan", "nan", "nan", "Aluminum salts have demonstrated anticaries activity in a number of laboratory and animal studies. The aim of this double-blind, pilot, clinical trial was to evaluate the effect of an alum (Al) mouthrinse on dental caries formation both by itself and in combination with an ADA-approved sodium fluoride (F) dentifrice. A total of 260 caries-prone children residing in a low-F area were preselected for the study and scored independently for caries by two experienced examiners. After using gender, age, and initial DMFT(S) scores for baseline stratification, the subjects were assigned to one of three treatment regimens: (1) placebo mouthrinse and F dentifrice, (2) Al mouthrinse and placebo dentifrice, and (3) Al mouthrinse and F dentifrice. The alum mouthrinse contained 500 ppm Al and the sodium fluoride dentifrice contained 1100 ppm F. Rinsing was supervised at school on weekdays for 30 sec/day, while the dentifrices were used ad libitum at home. Subjects were reexamined for caries and oral health after six and twelve months. Both examiners found that children who used Al mouthrinse, in conjunction with either placebo or F dentifrices, had lower caries incidence than those who used placebo mouthrinse/F dentifrice combination; but the differences were statistically significant for only one of the examiners. No evidence of deleterious effects to the oral tissues was observed. The results of this pilot clinical trial demonstrated that daily supervised use of an alum mouthrinse inhibited caries development in decay-prone children at least as effectively as a F dentifrice." ]

[ "17202945", "8651631", "9546272", "17414047", "18439948", "17942873" ]

[ "Reactivation of herpes simplex virus type 1 and varicella-zoster virus and therapeutic effects of combination therapy with prednisolone and valacyclovir in patients with Bell's palsy.", "Bell's palsy treatment with acyclovir and prednisone compared with prednisone alone: a double-blind, randomized, controlled trial.", "Idiopathic facial paralysis: a randomized, prospective, and controlled study using single-dose prednisone versus acyclovir three times daily.", "Valacyclovir and prednisolone treatment for Bell's palsy: a multicenter, randomized, placebo-controlled study.", "Acyclovir plus steroid vs steroid alone in the treatment of Bell's palsy.", "Early treatment with prednisolone or acyclovir in Bell's palsy." ]

[ "To determine whether reactivation of herpes simplex virus (HSV) type 1 or varicella-zoster virus (VZV) is the main cause of Bell's palsy and whether antiviral drugs bring about recovery from Bell's palsy.\n Randomized, multicenter, controlled study.\n One hundred fifty patients with Bell's palsy were enrolled in this study. The patients were randomly assigned to a prednisolone group or a prednisolone-valacyclovir group, in whom virologic examinations for HSV-1 and VZV were performed by simple randomization scheme in sealed envelopes. The recovery rates among various groups were analyzed using the Kaplan-Meier method and the Cox proportional hazards model.\n Reactivation of HSV-1, VZV, and both viruses was detected in 15.3%, 14.7%, and 4.0% of patients, respectively. There was no significant difference in recovery rates between the prednisolone group and the prednisolone-valacyclovir group, although recovery in the patients with HSV-1 reactivation tended to be higher in the prednisolone-valacyclovir group than in the prednisolone group. There was a significant difference in recovery among age groups and between individuals with complete and incomplete paralysis.\n Reactivation of HSV-1 or VZV was observed in 34% of the patients with Bell's palsy. The effect of combination therapy with prednisolone and valacyclovir on recovery was not significantly higher than that with prednisolone alone.", "In a double-blind study, we compared the final outcome of 99 Bell's palsy patients treated with either acyclovir-prednisone (53 patients) or placebo-prednisone (46 patients). For patients receiving acyclovir, the dosage was 2,000 mg (400 mg 5 times daily) for 10 days. Electrical tests included electroneurography and the maximal stimulation test. Univariate comparisons of outcome and electrical tests between the two groups were made with chi 2 analysis, Fisher's exact test, and t-tests. The outcome in acyclovir-prednisone-treated patients was superior to that in placebo-prednisone-treated patients. Treatment with acyclovir-prednisone was statistically more effective in returning volitional muscle motion (recovery profile of 10; p = .02) and in preventing partial nerve degeneration (p = .05) than placebo-prednisone treatment. The t-tests indicated that the recovery profile and index means were significantly better for the acyclovir-treated group (recovery profile t = 1.99, p = .051; recovery index t = 2.10, p = .040). We conclude that acyclovir-prednisone is superior to prednisone alone in treating Bell's palsy patients and suggest that herpes simplex is the probable cause of Bell's palsy.", "In a prospective, controlled, and randomized study, we compared the outcome of 101 Bell's palsy patients treated with acyclovir (54 patients) or prednisone (47 patients). The acyclovir dosage was 2400 mg (800 mg three times a day) for 10 days, and prednisone was given as a single daily dose of 1 mg/kg of body weight for 10 days and tapered to 0 over the next 6 days. Minimum follow-up was 3 months in all patients. Patients in the prednisone group had better clinical recovery than those treated with acyclovir. Less degree of neural degeneration was observed in the prednisone group compared with acyclovir patients. The incidence of sequelae was the same in both groups. According to these results, in a 10-day treatment cycle acyclovir given 800 mg three times is not as useful as prednisone given 1 mg/kg of body weight once a day in patients with idiopathic facial nerve paralysis.", "To investigate the effects of valacyclovir and prednisolone in comparison with those of placebo and prednisolone for the treatment of Bell's palsy, excluding zoster sine herpete.\n Prospective, multicenter, randomized placebo-controlled study.\n Six academic tertiary referral centers.\n Ultimately, 221 patients with Bell's palsy who were treated within 7 days of the onset. Serological and polymerase chain reaction examinations were performed to distinguish Bell's palsy from zoster sine herpete.\n The patients were treated with either valacyclovir (dosage, 1,000 mg/d for 5 days) plus prednisolone (VP [n = 114]) or placebo plus prednisolone (PP [n = 107]) administered orally.\n Recovery from the palsy was defined as a score higher than 36 using Yanagihara 40-point scoring system without facial contracture or synkinesis. The patients were followed up until complete recovery occurred or for more than 6 months in cases with a poor prognosis.\n The overall rate of patient recovery among those treated with VP (96.5%) was significantly better (p < 0.05) than the rate among those treated with PP (89.7%). The rate of patient recovery was also analyzed by classifying the initial severity of facial palsy. In cases of complete or severe palsy, the rates of patients treated with VP and PP who recovered were 95.7% (n = 92) and 86.6% (n = 82), respectively; the recovery rate for treatment with VP was significantly better than that with PP (p < 0.05).\n The valacyclovir and prednisolone therapy was more effective in treating Bell's palsy, excluding zoster sine herpete, than the conventional prednisolone therapy. To our knowledge, this is the first controlled study of an antiviral agent in the treatment of a sufficient number of Bell's palsy cases based on an etiologic background.", "The pathogenetic mechanism of Bell's palsy is thought to involve herpes simplex virus reactivation within the geniculate ganglion, followed by inflammation and entrapment of the nerve at the meatal foramen. We therefore compared the therapeutic effect of acyclovir plus steroid vs steroid alone, in combination with physical therapy, in patients with Bell's palsy.\n In a double-blind, randomized, prospective trial, 91 patients were randomized to treatment with acyclovir and prednisone (44 patients) or prednisone alone (47 patients). All patients underwent physical therapy. The follow-up period was greater than 6 months or encompassed the period of complete recovery from paralysis. House-Brackmann grade was evaluated 2 and 6 months after onset, with complete and satisfactory recovery defined as House-Brackmann grades I and II, respectively.\n The overall recovery rate of patients treated with steroid and acyclovir (93.1%) was greater than that of patients treated with steroid alone (85.1%), but the difference was not statistically significant.\n The benefit of acyclovir in Bell's palsy has not been definitively established.", "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." ]

[ "10990114" ]

[ "Heparin-bonded central venous lines reduce thrombotic and infective complications in critically ill children." ]

[ "To determine whether heparin bonding reduces the incidence of catheter-related thrombosis and infection in critically ill children.\n A prospective double-blind randomized controlled study.\n A tertiary paediatric intensive care unit.\n Two hundred and nine patients, 123 males and 86 females, aged 0-16 years, admitted to the intensive care unit and needing a central venous line (CVL), were randomized to receive either a heparin-bonded (HB, n = 102) or a non-heparin-bonded line (NHB, n = 107). Nine patients were excluded owing to incomplete data.\n HB or NHB CVL.\n Blood cultures were carried out on insertion of the line and every 3 days thereafter. Ultrasound was performed within the first 3 days and every 3 days thereafter. On removal the line was sent for culture. Results: The two groups were comparable for age, sex, severity of illness and length of time that the catheter was in situ. Proportional hazards modelling showed that heparin bonding was associated with a significant reduction in infections (hazard ratio 0.11, P < 0.00005). The incidence of infection was 4% and 33% in HB and NHB CVLs, respectively (4/97 vs. 34/103, P < 0.0005). The incidence of thrombosis was 0% and 8% in HB and NHB CVLs, respectively (0/97 vs. 8/103, P = 0.006). The number of HB CVLs which would need to be used to avoid one episode of infection or thrombosis was 3 and 13, respectively.\n Our study shows a significant reduction in the incidence of infection and thrombosis associated with the use of HB CVLs." ]

[ "7492381", "8918495", "12972521", "19014494", "17317205", "15718314", "8638531", "7541448" ]

[ "Effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on hematologic toxicity induced by high-dose chemotherapy in patients with metastatic breast cancer.", "Randomized double-blind prospective trial to evaluate the effects of sargramostim versus placebo in a moderate-dose fluorouracil, doxorubicin, and cyclophosphamide adjuvant chemotherapy program for stage II and III breast cancer.", "Addition of either lonidamine or granulocyte colony-stimulating factor does not improve survival in early breast cancer patients treated with high-dose epirubicin and cyclophosphamide.", "XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy.", "Pegfilgrastim supports delivery of FEC-100 chemotherapy in elderly patients with high risk breast cancer: a randomized phase 2 trial.", "First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study.", "Prophylactic filgrastim (G-CSF) during mitomycin-C, mitoxantrone, and methotrexate (MMM) treatment for metastatic breast cancer. A randomized study.", "Lenograstim prevents morbidity from intensive induction chemotherapy in the treatment of inflammatory breast cancer." ]

[ "Twenty patients with recurrent metastatic breast cancer treated with high-dose myelosuppressive antineoplastic drugs (cyclophosphamide 2.5 g/m2 or epirubicin 130 mg/m2, both every 3 weeks) as first or second line chemotherapy were randomized in a prospective study to GM-CSF 5 micrograms/kg per day (n = 11) or control (n = 9). Significant reduction in granulocyte nadir duration (2 days with GM-CSF vs. 7 days) and severity (0.4 x 10(9)/l with GM-CSF vs. 0.2 x 10(9)/l) was found. No difference in frequency of neutropenic fever or antibiotic use could be observed. Even though the patients treated with GM-CSF at random were more heavily pretreated with chemotherapy, there was a surprisingly higher response rate in these patients as compared to the control-arm, namely 64% vs. 28.5%. However, this difference was not statistically significant. No severe side-effects were seen, but presumably due to GM-CSF one patient developed an allergic type 1 reaction and one patient a possible pericardial exudation. Both were fully reversible after cessation of the cytokine treatment.", "To determine the effects of sargramostim (recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) on the incidence, duration, and complications of myelosuppression after moderate-dose fluorouracil, doxorubicin, cyclophosphamide (FAC) adjuvant chemotherapy in patients with node-positive breast cancer.\n In this randomized, double-blind, placebo-controlled study, 142 women with stage II and III breast cancer were to receive four 21-day cycles of chemotherapy that consisted of fluorouracil 600 mg/ m2 intravenously (IV), doxorubicin 60 mg/m2 IV, and cyclophosphamide 750 mg/m2 IV on day 1, followed by placebo or GM-CSF 250 micrograms/m2/d daily subcutaneously (SC) on days 3 through 15. All patients received prophylactic ciprofloxacin by mouth when the absolute neutrophil count (ANC) was less than 1,000/microL.\n Eighty-six percent of GM-CSF patients (n = 62) and 96% of placebo patients (n = 69) completed four assessable cycles of treatment on study. Overall, the median duration of severe neutropenia (ANC < 500/microL) was 2.8 days with GM-CSF and 6.8 days with placebo (P < .001); the duration of ANC less than 1,000/microL was 6.0 versus 9.1 days, respectively (P < .001). Hospitalizations for febrile neutropenia were uncommon in either group: GM-CSF, six; placebo, eight. The only other difference in hematologic toxicity was grade 3/4 thrombocytopenia observed with greater frequency in GM-CSF patients than placebo patients in cycles 3 and 4. GM-CSF increased mean the FAC dose-intensity among patients who completed two or more cycles (P < .001). GM-CSF was generally well tolerated and associated with more injection-site reactions, but less mucositis than placebo. There were no deaths on study.\n GM-CSF significantly enhanced ANC recovery after FAC chemotherapy; it decreased the incidence and duration of associated neutropenia and moderately increased the dose-intensity of adjuvant chemotherapy. Whether these effects will ultimately translate into improved long-term outcome remains to be determined.", "Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity.\n From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients).\n Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non-G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non-G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively).\n EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.", "Recombinant granulocyte colony-stimulating factors (G-CSFs) such as Filgrastim are used to treat chemotherapy-induced neutropenia. We investigated a new G-CSF, XM02, and compared it to Neupogen after myelotoxic chemotherapy in breast cancer (BC) patients.\n A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were randomised to treatment with daily injections (subcutaneous 5 microg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of XM02 (n = 140), Neupogen (n = 136) or placebo (n = 72). The primary endpoint was the duration of severe neutropenia (DSN) in cycle 1.\n The mean DSN in cycle 1 was 1.1, 1.1, and 3.9 days in the XM02, Neupogen, and placebo group, respectively. Superiority of XM02 over placebo and equivalence of XM02 with Neupogen could be demonstrated. Toxicities were similar between XM02 and Neupogen.\n XM02 was superior to placebo and equivalent to Neupogen in reducing DSN after myelotoxic chemotherapy.", "This randomized phase 2 study explored the feasibility of delivering four to six cycles of the dose-intensified regimen FEC-100 (5-fluorouracil, epirubicin, and cyclophosphamide) to elderly patients with stage II-III breast cancer, using pegfilgrastim for neutrophil support. Sixty patients aged 65-77 years received single 6mg doses of pegfilgrastim on day 2 of FEC-100, either as primary prophylaxis (all cycles: PP), or as secondary prophylaxis (all cycles following a neutropenic event: SP). Neutropenic events (a composite endpoint that included grade 3 neutropenia+fever, grade 4 neutropenia, infectious complication requiring systemic anti-infectives and chemotherapy dose delay/reduction) occurred in 24/30 (80%) of the PP and 21/29 (72%) of the SP group in the first cycle. Most patients received all chemotherapy cycles at full dose on schedule (26/30 [87%] PP; 20/29 [69%] SP). These data indicate that delivery of FEC-100 is feasible with pegfilgrastim support in elderly breast cancer patients.", "We evaluated the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia associated with docetaxel in breast cancer patients.\n Patients were randomly assigned to either placebo or pegfilgrastim 6 mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m(2) docetaxel. The primary end point was the percentage of patients developing febrile neutropenia (defined as body temperature >/= 38.2 degrees C and neutrophil count < 0.5 x 10(9)/L on the same day of the fever or the day after). Secondary end points were incidence of hospitalizations associated with a diagnosis of febrile neutropenia, intravenous (IV) anti-infectives required for febrile neutropenia, and the ability to maintain planned chemotherapy dose on time. Patients with febrile neutropenia were converted to open-label pegfilgrastim in subsequent cycles.\n Nine hundred twenty-eight patients received placebo (n = 465) or pegfilgrastim (n = 463). Patients receiving pegfilgrastim, compared with patients receiving placebo, had a lower incidence of febrile neutropenia (1% v 17%, respectively; P < .001), febrile neutropenia-related hospitalization (1% v 14%, respectively; P < .001), and use of IV anti-infectives (2% v 10%, respectively; P < .001). The percentage of patients receiving the planned dose on time was similar between patients receiving pegfilgrastim and patients who initially received placebo (80% and 78%, respectively), as would be expected of the study design. Pegfilgrastim was generally well tolerated and safe, and the adverse events reported were typical of this patient population.\n First and subsequent cycle use of pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly reduced febrile neutropenia, febrile neutropenia-related hospitalizations, and IV anti-infective use.", "Patients with metastatic breast cancer were randomly assigned to receive as second-line chemotherapy either MMM (mitomycin 8 mg/m2 day 1; mitoxantrone 8 mg/m2 days 1 and 22; methotrexate 35 mg/m2 days 1 and 22) alone or in combination with filgrastim (5 micrograms/kg s.c. days 4-17, 24-37). The courses were repeated every 42 days for a maximum of six courses. Thirty-one patients are evaluable for safety and efficacy. The 16 patients in the filgrastim arm received a total of 42 cycles compared with 34 cycles in the 15 control patients. Tumor responses were few in both patient groups (one partial response in the filgrastim group and two partial responses in control group). Nevertheless, a difference in survival was seen (filgrastim median 10.7 months, control median 6.5 months; p = 0.02 log rank). The treatment was well tolerated. Doses were reduced six times in the filgrastim arm and eleven times in the control arm. Grade IV neutropenia was seen in four patients in the filgrastim arm and in twelve patients in the control arm. The observed survival benefit needs to be confirmed in a larger patient group.", "To compare the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) versus its inert vehicle in patients with unilateral nonmetastatic inflammatory breast cancer treated with fluorouracil, epirubicin, and cyclophosphamide high-dose (FEC-HD) neoadjuvant chemotherapy.\n One hundred twenty patients have been enrolled by nine French centers in this double-blind, parallel-group, vehicle-controlled study to compare at each cycle subcutaneous lenograstim (5 micrograms/kg/d) with placebo given from day 6 to day 15 after the induction chemotherapy (day 1 to day 4, fluorouracil 750 mg/m2 continuous intravenous [IV] infusion; day 2 to day 4, epirubicin 35 mg/m2 and cyclophosphamide 400 mg/m2 both IV push). Four cycles were planned every 3 weeks before locoregional treatment. Patients with febrile neutropenia remained blinded for the subsequent cycles.\n Lenograstim significantly reduced the duration of neutropenia at less than 0.5 x 10(9)/L and less than 1 x 10(9)/L to a median duration of 2 and 3 days, respectively, as compared with 5 and 7 days in the placebo group. This translated into a statistically significant reduced incidence of microbiologically documented infections, and a decreased need for rehospitalizations for infectious events and antibiotic use. Clinical objective tumor response rate observed after four cycles was 89.6% and 93%, respectively, in the placebo and treated groups. Mild transient bone and injection-site pain, myelemia, and hyperleukocytosis were the most frequently reported adverse events associated with lenograstim.\n Lenograstim is safe and effective to reduce morbidity associated with FEC-HD neoadjuvant chemotherapy in inflammatory breast cancer. Response rate is not affected." ]

[ "11730179", "10491451", "9230238", "12735675", "12468439", "10821721", "9109702", "16440533", "12847482", "10094216", "8222787", "11140431", "10211538", "15065610", "10329812", "8627205", "8707781", "12765916", "12735661", "7664857", "8760776", "7930300", "9679845", "9949318", "9663359", "12475834", "9544904", "10200011", "10678614", "10936116", "8879892", "9576141", "10390394", "16393726", "7582278" ]

[ "Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients.", "Effects of inhaled fluticasone and oral prednisolone on clinical and inflammatory parameters in patients with asthma.", "Short-term knemometry and urine cortisol excretion in children treated with fluticasone propionate and budesonide: a dose response study.", "Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma.", "Vascular component of airway remodeling in asthma is reduced by high dose of fluticasone.", "Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma.", "Comparative efficacy and safety of twice daily fluticasone propionate powder versus placebo in the treatment of moderate asthma.", "Fluticasone propionate hydrofluoroalkane inhalation aerosol in patients receiving inhaled corticosteroids.", "Effect of inhaled fluticasone with and without salmeterol on airway inflammation in asthma.", "Inhaled salmeterol and fluticasone: a study comparing monotherapy and combination therapy in asthma.", "A dose-ranging study of fluticasone propionate in adult patients with moderate asthma. International Study Group.", "Pharmacokinetics of fluticasone propionate inhaled via the Diskhaler and Diskus powder devices in patients with mild-to-moderate asthma.", "Effects of the inhaled corticosteroids fluticasone propionate, triamcinolone acetonide, and flunisolide and oral prednisone on the hypothalamic-pituitary-adrenal axis in adult patients with asthma.", "Potential effects of fluticasone propionate on bone mineral density in patients with asthma: a 2-year randomized, double-blind, placebo-controlled trial.", "A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma.", "Fluticasone propionate aerosol: efficacy in patients with mild to moderate asthma. Fluticasone Propionate Asthma Study Group.", "A 12-week dose-ranging study of fluticasone propionate powder in the treatment of asthma.", "Fluticasone propionate in asthma: a long term dose comparison study.", "Fifty microg b.i.d. of inhaled fluticasone propionate (FP) are effective in stable asthmatics previously treated with a higher dose of FP.", "High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate, 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. International Study Group.", "Fluticasone propionate compared with theophylline for mild-to-moderate asthma.", "Fluticasone propionate aerosol for the treatment of adults with mild to moderate asthma. The Fluticasone Propionate Asthma Study Group.", "Inhaled fluticasone propionate delivered by means of two different multidose powder inhalers is effective and safe in a large pediatric population with persistent asthma.", "Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma.", "Fluticasone propionate 50 micrograms BID versus 100 micrograms BID in the treatment of children with persistent asthma. Fluticasone Propionate Study Group.", "Effects of varying doses of fluticasone propionate on the physiology and bronchial wall immunopathology in mild-to-moderate asthma.", "Growth in asthmatic children treated with fluticasone propionate. Fluticasone Propionate Asthma Study Group.", "Effects of fluticasone propionate, triamcinolone acetonide, prednisone, and placebo on the hypothalamic-pituitary-adrenal axis.", "Low- and high-dose fluticasone propionate in asthma; effects during and after treatment.", "A dose-ranging study of fluticasone propionate administered once daily via multidose powder inhaler to patients with moderate asthma.", "Effectiveness of fluticasone propionate in patients with moderate asthma: a dose-ranging study.", "Dose-related response to inhaled fluticasone propionate in patients with methacholine-induced bronchial hyperresponsiveness: a double-blind, placebo-controlled study.", "Systemic effects of inhaled fluticasone propionate and budesonide in adult patients with asthma.", "Fluticasone propionate HFA-134a pressurized metered-dose inhaler in adolescents and adults with moderate to severe asthma.", "Fluticasone propionate reduces oral prednisone use while it improves asthma control and quality of life." ]

[ "Suppression of the hypothalamic-pituitary-adrenal (HPA) axis, a potential systemic effect of inhaled corticosteroid therapy, can be quantified by monitoring serum, urinary, and salivary cortisol levels.\n 1) Compare the effects on HPA axis of the inhaled corticosteroids flunisolide and fluticasone propionate versus placebo and oral prednisone. 2) Estimate dose-potency ratio for HPA-axis suppression.\n Multicenter, randomized, placebo-controlled, open-label, 21-day trial. Active regimens were flunisolide 500 and 1,000 microg, twice daily; fluticasone propionate 110, 220, 330, and 440 microg, twice daily; and prednisone, 7.5 mg daily. Enrolled patients were nonsmokers, 18 to 50 years of age, with persistent mild-to-moderate asthma and had not used oral, nasal, or inhaled corticosteroids for 6 months before study. Main outcome measures were area under serum cortisol concentration curve for 22 hours (AUC(0-22h)); 24-hour urinary cortisol level; and 8 AM salivary cortisol level.\n One hundred fifty-three patients were randomly assigned to active treatment or placebo; 125 patients completed the study and were at least 80% compliant with their regimens. Both fluticasone propionate and flunisolide caused dose-dependent suppression of HPA axis, which was statistically greater for fluticasone propionate (P = 0.0003). Dose-potency ratio showed 4.4 times more serum-cortisol suppression/microgram increase in dose with fluticasone propionate than with flunisolide. Diurnal pattern of serum cortisol suppression was persistent with fluticasone propionate and \"remitting\" with flunisolide. Salivary and urinary cortisol data were qualitatively similar to serum cortisol results.\n Fluticasone caused significantly more suppression of HPA axis than flunisolide. Flunisolide may provide a safe option for patients with asthma requiring long-term inhaled corticosteroid therapy.", "Guidelines state that oral and inhaled corticosteroids are the cornerstone of asthma treatment. The effect of both types of treatment can be assessed by measuring lung and systemic parameters. Treatment for two weeks with either oral prednisolone (30 mg/day), high dose fluticasone propionate (2000 microg/day, FP2000), or lower dose FP (500 microg/day, FP500), both given by a dry powder inhaler, were compared.\n One hundred and twenty patients with asthma were treated for two weeks in a double blind parallel group design. Lung function, asthma symptoms, airway hyperresponsiveness (PC(20) methacholine and adenosine-5'-monophosphate), sputum eosinophil and eosinophilic cationic protein (ECP) levels were measured as lung parameters. In addition, morning serum blood cortisol, blood eosinophil, and serum ECP levels were measured as systemic parameters.\n PC(20) methacholine and adenosine-5'-monophosphate showed significantly greater improvement with FP2000 (1.99 and 4.04 doubling concentrations (DC), respectively) than prednisolone (0.90 DC, p = 0.02; 2.15 DC, p = 0. 05) and marginally more than with FP500 (1.69 and 3.54 DC). Changes in sputum eosinophil and ECP concentrations showed similar trends; the decrease in ECP was significantly greater with FP2000 than with FP500. In contrast, the systemic parameters of steroid activity (cortisol, peripheral blood eosinophils, and serum ECP) decreased to a similar extent with FP2000 and prednisolone but significantly less with FP500.\n Oral prednisolone (30 mg/day) was inferior to FP2000 in improving airway hyperresponsiveness to both methacholine and AMP, with similar trends in forced expiratory volume in one second (FEV(1)), sputum eosinophil and ECP concentrations. Systemic effects were similar with prednisolone and FP2000 and less with FP500.", "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 study was designed to determine whether the benefit of adding salmeterol was superior to doubling the dose of fluticasone propionate (FP) over 6 months, compared to a control group who remained on a lower dose of FP. The multi-centre, double-blind, parallel group study involved 496 symptomatic asthmatic patients with a history of exacerbations on 500-800 micrograms (microg) inhaled corticosteroids (ICS) twice daily (b.d.) in a broadly representative group of 100 hospitals and general practices in six countries. Two doses of FP--250 microg b.d. (FP250) or 500 microg b.d. (FP500)--were compared with the lower dose of FP plus a long-acting beta2-agonist, salmeterol 50 microg b.d. (SM/FP250). Patients symptomatic on the run-in dose of FP250 alone formed the control group in the treatment period. Over 6 months, SM/FP250 significantly improved mean morning peak expiratory flow rates (amPEF) by 42.1 l/min, more than twice the improvement achieved with either dose of FP alone. SM/FP250 also resulted in more symptom-free days and nights (P < 0.002) and days and nights with no relief medication (P < 0.001). The number of severe exacerbations was low: 3, 6 and 8% in the SM/FP250, low- and high-dose FP groups, respectively. This study confirms that adding salmeterol to low-dose inhaled FP offers greater improvements than either maintaining or doubling the dose of FP. Significant benefit was gained from adding salmeterol in a group of patients who appeared to have been at the top of their steroid dose-response curve receiving FP250. There was no evidence of tolerance and a low incidence of exacerbations in all treatment groups.", "We conducted a randomized, double-blind, parallel-group study to assess the effect of 6 weeks treatment with low-dose (100 microg twice a day) or high-dose (500 microg twice a day) inhaled fluticasone propionate (FP) on the vascular component of airway remodeling in 30 patients with mild to moderate asthma. We also studied the effect on the inflammatory cells and the basement membrane thickness, and we compared findings from bronchial biopsies taken in patients with asthma with those in eight control subjects. Bronchial responsiveness to methacholine and asthma symptom score were measured before and after treatments. Eight patients in the low-dose FP group and eight patients in high-dose FP group completed the study. At baseline, patients with asthma showed an increase in the number of vessels and in vascular area as compared with control subjects. In the subjects with asthma, number of vessels correlated with vascular area (p < 0.01) and with number of mast cells (p < 0.01). Bronchial responsiveness to methacholine, asthma symptom score, and inflammatory cells decreased significantly after both low- and high-dose FP (p < 0.05). However, the number of vessels, the vascular area, and the basement membrane thickness decreased only after high-dose FP (p < 0.05). In conclusion, this study shows that in patients with mild to moderate asthma, high dose of inhaled FP given over 6 weeks can significantly affect airway remodeling by reducing both submucosal vascularity and basement membrane thickness.", "When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 microg bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV(1)) >/=70% predicted; EIB >/=20% fall in FEV(1) from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were re-randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV(1) from baseline) and methacholine challenge using a dosimetric technique (expressed as PD(20)) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV(1) being reduced from 34.1% to 9.9% for 100 microg FP bid, and from 35.9% to 7.6% for 250 microg FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD(20) methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 microg FP bid, 1.6 dose steps; 250 microg FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment.\n Copyright 2000 Wiley-Liss, Inc.", "Fluticasone propionate, an inhaled corticosteroid with negligible systemic bioavailability via the oral route, is efficacious in the treatment of asthma when administered via metered-dose inhaler.\n To evaluate the efficacy and safety of inhaled fluticasone propionate powder in patients with moderate asthma previously treated with an inhaled corticosteroid.\n This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 342 adolescent and adult patients with moderate asthma [forced expiratory volume in 1 second (FEV1) between 50% and 80% of predicted] treated previously by beclomethasone dipropionate or triamcinolone acetonide. Patients received fluticasone propionate powder 50 micrograms, 100 micrograms, 250 micrograms, or placebo via a breath-actuated inhalation device, the Diskhaler, twice daily for 12 weeks.\n Patients in the fluticasone propionate groups experienced a mean increase from baseline to endpoint in FEV1 ranging from 0.43 L to 0.47 L. Patients in the placebo group experienced a mean decrease from baseline of 0.22 L (P < .001). The probability of patients remaining in the study over time without developing signs of exacerbating asthma was significantly greater in the fluticasone propionate groups than in the placebo group (P = .001). Asthma symptom scores, supplemental rescue albuterol use, and number of nighttime awakenings due to asthma requiring treatment also improved significantly with all fluticasone propionate treatment regimens compared with placebo (P < .001). There were no statistically significant differences at endpoint among the three fluticasone propionate groups. No serious drug-related adverse events occurred.\n Fluticasone propionate powder (50, 100, and 250 micrograms) was well-tolerated and significantly improved lung function in patients with moderate asthma.", "Inhaled corticosteroids (ICSs) delivered by metered-dose inhalers that contain chlorofluorocarbon propellants are being discontinued because of the harmful effects of chlorofluorocarbon on the ozone layer. Therefore, some metered-dose inhaler products are being reformulated with \"ozone-friendly\" hydrofluoroalkane propellants.\n To evaluate treatment with fluticasone propionate hydrofluoroalkane inhalation aerosol, 88, 220, and 440 microg twice daily, vs placebo in patients with asthma receiving an ICS.\n Randomized, double-blind, parallel-group, 12-week study.\n Mean morning predose percent predicted forced expiratory volume in 1 second increased by 2.2%, 3.2%, and 4.6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively, compared with an 8.3% decrease for placebo (P < .001 vs placebo for all groups). Secondary pulmonary function end points and asthma symptoms showed similar improvements compared with placebo. Discontinuation from the study due to lack of efficacy was 50% in the placebo group and 11%, 10%, and 6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively. At week 12, the probability of remaining in the study was 0.89, 0.90, and 0.94 for the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively, vs 0.45 for the placebo group (P < .001 for all). Changes in 24-hour urinary cortisol excretion rates were similar among treatment groups.\n Fluticasone propionate hydrofluoroalkane, previously shown to be a clinically suitable alternative to fluticasone propionate chlorofluorocarbon, was effective and well tolerated. The ability to switch from fluticasone propionate chlorofluorocarbon and other chlorofluorocarbon-containing ICSs to fluticasone propionate hydrofluoroalkane without sacrificing asthma control or tolerability will facilitate a smooth transition to this nonchlorofluorocarbon-containing medicinal.", "The clinical benefit of combining long-acting beta(2)-agonists with inhaled corticosteroids rather than doubling the dose of corticosteroid has been well-documented. However, there are concerns that this might result in a masking of underlying airway inflammation.\n The aim of this study was to test the hypothesis that the addition of the long-acting beta(2)-agonist salmeterol (SALM) to a low dose of the inhaled corticosteroid fluticasone propionate (FP) has a steroid-sparing effect and does not result in a worsening of bronchial inflammation compared to doubling the dose of inhaled corticosteroid.\n Fifty-six asthmatic subjects, previously not well-controlled on inhaled corticosteroids, were randomized to receive 3 months of treatment with inhaled FP 500 microg twice a day (FP 1000) or FP 200 microg twice a day plus SALM 50 microg twice a day (FP 400 + SALM). Fluticasone propionate 200 microg twice a day served as the control (FP400). Bronchial mucosal biopsy specimens, bronchial washings (BW), and bronchoalveolar lavage were obtained before and after treatment. The primary end points for the study were submucosal mast cell and eosinophil counts.\n There was a significant improvement in FEV(1) in the FP400 + SALM group compared to both the FP400 and FP1000 groups. This was accompanied by a significant improvement in peak expiratory flow in the FP400 + SALM group in both the morning and evening compared to the FP1000 group. There were no significant between treatment differences in the change in the number of submucosal mast cells or eosinophils. However, in the FP400 + SALM group there was a significant decrease in submucosal mast cells after 12 weeks of treatment. The addition of SALM to FP was not associated with any increases in airway inflammation in the biopsy specimens, bronchoalveolar lavage, or bronchial washings.\n These findings confirm that addition of SALM to FP has clinical benefits but does not mask or exacerbate airway inflammation and suggest that long-acting beta(2)-adrenoceptor agonists might influence mast cell numbers.", "The current stepwise approach to pharmacotherapy in the treatment of asthma includes the initiation of an inhaled corticosteroid with the addition of a long-acting inhaled bronchodilator if low dose inhaled corticosteroid fails to control asthma symptoms.\n To determine whether initiation of salmeterol and fluticasone propionate treatment together improves asthma control greater than initiation of monotherapy with the individual agents alone with no additional safety risk in patients with asthma who had not previously been treated with inhaled corticosteroids.\n A total of 136 male and female patients at least 12 years of age with asthma [forced expiratory volume in 1 second (FEV) between 50% and 80% of predicted] were randomized to twice daily salmeterol 42 microg, fluticasone propionate 88 microg, fluticasone propionate 220 microg, salmeterol 42 microg plus fluticasone propionate 88 microg, salmeterol 42 microg plus fluticasone propionate 220 microg, or placebo for 4 weeks.\n Patients treated with salmeterol combined with fluticasone propionate had improvements over baseline in FEV at endpoint that were at least twice as great (0.6 to 0.7 L) as improvements in patients treated with salmeterol (0.3 L) or fluticasone propionate alone (0.3 L) (P < .05). Patient-rated data (peak expiratory flow, asthma symptom scores, percent of days with no asthma symptoms) confirmed greater (P < .05) mean change from baseline improvements after combined treatment compared with fluticasone propionate alone. No clinically significant differences were noted between treatment groups in any safety measurement.\n Initiation of maintenance therapy with salmeterol and fluticasone propionate in patients with asthma treated with short-acting beta2-agonists alone provides greater improvements in pulmonary function and symptom control than initiation of maintenance therapy with fluticasone propionate alone.", "In this 4-week, multicenter, double-blind, randomized, parallel group study, the dose-effect relationship of four doses of inhaled fluticasone propionate (50, 100, 200, and 400 micrograms twice daily) was investigated and compared with beclomethasone dipropionate, 200 micrograms twice daily. A total of 672 patients with moderate asthma currently receiving 1,000 micrograms/d or less of an inhaled steroid were recruited. The study demonstrated a significant dose-related improvement in lung function with fluticasone propionate. Linear dose-related increases were observed in morning (increase per doubling dose was 4.3 L/min; 95 percent confidence interval [CI], 1.8, 6.8 L/min; p = 0.001) and evening peak expiratory flow rate (PEFR) (increase per doubling dose was 3.0 L/min; 95 percent CI, 0.5, 5.5 L/min; p = 0.017), clinic lung function (at 4 weeks, increase in percent predicted PEFR per doubling dose = 1.1 percent; 95 percent CI, 0.2, 2.1 percent; p = 0.022; increase in percent predicted FEV1 per doubling dose = 1.1 percent; 95 percent CI, 0.3, 1.9 percent; p = 0.10:increase in percent predicted FVC per doubling dose = 1.3 percent, 95 percent CI, 0.5, 2.1 percent; p = 0.001), and the percentage of symptom-free days over days 1 to 14 of treatment (increase per doubling dose = 1.9, 95 percent CI, 0.0, 3.9; p = 0.048). There was also a dose-related reduction in extra bronchodilator usage (days 1 to 14 p = 0.002; days 15 to 28 p = 0.01). In addition, there was a significant decrease in diurnal variation with increasing doses of fluticasone propionate (decrease per doubling dose = 2.0 L/min, 95 percent CI, 0.4; p = 0.024). The number of asthma exacerbations was also reduced as the dose of fluticasone propionate increased. Fluticasone propionate was well tolerated, adverse events were few, and there was a similar incidence in all groups. Furthermore, there was no evidence of any hypothalamic pituitary adrenal axis suppression. The data from the study were consistent with other clinical studies that have shown fluticasone propionate to be more potent than beclomethasone dipropionate in terms of improvement in lung function. In conclusion, this study provided evidence of a dose-related improvement in asthma control for fluticasone propionate in the dose range 100 to 800 micrograms daily, in patients with moderate asthma.", "The aim of these studies was to compare the pharmacokinetics of inhaled fluticasone propionate (FP) after repeated administration via the Diskus or Diskhaler dry powder inhalers (DPIs) to patients with mild-to-moderate asthma.\n Both studies evaluated the pharmacokinetics of inhaled administration of FP via a DPI to patients with mild-to-moderate asthma, according to a randomised, double-blind, placebo-controlled design. In the first study, FP 100 microg or 500 microg was administered twice daily via the Diskhaler for 6 weeks and, in the second, FP 500 microg was administered via the Diskus or Diskhaler for 12 weeks.\n In the first study, plasma FP concentrations could be detected consistently only with the higher dose; the lower dose produced concentrations close to or below the 0.025 microg/L quantification limit of the radioimmunoassay used. From detailed analysis of a subgroup of patients receiving the 500 microg dosage, steady-state plasma FP concentrations were attained within one week of commencing treatment. After 4 weeks, the maximum plasma FP concentration (Cmax) in this subgroup was 0.096 microg/L [95% confidence interval (CI) 0.066-0.141] and the area under the plasma FP concentration-time curve up to the last quantifiable concentration (AUClast) was 0.491 microg/L x h (95% CI: 0.256-0.940). The steady-state to single dose accumulation ratio for FP after twice-daily administration varied between patients: a ratio of approximately 1.7 was recorded after comparison of Cmax at week 4 and day 1. In the second study, the point estimate of the Diskus to Diskhaler ratio for Cmax in all patients was 0.91 (90% CI: 0.76-1.10) after 4 weeks' treatment. From a detailed analysis of a subgroup of patients, the corresponding ratio for AUClast at the same time point was 1.15 (90% CI: 0.69-1.94), indicating no significant difference in systemic exposure to FP between the 2 devices. Steady-state kinetics were achieved by week 1: the point estimate ratios of Cmax and AUClast at week 4 compared with week 1 were 0.88 (90% CI: 0.66-1.16) and 0.95 (90% CI: 0.66-1.36), respectively. Administration of FP via either DPI had no effect on plasma cortisol levels over the 12-hour postdose period.\n In patients with asthma receiving repeated inhaled doses of FP, the systemic exposure (AUC) after inhalation from the Diskus was similar to that from the Diskhaler, with no difference between the DPIs in the effects on cortisol suppression. The 2 DPIs therefore have very similar pharmacokinetic profiles.", "Two multicenter, randomized, double-masked, placebo-controlled, parallel-group studies were conducted in adult patients with mild-to-moderate persistent asthma to assess the effects of 4 weeks of treatment with inhaled corticosteroids on hypothalamic-pituitary-adrenal (HPA) axis function. The first study compared fluticasone propionate 100 and 500 microg twice daily, triamcinolone acetonide 300 and 500 microg twice daily, oral prednisone 10 mg every morning, and placebo. The second study compared fluticasone propionate 100 and 250 microg twice daily, flunisolide 500 microg twice daily, and placebo. Therapeutic doses of fluticasone propionate, triamcinolone acetonide, and flunisolide were found to be comparable to each other and to placebo in their lack of adrenal suppressive effects, based on mean plasma cortisol responses to 6-hour cosyntropin infusion. Prednisone produced significantly greater suppression of HPA-axis function than did any of the inhaled corticosteroids or placebo (P<0.001). Mean reductions from baseline in 8-hour area under the plasma concentration-time curve (AUC) and 8-hour peak plasma cortisol concentrations and the mean percentage of change from baseline in 8-hour AUC were significantly greater after treatment with triamcinolone acetonide 500 microg twice daily compared with placebo (P< or =0.042). These findings indicate that fluticasone propionate has no greater systemic effect than either triamcinolone acetonide or flunisolide at doses appropriate for patients with mild-to-moderate persistent asthma.", "To evaluate the effects of treatment with fluticasone propionate vs placebo on bone, hypothalamic-pituitary-adrenal (HPA) axis function, and the eyes in patients with asthma.\n This randomized, double-blind, placebo-controlled study of 160 patients with asthma who had minimal previous exposure to corticosteroids was conducted from July 1994 through June 1997. Patients received fluticasone at 88 microg twice daily, fluticasone at 440 microg twice daily, or placebo twice daily for 2 years. Bone mineral density (BMD) was evaluated every 6 months by lumbar spine, proximal femur, and total body scans. Measurements of HPA axis function and ophthalmic evaluations were conducted at similar intervals.\n Among the 3 groups, no significant differences were observed in BMD at week 104 (at any anatomical site). Mean percent change from baseline in the lumbar spine was less than 1% for all 3 groups. At all time points, HPA axis function was similar in the 88-microg fluticasone group compared with the placebo group. For mean change from baseline in corticotropin-stimulated peak cortisol (P = .003 and P = .02 at weeks 24 and 52, respectively) and area under the stimulated plasma cortisol vs time curve (P = .002 and P = .02 at weeks 24 and 52, respectively), statistically significant reductions from baseline were observed in the 440-microg fluticasone group compared with the placebo group. These reductions of 10% to 13% from baseline were not accompanied by other signs of systemic effect and did not persist with continued treatment (at weeks 76 and 104). No important ocular changes were observed.\n Long-term treatment with 88 microg of fluticasone twice daily was comparable to placebo in all skeletal, ophthalmic, and HPA axis function assessments. Treatment with fluticasone at 440 microg twice daily resulted in no significant effects on BMD and a statistically significant but not clinically important temporary reduction in cortisol production.", "Inhaled corticosteroids are recommended for the treatment of persistent asthma. Comparative clinical studies evaluating 2 or more doses of these agents are few.\n We sought to compare the efficacy and safety of 2 doses of fluticasone propionate (88 micrograms twice daily and 220 micrograms twice daily) with 2 doses of beclomethasone dipropionate (168 micrograms twice daily and 336 micrograms twice daily) in subjects with persistent asthma.\n Three hundred ninety-nine subjects participated in this randomized, double-blind, parallel-group clinical trial. Eligible subjects were using daily inhaled corticosteroids and had an FEV1 of 45% to 80% of predicted value. Clinic visits, including spirometry, were conducted every 1 to 2 weeks. Subjects recorded symptoms, use of albuterol, and peak expiratory flows on daily diary cards.\n Fluticasone propionate treatment resulted in significantly (P </=.034) greater improvements in objective pulmonary function parameters than did beclomethasone dipropionate treatment and significantly greater reductions in daily albuterol use (P </=.010) and asthma symptoms (P </=.027). Both low-dose (88 micrograms twice daily) and medium-dose (220 micrograms twice daily) fluticasone propionate significantly increased FEV1 compared with higher doses of beclomethasone dipropionate (P =. 006). Low-dose and medium-dose fluticasone propionate improved FEV1 by 0.31 L (14%) and 0.36 L (15%), respectively, compared with improvements of 0.18 L (8%) and 0.21 L (9%) with low-dose and medium-dose beclomethasone dipropionate. The adverse event profiles were similar for both medications.\n Fluticasone propionate provides greater asthma control at roughly half the dose of beclomethasone dipropionate, with a comparable adverse event profile.", "This double-blind, randomized, parallel-group, placebo-controlled study investigated the efficacy and tolerability of fluticasone propionate aerosol (25, 50, or 100 mg bid for 12 weeks) administered as primary maintenance therapy to patients whose mild to moderate asthma was inadequately controlled by as-needed use of an inhaled beta-agonist.\n At all clinic visits, fluticasone propionate compared with placebo was associated with significant (P<.05) improvement in pulmonary function indexed by forced expiratory volume in 1 second (FEV1) as well as fewer night awakenings and less use of rescue albuterol. Values for patient-measured morning peak expiratory flow rates (PEFR) were significantly (P<.05) higher and the use of rescue albuterol was significantly (P<.05) lower beginning 3 to 5 days after initiation of therapy in the groups treated with fluticasone propionate, compared with the placebo group. Maximal improvement in FEV1 was achieved during the second week of treatment and maintained throughout the course of therapy. Differences among the three fluticasone propionate dosing groups for these efficacy measures were not statistically significant. The incidence of adverse events was similar across groups.\n These data indicate that fluticasone propionate aerosol is an effective and well-tolerated treatment for asthma and significantly improves pulmonary function within days of initiation of treatment in patients whose asthma is inadequately controlled with as-needed beta-agonists.", "Fluticasone propionate (FP) administered via metered-dose inhaler is a potent corticosteroid effective in the treatment of asthma. To evaluate the efficacy and safety of FP powder administered via a breath-activated inhaler (Diskhaler), a multicenter, double-blind, randomized, placebo-controlled, parallel-group study was conducted in adolescent and adult patients (n = 331) with mild-to-moderate asthma previously treated with beta 2-agonist therapy alone. Patients received FP powder 50, 100, or 250 micrograms or placebo twice daily for 12 weeks. FP-treated patients compared with placebo-treated patients had significantly (p < 0.001) greater improvements in morning predose forced expiratory volume in 1 sec (21-22% increase vs. 9%). Improvement in morning peak flow rate were also significantly (p < 0.001) greater with FP than with placebo (8-10% increase vs. 2% increase). There was also a significant overall treatment difference in the frequency of inhaled albuterol use (p < 0.001) and number of nighttime awakenings due to asthma (p = 0.005). There were no statistically significant difference among the FP treatment groups in any outcome measure. Physicians' global assessments also indicated significant (p < 0.001) differences in efficacy, with 67-74% of FP-treated patients rated as having \"effective\" or \"very effective\" treatment compared with 41% of placebo-treated patients. Significant beneficial effects of FP were observed in lung function and diary card parameters after just 1 week of treatment. Adverse events were similar across treatment groups and primarily related to local irritation. Effect on hypothalamic-pituitary-adrenal axis function was minimal. In summary, all three dosages of inhaled FP powder were well tolerated and improved various asthma-related variables. Improvements in pulmonary function, beyond those achieved with beta 2-agonist therapy alone, were maintained for the duration of the 12-week study.", "Few dose ranging studies have investigated optimal dosing with inhaled corticosteroids in children with asthma.\n To compare the efficacy and tolerability of fluticasone propionate 100 or 200 microg twice daily in children with moderate to severe asthma for one year.\n One year, randomised, double blind, parallel group, multicentre study. Children aged 4-11 years (n = 528) with moderate to severe asthma who had previously received high dose inhaled corticosteroids were given fluticasone propionate 100 or 200 microg twice daily for the 52 week treatment period. Efficacy (exacerbations, lung function, and symptoms) and tolerability (adverse events and cortisol levels) were measured.\n There was a non-significant decreased risk of experiencing an exacerbation at any time with fluticasone propionate 200 microg twice daily compared with fluticasone propionate 100 microg twice daily. This difference reached significance among patients with more severe asthma (defined by previous inhaled corticosteroid dose >800 microg/day). Daily record card morning peak expiratory flow (PEF) in the total population improved significantly more with the higher dose of fluticasone propionate (between group difference, weeks 1-52: 11.4 l/min). Clinic visit mean PEF improved from baseline with both doses, but the response was significantly greater with the higher dose (between group difference, week 52: 17.8 l/min). Both doses were equally well tolerated and overnight urinary cortisol concentrations were unchanged or slightly increased during treatment with either dose.\n This long term dose comparison study shows that treatment with fluticasone propionate 200 micro g twice daily may offer benefits over a lower dose, particularly in children with more severe asthma.", "Twenty-seven subjects with moderate asthma at the time of diagnosis, well controlled under regular fluticasone propionate (FP) (250 microg b.i.d.) for 6 months at least, were randomized to receive in double-blind fashion: FP 125 microg b.i.d. (Group 1) or FP 50 microg b.i.d. (Group 2) or placebo (Group 3) for 3 months or until symptom recurrence. Daily symptom score and peak expiratory flow were monitored. At the beginning and at the end of the study subjects underwent methacholine challenge and sputum induction. Recurrence of symptoms occurred shortly after randomization in all subjects receiving placebo. None from Group 1 or 2 experienced symptom recurrence during the study. No significant difference in clinical and functional data, and in sputum eosinophil percentages was observed between the beginning and the end of the study in both Groups 1 and 2. Subjects from Group 3 showed a significant increase of sputum eosinophils (P<0.05) and a significant decrease in provocative dose of methacholine (P<0.05) when asthma symptoms recurred. Therefore, very low doses of FP (50 microg b.i.d.) are effective in maintaining for 3 months a good control of the disease in asthmatics already stable under high-dose fluticasone, considering both clinical and functional outcomes and markers of airway inflammation.", "Airway inflammation is now regarded as fundamental in the pathogenesis of asthma and treatment with inhaled corticosteroids has proved effective. There is a need for drugs in this category with higher topical potency but fewer side-effects than those presently available. A double-blind, parallel group study was conducted in 671 patients with severe asthma (already taking between 0.8-2.0 mg of inhaled corticosteroid daily) to compare the safety and efficacy of 6 weeks of treatment with inhaled fluticasone propionate (FP), 1 mg daily, to fluticasone propionate, 2 mg daily, and budesonide (BUD), 1.6 mg daily, delivered via a metered-dose inhaler. Peak expiratory flow (PEF), asthma symptoms, and usage of rescue medication were recorded daily by the patient. At each clinic visit (-2, 0, 3 and 6 weeks) morning serum cortisol levels, bone markers and spirometry were assessed. The changes in mean morning PEF from baseline (weeks 1-6) were: FP 2 mg daily +24 l.min-1; FP 1 mg daily +21 l.min-1; BUD 1.6 mg daily +13 l.min-1. A similar rank order for the three treatments was seen for evening PEF, clinic spirometry, reduction of diurnal PEF variation, symptom scores, and requirement for rescue bronchodilators. The mean serum cortisol levels remained well within the normal range in all three groups. Analysis of the geometric mean cortisol ratio (treatment/baseline ratio after 6 weeks treatment) showed a changed rank order, the values being: FP 1 mg daily 1.04; BUD 1.6 mg daily 0.97; FP 2 mg daily 0.88.(ABSTRACT TRUNCATED AT 250 WORDS)", "The inhaled corticosteroid, fluticasone propionate, was compared with the oral bronchodilator theophylline in the maintenance treatment of asthma.\n The objective of the present study was to compare the efficacy and safety of twice-daily inhaled fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, with that of theophylline in the maintenance treatment of mild-to-moderate asthma.\n In this randomized, double-blind, placebo-controlled, parallel-group study, 353 adult and adolescent patients with asthma inadequately controlled with inhaled beta-agonist therapy alone received fluticasone propionate, 50 micrograms, or fluticasone propionate, 100 micrograms, by metered-dose inhaler; theophylline capsules; or placebo twice daily for 12 weeks. Only inhaled albuterol was permitted as needed for acute symptoms.\n Both fluticasone propionate groups had a significantly greater probability of remaining in the study (ie, meeting asthma stability criteria) than did either the theophylline or placebo group (P < or = .008); 39% and 51% in the theophylline and placebo groups, respectively, were withdrawn due to lack of treatment efficacy compared with 14% and 21% in the fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, groups. Both fluticasone propionate groups experienced significantly greater improvement in FEV1 and PEF compared with patients in the theophylline or placebo group (P < or = .004). The incidence of potentially drug-related adverse events was significantly greater in the theophylline group (25%) than in the placebo group (11%) (P = .031), while there were no differences between placebo and fluticasone propionate, 50 micrograms, (18%) or fluticasone propionate 100 micrograms, (22%).\n Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100 micrograms was significantly more effective than theophylline in the treatment of mild-to-moderate asthma.", "Recent emphasis on the control of airway inflammation in asthma highlights the need for safe and effective antiinflammatory agents. Fluticasone propionate is one of the most potent antiinflammatory corticosteroids developed to date.\n This study assessed the safety and efficacy of fluticasone propionate aerosol in the treatment of mild to moderate asthma.\n Fluticasone propionate aerosol (25, 100, or 500 micrograms twice daily) or placebo was given for as long as 8 weeks to adults with mild to moderate asthma in a randomized, double-blind, parallel-group study. Patients were removed from the study if they showed predefined signs of worsening asthma.\n Sixty-three percent of placebo-treated patients and 23%, 13%, and 4% of patients treated with fluticasone propionate 25, 100, and 500 micrograms twice daily, respectively, were removed from the study. Mean forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow at midexpiratory phase at weekly visits throughout the study demonstrated that fluticasone propionate was more efficacious than placebo in maintaining asthma control. Measurements of peak expiratory flow and symptom scores significantly improved and nighttime awakenings and albuterol use to treat symptoms significantly declined in fluticasone propionate-treated groups relative to the placebo-treated group. Differences among fluticasone propionate groups for these variables were not statistically significant. Incidence and severity of adverse events were similar across groups. Fluticasone propionate did not affect morning or stimulated plasma cortisol concentrations, although slight, transient reductions in urinary free cortisol and urinary 17-hydroxy steroids occurred in the group receiving 500 micrograms fluticasone propionate twice daily.\n These data indicate that fluticasone propionate provides safe and effective treatment for mild to moderate asthma.", "Inhaled corticosteroids are increasingly being used to treat mild-to-moderate asthma in children. However, data regarding therapy with this class of compounds, especially in children under age 6 years, is limited. Fluticasone propionate is a third generation inhaled corticosteroid with an optimal therapeutic index. Few large prospective clinical trials have been conducted to evaluate the efficacy and safety of fluticasone propionate powder in children.\n We sought to determine the efficacy and safety of fluticasone propionate powder administered by means of the Diskus and Diskhaler multidose powder inhalers in pediatric patients with persistent asthma.\n Fluticasone propionate powder (50 microg or 100 microg twice daily) or placebo was administered by means of the Diskus or Diskhaler inhalers to 437 children (4 to 11 years old) with persistent asthma for 12 weeks in a randomized, double-blind, parallel-group, multi-center trial. Patients were stratified according to whether they were receiving prior treatment with inhaled corticosteroids or cromolyn or beta2-agonists alone.\n Fluticasone propionate powder administered by means of Diskus or Diskhaler significantly improved FEV1 (mean increase from baseline of 0.22 to 0.24 L; p < or = 0.023), clinic morning peak expiratory flow (mean increase from baseline of 48 to 55 L/min; p < or = 0.006), patient-measured morning (p < or = 0.001) and evening (p < or = 0.003) peak expiratory flow, and asthma symptom scores (in all but the 50 microg Diskus group; p < or = 0.036), as well as reduced albuterol use (p < or = 0.002) and nighttime awakenings (p < or = 0.019) at endpoint. Efficacy parameters were not significantly different between the two doses with either device. More placebo-treated patients discontinued the study because of lack of efficacy than patients in any fluticasone propionate group (p < 0.001). Fluticasone propionate did not suppress morning plasma cortisol concentrations and did not affect 24-hour urinary free-cortisol excretion. Adverse events were primarily pharmacologic effects of inhaled corticosteroids, and those related to the study drug occurred with low frequency. Patient satisfaction with both the Diskus and Diskhaler devices was high, with a majority of patients (> 80%) rating them favorably.\n This study demonstrated that fluticasone propionate powder, at the conventional recommended doses of up to 200 microg/day administered by means of Diskus or Diskhaler, was well tolerated and improved lung function in children even as young as 4 and 5 years old regardless of whether they were previously treated with inhaled corticosteroids or cromolyn or beta2-agonists alone.", "Many patients with severe asthma are dependent on oral corticosteroids for maintenance control of their disease. Treatments that allow patients to be weaned off oral corticosteroids may help to minimize the risk of side effects associated with their chronic use.\n This study evaluated whether inhaled fluticasone propionate powder could maintain pulmonary function while reducing the dose of oral prednisone in patients with chronic, severe asthma.\n Oral prednisone-dependent (5 to 40 mg/day) adolescents and adults with asthma (n = 111; mean FEV1 = 61% of predicted value) were randomized to placebo or twice daily fluticasone propionate 500 or 1000 microg administered by means of a multidose powder inhaler for 16 weeks in a double-blind, parallel-group study. Patients underwent controlled prednisone reduction on the basis of predetermined asthma stability criteria.\n Oral prednisone was eliminated by 75% and 89% of patients in the twice daily 500 and 1000 microg fluticasone propionate groups, respectively, versus 9% of the placebo group (P <.001). FEV1, morning and evening peak expiratory flow, asthma symptoms, albuterol use, and nighttime awakenings improved with fluticasone propionate treatment, achieving statistical significance (P </=.009) primarily in the 1000 microg twice daily group. Hypothalamic-pituitary-adrenal axis suppression observed at baseline improved when patients were weaned off oral prednisone to fluticasone propionate. Adverse events ascribed to drug treatment were primarily topical effects of inhaled corticosteroids or those associated with prednisone withdrawal. Patient quality of life assessed by means of the Asthma Quality of Life Questionnaire was clinically and significantly improved after fluticasone propionate treatment (P </=.003).\n Fluticasone propionate powder (500 or 1000 microg twice daily) effectively improved lung function, adrenal function, and asthma-specific quality of life in patients with severe chronic asthma previously treated with oral prednisone while allowing most patients to be weaned off oral corticosteroid therapy.", "The aim of this multicenter, double-masked study was to compare the efficacy and safety of two different doses of inhaled fluticasone propionate dry powder--50 micrograms and 100 micrograms--administered BID via a multidose powder inhaler with those of placebo in the treatment of children with persistent asthma. After a 2-week run-in period, 263 patients were randomized to treatment with twice-daily placebo (n = 92), fluticasone 50 micrograms (n = 85), or fluticasone 100 micrograms (n = 86) for 12 weeks. One hundred sixty-six (63%) patients were male, and 224 (85%) were white, with a mean age of 8 years. Two hundred twenty-one (84%) patients were atopic, and 167 (63%) had been asthmatic for 1 to 5 years. Baseline mean morning peak expiratory flow (PEF) values were 207 L/min, 199 L/min, and 194 L/min, and baseline percentages of predicted normal values were 86%, 80%, and 81% for the groups receiving placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. At the end of the first week of treatment, patients in both fluticasone groups had significantly greater improvements in morning PEF than did those receiving placebo. Patients experienced mean increases of 4 L/min, 22 L/min, and 26 L/min with placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. At the end point (the last evaluable visit), patients in both fluticasone groups continued to have significantly greater improvements in morning PEF than did patients receiving placebo. Patients experienced mean increases of 17 L/min, 50 L/min, and 57 L/min with placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. Changes in the percentage of predicted values by end point were 8%, 20%, and 26% with placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. The probability of remaining in the study, according to predefined withdrawal criteria, indicated a significant treatment difference in favor of fluticasone. Withdrawal criteria were met by 63%, 42%, and 29% of patients receiving placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. This study clearly demonstrates the superiority of fluticasone 50 and 100 micrograms BID over placebo in the treatment of persistent asthma in children.", "Inhaled corticosteroids (ICS) are typically associated with a flat dose-response curve when traditional efficacy values are examined (eg, FEV(1)). The aim of the present study was to investigate if a dose-response relationship exists for lung function and inflammatory cell numbers in bronchial biopsy specimens.\n Bronchial biopsy specimens were obtained from 36 patients randomized to receive 100 micro g, 500 microg, or 2,000 microg/d of fluticasone propionate (FP). Lung physiology and bronchial biopsies were performed at baseline and after 2 weeks of treatment.\n Improvement in lung function and suppression of airway inflammation were optimal at a dose of 500 microg/d of FP. Significant changes from baseline following treatment were documented in FEV(1) (p = 0.02), forced expiratory flow (p = 0.002), FEV(1)/FVC (p = 0.007), provocative concentration of histamine causing a 20% fall in FEV(1) (PC(20)) [p = 0.02], T-cell numbers (p = 0.0005), activated eosinophils (p = 0.01), and numbers of macrophages (p = 0.01) in the group treated with 500 microg/d of FP. Comparison between groups administered different doses of FP failed to demonstrate a dose-response relationship for change from baseline in PC(20) (p = 0.43), any of the lung function parameters, T-cell numbers (p = 0.64), activated T cells (p = 0.46), eosinophils (p = 0.53), activated eosinophils (p = 0.48), or macrophage numbers (p = 0.68).\n The apparent lack of a dose-response for ICS treatment in patients with asthma further validates the preferential use of add-on therapy over increasing the dose of ICS.", "To determine whether inhaled fluticasone propionate has long-term effects on growth in children with persistent asthma.\n In a double-blind, randomized, parallel-group, multicenter study, 325 prepubescent children with persistent asthma and normal growth rates were treated with placebo or inhaled fluticasone propionate powder 50 microg or 100 microg administered twice daily by a breath-actuated device for 1 year. Growth was evaluated monthly, whereas other safety variables and pulmonary function were evaluated periodically.\n The prepubescent patients showed no statistically significant differences in mean height, mean growth velocity, or mean skeletal age between any of the treatment groups at any time. Over a period of 1 year, mean height (+/- SE) increased 6.15 +/- 0.17 cm in the placebo group, 5.94 +/- 0.16 cm in the fluticasone propionate 50 microg group, and 5.73 +/- 0.13 cm in the fluticasone propionate 100 microg group (p = 0.308, overall).\n Prepubescent children treated with fluticasone propionate 50 microg and 100 microg administered twice daily for 1 year grew at rates similar to placebo-treated control subjects and at rates equal to expected growth velocity for age.", "Many clinicians are reluctant to prescribe inhaled corticosteroids because of concerns over potential effects on the hypothalamic-pituitary-adrenal axis.\n The purpose of this study was to compare the adrenal responses to 6-hour cosyntropin infusion after treatment with fluticasone propionate aerosol, triamcinolone acetonide aerosol, prednisone, and placebo for 4 weeks, a sufficient time interval to assess any effects on the adrenal response to stress.\n This double-blind, triple-dummy, randomized, placebo-controlled study was conducted in 128 patients to evaluate adrenal response to 6-hour cosyntropin infusion (a clinically relevant method for evaluating adrenal function) after 28 days of treatment with fluticasone propionate aerosol 88 microg or 220 microg twice daily, triamcinolone acetonide aerosol 200 microg 4 times daily or 400 microg twice daily, prednisone 10 mg once daily, and placebo.\n After 28 days of treatment, mean plasma cortisol response to cosyntropin over 12 hours after initiation of the 6-hour infusion was similar among fluticasone, triamcinolone, and placebo groups; cortisol response was significantly (P <.05) reduced after treatment with prednisone compared with the other treatment groups. Mean 8-hour area under the plasma cortisol concentration-time curves and peak plasma cortisol concentrations were significantly (P </=.003) lower with prednisone than any other treatment; no significant differences were noted between placebo and either of the fluticasone groups in any assessment. Mean reductions from baseline in area under the plasma cortisol concentration time curves and peak cortisol concentrations were significantly (P <.05) greater with triamcinolone 400 microg twice daily compared with placebo.\n These results suggest that fluticasone propionate at therapeutic doses has effects on the hypothalamic-pituitary-adrenal axis comparable to that of placebo and has significantly less effect than prednisone as measured by 6-hour cosyntropin infusion after 28 days of treatment.", "The dose dependency of the effects of inhaled corticosteroids on markers of asthmatic airway inflammation have not been well studied. There is a need to study the dose/response effects on this inflammation. In order to determine the dose/response effects of fluticasone propionate (FP), 24 asthmatic subjects were randomized to low- (100 microg x day(-1)) or high-dose (1,000 microg x day(-1)) FP for six weeks followed by placebo for 3 weeks. During treatment, the median increase in forced expiratory volume in one second (FEV1)was 12% in the high-dose group (p<0.05) and 10% in the low-dose group (p<0.05) (p>0.05 between groups); the median decrease in the percentage of sputum eosinophils was 93% in the high-dose group (p<0.05) and 46% in the low-dose group (p<0.05) (p>0.05 between groups). Symptoms, salbutamol use, morning peak flow, provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophil cationic protein concentration and tryptase activity improved significantly in both groups (p<0.05), but only the improvement in salbutamol use was greater in the high-dose group (p<0.05). During the run-out, the improvements in FEV1 and PC20 were rapidly reversed in both groups, but the improvements in peak flow and tryptase activity persisted; the improvement in sputum eosinophil concentration persisted only in the high-dose group (p<0.05). It was concluded that dose/response effects for FP are not easily demonstrable because low-dose FP is quite effective. For most outcomes, the effects of high- and low-dose FP are relatively short-lived after treatment is stopped. This finding raises questions about the extent to which inhaled corticosteroids are disease-modifying in asthma.", "This dose-ranging study evaluated the clinical efficacy and safety of inhaled fluticasone propionate administered once daily via a multidose powder inhaler in patients with moderate asthma (FEV(1), 45 to 75% predicted).\n In this multicenter trial, 330 patients (> or = 12 years old) previously receiving inhaled corticosteroids or beta(2)-agonists alone were randomized in a double-blind manner to receive fluticasone propionate at 100, 200, or 500 microg once daily or matching placebo for 12 weeks.\n Once-daily treatment with fluticasone propionate resulted in an improvement in efficacy variables, such as FEV(1), morning and evening peak expiratory flow (PEF), asthma symptom scores, nighttime awakenings, albuterol use, and duration of study participation. A dose-related trend was observed for improvements in morning and evening PEF and albuterol use. Statistical significance for pairwise comparisons was achieved for 200 microg and 500 microg fluticasone propionate vs placebo for all efficacy variables, and for 100 microg fluticasone propionate vs placebo for morning and evening PEF at most or all time points. Drug-related adverse events were few (< or = 5%) and mostly related to the topical effects of inhaled corticosteroids. No dose-response effect or clinically relevant differences were observed in morning plasma cortisol concentrations or after cosyntropin stimulation.\n Once-daily treatment with fluticasone propionate was well tolerated and demonstrated some dose-related trends in improvements in lung function and asthma control in patients with moderate asthma.", "This study was undertaken to evaluate the efficacy and safety of fluticasone propionate, an inhaled corticosteroid, in adolescents and adults with moderate asthma who were previously taking inhaled corticosteroids. After a 2-week, open-label screening period, a double-masked, randomized, parallel-group, dose-ranging study was conducted over 12 weeks in 21 outpatient centers throughout the United States. Patients (N = 304) > or = 12 years of age with moderate asthma previously treated with inhaled corticosteroids and beta-sympathomimetic bronchodilators were enrolled. Patients were assigned to receive placebo or fluticasone propionate 100, 250, or 500 micrograms twice daily via a metered-dose inhaler without a spacer device. These doses refer to the amount of fluticasone propionate released from the valve of the metered-dose inhaler; the corresponding doses released from the activator of the metered-dose inhaler are 88 micrograms, 220 micrograms, and 440 micrograms, respectively. Between baseline and end point, mean values of forced expiratory volume in 1 second decreased 0.31 L in the placebo group and improved 0.39 L, 0.30 L, and 0.43 L in patients receiving 100-micrograms, 250-micrograms, and 500-micrograms fluticasone propionate, respectively. The differences between placebo and all treatment groups were statistically significant. More patients were withdrawn from placebo (72%) than from fluticasone propionate (13% to 16%) because of failure to meet predetermined asthma stability criteria. Differences in baseline-to-end point changes in morning peak expiratory flow rate, physician overall assessments and patient-rated assessment of symptoms, and albuterol use for symptom control also significantly favored each fluticasone propionate group over placebo. There were essentially no differences in efficacy among the three fluticasone propionate groups. Treatment-related adverse events occurred in 8% of placebo-treated patients and 13% to 15% of fluticasone propionate-treated patients; these events were mainly localized to the oropharynx/ larynx. A 12-week course of fluticasone propionate (100, 250, and 500 micrograms twice daily) was well tolerated and more effective than placebo based on maintenance of asthma stability, pulmonary function tests, physician and patient assessments, and rescue bronchodilator use. No dose-related effects were observed with the dosages of fluticasone propionate used in this study.", "Dose-response relationships with inhaled corticosteroids in the treatment of asthma have been difficult to establish. A multicenter, double-blind, parallel-group study was conducted to evaluate the clinical efficacy and safety of low doses of inhaled fluticasone propionate (FP) in patients with mild to moderate asthma. Methacholine challenge testing was conducted in addition to measurement of traditional efficacy variables. After a single-blind screening period, 138 patients > or = 12 years of age were randomly assigned to receive placebo, FP 50 microg, or FP 100 microg, twice daily for 8 weeks. The results of methacholine challenge testing averaged over all visits favored FP 200 microg/day over placebo and FP 100 microg/day (p < 0.05); there were no significant differences between placebo and FP 100 microg/day. Mean changes from baseline to endpoint favored each dose of FP over placebo based on forced expiratory volume in 1 sec (FEV1), patient-measured peak expiratory flow (PEF), total symptom scores, and rescue bronchodilator use (p < 0.05); there were no differences in these parameters between the two doses of FP. The addition of methacholine challenge testing allowed definition of a dose-response relationship that was not apparent with traditional efficacy variables.", "We assessed the systemic effects of budesonide (BUD) and fluticasone propionate (FP) in 23 patients with asthma, using a double-blind, placebo-controlled, double-dummy, and cross-over design. The following five treatments were given in a randomized order for 1 wk with a washout period in between of 2 wk: (1) placebo; (2) FP, 200 micrograms twice a day, inhaled from a Diskhaler; (3) FP, 1,000 micrograms twice a day, inhaled from a Diskhaler; (4) BUD, 200 micrograms twice a day, inhaled from a Turbuhaler; and (5) BUD, 800 micrograms twice a day, inhaled from a Turbuhaler. The primary variable was the area under the curve of serum cortisol versus time (AUC0-20), derived from serum samples taken every 2 h over a 20-h period following the last evening dose at 10:00 P.M. The lower doses of BUD and FLU did not cause any adrenal suppression. Compared with placebo, however, FP (1, 000 micrograms, twice daily and BUD (800 micrograms, twice daily) decreased the AUC0-20 by 34 and 16%, respectively. Fluticasone (1,000 micrograms, twice daily) was more suppressive than BUD (800 micrograms, twice daily) (p = 0.0006). The FEV1, measured the morning after the last inhalation, was significantly higher after the active treatments, compared with placebo (p < 0.02), but did not differ between all active treatments. We conclude that high doses of BUD and FP (in particular the latter), inhaled via their respective dry powder inhalers for 1 wk, result in a measurable systemic activity in patients with asthma.", "In this randomized, double-blind, placebo-controlled trial, 397 patients with moderate to severe asthma, previously treated with bronchodilators alone, received fluticasone propionate 88, 220, or 440 microg twice daily, or placebo via metered dose inhaler (MDI) for 12 weeks. Mean change from baseline to endpoint in pre-dose percent predicted forced expiratory volume in one second (FEV1) was greater (p < 0.001) in each fluticasone propionate group (9.0%, 88 microg bid; 9.8%, 220 microg bid; 11.2%, 440 microg bid) versus placebo (3.4%). Morning and evening peak expiratory flow (PEF), asthma symptoms, and supplemental albuterol use also improved in all fluticasone propionate groups versus placebo. The incidence of adverse events and 24-hour urine cortisol excretion rates were similar between active treatments and placebo.", "This study examined the ability of fluticasone propionate aerosol to reduce oral prednisone requirements in patients with severe asthma. Ninety-six patients dependent on oral prednisone were treated for 16 wk with placebo or fluticasone propionate aerosol (750 or 1,000 micrograms twice daily). Their dosage of oral prednisone was adjusted weekly according to predetermined criteria. A total of 69% and 88% of patients treated with fluticasone propionate 750 and 1,000 micrograms twice daily, respectively, compared with 3% of placebo-treated patients used no prednisone by the end of the study. In the fluticasone propionate groups, FEV1 and peak expiratory flow rates at the last evaluable visit/date improved and the number of night awakenings and symptomatic albuterol use declined relative to placebo values (p < 0.05). Patient-rated asthma symptoms improved in the groups receiving fluticasone propionate but not in the placebo group (p < 0.005). Fluticasone propionate aerosol was well-tolerated, and it improved some dimensions of health-related quality of life measured using a standard patient survey. Fluticasone propionate aerosol (750 or 1,000 micrograms twice daily) effectively and safely allowed most asthmatics dependent on oral corticosteroids to reduce or eliminate oral prednisone use while improving pulmonary function and quality of life." ]

[ "11408301", "12583945", "12946338" ]

[ "Randomised controlled trial of cardiotocography versus Doppler auscultation of fetal heart at admission in labour in low risk obstetric population.", "Admission cardiotocography: a randomised controlled trial.", "A randomised controlled trial of admission electronic fetal monitoring in normal labour." ]

[ "To compare the effect of admission cardiotocography and Doppler auscultation of the fetal heart on neonatal outcome and levels of obstetric intervention in a low risk obstetric population.\n Randomised controlled trial.\n Obstetric unit of teaching hospital\n Pregnant women who had no obstetric complications that warranted continuous monitoring of fetal heart rate in labour.\n Women were randomised to receive either cardiotocography or Doppler auscultation of the fetal heart when they were admitted in spontaneous uncomplicated labour.\n The primary outcome measure was umbilical arterial metabolic acidosis. Secondary outcome measures included other measures of condition at birth and obstetric intervention.\n There were no significant differences in the incidence of metabolic acidosis or any other measure of neonatal outcome among women who remained at low risk when they were admitted in labour. However, compared with women who received Doppler auscultation, women who had admission cardiotocography were significantly more likely to have continuous fetal heart rate monitoring in labour (odds ratio 1.49, 95% confidence interval 1.26 to 1.76), augmentation of labour (1.26, 1.02 to 1.56), epidural analgesia (1.33, 1.10 to 1.61), and operative delivery (1.36, 1.12 to 1.65).\n Compared with Doppler auscultation of the fetal heart, admission cardiotocography does not benefit neonatal outcome in low risk women. Its use results in increased obstetric intervention, including operative delivery.", "Admission cardiotocography is widely used to identify pregnancies that might benefit from continuous electronic fetal monitoring in labour. We aimed to compare the effect on neonatal outcome of admission cardiotocography versus intermittent auscultation of the fetal heart rate.\n 8580 women admitted to the delivery ward of a Dublin teaching hospital who were at low risk of fetal distress in labour were randomly assigned admission cardiotocography (20 min) or the unit's usual care (intermittent auscultation only, with continuous cardiotocography only if clinically indicated). The primary outcome was moderate to severe neonatal morbidity, or perinatal mortality in the absence of a major congenital malformation. Analyses were by intention to treat.\n 44 (1.0%) women assigned admission cardiotocography did not undergo the procedure; 15 (0.4%) assigned usual care had admission cardiotocography. The primary endpoint occurred in 56 (1.3%) of 4298 women assigned admission cardiotocography and 55 (1.3%) of 4282 in the usual-care group (relative risk 1.01; 95% CI 0.70-1.47). Other indices of neonatal morbidity also showed no differences. Despite an increase in use of continuous cardiotocography (1.39; 1.33-1.45) and fetal blood sampling (1.30; 1.14-1.47) with admission cardiotocography, there were no significant differences in the rates of caesarean delivery (1.13; 0.92-1.40), instrumental delivery (1.03; 0.92-1.16), or episiotomy (1.06; 0.99-1.13).\n Routine use of cardiotocography for 20 min on admission to the delivery ward does not improve neonatal outcome. No significant increase in operative delivery was apparent, probably because of liberal use of fetal blood sampling.", "To test the hypothesis that the use of admission Electronic Fetal Monitoring (EFM) for healthy pregnant women in spontaneous labour would result in an increase in continuous EFM when compared to women who have had no admission EFM.\n A randomised controlled trial.\n The Midwives Birth Unit in Glasgow Royal Maternity Hospital, a major urban teaching hospital with approximately 5000 births per year.\n Healthy pregnant women admitted in normal labour, deemed low risk based on the midwives' birth unit admission criteria.\n Women were randomly allocated either to receive a routine 20-minute period of EFM at the time of admission (control group), or to receive no routine admission EFM (study group).\n Primary study outcomes, use of continuous EFM; and use of EFM additional to the admission test. Secondary outcomes: artificial rupture of membranes, use of fetal scalp electrode, fetal blood sample, syntocinon, epidural analgesia, number of vaginal examinations, rate of transfer to labour ward, and reason for transfer.\n There was no statistically significant difference between the groups for use of continuous monitoring, but significantly more women in the control group did receive additional EFM. There was no statistically significant difference between groups for any of the interventions studied.\n The use of admission EFM did not in itself lead to a cascade of intervention. Other factors including setting of care and philosophy of caregivers may have an effect on the rate of intervention in labour." ]

[ "1320133", "9709043" ]

[ "Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes.", "A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases." ]

[ "To determine the efficacy of the nonoxynol 9 contraceptive sponge in preventing sexual acquisition of the human immunodeficiency virus (HIV).\n Prospective, randomized placebo-controlled trial.\n Research clinic for prostitutes in Nairobi, Kenya.\n One hundred thirty-eight HIV-seronegative women were enrolled, of whom 74 were assigned to nonoxynol 9 sponge use and 64 to placebo use. These two groups did not significantly differ with respect to demographic characteristics, sexual practices, or prevalence of genital infections at enrollment, except for a lower number of sex partners per week and a higher initial prevalence of genital ulcers among women assigned to nonoxynol 9 sponge use. Among the 116 women who returned for follow-up, the mean durations of follow-up were 14 and 17 months for the two groups, respectively.\n HIV seroconversion.\n Nonoxynol 9 sponge use was associated with an increased frequency of genital ulcers (relative risk [RR], 3.3; P less than .0001) and vulvitis (RR, 3.3; P less than .0001) and a reduced risk of gonococcal cervicitis (RR, 0.4; P less than .0001). Twenty-seven (45%) of 60 women in the nonoxynol 9 sponge group and 20 (36%) of 56 women in the placebo group developed HIV antibodies. The hazard ratio for the association between nonoxynol 9 sponge use and HIV seroconversion was 1.7 (95% confidence interval [CI], 0.9 to 3.0). Using multivariate analysis to control for the presence of genital ulcers at enrollment, the adjusted hazard ratio for the association between nonoxynol 9 sponge use and seroconversion was 1.6 (95% CI, 0.8 to 2.8).\n Genital ulcers and vulvitis occurred with increased frequency in nonoxynol 9 sponge users. We were unable to demonstrate that nonoxynol 9 sponge use was effective in reducing the risk of HIV infection among highly exposed women.", "Nonoxynol 9 is a proved spermicide, but whether it is also a microbicide is uncertain. A truly effective vaginal microbicide would reduce the susceptibility of women to sexually transmitted diseases, including infection with the human immunodeficiency virus (HIV).\n We enrolled 1292 HIV-negative female sex workers in Cameroon and enrolled them in a double-blind, placebo-controlled study in which the participants were randomly assigned to use either a film containing 70 mg of nonoxynol 9 or a placebo film, inserted into the vagina before intercourse. All of the women were provided with latex condoms and were instructed to have their male sexual partners use them. At monthly follow-up visits, we examined the women with a colposcope for genital lesions, tested endocervical specimens for gonorrhea and chlamydia infection with DNA probes, tested for HIV infection, and treated the women for curable sexually transmitted diseases.\n The rates of HIV infection (cases per 100 woman-years) were 6.7 in the nonoxynol 9 group and 6.6 in the placebo group (rate ratio, 1.0; 95 percent confidence interval, 0.7 to 1.5). The rates of genital lesions were 42.2 cases per 100 woman-years in the nonoxynol 9 group and 33.5 in the placebo group (rate ratio, 1.3; 95 percent confidence interval, 1.0 to 1.6). The rates of gonorrhea were 33.3 and 31.1 cases per 100 woman-years in the nonoxynol 9 and placebo groups, respectively (rate ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4). The corresponding rates of chlamydia infection in the nonoxynol 9 group and the placebo group were 20.6 and 22.2 per 100 woman-years (rate ratio, 0.9; 95 percent confidence interval, 0.7 to 1.3). The women reported that condoms were used during 90 percent of sexual acts.\n The use of a nonoxynol 9 vaginal film did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in this group of sex workers who used condoms and received treatment for sexually transmitted diseases." ]

[ "16962532", "9609272", "12623472", "2558705", "9463178", "20680312", "12103284", "18506347", "342330", "19187377", "6255654", "3011061", "18271883" ]

[ "A randomized comparison of suturing techniques for episiotomy and laceration repair after spontaneous vaginal birth.", "The Ipswich Childbirth Study: 1. A randomised evaluation of two stage postpartum perineal repair leaving the skin unsutured.", "A multicentre evaluation of the two-layered repair of postpartum perineal trauma.", "The Southmead perineal suture study. A randomized comparison of suture materials and suturing techniques for repair of perineal trauma.", "[Selective episiotomy. Comparison of two suture technics].", "Continuous versus interrupted episiotomy repair with monofilament or multifilament absorbed suture materials: a randomised controlled trial.", "Continuous versus interrupted perineal repair with standard or rapidly absorbed sutures after spontaneous vaginal birth: a randomised controlled trial.", "Randomized controlled clinical trial on two perineal trauma suture techniques in normal delivery.", "[A comparison between chromic catgut and polyglycolic acid sutures in episiotomy repair (author's transl)].", "Continuous versus interrupted sutures for repair of episiotomy or second-degree perineal tears: a randomised controlled trial.", "[Intradermal suturing compared with interrupted sutures in episiotomy].", "Episiotomy repair--immediate and long-term sequelae. A prospective randomized study of three different methods of repair.", "Postpartum perineal repair performed by midwives: a randomised trial comparing two suture techniques leaving the skin unsutured." ]

[ "To compare the continuous knotless technique of perineal repair with the interrupted method after spontaneous vaginal birth\n A randomized controlled trial.\n Canadian Task Force Classification I.\n This study was undertaken in a university hospital with more than 2200 deliveries per year. The static population of this district includes a wide range of socioeconomic classes and is predominately white.\n From May 1 to November 19, 2003, 214 primiparous women with a second-degree perineal tear or episiotomy were randomly allocated to either the continuous knotless technique (CKT; n=107) or the interrupted technique (IT; n=107) suturing method.\n The interrupted technique (IT) involves placing 3 layers of sutures whereas the continuous knotless technique (CKT) involves reapproximating vaginal trauma, perineal muscles, and skin with a loose, continuous, nonlocking technique.\n The primary outcomes of the study were perineal pain (evaluated by visual analogue scale) at 48 hours and day 10 and dyspareunia 3 months after delivery. Secondary outcomes included suture removal, wound dehiscence, analgesia use up to 48 hours, and satisfaction with repair established at 3 and 12 months after childbirth. At day 10, 19 women had dropped out of the study. Significantly fewer women reported pain at 10 days with the CKT than with the IT (32.3% vs 60.4%; p<.001). Analgesia use up to 48 hours postpartum was less in the CKT group than in the IT group (33.6% vs 54.2%; p<.05). No difference was found in superficial dyspareunia at 3 months for the CKT versus the IT group.\n The use of a continuous knotless technique for perineal repair is associated with less short-term pain than techniques with interrupted sutures.", "To evaluate a policy of two stage postpartum perineal repair leaving the skin unsutured.\n A stratified randomised controlled trial using a 2 x 2 factorial design.\n The maternity unit at Ipswich Hospital NHS Trust, a district general hospital, between 1992 and 1994.\n 1780 women requiring surgical repair of episiotomy or first or second degree tear following a spontaneous or simple instrumental delivery.\n A policy of two-stage perineal repair leaving skin unsutured was compared with a policy of three stage repair including skin closure with interrupted or subcuticular sutures. Both groups were assessed by a research midwife, blind to the allocation, completing questionnaires at 24 to 48 hours and 10 days postpartum, and by self-completed questionnaires at three months after birth.\n 1. 24 to 48 hours postpartum: perineal pain; healing; 2. 10 days postpartum: perineal pain, healing and removal of sutures; 3. three months postpartum: perineal pain, removal of sutures, resuturing, dyspareunia, and failure to resume pain-free intercourse.\n Completed questionnaires were returned for 99% of women at both 24 to 48 hours and ten days and by 93% of women three months postpartum. No differences were detected in perineal pain at 24 to 48 hours (62% vs 64%; RR 0.96, 95% CI 0.90-1.03; 2P = 0.3) and 10 days (25% vs 28%; RR 0.90, 95% CI 0.77-1.06; 2P = 0.2). Significantly fewer women allocated to two-stage repair reported tight stitches at ten days (14% vs 18%; RR 0.77, 95% CI 0.62-0.96, 2P = 0.02); similar numbers of repairs were judged to be breaking down (five compared with seven women). At three months postpartum fewer women allocated to the two-stage repair reported perineal pain and more had resumed pain-free intercourse. Amongst women who had resumed intercourse there was a significant difference in dyspareunia (15% vs 19%; RR 0.80, 95% CI 0.65-0.99; 2P = 0.04). Significantly fewer women in the two-stage repair group (7% vs 12%; RR 0.61, 95% CI 0.45-0.83; 2P = < 0.01) reported removal of suture material. Four women in the two-stage repair group had required resuturing, compared with nine allocated to the three-stage repair.\n Two-stage repair of perineal trauma leaving the skin unsutured appears to reduce pain and dyspareunia three months postpartum. There are no apparent disadvantages, in particular no evidence of an increased risk of breakdown of the repair and resuturing.", "We set out to compare a policy of two-layered postpartum perineal repair leaving the skin unsutured with a policy of three-layered repair, which involved skin closure. Parturients who sustained a second-degree tear or an episiotomy in four Nigerian centers were randomised to have either a two-layered repair (417 women) or a three-layered repair (406 women). Fewer women in the two-layered group reported perineal pain at 48 hours (57% vs. 65%, relative risk [RR] 0.87, 95% confidence interval [CI] 0.78-0.97) and 14 days postpartum (22% vs. 28%, RR 0.77, CI 0.61-0.98). The two-layered repair was also associated with reduced risk of suture removal (6% vs. 10%, RR 0.62, CI 0.39-0.99), and less superficial dyspareunia at 3 months (6% vs. 12%, RR 0.52, CI 0.33-0.81). The rates of wound healing were similar between the two groups. Leaving the skin unsutured during postpartum perineal repair reduces perineal pain and dyspareunia.", "Commonly used suture materials and techniques for perineal repair following vaginal delivery were compared in a randomized controlled trial involving 1574 women. Three comparisons were made using a modified factorial design. In the comparison of teflon-coated polyglycolic acid (Dexon plus) with chromic catgut for repair of the vagina and deep perineal tissues there was no clear difference other than less short-term analgesia being required in association with polyglycolic acid. Outcome was also similar after skin repair with either polyglycolic acid or chromic catgut or silk, although silk repair required more packets of material and was associated with delay in resuming sexual intercourse; polyglycolic acid was more likely to need removal than chromic catgut but it appeared to reduce the need for resuturing. There was no clear difference between continuous subcuticular and interrupted transcutaneous sutures for repair of perineal skin.", "The study aimed to highlight any differences between the sequelae of episiorrhaphy performed using the Blair-Donatti and Guilmen-Pontonnier techniques.\n A total of 202 pregnant women were recruited in the Obstetrics Ward of Codogno Civic Hospital in 1994 and 1995. Subjects were randomly divided into two groups matched for socioeconomic status, age and parity (group A: Guilmen-Pontonnier suture, group B: Blair-Donatti suture). The following parameters were evaluated: pain twenty-four hours, sixty-six hours and one, two and three months after labour, pain during sexual relations, the onset of infection, hematoma, dehiscence of the wound, and lastly the cosmetic results.\n No significant differences were found between the parameters examined in both groups, barring the improved cosmetic result in group A.", "To compare different repair techniques and different suture materials for episiotomy.\n 160 women having vertex delivery with right-mediolateral episiotomy were randomly allocated to four groups. In the groups where continuos technique was performed, vaginal mucosa, perineal muscles and the skin were sutured continuously. In the groups of interrupted technique, vaginal mucosa was sutured with continuous sutures, then muscle layers and skin were closed by interrupted sutures. Two different types of synthetic absorbed suture material were used: monofilament type is in form of polyglycolide-co-caprolactone and multifilament one is polyglactin 910-Rapide. Perineal pain during different activities on the first and tenth day postpartum and also during sexual intercourse 6 weeks after the delivery was questioned by visual analogous scale (VAS). Furthermore, repair time, amount of suture and episiotomy complications were investigated in each groups.\n On the first day after delivery, the perineal pain scores, the repair time, the amount of suture were statistically less in the continuous technique groups. The differences between the pain at tenth day and during sexual intercourse 6 weeks after the delivery were statistically same.\n The continuous suturing techniques for episiotomy closure, compared to interrupted methods, are associated with less short-term pain, are quicker and also need less suture material.", "Trauma to the perineum is a serious and frequent problem after childbirth, with about 350000 women each year in the UK needing sutures for perineal injury after spontaneous vaginal delivery, and many millions more worldwide. We compared the continuous technique of perineal repair with the interrupted method, and the more rapidly absorbed polyglactin 910 suture material with the standard polyglactin 910 material.\n 1542 women who had a spontaneous vaginal delivery with a second-degree perineal tear or episiotomy were randomly allocated to either the continuous (n=771) or interrupted (771) suturing method, and to either the more rapidly absorbed polyglactin 910 suture material (772) or standard polyglactin 910 material (770). Primary outcomes were pain 10 days after delivery and superficial dyspareunia 3 months postpartum. Analysis was by intention to treat.\n At day 10, three women had dropped out of the study. Significantly fewer women reported pain at 10 days with the continuous technique than with the interrupted method (204/770 [26.5%] vs 338/769 [44.0%], odds ratio 0.47, 95% CI 0.38-0.58, p<0.0001). Occurrence of pain did not differ significantly between groups assigned the more rapidly absorbed material or standard material (256/769 [33.3%] vs 286/770 [37.1%], 0.84, 0.68-1.04, p=0.10). Women reported no difference in superficial dyspareunia at 3 months for the continuous vs the interrupted method (98/581 [16.9%] vs 102/593 [17.2%], 0.98, 0.72-1.33, p=0.88) or the more rapidly absorbed versus standard material (105/586 [17.9%] vs 95/588 [16.2%], 1.13, 0.84-1.54, p=0.42). Suture removal was done less with the more rapidly absorbed material than with standard suture material (22/769 [3%] vs 98/770 [13%], p<0.0001), and with the continuous versus interrupted method (24/770 [3%] vs 96/769 [12%], p<0.0001).\n A simple and widely practicable continuous repair technique can prevent one woman in six from having pain at 10 days. Also, the more rapidly absorbed polyglactin 910 material obviates need for suture removal up to 3 months postpartum for one in ten women sutured.", "The aim was to compare healing and perineal pain with the use of continuous and interrupted suture techniques in women after normal delivery. A randomized controlled trial was carried out at a hospital birth center in Itapecirica da Serra, Sao Paulo, Brazil. A total of 61 women participated with episiotomy or second degree perineal tear, allocated in two groups according to the continuous (n=31) or interrupted (n=30) suture techniques. The main outcomes evaluated were edema, ecchymosis, hyperemia, secretion, dehiscence, fibrosis, frequency and degree of pain (evaluated by numerical scale from 1 to 10). Data were collected during hospitalization and after discharge (four and 41 days after birth). Healing occurred by first intention in 100% of cases in both suture techniques. There were no statistically significant differences for the occurrence of morbidities, except for perineal pain due to palpation at four days after delivery, which was more frequent among women with interrupted suture.", "Polyglycolic acid sutures (Dexon) were compared to chromic catgut sutures in episiotomy repair. When polyglycolic acid sutures were used, the degree of postpartum perineal pain was approximately half as great, and the incidence of dehiscence of episiotomy was 3--5 times greater in the chromic catgut group. The cosmetic results 3 months postpartum were clearly better by using Dexon sutures, especially when the perineal skin was closed by a continuous intracutaneous suture.", "To evaluate the repair techniques of continuous and interrupted methods for episiotomy or perineal tears.\n A randomised controlled trial.\n The Hospital Universitario Principe de Asturias, a state hospital belonging to the community of Madrid.\n Four hundred forty-five women who had undergone vaginal deliveries with episiotomies or second-grade tearing of the perineum between September 2005 and July 2007.\n One group was repaired with continuous, nonlocking sutures involving the vagina, perineum, and subcutaneous tissues. The other group had continuous, locking sutures of the vagina, interrupted sutures in the perineal muscles, and interrupted transcutaneous sutures. The threads used for stitching were identical in both groups.\n The participants were questioned regarding the sensation of pain and the use of painkillers on the second and the tenth days, and 3 months postpartum.\n When comparing the group with continuous suture to the group with interrupted sutures, the differences included less repair time (1 minute; P= 0.017) and less suture material used (relative risk [RR], 3.2, 95% CI: 2.6-4.0). The comparison of pain on the second and tenth days, and 3 months postpartum were not statistically different between the two techniques (RR, 1.08, 95% CI: 0.74-1.57; RR, 0.96, 95% CI: 0.59-1.55; and RR, 0.68, 95% CI: 0.19-2.46, respectively).\n Although we did not demonstrate that one technique was better than the other in the incidence of pain in the short or long term, we showed that episiotomy and perineal tear repairs with continuous suturing were quicker and used less suture material without an increase in complication than interrupted suturing.", "nan", "Three methods of episiotomy repair were randomly assigned after 900 consecutive deliveries. The three procedures were: (1) continuous No. 00-plain catgut in the vagina; No. 00-plain catgut interrupted stitches in the perineal muscles and fascia, and No. 00-nylon interrupted stitches in the skin. (2) The same technique as in (1), but with No. 0-polyglycolic acid (Dexon) in all layers. (3) The suture material as in (2), but used with a subcuticular technique. The women treated with method 3 reported statistically significant less pain and disabilities in the early puerperium. Three months after delivery 262 women (33%) still had perineal complaints which could be directly related to the episiotomy in 25% (8% of total number). The group treated with method 3 had the best long-term results and we conclude that the subcuticular technique using polyglycolic acid should be the method of choice.", "To compare a continuous suture technique with interrupted stitches using inverted knots for postpartum perineal repair of second-degree lacerations and episiotomies.\n A double-blind randomised controlled trial.\n A Danish university hospital with more than 4800 deliveries annually.\n A total of 400 healthy primiparous women with a vaginal delivery at term. METHOD Randomisation was computer-controlled. Structured interviews and systematic assessment of perineal healing were performed by research midwives blinded to treatment allocation at 24-48 hours, 10 days and 6 months postpartum. Pain was evaluated using a visual analogue scale and the McGill Pain Questionnaire. Wound healing was evaluated using the REEDA scale and by assessment of gaping wounds >0.5 cm. Analysis complied with the intention-to-treat principle.\n The primary outcome was perineal pain 10 days after delivery. Secondary outcomes were wound healing, patient satisfaction, dyspareunia, need for resuturing, time elapsed during repair and amount of suture material used.\n A total of 400 women were randomised; 5 women withdrew their consent, leaving 395 for follow up. The follow-up rate was 98% for all assessments after delivery. No difference was seen in perineal pain 10 days after delivery. No difference was seen in wound healing, patient satisfaction, dyspareunia or need for resuturing. The continuous suture technique was significantly faster (15 versus 17 minutes, P = 0.03) and less suture material was used (one versus two packets, P < 0.01).\n Interrupted, inverted stitches for perineal repair leaving the skin unsutured appear to be equivalent to the continuous suture technique in relation to perineal pain, wound healing, patient satisfaction, dyspareunia and need for resuturing. The continuous technique, however, is faster and requires less suture material, thus leaving it the more cost-effective of the two techniques evaluated." ]

[ "15231556", "16153354", "1774421", "9626725", "15748090", "9862607", "11986508", "11560537", "15550800", "15107654" ]

[ "Cost-effectiveness of computerised cognitive-behavioural therapy for anxiety and depression in primary care: randomised controlled trial.", "A trial of problem-solving by community mental health nurses for anxiety, depression and life difficulties among general practice patients. The CPN-GP study.", "Life satisfaction and psychosocial functioning in chronic depression: effect of acute treatment with antidepressants.", "Impact of improved depression treatment in primary care on daily functioning and disability.", "Evaluation of the cost effectiveness of escitalopram versus venlafaxine XR in major depressive disorder.", "The treatment of chronic depression, part 3: psychosocial functioning before and after treatment with sertraline or imipramine.", "Psychodynamic psychotherapy and clomipramine in the treatment of major depression.", "Cost-effectiveness of practice-initiated quality improvement for depression: results of a randomized controlled trial.", "The effect of improving primary care depression management on employee absenteeism and productivity. A randomized trial.", "The cost-effectiveness of mirtazapine versus paroxetine in treating people with depression in primary care." ]

[ "Cognitive-behavioural therapy (CBT) is effective for treating anxiety and depression in primary care, but there is a shortage of therapists. Computer-delivered treatment may be a viable alternative.\n To assess the cost-effectiveness of computer-delivered CBT.\n A sample of people with depression or anxiety were randomised to usual care (n=128) or computer-delivered CBT (n=146). Costs were available for 123 and 138 participants, respectively. Costs and depression scores were combined using the net benefit approach.\n Service costs were 40 British pounds (90% CI - 28 British pounds to 148 British pounds) higher over 8 months for computer-delivered CBT. Lost-employment costs were 407 British pounds (90% CI 196 British pounds to 586 British pounds) less for this group. Valuing a 1-unit improvement on the Beck Depression Inventory at 40 British pounds, there is an 81% chance that computer-delivered CBT is cost-effective, and it revealed a highly competitive cost per quality-adjusted life year.\n Computer-delivered CBT has a high probability of being cost-effective, even if a modest value is placed on unit improvements in depression.", "To compare the effectiveness of community mental health nurse (CMHN) problem-solving and generic CMHN care, against usual general practitioner (GP) care in reducing symptoms, alleviating problems, and improving social functioning and quality of life for people living in the community with common mental disorders; and to undertake a cost comparison of each CMHN treatment compared with usual GP care.\n A pragmatic, randomised controlled trial with three arms: CMHN problem-solving, generic CMHN care and usual GP care.\n General practices in two southern English counties were included in the study. CMHNs were employed by local NHS trusts providing community mental health services.\n Participants were GP patients aged 18--65 years with a new episode of anxiety, depression or reaction to life difficulties and had to score at least 3 points on the General Health Questionnaire-12 screening tool. Symptoms had to be present for a minimum of 4 weeks but no longer than 6 months.\n Patients were randomised to one of three groups: (1) CMHN problem-solving treatment, (2) generic CMHN treatment, or (3) usual GP care. All three groups of patients remained free to consult their GPs throughout the course of the study, and could be prescribed psychotropic drug treatments.\n Patients were assessed at baseline, and 8 weeks and 26 weeks after randomisation. The primary outcome measure was psychological symptoms measured on the Clinical Interview Schedule -- Revised. Other measures included social functioning, health-related quality of life, problem severity and satisfaction. The economic outcomes were evaluated with a cost--utility analysis.\n Twenty-four CMHNs were trained to provide problem-solving under supervision, and another 29 were referred patients for generic support. In total, 247 patients were randomised to the three arms of the study, referred by 98 GPs in 62 practices. All three groups of patients were greatly improved by the 8-week follow-up. No significant differences were found between the groups at 8 weeks or 26 weeks in symptoms, social functioning or quality of life. Greater satisfaction with treatment was found in the CMHN groups. CMHN care represented a significant additional health service cost and there were no savings in sickness absence.\n The study found that specialist mental health nurse support is no better than support from GPs for patients with anxiety, depression and reactions to life difficulties. The results suggest that healthcare providers could consider adopting policies of restricting referrals of unselected patients with common mental disorders to specialist CMHNs, although there may be other roles in primary care that CMHNs could play effectively. Further research should address the predictors of chronicity in common mental disorders and target extra treatment. More research is also needed into the effectiveness and cost-effectiveness of problem-solving treatment for other disorders, of facilitated self-help treatments for common mental disorders and of CMHN care for people with severe and enduring mental illnesses, as well as the prevention of mental disorders.", "Social functioning was evaluated in 61 chronically depressed adults with early onset. Patients were treated for 6 weeks in a double-blind trial of phenelzine, imipramine, L-deprenyl, or placebo and functioning was reassessed. The posttreatment social functioning of patients who received drug treatment was superior to the placebo group in the following areas: work functioning, house functioning, relationship with relatives, sex frequency and life satisfaction. These results suggest that psychosocial impairment in some chronic depressives may be a sequaela of depression, rather than a global manifestation of characterological pathology.", "Few data are available regarding the impact of improved depression treatment on daily functioning and disability.\n In two studies of more intensive depression treatment in primary care, patients initiating antidepressant treatment were randomly assigned to either usual care or to a collaborative management programme including patient education, on-site mental health treatment, adjustment of antidepressant medication, behavioural activation and monitoring of medication adherence. Assessments at baseline as well as 4 and 7 months included several measures of impairment, daily functioning and disability: self-rated overall health, number of bodily pains, number of somatization symptoms, changes in work due to health, reduction in leisure activities due to health, number of disability days and number of restricted activity days.\n Average data from the 4- and 7-month assessments in both studies, intervention patients reported fewer somatic symptoms (OR 0.68, 95% CI 0.46, 0.99) and more favourable overall health (OR 0.50, 95% CI 0.28, 0.91). While intervention patients fared better on other measures of functional impairment and disability, none of these differences reached statistical significance.\n More effective acute-phase depression treatment reduced somatic distress and improved self-rated overall health. The absence of a significant intervention effect on other disability measures may reflect the brief treatment and follow-up period and the influence of other individual and environmental factors on disability.", "To assess the relative cost effectiveness of escitalopram compared with venlafaxine XR in patients with major depressive disorder (MDD).\n An economic evaluation was conducted alongside a double-blind, multinational, randomised clinical trial and examined the costs and quality of life of 251 patients taking escitalopram versus venlafaxine. Outpatients fulfilling criteria for MDD were randomised to receive oral escitalopram 10-20 mg/day or venlafaxine 75-150 mg/day for 8 weeks. Patient-reported outcomes (EuroQOL questionnaire, Quality of Life Depression Scale), use of medical services and absence from work (relating to the previous 3 months) were recorded at baseline, with repeated measurements at week 8. Unit costs in year values were applied to the resource utilisation data. A cost-effectiveness analysis was performed using the EuroQOL score as the effectiveness measure. The perspective was that of the healthcare payer, with a societal perspective considered in a sensitivity analysis.\n Statistically significant improvements in patient-reported outcomes (vs baseline) were observed in both groups after 8 weeks' treatment. Patients treated with escitalopram tended to report fewer problems on the EuroQOL dimensions than venlafaxine recipients. Mean per-patient costs in euros (euro, year 2003 values) for the escitalopram group, compared with the venlafaxine group, were 32% lower (110 euros vs 161euros) from a healthcare perspective, although this was not a statistically significant difference. Differences were related to lower drug acquisition costs and fewer hospitalisations for escitalopram than venlafaxine recipients. A multivariate model adjusting for baseline characteristics showed that escitalopram reduced direct costs compared with venlafaxine (p = 0.007). Bootstrapped distributions of the incremental cost-effectiveness ratios also showed similar effectiveness but lower costs for escitalopram compared with venlafaxine. Inclusion of indirect costs led to similar results.\n This prospective economic analysis suggests that escitalopram has similar effectiveness to venlafaxine in the treatment of MDD, but may be associated with lower healthcare costs. These findings are consistent with previously published economic evaluations.", "Previous research has suggested that depressed patients, and particularly chronically depressed patients, have significant impairments in many areas of their lives. While previous studies suggested that these \"psychosocial\" impairments improve following pharmacologic treatment, no large scale definitive study using multiple measures of psychosocial functioning has been reported.\n We assessed multiple domains of psychosocial functioning using interviewer-rated and self-report measures within the context of a 12-week acute treatment trial of sertraline and imipramine for patients with chronic depression (double depression and chronic major depression). We also compared the psychosocial functioning data of this sample before and after treatment with normative data available from published community samples.\n Chronically depressed patients manifested severe impairments in psychosocial functioning at baseline. After treatment with sertraline or imipramine, psychosocial functioning improved significantly. Significant improvements appeared relatively early in treatment (week 4). Despite these highly significant improvements in functioning during acute treatment, the study sample as a whole did not achieve levels of psychosocial functioning comparable to a comparator nondepressed community sample. However, patients who reached full symptomatic response (remission) during acute treatment did have levels of psychosocial functioning in most areas at endpoint that approached or equaled those of community samples.\n These results indicate that successful antidepressant treatment with sertraline or imipramine can alleviate the severe psychosocial impairments found in chronic depression.", "The authors compared a combination of clomipramine and psychodynamic psychotherapy with clomipramine alone in a randomized controlled trial among patients with major depression.\n Seventy-four patients between the ages of 20 and 65 years who were assigned to ten weeks of acute outpatient treatment for major depression were studied. Bipolar disorder, psychotic symptoms, severe substance dependence, organic disorder, past intolerance to clomipramine, and mental retardation were exclusion criteria.\n Marked improvement was noted in both treatment groups. Combined treatment was associated with less treatment failure and better work adjustment at ten weeks and with better global functioning and lower hospitalization rates at discharge. A cost savings of 2,311 dollars per patient in the combined treatment group, associated with lower rates of hospitalization and fewer lost work days, exceeded the expenditures related to providing psychotherapy.\n Provision of supplemental psychodynamic psychotherapy to patients with major depression who are receiving antidepressant medication is cost-effective.", "Depression is a leading cause of disability worldwide, but treatment rates in primary care are low.\n To determine the cost-effectiveness from a societal perspective of 2 quality improvement (QI) interventions to improve treatment of depression in primary care and their effects on patient employment.\n Group-level randomized controlled trial conducted June 1996 to July 1999.\n Forty-six primary care clinics in 6 community-based managed care organizations.\n One hundred eighty-one primary care clinicians and 1356 patients with positive screening results for current depression.\n Matched practices were randomly assigned to provide usual care (n = 443 patients) or to 1 of 2 QI interventions offering training to practice leaders and nurses, enhanced educational and assessment resources, and either nurses for medication follow-up (QI-meds; n = 424 patients) or trained local psychotherapists (QI-therapy; n = 489). Practices could flexibly implement the interventions, which did not assign type of treatment.\n Total health care costs, costs per quality-adjusted life-year (QALY), days with depression burden, and employment over 24 months, compared between usual care and the 2 interventions.\n Relative to usual care, average health care costs increased $419 (11%) in QI-meds (P =.35) and $485 (13%) in QI-therapy (P =.28); estimated costs per QALY gained were between $15 331 and $36 467 for QI-meds and $9478 and $21 478 for QI-therapy; and patients had 25 (P =.19) and 47 (P =.01) fewer days with depression burden and were employed 17.9 (P =.07) and 20.9 (P =.03) more days during the study period.\n Societal cost-effectiveness of practice-initiated QI efforts for depression is comparable with that of accepted medical interventions. The intervention effects on employment may be of particular interest to employers and other stakeholders.", "To test whether an intervention to improve primary care depression management significantly improves productivity at work and absenteeism over 2 years.\n Twelve community primary care practices recruiting depressed primary care patients identified in a previsit screening.\n Practices were stratified by depression treatment patterns before randomization to enhanced or usual care. After delivering brief training, enhanced care clinicians provided improved depression management over 24 months. The research team evaluated productivity and absenteeism at baseline, 6, 12, 18, and 24 months in 326 patients who reported full-or part-time work at one or more completed waves.\n Employed patients in the enhanced care condition reported 6.1% greater productivity and 22.8% less absenteeism over 2 years. Consistent with its impact on depression severity and emotional role functioning, intervention effects were more observable in consistently employed subjects where the intervention improved productivity by 8.2% over 2 years at an estimated annual value of US 1982 dollars per depressed full-time equivalent and reduced absenteeism by 28.4% or 12.3 days over 2 years at an estimated annual value of US 619 dollars per depressed full-time equivalent.\n This trial, which is the first to our knowledge to demonstrate that improving the quality of care for any chronic disease has positive consequences for productivity and absenteeism, encourages formal cost-benefit research to assess the potential return-on-investment employers of stable workforces can realize from using their purchasing power to encourage better depression treatment for their employees.", "Currently, there are no data available comparing cost-effectiveness of two antidepressants in the primary care setting in the UK. Alongside a randomized, double-blind, 24-week study of mirtazapine and paroxetine, data were prospectively collected on patients' use of hospital and non-hospital services and days off work. Costs were estimated in each treatment arm from National Health Service (NHS) and societal perspectives, and were compared with selected outcome measures (numbers of 17-item Hamilton Rating Scale for Depression (17-HAMD) responders and changes in Quality of Life in Depression Scale scores between baseline and 24-week endpoint) to explore and compare relative cost-effectiveness. Mirtazapine treatment resulted in a statistically significantly greater improvement in quality of life than paroxetine at endpoint (P=0.021). Although the 17-HAMD response rates were higher for the mirtazapine users at endpoint, the difference (7%) was not statistically significant (P=0.31). However, mean total societal costs per patient were 375 pounds less with mirtazapine (1850 pounds) compared to paroxetine (2225 pounds; P=0.32). Mean total NHS costs per patient were also lower (120 pounds) with mirtazapine (1408 pounds) compared to paroxetine (1528 pounds). The advantage for mirtazapine remained present on all variables analysed after performing sensitivity analyses. The results suggest that mirtazapine may be a cost-effective treatment choice compared to paroxetine for depression in a primary care setting." ]

[ "12188468", "15376781", "20599311" ]

[ "Impact of improvement of water supply on household economy in a squatter area of Manila.", "Environmental interventions and the pattern of geohelminth infections in Salvador, Brazil.", "Improved health outcomes in urban slums through infrastructure upgrading." ]

[ "To estimate the impact of the improvement of water supply. a comparative study on water collection and household expenditure on water was conducted between a former squatter community with an improved water supply (Leveriza: LE) and a typical squatter community with public water faucets (Maestranza: MA) in Manila, the Philippines. Data were collected from 201 structured household interviews and a focus group discussion among housewives in each community. To measure the time spent collecting water, observations of private and public water faucets were conducted. The residents in LE enjoyed significantly larger quantities of water from private water connections than in MA, where only three public water faucets were available as a water source. Conversely, the unit price of water in LE was much lower than in MA. In LE, 72.1% of the households started working for more income using time saved through the improvement of water supply and the proportion of the households under the poverty threshold was reduced from 55.6% to 29.9%. In MA, 68.6% of the households expressed their willingness to work for more income when time spent collecting water was saved. It would be possible for MA to reduce the proportion of the households under the poverty threshold through the improvement of the water supply. The results of the study indicated that the improvement of water supply would possibly encourage urban slum residents to increase their household incomes through reallocating time saved to income-generating activities. The underserved residents spent more money for less water compared to those with access to private water connections. In MA, it took 3-4 h, on average, to complete one water collecting task, even though the nearest public water faucet was within 100 m of any housing unit. This suggests that the definition of accessibility to safe water be reconsidered when discussing the urban poor.", "This paper reports a longitudinal study, conducted in 1989/90, of 1893 children aged 5 to 14 years in 9 poor urban areas of the city of Salvador (population 2.44 million), capital of Bahia State in northeast Brazil. Stool examinations were performed to measure nematode infection and reinfection 9 months after treatment, and an extensive questionnaire was applied to collect information on each child and on the conditions of the household. Comparison of areas with different levels of infrastructure showed the following trends as the level of community sanitation improved: clustering of cases by household became more significant, predisposition of individuals to reinfection and to heavy infection became more marked, and infections with different species were increasingly aggregated in the same individuals. These results suggest that sewerage and drainage can significantly reduce transmission of intestinal nematode infections in the public domain, but that other measures are required to control transmission within the household.", "The world is rapidly urbanizing with over half the population now living in urban areas. As the urban population grows, so does the proportion of these persons living in slums where conditions are deplorable. These conditions concentrate health hazards leading to higher rates of morbidity and mortality. This growing problem creates a unique challenge for policymakers and public health practitioners. While the Millennium Development Goals (MDGs) aim to address these conditions and standards for water and sanitation as well as pertinent health outcomes, little evidence on interventions exists to guide policymakers. Upgrades in slum household water and sanitation systems have not yet been rigorously evaluated to demonstrate whether there is a direct link to improved health outcomes. This study aims to show that slum upgrading as carried out in Ahmedabad, India, led to a significant decline in waterborne illness incidence. We employ a quasi-experimental regression model using health insurance claims (for 2001-2008) as a proxy for passive surveillance of disease incidence. We found that slum upgrading reduced a claimant's likelihood of claiming for waterborne illness from 32% to 14% and from 25% to 10% excluding mosquito-related illnesses. This study shows that upgrades in slum household infrastructure can lead to improved health outcomes and help achieve the MDGs. It also provides guidance on how upgrading in this context using microfinance and a public-private partnership can provide an avenue to affect positive change.\n Copyright (c) 2010 Elsevier Ltd. All rights reserved." ]

[ "20607003", "19568761", "20070722" ]

[ "Does local endometrial injury in the nontransfer cycle improve the IVF-ET outcome in the subsequent cycle in patients with previous unsuccessful IVF? A randomized controlled pilot study.", "Local injury to the endometrium on the day of oocyte retrieval has a negative impact on implantation in assisted reproductive cycles: a randomized controlled trial.", "Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation/intra cytoplasmic sperm injection: a randomised clinical trial." ]

[ "Management of repeated implantation failure despite transfer of good-quality embryos still remains a dilemma for ART specialists. Scrapping of endometrium in the nontransfer cycle has been shown to improve the pregnancy rate in the subsequent IVF/ET cycle in recent studies.\n The objective of this randomized controlled trial (RCT) was to determine whether endometrial injury caused by Pipelle sampling in the nontransfer cycle could improve the probability of pregnancy in the subsequent IVF cycle in patients who had previous failed IVF outcome.\n Tertiary assisted conception center.\n Randomized controlled study.\n 100 eligible patients with previous failed IVF despite transfer of good-quality embryos were randomly allocated to the intervention group and control groups. In the intervention group, Pipelle endometrial sampling was done twice: One in the follicular phase and again in the luteal phase in the cycle preceding the embryo transfer cycle.\n The primary outcome measure was live birth rate. The secondary outcome measures were implantation and clinical pregnancy rates.\n The live birth rate was significantly higher in the intervention group compared to control group (22.4% and 9.8% P = 0.04). The clinical pregnancy rate in the intervention group was 32.7%, while that in the control group was 13.7%, which was also statistically significant (P = 0.01). The implantation rate was significantly higher in the intervention group as compared to controls (13.07% vs 7.1% P = 0.04).\n Endometrial injury in nontransfer cycle improves the live birth rate, clinical pregnancy and implantation rates in the subsequent IVF-ET cycle in patients with previous unsuccessful IVF cycles.", "To evaluate the effect of local injury to the endometrium on the day of oocyte retrieval on implantation and pregnancy rates in assisted reproductive cycles.\n In a prospective controlled trial, a total of 156 patients, <38 years old, in their first in vitro fertilization (IVF) cycle were randomized. In 77 patients, two small endometrial samples from anterior and posterior walls of uterus were obtained with a Novak curette on the day of oocyte retrieval and in 79 patients no intervention was performed.\n The experimental and control patients were matched regarding women's age, body mass index, basal FSH, duration and etiology of infertility, treatment protocol, number of retrieved oocyte, endometrial thickness, percentage of intracytoplasmic sperm injection performance, fertilization rate, the percentage of patients with good and top quality embryos, and the number of embryos transferred. The implantation rate (7.9 vs. 22.9%), clinical (12.3 vs. 32.9%; odds ratio = 0.25; 95% confidence interval = 0.12-0.66; p < 0.05) and ongoing pregnancy (9.6 vs. 29.1%; odds ratio = 0.25; 95% confidence interval = 0.10-0.64; p < 0.05) rates were significantly lower in experimental group, compared with 79 controls.\n According to the results of this study, local injury to the endometrium on the day of oocyte retrieval disrupts the receptive endometrium and has a negative impact on implantation and IVF outcomes.", "Implantation failure is the most important cause of recurrent in vitro fertilisation (IVF)/intra cytoplasmic sperm injection (ICSI) failure. It has been reported that endometrial injury using a biopsy catheter resulted in a higher pregnancy rate in following cycle of treatment. The local endometrial trauma increases the implantation rate through the release of chemical mediators such as histamine and growth factor.\n To evaluate the influence of endometrial biopsy on increasing implantation rate in patients with recurrent implantation failures.\n In a randomised control trial study, 115 women each with at least two implantation failures were randomly assigned to two groups. In the case group, endometrial biopsy was obtained from patients in the luteal phase of previous cycle, and implantation and clinical pregnancy rates were compared with those of patients in the control group.\n The implantation rate was determined as 10.9% in the biopsy group compared to 3.38% in the controls. The clinical pregnancy rate was significantly higher in the case group than in controls (27.1% and 8.9% respectively).\n The results suggest that pregnancy outcome increases through IVF or ICSI after endometrial biopsy." ]

[ "3310826", "11704167", "11535207", "2178992", "8749599", "11672550", "10494484", "10906499", "15722066", "9853201", "7621685", "7796587", "8213103", "4105854", "8838483", "9773261", "10717778", "9115000", "11704101", "11535206", "10036600", "8934063", "18161401", "8222651", "18580398", "5508499", "2596365", "8689882", "16763008", "15932834", "8629458", "8842582", "11257242", "9098463", "7775629", "10923282", "4208342", "11929644", "16542051", "8137624", "20185226", "908899" ]

[ "Blood glucose, serum insulin, serum growth hormone and serum glycosylated proteins during two years' oral contraception with low-estrogen combinations.", "Menstrual reduction with extended use of combination oral contraceptive pills: randomized controlled trial.", "Effects of two low-dose oral contraceptives containing ethinylestradiol and either desogestrel or levonorgestrel on serum lipids and lipoproteins with particular regard to LDL size.", "A double-blind comparison of the efficacy and acceptability of Femodene and Microgynon-30.", "Ovarian activity suppression by two different low-dose triphasic oral contraceptives.", "Weight change and adverse event incidence with a low-dose oral contraceptive: two randomized, placebo-controlled trials.", "A comparative study of two contraceptive vaginal rings releasing norethindrone acetate and differing doses of ethinyl estradiol.", "Efficacy, cycle control, and safety of two triphasic oral contraceptives: Cyclessa (desogestrel/ethinyl estradiol) and ortho-Novum 7/7/7 (norethindrone/ethinyl estradiol): a randomized clinical trial.", "Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial.", "Efficacy and acceptability of two monophasic oral contraceptives containing ethinylestradiol and either desogestrel or gestodene.", "A multicentred phase III comparative clinical trial of Mesigyna, Cyclofem and Injectable No. 1 given monthly by intramuscular injection to Chinese women. I. Contraceptive efficacy and sid effects.", "Multicenter trial of two monophasic oral contraceptives containing 30 mcg ethinylestradiol and either desogestrel or gestodene in Thai women.", "Effect of norethisterone and levonorgestrel in low-dose multiphasic oral contraceptives on serum lipids.", "A placebo-controlled double-blind crossover investigation of the side effects attributed to oral contraceptives.", "A comparative study of the effects of the hemostatic system of two monophasic gestodene oral contraceptives containing 20 micrograms and 30 micrograms ethinylestradiol.", "A randomized cross-over study on various hormonal parameters of two triphasic oral contraceptives.", "Comparison of efficacy, cycle control, and tolerability of two low-dose oral contraceptives in a multicenter clinical study.", "A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 30 micrograms ethinylestradiol/75 micrograms gestodene, with respect to efficacy, cycle control, and tolerance.", "Open, multicenter comparison of efficacy, cycle control, and tolerability of a 23-day oral contraceptive regimen with 20 microg ethinyl estradiol and 75 microg gestodene and a 21-day regimen with 20 microg ethinyl estradiol and 150 microg desogestrel.", "Multicenter, comparative study of cycle control, efficacy and tolerability of two low-dose oral contraceptives containing 20 microg ethinylestradiol/100 microg levonorgestrel and 20 microg ethinylestradiol/500 microg norethisterone.", "A comparison of the cycle control and tolerability of two ultra low-dose oral contraceptives containing 20 micrograms ethinylestradiol and either 150 micrograms desogestrel or 75 micrograms gestodene.", "Investigation of the influence of two low-dose monophasic oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 30 micrograms ethinylestradiol/75 micrograms gestodene, on lipid metabolism in an open randomized trial.", "Effects of low-dose oral contraceptives on body weight: results of a randomized study of up to 13 cycles of use.", "Long-interval treatment regimen with a desogestrel-containing oral contraceptive.", "Effect of oral contraceptives on weight and body composition in young female runners.", "The development of elevated blood pressure while using oral contraceptives: a preliminary report of a prospective study.", "A study comparing a gestoden triphasic formulation with a fixed combination OC.", "Changes in androgens during treatment with four low-dose contraceptives.", "Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 microg ethinyl estradiol and 3 mg drospirenone.", "Extended use of transdermal norelgestromin/ethinyl estradiol: a randomized trial.", "The influence of the dose of ethinylestradiol in oral contraceptives on follicle growth.", "Shorter pill-free interval in combined oral contraceptives decreases follicular development.", "Comparison of the lipoprotein, carbohydrate, and hemostatic effects of phasic oral contraceptives containing desogestrel or levonorgestrel.", "Evaluation of body composition during low-dose estrogen oral contraceptives treatment.", "Effects of a new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the renin-aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism.", "Effect of an oral contraceptive containing drospirenone on the renin-angiotensin-aldosterone system in healthy female volunteers.", "A double-blind comparison of two oral contraceptives containing 50 mu g. and 30 mu g. ethinyl estradiol.", "Effect of dienogest-containing oral contraceptives on lipid metabolism.", "A comparison of the cycle control, safety, and efficacy profile of a 21-day regimen of ethinylestradiol 20mug and drospirenone 3mg with a 21-day regimen of ethinylestradiol 20mug and desogestrel 150mug.", "Clinical comparison of two low-dose oral contraceptives, Minulet and Mercilon, in women over 30 years of age.", "A comparison between monophasic levonorgestrel-ethinyl estradiol 150/30 and triphasic levonorgestrel-ethinyl estradiol 50-75-125/30-40-30 contraceptive pills for side effects and patient satisfaction: a study in Iran.", "Comparative clinical trial of two oral contraceptives with a low--estrogen content." ]

[ "Body weight, fasting blood glucose (GP) (BFG), serum immunoreactive insulin (IRI), serum growth hormone (GH) and serum glycosylated proteins were longitudinally followed in 2 groups of women during two years' oral contraception. One group (n = 10) received a combination of 0.030 mg ethinylestradiol and 0.150 mg levonorgestrel and the other (n = 10) a combination of 0.030 mg ethinylestradiol and 0.150 mg of desogestrel. There was a significant increase in BFG during the study and the values were still rising, when examined 2 months after discontinuation of the pill. Two subjects, reaching the level of 5.5 mmol/l showed normal pretreatment values, when investigated one year later. After 6 months' use of either preparation, GH significantly increased, remained on that level throughout the study and returned to the pretreatment level after discontinuation of the pill. Body weight, IRI and GPP did not change significantly during the study.", "To compare a traditional 28-day cycle to an extended 49-day cycle of the 30 microg ethinyl estradiol (E2)/300 microg norgestrel monophasic birth control pill regimen.\n Ninety subjects randomized to either 28-day cycles with 21 active pills or 49-day cycles with 42 active pills for a prospective open label trial over four 84-day reference periods or trimesters. Bleeding, pill taking, and symptom diaries were completed. The sample size with 80% power to detect a 40% reduction in bleeding days required 24 subjects in each arm.\n Of the 90 women, 24 subjects (54.5%) on the 28-day cycle and 29 (63%) on the 49-day cycle completed the entire study (P =.41). There were no statistically significant differences between the two groups in demographics or continuation rates. There was a significant reduction in bleeding days in the experimental arm beginning in the first trimester (28-day = 10.9, 49-day = 6.4 mean days of bleeding, P <.001) and continuing to the fourth trimester (28-day = 11.3, 49-day = 5.8 mean days, P =.005). The number of spotting days was similar between both schedules in the first trimester (28-day = 4.8, 49-day = 3.7 mean days, P =.24) and continued into the fourth trimester (28-day = 3.4, 49-day = 2.9 mean days, P =.30). Annual expenditure for hygiene products was significantly less for extended use subjects (28-day = $41.45, 49-day = $17.54 spent, P <.001).\n Extension of the 28-day oral contraceptive (OC) cycle to a 49-day cycle resulted in fewer bleeding days and no increase in mean spotting days or bleeding episodes.", "This study was designed to determine the effects of two low-dose oral contraceptives, most frequently given in our area, monophasic desogestrel/ethinylestradiol (DG/EE) and triphasic levonorgestrel/ethinylestradiol (LNG/EE), on lipoprotein parameters, especially LDL particle size and HDL subclass distribution (determined by lipid-stained 2%-20% polyacrylamide gradient gel electrophoresis) in 37 healthy normolipidemic women aged 19 to 27 years. Lipid and lipoprotein parameters were measured before the start of treatment and in the third month of oral contraceptive use. Results reflected the estrogen-progestin balance. As compared with baseline values, with both formulations, plasma total cholesterol, phospholipids, and HDL3 cholesterol increased, and LDL-predominant peak size decreased, with a translation of LDL pattern A towards pattern I. With DG/EE, plasma triglycerides, apolipoproteins AI and B increased. With LNG/EE, LDL cholesterol increased, and HDL2 cholesterol decreased. All these modifications were moderate, within threshold limits. Estrogen-dominant monophasic DG/EE appears to be more favorable than progestin-dominant triphasic LNG/EE, since the reduction in LDL-predominant peak size is not associated with an increase in LDL cholesterol or with a decrease in HDL2 cholesterol.", "The efficacy, cycle-control and tolerance of Microgynon-30, a widely prescribed levonorgestrel containing oral contraceptive, and Femodene, a new oral-contraceptive containing gestodene, were compared in a randomised, double-blind study involving 456 healthy women over a 6 month period. 229 women were allocated to receive Femodene and 227 received Microgynon-30. No differences between the groups in terms of obstetric and gynaecological history, previous contraceptive history, smoking habits, blood-pressure or body weight at admission were observed. No pregnancies were reported in either group, despite tablet-taking errors recorded in 6.3% of the Femodene group and 7.6% of the Microgynon-30 group. Both oral contraceptives were compared in terms of cycle length, intensity of the withdrawal bleed and side effects. Cycle-control was similar in the two groups. However, significantly fewer subjects reported breakthrough bleeding (with or without spotting) in the Femodene group (18% of patients) compared with the Microgynon-30 group (26% of patients). The incidence of absent withdrawal bleeds was 1% or less in both groups and no significant effects on body weight or blood pressure were observed.", "In an open, randomized study in an outpatient clinic of a large teaching hospital, thirty-one female volunteers with regular cycles and established ovulation by ultrasonography were given one of two triphasic oral contraceptives containing ethinylestradiol combined with levonorgestrel or desogestrel during six cycles of treatment. The main outcome measures were transvaginal ultrasonography and serum E2 and P measurements in pill cycles 1, 3 and 6. No ovarian activity was found in 10 subjects. Among the remaining 21 women who showed ovarian activity, most follicle-like structures developed in the pill-free week and decreased in size or disappeared in the first pill week. One women taking triphasic desogestrel had evidence of a luteinized unruptured follicle and one women taking triphasic levonorgestrel had a possible ovulation. The latter women also showed symptoms of lower abdominal pain. A statistically significant difference in ovarian activity between the two oral contraceptives could not be established. The two triphasic oral contraceptives suppressed ovarian activity to the same degree. A trend was seen towards increasing ovarian activity with duration of use in both treatment groups.", "Changes in body weight and the incidence of estrogen-related side effects with low-dose oral contraceptives (OCs) containing 20 microg ethinyl estradiol (EE) have not been demonstrated in placebo-controlled trials. Two placebo-controlled, randomized trials demonstrated the efficacy of a low-dose OC for the treatment of acne in healthy females (n = 704; >or=14 years old) with regular menstrual cycles and moderate facial acne. Patients were randomized to receive 20 microg EE/100 microg levonorgestrel (LNG) or placebo for six cycles. Body weight was measured at baseline and during Cycles 1, 3, and 6. The occurrence of adverse events was recorded at each visit. Mean changes in weight from baseline were similar with 20 microg EE/100 microg LNG [0.72 kg +/- 2.64 (SD; n = 349)] and placebo [0.56 kg +/- 2.64 (SD; n = 355; p > 0.05)] for the last measured weight of each patient. Rates of headache, nausea, weight gain, and breast pain, side effects commonly attributed to OCs, were also similar between groups (p > 0.05). No serious, unexpected, drug-related adverse events occurred during the study. The low-dose OC containing 20 microg EE/100 microg LNG is safe, well tolerated, and does not cause weight gain.", "Two combined contraceptive vaginal rings (CVR) each releasing approximately 1 mg norethindrone acetate (NET-Ac) and either 20 micrograms or 15 micrograms ethinyl estradiol over 24 h were tested at three clinic sites in Los Angeles, San Francisco, and Sydney. A total of 61 women were enrolled to use the ring on a schedule of 3 weeks in/1 week out for four treatment cycles. Serum estradiol, progesterone, norethindrone (NET), and ethinyl estradiol (EE) levels were assayed twice weekly in all four treatment cycles. Both CVR performed well, with no pregnancies occurring and only one cycle of luteal activity suggestive of ovulation (serum progesterone > 32 nmol/L) occurring with each ring (0.9% of cycles with the 1/15 ring and 1.2% of cycles with the 1/20 ring). Although there was significantly more luteal activity in women using the 1/15 CVR (5.9% compared with 1.2% of cycles), only three cycles with a marked degree of luteal activity (progesterone > 10 nmol/L) occurred among compliant women. Serum levels of NET and EE were consistently elevated during use of both rings. There was no significant difference between serum levels with the two rings because of wide interindividual variations, although both NET and EE levels tended to be higher with the 1/20 ring. However, there was a significant difference in EE levels between the women in Los Angeles and Sydney using the same dose rings. Total cholesterol, HDL, and LDL cholesterol values were not significantly changed during treatment. Triglycerides increased but remained within the normal range. Overall cycle control was good with both formulations, but there was slightly more cycle disturbance with the lower dose ring. There was no change in mean body weight during the study, and individual weight changes appeared to be idiosyncratic. Side effects were infrequent and similar to those reported with other steroidal contraceptive methods. Three women complained of vaginal discharge, one with accompanying itch and one with a vaginal Candida infection in cycle 1. Overall, both of these EE/NET-Ac rings performed well, with only minor and mainly nonsignificant differences in effect on serum EE, NET, E2, and progesterone levels and lipids, and on vaginal bleeding patterns.", "The contraceptive efficacy, cycle control, and safety of a new low-dose, triphasic desogestrel/ethinyl estradiol oral contraceptive (CTR 77, Cyclessa(TM)) was compared to that of a marketed, triphasic norethindrone/ethinyl estradiol oral contraceptive (Ortho-Novum(R) 7/7/7). Two identical multicenter, open-label, randomized, parallel group, comparative Phase III 6-cycle trials were designed to each enroll 4200 healthy women. The combined comparative data for Cyclessa versus Ortho-Novum 7/7/7 for both studies are reported here. Cyclessa and Ortho-Novum 7/7/7 had comparable contraceptive efficacy. Despite a lower ethinyl estradiol dose (25 microg/day vs. 35 microg/day), the Cyclessa group had significantly improved cycle control in comparison to the Ortho-Novum 7/7/7 group for presence of a withdrawal bleed (p = 0.001), lack of early withdrawal bleed (p = 0.01), and breakthrough bleeding/spotting (p = 0.001). For each of the months of the study, the incidence of breakthrough bleeding/spotting was lower in the Cyclessa group than the Ortho-Novum 7/7/7 group (breakthrough bleeding, p = 0.006; breakthrough spotting, p = 0.001). The incidence of other adverse events was similar among treatment groups, an observation that supports the safety of both formulations. There was significantly less weight gain (p = 0.0002) and less increase in the body mass index (BMI) (p = 0.0002) in the Cyclessa group. The contraceptive efficacy and safety of Cyclessa is comparable to Ortho-Novum 7/7/7. Cyclessa provides significantly improved cycle control with no weight gain.", "This open-label, randomized, Phase III study compared the efficacy and tolerability of and compliance with NuvaRing, a combined contraceptive vaginal ring releasing 15 microg of ethinylestradiol (EE) and 120 microg of etonogestrel daily, with those of and with a combined oral contraceptive (COC) containing 150 microg of levonorgestrel (LNG) and 30 microg of EE. Subjects received NuvaRing or a COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-/pill-free period). A total of 1030 subjects (NuvaRing, n=512; COC, n=518) was randomized and started treatment (intent-to-treat [ITT] population). The percentage of women in the ITT population who completed the trial was 70.9% for the NuvaRing group and 71.2% for the COC group. Five in-treatment pregnancies occurred in each group, giving Pearl indices of 1.23 for NuvaRing and 1.19 for the COC. Compliance with both treatments was excellent and both were well tolerated. In conclusion, NuvaRing has comparable efficacy and tolerability with a COC containing 150 microg of LNG and 30 microg of EE and does not require daily dosing.", "To assess the contraceptive efficacy, cycle control and acceptability of two monophasic oral contraceptives containing either 30 micrograms ethinylestradiol plus 150 micrograms desogestrel or 30 micrograms ethinylestradiol plus 75 micrograms gestodene.\n In a randomized, open-label, six-cycle, group-comparative, multicenter study performed in Brazil, pregnancies, cycle-control parameters, incidence of side-effects and the presence and severity of acne vulgaris were assessed, and blood pressure and body weight were measured at pretreatment and after one, three and six cycles of oral contraceptive use.\n Of the 595 women enrolled, 274 (86.7%) in the desogestrel/ethinylestradiol group and 227 (81.4%) in the gestodene/ethinylestradiol group completed the six cycles, providing data for 1753 and 1487 treatment cycles, respectively. Two pregnancies occurred, one of which (in the desogestrel/ethinylestradiol group) was attributed to user failure, whilst the other (in the gestodene/ethinylestradiol group) was thought to result from method failure. Cycle control was observed to be excellent; the incidences of irregular bleeding and minor side-effects were low in both groups and decreased after an initial increase in the first cycle. Pre-existing acne improved in both groups, whereas blood pressure and body weight remained essentially unchanged.\n Both desogestrel/ethinylestradiol and gestodene/ethinylestradiol provide effective oral contraception with comparable cycle control and acceptability.", "A phase III clinical study was carried out among 5680 fertile Chinese women to evaluate efficacy and side effects of three monthly injectable contraceptives: Mesigyna, Cyclofem and Chinese Injectable No. 1. When used in a once-a-month treatment schedule (part 1 of study), the effectiveness of Chinese Injectable No. 1 was unacceptably low; 36 pregnancies occurred during the first 1743 women-months of use, 16 before the second injection. The study was restarted with a revised injection schedule for Injectable No. 1: two injections separated by 9 +/- 1 days during the first month and subsequent injections given 10-12 days after the onset of bleeding, or if no bleeding occurred, 28 days after previous injection. In part 2 of the study, 988, 990 and 992 subjects were provided Mesigyna, Cyclofem and Injectable No. 1, respectively. Life-table pregnancy rates at one year were 0.41%, 0% and 0.77% (p < 0.05), respectively; the overall discontinuation rates at one year were 13.9%, 19.1% and 20.4% (p < 0.001). Discontinuation rates for bleeding problems were significantly different between the groups: discontinuation rates for amenorrhea were 0.58%, 3.71% and 0.68% (p < 0.001) for Mesigyna, Cyclofem and Injectable No. 1; for other bleeding problems, the rates were 4.88%, 8.38% and 12.64% (p < 0.001). There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons. Mean weight changes after one year of use were small: 0.73, 0.86 and 0.17 kg for the three groups, respectively. Both Mesigyna and Cyclofem were very effective for contraception, but Mesigyna appeared to be tolerated slightly better with regard to cycle control; the modified dose regimen for Injectable No. 1 also gave a low pregnancy rate but was associated with higher rates of discontinuation.", "The efficacy and acceptability of two third generation oral contraceptives in Thai women were evaluated in a prospective, open, group-comparative, randomized, multicenter trial of women asking for contraception. In six Family Planning Centers and Outpatient Gynaecological Clinics in urban areas in Thailand, 783 healthy women who were at risk for pregnancy and did not have contraindications to oral contraceptive use were randomly allocated to one of the two study groups. An oral contraceptive containing 30 mcg ethinylestradiol and 150 mcg desogestrel was given to 394 women and an oral contraceptive with the same amount of ethinylestradiol and 75 mcg gestodene to 389 women during 6 cycles. Criteria of cycle control, side effects and the presence and severity of acne vulgaris were assessed and blood pressure and body weight measured at pretreatment and after cycles 1, 3 and 6. Furthermore, the efficacy was evaluated after the last cycle. No pregnancies occurred with either of the contraceptives. The incidences of irregular bleeding and minor side effects in both groups were very low and decreased after an initial increase in the first cycle. Acne improved in both groups. Blood pressure and body weight remained unchanged. The two oral contraceptives were found to be effective and acceptable in Thai women. Compared to Caucasian women, the incidences of irregular bleeding and side effects were apparently lower in these Asian women. Furthermore, the effects of both oral contraceptives were comparable.", "In a parallel, multicenter study in Norway and Finland involving a total of 196 healthy women (mean age 22.4 years, range 18-30), the effects on serum lipids and lipoproteins of two multiphasic oral contraceptives containing ethinyl estradiol (EE) but different progestins were examined. One formulation contained EE 35 micrograms and norethisterone (NET) 0.5 mg on days 1-7 and days 17-21 and elevated NET 1.0 mg during the midphase (days 8-16). The other formulation contained EE 30 micrograms on days 1-6 and days 12-21 and 40 micrograms on days 7-11 and phased levonorgestrel (LGN): 50 micrograms (days 1-6), 75 micrograms (days 7-11) and 125 micrograms (days 12-21). Both formulations induced significant elevation of total cholesterol (6.7 and 4.1%), Apo B (8.1 and 7.0%) as well as HDL (6.4 and 3.7%) for the EE/NET and EE/LGN formulation respectively. Mean serum levels of triglycerides were significantly elevated (58 and 47%). However, all mean serum lipid and lipoprotein values remained within the normal range, and no change in the calculated cholesterol ratio (HDL/total cholesterol) nor lipoprotein ratio (HDL/(HDL+LDL)) was observed. No significant difference between the formulations could be detected with respect to the effect on serum lipids and lipoproteins measured. The change in total cholesterol was smaller than reported in many studies of monophasic preparations. Taken together, these data suggest that only small alterations in lipid metabolism are elicited by these oral contraceptives.", "nan", "The effects of two oral contraceptives, containing gestodene and either 20 micrograms or 30 micrograms ethinylestradiol, on hemostatic parameters was investigated in a six-month randomized study involving a total of 40 healthy women between the ages of 18 and 30 years. A large number of hemostatic parameters were measured, which were categorized as either pro-coagulatory, anti-coagulatory, profibrinolytic, anti-fibrinolytic or indicative of fibrin turnover. Additionally, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) were measured before and after venous occlusion and delta and ratio values calculated. Pro-coagulatory factors as well as reaction products reflecting in vivo coagulatory activity (thrombin-antithrombin III complex, prothrombin fragment 1 + 2) were found to increase. Among the anti-coagulatory parameters, only protein S concentration and protein S activity decreased, most notably in the 30 micrograms EE group. There was a corresponding increase in fibrinolytic activity reflected by reaction products of in vivo fibrinolysis (plasmin-antiplasmin 2-complex, fibrin-degradation products). Measurement of t-PA and PAI-1, before and after venous occlusion, revealed that the fibrinolytic response was more pronounced in the 20 micrograms EE group. There was also an increase in the threshold of fibrinolytic inhibition (ratio PAI-1) in both groups, which was less pronounced in the 20 micrograms EE group. Apart from isolated measurements, all parameters remained within their normal ranges and values returned to baseline in the follow-up cycle. It is concluded that both preparations had a balanced effect on the hemostatic system stimulating both pro-coagulant and fibrinolytic activity. No statistically significant differences were observed between the two groups; however, there was a trend towards greater fibrinolytic capacity in the 20 micrograms EE group.", "The effect of two triphasic oral contraceptives (Triquilar [TRQ] and Trisiston [TRS]) containing ethinyl estradiol (EE) and levonorgestrel (LNG) on various hormonal parameters was investigated in 26 women during a cross-over study. TRS consisted of 0.03 mg EE + 0.05 mg LNG (six tablets), 0.04 mg EE + 0.075 mg LNG (six tablets), and 0.03 mg EE + 0.15 mg LNG (nine tablets), whereas TRQ was different in the second phase (five tablets) and third phase (10 tablets). Blood samples were taken on days 6, 11, 21, and 28 of the control and washout cycles and the third treatment cycle. Both formulations inhibited ovulation reliably and decreased the serum levels of gonadotropins, free testosterone, and dehydroepiandosterone sulfate in a time-dependent manner, whereas estradiol and testosterone were already suppressed on day 6, indicating a direct suppressive effect on ovarian steroid synthesis. Prolactin, which rose sporadically in some women, was not significantly changed. In contrast, the levels of sex hormone binding globulin, corticosteroid binding globulin, and cortisol were significantly elevated by 100%. During the hormone-free interval of 7 days, all parameters returned at least partly to baseline. There was no significant difference between the effects of both formulations. The results suggest the possibility of a direct inhibitory effect of contraceptive steroids on ovarian steroid synthesis.", "This study compares the contraceptive reliability, cycle control, and tolerability of two oral contraceptive preparations containing 20 micrograms of ethinyl estradiol combined with either 75 micrograms of gestodene (EE/GSD) or 150 micrograms of desogestrel (EE/DSG). Women received the trial preparations daily for 21 days, followed by a 7-day pill-free interval. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of 12 cycles. Efficacy data of 14,700 treatment cycles (EE/GSD: 7299; EE/DSG: 7401) were obtained from 1476 women (EE/GSD, n = 740; EE/DSG, n = 736). Both preparations provided effective contraception and good cycle control with a similarly low incidence of both spotting and breakthrough bleeding. The spotting rates in both treatment groups decreased from 35.1% (EE/GSD) and 37.5% (EE/DSG) in the first treatment cycle to approximately 10% in the fourth treatment cycle. The spotting incidence as percent of the total number of cycles was 12.7% for EE/GSD and 14.3% for EE/DSG. The breakthrough bleeding incidence was 5.2% of all cycles for EE/GSD and 6.0% of all cycles for EE/DSG. For 84.7% of the cycles in the gestodene group and for 82.5% of the cycles in the desogestrel group, neither spotting nor breakthrough bleeding were recorded. Overall, the spotting and breakthrough bleeding incidence tended to be lower with EE/GSD than with EE/DSG. However, the difference was not statistically significant. Amenorrhea was recorded in 2.7% of the cycles with EE/GSD and in 2.9% with EE/DSG. Both preparations were well tolerated and showed a similar pattern of adverse events. More than 83% of the women in both groups either did not gain weight or lost more than 2 kg. Both preparations had a beneficial effect on dysmenorrhea. Both regimens provided reliable contraception and good cycle control. The incidence of adverse events was relatively low and both preparations were well tolerated.", "The aim of this study was to compare contraceptive reliability, cycle control, and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol (EE2) and 75 micrograms gestodene (GSD), with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol. A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive. For the 20 micrograms EE2 preparation, 47.4% of all women reported spotting at least once over a period of 12 treatment cycles, whereas this figure was 35.5% for the 30 micrograms EE2 pill (p < 0.05). However, the incidence was within a range that corresponds to that of other OCs. The cumulative breakthrough bleeding rates (at least once during the one year of treatment) of 14.5% (20 micrograms EE2) and 11.8% (30 micrograms EE2) of women were not significantly different. In relation to all cycles, the intermenstrual bleeding rates were remarkably lower, indicating that the majority of the volunteers experienced such events only in few cycles under treatment: the spotting rate was 11.5% (20 micrograms EE2) and 7.2% (30 micrograms EE2) of all cycles, and the breakthrough bleeding rate was 2.6% and 1.6% of all cycles, respectively. Three pregnancies were recorded during the study (one in the 20 micrograms EE2 + 75 micrograms GSD group, two in the 30 micrograms EE2 + 75 micrograms GSD group). All three could be explained either by intake irregularities or by circumstances impairing the contraceptive effect. The influence of both treatments on the blood pressure and body weight proved to be extremely slight. Adverse events in both groups were rare and differences in the frequency of adverse events were not apparent. The discontinuation rate due to adverse events, including intermenstrual bleeding, was low (9.8% for 20 micrograms EE2 + 75 micrograms GSD, and 7.2% for 30 micrograms EE2 + 75 micrograms GSD) and was in the lower range known for other oral contraceptives. Both preparations were well accepted by the volunteers. The data obtained demonstrate clinically acceptable cycle control, good tolerance, and a high standard of contraceptive reliability for both drugs. Prescription of the 20 micrograms EE2 preparation could be the first-line therapy in order to provide the lowest amount of EE2 possible. In case of persistent cycle control problems, a switch to the 30 micrograms EE2 drug should be considered.", "This prospective, open, randomized study was conducted to compare the contraceptive reliability, cycle control, and tolerability of a 23-day regimen with 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) and a 21-day regimen with 20 microg EE and 150 microg desogestrel (DSG). Participants took either 23 tablets with active substances plus 5 placebo tablets (23-day EE/GSD) or 21 tablets with active substances followed by 7 days without pill-taking (21-day EE/DSG). Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of seven cycles. Efficacy data gathered from 5967 treatment cycles (23-day EE/GSD: 2975 cycles; 21-day EE/DSG: 2992 cycles) were obtained from 890 participants (445 in each group). Both preparations proved to be effective contraceptives and provided good cycle control. No pregnancy during treatment was recorded. This resulted in a study Pearl Index of 0.0 for both treatments. For 23-day EE/GSD, 32.4% of participants reported at least one intracyclic bleeding episode during Cycles 2-4 (primary target) compared to 31.5% for 21-day EE/DSG. In the 23-day EE/GSD group, intracyclic bleeding episodes were reported by 48.8% of the participants in Cycle 1 but in only 15.1% in Cycle 7, and in the 21-day regimen group by 43.4% in Cycle 1 and only 14.2% in Cycle 7. Overall, intracyclic bleeding was reported in 20.9% of cycles for both treatments.A greater number of 23-day EE/GSD participants had shorter withdrawal bleeding periods than with 21-day EE/DSG. In significantly (p <0.0001) more cycles in the 23-day EE/GSD group participants reported withdrawal bleeding periods that lasted only 1-4 days compared to the 21-day EE/DSG group. For the majority of the treatment cycles, the median number of bleeding days in the 23-day EE/GSD group was 4 days and in the 21-day EE/DSG group 5 days. Both preparations were well tolerated and showed a similar adverse events pattern. The discontinuation rate because of adverse events was low (23-day EE/GSD: 6.1%; 21-day EE/DSG: 5.6%). No serious vascular adverse events were reported. More than 82% in the 23-day EE/GSD group and 79% in the 21-day EE/DSG group either lost more than 2 kg of weight or did not gain weight during the study. The treatment effect on blood pressure was negligible. There were no appreciable changes in mean laboratory values over the course of the study compared to baseline.", "A comparison of cycle control, efficacy and tolerability of two oral contraceptive preparations containing 20 microg ethinylestradiol combined with either 100 microg levonorgestrel (EE/LNG 20/100) or 500 microg norethisterone (EE/NET 20/500) was conducted. These results were compared to a standard reference preparation, containing 30 microg ethinylestradiol combined with 150 microg levonorgestrel (EE/LNG 30/150). Efficacy data from 8,544 treatment cycles were obtained from 767 women. Good cycle control and effective contraception was achieved with the two LNG preparations, however, the cycle control results were less favorable with EE/NET 20/500. The cumulative incidence of women with at least one episode of intermenstrual bleeding from cycles 2 to 7 (primary target variable) was 43.9% for EE/LNG 20/100, 72.7% for EE/NET 20/500, and 15.7% for the standard EE/LNG 30/150. The difference between the 2 20 microg of EE preparations, which favored EE/LNG 20/100, was statistically significant (p = 0.001). The overall spotting rates (cycles 1-13) were 9.3% for EE/LNG 20/100, 21.7% for EE/NET 20/500, and 3.3% for the standard EE/LNG 30/150. Amenorrhea was reported in 7.1% (EE/LNG 20/100), 20.6% (EE/NET 20/500), and 0.9% (standard EE/LNG 30/150), respectively. Intermenstrual bleeding episodes were shorter with EE/LNG 20/100 and EE/LNG 30/150 of the 13 treatment cycles. The study Pearl indices were 0.9 for EE/LNG 20/100, 1.9 for EE/NET 20/500, and 0.0 for EE/LNG 30/150. All three treatments were well tolerated. However, tolerability was somewhat less favorable with EE/NET 20/500. A total of 160 women prematurely discontinued the study for various reasons (EE/LNG 20/100: 7%; EE/NET 20/500: 18%; EE/LNG 30/150: 4%). The overall adverse event incidence rate during the trial was low in all groups. Blood pressure remained largely unaffected. Thirteen serious adverse events were recorded for all treatment groups, all but one were assessed as not related to the treatments. There were no remarkable treatment related differences in mean body weight throughout the study and the laboratory values were largely unaffected in all three treatments groups.", "To compare the cycle control and tolerability of two oral contraceptives containing 20 micrograms ethinylestradiol and either 150 micrograms desogestrel or 75 micrograms gestodene.\n A randomized, multicenter study was conducted in which 1016 healthy adult women received the desogestrel (n = 509) or the gestodene (n = 507) preparation for six treatment cycles.\n No significant differences in bleeding patterns were detected between the two treatments. The incidence and duration of irregular bleeding decreased markedly, and to a similar extent, during each treatment. The occurrence of irregular bleeding per cycle decreased from 24.6 to 9.4% in the desogestrel group and from 19.7 to 8.6% in the gestodene group. Its duration fell from 1.1 to 0.2 days and from 0.9 to 0.3 days, respectively. There was a consistently low incidence of amenorrhea (1.0-2.8%). There were no significant differences between treatments for the incidence, intensity or emergence of dysmenorrhea. During both treatments, the incidence of premenstrual syndrome and complaints such as breast tenderness, nausea and headache dropped markedly.\n Ultra low-dose oral contraceptives containing desogestrel or gestodene offer equivalent, good cycle control and improvements in dysmenorrhea and premenstrual syndrome and have similar, excellent tolerability profiles.", "An open comparison at a single center was performed in volunteers (n = 58) randomly allocated to two treatment groups, one receiving tablets containing 20 micrograms ethinylestradiol (EE) + 75 micrograms gestodene, and the other 30 micrograms EE + 75 micrograms gestodene. The study consisted of three treatment-free pre-cycles, followed by thirteen 28-day treatment cycles. Analysis of results revealed that there were no statistically significant differences between the two groups with regard to the plasma levels of HDL-cholesterol and its subfractions, LDL-cholesterol and apolipoproteins. There was, however, a trend toward a more favorable effect on HDL-cholesterol in the 20 micrograms EE group, where levels increased by 3% compared with the 30 micrograms EE group, where levels decreased by 9%. There was a statistically significant difference between the adjusted mean values of total triglycerides in the two groups in favor of the 20 micrograms EE group (+21%), compared with the 30 micrograms EE group (+64%) (p = 0.029). Two serious adverse events were reported (lymphadenopathy and vertigo), but neither were considered to be causally related to either study medication. The formulation containing 75 micrograms gestodene and 20 micrograms EE was shown to be a reliable and well tolerated oral contraceptive, with a favorable lipid profile.", "To compare the effect of 2 oral contraceptives (OCs) on body weight.\n A randomized, parallel-group, multicenter study of 1,723 women taking an OC with norgestimate (NGM) 180/215/250 microg/ethinyl estradiol (EE) 25 microg vs. 1,171 women taking on OC with norethindrone acetate 1 mg/EE 20 microg for 6-13 cycles was performed. Body weight changes between baseline and cycle 6 and baseline and cycle 13 were analyzed. Analysis included not only changes in mean body weight but also the distribution of changes that were within 5% of baseline weight, 5-10% of baseline weight and > 10% of baseline weight. Only the 10% change was felt to be clinically significant.\n The distribution of body weight changes did not statistically differ between the 2 OC groups for any parameter measured. The mean weight change after 6 months for the NGM/EE and norethindrone acetate/EE groups was +0.71 kg and +0.57 kg, respectively. At 13 cycles for the NGM/EE and norethindrone acetate/ EE groups, the mean body weight change was +0.93 kg and +0.62 kg, respectively. Only 0.3% of subjects in both OC groups experienced a 10% change in weight.\n Use of OCs does not substantially affect body weight for most women.", "A randomized multicenter study was performed in order to investigate the acceptance of a low-dose OC (30 micrograms of ethinyloestradiol and 150 micrograms of desogestrel), using a 9 weeks on and 1 week off schedule (prolonged regimen, n = 198), compared to a traditional 3 weeks on, 1 week off schedule (standard regimen, n = 96). Haemoglobin and blood pressure remained the same in both groups during the study. No significant differences were found in body weight changes between the two groups. There was significantly more breakthrough bleeding and spotting in the group with prolonged regimen than in the group with standard regimen, but both breakthrough bleeding and spotting decreased during the trial. Irregular bleeding was significantly less in women who were already using OC, compared to \"new starters.\" No serious side effects occurred. Significantly more women stopped the trial because of bleeding problems in the group with prolonged regimen, while there were significantly more women who stopped the trial because of headache in the group with standard regimen. After completing 12 months, or after premature withdrawal from the study, each women completed a questionnaire. Sixty-three per cent of the women preferred the studied alternative and twenty-six per cent preferred the traditional OC.", "To examine the effect of oral contraceptives (OC) on body weight, fat mass, percent body fat, and lean mass in young female distance runners.\n The study population consisted of 150 female competitive distance runners aged 18-26 yr who had participated in a 2-yr randomized trial of the effect of the OC Lo/Ovral (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) on bone health. Weight and body composition were measured approximately yearly by balance beam scales and dual-energy x-ray absorptiometry, respectively.\n Women randomized to the OC group tended to gain slightly less weight (adjusted mean difference (AMD) = -0.54 +/- 0.31 kg.yr, P = 0.09) and less fat (AMD = -0.35 +/- 0.25 kg.yr, P = 0.16) than those randomized to the control group. OC assignment was associated with a significant gain in lean mass relative to controls among eumenorrheic women (those who had 10 or more menstrual cycles in the year before baseline; AMD = 0.77 +/- 0.17 kg.yr, P < 0.0001) but not among women with fewer than 10 menstrual cycles in that year (AMD = 0.02 +/- 0.35 kg.yr, P = 0.96). Treatment-received analyses yielded similar results.\n This randomized trial confirms previous findings that OC use does not cause weight or fat mass gain, at least among young female runners. Our finding that this OC is associated with lean mass gain in eumenorrheic runners, but not in those with irregular menses, warrants examination in other studies.", "nan", "Metabolic parameters were studied in 30 patients over 12 treatment cycles in a double-blind randomized comparative trial of the new progestogen gestoden in a triphasic formulation against a fixed dose combination pill containing desogrestrel, in Bandung, Indonesia. The results of this laboratory experience affirm findings in similar previous metabolic studies that: (1) the changes induced by modern low-dose pills are clinically and statistically insignificant; (2) throughout the treatment cycles, the values of the various laboratory tests remain well within the normal range; and (3) the favorable balance between coagulation and fibrinolysis is maintained. Results of lipoprotein, coagulation, fibrinolytic and liver function tests in 27 patients are presented. Gestoden's pharmacologic profile and the worldwide clinical experience with the triphasic gestoden formulation in 4285 women are discussed.", "The aim of the present study was to compare changes in the endogenous androgen environment in healthy women while on low-dose oral contraceptives (OCs). One-hundred healthy women were randomized to receive one of four OCs during six months: 21 tablets of Cilest, Femodeen, Marvelon, or Mercilon. During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded and the following parameters were measured: sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), testosterone (T), free testosterone (FT), 5 alpha-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S) and 17 alpha-hydroxyprogesterone (170HP) while also the free androgen index (FAI) was calculated. Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month. There were no differences on body mass and blood pressure with the use of the four OCs. The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon (approximately 20% vs 45%). Mean serum SHBG and CBG increased significantly in all four groups approximately 250% and 100%, respectively. In each group CBG also increased significantly but less in women taking Mercilon (-75%) as compared to the others (-100%). Current low-dose OCs were found to have similar impact on the endogenous androgen metabolism with significant decreases of serum testosterone, DHT, A, and DHEA-S. They may be equally beneficial in women with androgen related syndromes such as acne and hirsutism.", "The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone.\n A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles.\n Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences.\n NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweight.", "To compare bleeding profiles and satisfaction among women using a norelgestromin/ethinyl estradiol (E2) transdermal contraceptive patch in an extended regimen to those among women using a traditional 28-day patch regimen.\n Healthy, regularly menstruating women (N = 239) were randomly assigned (2:1 ratio) to receive the norelgestromin/ethinyl E2 transdermal patch in an extended regimen (weekly application for 12 consecutive weeks, 1 patch-free week, and 3 more consecutive weekly applications, n = 158) or a cyclic regimen (4 consecutive cycles of 3 weekly applications and 1 patch-free week, n = 81). Subjects recorded bleeding data daily and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens.\n Extended use of the norelgestromin/ethinyl E2 transdermal patch resulted in fewer median bleeding days (6 compared with 14, P < .001), bleeding episodes (1 compared with 3, P < .001), and bleeding or spotting episodes (2 compared with 3, P < .001) compared with cyclic use during days 1-84; median numbers of bleeding or spotting days were similar between regimens (14 compared with 16, P = .407) during this time. Extended use delayed median time to first bleeding to 54 days compared with 25 days with cyclic (P < .001). Subjects were highly satisfied with both regimens. Although not statistically significant, slightly more adverse events were reported with the extended than with the 28-day regimen.\n Compared with cyclic use, extended use of the norelgestromin/ethinyl E2 transdermal patch delayed menses and resulted in fewer bleeding days. This regimen may represent a useful alternative for women who prefer fewer episodes of withdrawal bleeding.", "This prospective, randomized comparative clinical study involving 416 women investigated follicle development over a period of 12 oral contraceptive treatment cycles. Women were allocated to two groups, one group (n = 207) received a preparation containing 30 micrograms ethinylestradiol and 75 micrograms gestodene daily, and the other group (n = 209) received 20 micrograms ethinylestradiol and 150 micrograms desogestrel, daily. Follicular development was monitored by transvaginal ultrasonography of the ovaries, during days 18-21 in the pretreatment cycle and in treatment cycles 1, 3, 6, 9 and 12. Follicular development was found to be twice as frequent in the group receiving 20 micrograms ethinylestradiol/desogestrel as in the group receiving 30 micrograms ethinylestradiol/gestodene. For all cycles, follicles of 10-30 mm were found in 18% of women in the desogestrel group, compared with 9.7% in the gestodene group, whilst follicles with a diameter of >30 mm were present in 5% of the desogestrel group compared with 1.9% of the gestodene group. The difference between the treatment groups with respect to follicle diameters of 10-30 mm and >30 mm was statistically significant (p < 0.05 and p < 0.001, respectively). No ruptured follicles were observed in either group throughout the study, suggesting that there was no escape ovulation, however, there was one pregnancy in the desogestrel group that could not be explained either by drug interactions or missed pills. It can be concluded that the ethinylestradiol dose in an oral contraceptive has a significant effect on follicular ovarian activity, and that reducing the dose to 20 micrograms is associated with a significant increase in follicle size.", "The objective of the study was to determine the suppressive effect on ovarian activity of 20 micrograms ethinylestradiol plus 75 micrograms gestodene administered for 21 or 23 days. The study was designed as a double-blind, randomized, multicenter trial in 60 women. A pre-treatment cycle, three treatment cycles and a post-treatment period were monitored by ovarian ultrasound and by LH, FSH, 17 beta-estradiol and progesterone measurements every other day. No ovulation and no luteinized, unruptured follicle were observed. Suppression of ovarian activity was more pronounced by the 23-day regimen. 17 beta-Estradiol serum levels during the last six days of a cycle and during the first six days of the next cycle were significantly less (p < 0.05) in the 23-day regimen. The superiority of the 23-day regimen in comparison to the 21-day regimen with regard to the suppression of ovarian activity was shown in this study. The observed differences in the 17 beta-estradiol levels and follicular development between a 21-day and 23-day preparation combine to suggest that shortening the pill-free interval in combined oral contraceptives may increase the contraceptive safety margin in women on low-dose formulations.", "Desogestrel (DSG) is a less-androgenic progestogen than levonorgestrel (LNG). This difference in androgenicity may be responsible for observed differences in metabolic effects between oral contraceptive (OC) formulations containing almost equivalent estrogen doses but with either DSG or LNG as a progestogen. To test the hypothesis, a prospective 9-month randomized comparison of plasma lipids, glucose, insulin, hemostasis, and sex hormone binding globulin (SHBG) was conducted in 66 healthy women using phasic formulations of OCs containing either DSG (DSG-OC) or LNG (LNG-OC). The study results showed that SHBG increased 3-fold with DSG-OC and 2-fold with LNG-OC. DSG-OC increased HDL-C, HDL(2)-C and HDL(3)-C; LDL-C decreased transiently. LNG-OC decreased HDL(2)-C and increased HDL(3)-C; HDL-C was unchanged and LDL-C decreased transiently. Both formulations increased VLDL-C and triglycerides, more with DSG-OC, but apolipoprotein B levels increased equally. Apo A-I and A-II increased more with DSG-OC than with LNG-OC. Neither formulation altered Lp(a) or fasting glucose and insulin levels. Postprandially, both formulations decreased glucose and increased insulin responses, but to an equivalent degree. Both OCs slightly enhanced procoagulant and profibrinolytic parameters to the same extent except for internally compensating decreases in Factor V and protein S with DSG-OC. In summary, at almost equivalent estrogen doses, a phasic OC containing DSG compared with LNG has a less androgenic effect on lipoproteins and SHBG, similar effects on hemostatic parameters with lower protein S and factor V activity and equivalent effects on carbohydrate metabolism. The lipoprotein, SHBG, and protein S and factor V differences are likely due to the lesser androgenicity of DSG allowing for a greater expression of the dose of estrogen.", "To determine in a prospective study if the use of two low-dose estrogen oral contraceptives is associated with changes in weight or body composition.\n 80 outpatients referring to the family planning service, aged 18-43 years were randomly assigned to a treatment with the EE/desogestrel or EE/gestodene association, 20 patients with IUD, aged 26-40 years, were selected as a control group. Anthropometric data and body composition were taken at enrollment and after 6 and 12 months.\n Anthropometric measurements included body mass index (BMI), body composition estimated by mean of Bioelectrical Impendance Analysis (BIA).\n In the three groups weight, BMI, and total body water (TBW), and body cellular mass (BCM) remained unchanged during the study period.\n The use of EE/desogestrel and EE/gestodene is not associated with significant variations of body weight and body composition during one year treatment.", "Combined hormonal oral contraceptives (OCs) may lead to a mild rise in blood pressure and body weight. In rare instances, large increments in blood pressure are measured. We investigated the effect of a combination of ethinyl estradiol (EE) plus a progestogen with antimineralocorticoid, i.e. natriuretic, properties [Drospirenone (DRSP)] on body weight, blood pressure, the renin-aldosterone system, atrial natriuretic factor, plasma lipids, and glucose tolerance. It is anticipated that this will lead to the development of an OC that does not raise body weight or blood pressure. Four groups of 20 women each received 30 micrograms EE plus 3 mg DRSP (group A), 20 micrograms EE plus 3 mg DRSP (group B), 15 micrograms EE plus 3 mg DRSP (group C), and, as a control OC, 30 micrograms EE plus 150 micrograms levonorgestrel (Microgynon, Schering; group D) for 6 months. During the OC-free control cycles before and after treatment and throughout treatment, the target parameters were measured. Between the pretreatment cycle and the sixth treatment cycle, mean body weight fell by 0.8 to 1.7 kg in groups A, B, and C (P < 0.05 vs. D), whereas it rose by 0.7 kg in group D. Systolic and diastolic blood pressures fell by 1-4 mm Hg in groups A, B, and C (significant for A and C vs. D) and increased by 1-2 mm Hg in group D. Renin substrate rose equally in all groups (P < 0.05), whereas PRA and plasma aldosterone rose significantly only in the DRSP groups, presumably due to sodium loss. In the DRSP groups, high density lipoprotein cholesterol rose (P < 0.05), in contrast to group D. Low density lipoprotein cholesterol fell slightly (P > 0.05), whereas triglyceride levels showed a stronger increase in the DRSP groups (P < 0.05) than in group D. All groups attained good cycle control; group A had the best. Side-effects were minimal. To our knowledge, this is the first report on a combined OC that leads to a small decrease in body weight and blood pressure. It may be especially beneficial for women susceptible for a gain in weight and a rise in blood pressure.", "Drospirenone is a new synthetic progestogen with both progestational, antimineralocorticoid and antiandrogenic properties. In combination with ethinylestradiol, it is being developed as an oral contraceptive which will contain 30 micrograms ethinylestradiol and 3 mg drospirenone (Yasmin, Schering AG, Germany). The effects of drospirenone alone, and in combination with ethinylestradiol, upon the renin-angiotensin-aldosterone system (RAAS) have been evaluated in healthy female volunteers. RAAS activity was assessed by measurement of plasma renin substrate (PRS) concentration (otherwise known as angiotensinogen), plasma renin activity (PRA), and plasma aldosterone (P-Aldo) concentration. An antimineralocorticoid effect was observed when volunteers received drospirenone alone at doses in the range 0.5-3.0 mg/day for one cycle. The effect was dose-dependent for P-Aldo but was not dose-dependent for PRA. When ethinylestradiol (30 micrograms) was combined with either 2 mg or 3 mg drospirenone and given to volunteers for three cycles, an increase in PRS was observed with both preparations, which was indicative of estrogenic stimulation, and increases in PRA and P-Aldo were shown which were indicative of an antimineralocorticoid effect of drospirenone. Increases in PRA and P-Aldo were significantly higher with the preparation containing 3 mg drospirenone in cycle 1 but not in cycle 3. The effect of the preparation containing 30 micrograms ethinylestradiol/3 mg drospirenone upon RAS activity was also compared with that of a commercially available preparation also containing 30 micrograms ethinylestradiol but combined with 150 micrograms desogestrel (Marvelon). Over a period of 13 cycles, increases in PRS were seen with both treatments, the effect being slightly more pronounced with 30 micrograms ethinylestradiol/150 micrograms desogestrel. A markedly greater increase in PRA was seen following treatment with 30 micrograms ethinylestradiol/3 mg drospirenone, and, in cycle 3, this difference was statistically significant. In contrast, P-Aldo was increased markedly with 30 micrograms ethinylestradiol/3 mg drospirenone in all measured cycles, whereas, in the 30 micrograms ethinylestradiol/150 micrograms desogestrel group, changes were minimal. The increases in PRA and P-Aldo are interpreted as endogenous counter-regulation against the antimineralocorticoid activity of drospirenone. PRS increases under all combinations are an expression of estrogenic stimulation. Measurement of body weight and blood pressure in the studies with combined ethinylestradiol and drospirenone revealed that drospirenone was associated with either stable body weight or with a slight loss in body weight, while blood pressure remained largely unchanged. Overall, the results indicate that 30 micrograms ethinylestradiol/3 mg drospirenone has a distinct antimineralocorticoid effect.", "nan", "In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on lipid metabolism was investigated. Four groups composed of 25 volunteers each (mean age 26.1 +/- 4.5 years; body mass index 21.9 +/- 2.8 kg/m(2)) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinyl estradiol (EE) + 2 mg dienogest (DNG) (30 EE/DNG), 20 microg EE + 2 mg DNG (20 EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG), or 20 microg EE + 100 microg levonorgestrel (LNG; EE/LNG). The study was completed by 91 women. Blood samples were taken by venipuncture after at least 12 h fasting on Days 21-26 of the control cycle and Days 18-21 of the first, third, and sixth treatment cycle. There were clear differences between the effects of EE/LNG and the formulations containing estrogens and DNG. Although EE/LNG did not change the triglycerides levels, a significant increase was observed during treatment with the DNG-containing preparations. Although EE/LNG significantly reduced HDL-CH and HDL(2)-CH, there was a nonsignificant increase with the DNG-containing OCs. No change was observed in the levels of HDL(3)-CH. A significant rise in apolipoprotein A1 occurred during intake with the three DNG-containing formulations, but not with EE/LNG. In contrast to the women treated with combinations of estrogens and DNG, apolipoprotein B rose significantly in the women in the EE/LNG group. Lipoprotein (a) was significantly reduced by 30 EE/DNG and EE/LNG and remained unaltered with 20 EE/DNG and EE/EV/DNG. Altogether, the changes in lipid metabolism caused by the DNG-containing formulations appeared to be more favorable than those observed with EE/LNG. In OCs with DNG, the EE dose does not seem to play a major role with respect to the effect on lipids.", "To compare the cycle control, efficacy, and safety of a new low-dose combined oral contraceptive containing ethinylestradiol 20mug and drospirenone 3mg with an established formulation containing ethinylestradiol 20mug and desogestrel 150mug.\n This was a randomized, open-label, parallel-group, multicenter study of healthy women (aged 18-35 years) over seven treatment cycles. Both combined oral contraceptives were administered once daily for 21 consecutive days followed by a 7-day hormone-free interval.\n A total of 445 women were randomized to treatment; of these, 441 (ethinylestradiol 20mug/drospirenone 3mg, n = 220; ethinylestradiol 20mug/desogestrel 150mug, n = 221) went on to receive study medication. There was a trend towards reduced intracyclic bleeding with continued treatment in both treatment groups, consistent with clinical experience. Intracyclic bleeding was highest during the first treatment cycle in both treatment groups, but was generally much lower in subsequent cycles. More than 90% of women in each of the groups experienced withdrawal bleeding during the study. The duration of withdrawal bleeding remained fairly constant throughout the study. The maximum intensity was mainly bleeding, rather than spotting. Overall, cycle control, efficacy, and safety profiles were comparable between both groups. Adverse events were generally of mild-to-moderate intensity and were those typical of hormonal contraceptive use.\n In conclusion, both ethinylestradiol 20mug/drospirenone 3mg and ethinylestradiol 20mug/desogestrel 150mug are effective and well tolerated contraceptives that provide good cycle control.", "A comparative study of two low-dose oral contraceptives, gestodene (GES) 75 mcg/ethinyl oestradiol (EE) 30 mcg and desogestrel (DES) 150 mcg/EE 20 mcg, was conducted in women over 30 years of age. This randomised, open-label study was organised in Denmark, Italy, New Zealand and United Kingdom. A total of 505 women received GES/EE and 501 received DES/EE for 6 consecutive menstrual cycles. The two groups were comparable in terms of demographic and gynaecologic characteristics at baseline. However, the menstrual flow length was slightly longer in the GES/EE group before the start of the treatment. The mean age (+/- SD) was 35 +/- 4 years in the GES/EE group and 35 +/- 5 years in the DES/EE group. The subjects in the GES/EE group contributed data for a total of 2800 cycles and those in the DES/EE group, data for 2796 cycles. There were no pregnancies on medication with either preparation. The results showed that there were significantly more normal cycles in the GES/EE group for cycles 1 to 6. Irregular bleeding between withdrawal bleeds occurred in 10% of GES/EE and 18.5% of DES/EE cycles. Absence of all bleeding was reported in 29 (1%) and 63 (2%) cycles, respectively. The incidence of missed pills was low in both groups (11% of cycles). No significant differences were observed in cycle length or withdrawal bleeding episode length. Withdrawal bleeding mean intensity was statistically significantly greater with GES/EE. However, for both preparations, the mean intensity was close to light bleeding. No clinically significant differences were noted in weight, blood pressure, Papanicolaou smears or laboratory data. Sixty-eight (13.5%) subjects in the GES/EE group and 64 (12.8%) in the DES/EE group discontinued before the end of the study. Among them, 37 (7%) and 40 (8%) in the respective groups withdrew because of adverse reactions. There was no difference between groups in terms of primary reasons for withdrawal. The most frequently reported complaints that led to discontinuation in both groups were headache, nausea and metrorrhagia. Breast tenderness led to the discontinuation of 1 subject in the GES/EE group and 3 in the DES/EE group. These results show excellent cycle control, efficacy and very low rate of side effects with both GES/EE and DES/EE. These low-dose oral contraceptives could be well suited to healthy nonsmoking women requiring contraception up to the age of menopause.", "Oral contraceptive pills (OCPs) are one of the most effective reversible and accessible contraceptives, and patient acceptance for their use depends partly on the unfavorable adverse effects. The present study compared the two kinds of OCPs (monophasic; levonorgestrel (LNG)-ethinyl estradiol (EE) 150/30 versus triphasic; LNG-EE 50-75-125/30-40-30) for adverse effects and patient satisfaction.\n A randomized clinical trial was performed on 314 women who used OCPs for the first time, as their contraception, for 6 months. Overall, 1884 cycles were studied. In the monophasic group (n=159 who finally finished the study), monophasic pills LNG-EE 150/30mcg, and in the triphasic group (n=155 who finally finished the study), triphasic pills LNG-EE 50-75-125/30-40-30 mcg were used. Statistical analysis was performed using SPSS 10: Chi square test, Fisher exact test and Student's t-test were used.\n There were no significant differences between the two groups for common side effects, including nausea, headache, nervousness, facial hyperpigmentation (chloasma), and body weight (increase or decrease) but breakthrough bleeding and spotting (BTB/S) were less in the triphasic group, occurring in 30 cycles (18.86%) versus 10 cycles (6.45%), P=0.009*. Patient satisfaction for the two OCPs was similar and high. The rates of side effects were low.\n It seems that the monophasic and triphasic pills are similar according to patient satisfaction and side effects; therefore there is no benefit of one over the other except for BTB/S, for which triphasic is superior.\n Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.", "nan" ]

[ "20308616" ]

[ "Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept pilot study." ]

[ "Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease that occurs in previously healthy women. We identified prolactin, mainly its 16-kDa angiostatic and proapoptotic form, as a key factor in PPCM pathophysiology. Previous reports suggest that bromocriptine may have beneficial effects in women with acute onset of PPCM.\n A prospective, single-center, randomized, open-label, proof-of-concept pilot study of women with newly diagnosed PPCM receiving standard care (PPCM-Std; n=10) versus standard care plus bromocriptine for 8 weeks (PPCM-Br, n=10) was conducted. Because mothers receiving bromocriptine could not breast-feed, the 6-month outcome of their children (n=21) was studied as a secondary end point. Blinded clinical, hemodynamic, and echocardiographic assessments were performed at baseline and 6 months after diagnosis. Cardiac magnetic resonance imaging was performed 4 to 6 weeks after diagnosis in PPCM-Br patients. There were no significant differences in baseline characteristics, including serum 16-kDa prolactin levels and cathepsin D activity, between the 2 study groups. PPCM-Br patients displayed greater recovery of left ventricular ejection fraction (27% to 58%; P=0.012) compared with PPCM-Std patients (27% to 36%) at 6 months. One patient in the PPCM-Br group died compared with 4 patients in the PPCM-Std group. Significantly fewer PPCM-Br patients (n=1, 10%) experienced the composite end point of poor outcome defined as death, New York Heart Association functional class III/IV, or left ventricular ejection fraction <35% at 6 months compared with the PPCM-Std patients (n=8, 80%; P=0.006). Cardiac magnetic resonance imaging revealed no intracavitary thrombi. Infants of mothers in both groups showed normal growth and survival.\n In this trial, the addition of bromocriptine to standard heart failure therapy appeared to improve left ventricular ejection fraction and a composite clinical outcome in women with acute severe PPCM, although the number of patients studied was small and the results cannot be considered definitive. Larger-scale multicenter and blinded studies are in progress to test this strategy more robustly." ]

[ "10199349", "10459958", "10459959", "10459957", "10485720" ]

[ "Elective caesarean-section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial.", "Short-course oral zidovudine for prevention of mother-to-child transmission of HIV-1 in Abidjan, Côte d'Ivoire: a randomised trial.", "6-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Côte d'Ivoire and Burkina Faso: a double-blind placebo-controlled multicentre trial. DITRAME Study Group. DIminution de la Transmission Mère-Enfant.", "Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial. Bangkok Collaborative Perinatal HIV Transmission Study Group.", "Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial." ]

[ "Results from observational studies suggest that caesarean-section delivery may reduce the risk of mother-to-child transmission of HIV-1 infection in comparison with vaginal delivery. We carried out a randomised clinical trial to address this issue and to assess the extent of postdelivery complications.\n Eligible women were between 34 and 36 weeks of pregnancy, with a confirmed diagnosis of HIV-1 infection, and without an indication for caesarean-section delivery or a contraindication to this mode of delivery. Women were randomly assigned elective caesarean-section delivery at 38 weeks of pregnancy or vaginal delivery. An infant was classified as uninfected if he or she became negative for antibody to HIV-1 by age 18 months or was negative for virus by PCR or culture on at least two occasions, with no clinical, immunological, or viral evidence of infection. From 1993, to March, 1998, 436 women were randomised.\n We present the results of an analysis updated to November, 1998, with data on the infection status of 370 infants. Three (1.8%) of 170 infants born to women assigned caesarean-section delivery were infected, compared with 21 (10.5%) of 200 born to women assigned vaginal delivery (p<0.001). Seven (3.4%) of 203 infants of women who actually gave birth by caesarean section were infected compared with 15 (10.2%) of 167 born vaginally (p=0.009). There were few postpartum complications and no serious adverse events in either group.\n Our findings provide evidence that elective caesarean-section delivery significantly lowers the risk of mother-to-child transmission of HIV-1 infection without a significantly increased risk of complications for the mother.", "In Africa, the risk of mother-to-child transmission of HIV-1 infection is high. Short-course perinatal oral zidovudine might decrease the rate of transmission. We assessed the safety and efficacy of such a regimen among HIV-1-seropositive breastfeeding women in Abidjan, Côte d'Ivoire.\n From April, 1996, to February, 1998, all consenting, eligible HIV-1-seropositive pregnant women attending a public antenatal clinic in Abidjan were enrolled at 36 weeks' gestation and randomly assigned placebo or zidovudine (300 mg tablets), one tablet twice daily until the onset of labour, one tablet at onset of labour, and one tablet every 3 h until delivery. We used HIV-1-DNA PCR to test the infection status of babies at birth, 4 weeks, and 3 months. We stopped the study on Feb 18, 1998, when efficacy results were available from a study in Bangkok, Thailand, in which the same regimen was used in a non-breastfeeding population.\n 280 women were enrolled (140 in each group). The median duration of the prenatal drug regimen was 27 days (range 1-80) and the median duration of labour was 7.5 h. Treatment was well tolerated with no withdrawals because of adverse events. All babies were breastfed. Among babies with known infection status at age 3 months, 30 (26.1%) of 115 babies in the placebo group and 19 (16.5%) of 115 in the zidovudine group were identified as HIV-1 infected. The estimated risk of HIV-1 transmission in the placebo and zidovudine groups were 21.7% and 12.2% (p=0.05) at 4 weeks, and 24.9% and 15.7% (p=0.07) at 3 months. Efficacy was 44% (95% CI -1 to 69) at age 4 weeks and 37% (-5 to 63) at 3 months.\n Short-course oral zidovudine was safe, well tolerated, and decreased mother-to-child transmission of HIV-1 at age 3 months. Substantial efforts will be needed to ensure successful widespread implementation of such a regimen.", "Zidovudine reduces the rate of vertical transmission of HIV in non-breastfed populations. We assessed the acceptability, tolerance, and 6-month efficacy of a short regimen of oral zidovudine in African populations practising breastfeeding.\n A randomised double-blind placebo-controlled trial was carried out in public clinics of Abidjan, Côte d'Ivoire, and Bobo-Dioulasso, Burkina Faso. Eligible participants were women aged 18 years or older, who had confirmed HIV-1 infection and pregnancy of 36-38 weeks duration, and who gave written informed consent. Exclusion criteria were severe anaemia, neutropenia, abnormal liver function, and sickle-cell disease. Women were randomly assigned zidovudine (n=214; 300 mg twice daily until labour, 600 mg at beginning of labour, and 300 mg twice daily for 7 days post partum) or matching placebo (n=217). The primary outcome was the diagnosis of HIV-1 infection in the infant on the basis of sequential DNA PCR tests at days 1-8, 45, 90, and 180. We compared the probability of infection at a given age in the two groups. Analyses were by intention to treat.\n Women were enrolled between September, 1995, and February, 1998, when enrolment to the placebo group was stopped. Analysis was based on 421 women and 400 lifeborn infants. Baseline demographic, clinical, and laboratory characteristics were similar in the two groups. The Kaplan-Meier probability of HIV infection in the infant at 6 months was 18.0% in the zidovudine group (n=192) and 27.5% in the placebo group (n=197; relative efficacy 0.38 [95% CI 0.05-0.60]; p=0.027). Adjustment for centre, period of recruitment, mode of delivery, maternal CD4-cell count, duration of labour, prolonged rupture of membranes, and duration of breastfeeding did not change the treatment effect. The proportions of women taking more than 80% of the planned maximum dose were 75% before delivery, 81% during labour, and 83% post partum, without statistical difference between the groups. No major adverse biological or clinical event was reported in excess among women and children of the zidovudine group.\n A short course of oral zidovudine given during the peripartum period is well accepted and well tolerated, and provides a 38% reduction in early vertical transmission of HIV-1 infection despite breastfeeding.", "Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost. We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour.\n In a randomised, double-blind, placebo-controlled trial, HIV-1-infected pregnant women at two Bangkok hospitals were randomly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks' gestation and every 3 h from onset of labour until delivery. Mothers were given infant formula and asked not to breastfeed. The main endpoint was babies' HIV-1-infection status, tested with HIV-1-DNA PCR at birth, 2 months, and 6 months. We measured maternal plasma viral concentrations by RNA PCR.\n Between May, 1996, and December, 1997, 397 women were randomised; 393 gave birth to 395 live-born babies. Median duration of antenatal treatment was 25 days, and median number of doses during labour was three. 99% of women took at least 90% of scheduled antenatal doses. Adverse events were similar in the study groups. Of 392 babies with at least one PCR test, 55 tested positive: 18 in the zidovudine group and 37 in the placebo group. The estimated transmission risks were 9.4% (95% CI 5.2-13.5) on zidovudine and 18.9% (13.2-24.2) on placebo (p=0.006; efficacy 50.1% [15.4-70.6]). Between enrolment and delivery, women in the zidovudine group had a mean decrease in viral load of 0.56 log. About 80% of the treatment effect was explained by lowered maternal viral concentrations at delivery.\n A short course of twice-daily oral zidovudine was safe and well tolerated and, in the absence of breastfeeding, can lessen the risk for mother-to-child HIV-1 transmission by half. This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen.", "The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries. We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life.\n From November, 1997, to April, 1999, we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala, Uganda. We randomly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth, or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily to babies for 7 days after birth. We tested babies for HIV-1 infection at birth, 6-8 weeks, and 14-16 weeks by HIV-1 RNA PCR. We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis.\n Nearly all babies (98.8%) were breastfed, and 95.6% were still breastfeeding at age 14-16 weeks. The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were: 10.4% and 8.2% at birth (p=0.354); 21.3% and 11.9% by age 6-8 weeks (p=0.0027); and 25.1% and 13.1% by age 14-16 weeks (p=0.0006). The efficacy of nevirapine compared with zidovudine was 47% (95% CI 20-64) up to age 14-16 weeks. The two regimens were well tolerated and adverse events were similar in the two groups.\n Nevirapine lowered the risk of HIV-1 transmission during the first 14-16 weeks of life by nearly 50% in a breastfeeding population. This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries." ]

[ "6175947", "7798839", "15123865", "4000778", "1552399" ]

[ "Neonatal hyperviscosity. II. Effect of partial plasma exchange transfusion.", "Developmental outcome of infants with neonatal polycythemia.", "Effect of partial exchange transfusion in asymptomatic polycythemic LBW babies.", "Neonatal hyperviscosity: randomized study of effect of partial plasma exchange transfusion on long-term outcome.", "Asymptomatic syndrome of polycythemic hyperviscosity: effect of partial plasma exchange transfusion." ]

[ "To determine the effect of partial plasma exchange transfusion, 20 newborn infants with neonatal hyperviscosity were randomly assigned to observation or treatment with partial plasma exchange transfusion within the first eight hours after birth. They were studied for organ involvement by roentgenogram, blood count, coagulation studies, and neurologic behavior and were followed up using the Brazelton Neonatal Behavior Assessment scale at 8, 24, and 72 hours and 2 weeks of age; in addition, ten control infants without hyperviscosity of similar birth weights and gestational ages were also studied. Exchange transfusion improved blood viscosity but both hyperviscous groups showed a higher proportion of abnormal results than did the control subjects. Infants receiving exchange transfusions subsequently improved during the period from 8 hours to 2 to 3 weeks of age, until they were indistinguishable from the control subjects. Neurologic improvement in hyperviscous infants who had not received exchange transfusions were significantly slower during this period. At 8 months of age, abnormal neurologic and developmental findings were impressive in both groups; no significant differences in neurologic abnormalities were noted at that time. Developmental delays, tremors, spastic diplegia, and monoparesis were found in four of six untreated infants and five of ten infants who had received exchange transfusions. A fine tremor was present in one control child.", "The study of the developmental outcome of neonatal polycythemia was performed on 47 polycythemic and 21 controlled infants who were born at the same period of time. It was found that at the age of 1 1/2 to 2 years the number of infants with abnormal DQ was higher in the group of total polycythemic infants (47%) and in the group of asymptomatic polycythemic infants (45%) than that of the control groups (19% and 5.6% of the groups including twin sibs and excluding twin sibs respectively). There was no difference in the developmental test between the symptomatic and asymptomatic patients. In asymptomatic infants the benefit of partial plasma exchange transfusion on developmental outcome was not found and only low birthweight and small for gestational age infants are the risk factors for poor developmental outcome.", "This randomized controlled trial was conducted to determine the effect of partial exchange transfusion in polycythemic babies. Forty five asymptomatic polycythemic babies with birth weight < or = 2000 g were included and randomly assigned to undergo either partial exchange transfusion using isotonic saline within 4 hours of screening or routine medical management. Outcome measures were neonatal morbidity (especially hypoglycemia and neurological alterations) and mortality; developmental delays using DDST-II, neurological deficits, tone and DTR abnormalities over 18 months follow up period. The overall neonatal morbidity in this study was low and comparable in the two groups. Some of the polycythemic babies in the non-exchanged group found initially at 3 months age with \"suspected development\" grew out of their developmental delay at 18 months of age or later while those who underwent exchange transfusion and with retarded development at 3 months of age remained so even at 18 months of age.", "The use of partial plasma exchange transfusion in newborns with polycythemia and hyperviscosity was evaluated. Ninety-three infants with polycythemia and hyperviscosity were randomly assigned to receive either partial plasma exchange transfusion or symptomatic treatment; the infants were matched with control infants without polycythemia. Neonatal course and outcome at 1 and 2 years were evaluated for each of the three groups. Polycythemic infants had more fine motor and speech problems at 1 year of age than did control infants. At 2 years of age, polycythemic infants had more gross motor delays, neurologic diagnoses, fine motor abnormalities, and speech delays than did the control infants. There was no significant difference at 1 year between the polycythemic infants who had received partial plasma exchange transfusion and those given only symptomatic care. At 2 years, the group receiving partial plasma exchange transfusion had fewer neurologic diagnoses and fine motor abnormalities.", "We determined the cerebral hemodynamic changes in infants with asymptomatic polycythemic hyperviscosity syndrome and whether treatment with partial plasma exchange transfusion (PPET) would affect hemodynamics as well as outcome. From a routine cord blood hematocrit screening, 71 babies were identified as needing to be tested for polycythemic hyperviscosity. In addition to clinical evaluation, each infant had radial artery hematocrit and viscosity determinations, blood gas determinations, cerebral blood flow velocity studies, cranial ultrasonography, and noninvasive intracranial pressure determination. Babies with symptomatic hyperviscosity (n = 17) were treated by PPET, whereas those with asymptomatic hyperviscosity (n = 28) were randomly selected to have PPET (n = 14) or to be observed (n = 14). The remaining babies (n = 26) with normal viscosity served as control subjects. Both hematocrit and viscosity decreased after PPET but remained unchanged in babies with hyperviscosity who were merely observed. Reversal of cerebral blood flow velocity abnormalities was observed after PPET in the infants with symptomatic hyperviscosity, whereas those who had no symptoms had normal results on Doppler studies at the outset, and no significant changes occurred with either PPET or observation. There were two deaths in the group with symptoms. A total of 46 babies returned for follow-up evaluation at a mean age of 30 +/- 7.7 months. Outcome of the control group was no better than that of those who had hyperviscosity, and outcomes did not differ between the babies with symptomatic and those with asymptomatic hyperviscosity, nor between those treated with PPET and those who were only observed. Multivariate analysis revealed that other perinatal risk factors and race rather than polycythemia or PPET, significantly influenced long-term outcome." ]

[ "15546536", "15785218", "19848576", "17116184" ]

[ "[Effectiveness of an intervention to provide information to patients with hypertension as short text messages and reminders sent to their mobile phone (HTA-Alert)].", "Improving asthma control through telemedicine: a study of short-message service.", "Computerized Automated Reminder Diabetes System (CARDS): e-mail and SMS cell phone text messaging reminders to support diabetes management.", "A randomized controlled trial of Sweet Talk, a text-messaging system to support young people with diabetes." ]

[ "To analyze the effect of an intervention to provide information with mobile phone text messages to patients with hypertension on compliance with therapy for hypertension.\n Comparative, controlled, multicenter, randomized cluster study.\n 26 primary care health centers in Spain.\n 26 researchers were randomized to a control group or an intervention group (52 patients each, for a total of 104 patients). All patients were receiving monotherapy for uncontrolled hypertension.\n Patients in the control group received their physician's usual interventions. Patients in the intervention group received messages and reminders sent to their mobile phones 2 days per week during 4 months.\n Tablets were counted and blood pressure was measured at the start of the study and 1, 3, and 6 months later. The percentage of compliers, mean percentage of compliance and degree of control of hypertension were compared. The reduction in absolute and relative risk was calculated, as was the number of individuals needed to treat to avoid noncompliance.\n The results were evaluated for a total of 67 individuals (34 in the intervention group and 33 in the control group). The rate of compliance was 85.1% (CI, 74.9%-95.3%) overall, 85.7% (CI, 70.5%-100.9%) in the control group and 84.4% in the intervention group (CI, 70.7%-95.3%) (P=NS). Mean percentage compliance was 90.2%+/-16.3% overall, 88.1%+/-20.8% in the control group and 91.9%+/-11.6% in the intervention group (P=NS). The percentage of patients whose hypertension was controlled at the end of the study was 51.5% (CI, 34.4%-68.6%) in the control group and 64.7% (CI, 48.6%-80.8%) in the intervention group (P=NS).\n The telephone messaging intervention with alerts and reminders sent to mobile phones did not improve compliance with therapy in patients with hypertension.", "Home peak expiratory flow (PEF) measurement is recommended by asthma guidelines. In a 16-week randomized controlled study on 16 subjects with asthma (24.6 6.5 years old, asthma duration small ze, Cyrillic 6 months), we examined Global System for Mobile Communications (GSM) mobile telephone short-message service (SMS) as a novel means of telemedicine in PEF monitoring. All subjects received asthma education, self-management plan, and standard treatment. All measured PEF three times daily and kept a symptom diary. In the study group, therapy was adjusted weekly by an asthma specialist according to PEF values received daily from the patients. There was no significant difference between the groups in absolute PEF, but PEF variability was significantly smaller in the study group (16.12 +/- 6.93% vs. 27.24 +/- 10.01%, p = 0.049). forced expiratory flow in 1 second (FEV1; % predicted) in the study group was slightly but significantly increased (81.25 +/- 17.31 vs. 77.63 +/- 14.80, p = 0.014) and in the control group, unchanged (78.25 +/- 21.09 vs. 78.88 +/- 22.02, p = 0.497). Mean FEV1 was similar in the two groups both before and after the study. Controls had significantly higher scores for cough (1.85 +/- 0.43 vs. 1.42 +/- 0.28, p < 0.05) and night symptoms (1.22 +/- 0.23 vs. 0.85 +/- 0.32, p < 0.05). There was no significant difference between the groups in daily consumption of inhaled medicine, forced vital capacity, or compliance. Per patient, per week, the additional cost of follow-up by SMS was Euros 1.67 (equivalent to approximately $1.30 per 1 Euro), and SMS transmission required 11.5 minutes. Although a study group of 40 patients is needed for the follow-up study to achieve the power of 80% within the 95% confidence interval, we conclude that SMS is a convenient, reliable, affordable, and secure means of telemedicine that may improve asthma control when added to a written action plan and standard follow-up.", "Cell phone text messaging, via the Short Messaging Service (SMS), offers the promise of a highly portable, well-accepted, and inexpensive modality for engaging youth and young adults in the management of their diabetes. This pilot and feasibility study compared two-way SMS cell phone messaging with e-mail reminders that were directed at encouraging blood glucose (BG) monitoring.\n Forty insulin-treated adolescents and young adults with diabetes were randomized to receive electronic reminders to check their BG levels via cell phone text messaging or e-mail reminders for a 3-month pilot study. Electronic messages were automatically generated, and participant replies with BG results were processed by the locally developed Computerized Automated Reminder Diabetes System (CARDS). Participants set their schedule for reminders on the secure CARDS website where they could also enter and review BG data.\n Of the 40 participants, 22 were randomized to receive cell phone text message reminders and 18 to receive e-mail reminders; 18 in the cell phone group and 11 in the e-mail group used the system. Compared to the e-mail group, users in the cell phone group received more reminders (180.4 vs. 106.6 per user) and responded with BG results significantly more often (30.0 vs. 6.9 per user, P = 0.04). During the first month cell phone users submitted twice as many BGs as e-mail users (27.2 vs. 13.8 per user); by month 3, usage waned.\n Cell phone text messaging to promote BG monitoring is a viable and acceptable option in adolescents and young adults with diabetes. However, maintaining interest levels for prolonged intervals remains a challenge.", "To assess Sweet Talk, a text-messaging support system designed to enhance self-efficacy, facilitate uptake of intensive insulin therapy and improve glycaemic control in paediatric patients with Type 1 diabetes.\n One hundred and twenty-six patients fulfilled the eligibility criteria; Type 1 diabetes for > 1 year, on conventional insulin therapy, aged 8-18 years. Ninety-two patients were randomized to conventional insulin therapy (n = 28), conventional therapy and Sweet Talk (n = 33) or intensive insulin therapy and Sweet Talk (n = 31). Goal-setting at clinic visits was reinforced by daily text-messages from the Sweet Talk software system, containing personalized goal-specific prompts and messages tailored to patients' age, sex and insulin regimen.\n HbA(1c) did not change in patients on conventional therapy without or with Sweet Talk (10.3 +/- 1.7 vs. 10.1 +/- 1.7%), but improved in patients randomized to intensive therapy and Sweet Talk (9.2 +/- 2.2%, 95% CI -1.9, -0.5, P < 0.001). Sweet Talk was associated with improvement in diabetes self-efficacy (conventional therapy 56.0 +/- 13.7, conventional therapy plus Sweet Talk 62.1 +/- 6.6, 95% CI +2.6, +7.5, P = 0.003) and self-reported adherence (conventional therapy 70.4 +/- 20.0, conventional therapy plus Sweet Talk 77.2 +/- 16.1, 95% CI +0.4, +17.4, P = 0.042). When surveyed, 82% of patients felt that Sweet Talk had improved their diabetes self-management and 90% wanted to continue receiving messages.\n Sweet Talk was associated with improved self-efficacy and adherence; engaging a classically difficult to reach group of young people. While Sweet Talk alone did not improve glycaemic control, it may have had a role in supporting the introduction of intensive insulin therapy. Scheduled, tailored text messaging offers an innovative means of supporting adolescents with diabetes and could be adapted for other health-care settings and chronic diseases." ]

[ "9381772", "15262244", "15895892", "11407078", "15599642", "15088306", "9663358", "10509850", "14508044", "16242361", "12851342", "11822921", "10461471", "12421996", "8774159", "9219678", "16416102", "15331394", "8403580", "12127830", "16342083", "8689462", "11302304", "8689457", "3310017", "16206349", "9175299", "12410458", "12951310", "14760806", "1934686", "8886085", "3063436", "15487709", "15449510", "14999424", "12202120", "7944639", "11548229", "12740676", "10870655", "12918884", "12893153", "15776267" ]

[ "[Mechanism of action of hyaluronic acid in gonarthrosis of both knee joints in a right/left comparison. Study with dynamometry, oxygen partial pressure, temperature and Lequesne score].", "Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee.", "Comparison of two hyaluronan drugs in patients with advanced osteoarthritis of the knee. A prospective, randomized, double-blind study with long term follow-up.", "Intra-articular hyaluronan injections for the treatment of osteoarthritis of the knee: a randomized, double blind, placebo controlled study.", "Hylan G-F 20 efficacy on articular cartilage quality in patients with knee osteoarthritis: clinical and MRI assessment.", "A double blind, randomized, multicenter, parallel group study of the effectiveness and tolerance of intraarticular hyaluronan in osteoarthritis of the knee.", "Viscosupplementation with hylan G-F 20: a 26-week controlled trial of efficacy and safety in the osteoarthritic knee.", "The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of hylan G-F 20 and a lower-molecular-weight hyaluronan.", "Re: Karlsson et al. Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study.", "A double-blind randomized controlled trial comparing alternate forms of high molecular weight hyaluronan for the treatment of osteoarthritis of the knee.", "Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee. A prospective, randomized trial.", "Effects of hyaluronate sodium on pain and physical functioning in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial.", "Hyaluronic acid in the treatment of osteoarthritis of the knee.", "Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study.", "Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan Multicentre Trial Group.", "Arthroscopic evaluation of potential structure modifying activity of hyaluronan (Hyalgan) in osteoarthritis of the knee.", "A comparison of two different intra-articular hyaluronan drugs and physical therapy in the management of knee osteoarthritis.", "Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis.", "Intra-articular treatment with hyaluronic acid in osteoarthritis of the knee joint: a controlled clinical trial versus mucopolysaccharide polysulfuric acid ester.", "A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results.", "Preliminary results of integrated therapy for patients with knee osteoarthritis.", "Intra-articular hyaluronic acid compared to intra-articular triamcinolone hexacetonide in inflammatory knee osteoarthritis.", "Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. ORTHOVISC Study Group.", "The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone.", "Intra-articular treatment with sodium hyaluronate in gonarthrosis: a controlled clinical trial versus placebo.", "Clinical effects of intraarticular injection of high molecular weight hyaluronan (Orthovisc) in osteoarthritis of the knee: a randomized, controlled, multicenter trial.", "The double-blind test of sodium hyaluronate (ARTZ) on osteoarthritis knee.", "[Cross-linked hyaluronic acid in the treatment of osteoarthritis of the knee--results of a prospective randomized trial].", "Prospective randomized study comparing the medicoeconomic benefits of Hylan GF-20 vs. conventional treatment in knee osteoarthritis.", "A randomized, single-blind comparison of the efficacy and tolerability of hylan G-F 20 and triamcinolone hexacetonide in patients with osteoarthritis of the knee.", "Intra-articular treatment of knee osteoarthritis. A comparative study between hyaluronic acid and 6-methyl prednisolone acetate.", "High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial.", "Clinical trial of intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee.", "Effects of different hyaluronic acid products on synovial fluid levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in knee osteoarthritis.", "Intra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter, double-blind study.", "Does hyaluronan affect inflammatory cytokines in knee osteoarthritis?", "Efficacy of intraarticular hyaluronic acid in patients with osteoarthritis--a prospective clinical trial.", "Intra-articular injections of 750 kD hyaluronan in the treatment of osteoarthritis: a randomised single centre double-blind placebo-controlled trial of 91 patients demonstrating lack of efficacy.", "Intra-articular hyaluronic acid in osteoarthritis of the knee: an investigation into mechanisms of action.", "Comparison of two different viscosupplements in knee osteoarthritis -- a pilot study.", "Intra-articular treatment with hyaluronic acid. Comparative study of Hyalgan and Adant.", "A one-year, randomised, placebo (saline) controlled clinical trial of 500-730 kDa sodium hyaluronate (Hyalgan) on the radiological change in osteoarthritis of the knee.", "A prospective randomised trial comparing intra-articular Hyalgan injection and arthroscopic washout for knee osteoarthritis.", "Intra-articular hyaluranic acid compared with progressive knee exercises in osteoarthritis of the knee: a prospective randomized trial with long-term follow-up." ]

[ "In a controlled prospective randomized study we evaluated the effectiveness of intraarticular injected hyaluronic acid regarding the changes in the parameters dynamometry, synovial oxygen partial pressure, intraarticular temperature and the knee joint function (Lequesne score). We examined 18 patients with osteoarthritis in both knee joints (Kellgren classification II or III according to x-ray) in right/left comparison. The evaluated parameters were measured before and after a 5-week treatment phase with 5 intraarticular injections (one injection per week). With regard to the efficacy results changes in dynamometric measurement for flexion and extension (for all angular velocities) and Lequesne-score indicate a marked improvement after treatment with hyaluronic acid. The differences between treated and untreated knee were significant. In extension the p-value was 0.0008 and in flexion p = 0.0015. The p-value of the Lequesne-index between the verum and control group was p = 0.0002. After treatment values for oxygen pressure were higher than at baseline and for the intraarticular temperature a small decrease at the end of the treatment phase was documented. The intraarticular injection of hyaluronic acid is effective and safe in the treatment of patients with gonarthrosis. The treatment resulted in a functional improvement of the knee joint and had a good pain-lowering effect in patients suffering from gonarthrosis.", "Non-animal stabilized hyaluronic acid (NASHA) is a novel hyaluronan (HA) preparation with a 4-week intra-articular half-life. This study compared the efficacy of a single injection of NASHA with placebo in patients with osteoarthritis (OA) of the knee.\n This was a 26-week randomized, double-blind, multicenter study of a single intra-articular knee injection with either NASHA or placebo (saline). Assessments included the Western Ontario McMasters Universities osteoarthritis index (WOMAC, Likert Scale) and patients' overall global disease status. A positive response was defined as a reduction in WOMAC pain score for the study knee of 40% from baseline with a minimum improvement of > or =5 points.\n A total of 346 (NASHA 172; placebo 174) patients were treated. WOMAC scores and quality of life were improved in both the NASHA and placebo groups. For the overall population, there were no statistically significant between-group differences in response rates for any efficacy parameters. In patients with OA confined to the knee (N=216), a greater response to NASHA than placebo was observed at week 6 (P=0.025). There were few treatment-related events.\n NASHA was not superior to placebo for the primary efficacy analysis. However, these data may be confounded by the inclusion of patients with OA at other sites, as significant benefits over placebo were found among patients with OA confined to the knee. Future trials of OA that examine a local therapy might need to consider restricting the study population to those patients having OA of only the signal joint.", "To compare the long-term effects of high and low molecular weight hyaluronic acid (HA) applications in severe (Kellgren Lawrence stage III) osteoarthritis (OA) of the knee.\n In a prospective clinical trial 184 knees (92 patients) with radiographic Kellgren Lawrence stage III OA were randomized to receive either 3 intra-articular high molecular weight HA (Hylan G-F 20) injections or 3 low molecular weight HA (Orthovisc) injections at one-week intervals. Patients were evaluated by the Hospital for Special Surgery (HSS) Knee Score and were followed-up for 12 months.\n The total HSS score in high molecular weight HA patients improved from 71.8+/-11.6 to 86.7+/-11.6 and in low molecular weight HA patients from 66.7+/-11.0 to 86.6+/-9.1 at the end of the trial (p < 0.01). There were no statistically significant differences between the groups and both had improved in all parameters at the latest follow-up (p = 0.000).\n Three intra-articular injections at intervals of 1 week of both HA preparations resulted in a pronounced reduction in pain and improved function as measured by the HSS score during a period of 52 weeks, without complications.", "Hyaluronic acid (HA) polymers have been found to be useful as viscosupplements for the treatment of osteoarthritis (OA) in a number of clinical studies. It appears that HA with high molecular weights (HMW) are more effective than low molecular weight HA polymers.\n A single blind, initial randomized study was conducted involving two randomly selected patient groups, which received injections of either placebo or BioHy, a highly purified HMW HA produced by bacterial fermentation. HA was administered intra-articularly and several functional tests, including pain level, stiffness, and physical function, were used to score efficacy at various intervals throughout the study.\n The results through week 20 indicate that BioHy provides relief for osteoarthritic patients without causing adverse effects, although the study was not sufficiently powered to obtain statistically significant differences between the treatment groups.", "The aim of this study was to investigate the effects of intra-articular hyaluronic acid (HA) on symptoms, functional outcome, and changes in articular cartilage assessed by magnetic resonance imaging (MRI) in patients with knee osteoarthritis. Thirty patients were randomly assigned to treatment with HA (hylan G-F 20, Synvisc) or saline. The treatment group consisted of 20 patients receiving three weekly injections of HA into one or both knees (30 knees). The control group consisted of ten patients receiving three intra-articular injections of 2 ml saline at the same intervals (ten knees). To determine the effectiveness of the HA therapy, all patients were assessed prior to the injections (baseline) and after the 1st, 2nd, 3rd, and 8th weeks. Assessment comprised the following: pain at rest, at night, and on walking using a visual analogue scale (VAS); Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and function scores; 15-m walking time; need for analgesics; and evaluation of treatment by the patients. MRI of patellofemoral (PF) articular cartilage was also examined before and after the course of injections at the 8th week. When compared to placebo, a significant statistical difference was found in all clinical parameters. On MRI, although the difference in the PF joint cartilage quality in the HA group before and after the treatment was statistically significant (p < 0.05), this significance was not detected between the groups after the treatment (p > 0.05). After the HA injections, a significant analgesic effect was seen as early as the 3rd week continuing up to the 8th week and functional improvement was seen at the 8th week. In conclusion, intra-articular injections of HA is an effective choice of treatment in patients with knee osteoarthritis.", "To investigate the efficacy and tolerability of a course of 5 injections of hyaluronan (HA) given at intervals of one week in patients with symptomatic, mild to moderate osteoarthritis (OA) of the knee.\n A double blind, randomized, parallel group, multicenter (17 centers), saline vehicle-controlled study was conducted over 18 weeks. Patients received either 25 mg (2.5 ml) HA in a phosphate buffered solution or 2.5 ml vehicle containing only the buffer by intraarticular injection. Five injections were given at one week intervals and the patients were followed for a further 13 weeks. The Western Ontario McMaster (WOMAC) OA instrument was used as the primary efficacy variable and repeated measures analysis of covariance was used to compare the 2 treatments over Weeks 6, 10, 14, and 18.\n Of 240 patients randomized for inclusion in the study, 223 were evaluable for the modified intention to treat analysis. The active treatment and control groups were comparable for demographic details, OA history, and previous treatments. Scores for the pain and stiffness subscales of the WOMAC were modestly but significantly lower in the HA-treated group overall (Weeks 6 to 18; p < 0.05) and the statistically significant difference from the control was not apparent until after the series of injections was complete. The physical function subscale did not reach statistical significance (p = 0.064). Tolerability of the procedure was good and there were no serious adverse events that were considered to have a possible causal relationship with the study treatment.\n Intraarticular HA treatment was significantly more effective than saline vehicle in mild to moderate OA of the knee for the 13 week postinjection period of the study.", "Hylan G-F 20, which is derived from hyaluronan, is a highly purified, elastoviscous fluid with rheologic properties similar to those of synovial fluid in the knee joints of healthy young persons. The efficacy and safety of viscosupplementation with hylan G-F 20 were evaluated in a multicenter, double-masked clinical study in patients with chronic idiopathic osteoarthritis (OA) of the knee of 1 to 30 years' duration. Three intra-articular injections of 2 mL hylan G-F 20 were administered 1 week apart to 57 knees. The control group (60 knees) received 2 mL of physiologic buffered saline solution at the same intervals. Patients were predominantly female (65%), with a mean age of 62 years and mean weight of 76 kg. Using a visual analogue scale, patients assessed the following clinical variables: pain during weight-bearing, pain at rest during the night, reduction of pain during the most painful movement of the knee, and treatment success. Evaluators also assessed patients' loss of activity while performing difficult daily tasks and treatment success. There was dramatic early improvement in all six variables with hylan G-F 20 beginning after the first injection; the improvement continued through the study end points. The differences between hylan G-F 20 and saline treatment were statistically significant for all outcome measures. In the hylan G-F 20 group, 39% to 56% of patients were free or nearly free of weight-bearing pain 10 to 24 weeks after the last injection. Treatment with saline was less effective, with fewer than 13% of patients free or nearly free of weight-bearing pain. Use of rescue therapy was significantly greater in the saline group than in the hylan G-F 20 group. No adverse events were observed in the injected joint after hylan G-F 20 treatment. These results demonstrate that hylan G-F 20 is effective and well tolerated in the management of chronic idiopathic OA.", "The objective of this 12-week, double-masked, randomized, multicenter study was to compare the elastoviscous properties of a high-molecular-weight viscosupplement, hylan G-F 20 (polymer concentration, 0.8%), with those of a lower-molecular-weight hyaluronan (LMW HA) product (polymer concentration, 1%) and to determine the relationship of elastoviscosity to efficacy in the treatment of patients with osteoarthritis (OA) of the knee. Patients had radiographically confirmed primary idiopathic OA of the knee (Larsen grades I to V) with pain despite other treatments. After a 2-week washout period, 70 patients (73 knees) received three 2-mL intra-articular injections of test solution at 1-week intervals. Thirty-eight patients (38 knees) received hylan G-F 20, and 32 patients (35 knees) received LMW HA. During the 12-week follow-up period, the primary outcome measures assessed by patients (using a visual analogue scale) were weight-bearing pain, most painful knee movement, and overall treatment response; the primary outcome measures assessed by study evaluators were weight-bearing pain and overall assessment of treatment. The dynamic elastoviscous properties of the test solutions were measured on an oscillating Couette-type rheometer. Hylan G-F 20 was more elastoviscous than the LMW HA at all frequencies measured (0.001 to 10 Hz). At the final evaluation, patients who received hylan G-F 20 had significantly better results on all primary outcome measures compared with those who received LMW HA. No systemic adverse events were reported. Local adverse events consisted of pain or swelling, noted in 2 of 38 knees injected with hylan G-F 20, and pain, noted in 1 of 35 knees injected with LMW HA (adverse event rates per injection, 1.8% and 0.9%, respectively). The difference in the incidence of adverse events between groups was not statistically significant. The higher-molecular-weight, more elastoviscous hylan G-F 20 had significantly greater pain-relieving effects than did the lower-molecular-weight, less elastoviscous hyaluronan.", "nan", "To compare the safety and effectiveness of a high molecular weight hyaluronan produced by biological fermentation (Bio-HA) with those of avian-derived hyaluronan that uses cross-linking to achieve high molecular weight (CL-HA).\n This was a prospective, multicenter, randomized, double-blind trial evaluating patients with confirmed osteoarthritis of the knee. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC Index) pain subscale was the primary effectiveness measure (visual analog scale). Both products were administered via three weekly injections, with follow-up evaluations at weeks 3, 6 and 12. Acetaminophen was permitted as rescue medication and quantitated by pill counts.\n Analyses were performed on the intent-to-treat population, defined as all patients receiving at least one injection. Of the 321 patients randomized to treatment, 314 patients (98%) completed the final study assessment. Improvement in the average WOMAC Index pain score was 29.8mm (-61.6%) for Bio-HA and 28.8mm (-54.9%) for CL-HA, meeting the prospective criteria for non-inferiority. For the secondary outcome measures, statistically significant differences favored Bio-HA for the number of patients requiring acetaminophen (P=0.013) and patient global satisfaction evaluations (P=0.03). Local reactions differed between the products in that 15 effusions were reported in 13 CL-HA patients (8.1%) after injection, compared to one effusion (0.6%) after Bio-HA injection (P=0.0015).\n The effectiveness of Bio-HA was not inferior to that of CL-HA. The significantly higher incidence of post-injection effusion in the CL-HA group provides a safety advantage for Bio-HA. These data suggest that Bio-HA has an improved benefit-risk profile compared with CL-HA.", "Although both corticosteroid and hyaluronic acid injections are widely used to palliate the symptoms of knee osteoarthritis, little research involving a comparison of the two interventions has been done. We tested the hypothesis that there are no significant differences between Hylan G-F 20 (Synvisc) and the corticosteroid betamethasone sodium phosphate-betamethasone acetate (Celestone Soluspan) in terms of pain relief or improvement in function, as determined by validated scoring instruments.\n One hundred patients with knee osteoarthritis were randomized to receive intra-articular injection of either Hylan G-F 20 or the corticosteroid, and they were followed for six months. The patients treated with Hylan G-F 20 received one course of three weekly injections. The patients treated with the corticosteroid received one injection at the time of enrollment in the study, and they could request one more injection any time during the study. An independent, blinded evaluator assessed the patients with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), a modification of the Knee Society rating system, and the visual analog pain scale.\n Both the group treated with the corticosteroid and the group treated with Hylan G-F 20 demonstrated improvements from baseline WOMAC scores (a median decrease from 55 to 40 points and from 54 to 44 points, respectively; p < 0.01 for both). The scores according to the Knee Society system did not significantly improve for the patients who received the corticosteroid (median, 58 to 70 points; p = 0.06) or for those who received Hylan G-F 20 (median, 58 to 68 points; p = 0.15). The scores on the visual analog scale improved for patients receiving Hylan G-F 20 (median, 70 to 52 mm; p < 0.01) but not for the patients who received the corticosteroid (median, 64 to 52 mm; p = 0.28). However, no significant differences between the two treatment groups were found with respect to the WOMAC, Knee Society system, or visual analog scale results. Women demonstrated a significant improvement in only one of the six possible outcome-treatment combinations (the WOMAC scale), whereas men demonstrated significant improvements in five of the six outcomes (all measures except the Knee Society rating system).\n No differences were detected between patients treated with intra-articular injections of Hylan G-F 20 and those treated with the corticosteroid with respect to pain relief or function at six months of follow-up. Women demonstrated significantly less response to treatment than men did for both treatments on all three outcome scales. Such significant gender-related differences warrant further investigation.", "Intra-articular hyaluronate sodium is a relatively new therapy for the treatment of osteoarthritis of the knee. This randomized, double-blind clinical trial was conducted at a large primary care medical center to determine the impact of hyaluronate sodium vs conventional therapy on measures of pain, stiffness, and disability at rest and following functionally relevant walking and stepping activities.\n A total of 120 patients (mean age, 67 years) with unilateral grades 1 to 3 medial compartment knee osteoarthritis were randomized to 1 of 4 treatment groups: group 1, 2 mL of hyaluronate sodium at a concentration of 10 mg/mL and placebo (100 mg of lactose); group 2, nonsteroidal anti-inflammatory drugs (NSAIDs) (75 mg of diclofenac and 200 microg of misoprostol) and hyaluronate sodium; group 3, NSAIDs and placebo (2 mL of isotonic sodium chloride solution [saline]); and group 4, placebo (lactose and saline). Intra-articular hyaluronate sodium or saline (2 mL) was administered once weekly over 3 weeks while NSAIDs or lactose were administered twice daily over 12 weeks.\n (1) Western Ontario McMaster Universities Index (WOMAC) global measure of pain, stiffness, and disability; (2) visual analog scale (VAS) scores for pain at rest and following functional walking and stepping activities (self-paced walking and stepping); and (3) functional performance (exercise time, heart rate, and predicted maximum oxygen uptake) at baseline and weeks 4 and 12.\n At week 4, significant improvement in WOMAC scores for pain and disability and VAS score for resting pain was observed in groups 1 to 3 compared with baseline measures. Groups 1 and 2 showed significantly lower self-paced stepping pain, while no change was observed in group 4. At week 12, groups 1 to 3 showed significantly greater improvement in WOMAC pain subscale score and VAS score for resting pain; however, these differences did not vary from week 4. Following self-paced walking and stepping, groups 1 and 2 reported significantly less activity pain, while group 1 showed significantly faster self-paced walking and stepping test results. Groups 1 to 3 improved self-paced walking and stepping time at week 12 compared with baseline measures, while predicted maximum oxygen uptake was significantly higher in the hyaluronate sodium groups 1 and 2 at weeks 4 and 12 compared with baseline measures.\n For resting pain relief, hyaluronate sodium seems to be as effective as NSAIDs. Further, for pain with physical activity and functional performance, hyaluronate sodium may be superior to placebo alone or NSAIDs alone.", "We examined the efficacy, safety and patient satisfaction of intra-articular hyaluronic acid (HA) in patients with osteoarthritis of the knee.\n One hundred patients with mild to moderate osteoarthritis of the knee entered a randomized blind-observer trial of 6 months HA vs placebo. Primary efficacy criteria were pain on walking, measured with a visual analogue scale, and the Lequesne Index.\n For pain on walking, a significant difference in favour of HA was found for completed patients at week 5, the end of the course of injections, and at month 6, the end of the study (P = 0.0087 and P = 0.0049, respectively). Further analysis using the Last Observation Carried Forward (LOCF) also showed a significant benefit favouring HA at month 6 (P = 0.0010). For the Lequesne Index, a significant difference in favour of HA was found at week 5 (P = 0.030) and at month 2 (P = 0.0431), but this was only of borderline significance at month 4 (P = 0.0528). Patients' global assessment of efficacy favoured HA at month 6 (P = 0.012). Improvement in other secondary criteria was generally superior in the HA group compared to placebo both at week 5 and month 6. Adverse events, mainly local injection site reactions, occurred in both groups with equal frequency.\n The study demonstrated that five weekly intra-articular injections of sodium hyaluronate (Hyalgan) were superior to placebo and well tolerated in patients with osteoarthritis of the knee with a symptomatic benefit which persisted for 6 months.", "To compare the efficacy and safety of intra-articular injections of two different hyaluronan preparations and placebo in patients with knee osteoarthritis.\n In a randomized, patient- and observer-blind, placebo-controlled and multicentre trial with parallel groups, 210 patients, aged 60 yr or above, with knee osteoarthritis were included in a per protocol analysis. The patients were treated with three injections, once weekly, of either native high-molecular-weight hyaluronan (Artzal((R))) or cross-linked hyaluronan (Synvisc((R))) or with placebo and were followed for 52 weeks. The primary efficacy measures were weight-bearing pain during study weeks 0-26 and the duration of clinical benefit measured with Kaplan-Meier survival analysis for weeks 0-52. The secondary outcome measures were resting and maximum pain, Lequesne index, WOMAC (Western Ontario and McMaster University Osteoarthritis Index) and SF-36 (Medical Outcomes Study Short Form Health Survey) scores.\n The intra-articular injections produced a significant reduction in weight-bearing pain, resting pain, maximum pain and Lequesne and WOMAC scores after 26 weeks. There were no significant differences in outcome between any of the three study groups during the first 26 weeks. In direct comparison against placebo for weeks 0-52, neither hyaluronan treatment (Artzal or Synvisc) showed a significantly longer duration of clinical benefit than placebo. However, when data for the two hyaluronan-treated groups were pooled, treatment with hyaluronan had a significantly longer duration of benefit compared with placebo (P = 0.047).\n Patients with knee osteoarthritis who were treated by injection into the knee of either of two hyaluronan preparations or placebo showed clinical improvement during the first 26 weeks of treatment, though neither hyaluronan preparation gave a longer duration of clinical benefit than placebo. However, when data for the two hyaluronan treatments were pooled, there was a significantly longer duration of clinical benefit for hyaluronan treatment than for placebo.", "To assess the effects of intra-articular injections of hyaluronan on symptoms of knee osteoarthritis (OA).\n Two hundred and forty patients with symptomatic, radiological knee OA were randomly assigned to treatment with weekly injections for five weeks with either 25 mg of high molecular weight hyaluronan or vehicle. Results were evaluated at weeks 1, 2, 3, 4, 5, 13, and 20 by visual analogue scales (pain, function, motion, activity), algofunctional index, and global evaluation by patient and investigator. Analysis was by \"intention to treat', \"per protocol', and area under the curve principles on unstratified patient groups and for patients stratified into four groups of equal size by age and baseline algofunctional index.\n No serious side effects were reported. At 20 weeks both treatment groups were improved compared with baseline, with no difference between unstratified groups treated with placebo or hyaluronan. Comparison of treatment groups stratified by age and baseline algofunctional index revealed a significant difference in favour of hyaluronan over placebo (pain, activity, algofunctional index, global evaluations by patient and investigator) for patients older than 60 years and with a baseline algofunctional index greater than 10. There was no clinically relevant difference between the two treatments for the other three stratified subgroups of younger age or fewer symptoms. Similar results were obtained by area under the curve, intention to treat, and per protocol analysis.\n Patients older than 60 years with knee osteoarthritis and with significant symptoms corresponding to an index of severity of knee disease of 10 or more, comprise the group most likely to benefit from treatment with intra-articular hyaluronan injections.", "Several reported studies suggest that repeated intra-articular injections of hyaluronan result in sustained relief from pain and functional disability in patients with knee osteoarthritis. Several in vivo data suggest that hyaluronan might have a beneficial structural effect in osteoarthritis. The objective of the study was to evaluate the potential structure-modifying effects of Hyalgan (500-730 kDa molecular weight), a highly-purified sodium hyaluronate.\n Patients with painful knee osteoarthritis (ACR criteria) were enrolled in a prospective, controlled study of 1-year duration. After randomization, either conventional therapy or three cycles (every 3 months) of three intra-articular injections of Hyalgan (once a week during 2 weeks) were given. Clinical outcome was added using pain visual analog score (VAS), functional impairment: Lequesne's index, quality of life: arthritis impact measurement scale (AIMS2) and structural outcome using X-rays: joint space narrowing and arthroscopy: global assessment using VAS, SFA scoring and grading systems.\n Of the 39 recruited patients, 36 completed the 1-year trial (19 in the Hyalgan group and 17 in the control group). There was no difference between groups at entry. Between-group comparison for changes in clinical parameters reached statistical significance for the quality of life index (AIMS2: -0.4 +/- 0.7 vs 0.2 +/- 0.9 in the Hyalgan and control groups respectively, P < 0.05). Deterioration in the structural parameters was less in the Hyalgan group, with a statistically significant difference for two of the three evaluated parameters (overall assessment of chondropathy: +5.1 +/- 12.7 vs 16.7 +/- 18.3, P = 0.016; SFA scoring system: +3.7 +/- 7.3 vs +9.0 +/- 11.5, P = 0.05) in the Hyalgan and control groups, respectively.\n This study supports existing data concerning the favorable symptomatic effect of intra-articular injections of Hyalgan in osteoarthritis of the knee and suggests that repeated intra-articular injections of Hyalgan might delay the structural progression of the disease. Other studies are required to confirm these results and to determine the long-term monitoring of osteoarthritic patients using such local therapy.", "The aim of this study was to compare the effects of physical therapy agents (PTA) and two different intra-articular hyaluronan drugs (sodium hyaluronate (NaHA) and hylan G-F 20) on knee osteoarthritis (OA). The randomised, single-blind study, with 12 months of follow-up, was performed on 80 patients diagnosed as knee OA. The patients were randomly divided into two treatment groups: patients in group 1 were given weekly intra-articular hyaluronan treatment which consisted of either hylan G-F 20 or NaHA during the first 3 weeks and in the sixth month; PTA was applied to each patient in group 2 five times a week for 3 weeks with a series of infrared, short-wave diathermy-pulsed patterns and interferential therapy. Clinical assessments for each patient were made at 1, 3, 6, 9 and 12 months using the following measures: spontaneous pain, pain at rest, pain at night, pain on touch, pain on movement, 15 m walking time, range of motion, short form 36 (SF-36), Western Ontario and McMaster University Osteoarthritis Index (WOMAC) global assessment. There was significant improvement in all variables measured in both groups during the follow-up except the WOMAC-stiffness and range of the motion. The improvement of pain (at night, at rest, SF-36) and SF-36 social functioning subscales was greater in the PTA group. Consequently, in the subgroup analyses, there was no difference between PTA and hylan groups for this improvement. In the comparison of two drugs, the reduction of pain on touch and WOMAC-function was greater in hylan group than that of NaHA. No serious local or systemic effects were observed following injections. Although all patients had improvement, PTA was superior to hyaluronan group for no activity-related pain and functional performance. On the other hand, this study supports the preferential use of hylan over NaHA in patients with knee OA.", "To evaluate long term efficacy of three iterative courses of three weekly intra-articular (IA) injections of NRD101 in the treatment of symptomatic knee osteoarthritis (OA).\n A 1 year prospective, multicentre, randomised, double blind, placebo controlled study of 301 patients aged >50 years with painful and radiological medial knee OA. Patients were randomly assigned into three groups receiving: (1) three courses of three IA injections of hyaluronic acid (HA) + oral placebo; (2) IA injections of saline solution + diacerein 100 mg/day; (3) IA injections of saline solution + oral placebo. Demographic data and symptomatic criteria-pain, Lequesne's index, patient's global assessment of disease activity, percentage of painful days-were obtained during the study; primary structural criterion was JSW. Efficacy criteria were changes in pain VAS, joint space narrowing (JSN), and percentage of progressors (JSN >0.5 mm). An intention to treat analysis was used for symptomatic variables, and completer analysis for structural variables.\n Baseline characteristics were similar between the three groups. Mean (SD) improvement in pain VAS was clinically relevant (-33.9 (27.3), n = 301), but with no difference between the groups (p = 0.96). JSW deteriorated (-0.09 (0.55) mm, n = 277, p = 0.01), but with no difference between the groups (p = 0.82). Percentages of progressors were 17.7, 18.9, and 20.3% (p = 0.90), in groups 1, 2, and 3, respectively.\n A weak but statistically significant structural deterioration occurred over 1 year, together with clinically relevant symptomatic improvement in patients receiving oral drug and iterative IA injections. Symptomatic and/or structural effects for both this new HA compound and diacerein were not demonstrated.", "In a single-blind, randomized clinical trial, both the efficacy and safety of hyaluronic acid (HA) were compared with that of mucopolysaccharide polysulfuric acid ester (MPA) in patients with osteoarthritis of the knee joint. Both agents were administered intra-articularly over six weeks. Patients received either seven injections of HA or 13 injections of MPA. Joint function, range of motion, severity of pain, the general condition of the bony structure and soft tissue of the joint area, and the global clinical efficacy and safety of the medication were assessed. The mean improvement in the modified total Larson rating score was 22% (SD = 28) after HA treatment and 7% (SD = 17) after treatment with MPA (analysis of variance: p = 0.02). This change was mainly caused by a reduction of pain. The onset of pain relief was more rapid in the HA group. The therapeutic effect increased in both treatment groups during the follow-up period. During this interval, lasting six months after the start of treatment, a further reduction of pain and an improvement of knee joint function could be observed. At the end of the study, 25 out of 33 (76%) patients in the HA group and 11 out of 24 (46%) patients in the MPA group were symptom-free or markedly improved (Chi-square test: p = 0.02). Both agents were tolerated very well.", "First, to assess the clinical effectiveness of hylan G-F 20 in an appropriate care treatment regimen (as defined by the American College of Rheumatology (ACR) 1995 guidelines) as measured by validated disease-specific outcomes and health-related quality of life endpoints for patients with osteoarthritis (OA) of the knee. Second, to utilize the measures of effectiveness and costs in an economic evaluation (see accompanying manuscript).\n A total of 255 patients with OA of the knee were enrolled by rheumatologists or orthopedic surgeons into a prospective, randomized, open-label, 1-year, multi-centred trial, conducted in Canada. Patients were randomized to 'Appropriate care with hylan G-F 20' (AC+H) or 'Appropriate care without hylan G-F 20' (AC). Data were collected at clinic visits (baseline, 12 months) and by telephone (1, 2, 4, 6, 8, 10, and 12 months).\n The AC+H group was superior to the AC group for all primary (% reduction in mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale: 38% vs 13%,P =0.0001) and secondary effectiveness outcome measures. These differences were all statistically significant and exceeded the 20% difference between groups set a priori by the investigators as the minimum clinically important difference. Health-related quality of life improvements in the AC+H group were statistically superior for the WOMAC pain, stiffness and physical function (all P< 0.0001), the SF-36 aggregate physical component (P< 0.0001) and the Health Utilities Index Mark 3 (HUI3) overall health utility score (P< 0.0001). Safety (adverse events and patient global assessments of side effects) differences favoured the AC+H group.\n The data presented here indicate that the provision to patients with knee OA of viscosupplementation with hylan G-F 20 within an appropriate care treatment regimen provides benefits in the knee, overall health and health related quality of life at reduced levels of co-therapy and systemic adverse reactions.\n Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.", "To investigate the effects of integrated therapy on the functional status of patients with knee osteoarthritis (OA).\n A total of 140 subjects with bilateral knee OA (Altman grade II) were randomized sequentially into 4 groups (groups I-IV). Group I received isokinetic exercises; group II received isokinetic exercise and pulse ultrasound for periarticular soft tissue pain; group III received isokinetic exercise, pulse ultrasound, and intraarticular hyaluronan therapy; and group IV acted as the control group. The therapeutic effects of the interventions were evaluated by changes in Lequesne's index, knee range of motion, peak muscle torques of knee flexion and extension, and ambulation speed after 8 weeks of treatment and at followup 1 year later. In addition, changes in visual analog scale pain and rates of attrition in each group were also recorded.\n Patients in groups I-III exhibited increased muscle peak torques and significantly reduced pain and disability after treatment and at followup. Groups II and III showed significant improvements in range of motion and ambulation speed after treatment. Group III also showed the greatest increase in walking speed and decrease in disability after treatment and at followup. Both group II and group III had significant gains in muscular strength after treatment and at followup; group III showed the greatest gains.\n An integrated therapy deals with the extra- and intraarticular progressive pathologic changes, and kinesiologic management of OA is suggested for the management of knee OA.", "The aim of this study was to determine the comparative efficacy and safety of intra-articular (i/a) triamcinolone. hexacetonide (TH) and i/a hyaluronic acid (HA) in inflammatory knee osteoarthritis. A randomized double-blind comparative trail was carried out in a rheumatology outpatient department. There were 63 patients (24 male, 39 female, mean age 70.5 years) with bilateral symptomatic knee osteoarthritis with effusion. Each was given five HA injections at weekly intervals; or 20 mg TH followed by four placebo (saline) injections. Patients were examined weekly during the treatment period and then at monthly intervals for a further 6 months. Assessment included recording of: visual analog scores (VAS) for pain; duration of stiffness; range of movement; joint effusion; local heat; synovial thickening; joint-line and periarticular tenderness. The principal outcome measure was pain on a self-selected activity assessed by Vas. The two groups were comparable at entry and no significant differences between the groups developed at any time during the treatment period. However, there was a high drop-out rate and intention to treat analysis failed to demonstrate statistically significant differences between the groups. In patients remaining in the study, significantly less pain was experienced by the HA group during the 6 month follow-up period. Other parameters showed a similar trend in favor of experienced by the HA group during the 6 month follow-up period. Other parameters showed a similar trend in favor of HA. We could not, however, demonstrate significant differences between the placebo and active treatments. HA may therefore be a useful additional therapy for symptomatic knee osteoarthritis and may have a long duration of action.", "A prospective, multicenter, randomized, double-blind, controlled trial was conducted in 226 patients with knee osteoarthritis to evaluate the safety and efficacy of intraarticular injections of sodium hyaluronate. Patients were randomized to three weekly injections of 30 mg sodium hyaluronate or physiologic saline (control) and were observed for an additional 25 weeks. In comparison with the control group, among patients who completed at least 15 weeks of the study and whose Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was less than 12 at baseline, sodium hyaluronate injection resulted in improvement in Western Ontario and McMaster Universities Osteoarthritis Index pain score, patient and investigator global assessments, and pain on standing from Weeks 7 to 27. Fifty-eight percent of patients treated with sodium hyaluronate achieved a 5-unit or greater improvement in mean pain score from Weeks 7 through 27, compared with 40% of control patients. In addition, nearly twice as many patients treated with sodium hyaluronate as with saline (30% versus 17%, respectively) achieved a net improvement of at least 7 units. In contrast to treatment with saline, Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was inversely related to the magnitude of improvement after treatment with sodium hyaluronate. Few side effects were attributed to treatment, and no differences between treatment groups were seen in this respect (sodium hyaluronate, nine [8%]; saline, 11 [10%]). The incidence of injection site reactions was low (sodium hyaluronate, 1.2 %; saline, 1.5%). The results indicate that sodium hyaluronate treatment is well tolerated and produces statistically and clinically significant improvement of symptoms in patients with mild to moderate knee osteoarthritis in whom pain in the contralateral knee is relatively modest.", "To determine the safety and efficacy of viscosupplementation with hylan G-F 20, a cross-linked hyaluronan preparation, used either alone or in combination with continuous non-steroidal anti-inflammatory drug (NSAID) therapy, a randomized, controlled, multicenter clinical trial, assessed by a blinded assessor, was conducted in 102 patients with osteoarthritis (OA) of the knee. All patients were on continuous NSAID therapy for at least 30 days prior to entering the study. Patients were randomized into three parallel groups: (1) NSAID continuation plus three control arthrocenteses at weekly intervals; (2) NSAID discontinuation but with three weekly intra-articular injections of hylan G-F 20; and (3) NSAID continuation plus three injections, one every week, intra-articular injections of hylan G-F 20. Outcome measures of pain and joint function were evaluated by both the patients and an evaluator at baseline and weeks 1, 2, 3, 7 and 12, with a follow-up telephone evaluation at 26 weeks. At 12 weeks all groups showed statistically significant improvements from baseline, but did not differ from each other. A statistical test for the equivalence, the q-statistic, demonstrated that viscosupplementation with hylan G-F 20 was at least as good or better than continuous NSAID therapy for all outcome measurements except activity restriction. At 26 weeks both groups receiving hylan G-F 20 were significantly better than the group receiving NSAIDs alone. A transient local reaction was observed in three patients after hylan G-F 20 injection; only one patient withdrew from the study as a result and all recovered without any sequela. Hylan G-F 20 is a safe and effective treatment for OA of the knee and can be used either as a replacement for or an adjunct to NSAID therapy.", "A double-blind, placebo-controlled study was carried out in 34 patients suffering from osteo-arthritis of the knee. A total of 40 joints was treated at random with 3 intra-articular injections, at 1 week intervals, of either 20 mg sodium hyaluronate or placebo. Clinical examinations, including assessments of spontaneous pain intensity, pain on touch, under load and while walking, were made before each injection and repeated 7 days after the last one and again at 60 days after the start of the trial. The results showed a significant difference between treatments for all the variables assessed. In the sodium hyaluronate group, pain relief was not only rapid but also long lasting. Local tolerance was very good for both treatments.", "To evaluate the efficacy and safety of injection of high molecular weight (HMW) hyaluronan (Orthovisc) in patients with mild, moderate, and severe knee osteoarthritis (OA).\n A randomized, arthrocentesis-controlled, multicenter trial. Patients (n = 372) were randomized to 4 weekly HMW hyaluronan injections (O4, n = 128), 3 weekly HMW hyaluronan injections followed by one arthrocentesis (O3A1, n = 120), or 4 arthrocenteses without injection (control group, A4, n = 124). All patients had knee OA, as determined by Kellgren-Lawrence (K-L) grade, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score > or = 200 mm and < 400 mm in index knee and < 150 mm in contralateral knee. The primary outcome measure was the proportion of patients achieving a 20% relative and 50 mm absolute improvement from baseline in WOMAC pain score at Weeks 8, 12, 16, and 22 post-baseline in the index knee. Secondary outcomes were Patient Global score, Investigator Global score, and Pain on Standing score.\n The evaluable subgroup consisted of patients with K-L grade 2 or 3 at baseline. The comparison of O4 versus A4 for the primary outcome approached, but did not reach, significance in the evaluable subgroup: 76% of O4 patients had > or = 20% improvement in WOMAC pain score at Week 8 compared to 62% of A4 patients. More O4 patients had > or = 40% improvement in WOMAC pain score compared to A4. The effectiveness of the 3-injection regimen (O3A1) was masked by a possible placebo effect from the needle injection procedure in the A4 (control) group. No differences between groups were observed with respect to incidence of adverse events.\n Our findings indicate that HMW hyaluronan is safe and seems to be effective in the treatment of mild to severe OA of the knee.", "At this time, no definite treatment exists for osteoarthritis disease. Hyaluronate (ARTZ) is one of the most important components of synovial fluid. It is generally accepted that hyaluronic acid protects the articular cartilage and soft tissue surfaces from trauma during joint function.\n Ninety patients with 116 knees diagnosed as early arthritis (mild to moderate) by four senior orthopaedic surgeons were selected to join this study. The trial design was applied with a double-blind model. The selected patients were randomly injected with 2.5 ml drugs (ARTZ or placebo) intra-articularly once a week for five consecutive weeks without the use of local anesthetic drugs. Evaluation results included grading of subjective and objective symptoms and daily activities. The follow-up period was up to six months after initial injection.\n According to the results of clinical evaluation and statistical analysis, SPH (ARTZ) is quite effective for osteoarthritis knees, and significantly better than the placebo. The effective peak was one week after five injections of ARTZ. The effective period could last up to three months without additional treatment. The efficacy of ARTZ on osteoarthritis knees was more prominent for relief of motion pain and improvement of knee movement. No side effects developed during a six month period.\n Based on clinical results here, SPH is a safe drug for administration as an alternative approach to treat the osteoarthritis knee.", "The objective of this trial was to compare the effectiveness of intraarticular injection of highly cross-linked hyaluronic acid (HA) with intraarticular injection of gaseous oxygen (O 2 ) in patients with clinical symptoms of cartilage damage in the knee.\n Based on arthroscopically verified diagnosis, 111 patients were randomised and treated prospectively either with HA or O 2. The treatment was completed with an exercise program. The follow up was one year. 109 patients (56 x HA, 53 x O 2 ) were statistically calculated with the Wilcoxon-test according to the results of the Lysholm-score, the Tegner-activity-index, the Womac-score for pain, stiffness, function and the VAS for pain in rest and under strain.\n Both treatments were able to attain a statistically significant reduction of pain (VAS in rest and under strain, Womac part A), a reduction of joint stiffness (Womac part B) and improvement of joint function (Womac part C, Lysholm-score) during the follow up of one year. The Tegner-activity-index showed no significant change under both treatments. The comparison of both treatments showed differences in VAS under strain (p = 0.001), the Lysholm-score (p = 0.003), Womac part A (p = 0.003) and part C (p = 0.001). As a result HA showed significant better improvements with the VAS and Lysholm-score and oxygen showed significant better changes in the Womac-score part A and C. The results with cartilage damage 2 degrees were the same as in the total (VAS strain: p = 0.029 for O 2, Lysholm-score: p = 0.003 for HA, WOMAC part A: p = 0.009 for HA, Womac part C: p = 0.006 for O 2 ). The results with cartilage damage 3 degrees showed significant differences in reduction of joint stiffness (Womac part B: p = 0.012) for O 2. For cartilage damage 4 degrees HA showed significant reduction of pain (VAS rest: p = 0.001, VAS strain: p = 0.003) and O 2 significant reduction of pain and function (Womac part A: p = 0.004, part C: p = 0.002).\n Both methods are suitable to improve significantly the discomfort due one year to osteoarthritis. The pain relief by HA and the improvement of joint function by O 2 treatment have been shown for higher degrees of cartilage damage.", "In a previous study, we determined the costs over 6 months to the French public health insurance system of Hylan GF-20 (Synvisc) in 66 patients with knee osteoarthritis. Here, we compared the medicoeconomic benefits over 9 months in 506 patients given Hylan GF-20 or conventional treatment for knee osteoarthritis.\n This prospective randomized study was conducted from October 1998 to February 2000. Clinical status was evaluated using the Lequesne index, the WOMAC index, and the SF12 quality-of-life questionnaire. Medical and sick leave costs to the public health insurance system were determined.\n Effectiveness criteria were evaluable in all 506 patients. Significant clinical improvements were noted from the first month to the end of the 9-month study period in the Synvisc group. A mean 2-point difference in the Lequesne index area-under-the-curve was found in favor of Synvisc (P < 0.0001). Mean medical and sick leave costs per patient over 9 months were 829.10 in the Synvisc group and 829.40 in the conventional treatment group.\n This study carried out over 9 months in a large population confirms that Synvisc viscosupplementation is more effective than conventional treatment, at no additional cost. It takes a step toward answering the request of international experts for medicoeconomic data on viscosupplementation for osteoarthritis.", "To assess prospectively the efficacy and tolerability of hylan G-F 20 (HG-F 20; Synvisc) and intraarticular triamcinolone hexacetonide (TH; Aristospan) for treatment of osteoarthritis (OA) knee pain in a 26 week, randomized, multicenter, evaluator-blind study.\n Patients with OA were treated with typical regimens of HG-F 20 (n = 113) and TH (n = 102). Primary assessments were the WOMAC question A1 (pain walking on a flat surface), and a 100 mm visual analog scale (VAS) for patient and investigator overall assessments. Total WOMAC and WOMAC domain C (function) scores were also assessed. The intent-to-treat population was analyzed using a last-observation carried forward approach.\n Maximum pain relief occurred at 1-2 weeks for TH and at Week 12 for HG-F 20. At Weeks 12 and 26, HG-F 20 was significantly better than TH for the WOMAC question A1 responses (p = 0.0071 and p = 0.0129, respectively), and patient VAS (p < 0.0001 and p < 0.0001) and investigator VAS (p < 0.0300 and p = 0.0004) assessments. Similar significant (p < 0.01) results were observed at Weeks 12 and 26 for total WOMAC and domain C scores. While 15 TH-treated patients discontinued the study due to lack of efficacy, none did so with HG-F 20 treatment (p < 0.01). Both agents were well tolerated with similar adverse event profiles.\n Viscosupplementation with HG-F 20 resulted in a longer duration of effect than TH with a comparable tolerability profile. These data support the preferential use of HG-F 20 over TH for treatment of chronic OA knee pain.", "The efficacy and tolerability of 20 mg of hyaluronic acid were compared in an open, randomized trial with that of 40 mg of 6-methylprednisolone acetate, administering them both by an intra-articular route once a week for 3 weeks to patients suffering from inflammatory knee osteoarthritis. The results of the study showed that for up to one week after the end of treatment hyaluronic acid's analgesic activity was comparable to that of the steroid, while at the end of the follow-up (45 days after the end of treatment) all the pain monitoring parameters presented significant differences in favour of the HA-treated group. Both treatments were well tolerated, since no local or systemic adverse reactions were observed.", "Hyaluronic acid is a natural component of cartilage and is considered not only as a lubricant in joints but also as playing a physiological role in the trophic status of cartilage. Hyalectin, a selected fraction of hyaluronic acid extracted from cocks' combs, has exhibited efficacy in animal models of osteoarthritis. To assess the efficacy and tolerability of intra-articular injections of hyalectin, we conducted a prospective, randomized, placebo-controlled trial of 1 years' duration in 110 patients with painful hydarthrodial osteoarthritis of the knee. At entry and once a week for 3 weeks, aspiration of the knee effusion and intra-articular injections of either hyalectin 20 mg (H) or its vehicle (C) were performed. The vehicle acted as the control treatment. Four weeks after the last injection, the improvement was greater in the H group compared with the C group (pain: -35.5 +/- 26.4 mm vs -25.8 +/- 21.4, P = 0.03, Lequesne's functional index: -3.8 +/- 4.3 vs -2.3 +/- 3.3, P = 0.03). During the 1 year follow-up, the need to perform supplementary local therapies (joint fluid aspiration because of painful hydarthrodial episodes and/or local corticosteroid injections) was more frequent in group C (44% vs 30%, P = 0.03). Moreover, at the final visit, the physician's overall assessment of efficacy was in favor of H (77% vs 54%, P = 0.01) and the improvement in the functional index was greater in group H (-4.4 +/- 5.1 vs -2.7 +/- 4.1, P = 0.05). This study suggests that intra-articular injections of hyalectin may (1) improve clinical condition and (2) have a long-term beneficial effect in patients with osteoarthritis of the knee.", "A multi-centre randomized, double-blind, parallel-group clinical trial was carried out in 63 patients with osteoarthritis of the knee to compare the efficacy and tolerability of a course of intra-articular injections of 20 mg sodium hyaluronate with a similar course of injections of placebo. Treatment consisted of up to 11 injections over a 23-week period. Evaluation was by means of subjective symptom and activity assessments, serially during the course of treatment and also 25 weeks thereafter. Ten patients (5 of 30 on active treatment; 5 of 33 on placebo) were withdrawn prematurely. Pain on movement, assessed by visual analogue scale (VAS) showed statistically significant (p less than 0.05 to p less than 0.0001) reductions in mean scores throughout the first 11 weeks of treatment with sodium hyaluronate but smaller, non-significant, reductions with placebo treatment. The difference between treatments was significant (p less than 0.05) at 5 weeks. Pain at rest, also assessed by VAS, showed little change in mean scores with placebo but with sodium hyaluronate there was a progressive reduction which was significant (p less than 0.01) throughout the period from 5 to 23 weeks. The difference between sodium hyaluronate and placebo was significant (p less than 0.05 to p less than 0.002) at Weeks 5, 11, 15, 19 and 23. 'Activities of daily living' were assessed using a standard scale. There were small improvements with both treatments, significant at some assessments and somewhat greater with sodium hyaluronate than placebo, but there were no statistically significant differences between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "The aim of this study was to evaluate the effects of different hyaluronic acid (HA) forms on synovial fluid levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during the treatment of patients with knee osteoarthritis (OA). Forty patients were randomly assigned to 2 groups that were treated with native sodium hyaluronate (group I) or cross-linked hylan G-F 20 (group II). Clinical evaluations and synovial fluid aspirations were performed before the 1st injection (baseline), the 2nd injection (week 1), the 3rd injection (week 2), and at 1 week after the 3rd injection (week 3). Synovial fluid levels of both ICAM-1 and VCAM-1 were significantly reduced at weeks 1 to 3, compared to the baseline values. The Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index was used for clinical evaluations; the WOMAC pain score and physical function score were progressively improved at weeks 1 to 3 in both groups; the WOMAC stiffness score was significantly improved at week 3 in both groups. No significant differences were noted between the 2 treatment groups in respect to ICAM-1 levels, VCAM-1 levels, WOMAC pain score, stiffness score, or physical function score at any time. The decreased ICAM-1 and VCAM-1 levels after intra-articular HA injection may help to explain the anti-inflammatory effects of HA therapy in knee OA.", "The efficacy and the safety of intra-articular injections of sodium hyaluronate were studied in patients with osteoarthritis of the knee in a randomized multicenter double-blind study. Two hundred and nine patients received five injections of either 25 mg hyaluronate/2.5 ml (verum, N = 102) or 0.25 mg hyaluronate/2.5 ml (control, N = 107) at weekly intervals. Seven patients in each group were excluded from the protocol-correct efficacy analysis. The Lequesne Index, the first main criterion, showed a significant superiority of the verum-treated patients after the third injection up to the final follow-up examination 9 weeks after the last injection (MANOVA, P < 0.025). The consumption of paracetamol was defined as a complementary main criterion that did not reveal significant differences between the treatment groups. Most of the individual secondary endpoints demonstrated a much better response to the active treatment without reaching the significance level in the intergroup comparisons for the single time-points. Side-effects were confined to local reactions of minor severity and short duration in four patients (six events) of the verum group and in five patients of the control group. Clinical chemistry and hematology remained essentially unchanged.", "Our aim was to investigate the effects of hyaluronan on inflammatory cytokines in the synovial fluid of patients with knee osteoarthritis. The study was single blind, placebo-controlled, and randomized. We administered hyaluronan to 22 patients in the study group and placebo to 19 in the control group. Enzyme-linked immunosorbent assay was used to determine the levels of cytokines. Both HA and placebo caused a significant decrease in interleukin (IL)-6 levels (P=0.0001 and P=0.04, respectively). But it was more significant in the study group. However, IL-8 and tumor necrosis factor alpha (TNF-alpha) levels did not change in either group (P>0.05). The amount of effusion decreased significantly in the study group (P=0.001) but not in the control group (P=0.133). It can be concluded that hyaluronan considerably decreased IL-6 levels, which correlated with clinical improvement, but had no effect on IL-8 and TNF-alpha levels in synovial fluid. However, larger studies with longer follow-up periods are needed to explain the effect of hyaluronan on cytokines.", "The goal of this study was to determine whether or not the intraarticular administration of hyaluronic acid can improve functional parameters, such as isokinetic muscle strength or total work and clinical test results in patients with osteoarthritis (OA) of the knee.\n As part of a prospective, controlled study 43 patients with osteoarthritic changes of both knees (radiographic Kellgren stage II-III) were followed in a right/left comparison. The influence of intraarticularly injected hyaluronic acid (20mg hyaluronic acid/2ml Hyalart) on functional and clinical parameters was analysed. We used the isokinetic system Cybex 600 for measuring maximal isokinetic muscle strength and total work. A total of 20 males and 23 females fulfilled the inclusion criteria with an age between 55-78 years and underwent five injections of hyaluronic acid (one injection per week). The injected knee represented the treatment group, while the contralateral knee served as the control.\n The maximum peak torque of the knee extensors in the treatment group was measured between 57+/-26.15/32.33+/-19.63Nm prior to the injections and 77.17+/-32.54/47.83+/-21.43Nm following the hyaluronic acid therapy (P< 0.01). The analysis of the knee flexors at angular velocities of 60 degrees /s and 180 degrees /s revealed values of 40.44+/-21.58/22.89+/-16.64Nm and 53.55+/-24.26/34.05+/-17.37Nm (P< 0.01) respectively. The evaluation of the total work of the knee flexors and extensors revealed a significant difference (P< 0.01) between the treatment and control group. The Lequesne score was reduced from 13.57+/-1.88 prior to the injections to 7.94+/-2.53 after the treatment (P< 0.01). The pain score was documented with the help of a visual analog scale. The VAS values were reduced at rest from 3.83+/-1.72cm to 1.36+/-1.42cm and during weight bearing from 7.57+/-1.34cm to 3.75+/-1.32cm in the treatment group (P< 0.01).\n This controlled prospective clinical trial confirmed that 5 weekly intraarticular injections of HA (Hyalart) in patients with OA of the knee provide pain relief and functional improvements.\n Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.", "To determine the safety and efficacy of intra-articular injections of hyaluronan in the treatment of osteoarthritis of the knee.\n A randomised double-blind placebo-controlled trial was carried out on 91 patients with radiologically confirmed osteoarthritis of the knee who were recruited from the outpatient clinics.\n It was found that weekly intraarticular injections of 20 mg of hyaluronan of M(r) = 750,000 (Hyalgan) in 2 ml of buffered saline performed no better than the inert vehicle alone over a five week period. The principal side effects of a transient increase in pain and swelling in the affected knee was observed in 47% of the treatment group compared with 22% of the placebo group. A few patients with radiologically mild disease treated with Hyalgan appeared to experience medium to long-term symptomatic improvement over matched placebo controls as judged by a delayed return to previous NSAID therapy or analgesia other than paracetamol. Patient numbers in the survival groups, however, were too small to be meaningful.\n It is concluded that intraarticular administration of this preparation of 750 kD hyaluronan offers no significant benefit over placebo during a five week treatment period, but incurs a significantly higher morbidity, and therefore has no place in the routine treatment of osteoarthritis.", "The objective of this study was to investigate mechanisms of action of intra-articular hyaluronic acid in osteoarthritis (OA) of the knee. Twelve patients with bilateral knee OA and synovial effusions entered a randomized, single-blind, blind observer study. Hyaluronic acid (\"Hyalgan\", Fidia SpA, Italy) or placebo were given by intra-articular injection weekly for 5 weeks. Assessments included clinical indices and imaging (magnetic resonance imaging (MRI) and 99m Tc bone scanning) before and after the course of injections. In addition, synovial fluid keratan sulfate (KS), chondroitin sulfate (CS) and C-propeptide of type II collagen (CPII) were measured. MRI and 99m Tc scanning showed no change in either treated or placebo knees over the 6-week study period. A fall in KS levels occurred in treated knees compared with placebo (Wilcoxon paired test, P = 0.1), although this did not reach significance perhaps due to small sample numbers). Ten out of 12 treated knees showed a fall in KS, compared with four out of 12 placebo knees. CS and CPII levels did not change significantly. Intra-articular injection of hyaluronic acid did not result in any improvement in the clinical indices compared to the placebo. In conclusion, assessment of cartilage markers may be of value when studying novel therapies in OA. MRI appearances remain remarkably stable over a 6-week period.", "A pilot study was designed to investigate the efficacy of two different hyaluronic acid preparations combined to physical therapy in patients with knee osteoarthritis in terms of reduction in pain and disability and muscle strengthening. Thirty-seven patients with symptomatic osteoarthritis of the knees were randomly assigned into three groups. First group received a lower molecular weight hyaluronic acid plus physical therapy, second group received a higher molecular weight hyaluronic acid plus physical therapy, and the third group received physical therapy alone. The isokinetic knee muscle strengths and index of severity for osteoarthritis of the knee scores were evaluated at baseline, at the end of treatment (3 weeks) and at 3 months of follow up. At both short-term (3 weeks) and long-term (3 months) evaluations, index of severity for osteoarthritis of the knee scores were reduced in all three groups, while there was no significant muscle strengthening.", "Forty-nine patients diagnosed as having gonarthrosis were given intra-articular treatment with hyaluronic acid (Adant or Hyalgan) in a blind randomised study. We concluded that the efficacy with Adant at 3 months after treatment was greater than with Hyalgan (50% versus 21.1%). The maximum improvement with hyaluronic acid was seen at 5 weeks in 75.4% and the adverse effects consisted of pain in the infiltration side which was almost twice as great with Adant (16.3%).", "The primary objective of this study was to investigate structural changes, as measured by joint space narrowing (JSN), within the knee joint during treatment with intra-articular sodium hyaluronate (HA) of molecular weight 500-730 kDa in patients with osteoarthritis (OA) of the knee. Patients received a weekly intra-articular injection of either 20 mg2/ml HA or a 2 ml vehicle placebo (saline) for three weeks. This course was repeated twice more at four-monthly intervals. Concomitant treatment with analgesics or NSAIDs was allowed. The primary efficacy measure was the reduction in mean joint space width (JSW) of the medial compartment at 52 weeks. A total of 408 patients were randomised and 319 completed the one-year study (HA: n=160, placebo: n=159); 273 of the 319 were included in the primary analysis. Analysis of variance on these 273 patients did not show a statistically significant difference between the two treatment groups. However, there was a significant difference in response to treatment in terms of the baseline JSW (p=0.01), indicating that outcome of treatment may depend on-baseline JSW. Therefore, a subgroup analysis by baseline JSW was conducted. This compared patients with a JSW >4.6 mm with those with a JSW <4.6 mm. In those with radiologically milder disease at baseline and receiving HA, the JSN was significantly reduced compared with placebo (p=0.02). In patients with radiologically more severe disease there was no difference in JSN between the two treatments. Although, in this one-year study, no overall treatment effect was seen, those with radiologically milder disease at baseline had less progression of joint space narrowing when treated with HA.", "Thirty-eight patients with symptomatic knee osteoarthritis without mechanical symptoms were randomised after informed consent to receive either a course of intra-articular Hyalgan injections or an arthroscopic washout. The patients were prospectively assessed pre-intervention, 6 weeks, 3 months, 6 months and 1 year using a 10 cm visual analogue pain score, the Knee Society function score and the Lequesne index. There was no significant difference between the two groups at 6 weeks, 3 months, 6 months or 1 year. The use of intra-articular Hyalgan injections in patients with knee osteoarthritis without mechanical symptoms gives results comparable with arthroscopic washout. Hyalgan is an alternative to arthroscopy in this patient group. Further study is needed to confirm these findings and improve patient selection.", "The goal of this study was to determine whether hyaluronic acid (HA) or progressive knee exercises (PE) can improve functional parameters in patients with osteoarthritis (OA) of the knee. In a prospective clinical trial 200 knees (105 patients) with radiographic Kellgren Lawrence grade III OA were randomized and received either three intra-articular injections of hyaluronic acid (Hylan G-F 20) at one-week intervals or PE for 6 weeks. Patients were evaluated by use of the Hospital for Special Surgery (HSS) Knee Score and followed-up for 18 months. Total HSS score for HA and PE patients improved from 62.6 +/- 13.8 to 88.8 +/- 11.1 and from 65.4 +/- 12.3 to 88.3 +/- 9.1, respectively, at the end of the trial (P < 0.01). There were no statistically significant differences between the groups. Twenty-one patients of the HA group were excluded from the study because they had received another form of therapy. All patients in the PE group completed the trial. The patients who dropped out had also significant improvement from 57.0 +/- 12.9 to 76.7 +/- 11.9 (P < 0.01). This prospective randomized trial confirmed that both HA injections and PE result in functional improvement. HA injections also increase the levels of satisfaction of the OA patients." ]

[ "17539899", "18317253", "15216550", "20022836", "18420756", "17100502", "16325899", "12050092", "18261131" ]

[ "Genetic testing for heart disease susceptibility: potential impact on motivation to quit smoking.", "Health behavior changes after genetic risk assessment for Alzheimer disease: The REVEAL Study.", "Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial.", "Efficacy of genotype notification to Japanese smokers on smoking cessation--an intervention study at workplace.", "Psychological and behavioural impact of genetic testing smokers for lung cancer risk: a phase II exploratory trial.", "Can genetic risk information enhance motivation for smoking cessation? An analogue study.", "An intervention study of smoking cessation with feedback on genetic cancer susceptibility in Japan.", "Incorporating genetic susceptibility feedback into a smoking cessation program for African-American smokers with low income.", "The impact of genetic testing for Crohn's disease, risk magnitude and graphical format on motivation to stop smoking: an experimental analogue study." ]

[ "As genetic tests for common gene variants and multifactorial, lifestyle-related conditions become available, it will be increasingly important to determine the psychological and behavioral impact of this emerging class of genetic tests. Our aim was to examine the potential impact of genetic testing for heart disease susceptibility on psychological predictors of smoking cessation. Two hundred and sixty-one smokers were asked to imagine that they had undergone a test for heart disease risk. They were randomly assigned to a genetic test scenario (low- or high-risk result) or an oxidative test scenario (high-risk result). Smokers in the genetic test-high risk group reported greater intention to quit smoking than smokers in the oxidative test-high risk group (p = 0.009); 30% of this was mediated by their holding stronger beliefs that quitting would reduce their heart disease risk (outcome expectations) (p = 0.011). The effect of genetic test-high risk feedback on outcome expectations was greatest amongst smokers with no heart disease family history (p = 0.038). The results suggest that genetic testing for heart disease risk may enhance interventions designed to improve health via increasing smoking cessation rates. Whether the findings hold true in studies that use real rather than hypothetical genetic tests remains to be seen.", "Risk information for Alzheimer disease (AD) may be communicated through susceptibility gene disclosure, even though this is not currently in clinical use. The REVEAL Study is the first randomized clinical trial of risk assessment for AD with apolipoprotein E (APOE) genotype and numerical risk estimate disclosure. We examined whether APOE genotype and numerical risk disclosure to asymptomatic individuals at high risk for AD alters health behaviors. One hundred sixty-two participants were randomized to either intervention (APOE disclosure) or control (no genotype disclosure) groups. Subjects in both groups received numerical lifetime risk estimates of future AD development based on sex and family history of AD. The intervention group received their APOE genotype. Subjects were informed that no proven preventive measures for AD existed and given an information sheet on preventative therapies under investigation. Participants who learned they were epsilon 4 positive were significantly more likely than epsilon 4 negative participants to report AD-specific health behavior change 1 year after disclosure (adjusted odds ratio: 2.73; 95% confidence interval: 1.14, 6.54; P=0.02). Post hoc analyses revealed similar significant associations between numerical lifetime risk estimates and self-report of AD-specific health behavior change. Despite lack of preventive measures for AD, knowledge of APOE genotype, numerical lifetime risk, or both, influences health behavior.", "This trial tests the hypothesis that confirming a clinical diagnosis of familial hypercholesterolemia (FH) by finding a genetic mutation reduces patients' perceptions of control over the disease and adherence to risk-reducing behaviors. Three hundred forty-one families, comprising 341 hypercholesterolemia probands and 128 adult relatives, were randomized to one of two groups: (a) routine clinical diagnosis; (b) routine clinical diagnosis plus genetic testing (mutation searching in probands and direct gene testing in relatives). The main outcome measures were perceptions of control over hypercholesterolemia, adherence to cholesterol-lowering medication, diet, physical activity, and smoking. There was no support for the main hypothesis: finding a mutation had no impact on perceived control or adherence to risk-reducing behavior (all P-values > 0.10). While all groups believed that lowering cholesterol was an effective way of reducing the risk of a heart attack, participants in whom a mutation was found believed less strongly in the efficacy of diet in reducing their cholesterol level (P = 0.02 at 6 months) and showed a trend in believing more strongly in the efficacy of cholesterol-lowering medication (P = 0.06 at 6 months). In conclusion, finding a mutation to confirm a clinical diagnosis of FH in a previously aware population does not reduce perceptions of control or adherence to risk-reducing behaviors. The pattern of findings leads to the new hypothesis that genetic testing does not affect the extent to which people feel they have control over a condition, but does affect their perceptions of how control is most effectively achieved. Further work is needed to determine whether similar results will be obtained in populations with little previous awareness of their risks.\n Copyright 2004 Wiley-Liss, Inc.", "It is well-known that smoking causes many diseases including cancers. Informing smokers of their genotypes associated with the vulnerability to the harms of smoking may be effective measures for smoking cessation. The present study examined the effects of genotype notification of an oncogene (L-myc) genotype to smokers on their behavior to quit smoking.\n Subjects were 562 employees of a bank who answered to be a smoker for a questionnaire used at annual health checkup at workplace from July to December 2002. Those enrolled on August, October, and December were allocated into the genotype notification group (intervention group), and the rest into the controls. Among 286 smokers allocated into the intervention group, 257 participants (89.9%) agreed to genotype testing. One year after the enrollment, a follow-up questionnaire survey was conducted for all smokers including controls.\n Those who stated to have quitted smoking were 22 (8.0%) among the 276 controls and 15 (5.8%) among the 257 genotype notified participants, providing that the odds ratio (OR) of cessation for the intervention was 0.64 (95% confidence interval, 0.32-1.28). No psychological problems associated with genotype notification were observed.\n The present study did not show positive effects of genotype notification on smoking cessation rate. To elevate the cessation rate, methods to explain and notify genotypes should be improved.", "The behavioural and psychological impact of genetic testing for lung cancer susceptibility was examined among smokers (N = 61) who were randomly allocated to a GSTM1 genetic testing group (with GSTM1-missing or GSTM1-present result) or no-test control group. The GSTM1-missing (higher risk) group reported greater motivation to quit smoking, and both genetic testing groups reported lower depression than the control group at one-week follow-up (p < .05 for all). Differences were not significant at two months follow-up. This study indicates the feasibility of much-needed research into the risks and benefits for individuals of emerging lifestyle-related genetic susceptibility tests.", "Protection motivation theory and the extended parallel processing model are used to predict the motivational impact of information regarding a genetic susceptibility to heart disease. One hundred ninety-eight smokers read 1 of 3 vignettes: gene positive, gene negative, or standard smoking risk information. Analyses examined whether the impact of type of risk information was moderated by smokers' self-efficacy (SE) levels. Key outcomes were intention to quit and intention to attend an information session about quitting. There were significant main effects of SE and of receiving gene-positive risk information on intentions to quit. There was a significant Risk x SE interaction on intentions to attend an information session. SE was not associated with intentions to attend the information session for smokers in the gene-positive group. Intentions to attend the session were negatively associated with SE for smokers in the lower risk groups. Implications for using genetic risk information to motivate smoking cessation are discussed.\n Copyright 2006 APA, all rights reserved.", "To evaluate whether feedback of genetic information regarding an L-myc polymorphism, identified as impacting on tobacco-related cancer risk, has an influence on smoking cessation, an intervention study was conducted.\n We recruited smokers from first-visit outpatients at Aichi Cancer Center Hospital. Six hundred and seventeen participated and were allocated into two groups: the biomarker feedback group (BF) and the follow-up smoking status group (FS). The subjects were asked for their smoking status at enrolment and at 3- and 9-month follow-ups. BF subjects were notified about their L-myc genotype.\n The smoking cessation rate at 9-month follow-up was essentially the same for both BF and FS cases, at 18.8% and 17.0%, respectively (P = 0.798). However, a difference in the rate was evident with non-cancer subjects (12.7% and 8.4%, respectively, P = 0.237), especially in females (15.0% and 4.2%, respectively, P = 0.024). The non-cancer subjects informed of their genotype were more likely to quit smoking than the FS patients; particularly in those having a risky genotype, this was significant (odds ratio: 2.87, P = 0.003). Again it was most prominent in females.\n Feedback regarding an L-myc polymorphism did not impact on smoking cessation overall but appeared to benefit smokers without cancer. In addition, gender could affect the response to the feedback.", "Markers of genetic susceptibility to tobacco-related cancers could personalize harms of smoking and motivate cessation. Our objective was to assess whether a multicomponent intervention that included feedback about genetic susceptibility to lung cancer increased risk perceptions and rates of smoking cessation compared with a standard cessation intervention.\n Our design was a two-arm trial with eligible smokers randomized in a 1:2 ratio to Enhanced Usual Care or Biomarker Feedback (BF). Surveys were conducted at baseline, 6, and 12 months later. The setting was an inner city community health clinic. African-American patients who were current smokers (n = 557) were identified by chart abstraction and provider referral. All smokers received a self-help manual and, if appropriate, nicotine patches. Smokers in the BF arm also were offered a blood test for genotyping the GST(3) gene (GSTM1), sent a test result booklet, and called up to four times by a health educator. Prevalent abstinence was assessed by self-report of having smoked no cigarettes in the prior 7 days at the 6- and 12-month follow-ups and sustained abstinence, i.e., not smoking at either follow-up or in-between.\n Smoking cessation was greater for the BF arm than the Enhanced Usual Care arm (19% versus 10%, respectively; P < 0.006) at 6 months but not at 12 months.\n Smokers agreed to genetic feedback as part of a multicomponent cessation program. Although the program increased short-term cessation rates compared with standard intervention, genetic feedback of susceptibility may not benefit smokers with high baseline risk perceptions.", "Genetic tests may motivate risk-reducing behaviour more than other types of tests because they generate higher risk magnitudes and because their results have high personal relevance. To date, trial designs have not allowed the disentangling of the effects of these two factors. This analogue study examines the independent impacts of risk magnitude and provenance, and of risk display type, on motivation to quit smoking. A total of 180 smokers were randomly allocated to one of the 18 Crohn's disease risk vignettes in a 3 (risk provenance: family history. genetic test mutation positive. genetic test mutation negative) x 3 (risk magnitude: 3%, 6%, 50%) x 2 (display: grouped or dispersed icons) design. The 50% group had significantly higher intentions to quit than the 3% group. A significant risk provenance x magnitude interaction showed that participants in 50% or 6% groups were equally motivated, regardless of risk provenance, while participants in the 3% group had higher intentions associated with a mutation negative result than with a result based on family history alone. Grouped icon displays were more motivating than the dispersed icons. Using genetic tests to estimate risks of common complex conditions may not motivate behaviour change beyond the impact of the numerical risk estimates derived from such tests." ]

[ "1500019", "10764420" ]

[ "A randomized trial of adjuvant chemotherapy after radical hysterectomy in stage Ib-IIa cervical cancer patients with pelvic lymph node metastases.", "Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix." ]

[ "Seventy-one patients with Stage Ib-IIa cervical cancer treated by radical hysterectomy and found to have pelvic lymph node metastases were entered on a randomized trial comparing standard pelvic radiotherapy versus three cycles of combination chemotherapy with cisplatin, vinblastine, and bleomycin followed by pelvic radiotherapy. After a median follow-up of 2.5 years, 24 patients have relapsed. In 12 patients, the first evidence of relapse was in the pelvis, in 11 patients the first relapse was evident at a distant site, and in 1 patient the local recurrence and distant metastases were documented simultaneously. No difference in disease-free or overall survival has emerged between the two treatment groups. Relapse was more common in patients with non-squamous tumors (44%) and in those with metastases in several pelvic lymph nodes. We conclude that patients with pelvic lymph node metastases have a rather poor prognosis, but it remains to be determined how they should best be treated after radical surgery.", "To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma.\n Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT.\n Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group.\n The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix." ]

[ "12548322" ]

[ "A randomized controlled trial of outpatient versus inpatient labour induction with vaginal controlled-release prostaglandin-E2: effectiveness and satisfaction." ]

[ "Outpatient management in obstetrics is expanding, but evidence to support outpatient labour induction is needed.\n To compare the effectiveness, acceptability, duration of hospitalization, and safety of outpatient and inpatient induction of labour with intravaginal controlled-release prosta-glandin-E2 (CR-PGE2).\n A prospective, randomized, controlled trial enrolled 300 women at term with parity < or = 5 and singleton pregnancies in cephalic presentation. Each had an unscarred uterus, a normal non-stress test (NST), and a Bishop score of < or = 6. After insertion of the CR-PGE2, and 1 hour of monitoring, those in the outpatient group were discharged home, to return with onset of labour or 12 hours later for an NST. If not already in labour 24 hours later, the women returned for inpatient induction. Vaginal examination was not repeated before 24 hours unless the patient was contracting and required analgesia. Inpatients remained on the antepartum ward but were otherwise treated similarly. The women in both groups reported ratings of satisfaction, pain, and anxiety over the telephone until they were in labour.\n There were 150 women randomized to outpatient and 150 women to inpatient induction of labour. The number of women who were in labour or who delivered by 24 hours in the outpatient group was 115 (0.77, 95% confidence interval [CI] 0.70-0.84) and in the inpatient group was 107 (0.72, 95% CI 0.64-0.79). The median times to labour were 9.8 hours (95% CI, 8.1-11.4) and 11.4 hours (95% CI, 10.1-12.7), and to delivery were 21.4 hours (95% CI, 19.2-23.5) and 20.7 hours (95% CI, 18.4-23.0), for the outpatient and inpatient groups, respectively. In the outpatient group, 56% of women reported high satisfaction during the initial 12 hours of induction compared to 39% in the inpatient group (p < 0.008). Ratings of pain and anxiety during the first 12 hours of induction were similar. In the outpatient group, women were at home for a median of 8 hours (95% CI, 6.7-9.4) before labour and delivery. There were no significant differences in adverse outcomes.\n This study suggests that outpatient induction of labour with intravaginal CR-PGE2 may be a reasonable option for selected low-risk women; however, further study is needed to confirm the safety of this approach." ]

[ "3903579", "8245589", "21170827", "18181335", "3134815", "3303937" ]

[ "Oral ritodrine and preterm premature rupture of membranes.", "[The efficacy of prophylactic antibiotic and tocolytic therapy for premature rupture of the membranes--a prospective randomized study].", "A randomized, double-masked trial of prophylactic indomethacin tocolysis versus placebo in women with premature rupture of membranes.", "Safety and efficacy of oral nifedipine versus terbutaline injection in preterm labor.", "The therapeutic efficacy and cost-effectiveness of aggressive tocolysis for premature labor associated with premature rupture of the membranes.", "A randomized trial of ritodrine tocolysis versus expectant management in patients with premature rupture of membranes at 25 to 30 weeks of gestation." ]

[ "A prospective randomized study was performed to determine whether or not oral ritodrine therapy significantly prolonged the latent period in patients with prematurely ruptured membranes. Compared with a control group of similar patients, those treated had a significantly prolonged mean latent period. In addition, 47.6% of the treatment group versus 14.2% of the control group had a latent period of more than one week.", "A comparative study in patients with premature rupture of the membranes (PROM) from 25 to 34 weeks of gestation was carried out, prospectively. Group 1 (34 patients) was given aggressively intrauterine therapy including the administration of tocolytic agents (ritodrine and/or magnesium sulfate) and prophylactic antibiotics (AB-PC 2g/day). Group 2 (41 patients) was managed conservatively with bed rest only. At the time of admission to the study, there were no clinical signs of infection, fetal distress, or active labor in either group. All patients were delivered if the pregnancy had reached 35 weeks of gestation or later, had established labor, or developed evidence of chorioamnionitis or fetal distress. Prolongation for more than 72 hours was greater in group 1 than in group 2. There was no difference in the incidence of chorioamnionitis, postpartum endometritis, or placental infection in the groups. However, the incidence of a low Apgar score (7 < at 5 min), requiring artificial ventilation, and infection was more common in group 1. It is concluded that the use of antibiotics and tocolytics might make the management of PROM more complicated.", "Preterm premature rupture of membranes (PPROM) complicates 3% of pregnancies and frequently results in preterm birth, often within 48 hours of membrane rupture. Our objective was to determine if subjects with PPROM between 24 and 31 (6)/ (7) weeks' gestation benefit from a 48-hour course of prophylactic indomethacin tocolysis. This was a double-masked randomized controlled trial. Subjects with PPROM between 24 and 31 (6)/ (7) weeks' gestation were randomized to receive indomethacin or placebo for 48 hours in addition to corticosteroids and latency antibiotics. The primary outcome of the study was delivery within 48 hours. Maternal and neonatal outcomes were also compared. This study was concluded prematurely due to slow accrual after a total of 50 subjects were enrolled. A total of 23/25 (92%) subjects in the indomethacin group remained pregnant beyond 48 hours compared with 20/22 (90.9%) in the placebo group (relative risk, 1.01; 95% confidence interval, 0.84 to 1.21). The latency period medians and interquartile ranges were similar between the two groups [indomethacin 193 (92 to 376.5) hours versus placebo 199 (77.5 to 459) hours, P = 0.91], and no differences were noted in any maternal or neonatal secondary outcomes. This limited study demonstrates no benefit with the use of prophylactic indomethacin tocolysis for women with PPROM.\n © Thieme Medical Publishers.", "To compare the safety and tocolytic efficacy of oral nifedipine with intravenous terbutaline for the management of threatened preterm labor.\n Pregnant women between 24 and 36 completed weeks of single gestation with preterm labor were randomized to either oral nifedipine (n=20) or intravenous terbutaline (n=20) treatment. Nifedipine (immediate released capsule) 10 mg was crushed and swallowed, 10 mg every 20 minutes was allowed if necessary with a maximum 40 mg in the first hour. After that 20 mg nifedipine every 4 hours was given, up to 72 hours. Terbutaline was initially infused with the rate 10 g/min with an increment 5 microg/min every 10 minutes if required, until 25 microg/min was reached. Once the contractions had stopped for 2-6 hours, the patients were switched to subcutaneous injection with 0.25 mg terbutaline every 4 hours for 24 hours. The main safety outcome was the changes in maternal diastolic blood pressure from baseline and 1 hour after starting the treatment (deltaDBP(1hr)). Secondary outcomes were the efficacy to delay delivery > or =48 hours and 7 days, the adverse events and the birth outcomes.\n deltaDBP(1hr) was greater in the terbutaline group than that in the nifedipine group with no statistically significant difference. Hypotension (defined as BP < or = 90/60 mmHg) was found in one patient of the nifedipine group and two patients of the terbutaline group. Seventeen and 14 patients in the nifedipine group and 15 and 12 patients in the terbutaline group had delayed delivery > or =48 hours and 7 days, respectively. Mothers in the nifedipine group experienced fewer side effects than those in the terbutaline group. Maternal heart rate, at I hour after starting the treatment, increased significantly higher in the terbutaline group than in the nifedipine group. Birth outcomes were measured in all nifedipine group patients, but in only 16 of the terbutaline group patients. Six mothers in each group delivered after 37 weeks. Intraventricular hemorrhage (IVH) occurred in three babies (gestational aged 25, 29 and 37 weeks) born to mothers treated with terbutaline. In one baby, IVH related to trauma resulted from the delivery procedure.\n The safety and efficacy of nifedipine compares with that of terbutaline for treatment of preterm labor.", "We conducted a randomized trial comparing bed rest with tocolysis to determine the therapeutic efficacy, safety, and cost-effectiveness of tocolysis for the treatment of preterm labor after membrane rupture. One hundred nine women participated over a 26-month interval. Treatment groups did not differ significantly in terms of gestational age at membrane rupture, gestational age at delivery, birth weight, maternal or fetal infectious morbidity, respiratory distress syndrome, necrotizing enterocolitis, or perinatal mortality. Prolongation of intrauterine time after the onset of uterine contractions was seen in women receiving tocolysis (105.2 +/- 157 hours versus 62.1 +/- 77 hours, p = 0.06). This prolongation was not associated with a significant reduction in the total cost per surviving infant (tocolysis, $38,593 +/- $40,887 versus bed rest, $43,158 +/- $37,116; p = 0.445). The cost difference was artifactual. The number of very premature infants born (less than 28 weeks' gestation) was unequal in the two groups (12 in the bed rest group and 5 in the tocolysis group) and skewed the results. Before 28 weeks' gestation tocolysis was associated with a significant increase in intrauterine time after the onset of regular contractions (p = 0.05). However, there was no identifiable perinatal benefit garnered from the additional 5 days. After 28 weeks there were no significant differences between treatment groups in terms of intrauterine time after the onset of regular contractions and total cost per surviving infant. Because tocolysis does not improve perinatal outcome and can itself be associated with major maternal morbidity, it should be avoided after 28 weeks' gestation. Before 28 weeks' gestation tocolysis may greatly increase intrauterine time, but the benefit of this prolongation is not clear.", "Expectant management was compared with similar management plus ritodrine tocolysis in a randomized controlled trial in patients with premature rupture of membranes at 25 to 30 weeks of gestation. In the tocolysis group intravenously administered ritodrine was instituted at the onset of labor and then changed to the oral form if successful. Tocolysis was discontinued or not instituted after 31 weeks of gestation. Seventy-nine patients were randomized over a 4-year period, 39 in the tocolysis group and 40 in the expectant group. Twenty-three patients in the tocolysis group actually received ritodrine. No difference between the two groups was demonstrated in the interval between premature rupture of membranes and delivery or in reaching 32 weeks of gestation. No statistical difference was seen in maternal morbidity. Birth weights and gestational ages at delivery were similar between the two groups as were the incidences of neonatal morbidities caused by prematurity and infection and in the duration of neonatal hospital stays. Despite being conducted in those gestational ages in which prolongation of pregnancy might be expected to be of most benefit, no difference could be demonstrated with the addition of tocolytic therapy over expectant management alone." ]

[ "19137351", "8093267", "12851191", "17652295", "12697798", "14997286", "12521969", "12810740", "11087879", "15374046", "11605747", "15381506", "11315240", "9284784" ]

[ "External hip protectors are effective for the elderly with higher-than-average risk factors for hip fractures.", "Effect of external hip protectors on hip fractures.", "Randomised controlled trial of hip protectors for the prevention of second hip fractures.", "Efficacy of a hip protector to prevent hip fracture in nursing home residents: the HIP PRO randomized controlled trial.", "Prevention of hip fractures by external hip protectors: a randomized controlled trial.", "Randomized controlled trial of hip protectors among women living in the community.", "Effect on hip fractures of increased use of hip protectors in nursing homes: cluster randomised controlled trial.", "A randomised trial of hip protector use by frail older women living in their own homes.", "Prevention of hip fracture in elderly people with use of a hip protector.", "Effectiveness and acceptability of a newly designed hip protector: a pilot study.", "Acceptance of hip protectors for hip fracture prevention in nursing homes.", "A cluster randomised controlled trial to evaluate a policy of making hip protectors available to residents of nursing homes.", "Hip fracture prevention trial using hip protectors in Japanese nursing homes.", "External hip protectors to prevent osteoporotic hip fractures." ]

[ "In our cluster randomised controlled trial for efficacy of hip protector with 672 ambulatory elderly women, a hip protector was more effective for prevention of hip fractures in residents with fall history (n = 202; hazard ratio (HR), 0.375; 95%CI, 0.14-0.98; p = 0.05) and body-mass index (BMI) < or = 19.0 (n = 206; HR, 0.37; 95%CI, 0.14-0.95; p = 0.04) by a Cox proportional hazards regression model.\n Hip fractures result from both osteoporosis and falling. A potentially cost-effective method of preventing hip fractures involves the use of hip protectors but recent studies have revealed the uncertain effectiveness of hip protectors even in institutional settings.\n This study was a cluster randomised controlled trial with nursing homes. We randomly assigned 76 homes with 672 ambulatory but frail elderly women. Several risk factors were assessed at baseline and incorporated into a Cox proportional hazards regression model. UMIN Clinical Trials Registry number is UMIN000000467. Research period was between January 2004 and March 2006.\n In the intervention group, 19 hip fractures occurred (54.0/1,000 person-years), whereas 39 hip fractures occurred in the control group (78.8/1,000 person-years). Hazard ratio of hip fracture in the intervention group was 0.56 (95%CI, 0.31-1.03; p = 0.06) after adjusting for risk factors. In subgroup analysis, hip protectors were more effective for prevention of hip fractures in residents with fall history (n = 202; HR, 0.375; 95%CI, 0.14-0.98; p = 0.05) and BMI < or = 19.0 (n = 206; HR, 0.37; 95%CI, 0.14-0.95; p = 0.04). Overall compliance with use of hip protectors was 79.7%.\n Risk of hip fracture can be reduced by hip protectors among elderly women with fall history and low BMI.", "Most hip fractures seem to be related to trauma near the hip, so a controlled trial was conducted to investigate the effect of external hip protectors on the prevention of such fractures in residents of a nursing home. 10 of the 28 wards in the nursing home were randomised to receive external hip protectors; thus 167 women and 80 men were given protectors and 277 and 141 men no protectors. A fall register was set up for 2 treatment wards (45 residents) and 2 control wards (76 residents). There were 8 hip and 15 non-hip fractures in the hip-protector group and 31 hip and 27 non-hip fractures in the control group. The relative risk of hip fractures among women and men in the intervention group was 0.44 (95% CI 0.21-0.94). None of the 8 residents in the intervention group who had a hip fracture was wearing the device at the time of the fracture. 154 falls were registered and 20% of these falls produced a direct impact to the hip. In 25 falls direct impact to the hip was sustained at a time when hip protectors were not being worn, and 6 fractures were produced. The study indicates that external hip protectors can prevent hip fractures in nursing-home residents.", "to assess whether the use of Safehip hip protectors would prevent second hip fractures among men and women living in the community.\n pragmatic randomised controlled trial.\n people living in the community.\n men and women aged 70 years and over who had sustained one hip fracture and who were living in the community.\n 366 men and women who were either living outside residential care or were about to be discharged back home were randomised to receive three pairs of hip protectors or to act as controls. Approximately 34% of participants allocated to receive hip protectors wore them every day. After a median follow up of 14 months 8 participants had a second hip fracture with 6 in the intervention and 2 in the control group (Odds Ratio for second hip fracture=3.10, 95% confidence interval 0.62-15.58). Hip protectors had no effect on risk of other fractures or on falls.\n this trial does not suggest a benefit of the studied hip protector among people living outside residential accommodation.", "Past studies of the efficacy of hip protectors to prevent hip fracture in nursing home residents have had conflicting results, possibly due to potential biases from clustered randomization designs and modest adherence to intervention.\n To determine whether an energy-absorbing and energy-dispersing hip protector would reduce the risk of hip fracture when worn by nursing home residents.\n Multicenter, randomized controlled clinical trial in which 37 nursing homes were randomly assigned to having residents wear a 1-sided hip protector on the left or right hip. Participants were 1042 nursing home residents (mean [SD] aged 85 [7] years; 79% women) who consented and adhered to the hip protector use during a 2-week run-in period and were enrolled. Participating facilities were in greater Boston, Massachusetts, St Louis, Missouri, and Baltimore, Maryland from October 2002 to October 2004. Mean duration of participation for nursing home residents was 7.8 months. None were withdrawn because of adverse effects.\n Undergarments with a 1-sided hip protector made of a 0.32-cm outer layer of polyethylene (2.7 kg/m3) backed by a hard high-density polyethylene shield (0.95 cm) that was backed by 0.9 kg/m3 of 1.27-kg ethylene vinyl acetate foam. Each facility was visited 3 times per week to assess adherence and provide staff support.\n Adjudicated hip fracture occurrences on padded vs unpadded hips.\n After a 20-month follow-up (676 person-years of observation), the study was terminated due to a lack of efficacy. The incidence rate of hip fracture on protected vs unprotected hips did not differ (3.1%; 95% confidence interval [CI], 1.8%-4.4% vs 2.5%; 95% CI, 1.3%-3.7%; P = .70). For the 334 nursing home residents with greater than 80% adherence to hip protector use, the incidence rate of hip fracture on protected vs unprotected hips did not differ (5.3%; 95% CI, 2.6%-8.8% vs 3.5%; 95% CI, 1.3%-5.7%; P = .42). Overall adherence was 73.8%.\n In this clinical trial of an energy-absorbing/shunting hip protector conducted in US nursing homes, we were unable to detect a protective effect on the risk of hip fracture, despite good adherence to protocol. These results add to the increasing body of evidence that hip protectors, as currently designed, are not effective for preventing hip fracture among nursing home residents.\n clinicaltrials.gov Identifier: NCT00058864.", "Several randomized controlled trials have been performed to examine the effectiveness of external hip protectors in reducing the incidence of hip fractures, but the results are controversial.\n To examine the effectiveness of hip protectors in reducing the incidence of hip fractures in an elderly high-risk population.\n Randomized controlled trial of elderly persons aged 70 years or older, who have low bone density, and are at high risk for falls. Participants lived in apartment houses for the elderly, homes for the elderly, and nursing homes in Amsterdam and surrounding areas in the Netherlands. They were enrolled in the study between March 1999 and March 2001; the mean follow-up was 69.6 weeks. Of the 830 persons who were screened, 561 persons were enrolled.\n External hip protector. Both groups received written information on bone health and risk factors for falls.\n Time to first hip fracture. Survival analysis was used to include all participants for the time they participated.\n In the intervention group, 18 hip fractures occurred vs 20 in the control group. Four hip fractures in the intervention group occurred while an individual was wearing a hip protector. At least 4 hip fractures in the intervention group occurred late at night or early in the morning. Both in univariate analysis (log-rank P =.86) and in multivariate analysis (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.55-2.03), no statistically significant difference between the intervention group and control group was found with regard to time to first hip fracture. In addition, the per protocol analysis in compliant participants did not show a statistically significant difference between the groups (HR, 0.77; 95% CI, 0.25-2.38).\n The hip protector studied was not effective in preventing hip fractures.", "To assess whether hip protectors used among women living in the community in the United Kingdom and at high risk of hip fracture, lead to a reduction in hip fracture.\n Pragmatic randomized controlled trial (RCT).\n Primary care with participants being recruited largely from general practitioners' patient lists.\n Women aged 70 years and over with one or more risk factors for hip fracture (i.e., low body weight, current smoker, a prior fracture, family history of hip fracture).\n Three pairs of hip protectors of the \"shell\" type mailed to participants with instructions on how to use them.\n Reduction in hip fractures.\n 1,388 and 2,781 women aged 70 years or over were randomized to be given three pairs of hip protectors or act as controls, respectively. We followed up both groups of women for a minimum of 24 months (maximum 42 months, median 28). Compliance was poor with only 31% of participants reporting that they wore the hip protectors on a daily basis at 12 months. Intention-to-treat analysis showed that there was no statistically significant difference in the unadjusted odds ratios (ORs) of sustaining a hip fracture between the groups (OR = 1.19; 95% confidence interval, 0.80 to 1.78, p = 0.40). Adjustment for important covariates did not materially change these findings (OR = 1.17; 95% CI, 0.78 to 1.75). Comparing the rate of hip fracture between those women who regularly wore the devices and the control group yielded an OR of 1.12 (95% CI, 0.58 to 2.03; p = 0.83).\n This study is the largest RCT of hip protectors to date and provides no evidence of an effect of hip protectors among women living independently and at high risk of fracture.", "To assess the effects of an intervention programme designed to increase use of hip protectors in elderly people in nursing homes.\n Cluster randomised controlled trial with 18 months of follow up.\n Nursing homes in Hamburg (25 clusters in intervention group; 24 in control group). Participants: Residents with a high risk of falling (459 in intervention group; 483 in control group). Intervention: Single education session for nursing staff, who then educated residents; provision of three hip protectors per resident in intervention group. Usual care optimised by brief information to nursing staff about hip protectors and provision of two hip protectors per cluster for demonstration purposes.\n Incidence of hip fractures.\n Mean follow up was 15 months for the intervention group and 14 months for the control group. In total 167 residents in the intervention group and 207 in the control group died or moved away. There were 21 hip fractures in 21 (4.6%) residents in the intervention group and 42 hip fractures in 39 (8.1%) residents in the control group (relative risk 0.57, absolute risk difference -3.5%, 95% confidence interval -7.3% to 0.3%, P=0.072). After adjustment for the cluster randomisation the proportions of fallers who used a hip protector were 68% and 15% respectively (mean difference 53%, 38% to 67%, P=0.0001). There were 39 other fractures in the intervention group and 38 in the control group.\n The introduction of a structured education programme and the provision of free hip protectors in nursing homes increases the use of protectors and may reduce the number of hip fractures.", "To investigate the efficacy and effectiveness of hip protectors in frail community living older women.\n Randomised controlled trial.\n Aged care health services in New South Wales, Australia.\n 600 women 74 years of age or more (mean age 83 years), who had two or more falls or one fall requiring hospital admission in the previous year, and who lived in their own homes.\n Use of hip protectors.\n Adherence with use of hip protectors, falls, incidence of hip fracture, and adverse effects of use of hip protectors.\n Adherence was approximately 53% over the duration of the study and hip protectors were worn at the time of 51% of falls in the intervention group. The risk of hip fracture when falling while wearing hip protectors, compared with a fall with no hip protectors in place, was significantly reduced (relative risk (RR) 0.23, 95% confidence interval (CI) 0.08 to 0.67). On an intention to treat analysis, 21 and 22 hip fractures occurred in the intervention and control groups respectively (adjusted RR 0.92, 95% CI 0.51 to 1.68). Three users of hip protectors sustained a hip fracture while wearing properly applied protectors, while 16 hip protector users (5%) developed minor local complications.\n Hip protectors prevent hip fractures in community dwelling older women if worn at the time of a fall. The overall effectiveness of hip protectors was not established in this study, because of incomplete adherence with use of the protectors, and limited statistical power.", "Hip fractures are common in frail elderly adults worldwide. We investigated the effect of an anatomically designed external hip protector on the risk of these age-related fractures.\n We randomly assigned 1801 ambulatory but frail elderly adults (1409 women and 392 men; mean age, 82 years), in a 1:2 ratio, either to a group that wore a hip protector or to a control group. Fractures of the hip and all other fractures were recorded until the end of the first full month after 62 hip fractures had occurred in the control group. The risk of fracture in the two groups was compared, and in the hip-protector group the risk of fracture was also analyzed according to whether the protector had been in use at the time of a fall.\n During follow-up, 13 subjects in the hip-protector group had a hip fracture, as compared with 67 subjects in the control group. The respective rates of hip fracture were 21.3 and 46.0 per 1000 person-years (relative hazard in the hip-protector group, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.008). The risk of pelvic fracture was slightly but not significantly lower in the hip-protector group than in the control group (2 subjects and 12 subjects, respectively, had pelvic fracture) (relative hazard, 0.4; 95 percent confidence interval, 0.1 to 1.8; P > or = 0.05). The risk of other fractures was similar in the two groups. In the hip-protector group, four subjects had a hip fracture (among 1034 falls) while wearing the protector, and nine subjects had a hip fracture (among 370 falls) while not wearing the protector (relative hazard, 0.2; 95 percent confidence interval, 0.05 to 0.5; P=0.002).\n The risk of hip fracture can be reduced in frail elderly adults by the use of an anatomically designed external hip protector.", "Hip fracture has a significant economic and personal cost, involving hospital admission and functional impairment for elderly people. To assess the benefit of using a newly designed hip protector (new material and new design) to prevent fracture in a realistic setting, a randomised intervention-control design was used to trial the effectiveness of pads worn by high falls risk residents (n=71) in nursing home for 9 months. 40 residents were in the intervention group and 31 were in the control group. A profile of falls, including time of day, and orientation was obtained to demonstrate the potential effectiveness of the protectors for injury prevention. Acceptance of the hip protector was also surveyed amongst nursing home staff and residents. One hundred and one falls and six fractures occurred in the control group. In contrast, one hundred and ninety one falls and three fractures occurred in the hip protector (pads) group. The three fractures in the protector wearing group occurred when pads were not in place. This was extrapolated as 1 in every 16.8 falls and 1 in every 63.7 falls resulting in fracture in the two groups, respectively. The relative risk of fracture was 0.264 (95% CI=0.073-0.959) when the fracture incidence rate in the intervention group (three fractures per 191 falls) was compared to the control group (six fractures per 101 falls). This is a statistically significant result and implies that this newly designed hip protector is effective in preventing hip fracture. The majority of falls occurred during the day, which was when protectors were worn in this study, but the data on orientation was incomplete, with direction unknown in 74% of falls. Compliance was an issue, which was interpreted as only 50.3% of falls recorded with protectors in place. Dementia was identified as the explanation for this as the pads were often removed by these residents who comprised the majority of participants. Perception of low risk was the primary barrier to residents accepting the intervention. Comfort of protectors was not a significant concern for staff or residents, and only staff described appearance as an issue. In conclusion, the newly designed hip protector is protective against fractures in a realistic setting. Compliance and acceptance of the protectors will ultimately determine the viability of this prophylaxis.", "In order to prevent hip fractures 548 fall-prone senior citizens living in 20 nursing homes participated in a randomized controlled trial of hip protectors. One hundred and sixty-four were randomly selected into the control group and 384 into the intervention group. Of the patients in the intervention group 138 (35.9%) wore the protector throughout the whole 10 months of the study's duration, 124 (32.3%) quit wearing the protectors after an initial wearing period and 122 (31.8%) refused to wear them at all. The regular wearers had the protector on during an average of roughly 12 hours a day, so they were protected for 50% of their exposure time (including at night). Fifty-nine percent of the drop-outs stopped wearing the protectors in the first two study months, mostly for non-medical reasons. Calculation by a forecasting model showed that those senior citizens who were initially prepared to wear the protector tended to be those who were physically restricted.", "to evaluate the effectiveness of a policy of making hip protectors available to residents of nursing homes.\n a cluster randomised controlled trial of the policy in nursing and residential homes, with the home as the unit of randomisation.\n 127 nursing and residential homes in the greater Belfast area of Northern Ireland.\n 40 homes in the intervention group (representing 1,366 occupied beds) and 87 homes in the control group (representing 2,751 occupied beds).\n a policy of making hip protectors available free of charge to residents of nursing homes and supporting the implementation process by employing a nurse facilitator to encourage staff in the homes to promote their use, over a 72-week period.\n the rate of hip fractures in intervention and control homes, and the level of adherence to use of hip protectors.\n there were 85 hip fractures in the intervention homes and 163 in the control homes. The mean fracture rate per 100 residents was 6.22 in the intervention homes and 5.92 in the control homes, giving an adjusted rate ratio for the intervention group compared to the control group of 1.05 (95% CI 0.77, 1.43, P = 0.76). Initial acceptance of the hip protectors was 37.2% (508/1,366) with adherence falling to 19.9% (272/1,366) at 72 weeks.\n making hip protectors available to residents of nursing and residential homes did not reduce the rate of hip fracture. This research does not support the introduction of a policy of providing hip protectors to residents of nursing homes.", "A method to protect the hips during falls could effectively reduce the incidence of hip fractures. We report the results of the first hip protector trial in Japan, performed between July 1996, and September 1999. One hundred and sixty-four elderly female residents of nursing homes, with Activities of Daily Living above the wheelchair level, agreed to participate in this study. Among them, 88 were randomly selected to wear a hip protector and 76 controls did not. All falls and resulting injuries were recorded daily. In anthropometric measurements and ultrasonic bone evaluation, no significant differences were found between the two groups, except in height. During an average of 377 days, the wearers and the non-wearers fell a total of 131 and 90 times, respectively. Among the wearers, there were two non-hip fractures and one hip fracture, so the annual hip fracture rate was calculated at 1.2%, against 8 hip fractures among the non-wearers, or 9.7% per year. The hip fracture rate was significantly lower among the wearers than non-wearers, while the annual number of falls per subject and the distribution of fallers remained the same. According to Cox's proportional hazard regression analysis, the effect of the hip protector on hip fracture prevention was independent of anthropometric data, ultrasonic bone assessment values or number of falls. Moreover, even after limiting the subjects to fallers only, the annual hip fracture rate in non-wearers was higher than in wearers (19.8% vs 2.0%) and the annual hip fracture rate per fall in wearers was lower than that in non-wearers (0.8% vs 8.2%). It was thus concluded that the hip protector is a beneficial device for the prevention of hip fractures.", "nan" ]

[ "1941727", "1478135" ]

[ "Out of the darkness: group cognitive therapy for depressed elderly.", "[Active music therapy for senile depression]." ]

[ "1. Depression affects an estimated 50% of the population over age 65. With the current expansion of the elderly in this country, the problem will continue to increase. 2. Depressed individuals view situations negatively when more positive interpretations are equally valid. The thrust of cognitive therapy is to replace the faulty and negative perceptions with more valid and positive ones. 3. Cognitive therapy was found to be effective in the elderly. Residents attended sessions regularly, and the change in the depression level for group participants was highly significant statistically and clinically noticeable.", "68 cases with senile depression were divided randomly into two groups--test group and control group. Patients of both groups received same antidepressive drugs while for the patients in the test group active music therapy was provided everyday in addition and the course of music therapy was 8 weeks. Patients in the test group showed improvement of their symptoms at the end of first week while most patients in the control group were getting somewhat better at the 3rd-4th week. The effectiveness of combined treatment in the test group is better than that in the control group. Patients in the test group became calm and active and the atmosphere on the ward appeared to be somewhat harmonized so that it was beneficial to the nursing care." ]

[ "3510820", "3046537", "2778469", "2365041", "6340975", "1092531", "7013150", "3896217", "2038732", "4003919", "1099948", "1984814" ]

[ "Efficacy of inhaled metaproterenol and orally-administered theophylline in patients with chronic airflow obstruction.", "Acute response to bronchodilator. An imperfect guide for bronchodilator therapy in chronic airflow limitation.", "Should study subjects see their previous responses: data from a randomized control trial.", "Domiciliary nebulized terbutaline in severe chronic airways obstruction.", "Breathlessness and exercise tolerance in chronic airflow obstruction: 2-hourly versus 4-hourly salbutamol by inhalation.", "Response of patients with chronic obstructive lung disease to the regular administration of nebulized isoproterenol. A double-blind crossover study.", "Domiciliary nebulised salbutamol solution in severe chronic airway obstruction.", "Evaluation of domiciliary treatment with terbutaline by wet nebulisation in patients with chronic bronchitis and emphysema.", "Bronchodilator treatment for partially reversible chronic obstructive airways disease.", "The efficacy of orally administered theophylline, inhaled salbutamol, and a combination of the two as chronic therapy in the management of chronic bronchitis with reversible air-flow obstruction.", "A comparative study of atropine sulfate and isoproterenol hydrochloride in chronic bronchitis.", "Mechanism of bronchodilator effect in chronic airflow limitation." ]

[ "To evaluate comparative bronchodilator efficacy with chronic airflow obstruction (CAO), we randomly administered to ten patients week-long treatments consisting of: inhaled metaproterenol from a metered dose canister (1.30 mg six times a day) and doses of a sustained-release theophylline formulation sufficient to achieve plasma levels of 10-15 micrograms/ml; metaproterenol-placebo; theophylline-placebo; or placebo-placebo. At the end of each period, treatment responses were evaluated by spirometric tests, by exercise tolerance (12 minute walk and progressive cycle ergometry) and by subjective perception of dyspnea (oxygen cost diagram and breathlessness rating). Metaproterenol as a single treatment caused statistically significant improvements in spirometric variables and in the breathlessness rating. Theophylline as a single treatment caused significant changes in none of the test variables, though favorable trends were observed. Combined drug therapy was significantly better than metaproterenol only in the case of the breathlessness rating. We conclude that in the treatment of patients with CAO, inhaled metaproterenol is superior to oral theophylline. Our results permit no definite conclusion concerning added benefits of combined drug therapy.", "We conducted a four-period cross-over randomized trial in which we found that patients with chronic airflow limitation demonstrated symptomatic improvement with both inhaled albuterol and oral theophylline. The response, however, was not uniform. We therefore tested the ability of acute change in forced expired volume in one second (FEV1) following inhaled beta agonist to predict long-term symptomatic response to albuterol and theophylline. We found that the reproducibility of acute change in FEV1 over three repetitions was poor (intraclass correlation 0.17). Furthermore, the mean improvement FEV1 following inhaled albuterol across the three repetitions did not relate closely to symptomatic response to either albuterol or theophylline. We conclude that acute response to inhaled beta agonist is not useful for identifying patients with chronic airflow limitation who are likely to benefit from bronchodilator treatment.", "To test the relative merits of administering questionnaires with previous responses available (the informed condition) or unavailable (the blind condition), we administered blind and informed versions of a quality of life questionnaire (the Chronic Respiratory Disease Questionnaire, or CRQ) in a randomized, double-blind trial of bronchodilators in chronic airflow limitation. The responsiveness of the two methods, as reflected in the p-values associated with salbutamol and theophylline effects were comparable for three of the four dimensions of the CRQ. The data suggested possible increased responsiveness of the informed method for the emotional function dimension of the questionnaire. Changes in the informed CRQ dyspnea and fatigue dimensions showed stronger correlations with changes in spirometry, 6 minute walk distance, and rating of dyspnea after the walk test than did blind administration. Further, changes in all four CRQ dimensions showed stronger correlations with corresponding global ratings using the informed questionnaire. These results suggest that by letting study subjects see their previous responses the validity of subjective measures of health status in clinical trials can be improved.", "Forty-eight patients with severe chronic airways obstruction were given 5 mg terbutaline or placebo from a nebulizer twice daily for 2 + 2 weeks. Twenty three patients preferred terbutaline, 9 placebo and 16 had no preference. The baseline lung function and the 6 minute walking distance were not increased after the terbutaline period. The patients who preferred terbutaline indicated less dyspnoea after the terbutaline period as compared to the placebo period, but did not differ with regard to lung function or walking distance after the terbutaline treatment. The physiology behind the subjective relief from the terbutaline inhalations remains unexplained.", "Breathlessness, exercise tolerance, and spirometry were measured in 12 patients whose major symptom was breathlessness, secondary to severe chronic airflow limitation, during a double-blind crossover comparison of inhaled salbutamol in two dosages (200 micrograms 4-hourly and 200 micrograms 2-hourly) with placebo. Daily visual analogue scores of breathlessness, exercise tolerance and spirometry were all significantly improved with salbutamol in both dosages compared to placebo. The 2-hourly regimen was superior to the 4-hourly regimen only in terms of exercise tolerance. Walking distance had deteriorated significantly 2 hours after salbutamol on the 4-hourly regimen and was usefully increased by an extra dose of salbutamol on the 2-hourly regimen at the equivalent time, without side-effects. Salbutamol provided considerable symptomatic relief in addition to spirometric improvement in patients with chronic airflow limitation.", "The effect of the regular use of neublized isoproterenol in 14 patients with symptomatic chronic obstructive lung disease (COLD) was evaluated in a double-blind crossover 16-week study. FEV1, FVC and SGaw were measured before and 45 minutes after bronchodilator therapy every two weeks, while arterial blood gases were measured every eight weeks, before and 45 minutes after bronchodilator therapy. When the patients were considered as a group, there was no significant difference in mean symptom scores or objective pulmonary functions during the drug and placebo periods. Four patients had significantly higher (p less than .05) and two patients significantly lower mean values for at least one of the pulmonary function tests during the isoproterenol period. The patient who is most likely to benefit from isoproterenol on a regular basis appears to have the following characteristics; (1) consistent improvement in pulmonary function tests 45 minutes after use of nebulized bronchodilator; (2) moderate rather than severe COLD; and (3) a relatively normal DLCO.", "Nine patients with severe chronic airway obstruction secondary to chronic bronchitis and emphysema all preferred nebulised salbutamol solution to placebo in a double-blind controlled trial. Four of the patients who had previously received domiciliary nebulised salbutamol failed to complete the placebo period, though all completed the active period. Five others improved subjectively on active therapy, and showed a significant improvement in morning and evening peak flows. Symptom scores for breathlessness, wheezing, and sputum production were lower in the active treatment period and standard aerosol usage fell, although these changes might have been due to chance. Patients with severe chronic airway obstruction who do not respond to conventional bronchodilator therapy should be considered for this form of treatment.", "Domiciliary treatment with terbutaline by wet nebulisation (5 mg, four times daily) was compared with placebo in a double-blind study over four consecutive periods, each of seven days duration, in eight patients with severe airflow limitation due to chronic bronchitis and emphysema. Lung function tests performed at the conclusion of each treatment period showed small but significant improvements in FEV1 before and after 500 micrograms of terbutaline by metered dose inhaler (MDI), with reductions in functional residual capacity and residual volume for terbutaline compared with placebo. Morning and evening peak expiratory flow rate recordings were greater and there was a significant reduction in the use of terbutaline by MDI during the terbutaline treatment. Three patients were unable to complete the placebo treatment because of excessive symptoms. Analysing all individual results, only one patient appeared not to benefit from nebulised terbutaline, while the preference rating for the other seven patients was significantly in favour of terbutaline.", "The effect of six weeks' treatment with inhaled terbutaline (1 mg four times a day), optimised doses of theophylline (twice a day), the combination of theophylline and terbutaline, and placebo was studied in a randomised, double blind, crossover trial. Thirty patients with partially reversible chronic airflow obstruction and a mean forced expiratory volume in one second (FEV1) of 1.2 litres that improved by 25% were included in the study. Patients who developed non-infective exacerbations of airflow obstruction that required additional bronchodilator treatment were classed as \"treatment failures.\" Such treatment failure occurred in 23 patients with placebo, in 22 patients with theophylline, in 12 patients with terbutaline, and in two patients taking the two drugs. Mean daily peak flow readings were highest with the combination of the two drugs, followed by terbutaline and then theophylline, and lowest with placebo. Thus a combination of terbutaline and theophylline was superior to either drug alone; inhaled terbutaline was superior to theophylline alone. Theophylline alone does not appear to have much place in the management of patients with partially reversible obstructive airways disease.", "The efficacy of bronchodilator therapy was assessed in the long-term management of patients with chronic bronchitis and varying degrees of reversible air-flow obstruction. Twenty-five patients with a mean forced expiratory volume in one second (FEV1) 38.7% predicted received: optimized doses of orally administered, sustained-release theophylline, inhaled salbutamol (200 micrograms 4 times a day), a combination of the 2 drugs, and identical placebo therapy for periods of 3 wk in a randomized, double-blind, crossover trial. Patients who deteriorated during treatment were assessed immediately and designated \"treatment failures\" if additional therapy proved necessary. Such \"failures\" occurred in 9 patients with placebo, in 8 with salbutamol, in 6 with theophylline, and in only 1 with combined therapy. Using a ranking system based on \"treatment failures\" and mean daily peak flow rates, first preference was given to combined therapy in 13 patients, theophylline in 6, salbutamol in 4, and placebo in 2. Thus, both combined therapy (p less than 0.001) and theophylline (p less than 0.05) were better than placebo, but this was not so for inhaled salbutamol. Objective improvements in FEV1 and forced vital capacity were a consistent finding with combined therapy compared with placebo, although not with single agents, and additive effects were clearly demonstrated. In the subgroup of patients able to tolerate placebo therapy, no subjective benefit could be discerned during any of the 3 periods of active treatment. Thus, the combination of orally administered, sustained-release theophylline and inhaled salbutamol offered significant advantages in the clinical control of patients with chronic bronchitis with air-flow obstruction.", "Fifteen subjects with chronic bronchitis were treated with inhaled atropine sulfate, isoproterenol hydrochloride, or placebo in a double blind crossover trial. Each drug was inhaled 4 times per day for 3 weeks. Baseline forced expiratory flows, specific airway conductance, airway resistnace, and functional residual capacity were measured weekly. These measurements were repeated 15 min and 60 min after laboratory inhalation of each agent, using a separate double blind protocol. No significant differences were observed among the mean baseline function studies during the 3 treatment periods. There were no significant differences in sputum production, sputum thickness, dyspnea, or mouth dryness among the 3 treatment periods. Side effects were mild; isoproterenol treatment was associated with an increased frequency of palpitations, and atropine treatment was associated with difficulty in voiding. Significant increases in lung function were apparent in the measurements made 15 min and 60 min after inhalation of atropine or isoproterenol. Mean values of flow and specific airway conductance increased, and mean values of airway resistance and functional residual capacity decreased after inhalation of either drug. There was no significant difference between the effects of atropine and isoproterenol on lung function, although both differed significantly from the effects of placebo (P less than 0.001). Inhaled atropine sulfate was as effective a bronchodilator as inhaled isoproterenol hydrochloride, and was well tolerated during the 3-week trial of daily therapy.", "To examine the mechanisms through which two bronchodilators (theophylline and salbutamol) influence dyspnea during daily activities.\n Twenty-four patients with chronic airflow limitation participated in a multiple crossover, randomized, placebo-controlled trial. The effect of theophylline and salbutamol, alone or combined, on pulmonary function and dyspnea during daily activities was examined. Correlations of changes in forced expiratory volume in 1 second (FEV1) and maximum expiratory pressures (MIPs) (independent variables) and changes in dyspnea score during daily activities (dependent variable) were also examined.\n The two drugs proved to be beneficial the effects in general were additive rather than synergistic. The drugs improved the FEV1; theophylline significantly improved the MIPs. The correlation between the changes in FEV1 and those in dyspnea score, after adjustment for the changes in MIPs, was 0.55 (p less than 0.001). The correlation between the changes in MIPs and those in dyspnea score, after adjustment for the changes in FEV1, was 0.39 (p less than 0.001).\n Changes in airway calibre and in respiratory muscle strength play an independent and important role in dyspnea during daily activities in patients with chronic airflow limitation. Changes in airway calibre may be of greater importance." ]

[ "15351417", "15131430", "12750137", "15827356", "16376249", "9526208", "11685362", "9219134", "9611023", "15022802", "9415907", "9671187", "9855227", "11240535", "9521514", "9113547", "8938608", "15589927", "12678355", "711799", "14657746", "8583450", "12553508", "10959993", "10880936", "12893151", "8371245" ]

[ "Is closed-suction drain necessary in unicompartmental knee replacement? A prospective randomised study.", "A randomized study of closed wound suction drainage for extensive lumbar spine surgery.", "Effect of drain use in the early postoperative period after arthroscopically assisted anterior cruciate ligament reconstruction with bone-patellar tendon-bone graft.", "Effect of drain placed in the donor site in the early postoperative period after arthroscopically assisted anterior cruciate ligament reconstruction with quadrupled hamstring tendons.", "Blood loss after total hip replacement: a prospective randomized study between wound compression and drainage.", "Drainage versus nondrainage in simultaneous bilateral total hip arthroplasties.", "No drainage does not increase complication risk after total knee prosthesis implantation: a prospective, comparative, randomized study.", "Closed wound drainage in shoulder surgery.", "Postoperative drains at the donor sites of iliac-crest bone grafts. A prospective, randomized study of morbidity at the donor site in patients who had a traumatic injury of the spine.", "No need for routine closed suction drainage in elective arthroplasty of the hip: a prospective randomized trial in 104 operations.", "Comparison of closed-suction drainage and no drainage after primary total knee arthroplasty.", "Efficacy of surgical wound drainage in orthopaedic trauma patients: a randomized prospective trial.", "Postoperative drainage of knee arthroplasty is not necessary: a randomized study of 90 patients.", "[A prospective randomized study of wound drainage versus non-drainage in primary total hip or knee arthroplasty].", "Is suction drainage necessary after total joint arthroplasty? A prospective study.", "Efficacy of closed wound drainage after total joint arthroplasty. A prospective randomized study.", "Efficacy of closed wound suction drainage after single-level lumbar laminectomy.", "Wound drainage versus non-drainage for proximal femoral fractures. A prospective randomised study.", "The use of a closed-suction drain in total knee arthroplasty. A prospective, randomised study.", "The use of suction drainage in the operation of meniscectomy.", "The use of postoperative subcutaneous closed suction drainage after posterior spinal fusion in adolescents with idiopathic scoliosis.", "Wound drains in proximal femoral fracture surgery: a randomized prospective trial of 177 patients.", "No effect of drains on the postoperative hematoma volume in hip replacement surgery: a randomized study using scintigraphy.", "Drainage is of no use in primary uncomplicated cemented hip and knee arthroplasty for osteoarthritis: a prospective randomized study.", "[Effectiveness of postoperative drainage after bipolar sealed endoprosthetic arthroplasty for femur neck fracture. Results of a prospective randomized study of 86 cases].", "Arthroscopically assisted ACL reconstruction. Is a drain necessary?", "The effectiveness of suction drainage in total hip arthroplasty." ]

[ "In a prospective randomised trial we evaluated the use of a post-operative closed-suction drain in unicompartmental knee replacement (UKR). Seventy-eight patients were divided into two groups: one without a post-operative closed-suction drain (Group A) and one with a drain (Group B). Both groups were matched for age, sex and pre-operative haemoglobin. In group A we observed a lower day one post-operative analgesic requirement, smaller knee circumference 3 days post-operatively and less local wound complications. Drain usage in UKR resulted in no significant advantage in post-operative pain, range of motion and hospital stay. Post-operative drainage does, however, increase the cost of the procedure both in labour and equipment expenditure. No deep infections occurred in either group during the follow-up period. We conclude that avoiding post-operative closed-suction drainage in UKR does not influence the outcome.", "A prospective randomized study.\n To study the risk of infection, hematoma, and neurologic deficits following extensive lumbar spine surgery in patients with or without prophylactic closed wound suction drain placement.\n One randomized study assessing prophylactic drain placement in one-level lumbar spine surgery suggested that the use of a wound drain is not effective at preventing infection and may actually increase the rate of this complication. Our study was designed to determine the efficacy of closed wound suction drainage in preventing complications after extensive lumbar spine surgery.\n Eighty-three consecutive patients undergoing extensive lumbar spine surgery were prospectively randomized to one of two groups. Forty-two patients had a closed wound suction drain placed before wound closure and 41 patients did not have a drain placed. The two groups were then assessed for differences in postoperative infection rate, incidence of hematoma and neurologic deficits, operating room time, estimated blood loss, hemoglobin and hematocrit values, temperature, dressing drainage, and length of hospital stay. RESULTS.: No infections, epidural hematomas, or new neurologic deficits were encountered in either group of patients. The only significant finding was a higher temperature in the \"no drain\" group the first day after surgery (P = 0.0437).\n Based on the findings in this and other studies, the decision to use or not use a wound drain following lumbar spine surgery should be left to the surgeon's discretion.", "Little data exist on the effect of routine use of postoperative drainage after arthroscopic anterior cruciate ligament reconstruction, although clinical studies of other procedures have not shown benefit to this practice.\n Use of a postoperative drain will not result in decreased suprapatellar girth, increased range of motion, and decreased pain compared with nonuse.\n Prospective randomized clinical trial.\n Twenty-one patients undergoing arthroscopically assisted bone-patellar tendon-bone anterior cruciate ligament reconstruction were randomly assigned to receive a drain for 24 hours (12 patients) or no drain (9 patients). Data for comparison of groups were collected daily through postoperative day 7.\n Pain scores on a visual analog scale demonstrated the same improving trend over time for both treatment and control groups; however, the treatment group had significantly higher average pain scores, except on day 7. Differences in suprapatellar girth, flexion, and extension were not found to be statistically significant between groups.\n Use of a drain after arthroscopically assisted anterior cruciate ligament reconstruction provided no benefit in terms of range of motion, effusion, or pain in the early postoperative period.", "No scientific study has addressed the effects of the routine use of postoperative drains in the donor site after arthroscopic anterior cruciate ligament reconstruction using hamstring tendons.\n Patients who have drains placed in their donor sites have less lower extremity edema, more motion, and more comfort in the early postoperative period.\n Randomized controlled clinical trial; Level of evidence, 1.\n Thirty-four patients undergoing arthroscopically assisted quadruple hamstring tendon anterior cruciate ligament reconstruction were randomly assigned to either receive a drain for 24 hours placed at the donor site (17 patients) or have no drain at the donor site (17 patients). Data were collected on postoperative days 1, 3, 5, and 7 regarding knee flexion, knee extension, thigh circumference, leg circumference, and visual analog scale (measuring pain).\n In the study group versus the control group, there were increased knee flexion measurements on postoperative day 7 (84 degrees vs 69 degrees , P < .05); smaller thigh circumference measurements on postoperative day 7 (36.8 vs 40.1 cm, P < .05); smaller leg circumference measurements on postoperative days 3 (33.2 vs 36.4 cm, P < .05), 5 (32.7 vs 36.0 cm, P < .05), and 7 (31.8 vs 35.7 cm, P < .001); and a lower visual analog scale score on postoperative days 3 (40.38 vs 57.50, P = .001), 5 (38.46 vs 60.35, P = .001), and 7 (38.07 vs 61.43, P = .001).\n Drain placement at the donor site after anterior cruciate ligament reconstruction gives more comfort to the patient and provides better flexion within the first week.", "A randomized, controlled study compared the effects of wound compression with drainage after primary total hip arthroplasty. In 51 patients, an inflatable cuff was placed over the wound underneath a girdle (System Calmed, Calmed AB, Askim, Sweden). Control patients had wound drainage (n = 54). Preoperative and intraoperative variables did not differ between groups. Total blood loss was calculated using hemoglobin balance; with compression it was 1510 +/- 656 mL (mean +/- SD) and in controls 1695 +/- 712 mL (P = .13). However, less blood was transfused in the compression group (P = .05). Wound infection was seen in 2 patients with compression and in 3 controls. Deep venous thrombosis occurred in 3 controls. Wound discharge was more frequent in controls (19/54 vs 8/51; P = .04). Thus, wound compression had no obvious negative effects and reduced wound discharge and need for transfusion. It may replace drainage after total hip arthroplasty.", "A prospective study of 48 patients (96 hips) who had undergone primary simultaneous bilateral total hip arthroplasty was conducted to assess the effect of postoperative suction drainage on wound healing and infection. A suction drain was placed by randomization of the drained versus undrained side. The same surgical technique was used in all total hip arthroplasty wounds. Statistical analysis of the results showed significant differences with respect to drainage from the wound, soaked dressings requiring reinforcements, ecchymosis, and erythema about the wound in the group without drainage. There was no specific correlation between the incidence of wound complications and infection after total hip arthroplasty and the use or nonuse of closed-suction drainage. The hip score and range of motion of the hip were unaffected by the use or nonuse of the drains. The cost of 1 set of hemovac drains is $135 and the cost for 4-5 dressings and bed sheet changes is about $50. Although the hemovac is more expensive, the authors recommend the routine use of suction drains for wounds after primary total hip arthroplasty to reduce drainage, soaked dressings requiring reinforcement, ecchymosis and erythema around the wound, and psychological impact on the patient's fear of bleeding.", "Sixty patients were operated on for primary gonarthrosis by means of a cemented, posterior cruciate preserving total knee and were randomly allocated to postoperative drainage or nondrainage. The primary criterion was duration of hospital stay. Secondary criteria included serial evaluation of knee pain, knee flexion, knee circumference, calculated blood loss after 7 days, complications, reoperations, and the need for blood transfusions. There was no difference between the two groups in any of the criteria during the entire follow-up. There was a nonsignificant trend to a decreased calculated blood loss in the nondrained group and significantly less transfused blood units in the nondrained group. Lack of drainage does not increase complication risk after total knee prosthesis implantation. We therefore recommend using no routine drainage after this procedure.", "To evaluate the effectiveness of closed wound drainage in shoulder surgery, 300 patients were enrolled in a prospective randomized study. Three operations were studied: rotator cuff repair, anterior reconstruction for instability, and arthroplasty. One hundred patients were included in each group. All patients were evaluated for wound hematoma, infection, variation in postoperative rehabilitation caused by wound problems, and length of hospital stay. No statistical difference was found between the patients whose wounds were drained and those whose wounds were not drained. This finding existed within each category. Our data do not support the routine use of closed wound drainage in elective shoulder surgery.", "A prospective, randomized study was performed to assess the effectiveness of postoperative closed suction drainage. One hundred and twelve consecutive procedures involving autologous iliac-crest bone graft were performed, from December 29, 1992, to July 1, 1993, following a traumatic injury of the spine in 108 patients. Sixty of the sites from which the bone graft had been obtained were drained with a single large Hemovac device. The drains were maintained for two to five days postoperatively. The remaining fifty-two incisions were closed without a drainage device. All patients were evaluated clinically for problems with wound-healing. The incisions were considered to be healed when they had been asymptomatic for one year. Of eleven patients who had problems with wound-healing, six had been managed with a drain and five had not. The findings of this study do not support the routine use of drainage at the donor sites of iliac-crest bone grafts.", "The purpose of this study was to determine the utility of closed suction drainage (CSD) in elective total hip arthroplasty (THA).\n We randomized 104 elective, consecutive THAs to receive drainage (53) or no drainage (51). 60 arthroplasties were cemented and 44 hybrid.\n In the drainage group, 2 hematomas and 2 superficial wound infections occurred; there were no wound complications in the undrained group (p = 0.04). Patients receiving drainage had a greater reduction in hematocrit (10.4 vs 7.4) (p = 0.03), and longer hospital stay (5.1 days vs 4.7) (p = 0.01). At the 3-month follow-up, we found no deep wound infections in either group.\n We no longer use CSD in elective, primary, routine THA.", "One hundred thirty-six primary total knee arthroplasty patients were randomized for the use of closed-suction, nonreinfusable wound drains. Blood loss was identical in the drained and undrained groups. Forty percent of undrained wounds compared with 0% of drained wounds required dressing reinforcement. Sixty-nine percent of undrained wounds compared with 39% of drained wounds developed ecchymosis, measuring 92 cm2 in the undrained group and 28 cm2 in the drained group. This study concludes that a simple wound drain effectively minimizes the undesirable accumulation of blood in the surrounding soft tissues and the postoperative wound dressing after total knee arthroplasty.", "To study the efficacy of closed suction drainage in clean nonemergent surgical fracture fixation or bone grafting on the extremities or pelvis.\n A prospective randomized trial.\n The orthopaedic trauma service of a Level I trauma hospital.\n Patients were older than age eighteen years and undergoing clean nonemergent surgical fracture fixation or bone grafting procedures on the extremities (excluding hands and feet) or pelvis.\n The application of a surgical drain.\n Wound drainage, edema, hematoma and erythema, dehiscence, infection, and need for surgery or readmission were followed for six weeks. A univariate analysis with Student's t test for continuous variables and chi-squared analysis for all categorical data were used, with a p value of < or = 0.05 considered statistically significant.\n A total of 202 patients were randomized to 102 patients with no drain and 100 patients with a drain. There was no significant difference between the groups with regard to injury severity, systemic disease, age, body weight, physical status, or estimated blood loss. There was no significant difference between the drain and no-drain groups in any of the parameters evaluated.\n There is no significant difference between drained and nondrained wounds in clean, nonurgent orthopaedic trauma surgery. It appears that drainage systems can be safely eliminated in this group.", "We studied the management of postoperative drainage after total knee replacement (TKR). 90 primary total knee joint arthroplasties were prospectively randomized into 3 groups: a) no drain, b) an autotransfusion system, c) a standard disposable closed suction drainage system. We monitored hemoglobin and hematocrit values, drainage volume and transfusions (homologous and autologous), range of knee motion, knee swelling and hospital stay. Parameters were recorded preoperatively, days 0-8 and 4 months postoperatively. No significant differences were seen between the groups in any of the parameters measured. The results show no benefit from using postoperative drainage systems in knee arthroplasties. Savings of SEK 400 (USD 55) per patient would have resulted if drains had not been used at all.", "Drainage of the operative wound following total hip or knee replacement (THR, TKR) is usually performed to avoid hematoma formation. A certain amount of blood is lost through the drain. The necessity of wound drainage has been questioned, with a view towards blood saving, although most surgeons have not abandoned drainage for fear of local complications. A prospective randomized study was undertaken to compare drainage and non-drainage following THR/TKR in terms of blood-saving and local complications.\n A total of 256 patients undergoing primary THR (152) or TKR (104) were randomly allocated to undergo either suction drainage or no drainage of the wound: there were 76 drained and 76 non-drained THR's, 52 drained and 52 non-drained TKR's. Blood loss was calculated in each patient from the postoperative drop in hematocrit values; the amounts of blood lost intra-operatively and in the drain were also recorded, as was the number of blood units transfused in each patient. Swelling, hip or knee range of motion and wound healing were monitored over the first 6 weeks after operation, and any local or systemic complication was recorded.\n No significant difference was noted between drained and non-drained THR's/TKR's regarding swelling, recovery of hip or knee motion, wound healing, other local or systemic complications. Following THR, no significant difference was noted between calculated blood losses or transfusion requirements in drained versus non-drained patients. Patients with drains lost on average 1 942 ml of blood versus 1 766 ml for non-drained patients; they received on average 1.18 units of transfused blood versus 1.32 units for patients without drains. The differences are not significant. Following TKR, total blood loss was significantly higher in non-drained than in drained patients (1 983 ml versus 1 590 ml) and the amount of blood transfused was also significantly higher in non-drained patients (0.98 unit versus 0.54 unit).\n Following primary hip or knee arthroplasty, the use of wound drainage did not lead to increased blood loss, and non-drainage did not lead to significant wound healing problems but did not reduce blood loss and transfusion requirements. It was even associated, following TKR, with greater blood loss and transfusion. Such data may therefore be used to support drainage as well as non-drainage following THR or TKR. Avoiding drainage may be interesting in terms of cost, but the benefit is marginal; it also eliminates one possible source of retrograde wound infection. Systematic wound drainage following THR or TKR is essentially a tradition. This study shows that it can safely be dispensed with in a number of cases.", "A prospective evaluation of 98 patients who had undergone a total hip or knee arthroplasty was conducted to assess the effect of postoperative suction drainage. Sixty-six patients undergoing elective total hip arthroplasty and 32 patients undergoing total knee replacement were randomly allocated to undergo either suction drainage or no drainage of the wound. Statistical analysis of the results showed no difference in wound healing, severity of wound haematoma, postoperative blood transfusion requirement, range of motion and duration of the hospitalization between the two groups. We conclude that the use of closed suction drainage provides no apparent advantage after uncomplicated total hip or knee arthroplasty.", "The efficacy of closed suction drains following joint arthroplasty operations was prospectively evaluated in a randomized manner. All 88 patients allotted to primary knee or hip arthroplasty operations during a 6-month period were included in the study. Drains were used in 32 of 58 patients following total knee arthroplasty and in 18 of 30 total hip arthroplasties. No statistical difference was found in the hemoglobin levels measured following surgery and in the number of patients requiring blood transfusions between the two groups after total hip arthroplasty (P = .06). The power of the test to detect a difference of 2 g% in hemoglobin levels is 94%. Two patients from each group had a transient serous discharge for 3 to 4 days following surgery and none had wound infections. Significantly more blood transfusions were needed in patients with drains following total knee arthroplasty compared with patients without drains (0.7 unit per patient versus 0.2 unit per patient, P = .005) to maintain the same hemoglobin blood levels. Patients with no drains had significantly more transient sterile serous wound discharge than patients with drains (38.4% vs 12.5%, P = .02). Superficial wound infection necessitating antimicrobial medication developed in one patient with drains and in no patients in the other group. These results suggest that drains may not be needed following total hip arthroplasty. The more common serous wound discharge may be of some concern when drains are not used following total knee arthroplasty.", "The use of closed suction drainage after spinal surgery remains controversial. The purpose of this study was to determine the indications for closed suction drainage after single-level lumbar surgery. Two hundred patients who were scheduled to undergo single-level lumbar surgery without fusion were prospectively randomized into two groups. One group had a closed wound suction drain placed deep to the lumbodorsal fascia before routine closure, whereas the second group had no drain placed. Hemostasis was achieved in all patients before the surgeon had knowledge of the randomization outcome. All drains were removed on the 2nd postoperative day, and the amount of drainage was recorded. After surgery, the patients were evaluated for signs and symptoms of continued wound drainage, hematoma/seroma formation, and/or infection as well as evidence of an acquired neurologic deficit. One hundred three patients had a drain placed before closure and two patients developed postoperative wound infection, both of which were successfully treated with orally administered antibiotics. Of the 97 patients who had no drain placed after the surgical procedure, one patient developed a postoperative wound infection that was treated with surgical incision and drainage, as well as intravenously administered antibiotics. Statistical analysis revealed that the presence or absence of a drain did not affect the postoperative infection rate. No new neurologic deficits occurred in any postoperative patient. The use of drains in single-level lumbar laminectomy without fusion did not affect patient outcome. There was no significant difference in the rate of infection or wound healing and no patient developed a postoperative neurologic deficit.", "The purpose of this prospective randomised study was to examine whether routine drainage in surgery for traumatic hip fractures is useful.\n At the end of surgery for hip fractures, 200 consecutive patients (51 men, 149 women) were randomised to receive suction drainage or not. The status of wound healing was evaluated, with specific reference to haematoma formation or wound infection. Indices of blood loss were the average blood loss during operation, a decrease in the haemoglobin level, fluid collected by the drain, and blood transfusion.\n The severity of wound haematoma and the number of wound infections was not significantly different between the two groups. The average blood loss during operation was 172 ml in the drainage group and 179 ml in the non-drainage group. The volume of drainage fluid was 146 ml. The haemoglobin concentration decreased by 1.4 mg/dl in the drainage group and by 1.3 mg/dl in the non-drainage group (P = 0.83). During admission, 55 patients in the drainage group received 2.5 units of blood and 50 patients in the non-drainage group received 2.7 units.\n The severity of wound haematoma does not lead to statistically significant differences in wound infection rate. The routine use of suction drains may not prevent wound infections.", "We prospectively randomised 100 patients undergoing cemented total knee replacement to receive either a single deep closed-suction drain or no drain. The total blood loss was significantly greater in those with a drain (568 ml versus 119 ml, p < 0.01; 95% CI 360 to 520) although those without lost more blood into the dressings (55 ml versus 119 ml, p < 0.01; 95% CI -70 to 10). There was no statistical difference in the postoperative swelling or pain score, or in the incidence of pyrexia, ecchymosis, time at which flexion was regained or the need for manipulation, or in the incidence of infection at a minimum of five years after surgery in the two groups. We have been unable to provide evidence to support the use of a closed-suction drain in cemented knee arthroplasty. It merely interferes with mobilisation and complicates nursing. Reinfusion drains may, however, prove to be beneficial.", "A prospective trial has been carried out to determine the value of suction drainage in the operation of meniscectomy. One hundred operations were analysed, in half of which drains had been used. The use of the drain could not be shown to result in any sustained advantages. The demand for analgesics after the operation was reduced but not to a statistically significant level. The size of the early effusion was significantly reduced, but this benefit was lost when the knee was mobilised. The return of power to the quadriceps and of movement to the knee were not hastened. The average volume of fluid drained was 134 millilitres and it has been shown that forty-eight hours is a suitable time for removal of the drain. The use of suction drainage is not advocated for the uncomplicated operation of meniscectomy.", "BACKGROUND The purpose of this prospective study was to assess the impact of closed suction drainage on transfusion requirements, frequency of dressing changes, and wound healing following posterior spinal fusion in adolescents with idiopathic scoliosis. METHODS Thirty patients were randomly assigned to one of two groups: drain or no drain. Although the group with drains received more postoperative autologous blood transfusions than the group with no drains (0.88 vs 0.5 unit), the difference was not statistically significant (P = 0.2131). In the undrained group, 58% of the patients had moderate to completely saturated dressings on the second postoperative day compared with only 17% of patients in the drained group. Three of 12 patients in the undrained group demonstrated a wound complication rate compared with no complications in the drained group. CONCLUSION In conclusion, subcutaneous closed suction drainage can improve immediate postoperative wound care without significantly increasing blood loss and transfusion requirements for patients undergoing surgery for idiopathic scoliosis.", "We report on a prospective randomized trial on the effect of wound drains on wound healing following surgery for proximal femoral fractures. One hundred and seventy-seven consecutive patients admitted to Queen's Medical Centre Nottingham, undergoing AO dynamic hip screw (DHS) or hemiarthroplasty were randomized whether or not to receive wound drainage. Wound healing was assessed in terms of ultrasound examination, the ASEPSIS wound score system and overt infection rates. All patients were followed up at 6 weeks and 6 months. Ultrasound examinations showed that drains were indeed ineffective in preventing haematoma formation, the first time this has been demonstrated objectively. However, using drains failed to prevent late seroma formation. Patients who received wound drainage showed statistically better wound healing on the ASEPSIS wound scoring system and a reduced infection rate. The ASEPSIS scores on day 2 and 5 postoperatively proved an accurate predictor of poor wound healing. This study conflicts with previous smaller studies which failed to show an effect of wound drainage upon wound healing, and strongly supports the use of wound drains.", "In a prospective randomized study we used erythrocyte scintigraphy to evaluate whether drainage reduced the hematoma volume after total hip arthroplasty. 12 patients were left without drains and 10 patients had two drains inserted, one below the fascia and one subcutaneously. We used tomographic registration (SPECT) to calculate the volume of the hematoma (erythrocytes) about 22 hours after surgery and found that drainage did not reduce the volume, but increased the need for blood transfusion.", "In a prospective, randomized study, 58 patients with primary cemented hip arthroplasty and 39 patients with primary cemented knee arthroplasty were divided into groups with postoperative closed-suction drainage and without drainage. There was no difference in healing of the wounds, postoperative blood transfusions, complications, or range of motion. Although there was more soaked dressing requiring reinforcements in the groups without drainage, as a result of this study, we no longer use drains in uncomplicated cemented primary hip and knee arthroplasties for osteoarthritis.", "nan", "We report on the results of a prospective randomised controlled trial to evaluate the use of an intra-articular drain following arthroscopically assisted ACL reconstruction using patellar tendon autograft. Forty-nine patients were recruited for the trial and randomised into receiving or not receiving a drain following surgery. An independent observer who was blinded for the use of the drain assessed the knees for swelling, range of movement (ROM) and pain at 2, 4 and 6 weeks postoperatively. Muscle strength was assessed at 12 weeks following surgery using the KIN COM III isometric dynamometer. We found that the knees that were drained following surgery initially had less swelling and a better ROM. However, at 4 weeks this difference had disappeared. At 3 and 6 months, there was no functional difference between the two groups. We recommend that no drain be used following ACL reconstruction as removal of the drain is uncomfortable and carries theoretical and avoidable risks.", "nan" ]

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[ "Mechanical bowel preparation or not? Outcome of a multicenter, randomized trial in elective open colon surgery.", "Requirement for bowel preparation in colorectal surgery.", "Rectal cancer surgery with or without bowel preparation: The French GRECCAR III multicenter single-blinded randomized trial.", "Mechanical bowel preparation for elective colorectal surgery: a multicentre randomised trial.", "The influence of mechanical bowel preparation in elective lower colorectal surgery.", "[Mechanical preparation in elective colorectal surgery, a usual practice or a necessity?].", "Randomized clinical trial of mechanical bowel preparation versus no preparation before elective left-sided colorectal surgery.", "Randomized clinical trial of bowel preparation with a single phosphate enema or polyethylene glycol before elective colorectal surgery.", "Colon and rectal surgery without mechanical bowel preparation: a randomized prospective trial.", "Is mechanical bowel preparation mandatory for elective colon surgery? A prospective randomized study.", "Mechanical bowel preparation for elective colorectal surgery with primary intraperitoneal anastomosis by a single surgeon: interim analysis of a prospective single-blinded randomized trial.", "Bowel preparation with oral polyethylene glycol electrolyte solution vs. no preparation in elective open colorectal surgery: prospective, randomized study.", "Colon and rectal surgery for cancer without mechanical bowel preparation: one-center randomized prospective trial.", "Multicentre randomized clinical trial of mechanical bowel preparation in elective colonic resection." ]

[ "Mechanical bowel preparation is common practice in elective colon surgery. In recent literature the value of this procedure is under discussion. To verify the value of mechanical bowel preparation in elective open colon surgery, a randomized clinical trial was conducted.\n During a prospective, multicenter, randomized study, 250 patients undergoing elective open colon surgery were randomized between receiving mechanical bowel preparation with polyethylene glycol (PEG group, 125 patients) and having a normal meal preoperatively (normal meal preoperatively group, 125 patients). Outcome parameters were wound infection with bacterial results of intraoperative swabs and anastomotic leak.\n In the polyethylene glycol group there were a total of nine wound infections (7.2 percent) and seven anastomotic leaks (5.6 percent) compared with seven wound infections (5.6 percent) (P = 0.61) and six anastomotic leaks (4.8 percent) (P = 0.78) in the normal meal preoperatively group. Bacterial results showed 52 percent sterile subcutis swabs in the PEG group and 63 percent sterile subcutis swabs in the normal meal preoperatively group (P = 0.11).\n In the present study we could not detect a difference in outcome parameters between patients receiving mechanical bowel preparation in elective open colon surgery and patients without preoperative treatment of the bowel. The present study, although underpowered, did not show a difference in the primary outcome of bacterial wound cultures between patients receiving preoperative mechanical bowel preparation and patients receiving no preoperative bowel treatment. We conclude that there may be no need to continue the use of mechanical bowel preparation in elective open colon surgery.", "To determine whether mechanical bowel preparation influences the incidence of anastomotic dehiscence following colorectal surgery, 186 patients undergoing elective left colonic or rectal resection were randomized before surgery to bowel preparation (n = 89) or no bowel preparation (n = 97). Surgical technique was standardized and no patient had a defunctioning colostomy. Seventeen patients were excluded (seven with preparation, ten without). Indications for surgery in the remaining 169 patients were carcinoma (133 patients), diverticular disease (26), inflammatory bowel disease (six) and miscellaneous conditions (four). Operations performed were left colonic resection or reversal of Hartmann's procedure (26 with preparation, 28 without) and anterior resection (56 versus 59). The overall morbidity rate (18 per cent) was similar in the two groups. All seven clinical anastomotic leaks occurred after low anterior resection, in three of the 39 patients who had undergone bowel preparation and four of the 36 who had not (P > 0.9). Two deaths occurred, both of patients who had received bowel preparation, one being secondary to anastomotic leakage. Bowel preparation does not influence outcome after elective colorectal surgery.", "To assess with a single-blinded, multicenter, randomized trial, the postoperative results in patients undergoing sphincter-saving rectal resection for cancer without preoperative mechanical bowel preparation (MBP).\n The collective evidence from literature strongly suggests that MBP, before elective colonic surgery, is of no benefit in terms of postoperative morbidity. Very few data and no randomized study are available for rectal surgery and preliminary results conclude toward the safety of rectal resection without MBP.\n From October 2007 to January 2009, patients scheduled for elective rectal cancer sphincter-saving resection were randomized to receive preoperative MBP (ie, retrograde enema and oral laxatives) or not. Primary endpoint was the overall 30-day morbidity rate. Secondary endpoints included mortality rate, anastomotic leakage rate, major morbidity rate (Dindo III or more), degree of discomfort for the patient, and hospital stay.\n A total of 178 patients (103 men), including 89 in both groups (no-MBP and MBP groups), were included in the study. The overall and infectious morbidity rates were significantly higher in no-MBP versus MBP group, 44% versus 27%, P = 0.018, and 34% versus 16%, P = 0.005, respectively. Regarding both anastomotic leakage and major morbidity rates, there was no significant difference between no-MBP and MBP group: 19% versus 10% (P = 0.09) and 18% versus 11% (P = 0.69), respectively. Moderate or severe discomfort was reported by 40% of prepared patients. Mortality rate (1.1% vs 3.4%) and mean hospital stay (16 vs 14 days) did not differ significantly between both groups.\n This first randomized trial demonstrated that rectal cancer surgery without MBP was associated with higher risk of overall and infectious morbidity rates without any significant increase of anastomotic leakage rate. Thus, it suggests continuing to perform MBP before elective rectal resection for cancer.", "Mechanical bowel preparation is a common practice before elective colorectal surgery. We aimed to compare the rate of anastomotic leakage after elective colorectal resections and primary anastomoses between patients who did or did not have mechanical bowel preparation.\n We did a multicentre randomised non-inferiority study at 13 hospitals. We randomly assigned 1431 patients who were going to have elective colorectal surgery to either receive mechanical bowel preparation or not. Patients who did not have mechanical bowel preparation had a normal meal on the day before the operation. Those who did were given a fluid diet, and mechanical bowel preparation with either polyethylene glycol or sodium phosphate. The primary endpoint was anastomotic leakage, and the study was designed to test the hypothesis that patients who are given mechanical bowel preparation before colorectal surgery do not have a lower risk of anastomotic leakage than those who are not. The median follow-up was 24 days (IQR 17-34). We analysed patients who were treated as per protocol. This study is registered with ClinicalTrials.gov, number NCT00288496.\n 77 patients were excluded: 46 who did not have a bowel resection; 21 because of missing outcome data; and 10 who withdrew, cancelled, or were excluded for other reasons. The rate of anastomotic leakage did not differ between both groups: 32/670 (4.8%) patients who had mechanical bowel preparation and 37/684 (5.4%) in those who did not (difference 0.6%, 95% CI -1.7% to 2.9%, p=0.69). Patients who had mechanical bowel preparation had fewer abscesses after anastomotic leakage than those who did not (2/670 [0.3%] vs 17/684 [2.5%], p=0.001). Other septic complications, fascia dehiscence, and mortality did not differ between groups.\n We advise that mechanical bowel preparation before elective colorectal surgery can safely be abandoned.", "This study evaluates the effects of mechanical bowel preparation (MBP) on anastomosis below the peritoneal verge and questions the influence of MBP on anastomotic leakage in combination with a diverting ileostomy in lower colorectal surgery.\n In a previous large multicenter randomized controlled trial MBP has shown to have no influence on the incidence of anastomotic leakage in overall colorectal surgery. The role of MBP in lower colorectal surgery with or without a diverting ileostomy remains unclear.\n This study is a subgroup analysis of a prior multicenter (13 hospitals) randomized trial comparing clinical outcome of MBP versus no MBP. Primary end point was the occurrence of anastomotic leakage and secondary endpoints were septic complications and mortality.\n Total of 449 Patients underwent a low anterior resection with a primary anastomosis below the peritoneal verge. The incidence of anastomotic leakage was 7.6% for patients who received MBP and 6.6% for patients who did not. Significant risk factors for anastomotic leakage were the American Society of Anesthesiologists-classification (P = 0.005) and male gender (P = 0.007). Of total, 48 patients received a diverting ileostomy during initial surgery; 27 patients received MBP and 21 patients did not. There were no significant differences regarding septic complications and mortality between both groups.\n MBP has no influence on the incidence of anastomotic leakage in low colorectal surgery. Furthermore, omitting MBP in combination with a diverting ileostomy has no influence on the incidence of anastomotic leakage, septic complications, and mortality rate.", "Pre-operative preparation of the colon is carried out with oral and/or intravenous administration of antibiotics and through the mechanical preparation of the colon using various substances to decrease the intraluminal bacterial concentration and remove the larger quantity of fecal material as possible, thus decreasing the risk of anastomosis dehiscence due to an increase in the intraluminal pressure. The role of antibiotics has been completely established while that of mechanical preparation is still questioned. The objective of this study is to assess the actual impact of mechanical preparation on colorectal surgery.\n Forty seven patients who underwent elective colorectal surgery were prospectively evaluated, out of which only 24 had mechanical preparation. We compared variables such as age, sex, preoperative hemoglobin, albumin and leukocyte values, surgery characteristics and type of anastomosis, as well as complications in both groups. Results: We found a higher incidence of fistulas, dehiscences and general complications in the group undergoing mechanical preparation of the colon.\n The results show that mechanical preparation of the colon does not provide any benefit and may result in a higher incidence of complications in colorectal surgery.", "Mechanical bowel preparation (MBP) is performed routinely before colorectal surgery to reduce the risk of postoperative infectious complications. The aim of this randomized clinical trial was to compare the outcome of patients who underwent elective left-sided colorectal surgery with or without MBP.\n Patients scheduled for elective left-sided colorectal resection with primary anastomosis were randomized to preoperative MBP (3 litres of polyethylene glycol) (group 1) or surgery without MBP (group 2). Postoperative abdominal infectious complications and extra-abdominal morbidity were recorded prospectively.\n One hundred and fifty-three patients were included in the study, 78 in group 1 and 75 in group 2. Demographic, clinical and treatment characteristics did not differ significantly between the two groups. The overall rate of abdominal infectious complications (anastomotic leak, intra-abdominal abscess, peritonitis and wound infection) was 22 per cent in group 1 and 8 per cent in group 2 (P = 0.028). Anastomotic leak occurred in five patients (6 per cent) in group 1 and one (1 per cent) in group 2 (P = 0.210) [corrected] Extra-abdominal morbidity rates were 24 and 11 per cent respectively (P = 0.034). Hospital stay was longer for patients who had MBP (mean(s.d.) 14.9(13.1) versus 9.9(3.8) days; P = 0.024).\n Elective left-sided colorectal surgery without MBP is safe and is associated with reduced postoperative morbidity.", "A recent meta-analysis has questioned the value of bowel preparation in patients undergoing colorectal resection. The aim of this clinical trial was to evaluate whether a single phosphate enema was as effective as oral polyethylene glycol (PEG) solution in preventing anastomotic leakage.\n Patients were randomized to receive either a single phosphate enema or 3 litres of oral PEG solution before surgery. Patients were followed for a minimum of 6 weeks to detect anastomotic leakage.\n There were 147 patients in each group and the groups were evenly matched for putative risk factors at baseline. Patients in the enema group had more anastomotic leaks requiring reoperation than those in the PEG group (4.1 versus 0 per cent, P = 0.013; relative risk 2.04 (95 per cent confidence interval (c.i.) 1.82 to 2.30)). The mortality rate was higher in the PEG group (2.7 versus 0.7 per cent, P = 0.176; odds ratio 1.62 (95 per cent c.i. 0.45 to 36.98)).\n Bowel preparation with a phosphate enema was associated with an increased risk of anastomotic leakage requiring reoperation compared with oral PEG. These results do not support the routine use of a phosphate enema in patients undergoing elective colorectal surgery.", "To assess whether elective colon and rectal surgery can be safely performed without preoperative mechanical bowel preparation.\n Mechanical bowel preparation is routinely done before colon and rectal surgery, aimed at reducing the risk of postoperative infectious complications. However, in cases of penetrating colon trauma, primary colonic anastomosis has proven to be safe even though the bowel is not prepared.\n Patients undergoing elective colon and rectal resections with primary anastomosis were prospectively randomized into two groups. Group A had mechanical bowel preparation with polyethylene glycol before surgery, and group B had their surgery without preoperative mechanical bowel preparation. Patients were followed up for 30 days for wound, anastomotic, and intra-abdominal infectious complications.\n Three hundred eighty patients were included in the study, 187 in group A and 193 in group B. Demographic characteristics, indications for surgery, and type of surgical procedure did not significantly differ between the two groups. Colo-colonic or colorectal anastomosis was performed in 63% of the patients in group A and 66% in group B. There was no difference in the rate of surgical infectious complications between the two groups. The overall infectious complications rate was 10.2% in group A and 8.8% in group B. Wound infection, anastomotic leak, and intra-abdominal abscess occurred in 6.4%, 3.7%, and 1.1% versus 5.7%, 2.1%, and 1%, respectively.\n These results suggest that elective colon and rectal surgery may be safely performed without mechanical preparation.", "Bowel preparation prior to colonic surgery usually includes antibiotic therapy together with mechanical bowel preparation (MBP). Mechanical bowel preparation may cause discomfort to the patient, prolonged hospitalization, and water and electrolyte imbalance. It was assumed that with the improvement in surgical technique together with the use of more effective prophylactic antibiotics, it was possible that MBP would no longer be necessary.\n There is no statistical difference in the postoperative results of patients who undergo elective colon resection with MBP as compared with those who have no MBP. Design and\n The study includes all patients who had elective large bowel resection at Campus Golda between April 1, 1999, and March 31, 2002. Emergency operations were not included. The patients were randomly assigned to the 2 study groups (with or without MBP) according to identification numbers. All patients were treated with intravenous and oral antibiotics prior to surgery. The patients in the MBP group received Soffodex for bowel preparation.\n A total of 329 patients participated in the study, 165 without MBP and 164 with MBP. The 2 groups were similar in age, sex, and type of surgical procedure. Two hundred sixty-eight patients (81.5%) underwent surgery owing to colorectal cancer and 61 patients (18.5%) owing to benign disease. The hospitalization period was longer in the bowel-prepared group (mean +/- SD, 8.2 +/- 5.1 days) as compared with the nonprepared group (mean +/- SD, 8.0 +/- 2.7 days). However, this difference was not statistically significant. The time until the first bowel movement was similar between the 2 groups: a mean +/- SD of 4.2 +/- 1.3 days in the nonprepared group as compared with a mean +/- SD of 4.3 +/- 1.1 days in the prepared group (P = NS). Four patients (1.2%) died in the postoperative course owing to acute myocardial infarction and pulmonary embolism. Sixty-two patients (37.6%) of the non-MBP group suffered from postoperative complications as compared with 77 patients (46.9%) of the MBP group.\n Our results suggest that no advantage is gained by preoperative MBP in elective colorectal surgery.", "We report an interim analysis of a prospective single-blinded randomized trial designed to investigate whether preoperative mechanical bowel preparation influences the rate of surgical-site infection and anastomotic failure after elective colorectal surgery with primary intraperitoneal anastomosis performed by a single surgeon. Patients scheduled to undergo an elective colorectal procedure with a primary intraperitoneal anastomosis were randomized to receive either oral polyethylene glycol lavage solution and enemas (group A) or no preparation (group B). Surgical-site infection and anastomotic failure were investigated. Of 97 patients included, 48 were assigned to group A and 49 to group B. Twelve (12.4%) developed wound infections, six in each group (12.5 vs. 12.2%; NS). Intra-abdominal sepsis was only seen in group A (n = 3, 6.3%). Anastomotic failure occurred in four patients in group A (8.3%) vs. two patients in group B (4.1%) (NS). The overall complication rate in group A was 27.1%, vs. 16.3% in group B. The number needed to harm was 9.3. Our interim analysis of a prospective single-blinded randomized trial suggests that a surgeon may have the same or even worse outcomes when mechanical bowel preparation is routinely used for colorectal surgery with primary intraperitoneal anastomosis.", "Efficient mechanical bowel preparation has been regarded as essential in preventing postoperative complications of colorectal surgery, but the necessity of bowel cleansing has been disputed recently. The aim of this study was to evaluate the outcome of elective colorectal surgery in patients with or without bowel preparation.\n Altogether, 267 consecutive adult patients admitted for elective open colorectal surgery were randomly assigned either to the bowel preparation group with oral polyethylene glycol electrolyte solution (138 patients) or no preparation group (129 patients). Patients who were unable to drink polyethylene glycol electrolyte solution, those who had had bowel preparation within the previous week, and patients not needing opening of the bowel were excluded. Routine colorectal surgery was undertaken, and infectious and other complications were registered daily. Late complications were checked up one to two months after surgery.\n No deaths were recorded, and 76 percent of the patients in the polyethylene glycol electrolyte solution group and 81 percent in the unprepared group recovered without complication. Anastomotic leaks occurred in 4 percent of the polyethylene glycol electrolyte solution patients and in 2 percent of the other cases, and other surgical site infections occurred in 6 and 5 percent, respectively. None of the differences was statistically significant. There was no difference in restoration of bowel function. The median postoperative stay was eight days in both groups.\n Preoperative bowel preparation seems to offer no benefit in elective open colorectal surgery.", "Mechanical bowel preparation is routinely done before colon and rectal surgery, aimed at reducing the risk of postoperative infectious complications. The aim of the study was to assess whether elective colon and rectal surgery can be safely performed without preoperative mechanical bowel preparation.\n Patients undergoing elective colon and rectal resections with primary anastomosis were prospectively randomized into two groups. Group A had mechanical bowel preparation with polyethylene glycol before surgery, and group B had their surgery without preoperative mechanical bowel preparation. Patients were followed up for 30 days for wound, anastomotic, and intra-abdominal infectious complications.\n Two hundred forty four patients were included in the study, 120 in group A and 124 in group B. Demographic characteristics, type of surgical procedure and type of anastomosis did not significantly differ between the two groups. There was no difference in the rate of surgical infectious complications between the two groups but the overall infectious complications rate was 20.0% in group A and 11.3% in group B (p .05). Wound infection (p = 0.18), anastomotic leak (p = 0.52), and intra-abdominal abscess (p = 0.36) occurred in 9.2%, 5.8%, and 5.0% versus 4.8%, 4.0%, and 2.4%, respectively. No mechanical bowel preparation seems to be safe also in rectal surgery.\n These results suggest that elective colon and rectal surgery may be safely performed without mechanical preparation.", "Recent studies have suggested that MBP does not lower the risk of postoperative septic complications after elective colorectal surgery. This randomized clinical trial assessed whether preoperative MBP is beneficial in elective colonic surgery.\n A total of 1505 patients, aged 18-85 years with American Society of Anesthesiologists grades I-III, were randomized to MBP or no MBP before open elective surgery for cancer, adenoma or diverticular disease of the colon. Primary endpoints were cardiovascular, general infectious and surgical-site complications within 30 days, and secondary endpoints were death and reoperations within 30 days.\n A total of 1343 patients were evaluated, 686 randomized to MBP and 657 to no MBP. There were no significant differences in overall complications between the two groups: cardiovascular complications occurred in 5.1 and 4.6 per cent respectively, general infectious complications in 7.9 and 6.8 per cent, and surgical-site complications in 15.1 and 16.1 per cent. At least one complication was recorded in 24.5 per cent of patients who had MBP and 23.7 per cent who did not.\n MBP does not lower the complication rate and can be omitted before elective colonic resection. Registration number: ISRCTN28535118 (http://www.controlled-trials.com).\n (c) 2007 British Journal of Surgery Society Ltd." ]

[ "15196155", "17444382", "9360253", "12015689", "11451697", "1663466", "10150324", "1662638", "7205167", "15917519", "12386036", "1390144", "15843702", "8678103", "15302637", "16229991", "9589816", "12182257", "16201937" ]

[ "Intramuscular bipenicillin vs. intravenous penicillin in the treatment of erysipelas in adults: randomized controlled study.", "Can cycloidal vibration plus standard treatment reduce lower limb cellulitis treatment times?", "Antibiotic and prednisolone therapy of erysipelas: a randomized, double blind, placebo-controlled study.", "Once-daily intravenous cefazolin plus oral probenecid is equivalent to once-daily intravenous ceftriaxone plus oral placebo for the treatment of moderate-to-severe cellulitis in adults.", "Once-daily oral gatifloxacin versus oral levofloxacin in treatment of uncomplicated skin and soft tissue infections: double-blind, multicenter, randomized study.", "Azithromycin, erythromycin and cloxacillin in the treatment of infections of skin and associated soft tissues. European Azithromycin Study Group.", "Ampicillin/sulbactam versus cefazolin or cefoxitin in the treatment of skin and skin-structure infections of bacterial etiology.", "Double-blind, double-dummy comparison of azithromycin and cephalexin in the treatment of skin and skin structure infections.", "Efficacy of two dosage schedules of cephalexin in dermatologic infections.", "Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections.", "Oral pristinamycin versus standard penicillin regimen to treat erysipelas in adults: randomised, non-inferiority, open trial.", "Roxithromycin versus penicillin in the treatment of erysipelas in adults: a comparative study.", "Flucloxacillin alone or combined with benzylpenicillin to treat lower limb cellulitis: a randomised controlled trial.", "Current and future management of serious skin and skin-structure infections.", "Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis.", "Sequential intravenous/oral moxifloxacin versus intravenous piperacillin-tazobactam followed by oral amoxicillin-clavulanate for the treatment of complicated skin and skin structure infection.", "Cefdinir versus cephalexin for the treatment of skin and skin-structure infections. The Cefdinir Adult Skin Infection Study Group.", "Randomized, double-blind, multicenter comparison of oral cefditoren 200 or 400 mg BID with either cefuroxime 250 mg BID or cefadroxil 500 mg BID for the treatment of uncomplicated skin and skin-structure infections.", "Meropenem versus imipenem-cilastatin for the treatment of hospitalized patients with complicated skin and skin structure infections: results of a multicenter, randomized, double-blind comparative study." ]

[ "The objective of the study was to evaluate the efficacy of intramuscular penicillin: mixture of benzyl penicillin and procain penicillin (2 MU x 2 times daily) and intravenous benzyl penicillin (4 MU x 6 times daily) in the treatment of hospitalized adult patients with erysipelas. A prospective randomized unicentric trial was conducted. In total, 112 patients entered the study; 57 in the intramuscular group and 55 patients in the intravenous group completed the trial. The failure rate was 14% for intramuscular group and 20% for the intravenous group (P = 0.40). Local complications such as of the leg abscesses were observed in the two groups (intravenous 9.1%, intramuscular 7%; P = 0477). Of the patients treated with intravenous benzyl penicillin, 25.5% presented complications related to the route (venitis). Intramuscular penicillin should be considered an effective and well-tolerated treatment of erysipelas in adult patients.", "This single-centre non-blind randomised controlled trial aimed to compare clinical outcomes in terms of recovery time of standard treatment of lower limb cellulitis versus standard treatment combined with cycloidal vibration (Vibro-Pulse) therapy.\n Thirty-six patients (18 per group) with lower limb cellulitis were randomised to receive either standard treatment (intravenous or oral antibiotic therapy) and bed rest or standard treatment combined with cycloidal vibration treatment three times per day, 30 minutes per treatment. The outcome measure was the daily amount of reduction in erythema/cellulitis and oedema reduction against time for up to seven days of treatment and the resources required.\n There was a clinically significant difference between the two groups, with 66% of the study group fully recovering within the seven days compared with 11% of the control group.\n Cycloidal vibration combined with standard therapy can significantly reduce cellulitis treatment time. This can reduce both hospital bed days and the resources required.", "112 patients admitted to hospital with a diagnosis of erysipelas, were randomized to 8 days treatment with prednisolone or placebo in addition to antibiotics. 108 patients received the study drugs and were evaluated for time to cure, which was the primary end-point. The median healing time was significantly shorter in the prednisolone group, 5 days, vs 6 days in the placebo group (p < 0.01). The 90th percentile healing time was 10.0 days in the prednisolone group vs 14.6 days in the control group. The prednisolone-treated patients had a median length of hospital stay (secondary end-point) of 5 days vs 6 for the placebo-treated (p < 0.01). The median treatment time with intravenous antibiotics (secondary end-point) was 4 days in the placebo group, which was 1 day longer than in the prednisolone group (p < 0.05). 13 patients, 7 of whom received placebo, relapsed during the observation period of 3 weeks. The frequency of side effects attributable to the study drug was not higher in the prednisolone group.", "A once-daily regimen of cefazolin (2 g intravenously [iv]) plus probenecid (1 g by mouth) was compared with a once-daily regimen of ceftriaxone (1 g iv) plus oral placebo in a randomized, double-blind equivalence trial of home-based therapy for moderate-to-severe cellulitis in adults. For the assessable recipients of cefazolin-probenecid (n=59) and ceftriaxone-placebo (n=57), clinical cure occurred at the end of treatment in 86% and 96% (P=.11), respectively, and was maintained at 1 month of follow-up in 96% and 91% (P=.55), respectively. The mean number of treatment doses (+/-standard deviation) given was similar in the 2 treatment arms (6.97+/-2.6 for cefazolin-probenecid and 6.12+/-2.1 for ceftriaxone-placebo; P=.06). The median antibiotic trough concentrations were 2.35 microgram/mL for cefazolin and 15.45 microgram/mL for ceftriaxone. Patients in the 2 treatment arms were similar with regard to overall rates of adverse reaction (P=.15), but nausea was more common among those in the cefazolin-probenecid arm (P=.048). The once-daily regimen of cefazolin-probenecid is a cheap, practical, and effective treatment option for moderate-to-severe cellulitis, and it avoids the need to use third-generation cephalosporins in most patients.", "This was a double-blind, multicenter study in which 410 adults (> or =18 years of age) with uncomplicated skin and soft tissue infections (SSTIs) were randomized to receive either 400 mg of gatifloxacin orally once daily or 500 mg of levofloxacin orally once daily for 7 to 10 days. The study protocol called for four assessments-before and during treatment, at the end of treatment, and posttreatment. Efficacy evaluations included clinical response and bacterial eradication rates. Of 407 treated patients, 202 (108 women, 94 men) received gatifloxacin and 205 (111 women, 94 men) received levofloxacin. For clinically evaluable patients, the cure rates were 91% for gatifloxacin and 84% for levofloxacin (95% confidence interval [CI] for the difference, -2.0 to 15.2%). Clinical cure rates for microbiologically evaluable patients were 93% for gatifloxacin and 88% for levofloxacin (95% CI for the difference, -6.5 to 16.8%). The bacterial eradication rate was 92% for each group, with gatifloxacin eradicating 93% of the methicillin-susceptible Staphylococcus aureus isolates and levofloxacin eradicating 91% of them. Both drugs were well tolerated. Most of the adverse events were mild to moderate, and nausea was the most common adverse event in each treatment arm. Once-daily oral gatifloxacin (400 mg) is clinically efficacious and well tolerated compared with once-daily levofloxacin (500 mg) for the treatment of patients with uncomplicated SSTIs.", "Azithromycin (total dose 1.5 g) given orally in five or six doses over 5 days was compared with erythromycin and cloxacillin both given orally as 500 mg four times daily for 7 days in two multicentre studies of patients with skin and associated soft-tissue infections. Azithromycin eradicated baseline pathogen(s), mainly Staphylococcus aureus, in 89% compared with in 78%, of erythromycin-treated patients (P = 0.501) and in 78% compared with in 59% of cloxacillin-treated patients (P = 0.421). No statistically significant difference in clinical cure was reported between azithromycin (74%) and erythromycin (75%, P = 1.00) and between azithromycin (60%) and cloxacillin (47%, P = 0.301) treatment groups. The side-effects reported for azithromycin were mainly mild or moderate gastro-intestinal complaints and there were no major abnormalities in laboratory parameters. It is concluded that azithromycin was as effective as, but better tolerated than, either erythromycin or cloxacillin and short-course therapy may improve patient compliance.", "This randomized, double-blind study compared 1 g of ampicillin plus 0.5 g of sulbactam with 0.5 g of cefazolin in the treatment of cellulitis and with 1 g of cefoxitin in other skin and skin-structure infections. Study drugs were administered intravenously every 6 hours to 58 hospitalized patients. Each indication was evaluated separately. In cellulitis, ampicillin/sulbactam and cefazolin produced clinical cure or improvement in 100% and 91.7% of patients, respectively; duration of hospitalization was 7.7 and 7.2 days. In other skin and skin-structure infections, results for ampicillin/sulbactam and cefoxitin, respectively, were clinical cure or improvement, 80% and 64.7%; treatment failures, 0% and 11.8%; bacterial eradication, 40% and 53%; and duration of hospitalization, 7.7 and 9.4 days. No unusual or unexpected adverse experiences related to any study drug occurred. One patient treated with ampicillin/sulbactam died of a pulmonary embolism, and 1 patient treated with cefoxitin was discontinued from the study following amputation of an infected foot. These events were not considered drug-related. The treatment groups showed no statistically significant differences in efficacy or safety.", "In this double-blind, randomised trial conducted in 22 centres in the USA, azithromycin given over five days, as a once-a-day regimen, (500 mg on day 1, 250 mg on days 2-5) was compared with cephalexin (500 mg b.i.d.) given for ten days in the treatment of patients with skin and skin structure infections. A total of 366 patients entered the study and 179 of these were eligible for the efficacy analysis. The overall clinical response to azithromycin was 94.0%, compared with 95.8% for cephalexin. The clinical cure rates were 53.0% for azithromycin and 59.4% for cephalexin; the respective improvement rates were 41.0% and 36.5%. Distribution of response (cured, improved, failed) was similar in each group (p = 0.37). The bacteriological eradication rate for azithromycin-treated patients was 94.2% and for cephalexin-treated patients was 90.3% (p = 0.34). Clinical and bacteriological response was similar in each group for all primary diagnoses. The two antibiotics were well tolerated, the overall incidence of side effects being 13.7% with approximately 60% due to gastrointestinal disturbances. In all but one case (cephalexin) the severity of the reported side effects was mild or moderate. Six patients withdrew from the study due to treatment-related events; five had been treated with azithromycin and one with cephalexin. In summary, a five-day, once-daily regimen of azithromycin was as effective as a ten-day, twice-daily regimen of cephalexin in the treatment of patients with skin and skin structure infections.", "Is the administration of oral antibiotics four times a day as necessary as some pharmacokinetic studies indicate? The efficacy of cephalexin administered twice a day was compared to the same drug administered four times a day for the treatment of skin and skin structure infections due to staphylococcus and/or streptococcus. The 154 outpatients in this four-clinic study ranged in age from 1 month to more than 70 years. A random number table was used to assign patients to either the twice a day or the four times a day regimen. The total daily dosage was the same in each regimen. Administration twice a day proved equally effective to the four times a day regimen. Both regimens were more than 97 percent effective and side effects were minimal.", "Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (P=0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (P<0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA.", "To assess the efficacy and safety of oral pristinamycin versus intravenous then oral penicillin to treat erysipelas in patients in hospital.\n Multicentre, parallel group, open labelled, randomised non-inferiority trial.\n 22 French hospitals.\n 289 adults admitted to hospital with erysipelas.\n At follow up (day 25-45) the cure rate (primary efficacy end point) for the per protocol populations was 81% (83/102) for pristinamycin and 67% (68/102) for penicillin. The planned interim analysis (global one sided type I error 5%) showed that the one sided 97.06% confidence interval of the observed difference (pristinamycin-penicillin) between cure rates (3.3% to infinity ) exceeded the -10% non-inferiority threshold. For the intention to treat populations the cure rate at follow up was 65% (90/138) for pristinamycin and 53% (79/150) for penicillin, with the one sided 97.06% confidence interval of the observed difference between cure rates (1.7% to infinity ) exceeding the -10% non-inferiority threshold. That the lower limit of the confidence interval exceeded the -10% threshold and was also >0 supports the hypothesis that pristinamycin is significantly superior at the 5% level. More adverse events related to treatment, as assessed by the investigators, were reported in the pristinamycin group than in the penicillin group. Most adverse events involved the gastrointestinal tract (nausea, vomiting, and diarrhoea) but were minor and usually did not require discontinuation of treatment.\n Pristinamycin could be an alternative to the standard intravenous then oral penicillin regimen used to treat erysipelas in adults in hospital, with the advantages of oral first line therapy.", "A prospective, randomized, multicentre trial was conducted to evaluate the efficacy and safety of roxithromycin (150 mg b.i.d. orally) and penicillin (2.5 MU x 8 daily intravenously, then 6 MU daily orally) in the treatment of hospitalized adult patients with erysipelas. Seventy-two patients entered the study. Thirty-one patients in the roxithromycin group and 38 patients in the penicillin group completed the trial. The overall efficacy rates (cure without additional antibiotics) were 84% (26/31) in the roxithromycin group and 76% (29/38) in the penicillin group (P = 0.43). No side-effects were observed in the roxithromycin-treated patients whereas rashes occurred in two cases in the penicillin group, leading to exclusion from the study. Oral roxithromycin can thus be considered an effective and well-tolerated treatment for erysipelas in adult hospitalized patients.", "To determine whether using intravenous benzylpenicillin in addition to intravenous flucloxacillin would result in a more rapid clinical response in patients with lower limb cellulitis.\n This was a randomised controlled trial set in an inner city teaching hospital, comprising 81 patients with lower limb cellulitis requiring intravenous antibiotics. The main outcome measure was the mean number of doses of antibiotic required until clinical response.\n The mean number of doses required was 8.47 (95% confidence interval (CI) 7.09 to 9.86) in the benzylpenicillin and flucloxacillin combined group. In the flucloxacillin only group it was 8.71 doses (95% CI 6.90 to 10.5), a mean difference of -0.24 doses (95% CI -2.48 to 2.01, p = 0.83). Other markers of treatment efficacy showed no difference between groups at review the following day; temperature decrease (mean difference -0.07 degrees C, 95% CI -0.76 to 0.62, p = 0.84), or diameter decrease of affected area (mean difference -34 mm, 95% CI -99 to 31, p = 0.30). Patient subjective assessments were also similar between the different drug regimen; improvement on a visual analogue scale of pain/discomfort from admission to first review (mean difference 10 mm, 95% CI -12.6 to 14.2, p = 0.91) and on second review (mean difference 15 mm, 95% CI -18.6 to 21.6, p = 0.88). Patient overall subjective feelings of improvement on first review (p = 0.32) and on second review (p = 0.64) were also similar.\n This study provides no evidence to support the addition of intravenous benzylpenicillin to intravenous flucloxacillin in the treatment of lower limb cellulitis.", "The purpose of this study was to compare in a randomized, open-label clinical study, the efficacy and safety of cefepime (1 g every 12 hours) with that of ceftazidime (1 g every 8 hours) in patients with serious skin and skin-structure infections. Of 298 patients enrolled in the study, 130 with serious skin and skin-structure infections were evaluable. Demographics and underlying medical conditions were comparable in both groups. The most common infections were cellulitis, abscesses, ulcers, and postoperative wound infections. The most common pathogens isolated were Staphylococcus aureus, group A streptococci, Enterobacteriaceae, and Pseudomonas aeruginosa. Duration of therapy in the 93 patients treated with cefepime was 3-18 days and in the 37 ceftazidime-treated patients was 4-16 days. Pathogen bacteriologic response rates were high: 92% (124 of 135) of pathogens were eradicated by cefepime and 95% (55 of 58) by ceftazidime. Clinical response rates were satisfactory in 88% (82 of 93) of cefepime-treated patients and in 89% (33 of 37) of ceftazidime-treated patients. Adverse events occurred with similar frequency in both groups. Events probably related to study drugs affected 3% (6 of 198) of patients treated with cefepime and 4% (4 of 100) of ceftazidime-treated patients. Cefepime, a new parenteral cephalosporin administered every 12 hours, is an extremely well tolerated and effective alternative to ceftazidime given every 8 hours for the treatment of serious skin and skin-structure infections.", "Cellulitis is a condition routinely encountered in the primary care setting. No previous study has compared a short (5 days) vs standard (10 days) course of therapy of the same antibiotic in patients with uncomplicated cellulitis.\n We performed a randomized, double-blind, placebo-controlled trial to determine if 5 days of therapy has equal efficacy to 10 days of therapy for patients with cellulitis. Of 121 enrolled subjects evaluated after 5 days of therapy for cellulitis, 43 were randomized to receive 5 more days of levofloxacin therapy (10 days total antibiotic treatment), and 44 subjects to receive 5 more days of placebo therapy (5 days of total antibiotic treatment). Levofloxacin was given at a dose of 500 mg/d. Subjects were not randomized if they had worsening cellulitis, a persistent nidus of infection, a lack of any clinical improvement, or abscess formation within the first 5 days of therapy. The main outcome measure was resolution of cellulitis at 14 days, with absence of relapse by 28 days, after study enrollment.\n Eighty-seven subjects were randomized and analyzed by intention to treat. There was no significant difference in clinical outcome between the 2 courses of therapy (success in 42 [98%] of 43 subjects receiving 10 days of antibiotic, and 43 [98%] of 44 subjects receiving 5 days of antibiotic) at both 14 and 28 days of therapy.\n In patients with uncomplicated cellulitis, 5 days of therapy with levofloxacin appears to be as effective as 10 days of therapy.", "In this prospective, double-blind, multicentre trial, adult patients with complicated skin and skin structure infection (cSSSI) randomly received sequential intravenous (i.v.)/oral (p.o.) moxifloxacin (400 mg once a day) or a control regimen of i.v. piperacillin-tazobactam (3.0/0.375 g every 6 h) followed by p.o. amoxicillin-clavulanate (800 mg every 12 h), each for 7-14 days. Clinical cure rates at the test-of-cure visit (10-42 days post therapy) for the efficacy-valid population were 79% (143/180) for the moxifloxacin-treated group and 82% (153/187) for the control group (95% confidence interval, -12.04, 3.29). Bacteriological eradication rates for Staphylococcus aureus, the most prevalent organism, were 78% and 80%, respectively. The incidence of drug-related adverse events was similar for both groups (31% moxifloxacin, 30% control). Sequential i.v./p.o. moxifloxacin was as effective and well tolerated as i.v. piperacillin-tazobactam followed by p.o. amoxicillin-clavulanate in treating patients with cSSSI.", "Because of increasing resistance to older antimicrobial agents, newer drugs need to be evaluated for the treatment of skin and skin-structure infections (SSSIs). This double-masked, randomized, comparative, multicenter study enrolled patients aged 13 years or older with SSSIs to receive either cefdinir 300 mg BID or cephalexin 500 mg QID for 10 days. Nine hundred fifty-two patients (474 in the cefdinir group and 478 in the cephalexin group) took part, primarily white males between 18 and 65 years of age. There were two follow-up visits, with efficacy determined at the test-of-cure visit, 7 to 16 days posttherapy. Many patients were not microbiologically assessable, primarily because of negative cultures at study admission. Patients who required surgical intervention (e.g., incision and drainage) at the site of infection more than 24 hours after the initiation of drug therapy were defined as treatment failures. Significantly more isolated pathogens were resistant to cephalexin than to cefdinir. In the 178 efficacy-assessable cefdinir-treated patients, the rate of pathogen eradication was 93% (200/215), and the rate of successful clinical response was 88% (157/178), compared with 89% (221/247) and 87% (177/204), respectively, in the 204 efficacy-assessable cephalexin-treated patients. Using confidence-interval analysis, the microbiologic and clinical response rates of the cefdinir-treated patients were statistically equivalent to those of the cephalexin-treated patients. At the follow-up visits, patients were questioned about any adverse events occurring since their previous visit. Any untoward symptom occurring during or within 2 days after completion of drug treatment was considered an adverse reaction if the investigator judged it to be definitely, probably, or possibly related to the study drug. One hundred twenty-three (26%) cefdinir-treated patients and 77 (16%) cephalexin-treated patients experienced at least one adverse reaction, a statistically significant difference. Study drug was discontinued for adverse reactions in 20 (4%) cefdinir-treated patients and 13 (3%) cephalexin-treated patients; in the two groups, 10 and 7 patients, respectively, were discontinued for diarrhea. Cefdinir taken BID was as effective as cephalexin taken QID in the treatment of mild-to-moderate SSSIs and was well tolerated by most patients. The increased antibacterial activity of cefdinir must be balanced against the higher rate of diarrhea seen in patients treated with this drug.", "Uncomplicated skin and skin-structure infections are commonly observed in medical practice. Because these infections typically are confined to the superficial layers and seldom lead to the destruction of skin structures and resultant systemic dissemination, in general they can be treated with an oral antibiotic with potent microbiologic activity against gram-positive pathogens.\n This paper compares the efficacy and tolerability of 3 beta-lactam antibiotics in patients with uncomplicated skin and skin-structure infections.\n Two double-blind, multicenter, parallel-group studies were conducted, in which patients aged > or = 12 years with uncomplicated skin and skin-structure infections were randomized to receive cefditoren 200 or 400 mg, cefuroxime 250 mg, or cefadroxil 500 mg, each BID for 10 days. Study 1 compared cefditoren with cefuroxime; Study 2 compared cefditoren with cefadroxil. Clinical and microbiologic responses were assessed at a posttreatment visit (within 48 hours of treatment completion) and test-of-cure visit (7-14 days after treatment completion). Patients were monitored closely throughout the study with the use of physical examinations, clinical laboratory tests, and assessment of adverse events.\n A total of 1,685 patients (855 males, 830 females; mean age, 41.1 years [range, 12-95 years]) were enrolled. Within both studies, the 3 treatment groups were similar at baseline based on demographic characteristics and types of infection. Cellulitis (26%), wound infection (25%), and simple abscess (15%) were the most common infections. Clinical cure rates at the test-of-cure visit were 85% (443/523) for cefditoren 200 mg, 83% (427/516) for cefditoren 400 mg, 88% (234/265) for cefuroxime, and 85% (211/248) for cefadroxil. At the test-of-cure visit, cefditoren 200 mg had eradicated significantly fewer of the causative pathogens isolated before treatment in microbiologically evaluable patients than did cefuroxime in Study 1 (P = 0.043) but significantly more of the pathogens than did cefadroxil in Study 2 (P = 0.018). Eradication rates for the most commonly isolated pathogens were generally similar in the 3 treatment groups in both studies, with the only significant difference favoring cefditoren 200 and 400 mg over cefadroxil for Peptostreptococcus species in Study 2 (P = 0.016 and P = 0.003, respectively). A minority of patients (< or = 5% in any treatment group) discontinued study-drug treatment prematurely due to a treatment-related adverse event, with statistically higher rates for cefditoren 400 mg than for cefditoren 200 mg and the comparator cephalosporins (each P < 0.05). All 3 cephalosporins were generally well tolerated. Most adverse events (>93%) were categorized as mild to moderate, with the most common being diarrhea, nausea, and headache.\n In this population of patients with uncomplicated skin and skin-structure infections, including those due to Staphylococcus aureus or Streptococcus pyogenes, the clinical cure rate and tolerability of cefditoren were comparable to those of cefuroxime and cefadroxil.", "Meropenem, a broad-spectrum carbapenem with potent in vitro activity, is postulated to be an effective monotherapy for the treatment of complicated skin and skin structure infections (cSSSI).\n This multicenter, international, double-blind, randomized, prospective study of hospitalized patients with cSSSI evaluated the efficacy, safety, and tolerability of meropenem (500 mg IV q8h) versus imipenem-cilastatin (500 mg IV q8h). The primary efficacy endpoint was clinical outcome at follow-up in the clinically evaluable (CE) and modified intent-to-treat populations (MITT; patients who met eligibility criteria and received at least one dose of study drug). The study aimed to demonstrate non-inferiority (delta of 10%, 95% confidence intervals) in clinical response in the CE population. Clinical responses for all pathogens at follow-up were assessed in the fully evaluable population (CE population with baseline pathogen and follow-up cultures).\n In total, 1,076 patients were enrolled. Of these, 692 patients comprised the MITT population (334 and 358 patients randomized to meropenem and imipenem-cilastatin, respectively) and 548 the CE population (261 and 287 patients randomized to meropenem and imipenem-cilastatin, respectively). Cure rates were 86.2% (meropenem) and 82.9% (imipenemcilastatin; 95% CI, -2.8, 9.3) in the CE population and 73.1% (meropenem) and 74.9% (imipenem-cilastatin; 95% CI, -8.4, 4.7) in the MITT population. The frequencies of adverse events and drug-related adverse events were similar between treatment groups.\n In one of the largest studies conducted to date of hospitalized patients with cSSSI, meropenem, 500 mg IV q8h had comparable safety and efficacy to imipenem-cilastatin, 500 mg IV q8h." ]

[ "16020142", "12851127", "6512869", "242302", "12010236", "2246790" ]

[ "Psychogenic erectile dysfunction: comparative study of three therapeutic approaches.", "The potential benefit of vacuum devices augmenting psychosexual therapy for erectile dysfunction: a randomized controlled trial.", "Rational-emotive therapy in the treatment of erectile failure: an initial study.", "Systematic desensitization of erectile impotence: a controlled study.", "Intracavernosal injection therapy with and without sexological counselling in men with erectile dysfunction.", "Educational intervention as an adjunct to treatment of erectile dysfunction in older couples." ]

[ "We administered the International Index of Erectile Function (IIEF; Rosen et al., 1997) questionnaire to 30 patients with psychogenic erectile dysfunction (ED) at baseline, immediately after treatment, and 3 months after treatment. We randomized patients into three groups: group I, who had weekly sessions of time-limited theme-based group psychotherapy for 6 months and 50 mg sildenafil citrate orally on demand; group II, who had an intake of 50 mg sildenafil citrate orally on demand for 6 months only; and group III, who had weekly sessions of time-limited theme-based group psychotherapy for 6 months. We analyzed data (15-item IIEF) for each group at three times during the study and compared by the data using analysis of variance (ANOVA), followed by the Bonferroni multiple comparison test. We used Cochran's Q-test for analysis between baseline and posttreatment stages of patients with remission of symptoms (EF equal to or higher than 26 points). Group III had a mean score higher than group II, with the difference being statistically significant (immediately after treatment, p = 0.033; at 3 months after treatment, p = 0.049; p < 0.05). All three therapeutic alternatives resulted in an improvement of erectile function domain score. However, significant differences from baseline were observed in groups I (p = 0.0009) and III (p = 0.0002) but not in group II (p = 0.135). The psychotherapy groups, I and III, had significantly higher scores compared with group II, in which patients were exclusively treated with sildenafil citrate. These findings suggest that time-limited theme-based group psychotherapy is an effective treatment for psychogenic ED.", "A cohort of 45 patients diagnosed with predominant psychogenic erectile disorder (ED) chose couples psychotherapy. We randomized 25 couples to also receive a vacuum constriction device (VCD), also known as a vacuum erectile device, at the second session (group 1), whereas 20 couples had psychotherapy without a VCD. Twenty-one couples (84%) in group 1 reported some improvement after the initial psychotherapy and VCD sessions compared with 12 of the 20 couples (60%) who reported some improvement after couples psychotherapy in group 2. We subsequently found that 3 of the 4 couples in group 1 reporting no improvement had not used the pump provided. Early combination treatment of couples psychotherapy and a physical treatment such as a VCD may lead to a greater beneficial response in men with ED than therapy alone. The delay of demonstrating the capacity and potential benefit from a physical intervention may have a marked effect on the initial and ongoing response to sex therapy.", "Sixteen males with erectile failure, married or living with their partners, were assigned to either 12 bi-weekly sessions (6 weeks) of Rational Emotive Therapy (RET) or a 6-week waiting-list control group. Active treatment administered by a graduate student in psychology with special training in RET resulted in patients making significantly more sexual intercourse attempts, reporting significantly reduced sexual anxiety, and having a significantly higher number of successful intercourse attempts than the waiting-list control group. While 6-9 month follow-up revealed that most treated patients had fallen back toward the pretest baseline (lower rates of successful intercourse), group means as a whole were still significantly higher than pretreatment intercourse success rates. The significance of these findings are discussed.", "Results of a study conducted to assess the therapeutic effectiveness of systematic desensitization of erectile impotence are described. Three groups of eight patients each were formed. They were treated with systematic desensitization or conventional medication and general advice, or put on a waiting list. Therapeutic effects were investigated on the behavioral, subjective, and physiological levels. There were no significant differences among the three groups except on the subjective level. On this level, after therapy the systematic desensitization group rated feelings in sexually arousing situations as associated with significantly less anxiety than the other two groups. Systematic desensitization used alone as a treatment for erectile impotence shows only limited therapeutic effect. The unimproved patients were later treated using a modification of the Masters and Johnson technique. Early results suggest that this technique may be superior to systematic desensitization alone.", "To compare the acceptance of and satisfaction with intracavernosal injection (ICI) therapy with and without sexological counselling in men with erectile dysfunction (ED).\n In a prospective randomized study, men were alternately assigned to ICI without sexological counselling (-SC) or with sexological counselling (+SC). In all, 70 patients were included, i.e. 35 in each group; 57 (28 -SC, 29 +SC) were interviewed by telephone after a mean follow-up of 11.3 months to determine their use of ICI and reasons for discontinuing.\n There were no differences between the groups in discontinuation of ICI (overall 30%), in reasons for discontinuing ICI (24% did so because of the return of spontaneous erections) or in sexual functioning.\n There was no positive contribution from additional sexological counselling but extensive information and support by the urologist seems to be sufficient, resulting in a high acceptance rate of ICI. The discontinuation rate (30%) is one of the lowest reported.", "This study examined the effects of a sex and aging workshop highlighting permission and limited information on the sexual knowledge, attitudes, behaviors, and satisfaction of a group of older heterosexual couples experiencing erectile dysfunction. The workshop focused on disseminating information about the physiological and psychological changes that occur in the sexual response during the aging process. Twenty couples participated in this study: 10 attended a workshop and 10 served as controls. The study utilized a randomized control group pretest/posttest design. Workshop participants completed an evaluation form and were interviewed at the time of follow-up. Data analysis revealed that the workshop participants reported significant increases in knowledge levels and in sexual satisfaction. The workshop evaluations and follow-up interviews reinforced these quantitative results. This study lends support to educational intervention as an adjunct to treatment of erectile dysfunction in the elderly population." ]

[ "10081532", "15649161", "8484499", "18043058", "12477673", "3092933", "9069860", "16895618", "10823097", "14725517", "12411789", "1544195", "9924226", "15321185", "15385352", "12151925", "8488993", "12067865", "14608559", "10764175", "11226090", "15872126", "1859764", "14973803", "7892973", "2181138", "12705488", "8721471", "10319779", "8447210", "2140030", "10434821", "11818760", "18679598", "2605083", "16428565" ]

[ "Effect and placebo effect of acupressure (P6) on nausea and vomiting after outpatient gynaecological surgery.", "Comparison of laser acupuncture and metoclopramide in PONV prevention in children.", "Transcutaneous electrical nerve stimulation reduces the incidence of vomiting after hysterectomy.", "Monitoring of neuromuscular blockade at the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting.", "P6 acupressure may relieve nausea and vomiting after gynecological surgery: an effectiveness study in 410 women.", "Traditional Chinese acupuncture: a potentially useful antiemetic?", "Nonpharmacologic treatment of postoperative nausea.", "Acupressure for postoperative nausea and vomiting in gynaecological patients receiving patient-controlled analgesia.", "Acupressure and prevention of nausea and vomiting during and after spinal anaesthesia for caesarean section.", "Acupuncture compared to placebo-acupuncture for postoperative nausea and vomiting prophylaxis: a randomised placebo-controlled patient and observer blind trial.", "Comparative efficacy of acustimulation (ReliefBand) versus ondansetron (Zofran) in combination with droperidol for preventing nausea and vomiting.", "Ineffectiveness of acupuncture and droperidol in preventing vomiting following strabismus repair in children.", "Laser stimulation of acupuncture point P6 reduces postoperative vomiting in children undergoing strabismus surgery.", "Acupressure for intrathecal narcotic-induced nausea and vomiting after caesarean section.", "A randomized controlled comparison of electro-acupoint stimulation or ondansetron versus placebo for the prevention of postoperative nausea and vomiting.", "P6 acupoint injections are as effective as droperidol in controlling early postoperative nausea and vomiting in children.", "[Acupressure in the prevention of postoperative nausea and vomiting].", "Acupressure and ondansetron for postoperative nausea and vomiting after laparoscopic cholecystectomy.", "Comparison of acupressure bands and droperidol for reducing post-operative nausea and vomiting in gynecologic surgery patients.", "Acupressure wristbands do not prevent postoperative nausea and vomiting after urological endoscopic surgery.", "The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery.", "Prevention of PONV by acustimulation with capsicum plaster is comparable to ondansetron after middle ear surgery.", "Effect of P6 acupressure on postoperative vomiting in children undergoing outpatient strabismus correction.", "Acupressure wristbands for the prevention of postoperative nausea and vomiting in adults undergoing cardiac surgery.", "P6 acupressure and nausea and vomiting after gynaecological surgery.", "Postoperative nausea is relieved by acupressure.", "Effect of acupressure on postoperative nausea and vomiting in laparoscopic cholecystectomy.", "Effect of P-6 acupressure on prevention of nausea and vomiting after epidural morphine for post-cesarean section pain relief.", "Acupressure-acupuncture antiemetic prophylaxis in children undergoing tonsillectomy.", "Comparison of P6 acupoint injection with 50% glucose in water and intravenous droperidol for prevention of vomiting after gynecological laparoscopy.", "Electro-acupuncture and postoperative emesis.", "Acupressure and the prevention of nausea and vomiting after laparoscopy.", "Electroacupuncture prophylaxis of postoperative nausea and vomiting following pediatric tonsillectomy with or without adenoidectomy.", "Evaluation of transcutaneous electroacupoint stimulation with the train-of-four mode for preventing nausea and vomiting after laparoscopic cholecystectomy.", "Effect of stimulation of the P6 antiemetic point on postoperative nausea and vomiting.", "Transcutaneous acupoint electrical stimulation with the ReliefBand for the prevention of nausea and vomiting during and after cesarean delivery under spinal anesthesia." ]

[ "Acupuncture and acupressure have previously been reported to possess antiemetic effect. We wanted to investigate the \"true\" and placebo effect of acupressure in prevention of postoperative nausea and vomiting (PONV).\n Sixty women undergoing outpatient minor gynaecological surgery were entered into a double-blind and randomised study. One group received acupressure with bilateral stimulation of P6 (A), a second group received bilateral placebo stimulation (P) and a third group received no acupressure wrist band and served as a reference group (R). PONV was evaluated as number of patients with complete response (no PONV), nausea only or vomiting. In addition, the need for rescue antiemetic medication and nausea after 24 h was registered.\n Complete response was obtained in 11, 11 and 9 patients in groups, A, P and R, respectively. Nine, 7 and 6 patients had nausea before discharge home, and 1, 1 and 8 patients were nauseated (8 vs 1 patient: P < 0.05) 24 h after operation in A, P and R groups, respectively. When compared to placebo acupressure (2 patients vomited and 5 needed rescue), significantly (P < 0.05) fewer needed rescue antiemetic medication after acupressure at P6 (no vomiting or rescue medication). When compared to the observation group (5 vomited and 4 needed rescue antiemetics), significantly fewer vomited after acupressure (P < 0.05)\n In patients undergoing brief gynaecological surgery, placebo effect of acupressure decreased nausea after 24 h but vomiting and need of rescue antiemetics was reduced only by acupressure with the correct P6 point stimulation.", "Postoperative nausea and vomiting (PONV) are frequent side effects of general anesthesia in children. The aim of this study was to compare the effectiveness of laser acupuncture with metoclopramide in prevention of PONV in children after sevoflurane anesthesia.\n A total of 120 children ASA I and II, scheduled for hernia repair, circumcision or orchidopexy were randomly assigned into three groups: group I, received laser acupuncture on P6 point and saline infusion; group II, metoclopramide 0.1 mg.kg(-1) i.v. and sham laser; group III had sham laser and saline infusion. Anesthesia was maintained with sevoflurane and N(2)O/O(2). Patients were monitored for any symptoms of retching and vomiting at 2, 6 and 24 h postoperatively.\n The incidence of vomiting was higher in the control group in the first 2 h postoperatively (P < 0.001), compared with the other groups. There was no statistically significant difference between acupuncture and metoclopramide groups in occurrence and timing of vomiting (P < 0.001).\n Laser acupuncture is equally effective as metoclopramide in preventing PONV in children.", "The possible postoperative antiemetic effect of transcutaneous electrical nerve stimulation (TENS) on the P6 point (on the Pericardium Channel of Hand-Jueyin) was evaluated in 103 women undergoing hysterectomy. TENS on the P6 point was applied 30-45 min before induction of anesthesia in 51 patients and continued for 6 h postoperatively. The control group, 52 patients, was treated exactly in the same way but with the electrical stimulator turned off. Incidence of vomiting was assessed blindly 2 h, 4 h, 6 h, and 8 h postoperatively. The incidence of vomiting postoperatively was significantly less in the TENS-treated group when compared with the control group (between 0 h and 2 h: 23% vs 43%, P < 0.05; between 2 h and 4 h: 27% vs 50%, P < 0.025; and between 4 h and 6 h: 31% vs 67%, P < 0.001, respectively). Six hours postoperatively TENS was discontinued, and 8 h postoperatively the two groups did not differ significantly for incidence of vomiting (between 6 h and 8 h: 51% vs 65%). The authors conclude that TENS reduces the incidence of vomiting after hysterectomy.", "Electrical stimulation of the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting (PONV). Neuromuscular blockade during general anesthesia can be monitored with electrical peripheral nerve stimulation at the wrist. The authors tested the effect of neuromuscular monitoring over the P6 acupuncture point on the reduction of PONV.\n In this prospective, double-blinded, randomized control trial, the authors investigated, with institutional review board approval and informed consent, 220 women undergoing elective laparoscopic surgery anesthetized with fentanyl, sevoflurane, and rocuronium. During anesthesia, neuromuscular blockade was monitored by a conventional nerve stimulator at a frequency of 1 Hz over the ulnar nerve (n = 110, control group) or over the median nerve (n = 110, P6 group) stimulating at the P6 acupuncture point at the same time. The authors evaluated the incidence of nausea and vomiting during the first 24 h.\n No differences in demographic and morphometric data were found between both groups. The 24-h incidence of PONV was 45% in the P6 acupuncture group versus 61% in the control group (P = 0.022). Nausea decreased from 56% in the control group to 40% in the P6 group (P = 0.022), but emesis decreased only from 28% to 23% (P = 0.439). Nausea decreased substantially during the first 6 h of the observation period (P = 0.009). Fewer subjects in the acupuncture group required ondansetron as rescue therapy (27% vs. 39%; P = 0.086).\n Intraoperative P6 acupuncture point stimulation with a conventional nerve stimulator during surgery significantly reduced the incidence of PONV over 24 h. The efficacy of P6 stimulation is similar to that of commonly used antiemetic drugs in the prevention of PONV.", "To investigate the effect of sensory stimulation of the P6 point on postoperative nausea and vomiting (PONV) after gynecological surgery in the everyday clinical setting (effectiveness study).\n Four hundred and ten women undergoing general anesthesia for elective gynecological surgery were included in a prospective, consecutive, randomized, multicentre, placebo-controlled, double-blind clinical trial with a reference group. One group was given bilateral P6 acupressure (n = 135), a second group similar pressure on bilateral non-acupressure points (n = 139), and a third group (n = 136) served as reference group. Nausea (scale 0-6), vomiting, pain, and satisfaction with the treatment were recorded. Primary outcome was complete response, i.e., no nausea, vomiting or rescue medication for 24 hr. Results were analyzed by applying logistic regression with indicators of treatments, type of operation and risk score for PONV as explanatory variables.\n Complete response was more frequent in the P6 acupressure group than in the reference group (P = 0.0194) Conversely, the incidence of PONV was 46% in the reference group, 38% after pressure on a non-acupoint and 33% after P6 acupressure. The decrease from 46% to 33% was statistically significant. When considering vaginal cases separately, the decrease in PONV was from 36% to 20% (P = 0.0168). The corresponding decrease from 59% to 55% in the laparoscopic surgery group was not statistically significant.\n P6 acupressure is a non-invasive method that may have a place as prophylactic antiemetic therapy during gynecological surgery.", "Two consecutive studies were undertaken to evaluate the effectiveness of acupuncture as an antiemetic used in addition to premedication with opioids in patients undergoing minor gynaecological operations. In the first study 25 of the 50 patients underwent acupuncture immediately after premedication with 100 mg meptazinol, the rest receiving the drug alone, and in the second 75 patients were allocated randomly to one of three groups: a group receiving 10 mg nalbuphine and acupuncture, a group receiving premedication and dummy acupuncture, and a group receiving premedication alone. Manual needling for five minutes at the P6 acupuncture point (Neiguan) resulted in a significant reduction in perioperative nausea and vomiting in the 50 patients who underwent acupuncture compared with the 75 patients who received no acupuncture. These findings cannot be explained, but it is recommended that the use of acupuncture as an antiemetic should be explored further.", "Nausea is the most common postoperative complication of anesthesia. Appropriately applied acupressure offers a safe and cost-effective nursing approach to the prevention of this problem. This study tested the effect of acupressure on the incidence of postoperative nausea in same-day surgery patients.\n Ninety outpatient surgery patients were randomly assigned to one of three groups. The treatment group (n = 30) received bilateral elastic bands designed to exert pressure on the appropriate location on the distal aspect of the wrist during the perioperative period. The placebo group (n = 30) had elastic bands incapable of acupressure placed on their wrists. The control group (n = 30) received routine nursing and medical interventions for nausea and vomiting. Antiemetics were prescribed by the anesthesiologist and administered to patients in all three groups if nausea persisted and/or emesis occurred. The incidences of nausea or vomiting were tabulated separately for operating room, PACU phase I, and PACU phase II, and compared using Fisher's Exact Test.\n The incidence of nausea and vomiting did not differ overall in the OR or PACU phase I. However, in PACU phase II the incidence was 10% in the treatment group, 20% in the placebo group, and 50% in the control group (overall, P = .0001). Treatment wrist bands reduced the incidence of nausea and vomiting as compared with the control group (P = .0001), as did the placebo wrist bands (P = .0033). The numerical trend suggests that the incidence is reduced by half. The incidence of nausea can be significantly reduced by the use of placebo and suggests that further reduction can be obtained by using acupressure.", "To evaluate the effectiveness of acupressure in preventing nausea and vomiting in patients undergoing gynaecological operations and receiving a patient-controlled analgesia device.\n Patients aged between 40 and 65 yr were included. Exclusion criteria were obesity, diabetes mellitus, and history of motion sickness, postoperative nausea and vomiting, or smoking. Patients were randomized into one of two groups, acupressure and control. In the acupressure group, acupressure bands were placed on both wrists with the plastic bead positioned at the P6 point. In controls, beads were placed at a non-acupoint site. All patients received a standard general anaesthetic. Postoperatively, patients were connected to a patient-controlled analgesia device with morphine (loading dose 5 mg, background infusion 1 mg h-1, bolus dose 1 mg and lock-out time 10 min). Pain and sedation scores, respiratory rate, heart rate, arterial pressure and oxygen saturation were recorded for 24 h. Metoclopramide 10 mg was administered intravenously as a rescue antiemetic.\n Fifty patients received acupressure and 50 were controls. In the acupressure group, 33% of patients had nausea compared with 63% controls. The cumulative incidence of vomiting at 24 h was 25% with acupressure and 61% in controls. The incidence of nausea, vomiting and antiemetic use was significantly lower with acupressure.\n Acupressure at the P6 meridian point is an effective alternative for the prevention of nausea and vomiting in patients receiving patient-controlled analgesia with morphine after gynaecological surgery.", "The efficacy of acupressure at the P6 point in the prevention of nausea and vomiting during and after Caesarean section was studied. A double-blind, randomized controlled study of acupressure vs placebo was designed. Ninety-four patients scheduled for Caesarean section were included. The anaesthetic technique and postoperative analgesia were standardized. The use of acupressure reduced the incidence of nausea or vomiting from 53% to 23% compared with placebo (95% confidence interval (CI) 0.34-0.25; P = 0.002) during the operation and from 66% to 36% compared with placebo (95% CI 0.34-0.19; P = 0.003) after the operation. Other variables were similar between the groups.", "This randomised, placebo-controlled, patient and observer blinded trial was conducted to determine whether acupuncture at the acupuncture point P6 is effective in preventing postoperative nausea and vomiting (PONV) compared to placebo acupuncture. Female patients (n = 220) scheduled for gynaecological or breast surgery were randomly assigned to two groups receiving either acupuncture (n = 109) or placebo acupuncture (n = 111). Each group was stratified for type of surgery and included two subgroups receiving intervention either before or after induction of anaesthesia. The incidence of PONV and/or antiemetic rescue medication within 24 h after surgery was the main outcome measure which showed no statistically significant difference between groups (43.7% acupuncture, 50.9% placebo, p = 0.27). The differences were more pronounced for patients having gynaecological surgery (48.9% acupuncture, 67.6% placebo, p = 0.07) than for those having breast surgery (38.7% acupuncture, 40.3% placebo, p = 0.86). The secondary outcome, vomiting, was significantly reduced by acupuncture from 39.6% to 24.8% (p = 0.03). Subgroup analysis showed no difference between applications of acupuncture before compared to after induction of anaesthesia.", "Antiemetic drugs are costly, are associated with variable efficacy, and can produce unwanted side effects when used for prophylaxis against postoperative nausea and vomiting. This clinical study was designed to compare the efficacy of transcutaneous electrical acupoint stimulation using a ReliefBand to ondansetron (Zofran) when utilized alone or in combination for preventing postoperative nausea and vomiting after plastic surgery.\n A single-center, randomized, double-blind, placebo- and sham-controlled study design was conducted to compare three prophylactic antiemetic treatment regimens in 120 outpatients undergoing plastic surgery procedures with routine low-dose droperidol prophylaxis: (1) ondansetron (n = 40), 4 mg intravenous ondansetron and a sham ReliefBand; (2) acustimulation (n = 40), 2 ml intravenous saline and an active ReliefBand; and (3) combination (n = 40), 4 mg intravenous ondansetron and an active ReliefBand. The incidences of postoperative nausea and vomiting, as well as the need for \"rescue\" antiemetics, were determined at specific time intervals for up to 72 h after surgery. The outcome variables assessed included recovery times, quality of recovery score, time to resumption of normal diet, and patient satisfaction with the prophylactic antiemetic therapy.\n Use of the ReliefBand in combination with ondansetron significantly reduced nausea (20 vs. 50%), vomiting (0 vs. 20%), and the need for rescue antiemetics (10 vs. 37%) compared with ondansetron alone at 24 h after surgery. Furthermore, the ability to resume a normal diet (74 vs. 35%) within 24 h after surgery was significantly improved when the ReliefBand was used to supplement ondansetron (vs. ondansetron alone). Finally, the quality of recovery (90 +/- 10 vs.70 +/- 20) and patient satisfaction (94 +/- 10 vs. 75 +/- 22) scores were significantly higher in the combination group the ondansetron group. There were no significant differences between the ReliefBand and ondansetron when administered as adjuvants to droperidol for antiemetic prophylaxis.\n The ReliefBand compared favorably to ondansetron (4 mg intravenously) when used for prophylaxis against postoperative nausea and vomiting. Furthermore, the acustimulation device enhanced the antiemetic efficacy of ondansetron after plastic surgery.", "The antiemetic effects and side-effects of P6 acupuncture and droperidol pre-treatment were evaluated in a randomized, patient- and observer-blinded study. Ninety unpremedicated children of ASA physical status I or II undergoing outpatient strabismus repair, and aged over one year, were studied. All patients received intravenous thiopentone 5 mg.kg-1, atropine 0.02 mg.kg-1 and succinylcholine 1.5 mg.kg-1, and the trachea was intubated. Patients then received either intravenous droperidol 0.075 mg.kg-1, droperidol plus five minutes' P6 acupuncture, or acupuncture alone. Anaesthesia was maintained with nitrous oxide 66% and halothane 1.5-2.0% in oxygen with spontaneous ventilation. There was no difference in the incidence of vomiting in the droperidol group (17% before discharge from hospital and 41% up to 48 hours after discharge), combined treatment group (17% and 34% respectively) and acupuncture group (27% and 45% respectively). Corresponding figures for the incidence of vomiting before discharge were 17%, 17% and 27% respectively; these values were also not different. The incidence of restlessness was significantly greater in children receiving droperidol (63%) or both treatments (67%) than in those receiving acupuncture alone (30%; P = 0.007). P6 acupuncture and droperidol are equally ineffective in preventing vomiting within 48 hours of paediatric strabismus repair. Droperidol is associated with increased incidence of postoperative restlessness.", "We conducted a double-blind, randomized, placebo-controlled study to investigate the effectiveness of P6 acupuncture on postoperative vomiting in children undergoing strabismus surgery. Acupuncture was performed by laser stimulation with a low-level laser. Laser stimulation of P6 was administered 15 min before induction of anaesthesia and 15 min after arriving in the recovery room. In the laser stimulation group, the incidence of vomiting was significantly lower (25%) than that in the placebo group (85%).", "In this randomized double-blind trial we investigated the effect of acupressure on the incidence of nausea and vomiting after caesarean section under spinal anaesthesia with added intrathecal morphine. Parturients wore either acupressure or placebo wristbands during surgery and postoperatively for at least 10 h. There was no significant difference overall between the two groups in the incidence of intra- or postoperative nausea or vomiting/retching. Demand for antiemetic medication was also similar in the two groups. However, in the sub-group of parturients who gave a previous history of postoperative nausea or vomiting, there was a statistically significant reduction in both postoperative nausea and vomiting/retching in the acupressure group. Further investigations are needed to see whether acupressure may be an effective non-pharmacological, non-invasive treatment for a common problem in this sub-group of patients.", "In this study we evaluated the efficacy of electro-acupoint stimulation, ondansetron versus placebo for the prevention of postoperative nausea and vomiting (PONV). Patients undergoing major breast surgery under general anesthesia were randomized into active electro-acupoint stimulation (A), ondansetron 4 mg IV (O), or sham control (placement of electrodes without electro-acupoint stimulation; placebo [P]). The anesthetic regimen was standardized. The incidence of nausea, vomiting, rescue antiemetic use, pain, and patient satisfaction with management of PONV were assessed at 0, 30, 60, 90, 120 min, and at 24 h. The complete response (no nausea, vomiting, or use of rescue antiemetic) was significantly more frequent in the active treatment groups compared with placebo both at 2 h (A/O/P = 77%/64%/42%, respectively; P = 0.01) and 24 h postoperatively (A/O/P = 73%/52%/38%, respectively; P = 0.006). The need for rescue antiemetic was less in the treatment groups (A/O/P = 19%/28%/54%; P = 0.04). Specifically, the incidence and severity of nausea were significantly less in the A group compared with the other groups, and in the O group compared with the P group (A/O/P = 19%/40%/79%, respectively). The A group experienced less pain in the postanesthesia care unit, compared with the O and P groups. Patients in the treatment groups were more satisfied with their management of PONV compared with placebo. When used for the prevention of PONV, electro-acupoint stimulation or ondansetron was more effective than placebo with greater degree of patient satisfaction, but electro-acupoint stimulation seems to be more effective in controlling nausea, compared with ondansetron. Stimulation at P6 also has analgesic effects.", "P6 acupuncture in adults is reported to be an effective preventive treatment for postoperative nausea and vomiting (PONV). It is not clear, however, whether this technique is effective as a preventive treatment for PONV in children.\n Children undergoing anesthesia and surgery were randomized to four groups: (a) intravenous saline + bilateral P6 acupoint injections (n = 50); (b) intravenous droperidol + bilateral P6 sham acupuncture (n = 49); (c) intravenous saline + bilateral sham point injections (n = 43); (d) intravenous saline +bilateral P6 sham acupuncture (n = 45). The perioperative anesthetic technique was standardized in all subjects. The incidence of postoperative nausea and vomiting (PONV) was evaluated in postanesthesia care unit (PACU) and 24 h after surgery.\n Incidence of nausea in the PACU was significantly lower in the acupoint group as compared with the sham point group (32% vs. 56%, P = 0.029) and P6 sham group (32% vs. 64%, P = 0.002) but not as compared with the droperidol group (32% vs. 46%, P = ns). Similarly, subjects in the acupoint group had a significantly lower incidence of vomiting in the PACU as compared with the sham point group (12% vs. 33%, P = 0.026) and P6 sham group (12% vs. 31%, P = 0.029) but not as compared with the droperidol group (12% vs. 18%, P = ns). The combined incidence of early PONV was also lower in the acupoint group as compared with the sham point group (P = 0.045) and P6 sham group (P = 0.004) but not as compared with the droperidol group (42% vs. 51%, P = ns). Finally, significantly fewer subjects in the acupoint group required intravenous ondansetron as an initial rescue therapy (P = 0.024). At 24 h after surgery, however, the incidence of late PONV was similar among the four study groups (P = ns).\n In children, P6 acupoint injections are as effective as droperidol in controlling early postoperative nausea and vomiting.", "Despite modern anaesthetic procedures, postoperative nausea and vomiting are still the side-effects most often mentioned: acupressure is reported to be an additional method of preventing these effects in minor gynaecological surgery. We investigated the effectiveness of acupressure in patients undergoing gynaecological operations of longer duration (6-8 h) in a verum acupressure group compared to a placebo group. Before beginning the study we investigated a control group to find out the frequency of emesis. In the worst case of nausea that we encountered, 80% in the 0-6 h postoperative period, the number of random samples for the acupressure and placebo groups was calculated (30 patients in each group). The error for alpha was established at 5% and the reduction of nausea was 50%. METHODS. The female patients were 18 to 65 years old (ASA group I and II). Acupressure was carried out by fastening small metal bullets at the point P 6 to each forearm by means of an elastic bandage. The bullets were left there for 24 h. The premedication anaesthesia, postoperative analgesia, and antiemetic treatment were standardized. During a 24-h period we investigated the incidence of nausea and vomiting. RESULTS. The anthropometric data, the duration of surgery and the amount of postoperative analgesia were comparable between the three groups. Verum acupressure obtained a statistically significant and relevant reduction in nausea up to the 6th postoperative hour in comparison with the placebo group (P = 0.03). Nausea was reduced from 53% in the placebo group to 23% in the acupressure group. CONCLUSION. As demonstrated in this group of longer gynaecological surgery patients as well as in chemotherapy-induced nausea and vomiting, we were able to demonstrate that acupressure is an effective method of preventing nausea and vomiting without any side-effects. It is a valuable addition to the prevention of postoperative nausea and vomiting. Further studies should be conducted to investigate this possibility further.", "To compare the efficacy of acupressure wrist bands and ondansetron for the prevention of postoperative nausea and vomiting (PONV).\n One hundred and fifty ASA I-II, patients undergoing elective laparoscopic cholecystectomy were included in a randomized, prospective, double-blind and placebo-controlled study. Patients were divided into three groups of 50. Group I was the control; Group II received ondansetron 4 mg iv just prior to induction of anesthesia; in Group III acupressure wristbands were applied at the P6 points. Acupressure wrist bands were placed inappropriately in Groups I and II. The acupressure wrist bands were applied 30 min prior to induction of anesthesia and removed six hours following surgery. Anesthesia was standardized. PONV were evaluated separately as none, mild, moderate or severe within six hours of patients' arrival in the postanesthesia care unit and then at 24 hr after surgery by a blinded observer. If patients vomited more than once, they were given 4 mg ondansetron iv as the rescue antiemetic. Results were analyzed by Z test. A P value of < 0.05 was taken as significant.\n The incidence of PONV and the requirement of rescue medication were significantly lower in both the acupressure and ondansetron groups during the first six hours.\n Acupressure at P6 causes a significant reduction in the incidence of PONV and the requirement for rescue medication in the first six hours following laparoscopic cholecystectomy, similar to that of ondansetron 4 mg iv.", "The purpose of this study was to evaluate the effectiveness of acupressure bands, droperidol, and the combined modalities, administered preoperatively, in reducing PONV in inpatient gynecologic patients. One hundred and forty-three patients were randomized to one of four groups: droperidol and acupressure bands, droperidol and placebo bands, placebo drug and acupressure bands, or placebo drug and placebo bands. Overall, during their hospital stay, 69% of the women experienced PONV and 45% experienced vomiting at some time. Although droperidol was most effective the day of surgery, neither acupressure bands or droperidol were effective in reducing PONV.", "To evaluate the efficacy of acupressure wristbands in the prevention of postoperative nausea and vomiting (PONV).\n Two hundred ASA I-II patients undergoing elective endoscopic urological procedures were included in a randomized, prospective, double blind, placebo-controlled study. Spherical beads of acupressure wristbands were placed at the P6 points in the anterior surface of both forearms in Group I patients (acupressure group, n = 100) whereas, in Group 2 (control group, n = 100) they were placed inappropriately on the posterior surface. The acupressure wristbands were applied 30 min before induction of anesthesia and were removed six hours postoperatively. Anesthesia was induced with thiopental and maintained with nitrous oxide and oxygen, fentanyl, isoflurane and vecuronium. The tracheas were extubated on the operation table after patients received neostigmine and atropine. Post operative nausea and vomiting were evaluated separately as none, mild, moderate or severe at the time of patient's arrival in PACU, then at six hours and twenty-four hours after surgery by a blinded observer.\n In the acupressure group, 25 patients had PONV compared with 29 patients in the control group (P = NS).\n Application of acupressure wristbands at the P6 of both forearms 30 min before induction of anesthesia did not decrease the incidence of PONV in patients undergoing endoscopic urological procedures.", "Nonpharmacologic techniques may be effective in preventing postoperative nausea and vomiting (PONV). This sham-controlled, double-blinded study was designed to examine the antiemetic efficacy of transcutaneous acupoint electrical stimulation (TAES) in a surgical population at high risk of developing PONV. We studied 221 outpatients undergoing laparoscopic cholecystectomy with a standardized general anesthetic technique in this randomized, multicenter trial. In the TAES group, an active ReliefBand(Woodside Biomedical, Inc., Carlsbad, CA) device was placed at the P6 acupoint, whereas in the Sham and Placebo groups, an inactive device was applied at the P6 acupoint and at the dorsal aspect of the wrist, respectively. The ReliefBand was applied after completion of electrocautery and remained in place for 9 h after surgery. The incidence of PONV and need for \"rescue\" medication were evaluated at predetermined time intervals. TAES was associated with a significantly decreased incidence of moderate-to-severe nausea as denoted on the Functional Living Index-Emesis score for up to 9 h after surgery (5%-11% for the TAES group vs 16%-38% [P < 0.05] and 15%-26% [P < 0.05] for Sham and Placebo groups, respectively). TAES was also associated with a larger proportion of patients free from moderate to severe nausea symptoms (73% vs 41% and 49% for Sham and Placebo groups, respectively; P < 0.05). However, there were no statistically significant differences among the three groups with regard to incidence of vomiting or the need for rescue antiemetic drugs. We conclude that TAES with the ReliefBand at the P6 acupoint reduces nausea, but not vomiting, after laparoscopic cholecystectomy.\n Transcutaneous acupoint electrical stimulation at the P6 acupoint reduced postoperative nausea, but not vomiting, in outpatients undergoing laparoscopic cholecystectomy procedures.", "To compare the efficacy of stimulation of P6 acupoint with capsicum plaster in comparison with iv ondansetron for the prevention of postoperative nausea and vomiting (PONV).\n 120 patients of either sex, ASA I-II, undergoing elective middle ear surgeries under general anesthesia were included in this randomized, prospective, double-blinded and placebo-controlled study. The anesthetic technique was standardized. Patients were divided into three groups. Group I was the control group. Capsicum plaster (1 x 1 cm) was affixed at the P6 acupoint on both forearms 30 min before induction of anesthesia in patients of Group II. Patients of Groups I and III received an inactive adhesive plaster at the same site. Ondansetron 4 mg iv was given to patients of Group III at the end of surgery and the rest of the patients received a placebo. The plasters were removed six hours after transferring the patients to the postoperative unit. Criteria were fixed for the administration of rescue antiemetics (ondansetron 4 mg iv). PONV and the requirement for rescue antiemetics were recorded by a blinded observer.\n The incidence of PONV and the requirement for rescue antiemetics were significantly lower in both the acustimulation and ondansetron groups at six hours. At 24 hr there was a reduction in the requirement for rescue medication in the ondansetron group.\n Stimulation of the P6 acupoint with capsicum plaster is an effective method for prevention of PONV after middle ear surgery and its efficacy is comparable to ondansetron for the first six hours after surgery.", "A prospective, double-blind study was conducted to compare the effect of pressure at the P6 (Neikuan) point with placebo as an antiemetic in children. Sixty-six patients, ages 3-12 yr, undergoing outpatient surgery for correction of strabismus, were allocated randomly to receive either bilateral P6 acupressure or placebo during the perioperative period. The study was designed to detect a 50% difference in the incidence of postoperative vomiting between the two groups, with a 90% power of achieving a statistically significant result at the 5% level (two-tailed). The incidence of postoperative vomiting for the placebo group was 58% before discharge from hospital, 73% at home and 82% in the first 24 h after surgery. The corresponding results for the acupressure group were 58% before discharge, 71% at home and 94% in the first 24 h. These differences were not significant; P6 acupressure did not reduce the incidence of postoperative vomiting in children undergoing strabismus surgery.", "To determine whether the application of acupressure bands would lead to a reduction in postoperative nausea and vomiting after cardiac surgery.\n Prospective, randomized, double-blind clinical trial.\n University-affiliated tertiary care teaching hospital.\n Adult patients undergoing cardiac surgery.\n One hundred fifty-two patients were enrolled to receive either acupressure treatment (n = 75) or placebo (n = 77). All patients had acupressure bands placed on both wrists before induction of anesthesia; those in the treatment group had a bead placed in contact with the P6 point on the forearm.\n Patients were assessed for nausea, vomiting, and pain scores during the first 24 hours of the postoperative period. The incidences of nausea, vomiting, pain scores, and analgesic and antiemetic requirements were similar between the 2 groups. A subgroup analysis by gender implied that acupressure treatment may be effective only in female patients.\n Acupressure treatment did not lead to a reduction in nausea, vomiting, or antiemetic requirements in patients after cardiac surgery.", "We studied the effect of P6 acupressure on 46 women undergoing laparotomy for major gynaecological surgery who received patient-controlled analgesia. Half the patients received acupressure at the P6 site, the remainder received acupressure at a \"sham\" site. There was a reduction in the requests for anti-emetic therapy in the group receiving P6 acupressure but there was no difference in the incidence of nausea and vomiting. There was no difference in total morphine consumption between the two groups.", "One hundred and sixty-two general surgical patients were prospectively randomized to one of three treatments for postoperative nausea and vomiting: (1) acupressure using elasticated bands containing a plastic button to apply sustained pressure at the P6 (Neiguan) point above the wrist, (2) control dummy bands without the pressure button and (3) antiemetic injections of prochlorperazine with each opiate given and as required. All patients received papaveretum injections as required for pain, and additional prochlorperazine injections were prescribed if nausea was not controlled in groups 1 and 2. The severity of nausea was assessed using a linear analogue scale and was significantly (P = 0.002) reduced by acupressure on both days 1 and 2, in comparison to both controls and drug treated patients. The incidence of postoperative vomiting, and the need for unplanned antiemetic injections was also reduced by acupressure but this was not statistically significant. Acupressure can work and should be investigated in other clinical situations.", "To evaluate the effectiveness of acupressure applied at meridian P6 point for prevention of nausea and vomiting in patients undergoing laparoscopic cholecystectomy.\n A randomized double blind study was performed in 50 ASA I and II patients scheduled for laparoscopic cholecystectomy. Patients were divided into two groups; control and placebo. In the control group acupressure was applied at P6 point half an hour before surgery while in the placebo group the acupressure band was tied on meridian P6 point but the plastic bead was placed on the dosum of right forearm away from meridian P6 point. Patients were assessed for nausea and vomiting for six hours after surgery. Anaesthetic technique and postoperative analgesia were standardized for all patients.\n Results showed that the incidence of postoperative nausea and vomiting was 36% in the treatment group and 40% in placebo group, which is statistically insignificant.\n Application of acupressure at P6 point half an hour before induction of anaesthesia does not significantly alter the incidence of postoperative nausea and/or vomiting within 6 hours after surgery.", "Nausea and vomiting are important side effects following administration of epidural morphine for post-Cesarean section pain relief. Stimulation of the P-6 (Neiguan) acupoint is a traditional Chinese acupuncture modality used for antiemetic purpose; it has been found to be effective. The aim of this study was to evaluate the antiemetic effect of P-6 acupressure in parturients given epidural morphine for post-Cesarean section pain relief.\n In a randomized, double-blind and controlled trial, sixty parturients receiving epidural morphine for post-Cesarean section pain relief were investigated. Parturients were allocated to receive the acupressure bands or placebo bands on the P-6 acupoint bilaterally before the administration of spinal anesthesia and were observed over a 48-hour study period.\n The incidence of nausea and vomiting was significantly decreased from 43% and 27% in the control group, to 3% and 0% in the acupressure group, respectively (P < 0.05).\n The results demonstrate that prophylactic use of acupressure bands bilaterally on the P-6 acupoint can significantly reduce incidence of nausea and vomiting after epidural morphine for post-Cesarean section pain relief.", "Acupuncture or acupressure at the Nei-Guan (P.6) point on the wrist produces antiemetic effects in awake but not anesthetized patients. The authors studied whether a combined approach using preoperative acupressure and intra- and postoperative acupuncture can prevent emesis following tonsillectomy in children.\n Patients 2-12 yr of age were randomly assigned to study or placebo groups. Two Acubands with (study) and two without (placebo) spherical beads were applied bilaterally on the P.6 points; non-bead- and bead-containing Acubands, respectively, were applied on the sham points. All Acubands were applied before any drug administration. After anesthetic induction, acupuncture needles were substituted for the beads and remained in situ until the next day. All points were covered with opaque tape to prevent study group identification. A uniform anesthetic technique was used; postoperative pain was managed initially with morphine and later with acetaminophen and codeine. Emesis, defined as retching or vomiting, was assessed postoperatively. Ondansetron was administered only after two emetic episodes at least 2 min apart. Droperidol was added if emesis persisted.\n One hundred patients were enrolled in the study. There were no differences in age, weight, follow-up duration, or perioperative opioid administration between groups. Retching occurred in 26% of the study patients and in 28% of the placebo patients; 51 and 55%, respectively, vomited; and 60 and 59%, respectively, did either. There were no significant differences between the groups. Redness occurred in 8.5% of acupuncture sites.\n Perioperative acupressure and acupuncture did not diminish emesis in children following tonsillectomy.", "Postoperative vomiting causes patients distress and delays discharge after outpatient surgery. Although P6 electroacupuncture is recognized as having an antiemetic effect, its inconvenient instrumentation may limit its clinical applicability. The purpose of this study was to explore a simple and effective alternative method for control of postoperative vomiting in outpatient surgery. We prospectively compared the effect of P6 acupoint injection with 0.2 ml 50% glucose in water (G/W) and intravenous injection of 20 micrograms/kg droperidol for prevention of vomiting in 120 consecutive outpatients undergoing gynecological laparoscopy with general anesthesia. Patients were randomly allocated to receive P6 acupoint injection, i.v. droperidol, or nothing as control group. Both P6 acupoint injection and i.v. droperidol 20 micrograms/kg were found to have a significant antiemetic effect when compared with the control group. We conclude that P6 acupoint injection with 50% G/W is a simple and effective method for reducing the incidence of postoperative emesis in outpatient surgery.", "One hundred unpremedicated female patients of ASA grade 1 or 2 who underwent laparoscopy as outpatients were allocated randomly to one of four groups. All patients received general anaesthesia with fentanyl, thiopentone, halothane, nitrous oxide and oxygen; suxamethonium was given to facilitate tracheal intubation. In the recovery room, group 1 (control) received no treatment; group 2 received electro-acupuncture at the P6 point (Neiguan) on the right side for 15 minutes, group 3 received transcutaneous electrical nerve stimulation at the P6 point on the right side for 15 minutes and group 4 received prochlorperazine 5 mg intravenously. Any act of vomiting, including dry retching, during the first 3 postoperative hours was regarded as postoperative emesis. The incidence of postoperative emesis was 11/25 (44%) in group 1, 3/25 (12%, p less than 0.05) in group 2, 9/25 (36%) in group 3, and 3/25 (12%, p less than 0.05) in group 4. Our results suggest that electro-acupuncture is as effective as prochlorperazine, and may be better than transcutaneous electrical nerve stimulation, in reducing postoperative emesis.", "The efficacy of currently available antiemetics remains poor. Concern with their side effects and the high cost of the newer drugs has led to renewed interest in non-pharmacological methods of treatment. We have studied the efficacy of acupressure at the P6 point in the prevention of nausea and vomiting after laparoscopy, in a double-blind, randomized, controlled study of acupressure vs placebo. We studied 104 patients undergoing laparoscopy and dye investigation. The anaesthetic technique and postoperative analgesia were standardized. Failure of treatment was defined as the occurrence of nausea and/or vomiting within the first 24 h after anaesthesia. The use of acupressure reduced the incidence of nausea or vomiting from 42% to 19% compared with placebo, with an adjusted risk ratio of 0.24 (95% CI 0.08-0.62; P = 0.005). Other variables were similar between groups.", "Electrical stimulation of acupuncture point P6 reduces the incidence of postoperative nausea or vomiting (PONV) in adult patients. However, acupressure, laser stimulation of P6, and acupuncture during anesthesia have not been effective for reducing PONV in the pediatric population. The authors studied the effect of electrical P6 acupuncture in awake pediatric patients who had undergone surgery associated with a high incidence of PONV.\n Patients aged 4-18 yr undergoing tonsillectomy with or without adenoidectomy were randomly assigned to acupuncture, sham acupuncture, or control groups. Acupuncture needles at P6 and a neutral point were placed while patients were anesthetized, and low-frequency electrical stimulation was applied to these points for 20 min in the recovery room while the patients were awake (P6 Acu group). This treatment was compared with sham needles along the arm at acupuncture points not associated with antiemesis (sham group) and a no-needle control group. The arms were wrapped to prevent identification of treatment group, and anesthetic, analgesic, and surgical technique were standardized. Assessed outcomes were occurrence of nausea, occurrence and number of episodes of vomiting, time to vomiting, and use of antiemetic rescue medication.\n One hundred twenty patients were enrolled in the study, 40 per group. There were no differences in age, weight, sex, or opioid administration between groups. The PONV incidence was significantly lower with P6 acupuncture (25 of 40 or 63%; odds ratio, 0.135; number needed to treat, 3.3; P < 0.001) compared with controls (37 of 40 or 93%). Sham puncture had no effect on PONV (35 of 40 or 88%; P = not significant). Occurrence of nausea was significantly less in P6 Acu (24 of 40 or 60%; odds ratio, 0.121; P < 0.01), but not in the sham group (34 of 40 or 85%) compared with the control group (37 of 40 or 93%). Vomiting occurred in 25 of 40 or 63% in P6 Acu; 35 of 40 or 88% in the sham group, and 31 in 40 or 78% in the control group (P = not significant). Patients receiving sham puncture vomited significantly earlier (P < 0.02) and needed more rescue treatment (33 of 40 or 83%; odds ratio, 3.48; P < 0.02) compared with P6 Acu (23 of 40 or 58%) and the control group (24 of 40 or 60%).\n Perioperative P6 electroacupuncture in awake patients significantly reduced the occurrence of nausea compared with the sham and control groups, but it did not significantly reduce the incidence or number of episodes of emesis or the use of rescue antiemetics. Sham acupuncture may exacerbate the severity but not the incidence of emesis. The efficacy of P6 acupuncture for PONV prevention is similar to commonly used pharmacotherapies. Its appropriate role in prevention and treatment of PONV requires further study.", "To evaluate the efficacy of transcutaneous electroacupoint stimulation with a train-of-four (TOF) mode for the prevention of postoperative nausea and vomiting (PONV) in the patients undergoing laparoscopic cholecystectomy.\n Ninety-six ASA Grade I - II patients scheduled for laparoscopic cholecystectomy were randomized into Neiguan (P6) electroacupoint stimulation group (treated group) and a placebo control group (placement of electrodes without electroacupoint stimulation). The anesthetic regimen was standardized by needling at Neiguan on the left side and connecting the TOF peripheral nerve stimulator. The incidence of nausea, vomiting, severity, antiemetic dosage and the degree of pain were assessed at 0, 60, 120 min, and 24 h after surgery.\n The incidence of nausea and vomiting, the dose of antiemetics and the occurrence of severe nausea were all significantly lower in the treated group compared with the control group and the score for pain was obviously reduced in patients of the treated group at 24 h post-operation (P<0.05 or P<0.01).\n Transcutaneous electroacupoint stimulation at P6 with the TOF mode could reduce the incidence and severity of nausea and vomiting with analgesic effects.", "The antiemetic action of stimulation of the P6 (Neiguan) acupuncture (ACP) point has been studied in women, premedicated with nalbuphine 10 mg, undergoing minor gynaecological operations under methohexitone-nitrous oxide-oxygen anaesthesia. Invasive ACP--manual or electrical at 10 Hz--applied for 5 min at the time of administration of the premedication markedly reduced the incidence of vomiting and nausea in the first 6 h after operation, compared with untreated controls. This did not occur with stimulation of a \"dummy\" ACP point outside the recognized ACP meridians. Non-invasive methods (stimulation via a conducting stud or by pressure) were equally as effective as invasive ACP during the early postoperative period. However, both these non-invasive approaches were less effective than invasive ACP in the 1-6 h postoperative period, although each was as effective as two standard antiemetics (cyclizine 50 mg, metoclopramide 10 mg). In view of the total absence of any side effects in more than 500 ACP procedures, the clinical applications of this finding are worthy of further study.", "We randomized 94 patients undergoing cesarean delivery with spinal anesthesia to receive transcutaneous acupoint electrical stimulation using the ReliefBand at the P6 point (active group) or an active ReliefBand applied to the dorsum of the wrist (sham control group). The ReliefBand was applied 30-60 min preoperatively and left in place for 24 h. There was no statistically significant difference between the active and sham control groups in the incidence of intraoperative/postoperative nausea (30% versus 43%/23% versus 41%), vomiting (13% versus 9%/26 versus 37%), need for rescue antiemetics (23% versus 18%/34% versus 39%), or complete response (55% versus 57%/51% versus 34%). There was also no difference between the two groups in nausea scores, number of vomiting episodes, or patient satisfaction with postoperative nausea and vomiting management." ]

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[ "European comparative clinical study of Inerpan: a new wound dressing in treatment of partial skin thickness burns.", "Outpatient management of partial-thickness burns: Biobrane versus 1% silver sulfadiazine.", "DuoDERM hydroactive dressing versus silver sulphadiazine/Bactigras in the emergency treatment of partial skin thickness burns.", "Evaluation of hydrocolloids and topical medication in minor burns.", "Polyurethane film (Opsite) vs. impregnated gauze (Jelonet) in the treatment of outpatient burns: a prospective, randomized study.", "Biobrane versus duoderm for the treatment of intermediate thickness burns in children: a prospective, randomized trial.", "Procutase versus 1% silver sulphadiazine in the treatment of minor burns.", "Comparison of efficacy of 1% silver sulfadiazine and Acticoat for treatment of partial-thickness burn wounds.", "Report on evaluation of hydron film as burn wound dressing.", "Safety and efficacy of a new synthetic burn dressing: a multicenter study.", "Biobrane improves wound healing in burned children without increased risk of infection.", "Biosynthetic skin substitute vs. 1% silver sulfadiazine for treatment of inpatient partial-thickness thermal burns.", "Prospective, randomized study of the efficacy of Mepitel on children with partial-thickness scalds.", "Treatment of partial-thickness burns: a prospective, randomized trial using Transcyte.", "Safety and efficacy of TransCyte for the treatment of partial-thickness burns.", "Clinical effectiveness of alginate silver dressing in outpatient management of partial-thickness burns.", "Management of partial thickness burns with Granuflex 'E' dressings.", "A prospective, randomized trial of Acticoat versus silver sulfadiazine in the treatment of partial-thickness burns: which method is less painful?", "A prospective, randomized trial of silver containing hydrofiber dressing versus 1% silver sulfadiazine for the treatment of partial thickness burns.", "A silicone-coated nylon dressing reduces healing time in burned paediatric patients in comparison with standard sulfadiazine treatment: a prospective randomized trial.", "Biobrane versus 1% silver sulfadiazine in second-degree pediatric burns.", "The effects of an adherent polyurethane film and conventional absorbent dressing in patients with small partial thickness burns.", "Comparison of a hydrocolloid dressing and silver sulfadiazine cream in the outpatient management of second-degree burns.", "Randomized clinical study of Hydrofiber dressing with silver or silver sulfadiazine in the management of partial-thickness burns.", "Prospective clinical study of Hydron, a synthetic dressing, in delivery of an antimicrobial drug to second-degree burns." ]

[ "Eleven European burns centres in five countries (Belgium, England, Germany, Italy, Switzerland) participated in a prospective, randomized clinical trial comparing a new wound dressing Inerpan with conventional dressings such as petroleum jelly gauze, petroleum jelly gauze with antibiotics and silver sulphadiazine cream. The indication was partial skin thickness burns and 62 patients were included. In each patient, two similar lesions (with respect to depth and surface area) were compared, one being treated with Inerpan, the other one with a control dressing. The following parameters were studied: healing time, quality of healing, intensity of pain, local tolerance and frequency of dressing changes. Analysis of the results showed that Inerpan-treated sites healed faster than conventional ones, and were associated with a highly significant reduction of pain. The frequency of dressing changes was greatly reduced and the local tolerance was good.", "A randomized, prospective study comparing the use of Biobrane (group 1) with the use of 1% silver sulfadiazine (group 2) in treating 56 partial-thickness burn wounds was carried out in 52 outpatients with burns that comprised less than 10% of their total body surface area. The two groups were similar in age, gender, race, and extent of burn. Wounds of patients in group 1 (30) were compared with those of group 2 (26) for healing time, pain, compliance with scheduled visits, and costs. Infected and skin-grafted wounds were excluded from healing time analysis. Infection rates of the two groups were similar (three of 30 vs two of 26). One patient in each group underwent skin grafting. Healing times of group 1 wounds were significantly less than those of group 2 (10.6 +/- 0.8 vs 15.0 +/- 1.2 days, P less than .01). Using a pain scale of 1 to 5, Biobrane-treated patients averaged lower pain scores at 24 hours after the burn (1.6 +/- 0.8 vs 3.6 +/- 1.3 P less than .001) and used less pain medication. Compliance with scheduled outpatient visits was also improved in the Biobrane-treated group (88.6% vs 63.2% attendance, P less than .001). Idealized total treatment costs averaged $434 for patients in group 1 compared with $504 for patients in group 2. We conclude that when used on properly selected wounds, Biobrane therapy can significantly decrease pain and total healing time without increasing the cost of outpatient burn care. Improved patient compliance may be an added benefit.", "The study compared DuoDERM Burn Pack Hydroactive Dressings (DHD) with silver sulphadiazine/Bactigras dressings (SSD/Bactigras) in the outpatient management of small partial skin thickness burns. Forty-eight patients were entered into the study, and randomly allocated into either the DHD or SSD/Bactigras group. Burn wounds were followed until complete re-epithelialization occurred. There were no statistical differences between the groups, either with respect to their composition or characteristics of healing in days, and patients' subjective responses to treatment. However, application was easier in the DHD group (93 per cent), compared with 71 per cent in the SSD/Bactigras group (P = 0.0009), and the SSD/Bactigras were easier to remove (96 per cent) versus DHD (66 per cent, P = 0.0004). Furthermore, the DHD group had significantly less dressing changes; a mean of three changes per subject in the DHD group compared with eight in the SSD/Bactigras group (P = 0.117). Two burn wounds became infected in the DHD group, and one in the SSD/Bactigras group. In this study both modalities were found to be equally suitable and effective for small partial skin thickness burns.", "nan", "As it has been shown that re-epithelialization of partial skin thickness wounds can be accelerated if the wound is kept moist, a prospective, randomized clinical study compared the water vapour-semipermeable polyurethane film, Opsite, with the conventional impregnated gauze dressing, Jelonet, in the treatment of outpatient partial skin thickness burns. Fifty-five patients were included: 30 were treated with the polyurethane film and 25 with the conventional dressing. The patients were followed at regular intervals until healing had occurred and were seen 3 months later for evaluation of residual scars and pigmentation. The burns treated with polyurethane films healed with a median of 10 days, while the conventionally treated burns healed with a median of 7 days (P greater than 0.05). Residual scars were noted in 21 per cent of the patients treated with polyurethane films and in 8 per cent treated conventionally (P greater than 0.05). Prophylactic methods should be publicly stressed since one-quarter of the patients were children of 3 years or less who were scalded by split hot liquids. Furthermore the patients' wounds were only briefly cooled before attending medical care. With small burns we advise that cooling should be prolonged until the pain fades then professional assistance should be sought.", "In this study, we directly compared the efficacy of Biobrane and Duoderm for the treatment of small intermediate thickness burns in children in a prospective, randomized fashion to determine their relative impact on wound healing, pain scores, and cost. Patients under 18 years of age with intermediate thickness burns on a surface area less than 10% were enrolled and treated with one of the two dressing systems. Data collected included mechanism of injury, time to complete healing, pain scores, and institutional cost of materials until healing was complete. No significant difference in time to healing or pain scores was detected between the two groups. The cost of each treatment was statistically more expensive in the Biobrane group. The results of this study demonstrate that Duoderm and Biobrane provide equally effective treatment of partial thickness burns among in the pediatric population. However, Duoderm is statistically less expensive than Biobrane and can be considered a first-line treatment option for intermediate thickness burn wounds in children.", "The purpose of this randomised comparative study was to evaluate the use of silver sulphadiazine (SSD) 1% cream (Group A) with the use of Procutase (Group B) in treating burns with a TBSA <10% and a depth not greater than 2nd degree burns and thus suitable for outpatient management. The two groups were similar in age, gender, race, and extent of burn. Procutase is an ionic hydrogel composed of natural hydrophilic polymers in an active ionic solution with an inhibitor of matrix metalloproteinases MMP-1, -3 and -9 (collagenase/gelatinase). Subjects were seen in follow-up biweekly, and wounds of patients in SSD group were compared with those of Procutase group for healing time, pain score at dressing change, compliance with therapy and complication rate. The result of this study showed that Procutase treated patients had statistically significantly less pain and shorter wound healing time. Procutase can be used successfully in patients with burns that do not require hospital admission.\n 2009 Elsevier Ltd and ISBI. All rights reserved.", "Acticoat (Smith & Nephew, Hull, UK) is a silver-coated dressing reported to reduce infection and exhibit antimicrobial activity in wounds.\n The purpose of the present study was to compare the efficacy ofacticoat and 1% silver sulfadiazine (1% AgSD) for treatment of partial thickness burn wounds.\n The authors reviewed 50 patients who had partial thickness burn wounds less than 25% admitted to Siriraj Burn Unit from May 2002 to September 2005. All patients were divided into 2 groups: the acticoat treated group (25 patients) and the 1% silver sulfadiazine treated group (25 patients). The 2 groups were compared for the etiology of burn wound, demographic data including age, sex, % Total Body Surface Area burn (TBSA%), cultured organisms, wound infection and outcome of Length Of hospital Stay (LOS) and level of pain.\n The authors found no significant differences in age, TBSA (%) between both groups. 7 patients (28%) developed wound infection. There were no differences in wound infection and LOS between both groups (p > 0.05). All of the patients who developed wound infection responded well to targeted topical and systemic antibiotic treatment. The 1% AgSD treated group (6 of 25, 24%) obtained more split thickness skin graft to close the granulation defects compared to patients who were treated with acticoat (4 of 25, 16%) but no statistical significance, p = 0.32). Average pain scores in the acticoat treated groups were significantly lower than the 1% AgSD treated group (4 +/- 0.6 versus 5 +/- 0.7, respectively).\n The present study confirms the efficacy of acticoat treatment in partial thickness burn wound. The authors conclude that acticoat has an advantage of limiting the frequency of replacement of the dressing and provides a less painful alternative to wound care with 1% AgSD with comparable incidence of burn wound infection. This is due to its long wear time and the ease of application and removal.", "Hydron Burn Dressing, an amalgam of Polyethylene Glycol-400, and Polyhydroxyethyl methacrylate formed directly on the burn wound has been used in 50 cases with comparable control areas on the same patients which were managed by Polybactrin spray and exposure. The 4-layer film was found to be easily applicable in indoor patients and was pain-free during application and reduced pain after application in superficial burns. It was found to be translucent, pliable, less liable to crack and did not peel off once dried. The rate of infection was found to be 12.5 per cent more than the controls but the healing time was shorter by 2.8 days. Patient's comfort and compliance was better than the scab of the control areas.", "A three-tiered, multicenter study evaluated the safety and efficacy of a new synthetic dressing for burn injuries. The first tier compared use of the test dressing with use of a conventional topical chemotherapeutic agent; the test dressing afforded greater patient comfort, equivalent control of bacterial growth, less frequent dressing change, and possibly faster reepithelialization. Drawbacks included difficulty of application, poor adherence during the first 24 hours after injury, frequent necessity to repair cracks and fissures, and inability to easily monitor burn wounds for bacterial growth. Subsequent tiers were noncomparative but included patients with more severe injuries. The test dressing may be useful in treating superficial and moderate second-degree burns of less than 20% of the total body surface area and possibly in treating iatrogenic \"burn\" wounds such as donor sites. Its use on third-degree burns is not recommended.", "A synthetic bilaminar membrane used as a skin substitute (Biobrane) has been shown to decrease pain and hospitalization in superficial second-degree burns. Despite these benefits, it has not been utilized universally, particularly in young children, due to a perceived increase in related infections. We propose that when this synthetic membrane is applied to superficial scald burns <25% of the total body surface area (TBSA), decreased healing times are expected without increased risk of infection. Between 1994-1999, 89 children treated within 48 h after receiving superficial partial thickness scald burns covering 5-25% TBSA with no indication of infection were seen at our hospital. Forty-one were assigned randomly to receive treatment with the skin substitute Biobrane and 48 to receive conservative treatment with topical antimicrobials and dressing changes. Comparisons of treatment were made between groups for length of hospitalization, wound healing times, and infectious complications. Children treated with Biobrane or topical antimicrobials were similar in age, race, sex, %TBSA burned, and location of burn. Those receiving Biobrane had shorter hospitalizations and healing times, which was significant for both infants and toddlers and older children. Treatment groups were not different in the use of systemic antibiotics or readmissions for infectious complications. Biobrane was removed in 5.9% of cases for non-adherence. The application of Biobrane within 48 h of superficial burns provides for shorter hospitalizations and faster healing times in children of all ages without increased risk of infection.", "When used appropriately on superficial or moderate-depth partial-thickness burns, Biobrane significantly decreased total healing time to complete reepithelialization, reduced pain, and was associated with decreased nursing time and costs when compared to 1% silver sulfadiazine cream. Care must be used in selecting wounds for Biobrane therapy. They must be fresh, noninfected, and free of eschar and debris with a moist, sensate surface that demonstrates capillary blanching and refill. Wounds must be inspected regularly for nonadherence and signs of infection. Early fluid accumulation requires prompt aspiration. Biobrane should be removed if fluid reaccumulates or the Biobrane becomes nonadherent at any time after 48 hours. When used appropriately, Biobrane offers significant advantages over conventional therapy of acute partial-thickness burns.", "We performed a randomized clinical trial in which children with partial-thickness scald burns of less than 15% total body surface area were assigned treatment with either Mepitel (Mölnlycke Health Care) or silver sulfadiazine. Data were collected on time to wound healing, pain at dressing change, infection, and resource use. Student's t and chi-square tests were used to determine differences in the two groups. Healing times were compared using Kaplan-Meier survival curves. Wounds of children treated with Mepitel healed significantly faster than did controls' (p < 0.001), exhibited less eschar formation (p < 0.05), and experienced less pain at dressing change (p < 0.05). They also had significantly lower mean daily hospital charges ($1937 vs $2316; p = 0.025); as well as significantly lower charges for dressing changes and narcotics. There was no significant difference in wound infection. We believe the use of Mepitel represents a significant advance in the treatment of partial-thickness scald wounds in children.", "The purpose of the present study was to compare the effectiveness of three burns dressings (TransCyte, a bio-engineered skin substitute; Biobrane; and Silvazine cream (silver sulphadiazine and 0.2% chlorhexidine)), in treating children with partial-thickness burns. The primary objective was to determine the days until > or =90% re-epithelialization. The secondary objectives were to evaluate the number of wounds requiring autografting and the number of dressing changes/local wound care required.\n Study wounds were identified on each patient and the patients were randomized to receive TransCyte or Biobrane or Silvazine. Assessment of study wound closure began at 2 days after treatment and continued at least every other day thereafter until the wounds re-epithelialized or were autografted. A laser Doppler imaging system was used as an adjunct to assessing the depth of the burn.\n Thirty-three patients with 58 wound sites enrolled in the study (TransCyte, n = 20, Biobrane, n = 17; Silvazine, n = 21). Mean time to re-epithelialization was 7.5 days for TransCyte, 9.5 days for Biobrane, and 11.2 days for Silvazine. The number of wounds requiring autografting were 5/21 (24%) for Silvazine, 3/17 (17%) for Biobrane, and 1/20 (5%) for TransCyte.\n When used in partial-thickness burns in children, TransCyte promotes fastest re-epithelialization and required less overall dressings then Biobrane or Silvazine. Patients who received Silvazine or Biobrane require more autografting than those treated with TransCyte.", "Standard treatment for extensive partial-thickness burns in the United States and in much of the world involves the application of topical antimicrobial agents and repetitive wound débridements and dressing changes. We evaluated a new biologic wound covering, TransCyte (Advanced Tissue Sciences, La Jolla, Calif, formerly marketed as Dermagraft-Transitional Covering), for the treatment of partial-thickness burns. This material is composed of human newborn fibroblasts which are then cultured on the nylon mesh of Biobrane (Dow B. Hickam, Inc, Sugarland, Tex); the thin silicone membrane bonded to the mesh provides a moisture vapor barrier for the wound. A prospective, randomized, comparison study of silver sulfadiazine and TransCyte was performed with the use of paired wound sites on 14 patients. Wounds treated with TransCyte healed more quickly (mean 11.14 days to 90% epithelialization vs 18.14 days, P = .002). A noncomparison evaluation was then done for an additional 18 patients, and it confirmed excellent wound healing and an absence of infections. There were no infections in the 32 wound sites treated with TransCyte. In the first study group, late wound evaluations (3, 6, and 12 months postburn) were performed with use of the Vancouver Scar Scale. The results indicated that wound sites treated with TransCyte healed with less hypertrophic scarring than sites treated with silver sulfadiazine (P < .001 at 3 and 6 months, P = .006 at 12 months).", "Askina Calgitrol Ag(®) (B. Braun Hospicare Ltd, Collooney Co. Sligo, Ireland), alginate silver wound dressing, is an advanced wound dressing which combines the potent broad-spectrum antimicrobial action of silver with enhanced exudate management properties of calcium alginate and polyurethane foam. The purpose of this study was to compare the efficacy of Askina Calgitrol Ag(®) and 1% silver sulfadiazine (1% AgSD) in the outpatient management of partial-thickness burn wounds at Burn Unit, Siriraj Hospital. A prospective descriptive study was conducted between January 2008 and January 2009 in Burn Unit, Division of Trauma Surgery, Siriraj Hospital, Mahidol University, Thailand. The 65 patients with partial-thickness burn wounds, less than 24 hours post-burn injury, had a total body surface area (TBSA%) less than 15% were treated at Siriraj Outpatient Burn Clinic. All patients were divided into Askina Calgitrol Ag(®) treated group (30 patients) and 1% AgSD treated group (35 patients). The data were compared by the demographics including age, gender, % TBSA burn, pain score, number of wound dressing change, nursing time and time of wound healing. Patients included in both groups were comparable with no significant differences in demographic data of age, gender, location of burn and type of burn injury (P > 0·05 evaluated by paired Student's t-test) between both group. The present results showed that average pain scores in the Askina Calgitrol Ag(®) treated group were significantly lower than the 1% AgSD treated group (2·23 ± 1·87 versus 6·08 ± 2·33, respectively) between both groups (P < 0·02). Patients treated with Askina Calgitrol Ag(®) had significantly lower number of wound dressing change (P < 0·02) and nursing time (P < 0·02) compared with 1% AgSD treated group. The Askina Calgitrol Ag(®) group needed less frequent wound dressing. Healing time was 7 ± 3·51 days after the application of Askina Calgitrol Ag(®). This was significantly shorter than that of control wounds (14 ± 4·18 days). Application of Askina Calgitrol Ag(®) leads to a good burn wound outcome. The present study confirms the effectiveness of Askina Calgitrol Ag(®) in the outpatient management of partial-thickness burn wounds.\n © 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd and Medicalhelplines.com Inc.", "In a prospective, open, randomized and parallel group trial, 98 patients with partial thickness burns suitable for outpatient management were treated with either Granuflex 'E' (n = 49) or Bactigras (n = 49). The objective was to compare the safety, efficacy and performance characteristics of Granuflex 'E' with Bactigras. The overall rating of the dressing by the investigators and the patients showed a significant preference for Granuflex 'E'. In addition, the quality of healing was rated as 'excellent' in 56 per cent of patients treated with Granuflex 'E', compared with only 11 per cent in the group treated with the conventional dressing. Granuflex 'E' is safe, effective and flexible and we recommend that it should be used as the first-choice dressing in the management of partial skin thickness burns.", "Despite recent improvements in analgesia, pain control during dressing changes continues to be a major challenge in patients with burns. We investigated two different dressing modalities to compare how much pain the patient experienced during and after the dressing change. Patients with partial-thickness burns that required only topical wound care were assigned randomly to treatment with Acticoat (Smith and Nephew USA, Largo, FL) or silver sulfadiazine (AgSD). The outcome variable was pain during wound care, which was measured using visual analog pain scores. The mean visual analog pain scores for the wounds treated with Acticoat or AgSD wounds were 3.2 and 7.9, respectively (P < .0001; paired Student's t-test). In 41 of the 47 paired pain score observations, the pain in the wound treated with AgSD was perceived as greater than in the wound treated with Acticoat. Burn wound care with Acticoat is less painful than burn wound care with AgSD in patients with selected partial-thickness burns.", "Silver sulfadiazine has been used as a topical burn wound treatment for many years. Pain associated with dressing changes is a common problem in burn wounds. Aquacel Ag, a hydrofiber dressing coated with ionic silver has been reported to reduce burn wound infection and promote antimicrobial activity. The purpose of this study was to show the benefits of Aquacel Ag for the treatment of partial thickness burns. This prospective randomized study was conducted in 70 patients who had partial thickness burns less than 15% of total body surface area and were treated at Siriraj outpatient burn clinic during December 2006-February 2008. Patients were divided into two groups: Aquacel Ag-treated group with dressing changes every 3 days (35 patients) and 1% silver sulfadiazine-treated group, with daily dressing changes (35 patients). There was no difference in demographic data including age, gender, burn percentage between groups. Time-to-wound healing pain score during dressing change and cost of treatment were compared between both groups. Time-to-wound closure was significantly shorter in the Aquacel Ag-treated group (10 +/- 3 versus 13.7 +/- 4 days, P < 0.02) as well as pain scores at days 1, 3 and 7 (4.1 +/- 2.1, 2.1 +/- 1.8, 0.9 +/- 1.4 versus 6.1 +/- 2.3, 5.2 +/- 2.1, 3.3 +/- 1.9, respectively, P < 0.02). Total cost of treatment was 52 +/- 29 US dollars for the Aquacel Ag-treated group versus 93 +/- 36 US dollars for the silver sulfadiazine-treated group. This study showed that Aquacel Ag increased time to healing, decreased pain symptoms and increased patient convenience because of limiting the frequency of replacement of the dressing at lower total cost. This study confirms the efficacy of Aquacel Ag for the treatment of partial thickness burns at an outpatient clinic.", "Mepitel is a new grid like silicone coated nylon dressing containing no additional biological compounds. We describe a prospective randomized pilot study comparing Mepitel to the standard silver sulfadiazine cream (Flamazine) dressing for the topical treatment of paediatric burns. Seventy-six children presenting within 24 h of injury with a non previously treated burn were randomly assigned to Mepitel treatment (group M) or Flamazine treatment (group F). Age, sex, surface area of burn and causal agent were noted at admission. The depth of the burn, cumulative number of dressings, presence or absence of a complete epithelial cover, infection, bleeding and allergy were noted at each dressing change. There were 41 children in group M and 35 children in group F. Five children were subsequently withdrawn from each group because they required skin grafting. Analysis of the above mentioned criteria showed no statistical difference between the two groups except for the healing time (group M: 7.58+/-3.12, group F: 11.26+/-6.02, p < 0.01) and the number of dressings (group M: 3.64+/-1.5, group F: 5.13+/-2.9, p < 0.05). Mepitel has proved to be an easy-to-remove dressing, adhering only to intact skin. The faster healing time found in the Mepitel group may be related to a direct effect of silicone on epithelial growth or to a decrease in surface-cell damage compared to the silver sulfadiazine group. This attractive product will be further assessed on a larger scale trial to confirm our observations.", "Partial-thickness burns in children have been treated for many years by daily, painful tubbing, washing, and cleansing of the burn wound, followed by topical application of antimicrobial creams. Pain and impaired wound healing are the main problems. We hypothesized that the treatment of second-degree burns with Biobrane is superior to topical treatment. Twenty pediatric patients were prospectively randomized in two groups to compare the efficacy of Biobrane versus 1% silver sulfadiazine. The rest of the routine clinical protocols were followed in both groups. Demographic data, wound healing time, length of hospital stay, pain assessments and pain medication requirements, and infection were analyzed and compared. Main outcome measures included pain, pain medication requirements, wound healing time, length of hospital stay, and infection. The application of Biobrane to partial-thickness burns proved to be superior to the topical treatment. Patients included in the biosynthetic temporary cover group presented with less pain and required less pain medication. Length of hospital stay and wound healing time were also significantly shorter in the Biobrane group. None of the patients in either group presented with wound infection or needed skin autografting. In conclusion, the treatment of partial-thickness burns with Biobrane is superior to topical therapy with 1% silver sulfadiazine. Pain, pain medication requirements, wound healing time, and length of hospital stay are significantly reduced.", "nan", "The purpose of this prospective randomized study was to evaluate the use of an occlusive hydrocolloid dressing (Duoderm hydroactive, Squibb) and silver sulfadiazine (Silvadene, Marion) cream in the outpatient management of second-degree burns. The inclusion criteria consisted of burns less than 15% total body surface area that were evaluated within 24 hours of injury and did not require hospital admission. Fifty patients were randomly assigned after having been screened through a list of seven exclusion criteria. On initial evaluation the burns were photographed and screened for causative agent, location, size, depth, tetanus status, and presence of associated burns and injuries. Patients were seen in followup at least biweekly and evaluated for wound bed healing, wound margin healing, pain, number of dressing changes between visits, and ease of dressing application and removal. On final evaluation the burns were photographed and inspected for appearance of the healed burn, repigmentation, wound contraction, approximate time for dressing change, patient compliance, limitation of activity, overall impression of the treatment, and number of days for complete healing. Results were compared using a two-tailed t-test with p less than 0.01. Both groups were statistically similar in age, sex, and size. Duoderm-treated burns had statistically significantly better wound healing, repigmentation, less pain, fewer dressing changes, less time for dressing changes, and less cost. Duoderm-treated patients had statistically significantly less limitation of activity, better patient compliance, greater patient comfort, better overall acceptance, and felt the treatment was more aesthetically pleasing. The results reveal that the Duoderm Hydroactive dressings are superior to Silvadene cream in the outpatient management of second-degree burns.", "This prospective, randomized study compared protocols of care using either AQUACEL Ag Hydrofiber (ConvaTec, a Bristol-Myers Squibb company, Skillman, NJ) dressing with silver (n = 42) or silver sulfadiazine (n = 42) for up to 21 days in the management of partial-thickness burns covering 5% to 40% body surface area (BSA). AQUACEL Ag dressing was associated with less pain and anxiety during dressing changes, less burning and stinging during wear, fewer dressing changes, less nursing time, and fewer procedural medications. Silver sulfadiazine was associated with greater flexibility and ease of movement. Adverse events, including infection, were comparable between treatment groups. The AQUACEL Ag dressing protocol tended to have lower total treatment costs (Dollars 1040 vs. Dollars 1180) and a greater rate of re-epithelialization (73.8% vs 60.0%), resulting in cost-effectiveness per burn healed of Dollars 1,409.06 for AQUACEL Ag dressing and Dollars 1,967.95 for silver sulfadiazine. A protocol of care with AQUACEL(R) Ag provided clinical and economic benefits compared with silver sulfadiazine in patients with partial-thickness burns.", "This clinical trial prospectively evaluates the potential beneficial effects of antimicrobial drug delivery from a synthetic dressing (Hydron-AgSD) formed on second-degree burn wounds. A paste composed of polyethylene glycol-400, poly 2-OH ethylmethacrylate, and silver sulfadiazine (AgSD 1%-3%) matured within one hour to form a solid dressing. In 27 patients, comparable areas of second-degree wounds on the same patient were selected at random for test and control (silver sulfadiazine 1% only) sites. The mean total time of the synthetic dressing application per patient was about nine days, and each dressing remained in place for nearly four days. During this interval the control sites required four dressings changes. In 17 tests for infections, the control areas were contaminated but no bacteria were detected under the synthetic dressing; in three tests, the controls had no bacteria, whereas the synthetic dressing did. Healing of burns was similar under both types of dressing. Benefits of Hydron treatment included increased patient comfort because of the reduced number of dressing changes and, in some cases, greater freedom from contaminating bacteria." ]

[ "9074573", "7838584", "8584148", "11166969", "10215688", "11964590", "14594148", "3281774", "15800228", "12583865", "12654955", "11240090", "9633737", "11865132", "12660386", "1712433", "11159256", "1663226", "14499422", "1350803", "12370455", "8665549", "2454440" ]

[ "Randomised double-blind active-placebo-controlled crossover trial of intravenous fentanyl in neuropathic pain.", "Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid receptor antagonist ketamine: a double-blind, cross-over comparison with morphine and placebo.", "Central dysesthesia pain after traumatic spinal cord injury is dependent on N-methyl-D-aspartate receptor activation.", "The effect of opioids on phantom limb pain and cortical reorganization.", "Prolonged analgesic effect of ketamine, an N-methyl-D-aspartate receptor inhibitor, in patients with chronic pain.", "Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized double-blind, active placebo-controlled, crossover trial.", "Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial.", "Association of pain relief with drug side effects in postherpetic neuralgia: a single-dose study of clonidine, codeine, ibuprofen, and placebo.", "Morphine, gabapentin, or their combination for neuropathic pain.", "Cold allodynia and hyperalgesia in neuropathic pain: the effect of N-methyl-D-aspartate (NMDA) receptor antagonist ketamine--a double-blind, cross-over comparison with alfentanil and placebo.", "Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial.", "Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.", "Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia.", "Effects of IV morphine in central pain: a randomized placebo-controlled study.", "Oral opioid therapy for chronic peripheral and central neuropathic pain.", "Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia.", "The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study.", "Morphine differentially affects the sensory and affective pain ratings in neurogenic and idiopathic forms of pain.", "Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy.", "Morphine responsiveness of chronic pain: double-blind randomised crossover study with patient-controlled analgesia.", "Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial.", "Intravenous infusion of the NMDA antagonist, ketamine, in chronic posttraumatic pain with allodynia: a double-blind comparison to alfentanil and placebo.", "Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain." ]

[ "The effectiveness of opioid analgesics in non-cancer neuropathic pain is unpredictable and can be disappointing. It is not clear whether opioids, when effective, relieve pain by decreasing pain intensity or pain unpleasantness or by their sedative effect. The aim of this prospective randomised double-blind placebo-controlled crossover trial was to assess relief of pain intensity and pain unpleasantness with intravenous infusions of fentanyl.\n We compared the analgesic effect of intravenous dose titration of fentanyl with diazepam (active placebo) or saline (inert placebo) in 53 patients with different types of neuropathic pain. Patients were randomly assigned two consecutive infusions: fentanyl plus diazepam (27 patients) or fentanyl plus saline (26 patients). Study medication was infused at a constant rate for a maximum of 5 h. Pain, sedation, and side-effects were assessed from the start of infusion for 8 h. The primary outcome measure was maximum relief of pain intensity.\n One patient in the fentanyl/diazepam group and two in the fentanyl/saline group were withdrawn. Maximum relief of pain intensity was better with fentanyl than with diazepam (66% [95% CI 53-80] vs 23% [12-35]) or with saline (50% [36-63] vs 12% [4-20]). The beneficial effect of fentanyl was independent of the type of neuropathic pain and the degree of sedation. Fentanyl therapy produced equal relief of pain intensity and pain unpleasantness, whereas diazepam and saline did not reduce either pain index. Patients reported significantly more side-effects while receiving fentanyl than during diazepam or saline infusion (p < 0.0001), but none of the side-effects was severe.\n Fentanyl may relieve non-cancer neuropathic pain by its intrinsic analgesic effect. The clinical characteristics of neuropathic pain do not predict response to opioids.", "Pain and sensory thresholds were examined before and after intravenous administration of ketamine (0.15 mg/kg), morphine (0.075 mg/kg) or saline in 8 patients with post-herpetic neuralgia. A randomized, double-blind, cross-over study design was used. Post-herpetic neuralgia was associated with impaired sensory function, as shown by reduced tactile and warm sensation in the affected compared with the contralateral non-affected skin area. Neither ketamine nor morphine changed significantly the thresholds for warm, cold, heat pain or tactile sensation. However, ketamine normalized abnormal heat pain sensations in 4 patients, probably due to a central effect. Ketamine, but not morphine, produced significant relief of pain. Pain evoked by non-noxious stimulation of the skin (allodynia) was significantly inhibited by ketamine as well as by morphine. Wind-up-like pain (i.e., pain evoked by repeatedly pricking the affected skin area) was significantly inhibited by ketamine, but significantly aggravated by morphine. Side effects were observed in all the 8 patients after injection of ketamine and in 6 patients after injection of morphine. The present results support the hypothesis that the N-methyl-D-aspartic acid (NMDA) receptors are involved in the control of post-herpetic neuralgia including allodynia and wind-up-like pain. The NMDA receptors also may play a role in the modulation of thermal perception.", "The role of central N-methyl-D-aspartate (NMDA) receptors in the pathogenesis of central pain was examined in nine patients with central dysesthesia pain after spinal cord injury. The central pain syndrome included spontaneous continuous and intermittent pain as well as evoked pain. Pain was evoked by non-noxious stimulation of the skin (allodynia) and by repeated pricking of the skin (wind-up-like pain). The severity of continuous and evoked pain was examined before and after the intravenous infusion of either the NMDA receptor antagonist ketamine (6 micrograms/kg/min after a bolus dose of 60 micrograms/kg), the mu-opioid receptor agonist alfentanil (0.6 microgram/kg/min after after a bolus dose of 7 micrograms/kg), or placebo (0.9% NaCl). A randomized, double-blind, crossover study design was used. It was found that both continuous and evoked pain were markedly reduced by the blockade of NMDA receptors by ketamine as well as by the activation of mu-opioid receptors by alfentanil. Neither ketamine nor alfentanil significantly changed thresholds for the sensation of heat pain. The reduction of pain was not associated with severe side effects; the most severe side effect of ketamine was bothersome dizziness in one patient, and only modest side effects were caused by alfentanil. The present data provide clinical evidence that the development of central dysesthesia pain after traumatic spinal cord injury is dependent on the activation of central NMDA receptors. The results further indicate that mu-opioid receptors are involved in the control of this type of pain.", "The efficacy of oral retarded morphine sulphate (MST) was tested against placebo in a double-blind crossover design in 12 patients with phantom limb pain after unilateral leg or arm amputation. Two counterbalanced treatment phases of 4 weeks each were initiated with an intravenous test infusion of MST or Placebo. The titration phase was 2 weeks. The dose of MST was titrated to at least 70 mg/day and at highest 300 mg/day. Pain intensity was assessed hourly on visual analog scales during a 4-week treatment-free phase, both treatment phases and at two follow-ups (6 and 12 months). Reorganization of somatosensory cortex, electric perception and pain thresholds as well as selective attention were measured pre- and post-treatment. A significant pain reduction was found during MST but not during placebo. A clinically relevant response to MST (pain reduction of more than 50%) was evident in 42%, a partial response (pain reduction of 25-50%) in 8% of the patients. Neuromagnetic source imaging of three patients showed initial evidence for reduced cortical reorganization under MST concurrent with the reduction in pain intensity. Perception and pain thresholds were not significantly altered whereas attention was significantly lower under MST. Thus, opioids show efficacy in the treatment of phantom limb pain and may potentially influence also cortical reorganization. These data need to be replicated in larger patient samples.", "We examined the role of N-methyl-D-aspartate (NMDA) receptors in chronic (pathological) pain in humans by using the NMDA receptor antagonist ketamine as a probe. Thirty patients with neuropathic pain in the trigeminal area were given an i.m. injection of ketamine 0.4 mg/kg combined with midazolam 0.05 mg/kg. Pethidine 1.0 mg/kg served as a control. Three different response patterns were observed. Ketamine caused a long-term (6-24 h) analgesic effect partly dissociated from the mental side effects in 8 of the 26 patients who completed the study; these patients also had a slight analgesic effect of pethidine. In nine patients, ketamine caused a short-lasting (<2 h) analgesic effect closely associated with the mental side effects, whereas pethidine caused little or no analgesia. The remaining nine patients did not experience any reduction of pain after either drug in spite of characteristic side effects. One week after the i.m. challenge the patients received either 4.0 mg/kg ketamine hydrochloride or placebo capsules to be taken orally as a nightly dose for three consecutive nights. Five of the eight patients who had a long-term analgesic effect of the i.m. challenge reported decreased pain on days after ketamine. None of the others reported an analgesic effect. The phenomenon of long-term depression of pain in a subgroup of patients was thus confirmed when ketamine was given p.o. These findings indicate that NMDA receptors are involved in the perception and maintenance of pathological pain in some patients. In others, pain appears to be mediated by NMDA receptor-independent mechanisms. We suggest that NMDA receptor-independent transmission in central pain pathways may contribute to the reduced efficiency of analgesic drugs often seen in chronic pain states.", "Phantom and stump pains, common sequelae of limb amputations, are significant impediments to rehabilitation of amputees. The pathophysiology and optimal treatment of postamputation pain states are unclear. While stump pain may result from neuromas in the stump, phantom pain is thought to be related to cortical reorganization. The authors hypothesized that morphine and lidocaine may have differential effectiveness on stump and phantom pains.\n The authors conducted a randomized double-blind, active-placebo-controlled, crossover trial to compare the analgesic effects of intravenous morphine and lidocaine on postamputation stump and phantom pains. An intravenous bolus followed by an intravenous infusion of morphine (0.05 mg/kg bolus + 0.2 mg/kg infusion over 40 min), lidocaine (1 mg/kg bolus + 4 mg/kg infusion) and the active placebo, diphenhydramine (10 mg bolus + 40 mg infusion), were performed on three consecutive days. Phantom and stump pain ratings and sedation scores were recorded at 5-min intervals using a 0-100 visual analog scale. Pain measures were initiated 30 min before drug infusion and continued until 30 min after the end of infusion. Subjects' self-reported pain relief and satisfaction were assessed at the end of each infusion.\n Thirty-one of 32 subjects enrolled completed the study. Eleven subjects had both stump and phantom pains, 11 and 9 subjects had stump and phantom pain alone, respectively. Baseline pain scores were similar in the three drug groups. Compared with placebo, morphine reduced both stump and phantom pains significantly (P < 0.01). In contrast, lidocaine decreased stump (P < 0.01), but not phantom pain. The changes in sedation scores for morphine and lidocaine were not significantly different from placebo. Compared with placebo, self-reported stump pain relief was significantly greater for lidocaine (P < 0.05) and morphine (P < 0.01), while phantom pain relief was greater only for morphine (P < 0.01). Satisfaction scores were significantly higher for lidocaine (mean +/- SD: 39.3 +/- 37.8, P < 0.01) and morphine (45.9 +/- 35.5, P < 0.01) when compared with placebo (9.6 +/- 21.0).\n Stump pain was diminished both by morphine and lidocaine, while phantom pain was diminished only by morphine, suggesting that the mechanisms and pharmacological sensitivity of stump and phantom pains are different.", "The analgesic effectiveness and adverse effect incidence of a daily dose of 10 or 20 mg of oral methadone were evaluated in 18 patients with a diverse range of chronic neuropathic pain syndromes, who had all responded poorly to traditional analgesic regimens. Analgesia was seen after each dose of methadone. As compared with placebo, the 20 mg daily dose (given as 10 mg bd) resulted in statistically significant (P = 0.013-0.020) improvements in patient Visual Analogue Scale ratings of maximum pain intensity, average pain intensity and pain relief, recorded at the same time daily. The analgesic effects extended over 48 hours, as shown by statistically significant (P = 0.013-0.020) improvements in all three outcomes on the rest days instituted between each daily dose. Analgesic effects (lowered maximum pain intensity and increased pain relief, on the day of dosing only) were also seen when the lower daily dose of 10 mg methadone (given as 5 mg bd) was used, but these failed to reach statistical significance (P = 0.064 and 0.065, respectively). Interpatient analysis showed that the analgesic effects were not restricted to any particular type of neuropathic pain. Patient compliance was high throughout the trial. One patient withdrew during the 10 mg and six during the 20 mg methadone treatment periods. This is the first double-blind randomized controlled trial to demonstrate that methadone has an analgesic effect in neuropathic pain.", "In a randomized, double-blind crossover study, 40 patients with postherpetic neuralgia were given single oral doses of clonidine, 0.2 mg, codeine, 120 mg, ibuprofen, 800 mg, or inert placebo. Pain relief and side effects were recorded for 6 hours. Patients reported significantly more relief after clonidine than after the other three treatments. Codeine and ibuprofen were ineffective. Sedation, dizziness, and other side effects were more frequent after clonidine (74%) or codeine (69%) than after placebo (36%) or ibuprofen (28%). Reported pain relief was greater during trials in which side effects were present. A single, mild side effect was associated with as much additional pain relief as multiple, severe side effects. Clonidine's superiority to codeine, which had a similar incidence of side effects, argues for a specific analgesic effect. In addition, side effects may have contributed to clonidine analgesia, perhaps by suggesting to patients that they had received a potent drug.", "The available drugs to treat neuropathic pain have incomplete efficacy and dose-limiting adverse effects. We compared the efficacy of a combination of gabapentin and morphine with that of each as a single agent in patients with painful diabetic neuropathy or postherpetic neuralgia.\n In this randomized, double-blind, active placebo-controlled, four-period crossover trial, patients received daily active placebo (lorazepam), sustained-release morphine, gabapentin, and a combination of gabapentin and morphine--each given orally for five weeks. The primary outcome measure was mean daily pain intensity in patients receiving a maximal tolerated dose; secondary outcomes included pain (rated according to the Short-Form McGill Pain Questionnaire), adverse effects, maximal tolerated doses, mood, and quality of life.\n Of 57 patients who underwent randomization (35 with diabetic neuropathy and 22 with postherpetic neuralgia), 41 completed the trial. Mean daily pain (on a scale from 0 to 10, with higher numbers indicating more severe pain) at a maximal tolerated dose of the study drug was as follows: 5.72 at baseline, 4.49 with placebo, 4.15 with gabapentin, 3.70 with morphine, and 3.06 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). Total scores on the Short-Form McGill Pain Questionnaire (on a scale from 0 to 45, with higher numbers indicating more severe pain) at a maximal tolerated dose were 14.4 with placebo, 10.7 with gabapentin, 10.7 with morphine, and 7.5 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). The maximal tolerated doses of morphine and gabapentin were lower (P<0.05) with the combination than for each drug as single agent. At the maximal tolerated dose, the gabapentin-morphine combination resulted in a higher frequency of constipation than gabapentin alone (P<0.05) and a higher frequency of dry mouth than morphine alone (P<0.05).\n Gabapentin and morphine combined achieved better analgesia at lower doses of each drug than either as a single agent, with constipation, sedation, and dry mouth as the most frequent adverse effects.\n Copyright 2005 Massachusetts Medical Society.", "Cold allodynia and hyperalgesia are frequent clinical findings in patients with neuropathic pain. While there have been several clinical studies showing the involvement of central sensitization mechanisms and N-methyl-D-aspartate (NMDA) receptor activation in mechanical allodynia/hyperalgesia and ongoing pain, the mechanisms of thermal allodynia and hyperalgesia have received less attention. The aim of the present study was to examine the effect of the NMDA-receptor antagonist ketamine on thermal allodynia/hyperalgesia, ongoing pain and mechanical allodynia/hyperalgesia in patients with neuropathic pain (11 patients with post-traumatic neuralgia and one patient with post-herpetic neuralgia). All the patients were known to suffer from severe cold allodynia (cold pain detection threshold (CPDT): 23.8 degrees C, median value). The mu-opioid agonist alfentanil was used as an active control. The study design was double-blind and placebo-controlled and the drugs were administered i.v. (bolus dose and infusion). CPDT in the asymptomatic contralateral area was found to be significantly decreased (cold allodynia) compared to CPDT in site- and age-matched normal controls. Heat pain detection thresholds were found to be normal and no consistent heat hyperalgesia occurred. Alfentanil significantly reduced cold allodynia (by increasing CPDT) in symptomatic area (P=0.0076). Ketamine did not significantly increase the threshold. Significant and marked reductions of hyperalgesia to cold (visual analogue score at threshold value) were seen following both alfentanil (4.5 before, 1.4 after, median value) and ketamine (6.8 before, 0.4 after, median value). Alfentanil and ketamine also significantly reduced ongoing pain and mechanical hyperalgesia. It is concluded that NMDA-receptor mediated central sensitization is involved in cold hyperalgesia, but since CPDT remained unaltered, it is likely that other mechanisms are present.", "Opioid treatment has played a limited role in the management of diabetic neuropathy, in part because of concerns about the responsiveness of neuropathic pain to opioid treatment. This controlled study evaluated the efficacy and safety of controlled-release (CR) oxycodone in subjects with moderate to severe pain due to diabetic neuropathy.\n This multicenter, randomized, double-blind, placebo-controlled, parallel-group study included 159 subjects with moderate to severe pain due to diabetic neuropathy. Treatment began with either one 10-mg tablet of CR oxycodone (n = 82) or identical placebo (n = 77) every 12 hours. Doses could be increased every 3 days to a maximum of 6 tablets (60 mg CR oxycodone) every 12 hours. Treatment lasted up to 6 weeks. The primary efficacy variable was overall average daily pain intensity during study days 28 to 42.\n At an average (SD) dose of 37 (21) mg per day (range 10 to 99 mg/d), CR oxycodone provided more analgesia than placebo (p= 0.002) in the intent-to-treat cohort. From days 28 to 42, overall average daily pain intensity (least squares mean +/-SE), rated in subject diaries on a numeric scale of 0 (no pain) to 10 (pain as bad as you can imagine), was 4.1 +/- 0.3 in subjects given CR oxycodone and 5.3 +/- 0.3 in placebo-treated subjects. Overall, 80 (96%) of 82 subjects given CR oxycodone and 52 (68%) of 77 subjects who received placebo reported adverse events. The most common adverse events in the CR oxycodone group were opioid related.\n In this 6-week trial, CR oxycodone was effective for the treatment of moderate to severe pain due to diabetic neuropathy. Adverse events were typical of opioid-related side effects.", "Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each infusion and each targeted plasma level, baseline vital signs, neurosensory testing that included thermal thresholds, thermal pain and von Frey filament thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were mapped at the beginning and the end of each infusion. A total of seven males and five females with post-nerve injury allodynia and hyperalgesia were enrolled in the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds were noted. Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions. In addition, alfentanil showed a statistically significant dose-dependent reduction in both spontaneous and von Frey pain scores. Both the alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic area and ketamine showed a significant reduction in the von Frey hyperalgesia area. No significant CNS side effects and changes in vital signs were noted. A partial deafferentation state was found in the post-nerve injury patients who presented with allodynia and hyperalgesia. The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect. In addition, the reduction of the hyperalgesic area and evoked pain scores with the alfentanil infusion suggests that opioids may have some peripheral effects in the post-nerve injury patients. Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.", "Although opioid analgesics are used in the management of neuropathic pain syndromes, evidence of their efficacy remains to be established. We evaluated the clinical efficacy and safety of oxycodone in neuropathic pain using postherpetic neuralgia as a model.\n Patients with postherpetic neuralgia of at least moderate intensity were randomized to controlled-release oxycodone 10 mg or placebo every 12 hours, each for 4 weeks, using a double-blind, crossover design. The dose was increased weekly up to a possible maximum of 30 mg every 12 hours. Pain intensity and pain relief were assessed daily, and steady (ongoing) pain, brief (paroxysmal) pain, skin pain (allodynia), and pain relief were recorded at weekly visits. Clinical effectiveness, disability, and treatment preference were also assessed.\n Fifty patients were enrolled and 38 completed the study (16 men, 22 women, age 70+/-11 years, onset of postherpetic neuralgia 31+/-29 months, duration of pain 18+/-5 hours per day). The oxycodone dose during the final week was 45+/-17 mg per day. Compared with placebo, oxycodone resulted in pain relief (2.9+/-1.2 versus 1.8+/-1.1, p=0.0001) and reductions in steady pain (34+/-26 versus 55+/-27 mm, p=0.0001), allodynia (32+/-26 versus 50+/-30 mm, p=0.0004), and paroxysmal spontaneous pain (22+/-24 versus 42+/-32 mm, p=0.0001). Global effectiveness, disability, and masked patient preference all showed superior scores with oxycodone relative to placebo (1.8+/-1.1 versus 0.7+/-1.0, p=0.0001; 0.3+/-0.8 versus 0.7+/-1.0, p=0.041; 67% versus 11%, p=0.001, respectively).\n Controlled-release oxycodone is an effective analgesic for the management of steady pain, paroxysmal spontaneous pain, and allodynia, which frequently characterize postherpetic neuralgia.", "To investigate the effects of IV morphine on central pain syndromes through quantitative sensory testing and to assess the long-term benefit of oral morphine.\n After an initial open titration phase aiming to determine the maximal tolerated dosage of IV morphine, the efficacy of morphine infusion (9-30 mg; mean dosage, 16 mg) was assessed in a double-blind, placebo-controlled and crossover fashion in 15 patients with poststroke- (6 patients) or spinal cord injury- (9 patients) related pain. All of the patients subsequently received sustained oral morphine.\n Morphine significantly reduced the intensity of brush-induced allodynia but had no effect on other evoked pains (i.e., static mechanical and thermal allodynia/hyperalgesia). The effects of morphine on ongoing pain were not significantly different from those of the placebo, but 7 patients (46%) responded to morphine. There was a correlation between the effects of morphine on spontaneous pain and the decrease of the responses to suprathreshold thermal stimuli on the nonpainful contralateral side, suggesting that these effects were related to the general antinociceptive activity of the drug. The effects of IV morphine were correlated with those of oral morphine at 1 month, but only 3 patients (20%) were still taking morphine after 1 year.\n IV morphine induces analgesic effects on some components of central neuropathic pain syndromes, but only a minority of patients may benefit from long-term opioid treatment.", "Although opioids are commonly used to treat chronic neuropathic pain, there are limited data to guide their use. Few controlled trials have been performed, and many types of neuropathic pain remain unstudied.\n Adults with neuropathic pain that was refractory to treatment were randomly assigned to receive either high-strength (0.75-mg) or low-strength (0.15-mg) capsules of the potent mu-opioid agonist levorphanol for eight weeks under double-blind conditions. Intake was titrated by the patient to a maximum of 21 capsules of either strength per day. Outcome measures included the intensity of pain as recorded in a diary, the degree of pain relief, quality of life, psychological and cognitive function, the number of capsules taken daily, and blood levorphanol levels.\n Among the 81 patients exposed to the study drug, high-strength levorphanol capsules reduced pain by 36 percent, as compared with a 21 percent reduction in pain in the low-strength group (P=0.02). On average, patients in the high-strength group took 11.9 capsules per day (8.9 mg per day) and patients in the low-strength group took close to the 21 allowed (18.3 capsules per day; 2.7 mg per day). Affective distress and interference with functioning were reduced, and sleep was improved, but there were no differences between the high-strength group and the low-strength group in terms of these variables. Noncompletion of the study was primarily due to side effects of the opioid. Patients with central pain after stroke were the least likely to report benefit.\n The reduction in the intensity of neuropathic pain was significantly greater during treatment with higher doses of opioids than with lower doses. Higher doses produced more side effects without significant additional benefit in terms of other outcome measures.\n Copyright 2003 Massachusetts Medical Society", "We studied the analgesic efficacy of an intravenous infusion of lidocaine and morphine in 19 adults with well-established postherpetic neuralgia in a three-session, randomized, double-blind, placebo-controlled trial. Compared with saline placebo, both lidocaine and morphine reduced pain intensity. Reductions in pain did not correlate with side effects produced by the infusions. For morphine, there was a significant correlation between reductions in pain intensity and blood level achieved. In the majority of subjects who reported definite pain relief, allodynia also disappeared. The results show that neuropathic pain can respond to opioids and to systemically administered local anesthetic drugs.", "Forty-three patients with peripheral neuropathic pain, exclusively pain reduced by spinal cord stimulation (SCS), were switched into a painful state after SCS inactivation. This mode was used to assess the pain-relieving effect of carbamazepine (CMZ) and opioids in a double-blinded, placebo-controlled trial. In Phase 1, the patients were randomly allocated to receive either CMZ (600 mg/d) or placebo during an SCS-free period of 8 days. In Phase 2, after a CMZ elimination interval of 7 days, 38 patients received either sustained-release morphine (90 mg/d) or placebo for 8 days. In cases of intolerable pain, the patients were authorized to reactivate their SCS. The pain intensity was rated on a numeric analog scale. In 38 patients who completed Phase 1, significant delay in pain increase was observed in the CMZ group as compared with placebo (P = 0.038). In Phase 2, the trend observed with morphine was insignificant (P = 0.41). Two CMZ patients and one morphine patient showed complete pain relief and preferred to continue the medication. Thirty-five patients returned to SCS. We conclude that CMZ is effective in peripheral neuropathic pain. Morphine obviously requires larger individually titrated dosages than those used in this study for results to be adequately interpreted.", "In a double-blind, placebo controlled crossover study, the effect of morphine on the affective and sensory pain ratings in different forms of chronic pain was investigated. Six patients suffering from central neurogenic pain, 8 from peripheral neurogenic pain and 6 from idiopathic pain participated in the study. Morphine (0.3 mg/kg bodyweight) and placebo (saline) were administered intravenously. Both the affective and sensory dimensions of pain sensation were assessed by means of the 101-point rating scale. From our results it appeared that morphine reduced the affective but not the sensory dimension of pain sensation in both groups of neurogenic pain patients. In the idiopathic pain group, neither the affective nor the sensory dimension of pain sensation were affected. The observed differences in opioid responsiveness were neither the result of differences in opioid consumption nor of differences in baseline pain levels.", "Painful neuropathy is one of the most common long-term complications of diabetes mellitus and often proves difficult to relieve.\n Patients with diabetic neuropathy with moderate or greater pain for at least 3 months, were evaluated for efficacy, safety and health-related quality of life (QOL) while receiving controlled-release (CR) oxycodone (OxyContin) or active placebo. Patients underwent washout from all opioids 2-7 days before randomization to 10 mg CR oxycodone or active placebo (0.25 mg benztropine) q12h. The dose was increased, approximately weekly, to a maximum of 40 mg q12h CR oxycodone or 1 mg q12h benztropine, with crossover to the alternate treatment after a maximum of 4 weeks. Acetaminophen, 325-650 mg q4-6h prn was provided as rescue.\n Thirty-six patients were evaluable for efficacy (21 men, 15 women, mean age 63.0+/-9.4 years). CR oxycodone resulted in significantly lower (P=0.0001) mean daily pain (21.8+/-20.7 vs. 48.6+/-26.6 mm VAS), steady pain (23.5+/-23.0 vs. 47.6+/-30.7 mm VAS), brief pain (21.8+/-23.5 vs. 46.7+/-30.8 mm VAS), skin pain (14.3+/-20.4 vs. 43.2+/-31.3 mm VAS), and total pain and disability (16.8+/-15.6 vs. 25.2+/-16.7; P=0.004). Scores from 6 of the 8 SF-36 domains and both summary scales, Standardized Physical Component (P=0.0002) and Standardized Mental Component (P=0.0338) were significantly better during CR oxycodone treatment. The number needed to treat to obtain one patient with at least 50% pain relief is 2.6 and clinical effectiveness scores favoured treatment with CR oxycodone over placebo (P=0.0001).\n CR oxycodone is effective and safe for the management of painful diabetic neuropathy and improves QOL.", "There is controversy about whether the lack of response of some chronic pain to opioid treatment is absolute or relative. It is widely believed that nociceptive pain is responsive to opioids whereas neuropathic pain tends not to be. We have used a method of patient-controlled analgesia (PCA) with simultaneous nurse-observer measurement of analgesia, mood, and adverse effects to address these issues. Ten patients with chronic pain were given morphine at two concentrations (10 and 30 mg/ml) by PCA in two separate sessions in a double-blind randomised crossover study. Before the study a clinical judgment was made as to whether each pain was nociceptive or neuropathic. Seven patients showed good analgesic responses (more than 70 mm pain relief on a visual-analogue scale) of pain at rest, two patients poor responses (less than 30 mm pain relief), and one a moderate response with both concentrations (30-70 mm pain relief). The response to morphine was consistent (greater and faster relief with the higher concentration) in nine patients. Two patients had pain on movement that responded moderately to low-concentration morphine and well to the higher concentration. All patients with pains judged to be nociceptive showed good analgesic responses compared with half of those with neuropathic pain. There was no evidence that analgesic responses in patients with neuropathic pain were due to changes in mood. This PCA method is a quick and efficient tool to determine the consistency of the analgesic response. Such consistency can guide the clinician as to whether continued or higher-dose opioid treatment will produce good analgesia. An inconsistent response points to the use of other pain-relieving strategies.", "Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial.\n To compare the analgesic and cognitive effects of opioids with those of TCA and placebo in the treatment of PHN.\n Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks' duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication.\n Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001), with no appreciable effect on any cognitive measure. The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%; p = 0.02).\n Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.", "NMDA antagonists and opioids relieve experimentally produced hyperalgesia in animals and humans, presumably by attenuating a heightened central nervous system response to afferent input. A few small studies in patients have suggested that intravenous boluses or rapid infusions of the N-methyl-D-aspartate (NMDA) antagonist ketamine relieve some neuropathic pains but also produce disturbances of cognition and mood. In a randomized, double-blind, crossover trial, we treated eight patients with chronic posttraumatic pain and widespread mechanical allodynia with 2-h intravenous infusions of the NMDA antagonist ketamine (mean dose, 58 mg), the opioid mu-receptor agonist alfentanil (mean dose, 11 mg), and placebo. The patients were selected because extensive sensory testing suggested that altered central processing contributed to their symptoms. The slow rate of drug infusion was chosen to see if pain relief would precede dose-limiting side effects. Means of the peak effect scores achieved during the 2-h infusion were for pain relief: ketamine, 65%, alfentanil, 46%, and placebo, 22% (p < 0.01 for ketamine and p = 0.08 for alfentanil, each compared to placebo); and for relief of allodynia: ketamine, 71%, alfentanil, 57%, and placebo, 21% (p < 0.01 for both ketamine and alfentanil). Appreciable symptomatic relief developed only after the onset of unpleasant drug side effects. After the infusion was stopped, pain relief disappeared before the side effects resolved. We conclude that NMDA antagonists may have promise for the treatment of neuropathic pain, but strategies are needed to improve their therapeutic ratio, such as intrathecal administration or systemic treatment with more selective drugs.", "The aim of the present study has been to assess the responsiveness of various types of chronic pain to opioids given i.v. and tested against placebo in a double-blind, randomized fashion. Pain classified as primary nociceptive was effectively alleviated (P greater than 0.001) while neuropathic deafferentation pain was not significantly influenced by morphine or equivalent doses of other opioids. Also 'idiopathic' pain, defined as chronic pain with no or little demonstrable pathology, failed to respond. The results were not related to whether the patients were regular users of narcotic analgesics or not. The outcome of our double-blind opioid test has proved useful to justify a continued, or discontinued, use of narcotic medication in individual patients. It may also support the indication and choice of invasive stimulation procedures (spinal cord or brain). The results of the study illustrate the misconception of chronic pain as an entity and highlight the importance of recognizing different neurobiological mechanisms and differences in responsiveness to analgesic drugs as well as to non-pharmacological modes of treatment. The opioid test has thus become a valuable tool in pain analysis and helpful as a guide for further treatment." ]

[ "3243609", "3623260", "3755517", "3488384" ]

[ "Effect of vitamin D supplementation during pregnancy on foetal growth.", "Effect of calcium and vitamin D supplementation on toxaemia of pregnancy.", "Vitamin D supplementation in pregnancy: a controlled trial of two methods.", "Vitamin D supplementation during pregnancy: effect on neonatal calcium homeostasis." ]

[ "nan", "To study the effect of calcium and vitamin D supplementation on the incidence of toxaemia of pregnancy, 200 randomly selected pregnant women (supplemented group), were put on calcium (375 mg/day) and vitamin D (1,200 IU/day) supplements at 20-24 weeks of pregnancy onwards. Another 200 pregnant women constituted the non-supplemented group. At 32 and 36 weeks of pregnancy the systolic and diastolic blood pressure of non-toxemic women was significantly lower in the supplemented group than in the non-supplemented group. However, the incidence of toxaemia in the supplemented group (6%) was not significantly different from that in the non-supplemented group (9%).", "A randomized study was conducted to evaluate the effects of single-dose and daily vitamin D supplementation in pregnant women during the last trimester of a winter pregnancy in the Northwest of France. The women were divided into three randomized groups: one (N = 21) was given a vitamin D2 supplement of 1000 IU/day during the last three months of pregnancy, one (N = 27) was given a single oral dose of 5 mg at the seventh month of pregnancy, and one (N = 29) acted as a control. Venous plasma samples were obtained at delivery from the women and from cord blood, and levels of calcium, 25-OHD, and 1,25(OH)2D were determined. No significant difference in plasma calcium concentration was found among the three groups, but within each group plasma calcium concentrations were higher in the cord samples than in the respective maternal samples. The levels of the two metabolites measured were consistently lower in the cord samples than in the respective maternal samples. Cord 25-OHD concentrations correlated with those of maternal plasma. No significant modification of maternal calciuria or of the birth weight of term infants was observed. 25-OHD concentrations were greater in maternal and cord plasma from treated mothers, but only a slight difference was observed between the supplemented groups. 1,25(OH)2D concentrations were not significantly different in the three groups. A single 5-mg dose of vitamin D given orally at the seventh month of pregnancy provides effective prophylaxis in the authors' region.", "We assessed whether modification of vitamin D nutritional status during the last trimester of pregnancy affects maternal and neonatal calcium homeostasis. At the end of the first trimester, 40 pregnant women were randomly assigned to either of two groups, and blood taken to assess the basal values of Ca, Pi, Mg, iPTH, 25-OHD, and 1,25(OH)2D. From the sixth month on, group 1 (+D) received 1000 IU vitamin D3 daily; group 2 (-D) served as control. At the time of delivery, maternal serum 25-OHD was higher in the +D group (P less than 0.0005). Ca, Pi, iPTH, and 1,25(OH)2D were not affected. At term, venous cord 25-OHD levels were also higher in the +D group (P less than 0.0005), and 1,25(OH)2D levels slightly lower (P less than 0.05), but neither Ca, Pi, nor iPTH differed between the two groups. Serum CaT dropped significantly (P less than 0.002) at 4 days of age in the infants from both groups, although to a lesser extent in these from the +D group (P less than 0.05). Circulating iPTH increased in both groups. Serum 25-OHD remained low in the -D group, and dropped slightly in the +D group; 1,25(OH)2D remained stable during the first 4 days of life in the -D group, and increased in the +D group (P less than 0.001). Our data demonstrate the importance of providing adequate maternal vitamin D stores to ensure better perinatal handling of calcium. This is of particular importance for populations at risk for hypovitaminosis D." ]

[ "10601063", "2643038" ]

[ "Manometry based randomised trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction.", "The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with sphincter-of-Oddi dysfunction." ]

[ "Endoscopic sphincterotomy for biliary-type pain after cholecystectomy remains controversial despite evidence of efficacy in some patients with a high sphincter of Oddi (SO) basal pressure (SO stenosis).\n To evaluate the effects of sphincterotomy in patients randomised on the basis of results from endoscopic biliary manometry.\n Endoscopic biliary manometry was performed in 81 patients with biliary-type pain after cholecystectomy who had a dilated bile duct on retrograde cholangiography, transient increases in liver enzymes after episodes of pain, or positive responses to challenge with morphine/neostigmine. The manometric record was categorised as SO stenosis, SO dyskinesia, or normal, after which the patient was randomised in each category to sphincterotomy or to a sham procedure in a prospective double blind study. Symptoms were assessed at intervals of three months for 24 months by an independent observer, and the effects of sphincterotomy on sphincter function were monitored by repeat manometry after three and 24 months.\n In the SO stenosis group, symptoms improved in 11 of 13 patients treated by sphincterotomy and in five of 13 subjected to a sham procedure (p = 0.041). When manometric records were categorised as dyskinesia or normal, results from sphincterotomy and sham procedures did not differ. Complications were rare, but included mild pancreatitis in seven patients (14 episodes) and a collection in the right upper quadrant, presumably related to a minor perforation. At three months, the endoscopic incision was extended in 19 patients because of manometric evidence of incomplete division of the sphincter.\n In patients with presumed SO dysfunction, endoscopic sphincterotomy is helpful in those with manometric features of SO stenosis.", "Forty-seven patients thought to have dysfunction of the sphincter of Oddi were randomly assigned to undergo endoscopic sphincterotomy or sham sphincterotomy in a prospective double-blind study. All the patients had pain resembling biliary pain, had previously undergone a cholecystectomy, and had clinical characteristics suggesting biliary obstruction. The patients were randomly assigned to the treatment (n = 23) or nontreatment (n = 24) group before manometric examination of the sphincter of Oddi was performed. Sphincterotomy resulted in improvement in pain scores at one-year follow-up in 10 of 11 patients with elevated sphincter pressure. In contrast, there was improvement in only 3 of 12 patients with elevated basal sphincter pressures who underwent the sham procedure. In patients with normal sphincter pressure, pain scores were similar regardless of treatment. After one year, sphincterotomy was performed in 12 symptomatic patients who had undergone the sham procedure--7 with elevated sphincter pressures and 5 with normal sphincter pressures. Forty patients were followed for four years. Of the 23 patients with increased sphincter pressure, 10 of the original 11 who underwent sphincterotomy remained virtually free of pain; 7 others who subsequently underwent sphincterotomy also benefited from it. Thus, 17 of 18 patients with sphincter-of-Oddi dysfunction verified by manometry benefited from sphincterotomy. In patients with normal sphincter pressure, sphincterotomy was no more beneficial than sham therapy. Our observations suggest that endoscopic sphincterotomy offers long-term relief of pain in a group of patients with verified sphincter-of-Oddi dysfunction." ]

[ "20599196", "16678826" ]

[ "Uterine massage to reduce postpartum hemorrhage after vaginal delivery.", "Uterine massage and postpartum blood loss." ]

[ "To determine the effectiveness of sustained uterine massage started before delivery of the placenta in reducing postpartum hemorrhage.\n A randomized controlled trial conducted in Egypt and South Africa between September 2006 and February 2009. A total of 1964 pregnant women were randomly allocated to 1 of 3 treatment groups: intramuscular oxytocin, sustained uterine massage, or both treatments. Blood loss within 30 minutes of delivery was recorded.\n The incidence of blood loss of 300 mL or more within 30 minutes of delivery was significantly higher in the massage group than in the massage plus oxytocin (RR 1.88; 95% CI, 1.29-2.74 in Assiut, and RR 1.3; 95% CI, 1.00-1.68 in SA) and the oxytocin only group (RR 1.7; 95% CI, 1.11-2.61 in Assiut, and RR 2.24; 95% CI, 1.54-3.27 in SA). In both centers, use of additional uterotonics was significantly higher in the uterine massage group compared with the other 2 groups.\n Uterine massage was less effective than oxytocin for reducing blood loss after delivery. When oxytocin was used, there was no additional benefit from uterine massage. The effectiveness of uterine massage in the absence of oxytocin was not studied. ACTRN: 12609000372280.\n Copyright © 2010 International Federation of Gynecology and Obstetics. Published by Elsevier Ireland Ltd. All rights reserved.", "nan" ]

[ "12241833", "16401473", "8535807", "9687996", "8598755" ]

[ "Wait-and-see policy or laparoscopic cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a randomised trial.", "Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients.", "Long-term follow-up of a prospective randomized study of endoscopic versus surgical treatment of bile duct calculi in patients with gallbladder in situ.", "Surgery vs endoscopy as primary treatment in symptomatic patients with suspected common bile duct stones: a multicenter randomized trial. French Associations for Surgical Research.", "Randomised trial of endoscopic sphincterotomy with gallbladder left in situ versus open surgery for common bileduct calculi in high-risk patients." ]

[ "Patients who undergo endoscopic sphincterotomy for common bile-duct stones, who have residual gallbladder stones, are referred for laparoscopic cholecystectomy. However, only 10% of patients who do not have this operation are reported to develop recurrent biliary symptoms. We aimed to assess whether a wait-and-see policy is justified.\n We did a prospective, randomised, multicentre trial in 120 patients (age 18-80 years) who underwent endoscopic sphincterotomy and stone extraction, with proven gallbladder stones. Patients were randomly allocated to wait and see (n=64) or laparoscopic cholecystectomy (56). Primary outcome was recurrence of at least one biliary event during 2-year follow-up, and secondary outcomes were complications of cholecystectomy and quality of life. Analysis was by intention to treat.\n 12 patients were lost to follow-up immediately. Of 59 patients allocated to wait and see, 27 (47%) had recurrent biliary symptoms compared with one (2%) of 49 patients after laparoscopic cholecystectomy (relative risk 22.42, 95% CI 3.16-159.14, p<0.0001). 22 (81%) of 27 patients underwent cholecystectomy, mainly for biliary pain (n=13) or acute cholecystitis (7). Conversion rate to open surgery was 55% in patients allocated to wait and see who underwent cholecystectomy compared with 23% in those who were allocated laparoscopic cholecystectomy (p=0.0104). Morbidity was 32% versus 14% (p=0.1048), and median hospital stay was 9 versus 7 days. Quality of life returned to normal within 3 months after either treatment policy.\n A wait-and-see policy after endoscopic sphincterotomy in combined cholecystodocholithiasis cannot be recommended as standard treatment, since 47% of expectantly managed patients developed at least one recurrent biliary event and 37% needed cholecystectomy. No major biliary complications arose, but conversion rate was high.", "In patients with stones in their bile ducts and gallbladders, cholecystectomy is generally recommended after endoscopic sphincterotomy and clearance of bile duct stones. However, only approximately 10% of patients with gallbladders left in situ will return with further biliary complications. Expectant management is alternately advocated. In this study, we compared the treatment strategies of laparoscopic cholecystectomy and gallbladders left in situ.\n We randomized patients (>60 years of age) after endoscopic sphincterotomy and clearance of their bile duct stones to receive early laparoscopic cholecystectomy or expectant management. The primary outcome was further biliary complications. Other outcome measures included adverse events after cholecystectomy and late deaths from all causes.\n One hundred seventy-eight patients entered into the trial (89 in each group); 82 of 89 patients who were randomized to receive laparoscopic cholecystectomy underwent the procedure. Conversion to open surgery was needed in 16 of 82 patients (20%). Postoperative complications occurred in 8 patients (9%). Analysis was by intention to treat. With a median follow-up of approximately 5 years, 6 patients (7%) in the cholecystectomy group returned with further biliary events (cholangitis, n = 5; biliary pain, n = 1). Among those with gallbladders in situ, 21 (24%) returned with further biliary events (cholangitis, n = 13; acute cholecystitis, n = 5; biliary pain, n = 2; and jaundice, n = 1; log rank, P = .001). Late deaths were similar between groups (cholecystectomy, n = 19; gallbladder in situ, n = 11; P = .12).\n In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.", "Eighty-three patients with bile duct calculi were entered in a prospective randomized study of endoscopic sphincterotomy (ES) and stone removal (group 1) versus surgery alone (group 2), and were followed for more than 5 years. In group 1 endoscopic stone clearance was successful in 35 of 39 patients. Thirteen patients subsequently had cholecystectomy with (n = 7) or without (n = 6) biliary symptoms and one had a cholecystostomy for acute cholecystitis. Two patients have had mild biliary colic or pancreatitis. Two patients died from gallbladder carcinoma after 9 days and 18 months. In group 2 bile duct stones were cleared surgically in 37 of 41 patients. Late complications occurred in two patients (incisional hernia and recurrent stone). One patient with gallbladder carcinoma was cured and another died after 16 months. Early major and minor complications occurred in three and four respectively of 39 patients in group 1, and in three and six respectively of 41 patients in group 2. There were no deaths. During follow-up the total morbidity rate reached 28 percent (11 of 39) and 5 percent (two of 41) (P = 0.005) and the non-biliary related mortality rate was 31 percent (12 of 39) and 10 percent (four of 41) (P = 0.02) in groups 1 and 2 respectively. Nine patients in group 1 and two in group 2 died from heart disease (P = 0.02). Total hospital stay was 2-42 (median 13) days and 6-36 (median 16) days in groups 1 and 2 respectively (P not significant). Endoscopic and surgical treatment of bile duct calculi in middle-aged and elderly patients with gallbladder in situ are equally effective in the long term. However, the significantly increased mortality rate from heart disease in patients treated endoscopically compared with those treated surgically might speak in favour of operation.", "To compare surgical treatment (ST) with endoscopic management (EM) in patients with suspected common bile duct stones.\n Two hundred twenty eligible patients originating from 18 surgery units. Patients enrolled in this multicenter randomized study had clinical symptoms that included jaundice, mild pancreatitis (Ranson score < or = 2), or mild acute cholangitis; biliary colic (with increased alkaline phosphatase levels); and common bile duct stones or a common bile duct diameter of 1 cm or larger on ultrasonography.\n Two hundred two patients were randomly assigned to either ST (n=105) or EM (n=97) during a 5-year period. Both groups were comparable with respect to age, sex, American Society of Anesthesiologists score, and clinical presentation.\n The rates of early postoperative additional procedures necessary to deal with the impossibility to perform the initial procedure, complications, and retained stones after ST or EM. Subsidiary endpoints were intention-to-treat analyses of mortality and of major complications and the duration of hospital stay.\n Surgical treatment was associated with a significantly (P<.001) lower rate of 1 or 2 additional procedures (8% vs 29%) due to a significantly lower rate of the impossibility to perform the initial procedure (0% vs 5%) (P<.05), major complications (4% vs 13%) (P<.05), and retained stones (6% vs 16%) (P<.04). Minor complications occurred more often in patients having ST (4%) than in those having EM (0%) (P<.01). Cholecystectomy was performed routinely in 102 patients having ST and electively in 36 patients having EM. There was 1 death in each group initially. On an intention-to-treat analysis, 3 deaths (3.1%) occurred after EM and 1 (0.9%) after ST; this difference was not statistically significant (P=.56). Major complications occurred in 4% of patients having ST compared with 1 1% of patients having EM (P<.002). The median duration of hospital stay was 16 days in patients having ST and 12 days in those having EM; this difference was not statistically significant (P=.09).\n Whether an additional cholecystectomy is performed routinely or electively, the high risk of additional procedures after EM precludes its use as the optimal therapy in patients with symptomatic common bile duct stones, except in those with severe cholangitis.", "Morbidity and mortality after surgical treatment of bileduct stones increase with age and associated diseases. A proposed alternative therapy is endoscopic sphincterotomy (ES) with the gallbladder left in situ, and we elected to compare this option with standard open surgery in high-risk patients.\n 98 patients (mean age 80 years) with symptoms likely to be due to bileduct stones or a recent episode of biliary pancreatitis were randomised to be treated either by open cholecystectomy with operative cholangiography and (if necessary) bileduct exploration (n=48) or by endoscopic sphincterotomy alone (n=50).\n The procedure was accomplished successfully in 94% of the surgery group and 88% of the ES group, and there were no significant differences in immediate morbidity (23% vs 16%) or mortality (4% vs 6%). During mean follow-up of 17 months biliary symptoms recurred in three surgical patients, none of whom underwent repeat surgery, and in 10 ES patients, seven of whom had biliary surgery. By multivariate regression analysis endoscopic sphincterotomy was an independent predictor of recurrent biliary symptoms (odds ratio 6.9; 95% Cl 1.46 to 32.54).\n In elderly or high-risk patients, surgery is preferable to endoscopic sphincterotomy with the gallbladder left in situ as a definitive treatment for bileduct stones or non-severe biliary pancreatitis." ]

[ "1986079", "10910540", "12091845" ]

[ "Glucose and insulin versus cation-exchange resin for the treatment of hyperkalemia in very low birth weight infants.", "Glucose and insulin infusion versus kayexalate for the early treatment of non-oliguric hyperkalemia in very-low-birth-weight infants.", "Efficacy of albuterol inhalation in treatment of hyperkalemia in premature neonates." ]

[ "nan", "Forty very low birth weight (VLBW) infants with non-oliguric hyperkalemia in the first few days after birth were enrolled in this study. They were randomly divided into 2 groups, regular insulin (RI) infusion group and kayexalate resin enema group. Therapy was administered when serum potassium level was greater than 6 mEq/L. None of these infants received blood transfusion during this study course. In RI group (n = 20), the ratio of infusion glucose to regular insulin was 10-15 gm glucose to 1 unit RI, and the glucose infusion rate was maintained at least 6 mg/Kg/min. In Kayexalate group (n = 20), the dose of Kayexalate was 1 gm/Kg body weight given rectally every four hours. All treatment discontinued after the serum potassium level returned to normal for 6 hours. The mean gestational ages were 27.4 +/- 1.8 weeks in RI group and 28.4 +/- 2.4 weeks in Kayexalate group, respectively. Mean birth weights were 935 +/- 259 gm (RI) and 1065 +/- 214 gm (Kayexalate). The ages at onset of hyperkalemia were 24.6 +/- 8.2 (RI) and 22.2 +/- 8.1 (Kayexalate) hours after birth. The mean urine outputs during the 8-hour interval prior to development of hyperkalemia were 5.4 +/- 1.3 (RI) and 5.5 +/- 0.9 (Kayexalate) ml/kg/min. The durations of hyperkalemia were 26.4 +/- 14.9 (RI) and 38.6 +/- 13.3 (Kayexalate) hours. The peak serum potassium levels during therapy were 7.3 +/- 0.9 and 7.4 +/- 0.6 mEq/L. The incidences of grade II and above intraventricular hemorrhage (IVH) were 15% (3/20) and 50% (10/20). The incidences of cardiac dysrhythmia were 5% (1/20) and 10% (2/20). Significantly shorter duration of non-oliguric hyperkalemia and lower incidence of IVH were noted in RI group, but there were no differences in the peak potassium level or the incidence of cardiac dysrhythmia between these two groups. We conclude that to use early continuous regular insulin infusion therapy for the treatment of non-oliguric hyperkalemia in VLBW infants is more effective than kayexalate in decreasing the duration of hyperkalemia and reducing the incidence of intraventricular hemorrhage.", "To evaluate the efficacy of inhaled albuterol for treatment of hyperkalemia in premature neonates by conducting a prospective, randomized placebo-controlled and double-blinded clinical trial.\n Neonates <2000 g receiving mechanical ventilation with central serum potassium > or =6.0 mmol/L (6.0 mEq/L), were randomly assigned to treatment or placebo groups. Albuterol (400 microg) or saline was given by nebulization. The dose was repeated every 2 hours until the potassium level fell below 5 mmol/L (maximum 12 doses) or there were signs of toxicity.\n Nineteen patients completed the study (8 in the albuterol and 11 in the saline group). Serum potassium levels declined rapidly in the first 4 hours in the albuterol group, from 7.06 +/- 0.23 mmol/L to 6.34 +/- 0.24 mmol/L (P =.003) versus no significant change in the saline group (6.88 +/- 0.18 mmol/L to 6.85 +/- 0.24 mmol/L; P =.87). At 8 hours, the fall continued to be greater in the albuterol group versus the saline group (5.93 +/- 0.3 mmol/L and 6.35 +/- 0.22 mmol/L, respectively; P =.04).\n Albuterol inhalation may be useful in rapidly lowering serum potassium levels in premature neonates." ]

[ "10831024", "10440457", "3117156", "9754845", "12496955" ]

[ "Randomized, placebo-controlled pilot study of divalproex sodium in the treatment of acute exacerbations of chronic schizophrenia.", "Effects of carbamazepine and valproate on haloperidol plasma levels and on psychopathologic outcome in schizophrenic patients.", "The effect of sodium valproate on tardive dyskinesia--revisited.", "Combined treatment of schizophrenic psychoses with haloperidol and valproate.", "Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia." ]

[ "Experimental and clinical data suggest that GABA-ergic drugs such as valproate may have a potential role in the treatment of schizophrenia. The authors designed a 21-day prospective, double-blind, randomized, placebo-controlled pilot study of divalproex sodium as add-on treatment to haloperidol in 12 hospitalized patients with acute exacerbations of chronic schizophrenia. All patients received haloperidol 10 mg/day for 3 days and 15 mg/day for the remaining 18 days. In addition, five patients were randomly assigned to receive divalproex augmentation and seven to receive placebo. The divalproex dose was adjusted to a target serum concentration of 75 microg/mL for 2 weeks; placebo replaced divalproex during the third and last weeks to determine any carryover effect. Psychiatric rating scales were administered at baseline and on days 7, 14, and 21. Although the placebo group improved with haloperidol treatment, the divalproex group demonstrated greater improvement. On day 21, the divalproex group had greater improvement from baseline on the Clinical Global Impression Scale (p < or = 0.04), Brief Psychiatric Rating Scale (p < or = 0.13), and Schedule for Assessment of Negative Symptoms scores (p < or = 0.007). After divalproex withdrawal on day 15, a carryover effect was observed during week 3. The authors concluded that the addition of divalproex sodium to standard antipsychotic drugs may prove effective in relieving the symptoms of acute schizophrenia. Future studies may benefit from the design of this pilot study. However, it is premature to apply this augmentation strategy in the clinical setting just yet because of the small sample size and the likely heterogeneity of the disorder.", "The objective of this study was to compare the effects of carbamazepine (CBZ) and valproate (VPA) cotreatment on the plasma levels of haloperidol and on the psychopathologic outcome in schizophrenic disorders. In this controlled clinical trial, 27 patients with an ICD-10 diagnosis of schizophrenia (N = 24) or schizoaffective disorder (N = 3) were randomly assigned to receive 4 weeks of treatment with either haloperidol alone, haloperidol with CBZ, or haloperidol with VPA. Whereas the haloperidol dose remained stable, the antiepileptic drug doses were adjusted to achieve therapeutic plasma levels. Clinical state was rated by the Positive subscale of the Positive and Negative Syndrome Scale and the Inpatient Multidimensional Psychiatric Scale. The use of CBZ was associated with significantly lower haloperidol plasma levels and with a worse clinical outcome compared with antipsychotic monotherapy. VPA had no significant effect on either plasma levels or on psychopathology. Our results suggest that comedication with haloperidol and CBZ is associated with a high risk for treatment failure. This might be a result of a pharmacokinetic interaction on the hepatic level. The concomitant use of VPA with neuroleptic therapy is not impaired by clinically significant drug interactions, but it is not associated with a better outcome under our conditions.", "As a treatment for tardive dyskinesia, sodium valproate was tested in a double-blind placebo-controlled parallel group trial, with 6-week base-line observation period followed by 6 weeks of treatment. Sodium valproate was not found to be an effective treatment for either tardive dyskinesia or drug-induced Parkinsonism, and did not affect mental state or behaviour.", "In accordance with a previous study of adjuvant effects of the anticonvulsant carbamazepine (CBZ) on the neuroleptic treatment of schizophrenic psychoses, the effects of valproate (VPA) were tested in a randomly assigned double-blind, placebo-controlled study. Apart from a (statistically nonsignificant) psychopathological deterioration following discontinuation of VPA while on continuous neuroleptic mediation after four weeks and a statistically significant effect on \"hostile belligerence\", no overall therapeutic effects of the combination of haloperidol (HPD) with VPA were observed under controlled conditions. Unlike the results with CBZ, concomitant use of VPA led to an even higher consumption of haloperidol and biperiden and to a higher rate of extrapyramidal symptoms compared with the corresponding placebo group, although these differences did not attain statistical significance. In regard to use of the sedative neuroleptic chlorprothixene, there was a trend toward lower doses in the VPA group than in the placebo group. From these results, adjuvant effects like those of carbamazepine in the neuroleptic treatment of schizophrenic psychoses could not be confirmed for valproate in the present study. However, the trend toward lower doses of sedative medication and observed effects on \"hostile belligerence\" may indicate sedative and/or antimanic properties of valproate which have recently been demonstrated in several controlled studies.", "This double-blind, randomized, multicenter study investigated the use of divalproex with an antipsychotic agent in patients hospitalized for acute exacerbation of schizophrenia. Patients (n = 249) who met DSM-IV criteria for schizophrenia were randomly assigned to receive olanzapine monotherapy, risperidone monotherapy, divalproex plus olanzapine, or divalproex plus risperidone for 28 days. Divalproex was initiated at 15 mg/kg/day and titrated over 12 days to a maximum dosage of 30 mg/kg/day. Olanzapine and risperidone, were, respectively, initiated at 5 and 2 mg/day and were titrated over the first 6 days to respective target fixed daily dosages of 15 and 6 mg/day. Improvements from baseline were observed at all evaluation points throughout the 28-day treatment period in the two combination therapy and the two antipsychotic monotherapy groups, with statistically significant treatment differences favoring combination therapy as soon as day 3 for Positive and Negative Syndrome Scale (PANSS) total score, derived Brief Psychiatric Rating Scale (BPRSd) total score, as well as PANSS and BPRSd subscales. These findings were confirmed in post hoc repeated-measures analyses of variance in which treatment differences favoring combination therapy were observed for PANSS total (p = 0.020) and PANSS positive scale scores (p = 0.002). Both combination therapy and antipsychotic monotherapy were well tolerated. Treatment with divalproex in combination with an atypical antipsychotic agent resulted in earlier improvements in a range of psychotic symptoms among acutely hospitalized patients with schizophrenia. Further evaluation is warranted to confirm these findings." ]

[ "16130206", "14560224", "19118733" ]

[ "Comparison of surveillance vs Aortic Endografting for Small Aneurysm Repair (CAESAR) trial: study design and progress.", "Quality of life, impotence, and activity level in a randomized trial of immediate repair versus surveillance of small abdominal aortic aneurysm.", "Fit patients with small abdominal aortic aneurysms (AAAs) do not benefit from early intervention." ]

[ "The CAESAR Trial aims to assess the outcome of endovascular repair (EVAR) vs surveillance of small abdominal aortic aneurysms (AAA) with maximum diameter of 4.1-5.4 cm on computerised tomography (CT) scan.\n Patients between 50 and 80 years of age, with small AAA, anatomically suitable for EVAR, are randomly allocated to early EVAR or surveillance. The primary outcome measure is survival. Secondary endpoints include: aneurysm-related deaths (defined as any death caused directly or indirectly by rupture or endovascular/open aneurysm repair), AAA rupture, peri-operative or late complications, conversion to open repair, complications associated with delayed treatment including loss of treatment options, AAA growth rates and quality of life. Target recruitment is 740 patients to show that early EVAR is associated with a 15% survival benefit at 54 months.\n Randomization started in September 2004. By the end of April 2005, 86 patients had been enrolled by 10 active European centres. Completion of recruitment is expected for September 2006 and publication of the results in mid 2007.", "We compared long-term health-related quality-of-life outcome after randomization to immediate elective repair or imaging surveillance, and in relation to time of elective repair, in patients with small asymptomatic abdominal aortic aneurysm (AAA).\n This randomized clinical trial was carried out in 16 Veterans Affairs medical centers. Study subjects were patients at good surgical risk, aged 50 to 79 years, with AAAs 4.0 to 5.4 cm in diameter. Interventions included immediate open surgical AAA repair or imaging surveillance every 6 months with repair reserved for AAAs that became symptomatic or enlarged to 5.5 cm. Main outcome measures considered were SF-36 health status questionnaire, prevalence of impotence, and maximum activity level, which were determined at randomization and at all follow-up visits.\n Eleven hundred thirty-six patients were randomized and followed up for 3.5 to 8 years (mean, 4.9 years). The two randomized groups did not differ significantly for most SF-36 scales at most times, but the immediate repair group scored higher overall in general health (P <.0001), which was particularly evident in the first 2 years after randomization, and slightly lower in vitality (P <.05). The baseline value of one SF-36 scale, physical functioning, was an independent predictor of mortality. Overall, more patients became impotent after randomization to immediate repair compared with surveillance (P <.03), but this difference did not become apparent until more than 1 year after randomization. Maximum activity level did not differ significantly between the two randomized groups, but decline over time was significantly greater in the immediate repair group (P <.02).\n For most quality-of-life measures and times there was no difference between randomized groups. Immediate repair resulted in a higher prevalence of impotence more than 1 year after randomization, but was also associated with improved perception of general health in the first 2 years.", "The UK Small Aneurysm Trial (UKSAT) and the American Aneurysm Detection and Management (ADAM) trial both concluded that early elective open surgery does not confer any late survival advantage in patients with small abdominal aortic aneurysm (AAA) with diameter 4.0 to 5.5 cm. However, two trials of endovascular aneurysm repair in small AAA have started based upon speculation that a sub-group of particularly fit patients, with low operative mortality, may benefit from early intervention. Here we investigate whether the fittest patients from the UKSAT might have benefited from early intervention.\n A total of 1090 patients randomized into the UKSAT between 1991 and 1995 were followed for an average of 12 years for mortality. Baseline data were used to calculate the Customized Probability Index (CPI), a validated prognostic risk score for operative mortality after elective open aneurysm repair that assigns risk points for history of cardiac, pulmonary, and renal disease and subtracts risk points for use of statins and beta-blockers. Cox regression was used to assess any differences in all-cause or aneurysm-related mortality between policies of early surgery or surveillance across the fitness spectrum. Tests for interaction used CPI scores as a continuous variable but patients also were stratified into tertile groups for descriptive purposes. Hazard ratios were adjusted for age, gender, and aneurysm diameter.\n A total of 714 deaths (95 aneurysm-related) occurred in 8485 person-years (number of patients multiplied by average years of conditional follow-up). The mean (standard deviation [SD]) CPI score was 8.1 (9.9) with similar scores between randomized groups. The tertile groups had mean (SD) scores of -1.8 (3.7) for the 389 fittest patients, 8.8 (3.3) for the 438 moderately fit, 21.4 (6.6) for the 261 least fit with missing scores in 2 patients. The tests for interaction were non-significant for both all-cause (P = .176) and aneurysm-related mortality (.178). However, for the least fit patients a survival advantage was seen in the early surgery group; adjusted hazard ratios 0.73 (95% confidence interval [CI] 0.56-0.96) and 0.46 (95% CI 0.22-0.98) for all-cause and aneurysm-related mortality respectively.\n Early elective surgery did not confer any survival benefit in the fittest patients. On the contrary, the possibility of a survival benefit from early intervention in patients of poor fitness merits further investigation through meta-analysis or validation in other prospective studies." ]

[ "2972171", "2972167", "2142109" ]

[ "Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery.", "Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis.", "Placebo-controlled comparison of hormonal and biochemical effects of danazol and high-dose medroxyprogesterone acetate." ]

[ "To evaluate the clinical value of postoperative hormone therapy in endometriosis, 60 patients with advanced disease were randomized to receive in a double-blind study danazol (200 mg, 3 times daily), medroxyprogesterone acetate (MPA) (100 mg daily) or placebo post-operatively for 6 months. Treatment efficacy was evaluated clinically and at laparoscopy 6 months after medication. In relation to placebo, danazol and high-dose MPA treatments, which did not differ from each other in efficacy, significantly alleviated pelvic pain. In addition, the peritoneal endometriosis lesions found at 6-months laparoscopy were significantly smaller in the MPA and danazol groups than in the placebo group. Breakthrough bleeding, weight gain and acne complicated danazol treatment but only breakthrough bleeding complicated MPA treatment. These data suggest that postoperative treatment of advanced endometriosis with high-dose MPA or danazol is clinically beneficial.", "A prospective, double-blind, placebo-controlled study was designed to evaluate the clinical efficacy and tolerance of danazol and high-dose medroxyprogesterone acetate (MPA) in the treatment of mild-moderate endometriosis. After laparoscopical confirmation of endometriosis, 59 patients were randomized to receive danazol (200 mg 3 times daily), MPA (100 mg daily) or placebo for 6 months. Clinical examinations were done before and 1, 3, 6 and 12 months after the beginning of the study, and a 2nd laparoscopy 6 months after termination of the medication. Eighteen patients in the danazol group, 16 in the MPA group and 17 in the placebo group completed the trial. Total or partial resolution of peritoneal implants was observed in 60% of the patients receiving danazol and in 63% of the patients receiving MPA. In the placebo group, resolution was observed in 18%, while the size of the implants was estimated to be increased in 23% of the patients. In relation to placebo, danazol and MPA significantly alleviated endometriosis-associated pelvic pain, lower back pain and defecation pain, but they did not differ from each other in these actions. The appearance of acne, muscle cramps, edema, weight gain and spotting bleeding complicated MPA treatment. The present results indicate that because of good efficacy and tolerance, high-dose MPA is a useful alternative in the hormonal treatment of endometriosis.", "The hormonal and biochemical effects of danazol (600 mg a day) and high-dose medroxyprogesterone acetate (MPA; 100 mg a day) were studied in a placebo-controlled, 6-month trial. Serum gonadotrophins and prolactin levels did not change during danazol and MPA treatments, whereas oestradiol and progesterone levels decreased significantly in relation to placebo without any difference between danazol and MPA. Both drugs significantly suppressed the sex hormone-binding globulin level (SHBG), and consequently, the free-androgen index (serum total testosterone nmol/l per SHBG nmol/l x 100) as compared with placebo, the effect of danazol being significantly stronger than that of MPA. Danazol, but not MPA, significantly increased serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and haemoglobin levels, and also thrombocyte counts, whereas MPA, but not danazol, increased the serum concentration of albumin in relation to placebo. Serum total bilirubin, conjugated bilirubin, gamma-glutamyl transferase, creatinine, alkaline phosphatase, sodium and potassium levels and leucocyte counts remained unchanged during both treatments. Danazol and high-dose MPA did not differ from each other in their ovarian and anterior pituitary effects, while the increase in androgenic activity induced by danazol was greater than that achieved with MPA. Danazol also had more biochemical effects than MPA. It interfered with the functions of the liver and the production of thrombocytes and haemoglobin, whereas MPA affected only albumin synthesis/release." ]

[ "12590877", "12510415", "18951261", "11929492", "17140647", "12053590", "17623754", "11256554", "10856145", "15808118", "11799368", "15829533", "17204725", "15347371", "12604023", "12670780", "16387583", "15922697", "15939317", "15305946", "17046300", "15612964", "16126052", "17507702", "12106618", "16061590", "11485708", "15647042", "10588598", "17426207", "18647656", "12570120", "11530030", "12412675", "15994387", "11240946", "15681495", "12464949", "10075616", "14682413", "17983871", "15696076", "20001651", "18430318", "11759189", "11101185", "17980416", "19544166" ]

[ "Effectiveness of montelukast versus budesonide on quality of life and bronchial reactivity in subjects with mild-persistent asthma.", "[Effectiveness and safety of montelukast versus budesonide at various doses on bronchial reactivity in subjects with mild persistent asthma].", "Deterioration in asthma control when subjects receiving fluticasone propionate/salmeterol 100/50 mcg Diskus are \"stepped-down\".", "A randomized, double-blind trial of the effect of glucocorticoid, antileukotriene and beta-agonist treatment on IL-10 serum levels in children with asthma.", "Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial.", "[Effect of triamcinolone acetonide, montelukast, nedocromil sodium and formoterol on eosinophil blood counts, ECP serum levels and clinical progression of asthma in children].", "Montelukast vs. inhaled low-dose budesonide as monotherapy in the treatment of mild persistent asthma: a randomized double blind controlled trial.", "Effects of pranlukast, a leukotriene receptor antagonist, on airway inflammation in mild asthmatics.", "Low-dose inhaled fluticasone propionate versus oral zafirlukast in the treatment of persistent asthma.", "The effect of montelukast on eosinophil apoptosis: induced sputum findings of patients with mild persistent asthma.", "Comparative efficacy and anti-inflammatory profile of once-daily therapy with leukotriene antagonist or low-dose inhaled corticosteroid in patients with mild persistent asthma.", "Daily versus as-needed corticosteroids for mild persistent asthma.", "Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma.", "Effect of montelukast compared with inhaled fluticasone on airway inflammation.", "Zafirlukast versus budesonide on bronchial reactivity in subjects with mild-persistent asthma.", "Comparison of montelukast and budesonide on bronchial reactivity in subjects with mild-moderate persistent asthma.", "Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma.", "Short-term and long-term asthma control in patients with mild persistent asthma receiving montelukast or fluticasone: a randomized controlled trial.", "The effect of montelukast and different doses of budesonide on IgE serum levels and clinical parameters in children with newly diagnosed asthma.", "Comparative effect of triamcinolone, nedocromil and montelukast on asthma control in children: A randomized pragmatic study.", "A randomized, double-blind trial of the effect of anti-asthma treatment on lung function in children with asthma.", "Effects of different anti-asthmatic agents on induced sputum and eosinophil cationic protein in mild asthmatics.", "Comparative efficacy and safety of low-dose fluticasone propionate and montelukast in children with persistent asthma.", "Randomized comparison of strategies for reducing treatment in mild persistent asthma.", "Efficacy and safety of low-dose fluticasone propionate compared with zafirlukast in patients with persistent asthma.", "Montelukast, compared with fluticasone, for control of asthma among 6- to 14-year-old patients with mild asthma: the MOSAIC study.", "Fluticasone propionate compared with zafirlukast in controlling persistent asthma: a randomized double-blind, placebo-controlled trial.", "Effect of budesonide and montelukast in asthmatic children exposed to relevant allergens.", "Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group.", "Roles of angiopoietin-1 and angiopoietin-2 on airway microvascular permeability in asthmatic patients.", "Fluticasone or montelukast for preschool children with asthma-like symptoms: Randomized controlled trial.", "Distribution of therapeutic response in asthma control between oral montelukast and inhaled beclomethasone.", "A comparison of short-term treatment with inhaled fluticasone propionate and zafirlukast for patients with persistent asthma.", "Montelukast versus fluticasone: effects on lung function, airway responsiveness and inflammation in moderate asthma.", "Traditional and patient-centred outcomes with three classes of asthma medication.", "Low-dose fluticasone propionate compared with montelukast for first-line treatment of persistent asthma: a randomized clinical trial.", "Steroid naive eosinophilic asthma: anti-inflammatory effects of fluticasone and montelukast.", "Effects of montelukast and beclomethasone on airway function and asthma control.", "Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group.", "Comparative efficacy of once-daily therapy with inhaled corticosteroid, leukotriene antagonist or sustained-release theophylline in patients with mild persistent asthma.", "Comparative study of budesonide inhalation suspension and montelukast in young children with mild persistent asthma.", "Characterization of within-subject responses to fluticasone and montelukast in childhood asthma.", "Predicting short term response to anti-inflammatory therapy in young children with asthma.", "Role of regular treatment with inhaled corticosteroid or leukotriene receptor antagonist in mild intermittent asthma.", "Oral montelukast versus inhaled beclomethasone in 6- to 11-year-old children with asthma: results of an open-label extension study evaluating long-term safety, satisfaction, and adherence with therapy.", "Fluticasone propionate versus zafirlukast: effect in patients previously receiving inhaled corticosteroid therapy.", "Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma.", "A randomized study comparing the effect of loratadine added to montelukast with montelukast, loratadine, and beclomethasone monotherapies in patients with chronic asthma." ]

[ "Insufficient data exist to evaluate the comparative effects of inhaled corticosteroids (ICS) versus leukotriene receptor antagonist (LTRA) on airway inflammation and quality of life (QoL). The aim of the study was to compare the effectiveness of montelukast compared to budesonide at different doses on QoL and bronchial reactivity in mild-asthmatic adult patients. 45 subjects with bronchial asthma were randomly assigned to a different treatment and divided in 3 treatment groups: A: 400 mg of budesonide twice a day; B: 10 mg of montelukast daily; C: 10 mg of montelukast daily plus 400 mg of budesonide twice a day. At the beginning of the study and at the end of the treatment period (16 weeks) all patients underwent complete clinical evaluation, pulmonary function testing and methacholine challenge test (MCHt). In group A the increase from baseline was 153.4&amp;#x0025;, in group C was 133.2&amp;#x0025;, and in group B 247.7&amp;#x0025;, the latter increase being statistically significant compared to that in the other 2 groups (p&amp;#x003C; 0.005 Wilcoxon test). In all domains the improvement in quality of life in the group treated with montelukast (group B) was significantly greater than that in the group treated with both medications (group C): in particular, the improvement was consistent in the symptoms (p&amp;#x003C; 0.01) and emotions (p&amp;#x003C; 0.01) domains, and weaker in the physical activity (p&amp;#x003C; 0.05). A similar difference was observed between group B and A, but only in the symptoms (p&amp;#x003C;0.01), emotions (p&amp;#x003C;0.01), and environmental stimuli domains (p&amp;#x003C;0.05). The personal perception of their own disease is important for a correct therapeutic management of asthma. In order to optimize the treatment, a complete adherence of the patient to the treatment itself is required, to be achieved through simplification of therapeutic schedule and easy administration of medications. Montelukast may be considered a valid alternative in the treatment of mild-persistent asthma, both for the clinical and functional benefits and for the great advantage of the once-daily dosage, which consistently improves the compliance with the chronic treatment of the disease.", "Insufficient data exist to evaluate the comparative effects of inhaled corticosteroids versus leukotriene receptor antagonists on airway inflammation and remodelling. The aim of the study was to evaluate the effectiveness and safety of montelukast versus budesonide at different doses on bronchial reactivity in mild-asthmatic adult patients.\n A total of 40 patients were randomly assigned to a different treatment and divided in 2 treatment groups (A, B) as follows: A-10 mg of montelukast daily; B-400 mg of budesonide twice a day.\n We studied 40 subjects (21 males, 19 females) divided in two groups of 20 subjects each: group A with mean age 25.16 +/- 7.68 years, group B with mean age 26.18 +/- 6.15 years. After 16 weeks of treatment in the group A the PC20 (provocative concentration of methacholine which cause a fall of FEV1 > or = 20%) was 620.12 +/- 140.54 micrograms/mL significantly highly compared to basal value of 315.75 +/- 100.16 micrograms/mL (p < 0.02). In the group B the PC20 was 795.67 +/- 312.76 micrograms/mL significantly highly compared to basal value of 342.87 +/- 132.38 micrograms/mL (p < 0.001). We not found differences in FEV1, FVC e PEF before and after the treatment.\n Montelukast may be considered a valid alternative in the treatment of mild-persistent asthma, both for the benefits on bronchial reactivity and for the great advantage of the once-daily dosage, which consistently improves the compliance with the chronic treatment of the disease.", "In this study, 647 subjects stable on fluticasone propionate/salmeterol Diskus 100/50 mcg BID (FSC) were randomized to continue FSC 100/50 mcg BID or \"step down\" to either fluticasone propionate (FP) 100 mcg BID, salmeterol (SAL) 50 mcg BID, or montelukast (MON) 10 mg once daily for 16 weeks. Overall asthma control significantly improved in the FSC group; whereas, \"stepping down\" to FP, SAL, or MON resulted in deterioration in asthma control, as determined by decreased measures of lung function and clinical features. This study provides support that treatment of both inflammation and smooth muscle dysfunction may be necessary to achieve and maintain asthma control in patients uncontrolled on ICS.", "Levels of an immunoregulatory and anti-inflammatory cytokine IL-10 are reduced in asthmatic airways, potentially contributing to more intense inflammation. Triamcinolone has anti-inflammatory properties and the anti-inflammatory effects of montelukast and formoterol have been discussed.\n The purpose of this study was to define the effect of treatment with triamcinolone, montelukast and formoterol on the serum level of IL-10, eosinophil blood counts, eosinophil cationic response (ECP) and clinical parameters (symptom score, FEV1 and PC20H) in children with moderate asthma.\n An 8-week, placebo-controlled and randomized, double-blind trial was carried out. The subjects were 91 children with moderate atopic asthma who were allergic to dust mite. Patients were randomly allocated to receive 400 microg triamcinolone (n = 19), 5 or 10 mg (according to age) montelukast (n = 18), 24 microg formoterol (n = 18) or placebo (n = 36).\n Seventy-nine children completed the study. After treatment with triamcinolone and montelukast the level of IL-10 in blood serum significantly increased, eosinophil blood counts and ECP levels significantly decreased and all clinical parameters improved; treatment with formoterol had no effect on IL-10 level, eosinophil blood counts in serum and bronchial hyper-reactivity; ECP level significantly decreased after treatment and asthma symptoms and FEV1 improved significantly. Mean IL-10 levels in serum before and after treatment with triamcinolone were 7.23 pg/mL with 95% CI, 6.74 -7.72% and 14.24 pg/mL with 95% CI, 11.6-16.88%, respectively (P < 0.001); with montelukast they were 6.59 pg/mL with 95% CI, 6.26-7.23% and 10.94 pg/mL with 95% CI, 8.24-12.65%, respectively (P < 0.002); with formoterol they were 7.06 pg/mL with 95% CI, 6.61-7.52% and 7.04 pg/mL with 95% CI, 6.15-7.93%. We found statistically significant correlations between serum level of IL-10 and serum level of ECP after treatment with triamcinolone and montelukast.\n This study demonstrates that one possible way by which triamcinolone and montelukast contribute to inhibition of inflammation is by increasing IL-10 levels.", "More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children.\n The Pediatric Asthma Controller Trial (PACT) compared the effectiveness of 3 regimens in achieving asthma control.\n A total of 285 children (ages 6-14 years) with mild-moderate persistent asthma on the basis of symptoms, and with FEV(1) >or= 80% predicted and methacholine FEV(1) PC(20) <or= 12.5 mg/mL, were randomized to 1 of 3 double-blind 48-week treatments: fluticasone 100 microg twice daily (fluticasone monotherapy), fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening (PACT combination), and montelukast 5 mg in the evening. Outcomes included asthma control days (primary outcome), exacerbations, humanistic measurements, and pulmonary function measurements.\n Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes, including percent of asthma control days, but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity (P = .015), maximum bronchodilator response (P = .009), exhaled nitric oxide (P < .001), and PC(20) (P < .001). Fluticasone monotherapy was superior to montelukast for asthma control days (64.2% vs 52.5%; P = .004) and for all other control outcomes. Growth over 48 weeks was not statistically different (fluticasone, 5.3 cm; PACT combination, 5.3 cm; montelukast, 5.7 cm).\n Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast. However, fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control. Growth was similar in all groups.\n Therefore, of the regimens tested, the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1) >or= 80% predicted, confirming current guideline recommendations.", "Eosinophil-mediated damage to the respiratory epithelium is a major pathogenetic mechanism in asthma. Glucocorticoids have confirmed antiinflammatory properties and effect of formoterol, montelukast and nedocromil on markers of inflammation has been studied. Eosinophil blood counts and eosinophil cation protein (ECP) serum level are often use as markers of clinical monitoring of the disease activity. To evaluate the effect of treatment on allergic inflammation, we measured eosinophil blood counts and ECP serum level, and clinical parameters before and after 4 weeks treatment with triamcinolon, montelukast, nedocromil, formoterol. It was 8 week, placebo-controlled and randomized, double blind trial of 154 children with moderate atopic asthma. Patients were randomly allocated to receive 400 mg triamcinolon (n = 28), 5 or 10 mg (according to age) montelukast (n = 27), 16 mg nedocromil (n = 26), 24 micrograms formoterol (n = 28) or placebo (n = 45). 140 children completed the study. After treatment with triamcinolon and montelukast eosinophil blood counts significantly decreased, after treatment with triamcinolon, montelukast and nedocromil ECP serum level significantly decreased; all clinical parameters improved after treatment with each drug; treatment with triamcinolon had the strongest effect on most parameters (except of FEV1). Mean eosinophil blood counts before and after treatment with triamcinolon were 277.4 and 187.2 cells/mm3 respectively (p < 0.001); with montelukast were 279.6 and 250.7 cells/mm3 respectively (p = 0.002); with nedocromil were 181.7 and 170.1 cells/mm3 respectively (p < 0.183); with formoterol were 276.4 and 264.1 cells/mm3 respectively (p = 0.2). Mean ECP serum levels before and after treatment with triamcinolon were 94.3 and 63.5 micrograms/l respectively (p < 0.001); with montelukast were 85.1 micrograms/l and 71.2 micrograms/l respectively (p < 0.001); with nedocromil were 92.6 and 80.1 micrograms/l respectively (p < 0.001); with formoterol were 95.9 micrograms/l and 87.8 micrograms/l (p = 0.05). We found significant correlation between ECP and hyperresponsiveness after treatment with triamcinolon, montelukast. This study shows that triamcinolon, montelukast contribute to inhibition of allergic inflammation by decreasing eosinophil blood counts and ECP. The serum level of ECP seems to be a good clinical marker of monitoring the disease.", "Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma. Aim: To determine whether montelukast is as effective as budesonide in controlling mild persistent asthma as determined by FEV(1).\n Between November 2003 to October 2005, participants aged 5-15 years with recently diagnosed mild persistent asthma (n = 62) were randomized to oral montelukast (5 mg daily) [N(1) = 30] or inhaled budesonide (400 microg per day in two doses) [N(2) = 32] in a single center, double-blind study.\n Baseline demographic and spirometric parameters were comparable. The median (95% confidence interval) percentage predicted FEV(1) was similar in the two groups after 12 weeks of treatment (budesonide: 76.70 (67.96-90.53%), montelukast: 75 (67.40-88.47)%; p = 0.44). There was similar improvement in spirometric parameters and clinical symptom scores in both the groups. There was no statistically significant difference between the groups in the need for rescue drugs as well as side effects reported by parents.\n Montelukast is as effective as inhaled budesonide in the treatment of mild persistent asthma in children aged 5-15 years. Montelukast may be used as an alternative to low dose inhaled corticosteroids for management of mild persistent asthma.", "To determine the anti-inflammatory actions of pranlukast, a cysteinyl leuklotriene receptor antagonist, we measured exhaled nitric oxide (NO) concentrations and eosinophil ratio in induced sputum of three groups of mild asthmatics (n = 30): treated with bronchodilators alone, with bronchodilators and inhaled steroid (beclomethasone dipropionate; 400 microg/day), and bronchodilators and pranlukast (450 mg/day). Pranlukast (450 mg/day) reduced the eosinophil ratio in the induced sputum significantly (p < 0.01) without a major effect on the concentration of exhaled NO. Pranlukast also increased values of peak expiratory flow significantly (p < 0.05). Pranlukast may be useful for mild asthmatics, in part through its ability to suppress eosinophilic airway infiltration.", "Few studies have compared the efficacy of inhaled corticosteroids and leukotriene modifiers for the treatment of persistent asthma.\n Our purpose was to compare the efficacy of a low dose of inhaled fluticasone propionate (FP) with that of oral zafirlukast in the treatment of persistent asthma previously treated with short-acting beta(2)-agonists alone.\n A 12-week, randomized, double-blind, double-dummy, multicenter study was conducted in 451 patients aged 12 years and older with asthma who were symptomatic on short-acting beta(2)-agonists alone. After an 8- to 14-day run-in period, patients were randomized to treatment with FP 88 microg twice daily or zafirlukast 20 mg twice daily.\n Treatment with FP was more effective than treatment with zafirlukast in increasing morning FEV(1) (by 0.42 L vs 0.20 L over baseline, P <.001), morning peak expiratory flow (by 49.94 L/min vs 11.68 L/min over baseline, P <. 001), and evening PEF (by 38.91 L/min vs 10.50 L/min over baseline, P <.001). Statistically significant differences between the two treatments in FEV(1) were noted after the first observation (week 4) and in morning and evening peak expiratory flow by week 2. Mean change in percentage of symptom-free days was greater with FP than with zafirlukast (28.5% of days vs 15.6% of days, P <.001) and FP significantly increased the percentage of rescue-free days by 40.4% of days compared with 24.2% of days with zafirlukast (P <.001). Treatment with FP significantly reduced albuterol use by 2.39 puffs per day compared with 1.45 puffs per day (P <.001) and increased the percentage of nights with no awakenings by 21.2% of nights compared with 8.0% of nights with zafirlukast (P <.001).\n The clinical effectiveness of a low dose of FP as first-line therapy in patients with persistent asthma who are symptomatic on beta(2)-agonists alone is superior to that of zafirlukast.", "Apoptosis may be important in limiting airway eosinophilia. Treatment with leukotriene antagonists decreases the number of eosinophils in both peripheral blood and sputum.\n To assess the effect of montelukast on eosinophil apoptosis in a group of patients with mild persistent asthma (MPA) and to compare this effect with the apoptotic effect of fluticasone propionate (FP).\n Randomly selected patients with MPA (n = 22) who had not taken anti-inflammatory therapy within the preceding 12 months were included in the study. The sputum induction procedure was performed and the patients were divided into two groups: group 1 (n = 10) received FP 250 microg/day and group 2 (n = 22) received montelukast 10 mg/day orally for 4 weeks. Sputum induction was repeated after the treatment period. The resulting cytospin slides were stained by Wright's stain and morphologic changes in apoptotic eosinophils were assessed by the use of light microscopy by two blinded expert pathologists. Serum soluble Fas ligand (sFasL) concentrations were measured by an ELISA method at baseline and after treatment in both groups, as well as in a group of healthy subjects.\n In within-group comparisons, the apoptotic ratio (AR) increased at the end of the study period in group 1 (p = 0.05). In the group treated with FP the ratio of sputum eosinophils significantly decreased (p = 0.02), and the AR significantly increased (p < 0.005). No differences were found in the two study groups in serum sFasL levels at the end of the treatment period compared with baseline values (p > 0.05).\n Our findings demonstrate that 4 weeks' treatment with a CysLT receptor antagonist (montelukast) resulted in an increase in eosinophil apoptosis comparable to that produced by FP, suggesting that induction of apoptosis may be a potential mechanism for the mode of action of CysLT receptor antagonists in asthma.", "Current guidelines advocate the use of preventative anti-inflammatory therapy for mild persistent asthma.\n We compared the efficacy and anti-inflammatory profiles of a leukotriene receptor antagonist and a low dose of inhaled corticosteroid in patients with mild persistent asthma.\n Twenty-one adult patients with mild asthma received 4 weeks of either once-daily inhaled hydrofluoroalkane triamcinolone acetonide (450 microg/day ex-actuator dose) or oral montelukast (10 mg/day) in a randomized, placebo-controlled, single-blinded crossover study. Measurements were made before and after 2 and 4 weeks of each treatment.\n At the endpoint (after 4 weeks), triamcinolone and montelukast had improved the primary outcome (provocative dose of methacholine required to produce a 20% fall in FEV(1)) in comparison with placebo (P <.05), there being no difference between the treatments (1.09-fold; 95% CI 0.73 to 1.63). Triamcinolone was better than placebo or montelukast for effects on all other surrogate inflammatory markers (P <.05), including exhaled nitric oxide, blood eosinophils, serum eosinophil cationic protein, plasma intracellular circulating adhesion molecule 1, and plasma E-selectin. Both treatments improved (P <.05) morning and evening peak flow, nighttime beta2-agonist use, and symptoms in comparison with placebo, though triamcinolone was better than montelukast (P <.05) with regard to peak flow. Triamcinolone produced suppression (P <.05) of overnight urinary cortisol/creatinine and serum osteocalcin.\n Once-daily inhaled corticosteroid and leukotriene antagonist improved the primary outcome variable of bronchial hyperresponsiveness to a similar degree.", "Although guidelines recommend daily therapy for patients with mild persistent asthma, prescription patterns suggest that most such patients use these so-called controller therapies intermittently. In patients with mild persistent asthma, we evaluated the efficacy of intermittent short-course corticosteroid treatment guided by a symptom-based action plan alone or in addition to daily treatment with either inhaled budesonide or oral zafirlukast over a one-year period.\n In a double-blind trial, 225 adults underwent randomization. The primary outcome was morning peak expiratory flow (PEF). Other outcomes included the forced expiratory volume in one second (FEV1) before and after bronchodilator treatment, the frequency of exacerbations, the degree of asthma control, the number of symptom-free days, and the quality of life.\n The three treatments produced similar increases in morning PEF (7.1 to 8.3 percent; approximately 32 liters per minute; P=0.90) and similar rates of asthma exacerbations (P=0.24), even though the intermittent-treatment group took budesonide, on average, for only 0.5 week of the year. As compared with intermittent therapy or daily zafirlukast therapy, daily budesonide therapy produced greater improvements in pre-bronchodilator FEV1 (P=0.005), bronchial reactivity (P<0.001), the percentage of eosinophils in sputum (P=0.007), exhaled nitric oxide levels (P=0.006), scores for asthma control (P<0.001), and the number of symptom-free days (P=0.03), but not in post-bronchodilator FEV1 (P=0.29) or in the quality of life (P=0.18). Daily zafirlukast therapy did not differ significantly from intermittent treatment in any outcome measured.\n It may be possible to treat mild persistent asthma with short, intermittent courses of inhaled or oral corticosteroids taken when symptoms worsen. Further studies are required to determine whether this novel approach to treatment should be recommended.\n Copyright 2005 Massachusetts Medical Society.", "One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control.\n To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke.\n In a multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast.\n Primary outcome was change in prebronchodilator FEV(1) in smokers versus nonsmokers. Secondary outcomes included peak flow, PC(20) methacholine, symptoms, quality of life, and markers of airway inflammation. Despite similar FEV(1), bronchodilator response, and sensitivity to methacholine at baseline, subjects with asthma who smoked had significantly more symptoms, worse quality of life, and lower daily peak flow than nonsmokers. Adherence to therapy did not differ significantly between smokers and nonsmokers, or between treatment arms. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers and nonsmokers, but increased FEV(1) (170 ml, p = 0.0003) only in nonsmokers. Montelukast significantly increased a.m. peak flow in smokers (12.6 L/min, p = 0.002), but not in nonsmokers.\n In subjects with mild asthma who smoke, the response to inhaled corticosteroids is attenuated, suggesting that adjustments to standard therapy may be required to attain asthma control. The greater improvement seen in some outcomes in smokers treated with montelukast suggests that leukotrienes may be important in this setting. Larger prospective studies are required to determine whether leukotriene modifiers can be recommended for managing asthma in patients who smoke.", "Inhaled corticosteroids are currently regarded as the gold standard in anti-inflammatory therapy, however, leukotriene receptor antagonists have been ascribed anti-inflammatory properties.\n We directly compared the anti-inflammatory effects of inhaled fluticasone propionate (FP, 100 microg Diskus, twice daily) and oral montelukast (MON 10 mg, nocte) in bronchial biopsies of patients with asthma in a double-blind, double-dummy, parallel-group design.\n Bronchial biopsies, serum and urine samples were collected from 36 atopic asthmatics before and after 8 weeks of treatment. Activated T cells (CD25+), eosinophils (MBP+) and mast cells (tryptase+) were analysed by immunohistochemistry. Serum eosinophil cationic protein (ECP) and IL-5 were analysed by radio and enzyme immunoassay (EIA), respectively. Urinary 9alpha-11beta-PGF2 and leukotriene E4 (LTE4) were measured by EIA.\n A comparison of changes from baseline [FP/MON ratio (95% confidence interval)] of activated T cells was not different when subjects were treated with FP compared to treatment with MON [1.00 (0.18-4.86); P=0.924]. Following treatment, mast cells in the FP group were significantly lower than in the group treated with MON [0.39 (0.16-0.97); P=0.041]. There was no difference in the number of eosinophils in the lamina propria following either treatment [0.54 (0.05-2.57); P=0.263]. However, treatment with FP resulted in a significantly greater decrease in serum ECP, compared to treatment with MON [0.37 (0.25-0.71); P=0.002].\n FP appears to be superior to MON as an anti-inflammatory therapy in mild asthmatics.", "Asthma is one of the most common chronic diseases in children and adults. Recent studies have shown that in asthmatic patients treated with inhaled corticosteroids there is a better disease’s control when adding a second drug, than increasing the corticosteroid’s dose. The aim of this study has been to evaluate the effectiveness and tolerance of zafirlukast, a leukotriene receptor antagonist, versus budesonide in clinically steady patients with mild persistent bronchial asthma. We have enrolled 36 subjects non smokers, with mild persistent bronchial asthma and 12 healthy subjects as control group. At the beginning of this study and at the end of the treatment (8 weeks), all patients underwent complete clinical work-up, pulmonary function testing (FEV1, PEF and FVC) and methacholine challenge test. The patients were divided into 3 groups: group A) 20 mg of zafirlukast twice a day; group B) 400 mg of budesonide twice a day; group C) 20 mg of zafirlukast twice a day and 400 mg of budesonide twice a day. Basal FEV1 and PEF presented no significant statistical differences between control subjects and patients of group A, B and C. After eight weeks there were no significant changes for FEV1 and PEF among the three groups. After therapy a strong significant increase of PD20 was documented in group A (p&#x003C;0.005), group B (p&#x003C;0.001) and group C (p&#x003C;0.005), respect to baseline values. The antileukotriene drugs could be taken as an alternative drug, or in association with low-dose inhaled corticosteroids, in patients with mild persistent asthma, both for their clinical effectiveness and their easy ingestion, which is confirmed in compliance studies on inhaled steroids.", "We studied 51 atopic non-smoking subjects who were divided to four treatments groups: (A) montelukast 10mg daily, (B) budesonide 400 microg twice a day (bid), (C) montelukast 10 mg daily plus budesonide 400 microg bid and (D) budesonide 800 microg bid. Bronchial responsiveness was assessed before and after 12 weeks of treatment. The bronchial responsiveness, evaluated by means of PC(20) values, showed a strong significant increase in groups B, C and D, and a weak but significant rise in group A, when compared to basal data. Regarding other pulmonary parameters (FEV(1), PEF) there were no significant differences among the groups after 12 weeks of therapy. A statistical significance was founded after therapy between group A and C (p < 0.05), but not between the group B and D treated with only budesonide at different doses. No significant differences was observed in the side effect pattern among the various treatments. The study data demonstrated that administration of montelukast provided an important and additional effect on bronchial hyperresponsiveness. Oral administration represents a significant advantage over the majority of other anti-asthmatic drugs. Our results confirm the anti-inflammatory properties of both the inhaled corticosteroid (ICS) and montelukast and the possible role of these drugs can have on airway remodelling. While currently low dose ICS remains the reference drug as a controller in mild-moderate persistent asthma, montelukast may be viewed as a possible option, either in monotherapy or in association.\n Copyright 2003 Elsevier Science Ltd.", "Outcome data are needed to base recommendations for controller asthma medication use in school-aged children.\n We sought to determine intraindividual and interindividual response profiles and predictors of response to an inhaled corticosteroid (ICS) and a leukotriene receptor antagonist (LTRA).\n An ICS, fluticasone propionate (100 mug twice daily), and an LTRA, montelukast (5-10 mg nightly, age dependent), were administered to children ages 6 to 17 years with mild-to-moderate persistent asthma using only as-needed bronchodilators in a multicenter, double-masked, 2-sequence, 16-week crossover trial. Clinical, pulmonary, and inflammatory responses to these controllers were evaluated.\n Improvements in most clinical asthma control measures occurred with both controllers. However, clinical outcomes (asthma control days [ACDs], the validated Asthma Control Questionnaire, and albuterol use), pulmonary responses (FEV(1)/forced vital capacity, peak expiratory flow variability, morning peak expiratory flow, and measures of impedance), and inflammatory biomarkers (exhaled nitric oxide [eNO]) improved significantly more with fluticasone than with montelukast treatment. eNO was both a predictor of ACDs (P = .011) and a response indicator (P = .003) in discriminating the difference in ACD response between fluticasone and montelukast.\n The more favorable clinical, pulmonary, and inflammatory responses to an ICS than to an LTRA provide pediatric-based group evidence to support ICSs as the preferred first-line therapy for mild-to-moderate persistent asthma in children. eNO, as a predictor of response, might help to identify individual children not receiving controller medication who achieve a greater improvement in ACDs with an ICS compared with an LTRA.", "To determine whether montelukast is as effective as fluticasone in controlling mild persistent asthma as determined by rescue-free days.\n Participants aged 15 to 85 years with mild persistent asthma (n = 400) were randomized to oral montelukast (10 mg once nightly) or inhaled fluticasone (88 mug twice daily) in a year-long, parallel-group, multicenter study with a 12-week, double-blind period, followed by a 36-week, open-label period.\n The mean percentage of rescue-free days was similar between treatments after 12 weeks (fluticasone: 74.9%, montelukast: 73.1%; difference = 1.8%, 95% confidence interval [CI]: -3.2% to 6.8%) but not during the open-label period (fluticasone: 77.3%, montelukast: 71.1%; difference = 6.2%, 95% CI: 0.8% to 11.7%). Although both fluticasone and montelukast significantly improved symptoms, quality of life, and symptom-free days during both treatment periods, greater improvements occurred with fluticasone in lung function during both periods and in asthma control during open-label treatment. Post hoc analyses revealed a difference in rescue-free days favoring fluticasone in participants in the quartiles for lowest lung function and greatest albuterol use at baseline.\n In patients with mild persistent asthma, rescue-free days and most asthma control measures improved similarly with fluticasone or montelukast over the short term, but with prolonged open-label treatment, asthma control improved more with fluticasone. Improved asthma control with fluticasone appeared to occur in those with decreased lung function and greater albuterol use at baseline. In the remaining patients, the two treatments appeared to be comparable. These results suggest that classification criteria for mild persistent asthma may need to be re-evaluated.", "Since IgE is considered to play a crucial role in allergic immune responses, the reduction of free IgE level has been an attractive target in the treatment of allergic diseases. The present study was conducted to determine the effects of a 6-month treatment with different doses of inhaled budesonide and montelukast sodium in children with newly diagnosed atopic asthma.\n In this randomized, double-blind, double-dummy trial, 51 children with newly diagnosed asthma and sensitivity to house-dust mites were randomly allocated to receive budesonide (in two different doses 400 or 800 mcg) or montelukast for 6 months. The primary end point was the level of serum total and specific IgE before and after treatment. The secondary end points were clinical parameters and forced expiratory volume in 1s (FEV1).\n After 6 months of treatment, a high dose of inhaled corticosteroid and montelukast, significantly decreased levels of total and specific IgE. Medium dose of inhaled corticosteroid had no effect on total and specific IgE serum level. Clinical score and FEV1 significantly improved after 6 months of treatment with medium (P = 0.002) and high dose (P = 0.001) of inhaled budesonide and montelukast (P = 0.002). There were no differences between groups in changes of all clinical parameters after treatment.\n Only high doses of inhaled corticosteroids and montelukast decreased the serum IgE levels. Perhaps long-term treatment with montelukast will be beneficial to asthma patients by decreasing IgE levels.", "Asthma severity can be judged by measurements of symptoms, lung function, and medication requirements. The objective was to compare the effect of a 4-wk monotherapy with low-dose triamcinolone, montelukast and nedocromil on asthma control, lung function, eosinophil blood count, and bronchial hyper-reactivity in children with mild to moderate asthma allergic to dust mite. Two hundred fifty-six children, aged 6-18 yr, with mild to moderate asthma, participated in an 8-wk study. This was a three-arm, randomized no blinding or placebo pragmatic trial comparing the effect of triamcinolone acetonide (400 microg/day), inhaled nedocromil and montelukast sodium on clinical parameters of asthma [score, forced expiratory volume in 1 s (FEV(1))], PC20H, and eosinophil blood count. Two hundred forty-six children completed the study. After 4 wk of treatment with triamcinolone and montelukast, FEV(1) and PC20H significantly increased, and mean total symptoms score and mean number of eosinophil count in serum significantly decreased. Triamcinolone had a stronger effect on PC20H than montelukast. Nedocromil improved total asthma symptoms score and lung function. There was a reduction in the daytime and night-time symptom scores after treatment with all three drugs. Triamcinolone and montelukast had a stronger effect on asthma symptoms than nedocromil. There were statistically significant differences in reduction of nocturnal asthma symptoms between the triamcinolone and nedocromil groups (p < 0.001) and between montelukast and nedocromil (p = 0.001) groups, but not between the triamcinolone and montelukast groups. There was a reduction in beta-agonists use after treatment with all three drugs, with the strongest effect of triamcinolone. The study showed the strongest effect of low-dose inhaled steroids on clinical symptoms, lung function, bronchial hyper-reactivity and eosinophil blood count when compared to other asthma medications.", "Pulmonary function tests (PFTs) and especially spirometry measures are useful tools in evaluating early response to treatment of asthma in children mainly due to their worldwide availability. The aim of our study was to determine the effects of anti-asthma treatment in children, equally on FEV(1), FEF25-75%, R(int) and SR(aw) values.\n Children 6-18 years of age with moderate atopic asthma were randomized to 4-week, placebo-controlled, double-blind trial. Patients were randomly allocated to receive 200 microg budesonide (B) (n=29), 5 or 10 mg (according to age) montelukast (M) (n=29), 200 microg B + 5 or 10 mg M (n=29), 200 microg B + 9 microg formoterol (F) (n=29) or placebo (n=27). FEV(1,) FEF25-75%, R(int), SR(aw) were measured before and after treatment.\n R(int), SR(aw), FEV(1) improved significantly in all active treatment groups while FEF25-75% improved significantly only in BM group and M group. Combination therapy, showed significantly greater effects on R(int) than monotherapy: BM group compared to B group (P=0.01) and M group (P=0.03) and BF group compared to B group (P=0.01) and M group (P=0.04).\n This study shows that using single parameter for monitoring asthma can be misleading. Using combination of lung function techniques provides better assessment of treatment. Results of our study confirm this hypothesis. The best effect on large and small airways was achieved with combined anti-inflammatory therapy.", "Inhaled corticosteroids, leukotriene receptor antagonists, and theophylline are recommended for the treatment of mild persistent asthma. The aim of this study was to compare the changes in sputum total cell and eosinophil counts, and eosinophil cationic protein (ECP) levels in serum and sputum following treatment with leukotriene receptor antagonists, inhaled corticosteroids, and theophylline in patients with mild persistent asthma.\n Total cell counts, eosinophil percentage, and ECP levels in induced sputum and serum were determined both before and after treatment. Prior to sputum induction, FEV1 and PEF values and symptom scores were recorded at baseline and after 8 weeks of treatment. After baseline measurements, the asthmatic patients (n = 30) were randomized into three groups. A total of 10 patients were treated with zafirlukast, 20 mg bd, 10 with budesonide inhaler 200 microg bd, and 10 with theophylline 200 mg bd.\n There were significant decreases in sputum total cell counts and eosinophil percentage in all treatment groups. However, the decrease in sputum eosinophil counts was more significant in the corticosteroid-treated group. Although sputum ECP levels decreased significantly in the groups treated with zafirlukast and budesonide (zafirlukast group, 580-135 microg/L, P < 0.01; budesonide group, 683-268 microg/L, P < 0.01), the decrease was not statistically significant in the theophylline-treated group (498-361 microg/L, P > 0.05). In contrast, there were no significant changes in serum ECP levels in any of the treatment groups.\n All three treatments resulted in significant decreases in sputum total cell counts and eosinophil percentage, but the decrease in sputum ECP level was only seen in the groups treated with budesonide and zafirlukast. These results suggest that although all three treatments are considered as first-line treatments in most consensuses, theophylline seems to have less of an inhibitory effect on eosinophil activation.", "To evaluate efficacy, safety, health outcomes, and cost-effectiveness of fluticasone propionate (FP) versus montelukast (MON) in 342 children (6 to 12 years of age) with persistent asthma.\n Randomized, double-blind, 12-week study of treatment with FP inhalation powder 50 mug twice daily or MON chewable 5 mg once daily for 12 weeks.\n Compared with MON, FP significantly increased mean percent change from baseline FEV1 (forced expiratory volume in 1 second) (P=.002), morning PEF (peak expiratory flow) (P=.004), evening PEF (P=.020), and percent rescue-free days (P=.002) at end point, and it significantly reduced nighttime symptom scores (P <.001) and mean total (P=.018), and nighttime (P <.001) albuterol use. Withdrawals from the study were more frequent with MON (21%) than with FP (13%). Adverse events (69% vs 71%) and mean end point to baseline 12-hour urinary cortisol excretion ratios were similar. Parents and physicians were more satisfied with FP treatment than with MON (P=.006 and P=.016, respectively, at Week 12). Mean total daily asthma-related cost per patient in the FP group was approximately one-third of that in the MON group ($1.25 vs $3.49).\n FP was significantly more effective than MON in improving pulmonary function, asthma symptoms, and rescue albuterol use. Both therapies had similar safety profiles. Parent- and physician-reported satisfaction ratings were higher with FP treatment, and asthma-related costs were lower.", "Treatment guidelines recommend the use of inhaled corticosteroids in patients with asthma who have persistent symptoms and the \"stepping down\" of therapy to the minimum needed to maintain control of asthma. Whether patients with asthma that is well controlled with the use of inhaled corticosteroids twice daily can receive a step-down treatment with once-daily montelukast (our primary hypothesis) or once-daily fluticasone propionate plus salmeterol (our secondary hypothesis) has not yet been determined.\n We randomly assigned 500 patients with asthma that was well controlled by inhaled fluticasone (100 microg twice daily) to receive continued fluticasone (100 microg twice daily) (169 patients), montelukast (5 or 10 mg each night) (166 patients), or fluticasone (100 microg) plus salmeterol (50 microg) each night (165 patients). Treatment was administered for 16 weeks in a double-blind manner. The primary outcome was the time to treatment failure.\n Approximately 20% of patients assigned to receive continued fluticasone or switched to treatment with fluticasone plus salmeterol had treatment failure, as compared with 30.3% of subjects switched to montelukast. The hazard ratio for both comparisons was 1.6 (95% confidence interval, 1.1 to 2.6; P=0.03). The percentage of days on which patients were free of asthma symptoms (78.7 to 85.8%) was similar across the three groups.\n Patients with asthma that is well controlled with the use of twice-daily inhaled fluticasone can be switched to once-daily fluticasone plus salmeterol without increased rates of treatment failure. A switch to montelukast results in an increased rate of treatment failure and decreased asthma control; however, patients taking montelukast remained free of symptoms on 78.7% of treatment days. (ClinicalTrials.gov number, NCT00156819 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.", "To compare the efficacy and safety of fluticasone propionate and zafirlukast in patients with relatively stable persistent asthma who were previously treated with inhaled corticosteroids and short-acting beta(2)-agonists.A total of 440 patients (> or =12 years of age) previously treated with inhaled corticosteroids (beclomethasone dipropionate or triamcinolone acetonide) and short-acting beta(2)-agonists were included in this randomized double-blind study. After an 8-day run-in period, patients were treated with fluticasone (88 microg) or zafirlukast (20 mg) twice daily for 6 weeks. Outcome measures included pulmonary function (forced expiratory volume in 1 second [FEV(1)], peak expiratory flow [peak flow]), albuterol use, asthma symptoms, withdrawals due to lack of efficacy, and asthma exacerbations. Patients treated with fluticasone (n = 224) experienced greater mean increases in FEV(1) (0.24 L vs. 0.08 L, P <0.001), morning peak flow (30 L/min vs. 6 L/min, P <0.001), and evening peak flow (23 L/min vs. 5 L/min, P <0.001) during the study than did those treated with zafirlukast (n = 216). Fluticasone-treated patients had significantly greater increases in the mean percentages of symptom-free days (22% vs. 8%, P <0.001), rescue-free days (23% vs. 10%, P = 0.002), nights with uninterrupted sleep (<1% vs. -5%, P = 0.006), and fewer asthma exacerbations (1% vs. 6%, P = 0.005). Fewer fluticasone-treated patients were withdrawn due to lack of efficacy (2% vs. 13%, P <0.001).Inhaled fluticasone was more effective than zafirlukast in maintaining or improving asthma control in patients with relatively stable asthma who were switched from low-dose inhaled corticosteroids.", "Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma.\n The Montelukast Study of Asthma in Children (MOSAIC study) was a 12-month, multicenter, randomized, double-blind, noninferiority trial to determine the effect of once-daily, orally administered montelukast (5 mg) (n = 495), compared with twice-daily, inhaled fluticasone (100 microg) (n = 499), on the percentage of asthma rescue-free days (RFDs) (any day without asthma rescue medication and with no asthma-related resource use). Patients 6 to 14 years of age had mild persistent asthma (average percentage of predicted forced expiratory volume in 1 second: 87.2%; RFDs at baseline: 64%). Montelukast would be considered not inferior to fluticasone if the upper limit of the 95% confidence interval for the difference in mean percentages of RFDs (fluticasone minus montelukast) was above -7% (a difference of approximately 2 days/month).\n The mean percentage of RFDs was 84.0% in the montelukast group and 86.7% in the fluticasone group. The least-squares mean difference was -2.8% (95% confidence interval: -4.7% to -0.9%), within the noninferiority limit of -7%. The proportion of patients requiring systemic corticosteroids and the number of patients with an asthma attack were greater in the montelukast group. Both montelukast and fluticasone were well tolerated.\n Montelukast was demonstrated to be not inferior to fluticasone in increasing the percentage of RFDs among 6- to 14-year-old patients with mild asthma. Secondary end points, including percentage of predicted forced expiratory volume in 1 second value, days with beta-receptor agonist use, and quality of life, improved in both groups but were significantly better in the fluticasone treatment group.", "The objective of our study was to compare the efficacy and safety of fluticasone propionate (an inhaled corticosteroid) with zafirlukast (a leukotriene modifier) for persistent asthma.\n In this randomized placebo-controlled, parallel-group, double-blind, double-dummy trial, patients underwent an 8- to 14-day run-in period followed by 12 weeks of treatment with inhaled fluticasone propionate (88 mg twice daily by metered-dose inhaler), oral zafirlukast (20 mg twice daily), or placebo.\n We included a total of 338 persistent asthma patients, 12 years of age or older, using short-acting b2-agonists alone.\n measured Efficacy outcomes included changes in pulmonary function, asthma symptoms, rescue albuterol use, nighttime awakenings due to asthma, and quality of life. Safety outcomes included asthma exacerbations, adverse events, and clinically significant laboratory test results.\n After 12 weeks of treatment, patients taking fluticasone propionate experienced significantly greater improvements in all clinical parameters (symptom scores, percentages of symptom-free and albuterol-free days, albuterol use, and nighttime awakenings) compared with patients taking zafirlukast (P <.05) or placebo (P <.05). Treatment with fluticasone propionate resulted in significantly greater improvements in pulmonary function compared with zafirlukast (P <.05) or placebo (P <.05). Fewer fluticasone propionate patients (4%) had an exacerbation requiring oral corticosteroids compared with those taking zafirlukast (12%) or placebo (10%).\n Inhaled fluticasone propionate is more effective than zafirlukast in controlling asthma symptoms, improving pulmonary function, and improving quality of life for patients who are symptomatic with the use of short-acting b2-agonists alone.", "Montelukast has been shown to be effective in controlling the increase in exhaled NO in asthmatic children re-exposed to house dust mite (HDM). This study compared the effect of low dose inhaled budesonide and oral montelukast in preventing the expected relapse of airway inflammation and reactivity in a group of 24 mild asthmatic children allergic to HDM after a brief period of exposure to relevant allergens.\n Lung function, bronchial hyperresponsiveness (BHR) to methacholine (PC(20)), fractional exhaled nitric oxide (FeNO) levels and sputum eosinophilia were evaluated.\n Pulmonary function remained stable. The BHR was unchanged after exposure in the group treated with budesonide, whereas a significant increase (P = 0.028) was observed in the patients receiving montelukast. No significant difference was observed in FeNO levels after exposure to mite antigen in the two groups. In both the groups of asthmatic children we observed a significant increase in sputum eosinophil % after the exposure to mite antigen.\n The significant increase in BHR level observed in the group of children receiving montelukast suggests a more comprehensive effect as disease controller by inhaled steroids than by leukotriene antagonist in allergic asthmatic children re-exposed to relevant allergens.", "The primary objective of this study was to determine whether montelukast, an oral leukotriene receptor antagonist, provides additional clinical benefit to the effect of inhaled corticosteroids. A total of 642 patients with chronic asthma (FEV(1) 50 to 85% of predicted value and at least a predefined level of asthma symptoms) incompletely controlled with inhaled beclomethasone, 200 microg twice daily using a spacer device, during the 4-wk run-in period were randomly allocated, in a double-blind, double-dummy manner to one of four treatment groups: (1) montelukast 10 mg plus continuing inhaled beclomethasone; (2) placebo tablet plus continuing inhaled beclomethasone; (3) montelukast 10 mg and inhaled placebo (after blind beclomethasone removal); and (4) placebo tablet and inhaled placebo (after blind beclomethasone removal). The primary endpoints were FEV(1) and daytime asthma symptoms score. Montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV(1), daytime asthma symptom scores, and nocturnal awakenings. Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control, demonstrating that patients received clinical benefit from inhaled corticosteroids. Blind removal of beclomethasone in the presence of montelukast resulted in less asthma control but not to the level of the placebo group. All treatments were well tolerated; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study. In conclusion, montelukast provided additional asthma control to patients benefitting from, but incompletely controlled on, inhaled beclomethasone.", "Vascular endothelial growth factor (VEGF) increases microvascular permeability. Recently, considerable attention has been devoted to the physiologic roles of angiopoietin-1 and angiopoietin-2 as regulatory factors of VEGF. This study was designed to examine the roles of angiopoietin-1 and angiopoietin-2 in controlling airway microvascular permeability in asthma.\n Levels of these angiogenic factors and airway vascular permeability index were examined in 30 asthmatics and 12 control subjects. After 2-week run-in period, all asthmatics were randomly assigned to receive fluticasone propionate (400 mug/d) or montelukast (10 mg) for 12 weeks.\n VEGF, angiopoietin-1, and angiopoietin-2 levels in induced sputum were significantly higher in asthmatics than in control subjects. We found an inverse correlation between angiopoietin-1 level and vascular permeability index in asthmatics, while there was a positive correlation between angiopoietin-2 level and that index. VEGF and angiopoietin-1 levels were significantly decreased after fluticasone therapy, while VEGF and angiopoietin-2 levels were significantly decreased after montelukast therapy. Although VEGF levels after treatment were different between two groups, vascular permeability index in the montelukast group was the same level as that in the fluticasone group. Moreover, improvement in vascular permeability index after fluticasone therapy was inversely correlated with decrease in angiopoietin-1 level, while that after montelukast therapy was positively correlated with decrease in angiopoietin-2 level.\n Angiopoietin-1 and angiopoietin-2 play complementary and coordinated roles in regulating microvascular permeability stimulated by VEGF in asthma. Combination of corticosteroids with leukotriene antagonists might effectively improve plasma leakage and provide a new strategy in treating bronchial asthma.", "Beneficial effects of anti-inflammatory therapy such as fluticasone propionate (FP) and montelukast (Mk) have been demonstrated in preschool children with asthma. However, comparative studies are lacking in this age group. Therefore, we conducted a study to evaluate and compare the effect of FP and Mk in preschool children with asthma-like symptoms.\n In this multicenter, randomized, placebo-controlled, double-blind, double-dummy trial, children aged 2-6 years with asthma-like symptoms were included. In total, 63 children were randomly allocated to receive FP (25), Mk (18) or placebo (20) for 3 months. The primary outcome was the daily symptom score (wheeze, cough, shortness of breath) as recorded by caregivers in a symptom diary card. Secondary endpoints were rescue medication free days, blood eosinophils and lung function (interrupter technique and forced oscillation technique (FOT)).\n During the 3 months study period, symptoms improved in all 3 groups, with a statistically significant difference between FP and placebo in favor of the FP group (p=0.021). A significant reduction in circulating eosinophils after 3 months of treatment was found in the Mk group only (p=0.008), which was significantly different from the change found in the placebo group (p=0.045). With the exception of frequency dependence (measured by FOT), which showed a difference between FP and Mk after 3 months of treatment in favor of the FP group (p=0.048), no differences in lung function within or between groups were found.\n In spite of a lack of power, our results suggest that FP has a beneficial effect on symptoms and Mk on blood eosinophil level as compared to placebo. Except for a difference in one lung function parameter after 3 months between FP and Mk in favor of the FP group, this study revealed no differences between FP and Mk.", "The distribution of responses in study populations provides a novel method of comparing the benefit of two treatments. This 6-week, randomised, placebo-controlled, double-blind study compared the effectiveness of oral montelukast with inhaled beclomethasone in chronic asthma by assessing the distribution and overlap of patient responses to therapy, as measured by a clinical outcome (asthma control days). A total of 730 adult patients with asthma, age 15-65 yrs, with a forced expiratory volume in one second (FEV1) at baseline of 50-85% of predicted and > or = 15% improvement in FEV1 after inhaled beta-agonist were enrolled. After a 2-week placebo run-in period, patients were randomly allocated to receive montelukast (10 mg once daily), inhaled beclomethasone (200 microg twice daily) or placebo. The primary end-point (per cent of asthma control days) was compared between treatments as the overlap in the response distributions. The overlap of the distribution of responses between the montelukast and beclomethasone groups was 89% for per cent asthma control days and 96% for change from baseline in FEV1. The mean (+/-SD) per cent asthma control days in the montelukast and beclomethasone groups was significantly higher than that in the placebo group (placebo 40.0+/-35.8, montelukast 50.7+/-37.1, beclomethasone 57.9+/-36.1). The mean differences between montelukast and placebo, beclomethasone and placebo, and montelukast and beclomethasone were significant. The mean per cent change (+/-SD) from baseline in FEV1 was 12.1+/-18.7 and 13.9+/-20.8 in the montelukast and beclomethasone groups, respectively, and significantly greater than that in the placebo group (6.4+/-20.1); there was no significant difference between the montelukast and beclomethasone groups in mean values or response distribution. There was also no difference among treatment groups in the frequency of adverse experiences. A comparison of the response distribution is an important approach to comparing therapies; montelukast and beclomethasone provided similar response distributions for the end-point of per cent asthma control days over a 6-week treatment period.", "To compare the short-term efficacy and safety of low-dose fluticasone propionate with that of oral zafirlukast therapy for patients previously treated with beta-2-agonists alone, and to evaluate the potential therapeutic benefit of switching from zafirlukast to a low-dose inhaled corticosteroid.\n This study consisted of a 4-week randomized, double-blind treatment period followed by a 4-week open-label period. Two hundred ninety-four patients > or =12 years old with asthma previously uncontrolled with beta-2-agonists alone were randomly assigned to treatment with low-dose inhaled fluticasone (88 microg twice daily) or oral zafirlukast (20 mg twice daily). After 4 weeks, all patients discontinued their double-blind therapy and received open-label fluticasone (88 microg twice daily). Outcomes included pulmonary function, asthma symptoms, albuterol use, asthma exacerbations, and adverse events.\n During the double-blind treatment period, fluticasone patients had significantly greater improvements in morning peak flow (29.3 L/min vs. 18.3 L/min), percentage of symptom-free days (19.8% vs. 11.6%), and daily albuterol use (-1.8 puffs per day vs. -1.1 puffs per day) compared with zafirlukast patients (P < or =0.025, each comparison). During the open-label treatment period, patients switched from zafirlukast to fluticasone experienced additional improvements in morning peak flow (17.2 L/min), evening peak flow (13.6 L/min), and FEV(1) (0.11 liter) and daily albuterol use (-0.9 puffs daily) compared with values obtained at the end of the double-blind treatment period (P < or =0.001, each comparison).\n Low-dose fluticasone was more effective than zafirlukast in improving pulmonary function and symptoms in patients with persistent asthma. In addition, switching patients from zafirlukast to fluticasone further improved clinical outcomes.", "Whether leukotriene receptor antagonists exhibit adequate anti-inflammatory effects in the treatment of asthma is still a controversial issue. The aim of the present study was to perform a direct comparison of the effects of a 4-week treatment with either montelukast (10 mg, once a day) or low-dose inhaled fluticasone (100 microg b.i.d.) on functional and inflammatory parameters in steroid-naïve patients with moderate asthma. Forty patients (forced expiratory volume in one second (FEV1), 60-80% predicted) were studied in a double-blind, randomised, crossover design. Treatment periods were separated by 3-8 weeks of washout. At the beginning and end of each period, FEV1, airway responsiveness to inhaled methacholine (provocative concentration causing a 20% fall in FEV1 (PC20)), the level of exhaled nitric oxide (NO) and sputum differential cell counts were determined. Only short-acting beta2-agonists were allowed for relief of symptoms. FEV1 increased by 0.50+/-0.07 L (mean+/-SEM) after fluticasone and by 0.37+/-0.07 L after montelukast (p<0.001, each), and PC20 by 1.33+/-0.13 (p<0.001) and 0.15+/-0.17 (NS) doubling doses, respectively. Correspondingly, percentages of sputum eosinophils were reduced by factor 2.7 (p<0.01) and 1.4 (nonsignificant (NS)), and the levels of exhaled NO (at 50 mL x s(-1)) by factor 2.1 (p<0.01) and 1.1 (NS). These data indicate a comparable bronchodilator action of montelukast and fluticasone in patients with moderate asthma, but additional attenuation of airway inflammation by fluticasone as detectable through noninvasive methods.", "Lung function is commonly used as the primary endpoint in asthma clinical trials, but it may not reflect changes which are important to patients. The present study compared changes in, and relationships between, traditional and patient-centred end-points during treatment with three classes of asthma medication. Subjects with mild-to-moderate asthma were randomised to double-blind, double-dummy crossover treatment with eformoterol 12 microg b.i.d. or montelukast 10 mg q.d., then single-blind treatment with fluticasone 250 microg b.i.d./placebo capsules, with 6-week treatment periods and 1-week washouts. Individual \"traditional\" end-points (symptoms, reliever use, forced expiratory volume in one second per cent predicted, morning peak expiratory flow, airway hyperresponsiveness) and \"patient-centred\" end-points (asthma control questionnaire, quality of life, patient global assessments) were assessed. Principal component analysis and linear modelling were used to explore overall rank orders for treatment, and relationships between outcomes. A total of 58 subjects were randomised. The rank order of benefit from eformoterol and fluticasone differed for three factors derived from principal component analysis (eformoterol>fluticasone for symptom/reliever use factor, fluticasone>eformoterol for lung function factor, eformoterol=fluticasone for patient-centred factor). Montelukast was ranked third for all three factors. A significant relationship between patient-based variables and lung function was found only for montelukast treatment. In asthma treatment, traditional end-points do not fully capture patient-centred benefits, and the relationship between end-points differs with medication class.", "Both inhaled corticosteroids and leukotriene modifiers are used in the maintenance treatment of persistent asthma.\n The goal was to compare the efficacy and safety of low-dose fluticasone propionate (FP) and montelukast as first-line maintenance therapy in symptomatic patients by using short-acting beta2-agonists alone to treat persistent asthma.\n In this multicenter, randomized, double-blind, double-dummy, parallel-group study, 533 patients (>15 years old) with persistent asthma who remained symptomatic while taking short-acting beta2-agonists alone were treated with FP (88 microg [2 puffs of 44 microg] twice daily) or montelukast (10 mg once daily) for 24 weeks.\n Compared with treatment with montelukast, treatment with FP resulted in significantly greater improvements at endpoint in morning predose FEV(1) (22.9% vs 14.5%, P <.001), forced midexpiratory flow (0.66 vs 0.41 L/sec, P <.001), forced vital capacity (0.42 vs 0.29 L, P =.002), morning peak expiratory flow (PEF) (68.5 vs 34.1 L/min, P <.001), and evening PEF (53.9 vs 28.7 L/min, P <.001). Similar improvements in PEF were observed in patients with milder asthma (>70%-80% predicted FEV(1)). At endpoint, FP was more effective than montelukast at decreasing rescue albuterol use (3.1 puffs/day vs 2.3 puffs/day, P <.001), asthma symptom scores (-0.85 [48.6% decrease] vs -0.60 [30.5%], P <.001), and nighttime awakenings due to asthma (-0.64 awakenings/night [62% decrease] vs -0.48 awakenings/night [47.5%], P =.023), and FP increased the percentage of symptom-free days (32.0% vs 18.4% of days, P <.001) compared with montelukast. The adverse event and asthma exacerbation profiles for FP and montelukast were similar.\n Low-dose FP is more effective than montelukast as first-line maintenance therapy for patients with persistent asthma who are undertreated and remain symptomatic while taking short-acting beta2-agonists alone.", "Inhaled corticosteroids and leukotriene receptor antagonists reduce airway eosinophilia and have been used as first line anti-inflammatory therapy for mild persistent asthma.\n A multicentre, randomised, placebo controlled, parallel group study was performed to compare the anti-inflammatory effects of fluticasone propionate and montelukast as measured by sputum eosinophils in 50 adults with symptomatic steroid naive asthma and sputum eosinophilia of > or =3.5%.\n Eighteen patients received low dose fluticasone (250 mug/day), 19 received montelukast (10 mg/day), and 13 were given placebo for 8 weeks. Fluticasone treatment resulted in a greater reduction in sputum eosinophils (geometric mean (SD) 11.9 (2.3)% to 1.7 (5.1)%) than montelukast (10.7 (2.3)% to 6.9 (3.8)%; p = 0.04) or placebo (15.4 (2.4)% to 7.8 (4.2)%; p = 0.002), and improvement in FEV(1) (mean (SD) 2.6 (0.9) l to 3.0 (0.9) l) than montelukast (2.8 (0.7) l to 2.8 (0.9) l; p = 0.02) or placebo (2.4 (0.8) l to 2.4 (0.9) l; p = 0.01). Treatment with fluticasone suppressed sputum eosinophilia within a week while montelukast only attenuated it. The effect of montelukast was maximal at 1 week and was maintained over 4 weeks. The effect of fluticasone was maintained over 8 weeks while that of montelukast was not.\n Montelukast is not as effective as low dose fluticasone in reducing or maintaining an anti-inflammatory effect in steroid naive eosinophilic asthma.", "Maintaining asthma control is a major objective of therapy. Traditionally, the effectiveness of asthma therapy has been judged primarily by its effect on airway function rather than on multiaspect asthma control.\n An inhaled corticosteroid and a leukotriene receptor antagonist were compared to determine whether they provided equivalent effects, as judged by days of asthma control.\n In a randomized, multicenter, double-blind, placebo-controlled, parallel-group study, asthmatic patients (n = 782) with FEV(1) percent predicted values of between 50% and 85% and a weekly average beta-agonist use of more than 2 puffs per day were randomized to receive montelukast (10 mg daily), beclomethasone (200 microg twice daily), or placebo treatment for 6 weeks in a double-dummy fashion. We examined the distribution of the primary end point: percentage of days of asthma control. Secondary end points included FEV(1), albuterol use, occurrence of an asthma attack, asthma flare-up, rescue corticosteroid use, sustained asthma control, and adverse experiences.\n The percentage of days of asthma control was almost identical between the montelukast and beclomethasone groups (98% overlap in the distribution). Montelukast was at least equal to beclomethasone, and both were greater than placebo on the basis of frequency of asthma attacks, asthma flare-ups, and rescue corticosteroid use. Beclomethasone had a greater effect than montelukast and both treatments were better than placebo at improving FEV(1).\n Montelukast was as effective as beclomethasone, as judged by indices of clinical control other than FEV(1). When evaluating the outcome of montelukast therapy, FEV(1) might underestimate clinical effectiveness.", "Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma.\n To compare the clinical benefit of montelukast, a once-daily oral leukotriene receptor antagonist; placebo; and inhaled beclomethasone.\n Randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 12-week study.\n 36 sites worldwide.\n 895 patients 15 to 85 years of age with chronic asthma and an FEV1 50% to 85% of predicted.\n Montelukast, 10 mg once daily at bedtime; inhaled beclomethasone, 200 microg twice daily, administered with a spacer device; or placebo.\n Primary end points were daytime asthma symptom score and FEV1. Secondary end points were peak expiratory flow rates in the morning and evening, as-needed beta-agonist use, nocturnal awakenings, asthma-specific quality of life, and worsening asthma episodes.\n Over the 12-week treatment period, the average percentage change from baseline in FEV1 was 13.1% with beclomethasone, 7.4% with montelukast, and 0.7% with placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). The average change from baseline in daytime symptom score was -0.62 for beclomethasone, -0.41 for montelukast, and -0.17 for placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). Each agent improved peak expiratory flow rates and quality of life, reduced nocturnal awakenings and asthma attacks, increased the number of asthma-control days, and decreased the number of days with asthma exacerbations (P < 0.001 for each active treatment compared with placebo for each end point; P < 0.01 for beclomethasone compared with montelukast for each end point). Although beclomethasone had a greater mean clinical benefit than montelukast, montelukast had a faster onset of action and a greater initial effect. The two agents caused similar decreases in peripheral blood eosinophil counts (P < 0.05 for each agent compared with placebo). Both agents had tolerability profiles similar to that of placebo over the 12-week study.\n Although beclomethasone had a larger mean effect than montelukast, both drugs provided clinical benefit to patients with chronic asthma. This finding is consistent with the use of these agents as controller medications for chronic asthma.", "The purpose of this study was to compare the efficacy and safety of the inhaled budesonide, sustained-release theophylline and montelukast, a leukotriene receptor antagonist, in patients with mild persistent asthma. In this single-center, randomized, parallel-group study that not designed blindly and placebo-controlled manner, 74 patients with mild persistent asthma were treated with either inhaled budesonide 400 microg once daily, oral montelukast 10 mg once daily, or sustained-release theophylline 400 mg once daily for 3 months. In all three treatment groups, improvements were attained in overall asthma control. Asthma symptom scores and supplemental beta2-agonist use were quite the same in all three treatment groups (P>0.05). Although inhaled budesonide group resulted in significantly greater improvements compared with the other two groups in the lung functions (P<0.05), the changes in FEV1 and PEF are within the baseline variability and there was no statistically significant difference among the groups when analyzed by treatment month (P>0.05). Exacerbations of asthma were experienced by 16% of the patients in the montekulast group, by 12.5% of the patients in the theophylline group, and by none of the patients in the budesonide group. The adverse event in each of the three groups was 12%, 16% and 16.7%, respectively. It is concluded that the most important clinical parameters do not point that one of the treatments is more effective than others. Treatment with inhaled corticosteroid is preferred, but sustained-release theophylline and leukotriene antagonists are alternative controller medications in mild persistent asthma.", "Budesonide inhalation suspension and the leukotriene receptor antagonist montelukast have demonstrated efficacy in children with mild persistent asthma, but comparative long-term studies in young children are needed.\n To compare the long-term efficacy and safety of budesonide inhalation suspension and montelukast.\n After a run-in period, children 2 to 8 years old with mild asthma or recurrent wheezing were randomized to once-daily budesonide inhalation suspension 0.5 mg or once-daily oral montelukast 4 or 5 mg for 52 weeks. Subjects were stepped up to twice-daily budesonide inhalation suspension or oral corticosteroids for mild or severe asthma worsening, respectively. The primary outcome was time to first additional medication for asthma worsening at 52 weeks. Secondary variables included times to the first additional asthma medication measured at 12 and 26 weeks; times to the first asthma exacerbation (mild and severe) measured at 12, 26, and 52 weeks; exacerbation rates (mild and severe) over a period of 52 weeks; diary variables (eg, peak expiratory flow [PEF]); patient-reported outcomes; and Global Physician and Caregiver Assessments.\n No significant between-group differences were observed for time to first additional asthma medication at 52 weeks; however, time to first additional asthma medication was longer (unadjusted P = .050) at 12 weeks and exacerbation rates were lower over a period of 52 weeks (unadjusted P = .034) for budesonide versus montelukast. Time to first severe exacerbation (requiring oral corticosteroids) was similar in both groups, but the percentage of subjects requiring oral corticosteroids over a period of 52 weeks was lower with budesonide (25.5% vs 32.0%). Peak flow and Caregiver and Physician Global Assessments favored budesonide.\n Both treatments provided acceptable asthma control; however, overall measures favored budesonide inhalation suspension over montelukast.\n These findings are consistent with studies in older children demonstrating better outcomes with inhaled corticosteroids versus montelukast.", "Responses to inhaled corticosteroids (ICSs) and leukotriene receptor antagonists (LTRAs) vary among asthmatic patients.\n We sought to determine whether responses to ICSs and LTRAs are concordant for individuals or whether asthmatic patients who do not respond to one medication respond to the other.\n Children 6 to 17 years of age with mild-to-moderate persistent asthma were randomized to one of 2 crossover sequences, including 8 weeks of an ICS, fluticasone propionate (100 microg twice daily), and 8 weeks of an LTRA, montelukast (5-10 mg nightly depending on age), in a multicenter, double-masked, 18-week trial. Response was assessed on the basis of improvement in FEV 1 and assessed for relationships to baseline asthma phenotype-associated biomarkers.\n Defining response as improvement in FEV 1 of 7.5% or greater, 17% of 126 participants responded to both medications, 23% responded to fluticasone alone, 5% responded to montelukast alone, and 55% responded to neither medication. Compared with those who responded to neither medication, favorable response to fluticasone alone was associated with higher levels of exhaled nitric oxide, total eosinophil counts, levels of serum IgE, and levels of serum eosinophil cationic protein and lower levels of methacholine PC(20) and pulmonary function; favorable response to montelukast alone was associated with younger age and shorter disease duration. Greater differential response to fluticasone over montelukast was associated with higher bronchodilator use, bronchodilator response, exhaled nitric oxide levels, and eosinophil cationic protein levels and lower methacholine PC(20) and pulmonary function values.\n Response to fluticasone and montelukast vary considerably. Children with low pulmonary function or high levels of markers associated with allergic inflammation should receive ICS therapy. Other children could receive either ICSs or LTRAs.", "Currently available anti-inflammatory treatment for young children with asthma includes inhaled corticosteroids (ICS) and the leukotriene receptor antagonist (LTRA) montelukast.\n To evaluate potential biomarkers of predicting short-term (6-week) response to ICS and LTRAs in children with asthma.\n A total of 102 children aged 4 to 7 years with episodic asthma were enrolled in an open labelled single-centre study. Biomarkers and asthma characteristics were evaluated as predictors of treatment. Of 102 patients 45 became symptomatic during observation and were randomised to treatment either to montelukast or fluticasone for 6 weeks.\n Forced Expiratory Volume in one second (FEV1) increased with both treatments: FEV1 at randomisation was 90.2% and after therapy 106.8% with fluticasone vs. 90.8% and 103.7% for montelukast, respectively, showing that montelukast and fluticasone were equally effective in this age group (p = 0.44). Strong correlations to a favourable treatment response were pre-bronchodilatory FEV1 (p < 0.001) and airway reversibility (p = 0.04) at time of randomisation. None of the other biomarkers (methacholine testing, exhaled nitric oxide [eNO], presence of allergy, total Immunoglobulin E [IgE], cumulative specific IgE, eosinophils and parental smoking) were predictive.\n Despite the small sample size and the open-label design, the study suggests that the use of pre-bronchodilatory FEV1 and airway reversibility appears to be a good indicator of short-term anti-inflammatory therapy in young children with asthma.", "Current guidelines for asthma treatment do not recommend daily maintenance therapy in patients with mild intermittent (step 1) asthma. However, because there is increasing evidence that airway inflammation is present even in this patient group, maintenance anti-inflammatory therapy may be considered. We investigated the clinical impact of regular treatment with the inhaled corticosteroid beclomethasone dipropionate and the leukotriene receptor antagonist pranlukast in the patients concerned. The study was a randomized, controlled, parallel-group, multicenter trial. Eighty-five symptomatic patients with newly diagnosed mild intermittent asthma having normal pulmonary function were assigned beclomethasone or pranlukast for 8 weeks. Then, these medications were stopped for the next 16 weeks. Main outcome measures were asthma symptoms, pulmonary function, and airway inflammation. Treatment with beclomethasone and pranlukast significantly increased forced expiratory volume in 1 second and peak expiratory flow from baseline and decreased asthma symptom scores and sputum eosinophil counts and eosinophil cationic protein contents. After discontinuation of the treatment, symptom scores remained unchanged, but pulmonary function and airway inflammation were aggravated and then returned to the baseline levels. Therefore, maintenance therapy with inhaled corticosteroid or leukotriene receptor antagonist can provide further improvements in asthma symptoms, pulmonary function, and airway inflammation, and discontinuation of the therapy causes worsening of asthma, indicating that stopping or interrupting anti-inflammatory therapy may not be advisable in patients with symptomatic mild intermittent asthma.", "This 6-month, open-label extension study of a previously described base study compared oral montelukast with inhaled beclomethasone in terms of safety, forced expiratory volume in one second (FEV1) measurements, parent and patient satisfaction with treatment, asthma-related medical resource utilization, school absenteeism, and parental work loss in children with asthma. A total of 124 of 266 asthmatic children, 6 to 11 years of age, who enrolled in the base study entered a 6-month open-label extension study (74 boys, 50 girls) and were re-randomized (2:1 ratio) to receive once-daily oral montelukast (n = 83) or inhaled beclomethasone 100 mcg three times daily (n = 41). Children were evaluated in the clinic prior to re-randomization (Month 0) and at regular visits at 1, 3, and 6 months. Children and their parents showed a significantly higher overall satisfaction for montelukast at 6 months than for inhaled beclomethasone (p = 0.001 and p < 0.05, respectively). According to parents, montelukast was more convenient (p < 0.001), less difficult to use (p = 0.005), and was used as instructed more of the time (p = 0.006) compared with beclomethasone. Oral corticosteroid use was similar in the montelukast (13% of patients) and beclomethasone (17%) treatment groups. The montelukast treatment group was more adherent with their regimen than the inhaled beclomethasone treatment group; almost twice as many children on montelukast compared with inhaled beclomethasone were highly compliant (82% versus 45%). The two study groups were similar with respect to overall safety, change in FEV1, asthma-related medical resource utilization, school absenteeism, and parental work loss. Montelukast represents a safe and effective asthma treatment regimen to which children with asthma are more likely to adhere.", "The use of inhaled corticosteroids compared with leukotriene modifying drugs in the treatment of persistent asthma has not been extensively studied.\n To compare the efficacy and safety of a low dose of fluticasone propionate (FP) and zafirlukast in patients previously maintained on inhaled corticosteroids.\n Patients (> or = 12 years old; FEV1 = 60% to 85% of predicted) with persistent asthma who were previously treated with low doses of triamcinolone acetonide (TAA) 400 to 800 microg/day or beclomethasone dipropionate (BDP) 168 to 336 microg/day were randomized to treatment with FP aerosol 88 microg BID (FP, n = 221) or zafirlukast 20 mg BID (n = 216) over 6 weeks.\n Treatment with FP significantly increased the mean change at endpoint (the last post-baseline observation) in FEV1 (0.22 L versus 0.03 L, P < .001), morning PEF (17.8 versus 3.1 L/min, P = .004), evening PEF (16.7 versus 2.6 L/min, P = .002), the percentage of symptom-free days (16.2 versus 7.1%, P = .007), and the percentage of rescue-free days (23.4 versus 9.3%, P < .001), and significantly decreased rescue albuterol use (-0.66 puffs/day versus an increase of 0.27 puffs/day, P < .001) and combined symptom scores (-0.13 versus an increase of 0.08, P < .001) compared with zafirlukast. Treatment with FP maintained the percentage of awakening-free nights (-1.0 +/- 1.0); in contrast, treatment with zafirlukast reduced the percentage of awakening-free nights (-9.0 +/- 1.6, P < .001). A clinically meaningful difference (change of > or = 0.5; P < .001) was observed between FP and zafirlukast in the Asthma Quality of Life Questionnaire (AQLQ) global score and for each domain score except activity limitation (change of 0.3, P < .001). Significantly more patients in the zafirlukast group experienced an asthma exacerbation (n = 14) compared with FP-treated patients (n = 5, P = .035). Patients in the zafirlukast group were significantly more likely to be withdrawn due to lack of efficacy (P < .001).\n Switching patients from low doses of inhaled corticosteroids to a lower total microgram dose of FP improves pulmonary function, asthma symptoms, and quality of life, while switching to the leukotriene receptor antagonist zafirlukast may result in worsening of asthma control. This was indicated by the significant number of zafirlukast-treated patients who were dropped from the study due to lack of efficacy within 6 weeks of discontinuing inhaled corticosteroids.", "Exercise-induced bronchoconstriction occurs in a large proportion of children with asthma, limiting everyday activities important for their physical and social development.\n The purpose of this randomized, double-blind, placebo-controlled study was to compare the ability of different patterns of antiasthmatic treatment, recommended in childhood asthma, to protect patients from exercise-induced bronchoconstriction.\n Children 6 to 18 years of age with atopic asthma were randomized to a 4-week, placebo-controlled, double-blind trial. Patients were randomly allocated to receive daily 200 microg budesonide (twice daily, 100 microg per dose) + 9 microg formoterol (twice daily, 4.5 microg per dose; n = 20); 200 microg budesonide + 5 or 10 mg montelukast (once daily at bedtime; n = 20); 5 or 10 mg montelukast (n = 20); 200 microg budesonide (n = 20); or placebo (n = 20). A standardized treadmill exercise challenge was performed before and after treatment.\n Exercise-induced bronchoconstriction, reflected by area under the curve for the FEV1 values from exercise over the 20-minute period and by maximum percent fall in FEV1 after exercise, was significantly diminished after 4 weeks in all active treatment groups, and compared with placebo. Exercise-induced bronchoconstriction protection improved more significantly in the budesonide + montelukast and montelukast groups compared with other therapeutic options.\n These data indicate differences in effects on exercise-induced bronchoconstriction between therapeutic options recommended in childhood asthma. Control of childhood asthma with exercise-induced bronchoconstriction can be obtained by using regular controller treatment.", "Loratadine added to montelukast has been suggested to improve endpoints of asthma.\n This study investigated the additive effects of concomitant montelukast and loratadine when compared with montelukast, loratadine, and inhaled beclomethasone monotherapies in asthma. Methods. Patients (N = 406) were 15 to 65 years of age with a forced expiratory volume in 1 second (FEV(1))-predicted of 50% to 85%, FEV(1) reversibility > or = 15%, and a minimal level of daytime symptoms and beta -agonist use. This three-part 2X2 crossover-study consisted of two double-blind 6-week treatment periods where patients were administered once daily oral montelukast 10 mg, loratadine 10 mg, montelukast 10 mg + loratadine 10 mg, or twice daily inhaled beclomethasone 200 mu g. A subsequent 48-week extension study compared montelukast + loratadine with beclomethasone. The primary endpoint was the percentage change from baseline in FEV(1).\n Over 6 weeks of double-blind treatment, significant improvements (p < 0.05) in the primary endpoint of FEV(1) were seen for montelukast + loratadine versus loratadine (least-square mean percentage-point difference of 5.8%), beclomethasone versus montelukast + loratadine (2.35%), montelukast versus loratadine (5.94%), and beclomethasone versus montelukast (4.65%); a numerical improvement (p = 0.054) was seen for montelukast + loratadine versus montelukast (1.60%). Significant improvements for montelukast + loratadine versus montelukast were seen in some secondary endpoints (evening peak expiratory flow, nocturnal asthma symptom score, nocturnal awakenings, and asthma-specific quality of life) but not others. Significant improvements in most endpoints except daytime asthma symptoms score were seen for montelukast + loratadine versus loratadine. In the extension study, both montelukast + loratadine and beclomethasone improved several endpoints. All treatments were generally comparable in the percentage of patients with clinical and laboratory adverse experiences.\n In this study, the addition of loratadine to montelukast produced a small numerical, but not statistically significant, improvement in FEV(1) and, in general, no consistent improvement in other asthma endpoints. No improvement of montelukast + loratadine versus beclomethasone was seen in any endpoint." ]

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[ "Laminaria for preinduction cervical ripening.", "Intracervical Foley catheter balloon vs. prostaglandin in preinduction cervical ripening.", "[Cervical ripening : comparison of three methods. Preliminary results of a randomized prospective study].", "Laminaria tents or vaginal prostaglandins for cervical ripening. A comparative trial.", "A comparison of vaginally administered misoprostol with extra-amniotic saline solution infusion for cervical ripening and labor induction.", "Cervical ripening with prostaglandin gel and hygroscopic dilators.", "Preinduction cervical ripening with the Foley catheter and saline infusion vs. cervical dinoprostone.", "Preinduction cervical ripening: prostaglandin E2 gel vs hygroscopic mechanical dilator.", "A randomized trial of misoprostol versus extra-amniotic sodium chloride infusion with oxytocin for induction of labor.", "A randomized trial of extra-amniotic saline infusion versus laminaria for cervical ripening.", "Preinduction cervical ripening techniques compared.", "A comparison of Lamicel and prostaglandin E2 vaginal gel for cervical ripening before induction of labor.", "Extra-amniotic prostaglandin E2 gel vs. amniotomy for elective induction of labour.", "Pre-induction cervical ripening: a randomized comparison of two methods.", "Combining medical and mechanical methods of cervical ripening. Does it increase the likelihood of successful induction of labor?", "Lamicel does not promote induction of labour. A randomized controlled study.", "A randomized trial of misoprostol and extra-amniotic saline infusion for cervical ripening and labor induction.", "Pre-induction cervical ripening: transcervical foley catheter versus intravaginal misoprostol.", "Randomised trial of intravaginal misoprostol and intracervical Foley catheter for cervical ripening and induction of labour.", "Medical and mechanical methods for cervical ripening.", "Low dose intravaginal misoprostol versus intracervical baloon catheter for pre-induction cervical ripening.", "A prospective, randomized comparison of Foley catheter insertion versus intracervical prostaglandin E2 gel for preinduction cervical ripening.", "Cervical ripening: a randomized comparison between intravaginal misoprostol and an intracervical balloon catheter combined with intravaginal dinoprostone.", "A randomized controlled trial comparing vaginal misoprostol versus Foley catheter plus oxytocin for labor induction.", "Hygroscopic cervical dilators and prostaglandin E2 gel for preinduction cervical ripening. A randomized, prospective comparison.", "Induction of labour at term in primigravidae with low Bishop's score: a comparison of three methods.", "A randomized comparison of prostaglandin E2, oxytocin, and the double-balloon device in inducing labor.", "A randomized trial comparing vaginal misoprostol versus Foley catheter with concurrent oxytocin for labor induction in nulliparous women.", "A randomized trial of extra-amniotic saline infusion plus intracervical Foley catheter balloon versus prostaglandin E2 vaginal gel for ripening the cervix and inducing labor in patients with unfavorable cervices.", "Induction of labour in nulliparous women with an unfavourable cervix: a randomised controlled trial comparing double and single balloon catheters and PGE2 gel.", "Induction of labor with three different techniques at 41 weeks of gestation or spontaneous follow-up until 42 weeks in women with definitely unfavorable cervical scores.", "Synthetic laminaria tent for cervical ripening.", "Preinduction cervical ripening. A randomized trial of intravaginal misoprostol alone vs. a combination of transcervical Foley balloon and intravaginal misoprostol.", "A randomized clinical trial comparing vaginal misoprostol versus cervical Foley plus oral misoprostol for cervical ripening and labor induction.", "Extra-amniotic saline, laminaria, or prostaglandin E(2) gel for labor induction with unfavorable cervix: a randomized controlled trial.", "Comparison of extraamniotic Foley catheter and intracervical prostaglandin E gel for preinduction cervical ripening.", "A randomised controlled trial of intravaginal dinoprostone, intravaginal misoprostol and transcervical balloon catheter for labour induction.", "Role of the cervix in the induction of labor.", "A prospective randomized evaluation of a hygroscopic cervical dilator, Dilapan, in the preinduction ripening of patients undergoing induction of labor.", "Trial of extra amniotic saline infusion with oxytocin versus prostaglandin E2 pessary for induction of labor.", "Extraamniotic saline infusion is promising in preparing the cervix for induction of labor.", "A randomized comparison of transcervical Foley catheter to intravaginal misoprostol for preinduction cervical ripening.", "A prospective randomized controlled trial that compared misoprostol, Foley catheter, and combination misoprostol-Foley catheter for labor induction.", "Extra-amniotic saline infusion versus extra-amniotic prostaglandin F2alpha for cervical ripening and induction of labor.", "A randomized trial of prostaglandin E2 gel and extra-amniotic saline infusion with high dose oxytocin for cervical ripening.", "Induction of labour by balloon catheter with extra-amniotic saline infusion (BCEAS): a randomised comparison with PGE2 vaginal pessaries.", "Randomized trial of Dilapan and Laminaria as cervical ripening agents before induction of labor.", "A comparison of three preinduction cervical priming methods: prostaglandin E2 gel, Dilapan S rods and Estradiol gel.", "Comparison of prostaglandin E2 tablets or Foley catheter for labour induction in grand multiparas.", "Cervical ripening and induction of labor with misoprostol, dinoprostone gel, and a Foley catheter: a randomized trial of 3 techniques.", "Cervical ripening and induction of labor with intravaginal misoprostol and Foley catheter cervical traction.", "Cervical ripening: randomized comparison of intravaginal prostaglandin E2 gel with prostaglandin E2 gel plus laminaria tents.", "Preinduction cervical ripening: a comparison of intracervical prostaglandin E2 gel versus the Foley catheter.", "Preinduction use of laminaria for the unripe cervix.", "Cervical ripening before induction of labour in patients with an unfavourable cervix: a comparative randomized study of the Atad Ripener Device, prostaglandin E2 vaginal pessary, and prostaglandin E2 intracervical gel." ]

[ "A controlled, randomized double-blind protocol was used to test the safety and efficacy of Laminaria japonica as a preinduction cervical ripening agent. A 2-day induction with amniotomy on day 2 was allowed. Forty-eight patients were studied including 22 controls. Though laminaria resulted in consistent cervical ripening, it was no better than the control in improving the rate of successful induction. Additionally, the induction time was no shorter with laminaria. There were no demonstrable infections or other adverse sequelae following use of laminaria. For a standard 2-day induction protocol laminaria offered no clear advantage.", "The aim of this study is to compare the effectiveness of the intracervical Foley balloon catheter and 3 mg prostaglandin E(2) tablet(s) in preinduction cervical ripening.\n Ninety women referred to the maternity clinic for induction of labor with a Bishop score of less than or equal to 5 were randomized to receive an intracervical Foley catheter or prostaglandin E(2) tablets. The primary measured outcome was ripening of the cervix as measured with the Bishop score.\n There were no differences in mean Bishop scores between the prostaglandin and the Foley catheter groups. Bishop scores (mean+/-S.D.) after ripening were 6.6+/-0.80 and 6.7+/-0.86 for the Foley catheter and prostaglandin groups, respectively (P=0.54). The Foley catheter group showed a statistically shorter time to ripening compared with the prostaglandin group (3.4+/-2.1 and 6.5+/-3.2 h, respectively (P=0.001). There was no statistically significant difference in induction time (4.8+/-1.8 h and 5.3+/-2.4 h, respectively (P=0.36).\n There are no differences in preinduction cervical ripening efficacy between prostaglandin E(2) and the Foley catheter, but the Foley catheter has the advantage of ripening an unfavorable cervix in a shorter time.", "The authors report the preliminary results of a randomised prospective study begun in April 1992 at the maternity unit of the Caen Regional Hospital group. The aim of the study was to compare the efficacy and tolerability of three methods of cervical ripening in patients at term in whom there was an indication for the induction of labour while local conditions were unfavourable (Bishop score less than 6). In the first group, patients received an intracervical instillation of prostaglandins E2 (Prepidil), in accordance with the usual method of the department. In the patients of the second group, an intracervical Foley catheter with its balloon inflated to 50 cc was inserted and left under traction for 12 hours. Management of patients in the third group consisted of an extraamniotic injection of prostaglandins E2 via a Foley catheter previously inserted into the cervix and the balloon of which was also inflated with 50 cc of sterile water and which was left in place for 12 hours. Regardless of the method, each patient could undergo 3 ripening procedures separated by 24 hour intervals, provided the Bishop score did not reach 6. These results, which concern the first 184 patients enrolled in the protocol show the superior efficacy of the catheter + Prepidil method as compared with the other two (75% success rate after ripening as compared with 50% in each of the other two groups) as well as that intracervical Prepidil is equally effective in terms of success/failure as an intracervical catheter alone.(ABSTRACT TRUNCATED AT 250 WORDS)", "Laminaria tents and vaginal prostaglandin E2 were used to ripen the cervix in a randomly selected group of 20 patients in whom induction of labour was indicated and the Bishop score was less than 5. In the 14 patients who failed to go into labour both methods improved the Bishop score, but the laminaria tents were significantly (P less than 0,02) more effective cervical dilators. The use of laminaria tents in advocated in selected cases.", "The purpose of this study was to compare intravaginal misoprostol with extra-amniotic saline solution infusion with concomitant oxytocin for cervical ripening and labor induction in viable pregnancies.\n Two hundred women with indications for labor induction and unfavorable cervices were assigned randomly to vaginal misoprostol or extra-amniotic saline solution infusion. Twenty-five micrograms of misoprostol was administered every 4 hours up to six doses, followed by intravenous oxytocin administration. Patients who had received extra-amniotic saline solution infusion also received intravenous oxytocin along with a maximum 12-hour saline solution infusion through Foley catheters that were placed above the internal cervical os.\n One hundred women were randomly assigned to misoprostol, and 100 women were assigned randomly to extra-amniotic saline solution infusion. The average interval from start of induction to vaginal delivery was longer in the misoprostol group (1323.3 +/- 700.3 minutes) than in the extra-amniotic saline solution infusion group (970.4 +/- 502.7 minutes; P =.006, log transformed data). Abnormal fetal heart rate tracings were found in 30% of the patients who received misoprostol and in 19% of the patients who received extra-amniotic saline solution infusion (relative risk, 1.6; 95% CI, 1.0-2.4; P =.05). There was more tachysystole in the misoprostol group (8%) than in the extra-amniotic saline solution infusion group (1%; P =.02). There were no differences in the routes of deliveries or neonatal outcomes between groups.\n Extra-amniotic saline solution infusion with oxytocin administration appears more effective and is associated with fewer maternal complications than misoprostol for cervical ripening and labor induction.", "To study the effectiveness and morbidity of adding hygroscopic cervical dilators to prostaglandin gel for cervical ripening and labor induction.\n Patients of at least 34 weeks' gestation with a medical indication for induction of labor and with a modified Bishop score of 5 or less were randomized to receive either prostaglandin gel or prostaglandin gel with hygroscopic cervical dilators. Primary outcomes were time to delivery, change in cervical score, and infection. Secondary outcomes included cesarean delivery rate and deliveries before 24 hours of induction. Continuous variables were analyzed by Wilcoxon sum rank test and categorical data by chi-square or Fisher exact test, with P < 0.05 being significant.\n Seventeen patients were randomized to intracervical prostaglandin alone and 23 patients received intracervical prostaglandin plus hygroscopic dilators. No demographic differences were noted between the groups. After six hours of ripening, the combined group achieved a greater change in Bishop score (3.6 vs. 2.1, P = 0.007) and tended to have a shorter induction time (21.7 vs. 26.4 hours, P = 0.085). The combined therapy group had a higher infection rate than the prostaglandin-only group (59% vs. 12%, P = 0.003).\n Combining cervical dilators with prostaglandin gel provides more effective cervical ripening and a more rapid induction to delivery interval than prostaglandin alone but with a significant and prohibitive rate of infection.", "nan", "To evaluate the efficacy and safety of hygroscopic mechanical dilators (Dilapan) for ripening the pregnant cervix prior to induction of labour at or near term and to compare it with an intracervical PGE2 gel (Prepidil).\n One hundred and eighty-five women (69 nulliparae, 116 multiparae) at term with singleton pregnancies in cephalic presentation, who were scheduled for induction of labour in the labour ward at the National University Hospital, but had an unfavourable cervical score were randomized into 2 groups by random number table. In group 1 (Prepidil), 0.5 mg of PGE2 in 2.5 ml of triacetin gel was inserted into the endocervical canal. In women in group 2 (Dilapan) upto a maximum of 4 hygroscopic dilators were placed in the endocervical canal. If labour did not ensue at the end of 12 hours of ripening, the cervical score was assessed, amniotomy was performed and oxytocin commenced. Neonatal and obstetric outcome was compared, statistical analysis performed using Chi-square, and t-tests.\n Significantly more women in the group who received Dilapan for cervical ripening required amniotomy and oxytocin for induction of labour > 12 hours after priming compared with the group who received Prepidil (p < 0.001). Operative delivery for no progress and fetal distress respectively was similar in the 2 groups. The number of cases of hyperstimulation were higher in the Prepidil group but did not result in an increased incidence of operative deliveries for fetal distress. There was one neonatal death and one case of neonatal sepsis in the Dilapan group. Uterine rupture occurred in 1 woman who received Prepidil.\n Dilapan, a mechanical method of cervical ripening is as effective as the more widely accepted mode of ripening with an endocervical PGE2 gel in achieving vaginal delivery. Dilapan would be useful for cervical priming prior to induction of labour in places where prostaglandins are not available because of cost and the need for a cold chain.", "Our purpose was to compare the efficacy and safety of misoprostol and extra-amniotic sodium chloride infusion with oxytocin for induction of labor. Study Design: This randomized trial compared two methods of labor induction in women requiring cervical ripening. One hundred twenty-three women undergoing labor induction with a Bishop score < or =5 were randomly selected to receive either misoprostol, 50 microg intravaginally every 4 hours, or extra-amniotic sodium chloride infusion. The primary outcome variable was the time interval from induction to vaginal delivery.\n Sixty-one women received extra-amniotic sodium chloride infusion and 62 women received misoprostol. The mean time interval from the start of induction to vaginal delivery was 15.0 +/- 5.0 hours and 16.5 +/- 7.2 hours for the extra-amniotic infusion and misoprostol groups, respectively (P, not significant). The cesarean delivery rate was not significantly different between the 2 groups (32.8% for the extra-amniotic infusion group; 19.4% for the misoprostol group). Maternal and neonatal outcomes were similar between the 2 groups.\n Both methods of induction are equally efficacious and result in similar maternal and neonatal outcomes.", "To compare extra-amniotic saline infusion versus laminaria for cervical ripening and labor induction.\n Patients of at least 34 weeks' gestation with a Bishop score of 3 or less were randomized to either laminaria ripening for 6 hours or more followed by oxytocin induction versus initiation of extra-amniotic saline infusion at the start of oxytocin induction. Indications for induction included 41 weeks' gestation or greater, hypertensive disease, diabetes, oligohydramnios, suspect fetal growth, and nonreassuring fetal testing.\n There were no significant differences in maternal age, race, parity, gestational age, or indications for induction between the two groups (extra-amniotic saline infusion group, n = 26, laminaria group, n = 26). After only 3 hours of oxytocin induction, patients in the extra-amniotic saline infusion group achieved an identical distribution of Bishop scores compared with the patients in the laminaria group after 6 hours or more of pre-induction ripening as well as 3 hours of oxytocin induction. There were no differences in rates of cesarean delivery (extra-amniotic saline infusion 35%, laminaria 35%), infectious complications, or neonatal outcomes between the two groups. The induction-to-delivery interval (+/- standard deviation) was significantly shortened with extra-amniotic saline infusion (extra-amniotic saline infusion 12.9 +/- 5.7 hours versus laminaria 16.9 +/- 7.1 hours, P = .03). In addition, fewer cesarean deliveries were performed for failed inductions (cervix less than 5 cm dilated) in the extra-amniotic saline infusion group (one of 26 versus six of 26, P = .049).\n Extra-amniotic saline infusion offers potential advantages over the use of laminaria. Extra-amniotic saline infusion saves a significant amount of time both by obviating the need for pre-induction cervical ripening and in shortening the induction-to-delivery interval. Also, fewer patients required cesarean delivery for failed induction of labor with extra-amniotic saline infusion.", "To assess the clinical efficacy of pharmacologic, mechanical and combination techniques of cervical ripening.\n From March 1997 to August 1998, all cervical-ripening patients at Lehigh Valley Hospital were randomly assigned to three groups: intravaginal misoprostol, intracervical Foley catheter, or combination prostaglandin E2 (PGE2) gel and Foley catheter. Inclusion criteria included Bishop score < or = 5 and no contraindication to labor. The remaining delivery process was actively managed according to established guidelines. Multiple variables in perinatal outcome were analyzed, with the cesarean section rate and time from ripening to delivery as the main outcome variables.\n Of the 205 patients, 65 were randomized to the misoprostol group, 71 to the Foley group and 69 to the catheter-and-gel group. There were no differences between groups in delivery indications, maternal demographics, ultrasound findings, labor interventions, intrapartum times, mode of delivery, postpartum complications or neonatal outcomes. The misoprostol group demonstrated a higher rate of uterine tachysystole and required oxytocin less when compared to the two catheter groups.\n The higher rate of uterine tachysystole with misoprostol did not increase the cesarean section rate. The higher rate of oxytocin required by the two catheter groups did not increase the delivery time intervals. There appears to be no benefit to adding intracervical or intravaginal PGE2 gel to the intracervical Foley balloon. The misoprostol and catheter ripening techniques have similar safety and efficacy.", "The efficiency and safety of Lamicel, a new synthetic cervical ripening agent, were compared with those of intravaginal prostaglandin E2 gel in a group of 80 primigravid women about to undergo induction of labor. Lamicel caused less uterine activity and fetal distress than prostaglandin gel, although the induction-delivery intervals were similar in both groups. More normal deliveries occurred in the Lamicel group than in the prostaglandin group. It is suggested that Lamicel is a useful, efficient preinduction ripening agent that is safer than intravaginal prostaglandin gel.", "A randomized study was performed to compare three methods of labour induction in 143 clinically normal women (43 nulliparas) at term: amniotomy with or without intravenous oxytocin, extra-amniotic prostaglandin (PG) E2 gel, and extra-amniotic PGE2 gel plus an indwelling catheter. The three methods appeared to be comparable in effect and all of them were perinatally safe. Thus, if preference is given to keeping the ovular sac intact during the early phase of induced labour, extra-amniotic PGE2 in viscous gel, either with or without an indwelling catheter,. can replace the classical induction technique.", "To compare two methods of pre-induction cervical ripening in a randomized clinical trial.\n A single intracervical prostaglandin E2 (PGE2) gel application was compared with a single insertion of hygroscopic dilators in 441 women at term with unfavorable cervical scores. Induction success was defined as entry into active labor within 6 hours of oxytocin infusion.\n There was no statistical difference in pre- or post-ripening cervical scores. In the group receiving hygroscopic dilators, only 28% entered the active phase of labor within 6 hours of oxytocin infusion compared with 45% (P < .001) in the PGE2 group. Thus, in this study, a change in cervical score did not directly predict induction success. There was a higher rate of postpartum endometritis (24 versus 14%; P = .007) and suspected neonatal infection (10 versus 5%; P = .03) in the dilator group.\n Pre-induction ripening by hygroscopic dilators and intracervical PGE2 was equivalent as measured by changes in the cervical score. The change in cervical score, however, was not predictive of successful induction, and PGE2 was more frequently associated with induction success. Hygroscopic dilators were associated with a higher incidence of postpartum maternal and neonatal infection because of a longer duration of labor. Hospital charges for intracervical PGE2 gel totaled $522 compared with $91 for the insertion of three dilators.", "To determine if combining two commonly used methods or cervical ripening (intracervical prostaglandin E2 [Pge2] gel and Foley balloon catheter) would result in a higher number of successful inductions and fewer cesarean sections when compared to PGE2 gel alone.\n Seventy-eight patients with unfavorable cervixes eligible for induction of labor were prospectively randomized to receive either one dose (0.5 mg) of PGE2 gel followed by insertion of a 24-French Foley catheter (group 1, 41 patients) or two doses of 0.5 mg of intracervical gel (group 2, 37 patients). Outcome parameters included change in Bishop score, number of failed inductions, rate of cesarean section, rate of uterine hyperstimulation and postpartum infection.\n Patients in group 1 had a significant increase in posttreatment Bishop scores (7.26 +/- 2.0 SD vs. 4.82 +/- 1.8 P = .0001) and fewer failed inductions (0 vs. 6, P = .009) when compared to patients in group 2. Abdominal delivery rates, uterine hyperstimulation and infections complications were not different between the two groups.\n The combination of the Foley balloon and prostaglandin gel significantly improved the Bishop score and led to fewer failed inductions, although it did not increase the vaginal delivery rate.", "Lamicel is a synthetic tent, which, when inserted in the cervical canal, dilates the cervix by osmosis. Lamicel as an adjunct to induction of labour with intravenous oxytocin or vaginal prostaglandin E2 has been examined in a randomized controlled trial. Ninety-one pregnant women with an unripe cervix participated in the study. No improvement in efficacy was observed in the Lamicel groups compared to the control groups, neither when induction of labour was performed with oxytocin nor with vaginal prostaglandin.", "To compare the cesarean rates in women undergoing induction of labor with unfavorable cervices who receive either misoprostol or extra-amniotic saline infusion.\n We assigned 250 women undergoing indicated induction of labor randomly to misoprostol (50 microg every 4 hours for three doses with or without oxytocin) or extra-amniotic saline infusion and oxytocin. Each eligible subject had a singleton gestation, vertex presentation, intact membranes, cervical dilation no more than 2 cm, and effacement no more than 50%.\n Two hundred forty-eight women were studied after two exclusions; 120 were assigned to misoprostol, and 128 to extra-amniotic saline infusion. This sample size ensured an 80% chance of detecting an intergroup difference in cesarean rates of at least two-fold. The groups were similar in age, race, parity, indication for induction, and gestational age. The extra-amniotic saline infusion group had a significantly lower median initial dilation; however, at 12 hours, this group was significantly more dilated. The groups also were similar in epidural use, chorioamnionitis rates, endometritis rates, birth weights, and neonatal outcomes. Overall, 23% of women underwent cesarean deliveries, 18% and 27% for the misoprostol and extra-amniotic saline infusion groups, respectively (P = .12). There were no significant differences in the median time to either vaginal or cesarean delivery between the two groups. Eighty-one percent of women were delivered in less than 24 hours from initiation of induction; 78% in the misoprostol group, and 84% in the extra-amniotic saline infusion group (P = .19).\n Both methods of labor induction appear to be equally effective in this group of women at high risk for cesarean delivery and prolonged induction of labor.", "The object of this study was to compare the effectiveness of the intravaginal Misoprostol and transcervical Foley catheters as pre-induction cervical ripening agents, to estimate the proportion of patients achieving vaginal delivery and to compare the complications of labour and foetal outcome between the two groups. The study was a prospective, randomised study of pregnant women, with singleton pregnancies who presented for antenatal care and delivery at the University College Hospital (UCH), Ibadan, Nigeria. Ninety-nine patients were invited to participate and ninety-six (96) agreed. No patient withdrew from the study. The patients were assigned by means of computer-generated random numbers to receive transcervical Foley catheters (Size 16F, with 30 ml balloon capacity) or 50 microg intravaginal Misoprostol (Cytotec tablet, Searle & Co., Chicago). Fifty (50) patients received intravaginal Misoprostol and Forty-six (46) received Transcervical Foley catheters. The proportions of nulliparous, primiparous and multiparous patients were 52, 20 and 28% in the misoprostol group and 43.5, 26.1 and 30.4%, respectively, in the Foley catheter group. The time to achieve a favourable cervical status was significantly shorter in the Misoprostol group, with 98.0% of the subjects attaining Bishop score > or = 6 within 6-12 hours of insertion of the study agent, in contrast to 69.0% of the subjects in the Foley catheters group (P<0.001). Thirteen (26.6%) and three (6.5%) patients in the Misoprostol and Foley catheters groups, respectively, went into labour while undergoing cervical ripening and all had uneventful vaginal deliveries (P<0.05). The induction-delivery interval did not differ significantly between the groups. The incidence of caesarean delivery was 6.0% in the Misoprostol group compared with 2.2% in the Foley catheter group (P=0.62). Instrumental vaginal delivery rates were similar in both groups. Overall, the mode of delivery did not differ significantly between the groups. The number of neonates with 1-minute Apgar score <7 did not differ significantly in both groups and no neonate had 5-minute Apgar score <7. Meconium stained liquor was noticed in 5 (Misoprostol) vs 2 (Foley catheters) patients in labour. None of the neonates had any features suggestive of meconium aspiration. Labour complications were mainly precipitate labour {2 (Misoprostol) vs 1 (Foley catheters) } and 1 patient with transient tachysystole (> or =6 contractions in 10 minutes for two consecutive 10-minute periods) in the Misoprostol group. Hyperstimulation was not noticed in any of the patients in either arm of the study groups. Intravaginal Misoprostol is as effective a pre-induction cervical ripening agent as transcervical Foley catheters, with added advantages of shorter duration of cervical ripening, reduced oxytocin requirement for induction of labour and greater acceptability to patients. The incidence of caesarean sections, other labour complications and the foetal outcome were similar with both methods.", "Induction of labour may be indicated despite an unripe cervix. The purpose of this study was to compare the safety and efficacy of intravaginal misoprostol and an intracervical Foley's balloon catheter for preinduction cervical ripening and labour induction. A total of 120 patients requiring indicated induction of labour with an unfavourable cervix (Bishop's score < or =4) were randomised prospectively to receive either 50 mug intravaginal misoprostol every 6 h for a maximum of two doses, or an intracervical Foley balloon catheter for 12 h followed by an intravenous oxytocin infusion. The two arms of the study were comparable with respect to maternal age, parity, gestational age, indication for induction, and initial Bishop's scores. There were significant change in the Bishop's score in the two groups (5.9 +/- 0.2 and 4.0 +/- 0.2, respectively, p < 0.001) but no inter group differences. Oxytocin induction or augmentation of labour occurred more in the catheter group (95%) than in the misoprostol group (43.3%) (p < 0.0001). Induction to delivery interval was significantly shorter in the misoprostol group than in the catheter group (8.7 +/- 2.4 vs 11.9 +/- 2.7 h p < 0.0001). There was no significant difference noted in the caesarean or other operative delivery rates among patients in the two treatment groups. There was a higher incidence of tachysystole and hyperstimulation in the misoprostol group than in the catheter group (p < 0.03). No differences were observed between groups for meconium passage, 1- or 5-min Apgar scores < 7 and admission into the neonatal intensive care unit. In conclusion, the maternal and perinatal outcomes in this study have shown no difference confirming the efficacy and safety of both methods, however we observe a decrease in the induction-to-delivery interval when misoprostol is used for this purpose.", "nan", "The efficacy and safety of low dose misoprostol as a ripening agent compared to the widely used balloon catheter in developing countries is undetermined.\n To compare the safety and efficacy of a low dose intravaginal misoprostol and intracervical Foley's catheter for cervical ripening.\n A prospective randomized controlled trial.\n Zonal General Hospital, Kwale, Nigeria from June 1, 1998 to May 30, 2001.\n Candidates for pre-induction cervical ripening were randomized to receive either 250 mcg of intravaginal misoprostol every four hours (n = 60) or intracervical Foley's catheter (n = 61).\n Failure to achieve cervical ripening within 24 hours, need for augmentation, maternal and foetal complications.\n Failure to achieve cervical ripening within two hours was reduced with misoprostol (Relative Risk [RR] 0.63, 95% Confidence Interval [CI] 0.43 - 0.92). Need for oxytocin augmentation was less in the misoprostol group (RR 0.76, 95% CI 0.64 to 0.91). No significant differences existed in rates for uterine hyperstimulation, Caesarean section, maternal and neonatal morbidity.\n Intravaginal misoprostol in a low dose was compared to intracervical balloon catheter for pre-induction ripening of the cervix.", "The objective of this study was to compare intracervical prostaglandin E2 gel with insertion of a Foley bulb for efficacy in preinduction cervical ripening.\n Women who came to the hospital for induction of labor with a Bishop score </=5 were randomly assigned to treatment with either prostaglandin E2 gel or a Foley bulb. Prostaglandin E2 gel was used according to the manufacturer's recommendation. The Foley group had a number 14 Foley catheter inserted, inflated, and placed on traction. Immediately after Foley bulb extrusion or 6 hours after prostaglandin E2 gel course completion, a dilute oxytocin solution was started if the patient was not in labor.\n Seventy-seven women were entered into the Foley group and 72 were entered into the prostaglandin E2 gel group. Both the Bishop score after preinduction ripening (6.5 vs 5.1, P <.001) and the change in Bishop score (3.5 vs 2.7, P =.015) were significantly higher in the Foley group. There were no differences between the groups in mode of delivery, infant weight, rate of hyperstimulation, shoulder dystocia, patient discomfort, epidural use, oxytocin use, or nonreassuring fetal heart rate patterns. The preinduction time (9.9 vs 17.2 hours, P <.001) and the total induction time (22.4 vs 30.4 hours, P <.001) were significantly shorter in the Foley group. Patient charges were 31% lower in the Foley group (P <.001).\n Use of the Foley catheter resulted in a higher postinduction Bishop score, a greater change in Bishop score, a shorter induction time, and lower patient charges than did intracervical prostaglandin E2 gel.", "Our purpose was to compare the efficacy of intravaginal misoprostol and intracervical Foley catheter/intravaginal dinoprostone for cervical ripening.\n Patients admitted for induction of labor were randomized to receive intravaginal misoprostol 25 microg every 4 hours or intracervical Foley catheter/intravaginal dinoprostone 4 mg every 4 hours. Patients not entering active labor and having ruptured membranes or arrest of dilatation received intravenous oxytocin.\n Sixty-five patients received Foley catheter/dinoprostone gel and 62 patients received misoprostol. The mean time until cervical ripening was less in the catheter/gel group (7.5 +/- 3.4 vs 12.0 +/- 5.9 hours, p < 0.01). The mean time until vaginal delivery was less in the catheter/gel group (17.4 +/- 6.9 vs 21.2 +/- 7.5 hours, p = 0.004). Among vaginal deliveries, more patients in the catheter/gel group delivered within 24 hours (90% vs 69%, p = 0.013).\n Intracervical Foley catheter/intravaginal dinoprostone was associated with more rapid cervical ripening, shorter induction to vaginal delivery interval, and greater number of vaginal deliveries within 24 hours.", "To compare effectiveness and safety of 25 microg vaginal misoprostol versus Foley catheter and oxytocin for cervical ripening and labor induction in pregnant women with unripe cervices.\n Randomized controlled trial.\n A public maternity in Recife, Brazil.\n A total of 240 pregnant women.\n Women with a term or post-term, live, singleton fetus in cephalic presentation, intact membranes, Bishop score <6, not in labor, medically indicated for labor induction. They were randomly divided in Group 1, where 119 women received 25 microg of intravaginal misoprostol every 6 hours for a maximum of four doses; and Group 2, where 121 women had a 14-F Foley catheter inserted into their cervical canal. Once past the internal os, the balloon was inflated. Intravenous oxytocin was initiated after the balloon was spontaneously extruded from the cervix or after 24 hours.\n There were no significant differences between the groups regarding baseline characteristics. Misoprostol was more effective in inducing labor than Foley catheter and oxytocin. Mean induction-to-vaginal delivery time with misoprostol was shorter (17.3 vs. 20.2 hours, p = 0.016). There were more vaginal deliveries in the misoprostol group at 12 (p < 0.001) and 18 (p = 0.007) hours, but the difference was no longer statistically significant at 24 and 48 hours. There were no significant differences in uterine contraction abnormalities, puerperal infection or neonatal outcomes.\n Vaginal misoprostol is more effective than and as safe as Foley catheter and oxytocin for induction of labor in term and post-term pregnancy.", "A randomized, prospective study compared the safety and efficacy of hygroscopic cervical dilators (36 patients) with intracervical prostaglandin E2 (PGE2) gel (38 patients) in preinduction cervical ripening. Maternal age, gestational age and parity were similar in both groups. Both groups had similar cervical Bishop scores upon admission. The change in the cervical score was 3.0 +/- 0.3 (mean +/- SEM) in the dilator group and 2.8 +/- 0.4 in the PGE2 group (P = .7). The mean length of time from amniotomy to delivery was similar in both groups (10.1 +/- 1.0 and 10.3 +/- 1.3 hours, respectively) (P = .9). The proportions of patients in each arm of the study undergoing cesarean section were similar. Eight cesarean sections (21.0%) were performed in the PGE2 group; seven (19.4%) were performed in the dilator group (P = .9). Maternal morbidity, five-minute Apgar scores and admissions to the neonatal intensive care unit were similar in the two groups. Because patients were required to stay in the labor-and-delivery unit for four to six hours of fetal monitoring after PGE2 application, the costs were higher in that group. The dilators and PGE2 gel appear comparable in efficacy as preinduction cervical ripening agents. The need to monitor patients receiving PGE2 gel, however, appears to favor the choice of the dilators from a cost and convenience perspective.", "To determine which of three methods of induction of labour at term in primigravidae with a low Bishop's score is effective and safe.\n Random allocation to Prostin E2 and amniotomy later (Group A); low amniotomy and oxytocin titration (Group B); and intra-cervical Foley balloon overnight followed next morning by low amniotomy and oxytocin titration (Group C).\n Primigravidae (n = 90) in the University Hospitals, Benin City, Nigeria.\n (i) Time taken to achieve 3 uterine contractions in 10 min; (ii) induction-delivery interval.\n The mean time interval between intervention and regular uterine contractions was shortest in Group C (A vs. C, P < 0.02; A vs. B, P < 0.02). The mean induction-delivery interval was shortest in Group C (11.1 h) followed by Group B (13.9 h) and Group C (17.9 h) P < 0.05-0.001.\n The induction-delivery interval was shortest when using a Foley catheter for cervical ripening followed by amniotomy and oxytocin titration.", "To compare the efficacy of three methods for ripening and dilating the unfavorable cervix for induction of labor.\n Pregnant women having an indication for induction of labor with a singleton vertex fetus, intact membranes, and Bishop score of no more than 4 were randomized to one of three induction methods: intravaginal prostaglandin (PG) E2 tablets (3 mg) followed by a second dose if labor did not start; continuous intravenous oxytocin drip; or the Atad Ripener Device, with inflation of both balloons and removal after 12 hours. For all patients, the cervix was assessed by the same investigator before induction and 12 hours later.\n Thirty subjects were included in the PGE2 group, 30 in the oxytocin group, and 35 in the Atad Ripener Device group. The postpartum course was comparable in all. The change in Bishop score in the PGE2 and Atad Ripener Device groups was significantly better than in the oxytocin group (median and range of 5[0-9] and 5[0-7], respectively, versus 2.5 [0-9]; P < .01). Cervical dilation more than 3 cm was more frequent in the Atad Ripener Device group compared with both the PGE2 and oxytocin groups (85.7 versus 50 and 23.3%, respectively; P < .01). The trial of induction failed in only two patients (5.7%) in the Atad Ripener Device group, compared with six (20%) in the PGE2 and 16 (53.3%) in the oxytocin groups (P < .001). Mean (+/- standard deviation) induction-to-delivery interval was 21.3 +/- 7.0 hours in the Atad Ripener Device group, 23.2 +/- 12.5 hours in the PGE2 group, and 28.2 +/- 14.7 hours in the oxytocin group. The success rate for vaginal delivery was significantly better in the Atad Ripener Device and PGE2 groups compared with the oxytocin group (77.1 and 70%, respectively, versus 26.7%; P < .01).\n The Atad Ripener Device had a significantly better success rate for cervical dilation and a lower failure rate than those for PGE2 and oxytocin. The PGE2 and Atad Ripener Device groups had better results than the oxytocin group in regard to Bishop score change and induction-to-delivery interval. The Atad Ripener Device may be a superior method for cervical ripening and labor induction in patients with unfavorable cervices.", "The objective of this study was to compare the efficacy and safety of intracervical Foley catheter with concurrent use of oxytocin versus vaginal misoprostol for labor induction in nulliparous women. Nulliparous women with Bishop score <6 who presented for labor induction were randomized to either 25 microg vaginal misoprostol every 4 hours followed by oxytocin, if indicated, or intracervical Foley catheter with simultaneous use of oxytocin. Among the 162 patients enrolled, 79 (49%) received misoprostol and 83 (51%) received Foley/oxytocin. We were unable to demonstrate a statistically significant difference between the misoprostol group and Foley/oxytocin group in the incidence of cesarean delivery (35% versus 29%; p = 0.37). The induction-to-delivery time was significantly shorter in the Foley/oxytocin group (18 versus 24 hours; p < 0.01). No differences in intrapartum complications, neonatal outcomes, or maternal morbidity were found. When compared with vaginal misoprostol, intracervical Foley catheter combined with oxytocin has a similar efficacy and safety profile for labor induction in nulliparous women. Foley/oxytocin results in a shorter induction-to-vaginal delivery time compared with misoprostol.", "To compare the efficacy of extra-amniotic saline solution infusion plus an intracervical Foley catheter balloon versus 2.85 mg prostaglandin (PG) E2 vaginal gel in ripening the cervix, inducing labor, and achieving vaginal delivery in patients at term with an unfavorable cervix.\n A randomized study of the two methods was performed in 112 patients with a Bishop score of 5 or less.\n Extra-amniotic saline infusion plus intracervical Foley catheter balloon was more effective than PGE2 vaginal gel in causing cervical ripening (relative risk [RR] 2.5965, 95% confidence interval [CI] 1.7277-3.9022, exact two-tailed P = .000001) and in inducing labor (RR 4.3333, 95% CI 1.7223-10.9026, exact two-tailed P = .0000181). However, the final delivery outcome was an equally high number of cesarean deliveries (26 of 56, or 46.4%) for both methods. Maternal and neonatal complications were minimal and not significantly different.\n Extra-amniotic saline infusion with a Foley catheter was more effective than 2.85 mg PGE2 vaginal gel in ripening the cervix and inducing labor. These advantages did not translate into a large number of vaginal deliveries, indicating that factors other than cervical ripening may be responsible for the high incidence of cesarean in patients with an unfavorable cervix.", "To compare the efficacy and patient satisfaction of three methods of labour induction (double balloon catheters, single balloon catheters and prostaglandin gel) in term nulliparous women with unfavourable cervices.\n Randomised controlled trial.\n A total of 330 nulliparous women with unfavourable cervices induced at term.\n Three cervical ripening study arms were used: double balloon catheter (107 women); 16F Foley catheter (110 women) and PGE(2) gel (2 mg) (113 women).\n Caesarean section, induction to delivery interval, adverse reactions and patient satisfaction.\n There was no difference in caesarean delivery rates between groups (double balloon 43%, single balloon 36%, PGE(2) 37%, P = 0.567). The induction to delivery interval was longer in the double balloon group (median 24.5; 95% CI 23.7, 30.6 hours) than the single balloon (23.2; 20.8, 25.8 hours) or PGE(2) (23.8; 21.7, 26.8 hours) (P = 0.043). Uterine hyperstimulation occurred in 14% of the PGE(2) group with none occurring with mechanical cervical ripening. Cord blood gases were worse in the PGE(2) group: median arterial pH double balloon 7.26 (range 7.03-7.40); single balloon 7.26 (7.05-7.44); PGE(2) 7.25 (6.91-7.41) (P = 0.050). Cervical ripening with the single balloon catheter was associated with significantly less pain (pain score > or =4: double balloon 55%, single balloon 36%, PGE(2) 63%, P < 0.001).\n Labour induction in nullipara with unfavourable cervices results in high caesarean delivery rates. Although all methods in this study had similar efficacy, the single balloon catheter offers the best combination of safety and patient comfort.", "To compare the obstetric outcome of induction of labor at 41 weeks and of follow-up until 42 weeks and induction if the patient has still not given birth at 42 weeks.\n Six hundred women at 287+/-1 days of gestation with definitely unfavorable cervical scores were randomized to labor induction (N=300) or spontaneous follow-up (N=300) with twice-weekly nonstress testing and amniotic fluid measurement and once-weekly biophysical scoring. The treatments used in the induction group were (1) vaginal administration of 50 microg misoprostol (n=100), (2) oxytocin induction (n=100), and (3) transcervical insertion of a Foley balloon (n=100). The primary outcome measures were the cesarean delivery rate, whether or not the normal hospital stay had to be extended, and the neonatal outcomes. Secondary outcome measure included number of emergency cesarean deliveries performed for abnormalities of the fetal heart rate (FHR).\n The abdominal delivery rate was 19.3% in the induction group and 22% in the follow-up group (p=0.4). The mean length of hospital stay in the two main groups was 1.4+/-0.8 days and 1.3+/-1 days, respectively (p=0.1). Significantly higher rates of macrosomia and shoulder dystocia were seen in the follow-up group (24.6 and 2.3%) than in the induction group (7.6%, p<0.001; 0.3%, p=0.03). Meconium-stained amniotic fluid and meconium aspiration syndrome were observed significantly less frequently in the induction group (9.3 and 1.3%) than in the follow-up group (20.3%, p<0.001; 4%, p=0.03). Rates of emergency abdominal delivery in response to worrying FHR traces, neonatal intensive care unit admission, and low umblical artery pH were similar in the two groups. There was one intrauterine fetal death in the follow-up group.\n Induction of labor at 41 weeks of gestation does not increase the cesarean delivery rate or cause a longer stay in hospital than follow-up until 42 weeks, and neonatal morbidity is also lower after induction.", "The efficacy and safety of a synthetic laminaria tent (Lamicel; Cabot) in ripening the cervix before induction of labour was compared with prostaglandin E2 (PGE2) oral tablets used intravaginally. Eighty patients were randomly assigned to use of the laminaria tent (N = 40) or PGE2 (N = 40). There were an equal number of primigravidas and multigravidas in each group. The only significant difference between the groups was the higher frequency of uterine hypertonicity (29 v. 5 : PGE2 v. tent) and consequent fetal distress (5 v. 1 : PGE2 v. tent) in the PGE2 group. However, the duration of labour was shorter in the PGE2 group than in the tent group (10, 14 h v. 11,61 h). These findings indicate that the synthetic laminaria tent is the preferred agent for cervical ripening in high-risk pregnancies and in developing countries.", "To determine if the addition of a mechanical ripening agent (transcervical Foley balloon) to a pharmacologic agent (intravaginal misoprostol) improves the efficiency of preinduction cervical ripening.\n Singleton patients with an indication for delivery, unfavorable cervix (Bishop score < or = 5) and no contraindication to labor were randomly assigned to two groups: misoprostol alone (25 micrograms intravaginally every 3 hours for no more than 12 hr) or combination therapy (25-French transcervical Foley balloon inflated to 50 mL of sterile water with identical intravaginal misoprostol dosing). All patients received a history and physical examination (including Bishop score), preripening ultrasound, electronic fetal heart rate and contraction monitoring (to rule out spontaneous labor and document fetal well-being). Multiple variables of perinatal outcome were analyzed, including the main outcome variables of ripening-to-delivery time and cesarean section rate.\n During August 1998 to August 1999, 81 patients were randomized, 40 to misoprostol alone and 41 to combination therapy. There were no differences between the groups with respect to maternal demographics, preripening Bishop score, maternal complications, intrapartum intervention or neonatal outcome. The misoprostol group spent longer periods of time in active labor, and there was a trend for the combination group to require oxytocin for longer intervals. These findings did not significantly affect the total ripening-to-delivery time or cesarean section rate which were similar for both groups.\n The addition of mechanical ripening with a transcervical Foley balloon to intravaginal misoprostol did not improve the efficiency of preinduction cervical ripening. Mechanical and pharmacologic cervical ripening agents appear to act independently rather than synergistically.", "We compared labor induced by vaginal misoprostol versus a supracervical Foley catheter and oral misoprostol. Singleton pregnancies at > or = 24 weeks' gestation were randomized to either an initial 25-microg dose of intravaginal misoprostol, followed by 50-microg intravaginal doses at 3- to 6-hour intervals, or a supracervical Foley balloon and 100 microg of oral misoprostol at 4- to 6-hour intervals. Primary outcome was time from induction to delivery. One hundred twenty-six women were randomized to vaginal misoprostol alone (group I) and 106 women to Foley and oral misoprostol (group II). The groups were similar in age, weight, gestational age, parity, indication for induction of labor, and oxytocin use. Cesarean delivery rates at 37% and cesarean indications were similar ( P = 0.25). The time from induction to delivery in group II (12.9 hours) was significantly shorter than that in group I (17.8 hours, P < 0.001). Uterine tachysystole occurred less often in the vaginal misoprostol group (21% versus 39%, P = 0.015). Compared with vaginal misoprostol, delivery within 24 hours was significantly more likely with a Foley balloon and oral misoprostol. The use of terbutaline and peripartum outcomes were similar in the two groups.", "To determine which of three methods of cervical ripening resulted in the lowest cesarean rate in women with unfavorable cervices and indications for labor induction.\n Consenting women with singleton gestations, vertex presentations, and unfavorable cervices (dilatation under 2 cm and effacement under 75%) were randomly assigned to laminaria and standard intravenous oxytocin, serial doses of intracervical prostaglandin (PG) E(2) gel (Prepidil, Pharmacia & Upjohn, Inc., Kalamazoo, MI) 0.5 microg every 6 hours for two doses followed by oxytocin if indicated, or extra-amniotic saline infusion and oxytocin.\n An interim analysis after recruitment of 321 subjects, 67% of the planned sample, found similar cesarean rates for the three groups (laminaria 36%; PGE(2) gel 33%; saline infusion 29%; P =.59); however, the mean randomization-to-delivery interval was significantly longer in the PGE(2) group. Stochastic curtailment, as part of the interim analysis, indicated a low likelihood of achieving a statistically significant difference in cesarean rates between PGE(2) gel and the other two groups. Therefore, we completed the study with saline infusion and laminaria. The saline infusion and laminaria groups had similar preinduction characteristics. The cesarean rates were similar (saline infusion 25.4% versus laminaria 30.3%; P =.32), but the mean interval from randomization to delivery was shorter in the saline infusion group (18.0 versus 21.5 hours, P =.002). There were no significant differences in selected maternal and neonatal morbidities.\n Cervical ripening with extra-amniotic saline infusion, PGE(2), or laminaria resulted in comparable cesarean rates in women with an unfavorable cervix and indications for labor induction. Extra-amniotic saline infusion had the shortest randomization-to-delivery interval without increasing maternal or neonatal morbidity.", "The success of induced labor depends on the degree of ripening of cervix. Pharmacological preparations are in widespread use for cervical ripening but are not free from side-effects and complications. Mechanical methods, i.e. the use of Foley catheter balloon, though effective have not gained much popularity because of the fear of infection. Therefore, this study has been conducted to prove the efficacy and safety of extraamniotic Foley catheter balloon and to compare it with intracervical prostaglandin E2 (PGE2) gel.\n The randomized prospective study was conducted in the Department of Obstetrics and Gynecology and Medical Microbiology of Nehru Hospital. Hundred women attending the labor ward for induction of labor were divided into two groups: Group A--Foley catheter, Group B--PGE2 gel. Cervical swabs before and after the insertion of ripening agents were taken for culture studies. Placental membranes were also sent for culture. Labor outcome, side-effects, and complications were compared in both the groups. The statistical methods used were Student's compared t-test, Chi-square test, and Wilcoxon-Mann-Whitney test.\n Foley catheter proved to be a very effective preinduction ripening agent for unfavorable cervix compared with PGE2 gel, as is evident by the mean Bishop score at 12 h (P<0.001). Preparation delivery interval was significantly shorter (P<0.05) in women who underwent cervical ripening with Foley catheter balloon than with the PGE2 gel. No clinical evidence of chorioamnionitis was present in both the groups.\n This study concludes that extraamniotic Foley catheter balloon is an effective, safe, simple, low-cost, reversible, non-pharmacological mechanical method of preinduction cervical ripening.", "To compare the efficacy and safety of induction of labour by vaginal application of dinoprostone or misoprostol or transcervical insertion of a balloon (Bard) catheter.\n A non-blinded, randomised, controlled trial.\n A tertiary level Swedish hospital.\n A total of 592 women who had undergone full-term pregnancies, not previously been subjected to a caesarean section, and required induction of labour for common, routine indications.\n Women were randomly assigned to induction of labour using intravaginal dinoprostone (2 mg once every 6 hours) or misoprostol (25 micrograms once every 4 hours) or a transcervical balloon catheter.\n The time interval between induction to delivery in general and vaginal delivery in particular, the mode of delivery, maternal and neonatal parameters of outcome.\n Of the 588 subjects included in the final intention-to-treat analysis, 191 were assigned to treatment with dinoprostone, 199 with misoprostol and 198 with the balloon catheter. The shortest mean induction-to-delivery interval was obtained with the catheter (12.9 hours versus 16.8 and 17.3 hours for dinoprostone and misoprostol, respectively). The efficacies of the two prostaglandins were similar. The maternal and neonatal outcomes associated with each of the three procedures were similar.\n Induction of labour with a transcervical balloon catheter is effective and safe and can be recommended as the first choice. The two prostaglandins, dinoprostone and misoprostol, were shown to be equally effective and safe, while misoprostol costs significantly less and is easier to store.", "A study on induction of labor was carried out to test the hypothesis that changing the cervix will enhance the effectiveness of induction of labor. Fifty pregnant women near term with Bishop scores of 4 or less were divided into 5 study groups, in which a 12-hour preparation phase procedure was carried out to produce cervical or myometrial changes. All women had continuous measurement of uterine activity by an extraovular catheter. The patients were divided into 1) control subjects, and into groups treated with 2) laminaria, 3) Foley catheter, 4) amniotomy, and 5) oxytocin infusion. These preparation techniques were used for 12 hours, after which rupture of membranes was carried out in all cases. Although all procedures significantly changed the cervix, none but oxytocin affected the induction-to-delivery interval. The authors concluded that when a study design rigidly controls for cervical Bishop score, timing of rupture of membranes, and oxytocin infusion rates, the cervical preparation alone will not enhance inducibility.", "Our purpose was to investigate the safety and efficacy of a synthetic intracervical hygroscopic dilator, Dilapan (Gynotech, Inc., Middlesex, N.J.), on ripening the cervix before medically indicated induction of labor.\n Two hundred forty patients with a Bishop score of < or = 4 were prospectively randomized to receive either preinduction synthetic hygroscopic dilators (n = 112) or no pretreatment (n = 128) before oxytocin induction.\n Compared with controls, the dilator group exhibited a significant change in median Bishop score, but there was no significant difference in length of labor (dilator 18.8 +/- 12.8 hours vs control 21.7 +/- 14.8 hours) or in the cesarean section rate (dilator 41/112 [36.6%] vs control 49/128 [38.3%]). Relative proportions of nulliparous and multiparous patients, infant weights, and cervical dilation at the time of cesarean section were not significantly different between groups. No adverse maternal or fetal effects could be attributed to use of the device.\n Preinduction cervical ripening with hygroscopic dilators does not shorten the length of labor or lower the cesarean section rate in patients undergoing induction of labor.", "To determine the effectiveness and safety of cost-effective extra-amniotic saline infusion (EASI) and simultaneous intravenous oxytocin infusion versus prostaglandin E2 vaginal pessary (PGE2) for induction of labor.\n Prospective randomized comparative study.\n Labor room at the Mother and Child Health Centre, PIMS, Islamabad from September 2000 to December 2001.\n Women with singleton alive pregnancies and Bishop score < or =6, requiring induction of labor at > or =37 weeks gestation were randomly assigned to induction either with PGE2 3 mg vaginal pessary in two doses 6 hourly or EASI for 12 hours with simultaneous intravenous oxytocin infusion. Artificial rupture of membranes was done 12 hours post-induction and oxytocin infusion started in PGE2. Main outcome measures were induction delivery interval and the mode of delivery. Secondary outcome measures were the change in modified Bishop score 6 hours postinduction and neonatal outcome in the two induction modes.\n After 4 exclusions, 100 women were recruited in each arm. Mean induction delivery interval was 11.1 and 14.3 hours (p=.00) in PGE2 and EASI respectively. The cesarean rate was 11% and 15% (p=0.4) in PGE2 and EASI respectively. Mean Bishop score at induction was 3.2 in PGE2 and 3.1 in EASI, while after 6 hours it was 4.8 and 6.8 (p=0.00) respectively. Mean APGAR scores at 1 and 10 minutes were identical that is 6.2 and 8.6 respectively.\n Both the modes of induction were equally safe and effective in terms of the mode of delivery and APGAR score. EASI, however, had more rapid cervical ripening and shorter induction delivery interval.", "The application of local prostaglandins before induction of labor in women with an unripe cervix is standard procedure in Sweden. Side effects include uterine hypertonus and occasionally fetal heart rate abnormalities. Failed ripening is reported in up to 25% of cases. A previous report of ripening of the cervix by use of extraamniotic physiologic saline infusion through a Foley catheter applied in the cervix claimed results superior to topical prostaglandins.\n To conduct a prospective randomized trial of extraamniotic saline infusion and intracervical application of dinoprost 0.5 mg on cervical ripening and outcome of labor.\n Eighty-five term singleton pregnant women with unripe cervices where induction of labor was indicated were randomized to prostaglandin or saline infusion after obtaining informed consent. Outcome variables were improvement of cervical score, induction delivery time and mode of delivery.\n The 42 women in the saline infusion group obtained significantly (p < or = 0.001) higher cervical scores and shorter induction delivery intervals (p < or = 0.005) than the 43 women in the prostaglandin group. Cases of unripe cervix after 24 hours were significantly (p < or = 0.01) fewer in the saline group. There were more Cesarean sections in the saline group, but this difference was not significant. Saline infusion did not induce uterine activity and oxytocin was given in every case after the expulsion of the catheter.\n In this study extraamniotic saline infusion was a more efficacious method for ripening of the cervix than intracervical prostaglandin. The absence of early painful contractions is an advantage, but effective stimulation of labor is required to effect delivery after maturation of the cervix.", "To compare the efficacy of intravaginal misoprostol tablets with transcervical Foley catheter for preinduction cervical ripening.\n Pregnant women who presented for induction of labor with unfavorable cervices (Bishop score less than 6) were assigned randomly to intravaginal misoprostol (50 microg tablet every 4 hours for a maximum of six doses) or 30-mL Foley catheter placed transcervically with maintenance of traction.\n Among 111 women, 53 were allocated to misoprostol and 58 to Foley bulb. Contractile abnormalities were more frequent in the misoprostol group (20.4%) than the Foley group (0%) (P <.001). No statistically significant differences were noted between groups in change in Bishop score, preinduction cervical ripening times, and total induction times. There were no statistically significant differences in mode of delivery or adverse neonatal outcomes. Uterine rupture occurred in one woman with two previous cesarean deliveries in the misoprostol group.\n Intravaginal misoprostol and transcervical Foley catheter are equivalent for cervical ripening. Uterine contractile abnormalities and meconium passage are more common with misoprostol.", "The purpose of this study was to determine the efficacy of combination intravaginal misoprostol and intracervical Foley catheter for prelabor cervical ripening.\n A prospective, randomized controlled trial was conducted. Women who were undergoing labor induction, with a singleton gestation >or=28 weeks and an unfavorable cervix (Bishop score <or=6), were assigned to one of three groups: (1) intravaginal misoprostol 25 mug every 3 hours, (2) intracervical 16F Foley catheter, or (3) combination misoprostol-Foley catheter.\n Among 146 patients, 49 patients were assigned to misoprostol, 54 patients were assigned to Foley catheter, and 43 patients were assigned to combination therapy. There was no difference in vaginal delivery rates (misoprostol, 63.3%; Foley, 57.4%; combination, 58.1%; P=.81). There were also no statistically significant differences in the interval between induction to active phase, active phase to delivery, or induction to delivery among the three groups.\n Intravaginal misoprostol and intracervical Foley catheter are comparable for preinduction cervical ripening. The combination of the two methods did not provide additional efficacy.", "To compare the effectiveness of extra-amniotic saline infusion versus extra-amniotic prostaglandin F2alpha for cervical ripening, induction of labor and achievement of vaginal delivery in patients with unfavorable cervices.\n A randomized trial of extra-amniotic saline infusion versus extra-amniotic prostaglandin F2alpha performed at Harare Central Hospital Maternity Unit, Zimbabwe. One hundred and sixty-four patients were recruited from those referred to Harare Central Hospital Maternity Unit who required induction of labor for either maternal or fetal indications.\n 162 patients (extra-amniotic PgF2alpha group, N = 81; extra-amniotic saline infusion group, N = 81) had complete information. Two patients (one from each group) were lost to follow up. The demographic characteristics of the patients and the indications for induction were not statistically different. There was a marginally statistically significant difference in the change of Bishop Score in favor of the extra-amniotic saline infusion (4.0, S.D. = 1.4) as compared to (4.5, S.D. = 1.5) for extra-amniotic PgF2alpha (P value = 0.047). All other parameters showed no statistically significant differences. Maternal and fetal complications were minimal and not significantly different. Extra-amniotic saline infusion was however almost six times cheaper than PgF2alpha.\n Extra-amniotic saline infusion is as effective as PgF2alpha, safe, but much cheaper than PgF2alpha and should be seriously considered as a method of first choice in resource-poor settings.", "Our purpose was to compare the efficacy of extra-amniotic saline infusion plus high dose oxytocin with prostaglandin E2 intracervical gel (Dinoprostone) for preinduction cervical ripening.\n 166 nulliparous women with term pregnancies, vertex presentation, intact membranes and a Bishop score < or = 4 referred for labor induction were randomly assigned to receive a 0.5 mg PGE2 intracervical gel and extra-amniotic saline infusion (EASI) plus high-dose oxytocin. Changes in the Bishop scores, labor progress, various labor end points and outcomes of labor were assessed. Data were analyzed using chi2 analysis or the Student t-test.\n 151 women were studied after 15 exclusions, 75 were assigned to PGE2, and 76 to EASI. The groups were similar in age, race, indication for induction and gestational age. The EASI group had a significant improvement in Bishop score and greater dilation. The mean time to vaginal delivery was 11.4+/-4.8 hours and 18.9+/-6.4 hours for the EASI and PGE2 groups respectively (P=0.001). The cesarean delivery rate was not significantly different between the two groups (25% for the EASI group; 34.6% for the PGE2 group). The cesarean rate due to failure to progress, fetal labor intolerance, and maternal and neonatal outcomes were similar in the two groups.\n Preinduction cervical ripening with EASI plus high dose oxytocin resulted in greater changes in Bishop score, and shorter time to normal vaginal delivery than with PGE2 gel in nulliparous women, without increasing the cesarean rate due to failure to progress or fetal labor intolerance.", "A new method for induction of labour--balloon catheter with extra-amniotic saline infusion (BCEAS)--is evaluated in randomised comparison with prostaglandin E2 (PGE2) in vaginal pessaries.\n One-hundred and nine pregnant women with unfavourable cervices.\n The efficiency of inducing vaginal delivery and the level of 'disadvantages following induction of labour' (DisFIL scorings).\n Overall, BCEAS was less efficient inducing vaginal delivery than vaginal PGE2 (P < 0.01) because of a significant difference among parous women (P < 0.01). In the (larger) primiparous women group, and particularly in the subgroup of these having very low pelvic scores (Lange score, < or = 3), the efficiencies of the two methods were equal (P = 0.06) and P = 0.55, respectively). The levels of DisFIL scorings were not significantly different. However, higher rates of caesarean section followed BCEAS than PGE2 (29% and 10%, respectively; P < 0.05). Serious infectious complications were not recorded following BCEAS. No difference was apparent in the status of the neonates (judging from Apgar scores and umbilical artery pH and SBE). The women, delivering vaginally, commented the two methods equally favourably.\n BCEAS was less efficacious than vaginal PGE2 pessaries, though among primiparous women, especially those with very unfavourable cervices, the difference was not significant. Further refinements of the method are suggested.", "A randomized trial was conducted to evaluate the comparative effectiveness of Dilapan cervical dilators and Laminaria japonicum as cervical ripening agents before induction of labor at term. Patients with Bishop scores of 4 or less and a fetal or maternal indication for induction at 34 or more weeks' gestation were eligible for the study. The outcome variables of interest were Bishop score upon removal of the devices, number of devices used, induction-to-delivery time, and induction-to-complete dilatation time. In the Dilapan group, an average of 4.3 devices per patient was used, compared with 9.7 devices in the laminaria group (P less than .01). Among patients who eventually achieved complete dilatation, the mean (+/- SD) time for the Dilapan group was 10.8 +/- 6.1 hours, compared with 14.7 +/- 9.2 hours with laminaria. For women undergoing induction of labor at term with an unripe cervix, Dilapan appeared to be a preferable alternative to Laminaria japonicum because its use may result in a shorter induction-to-delivery interval with fewer devices required to obtain significant cervical ripening.", "The aim of the study was to evaluate the efficacy of three cervical priming methods. From January 1, 1994 to December 31, 1996 247 patients presenting an indication for induction of labor with an unripe cervix were randomly assigned to one of the following preinduction protocols: 0.5 mg of Prostaglandin E2 gel administered intracervically (n = 83), four hygroscopic Dilapan S rods applied intracervically (n = 82), and 150 mg of Estradiol gel administered intravaginally (n = 82). The inclusion criteria were the patient's informed consent, singleton pregnancy of more than 36 weeks, cephalic presentation, Bishop score < 5 points and reactive non-stress test. If the cervical maturation (Bishop score > or = 5, and/or Bishop score augmentation by 2 points) did not occur after 14 hours of priming, the case was considered a failure. In the opposite case the patient was induced by means of extraamniotic PGE2 administration. The mean gain in the Bishop score was 3.7 points in the PGE2 group 3.9 points in the Dilapan S group, and 2.8 points in the Estradiol group. 71 patients (85.5%) were successfully preinduced in the PGE2 group, 73 (89.0%) in the Dilapan S group, and 63 (76.8%) in the Estradiol group. Labor was induced by preinduction only in 23 patients (31.3%) of the PGE2 group in 17 (20.7%) of the Dilapan S group, and in 14 (17.1%) of the Estradiol group. The mean induction to delivery interval was 7 h 27 min in PGE2 group, 7 h 49 min in the Dilapan S group and 9 h 15 min in the Estradiol group. The Caesarean section rate was 24.4% in the PGE2 group, 10.5% in the Dilapan S group, and 24.4% in the Estradiol group. PGE2 gel and Dilapan S rods proved higher efficacy than Estradiol gel. The highest frequency of labor induced by preinduction only was in the PGE2 group. There were shorter induction to delivery intervals in the PGE2, and Dilapan S groups. The lowest Caesarean section rate was in the Dilapan S group. Neither serious side effects nor negative neonatal outcome were noted in either group.", "The efficacy, safety and outcome of prostaglandin (PG)E2 was compared with Foley catheter for labour induction in grand multiparous women. At a hospital in Jordan, 147 women with Bishop score < or = 5 were randomized to receive 3 mg PGE2 vaginal tablets (n = 75) or 50 mL intracervical Foley catheter (n = 72). The change in Bishop score was significantly higher in the PGE2 group than the catheter group, and time from induction to delivery was significantly shorter in the PGE2 group. Significantly more women needed oxytocin for labour augmentation in the catheter than the PGE2 group and fetal distress was significantly more frequent. For grand multiparas, PGE2 vaginal tablets may be preferable for ripening the cervix as well as for labour induction.", "The purpose of this study was to compare the efficacy of 3 different techniques of cervical ripening and induction.\n Patients who required cervical ripening and induction were randomized to one of 3 groups: (1) supracervical Foley catheter and intravaginal dinoprostone gel, (2) supracervical Foley catheter and 100 microg oral doses of misoprostol, or (3) serial 100-microg oral doses of misoprostol. Intravenous oxytocin was administered when a protraction disorder of labor was identified.\n There were 339 women randomized. There was no significant difference in the time from first intervention to delivery in the 3 groups (P =.546). In each group, a similar percentage of women required oxytocin (P =.103). The rates of cesarean delivery were equivalent among the groups (P =.722). Rates of tachysystole were high but statistically equivalent among the 3 groups. There were no significant differences in Apgar scores or umbilical artery pH.\n Oral 100 microg serial doses of misoprostol, with or without the use of a supracervical Foley catheter, were equivalent to the use of a supracervical Foley catheter and serial 4-mg doses of dinoprostone gel for cervical ripening and the induction of labor.", "nan", "The purpose of this study was to evaluate the efficacy of adding laminaria tents to sequential intravaginal prostaglandin E2 (PGE2) gel for cervical ripening. A prospective, randomized study was conducted from October 1994 to May 1995. Pregnant women with maternal or fetal indications for induction of labor at > or = 37 weeks gestation and a Bishop score of < or = 4 were eligible. Nineteen patients received laminaria tents in addition to 4 mg PGE2 gel, while 25 patients received PGE2 gel alone. After 4 hr, the laminaria tents were removed and the gel was continued in both groups at 4-hr intervals. Induction with oxytocin was initiated after a Bishop score of > or = 5 was achieved. The groups were comparable with respect to maternal age, parity, gestational age, reason for induction, and initial Bishop score. The addition of laminaria tents to sequential PGE2 gel did not statistically improve the time to a favorable cervix (control group 12.7 +/- 8.5 hr (95% CI, 9.1-16.3) and study group 10.9 +/- 7.1 hr (95% CI, 7.5-14.3) (P = 0.59). The 6-hr difference from the time of the initial PGE2 gel placement to delivery was not detected (control group 22.4 +/- 11.2 hr, 95% CI 17-27 and study group 23.4 +/- 13.1 hr, 95% CI 17-29.6 (P = 0.79). The combination approach of laminaria tents and PGE2 gel did not have a significant impact on the vaginal delivery rate, with 28.0% of patients in the control group and 26.3% of patients in the study group undergoing cesarean section (P = 0.90). Maternal and neonatal complications were rare in both groups. We had insufficient evidence to show that the addition of laminaria tents to PGE2 gel improved cervical ripening, the induction to delivery interval, or the cesarean section rate in patients at term undergoing induction of labor.", "Both prostaglandin E2 gel and an intracervical balloon catheter have been shown to be effective for cervical ripening. The purpose of this study is to compare the efficacy of intracervical prostaglandin E2 gel with an intracervical Foley catheter for preinduction cervical ripening.\n A randomized, prospective study was conducted in the Maternity Care Center at the Foothills Hospital at Calgary, Alberta, Canada. Patients with a Bishop score < or = 4 and meeting inclusion and exclusion criteria were included. Thirty patients were randomized to receive prostaglandin E2 gel and 36 to receive an intracervical Foley catheter on the evening before induction. Induction then proceeded the following morning by the preferred method of the attending physician.\n The groups were comparable with respect to maternal age, parity, gestational age, reason for induction, and initial Bishop scores. Both groups had a significant change in Bishop score (4.1 +/- 0.4 and 4.8 +/- 0.5, respectively, p < 0.001); however, there was no significant difference between the groups. There was no significant difference in side effect profile, intrapartum complications, or delivery mode. Six cesarean sections (17.6%) were performed in the Foley group and seven (25%) in the prostaglandin E2 gel group (not significant). The induction-to-delivery interval was 16.0 +/- 1.7 hours in the Foley group and 21.5 +/- 3.2 hours in the prostaglandin E2 gel group (p = 0.014). Apgar scores, cord gases, and neonatal birth weight showed no difference between the groups.\n This study has shown that for preinduction cervical ripening there is no difference in efficacy between intracervical prostaglandin E2 gel or an intracervical Foley catheter.", "nan", "One hundred and nineteen women with singleton pregnancy and cephalic presentation requiring induction of labour in the presence of an unfavourable cervix (Bishop score < or = 4) were studied. Five patients were excluded because of failure to comply with the protocol. Cervical ripening was carried out using 3 different methods; 36 used the Atad Ripener Device, 39 received 0.5 mg PGE2 intracervical gel and 39 received at least one 3 mg PGE2 intravaginal pessary. There were no differences in the demographic characteristics and the indications for induction. Five patients developed complications during the ripening period necessitating intervention; 3 required emergency Caesarean section and 2 delivered vaginally. Although statistically there were no differences among the 3 methods of cervical ripening, the power of the study is probably not large enough to show the differences. The PGE2 pessary appears to be more effective with 68% of patients either going into labour during cervical ripening or succeeding in the cervical ripening compared to around 50% in the Atad and PGE2 gel groups. The vaginal delivery rate was 87.2% in the pessary group compared to 72.2% in the Atad group and 84.6% in the gel group. The duration of labour was also shorter in the pessary group with 73.5% delivered within 24 hours compared to 57.7% in the Atad group and 57.6% in the gel group. Although the results of the Atad device seem to be inferior, the risk of uterine hyperstimulation from the use of the device is probably lower than that of the PGE2 and may therefore be preferable in women with fetuses at high risk of fetal hypoxia." ]

[ "7051984", "4153093", "3890523", "3537596", "1565551", "8436464", "6601256", "8970215", "9109139", "2589274", "7084029", "11163478", "6889154", "5066805", "3935589" ]

[ "Sulphamethoxazole prophylaxis in the otitis-prone child.", "Sulfisoxazole as chemoprophylaxis for recurrent otitis media. A double-blind crossover study in pediatric practice.", "Sulfisoxazole prophylaxis of middle ear effusion and recurrent acute otitis media.", "Prevention of recurrent acute otitis media: chemoprophylaxis versus tympanostomy tubes.", "Efficacy of antimicrobial prophylaxis and of tympanostomy tube insertion for prevention of recurrent acute otitis media: results of a randomized clinical trial.", "Prophylaxis for recurrent acute otitis media: a Brazilian study.", "Sulfisoxazole chemoprophylaxis for frequent otitis media.", "Efficacy of antimicrobial prophylaxis for recurrent middle ear effusion.", "Continuous twice daily or once daily amoxicillin prophylaxis compared with placebo for children with recurrent acute otitis media.", "Prophylaxis of recurrent acute otitis media and middle-ear effusion. Comparison of amoxicillin with sulfamethoxazole and trimethoprim.", "Chemoprophylaxis of recurrent otitis media using trimethoprim/sulfamethoxazole.", "Antimicrobial prophylaxis for infants at risk for recurrent acute otitis media.", "Prophylaxis of otitis media in asthmatic children.", "Otitis media in Alaskan Eskimo children. Prospective evaluation of chemoprophylaxis.", "Recurrent acute otitis media--prophylactic penicillin treatment: a prospective study. Part I." ]

[ "A bedtime dose of sulphamethoxazole was effective in preventing ear infections in otitis-prone young children. Thirty-three such children were studied by means of a random, double-blind, placebo-controlled, cross-over protocol. Nine (27%) of 33 children treated with sulphamethoxazole experienced 10 episodes of acute suppurative otitis media or otitis media with effusion while 19 (58%) of 33 children given a placebo experienced 27 episodes of acute otitis media or otitis media with effusion. No new episode of otitis media was observed in 11 children in whom serial urine samples uniformly had a positive response to Micrococcus lutea bioinhibition test, the method we chose to monitor compliance. Otitis media with effusion (secretory otitis media) was detected less often in the children who were given sulphamethoxazole; this fact suggests that prophylaxis with sulphamethoxazole may prevent persistent middle ear effusion in otitis-prone young children.", "nan", "The efficacy of sulfisoxazole prophylaxis was evaluated in 32 otitis-prone children in a double-blind cross-over clinical trial. During the sulfisoxazole therapy, seven patients (22%) had nine episodes of acute otitis media (AOM) while 20 patients (63%) receiving placebo had 36 episodes of AOM (P = .001). Although sulfisoxazole appeared to be beneficial in patients aged 2 to 5 years, statistically significant efficacy was noted only in children under 2 years of age. Otitis media with effusion persisting for more than five weeks was observed in ten children (31%) during sulfisoxazole therapy and in 14 children (44%) during the placebo period (P greater than .975). Sulfisoxazole therefore appears effective in preventing recurrent symptomatic AOM but not in reducing the frequency of persistent otitis media with effusion. The importance of careful follow-up of children receiving long-term sulfisoxazole therapy for prevention of recurrent AOM is stressed.", "Otitis media has long been recognized as one of the most common diseases of childhood. Several therapeutic modalities have been advocated for the prevention of recurrent episodes of acute otitis media (AOM). A blinded, prospective, randomized study was designed to determine the efficacy of tympanostomy tubes, antibiotic prophylaxis, and placebo. Children with recurrent AOM were entered in the study and followed for at least 6 months. A total of 65 children completed the protocol. Sixty-three of those were under the age of 4 years. Treatment failure was defined as two or more episodes of AOM or otorrhea in less than 3 months. Five of 22 children in the tympanostomy tube group failed, compared to 12 of 20 in the placebo group (p = .02). There were 8 or 21 treatment failures in the sulfisoxazole group. Children with otitis media with effusion (OME) at the time of their initial visit had significantly less middle ear disease when treated with tympanostomy tubes. Tympanostomy tube insertion for prophylaxis of recurrent acute otitis is supported by these findings. Improvement of recurrent AOM was observed in the sulfisoxazole group, but was not statistically significant.", "To determine the efficacy of amoxicillin prophylaxis and of tympanostomy tube insertion in preventing recurrences of acute otitis media, we randomized 264 children 7 to 35 months of age who had a history of recurrent otitis media but were free of middle ear effusion to receive either amoxicillin prophylaxis, bilateral tympanostomy tube insertion or placebo. The average rate of new episodes per child year of either acute otitis media or otorrhea was 0.60 in the amoxicillin group, 1.08 in the placebo group and 1.02 in the tympanostomy tube group (amoxicillin vs. placebo, P less than 0.001; tubes vs. placebo, P = 0.25). The average proportion of time with otitis media of any type was 10.0% in the amoxicillin group, 15.0% in the placebo group and 6.6% in the tympanostomy tube group (amoxicillin vs. placebo, P = 0.03; tubes vs. placebo, P less than 0.001). At the 2-year end point, the rate of attrition was 42.2% in the amoxicillin group, 45.5% in the placebo group and 26.7% in the tympanostomy tube group. Adverse drug reactions occurred in 7.0% of the amoxicillin group and persistent tympanic membrane perforations developed in 3.9% of the tympanostomy tube group. The observed degree of efficacy of amoxicillin prophylaxis and of tympanostomy tube insertion must be viewed in light of the fact that study subjects proved not to have been at as high risk for acute otitis media as had been anticipated and in view of the differential attrition rates.(ABSTRACT TRUNCATED AT 250 WORDS)", "We enrolled 60 children with recurrent acute otitis media (AOM) in a study of the effectiveness of antimicrobial prophylaxis. All children were entered into the study following an acute episode of infection treated with amoxicillin (AMX) for 10 days. Following therapy, the children were re-examined, and then randomly assigned to receive either trimethoprim-sulfamethoxazole (TMP-SMX), amoxicillin (AMX) or a placebo (PLA). Twenty children were included in each group. Each drug was administered once a day at bedtime, at 1/3 the therapeutic dose, for 3 months. Children were re-evaluated with pneumootoscopy during episodes of acute illness and with pneumootoscopy and impedance tympanometry (TYMP) at monthly intervals. We observed a significantly increased rate of recurrent AOM in children receiving placebo compared with those who received antibiotics (50% vs. 17% P < 0.005). Both prophylactic antibiotics were equally effective in preventing recurrent AOM (recurrence rate 20% TMP-SMX, 15% AMX). We also observed that recurrences in children receiving placebo occurred earlier in the study period than in those receiving antibiotics. These results suggest that antimicrobial prophylaxis in children with recurrent acute otitis media is effective in reducing subsequent disease. The similar efficacy of both antibiotics tested suggests that the less expensive agent should be used.", "Sulfisoxazole, 75 mg/kg/d in two divided doses for 3 months, was administered in a double-blind placebo crossover study to 35 children aged 6 months to 5 years who had frequent recurring episodes of otitis media. There was a 40% reduction in the rate of otitis media among patients receiving sulfisoxazole compared with those receiving placebo (0.25 v 0.42 episode per patient-month) which did not depend on age, sex, season, or several other factors. Using a randomized order, among patients who received placebo first, there was a 64% reduction on sulfisoxazole therapy compared with placebo (0.20 v 0.56 episode per patient-month). In this subgroup, there was significant improvement in eustachian tube function according to serial tympanograms. In the patients who received sulfisoxazole first, the rate of acute otitis remained low on placebo (0.28 v 0.30 episode per patient-month), and tympanogram patterns continued to improve after discontinuation of the active drug. These differences suggest a carry-over effect from the benefits of chemoprophylaxis. There was no significant difference in the species or sensitivity patterns of bacteria isolated from patients receiving sulisoxazole or placebo. Sulfisoxazole chemoprophylaxis appears to be safe and effective in significantly reducing episodes of otitis media and improving tympanogram patterns.", "This trial compared the efficacy of amoxicillin prophylaxis with that of placebo for the management of recurrent middle ear effusion (MEE) in children.\n Children between 7 months and 12 years of age who were effusion-free at entry but had histories of chronic or recurrent MEE were randomly assigned to receive either amoxicillin (20 mg/kg once daily) or placebo for 1 year. They were examined monthly and when there were symptoms of ear, nose or throat disease. Acute otitis media (AOM) and new episodes of otitis media with effusion (OME) were treated with amoxicillin-clavulanate; tympanocentesis was performed when possible for episodes of AOM. Throat cultures were obtained at entry; 4, 8 and 12 months after entry; and with new episodes of AOM and OME. Tympanometry was performed at each visit and audiometry was performed at entry and 4, 8 and 12 months after entry.\n One hundred eleven children were entered in this study. The rates per person year of new episodes of disease in the amoxicillin and placebo groups, respectively, were: MEE, 1.81 vs. 3.18 (P < 0.001); AOM, 0.28 vs. 1.04 (P < 0.001); and OME, 1.53 vs. 2.15 (P = 0.016). Subjects in the amoxicillin group had less time with MEE than the placebo group (19.7 and 33.2%, respectively; P = 0.002). Middle ear and throat cultures did not reveal any increase in beta-lactamase-producing organisms or in Streptococcus pneumoniae attributable to daily use of amoxicillin.\n Amoxicillin prophylaxis lowered the rates of occurrence of MEE, AOM and OME and decreased the percentage of time with MEE. However, because of present day concerns regarding antibiotic resistance, management should be individualized.", "To determine the effectiveness of amoxicillin administered continuously twice daily vs. once daily vs. placebo to prevent new episodes of acute otitis media (AOM).\n Randomized, double blind, placebo-controlled clinical trial at a hospital-based general pediatric clinic and a private pediatric practice, both in Denver, CO.\n One hundred ninety-four children (age 3 months through 6 years) were enrolled with 3 documented AOM episodes within the prior 6 months, without ventilating tubes or associated anatomic defects, immunodeficiency disorders or allergy to penicillin. Thirty-six were noncompliant and were excluded from the study, leaving 158 evaluable subjects.\n The amoxicillin dosage was 20 mg/kg/day either bid or qd. After randomization to placebo twice daily (bid), amoxicillin once daily (qd)/placebo qd or amoxicillin bid, patients were followed monthly and were also seen for upper respiratory infection symptoms during enrollment in the trial. Development of two new AOM episodes terminated the patients from the study.\n Incidence density (ID) measurements were calculated for all study subjects and were stratified by age and season. Overall study subjects in all 3 arms of the trial had 7243 days at risk during which time they developed 56 new AOM episodes for a annual ID of 2.82. There were no significant differences in the IDs between amoxicillin qd vs. bid or amoxicillin (bid or qd) vs. placebo. After stratifying by age and season of enrollment, there were no significant differences in ID rates among the 3 groups. The proportion of subjects remaining otitis-free was 63% for the placebo group, 64% for once daily amoxicillin and 61% for twice daily amoxicillin.\n While once-a-day dosing was equivalent to twice-a-day dosing for amoxicillin prophylaxis, there was no benefit of amoxicillin prophylaxis compared with a placebo control in preventing new AOM episodes. Because of the potential of excessive antibiotic use to promote the acquisition of resistant pneumococci and the lack of effectiveness in this trial, routine use of amoxicillin prophylaxis should be discouraged.", "We compared the efficacy of amoxicillin with that of the combination drug sulfamethoxazole and trimethoprim in reducing recurrences of acute otitis media (AOM) in a single-blind, randomized, placebo-controlled trial involving 96 children. Each of the children had had three or more episodes of AOM in the preceding 6 months, and 97% (93/96) of them still had unilateral or bilateral effusion at the beginning of the study. During the 6-month study period, 9 (27%) of 33 of the children in the amoxicillin group developed 9 episodes of AOM, 9 (27%) of 33 of the children in the sulfamethoxazole and trimethoprim group experienced 11 episodes of AOM, and 19 (63%) of 30 of the children in the placebo group developed 25 episodes. Young age and day-care attendance characterized children for whom prophylaxis was more efficacious. Overall persistence of middle-ear effusion was shorter in treated children only as a consequence of the reduced number of new episodes of AOM.", "This study was undertaken during the late fall, winter, and early spring months to determine the efficacy of daily trimethoprim/sulfamethoxazole (TMP/SMX) administration in the prevention of recurrent acute otitis media (RAOM) in a specific high-risk pediatric population. Twenty-one ambulatory patients, 10 in the study group and 11 in the control group, were selected from a medical university clinic and a local private practice. The study group receiving prophylactic therapy for six months suffered no recurrences, as compared with eight children suffering one recurrence each in the control group that was treated only acutely. The results were significant at p less than 0.005 with df = 1, determined by the Fischer's exact test and the chi-square method using Yates's correction factor. These data indicated that a mean dose of TMP/SMX 6.8/34 mg/kg/d divided into twice daily doses and given for six months was safe and effective in controlling RAOM infections in a high-risk pediatric population.", "nan", "Seventy-two asthmatic children with recurrent otitis media were studied over a 2-year interval. They were randomly divided to receive either (1) no routine medication, (2) antihistamines whenever nasally congested, (3) daily sulfisoxazole at 500 mg twice a day, (4) pneumococcal immunization and (5) both pneumococcal vaccine and 500 mg sulfisoxazole twice daily. There was no apparent benefit in the antihistamine group. There was a mean yearly reduction in otitis media of 75% in the sulfisoxazole group, 38% in the pneumococcal vaccine group and 90% in the group treated with both agents. The latter group also had a 56% reduction in frequency of acute asthmatic attacks and a 90% decrease in hospitalizations associated with otitis media. In conclusion the use of sulfisoxazole and pneumococcal vaccine appears efficacious for management of asthmatic children with recurrent otitis media.", "nan", "Recurrent acute otitis media (RAOM) is a distressing clinical manifestation of middle ear pathology, mainly expressed in the first two years of life. In this controlled study, prophylactic treatment by phenoxymethyl penicillin reduced significantly the frequency of RAOM in 60 children, as compared to 48 children who received a short ampicillin course only on the occasion of an acute otitis media episode. The importance of breastfeeding, age at initial episode, the type of treatment given and the pertinent literature is discussed. A working hypothesis of this prophylactic treatment is suggested." ]

[ "12521500", "9442160", "894653", "9662313", "9790365", "12118640", "10642965", "8677083", "8735733", "8217970", "1637758", "9086420", "10828706", "10410476", "2216203", "9509948", "2213744", "9442159", "8649700" ]

[ "The role of membrane stripping in prevention of post-term pregnancy: a randomised clinical trial in Ile-lfe, Nigeria.", "Sweeping of the membranes at 39 weeks in nulliparous women: a randomised controlled trial.", "Membrane stripping to induce labor.", "Management of pregnancies beyond forty-one weeks' gestation with an unfavorable cervix.", "Can we decrease postdatism in women with an unfavorable cervix and a negative fetal fibronectin test result at term by serial membrane sweeping?", "Does sweeping of membranes beyond 40 weeks reduce the need for formal induction of labour?", "Membrane sweeping versus dinoprostone vaginal insert in the management of pregnancies beyond 41 weeks with an unfavorable cervix.", "A randomized controlled trial of membrane stripping at term to promote labor.", "Stretching of the cervix and stripping of the membranes at term: a randomised controlled study.", "Sweeping the membranes: a valid procedure in stimulating the onset of labour?", "Sweeping of the membranes is an effective method of induction of labour in prolonged pregnancy: a report of a randomized trial.", "Outpatient management of the uncomplicated postdate pregnancy with intravaginal prostaglandin E2 gel and membrane stripping.", "Sweeping of the membranes versus uterine stimulation by oxytocin in nulliparous women. A randomized controlled trial.", "A comparative study of membrane stripping and nonstripping for induction of labor in uncomplicated term pregnancy.", "Stripping membranes at term: can it safely reduce the incidence of post-term pregnancies?", "Safety and efficacy of stripping of membranes at term.", "Stripping the fetal membranes at term. Is the procedure safe and efficacious?", "Does sweeping of the membranes reduce the need for formal induction of labour? A randomised controlled trial.", "Stripping of membranes as a safe method to reduce prolonged pregnancies." ]

[ "This study was carried out to evaluate the efficacy and safety of membrane stripping at term in reducing the incidence of post-term (41 weeks or greater) pregnancies. One hundred and thirty-seven pregnant women at 38 weeks gestation were randomised to receive either membrane stripping (69) or gentle cervical examination (68). Women who received stripping had earlier delivery (4.8 vs. 12.1 days; P<0.001) and less incidence of delivery at 41 weeks or greater (3% vs. 16%; P=0.009). No statistically significant difference was noted in incidence of premature rupture of membranes, clinical evidence of chorioamnionitis, intrapartum characteristics and perinatal outcome. We conclude that membrane stripping is a safe method to reduce the incidence of post-term pregnancy.", "To determine whether weekly sweeping of the membranes from 39 weeks of gestation results in a reduction in the number of women reaching 41 completed weeks and subsequently in a reduction of the number of women who will need induction of labour.\n Randomised controlled trial.\n Two hundred and seventy-eight nulliparous women, who were seen at the antenatal clinic of a university teaching hospital, were randomly allocated at 39 weeks of gestation to receive on a weekly basis either sweeping of the membranes (n = 140) or a routine pelvic examination (n = 138).\n The time interval between randomisation and delivery, the incidence of prolonged pregnancy (i.e. > 41 completed weeks), and the incidence of induction of labour.\n In 24 women (17%) sweeping of the membranes was not possible. Fifty-three women (38%) in the sweeping group and 50 women (36%) in the control group were delivered within one week after randomisation. Women allocated to sweeping showed a trend towards having a shorter randomisation-delivery interval: 9.4 days versus 10.6 days in the controls (P = 0.087). Sweeping had no statistically significant effect on the mean duration of pregnancy (282.8 days in the sweeping group versus 283.8 days in the control group, P = 0.127). The need for induction of labour was significantly reduced in those women who underwent sweeping (11% versus 26%, P = 0.004), merely as a result of a decrease in the number of women that exceeded 41 weeks (19% versus 33%, P = 0.016).\n Sweeping of the membranes weekly from 39 weeks does not increase the number of women who will deliver within the first week but significantly decreases the number that will reach 41 weeks. Induction of labour then becomes less necessary.", "A group of 91 pregnant women at term were studied randomly to see the effect of digital stripping of the membranes from the lower uterine segment upon the onset of labor. The women with unfavorable cervices (Bishop score 0 to 5) demonstrated a significant increase in the onset of labor within 48 hours as compared to controls. When the cervix was favorable (Bishop score 6 to 10), there was no significant effect. The overall success rate for induction of labor was not significantly altered (43.5% in membrane-stripped patients, 22.2% in controls). There were no major complications of the procedure.", "Our purpose was to determine the optimal management of pregnancies beyond 41 weeks' gestation with a cervix unfavorable for induction.\n All uncomplicated pregnancies that reached 41 weeks' gestation with a Bishop score of < or = 4 were randomly assigned to one of three groups: (1) daily cervical examinations, (2) daily membrane stripping, or (3) daily placement of prostaglandin gel until 42 weeks.\n In 105 pregnancies the Bishop score on admission to labor and delivery was significantly greater in the groups receiving prostaglandin or stripping of the membranes versus the control group, whereas the converse was time of gestational age at delivery (p = 0.0001). Fewer patients required induction in the two treatment groups (20%, 17%) versus the control (69%) patients (p < 0.0001).\n Daily membrane stripping or daily placement of prostaglandin gel is successful in reducing the number of inductions at 42 weeks for postdatism.", "Our purpose was to determine whether the risk for postdatism can be reduced by serial membrane sweeping in women with an unfavorable cervix at 39 weeks' gestation and a negative fetal fibronectin test result.\n Women with uncomplicated pregnancies, who were candidates for a vaginal delivery with an unfavorable cervix at 39 weeks' gestation and a negative fetal fibronectin test result were asked to participate in this investigation. Patients were chosen at random and assigned to a group for membrane sweeping every 3 days or to a control group who received gentle examinations every 3 days.\n Sixty-five women were selected at random for serial membrane sweeping (n = 33) or for the control group (n = 32). Although gestational age and Bishop score at study entry were similar, the gestational age on admission for delivery was earlier in the membrane sweeping group (39.9 +/- 0.3) versus the control group (41.5 +/- 0.6, P < .0001). The Bishop score on admission to labor and delivery was greater (8.8 +/- 2.1) in the membrane sweeping group than in the control group (6.2 +/- 2.7, P < .0001). The number of women admitted for labor inductions at 42 weeks' gestation was 18 of 32 (56%) in the control group versus none (0 of 24) in the membrane-sweeping group (P < .0001).\n Women with an unfavorable cervix at 39 weeks' gestation and a negative fetal fibronectin test result are at risk for not being delivered by 41 completed weeks and thus may require postdates induction or antenatal testing. Serial membrane sweeping significantly reduces the risk of postdatism and induction of labor.", "To assess the efficacy of sweeping of membranes beyond 40 weeks of gestation in reducing the incidence of induction of labour, when induction was planned at 42 weeks.\n Prospective randomised controlled trial.\n A regional obstetric unit in Hong Kong.\n A total of 120 women with certain gestational age, determined by early pregnancy ultrasound scan, were recruited from 1st July, 1998 to 31st December, 1999. Sixty women were randomly allocated to sweeping of membranes and the other 60 women acted as control. The satisfaction for women allocated to sweeping of membranes was assessed by a questionnaire after the procedure. The two groups were assessed on intention-to-treat basis.\n The incidence of formal induction of labour was compared between the two groups. Possible complications of sweeping of membranes such as rupture of membranes, intrapartum infection, postpartum infection, and neonatal infection were also assessed. Maternal and perinatal outcomes were also assessed.\n The recruitment to delivery interval was significantly shorter among women who had sweeping of membranes (3.2 versus 4.2 days, P < 0.05). The incidence of induction of labour was comparable (35.5% versus 38%, RR 0.91, 95% CI 0.57 - 1.46). The incidences of caesarean section and assisted vaginal delivery were comparable. The incidences of premature rupture of membranes, intrapartum, and postpartum infection were comparable. The perinatal outcomes were also comparable between the two groups. Up to 70% of women found that this procedure was associated with significant discomfort. One third of these women complained of significant pain.\n Sweeping of membranes beyond 40 weeks does not reduce the need for formal induction of labour at 42 weeks. Although it is safe, the majority of women felt uncomfortable during the procedure.", "To determine the best method of cervical ripening to prevent postdate inductions in women with an unfavorable cervix at 41 weeks' gestation.\n Women presenting at 41 weeks' gestation with a Bishop score of < or = 4 received daily dinoprostone (Cervidil) vaginal inserts (group I) or daily membrane sweeping (group II).\n One-hundred and eighty-two women were prospectively randomized with 91 women in each arm. The women in group II, membrane sweeping, had Bishop scores significantly greater on admission for delivery (p < 0.001), had less time elapsed from admission to delivery (p = 0.018), and had fewer labor inductions at 42 weeks (p = 0.04) than the women in group I, the dinoprostone group. In addition, a greater number of women in group II were admitted in spontaneous labor (p = 0.006) than in group I. Total antenatal costs for the membrane sweeping group was $15,120 versus $59,540 for the dinoprostone group.\n Daily membrane sweeping was more effective than dinoprostone administration with fewer postdate inductions at one-fourth the cost.", "To determine the effectiveness of membrane stripping at term to promote the onset of labor.\n One hundred twenty gravidas at 38 weeks' gestation, who were attending an antenatal clinic and planned to deliver at Maharaj Nakorn Chiang Mai University Hospital in northern Thailand, were assigned randomly to one of two groups. One group had weekly pelvic examinations only, and the other also had membrane stripping, beginning at 38 weeks' gestation and continuing until the onset of labor or until 42 completed weeks' gestation. Outcome measures included the proportion of patients who delivered with 7 days after the first examination, Bishop scores among those who did not deliver, days from the first examination to delivery, incidence of postterm pregnancy, and maternal and fetal complication.\n Twenty-five of 61 patients (41%) assigned to membrane stripping delivered within 1 week, compared with 12 of 59 controls (20.3%), a statistically significant difference (P = .014). There was also a statistically significant difference (P = .013, Mann-Whitney U test) in the Bishop scores among those who did not deliver within 1 week (4 +/- 2.5 versus 2.6 +/- 1.7 in the study and control groups, respectively). A significant difference was also observed with respect to the mean number of days to delivery (8.8 +/- 6.7 versus 13.6 +/- 7.5, respectively; P < .001). The incidence of postterm pregnancy was one of 61 (1.6%) and three of 59 (5.1%) in the stripping and control groups, respectively. No significant differences were observed in maternal and fetal complications.\n Membrane stripping is safe and effective in promoting the onset of labor at term.", "To determine whether routine antepartum stretching of the cervix and stripping of the membranes at term would shorten the length of pregnancies, and whether this correlated with cervical status and fetal and maternal parameters.\n A prospective, randomised, controlled study of 293 term gravidas, free of medical complications, divided into two groups: stretching/stripping, and non-stretching/stripping. Digital separation of the fetal membranes from the lower uterine segment, and cervical stretching, were performed during routine vaginal examination of the first group. In the second group, only routine vaginal examination was performed.\n Of 293 patients, 152 underwent a trial of stretching and stripping; 141 served as a control group. The mean interval (hours to delivery after the procedure) was 136 h (S.D. 10), compared to 161 h (S.D. 11) in the control group (P = 0.095; not significant), but with only a trend towards the shorter interval in the first group. When patients were matched according to weeks of gestation and fetal and maternal parameters, only those at 41 weeks' gestation or more had a significant reduction in the interval from the procedure to delivery (mean 91 h (S.D. 8) compared to mean 125 h (S.D. 10) in the control group; P < 0.007). This observation was independent of cervical status and other maternal or fetal parameters.\n Only patients > or = 41 weeks' gestation benefitted from stretching of the cervix and stripping of the fetal membranes. The effect was not dependent on the cervical status or other maternal and fetal parameters.", "To determine whether sweeping the membranes in pregnancies of longer than 40 weeks gestation results in an accelerated onset of labour and a reduction in the incidence of induction of labour.\n A prospective randomised controlled study.\n The antenatal clinic of a district general hospital.\n One hundred and ninety-five antenatal women with pregnancies proceeding beyond 40 weeks gestation.\n A Bishop score assessment of the cervix alone or combined with a membrane sweep, on a randomised basis.\n Subsequent duration of pregnancy to the onset of spontaneous labour. The incidence of induction of labour for post-maturity.\n Sweeping the membranes significantly reduces the subsequent duration of pregnancy, from an average of five days to two days following the procedure. The proportion of inductions of labour was 8.1% in the swept group and 18.8% in the control group. No harmful side effects to the procedure were noted.\n Sweeping the membranes is a safe and useful procedure which results in a reduced incidence of post-mature pregnancies, and a subsequent reduction in the labour induction rate.", "To determine whether sweeping of the membranes is an effective method of induction of labour in women with prolonged pregnancy.\n Randomized controlled trial.\n A district maternity hospital.\n 65 women attending an antenatal clinic; 33 randomized to sweeping of the membranes and 32 to a control group.\n Proportion of women achieving spontaneous labour.\n Spontaneous labour occurred more often in the sweeping of the membranes group than in the control group (25/33 (76%) vs 12/32 (38%); odds ratio (OR) 4.65; 95% confidence interval (CI) 1.75 to 12.31; P = 0.002). In addition a greater proportion of women in the sweeping group had a cervical dilatation of 4 cm or more at the first vaginal examination in the labour ward (16/33 (49%) vs 5/32 (16%); OR 4.39; 95% CI 1.56 to 12.32; P = 0.005). There were fewer maternal infections in the sweeping group (0/33 vs 4/32 (12%); OR 0.12; 95% CI 0.02 to 0.88; P = 0.04). There were no differences in the type of analgesia used in labour, the mode of delivery or neonatal outcome.\n Sweeping of the membranes is an effective method of induction of labour in women with prolonged pregnancy.", "The purpose of the study was to determine the safety and efficacy of outpatient intravaginal prostaglandin E2 (PGE2) and membrane stripping in promoting labor in the uncomplicated postdate pregnancy. In a double-blind placebo-controlled study, 150 enrollees were randomized to one of four treatment groups; group I, no membrane stripping and placebo gel; group II, no membrane stripping and PGE2 gel; group III, membrane stripping and placebo gel; and group IV, membrane stripping and PGE2 gel. The treatments were administered at 287 days (41 weeks) and 294 days (42 weeks) of gestation, then every 3-4 days until 307 days (43 completed weeks) of gestation. The patients in group IV had the shortest interval to delivery with a median of 1 day, P = .001, and the fewest antenatal surveillance visits with only 21% requiring more than one visit, P = .02. Group I patients in comparison, had a 7-day median to delivery, and 61% required more than one visit. The time spent in labor and delivery and the need for oxytocin augmentation was not significantly reduced in groups II, III, and IV. No adverse side effects to either mother or neonate could be directly attributed to this outpatient treatment combination. We conclude that intravaginal PGE2 gel combined with membrane stripping reduces postterm pregnancies and antenatal visits in our patients.", "The aim of this study was to evaluate whether sweeping of the membranes at term could shorten the length of pregnancy and reduce the incidence of postterm pregnancies. We randomly selected 104 nulliparas with uncomplicated pregnancy and gestational age between 281 and 287 days. Our patients were divided into three groups. Group A consisted of 34 women who were subjected to sweeping of the membranes. Uterine stimulation with oxytocin was applied in 35 women (group B), and 35 women (group C) were used as a control group. We had no significant reduction of the time interval from sweeping of the membranes until delivery (1.9 +/- 1.2 days), compared to that of group B (2.1 +/- 0.8 days) as well as that of the control group (2.5 +/- 0.9 days). The incidence of spontaneous labor in patients after sweeping of the membranes was greater (67.6%) when compared with oxytocin-stimulated patients and the control group (p < 0.05). Furthermore, a better Bishop score was noted in patients of group A. No statistically significant difference was noted in the mode of delivery between the groups, but sweeping of the membranes significantly decreased the incidence of postterm pregnancies (p < 0. 05). We concluded that sweeping of the membranes is an effective method for initiating labor in women with a gestational age between 40 and 41 weeks, thus reducing the need for induction.\n Copyright 2000 S. Karger AG, Basel", "A prospective, randomized controlled trial was undertaken at the Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn Hospital to determine whether stripping of the fetal membranes is a safe and effective method for induction of labor in uncomplicated term pregnancy. Ninety-six women were included in this study; 16 were excluded; 41 were randomized to a study group and 39 to a control group. Both groups had pelvic examination performed under sterile technique and a Bishop score was assessed. In the study group, membrane stripping was performed. Gentle pelvic examination for Bishop scoring was continued weekly in both groups. Thirty five of 41 women (85.4%) in the study group delivered within 7 days as compared to 22 of 39 women (56.4%) in the control group, a statistically significant difference (P = 0.004). A statistically significant difference was also observed with respect to the mean number of days to delivery (5.3 +/- 4.9 versus 9.5 +/- 5.9 days, respectively; P = 0.002). No statistically significant differences were observed in both maternal and fetal complications. In conclusion, membrane stripping is a safe and effective method for induction of labor in uncomplicated term pregnancy.", "Membrane stripping has been used clinically for many years but has not been well studied. An investigation was undertaken to determine whether weekly membrane stripping beginning at 38 weeks could safely reduce post-term pregnancies. One hundred eighty patients with firm gestational dates were randomized to either a treatment or control group. Control subjects received a gentle cervicovaginal examination each week to assess Bishop scores, whereas the treatment group also underwent weekly stripping of membranes. Women who received treatment had earlier delivery (mean +/- SEM 8.60 +/- 0.74 versus 15.14 +/- 0.83 days; P less than .0001) and fewer post-term deliveries than those in the control group (three versus 14; P less than .004). The reduction of post-term pregnancies was most notable in nulliparous women with unfavorable Bishop scores. Complications were similar in both groups. Membrane stripping was safe and was associated with earlier delivery and a decreased incidence of post-term gestation.", "To assess the efficacy of stripping of membranes in initiation of labor and to study its effect on maternal and perinatal morbidity.\n One-hundred primigravidae with certain gestational dates were randomized at 38 weeks gestation to either receive stripping of membranes or only gentle cervical examination. Cervical swabs were taken before pelvic examination at 38 weeks and again at the onset of labor. Placental membranes were sent for bacteriological study after delivery in all patients.\n The mean gestational age, parity and Bishop score were similar in both groups at recruitment. Gestational age at delivery was lower in the study group (38.70 +/- 0.63) compared to the control group. Seventy-two percent of the study group and 8% of the control group had spontaneous onset of labor within 7 days of examination. Labor was induced in one patient (2%) of the study group and 16 patients (32%) of the control group. No statistically significant difference was noted in incidence of premature rupture of membranes (PROM), mode of delivery, intrapartum events and perinatal outcome. No increase in neonatal morbidity was seen in association with this procedure. No patient in the study group had clinical evidence of chorioamnionitis. There was no statistically significant difference in the microbiological flora of both groups.\n Stripping of the fetal membranes is a safe and efficacious procedure for induction of labor. It decreases the incidence of induction of labor with no increase in incidence of maternal and neonatal morbidity.", "A prospective, randomized investigation was undertaken in a low-risk group of pregnant women at term (38-42 weeks' gestation) to determine if stripping the fetal membranes would safely result in earlier delivery. Ninety-nine patients entered the study; 51 underwent stripping of the membranes, and 48 controls did not. Fifty-nine percent of the patients in the stripped group delivered within one week as compared to 21% in the nonstripped group (P less than .0003). Two pregnancies in the stripped group advanced beyond 42 weeks' gestation as compared to six pregnancies in the control group (P = .12). A single gravida in the control group developed chorioamnionitis during labor. There were no other infections or other complications. Stripping the membranes was associated with earlier delivery and was not associated with any complications.", "1. To evaluate the effectiveness of sweeping of the membranes to reduce the need for a formal induction of labour; 2. to evaluate the side effects of this intervention.\n A randomised controlled clinical trial.\n Three tertiary care hospitals of the province of Quebec, Canada.\n Two hundred women for whom non-urgent induction of labour was medically indicated.\n Women were randomly allocated to sweeping of membranes, or vaginal examination for Bishop scoring only.\n 1. Cumulative incidence and relative risk of induction of labour by either oxytocin, prostaglandins or amniotomy; 2. women's discomfort and side effects attributable to sweeping of the membranes.\n Women allocated to sweeping of the membranes required formal induction of labour less frequently than women in the control group, but this difference was not statistically significant (49% vs 60%, RR 0.83, 95% CI 0.64-1.07). Pain during vaginal examination and other side effects were more frequently reported by women allocated to the sweeping group.\n The observed reduction in the need for formal induction of labour is smaller than in previous studies. Side effects and discomfort associated with sweeping of the membranes must be taken into account when counselling women who require induction of labour.", "To evaluate weekly stripping of membranes at term to determine its safety and effectiveness in reducing the incidence of prolonged and postterm pregnancies.\n One hundred forty-two pregnant women with certain gestational dates were randomly selected to receive, starting at 38 weeks, either weekly stripping of membranes (73 patients) or weekly gentle cervical examinations (69 patients).\n Women who received stripping had earlier delivery (8.2 versus 12.2 days; P < .005) and less incidence of delivery at 41 weeks or greater (three versus 13 patients; P < .01). The reduction remained consistent for favorable and unfavorable Bishop scores, and for nulliparas and multiparas. Only three subjects in the study delivered at 42 weeks or greater. No woman reported rupture of membranes after stripping.\n Stripping of membranes is a safe method to reduce the incidence of prolonged pregnancies and the length of term gestations. Larger trials on populations with a higher incidence of postterm pregnancies are needed to evaluate its efficacy in reducing the incidence of postterm pregnancies." ]

[ "16270608", "20096223", "12897561", "15584584" ]

[ "The effect of the total intravenous anesthesia compared with inhalational anesthesia on the surgical field during endoscopic sinus surgery.", "Optimizing the surgical field in pediatric functional endoscopic sinus surgery: a new evidence-based approach.", "Intravenous anesthesia provides optimal surgical conditions during microscopic and endoscopic sinus surgery.", "Total intravenous anaesthesia in endoscopic sinus-nasal surgery." ]

[ "Bleeding during endoscopic sinus surgery (ESS) may increase complications and negatively effect the surgery and its outcome. The aim of this study was to compare the surgical field in patients in whom total intravenous anesthesia (TIVA) is used as opposed to inhalation anesthesia. A prospective randomized controlled trial was performed.\n Fifty-six patients undergoing ESS were randomly assigned to receive either inhaled sevoflurane with incremental doses of fentanyl (n = 28) or TIVA via a propofol and remifentanil infusion (n = 28) for their general anesthesia. The surgical field was graded every 15 minutes using a validated scoring system.\n The two groups were matched for surgical procedure and computed tomography scores. Patients in the TIVA group were found to have a significantly lower surgical grade score than in the sevoflurane group (p < 0.001). Surgical grade score increased with time in both groups. Mean arterial pressure and pulse were found to influence the surgical field independently (p = 0.003 and p = 0.036 respectively). Mean surgical field grade scores were higher in the patients with allergic fungal sinusitis and nasal polyposis as opposed to chronic rhinosinusitis without polyps or fungus. Lund-Mackay computed tomography scores were found to correlate positively with surgical grade (Spearman rank correlation, p = 0.001).\n In patients undergoing ESS, TIVA results in a better surgical field than inhalational anesthesia.", "To conduct the first prospective randomized controlled study 1) evaluating the possibility of improving the quality of the operative field and to provide a bloodless functional endoscopic sinus surgery (FESS) in children through total intravenous anesthesia (TIVA) using remifentanil combined with propofol, and 2) testing the safety and efficacy of remifentanil in propofol-TIVA in inducing controlled hypotension in children at a target mean arterial blood pressure of 50 mm Hg.\n Randomized controlled trial.\n General hospital.\n Seventy children underwent FESS under hypotensive general anesthesia with equal randomization into two groups. Group I received TIVA with remifentanil, whereas group II had balanced anesthesia (BA) with esmolol. Heart rate, blood pressure, operative time, blood loss, and quality of the surgical conditions were recorded.\n Intraoperative blood loss in the TIVA group was less than in the BA group. The quality and dryness of the surgical field in both the visual analogue scale and the six-point scale was significantly better in the TIVA group than in the BA group. Hypotension was sustained at the target mean arterial blood pressure of 50 mm Hg in the two groups, without any significant difference.\n Improving the quality of the surgical field and providing a bloodless FESS in children is attainable with TIVA. TIVA using a combination of remifentanil and propofol is superior to BA, even with the use of additional potent hypotensive agents such as esmolol. Both techniques are safe and effective in inducing controlled hypotension in children at a target mean arterial blood pressure of 50 mm Hg.", "Controlled hypotension is used to improve surgical conditions during microscopic and endoscopic sinus surgery. New short-acting anesthetics such as propofol and remifentanil allow exact control of intraoperative blood pressure and thus might be valuable tools to improve intraoperative conditions for the otorhinolaryngological surgeon. Intravenous anesthesia was compared with traditional balanced anesthesia by subjective assessment of surgical conditions made by two experienced otorhinolaryngological surgeons.\n Prospective, randomized, patient- and observer-blinded study.\n Ninety consecutive patients were randomly assigned to receive intravenous anesthesia with propofol 5 to 8 mg.kg-1.h-1 and remifentanil 10 to 30 microg.kg-1.h-1 or with isoflurane (0.4-1.0 vol%) and repetitive doses of 0.5 to 1 mg alfentanil. An injectable vasodilator was used in both groups to keep mean arterial pressure between 60 and 70 mm Hg (8-9.3 hecto-pascal). The attending otorhinolaryngological surgeon was unaware of the type of anesthesia administered. Immediately after the operation the surgeons rated surgical conditions (bleeding from the surgical field) on a visual analogue scale (0-10 cm) and on a verbal rating scale.\n Blood pressure was not different between the two groups, but heart rate was lower in the intravenous anesthesia group (mean heart rate in the intravenous anesthesia group, 62 beats per min [95% confidence interval, 52-72]; mean heart rate in the balanced anesthesia group, 75 beats per min [95% confidence interval, 67-83]). Surgical conditions were rated to be significantly better (P <.0001) during anesthesia with propofol-remifentanil (median rating: 2.8; 25th/75th percentile: 2.0/3.4) compared with isoflurane-alfentanil (median rating: 4.9; 25th/75th percentile: 3.6/7.6).\n Intravenous anesthesia using propofol-remifentanil provides better surgical conditions compared with a traditional balanced anesthesia technique using isoflurane-alfentanil. It is hypothesized that lower cardiac output caused by decreased heart rate during deep general anesthesia is responsible for this result.", "Aim of this randomized study (64 patients) was to improve the control of bleeding during functional endoscopic sinusal surgery by means of controlled hypotension achieved through either total intravenous anaesthesia using remifentanyl and propofol (27 patients), or inhaled using isoflurane and fentanyl (37 patients). The following parameters were monitored before administration of anaesthesia (T0), then after 15 (T1), and 30 minutes (T2): systolic, diastolic, and mean arterial pressure; heart rate; concentration of tele-exhaled carbon dioxide (PetCO2) and percentage of peripheral saturation of haemoglobin (SPO2); bleeding according to the Fromme-Boezaart scale at T2. Mean arterial pressure values were maintained between 60-70 mmHg throughout surgery. At T0, systolic arterial pressure, diastolic arterial pressure and mean arterial pressure values were seen to overlap in the two groups. Both types of anaesthesia were effective in reducing the pressure values of T0-T1 and T1-T2 trends (p<0.0001). Systolic arterial pressure at T1 is lower with total intravenous anaesthesia compared to isoflurane and fentanyl (p=0.02). PetCO2 and heart rate show a decreasing trend independently of the type of anaesthesia employed. In conclusion, the hypotensive effect of total intravenous anaesthesia and of isoflurane and fentanyl is equivalent, but only total intravenous anaesthesia is effective in reducing bleeding during functional endoscopic sinusal surgery." ]

[ "8806245", "2088249", "3123043", "3073625", "2359570", "16045528", "1595797", "3533137", "3304401", "6110836", "2765430", "3685399", "7029369" ]

[ "Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid.", "Management of cyclical menorrhagia with prostaglandin synthetase inhibitor.", "Endometrial prostaglandins and menorrhagia: influence of a prostaglandin synthetase inhibitor in vivo.", "An objective evaluation of flurbiprofen and tranexamic acid in the treatment of idiopathic menorrhagia.", "The effects of mefenamic acid and norethisterone on measured menstrual blood loss.", "Randomised comparative trial of the levonorgestrel intrauterine system and mefenamic acid for the treatment of idiopathic menorrhagia: a multiple analysis using total menstrual fluid loss, menstrual blood loss and pictorial blood loss assessment charts.", "Effects of mefenamic acid on menstrual hemostasis in essential menorrhagia.", "Primary and myoma-associated menorrhagia: role of prostaglandins and effects of ibuprofen.", "Control of menorrhagia by the cyclo-oxygenase inhibitors naproxen sodium and mefenamic acid.", "Naproxen in menorrhagia.", "Comparison between mefenamic acid and danazol in the treatment of established menorrhagia.", "The effects of danazol, mefenamic acid, norethisterone and a progesterone-impregnated coil on endometrial prostaglandin concentrations in women with menorrhagia.", "Efficacy of mefenamic acid in patients with a complaint of menorrhagia." ]

[ "To compare the efficacy and acceptability of ethamsylate, mefenamic acid, and tranexamic acid for treating menorrhagia.\n Randomised controlled trial.\n A university department of obstetrics and gynaecology.\n 76 women with dysfunctional uterine bleeding.\n Treatment for five days from day 1 of menses during three consecutive menstrual periods. 27 patients were randomised to take ethamsylate 500 mg six hourly, 23 patients to take mefenamic acid 500 mg eight hourly, and 26 patients to take tranexamic acid 1 g six hourly.\n Menstrual loss measured by the alkaline haematin method in three control menstrual periods and three menstrual periods during treatment; duration of bleeding; patient's estimation of blood loss; sanitary towel usage; the occurrence of dysmenorrhoea; and unwanted events.\n Ethamsylate did not reduce mean menstrual blood loss whereas mefenamic acid reduced blood loss by 20% (mean blood loss 186 ml before treatment, 148 ml during treatment) and tranexamic acid reduced blood loss by 54% (mean blood loss 164 ml before treatment, 75 ml during treatment). Sanitary towel usage was significantly reduced in patients treated with mefenamic acid and tranexamic acid.\n Tranexamic acid given during menstruation is a safe and highly effective treatment for excessive bleeding. Patients with dysfunctional uterine bleeding should be offered medical treatment with tranexamic acid before a decision is made about surgery.", "A well controlled double blind prospective trial was undertaken to determine the efficacy of mefenamic acid in the treatment of menorrhagia. Eighty patients who had unexplained cyclical menorrhagia with secretory endometrium received mefenamic acid orally in a dose of 500 mg 8 hourly or a placebo tablet thrice daily starting from day-one of the cycle for 5 days or till cessation of menses. Mefenamic acid administration caused a statistically significant reduction in the number of days of bleeding from 9.7 +/- 3.1 days before treatment to 4.1 +/- 0.6 days after treatment. It also brought about significant reduction in the amount of bleeding in terms of number of pads used per day, that is from 15.2 +/- 3.1 before treatment to 6.5 +/- 0.02 after treatment. Eighty-six percent patients in the treatment group had control of menorrhagia with the drug compared to 20% in the control group without drugs and this difference was statistically significant. Mefenamic acid proved to be a potent and efficacious agent in the control of unexplained menorrhagia.", "Prostaglandin levels in the human endometrium were determined on day 2 of the menstrual cycle in eumenorrheic subjects and in patients with menorrhagia, dysmenorrhea, or both. Menorrhagic subjects had significantly higher levels of endometrial prostaglandins of the E and F series when compared with eumenorrheics. Prostaglandin E levels were markedly higher than prostaglandin F. In 10 menorrhagic subjects who completed a double-blind clinical study on the effectiveness of mefenamic acid in lowering menstrual blood loss, 9 exhibited statistically significant reduction in endometrial prostaglandin levels. A decrease in menstrual blood loss was also noted during mefenamic acid treatment in these patients. These findings are consistent with the concept that abnormally high uterine prostaglandin levels may be an important etiologic factor in menorrhagia and support the notion that one of the mechanisms of action of nonsteroidal anti-inflammatory agents in the treatment of this menstrual disorder is inhibition of endometrial prostaglandin production.", "The effect of flurbiprofen (100 mg x 2 for 5 days) was compared with tranexamic acid (1.5 g x 3 for 3 days, 1 g x 2 days 4 and 5) in the treatment of 15 women with idiopathic menorrhagia. The mean blood loss during two medication-free periods was 295 +/- 52 ml. A significant (p less than 0.01) reduction in menstrual blood loss was recorded during treatment with both flurbiprofen and tranexamic acid. The menstrual blood loss was significantly (p less than 0.01) lower during treatment with tranexamic acid (155 +/- 33 ml) than with flurbiprofen (223 +/- 44 ml). Various side effects were recorded by 7 of 15 women during treatment with tranexamic acid and by 4 women of 15 during treatment with flurbiprofen. Many women with menorrhagia suffer simultaneously from dysmenorrhea. Thus although tranexamic acid was generally more effective in reducing menstrual blood loss, flurbiprofen provides an important therapeutic alternative to antifibrinolytic agents, especially in patients with concomitant dysmenorrhea.", "Although there are numerous medical treatments for menorrhagia, in many instances neither the precise diagnosis nor the response to therapy have been assessed objectively. Menorrhagia (menstrual blood loss more than 80 mL per cycle) was diagnosed objectively in 32 (44%) of 72 women with a subjective complaint of heavy menses. All of the 32 women had ovulatory cycles. After random allocation to treatment with either mefenamic acid (500 mg three times daily during menses, N = 17) or norethisterone (5 mg twice daily on days 19-26 of the cycle, N = 15) for two additional cycles, the median menstrual blood loss was reduced from 123 mL (range 86-237) to 81 mL (22-193) (P less than .001) and from 109 mL (81-236) to 92 mL (43-189) (P less than .002) with mefenamic acid and norethisterone, respectively. Apart from a decrease in the median number of days of bleeding, from 7 (5-8) to 5 (3-8) in those women treated with mefenamic acid, no other differences were seen between the groups. We conclude that mefenamic acid and norethisterone were similarly effective in reducing the degree of menstrual blood loss in women with proved menorrhagia, but that 52 and 67% of the women, respectively, remained menorrhagic after 2 months of treatment.", "To compare the efficacy and tolerability of the levonorgestrel intrauterine system (LNG IUS) with mefenamic acid in the management of objective idiopathic menorrhagia.\n Phase III, Single centre, open, randomised, comparative, parallel group study.\n District General Hospital in the United Kingdom.\n Fifty-one women with objective menorrhagia.\n Twenty-five women randomised to receive the LNG IUS and 26 to oral mefenamic acid for six cycles.\n Change from baseline in menstrual blood loss (MBL), total menstrual fluid loss (TMFL) and pictorial blood loss assessment chart (PBAC) score at the third and sixth cycle of treatment.\n After six cycles the median menstrual blood loss was 5 mL in the LNG IUS group and 100 mL in the mefenamic acid group (P < 0.001). Median TMFL was 27 mL in the LNG IUS group and 157 mL in the mefenamic acid group (P < 0.001). Median PBAC score was 25 in the LNG IUS group and 159 in the mefenamic acid group. Changes in menstrual blood loss correlated strongly to changes in TMFL (r= 0.88) but PBAC correlated less well to blood loss and total fluid loss (r= 0.53 and r= 0.58).\n Both the LNG IUS and mefenamic acid significantly decreased menstrual blood loss, TMFL and PBAC scores. The LNG IUS produced greater reductions in all parameters than mefenamic acid. Comparison of the different measurements suggests that TMFL assessment may be an easier and a more relevant measure of symptom severity than menstrual blood loss.", "Prostaglandin synthesis inhibitors decrease menstrual blood loss by 30% to 50% in patients with essential menorrhagia. To obtain insight into their mechanism of action, we measured menstrual blood loss in menorrhagic women, who were receiving mefenamic acid (500 mg, three times daily) (n = 6) or placebo (n = 5) in a double-blind way. In addition we studied the morphology of early menstrual hemostasis. The subjects' uteri were extirpated in the first 24 hours of menstruation, and light and electron microscopy were used to perform morphologic and morphometric studies. In the group treated with mefenamic acid mean menstrual blood loss was decreased by 40%. In uteri of the women treated with mefenamic acid hemostatic plugs were further transformed, and fewer vessels without a plug were observed than in uteri of the group receiving placebo. These data suggest that mefenamic acid may act through an improvement of platelet aggregation and degranulation and through increased vasoconstriction.", "The release of 6-keto-prostaglandin F1 alpha(6-keto-PGF1 alpha), a metabolite of prostacyclin (PGI2) and thromboxane B2 (TxB2), a metabolite of thromboxane A2 (TxA2), was estimated in endometrial biopsies taken from 12 menorrhagic and 12 healthy women during the luteal phase of the cycle. The releases of 6-keto-PGF1 alpha and TxB2 were normal, but the ratio TxB2/6-keto-PGF1 alpha was inversely related to menstrual blood loss in women with measured menstrual blood loss exceeding 70 ml. In the second part of the study, 24 women with excessive menstrual bleeding (13 with primary menorrhagia, 10 with uterine fibromyomas, one with haemostatic factor VIII deficiency) were treated at random with ibuprofen (600 mg/day and 1200 mg/day) and with a placebo. Ibuprofen 1200 mg/day reduced (P less than 0.01) median blood loss from 146 ml (range 71-374 ml) to 110 ml (30-288 ml) in primary menorrhagia but had no effect on blood loss in women with uterine fibroids and factor VIII deficiency. Blood loss was normal in six women and was not affected by ibuprofen. Thus, our data suggest that there is a PGI2 dominance in the endometrium of patients with menorrhagia. In addition, primary, but neither fibromyoma nor coagulation defect-associated menorrhagia, can be treated by ibuprofen.", "Thirty-five patients with menorrhagia were treated in a double-blind crossover study with naproxen sodium and mefenamic acid after measurement of their blood loss during control menstrual cycles. Treatment with these compounds reduced the excessive bleeding by an average of 46 and 47% respectively. Drugs in the prostaglandin synthetase inhibitor group are considered to have an important place in the treatment of menorrhagia.", "nan", "Forty women with established menorrhagia were treated with either mefenamic acid (500 mg thrice daily for 3-5 days in two cycles) or danazol (100 mg twice daily for 60 days) in an open parallel group randomized study. Mefenamic acid reduced mean menstrual blood loss from 160 ml to 127 ml (20%, P less than 0.01). Danazol reduced mean menstrual loss from 163 ml to 65 ml (60%, P less than 0.001). The percentage reduction in menstrual blood loss was significantly greater in the danazol group than in the mefenamic acid group, but the adverse side-effects occurred significantly more often in the danazol group (75%) than in the mefenamic acid group (30%, P less than 0.005). Overall, approximately half the women in each group were prepared to continue with the treatment they received to reduce their menstrual bleeding.", "The effects of four medical treatments have been assessed on menstrual blood loss (MBL) and endometrial prostaglandin (PG) concentrations in 30 women with objectively confirmed menorrhagia. Patients were randomly treated with danazol, 200 mg daily (n = 6), mefenamic acid, 500 mg three times daily during menses (n = 8), norethisterone, 5 mg twice daily from day 15-25 of the cycle (n = 8) or a progesterone-impregnated coil releasing 65 micrograms progesterone daily (n = 8). Endometrial biopsies were obtained in the mid-luteal phase before and after treatment in 23 cases, and assayed for PG content using radioimmunoassay. Treatment with norethisterone had no effect on either MBL or the concentration of PGs in the endometrium. MBL was significantly reduced after treatment with mefenamic acid (P = 0.05, n = 6) and the progesterone coil (P less than 0.05, n = 6), and was reduced in each of 4 cases treated with danazol in whom endometrial biopsies were available. Although there was no consistent change in endometrial PG concentrations in either the mefenamic acid or danazol groups, the lower MBL after insertion of the progesterone coil was associated with a reduced endometrial content of PGE, PGF2 alpha and \"total\" PG (6oxo PGF1 alpha + PGE + PGF2 alpha)-P = 0.05. Whereas the cyclooxygenase inhibitor mefenamic acid is likely to exert its effect on endometrial PGs at the time of menstruation itself, the continuous administration of progesterone throughout the menstrual cycle could result in both an impairment in estrogen receptor generation leading to reduced estrogen-mediated cyclooxygenase activity, and an increase in endometrial PG metabolism.", "Sixty-nine patients with a convincing history of menorrhagia completed a 4-cycle double-blind randomized placebo-controlled crossover trial of mefenamic acid taken during menstruation. Only 30 of these patients demonstrated objective menorrhagia with a measured menstrual loss greater than 80 ml during the placebo cycles, but the remainder reported passing clots and/or using 2 pads at a time. Fourteen of these women (20%) had a loss of less than 35 ml while taking placebos. This raises serious questions about the establishment of menorrhagia based on history alone. Overall, there was a mean reduction of 28.1% in menstrual blood loss between placebo and mefenamic acid cycles (P less than .001). The greatest reduction recorded was 80%, and most of the large percentage reductions were seen in patients with high loss during placebo cycles. Significant reductions in blood loss (P less than .001) were seen in patients with ovulatory dysfunctional uterine bleeding and menorrhagia that developed after tubal interruption. There was also an indication based on small sample sizes that mefenamic acid reduced blood loss in women with anovulatory dysfunctional uterine bleeding, fibroids, intrauterine devices, and von Willebrand disease. No reduction was seen during the mefenamic acid cycle in the group with a loss of less than 35 ml during the placebo cycle. There was a significant shortening of duration of bleeding (P less than .003). Fifteen patients (21.7%) experienced no objective reduction in blood loss." ]

[ "4761382", "5558855" ]

[ "The effects of abdominal decompression on pregnancy complicated by the small-for-dates fetus.", "Clinical and endocrinological aspects of dysmaturity and the use of intermittent abdominal decompression in pregnancy." ]

[ "nan", "nan" ]

[ "4596108", "11978253", "5330074", "4097904", "329949", "4932022" ]

[ "The value of antibiotics in minor respiratory illness in children. A controlled trial.", "Does amoxicillin improve outcomes in patients with purulent rhinorrhea? A pragmatic randomized double-blind controlled trial in family practice.", "Medical management of purulent rhinitis. A double-blind comparison of vasoconstrictor agent alone with a combination of vasoconstrictor and antimicrobial drugs.", "Double-blind trial of early demethylchlortetracycline in minor respiratory illness in general practice.", "Amoxycillin and co-trimoxazole in presumed viral respiratory infections of childhood: placebo-controlled trial.", "Evaluation of orally administered antibiotics for treatment of upper respiratory infections in Thai children." ]

[ "nan", "To compare the efficacy of amoxicillin vs placebo in patients with an acute upper respiratory tract infection and purulent rhinorrhea.\n Double-blind randomized placebo-controlled trial.\n The 416 patients included from 69 family practices were 12 years or older, presenting with acute upper respiratory complaints, and having a history of purulent rhinorrhea and no signs of complications of sinusitis.\n Therapy success (disappearance of symptoms that most greatly affected the patient's health) at day 10 and duration of general illness, pain, and purulent rhinorrhea.\n Therapy was successful in 35% of patients with amoxicillin and in 29% of patients with placebo (relative risk [RR] 1.14, 95% confidence interval [CI], 0.92-1.42). There was no effect on duration of general illness or pain. Duration of purulent rhinorrhea was shortened by amoxicillin (9 days vs 14 for clearing of purulent rhinorrhea in 75% of patients; P =.007). Diarrhea was more frequent with amoxicillin (29% vs 19%, RR 1.28, 95% CI, 1.05-1.57). No complications were reported. One patient (0.5%) receiving amoxicillin and 7 (3.4%) receiving placebo discontinued trial therapy because of exacerbation of symptoms (RR 0.25, 95% CI 0.04-1.56, P =.07). All 8 patients recovered with antibiotic therapy.\n Amoxicillin has a beneficial effect on purulent rhinorrhea caused by an acute infection of the nose or sinuses but not on general recovery. The practical implication is that all such patients, whatever the suspected diagnosis, can be safely treated with symptomatic therapy and instructed to return if symptoms worsen.", "nan", "nan", "A double-blind randomized controlled trial of amoxycillin, co-trimoxazole, and placebo was conducted on 197 children presenting with presumed viral respiratory infections. Routine throat swabs were taken to exclude streptococcal diseases. The three disease categories studied--nasopharyngitis, pharyngotonsillitis, and bronchitis (including laryngotracheobronchitis)--showed a generally similar pattern of resolution irrespective of treatment. Nevertheless, seven out of 66 children receiving placebo were withdrawn from the trial with unremitting symptoms or complications thought to require antimicrobial treatment. Only two of 56 children receiving amoxycillin and none of 75 receiving co-trimoxazole were withdrawn. Three other children receiving amoxycillin and three receiving placebo were seen during the trial but further treatment was not thought to be necessary. Thus the return consultation rate in children receiving placebo therapy was 15% compared with 4% for those receiving antimicrobial treatment. Antimicrobial treatment was associated with less nasal discharge on the eighth day of treatment. Placebo treatment allowed an earlier return to normal activity. There was a high incidence of possible side effects on all regimens including placebo. It is concluded that the benefits of antimicrobial treatment in presumed viral respiratory infections are marginal, and they should not be routinely prescribed for these conditions.", "nan" ]

[ "7758213", "7658286", "12499335", "11120904" ]

[ "Effect of double-blind cross-over selenium supplementation on lipid peroxidation markers in cystic fibrosis patients.", "Single- and multiple-dose-response relationships of beta-carotene in cystic fibrosis.", "Improved antioxidant and fatty acid status of patients with cystic fibrosis after antioxidant supplementation is linked to improved lung function.", "Effects of beta-carotene supplementation for six months on clinical and laboratory parameters in patients with cystic fibrosis." ]

[ "Lipid peroxidation was assessed in 27 cystic fibrosis children during a double-blind selenium supplementation study (2.8 micrograms of sodium selenite per kg per day) with a placebo control and inversion of treatment periods. Simultaneously, 17 healthy children living in the same area were also investigated as control subjects. Before any treatment whatsoever and despite a selenium status close to those of control subjects, cystic fibrosis patients showed significant increase in plasma lipid peroxidation markers. Thiobarbituric acid reactants (TBARs) were normalized after the first treatment period of 5 months in both cystic fibrosis groups receiving either selenium supplementation or placebo. In this latter group, TBARs were reduced despite a significant decrease in plasma selenium concentrations as compared with the control group. Organic hydroperoxide concentrations were also simultaneously normalized in both cystic fibrosis groups at the end of the second treatment period. These results showed that improvement of lipid peroxidation markers was not related to the selenium supplementation. Nevertheless, oxidative stress sustained by cystic fibrosis children must be taken into account so that it does not aggravate the prognosis of the disease.", "Concentrations of carotenoids are low in patients with cystic fibrosis (CF) and are associated with essential fatty acid deficiency and increased markers of inflammation. We conducted single- and multiple-dose studies of beta-carotene supplementation in patients with CF. Dose-proportional increases in beta-carotene concentrations were found, although clearance was independent of dose. Large doses of beta-carotene were necessary to achieve normal plasma levels.", "Oxidative stress, as measured by 8-iso-prostaglandin F(2)(alpha) (8-iso-PGF(2)(alpha)), and depleted antioxidant defenses were shown in stable cystic fibrosis (CF) patients. The plasma fatty acid status of CF patients was linked to oxidative stress after respiratory exacerbations.\n We examined changes in plasma 8-iso-PGF(2)(alpha), antioxidant defenses, plasma fatty acid status, and clinical markers resulting from short-term antioxidant supplementation.\n Forty-six CF patients were randomly assigned to either group A [low dose of supplement (10 mg vitamin E and 500 micro g vitamin A)] or group B [high dose of supplement (200 mg vitamin E, 300 mg vitamin C, 25 mg beta-carotene, 90 micro g Se, and 500 micro g vitamin A)]. Plasma concentrations of 8-iso-PGF(2)(alpha), vitamins E and C, beta-carotene, zinc, selenium, and copper; plasma fatty acid composition; erythrocyte glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities; lung function; and dietary intake were measured before and after 8 wk of supplementation.\n Antioxidant defenses in group B improved, whereas those in group A did not: in groups B and A, the mean (+/- SEM) changes (Delta) in vitamin E were 10.6 +/- 1.5 and -1.9 +/- 0.9 micro mol/L, respectively (P < 0.001), (Delta)beta-carotene were 0.1 +/- 0.04 and -0.01 +/- 0.02 micro mol/L, respectively (P = 0.007), (Delta)selenium were 0.51 +/- 0.10 and -0.09 +/- 0.04 micro mol/L, respectively (P < 0.001), and (Delta)glutathione peroxidase activity were 1.3 +/- 0.3 and -0.3 +/- 0.6 U/g hemoglobin, respectively (P = 0.016). There were no significant differences between the groups in Delta8-iso-PGF(2)(alpha), (Delta)vitamin C, (Delta)fatty acid composition, (Delta)superoxide dismutase activity, (Delta)lung function, or (Delta)white cell count. Within group B, (Delta)beta-carotene correlated with (Delta)percentage of forced vital capacity (r = 0.586, P = 0.005), (Delta)selenium correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.440, P = 0.046), and (Delta)plasma fatty acid concentrations correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.583, P = 0.006) and Delta8-iso-PGF(2)(alpha) (r = 0.538, P = 0.010).\n Whereas increased beta-carotene, selenium, and fatty acid concentrations are linked to improved lung function, increased plasma fatty acid concentrations are linked to oxidative stress. If oxidative stress is deemed to be important to the clinical outcome of CF patients, means of reducing oxidative stress while maintaining a high-fat, high-energy diet must be investigated.", "Patients with cystic fibrosis (CF) have significantly decreased plasma concentrations of nutrient antioxidant vitamins, especially of beta-carotene, which is thought to result from fat malabsorption and chronic pulmonary inflammation. The aim of this double blind, placebo controlled study was to investigate the effect of oral beta-carotene supplementation for six months on clinical parameters.\n Twenty four patients with CF were randomised to receive beta-carotene 1 mg/kg/day (maximum 50 mg/day) for three months (high dose supplementation) and 10 mg/day for a further three months (low dose supplementation) or placebo. At monthly follow up visits the plasma beta-carotene concentration, total antioxidant capacity, malondialdehyde (MDA) as a marker of lipid peroxidation, and clinical parameters (Shwachmann-Kulczycki score, body mass index (BMI), height, and lung function (FEV(1))) were assessed. The number of pulmonary exacerbations requiring antibiotic treatment (in days) three months before and during the study were evaluated.\n The plasma concentration of beta-carotene increased significantly to the normal range during the three months of high dose supplementation (baseline 0.08 (0.04) micromol/l to 0.56 (0.38) micromol/l; p<0.001) but decreased to 0.32 (0.19) micromol/l in the period of low dose supplementation. Initially raised plasma levels of MDA fell to normal levels and the total antioxidant capacity showed a non-significant trend towards improvement during high dose supplementation. Antibiotic treatment decreased significantly in the supplementation group from 14.5 (14.9) days/patient during the three months before the study to 9.8 (10.3) days/patient during high dose supplementation (p=0.0368) and to 10.5 (9.9) days/patient during low dose supplementation, but increased in the placebo group. The Shwachmann-Kulczycki score, lung function, and BMI did not show any changes in either of the treatment groups. No adverse events were observed during the study period.\n Oral beta-carotene supplementation in a dose of 1 mg/kg/day only was effective in normalising the plasma concentration of beta-carotene and resulted in a decrease in pulmonary exacerbations. These data suggest that patients with CF may benefit clinically from supplementation with beta-carotene and further studies are warranted." ]

[ "2505689", "7014814", "1473544", "6768286" ]

[ "Randomised controlled trial of two methods of weaning from high frequency positive pressure ventilation.", "Prospective clinical comparison of two methods for mechanical ventilation of neonates: rapid rate and short inspiratory time versus slow rate and long inspiratory time.", "Decreased incidence of extra-alveolar air leakage or death prior to air leakage in high versus low rate positive pressure ventilation: results of a randomised seven-centre trial in preterm infants.", "Hyaline membrane disease. A controlled study of inspiratory to expiratory ratio in its management by ventilator." ]

[ "Forty preterm infants suffering from respiratory distress syndrome were entered into a randomised controlled trial to assess the importance of the length of inspiratory time during weaning from high frequency positive pressure ventilation (HFPPV). Two weaning regimes were compared: in one (group A) inspiratory time was limited to 0.5 seconds throughout weaning, in the other (group B) ventilator rate was reduced by increasing both inspiratory and expiratory time (inspiration:expiration ratio constant) until inspiratory time reached 1.0 seconds. At ventilator rates of 20 and 40 breaths/minute an acute comparison was made in all 40 infants of the two inspiratory times; despite the lower mean airway pressure associated with the shorter inspiratory time blood gases were maintained. There was no difference in the incidence of pneumothoraces or need for reventilation between the two regimens but infants in group A had a shorter duration of weaning. We conclude limitation of inspiratory time to 0.5 seconds during weaning from HFPPV is advantageous to preterm infants with respiratory distress syndrome.", "A prospective comparison was made of the clinical courses of two groups of neonates ventilated according to different protocols: one group at rates of 20 to 40/minute with a one-second IT, and the other at a rate of 60/minute and 0.5 second IT. Other ventilator settings were adjusted within protocol limits to maintain desired blood gas values. Mean starting and highest PIP were lower in the rapid rate group. The results showed no difference in mortality, failure to remain within protocol limits, time requiring respiratory treatment or FiO2 more than 0.6, and incidence of PDA or chronic lung disease. There was a difference (P = 0.011) in number of infants developing pneumothoraces (14% in the rapid group vs 35% in the slow group). Rapid rate ventilation can be used to decrease the incidence of pneumothorax, reserving long IT and higher PIP for infants who cannot be oxygenated or ventilated without them.", "Two different ventilation techniques were compared in a seven-centre, randomised trial with 181 preterm infants up to and including 32 completed weeks gestational age, who needed mechanical ventilation because of lung disease of any type. Technique A used a constant rate (60 cycles/min), inspiratory time (IT) (0.33s) and inspiratory: expiratory ratio (I:E) (1:2). The tidal and minute volume was only changed by varying peak inspiratory pressure until weaning via continuous positive airway pressure. Technique B used a lower rate (30 cycles/min) with longer IT (1.0 s). The I:E ratio could be changed from 1:1 to 2:1 in case of hypoxaemia. Chest X-rays taken at fixed intervals were evaluated by a paediatric radiologist and a neonatologist unaware of the type of ventilation used in the patients. A reduction of at least 20% in extra-alveolar air leakage (EAL) or death prior to EAL was supposed in infants ventilated by method A. A sequential design was used to test this hypothesis. The null hypothesis was rejected (P = 0.05) when the 22nd untied pair was completed. The largest reduction in EAL (-55%) was observed in the subgroup 31-32 weeks of gestation and none in the most immature group (< 28 weeks). We conclude that in preterm infants requiring mechanical ventilation for any reason of lung insufficiency, ventilation at 60 cycles/min and short IT (0.33 s) significantly reduces EAL or prior death compared with 30 cycles/min and a longer IT of 1 s. We speculate that a further increase in rate and reduction of IT would also lower the risk of barotrauma in the most immature and susceptible infants.", "Sixty-nine neonates with severe hyaline membrane disease (HMD) were mechanically ventilated using either a 1:2 or a 2:1 inspiratory to expiratory (I/E) ratio. Survivors in the 2:1 group required a lower fraction of oxygen in the inspired air (FiO2) and lower end-expiratory pressure to achieve satisfactory oxygenation. During the first week of life, time of exposure to FiO2 greater than 0.60 while being mechanically ventilated was 29.7 +/- 7.5 hours for the 1:2 group and 6.6 +/- 2,7 hours for the 2:1 group, while time of exposure to end-expiratory pressure greater than 3 cm H2O was 49.4 +/- 7.9 hours for the 1:2 group and 13.4 +/- 7.4 hours for the 2:1 group. Mortality and the incidence of air leak, patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, and pulmonary hemorrhage were not different for the two groups. Using an increased I/E ratio during the acute phase of HMD improved oxygenation but did not alter morbidity or mortality." ]

[ "9085210", "3303936" ]

[ "Betamimetics in fetal distress: randomised controlled trial.", "A study on intrauterine fetal resuscitation with terbutaline." ]

[ "The objective of the study was to investigate if a single dose of Hexoprenaline administered to patients diagnosed as having fetal distress improves neonatal outcome and whether there are any side effects and complications related to hexoprenaline injection. Patients with fetal distress diagnosed by electronic fetal heart rate monitoring with a gestational age of 35 weeks or more in active labor were eligible. Once the decision to deliver the patient by Cesarean section was made, patients were approached and randomised by sealed opaque envelopes to hexoprenaline or control groups. Ten micrograms of hexoprenaline were administered intravenously to study patients. Main outcomes were cord blood gas values, Apgar scores, the need for resuscitation and admission to intensive care. There were no statistically significant differences in the main outcome measures between the two groups. Fewer babies in the hexoprenaline group had a pH of < 7.2 and a base excess of < -10, but this was not statistically significant. The fetal heart rate pattern was improved in significantly more patients after hexoprenaline administration than controls. In conclusion, despite the statistically significant improvement in fetal heart rate tracings, Apgar scores and blood gas values showed only a trend towards improvement in the hexoprenaline group.", "A randomized study on the effect of terbutaline on fetal distress was carried out in 20 patients who showed evidence of ominous fetal heart rate patterns and fetal scalp blood pH values of less than 7.25. Of those, 11 received terbutaline (study group) and nine did not (control group). There was a significant improvement in the acid-base status of the fetus in the study group compared with those in the control group (p less than 0.01). No significant maternal or fetal morbidity occurred in the study group. Apgar scores at 1 minute were 7 or greater in 10 of the 11 study subjects whereas only four of the nine control subjects had a score of 7 or greater. These results suggest that terbutaline may become a useful agent in the treatment of intrauterine fetal distress." ]

[ "8444226", "1738219" ]

[ "Randomised controlled trial of albumin infusion in ill preterm infants.", "Concurrent administration of albumin with total parenteral nutrition in sick newborn infants." ]

[ "We assessed the effect of albumin infusion on weight loss and ventilation requirement in sick premature infants. Thirty infants, median gestational age 29 weeks, were entered into a randomised controlled trial, at a median of 2 days of age. The infants, all with an albumin level < or = 30 g/l, received either 5 ml/kg of 20% albumin or 5 ml/kg of their maintenance fluids (placebo), both given as part of the total daily fluid requirement. The response to the infusion was assessed by comparing two periods; 12 h immediately prior to the infusion and 12-24 h after the infusion. Albumin infusion was associated with a significant increase in albumin level and a significant reduction in weight, but in the placebo group there was a significant increase in weight. There were, however, no significant changes in the peak inspiratory pressure in response to either infusion. There was only a modest reduction (< 15%) in the inspired oxygen concentration, which occurred in both groups, but reached statistical significance only following the albumin infusion. We conclude that our results suggest that albumin infusion in \"hypoalbuminaemic\" sick preterm infants is unlikely to alter their respiratory status.", "The effects of concurrent administration of albumin with total parenteral nutrition were studied in 12 premature newborns (birth weight 1.26 +/- 0.1 kg [mean +/- SEM] and gestational age 30 +/- 0.8 weeks [mean +/- SEM]) compared with a control group of 12 premature newborns (birth weight 1.17 +/- 0.2 kg and gestational age 29 +/- 0.1 weeks) who received total parenteral nutrition. All newborns had a plasma albumin level below 3 g/dL and were in cardiorespiratory distress requiring assisted ventilation. Albumin supplementation of total parenteral nutrition resulted in a sustained increase in serum albumin concentration as well as increased mean arterial blood pressures in the study group. Slow albumin infusion had no observed effect on the severity of respiratory distress. Study group infants regained birth weight earlier than control group infants. These data suggest that the concurrent administration of albumin may be clinically beneficial in critically ill newborn infants." ]

[ "7427048" ]

[ "A physiological study of elastic compression stockings in venous disorders of the leg." ]

[ "The physiological effects of elastic compression stockings on venous disorders of the leg have been studied in three groups of 10 patients. These patients were divided by examination and ascending venography into those with: (a) a normal venous system in the leg, (b) superficial varicose veins and (c) a post-phlebitic limb. In a randomized cross-over trial each groups wore Eesiness NHS two-way stretch or Sigvaris medium compression below-knee stockings for three weeks. In the post-phlebitic limb group a further comparison was made with Sigvaris strong compression below-knee stockings after a 6-week rest period. The effects were objectively compared using foot volumetry and sodium (24Na) subcutaneous tissue clearance. The physiological benefits of Sigvaris medium and strong compression stockings were comprehensively demonstrated by both methods of assessment in patients with the post-phlebitic limb. Benefit from Sigvaris medium compression stockings was also demonstrated in the patients with varicose veins. In the group with normal veins there were negligible physiological benefits from compression stockings. Eesiness stockings failed to produce a significant physiological effect in each group." ]

[ "9019175", "8001208", "8949806", "8738686", "7902034", "9849280", "9842809", "16243994", "16492856", "9483596", "1616158", "10553857", "11407293", "8872689", "10386278", "10536557", "9195356", "9389261", "1389845", "11090730", "9257203", "12699517", "11737185", "8610912", "9926179", "8832448", "16517330", "7772357" ]

[ "[Intubation requirements after rocuronium and succinylcholine].", "Different priming techniques, including mivacurium, accelerate the onset of rocuronium.", "Influence of induction technique on intubating conditions after rocuronium in adults: comparison with rapid-sequence induction using thiopentone and suxamethonium.", "Comparison of intubating conditions after rocuronium and suxamethonium following \"rapid-sequence induction\" with thiopentone in elective cases.", "Comparison of rocuronium, succinylcholine, and vecuronium for rapid-sequence induction of anesthesia in adult patients.", "Comparison of rocuronium and suxamethonium for use during rapid sequence induction of anaesthesia.", "Rocuronium versus succinylcholine: are they equally effective during rapid-sequence induction of anesthesia?", "Rocuronium versus succinylcholine for rapid sequence induction of anesthesia and endotracheal intubation: a prospective, randomized trial in emergent cases.", "Rocuronium is not associated with more vocal cord injuries than succinylcholine after rapid-sequence induction: a randomized, prospective, controlled trial.", "Onset of neuromuscular blockade and intubating conditions one minute after the administration of rocuronium in children.", "Evaluation of the endotracheal intubating conditions of rocuronium (ORG 9426) and succinylcholine in outpatient surgery.", "Visual estimation of onset time at the orbicularis oculi after five muscle relaxants: application to clinical monitoring of tracheal intubation.", "Effectiveness and safety of rocuronium-hypnotic sequence for rapid-sequence induction.", "A mixture of mivacurium and rocuronium is comparable in clinical onset to succinylcholine.", "Intraocular pressure changes during rapid sequence induction and intubation: a comparison of rocuronium, atracurium, and succinylcholine.", "Effect of rocuronium compared with succinylcholine on intraocular pressure during rapid sequence induction of anaesthesia.", "Rocuronium versus succinylcholine for rapid-sequence induction using a variation of the timing principle.", "Comparison of suxamethonium and different combinations of rocuronium and mivacurium for rapid tracheal intubation in children.", "Comparison of intubating conditions after administration of Org 9246 (rocuronium) and suxamethonium.", "Rocuronium versus succinylcholine-atracurium for tracheal intubation and maintenance relaxation during propofol anesthesia.", "Double-blind comparison of two doses of rocuronium and succinylcholine for rapid-sequence intubation.", "Rocuronium combined with i.v. lidocaine for rapid tracheal intubation.", "The effect of rocuronium on intraocular pressure: a comparison with succinylcholine.", "Comparison of rocuronium and mivacurium to succinylcholine during outpatient laparoscopic surgery.", "A large simple randomized trial of rocuronium versus succinylcholine in rapid-sequence induction of anaesthesia along with propofol.", "Rocuronium priming of atracurium-induced neuromuscular blockade: the use of short priming intervals.", "Is there an ideal approach for rapid-sequence induction in hypertensive patients?", "Pharmacodynamics of rocuronium with and without prior administration of succinylcholine." ]

[ "Rocuronium is a new non-depolarising steroidal muscle relaxant with a short onset time. The present study was undertaken to compare intubating conditions as well as onset and clinical duration of a single dose of 0.6 mg/kg (2 x ED95) with a single dose of 1 mg/kg suxamethonium (3 x ED95).\n After obtaining informed consent and approval of the Ethics Committee, 40 adult patients (ASA I-III) participated in this study. After premedication with oxazepam, anaesthesia was induced with fentanyl and propofol and maintained with propofol, N2O and supplements of fentanyl as needed. Muscular relaxation was assessed by EMG recording of adductor pollicis muscle after supramaximal single twitch stimulation of the ulnar nerve every 10 s. Patients were allocated randomly to receive either rocuronium 0.6 mg/kg or suxamethonium 1 mg/kg. The following parameters were measured: intubating conditions 60 s after injection, onset time and clinical duration of neuromuscular block, % block at intubation, heart rate, blood pressure and arterial oxygen saturation.\n (mean +/- SD). Intubating conditions after rocuronium and suxamethonium were found to be clinically acceptable (excellent or good) in 90% of patients, though there was only a partial blockade of the adductor pollicis muscle with rocuronium (71 +/- 23%) compared to suxamethonium (95 +/- 14%) (p < 0.05). The onset time and clinical duration of relaxation was shorter after suxamethonium (p < 0.05) and occurred at 0.8 +/- 0.2, 7 +/- 2.1 and 3.2 +/- 1.3, 29 +/- 11 min after suxamethonium and rocuronium respectively.\n At a dosage of 0.6 mg/kg, rocuronium has an onset time of about 3 min and a clinical duration of relaxation of nearly half an hour. These data are supported by various studies, while others show shorter times, probably due to different monitoring techniques. In spite of the pharmacodynamic differences between suxamethonium and rocuronium, the intubating conditions after administration of both compounds are comparable and develop at the same rate.", "Different priming sequences of equipotent doses of rocuronium and mivacurium on the onset of maximum neuromuscular block and intubating conditions were compared with those obtained after succinylcholine. During thiopentone-fentanylnitrous oxide anaesthesia, 70 patients were randomly assigned into seven groups. Group I received mivacurium 0.15 mg.kg-1 as a single bolus dose. Group II received a priming dose of mivacurium 0.015 mg.kg-1 followed three minutes later by mivacurium 0.135 mg.kg-1. Group III received rocuronium 0.6 mg.kg-1 as a single bolus dose, and Group IV received an initial dose of rocuronium 0.06 mg.kg-1 followed by rocuronium 0.54 mg.kg-1. Group V received a priming dose of mivacurium 0.015 mg.kg-1 followed by rocuronium 0.54 mg.kg-1. Group VI received an initial dose of rocuronium 0.06 mg.kg-1 followed by mivacurium 0.135 mg.kg-1. Group VII received succinylcholine 1.0 mg.kg-1. Groups I, III, and VII received a placebo injection before the administration of the neuromuscular blocking drug. Additional thiopentone 2 mg.kg-1 iv was given 30 sec before intubation. Onset times (mean (95% confidence interval)) after priming a rocuronium block with either rocuronium (73 (57-90) sec) or mivacurium (58 (47-69) sec) were similar to those after succinylcholine (54 (40-68) sec), and were shorter (P < 0.01) than that observed in other groups. Intubating conditions were not different between the groups. The duration of neuromuscular block was shortest with succinylcholine. It is concluded that priming a rocuronium block with either mivacurium or rocuronium resulted in a neuromuscular block comparable to that of succinylcholine in both the onset of action and intubating conditions.", "We have assessed the effect of anaesthetic technique on intubating conditions after rocuronium 0.6 mg kg-1 in four groups (n = 25 each) of unpremedicated patients in whom anaesthesia was induced with either thiopentone 5 mg kg-1 or propofol 2.5 mg kg-1 alone, or supplemented with alfentanil 20 micrograms kg-1. Fifty control patients were anaesthetized with thiopentone followed by suxamethonium. Laryngoscopy was commenced at 45 s. Overall intubating conditions after rocuronium were similar to those after suxamethonium (good and excellent > or = 96%) only when alfentanil was part of the induction regimen. However, intubation time was similar in all five groups and averaged 55 (SD 3.2) s, and the tube could be passed through open vocal cords within 70 s. After rocuronium the response of the diaphragm to intubation was more pronounced in the two groups of patients not receiving alfentanil (P < 0.0001) and in patients anaesthetized using propofol with alfentanil (P < 0.01) than in the control group. Opioids (in doses equivalent to alfentanil 20 micrograms kg-1) constitute an integral part of an induction regimen containing rocuronium 0.6 mg kg-1, regardless of whether or not thiopentone or propofol is used, in order to achieve overall intubating conditions similar to those after suxamethonium.", "Rocuronium (Org 9426) was shown to have the fastest onset of action of all currently available non-depolarizing neuromuscular blocking drugs and to provide intubating conditions similar to those of suxamethonium 60 to 90 s after administration. We compared the intubating conditions after rocuronium and suxamethonium following rapid-sequence induction of anaesthesia.\n Fifty unpremedicated patients of ASA physical status I or II, scheduled for elective surgery were studied. Anaesthesia was induced with thiopentone 6 mg kg-1 followed randomly by suxamethonium 1 mg kg-1 or rocuronium 0.6 mg kg-1 and, 45 s later, intubation was commenced. Muscle fasciculations, intubating conditions and intubation time, haemodynamic variables and oxygenation were assessed.\n Intubation time did not differ between suxamethonium (9.8 +/- 2.2 s) (mean +/- SD) and rocuronium (10.5 +/- 2.9 s), respectively. Intubating conditions were clinically acceptable (good or excellent) in all patients given suxamethonium and in 96% of the patients given rocuronium. However, the condition of the vocal cords was better (P < 0.05) and diaphragmatic response to intubation was less pronounced with suxamethonium (P < 0.05). Changes in heart rate and arterial blood pressure were similar in both groups.\n The authors conclude that rocuronium is a suitable alternative to suxamethonium for rapid tracheal intubation even under unsupplemented thiopentone anaesthesia, at least in elective, otherwise healthy patients. Its use for rapid-sequence induction under emergency conditions, however, needs further investigation.", "Succinylcholine has been the agent of choice when clinical conditions require emergency airway protection during a rapid-sequence induction of anesthesia. Rocuronium, a new nondepolarizing muscle relaxant with a brief onset of action, but devoid of the adverse reactions associated with succinylcholine, may be an alternative to succinylcholine. To test this hypothesis, the authors compared rocuronium with succinylcholine and vecuronium for rapid-sequence induction of anesthesia.\n Fifty patients, ASA 1-3, were randomly designated to receive one of three intravenous doses of rocuronium (0.6, 0.9, and 1.2 mg/kg), vecuronium (0.1 mg/kg), or succinylcholine (1.0 mg/kg). Patients were premedicated with midazolam and fentanyl, and received 2-7 mg/kg thiopental for induction of anesthesia. Sixty seconds after receiving a muscle relaxant, intubation of the trachea was attempted by a clinician who was blinded to the muscle relaxant administered. Neuromuscular monitoring was established before administration of the muscle relaxant. The time from injection of muscle relaxant until complete ablation of T1 (onset) and recovery of T1 to 25% (duration) were recorded. Tracheal intubating conditions were evaluated, and the presence or absence of fasciculations was noted.\n Onset times for patients receiving 0.9 mg/kg (75 +/- 28 s) and 1.2 mg/kg rocuronium (55 +/- 14 s), and succinylcholine (50 +/- 17 s) were similar. Onset times for the groups given 0.6 mg/kg rocuronium (89 +/- 33 s) and vecuronium (144 +/- 39 s) were significantly longer. Clinical duration of action was longest with 1.2 mg/kg rocuronium, similar with 0.6 and 0.9 mg/kg rocuronium, and vecuronium, and least with succinylcholine.\n There is a dose-dependent decrease in onset time with rocuronium. The onset times for the two larger doses of rocuronium were similar to that for succinylcholine, but clinical duration of action with rocuronium was significantly longer. The brief onset time achieved with rocuronium indicates that administration of 0.9-1.2 mg/kg is an acceptable alternative to succinylcholine for rapid-sequence induction of anesthesia.", "This study was designed to compare the tracheal intubating conditions during a rapid sequence induction of anaesthesia using rocuronium 0.6 (n = 61) or 1.0 mg.kg-1 (n = 130) or suxamethonium 1.0 mg.kg-1 (n = 127) as the neuromuscular blocking drugs. Anaesthesia was induced with fentanyl 1-2 micrograms.kg-1 and thiopentone 5 mg.kg-1 (median dose) and intubating conditions were assessed 60s after the administration of the neuromuscular blocking drug by an observer unaware of which drug had been given. Intubating conditions were graded on a three-point scale as excellent, good or poor, the first two being considered clinically acceptable. The study was carried out in two parts. At the end of the first part a comparison between the two doses of rocuronium was carried out when at least 50 patients had been enrolled in each group. The results showed the intubating conditions to be significantly superior with the 1.0 mg.kg-1 dose of rocuronium (p < 0.01). Final comparison between the 1.0 mg.kg-1 doses of rocuronium and suxamethonium showed no significant difference in the incidence of acceptable intubations (96 and 97%, respectively). The incidence of excellent grade of intubations was, however, significantly higher with suxamethonium (80% vs. 65%; p = 0.02). It is concluded that rocuronium 1.0 mg.kg-1 can be used as an alternative to suxamethonium 1.0 mg.kg-1 as part of a rapid sequence induction provided there is no anticipated difficulty in intubation. The clinical duration of this dose of rocuronium is, however, 50-60 min.", "The purpose of our study was to assess the onset and quality of muscle paralysis and intubation conditions with succinylcholine (Sch) or rocuronium (Roc) during rapid-sequence induction. Patients were randomly assigned to receive thiopental (5 mg/kg) and Sch (1.5 mg/kg) or thiopental (5 mg/kg) and Roc (1.2 mg/kg). The anesthesiologists performing the endotracheal intubation were blinded by standing with their back to the patient. Thirty seconds after drug administration, laryngoscopy was performed. Intubating conditions were scored, the clinical onset of apnea was noted, and a train-of-four monitor recorded data. All patients were ASA physical status I-III and scheduled for emergency procedures; both groups were demographically similar. Thirteen patients received Roc and 13 received Sch. There was no significant difference between the two groups in the number of patients receiving excellent intubating scores (P = 0.41) or in the combined number of patients receiving good and excellent scores (P = 1.0). There was no significant difference in time of onset of apnea for Sch (22+/-13 s) versus Roc (16+/-8s). The return of the first twitch response was significantly faster with Sch (5.05+/-2.5 min) compared with Roc (17.3+/-21.7 min) (P = 0.0001).\n In pediatric patients scheduled for emergency surgery, thiopental 5 mg/kg and rocuronium 1.2 mg/kg provided conditions for the completion of intubation in <60 s comparable to those provided by thiopental 5 mg/kg and succinylcholine 1.5 mg/kg. We conclude that rocuronium is a reasonable substitute for succinylcholine in children for rapid-sequence intubation when a rapid return to spontaneous respiration is not desired.", "When anesthesia is induced with propofol in elective cases, endotracheal intubation conditions are not different between succinylcholine and rocuronium approximately 60 s after the injection of the neuromuscular relaxant. In the present study, we investigated whether, in emergent cases, endotracheal intubation conditions obtained at the actual moment of intubation under succinylcholine differ from those obtained 60 s after the injection of rocuronium. One-hundred-eighty adult patients requiring rapid sequence induction of anesthesia for emergent surgery received propofol (1.5 mg/kg) and either rocuronium (0.6 mg/kg; endotracheal intubation 60 s after injection) or succinylcholine (1 mg/kg; endotracheal intubation as soon as possible). The time from beginning of the induction until completion of the intubation was shorter after the administration of succinylcholine than after rocuronium (median time 95 s versus 130 s; P < 0.0001). Endotracheal intubation conditions, rated with a 9-point scale, were better after succinylcholine administration than after rocuronium (8.6 +/- 1.1 versus 8.0 +/- 1.5; P < 0.001). There was no significant difference in patients with poor intubation conditions (7 versus 12) or in patients with failed first intubation attempt (4 versus 5) between the groups. We conclude that during rapid sequence induction of anesthesia in emergent cases, succinylcholine allows for a more rapid endotracheal intubation sequence and creates superior intubation conditions compared with rocuronium.", "Postoperative hoarseness (PH), sore throat (ST), and vocal cord injuries (VCI) are common complications after general anesthesia. Excellent endotracheal intubating conditions are associated with less laryngeal morbidity than good or poor intubating conditions. Thus, we tested the hypothesis that a rapid-sequence induction (RSI) with succinylcholine would lead to less PH and VCI than with rocuronium. In this prospective trial, 160 patients were randomized in 2 groups to receive thiopental 5.0 mg/kg, fentanyl 3.0 microg/kg, succinylcholine 1.0 mg/kg, or rocuronium 0.6 mg/kg during RSI. PH and ST were assessed at 24, 48, and 72 h after surgery, VCI were examined by stroboscopy in those patients who had PH >3 days. Excellent and clinically acceptable intubating conditions were significantly increased in the succinylcholine group compared with the rocuronium group: 57% versus 21% and 89% versus 59%, respectively (P < 0.001). The incidence and severity of PH, and VCI between the succinylcholine and the rocuronium groups did not differ significantly: PH: 50% versus 51% (P = 0.99) and VCI: 3% versus 1% (P = 0.98), respectively. Similar findings were found for ST, 39% versus 28% (P = 0.22), and postoperative myalgia, 39% versus 29% (P = 0.25), respectively. Intubating conditions were significantly better in the succinylcholine group compared with the rocuronium group. The incidence and severity of ST and myalgia were not increased in the patients receiving succinylcholine. However, the rate of PH and VCI was similar to the rocuronium group.", "In a blinded randomized study intubating conditions were compared at one min following intravenous induction with propofol and either suxamethonium 1.0 mg.kg-1, or rocuronium 0.6 mg.kg-1. Onset time to maximal twitch depression, % block at one minute and clinical duration (time to 25% recovery) were measured. Sixty children undergoing elective tonsillectomy were recruited. Onset time [42s (SD 11s)] and clinical duration [3.3 min (SD 1.0 min)] in the suxamethonium group was significantly (P < 0.001) less than in the rocuronium group [92s (41s)] and [24.2 min (6.6 min)] respectively. The median twitch height at one minute for suxamethonium was 0% (range 0-8%) and significantly greater (P < 0.001) at 5% (range 0-22%) for rocuronium. Despite this there was no difference in the intubating conditions at one minute with 25 excellent/5 good in the suxamethonium group and 27 excellent/3 good in the rocuronium group. We conclude that rocuronium 0.6 mg.kg-1 gives optimal intubating conditions at one minute in children.", "The time-course of action and tracheal intubating conditions of rocuronium and succinylcholine under intravenous anesthesia with propofol, alfentanil, and nitrous oxide were studied in 30 patients undergoing outpatient surgery. The neuromuscular effects of both drugs were quantified by recording the indirectly evoked twitch response of the adductor pollicis muscle after ulnar nerve stimulation (0.1 Hz, 0.2 ms supramaximal stimuli). Patients were given either 0.6 mg/kg rocuronium (n = 20) or 1 mg/kg succinylcholine (n = 10) intravenously. Sixty seconds after the administration of the muscle relaxant, the trachea was intubated and the intubating conditions were scored by a \"blinded\" assessor. Intubating conditions were not different (P = 0.34) between the rocuronium and succinylcholine groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with rocuronium. The depression of the twitch response to 5% of control value occurred in 0.8 +/- 0.1 min with 1 mg/kg succinylcholine and 1.2 +/- 0.5 min with 0.6 mg/kg rocuronium (P less than 0.01). The recovery of the twitch response to 25%, 75%, and 90% of its control value was shorter after succinylcholine (P less than 0.001) and occurred at 8.1 +/- 2.6, 10.3 +/- 3.9, 11.3 +/- 4.6 and 25.3 +/- 5.0, 33.1 +/- 5.9, 36.1 +/- 6.3 min after succinylcholine and rocuronium, respectively. Also the time required for spontaneous recovery from 25% to 75% of the control twitch response was significantly shorter (P less than 0.001) after succinylcholine (2.2 +/- 1.4 min) than after rocuronium (7.8 +/- 2.1 min). It is concluded that in spite of the pharmacodynamic differences between succinylcholine and rocuronium, the intubating conditions after administration of both compounds are similar and develop at the same rate.", "The onset time of neuromuscular blockade at the adductor pollicis (AP) is different among neuromuscular blocking drugs, but these discrepancies had never been studied at the orbicularis oculi (OO). The purpose of this study was to verify if the differences in onset time observed at the AP still existed at the OO and to score the intubating conditions using monitoring at the OO after five muscle relaxants. The study included 172 adults aged 18-75 yr. Anesthesia was induced with fentanyl and propofol. Atracurium (0.5 mg/kg), mivacurium (0.20 mg/kg), rocuronium (0.6 mg/kg), succinylcholine (1.0 mg/kg), or vecuronium (0.08 mg/kg) was injected by random allocation. Time to complete disappearance of the response at the OO was assessed visually after train-of-four stimulation of the facial nerve. Laryngoscopy was then performed, and intubating conditions were determined on a scale of 1-4. Results were based on 150 patients. Onset time at the OO was (mean +/- SD): succinylcholine (57 +/- 17 s) < mivacurium (99 +/-19 s) = rocuronium (99 +/- 47 s) < atracurium (129 +/-33 s) = vecuronium (135 +/- 38 s) (P < 0.05). Overall intubating conditions were excellent (84%), good (14%), poor (1.3%), impossible (0.7%), and were similar among the five groups. We conclude that differences in onset time of muscle relaxants observed at the AP were also found at the OO. Visual estimation of the response at the OO correctly predicted good-to-excellent intubating conditions in more than 90% of cases for all the currently available muscle relaxants.\n Onset time of neuromuscular blockade, as estimated visually at the orbicularis oculi, depends on the muscle relaxants given. Regardless of the relaxant used, intubating conditions at loss of orbicularis oculi are acceptable.", "Either succinylcholine or rocuronium administered after a hypnotic is the current technique for rapid-sequence induction. It is assumed that rocuronium administered before a hypnotic (Rocuronium-hypnotic sequence) may equally provide an acceptable intubation condition as well as a shorter period of apnea in rapid-sequence induction. We designed a prospective, randomized study to evaluate the effectiveness and safety of the technique in a similar rapid-sequence induction.\n Ninety adult patients receiving elective surgeries were enrolled in this study. In all patients the procedure in the study began with i.v. injection of fentanyl 2 micrograms/kg, followed by preoxygenation with 100% O2 for 2 min. Afterward, the patients were randomly allocated to 3 groups with each group consisting of 30 patients. In Rocuronium-thiopental (Ro-Th) group the patients received rocuronium 0.6 mg/kg and then thiopental 5 mg/kg; in Th-Ro group the patients received thiopental 5 mg/kg and then rocuronium 0.6 mg/kg; and in Thiopental-Succinylcholine (Th-Sx) group, the control group, the patients received thiopental 5 mg/kg and then succinylcholine 1 mg/kg. Laryngoscopy and endotracheal intubation were performed 60 s after the injection of the muscle relaxant. The intubation condition, the apneal time before laryngoscopy, the intubation time, and total apneal time were investigated and compared. Presence of injection pain, sense of paralysis, SpO2 less than 95% during induction, and any unexpected adverse event were also recorded.\n Six patients (1 in Ro-Th group, 2 in Th-Ro group, and 3 in Th-Sx group, respectively) were excluded from the study. The intubation conditions were acceptable in all patients of three groups who completed the study, and as to excellent intubation condition there was no difference between the three groups. In Ro-Th group both the apneal time before laryngoscopy (32.4 +/- 5.4 s) and total apneal time (48.5 +/- 11.0 s) were the shortest. Th-Ro group (53.2 +/- 5.8 and 67.5 +/- 8.3 s, respectively) and Th-Sx group (54.4 +/- 5.8 and 68.4 +/- 7.7 s, respectively) were similar in both aspects. With respect to intubation time there was no significant difference among the three groups. Five patients in Ro-Th group and one patient in Th-Sx group felt mild injection pain. Three patients in Ro-Th group were noted to have diminished breathing during induction, which was not recalled during enquiry in the postoperative visit. One patient in Ro-Th group saw a fall of SpO2 down below 95% (94% the minimal) during the apnea period.\n Compared with traditional hypnotic-rocuronium or hypnotic-succinylcholine sequence, rocuronium (0.6 mg)-thiopental sequence can provide a similar intubation condition but cause a much shorter apneal period in rapid-sequence induction. In carrying out recuronium-thiopental sequence induction, maintaining a patent infusion line is essential to avoid drug precipitation and awareness of muscular weakness as a result of ill-timed action of thiopental.", "To compare the clinical onset and duration of a combination of mivacurium and rocuronium with succinylcholine, and to determine the efficacy of this mixture for rapid tracheal intubation.\n Observer-blind prospective study.\n Teaching hospital.\n 70 ASA status I and II patients having general anesthesia for elective surgery.\n After induction of general anesthesia, patients randomly received succinylcholine 1.0 mg/kg, rocuronium 0.6 mg/kg, or a combination of rocuronium 0.6 mg/kg and mivacurium 0.15 mg/kg. Evoked muscular response at the adductor pollicis was measured by mechanomyography. The time from injection of muscle relaxant(s) to ablation of T1 (clinical onset) and recovery of T1 to 25% of control height (clinical duration) was recorded. Intubating conditions 45 seconds after administration of muscle relaxants were assessed. There was no significant difference in clinical onset time between succinylcholine (mean +/- SD, 47.4 +/- 6.5 seconds) and the combination of mivacurium-rocuronium (51.2 +/- 13.4 seconds). Intubating conditions with mivacurium-rocuronium were comparable to those of succinylcholine. The clinical duration of rocuronium 0.6 mg/kg (38.9 +/- 12.3 minutes) was prolonged by the addition of mivacurium (49.0 +/- 9.6 minutes).\n This combination of mivacurium and rocuronium is comparable to succinylcholine in both clinical onset time and quality of intubating conditions. When rapid onset of dense neuromuscular blockade and intermediate clinical duration is desirable, this mixture may be an acceptable alternative to succinylcholine.", "To compare changes in intraocular pressure (IOP) during rapid sequence induction and intubation following rocuronium, succinylcholine, and atracurium.\n Open-label, prospective, randomized study.\n Operating room at the Eye Foundation Hospital (University of Alabama at Birmingham)\n 45 ASA physical status I, II, and III patients, aged 18 to 65 years, scheduled for elective eye surgery with general anesthesia.\n Anesthesia was rapidly induced in unpremedicated patients with a fixed combination of midazolam 0.025 mg/kg, alfentanil 0.025 mg/kg, and propofol 1.5 mg/kg. Intubation was performed, as clinically indicated, approximately 60 seconds following administration of rocuronium 0.6 mg/kg, atracurium 0.5 mg/kg, or succinylcholine 1 to 1.5 mg/kg.\n Intraocular pressure was measured before induction of anesthesia (baseline), following anesthesia induction and administration of muscle relaxant (before intubation), and after intubation. The percent change in IOP from baseline was significantly decreased in the rocuronium group compared with the succinylcholine group (p = 0.046) before intubation. This trend continued after intubation, but the difference was no longer significant (p = 0.070). Intubation scores for rocuronium and succinylcholine groups were similar, and both scores were superior to that for the atracurium group (p = 0.002).\n Intraocular pressure can be controlled during emergency induction of anesthesia and intubation with adequate depth of anesthesia and muscle relaxation. Rocuronium, succinylcholine, and atracurium all provided sufficient muscle relaxation to achieve successful intubation and no increase in IOP. However, rocuronium 0.6 mg/kg provided significantly better intubating conditions compared with atracurium, and it resulted in a significantly greater decrease in IOP compared with baseline than succinylcholine.", "We have compared the effect of rocuronium and succinylcholine on intraocular pressure (IOP) during rapid sequence induction of anaesthesia using propofol and fentanyl, in a randomized double-blind study. We studied 30 adult patients, allocated to one of two groups. Anaesthesia was induced with fentanyl 2 micrograms kg-1 and propofol until loss of verbal response. This was followed by succinylcholine 1.5 mg kg-1 (group S; n = 15) or rocuronium 0.9 mg kg-1 (group R; n = 15). Laryngoscopy was performed 60 s later. IOP, mean arterial pressure (MAP) and heart rate (HR) were measured before induction, immediately before intubation and every minute after intubation for 5 min. A Keeler Pulsair air impulse tonometer was used to measure IOP and the mean of two readings obtained in the right eye at each measurement time was recorded. Intubating conditions were evaluated according to a simple scoring system. IOP in the succinylcholine group was significantly greater than that in the rocuronium group (mean 21.6 (SEM 1.4) mm Hg vs 13.3 (1.4) mm Hg; P < 0.001). Intubating conditions were equally good in both groups. We conclude that with rapid sequence induction of anaesthesia using propofol and fentanyl, rocuronium did not cause as great an increase in IOP as succinylcholine and may be an alternative in open eye injury cases.", "To determine if, using a variation of the \"timing\" principle, 0.6 mg/kg of rocuronium can achieve an onset time and intubating conditions similar to those achieved with succinylcholine.\n Prospective, randomized, double-blind clinical comparison.\n Operating room in a university medical center.\n 42 ASA physical status I and II patients undergoing general anesthesia for elective surgery.\n All patients were fitted with a Grass FT-10 force transducer attached to the thumb. Supramaximal stimulation was applied to the ulnar nerve with a variable current peripheral nerve stimulator. 22 patients (succinylcholine group) received a placebo bolus injection followed 20 seconds later by thiopental 4 to 5 mg/kg and succinylcholine 1 mg/kg; 20 additional patients (rocuronium group) received a bolus dose of rocuronium 0.6 mg/kg followed 20 seconds later by thiopental 4 to 5 mg/kg and a placebo bolus injection.\n We measured the onset time from administration of the muscle relaxant to 95% twitch reduction and assessed the quality of intubating conditions 60 seconds after the induction of anesthesia. There was a significant difference in the mean onset time of rocuronium (72 sec) versus succinylcholine (42 sec, p < 0.0001). However, there was no significant difference in intubating conditions 60 seconds after administration of thiopental.\n Rocuronium given 20 seconds prior to thiopental provides intubating conditions equivalent to thiopental-succinylcholine for rapid-sequence inductions, circumventing rocuronium's longer onset time to 95% neuromuscular blockade.", "The use of suxamethonium in children is associated with undesirable side effects. The synergistic effect of a rocuronium-mivacurium combination can be considered as an acceptable alternative to suxamethonium in clinical practice. The calculated ED50 of the rocuronium-mivacurium mixture was only 62% of the predicted value assuming a purely additive interaction. The use of this combination has not been evaluated in children. In this two-part study, we assessed the intubating conditions and pharmacodynamics of suxamethonium, rocuronium, mivacurium or a rocuronium-mivacurium combinations in children. We studied 120 ASA I children of both sexes, aged 3-10 yr. Children were premedicated with trimeprazine 2 mg kg-1 orally, and received fentanyl 2 micrograms kg-1 and propofol 2 mg kg-1 for induction of anaesthesia. They were allocated randomly to receive one of the following drugs or drug combinations: suxamethonium 1.0 mg kg-1, mivacurium 0.2 mg kg-1, rocuronium 0.6 or 0.9 mg kg-1, mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 or mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1. In part 1, 60 s after administration of the neuromuscular blocking drug or drug combination, tracheal intubation was performed in 60 children by mimicking rapid sequence induction, and intubating conditions were evaluated by a blinded investigator according to a standard score. In part 2, neuromuscular monitoring was established before administration of neuromuscular blocking agent(s) and the time from injection of drug or drug combination until complete ablation of T1 (onset) and recovery of T1 to 25% (duration) were recorded in another 60 children. The frequency of distribution of excellent or good intubating conditions in the higher dose of rocuronium and the combination groups were similar to those in the suxamethonium group, but significantly different (P < 0.05) from those in the mivacurium group. Mean onset time was faster in the suxamethonium (55.1 (SD 11.4) s), rocuronium 0.9 mg kg-1 (70.5 (37.7) s), mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 (67 (35.9) s) and mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1 (55 (26.7) s) groups compared with the mivacurium 0.2 mg kg-1 (116 (26.8) s) and rocuronium 0.6 mg kg-1 (97.9 (29) s) groups. This study demonstrated that the combination of rocuronium 0.45 mg kg-1 and mivacurium 0.15 mg kg-1 could possibly be considered as an acceptable alternative to suxamethonium when rapid sequence induction of anaesthesia is indicated in children because it provides uniform excellent intubating conditions and complete neuromuscular block in < 60 s.", "We have assessed intubating conditions after administration of Org 9426 (rocuronium) 600 micrograms kg-1 at 60 or 90 s in groups of 20 patients anaesthetized with thiopentone, nitrous oxide in oxygen and small doses of fentanyl, and compared the data with those obtained after suxamethonium 1 mg kg-1 in similar groups of patients. The influence of prior suxamethonium administration on the potency of Org 9426 was studied also by constructing a dose-response curve. Intubating conditions after Org 9426 were found to be clinically acceptable (good or excellent) in 95% of patients at 60 s and in all patients at 90 s and in all patients at both times after suxamethonium. The average time for the onset of block following Org 9426 at this dose was 89 s (which is shorter than with any of the currently available non-depolarizing neuromuscular blocking drugs); the duration of clinical relaxation (25% recovery of twitch height) 30 min. Prior administration of suxamethonium did not appear to influence the potency of Org 9426.", "To compare the onset and offset time (clinical duration), and intubating conditions obtained with rocuronium bromide 0.6 mg/kg and succinylcholine 1.0 mg/kg after induction with propofol and fentanyl; and to compare rocuronium with atracurium for maintenance during propofol anesthesia.\n Prospective, open-label, parallel group comparative, randomized study.\n Operating rooms of a university hospital.\n 30 ASA physical status I and II adult patients scheduled for elective surgeries with general anesthesia.\n Patients premedicated with midazolam 2 mg were anesthetized with fentanyl 2 microg/kg followed by propofol 2.5 mg/kg and muscle relaxants. Group 1 (n = 15) received succinylcholine 1.5 mg/kg and Group 2 (n = 16) received rocuronium bromide 0.6 mg/kg. Intubation was performed 60 seconds after the administration of muscle relaxant. Patients in Group 1 received atracurium and patients in Group 2 received rocuronium for maintenance if required.\n The ease of intubation was scored using a scale of 1 to 4. Onset and offset time monitored with evoked twitch response of the adductor pollicis were recorded.\n Intubation was successful in all patients and there was no difference in scores between the two groups. Although onset time was shorter with succinylcholine than with rocuronium, neuromuscular blockade was successfully antagonized in both groups, and the recovery profile was not different between the two groups.\n Rocuronium bromide at a dose of 0.6 mg/kg, when used with propofol and fentanyl for induction, provides intubating conditions similar to succinylcholine 1.0 mg/kg at 1 minute. The actual onset time and offset time, however, are significantly longer with rocuronium. There was no difference between atracurium and rocuronium as a maintenance drug. Rocuronium is suitable for surgical procedures greater than 30 minutes, eliminating the need for an additional relaxant to succinylcholine.", "To compare the pharmacodynamics of two commonly recommended doses of rocuronium bromide (0.7 mg/kg and 0.9 mg/kg) and succinylcholine (1.5 mg/kg) when used for rapid-sequence intubation.\n Prospective, double-blind, randomized study.\n Operating rooms at a university hospital.\n 45 ASA physical status I and II adult patients scheduled for elective surgeries under general anesthesia.\n Nonpremedicated patients were anesthetized with fentanyl 2 mcg/kg followed by thiopental sodium 4 to 5 mg/kg and muscle relaxant using rapid-sequence technique. Group 1 (n = 15) received rocuronium bromide 0.7 mg/kg. Group 2 (n = 16) received rocuronium bromide 0.9 mg/kg, and Group 3 (n = 14) received succinylcholine 1.5 mg/kg. Intubation was performed 60 seconds after the administration of muscle relaxant.\n The case of intubation was scored using a scale of 1 to 4. Blood pressure and heart rate were measured beginning one minute before induction of anesthesia up to 5 minutes after intubation. Intubation scores were similar in groups 2 and 3 and were noted as good or excellent in all patients. Group 1 displayed a significantly lower intubation score than the other two groups; 60% were rated as poor. No significant differences in hemodynamic data were seen among the three groups.\n Rocuronium bromide at a dose of 0.9 mg/kg provides intubating conditions similar to succinylcholine 1.5 mg/kg at 1 minute. Intubating conditions at 1 minute following a 0.7 mg/kg dose of rocuronium are not as good as those following a 0.9 mg/kg dose of rocuronium or a 1.5 mg/kg dose of succinylcholine.", "Rocuronium (ORG 9426) has been shown to have an onset of action more rapid than other nondepolarizing neuromuscular blocking agents and to provide intubating conditions similar to those of succinylcholine 60-90 s after administration. We compared the intubating conditions and hemodynamic changes after the administration of rocuronium 0.6 mg kg(-1) and lidocaine 1.5 mg kg(-1) with rocuronium alone and succinylcholine 60 and 90 s after administration.\n One hundred and twenty-five adult patients of ASA physical status I or II scheduled for elective surgery were randomly divided into five groups. After propofol administration in all patients, patients in group Su (succinylcholine), group R60 (rocuronium) and group RL60 (rocuronium-lidocaine) were intubated within 60 s, while groups RL90 and R90 were intubated 90 s after the administration of rocuronium and succinylcholine. Laryngoscopy was performed and intubating conditions were graded by an experienced anesthetist blind to the muscle relaxant allocation.\n In this study, groups Su, RL60, R90 and RL90 had similar intubation scores, which were significantly better than that for group R60. Heart rate did not increase after intubation in groups Su, RL60 and RL90.\n The combination of lidocaine (1.5 mg kg(-1)) and low-dose rocuronium (0.6 mg kg(-1)) along with propofol is clinically equivalent to succinylcholine, improves intubating conditions in 60 s and effectively blocks increases in heart rate after intubation.", "nan", "Tracheal intubating conditions and neuromuscular effects of succinylcholine, rocuronium, and mivacurium were studied in 100 healthy women undergoing outpatient laparoscopic surgery. After a standardized fentanyl-thiopental induction, tracheal intubation was facilitated with succinylcholine 1 mg/kg in Groups I (n = 23) and II (n = 25), rocuronium 0.6 mg/kg in Group III (n = 27), or mivacurium 0.2 mg/kg in Group IV (n = 25). If clinically indicated, bolus doses of rocuronium 5-10 mg (Groups I and III) or mivacurium 2-4 mg (Groups II and IV) were administered during the maintenance period. Anesthesia was maintained with desflurane and nitrous oxide 60% in oxygen. At the end of the surgery, residual neuromuscular block was reversed with edrophonium 0.5 mg/kg and atropine 10 micrograms/kg, if needed. The neuromuscular function was assessed using electromyography with a train-of-four mode of stimulation every 10 s at the wrist. Intubating conditions 90 s after succinylcholine and rocuronium were significantly better than after mivacurium. The onset time (from the end of injection until 95% suppression of the first twitch [T1]) for succinylcholine (63 +/- 21 s and 62 +/- 17 s in Groups I and II, respectively) were significantly shorter than for rocuronium (158 +/- 76 s) or mivacurium (210 +/- 93 s). Moreover, the onset times for rocuronium were significantly shorter than mivacurium. The recovery times (of T1 to 25% of the control value) were significantly shorter with succinylcholine and mivacurium than rocuronium. Significantly fewer patients needed reversal of residual neuromuscular blockade after mivacurium compared to rocuronium. One patient in Group I and six patients in Group IV displayed erythema on the upper body. Postoperative myalgia were experienced by 16% of the patients in Groups I and II compared to none in Groups III and IV. There was on difference in the incidence of postoperative nausea and vomiting among the four groups. In conclusion, rocuronium appears to be an acceptable alternative to succinylcholine for tracheal intubation. However, rocuronium's longer duration of action increases the need for reversal drugs. When rapid tracheal intubation is unnecessary, mivacurium is also an acceptable alternative to succinylcholine and is associated with a more rapid spontaneous recovery than rocuronium.", "Rocuronium has an onset of action more rapid than other non-depolarizing neuromuscular blocking agents, but it is unclear whether it and succinylcholine give equivalent intubating conditions during rapid-sequence induction of anaesthesia. We performed this study to answer the question--are there clinically relevant differences between the use of rocuronium and succinylcholine to secure acceptable intubating conditions during rapid-sequence induction of anaesthesia with propofol?\n Anaesthesia was induced using propofol 2.5 mg/kg in 349 ASA physical status grade I-IV patients who were undergoing either elective or emergency surgery. Propofol was followed immediately by either rocuronium 0.6 or 1 mg/kg or succinylcholine 1.0 mg/kg (randomly selected). Fifty seconds after the end of muscle relaxant injection laryngoscopy was performed and intubating conditions were graded by an experienced anaesthetist blind to the muscle relaxant allocation. This study design was selected so that a 10% difference in clinically acceptable intubating conditions between drugs would be detectable.\n In this setting rocuronium 1.0 mg/kg provided superior intubating conditions compared with rocuronium 0.6 mg/kg. The incidence of clinically acceptable intubating conditions with rocuronium 1.0 mg/kg and succinylcholine 1.0 mg/kg was 93.2% and 97.1% respectively, the difference being -3.9% (95% C.I. -9.7% to 1.9%).\n Rocuronium 1.0 mg/kg given along with propofol in a rapid-sequence induction of anaesthesia is clinically equivalent to succinylcholine 1.0 mg/kg.", "To evaluate the effects of priming doses of rocuronium on the duration of priming interval and on the outcome of priming sequence using rocuronium-atracurium combination.\n Three phase, randomized, controlled study.\n Inpatient anesthesia in a university hospital.\n 144 ASA physical status I and II patients, 19 to 57 years of age, weighing 50 to 90 kg, and undergoing low-risk elective surgery.\n Phase I, two equal groups (n = 12) of adult patients anesthetized with propofol, fentanyl, and nitrous oxide (N2O), received a priming dose of rocuronium 0.1 mg/kg or vecuronium 0.015 mg/kg. Phase II included six equal groups (n = 12): Groups 1, 2, and 3 received a priming dose of rocuronium 0.1 mg/kg and atracurium 0.42 mg/kg for intubation. The priming intervals were, respectively, 1, 1.5, or 2 minutes in Groups 1, 2, and 3. Groups 4, 5, and 6 received, respectively, a bolus dose of rocuronium 0.6 mg/kg, atracurium 0.5 mg/kg, or succinylcholine 1 mg/kg. Intubation was performed at maximum block. Phase III included four equal groups (n = 12). A priming dose of rocuronium 0.1 mg/kg (Group 1) or a placebo (Groups 2, 3, and 4) was given to awake patients. Anesthesia was induced during the one-minute priming interval. Intubating doses of atracurium 0.42 mg/kg, rocuronium 0.6 mg/kg, atracurium 0.5 mg/kg, or succinylcholine 1 mg/kg were given to Groups 1, 2, 3, and 4, respectively. Intubation was attempted 1 minute after intubating doses were administered.\n Adductor pollicis response to train-of-four stimulation was recorded mechanically in Phases I and II only. The priming interval after rocuronium 0.1 mg/kg was in the range of 1 to 2 minutes. Priming doses of rocuronium resulted in significant acceleration in the onset time of intubating doses of atracurium, irrespective of the duration of the priming interval. The onset times [mean (SD)] following rocuronium-atracurium sequence in Groups 1, 2, and 3 were, respectively, 67 (17), 73 (14), and 66 (18) seconds and were comparable with the onset of bolus doses of rocuronium and succinylcholine. In Phase II, good to excellent intubating conditions were obtained in 41% to 58% of patients included in Groups 1 through 5. Excellent to good intubating conditions were obtained in all patients (100%) who received succinylcholine. In Phase III, good to excellent intubating conditions were obtained in 91% of patients who received recuronium-atracurium sequence. Symptoms of muscle weakness were not reported.\n Priming doses of recuroniums 0.1 mg/kg reduce the priming interval to 1 minute, allow early induction of anesthesia, eliminate patient discomfort, and accelerate the onset time of altracurium with intubating conditions comparable with succinylcholine and rocuronium.", "To compare 4 different anesthesia induction protocols, in a simulated model of rapid-sequence induction, in controlled hypertensive patients.\n Prospective, randomized, double-blind, clinical investigation.\n Large metropolitan university hospital.\n 120 ASA II-III adult hypertensive patients.\n Patients were allocated to 4 groups at random. After preoxygenation for 3 minutes, induction and tracheal intubation was performed in a 30 degrees head-up position. Thiopental (5-7 mg/kg) was the induction agent. Study groups were as follows: group LS (n = 30), lidocaine (1.5 mg/kg) and succinylcholine (1 mg/kg); group LR (n = 30), lidocaine (1.5 mg/kg) and rocuronium (1 mg/kg); group RS (n = 30), remifentanil (1 microg/kg) and succinylcholine (1 mg/kg); group RR (n = 30), remifentanil (1 microg/kg) and rocuronium (1 mg/kg). Patients were intubated 60 seconds after administration of muscle relaxant.\n Hemodynamic data were obtained before induction (baseline), after induction, at intubation, and at 1, 3, 5, and 10 minutes after intubation. More than 20% change in blood pressure and heart rate was considered significant.\n Systolic and mean arterial blood pressures at intubation and 1 and 3 minutes after intubation were higher in group LS compared with groups RS and RR (P < 0.01). Mean arterial blood pressure decreased after induction in groups LS, LR, and RR, but increased at intubation and 1 minute after intubation in groups LS and LR (P < 0.01). Mean arterial blood pressure was similar at all measurement intervals in group RS. The median area under the systolic, mean, and diastolic blood pressure time curves was higher in groups LS and LR compared with groups RS and RR (P < 0.05 and P < 0.01).\n Remifentanil is a better adjunct for attenuation of the response to laryngoscopy and intubation compared with lidocaine, whereas remifentanil-succinylcholine combination appears to be more beneficial in terms of hemodynamic stability in hypertensive patients.", "To compare succinylcholine (S) and rocuronium (R) used for endotracheal intubation, and to assess the possible action of S on subsequently administered R.\n Double-blind, randomized, phase III study.\n University Medical Center.\n 24 ASA physical status I and II patients, ages 28 to 65, undergoing general anesthesia for abdominal procedures.\n Double-blind administration of R 600 mcg/kg (Group A) or S 1 mg/kg was achieved with open label R 150 mcg/kg. Standardized general anesthetic technique with sodium thiopental, fentanyl, and nitrous oxide in oxygen was administered.\n Neuromuscular junction was tested by ulnar nerve stimulation and mechanomyograph. Intubation was attempted at 80% first twitch depression of train-of-four. Heart rate and blood pressure were recorded throughout. Onset times were 74 +/- 37 seconds for S and 130 +/- 46 seconds for R. Intubation times were 76 +/- 29 seconds for S and 85 +/- 23 seconds for R (no significant difference). Good to excellent intubation conditions were achieved in both groups. S given prior to R decreased onset time and increased duration of R, when compared with R given alone. No drug related cardiovascular events were noted.\n Rapid intubation conditions can be obtained after both S and R. Given its overall safety profile, R can be used when S is contraindicated, or in healthy patients with no apparent difficult airway, when procedures are expected to last more than 25 minutes." ]

[ "17214932" ]

[ "[Effects of Salvia miltiorrhiza on serum levels of inflammatory cytokines in patients with severe acute pancreatitis]." ]

[ "To study the effects of Salvia miltiorrhiza on serum levels of cytokines including interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in patients with severe acute pancreatitis (SAP).\n Thirty-six SAP patients were randomly divided into Salvia miltiorrhiza-treated group and non-Salvia miltiorrhiza-treated group with eighteen patients in each group. Fourteen age-matched healthy volunteers were assigned to control group. Serum levels of IL-6, IL-8, and TNF-alpha were tested within 24 hours of admission and 7 days after admission.\n Compared with those of the healthy volunteers, serum levels of the three cytokines of the SAP patients were significantly elevated (P<0.05). Serum levels of the three cytokines were significantly decreased in both Salvia miltiorrhiza-treated group and non-Salvia miltiorrhiza-treated group after 7-day treatment (P<0.05). The declining of the serum levels of the three cytokines in Salvia miltiorrhiza-treated group was more obvious than that in non-Salvia miltiorrhiza-treated group.\n Salvia miltiorrhiza can treat SAP patients by reducing the serum levels of IL-6, IL-8, and TNF-alpha." ]

[ "9922309", "10648454", "10333200", "15825069", "7615189", "11227650", "16966711", "16377775", "7768364", "8724022", "7835575", "15362028", "19109962", "12622760", "15362027", "17211699", "17206696", "11413109", "18727929", "12171964", "2572495" ]

[ "Oral budesonide for prevention of postsurgical recurrence in Crohn's disease. The IOIBD Budesonide Study Group.", "Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI.", "Low-dose budesonide treatment for prevention of postoperative recurrence of Crohn's disease: a multicentre randomized placebo-controlled trial. German Budesonide Study Group.", "Ornidazole for prophylaxis of postoperative Crohn's disease recurrence: a randomized, double-blind, placebo-controlled trial.", "Prophylactic mesalamine treatment decreases postoperative recurrence of Crohn's disease.", "[Azathioprine and 5-ASA in the prevention of postoperative recurrence of Crohn's disease].", "Adverse events in clinical trials with azathioprine and mesalamine for prevention of postoperative recurrence of Crohn's disease.", "Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn's disease: a randomised, double blind, placebo controlled GETAID trial.", "Controlled trial of metronidazole treatment for prevention of Crohn's recurrence after ileal resection.", "Placebo-controlled clinical trial of mesalazine in the prevention of early endoscopic recurrences after resection for Crohn's disease. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID).", "Mesalamine in the prevention of endoscopic recurrence after intestinal resection for Crohn's disease. Italian Cooperative Study Group.", "Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn's disease.", "Infliximab prevents Crohn's disease recurrence after ileal resection.", "Two mesalazine regimens in the prevention of the post-operative recurrence of Crohn's disease: a pragmatic, double-blind, randomized controlled trial.", "Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial.", "Failure of Synbiotic 2000 to prevent postoperative recurrence of Crohn's disease.", "Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn's disease after lleo-caecal resection.", "Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn's disease.", "Therapy of metronidazole with azathioprine to prevent postoperative recurrence of Crohn's disease: a controlled randomized trial.", "Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG.", "Postoperative recurrence of Crohn's disease in relation to radicality of operation and sulfasalazine prophylaxis: a multicenter trial." ]

[ "Prevention of postoperative recurrence after resection for Crohn's disease (CD) would be of great clinical benefit. The efficacy of oral budesonide for prevention of endoscopic recurrence was evaluated in patients undergoing resection for ileal or ileocecal CD.\n Sixty-three patients received budesonide and 66 received placebo in a double-blind, randomized trial with parallel groups. Ileocolonoscopy, including biopsy, was performed after 3 and 12 months. Indications for surgery were fibrostenosis (78 patients), disease activity (41), and other reasons (10).\n The frequency of endoscopic recurrence did not differ between the groups at 3 and 12 months. In patients with disease activity as indication for surgery, the endoscopic recurrence rate at the anastomosis was lower in the budesonide group at 3 months, although not significantly (21% vs. 47%; P = 0.11), and at 12 months (32% vs. 65%; P = 0.047). There was no such difference with respect to fibrostenosis as indication for surgery. No differences in adverse event patterns were found between the two groups.\n Oral budesonide, 6 mg daily, offered no benefit in prevention of endoscopic recurrence after surgery for ileal/ileocecal fibrostenotic CD but decreased the recurrence rate in patients who had undergone surgery for disease activity.", "This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection.\n In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model.\n Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003).\n Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.", "Endoscopic recurrence of Crohn's disease frequently occurs within weeks after 'curative' operation. Treatment with 3 x 1 mg oral pH-modified release budesonide was tried to prevent postoperative recurrence.\n A multicentre randomized double-blind placebo-controlled trial of 1 year duration was performed.\n Departments of surgery, endoscopy and pathology of three university hospitals participated in the trial.\n Patients with Crohn's disease who underwent ileal and/or colonic resection and whose anastomosis was accessible to colonoscopy were admitted to the study. Of the 88 randomized patients, 83 patients were included in the efficacy analysis (budesonide n = 43, placebo n = 40). Treatment was started within 2 weeks after surgery.\n Colonoscopy was performed 3 and 12 months postoperatively. The anastomosis and the adjacent bowel were evaluated by endoscopy and histology. For follow-up of the clinical course of the disease the Crohn's disease activity index (CDAI) was used.\n The primary outcome variable was recurrence of Crohn's disease based on endoscopic findings. Secondary efficacy variables were histology scores, CDAI, time-to-failure and global judgement of well-being of the patient.\n The recurrence rate after 1 year (endoscopic and/or clinical) was 57% (20/35) in the budesonide group and 70% (19/27) in the placebo group (n.s.). Mean time-to-failure was 196 days under budesonide and 154 days under placebo (n.s.). Median CDAI (relapse 19% vs. 28%) and global patients' judgement at the end of treatment (bad 5% vs. 15%) was slightly in favour of budesonide. One patient in each group discontinued the trial because of adverse events. Potentially steroid-related side effects were reported more frequently in the placebo than in the budesonide group (32% vs. 17%) (n.s.).\n Although the effect of budesonide was altogether positive in almost all variables studied in this trial (e.g. endoscopic and histopathological score, time-to-failure, CDAI, patients' global judgement and rate of side effects), this increase in efficacy was small and the power for detecting differences versus placebo was too low to be statistically significant. According to these results, low-dose oral budesonide cannot be recommended to be used for the prevention of postoperative relapse in Crohn's disease.", "Crohn's disease almost inevitably recurs after ileocolonic resection, and effective prophylactic therapy has not been identified. We investigated the efficacy and safety of ornidazole, a nitroimidazole antibiotic, for the prevention of clinical recurrence of Crohn's disease after curative ileocolonic resection in a placebo-controlled double-blind clinical trial.\n Eighty patients were randomized to ornidazole 1 g/day or placebo started within 1 week of resection and continued for 1 year. The primary end point was the proportion of patients with clinical recurrence at 1 year. Secondary end points were endoscopic recurrence at 3 months and 12 months after resection.\n Two patients in the ornidazole group withdrew consent and were not dosed. Ornidazole significantly reduced the clinical recurrence rate at 1 year from 15 of 40 (37.5%) patients in the placebo group to 3 of 38 (7.9%) patients in the ornidazole group (Fisher exact test, 8.03; P = .0046; odds ratio, 0.14; 95% confidence interval, 0.037-0.546). Ornidazole reduced endoscopic recurrence at 12 months from 26 of 33 (79%) in the placebo group to 15 of 28 (53.6%) in the ornidazole group (chi2 , 4.37; P = .037; odds ratio, 0.31; 95% confidence interval, 0.10-0.94). Endoscopic recurrence at 3 and 12 months predicted clinical recurrence. Significantly more patients in the ornidazole group dropped out from the study because of side effects (P = .041).\n Ornidazole 1 g/day is effective for the prevention of recurrence of Crohn's disease after ileocolonic resection.", "Recurrence of Crohn's disease frequently occurs after surgery. A randomized controlled trial was performed to determine if mesalamine is effective in decreasing the risk of recurrent Crohn's disease after surgical resection is performed.\n One hundred sixty-three patients who underwent a surgical resection and had no evidence of residual disease were randomized to a treatment group (1.5 g mesalamine twice a day) or a placebo control group within 8 weeks of surgery. The follow-up period was a maximum of 72 months.\n The symptomatic recurrence rate (symptoms plus endoscopic and/or radiological confirmation of disease) in the treatment group was 31% (27 of 87) compared with 41% (31 of 76) in the control group (P = 0.031). The relative risk of developing recurrent disease was 0.628 (90% confidence interval, 0.40-0.97) for those in the treatment group (P = 0.039; one-tail test) using an intention-to-treat analysis and 0.532 (90% confidence interval, 0.32-0.87) using an efficacy analysis. The endoscopic and radiological rate of recurrence was also significantly decreased with relative risks of 0.654 (90% confidence interval, 0.47-0.91) in the effectiveness analysis and 0.635 (90% confidence interval, 0.44-0.91) in the efficacy analysis. There was only one serious side effect (pancreatitis) in subjects in the treatment group.\n Mesalamine (3.0 g/day) is effective in decreasing the risk of recurrence of Crohn's disease after surgical resection is performed.", "Recurrence of Crohn's disease (CD) lesions in the neo-ileum after apparently curative resection frequently occurs after surgery. The most appropriate prophylactic treatment has not been clearly defined. This study evaluated the efficacy of 5-ASA and azathioprine in decreasing postoperative recurrence and analysed the presence of variables associated with recurrence. Thirty-nine patients (mean age 32.8 years, range 18-61) with a history of ileal or ileocecal surgical resection were studied. They received 5-ASA (3 mg/day) or azathioprine (50 mg/day) immediately after the operation and for 2 years thereafter. Patients were followed clinically (Crohn's disease activity index) and serologically every 3 months and by imaging methods every 6 months. The latter included colonoscopy with ileoscopy and if not available, small bowel barium or ultrasonographic study. Laboratory tests included ESR, C-reactive protein, white blood cell and platelet count, fibrinogen and albumin. The end-point evaluated included clinical recurrence (CR), serological recurrence (SR: alteration of at least three of the above-mentioned variables) and morphologic recurrence (MR: endoscopic recurrence > 1 according to Rutgeerts score or radiological or ultrasonographic recurrence). Eighteen patients received azathioprine and 21 received 5-ASA. Thirty-four patients were evaluated. The cumulative proportion of patients with recurrence was 29% (CR), 35% (SR) and 50% (MR). Statistical analysis did not show significant differences between the two groups. Twenty-seven patients completed the 2-year study (11 in the azathioprine group and 16 in the 5-ASA group). Crude relapse rates were 37% (CR), 44% (SR) and 69% (MR) in the 5-ASA group and 36% (CR), 45% (SR) and 64% (MR) in the azathioprine group. No statistically significant differences were observed between groups. No variables associated with recurrence were detected. In conclusion, treatment does not prevent a high percentage of postsurgical recurrence. 5-ASA (3 g/day) and azathioprine (50 mg/day) showed similar efficacy in the prevention of recurrence.", "nan", "Early endoscopic recurrence is frequent after intestinal resection for Crohn's disease. Bacteria are involved, and probiotics may modulate immune responses to the intestinal flora. Here we tested the probiotic strain Lactobacillus johnsonii LA1 in this setting.\n This was a randomised, double blind, placebo controlled study. Patients were eligible if they had undergone surgical resection of <1 m, removing all macroscopic lesions within the past 21 days. Patients were randomised to receive two packets per day of lyophilised LA1 (2 x 10(9) cfu) or placebo for six months; no other treatment was allowed. The primary endpoint was endoscopic recurrence at six months, with grade >1 in Rutgeerts' classification or an adapted classification for colonic lesions. Endoscopic score was the maximal grade of ileal and colonic lesions. Analyses were performed primarily on an intent to treat basis.\n Ninety eight patients were enrolled (48 in the LA1 group). At six months, endoscopic recurrence was observed in 30/47 patients (64%) in the placebo group and in 21/43 (49%) in the LA1 group (p = 0.15). Per protocol analysis confirmed this result. Endoscopic score distribution did not differ significantly between the LA1 and placebo groups. There were four clinical recurrences in the LA1 group and three in the placebo group.\n L johnsonii LA1 (4 x 10(9) cfu/day) did not have a sufficient effect, if any, to prevent endoscopic recurrence of Crohn's disease.", "New lesions recur within weeks to months after ileal resection and ileocolonic anastomosis for Crohn's ileitis. A double-blind controlled trial was performed using metronidazole to prevent recurrence after ileal resection.\n Sixty patients who underwent curative ileal resection and primary anastomosis were included within 1 week after surgery. Thirty patients received metronidazole (20 mg/kg body wt) daily for 3 months, and 30 patients received placebo. Treatment was then discontinued. Nine patients dropped out during treatment, 7 in the metronidazole group and 2 in the placebo arm.\n At 12 weeks, 21 of 28 patients (75%) in the placebo group had recurrent lesions in the neoterminal ileum as compared with 12 of 23 patients (52%) in the metronidazole group (P = 0.09). The incidence of severe endoscopic recurrence was significantly reduced by metronidazole (3 of 23; 13%) as compared with placebo (12 of 28; 43%; P = 0.02). Patients in the metronidazole arm had more frequent side effects. Metronidazole therapy statistically reduced the clinical recurrence rates at 1 year (4% vs. 25%). Reductions at 2 years (26% vs. 43%) and 3 years (30% vs. 50%) were not significant.\n Metronidazole therapy for 3 months decreases the severity of early recurrence of Crohn's disease in the neoterminal ileum after resection and seems to delay symptomatic recurrence.", "Endoscopic postoperative recurrences occur early after 'curative' surgery for Crohn's disease. Pentasa has been shown to be effective in the maintenance treatment of quiescent Crohn's disease. The aim of this study was to test the efficacy of a 12-week oral intake of Claversal in the prevention of endoscopic recurrences after 'curative' resection for ileal, colonic or ileocolonic Crohn's disease. We conducted a multicentre double-blind controlled trial comparing Claversal (1g tid) with placebo, starting within 15 days after surgery. The macroscopic normality of the two anastomotic segments was assessed at surgery. Patients were clinically and biologically evaluated twice (6-week interval), and colonoscopy was performed at 12 weeks. Endoscopic relapse was defined by any anastomotic ulcerations or stenosis and staged according to a four-grade score.\n Between May 1989 and May 1991 12 centres included 126 patients, 70 women and 56 men, aged 33 +/- 12 years (range 16-70) in the study. Disease locations were ileal, colonic and ileocolonic in 45, 6 and 49%, respectively. Claversal and placebo groups were similar at inclusion, except for ESR (37 +/- 26 vs. 27 +/- 23 mm/h in the Claversal and placebo groups, respectively; P < 0.05). Nine patients were withdrawn from the study. Adverse reactions occurred only in six patients. Five patients were excluded for protocol violation. Finally, 106 patients could be evaluated at 12 weeks (55 Claversal and 51 placebo). An endoscopic relapse was observed in 50% and 63% of the Claversal and placebo groups, respectively (P = 0.16), with a similar grade distribution. Claversal was well tolerated.\n Our study confirms that a large proportion of endoscopic recurrences occur within 3 months of resection in Crohn's disease. There was a slight trend towards greater efficacy of Claversal; it could be worthwhile trying higher dosages and/or 5-ASA compounds with different intestinal release profiles.", "Recurrence of lesions of Crohn's disease of the ileum within 1 year after so-called curative resection was well documented by endoscopy in 73%-93% of cases. This study investigated the efficacy of mesalamine in reduction of endoscopic recurrence after surgery.\n In a double-blind, multicenter clinical trial, 87 patients were treated with 3 g/day mesalamine (Pentasa) or with placebo within 1 month after surgery. After 12 months of treatment, severity of endoscopic lesions was recorded with a five-point score; when it was not possible to reach the anastomosis by endoscopy, a barium enema was performed.\n Seventeen clinical relapses (seven in the mesalamine group) were recorded. After 12 months, the endoscopic lesions were less frequent and less severe in the mesalamine group than were those in the placebo group (chi 2, 13.5; P < 0.008). The overall rate of severe recurrence (score of 3-4 on endoscopy or radiological documentation) was 24% in the mesalamine group and 56% in the placebo group (chi 2, 8.57; P < 0.004; difference 32%; 95% confidence interval, 22-52). The odds ratio for active treatment was 4.1.\n This study shows that mesalamine is useful in decreasing the rate and severity of endoscopic recurrences after curative surgery for ileal Crohn's disease.", "Because the reoperation rate for Crohn's disease is high after resective surgery, use of conservative surgery has increased. Mesalamine was investigated for the prevention of postoperative relapse, with disappointing results. The role of azathioprine in the postoperative setting is unknown. We aimed to compare the efficacy and safety of azathioprine and mesalamine in the prevention of clinical and surgical relapse in patients who have undergone conservative surgery for Crohn's disease.\n In a prospective, open-label, randomized study, 142 patients received azathioprine (2 mg. kg -1. day -1 ) or mesalamine (3 g/day) for 24 months. Clinical relapse was defined as the presence of symptoms with a Crohn's Disease Activity Index score >200 and surgical relapse as the presence of symptoms refractory to medical treatment or complications requiring surgery.\n After 24 months, the risk of clinical relapse was comparable in the azathioprine and mesalamine groups, both on intention-to-treat (odds ratio [OR], 2.04; 95% confidence interval [CI], 0.89-4.67) and per-protocol analyses (OR, 1.79; 95% CI, 0.80-3.97). No difference was observed with respect to surgical relapse at 24 months between the 2 groups. In a subgroup analysis, azathioprine was more effective than mesalamine in preventing clinical relapse in patients with previous intestinal resections (OR, 4.83; 95% CI, 1.47-15.8). More patients receiving azathioprine withdrew from treatment due to adverse events than those receiving mesalamine (22% vs. 8%; P = 0.04).\n While no difference was observed in the efficacy of azathioprine and mesalamine in preventing clinical and surgical relapses after conservative surgery, azathioprine is more effective in those patients who have undergone previous intestinal resection.", "Crohn's disease commonly recurs after intestinal resection. We evaluated whether the administration of infliximab after resective intestinal surgery for Crohn's disease reduces postoperative recurrence.\n We randomly assigned 24 patients with Crohn's disease who had undergone ileocolonic resection to receive intravenous infliximab (5 mg/kg), administered within 4 weeks of surgery and continued for 1 year, or placebo. The primary end point was the proportion of patients with endoscopic recurrence at 1 year. Secondary end points were clinical recurrence and remission and histologic recurrence.\n The rate of endoscopic recurrence at 1 year was significantly lower in the infliximab group (1 of 11 patients; 9.1%) compared with the placebo group (11 of 13 patients; 84.6%) (P = .0006). There was a nonsignificant higher proportion of patients in clinical remission in the infliximab group (8 of 10; 80.0%) compared with the placebo group (7 of 13; 53.8%) (P = .38). The histologic recurrence rate at 1 year was significantly lower in the infliximab group (3 of 11 patients; 27.3%) compared with the placebo group (11 of 13 patients; 84.6%) (P = .01). The occurrence of adverse events was similar between the placebo and infliximab groups, and none occurred in the immediate postoperative period.\n Administration of infliximab after intestinal resective surgery was effective at preventing endoscopic and histologic recurrence of Crohn's disease.", "The role of mesalazine in preventing the clinical recurrence of Crohn's disease after surgery has been shown in a meta-analysis of all published studies. No clear relationship, however, has been shown between dosage and response.\n To evaluate whether 4.0 g/day of mesalazine may offer therapeutic advantages over 2.4 g/day in the prevention of both endoscopic and clinical post-operative recurrence of Crohn's disease.\n The study was a double-blind, randomized, multi-centre, prospective, controlled clinical trial. Two hundred and six patients, submitted to first or second intestinal resection for Crohn's disease limited to the terminal ileum, with or without involvement of the caecum/ascending colon, were enrolled. Of these, 101 were randomly allocated to receive 4.0 g/day of mesalazine (Asacol, Giuliani SpA, Milan, Italy) and 105 to receive 2.4 g/day, starting 2 weeks after surgery. The primary outcome was endoscopic recurrence, at 12 months after surgery. Three different degrees of endoscopic recurrence were evaluated (endoscopic scores: > 0, > 1 and > 2). The secondary outcome was clinical recurrence, defined as a Crohn's disease activity index of more than 150 points or an increase in the Crohn's disease activity index of 100 points or more. For statistical analysis, chi-square, Wilcoxon and Cox regression model tests were used, when appropriate.\n Eighty-four patients in the 4.0 g/day group and 81 patients in the 2.4 g/day group were evaluable by endoscopy. Endoscopic recurrence of > 0 was significantly higher in the 2.4 g/day group than in the 4.0 g/day group (62% vs. 46%; P < 0.04). No difference was observed between the two groups with regard to the other two endoscopic outcomes (> 1 and > 2) or clinical recurrence.\n A 4.0 g/day regimen of mesalazine does not offer a clinically significant advantage over a 2.4 g/day regimen in the prevention of post-operative endoscopic and clinical recurrence of Crohn's disease at 1 year of follow-up.", "No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn's disease. The aim of the current trial was to compare 6-mercaptopurine (6-MP) and mesalamine with placebo for the prevention of clinical, endoscopic, and radiographic recurrence of Crohn's disease after resection and ileocolic anastomosis.\n Five centers randomized 131 patients to receive 6-MP (50 mg), mesalamine (3 g), or placebo daily in a double-blind, double-dummy trial. Patients had clinical assessments at 7 weeks and then every 3 months; colonoscopy at 6, 12, and 24 months; and small bowel series at 12 and 24 months. End points were clinical, endoscopic, and radiographic recurrence rates at 24 months.\n Clinical recurrence rates (intent to treat) by life-table analysis at 24 months were 50% (95% confidence interval [CI], 34%-68%), 58% (95% CI, 41%-75%), and 77% (95% CI, 61%-91%) in patients receiving 6-MP, mesalamine, and placebo, respectively. Endoscopic recurrence rates were 43% (95% CI, 28%-63%), 63% (95% CI, 47%-79%), and 64% (95% CI, 46%-81%), and radiographic recurrence rates were 33% (95% CI, 19%-54%), 46% (95% CI, 29%-66%), and 49% (95% CI, 30%-72%), respectively. 6-MP was more effective than placebo ( P < 0.05) at preventing clinical and endoscopic recurrence over 2 years. Patient withdrawals resulted in 69% of the study population evaluable for the clinical recurrence end point.\n 6-MP, 50 mg daily, was more effective than placebo at preventing postoperative recurrence of Crohn's disease and should be considered as a maintenance therapy after ileocolic resection.", "Complications of Crohn's disease (CD) lead to surgery in about 70-90% of patients. The majority of patients suffer from relapse of the disease. Colonic bacteria are essential to the development of CD. Therefore, a rationale exists in trying to prevent relapse by manipulation of gut microflora. This is feasible by treatment with probiotics or antibiotics. Synbiotic 2000 is a cocktail containing 4 probiotic species and 4 prebiotics. It is rational to pursue that it could be effective in preventing postoperative disease. We sought to check weather treatment with Synbiotic 2000 could prevent postoperative recurrence in patients with CD. This was a prospective multicenter, randomized study. Patients were randomized to active treatment or placebo in a 2:1 ratio. Follow-up consisted of endoscopic, clinical, and laboratory parameters. Thirty patients were enrolled. No differences were found between the 2 treatment groups regarding gender, age at diagnosis, age at surgery, weight, smoking status, type of disease, length of the resected segment, or medical treatment prior to surgery. No difference in either endoscopic or clinical relapse rate was found between patients treated with once daily dose of Synbiotic 2000 or placebo. In our small study, Synbiotic 2000 had no effect on postoperative recurrence of patients with CD. Larger studies in patients with the inflammatory type of CD undergoing surgery, using higher doses of probiotics cocktail might prove effective.", "Seventy percent of Crohn's disease (CD) patients exhibit anastomotic recurrence within 1 year after ileo-caecal surgery. Recent clinical trials suggest the beneficial use of probiotics in the control of intestinal inflammation in pouchitis and ulcerative colitis. This study is a multicenter clinical trial evaluating the efficacy of an oral administration of the probiotic LAl on early post-operative endoscopic recurrence of CD.\n Seventy patients with CD were enrolled prior to elective ileo-caecal resection and randomly assigned after surgery to daily treatment with either Lactobacillus johnsonii, LA1, Nestle (1010 colony-forming units, CFU) (group A, n = 34) or placebo (group B, n = 36) for 12 weeks. The primary objective was to assess the effect of LAl on the endoscopic recurrence rate at 12 weeks. Stratification was performed according to smoking status at randomization.\n Seven and 14 patients were excluded in the LA1 and placebo groups, respectively. In intention-to-treat analysis, the mean endoscopic score was not significantly different between the two treatment groups at 3 months (LA1 versus placebo: 1.50 +/- 1.32 versus 1.22+/-1.37, treatment effect: P = 0.48, smoke effect: P = 0.72). The percentage of patients with severe recurrence (i3 + i4) was 21% and 15% in the LAl and placebo groups, respectively (P = 0.33). Using a per-protocol (PP) analysis, the mean endoscopic score was not significantly different between the two treatment groups (LAl versus placebo groups: 1.44 +/-1.31 versus 1.05 +/- 1.21, P = 0.32). The percentage of patients with severe recurrence (i3 + i4) was 19% and 9% in the LAl and placebo groups, respectively (P = 0.054). Clinical relapse rate (CDAI [CD activity index] > 150, with an increase of CDAI > 70 points or greater from baseline) in the LAl and placebo groups was 15% (4/27) and 13.5% (3/22), respectively (PP analysis: chi-square test, P = 0.91 and log-rank test: P = 0.79).\n Oral administration of the probiotic LA1 in patients with CD failed to prevent early endoscopic recurrence at 12 weeks after ileo-caecal resection.", "New lesions of Crohn's disease occur early after ileal or ileocolonic resection and ileocolonic anastomosis. We performed a double blind controlled trial to evaluate the safety and tolerance of recombinant human interleukin 10 (IL-10; Tenovil) in subjects operated on for Crohn's disease. We also assessed the effect of Tenovil in preventing endoscopic recurrence 12 weeks after surgery.\n Patients with Crohn's disease who underwent curative ileal or ileocolonic resection and primary anastomosis were randomised within two weeks after surgery to receive subcutaneous Tenovil 4 microg/kg once daily (QD) (n=22) or 8 microg/kg twice weekly (TIW) (n=21), or placebo (QD or TIW) (n=22). An ileocolonoscopy was performed after 12 weeks of treatment.\n Compliance was excellent. The most frequently observed adverse events were mild and moderate in severity and equally distributed across treatment groups. Thirty seven patients in the pooled Tenovil group and 21 patients in the pooled placebo group were evaluable by endoscopy. At 12 weeks, 11 of 21 patients (52%) in the placebo group had recurrent lesions compared with 17 of 37 patients (46%) in the Tenovil group (ns). The incidence of severe endoscopic recurrence was similar in both groups (9%).\n Tenovil treatment for 12 consecutive weeks in patients with Crohn's disease after intestinal resection was safe and well tolerated. No evidence of prevention of endoscopic recurrence of Crohn's disease by Tenovil was observed.", "More than 80% of Crohn's disease (CD) patients undergoing resection suffer recurrence of their disease. Therapy with aminosalicylates, antimetabolites, or antibiotics leads to a modest reduction in the incidence of recurrence. Goal: We sought to examine whether metronidazole for 3 months together with azathioprine (AZA) for 12 months is superior to metronidazole alone to reduce recurrence of postoperative CD in \"high-risk\" patients.\n CD patients undergoing curative ileocecal resection with >or=1 risk factor for recurrence received metronidazole (3 months) and AZA/placebo (12 months). The primary end point was the proportion of patients with significant endoscopic recurrence 3 and 12 months after surgery. Secondary end points included clinical recurrence, safety, and tolerability of treatment.\n Eighty-one patients were randomized; 19 discontinued the study early. Significant endoscopic recurrence was observed in 14 of 32 (43.7%) patients in the AZA group and in 20 of 29 (69.0%) patients in the placebo group at 12 months postsurgery (P = .048). Intention-to-treat analysis revealed endoscopic recurrence in 22 of 40 (55%) in the AZA group and 32 of 41 (78%) in the placebo group at month 12 (P = .035). At month 12, 7 of 32 patients had no endoscopic lesions in the AZA group, versus 1 of 29 in the placebo group (P = .037).\n Despite the enhanced risk of recurrence, the overall incidence of significant recurrence was rather low, probably owing to the metronidazole treatment that all patients received. Concomitant AZA resulted in lower endoscopic recurrence rates and less severe recurrences 12 months postsurgery, predicting a more favorable clinical outcome. This combined treatment seems to be recommendable to all operated CD patients with an enhanced risk for recurrence.", "Experimental studies have shown that luminal bacteria may be involved in Crohn's disease. Probiotics are a possible alternative to antibiotics. The aim of this randomised placebo controlled study was to determine if Lactobacillus GG, given by mouth for one year, could prevent Crohn's recurrent lesions after surgery or to reduce their severity.\n Patients operated on for Crohn's disease in whom all of the diseased gut had been removed were randomly allocated to receive 12 billion colony forming units of Lactobacillus or identical placebo for one year. Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms. Endoscopic recurrence was defined as grade 2 or higher of Rutgeerts scoring system.\n Eight of 45 patients were excluded from the trial (three for non-compliance and five for protocol violations). Clinical recurrence was ascertained in three (16.6%) patients who received Lactobacillus and in two (10.5%) who received placebo. Nine of 15 patients in clinical remission on Lactobacillus (60%) had endoscopic recurrence compared with six of 17 (35.3%) on placebo (p=0.297). There were no significant differences in the severity of the lesions between the two groups.\n Lactobacillus GG seems neither to prevent endoscopic recurrence at one year nor reduce the severity of recurrent lesions.", "Recurrence rate is high after operation for Crohn's disease. A multicenter trial was performed to study the effect of radical or nonradical operation and of sulfasalazine prophylaxis versus placebo on postoperative recurrence rate in 232 patients with Crohn's disease. Sixteen medical and surgical centers participated in the study, 7 operating radically and 9 nonradically. The follow-up period lasted 3 years, the allocation to drug treatment was randomized and double blind. Recurrence was significantly less frequent and occurred later in patients who were operated nonradically. Patients on sulfasalazine prophylaxis had a better prognosis than on placebo. This effect was statistically significant in the first 2 years of treatment. Both strategies were additive: nonradical operation and sulfasalazine had the best prognosis, radical operation and placebo was worst. It is concluded that postoperative recurrence is best prevented by resecting nonradically and prescribing 3 g of sulfasalazine daily at least over 2 years." ]

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[ "Effects on parental mental health of an education and skills training program for parents of young children with autism: a randomized controlled trial.", "Treatment of children with autism: a randomized controlled trial to evaluate a caregiver-based intervention program in community day-care centers.", "A randomized, controlled trial of a home-based intervention program for children with autism and developmental delay.", "Parent-mediated communication-focused treatment in children with autism (PACT): a randomised controlled trial.", "A new social communication intervention for children with autism: pilot randomised controlled treatment study suggesting effectiveness.", "Learning through interaction in children with autism: preliminary data from asocial-communication-based intervention.", "A pilot randomised control trial of a parent training intervention for pre-school children with autism. Preliminary findings and methodological challenges.", "Qigong massage treatment for sensory and self-regulation problems in young children with autism: a randomized controlled trial.", "Randomized trial of intensive early intervention for children with pervasive developmental disorder.", "A pilot randomized controlled trial of DIR/Floortime™ parent training intervention for pre-school children with autistic spectrum disorders.", "A parent-mediated intervention to increase responsive parental behaviors and child communication in children with ASD: a randomized clinical trial.", "Randomized controlled trial for early intervention for autism: a pilot study of the Autism 1-2-3 Project.", "Randomized controlled caregiver mediated joint engagement intervention for toddlers with autism.", "A randomized controlled trial of Hanen's 'More Than Words' in toddlers with early autism symptoms." ]

[ "To determine the impact of a parent education and behavior management intervention (PEBM) on the mental health and adjustment of parents with preschool children with autism.\n A randomized, group-comparison design involving a parent education and counseling intervention to control for nonspecific therapist effects and a control sample was used. Two metropolitan and two rural regions were randomly allocated to intervention groups (n = 70) or control (n = 35). The parents of consecutive children with autism (2(1/2)-5 years old) from the autism assessment services for the intervention regions were then randomly allocated to either a 20-week manual-based parent education and behavior management intervention (n = 35) or a manual-based parent education and counseling intervention (n = 35). The main outcome measure of parental mental health was the General Health Questionnaire used pre- and postintervention and at 6-month follow-up.\n Both treatments resulted in significant and progressive improvement in overall mental health at follow-up (F = 2, 97, p =.007) and mental health significantly improved over time in the 54% of principal caregivers who had the highest levels of mental health problems. The parent education and behavior management intervention was effective in alleviating a greater percentage of anxiety, insomnia, and somatic symptoms and family dysfunction than parent education and counseling at 6-month follow-up.\n A 20-week parent education and skills training program for parents of young children newly diagnosed with autism provides significant improvements in parental mental health and adjustment, justifying its addition to early intervention programs at least for parents with mental health problems.", "This study reports on the results of a randomized controlled trial that evaluated a caregiver-based intervention program for children with autism in community day-care centers. Thirty-five preschool children with a DSM III-R diagnosis of autism or pervasive developmental disorder were randomized to an experimental or control group. Children in the experimental group were enrolled in day care and their parents and child care workers received a 12-week intervention consisting of lectures and on-site consultations to day-care centers. In addition, supportive work was undertaken with families. Control subjects received day care alone. In the experimental group, there were greater gains in language abilities, significant increases in caregivers' knowledge about autism, greater perception of control on the part of mothers, and greater parent satisfaction. We conclude that this research design demonstrated that the intervention was significantly superior to day care alone.", "This study aimed to (1) investigate whether provision of a home-based program in addition to a center-based program improves development in young children with disabilities and coping abilities of their families and (2) describe the characteristics of children and families who benefit most from the intervention.\n Fifty-nine children, aged 3-5 years, with no cerebral palsy, participated in the study. Half of the group was randomized to receive an additional program in their homes. A special education teacher provided 40 visits over 12 months working with the families to help generalize skills to the home environment and assist with their concerns. All children were assessed before and after the intervention, and families completed questionnaires assessing family stress, support, and empowerment on both occasions. Differences in change over time and between the intervention and control group were analyzed by repeated measures and the association between characteristics of children and families with improved outcome by multivariate analysis of variance.\n Change in cognitive development and behavior (in the centers) over time favored the children who received the extra intervention (p = .007 and p = .007, respectively). The groups did not differ on any of the family measures of change. Multivariate analysis of variance revealed more improvement for children in the intervention group from higher than lower stressed families.\n Results suggest the need for daily reinforcement of skills learned at the center-based program and the importance of involving families, especially those with few resources and relatively high stress.", "Results of small trials suggest that early interventions for social communication are effective for the treatment of autism in children. We therefore investigated the efficacy of such an intervention in a larger trial.\n Children with core autism (aged 2 years to 4 years and 11 months) were randomly assigned in a one-to-one ratio to a parent-mediated communication-focused (Preschool Autism Communication Trial [PACT]) intervention or treatment as usual at three specialist centres in the UK. Those assigned to PACT were also given treatment as usual. Randomisation was by use of minimisation of probability in the marginal distribution of treatment centre, age (</=42 months or >42 months), and autism severity (Autism Diagnostic Observation Schedule-Generic [ADOS-G] algorithm score 12-17 or 18-24). Primary outcome was severity of autism symptoms (a total score of social communication algorithm items from ADOS-G, higher score indicating greater severity) at 13 months. Complementary secondary outcomes were measures of parent-child interaction, child language, and adaptive functioning in school. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN58133827.\n 152 children were recruited. 77 were assigned to PACT (London [n=26], Manchester [n=26], and Newcastle [n=25]); and 75 to treatment as usual (London [n=26], Manchester [n=26], and Newcastle [n=23]). At the 13-month endpoint, the severity of symptoms was reduced by 3.9 points (SD 4.7) on the ADOS-G algorithm in the group assigned to PACT, and 2.9 (3.9) in the group assigned to treatment as usual, representing a between-group effect size of -0.24 (95% CI -0.59 to 0.11), after adjustment for centre, sex, socioeconomic status, age, and verbal and non-verbal abilities. Treatment effect was positive for parental synchronous response to child (1.22, 0.85 to 1.59), child initiations with parent (0.41, 0.08 to 0.74), and for parent-child shared attention (0.33, -0.02 to 0.68). Effects on directly assessed language and adaptive functioning in school were small.\n On the basis of our findings, we cannot recommend the addition of the PACT intervention to treatment as usual for the reduction of autism symptoms; however, a clear benefit was noted for parent-child dyadic social communication.\n UK Medical Research Council, and UK Department for Children, Schools and Families.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness. Randomised controlled trial (RCT) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder. We aimed to test a new theoretically based social communication intervention targeting parental communication in a randomised design against routine care alone.\n The intervention was given in addition to existing care and involved regular monthly therapist contact for 6 months with a further 6 months of 2-monthly consolidation sessions. It aimed to educate parents and train them in adapted communication tailored to their child's individual competencies. Twenty-eight children with autism were randomised between this treatment and routine care alone, stratified for age and baseline severity. Outcome was measured at 12 months from commencement of intervention, using standardised instruments.\n All cases studied met full Autism Diagnostic Interview (ADI) criteria for classical autism. Treatment and controls had similar routine care during the study period and there were no study dropouts after treatment had started. The active treatment group showed significant improvement compared with controls on the primary outcome measure--Autism Diagnostic Observation Schedule (ADOS) total score, particularly in reciprocal social interaction--and on secondary measures of expressive language, communicative initiation and parent-child interaction. Suggestive but non-significant results were found in Vineland Adaptive Behaviour Scales (Communication Sub-domain) and ADOS stereotyped and restricted behaviour domain.\n A Randomised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients. This pilot study suggests significant additional treatment benefits following a targeted (but relatively non-intensive) dyadic social communication treatment, when compared with routine care. The study needs replication on larger and independent samples. It should encourage further RCT designs in this area.", "The study evaluates a social-communication-based approach to autism intervention aimed at improving the social interaction skills of children with autism spectrum disorder. We report preliminary results from an ongoing randomized controlled trial of 51 children aged 2 years 0 months to 4 years 11 months. Participants were assigned to either a target treatment or community treatment group. Families in the target treatment group were given 2 hours of therapy and coaching each week in an intervention emphasizing social-interaction and the parent-child relationship. Children in the community treatment group received a variety of services averaging 3.9 hours per week. After 12 months, outcomes were measured to determine changes in the groups in social interaction and communication. In addition, a regression analysis was conducted to determine whether changes in social interaction skills were associated with language development. Results suggest that children in the treatment group made significantly greater gains in social interaction skills in comparison to the community treatment group, but no between-group differences were found for standard language assessments. Initiation of joint attention, involvement, and severity of language delay were found to be significantly associated with improvement of language skills in children with autism. Finally caregiver skills targeted by the intervention were found to be significantly associated with changes in children's interaction skills.", "Few attempts have been made to conduct randomised control trials (RCTs) of interventions for pre-school children with autism. We report findings of a pilot RCT for a parent training intervention with a focus on the development of joint attention skills and joint action routines. Twenty-four children meeting ICD-10 criteria for childhood autism (mean age = 23 months) were identified using the CHAT screen and randomised to the parent training group or to local services only. A follow-up was conducted 12 months later (mean age = 35 months). There was some evidence that the parent training group made more progress in language development than the local services group. However, the present pilot study was compromised by several factors: a reliance on parental report to measure language, non-matching of the groups on initial IQ, and a lack of systematic checking regarding the implementation of the parent training intervention. Furthermore, three parents in the local services group commenced intensive, home-based behavioural intervention during the course of the study. The difficulties encountered in the conduct of RCTs for pre-school children with autism are discussed. Methodological challenges and strategies for future well-designed RCTs for autism interventions are highlighted.", "Autism is commonly associated with sensory and self-regulatory disturbances. This article presents a randomized controlled study evaluating the effect of a 5-month intervention directed toward improving sensory impairment, digestion, and sleep in 46 children with autism < age 6. The intervention, Qigong Sensory Training (QST), is a qigong massage intervention based in Chinese medicine. It is two-pronged: Trainers work with children directly 20 times over 5 months, and parents give the massage daily to their children. Improvement was evaluated in two settings--preschool and home--by teachers (blind to group) and parents. Teacher evaluations showed that treated children had significant classroom improvement of social and language skills and reduction in autistic behavior compared with wait-list control participants. These findings were confirmed by parent data, indicating that the gains had generalized across contexts. A model and supporting data for understanding and treating sensory and self-regulation problems in autism is presented.", "Young children with pervasive developmental disorder were randomly assigned to intensive treatment or parent training. The intensive treatment group (7 with autism, 8 with pervasive developmental disorder not otherwise specified--NOS) averaged 24.52 hours per week of individual treatment for one year, gradually reducing hours over the next 1 to 2 years. The parent training group (7 with autism, 6 with pervasive developmental disorder NOS) received 3 to 9 months of parent training. The groups appeared similar at intake on all measures; however, at follow-up the intensive treatment group outperformed the parent training group on measures of intelligence, visual-spatial skills, language, and academics, though not adaptive functioning or behavior problems. Children with pervasive developmental disorder NOS may have gained more than those with autism.", "This pilot study was designed to test the efficacy of adding home-based Developmental, Individual-Difference, Relationship-Based (DIR)/Floortime™ intervention to the routine care of preschool children with autistic spectrum disorder. Measures of functional emotional development and symptom severity were taken. It was found that after the parents added home-based DIR/Floortime™ intervention at an average of 15.2 hours/week for three months, the intervention group made significantly greater gains in all three measures employed in the study: Functional Emotional Assessment Scale (FEAS) (F = 5.1, p = .031), Childhood Autism Rating Scale (F = 2.1, p = .002), and the Functional Emotional Questionnaires (F = 6.8, p = .006). This study confirms the positive results obtained by a previous DIR pilot study (Solomon et al., 2007).", "Longitudinal research has demonstrated that responsive parental behaviors reliably predict subsequent language gains in children with autism spectrum disorder. To investigate the underlying causal mechanisms, we conducted a randomized clinical trial of an experimental intervention (Focused Playtime Intervention, FPI) that aims to enhance responsive parental communication (N = 70). Results showed a significant treatment effect of FPI on responsive parental behaviors. Findings also revealed a conditional effect of FPI on children's expressive language outcomes at 12-month follow up, suggesting that children with baseline language skills below 12 months (n = 24) are most likely to benefit from FPI. Parents of children with more advanced language skills may require intervention strategies that go beyond FPI's focus on responsive communication.", "We piloted a 2-week \"Autism-1-2-3\" early intervention for children with autism and their parents immediately after diagnosis that targeted at (1) eye contact, (2) gesture and (3) vocalization/words. Seventeen children were randomized into the Intervention (n = 9) and Control (n = 8) groups. Outcome measures included the Autism Diagnostic Observation Schedule, Ritvo-Freeman Real Life Rating Scale, Symbolic Play Test, and Parenting Stress Index. Children with autism improved in language/communication, reciprocal social interaction, and symbolic play. Parents perceived significant improvement in their children's language, social interaction, and their own stress level. This intervention can serve as short-term training on communication and social interaction for children with autism, and reduce the stress of their parents during the long waiting time for public health services.", "This study aimed to determine if a joint attention intervention would result in greater joint engagement between caregivers and toddlers with autism. The intervention consisted of 24 caregiver-mediated sessions with follow-up 1 year later. Compared to caregivers and toddlers randomized to the waitlist control group the immediate treatment (IT) group made significant improvements in targeted areas of joint engagement. The IT group demonstrated significant improvements with medium to large effect sizes in their responsiveness to joint attention and their diversity of functional play acts after the intervention with maintenance of these skills 1 year post-intervention. These are among the first randomized controlled data to suggest that short-term parent-mediated interventions can have important effects on core impairments in toddlers with autism. Clinical Trials #: NCT00065910.", "This randomized controlled trial compared Hanen's 'More than Words' (HMTW), a parent-implemented intervention, to a 'business as usual' control group.\n Sixty-two children (51 boys and 11 girls; M age = 20 months; SD = 2.6) who met criteria for autism spectrum disorders (ASD) and their parents participated in the study. The HMTW intervention was provided over 3.5 months. There were three measurement periods: prior to randomization (Time 1) and at 5 and 9 months post enrollment (Times 2 and 3). Children's communication and parental responsivity were measured at each time point. Children's object interest, a putative moderator, was measured at Time 1.\n There were no main effects of the HMTW intervention on either parental responsivity or children's communication. However, the effects on residualized gains in parental responsivity from Time 1 to both Times 2 and 3 yielded noteworthy effect sizes (Glass's Δ = .71, .50 respectively). In contrast, there were treatment effects on child communication gains to Time 3 that were moderated by children's Time 1 object interest. Children with lower levels of Time 1 object interest exhibited facilitated growth in communication; children with higher levels of object interest exhibited growth attenuation.\n The HMTW intervention showed differential effects on child communication depending on a baseline child factor. HMTW facilitated communication in children with lower levels of Time 1 object interest. Parents of children who evidence higher object interest may require greater support to implement the HMTW strategies, or may require different strategies than those provided by the HMTW curriculum.\n © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health." ]

[ "9989566", "9545995", "8048341", "11041534" ]

[ "Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response.", "Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. The Risperidone Study Group.", "The tolerability and efficacy of the atypical neuroleptic remoxipride compared with clozapine and haloperidol in acute schizophrenia.", "Risperidone versus clozapine in treatment-resistant schizophrenia: a randomized pilot study." ]

[ "Clozapine and risperidone were the first two \"second-generation\" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents.\n After a baseline fluphenazine treatment period, 29 patients participated in a 6-week, double-blind, parallel-group comparison of the effects of these agents.\n Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone.\n The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed.", "The purpose of this study was to compare the short-term efficacy and safety of risperidone and clozapine in treatment-resistant chronic schizophrenic patients.\n In a controlled double-blind, multicenter study, 86 inpatients with chronic schizophrenia (DSM-III-R), who were resistant to or intolerant of conventional neuroleptics, were randomly assigned to receive risperidone or clozapine for 8 weeks after a 7-day washout period. After a 1-week dose-titration phase, doses were fixed at 6 mg/day of risperidone and 300 mg/day of clozapine for 1 week and then adjusted according to each patient's response. The final mean doses were 6.4 mg/day of risperidone and 291.2 mg/day of clozapine. Treatment efficacy and safety were evaluated with several well-known rating scales.\n Both risperidone and clozapine significantly reduced the severity of psychotic symptoms (scores on the Positive and Negative Syndrome Scale and the Clinical Global Impression scale) from baseline, with no significant between-group differences. At endpoint, 67% of the risperidone group and 65% of the clozapine group were clinically improved (reduction of 20% or more in total Positive and Negative Syndrome Scale score). Risperidone appeared to have a faster onset of action. In both groups extrapyramidal symptoms and other adverse events were few, and their severity was generally mild. Neither group showed evidence of a relation between drug plasma concentrations and clinical effectiveness.\n Risperidone was well tolerated and as effective as medium doses of clozapine in patients with chronic schizophrenia who had been resistant to or intolerant of conventional neuroleptics.", "Remoxipride and clozapine are new neuroleptics that are thought to be superior to the substances in use by their efficacy and tolerance. At the University Clinic of Psychiatry in Düsseldorf a double-blind study with 54 patients diagnosed as schizophrenic in accordance with DSM-III was conducted to record the influence of the neuroleptics remoxipride, clozapine and haloperidol on schizophrenic psychosis. The schizophrenic symptoms were rated by the AMDP-system (Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie), Brief Psychiatric Rating Scale and the Clinical Global Impression on days 0, 7, 14, 21 and 28 of treatment to evaluate the degree of change in psychopathology. The tolerance of the neuroleptic treatment was checked by the doctor's overall impression and the somatic findings of the AMDP-system. All 3 neuroleptics reduced the schizophrenic symptoms to a similar degree but showed differentiation as to their side effects.", "1. The atypical antipsychotic risperidone may constitute an alternative to clozapine, the current treatment of choice for refractory schizophrenia. The objectives of this study were to evaluate the effectiveness of risperidone in comparison to clozapine in everyday practice and to assess the feasibility of a pragmatic trial procedure. 2. Patients were randomly assigned to open-label clozapine or risperidone treatment for 10 weeks and treatment outcomes were assessed blindly. Twenty-one patients were recruited and nineteen entered the randomized phase. 3. Five of 10 participants allocated to clozapine and one of nine risperidone participants dropped out before study completion. Five clozapine patients and six risperidone patients achieved clinical improvement, defined as a 20% decrease in the Positive and Negative Symptom Scale (PANSS) total score. No significant differences between the groups were detected in baseline or endpoint positive or negative symptoms, disease severity, or global or social functioning scores. Patients' opinion on the drugs did not differ between groups. 4. The findings of the intention-to-treat analysis of this study corroborates previous findings that risperidone may be equally effective as clozapine, and supports the feasibility and need of a multicenter randomized pragmatic trial with sufficient power to detect differences between treatments." ]

[ "10445363", "2617141", "9046395", "6583062", "2133940", "9082855", "7709907", "2653850" ]

[ "Long-term follow-up of early treatment of unilateral forced posterior cross-bite. Orofacial status.", "Longitudinal study on the effect of early interceptive treatment in 4-year-old children with unilateral cross-bite.", "Comparison of Hyrax and bonded expansion appliances.", "The effect of early interceptive treatment in children with posterior cross-bite.", "Two-point rapid palatal expansion: an alternate approach to traditional treatment.", "Skeletal and dental changes after maxillary expansion in the mixed dentition.", "A clinical investigation of the correction of unilateral first molar crossbite with a transpalatal arch.", "Slow maxillary expansion: a comparison between banded and bonded appliances." ]

[ "Twenty-nine subjects, 20 years old on average and all treated at 4 years of age for unilateral forced posterior dento-alveolar cross-bite by grinding or by expansion of the upper dental arch, were clinically examined to evaluate the long-term effects of their treatment. The frequency of successful treatment-indicated as stable correction of the cross-bite-by means of only 1 treatment sequence was 59%; by grinding, 57%; and by expansion, 60%. The 18 subjects that had only been treated at the age of 4 years formed the 'early group' in our study. Eleven of our subjects had been retreated later in the mixed or permanent dentition because of a relapse of the unilateral forced posterior cross-bite and formed the 'late group'. A significantly higher frequency of mouth breathing, breathing obstacles, and snoring was found in this group. According to our clinical investigation, 2 of the subjects in our cohort still had a unilateral forced posterior cross-bite. Our findings regarding masticatory performance, bite force, and endurance showed no significant differences between the initial cross-bite and the healthy sides or between the early and the late group subjects, which showed that the masticatory function of the treated subjects was symmetrical. Grinding and expansion treatments seem to display similar success rates in the long-term regarding correction of unilateral posterior forced cross-bite.", "To evaluate the results of early interceptive grinding and also the possibility of self-correction of unilateral cross-bite, 76 4-yr-old children with this malocclusion were divided into one treated and one untreated group. In the treatment group 50% of the children exhibited a normal transverse occlusion evaluated in the mixed dentition, at the age of 9. In the untreated group only 17% showed a spontaneous correction of the cross-bite. Among the studied dental variables the \"max./mand. arch width difference\" especially in the canine region was found to be a valuable predictor indicating whether cross-bite can be successfully treated in preschoolchildren by selective grinding. The results of this study support early treatment of unilateral cross-bite and gives the criteria whereby successful treatment by selective grinding may be expected.", "The majority of rapid maxillary expansion studies have reported the use of appliances with metal bands attached to the posterior teeth. Tooth extrusion, dental tipping, and an increase in the vertical dimension are often encountered, which may not coincide with treatment objectives. Bonded appliances using interocclusal acrylic may control the vertical dimension and expand the maxillary halves in a more bodily and symmetrical fashion. The purpose of this clinical trial was to determine, by radiographic analysis, the differences between a conventional banded expander (Hyrax) and a bonded acrylic expander. Fourteen patients who exhibited a need for expansion were enrolled in the study. The results suggest that the increase in the vertical dimension often seen with the more conventional Hyrax appliance may be minimized or negated with the bonded appliance. However, there appeared to be no significant difference between the amount of dental tipping or symmetrical expansion between the two appliances, as previously theorized.", "nan", "Rapid palatal expansion (RPE) causes separation of the lateral halves of the palate and traditionally has used four maxillary teeth as anchorage. The purpose of this study was to introduce a rapid palatal expander that requires only two anchor teeth (two-point RPEe) and to compare the expansion obtained with that from a Hyrax appliance. This study involved two groups of 25 children aged 7 to 15 years who were treated in a private orthodontist's office with either a Hyrax appliance or a two-point RPEe. Dental casts and occlusal radiographs were made before treatment and at least three months after stabilization of the appliance. Paired t-tests were performed to identify significant intragroup changes, and independent t-tests were performed to determine intergroup differences. The findings showed the two-point RPEe was as efficient as the Hyrax in obtaining dental expansion of the maxillary posterior teeth with less effect on the maxillary anterior and mandibular teeth. Therefore, the two-point RPEe may be useful in certain clinical situations.", "The purpose of this study was to compare skeletal and dental aspects of three different expansion methods in the mixed dentition period in sagittal, vertical, and transversal planes, treatment periods, complications, and relapse tendencies in early periods. Patients with unilateral or bilateral posterior crossbites in the mixed dentition were studied. They were divided into three groups of 10 patients in each group. The first group received treatment with removable plates for semirapid maxillary expansion; the second group with quad-helix appliances for slow maxillary expansion; and the third group with conventional fixed hyrax appliances for rapid maxillary expansion (RME). Lateral and posteroanterior cephalometric films, occlusal films, and dental casts were taken before and after expansion, and after retention with the same appliances. Cephalometric and dental cast analyses were made. Both skeletal and dental changes were observed after all three expansion methods.", "The correction of a unilateral first molar crossbite with a Goshgarian type of transpalatal arch was evaluated in 35 children from 6 years, 8 months to 15 years, 11 months old. Fifteen of the children were treated with an arch activated for expansion only and 20 children with an arch activated in a similar way but with the inclusion of buccal root torque of the anchorage tooth. With both types of activation, the arches worked in a statically determinate system, i.e., the tooth in crossbite was allowed to tip buccally. The movements of the first molars as a result of the treatment were monitored by measurements on dental casts and frontal cephalometric roentgenograms. In addition, the width of the midpalatal suture was measured on occlusal roentgenograms of the maxilla. In the children treated with an arch activated only for expansion, the molars on both sides of the dental arch moved buccally during the treatment. In the children treated by torque activation, on the other hand, there was a considerable buccal movement of the molar on the side of the crossbite without any significant buccal movement of the anchorage tooth. In individual cases, the molar on the noncrossbite side moved and tipped palatally and in some cases buccally but to a minor degree. With both types of activation, there was only a slight change in inclination of the transverse occlusal plane through the first molars; the plane opened up slightly toward the side of the crossbite. For both types of activation, there was a slight widening of the palatal suture during the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)", "Various investigations have mentioned the use of a bonded maxillary expansion appliance. It was postulated that a full coverage of the occlusal surfaces by acrylic would remove interferences during the lateral displacement of the two maxillary bones and would lessen the resistance to maxillary expansion. The first objective of this study was to compare two appliances, a bonded and a banded Minne expander using a continuous force of two pounds, which would produce a slow maxillary expansion. The second objective was to evaluate the ratio between the skeletal and dental response to slow maxillary expansion, and to compare these results to those obtained with a rapid maxillary expansion procedure. Each experimental group consisted of 5 patients, aged between 8 and 12 years wearing the two different appliances. Prior to treatment they were implanted according to the Björk technique. The slow expansion period lasted 7 to 15 weeks followed by a retention period of 12 weeks. Post-retention observations followed 12 weeks after the end of retention. No significant difference was found between banded and bonded appliances in regard to dental and skeletal expansion and relapse. The amount of skeletal versus dental movements equalled results obtained with rapid maxillary expansion. The relapse tendency appeared lower than with rapid maxillary expansion." ]

[ "3349967", "1628583", "12027917", "11080603", "6434595", "2303015", "4006888", "18343200", "2406126", "19010447", "3912787", "17201719", "17049927", "3516668", "3545797", "17904909" ]

[ "Neuropsychological assessment of subjects with uncontrolled epilepsy: effects of EEG feedback training.", "Controlled examination of effects of progressive relaxation training on seizure reduction.", "The efficacy of an educational treatment program for patients with epilepsy (MOSES): results of a controlled, randomized study. Modular Service Package Epilepsy.", "Psycho-educational therapy among Nigerian adult patients with epilepsy: a controlled outcome study.", "Cognitive-behavioral treatment of depressed affect among epileptics: preliminary findings.", "Sepulveda Epilepsy Education: the efficacy of a psychoeducational treatment program in treating medical and psychosocial aspects of epilepsy.", "Effects of a broad-spectrum behavior modification treatment program on children with refractory epileptic seizures.", "Acceptance and Commitment Therapy and yoga for drug-refractory epilepsy: a randomized controlled trial.", "Randomized trial of a program to enhance the competencies of children with epilepsy.", "A telephone-based self-management program for people with epilepsy.", "Effects of progressive relaxation on epilepsy: analysis of a series of cases.", "Evaluation of acceptance and commitment therapy for drug refractory epilepsy: a randomized controlled trial in South Africa--a pilot study.", "Preventing depression in adolescents with epilepsy.", "Cognitive-behavior therapy with adult patients with epilepsy: a controlled outcome study.", "Effects of a contingent relaxation treatment program on adults with refractory epileptic seizures.", "A psychosocial self-management program for epilepsy: a randomized pilot study in adults." ]

[ "A battery of neuropsychological tests was administered at baseline, postcontrol period, and posttraining period to 24 drug-refractory subjects with epilepsy participating in a study of sensorimotor electroencephalographic (EEG) normalization feedback training. Results revealed the following. First, subjects exhibited significant baseline deficits in psychosocial, cognitive and motor functioning. Second, certain tests discriminated subjects before training who were subsequently above and below the median in seizure reduction following EEG training. Subjects who showed the greatest seizure reduction performed better on a test of general problem-solving ability but not on other cognitive tests and worse on tests involving strong motor components and were more intact psychosocially. These subjects also took significantly fewer medications in combination than did less successful subjects. Third, improvement on several measures occurred following participation in the study. Cognitive and motor functioning improved only in subjects with the greatest seizure reduction and only after actual training as opposed to control conditions. Psychological functioning, as measured by the Minnesota Multiphasic Personality Inventory (MMPI) improved in both outcome groups. MMPI improvement, unlike cognitive improvement, was as likely to occur after control conditions, when seizure reduction had not yet occurred, as after EEG training. Thus, MMPI changes apparently reflected the nonspecific benefits of participation in this study.", "We determined the efficacy of progressive muscle relaxation in reducing seizure frequency. Subjects were 24 people with epilepsy attending an urban neurology clinic. The experimental design consisted of an 8-week baseline period, a treatment period of six sessions of progressive relaxation training (PRT, n = 13) or quiet sitting (QS, n = 11) and an 8-week follow up. In the PRT group, 11 subjects reported a decrease in seizure frequency (p less than 0.01), and in the QS group, 7 reported a decrease (p greater than 0.05). The mean decrease in seizure frequency was 29% for the PRT group (p less than 0.01) but only 3% for the QS group (p greater than 0.05). This is the fifth recent report of a controlled study documenting the success of progressive relaxation therapy in seizure reduction. PRT is inexpensive and noninvasive and facilitates patient participation. Such a technique should be incorporated into clinical practice.", "To evaluate the efficacy of the educational program MOSES (Modular Service Package Epilepsy). It was developed to improve patients' knowledge and understanding about their epilepsy, its treatment, and psychosocial consequences. The program intends to improve patients' coping with the disease, to strengthen self-esteem, and to support patients to become experts in managing their epilepsy.\n A controlled, randomized study design was used to examine the efficacy of MOSES. Patients from 22 epilepsy centers in Germany, Austria, and Switzerland were randomly allocated to either MOSES group (treatment group) or waiting-list group (control group). The 242 patients were aged from 16 to 80 years. The MOSES group (n = 113) completed the questionnaires immediately before the educational course (T1) and 6 months later (T2), and the control group (n = 129), 6 months before (T1) and immediately before (T2) the course. The questionnaires included generic instruments (SF-36, Rosenberg self-esteem Scale, von Zerssen Depression Scale), and epilepsy-specific scales (Restrictions in Daily Life, Epilepsy-Related Fears, Coping with Epilepsy and Adaptation). Depression was used as a moderator variable. Seizure frequency and satisfaction with therapy also were assessed. Multivariate analysis of variance (MANOVA) with repeated measurements and univariate analyses of variance were performed.\n The MANOVA showed that participants of the educational program improved significantly. Univariate analyses revealed improvements in knowledge (p < 0.001) and coping with epilepsy (p = 0.004), whereas important effects of MOSES on other epilepsy-specific measures and on generic questionnaires (SF-36, self-esteem) were not found. Participants of the MOSES program also improved in seizure outcome (p = 0.041) and became more satisfied with the therapy [better tolerability of antiepileptic drug (AED) therapy, fewer side effects; p = 0.014]. In addition, participants expressed being highly satisfied with the program.\n The study clearly indicates the need for patient education. Even patients with a long history of epilepsy and with additional handicaps or diseases benefitted from the MOSES program.", "Psychological interventions in relation to epilepsy are worthy of empirical investigation since there is broad agreement that the psycho-social problems of epilepsy are often more disabling than the seizure attacks. The present study using a controlled outcome design evaluated the efficacy of a 2-day psycho-educational program among patients with epilepsy in Nigeria. The psycho-educational program is the consequence of a two-stage study design, which set out to identify and evaluate psycho-social factors that determine interictal psychopathology in people with epilepsy. Thirty out-patients matched according to seizure type and frequency of seizures were randomly assigned to treatment (n = 15) or waiting-list control (n = 15) groups. The major outcome measures used were knowledge about illness schedule, the Becks depression inventory and the Crown-Crisp experiential index. Significant differences between the two groups were found on the three major scales used. The treatment group by within-group analyses, showed a substantial significant decrease in level of depression, a significant increase in the knowledge about epilepsy as well as a significant decrease in all measures of neurotic disorders except for hysterical sub-scale.", "Controlled study showed skills training for the management of depression in an epilepsy population to be effective. Cognitive-behavioral methods were utilized in a structured learning format with 13 clinically depressed epileptic \"students.\" Significantly greater reductions in dysphoria/depression as measured by the Depression Adjective Checklist and the Generalized Contentment Scale occurred among Ss in the treatment group than among control group Ss. Significant decreases in anger and anxiety/stress and increases in social activities were noted on the Community Adjustment Questionnaire (CAQ). Similar trends were evident on the Beck Depression Inventory and the CAQ depression scale.", "The present study evaluated the efficacy of the Sepulveda Epilepsy Education program (SEE), using a controlled outcome design. SEE is a 2-day psychoeducational treatment program designed to provide medical education and psychosocial therapy. Thirty-eight outpatients, matched according to seizure type and frequency, were randomly assigned to treatment (n = 20) or waiting-list control (n = 18) groups. The major outcome measures used were a 50-item true-false test specifically designed to evaluate the SEE program, the Washington Psychosocial Seizure Inventory, the Beck Depression Inventory, Lubin's Depression Adjective Checklist, the State-Trait Anxiety Inventory, the Acceptance of Disability Scale, and Sherer's Self-Efficacy Scale. Significant differences between the two groups were found on the three major subscales of the 50-item true-false test. The treatment group demonstrated a significant increase in overall understanding of epilepsy, a significant decrease in fear of seizures, and a significant decrease in hazardous medical self-management practices. In addition, an objective measure of blood levels of antiepileptic drugs (AEDs) showed the treatment group to have a significant increase in medication compliance.", "A group of 18 children with refractory epileptic seizures was divided into three groups--behavior modification treatment, attention control, and control groups--with the purpose of investigating the effects of a learning-based broad-spectrum treatment program superimposed on a regular medical treatment program. The design consisted of a 10-week baseline, 6-week intervention, and 10-week and 1-year follow-ups. A combination of number of seizures and seizure duration--termed \"seizure index\"--was used as a dependent measure. There was a significant reduction in seizure index only for those children receiving the behavior modification treatment, at both follow-ups. The results indicate that this behavioral treatment program may be of substantial help to children with epilepsy who are resistant to conventional drug therapy.", "There is a need for controlled outcome studies on behavioral treatment of epilepsy. The purpose of this study was to evaluate Acceptance and Commitment Therapy (ACT) and yoga in the treatment of epilepsy.\n The design consisted of a randomized controlled trial with repeated measures (N=18). All participants had an EEG-verified epilepsy diagnosis with drug-refractory seizures. Participants were randomized into one of two groups: ACT or yoga. Therapeutic effects were measured using seizure index (frequency x duration) and quality of life (Satisfaction with Life Scale, WHOQOL-BREF). The treatment protocols consisted of 12 hours of professional therapy distributed in two individual sessions, two group sessions during a 5-week period, and booster sessions at 6 and 12 months posttreatment. Seizure index was continuously assessed during the 3-month baseline and 12-month follow-up. Quality of life was measured after treatment and at the 6-month and 1-year follow-ups.\n The results indicate that both ACT and yoga significantly reduce seizure index and increase quality of life over time. ACT reduced seizure index significantly more as compared with yoga. Participants in both the ACT and yoga groups improved their quality of life significantly as measured by one of two quality-of-life instruments. The ACT group increased their quality of life significantly as compared with the yoga group as measured by the WHOQOL-BREF, and the yoga group increased their quality of life significantly as compared with the ACT group as measured by the SWLS.\n The results of this study suggest that complementary treatments, such as ACT and yoga, decrease seizure index and increase quality of life.", "A randomized, controlled trial was conducted in Santiago, Chile to test the impact of a child-centered, family-focused educational program for children aged 7-14 years with epilepsy and for their parents. The objectives of the program developed and pilot-tested in Los Angeles, California were to increase the children's knowledge, perceptions of competency, and skills related to dealing with seizures. Children in the experimental group (n = 123) and their parents separately attended four 1 1/2-h sessions and then met together at the end of each session to share learning experiences. Control children (n = 113) and their parents attended three 2-h sessions with a traditional lecture followed by question-and-answer format. All participants were pretested and then retested 5 months after completion of the educational intervention. Although there was some knowledge increase among children in the control group, the knowledge of children in the experimental group was significantly enhanced in a variety of areas related to management of their seizures and unnecessary restriction of their social and play activities. There was a significant increase in the self-perceptions of social competency of children in the experimental group. Children in the experimental group without serious behavioral problems also reported significantly better behavior after the intervention than did control children. There was no impact on children's disclosure of their diagnosis to friends and others.", "The study was conducted to test the feasibility of a telephone-based self-management program for adults with epilepsy. The program was based on social cognitive theory and principles of motivational interviewing (MI). Twenty-two adults with epilepsy were recruited from hospital-based epilepsy clinics. The mean age of participants was 43 years, and 68% were men. Participants were randomly assigned to the intervention or control group. Those in the intervention group received a five-session intervention with a nurse trained in MI counseling. Following an in-person introductory session, the remaining four sessions were conducted by phone. Ninety-five percent of the 55 planned MI sessions and the 44 planned courtesy calls for those in the control group were completed, demonstrating high acceptance of the program. Participants were very satisfied with the program and noted the benefits of the telephone delivery method. Analysis of outcomes provided support for continued development and testing of the program.", "nan", "Psychological interventions in the treatment of epilepsy have been developed and evaluated for many years but the amount of research has hardly made an impact on how epilepsy is treated. The purpose of this study was to develop and evaluate a psychological treatment program consisting of acceptance and commitment therapy (ACT) together with some behavioral seizure control technology shown to be successful in earlier research.\n The method consisted of a randomized controlled trial group design with repeated measures (n=27). All participants had an EEG verified epilepsy diagnosis with drug refractory seizures. Participants were randomized into one of two conditions, ACT or supportive therapy (ST). Therapeutic effects were measured by examining changes in quality of life (SWLS and WHOQOL) and seizure index (frequency x duration). Both treatment conditions consisted of only nine hours of professional therapy distributed in two individual and two group sessions during a four-week period.\n The results showed significant effects over all of the dependent variables for the ACT group as compared to the ST group at six- and twelve-month follow-ups.\n The results from this study suggest that a short-term psychotherapy program combined with anticonvulsant drugs may help to prevent the long-term disability that occurs from drug refractory seizures.", "The goal of the work described in this article was to test the possibility of preventing depression among adolescents with epilepsy.\n Adolescents with newly diagnosed epilepsy (104 patients) were screened for depression. The risk for depression was increased in 30 (28.8%) patients (mean age 17.4, 60% females) who were randomized into two equal treatment groups: (1) cognitive-behavioral intervention (CBI) group and (2) treatment with counseling as usual (TAU) group. The Beck Depression Inventory (BDI), Center for Epidemiological Study on Depression (CES-D) scale, Hamilton Depression Scale (HAMD), and Quality of Life in Epilepsy Inventory (QOLIE-31) were administered at baseline and during the 9-month follow-up.\n Initial BDI and HAMD scores for the two groups were comparable. Depression was diagnosed during follow-up in three patients in the TAU group. Subthreshold depressive disorder significantly improved at follow-up in the BCI group compared with the TAU group (P<0.05). QOLIE-31 Total scores significantly correlated with both mood improvement and seizure-free state.", "The present study evaluated the efficacy of group cognitive-behavior therapy for the alleviation of psychosocial problems and reduction of seizures with adult epileptic patients. Twenty-seven outpatients were randomly assigned to one of three groups: Cognitive-Behavior Therapy, Supportive Counseling (attention-placebo control), and Waiting list (no treatment control). The major outcome measures used were: patient's, neurologist's, and therapist's global ratings of psychological adjustment, patient's target complaints and weekly seizure frequency, patient's and neurologist's ratings of seizure control, the Minnesota Multiphasic Personality Inventory, the Washington Psychosocial Seizure Inventory, and the Beck Depression Inventory. No significant differences were found among the three groups on these measures except for therapist's global ratings of psychological adjustment, on which both the Cognitive-Behavior Therapy and Supportive Counseling groups improved significantly after therapy, but the Waiting List control group did not. Overall, little support was found for the efficacy of group cognitive behavior therapy (eight 2-h weekly sessions) for the reduction of psychosocial difficulties or seizures. Implications of the present findings are discussed, with the need for further controlled outcome research stressed.", "A group of eighteen adults with refractory epileptic seizures were given psychological treatment in a two-phase experimental group study. In phase one, the experimental phase, the patients were divided into three groups--contingent relaxation (CR), attention control (ATC) treatment, and a no-treatment (NT) control group--with the purpose of investigating the effects of a learning-based contingent relaxation program compared with the effects of professional attention alone when superimposed on a regular medical treatment program. The design of the experimental phase was comprised of a 10-week baseline, 6-week intervention, and 10-week follow-up. Results of this phase at the end of follow-up showed a significant reduction only for those patients receiving the CR treatment. In the nonexperimental phase, the two control groups also received the CR treatment for a 6-week period, and subsequent seizure frequency measures for all three groups were analyzed after 10-week and 30-week follow-up periods. Results of this phase showed a significant reduction in seizure frequency for all three groups after receiving the CR treatment. Effects of the CR treatment were maintained at a 30-week follow-up. The results indicate that the CR treatment program may be of substantial help to adults whose seizures are resistant to conventional drug therapy.", "The goal of the work described here was to develop and pilot a theoretically based self-management intervention in adults with epilepsy.\n A randomized, controlled trial examined intervention effectiveness of a 6-week psychosocial intervention designed to improve self-efficacy and quality of life for 61 adults with diagnosed epilepsy. Measures included the Quality of Life in Epilepsy-89 inventory (QOLIE-89), the Washington Psychosocial Seizure Inventory (WPSI), a locus of control scale (LOC), and the Epilepsy Self-Efficacy Scale-2000 (ESES). Group differences were examined between groups using analysis of covariance.\n There was a significant improvement in the QOLIE-89 Role Limitations-Emotional score in the treatment group at follow-up, but no significant differences in overall quality of life. Strong and significant correlations were observed between outcome measures.\n Although the intervention had little effect on improving overall quality of life, we observed promising trends in postintervention group comparisons linking self-efficacy and other psychosocial factors with quality of life. Intervention material can be modified for stage-based behavior change and retested in another study." ]

[ "11113085", "20102716" ]

[ "Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial.", "Pentoxifylline does not decrease short-term mortality but does reduce complications in patients with advanced cirrhosis." ]

[ "An earlier pilot study from our liver unit suggested benefit from treatment with pentoxifylline (PTX), an inhibitor of tumor necrosis factor (TNF), in severe acute alcoholic hepatitis. The aim of the present study was to evaluate this treatment in a larger cohort of patients.\n One hundred one patients with severe alcoholic hepatitis (Maddrey discriminant factor > or = 32) entered a 4-week double-blind randomized trial of PTX (400 mg orally 3 times daily) vs. placebo. Primary endpoints of the study were the effect of PTX on (1) short-term survival and (2) progression to hepatorenal syndrome. On randomization, there were no differences in demographic and clinical characteristics or laboratory values (including TNF) between the 2 groups.\n Twelve (24.5%) of the 49 patients who received PTX and 24 (46.1%) of the 52 patients who received placebo died during the index hospitalization (P = 0.037; relative risk, 0.59; 95% confidence interval, 0.35-0.97). Hepatorenal syndrome was the cause of death in 6 (50%) and 22 (91.7%) patients (P = 0.009; relative risk, 0.29; 95% confidence interval, 0.13-0.65). Three variables (age, creatinine level on randomization, and treatment with PTX) were independently associated with survival. TNF values on randomization were not predictive of survival; however, during the study period they increased markedly in nonsurvivors compared with survivors in both groups.\n Treatment with PTX improves short-term survival in patients with severe alcoholic hepatitis. The benefit appears to be related to a significant decrease in the risk of developing hepatorenal syndrome. Increasing TNF levels during the hospital course are associated with an increase in mortality rate.", "Pentoxifylline, an inhibitor of tumor necrosis factor-alpha, is given to patients with liver diseases, but its effects in patients with advanced cirrhosis are unknown. We performed a randomized, placebo-controlled, double-blind trial of its effects in patients with cirrhosis.\n A total of 335 patients with cirrhosis (Child-Pugh class C) were assigned to groups given either pentoxifylline (400 mg, orally, 3 times daily; n = 164) or placebo (n = 171) for 6 months. The primary end point was mortality at 2 months. Secondary end points were mortality at 6 months and development of liver-related complications.\n By 2 months, 28 patients in the pentoxifylline group (16.5%) and 31 in the placebo group (18.2%) had died (P = .84). At 6 months, 50 patients in the pentoxifylline group (30.0%) and 54 in the placebo group (31.5%) had died (P = .75). The proportions of patients without complications (eg, bacterial infection, renal insufficiency, hepatic encephalopathy, or gastrointestinal hemorrhage) were higher in the pentoxifylline group than in the placebo group at 2 months (78.6% vs 63.4%; P = .006) and 6 months (66.8% vs 49.7%; P = .002). The probability of survival without complications was higher in the pentoxifylline group than in the placebo group at 2 and 6 months (P = .04). In multivariate analysis, the factors associated with death were age, the Model for End-Stage Liver Disease score, and presence of early-stage carcinoma. Treatment with pentoxifylline was the only factor associated with liver-related complications.\n Although pentoxifylline does not decrease short-term mortality in patients with advanced cirrhosis, it does reduce the risk of complications.\n Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved." ]