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[ "3321864" ]

[ "The effect of bedrest in hospital on fetal outcome in pregnancies complicated by intra-uterine growth retardation." ]

[ "A prospective study was made to evaluate whether bedrest in hospital is beneficial in pregnancies where intra-uterine growth retardation (IUGR) was suspected. Diagnosis was based on routine fetometry at 32 weeks of gestation, in conjunction with general ultrasound screening. 107 patients with suspected IUGR-pregnancies were divided into two groups, 49 in a hospital bedrest group and 58 in an 'out-patient' group. Fifteen women in the bedrest group refused hospitalization, and 8 women in the out-patient group had to be hospitalized for medical reasons other than suspected growth retardation, leaving 79% of the women in their allocated group. The women in the bedrest group were hospitalized for a mean duration of 29.2 days (range 5-54). The results suggest that bedrest in hospital is not beneficial, either to fetal growth or to pregnancy outcome." ]

[ "16259492", "11679471", "12196430", "9314625", "16298697", "17364900", "15946117", "11815493", "9219407", "16709243" ]

[ "Evaluating a problem-based empowerment program for African Americans with diabetes: results of a randomized controlled trial.", "Effectiveness of culture-specific diabetes care for Surinam South Asian patients in the Hague: a randomized controlled trial/controlled before-and-after study.", "A randomized trial of an intervention to improve self-care behaviors of African-American women with type 2 diabetes: impact on physical activity.", "A randomized controlled trial of weight reduction and exercise for diabetes management in older African-American subjects.", "Symptom-focused management for African American women with Type 2 diabetes: a pilot study.", "Assessment of two culturally competent diabetes education methods: individual versus individual plus group education in Canadian Portuguese adults with type 2 diabetes.", "Diabetes self-management among low-income Spanish-speaking patients: a pilot study.", "Culturally competent diabetes self-management education for Mexican Americans: the Starr County border health initiative.", "One-to-one teaching with pictures--flashcard health education for British Asians with diabetes.", "A controlled trial of the effectiveness of a diabetes education programme in a multi-ethnic community in Glasgow [ISRCTN28317455]." ]

[ "The objective of this study was to evaluate the impact of a problem-based empowerment patient education program specifically tailored for urban African Americans with type 2 diabetes.\n The study used a randomized controlled trial (RCT) pretest/post-test design with repeated measures. Patients were randomly assigned to either a six-week intervention group or a six-week wait-listed control group. After completing the six sessions, patients were invited to participate in one of two follow-up conditions; attend a monthly support group or receive a monthly phone call from a nurse. Assessment measures included HbA1C, lipids, blood pressure, weight, self-management behavior and psychosocial adaptation.\n Both control and intervention patients showed a broad array of small-to-modest positive changes during the six-week RCT. These gains were maintained or improved upon during the one-year follow-up period. For patients in the two follow-up conditions, a positive correlation was seen between the number of follow-up contacts and their one-year HbA1C values.\n We believe that results of this study can be attributed to volunteer bias, study effects (ie, providing study data on several occasions to patients and their physicians during the one-year study period), and impact of the interventions. However, the study design does not allow us to examine the relative impact of these three factors on the patient improvements seen over the one-year study period.", "nan", "To determine whether a culturally appropriate clinic- and community-based intervention for African-American women with type 2 diabetes will increase moderate-intensity physical activity (PA).\n In this randomized controlled trial conducted at seven practices in central North Carolina, 200 African-American women, > or =40 years of age with type 2 diabetes, were randomized to one of three treatment conditions: clinic and community (group A), clinic only (group B), or minimal intervention (group C). The clinic-based intervention (groups A and B) consisted of four monthly visits with a nutritionist who provided counseling to enhance PA and dietary intake that was tailored to baseline practices and attitudes; the community-based intervention (group A) consisted of three group sessions and 12 monthly phone calls from a peer counselor and was designed to provide social support and reinforce behavior change goals; and the minimal intervention (group C) consisted of educational pamphlets mailed to participants. The primary study outcome was the comparison of PA levels between groups assessed at 6 and 12 months by accelerometer, which was worn while awake for 7 days.\n Totals of 175 (88%) and 167 (84%) participants completed PA assessment at 6 and 12 months, respectively. For comparison of PA, the P value for overall group effect was 0.014. Comparing group A with C, the difference in the average adjusted mean for PA was 44.1 kcal/day (95% CI 13.1-75.1, P = 0.0055). Comparing group B with C, the difference in the average adjusted mean was 33.1 kcal/day (95% CI 3.3-62.8, P = 0.029). The intervention was acceptable to participants: 88% were very satisfied with clinic-based counseling to enhance PA, and 86% indicated that the peer counselor's role in the program was important.\n The intervention was associated with a modest enhancement of PA and was acceptable to participants.", "To evaluate a weight loss and exercise program designed to improve diabetes management in older African-Americans.\n Overweight African-Americans (n = 64) ages 55-79 years with NIDDM were randomized to either an intervention (12 weekly group sessions, 1 individual session, and 6 biweekly group sessions) or usual care (1 individual session, and 6 biweekly group sessions) or usual care (1 class and 2 informational mailings). Clinical and behavioral variables were assessed at 0, 3, and 6 months of treatment.\n Significant net differences in the intervention versus usual care were observed for weight (-2.0 kg, P = 0.006), physical activity, and dietary intake of fat, saturated fat, cholesterol, and nutrition knowledge at 3 months (all P < 0.05) and for weight at 6 months (-2.4 kg; P = 0.006) and mean HbA1c values at 3 and 6 months (respectively, -1.6 and -2.4%, both P < 0.01). After the adjustment for changes in weight and activity, the intervention participants were approximately twice as likely to have a one unit decrease in HbA1c value as those in usual care. Blood pressure increase sin usual care participants resulted in net differences (intervention minus control) at 3 and 6 months of -3.3 (P = 0.09) and -4.0 (P = 0.05) mmHg diastolic, respectively, and -8.4 (P = 0.06) and -5.9 (P > 0.10) mmHg systolic, respectively. Blood lipid profiles improved more in intervention than usual care participants, but not significantly.\n The intervention program was effective in improving glycemic and blood pressure control. The decrease in HbA1c values was generally independent of the relatively modest changes in dietary intake, weight, and activity and may reflect indirect program effects on other aspects of self-care.", "The purpose of this pilot study was to test the effectiveness of an in-home, nurse-delivered, symptom-focused teaching/counseling intervention with older rural African American women who have type 2 diabetes. Forty-one participants were randomly assigned to either the intervention or the comparison group. Participants in the intervention showed statistically significant improvement in their medication, diet, home glucose monitoring self-care practices, perceptions of quality of life, and distress from symptoms. Both groups evidenced improvement of HbA(1c) levels. The intervention group achieved greater improvement, but the difference was not statistically significant. Participant satisfaction was high. Further studies should look into the cost of the intervention, as compared with that of usual care, and its long-term effects.", "To examine the impact of two culturally competent diabetes education methods, individual counselling and individual counselling in conjunction with group education, on nutrition adherence and glycemic control in Portuguese Canadian adults with type 2 diabetes over a three-month period.\n The Diabetes Education Centre is located in the urban multicultural city of Toronto, Ontario, Canada. We used a three-month randomized controlled trial design. Eligible Portuguese-speaking adults with type 2 diabetes were randomly assigned to receive either diabetes education counselling only (control group) or counselling in conjunction with group education (intervention group). Of the 61 patients who completed the study, 36 were in the counselling only and 25 in the counselling with group education intervention. We used a per-protocol analysis to examine the efficacy of the two educational approaches on nutrition adherence and glycemic control; paired t-tests to compare results within groups and analysis of covariance (ACOVA) to compare outcomes between groups adjusting for baseline measures. The Theory of Planned Behaviour was used to describe the behavioural mechanisms that influenced nutrition adherence.\n Attitudes, subjective norms, perceived behaviour control, and intentions towards nutrition adherence, self-reported nutrition adherence and glycemic control significantly improved in both groups, over the three-month study period. Yet, those receiving individual counselling with group education showed greater improvement in all measures with the exception of glycemic control, where no significant difference was found between the two groups at three months.\n Our study findings provide preliminary evidence that culturally competent group education in conjunction with individual counselling may be more efficacious in shaping eating behaviours than individual counselling alone for Canadian Portuguese adults with type 2 diabetes. However, larger longitudinal studies are needed to determine the most efficacious education method to sustain long-term nutrition adherence and glycemic control.", "The prevalence of type 2 diabetes and diabetes-related morbidity and mortality is higher among low-income Hispanics when compared to that of Whites. However, little is known about how to effectively promote self-management in this population.\n The objectives were first to determine the feasibility of conducting a randomized clinical trial of an innovative self-management intervention to improve metabolic control in low-income Spanish-speaking individuals with type 2 diabetes and second to obtain preliminary data of possible intervention effects.\n Participants for this pilot study were recruited from a community health center, an elder program, and a community-wide database developed by the community health center, in collaboration with other agencies serving the community, by surveying households in the entire community. Participants were randomly assigned to an intervention (n = 15) or a control (n = 10) condition. Assessments were conducted at baseline and at 3 months and 6 months postrandomization. The intervention consisted of 10 group sessions that targeted diabetes knowledge, attitudes, and self-management skills through culturally specific and literacy-sensitive strategies. The intervention used a cognitive-behavioral theoretical framework.\n Recruitment rates at the community health center, elder program, and community registry were 48%, 69%, and 8%, respectively. Completion rates for baseline, 3-month, and 6-month assessments were 100%, 92%, and 92%, respectively. Each intervention participant attended an average of 7.8 out of 10 sessions, and as a group the participants showed high adherence to intervention activities (93% turned in daily logs, and 80% self-monitored glucose levels at least daily). There was an overall Group x Time interaction (p = .02) indicating group differences in glycosylated hemoglobin over time. The estimated glycosylated hemoglobin decrease at 3 months for the intervention group was -0.8% (95% confidence intervals = -1.1%, -0.5%) compared with the change in the control group (p = .02). At 6 months, the decrease in the intervention group remained significant, -0.85% (95% confidence intervals = -1.2, -0.5), and the decrease was still significantly different from that of the controls (p = .005). There was a trend toward increased physical activity in the intervention group as compared to that of the control group (p = .11) and some evidence (nonsignificant) of an increase in blood glucose self-monitoring in the intervention participants but not the control participants. Adjusting for baseline depressive scores, we observed a significant difference in depressive symptoms between intervention participants and control participants at the 3-month assessment (p = .02).\n Low-income Spanish-speaking Hispanics are receptive to participate in diabetes-related research. This study shows that the pilot-tested diabetes self-management program is promising and warrants the conduct of a randomized clinical trial.", "To determine the effects of a culturally competent diabetes self-management intervention in Mexican Americans with type 2 diabetes.\n A prospective, randomized, repeated measures study was conducted on the Texas-Mexico border in Starr County. A total of 256 randomly selected individuals with type 2 diabetes between 35 and 70 years of age, diagnosed with type 2 diabetes after 35 years of age, and accompanied by a family member or friend were included. The intervention consisted of 52 contact hours over 12 months and was provided by bilingual Mexican American nurses, dietitians, and community workers. The intervention involved 3 months of weekly instructional sessions on nutrition, self-monitoring of blood glucose, exercise, and other self-care topics and 6 months of biweekly support group sessions to promote behavior changes. The approach was culturally competent in terms of language, diet, social emphasis, family participation, and incorporation of cultural health beliefs. Outcomes included indicators of metabolic control (HbA(1c) and fasting blood glucose), diabetes knowledge, and diabetes-related health beliefs.\n Experimental groups showed significantly lower levels of HbA(1c) and fasting blood glucose at 6 and 12 months and higher diabetes knowledge scores. At 6 months, the mean HbA(1c) of the experimental subjects was 1.4% below the mean of the control group; however, the mean level of the experimental subjects was still high (>10%).\n This study confirms the effectiveness of culturally competent diabetes self-management education on improving health outcomes of Mexican Americans, particularly for those individuals with HbA(1c) levels >10%.", "Type 2 diabetes is up to four times more common in British Asians, but they know little about its management and complications.\n To design and evaluate a structured pictorial teaching programme for Pakistani Moslem patients in Manchester with type 2 diabetes.\n A randomized controlled trial of pictorial flashcard one-to-one education in 201 patients attending a hospital outpatient clinic or diabetic clinics in ten general practices in Manchester. Patients' knowledge, self-caring skills and attitudes to diabetes were measured on four topics before the structured teaching, and compared with results six months later.\n All parameters of knowledge were increased in the study group; for example, percentage scores for correctly identifying different food values increased from 57% to 71% (Analysis of Variance (ANOVA) adjusted difference +11.8%) and knowledge of one diabetic complication from 18% to 78%. Self-caring behaviour improved, with 92% of patients doing regular glucose tests at six months compared with 63% at the start. Attitudinal views were more resistant to change, with patients still finding it hard to choose suitable foods at social occasions. Haemoglobin A1c control improved by 0.34% over six months (ANOVA adjusted difference, 95% CI -0.8% to +0.1%).\n It is concluded that this health education programme can empower Asian diabetics to take control of their diets, learn to monitor and interpret glucose results, and understand the implications of poor glycaemic control for diabetic complications.", "Epidemiologic data have shown that the prevalence of Type 2 diabetes varies with ethnic origin. Type 2 diabetes is up to four times more common in British South Asians than in the indigenous white population. The aim of this study was to develop a culturally appropriate educational intervention programme for South Asians with Type 2 diabetes. We then investigated whether this intervention could produce an improvement, and finally whether any improvement was greater than background changes in knowledge in comparison groups.\n A multi-site prospective, randomised controlled study was conducted in all day care centres and three general practice registers with high proportion patients from different ethnic minority groups in Glasgow, Scotland. The intervention consisted of 18 educational sessions in 6 separate programmes. A modified questionnaire was used to measure the knowledge, attitudes, and practice of diabetes before and after intervention.\n Baseline assessment showed that Indian and Pakistani subjects had less knowledge about diabetes, regarded the disease less seriously, and had a lesser understanding of the relationship between control and complications than the white population. No differences in initial responses were found between those who completed the second assessment and those who did not. The intervention group showed significant improvements in scores for Knowledge (+12.5%); Attitudes toward seriousness (+13.5%), complications (+8.1%), Practice (+20.0%). However there were also changes in the ethnic control group scores; respectively +5.0%, +16.3% (significant P < 0.001), +1.5%, +1.7%. The single white control group also showed some improvements; respectively +12.2%, +12.4% (P = 0.04), +6.0%, +25.0% (P = 0.007), but the differences in improvement between these two control groups were not significant. Overall, the improvement seen was similar in both intervention and ethnic control groups and there was no significant difference in the amount of change (P = 0.36 CI -0.9 to +2.6).\n This study has shown that conducting a culturally-competent educational intervention in patients with Type 2 diabetes from ethnic minority groups is feasible and can improve their knowledge and attitudes and practice. However there was no net benefit compared with the control group." ]

[ "7555621", "9246023", "10080053", "15730349", "16169160", "14616189", "7555622", "16930857", "7555620", "15283944", "8612392", "15730351" ]

[ "Double-blind comparison of carbamazepine and placebo for treatment of cocaine dependence.", "A randomized double-blind study of carbamazepine in the treatment of cocaine abuse.", "Effects of phenytoin on cocaine self-administration in humans.", "A placebo-controlled screening trial of olanzapine, valproate, and coenzyme Q10/L-carnitine for the treatment of cocaine dependence.", "A randomized placebo-controlled trial of gabapentin for cocaine dependence.", "Tiagabine increases cocaine-free urines in cocaine-dependent methadone-treated patients: results of a randomized pilot study.", "Carbamazepine treatment for cocaine dependence.", "Clinical efficacy of gabapentin versus tiagabine for reducing cocaine use among cocaine dependent methadone-treated patients.", "Carbamazepine treatment of cocaine dependence: a placebo-controlled trial.", "A pilot trial of topiramate for the treatment of cocaine dependence.", "Phenytoin in the treatment of cocaine abuse: a double-blind study.", "A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments." ]

[ "This study was conducted to determine the effectiveness of carbamazepine (CBZ) for treatment of cocaine dependence. Sixty-two (CBZ = 28, placebo = 34) cocaine-dependent (DSM-III-R criteria) volunteers consented to be treated for eight weeks with standardized outpatient individual counseling twice a week plus double-blind CBZ or inactive placebo. During the 8-week trial, both groups showed increased number of urine samples negative for cocaine, significantly (P < 0.01) decreased self-reported cocaine use (money spent and grams used), and decreased Beck Depression Inventory and Symptom Check List-90-Revised (SCL-90-R) total scores. However, there were no significant differences between CBZ and placebo. This study does not support the effectiveness of CBZ for outpatient treatment of cocaine dependence.", "A 12-week, randomized, double-blind, placebo-controlled, fixed-dose outpatient study of carbamazepine (400 mg and 800 mg) in the treatment of cocaine dependence was performed. Data were analyzed with respect to both treatment condition and carbamazepine serum levels. Outcome variables included subject retention, cocaine urinalysis, self-reported cocaine use, cocaine craving, patient and clinical global impressions, the Drug Impairment Rating Scale for Cocaine, and side effects. Compared with placebo, the 400 mg treatment condition exhibited a greater decrease in the rate of positive cocaine urinalyses and a reduction in intensity and duration of craving over the course of the study. Higher serum carbamazepine levels were associated with a lower rate of positive cocaine urinalysis, fewer days of self-reported cocaine use, briefer craving episodes, and greater subject interval retention. The clinical and methodologic implications of these findings and of the study design are discussed.", "The goal of this pilot study was to determine the effects of phenytoin on cocaine self-administration in a human laboratory model. Subjects were randomized to either phenytoin (n = 6) or placebo (n = 7). Those assigned to phenytoin treatment received a single oral loading dose of 20 mg/kg. The phenytoin and placebo treatment groups did not differ in the number of tokens valued at $5, exchanged for cocaine. Similarly, the cardiovascular and subjective response to cocaine administration did not show a statistically significant treatment effect. In this laboratory model, phenytoin did not alter either the self-administration or effects of cocaine.", "To conduct a medication screening trial on the efficacy of olanzapine, valproate or coenzyme Q10/L-carnitine combination versus placebo for the treatment of cocaine dependence.\n A four-arm, modified blinded, parallel group study in an out-patient setting using the Cocaine Rapid Efficacy and Safety Trials (CREST) study design.\n The study was performed at the New York Medications Development Research Unit (MDRU).\n All participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and provided at least two urine samples positive for benzoylecgonine (BE) during the 2-week screening period. Sixty-eight participants were enrolled with 39 completing the study.\n After a 2-week screening period, 68 subjects were assigned randomly to receive either olanzapine (10 mg/day), valproate (1500 mg/day), coenzyme Q10 (200 mg/day) and L-carnitine (500 mg/day) combination or placebo for an 8-week treatment period. All subjects also received individual cognitive behavioral counseling during treatment.\n Primary outcome measures included quantitative urine benzoylecgonine (BE) levels, self-report of drug use, and global impression scores. Secondary outcomes included cocaine craving, study retention and related psychosocial measures. Safety measures included adverse event monitoring, vital signs, and extrapyramidal side-effects tests.\n Study retention was similar across all treatment groups, and all groups showed improvement across most measures of treatment efficacy over the duration of the study. None of the study medications, however, were superior to placebo on any of the primary or secondary outcome measures. Cocaine use, as measured by urine BE levels and self-report, was not significantly lower than placebo in any of the drug treatment groups. All study medications were equally well tolerated, and few medication side effects were observed.\n This pilot study does not support the effectiveness of olanzapine, valproate or coenzyme Q10/L-carnitine combination for the treatment of cocaine dependence.", "In laboratory animals, augmentation of GABA neurotransmission results in inhibition of cocaine self-administration and inhibition of reinstatement to cocaine-seeking behaviors. If parallel effects were observed in humans, GABA-ergic medication should be effective both in the abstinence-induction as well as in the relapse-prevention phase of cocaine dependence treatment. Gabapentin is an anticonvulsant medication that increases human brain GABA levels. We evaluated the safety and efficacy of gabapentin combined with relapse-prevention therapy in the treatment of cocaine-dependent individuals.\n The study involved 129 individuals with cocaine dependence. Of the 99 participants, who were randomized into a double-blind trial 88% were males, 66% were minorities and with an average age of 39 years (range 22-58 years). After 2 weeks of placebo lead-in, participants were randomized to receive either gabapentin 3200 mg (1600 mg bid) or placebo for 12 weeks, followed by 2 weeks of placebo lead-out. Prior to randomization, participants were stratified into four groups based on the principal route of cocaine use (smokers versus intranasal users) and the level of cocaine use during the 2 weeks of lead-in (high level versus low level). Throughout the 16 weeks study, participants received weekly individual relapse-prevention therapy. The outcome measures included: days of cocaine use and a binary indicator of abstinence based on urine toxicology test, self-reported cocaine craving and retention in treatment.\n Forty-nine percent of randomized patients completed 12 weeks of the trial. Retention did not differ by treatment group but cocaine-smokers dropped out of treatment at a significantly faster rate than intranasal users. For the entire sample, odds of cocaine use over the course of the study did not differ between gabapentin- and placebo-treated individuals. There was a significant difference in the odds of cocaine use between high and low-use groups, with the odds in high-use groups decreasing over time and odds in the low-use groups gradually increasing over the course of the study, such that by the end of the study low and high users were similarly likely to use cocaine. In the low-use group, there was a non-significant trend suggesting that gabapentin-treated subjects had more favorable outcome compared to placebo-treated individuals. There was no treatment effect on abstinence rates, craving or other substance use. Gabapentin at 3200 mg/day was very well tolerated in this group of cocaine-dependent participants.\n When combined with weekly individual relapse-prevention therapy, gabapentin 1600 mg bid was no more effective than placebo in the treatment of cocaine dependence. When reviewed in conjunction with other published studies, gabapentin and other GABA enhancing anticonvulsant medications may deserve further study as relapse-preventive agents in cocaine-dependent individuals who achieve abstinence early in treatment.", "We sought to evaluate the safety and efficacy of the GABAergic agent tiagabine in reducing cocaine use among methadone-treated patients.\n Ten-week randomized double-blind placebo-controlled trial.\n Opiate Treatment Research Program, Veteran's Affairs Connecticut Healthcare System in West Haven, Connecticut, USA.\n The participants were 45 cocaine-dependent methadone-treated patients who were predominately Caucasian (75.6%), male (77.8%) and never married (53%) with an average age of 38 years (SD = 6.5).\n Comparison groups received tiagabine 12 mg/day (n = 15), tiagabine 24 mg/day (n = 15) or placebo (n = 15).\n Baseline assessments included the Structured Clinical Interview for DSM-IV, the Addiction Severity Index, a urine drug test, self-reported use and opiate withdrawal scales. Urine drug tests were performed thrice weekly.\n Treatment retention was over 80% for all treatment groups. The sample mean (+/- SE) of cocaine-free urines for the first week after study entry and before tiagabine was started was 1.16 (0.19) urines/week. During weeks 9 and 10 cocaine-free urines increased significantly from baseline by 33% with high-dose tiagabine (24 mg/day), by 14% with low-dose tiagabine (12 mg/day) and decreased by 10% with placebo (hierarchical linear model, Z= 2.03; P < 0.05). Self-reported cocaine use also decreased significantly more with active medications than with placebo.\n Tiagabine at 24 mg/day was well tolerated among these methadone-treated patients with only one reporting headache. Tiagabine appears to be a promising GABAergic medication that moderately improves cocaine-free urines.", "We report on a double-blind, placebo-controlled study of carbamazepine (CBZ) treatment for cocaine dependence. A previously reported uncontrolled study found CBZ to be a beneficial pharmacotherapy for cocaine dependence. Statistical analyses were performed on data from 82 subjects who were randomized to 10 weeks' treatment with either CBZ, titrated to 4-12 micrograms/ml, (n = 37) or placebo (n = 45). The two treatment groups did not differ for primary outcome measures of retention time in treatment, urine samples positive for cocaine metabolite, subject reported desire for cocaine or for subject reported side-effects. CBZ was not an effective treatment in this study.", "GABAergic medications appear to reduce the reinforcing effects of cocaine by attenuating cocaine-induced dopamine release. This study evaluated gabapentin and tiagabine compared to placebo in reducing cocaine taking behavior.\n A total of 76 treatment seeking, cocaine dependent, methadone-treated, predominately Caucasian male subjects were randomly assigned to tiagabine 24 mg/day (N=25), gabapentin 2400 mg/day (N=26) or placebo (N=25) in a 10-week double-blind placebo-controlled trial. Study medications were slowly increased to their full dosages by the end of week 5 and maintained through week 10. The primary outcome measure was thrice-weekly drug free urine samples.\n Treatment retention was significantly less for the gabapentin group relative to the other groups (log rank=5.29, d.f.=1, p=0.02). The proportion of cocaine-free urine samples during weeks 6-10 was significantly larger in the tiagabine treated group (p<0.05). The longitudinal data showed significant change in thrice-weekly cocaine free urines that reached a greater abstinent rate for the tiagabine treated group (22%) compared to gabapentin (5%) or placebo (13%) treated groups. Mixed-effects ordinal regression models showed a significant tiagabine by time interaction compared to gabapentin (Z=2.48, d.f.=1, p=0.01) and placebo (Z=3.90, d.f.=1, p=0.0001). The gabapentin group did not differ from placebo.\n Gabapentin showed poor treatment retention and ineffectiveness in reducing cocaine use. Tiagabine significantly reduced cocaine taking behavior compared to placebo or gabapentin among methadone-stabilized cocaine abusers.", "Cocaine-induced kindling, which has been hypothesized to underlie cocaine-induced craving, is reversed by carbamazepine treatment. Though preliminary studies showed carbamazepine to be useful for relapse prevention in cocaine-dependent subjects, more recent studies have failed to replicate those findings. We conducted a randomized, double-blind, placebo-controlled trial of carbamazepine 600 mg/day in 40 cocaine-dependent males. During active treatment there were no significant effects of carbamazepine on cocaine use, alcohol consumption, anxiety or depressive symptoms. At three months post-treatment carbamazepine-treated subjects reported fewer drinking days. We conclude that carbamazepine at this dose level is probably not efficacious for treatment of cocaine dependence.", "Both GABAergic and glutamatergic neurons appear to be important modulators of the brain reward system and medications that affect GABA and glutamatergic neurotransmission may reduce the rewarding properties of cocaine and reduce cocaine craving. Topiramate, an anticonvulsant, raises cerebral GABA levels, facilitates GABAergic neurotransmission and inhibits glutametergic activity at AMPA/kainite receptors. Thus, it may be useful for treating cocaine dependence.\n The efficacy of topiramate for cocaine dependence was tested in a 13-week, double-blind, placebo-controlled pilot trial (n = 40). Topiramate was titrated gradually over 8 weeks to a dose of 200 mg daily. The primary outcome measure was cocaine abstinence verified by twice weekly urine benzoylecgonine tests (UBT).\n Eighty-two percent of subjects completed the trial. Analysis of the UBT using a GEE model showed that after week 8, when the dose titration was completed, topiramate-treated subjects were more likely to be abstinent from cocaine compared to placebo-treated subjects (Z = 2.67, P = 0.01). Topiramate-treated subjects were also more likely to attain 3 weeks of continuous abstinence from cocaine (chi2 = 3.9, d.f. = 1, P = 0.05).\n Topiramate may be effective for the treatment of cocaine dependence.", "To evaluate the effectiveness of phenytoin in the treatment of cocaine abuse.\n A 12-week, double-blind, placebo-controlled outpatient study of phenytoin in the treatment of cocaine abuse was conducted. Sixty cocaine-using subjects were randomly assigned to a daily fixed dose of 300 mg phenytoin or placebo. Forty-four subjects initiated treatment and returned for weekly visits. Primary measures of outcome included weekly quantitative and qualitative cocaine urinalysis, self-reported cocaine use, global functioning and improvement, craving intensity, and subject retention.\n Cocaine use, as measured both by weekly urinalysis and self-report, was significantly lower in the phenytoin group. The phenytoin group was also rated as significantly less impaired and more improved than the placebo group. Craving intensity was lower in the phenytoin group, but the difference was not statistically significant. Among phenytoin subjects, serum phenytoin levels above 6.0 micrograms/ml were associated with lower rates of positive cocaine urine specimens and longer cocaine-free periods. No differences were observed between groups in study retention.\n These findings suggest that phenytoin may be useful in the treatment of cocaine abuse. Further studies are needed to replicate these findings.", "To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence.\n A 10-week out-patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.\n This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio.\n Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty-seven participants were enrolled with 55 completing final study measures.\n The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis.\n Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale-Observer and self-report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests.\n Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5-8 (P = 0.10) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures.\n The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment." ]

[ "15914981" ]

[ "A clinical trial of a slow-releasing fluoride device in children." ]

[ "The objective was to test a fluoride-containing slow-release device in preventing dental caries in children. Accordingly a population of 174 children aged 8 years living in a high-caries, low socio-economic area of Leeds (UK) was assembled. Two slow-release/dissolving glass (SFG) pellets, one with fluoride (F) and one without, were randomly attached to the maxillary molars of the children. Baseline caries as dmft/s, DMFT/S, periodontal disease, plaque and calculus were recorded using standard indices. Unstimulated saliva samples were collected 2 h postprandial for F analysis. All parameters were measured at 6-month intervals for 2 years. There were 132 children completing the trial of whom 63 (test n = 31, control n = 32) still retained the glass devices at the end. Comparison of mean values for gingival health and calculus showed no differences between groups throughout the trial. Mean caries as dmfs at the end of the trial (2.26) was significantly lower for the test (SFG, 2.26) compared with that for the control children (8.41; p < or = 0.001). DMFS was significantly lower at 0.84 and 2.34, respectively (p < or = 0.05). Mean salivary fluoride concentrations were 0.11 and 0.03 mg/l for test and control groups. It was concluded that placement of a glass slow-releasing fluoride device significantly reduced caries incidence in a group of low socio-economic schoolchildren over 2 years.\n Copyright (c) 2005 S. Karger AG, Basel." ]

[ "15724802" ]

[ "Treatment effect of sibutramine compared to fluoxetine on leptin levels in polycystic ovary disease." ]

[ "Weight reduction on its own is observed to cause improvement in some of the abnormalities seen in patients with polycystic ovary syndrome (PCOS). With respect to this observation, we studied the possible effects of different serotonin reuptake inhibitors (fluoxetine and sibutramine) on serum leptin levels that might play a role in the obesity component seen in patients with PCOS. In a random design, sixteen patients were assigned to fluoxetine and sibutramine for a period of 10 days. In both treatment groups, no significant differences were observed between pre-treatment and post-treatment values in insulin levels (p > 0.05). There was no significant difference between pretreatment and post-treatment serum leptin levels in the fluoxetine treatment group (p > 0.05). However, a significant reduction was observed in the serum leptin levels at the end of treatment in the sibutramine group (p < 0.05). The observed difference in the serum leptin response to the treatment effect of sibutramine compared to fluoxetine seems to be due to a mechanism independent of serotonin reuptake inhibition, possibly to the thermogenic effect of the sibutramine itself. Further studies with larger groups are warranted, to examine the mechanism of the weight-reducing effect of sibutramine. Detailed analyses of basal metabolic activity and change in serum leptin levels should be carried out." ]

[ "12429759", "15494330", "12931804", "15570782", "15090392", "15930540", "12382950" ]

[ "Extracorporeal shock wave therapy in the treatment of lateral epicondylitis : a randomized multicenter trial.", "Effectiveness of extracorporeal shock wave therapy in the treatment of previously untreated lateral epicondylitis: a randomized controlled trial.", "Extracorporeal shock-wave treatment for tennis elbow. A randomised double-blind study.", "The use of a mobile lithotripter in the treatment of tennis elbow and plantar fasciitis.", "Repetitive low-energy shock wave treatment for chronic lateral epicondylitis in tennis players.", "Extracorporeal shock wave therapy without local anesthesia for chronic lateral epicondylitis.", "Extracorporeal shock wave therapy for lateral epicondylitis--a double blind randomised controlled trial." ]

[ "On the basis of observational trials, numerous investigators have recommended extracorporeal shock wave therapy as an alternative treatment for chronic lateral epicondylitis of the elbow. However, there has been no evidence of its efficacy from well-designed randomized clinical trials. The objective of this study was to find out whether extracorporeal shock wave therapy in combination with local anesthesia was superior to placebo therapy in combination with local anesthesia.\n A randomized multicenter trial with a parallel-group design was conducted. Following administration of local anesthesia, either extracorporeal shock wave therapy with three treatments of 2000 pulses each and a positive energy flux density (ED+) of 0.07 to 0.09 mJ/mm (2) or placebo therapy was applied on an outpatient basis. Treatment allocation was blinded for patients and for observers. The primary end point was based on the rate of success, as determined with the Roles and Maudsley score and whether additional treatment was required, twelve weeks after the intervention. Crossover was possible after assessment of the primary end point. Secondary end points were the Roles and Maudsley score, subjective pain rating, and grip strength after six and twelve weeks and after twelve months. The planned number of 272 patients was included in the study.\n The primary end point could be assessed for 90.8% of the patients. The success rate was 25.8% in the group treated with extracorporeal shock wave therapy and 25.4% in the placebo group, a difference of 0.4% with a 95% confidence interval of -10.5% to 11.3%. Similarly, there was no relevant difference between groups with regard to the secondary end points. Improvement was observed in two-thirds of the patients from both groups twelve months after the intervention. Few side effects were reported.\n Extracorporeal shock wave therapy as applied in the present study was ineffective in the treatment of lateral epicondylitis. The previously reported success of this therapy appears to be attributable to inappropriate study designs. Different application protocols might improve clinical outcome. We recommend that extracorporeal shock wave therapy be applied only in high-quality clinical trials until it is proved to be effective.", "Extracorporeal shock wave therapy is a relatively new therapy used in the treatment of chronic tendon-related pain. Few randomized controlled trials have been performed on it, and no studies have examined the effectiveness of extracorporeal shock wave therapy as a frontline therapy for tendon-related pain.\n Subjects treated with active extracorporeal shock wave therapy will have higher rates of treatment success than subjects treated with sham extracorporeal shock wave therapy.\n Double-blind randomized controlled trial.\n Sixty subjects who had previously untreated lateral epicondylitis for less than 1 year and more than 3 weeks were included in this study. Subjects were randomly allocated to receive 1 session per week for 3 weeks of either sham or active extra-corporeal shock wave therapy. Subjects in the active therapy group received 2000 pulses (energy flux density, 0.03-0.17 mJ/mm(2)). All subjects were provided with a forearm-stretching program. After 8 weeks of therapy, subjects were classified as either treatment successes or treatment failures according to fulfillment of all 3 criteria: (1) at least a 50% reduction in the overall pain visual analog scale score, (2) a maximum allowable overall pain visual analog scale score of 4.0 cm, and (3) no use of pain medication for elbow pain for 2 weeks before the 8 week follow-up. Visual analog scale scores were also collected for pain at rest, during sleep, during activity, at its worst, and at its least, as well as for quality of life (using the EuroQoL questionnaire) and grip strength.\n Success rates in the sham and active therapy groups were 31% and 39%, respectively. No significant difference was detected between groups (chi(2)(1)= 0.3880, P = .533). Mean change in quality of life over 8 weeks was an increase of 1.3 and 3.3 for sham and active therapy groups, respectively, and mean change in grip strength over 8 weeks was an increase of 7.4 kg and 6.8 kg for sham and active therapy groups, respectively.\n Despite improvement in pain scores and pain-free maximum grip strength within groups, there does not appear to be a meaningful difference between treating lateral epicondylitis with extracorporeal shock wave therapy combined with forearm-stretching program and treating with forearm-stretching program alone, with respect to resolving pain within an 8-week period of commencing treatment.", "The efficacy of extracorporeal shock-wave therapy for tennis elbow was investigated using a single fractionated dosage in a randomised, double-blind study. Outcomes were assessed using the Disabilities of Arm, Shoulder and Hand questionnaire, measurements of grip strength, levels of pain, analgesic usage and the rate of progression to surgery. Informed consent was obtained before patients were randomised to either the treatment or placebo group. In the final assessment, 74 patients (31 men and 43 women) with a mean age of 43.4 years (35 to 71), were included. None of the outcome measures showed a statistically significant difference between the treatment and control groups (p > 0.05). All patients improved significantly over time, regardless of treatment. Our study showed no evidence that extracorporeal shock-wave therapy for tennis elbow is better than placebo.", "To evaluate the use of the mobile lithotripter in the treatment of tennis elbow and plantar fasciitis.\n A prospective single blind randomised trial was performed on 24 patients with tennis elbow and 23 patients with plantar fasciitis, with a mean duration of symptoms of 11 months. All patients had failed one or more method of treatment--conservative, topical non-steriodal anti-inflammatory drugs (NSAID), steroid injection and/or surgery. The patients were divided into treatment and placebo groups. The placebo group received treatment with a clasp on the elbow/heel to stop penetration of shock waves. A baseline pain score was obtained using the Million Visual Analogue scale (0-10). The affected area was infiltrated with 3-5mls of 1% lignocaine. The treatment consisted of 2000 shock waves at 2.5 bars of air pressure with a frequency of 8-10Hz. A total of three treatments were given at an interval of two weeks, each lasting for three to four minutes.\n In the treatment groups, a final pain score at six months post treatment showed significant improvement (three or more points) in 78% of patients with tennis elbow and 93% of patients with plantar fasciitis. In the placebo groups, significant improvement was seen in one patient (9%) with tennis elbow. The other patients in the placebo groups did not show significant improvement. This was statistically significant (chi square test) for both conditions.\n The mobile lithotripter is an effective way of treating tennis elbow and plantar fasciitis but warrants further larger studies.", "There is conflicting evidence regarding extracorporeal shock wave treatment for chronic tennis elbow.\n Treatment with repetitive low-energy extracorporeal shock wave treatment is superior to repetitive placebo extra-corporeal shock wave treatment.\n Seventy-eight patients enrolled in a placebo-controlled trial. All patients were tennis players with recalcitrant MRI-confirmed tennis elbow of at least 12 months' duration. Patients were randomly assigned to receive either active low-energy extracorporeal shock wave treatment given weekly for 3 weeks (treatment group 1) or an identical placebo extracorporeal shock wave treatment (sham group 2). Main outcome measure was pain during resisted wrist extension at 3 months; secondary measures were >50% reduction of pain and the Upper Extremity Function Scale.\n At 3 months, there was a significantly higher improvement in pain during resisted wrist extension in group 1 than in group 2 (mean [SD] improvement, 3.5 [2.0] and 2.0 [1.9]; P =.001 for between-group difference of improvement) and in the Upper Extremity Function Scale (mean [SD] improvement, 23.4 [14.8] and 10.9 [14.9]; P <.001 for between-group difference of improvement). In the treatment group, 65% of patients achieved at least a 50% reduction of pain, compared with 28% of patients in the sham group (P =.001 for between-group difference).\n Low-energy extracorporeal shock wave treatment as applied is superior to sham treatment for tennis elbow.", "The use of extracorporeal shock wave therapy for the treatment of lateral epicondylitis is controversial. The purpose of this study was to evaluate the use of extracorporeal shock wave therapy without local anesthesia to treat chronic lateral epicondylitis.\n One hundred and fourteen patients with a minimum six-month history of lateral epicondylitis that was unresponsive to conventional therapy were randomized into double-blind active treatment and placebo groups. The protocol consisted of three weekly treatments of either low-dose shock wave therapy without anesthetic or a sham treatment. Patients had a physical examination, including provocation testing and dynamometry, at one, four, eight, and twelve weeks and at six and twelve months after treatment. Radiographs, laboratory studies, and electrocardiograms were also evaluated prior to participation and at twelve weeks. A visual analog scale was used to evaluate pain, and an upper extremity functional scale was used to assess function. Crossover to active treatment was initiated for nonresponsive patients who had received the placebo and met the inclusion criteria after twelve weeks.\n A total of 108 of the 114 randomized patients completed all treatments and the twelve weeks of follow-up required by the protocol. Sixty-one patients completed one year of follow-up, whereas thirty-four patients crossed over to receive active treatment. A significant difference (p = 0.001) in pain reduction was observed at twelve weeks in the intent-to-treat cohort, with an improvement in the pain score of at least 50% seen in 61% (thirty-four) of the fifty-six patients in the active treatment group who were treated according to protocol compared with 29% (seventeen) of the fifty-eight subjects in the placebo group. This improvement persisted in those followed to one year. Functional activity scores, activity-specific evaluation, and the overall impression of the disease state all showed significant improvement as well (p < 0.05). Crossover patients also showed significant improvement after twelve weeks of active treatment, with 56% (nineteen of thirty-four) achieving an improvement in the pain score of at least 50% (p < 0.0001).\n These results demonstrate that low-dose shock wave therapy without anesthetic is a safe and effective treatment for chronic lateral epicondylitis.", "Extracorporeal shock wave therapy (ESWT) is an increasingly popular therapeutic approach to the treatment of a number of soft tissue complaints. Whilst benefit has been demonstrated in calcific tendinitis, evidence is lacking for benefit in the management of non-calcific rotator cuff disorders.\n To perform a double-blind placebo controlled trial of moderate dose ESWT in chronic lateral epicondylitis.\n Adults with lateral epicondylitis were randomised to receive either active treatment (1500 pulses ESWT at 0.12 mJ/ mm2) or sham therapy, monthly for three months. All were assessed before each treatment and one month after completion of therapy. Outcome measures consisted of visual analogue scores for pain in the day and at night.\n Seventy-five subjects participated and there were no significant differences between the two groups at baseline. The mean duration of symptoms was 15.9 and 12 months in the ESWT and sham groups, respectively. Both groups showed significant improvements from two months. No significant difference existed between the groups with respect to the degrees of change in pain scores over the study period. In the ESWT group the mean (SD, range) pain score was 73.4 (14.5, 38-99) at baseline and 47.9 (31.4, 3-100) at three months. In the sham group the mean (SD, range) pain score was 67.2 (21.7, 12-100) at baseline and 51.5 (32.5, 3-100) at three months. At three months, 50% improvement from baseline was noted in 35% of the ESWT group and 34% of the sham group with respect to pain.\n There appears to be a significant placebo effect of moderate dose ESWT in subjects with lateral epicondylitis but there is no evidence of added benefit of treatment when compared to sham therapy." ]

[ "19400893", "19800680" ]

[ "Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo-controlled feasibility study.", "Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial." ]

[ "Epidemiological evidence suggests that hookworm infection protects against asthma. However, for ethical and safety reasons, before testing this hypothesis in a clinical trial in asthma it is necessary to establish whether experimental hookworm infection might exacerbate airway responsiveness during larval lung migration.\n To determine whether hookworm larval migration through the lungs increases airway responsiveness in allergic individuals with measurable airway responsiveness but not clinical asthma, and investigate the general tolerability of infection and effect on allergic symptoms.\n Thirty individuals with allergic rhinoconjunctivitis and measurable airway responsiveness to adenosine monophosphate (AMP) but not clinically diagnosed asthma were randomized, double-blind to cutaneous administration of either 10 hookworm larvae or histamine placebo, and followed for 12 weeks. The primary outcome was the maximum fall from baseline in provocative dose of inhaled AMP required to reduce 1-s forced expiratory volume by 10% (PD(10)AMP) measured at any time over the 4 weeks after active or placebo infection. Secondary outcomes included peak flow variability in the 4 weeks after infection, rhinoconjunctivitis symptom severity and adverse effect diary scores over the 12-week study period, and change in allergen skin test responses between baseline and 12 weeks.\n Mean maximum change in PD(10)AMP from baseline was slightly but not significantly greater in the hookworm than the placebo group (-1.67 and -1.16 doubling doses; mean difference -0.51, 95% confidence interval -1.80 to 0.78, P=0.42). Symptom scores of potential adverse effects were more commonly reported in the hookworm group, but infection was generally well tolerated. There were no significant differences in peak-flow variability, rhinoconjunctivitis symptoms or skin test responses between groups.\n Hookworm infection did not cause clinically significant exacerbation of airway responsiveness and was well tolerated. Suitably powered trials are now indicated to determine the clinical effectiveness of hookworm infection in allergic rhinoconjunctivitis and asthma.", "Parasitic helminth infections can protect against allergic airway inflammation in experimental models and have been associated with a reduced risk of atopy and a reduced course of asthma in some observational studies. Although no clinical evidence exists to support the use of helminth therapy for allergic disease, the helminth Trichuris suis has demonstrated efficacy in treatment of inflammatory bowel disease.\n To determine efficacy of helminth therapy for allergic rhinitis.\n We conducted a double-blind, placebo-controlled, parallel group trial in which 100 subjects age 18 to 65 years with grass pollen-induced allergic rhinitis were randomly assigned to ingest a total of 8 doses with 2500 live T suis ova or placebo with an interval of 21 days. The primary outcome was a change in mean daily total symptom score for runny, itchy, sneezing nose (maximum change, 9.0) or in percentage of well days during the grass pollen season.\n Treatment with T suis ova (N = 49) compared with placebo (N = 47) caused transient diarrhea peaking at day 41 in 33% of participants (placebo, 2%), and increased eosinophil counts (P < .001) and T suis-specific IgE (P < .05), IgG (P < .001), IgG(4) (P < .003), and IgA (P < .001), whereas there was no significant change in symptom scores (0.0; 95% CI, -0.5 to 0.4; P = .87), well days (3%; 95% CI, -9% to 14%; P = .63), total histamine (P = .44), grass-specific IgE (P = .76), or diameter of wheal reaction on skin prick testing with grass (P = .85) or 9 other allergens.\n Repeated treatment with the helminth T suis induced a substantial clinical and immunologic response as evidence of infection, but had no therapeutic effect on allergic rhinitis.\n Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved." ]

[ "10964269", "17255227", "11847921", "9735932" ]

[ "Indoor residual spraying with alphacypermethrin controls malaria in Pakistan: a community-randomized trial.", "Seven years of regional malaria control collaboration--Mozambique, South Africa, and Swaziland.", "Malaria control--two years' use of insecticide-treated bednets compared with insecticide house spraying in KwaZulu-Natal.", "A comparison of use of a pyrethroid either for house spraying or for bednet treatment against malaria vectors." ]

[ "We conducted a community-randomized controlled trial in Pakistan to determine the efficacy of indoor residual spraying with alphacypermethrin ('Fendona', Cyanamid, NJ, USA), applied at 25 mg/m2, to prevent falciparum and vivax malaria. Wettable powder (WP) and suspension concentrate (SC) formulations were tested against an unsprayed control in an irrigated rice-growing area of Sheikhupura district, Punjab province. The study area of 180 km2 was divided into nine sectors, which were assigned at random to control, WP, or SC treatments in replicates of 3. Sentinel villages were selected from each sector for entomological and disease monitoring. Malaria was monitored by fortnightly active case detection (ACD) and by cross- sectional parasite surveys on schoolchildren. Mosquito populations were monitored by space spraying of rooms and by cattle-landing catches. The spray campaign took place in June 1997 and covered 96% of compounds. During the 7 months after spraying, the incidence of falciparum malaria was 95% lower and that of vivax malaria 80% lower in WP-sprayed than unsprayed sectors. Similar results were obtained for sectors sprayed with the SC formulation. Cross-sectional surveys gave estimates of efficacy comparable to those obtained by ACD. Anopheles culicifacies was 80% less abundant and A.stephensi, the predominant anopheline, was up to 68% less abundant in sprayed areas over the 7-month period. Reductions in anopheline parous rates indicated that the single-spray treatment was effective for the entire transmission season. Sprayed surfaces lacked odour, which contributed to the popularity of the campaign. Alphacypermethrin is a promising insecticide for the control of malaria in Pakistan and South Asia generally.", "The Lubombo Spatial Development Initiative is a joint development program between the governments of Mozambique, Swaziland, and South Africa, which includes malaria control as a core component of the initiative. Vector control through indoor residual spraying (IRS) was incrementally introduced in southern Mozambique between November 2000 and February 2004. Surveillance to monitor its impact was conducted by annual cross-sectional surveys to assess the prevalence of Plasmodium falciparum infection, entomologic monitoring, and malaria case notification in neighboring South Africa and Swaziland. In southern Mozambique, there was a significant reduction in P. falciparum prevalence after the implementation of IRS, with an overall relative risk of 0.74 for each intervention year (P < 0.001), ranging from 0.66 after the first year to 0.93 after the fifth intervention year. Substantial reductions in notified malaria cases were reported in South Africa and Swaziland over the same period. The success of the program in reducing malaria transmission throughout the target area provides a strong argument for investment in regional malaria control.", "The objective of this study was to produce data indicating whether insecticide-treated bednets should replace insecticide house spraying as a malaria control method in South Africa. We report 2 years of preliminary data on malaria incidence comparing areas receiving insecticide-treated bednets and those subjected to house spraying in northern KwaZulu-Natal.\n In order to measure significant reductions in malaria incidence between the two interventions, a geographical information system (GIS) was used to identify and create seven pairs of geographical blocks (areas) in the malaria high-risk areas of Ndumu and Makanis in Ingwavuma magisterial district, KwaZulu-Natal. Individual blocks were then randomly allocated to either insecticide-treated bednets or house spraying with deltamethrin. Malaria cases were either routinely recorded by surveillance agents at home or were reported to the nearest health facility.\n The results show that 2 years' use of insecticide-treated bednets by communities in Ndumu and Makanis, KwaZulu-Natal, significantly reduced the malaria incidence both in 1997 (rate ratio (RR) = 0.879, 95% confidence interval (CI) 0.80-0.95, P = 0.04) and in 1998 (RR = 0.667, CI 0.61-0.72, P = 0.0001). Using a t-test, these significant reductions were further confirmed by an assessment of the rate of change between 1996 and 1998, showing a 16% reduction in malaria incidence in blocks using treated bednets and an increase of 45% in sprayed areas (t = 2.534, P = 0.026 (12 df)). In order to decide whether bednets should replace house spraying in South Africa, we need more data on the efficacy of treated bednets, their long-term acceptability and the cost of the two interventions.", "In an intensely malarious area in north-east Tanzania, microencapsulated lambdacyhalothrin was used in four villages for treatment of bednets (provided free of charge) and in another four villages the same insecticide was used for house spraying. Another four villages received neither intervention until the end of the trial but were monitored as controls. Bioassays showed prolonged persistence of the insecticidal residues. Light traps and ELISA testing showed reduction of the malaria vector populations and the sporozoite rates, leading to a reduction of about 90% in the entomological inoculation rate as a result of each treatment. Collections of blood fed mosquitoes showed no diversion from biting humans to biting animals. Incidence of re-infection was measured by weekly monitoring of cohorts of 60 children per village, after clearing preexisting infection with chlorproguanil-dapsone. The vector control was associated with a reduction in probability of re-infection per child per week by 54-62%, with no significant difference between the two vector control methods. Cross-sectional surveys for fever, parasitaemia, haemoglobin and weight showed association of high parasitaemia with fever and anaemia and beneficial effects of each intervention in reducing anaemia. However, passive surveillance by resident health assistants showed no evidence for reduced prevalence of fever or parasitaemia. Net treatment consumed only about one sixth as much insecticide as house spraying and it was concluded that the former intervention would work out cheaper and nets were actively demanded by the villagers, whereas spraying was only passively assented to." ]

[ "21749629", "19489810", "9141576", "2321293", "11065032", "6388776", "8494832", "7819846", "3511958" ]

[ "Is the operative delivery rate in low-risk women dependent on the level of birth care? A randomised controlled trial.", "Re-conceptualizing the hospital labor room: the PLACE (pregnant and laboring in an ambient clinical environment) pilot trial.", "The Stockholm birth centre trial: maternal and infant outcome.", "[The significance of the environment for delivery at a special department].", "A randomised controlled trial comparing birthing centre care with delivery suite care in Adelaide, Australia.", "Care in a birth room versus a conventional setting: a controlled trial.", "Simulated home delivery in hospital: a randomised controlled trial.", "Midwife managed delivery unit: a randomised controlled comparison with consultant led care.", "The use of a birthroom: a randomized controlled trial comparing delivery with that in the labour ward." ]

[ "To investigate possible differences in operative delivery rate among low-risk women, randomised to an alongside midwifery-led unit or to standard obstetric units within the same hospital.\n Randomised controlled trial.\n Department of Obstetrics and Gynaecology, Østfold Hospital Trust, Tromsø, Norway.\n A total of 1111 women assessed to be at low risk at onset of spontaneous labour.\n Randomisation into one of three birth units: the special unit; the normal unit; or the midwife-led unit.\n Total operative delivery rate, augmentation, pain relief, postpartum haemorrhage, sphincter injuries and intrapartum transfer, Apgar score <7 at 5 minutes, metabolic acidosis and transfer to neonatal intensive care unit.\n There were no significant differences in total operative deliveries between the three units: 16.3% in the midwife-led unit; 18.0% in the normal unit; and 18.8% in the special unit. There were no significant differences in postpartum haemorrhage, sphincter injuries or in neonatal outcomes. There were statistically significant differences in augmentation (midwife-led unit versus normal unit RR 0.73, 95% CI 0.59-0.89; midwife-led unit versus special unit RR 0.69, 95% CI 0.56-0.86), in epidural analgesia (midwife-led unit versus normal unit RR 0.68, 95% CI 0.52-0.90; midwife-led unit versus special unit RR 0.64, 95% CI 0.47-0.86) and in acupuncture (midwife-led unit versus normal unit RR 1.45, 95% CI 1.25-1.69; midwife-led unit versus special unit RR 1.45, 95% CI 1.22-1.73).\n The level of birth care does not significantly affect the rate of operative deliveries in low-risk women without any expressed preference for level of birth care.\n © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.", "Nearly all hospitalized laboring women spend most of the time in bed. We made simple but radical modifications to a hospital labor room, which included the removal of the standard hospital bed and the addition of equipment to promote relaxation, mobility, and calm. We designed a pilot study, the objectives of which were to test the feasibility of a randomized trial and the acceptability of the modified labor room to women and their care providers.\n Women were assessed and invited to participate just before their admission to the labor and delivery suite. Sixty-two women at two Toronto teaching hospitals were randomly allocated to either the standard labor room or the \"ambient room.\" Data about labor and birth events were abstracted from the medical records. Participants and their nurses and physicians completed questionnaires to elicit their views of their experiences with the labor rooms.\n Women's and practitioners' evaluations of the ambient room were generally very positive. Nineteen women (65.5%) in the ambient group, compared with 4 (13.3%) in the standard group, reported spending 50 percent or less of their hospital labor in the standard labor bed. Twelve women allocated to the ambient room had artificial oxytocin infusions, compared with 21 allocated to the standard room (X (2) = 4.73, p = 0.03).\n We conclude that the ambient labor room should be evaluated in an adequately powered randomized controlled trial.", "To compare an in-hospital birth centre with standard maternity care regarding medical interventions and maternal and infant outcome.\n The birth centre care was characterised by comprehensive antenatal, intrapartum and postpartum care with the same team of midwives, restricted use of medical technology, and discharge within 24 h after birth.\n Of 1860 women meeting low risk medical criteria in early pregnancy and interested in birth centre care, 928 were randomly allotted birth centre care and 932 standard maternity care. Data were collected mainly from hospital records, and analysis was by intention-to-treat.\n Of the women in the birth centre group, 13% were transferred antenatally and 19% intrapartum. No statistical differences were observed in maternal morbidity or in perinatal mortality, neonatal morbidity, Apgar score or infant admissions to neonatal care. Perinatal mortality, defined as intrauterine death after 22 weeks of gestation and infant death within seven days of birth, occurred in eight cases (0.9%) in the birth centre group and in two cases (0.2%) in the standard care group (OR 4.04, 95% CI 0.80 to 39.17; P = 0.11). Subgroup analysis showed that a larger proportion of first-born babies in the birth centre group (15.6%) were admitted for neonatal care than in the standard care group (9.5%) (P = 0.003), whereas the converse was the case for the newborns of multiparous women: 4.7% and 8.4%, respectively (P = 0.04). The overall rates of operative delivery (e.g. caesarean section, vacuum extraction and forceps), 11.1% in the birth centre group and 13.4% in the standard care group, did not differ statistically (P = 0.12), but obstetric analgesia, induction, augmentation of labour and electronic fetal monitoring were less frequently used in the birth centre group. Labour was 1 h longer in the birth centre group.\n Birth centre care was associated with less medical interventions than standard care without any statistically significant differences in health outcomes. However, the excess of perinatal deaths and of morbidity in primigravidas' infants in the birth centre group gives cause for concern and necessitates further studies.", "A material of 292 normal pregnant women was subdivided at random for delivery either in the traditional delivery room or a newly established environmental room. The alterations in the physical environment of delivery did not result in more numerous spontaneous deliveries. A high frequency of episiotomies, stimulation of contractions and artificial deliveries in primiparae occurred particularly when it is considered that two thoroughly investigated groups of low-risk pregnant women were concerned. However, qualitative differences in the experience of the course of delivery were found in favour of the environmental room. The quality of the experience of delivery did not depend so much on the physical environment but more on contact with the staff members responsible for conduct of the delivery.", "Birthing centre care offers women with a low risk of complication in pregnancy an alternative to conventional care for the birthing of their baby. It is important these two forms of care are appropriately assessed. A randomised controlled trial comparing the newly opened birthing centre with the established conventional delivery suite was conducted at the then Queen Victoria Hospital, Adelaide, South Australia. The outcomes measured included maternal satisfaction, costs and clinical outcomes both for mother and baby which related to the need for Caesarean section, episiotomy or tear rate and method of feeding. Two hundred and one women attending the hospital's antenatal clinic were randomly allocated to either birthing centre or delivery suite care. One hundred women were allocated to the birthing centre. No differences were found in either group related to clinical outcomes or costs. The only difference in maternal satisfaction was the choice women made for their next birth. More women in the birthing centre group felt they were encouraged to breastfeed immediately after birth. While the numbers in this study were too small to detect any but large differences in outcome, birthing centre care should remain an option for women and further studies undertaken with larger numbers.", "A controlled clinical trial was carried out to assess whether a birth room setting would influence the care of mothers and newborns. Of the 163 low-risk women enrolled, 49 (30%) manifested some prenatal risk and were excluded. The remaining 114 were allocated by strict alternation to a birth room or a conventional setting. Of the 56 women allocated to the birth room, 63% of the primiparas and 19% of the multiparas were later transferred. The numbers in the two settings who had oxytocin stimulation, epidural anesthesia, forceps delivery or cesarean section did not show statistically significant differences. The episiotomy rates were slightly lower in the birth room than in the conventional setting, and the rates of an intact perineum were higher in the birth room. Neither the Apgar scores nor the morbidity rates of the infants showed statistically significant differences related to the setting to which the mother had been allocated, although more infants from the conventional setting were admitted to a special care unit. Both \"experimental\" groups of women less often received routine perineal shaving, enemas or intravenous infusions than did an obstetrically similar nonexperimental comparison group. Despite the apparent inability in this setting for the birth room to influence the rate of major obstetric procedures (except for episiotomy) and outcomes, the authors believe that a birth room is desirable in tertiary care centres as well as in community hospitals.", "To compare the outcome of two methods of maternity care during the antenatal period and at delivery. One was to be midwife-led for both antenatal care and delivery, the latter taking place in rooms similar to those in one's own home to simulate home confinement. The other would be consultant-led with the mothers labouring in the delivery suite rooms with resuscitation equipment for both mother and baby in evidence, monitors present and a delivery bed on which both anaesthetic and obstetric procedures could be easily and safely carried out.\n Randomised controlled trial.\n Leicester Royal Infirmary Maternity Hospital.\n Of 3510 women who were randomised, 2304 were assigned to the midwife-led scheme and 1206 were assigned to the consultant-led scheme.\n Complications in the antenatal, intrapartum and postpartum periods were compared as was maternal morbidity and fetal mortality and morbidity. Satisfaction of the women with care over different periods of the pregnancy and birth were assessed.\n There were few significant differences in antepartum, intrapartum and postpartum events between the two groups. There was no difference in the percentage of mothers and babies discharged home alive and well. Generally higher levels of satisfaction with care antenatally and during labour and delivery were shown in those women allocated to midwife care.", "To examine whether intrapartum care and delivery of low risk women in a midwife managed delivery unit differs from that in a consultant led labour ward.\n Pragmatic randomised controlled trial. Subjects were randomised in a 2:1 ratio between the midwives unit and the labour ward.\n Aberdeen Maternity Hospital, Grampian.\n 2844 low risk women, as defined by existing booking criteria for general practitioner units in Grampian. 1900 women were randomised to the midwives unit and 944 to the labour ward.\n Maternal and perinatal morbidity.\n Of the women randomised to the midwives unit, 647 (34%) were transferred to the labour ward antepartum, 303 (16%) were transferred intrapartum, and 80 (4%) were lost to follow up. 870 women (46%) were delivered in the midwives unit. Primigravid women (255/596, 43%) were significantly more likely to be transferred intrapartum than multi-gravid women (48/577, 8%). Significant differences between the midwives unit and labour ward were found in monitoring, fetal distress, analgesia, mobility, and use of episiotomy. There were no significant differences in mode of delivery or fetal outcome.\n Midwife managed intrapartum care for low risk women results in more mobility and less intervention with no increase in neonatal morbidity. However, the high rate of transfer shows that antenatal criteria are unable to determine who will remain at low risk throughout pregnancy and labour.", "A randomized controlled trial of two environments for delivery was conducted at Queen Charlotte's Maternity Hospital. A total of 253 parous women expecting to have a labour ward delivery were invited to participate in the trial but only 148 agreed. These women were randomly allocated to be delivered either with standard labour ward management (n = 72) or in the birthroom--a small bedroom decorated in a homely manner, without facilities for epidural analgesia or electronic fetal monitoring (n = 76). Eleven women in the birthroom group and 10 in the labour ward group withdrew from the trial before labour and four were transferred from the birthroom to the labour ward when in labour. A questionnaire sent in the postnatal period to the women who completed the trial was returned by 80%. In the birthroom group there was significantly (i) decreased admission-to-delivery interval (ii) less analgesia (iii) more freedom of movement (iv) less suturing (v) increased rooming-in. No difference was found in the assessment of difficulty of labour nor in the method of subsequent infant feeding." ]

[ "20008425", "11202662" ]

[ "Effect of domperidone on the composition of preterm human breast milk.", "Effect of domperidone on milk production in mothers of premature newborns: a randomized, double-blind, placebo-controlled trial." ]

[ "Domperidone is increasingly prescribed to improve breast milk volume despite a lack of evidence regarding its effects on breast milk composition. We examined the effect of domperidone on the nutrient composition of breast milk.\n Forty-six mothers who had delivered infants at <31 weeks' gestation, who experienced lactation failure, were randomly assigned to receive domperidone or placebo for 14 days. Protein, energy, fat, carbohydrate, sodium, calcium, and phosphate levels in breast milk were measured on days 0, 4, 7, and 14, serum prolactin levels were measured on days 0, 4, and 14, and total milk volume was recorded daily. Mean within-subject changes in nutrients and milk volumes were examined.\n Maternal and infant characteristics, serum prolactin level, and breast milk volume and composition were not significantly different between domperidone and placebo groups on day 0. By day 14, breast milk volumes increased by 267% in the domperidone-treated group and by 18.5% in the placebo group (P = .005). Serum prolactin increased by 97% in the domperidone group and by 17% in the placebo group (P = .07). Mean breast milk protein declined by 9.6% in the domperidone group and increased by 3.6% in the placebo group (P = .16). Changes in energy, fat, carbohydrate, sodium, and phosphate content were also not significantly different between groups. Significant increases were observed in breast milk carbohydrate (2.7% vs -2.7%; P = .05) and calcium (61.8% vs -4.4%; P = .001) in the domperidone versus placebo groups. No significant adverse events were observed among mothers or infants.\n Domperidone increases the volume of breast milk of preterm mothers experiencing lactation failure, without substantially altering the nutrient composition.", "Varying degrees of success have been reported with strategies to increase milk production when lactation is failing. The objective of this study was to investigate the efficacy of domperidone in augmenting milk production in mothers of premature newborns.\n Twenty patients were randomly assigned to receive either domperidone or placebo for 7 days. Milk volume was measured daily. Domperidone levels were measured in randomly selected milk and serum samples on day 5 of the study. Serum prolactin levels were measured before the start of the study, on day 5 and on day 10 (3 days after the last dose of the study medication).\n Data from 16 patients were available for analysis (7 in the domperidone group and 9 in the placebo group). When compared with baseline values, the mean increase in the volume of milk production from day 2 to 7 was 49.5 (standard deviation [SD] 29.4) mL in the domperidone group and 8.0 (SD 39.5) mL in the placebo group (p < 0.05); proportionally this represented an increase of 44.5% and 16.6% respectively. The serum prolactin levels were similar in the 2 groups at baseline; by day 5 they were significantly higher in the domperidone group than in the placebo group, returning to baseline levels in both groups 3 days after the last dose of the study medication. Very small amounts of domperidone were detected in the breast milk samples.\n In the short term domperidone increases milk production in women with low milk supply and is detected at low levels in breast milk." ]

[ "20090438", "14769578", "7772440", "17870625", "12766657", "19013751", "11309007", "18245999", "9783947", "20117910", "21692253", "16244006", "11772793", "16192774", "7917733", "17525598", "8876577", "16931684", "11154366", "18279623" ]

[ "Intraperitoneal lidocaine instillation and postcesarean pain after parietal peritoneal closure: a randomized double blind placebo-controlled trial.", "Comparison of spinal vs general anesthesia via laryngeal mask airway in inguinal hernia repair.", "Intra-vas deferens bupivacaine for prevention of acute pain and chronic discomfort after vasectomy.", "Comparison of epidural analgesia and intercostal nerve cryoanalgesia for post-thoracotomy pain control.", "Postoperative morphine use and hyperalgesia are reduced by preoperative but not intraoperative epidural analgesia: implications for preemptive analgesia and the prevention of central sensitization.", "[Ropivacaine infiltration during breast cancer surgery: postoperative acute and chronic pain effect].", "A bilateral clinical model for the study of acute and chronic pain after breast-reduction surgery.", "A prospective, randomized, double-blind study of the efficacy of postoperative continuous local anesthetic infusion at the iliac crest bone graft site after posterior spinal arthrodesis: a minimum of 4-year follow-up.", "Pain and quality of life following radical retropubic prostatectomy.", "[Efficiency of bupivacaine wound subfasciale infiltration in reduction of postoperative pain after inguinal hernia surgery].", "[Chronic postoperative pain after general anesthesia with or without a single-dose preincisional paravertebral nerve block in radical breast cancer surgery].", "Multimodal analgesia with gabapentin and local anesthetics prevents acute and chronic pain after breast surgery for cancer.", "The effects of three different analgesia techniques on long-term postthoracotomy pain.", "Intraoperative epidural analgesia combined with ketamine provides effective preventive analgesia in patients undergoing major digestive surgery.", "Multimodal analgesia before thoracic surgery does not reduce postoperative pain.", "Postoperative analgesic effects of continuous wound infiltration with diclofenac after elective cesarean delivery.", "Continuous postoperative infusion of a regional anesthetic after an amputation of the lower extremity. A randomized clinical trial.", "Preincisional paravertebral block reduces the prevalence of chronic pain after breast surgery.", "Digitally assisted acromioplasty: the effect of interscalene block on this new surgical technique.", "[Correlation of acute pain treatment to occurrence of chronic pain in tumor patients after thoracotomy]." ]

[ "To evaluate the effects of intraperitoneal instillation of lidocaine on postcesarean pain in patients with pariental periotoneal closure.\n A sample of 370 pregnant women, presenting early in labor, with no history of abdominal surgery and with indications for cesarean section were operated on with closure of the parietal peritoneum. They randomly received either 200 mg of intraperitoneal lidocaine or sterile saline (0.9%). Pain scores on the first and fifteenth postoperative days were recorded and followed up every 2 weeks up to 8 months after surgery.\n Overall incidence and pain scores of epigastric and global abdominal pain were more frequent in the controls than in the lidocaine group. The incidence of persistent postcesarean pain after 8 months dropped from 20.8.0% to 10.8% (P<0.001) when intraperitoneal lidocaine was instilled.\n Intraperitoneal instillation of 200 mg of lidocaine decreased the incidence and scores of postcesarean pain when the parietal peritoneum was sutured. Further studies in a setting offering more effective acute pain control protocols, preferably with patient-controlled analgesia, are recommended to assess the use of lidocaine before it can be widely practiced.", "The use of laryngeal mask airway and propofol in inguinal hernia repair results in shorter operative and recovery room times.\n Randomized control trial.\n University hospital.\n From May 2000 to March 2002, a convenience sample of 79 patients was invited to participate; 34 entered the study. Fifteen patients were randomized to subarachnoid block, and 18 patients were randomized to laryngeal mask airway. No patients withdrew from the study because of adverse effects. All study subjects were followed up for 6 months.\n General anesthesia via laryngeal mask airway or lidocaine subarachnoid block anesthesia for inguinal hernia repair.\n Operative and recovery room times; surgeon evaluation of the adequacy of the anesthetic technique; 36-Item Short-Form Health Survey scores before and after operation.\n Total time from entry into the operating room to discharge home was slightly longer in the subarachnoid block group (285 vs 262 minutes; 95% confidence interval, 251-317 minutes) but this difference was not statistically or clinically significant. Patient satisfaction was high with both techniques; patient-reported outcomes were the same. Surgeons rated muscle relaxation and exposure better with the subarachnoid block.\n We found no differences between short-acting spinal anesthesia and general anesthesia via laryngeal mask airway with intravenous propofol in efficiency or in early or late outcomes after elective inguinal hernia repair. Surgeon and patient preferences appear to be the most important reasons for selecting an anesthetic technique for individual patients undergoing inguinal hernia repair.", "We have studied the use of intra-vas deferens local anaesthesia in 70 patients undergoing vasectomy as day-case patients. Patients were allocated randomly to either a control or treatment group. In the treatment group, 0.5% bupivacaine 1 ml or 0.9% saline 1 ml was injected into the lumen of the right or left vas deferens in a randomized blinded design. The control group did not receive an injection. Patients were discharged with a questionnaire for recording visual analogue scores (VAS) for both the right and left sides to be scored on days 1 and 7 after operation. One year after the procedure a second questionnaire was sent out asking about the presence or absence of chronic testicular discomfort, its duration and any surgical intervention required to relieve it. There were no differences between the control group and the saline side of the treatment group in VAS scores on both day 1 and day 7 after operation or in the incidence and duration of chronic testicular discomfort (mean 30 (SD 53) and 34 (50) days, respectively). The VAS scores were, however, significantly less (P < 0.005) and testicular discomfort was absent on the bupivacaine-treated side.", "Epidural analgesia is regarded as the gold method for controlling post-thoracotomy pain. Intercostal nerve cryoanalgesia can also produce satisfactory analgesic effects, but is suspected to increase the incidence of chronic pain. However, randomized controlled trials comparing these two methods for post-thoracotomy acute pain analgesic effects and chronic pain incidents have not been conducted previously. We studied 107 adult patients, allocated randomly to thoracic epidural bupivacaine and morphine or intercostal nerve cryoanalgesia. Acute pain scores and opioid-related side effects were evaluated for three postoperative days. Chronic pain information, including the incidence, severity, and allodynia-like pain, was acquired on the first, third, sixth and twelfth months postoperatively. There was no significant difference on numeral rating scales (NRS) at rest or on motion between the two groups during the three postoperative days. The patient satisfaction results were also similar between the groups. The side effects, especially mild pruritus, were reported more often in the epidural group. Both groups showed high incidence of chronic pain (42.1-72.1%), and no significance between the groups. The incidence of allodynia-like pain reported in cryo group was higher than that in Epidural group on any postoperative month, with significance on the sixth and the twelfth months postoperatively (P<0.05). More patients rated their chronic pain intensity on moderate and severe in cryo group and interfered with daily life (P<0.05). Both thoracic epidural analgesia and intercostal nerve cryoanalgesia showed satisfactory analgesia for post-thoracotomy acute pain. The incidence of post-thoracotomy chronic pain is high. Cryoanalgesia may be a factor that increases the incidence of neuropathic pain.", "The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control.\n Patients undergoing major gynecologic surgery by laparotomy were randomly assigned to three groups and studied in a double-blinded manner. Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision. Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision. Group 3 received a sham epidural control (with saline injected into a catheter taped to the back) before and 40 min after incision. All patients underwent surgery with general anesthesia.\n One hundred forty-one patients completed the study (group 1, n = 45; group 2, n = 49; group 3, n = 47). Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower (P = 0.04) in group 1 (89.8 +/- 43.3 mg) than group 3 (112.5 +/- 71.5 mg) but not group 2 (95.4 +/- 60.2 mg), although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower (P < 0.0009) in group 1 (1.25 +/- 0.02 mg/h) than group 2 (1.41 +/- 0.02 mg/h). Twenty-four hours after surgery, the visual analog scale pain score on movement was significantly less intense (P = 0.005) in group 1 (4.9 +/- 2.2 cm) than group 3 (6.0 +/- 2.6 cm) but not group 2 (5.3 +/- 2.5 cm), and the von Frey pain threshold near the wound was significantly higher (P = 0.03) in group 1 (6.4 +/- 0.6 log mg) than in group 3 (6.1 +/- 0.8 log mg) but not group 2 (6.2 +/- 0.7 log mg).\n Preincisional administration of epidural lidocaine and fentanyl was associated with a significantly lower rate of morphine use, lower cumulative morphine consumption, and reduced hyperalgesia compared with a sham epidural condition. These results highlight the importance of including a standard treatment control group to avoid the problems of interpretation that arise when two-group studies of preemptive analgesia (preincisional vs. postsurgery) fail to find the anticipated effects.", "Decrease acute pain after breast cancer surgery by an infiltration of ropivacaine. Analyse effect on chronic pain.\n Prospective randomised double blind versus placebo study.\n Eighty-one patients randomised between two groups received wound infiltration with 40 ml of ropivacaine 4.75 mg/ml or placebo. Acute pain was assessed during 24h with analogical visual scale and antalgic consumption. One year later, telephonic interviews looked for chronic pain and evaluate it with McGill Pain Questionnaire.\n Analogical visual scale pain score, antalgic consumption and chronic pain incidence were similar between groups.\n Ropivacaine scar infiltration provided no acute or chronic pain relief after breast cancer surgery.", "There is a need for new clinical models to investigate effectively the development of pain after surgery and the effect, if any, of pre-emptive treatment. Bilateral models are of special interest, since the patient serves as his/her own control. The objective of this preliminary study was to test a clinical model for the study of acute and chronic pain after bilateral reduction mammoplasty.\n Eight patients participated in the study where the breasts were randomized to test and control groups. In each patient, one breast was preoperatively infiltrated with lidocaine and adrenaline and the other breast infiltrated with saline and adrenaline. Assessment included visual analogue scale (VAS) pain intensity, thermal thresholds, mapping for punctate hyperalgesia and tactile sensation. Assessments were made preoperatively, postoperatively and at 6 months after surgery.\n With regard to acute postoperative pain intensity, the model demonstrated a clear difference between lidocaine and placebo treated breasts. There was no difference between lidocaine and placebo treated breasts with regard to chronic pain, but these results are inconclusive due to small number of patients.\n The model is sensitive and may be useful in studies of mechanisms of development and prevention of chronic pain after surgery.", "Parallel design, prospective, double-blinded, randomized, controlled trial composed of 2 independent groups treated with a continuous infusion catheter (saline vs. Marcain) placed into the iliac crest bone graft site (ICBG).\n To determine the long-term effects of postoperative continuous local anesthetic agent infusion at the ICBG harvest site in reducing chronic pain, narcotic usage and improving long-term, postoperative function and satisfaction with the surgical procedure.\n Harvesting iliac crest bone has been shown to be a source of pain and morbidity. In our initial study, we reported that patients who received local anesthetic at the graft site noted a reduction in acute postoperative pain (VAS) and narcotic usage. METHODS.: Twenty-six patients underwent posterior iliac crest bone graft harvesting. Patients were randomly assigned to receive 96 mL (2 mL/h x 48 hours) of either 0.5% Marcain or normal saline delivered via a continuous infusion catheter placed at the ICBG harvest site. Postoperative pain scores, narcotic use/frequency, activity level, and length of stay (LOS) were recorded and reported previously. At a minimum of 4 years after surgery (mean, 4.7 years; range, 4.5-5.4 years), all patients completed a questionnaire documenting their current VAS pain score (iliac crest), frequency of pain (days per month), level of activity, chronic pain at the ICBG site, and overall satisfaction with the procedure.\n Nine of 11 patients (82%) in the treatment group and 10 of 14 patients (71%) in the control group were available at final follow-up (1 death occurred in the control group unrelated to the study). The treatment group had a statistically significant decrease in the graft site pain VAS score (1.4 vs. 4.8) and increased satisfaction with the procedure at a minimum of 4 years postprocedure (P < 0.05). Additionally, no patient in the treatment group developed chronic iliac crest dysesthesias (0 of 9) versus 7 of 10 patients (70%) in the control group (P < 0.05).\n Continuous infusion of 0.5% Marcain at the ICBG harvest site significantly reduced chronic dysesthesias. Overall satisfaction with the procedure, number of painful days per month, and VAS scores were significantly better in the treatment group at 4 years. No long-term complications were attributed to either the ICBG site or the catheter-infusion system. The use of continuous local anesthetic infusion at the iliac crest may help in alleviating graft-related pain beyond the perioperative phase.", "We assess pain and quality of life following radical retropubic prostatectomy and determine whether intraoperative anesthetic management has any long-term effects on outcomes.\n A total of 110 patients undergoing radical retropubic prostatectomy were randomly assigned to receive epidural and/or general anesthesia. Patients responded to a questionnaire mailed 3 and 6 months following surgery that assessed prostate symptoms, pain related to surgery, quality of life and mood.\n No long-term effects of anesthesia were observed. Of the 103 respondents (94%) at 3 months 49% had some pain related to surgery. Although pain was not related to anesthesic technique, patients who had it at 3 months used significantly more pain medication on postoperative day 3. Pain at 3 months was mild, averaging 1.5 on a scale of 0 to 10, and associated with poor perceptions of overall health (p <0.02), and reduced physical (p <0.01) and social (p <0.01) functioning. Pain at 3 months was associated with higher levels of preoperative anxiety (p <0.05). At 6 months 36 of 90 patients (35%) had some pain related to surgery and the impact was similar.\n Long-term effects of intraoperative anesthesic technique were not apparent. Mild pain following radical retropubic prostatectomy was common and associated with reduced quality of life, particularly social functioning. Affective distress, particularly anxiety, before surgery and use of pain medications following surgery may be predictors of chronic pain following radical retropubic prostatectomy.", "The reduction of postoperative pain after surgery of inguinal hernia is an objective of lot of studies. The subfasciale infiltration of the wound may be an efficient technique.\n This study was designed as a randomized, double blind, prospective study, comparing two treatment groups: a group infiltrated by bupivacaine (Gr B), and second one infiltrated by a placebo (Gr P). A part of demographic parameters and ASA class, the postoperative pain intensity at rest and at coughing, the morphine consumption and the secondary effects were compared. Patient's satisfaction and postoperative chronic pain at 3 and 6 months were also analyzed.\n Concerning demographic parameters, ASA class and secondary effects, we didn't find any meaningful difference between the two groups. However, there was a significant reduction of postoperative pain in the bupivacaine group as well at rest as coughing. Gr P patients have more morphine consumption and they were unsatisfied and accused more chronic pain.\n Wound infiltration is still a simple and efficient technique in postoperative pain reduction. With this technique, hernia surgery may become ambulatory.\n Copyright 2009 Elsevier Masson SAS. All rights reserved.", "Over 50% of patients still experience pain a year after mastectomy with or without lymphadenectomy. We aimed to determine the association between anesthetic technique, acute postoperative pain intensity, and the development of chronic postoperative pain. Patients and\n Forty patients were randomly assigned to receive general anesthesia with or without a paravertebral nerve block for modified radical mastectomy. Postoperative pain was assessed on a visual analog scale at 60 minutes and 24 hours; the patients were also asked to respond to a telephone questionnaire on chronic pain 4 to 5 months later.\n No significant differences in acute pain were observed. Twenty-nine responded to the telephone questionnaire. Only 1 patient in the paravertebral block group reported chronic neuropathic pain and none had phantom breast pain. Only 1 patient (6.7%) in the paravertebral block group reported chronic neuropathic pain and none had phantom breast pain. In the group that received general anesthesia alone, 1 patient reported phantom breast pain and 6 patients had neuropathic pain, associated with phantom breast pain in 2 cases (incidence of chronic pain 50%; P = .01, Fischer exact test; relative risk, 7.5, 95% confidence interval, 1.0-53.5). The incidences of myofascial pain (neck muscle tightness) were similar in the 2 groups.\n Four to 5 months after mastectomy, fewer cases of chronic pain developed in the group operated under general anesthesia with a preincisional paravertebral block than in the group that received only general anesthesia, with postoperative morphine chloride for analgesia.", "We evaluated the effect of multimodal analgesia on acute and chronic pain after breast surgery for cancer. Fifty patients scheduled for breast cancer surgery were blindly randomized to receive gabapentin, eutectic mixture of local anesthetics cream, and ropivacaine in the wound or three placebos. Pain (visual analog scale) and analgesics were recorded in the postanesthesia care unit (PACU) 3, 6, and 9 h and 8 days after surgery. Three and 6 mo later, patients were assessed for chronic pain. The treatment group consumed less paracetamol in the PACU (469 versus 991 mg; P < 0.002) and less Lonalgal (1.0 versus 4.4 tablets; P = 0.003) than the controls, exhibited lower visual analog scale scores at rest in the PACU (P = 0.001) and on postoperative Days 1, 3, and 5 (P = 0.040, P = 0.015, and P = 0.045, respectively), and after movement in the PACU (P = 0.001) and on postoperative Days 2, 4, and 8 (P = 0.028, P = 0.007, and P = 0.032, respectively). Three and 6 mo after surgery, 18 of 22 (82%) and 12 of 21 (57%) of the controls reported chronic pain versus 10 of 22 (45%) and 6 of 20 (30%) in the treatment group (P = 0.028 and P = 0.424, respectively); 5 of 22 and 4 of 21 of the controls required analgesics versus 0 of 22 and 0 of 20 of those treated (P = 0.048 and P = 0.107, respectively). Multimodal analgesia reduced acute and chronic pain after breast surgery for cancer.", "In this clinical, randomized, prospective study, we compared the effects of three different analgesia techniques (thoracic epidural analgesia [TEA] with and without preoperative initiation and IV patient-controlled analgesia [IV-PCA]) on postthoracotomy pain in 69 patients. In two groups, a thoracic epidural catheter was inserted preoperatively. Group Pre-TEA had bupivacaine and morphine solution preoperatively and intraoperatively. Postoperative analgesia was maintained with epidural PCA with a similar solution. Group Post-TEA, with no intraoperative medication, had the same postoperative analgesia as Group Pre-TEA plus the bolus dose. Group IV-PCA received only IV-PCA with morphine for postoperative analgesia. Pain was evaluated every 4 h during the first 48 h at rest, cough, and movement. Pre-TEA was associated with decreased pain compared with the other groups. Six months later, the patients were asked about their pain. The incidence and the intensity of pain were most frequent in Group IV-PCA (78%) and were the least in Group Pre-TEA (45%) (Group Pre-TEA versus Group IV-PCA, P = 0.0233; Group Pre-TEA versus Group IV-PCA, P = 0.014). Patients having pain on the second postoperative day had 83% chronic pain. TEA with preoperative initiation is a preferable method in preventing acute and long-term thoracotomy pain.\n Preoperatively initiated thoracic epidural analgesia has the most satisfying results in controlling postthoracotomy pain in the acute and long-term period, and it is associated with a decreased incidence (and intensity) of chronic pain compared with postoperative (epidural or IV) analgesia. Chronic pain has an incidence of 62%.", "As a broader definition of preemptive analgesia, preventive analgesia aims to prevent the sensitization of central nervous system, hence the development of pathologic pain after tissular injury. To demonstrate benefits from preventive treatment, objective measurement of postoperative pain such as wound hyperalgesia and persistent pain should be evaluated. The current study assessed the role and timing of epidural analgesia in this context.\n In a randomized, double-blinded trial, 85 patients scheduled to undergo neoplastic colonic resection were included. All the patients received a thoracic epidural catheter, systemic ketamine at a antihyperalgesic dose, and general anesthesia. Continuous infusion of analgesics belonging to the same class was administered by either intravenous or epidural route before incision until 72 h after surgery. Patients were allocated to four groups to receive intraoperative intravenous lidocaine-sufentanil-clonidine or epidural bupivacaine-sufentanil-clonidine followed postoperatively by either intravenous (lidocaine-morphine-clonidine) or epidural (bupivacaine-sufentanil-clonidine) patient-controlled analgesia. Postoperative pain scores (visual analog scale), analgesic consumption, wound area of punctuate hyperalgesia, residual pain, and analgesics needed from 2 weeks until 12 months were recorded.\n Analgesic requirements, visual analog scale scores, and area of hyperalgesia were significantly higher in the intravenous treatment group (intravenous-intravenous), and more patients reported residual pain from 2 weeks until 1 yr (28%). Although postoperative pain measurements did not differ, postoperative epidural treatment (intravenous-epidural) was less effective to prevent residual pain at 1 yr (11%; P = 0.2 with intravenous-intravenous group) than intraoperative one (epidural-epidural and epidural-intravenous groups) (0%; P = 0.01 with intravenous-intravenous group).\n Combined with an antihyperalgesic dose of ketamine, intraoperative epidural analgesia provides effective preventive analgesia after major digestive surgery.", "Several reports have suggested that preoperative nociceptive block may reduce postoperative pain, analgesic requirements, or both, beyond the anticipated duration of action of the analgesic agents. We have investigated, in a double-blind, placebo-controlled study, pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen. Thirty patients undergoing thoracotomy were allocated randomly to two groups. Before surgery, the treatment group (n = 15) received morphine 0.15 mg kg-1 i.m. with perphenazine 0.03 mg kg-1 i.m. and a rectal suppository of indomethacin 100 mg, while the placebo group (n = 15) received midazolam 0.05 mg kg-1 i.m. and a placebo rectal suppository. After induction of anaesthesia, the treatment group received intercostal nerve block with 0.5% bupivacaine and adrenaline 1:200,000 (3 ml) in the interspace of the incision and in the two spaces above and two spaces below. The placebo group received identical injections but with normal saline only. The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation, but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group. There were no differences between the groups in postoperative VAS scores (at rest or after movement), PaCO2 values or postoperative spirometry. However, pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups. The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain.", "Postoperative pain mostly results from sensitization of afferent fibers at injury sites driving central sensitization. Recently, peripheral processes have gained attention as mechanisms of hyperalgesia, and prostaglandins are among highly sensitizing agents. To date, perioperative administration of a single local dose of nonsteroidal antiinflammatory drugs has shown inconclusive efficacy. Rather than a single bolus, the current study evaluates the postoperative analgesic effect of diclofenac continuous intrawound infusion after elective cesarean delivery.\n Ninety-two parturients were randomly allocated to receive a 48-h continuous intrawound infusion with 240 ml containing 300 mg diclofenac, 0.2% ropivacaine, or saline. In the ropivacaine and saline groups, patients also received 75 mg intravenous diclofenac every 12 h for 48 h. Postoperative evaluation included intravenous morphine consumption by patient-controlled analgesia and visual analog pain scores. Punctate mechanical hyperalgesia surrounding the wound and presence of residual pain after 1 and 6 months were also assessed.\n Continuous diclofenac infusion significantly reduced postoperative morphine consumption (18 mg; 95% confidence interval, 12.7-22.2) in comparison with saline infusion and systemic diclofenac (38 mg; 95% confidence interval, 28.8-43.7) (P=0.0009) without unique adverse effects. Postoperative analgesia produced by local diclofenac infusion was as effective as local ropivacaine infusion with systemic diclofenac.\n After elective cesarean delivery, continuous intrawound infusion of diclofenac demonstrates a greater opioid-sparing effect and better postoperative analgesia than the same dose administered as an intermittent intravenous bolus.", "We performed a prospective, randomized clinical trial to determine whether continuous infusion of bupivacaine hydrochloride decreased the use of narcotics for the relief of pain after an amputation. Twenty-one patients who were to have an amputation of the lower extremity because of ischemic necrosis secondary to peripheral vascular disease were divided into two groups with use of a table of random numbers. Group A (the treatment group) included nine patients who were to have a transtibial amputation, one patient who was to have a disarticulation at the knee, and one patient who was to have a transfemoral amputation. Group B (the control group) included seven patients, two patients, and one patient, respectively. After the amputation had been performed, a Teflon catheter was placed adjacent to the transected end of the sciatic or posterior tibial nerve. Postoperatively, the patients received continuous infusion of either bupivacaine (Group A) or normal saline solution (Group B) for seventy-two hours. Intravenous administration of morphine with use of a patient-controlled pump also was permitted during this period. The amount of morphine that was used was recorded meticulously. The patients in Group A used less morphine during the first and second days after the operation than did those in Group B. There was no difference between the groups with regard to the amount of morphine used on the third postoperative day. Over-all, eleven of fourteen patients who completed questionnaires reported a decrease in pain between the three and six-month evaluations. We concluded that continuous perineural infusion of an anesthetic appears to be a safe, effective method for the relief of postoperative pain but that it does not prevent residual or phantom-limb pain in patients who have had an amputation of the lower extremity because of ischemic changes secondary to peripheral vascular disease.", "We reported earlier that preincisional paravertebral block (PVB) provides significant immediate postoperative analgesia after breast cancer surgery. In the same patients (n = 60), a 1-yr follow-up was performed to find out whether PVB could also reduce the prevalence of postoperative chronic pain. The follow-up consisted of a 14-day symptom diary and telephone interviews 1, 6, and 12 mo after surgery. The 14-day consumption of analgesics was similar in the 30 PVB and the 30 control patients. However, 1 mo after surgery, the intensity of motion-related pain was lower (P = 0.005) in the PVB group. Six months after surgery, the prevalence of any pain symptoms (P = 0.029) was lower in the PVB group. Finally, at 12 mo after surgery, in addition to the prevalence of pain symptoms (P = 0.003) and the intensity of motion-related pain (P = 0.003), the intensity of pain at rest (P = 0.011) was lower in the PVB group. These findings were independent of whether or not axillary dissection had been performed. The incidence of neuropathic pain was low (two and three patients in the PVB and control groups, respectively). In addition to providing acute postoperative pain relief, preoperative PVB seems to reduce the prevalence of chronic pain 1 yr after breast cancer surgery.", "Interscalene brachial plexus (ISBP) block has been shown to be safe and effective for shoulder surgery with significant benefits. The purpose of this study was to introduce the technique of digitally assisted acromioplasty and assess the effect of ISBP on rehabilitation.\n Randomized controlled prospective trial.\n In a randomized prospective trial of 40 patients undergoing acromioplasty under general anesthesia, 20 patients received an ISBP block (group 1) and 20 had no block (group 2). A digitally assisted acromioplasty was performed using a burr introduced via a posterior portal. The undersurface of the acromion was debrided, directing the burr with the surgeon's index finger introduced via a small lateral incision. Independent review was at day 1, day 2, week 1, week 6, and 1 year.\n Group 1 had significantly greater shoulder motion and shoulder score, and less pain and analgesic requirements on the first day. These differences did not persist. Both groups had improved pain and function over time compared with preoperative scores.\n ISBP provides superior initial results but does not offer any significant persistent functional or rehabilitative advantage in the medium to long term. Digitally assisted acromioplasty is simple to perform and does not violate the deltoid insertion.", "Some researches found that the intensity, property and management of acute pain are associated with chronic pain in tumor patients after thoracotomy. Chronic pain may be transformed from acute pain. However, there are no routine or standard strategies to effectively prevent or relieve chronic pain in tumor patients after thoracotomy. This study was to explore the correlation of acute and chronic pain in tumor patients after thoracotomy.\n A total of 105 patients (American Society of Anesthesiologists physical status I-II) underwent thoracotomy were randomly divided into 3 groups: 36 received administration of ropivacaine and morphine through thoracic epidural preoperatively (group PE), 36 received the same treatment postoperatively (group E), and 33 received intravenous infusion of fentanyl postoperatively (group IV). VAS scores were recorded in the first 48 h after operation. The occurrence of chronic pain was observed at the first, second, third, sixth months after operation.\n VAS scores in the first 48h after operation were significantly lower in group PE and group E than that in group IV (P<0.05). VAS scores were significantly lower in group PE than in group E (P=0.004 at 4 h, P=0.013 at 8 h, P=0.035 at 24 h). The occurrence rate of pain after operation was significantly lower in group PE than in groups E and IV in the first and second months (Chi2=5.989, P=0.014; Chi2=7.603, P=0.006), and lower in groups PE and E than in group IV in the third and sixth months (Chi2=6.585, P=0.010; Chi2=8.661, P=0.003). The duration of pain was significantly shorter in group PE than in groups E and IV (P=0.027, P=0.009).\n Chronic pain after thoracotomy is associated with the intensity and management of acute pain after thoracotomy. The patients with intensive acute pain would experience intensive and long-term chronic pain. Preemptive administration with thoracic epidural ropivacaine and morphine can decrease the incidence and duration of chronic pain after operation." ]

[ "16182685", "8460615", "16467348" ]

[ "Failure of conventional strategies to improve nutritional status in malnourished adolescents and adults with cystic fibrosis.", "Relationships among nutritional status and skeletal and respiratory muscle function in cystic fibrosis: does early dietary supplementation make a difference?", "Oral protein energy supplements for children with cystic fibrosis: CALICO multicentre randomised controlled trial." ]

[ "The use of oral dietary supplements was compared with dietary counseling in 13 malnourished patients (3 males, mean age 18.1 years) with cystic fibrosis. Energy intake and nutritional status were evaluated over 3 months. There was no significant change in energy intake or percent ideal body weight in either group.", "Relationships among nutritional status and skeletal and respiratory muscle function were examined in 16 children with cystic fibrosis (CF) and mild lung disease (FEV1 95 +/- 16% predicted). Subjects were randomly assigned to receive (or not) noninvasive nutritional supplementation at 25% of normal energy recommendations for 6 mo. Skeletal muscle strength and power were similar to those of healthy children as were respiratory muscle strength and endurance. Stepwise-regression analysis indicated that changes in skeletal muscle strength and energy intake correlated significantly with growth [weight (kg) = 1.90 - 0.60 (Tanner Stage) + 0.49 (maximum voluntary strength (Nm) + 0.03 (energy intake, % RNI), r = 0.76, P < 0.05], though body composition, protein biochemistry, muscle power, respiratory muscle strength, and use of dietary supplements did not. Thus, changes in skeletal muscle strength may be a functional index of changes in nutritional status in CF. Dietary supplementation per se was not associated with functional improvement.", "To determine whether oral protein energy supplements, used long term in children with cystic fibrosis who are moderately malnourished, improve nutritional and other outcomes.\n Multicentre randomised controlled trial.\n Seven specialist paediatric cystic fibrosis centres and their associated shared care clinics and seven smaller paediatric cystic fibrosis clinics.\n 102 children with cystic fibrosis, aged between 2 and 15 years, who were moderately malnourished.\n Oral protein energy supplements in addition to usual dietary advice compared with dietary advice alone, for 12 months.\n Change in body mass index centile over one year.\n Use of supplements was not associated with a change in body mass index centile (mean difference 2.99 centile points, 95% confidence interval -2.70 to 8.68) or other nutritional and spirometric outcomes in this group of children.\n Long term use of oral protein energy supplements did not result in an improvement in nutritional status or other clinical outcomes in children with cystic fibrosis who were moderately malnourished. Oral protein energy supplements should not be regarded as an essential part of the management of this group of children.\n ISRCTN: 95744468." ]

[ "10636157", "9521250", "9222182", "12451199", "16510768", "17652642", "17721095", "9674806", "10430432", "16877299" ]

[ "Transdermal selegiline in HIV-associated cognitive impairment: pilot, placebo-controlled study.", "A randomized, double-blind, placebo-controlled trial of deprenyl and thioctic acid in human immunodeficiency virus-associated cognitive impairment. Dana Consortium on the Therapy of HIV Dementia and Related Cognitive Disorders.", "Safety and tolerability of the antioxidant OPC-14117 in HIV-associated cognitive impairment. The Dana Consortium on the Therapy of HIV Dementia and Related Cognitive Disorders.", "A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment.", "Valproic acid adjunctive therapy for HIV-associated cognitive impairment: a first report.", "A multicenter trial of selegiline transdermal system for HIV-associated cognitive impairment.", "Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study.", "A phase I/II trial of nimodipine for HIV-related neurologic complications.", "Randomized trial of the platelet-activating factor antagonist lexipafant in HIV-associated cognitive impairment. Neurological AIDS Research Consortium.", "Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of D-Ala1-peptide T-amide for HIV-1-associated cognitive-motor impairment." ]

[ "The authors conducted a pilot randomized, double-blind, placebo-controlled clinical trial of the transdermal administration of selegiline in HIV+ patients to obtain preliminary data to assess its safety, tolerability, and impact on HIV-associated cognitive impairment. Both selegiline and placebo were well tolerated with few adverse events. Improvements favoring the selegiline group were suggested on single tests of verbal memory and motor/psychomotor performance, warranting a larger study.", "Cognitive impairment is a frequent manifestation of advanced human immunodeficiency virus (HIV) infection. The response to antiretroviral medication is often partial and poorly sustained. Recent studies suggest that free radical production within the CNS and neuronal apoptosis may play important roles in the pathogenesis of HIV dementia. We conducted a randomized double-blind, placebo-controlled trial using a parallel group, 2 x 2 factorial design evaluating deprenyl, a monoamine oxidase B inhibitor and putative anti-apoptotic agent, and thioctic acid, an antioxidant, in 36 patients with HIV-associated cognitive impairment. Both deprenyl and thioctic acid were well tolerated with few adverse events. Deprenyl recipients showed significant improvement on tests of verbal memory compared with patients not taking deprenyl. Thioctic acid treatment did not improve cognitive function. These results suggest that deprenyl treatment is associated with cognitive improvement in subjects with mild HIV-associated cognitive impairment, whereas thioctic acid has no benefit. A larger efficacy trial is needed to assess the long-term effect of deprenyl on cognitive performance in patients with HIV infection.", "Cognitive impairment is a common and disabling complication of advanced HIV infection. Antiretroviral agents are the only proven therapies currently used for the treatment of HIV dementia, but the response to these agents is frequently unsatisfactory, short-lived, or complicated by intolerable side effects. We hypothesized that OPC-14117, a lipophilic antioxidant that acts to scavenge superoxide anion radicals, might ameliorate the toxic interactions between HIV infected macrophages and neurons. We conducted a double-blind, placebo-controlled, randomized clinical trial to assess the safety and tolerability of OPC-14117 240 mg per day. All 30 patients enrolled (15 per group) had cognitive impairment based on performance on neuropsychological tests. The primary outcome was tolerability of the study drug as measured by the proportion of subjects able to complete the study on their assigned dosage of experimental medication. Overall OPC-14117 was as well tolerated as placebo. Five subjects withdrew because of adverse experiences (two placebo, three OPC-14117). The OPC-14117-treated group had better scores on a clinical global impression scale, compared with the placebo group. There were trends toward improvement in the cognitive test scores; however, these changes were not statistically significant. These results demonstrate that this antioxidant intervention is well tolerated in cognitively impaired patients with advanced HIV infection, and suggest that a larger efficacy trial to assess the impact of OPC-14117 on cognitive performance is warranted.", "CPI-1189 is a compound with antioxidant properties that blocks tumor necrosis factor-alpha (TNFalpha) effects in animal models. It has neuroprotective properties in model systems for HIV-associated neurotoxicity and thus is a candidate for neuroprotective therapy in humans with HIV-associated CNS disease.\n To assess the tolerability and safety of CPI-1189 in treating HIV-associated cognitive-motor impairment.\n Sixty-four subjects with mild to moderate HIV-associated cognitive-motor impairment were randomized to receive either placebo or 50 or 100 mg daily of CPI-1189 in addition to optimal HIV therapy. Subjects were followed prospectively in a double-masked study for 10 weeks. The primary assessment was tolerability and safety of the compound. Secondary objectives examined neuropsychological and functional change associated with this treatment.\n The study compound was well tolerated, with 91% of CPI-1189-treated subjects and 76% of placebo-treated subjects completing the trial. Skin rash was seen equally in placebo and active arms, but the only study withdrawals due to skin rash occurred in CPI-1189-treated subjects (n = 2). One subject developed a cataract on drug (100 mg/day). CD4 lymphocyte counts and plasma HIV viral load remained stable in all groups throughout the trial. No significant treatment effects were observed on the change in composite Z-scores for eight neuropsychologic measures (NPZ-8). The Grooved Pegboard Test (nondominant) showed improved performance with CPI-1189 at 100 mg/day (p = 0.01), but no other neuropsychometric or functional measures demonstrated significant improvement.\n CPI-1189 was well tolerated in HIV subjects with cognitive-motor disorder. This study was not powered to conclusively determine efficacy and showed no consistent treatment-associated improvement in cognitive or functional measures.", "In vitro and animal model data demonstrate that valproic acid (VPA) can ameliorate HIV-associated neurotoxicity. The authors conducted a pilot 10-week placebo-controlled study of VPA 250 mg twice daily in 22 HIV-infected individuals with (n = 16) and without (n = 6) cognitive impairment. VPA was safe and well tolerated, with trends toward improved neuropsychological performance and brain metabolism in the impaired subjects.", "Cognitive impairment continues to be a significant neurologic complication of HIV infection and has been associated with oxidative stress-induced neuronal injury. Selegiline is an MAO-B inhibitor with antioxidant and neurotrophic properties. This rationale has led to the design and implementation of this Selegiline Transdermal System (STS) study with the primary aims of assessing safety and tolerability of STS as well as improvement in cognitive performance.\n HIV-1 infected individuals with impaired cognitive functioning were enrolled in this placebo-controlled, three-arm study of STS across 17 sites. Cognitive impairment was determined using a standard battery of neuropsychological tests. Subjects were randomized to receive STS 3 mg/24 hours, STS 6 mg/24 hours, or matching placebo patches daily. The primary efficacy endpoint was defined as the change in neuropsychological composite Z-score (NPZ-6) from baseline to week 24. Measures of safety included frequencies of adverse experiences and abnormal results on laboratory tests.\n A total of 128 subjects (88% men, 51% white) were enrolled, median age 45 years. Most subjects (62%) had mild to moderate AIDS dementia complex. The 24-week NPZ-6 median (interquartile range) changes were 0.22 (-0.28, 0.55) for the selegiline 3 mg/24 hours arm, 0.21 (-0.18, 0.62) for the selegiline 6 mg/24 hours arm, and 0.28 (-0.16, 0.64) for the placebo arm (a positive score indicates improvement from baseline) (p = 0.914). Severe laboratory abnormalities were few and occurred in similar proportion among the three treatment arms.\n Selegiline was safe and well tolerated by HIV-infected individuals with cognitive impairment and mild to moderate immune suppression; however, no cognitive or functional improvement was observed in this phase II study.", "To assess the safety and efficacy of memantine, an uncompetitive antagonist of the N-methyl-D-aspartate receptor as treatment of HIV-associated cognitive impairment.\n This was a Phase II randomized, double-blind, placebo-controlled, multicenter trial within the Adult AIDS Clinical Trials Group. One-hundred and forty HIV-infected adults with mild to severe AIDS dementia complex receiving stable antiretroviral therapy were enrolled. Memantine was initiated at 10 mg daily escalated to 40 mg daily, or up to the maximum tolerated dose and continued for 16 weeks (primary evaluation visit) followed by a 4-week washout period and re-evaluation at week 20. Changes in cognitive performance were measured as percent change from baseline to week 16 in the average of eight neuropsychological test scores (NPZ-8). Brain metabolism was measured by magnetic resonance spectroscopy in a subgroup of subjects.\n Sixty-one percent of subjects in the memantine group and 85% in the placebo group reached the 40 mg dose while the reported adverse experiences between the two groups were similar. There were no significant improvements in neuropsychological performance over 16 weeks; however, memantine was associated with a significant increase at week 16 in the N-acetyl aspartate to creatine ratio, in the frontal white matter (P = 0.040) and parietal cortex (P = 0.023).\n Memantine was safe and tolerated by HIV-infected subjects with cognitive impairment. Although we observed no significant differences in cognitive performance, the magnetic resonance spectroscopy data suggest that memantine may ameliorate neuronal metabolism, an important step to stabilizing or preventing neuronal injury. These results underscore the need for longer studies to assess the full potential of neuroprotective agents.", "Few effective treatments are available for AIDS dementia complex (ADC) and HIV-associated neuropathy. However, recent in vitro studies indicate that nimodipine, a voltage-dependent calcium channel antagonist, can prevent HIV-related neuronal injury and may provide a novel form of treatment for these disorders.\n To determine the safety and possible efficacy of this agent, 41 patients with mild to severe ADC, including 19 patients with neuropathy, were entered into the AIDS Clinical Trial Group multicenter, phase-I and phase-II study. Nimodipine at 60 mg p.o., five times daily; 30 mg p.o., three times daily; or placebo was administered for 16 weeks as adjuvant treatment to antiretroviral therapy.\n Neuropsychological performance at baseline, measured by the composite neuropsychological Z score (NPZ-8), correlated significantly with the ADC stage and with CSF levels of neopterin, a marker of immune activation. No significant differences in toxicity were observed among the three arms. Intent-to-treat analysis showed no significant change in the NPZ-8, although improvement was suggested in the high-dose arm. In addition, a trend toward stabilization in peripheral neuropathy was observed in both nimodipine arms compared with placebo.\n Nimodipine and other similar nonantiretroviral agents may provide a safe and promising avenue of treatment for neurologic disorders associated with HIV infection. The results of this study indicate that further clinical trials are warranted.", "To assess the safety and tolerability of lexipafant in HIV-associated cognitive impairment.\n Cognitive impairment is the most common neurologic complication of advanced HIV-1 infection. There is evidence that a variety of inflammatory mediators, including platelet-activating factor (PAF), may contribute to neuronal injury. We hypothesized that lexipafant, a PAF antagonist, might improve cognitive dysfunction in HIV-infected people.\n We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the safety and tolerability of lexipafant 500 mg/day. The primary outcome measure for tolerability was the ability to complete the study on the originally assigned dosage of medication. Thirty patients with cognitive impairment were enrolled.\n Lexipafant was safe and well tolerated. Ninety-three percent in the placebo group and 88% in the lexipafant group completed the study at the originally assigned dosage. Trends toward improvement were seen in neuropsychological performance, especially verbal memory, in the lexipafant treatment group.\n This study shows that lexipafant, the first PAF antagonist used in HIV-associated cognitive impairment, is a safe and well tolerated compound. The observed trends toward improvement in neuropsychological test scores warrant the pursuit of a larger and longer efficacy trial to assess the impact of lexipafant on cognitive performance.", "D-Ala1-peptide T-amide (DAPTA) has shown neuroprotection in vitro against gp120-induced loss of dendritic arborization and is promulgated as a CCR5 antagonist. A multisite, randomized, double-blind clinical trial of DAPTA versus placebo prior to combination antiretroviral therapy conducted with human immunodeficiency virus (HIV)-1 seropositive participants having cognitive impairment showed no overall cognitive effect, though subgroups with greater impairment and CD4 cell counts of 201 to 500 cells/mm3 at baseline showed significant improvement. The objective of this study was to examine whether intranasal administration of DAPTA at a dose of 2 mg three times per day (tid) was associated with a reduction of cerebrospinal fluid (CSF) and peripheral (plasma and serum) viral load among a subgroup of participants completing 6 months of treatment. Baseline and 6-month CSF (n = 92) and peripheral (plasma n = 33; serum n = 24) viral load were measured by the Roche Ultrasensitive assay, version 1.5, with reflexive use of the AMPLICOR assay and preservation of the blind. A DAPTA treatment indicator variable was tested using generalized linear models on change in viral load. Peripheral load (combined plasma and serum) was significantly reduced in the DAPTA-treated group. No group differences in CSF viral load were found. This retrospective study on a limited subgroup of the original trial sample indicated that DAPTA treatment may reduce peripheral viral load without concomitant CSF effects. Future studies should be undertaken to confirm the existence of this result and the CSF-periphery dissociation observed with respect to HIV-1-associated cognitive-motor impairment." ]

[ "8210390" ]

[ "Diffuse panbronchiolitis: follow-up CT examination." ]

[ "The authors reviewed serial computed tomographic (CT) scans obtained in 19 patients with diffuse panbronchiolitis (DPB) to evaluate changes in disease pattern over time.\n Nineteen patients with DPB were entered into the study. After initial CT examination, 12 patients were randomly assigned to receive long-term low-dose (200 mg three times daily) erythromycin therapy; seven patients received no treatment.\n Follow-up CT scans revealed that centrilobular areas of high attenuation observed initially had progressed to dilatation of the proximal airway in some patients in the untreated group. In the treated group, the centrilobular and branched linear areas of high attenuation were decreased in number and size, although the airway dilatation and decreased lung attenuation in the peripheral areas remained unchanged or were slightly increased.\n CT scans are valuable in the study of the disease process and response to therapy in DPB." ]

[ "2943311", "10634370", "2516705", "15181054", "7829618", "2690044", "2936373", "3967781", "12749435" ]

[ "Oral spironolactone: an effective treatment for acne vulgaris in women.", "Comparison of spironolactone, flutamide, and finasteride efficacy in the treatment of hirsutism: a randomized, double blind, placebo-controlled trial.", "Dexamethasone and spironolactone in the treatment of non-tumorous hyperandrogenism.", "Comparison of efficacy of spironolactone with metformin in the management of polycystic ovary syndrome: an open-labeled study.", "A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute women.", "Lack of effect of spironolactone on hair shaft diameter in hirsute females.", "Lack of effect of topical spironolactone on sebum excretion.", "The effects of two doses of spironolactone on serum androgens and anagen hair in hirsute women.", "Use of cyproterone acetate, finasteride, and spironolactone to treat idiopathic hirsutism." ]

[ "The effect of oral spironolactone (200 mg daily) on acne vulgaris has been studied in 21 women in a randomized, placebo-controlled, double-blind crossover study using 3 month treatment periods. Compared with placebo, spironolactone produced significant improvement as assessed by subjective benefit (P less than 0. 001), number of inflamed lesions (P less than 0 . 001) and by an independently evaluated photographic method (P less than 0 .02). There was a fall in sex hormone binding globulin but no significant changes in plasma testosterone and derived free testosterone. Initial plasma androgen levels were no higher in responders than in non-responders, nor did oral contraceptive use appear to affect clinical response. Spironolactone is a useful alternative therapy for women with acne vulgaris.", "To compare objectively the efficacies of spironolactone (100 mg/day), flutamide (250 mg/day), and finasteride (5 mg/day) in the treatment of hirsutism, 40 hirsute women were randomly assigned to double blind treatments with 1 of these 3 drugs or placebo for 6 months. Before and at the end of treatment, hirsutism was quantitatively measured in each subject by determination, by computer-assisted light microscopy, of the largest diameter of 5 hairs plucked from the linea alba. These measurements were averaged to produce a mean hair shaft diameter. For each subject, baseline and posttreatment assessments were carried out at the same time by an investigator blinded to both time and type of therapy. In addition, a semi-quantitative clinical evaluation was carried out by a modification of the Ferriman-Gallwey (F-G) scoring method, performed by a single investigator. At baseline the 4 groups of women had similar hair diameters and F-G scores. After 6 months of therapy all groups of subjects given active drugs showed reductions of their hair diameters, without statistically significant differences among groups (mean change +/- SEM, -11.7+/-5.6%, -18.0+/-6.1%, and -12.6+/-6.7%, respectively, in the spironolactone, flutamide, and finasteride groups). F-G scores were also significantly reduced in women receiving antiandrogen drugs, again without differences among groups (mean change, -41.0+/-5.5%, -38.9+/-7.2%, and -31.6+/-3.7%, respectively). No significant changes from baseline values were recorded by either hair diameter (-1.4+/-5.2%) or F-G score (+5.4+/-3.7%) assessment in the placebo group. In conclusion, spironolactone, flutamide, and finasteride are all effective in the treatment of hirsutism. After a 6-month course of therapy, the clinical efficacies of these drugs, at least at the doses used, are similar.", "To test the hypothesis that a combination therapy with dexamethasone and spironolactone in hirsute women with menstrual disorders due to non-tumorous hyperandrogenism might yield better results than monotherapy with spironolactone, we evaluated 25 women randomly assigned to dexamethasone-spironolactone (n = 15) and spironolactone (n = 10) groups. The Ferriman-Gallwey score and hormonal levels (LH, FSH, PRL, serum testosterone, androstenedione, dehydroepiandrosterone sulfate, estradiol, estrone and salivary testosterone) were determined before and after 6 months of therapy. There were comparable results, with a significant drop in the Ferriman-Gallwey score, in serum androstenedione and estrone concentrations and in salivary testosterone levels in both groups. The only difference between the two groups after therapy was a significant fall in serum dehydroepiandrosterone levels in patients treated with the combination therapy. The results indicate that the combination therapy with spironolactone and dexamethasone presents no real advantage over therapy with spironolactone alone, for the initial treatment of non-tumorous hyperandrogenism.", "We compared the efficacy of spironolactone (50 mg/d) with metformin (1000 mg/d) after random allocation in 82 adolescent and young women with polycystic ovary syndrome (PCOS) on body mass index (BMI), waist-to-hip ratio, blood pressure, menstrual cyclicity, hirsutism, hormonal levels, glycemia, and insulin sensitivity at baseline and at the 3rd and 6th months of treatment. Sixty-nine women who completed the follow-up had a mean age of 22.6 +/- 5.0 yr and mean BMI of 26.8 +/- 4.0 kg/m2. The number of menstrual cycles in the spironolactone and metformin groups increased from 6.6 +/- 2.1 and 5.7 +/- 2.3 at baseline to 9.0 +/- 1.9 and 7.4 +/- 2.6 at 3rd month and to 10.2 +/- 1.9 and 9.1 +/- 2.0/ year at the 6th month (P = 0.0037), respectively. The hirsutism score decreased from 12.9 +/- 3.2 and 12.5 +/- 4.9 at baseline to 10.1 +/- 3.1 and 11.4 +/- 4.1 at the 3rd month and to 8.7 +/- 1.9 and 10.0 +/- 3.3 at the 6th month, respectively. Both groups showed improvement in glucose tolerance and insulin sensitivity, although the metformin effect was significant in the latter. Serum LH/FSH and testosterone decreased in both groups. BMI, waist-to-hip ratio, and blood pressure did not change with either drug. We conclude that both drugs are effective in the management of PCOS. Spironolactone appears better than metformin in the treatment of hirsutism, menstrual cycle frequency, and hormonal derangements and is associated with fewer adverse events.", "Enhanced 5 alpha-reductase activity has been found in the skin of the majority of women with hirsutism. Finasteride is a specific competitive inhibitor of 5 alpha-reductase, preferentially inhibiting the type 2 isoenzyme. Therefore, we randomly assigned 14 hirsute women in a 2:1 ratio to 1 of 2 treatment arms: 1) finasteride (F) treatment (n = 9; 5 mg, orally, daily), or 2) spironolactone (S) treatment (n = 5; 100 mg, orally, daily). Each group was treated for 6 months. Patients were evaluated at baseline and after 3 and 6 months of treatment. The 2 groups were similar in age, weight, hip/waist ratio, baseline Ferriman-Gallwey score (F, 19 +/- 2; S, 19 +/- 2), and baseline androgen levels. Finasteride treatment resulted in a significant increase in testosterone (T; P < 0.01) and the T/dihydrotestosterone ratio (P < 0.01). Finasteride caused a significant decrease in 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (3 alpha-diolG; P < 0.05), the 3 alpha-diolG/T ratio (P < 0.01), and the 3 alpha-diolG/androstenedione ratio (P < 0.05). All changes were consistent with 5 alpha-reductase inhibition. In contrast, spironolactone treatment did not result in significant changes in serum hormone levels. Both treatments produced a significant decrease in anagen hair diameters [F, -14.0 +/- 6.7% (P < 0.05); S, -13.4 +/- 3.8% (P < 0.05)] and Ferriman-Gallwey scores [F, -2.1 +/- 0.4 (P < 0.05); S, -2.5 +/- 0.7 (P < 0.05)]. In conclusion, despite significantly different effects on androgen levels, finasteride and spironolactone treatment resulted in a similar clinical effect on hirsutism. Both caused significant, but limited, improvement in hirsutism. Although promising, further studies with finasteride are needed to verify its effectiveness as a treatment for hirsutism. Such studies will also provide a better understanding of the relative contribution of 5 alpha-reductase isoenzymes to hirsutism.", "Because of its anti-androgenic activity spironolactone 50-200 mg daily is advocated widely for the management of female hirsutism but this practice lacks adequately controlled experimental support. In a double-blind placebo controlled study of the efficacy of spironolactone 100 mg daily in idiopathic hirsutism we were unable to demonstrate objective benefit from spironolactone treatment. The mean effect of spironolactone given over a 9 month period was to increase hair shaft diameter by +15% with 95% CI (-0.4% to +29%). In addition there were no changes in circulating serum androgen concentrations.", "nan", "Spironolactone (S) has been used successfully for the treatment of hirsutism. We evaluated whether the effects of S on serum androgens and hair growth are dose-related and whether S affects secreted androgens to the same degree as peripherally derived androgens. Two groups of 15 hirsute patients, similarly matched, received either 100 or 200 mg S daily for 3 months. Serum total testosterone (T) decreased significantly (P less than 0.05) and to a similar degree with both dosages, whereas unbound T was unaltered. Dehydroepiandrosterone sulfate was unaltered, whereas androstenedione decreased with 200 mg S (P less than 0.05). Peripherally derived serum dihydrotestosterone decreased to a similar degree with 100 and 200 mg S (P less than 0.05), whereas 5 alpha-androstane-3 alpha-17 beta-diol (3 alpha-diol) increased (P less than 0.05) similarly with both dosages. Serum 3 alpha-diol glucuronide (3 alpha-diol-G) increased with both dosages, but not significantly. Anagen hair shaft diameters decreased significantly in both groups by 19% +/- 8% and 30% +/- 4% (P less than 0.05). No correlation was found between hair growth and serum androgens. Because serum unbound T was largely unaltered by S, it is suggested that the antiandrogenic effects of S are primarily related to its peripheral effect. However, there is no good clinical marker for this effect as levels of 3 alpha-diol and 3 alpha-diol-G increase.", "To compare the effectiveness of cyproterone acetate, finasteride, and spironolactone in the treatment of idiopathic hirsutism.\n Prospective randomized clinical study.\n University hospital.\n Forty-one women (median age, 21 years [range, 18-34 years]) with idiopathic hirsutism who had requested to use an oral contraceptive.\n Patients were randomly assigned to receive cyproterone acetate (12.5 mg/d for the first 10 days of the cycle), finasteride (5 mg/d), or spironolactone (100 mg/d) for 12 months. Follow-up was done at the end of therapy.\n Ferriman-Gallwey score before treatment, at 6 and 12 months of treatment, and 1 year after the end of treatment, and androgenic profile before and after treatment.\n At the end of therapy, the Ferriman-Gallwey score decreased by 38.9%, 38.6%, and 38.5% in patients who used cyproterone acetate, finasteride, and spironolactone, respectively. One year after therapy, the Ferriman-Gallwey score of patients who used spironolactone was significantly lower (6.74 +/- 1.41) than that of patients who used either cyproterone acetate (7.92 +/- 1.08), or finasteride (9.08 +/- 0.99). The androgenic profile did not change significantly during treatment.\n In patients with idiopathic hirsutism, the short-term results of treatment with cyproterone acetate, finasteride, and spironolactone are similar, but spironolactone is effective for a longer time." ]

[ "9647873", "17243135" ]

[ "Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography.", "Intra-individual variation in blood flow velocities in cerebral arteries of children with sickle cell disease." ]

[ "Blood transfusions prevent recurrent stroke in children with sickle cell anemia, but the value of transfusions in preventing a first stroke is unknown. We used transcranial Doppler ultrasonography to identify children with sickle cell anemia who were at high risk for stroke and then randomly assigned them to receive standard care or transfusions to prevent a first stroke.\n To enter the study, children with sickle cell anemia and no history of stroke had to have undergone two transcranial Doppler studies that showed that the time-averaged mean blood-flow velocity in the internal carotid or middle cerebral artery was 200 cm per second or higher. The patients were randomly assigned to receive standard care or transfusions to reduce the hemoglobin S concentration to less than 30 percent of the total hemoglobin concentration. The incidence of stroke (cerebral infarction or intracranial hemorrhage) was compared between the two groups.\n A total of 130 children (mean [+/-SD] age, 8.3+/-3.3 years) were enrolled; 63 were randomly assigned to receive transfusions and 67 to receive standard care. At base line, the transfusion group had a slightly lower mean hemoglobin concentration (7.2 vs. 7.6 g per deciliter, P=0.001) and hematocrit (20.4 vs. 21.7 percent, P=0.002). Ten patients dropped out of the transfusion group, and two patients crossed over from the standard-care group to the transfusion group. There were 10 cerebral infarctions and 1 intracerebral hematoma in the standard-care group, as compared with 1 infarction in the transfusion group -- a 92 percent difference in the risk of stroke (P<0.001). This result led to the early termination of the trial.\n Transfusion greatly reduces the risk of a first stroke in children with sickle cell anemia who have abnormal results on transcranial Doppler ultrasonography.", "Children with sickle cell disease (SCD) are at elevated risk of stroke. Risk increases with blood flow velocity in selected cerebral arteries, as measured by transcranial Doppler (TCD) ultrasound, and use of TCD to screen these patients is widely recommended. Interpretation of TCD results should be based on knowledge of intra-individual variation in blood flow velocity, information not currently available for sickle cell patients.\n Between 1995 and 2002, 4,141 subjects, 2-16 years old, with homozygous SCD or Sbeta0-thalasemmia and no history of stroke were screened with TCD, including 2,018 subjects screened in one clinical trial (STOP), 1,816 screened in another (STOP 2), and 307 screened in an interim ancillary prospective study. The 812 subjects with >or=2 examinations<6 months apart were selected for analysis, including 242 (29.8%) subjects with normal average velocities (i.e., <170 cm/sec), 350 (43.1%) subjects with conditional velocities (i.e., 170-199 cm/sec), and 220 (27.1%) subjects with abnormal velocities (i.e., >or=200 cm/sec). The intra-subject standard deviation of TCD velocity was estimated from the difference between velocities at the first two interpretable examinations on each subject.\n An intra-subject standard deviation of 14.9 cm/sec was obtained. Seven (0.9%) subjects had unusually large and unexplained differences between velocities at the two examinations (range of absolute differences: 69-112 cm/sec).\n While stroke risk is well demonstrated to increase with increasingly abnormal TCD velocity, given the relatively large intra-subject variability, one TCD examination is generally not sufficient to characterize stroke risk in this patient population.\n Copyright (c) 2007 Wiley-Liss, Inc." ]

[ "10661672", "11906805", "8241923", "12022799", "8678182" ]

[ "Reinforcement-based intensive outpatient treatment for inner city opiate abusers: a short-term evaluation.", "Evaluation of an alternative program for MMTP drop-outs: impact on treatment re-entry.", "Does post-withdrawal cue exposure improve outcome in opiate addiction? A controlled trial.", "Voucher reinforcement for heroin and cocaine abstinence in an outpatient drug-free program.", "Efficacy of enhanced outreach counseling to reenroll high-risk drug users 1 year after discharge from treatment." ]

[ "We evaluated 3-month outcomes for reinforcement-based intensive outpatient treatment (RBT), a new relapse prevention behavior therapy for inner city opiate abusers. The therapy provides abstinence-contingent partial support of housing, food and recreational activities, abstinence-contingent access to social skills and job finding group therapy and non-contingent individual counseling, all in the context of a day treatment program. Heroin abusers (n = 52), contacted at a 3-day detoxification unit, were randomly assigned to RBT (n = 28) or referred to community treatment resources (n = 24) after a staff escort from the detoxification unit. For RBT patients, treatment began on the day of discharge; 61% received partial rent support in a recovery house based on the need for drug-free housing; the remainder were eligible for partial support of utility payments where they lived. Abstinence-based contingencies were in effect for 1 month with three times per week counseling available for an additional 2 months. One month after detoxification, 61% of RBT versus 17% of referral patients were enrolled in outpatient treatment (P < 0.01); RBT patients were significantly less likely than controls to have returned to any drug use; and 50% of RBT versus 21% of controls reported 30 days of abstinence from heroin and cocaine with confirmatory negative urine (P < 0.05). RBT patients had significantly lower scores on the Beck Depression Inventory at 1 month (M = 9.0 versus 17.6 for controls; P < 0.05) and showed evidence of less alcohol use and higher rates of employment. These results establish the short-term efficacy for RBT and support continued development and evaluation of this new outpatient behavioral treatment.", "Retention in a Methadone Maintenance Treatment Program (MMTP) is predictive of abstaining from heroin and has other benefits. Many individuals leave treatment before they experience these positive outcomes.\n This research project targeted MMTP drop-outs with an intervention designed to assist them in returning to drug treatment.\n Subjects who had left MMTP within the prior 12 months were randomly assigned to intervention or comparison groups. The 3-month long intervention consisted of street outreach, cognitive behavioral groups, and individual counseling. Data were analyzed for 175 subjects who were out of treatment at baseline and who returned for a 6-month follow-up interview (Intervention group, N=111; Comparison group, N=64).\n A total of 87% of subjects assigned to the intervention condition participated in at least one component. Intervention subjects who attended two or more cognitive behavioral group sessions were more likely than those who attended 0-1 sessions or those in the comparison group to have returned to treatment during the 6 month follow up time period (72 vs. 53 vs. 50%, respectively, P<0.05, chi square test).\n MMTP drop-outs need not be lost to the drug treatment system if special efforts are made to engage them in interventions developed to encourage treatment re-entry.", "A controlled trial studied whether cue exposure prevented relapse in opiate addiction. Subjects were randomly allocated to one of two inpatient treatment settings: a drug dependence unit with a special 10 week program and 4 weeks in a behavioural/general treatment unit without such a program. In each setting, following drug-withdrawal, subjects had either cue exposure for at least six sessions over 3 weeks, or a control condition. Subjects were followed up twice, at about 6 weeks and 6 months post-treatment. 186 subjects were randomly allocated; 69 were assessed post-detoxification, and of these 43 completed cue exposure or control treatments. Cue exposure and control subjects did not differ in cue reactivity. This was evaluated post-treatment for cue exposure subjects and at a comparable time point for controls. All groups showed a significant decrement in cue-elicited craving, withdrawal responses and negative mood. Cue exposure and control subjects did not differ at either of the two follow up interviews.", "This study examined an abstinence-contingent voucher incentive program in opiate-dependent clients enrolled in outpatient drug-free (nonmethadone) treatment. Study participants were referred from local detoxification programs and randomly assigned to voucher (n = 29) or no-voucher (n = 23) conditions. Both groups received intensive cognitive-behavioral counseling; those in the voucher condition could earn up to $1,087.50 over 3 months for submitting urines negative for both opiates and cocaine. Voucher versus no-voucher groups did not differ significantly on mean days retained in treatment (35.9 vs. 39.3 days), mean number of opiate- and cocaine-negative urines submitted (8.3 vs. 6.2), longest duration of continuous abstinence (16.8 vs. 12.1 days), or percentage of participants abstinent for 4 weeks (20.7% voucher vs. 9% no voucher). Possible reasons for negative findings are discussed. Findings suggest that voucher programs must be better tailored to the clinical population and behavioral targets being addressed.", "Because discharged methadone maintenance patients represent a population at particularly high public health risk, the authors studied such patients 1 year after their discharge from a methadone program.\n The locations of 94 of 110 discharged patients were successfully determined 1 year after discharge. Nine (10%) of these patients had died, 37 (39%) were already reenrolled in treatment, and 7 (7%) did not require treatment. The 41 remaining subjects were randomly assigned to either the enhanced outreach counseling condition (N = 27) or a standard referral condition (N = 14).\n Within 2 weeks following this intervention, 17 (63%) of the 27 patients in the enhanced outreach counseling program and one (7%) of the 14 patients not in the program had reenrolled in treatment.\n These data suggest that enhanced outreach counseling may be an effective outreach strategy as well as a risk-reduction for discharged methadone maintenance patients." ]

[ "10213329", "3895410", "9666761", "11516807", "11248608", "6337667", "14713803", "10828671", "14678372", "10543335", "8937366", "11176403", "9144906", "3516295", "9467475", "10824450", "7006730", "7049301", "15302476", "15041104", "2675580", "12028165", "12028164", "9863850", "12962951", "15540755", "15126811", "1771701", "11454106", "12893326", "10510109", "15455256", "2249115", "14764127", "2198921", "10210394", "7484484", "6370504", "2005707" ]

[ "Efficacy and safety of propiverine in SCI-patients suffering from detrusor hyperreflexia--a double-blind, placebo-controlled clinical trial.", "Emepronium carrageenate: clinical effects and urinary excretion in treatment of female urge incontinence.", "Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder.", "Tolterodine reduces the number of urge incontinence episodes in patients with an overactive bladder.", "Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder.", "Placebo--the drug of choice in female motor urge incontinence?", "Efficacy of antimuscarinic therapy for overactive bladder with varying degrees of incontinence severity.", "Efficacy and cardiac safety of propiverine in elderly patients - a double-blind, placebo-controlled clinical study.", "Solifenacin appears effective and well tolerated in patients with symptomatic idiopathic detrusor overactivity in a placebo- and tolterodine-controlled phase 2 dose-finding study.", "Clinical efficacy and safety of tolterodine compared to oxybutynin and placebo in patients with overactive bladder.", "Urinary urge incontinence: randomised crossover trials of penthienate versus placebo and propantheline.", "Intravesical electromotive administration of oxybutynin in patients with detrusor hyperreflexia unresponsive to standard anticholinergic regimens.", "Efficacy and safety of two doses of tolterodine versus placebo in patients with detrusor overactivity and symptoms of frequency, urge incontinence, and urgency: urodynamic evaluation. The International Study Group.", "Dose titration in clinical trials. An example using emepronium carrageenate in detrusor instability.", "Efficacy and safety of tolterodine in patients with detrusor instability: a dose-ranging study.", "[Assessment of effectiveness of and tolerance to oxybutynin in the treatment of unstable bladder in women].", "The urodynamic and subjective results of treatment of detrusor instability with oxybutynin chloride.", "Urinary incontinence in old age. A controlled clinical trial of emepronium bromide.", "Treatment of urge-predominant mixed urinary incontinence with tolterodine extended release: a randomized, placebo-controlled trial.", "Darifenacin, an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder.", "Oxybutynin chloride for geriatric urinary dysfunction: a double-blind placebo-controlled study.", "Urodynamic changes associated with behavioral and drug treatment of urge incontinence in older women.", "Efficacy, safety, and tolerability of extended-release once-daily tolterodine treatment for overactive bladder in older versus younger patients.", "Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial.", "Reduced perception of urgency in treatment of overactive bladder with extended-release tolterodine.", "Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder.", "Trospium chloride improves overactive bladder symptoms: a multicenter phase III trial.", "Effect of trospium chloride on urodynamic parameters in patients with detrusor hyperreflexia due to spinal cord injuries. A multicentre placebo-controlled double-blind trial.", "Tolterodine: a safe and effective treatment for older patients with overactive bladder.", "Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence.", "A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence.", "Health-related quality of life of Japanese patients with overactive bladder treated with extended-release tolterodine or immediate-release oxybutynin: a randomized, placebo-controlled trial.", "Oxybutynin hydrochloride (3 mg) in the treatment of women with idiopathic detrusor instability.", "Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder.", "The treatment of detrusor instability in post-menopausal women with oxybutynin chloride: a double blind placebo controlled study.", "Clinical efficacy and safety of tolterodine compared to placebo in detrusor overactivity.", "Oxybutynin with bladder retraining for detrusor instability in elderly people: a randomized controlled trial.", "Oxybutynin chloride in the treatment of female idiopathic bladder instability. Results from double blind treatment.", "Randomized, double-blind, multicenter trial on treatment of frequency, urgency and incontinence related to detrusor hyperactivity: oxybutynin versus propantheline versus placebo." ]

[ "The aim of this double-blind, randomised, prospective, multicentre trial was to evaluate the efficacy of propiverine in patients suffering from detrusor hyperreflexia caused by spinal cord injury in comparison to placebo.\n The treatment period of 14 days comprised visits at baseline (V1) and after 14 days treatment (V2). Fifteen mg propiverine t.i.d. or placebo t.i.d. were administered as medication. The following efficacy parameters were adopted: the urodynamic parameters maximal cystometric bladder capacity, bladder volume on onset of the first as well as duration and amplitude of the maximum detrusor contraction, bladder compliance and residual urine, and subjective assessment of efficacy by physicians. For the evaluation of the safety of propiverine the incidence rate of adverse events by directly questioning as well as laboratory parameters were investigated. For biometrical evaluation t-test for independent groups was applied.\n One hundred and thirteen patients were investigated. The maximal cystometric bladder capacity increased significantly in the propiverine group, on average by 104 ml (V1: 262+/-132 ml. V2: 366+/-143 ml, P<0.001). The changes in bladder capacity during the first contraction and the maximum detrusor contraction in the verum group were both statistically significant. The bladder compliance documented a more pronounced increase under propiverine in comparison to placebo. Residual urine increased by 37+/-71 ml in the propiverine group, significantly more than in the placebo group (P=0.01). Sixty-three per cent of the patients expressed subjectively an improvement under propiverine in comparison with 23% of the placebo group. Expected anticholinergic adverse events occurred: dryness of the mouth (37% in the verum and 8% in the placebo group), accommodation disorders (28% and 2% respectively). Nausea, constipation, headache, dizziness, tiredness and palpitations were reported in almost comparable incidence rates between 3 and 13% in both treatment groups. Eight drop-outs were registered in the propiverine group (five due to adverse events) and three in the placebo group (one due to adverse events). The laboratory parameters revealed no changes.\n Propiverine proved its efficacy in detrusor hyperreflexia with regard to the urodynamic parameters of the maximal cystometric bladder capacity and detrusor contractility. Anticholinergic adverse events such as dryness of the mouth and accommodation disorders were considered being tolerable. The increase in residual urine reflects the therapeutically desired effect of detrusor relaxation because the majority of patients normally practise intermittent catheterisation for bladder emptying.", "Eighteen women (median age 54 years, 36-79) with urinary motor urge (n = 13) or sensory urge (n = 5) incontinence were treated for three 2-week periods with emepronium carrageenate (EC) (Cetiprin Novum) in daily doses of 500 and 1000 mg and placebo. Subjectively the women experienced an increased ability to control micturition, i.e. less urge, during EC treatment. Only mild and mainly anticholinergic side effects were recorded, most frequently dryness of the mouth. As regards side effects, the evaluation of objective effects were complicated by a tendency towards carry-over effect to placebo. Placebo in the first treatment periods were analysed solely; no effects of placebo could be demonstrated. Compared with the reference period, decreases in the total number of micturitions (approx. 20%) and in the number of urge incontinence episodes (approx. 75%) were seen. As compared with placebo, a significant increase (approx. 25%) in the average micturition volume could be demonstrated. The percentage urinary excretion of emepronium decreased with increasing oral intake and with advancing age. Probably, an initial daily dosage of 500 mg EC will do well in younger women (less than 50 years), whereas elder patients may need 1000 mg. Further dosage recommendations are given.", "To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder.\n A randomized, double-blind, placebo-controlled, parallel group, multinational phase-III study was conducted in urology and gynaecology clinics in the UK, Republic of Ireland and Sweden. The study enrolled 293 patients with urodynamically confirmed bladder overactivity, increased frequency of micturition (> or = micturitions/24 h) and symptoms of urgency and/or urge incontinence (> or = 1 episode/24 h). Patients received either tolterodine (2 mg twice daily) or oxybutynin (5 mg three times daily) or placebo. Doses could be reduced, to prevent withdrawal, to 1 mg or 2.5 mg, respectively. The main outcome measures were the mean change from baseline in frequency of micturition/24 h, the number of incontinent episodes/24 h and volume voided per micturition.\n After 12 weeks' treatment, the mean frequency of micturition decreased by 21% and 19.5% in those receiving tolterodine (n = 118) and oxybutynin (n = 118), respectively, and by 10.5% in those on placebo (n = 57). Among those with urge incontinence at baseline (75% of patients), the mean number of incontinent episodes decreased by 47%, 71% and 19%, respectively, in those receiving tolterodine, oxybutynin and placebo. The effect of tolterodine and oxybutynin on these two micturition variables was statistically equivalent. There was also a comparable increase in mean volume voided per micturition in the tolterodine (27%) and oxybutynin groups (31%), compared with 7% in the placebo group. Dry mouth was the most common adverse event and was reported with greater frequency and intensity among patients receiving oxybutynin than among those receiving either tolterodine or placebo. In the oxybutynin group, more patients also withdrew because of adverse events and a greater proportion required dose reduction as a result of adverse events. Despite dose reduction, the frequency of adverse events and the intensity of dry mouth remained higher among those receiving oxybutynin (2.5 mg three times daily) than in patients who remained on tolterodine 2 mg twice daily.\n Tolterodine 2 mg twice daily is effective and well tolerated in the treatment of bladder overactivity. Tolterodine was better tolerated than oxybutynin, particularly with respect to the frequency and intensity of dry mouth, but had comparable clinical efficacy. The superior tolerability of tolterodine therefore allows more patients to remain on effective therapy than the current most commonly prescribed agent for the treatment of the overactive bladder.", "To evaluate the efficacy, safety and tolerability of tolterodine compared to placebo in patients with an overactive bladder.\n A double-blind, multi-centre phase III study in France and Belgium 251 patients with overactive bladder symptoms, and urodynamically verified detrusor overactivity, were randomised to receive 4-week treatment with either placebo or tolterodine 1 or 2mg twice daily (bd). Efficacy was evaluated from patient micturition diaries. Safety and tolerability endpoints were also evaluated.\n After 4-week treatment, the number of incontinence episodes/24h decreased significantly relative to placebo in the tolterodine 1 and 2 mgbd groups (P=0.045 and P=0.0089, respectively). Both dosages of tolterodine increased volume voided per micturition compared with placebo (P=0.055 and P=0.056, respectively), although significant decreases in micturition frequency were not apparent. Tolterodine was safe and well tolerated, few patients were withdrawn due to adverse events. Dry mouth, mainly of mild-to-moderate intensity, was the most common adverse event. No clinically relevant changes in blood pressure or laboratory safety variables were reported.\n Tolterodine is effective, safe and well tolerated for the treatment of symptoms of an overactive bladder, particularly urge incontinence.", "To evaluate the efficacy and tolerability of a new extended-release (ER), once-daily, capsule formulation of tolterodine, relative to placebo and the existing immediate-release (IR), twice-daily, tablet formulation, for treatment of the overactive bladder.\n This was a double-blind, multicenter, randomized, placebo-controlled trial. One thousand five hundred twenty-nine patients (81% women) with urinary frequency (eight or more micturitions every 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral therapy with tolterodine ER 4 mg once daily (n = 507), tolterodine IR 2 mg twice daily (n = 514), or placebo (n = 508) for 12 weeks. Efficacy was assessed at the end of the treatment period on the basis of the micturition diary variables. Tolerability and safety were assessed by evaluating the adverse events, electrocardiogram parameters, laboratory values, and treatment withdrawals.\n Tolterodine ER 4 mg once daily (P = 0.0001) and tolterodine IR 2 mg twice daily (P = 0.0005) both significantly reduced the mean number of urge incontinence episodes per week compared with placebo. The median reduction in these episodes as a percentage of the baseline values was 71% for tolterodine ER, 60% for tolterodine IR, and 33% for placebo. The ER formulation was 18% more effective than the IR formulation (P <0.05). Treatment with both formulations of tolterodine was also associated with statistically significant improvements in all other micturition diary variables compared with placebo. For both formulations, the mean decreases in micturition frequency (P <0.0079) and pad usage (P <0.0145) were significant, and the mean volume voided per micturition increased (P = 0.0001). The rate of dry mouth (of any severity) was 23% for tolterodine ER, 30% for tolterodine IR, and 8% for placebo. The overall dry mouth rate for patients taking tolterodine ER was 23% lower than for tolterodine IR (P <0.02), and the rate of severe dry mouth in the ER group was only 1.8%. The rates of withdrawal were comparable for the two active groups and the placebo group. No safety concerns were noted.\n Tolterodine ER 4 mg once daily is effective and well tolerated in the treatment of overactive bladder with no safety concerns. Tolterodine ER demonstrated an improved efficacy for reducing urge incontinence episodes and a lower frequency of dry mouth compared with the existing IR twice-daily formulation.", "In a randomised double-blind cross-over trial of 19 females with motor urge incontinence but without bladder suspension defect, the effects of 14 days' treatment with emepronium bromide 200 mg qid, flavoxate chloride 200 mg qid or placebo qid were compared by means of micturition charts, the patients' drug preferences and evaluation of side effects. Placebo was the only drug giving rise to a statistically significant decrease in the frequency of voidings, incontinence and nocturia. Forty-seven per cent of the patients preferred placebo and side effects were less frequent during treatment with this medication. No differences could be demonstrated between the effects of emepronium bromide and flavoxate chloride. Perhaps detrusor instability is not always the main reason for the voiding dysfunction in these patients, in whom the effect of placebo was equal or superior to the effect of \"active drugs\" and superior to no treatment at all.", "We analyze the efficacy of tolterodine extended release (ER) for overactive bladder in patients with severe incontinence.\n Patients with urinary frequency (8 micturitions or greater per 24 hours), urge incontinence (5 episodes or greater a week) and symptoms of overactive bladder for 6 months or greater were randomized to treatment with 4 mg tolterodine ER once daily or placebo for 12 weeks. Severe incontinence was defined as 21 episodes or greater per week at baseline. Changes in the number of incontinence episodes per week and micturition frequency after 12 weeks were compared between treatments.\n A total of 986 patients were eligible for this post-hoc analysis. After 12 weeks tolterodine ER produced a significant absolute median reduction in incontinence episodes per week compared to placebo (9.0 vs 5.0, p <0.0001). For patients with severe incontinence at baseline median absolute and percentage reductions in incontinence episodes per week were significantly greater with tolterodine ER than placebo (21.0 vs 9.5, p <0.0001; 67.6% vs 29.8%, p = 0.022). Micturition frequency decreased (p <0.02) and volume voided per micturition (p <0.0001) increased significantly more with tolterodine ER compared with placebo in these patients. For patients with nonsevere incontinence at baseline median reductions in incontinence episodes per week were also significantly greater with tolterodine ER than placebo (6.0 vs 4.0, p <0.0001; 71.4% vs 38.5%, p = 0.026).\n Patients with more severe incontinence at baseline achieved greater absolute reductions in incontinence with tolterodine compared to those with less severe symptoms. The degree of improvement, as measured by percent change, was comparable across the entire range of baseline incontinence severity strata. Benefits of antimuscarinic therapy may be greater in these patients than previously reported.", "The study investigated the efficacy and cardiac safety of propiverine in the elderly, because the induction of life-threatening ventricular arrhythmia has been reported for some drugs prescribed in the therapy of urinary incontinence. Ninety-eight patients (21 male, 77 female; 67.7+/-6.3 years of age) suffering from urgency, urge incontinence or mixed urge-stress incontinence were included in the double-blind, multicentre, placebo-controlled, randomized study. After a 2-week placebo run-in period, the patients received propiverine (15 mg t.i.d.) or placebo (t.i.d.) for 4 weeks. Before (V1, V2) and during the treatment period (V3, V4), standard ECGs and 24-hour long-term ECGs were recorded. Propiverine caused a significant reduction of the micturition frequency (V2: 8.7+/-4.2, V4: 6.5+/-3.2 ml; p< or =0.01), reflected in a significant increase in the average micturition volume (V2: 163.5+/-65.9, V4: 216.3+/-101.5 ml; p< or =0.01) and a significant decrease in episodes of incontinence (-54%; p = 0.048). These findings were confirmed by the overall assessment at V4, in which approximately 90% of patients under propiverine either had no urge incontinence or urge symptoms, or showed improvement. Resting and ambulatory electrocardiograms indicated no significant changes. Neither the frequency-corrected Q-T interval nor other cardiac parameters were relevantly altered. The frequency of cardiac events (Lown classes IVa/b) was random, revealing no difference between placebo and propiverine. The incidence of adverse events was very low (2% dryness of the mouth under propiverine) and confirmed by the findings from the quality of life questionnaires. A favourable benefit-risk ratio without the induction of any cardiac arrhythmia in the treatment of elderly patients suffering from urgency, urge incontinence or combined urge-stress incontinence is therefore proven for propiverine.", "To evaluate the dose-response relationship and safety/tolerability of solifenacin succinate (YM905) in the treatment of overactive bladder (OAB), and to compare its efficacy and safety/tolerability with tolterodine 2 mg twice daily.\n This multicentre study included a 2-week single-blind placebo run-in, a 4-week double-blind placebo-controlled active treatment phase, and a 2-week follow-up. Men and women with an OAB and urodynamic evidence of detrusor overactivity were randomized to placebo or solifenacin 2.5, 5, 10 or 20 mg once daily, or tolterodine 2 mg twice daily.\n Of 265 patients enrolled, 225 were randomized and 192 completed the study. Solifenacin 5, 10 and 20 mg produced statistically significant (P < 0.05) improvements in voids/24 h vs placebo, whereas tolterodine did not; the mean change with tolterodine was between those with solifenacin 2.5 and 5 mg. The outcome was similar for the mean change from baseline to endpoint in mean volume voided/void. For incontinence and urgency episodes/24 h the solifenacin dose groups showed numerically superior changes vs placebo; the mean effects with tolterodine were generally smaller than with solifenacin. Most of the efficacy effect of solifenacin was evident at 2 weeks. Quality-of-life outcomes supported the efficacy results. Solifenacin 5 and 10 mg were well tolerated; there were no serious treatment-related adverse events. The incidence of dry mouth was 14% for solifenacin 5 and 10 mg, 2.6% for placebo and 24% for tolterodine.\n In this study, the 5- and 10-mg doses of solifenacin appeared to be the most clinically effective for treating OAB, considering the balance between efficacy, quality of life and tolerability. From the results of this study solifenacin 5 and 10 mg were selected for further evaluation in large-scale phase 3 studies.", "This study compared the clinical efficacy (determined from micturition diaries) and safety of 12 weeks' treatment with either tolterodine 2 mg twice daily, oxybutynin 5 mg three times daily or placebo in patients with an overactive bladder. A total of 277 patients were randomized and treated at 25 centers. Both tolterodine and oxybutynin significantly increased volume voided/micturition compared to placebo. Both treatment groups evoked greater decreases in micturitions per 24 hours and incontinence episodes per 24 hours compared to placebo; however, only tolterodine was significantly better than placebo in reducing micturition frequency. Tolterodine and oxybutynin were equivalent in their effectiveness. Tolterodine was significantly better tolerated than oxybutynin when adverse events (particularly frequency and intensity of dry mouth), dose reduction and patient withdrawals were considered. Oxybutynin is an effective drug whose frequent adverse effects limit its clinical usefulness. Tolterodine has equivalent efficacy to oxybutynin, but with less severe adverse effects. This will allow patients to receive more effective treatment for their condition, with better compliance.", "To compare the efficacy of penthienate with that of propantheline and placebo for treatment of primary idiopathic detrusor instability.\n Two prospective, randomised, crossover trials (double-blind for penthienate versus placebo and non-blinded for penthienate versus propantheline).\n Urology Clinic of Prince Henry Hospital, Sydney, NSW (an outpatient clinic of a tertiary referral hospital), in 1993-1994.\n Neurologically intact patients with urodynamically proven detrusor instability, urgency and urge incontinence, but no stress incontinence (20 participated in the penthienate/placebo trial and 23 in the penthienate/propanthelin trial).\n Cystometrography results before and after treatment; frequency and volumes of urine voided in weeks 1 and 4 of treatment; and patient scores for degree of continence, side effects, efficacy and acceptability of treatment.\n Penthienate (5 mg), propantheline (15 mg) or placebo (all three times a day) for 4 weeks.\n Penthienate produced significantly greater improvements than placebo in frequency (daytime, P = 0.002; and night-time, P = 0.02), incontinence scores (P = 0.002) and amplitude of unstable detrusor contractions, when present (P = 0.01), and significantly increased diurnal and nocturnal bladder capacity, both on cystometrography (P = 0.003) and by voiding-diary records (P < 0.001). It also increased residual urine volume over the baseline level, but not significantly. Side effects, especially dry mouth, were common with penthienate, and one patient developed urinary retention. Penthienate was significantly better than propantheline in improving cystometric capacity (P = 0.03), and reducing the amplitude of unstable detrusor contractions (P = 0.01), and was perceived as more effective by patients for frequency, nocturia and incontinence.\n Penthienate (5 mg three times a day) was objectively and subjectively significantly better than both placebo and propantheline (15 mg three times a day) for treatment of primary idiopathic detrusor instability.", "About 15% to 20% of patients with detrusor hyperreflexia do not benefit from oral oxybutynin regimens, frequently because of unpleasant side effects. Several reports indicate that intravesical oxybutynin is effective in many of these patients but there are some who still fail to respond.\n A select group of 10 adults with detrusor hyperreflexia unresponsive to standard oral and intravesical oxybutynin regimens were treated at weekly intervals with 5 mg. oxybutynin orally, or 5 mg. oxybutynin in 100 ml. intravesically for 60 minutes of passive diffusion and for 30 minutes with 5 mA. electrical current. Each treatment (plus oral placebo and 2 intravesical controls) was associated with an 8-hour, full urodynamic monitoring session, and periodic blood and bladder content sampling.\n There was no significant objective improvement with oral or intravesical passive diffusion oxybutynin. Conversely there was significant improvement in 5 of 6 objective urodynamic measurements with intravesical electromotive oxybutynin. Plasma profiles were a single peak and decay following oral oxybutynin and 2 distinct peaks with intravesical passive diffusion and electromotive oxybutynin. Area under the curve for intravesical passive diffusion were 709 ng. per 8 hours versus oral 1,485 (p <0.05) versus intravesical electromotive 2,781 (p <0.001). Bladder content samples confirmed oxybutynin absorption. Oral oxybutynin caused anticholinergic side effects in 7 of 10 patients. There were no side effects with intravesical passive diffusion or electromotive administrations.\n Accelerated intravesical administration results in greater bioavailability and increased objective benefits without side effects in previously unresponsive patients compared with oral and intravesical passive diffusion oxybutynin administration.", "Tolterodine is a new competitive muscarinic receptor antagonist developed for the treatment of the unstable bladder. A total of 242 patients were enrolled in a multicenter, multinational, randomized, double-blind, placebo-controlled study conducted over a period of 4 weeks in patients with detrusor overactivity and symptoms of frequency, urgency, and urge incontinence. The objective of the study was to compare the efficacy and safety of tolterodine given at 1 or 2 mg b.i.d. versus placebo. At week 4 a statistically significant increase in the volume at first contraction (p = 0.030) and maximal cystometric capacity (p = 0.034) was only in the tolterodine 2 mg b.i.d. group. Tolterodine was safe and generally well tolerated. The incidence of dry mouth, as the most commonly reported adverse event, was only 9% and of mild to moderate intensity.", "Seventy-two women with proven detrusor instability completed a novel clinical trial of the new anticholinergic emepronium carrageenate (Cetiprin novum), which allowed for dose titration. The tolerated dose has been shown to correlate with the severity of symptoms. Statistically significant improvement was achieved in symptomatic and urodynamic parameters without serious side effects.", "To investigate the efficacy and safety of tolterodine, a new antimuscarinic agent, and define the optimum dosage in patients with symptoms of detrusor instability (urgency, increased frequency of micturition and/or urge incontinence).\n A double-blind, placebo-controlled, multicentre study was carried out; after a 1-week run-in period to establish baseline values, 81 patients were randomized to receive placebo or tolterodine 0.5, 1, 2 or 4 mg twice daily for 2 weeks. Micturition (diary) variables, urodynamics and subjective urinary symptoms were assessed after 2 weeks' treatment.\n A per-protocol analysis of efficacy in 64 patients showed dose-related improvements in recorded micturition and urodynamic variables, e.g. at a dosage of 2 mg twice daily, the frequency of micturition, episodes of incontinence and pad use were reduced by 20%, 46% and 29%, respectively, while the volume at first contraction increased by 89 mL. The 4 mg dosage was associated with a large increase in residual urinary volume and an increased incidence of dry mouth. The incidence of adverse events (mainly mild or moderate antimuscarinic effects) was comparable with placebo at tolterodine dosages of < or = 2 mg. No serious adverse events were observed and tolterodine had no clinically significant impact on electrocardiographic or laboratory findings.\n The results indicate that tolterodine offers an effective treatment for the symptoms of detrusor instability. The optimum dosage appears to be 1-2 mg twice daily.", "Unstable bladder is a frequent syndrome in women and is due in the most part because of detrusor involuntary contractions, mainly due to detrusor denervation, which produces voiding hypersensitivity and loss of cortical inhibition control, clinical manifestations are: frequency, nicturia, urgency and urge incontinence. Historically the most effective treatment has been muscular relaxing agents and anticholinergic agents. We present a prospective, double blind, cross, placebo control study to evaluate efficacy and tolerance of oxybutynin in women with unstable bladder. We included 44 adult women with unstable bladder, 22 unitially received oxybutynin 5 mg t.i.d. and 22 placebo 5 mg t.i.d. aleatory in both groups through 6 weeks, later wash-out period was performed and those women in which initially received oxybutynin were administered placebo and those women in which initially received placebo, were administered oxybutynin, for another six weeks. Five patients which initiated the study with oxybutynin abandoned the study, 2 of them for intolerance and 3 for unknown causes. Two women in which initially received placebo abandoned follow-up too. A total of 74 subjects (37 for each branch of study) had an age average of 51.7. Symptoms scoring decreased from 13 to 11 and 6 points with placebo and oxybutynin respectively (p = 0.001). The analog visual scale of symptoms decreased from 77% to 62.5% and 40% with placebo and oxybutynin respectively (p = 0.003). The overall rate of improvement evaluated through symptoms scoring was from 27% with placebo and 72.9% with oxybutynin (p = 0.000) and evaluated through analog visual scale of symptoms was from 40% with placebo and 78.3% with oxybutynin (p = 0.002). The vesical volume at first voiding sensation increased from 129 ml to 134 ml and 187 ml with placebo and oxybutynin respectively (p = 0.021) and the maximum cystometric capacity increased from 231 ml to 236 ml and 301 ml with placebo and oxybutynin respectively. The most frequent adverse effect in both groups was mouth dryness and it presented in 7 (19%) and 34 (91%) patients with placebo and oxybutynin respectively (p = 0.000). Only 5 of 44 patients (11.3%) with oxybutynin and 2 of 44 patients (4.4%) with placebo abandoned follow up (p = 0.14). We concluded that oxybutynin improve significantly the unstable bladder symptoms in women, possibly by increasing functional bladder capacity and decreasing voiding sensitivity, with good tolerance of mouth dryness in the majority of patients.", "The results of a double-blind controlled trial using oxybutynin chloride in 30 patients are described. Twenty-three patients completed the study; 17 of these had symptomatic improvement and 9 patients had urodynamic improvement. Seventeen patients had significant side effects.", "The effect of the anticholinergic agent, emepronium bromide (Cetiprin), was studied in a double blind crossover study of a group of elderly patients with urinary incontinence and uninhibited bladder contractions during cystometry. There was no statistically significant difference between the subjective effect of emepronium bromide and that of placebo, and no change in the cystometric parameters. The overall subjective cure or improvement rate was 79%. The effect of anticholinergic drugs in the treatment of urinary incontinence in elderly patients with uninhibited bladder contractions might to some extent be due to an improvement in the patients' understanding and acceptance of the bladder disorders.", "To examine the efficacy and tolerability of antimuscarinic therapy in women with urge-predominant mixed incontinence.\n This was a double-blind, randomized, placebo-controlled trial comprising 854 women with urge-predominant mixed incontinence, including urge incontinence (five or more episodes per week), urinary frequency (eight or more micturitions on average in 24 hours), and urgency in combination with stress incontinence. Women received 8 weeks of treatment with tolterodine tartrate extended-release (ER) 4 mg or placebo once daily. The outcome measures included urge incontinence episodes per week, stress incontinence episodes per week, micturition frequency per 24 hours, urgency episodes per 24 hours, volume voided per micturition, patient perception of bladder condition, and assessment of treatment benefit.\n After 8 weeks, tolterodine ER produced a statistically significant decrease in the weekly urge incontinence episodes compared with placebo (-12.3 versus -8.0; P <0.0001). Other micturition variables improved significantly more with tolterodine ER. No difference was found between treatment groups regarding the change in the number of stress incontinence episodes. A significantly greater proportion of patients receiving tolterodine ER than those receiving placebo reported improvement in bladder condition (61% versus 46%; P <0.001) and treatment benefit (76% versus 55%; P <0.001). After 8 weeks, the tolterodine ER group had experienced statistically significant improvements compared with the placebo group in 9 of 10 quality-of-life domains. The frequency of adverse events was similar between treatment groups.\n Tolterodine ER is an effective treatment of urge urinary incontinence, frequency, and urgency in women with concomitant stress urinary incontinence. The efficacy of tolterodine ER in reducing urge incontinence episodes was unaffected by the presence of stress incontinence. The results of this study support the first-line use of antimuscarinic therapy to treat the urge incontinence component of urge-predominant mixed incontinence.", "To evaluate the efficacy, tolerability and safety of darifenacin, a once-daily M3) selective receptor antagonist (M3 SRA), in patients with overactive bladder (OAB).\n This multicentre, double-blind, placebo-controlled, parallel-group study enrolled 561 patients (19-88 years; 85% female) with OAB symptoms for >6 months, and included some patients with prior exposure to antimuscarinic agents. After washout and a 2-week placebo run-in, patients were randomised (1:4:2:3) to once-daily oral darifenacin controlled-release tablets (3.75 mg [n=53], 7.5 mg [229] or 15 mg [n=115]) or matching placebo (n=164) for 12 weeks. Patients recorded daily incontinence episodes, micturition frequency, bladder capacity (mean volume voided), frequency of urgency, severity of urgency, incontinence episodes resulting in change of clothing or pads and nocturnal awakenings due to OAB using an electronic diary during weeks 2, 6 and 12 (directly preceding clinic visits). Tolerability data were evaluated from adverse event reports.\n Darifenacin 7.5 mg and 15 mg had a rapid onset of effect, with significant improvement compared with placebo being seen for most parameters at the first clinic visit (week 2). This effect was sustained through week 12. At this time the number of incontinence episodes per week was reduced from baseline by 67.7% with darifenacin 7.5 mg and 72.8% with darifenacin 15 mg compared with 55.9% with placebo (p=0.010 and p=0.017, respectively, versus placebo). The 3.75 mg group (null dose arm) was included for proof of concept of dose flexibility, therefore formal sample sizing and statistical analysis were not performed for this group. Darifenacin 7.5 mg and 15 mg, respectively, were significantly superior to placebo for improvements in micturition frequency (p<0.001, p<0.001), bladder capacity (p<0.040, p<0.001), frequency of urgency (p<0.001, p=0.005), severity of urgency (p<0.001, p=0.002) and number of incontinence episodes leading to a change in clothing or pads (p<0.001, p=0.002). There was no significant reduction in nocturnal awakenings due to OAB. The most common adverse events were mild-to-moderate dry mouth and constipation. However, no patients withdrew from the study as a result of dry mouth and discontinuation related to constipation was rare (0.6% placebo versus 0.9% darifenacin). In addition, there was a low need for laxative use, with no difference between the darifenacin groups and those taking placebo. There were no reports of blurred vision and the CNS and cardiac safety profile was comparable to placebo.\n Darifenacin significantly improves the major symptoms of OAB. No significant CNS (primarily M1-receptor mediated) adverse events or cardiac (primarily M2-receptor mediated) adverse events were identified in this study, as may be predicted from the M3 selective receptor profile of darifenacin.", "Twenty-four incontinent elderly institutionalized subjects with detrusor instability participated in a double-blind placebo-controlled trial of oxybutynin chloride. Patients were randomly assigned to oral oxybutynin 5 mg or placebo twice daily. Administration continued for 8 days; a 6-day washout period was followed by the alternative treatment. Incontinence was recorded using a bedside electronic monitor. Four subjects withdrew because of side-effects before completing the trial. There were no clinically significant differences between the oxybutynin and placebo treatments. Both groups experienced side-effects, of which dry mouth was the commonest. Thus, oxybutynin does not appear to be more effective than placebo for the treatment of incontinence in the presence of detrusor instability in elderly institutionalized people.", "To describe changes in bladder function and voiding frequency associated with behavioral and drug treatment for urge incontinence and to examine whether these variables mediate the positive effects of treatment on the frequency of incontinence.\n Randomized, double-blinded, placebo-controlled, clinical trial. Eligible patients were stratified according to type of incontinence (urge only vs mixed urge and stress) and severity of incontinence (frequency of accidents as documented in bladder diary).\n University-based outpatient geriatric medicine clinic.\n One hundred five ambulatory, nondemented, community-dwelling women; mean age 67.0 (range 55-91); 98% white, 2% African American.\n Four sessions (over 8 weeks) of biofeedback-assisted behavioral training, drug treatment with individually-titrated oxybutynin chloride, or a placebo control condition.\n Two-channel cystometry was performed to determine threshold volumes for first desire to void (FDV), strong desire to void (SDV), bladder capacity, and the volume at which detrusor instability (DI) or leakage occurred, before randomization and after completion of treatment. Two-week bladder diaries were used before and after treatment to document episodes of incontinence and voiding frequency.\n Bladder capacity increased by 68.9 mL in the oxybutynin group (P <.001) and 17.3 mL in the behavior group and decreased 6.0 mL in the control group. SDV increased 69.9 mL in the oxybutynin group (P <.001), 40.5 in the behavior group (P <.05), and 7.8 mL in the control group. FDV increased by 44.4 mL in the oxybutynin group (P <.001), 18.8 mL in the behavior group, and 8.9 mL in the control group. One of seven patients who presented with DI (12.0%) resolved in the behavior group, seven of eight (87.5%) resolved in the oxybutynin group, and seven of 12 (58.3%) resolved in the control group. These differences were not statistically significant. Voiding frequency was significantly reduced after treatment in both the behavior and the oxybutynin group. Behavioral training resulted in a mean 82.3% reduction in frequency of accidents, oxybutynin (final doses 2.5 mg daily to 5 mg three times a day) resulted in a mean 78.3% reduction, and the control condition resulted in a mean 51.5% reduction (P =.002). Although oxybutynin and behavioral treatment were both effective, and oxybutynin increased SDV and bladder capacity, the structural equation modeling did not demonstrate that the clinical improvement was mediated through the effects of these treatments on urodynamic or voiding frequency measures.\n Studies using more-complex urodynamics and studies with larger sample sizes are needed to better characterize changes in bladder function and explore other urodynamic changes that may accompany treatment. In addition, other factors, both physiological and behavioral, need to be explored as mechanisms by which conservative therapies improve urge incontinence.", "To evaluate the efficacy, safety, and tolerability of a new, once-daily extended-release (ER) formulation of tolterodine in treating overactive bladder in older (> or =65) and younger (<65) patients.\n A 12-week double-blind, placebo-controlled clinical trial.\n An international study conducted at 167 medical centers.\n One thousand fifteen patients (43.1% aged > or =65) with urge incontinence and urinary frequency.\n Patients were randomized to treatment with tolterodine ER 4 mg once daily (qd) (n = 507) or placebo (n = 508) for 12 weeks.\n Efficacy, measured with micturition charts (incontinence episodes, micturitions, volume voided per micturition) and subjective patient assessments, safety, and tolerability endpoints were evaluated, relative to placebo, according to two age cohorts: younger than 65 and 65 and older.\n Mean age in the older and younger patient cohorts was 74 (range 65-93) and 51 (range 20-64), respectively. Compared with placebo, significant improvements in micturition chart variables with tolterodine ER showed no age-related differences. Irrespective of age, significantly more tolterodine ER recipients than placebo recipients reported an improvement in urgency symptoms. After 12 weeks of treatment with tolterodine ER, a fivefold increase in the percentage of patients able to finish tasks before voiding in response to urgency was noted in both age groups (<65: from 6.5-32.8%, > or =65: from 5.1-26.2%). Tolterodine ER recipients, irrespective of age, also had significant improvements in their bladder condition than did placebo recipients. Overall, a greater percentage of patients, irrespective of age, perceived any benefit with tolterodine ER than with placebo (P <.001). Dry mouth (of any severity) was the most common adverse event in both the tolterodine ER and placebo treatment arms, irrespective of age (<65: ER 22.7%, placebo 8.1%; > or =65: ER 24.3%, placebo 7.2%). Few patients (<2%) experienced severe dry mouth. No central nervous system, visual, cardiac (per electrocardiogram), or laboratory safety concerns were noted. Withdrawal rates due to adverse events on tolterodine ER 4 mg qd were comparable in the two age cohorts (<65: 5.5%; > or =65: 5.1%; P =.87).\n The new, once-daily ER formulation of tolterodine is efficacious, safe, and well tolerated in the treatment of patients with symptoms of overactive bladder, irrespective of age.", "Urinary incontinence is a common condition caused by many factors with several treatment options.\n To compare the effectiveness of biofeedback-assisted behavioral treatment with drug treatment and a placebo control condition for the treatment of urge and mixed urinary incontinence in older community-dwelling women.\n Randomized placebo-controlled trial conducted from 1989 to 1995.\n University-based outpatient geriatric medicine clinic.\n A volunteer sample of 197 women aged 55 to 92 years with urge urinary incontinence or mixed incontinence with urge as the predominant pattern. Subjects had to have urodynamic evidence of bladder dysfunction, be ambulatory, and not have dementia.\n Subjects were randomized to 4 sessions (8 weeks) of biofeedback-assisted behavioral treatment, drug treatment (with oxybutynin chloride, possible range of doses, 2.5 mg daily to 5.0 mg 3 times daily), or a placebo control condition.\n Reduction in the frequency of incontinent episodes as determined by bladder diaries, and patients' perceptions of improvement and their comfort and satisfaction with treatment.\n For all 3 treatment groups, reduction of incontinence was most pronounced early in treatment and progressed more gradually thereafter. Behavioral treatment, which yielded a mean 80.7% reduction of incontinence episodes, was significantly more effective than drug treatment (mean 68.5% reduction; P=.04) and both were more effective than the placebo control condition (mean 39.4% reduction; P<.001 and P=.009, respectively). Patient-perceived improvement was greatest for behavioral treatment (74.1% \"much better\" vs 50.9% and 26.9% for drug treatment and placebo, respectively). Only 14.0% of patients receiving behavioral treatment wanted to change to another treatment vs 75.5% in each of the other groups.\n Behavioral treatment is a safe and effective conservative intervention that should be made more readily available to patients as a first-line treatment for urge and mixed incontinence.", "To evaluate the effect of once-daily, extended-release tolterodine on urinary urgency in patients with overactive bladder.\n Patients with urinary frequency (eight or more micturitions per 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral treatment with tolterodine extended release 4 mg once daily (n=398) or placebo (n=374) for 12 weeks. Efficacy was assessed by use of patient perception evaluations.\n The results presented are a secondary analysis of this double-blind, placebo-controlled study. Of patients treated with tolterodine extended release, 44% reported improved urgency symptoms (compared with 32% for placebo), and 62% reported improved bladder symptoms (placebo, 48%) (both P<.001 compared with placebo). The odds of reducing urgency and improving bladder symptoms were 1.68 and 1.78 times greater, respectively, for patients in the tolterodine extended release group than for patients receiving placebo. In response to urgency, there was a more than six-fold increase in the proportion of patients able to finish a task before voiding in the tolterodine extended release group. The proportion of patients unable to hold urine upon experiencing urgency was also decreased by 58% with tolterodine, compared with 32% with placebo (P<.001). The proportion of patients reporting \"much benefit\" from treatment was greater for tolterodine extended release than for placebo (43% versus 24%; P<.001). The only adverse events with an incidence of greater than 5% were dry mouth, headache, and constipation, with only dry mouth markedly more frequent with tolterodine than with placebo.\n Tolterodine extended release has demonstrable efficacy in reducing the severity of urinary urgency and is associated with improvements in overactive bladder symptoms that are meaningful to patients.", "In this phase 3 trial we assessed the efficacy of solifenacin 5 mg and 10 mg daily in patients with symptoms related to overactive bladder. In addition, we assessed the safety and acceptability of solifenacin.\n The study was a multicenter, multinational, randomized, double-blind, placebo controlled trial. Patients were randomized to 12-week once daily treatment with solifenacin 5 mg, solifenacin 10 mg or placebo. The primary efficacy variable was changed from baseline to study end point in mean number of micturitions per 24 hours. Secondary efficacy variables included changes from baseline in mean number of urgency, nocturia and incontinence episodes per 24 hours, and mean volume voided per micturition.\n Compared with changes obtained with placebo (-1.59), micturitions per 24 hours were statistically significantly decreased with solifenacin 5 mg (-2.37, p = 0.0018) and solifenacin 10 mg (-2.81, p = 0.0001). A statistically significant decrease was observed in the number of incontinence episodes with both solifenacin doses (5 mg, p = 0.002 and 10 mg, p = 0.016). This effect was also seen for episodes of urge incontinence (5 mg, p = 0.014 and 10 mg, p = 0.042). Of patients reporting incontinence at baseline, fully 50% achieved continence after treatment with solifenacin. Episodes of nocturia were statistically significantly decreased in patients treated with solifenacin 10 mg (-0.71, -38.5%) versus placebo (-0.52, -16.4%, p = 0.036). Episodes of urgency were statistically significantly reduced with solifenacin 5 mg (-2.84, -51%, p = 0.003) and solifenacin 10 mg (-2.90, -52%, p = 0.002). Mean volume voided per micturition was statistically significantly increased with both solifenacin doses (p = 0.0001). Treatment with solifenacin was well tolerated. Dry mouth, mostly mild in severity, was reported in 7.7% of patients receiving solifenacin 5 mg and 23% receiving solifenacin 10 mg (vs 2.3% with placebo).\n In this study treatment with solifenacin 5 mg and 10 mg once daily significantly improved all the major symptoms of overactive bladder including frequency, urgency and incontinence. Solifenacin 10 mg also decreased the frequency of nocturia. Solifenacin therapy was associated with a favorable tolerability profile and a low incidence of dry mouth, especially at the 5 mg starting dose.", "Trospium chloride is an anticholinergic agent with predominantly peripheral nonselective antimuscarinic activity lacking central nervous system effects. It has no known drug-drug interactions, an advantage for patients taking many medications. Because these qualities may provide added benefit when treating patients with symptoms associated with overactive bladder (OAB) and urge incontinence, we studied the effectiveness of trospium in treating these conditions.\n Patients with OAB with urge incontinence were randomized 1:1 to 20 mg trospium twice daily or placebo in this 12-week, multicenter, parallel, double-blind, placebo controlled trial. Dual primary end points were change in average number of toilet voids and change in urge incontinent episodes per 24 hours. Secondary efficacy variables were change in average of volume per void, voiding urge severity, urinations during day and night, time to onset of action and change in Incontinence Impact Questionnaire.\n A total of 523 patients were entered at 51 sites. Trospium significantly decreased average frequency of toilet voids and urge incontinent episodes compared to placebo. It significantly increased average volume per void, and decreased average urge severity and daytime frequency. All effects occurred by week 1 and all were sustained throughout the study. Nocturnal frequency decreased significantly by week 4 and Incontinence Impact Questionnaire scores improved at week 12. Trospium was well tolerated.\n Trospium was found to have sustained effectiveness beginning at the end of week 1 in decreasing the number of voids, urge incontinent episodes, total daily micturitions and urge severity, and in increasing volume per void. It also improved symptoms of OAB and quality of life.", "In a multicentre placebo-controlled double-blind study 61 patients with spinal cord injuries and detrusor hyperreflexia were treated: 20 mg trospium chloride was given twice daily over a period of 3 weeks. Pre- and posttreatment urodynamic measurements demonstrated large improvements in maximum cystometric capacity (mean = 138.1 ml), decreased maximum detrusor pressure (mean = -37.8 cm H2O) and an increase in compliance (mean = 12.1 ml/cm H2O) in the treatment group. Urodynamic parameters in the placebo group remained substantially unchanged. Comparisons between the two groups revealed highly significant differences for these parameters (all, p less than 0.001). No effect on maximum flow rate and residual urine was detected in either group. The incidence of spontaneously reported side-effects was extremely low and comparable for both groups.", "To investigate the clinical safety and efficacy of two dosages of tolterodine in older patients with symptoms attributable to overactive bladder.\n Randomized, double-blind, placebo-controlled, parallel-group, multinational, phase III study.\n Incontinence, older care, urological, and urogynecological clinics in the United Kingdom, France, and the Republic of Ireland.\n One hundred and seventy-seven older patients (age > or =65 years) with symptoms of urinary urgency, increased frequency of micturition (> or =8 micturitions/24 hours), and/or urge incontinence (> or =1 episode/24 hours).\n Tolterodine 1 mg or 2 mg twice daily (bid), or placebo, for 4 weeks.\n Safety and tolerability were evaluated through spontaneously reported adverse events, electrocardiogram, and blood pressure measurements. Efficacy was assessed using micturition diary variables: mean change from baseline in frequency of micturition and number of incontinence episodes/24 hours.\n The mean age of the patient population was 75 years. Overall, > or =87% of patients completed the study. Neither dosage of tolterodine was associated with serious drug-related adverse events during the study. No cardiac arrythmogenic events were noted. Dry mouth (mild to moderate intensity) was the most common adverse event in both the placebo and tolterodine treatment groups. Three percent of patients in the tolterodine 2 mg bid group discontinued treatment because of dry mouth, compared with 2% of placebo-treated patients. Compared with placebo, statistically significant decreases in micturition frequency were apparent in both tolterodine treatment groups. Furthermore, patients treated with tolterodine 2 mg bid had statistically significant decreases in urge incontinence episodes/24 hours and increases in volume voided per micturition compared with placebo.\n Tolterodine (taken for 4 weeks) is safe and shows efficacy, particularly at a dosage of 2 mg bid, in the treatment of older patients with urinary symptoms attributable to overactive bladder.", "To compare the efficacy and safety of an oxybutynin transdermal delivery system (OXY-TDS) and oral, long-acting tolterodine (TOL-LA) with placebo in previously treated patients with urge or mixed urinary incontinence.\n After withdrawal of their current antimuscarinic therapy, 361 adult patients were randomized to 12 weeks of double-blind, double-dummy treatment with twice weekly OXY-TDS 3.9 mg/day, daily TOL-LA 4 mg, or placebo. Evaluations included change from baseline in patient urinary diary symptoms, incontinence-specific quality of life, and safety.\n OXY-TDS 3.9 mg/day and TOL-LA 4 mg/day significantly reduced the number of daily incontinence episodes (median change -3 OXY-TDS and -3 TOL-LA versus -2 placebo; P <0.05), increased the average void volume (median change 24 and 29 mL versus 5.5 mL, P <0.01), and improved quality of life (incontinence impact questionnaire [IIQ] total score, P <0.05; Urogenital Distress Inventory Irritative Symptom subscale, P <0.05) compared with placebo. The most common adverse event for OXY-TDS was localized application site pruritus (14% versus 4% placebo) accompanied by a low incidence of systemic side effects (eg, dry mouth 4.1%). Anticholinergic adverse events occurred with greatest frequency during TOL-LA treatment (dry mouth 7.3% versus 1.7% placebo, P <0.05).\n OXY-TDS and TOL-LA are effective and comparable treatments for patients with urge and mixed incontinence. OXY-TDS improves systemic safety with regard to anticholinergic side effects. Local skin irritation occurs in some OXY-TDS patients.", "To assess the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence in a randomized, double-blind placebo-controlled clinical trial.\n In all, 366 patients (149 on propiverine, 145 oxybutynin and 72 placebo, ratio 2:2:1) with urgency and urge incontinence were recruited in 32 study centres. Propiverine (group 1, 15 mg three times daily), oxybutynin (group 2, 5 mg twice daily) or placebo (group 3) were administered for 4 weeks, using the double-dummy technique. The dosages were selected specifically to compare the tolerability profile of propiverine with the commonly used therapeutic dosage of oxybutynin. Tolerability was assessed by directly questioning the patients about adverse events at four visits (V-1 before and V0 after a 1-week 'washout' period, V1 after 1 week and V4 after 4 weeks of treatment) during a 5-week surveillance period, and by tolerability ratings of the physicians. Efficacy was assessed using urodynamics at V0 and V4, evaluating the cystometric bladder capacity at maximal and first desire to void, and postvoid residual urine, according to the criteria of the International Continence Society. Additionally, a voiding protocol, overall assessment of clinical symptomatology and efficacy ratings by the physicians were documented.\n A remarkably high percentage of adverse events was reported in the washout period (VO: 13%, 16% and 18% in groups 1-3, respectively). At V4, the clinically most relevant symptom (dry mouth) occurred in 53% of patients in group 1, in 67% of group 2 and in 28% of group 3. Furthermore, dry mouth was less severe in group 1 than group 2. In contrast to groups 2 and 3, only patients in group 1 showed increasing tolerability during the treatment (from V1 to V4). These tolerability results were further supported by the overall tolerability assessment ('very good' or 'good' tolerability in 67% of group 1, in 59% of group 2 and in 83% of group 3). The urodynamic assessment of efficacy (comparing V0 and V4) showed a statistically significant increase in the mean (sd) maximal cystometric bladder capacity in group 1, being 222 (77) mL at V0 and 311 (125) mL at V4, an increase of 89 (108) mL, and in group 2, at 226 (75) mL and 322 (123) mL, an increase of 96 (106) mL, compared with group 3, at 211 (77) mL and 263 (93) mL, an increase of only 52 (92) mL. The cystometric bladder capacity at first desire to void also increased in group 1 (93 to 160 mL) and group 2 (89 to 160 mL), whereas in group 3 there were only minor changes (93 to 120 mL). Changes in the residual urine volume within and between the treatment groups were minimal and clinically irrelevant. The overall assessment of efficacy showed significant differences between the drugs when compared with placebo.\n Propiverine is a safe and effective drug in the treatment of urgency and urge incontinence; it is as effective as oxybutynin, but the incidence of dry mouth and its severity is less with propiverine than with oxybutynin. The availability of alternative pharmacotherapeutics such as propiverine should reduce the therapeutic failure rate and improves the success rate in the treatment of patients suffering from urgency and urge incontinence.", "Overactive bladder (OAB) has a significant impact on a patient's health-related quality of life (HRQoL). This study assessed the HRQoL of Japanese OAB patients following 12 weeks' treatment with tolterodine extended release (ER) or oxybutynin. A total of 293 patients with symptoms of OAB were randomized for treatment with tolterodine ER 4 mg once daily (n=114), oxybutynin 3 mg three times daily (n=122) or a placebo (n=57). Treatment efficacy and safety assessments were made over the 12-week period. HRQoL was assessed using the King's Health Questionnaire (KHQ). Patients receiving tolterodine ER or oxybutynin showed a significant (P<0.05) improvement in the Incontinence Impact, Role Limitations and most other KHQ domains compared with the placebo. These changes in HRQoL corresponded with significant (P<0.05) improvements in micturition diary variables for patients receiving tolterodine ER and oxybutynin compared with placebo. Our findings demonstrate that Japanese OAB patients receiving tolterodine ER or oxybutynin experienced overall improvement in their quality of life.", "Oxybutynin hydrochloride (3 mg) was compared with placebo by randomised, double-blind crossover trial in 53 females with idiopathic detrusor instability. Symptoms were cured or markedly improved in 60% of patients on oxybutynin and 2.3% on placebo. During the first treatment period, oxybutynin reduced the frequency of voiding by 35%, compared with 9% for placebo. Oxybutynin gave a significantly greater improvement than placebo in volume at the first desire to void (70 ml increase versus 7.7 ml), maximum filling-phase detrusor pressure (17 cm H2O reduction versus no benefit) and cystometric capacity (104 ml increase versus 7.0 ml). A marked oxybutynin carry-over effect was seen during the second treatment period. Side effects from the 3 mg dose of oxybutynin caused 7.5% of subjects to discontinue therapy.", "To assess in a phase 3a trial the efficacy of solifenacin succinate, a once-daily oral antimuscarinic agent in development at 5-mg and 10-mg dosage strengths, for the treatment of overactive bladder (OAB) (Yamanouchi Pharmaceutical Co. Ltd, Tokyo, Japan) compared with placebo in patients with symptoms of OAB, i.e. urgency, incontinence, and frequency, with additional objectives being to assess the safety and tolerability of solifenacin and to compare the efficacy and safety of solifenacin with tolterodine 2 mg twice daily.\n The study was an international, multicentre, randomized, double-blind, tolterodine- and placebo-controlled trial conducted at 98 centres. Adult patients with symptomatic OAB for > or = 3 months were eligible; after a single-blind 2-week placebo run-in period patients were randomized equally to a 12-week double-blind treatment with either tolterodine 2 mg twice daily, placebo, solifenacin 5 mg or 10 mg once daily. Efficacy variables included change from baseline in the mean number of urgency, incontinence and urge incontinence episodes, and change from baseline in voids/24 h and mean volume voided/void.\n In all, 1281 patients were enrolled, 1081 randomized and 1077 treated; 1033 were evaluated for efficacy. Compared with placebo, the change from baseline (-1.41, -32.7%) in the mean number of urgency episodes per 24 h was statistically significantly lower with solifenacin 5 mg (-2.85, -51.9%) and 10 mg (-3.07, -54.7%; both P < 0.001), but not with tolterodine (-2.05, -37.9%; P = 0.0511). There was a statistically insignificant decrease in episodes of incontinence with tolterodine (-1.14; P = 0.1122) but a significant decrease in patients treated with solifenacin 5 (-1.42; P = 0.008) and 10 mg (-1.45; P = 0.0038). Compared with placebo (-1.20, -8.1%) the mean number of voids/24 h was significantly lower in patients receiving tolterodine (-1.88, -15%; P = 0.0145), solifenacin 5 (-2.19, -17%) and 10 mg (-2.61, -20%; both P < 0.001). The mean volume voided/void was also significantly higher with all three active treatments (P < 0.001). Solifenacin was well tolerated; compared with placebo (4.9%), dry mouth (the most common side-effect), mostly mild, was reported in 18.6% of patients receiving tolterodine, 14.0% receiving 5 mg and 21.3% receiving 10 mg solifenacin.\n Solifenacin 5 and 10 mg once daily improved urgency and other symptoms of OAB, and was associated with an acceptable level of anticholinergic side-effects. Solifenacin demonstrated significantly favourable efficacy to side-effect ratio in treating symptomatic OAB.", "Idiopathic detrusor instability is a common cause of incontinence in the elderly for which anticholinergic agents are regularly prescribed. Oxybutynin chloride combines anticholinergic action with direct muscle relaxant properties. We performed a double blind placebo controlled fixed dose cross over study of oxybutynin chloride in post-menopausal women suffering from detrusor instability. We found oxybutynin chloride significantly more effective than placebo at reducing the symptoms of urgency and urge incontinence and more effective at reducing the height of the highest unstable detrusor contraction. This was at the expense of an increased residual urine and considerable side effects.", "We evaluated the efficacy, patient acceptability and side effect profile of tolterodine, a new antimuscarinic agent for treating bladder overactivity.\n In our randomized, placebo controlled, parallel group study 123, 129 and 64 patients 18 years old or older with proved detrusor overactivity (idiopathic detrusor instability or detrusor hyperreflexia) were randomized to receive 1 or 2 mg. tolterodine, or placebo, respectively, twice daily for 12 weeks. Main outcome measures were number of voids per 24 hours, urine volume per void and episodes of urge incontinence per 24 hours on a frequency-volume chart with detailed recording of side effects.\n After 12 weeks of treatment mean number of voids per 24 hours plus or minus standard deviation decreased from 11.2 +/- 3.1 to 9.0 +/- 2.6 with the 2 mg. dosage (p = 0.0045 versus placebo). At this dose mean urine volume per void increased from 155 +/- 52 to 190 +/- 70 ml. (p <0.0001 versus placebo), while mean number of incontinence episodes per 24 hours decreased from 3.6 +/- 4.0 to 1.8 +/- 3.1 (p = 0.19 versus placebo). Similar efficacy was observed in patients receiving the 1 mg. dose. Severe dry mouth was reported by only 2, 1 and 2% of patients given the 1 and 2 mg. dose, and placebo, respectively. There was no clinical or electrocardiographic evidence of significant cardiac adverse events.\n Tolterodine administration resulted in a significant decrease in the frequency of voiding and improved voided volume but it was seldom associated with troublesome or severe side effects.", "The aim of this study was to examine the efficacy of oxybutynin plus bladder training in the treatment of detrusor instability in frail elderly patients living independently in the community. It was a randomized, double-blind, placebo-controlled parallel-group trial of oxybutynin in 57 elderly patients (mean age 82.2, SD 6.06), with frequency and incontinence due to detrusor instability. After a 2-week run-in period patients received a bladder training and drug or placebo for the next 6 weeks. Outcome measures were changes in frequency and incontinence, recorded throughout on diary charts, and subjective evaluation of symptoms ('better'/'not better', and using a four-point scale 'cure' to 'no change'). Oxybutynin was superior to placebo in reducing daytime frequency [95% confidence interval (CI) of difference in change in frequencies totalled over 14 days was -27.0, -6.0; p = 0.003] and in producing subjective benefit (at day 29 only), when 24/28 (86%) patients on oxybutynin described benefit compared with 16/29 (55%) on placebo (p = 0.02). There was no difference between the groups in reduction of incontinent episodes. The median dose of oxybutynin titrated for therapeutic effect was 5 mg/day, and for placebo 10 mg/day (CI of difference 0.001, 5.001; p = 0.05). Side-effects reported were of similar frequency (50%) in the two groups. We conclude that oxybutynin with bladder training is superior to bladder training alone in reducing frequency due to detrusor instability in very elderly people living at home.", "The Authors carried out a random double-blind trial on 30 patients affected by idiopathic urge incontinence with oxybutynin chloride (15 mg/die) and placebo for two 20 day therapeutical cycles. The 24 patients who completed the trial oxybutynin chloride induced statistically significant effects--compared to placebo too--both on the subjective symptoms (reduction or disappearance of the urgency in 14 cases - 60.8% - and of urge incontinence in 16 cases - 76.1%) and on the objective symptoms showed by cystomanometry (increased bladder capacity at the FD and VSD in 14 and 15 cases, respectively; absence of involuntary contraction in 9 cases and normal or reduced detrusor pressure at the VSD in 13 out of 16 cases). Improvements, though less significant, were also obtained with the placebo.", "Clinical efficacy and adverse effects of oxybutynin and propantheline in the treatment of symptoms related to detrusor hyperactivity were studied in a randomized, controlled, double-blind multicenter trial. Of 169 patients entered into the study 154 were evaluable for statistical analysis. Mean grade of improvement (visual analogue scale) was significantly higher with oxybutynin (58.2%) versus propantheline (44.7%) and placebo (43.4%). Mean bladder volume at first involuntary cystometric contraction was significantly increased with oxybutynin (+57.0 ml.) versus placebo (-9.7 ml.). Mean maximum cystometric bladder capacity was also significantly increased with oxybutynin (+80.1 ml.) versus placebo (+22.5 ml.). Rate of inquired possible adverse effects was significantly higher for oxybutynin (63%) versus propantheline (44%) and placebo (33%). However, only 5 patients dropped out of the study because of adverse effects (oxybutynin 2 and propantheline 3). No serious or lasting adverse effects were encountered with dryness of the mouth being the major complaint. Oxybutynin has statistically significant effects on subjective symptoms and objective urodynamic parameters in patients with detrusor hyperactivity compared to propantheline." ]

[ "20427749" ]

[ "A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis." ]

[ "Low vitamin D status has been associated with multiple sclerosis (MS) prevalence and risk, but the therapeutic potential of vitamin D in established MS has not been explored. Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical, immunologic, and clinical outcomes in patients with MS prospectively.\n An open-label randomized prospective controlled 52-week trial matched patients with MS for demographic and disease characteristics, with randomization to treatment or control groups. Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [25(OH)D] rapidly and assess tolerability, followed by 10,000 IU/day (12 weeks), and further downtitrated to 0 IU/day. Calcium (1,200 mg/day) was given throughout the trial. Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups. Secondary endpoints included 25(OH)D and other biochemical measures, immunologic biomarkers, relapse events, and Expanded Disability Status Scale (EDSS) score.\n Forty-nine patients (25 treatment, 24 control) were enrolled [mean age 40.5 years, EDSS 1.34, and 25(OH)D 78 nmol/L]. All calcium-related measures within and between groups were normal. Despite a mean peak 25(OH)D of 413 nmol/L, no significant adverse events occurred. Although there may have been confounding variables in clinical outcomes, treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls.\n High-dose vitamin D (approximately 10,000 IU/day) in multiple sclerosis is safe, with evidence of immunomodulatory effects.\n This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation. The trial, however, lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures (relapses and Expanded Disability Status Scale scores), providing only Class level IV evidence for these outcomes." ]

[ "12616888", "1803333", "15910477", "5280979" ]

[ "Capping carious exposed pulps with potassium nitrate, dimethyl isosorbide, polycarboxylate cement.", "A clinical and histological evaluation of conservative pulpal therapy in human teeth.", "Endodontic complications after plastic restorations in general practice.", "The efficacy of pulp capping materials. A comparative trial." ]

[ "nan", "Three intermediary base materials, a zinc oxide-eugenol (Cavitec) and two calcium hydroxide liners (Life and Dycal), were selected at random for use as a base beneath amalgam or composite restorations on humans following complete caries removal. Life and Dycal, selected at random, were also used as direct and indirect pulp capping agents as clinically indicated. Clinical evaluations of signs and symptoms were made before treatment and at one-week, six-month, and one-year intervals following treatment. Histological evaluations were performed on three complete caries removal teeth and 18 direct pulp capping teeth six months following treatment. No significant differences in clinical symptomatology resulted between the materials in the complete caries removal group or the indirect and direct pulp capping groups.", "To test the hypothesis that dentine and pulp protection by conditioning-and-sealing is no less effective than using a conventional calcium hydroxide lining.\n A cohort of healthy adults requiring a new or replacement restoration in a posterior tooth was recruited in six general practices. All procedures received local Ethics Committee approval. Exclusion criteria included signs and symptoms of pulp necrosis or inflammation, and patients unable to commit to a long-term trial. Cavity preparations were randomized to receive a calcium hydroxide lining or conditioning-and-sealing with a smear-removing bonding system. Choice of bulk restorative material (composite resin or amalgam) was at the discretion of the dentist. The key outcome measure was evidence of pulpal breakdown identified at unscheduled (emergency) or scheduled recall examinations. Postoperative sensitivity was recorded on 100 mm VAS at 24 h, 4 days and 7 days. Pulp status was assessed at 6, 12, 24 and 36 month recall, and at any emergency recall appointment. The relationship between pre-treatment and treatment variables and pulp breakdown was assessed by logistic regression (P = 0.05).\n A total of 602 teeth were recruited, with comparable numbers of cavities lined (288, 47.8%) or conditioned and sealed (314, 52.2%). The majority (492, 81.7%) were replacement restorations, and amalgam was the most common bulk restorative material (377, 62.6%). A total of 390 (64.8%) restored teeth were reviewed at 6 months, 307 (51%) at 12 months, 363 (60.3%) at 24 months, and 279 (46.3%) at 36 months post-restoration. Sixteen cases of pulp breakdown were identified within 36 months of restoration placement, 11 presenting as emergencies and five detected at routine recall examination. Logistic regression showed that preoperative pain, cavity treatment by lining or conditioning-and-sealing and the use of rubber dam isolation had no association with pulp breakdown. Pulp breakdown was associated with deep or pulpally exposed cavities (P < 0.001, odds ratio 7.8) and with composite rather than amalgam restorations (P = 0.001, odds ratio 2.13). Re-coding to identify teeth with pulp exposures revealed that pulpal exposure was the key determinant of adverse pulp outcomes (P < 0.0001, odds ratio 28.4) and that composite resin restorations were again more likely to be associated with pulp breakdown than amalgam (P = 0.017, odds ratio 3.92).\n Considered within the context of routine primary dental care: Dentists can be confident that pulps will be equally well protected from post-restorative breakdown up to 36 months by calcium hydroxide lining and conditioning-and-sealing with adhesive resins. Residual dentine thickness appears to be a key determinant of pulp responses after restorative dental treatment. In deep and pulpally exposed cavities in posterior teeth, composites were associated with more pulpal breakdown than amalgams.", "nan" ]

[ "10636350", "19793473", "11281486", "19621660", "9100679", "11103159", "10367869", "16910066", "12802644", "20575704" ]

[ "The need for antibiotic prophylaxis in elective laparoscopic cholecystectomy: a prospective randomized study.", "The role of prophylactic antibiotics in elective laparoscopic cholecystectomy.", "A reevaluation of antibiotic prophylaxis in laparoscopic cholecystectomy: a randomized controlled trial.", "Determinants of postoperative infection after laparoscopic cholecystectomy.", "Are prophylactic antibiotics required for elective laparoscopic cholecystectomy?", "A prospective, randomised trial of prophylactic antibiotics versus bag extraction in the prophylaxis of wound infection in laparoscopic cholecystectomy.", "Prophylactic antibiotics for elective laparoscopic cholecystectomy: are they necessary?", "Evaluation of the role of prophylactic antibiotics in elective laparoscopic cholecystectomy: a prospective randomized trial.", "A prospective randomized study of prophylactic antibiotics in elective laparoscopic cholecystectomy.", "Role of prophylactic antibiotics in laparoscopic cholecystectomy and risk factors for surgical site infection: a randomized controlled trial." ]

[ "The need for antibiotic treatment when performing elective laparoscopic cholecystectomy may not be as important as it is thought. This study assesses the real efficacy of antibiotic prophylaxis in elective laparoscopic cholecystectomy with respect to the postoperative infection rate.\n A prospective randomized study on the routine use of antibiotic prophylaxis in laparoscopic cholecystectomy.\n University teaching hospital, La Sapienza, Italy.\n Eighty-four patients randomly placed into 2 groups (A [n = 44] and B [n = 40]) immediately before undergoing laparoscopic cholecystectomy.\n Before anesthesia was administered, group A received intravenously 2 g of cefotaxime sodium diluted in 100 mL of isotonic sodium chloride solution; group B, 10 mL of isotonic sodium chloride solution in 100 mL of saline. A gallbladder bile sample for culture was withdrawn intraoperatively from all patients. In both groups, age, sex, weight, duration of surgery, presence of diabetes, American Society of Anesthesiologists patient classification score, preoperative autologous blood donation, antibiotic administration, intraoperative gallbladder rupture, findings from bile culture positive for bacteria, episodes of colic within 30 days before surgery, length of postoperative hospital stay, and number of septic complications were recorded. All data were correlated by univariate and multivariate analyses with the onset of septic phenomena.\n In group A, 3 cases of wound infection, 1 case of subhepatic abscess from bile leakage, and 1 case of urinary tract infection were observed; group B, 4 cases of wound infection, 1 case of bronchopneumonia, and 2 cases of urinary tract infection. Comparison of data showed no statistically significant difference between the groups. Findings from bile examination in patients with sepsis complications were positive in 5 patients in group A and in 6 in group B (P = .91). Multivariate analysis showed diabetes mellitus and colic episodes within 30 days before surgery as independent factors significantly associated to the onset of infectious complications.\n In elective laparoscopic cholecystectomy, antibiotic treatment did not seem to affect the incidence and severity of infections or the degree of bile contamination.", "Elective laparoscopic cholecystectomy has a low risk for infectious complications, but many surgeons still use prophylactic antibiotics. The aim of this prospective study was to investigate the necessity and test the efficacy of prophylactic antibiotics on postoperative infection complications in low-risk patients undergoing laparoscopic cholecystectomy.\n Low-risk patients were randomly placed into 2 groups: 68 patients (group 1) received cefazolin 1g intravenously after induction of anesthesia, and 76 patients (group 2) were not given prophylactic antibiotics. In both groups, septic complications were recorded and compared.\n Positive bile culture and gallbladder rupture did not significantly increase the rate of surgical site infections. In group 1, there were 3 (4.41%) cases of wound infection, 3 (4.41%) cases of pulmonary infections, and 1 (1.47%) case of urinary tract infection. In group 2, there were 2 (2.63%) cases of wound infection, 2 (2.63%) case of pulmonary infections, and 3 (3.95%) cases of urinary tract infection. No significant difference existed in the complication rates.\n Based on our data, the use of prophylactic antibiotics does not decrease the rate of postoperative infection complications and surgical-site infections and is not necessary in low-risk patients undergoing laparoscopic cholecystectomy.", "To assess the result of antibiotic prophylaxis in low-risk patients undergoing elective laparoscopic cholecystectomy with respect to the postoperative septic complications.\n One hundred and two low-risk patients were randomized into 1 of 2 treatment arms (1) cefazolin 1 g intravenously after induction of anesthesia (PA group) and (2) no prophylactic antibiotics (NONE group). Laparoscopic cholecystectomy was attempted in all cases. The patients were followed-up for postoperative septic complications for at least 30 days at the out-patient clinic or by telephone contact. In both groups, sex, age, weight, American Society of Anesthesiologists patient classification score, operative time, surgical techniques, number of port sites, intraoperative cholangiograms, intraoperative gallbladder rupture, postoperative hospital stay, and postoperative septic complications were compared. The statistical analysis of data performed by computer program SPSS 10.0 for Windows was based on the Independent-Samples T Test or the Pearson Chi-Square (2-sided).\n There was only one minor problem of superficial wound infection in the NONE group. Comparison of data showed no statistically significant difference between the groups.\n Antibiotic Prophylaxis may not be necessary in low-risk patients undergoing elective laparoscopic cholecystectomy.", "The aim of this study was to evaluate the effect of antibiotic prophylaxis on the development of infectious complications in laparoscopic cholecystectomy.\n A total of 208 patients undergoing elective laparoscopic cholecystectomy were randomized, double-blinded into one of two treatment arms: 1) cefazolin 1 g intravenously after induction of anesthesia and 2) no prophylactic antibiotics. The patients were followed-up for infectious complications for 30 days at the out-patient clinic. The data collected included age, sex, body mass index, ultrasonography findings, accompanying diseases, perforation during surgery, stone spillage, operation time, port of gallbladder delivery, suture material used for skin closure, preoperative and length of postoperative hospitalization, bile culture, pathology of the gallbladder, serum biochemical findings including alanine aminotransferase, aspartate aminotransferase, gammaglutamyl transpeptidase, bilirubin, alkaline phosphatase and glucose.\n Overall rate of infection was 3.36%. Four out of 105 patients who received antibiotics and 3 out of 103 patients who did not receive antibiotics developed infection. The difference was not statistically significant. Obesity and closing the skin with nylon sutures were found to be associated with increased rate of infectious complications.\n Cefazolin prophylaxis in low risk patients has no effect on postoperative infection rate in laparoscopic cholecystectomy.", "Some clinicians administer prophylactic antibiotics routinely before laparoscopic cholecystectomy, and the results of some of the studies in the literature support this practice. We conducted a prospective randomized trial to determine whether administration of prophylactic antibiotics is necessary during routine laparoscopic cholecystectomy in low-risk patients.\n Two hundred fifty patients without evidence of acute inflammation, common duct stones, or other indications for antibiotics were randomized to receive three perioperative doses of cefazolin or no prophylaxis and followed up for complications up to 30 days postoperatively. The primary end point was the occurrence of a major infectious complication, defined as that causing a systemic response, delaying discharge, or leading to readmission. Minor infectious problems were also noted, defined as those causing local symptoms only.\n One hundred twenty-eight patients were randomized to receive prophylactic antibiotics (PA group), 122 to receive none (NONE group; two patients in this group were actually given preoperative antibiotics). Only one major complication occurred (in a patient in the NONE group), an abscess in the presence of a bile leak, despite the administration of antibiotics when the leak was discovered several days before infectious problems arose. There were four minor problems: two lower urinary tract infections and one superficial wound infection in a NONE patient and one urinary tract infection in a PA patient (not significant); all were easily managed. The prophylactic antibiotics did not sterilize the bile, and infectious complications were not associated with weight, inflammation found at the time of operation, reported stone or bile spill-age, or conversion to open operation.\n Prophylactic antibiotics are not necessary for elective laparoscopic cholecystectomy in low-risk patients.", "Septic complications are rare following laparoscopic cholecystectomy if prophylactic antibiotics are given, as demonstrated in previous studies. Antibiotic treatment may be unnecessary and, therefore, undesirable, so we compared two forms of prophylaxis: a cephalosporin antibiotic and bag extraction of the dissected gallbladder. A total of 76 patients undergoing laparoscopic cholecystectomy were randomised to either receive an antibiotic or to have their gallbladder removed from the abdomen in a plastic bag. Complicated cases were excluded. There was a total of 6 wound infections (7.9%), 3 in each of the study groups. All these were associated with skin commensals. There were no other septic complications. Bacteriological studies grouped the organisms isolated from the bile and the wound as potential pathogens and likely commensals. A total of 10 potential pathogens were isolated, 9 of which were found in the group receiving antibiotics. We conclude that septic sequelae of uncomplicated laparoscopic cholecystectomy are uncommon, but clearly not entirely prevented by antibiotic or mechanical prophylaxis. Prophylactic antibiotics may not be required in uncomplicated laparoscopic cholecystectomy. Further study is warranted.", "Prophylactic antibiotic treatment in elective laparoscopic cholecystectomy does not lower the already low infection rate associated with this procedure.\n Prospective double-blind randomized trial at a community-based training hospital.\n Four hundred fifty patients undergoing elective laparoscopic cholecystectomy were randomized into 1 of 3 treatment arms: (1) preoperative cefotetan disodium, 1g intravenously; (2) preoperative cefazolin, 1g intravenously; and (3) intravenous placebo. There were no demographic differences between groups in age, smoking history, American Society of Anesthesiologists score, infection risk class, time of antibiotic administration prior to surgery, and type of skin preparation.\n Laparoscopic cholecystectomy was attempted in all cases; however, 10 patients required conversion to an open cholecystectomy and they were included in the statistical analysis. Preoperatively, all patients were randomized in a blinded manner and received cefotetan, cefazolin, or placebo intravenously.\n There were 10 postoperative infections. In the cefotetan group, there were 3 cases of superficial surgical site infections. In the cefazolin group, there were 2 superficial surgical site infections-1 pneumonia and 1 rhinosinusitis. In the placebo group, there were 2 superficial surgical site infections and 1 urinary tract infection. The overall infection rate in this series was 2.4%. Follow-up was performed at routine postoperative visits and by telephone contact. Data were evaluated using the chi2 test and analysis of variance with Duncan post hoc test (P<.05).\n Based on our data, use of prophylactic antibiotics does not decrease the rate of wound infections in elective laparoscopic cholecystectomy.", "At present the use of prophylactic antibiotics in elective laparoscopic cholecystectomy is controversial. This prospective study was carried out to define the role of prophylactic antibiotics in elective laparoscopic cholecystectomy to prevent postoperative infection. Ninety three patients were randomly placed in two groups. Group A comprised of 40 while group B consisted of 53 patients. Patients in Group A received 1.5 grams of second generation cephalosporin (cefuroxime sodium) diluted in 100ml of normal saline, at the time of induction of anesthesia. Group B patients received an equal volume of normal saline only. A sample of gall bladder bile was collected by direct gall bladder puncture intra-operatively for aerobic and anaerobic culture. Age, sex, weight of the patient, American Society of Anesthesiologists classification grade, presence of diabetes mellitus, episodes of colic 30 days preceding surgery, intra-operative gall bladder rupture, stone and / or bile spillage, results of bile culture, gall bladder histology, length of hospital stay, and number of septic complications were recorded and analyzed. In group A, one patient (2.5%) had post operative wound infection and in group B, two patients (3.8%) had post operative infection which was statistically similar (p>0.1). There was no difference between the two groups in terms of demographic, intra operative and post operative denominators. Therefore the study concluded that prophylactic antibiotics did not have a significant role to play in prevention of postoperative wound infection in elective laparoscopic cholecystectomy.", "Elective laparoscopic cholecystectomy (LC) has a low risk for infective complications, but many surgeons still use prophylactic antibiotics. The use of prophylactic antibiotics for LC is inconsistent and varies widely among surgeons.\n We performed a prospective double-blind randomized study of prophylactic antibiotics in elective LC. Antibiotics were was given first before the operation and then again 24 h afterward. Group A ( n = 49) received 2 g of cefotaxime; group B ( n = 43) received 10 ml of isotonic sodium chloride solution. A sample of bile was withdrawn by direct gallbladder puncture for anaerobic and aerobic cultures. Age, sex, weight, duration of surgery (DOS), presence of diabetes mellitus, American Society of Anesthesiologists (ASA) classification, gallbladder rupture, bile and/or stone spillage, gallbladder histological findings, findings from bile cultures positive for bacteria, episodes of colic within 30 days before surgery, length of stay (LOS), and number of septic complications were recorded for both groups.\n There was no differences between the two groups in terms of sex, weight, DOS, ASA score, gallbladder rupture, bile and/or stone spillage, gallbladder histological findings, findings from bile cultures positive for bacteria, or LOS. One infection occurred in the antibiotic prophylaxis group (2.04%); in the patients not receiving antibiotics, there was one other infection (2.32%). There was no statistical difference between the two groups in infective complications.\n In patients undergoing elective LC, antibiotic prophylaxis is justified only in high-risk patients. In all other patients, antibiotic prophylaxis does not seem to affect the incidence of postoperative infective complications. In low-risk patients, eliminating the unnecessary use of prophylactic antibiotics would result in a cost reduction; moreover, it would lower the risk of adverse reaction and reduce microbial resistance.", "The aim of this clinical trial was to determine whether prophylactic antibiotics could prevent surgical site infection (SSI) after laparoscopic cholecystectomy and to identify any risk factors for infection.\n The study included 100 patients undergoing laparoscopic cholecystectomy. They were randomized to receive either a single dose of ceftriaxone (Group A; n = 50) or physiologic saline as placebo (Group B; n = 50) after the induction of anesthesia. Patient demographics and clinical and surgical outcomes were recorded.\n The incidence of SSI was similar in the two groups: 2 patients in group A and 4 patients in group B (chi(2) = 0.71; p = 0.40). None of the factors studied was associated with surgical site infection statistically, as shown by binary logistic regression analysis.\n A single dose of prophylactic antibiotic failed to decrease the likelihood of SSI after laparoscopic cholecystectomy." ]

[ "7112797", "3496470", "6244414", "9580774", "8356980", "22019031", "7556234", "8165073" ]

[ "Nitrofurantoin macrocrystals prevent bacteriuria in intermittent self-catheterization.", "Suppression and treatment of urinary tract infection in patients with an intermittently catheterized neurogenic bladder.", "Prophylaxis of bacteriuria during intermittent catheterization of the acute neurogenic bladder.", "Nitrofurantoin prophylaxis for bacteriuria and urinary tract infection in children with neurogenic bladder on intermittent catheterization.", "Prophylaxis of urinary tract infection in persons with recent spinal cord injury: a prospective, randomized, double-blind, placebo-controlled study of trimethoprim-sulfamethoxazole.", "Antibiotic prophylaxis for urinary tract infections in children with spina bifida on intermittent catheterization.", "Use of norfloxacin for prevention of symptomatic urinary tract infection in chronically catheterized patients.", "A short-term study of nitrofurantoin prophylaxis in children managed with clean intermittent catheterization." ]

[ "nan", "We evaluated the optimal means of prevention and treatment of urinary tract infections in 46 patients with an intermittently catheterized neurogenic bladder. Suppression with nightly 160 mg. trimethoprim and 800 mg. sulfamethoxazole compared to placebo showed no difference in the rate of symptomatic or total urinary tract infections. Symptomatic urinary tract infections occurred at the same rate whether routine asymptomatic infections were treated or not. Three-day antibiotic treatment of urinary tract infections showed no decrease in the frequency of symptomatic or total urinary tract infections compared to 10-day therapy. The frequency of post-treatment urinary tract infection persistence, relapse and cure was identical in both groups. Suppressive antibiotics, treatment of asymptomatic urinary tract infections and full course antibiotic therapy offered no advantage over placebo, treatment of symptomatic urinary tract infection only and short course therapy in the management of urinary tract infection in patients with an intermittently catheterized neurogenic bladder.", "A randomized prospective study of bacteriuria control during early intermittent bladder catheterization was performed on a spinal cord injury service. The 64 male subjects underwent 16,620 catheterizations and had 83 significant episodes of infection. The infection rates among various groups were compared: 1) control patients, 2) patients treated with intravesical neomycin/polymyxin-B, 3) patients given low dose daily macrocrystals of nitrofurantoin and 4) patients given intravesical treatment and oral nitrofurantoin. There was significant reduction in infection rates when oral and intravesical antibiotics were used.", "To determine the effect of nitrofurantoin prophylaxis on rates of bacteriuria and symptomatic urinary tract infection in children with chronic neurogenic bladder receiving clean intermittent catheterization.\n Double-blind, placebo-controlled, crossover trial of 15 children receiving nitrofurantoin or placebo for 11 months (5 months receiving one drug, then 1 month of washout followed by 5 months of the alternate drug). Weekly home visits were made. During each visit a sample of bladder urine was obtained by intermittent catheterization, signs and symptoms of urinary tract infection were recorded, and all medications were recorded as well as a capsule count of the study drug.\n During nitrofurantoin the frequency of bacteriuria remained high. Cultures of 74% (203 of 274) of the 274 samples on placebo were positive for a pathogen (> or = 10(4) colony-forming units per milliliter) compared with 65% (165 of 252) of the 252 samples on nitrofurantoin. The bacterial species responsible for bacteriuria, however, were altered; Escherichia coli, the most common pathogen isolated during placebo, was replaced by resistant Klebsiella spp. and Pseudomonas spp. during nitrofurantoin. The carriage of these resistant organisms tripled during nitrofurantoin. Symptomatic infection dropped in half on nitrofurantoin, but this decline was due solely to infections caused by E. coli. Despite an increased frequency of resistant organisms on nitrofurantoin prophylaxis, an increase in urinary tract infections caused by these resistant organisms did not occur.\n Routine use of nitrofurantoin prophylaxis in an attempt to eradicate bacteriuria in patients with chronic neurogenic bladder is not effective.", "To determine the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for prophylaxis of urinary tract infection in persons with recent spinal cord injury, during the first 4 months of intermittent catheterization.\n One hundred twenty-nine adults (112 men, 17 women) with recent acute spinal cord injury participated in a randomized, double-blind, placebo-controlled trial, and were studied for up to 16 weeks. Low-dose TMP-SMX (TMP 40 mg, SMX 200 mg) or placebo was given once daily. Clinical observations, urine cultures, and cultures of rectal and urethral swabs were made weekly. Subjects who developed breakthrough bacteriuria received conventional antimicrobial therapy and prophylaxis was continued.\n Sixty-six TMP-SMX recipients (57 men, 9 women) and 60 placebo recipients (52 men, 8 women) are evaluable for efficacy. Among male subjects, bacteriuria was present during 50% or more of study weeks in 30% of TMP-SMX recipients and in 56% of placebo recipients (p = 0.003). The interval to the onset of bacteriuria was prolonged in TMP-SMX recipients (p < 0.0001). TMP-SMX recipients without bacteriuria in any given week had a lower probability of having bacteriuria the subsequent week (0.26) than did placebo recipients (0.49) (p < 0.0001). At least 1 episode of definite symptomatic bacteriuria (bacteriuria and fever and at least 1 classical manifestation of urinary infection) occurred in 4 of 57 TMP-SMX-treated men and in 18 of 52 placebo-treated men (p < 0.0003). We observed similar trends in women, but differences did not reach statistical significance, perhaps because the number of females was small. Adverse events suspected to be due to medications were frequent in this population of patients with recent severe injuries and led to discontinuation of the study in 10% of the TMP-SMX group and 8% of the placebo group. Adverse events included neutropenia (TMP-SMX: two; placebo: three), pseudomembranous colitis (TMP-SMX: one), severe skin rash (TMP-SMX: two; placebo: one), and drug fever (TMP-SMX: one). The proportion of all episodes of bacteriuria that were due to TMP-SMX-resistant organisms was unexpectedly high in the placebo group (51%), and increased progressively according to year of enrollment in the study. By Year 3, all subjects in the placebo group had at least one episode of TMP-SMX-resistant bacteriuria. Gram-negative enteric bacilli resistant to TMP-SMX were recovered from rectal swabs (TMP-SMX 49%, placebo 42%) and urethral swabs (TMP-SMX 33%, placebo 26%) in similar proportions of subjects in the two study groups.\n Prophylaxis with TMP-SMX significantly reduces bacteriuria and symptomatic urinary tract infection in persons with recent acute spinal cord injury during bladder retraining using intermittent catheterization. However, adverse reactions attributable to TMP-SMX are common in this population. Colonization and breakthrough bacteriuria with TMP-SMX-resistant organisms are frequent and may seriously limit the usefulness of this strategy, particularly in an institutional setting.", "Antibiotic prophylaxis (low dose chemoprophylaxis) has been prescribed since the introduction of clean intermittent catheterization in children with spina bifida. We hypothesized that stopping low dose chemoprophylaxis does not increase the number of urinary tract infections in these patients.\n A total of 176 patients with spina bifida participated in a randomized controlled trial (ISRCTN trial number 56278131) of either continuation or discontinuation of low dose chemoprophylaxis. During the 18-month study period biweekly urine samples were evaluated for leukocyturia and bacteriuria with dipsticks and cultures. Asymptomatic significant bacteriuria (positive culture results without clinical symptoms) and urinary tract infections (significant bacteriuria with clinical symptoms and leukocyturia) were analyzed.\n Discontinuation of low dose chemoprophylaxis resulted in higher rates of asymptomatic significant bacteriuria (incidence rate ratio 1.23, 95% CI 1.08-1.40, p = 0.002) and urinary tract infection (IRR 1.44, 95% CI 1.13-1.83, p = 0.003). For urinary tract infection the number needed to harm was 2.2, that is if 2 patients discontinued low dose chemoprophylaxis for a year, 1 extra urinary tract infection would result. Febrile urinary tract infection occurred once in every 30 patient-years and slightly more often in the discontinuation group (relative risk 2.0, 95% CI 0.38-10.6, p = 0.4). Of 88 patients allocated to discontinuation of low dose chemoprophylaxis 38 (43%) switched back to chemoprophylaxis. The urinary tract infection rate was nonsignificantly higher in the presence of vesicoureteral reflux. Male gender and a low pre-study rate of urinary tract infection predicted successful discontinuation.\n Patients with spina bifida on clean intermittent catheterization and antibiotic prophylaxis for urinary tract infections can safely discontinue this prophylaxis, in particular males, patients with low urinary tract infection rates and patients without vesicoureteral reflux.\n Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.", "Thirty-four elderly inpatients with long-term urethral catheters were randomly assigned to receive either norfloxacin (200 mg/day) or placebo in a double-blind study with cross-over after three months. Twenty-three patients completed the entire study. Norfloxacin treatment was associated with a persistent decrease in gram-negative isolates (p < 0.005) and the acquisition of gram-positive norfloxacin-resistant flora. It also resulted in a highly statistically significant reduction of symptomatic urinary tract infections (1 vs. 12, p < 0.02), a decrease in catheter-associated local complications, obstructions and leakage (p < 0.05) and an improvement in the patients' general condition (p < 0.001). In conclusion, within the conditions of the present study, long-term suppression of gram-negative bacteriuria by norfloxacin reduced the incidence of catheter-related urinary tract infection and associated morbidity.", "Because there is no evidence for the effectiveness of antibiotic prophylaxis in children with neurogenic bladder, the value of once-daily nitrofurantoin macrocrystals was assessed in a selected population with neurogenic bladder due to meningomyelocele. METHODS AND TRIAL POPULATION: Children with significant urinary tract abnormalities other than neurogenic bladder were excluded. A urinary tract \"infection\" was defined as > or = 10(8) colony forming units of bacteria/L of urine together with pyuria of > or = 50 x 10(6) leukocytes/L, and/or symptoms consistent with an urinary tract infection. Fifty-six children participated in a 24-week double-blinded, placebo-controlled cross-over study. The infection status was assessed at two weekly intervals or if relevant clinical manifestations occurred.\n For the whole trial the average percentage of \"infections\" per urine sample for each patient was reduced from 39% on placebo to 19% on single daily dose prophylaxis (P < .0003). For the first 12 weeks of the trial corresponding figures were 45% on placebo and 22% on prophylaxis (P < .0018). There was evidence for a marked carryover protective effect of nitrofurantoin into the placebo arm of the trial.\n Nitrofurantoin is an effective prophylactic agent during a 3-month period. Long-term studies are needed to confirm the reasonable expectation of a beneficial effect on urinary tract damage." ]

[ "8708839", "3389899" ]

[ "Comparison of two percutaneous intravenous \"midline\" catheters in cystic fibrosis.", "Silastic catheters for antibiotics in cystic fibrosis." ]

[ "Administration of intravenous antibiotics in cystic fibrosis has been facilitated by the use of midline catheters; percutaneous lines inserted through a peripheral vein and advanced into a large but noncentral vein. In a randomized study, a 23-gauge silastic catheter (Vygon EC, Cirencester, United Kingdom) was compared with the Hydrocath (Viggo-Spectromed, Swindon, United Kingdom), a 22-gauge hydrophillic coated polyurethane catheter inserted using the Seldinger technique. Fifty eight courses of intravenous antibiotics were given, 28 through the Hydrocath (median age 11 years, range 1.5-17.5 years) and 30 through the silastic catheter, (median age 11 years, range 0.5-17.5). Mean line survival was equal. The Hydrocath took longer to insert and was associated with more pain on insertion. However, administration of antibiotics was easier through the Hydrocath and overall satisfaction was higher in those who had the Hydrocath. Both catheters performed well, but administration of antibiotics was easier through the Hydrocath.", "A randomised comparison of percutaneous Silastic catheters and conventional intravenous cannulae for giving intravenous antibiotics in patients with cystic fibrosis showed that Silastic catheters were favoured by the patient, lasted longer, and had fewer complications." ]

[ "15135594", "8418401" ]

[ "Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.", "Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. The Veterans Affairs Cooperative Study Group." ]

[ "Among patients with substantial carotid artery narrowing but no recent neurological symptom (stroke or transient ischaemia), the balance of surgical risks and long-term benefits from carotid endarterectomy (CEA) was unclear.\n During 1993-2003, 3120 asymptomatic patients with substantial carotid narrowing were randomised equally between immediate CEA (half got CEA by 1 month, 88% by 1 year) and indefinite deferral of any CEA (only 4% per year got CEA) and were followed for up to 5 years (mean 3.4 years). Kaplan-Meier analyses of 5-year risks are by allocated treatment.\n The risk of stroke or death within 30 days of CEA was 3.1% (95% CI 2.3-4.1). Comparing all patients allocated immediate CEA versus all allocated deferral, but excluding such perioperative events, the 5-year stroke risks were 3.8% versus 11% (gain 7.2% [95% CI 5.0-9.4], p<0.0001). This gain chiefly involved carotid territory ischaemic strokes (2.7% vs 9.5%; gain 6.8% [4.8-8.8], p<0.0001), of which half were disabling or fatal (1.6% vs 5.3%; gain 3.7% [2.1-5.2], p<0.0001), as were half the perioperative strokes. Combining the perioperative events and the non-perioperative strokes, net 5-year risks were 6.4% versus 11.8% for all strokes (net gain 5.4% [3.0-7.8], p<0.0001), 3.5% versus 6.1% for fatal or disabling strokes (net gain 2.5% [0.8-4.3], p=0.004), and 2.1% versus 4.2% just for fatal strokes (net gain 2.1% [0.6-3.6], p=0.006). Subgroup-specific analyses found no significant heterogeneity in the perioperative hazards or (apart from the importance of cholesterol) in the long-term postoperative benefits. These benefits were separately significant for males and females; for those with about 70%, 80%, and 90% carotid artery narrowing on ultrasound; and for those younger than 65 and 65-74 years of age (though not for older patients, half of whom die within 5 years from unrelated causes). Full compliance with allocation to immediate CEA or deferral would, in expectation, have produced slightly bigger differences in the numbers operated on, and hence in the net 5-year benefits. The 10-year benefits are not yet known.\n In asymptomatic patients younger than 75 years of age with carotid diameter reduction about 70% or more on ultrasound (many of whom were on aspirin, antihypertensive, and, in recent years, statin therapy), immediate CEA halved the net 5-year stroke risk from about 12% to about 6% (including the 3% perioperative hazard). Half this 5-year benefit involved disabling or fatal strokes. But, outside trials, inappropriate selection of patients or poor surgery could obviate such benefits.", "The efficacy of carotid endarterectomy in patients with asymptomatic carotid stenosis has not been confirmed in randomized clinical trials, despite the widespread use of operative intervention in such patients.\n We conducted a multicenter clinical trial at 11 Veterans Affairs medical centers to determine the effect of carotid endarterectomy on the combined incidence of transient ischemic attack, transient monocular blindness, and stroke. We studied 444 men with asymptomatic carotid stenosis shown arteriographically to reduce the diameter of the arterial lumen by 50 percent or more. The patients were randomly assigned to optimal medical treatment including antiplatelet medication (aspirin) plus carotid endarterectomy (the surgical group; 211 patients) or optimal medical treatment alone (the medical group; 233 patients). All the patients at each center were followed independently by a vascular surgeon and a neurologist for a mean of 47.9 months.\n The combined incidence of ipsilateral neurologic events was 8.0 percent in the surgical group and 20.6 percent in the medical group (P < 0.001), giving a relative risk (for the surgical group vs. the medical group) of 0.38 (95 percent confidence interval, 0.22 to 0.67). The incidence of ipsilateral stroke alone was 4.7 percent in the surgical group and 9.4 percent in the medical group. An analysis of stroke and death combined within the first 30 postoperative days showed no significant differences. Nor were there significant differences between groups in an analysis of all strokes and deaths (surgical, 41.2 percent; medical, 44.2 percent; relative risk, 0.92; 95 percent confidence interval, 0.69 to 1.22). Overall mortality, including postoperative deaths, was primarily due to coronary atherosclerosis.\n Carotid endarterectomy reduced the overall incidence of ipsilateral neurologic events in a selected group of male patients with asymptomatic carotid stenosis. We did not find a significant influence of carotid endarterectomy on the combined incidence of stroke and death, but because of the size of our sample, a modest effect could not be excluded." ]

[ "15474542", "17010026", "16818549", "15671970", "15288567", "15811544", "10868755", "16210193", "18571571", "18054596", "11585482", "17366334", "15530926", "18606272", "18786425", "16546622", "11585481", "17907021", "16294597", "8703271" ]

[ "Effects of the California graduated driver licensing program.", "Graduated drivers license programs and rural teenage motor vehicle fatalities.", "Graduated driver licensing programs and fatal crashes of 16-year-old drivers: a national evaluation.", "Graduated driver licensing in Utah: is it effective?", "Michigan's graduated driver licensing program: evaluation of the first four years.", "Graduated driver licensing and teen traffic fatalities.", "Effect of Florida's graduated licensing program on the crash rate of teenage drivers.", "Specific and long-term effects of Nova Scotia's graduated licensing program.", "Does the Maryland graduated driver licensing law affect both 16-year-old drivers and those who share the road with them?", "California's graduated driver license law: Effect on teenage drivers' deaths through 2005.", "Graduated driver licensing in Michigan: early impact on motor vehicle crashes among 16-year-old drivers.", "The effects of graduated driver licensing on hospitalization rates and charges for 16-and 17-year-olds in North Carolina.", "Evaluation of California's graduated driver licensing program.", "Evaluation of Iowa's graduated driver's licensing program.", "The Iowa Graduated Driver Licensing program: effectiveness in reducing crashes of teenage drivers.", "Impact of Georgia's Teenage and Adult Driver Responsibility Act.", "Initial effects of graduated driver licensing on 16-year-old driver crashes in North Carolina.", "Effect of a graduated licensing system on motor vehicle crashes and associated injuries involving drivers less than 18 years-of-age.", "Graduated driver licensing in Wisconsin: does it create safer drivers?", "An evaluation of the New Zealand graduated driver licensing system." ]

[ "On July 1, 1998, in an effort to ameliorate the problem of high teenage driver crash rates, California implemented a graduated driver licensing system (GDLS).\n Data on injury crashes of 16- and 17-year-old drivers from a pre-GDLS year were compared with data from two post-GDLS years. Per-capita crash rate ratios were adjusted for changes in crash rates of 25- to 34-year-old drivers, who were unaffected by the GDLS. Prevented numbers and 95% confidence intervals were estimated.\n Fatal or severe injury crash rates were significantly lower during each of the two post-GDLS years (adjusted rate ratios (RR)=0.72 and 0.83, for 2000 vs. 1997 and 2001 vs. 1997, respectively). Significant rate reductions were observed for all crash types, particularly for struck object (RR=0.71 and 0.80, for 2000 vs. 1997 and 2001 vs. 1997, respectively) and non-collision (RR=0.63 and 0.72, for 2000 vs. 1997 and 2001 vs. 1997, respectively). Minor injury crash rates were also lower during post-GDLS years (RR=0.87 and 0.90, for 2000 vs. 1997 and 2001 vs. 1997, respectively). Percent reductions were notably larger during the hours of the late night driving restriction (midnight-5 a.m.) (RR=0.79 and 0.87, for 2000 vs. 1997 and 2001 vs. 1997, respectively).\n The implementation of the California GDLS was followed by large reductions in the rate of injury-producing motor-vehicle crashes.\n This evaluation supports previous evidence that GDLS is an effective countermeasure to adolescent motor-vehicle crashes and their associated injuries. States with a traditional licensing system may prevent adolescent driver crashes by adopting a GDLS. Future studies should examine factors that influence teenager compliance with GDLS provisions and identify approaches to improving compliance.", "Graduated drivers license (GDL) programs have been shown to reduce motor vehicle fatalities among 15- to 17-year-olds. However, the 20 most rural states have been the least likely to enact more stringent GDL policies.\n Estimate the relationship of GDL programs and the number of traffic fatalities among 15- to 17-year-olds on rural interstate and noninterstate roadways.\n Analysis of 1992-2002 Fatality Analysis Reporting System data and a compendium of state laws using a conditional negative binominal regression model with full fixed effects to control for unobservable differences across states and years.\n Overall, GDL programs were associated with a 7.8% reduction in rural traffic fatalities among 15- to 17-year-olds. Virtually all of this reduction took place on noninterstate roadways. The most stringent GDL programs were associated with a nearly 22% reduction in this age group and were the only programs associated with reductions in fatalities among 15- to 17-year-old drivers.\n Rural states should consider enacting stringent GDL programs. Had the 19 of the 20 most rural states without such programs all adopted the most stringent GDL programs in 2002, the analysis suggests that 64 traffic deaths among 15- to 17-years-olds could have been prevented.", "Implementation of graduated driver licensing programs is associated with reductions in crash rates of young drivers, but graduated driver licensing programs vary in their components. The impact of programs with different components is unknown.\n The purpose of this work was to determine which graduated driver licensing programs are associated with the greatest reductions in fatal motor vehicle crashes involving 16-year-old drivers.\n We conducted a retrospective study of all 16-year-old drivers involved in fatal crashes in the United States from 1994 through 2004 using data from the Fatality Analysis Reporting System and the US Census Bureau. We measured incidence rate ratios of fatal motor vehicle crashes involving 16-year-old drivers according to graduated driver licensing programs, adjusted for state and year.\n Compared with state quarters with no graduated driver licensing program components, reductions of 16% to 21% in fatal crash involvement rates of 16-year-old drivers occurred with programs that included > or = 3-month mandatory waiting period, nighttime driving restriction, and either > or = 30 hours of supervised driving or passenger restriction. Reductions of 18% to 21% occurred in state quarters with programs that included > or = 5 of the 7 components examined. Drivers aged 20 to 24 or 25 to 29 years did not experience significant reductions.\n Comprehensive graduated driver licensing programs are associated with reductions of approximately 20% in 16-year-old drivers' fatal crash involvement rates. The greatest benefit seems to be associated with programs that include age requirements and > or = 3 months of waiting before the intermediate stage, nighttime driving restriction, and either > or = 30 hours of supervised driving or passenger restriction.", "We seek to examine the effectiveness of the graduated driver licensing system in Utah by determining whether crash rates of 16-year-old drivers decreased after graduated driver licensing implementation.\n We studied 16-year-old-driver crashes using statewide motor vehicle crash data probabilistically linked to emergency department (ED), hospital inpatient, and driver licensure data for 1996 to 2001. Outcomes examined included overall crash rates, nighttime crashes, crash severity indicators (eg, noninjury crash, injury crash, ED crash, inpatient crash, fatal crash), seat belt usage, licensure status, and citations. Rate ratios (RR), chi 2 tests, and interventional time series analyses were used to assess changes before and after graduated driver licensing implementation.\n There were 27,304 16-year-old-driver crashes during the study period. The overall crash rate per 1,000 licensed 16-year-old drivers decreased by 5% (RR 0.95; 95% confidence interval [CI] 0.92 to 0.97), and a time-series analysis showed a reduction of 0.8 (SD 0.39) crashes per month per 1,000 licensed drivers after graduated driver licensing implementation (1996 to 1999 versus 1999 to 2001). The nighttime crash rate did not change (RR 0.91; 95% CI 0.78 to 1.04), and there was no association between crash severity and graduated driver licensing implementation ( P =.096). Reported seat belt usage increased by 6.3%, and few graduated driver licensing citations were issued by law enforcement.\n The results suggest that graduated driver licensing may have contributed to a reduction in young driver crashes, but the effects were minimal compared with those shown in many other graduated driver licensing evaluations.", "To evaluate the four-year outcome of Michigan's graduated driver licensing (GDL) program, motor-vehicle crash data for 16-year-old drivers in 1996 (pre-GDL), and 1998-2001 (post-GDL) were analyzed.\n Relative risks and 95% confidence intervals for several crash types were computed, and pre-post-GDL population-based crash rates were compared. Reductions in crash risks among 16-year-olds previously found in 1998 and 1999 were generally maintained in 2000 and 2001.\n Reductions in crash risk among 16-year-olds from 1996 to 2001 were 29% for all, 44% for fatal, 38% each for nonfatal-injury and fatal-plus-nonfatal-injury, 32% for day, 31% for evening, 59% for night, 32% for single-vehicle, and 28% for multi-vehicle crashes. Even after adjusting for more general population-wide changes among drivers 25 years and older that might have contributed to changes in 16-year-old crash risk, reductions remained impressive (19% for all crashes in 2001).\n As one approach to reducing teenage motor-vehicle morbidity and mortality, GDL remains promising.", "Over the last 8 years, nearly every state has introduced graduated driver licensing (GDL) for teens. These new licensing procedures require teen drivers to advance through distinct stages where they are subject to a variety of restrictions (e.g., adult supervision, daytime driving, passenger limits). In this study, we present evidence on whether these restrictions have been effective in reducing traffic fatalities among teens. These evaluations are based on state-by-year panel data from 1992 to 2002. We assess the reliability of our basic inferences in several ways including an examination of contemporaneous data for older cohorts who were not directly affected by these policies. Our results indicate that GDL regulations reduced traffic fatalities among 15-17-year-olds by at least 5.6%. We also find that the life-saving benefits of these regulations were plausibly related to their restrictiveness. And we find no evidence that these benefits were attenuated by an increase in fatality risks during the full-licensure period available to older teens.", "On 1 July 1996, Florida instituted a graduated licensing program for drivers younger than age 18. For the first 3 months, holders of learner's licenses are not allowed to drive at all between 19:00 and 06:00 h; thereafter, they may drive until 22:00 h. Learner's licenses must be held for 6 months prior to eligibility for the intermediate license. Sixteen-year-old intermediate license holders are not permitted to drive unsupervised from 23:00 to 06:00 h, 17 year-olds from 01:00 to 06:00 h. All drivers younger than 18 have strict limits on the number of traffic violations they can accumulate and, effective 1 January 1997, all drivers younger than 21 are subject to a zero tolerance law for drinking and driving. Florida crash data for 1995-1997 were obtained and compared with similar data from Alabama, a state that borders Florida but does not have graduated licensing. For 15, 16, and 17 year-olds combined, there was a 9% reduction in the fatal and injury crash involvement rate in Florida during 1997, the first full year of graduated licensing, compared with 1995. On a percentage basis, crashes declined most among 15 year-olds, followed by 16 year-olds and then 17 year-olds. Reductions were not seen among Alabama teenagers nor among 18 year-olds in Florida.", "A graduated licensing (GL) program was introduced in Nova Scotia, Canada, in October 1994. Previous research has shown that it reduced collisions in the short term. The present study examined the relative contribution of each stage of the program (i.e., learner and intermediate levels) and the program's impact after beginning drivers graduated to full licensure. The research focused on teenage beginning drivers (age 16-17), but the effects on older beginners also was examined. Per-driver crash rates of two groups of novices selected from driver records in Nova Scotia were compared. One group (pre-GL) received their learner's permits during the 2 years before the program was implemented, and the second group (GL) received their learner's permits during the 2 years after implementation. The findings clearly establish that most of the collision reduction in Nova Scotia's program occurred during the first year of the program, particularly during the first 6 months when the majority of novices were driving under supervision. The collision rate for 16 to 17-year-old GL novices was 50% lower than the rate for pre-GL novices during the 6 months after they received their learner's permits, and about 10% lower during their first 2 years of licensure when unsupervised driving from midnight to 5 A.M. was prohibited. Much of this improvement for 16 to 17-year-olds occurred during restricted night hours. Collision rates also were lower during nonrestricted hours in the initial 6 months of licensure. The 3-month \"time discount\" for driver education provided no safety benefit, and GL novices with driver education had collision rates that were not lower than pre-GL novices. There was no long-term effect found for the program after 16 to 17-year-olds graduated to full licensure. For older beginning drivers, crash rates during the first year after obtaining a learner's permit showed a 31% reduction. This effect diminished rapidly. There was only a 2% reduction during the first year of licensure, and crash rates increased during the following 2 years. Overall the data indicate substantial benefits of graduated licensing for 16 to 17-year-old beginners, but no benefits beyond the learner stage for older beginners.", "To assess effects of the 1999 Maryland graduated driver licensing (GDL) law on both 16-year-old drivers and other road users.\n Calculation and comparison of crash involvement rates and non-fatal injury rates pre-GDL (1996-1998) and post-GDL (2001-2003) by type of road user, per population, and per licensed driver, with adjustment for trends among 30-59-year-old drivers.\n Post-GDL, prevalence of licensure decreased 24% among 16-year-olds, and rates of 16-year-old drivers involved in crashes significantly decreased per 16-year-old population (corrected rate ratio (RRc) 0.82; 95% CI (0.71, 0.96)). A significant decrease also was observed for non-fatal injuries per 16-year-old population among 16-year-old drivers involved in crashes (RRc 0.63; 95% CI (0.41, 0.98)). Similarly, decreases, albeit not statistically significant, were observed among their passengers and other vehicle occupants. Per 16-year-old licensed driver, a slight non-significant increase was observed in crash involvement rates; non-fatal injury rates per 16-year-old licensed driver suggest decreased risk (non-significant) among 16-year-old drivers, their passengers, and other vehicle occupants.\n Maryland's GDL delayed licensure and reduced crashes and non-fatal injuries among 16-year-old drivers per population. Trends in injuries among other road users involved in crashes with 16-year-old drivers were suggestive of a benefit from GDL, although observed decreases were not significant. Per licensed driver, findings were not significant, but suggested little change in crash involvement and decreased non-fatal injuries. Because one-third fewer 16-year-olds were licensed post-GDL, these results may suggest a selection effect in licensure.\n Because Maryland had nighttime restrictions for new drivers before 1999, this study suggests other components of GDL are beneficial for drivers and possibly for other road users. States with weak GDL laws should strongly consider revising them.", "While many researchers believe Graduated Driver Licensing (GDL) laws save lives by imposing restrictions and delayed licensure on drivers under age 18, longer term effects on older teenagers have not been studied.\n The effects of California's strict GDL law on deaths of drivers ages 16-19 were analyzed for 1995-2005 using Incidence Rate Ratios (IRR) and Auto-Regressive Integrated Moving Average (ARIMA) time series analysis of Fatality Analysis Reporting System mortality data.\n The two methods yielded similar results. IRR analysis found California 16-year-old drivers subject to the GDL experienced a 15% fatality decline (95% CI, 0.70-0.99), while 18 year-old drivers experienced a 15% increase (95% CI, 1.02-1.27). ARIMA analysis found 16 year-old drivers experienced a near-significant 20% fatality decline (p=0.07), while 18 year-olds experienced a 24% increase (p=0.01). Unlicensed teenage drivers and older teen drivers driving alone and transporting teenage passengers suffered significant fatality increases.\n California's GDL may negatively affect older teenagers and other driver subpopulations and merits reevaluation.", "Graduated driver licensing (GDL) programs are being adopted in many states to address the high rate of motor vehicle fatalities among teens by requiring teenaged drivers to gain experience and maturity under conditions of relatively low crash risk before gaining full driving privileges.\n To evaluate the early impact of Michigan's GDL program on traffic crashes among 16-year-old drivers.\n Analysis of Michigan motor vehicle crash data from 1996 (before GDL program implementation) vs 1998 and 1999 (after GDL program implementation) for 16-year-olds, adjusting for trends among persons 25 years or older.\n Michigan's GDL program, instituted April 1, 1997, for teens younger than 18 years entering the driver license system, includes 3 licensure levels, each with driving restrictions and requirements to progress to the next level. Requirements include extended, supervised practice in the learning level, 2-phase driver education, and night driving restrictions in the intermediate level.\n Rates in 1996 vs 1998 and 1999 for all police-reported crashes; for fatal injury, nonfatal injury, and fatal/nonfatal injury combined crashes; for day, evening, and night crashes; for single-vehicle and multivehicle crashes; and for alcohol-related crashes.\n Overall, the rate of 16-year-old drivers (per 1000 population) involved in crashes declined from 154 in 1996 to 111 in 1999 (relative risk [RR], 0.72; 95% confidence interval [CI], 0.71-0.73). After adjusting for populationwide trends, the overall crash risk for 16-year-olds was significantly reduced in 1999 from 1996 by 25% (adjusted RR, 0.75; 95% CI, 0.74-0.77). There were also significant reductions for nonfatal injury and combined fatal and nonfatal crashes; for day, evening, and night crashes; and for single-vehicle and multivehicle crashes. Fatal crashes declined from 1996 to 1999, but not significantly (RR, 0.74; 95% CI, 0.49-1.14), and alcohol-related crashes continued at a low rate (RR, 1.01; 95% CI, 0.80-1.29).\n Analysis of the first 2 full calendar years following Michigan's GDL program implementation indicates substantial crash reductions among 16-year-olds. Future research is necessary to determine if these reductions are maintained and if other jurisdictions achieve similar results.", "To mitigate the high risk of motor vehicle crashes for young beginning drivers, over 40 states and the District of Columbia have implemented graduated driver licensing (GDL) systems that gradually and systematically ease teen drivers into higher risk driving conditions. Evaluations of GDL programs using motor vehicle crash data have demonstrated marked declines in crashes. The objective of this study is to examine the association between the implementation of the North Carolina GDL program and the rate of hospitalization, as well as hospital charges, for 16-and 17-year-old drivers.\n Data were obtained from the North Carolina Hospital Discharge Database for the 26 months before and 46 months after the December 1, 1997, implementation of the GDL program. ARIMA interrupted time series analyses were used to model monthly hospitalization rates, controlling for the hospitalization rates of 25-to 54-year-old drivers. ARIMA analyses were also used to determine whether changes occurred in monthly total hospital charges.\n Among the 568 16-year-old hospitalized drivers, GDL was associated with a 36.5% decline in the hospitalization rate per population and a 31.2% decline in the total monthly driver hospitalization charges. Although a 12% reduction in the rate of hospitalizations was observed among the 615 17-year-old drivers, the analysis lacked sufficient power to be statistically reliable. No consistent change was observed in the 16-year-old driver total monthly hospital charges.\n The North Carolina GDL program was associated with a marked decline in the rate of hospitalizations and hospital charges for 16-year-old drivers. Following the implementation of GDL, over $650,000 in hospital charges have been averted each year for 16-year-old drivers. Analyses suggest these reductions were primarily the result of reduced exposure rather than an improvement in teen driving.", "California's graduated driver licensing (GDL) program was implemented to reduce the high crash risk of teenage drivers. The program enhancements made in 1998 were evaluated in this study using methods that rule out the noticeable downward trend in California teen's fatal/injury crash rates as a possible explanation for any observed crash reductions that could otherwise be mistaken for program effects.\n Monthly per capita fatal/injury crash rates for 15-to-17-year-olds and proportional representations of 16-17-year-olds' nighttime and passenger crashes were analyzed using intervention time series analysis.\n After removing trend, seasonality, and transition effects in the data, no overall reductions in fatal/injury crashes for 15-17-year-olds or 16-year-olds (separately) were found to be associated with the 1998 program enhancements, suggesting no overall exposure reduction effect of the longer instruction permit period nor increased competency associated with the higher number of required practice hours. However, the 12-month nighttime and 6-month passenger restrictions were found to be associated with annual savings of 55 and 816 fatal/injury crashes, respectively.\n Finding no overall impact of the 1998 GDL enhancements was not surprising given findings of an earlier survey suggesting that California teens and parents were largely already practicing program requirements prior to implementation and were not fully complying with the program requirements afterwards. Though the observed crash savings associated with the restrictions were of modest size, this is the first study to evidence a direct positive impact of the passenger restriction component of GDL programs. Larger reductions could be realized if the nighttime restriction started earlier and parents/law enforcement could be motivated to better enforce these restrictions.\n The findings provide support for passenger and nighttime restriction components of GDL programs.", "The effectiveness of Iowa's graduated driver's licensing (GDL) program was evaluated for a 4-year period before and after implementation in 1999. Since some changes had occurred in the crash reporting format, changes in crash rates for younger drivers were compared to those for 35-44-year-old drivers (middle-age group of drivers) who were used as a control group. After implementation of GDL, the 14-, 16- and 17-year-old age groups experienced a greater decrease in crash rate than the middle-age control group while 15-year-old experienced a smaller decrease. This suggests that the crash rate for 15-year-old drivers may actually have increased when downward trends were adjusted for. Iowa's GDL program allows holders of the instruction permit to travel unaccompanied to and from school and school-endorsed activities after obtaining a minor school license. Fifteen-year-old with minor school licenses account for up to 26.7% of 15-year-old license holders yet represent up to 74.8% of 15-year-old drivers involved in crashes (depending on the year) from 1998 to 2004. As a result, 15-year-old drivers with minor school licenses are involved in 7.2-8.9 times more crashes, are 7.7 times more likely to have one or more sanctions, and are 4.8 times more likely to receive one or more moving convictions than their peers with a regular instruction permit. This help may explain why 15-year-old drivers did not seem to benefit from implementation of the GDL program in Iowa.", "Graduated Driver Licensing (GDL) programs vary in the United States in terms of implementation and restrictions. The State of Iowa's GDL program is assessed for its effectiveness in reducing crashes among teenage drivers.\n Time series analysis was used to evaluate police documented crashes involving 16-, 17-, and 18-year-old drivers over a 10 year period, with an intervention identified at the point of GDL implementation.\n After controlling for seasonal trends and auto-correlative effects, a significant reduction in the crash rate of and 16- and 17-year-old drivers was observed due to the GDL implementation. However, there were no significant reductions in crash rates for 18-year-old drivers.\n The analyses suggest that the Iowa GDL program is effective in reducing the crash rates of 16- and 17-year-old drivers but the effects do not sustain for 18-year-old drivers.\n The results suggest that the program appears to be working, however further analysis is needed to determine what factors are preventing lasting effects for these teenage drivers.", "In 1997, the Georgia General Assembly enacted the Teenage and Adult Drivers Responsibility Act (TADRA), a comprehensive legislative package that attempted to reduce fatal crashes of teenaged drivers by introducing graduated driver's licensing, \"zero tolerance\" of underage impaired drivers, and automatic license revocation for speeding greater than 25 miles per hour over the posted limit and other dangerous driving behaviors. To determine whether TADRA reduced teen driving fatalities, we examine fatal crash rates involving various age groups before versus after the law was enacted.\n Data from the Fatal Accident Reporting System were used to calculate annualized fatal crash rates of various age groups of drivers during an 11-year interval 5 1/2 years before TADRA was enacted and 5 1/2 years afterwards. To identify potential historical effects, Georgia's experience was compared to that of Alabama, South Carolina, and Tennessee, states that did not adopt equally comprehensive legislation during the study period.\n During the preenactment period, 317 Georgia drivers aged 16 were involved in a fatal crash (57/100,000 person-years) compared to 230 in the postenactment period (36/100,000 person-years; risk ratio [RR] 0.63; 95% confidence interval 0.53 to 0.75). Speed-related fatal crashes were cut by 42%, and alcohol-related fatal crashes decreased nearly 60%, without displacing fatal crashes to older age groups. These reductions greatly exceeded those noted in 2 of 3 comparison states and the nation overall.\n TADRA markedly reduced fatal crash rates among 16-year-old Georgia drivers. Fatal crashes were not displaced to older age groups.", "Since 1997, 32 states have enacted graduated driver licensing (GDL) systems to reduce crash rates among young novice drivers.\n To determine the initial effect of the North Carolina GDL system on crashes among 16-year-old drivers.\n Comparison of population-based North Carolina motor vehicle crash rates before (1996-1997) and after (1999) 16-year-old drivers were licensed under the GDL system. To control for other factors that might have influenced crashes, changes for 16-year-old drivers were compared with those of drivers 25 to 54 years of age. Crashes per licensed driver were also examined.\n The North Carolina GDL system, enacted December 1, 1997, requires beginning drivers 15 to 17 years of age to hold level 1 licenses, allowing driving only while supervised by a designated adult for a full year; followed by level 2 licensure, allowing unsupervised driving from 5 AM to 9 PM and supervised driving at any time for at least 6 months; and, finally, level 3-a full, unrestricted license.\n Rates of motor vehicle crashes among 16-year-old drivers in 1996-1997 vs 1999, overall and by crash severity (fatal, injury, and noninjury), time (night vs day), type (single vs multiple vehicle), driver alcohol use, and driving environment (more vs less rural counties).\n Crash rates declined sharply for all levels of severity among 16-year-old drivers after the GDL program was implemented. Following GDL, 16-year-old driver crashes were substantially less likely. Comparing 1996 with 1999, fatal crashes declined 57%, from 5 to 2 per 10 000 population (rate ratio [RR], 0.43; 95% confidence interval [CI], 0.27-0.70); crashes with no or minor injuries decreased 23%, from 1068 to 826 per 10 000 (RR, 0.77; 95% CI, 0.75-0.80). Nighttime crashes were 43% less likely (156 vs 88 per 10 000; RR, 0.57; 95% CI, 0.52-0.61) and daytime crashes decreased by 20% (951 vs 764 per 10 000; RR, 0.80; 95% CI, 0.78-0.83). Single-vehicle crashes (245 vs 175; RR, 0.71; 95% CI, 0.67-0.76) declined somewhat more than multiple-vehicle crashes (866 vs 681; RR, 0.79; 95% CI, 0.76-0.81).\n In its initial years, the North Carolina GDL system produced substantial declines in 16-year-old driver crashes.", "The rate of motor vehicle crashes in the United States is higher among adolescent drivers than among any other age group. This study was conducted to determine whether implementation of a graduated driver's licensing program is associated with a reduced the rate of motor vehicle crashes and injuries involving adolescent driver.\n Time periods before and after establishment of Delaware's GDL program were compared. The one year \"before\" period spanned January 1, 1998, through December 31, 1998, and the 3-year \"after\" period spanned January 1, 2000, to December 31, 2002. Following enactment of the GDL program on July 1, 1999, we delayed data collection during the \"after\" period for 6 months to allow for full implementation of the program. Information was obtained for all Delaware registered drivers between ages 16 and 17 years were involved in motor vehicle crashes involving property damage or injury from 1998 to 2002. The rate of crashes involving property damage, EMS transport, injury, hospitalization, and death were determined pre- and post-GDL,. Length of hospitalization and hospital charges were compared, and the presence and age of passengers, along with time of day were determined.\n The total number of licensed 16- and 17-year-old drivers in Delaware was 14,320 during 1998 (the before period), 16,849 for 2000, 14,098 for 2001, and 14,276 for 2002, for a total of 45,223 licensed drivers studied during the after period. The proportion of hospitalizations, injuries, crashes involving property damage and total number of crashes involving registered 16- and 17-year-old drivers after GDL each decreased by at least 30%. In addition, this GDL program was associated with a reduction in nighttime crashes and in crashes involving cars with multiple passengers in comparison with the time period before GDL.\n Two years after implementation, the hospitalization rate, injury rate, and crash rate decreased significantly with enactment of the GDL program in the State of Delaware. The Delaware's GDL program appears successful in decreasing motor vehicle crashes and resultant injuries in adolescent drivers.", "The purpose of this study was to measure the effectiveness of Wisconsin's graduated driver licensing law and determine whether a reduction in crash rates was due to reduced exposure, safer driving, or both.\n General population crash rates for 16 and 17 year olds were computed for years before and after graduated drivers licensing. The induced exposure method was used to measure exposure and compute the odds ratio of at-fault crash involvement.\n For 16 year olds, general crash rates declined 13.8% while injury crash rates declined 15.6%. For 17 year olds, crash rates declined 6.2% for all crashes and 5.8% for injury crashes. There was no statistically significant change in the odds ratio of at-fault crash involvement for 16- or 17-year-old drivers, relative to the reference group. After graduated drivers licensing, 16-year-old drivers were more likely to have at least 1 adult present and less likely to carry 2 or more teen passengers. There was no statistically significant effect on driving habits by time for 16 year olds.\n Graduated driver licensing in Wisconsin has resulted in a drop in the general population crash rates for 16 and 17 year olds. This decrease is the result of reduced exposure to the risk of collision rather than safer driving by teens.", "Young drivers have a disproportionately high risk of experiencing a road traffic crash. On 1 August 1987 a Graduated Driver's Licensing System (GDLS) was introduced in New Zealand. This system was designed to give young drivers (i.e. 15-24 years inclusive) experience in driving while being excluded from high risk driving situations. We sought to determine the impact of the GDLS on serious injury crashes. The source of the injury crash data was New Zealand's Health Information Services' national public hospital inpatient morbidity data files for the years 1979-1992 inclusive. We disaggregated the occupant data into three age groups 15-19 years, 20-24 years, and persons 25 years of age or older and compared their trends in injury. In order to determine whether the incidence of motor vehicle crashes was simply following trends in other injury events we also included two 15-19 year old non-traffic injury comparison groups. Using time series analyses we showed that the introduction of the GDLS was closely followed by substantial reductions in car crash injuries for all age groups, especially 15-19 year olds (23% reduction). After considering effects for older occupants we speculate that the effect is likely to be substantially less than 23%. An analysis of licensure data suggests that the reduction in crashes may, in large part, be attributable to an overall reduction in exposure." ]

[ "15296364" ]

[ "The effect of sesamoid mobilization, flexor hallucis strengthening, and gait training on reducing pain and restoring function in individuals with hallux limitus: a clinical trial." ]

[ "Clinical trial.\n To determine the effect of 2 conservative intervention approaches for functional hallux limitus.\n Metatarsophalangeal joint (MPJ) sprains are common and can result in long-term sequelae such as persistent pain and loss of range of motion (ROM) secondary to bony proliferation and articular degeneration. It is important to determine the most effective intervention for functional hallux limitus to decrease pain and restore function.\n Twenty individuals with first MPJ pain, loss of motion, and weakness participated in the study. All patients received whirlpool, ultrasound, first MPJ mobilizations, calf and hamstring stretching, marble pick-up exercise, cold packs, and electrical stimulation. Ten of the 20 patients (experimental group) also received sesamoid mobilizations, flexor hallucis strengthening exercises, and gait training. Treatment was provided 3 times a week for 4 weeks. Measurements of first MPJ extension ROM, flexor hallucis strength, and subjective pain level were performed on the first and last visits.\n Following the 12 therapy sessions, the experimental group achieved significantly greater MPJ extension ROM and flexor hallucis strength and had significantly lower pain levels as compared to the control group (P<.001).\n These results suggest that sesamoid mobilization, flexor hallucis strengthening, and gait training should be included in the plan of care when treating an individual with functional hallux limitus." ]

[ "11781276", "17565633", "16670529", "17764013", "12825868", "12524408", "12360457" ]

[ "Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up.", "Mesalazine with or without cholestyramine in the treatment of microscopic colitis: randomized controlled trial.", "Probiotic treatment of collagenous colitis: a randomized, double-blind, placebo-controlled trial with Lactobacillus acidophilus and Bifidobacterium animalis subsp. Lactis.", "Boswellia serrata extract for the treatment of collagenous colitis. A double-blind, randomized, placebo-controlled, multicenter trial.", "Incomplete remission with short-term prednisolone treatment in collagenous colitis: a randomized study.", "Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis.", "Budesonide treatment for collagenous colitis: a randomized, double-blind, placebo-controlled, multicenter trial." ]

[ "Collagenous colitis (CC) is a well-described entity causing chronic diarrhea and characteristic histologic findings. Several treatment options have been suggested, but no controlled data are available. We conducted a placebo-controlled trial to show the clinical and histologic effects of budesonide in CC.\n Twenty-eight patients were randomly assigned to receive placebo (n = 14) or budesonide 9 mg daily (n = 14) for 8 weeks. Patients were evaluated clinically, and blinded biopsy specimens were analyzed from fixed locations at weeks 0 and 8. Clinical response was defined as a decrease of at least 50% in the disease activity score (number of bowel movements in the last 7 days). At week 8, nonresponders received open-label budesonide for the next 8-week period; responders discontinued treatment and were followed up.\n Three patients discontinued the study prematurely. Intention-to-treat analysis showed clinical response in 8 of 14 patients in the budesonide group compared with 3 of 14 responders for placebo (P = 0.05) after 8 weeks of blinded therapy, together with improved stool consistency. Histologically, there was no change in the mean thickness of the collagen band but a significant decrease of the lamina propria infiltrate in the budesonide group (P < 0.001).\n Budesonide is efficacious in inducing short-term clinical response in CC with significant reduction of the histologic infiltrate in the lamina propria.", "Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory diseases of the colon with a benign and sometimes relapsing course. Frequency among patients with chronic diarrhea and normal looking colonoscopy is around 10-15%. To date, treatment of CC and LC is not well defined. Data about these conditions are mostly derived from retrospective studies. The aim of the present study was to evaluate the response to treatment and the clinical course of CC and LC in a large group of patients prospectively diagnosed.\n A total of 819 patients underwent a colonoscopy because of chronic watery diarrhea and among them we found 41 patients with LC and 23 with CC. These patients were later randomized and assigned to treatment with mesalazine or mesalazine + cholestyramine for 6 months. Fifty-four patients (84.37%) had resolved diarrhea in less than 2 weeks. After 6 months a colonoscopy with biopsies was repeated. Clinical and histological remission was achieved in 85.36% of patients with LC and in 91.3% with CC, with a better result in patients with CC treated with mesalazine + cholestyramine. During a mean period of 44.9 months, 13% of patients relapsed; four with LC and three with CC. They were retreated for another 6 months. At the end of this period one patient with CC was still symptomatic and persistence of CC was confirmed at histology.\n Treatment with mesalazine seems to be an effective therapeutic option for LC to date, while mesalazine + cholestyramine seems to be more useful in the treatment of CC.", "Probiotic treatment may be effective in diseases involving gut microflora and intestinal inflammation. In collagenous colitis (CC), a potential pathogenic role of the gut microflora has been proposed. The effect of probiotic treatment in CC is unknown. Our aim was to investigate the clinical effect of treatment with Lactobacillus acidophilus LA-5 and Bifidobacterium animalis subsp. lactis BB-12 (AB-Cap-10) in patients with CC.\n Patients with CC and diarrhea were in a double-blind placebo-controlled study randomized (2:1) to AB-Cap-10 or placebo for 12 weeks. The primary end point was reduction in bowel frequency per week of >or=50%. Secondary end points were changes in bowel frequencies, stool consistency, stool weight, histopathology, and abdominal bloating and pain.\n Twenty-nine patients were randomized: 21 to probiotics and 8 to placebo. Reduction in bowel frequency per week of >or=50% occurred in 6 of 21 (29%) and in 1 of 8 (13%) patients receiving probiotic and placebo, respectively (P = 0.635). No differences between treatments were observed regarding the secondary end points. Post hoc analysis showed a median reduction in bowel frequency per week from 32 (range 18-84) to 23 (range 11-56; P < 0.005), a reduction in number of days with liquid stools per week from 6 days (range 0-7 days) to 1 day (range 0-7 days; P < 0.005), and an increase in number of days with solid stools per week (P < 0.05) in the AB-Cap-10 group.\n AB-Cap-10 had no significant effect on the chosen end points. Post hoc analysis demonstrated amelioration of clinical symptoms in the AB-Cap-10 group, indicating that probiotic treatment may potentially influence the disease course of CC.", "The objective of this study was to investigate the effect of Boswellia serrata extract (BSE) on symptoms, quality of life, and histology in patients with collagenous colitis.\n Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral BSE 400 mg three times daily for 6 weeks or placebo. Complete colonoscopy and histology were performed before and after treatment. Clinical symptoms and quality of life were assessed by standardized questionnaires and SF-36. The primary endpoint was the percentage of patients with clinical remission after 6 weeks (stool frequency<or=3 soft /solid stools per day on average during the last week). Patients of the placebo group with persistent diarrhea received open-label BSE therapy for a further 6 weeks.\n Thirty-one patients were randomized; 26 patients were available for per-protocol-analysis. After 6 weeks, the proportion of patients in clinical remission was higher in the BSE group than in the placebo group (per protocol 63.6%; 95%CI, 30.8-89.1 vs 26.7%, 95%CI, 7.7-55.1; p=0.04; intention-to-treat 43.8% vs 26.7%, p=0.25). Compared to placebo, BSE treatment had no effect on histology and quality of life. Five patients discontinued BSE treatment prematurely. Discontinuation was due to adverse events (n=1), unwillingness to continue (n=3), or loss to follow-up for unknown reasons (n=1). Seven patients received open-label BSE therapy, five of whom achieved complete remission.\n Our study suggests that BSE might be clinically effective in patients with collagenous colitis. Larger trials are clearly necessary to establish the clinical efficacy of BSE.", "Microscopic colitis is a disease of unknown aetiology characterized by chronic watery diarrhoea and diarrhoea can be eliminated by budesonide but frequently recurs when budesonide is stopped. We studied whether prednisolone could induce remission in patients with disabling, chronic diarrhoea due to microscopic colitis.\n A double-blind, randomized (3:1) trial of oral prednisolone 50 mg daily or placebo for 2 weeks. Remission was defined as stool weight < or = 200 g/day or frequency < or = 2/day; effect was defined as > 50% reduction of either stool frequency or weight. Six centres screened 31 consecutive patients and included 11 with collagenous colitis and 1 with lymphocytic colitis. Median duration of diarrhoea was 9 months. Patients had a normal colonoscopy, and no evidence of coeliac disease, bile acid or lactose malabsorption. Patients with gastrointestinal infection, previous gastrointestinal surgery, abnormal biochemical screening or recent treatment with immunosuppressive agents were excluded.\n Stool weight (grams) declined in 7 of 9 patients given prednisolone and in 1 of 3 receiving placebo; changes in median weight were from 430 to 278 and from 825 to 489, respectively. Stool frequency (per day) declined from 6 to 3 and from 8 to 5. Remission was obtained in 2 and 0, and effect in 5 and 0, respectively (NS; Fisher exact test).\n Prednisolone 50 mg daily for 2 weeks induces incomplete remission in patients with chronic diarrhoea due to collagenous colitis.", "Collagenous colitis is characterised by diarrhoea, lymphocytic inflammation, and a thickened subepithelial collagen layer in the colorectal mucosa. No standard treatment of the disease is established.\n To investigate the clinical and histological effect of oral budesonide (Entocort, AstraZeneca) in the treatment of collagenous colitis.\n Twenty patients with collagenous colitis (collagen layer >10 micro m) and diarrhoea (>4 stools/day and/or stool weight >200 g/day).\n A randomised, double blind, placebo controlled trial of budesonide treatment. Patients were randomised to placebo or budesonide for eight weeks. Stool frequency and stool weight were registered before and after treatment. Sigmoidoscopy was performed before and after treatment, and biopsies at fixed locations were obtained for morphometric analysis.\n Ten patients were randomised to budesonide and 10 to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p<0.001). In the budesonide group, stool weight was reduced from 574 g/day to 200 g/day and stool frequency was reduced from 6.2/day to 1.9/day (p<0.01). The histological inflammation grade in the sigmoid mucosa and the thickness of the collagen layer were significantly reduced. A correlation between the grade of inflammation as well as collagen layer thickness and stool weight was found. No side effects were reported. Eight of 10 patients had relapse of symptoms within eight weeks after stopping treatment.\n Budesonide is a highly effective and well tolerated treatment of collagenous colitis. There is a high risk of relapse after stopping eight weeks of treatment.", "Collagenous colitis is an idiopathic microscopic colitis characterized by chronic watery diarrhea, a typical subepithelial collagen layer, and lymphoplasmacellular infiltration. We investigated the effect of budesonide on symptoms and histology in patients with collagenous colitis in a randomized, double-blind, placebo-controlled multicenter trial.\n Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral budesonide (Entocort capsules; AstraZeneca, Sodertalje, Sweden) 9 mg/day for 6 weeks or placebo. Complete colonoscopy was performed before and after treatment. Histopathology was assessed by a single pathologist blinded to the patients' treatment. Clinical symptoms were assessed by standardized questionnaires.\n Fifty-one patients were randomized; 45 patients were available for per protocol analysis. The rate of clinical remission was significantly higher (P < 0.001) in the budesonide group than in the placebo group (per protocol 86.9% vs. 13.6%, respectively; intention-to-treat 76.9% vs. 12.0%, respectively). Histologic improvement was observed in 14 patients of the budesonide group (60.9%) and in 1 patient of the placebo group (4.5%; P < 0.001). Two patients in the budesonide group (7.7%) and 1 patient in the placebo group (4.0%) discontinued treatment prematurely because of side effects.\n Oral budesonide (Entocort capsules) is an effective and safe treatment modality for patients with collagenous colitis. Long-term follow-up of these patients is necessary to investigate whether clinical and histologic remission is sustained." ]

[ "2155457", "3318442", "8064733", "3913558" ]

[ "[Quantitatively evaluated magnetic resonance tomography as a therapeutic follow-up of the nonsteroidal antirheumatic ademetionin: a pilot study in patients with gonarthrosis].", "Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease.", "A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis.", "Double-blind study of S-adenosyl-methionine versus placebo in hip and knee arthrosis." ]

[ "The report deals with a double-blind study of nine patients treated over a period of three months with either ademetionin (five patients) or with a placebo (four patients). Prior to treatment, and after three months, clinical and biochemical studies were carried out as well as radiological examinations and MRT. The latter had been standardised previously in order to obtain a cartilage signal which could be quantified. Of the five patients treated with ademetionin, none were improved clinically, two were worse and three were unchanged, but on MRT, three were improved, one was worse and one was unchanged. Amongst the placebo patients, the clinical results were: three improved, none worse and one unchanged, with similar findings on MRT. MRT appears to be useful for complementing the information for treatment planning with chondroprotective drugs.", "In a double-blind study, the efficacy and tolerability of S-adenosylmethionine (SAMe) were evaluated in comparison with those of placebo and naproxen in the treatment of osteoarthritis of the hip, knee, spine, and hand. Thirty-three centers, 18 rheumatologic and 15 orthopedic, participated in this study. A total of 734 subjects, including 582 with coxarthrosis (hip osteoarthritis) or gonarthrosis (knee osteoarthritis), were enrolled. SAMe administered orally at a dose of 1,200 mg daily was shown to exert the same analgesic activity as naproxen at a dose of 750 mg daily. Both drugs were more effective than placebo (p less than 0.01). Tolerability of SAMe was significantly better than that of naproxen, both in terms of physicians' (p less than 0.025) and patients' (p less than 0.01) judgments and in terms of the number of patients with side effects (p less than 0.05). There was no difference between SAMe and placebo in the number of side effects. Ten patients in the SAMe group and 13 in the placebo group withdrew from the study because of intolerance to the drug.", "We evaluated the effectiveness and rapidity of onset of S-adenosylmethionine (SAM), administered as daily intravenous boluses of 400 mg for 5 days, followed by oral tablets, 200 mg thrice daily for 23 days, versus a matching placebo regimen, in the treatment of 81 patients with symptomatic knee osteoarthritis (OA).\n The study was bicentric, randomized, double blinded, and placebo controlled. Patients underwent a 7-day washout of arthritis medications prior to initiation of this study treatment. Major outcome measures were the Stanford Health Assessment Questionnaire disability and pain scales, and supplemental visual analog scales for rest and walking pain.\n At one site, patients had milder OA, the baseline characteristics of the treatment groups were well matched, and the SAM treated group showed significantly greater reduction in overall pain and rest pain (p < 0.05) than the placebo treated group. At the other site, the patients had more severe OA, randomization yielded markedly different treatment groups, and the response to treatment did not differ between groups. Onset of SAM effect was seen as early as 14 days after the start of treatment.\n SAM may be an effective treatment for some patients with symptomatic knee OA, and merits further study. Intravenous loading before oral maintenance therapy may be advantageous.", "nan" ]

[ "2673337", "7442833", "12861170" ]

[ "Effect of external cephalic version in late pregnancy on presentation at delivery: a randomized controlled trial.", "[Is external version useful in breech presentation?].", "External cephalic version beginning at 34 weeks' gestation versus 37 weeks' gestation: a randomized multicenter trial." ]

[ "The effect of repeated external cephalic version, performed at between 33 and 40 weeks gestation, on presentation at delivery was studied in a randomized controlled trial comprising 180 pregnant women with breech presentation. No tocolysis, analgesia or anaesthesia was used. Approximately 25% of all attempts in the study group of 90 women were successful; repeated external version resulted in cephalic presentation at delivery in 48% of patients. Spontaneous version to cephalic presentation occurred in 23 (26%) of the 90 women in the control group in whom version was not attempted, indicating a therapeutic gain from the procedure of 22%, with a 95% confidence interval of 8 to 35%. No severe complications of external cephalic version were noted. We conclude that external cephalic version reduces the frequency of breech presentation at delivery. This mainly benefits the mother because of the decrease in the number of caesarean sections and their inherent maternal morbidity.", "nan", "In about 3% to 4% of all pregnancies at term, the fetal presentation will be noncephalic. External cephalic version (ECV) at term has been shown to decrease the rate of noncephalic presentation at birth and to decrease the rate of cesarean section associated with breech presentation. However, success rates for ECV are low. We did a randomized trial to compare a policy of beginning ECV early, at between 34 and 36 weeks' gestation, and beginning ECV at 37 to 38 weeks' gestation.\n At 25 centers in seven countries, 233 women with a singleton breech fetus were randomly assigned to having an ECV procedure done early (at between 34 weeks 0 days and 36 weeks 0 days), or delayed (at between 37 weeks 0 days and 38 weeks 0 days). An experienced practitioner undertook the ECV procedure, and repeat ECV procedures were allowed. Tocolytics and use of epidural analgesia were included as part of the protocol. The primary outcome was the rate of noncephalic presentation at birth. An intention-to-treat analysis was used.\n Data were received for 232 women, with 116 women in each of the early and delayed ECV groups. Of these, 86.2% in the early ECV group and 67.2% in the delayed ECV group had at least one ECV performed. The rate of noncephalic presentation at birth in the early ECV group was 66 of 116 (56.9%) and 77 of 116 (66.4%) in the delayed ECV group (relative risk [RR] [95% CI] 0.86 [0.70-1.05], P =.09). The rate of serious fetal complications and the rate of preterm birth at <37 weeks were not significantly increased in the early ECV group compared with the delayed ECV group (6.9% vs 7.8%, RR [95% CI] 0.89 [0.36-2.22], P =.69 and 8.6% vs 6.1%, RR [95% CI] 1.42 [0.56-3.59], P =.31, respectively). The rate of cesarean section in the early ECV group was 75 of 116 (64.7%) and 83 of 116 (71.6%) in the delayed ECV group (RR [95% CI] 0.90 [0.76-1.08], P =.32). Neonatal outcomes were comparable in the two groups. The rate of reversion to noncephalic was low in both groups. The majority of women in both groups indicated that they would consider having an ECV in another pregnancy.\n Early ECV performed at 34 to 36 weeks compared with 37 to 38 weeks may reduce the risk of noncephalic presentation at delivery. A large pragmatic trial of early ECV is now required to assess this approach further in terms of cesarean section rates and neonatal outcomes before changes in clinical practice." ]

[ "6364951", "6637313", "7827834", "1884733", "3081085", "3297230", "8759578", "8304606", "2044396", "3890435", "7603654", "10427881", "2645969", "9023498", "6738191", "9928687", "2341581", "2513026" ]

[ "Intravenous indomethacin in the treatment of ureteric colic. A clinical multicentre study with pethidine and metamizol as the control preparations.", "A comparative study on the analgesic effects of indomethacin and hydromorphinechloride-atropine in acute, ureteral-stone pain.", "A comparison of intramuscular ketorolac and pethidine in the alleviation of renal colic.", "Comparative study of the efficacy of dipyrone, diclofenac sodium and pethidine in acute renal colic. Collaborative Group of the Spanish Society of Clinical Pharmacology.", "Diclofenac sodium versus pethidine in acute renal colic.", "Intravenous indomethacin and oxycone-papaverine in the treatment of acute renal colic. A double-blind study.", "Comparison of intravenous ketorolac, meperidine, and both (balanced analgesia) for renal colic.", "Indomethacin suppositories versus intravenously titrated morphine for the treatment of ureteral colic.", "A multi-centre comparative study of diclofenac sodium and a dipyrone/spasmolytic combination, and a single-centre comparative study of diclofenac sodium and pethidine in renal colic patients in India.", "Comparison of a narcotic (oxicone) and a non-narcotic anti-inflammatory analgesic (indoprofen) in the treatment of renal colic.", "Intravenous tenoxicam for the treatment of renal colic.", "[Intramuscular ketorolac compared to subcutaneous tramadol in the initial emergency treatment of renal colic].", "Analgesic effect and tolerance of Voltaren and Ketogan in acute renal or ureteric colic.", "Comparative study of the efficacy of lysine acetylsalicylate, indomethacin and pethidine in acute renal colic.", "[Usefulness of a non-steroid anti-inflammatory, sodium diclofenac, in the treatment of renal colic. Comparative study with a spasmolytic and an opiate analgesic].", "Efficacy of ketorolac tromethamine versus meperidine in the ED treatment of acute renal colic.", "A double-blind single dose comparison of intramuscular ketorolac tromethamine and pethidine in the treatment of renal colic.", "Rectal diclofenac compared with pethidine injection in acute renal colic." ]

[ "The analgesic effects of intravenously administered indomethacin, pethidine and metamizol were compared in a series of 169 patients with ureteric colic. Complete pain relief was obtained in 59% in the indomethacin group, in 52% in the pethidine group and in 44% in the metamizol group. The observed side effects were not serious. On the basis of the study results indomethacin can be recommended as an alternative drug in the treatment of ureteric colic.", "In a prospective study, including fifty consecutive patients with acute ureteral-stone pain, the patients were randomly distributed into two groups for treatment. There were given either an intravenous injection of indomethacin (Confortid) 50 mg, or a subcutaneous injection of 2 mg hydromorphine chloride-atropine (Dilaudid-atropin 1 ml). Patients in the latter group also received a suppository of prochlorperazine (Stemetil) 25 mg. The analgesic effect of the two drugs did not differ significantly. Indomethacin was quicker acting, probably due to the intravenous route of administration. The side effects were alike but those caused by indomethacin had a tendency to be milder and of shorter duration.", "To compare the analgesic efficacy of a single 30 mg intramuscular dose of ketorolac with that of intramuscular pethidine 100 mg, in a double-blind, parallel-group investigation of patients presenting with pain suggestive of renal colic.\n Seventy-six patients (17 women, 15 men; mean age 45.2 years, range 20-80) were allocated by means of a pre-determined randomization schedule to receive ketorolac and 78 patients (20 women, 58 men; mean age 42.1, years range 18-70) to receive pethidine. Data from eight patients in the ketorolac group and six in the pethidine group were excluded from the efficacy analyses because of protocol violations. The severity of each patient's pain was assessed on a four-point verbal rating scale (VRS) and a 10 cm visual analogue scale at pre-dose and at 15 min intervals for the first hour post dosing. The time to first administration of rescue analgesic, up to 24 h following dosing with the study medication, was recorded. Adverse events were elicited by general questioning.\n Eighty-eight per cent of patients in each treatment group had improved according to the VRS of pain severity 1 h after dosing; the summed pain intensity differences up to 1 h were statistically significantly different in favour of ketorolac (P < 0.05). Fifty-six per cent of patients who were receiving ketorolac required rescue analgesia during the study period compared with 74% receiving pethidine. The incidences of adverse events were lower in the ketorolac group (28%) than the pethidine group (51%).\n Ketorolac can be considered a viable alternative to pethidine for the treatment of renal colic.", "A randomized, double-blind, multicentre clinical trial was designed to compared the analgesic efficacy of i.m. dipyrone 1 and 2 g, i.m. diclofenac sodium and i.m. pethidine in acute renal colic. The study was carried out in 451 patients in 13 Spanish hospitals. Ureteric colic was diagnosed by the clinical features, urinalysis, or when the presence of a ureteric calculus was confirmed. The severity of pain was assessed by the physicians and by patients using visual analogue scales. The main parameter of drug efficacy was the need for rescue treatment-pethidine 100 mg i.m. 30 min after the experimental treatment. Rescue treatment was required in 93 patients: they represented 24.1% of the group given dipyrone 1 g; 22.3% of those on dipyrone 2 g; 16.4% of those given diclofenac sodium; and 19.5% of those on pethidine. The differences between the groups were not significant. In the remaining 358 patients, no difference between treatments was observed. The results suggest that in acute renal colic the use of dipyrone 2 g is unjustified as dipyrone 1 g is equally effective. Diclofenac sodium is a valid alternative, which shows similar analgesic efficacy.", "nan", "In a prospective double-blind, cross-over study, 61 patients with acute renal colic were treated with either indomethacin (50 mg) or oxycone-papaverine (5 mg + 50 mg) administered intravenously. For those patients requiring a second injection the drugs were reversed. The intensity of pain was evaluated before and 20 min after each injection according to an analogue visual scale 0 to 100. Both drug regimens provided comparable and significant pain relief; a pain score of less than 20 appeared to be satisfactory and was achieved in almost all cases.", "To compare the analgesic efficacy and safety of IV ketorolac, the only nonsteroidal antiinflammatory drug indicated for parenteral use in acute pain in the United States, with IV meperidine and with a combination of the two agents in renal colic.\n We carried out a double-blind, randomized, multicenter clinical trial in the emergency departments of four urban tertiary care teaching hospitals. Our study subjects were 154 patients with suspected renal colic. Each subject received an initial IV dose of ketorolac 60 mg, meperidine 50 mg, or both supplemented as needed beyond 30 minutes with additional doses of meperidine.\n The main outcome measures were changes in pain-intensity and pain-relief scores, amount of supplemental meperidine required, end-of-study drug tolerability, and adverse events. Analyses of 106 subjects with confirmed renal colic indicated that ketorolac and the combination were significantly better than meperidine alone by all efficacy measures, including pain relief and time elapsed before the need for supplemental meperidine. By 30 minutes, 75% of the ketorolac group and 74% of the combination group had a 50% reduction in pain scores, compared with 23% of the meperidine group (P < .001). The ketorolac and combination groups did not differ significantly in any of the efficacy measures.\n IV ketorolac, alone or in combination with meperidine, was superior to IV meperidine alone in moderate and severe renal colic. Because many subjects in all three treatment groups received supplemental meperidine and because response to ketorolac alone cannot be predicted, clinicians may choose to initiate treatment with a ketorolac-meperidine combination.", "To develop a protocol for the blinded IV titration of morphine and to compare the analgesic efficacy and side effect profile of indomethacin suppositories versus IV morphine in the treatment of acute ureteral colic.\n Randomized, double-blind, double-dummy, two-period crossover study.\n Emergency department of a central-city, teaching hospital.\n Patients 18 to 75 years of age with pain suggestive of ureteral colic. Exclusions included pregnancy, adverse reactions to the study drugs, chronic nonsteroidal anti-inflammatory drug (NSAID) therapy, or any pain medicine taken within four hours of ED admission.\n Patients were randomized to one of two groups: indomethacin 100-mg rectal suppository or morphine by IV titration (5-mg loading dose and up to two additional 2.5-mg doses if needed). At the end of 30 minutes, if adequate pain relief had not been obtained, treatment was crossed over.\n Verbal analog scale (initial pain) and visual analog pain relief scale.\n Seventy-five patients were entered into the study. Only data from those patients with stone presence confirmed by IV pyelogram or stone passage were analyzed. Twenty-four could not be evaluated (23 who did not meet criteria for stone presence and one whose pain resolved spontaneously before study medications could be administered). Of the remaining 51 patients, 31 received indomethacin first and 20 received morphine first. Morphine recipients reported more pain relief at ten minutes (P = .02), but at 20 and 30 minutes, no significant difference (P = .17 and .74, respectively) existed between the two groups.\n IV morphine produced more rapid analgesia than rectally administered indomethacin. There were no significant differences in vital sign changes or number of side effects between the two treatment groups. This study is the first to compare an NSAID with morphine administered by IV titration, considered by many to be the \"gold standard\" for relief of acute, severe pain. Future studies could evaluate the simultaneous administration of an opioid combined with an NSAID or compare an IV titrated opioid with an IV NSAID.", "A single-blind, randomized clinical trial was carried out to compare the analgesic effectiveness in patients with renal colic of single intramuscular doses of diclofenac sodium (75 mg) versus a dipyrone (1 g)/spasmolytics combination, and diclofenac sodium (75 mg) versus pethidine (75 mg). The first study involved three centres, the second study one centre. In total, 107 patients were treated with diclofenac sodium, 85 with dipyrone/spasmolytics, and 25 with pethidine. Assessments were made during the first hour after drug administration of the degree of pain relief, the severity of pain using a visual analogue scale, and the duration of analgesia. A global assessment of treatment efficacy was made by the participating physicians at the end of the study period. Patients treated with diclofenac sodium showed an earlier onset of analgesia and a higher incidence of total pain relief compared to those treated with dipyrone/spasmolytics or pethidine. Although the mean duration of analgesia was only slightly greater in the diclofenac sodium group than in the dipyrone/spasmolytics group, a significantly longer effect was seen when diclofenac sodium was compared with pethidine (p less than 0.01). Pain severity assessments revealed that diclofenac sodium caused a significantly greater improvement in pain after 60 minutes compared to dipyrone/spasmolytics (p less than 0.05) and after 30 minutes compared to pethidine (p less than 0.05). Global efficacy assessments by the physician rated diclofenac sodium as significantly superior to dipyrone/spasmolytics (p less than 0.01) and pethidine (p less than 0.001). Moreover, diclofenac sodium was better tolerated than either of the comparative treatments. The results indicate that intramuscular diclofenac sodium is a useful alternative to the drugs commonly used in India in the treatment of renal colic.", "Intravenous indoprofen (400 mg), a cyclooxygenase inhibitor, was compared with intramuscular oxicodone hydrochloride (= oxicone 10 mg), a narcotic analgesic agent, in regard to efficacy and side effects in the treatment of renal colic. Oxicone was combined with papaverine (20 mg). Patients were randomized to either treatment, and the drugs were given in double-dummy fashion, i.e. one injection of active drug plus one placebo injection. Pain intensity before and after treatment was registered by the patient (visual analog scale) and by a nurse, who also registered side effects. Oxicone was given to 46 patients and indoprofen to 48. The groups did not differ in body weight, age, sex distribution, or pretreatment intensity of pain. More patients required additional treatment in the oxicone than in the indoprofen group (19 v. 10). At 2-5 min after injection, pain reduction was greater with indoprofen, and more patients in this group had pain relief after 3-5 hours. Side effects were less frequent with indoprofen than with oxicone (1 v. 20 patients), in particular from the central nervous system. This difference probably was related to indoprofen's slow and poor penetration of the blood-brain barrier. The study affirmed that non-narcotic cyclooxygenase inhibitors can replace narcotic analgesics for acute pain alleviation in renal colic. Indoprofen seems to be a useful alternative, with low risk of central nervous side effects.", "nan", "To compare the efficacy and safety of two analgesics (tramadol and ketorolac) for initial emergency treatment of renal colic.\n A prospective study on 48 patients randomly assigned to treatment with ketorolac 30 mg i.m. and tramadol 1 mg/kg s.c. Pain intensity was evaluated by a simple analogic scale ranging from 0-4 (0 = no pain, 1 = mild, 2 = moderate, 3 = severe and 4 = very severe pain). Statistical analyses were performed with Student's test and the chi square test for numerical and qualitative data, respectively.\n No significant differences were found for the overall efficacy (> 80%) or side effects in both groups. However, a difference was found between both groups for pain score 15 minutes post-injection, which showed i.m. ketorolac to be more effective.\n Both ketorolac (30 mg i.m.) and tramadol (1 mg/kg s.c.) are effective in the initial treatment of renal colic. Both drugs have an efficacy greater than 80% when used separately and almost 100% when used in combination. The analgesic effect of ketorolac is observed earlier than that of tramadol.", "Fifty-six patients with renal or ureteric colic were entered into a randomised, prospective, double-blind investigation of the analgesic efficacy and tolerance of Voltaren versus Ketogan, both administered intramuscularly. There were no significant differences regarding pain-relief but side effects were fewer in patients treated with Voltaren.", "The aim of this study was to compare the analgesic efficacy of intravenous lysine acetylsalicylate 1.8 g, indomethacin 100 mg and pethidine 100 mg in acute renal colic in a randomized double-blind clinical trial. One hundred and fifty patients with acute renal colic were divided into three groups. The first group received lysine acetylsalicylate 1.8 g, the second group received indomethacin 100 mg and the third group received pethidine 100 mg. The degree of pain relief was recorded 5, 15, 30 and 60 min after intravenous administration of the drugs. There was no statistically significant difference between the degree of analgesia provided by pethidine and indomethacin. Lysine acetylsalicylate was less effective than indomethacin and pethidine. It is concluded that intravenous indomethacin is an effective alternative to intravenous pethidine in the treatment of acute renal colic. Intravenous lysine acetylsalicylate is inferior to intravenous indomethacin in treatment of acute renal colic.", "nan", "To compare the efficacy of intramuscular ketorolac and meperidine in the emergency department (ED) treatment of renal colic, a prospective, controlled, randomized, double-blind trial was conducted in an academic ED with 76,000 annual visits. Participants were volunteer ED patients with a diagnosis of ureterolithiasis confirmed by intravenous pyelogram. Subjects were randomized 1:1 to receive a single intramuscular injection of either 60 mg ketorolac or 100 to 150 mg meperidine, based on weight. Of the 70 patients completing the trial, 33 received ketorolac and 37 received meperidine. Demographic characteristics and baseline pain scores of both groups were comparable (P = NS, Mann Whitney U). Ketorolac was significantly (P < .05) more effective than meperidine in reducing renal colic at 40, 60, and 90 minutes as measured on a 10-cm visual analogue scale. Similar proportions of patients in each group were given rescue analgesia and admitted. Of patients who were discharged home without rescue, those treated with ketorolac left the ED significantly earlier than those treated with meperidine (3.46 v 4.33 h, P < .05). These results show that intramuscular ketorolac as a single agent for renal colic is more effective than meperidine and promotes earlier discharge of renal colic patients from the ED.", "The efficacy of a single dose of intramuscular ketorolac 10 mg or 90 mg was compared with pethidine 100 mg in a randomized double-blind study in 121 patients reporting at least moderate pain due to renal colic. Pain was assessed before drug administration, and then at 1 hour and 12 hours after the dose. Sedation was also assessed at these times, and additionally at the 12 hour assessment the time of the next analgesic dose was recorded. At 1 hour after dosing, pain scores had decreased in all groups; the largest decrease was seen in the ketorolac 90 mg group. The difference in the decrease was significant between the two ketorolac groups, but the differences between ketorolac and pethidine were not significant. Fewer patients in the ketorolac 90 mg group (17%) required a further dose of analgesic within 10 hours than in either the ketorolac 10 mg group (39%) or the pethidine 100 mg group (47%). The difference between ketorolac 90 mg and pethidine 100 mg was statistically significant. At both assessment times the proportion of patients with no sedation was higher in the two ketorolac groups than in the pethidine group. The overall incidence of adverse events was low with all drugs, notably so for the occurrence of vomiting after ketorolac. The results of the study show that intramuscular ketorolac is efficacious in the treatment of renal colic.", "nan" ]

[ "17581289", "17940103", "11694668", "20075148" ]

[ "Effect of treadmill training with body weight support on gait and gross motor function in children with spastic cerebral palsy.", "Effects of intensity of treadmill training on developmental outcomes and stepping in infants with Down syndrome: a randomized trial.", "Treadmill training of infants with Down syndrome: evidence-based developmental outcomes.", "Effect of treadmill training and supramalleolar orthosis use on motor skill development in infants with Down syndrome: a randomized clinical trial." ]

[ "To examine the effect of treadmill training with body weight support (TBWS) on gait and gross motor function in children with spastic cerebral palsy (CP).\n Eight children with spastic CP participated in the study. Their temporal-distance gait parameters, Gross Motor Function Measure, muscle tone, and selective motor control were assessed three times: two times under their regular therapeutic treatment (condition A), and one time after receiving the TBWS treatment in addition to their regular therapeutic treatments (condition B). There were two treatment schedules, AAB and ABA. Except for the first one (taken at study entry), the assessments were always taken after 12 wks of treatment. The children were equally divided into two groups and randomly assigned to the two schedules. The two groups were matched according to category of the Gross Motor Function Classification System.\n The TBWS treatment significantly improved the children's gait (increases in stride length and decreases in double-limb support percentage of gait cycle) and their Gross Motor Function Measure (dimension D and E scores as well as the total score). No significant improvements on muscle tone or selective motor control were noted.\n The TBWS treatment improved some gait parameters and gross motor functions in children with spastic CP.", "Infants with Down syndrome (DS) are consistently late walkers. The purpose of this investigation was to test the effects of individualized, progressively more intense treadmill training on developmental outcomes in infants with DS.\n Thirty infants born with DS were randomly assigned to receive lower-intensity, generalized treadmill training or higher-intensity, individualized training implemented by their parents in their homes.\n Research staff members monitored implementation of training, physical growth, and onset of motor milestones of all infants on a monthly basis.\n Infants in the higher-intensity, individualized training group increased their stepping more dramatically over the course of training. Infants in the higher-intensity training group attained most of the motor milestones at an earlier mean age.\n Treadmill training of infants with DS is an excellent supplement to regularly scheduled physical therapy intervention for the purpose of reducing the delay in the onset of walking.", "On average, infants with Down syndrome (DS) learn to walk about 1 year later than nondisabled (ND) infants. The purpose of this study was to determine if practice stepping on a motorized treadmill could help reduce the delay in walking onset normally experienced by these infants.\n Thirty families of infants with DS were randomly assigned to the intervention or control group. All infants were karyotyped trisomy 21 and began participation in the study when they could sit alone for 30 seconds (Bayley Scales of Infant Development, Second Edition 1993, item 34). Infants received traditional physical therapy at least every other week. In addition, intervention infants received practice stepping on a small, motorized treadmill, 5 days per week, for 8 minutes a day, in their own homes. Parents were trained to support their infants on these specially engineered miniature treadmills. Every 2 weeks research staff went into the homes and tested infants' overall motor progress by administering the Bayley Scales of Infant Development, Second Edition, monitored growth status via a battery of 11 anthropometric measures, and checked parents' compliance with physical therapy and treadmill intervention. The primary measures of the intervention's effectiveness were comparisons between the groups on the length of time elapsed between sitting for 30 seconds (entry into the study) and 1) raising self to stand; 2) walking with help; and 3) walking independently.\n The experimental group learned to walk with help and to walk independently significantly faster (73.8 days and 101 days, respectively) than the control group, both of which also produced large effect size statistics for the group differences. The groups were not statistically different for rate of learning to raise self to stand but there was a moderate effect size statistic suggesting that the groups were meaningfully different in favor of the experimental group.\n These results provide evidence that, with training and support, parents can use these treadmills in their homes to help their infants with DS learn to walk earlier than they normally would. Current research is aimed at 1) improving the protocol to maximize outcome; 2) determining the impact of treadmill practice on walking gait patterns; 3) testing the application to other populations with a history of delays in walking; and 4) determining the long-term benefits that may accrue from this form of activity. motor development, Down syndrome, early intervention, walking.", "Children with Down syndrome (DS) often display delayed onset of independent walking. Treadmill training is an effective intervention that leads to an earlier walking onset. In addition, orthoses often are provided to infants with DS to increase stability and promote earlier independent walking. However, this early use of orthoses has not been scientifically verified in infants with DS.\n The purpose of this study was to provide insight into the developmental outcomes of early orthosis use in combination with treadmill training in infants with DS compared with treadmill training alone.\n This study was a randomized controlled trial.\n This study was conducted in participants' homes and in the motor development laboratory.\n Seventeen infants with DS entered the study when they could pull themselves to a standing position. They were randomly assigned to either a control group (which received treadmill training) or an experimental group (which received treadmill training and orthoses). During monthly visits to the infants' homes, 3 minutes of treadmill stepping was recorded and each child's motor development skills were tested. The treadmill training ended once the child took 3 independent steps. One month following walking onset, developmental tests were readministered.\n The Gross Motor Function Measure (GMFM) was used to test motor skill development.\n The average (SD) time in the study was 268 (88) days for the control group and 206 (109) days for the experimental group. All infants showed significantly increased GMFM scores over time. At 1 month of walking experience, the control group had higher GMFM scores than the experimental group, with higher standing and walking, running, and jumping subscale scores.\n Limitations of this study included a small sample of convenience, a statistical model that may have reduced validity at the tail end, and a lack of blinding in the GMFM scorer.\n Orthoses may have a detrimental effect on overall gross motor skill development." ]

[ "11276182", "10960936", "9239626", "3377664", "9442992", "12479619" ]

[ "Balance and mobility following stroke: effects of physical therapy interventions with and without biofeedback/forceplate training.", "Use of visual feedback in retraining balance following acute stroke.", "The development and clinical evaluation of a standing biofeedback trainer.", "Postural sway biofeedback: its effect on reestablishing stance stability in hemiplegic patients.", "Single blind randomized controlled trial of visual feedback after stroke: effects on stance symmetry and function.", "Effects of balance training on hemiplegic stroke patients." ]

[ "Visual biofeedback/forceplate systems are often used for treatment of balance disorders. In this study, the researchers investigated whether the addition of visual biofeedback/forceplate training could enhance the effects of other physical therapy interventions on balance and mobility following stroke.\n The study included a sample of convenience of 13 outpatients with hemiplegia who ranged in age from 30 to 77 years (mean=60.4, SD=15.4) and were 15 to 538 days poststroke.\n Subjects were assigned randomly to either an experimental group or a control group when the study began, and their cognitive and visual-perceptual skills were tested by a psychologist. Subjects were also assessed using the Berg Balance Scale and the Timed \"Up & Go\" Test before and after 4 weeks of physical therapy. Both groups received physical therapy interventions designed to improve balance and mobility 2 to 3 times per week. The experimental group trained on the NeuroCom Balance Master for 15 minutes of each 50-minute treatment session. The control group received other physical therapy for 50 minutes.\n Following intervention, both groups scored higher on the Berg Balance Scale and required less time to perform the Timed \"Up & Go\" Test. These improvements corresponded to increased independence of balance and mobility in the study population. However, a comparison of mean changes revealed no differences between groups.\n Although both groups demonstrated improvement following 4 weeks of physical therapy interventions, no additional effects were found in the group that received visual biofeedback/forceplate training combined with other physical therapy.", "Visual feedback related to weight distribution and center-of-pressure positioning has been shown to be effective in increasing stance symmetry following stroke, although it is not clear whether functional balance ability also improves. This study compared the relative effectiveness of visual feedback training of center-of-gravity (CoG) positioning with conventional physical therapy following acute stroke.\n Forty-six people who had strokes within 80 days before the study, resulting in unilateral hemiparesis, and who were in need of balance retraining participated.\n Initially, subjects were randomly assigned to visual feedback or conventional physical therapy groups for balance retraining until 16 subjects per group were recruited. The next 14 subjects were assigned to a control group. All subjects received physical therapy and occupational therapy (regular therapy) 2 hours a day, and subjects in the 2 experimental groups received additional balance training 30 minutes a day until discharge. The visual feedback group received information about their CoG position as they shifted their weight during various activities. The conventional therapy group received verbal and tactile cues to encourage symmetrical stance and weight shifting. Static (postural sway) and activity-based measures of balance (Berg Balance Scale, gait speed, and the Timed \"Up & Go\" Test) were contrasted across the 3 groups at baseline, at discharge, and at 1 month following discharge using an analysis of variance for repeated measures.\n All groups demonstrated marked improvement over time for all measures of balance ability, with the greatest improvements occurring in the period from baseline to discharge. No between-group differences were detected in any of the outcome measures.\n Visual feedback or conventional balance training in addition to regular therapy affords no added benefit when offered in the early stages of rehabilitation following stroke.", "A new standing biofeedback training device, which includes a height-adjustable work table, weight-bearing sensors, and a real-time visual and auditory feedback system, has been developed for postural training. Sixty persons with hemiplegia after acute stroke or traumatic brain injury were randomly divided into Group A (experimental) and Group B (control). After a training period of 4 weeks, the percentage of postural asymmetry in Group A and Group B was reduced from 17.2 +/- 10.8% and 17.0 +/- 10.0% to 3.5 +/- 2.2% and 10.1 +/- 6.4 percent, respectively (p = 0.003). There was no significant difference between subjects with right or left hemiplegia. The results indicated that this device had a positive training effect on stance symmetry in hemiplegic subjects.", "A static force plate system was used to examine postural sway characteristics in 16 hemiplegic patients and in 34 normal elderly subjects. The effectiveness of postural sway (center of pressure) biofeedback was compared to conventional physical therapy practices in reestablishing stance stability in hemiplegic patients. Postural sway abnormalities in hemiplegic patients included significant mean lateral displacement of sway towards the nonaffected leg and increased total sway area. Postural sway biofeedback was more effective than conventional physical therapy practices in reducing mean lateral displacement of sway. This was associated with increased loading of the affected leg. Posttreatment changes in total sway area were not significantly different between experimental and control groups.", "A number of before and after and single case design studies of visual feedback have shown improvements in stance symmetry after stroke, an associated improvement in function has been demonstrated. This study examines this promising technique further using a single-blind controlled trial. Twenty-six patients were recruited from a register of consecutive admissions and randomized into treatment and control groups. Both groups received additional therapy, only the treatment group received visual feedback. Assessments were carried out independently. Significant improvements were seen in the treatment group in measures of stance symmetry and sway and motor and ADL function. Between group differences had disappeared at three months. The results indicate that feedback training incorporated into functional physiotherapy treatment can improve stance symmetry and sway. Transfer of training was indicated by improvements in ADL and gross motor function. Three months later the improvement was maintained, but did not automatically continue without treatment.", "The purpose of this study was to evaluate the delayed effects of balance training program on hemiplegic stroke patients.\n A total of 41 ambulatory hemiplegic stroke patients were recruited into this study and randomly assigned into two groups, the control group and trained group. Visual feedback balance training with the SMART Balance Master was used in the trained group. Bruunstrom staging of affected limb scores and Functional Independent Measure (FIM) scores of each patient were recorded. Quantitative balance function was evaluated using the SMART Balance Master. Data were collected before training and 6 months after completing the training program.\n Significant improvements in dynamic balance function measurements were found for patients in the trained group at 6 months after completing the training program. The ability of self-care and sphincter control also improved for patients in the trained group. On the other hand, no significant differences were found in static balance functions between the trained group and control group at 6 months of follow up. The locomotion and mobility scoring of FIM also revealed no differences between the groups.\n Dynamic balance function of patients in the visual feedback training group had significant improvements when compared with the control group. Activities of daily living (ADL) function in self-care also had significant improvements at 6 months of follow up in the trained group. The results showed that balance training was beneficial for patients after hemiplegic stroke." ]

[ "10934074" ]

[ "Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis." ]

[ "We conducted a placebo-controlled, double-blind, randomized study to evaluate the microbiological efficacy and safety of inhaled tobramycin for treatment of patients with bronchiectasis and Pseudomonas aeruginosa. Patients were randomly assigned to receive either tobramycin solution for inhalation (TSI) (n = 37) or placebo (n = 37), which was self-administered twice daily for 4 wk and followed by 2-wk off-drug. At Week 4, the TSI group had a mean decrease in P. aeruginosa density of 4.54 log(10) colony-forming units (cfu)/g sputum compared with no change in the placebo group (p < 0.01). At Week 6, P. aeruginosa was eradicated in 35% of TSI patients but was detected in all placebo patients. Investigators indicated that 62% of TSI patients showed an improved medical condition compared with 38% of placebo patients (odds ratio = 2.7, 95% confidence interval [CI] 1.1 to 6.9). Tobramycin-resistant P. aeruginosa strains developed in 11% of TSI patients and 3% of placebo patients (p = 0.36). The mean percent change in FEV(1) percent predicted from Week 0 to Week 4 was similar for the TSI and placebo groups (p = 0.41). More TSI-treated patients than placebo patients reported increased cough, dyspnea, wheezing, and noncardiac chest pain, but the symptoms did not limit therapy. Additional study is warranted to further evaluate TSI in bronchiectasis patients." ]

[ "18325720" ]

[ "Computerized dietary assessments compare well with interviewer administered diet histories for patients with type 2 diabetes mellitus in the primary healthcare setting." ]

[ "To test repeatability and relative validity of a computerized and interviewer administered assessment.\n Using a context-based case-control trial, 41 adults with type 2 diabetes mellitus were randomized into four groups to complete dietary assessments (computerized or interviewer administered) at 0, 2 and 8 weeks and food records at 0 and 2 weeks. Repeatability of reported energy, total fat, saturated, polyunsaturated and monounsaturated fatty acids between the computerized and interviewer administered methods were assessed using repeated measures ANOVA. Paired t-tests and Pearson's correlations determined relative validity of the assessments.\n Thirty-one patients completed all visits. Statistically significant differences were found between computerized and interviewer administered data for total fat (p=0.048) and saturated fatty acids (p=0.019) between 0 and 2 weeks. Computerized assessments correlated better with food records (r=0.16-0.52) compared with interviewer administered assessments (r=-0.02 to 0.51).\n Computerized assessments saw a learning effect with repeated use indicating that users were becoming more familiar with the website with repeated use. Relative validity suggests that the website may capture more foods though this requires further investigation.\n By allowing patients to self-report their intakes on a computer, dietitians will have the ability to spend increased time with their patients counseling them toward change." ]

[ "3195535", "3303097", "15788528", "6737208" ]

[ "Physical and psychological effects of aerobic exercise in delinquent adolescent males.", "Influence of aerobic exercise training and relaxation training on physical and psychologic health following stressful life events.", "Improving physical fitness and emotional well-being in adolescents of low socioeconomic status in Chile: results of a school-based controlled trial.", "Influence of aerobic exercise on depression." ]

[ "Aerobic exercise has been associated with improved psychological status and physical fitness in adults, but its effects in adolescents have been less clear. This study evaluated the effects of aerobic exercise on the self-concept, depression level, and physical fitness of juvenile delinquents. Ninety-eight incarcerated youths who volunteered to participate were assigned in a blind fashion to one of two exercise programs lasting three months. Sixty-nine completed all phases of the study and are the subjects of this report. One exercise program (32 subjects) emphasized aerobic exercise; the other (37 subjects), limited exertion. Before and after participating, each subject underwent measurement of self-concept, mood, and physical fitness. While the aerobic and comparison groups were initially similar, the data demonstrated an association between participation in the aerobic exercise program and improved self-concept, mood, and fitness. Improvement in psychological variables was not dependent on improved physical fitness and was not related to preintervention measures.", "An experiment was conducted to determine whether aerobic exercise training or relaxation training would be effective for reducing the deleterious effects of life stress on physical and psychologic health. Over 1000 college students were surveyed, and 55 of those who reported experiencing a high number of negative life events over the preceding year were assigned to an aerobic exercise training condition, a relaxation training condition, or a no-treatment control condition. Physical and psychologic health were assessed with self-report measures before, halfway through, immediately following, and 8 weeks after the 11-week training (and control) period. Heart rate data collected during a treadmill test indicated that the aerobic exercise training was effective for improving cardiovascular fitness. Psychologic measures indicated that the exercise training condition was more effective than the other two conditions for reducing depression during the first 5 weeks of training. No differences were found among the conditions on self-report measures of physical health. These findings suggest that aerobic exercise training may be useful for reducing the severity and duration of depressive reactions following stressful life change.", "Regular physical activity is associated with a reduced risk of all-cause mortality, and mortality due to cardiovascular disease and cancer. Among adolescents, physical activity is associated with benefits in the prevention and control of emotional distress, and improvement of self-esteem. Countries in transitional epidemiological scenarios, such as Chile, need to develop effective strategies to improve physical activity as a way to face the epidemic of chronic diseases. The objective of this study was to evaluate the effects of a school-based physical activity program on physical fitness and mental health status of adolescents living in a low socioeconomic status area in Santiago, Chile. A quasi-experimental design was used to evaluate the effects of the program over one academic year. The study included 198 students aged 15 years old. Two ninth grade classes were randomly selected as the intervention group, with two classes of the same grade as controls. A social planning approach was used to develop the intervention. The program was designed and implemented based on student preferences, teachers' expertise and local resources. Changes in physiological and mental health status were assessed. After the intervention, maximum oxygen capacity achieved a significant increase of 8.5% in the intervention versus 1.8% in the control group (p < 0.0001). Speed and jump performance scores improved significantly more in the intervention versus the control group (p > 0.01). Anxiety score decreased 13.7% in the intervention group versus 2.8% in the control group (p < 0.01), and self-esteem score increased 2.3% in the intervention group and decreased 0.1% in the control group after the end of the program (p < 0.0001). No significant change was observed in the depressive score. Student participation and compliance with the program was > 80%. To conclude, a school-based program to improve physical activity in adolescents of low socioeconomic status, obtained a high level of participation and achieved significant benefits in terms of physical fitness and mental health status.", "Forty-three depressed women were randomly assigned to either (a) an aerobic exercise treatment condition in which they participated in strenuous exercise, (b) a placebo treatment condition in which they practiced relaxation exercises, or (c) a no-treatment condition. Aerobic capacity was assessed before and after the 10-week treatment period. Self-reported depression was assessed before, during, and after the treatment period. The results indicated that subjects in the aerobic exercise condition evidenced reliably greater improvements in aerobic capacity than did the subjects in either of the other conditions (p less than .002 in both cases) and that the subjects in the aerobic exercise condition evidenced reliably greater decreases in depression than did subjects in the placebo condition (p = .05) or subjects in the no-treatment condition (p = .001). These results provide the first controlled evidence concerning the effects of strenuous exercise on depression." ]

[ "20685865", "16084878", "16860045", "10232314", "7696821", "8003847", "21920189", "21664509", "8935460", "9649913", "18929731", "8443001", "10440332" ]

[ "Use of depot medroxyprogesterone acetate and fracture risk.", "Prior oral contraception and postmenopausal fracture: a Women's Health Initiative observational cohort study.", "Bone mineral density in women aged 25-35 years receiving depot medroxyprogesterone acetate: recovery following discontinuation.", "Oral-contraceptive use and risk of hip fracture: a case-control study.", "Risk factors for fractures of the distal forearm: a population-based case-control study.", "The effect of previous oral contraceptive use on bone mineral density in perimenopausal women.", "The association between oral contraceptive use, bone mineral density and fractures in women aged 50-80 years.", "Is the oral contraceptive pill associated with fracture in later life? New evidence from the Royal College of General Practitioners Oral Contraception Study.", "Risk factors, falls, and fracture of the distal forearm in Manchester, UK.", "Oral contraception and other factors in relation to hospital referral for fracture. Findings in a large cohort study.", "Fracture risk in very young women using combined oral contraceptives.", "Oral contraceptive pill use and fractures in women: a prospective study.", "Oral contraceptives and risk of hip fractures." ]

[ "Depot medroxyprogesterone acetate (DMPA), which has a high rate of use among teenagers in Europe and the United States, has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. Studies on the association between DMPA use and fracture risk are limited.\n We aimed at evaluating the relationship between use of hormonal contraceptives, specifically DMPA, and fracture risk.\n We conducted a case-control analysis using the United Kingdom-based General Practice Research Database.\n Participants were females aged 20-44 yr with an incident fracture diagnosis between 1995 and 2008.\n Odds ratios (OR) with 95% confidence intervals (CI) of incident fracture in relation to exposure to DMPA or combined oral contraceptives were assessed. Adjustments were made for smoking, body mass index, and additional potential confounders.\n We identified 17,527 incident fracture cases and 70,130 control patients (DMPA exposure: 11 and 8%, respectively). Compared with nonuse, current use of one to two, three to nine, or 10 or more DMPA prescriptions yielded adjusted OR for fractures of 1.18 (95% CI = 0.93-1.49), 1.36 (95% CI = 1.15-1.60), and 1.54 (95% CI = 1.33-1.78), respectively. Fracture risk was highest after longer treatment duration (>2-3 yr), and there was no difference in patients below and above the age of 30 yr. For users of combined estrogen-containing oral contraceptives, the OR were around 1.\n This population-based study suggests that use of DMPA is associated with a slightly increased risk of fractures.", "To test for the possible association of past oral contraceptive (OC) use and incident fracture after menopause.\n A prospective cohort of 93,725 postmenopausal women.\n Forty Women's Health Initiative (WHI) clinical centers across the United States.\n Ethnically diverse 93,725 volunteer postmenopausal women, 50 to 79 years old.\n None.\n The main outcome was self-reported incident first fracture assessed prospectively by annual questionnaire.\n The adjusted relative hazard (HR) for fracture among past OC users was 1.07 (95% CI, 1.01-1.15). Among women without any postmenopausal hormone treatment, past OC use for < or =5 years led to an HR of 1.15 (95% CI, 1.04-1.27) and for past OC use >5 years led to an HR of 1.09 (95% CI, 0.97-1.23) compared with never users.\n This study does not support the idea that past OC use protects against later fracture.", "This 7-year, prospective, matched-cohort, clinical study evaluated the effects of intramuscular depot medroxyprogesterone acetate (DMPA) (150 mg/mL) on bone mineral density (BMD) in women aged 25-35 years.\n Bone mineral density changes in new DMPA-IM users (n=248) were compared with those in women using nonhormonal contraception (n=360) for up to 240 weeks of treatment and 96 weeks of posttreatment follow-up (in subjects receiving >or=1 dose).\n At week 240 of treatment, mean percentage changes from baseline in DMPA-IM vs. nonhormonal subjects were: -5.16% (n=21) vs. +0.19% (n=65), total hip (p<.001); -5.38% (n=33) vs. +0.43% (n=105), lumbar spine (p<.001). At week 96 posttreatment, these values were: -0.20% (n=25) vs. +0.84% (n=43), total hip (p=.047); -1.19% (n=41) vs. +0.47% (n=66), lumbar spine (p=.017).\n These results show BMD declines during DMPA-IM use; following discontinuation, significant increases in BMD occur through 96 weeks posttreatment.", "Epidemiological studies indicate a protective effect of postmenopausal oestrogen therapy on the risk of osteoporotic fractures. Whether premenopausal oestrogen exposure in the form of oral contraceptives also reduces the risk of osteoporotic fractures remains uncertain.\n We did a population-based case control study of hip fracture among Swedish postmenopausal women, 50-81 years of age, through mailed questionnaires and telephone interviews. Of those women who were eligible, 1327 (82.5%) cases and 3312 (81.6%) randomly selected controls responded.\n 130 (11.6%) cases and 562 (19.1%) controls reported ever-use of oral contraceptives. Ever-use of oral contraceptives was associated with a 25% reduction in hip fracture risk (odds ratio 0.75 [95% CI 0.59-0.96]). Women who had ever used a high-dose pill (equivalent to > or = 50 microg ethinylestradiol per tablet) had a 44% lower risk for hip fracture than never-users (0.56 [0.42-0.75]). No overall trend was observed with duration of oral-contraceptive use, or time since last use. However, when making comparisons with women who have never used oral contraceptives, the odds ratios for hip-fracture were 0.69 (0.51-0.94) for use after age 40, 0.82 (0.57-1.16) for use at ages 30-39, and 1.26 (0.76-2.09) for use before age 30.\n Our results imply that in postmenopausal women, oral-contraceptive use late in reproductive life may reduce the risk of hip fracture, although we recognise the limitations of the case-control method.", "To evaluate the risk factors for early osteoporosis in consecutive patients with fracture of the distal forearm, a population-based case-control study was carried out using postal questionnaires supplemented by interviews when necessary. All men and women between the ages of 40 and 80 years who were resident in the County of Uppsala (population 265,000) and who sustained a fracture of the distal forearm during a defined 12-month period were initially included. Of 427 cases, 385 (90.2%) replied. Those with previous fragility fractures were excluded, leaving 367 patients in the study (mean age 61.9 +/- 10.6 years): 302 women (mean age 62.8 +/- 10.1 years) and 65 men (mean age 57.5 +/- 11.8 years). For each patient an age- and sex-matched control without previous fragility fractures was selected from the population register. The questionnaire concerned heredity, diseases and medications, general health, tobacco smoking and physical activity. Reproductive variables and postmenopausal hormone replacement therapy were analyzed extensively. In neither sex were any significant, consistent differences found with regard to chronic diseases, medications, physical activity or smoking. In females heredity for fractures (odds ratio, OR = 1.46) was associated with an increased risk. Nulliparous women had an increased risk of forearm fractures (OR = 1.72) while late menopause (OR = 0.95) and postmenopausal oestrogen therapy > 2 years (OR = 0.44) appeared to be protective. It is concluded that lifestyle factors did not discriminate between fracture patients and controls in this strict population-based investigation, suggesting that in affluent Western societies, with their high fracture rate, most individuals have an osteoporosis-prone way of life.(ABSTRACT TRUNCATED AT 250 WORDS)", "The bone mineral density (BMD) of the lumbar vertebrae L2-4 and femoral neck was determined by dual-energy X-ray absorptiometry (DXA) in 3222 perimenopausal women-a random stratified sample of the population-based Kuopio Osteoporosis Study (OSTPRE). The mean age of the women was 53.4 years (range 47.9-59.6 years). Twenty-nine percent of the women were past users of oral contraceptives (OC) containing 50 micrograms or less of ethinyl estradiol and 7.4% (n = 250) of the women reported OC use for more than 6 years. There was a slight but statistically significant difference between OC users (n = 939) and non-users (n = 2283) in lumbar BMD (1.134 +/- 0.155 g/cm2 v 1.123 +/- 0.161 g/cm2, p = 0.014). A statistically significant difference was recorded also after adjustment for years since menopause, duration of hormonal replacement therapy (HRT) and present weight (p = 0.044). When the analysis was performed among women who had never used oestrogen replacement therapy (n = 1427) and among premenopausal women (n = 387), no differences in BMD were found between OC users and non-users. Similarly, femoral neck BMD did not differ between the groups. This population-based study demonstrated a slightly higher lumbar BMD among past OC users. However, OC users and non-users differed from each other in many behavioral characteristics. Thus, the differences in BMD may be accounted for more by other factors than by past OC use itself. The low-dosage estrogen OCs used today would not be expected to have any positive bone effects among future perimenopausal women.", "The associations between oral contraceptive (OC) use, bone mineral density (BMD) and the risk of fractures remain controversial.\n A cross-sectional study of 491 women aged 50-80 years was performed. We assessed OC use and fractures by questionnaire, and BMD and vertebral deformity by dual-energy x-ray absorptiometry.\n Ever use of OC was associated with significantly higher BMD at the total body (6%, p<.001) and spine (4%; p=.05) (but not hip) after adjustment for confounders. There was also a significant association between duration of OC use and total body and spine BMD. Use of OCs for 5-10 years was associated with reduced vertebral deformity (adjusted odds ratio 0.46, 95% confidence interval 0.22-0.94).\n Oral contraceptive use and duration were associated with higher total body and spine BMD and a consistent reduction in vertebral deformities, although most associations did not reach significance.\n Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.", "Several studies, including an earlier analysis from the Royal College of General Practitioners (RCGP) Oral Contraception Study, have suggested that ever users of oral contraceptives have an increased risk of fracture when compared with never users. In this paper, we examined a subset of women in the RCGP study living in Scotland to determine whether this risk has persisted.\n A nested case-control study was carried out using data collected prospectively for the RCGP Oral Contraception Study. Cases were women with a first ever diagnosis of fracture (n=651), age-matched to two controls (n=1302). Adjustments were made for smoking, social class and parity.\n There was not a significant association between ever use of oral contraception and fracture (adjusted odds ratio 1.05, 95% confidence interval 0.86-1.29), compared with never users. Neither were significant associations found between fracture and smoking, social class and parity. The findings did not vary materially with age or type of fracture.\n Ever use of oral contraception was not associated with fracture in this study.\n Copyright © 2011 Elsevier Inc. All rights reserved.", "To determine the risk factors associated with fracture of the distal forearm, and to evaluate the influence of falls on these risks.\n This was a case-control study.\n Manchester, UK.\n The cases were 62 white women aged 45-82 years who had sustained a fracture of the distal forearm and had attended local hospitals. Two control groups were studied - 50 women who had fallen onto the hand but had not sustained a fracture (recruited from the same source as those with fracture) and 116 women randomly selected from primary care age and sex registers in the catchment area of the hospitals. Both cases and controls were sent a letter inviting them to take part in the study. Data were collected by questionnaire completed by an interviewer.\n Compared with the population control group, those with fracture were more likely to walk at a brisk pace (odds ratio (OR) = 3.5; 95% confidence interval (CI) 1.3, 9.6) though they had undertaken less physical activity at home or work on a daily basis throughout life (OR = 0.4; 95% CI 0.2, 0.9). The risk associated with brisk walking was less marked when the cases were compared with fall controls. Other lifestyle factors including calcium intake, smoking, and alcohol consumption were not associated with fracture. Analysis of gynaecological and hormonal factors suggested that compared with population controls, those with fracture of the distal forearm had had fewer fertile years (OR = 0.4; 95% CI 0.1, 0.9) and were less likely to have used oral contraceptives (OR = 0.3; 95% CI 0.1, 0.9).\n The data highlight the need for caution when advising middle aged and elderly subjects about exercise. Such advice should be combined with practical information about the prevention of falls. Hormonal factors seem to be additional determinants of fracture. Other lifestyle interventions seem unlikely to play an important part in preventing distal forearm fracture.", "There is good evidence that estrogens and progestogens have an important effect on bone metabolism. This article explores the relationship between oral contraceptive (OC) use and fractures occurring at various sites among the 17,032 participants in the Oxford-Family Planning Association contraceptive study, which now includes information accumulated during 310,000 woman-years of observation between 1968 and 1994. In total, 1308 women suffered at least one fracture during the follow-up period, which was largely confined to premenopausal years. When all fractures were combined, there was a modest, but highly significant trend (p < 0.001) of increasing risk with total duration of oral contraceptive use. In addition, there was statistically significant heterogeneity (p < 0.01) when overall fracture rates were examined in relation to recency of oral contraceptive use during the premenopausal lifespan. The highest relative risk (1.3, 95% CI 1.1-1.5) was for current or recent oral contraceptive users; however, viewed as a whole, no clear pattern of risk was apparent. Examination of the data for individual fracture sites (including the lower end of the radius/ulna) did not provide any evidence of a protective effect of oral contraceptive use. These results are closely similar to those reported from the Royal College of General Practitioners Oral Contraception Study in 1993.", "Little is known on fracture risk in young women using oral contraceptives.\n Case-control study (64,548 cases, 193,641 controls).\n Overall, no major association with risk of fracture was present. Only in a few age groups a limited increase (OR 1.1-1.5) was seen in those using low average doses (less than one tablet per day - i.e., intermittent use). Neither 20 nor >or=30 mcg per day of ethinylestradiol was associated with risk of fractures, while changing from 20 to >or=30 mcg per day or vice versa was associated with a limited increase in fracture risk (OR 1.1-1.4) in some age groups.\n In general, use of oral contraceptives in young women did not seem to be associated with an increased risk of fractures. The isolated increase seen in some strata with low average doses may be linked to factors associated with discontinuation of oral contraceptives rather than pharmacological effects.", "It has been suggested that use of the oral contraceptive pill by women confers protection against osteoporosis later in life. However, cross-sectional studies of bone density among pill users have yielded discrepant results. We therefore investigated the relationship between pill use and subsequent occurrence of fracture in a cohort of 46,000 women enrolled in the Royal College of General Practitioners Oral Contraception Study during 482,083 person-years of follow-up. Fracture risk was lower among multiparous women, non-smokers, and those of lower socio-economic class. The risk of subsequent fractures among the women who had ever used the oral contraceptive pill was significantly greater than that among women who had never used it (relative risk 1.20, 95% confidence intervals 1.08-1.34) after adjustment for these variables. When the analysis was confined to forearm fractures, no significant effect of pill use on fracture risk was detected. Although the study only includes limited observation of older women to date, these data do not support the hypothesis that pill use protects women against the occurrence of osteoporotic fractures in later life.", "nan" ]

[ "3289398", "6572335", "9307536", "7675378", "3094775", "8781697", "6374766", "7501332", "2646187", "6344644", "7936516", "2047061", "8598837", "1565347", "8610775", "9086420", "6932207", "1550148", "6945046", "7423284", "8796770", "2206072", "8064705", "3861138", "1738517", "17071427", "3478732", "1951503", "12521850", "2094145", "2564351", "1317643", "12521503", "1677625", "392623", "1554660", "1586330", "11883349", "6932208", "19065363", "371664", "9404911", "3855601", "8604599" ]

[ "Outpatient cervical ripening with prostaglandin E2 gel in uncomplicated postdate pregnancies.", "Cervical ripening with intravaginal prostaglandin E2 gel.", "Randomised trial of one versus two doses of prostaglandin E2 for induction of labour: 1. Clinical outcome.", "Premature rupture of membranes in nulliparas at term with unfavorable cervices: a double-blind randomized trial of prostaglandin and placebo.", "Prolonged pregnancy: the management debate.", "Randomised trial of outpatient induction of labor with vaginal PGE2 at 40-41 weeks of gestation versus expectant management.", "Endocervical prostaglandin E2 gel for preinduction cervical softening.", "A randomized trial of two preparations of vaginal prostaglandin for pre-induction cervical ripening.", "Is induction of labor indicated in prolonged pregnancy? Results of a prospective randomised trial.", "A comparison of prostaglandin E2 gel and prostaglandin F2 alpha gel for preinduction cervical ripening.", "Patient-administered outpatient intravaginal prostaglandin E2 suppositories in post-date pregnancies: a double-blind, randomized, placebo-controlled study.", "Sequential outpatient application of intravaginal prostaglandin E2 gel in the management of postdates pregnancies.", "Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group.", "Cervical ripening: a randomized study comparing prostaglandin E2 gel to prostaglandin E2 suppositories.", "Efficacy of outpatient induction with low-dose intravaginal prostaglandin E2: a randomized, double-blind, placebo-controlled trial.", "Outpatient management of the uncomplicated postdate pregnancy with intravaginal prostaglandin E2 gel and membrane stripping.", "A double blind dose trial of intravaginal prostaglandin F2 alpha for cervical ripening and the induction of labour.", "A randomized trial of prostaglandin E2 in a controlled-release vaginal pessary for cervical ripening at term.", "A simpler approach to labor induction using lipid-based prostaglandin E2 vaginal suppository.", "The induction of labour with prostaglandin E2 tablets administered intravaginally.", "Improved intravaginal controlled-release prostaglandin E2 insert for cervical ripening at term. The Prostaglandin E2 insert Study Group.", "Double-blind comparison of intravaginal prostaglandin E2 gel and \"chip\" for preinduction cervical ripening.", "Intravaginal prostaglandin E2 for cervical ripening and initiation of labor. Comparison of a multidose gel and single, controlled-release pessary.", "Intracervical versus intravaginal PGE2 for induction of labor at term in patients with an unfavorable cervix.", "An intravaginal controlled-release prostaglandin E2 pessary for cervical ripening and initiation of labor at term.", "Induction of labour at term with vaginal prostaglandins preparations: a randomised controlled trial of Prostin vs Propess.", "Maternal plasma bicycling PGE2 levels following vaginal administration of prostaglandin E2 pessaries in full term pregnancies.", "Patterns of uterine activity after intravaginal prostaglandin E2 during preinduction cervical ripening.", "Induction of labour: a comparison of two methods with particular concern to patient acceptability.", "Vaginal administration of PGE2 for induction of labor stimulates endogenous PGF2 alpha production.", "Cervical ripening with intravaginal prostaglandin E2 gel.", "Induction of labor by vaginal prostaglandin E2. A randomized study comparing pessaries with vaginal tablets.", "Is propess a better method of induction of labour in nulliparous women.", "A comparison of single prostaglandin E2 vaginal tablet with prostaglandin E2 vaginal pessaries for induction of labor at term.", "Controlled trial of induction of labor by vaginal suppositories containing prostaglandin E2.", "Role of prostaglandin in the management of prelabour rupture of the membranes at term.", "Prelabour rupture of the membranes at term and unfavourable cervix; a randomized placebo-controlled trial on early intervention with intravaginal prostaglandin E2 gel.", "A randomized trial of vaginal prostaglandin E2 for induction of labor. Insert vs. tablet.", "Use of vaginal prostaglandin gel before induction of labour.", "Comparison of Dinoprostone slow release pessary (Propess) with gel (Prostin) for induction of labour at term-a randomised trial.", "A comparison of PGE2 and PGF2 alpha vaginal gel for ripening the cervix before induction of labour.", "Premature rupture of membranes at term with an unfavorable cervix: comparison of expectant management, vaginal prostaglandin, and oxytocin induction.", "The effect of vaginal administration of various doses of prostaglandin E2 gel on cervical ripening and induction of labor.", "Local administration of prostaglandin E2 for cervical ripening and labor induction: the appropriate route and dose." ]

[ "A double-blind, placebo-controlled, prospective investigation was undertaken to determine whether the outpatient administration of prostaglandin E2 gel was helpful for ripening the cervix in postdate pregnancies. One hundred eighteen women with an uncomplicated pregnancy at or beyond 42 weeks' gestation with an unripe cervix (Bishop score less than or equal to 5) were randomly administered a single dose of gel containing either 2.5 mg prostaglandin E2 (n = 55) or a placebo (n = 63) before induction of labor with Pitocin. No side effects were detected in these healthy mothers and fetuses. A distinct change in Bishop score after 12 hours occurred more often in the prostaglandin E2 than in the placebo group (42% versus 6%, p less than 0.0001). Forty-four women (80%) who had received prostaglandin E2 were admitted in early labor; they required little or no oxytocin for augmentation. The duration of labor and maximum dose of oxytocin infused were significantly decreased in the prostaglandin E2 group, and forceps delivery or primary cesarean sections were performed less often when prostaglandin E2 was used (24% versus 44%, p less than 0.05). The outpatient administration of a single dose of prostaglandin E2 gel is safe in the uncomplicated postdate pregnancy and was found to significantly change the unripe cervix, enhance the onset of labor, minimize the need for oxytocin administration, and encourage a spontaneous vaginal delivery.", "Ripening of the cervix by intravaginal application of a prostaglandin-containing gel is evaluated. Thirty patients with an unfavorable cervix needing labor induction were studied in a double-blind, prospective fashion. The prostaglandin gel proved superior to placebo in ripening the cervix (P less than .05), reducing induction failures (P less than .025), diminishing the oxytocin dosage necessary for induction (P less than .05), and lowering the rate of cesarean section (.05 less than P less than .1). One hundred fifty additional patients with varying Bishop scores and differing clinical situations were also studied. There were 35 cesarean sections (23.3%), nine failed inductions (6%), a spontaneous labor rate of 46%, and an average Bishop score change of 2.5. Twenty patients with premature rupture of the membranes and an unfavorable cervix received a modified gel containing 2.5 mg of prostaglandin E2. Average Bishop score change was 2.9, and there was a 55% incidence of spontaneous labor.", "To compare the outcome of induction of labour using a single versus two doses of prostaglandin E2 vaginal gel.\n Prospective randomised trial comparing a single dose of prostaglandin E2 2 mg vaginal gel in the evening with two doses of prostaglandin E2 (2 mg), the second being given after six hours if labour had not started or the cervix was still unripe. Amniotomy and oxytocin titration were performed when necessary for both protocols. Nulliparae and multiparae were analysed separately by treatment intention.\n A maternity unit in a district general hospital annually delivering > 6000 women.\n Nine-hundred and ninety-five women with viable singleton pregnancies and cephalic presentation at term without previous history of caesarean section who were advised to have labour induced with prostaglandins.\n Need for formal amniotomy and oxytocin augmentation, use of epidural analgesia, rate of intrapartum interventions, mode of delivery and neonatal condition at birth.\n For multiparae two prostaglandin doses resulted in a significant reduction in the need for formal amniotomy (15% vs 30%) and oxytocin augmentation (28% vs 38%) compared with those receiving a single dose; there was no significant difference for nulliparae. Other interventions during labour, length of labour, and mode of delivery were similar in both protocols. Failed induction occurred only in nulliparae and was similar in both protocols (1%). There was no discernible difference in fetal or neonatal outcome although passage of meconium was more common in labour if two doses had been given, as was neonatal admission to the special care baby unit.\n There was little clinical benefit from inducing labour with two doses of prostaglandin E2 at a six-hour interval, compared with a single dose. There may be financial advantages with a two-dose regimen.", "To determine whether the use of a prostaglandin (PG) E2 3-mg pessary followed by a delay of 12 hours before stimulation of labor with oxytocin improves obstetric outcome compared with the use of a placebo pessary.\n One hundred fifty-five nulliparas at term with poor cervical scores (modified Bishop score below 6 of 10) and premature rupture of membranes (PROM) were recruited for this double-blind, placebo-controlled randomized trial. On admission to the study, either a PGE2 pessary or an identical-appearing placebo pessary was inserted into the posterior fornix. If labor did not start in the next 12 hours or if symptoms and signs of infection were evident, labor was induced with oxytocin infusion. Assignment was unblinded at the end of the study, and details of the labor and maternal and neonatal outcome in women who received a PG pessary were compared with those who received a placebo pessary.\n Women receiving a PG pessary were significantly less likely to require stimulation of labor at the end of 12 hours than were those given a placebo pessary (37 versus 58%, P = .002). The mean time between admission to study and delivery was significantly shorter in the PG group compared with the placebo group (15 versus 19 hours, P = .01). The rate of cesarean delivery was not statistically different in the two groups (13.9% with PG versus 15.8% with placebo).\n In nulliparas with poor cervical scores who present with PROM at term and no evidence of infection or obstetric complications, use of a PGE2 pessary resulted in more women establishing labor earlier, with a resultant reduction in the admission-to-delivery interval, compared with the use of a placebo pessary. The cesarean delivery rates in the two groups were similar, and there were no significant differences in neonatal outcome.", "A prospective trial was conducted to compare the effects of conservative management of prolonged pregnancy (conservative group) with routine induction of labour at 42 weeks' gestation (active group) in otherwise uncomplicated pregnancies. Of the 402 pregnancies studied, 207 (51%) were allocated to conservative management and 195 (49%) were allocated to have labour induced. The groups were well matched for age, parity, and smoking habits. One hundred and sixty six (80%) of the patients in the conservative group went into spontaneous labour. Of the remainder, two underwent elective caesarean section, 19 had labour induced because of clinical concern, and the remaining 20 had labour induced at the patient's own request. One hundred and twenty five (64%) of the patients in the planned active group underwent induction of labour. Of the remaining 70, 49 went into spontaneous labour and 21 (11%) asked that they should not have labour induced. Comparison of the two groups showed no difference in the length of the first stage of labour but a trend towards an increased need for intervention for fetal distress (p less than 0.06) in the active group. There were no differences in the length of the second stage, the need for intervention, or the mode of delivery. In terms of Apgar scores the neonatal outcome was not significantly different between the two groups, but a greater proportion of the babies (15% v 8%) in the active group required intubation. Umbilical cord venous pH estimated in the last 183 consecutive deliveries in the study showed a significantly lower mean value in the active group (p less than 0.05). There was no difference in birth weight between the two groups. Two deaths occurred in the study. There was a stillbirth in the conservative group at 292 days after massive abruption, and one neonatal death in the active group owing to multiple congenital abnormalities. The outcome for mother and baby in patients from both groups who went into spontaneous labour was generally good. The outcome for patients for whom conservative management was planned but induction became necessary was no different from that of patients who underwent planned induction at term. Thus from our results we can find no evidence to support the view that women with normal prolonged pregnancy should undergo routine induction of labour at 42 weeks' gestation.", "Two hundred consecutive women with uncomplicated pregnancies, at or within 4 days of their expected date of confinement, were prospectively randomized into 2 groups. One group had expectant management, with twice weekly surveillance tests, while the other group had 3 mg of vaginal prostaglandin E2 as outpatient treatment. There were 104 women in the expectant group and 70 in the induction group (26 women allocated to induction preferred no treatment). The average number of days to delivery was 1.6 in the induction group and 5.2 in the expectant group (p < 0.001). While meconium was much less frequent in the induction group (p < 0.002), all other outcome measures, including cesarean section rates, incidence of macrosomia, and Apgar scores, were similar in the two groups.", "A single, endocervical application of a new commercial preparation of prostaglandin E2 (PGE2) gel, 0.5 mg of PGE2 in 2.5 ml (3 g), was evaluated for preinduction cervical softening. Safety and efficacy were assessed in a comparison with a 2.0 mg PGE2 vaginal tablet and placebo in normal nulliparous women at term, with low Bishop scores. Treatment was administered in randomized, double blind fashion. Overall success, defined as a progression in Bishop score of at least 3 points within 12 hours, was achieved in 22/40 (55%) of the gel group, 15/41 (37%) in the tablet treated women, and 8/40 (20%) in those receiving placebo. Of interest was the observation that of women with very unfavorable induction features (Bishop score 0-2), the cervical gel treatment resulted in a 6/8 (75%) success rate compared with 2/13 (15%) success for the vaginal tablet and 0/17 (0%) for placebo. In as much as a very low incidence of side effects accompanied this treatment scheme, expanded multi-center testing is recommended.", "To compare two prostaglandin (PG) E2 preparations for pre-induction cervical ripening in a randomized clinical trial.\n Two milligrams of vaginal PGE2 gel was compared with a vaginal PGE2 3-mg tablet in 200 nulliparous women. Outcomes assessed were induction failure, need for labor augmentation, pain relief requirements, fetal heart rate (FHR) abnormalities, operative delivery rate, induction-to-delivery interval, neonatal condition, and occurrence of uterine hyperstimulation.\n There was no statistical difference in pre- and post-dose cervical scores. Compared with the tablet group, women in the gel group were more likely to have significant FHR abnormalities in early labor (odds ratio [OR] 4.77, 95% confidence interval [CI] 1.15-19.5) requiring cesarean delivery. Fetal heart rate tracings in the active phase of labor were also more likely to be abnormal in the gel group (chi 2 = 4.31, P < .05). Compared with the gel group, women in the tablet group were significantly more likely to require operative delivery for poor progress in labor (OR 2.83, 95% CI 1.20-7.24). Other clinical outcomes were identical, with no significant differences in the overall rate of failed induction, cesarean delivery, rate of assisted delivery, requirement for oxytocin infusion, induction-to-delivery interval, pain relief requirements, or neonatal condition.\n When compared with the PGE2 tablet, the use of PGE2 gel for cervical ripening and labor induction in nulliparous women did not result in significant improvements in labor outcome. Whereas the gel was associated with an increase in significant FHR abnormalities, the tablet was associated with an increase in the rate of operative delivery for poor progress in labor.", "In 345 women with a favorable cervical score at due date, labor was either induced by means of intravaginal application of tablets containing 3 mg of prostaglandin E2 or spontaneous onset of labor was awaited until the 42nd week of pregnancy. Eighty percent of the nulliparae and 96.3% of the multiparae of the induction group gave birth within 24 h of the administration of the first tablet. All pertinent delivery intervals were significantly shorter in this group compared to those women where spontaneous onset of labor was awaited. The rate of operative deliveries was lower in the induction group. With the exception of 1 fetal death 3 days after due date, fetal outcome was excellent in both groups. Elective induction was at least equivalent to awaiting the onset of spontaneous labor and was not associated with higher complication rates due to the method of induction.", "The unfavorable cervix remains a major obstacle to the successful induction of labor. Reported are results from an ongoing study of topical prostaglandin preparations used to effect preinduction cervical ripening. The current study compares the efficacy of 40 mg of prostaglandin (PG) F2 alpha versus 5 mg of PGE2, applied to the cervix in a methyltylose gel the night before attempted induction of labor. A prospective double-blind protocol was used similar to that which previously established the efficacy of the 5 mg of PGE2 preparation versus placebo at this institution. Results indicate the superiority of the PGE2 preparation as measured by change in Bishop score, Pitocin requirement, rate of cervical dilatation, and percentage of failed inductions. Cesarean section rates were similar in the two study groups, and no fetal or maternal morbidity was attributable to the preinduction ripening technique.", "To shorten post-date pregnancies in a safe, effective manner by outpatient acceleration of cervical ripening.\n Eighty patients with uncomplicated pregnancies at or beyond 41 weeks' gestation and a cervical Bishop score less than 9 were randomized to daily self-administered, 2-mg intravaginal prostaglandin E2 (PGE2) or placebo suppositories. Each followed a standard post-date antepartum surveillance protocol. Patients were admitted for spontaneous labor or for induction if the Bishop score reached 9, antepartum testing was nonreassuring, exclusion criteria were fulfilled, or if the gestational age reached 44 weeks.\n Fewer suppositories were used in the PGE2 group (four versus seven; P = .006), resulting in earlier gestational age on admission (295 versus 297 days; P = .021) and lower antepartum testing charges ($476.97 versus $647.29; P = .001). Labor and delivery time was significantly decreased in nulliparas (10.7 +/- 5.1 versus 15.3 +/- 7.6 hours; P = .035).\n Daily low-dose, patient-administered PGE2 vaginal suppositories can decrease the gestational length and cost of uncomplicated post-date pregnancies by reducing the time to achieve a favorable cervix, the need for antepartum testing, and, potentially, post-date-related complications.", "A randomized blinded investigation was undertaken to determine the efficacy and safety of sequentially applied intravaginal prostaglandin E2 (PGE2) gel for accelerating cervical ripening in an outpatient setting in low-risk prolonged pregnancies. Fifty women with uncomplicated pregnancies at or beyond 41 weeks' gestation and Bishop scores below 9 received twice-weekly outpatient administration of gel containing 2.0 mg of PGE2 or placebo. Thirty nulliparas and 20 multiparas were enrolled. The PGE2 gel failed to improve cervical ripening over placebo, as judged by Bishop scores. There was no difference between the groups in gestational age on admission to the labor and delivery suite, number of gel applications, requirement for oxytocin, incidence of cesarean delivery, or neonatal outcome. Only two patients (4%) experienced regular uterine contractions after gel insertion; these subsided spontaneously in both. None of the subjects experienced labor, tetanic contractions, evidence of fetal distress, or any other side effects related to gel insertion. We conclude that PGE2 gel in this dosage may be used safely in an outpatient setting, but more frequent application or earlier initiation may be required to produce a clinical effect.", "As the interval between rupture of the fetal membranes at term and delivery increases, so may the risk of fetal and maternal infection. It is not known whether inducing labor will reduce this risk or whether one method of induction is better then another.\n We studied 5041 women with prelabor rupture of the membranes at term. The women were randomly assigned to induction of labor with intravenous oxytocin; induction of labor with vaginal prostaglandin E2 gel; or expectant management for up to four days, with labor induced with either intravenous oxytocin or vaginal prostaglandin E2 gel if complications developed. The primary outcome was neonatal infection. Secondary outcomes were the need for cesarean section and women's evaluations of their treatment.\n The rates of neonatal infection and cesarean section were not significantly different among the study groups. The rates of neonatal infection were 2.0 percent for the induction-with-oxytocin group, 3.0 percent for the induction-with-prostaglandin group, 2.8 percent for the expectant-management (oxytocin) group, and 2.7 percent for the expectant-management (prostaglandin) group. The rates of cesarean section ranged from 9.6 to 10.9 percent. Clinical chorioamnionitis was less likely to develop in the women in the induction-with-oxytocin group than in those in the expectant-management (oxytocin) group (4.0 percent vs. 8.6 percent, P<0.001), as was postpartum fever (1.9 percent vs. 3.6 percent, P=0.008). Women in the induction groups were less likely to say they liked \"nothing\" about their treatment than those in the expectant-management groups.\n In women with prelabor rupture of the membranes at term, induction of labor with oxytocin or prostaglandin E2 and expectant management result in similar rates of neonatal infection and cesarean section. Induction of labor with intravenous oxytocin results in a lower risk of maternal infection than does expectant management. Women view induction of labor more positively than expectant management.", "Prostaglandin (PG) E2 has proven effective in many studies as a pre-induction agent for cervical ripening. The purpose of this study was to compare the efficacy of a 5-mg dose of PGE2 prepared gel with that of a quartered PGE2 20-mg suppository. Previous studies have documented uniform distribution of PGE2 in the suppository. After 90 patients entered the study, there appeared to be an unacceptable rate of hyperstimulation following the induction dose using the suppository. The study was discontinued, and data analysis revealed a 24% hyperstimulation rate with the quartered suppository versus 0% with the gel. The successful vaginal delivery rates were equivalent, at 75% for the gel and 66% for the suppository. The 5-mg quartered suppository appeared to initiate an unacceptable amount of uterine activity, much greater than with the 5-mg gel dose.", "Our purpose was to determine whether a protocol for outpatient induction is safe and effective for initiating labor.\n A randomized, double-blind, placebo-controlled trial was performed with 100 low-risk patients having well-dated pregnancies. Women with a Bishop score < or = 6 at 38 to 40 weeks' gestation were administered either 2 mg of intravaginal prostaglandin E2 gel or placebo for 5 consecutive days as outpatients while undergoing fetal monitoring.\n The median interval from randomization to delivery was 4 days in the prostaglandin E2 group (range 0 to 28 days) versus 10 days in the placebo group (range 0 to 26 days, p = 0.002). Twenty-seven of 50 patients (54%) in the prostaglandin E2 group were admitted for labor during the dosing interval compared with 10 placebo-treated patients (20%, p = 0.001). The mean gestational age at delivery was significantly reduced in the treatment group (39.9 +/- 1.0 weeks vs 40.5 +/- 0.99 weeks, p = 0.003) as was the incidence of postdates pregnancy (40% vs 66%, p = 0.016). Hyperstimulation was observed in one prostaglandin E2-treated patient, but no intervention was required.\n Outpatient low-dose prostaglandin E2 gel administration is effective for initiating labor in patients with an unfavorable cervix and appears safe if performed with adequate monitoring.", "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.", "nan", "The purpose of this study was to determine if prostaglandin E2 in a controlled-release vaginal pessary can produce cervical ripening at term.\n This was a double-blind, randomized, placebo-controlled study conducted at a university center and involving 81 patients with 42 receiving active agent. Categoric data were analyzed by Pearson's chi 2 or logistic regression. Continuous variables were analyzed by analysis of variance and the F test.\n Prostaglandin E2 was significantly better than placebo at cervical ripening and at decreasing the time to rupture of membranes, the time to onset of labor, the need to give oxytocin, and the time to vaginal delivery. Multiparous women benefitted more than primiparous ones. The cesarean section rate decreased only for multiparous women. Uterine hyperstimulation occurred only with prostaglandin E2 and after the onset of labor.\n Prostaglandin E2, when administered in a controlled-release vaginal pessary, is affective in producing cervical ripening at term. This agent should be used on inpatients who are under continuous monitoring and it should be removed at the onset of labor.", "The outcome of labor induced by use of a glyceride-based vaginal suppository of prostaglandin E2 (PGE2) inserted 3 hours before amniotomy, when the cervix is favorable, has been assessed. Using 5 mg PGE2 for primigravidas and 2.5 mg for multigravidas, 63% of the former and 81% of the latter established labor and were delivered of their infants without oxytocin augmentation, allowing ambulation during early labor. No maternal complications were detected as a result of the PGE2 treatment. Compared with patients undergoing conventional induction by amniotomy and immediate oxytocin titration there was no difference in the duration of labor, with a few patients establishing labor and giving birth quickly with both induction methods. Fetal distress was less common following PGE2 treatment than following conventional induction, with three patients in each group requiring delivery by cesarean section. Cephalopelvis disproportion in the second stage of labor requiring cesarean section to deliver occurred more frequently in the prostaglandin-treated group, possibly as a result of reduced upper segment contractility in the first stage of labor with subsequent poor fetal head molding. Epidural analgesia and postpartum hemorrhge were both reduced following PGE2-induced labor.", "Prostaglandin E2 tablets administered vaginally succesfully induced labour in 64% of patients. There were no maternal or fetal complications. Comparison of the Bishop score failed to identify any factors which significantly influenced the success rate.", "The purpose of this study was to determine if prostaglandin E2 (PGE2) in a controlled-release vaginal insert with retrieval system can produce cervical ripening at term. This was a multicenter, double blind, randomized, placebo-controlled study involving 206 patients with 102 receiving active agent. A successful outcome was defined as a change in Bishop score of > or = 3, or a Bishop score of > or = 6 at 12 h or delivery within 12 h of the insert placement. Analysis was by Fisher's exact test, Wilcoxon's two-sample rank-sum test, and Student's t-test where appropriate. One hundred ninety-three women completed the protocol. Initial Bishop scores were 2.6 +/- 1.2 and 2.5 +/- 1.4 in the PGE2 and placebo groups, respectively. The incidence of cesarean delivery was identical in the two groups. Uterine hyperstimulation lasted 2-13 min in 5 PGE2 patients (4.9%) with 1 patient requiring tocolysis. More patients in the PGE2 group had a change in Bishop score of > or = 3 (62% vs. 40%; P = 0.002), a Bishop score > or = 6 after 12 h (46% vs. 34%; P = 0.11), and vaginal delivery within 12 h (6.5% vs. 1%; P = 0.055). Sixty-five percent of PGE2 group patients had a successful outcome vs. 44% of control patients (P = 0.001). In conclusion, when administered in a controlled-release vaginal insert with a retrieval system, PGE2 is effective in promoting cervical ripening at term.", "The intravaginal application of prostaglandin E2 for preinduction cervical ripening has proved to be advantageous in the management of patients with an unfavorable cervix. The purpose of this double-blind randomized investigation was to compare the efficacy and safety of two methods of prostaglandin E2 delivery. Patients who were to have preinduction cervical ripening because of an unfavorable cervix (Bishop score less than or equal to 4) were randomly assigned to be given a single dose of prostaglandin E2 as either 2.5 mg of gel or a 3.0 mg \"chip\" intravaginally in a placebo-controlled manner. Sixty-nine patients received the active prostaglandin E2, 34 in the gel group and 35 in the \"chip\" group. The groups were similar in maternal age, race, parity, gestational age, and initial Bishop score. Both forms of prostaglandin E2 were easy to administer and helpful in priming an unfavorable cervix. The need for, duration of, and maximum dose of oxytocin were similar in both groups. Cesarean delivery because of failed induction occurred in 5 of 35 (14.3%) patients receiving a \"chip\" and 4 of 34 (11.8%) receiving the gel. However, patients receiving a \"chip\" experienced a 20% (7/35) incidence of hyperstimulation, compared with 2.9% (1/36) in those receiving the gel (p less than 0.05). The only case requiring immediate cesarean delivery because of intractable uterine hyperstimulation received a \"chip.\" We conclude that both methods were effective for cervical ripening, but the lower incidence of uterine hyperstimulation seen with the gel would suggest that it is preferable to the \"chip.\"", "A study was conducted to compare the efficacy and safety of two methods of delivering prostaglandin E2 (PGE2) as a low-dose gel delivered in up to two sequential, 2.5-mg doses and as a single-dose, controlled-release, 10-mg pessary. A cervical change was present in both groups, but a Bishop score > or = 8 occurred in more nulliparous patients in the pessary than in the gel group by 12 hours after dosing. Labor was initiated without oxytocin more frequently in the pessary than gel group for nulliparas and multiparas. Reversal of uterine hyperstimulation was possible by removal of the pessary without tocolytic therapy. The controlled-release PGE2 pessary was more effective in changing the cervix in nulliparas and in initiating labor and offered the advantage of removal when desired.", "In a randomized double-blind study we evaluated the effects on cervical ripening and labor induction of 0.5 mg PGE2 in gel given intracervically and 2.0 mg PGE2 given as a vaginal suppository. All patients were at term with unfavorable cervical scores. The indications for induction were toxemia, diabetes mellitus, Rh-immunization, or intrauterine growth retardation. Significantly better results for both cervical priming and labor induction were obtained after intracervical PGE2-gel application than after treatment with placebo or vaginal suppositories. Eleven out of 19 patients (58%) were delivered within 24 h after intracervical PGE2-gel compared to two out of 19 patients given placebo (p less than 0.01). In patients not delivered 24 h after the start of treatment, the mean cervical score had changed from 3.7 to 6.0 (p less than 0.05) after PGE2-gel application compared to a change from 3.9 to 4.3 after placebo treatment (n.s.). The outcome after treatment with PGE2 suppositories did not differ significantly from that with placebo treatment. In a subsequent study 25 patients were given 0.5 mg PGE2-gel intracervically. The results were consistent with those obtained in patients receiving PGE2-gel intracervically in the double-blind study. Few side effects were noted. No patient complained of gastro-intestinal discomfort but increased myometrial activity was observed in two patients; one after placebo and the other after active intracervical PGE2-gel treatment. The hyperactivity was readily countered with the beta 2-agonist, terbutaline. All infants were born in good condition with Apgar scores of 7 or more within 5 min. At pediatric examinations at 1 week and at 6 months of age all children seemed healthy.", "The purpose of this randomized, double-blind study was to evaluate the efficacy and safety of a new controlled-release hydrogel pessary for ripening the cervix and initiating labor. Subjects had an entry Bishop score of 4 or less and gestational age of 37 or more weeks. One hundred fourteen women received a placebo pessary and 101 received the hydrogel pessary, containing 10 mg of prostaglandin (PG) E2. Compared with the placebo group, those given the PGE2 pessary were more likely to have an increase in Bishop score of 3 or more (60 or 59% versus 21 or 18%; P less than .0001), change to a Bishop score of 6 or higher (59 or 58% versus 18 or 16%; P less than .0001), and active labor (68 or 67% versus 15 or 13%; P less than .0001). Including the crossover study, uterine hyperstimulation (28 of 182, 15%) and fetal heart rate abnormalities (18 of 182, 10%) in PGE2-treated subjects were reversed on removal of the pessary with no apparent harm to the mother or fetus. These temporary adverse effects appeared while the pessary was in place and after the onset of active labor. Oxytocin was unnecessary in 89 of 182 (49%) of the PGE2-treated cases and was used more often to augment than to induce labor. We conclude that the described controlled-release PGE2 vaginal pessary induces appreciable cervical ripening and frequently initiates active labor with little or no need for oxytocin. The pessary may cause uterine hyperstimulation or fetal heart rate abnormalities, but these would be expected to reverse on removal of the pessary.", "The purpose of the trial was to determine whether a sustained release preparation of prostaglandin E2 (Propess) is better in inducing labour when compared with the more widely used short-acting (instant-release) preparation (Prostin). A randomised controlled clinical trial involving 100 pregnant women at term with an indication for induction of labour was conducted in a district general hospital in the UK over a 1-year period. Women were randomised to receive one of the two preparations. The study revealed that there was no statistically significant difference in time to onset of labour, duration of labour, total time from induction to delivery, method of delivery, and analgesia requirements. The number of preparations required to induce labour were significantly less in the Propess group. Our data suggest that both Propess and Prostin are safe and effective in induction of labour, for either primips or multips. However, Prostin use is more cost-effective.", "Plasma levels of bicyclic PGE2 (PGE2M) were measured after administration of a 5mg, PGE2 slow release hydrogel pessary and a 3mg vaginal tablet (Upjohn). Twenty-four women of low parity with favourable induction features were randomised to receive either the hydrogel pessary or the vaginal tablet. A single pessary was administered and amniotomy was performed after 4 hours. Augmentation with oxytocin was carried out after amniotomy if required. Both groups showed a rise in plasma PGE2 levels in keeping with the release profiles of the pessaries. Wide interindividual differences in absorption were found.", "In a randomized study, uterine activity patterns were characterized with a portable pressure-sensitive device in 40 nonlaboring women at term with an unfavorable cervix who were undergoing preinduction cervical ripening with prostaglandin E2. The prostaglandin E2 was inserted into the posterior vaginal fornix as a single dose of either a 2.5 mg methylcellulose gel (20 cases) or 10 mg controlled-release pessary (20 cases). Uterine activity monitoring began 1 hour before dosing and continued for 12 hours. For those treated with the gel, low-amplitude, high-frequency contractions began within the first hour, reached a peak within 4 hours, and initiated sustained high-amplitude contractions in 10 (50%) cases. With the controlled-release pessary, low-amplitude, high-frequency contractions had a slightly later onset, reached a peak between the fifth and eighth hours, and initiated sustained high-amplitude contractions in 18 (80%) cases. Uterine hyperstimulation occurred in two (10%) pessary cases, with no adverse effect after removal. We conclude that low-amplitude, high-frequency uterine contractions began with either method of intravaginal prostaglandin E2 delivery but led to sustained, high-amplitude contractions primarily with the pessary.", "Induction of labour is a common obstetric intervention. When the cervix is unfavourable ripening agents are used, commonly prostaglandin E2. There are several methods of administration of prostaglandin E2 and little comparative work has been performed as to their acceptability by patients. Patients undergoing induction of labour by prostaglandin E2 were randomised to receive either intravaginal gel or an intravaginal slow-release pessary. Patient satisfaction with the method received was then assessed. Sixty-nine patients were randomised, 34 to receive gel and 35 to receive a pessary. Median scores for satisfaction of the induction process were the same for both methods; however, satisfaction with the labour was increased with those who had been randomised to the pessary group (median pessary=5, gel=4). There may be a marginal improvement in patient satisfaction when a slow-release intravaginal prostaglandin E2 pessary is used for the induction of labour.", "Prostaglandin E2 is effective for induction of labor but many preparations exist using a variety of vehicles from which the active ingredient may not be equally available. Plasma concentrations of bicyclic PGE2 metabolite (PGEM) and 13, 14-dihydro, 15-keto PGF2 alpha (PGFM) were measured following administration of a 3mg PGE2 vaginal tablet or 1mg PGE2 vaginal gel to twenty-four parous women with favorable induction features, randomly allocated to receive one or other preparation. PGEM increased rapidly following both administration of the 3mg PGE2 vaginal tablet and the 1mg PGE2 vaginal gel, reaching a peak within 40 minutes of PGE2 administration. The maximal rise in PGEM in the gel group correlated directly with the change in cervical score and inversely with the need for augmentation with oxytocin and the induction-delivery interval. A secondary rise in PGFM was noted in both groups 3-4 hours following PGE2 administration. The magnitude of the increase in PGE2 may be important in the clinical response to PGE2 administration, while PGE2 absorption may switch-on endogenous PGF2 alpha production, similar to what is seen in spontaneous labor.", "Fifty-four patients were randomized in a double blind fashion into either a placebo group or a group treated with a 3 mg dose of an intravaginal prostaglandin E2 gel. The group receiving the prostaglandin E2 gel had a mean change in cervical score of 2.7 while the patients in the placebo group had no significant change. Even though a significantly higher number of patients in the prostaglandin group went into spontaneous labor, the incidence of cesarean section was not different between the two groups. Upon comparing the conflicting reports of various studies on the subject, it is concluded that the method of product preparation, particularly the source of prostaglandin E2 utilized and the choice of drug vehicle, may be important variables in determining treatment success, as measured in terms of decreased cesarean section rate.", "A prospective randomized study of 267 pregnant women was undertaken to compare the efficacy of a pharmacy-prepared 3-mg prostaglandin E2 (PGE2) vaginal suppository with a 3-mg PGE2 vaginal tablet for induction of labor and cervical ripening. No statistically significant difference in success frequency was found between the two groups, either on the first day (72% and 74%, respectively; p greater than 0.05) or on the second day (89% in both groups). There was an equal proportion of women requiring oxytocin augmentation in the two groups, but the slower releasing properties of the vaginal tablet were reflected in a longer mean induction--delivery interval of about 4 h for this group. In both the pessary and the vaginal tablet groups, women who had not gone into labor on the first day showed a statistically significant increment in the Bishop score on the morning of the second day. The frequency of cesarean section was the same in both groups, but instrumental deliveries were more frequent in the vaginal tablet group. It is concluded that PGE2 vaginal tablets--a chemically stable alternative to pharmacy prepared pessaries--appear to be effective as regards cervical ripening as well as for labor induction.", "Slow release prostaglandin pessary (propess) is compared with instant release prostaglandin gel (prostin) for the induction of labour in nulliparous women with a modified Bishop's score of less than 6. In this randomised study 50 women received prostin gel and 45 received propess. More than one dose of prostaglandin was required to achieve amniotomy more often in the propess group (53%) compared with the prostin group (34%) (P=0.03). Propess was unable to demonstrate any advantage over Prostin gel group. Propess was not cost-effective in this study.", "This study represents the first of its kind in Kuwait. Two preparations of prostaglandin E2 (PGE2) have been compared as agents for induction of labor. In a randomized controlled study of 200 women of low parity and unfavorable cervical induction features induction of labor by means of a single vaginal tablets of PGE2 was compared with locally prepared PGE2 vaginal pessaries. The gradual increase of uterine contractions and the establishment of labor in a similar way to that observed during spontaneous labor was more apparent after PGE2 tablets. Labor induction was successful in 80% of patients in PGE2 tablet group compared with 59% in PGE2 pessaries group. The incidence of cesarean section was equal in both groups (4%), but none was performed due to uterine hyperactivity. The data presented indicate that the PGE2 vaginal tablet is safe and effective in induction of labor in healthy women at term.", "A group of 84 women at 39-43 weeks of pregnancy were randomly allocated to a blind trial of induction of labor with vaginal suppositories containing inert material or either 0.2 mg or 0.4 mg of prostaglandin E2. The suppositories were self-administered every two hours during waking hours on two successive days until labor started or 15 had been used. Side-effects were absent. Labor was established within 48 hr of insertion of the first suppository in 9.3% of control patients, 65.4% of those treated with 0.2 mg PGE2 and 85.7% of those treated with 0.4 mg PGE2. The mean Apgar scores in the three groups were the same. The mean total dose of PGE2 were 2.0 mg (0.2 mg group) and 2.3 mg (0.4 mg group). It is concluded that vaginal PGE2 is an effective and acceptable method of inducing labor at term.", "To compare conservative versus prostaglandin management of prelabour rupture of the membranes (PROM) in healthy primigravid women at term.\n A prospective randomized study.\n Labour Ward, Aberdeen Maternity Hospital.\n 230 primigravidae at terms with PROM, 115 allocated to be treated conservatively and 115 to be managed with prostaglandin treatment.\n In the conservatively managed group the women were observed for up to 24 h after hospital admission with PROM. The actively managed group had PGE2 gel (2 mg) instilled into the posterior fornix and if contractions had not commenced, a further dose of PGE2 gel (1 mg) was instilled 6 h later. In both groups, if labour had not established 24 h after admission, intravenous oxytocin was given in escalating doses.\n PROM to delivery interval, oxytocin augmentation, mode of delivery, maternal and neonatal infective morbidity.\n There was a significant reduction in the PROM to delivery interval in the women managed actively with PGE2 gel and fewer women in the PGE2 group required oxytocin augmentation (31% vs 51%). The two managements groups were comparable for intrapartum analgesia, antibiotic treatment, babies requiring admission to the special care nursery unit and delivery by caesarean section.\n The early use of prostaglandin is associated with a significant reduction in PROM to delivery interval without a significant increase in infective morbidity or caesarean section rate. However, the advantages of the conservative approach should not be overlooked. More work is still needed in the management of those women where uterine activity fails to establish within 24 h after PROM.", "Fifty nine women with prelabour rupture of membranes, unfavourable cervix and no evidence of infection or fetal distress were randomized formally to receive prostaglandin E2 (3mg) gel or sterile K-Y Jelly intravaginally. Conservative expectant management was followed for the next 24 hours. The subsequent management of the labour followed departmental protocol. The women who received prostaglandin went into labour sooner and were delivered earlier but the duration of labour was not significantly different. There were no significant differences in other clinical outcomes. There was 1 case of uterine rupture in the prostaglandin group. We conclude that early intervention with prostaglandin E2 gel intravaginally confers no advantage compared with conservative management except for earlier confinement in this group of patients.", "To compare the efficacy and safety of a prostaglandin E2 (PGE2) vaginal insert with PGE2 administered as a vaginal tablet.\n A randomized, observational study was performed. Women requiring induction of labor were randomly assigned to receive either a 10-mg PGE2 vaginal insert (group 1, n = 100) or 3-mg PGE2 tablets twice at six-hour intervals (group 2, n = 100). The primary efficacy outcome variable was vaginal delivery within 24 hours of insertion. The criteria for safety were the occurrence of uterine hyperstimulation, abnormal fetal heart rate patterns, use of beta 2-sympathomimetic drugs and fetal outcome.\n No differences in terms of vaginal delivery or cesarean section within 24 hours of induction were found. The cesarean section rate was 21% in group 1 and 22% in group 2. The interval from insertion of the induction agent to the onset of regular uterine contractions and the insertion-to-delivery interval were not different between the two cohorts. No difference in the frequency of uterine hyperstimulation, use of beta 2-sympathomimetic drugs, abnormal fetal heart rate patterns, fetal outcome, or oxytocin and analgesic requirements were found. In seven of eight patients in group 1 who experienced uterine hyperstimulation, removal of the insert was sufficient to stop it, whereas in group 2, of nine cases, eight needed medical interventions to end hyperstimulation (P = .003).\n The continuous release of PGE2 from the vaginal insert permits controlled induction of labor, and easy removal of the drug in cases of uterine hyperstimulation is possible.", "Tylose gel containing either 1.5 mg, 3.0 mg or 10.0 mg of prostaglandin F2 alpha was inserted into the posterior vaginal fornix of 165 patients on the evening before induction of labour. A control group of 100 patients received the gel alone. There was a significant reduction in the induction-delivery interval in nulliparae receiving at least 3.0 mg of prostaglandin, whereas, in multiparae all doses achieved this effect. There was also a significant reduction in the incidence of forceps delivery in nulliparae who received 3.0 mg or more of the prostaglandin gel; however, there was no difference in the incidence of spontneous labour, epidural anaesthesia or Caesarean section between the patients who received prostaglandin or those receiving gel alone.", "A randomised controlled trial was conducted to compare the clinical efficacy and cost-effectiveness of Dinoprostone Slow Release Pessary (Propess) with Gel (Prostin) for induction of labour (IOL) at term. A total of 120 women requiring IOL at term with no previous uterine surgery and no contraindication to prostaglandins were included. The main outcome measures were efficacy of drug preparations, patient satisfaction and the cost-effectiveness. The secondary outcome measures noted were maternal complications during the labour, type of delivery, the neonate's Apgar scores at birth and 5 min and incidence of significant morbidities. There were insignificant differences between the two groups in induction-to-delivery interval, mode of delivery, number of women delivering within 24 h and neonatal outcomes. However, the number of vaginal examinations was significantly lower in the Propess group. Propess was found to be more cost effective compared with Prostin in view of single dose and less midwifery hours.", "The efficacy of a vaginal gel containing either 5 mg prostaglandin E2 (PGE2) or 25 mg prostaglandin F2 alpha (PGF2 alpha) to ripen the unfavourable cervix for labour induction was assessed in a double blind trial. PGF2 alpha, compared with PGE2, had little effect upon the clinical state of the cervix, but the resultant duration of labour in each of the two groups was shorter than in a control group. While the numbers of patients requiring oxytocin stimulation of labour and regional analgesia were reduced in both groups compared with the controls, PGF2 alpha was much less effective than PGE2. Uterine hypertonus was observed using both prostaglandins during an experimental study and the implications are discussed.", "Our objective was to determine the best treatment for parturients at term with an unfavorable cervix and premature rupture of membranes (PROM).\n In this prospective study, 96 women with PROM and an unfavorable cervix were randomized into one of three treatment groups: oxytocin induction, vaginal prostaglandin E2 gel followed by oxytocin, or expectant management.\n Length of labor, cesarean section rate, and maternal/neonatal morbidity were not significantly different. In contrast, the interval from PROM until delivery and length of hospital stay were significantly longer in the expectantly managed group than in the other groups. Four of the patients who received expectant management required delivery because of nonreassuring fetal assessments.\n Expectant management of PROM at term significantly prolongs hospital stay without decreasing the incidence of abdominal delivery or infectious morbidity. There appears to be potential for cord compression in patients managed expectantly without continuous electronic fetal surveillance.", "Eighty patients with a Bishop score of less than or equal to 4 were randomly administered vaginal triacetin gel containing placebo or prostaglandin E2 in 1, 2, and 3 mg doses. Twelve to sixteen hours later, those not in labor underwent oxytocin induction. Increasing doses of prostaglandin were effective in ripening the cervix, and the higher doses were associated with significant success in inducing labor.", "Although there are many comparative studies concerning the local administration of prostaglandin E2 gel for cervical ripening and labor induction, the safety, efficacy and the appropriate route and dose of the gel are still debated.\n One hundred and ten women with high-risk pregnancy and unripe cervix received prostaglandin E2 gel 1 mg intravaginally (n=35), 2 mg intravaginally (n=36) and 0.5 mg intracervically (n=39), maximally three times at 6-hour intervals for cervical ripening prior to labor induction. The safety, efficacy and optimal dose were assessed.\n The 2 mg intravaginal gel and the 0.5 mg intracervical gel were equally effective and more effective than the 1 mg intravaginal gel in labor characteristics such as ripening time and cesarean section rate, but not in labor time. However, the failure rate (labor could not be induced) was highest in the intracervical group (10.3%) compared to the intravaginal groups (2.9% and 2.8%), although the differences were not statistically significant. In the two intravaginal groups three and five patients received the third gel application and one patient in both groups could not be induced. In the intracervical group the ripening of the cervix failed in all patients, who received the third gel. The neonatal outcome was uneventful in all groups. There were two cases of uterine hypertonus associated with fetal bradycardia, one in the intracervical and one in the 2 mg intravaginal group. Thus careful fetal monitoring is necessary. Furthermore, the vaginal route has the advantage of an easier technique of administration and obviously lower risk for inadvertent extraamnial instillation.\n We recommend the use of multiple applications of 2 mg intravaginal prostaglandin E2 gel as a safe, effective and easy method for preinduction cervical ripening in high-risk pregnancies. More than three gel applications hardly increase the efficacy." ]

[ "8165070", "2704497", "6988006", "12534029", "327364", "7375188", "8885917", "1536246", "7025638", "10488363", "7352521", "4011071", "15342900", "11530870", "2665800", "375171", "10329891" ]

[ "Prenatal dexamethasone treatment in conjunction with rescue therapy of human surfactant: a randomized placebo-controlled multicenter study.", "Use of ampicillin and corticosteroids in premature rupture of membranes: a randomized study.", "The influence of betamethasone and orciprenaline on the incidence of respiratory distress syndrome in the newborn after preterm labour.", "[Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study].", "Antenatal glucocorticoid therapy for the prevention of respiratory distress syndrome in the premature infant.", "Maternal glucocorticoid in unplanned premature labor. Controlled study on the effects of betamethasone phosphate on the phospholipids of the gastric aspirate and on the adrenal cortical function of the newborn infant.", "Preterm premature ruptured membranes: a randomized trial of steroids after treatment with antibiotics.", "A randomized, placebo-controlled trial of betamethasone for the prevention of respiratory distress syndrome at 24 to 28 weeks' gestation.", "Effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome.", "The use of dexamethasone in women with preterm premature rupture of membranes--a multicentre, double-blind, placebo-controlled, randomised trial. Dexiprom Study Group.", "Results of a double-blind controlled study on the use of betamethasone in the prevention of respiratory distress syndrome.", "Premature rupture of membranes: a prospective, randomized evaluation of steroids, latent phase, and expectant management.", "Blood pressure at 6 years of age after prenatal exposure to betamethasone: follow-up results of a randomized, controlled trial.", "The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes.", "Antenatal administration of betamethasone to prevent respiratory distress syndrome in preterm infants: report of a UK multicentre trial.", "Risk of respiratory distress syndrome after prenatal dexamethasone treatment.", "Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia." ]

[ "A placebo-controlled, randomized, double-blind study was performed to determine whether prenatal dexamethasone (DEX) treatment improves the outcome of the preterm infant when exogenous surfactant is available.\n 157 pregnant women at five hospitals with threatened preterm delivery and with lengths of gestation < 32 weeks received either DEX (dose 6 mg four times at 12-hour intervals) or placebo (PL). Prenatal treatment was not repeated. Preterm infants received rescue therapy of human surfactant (maximum four doses) if they required ventilatory support and at least 40% oxygen for the treatment of respiratory distress syndrome (RDS).\n Enrolled pregnant women delivered 188 live-born neonates, of whom 79 (DEX 41 and PL 38 neonates) were born 1 to 14 days after the prenatal treatment. Neonates born within 1 to 14 days after the initial DEX treatment had a lower incidence of RDS (DEX, 44%; PL, 79%; P < .01), lower requirements of surfactant (DEX, 22%; PL, 53%; P < .01), shorter duration of ventilatory support (DEX, 2.0 days; PL, 5.3 days; P < .05) and oxygen therapy (DEX, 2.0 days; PL, 7.0 days; P < .01), and a higher neonatal survival without ventilatory support (P < .05) than PL-treated neonates. DEX-treated neonates had higher mean blood pressure than PL-treated neonates during the first 3 days after birth. Among all neonates treated with DEX, there was a lower incidence of intraventricular hemorrhage or periventricular leucomalacia (DEX, 13%; PL, 33%; P < .01). Reduction in the incidence of intraventricular hemorrhage or periventricular leucomalacia in DEX-treated neonates was particularly associated with exogenous human surfactant therapy (DEX+surfactant 10%; PL+surfactant 48%; P < .01).\n Prenatal DEX treatment combined with exogenous human surfactant therapy in preterm infants decreases pulmonary morbidity and cerebral complications, and increases survival without severe morbidity.", "A randomized study was conducted to investigate the effects of antenatal corticosteroids and ampicillin in the management of preterm pregnancies under 34 weeks complicated by premature rupture of membranes. Patients with documented lecithin/sphingomyelin (L/S) ratios of less than 2.0 and a singleton gestation were eligible to participate in the study. One hundred sixty-five patients qualified and were randomized, using sealed envelopes, to four study groups. All patients were followed expectantly. Group I (41 patients) received neither ampicillin nor corticosteroids. Group II (43 patients) received 24 mg of antenatal betamethasone. Group III (37 patients) received 2 g of intravenous ampicillin every 6 hours, with discontinuation of antibiotic therapy if cultures were negative for pathogenic bacteria. Group IV (44 patients) received both corticosteroids and ampicillin as described for groups II and III, respectively. Compared with patients not receiving corticosteroids, those administered antenatal corticosteroids experienced a reduction in the incidences of respiratory distress syndrome (53 versus 26%), bronchopulmonary dysplasia (23 versus 9%), severe grades of intracranial hemorrhage (15 versus 3%), and patent ductus arteriosus (18 versus 6%), with no difference in the incidence of maternal or neonatal infection. Compared with patients not receiving antenatal antibiotics, the group of patients treated with ampicillin on admission had a lower incidence of clinical chorioamnionitis (4 versus 26%) and neonatal sepsis (5 versus 10%). This reduction in infectious morbidity by antenatal ampicillin was restricted to those patients (28.4% of the study population) colonized with group B streptococci.(ABSTRACT TRUNCATED AT 250 WORDS)", "In a randomized double-blind trial on antenatal corticosteroid treatment for the prevention of respiratory distress syndrome (RDS) a corticosteroid related beneficial effect was found. Possibly of more significance was the finding that the children born within 12 hours of their mother's admission to hospital showed a higher incidence of RDS than those born between 12 hours and one week after admission even in the placebo and untreated groups. Bèta-adrenergic drugs seemed to exert no other influence on the occurrence of RDS than can be explained by the delay of delivery. Prolonged ruptured membranes appeared to decrease the incidence of RDS to the same extent as other symptoms of threatened preterm labour.", "The aim of the study was to determine the feasibility, the cost and the effects of antenatal maternal corticosteroid treatment on preventing respiratory distress syndrome in premature neonates of our population.\n Between January, 1, 1998 and June, 31, 1999, 118 pregnant women at 26-34 weeks' gestation and at a high risk of premature delivery, were prospectively randomized in 2 groups: group 1 received intramusculary 24 mg of betamethasone (12 mg every 24 hours), group 2 didn't receive antenatal corticosteroids. At birth, premature neonates were systematically examined by a neonatologist.\n 131 premature neonates were born (63 from group 1, 68 from group 2). The incidence and the degree of severity of respiratory distress syndrome, appeared substancially reduced (4.8% vs 27.9%) by the use of antenatal corticosteroids. Moreover, neonatal mortality due to respiratory distress syndrome was statistically less in group 1 than in group 2 (22.9% vs 57%). There was no significant difference in the occurrence of maternal or neonatal corticosteroid complications such as infection between treated group and control subjects. We estimated a potential annual savings of 21 thousands tunisian dinars, when the cost implications for antenatal corticosteroid therapy were estimated to 2 thousands tunisian dinars.\n Maternal administration of corticosteroids before preterm delivery results in a decrease in the incidence and severity of respiratory distress syndrome and a decrease in neonatal mortality rate among premature neonates born to treated versus untreated mothers at 26-34 weeks' gestation; added to an annual savings estimated to 21 thousands tunisian dinars.", "A double-blind study was designed to investigate the effects of antenatal glucocorticoids on the incidence of respiratory distress syndrome (RDS) in 128 premature human infants. There was a significant reduction (P less than 0.05) in the incidence of RDS in the betamethasone-treated infants to 8.7% compared to an incidence of 22.6% in the saline-treated controls and 25.0% in infants whose mothers received methylprednisolone. The effectiveness of betamethasone in reducing RDS was limited to premature infants delivered to mothers with intact fetal membranes and with an initial L/S ratio less than 2.0. The time between administration of the glucocorticoid and delivery did not significantly affect the incidence of RDS in this study. The failure of methylprednisolone to reduce the development of RDS in premature infants suggests its potential use in maternal therapy during pregnancy with minimal effects on fetal maturation.", "The effects of betamethasone on surfactant composition and neonatal adrenal function were compared with placebo in a double-blind study, which included 74 patients at risk for premature delivery. The overall incidence of respiratory distress syndrome was low, and no differnce was observed between the betamethasone and placebo groups. The phospholipid pattern (lecithin/sphingomyellin ratio, acetone precipitated lecithin, phosphatidylinositol/sphingomyelin ratio, and phosphatidylglycerol/sphingomyelin ratio) from gastric aspirates of newborn infants was similar in the betamethasone and placebo groups, suggesting a similarity in lung surfactant. The responsiveness of the adrenal cortex of the newborn infants, evaluated by a 2-hr adrenocorticotropic hormone test at the age of 24 hr, did not differ between infants whose mothers had received either betamethasone or placebo. The low incidence of respiratory distress syndrome in the betamethasone and placebo groups was ascribed in part to a high incidence of prolonged rupture of fetal membranes. Our results do not exclude the possibility that antenatal maternal administration of betamethasone could prevent respiratory distress syndrome in other defined high-risk infants.", "To assess the effectiveness of corticosteroids in patients with preterm premature rupture of membranes (PROM) after treatment with a broad-spectrum antibiotic, ampicillin-sulbactam.\n A randomized clinical trial of corticosteroids in patients with preterm PROM was undertaken after treating these patients for a minimum of 12 hours with ampicillin-sulbactam. No digital vaginal examinations were performed on these patients. Antibiotics were continued for 7 days and the steroids were repeated weekly. No tocolytics were used. The primary outcome measure was the incidence of respiratory distress syndrome (RDS). Secondary outcome measures included latency period and neonatal and maternal infectious morbidity.\n Seventy-seven patients were enrolled and data about their pregnancies were analyzed. No statistically significant difference in latency period was noted (14.7 days in the steroid group, 15.8 days in the no-steroid group). Both neonatal and maternal infectious morbidity were similar. A significant reduction in the incidence of RDS (18.4 versus 43.6%, P = .03) were observed in the steroid group.\n These data suggest that treating preterm PROM patients with a broad-spectrum antibiotic before corticosteroids decreases RDS without apparent adverse sequelae.", "Previous randomized controlled studies of corticosteroids for the reduction of respiratory distress syndrome have failed to demonstrate benefit in very early premature gestational age groups. A randomized, double-blind, placebo-controlled clinical trial of betamethasone given to mothers with intact membranes and threatened premature delivery between 24 and 28 weeks of pregnancy was conducted. Thirty-six patients were randomized to receive betamethasone, two doses of 12 mg, 24 hours apart, and 41 received placebo. No difference was found in the overall incidence of respiratory distress syndrome between the two groups (betamethasone vs placebo 0.55 vs 0.66) or in the incidence of respiratory distress syndrome in babies delivered between 1 and 7 days after the first dose of drug (betamethasone vs placebo 0.78 vs 0.88). Nor were there any differences observed in any measure of severity of respiratory distress syndrome between the groups. The neonatal death rates were also similar (betamethasone vs placebo 0.25 vs 0.24). The only difference seen was an unexpected reduction in the betamethasone group in the incidence of grades 3 and 4 intraventricular hemorrhage (betamethasone vs placebo 1/31 vs 9/36, p = 0.01). Therefore this study was unable to demonstrate any beneficial effect of corticosteroids in reducing respiratory distress syndrome at less than 28 weeks' gestation in spite of a sample size that had an 80% likelihood of detecting a 50% reduction in the incidence of respiratory distress syndrome with p = 0.05, which is the minimum reduction seen in virtually all randomized trials in other gestational age groups.", "A double-blind, collaborative, randomized trial was initiated in 1976 to evaluate dexamethasone administered to mothers as a method of preventing neonatal respiratory distress syndrome (RDS). Five centers enrolled 696 women at risk for premature delivery. Up to 20 mg of dexamethasone phosphate (5 mg every 12 hours) or a placebo was administered intramuscularly. The overall incidence of RDS was different between control subjects (18.0%) and steroid-treating mothers (12.6%) (P less than 0.05). The effect was, however, mainly attributable to discernible differences among singleton female infants (P less than 0.001), whereas no treatment effect was observed in male infants (P = 0.96). Non-Caucasians were improved whereas Caucasians showed little benefit. Fetal and neonatal mortality and maternal postpartum infection rates were not different. Neurologic examination at 40 weeks' gestation demonstrated no significant difference in the rate of abnormal outcomes in the neonatal steroid group (P = 0.2).", "To assess whether administration of dexamethasone in women with preterm premature rupture of membranes (PPROM) has an effect on the prevalence of maternal sepsis, neonatal respiratory distress syndrome (RDS), perinatal mortality and neonatal sepsis in a developing country.\n Six public hospitals in South Africa that deal mainly with indigent women.\n A multicentre, double-blind, placebo-controlled, randomised trial was performed on women with PPROM and fetuses of 28-34 weeks' gestation or clinically estimated fetal weight between 1,000 and 2,000 g if the gestational age was unknown. Women were randomised to receive either dexamethasone 24 mg intramuscularly or placebo in two divided doses 24 hours apart. All women received amoxycillin and metronidazole and were managed expectantly. Hexoprenaline was administered if contractions occurred within the first 24 hours after admission to the trial.\n The maternal outcome measures were clinical chorio-amnionitis and postpartum sepsis. The outcome measures for infants were perinatal death, RDS, mechanical ventilation, necrotising enterocolitis, and neonatal infection within 72 hours.\n One hundred and two women who delivered 105 babies were randomised to the dexamethasone group and 102 women who delivered 103 babies, to the placebo group. The groups were well balanced with regard to clinical features. There was a trend towards fewer perinatal deaths in the dexamethasone group: 4 compared with 10 (P = 0.16, odds ratio 0.37, 95% confidence intervals 0.09-1.34). A subanalysis of mothers who delivered more than 24 hours after admission to the study and their infants revealed a significant reduction in perinatal deaths; 1 death in the dexamethasone group and 7 in the placebo group, P = 0.047 (Fisher's exact test). No woman in either group developed severe sepsis, and the incidence of sepsis in the women did not differ significantly. Eleven infants in each group developed sepsis.\n This is the first randomised trial in women with PPROM to compare the effects of the use of corticosteroids with placebo, where all women received prophylactic antibiotics concomitantly with the corticosteroids. A trend towards an improved perinatal outcome was demonstrated in the women who received dexamethasone. There was no increased risk of infection in the women or their infants where dexamethasone was administered. Administration of corticosteroids to women with PPROM has more advantages than disadvantages in developing countries.", "A double-blind controlled study on the prenatal use of betamethasone in the prevention of respiratory distress syndrome (RDS) was carried out on 137 patients from 24 to 34 weeks' gestation. The incidence of RDS was less in the treated group (5%) than in control group (17%). The neonatal mortality rate was lower in the treated group (5%) than in the control group (18%) due to an excess of neonatal deaths in the placebo group.", "A prospective, randomized study was conducted comparing the use of betamethasone and early delivery, early delivery alone, and expectant management in patients in the 28th to 34th week of pregnancy with premature rupture of the membranes (PROM). Tocolytic drugs were used to delay delivery until 24 hours had elapsed after the first dose of steroid or 24 to 48 hours of latent period had elapsed in the second group. There were no significant differences in maternal age, gestation at PROM, maximum maternal temperature, birth weights, maternal hospital days, respiratory distress, maternal sepsis, or delivery routes in the three groups. Comparisons with one other similar prospective, randomized study support the concept that expectant management offers less risk from tocolytic side effects.", "To determine whether prenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome (RDS) alters blood pressure in childhood.\n Prospective follow-up study of a randomized, double-blind, placebo-controlled trial.\n National Women's Hospital (Auckland, New Zealand).\n Two hundred twenty-three 6-year-old children of mothers who presented with unplanned premature labor and took part in a randomized, controlled trial of prenatal betamethasone therapy for the prevention of neonatal RDS.\n Mothers received 2 doses of betamethasone (12 mg) or placebo, administered through intramuscular injection, 24 hours apart.\n Systolic and diastolic blood pressure at 6 years of age.\n Children exposed prenatally to betamethasone (n = 121) did not differ in systolic or diastolic blood pressure from children exposed to placebo (n = 102) (mean difference: systolic: -1.6 mm Hg; 95% confidence interval: -4.1 to 0.8 mm Hg; diastolic: -0.3 mm Hg; 95% confidence interval: -2.5 to 1.8 mm Hg).\n Prenatal exposure to betamethasone for prevention of neonatal RDS does not alter blood pressure at 6 years of age.", "This study was carried out to examine the effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes (PROMs). For this purpose, 139 patients with a singleton pregnancy (27-34 weeks of gestation) complicated by PROMs were evaluated prospectively during the period January 1997 to February 1999 at two Jordanian military hospitals (Prince Rhashed and Prince Zaid). Patients were allocated into two groups; Group 1 included 72 patients treated with dexamethsone (24 mg divided into 4 doses 12 hours apart), and Group 2 which included 67 patients whoreceived no treatment (control group). All women were examined clinically and the diagnosis of PROMs was demonstrated using vaginal speculum, nitrazine paper examination and ultrasonography. All neonates were evaluated clinically, radiologically, and by laboratory investigations. Pearson's Chi-square and Fisher's exact tests were used to assess the significance of differences between the two study groups. Respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular haemorrhage (IVH), and days of hospital stay were significantly reduced in premature infants of the corticosteroid treated women compared with the controls (p<0.04, p<0.04, p<0.04, and p<0.05, respectively). The perinatal mortality was significantly decreased among the corticosteroid treated group in the gestational subgroups 31-32 and 33-34 weeks (p<0.04), and in all birth weight subgroups (p<0.03). RDS was statistically a significant factor which resulted in increased perinatal mortality in the control group (p=0.02). Regarding the occurrence of postpartum endometritis there was a statistically significant increase among the corticosteroid treated group compared with the controls (p<0.04). Conclusion: Antenatal corticosteroid therapy in pregnancies complicated by PROMs has a positive influencing effect on premature infants between 31 and 34 weeks of gestation, decreasing significantly the perinatal morbidity and mortality. It should be used with particular relevance to the developing world where surfactant is not available or where neonatal intensive care units are lacking.", "In a prospective, randomized, double-blind, multicentre trial the effect of antenatal treatment with betamethasone phosphate was compared with placebo in the prevention of the respiratory distress syndrome (RDS) in preterm infants. The dose of betamethasone was 4 mg every 8 h for six doses, unless delivery occurred. The 251 women who were enrolled gave birth to 262 liveborn infants, 130 in the beta-methasone and 132 in the placebo group; the two groups were evenly matched in most respects. The diagnosis of RDS in the newborn was confirmed by two independent assessors. Seven of the 130 infants in the betamethasone group and 16 of the 132 in the placebo group developed RDS. In infants whose mothers had received at least three injections, RDS was also less frequent in the steroid group than in the placebo group (3/104 and 10/104 respectively; P less than 0.05). There was a significant reduction of RDS in those born between 24 h and 6 days after entry into the trial (0/30 and 8/45 respectively; P less than 0.05). The largest difference in frequency of RDS occurred in the subgroup of infants born before 34 weeks gestation, within 8 days of trial entry, and whose mothers had received at least three injections (0/27 steroid group and 7/32 placebo group; P = 0.03), and there were also significantly fewer neonatal deaths (2/27 and 13/32, respectively; P less than 0.01) in this subgroup. Betamethasone did not provoke earlier delivery. Premature rupture of the membranes and maternal hypertension did not seem to contraindicate the use of steroids: there was no increase in maternal or neonatal sepsis nor in stillbirth in hypertensive pregnancies in the steroid group. Neonatal jaundice was significantly less frequent in the steroid (55/129) than in the placebo group (81/127; P less than 0.01) but not in the subgroups born before 34 completed weeks gestation.", "A prospective double-blind randomized clinical trial was carried out to determine whether glucocorticoid treatment reduces the risk of respiratory distress syndrome (RDS) in prematurely born infants. There were 127 infants born to 122 mothers who received either steroid (dexamethasone phosphate) or placebo. No differences between groups occurred in risk factors for RDS (eg, prepartum asphyxia, male sex, cesarean section). When those who received a full course of dexamethasone therapy were compared with those who received placebo, a significant reduction was found in risk, severity, and deaths due to RDS. An increased incidence of infection in mothers treated with steroid was evident, particularly after premature rupture of membranes. We conclude that steroids are effective in reducing risk of RDS, but safer and more efficacious approaches for the prevention of RDS should be sought.", "The objective of the study was to determine the efficacy and side effects of corticosteroid therapy for pregnant women with severe preeclampsia in the prevention of respiratory distress syndrome in their premature neonates.\n A prospective double-blind randomized trial enrolled 218 pregnant women with severe preeclampsia and gestational age between 26 and 34 weeks. One hundred ten received betamethasone (12 mg administered intramuscularly, repeated after 24 hours and then once a week) and 108 received placebo. Relative risks and 95% confidence intervals of respiratory distress syndrome and other neonatal and maternal complications were calculated for corticosteroid use.\n Frequency of respiratory distress syndrome was significantly reduced in the corticosteroid group (23%) with respect to the placebo group (43%), with a relative risk of 0.53 (95% confidence interval 0.35-0. 82). Relative risks of intraventricular hemorrhage, patent ductus arteriosus, and perinatal infection were significantly decreased in the corticosteroid group: 0.35 (95% confidence interval 0.15-0.86), 0.27 (95% confidence interval 0.08-0.95), and 0.39 (95% confidence interval 0.39-0.97), respectively. There was no significant difference in the frequency of stillbirth, but the neonatal mortality rate was lower in the corticosteroid group (14%) than in the placebo group (28%), with a relative risk of 0.5 (95% confidence interval 0.28-0.89). There was increased risk of gestational diabetes but of no other maternal complication after corticosteroid therapy, and mean blood pressures were similar in the 2 groups.\n Antenatal corticosteroid therapy with betamethasone for acceleration of fetal lung maturity is a safe and efficient treatment in patients with severe preeclampsia at between 26 and 34 weeks' gestation." ]

[ "3616531", "11115000", "7703876", "2285437", "15270928", "9024115", "1250282", "16150265" ]

[ "Early and late discharge after hospital birth. A comparative study of parental background characteristics.", "Does the duration of postnatal stay influence breast-feeding rates at one month in women giving birth for the first time? A randomized control trial.", "Postpartum early discharge: impact on maternal fatigue and functional ability.", "A randomized, controlled evaluation of early postpartum hospital discharge.", "Home-based versus hospital-based postnatal care: a randomised trial.", "A randomized trial of a program of early postpartum discharge with nurse visitation.", "Perinatal care of low-risk mothers and infants. Early discharge with home care.", "Early discharge from obstetrics-pediatrics at the Hospital de Valme, with domiciliary follow-up." ]

[ "When an early postnatal discharge program was introduced in Falun, Sweden in 1984, with early discharge defined as discharge 24-48 hours after birth combined with home visits on the following days, an investigation into background characteristics of parents choosing to participate and not to participate in the evaluative study of the program was initiated. 164 participants were compared with 354 non-participants. Data were collected mainly from questionnaires, 8 weeks before term. The participants were a more heterogeneous group than was expected when starting the program. Compared with the non-participants, they were characterized by: a less positive attitude to post-partum care in hospital and greater self-confidence in terms of confidence when thinking of birth and parenthood. They were more often multipara and had experienced rather less complicated pregnancies. They were a little younger and somewhat less well educated as a group, but the proportion of well educated women was the same as among non-participants. They had attended antenatal classes this pregnancy to a lesser extent, but felt better prepared for the delivery. They had a greater number of supportive persons available in case of early discharge. There was no difference between participants and non-participants as regards economy, housing conditions, distance to hospital, proportion of immigrants, paternal interest in childbirth and parenthood, equality in parental relations, social contacts, and leisure activities.", "The aim of the study reported in this paper was to examine the effect of postnatal stay on breast-feeding rates at one month using a randomized control trial. Participants were recruited during parent-craft classes at a large teaching hospital in the north of England. Nulliparous women in the last trimester of pregnancy were randomly allocated to a short hospital postnatal stay (6-48 hours), or a longer stay (more than 48 hours). The mothers were contacted at one month following the birth to ask about the method of feeding. The study was approved by the hospital ethical committee, and participation was voluntary. The results demonstrated no significant effect of postnatal stay on breast-feeding rates at one month. The main limitation of the study was the reluctance of the mothers in the long stay group to stay in hospital for longer than three days. This resulted in only a small difference between the lengths of hospital stay of the two interventions. The overall breast-feeding rate for the study group had increased significantly when compared with local city wide rates. This increase may be as a result of a sampling bias or a Hawthorne effect.", "The purpose of this study was to determine the impact of a postpartum early discharge program, with home follow-up by hospital nursing staff, on the maternal fatigue and functional ability of low-risk mothers with healthy neonates. A quasi-experimental design was used. Subjects were randomly assigned to one of two groups receiving the early-discharge program (hospital stay less than 60 hours plus home follow-up by hospital-based nurses; n = 35) or traditional hospital care (hospital stay more than 60 hours and no home follow-up by hospital staff; n = 17). A third group emerged from those originally assigned to traditional care but later transferred to early discharge due to bed shortages (n = 29). The Rhoten Fatigue Scale and the Inventory of Functional Status After Childbirth were used to collect the data at discharge and 1 and 6 weeks postpartum period. No significant differences between groups were found, suggesting that early discharge with adequate home follow-up does not affect the low-risk mother's fatigue and functional ability to any significantly greater extent than traditional care. It was also noted that, regardless of type of care, the proportion of subjects reporting severe fatigue was relatively large (25%, 31%, and 19% at discharge, 1 and 6 weeks postpartum period), highlighting the need for further study of maternal fatigue in the postpartum period.", "At approximately 37 weeks' gestation, 131 women were randomly assigned to one of three postpartum hospital discharge times: 12 to 24 hours, 25 to 48 hours, and 4 days. Depending on group assignment, the women received from one to five home visits by a maternity nurse clinician during the first 10 days postpartum. The results indicated the maternal and infant morbidity were low regardless of discharge time, although sample sizes were too small to detect significant differences in the outcomes. More early discharge mothers were breastfeeding without supplement at 1 month than were mothers in the long stay group. Mothers in the two early discharge groups were significantly more satisfied with their care than were those who remained longer. Those hospitalized longer scored higher on measures of depression and lower on scores of confidence at selected time periods.", "To compare a shortened hospital stay with midwife visits at home to usual hospital care after delivery.\n Randomised controlled trial.\n Maternity unit of a Swiss teaching hospital.\n Four hundred and fifty-nine women with a single uncomplicated pregnancy at low risk of caesarean section.\n Women were randomised to either home-based (n= 228) or hospital-based postnatal care (n= 231). Home-based postnatal care consisted of early discharge from hospital (24 to 48 hours after delivery) and home visits by a midwife; women in the hospital-based care group were hospitalised for four to five days.\n Breastfeeding 28 days postpartum, women's views of their care and readmission to hospital.\n Women in the home-based care group had shorter hospital stays (65 vs 106 hours, P < 0.001) and more midwife visits (4.8 vs 1.7, P < 0.001) than women in the hospital-based care group. Prevalence of breastfeeding at 28 days was similar between the groups (90%vs 87%, P= 0.30), but women in the home-based care group reported fewer problems with breastfeeding and greater satisfaction with the help received. There were no differences in satisfaction with care, women's hospital readmissions, postnatal depression scores and health status scores. A higher percentage of neonates in the home-based care group were readmitted to hospital during the first six months (12%vs 4.8%, P= 0.004).\n In low risk pregnancies, early discharge from hospital and midwife visits at home after delivery is an acceptable alternative to a longer duration of care in hospital. Mothers' preferences and economic considerations should be taken into account when choosing a policy of postnatal care.", "Our purpose was to compare an early postpartum discharge program versus standard postpartum care.\n A randomized controlled trial in a 637-bed university hospital included 175 healthy women recruited at 32 to 38 weeks gestation from physicians' offices and sonograms. Experimental intervention consisted of discharge 6 to 36 hours post partum with nursing care available by telephone or at home at 34 to 38 weeks' gestation and at < or = 48 hours and at 3, 5, and 10 days post partum. The control included a postpartum stay of 48 to 72 hours and standard follow-up.\n At 1 month no significant differences were seen in perceived maternal competence (Experimental-Control = 4.3 points [95% confidence interval-7.7 to 16.3]), infant weight gain (1.2 gm/ day [-2.8 to 5.2]); identification of significant neonatal hyperbilirubinemia (rate ratio 0.50 [0.10 to 2.51]), infant utilization of health services (rate ratio 0.88 [0.45 to 1.73]), or predominant breast-feeding (adjusted odds ratio 1.25 [0.88 to 1.75]). Program participants did have significantly less frequent infant bilirubin testing (rate ratio 0.39 [0.17 to 0.94]). The program also enhanced perceived maternal competence in recent immigrants (26.9 points [2.7 to 51.5]).\n Early postpartum discharge coupled with prenatal, postnatal, and home contacts leads to no apparent disadvantage and may yield benefits for some mothers and infants.", "A family-centered perinatal-care program featuring collaboration by nurse practitioners, obstetricians, pediatricians, and paramedical personnel was developed to enhance family participation and achieve a shorter but safe hospital stay. Discharge from the hospital was permitted as early as 12 hours after delivery. A perinatal nurse practitioner made daily home visits. The program's safety, feasibility, and acceptability to patients was studied by comparison of 44 patients so treated (study group) with 44 receiving traditional care (controls). Twenty-one study families, but no controls, went home within 24 hours. The study and control groups had no significant differences or trends in numbers of types of morbidity during hospitalization or the six-week post-partum period. The expense of the program is approximately equaled by hospital costs saved through early discharge. The results indicate that early discharge with home-care follow-up observation as described is safe, economically feasible, and well accepted by patients.", "This study was undertaken to evaluate the advantages and disadvantages of a program of early obstetric-pediatric discharge (24 hours postpartum) with domiciliary follow-up, compared with the traditional postpartum hospital stay (more than 48 hours), according to the criteria described by reviewers of the subject.\n A randomized controlled trial of early obstetric discharge for healthy mothers and term infants, with postpartum randomization, with no prenatal preparation and with observational and clinical follow-up was performed. The participants were mothers with healthy, term neonates (37-42 weeks) weighing more than 2500 g and produced via vaginal delivery and with a verified normal evolution before discharge. The sample consisted of 430 cases (213 cases with early discharge, and 217 control cases) in which the following variables were evaluated: existence of complications in the mother and/or child that required rehospitalization or a medical consultation, existence of maternal problems of fatigue or anxiety/depression after the birth, continuity of lactation and its problems, satisfaction of the mother and family, and relative costs.\n After demonstrating the homogeneity of the groups, no significant differences were found in the rates of maternal rehospitalization (1.9% in the early discharge group vs 2.3% in the control group, relative risk 0.81, 95% CI 0.21-3.03) or in the rates of rehospitalization of the neonates (1.4% in the early discharge group vs 2.3% in the control group, relative risk 0.16, 95% CI 0.15-2.56). No increases were observed in maternal or neonatal disease, puerperal fatigue, or maternal anxiety/depression. A prolongation of maternal lactation to 3 months was observed in the early discharge group (P=.016 <.05 Fisher exact test). When the cost of early discharge is compared with that of traditional discharge with a minimum of 48 hours hospital stay, we find a saving of 18% to 20%. The level of maternal satisfaction with early discharge is better than 90%." ]

[ "3907580", "3310952", "2873131", "6151958", "2858187", "3310018", "6138925", "2948987", "7480531", "2861873", "2690163", "6139353", "3058290", "21897464", "8195582", "2759809", "3542981" ]

[ "Alprazolam vs amitriptyline in depressions with reduced REM latencies.", "Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression.", "Comparative efficacy of alprazolam, imipramine, and placebo administered once a day in treating depressed patients.", "Double-blind clinical study comparing alprazolam and doxepin in primary unipolar depression.", "Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression.", "A double-blind comparative study of alprazolam and dothiepin hydrochloride in the treatment of anxiety associated with depression.", "A double-blind comparison of alprazolam vs. imipramine and placebo in the treatment of major depressive disorder.", "Alprazolam versus imipramine in depressed out-patients with neurovegetative signs.", "Treatment of depressive outpatients with lorazepam, alprazolam, amytriptyline and placebo.", "An evaluation of alprazolam in the treatment of reactive or neurotic (secondary) depression.", "Double-blind comparison of 3- and 6-mg fixed doses of alprazolam vs. placebo in outpatients with major depressive disorder.", "Alprazolam and amitryptyline: a double blind comparison of anxiolytic and anti-depressant activity.", "A comparison of the efficacy and safety of alprazolam and desipramine in depressed outpatients.", "A double-blind evaluation of alprazolam and imipramine in the treatment of major depression.", "Alprazolam and amitriptyline in the treatment of moderate depression.", "A comparison of alprazolam with amitriptyline in the treatment of patients with neurotic or reactive depression. A report of a randomised, double blind study by a General Practitioner Working Party.", "Comparison of alprazolam and imipramine for treatment of outpatient depression." ]

[ "This study was designed to compare the antidepressant effects of alprazolam, a triazolobenzodiazepine, with amitriptyline hydrochloride in a group of patients with nonpsychotic, major depressions diagnosed by Research Diagnostic Criteria. A mean rapid eye movement latency of less than 65 minutes was required to enter this study. Dexamethasone suppression tests were conducted before treatment. By strictly applied Research Diagnostic Criteria, 83.6% of the subjects were endogenous, and 34.7% were inpatients. A significantly greater percentage of alprazolam-treated patients responded within the first seven days of treatment. By the end of this six-week trial, alprazolam was associated with significant reductions in Hamilton, Beck, Covi, Raskin, and Carroll Rating scores (pretreatment to posttreatment). However, by the end of treatment the effects of amitriptyline exceeded those of alprazolam on both the Hamilton and Beck scales. These data indicate that alprazolam is not as effective as amitriptyline in major depressions with a shortened rapid eye movement latency.", "Two hundred forty-one outpatients with a DSM-III diagnosis of major depressive disorder participated in a six-week double-blind therapeutic trial of alprazolam, diazepam, imipramine hydrochloride, and placebo. Side effects were given as a major reason for attrition by patients taking the three active compounds and ineffectiveness was the reason given by patients taking placebo. Imipramine-treated patients reported the most and placebo patients the least number of adverse effects. Imipramine and alprazolam, but not diazepam, produced significantly more improvement in depressed symptomatology than did placebo. Mean diazepam scores frequently assumed an intermediate position between those of imipramine or alprazolam and placebo. These treatment differences were found to be independent of initial severity levels of anxiety and depression.", "Ninety-eight outpatients with major depressive disorder were treated with alprazolam, imipramine, or placebo in a 6-week, double-blind study. Average doses were 3.67 mg of alprazolam and 167 mg of imipramine, given at bedtime. Fifty percent of patients taking alprazolam, 38.2% taking imipramine, and 17.7% receiving placebo improved their HAM-D scores by more than 50%. Eight patients on imipramine, 6 on alprazolam, and 1 on placebo dropped out because of side effects. The most common side effects for imipramine were tachycardia, constipation, light-headedness, and sedation; common side effects of alprazolam were light-headedness, sedation, and unsteadiness.", "The therapeutic effect and safety of alprazolam and doxepin were studied in 126 outpatients suffering from primary unipolar depression. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with a flexible dose of 1.0-4.5 mg of alprazolam and 50-225 mg of doxepin per day. The mean final doses were 2.7 mg for alprazolam and 137.5 mg for doxepin. The results indicate that alprazolam and doxepin were equally efficacious. The incidence of side-effects was lower in the alprazolam treatment group.", "Five hundred four outpatients suffering from a major depressive episode were randomly assigned to receive either amitriptyline, doxepin, alprazolam, or placebo. The study was conducted in three treatment centers during a six-week period. All three active medications produced significantly more clinical improvement than did placebo, irrespective of the patient's initial anxiety, depression, and psychomotor retardation and irrespective of the patient's assignment to various subtypes of depression, including the DSM-III melancholia subtype. Compared with placebo, sedation was reported more frequently with all three medications, whereas anticholinergic effects were reported more frequently only for the two tricyclic antidepressants, but not for alprazolam.", "One hundred patients with mixed symptoms of anxiety and depression were enrolled into a prospective, multi-centre, randomized, double-blind study comparing the response to, and the side-effects of, alprazolam and dothiepin hydrochloride over 4 weeks of treatment. Mean daily doses were 2.33 mg alprazolam and 115 mg dothiepin. Data on 96 patients were evaluated for tolerance, and data for 85 patients were analyzed for therapeutic response. In each case, the groups were similar in numbers, mean ages and sex ratios. Both groups experienced satisfactory responses to therapy, with highly statistically significant changes (p less than 0.001) in the means of all efficacy measures within each group. No statistical difference was demonstrated in favour of either treatment group. Both dothiepin and alprazolam exhibited a similar profile of mild minor side-effects, but more patients suffered moderate to severe reactions to dothiepin, leading to a greater drop-out rate in the dothiepin-treated group. It is concluded that, as both treatments produced equally satisfactory responses in this study, alprazolam should be considered for the treatment of anxiety associated with depression in patients for whom tricyclic antidepressant drugs are either contra-indicated or poorly tolerated.", "In a 6-week double-blind trial 129 outpatients with major depressive disorder received either alprazolam, imipramine or placebo. Dosage was adjustable from 0.5 mg alprazolam, 25 mg imipramine or two capsules placebo b.i.d. to 4.5 mg alprazolam, 225 mg imipramine or three capsules placebo t.i.d. Both active drugs were more effective than placebo according to all the rating scales used. Alprazolam and imipramine did not differ consistently except in the somatic symptom cluster on the Hamilton Anxiety Rating Scale. Mean final daily dosage was 2.7 mg alprazolam, 117.3 mg imipramine and 7.2 capsules placebo. Patients on alprazolam reported fewer side effects than patients on imipramine and approximately the same number as patients on placebo. Anticholinergic side effects were commonly associated with imipramine; drowsiness was the most frequent side effect with alprazolam.", "The purpose of this study was to compare the safety and efficacy of a relatively new antidepressant drug, alprazolam (a triazolobenzodiazepine) with imipramine in the treatment of 60 depressed symptomatic volunteers. Eligible patients were randomly assigned after a 1-week washout to one of the medications and followed for 6 treatment weeks. Contrary to the earlier report of Feighner et al. (1983), who found alprazolam superior to imipramine and placebo, but consistent with Rush et al. (1985) we find imipramine superior in efficacy to alprazolam on a variety of symptoms. Both the present study and Rush's study employed patients with signs indicative of response to tricyclics. Feighner's patients may have been the type who tend to be less responsive to tricyclics but may be more responsive to alprazolam. Some of our data also show that alprazolam may have a more advantageous effect in the early weeks of treatment but is overtaken in subsequent treatment weeks by imipramine.", "This randomized double-blind study in 342 mildly to moderately depressive outpatients investigated the antidepressant effectiveness and speed of action of lorazepam, alprazolam and amitriptyline versus placebo. Six weeks of drug treatment were followed by a drug taper period, a control period with placebo and a control period without placebo, of 2 weeks duration each. Clinical improvement was assessed by rating scales (Clinical Global Impressions, Hamilton Rating Scales for Depression and Anxiety) and patient's self-ratings (Patient's Global Impressions, Self-rating Depression Scale and Visual Analogue Scale). At the end of week 6 all active drugs showed similar efficacy which was significantly superior to placebo. Compared to placebo, onset of efficacy was earlier on benzodiazepines than on amitriptyline . While tapering by decreasing the dosage, replacing drug with placebo and finally discontinuing placebo, clear withdrawal phenomena were not seen, but 20% of patients, equally distributed to all treatment groups, did not want to stop taking tablets after replacing drug with placebo. Drop-out rate during the treatment period was very low (9%). Significantly interfering adverse effects were seen in 27 patients, without predominance in one of the active drug groups.", "To investigate the effectiveness of a new benzodiazepine, alprazolam, and to compare this with amitriptyline (AMT) and with placebo, a trial was undertaken in 65 patients in whom depression was considered to be the dominating feature but not considered to be the primary cause of their condition; it was designed to exclude endogenous depressions. A consistent pattern was found favouring alprazolam over AMT both in rate of response and in total response, as well as significant differences in favour of both alprazolam and AMT over placebo. A comparison of side effects showed a definite trend in favour of alprazolam and placebo over AMT.", "nan", "nan", "Fifty-two adult depressed outpatients fulfilling Research Diagnostic Criteria for Definite Major Depressive Disorder were enrolled in a double-blind study comparing the antidepressant effects of alprazolam versus desipramine. Twenty-nine patients completed the seven week (one week placebo followed by six weeks of active drug) study. The mean daily dose of alprazolam and desipramine at study termination was 3.34 mg and 192 mg respectively. Based on psychometric ratings of depression (Hamilton Scale) and severity of illness (Clinical Global Impressions) there was no significant difference between alprazolam and desipramine at the end of six weeks of active drug treatment. Both medications were well tolerated with drowsiness being the most common side effect of alprazolam, and insomnia, dry mouth, and constipation, the complaints most associated with desipramine.", "This report describes the results of a multicentre collaborative study comparing the safety and efficacy of alprazolam with imipramine in patients suffering from major depressive disorder. Two hundred and eight patients diagnosed as major depression as per DSM-III criteria were randomly allocated to alprazolam (N= 105) or imipramine (N = 103) in a double-blind fashion. Detailed assessments were carried out for a period of six weeks. Results revealed that alprazolam was as effective as imipramine as an antidepressant. Side effects were less frequently reported with alprazolam.", "Forty-three out-patients with depression of a moderate degree were enrolled in a randomized, double-blind parallel group study comparing amitriptyline and alprazolam for 6 weeks of treatment. Patients were evaluated at the end of placebo washout and at Weeks 1, 2, 3 and 6 of drug therapy using the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory (BDI) and Clinical Global Impression (CGI). Drug dosage was determined in a fixed-flexible design resulting in mean final doses of alprazolam 3.2 mg/day and of amitriptyline 115 mg/day. Although both drug groups improved there were statistically significant differences in favour of amitriptyline at the end of the study on the HAM-D, BDI and HAM-A scales. Patients on amitriptyline reported more side effects overall than patients taking alprazolam with significantly more reports of dry mouth in the amitriptyline group.", "104 patients suffering from neurotic or reactive depression were treated with either alprazolam or amitriptyline in randomised, double-blind fashion. Seventeen patients were either lost to follow-up or withdrawn before week 2 (13 due to side effects and 1 because she was feeling better). A further 7 patients did not comply with the protocol, giving a total of 24 patients whose data were not considered suitable for inclusion in the analysis of therapeutic assessments. Evaluation of the 80 patients (40 in each group) who completed at least 2 weeks of the 4-week study demonstrate that both treatments produced a statistically significant response rate. There was a more rapid effect in those patients who received amitriptyline, but there was no significant difference in response between the treatment groups after 4 weeks treatment. Analysis of safety and side effect data on 101 patients (50 treated with alprazolam and 51 with amitriptyline) shows no statistically significant difference in the overall number of side effects experienced in each group, although 11 of those patients who received amitriptyline withdrew because of adverse reactions before completing the study compared to 6 in the alprazolam group. These results suggest that alprazolam may be a useful treatment for patients with neurotic or reactive depression not requiring hospitalisation.", "A 6-week double-blind comparison of the therapeutic efficacy of alprazolam and imipramine in 90 depressed psychiatric outpatients revealed a significantly superior response to alprazolam in the first 2 weeks of treatment as measured by total scores on the Hamilton Rating Scale for Depression and the Brief Psychiatric Rating Scale. Further analyses revealed that all significant differences could be accounted for by the superior effect of alprazolam on sleep disturbance. By the end of Weeks 4 and 6, no significant differences in therapeutic response between the two treatment groups were noted, with patients in both groups evidencing improvement on all measures. A differentially high dropout rate among patients in the imipramine treatment group posed a problem for interpretation of results in the latter weeks of treatment." ]

[ "12014724", "12390096", "16393297", "15354280", "16020489", "15667494", "15000272", "11564007", "12692051", "16128674" ]

[ "Safety and tolerability of tegaserod in patients with irritable bowel syndrome and diarrhea symptoms.", "A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation.", "Effect of a laxative with and without tegaserod in adolescents with constipation predominant irritable bowel syndrome.", "Effect of tegaserod in chronic constipation: a randomized, double-blind, controlled trial.", "A randomised controlled trial assessing the efficacy and safety of repeated tegaserod therapy in women with irritable bowel syndrome with constipation.", "Tegaserod for the treatment of chronic constipation: a randomized, double-blind, placebo-controlled multinational study.", "A double-blind, placebo-controlled, randomized study to evaluate the efficacy, safety and tolerability of tegaserod in patients with irritable bowel syndrome.", "Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation.", "An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome.", "Effect of tegaserod on work and daily activity in irritable bowel syndrome with constipation." ]

[ "Tegaserod is a selective serotonin (5-HT4) receptor partial agonist effective in providing relief from abdominal pain, bloating, and constipation in patients with irritable bowel syndrome. Tegaserod therapy may be associated with early transient diarrhea, which is related to its mechanism of action. This study was performed in patients with irritable bowel syndrome and symptoms of diarrhea to further assess the safety of tegaserod.\n After a 2-wk baseline, patients were randomized (2:2:1) in a double-blind manner to receive 4 mg of tegaserod a day (n = 35), 12 mg of tegaserod a day (n = 34), or placebos (n = 17) for 8 wk. Patients had to fulfill > or =2 Rome diarrhea criteria > or =25% of the time. Adverse events were recorded.\n Diarrhea, abdominal pain, headache, flatulence, and fatigue were the most frequently reported adverse events. The frequency rates of diarrhea were 49%, 18%, and 35% for the 4 mg/day, 12 mg/day, and placebo groups, respectively; when the tegaserod data were pooled, the frequency of diarrhea was similar to that of the placebo group (33% and 35%, respectively). No complications of diarrhea (e.g., dehydration and electrolyte abnormalities) were reported. Five patients (6%), all from the tegaserod groups, discontinued study participation because of diarrhea and/or abdominal pain. No serious adverse events were reported.\n In this study, tegaserod at doses of 4 and 12 mg/day was safe and not associated with complications of diarrhea or serious adverse events.", "Irritable bowel syndrome is a common functional gastrointestinal disorder which affects up to 20% of the population, with a predominance in females.\n To evaluate the efficacy and safety of tegaserod in female patients with irritable bowel syndrome characterized by symptoms of abdominal pain/discomfort and constipation.\n In a randomized, double-blind, multicentre study, 1519 women received either tegaserod, 6 mg b.d. (n = 767), or placebo (n = 752) for 12 weeks, preceded by a 4-week baseline period without treatment and followed by a 4-week open withdrawal period. The primary efficacy evaluation was the patient's symptomatic response as measured by the Subject's Global Assessment of Relief. Other efficacy variables included abdominal pain/discomfort, bowel habits and bloating.\n Tegaserod produced significant (P < 0.05) improvements in the Subject's Global Assessment of Relief and other efficacy variables. These improvements were seen within the first week, and were maintained throughout the treatment period. After withdrawal of treatment, the symptoms rapidly returned. Overall, tegaserod was well tolerated. Diarrhoea was the most frequent adverse event; however, this led to discontinuation in only 1.6% of tegaserod-treated patients.\n Tegaserod, 6 mg b.d., produced rapid and sustained improvement of symptoms in female irritable bowel syndrome patients and was well tolerated.", "To determine the effect of a laxative alone and in combination with tegaserod in alleviating pain and improving stool frequency in adolescents with constipation predominant irritable bowel syndrome.\n Forty-eight postpubertal adolescents of both sexes with constipation predominant irritable bowel syndrome, as defined by Rome II criteria, were randomly allocated to Group A (n = 27) for treatment with a laxative (polyethylene glycol 3350 oral solution) only or Group B (n = 21) for combination therapy with the laxative and tegaserod. Symptoms of abdominal pain (scale 0-10) and frequency of bowel movements were recorded daily in the pre-treatment phase and the post-treatment phase after a 7-day 'washout' period. Patients served as their own controls.\n Treatment with the laxative alone (Group A) resulted in significant increase in frequency of bowel movements (P < 0.05), but not significant improvement in pain (P > 0.05). Treatment with the combination of the laxative and tegaserod (Group B) led to significant increase in the frequency of bowel movements and also significant reduction in pain (P < 0.05).\n The laxative alone improved stooling but not pain in adolescents with constipation predominant irritable bowel syndrome. Addition of tegaserod resulted in alleviation of pain as well.", "Chronic constipation is a common gastrointestinal disorder. The aim of this study was to evaluate the efficacy, safety, and tolerability of tegaserod, a serotonin subtype 4 receptor partial agonist in patients with chronic constipation.\n This was a randomized, double-blind, placebo-controlled study. After a 2-week baseline, patients received tegaserod 2 mg twice daily (n = 450), tegaserod 6 mg twice daily (n = 451), or placebo (n = 447) for 12 weeks, followed by a 4-week withdrawal period. Responders were those patients having been treated for at least 7 days with an increase of > or =1 complete spontaneous bowel movement/week vs. baseline during weeks 1-4 (primary variable) and weeks 1-12 (secondary variable). Other secondary variables included patient assessment of constipation symptoms (number of bowel movements, stool form, abdominal bloating/distention, straining, and abdominal pain/discomfort), and global assessment of constipation and bowel habits.\n Responder rates for complete spontaneous bowel movement during weeks 1-4 were significantly greater ( P < 0.0001) in the tegaserod 2 mg twice daily (41.4%) and 6 mg twice daily groups (43.2%) vs. placebo (25.1%). This effect was maintained over 12 weeks. Statistically significant improvements over placebo were observed across the majority of secondary variables for both tegaserod doses. No rebound effect was observed after treatment withdrawal. Tegaserod was well tolerated; headache and nasopharyngitis, the most frequent adverse events, were more common in the placebo group than in either tegaserod group.\n Over 12 weeks, tegaserod treatment produced significant improvements in chronic constipation symptoms and was also safe and well tolerated.", "It has been proposed that treatments for irritable bowel syndrome with constipation (IBS-C) should provide rapid symptomatic relief, be intermittent, and effective upon repeated use.\n To evaluate the efficacy and safety of tegaserod on IBS symptoms, and its impact on quality of life and health economic measures.\n Women (> or = 18 years of age) with IBS-C according to the Rome II criteria.\n Prospective, double blind, placebo controlled, randomised trial. Women with IBS-C either received tegaserod 6 mg twice daily or placebo for one month. Patients with at least a partial response entered a treatment free interval. Upon symptom recurrence, tegaserod treated patients were re-randomised to tegaserod or placebo for an additional month. Primary efficacy variables were response (overall IBS symptoms and abdominal discomfort/pain) to first and repeated treatment. Analysis was by intention to treat.\n 2660 patients and 1191 patients were randomised for first and repeated treatment respectively. Tegaserod was superior to placebo for each primary efficacy variable (first treatment: 33.7% v 24.2% responders respectively for relief of IBS symptoms and 31.3% v 22.1% for relief of abdominal discomfort/pain; repeated treatment: 44.9% v 28.7%, and 42.4% v 27.1%, all p < 0.0001). Tegaserod was superior to placebo for every secondary efficacy variable (relief of abdominal discomfort/pain, bloating and constipation; stool frequency and consistency). A response to tegaserod was observed within the first treatment week. Tegaserod produced greater satisfaction, work productivity, and improved quality of life than placebo (p < 0.05).\n Tegaserod provides rapid and sustained relief of IBS-C symptoms both during first and repeated treatment.", "Chronic constipation is a common, persistent disorder with limited effective treatment options. This study investigated the efficacy, safety, and tolerability of tegaserod in the treatment of chronic constipation.\n After a 2-wk baseline period, patients were randomized to double-blind treatment of 12 wk with tegaserod (2 or 6 mg b.i.d.) or placebo. Response during weeks 1-4 (primary variable) was defined as an increase in complete spontaneous bowel movement (CSBM)/wk. Secondary variables included response during weeks 1-12, patient evaluation of individual symptoms, and global assessment of bowel habits and constipation.\n One thousand two hundred and sixty-four patients were randomized to tegaserod or placebo. Responder rates for the primary efficacy variable were 35.6% for tegaserod 2 mg b.i.d. (p= 0.0059 vs placebo), 40.2% for 6 mg b.i.d. (p < 0.0001 vs placebo) and 26.7% for placebo. The number needed to treat was 7.3 for the 6 mg b.i.d. dose compared with 11.1 for tegaserod 2 mg b.i.d. Tegaserod 6 mg b.i.d. reduced straining, abdominal bloating/distension, and abdominal pain/discomfort during the 12-wk treatment period compared with placebo (p < 0.05 for all symptoms). Significant improvements were also seen in stool form and in global assessment of bowel habits and constipation. The most common adverse events, headache and abdominal pain, were more frequent with placebo than with tegaserod.\n Tegaserod was efficacious in relieving symptoms of chronic constipation and was well tolerated.", "Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western and Asia-Pacific populations. This study evaluated the efficacy, safety and tolerability of tegaserod versus placebo in patients with IBS.\n Patients with IBS (excluding those whose primary bowel symptom was diarrhoea) were randomized to receive either tegaserod 6 mg b.i.d. (n = 327) or placebo (n = 320) for a 12-week double-blind treatment period. The primary efficacy variable (over weeks 1 to 4) was the response to the question: 'Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?' Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and the individual IBS symptoms.\n Overall satisfactory relief was greater in the tegaserod group than in the placebo group. Over weeks I to 4, the odds ratio was 1.54, that is, the odds of satisfactory relief were 54% higher in the tegaserod group than in the placebo group (95% confidence interval for odds ratio (CI) (1.14, 2.08), P = 0.0049). Over weeks 1 to 12, the odds ratio was 1.78, that is, the odds of satisfactory relief were 78% higher in the tegaserod group than in the placebo group (95% CI (1.35, 2.34), P < 0.0001). A statistically significant therapeutic gain over placebo was observed for the majority of weeks from week 1 to week 12 (except weeks I and 4), with a mean therapeutic gain of 7.3 and 10.6 percentage points over weeks 1-4 and weeks 1-12, respectively. Headache was the most commonly reported adverse event (8.0% tegaserod versus 4.7% placebo). Diarrhoea was reported by 9.2% of patients on tegaserod (1.3% on placebo) and led to discontinuation in 2.8% of tegaserod patients.\n Tegaserod 6 mg b.i.d. is an effective, safe and well-tolerated treatment in patients suffering from IBS without diarrhoea as primary bowel symptom.", "To investigate the efficacy and safety of tegaserod, a novel 5-HT(4) receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study.\n Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks.\n Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with tegaserod than placebo.\n Based upon the results of this study, tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.", "Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western populations. However, little information is available regarding the use of tegaserod in the Asia-Pacific population.\n To evaluate the efficacy, safety, and tolerability of tegaserod versus placebo in patients with IBS from the Asia-Pacific region.\n A total of 520 patients from the Asia-Pacific region with IBS, excluding those with diarrhoea predominant IBS.\n Patients were randomised to receive either tegaserod 6 mg twice daily (n=259) or placebo (n=261) for a 12 week treatment period. The primary efficacy variable (over weeks 1-4) was the response to the question: \"Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?\" Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and individual symptoms of IBS.\n The mean proportion of patients with overall satisfactory relief was greater in the tegaserod group than in the placebo group over weeks 1-4 (56% v 35%, respectively; p<0.0001) and weeks 1-12 (62% v 44%, respectively; p<0.0001). A clinically relevant effect was observed as early as week 1 and was maintained throughout the treatment period. Reductions in the number of days with at least moderate abdominal pain/discomfort, bloating, no bowel movements, and hard/lumpy stools were greater in the tegaserod group compared with the placebo group. Headache was the most commonly reported adverse event (12.0% tegaserod v 11.1% placebo). Diarrhoea led to discontinuation in 2.3% of tegaserod patients. Serious adverse events were infrequent (1.5% tegaserod v 3.4% placebo).\n Tegaserod 6 mg twice daily is an effective, safe, and well tolerated treatment for patients in the Asia-Pacific region suffering from IBS and whose main bowel symptom is not diarrhoea.", "Tegaserod is a promotility agent with proven efficacy and safety in patients with irritable bowel syndrome with constipation.\n To assess tegaserod's effect on work productivity and daily activity.\n Women, 18-65 years old and meeting Rome II criteria for irritable bowel syndrome with constipation, were randomized to a double-blind, placebo-controlled, multicentre study of tegaserod 6 mg b.d. or placebo. Productivity loss and daily activity impairment because of irritable bowel syndrome were measured with the Work Productivity and Activity Impairment questionnaire for irritable bowel syndrome, modified to exclude diarrhoea as a symptom. Assessments were made at baseline, weeks 2 and 4.\n A total of 2660 women were randomized and, of these, 1675 [tegaserod (n = 1363), placebo (n = 312)] were employed and completed Work Productivity and Activity Impairment for irritable bowel syndrome questionnaires. Compared with placebo, tegaserod significantly reduced work and daily activity impairment at weeks 2 and 4. Tegaserod reduced absenteeism by 2.6% (P = 0.004), presenteeism by 5.4% (P < 0.0001), overall work productivity loss by 6.3% (P < 0.0001), and activity impairment by 5.8% (P < 0.0001) at week 4 (vs. baseline). Assuming a 40-h workweek, tegaserod reduced work productivity loss by 2.5 h/week.\n Tegaserod significantly reduced work productivity loss and daily activity impairment at 2 weeks, and this benefit was maintained at 4 weeks." ]

[ "15479311", "15098169", "10598427", "10389558", "16557440", "7653809", "9014544", "9640123", "15845680", "11973192", "11075558", "7577281", "11505347", "12198052", "11771598" ]

[ "Manual versus target-controlled infusions of propofol.", "[Comparison between TCI-TIVA, manual TIVA and balanced anaesthesia for stereotactic biopsy of the brain].", "[Comparison of manual infusion of propofol and target-controlled infusion: effectiveness, safety and acceptability].", "Safety and efficacy of target controlled infusion (Diprifusor) vs manually controlled infusion of propofol for anaesthesia.", "[Comparison of a propofol-based anesthesia regimen using optimated-target-controlled-infusion (OTCI) and manually-controlled infusion (MCI) technique].", "Comparison of propofol administration techniques for sedation during monitored anesthesia care.", "Comparison of computer-controlled administration of propofol with two manually controlled infusion techniques.", "TCI compared with manually controlled infusion of propofol: a multicentre study.", "A comparison of target- and manually controlled infusion propofol and etomidate/desflurane anesthesia in elderly patients undergoing hip fracture surgery.", "Target-controlled versus manually-controlled infusion of propofol for direct laryngoscopy and bronchoscopy.", "[Effects of infusion methods of propofol on quality of sedation and ease of sedation control during gynecological laparotomy under spinal anesthesia].", "Manual compared with target-controlled infusion of propofol.", "Target-controlled infusion or manually controlled infusion of propofol in high-risk patients with severely reduced left ventricular function.", "Bispectral index in patients with target-controlled or manually-controlled infusion of propofol.", "Propofol anaesthesia via target controlled infusion or manually controlled infusion: effects on the bispectral index as a measure of anaesthetic depth." ]

[ "Target-controlled infusion systems have been shown to result in the administration of larger doses of propofol, which may result in delayed emergence and recovery from anaesthesia. The aim of this study was to investigate if this was due to a difference in the depth of hypnosis (using the bispectral index monitoring) between the manual and target controlled systems of administration. Fifty unpremedicated patients undergoing elective surgery were randomly allocated to have their anaesthesia maintained with manual or target-controlled propofol infusion schemes. In both groups, the rate of propofol administration was adjusted according to standard clinical criteria while bispectral index scores were recorded by an observer not involved in the delivery of anaesthesia. The total dose of propofol used was higher in the target controlled group (mean 9.9 [standard deviation 1.6] compared with 8.1 [1.0] mg.kg(-1).h(-1) in the manual group [p < 0.0001]). The times to emergence and recovery end-points were comparable between the two groups. The difference in the total dosage of propofol was mainly due to higher rate of propofol administration in the first 30 min in the target controlled infusion group. The bispectral index scores were lower in the target controlled group during this time, being significantly so over the first 15 min of anaesthesia. We conclude that propofol administration by a target controlled infusion system results in the administration of higher doses of propofol and lower bispectral index values mainly in the initial period of anaesthesia.", "Total intravenous anaesthesia (TIVA) is increasingly used in diagnostic surgery such as stereotactic biopsy of the brain. TIVA could lead to a faster recovery of cerebral function, which may lead to a better behavior and advantages in the postoperative management. The aim of this prospective, single-blind study was to compare the hemodynamics, the postoperative recovery period, the side-effects and the need for additional cardiovascular medication during and after the operation between the three study groups.\n After giving informed consent and approval by the ethical committee of our hospital, 51 patients (ASA I and II) undergoing stereotactic biopsy of a brain tumor were randomized to receive either propofol via the TCI-system (group 1: TCI-TIVA), propofol by a manual technique (group 2: MAN-TIVA) or methohexitone-sevoflurane (group 3: BAL-SEVO). Remifentanil was used as the analgetic component in all groups. Systolic and diastolic blood pressure, heart rate und transcutaneous oxygen saturation were noted before and after induction and before and after the end of anaesthesia. The time until return of complete orientation relative to person, location and time were measured. The patients' ranking of their satisfaction with the anaesthesia was questioned 60 min and 24 hours after the end of the procedure (VAS). Undesirable side-effects (i. e. PONV, shivering, pain, dysphoria, tiredness) were noted, whenever they occurred. The number of hemodynamic interventions by the anaesthesiologist was counted, and the total doses of remifentanil and propofol were quoted. Depth of anaesthesia was monitored by using a BIS-system, a range between 40 and 50 was thought to be adequate. Besides this, the total doses of remifentanil, propofol and sevoflurane were ruled out and the costs of the three regimens were ranked.\n Heart rate dropped markedly in all groups with a maximum in the TIVA-collective. Systolic and diastolic pressure also fell in the groups. In the SEVO-group, the difference was statistically significant only at the end of anaesthesia. After extubation, the three groups reached their hemodynamic starting-point with a slight overshoot in the SEVO-group. The number of required hemodynamic interventions was two (TCI-TIVA) vs. 7 (MAN-TIVA) vs. 8 (BAL-SEVO) in each group, respectively. The difference scarcely failed to get significance. The remifentanil requirements were similar between the collectives, group 1 needed more propofol per time than group 2. The number of side-effects was very little after the different regimens. There were no differences with regard to the other measured parameters between the groups. The use of TCI-TIVA was more expensive than manual TIVA (18,85 euro vs. 12,50 euro). Surprisingly, balanced anaesthesia using Sevoflurane was the most expensive method during the first hour, mainly due to the use of methohexitone as the induction agent (23,90 euro).\n Each of the three techniques compared in our study is suitable for anaesthesia in diagnostic neurosurgery. Since fast recovery of vigilance is important to justify the neurological outcome, none of the methods seems to be superior to the others. The hemodynamics were largely stable with a strong trend towards minor necessity for hemodynamic intervention in the TCI-TIVA group. This is also the best method from the subjective point of view of the anaesthesiologist due to the easy handling and the low number of interventions. The use of newer TCI-systems (e. g. fm-controller, Braun, Melsungen) not operating with special application syringes will cheapen TCI-TIVA.", "Diprifusor TCI is a newly developed target-controlled system for the infusion of propofol. Purpose of this study is to evaluate the acceptability, efficacy and safety of Diprifusor TCI in comparison with the manually controlled technique.\n This multicentre, randomised, parallel group study was carried out in 160 patients undergoing surgical procedures of 10 min to 4 h duration in 8 centres. In each centre 20 male or female patients, aged > or = 18 years, ASA I-III were randomised to treatment with either Diprifusor TCI (TCI group--80 patients) or manually controlled infusion (MI group--80 patients). Assessments included hemodynamics; adverse events, including accidents, actual or possible; recovery times; anesthetist ratings of quality of induction and maintenance, and of ease of control and use of technique. Ratings were summed up in a global quality score (study end-point).\n Induction doses were significantly lower (median values 1.4 vs 1.9 mg/kg) and maintenance infusion rate significantly higher (median values 10.2 vs 8.8 mg/kg/h) in the TCI group; anesthetists ratings obtained maximum scores in most patients of either group, but more frequently in the TCI group, with significant differences for ease of control (good 91.2% TCI vs 74.7% IM; adequate 8.8 vs 21.5%; poor 0 vs 3.8%), and of use of technique (good 91.2% TCI vs 60.8% IM; adequate 8.8 vs 39.2%); the global quality score showed a significant advantage for the TCI system (median value 12 vs 11).\n The TCI technique is effective and safe, and has a better acceptability than the manually controlled infusion technique.", "In this multi-centre, randomized trial, we compared the safety and efficacy of Diprifusor TCI with manually controlled infusion (MCI) of propofol for anaesthesia. With approval, 123 adult male and female patients were studied. Firstly, each investigator anaesthetized five patients to familiarize themselves with Diprifusor TCI. In Stage 2, 98 patients were randomized to receive propofol-based anaesthesia via TCI or MCI. Adjuvant drugs, airway management and monitoring were managed at the discretion of the anaesthetist. Results are presented as mean (SD). Induction times were significantly longer [67 (32) vs 54 (17)s] and induction doses were significantly lower [14 (5) vs 16 (4) ml] in the TCI vs the MCI group. Recovery times and total doses were not significantly different. There were statistically but not clinically significant differences in mean arterial blood pressure and heart rate. Quality of anaesthesia and ease of control of anaesthesia were similar. We conclude that Diprifusor TCI and MCI are similar in terms of safety and efficacy.", "Propofol anesthesia based on target-controlled-infusion (TCI) has been shown to be superior to a manually-controlled-infusion (MCI) technique. A new optimal-target-controlled-infusion (OTCI) technique enables an individual plasma-targeted adjustment by including the concentration in the effect-compartment. This study compared practicability and costs of the new system with a conventional MCI-based propofol anesthesia regimen.\n In a prospective study, 50 patients scheduled for elective surgery of nose or nasal sinuses were randomly enrolled to receive BIS-controlled anaesthesia (level: 40-55) using either OTCI (n = 25) or MCI (n = 25). Hemodynamics, extubation times and time of awaking, rate and quality of propofol adjustment, total drug requirements, costs, postanaesthetic care unit (PACU) stay, Aldrete and pain scores, and adverse effects (postoperative nausea and vomiting (PONV), shivering) were recorded.\n Demographics, hemodynamics, and perioperative data including extubation times were comparable for both study groups. Propofol consumption was similar within the first 60 min for both groups, thereafter, significantly less propofol in the OTCI group (5.03 mg/kg/h) than the MCI group (5.79 mg/kg/h) was used. Costs for propofol was significantly reduced with OTCI (0.2 vs. 0.23 Cent/anaesthesia minute/kg), the administration of other anaesthetics (fentanyl, remifentanil, cis-atracurium) did not differ between the groups. The number of infusion adjustments to BIS values were not significantly different.\n The new OTCI-system is a safe and easily controllable technique. The obvious advantage of this infusion system appears to be a reduction in propofol consumption and direct drug costs for anaesthesia lasting longer than 60 min.", "Sixty-three outpatients undergoing breast biopsy procedures with local anesthesia were randomly assigned to receive propofol by intermittent bolus injections (n = 21), a conventional syringe infusion pump (n = 21), or a target-controlled infusion (TCI) device (n = 21) for intraoperative sedation. In the first two groups, an initial intravenous (IV) bolus of propofol (0.3 mg/kg) was administered and an attempt was made to maintain the sedation level at an Observer's Assessment of Alertness/Sedation (OAA/S) score of 3 or 4 with either intermittent bolus injections of propofol (10 mg) or a variable-rate infusion (25-100 micrograms.kg-1.min-1). In the TCI group, the initial target concentration of propofol was set at 2 micrograms/mL and the target concentration was adjusted between 1 and 4 micrograms/mL in an attempt to maintain an OAA/S score of 3 or 4. Recovery was assessed using clinical criteria, visual analog scales (VAS), and the digit-symbol substitution test (DSST). The overall quality of sedation, operating conditions, and clinical recovery profiles were similar in all three treatment groups. The anesthesiologist had to intervene more frequently in the intermittent bolus injection group than in the two infusion groups. We conclude that the use of an infusion technique may allow the anesthesiologist more time for monitoring the patient by decreasing the number of interventions necessary to administer supplemental doses of the sedative medication during the operation. However, the cost of the IV drug delivery system may become an increasingly important factor in the future.", "Ninety women were studied in order to compare dose requirements and quality of anaesthesia between target-controlled infusion and two manually controlled infusion schemes for propofol administration: group I received target-controlled infusion for induction (4 micrograms.ml-1 target blood concentration, increased by 2 micrograms.ml-1 after 3 min of consciousness not lost), groups II and III received an induction bolus of propofol at infusion rates of 1200 or 600 ml.h-1, respectively, until loss of consciousness. Anaesthesia was maintained with propofol target-controlled infusion in group 1 or by constant rate infusion in the other two groups. Computer simulations were used to calculate blood and effect-site propofol concentrations. Mean induction times (SD) were 78 (65)s in group I versus 51 (10)s and 62 (12)s in groups II and III, respectively (p < 0.05 between groups II and III). Mean induction doses were: 1.31 (0.44), 2.74 (0.56) and 1.77 (0.43) mg.kg-1 and mean maintenance doses were 13.4 (3.55), 9.32 (1.72) and 9.97 (1.53) mg.kg-1 h-1 in groups I, II and III, respectively (p < 0.05 between all groups). There was a lower incidence of apnoea in group I than in groups II and III. There were no significant differences between the groups in other objective parameters of anaesthetic quality studied. Computer simulations showed an \"overshoot' in propofol blood and effect-site concentration with manual induction and significantly higher maintenance levels with target-controlled infusion.", "This prospective, randomised multicentre study was designed to determine the clinical profile of 'Diprifusor' target controlled infusion compared with manually controlled infusion of propofol in 562 patients, aged 18-85 years, in a range of surgical procedures in 29 centres. The dose of propofol required for loss of consciousness was statistically significantly lower in the target controlled infusion group [1.69 (0.50) vs. 2.31 (0.75) mg.kg-1, p < 0.001] but the overall rate of propofol administration was slightly, but significantly, higher [12.1 (5.1) vs. 11.0 (6.0) mg.kg-1.h-1, p < 0.05]. The target concentration (CT) required for induction decreased with increasing age and ASA class, with premedication and with the administration of an opioid before induction. However, the amount of opioid given did not influence the CT required for induction, but enhanced the haemodynamic effects of propofol induction in both groups. Most investigators expressed an overall preference for target controlled infusion (93%) and found it easier to use (76%). Despite the lack of experience of most investigators in using target controlled infusion, the clinical profiles of both propofol administrations were similar. Data suggest that the clinical profile of target controlled infusion may be improved with experience, for example by more active titration of CT to effect. Target controlled infusion may well become the preferred choice for anaesthetists.", "Elderly patients have a higher risk of developing adverse drug reactions during anesthesia, especially anesthesia affecting cardiovascular performance. In this prospective randomized study we compared quality of induction, hemodynamics, and recovery in elderly patients scheduled for hip fracture surgery and receiving either etomidate/desflurane (ETO/DES) or target-controlled (TCI) or manually controlled (MAN) propofol infusion for anesthesia. Sixteen patients were anesthetized with ETO (0.4 mg/kg) followed by DES titrated from an initial end-tidal concentration of 2.5%. Eighteen patients received propofol TCI at an initial plasma concentration of 1 microg/mL and titrated upwards by 0.5-microg/mL steps. Fifteen patients received a bolus induction of propofol 1 mg/kg over 60 s followed by an infusion initially set at 5 mg . kg(-1) . h(-1). All received a bolus (20 microg/kg) followed by an infusion of 0.4 microg . kg(-1) . min(-1) alfentanil. According to hemodynamics, concentrations of DES or propofol (TCI group) and propofol infusion rate (MAN group) were respectively adjusted by a step of 20% and 50%. In the TCI and ETO/DES groups, the time spent at a mean arterial blood pressure within 15% and 30% of baseline values was more than 60% and 80% of anesthesia time, whereas in the MAN group it was <30% and 60%, respectively. In the MAN group more anesthetic drug adjustments were recorded (6.4 +/- 2.8 versus 2.5 +/- 1.2 [ETO/DES] and 2.6 +/- 1 [TCI]). TCI improves the time course of propofol's hemodynamic effects in elderly patients.", "Few studies have compared the clinical profile of target-controlled infusions of propofol with that of manually-controlled infusions. Fifty-four ASA physical status I or II patients scheduled for an elective otorhinolaryngology endoscopy performed under general anesthesia with spontaneous ventilation were enrolled in this prospective randomized study to compare the clinical outcome of such administrations. Before induction, all patients received a single alfentanil bolus dose (10 microg/kg). Propofol administration was adapted to maintain absence of movement, hemodynamic stability, and efficient spontaneous ventilation. When compared with the Manually-Controlled Infusion group, in the Target-Controlled Infusion group there were fewer movements at insertion of the laryngoscope (14.8% vs. 44.4%), improved hemodynamic stability (largest variations of mean arterial blood pressure <10% of control values, versus 20%), fewer episodes of apnea, and less respiratory acidosis after endoscopy (pH = 7.37 +/- 0.05 and PaCO(2) = 50 +/- 7 mm Hg versus pH = 7.28 +/- 0.06 and PaCO(2) = 58 +/- 9 mm Hg); the recovery was also shorter (time to opening eyes or verbal response, 4.6 +/- 2.0 min and 6.8 +/- 2.5 min versus 10.8 +/- 7.3 min and 15.7 +/- 7.1 min). Propofol consumption was comparable in the two groups. Targeting the effect-site concentration improved the time course of the propofol drug effect during direct laryngoscopy performed during spontaneous ventilation when compared with manual infusion.\n This study compares the clinical profile of propofol anesthesia for direct laryngoscopy with spontaneous ventilation when the drug is administered either as a manually controlled infusion or by targeting the effect-site concentration through a target-controlled infusion (TCI) device. TCI improves the time course of propofol effects.", "Twenty patients were prospectively and randomly studied to investigate effects of infusion methods of propofol on quality of sedation and ease of sedation control during gynecological laparotomy under spinal anesthesia. After establishment of spinal anesthesia, patients were randomly assigned to one of the following two groups, i.e. conventional continuous infusion group (Cont group) and target-controlled infusion group (TCI group). In the Cont group, propofol was started at a rate of 6 mg.kg-1.hr-1 until response to command disappeared. In the TCI group, the initial target concentration of propofol was set at 1.2 micrograms.ml-1 until response to command disappeared. Thereafter infusion rate or target concentration was adjusted to maintain Mackenzie's score at 3 or 4. Predicted concentration of propofol was 1.2 +/- 0.01 micrograms.ml-1 at induction of sedation and 1.2 +/- 0.11 micrograms.ml-1 during stable sedation in the TCI group. Satisfaction VAS, anxiety VAS, discomfort VAS, sedation score and times of changing infusion condition were similar in both groups. Total dose of propofol was significantly less in the TCI group. In conclusion, quality of sedation and ease of control of sedation were comparable in both groups and continuous infusion method is simple.", "We studied 160 ASA I-II patients, anaesthetized with propofol by infusion, using either a manually controlled or target-controlled infusion system. Patients were anaesthetized by eight consultant anaesthetists who had little or no previous experience of the use of propofol by infusion. In addition to propofol, patients received temazepam premedication, a single dose of fentanyl and 67% nitrous oxide in oxygen. Each consultant anaesthetized 10 patients in sequential fashion with each system. Use of the target-controlled infusion resulted in more rapid induction of anaesthesia and allowed earlier insertion of a laryngeal mask airway. There was a tendency towards less movement in response to the initial surgical stimulus and significantly less movement during the remainder of surgery. Significantly more propofol was administered during both induction and maintenance of anaesthesia with the target-controlled system. This was associated with significantly increased end-tidal carbon dioxide measurements during the middle period of maintenance only, but recovery from anaesthesia was not significantly prolonged in the target-controlled group. With the exception of a clinically insignificant difference in heart rate, haemodynamic variables were similar in the two groups. Six of the eight anaesthetists found the target-controlled system easier to use, and seven would use the target-controlled system in preference to a manually controlled infusion. Anaesthetists without prior experience of propofol infusion anaesthesia quickly became familiar with both manual and target-controlled techniques, and expressed a clear preference for the target-controlled system.", "To compare hemodynamics, time to extubation, and costs of target-controlled infusion (TCI) with manually controlled infusion (MCI) of propofol in high-risk cardiac surgery patients.\n Prospective, randomized.\n Major community university-affiliated hospital.\n Twenty patients undergoing first-time implantation of a cardioverter-defibrillator with severely reduced left ventricular function (left ventricular ejection fraction <30%).\n Anesthesia was performed using remifentanil, 0.2 to 0.3 microg/kg/min, and propofol. Propofol was used as TCI (plasma target concentration, 2 to 3 microg x mL; n = 10) or MCI (2.5 to 3.5 mg/kg/hr; n = 10).\n Hemodynamics were measured at 6 data points: T1, before anesthesia; T2, after intubation; T3, after skin incision; T4, after first defibrillation; T5, after third defibrillation; and T6, after extubation. There were no significant hemodynamic differences between the 2 groups. Dobutamine was required to maintain cardiac index >2 L/min/m(2) in significantly more patients of the TCI group than of the MCI group. Mean dose of propofol was higher in the TCI patients (6.0 +/- 1.0 mg/kg/hr) than in the MCI patients (3.0 +/- 0.4 mg/kg/hr) (p < 0.05), whereas doses of remifentanil did not differ. Time to extubation was significantly shorter in the MCI (11.9 +/- 2.4 min) versus the TCI group (15.6 +/- 6.8 min). Costs were significantly lower in MCI patients (34.73 dollars) than in TCI patients (44.76 dollars).\n In patients with severely reduced left ventricular function, TCI and MCI of propofol in combination with remifentanil showed similar hemodynamics. TCI patients needed inotropic support more often than MCI-treated patients. Although extubation time was longer in TCI patients and costs were higher, both anesthesia techniques can be recommended for early extubation after implantation of a cardioverter-defibrillator.\n Copyright 2001 by W.B. Saunders Company.", "In this prospective, randomized study we compared bispectral index (BIS), hemodynamics, time to extubation, and the costs of target-controlled infusion (TCI) and manually-controlled infusion (MCI) of propofol. Forty patients undergoing first-time implantation of a cardioverter-defibrillator were included. Anesthesia was performed with remifentanil (0.2-0.3 micro g. kg(-1). min(-1)) and propofol. Propofol was used as TCI (plasma target concentration, 2.5-3.5 micro g/mL; n = 20) or MCI (3.0-4.0 mg. kg(-1). h(-1); n = 20). BIS, heart rate, and arterial blood pressure were measured at six data points: T1, before anesthesia; T2, after intubation; T3, after skin incision; T4, after first defibrillation; T5, after third defibrillation; and T6, after extubation. There were no significant hemodynamic differences between the two groups. BIS was significantly lower at T3 and T4 in the TCI group than in the MCI group. The mean dose of propofol was larger in TCI patients (5.8 +/- 1.4 mg. kg(-1). h(-1)) than in the MCI patients (3.7 +/- 0.6 mg. kg(-1). h(-1)) (P < 0.05), whereas doses of remifentanil did not differ. Time to extubation did not differ between the two groups (TCI, 13.7 +/- 5.3 min; MCI, 12.3 +/- 3.5 min). One patient in the MCI group had signs of intraoperative awareness without explicit memory after first defibrillation (BIS before shock, 49; after shock, 83). Costs were significantly less in the MCI group (34.83 US dollars) than in the TCI group (39.73 US dollars). BIS failed to predict the adequacy of anesthesia for the next painful stimulus.\n In this prospective, randomized study, bispectral index (BIS), hemodynamics, time to extubation, and costs of target-controlled infusion (TCI) and manually-controlled infusion of propofol were compared. TCI increased the amount of propofol used. BIS failed to predict the adequacy of anesthesia for the next painful stimulus.", "Target controlled infusions (TCI) of propofol allow anaesthetists to target constant blood concentrations and respond promptly to signs of inappropriate anaesthetic depth. Studies comparing propofol TCI with manually controlled infusion (MCI) reported similar control of anaesthesia, but did not use an objective measure of anaesthetic depth. We therefore tested whether the Bispectral Index (BIS), an electroencephalographic (EEG) variable, is more stable during propofol TCI or MCI. Forty patients received midazolam and fentanyl before induction and were randomized to TCI or MCI. Target propofol concentrations in the TCI group were 3 to 8 microg/ml. The MCI group received propofol bolus (approximately 2 mg/kg) and infusion (3 to 10 mg/kg/h). Neuromuscular blockade was achieved with rocuronium. Following endotracheal intubation, nitrous oxide (66%) in oxygen was delivered and propofol infusion and fentanyl boluses were titrated against clinical signs. Blood pressure, heart rate and EEG were recorded, although the anaesthetist was blind to BIS values. The ideal BIS for general anaesthesia was defined as 50. Performance error, absolute performance error, wobble and divergence of BIS, and maximum changes in blood pressure and heart rate were compared using two-sample t-tests or rank-sum tests where appropriate. There was no difference in absolute performance errors during maintenance of anaesthesia with propofol TCI or MCI (23 +/- 11% vs 23 +/- 9%; P=0.97). The two groups did not differ significantly in performance error, wobble, divergence on haemodynamic changes. We conclude that TCI and MCI result in similar depth of anaesthesia and haemodynamic stability when titrated against traditional clinical signs." ]

[ "2874221", "373642" ]

[ "Family therapy in the treatment of severe childhood asthma.", "Childhood asthma. A controlled trial of family psychotherapy." ]

[ "Eighteen children with severe, chronic bronchial asthma were randomly divided into two groups. The families in one group received family therapy while the others served as a control group in a controlled family therapy study. Later the control families were also offered therapy in a before-after therapy design. All children were followed for 3 1/2 yr. Asthma symptoms, functional impairment and the use of drug (from diaries) were rated in ten different ways during eight months before and eight months after the family therapy. Improvement in the clinically most important variable, i.e. general pediatric assessment, was greater in the children in the family therapy group compared to the control group (p less than 0.05) Twelve children who received family therapy showed significant improvement after treatment concerning general pediatric assessment (p less than 0.01), clinical grading (p less than 0.05), peak expiratory flow (p less than 0.05), days with functional impairment/yr (p less than 0.05), no. of doses of inhaled Beta-2-agonists/month (p less than 0.01) and nights when Beta-2-agonists were inhaled (p less than 0.05). The children who only received conventional medical treatment showed no significant change in asthma symptoms. We draw the conclusion that family therapy may represent a valuable therapeutic tool in the management of severe asthma.", "In an attempt to evaluate the effectiveness of family psychotherapy as an adjunct conventional treatment in childhood asthma, children with moderate to severe asthma were randomly allocated to a control group or to an experimental group; the latter group received 6 hours of family treatment during a 4-month period, and both groups had standard medical treatment. While there was no significant difference between the two groups on three parameters, the experimental group were significantly better in day-wheeze score and thoracic gas volume. These results suggest that family treatment in selected cases may have a place in the overall management of childhood asthma, and that more research with larger numbers of children is necessary." ]

[ "8040776", "9535242", "8350584", "9457607", "8040775" ]

[ "Prevention of central venous catheter-related coagulase-negative staphylococcal sepsis in neonates.", "Selective use of vancomycin to prevent coagulase-negative staphylococcal nosocomial bacteremia in high risk very low birth weight infants.", "[Preventive antibiotic administration for prevention of nosocomial septicemia in very small premature infants (VLBW infants)--preventive vancomycin administration against infections with coagulase negative streptococci--prevention of translocation with oral cefixime therapy in intestinal colonization with pathogenic gram-negative pathogens].", "Low-dose vancomycin prophylaxis reduces coagulase-negative staphylococcal bacteraemia in very low birthweight infants.", "Prevention of gram-positive sepsis in neonates weighing less than 1500 grams." ]

[ "A randomized, double-blind, controlled trial was conducted to determine whether vancomycin added to parenteral alimentation solution given via a central venous catheter would decrease the incidence of catheter-related coagulase-negative staphylococcal sepsis. Seventy infants with a central venous catheter (CVC) in place were randomly selected to receive total parenteral nutrition--either the standard solution or a solution containing 25 micrograms of vancomycin per milliliter. Catheter-related sepsis was defined as the isolation of the same bacterial species from specimens of both peripheral and CVC blood with the concentration of bacteria at least tenfold greater in the specimen obtained from the CVC. Specimens from the CVCs were cultured on removal of the catheters to determine colonization. The colonization of catheters by coagulase-negative staphylococci was reduced from 40% to 22% (p = 0.03) in the vancomycin group; catheter-related sepsis was reduced from 15% to no cases (p = 0.004). Fewer infants required CVC reinsertion in the vancomycin-treated group (p = 0.02), who also regained birth weight earlier (13.4 vs 17.1 days (p = 0.014)). Adverse effects of vancomycin infusion were not observed. We conclude that vancomycin added to the solution used for total parenteral nutrition effectively reduces catheter-related sepsis in the neonatal intensive care unit and offers other potential benefits such as the need for fewer catheters and earlier weight gain. However, we do not recommend widespread implementation of this technique until there are data regarding the emergence of vancomycin-resistant organisms.", "To determine whether vancomycin added to parental nutrition (PN) fluids could prevent nosocomial infections in very low birth weight newborns and which infants would benefit most from prophylaxis.\n Double blind, randomized controlled study. SETTING AND STUDY POPULATION: Very low birth weight infants receiving PN in a tertiary neonatal intensive care unit.\n Thirty-eight infants with and without central vascular catheters were randomized to receive no medication or 25 microg/ml vancomycin added to PN for the duration of the infant's PN requirements.\n The addition of 25 microg/ml vancomycin to PN prevented bacteremia in very low birth weight infants receiving PN. There was a significant reduction in the number of coagulase-negative staphylococcal (CONS) bacteremias (defined as isolation of the same organism from two positive blood cultures) during PN (5 vs. 0; P = 0.037) as well as the total number of bacteremias and fungemias (9 vs. 1; P = 0.036). The total number of hospital days (108 +/- 13 vs. 76 +/- 6; P = 0.039) were reduced in infants receiving vancomycin. Infants with birth weights of < 1000 g who received corticosteroids for treatment of chronic lung disease benefitted most from treatment. No vancomycin-resistant strains of CONS or enterococci were detected during the study period.\n Prophylactic treatment with vancomycin effectively prevented CONS bacteremia under the conditions of the study. Its use was most effective in infants with birth weights of <1000 g.", "VLBW-infants below 1500 g of birth weight have a quite high risk to acquire a nosocomial sepsis. 20-40% of all infants exhibit signs of nosocomial infection once during neonatal intensive care. The rate of infection is related to technique and amount of used invasive devices as to gestational age. Coagulase-negative staphylococci (CONS) and gram-negative organisms contribute most to these cases of sepsis. In a three phase study we tried to demonstrate the efficacy of different mechanisms to change the rate of nosocomial sepsis. During the first phase a strict hygienical protocol was enforced as isolation, care with sterile gloves and aseptic techniques in introducing and maintaining i.v. lines. In a second phase we started a randomized controlled study of prophylactic vancomycin (10 mg/kg/day in two doses). In a third phase we added an oral antibiotic regime with cefixime for all patients with positive cultures for gramnegative organisms under the hypothesis of translocation from the gut as the way of infection. During the first phase 23.7% of 76 patients enrolled acquired CONS-sepsis, 0.52% gramnegative sepsis. During the second phase (41 patients) 6 patients in the control group acquired CONS-sepsis, none in the vancomycin-group. The rate of gramnegative infections was not different (4 and 3 cases). During the third phase (vancomycin plus cefixime eventually in cases of positive stool cultures) no case of nosocomial sepsis occurred (35 patients, 11 positive cultures). The management used in phase 3 reduced the rate of nosocomial infections in VLBW-infants drastically.", "Very low birthweight (VLBW) infants undergoing neonatal intensive care are at risk of infection with coagulase-negative staphylococci (CONS). This study investigates the efficacy of twice daily, 1 h infusions of vancomycin (5 mg kg) in reducing CONS infection in VLBW infants receiving parenteral nutrition. Of 72 infants in the study, 37 were randomized to vancomycin and 35 to the control group. Clinical variables and mortality were similar in both groups. In the vancomycin group, 11 infants had one or more episodes of CONS bacteraemia compared with 17 in the control group. Two babies in the treatment group had more than one episode of CONS bacteraemia, compared with nine in the control group (P = 0.02). There were 13 episodes of CONS bacteraemia in the vancomycin group compared with 29 in the control group. When only positive blood-cultures associated with a rise in C-reactive protein were considered, there were six episodes of CONS bacteraemia in the vancomycin group compared with 18 in the control group. Similarly there were five infants with one or more CONS infections compared with 11 in controls and one with more than one episode compared with six in the control group (P = 0.05). Prophylaxis with intermittent low-dose vancomycin infusions may help reduce recurrent CONS bacteraemia in VLBW infants receiving parenteral nutrition.", "A prospective, randomized study to evaluate the effectiveness of a continuous low-dose vancomycin infusion to prevent nosocomial gram-positive bacteremia was initiated within the first 2 weeks of life in neonates weighing < 1500 gm. Seventy-one infants received constant infusion of vancomycin (25 micrograms/ml) mixed with their total parenteral nutrition solution; 70 infants served as control subjects. The groups were clinically similar in birth weight, estimated gestational age, and severity of illness. Administration of vancomycin was begun at a mean age of 5.4 +/- 2.9 days. Infants had mean serum vancomycin concentrations of 2.4 micrograms/ml, and received vancomycin for a mean of 11 +/- 7 days. No vancomycin-resistant organisms were detected in surveillance cultures during the 2-year study period. Twenty-four of seventy control infants, in comparison with 1 of 71 infants receiving vancomycin, had gram-positive bacteremia (p < 0.001). The addition of a low dose of vancomycin to alimentation fluids virtually eliminated the incidence of gram-positive bacteremia in an at-risk population of very low birth weight infants. However, the widespread use of vancomycin in total parenteral nutrition solution is not recommended until better data on the emergence of vancomycin-resistant organisms are available." ]

[ "12369047", "15264186", "15784639", "15365963", "1457695", "8678065", "12324914", "9568857", "10737167", "11879247", "11417951", "10795662", "9669432", "3312761", "8887291", "11522879", "11095657", "10737166", "8297564", "10363631" ]

[ "[Acute and chronic effects of standard hemodialysis and soft hemodiafiltration on interdialytic serum phosphate levels].", "Removal of the protein-bound solute p-cresol by convective transport: a randomized crossover study.", "Pre-dilution on-line haemofiltration vs low-flux haemodialysis: a randomized prospective study.", "Comparison between hemofiltration and hemodiafiltration in a long-term prospective cross-over study.", "Removal of beta 2-microglobulin by hemodialysis and hemofiltration: a four year follow up.", "A prospective comparison of bicarbonate dialysis, hemodiafiltration, and acetate-free biofiltration in the elderly.", "Effect of acetate-free biofiltration and bicarbonate hemodialysis on neutrophil activation.", "Acetate-free biofiltration versus bicarbonate haemodialysis in the treatment of patients with diabetic nephropathy: a cross-over multicentric study.", "On-line haemodiafiltration. Remarkable removal of beta2-microglobulin. Long-term clinical observations.", "Online hemodiafiltration versus acetate-free biofiltration: a prospective crossover study.", "Clinical improvement by increased frequency of on-line hemodialfiltration.", "The effect of hemodialysis and acetate-free biofiltration on anemia.", "Effect of acetate, bicarbonate dialysis, and acetate-free biofiltration on nitric oxide synthesis: implications for dialysis hypotension.", "Comparison of hemodialysis and hypertonic hemodiafiltration on cardiac function [corrected].", "Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters. The Italian Cooperative Dialysis Study Group.", "Effect of acetate-free biofiltration on the anaemia of haemodialysis patients: a prospective cross-over study.", "A comparison of on-line hemodiafiltration and high-flux hemodialysis: a prospective clinical study.", "On-line haemodiafiltration versus low-flux haemodialysis. A prospective randomized study.", "Cardiovascular response during hemodialysis and hemofiltration: thermal, membrane, and catecholamine influences.", "Improved cardiovascular variables during acetate free biofiltration." ]

[ "The dialytic management of hyper-phosphoremia, which is inadequate because of insufficient intra-dialytic removal of phosphate (P), is further limited by PDR-P, i.e. the significant increase in serum P levels during the early postdialytic period. Patients and methods. To investigate the effects of enhanced P removal by haemodiafiltration on the inter-dialytic phosphoremia, we studied 12 uremic patients that were switched, with cross-over randomised modality, to a single session of standard hemodialysis (HD) and hemodiafiltration (HDF) (Acute Study). Blood samples were obtained before the treatment, at the end (T0), after 30, 60, 90 and 120 minutes, and at 24, 48 and 68 hours. During both dialytic treatments the whole effluent dialysate was collected to evaluate the intradialytic removal of P. Thereafter, patients were randomised to receive either HD or HDF for three months, in the presence of constantly similar Kt/V, food intake and dose of phosphate binder (Chronic Study).\n Acute Study. Compared to HD, P removal in HDF was about 44% greater in the presence of identical predialytic P levels (6.0+/-0.2 and 5.9+/-0.4 mg/dl) and Kt/V (1.35+/-0.06 and 1.34+/-0.05); however, the inter-dialytic decline of serum P levels did not differ (-50+/-3% versus -42+/-3%, p=0.098). In HDF, PDR-P was faster (30 min versus 90 min) and better (at T120: +69+/-6% versus +31+/-4%, p<0.001). The higher P levels were maintained throughout the inter-dialytic period whereas Ca x P changed in parallel. Chronic Study. During the three months, pre-dialytic serum P diminished in HDF (from 5.8+/-0.2 to 4.4+/-0.3 mg/dl, p<0.05), while it remained unchanged in HD. A similar pattern of changes was detected in Ca x P.\n Enhancement of P removal, acutely amplifies the extent of PDR-P, but allows better control of Ca-P homeostasis in the medium term. This effect is likely to be dependent on the enhanced mobilisation of phosphate from a deep compartment.", "Middle molecules (MMs) and protein-bound solutes are poorly removed by conventional hemodialysis (HD). Hemodiafiltration (HDF) combines convection and diffusion in a single therapy and has been shown to be superior for the elimination of several small and larger retention molecules. Information on the elimination of protein-bound solutes during convective strategies is scarce. The primary aim of this randomized crossover study is to evaluate the influence of internal filtration, postdilution HDF, and predilution HDF on removal of the protein-bound solute p-cresol.\n Fourteen stable patients on regular thrice-weekly medium-flux HD therapy were assigned to 5 treatment periods of 2 weeks each for: HD with HF80(S); HD with FX80; postdilution HDF, 20 L, with FX80; predilution HDF, 20 L, with FX80; and predilution HDF, 60 L, with FX80 (all dialyzers from Fresenius Medical Care, Bad Homburg, Germany).\n As for the water-soluble solutes, elimination of p-cresol was better during HDF and increased with greater filtration volumes. Removal of beta2-microglobulin (beta2m) also was enhanced during HDF. However, the positive effect of convection was offset when high predilution substitution volumes were applied, probably as a result of dilution. Within each dialytic approach, removal of the MM beta2m and the protein-bound solute p-cresol was significantly less than that of the water-soluble molecules urea nitrogen and creatinine.\n Our data indicate that convection can provide superior protein-bound solute removal compared with high-flux HD. Our findings also suggest that better elimination of the unbound fraction is the most plausible underlying mechanism.", "Accumulation of larger molecular weight uraemic toxins molecules may have a negative effect on the cardiovascular and nutritional state of dialysis patients and influence uraemic symptomatology. Their clearance can be enhanced by the use of haemofiltration (HF).\n The effects of low-flux haemodialysis (HD) (ultrapure dialysate; polyamide membranes) and pre-dilution on-line HF (1:1 blood/substitution ratio; target filtration volume: 1.2 times body weight) on cardiovascular and nutritional parameters, interdialytic levels of uraemic toxins and quality of life (QOL; Laupacis questionnaire) were assessed during 1 year follow-up. Forty patients were randomized.\n After 1 year, 27 patients were eligible for analysis (HF: 13 patients; HD: 14 patients). Left ventricular mass index did not change in the HF patients (127+/-33 --> 131+/-36 g/m(2) after 12 months) or in the HD group (135+/-34 --> 138+/-32 g/m(2)). Also, there were no changes in pulse wave velocity, and 48 h systolic and diastolic blood pressures. Lean body mass, assessed by dual-energy X-ray absorptiometry, increased in the HF group (44.8+/-8.9 --> 46.2+/-9.6 kg; P<0.05), but not in the HD group (49.4+/-9.2 --> 50.6+/-8.8 kg), although differences between groups were not significant. Insulin-like growth factor-1 levels remained stable in the HF patients, but decreased in the HD group (P<0.05 between groups). QOL for physical symptoms improved in the HF group (4.2+/-1.2 --> 5.0+/-1.1; P<0.05 within the HF group and P = 0.06 between groups), but not in the HD group (4.0+/-1.0 --> 4.4+/-1.4). beta2-microglobulin, complement factor D and homocysteine decreased significantly in the HF but not in the HD group, whereas l-ADMA, leptin and advanced glycation end-products-related fluorescence did not change.\n No changes in cardiovascular parameters were observed during pre-dilution on-line HF compared with low-flux HD. Treatment with on-line HF resulted in marked changes in the uraemic toxicity profile, an improvement in physical well-being and a small improvement in nutritional state.", "The objective of the study was to compare the convective treatment modes, on-line hemofiltration (HF) and on-line hemodiafiltration (HDF), regarding cardiovascular tolerance and effects on blood pressure, when applied under similar conditions in stable dialysis patients.\n 39 clinically stable dialysis patients were treated with HD for 6 months (run-in period), followed by HF and HDF in random order for 2x6 months. Similar biocompatibility (same membrane and fluid quality), similar treatment time and urea Kt/V were achieved using AK100/200 ULTRA machines, polyamide membranes in low-flux and high-flux versions and appropriate adjustment of blood flow rate (Qb) and dilution ratio (Qb/Qinf). Predilution was used for HDF (target dilution ratio = 2/1 ) as well as for HF (target dilution ratio = 1/1).\n 30 patients completed the study; 5 dropped out for non-study related reasons and 4 for non-compliance. Treatment with HF in comparison to HDF showed fewer hypotension episodes during the sessions per patient and month (HF: 0.5, HDF 1.1; p = 0.017), less plasma expander administration per patient and month (HF: 35.9 ml, HDF: 103.1 ml; p = 0.035), fewer episodes of intra-session headache (HF: 0.1, HDF: 0.4; p = 0.06), and higher pre-session MAP (HF: 98.4 mmHg, HDF: 93.8 mmHg; p = 0.037). No significant difference was found in inter-treatment weight gain, post-session MAP, or pre-session plasma sodium.\n HF and HDF provide good control of intra-session symptoms and blood pressure in stable patients. Treatment with HF resulted in a significant reduction in intra-session hypotension and a slight but significant increase in pre-session MAP, caused by an increase in systolic BP without any effect on the prevalence of hypertension or the dose of antihypertensive drugs, all compared to HDF.", "Efficient removal of total body burden beta 2-Microglobulin (beta 2-M) in uremia is a continuing challenge, as dialysis-related amyloidosis represents a major complication of chronic renal replacement therapy. To investigate long-term beta 2-M removal we studied 3 groups of stable end-staged renal failure patients over a period of 4 years; we compared low flux (cuprophane) hemodialysis (n = 12), high flux (polysulfone) hemodialysis (n = 12) and hemofiltration using high flux polysulfone (n = 8). In contrast to the cuprophane membrane, the polysulfone membrane eliminated considerable amounts of beta 2-M. This was associated with a sustained reduction of predialysis serum beta 2-M-levels (by 20%). Compared with high flux hemodialysis, hemofiltration provided a 50% higher elimination of beta 2-M. Thus, our long-term evaluation of beta 2-M removal suggests that hemofiltration rather than hemodialysis may be the treatment of choice for delaying the incidence of dialysis-related amyloidosis.", "Hemodiafiltration (HDF) and more recently acetate-free biofiltration (AFB) have shown good blood purification and cardiovascular stability in young and middle-aged hemodialysis patients. It is not clear if this is also valid for elderly patients. Twelve patients aged more than 70 years (mean age +/- SD, 76 +/- 4 years) on regular dialysis for at least 5 months were treated with bicarbonate dialysis (BD), HDF, or AFB in a randomized sequence and prospectively followed for 6 months (72 dialysis sessions/patient) for each procedure. The dialysis solution (containing bicarbonate), blood flow rate, and dialysate flow rate were the same with all the methods. During HDF and AFB solutions containing bicarbonate at a concentration of 27 to 30 mEq/L and 145 mEq/L, respectively, were infused postdilution at a rate of 66 +/- 7 mL/min and 2.81 +/- 0.12 L/hr, respectively. During the period of observation we evaluated the number of intradialytic hypotensions, the episodes of nausea, vomiting, headache (dialysis intolerance), body weight, the interdialysis weight gain, the duration of the dialysis session, the number of hospitalizations/patient, and the length of hospitalization/patient. At the end of each observation period we determined: Kt/V, protein catabolic rate, acid base balance, serum creatinine, serum calcium, serum phosphorus, alkaline phosphatases, and serum intact parathyroid hormone. After the switch from BD to either HDF or AFB, the results have shown a significant reduction of dialysis hypotension episodes (18 percent on BD, 14 percent on HDF, and 13 percent on AFB; BD v HDF, P = 0.001; BD v AFB, P = 0.0001; and HDF v AFB, P = NS) and of dialysis intolerance (3.3 percent on BD, 1.3 percent on HDF, and 1.1 percent on AFB; BD v HDF, P = 0.021; BD v AFB, P = 0.019; and HDF v AFB, P = NS). Kt/V improved significantly after the switch from BD to either HDF or AFB (1.17 +/- 0.06 on BD, 1.32 +/- 0.12 on HDF, and 1.32 +/- 0.13 on AFB; BD v HDF, P = 0.021; BD v AFB, P = 0.003; HDF v AFB, P = NS). Protein catabolic rate also improved in HDF and AFB compared with BD (0.90 +/- 0.12 on BD, 1.03 +/- 0.15 on HDF, and 1.04 +/- 0.14 on AFB; BD v HDF, P = 0.001; BD v AFB, P = 0.009; and HDF v AFB, P = NS). AFB showed a better correction of acidosis compared either with BD or HDF (serum bicarbonate, 20.3 +/- 1.1 mEq/L on BD, 20.8 +/- 2.2 mEqL on HDF, and 22.2 +/- 2.4 mEq/L on AFB; BD v HDF, P = NS; BD v AFB, P = 0.01; and HDF v AFB, P = 0.030). The other parameters observed did not differ. In conclusion HDF and AFB show a better dialysis efficiency and a better hemodynamic tolerance compared with BD. This fact is associated with an improvement in protein intake as assessed by kinetic criteria. Acetate-free biofiltration has the further advantage of a better control of the acid-base balance compared with BD and HDF. HDF and AFB are useful dialytic options to traditional BD hemodialysis even in patients older than 70 years.", "Activation of polymorphonuclear neutrophils (PMNs) and monocytes has been described during hemodialysis (HD), which results in the release of reactive oxygen species and cytokines. Acetate-free biofiltration (AFB) has been shown to cause less monocyte activation and cytokine release than bicarbonate HD (BHD). No data are available to date on the effect of AFB on PMN activation.\n We studied ex vivo superoxide anion release by PMNs isolated from nine patients treated in random order with AFB or BHD (three sessions each). Plasma interleukin-1beta (IL-1beta) levels and the nitric oxide (NO) synthetic pathway also were evaluated. A polyacrylonitrile (AN69; Hospal, Bologna, Italy) dialyzer was used for both treatments. Fourteen healthy volunteers were used as controls. Blood samples were drawn predialysis and 5 and 15 minutes after starting dialysis to obtain plasma and PMNs.\n Neither ex vivo superoxide anion release nor blood PMN count was affected by AFB. Conversely, a peak in superoxide anion production associated with a decrease in PMN count was observed at 5 minutes during BHD. Results of superoxide anion production by control PMNs exposed in vitro to AFB or bicarbonate dialysis bath or Hank's balanced salt solution supplemented with bicarbonate or acetate indicated that BHD-induced PMN activation could be attributed to the amount of bicarbonate present in the dialysis bath. IL-1beta plasma levels did not change during dialysis with AFB and were numerically higher at 5 and 15 minutes with respect to predialysis values during BHD. Uremic plasma obtained during either AFB or BHD induced greater NO synthesis by human umbilical vein endothelial cells than control plasma.\n AFB, unlike BHD, does not cause PMN and monocyte activation, which could have a positive impact on dialysis-associated cardiovascular disease of dialyzed patients.\n Copyright 2002 by the National Kidney Foundation, Inc.", "Morbidity and mortality rates in diabetic patients on regular dialysis treatment (RDT) are higher than in non-diabetic-subjects on RDT. Moreover, diabetic patients experience an intradialitic morbidity unacceptably higher than in patients with other causes of terminal renal failure. The aim of the present investigation was to compare standard bicarbonate haemodialysis (BHD) with acetate-free biofiltration (AFB) in a group of 41 diabetic patients stable on dialysis treatment for 25 +/- 22 months.\n Twenty-four type II and 17 type I diabetic patients, all requiring insulin therapy, were included and were followed for 1 year in a 6-month cross-over randomized study for both methods. The analysis was carried out on dialysis symptoms, interdialysis symptoms, and nutritional status, and the multivariate analysis of variance for repeated measures on the same subjects in the two techniques was used.\n AFB significantly reduced dialytic and extradialytic symptoms (P=0.003 and 0.001 respectively). Cardiovascular collapses decreased by 43%, and other dialysis symptoms showed a similar trend (-35%). The interdialysis symptoms decreased by 28% and were accompanied by an increase in subjective wellbeing (39%) when patients were switched from traditional haemodialysis to AFB. Acid base control was better with AFB (P=0.01), both at the beginning and during the session. Slightly significant differences were also obtained for Kt/V (AFB 1.48 +/- 0.29 vs BHD 1.38 +/- 0.30), while no significant difference was noted with respect to sodium mass balance, nutritional status, calorie-protein intake, nPCR, blood glucose profile, and insulin requirements. The number of hospital admissions and the mortality rate, which were much lower during the AFB than the BHD period, were not analysed statistically.\n AFB allows better control of some metabolic aspects, reduces intra- and extradialysis symptoms, and improves patient quality of life. Whether the long-term prognosis can be improved by AFB remains to be established with further studies.", "The accumulation of beta2-microglobulin (beta2-M) in long-term dialysis patients may lead to dialysis amyloidosis. In this respect, the removal with different modes of on-line haemodiafiltration (HDF) of beta2-M was studied. Long-term clinical observations in patients with more than 10 years of dialysis, treated mainly with biocompatible and highly permeable membranes and in the last years with on-line HDF are also reported.\n In the first part of this report, the reduction ratios and clearances of beta2-M, blood urea nitrogen, creatinine and phosphorus (P) of on-line HDF with 40 to 120 ml/min replacement fluid are compared with bicarbonate haemodialysis (HD). In the second part, we investigated 16 patients with more than 10 years of dialysis treatment. The prevalence of dialysis amyloidosis and the mean values for serum albumin, serum total cholesterol, HDL and LDL cholesterol and parathyroid hormone are reported, as well as the mean dose of erythropoietin.\n In the first part with on-line HDF, starting from HDF 60 ml/min a significantly higher beta2-M reduction ratio and clearance vs HD is noted. In HDF100 (i.e. with 241 replacement volume per 4-h treatment) vs HD, a beta2-M reduction ratio of 72.7% vs 49.7% (P= 0.0000) and a beta2-M clearance of 116.8 vs 63.8 ml/min (P=0.0000) was obtained. Comparing HDF120 with HDF100, there is a significantly higher beta2-M clearance with the former (P<0.005), although the beta2-M reduction ratio was not significantly better. In the HDF120 session the amount of beta2-M in the total dialysate was 292 mg per session. If one adds the known 17% adsorption on the polysulfone membrane, a total of 341.6 mg beta2-M per session is removed, which adds up to 1024.8 mg a week. Concerning the small molecules, our results with HDF100 also show a higher creatinine and especially P clearance vs HD. In the second part with 16 patients with more than 10 years of dialysis treatment (mean 14 years 1 month), the mean time on HDF amounted to 39.5% of the total treatment time. In four patients only biocompatible and highly permeable membranes were used, AN69 and mainly polysulfone, and in four other patients these membranes were used for more than 95% of the treatment time. Therefore, it is not surprising that the prevalence of carpal tunnel syndrome was only 12.5% in the patients after 10 years of dialysis. Twenty-five percent of these patients met the criteria for diagnosis of beta2-M bone-amyloidosis, proposed by van Ypersele de Strihou et al., but without a retrospective X-ray analysis. The mean predialysis beta2-M value was 29.6 mg/l. The mean values for serum albumin, serum total cholesterol, HDL and LDL cholesterol were within normal limits. For the parathyroid hormone a mean of 287.5 pg/ml was found. Subtotal parathyroidectomy was performed in five patients. The mean dose of 43 U erythropoietin/kg per session is comparable with those reported in the literature. Conclusions. Like Canaud, in our renal unit, treatment with on-line HDF with a highly permeable and biocompatible membrane has proven to be an efficient, well-tolerated and safe technique. Furthermore it leads to a low prevalence of dialysis amyloidosis and a superior P clearance. However, continuous attention must be paid to an on-line sterile and apyrogenic dialysate. Although on-line HDF is undoubtedly a more optimal approach of chronic dialytic treatment, it also carries a higher cost, which is currently evaluated to be nearly US$11 per session.", "Online hemodiafiltration (online HDF) and acetate-free biofiltration (AFB) are 2 innovative renal replacement therapies. Convincing evidence has shown that both techniques are superior to conventional hemodialysis in many aspects. The aim of the present investigation was to compare online HDF and AFB in 12 stable maintenance hemodialysis patients in a prospective, randomized crossover trial. Twelve stable dialysis patients, age 49.7 +/- 11.3 years and on dialysis for 83.5 +/- 76.7 months, were treated prospectively and randomly by either AFB, predilution HDF (pre-HDF), or postdilution HDF (post-HDF) for a total of 36 weeks using exclusively F60S high-flux dialyzers. Routine blood biochemical tests, bone metabolism parameters, and clearance for both small and larger molecular weight substances were measured at defined intervals. During the trial period inter- and intradialysis symptoms, e.g., hypotensive episodes and intradialysis arterial blood gas analyses, were recorded. Both online HDF and AFB were well accepted by the overwhelming majority of patients and also by the dialysis staff. Pretreatment sodium, total and ionized calcium, chloride, bicarbonate, and urea did not differ within or between the 3 treatment groups. Potassium increased slightly in HDF patients while phosphate and beta2-microglobulin (beta2-M) decreased in all groups. After dialysis, AFB patients exhibited a significantly higher bicarbonate concentration and lower potassium level when identical potassium concentrations in dialysate were used. Patients receiving AFB manifested less intradialysis partial pressure of oxygen drop and partial pressure of carbon dioxide rise than those on HDF treatments. HDF treatments could afford higher single-pool and double-pool Kt/V, higher effective urea and beta2M clearance, and lower total interdialysis symptom scores than the AFB treatment method. While bone metabolism parameters did not differ between the 3 dialysis modalities, some parameters such as deoxypyridinoline in HDF and osteocalcin, pyridinoline, and deoxypyridinoline in AFB deteriorated at the end of the crossover study. Aluminum concentration decreased progressively to about one-third of prestudy values at the end of the study with all 3 treatments. AFB was associated with a lower predialysis mean arterial pressure (MAP), a smaller drop in MAP during treatment, and similar hypotension episodes compared with the 2 HDF treatments. Albumin concentration showed a trend to decrease during the first 2 months of the trial period followed by a slight increase thereafter but still significantly lower than initial value at the end of crossover. Both online HDF and AFB share most of the features of optimal renal replacement therapy. Online HDF is superior to AFB in such aspects as increased delivered dialysis dose both for small and larger molecular weight toxins and less interdialysis symptoms. On the other hand, AFB is associated with a smaller effect on arterial blood gas values and improved intradialysis hemodynamic tolerance. Some dialysis-related symptoms and complications in the case of our AFB practice could be attributable, at least in part, to low dialysate calcium level.", "In spite of the better efficiency of on-line hemodiafiltration (HDF) compared with conventional hemodialysis (HD), it is relatively expensive. The aim of this study was to assess the advantages in the biochemical, hemodynamic and clinical effects in uremic patients treated with on-line HDF and with different frequencies of combination high-flux HD.\n One hundred eleven patients were divided into four groups receiving different frequencies of on-line HDF (thrice, twice, once per week) and high-flux HD.\n Hemodynamic parameters including maximum drop of systolic blood pressure, episodes of symptomatic hypotension and mean saline infusion volumes during dialysis were reduced when frequencies of on-line HDF were increased. Significant improvements in urea kinetic were observed when frequencies of on-line HDF were increased. On-line HDF significantly reduced the amount of erythropoietin needed and improved intra- and inter-dialysis symptoms, physical well-being, menstruation and skin pigmentation when frequency of HDF is increased to three time per week.\n On-line HDF offers a better cardiovascular stability and clinical improvement. Thrice weekly on-line HDF offers a significant benefit when compared with lower frequencies of HDF per week and high-flux HD.", "The authors monitored, for a period of 12 months, anemia-, nutrition-, and free radical-related parameters and the rHuEPO dose required to maintain target hemoglobin (Hb) in 20 patients with chronic renal failure. Ten patients each were randomized for treatment by either acetate-free biofiltration (AFB) or low-flux hemodialysis (HD). At baseline, Hb levels were 102+/-2 (AFB) vs. 98+/-2 g/L (HD) (not significant difference, NS), the rHuEPO dose was 4050+/-976 vs. 5100+/-1538 lU/week (NS). Compared with baseline and with HD, lower rHuEPO doses were required during AFB at months 8, 9, 10 and 11, and 12 when they were 2100+/-510 (AFB) vs. 6000+/-1153 (HD), p=0.008. Prealbumin, transferrin and cholinesterase levels rose in the AFB group. Kt/V, albumin, transferrin saturation, aluminium, bicarbonate in serum, superoxide dismutase and glutathione peroxidase in erythrocytes, and malondialdehyde and antioxidant capacity in plasma did not differ between the AFB and HD groups. In terms of anemia control, AFB using an AN69 membrane was found to be more advantageous than low-flux HD, AFB improves some nutritional parameters. The compared methods do not differ in their effect on lipid peroxidation and the antioxidant system.", "The effect of acetate dialysis (AD), bicarbonate dialysis (BD), and acetate-free biofiltration (AFB) on nitric oxide (NO) synthesis and the implications for dialysis hypotension was studied. The finding that uremic plasma is a potent inducer of NO synthesis by endothelial cells in vitro suggested that the cardiovascular instability of dialysis patients might result from excessive NO formation. Cardiovascular instability is more frequent in patients undergoing AD than BD. To see whether these differences were attributable to NO, we studied the NO synthetic pathway ex vivo in patients undergoing different dialysis procedures. Five patients were treated, in a random order, with AD, BD, and AFB, a technique using a buffer-free dialysate and postdilution of a sterile bicarbonate solution. Each type of dialysis was used for 1 week, comprising three dialysis sessions. A polyacrylonitrile dialyzer was used for all three methods. Before and after the third dialysis, plasma was collected, added to [3H]L-arginine, and incubated with human umbilical vein endothelial cells (HUVECs) for 24 hours. NO synthesis was evaluated as [3H]L-citrulline formation. Plasma concentrations of interleukin-1beta (IL-1beta), a potent inducer of inducible NO synthase (iNOS) in endothelial cells, were also measured. Plasma collected from patients after AD stimulated endothelial NO synthesis more than plasma from the same patients before the dialysis session (pre-AD, 0.173+/-0.028 nmol/10(5) cells v post-AD, 0.280+/-0.093 nmol/10(5) cells; P < 0.05). A slight, although not significant, increase was also observed when HUVECs were incubated with plasma drawn after BD (pre-BD, 0.151+/-0.014 nmol/10(5) cells; post-BD, 0.230+/-0.055 nmol/10(5) cells). AFB did not aggravate the stimulatory effect of uremic plasma on endothelial NO synthesis (pre-AFB, 0.184+/-0.038 nmol/10(5) cells; post-AFB, 0.189+/-0.040 nmol/10(5) cells). Plasma IL-1beta was greater (P < 0.01) after AD than after BD and AFB (post-AD, 0.234+/-0.028 pg/mL; post-BD, 0.124+/-0.019 pg/mL; post-AFB, 0.120+/-0.013 pg/mL). With AD, there was a greater intradialytic decrease in systolic blood pressure than with BD or AFB. Weight and blood volume loss and sodium balance were similar in AD, BD, and AFB. These data were consistent with the possibility that NO and cytokines, released in excessive amounts during AD, may contribute to hemodynamic instability.", "This study compared the acute and chronic effects on cardiac function of treatment with hypertonic hemodiafiltration (H HDF) and hemodialysis (HD). Cardiac function was assessed before, during and after a run of H HDF and HD using echocardiography and impedance cardiography in 10 patients in a randomized cross-over sequence, two months after stabilization on each treatment. Blood biochemistry was performed before and after each run. Ejection fraction and fractional shortening were significantly higher before the H HDF run, compared to the HD run, and this difference persisted during and after the treatment runs (both P less than 0.05). There was a corresponding significant difference in the increase of the velocity of circumferential fiber shortening and in the reduction of end systolic diameter during and after H HDF (P less than 0.05). Heart rate, stroke volume, cardiac output, systemic vascular resistance and mean arterial pressure did not differ significantly between the two treatments. Plasma calcium and bicarbonate were significantly higher (P less than 0.03) at the start of H HDF and this difference was enhanced at the end of the run. In conclusion, H HDF compared with HD, is associated with a better myocardial function in both the short and long term treatments. The evidence suggests that this may be due to improved levels of plasma calcium, bicarbonate, and/or the removal of an as yet unidentified myocardial toxin.", "There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage (in terms of treatment tolerance, nutritional parameters and pre-treatment beta-microglobulin levels) over a traditional membrane (Cuprophan). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan hemodialysis (Cu-HD), low-flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 +/- 10.46 mg/liter (23%) and in hemodiafiltration of 6.35 +/- 12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes (P = 0.032). The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications.", "The discussion about the pathogenesis of renal anaemia, whether it is primarily due to relative erythropoietin (Epo) deficiency or to uraemic inhibition of erythropoiesis, is still open. Although it has so far not been possible to identify or isolate a substance retained in uraemia with a suppressive action directed specifically against red-cell production, dialysis therapy can improve the effect of both residual endogenous Epo and exogenous rHuEpo. To what extent the mode and/or the dose of dialysis influence Epo efficacy is as yet poorly understood.\n This study was performed as a single-centre trial. The protocol included a run-in period of 4 months followed by a prospective cross-over study including 6 months each of acetate-free biofiltration (AFB) with a high-flux biocompatible membrane and standard bicarbonate dialysis (BD) with a low-flux cellulosic membrane in a random sequence. AFB is a haemodiafiltration technique based on a continuous post-dilution infusion of a sterile isotonic bicarbonate solution. At the start of the run-in period (and for the entire length of the study), rHuEpo administration was withdrawn; patients whose haemoglobin (Hb) levels dropped at a level <8.0 g/dl at one single monthly check, had to be withdrawn from the study. A blood sample was collected every month for the blood gas analysis and for the determination of blood urea nitrogen, serum creatinine, sodium, potassium, calcium, phosphorus, Hb, erythrocyte, reticulocyte, leukocyte and thrombocyte cell counts, mean globular volume and haematocrit. An equilibrated single pool Kt/V(urea)>1.2 was mandatory in both treatment modalities. Serum iron, total iron-binding capacity, and ferritin were checked every 3 months.\n Twenty-three of 137 haemodialysis patients were considered eligible for the trial on the basis of the entry criteria. Of these, 15 volunteered and only 10 completed the study. No significant differences in the haematological indices, in the biochemical parameters assessing body iron stores, or in i.v. iron dosage was observed when comparing AFB with BD treatments. The equilibrated single pool Kt/V(urea) was always >1.2 and in no case was a significant difference observed when comparing AFB with BD treatments. Treatment time was significantly different between the two treatments (262+/-2 min in BD and 249+/-1 in AFB, P<0.0001). Neither pre- nor post-dialysis systolic and diastolic blood pressures, pre-dialysis serum bicarbonate and pH, pre-dialysis serum sodium, potassium, calcium, or phosphorus were significantly different when comparing the two treatment modalities. All 10 patients completed the 1-year follow-up without any major side-effects.\n Our study did not show any improvement of anaemia when treating a highly selected patient group, in the absence of any Epo therapy, with AFB compared with standard BD. Even though these conclusions cannot be extended in toto to the entire dialysis population, in which there is a large proportion of Epo-treated patients with Hb levels around 11 g/dl, we may nevertheless conclude that when patients are well selected, adequately dialysed, and not iron- and/or vitamin-depleted, the effect of a haemodiafiltration technique with a high-flux biocompatible membrane is less than might be expected from the results of uncontrolled studies.", "Some of the morbidity associated with chronic hemodialysis is thought to result from retention of large molecular weight solutes that are poorly removed by diffusion in conventional hemodialysis. Hemodiafiltration combines convective and diffusive solute removal in a single therapy. The hypothesis that hemodiafiltration provides better solute removal than high-flux hemodialysis was tested in a prospective, randomized clinical trial. Patients were randomized to either on-line postdilution hemodiafiltration or high-flux hemodialysis. The groups did not differ in body size, treatment time, blood flow rate, or net fluid removal. The filtration volume in hemodiafiltration was 21 +/-1 L. Therapy prescriptions were unchanged for a 12-mo study period. Removal of both small (urea and creatinine) and large (ss(2)-microglobulin and complement factor D) solutes was significantly greater for hemodiafiltration than for high-flux hemodialysis. The increased urea and creatinine removal did not result in lower pretreatment serum concentrations in the hemodiafiltration group. Pretreatment plasma beta(2)-microglobulin concentrations decreased with time (P< 0.001); however, the decrease was similar for both therapies (P = 0.317). Pretreatment plasma complement factor D concentrations also decreased with time (P<0.001), and the decrease was significantly greater with hemodiafiltration than with high-flux hemodialysis (P = 0.010). The conclusion is that on-line hemodiafiltration provides superior solute removal to high-flux hemodialysis over a wide molecular weight range. The improved removal may not result in lower pretreatment plasma concentrations, however, possibly because of limitations in mass transfer rates within the body.", "Current methods of renal replacement therapy lead only to an insignificant removal of larger, potentially toxic, substances, which are excreted by healthy kidneys. On-line preparation of substituate from dialysate and the use of high-flux membranes allow substantial convective removal of such substances. A modified on-line haemodiafiltration method with the use of a large membrane surface and a high convective part was chosen to test whether the elimination of larger substances, such as low-molecular-mass proteins, has a clinical impact.\n In a prospective, controlled study over 24 months, 44 unselected chronic dialysis patients were randomized to undergo either low-flux haemodialysis (HD; n = 21) or haemodiafiltration (HDF; n = 23). To eliminate confounding factors, low-molecular efficacy was matched (Kt/V 1.8), and the same membrane material (polysulfone), ultrapure dialysate and the same treatment duration (4.5 h) were applied to each group.\n Morbidity, mortality, blood pressure, dialysis-associated hypotensive episodes, haematocrit and erythropoietin dose did not differ between the groups. The same was true for body weight and, accordingly, bioimpedance values, clinical hydration score, skinfold thickness, plasma albumin, prealbumin and transferrin. beta2-Microglobulin in the plasma did not change in the HD group and varied between 32 and 43 mg/l throughout the 2 years. In HDF, beta2 microglobulin decreased from similar values to 18 mg/l predialysis (P<0.01) in the first 6 months of HDF treatment and then remained constant during the remaining 18 months.\n In the absence of any clinical marker of uraemic toxicity the removal of larger molecules over the time-span of 2 years during HDF had no clinical implication compared with extremely (and for routine practice unrealistically) well-dialysed patients with low-flux HD. In the absence of any side-effects of on-line HDF and supposing that plasma beta2-microglobulin is a marker of morbidity, on-line HDF ensures an excellent dialysis quality which apparently takes time to translate into measurable clinical sequelae.", "Nine patients on regular dialysis were studied, in a cross-over format comparing hemodialysis (HD) and hemofiltration (HF), to identify potential mechanisms of the disparate hemodynamic responses. Dialysis and substitution fluid composition (high sodium, acetate), treatment time, fluid loss rate, and membrane type (AN 69) were matched. Cardiac output was determined by changes in thoracic electrical bioimpedance. Cardiac output remained stable during HF but increased during HD (p < 0.001, HD vs. HF), despite a parallel reduction in stroke volume. The heart rate response was significantly greater during HD relative to HF (p < 0.01). Systemic vascular resistance remained stable during HF but decreased significantly during HD (p < 0.05). Although there was a modest fall during HD, the difference in blood pressure at the end of treatment between HD and HF was not significant. Comparable increases in body temperature were observed during both treatments. Plasma catecholamines increased in parallel during HD and HF and following orthostatic stimulation at the end of treatment, and extracorporeal catecholamine clearances were similar. The values for serum sodium, total CO2, anion gap, potassium, and hematocrit at the end of treatment were similar, whereas total serum calcium was significantly greater following HD. There were no significant differences in indices of myocardial contractility or central blood volume. These results suggest that the disparate hemodynamic responses to fluid and solute removal during HD and HF can be dissociated from changes in osmolality or venous tone, membrane bioincompatibility, thermal stress, or differences in acetate delivery or catecholamine release. The explanation for the disparate hemodynamic responses between these two treatment modalities remains unclear. A role for an as yet unidentified vasodilatory substance generated during dialysate exposure, or convectively removed during hemofiltration, remain intriguing possibilities.", "Acetate free biofiltration (AFB) provides a well-tolerated and efficient renal replacement therapy. Replacement of most of the acetate by bicarbonate in standard hemodialysis has resulted in a decrease in intradialytic hypotensive episodes. This has been attributed to a decrease in the acetate-induced impairment of myocardial contractility. The aim of the present study was to investigate whether the total absence of acetate in AFB would further enhance dialysis stability and improve cardiovascular status.\n In a long-term, randomized trial we included 11 patients on AFB and 9 patients on bicarbonate hemodialysis (HD) for one year. Patients were matched for age, sex and urea reduction rate, but not for the presence of hypertension or cardiovascular history. During each dialysis session blood pressure was measured automatically and the presence of significant hypotension was recorded. Antihypertensive medication was registered every three months. Before and at the end of the study M-mode echocardiography was performed and left ventricular mass index (LVMi) was calculated. Every six months serum lipids were measured.\n At baseline, mean arterial pressure (MAP) before and after dialysis, the percentage of hypotensive dialyses, LVMi and serum lipids did not differ between AFB and HD. Pre-dialysis MAP decreased in AFB (from 112.5 to 107 mmHg) and increased in HD (from 101.7 to 105.3 mmHg; p = 0.01, HD versus AFB). Postdialysis MAP remained stable in both groups (AFB 91.6 mmHg at 0 months and 90.6 mmHg at 12 months, for HD respectively 83.9 and 86.5 mmHg, NS). The percentage of hypotensive dialyses did not differ significantly between the groups during the study. LVMi decreased in AFB from 195.4 to 162.1 gr/m2 and increased in HD patients from 153.8 to 182.5 gr/m2 (p = 0.03 HD versus AFB). The number of antihypertensive medications per patient did not differ between groups. Serum lipids remained unchanged during the trial.\n In conclusion, AFB provided better control of pre-dialysis MAP compared to HD, and stable postdialysis MAP. The percentage of dialysis sessions with hypotension did not differ. LVMi decreased significantly in AFB, but rose in HD." ]

[ "15326246", "7605179" ]

[ "Strength training and albuterol in facioscapulohumeral muscular dystrophy.", "Strength training in patients with myotonic dystrophy and hereditary motor and sensory neuropathy: a randomized clinical trial." ]

[ "In animals and healthy volunteers beta2-adrenergic agonists increase muscle strength and mass, in particular when combined with strength training. In patients with facioscapulohumeral muscular dystrophy (FSHD) albuterol may exert anabolic effects. The authors evaluated the effect of strength training and albuterol on muscle strength and volume in FSHD.\n Sixty-five patients were randomized to strength training of elbow flexors and ankle dorsiflexors or non-training. After 26 weeks albuterol (sustained-release, 8 mg BID) was added in a randomized, double-blind, placebo-controlled design. Primary outcome was maximum voluntary isometric strength (MVIC) at 52 weeks. Secondary outcomes comprised dynamic strength and muscle volume.\n Training and albuterol were well tolerated. Training of elbow flexors did not result in a significant effect on MVIC, but dynamic strength improved significantly. Elbow flexor MVIC strength increased significantly in albuterol vs placebo treated patients. Ankle dorsiflexor strength decreased in all groups. Eleven out of twelve non-trained muscles in the albuterol group showed a positive effect on MVIC compared to the placebo group (p < 0.05 in seven muscle groups). Muscle volume decreased in the placebo-treated, and increased in the albuterol-treated patients. No synergistic or antagonistic effects were observed between training and albuterol.\n In FSHD strength training and albuterol appear safe interventions with limited positive effect on muscle strength and volume. Consequences of prolonged use are presently unclear, which precludes routine prescription.", "A randomized clinical trial on the effects of strength training was performed in myotonic dystrophy (MyD) patients and patients with hereditary motor and sensory neuropathy (HMSN). Training and most measurement tools involved the proximal lower extremity muscles. The participants trained 3 times a week for 24 weeks with weights adapted to their force. Strength was evaluated by isokinetically measured knee torque. Fatiguability was assessed by the time an isometric contraction could be sustained. Functional performance was measured by timed motor performance and by questionnaires on functional performance. Serum myoglobin (Mb) levels were determined to detect changes in muscle fiber membrane permeability. The MyD group included 33 participants, and the HMSN group included 29 participants. Within each diagnostic group, patients were individually matched and subsequently randomized for treatment allocation. In the MyD patients, none of the measurement techniques showed any training effect. Neither were there signs of deterioration caused by the training. In the HMSN group, knee torques increased. Timed motor performance did not change, although the questionnaires showed an improvement on items related to upper-leg function. Mb levels did not change significantly as a result of the training. In conclusion, the MyD group showed neither positive nor negative effects of the training protocol, whereas the training produced a moderate increase in strength and leg-related functional performance in the HMSN group." ]

[ "15157791", "10717778", "4933978", "11124360", "12499030", "4185963", "10036600", "4871666" ]

[ "Cycle control, quality of life and acne with two low-dose oral contraceptives containing 20 microg ethinylestradiol.", "Comparison of efficacy, cycle control, and tolerability of two low-dose oral contraceptives in a multicenter clinical study.", "Treatment of functional dysmenorrhea; a double-blind study.", "Latin american experience with two low-dose oral contraceptives containing 30 microg ethinylestradiol/75 microg gestodene and 20 microg ethinylestradiol/150 microg desogestrel.", "Primary dysmenorrhea treatment with a desogestrel-containing low-dose oral contraceptive.", "Primary dysmenorrhea: combination vs sequential therapy.", "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.", "Dysmenorrhoea unrelieved by an oral contraceptive." ]

[ "Poor cycle control and tolerability can be reasons for irregular pill intake. This study compared the tolerability of two low-dose oral contraceptives and their effect on cycle control.\n In this open, group-comparative, randomized multicenter trial in Germany and the Netherlands, women received either 20 microg ethinylestradiol plus 150 microg desogestrel (20EE/DSG; n = 500) or 20 microg ethinylestradiol plus 100 microg levonorgestrel (20EE/LNG; n = 498) for six treatment cycles. Cycle control, dysmenorrhea and premenstrual syndrome (PMS) were assessed using diary cards. Tolerability was assessed using the self-administered questionnaires Psychological General Well-Being Index (PGWBI) and the Profile of Mood States (POMS). Acne was assessed by objective (acne counts) and subjective (no, moderate, mild, severe) acne scoring of the facial area at baseline and treatment cycles 1, 3 and 6.\n A total of 404 (78.1%) and 384 (75.3%) women in the 20EE/DSG and 20EE/LNG groups, respectively, completed the trial. The occurrence rate of irregular bleeding and spotting was statistically significantly higher with 20EE/LNG than with 20EE/DSG (0.18 vs. 0.13; p < 0.05). The mean number of bleeding-spotting days per cycle was statistically significantly higher with 20EE/LNG than with 20EE/DSG (0.63 vs. 0.48; p < 0.05). Early withdrawal bleeding was more frequent with 20EE/LNG (0.15 vs. 0.08; p < 0.005), whereas continued withdrawal bleeding was more frequent with 20EE/DSG (0.32 vs. 0.45; p < 0.001); absence of withdrawal bleeding was comparable (0.06 vs. 0.04, respectively). Thirteen subjects in the 20EE/LNG group and three in the 20EE/DSG group discontinued due to unacceptable bleeding (p < 0.05). Dysmenorrhea and PMS decreased comparably in both groups. There were no differences between groups for the mean total scores of PGWBI or POMS at all time-points. Fewer acne lesions were counted with 20EE/DSG vs. 20EE/LNG after six cycles (p < 0.05). The subjective acne scores supported this finding.\n 20EE/DSG provided better cycle control than 20EE/LNG with less treatment discontinuation due to unacceptable bleeding. There were no apparent differences between the two groups regarding tolerability and quality of life. There was less acne with 20EE/DSG.\n Copyright 2004 Elsevier Inc.", "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.", "nan", "The objective of this study was to compare cycle control, efficacy and tolerance of an oral contraceptive containing 20 microg ethinylestradiol and 150 microg desogestrel with a preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene. This study involved 342 women and 4104 cycles use in Argentina, Brazil, Chile, and Mexico. Contraceptive efficacy was good with both formulations. Two pregnancies occurred in the desogestrel group but were not due to method failure. With respect to cycle control, the incidence of intermenstrual bleeding was higher during the first 3 cycles in the desogestrel group; it was significant (p <0.01) during the first 3 days of the cycle for a normal or heavy bleeding only in the Mexican group. Amenorrhea was not reported for any group, but the incidence of dysmenorrhea was significantly higher (p <0.01) in the Brazilian desogestrel group (13.8%) and was significantly lower (p <0.01) in the Mexican gestodene group (8.5%). Adverse events were similar in all the countries with headache, breast tension, and nausea, the most frequently reported symptoms. The range of mean increase in body weight varied from 0.2 kg in the Argentine group to 2.6 kg in the Chilean group (95% confidence limit, +/- 2.51) in the gestodene group, and 0.2 kg in the Argentine group to 2.5 kg in Brazilian group (95% confidence limit, +/- 2.36) in the desogestrel group. Fifteen women discontinued because of headache, but there were no significant differences between the groups regarding discontinuation for this and other medical or non-medical reasons. Both oral contraceptive preparations are reliable and well tolerated, and both have favorable effects on control cycle.", "This randomized, double-blind, placebo-controlled exploratory study examined the efficacy and safety of a low-dose oral contraceptive (Mircette), desogestrel/ethinyl estradiol [DSG/EE] and ethinyl estradiol [EE]) in relieving the symptoms of dysmenorrhea. Twenty-three clinics in the United States enrolled 77 women (age < or =32 years) with primary dysmenorrhea documented for at least four consecutive cycles. Forty participants received DSG/EE&EE and 37 received placebo for four consecutive 28-day cycles. The intensity of menstrual-related distress was measured with the Menstrual Distress Questionnaire (MDQ). Patient diaries were used to assess number of school/work days missed as well as the use of rescue medication. Participants receiving DSG/EE&EE recorded reduced menstrual pain severity, lower total MDQ scores, and significantly less menstrual cramping. No significant change in bloating, anxiety, loneliness, weight gain, or acne was reported. The DSG/EE&EE formulation shows promise for the treatment of primary dysmenorrhea and was well tolerated by the participants in this study.\n Copyright 2002 Elsevier Science Inc.", "nan", "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.", "nan" ]

[ "3307283", "524479" ]

[ "Hyperextension injuries of the PIP finger joint. Comparison of early motion and immobilization.", "[Hyperextension injuries of the volar fibrocartilage in the proximal interphalangeal joints of the fingers]." ]

[ "In a prospective study of traumatic lesions of the volar fibrocartilage of the PIP joint, 56 patients were randomized to treatment by immobilization for 3 weeks and 56 patients, to purely analgetic treatment without immobilization. Seventy-eight patients were reexamined 6 months later and 77 patients, in a follow-up study 2-3 years after the injury. No difference was found between the two groups with respect to subjective complaints or objective signs.", "nan" ]

[ "15824848", "16355282", "15121405", "16418786", "16294137", "12510813", "15883638" ]

[ "Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study.", "Two-year clinical trial of oral alendronate versus intravenous pamidronate in children with osteogenesis imperfecta.", "Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study.", "Effects of oral alendronate on BMD in adult patients with osteogenesis imperfecta: a 3-year randomized placebo-controlled trial.", "Impact of alendronate on quality of life in children with osteogenesis imperfecta.", "Intravenous neridronate in adults with osteogenesis imperfecta.", "Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short-term functional improvement." ]

[ "In a randomized controlled study, we investigated the effect of treatment with intravenous neridronate in prepubertal children with OI. Our study suggests that quarterly intravenous infusions of the bisphosphonate significantly raise the rate of increase in BMD at both the spine and hip, the projected area of the lumbar vertebrae, and height. These results are associated with a significant decrease in the risk of clinical fractures.\n Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seem to be the most promising therapy, but randomized, controlled studies are scarce and have never been carried out in prepubertal children.\n This was a randomized, controlled 3-year clinical trial. The Italian Patients' Society of OI (AsItOI) sent their members affected by any type of OI to two centers at the University of Verona (Italy) to participate in the study. Sixty-four children, 6-11 years of age for boys and 6-9 years of age for girls, with no signs of puberty and who were never treated with bisphosphonates, were randomized to either intravenous neridronate (2 mg/kg infused IV in 30 minutes every 3 months) or no treatment, with a ratio of 2:1. Control patients were given the same bisphosphonate therapy at the end of the first year. BMD and projected bone areas, as measured by DXA, at spine and hip, height, and peripheral fracture incidence, both prospective and retrospective (2 years preceding randomization), were the main outcomes of the study.\n At the end of the first year, spine and hip BMD rose by 3.5-5.7% in control patients and by 18-25% (p < 0.001 versus controls) in the active group, respectively. During the following 2 years, the treatment in all patients was associated with BMD increases of 10-25% per year. Height and the DXA-derived projected area of lumbar spine rose during the first year of observation significantly more in the active group than in the control group (<0.01 and <0.05, respectively). Both height and spine projected area continued to rise in the treated patients toward levels found in healthy individuals. During the first year of treatment, 45% of the control patients and 27% of the active group had a nonvertebral fracture, but this difference was not statistically significant (p = 0.2). The total number of fractures was 18 in the 22 control patients and 13 in the active group (relative risk, 0.36; 95% CI, 0.15-0.87; p < 0.05).\n Intravenous neridronate infusions, administered quarterly, significantly increase BMD and lower the risk of clinical fracture in prepubertal children with OI.", "A 2-year prospective, partially randomized open-label trial comparing oral alendronate with intravenous pamidronate therapy in children with OI showed equivalence in increasing total body BMD, spine BMD, and linear growth, and decreasing bone turnover and fracture incidence. Children with mild OI had greater responses than severe OI in BMD and growth.\n Bisphosphonate therapies increase BMD and may reduce fractures in children with osteogenesis imperfecta (OI). A study directly comparing oral with intravenous bisphosphonate has not been published. This clinical trial compares oral alendronate with intravenous pamidronate in children with OI using an open-label, prospective, 2-year, randomized design.\n Children over the age of 3 years were stratified by bone age, pubertal stage, and type of OI and then randomized to receive oral alendronate 1 mg/kg/day in tablet form or intravenous pamidronate, 3 mg/kg/4 months. One child was assigned to pamidronate. One child randomized to intravenous pamidronate changed to oral alendronate. Eighteen children completed 12 months of therapy: nine on oral alendronate and nine on intravenous pamidronate. Primary outcome efficacy was increase in BMD. Secondary outcomes included changes in bone turnover biomarkers, fracture incidence, and growth.\n Total body and lumbar spine BMD increased, turnover markers decreased, and linear growth increased equivalently with oral and intravenous therapy. Fracture incidence showed a trend to decrease in both groups, with a significant decrease in fracture rates when the oral and intravenous groups were pooled. There were greater responses in BMD and growth in children with milder OI (type I) than those with more severe disease (types III and IV), but there were no significant effects of age or pubertal stage.\n Oral and intravenous bisphosphonate therapies are equally effective in children with OI and are particularly effective in milder forms. The oral route is highly acceptable in children and has practical advantages over the intravenous route.", "Non-randomised studies have suggested beneficial effects of bisphosphonates in osteogenesis imperfecta. We assessed the effects of oral olpadronate in children with this disorder in a randomised double-blind placebo-controlled trial.\n 34 children recruited from the Dutch national centre for osteogenesis imperfecta were randomly assigned olpadronate (10 mg/m2 daily; n=16) or placebo (n=18) for 2 years. All children also received calcium and vitamin D supplements. Primary endpoints were incident fractures of long bones and changes in bone mineral content (BMC), bone mineral density (BMD), and functional outcome. Anthropometry, vertebral height, and urinary markers of bone resorption were also studied. Analyses were by intention to treat.\n Fracture follow-up was complete for all the children, including two who withdrew from the study (one from each group). Olpadronate treatment was associated with a 31% reduction in relative risk of fracture of long bones (hazard ratio 0.69 [95% CI 0.52-0.91], p=0.01). The olpadronate group showed significantly greater increases than the placebo group in spinal BMC (difference between groups 2.24 g/year [0.20-4.29], p=0.03) and spinal BMD (difference between groups 0.054 g/cm2 per year [0.012-0.096], p=0.01). There were no detectable effects on functional outcome, anthropometrics, or vertebral height and no differences between the groups in changes in urinary markers of bone resorption.\n Oral treatment with olpadronate at a daily dose of 10 mg/m2 results in a reduction of fracture risk of long bones in children with osteogenesis imperfecta. However, the issue of whether bisphosphonates will alter the natural course of osteogenesis imperfecta remains unresolved, and further studies are needed.", "A 3-year, randomized, double-blind, placebo-controlled trial evaluated the effect of oral alendronate on the BMD of 64 adult patients with osteogenesis imperfecta. The mean increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/- 5.7% in the alendronate and placebo groups, respectively. Oral alendronate increases BMD in adult patients with osteogenesis imperfecta.\n This study evaluated the effect of oral alendronate on the BMD of adult patients with osteogenesis imperfecta.\n We carried out a 3-year, randomized, double-blind, placebo-controlled trial of oral alendronate in 64 adult patients with osteogenesis imperfecta. The primary endpoint was the difference between the groups in the mean percent change in lumbar spine BMD at 3 years. Secondary outcomes included changes in BMD of total hip, vertebral and peripheral fracture incidence, pain, hearing loss, and bone turnover biochemical markers. Patients were treated daily with either placebo or 10 mg alendronate. All received 1 g of calcium and 800 IU of vitamin D daily.\n The mean +/- SD increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/- 5.7% in the alendronate and placebo groups, respectively. Hip BMD increased in the alendronate group by 3.3 +/- 0.5% (p = 0.001) and decreased in the placebo group by 0.3 +/- 0.6%. The sample size was not sufficient to determine an effect of alendronate on fracture rate. A significant increase of the pain score was noted in the alendronate group (p = 0.04) in the intent-to-treat analysis but not in the per protocol analysis. There was no change in hearing in either group. Bone resorption and formation biochemical markers were significantly decreased in the alendronate group (p < 0.001). There were no differences in severe adverse effects between the groups, but there was an increase in nonsevere upper gastrointestinal effects in the alendronate group (p = 0.003).\n Oral alendronate increases BMD and increase nonsevere gastrointestinal adverse effects but does not modify the hearing loss in adult patients with osteogenesis imperfecta. More studies are needed to evaluate an effect on the fracture rate.", "Osteogenesis imperfecta (OI) is a debilitating clinical condition characterized by fragile bone and skeletal deformity. Over the past decade frequent reports have suggested that the cyclical administration of intravenous pamidronate has a positive impact on bone density and skeletal fractures; however, the impact of such therapy on the quality of life (QOL) has rarely been reported. Alendronate, an oral bisphosphonate, is widely used to treat osteoporosis. The purpose of this study was to evaluate the impact of daily alendronate on QOL and bone parameters in children with OI. A prospective double-blind crossover study was designed in which placebo was alternated with daily alendronate. Twenty children with types I, III, and IV OI were recruited. Seventeen patients completed the study. Markers of QOL were measured in children with type III and IV OI (n = 15) using total mobility (PEDI), self-care (WeeFIM), well-being, pain, and use of analgesic scores. After 1 year of alendronate therapy, vertebral bone mineral density (BMD) improved from a change in standard deviation score (z-score) of 0.89 +/- 0.19 to -0.12 +/- 0.14 after 1 year of placebo (P < 0.001). All QOL markers, except for mobility score, improved in response to alendronate therapy. Change in height z-score also improved in response to 1 year of alendronate therapy (0.41 +/- 0.21 vs. -0.09 +/- 0.11, P < 0.05). Alendronate therapy did not alter serum levels of calcium, osteocalcin, parathyroid hormone (PTH), 1, 5 (OH)2 vitamin D, cholesterol, or urinary hydroxyproline or any other biochemical marker evaluated. Alendronate decreased by 56% urinary cross-linked N-telopeptide of type 1 collagen divided by urinary creatinine (uNTX/uCr). Daily alendronate therapy was well tolerated. Only two patients had mild gastrointestinal discomfort, responding to minor adjustments in alendronate intake. Daily alendronate therapy is safe and effective in improving QOL in children with OI.", "Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seems to be the most promising therapy, at least in children. We tested IV neridronate, an amino-bisphosphonate structurally similar to alendronate and pamidronate in adults with OI. Twenty-three men and 23 premenopausal women with OI were randomized to either iv neridronate (100 mg infused intravenously for 30 minutes every 3 months) or no treatment with a ratio of 2 to 1. Control patients were given the same bisphosphonate therapy at the end of the first year. Clinical evaluation included bone densitometry measurements using dual energy X-ray absorptiometry (DXA), fasting serum and urinary biochemistry every 6 months, and radiographs of the spine taken at baseline and after 12 and 24 months of follow-up. Spine and hip bone mineral density rose by 3.0 +/- 4.6% (SD) and by 4.3 +/- 3.9%, respectively, within the first 12 months of treatment, whereas small insignificant changes were observed in the control group. During the second year of follow-up, additional 3.91% and 1.49% increases were observed at the spine and hip, respectively. Markers of skeletal turnover significantly fell during neridronate treatment. Fracture incidence during neridronate treatment was significantly lower than before therapy and compared with controls. Neridronate iv infusions, administered quarterly, significantly increase bone mineral density and lowered the risk of clinical fracture in adults with OI. Bisphosphonate therapy seems to provide clinical benefits, not only to children with OI, but also to adult patients.", "Bisphosphonates have been widely administered to children with OI based on observational trials. A randomized controlled trial of q3m intravenous pamidronate in children with types III and IV OI yielded positive vertebral changes in DXA and geometry after 1 year of treatment, but no further significant improvement during extended treatment. The treated group did not experience significantly decreased pain or long bone fractures or have increased motor function or muscle strength.\n Bisphosphonates, antiresorptive drugs for osteoporosis, are widely administered to children with osteogenesis imperfecta (OI). Uncontrolled pamidronate trials in OI reported increased BMD, vertebral coronal area, and mobility, and decreased pain. We conducted a randomized controlled trial of pamidronate in children with types III and IV OI.\n This randomized trial included 18 children (4-13 years of age) with types III and IV OI. The first study year was controlled; 9 children received pamidronate (10 mg/m2/day IV for 3 days every 3 months). Four children in each group also received recombinant growth hormone (rGH) injections (0.06 mg/kg/day for 6 days/week). Seven children in the treatment group received pamidronate for an additional 6-21 months. All patients had L1-L4 DXA, spine QCT, spine radiographs, and musculoskeletal and functional testing.\n In the controlled phase, treated patients experienced a significant increase in L1-L4 DXA z score (p < 0.001) and increased L1-L4 mid-vertebral height (p = 0.014) and total vertebral area (p = 0.003) compared with controls. During extended treatment, DXA z scores and vertebral heights and areas did not increase significantly beyond the 12-month values. Fracture rate decreased significantly in the upper extremities (p = 0.04) but not the lower extremities (p = 0.09) during the first year of treatment. Gross motor function, muscle strength, and pain did not change significantly during the controlled or extended treatment phases.\n A controlled trial confirmed the spine benefits of short-term pamidronate treatment in children with types III and IV OI. Pamidronate increased L1-L4 vertebral DXA and decreased vertebral compressions and upper extremity fractures. Vertebral measures did not improve during the extended treatment phase. The treatment group did not experience decreased lower extremity long bone fractures, significant improvement in growth, ambulation, muscle strength, or pain. There was substantial variability in individual response to treatment." ]

[ "12814710", "10801253", "8264145", "8591712", "9405913", "12138263", "10574417", "15364796", "15695126", "15462110", "11981066", "8243858", "12602538", "7489845", "12105140", "15754269", "16303728", "1521727", "12612979", "1747221", "15492322", "16253600", "16014056", "8905205", "11682660", "11358679" ]

[ "MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial.", "Effect of fluvastatin on proteinuria in patients with immunoglobulin A nephropathy.", "Simvastatin therapy for hypercholesterolemic patients with nephrotic syndrome or significant proteinuria.", "Effects of pravastatin on lipid levels, in vitro oxidizability of non-HDL lipoproteins and microalbuminuria in IDDM patients.", "Reduction of albumin excretion rate in normotensive microalbuminuric type 2 diabetic patients during long-term simvastatin treatment.", "Impact of treatment of dyslipidemia on renal function, fat deposits and scarring in patients with persistent nephrotic syndrome.", "The effect of pravastatin on renal function and lipid metabolism in patients with renal dysfunction with hypertension and hyperlipidemia. Pravastatin and Renal Function Research Group.", "Effect of pravastatin on cardiovascular events in people with chronic kidney disease.", "Long-term fluvastatin reduces the hazardous effect of renal impairment on four-year atherosclerotic outcomes (a LIPS substudy).", "Safety and efficacy of fluvastatin in hyperlipidemic patients with chronic renal disease.", "Effect of cerivastatin on proteinuria and urinary podocytes in patients with chronic glomerulonephritis.", "Renal function and insulin sensitivity during simvastatin treatment in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria.", "Atorvastatin improves metabolic control and endothelial function in type 2 diabetic patients: a placebo-controlled study.", "Cholesterol-lowering therapy may retard the progression of diabetic nephropathy.", "Effect of pravastatin on proteinuria in patients with well-controlled hypertension.", "First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease.", "Safety and efficacy of atorvastatin in patients with severe renal dysfunction.", "Plasma lipoproteins and renal function during simvastatin treatment in diabetic nephropathy.", "A controlled, prospective study of the effects of atorvastatin on proteinuria and progression of kidney disease.", "Associated effect of hepatic hydroxymethylglutaryl coenzyme A reductase + angiotensin converting enzyme inhibitors on the progression of renal failure in hypertensive subjects.", "Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria.", "Effect of rosuvastatin on C-reactive protein and renal function in patients with chronic kidney disease.", "Add-on and withdrawal effect of pravastatin on proteinuria in hypertensive patients treated with AT receptor blockers.", "A prospective clinical trial comparing the treatment of idiopathic membranous nephropathy and nephrotic syndrome with simvastatin and diet, versus diet alone.", "Effect of simvastatin on renal function in autosomal dominant polycystic kidney disease.", "Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes." ]

[ "Individuals with diabetes are at increased risk of cardiovascular morbidity and mortality, although typically their plasma concentrations of LDL cholesterol are similar to those in the general population. Previous evidence about the effects of lowering cholesterol in people with diabetes has been limited, and most diabetic patients do not currently receive cholesterol-lowering therapy despite their increased risk.\n 5963 UK adults (aged 40-80 years) known to have diabetes, and an additional 14573 with occlusive arterial disease (but no diagnosed diabetes), were randomly allocated to receive 40 mg simvastatin daily or matching placebo. Prespecified analyses in these prior disease subcategories, and other relevant subcategories, were of first major coronary event (ie, non-fatal myocardial infarction or coronary death) and of first major vascular event (ie, major coronary event, stroke or revascularisation). Analyses were also conducted of subsequent vascular events during the scheduled treatment period. Comparisons are of all simvastatin-allocated versus all placebo-allocated participants (ie, intention to treat), which yielded an average difference in LDL cholesterol of 1.0 mmol/L (39 mg/dL) during the 5-year treatment period.\n Both among the participants who presented with diabetes and among those who did not, there were highly significant reductions of about a quarter in the first event rate for major coronary events, for strokes, and for revascularisations. For the first occurrence of any of these major vascular events among participants with diabetes, there was a definite 22% (95% CI 13-30) reduction in the event rate (601 [20.2%] simvastatin-allocated vs 748 [25.1%] placebo-allocated, p<0.0001), which was similar to that among the other high-risk individuals studied. There were also highly significant reductions of 33% (95% CI 17-46, p=0.0003) among the 2912 diabetic participants who did not have any diagnosed occlusive arterial disease at entry, and of 27% (95% CI 13-40, p=0.0007) among the 2426 diabetic participants whose pretreatment LDL cholesterol concentration was below 3.0 mmol/L (116 mg/dL). The proportional reduction in risk was also about a quarter among various other subcategories of diabetic patient studied, including: those with different duration, type, or control of diabetes; those aged over 65 years at entry or with hypertension; and those with total cholesterol below 5.0 mmol/L (193 mg/dL). In addition, among participants who had a first major vascular event following randomisation, allocation to simvastatin reduced the rate of subsequent events during the scheduled treatment period.\n The present study provides direct evidence that cholesterol-lowering therapy is beneficial for people with diabetes even if they do not already have manifest coronary disease or high cholesterol concentrations. Allocation to 40 mg simvastatin daily reduced the rate of first major vascular events by about a quarter in a wide range of diabetic patients studied. After making allowance for non-compliance, actual use of this statin regimen would probably reduce these rates by about a third. For example, among the type of diabetic patient studied without occlusive arterial disease, 5 years of treatment would be expected to prevent about 45 people per 1000 from having at least one major vascular event (and, among these 45 people, to prevent about 70 first or subsequent events during this treatment period). Statin therapy should now be considered routinely for all diabetic patients at sufficiently high risk of major vascular events, irrespective of their initial cholesterol concentrations.", "3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are established drugs for the treatment of hypercholesterolemia, but several studies have shown that benefits obtained with these drugs are not causally related only to regression of cholesterol lowering. Moreover, in experimental models of progressive renal disease, statins have reduced the extent of glomerulosclerosis. This study evaluated the antiproteinuric effect of a daily dose of 40 mg fluvastatin for 6 months in moderately proteinuric patients with immunoglobulin A nephropathy, stable renal function, and no indicators of poor long-term prognosis. The effects of therapy were evaluated on the basis of 24-hour proteinuria (total proteinuria and albuminuria), albuminemia, creatinine clearance, cholesterol, and triglyceride values. Renal function remained stable in all patients. A significant decrease in proteinuria was observed after 6 months of therapy and persisted for all the observations. An increase in serum albumin was observed after 6 months of therapy. This study suggests that there is an antiproteinuric effect of HMG-CoA reductase inhibitors in moderately proteinuric patients with immunoglobulin A nephropathy.", "Experimental evidence suggests that lipid lowering therapy could slow the progression of renal disease in humans. We have conducted a double-blind, placebo controlled trial of the HMG CoA reductase inhibitor simvastatin in patients with the nephrotic syndrome or significant proteinuria (> 1 g/day) and hypercholesterolemia (> or = 6.5 mmol/liter). Patients were placed on a lipid lowering diet for at least 10 weeks before randomization. After a four-week placebo run-in, 30 adults were randomized to simvastatin or placebo therapy (10 mg/day, increasing to 20 to 40 mg/day as required) for 24 weeks. There were seven dropouts, none of whom were \"definitely\" related to drug therapy. Total and LDL cholesterol levels fell by a mean of 33 and 31%, respectively, in simvastatin treated patients, compared with only 5 and 1% in patients on placebo (P < 0.001, P = 0.002, respectively). Apolipoprotein B100 levels fell by a mean of 31% in the simvastatin group but rose 0.3% in the placebo group (P = 0.014). There were no significant changes in HDL levels. There were no significant differences between the groups in their urine protein levels, their rise in plasma creatinine, or decline in plasma inulin clearance. Simvastatin is a safe, effective therapy for hypercholesterolemia in proteinuric states. A much larger trial is needed to show if potent lipid-lowering therapy slows progression of hypercholesterolemic proteinuric diseases.", "The effects of pravastatin on plasma lipid levels, in vitro oxidizability of the non-HDL fraction, metabolic control, urinary albumin excretion, and four serum enzymes (SGPT, SGOT, GT and CPK) were studied in 20 insulin-dependent diabetic patients (IDDM) with incipient nephropathy. The patients were divided into two groups and the study was carried out by a crossover design. After 12 weeks pravastatin treatment (20 mg daily), plasma cholesterol, LDL-cholesterol and apolipoprotein B (Apo B) decreased by 22, 19 and 15%, respectively. The thiobarbituric acid reactive substances (TBARS) formation and the oxidation lagtime of the non-HDL fraction during the in vitro incubation with copper were not changed before and after treatment. The HbA1c and blood glucose levels, urinary albumin excretion, SGOT, SGPT and GT were not influenced by pravastatin treatment. CPK activity was elevated after 12 weeks of pravastatin treatment, and this elevation persisted even after the 12 weeks placebo period. So, pravastatin could be used as an effective drug for IDDM patients with incipient nephropathy, but close monitoring of the CPK activity is recommended.", "To study the long-term effects of simvastatin on urinary albumin excretion rate (AER) in normotensive microalbuminuric type 2 diabetic patients with hypercholesterolemia.\n A total of 19 normotensive microalbuminuric hypercholesterolemic type 2 diabetic patients entered a double-blind crossover study for 2 years, receiving either simvastatin (20 mg/day) or placebo (each treatment for 1 year).\n Simvastatin significantly decreased plasma cholesterol (total and LDL) after 52 weeks of treatment. A concomitant significant decrease of AER (25% from basal) with no significant changes in creatinine clearance was observed during the same period.\n Our data are in keeping with the hypothesis that simvastatin might be used as an additional means to preserve renal function in microalbuminuric hypercholesterolemic type 2 diabetic patients.", "In this study 43 patients with idiopathic nephrotic syndrome were randomly distributed into 2 age- and sex-matched groups. The first group was given fluvastatin while the second was used as control. The cases in the 2 groups were evaluated clinically, biochemically (creatinine clearance, albumin, 24-hour proteinuria, and lipogram), neurologically, and histopathologically (examination of renal biopsies obtained basally and after 1 year of treatment with fluvastatin). In the fluvastatin-treated group but not in the control group, we observed a significant reduction in cholesterol, low-density lipoprotein, and triglyceride. Clinical and laboratory assessment showed satisfactory tolerance of the drug by the patients. Proteinuria, serum albumin and creatinine clearance values were significantly better in the statin-treated patients. There was no difference in glomerular sclerosis between the 2 groups while interstitial fibrosis and renal fat deposits were less in the statin-treated group. The reduction in renal fat deposits in the statin-treated group was highly significant, while that of interstitial fibrosis was not. We conclude that: (1) statin can be safely and effectively used in the treatment of dyslipidemia in patients with persistent idiopathic nephrotic syndrome; (2) control of dyslipidemia in nephrotic patients is associated with better control of proteinuria and creatinine clearance; (3) statin treatment may cause regression of renal fat deposits in patients with nephrotic syndrome, and (4) longer term studies are still required to study further possible beneficial effects on renal histology and disease progression.\n Copyright 2002 S. Karger AG, Basel", "The effect of pravastatin on renal function in hypertensive patients with mild renal dysfunction and hyperlipidemia was examined. A total of 57 subjects given dihydropyridine calcium blockers were randomly assigned to placebo (n = 25) and pravastatin groups (n = 32). The period of study was 6 months. In the placebo group, lipid metabolism did not change throughout the study period, but the serum creatinine concentration (Scr) increased from a baseline of 1.6+/-0.07 mg/dl to 2.1+/-0.2 mg/dl in the 6th month of study and blood urea nitrogen (BUN) increased from 26.2+/-1.1 mg/dl to 32.4+/-30.1 mg/dl. In the pravastatin group, the serum total cholesterol decreased from a baseline of 251.4+/-7.3 mg/dl to 218.2+/-6.5 mg/dl in the 6th month of study, while Scr (1.3+/-0.07 mg/dl vs. 1.3 +/-0.09 mg/dl) and BNU (20.5+/-1.2 mg/dl vs. 21.0+/-1.4 mg/dl) did not change. The change in Scr in the placebo group was significantly different from that in the pravastatin group (F = 3.75, p = 0.05). The slope of the change in 1/Scr was 0.02+/-0.07 dl x mg(-1) x month(-1) in placebo group and -0.01+/-0.03 dl x mg(-1) month(-1) in pravastatin group (P<0.05). The results indicate that pravastatin attenuates the deterioration of renal function in patients with mild renal dysfunction, together with an improvement of lipid metabolism.", "Limited data describe the cardiovascular benefit of HMG-CoA reductase inhibitors (statins) in people with moderate chronic kidney disease (CKD). The objective of this analysis was to determine whether pravastatin reduced the incidence of cardiovascular events in people with or at high risk for coronary disease and with concomitant moderate CKD.\n We analyzed data from the Pravastatin Pooling Project (PPP), a subject-level database combining results from 3 randomized trials of pravastatin (40 mg daily) versus placebo. Of 19 700 subjects, 4491 (22.8%) had moderate CKD, defined by an estimated glomerular filtration rate of 30 to 59.99 mL/min per 1.73 m2 body surface area. The primary outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Moderate CKD was independently associated with an increased risk of the primary outcome (adjusted HR 1.26, 95% CI 1.07 to 1.49) compared with those with normal renal function. Among the 4491 subjects with moderate CKD, pravastatin significantly reduced the incidence of the primary outcome (HR 0.77, 95% CI 0.68 to 0.86), similar to the effect of pravastatin on the primary outcome in subjects with normal kidney function (HR 0.78, 95% CI 0.65 to 0.94). Pravastatin also appeared to reduce the total mortality rate in those with moderate CKD (adjusted HR 0.86, 95% CI 0.74 to 1.00, P=0.045).\n Pravastatin reduces cardiovascular event rates in people with or at risk for coronary disease and concomitant moderate CKD, many of whom have serum creatinine levels within the normal range. Given the high risk associated with CKD, the absolute benefit that resulted from use of pravastatin was greater than in those with normal renal function.", "Mild renal impairment is an important risk factor for late cardiovascular complications. This substudy of the Lescol Intervention Prevention Study (LIPS) assessed the effect of fluvastatin on outcome of patients who had renal dysfunction and those who did not. Complete data for creatinine clearance calculation (Cockcroft-Gault formula) were available for 1,558 patients (92.9% of the LIPS population). Patients were randomized to fluvastatin or placebo after successful completion of a first percutaneous coronary intervention. Follow-up time was 3 to 4 years. The effect of baseline creatinine clearance on coronary atherosclerotic events (cardiac death, nonfatal myocardial infarction, and coronary reinterventions not related to restenosis) was evaluated. Baseline creatinine clearance (logarithmic transformation) was inversely associated with an incidence of adverse events among patients who received placebo (hazard ratio 0.99, 95% confidence interval 0.982 to 0.998, p = 0.01). However, no association was noted between creatinine clearance and the incidence of adverse events among patients who received fluvastatin (hazard ratio 1.0, 95% confidence interval 0.99 to 1.0, p = 0.63). No further deterioration in creatinine clearance was observed during follow-up, regardless of baseline renal function or allocated treatment. Occurrence of adverse events was not related to changes in renal function during follow-up. Fluvastatin therapy markedly decreased the risk of coronary atherosclerotic events after percutaneous intervention in patients who had lower values of creatinine clearance at baseline. The benefit of fluvastatin was unrelated to any effect on renal function.", "There are few reports on the safety and efficacy of long-term treatment with statins in patients with chronic renal disease and hyperlipidemia. We evaluated these subjects treated with fluvastatin.\n After a 4-week run-in period, a total of 80 patients with diabetic nephropathy or chronic glomerulonephritis were randomly allocated to receive dietary therapy and fluvastatin 20 mg/day (n=39), or dietary therapy alone (n=41) for a period of 48 weeks. Lipid parameters, rhabdomyolysis-related indicators, 24-hour urinary albumin excretion and creatinine clearance were measured. The pharmacokinetics of fluvastatin was examined in 8 patients.\n Creatinine clearance and 24-hour urinary albumin excretion did not differ between the two groups. The peak serum fluvastatin concentration (Cmax) was 141+/-67 microg/L and the mean AUC0-6 h was 341+/-149 microgh/L. Fluvastatin treatment significantly lowered serum total cholesterol, low-density lipoprotein (LDL) cholesterol and apo-lipoprotein B concentrations by 16%, 25%, and 22%, respectively, compared with patients receiving dietary therapy alone. There were no significant differences in serum triglyceride and high-density lipoprotein (HDL) cholesterol concentrations between the two treatment groups. Serum creatine kinase and aldolase concentrations did not change throughout treatment in both groups.\n Fluvastatin treatment significantly improved lipid parameters in patients with chronic renal disease. Fluvastatin was well tolerated, with no adverse effects on renal function and no muscular toxicity. However, the drug showed no direct renoprotective effects.", "We previously reported urinary podocytes to be a marker of glomerular injury. The aim of the present study was to determine whether cerivastatin, a newly developed, potent synthetic statin, affects proteinuria and urinary podocyte excretion in patients with chronic glomerulonephritis (CGN).\n We randomly assigned 40 normotensive hypercholesterolemic patients with CGN to receive either cerivastatin 0.15 mg/day (n=20) or placebo (n=20). Subjects comprised 24 men and 16 women, with a mean age of 40.8+/-14.4 years; 27 had IgA nephropathy and 13 had non-IgA proliferative glomerulonephritis. Treatment was continued for 6 months. Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides, urinary protein excretion and the number of podocytes were measured before treatment and at 3 and 6 months after treatment.\n After 6 months, a significant reduction in total cholesterol (P<0.001), LDL-cholesterol (P<0.001) and triglycerides (P<0.05), and a significant increase in HDL-cholesterol (P<0.001) were observed in the group treated with cerivastatin. Urinary protein excretion decreased from 1.8+/-0.6 to 0.8+/-0.4 g/day, (P<0.01) in this group, and urinary podocyte excretion decreased from 1.6+/-0.6 to 0.9+/-0.4 cells/ml (P<0.01). However, placebo showed little effect on these lipid levels, urinary protein excretion and urinary podocyte excretion. The differences between the cerivastatin group and the placebo group were significant (cholesterol, P<0.001; LDL-cholesterol, P<0.001; triglycerides, P<0.05; HDL-cholesterol, P<0.001; urinary protein, P<0.01; and urinary podocytes, P<0.01).\n Statins such as cerivastatin may be beneficial for restoration of injured podocytes in patients with CGN and hypercholesterolaemia.", "The effect of simvastatin (10-20 mg/day) on kidney function, urinary albumin excretion rate and insulin sensitivity was evaluated in 18 Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria and moderate hypercholesterolaemia (total cholesterol > or = 5.5 mmol.l-1). In a double-blind, randomized and placebo-controlled design treatment with simvastatin (n = 8) for 36 weeks significantly reduced total cholesterol (6.7 +/- 0.3 vs 5.1 mmol.l-1 (p < 0.01)), LDL-cholesterol (4.4 +/- 0.3 vs 2.9 +/- 0.2 mmol.l-1 (p < 0.01)) and apolipoprotein B (1.05 +/- 0.04 vs 0.77 +/- 0.02 mmol.l-1 (p < 0.01)) levels as compared to placebo (n = 10). Both glomerular filtration rate (mean +/- SEM) (simvastatin: 96.6 +/- 8.0 vs 96.0 +/- 5.7 ml.min-1 x 1.73 m-2, placebo: 97.1 +/- 6.7 vs 88.8 +/- 6.0 ml.min-1 x 1.73 m-2)(NS) and urinary albumin excretion rate (geometric mean x/divided by antilog SEM) (simvastatin: 18.4 x/divided by 1.3 vs 16.2 x/divided by 1.2 microgram.min-1, placebo 33.1 x/divided by 1.3 vs 42.7 x/divided by 1.3 micrograms.min-1)(NS) were unchanged during the study. A euglycaemic hyperinsulinaemic clamp was performed at baseline and after 18 weeks in seven simvastatin- and nine placebo-treated patients. Isotopically determined basal and insulin-stimulated glucose disposal was similarly reduced before and during therapy in both the simvastatin (2.0 +/- 0.1 vs 1.9 +/- 0.1 (NS) and 3.1 +/- 0.6 vs 3.1 +/- 0.7 mg.kg-1 x min-1 (NS)) and the placebo group (1.9 +/- 0.1 vs 1.8 +/- 0.1 (NS) and 4.1 +/- 0.6 vs 3.8 +/- 0.2 mg.kg-1 x min-1 (NS)).(ABSTRACT TRUNCATED AT 250 WORDS)", "Several pieces of evidence support a role of inflammatory processes in the pathogenesis of atherosclerosis; it is also known that endothelial dysfunction is the initial lesion of the atherosclerotic process. Among other markers of endothelial dysfunction, some adhesion molecules seem to play an interesting role. The aim of the present study was to evaluate the effect of atorvastatin vs placebo on some indexes of leukocytes adhesion in a group of Type 2 diabetic patients. Twenty-five Type 2 diabetic patients free from microangiopathic complications and with LDL-cholesterol lower than 180 mg/dl were randomized to receive either atorvastatin (T2DA) or placebo (T2Dp) for twelve months. BMI, fasting plasma glucose, glycated hemoglobin (HbA1c), albumin excretion rate (AER), lipid profile, and serum concentrations of vascular cell adhesion molecule-1 (VCAM1), E-selectin and cadherin-5 were measured at baseline and at the end of the follow-up. At T0 E-selectin was 16 +/- 6 ng/ml in T2DA and 17 +/- 13 in T2Dp; VCAM1 was 413 +/- 112 ng/ml in T2DA and 411 +/- 112 in T2Dp. At T12 VCAM1 and E-selectin did not vary in T2Dp, while a significant reduction was observed in T2DA (VCAM1 275 +/- 104 ng/ml and E-selectin 8 +/- 3 ng/ml; p < 0.001 and p < 0.01, respectively). T2DA also showed a reduction of total and LDL cholesterol and an improved glycemic control respect to T2Dp. Hypolipidemic therapy was the strongest independent predictor of the cytokines variations along the time. These results confirm the role of statins in modulating endothelial function also in Type 2 diabetes, outlining a therapeutic role of these molecules probably independent from the hypolipidemic effect.", "There is experimental evidence to suggest that hypercholesterolaemia may play a pathogenetic role in progressive glomerular injury. We investigated the effect of cholesterol-lowering therapy on the progression of diabetic nephropathy in 34 patients with non-insulin-dependent diabetes mellitus. Patients were randomly assigned in a single-blind fashion to treatment with either lovastatin, an HMG CoA reductase inhibitor (n = 16; mean dose 30.0 +/- 12.6 mg/day) or placebo (n = 18) for 2 years. Renal function was assessed by serially measuring the serum creatinine, glomerular filtration rate (using Cr51-EDTA), and 24-h urinary protein excretion. Lovastatin treatment was associated with significant reductions in total cholesterol (p < 0.001), LDL-cholesterol (p < 0.001) and apo B (p < 0.01), the reductions at 24 months being 26, 30 and 18%, respectively. Beneficial effects on serum triglyceride, HDL-cholesterol and apo A1 levels were also observed. Lp(a) showed no significant change in both groups. Glomerular filtration rate deteriorated significantly in the placebo group after 24 months (p < 0.025) but showed no significant change in the lovastatin-treated patients. The increase in serum creatinine was statistically significant (p < 0.02) in placebo-treated patients at 12 and 24 months, and in the lovastatin group after 24 months. Twenty-four hour urinary protein excretion increased in both groups (p < 0.05). Lovastatin treatment was not associated with significant elevations in liver or muscle enzymes. We conclude that effective normalisation of hypercholesterolaemia may retard the progression of diabetic nephropathy.", "Proteinuria is an important risk factor for cardiovascular and renal morbidity and mortality. The effects of 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitor (statin) therapy on proteinuria in normolipidemic patients with well-controlled hypertension have not been studied. A total of 63 normolipidemic (total cholesterol <240 mg/dL) and proteinuric (300 to 3000 mg/d) patients with well-controlled blood pressure (<140/90 mm Hg) were randomized to receive either placebo (n=32) or pravastatin (10 mg/d; n=31) after a 3-month placebo period. Pravastatin lowered proteinuria after 6 months by 54% (P<0.0001). Creatinine clearance was stable throughout the study in the 2 groups. Despite unchanged plasma endothelin-1 levels throughout the study, urinary excretion of the peptide was decreased and significantly correlated with improvement in urinary protein excretion in pravastatin-treated patients (r=0.64, P=0.001). The urinary excretion of retinol-binding protein decreased after pravastatin administration, probably reflecting an improvement in tubular function. In contrast, the urinary excretion of IgG did not change significantly throughout the study in either group. Multivariate analysis revealed that proteinuria was only significantly correlated with statin use (P<0.0001, R2= 0.66). Linear regression analysis in the statin-treated group did not show any correlation between changes in lipid profiles and proteinuria regression. Thus, in addition to their primary function of antilipidemia, the addition of pravastatin to treatment for well-controlled hypertension may have an additive effect on reducing proteinuria independent of hemodynamics and lipid-lowering effects, possibly through inhibiting renal endothelin-1 synthesis and improving tubular function.", "Patients with chronic kidney disease are at increased risk for cardiovascular disease, but the efficacy and safety of simvastatin and aspirin are unknown in this patient group.\n Patients were randomly assigned in a 2 x 2 factorial design to the administration of: (1) 20 mg of simvastatin daily versus matching placebo, and (2) 100 mg of modified-release aspirin daily versus matching placebo.\n Overall, 448 patients with chronic kidney disease were randomly assigned (242 predialysis patients with a creatinine level > or = 1.7 mg/dL [> or =150 micromol/L], 73 patients on dialysis therapy, and 133 patients with a functioning transplant). Compliance with study treatments was 80% at 12 months. Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds (aspirin, 4 of 225 patients [2%] versus placebo, 6 of 223 patients [3%]; P = not significant [NS]), although there was a 3-fold excess of minor bleeds (34 of 225 [15%] versus 12 of 223 patients [5%]; P = 0.001). Among those with predialysis renal failure or a functioning transplant at baseline, aspirin did not increase the number of patients who progressed to dialysis therapy (7 of 187 [4%] versus 6 of 188 patients [3%]; P = NS) or experienced a greater than 20% increase in creatinine level (63 of 187 patients [34%] versus 56 of 188 patients [30%]; P = NS). After 12 months of follow-up, allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18% (simvastatin, 163 mg/dL [4.22 mmol/L] versus placebo, 196 mg/dL [5.08 mmol/L]; P < 0.0001), directly measured low-density lipoprotein cholesterol levels by 24% (89 mg/dL [2.31 mmol/L] versus 114 mg/dL [2.96 mmol/L]; P < 0.0001), and triglyceride levels by 13% (166 mg/dL [1.87 mmol/L] versus 186 mg/dL [2.10 mmol/L]; P < 0.01), but there was no significant effect on high-density lipoprotein cholesterol levels (2% increase; P = NS). Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels.\n During a 1-year treatment period, simvastatin, 20 mg/d, produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels, with no evidence of toxicity, and aspirin, 100 mg/d, did not substantially increase the risk for a major bleeding episode. Much larger trials are now needed to assess whether these treatments can prevent vascular events.", "To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a glomerular filtration rate of <30 ml/min.\n This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months.\n The follow-up period was a mean of 20+/-14.4 months (range 1-36 months) for those on atorvastatin versus 22+/-12.7 months (range 0.5-36 months) for the controls. Compared with baseline values, patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4 mmol/l; -23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; -35%; p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8 mmol/l). The controls had significantly reduced levels of total cholesterol at Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the controls, the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1-30. Fifteen patients (21%) stopped taking their medication as they could not tolerate the side-effects, the most frequent complaints being gastrointestinal discomfort and headache.\n Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.", "The aim of this study was to assess the effect of simvastatin on plasma lipoproteins and renal function in hypercholesterolaemic Type 1 (insulin-dependent) diabetic patients with diabetic nephropathy. Twenty-six hypercholesterolaemic (total cholesterol greater than or equal to 5.5 mmol/l) Type 1 diabetic patients with nephropathy were enrolled in a double-blind randomized placebo-controlled study for 12 weeks. The active treatment group (n = 14) received simvastatin (10-20 mg/day) for 12 weeks while the remaining 12 patients received treatment with placebo. The results during simvastatin treatment (baseline vs 12 weeks): total cholesterol 6.6 vs 4.8 mmol/l (p less than 0.01), LDL-cholesterol 4.25 vs 2.57 mmol/l (p less than 0.01) and apolipoprotein B 1.37 vs 1.06 mmol/l (p less than 0.01). HDL-cholesterol, and apolipoprotein A-I remained unchanged. Total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein A-I, apolipoprotein B remained unchanged during placebo treatment. Albuminuria measured during the simvastatin and the placebo treatment (baseline vs 12 weeks) (the data are logarithmically transformed before analysis because of their positively skewed transformation; geometric mean (x/divided by antilog SE) is indicated) was 458 (x/divided by 1.58) vs 393 (x/divided by 1.61) and 481 (x/divided by 1.62) vs 368 (x/divided by 1.78 micrograms/min (NS). Glomerular filtration rate during simvastatin and placebo treatment (baseline vs 12 weeks) was 64 vs 63 and 72 vs 74 ml.min-1.1.73 m-2, respectively. Two patients receiving simvastatin treatment were withdrawn, one due to gastrointestinal side effects and one due to myalgia.(ABSTRACT TRUNCATED AT 250 WORDS)", "Chronic kidney diseases, particularly if presenting with significant proteinuria, are commonly associated with substantial alteration of serum lipid levels. Experimental evidence suggests that lipid abnormalities may contribute to the progression of kidney disease. However, studies in humans on the subject are scarce.\n In a prospective, controlled open-label study, the authors have evaluated the effects of one-year treatment with atorvastatin, a 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitor, versus no treatment on proteinuria and progression of kidney disease in 56 patients with chronic kidney disease. Before randomization, all patients had already been treated for one year with angiotensin-converting enzyme (ACE) inhibitors or angiotensin AT1 receptor antagonists (ARBs) and other antihypertensive drugs.\n By the end of one-year treatment, urine protein excretion decreased from 2.2 +/- 0.1 to 1.2 +/- 1.0 g every 24 hours (P < 0.01) in patients treated with atorvastatin in addition to ACE inhibitor and ARBs. By contrast, urinary protein excretion decreased only from 2.0 +/- 0.1 to 1.8 +/- 0.1 g every 24 hours (P value not significant) in patients who did not receive atorvastatin in addition to ACE inhibitor or ARBs. During this time, creatinine clearance decreased only slightly and not significantly (from 51 +/- 1.8 to 49.8 +/- 1.7) in patients treated with atorvastatin. By contrast, during the same period of observation, creatinine clearance decreased from 50 +/- 1.9 to 44.2 +/- 1.6 mL/min (P < 0.01) in patients who did not receive atorvastatin.\n This study has shown that treatment with atorvastatin in addition to a regimen with ACE inhibitors or ARBs may reduce proteinuria and the rate of progression of kidney disease in patients with chronic kidney disease, proteinuria, and hypercholesterolemia. The benefits appear to occur in addition to those of treatment with ACE inhibitor and ARBs.\n Copyright 2003 by the National Kidney Foundation, Inc.", "nan", "Microalbuminuria is associated with increased risk of cardiovascular events. We assessed whether therapeutic intervention aimed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects (15 to 300 mg/24 hours).\n From the Prevention of Renal and Vascular Endstage Disease (PREVEND) cohort (n=8592), 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial (PREVEND IT). Of these subjects, 864 were randomized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo. The mean follow-up was 46 months, and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity. Mean age was 51+/-12 years; 65% of subjects were male, and 3.4% had a previous cardiovascular event. Mean cholesterol level was 5.8+/-1.0 mmol/L, mean systolic/diastolic blood pressure was 130+/-18/76+/-10 mm Hg, and median urinary albumin excretion was 22.8 (15.8 to 41.3) mg/24 hours. The primary end point occurred in 45 subjects (5.2%). Fosinopril reduced urinary albumin excretion by 26% (P<0.001). Subjects treated with fosinopril showed a 40% lower incidence of the primary end point (hazard ratio 0.60 [95% CI 0.33 to 1.10], P=0.098, log-rank). Pravastatin did not reduce urinary albumin excretion, and subjects treated with pravastatin showed a 13% lower incidence of the primary end point than subjects in the placebo group (0.87 [0.49 to 1.57], P=0.649, log-rank).\n In microalbuminuric subjects, treatment with fosinopril had a significant effect on urinary albumin excretion. In addition, fosinopril treatment was associated with a trend in reducing cardiovascular events. Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events.", "The purpose of this 20-week, open-label, randomized clinical trial was to evaluate the effect of rosuvastatin on fasting serum lipids and lipoproteins, high-sensitivity C-reactive protein (hs-CRP), and the glomerular filtration rate (GFR) in 91 patients with chronic kidney disease. Patients were randomized to rosuvastatin 10 mg/day (n = 48) or to no lipid-lowering treatment (n = 43) for 20 weeks. In contrast to patients not receiving rosuvastatin, patients receiving rosuvastatin tended to derive more favorable improvements from baseline values in low-density lipoprotein cholesterol (-43%, p <0.001, vs 7%, p = NS; p <0.001 for change with rosuvastatin treatment vs change with no antilipemic treatment), hs-CRP (-47%, p <0.001, vs 7%, p = NS; p <0.001 for change with rosuvastatin treatment vs change with no antilipemic treatment), and GFR (11%, p <0.05, vs 4%, p = NS; p = NS for change with rosuvastatin treatment vs change with no antilipemic treatment).", "Although angiotensin receptor antagonists and 3-hydroxy-3-methylgultaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to attenuate proteinuria individually, it remains unclear whether proteinuria may be additionally improved by statin therapy in well-controlled hypertensive patients treated with angiotensin receptor antagonists-based regimen and whether withdrawal of chronic statin treatment may abrogate this beneficial effect in normolipidemic patients.\n A total of consecutive 82 proteinuric patients treated with antihypertensive agents, including losartan, were randomized 10 mg of pravastatin or placebo with a 6-month treatment. After completing 6 months of drug treatment, the pravastatin-treated patients were randomly assigned to continue (N= 19) or withdraw (N= 17) pravastatin for a further 6 months.\n Subjects treated with pravastatin had significant further improvement of proteinuria at 6 months compared with placebo group (559 +/- 251 mg/24 hours vs. 1262 +/- 557 mg/24 hours) (P < 0.0001). Of 17 patients assigned to withdraw pravastatin, proteinuria returned to the pretreatment levels and was significantly higher than those who continued treatment. Multivariate analysis revealed that proteinuric improvement was significantly correlated with the continuous statin use. Urinary excretion of endothelin-1 (ET-1) is decreased in pravastatin-treated patients, but withdrawal of statin resulted in 27% up-regulation. The linear regression models in the initial statin-treated group showed that changes in urinary ET-1 correlated with urinary protein excretion (r= 0.83, P < 0.0001).\n We conclude that pravastatin administration is associated with improved proteinuria probably by inhibiting urine ET-1 levels in patients with losartan-based treatment. However, statin withdrawal abrogates this beneficial effect in patients initially responsive to this therapy.", "Of 17 patients with idiopathic membranous nephropathy (IMN) and nephrotic syndrome, 9 were allocated to treatment with simvastatin (an HMG CoA-reductase inhibitor) and low cholesterol diet, and 8 to diet alone. At entry, the treatment and control groups did not differ in mean serum creatinines, chromium-labelled EDTA clearances, urinary protein/creatinine ratios, serum albumins, and lipid profiles. The mean follow up period (+/- SEM) in the treated group was 19.3 (+/- 4.4) months compared with 16.6 (+/- 5.9) months in the control group. At the end of the trial the fall in chromium-labelled EDTA clearances was similar (-1.27 versus -1.28 mls/min/months/1.73 m2) in the treatment and control groups respectively. The mean (+/- SEM) total and LDL-cholesterol had gone from 10.5 (+/- 0.94) and 8.02 (+/- 1) mmol/l to 5.2 (+/- 0.49) and 3.47 (+/- 0.44) respectively in the treated patients. Additionally the mean (+/- SEM) albumin and urinary protein/creatinine ratio went from 25.6 (+/- 2.4) gm/l and 0.52 (+/- 0.09) gm/mmol to 45.5 (+/- 2.8) and 0.13 (+/- 0.04) respectively. There was little change in total and LDL-cholesterol; albumin and urinary protein/creatinine ratio in the control group. This study supports the observation that lowering serum cholesterol in the nephrotic syndrome reduces proteinuria and increases serum albumin levels. No difference in the rate of decline in renal function could be demonstrated.", "In animal models, HMG-CoA reductase inhibitors were able to improve renal function and endothelium-dependent vascular reactivity. In various experimental renal diseases, including autosomal dominant polycystic kidney disease (ADPKD), HMG-CoA reductase inhibitors improved the rate of decline in renal function. We studied the effect of simvastatin on ADPKD patients.\n In a double-blind cross-over study, 10 normocholesterolaemic ADPKD patients were treated in random order for 4 weeks with 40 mg simvastatin or placebo daily. After each treatment period, we investigated the effect of simvastatin on renal blood flow and endothelium-dependent vascular reactivity. These periods were separated by a 4-week wash-out period.\n After treatment with simvastatin, glomerular filtration rate (GFR) significantly increased from 124+/-4 ml/min to 132+/-6 ml/min (P<0.05). Simultaneously, effective renal plasma flow (ERPF) increased significantly from 494+/-30 ml/min to 619+/-67 ml/min after simvastatin treatment (P<0.05). These renal effects were accompanied by a significantly enhanced vasodilator response to acetylcholine in the forearm after simvastatin treatment. Total serum cholesterol levels were significantly reduced after treatment with simvastatin, from 4.24+/-0.32 to 3.17+/-0.22 mmol/l (P<0.001).\n We concluded that simvastatin treatment can ameliorate renal function in ADPKD patients, by increasing renal plasma flow, possibly via improvement of endothelial function. Long-term clinical trials with HMG-CoA reductase inhibitors are needed to confirm these results and to establish a chronic inhibiting effect of HMG-CoA reductase inhibitors on the progression towards end-stage renal disease in ADPKD patients.", "Although hyperlipidemia is associated with the development of diabetes complications, the effect of lipid reduction on microvascular complications is unknown. We initiated a 2-year, randomized, double-blinded placebo-controlled pilot trial of simvastatin/diet vs. diet alone in Type 1 diabetic patients without overt nephropathy. Thirty-nine patients with LDL cholesterol 100-160 mg/dl, >10 year duration of diabetes and an albumin excretion rate (AER) <200 microg/min were recruited for study. The primary end-point was change in AER. Secondary end-points were change in ankle-brachial index, progression of retinopathy status, change in vibratory threshold, and development of new clinical neuropathy. Nineteen patients were treated with simvastatin and twenty with placebo. However, because of the lowering of drug initiation levels by the American Diabetes Association, the trial was terminated early with 2 subjects reaching 2 years, 17 reaching 18 months, 36 reaching 1 year, and all 6 months. Simvastatin significantly reduced total cholesterol (mean on treatment 173.4 vs. 191.4, P=.020) and LDL cholesterol (mean on treatment 105.0 vs. 127.7, P<.001). Simvastatin therapy was associated with a slower rise in AER compared to placebo, though the result was not statistically significant (median rate of change/month 0.004 vs. 0.029). There was a trend towards slower progression of neuropathy as measured by vibratory threshold (median change at 1 year 0.03 simvastatin vs. 0.94, P=.07). There was no difference in change in ankle-brachial index, clinical neuropathy status, or retinopathy status. In conclusion, treatment with simvastatin may have a beneficial effect on early nephropathy and diabetic neuropathy, justifying a fully powered trial. However, this would be difficult under current treatment guidelines." ]

[ "21508145", "17284630", "18302514", "16837619" ]

[ "The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto's thyroiditis.", "The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies.", "No immunological benefit of selenium in consecutive patients with autoimmune thyroiditis.", "Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses." ]

[ "No previous study determined monocyte- and lymphocyte-suppressing effects of levothyroxine and selenomethionine and assessed whether their coadministration is superior to treatment with only one of these drugs.\n Our objective was to compare the effect of levothyroxine and selenomethionine on monocyte and lymphocyte cytokine release and systemic inflammation in patients with Hashimoto's thyroiditis. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: We conducted a randomized clinical trial involving a group of 170 ambulatory euthyroid women with recently diagnosed and previously untreated Hashimoto's thyroiditis and 41 matched healthy subjects. Participants were randomized in a double-blind fashion to receive a 6-month treatment with levothyroxine, selenomethionine, levothyroxine plus selenomethionine, or placebo. One hundred sixty-five patients completed the study.\n Monocyte and lymphocyte release of proinflammatory cytokines and plasma levels of C-reactive protein (CRP) were assessed.\n Compared with the control subjects, monocytes and lymphocytes of Hashimoto's thyroiditis patients released greater amounts of all cytokines studied. Levothyroxine reduced monocyte release of TNF-α, IL-1β, IL-6, and monocyte chemoattractant protein-1, whereas selenomethionine inhibited lymphocyte release of IL-2, interferon-γ, and TNF-α, which was accompanied by a reduction in plasma CRP levels. The decrease in cytokine release and in plasma CRP levels was strongest when both drugs were given together.\n Despite affecting different types of inflammatory cells, levothyroxine and selenomethionine exhibit a similar systemic antiinflammatory effect in euthyroid females with Hashimoto's thyroiditis. This action, which correlates with a reduction in thyroid peroxidase antibody titers, may be associated with clinical benefits in the prevention and management of Hashimoto's thyroiditis, particularly in subjects receiving both agents.", "Pregnant women who are positive for thyroid peroxidase antibodies [TPOAb(+)] are prone to develop postpartum thyroid dysfunction (PPTD) and permanent hypothyroidism. Selenium (Se) decreases thyroid inflammatory activity in patients with autoimmune thyroiditis.\n We examined whether Se supplementation, during and after pregnancy, influences the thyroidal autoimmune pattern and function.\n This was a prospective, randomized, placebo-controlled study.\n The study was conducted in the Department of Obstetrics and Gynecology and Department of Endocrinology.\n A total of 2143 euthyroid pregnant women participated in the study; 7.9% were TPOAb(+).\n During pregnancy and the postpartum period, 77 TPOAb(+) women received selenomethionine 200 microg/d (group S1), 74 TPOAb(+) women received placebo (group S0), and 81 TPOAb(-) age-matched women were the control group (group C).\n We measured the prevalence of PPTD and hypothyroidism.\n PPTD and permanent hypothyroidism were significantly lower in group S1 compared with S0 (28.6 vs. 48.6%, P<0.01; and 11.7 vs. 20.3%, P<0.01).\n Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism.", "Recently it has been demonstrated that after selenium (Se) supplementation in autoimmune thyroiditis (AIT) patients, there was a significant decrease of thyroid peroxidase (TPO) autoantibody (TPOAb) levels. The aim of our study was to evaluate the immunological benefit of Se administration in unselected AIT patients and thus address the question whether Se administration should generally be recommended for AIT patients.\n Thirty-six consecutive AIT patients (aged 19-85 years) were included in the present study. In addition to their levothyroxine (LT(4)) treatment, 18 patients received 200 microg (2.53 micromol) sodium selenite per day orally for the time span of 3 months, whereas 18 patients received placebo. All patients had measurement of thyroid hormones, thyrotropin (TSH), autoantibodies (thyroglobulin antibodies [TgAb] and TPOAb), Se levels, and intracellular cytokine detection in CD4(+) and CD8(+) T cells of peripheral blood mononuclear cells (PBMC) by flow cytometry before and after Se or placebo administration.\n No significant difference in the TPOAb levels was found after Se administration (524 +/- 452 vs. 505 +/- 464 IU/mL; p > 0.05). Furthermore, we found no significant differences in the CD4(+) or CD8(+) cytokine pattern (IFN-gamma, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-alpha, TNF-beta) in patients before and after Se administration, in patients before and after placebo administration and between Se group and placebo group before and after Se vs. placebo administration.\n We demonstrate that Se administration in our AIT patient's cohort does not induce significant immunological changes, either in terms of cytokine production patterns of peripheral T lymphocytes or of TPOAb levels. Our data suggest that AIT patients with moderate disease activity (in terms of TPOAb and cytokine production patterns) may not (equally) benefit as patients with high disease activity.", "The aim of this study is to investigate the long-term (9 months) effects of variable doses (200/100 microg/day) of L-selenomethionine on autoimmune thyroiditis (AIT) and the parameters affecting the success rate of this therapy. The present study was designed in three steps: (1) 88 female patients with AIT (mean age = 40.1 +/- 13.3 years) were randomized into two groups according to their initial serum TSH, thyroid peroxidase antibody (TPOAb) concentrations, and age. All the patients were receiving L-thyroxine to keep serum TSH <or=2 mIU/l. Group S2 (n = 48, mean TPOAb = 803.9 +/- 483.8 IU/ml) received 200 microg L-selenomethionine per day, orally for 3 months, and group C (n = 40, mean TPOAb = 770.3 +/- 406.2 IU/ml) received placebo. (2) 40 volunteers of group S2 were randomized into two age- and TPOAb-matched groups. Group S22 (n = 20) went on taking L-selenomethionine 200 microg/day, while others (group S21) lowered the dose to 100 microg/day. (3) 12 patients of group S22 (group S222) went on taking L-selenomethionine 200 microg/day, while 12 patients of group S21 (S212) increased the dose to 200 microg/day. Serum titers of TPOAb decreased significantly in group S2 (26.2%, P < 0.001), group S22 (23.7%, P < 0.01) and group S212 (30.3%, P < 0.01). There were no significant changes in group C and group S222 (P > 0.05). TPOAb titers increased significantly in group S21 (38.1%, P < 0.01). A significant decrease in thyroglobulin antibody titers was only noted in group S2 (5.2%, P < 0.01). L-selenomethionine substitution suppresses serum concentrations of TPOAb in patients with AIT, but suppression requires doses higher than 100 microg/day which is sufficient to maximize glutathione peroxidase activities. The suppression rate decreases with time." ]

[ "7605179", "15326246", "16942454", "1300186", "17361345" ]

[ "Strength training in patients with myotonic dystrophy and hereditary motor and sensory neuropathy: a randomized clinical trial.", "Strength training and albuterol in facioscapulohumeral muscular dystrophy.", "Night splinting does not increase ankle range of motion in people with Charcot-Marie-Tooth disease: a randomised, cross-over trial.", "A randomized controlled trial of early surgery in Duchenne muscular dystrophy.", "Effects of training and albuterol on pain and fatigue in facioscapulohumeral muscular dystrophy." ]

[ "A randomized clinical trial on the effects of strength training was performed in myotonic dystrophy (MyD) patients and patients with hereditary motor and sensory neuropathy (HMSN). Training and most measurement tools involved the proximal lower extremity muscles. The participants trained 3 times a week for 24 weeks with weights adapted to their force. Strength was evaluated by isokinetically measured knee torque. Fatiguability was assessed by the time an isometric contraction could be sustained. Functional performance was measured by timed motor performance and by questionnaires on functional performance. Serum myoglobin (Mb) levels were determined to detect changes in muscle fiber membrane permeability. The MyD group included 33 participants, and the HMSN group included 29 participants. Within each diagnostic group, patients were individually matched and subsequently randomized for treatment allocation. In the MyD patients, none of the measurement techniques showed any training effect. Neither were there signs of deterioration caused by the training. In the HMSN group, knee torques increased. Timed motor performance did not change, although the questionnaires showed an improvement on items related to upper-leg function. Mb levels did not change significantly as a result of the training. In conclusion, the MyD group showed neither positive nor negative effects of the training protocol, whereas the training produced a moderate increase in strength and leg-related functional performance in the HMSN group.", "In animals and healthy volunteers beta2-adrenergic agonists increase muscle strength and mass, in particular when combined with strength training. In patients with facioscapulohumeral muscular dystrophy (FSHD) albuterol may exert anabolic effects. The authors evaluated the effect of strength training and albuterol on muscle strength and volume in FSHD.\n Sixty-five patients were randomized to strength training of elbow flexors and ankle dorsiflexors or non-training. After 26 weeks albuterol (sustained-release, 8 mg BID) was added in a randomized, double-blind, placebo-controlled design. Primary outcome was maximum voluntary isometric strength (MVIC) at 52 weeks. Secondary outcomes comprised dynamic strength and muscle volume.\n Training and albuterol were well tolerated. Training of elbow flexors did not result in a significant effect on MVIC, but dynamic strength improved significantly. Elbow flexor MVIC strength increased significantly in albuterol vs placebo treated patients. Ankle dorsiflexor strength decreased in all groups. Eleven out of twelve non-trained muscles in the albuterol group showed a positive effect on MVIC compared to the placebo group (p < 0.05 in seven muscle groups). Muscle volume decreased in the placebo-treated, and increased in the albuterol-treated patients. No synergistic or antagonistic effects were observed between training and albuterol.\n In FSHD strength training and albuterol appear safe interventions with limited positive effect on muscle strength and volume. Consequences of prolonged use are presently unclear, which precludes routine prescription.", "What is the effect of wearing splints at night to stretch the plantarflexors on dorsiflexion range of motion (ROM) in people with Charcot-Marie-Tooth disease?\n Randomised, assessor-blinded, cross-over trial.\n 14 people (1 dropout) aged 7 to 30 years with Charcot-Marie-Tooth disease Type 1A and with < or = 15 degrees dorsiflexion range of motion (ROM).\n A splint holding the ankle in maximum dorsiflexion was worn nightly on one leg for 6 weeks followed by the opposite leg for the subsequent 6 weeks.\n The primary outcome was dorsiflexion ROM; secondary outcomes were eversion ROM, and dorsiflexion, eversion, and inversion strength, measured before and after splinting, and three months later.\n There was no significant difference between the experimental and the control intervention in terms of ROM or strength. Wearing the splint at night increased dorsiflexion ROM by 1 degree (95% CI -3 to 4; p = 0.72) and eversion ROM by 1 degree (95% CI -1 to 3; p = 0.28) compared to not wearing the splint. Wearing the splint increased dorsiflexion strength by 41 N (95% CI -53 to 135; p = 0.38), reduced eversion strength by 6 N (95% CI -112 to 101; p = 0.92) and reduced inversion strength by 8 N (95% CI -110 to 95; p = 0.88) compared to not wearing the splint.\n Wearing night splints does not increase ankle ROM or strength in people with Charcot-Marie-Tooth disease Type 1A.", "We performed a randomized controlled trial of early surgical treatment of contractures in 20 boys with Duchenne muscular dystrophy, age 4-6 yr. Surgery consisted of release of hip flexors, removal of iliotibial bands, and lengthening of tendo Achilles bilaterally. All patients were monitored for at least 12 months post-randomization, and assessed quantitatively for muscle strength and function. Surgery corrected the deformities, but had no beneficial effect on strength or function. Indeed, data in the second year showed more rapid deterioration of function in some of the operated boys. There appeared to be continued evolution of pathology following surgery, as assessed by sequential muscle ultrasound and muscle biopsy. We cannot recommend this type of surgery as a routine treatment.", "We recently reported a randomised controlled trial on the efficacy of strength training and the beta2-adrenergic agonist albuterol in patients with facioscapulohumeral muscular dystrophy (FSHD). Strength training and albuterol appeared safe interventions with limited positive effect on muscle strength and volume. We concurrently explored the prevalence and the characteristics of pain and fatigue in the participating FSHD patients, because these are probably underreported but clinically relevant symptoms in this disorder. Next, we studied the effects of albuterol and strength training on pain, experienced fatigue, health-related functional status and psychological distress.\n Sixty-five patients were randomised to strength training of elbow flexors and ankle dorsiflexors or non-training. After 26 weeks, albuterol (sustained-release, 8 mg bid) was added in a randomised, double-blind, placebo-controlled design. Outcomes comprised self-reported pain, experienced fatigue, functional status and psychological distress obtained with validated questionnaires at 52 weeks.\n Eighty percent of patients reported chronic persistent or periodic, multifocal pains. Thirty-four percent of the participants were severely fatigued. Strength training and albuterol failed to have a significant effect on all outcomes.\n Pain and fatigue are important features in FSHD. Strength training and albuterol do not have a positive or negative effect on pain, experienced fatigue, functional status and psychological distress." ]

[ "11704081", "17596638", "16035127", "18544724", "10440971", "12543279", "18070004", "9844752", "15600135", "12611749" ]

[ "The effects of light therapy on mini-mental state examination scores in demented patients.", "Light treatment for neuropsychiatric behaviors in Alzheimer's disease.", "Effect of timed bright light treatment for rest-activity disruption in institutionalized patients with Alzheimer's disease.", "Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial.", "A randomized, controlled trial of bright light therapy for agitated behaviors in dementia patients residing in long-term care.", "Dawn-dusk simulation light therapy of disturbed circadian rest-activity cycles in demented elderly.", "Melatonin and bright-light treatment for rest-activity disruption in institutionalized patients with Alzheimer's disease.", "Randomized, dim light controlled, crossover test of morning bright light therapy for rest-activity rhythm disorders in patients with vascular dementia and dementia of Alzheimer's type.", "Increased light exposure consolidates sleep and strengthens circadian rhythms in severe Alzheimer's disease patients.", "Effect of light on agitation in institutionalized patients with severe Alzheimer disease." ]

[ "Preliminary evidence suggests that demented patients may experience beneficial effects of light therapy. The authors tested whether bright light therapy (BLT) is capable of improving cognitive functions in patients with Alzheimer-type dementia (AD) or vascular dementia (VD).\n Twenty-three patients with AD or VD were randomly assigned to either evening BLT or dim light therapy (DLT). Effects of light therapy on cognitive functions were assessed before and after light therapy using Mini-Mental State Examination (MMSE) scores. Body temperature rhythm (BTR) was additionally recorded pre- and posttreatment.\n Irrespective of their diagnosis, patients treated with BLT (p =.0012) but not with DLT (p =.73) showed a statistically significant increase in MMSE total scores after light therapy. Evening BLT simultaneously induced a significant phase delay of 56 min on BTR (p =.025).\n Our preliminary results suggest that short-term evening BLT may exert beneficial effects on cognitive functioning in patients with dementia.", "Neuropsychiatric behaviors are common in people with Alzheimer's disease (AD) and make both professional and lay caregiving difficult. Light therapy has been somewhat successful in ameliorating disruptive behaviors. This randomized trial tested the effects of morning or afternoon bright light exposure compared with usual indoor light on the presence, frequency, severity, and occupational disruptiveness of neuropsychiatric behaviors in nursing home residents with AD. Light was administered for 1 hr daily (Monday-Friday) for 10 weeks. The Neuropsychiatric Inventory-Nursing Home was used to assess behavior at baseline and end of the intervention. Analyses revealed statistically significant differences between groups on agitation/aggression, depression/dysphoria, aberrant motor behavior, and appetite/eating disorders. The magnitude of change was small and may not represent clinically significant findings. Agitation/aggression and nighttime behaviors commonly occurred and were highly correlated with occupational disruptiveness. Interventions that decrease the presence and/or severity of neuropsychiatric behaviors have the potential to significantly decrease caregiver burden.", "Disturbances in rest-activity rhythm are prominent and disabling symptoms in Alzheimer's disease (AD). Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes. In most institutional environments, light levels are very low and may not be sufficient to entrain the circadian clock to the 24-hour day.\n The purpose of this randomized clinical trial was to test the effectiveness of timed bright light therapy in reducing rest-activity (circadian) disruption in institutionalized patients with AD. The experimental groups received either morning (9.30-10.30 am) or afternoon (3.30-4.30 pm) bright light exposure ( > or = 2500 lux in gaze direction) Monday through Friday for 10 weeks. The control group received usual indoor light (150-200 lux). Nighttime sleep, daytime wake, and rest-activity parameters were determined by actigraphy. Repeated measures analysis of variance was employed to test the primary study hypotheses.\n Seventy institutionalized subjects with AD (mean age 84) completed the study. No significant differences in actigraphy-based measures of nighttime sleep or daytime wake were found between groups. Subjects in either experimental light condition evidenced a significantly (p < 0.01) more stable rest-activity rhythm acrophase over the 10-week treatment period compared to the control subjects whose rhythm phase delayed by over two hours.\n One hour of bright light, administered to subjects with AD either in the morning or afternoon, did not improve nighttime sleep or daytime wake compared to a control group of similar subjects. However, exposure to one-hour of bright light in either the morning or afternoon may provide sufficient additional input to the circadian pacemaker to facilitate entrainment to the 24-hour day.\n (c) 2005 John Wiley & Sons, Ltd.", "Cognitive decline, mood, behavioral and sleep disturbances, and limitations of activities of daily living commonly burden elderly patients with dementia and their caregivers. Circadian rhythm disturbances have been associated with these symptoms.\n To determine whether the progression of cognitive and noncognitive symptoms may be ameliorated by individual or combined long-term application of the 2 major synchronizers of the circadian timing system: bright light and melatonin.\n A long-term, double-blind, placebo-controlled, 2 x 2 factorial randomized trial performed from 1999 to 2004 with 189 residents of 12 group care facilities in the Netherlands; mean (SD) age, 85.8 (5.5) years; 90% were female and 87% had dementia.\n Random assignment by facility to long-term daily treatment with whole-day bright (+/- 1000 lux) or dim (+/- 300 lux) light and by participant to evening melatonin (2.5 mg) or placebo for a mean (SD) of 15 (12) months (maximum period of 3.5 years).\n Standardized scales for cognitive and noncognitive symptoms, limitations of activities of daily living, and adverse effects assessed every 6 months.\n Light attenuated cognitive deterioration by a mean of 0.9 points (95% confidence interval [CI], 0.04-1.71) on the Mini-Mental State Examination or a relative 5%. Light also ameliorated depressive symptoms by 1.5 points (95% CI, 0.24-2.70) on the Cornell Scale for Depression in Dementia or a relative 19%, and attenuated the increase in functional limitations over time by 1.8 points per year (95% CI, 0.61-2.92) on the nurse-informant activities of daily living scale or a relative 53% difference. Melatonin shortened sleep onset latency by 8.2 minutes (95% CI, 1.08-15.38) or 19% and increased sleep duration by 27 minutes (95% CI, 9-46) or 6%. However, melatonin adversely affected scores on the Philadelphia Geriatric Centre Affect Rating Scale, both for positive affect (-0.5 points; 95% CI, -0.10 to -1.00) and negative affect (0.8 points; 95% CI, 0.20-1.44). Melatonin also increased withdrawn behavior by 1.02 points (95% CI, 0.18-1.86) on the Multi Observational Scale for Elderly Subjects scale, although this effect was not seen if given in combination with light. Combined treatment also attenuated aggressive behavior by 3.9 points (95% CI, 0.88-6.92) on the Cohen-Mansfield Agitation Index or 9%, increased sleep efficiency by 3.5% (95% CI, 0.8%-6.1%), and improved nocturnal restlessness by 1.00 minute per hour each year (95% CI, 0.26-1.78) or 9% (treatment x time effect).\n Light has a modest benefit in improving some cognitive and noncognitive symptoms of dementia. To counteract the adverse effect of melatonin on mood, it is recommended only in combination with light.\n controlled-trials.com/isrctn Identifier: ISRCTN93133646.", "Agitated behaviors are common in dementia patients residing in chronic care settings. Their occurrence may be associated with lack of adequate exposure to sunlight and with circadian rhythm disturbances.\n Prior research has suggested that bright light therapy (BLT) may reduce agitated behaviors in dementia patients. The aim of this study was to test the efficacy of BLT in a randomized, controlled, crossover clinical trial.\n Fifteen patients with dementia and agitated behaviors residing in a chronic care facility were randomized in a crossover design to morning BLT for 1 hour per day or to a control condition with dim light exposure. Patients were treated in either condition for 4 weeks, followed by 1 week on no treatment, prior to being crossed over to the other condition.\n Eight out of 15 patients completed the entire study. The rest completed at least 2 weeks of study. Patients randomized to the BLT condition exhibited a statistically significant improvement in nocturnal sleep from a mean of 6.4 hours/night to 8.1 hours/night 4 weeks later (p<0.05). The sleep of patients in the control condition did not improve significantly. There were no other significant differences between baseline and follow-up, nor between BLT and control treated patients on the other outcome measures, which included the Behavioral Pathology in Alzheimer Disease scale (Behave-AD) and the Cornell Scale for Depression in Dementia.\n Patients with dementia in chronic care who exhibit agitated behaviors sleep more hours at night when administered morning BLT. However, BLT does not lead to improvements in agitated behaviors in institutionalized patients with dementia with non-disturbed sleep-wake cycles.\n Copyright 1999 John Wiley & Sons, Ltd.", "We investigated whether low intensity dawn-dusk simulation (DDS), a 'naturalistic' form of light therapy designed to embed sleep in its accustomed phase, could improve the disturbed circadian rest-activity cycle, nocturnal sleep and and/or cognitive functions in dementia. A protocol of 3 weeks each of baseline, treatment and follow-up was completed by 13 patients (85yr old+/-5yr, MMSE 14+/-5; n=9 DDS versus n=4 'placebo' dim red light) who wore an activity/lux monitor throughout. There were no significant changes in clinical or cognitive status, nor modification of circadian stability or amplitude characteristics of the rest-activity cycle. However, two aspects of sleep responded to DDS but not to dim red light. The main sleep episode was 1:14h earlier during treatment (p=0.03) compared with before and after DDS. With respect to actimetry-determined sleep variables, the DDS group tended to have shortened 'sleep latency', longer 'sleep duration', more nocturnal immobility and less nocturnal activity than the dim red group (p<0.1). In parallel, nighttime light exposure tended to be reduced (p=0.07). These promising findings-after only 3 weeks of light treatment in elderly patients with advanced dementia-suggest that the circadian timing system remains functionally responsive even to low intensity DDS light. Increasing zeitgeber strength is an important strategy for improving sleep quality and timing in dementia, and DDS light therapy may provide one of the appropriate means to do so.", "To test whether the addition of melatonin to bright-light therapy enhances the efficacy in treating rest-activity (circadian) disruption in institutionalized patients with Alzheimer's disease (AD).\n Randomized, controlled trial.\n Two nursing homes in San Francisco, California.\n Fifty subjects (mean age 86) with AD.\n Experimental subjects received 1 hour of morning light exposure (> or = 2,500 lux in gaze direction) Monday to Friday for 10 weeks and 5 mg melatonin (LM, n=16) or placebo (LP, n=17) in the evening. Control subjects (n=17) received usual indoor light (150-200 lux).\n Nighttime sleep variables, day sleep time, day activity, day:night sleep ratio, and rest-activity parameters were determined using actigraphy.\n Linear mixed models were employed to test the primary study hypotheses. No significant differences in nighttime sleep variables were found between groups. At the end of the intervention, the LM group showed significant improvement in daytime somnolence as indicated by a reduction in the duration of daytime sleep, an increase in daytime activity, and an improvement in day:night sleep ratio. The LM group also evidenced a significant increase in rest-activity rhythm amplitude and goodness of fit to the cosinor model.\n Light treatment alone did not improve nighttime sleep, daytime wake, or rest-activity rhythm. Light treatment plus melatonin increased daytime wake time and activity levels and strengthened the rest-activity rhythm. Future studies should resolve the question of whether these improvements can be attributed to melatonin or whether the two zeitgebers interact to amplify efficacy.", "The authors compared the therapeutic effect of morning bright and dim light exposure on rest-activity (R-A) rhythm disorders in patients with vascular dementia (VD) and patients with dementia of Alzheimer's type (DAT). Participants in this study were 12 patients with VD (M/F = 5/7; average age = 81 years) and 10 patients with DAT (M/F = 4/6; average age = 78 years). They were exposed to 2 weeks of bright light (BL; 5000-8000 lux) and 2 weeks of dim light (DL; 300 lux) in the morning (09:00-11:00) in a randomized crossover design in which the 2-week treatment period took place between pretreatment (1 week) and posttreatment (1 week) periods. Continuous R-A monitoring was performed at 1-minute intervals throughout the study using an actigraph around the nondominant wrist. The BL exposure for 2 weeks induced a significant reduction in both nighttime activity and percentages of nighttime activity to total activity compared with the pretreatment period, as well as compared with the DL condition in the VD group, but not in the DAT group. These findings support the assumption that the therapeutic efficacies of morning BL exposure are prominent in VD patients and are mainly due to its photic effect rather than nonphotic effects such as the intensification of social interaction accompanying light therapy.", "Sleep in the nursing home environment is extremely fragmented, possibly in part as a result of decreased light exposure. This study examined the effect of light on sleep and circadian activity rhythms in patients with probable or possible Alzheimer's disease. Results showed that both morning and evening bright light resulted in more consolidated sleep at night, as measured with wrist actigraphy. Evening light also increased the quality of the circadian activity rhythm, as measured by a 5-parameter extended cosine model (amplitude, acrophase, nadir, slope of the curve, and relative width of the peak and trough). Increasing light exposure throughout the day and evening is likely to have the most beneficial effect on sleep and on circadian rhythms in patients with dementia. It would behoove nursing homes to consider increasing ambient light in multipurpose rooms where patients often spend much of their days.", "Preliminary data suggest that morning bright light might improve symptoms of agitation, a serious problem in patients with dementia. The authors expand on an earlier pilot study by evaluating the effect of bright light therapy on agitated behavior in a large sample of patients with severe dementia.\n Ninety-two patients were randomly assigned to morning bright light, morning dim red light, or evening bright light. Agitation was rated by research staff who observed the patients every 15 minutes throughout the treatment period and by caregivers at one time-point before and one time-point after treatment.\n Morning bright light delayed the acrophase of the agitation rhythm by over 1.5 hours. Bright light was associated with improved caregivers' ratings but had little effect on observational ratings of agitation.\n Although the result that light shifted the peak of the agitated behavior might be generalizable to patients with milder forms of AD, the fact that agitation was not ameliorated might not be. Because the suprachiasmatic nucleus (SCN) of patients with severe AD is likely to be more degenerated, and the circadian activity rhythms deteriorate as the disease progresses, it is still possible that patients with more intact SCNs, that is, patients with mild or moderate AD, might benefit from light treatment even more than those with severe AD." ]

[ "2891940", "16967580", "9855523", "12351281", "11009230", "1712433", "8196572", "9833745", "10680784", "1594260", "14745057", "3103044", "15025615", "12859309", "8857633", "11964590", "8610220", "8997461", "8803379", "10638902", "8630199", "10588558", "10388248", "1312797", "9314641", "3822496" ]

[ "Mexiletine for treatment of chronic painful diabetic neuropathy.", "A randomized double-blind crossover trial of intravenous lidocaine in the treatment of neuropathic cancer pain.", "A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team.", "The analgesic effect of gabapentin and mexiletine after breast surgery for cancer.", "Efficacy of oral mexiletine for neuropathic pain with allodynia: a double-blind, placebo-controlled, crossover study.", "Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia.", "[Mexiletine in treatment of painful diabetic neuropathy].", "Mexiletine for HIV-infected patients with painful peripheral neuropathy: a double-blind, placebo-controlled, crossover treatment trial.", "Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study.", "Lidocaine test in neuralgia.", "Systemic lidocaine in pain due to peripheral nerve injury and predictors of response.", "The analgesic effect of tocainide in trigeminal neuralgia.", "The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injury.", "The effectiveness of intravenous ketamine and lidocaine on peripheral neuropathic pain.", "Computer-controlled lidocaine infusion for the evaluation of neuropathic pain after peripheral nerve injury.", "Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized double-blind, active placebo-controlled, crossover trial.", "Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine.", "Mexiletine in the symptomatic treatment of diabetic peripheral neuropathy.", "Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study.", "Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II.", "Effect of mexiletine on spinal cord injury dysesthetic pain.", "Intravenous lidocaine, amantadine, and placebo in the treatment of sciatica: a double-blind, randomized, controlled study.", "A trial of intravenous lidocaine on the pain and allodynia of postherpetic neuralgia.", "The use of oral mexiletine for the treatment of pain after peripheral nerve injury.", "Efficacy and safety of mexiletine in the treatment of painful diabetic neuropathy. The Mexiletine Study Group.", "Intravenous lidocaine infusion--a new treatment of chronic painful diabetic neuropathy?" ]

[ "Sixteen of nineteen patients completed a randomised double-blind crossover trial to assess the effect of oral mexiletine (10 mg/kg bodyweight daily) on the symptoms and signs of chronic painful diabetic neuropathy. The median age of the sixteen patients was 50 years (range 30-64). Assessment with a five-item clinical symptom scale showed significant improvement during the mexiletine phase compared with the placebo phase. Pain was reduced during mexiletine but not during placebo, as assessed by a visual analogue rating scale. Mexiletine treatment had no effect on tendon reflexes, vibration threshold levels, beat-to-beat variation in heart rate during deep breathing, and postural blood pressure response. Mild side-effects were seen in three of the sixteen patients during mexiletine treatment.", "In a randomized, double-blind, crossover study, we evaluated the effect of intravenous lidocaine (5 mg/kg body weight over 30 min) on the neuropathic pain of advanced cancer patients. Pain intensity, assessed by a visual analogue scale, did not show any significant difference between lidocaine and placebo infusion. The blinded choice of patients and investigators also suggested no significant improvement from lidocaine when given by this regimen. Intravenous lidocaine does not appear to have a significant analgesic effect on neuropathic cancer pain.", "Painful sensory neuropathy is a common complication of HIV infection. Based on prior uncontrolled observations, we hypothesized that amitriptyline or mexiletine would improve the pain symptoms.\n A randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or matching placebo. The primary outcome measure was the change in pain intensity between baseline and the final visit.\n The improvement in amitriptyline group (0.31+/-0.31 units [mean+/-SD]) and mexiletine group (0.23+/-0.41) was not significantly different from placebo (0.20+/-0.30). Both interventions were generally well tolerated.\n Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy.", "We investigated the analgesic efficacy of mexiletine and gabapentin on acute and chronic pain associated with cancer breast surgery in 75 patients. They were randomized to receive, in a double-blinded manner, mexiletine 600 mg/d, gabapentin 1200 mg/d, or placebo for 10 days. Anesthesia was standardized, and all patients had access to routine postoperative analgesics on demand. The visual analog scale score assessed pain at rest and after movement. Three months later, all patients were interviewed to identify intensity of chronic pain and analgesic requirements. Mexiletine and gabapentin reduced codeine consumed from the second to tenth day by 50% (P = 0.029; P = 0.018 and P = 0.035 for mexiletine versus control and gabapentin versus control comparisons, respectively). Total paracetamol consumption was also reduced during the same time (P = 0.0085; P = 0.007 and P = 0.011 for the mexiletine and gabapentin groups when compared with the control, respectively). Pain at rest and after movement was reduced by both drugs on the third postoperative day. Pain after movement also was reduced by gabapentin between the second and fifth postoperative day. Three months later, the incidence of chronic pain, its intensity, and need for analgesics were not affected by either treatment. However, burning pain was more frequent in the control group (P = 0.033).\n Patients undergoing breast surgery for cancer may develop chronic pain. We evaluated the effect of mexiletine and gabapentin on the acute and chronic pain after breast surgery for cancer. Both drugs reduced the postoperative analgesic requirements, and particularly, gabapentin reduced pain after movement. The overall incidence of chronic pain was unaffected except for burning pain.", "Mexiletine is an oral sodium channel antagonist that has been reported to be effective in a variety of neuropathic pain syndromes. However, recent reports question the efficacy of oral mexiletine in neuropathic pain. The objectives of this study were to examine the effect of oral mexiletine on pain, neurosensation, allodynia, and quality of life.\n Twenty subjects suffering from neuropathic pain with prominent allodynia were enrolled in a randomized placebo-controlled crossover study. Patients were titrated to a maximum dose of 900 mg/d or dose-limiting side effects, whichever occurred first. At baseline and on days 0, 4, 7, and 10, the following tests were performed: (1) Quality of Life Questionnaires; (2) pain scores; (3) area of allodynia; (4) side effects; (5) neurosensory testing; and (6) peak and trough plasma mexiletine levels.\n Peak plasma levels occurred on day 10 and were 0.54 microg/mL. There was no significant effect on any quality of life measurement. There was no significant effect on any neurosensory threshold or the area of allodynia. There was a significant effect of mexiletine on stroking-induced pain. There were no significant effects on any other pain score. Side effects were negligible.\n At doses of up to 900 mg/d, mexiletine has minimal effects on pain and allodynia of neuropathic pain. However, side effects may preclude higher doses.", "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.", "The objective of this double-blind placebo controlled multicenter study was to prove the efficacy of mexiletine in painful diabetic neuropathy. Treatment was provided for in three dosages. For pain measurements a visual analogue scale (VAS) and McGill's verbal rating scale were chosen. 95 patients were included. A global assessment of the VAS showed no differences in treatment. The total evaluation (PRIT = Pain Rating Index Total) of the McGill scale just failed the level of significance. More specific exploratory evaluation of subclasses of the McGill scale, representing different qualities of pain, gave remarkable differences between mexiletine and placebo. According to types of complaints an evaluation showed substantial advantages of the mexiletine treatment with both the VAS and the McGill scale. There is strong evidence that particularly patients with stabbing or burning pain, heat sensations or formication will benefit most by mexiletine therapy. Concerning the dosage, a medium regimen of 450 mg per day seems to be appropriate in this indication. With an increase in dosage the efficacy does not rise proportionally. Mexiletine proved a very safe therapy with negligible side effects at the medium dose range, even less than placebo. There were no cardiovascular side effects. Further investigations should pay more attention to the variety of the complaints and include the quality of life.", "Although mexiletine, an antiarrhythmic with local anesthetic properties, has been reported to relieve discomfort in diabetic neuropathy, its usefulness in the treatment of HIV-related painful peripheral neuropathy (PPN) has not been determined. The tolerance and effectiveness of mexiletine in HIV-related PPN were assessed in 22 patients who were randomized to receive mexiletine (maximum dose, 600 mg/day) or placebo for 6 weeks, followed by the alternative intervention for 6 weeks after a 1-week washout period. The daily pain response was assessed using a visual analogue scale card in 19 patients who received at least 2 weeks of the drug, 16 of whom were crossed-over to receive the alternate agent. No statistically significant difference was found between the mean daily pain scores for patients receiving mexiletine versus placebo, irrespective of the order in which the agents were received. Comparing the mean individual daily pain scores for each phase of study, 5 patients (31%) had significantly less pain while receiving mexiletine compared with their response to placebo, 5 patients (31%) had significantly less pain while receiving placebo, and no difference was noted in 6 patients (38%). Crossover and multivariate analyses for repeated measures showed no apparent difference in the response to mexiletine versus placebo. Dose-limiting adverse events occurred in 39% of those receiving mexiletine, but only 1 patient (5%) discontinued placebo. Mexiletine was only modestly well tolerated despite its relatively brief period of administration, and no evidence was found to support its benefit in HIV-related PPN. Although a first-drug effect was not demonstrated, a powerful placebo effect was seen in some patients.", "To investigate the effects of systemic administration of lidocaine on different components of neuropathic central pains by quantitative sensory testing.\n The efficacy of systemic lidocaine (5 mg/kg IV over 30 minutes) was evaluated in a double-blind, placebo-controlled, and cross-over fashion, on both spontaneous ongoing pain and evoked pains (allodynia and hyperalgesia) in 16 patients with chronic poststroke (n = 6) or spinal cord injury (n = 10) related pain.\n Lidocaine was significantly superior to the placebo (saline) in reducing the intensity of spontaneous ongoing pain for up to 45 minutes after the injection: 10 of 16 patients (62.5%) receiving lidocaine showed a significant reduction in spontaneous pain, whereas only six patients showed this after the placebo. Lidocaine also significantly reduced the intensity of brush-induced allodynia and mechanical hyperalgesia, but was no better than the placebo against thermal allodynia and hyperalgesia. In general, the side effects were moderate and consisted mainly of lightheadedness (44%).\n Systemic lidocaine can induce a significant and selective reduction of several components of pain caused by CNS injuries. The observed preferential antihyperalgesic and antiallodynic effects of this drug suggest a selective central action on the mechanisms underlying these evoked pains.", "Ten patients with organic nerve injury causing chronic neuropathic pain were tested for the effects of intravenous lidocaine versus saline upon psychophysical somatosensory variables. The variables assessed were the subjective magnitude of pain, area of mechanical hyperalgesia and presence and magnitude of thermal heat/cold hyperalgesia. The study methods applied to evaluate these conditions were the conventional testing of somatosensory submodalities with area mapping and the subjective magnitude estimation of spontaneous pain. It was found that spontaneous pain and mechanical hyperalgesia were consistently improved, transiently, by intravenous administration of lidocaine in all 10 patients; areas of hyperalgesia which extended beyond the territory of the nerve also improved transiently. Spontaneous pain and mechanical hyperalgesia, but not hypoesthesia, were transiently improved by injection of saline in only 1 of the 10 patients. This outcome is probably due to a placebo effect. This improvement is in keeping with the inhibition of anomalous neural impulses which can be generated anywhere along the sensory channels responsible for generating spontaneous pain and hyperalgesia. Thus, intravenous lidocaine is proposed as a diagnostic aid in the examination of patients complaining of complex sensory disorders associated with nerve injury. The transient pain relief may allow a fuller identification of the area of sensory loss.", "To investigate the effects of IV lidocaine on spontaneous and evoked pain (allodynia and hyperalgesia) due to peripheral nerve injury (postherpetic neuralgia or nerve trauma) using quantitative sensory testing.\n The authors randomized 22 patients to receive lidocaine 5 mg/kg IV during 30 minutes or placebo in a double-blind crossover design and 16 patients subsequently received mexiletine on an open basis titrated from 400 to 1,000 mg per day (mean 737 mg/day).\n Lidocaine induced a significant decrease in ongoing pain for up to 6 hours with a peak effect 60 to 120 minutes postinjection. The drug also decreased mechanical dynamic allodynia and static (punctate) mechanical allodynia/hyperalgesia, but not thermal allodynia and hyperalgesia. The effects of lidocaine and mexiletine on spontaneous pain intensity were significantly higher in patients with concomitant mechanical allodynia in comparison with those without allodynia.\n These data indicate modality-specific antihyperalgesic effects of IV lidocaine in patients with peripheral nerve injury. Patients with mechanical allodynia may be good candidates for treatment with local anesthetic-like drugs and possibly with other sodium-channel blockers.", "Tocainide is a derivative of lidocaine with anti-arrhythmic action and, unlike lidocaine, can be used for oral treatment. Tocainide was alternatively with carbamazepine given to 12 patients with trigeminal neuralgia in a double-blind cross-over study for 2 weeks. The analgesic effect was estimated each day by the patients using a 0-10-point scale summarizing the frequency and severity of the attacks. The similarity in analgesic effect of the two drugs was striking. A possible analgesic mechanism could be that tocainide blocks the sodium channels in the hyperexcitable nerve membranes in the pain-producing foci in trigeminal neuralgia.", "Pain following spinal cord injury (SCI) is a therapeutic challenge. Only a few treatments have been assessed in randomized, controlled trials. The primary objective of the present study was to examine the analgesic effect of ketamine and lidocaine in a group of patients with neuropathic pain below the level of spinal cord injury. We also wanted to assess sensory abnormalities to see if this could help us to identify responders and if treatments resulted in changes of sensibility.\n Ten patients with spinal cord injury and neuropathic pain below the level of injury were included. The analgesic effect of ketamine 0.4 mg kg(-1) and lidocaine 2.5 mg kg(-1) was investigated. Saline was used as placebo. The drugs were infused over 40 min. A randomized, double-blind, three-period, three-treatment, cross-over design was used. Systemic plasma concentrations of ketamine and lidocaine were assessed. Pain rating was performed using a visual analogue scale (VAS). Sensory function was assessed with a combination of traditional sensory tests and quantitative measurement of temperature thresholds.\n Response to treatment, defined as 50% reduction in VAS-score during infusion, was recorded in 5/10 in the ketamine, 1/10 in the lidocaine and 0/10 in the placebo groups. Neither ketamine nor lidocaine changed temperature thresholds or assessments of mechanical; dynamic and static sensibility. Nor could these sensory assessments predict response to treatment in this setting. Lidocaine and particularly ketamine were associated with frequent side-effects.\n Ketamine but not lidocaine showed a significant analgesic effect in patients with neuropathic pain after spinal cord injury. The pain relief was not associated with altered temperature thresholds or other changes of sensory function.", "Neuropathic pain is often severe and resistant to pharmacological treatment. The aims of the present study were to assess the analgesic effect of ketamine and lidocaine and to investigate if measurement of different variables of sensibility could be used to identify responders. We also wanted to study if treatment resulted in changes of sensibility.\n Twelve patients with long-lasting peripheral neuropathic pain of traumatic origin were included. The effects of ketamine hydrochloride (Ketalar, Parke Davis) 0.4 mg/kg and lidocaine hydrochloride (Xylocain, Astra) 2.5 mg/kg were investigated. Saline was used as placebo. The intensity of continuous pain was measured by a visual analogue scale (VAS). Warm and cold perception as well as heat and cold pain thresholds were assessed. Sensibility to touch was also tested. Systemic plasma concentrations of lidocaine and ketamine were assessed.\n The mean reduction in VAS-scores was 55%, 34% and 22% for ketamine, lidocaine and placebo, respectively. A significant difference was registered between ketamine and placebo (P = 0.009). Response to treatment (50% reduction in VAS-score during infusion) was recorded in 7/12 in the ketamine, 4/12 in the lidocaine and 2/12 in the placebo group. Quantitative sensory testing (QST) of thermal sensitivity and sensory tests for mechanical stimuli could not separate responders from non-responders and neither were the results from these assessments changed by the infusion of the drugs. Lidocaine and particularly ketamine were associated with frequent side-effects, the most common being somnolence and dizziness.\n Ketamine showed a significant analgesic effect. The clinical usefulness is, however, limited by disturbing side-effects.", "Systemic lidocaine has been reported to be effective in treating several neuropathic pain syndromes. Few reports relate plasma lidocaine concentration to analgesia and the available studies have been complicated by labile plasma lidocaine concentrations. We used a computer-controlled infusion pump (CCIP) to target and maintain stable plasma lidocaine concentrations and study the effect of intravenous lidocaine on (1) pain scores, (2) current perception thresholds, (3) side effects, and (4) pain distribution in patients suffering from peripheral nerve injury pain.\n This study used a randomized double-blind placebo-controlled design. Eleven patients suffering from neuropathic pain after peripheral nerve injury received both a lidocaine and saline infusion in separate study sessions. The order of the study sessions was randomized and separated from each other by 1 week. The CCIP was programmed to target plasma lidocaine concentrations of 0.5, 1, 1.5, 2, and 2.5 micrograms/ml, each held for 10 min. Pain scores and pain distribution were assessed in the painful area, and electrical current perception thresholds (CPT) of the ring finger were measured using a cutaneous perception threshold neurometer (Neurometer CPT, Neurotron, Baltimore, MD). Side effects were recorded at fixed intervals. Plasma lidocaine concentrations were measured at 4 and 9 min after each step increase in infusion and correlated with the observed effects.\n Saline infusion had no effect. However, with lidocaine there was a significant plasma concentration-dependent decrease in pain scores starting at 1.5 micrograms/ml. This effect typically corresponded with a decrease in the size of the receptive field to which the pain was referred. For the electrical stimulus, there was no significant effect on cutaneous perception at 2000-Hz stimulation at the highest concentration examined; however, there was a significant increase in thresholds at 250-Hz (starting at 1.5 micrograms/ml) and 5-Hz (starting at 1.0 micrograms/ml) stimulation. There were no serious side effects. In all, 54.5% of patients reported lightheadedness (average plasma lidocaine concentration: 1.5 micrograms/ml) and one patient reported nausea (2.3 micrograms/ml).\n The computer-controlled delivery of intravenous lidocaine results in relatively stable plasma concentrations which allows a more thorough evaluation of the relationship between plasma concentration and patient response. This administration methodology for intravenous lidocaine may prove to be a valuable clinical and research tool.", "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.", "Pain intensity, muscle strength, static muscle endurance, pressure pain threshold, and pain tolerance at tender points and control points were assessed in 31 patients with fibromyalgia (FM), before and after intravenous administration of morphine (9 patients), lidocaine (11 patients), and ketamine (11 patients). The three different studies were double-blind and placebo-controlled. The patients were classified as placebo-responders, responders (decrease in pain intensity by > 50%) and non-responders. The morphine test did not show any significant changes. The lidocaine test showed a pain decrease during and after the infusion. The ketamine test showed a significant reduction in pain intensity during and after the test period. Tenderness at tender points decreased and endurance increased significantly, while muscle strength remained unchanged. The present results support the hypothesis that the NMDA receptors are involved in pain mechanisms in fibromyalgia. These findings also suggest that central sensitization is present in FM and that tender points represent secondary hyperalgesia.", "To evaluate the efficacy and safety of mexiletine in the symptomatic treatment of diabetic peripheral neuropathy (DPN).\n In this prospective, double-blind study, 29 patients were randomized to receive mexiletine 600 mg/d or matching placebo for 3 weeks. A four-item symptom score (FIS), which rated pain, dysesthesias, paresthesias, and nightly exacerbations of symptoms, and a 100-mm visual analog scale (VAS), which rated pain intensity, were completed by patients before and after treatment. At the end of treatment independent patient and investigator global assessments were made. Patients reported adverse effects after 1 and 3 weeks of treatment.\n Treatment groups were similar at baseline. The difference between the median changes in FIS scores (mexiletine = 5.5, placebo = 2) was not statistically significant. Overall symptom response was similar in both treatment groups as demonstrated by both global assessments (p = 0.19). The mean change in VAS score from baseline to posttreatment was determined for both groups and the difference between these mean scores was 16.5 mm (95% CI, -7.1 to 40.2 mm) (p = 0.16). Inadequate statistical power (1-beta = 0.40) may have resulted from small sample size, small magnitude of effect, or variability in the measured effect. Adverse effects were more common in the mexiletine group, though not statistically significant. One patient receiving mexiletine was hospitalized for palpitations.\n Because of conflicting reports of mexiletine's efficacy in the treatment of symptomatic DPN, this drug should be reserved for patients unresponsive or intolerant to standard therapy, without evidence of heart disease, and with sensations of burning heat, formication, or stabbing pain.", "The local anesthetic sodium-channel blockers lidocaine and mexiletine reduce spontaneous and evoked activity in experimental neuroma models and have been reported to relieve a variety of clinical neuropathic pain conditions. The predictive value of relief from an intravenous lidocaine infusion (IVL) for subsequent relief from a 4-week trial of oral mexiletine was assessed in a prospective study of nine subjects with chronic neuropathic pain of peripheral origin. Subjects received IVL, 2 mg/kg and 5 mg/kg, over 45 min during separate sessions in random order under double-blind conditions. One week later, a 4-week titrating trial of oral mexiletine was initiated. Both doses of IVL significantly reduced pain visual analogue scores (VAS) scores. Although IVL 5 mg/kg produced significantly higher pain relief scores than IVL 2 mg/kg, subjects responded in a highly consistent manner to the two IVL. Subsequent response to oral mexiletine was significantly correlated with the average response to the two IVL. Mexiletine dose and blood levels were not correlated with pain relief. The results suggest that IVL may be a valuable tool in selecting patients for oral therapy with analogous drugs.", "Several lines of evidence suggest that neuropathic pain (including Complex Regional Pain Syndrome [CRPS] I and CRPS II) is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons. This study sought to characterize the effects of intravenous lidocaine (a sodium channel blocker) on acute sensory thresholds within the painful area and the size of the painful area in patients suffering from CRPS I and II.\n This study used a randomized, double-blind, placebo-controlled design in 16 subjects suffering from CRPS I and II with a prominent allodynia. Each subject received an intravenous infusion of lidocaine and diphenhydramine separated by 1 week. A computer-controlled infusion pump targeted stair-step increases in plasma levels of lidocaine of 1, 2, and 3 microg/ml. At baseline and at each plasma level, spontaneous and evoked pain scores and neurosensory testing within the painful area were measured. The neurosensory testing consisted of thermal thresholds, tactile thresholds and the area of allodynia to punctate, and stroking and thermal stimuli.\n Intravenous lidocaine and diphenhydramine had no significant effect on the cool, warm, or cold pain thresholds. However, lidocaine caused a significant elevation of the hot pain thresholds in the painful area. Intravenous lidocaine caused a significantly decreased response to stroking and cool stimuli in the allodynic area. There was also a significant decrease in pain scores to cool stimuli at all plasma levels and the spontaneous pain at the highest plasma level.\n This study demonstrates that intravenous lidocaine affects pain in response to cool stimuli more than mechanical pain in subjects with neuropathic pain. There is a lesser effect on spontaneous pain and pain induced by stroking stimuli and no effect on the pain induced by punctate stimuli.", "Severe pain occurs in 5-30% of the spinal cord-injured (SCI) population and is difficult to treat. Subarachnoid lidocaine has been used in selected patients with some success. Mexiletine, an analog of lidocaine that acts at Na+/K+ channels in the peripheral nerve, has been found effective in persons with diabetic dysesthetic neuropathy. The effect of mexiletine in the treatment of spinal cord dysesthetic pain was examined in this study. Fifteen patients were enrolled, and 11 patients completed the prospective, randomized, placebo-controlled, double-blind, crossover design trial. Inclusion/exclusion criteria were carefully defined. A 1-wk washout period was followed by a 4-wk drug trial of either mexiletine (450 mg/day) or placebo. This was repeated for the second medication in the second arm of the study. Patients were followed weekly with McGill and visual analog pain scales. Baseline, midpoint, and endpoint Barthel function scores were recorded. The Wilcoxon's signed-rank test and paired t test were used for statistical analysis. Results showed no significant effect of mexiletine on SCI dysesthetic pain scales or Barthel index. In conclusion, in this trial, mexiletine did not appear to decrease spinal cord injury-related dysesthetic pain.", "Sciatica is a neuropathic pain syndrome caused by compression and/or inflammation of spinal nerve roots by herniated disc material, and its treatment is therefore usually aimed at reducing compression and inflammation. Studies have shown that both systemic local anesthetics and N-methyl-D-aspartate (NMDA) receptor antagonists may produce analgesia in a variety of neuropathic pain syndromes. The present study evaluated the analgesic efficacy of i.v. infusions of the local anesthetic lidocaine, the NMDA receptor antagonist amantadine, and a placebo in sciatica.\n Thirty patients with sciatica, as confirmed by physical examination and imaging studies, were enrolled in a randomized, double-blind, three-arm crossover trial. Infusions of amantadine (2.5 mg/kg), lidocaine (5 mg/kg), and a placebo were administered over a 2-hour period, 2-7 days apart from each other. Spontaneous pain (visual analog scale) and evoked pain (straight leg raise) were measured every 30 minutes for 3 hours.\n Lidocaine reduced spontaneous pain as compared with amantadine and with the placebo for all measurements and at a significant level at the 30 (P < .05), 120, and 180 (P < .01) minute time points. Maximal pain reduction from the baseline was 62 +/- 7% for lidocaine, 43 +/- 7% for amantadine, and 47 +/- 7% for the placebo. Straight leg raise test also significantly improved with lidocaine (from 30 to 37 degrees; P < .05), as compared to amantadine (34-36 degrees) and to the placebo (32-34 degrees). All three treatments were relatively well tolerated.\n Intravenous lidocaine, rather than amantadine, reduces both spontaneous and evoked sciatic pain.", "This study investigated the effect of intravenous lidocaine at two doses (1 mg/kg and 5 mg/kg over 2 hours) and an intravenous saline placebo on the pain and allodynia of postherpetic neuralgia (PHN). Twenty-four patients were studied using a randomized, double-blind, within-patient crossover design. Each patient received normal saline, lidocaine 0.5 mg/kg/h, and lidocaine 2.5 mg/kg/h for a 2-h period. The McGill Pain Questionnaire Short Form, visual analogue scores (VAS), and area of allodynia were measured at intervals during the infusions. Free plasma lidocaine levels were also measured. The results were statistically analyzed using Student's t-test for paired data. The VAS for ongoing pain showed a significant reduction after all the infusions (P < 0.05). For dynamic pressure-provoked pain, the VAS was unaffected by placebo but showed a reduction at an equal level of significance with both lidocaine infusions (P < 0.05). The area of allodynia of PHN, as mapped by brush stroke, declined in association with intravenous lidocaine (0.5 mg/kg/h = P < 0.05; 2.5 mg/kg/h = P < 0.001). Placebo had no significant effect on the area of allodynia. These findings demonstrate a positive effect on pain and allodynia following a brief intravenous infusion of lidocaine. The higher dose infusion may produce plasma levels in the toxic range, with no significant clinical increase in response.", "Neuropathic pain is often a difficult condition to treat. Clinical and laboratory studies using intravenously administered local anesthetics or antiarrhythmic agents support the use of these drugs for the treatment of neuropathic pain. The availability of the oral antiarrhythmic medication, mexiletine, has made it possible to study the effects of an orally administered medication on chronic neuropathic pain. The study used a double-blind placebo-controlled design to examine 11 subjects in whom treatment with conventional pain medications had been unsuccessful. Subjects had a history of peripheral nerve injury or dysfunction, and all complained of symptoms consistent with neuropathic pain. After baseline pain measurements, mexiletine or placebo was given in gradually increasing doses to a maximum daily dose of 750 mg mexiletine. After 1 month at steady state, the subject received the alternative medication. Mexiletine was found to produce a statistically significant reduction in reported pain when compared to baseline or placebo. Pain scores were rated on a scale from 0 (no pain) to 10 (unbearable pain). Median pain scores prior to mexiletine were 7, after placebo treatment 7, and while receiving mexiletine (750 mg/day) 4. Side effects were mild and well-tolerated. Mexiletine may be effective in reducing neuropathic pain for patients in whom alternative pain medications have been unsatisfactory.", "To investigate the efficacy and safety of mexiletine in the treatment of painful diabetic neuropathy.\n A total of 216 insulin-treated diabetes patients with painful diabetic neuropathy were randomly allocated to three dosages of mexiletine or placebo. The Visual Analog Scale (VAS) for pain/discomfort was scored each day during daytime and nighttime, and sleeping disturbances were also recorded by the patients. Plasma levels of mexiletine and 24-h electrocardiogram (ECG) mapping were assessed before and during the 3-week study period.\n A significant reduction in sleep disturbances and pain during nighttime was observed in the group of patients taking the highest dosages (675 mg/day) of mexiletine compared with the other groups. No significant correlation was found between plasma concentration of mexiletine and the therapeutic effect or adverse events. No serious adverse events were seen. The 24-h ECG mapping did not disclose onset of significant arrhythmias in any patient.\n Mexiletine in a dosage of 675 mg daily can reduce pain caused by diabetic neuropathy, and the effect of this drug appears to have a rapid onset.", "In a randomized double-blind, cross-over study the effect of intravenous lidocaine (5 mg/kg body weight) on the symptoms and signs of painful diabetic neuropathy of more than 6 months duration has been evaluated. Using a clinical symptom scale, there was significant beneficial effect 1 and 8 days after lidocaine infusion compared to after saline infusion (P less than 0.05 and P less than 0.02, respectively). The duration of the individual effect ranged from 3 to 21 days. Lidocaine infusion had no effect on the objective measurements of neuropathy. Intravenous lidocaine infusion seems to be a new alternative treatment of chronic painful diabetic neuropathy." ]

[ "16750808", "22926182", "17356445", "12774876" ]

[ "Randomized controlled trial evaluating the effects of cobedding on weight gain and physiologic regulation in preterm twins in the NICU.", "Cobedding and recovery time after heel lance in preterm twins: results of a randomized trial.", "Co-bedding twins: how pilot study findings guided improvements in planning a larger multicenter trial.", "Co-bedding versus single-bedding premature multiple-gestation infants in incubators." ]

[ "To compare the differences in growth and physiologic regulation in cobedded preterm twins versus individually bedded preterm twins while in the neonatal intensive care unit (NICU).\n Infants born between 28 to 34 weeks gestation in a Level III NICU were eligible for enrollment into the study. Forty-nine sets of twins were enrolled in the study and 41 sets were ultimately analyzed. There were 21 twin sets (42 infants) in the experimental group and 20 sets (40 infants) in the control group.\n A prospective randomized design was used.\n Parents of twins in a level III NICU were approached for consent to participate in the study. Twins were randomized using sealed envelopes that designated placement in either the control or experimental group. Twin sets who were randomized to the control group received routine care in separate beds. Twin sets in the experimental group received routine care in the same bed. Guidelines for positioning of cobedded twins were utilized. Treatment and data collection started when infants met the inclusion criteria for the study.\n Measurements of weekly weight gain and episodes of apnea/bradycardia/desaturation (A/B/D) were collected for each group.\n After adjusting for baseline weight in an analysis of covariance model, the cobedded group demonstrated a significantly higher mean weight compared to the control group at week 1 (1,644 vs. 1,572 grams, respectively, F = 11.6, P = 0.001) and at week 2 (1,755 vs. 1,693 grams, respectively, F = 5.7, P = 0.02). There was no difference in the median number of total combined A/B/D episodes between the 2 groups.\n A greater increase in mean weight gain was noted in the cobedded group compared to the control group.", "Cobedding of preterm twin infants provides tactile, olfactory, and auditory stimulation and may affect pain reactivity. We carried out a randomized trial to assess the effect of cobedding on pain reactivity and recovery in preterm twin neonates.\n Stable preterm twins (n = 67 sets) between 28 and 36 weeks of gestational age were randomly assigned to a cobedding group (cared for in the same incubator or crib) or a standard care group (cared for in separate incubators or cribs). Pain response (determined by the Premature Infant Pain Profile [PIPP]) and time to return to physiologic baseline parameters were compared between groups with adjustment for the nonindependence of twin infants.\n Maternal and infant characteristics were not significantly different between twin infants in the cobedding and standard care groups except for 5-minute Apgar <7 and postnatal age and corrected gestational age on the day of the heel lance. Mean PIPP scores were not different between groups at 30, 60, or 120 seconds. At 90 seconds, mean PIPP scores were higher in the cobedding group (6.0 vs 5.0, P = .04). Recovery time was shorter in the cobedding group compared with the standard care group, (mean = 75.6 seconds versus 142.1 seconds, P = .001). No significant adverse events were associated with cobedding. Adjustment for nonindependence between twins and differences in baseline characteristics did not change the results.\n Cobedding enhanced the physiologic recovery of preterm twins undergoing heel lance, but did not lead to lower pain scores.", "Co-bedding, a developmental care practice for twins and multiples, has been theorized as a strategy to decrease the adverse neurodevelopmental effects that may be associated with hospitalization.\n The aim of this study was to determine the feasibility of study design, methods, and the measurement of desired outcomes for the development of a larger multicentered study.\n Study findings were used to estimate effect size, determine staff and bedside care organization, evaluate feasibility of data collection measures, and identify issues related to recruitment and follow-up. Results were incorporated in the development of a larger multicentered trial grant proposal.\n Pilot studies can play an important role in the development of a competitive grant proposal and efficient conduct of a research trial. Pilot studies strengthen a proposal by providing essential baseline information. A general overview of the purpose of pilot studies is provided here, along with a description of the process of using findings from a pilot study to inform the development of a larger multisite trial. Findings from this pilot study examining the effects of co-bedding on twins and their parents are used to revise the research protocol for a larger multisite trial. These changes, which lead to improvement to the protocol, and the rational for these changes are highlighted.", "To compare the physiological stability and behavioral effects of co-bedding with those of single-bedding premature multiple-gestation infants in incubators as well as the psychological effects on their parents.\n Prospective, randomized, repeated measure.\n Convenience sample of 16 infants and 8 parents in the co-bedded group, and 21 infants and 11 parents in the control group.\n Infants in the study group were co-bedded in incubators.\n Baseline and posttesting for parental state anxiety, maternal attachment, and parental satisfaction measures; infant sleep-wake synchronicity; physiological measures; and stress cue measures during baseline and activity.\n Repeated measures 5 (time) x 2 (group) analysis of variance found significant differences in infant daily weight, feeding amount, and high-activity heart rate. There was no difference in parental state anxiety, maternal attachment, and parental satisfaction scores by group, except for higher baseline parental satisfaction scores in the co-bedded group.\n This research demonstrated the safety of co-bedding multiple-gestation infants in incubators but did not find any significant clinical improvement in infant or parental outcomes with co-bedding. Neonatal intensive-care unit providers should educate staff and parents about the potential benefits of co-bedding and consider developing policies and procedures for co-bedding in both incubators and cribs. Co-bedding of multiple-gestation infants may be provided as an adjunctive developmental care strategy if parents desire this intervention." ]

[ "3794867" ]

[ "Efficacy of thromboresistant umbilical artery catheters in reducing aortic thrombosis and related complications." ]

[ "Previous in vitro and in vivo reports suggest that catheters constructed of polyurethane with heparin bonded to the surface (HB-PU) are less thrombogenic than catheters made of polyvinyl chloride (PVC). A randomized trial sufficiently large (power 80%) to detect a reduction in the incidence of umbilical artery (UA) catheter complications, including aortic thrombus formation, from 45% to 20% was conducted in 125 infants. The infants were monitored for complications possibly related to the use of a UA catheter, such as systemic hypertension and abnormalities of lower extremity perfusion. The presence of aortic thrombi was assessed by ultrasound study 3.5 +/- 1.2 (SD) days and 11.1 +/- 2.3 days after insertion of the catheter. The use of HB-PU umbilical catheters did not lead to a significant reduction in the incidence of complications and aortic thrombi compared with the use of PVC catheters. The lack of reduction may have been related to the prolonged duration of catheter use in both groups. A much larger study would have been required to detect a smaller, but perhaps clinically significant, reduction in catheter-associated complications." ]

[ "19157102", "16797309", "72240", "1490755", "12397048", "15685517", "6772366", "20466680", "7051913", "6357576", "16797395", "6107409", "90217" ]

[ "[Efficacy and safety of vardenafil for kidney transplant recipients with erectile dysfunction].", "Efficacy and safety of vardenafil in renal transplant recipients with erectile dysfunction.", "Reversal of uraemic impotence by zinc.", "Effect of vitamin E therapy on sexual functions of uremic patients in hemodialysis.", "Efficacy of oral sildenafil in hemodialysis patients with erectile dysfunction.", "The efficacy of sildenafil for the treatment of erectile dysfunction in male peritoneal dialysis patients.", "Influence of 1,25 dihydroxycholecalciferol on sexual dysfunction and related endocrine parameters in patiens on maintenance hemodialysis.", "Effects of sildenafil and vardenafil on erectile dysfunction and health-related quality of life in haemodialysis patients: a prospective randomized crossover study.", "Effect of oral zinc therapy on gonadal function in hemodialysis patients. A double-blind study.", "Bromocriptine improves reduced libido and potency in men receiving maintenance hemodialysis.", "Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.", "Absence of a therapeutic effect of zinc in the sexual dysfunction of haemodialysed patients.", "Improved sexual function in male haemodialysis patients on bromocriptine." ]

[ "To evaluate the efficacy and safety of vardenafil in kidney transplant recipients with erectile dysfunction.\n Thirty-nine kidney transplant recipients with erectile dysfunction (ED) and serum creatinine values <2 mg/dl were enrolled in a 4-week randomized, double blind, placebo-controlled study, 19 treated with placebo and 20 with vardenafil. Vardenafil efficacy was assessed with the IIEF questionnaire after 4 weeks of treatment, and its safety appraised by measuring serum creatinine levels, creatinine clearances and cyclosporine concentrations before and after the treatment.\n IIEF scores improved from 12.6 +/- 3.4 to 26.5 +/- 2.8 (P < 0.01), but renal function and cyclosporine concentrations remained unchanged in the vardenafil-treated patients. Adverse effects were observed in 4 patients: headache in 2, palpitation and flush in 1, and dyspepsia in the other.\n Oral vardenafil therapy has a high efficacy and a low incidence of adverse events for kidney transplant recipients with ED.", "Erectile dysfunction (ED) profoundly affects the quality of life. The prevalence of ED in renal transplant recipients is reported by high as 50% to 60%. We evaluated the efficacy and safety of vardenafil in these patients with ED as well as its effects on graft function and on cylosporine or tacrolimus concentrations. Thirty-nine recipients with ED and serum creatinine values<2 mg/dL were treated with vardenafil. ED was assessed using the self-administered International Index of Erectile Function (IIEF). ED was diagnosed by using penile color-Doppler ultrasonography and intracavernosal injection. Vardenafil efficacy was assessed by readministering the IIEF questionnaire after 4 weeks of therapy. Serum creatinine levels, creatinine clearances, and cyclosporine/tacrolimus concentrations were measured before and after vardenafil therapy. Twenty-one recipients with ED served as placebo controls and 15 without ED as another control group. The IIEF scores improved from 12.80+/-3.5 to 26.46+/-2.4 in vardenafil-treated patients with ED (P<.001). Renal function and cyclosporine/tacrolimus concentrations did not change with vardenafil therapy. Side effects were observed in 7 (18%) patients: headache in three, palpitations in one, flushing in two, and dyspepsia in one. This study demonstrated that ED improved with vardenafil in renal transplant recipients with ED. For 4 weeks vardenafil therapy was free of side effects. Renal function tests did not change. Also, no dose change in immunosuppressive drugs was required during 4 weeks of verdanafil therapy.", "In eight impotent haemodialysed men with low plasma-zinc levels sexual function, including potency, frequency of intercourse, libido, and plasma testosterone, follicle-stimulating hormone, and luteinising hormone levels, was determined before and after therapy with zinc (four patients) or placebo (four patients). Dialytic administration of zinc strikingly improved potency in all patients and raised the plasma-testosterone to normal in the two with low pretreatment plasma-testosterone levels. Placebo did not improve sexual function in any patient. Zinc deficiency is a reversible cause of gonadal dysfunction in uraemia.", "Twenty-four uremic patients on hemodialysis who had never been treated with vitamin E or related drugs and 12 control patients with normal renal function were studied. Hemodialysis patients were randomly divided into two groups; 12 were treated with oral vitamin E (300 mg/day) for eight weeks and 12 uremic patients and 12 controls were given placebo. Serum vitamin E, prolactin, FSH, LH, and free testosterone levels were measured in all patients before and after treatment. After the vitamin E treatment serum prolactin levels were significantly decreased (50.8 vs 15.4 ng/ml, p < 0.01). Vitamin E levels were significantly increased (1.11 vs 1.22 mg/dl, p < 0.05). Serum FSH, LH and free testosterone were not affected. In the other two groups there were no significant changes. These results show that vitamin E treatment lowers prolactin levels in uremic hemodialysis patients. This might be due to inhibition of central prolactin secretion. Vitamin E inhibits pituitary gland hypertrophy in vitamin E-deficient rats.", "The aim of this study was to evaluate the efficacy and safety of oral sildenafil to treat erectile dysfunction (ED) in chronic renal failure in patients on hemodialysis (HD). A double-blind, randomized, placebo-controlled study of oral sildenafil (50 mg) administered as required in HD patients with ED was designed. Patients on HD for at least 6 mo and who had a stable relationship with a female sexual partner were included. Patients older than 70 yr with penile anatomic abnormalities, cirrhosis, diabetes, angina, severe anemia, and those who were on nitrate treatment or with a recent history of stroke or myocardial infarction were not included. The International Index of Erectile Dysfunction (IIEF) was employed to evaluate ED and treatment response. Forty-one patients were evaluated (21 received placebo, and 20 sildenafil). Baseline clinical and demographic parameters were similar in both groups. Sildenafil was associated with improvement in the score of all questions and domains of the IIEF, except those related to sexual desire. Using the erectile function domain to evaluate primary efficacy, improvement was observed in 85% of the sildenafil patients compared with 9.5% of placebo patients. Sildenafil use resulted in normal EF scores in 35% of sildenafil patients. Sildenafil was well tolerated. Headaches and flushing occurred in both groups. Dyspepsia was reported by two patients in the sildenafil group. In conclusion, oral sildenafil seems to be an effective and safe treatment for ED in selected patients with chronic renal failure on hemodialysis.", "The aim of this study was to evaluate the safety and effectiveness of sildenafil in male peritoneal dialysis patients with erectile dysfunction.\n Sixteen peritoneal dialysis patients were recruited to this prospective, randomized, double-blind, placebo-controlled, crossover study of sildenafil during a period of 8 weeks. Efficacy was assessed by using the International Index of Erectile Function and a Global Assessment Question. Penile arterial supply was assessed by means of Doppler ultrasound in all patients, and adverse events were recorded.\n Three patients failed to complete the study (1 patient received a renal transplant, 1 patient died unrelated to the study, and 1 patient withdrew for personal reasons). In the remainder, there was a significant improvement in erectile function with sildenafil compared with placebo (P = 0.01) and the baseline assessment (P = 0.002). There were also significant improvements in intercourse satisfaction (P = 0.002) and overall satisfaction (P = 0.005) compared with baseline. In response to the Global Assessment Question, 75% of patients reported improvement in erections. Only 1 adverse event was reported: a headache, which resolved after the third dose of sildenafil.\n Sildenafil caused a significant improvement in erectile function in peritoneal dialysis patients, with a success rate at least as high as that reported in other patient groups. The drug was well tolerated, with few adverse events.", "It has been postulated that hyperparahyroidism is in part responsible for sexual dysfunction in dialyzed patients and that this could improved by 1,25(Oh)2D3. In a single blind study patients on maintenance hemodialysis were treated after a control period with 1,25 (OH)2D3 and with placebo in random order. Sexual performance was assessed with a detailed semistructured psychiatric interview protocol in 14 and several endocrine parameters were analyzed in 15 patients. Under control conditions sexual function was disturbed in 11/14 patients. Plasma testosterone was moderately decreased in men, PRL and PTH levels were distinctly elevated in both sexes. 1,25(OH)2D3 raised serum calcium levels significantly from 9.6 to10.6 mg/100 ml ( P < 0.01) and lowered PTh from 1.39 to 0.82 ng/ml ( P < 0.01). However, no improvement in sexual function (such as libido, frequency of intercourse or masturbation) was found, and apart from a slight rise of testosterone in men and moderate fall of PRl in men and women endocrine parameters remained unchanged. It is concluded that in spite of an improvement of secondary hyperparathyroidism, treatment with 1,25(OH)2D3 for 2 to 4 months was of no value in improving sexual dysfunction in these hemodialysis patients.", "Erectile dysfunction (ED) is prevalent in end-stage renal disease (ESRD) and has been associated with impaired health-related quality of life (HRQoL). HRQoL, in turn, is related to morbidity and mortality in ESRD patients. Previous studies have shown improved HRQoL with ED treatment using sildenafil and vardenafil. However, no study has examined the effects of sildenafil or vardenafil on HRQoL in impotent ESRD patients. Furthermore, vardenafil has never been tested and its safety profile has not been determined in ESRD patients. The aim of this randomized crossover study was to compare the effects of sildenafil and vardenafil on measures of HRQoL and on ED scores as well as to determine the safety profile of vardenafil in ESRD patients.\n In 32 haemodialysis patients with impotence, ED and HRQoL were evaluated by the International Index of Erectile Function (IIEF-5) and the 36-item Short-Form Health (SF-36) surveys, respectively. Patients were randomized into sildenafil and vardenafil groups. After a 4-week treatment and 2-week washout periods, crossover was performed and an additional 4-week treatment was administered. IIEF-5 and SF-36 surveys were given before and after each treatment period. Adverse effects were evaluated by interview. Friedman tests and Bonferroni-adjusted Wilcoxon signed-rank tests were used to compare groups and for post hoc analysis, respectively.\n IIEF-5 and SF-36 scores were significantly improved by both sildenafil and vardenafil compared to pretreatment values. There were no differences between sildenafil and vardenafil with respect to the studied parameters. Adverse effect profiles were also similar. No patient dropped out because of side effects.\n Sildenafil and vardenafil caused similar improvements in ED and HRQoL in haemodialysis patients. Vardenafil was well tolerated in our patient population.", "Zinc deficiency may account for the persistence of gonadal dysfunction in a majority of uremic men despite adequate dialysis. Twenty stable patients having hemodialysis three times a week completed a double-blind trial using either 50 mg of elemental zinc as zinc acetate (10 patients) or placebo (10 patients), orally. At the end of the 6-month study period, a significant increase in the mean (+/- SE) plasma zinc (75 +/- 2 micrograms/dL to 100 +/- 2 micrograms/dL, p less than 0.001), serum testosterone (2.8 +/- 0.3 ng/dL to 5.2 +/- 0.5 ng/mL, p less than 0.001), and sperm count (30 +/- 3 million/mL to 63 +/- 5 million/mL, p less than 0.001) occurred in the zinc-treated group, but not in those receiving the placebo. The zinc-treated group also had a significant fall in serum luteinizing hormone (92 +2- 10 mIU/mL to 49 +/- 26 mIU/mL, p less than 0.005) and follicle stimulating hormone (45 +/- 9 mIU/mL to 25 +/- 7 mIU/mL, p less than 0.05), not seen in the placebo group. Patients receiving zinc had an improvement in potency, libido, and frequency of intercourse not found in the placebo group. These results suggest that zinc deficiency is a reversible cause of gonadal dysfunction in patients having regular hemodialysis.", "Twenty-five men on maintenance hemodialysis commenced a placebo-controlled, double-blind, crossover trial of bromocriptine for erectile impotence. Eight patients on bromocriptine and one on placebo failed to complete the trial due to side-effects and 2 were withdrawn following renal transplantation. Libido or the frequency and/or quality of erections or both improved in 11 of the remaining 14 patients during bromocriptine treatment. A significant (P less than 0.01) improvement in patients' perception of sexual performance occurred on bromocriptine compared with placebo. The 3 patients in whom potency failed to improve had the lowest serum testosterone concentrations. Bromocriptine is usually effective in the management of impotence in males receiving maintenance hemodialysis provided pretreatment serum testosterone is above the lower end of the normal range, but side-effects are relatively common.", "Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients.\n The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?).\n Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P < 0.001) and 4 (maintenance frequency; P < 0.001) was significantly better after sildenafil therapy. There were no significant differences between baseline and post-placebo treatment scores, except for question 13 (relationship satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination.\n Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.", "The effect of zinc therapy and placebo on sexual function and endocrine status was investigated in a double-blind study of 14 male patients with chronic renal failure on regular haemodialysis. Zinc chloride was added to the dialysate of 7 patients for 6 weeks, raising the serum zinc concentration by 17% and placebo was added to the dialysate of the other patients. At the start of the trial 9 patients said they had decreased sexual function. Records of penile erectile activity during sleep confirmed the organic nature of the sexual dysfunction. Plasma testosterone concentrations were low or in the low normal range, basal serum luteinising-hormone levels were raised, and the early luteinising-hormone response to luteinising-hormone-releasing hormone was exaggerated, suggesting primary testicular failure. Zinc administration had no significant effect on any aspect of sexual function assessed by questionnaire or nocturnal penile tumescence monitoring. Plasma testosterone and basal and stimulated gonadotrophin levels were also unaltered by zinc administration.", "The effect of bromocriptine on sexual activity was studied in male haemodialysis patients in a single-blind placebo controlled trial with random cross-over. At a dose of 2.5 mg bromocriptine twice day, plasma-prolactin concentrations were consistently reduced, while sexual function as assessed by a questionnaire was markedly improved. At the doses used, side-effects, particularly hypotension, were common, but bromocriptine helped to restore sexual function in dialysed patients." ]

[ "1362432", "15376564", "11236267", "2492252", "9391254", "9833916", "7913907", "10960437", "10690604", "11100339", "10831267" ]

[ "A prospective randomised controlled trial comparing the efficacy of somatostatin with injection sclerotherapy in the control of bleeding oesophageal varices.", "[Octreotide administration and/or endoscopic treatment in cirrhotic patients with acute variceal bleeding: a multicentric study].", "[Sclerotherapy versus somatostatin in the treatment of upper digestive hemorrhage caused by rupture of esophageal varices].", "Controlled clinical trial of injection sclerotherapy for active variceal bleeding.", "A multicentre randomised trial comparing octreotide and injection sclerotherapy in the management and outcome of acute variceal haemorrhage.", "Randomized controlled trial of sclerotherapy versus somatostatin infusion in the prevention of early rebleeding following acute variceal hemorrhage in patients with cirrhosis. Variceal Bleeding Study Group.", "A prospective randomized trial comparing somatostatin and sclerotherapy in the treatment of acute variceal bleeding.", "Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study.", "A prospective randomized trial from Turkey comparing octreotide versus injection sclerotherapy in acute variceal bleeding.", "Octreotide in acute bleeding esophageal varices: a prospective randomized study.", "Efficacy of octreotide and sclerotherapy in the treatment of acute variceal bleeding in cirrhotic patients. A prospective, multicentric, and randomized clinical trial." ]

[ "Since previous reports have suggested that somatostatin may be of value in the control of acute variceal haemorrhage, we compared its efficacy with that of injection sclerotherapy in a randomised controlled clinical trial. Eighty consecutive patients with endoscopically-proven severe variceal bleeding were randomised to injection sclerotherapy (n = 41) or somatostatin (n = 39) given as a continuous infusion of 250 micrograms/h for 5 days plus daily bolus administration of 250 micrograms. The efficacy of injection sclerotherapy and somatostatin infusion in controlling haemorrhage and preventing rebleeding (censored at 5 days), mortality (censored at 28 days) and complications was compared. The aetiology of the portal hypertension and transfusion requirements was similar between the two groups, but there were more patients with severe liver disease (Child's C) in the somatostatin group. There was no significant difference between the two treatments in the initial (p = 1.0) or overall control of bleeding (p = 0.58). Furthermore, somatostatin was as effective as injection sclerotherapy in controlling bleeding in patients with severe liver disease or in those actively bleeding at the time of their endoscopy. The relative risk of rebleeding whilst receiving somatostatin compared to injection sclerotherapy was 1.39 [95% Confidence Interval (CI) 3.73; 0.52], but this was reduced to 0.98 (95% CI 0.37; 2.67) when readjusted for Child's grading, the only prognostic factor shown to be of significance. Mortality was not significantly different between the two groups of patients (p = 0.31). The relative risk of dying whilst receiving somatostatin compared to injection sclerotherapy was 1.6 (95% CI 3.93; 0.66) but was reduced to 1.03 (95% CI 0.47; 2.47) when adjusted for Child's grading, the only significant prognostic factor. Complications in the somatostatin group were minor and less frequent than after injection sclerotherapy. The results of this study indicate that somatostatin is a safe treatment, which is as effective an endoscopic injection sclerotherapy for acute variceal bleeding.", "Acute variceal bleeding in cirrhotic patients is an emergency with a high risk of rebleeding and death. Endoscopic procedures such as sclerotherapy or banding, combined or not with drugs such as octreotide could be considered.\n To assess the value of octreotide in the control of acute variceal bleeding.\n Ninety-two patients were randomized into three groups: endoscopic therapy plus octreotide 50 microg/h bolus and continuous infusion for 5 days (n=36); octreotide (same dosage) (n=13) and endoscopic therapy only (banding and/or sclerotherapy) (n=43).\n Haemostasis at 24 hours was achieved in 97% of patients with combined treatment, 69% of patients receiving octreotide, and 93% of patients with endoscopic therapy (p=0.2). Three patients with combined treatment, four patients receiving octreotide and eight patients with endoscopic therapy, rebled during the first five days (p=0.15). The mean of blood units transfused was similar in the three groups. No differences were observed in hospital days and side effects. At 42 days of follow up, eight patients with endoscopic therapy, one patients with combined therapy and 2 patients receiving octreotide, died (p=NS).\n Octreotide is useful in the management of acute variceal bleeding. The absence of important side effects, renders it as a safe adjuvant treatment associated with endoscopic treatment.", "The aim of this study was to compare the efficacy of somatostatin versus endoscopic sclerotherapy in the management of digestive bleeding caused by rupture of esophageal varices. Forty patients were evaluated; 21 were randomly assigned to receive somatostatin (initial 250 micrograms followed by a 48-hour continuous infusion of 250 micrograms/h and 250 micrograms 6/6 h bolus in the first 24 hours) and 19 to receive endoscopic sclerotherapy with ethanolamine oleate 5%. The patients were evaluated after 48 hours and after 7 days of treatment. Both groups of patients were similar in sex, age, gravity of the hemorrhage and liver dysfunction. Therapeutic failure occurred in 26.3% and 35.7% in the group of endoscopic sclerotherapy (48 h and 7 days respectively), and in 23.8% and 21.4% in the group of somatostatin. The need of blood transfusion (3.38 U in the group of endoscopic sclerotherapy and 2.42 U in the group of somatostatin) and the mortality rate (31.6% in the group of endoscopic sclerotherapy and 28.6% in the group of somatostatin) were also similar (P > 0.05). The authors conclude that somatostatin is as effective as endoscopic sclerotherapy and that it should be considered in the treatment of acute esophageal variceal bleeding.", "In a prospective, randomized clinical trial, immediate injection sclerotherapy was compared with treatment by a combined infusion of vasopressin (0.4 unit per min) and nitroglycerin (40 to 400 micrograms per min) in 50 consecutive patients with 64 episodes of endoscopy-proven variceal hemorrhage. Control of bleeding was assessed over a 12-hr period following entry into the trial. Patients in the vasopressin + nitroglycerin group were then treated by sclerotherapy, as were those in the sclerotherapy group who continued to bleed. At 12 hr, bleeding was controlled in 29 (88%) of the 33 episodes treated by sclerotherapy compared with 20 (65%) of 31 episodes treated by vasopressin + nitroglycerin (p less than 0.05). Recurrence of variceal bleeding occurred at the same frequency (31%). Although admission mortality was less in those initially treated by sclerotherapy compared to those managed by vasopressin + nitroglycerin, this did not reach statistical significance (27 and 39%, respectively, p greater than 0.20). Sclerotherapy carried out as the first treatment of the active variceal hemorrhage proved both safe and effective, even in the presence of major hemorrhage, and as compared to combined vasopressin and nitroglycerin it proved superior.", "Few studies have compared vasoactive drugs with endoscopic sclerotherapy in the control of acute variceal haemorrhage. Octreotide is widely used for this purpose, but its value remains undetermined.\n To compare octreotide with endoscopic sclerotherapy for acute variceal haemorrhage.\n Consecutive patients with acute variceal haemorrhage.\n Patients were randomised at endoscopy to receive either a 48 hour intravenous infusion of 50 pg/h octreotide (n = 73), or emergency sclerotherapy (n = 77).\n Overall control of bleeding and mortality was not significantly different between octreotide (85%, 62 patients) and sclerotherapy (82%, 63 patients) over the 48 hour trial period (relative risk of rebleeding 0.83; 95% confidence interval (CI) 0.38 to 1.82), irrespective of Child's grading or active bleeding at endoscopy. One major complication was observed in the sclerotherapy group (aspiration) and two in the octreotide group (pulmonary oedema, severe paralytic ileus). During 60 days of follow up there was an overall trend towards an increased mortality in the octreotide group which was not statistically significant (relative risk of dying at 60 days 1.91, 95% CI 0.97 to 3.78, p = 0.06).\n The results of this study indicate that intravenous octreotide is as effective as injection sclerotherapy in the control of acute variceal bleeding, but further controlled trials are necessary to evaluate the safety of this treatment.", "Early rebleeding is a very frequent complication of variceal hemorrhage. Sclerotherapy effectively controls variceal hemorrhage and prevents early rebleeding. Somatostatin infusion is as effective as sclerotherapy in controlling variceal hemorrhage, but no study has evaluated the efficacy of 5-day somatostatin infusion in preventing early rebleeding after the initial control of bleeding. The aim of the study was to compare the efficacy and safety of somatostatin and sclerotherapy in the prevention of early variceal rebleeding in cirrhotic patients.\n The study included 169 patients with acute variceal hemorrhage who were randomized within 24 h of controlling the acute bleeding to receive either sclerotherapy (n=79) or continuous somatostatin infusion for 5 days (250 microg/h after a 250-microg bolus, repeated every 24 h, n=90). Success of therapy was defined by absence of rebleeding during the 5 days following randomization.\n Early (5 days) rebleeding occurred in 12/79 patients treated with sclerotherapy vs 14/90 of those receiving somatostatin (NS). The treatment was equally effective in Child's C patients (sclerotherapy: 18/20; somatostatin: 17/20; NS) and Child's A+B patients (sclerotherapy: 49/59; somatostatin: 59/70; NS). Complications occurred in 19/79 patients receiving sclerotherapy vs 4/90 in the somatostatin group (p= 0.00019), being severe in 6 vs 0 patients (p=0.0094). There were no differences between the two groups in the incidence of 6-week rebleeding (14% vs 15%, NS) and mortality (9% vs 9%).\n Continuous somatostatin infusion is as effective as sclerotherapy in preventing early variceal rebleeding and maintaining low mortality following acute variceal hemorrhage. Somatostatin is associated with a lower rate of complications than sclerotherapy.", "Somatostatin and endoscopic sclerotherapy are widely used in the treatment of acute variceal bleeding. Although objective evidence does exist about the advantages of either treatment, data comparing both procedures are scarce. In order to compare the effectiveness and safety of somatostatin and sclerotherapy in the treatment of acute variceal bleeding, 70 consecutive cirrhotic patients suffering from esophageal variceal hemorrhage and meeting the inclusion criteria were randomly assigned to treatment with somatostatin (35 patients) or sclerotherapy (35 patients). No differences in age, sex, alcohol intake, etiology of cirrhosis and severity of liver failure were found between groups. Failure of treatment (defined as persistence of bleeding despite therapy or subsequent rebleeding within the 48-hr trial period) occurred in seven patients (20%) in the somatostatin group and in six (17.1%) in the sclerotherapy group (NS). Early rebleeding occurred in seven of 28 patients (25%) in the somatostatin group and in five of 29 (17.2%) in the sclerotherapy group (NS). Mortality within the first 6 wk was no different between both groups: 10 (28.5%) and eight (22.8%) in the somatostatin and sclerotherapy groups, respectively. Sclerotherapy, but not somatostatin, was associated with major complications in five cases (14.2%) (p = 0.026), two of which resulted in patient's death. These results suggest that somatostatin is safer, and as effective as sclerotherapy, in controlling acute variceal bleeding until an elective treatment can be established.", "Failure to control bleeding and early rebleeding account for the high mortality associated with variceal hemorrhage in cirrhosis. We compared endoscopic sclerotherapy to terlipressin, a drug that effectively controls acute bleeding while reducing in-hospital mortality. This multicenter randomized controlled trial included 219 cirrhotic patients admitted for endoscopy-proven acute variceal bleeding and randomized to receive repeated injections of terlipressin during 6 days (n = 105) or emergency sclerotherapy (n = 114). Success was defined as obtaining control of bleeding (24-hour bleeding-free period during the first 48 hours) and lack of early rebleeding (any further bleeding from initial control to 5 days later) and survival during the study. Both groups were similar at inclusion. Failure rate for terlipressin was 33% and 32% for sclerotherapy (not significant [NS]). Early rebleeding was responsible for 43% and 44% of failures, respectively. This high efficacy was observed in both Child-Pugh class A + B and Child-Pugh class C patients. Both treatments were similar regarding transfusion requirements, in-hospital stay, and 6-week mortality (26 vs. 19 patients). Side effects appeared in 20% of patients receiving terlipressin and in 30% of those on sclerotherapy (P =.06); being serious in 4% and 7%, respectively (NS). In conclusion, terlipressin and sclerotherapy are equally highly effective therapies achieving the initial control of variceal bleeding and preventing early rebleeding. Both treatments are safe, but terlipressin is better tolerated. Therefore, terlipressin may represent a first-line treatment in acute variceal bleeding until the administration of elective therapy, especially in hospitals where a skilled endoscopist is not available 24 hours a day.", "Bleeding from gastroesophageal varices continues to be a life threatening complication of chronic liver diseases and portal hypertension. The purpose of this randomized prospective study is to compare the efficacy of octreotide administration and emergency injection sclerotherapy for the control of actively bleeding esophageal varices and prevention of early rebleeding in patients with cirrhosis.\n A total of 66 episodes of endoscopically proven active variceal bleeding in 52 patients were included in this study. Following admission to the hospital, the patients were resuscitated with blood and plasma, and fiberoptic endoscopy was performed within 2 hours. Thirty-six bleeds in 28 patients and 30 bleeds in 24 patients were randomized to endoscopic variceal sclerotherapy (1% polidocanol) and to octreotide infusion (at 50 micrograms/h for 12 hours following the initial 50 micrograms i.v. bolus), respectively.\n Bleeding was initially controlled within 6 hours in 75% of episodes by endoscopic variceal sclerotherapy and in 73.3 by octreotide infusion (P > 0.05). There were no significant differences between the 2 groups in early rebleeding (within 72 hours of randomization) (22% vs. 22.7%), blood transfusion (4.2 +/- 1.8 units vs. 4.8 +/- 2.9 units), or hospital mortality (3.6% vs. 3.3%). Treatment failed in 9 episodes (25%) in the sclerotherapy group and in 8 episodes (26.7%) in the octreotide group.\n We consider that Octreotide would appear to be as effective as sclerotherapy in both the early control of variceal hemorrhage and in the prevention of early recurrent bleeding and should therefore be considered the treatment of choice in those centers where 24-hour endoscopy is not available. Furthermore, even in hospitals that do have a 24-hour endoscopy service there is good evidence that octreotide therapy should be commenced as soon as a patient enters hospital with a suspected variceal bleed to achieve rapid homeostasis. When initial hemostasis is achieved, elective endoscopic therapies can be undertaken with greater success.", "To assess the value of octreotide in the control of acute bleeding esophageal varices, in a prospective randomized study.\n One hundred and ninety-seven patients admitted for variceal bleeding confirmed at endoscopy were recruited and divided into two groups: group I (n = 111) with endoscopic stigmata of recent bleeding; and group II (n = 86) with active bleeding at emergency endoscopy. Patients in group I were randomized to receive a continuous infusion of octreotide (n = 58) or emergency sclerotherapy (n = 53). Patients in group II were assigned to sclerotherapy (n = 42) or to sclerotherapy plus octreotide (n = 44). At the end of the period of study (48 hours), patients were submitted to sclerotherapy or band ligation until variceal obliteration was achieved.\n In group I, octreotide was found to be as effective as sclerotherapy regarding hemostasis at 48 hours and on day 7 after the index bleeding episode. Transfusion needs were not significantly different for the two treatment modalities. In group II, the association of octreotide with sclerotherapy was significantly better than sclerotherapy alone either in controlling acute active bleeding (P < 0.001) or in achieving hemostasis at 48 hours (P < 0.01). Transfusion needs were significantly fewer in patients treated with this therapeutic association as compared to sclerotherapy alone.\n These results suggest that octreotide infusion is effective in the treatment of variceal bleeding. In patients with recent bleeding, octreotide infusion is as effective as emergency sclerotherapy. In active variceal bleeding, it is a valuable adjuvant treatment in association with emergency sclerotherapy.", "Sclerotherapy is the most widely used method for treatment of acute variceal bleeding. Previous reports have suggested that octreotide infusion is as effective as sclerotherapy. Our aim was to investigate the efficacy and safety of octreotide in comparison with sclerotherapy in controlling variceal bleeding.\n Seventy-six cirrhotic patients were randomized to receive either sclerotherapy (n = 37) or octreotide (n = 39) infusion of 50 microg/h intravenously for 48 h after a bolus of 100 microg, followed by subcutaneous injection of 100 microg/8 h for an additional 72 h.\n The two groups were similar in base-line data. A similar initial control of bleeding was obtained in 94.6% for sclerotherapy and 84.6% for octreotide (NS). No difference was observed between sclerotherapy and octreotide in rebleeding (23% versus 33%) and treatment failure (22% versus 36%, respectively). Furthermore, the overall success of treatment was 78% for sclerotherapy and 64% for octreotide. No significant difference in mortality was observed between treatments (eight patients for octreotide and three patients for sclerotherapy, NS).\n These results show that both treatments present a very high and similar initial and final control of bleeding. However, there is a trend that could be clinically important towards better results in the patients treated with sclerotherapy." ]

[ "18055721", "9093249", "8476829", "9240590", "7772106", "1760601", "12548189" ]

[ "Hysterectomy compared with endometrial ablation for dysfunctional uterine bleeding: a randomized controlled trial.", "Medical Research Council randomised trial of endometrial resection versus hysterectomy in management of menorrhagia.", "Randomised controlled trial comparing endometrial resection with abdominal hysterectomy for the surgical treatment of menorrhagia.", "Endometrial resection versus vaginal hysterectomy for menorrhagia: long-term clinical and quality-of-life outcomes.", "Randomised trial of hysterectomy, endometrial laser ablation, and transcervical endometrial resection for dysfunctional uterine bleeding.", "A randomised trial comparing endometrial resection and abdominal hysterectomy for the treatment of menorrhagia.", "Hysteroscopic endometrial resection versus laparoscopic supracervical hysterectomy for menorrhagia: a prospective randomized trial." ]

[ "To compare the effectiveness of hysterectomy and endometrial ablation in women with dysfunctional uterine bleeding.\n The Surgical Treatments Outcomes Project for Dysfunctional Uterine Bleeding was a multicenter, randomized controlled trial. Eligible women were premenopausal with dysfunctional uterine bleeding and aged 18 years or older. Primary outcomes were problems that led the woman to seek care solved, bleeding, pain, and fatigue at 12 months. Additional outcomes included quality of life, adverse events, reoperation, and others at 24 months and up to 5 years.\n We randomly assigned 237 women between January 1998 and June 2001. Follow-up ended in June 2003. We completed 24 months of follow-up on 114 of 123 women assigned to endometrial ablation and 111 of 114 assigned to hysterectomy. Approximately 85% of women were aged younger than 45 years; 76.4% classified themselves as white, 18.6% as African American, less than 1% as Asian, 4.6% as American Indian, and 8.4% as Hispanic (classification within more than one category possible). Both endometrial ablation and hysterectomy were effective at 24 months in solving the problem that led women to seek care (84.9% compared with 94.4%), and in relieving bleeding, pain, fatigue, and other symptoms, although hysterectomy was more effective for bleeding. By 48 months, 32 of the 110 women initially receiving endometrial ablation required reoperation. Adverse events were more frequent with hysterectomy.\n Both endometrial ablation and hysterectomy are effective treatments in women with dysfunctional uterine bleeding. Hysterectomy (as the index surgery) was associated with more adverse events and a substantial number of patients receiving endometrial ablation had reoperation.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00114088\n I.", "The most frequent indication for hysterectomy is menorrhagia, even though the uterus is normal in a large number of patients. Transcervical resection of the endometrium (TCRE) is a less drastic alternative, but success rates have varied and menorrhagia can recur. We have tested the hypothesis that the difference in the proportion of women dissatisfied and requiring further surgery within 3 years of TCRE or hysterectomy would be no more than 15%.\n 202 women with symptomatic menorrhagia were recruited to a multicentre, randomised, controlled trial to compare the two interventions. TCRE and hysterectomy were randomly assigned in a ratio of two to one. The primary endpoints were women's satisfaction and need for further surgery. The patients' psychological and social states were monitored before surgery, then annually with a questionnaire. Analysis was by intention to treat.\n Data were available for 172 women (56 hysterectomy, 116 TCRE); 26 withdrew before surgery and four were lost to follow-up. Satisfaction scores were higher for hysterectomy than for TCRE throughout follow-up (median 2 years), but the differences were not significant (at 3 years 27 [96%] of 28 in hysterectomy group vs 46 [85%] of 54 in TCRE group were satisfied; p = 0.16). 25 (22%) women in the TCRE group and five (9%) in the hysterectomy group required further surgery (relative risk 0.46 [95% CI 0.2-1.1], p = 0.053). TCRE had the benefits of shorter operating time, fewer complications, and faster rates of recovery.\n TCRE is an acceptable alternative to hysterectomy in the treatment of menorrhagia for many women with no other serious disorders.", "To evaluate the effectiveness of endometrial resection as a surgical treatment for menorrhagia.\n Randomised controlled trial.\n Gynaecology department at a teaching hospital.\n Two hundred women needing surgical treatment for menorrhagia between January 1990 and May 1991. After withdrawal of four women 97 underwent hysterectomy and 99 underwent endometrial resection.\n Patient satisfaction 4 months after surgery; post-operative complications; length of hospital stay; duration of time before return to work, normal daily activities and sexual intercourse; change in premenstrual symptoms.\n The difference in patient satisfaction between endometrial resection (84 out of 99) and abdominal hysterectomy (89 out of 95) just reached statistical significance in favour of abdominal hysterectomy at 4 months after surgery (difference = 9%, 95% confidence intervals (CI) 1.1%-17.5%). Post-operative morbidity, length of hospital stay and time taken to return to work, normal daily activities and sexual intercourse were significantly less in the endometrial resection group. However, the premenstrual symptoms of dysmenorrhoea, bloating and breast tenderness were less frequent after hysterectomy.\n In the short term, endometrial resection was almost as satisfactory as abdominal hysterectomy for the surgical treatment of menorrhagia, and was associated with less morbidity. However, even at 4 months after surgery, there was a failure rate of at least 10% in those in whom endometrial resection appeared complete. Longer term comparative studies are necessary before the widespread introduction of endometrial resection as an alternative to abdominal hysterectomy for the surgical treatment of menorrhagia.", "Our purpose was to compare patients' satisfaction with the effect of treatment, health-related quality of life, psychologic status, and sexual functioning 2 years after endometrial resection or vaginal hysterectomy for menorrhagia.\n Menorrhagic women < or = 50 years old with a mobile uterus smaller than a 12-week pregnancy were enrolled in a randomized trial to compare endometrial resection and vaginal hysterectomy. Two years after surgery the women were requested to rate the degree of satisfaction with the effect of the operation and to complete the Short Form 36 general health survey questionnaire, the Hospital Anxiety and Depression Scale, and the revised Sabbatsberg Sexual Rating Scale.\n Forty-one subjects underwent endometrial resection and 44 underwent vaginal hysterectomy without major complications. Of the 77 women attending the 2-year follow-up visit, 33 of 38 (86.8%) in the endometrial resection arm were very satisfied or satisfied with the treatment compared with 37 of 39 (94.8%) of those in the hysterectomy arm. According to the Short Form 36 questionnaire, social functioning and vitality scores were significantly better in the hysterectomy group than in the resection group. Significantly lower Hospital Anxiety and Depression Scale anxiety scores were observed in the former than in the latter subjects. The Sabbatsberg Sexual Rating Scale scores were similar in the two groups.\n In patients requiring surgical treatment for menorrhagia vaginal hysterectomy appeared slightly more satisfying and offered a better health-related quality of life than did endometrial resection at 2-year follow-up. Hysterectomy did not adversely affect psychologic status and sexual functioning.", "To evaluate the effectiveness and safety of endometrial laser ablation and transcervical resection of the endometrium compared with hysterectomy in the surgical treatment of women with dysfunctional uterine bleeding.\n Prospective randomised controlled trial.\n Gynaecology department of a large teaching hospital.\n 204 women who would otherwise have been undergoing hysterectomy for menorrhagia were recruited between August 1990 and March 1992 and randomly allocated to hysterectomy (n = 99) or conservative (hysteroscopic) surgery (transcervical resection (n = 52) and laser ablation (n = 53)).\n Operative complications, postoperative recovery, relief of menstrual and other symptoms, patient satisfaction with treatment after six and 12 months.\n Women treated by hysteroscopic surgery had less early morbidity and a significantly shorter recovery period than those treated by hysterectomy (median time to full recovery 2-4 weeks v 2-3 months, P < 0.001). Twelve months later 17 women in the hysteroscopy group had had a hysterectomy, 11 for continuing symptoms; 11 women had had a repeat hysteroscopic procedure; 45 were amenorrhoeic or had only a brown discharge; and 35 had light periods. Dysmenorrhoea and premenstrual symptoms improved in most women in both groups. After 12 months 89% (79/89) in the hysterectomy group and 78% (75/96) in the hysteroscopy group were very satisfied with the effect of surgery (P < 0.05); 95% (85/89) and 90% (86/96) thought that there had been an acceptable improvement in symptoms, and 72% (64/89) and 71% (68/96) would recommend the same operation to others.\n Hysteroscopic endometrial ablation was superior to hysterectomy in terms of operative complications and postoperative recovery. Satisfaction after hysterectomy was significantly higher, but between 70% and 90% of the women were satisfied with the outcome of hysteroscopic surgery. Hysteroscopic surgery can be recommended as an alternative to hysterectomy for dysfunctional uterine bleeding.", "To determine the advantages and disadvantages of endometrial resection and abdominal hysterectomy for the surgical treatment of women with menorrhagia.\n Randomised study of two treatment groups with a minimum follow up of nine months.\n Royal Berkshire Hospital, Reading.\n 51 of 78 menorrhagic women without pelvic pathology who were on the waiting list for abdominal hysterectomy.\n Endometrial resection or abdominal hysterectomy (according to randomisation). Endometrial resections were performed by an experienced hysteroscopic surgeon; hysterectomies were performed by two other gynaecological surgeons.\n Length of operating time, hospitalisation, recovery; cost of surgery; short term results of endometrial resection.\n Operating time was shorter for endometrial resection (median 30 (range 20-47) minutes) than for hysterectomy (50 (39-74) minutes). The hospital stay for endometrial resection (median 1 (range 1-3) days) was less than for hysterectomy (7 (5-12) days). Recovery after endometrial resection (median 16 (range 5-62) days) was shorter than after hysterectomy (58 (11-125) days). The cost was 407 pounds for endometrial resection and 1270 pounds for abdominal hysterectomy. Four women (16%) who did not have an acceptable improvement in symptoms after endometrial resection had repeat resections. No woman has required hysterectomy during a mean follow up of one year.\n For women with menorrhagia who have no pelvic pathology endometrial resection is a useful alternative to abdominal hysterectomy, with many short term benefits. Larger numbers and a longer follow up are needed to estimate the incidence of complications and the long term efficacy of endometrial resection.", "This study was undertaken to compare the relative efficacy and safety of hysteroscopic endometrial resection and laparoscopic supracervical hysterectomy in the treatment of abnormal uterine bleeding.\n One hundred eighty-one patients affected by menometrorrhagia and unresponsive to medical treatment agreed to be randomized to either laparoscopic supracervical hysterectomy or hysteroscopic endometrial ablation. They were monitored for 2 years to evaluate perioperative and postoperative outcomes, resolution of symptoms, and patient satisfaction.\n Duration of hospitalization, period of convalescence, perioperative complications, and resumption of normal activity were similar between the two groups. Operative time was significantly shorter in the hysteroscopic group, but patient satisfaction was significantly higher in the laparoscopic group.\n For the treatment of menorrhagia, hysterectomy has the distinct advantage of being curative but the disadvantage of being more invasive than the hysteroscopic approach. However, laparoscopic supracervical hysterectomy preserves the curative effect of hysterectomy without its increased surgical invasiveness, as suggested by the current study." ]

[ "11948381", "12687595", "11158452" ]

[ "A randomized trial of inhaled versus intravenous steroids in ventilator-dependent preterm infants.", "Randomized controlled trial of three different doses of aerosol beclomethasone versus systemic dexamethasone to promote extubation in ventilated premature infants.", "A multicenter, randomized open study of early corticosteroid treatment (OSECT) in preterm infants with respiratory illness: comparison of early and late treatment and of dexamethasone and inhaled budesonide." ]

[ "Intravenous steroids improve the respiratory course in ventilator-dependent preterm infants but have adverse effects. We hypothesized that inhaled steroids would be as effective, but with less systemic effects.\n We conducted a randomized, prospective trial comparing inhaled beclomethasone, either 400 or 800 microg/d, to intravenous dexamethasone in preterm infants dependent on conventional mechanical ventilation and supplemental oxygen at 2 weeks of age.\n Seventy-eight infants were randomized. By day three of therapy, the intravenous steroid group had significantly decreased ventilator and oxygen requirements compared to either inhaled group. The inhaled 800-microg/d group trended toward more rapid decreases in ventilator and oxygen requirements than the 400-microg/d group. By day 14, all groups had similar reductions in ventilator and oxygen requirements. The incidence of adverse effects did not differ between groups.\n In this small, randomized study, inhaled steroids conferred no advantages to intravenous steroids in the management of ventilator-dependent preterm infants.", "Our objective was to determine the safety and efficacy of aerosol beclomethasone vs. systemic dexamethasone for extubation in premature infants at high risk for chronic lung disease (CLD). Intubated preterm infants who were identified as being at high risk for moderate-severe CLD on day 14 of life were randomized to one of four groups. The control group received systemic dexamethasone and aerosol placebo, while the other three groups received either high (2.40-3.69 microg/kg/day delivered to lungs), medium (1.0-1.85 microg/kg/day), or low (0.48-0.74 microg/kg/day) dose aerosol beclomethasone and systemic placebo. Those receiving aerosol steroids who remained ventilator-dependent after 7 days were switched to standard 42-day tapering doses of systemic dexamethasone. The primary outcome was extubation within 1 week of starting steroids, using predefined criteria. Secondary variables included changes in lung function, rates of side effects, and tracheal aspirate white blood cell counts. Sixty-one infants with birth weights of 761 +/- 18 g (mean +/- SEM) and gestational ages of 25.7 +/- 0.2 weeks were randomized to one of the four groups. Seven of 15 infants in the control systemic dexamethasone group were successfully extubated compared with 3/16 in the high-dose beclomethasone group, 1/15 in the medium-dose group, and 2/15 in the low-dose group (P < 0.01). Only dexamethasone subjects demonstrated improvements in lung function over the study period. These infants also had significant increases in blood pressure and blood glucose levels, as well as a decline in their tracheal aspirate white blood cell count. In conclusion, aerosol beclomethasone at the very low doses used in this study did not facilitate extubation in intubated premature infants at high risk for moderate-severe CLD.\n Copyright 2003 Wiley-Liss, Inc.", "To compare early (<3 days) with late (>15 days) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease.\n Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age <30 weeks, postnatal age <72 hours, and need for mechanical ventilation and inspired oxygen concentration >30%. Infants were randomly allocated to 1 of 4 treatment groups in a factorial design: early (<72 hours) dexamethasone, early budesonide, delayed selective (>15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 microg/kg twice daily for 12 days. Delayed selective treatment was started if infants needed mechanical ventilation and >30% oxygen for >15 days. The factorial design allowed 2 major comparisons: early versus late treatment and systemic dexamethasone versus inhaled budesonide. The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis. Secondary outcome measures included death or major cerebral abnormality, duration of oxygen treatment, and complications of prematurity. Adverse effects were also monitored daily.\n There were no significant differences among the groups for the primary outcome. Early steroid treatment was associated with a lower primary outcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18) but even after adjustment for confounding variables the difference remained nonsignificant. Dexamethasone-treated infants also had a lower primary outcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remained not significant after adjustment. For death before discharge, dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 after adjustment, respectively) with the results not quite reaching significance. Duration of supplementary oxygen was shorter in the early dexamethasone group (median: 31 days vs 40-44 days). Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no difference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyperglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance.\n Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide, respectively, but results for survival to discharge were in the opposite direction; however, none of these findings attained statistical significance. Early dexamethasone treatment reduced the risk of persistent ductus arteriosus. Inhaled budesonide may be safer than dexamethasone, but there is no clear evidence that it is more or less effective." ]

[ "15925877", "9445320", "10591382", "17702958" ]

[ "Results of a multicentre, randomised controlled trial of intra-arterial urokinase in the treatment of acute posterior circulation ischaemic stroke.", "PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in Acute Cerebral Thromboembolism.", "Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism.", "Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke: the middle cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan." ]

[ "Patients with ischaemic stroke due to occlusion of the basilar or vertebral arteries may develop a rapid deterioration in neurological status leading to coma and often to death. While intra-arterial thrombolysis may be used in this context, no randomised controlled data exist to support its safety or efficacy.\n Randomised controlled trial of intra-arterial urokinase within 24 h of symptom onset in patients with stroke and angiographic evidence of posterior circulation vascular occlusion.\n Sixteen patients were randomised, and there was some imbalance between groups, with more severe strokes occurring in the treatment arm. A good outcome was observed in 4 of 8 patients who received intra-arterial urokinase compared with 1 of 8 patients in the control group.\n These results support the need for a large-scale study to establish the efficacy of intra-arterial thrombolysis for acute basilar artery occlusion.\n Copyright 2005 S. Karger AG, Basel.", "To test the safety and recanalization efficacy of intra-arterial local delivery of plasminogen activators in acute ischemic stroke, a randomized trial of recombinant pro-urokinase (rpro-UK) versus placebo was undertaken in patients with angiographically documented proximal middle cerebral artery occlusion.\n After exclusion of intracranial hemorrhage by CT scan, patients with abrupt onset of symptoms of focal ischemia likely to receive treatment within 6 hours who satisfied all clinical eligibility criteria underwent carotid angiography. Patients displaying Thrombolysis in Acute Myocardial Infarction grade 0 or 1 occlusion of the M1 or M2 middle cerebral artery were randomized 2:1 to receive rpro-UK (6 mg) or placebo over 120 minutes into the proximal thrombus face. All patients received intravenous heparin. Recanalization efficacy was assessed at the end of the 2-hour infusion, and intracerebral hemorrhage causing neurological deterioration was assessed at 24 hours.\n Of 105 patients who underwent angiography, 59 were excluded from randomization. Among the 46 patients randomized, 40 were treated with rpro-UK (n=26) or placebo (n=14) a median of 5.5 hours from symptom onset. Recanalization was significantly associated with rpro-UK (2P=.017). Hemorrhagic transformation causing neurological deterioration within 24 hours of treatment occurred in 15.4% of the rpro-UK-treated patients and 7.1% of the placebo-treated patients (2P=.64). Both recanalization and hemorrhage frequencies were influenced by heparin dose.\n Intra-arterial local rpro-UK infusion was associated with superior recanalization in acute thrombotic/ thromboembolic stroke compared with placebo. In this regimen, heparin dose influenced hemorrhage frequency and recanalization. Although symptomatic hemorrhage remains a concern, this study suggests that recanalization is enhanced with rpro-UK and heparin.", "Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset, but many patients present later after stroke onset and alternative treatments are needed.\n To determine the clinical efficacy and safety of intra-arterial (IA) recombinant prourokinase (r-proUK) in patients with acute stroke of less than 6 hours' duration caused by middle cerebral artery (MCA) occlusion.\n PROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized, controlled, multicenter, open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998.\n Fifty-four centers in the United States and Canada.\n A total of 180 patients with acute ischemic stroke of less than 6 hours' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infarction signs on computed tomographic scan.\n Patients were randomized to receive 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59).\n The primary outcome, analyzed by intention-to-treat, was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less. Secondary outcomes included MCA recanalization, the frequency of intracranial hemorrhage with neurological deterioration, and mortality.\n For the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = .04). Mortality was 25% for the r-proUK group and 27% for the control group. The recanalization rate was 66% for the r-proUK group and 18% for the control group (P<.001). Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of control patients (P = .06).\n Despite an increased frequency of early symptomatic intracranial hemorrhage, treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days.", "The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan was organized to determine the safety and clinical efficacy of intraarterial infusion of urokinase (UK) in patients with stroke within 6 hours of onset.\n Patients with ischemic stroke presenting within 6 hours of onset and displaying occlusions of the M1 or M2 portion of the middle cerebral artery on carotid angiography were randomized to the UK or control groups. Clinical outcome was assessed by the modified Rankin Scale, National Institutes of Health Stroke Scale, and Barthel Index.\n The Independent Monitoring Committee recommended stopping the trial after approval of intravenous infusion of recombinant tissue plasminogen activator in Japan. A total of 114 patients underwent randomization, 57 patients in each group. Background characteristics were comparable between the 2 groups. The primary end point of favorable outcome (modified Rankin Scale 0 to 2) at 90 days was somewhat more frequent in the UK group than in the control group (49.1% and 38.6%, OR: 1.54, 95% CI: 0.73 to 3.23) but did not reach a significant level (P=0.345). However, excellent functional outcome (modified Rankin Scale 0 to 1) at 90 days, a preplanned secondary end point, was more frequent in the UK group than in the control group (42.1% and 22.8%, P=0.045, OR: 2.46, 95% CI: 1.09 to 5.54). There were significantly more patients with National Institutes of Health Stroke Scale 0 or 1 at 90 days in the UK group than the control group (P=0.017). The 90-day cumulative mortality was 5.3% in the UK group and 3.5% in the control group (P=1.000), and intracerebral hemorrhage within 24 hours of treatment occurred in 9% and 2%, respectively (P=0.206).\n The trial was aborted prematurely and the primary end point did not reach statistical significance. Nevertheless, the secondary analyses suggested that intraarterial fibrinolysis has the potential to increase the likelihood of excellent functional outcome." ]

[ "12965981", "8395916", "15778874", "17589370", "17296917", "7730690" ]

[ "Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial.", "Effect of dronabinol on nutritional status in HIV infection.", "Dronabinol and marijuana in HIV(+) marijuana smokers: acute effects on caloric intake and mood.", "Dronabinol and marijuana in HIV-positive marijuana smokers. Caloric intake, mood, and sleep.", "Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial.", "Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS." ]

[ "Cannabinoid use could potentially alter HIV RNA levels by two mechanisms: immune modulation or cannabinoid-protease inhibitor interactions (because both share cytochrome P-450 metabolic pathways).\n To determine the short-term effects of smoked marijuana on the viral load in HIV-infected patients.\n Randomized, placebo-controlled, 21-day intervention trial.\n The inpatient General Clinical Research Center at the San Francisco General Hospital, San Francisco, California.\n 67 patients with HIV-1 infection.\n Participants were randomly assigned to a 3.95%-tetrahydrocannabinol marijuana cigarette, a 2.5-mg dronabinol (delta-9-tetrahydrocannabinol) capsule, or a placebo capsule three times daily before meals.\n HIV RNA levels, CD4+ and CD8+ cell subsets, and pharmacokinetic analyses of the protease inhibitors.\n 62 study participants were eligible for the primary end point (marijuana group, 20 patients; dronabinol group, 22 patients; and placebo group, 20 patients). Baseline HIV RNA level was less than 50 copies/mL for 36 participants (58%), and the median CD4+ cell count was 340 x 109 cells/L. When adjusted for baseline variables, the estimated average effect versus placebo on change in log10 viral load from baseline to day 21 was -0.07 (95% CI, -0.30 to 0.13) for marijuana and -0.04 (CI, -0.20 to 0.14) for dronabinol. The adjusted average changes in viral load in marijuana and dronabinol relative to placebo were -15% (CI, -50% to 34%) and -8% (CI, -37% to 37%), respectively. Neither CD4+ nor CD8+ cell counts appeared to be adversely affected by the cannabinoids.\n Smoked and oral cannabinoids did not seem to be unsafe in people with HIV infection with respect to HIV RNA levels, CD4+ and CD8+ cell counts, or protease inhibitor levels over a 21-day treatment.", "To examine the effect of dronabinol (delta-9-tetrahydrocannabinol) on appetite and nutritional status in patients with symptomatic HIV infection and weight loss.\n Double-blind, randomized, placebo-controlled, crossover trial with two five-week treatment periods separated by a two-week washout period. Patients received dronabinol 5 mg twice daily before meals or placebo.\n A university-based HIV/AIDS clinic and a large infectious disease private practice largely devoted to care of patients with HIV.\n Twelve HIV-infected patients who had had at least a 2.25-kg weight loss participated in the study. Five patients completed the protocol, and seven withdrew (two because of drug intolerance, two because of disease progression, two because of noncompliance, and one because of experimental antiretroviral therapy).\n Main outcome measures included caloric intake, weight, percent body fat, serum prealbumin, and symptom distress.\n During dronabinol treatment, subjects experienced increased percent body fat (one percent, p = 0.04); decreased symptom distress (p = 0.04); and trends toward weight gain (0.5 kg, p = 0.13), increased prealbumin (29.0 mg/L, p = 0.11), and improved appetite score (p = 0.14).\n In a selected group of HIV-infected patients with weight loss, short-term treatment with dronabinol may result in improvement in nutritional status and symptom distress.", "No studies to date have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol in HIV(+) marijuana smokers.\n The aim of this study was to compare dronabinol (0, 10, 20, 30 mg p.o.) and marijuana [0.0, 1.8, 2.8, 3.9% Delta(9)-tetrahydrocannabinol (THC)] in two samples of HIV(+) marijuana smokers: those with (n=15) and those without (n=15) a clinically significant loss of muscle mass (<90% body cell mass/height), which is one component of AIDS wasting.\n Mood, physical symptoms, self-selected food intake, cardiovascular data, and cognitive task performance were measured before and repeatedly after dronabinol and marijuana administration in eight 7-h sessions. Marijuana and dronabinol were administered in randomized order using a within-subject, staggered, double-dummy design.\n As compared to placebo, (1) marijuana (1.8, 2.8, 3.9% THC) and the lower dronabinol doses (10, 20 mg) were well tolerated (e.g., few physical symptoms, significant increases in ratings of \"good drug effect\") in both groups of participants; the highest dose of dronabinol (30 mg) was poorly tolerated in a subset of participants; (2) marijuana and dronabinol significantly increased caloric intake in the low bioelectrical impedance analysis (BIA) group but not in the normal BIA group; and (3) drug effects on cognitive performance were minor.\n These data suggest that for experienced marijuana smokers with clinically significant muscle mass loss, both dronabinol (at acute doses at least four to eight times the current recommendation) and marijuana produce substantial and comparable increases in food intake without producing adverse effects.", "Individuals with HIV constitute the largest group using cannabinoids for medicinal reasons; yet, no studies have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol maintenance in HIV-positive marijuana smokers. This placebo-controlled within-subjects study evaluated marijuana and dronabinol across a range of behaviors: eating topography, mood, cognitive performance, physiologic measures, and sleep.\n HIV-positive marijuana smokers (n = 10) completed 2 16-day inpatient phases. Each dronabinol (5 and 10 mg) and marijuana (2.0% and 3.9% Delta9-tetrahydrocannabinol [THC]) dose was administered 4 times daily for 4 days, but only 1 drug was active per day, thereby maintaining double-blind dosing. Four days of placebo washout separated each active cannabinoid condition.\n As compared with placebo, marijuana and dronabinol dose dependently increased daily caloric intake and body weight in HIV-positive marijuana smokers. All cannabinoid conditions produced significant intoxication, except for low-dose dronabinol (5 mg); the intoxication was rated positively (eg, \"good drug effect\") with little evidence of discomfort and no impairment of cognitive performance. Effects of marijuana and dronabinol were comparable, except that only marijuana (3.9% THC) improved ratings of sleep.\n These data suggest that for HIV-positive marijuana smokers, both dronabinol (at doses 8 times current recommendations) and marijuana were well tolerated and produced substantial and comparable increases in food intake.", "To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model.\n Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy. Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days. Primary outcome measures included ratings of chronic pain and the percentage achieving >30% reduction in pain intensity. Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model.\n Fifty patients completed the entire trial. Smoked cannabis reduced daily pain by 34% (median reduction; IQR = -71, -16) vs 17% (IQR = -29, 8) with placebo (p = 0.03). Greater than 30% reduction in pain was reported by 52% in the cannabis group and by 24% in the placebo group (p = 0.04). The first cannabis cigarette reduced chronic pain by a median of 72% vs 15% with placebo (p < 0.001). Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli (p < or = 0.05) but appeared to have little effect on the painfulness of noxious heat stimulation. No serious adverse events were reported.\n Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.", "The effects of dronabinol on appetite and weight were evaluated in 139 patients with AIDS-related anorexia and > or = 2.3 kg weight loss in a multi-institutional study. Patients were randomized to receive 2.5 mg dronabinol twice daily or placebo. Patients rated appetite, mood, and nausea by using a 100-mm visual analogue scale 3 days weekly. Efficacy was evaluable in 88 patients. Dronabinol was associated with increased appetite above baseline (38% vs 8% for placebo, P = 0.015), improvement in mood (10% vs -2%, P = 0.06), and decreased nausea (20% vs 7%; P = 0.05). Weight was stable in dronabinol patients, while placebo recipients had a mean loss of 0.4 kg (P = 0.14). Of the dronabinol patients, 22% gained > or = 2 kg, compared with 10.5% of placebo recipients (P = 0.11). Side effects were mostly mild to moderate in severity (euphoria, dizziness, thinking abnormalities); there was no difference in discontinued therapy between dronabinol (8.3%) and placebo (4.5%) recipients. Dronabinol was found to be safe and effective for anorexia associated with weight loss in patients with AIDS." ]

[ "4617772", "10515648" ]

[ "Preliminary clinical study of acupuncture in rheumatoid arthritis.", "The effect of acupuncture on patients with rheumatoid arthritis: a randomized, placebo-controlled cross-over study." ]

[ "nan", "Acupuncture is commonly used by patients with chronic painful musculoskeletal disorders. There are, however, few well-designed studies of its efficacy. This paper describes a randomized placebo-controlled cross-over design to evaluate acupuncture as a useful treatment adjunct in the management of patients with rheumatoid arthritis (RA).\n Sixty-four patients were centrally randomized from a hospital-based rheumatology out-patient clinic. Fifty-six patients were suitable for study, all were on second-line therapy and aged 18-75 yr. There had been no change in therapy for the preceding 3 months. Patients who had previous acupuncture, anticoagulation, fear of needles or infection were excluded. Single-point (Liver 3) acupuncture or placebo was given with an intervening 6 week wash-out period. The acupuncturist, patient and statistician were blinded as far as possible. The outcome measures included the inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), visual analogue scale of pain, global patient assessment, 28 swollen and tender joint count, and a general health questionnaire.\n The results demonstrated no significant effect of treatment or period and no significant interaction between treatment and period for any outcome variable. No adverse effects were reported.\n Acupuncture of this type cannot be considered as a useful adjunct to therapy in patients with RA. Possible reasons why this is the case are discussed." ]

[ "18196610", "18842978", "16916871" ]

[ "Comparison of an SMS text messaging and phone reminder to improve attendance at a health promotion center: a randomized controlled trial.", "Texting appointment reminders to repeated non-attenders in primary care: randomised controlled study.", "The use of text messaging to improve attendance in primary care: a randomized controlled trial." ]

[ "To compare the efficacy of a short messaging service (SMS) text messaging and phone reminder to improve attendance rates at a health promotion center.\n A total of 1 859 participants who had scheduled appointments in the health promotion center of our hospital from April 2007 to May 2007 were enrolled in the study and randomly assigned into 3 groups: control (no reminder) group, SMS text messaging reminder group and telephone reminder group. Attendance rates and costs of interventions were collected.\n A total of 1848 participants were eligible for analysis. Attendance rates of control, SMS and telephone groups were 80.5%, 87.5% and 88.3%, respectively. The attendance rates were significantly higher in SMS and telephone groups than that in the control group, with odds ratio 1.698, 95% confidence interval 1.224 to 2.316, P=0.001 in the SMS group, and odds ratio 1.829, 95% confidence interval 1.333 to 2.509, P<0.001 in the telephone group. However, there was no difference between the SMS group and the telephone group (P=0.670). The cost effectiveness analysis showed that the cost per attendance for the SMS group (0.31 Yuan) was significantly lower than that for the telephone group (0.48 Yuan).\n SMS and telephone are effective reminders for improving attendance rate at a health promotion center. SMS reminder may be more cost-effective compared with the telephone reminder.", "Failure to attend appointments compromises health service efficiency. Despite considerable interest in using novel technologies to improve attendance, evidence from rigorously conducted controlled studies is lacking.\n To evaluate the effectiveness of texting appointment reminders to patients who persistently fail to attend appointments.\n Randomised controlled study.\n Inner city general practice in Lothian, Scotland.\n We included 415 appointments made by patients (n = 173) who had failed to attend two or more routine appointments in the preceding year. Patients whose appointments were randomised to the intervention group received a text message reminder of the appointment. Patients whose appointments were in the control group received no reminder. Our primary outcome measure was non-attendance rates. We undertook an intention-to-treat analysis and multi-level analysis to take account of the lack of independence of the outcomes of repeated appointments for the same patient.\n Of the 418 appointments originally included in the study, three were excluded due to clerical error; 189 were randomised to the intervention group and 226 to the control group. Twenty-two appointments (12%) were not attended in the intervention group compared with 39 (17%) in the control group. A chi-square analysis, considering the outcome of appointments as independent from one another, gave a non-significant difference of 5% (95% CI of difference -1.1 to 12.3%, p = 0.13). Multilevel analysis applied to the binary outcome data on non-attendance gave an odds ratio for non-attendance in the intervention group compared with the control group of 0.63 (95% CI 0.36 to 1.1, p = 0.11).\n Although the intervention showed promise, we failed to demonstrate significant reduction in non-attendance rates, as a result of texting appointment reminders to patients who persistently fail to attend their general practice appointments.", "Non-attendance is common in primary care and previous studies have reported that reminders were useful in reducing broken appointments.\n To determine the effectiveness of a text messaging reminder in improving attendance in primary care.\n Multicentre three-arm randomized controlled trial.\n Seven primary care clinics in Malaysia. Participants. Patients (or their caregivers) who required follow-up at the clinics between 48 hours and 3 months from the recruitment date. Interventions. Two intervention arms consisted of text messaging and mobile phone reminders 24-48 hours prior to scheduled appointments. Control group did not receive any intervention. Outcome measures. Attendance rates and costs of interventions.\n A total of 993 participants were eligible for analysis. Attendance rates of control, text messaging and mobile phone reminder groups were 48.1, 59.0 and 59.6%, respectively. The attendance rate of the text messaging reminder group was significantly higher compared with that of the control group (odds ratio 1.59, 95% confidence interval 1.17 to 2.17, P = 0.005). There was no statistically significant difference in attendance rates between text messaging and mobile phone reminder groups. The cost of text messaging reminder (RM 0.45 per attendance) was lower than mobile phone reminder (RM 0.82 per attendance).\n Text messaging reminder system was effective in improving attendance rate in primary care. It was more cost-effective compared with the mobile phone reminder." ]

[ "16398774", "11339909", "12969574", "7491136", "9422018", "8059811", "18001442", "7503196", "12660054", "12636956", "19951217", "16709205", "15294856", "10684911", "11519502", "10428520", "1992412", "12040953" ]

[ "A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study.", "Vaginal clindamycin in preventing preterm birth and peripartal infections in asymptomatic women with bacterial vaginosis: a randomized, controlled trial.", "Treatment of asymptomatic bacterial vaginosis to prevent pre-term delivery: a randomised trial.", "Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis.", "Impact of metronidazole therapy on preterm birth in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomised, placebo controlled trial.", "Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study.", "Treatment options for bacterial vaginosis in patients at high risk of preterm labor and premature rupture of membranes.", "Intravaginal clindamycin treatment for bacterial vaginosis: effects on preterm delivery and low birth weight.", "Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised controlled trial.", "Intravaginal clindamycin to reduce preterm birth in women with abnormal genital tract flora.", "Changes in the vaginal microenvironment with metronidazole treatment for bacterial vaginosis in early pregnancy.", "Late miscarriage and preterm birth after treatment with clindamycin: a randomised consent design study according to Zelen.", "Prospective randomised controlled trial of an infection screening programme to reduce the rate of preterm delivery.", "Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.", "Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection.", "Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double-blind trial.", "Amoxicillin treatment of bacterial vaginosis during pregnancy.", "Preterm labour--is bacterial vaginosis involved?" ]

[ "To determine whether metronidazole reduces early preterm labour in asymptomatic women with positive vaginal fetal fibronectin (fFN) in the second trimester of pregnancy.\n Randomised placebo-controlled trial.\n Fourteen UK hospitals (three teaching).\n Pregnancies with at least one previous risk factor, including mid-trimester loss or preterm delivery, uterine abnormality, cervical surgery or cerclage.\n Nine hundred pregnancies were screened for fFN at 24 and 27 weeks of gestation. Positive cases were randomised to a week's course of oral metronidazole or placebo.\n Primary outcome was delivery before 30 weeks of gestation. Secondary outcomes included delivery before 37 weeks.\n The Trial Steering Committee (TSC) recommended the study be stopped early; 21% of women receiving metronidazole (11/53) delivered before 30 weeks compared with 11% (5/46) taking placebo [risk ratio 1.9, 95% confidence interval (CI) 0.72-5.09, P = 0.18]. There were significantly more preterm deliveries (before 37 weeks) in women treated with metronidazole 33/53 (62%) versus placebo 18/46 (39%), risk ratio 1.6, 95% CI 1.05-2.4. fFN was a good predictor of early preterm birth in these asymptomatic women; positive and negative predictive values (24 weeks of gestation) for delivery by 30 weeks were 26% and 99%, respectively (positive and negative likelihood ratios 15, 0.35).\n Metronidazole does not reduce early preterm birth in high risk pregnant women selected by history and a positive vaginal fFN test. Preterm delivery may be increased by metronidazole therapy.", "To determine whether treatment of bacterial vaginosis (BV) in early pregnancy decreases the risk of preterm delivery and peripartum infectious morbidity.\n In this multicenter, randomized, double-masked, placebo-controlled intervention trial, screening for BV was performed by vaginal Gram stain obtained from 5432 healthy women with singleton pregnancies during the first antenatal clinic visit at 10--17 weeks' gestation. Bacterial vaginosis-positive women with no past history of preterm delivery were randomized to a single course of treatment with either 2% vaginal clindamycin cream or identical placebo cream for 7 days. Repeat Gram stains were taken 1 week after treatment and at 30--36 weeks' gestation. Preterm delivery was defined as spontaneous delivery before 37 gestational weeks. Peripartum infectious morbidity was defined as postpartum endometritis, postpartum sepsis, postcesarean wound infection, or episiotomy wound infection, necessitating antimicrobial therapy. According to the power analysis, 180 patients were needed for both treatment arms to show a three-fold difference in the rates of preterm births.\n The overall prevalence of BV was 10.4%. Of all BV-positive women, 375 (66%) were randomized to the treatment arms. The primary cure rate was 66% in the clindamycin group; in the placebo group, 34% spontaneously cleared BV (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.3, 2.8). The rate of preterm deliveries was 5% in the clindamycin group and 4% in the placebo group (OR 1.3, 95% CI 0.5, 3.5). The rate of peripartum infectious morbidity was 11% in the clindamycin group and 18% in the placebo group (OR 1.6, 95% CI 0.9, 2.8). Bacterial vaginosis recurred in 7% of women. The rate of preterm deliveries was 15% in this subgroup compared with 2% among women who remained BV negative (OR 9.3, 95% CI 1.6, 53.5).\n Vaginal clindamycin did not decrease the rate of preterm deliveries or peripartum infections, but recurrent or persistent BV increased the risk for these complications.", "To evaluate the efficacy of clindamycin vaginal cream 2% once daily for 7 days in prolonging pregnancy.\n Randomised clinical trial of 112 women between 14 and 25 weeks of gestation with diagnosis of asymptomatic bacterial vaginosis were enrolled in a multicenter randomised trial and assigned to active or no treatment. A total of 55 women were assigned to clindamycin and 57 to no treatment.\n frequency of pre-term delivery.\n The rates of pre-term delivery was 12.2% in the clindamycin group and 15.7% in the no treatment group (P=0.78). Birth weight was <2500 g in three and seven babies, respectively, in the two groups (P=0.32). Mean gestational ages at birth were 38.9 and 39.2 (P=0.52), respectively, in the clindamycin and no treatment groups.\n The results of this study suggest that treating asymptomatic bacterial vaginosis does neither markedly prolong pregnancy nor increase birthweight.", "Pregnant women with bacterial vaginosis may be at increased risk for preterm delivery. We investigated whether treatment with metronidazole and erythromycin during the second trimester would lower the incidence of delivery before 37 weeks' gestation.\n In 624 pregnant women at risk for delivering prematurely, vaginal and cervical cultures and other laboratory tests for bacterial vaginosis were performed at a mean of 22.9 weeks' gestation. We then performed a 2:1 double-blind randomization to treatment with metronidazole and erythromycin (433 women) or placebo (191 women). After treatment, the vaginal and cervical tests were repeated and a second course of treatment was given to women who had bacterial vaginosis at that time (a mean of 27.6 weeks' gestation).\n A total of 178 women (29 percent) delivered infants at less than 37 weeks' gestation. Eight women were lost to follow-up. In the remaining population, 110 of the 426 women assigned to metronidazole and erythromycin (26 percent) delivered prematurely, as compared with 68 of the 190 assigned to placebo (36 percent, P = 0.01). However, the association between the study treatment and lower rates of prematurity was observed only among the 258 women who had bacterial vaginosis (rate of preterm delivery, 31 percent with treatment vs. 49 percent with placebo; P = 0.006). Of the 358 women who did not have bacterial vaginosis when initially examined, 22 percent of those assigned to metronidazole and erythromycin and 25 percent of those assigned to placebo delivered prematurely (P = 0.55). The lower rate of preterm delivery among the women with bacterial vaginosis who were assigned to the study treatment was observed both in women at risk because of previous preterm delivery (preterm delivery in the treatment group, 39 percent; and in the placebo group, 57 percent; P = 0.02) and in women who weighed less than 50 kg before pregnancy (preterm delivery in the treatment group, 14 percent; and in the placebo group, 33 percent; P = 0.04).\n Treatment with metronidazole and erythromycin reduced rates of premature delivery in women with bacterial vaginosis and an increased risk for preterm delivery.", "To ascertain whether metronidazole treatment of women with a heavy growth of Gardnerella vaginalis during mid-pregnancy would reduce the risk of spontaneous preterm birth.\n A multicentre, randomised, placebo-controlled trial.\n Four metropolitan hospitals.\n Eight hundred and seventy-nine singleton women with a heavy growth of G. vaginalis or Gram stain indicative of bacterial vaginosis at 19 weeks of gestation.\n Oral metronidazole (400 mg) or placebo twice daily for two days at 24 weeks of gestation, and at 29 weeks if G. vaginalis found in test-of-cure swab four weeks after treatment.\n Spontaneous preterm birth less than 37 weeks.\n Intention-to-treat analysis showed no difference between metronidazole and placebo groups in overall preterm birth (31/429 [7.2%] vs 32/428 [7.5%]) or spontaneous preterm birth (20/429 [4.7%] vs 24/428 [5.6%]). Among the 480 women with bacterial vaginosis treatment had no effect on spontaneous preterm birth (11/242 [4.5%] vs 15/238 [6.3%]). In the subset of 46 women with a previous preterm birth, women in the metronidazole group showed a significant reduction in spontaneous preterm birth (2/22 [9.1%] vs 10/24 [41.7%], OR 0.14, 95% CI 0.01-0.84). A treatment effect was also found in compliant women with a previous preterm birth and bacterial vaginosis (0/14 [0%] vs 6/17 [35.3%], OR 0.0, 95% CI 0.0-0.94).\n Metronidazole treatment of women with a heavy growth of G. vaginalis or bacterial vaginosis did not reduce the preterm birth rate. Among women with a previous preterm birth, treatment reduced the risk of spontaneous preterm birth. Further studies are required to confirm these findings.", "Our purpose was to determine whether treatment of bacterial vaginosis with metronidazole in patients with preterm delivery in the penultimate pregnancy from preterm labor or premature rupture of membranes reduces the risk of subsequent preterm birth.\n From January 1989 to June 1992 patients with a singleton gestation between 13 and 20 weeks and a history of preterm birth in the preceding pregnancy from either idiopathic preterm labor or premature rupture of membranes were screened for bacterial vaginosis. Those with a positive screen were randomized to receive 250 mg of metronidazole three times a day for 7 days or placebo in a double-blind design. Data were analyzed with Student t and chi 2 tests, and differences considered significant at p < 0.05.\n Of 94 eligible patients, 80 were enrolled and completed the study, of which 44 received metronidazole. Both groups were comparable in number of entry variables. Compared with the placebo group, patients in the metronidazole group had significantly fewer hospital admissions for preterm labor, 12 (27%) versus 28 (78%); preterm births, eight (18%) versus 16 (39%); births of infants weighing < 2500 gm, six (14%) versus 12 (33%); and premature rupture of membranes, two (5%) versus 12 (33%).\n Treatment of bacterial vaginosis with metronidazole was effective in reducing preterm births in patients with a history of prematurity in the preceding pregnancy.", "To estimate the efficacy of different therapeutic modalities on proven cases of bacterial vaginosis (BV) in patients at high risk of preterm labor and premature rupture of membranes.\n This was a longitudinal prospective comparative study set in the antenatal outpatient clinic of the department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University, Assiut, Egypt. Four hundred and sixty-eight patients with a clinical picture of threatened preterm labor or at high risk of premature rupture of membranes in the third trimester were screened for BV. Positive BV was diagnosed in 156 patients. They were randomly classified into four equal groups according to the line of medical treatment. The treatments were: (i) oral metronidazole, (ii) clindamycin vaginal cream, (iii) oral clindamycin, or (iv) metronidazole vaginal suppositories. The effects of medical treatment on Amsel's criteria as well as maternal and fetal outcomes were measured.\n Based on Amsel's criteria, 156 patients (33.3%) were diagnosed with BV. There was a significant disappearance of vaginal discharge, with decreased percentages of pH > 4.5, positive amine test, and clue cells after treatment of BV in the four groups without any statistically significant difference between them. There were variable effects of the different treatments on increasing birthweight values, admission to neonatal intensive care units, and prolongation of the gestational age. Some maternal adverse effects have been recorded. There were significant improvements of the outcomes for oral metronidazole and clindamycin compared with outcomes for intravaginal metronidazole and clindamycin.\n Metronidazole and clindamycin achieve nearly equivalent cure rates when administered orally or vaginally in patients at high risk of preterm labor and premature rupture of membranes. Oral metronidazole is considered the drug of choice in treating BV due its high cure rate, better outcomes, and low cost.", "Our goal was to evaluate whether treatment of bacterial vaginosis during pregnancy with 2% clindamycin vaginal cream reduces the incidence of either preterm delivery or low birth weight or of both.\n A multicenter, double-blind, randomized, placebo-controlled trial in Indonesia compared a 2% clindamycin vaginal cream with a placebo cream. Women seeking prenatal care at 14 to 26 weeks of gestational age who had bacterial vaginosis (Gram stain score > 6 and pH of vaginal fluid > 4.5) were invited to participate. Of the 745 women enrolled, 681 (91.4%) women were followed up through delivery.\n Clindamycin vaginal cream was an effective treatment for bacterial vaginosis. Two weeks after completion of the treatment, 85.5% of the women were cured. The rate of preterm delivery (< 37 weeks) was 15.0% for clindamycin patients and 13.5% for placebo patients (odds ratio 1.1, 95% confidence interval 0.7 to 1.7). The rate of low birth weight was 9.0% for clindamycin patients and 6.8% for placebo patients (odds ratio 1.3, 95% confidence interval 0.8 to 2.4).\n Treatment of bacterial vaginosis with clindamycin vaginal cream did not reduce preterm delivery or low birth weight. Although clindamycin vaginal cream is an effective treatment for bacterial vaginosis, intravaginal treatment would not be effective against bacterial vaginosis-associated microorganisms harbored in the upper genital tract. Systemic treatment may be required to eradicate upper tract infection to reduce preterm delivery.", "Abnormal vaginal flora and bacterial vaginosis are associated with amplified risks of late miscarriage and spontaneous preterm delivery. We aimed to establish whether antibiotic treatment early in the second trimester might reduce these risks in a general obstetric population.\n We screened 6120 pregnant women attending hospital for their first antenatal visit--who were at 12-22 weeks' gestation (mean 15.6 weeks)--for bacterial vaginosis or abnormal vaginal flora. We used gram-stained slides of vaginal smears to diagnose abnormal vaginal flora or bacterial vaginosis, in accordance with Nugent's criteria. We randomly allocated 494 women with one of these signs to receive either clindamycin 300 mg or placebo orally twice daily for 5 days. Primary endpoints were spontaneous preterm delivery (birth > or =24 but <37 weeks) and late miscarriage (pregnancy loss > or =13 but <24 weeks). Analysis was intention to treat.\n Nine women were lost to follow-up or had elective termination. Thus, we analysed 485 women with complete outcome data. Women receiving clindamycin had significantly fewer miscarriages or preterm deliveries (13/244) than did those in the placebo group (38/241; percentage difference 10.4%, 95% CI 5.0-15.8, p=0.0003). Clindamycin also reduced adverse outcomes across the range of abnormal Nugent scores, with maximum effect in women with the highest Nugent score of 10.\n Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the second trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth in a general obstetric population.", "To assess the ability of clindamycin vaginal cream to reduce the incidence of preterm birth in women with abnormal genital tract flora in the second trimester of pregnancy.\n This was a randomized, double-blind, placebo-controlled, tricenter study. A total of 409 women with abnormal genital tract flora on Gram stain of vaginal secretions at 13-20 weeks' gestation were randomized to receive a 3-day course of clindamycin vaginal cream or placebo. Those women who still had abnormal vaginal flora 3 weeks later received a 7-day course of the original study drug (ie, either clindamycin vaginal cream or placebo as per original randomization). The primary outcome measure was the incidence of preterm birth.\n There was a statistically significant reduction in the incidence of preterm birth in the clindamycin vaginal cream group (4%) compared with placebo (10%) (P <.03). Significantly more babies born preterm (63%) required admission to the neonatal intensive care unit compared with term infants (4%) (P <.001).\n A 2% clindamycin vaginal cream, when compared with placebo administered to women with abnormal genital tract flora before 20 weeks' gestation, can reduce the incidence of preterm birth by 60% and hence the need for neonatal intensive care.", "Bacterial vaginosis (BV) is associated with preterm delivery, but there is little evidence that treatment improves pregnancy outcomes. We examined whether oral or vaginal metronidazole treatment for BV in early pregnancy was more effective in restoring the normal vaginal environment.\n This was a randomized controlled trial comparing oral and intravaginal metronidazole for treatment of BV in early pregnancy (<20 weeks). Vaginal samples collected at baseline and 4 weeks after treatment were evaluated using gram stain, culture, colorimetric detection of sialidase, and immunoassay for measurement of proinflammatory cytokines interleukins-1beta, -6, -8 (IL-1beta, IL-6, IL-8) and secretory leukocyte protease inhibitor (SLPI). We compared the effect of treatment between groups (using chi-square and t test) and within individuals (McNemar's test).\n Of 126 subjects, 108 (86%) completed follow-up (55 oral, 53 intravaginal). Of the study population, 34% achieved therapeutic cure, and this was not different between treatment groups. BV-associated bacteria were significantly reduced in both groups, but few subjects regained colonization with protective lactobacilli. Among women who achieved therapeutic cure, the level of IL-1beta dropped significantly (p < 0.001) and SLPI increased (p = 0.003). More women in the vaginal treatment group had undetectable sialidase after treatment (p = 0.013).\n Treatment with oral or intravaginal metronidazole in early pregnancy reduced colonization with BV-associated bacteria but was not effective in achieving therapeutic cure or in restoring healthy vaginal lactobacilli.", "To screen for bacterial vaginosis (BV) and to investigate the effect of treatment with vaginal clindamycin in order to observe the effect on late miscarriage and delivery prior to 37 completed weeks (primary outcome).\n Randomised consent design for clinical trials according to Zelen.\n Southeast region of Sweden.\n A total of 9025 women were screened in early pregnancy.\n A total of 819 women with a Nugent score of 6 and above were considered to have BV and treated according to Zelen allocation. The incidence of late miscarriage and spontaneous (noniatrogenic) preterm birth was assessed.\n Late miscarriage and spontaneous preterm delivery before 37 weeks.\n Therapy with vaginal clindamycin had no significant impact on the incidence of spontaneous preterm delivery prior to 37 completed weeks; OR 0.90, 95% CI 0.40-2.02 (primary outcome variable). However, only 1 of 11 women in the treatment group versus 5 of 12 in the control group delivered prior to 33 completed weeks; OR 0.14, 95% CI 0.02-0.95. Treatment was associated with 32 days longer gestation for the 23 participants who had late miscarriage or spontaneous preterm birth (P= 0.024, Mann-Whitney U test) and significantly fewer infants had a birthweight below 2,500 g (secondary outcome). A follow up of infants born preterm 4 years postnatally indicated that extending gestational age did not increase the number of sequelae.\n Clindamycin vaginal cream therapy was associated with significantly prolonged gestation and reduced cost of neonatal care in women with BV. Early screening for BV and treatment with clindamycin saved approximately 27 euro per woman.", "To evaluate whether a screening strategy in pregnancy lowers the rate of preterm delivery in a general population of pregnant women.\n Multicentre, prospective, randomised controlled trial.\n Non-hospital based antenatal clinics.\n 4429 pregnant women presenting for their routine prenatal visits early in the second trimester were screened by Gram stain for asymptomatic vaginal infection. In the intervention group, the women's obstetricians received the test results and women received standard treatment and follow up for any detected infection. In the control group, the results of the vaginal smears were not revealed to the caregivers.\n The primary outcome variable was preterm delivery at less than 37 weeks. Secondary outcome variables were preterm delivery at less than 37 weeks combined with different birth weight categories equal to or below 2500 g and the rate of late miscarriage.\n Outcome data were available for 2058 women in the intervention group and 2097 women in the control group. In the intervention group, the number of preterm births was significantly lower than in the control group (3.0% v 5.3%, 95% confidence interval 1.2 to 3.6; P = 0.0001). Preterm births were also significantly reduced in lower weight categories at less than 37 weeks and <or= 2500 g. Eight late miscarriages occurred in the intervention group and 15 in the control group.\n Integrating a simple infection screening programme into routine antenatal care leads to a significant reduction in preterm births and reduces the rate of late miscarriage in a general population of pregnant women.", "Bacterial vaginosis has been associated with preterm birth. In clinical trials, the treatment of bacterial vaginosis in pregnant women who previously had a preterm delivery reduced the risk of recurrence.\n To determine whether treating women in a general obstetrical population who have asymptomatic bacterial vaginosis (as diagnosed on the basis of vaginal Gram's staining and pH) prevents preterm delivery, we randomly assigned 1953 women who were 16 to less than 24 weeks pregnant to receive two 2-g doses of metronidazole or placebo. The diagnostic studies were repeated and a second treatment was administered to all the women at 24 to less than 30 weeks' gestation. The primary outcome was the rate of delivery before 37 weeks' gestation.\n Bacterial vaginosis resolved in 657 of 845 women who had follow-up Gram's staining in the metronidazole group (77.8 percent) and 321 of 859 women in the placebo group (37.4 percent). Data on the time and characteristics of delivery were available for 953 women in the metronidazole group and 966 in the placebo group. Preterm delivery occurred in 116 women in the metronidazole group (12.2 percent) and 121 women in the placebo group (12.5 percent) (relative risk, 1.0; 95 percent confidence interval, 0.8 to 1.2). Treatment did not prevent preterm deliveries that resulted from spontaneous labor (5.1 percent in the metronidazole group vs. 5.7 percent in the placebo group) or spontaneous rupture of the membranes (4.2 percent vs. 3.7 percent), nor did it prevent delivery before 32 weeks (2.3 percent vs. 2.7 percent). Treatment with metronidazole did not reduce the occurrence of preterm labor, intraamniotic or postpartum infections, neonatal sepsis, or admission of the infant to the neonatal intensive care unit.\n The treatment of asymptomatic bacterial vaginosis in pregnant women does not reduce the occurrence of preterm delivery or other adverse perinatal outcomes.", "Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery. It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery.\n We screened pregnant women for trichomoniasis by culture of vaginal secretions. We randomly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation. The primary outcome was delivery before 37 weeks of gestation.\n Between randomization and follow-up, trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group (92.6 percent) and 92 of 260 women with follow-up cultures in the placebo group (35.4 percent). Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group. Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group (19.0 percent) and 31 women in the placebo group (10.7 percent) (relative risk, 1.8; 95 percent confidence interval, 1.2 to 2.7; P=0.004). The difference was attributable primarily to an increase in preterm delivery resulting from spontaneous preterm labor (10.2 percent vs. 3.5 percent; relative risk, 3.0; 95 percent confidence interval, 1.5 to 5.9).\n Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery. Routine screening and treatment of asymptomatic pregnant women for this condition cannot be recommended.", "To test the hypothesis that prophylactic administration of clindamycin 2% vaginal cream can reduce the incidence of preterm birth in a high risk population.\n A multi-centre, randomised, double-blind, placebo-controlled trial.\n Twelve city hospitals in The Netherlands.\n One hundred and sixty-eight women with a singleton pregnancy and a history of a spontaneous preterm delivery in the preceding pregnancy.\n Clindamycin 2% vaginal cream, or placebo cream, administered daily for seven days at 26 and 32 weeks of gestation.\n Spontaneous preterm birth at < 37 weeks, admission for threatened preterm labour, neonatal infectious morbidity.\n In the intention-to-treat analysis no difference was found in overall preterm birth between clindamycin and placebo (23% vs 18%, respectively). In the subgroup who completed the trial and administered all medication, more women delivered before 34 weeks in the clindamycin group (1.4% in the placebo vs 9.0% in the clindamycin group; P < 0.05). The length of admissions for threatened preterm labour did not differ. More infectious neonatal morbidity was seen in the clindamycin group (5/83 vs 0/85; P < 0.05).\n Clindamycin 2% vaginal cream given prophylactically to women with a spontaneous preterm birth in the preceding pregnancy did not prevent preterm delivery or reduce the number of admissions for threatened preterm labour. The neonatal infectious morbidity in the group treated with clindamycin was significantly higher and a major concern.", "The purpose of this investigation was to evaluate the efficacy of amoxicillin for treatment of bacterial vaginosis during pregnancy. The diagnosis of bacterial vaginosis was established by clinical examination and microscopic examination of a Gram stain and saline preparation of vaginal secretions. In a double-blind, randomized manner, 108 patients at 15-25 weeks' gestation were assigned to treatment with oral amoxicillin, 500 mg three times daily for 14 days, or placebo. Patients were evaluated 2 weeks after treatment, at 34-36 weeks' gestation, and at delivery. There were no significant differences between the two groups with respect to any clinical or microbiologic measure of treatment outcome. There were also no significant differences in the frequency of obstetric complications. We conclude that amoxicillin is not effective therapy for bacterial vaginosis in pregnant women.", "To assess the efficacy of treatment of bacterial vaginosis (BV) using metronidazole to reduce preterm labour in primigravidae and multigravidae with previous midtrimester abortion or preterm labour.\n Randomised controlled trial.\n Tertiary academic hospital.\n Two different groups of patients were screened for BV at the first antenatal visit, namely primigravidae and high-risk multigravidae who had had a previous midtrimester abortion or preterm delivery. Patients where BV was diagnosed clinically or on Gram's stain of a smear taken from the posterior vaginal fornix, received either 400 mg metronidazole, or 100 mg vitamin C orally twice daily for 2 days. The Gram's stain was repeated after 4 weeks. If BV was found again, treatment with the same drug was repeated.\n Preterm delivery, birth weight and perinatal deaths.\n One thousand and five patients entered the study, but 40 were excluded for various reasons and 10 were lost to follow-up. There were 464 primigravidae, of whom 150 (32%) had BV. Except for the 5-minute Apgar score, no significant differences were found between primigravidae negative for BV and those who received either metronidazole or vitamin C. There were 491 high-risk multigravidae, of whom 127 (26%) had BV. The mean gestational age in the BV-negative group was 37 weeks, in contrast to 37.4 weeks in the vitamin C group and 35.6 weeks in the metronidazole group. Birth weights in these three groups were 2,752 g, 2,759 g and 2,475 g respectively, significantly less (P = 0.0109) in the metronidazole group in comparison with the BV-negative group. Delivery before 37 weeks occurred in 29% of high-risk multigravidae with no BV but in 24% of those who took vitamin C and in 43% who took metronidazole. Differences were significant between the BV-negative and metronidazole groups (P = 0.0231) and also between the metronidazole and vitamin C groups (P = 0.0274). Delivery before 28 weeks occurred in 4% of the high-risk multigravidae with no BV but in 10% of those with BV who took metronidazole. The difference was significant (P = 0.0430). Analysis for maximum likelihood estimates for preterm labour identified only previous preterm labour or midtrimester abortion as risk factors.\n Metronidazole does not seem to reduce the prevalence of preterm labour when given for BV before 26 weeks' gestation." ]

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[ "Comparative cocaine abuse treatment strategies: enhancing client retention and treatment exposure.", "A randomized controlled study of the effectiveness of intensive outpatient treatment for cocaine dependence.", "Broad beneficial effects of cocaine abstinence reinforcement among methadone patients.", "Continuity of care and desipramine in primary cocaine abusers.", "Reinforcement-based therapy: 12-month evaluation of an outpatient drug-free treatment for heroin abusers.", "Psychotherapy and pharmacotherapy for ambulatory cocaine abusers.", "Incentives improve outcome in outpatient behavioral treatment of cocaine dependence.", "Neurobehavioral treatment for cocaine-using methadone patients: a preliminary report.", "Motivationally enhanced group counseling for substance users in a soup kitchen: a randomized clinical trial.", "One-year follow-up of disulfiram and psychotherapy for cocaine-alcohol users: sustained effects of treatment.", "A comparison of contingency management and cognitive-behavioral approaches during methadone maintenance treatment for cocaine dependence.", "Randomized controlled trial of brief cognitive-behavioural interventions among regular users of amphetamine.", "Achieving cocaine abstinence with a behavioral approach.", "Effect of prize-based incentives on outcomes in stimulant abusers in outpatient psychosocial treatment programs: a national drug abuse treatment clinical trials network study.", "Prize reinforcement contingency management for cocaine dependence: integration with group therapy in a methadone clinic.", "Sustained cocaine abstinence in methadone maintenance patients through voucher-based reinforcement therapy.", "Schedule of voucher delivery influences initiation of cocaine abstinence.", "Brief coping skills treatment for cocaine abuse: substance use outcomes at three months.", "Superior efficacy of cognitive-behavioral therapy for urban crack cocaine abusers: main and matching effects.", "Group counseling versus individualized relapse prevention aftercare following intensive outpatient treatment for cocaine dependence: initial results.", "Relapse prevention treatment for cocaine dependence: group vs. individual format.", "Psychosocial treatments for cocaine dependence: National Institute on Drug Abuse Collaborative Cocaine Treatment Study.", "A reinforcement-based therapeutic workplace for the treatment of drug abuse: six-month abstinence outcomes.", "Contingent reinforcement increases cocaine abstinence during outpatient treatment and 1 year of follow-up.", "Community reinforcement therapy for cocaine-dependent outpatients." ]

[ "The current investigation explores the clinical utility in providing a series of enhanced clinical services to a sample of 303 cocaine-abusing clients (primarily crack smokers) relative to a standard group therapy treatment program. In addition to examining the comparative impact of six varying psychosocial treatment approaches for cocaine abuse on client retention and treatment exposure rates, an additional emphasis has been to examine the ability of fixed and dynamic client variables in predicting client outcome in this regard. No fixed (e.g., sex, income, marital status, income level, or employment status) or dynamic (e.g., recent alcohol use, antisocial personality disorder diagnoses, or motivational variables) client characteristics were useful in predicting client retention or treatment exposure rates. Program characteristics, however, or the frequency, intensity, and/or type of treatment services offered, were related to client retention and treatment exposure. Treatment exposure and retention were significantly enhanced by providing clients with more frequent and intensive group therapy, or by adding individual treatment services to a standard group therapy treatment regimen. With a population such as cocaine abusers, who typically have an extremely high treatment dropout rate, an obvious strategy is to focus efforts on engaging and retaining clients in treatment, and maximizing levels of treatment exposure. The current findings suggest that one successful approach towards enhancing psychosocial treatments for cocaine abuse is to increase the frequency, intensity, and/or types of treatment services offered.", "A randomized controlled study design was used to compare the effectiveness of intensive outpatient treatment with individual outpatient counseling and a combination of individual and group outpatient counseling for cocaine-dependent patients.\n Volunteers for this study were recruited from among first admissions to an inner-city, public-sector outpatient substance abuse clinic. In-treatment, end-of-treatment, and nine-month follow-up assessments were compared for participants randomly assigned for 12 weeks to one of three treatment modalities--weekly individual outpatient counseling, weekly individual counseling plus one weekly group session, or a newly designed intensive group treatment program consisting of three hours of group treatment three days a week.\n Patients who completed the intensive program showed significant improvement from intake to end-of-treatment scores on the Addiction Severity Index, the Beck Depression Inventory, and the Symptom Checklist. At nine-month follow-up, patients who had remained in treatment longer had fewer drug problems, a smaller proportion of positive urine drug screening tests, a better employment status, and fewer psychological problems compared with patients who left treatment earlier. Patients who remained in treatment were also more likely to be attending self-help meetings, continuing in outpatient treatment, or attending school. However, for the 447 patients randomly assigned to the three conditions, there were no significant differences between treatment modalities on any of the variables at nine-month follow-up. The new intensive treatment program was not shown to be superior to more traditional treatment programs.", "Escalating reinforcement for sustained abstinence has been effective in treating cocaine abuse. Under this schedule, patients receive vouchers for cocaine-free urine samples; vouchers have monetary values that increase with the number of consecutive cocaine-free urine samples. Cocaine-abusing methadone patients were randomly assigned to receive vouchers for 12 weeks under (a) an escalating schedule (n = 20), (b) an escalating schedule with start-up bonuses (n = 20), or (c) a noncontingent schedule (n = 19). Start-up bonuses were designed to provide added reinforcement for initiating abstinence; however, they did not improve outcomes. Both contingent interventions significantly increased cocaine abstinence. In addition, the contingent interventions increased abstinence from opiates and decreased reports of cocaine craving. These results replicate the efficacy of cocaine abstinence reinforcement and show that it can have broad beneficial effects.", "The objective of this research was to determine the efficacy of enhanced continuity of care and desipramine in increasing treatment attendance and abstinence from cocaine in primary cocaine abusers. Study design was a random assignment, placebo-controlled factorial with assessments at baseline and at 3 (first week of outpatient treatment), 8, and 12 weeks after start of study. Desipramine blood levels were taken at weeks 2 (inpatient), 3, and 8. Subjects (N = 94 men) were recruited on an inpatient ward and assigned to increased continuity of care or to standard treatment, and to active or placebo drug. Main outcome variables were toxicology-verified reports of cocaine use, and attendance at counseling sessions. Enhanced continuity of care increased abstinence from cocaine at week 3 and increased attendance at individual counseling sessions throughout the 12 weeks of the study. There were no main effects for desipramine. Blood levels above 123 ng/ml at week 2 predicted longer stays in outpatient. We conclude that enhanced continuity of care is a low cost intervention that improves early treatment outcome and attendance; desipramine effects do not warrant its therapeutic use.", "This controlled study examined the efficacy of reinforcement-based therapy (RBT) for producing enhanced abstinence outcomes over 12 months in opioid-dependent patients exiting a brief residential detoxification. Patients were randomly assigned upon completing their medically managed taper (i.e., detoxification) to RBT (N=66) or usual care (N=64) referral to community treatment programs. The 6-month RBT program offered an array of abstinence-based incentives including rent payment for recovery housing, program-led recreational activities and skills training for procuring employment. RBT produced significantly higher self-report and urinalysis-confirmed rates of abstinence from opioids and cocaine relative to usual care at 1 (42% versus 15%) and 3 (38% versus 17%) months during treatment but not at 6 or 12 months after enrollment. The RBT but not the usual care group showed significant increases in the number of days worked and the amount of legal income earned at 3, 6 and 12 months. The results of this randomized study suggest that an intensive reinforcement-based therapy that includes abstinence-based recovery housing is a promising approach; however, further research is needed to determine the role of treatment intensity and the specific efficacy of RBT's component parts.", "At present, there is no consensus regarding effective treatment for cocaine abuse or the most productive roles for the two major forms of treatment, pharmacotherapy and psychotherapy. We conducted the first randomized clinical trial evaluating psychotherapy and pharmacotherapy, alone and in combination, as treatment for ambulatory cocaine abusers.\n One hundred thirty-nine subjects were assigned to one of four conditions offered over a 12-week abstinence initiation trial: relapse prevention plus desipramine hydrochloride, clinical management plus desipramine, relapse prevention plus placebo, and clinical management plus placebo. All treatments were manual-guided, delivered by experienced therapists, and monitored to promote the integrity of both forms of treatment.\n First, although all groups showed significant improvement, significant main effects for medication or psychotherapy, or their combination, were not found for treatment retention, reduction in cocaine use, or other outcomes at 12 weeks. Second, baseline severity of cocaine use interacted differently with psychotherapy and pharmacotherapy: higher-severity patients had significantly better outcome when treated with relapse prevention than with clinical management, while desipramine was associated with improved abstinence initiation among lower-severity subjects. Third, desipramine was significantly more effective than placebo in reducing cocaine use over 6, but not 12, weeks of treatment. Fourth, depressed subjects had greater reduction in cocaine use than nondepressed subjects and had better response to relapse prevention than to clinical management.\n These findings underscore the significance of heterogeneity among cocaine abusers and the need to develop specialized treatments for clinically distinct subgroups of cocaine abusers.", "To assess whether incentives improved treatment outcome in ambulatory cocaine-dependent patients.\n Forty cocaine-dependent adults were randomly assigned to behavioral treatment with or without an added incentive program. The behavioral treatment was based on the Community Reinforcement Approach and was provided to both groups. Subjects in the group with incentives received vouchers exchangeable for retail items contingent on submitting cocaine-free urine specimens during weeks 1 through 12 of treatment, while the group without incentives received no vouchers during that period. The two groups were treated the same during weeks 13 through 24.\n Seventy-five percent of patients in the group with vouchers completed 24 weeks of treatment vs 40% in the group without vouchers (P = .03). Average durations of continuous cocaine abstinence documented via urinalysis during weeks 1 through 24 of treatment were 11.7 +/- 2.0 weeks in the group with vouchers vs 6.0 +/- 1.5 weeks in the group without vouchers (P = .03). At 24 weeks after treatment entry, the voucher group evidenced significantly greater improvement than the no-voucher group on the Drug scale of the Addiction Severity Index (ASI), and only the voucher group showed significant improvement on the ASI Psychiatric scale.\n Incentives delivered contingent on submitting cocaine-free urine specimens significantly improve treatment outcome in ambulatory cocaine-dependent patients.", "Preliminary outcome evaluation results are reported for an innovative cocaine abuse treatment model adapted for cocaine-using methadone patients. Sixty-two patients were randomly assigned to six months of high intensity (\"neurobehavioral\") or lower intensity (\"control\") therapy for cocaine dependence. Therapy was completed by 49% of neurobehavioral and 53% of control patients. In paired comparisons between intake and six-month follow-up, neurobehavioral patients but not controls showed significant declines in cocaine and other drug use (measured by urinalysis and self-reports), as well as significant improvement in psychological status. The findings suggest that specialized cocaine abuse treatment can benefit methadone patients; intake to the study is continuing.", "Soup kitchens tend to serve residentially unstable adults characterized by a high prevalence of substance abuse. In this study, 289 soup kitchen guests who reported drug or alcohol problems were randomly assigned to information and referral (I&R) plus peer advocacy (peers encouraging subjects to participate in other services) (N = 139) or to an experimental 12-session motivational group (three sessions per week for 4 weeks) followed by a 36-session cognitive-behavioral group (three sessions per week for 12 weeks), plus I&R and peer advocacy. Mean age was 42; 82% male; 68% African-American; 81% unstable residence; 14% HIV+. Experimentals were significantly more likely than the controls to have increased their participation in some type of substance abuse intervention during the follow-up period. In addition, experimentals were significantly more likely than controls to have reduced both drinking and heavy drinking at follow-up (there was no difference between groups in reduction of cocaine use). Interaction analysis indicated that the experimental intervention was more effective for participants with higher rather than lower substance abuse severity at baseline. These results support the concept that motivationally enhanced group counseling, provided as a low-threshold outreach intervention, can help to increase participation in formal treatment and 12-step groups and to reduce substance abuse, particularly for those starting with high severity of use.", "To evaluate outcomes 1 year after cessation of treatment for cocaine- and alcohol-dependent individuals.\n Randomized controlled trial.\n Urban substance abuse treatment center.\n Ninety-six of 122 subjects randomized to treatment.\n One of five treatments delivered over 12 weeks. Cognitive-behavioral treatment (CBT) plus disulfiram; Twelve-Step facilitation (TSF) plus disulfiram; clinical management (CM) plus disulfiram; CBT without disulfiram; TSF without disulfiram.\n Percentage of days of cocaine and alcohol use during follow-up, verified by urine toxicology screens and breathalyzer tests.\n First, as a group, participants reported significant decreases in frequency of cocaine, but not alcohol, use after the end of treatment. Secondly, the main effects of disulfiram on cocaine and alcohol use were sustained during follow-up. Finally, initiation of abstinence for even brief periods of time within treatment was associated with significantly better outcome during follow-up.\n These findings support the efficacy of disulfiram with this challenging population and suggest that comparatively brief treatments that facilitate the initiation of abstinence may have long-term benefits.", "This study compared 2 psychosocial approaches for the treatment of cocaine dependence: contingency management (CM) and cognitive-behavioral therapy (CBT).\n Patients with cocaine dependence who were receiving methadone maintenance treatment (n = 120) were randomly assigned to 1 of 4 conditions: CM, CBT, combined CM and CBT (CBT + CM), or treatment as usual (ie, methadone maintenance treatment program only [MMTP only]) (n = 30 per cell). The CM procedures and CBT materials were comparable to those used in previously published research. The active study period was 16 weeks, requiring 3 clinic visits per week. Participants were evaluated during treatment and at 17, 26, and 52 weeks after admission.\n Urinalysis results during the 16-week treatment period show that participants assigned to the 2 groups featuring CM had significantly superior in-treatment urinalysis results, whereas urinalysis results from participants in the CBT group were not significantly different than those from the MMTP-only group. At week 17, self-reported days of cocaine use were significantly reduced from baseline levels for all 3 treatment groups but not for the MMTP-only group. At the 26-week and 52-week follow-up points, CBT participants showed substantial improvement, resulting in equivalent performance with the CM groups as indicated by both urinalysis and self-reported cocaine use data.\n Study findings provide solid evidence of efficacy for CM and CBT. Although the effect of CM is significantly greater during treatment, CBT appears to produce comparable long-term outcomes. There was no evidence of an additive effect for the 2 treatments in the CM + CBT group.", "To identify whether brief cognitive-behavioural interventions are feasible among regular users of amphetamine, to assess the effectiveness of intervention overall and to pilot two- and four-session interventions.\n Subjects were assigned randomly to individually receive a cognitive-behavioural intervention (n = 32) of either two or four sessions' duration or a self-help booklet (control condition; n = 32).\n Subjects were volunteers recruited from needle exchange schemes and treatment centres in Newcastle, Australia.\n Regular (at least monthly) users of amphetamine were recruited.\n Either four sessions of cognitive-behaviour therapy, consisting of a motivational interview and skills training in avoidance of high-risk situations, coping with craving and relapse prevention, or two sessions consisting of a motivational interview and discussion of skills.\n The Opiate Treatment Index was the main measure at pre-treatment and 6-month follow-up.\n There was a significant reduction in amphetamine use among the sample as a whole, with inconclusive differences between intervention subgroups. There was a moderate overall intervention effect, with the intervention group reporting over twice the reduction in daily amphetamine use as the control group. Significantly more people in the cognitive-behavioural intervention condition abstained from amphetamine at 6-month follow-up compared to the control condition.\n Brief cognitive-behavioural interventions appear feasible among regular users of amphetamine. A larger randomised controlled trial of the effectiveness of such interventions appears warranted.", "The authors compared the efficacy of a multicomponent behavioral treatment and drug abuse counseling for cocaine-dependent individuals.\n The 38 patients were enrolled in outpatient treatment and were randomly assigned to the two treatments. Counseling in the behavioral treatment was based on the community reinforcement approach, while the drug abuse counseling was based on the disease model of dependence and recovery. Patients in the behavioral, but not the drug counseling, treatment also received incentives contingent on submitting cocaine-free urine specimens.\n Of the 19 patients who received behavioral treatment, 58% completed 24 weeks of treatment, versus 11% of the patients who received counseling. In the behavioral treatment group 68% and 42% of the patients achieved at least 8 and 16 weeks of documented continuous cocaine abstinence, respectively, versus 11% and 5% in the drug abuse counseling group.\n This multicomponent behavioral treatment appears to be an effective intervention for retaining outpatients in treatment and establishing cocaine abstinence.", "Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence are efficacious in improving outcomes in substance abusers, but these treatments have rarely been implemented in community-based settings.\n To evaluate the efficacy of an abstinence-based contingency management intervention as an addition to usual care in community treatment settings.\n Random assignment to usual care or usual care plus abstinence-based incentives for 12 weeks.\n Eight community-based outpatient psychosocial drug abuse treatment programs.\n A total of 415 cocaine or methamphetamine users beginning outpatient substance abuse treatment.\n All participants received standard care, and those assigned to the abstinence-based incentive condition also earned chances to win prizes for submitting substance-free urine samples; the chances of winning prizes increased with continuous time abstinent.\n Retention, counseling attendance, total number of substance-free samples provided, percentage of stimulant- and alcohol-free samples submitted, and longest duration of confirmed stimulant abstinence.\n Participants assigned to the abstinence-based incentive condition remained in treatment for a mean +/- SD of 8.0 +/- 4.2 weeks and attended a mean +/- SD of 19.2 +/- 16.8 counseling sessions compared with 6.9 +/- 4.4 weeks and 15.7 +/- 14.4 sessions for those assigned to the usual care condition (P<.02 for all). Participants in the abstinence-based incentive condition also submitted significantly more stimulant- and alcohol-free samples (P<.001). The abstinence-based incentive group was significantly more likely to achieve 4, 8, and 12 weeks of continuous abstinence than the control group, with odds ratios of 2.5, 2.7, and 4.5, respectively. However, the percentage of positive samples submitted was low overall and did not differ between conditions.\n The abstinence-based incentive procedure, which provided a mean of 203 dollars in prizes per participant, was efficacious in improving retention and associated abstinence outcomes.", "In this study, the authors evaluated a low-cost contingency management (CM) procedure for reducing cocaine use and enhancing group therapy attendance in 77 cocaine-dependent methadone patients. Patients were randomly assigned to 12 weeks of standard treatment or standard treatment with CM, in which patients earned the opportunity to win prizes ranging from $1 to $100 for submitting cocainenegative samples and attending therapy. Patients in the CM condition submitted more cocaine-negative samples and attended more groups than patients in standard treatment. The best predictor of cocaine abstinence at follow-up was duration of abstinence during treatment. On average, patients in the CM condition earned $117 in prizes. Data from this study suggest that some aspects of reinforcement can be implemented in group therapy in community-based clinics.\n Copyright (c) 2005 APA, all rights reserved", "Chronic cocaine abuse remains a serious and costly public health problem. This study assessed the effectiveness of a voucher-based reinforcement contingency in producing sustained cocaine abstinence.\n A randomized controlled trial compared voucher-based reinforcement of cocaine abstinence to noncontingent voucher presentation. Patients were selected from 52 consecutively admitted injecting heroin abusers in a methadone maintenance treatment program. Patients with heavy cocaine use during baseline period (N = 37) participated. Except where otherwise indicated, the term cocaine abuse is used in this article in a generic sense and not according to the DSM-III-R definition. Patients exposed to abstinence reinforcement received a voucher for each cocaine-free urine sample (ie, negative for benzoylecgonine) provided three times per week throughout a 12-week period; the vouchers had monetary values that increased as the number of consecutive cocaine-free urine samples increased. Control patients received noncontingent vouchers that were matched in pattern and amount to the vouchers received by patients in the abstinence reinforcement group.\n Patients receiving vouchers for cocaine-free urine samples achieved significantly more weeks of cocaine abstinence (P = .007) and significantly longer durations of sustained cocaine abstinence (P = .001) than controls. Nine patients (47%) receiving vouchers for cocaine-free urine samples achieved between 7 and 12 weeks of sustained cocaine abstinence; only one control patient (6%) achieved more than 2 weeks of sustained abstinence. Among patients receiving vouchers for cocaine-free urine samples, those who achieved sustained abstinence ( > or = 5 weeks) had significantly lower concentrations of benzoylecgonine in baseline urine samples than those who did not achieve sustained abstinence (P < or = .01). Patients receiving voucher reinforcement rated the overall treatment quality significantly higher than controls (P = .002).\n Voucher-based reinforcement contingencies can produce sustained cocaine abstinence in injecting polydrug abusers.", "This study examined whether voucher delivery arrangements affect treatment outcome. First, 90 cocaine-dependent adults were randomly assigned to behavioral counseling or counseling plus vouchers for cocaine-free urine samples. The value of each voucher was low at the beginning but increased as the patient progressed (Voucher Schedule 1). Voucher Schedule 1 produced no improvements relative to counseling only. Next, 23 patients received vouchers on either Voucher Schedule 1 or Voucher Schedule 2. Voucher Schedule 2 began with high voucher values, but requirements for earning vouchers increased as the patient progressed. Average durations of cocaine abstinence were 6.9 weeks on Voucher Schedule 2 versus 2.0 weeks on Voucher Schedule 1 (p = .02). This confirms that vouchers can assist in initiating abstinence and that voucher delivery arrangements are critical.", "Coping skills training, a promising treatment approach for alcoholics, was adapted for use with cocaine abusers and effects on outcome were investigated.\n A cocaine-specific coping skills training (CST) package was compared to an attention placebo control when both were added to a comprehensive treatment program.\n The sites were two private substance abuse treatment facilities, one residential and rural, and one an urban partial hospital.\n Substance abusers in treatment with cocaine abuse or dependence were selected.\n The CST intervention was conducted in individual sessions. It involved functional analysis of high risk situations and coping skills training based on the functional analysis.\n Clients who received CST had significantly fewer cocaine use days and the length of their longest binge was significantly shorter during the 3-month follow-up period compared to clients in the control condition. CST did not affect relapse rates or use of other substances.\n Results support the notion that cocaine-specific CST is a promising adjunct to treatment for cocaine abusers.", "This study evaluated the efficacy of cognitive-behavioral therapy (CBT) and 12-step facilitation (12SF) in treating cocaine abuse. Participants (N = 128) were randomly assigned to treatment conditions and assessed at baseline and at Weeks 4, 8, 12, and 26. Treatment lasted for 12 weeks. It was hypothesized that participants treated with CBT would be significantly more likely to achieve abstinence from cocaine than participants treated with 12SF. A series of patient-treatment matching hypotheses was also proposed. Across 2 different outcome variables, it was found that participants in CBT were significantly more likely to achieve abstinence than participants in 12SF. In addition, some support for matching hypotheses was found, suggesting that both psychotherapies may be differentially effective for identified subgroups of persons that abuse cocaine.", "Ninety-eight male cocaine-dependent patients who completed an intensive outpatient program (IOP) were randomly assigned to either standard group counseling (STND) or individualized relapse prevention (RP) aftercare. Heavier cocaine and alcohol use during IOP and low self-efficacy predicted more cocaine use during the treatment phase of the study, whereas lifetime diagnoses of alcohol dependence, major depression, and any anxiety disorder predicted less cocaine use. Rates of complete abstinence during the 6-month study period were higher in STND than RP, whereas RP was more effective in limiting the extent of cocaine use in those who used during Months 1-3. Matching analyses indicated patients who failed to achieve remission from cocaine dependence during IOP and those with a commitment to absolute abstinence did better in RP than in STND, whereas patients with other abstinence goals did better in STND than RP. Several differences in experiences before cocaine use and \"near-miss\" episodes were also identified.", "To investigate the role of treatment modality in relapse prevention treatment, 32 cocaine-dependent subjects were randomly assigned by cohorts to group-based relapse prevention (G-RP) or individually based RP (I-RP). The two RP formats were identical in content, consisting of 12 outpatient treatment sessions over a 2-month period immediately following hospitalization. The proportion of subjects providing cocaine-free urines at the end of RP treatment did not differ between formats; however, G-RP subjects reported using cocaine on significantly fewer days during treatment, and experiencing fewer cocaine-related problems than did I-RP subjects. Follow-up data collected at 12 and 24 weeks' posttreatment revealed no significant differences between RP formats on any cocaine-use outcome measures. Regardless of therapy format. RP treatment was related to statistically significant and sustained improvements in other areas of psychosocial functioning, including addiction severity, coping, and craving for cocaine. The overall findings suggest that the efficacy of relapse prevention training is not limited by therapy format.", "This was a multicenter investigation examining the efficacy of 4 psychosocial treatments for cocaine-dependent patients.\n Four hundred eighty-seven patients were randomly assigned to 1 of 4 manual-guided treatments: individual drug counseling plus group drug counseling (GDC), cognitive therapy plus GDC, supportive-expressive therapy plus GDC, or GDC alone. Treatment was intensive, including 36 possible individual sessions and 24 group sessions for 6 months. Patients were assessed monthly during active treatment and at 9 and 12 months after baseline. Primary outcome measures were the Addiction Severity Index-Drug Use Composite score and the number of days of cocaine use in the past month.\n Compared with the 2 psychotherapies and with GDC alone, individual drug counseling plus GDC showed the greatest improvement on the Addiction Severity Index-Drug Use Composite score. Individual group counseling plus GDC was also superior to the 2 psychotherapies on the number of days of cocaine use in the past month. Hypotheses regarding the superiority of psychotherapy to GDC for patients with greater psychiatric severity and the superiority of cognitive therapy plus GDC compared with supportive-expressive therapy plus GDC for patients with antisocial personality traits or external coping style were not confirmed.\n Compared with professional psychotherapy, a manual-guided combination of intensive individual drug counseling and GDC has promise for the treatment of cocaine dependence.", "This study evaluated a novel drug abuse treatment, the Therapeutic Workplace. In this treatment, patients are paid to perform jobs or to participate in job training. Salary is linked to abstinence by requiring patients to provide drug-free urine samples to gain access to the workplace. Pregnant and postpartum drug abuse patients (N = 40) were randomly assigned to a Therapeutic Workplace or usual care control group. Therapeutic Workplace participants were invited to work 3 hr every weekday for 6 months and could earn up to $4,030 in vouchers for abstinence, workplace attendance, and performance. On average, 45% of participants attended the workplace per day. Relative to controls, the Therapeutic Workplace nearly doubled patients' abstinence from opiates and cocaine (33% vs. 59% of thrice-weekly urine samples drug negative, respectively, p < .05). The Therapeutic Workplace can effectively treat heroin and cocaine abuse in pregnant and postpartum women.", "This study assessed whether contingent incentives can be used to reinforce cocaine abstinence in dependent outpatients. Seventy cocaine-dependent outpatients were randomized into 2 conditions. All participants received 24 weeks of treatment and 1 year of follow-up. The treatment provided to all participants combined counseling based on the community reinforcement approach with incentives in the form of vouchers exchangeable for retail items. In 1 condition, incentives were delivered contingent on cocaine-free urinalysis results, whereas in the other condition incentives were delivered independent of urinalysis results. Abstinence-contingent incentives significantly increased cocaine abstinence during treatment and 1 year of follow-up compared with noncontingent incentives.", "To examine the contributions of community reinforcement therapy to outcome in the community reinforcement approach (CRA) + vouchers outpatient treatment for cocaine dependence.\n One hundred cocaine-dependent outpatients were randomly assigned to one of 2 treatment conditions: CRA + vouchers or vouchers only. All patients earned incentives in the form of vouchers exchangeable for retail items contingent on cocaine-free urinalysis results during treatment weeks 1 to 12. Incentives were combined with a 24-week course of CRA therapy designed to promote healthy lifestyle changes in the CRA + vouchers condition, while incentives represented the primary treatment in the vouchers-only condition. Patient drug use and psychosocial functioning were assessed at intake and at least every 3 months for 2 years after treatment entry.\n Patients treated with CRA + vouchers were retained better in treatment, used cocaine at a lower frequency during treatment but not follow-up, and reported a lower frequency of drinking to intoxication during treatment and follow-up compared with patients treated with vouchers only. Patients treated with CRA + vouchers also reported a higher frequency of days of paid employment during treatment and the initial 6 months of follow-up, decreased depressive symptoms during treatment only, and fewer hospitalizations and legal problems during follow-up.\n Combining CRA with vouchers had therapeutic effects on substance abuse and psychosocial functioning during treatment and posttreatment follow-up in cocaine-dependent outpatients, although effects on cocaine use appear to be limited to the treatment period." ]

[ "17360794", "17264106", "15130977", "17156264", "15955759", "18834368", "16102151", "9869250", "17612998", "10582982", "15573828", "3176084", "9086985" ]

[ "Randomised trial of a computer-generated tailored written education package for patients following stroke.", "Stress in caregivers of aphasic stroke patients: a randomized controlled trial.", "Training carers of stroke patients: randomised controlled trial.", "Effects of an individualized multimedia computer program for health education in patients with a recent minor stroke or transient ischemic attack - a randomized controlled trial.", "The impact of stroke nurse specialist input on risk factor modification: a randomised controlled trial.", "Control of modifiable risk factors in ischemic stroke outpatients by pharmacist intervention: an equal allocation stratified randomized study.", "The impact of a nurse-led support and education programme for spouses of stroke patients: a randomized controlled trial.", "The impact of an information pack on patients with stroke and their carers: a randomized controlled trial.", "Recovery from disability after stroke as a target for a behavioural intervention: results of a randomized controlled trial.", "Randomized controlled trial of a comprehensive stroke education program for patients and caregivers.", "A randomized trial to evaluate an education programme for patients and carers after stroke.", "Family intervention after stroke: does counseling or education help?", "The potential utility of a shared medical record in a \"first-time\" stroke population." ]

[ "The ideal method of providing stroke patients with information has not been established.\n To evaluate the effectiveness of providing stroke patients with computer-generated tailored written information.\n Randomised controlled trial with blinded assessor.\n Acute stroke unit.\n 138 stroke patients.\n Patients were randomised to receive either computer-generated tailored written information about stroke or generic written information while in hospital. Three months following discharge, a blinded assessor evaluated the outcomes of knowledge about stroke, self-efficacy (Self-Efficacy to Perform Self-Management Behaviours Scale), anxiety and depression (Hospital Anxiety and Depression (HAD) Scale), perceived health status (COOP charts), satisfaction with content and presentation of the written information received (separate 10-point visual analogue scale for content and presentation), and desire for additional information.\n Complete data were obtained for 133 (96.4%) patients. Patients in the intervention group were significantly more satisfied with the content (difference on a 10-point visual analogue scale was 1, 95% confidence interval 0.4 to 1.7, P = 0.003) and presentation (difference on a 10-point visual analogue scale was 1.2, 95% confidence interval 0.6 to 1.9, P < 0.001). Significantly, fewer patients in the intervention group desired additional information about stroke at follow-up than patients in the control group (4.5% versus 32.8%; P < 0.001). Anxiety change scores improved slightly more in favour of the control group (1.4 difference on the HAD subscale, 95% confidence interval 0.2 to 2.8, P = 0.03). No significant differences between the groups were observed for any of the other outcome measures.\n Providing stroke patients with computer-generated tailored written information improved satisfaction with the information that was received and was more effective in meeting patients' informational needs than non-tailored information, but had no effect on knowledge about stroke, self-efficacy, depression, or perceived health status.", "Communication difficulties due to aphasia following stroke are particularly stressful to caregivers.\n To examine the impact of a psychoeducation programme on caregivers' burden and stress and communication between the caregiver and aphasic stroke patient.\n Randomized wait-list controlled trial with immediate or three-month delayed treatment.\n Three public hospital rehabilitation services in Sydney, Australia.\n Thirty-nine caregivers of aphasic stroke patients, up to 12 months post stroke: 19 given immediate treatment and 20 in a delayed treatment control group.\n Four-session weekly caregiver programme that included elements of education, support and communication skills conducted by a speech pathologist, social worker and clinical psychologist.\n The General Health Questionnaire (GHQ) was used to measure caregiver stress, the Relatives' Stress Scale was used to measure caregiver burden and a communication questionnaire was designed specifically for this project.\n Thirty-one caregivers completed the study. Caregivers in the immediate treatment group had significant reductions in GHQ measured stress (GHQ mean (SD) at baseline= 6.26 (5.67), GHQ post treatment 3.21 (SD 4.20), P = 0.006). There was no improvement in wait-listed caregivers. Improvement was not maintained at three-month follow-up. There were no significant effects of the programme on communication skills or on caregiver burden.\n Stroke caregiver support, education and training programmes have short-term effects on caregiver stress levels but are likely to require ongoing involvement to maintain their effect.", "Informal care givers support disabled stroke patients at home but receive little training for the caregiving role.\n To evaluate the effectiveness of training care givers in reducing burden of stroke in patients and their care givers.\n A single, blind, randomised controlled trial.\n Stroke rehabilitation unit.\n 300 stroke patients and their care givers.\n Training care givers in basic nursing and facilitation of personal care techniques.\n Cost to health and social services, caregiving burden, patients' and care givers' functional status (Barthel index, Frenchay activities index), psychological state (hospital anxiety and depression score), quality of life (EuroQol visual analogue scale) and patients' institutionalisation or mortality at one year.\n Patients were comparable for age (median 76 years; interquartile range 70-82 years), sex (53% men), and severity of stroke (median Barthel index 8; interquartile range 4-12). The costs of care over one year for patients whose care givers had received training were significantly lower (10,133 pounds sterling v 13,794 pounds sterling (18,087 dollars v 24,619 dollars; 15,204 euros v 20,697 euros); P = 0.001). Trained care givers experienced less caregiving burden (care giver burden score 32 v 41; P = 0.0001), anxiety (anxiety score 3 v 4; P = 0.0001) or depression (depression score 2 v 3; P = 0.0001) and had a higher quality of life (EuroQol score 80 v 70; P = 0.001). Patients' mortality, institutionalisation, and disability were not influenced by caregiver training. However, patients reported less anxiety (3 v 4.5; P < 0.0001) and depression (3 v 4; P < 0.0001) and better quality of life (65 v 60; P = 0.009) in the caregiver training group.\n Training care givers during patients' rehabilitation reduced costs and caregiver burden while improving psychosocial outcomes in care givers and patients at one year.", "Transient ischemic attack (TIA) and stroke patients often show a striking lack of knowledge about their disease. We developed a computer program that provided health education fitting the educational level, risk profile and symptoms of patients and evaluated it in a randomized controlled trial.\n Transient ischemic attack or minor stroke patients were allocated to health education by a physician (n = 32) or to a combination of education by a physician and the computer program (n = 33). Knowledge was tested by means of a questionnaire at 1 and 12 weeks after inclusion. The maximum possible score was 71 points.\n Overall knowledge was low - the mean score was 43.6 at 1 week and 42.0 points at 12 weeks for both the groups. The intervention group had slightly better scores at 1 week after using the computer program, 45.4 vs 41.5 (P = 0.09), with the difference increasing to 4.3 points after (post-hoc) adjustment for age and level of education (P = 0.06). After 12 weeks, the score in the intervention group dropped significantly to 42.0 points (P = 0.05), and was no longer different from the standard group.\n This study did not show a lasting effect of health education by an individualized computer program on the knowledge of TIA and minor stroke patients.", "nan", "To evaluate the adequacy of management of modifiable risk factors (MRF) in a group of ischemic stroke outpatients and the value of pharmacist intervention in a randomized controlled study in a tertiary referral hospital.\n 160 ischemic stroke outpatients from the same catchment area and with the same financial arrangements for healthcare, went through a 6-month equal allocation stratified randomized study. Routine practice was not altered except for a monthly 1-hour pharmacist-intervention education programme. We evaluated the differences in blood pressure (BP), blood glucose and lipid profiles before and after study. The proportion of patients with adequate management of MRF was studied.\n There were no differences in the demographic characteristics, MRF and medications prescribed throughout the study. Before the study, the proportions of adequate control of BP in the control and intervention groups were 43% vs. 40% (P = 0.64), lipid 27% vs. 13% (P = 0.09) and glucose 36% vs. 21% (P = 0.15) . At the end of the study, the corresponding proportions were for BP 43% vs. 83% (P = 0.00), lipid 27% vs. 40% (P = 0.16) and glucose 46% vs. 35% (P = 0.40).\n Pharmacist intervention was associated with improved BP control but not with the other MRF. Earlier initiation and longer duration of intervention may improve the outcome further, and whether targeting of high-risk subjects may be particularly rewarding is worthy of investigation.", "The aim of the present study was to determine the impact of a nurse-led support and education programme for improving the spouses' perceived general quality of life, life situation, general well-being and health state.\n Stroke is a disease with great consequences for the patients and their families. The spouses often feel obligated to care for the patient, providing psychological and physical support and having to cope with the patient's physical and cognitive impairments. This might lead to increased problems, as family members struggle to adapt to their new roles and responsibilities.\n Longitudinal, randomized controlled trial. One hundred spouses were randomly assigned to intervention or control groups, 50 in each group. The intervention group participated in a support and education programme, six times during six months, led by stroke specialist nurses. Both groups were followed for 12 months.\n No significant differences were found, between intervention and control groups, over time. In the sub analyses, we found that the group attending 5-6 times had a significant decrease in negative well-being and increased quality of life over time, while the group attending fewer times had a significant decrease in positive well-being and health state, similar to the control group, which also had a significant decrease in negative and general well-being.\n A support and education programme might have a positive effect on spouses' well-being, on condition that they attend at least five times.\n To facilitate the spouses' role as informal caregivers to the stroke patients, further development of the support and education programme used in the present study is needed, including empowerment approach and implementation of coping strategies.", "To assess the impact of information packs on patients with stroke and their carers, and to pilot some of the methodology for a trial of a Family Support Organiser (FSO).\n Seventy-one patients admitted to Oxford hospitals with acute stroke during February-July 1995, and 49 informal carers of these patients.\n Randomized controlled trial. Intervention group received an Information pack containing various Stroke Association publications one month after their stroke, or at discharge from hospital, whichever was sooner. Control group received nothing. Follow-up was by interview at the place of residence of the patients six months after their stroke.\n Outcome measures assessed knowledge about stroke; satisfaction with information received; patient behaviour in terms of access to community services and benefits; and health status and quality of life.\n Patients and carers in the intervention group tended to know more about stroke, but these differences were not significant once adjusted for age. Patients in the intervention group (but not carers) tended to be more satisfied with the information that they had received, but the differences were not significant. There were no differences with regard to any aspects of quality of life in patients in the intervention group, though carers in the intervention group were found to have significantly better mental health (p = 0.04).\n While the study was too small to generate firm conclusions, information leaflets may lead to improved knowledge about stroke several months after they have been distributed. This finding is worth following up with larger studies. The stroke knowledge questionnaire that was piloted in this trial seems to be able to detect differences between groups.", "Disability following stroke is highly prevalent and is predicted by psychological variables such as control cognitions and emotions, in addition to clinical variables. This study evaluated the effectiveness of a workbook-based intervention, designed to change cognitions about control, in improving outcomes for patients and their carers.\n At discharge, stroke patients were randomly allocated (with their carers) to a 5-week intervention (n = 103) or control (normal care: n = 100). The main outcome (at 6 months) was recovery from disability using a performance measure, with distress and satisfaction as additional outcomes.\n The intervention group showed significantly better disability recovery, allowing for initial levels of disability, than those in the control group, F(1,201) = 5.61, p = 0.019. Groups did not differ in distress or satisfaction with care for patients or carers. The only psychological process variable improved by the intervention was Confidence in Recovery but this did not mediate the effects on recovery.\n A large proportion of intervention participants did not complete the workbook tasks. This was perhaps associated with the fairly low level of personal contact with workbook providers. The modest success of this intervention suggests that it may be possible to develop effective behavioural interventions to enhance recovery from disability in stroke patients.", "We report the findings of a randomized controlled trial to determine the effectiveness of a multidisciplinary Stroke Education Program (SEP) for patients and their informal carers.\n Two hundred four patients admitted with acute stroke and their 176 informal carers were randomized to receive an invitation to the SEP or to receive conventional stroke unit care. The SEP consisted of one 1-hour small group educational session for inpatients followed by six 1-hour sessions after discharge. The primary outcome measure was patient- and carer-perceived health status (SF-36) at 6 months after stroke. Knowledge of stroke, satisfaction with services, emotional outcome, disability, and handicap and were secondary outcome measures.\n Only 51 of 108 (47%) surviving patients randomized to the SEP completed the program, as did 20 of 93 (22%) informal carers of surviving patients. Perceived health status (Short Form 36 [SF-36] health survey) scores were similar for SEP patients and controls. Informal carers in the control group scored better on the social functioning component of the SF-36 than the SEP group (P=0.04). Patients and informal carers in the SEP group scored higher on the stroke knowledge scale than controls (patients, P=0.02; carers, P=0. 01). Patients in the SEP group were more satisfied with the information that they had received about stroke (P=0.004). There were no differences in emotional or functional outcomes between groups.\n Although the SEP improved patient and informal carer knowledge about stroke and patient satisfaction with some components of stroke services, this was not associated with an improvement in their perceived health status. Indeed, the social functioning of informal carers randomized to the SEP was less than in the control group.", "To evaluate the effectiveness of an education programme for patients and carers recovering from stroke.\n Randomized controlled trial.\n One hundred and seventy patients admitted to a stroke rehabilitation unit and 97 carers of these patients.\n The intervention group received a specifically designed stroke information manual and were invited to attend education meetings every two weeks with members of their multidisciplinary team. The control group received usual practice.\n Primary outcome was knowledge of stroke and stroke services. Secondary outcomes were handicap (London Handicap Scale), physical function (Barthel Index), social function (Frenchay Activities Index), mood (Hospital Anxiety and Depression Scale) and satisfaction (Pound Scale). Carer mood was measured by the General Health Questionnaire-28.\n There was no statistical evidence for a treatment effect on knowledge but there were trends that favoured the intervention. The education programme was associated with a significantly greater reduction in patient anxiety score at both three months (p =0.034) and six months (p =0.021) and consequently fewer 'cases' (Hospital Anxiety and Depression Scale anxiety subscale score > or =11). There were no other significant statistical differences between the patient or carer groups for other outcomes, although there were trends in favour of the education programme.\n An education programme delivered within a stroke unit did not result in improved knowledge about stroke and stroke services but there was a significant reduction in patient anxiety at six months post stroke onset.", "Two interventions for improving stroke caregiver knowledge, stabilizing family function, promoting patient adjustment, and enlisting the use of social resources after stroke were compared with routine medical and nursing care of stroke patients (n = 61) at a 440-bed Veterans Administration Medical Center. The education intervention (n = 64) consisted of classroom instruction for caregivers about basic stroke care principles. The counseling condition (n = 63) consisted of education plus seven follow-up problem-solving sessions with a social worker (for the caregiver). Six months and 1 year after the stroke, both interventions significantly improved caregiver knowledge and stabilized some aspects of family function better than routine care. Counseling was consistently more effective than education alone and resulted in better patient adjustment at 1 year. Neither intervention influenced the use of social resources.", "This preliminary investigation explored the utilization of a shared medical record for improving treatment compliance and outcome measures for \"first-time\" stroke victims. It was hypothesized that individuals who had access to information regarding the diagnosis and treatment of their stroke and general stroke-related educational materials would have improved compliance and outcomes when compared with persons with only educational materials. Inpatient teaching was reinforced during outpatient visits. Data were collected at two points in time, comparing the two groups. Chi-square tests showed no differences between the shared-record and control groups regarding baseline demographic characteristics. Subjects reported their intentions to modify health-related behaviors by completing the diet, smoking and medication subscales of Miller's Health Intention Scale. They reported their compliance with treatment on the diet, medication, and smoking subscales of Miller's Health behavior Scale. The Glasgow Outcome Scale and the Global Outcome provided treatment outcome measures. Analysis of outcome measures was performed by means of analysis of variance. At the 6-month follow-up, no differences were seen in health practices. A trend toward better perceived outcome was suggested in the shared medical record group when poorest perceived outcomes were compared. For the most part, subjects in the shared-record group were satisfied with having a copy of their records, took them on visits to physicians, and reported learning more about their strokes. Suggestions for future research include specific treatment information as a variable to be assessed against better measures of health practices. In particular, studies might investigate whether access to personal health and treatment information interacts with the amount of responsibility patients take for their own health and whether this leads to the development of a collaborative relationship with primary health care professionals." ]

[ "12502670", "14514347" ]

[ "Metformin as an adjunct therapy in adolescents with type 1 diabetes and insulin resistance: a randomized controlled trial.", "Metformin as additional therapy in adolescents with poorly controlled type 1 diabetes: randomised placebo-controlled trial with aspects on insulin sensitivity." ]

[ "To evaluate whether, in adolescents with type 1 diabetes, the addition of metformin to insulin and standard diabetes management results in 1) higher insulin sensitivity and 2) lower HbA1c, fasting glucose, insulin dosage (units per kilogram per day) and BMI.\n This was a randomized, placebo-controlled 3-month trial of metformin therapy in 27 adolescents with type 1 diabetes, high insulin dosage (>1 unit. kg(-1). day(-1)), and HbA1c >8%, with measurements of insulin sensitivity (by frequently sampled intravenous glucose tolerance test [FSIGT]), HbA1c, insulin dosage, and BMI at the onset and end of treatment.\n At t = 0, HbA1c was 9.2 +/- 0.9%, insulin dosage was 1.2 +/- 0.2 units. kg(-1). day(-1), fasting glucose was 10.6 +/- 2.4 mmol/l, and BMI was 24.2 +/- 3.9 kg/m2 (means +/- SD), with no difference between the metformin and placebo groups. At the end of the study, HbA1c was 0.6% lower in the metformin group than in the placebo group (P < 0.05). This was achieved at lower daily insulin dosages (metformin group -0.14 +/- 0.1 vs. placebo group 0.02 +/- 0.2 units. kg(-1). day(-1); P < 0.05), with no significant change in BMI. Fasting glucose levels improved significantly in the metformin group (P < 0.05). Change in insulin sensitivity, measured by FSIGT, was not significantly different between the two groups at study end. Mild hypoglycemia occurred more frequently in the metformin-treated than in the placebo subjects (1.75 +/- 0.8 vs. 0.9 +/- 0.4 events. patient(-1). week(-1); P = 0.03). There were no differences in frequency of severe hypoglycemic episodes or gastrointestinal complaints between the two groups.\n Metformin treatment lowered HbA1c and decreased insulin dosage with no weight gain in teens with type 1 diabetes in poor metabolic control. Changes in insulin sensitivity were not documented in this study using the FSIGT. Long-term studies will determine whether these improvements are sustained and whether certain subgroups accrue greater benefit from this therapy.", "Metabolic control often deteriorates during puberty in children with type 1 diabetes. The aim of the present study was to investigate whether addition of metformin for 3 Months improves metabolic control and insulin sensitivity.\n Twenty-six of 30 randomised adolescents with type 1 diabetes (18 females, eight males) completed a double-blind placebo-controlled trial. Their mean age was 16.9+/-1.6 (s.d.) Years, mean glycated haemoglobin (HbA(1c)) 9.5+/-1.1% and daily insulin dosage 1.2+/-0.3 U/kg. The participants were randomised to receive oral metformin or placebo for 3 Months. HbA(1c) was measured Monthly, and peripheral insulin sensitivity was assessed by a euglycaemic hyperinsulinaemic clamp at baseline and at the end of the study.\n HbA(1c) decreased significantly in the group treated with metformin, from 9.6 to 8.7% (P<0.05), but was unchanged in the placebo group (9.5 vs 9.2%). Peripheral glucose uptake divided by mean plasma insulin concentration was increased in the metformin group (P<0.05) but not in the placebo group. Initial insulin sensitivity was inversely correlated to changes in HbA(1c) (r=-0.62; P<0.05) and positively correlated to changes in insulin sensitivity (r=0.77; P<0.01).\n In this double-blind placebo-controlled study we found that metformin improves metabolic control in adolescents with type 1 diabetes. The effect seems to be associated with an increased insulin-induced glucose uptake." ]

[ "17127226", "1348797", "4032549", "848927", "2199628", "3908009" ]

[ "A pilot study on prevention of catheter-related urinary tract infections with fluoroquinolones.", "Prophylactic ciprofloxacin for catheter-associated urinary-tract infection.", "Short-term versus prolonged systemic antibiotic prophylaxis in patients treated with indwelling catheters.", "Antimicrobial prophylaxis for catheter-associated bacteriuria.", "A single dose of aztreonam in the prevention of urinary tract infections in elderly catheterized patients.", "Prophylactic single-dose co-trimoxazole for prevention of urinary tract infection after abdominal hysterectomy." ]

[ "The objective of this multicenter, randomized, controlled, parallel group trial was to evaluate the efficacy of levofloxacin 250 mg oral, once daily (LVFX), placebo one tablet oral once daily (Placebo [P] group) and ciprofloxacin (CPFX) 500 mg oral, twice daily (single blind), prophylaxis in preventing bacteriuria (> or = 10(3) CFU/ml) in post-surgical catheterized patients. In the modified intention-to-treat (M-ITT) population of the 82 enrolled patients, negative bacteriuria was observed in 92% of LVFX group, in 80% of P group and in 100% of CPFX group while in the per-protocol (PP) population figures were: 100%, 86.4% and 100% respectively. Only one symptomatic urinary tract infection and one surgical wound infection were observed in the P group. Both drugs were well tolerated, showing a safety profile comparable to placebo. The high frequency of negative bacteriuria in the placebo group sounds encouraging as it underlines that the adoption of closed urinary drainage system catheters in hospital setting may reduce the frequency of hospital-acquired infections.", "Patients receiving antibiotics during bladder drainage have a lower incidence of urinary-tract infections compared with similar patients not on antibiotics. However, antibiotic prophylaxis in patients with a urinary catheter is opposed because of the fear of inducing resistant bacterial strains. We have done a double-blind, placebo-controlled trial of prophylactic ciprofloxacin in selected groups of surgical patients who had postoperative bladder drainage scheduled to last for 3 to 14 days. Patients were randomly assigned to receive placebo (n = 61), 250 mg ciprofloxacin per day (n = 59), or 500 mg ciprofloxacin twice daily (n = 64) from postoperative day 2 until catheter removal. 75% of placebo patients were bacteriuric at catheter removal compared with 16% of ciprofloxacin-treated patients (relative risk [RR] [95% CI] 4.7 [3.0-7.4]). The prevalence of pyuria among placebo patients increased from 11% to 42% while the catheter was in place; by contrast, the rate of pyuria was 11% or less in patients receiving ciprofloxacin (RR 4.0 [2.1-7.3]). 20% of placebo patients had symptomatic urinary-tract infections, including 3 with septicaemia, compared with 5% of the ciprofloxacin groups (RR 4.0 [1.6-10.2]). Bacteria isolated from urines of placebo patients at catheter removal were mostly species of enterobacteriaceae (37%), staphylococci (26%), and Enterococcus faecalis (20%), whereas species isolated from urines of ciprofloxacin patients were virtually all gram-positive. Ciprofloxacin-resistant mutants of normally sensitive gram-negative bacteria were not observed. Ciprofloxacin prophylaxis is effective and safe in the prevention of catheter-associated urinary tract infection and related morbidity in selected groups of patients requiring 3 to 14 days of bladder drainage.", "Newly hospitalized patients with stroke treated by indwelling catheters were assigned randomly to 3 treatment groups. Group 1 (24 patients) received 3 gm. ampicillin intramuscularly in divided doses 1 hour before, at the time of and 6 hours after insertion of the catheter. Group 2 (28 patients) received daily 1 gm. ampicillin intramuscularly every 8 hours. Group 3 (26 patients) was not subjected to any antimicrobial prophylaxis. Within 1 week after catheter insertion significant bacteriuria developed in 12.5 per cent of the patients in group 1, 42.8 per cent in group 2 and 45.1 per cent in group 3. The difference in the incidence between group 1 and either group 2 or 3 was statistically significant (p less than 0.02 and p less than 0.01, respectively). The mean number of strains (plus or minus standard error of mean) isolated per case of bacteriuria in group 3 (1.25 plus or minus 0.18) was significantly lower (p less than 0.05) and antimicrobial resistant strains were fewer (4 of 15) than in group 2 (1.75 plus or minus 0.13 and 12 of 21, respectively).", "We evaluated short-term systemic antimicrobial prophylaxis for catheter-associated bacteriuria in women undergoing elective gynecological operations in a prospective, controlled, double-masked study. Nine of 100 placebo-treated patients acquired bacteriuria during catheterization compared with 3 of 96 of the drug-treated group. However, at the time of hospital discharge, clean-voided urine specimens were positive as frequently in the drug-treated group (8 of 82 patients cultured) as in the placebo group (8 of 75 patients cultured). No difference in febrile morbidity due to bacteriuria was noted between the prophylaxis and placebo groups. The incidence of catheter-associated bacteriuria may be reduced by antimicrobial prophylaxis. However, because the protective effect is transient and is associated with the selection of resistant organisms, prophylaxis is not indicated for patients at low risk for acquired bacteriuria and in whom the sequelae of catheter-associated infections are infrequent.", "We have compared the effects of aztreonam and placebo in the prevention of urinary tract infections (UTI) in elderly hospitalized patients who needed urethral catheterization. 162 patients (96 males, 66 females; age range 60-91 years) were randomly allocated to receive double-blind a single dose of aztreonam (2 g i.m. 80 patients) or placebo (4 ml lidocaine 2%, 82 patients) three hours before catheterization. All patients were followed-up for 7 days. Urine culture was performed before, at the first, third and seventh day of catheterization. At the end of follow-up 71/80 patients (88.7%) who received a single preventing dose of aztreonam had negative urine culture without clinical signs of UTI. On the contrary, in the group treated with placebo at the end of follow-up only 38/82 patients (46.3%) had negative urine without clinical signs of UTI. In conclusion, our data suggest that a single 2g i.m. dose of aztreonam is effective in preventing UTI in elderly patients needing indwelling urethral catheterization.", "The efficacy of a preoperative single-dose of co-trimoxazole in reducing postoperative urinary tract infection and febrile morbidity after abdominal hysterectomy was evaluated in a randomized placebo-controlled study of 90 patients undergoing surgery. Among the co-trimoxazole patients, 6.2% developed urinary tract infection compared to 31% in the placebo group (p less than 0.001) and 12.5% febrile morbidity compared to 38% in the placebo patients (p less than 0.025). No adverse side effects of co-trimoxazole were observed and this regimen seems both safe and effective." ]

[ "15126706", "15089024" ]

[ "The role of stretching in rehabilitation of hamstring injuries: 80 athletes follow-up.", "A comparison of 2 rehabilitation programs in the treatment of acute hamstring strains." ]

[ "For years, stretching has been an integral part of fitness, practice, and rehabilitation programs to decrease muscle stiffness and relieve pain associated with it. The increased joint range of motion (ROM), indicating the degree of muscle flexibility, has a benefit of stretching proven for healthy tissues.\n The objective of our study was the assessment of the effects of stretching in the rehabilitation of hamstring injuries.\n We followed up 80 Greek athletes, of average age 20.5 yr, with \"second-degree\" strain of the hamstring muscles. The athletes were divided into two groups, A and B. For both groups, we estimated the time required for the rehabilitation of the decreased knee ROM and the total time before the athletes could return to a full training program.\n Group B, which carried out a more intensive stretching program, was found to have a statistically significant shorter time of regaining normal ROM (5.57 +/- 0.71 d) and rehabilitation period (13.27 +/- 0.71 d) in comparison with group A (7.32 +/- 0.525 d and 15.05 +/- 0.81 d, respectively).\n Our results suggest that stretching is of great importance in treating muscle strain injuries in that it improves the effectiveness of the rest rehabilitation program.", "Prospective randomized comparison of 2 rehabilitation programs.\n The objectives of this study were to compare the effectiveness of 2 rehabilitation programs for acute hamstring strain by evaluating time needed to return to sports and reinjury rate during the first 2 weeks and the first year after return to sport. A third objective was to investigate the relationship between functional testing performance and time to return to sports and reinjury rates after return to sport.\n Hamstring muscle strains are common in sports and often result in chronic pain, recurrent hamstring strains, and reduced sports performance. Current rehabilitation programs are primarily developed anecdotally and lack support from prospective, randomized research.\n Twenty-four athletes with an acute hamstring strain were randomly assigned to 1 of 2 rehabilitation groups. Eleven athletes were assigned to a protocol consisting of static stretching, isolated progressive hamstring resistance exercise, and icing (STST group). Thirteen athletes were assigned to a program consisting of progressive agility and trunk stabilization exercises and icing (PATS group). The number of days for full return to sports, injury recurrence within the first 2 weeks, injury recurrence within the first year of returning to sports, and lower-extremity functional evaluations were collected for all subjects and compared between groups.\n The average (+/- SD) time required to return to sports for athletes in the STST group was 37.4 +/- 27.6 days, while the average time for athletes in the PATS group was 22.2 +/- 8.3 days. This difference was not statistically significant (P = .2455). In the first 2 weeks after return to sports, reinjury rate was significantly greater (P = .00343, Fisher's exact test) in the STST group, where 6 of 11 athletes (54.5%) suffered a recurrent hamstring strain after completing the stretching and strengthening program, as compared to none of the 13 athletes (0%) in the PATS group. After 1 year of return to sports, reinjury rate was significantly greater (P = .0059, Fisher's exact test) in the STST group. Seven of 10 athletes (70%) who completed the hamstring stretching and strengthening program, as compared to only 1 of the 13 athletes (7.7%) who completed the progressive agility and trunk stabilization program, suffered a recurrent hamstring strain during that 1-year period.\n A rehabilitation program consisting of progressive agility and trunk stabilization exercises is more effective than a program emphasizing isolated hamstring stretching and strengthening in promoting return to sports and preventing injury recurrence in athletes suffering an acute hamstring strain. Future randomized clinical trials should investigate the potential for progressive agility and trunk stabilization programs in the prevention of hamstring strain injury during sports." ]

[ "21077522", "2731771", "19016569", "15842277", "3946501" ]

[ "Evaluation of the feasibility of a new method for performing chorion villus sampling.", "Transcervical chorionic villi sampling: a comparison between the silver cannula and the Portex catheter.", "A randomized study to assess two different techniques of aspiration while performing transabdominal chorionic villus sampling.", "A randomised controlled trial of biopsy forceps and cannula aspiration for transcervical chorionic villus sampling.", "A randomized study of three cannulas for transcervical chorionic villus sampling." ]

[ "This study aimed to evaluate the usefulness and safety of a new method for taking a placental biopsy.\n The procedures were performed using the traditional single needle technique (group 1) or the new method (group 2). In group 2, the piston was fixed in a simple metallic clip and the negative pressure was maintained in a continuous manner which was controlled with a three-way stopcock.\n Multiple uterine insertion was necessary in 14 cases (32.6%) in group 1 and five (11.9%) in group 2 (p < 0.05). The amount of chorionic tissue obtained was significantly higher in group 2 (19.1 +/- 15.0 mg vs. 33.9 +/- 17.4 mg p < 0.05). The abortion rates did not differ in either group.\n While using this technique, the operator is capable of performing the procedure without any assistance and of applying constant negative pressure only in the placenta. The advantageous outcomes are probably related to the size as well as the incessant fashion of the vacuum force.", "The Portex catheter and the silver cannula are two of the most widely used biopsy devices for chorionic villus sampling. In a prospective randomized study we used these two devices alternatively in 168 women. Significantly more trophoblastic tissue was obtained with the silver cannula than with the Portex catheter (p less than 0.05) while significantly more failures to obtain villus tissue were recorded with the Portex cannula (8/84 with the silver cannula vs. 19/84 with the Portex cannula; p less than 0.05). In 27 cases where use of the device met with failure to obtain chorionic villi after three attempts the other instrument was then used in the same patient (combined group). Four pregnancies aborted spontaneously after the procedure (2.4%). Significantly more complications occurred in the 'combined' group (4/27 vs. 4/168, p less than 0.05). A higher yield of trophoblastic tissue is possible with the silver cannula than with the Portex catheter.", "The technique used to perform transabdominal chorionic villus sampling (CVS) is not standardized, but aspiration of villi is generally obtained by discontinuous vacuum created in a syringe, manually or by a hand-grip device. We evaluated the feasibility of a new method of performing CVS which employs a 4-mL Vacutainer connected to the needle, producing a continuous negative pressure.\n Two hundred pregnant women, whose gestational age ranged from 10 + 2 to 16 + 2 (mean, 12 + 1) weeks, entered the randomized study, which was powered to detect with 90% probability the absence of any difference in the size of chorionic samples obtained by using a 20-mL syringe with the vacuum obtained by a hand-grip device (Group 1) or by a vacutainer (Group 2). Four operators with different levels of experience performed all the procedures, which were done transabdominally using a freehand technique with a 20-gauge needle under ultrasound guidance.\n Maternal age, body mass index, gestational age and the way the needle was inserted within the chorion were similar in the two groups. The median amount of villi sampled was 20 mg, with no differences between the two groups. The rate of fetal loss was 1.7%. All losses occurred in women of Group 1 who had only one needle insertion. A second needle insertion was required more frequently while using the vacutainer.\n This new technique for performing transabdominal CVS uses a readily available device and is as effective as traditional sampling systems to aspirate villi. It has the advantage of being a one-operator procedure.", "This trial compared two instruments for transcervical chorionic villus sampling (CVS).\n Randomised controlled trial.\n Regional university prenatal diagnosis and treatment centre.\n Two hundred women were randomised at 10(+0)-12(+6) weeks of gestation to transcervical CVS using cannula aspiration (CA) or biopsy forceps (BF).\n Women undergoing indicated CVS signed informed consent. Randomisation after decision to perform transcervical CVS.\n Primary outcome: the rise in maternal serum alpha-fetoprotein (alpha-FP). Secondary outcomes: (i) placental trauma (fetomaternal haemorrhage [FMH]); (ii) laboratory, procedure, and cytogenetic results and pregnancy outcomes; (iii) patient and operator satisfaction; and (iv) economic analyses. Analyses were performed by intention to treat.\n The -FP rise did not differ between groups; there was no other evidence of placental trauma. BF were better tolerated by women, provided culturable tissue, after fewer instrument passes, with greater ease and in less time. BF were associated with cost savings.\n Unlike -FP, other markers of FMH were unaltered, questioning the reliability of alpha-FP as an indicator of FMH. Compared with CA, transcervical BF caused comparable placental trauma, appeared to be similarly effective and safe and were preferred by operators and patients.", "A randomized trial involving 200 transcervical chorionic villus samples taken with three different cannulas was undertaken. In terms of karyotype recovery and ease of insertion the aluminum cannula performed best although the placental site influenced the ability to recover villi for all cannulas." ]

[ "3411737", "7735003", "11900495", "17372796", "15586837", "2685206", "2930094", "3812837", "2926945", "20466951", "2913103", "9825420", "17707898", "1999752", "17297068" ]

[ "A randomized trial of a family physician intervention for smoking cessation.", "Feasibility and effectiveness of a stages-of-change model in cigarette smoking cessation counseling.", "Efficacy of resident training in smoking cessation: a randomized, controlled trial of a program based on application of behavioral theory and practice with standardized patients.", "Randomized controlled trial of a computer-based, tailored intervention to increase smoking cessation counseling by primary care physicians.", "Results of a randomized controlled trial of intervention to implement smoking guidelines in Veterans Affairs medical centers: increased use of medications without cessation benefit.", "Training physicians about smoking cessation: a controlled trial in private practice.", "Training physicians in counseling about smoking cessation. A randomized trial of the \"Quit for Life\" program.", "Counseling medical and dental patients about cigarette smoking: the impact of nicotine gum and chart reminders.", "A randomized trial to increase smoking intervention by physicians. Doctors Helping Smokers, Round I.", "Tobacco cessation via public dental clinics: results of a randomized trial.", "Helping smokers quit: a randomized controlled trial with private practice dentists.", "Training pharmacists and pharmacy assistants in the stage-of-change model of smoking cessation: a randomised controlled trial in Scotland.", "The pediatric residency training on tobacco project: four-year resident outcome findings.", "Can residents be trained to counsel patients about quitting smoking? Results from a randomized trial.", "Effects of practitioner education, practitioner payment and reimbursement of patients' drug costs on smoking cessation in primary care: a cluster randomised trial." ]

[ "We assessed the impact of three conditions on one-year smoking cessation rates. Physicians in 70 community general practices were randomly allocated by practice to one of three groups: In the usual care group, smoking patients were to receive the care they normally would receive. In the gum only group, physicians were asked to speak to patients about smoking cessation and offer nicotine gum. In the gum plus group, physicians were trained in the experimental intervention. This intervention involved advice to stop smoking, the setting of a quit date, the offer of nicotine gum, and four follow-up visits. Smoking cessation was measured by self-report after one year and validated using saliva cotinine measures. Using a criterion of at least three months of abstinence, 8.8% of the patients of the trained physicians had stopped smoking at the one-year follow-up compared with 4.4% and 6.1% of the patients in the usual care and gum only groups, respectively.", "Counseling coupled with a stages-of-change model in cigarette smoking cessation is a useful method for physicians to help patients stop smoking. The participants were 27 physicians, randomly assigned to three groups of nine physicians each. The first group of physicians were given two lectures on the stages-of-change model on which to base their patient counseling. The second group of physicians were not exposed to the model but a reminder reading \"Ask your patients to stop smoking\" was placed in their clinic. The third group of physicians were neither exposed to the model nor given any reminder. Of the 93 smokers among the patients of the 27 physicians, 39 were in the first group, 26 in the second, and 28 in the third. A survey indicated that among the three groups there was no significant difference in demographic data, cigarette smoking history, and personal attitude toward smoking cessation counseling. At the end of six months, the first group of patients accomplished a quit smoking rate of 28.6%; of the patients still smoking 56% had decreased their daily cigarette consumption. The corresponding figures for the second group were 8.3% and 9.1%. The corresponding figures for the third group were 4.3% and 13.6%. These data show that counseling coupled with the concept of a stages-of-change model is feasible and effective to assist with cigarette smoking cessation.", "New educational programs must be developed to improve physicians' skills and effectiveness in counseling patients about smoking cessation.\n To assess the efficacy of an educational program based on behavioral theory, active learning methods, and practice with standardized patients in helping patients abstain from smoking and changing physicians' counseling practices.\n Cluster randomized, controlled trial.\n Two general internal medicine clinics in Switzerland.\n 35 residents and 251 consecutive smoking patients.\n A training program administered over two half-days, during which physicians learned to provide counseling that matched smokers' motivation to quit and practiced these skills with standardized patients acting as smokers at different stages of change. The control intervention was a didactic session on management of dyslipidemia.\n Self-reported abstinence from smoking at 1 year of follow-up, which was validated by exhaled carbon monoxide testing at one clinic; score of overall quality of counseling based on use of 14 counseling strategies; patient willingness to quit; and daily cigarette consumption.\n At 1 year of follow-up, abstinence from smoking was significantly higher in the intervention group than in the control group (13% vs. 5%; P = 0.005); this corresponded to a cluster-adjusted odds ratio of 2.8 (95% CI, 1.4 to 5.5). Residents who received the study training provided better counseling than did those who received the control training (mean score, 4.0 vs. 2.7; P = 0.002). Smokers' willingness to quit was also higher in the intervention group (94% vs. 80%; P = 0.007). A nonsignificant trend toward lower daily cigarette consumption in the intervention group was observed.\n A training program in smoking cessation administered to physicians that was based on behavioral theory and practice with standardized patients significantly increased the quality of physicians' counseling, smokers' motivation to quit, and rates of abstinence from smoking at 1 year.", "The primary care visit represents an important venue for intervening with a large population of smokers. However, physician adherence to the Smoking Cessation Clinical Guideline (5As) remains low. We evaluated the effectiveness of a computer-tailored intervention designed to increase smoking cessation counseling by primary care physicians.\n Physicians and their patients were randomized to either intervention or control conditions. In addition to brief smoking cessation training, intervention physicians and patients received a one-page report that characterized the patients' smoking habit and history and offered tailored recommendations. Physician performance of the 5As was assessed via patient exit interviews. Quit rates and smoking behaviors were assessed 6 months postintervention via patient phone interviews. Intervention effects were tested in a sample of 70 physicians and 518 of their patients. Results were analyzed via generalized and mixed linear modeling controlling for clustering.\n Intervention physicians exceeded controls on \"Assess\" (OR 5.06; 95% CI 3.22, 7.95), \"Advise\" (OR 2.79; 95% CI 1.70, 4.59), \"Assist-set goals\" (OR 4.31; 95% CI 2.59, 7.16), \"Assist-provide written materials\" (OR 5.14; 95% CI 2.60, 10.14), \"Assist-provide referral\" (OR 6.48; 95% CI 3.11, 13.49), \"Assist-discuss medication\" (OR 4.72;95% CI 2.90, 7.68), and \"Arrange\" (OR 8.14; 95% CI 3.98, 16.68), all p values being < 0.0001. Intervention patients were 1.77 (CI 0.94, 3.34,p = 0.078) times more likely than controls to be abstinent (12 versus 8%), a difference that approached, but did not reach statistical significance, and surpassed controls on number of days quit (18.4 versus 12.2, p < .05) but not on number of quit attempts.\n The use of a brief computer-tailored report improved physicians' implementation of the 5As and had a modest effect on patients' smoking behaviors 6 months postintervention.", "The AHRQ Clinical Practice Guideline for Treating Tobacco Use and Dependence recommends screening and treatment of all tobacco users. Effective methods to implement recommendations are needed because simple guideline dissemination does not necessarily result in changes in practice.\n The Guideline Implementation for Tobacco (GIFT) study tested an organizational intervention to improve Guideline implementation.\n GIFT randomized 20 Veterans Affairs medical centers to intervention or control conditions. We trained prime movers at each site to improve identification of smoking status, promote primary care interventions and increase availability of smoking cessation medications. Sites and patients were evaluated before and after intervention.\n GIFT included 20 Veterans Affairs medical centers and 5678 subjects.\n Data regarding smoking status, delivery of treatment, medication use, and smoking cessation were collected from participant surveys, medical record review, survey of site leaders, and Pharmacy Benefits Management.\n The intervention did not increase participant report of being asked about smoking status or receipt of counseling. It did increase the rate of identification of smoking status in the medical record (P = 0.0001) but did not increase the rate of counseling to stop smoking. Site level data showed no increase in the number of patients receiving smoking cessation medications or dollars spent on medications. Individual smoker data showed a significant increase in the use of medications for smoking cessation in intervention sites (odds ratio = 6.89, P < 0.0001); however, only a small minority of smokers received medication even after the intervention. There was no difference in smoking cessation rates between participants at the intervention and treatment sites.\n We conclude that improvements in smoking cessation rates are likely to require more intensive intervention in this population.", "To test the hypotheses that physicians in private practice who receive a continuing education program (entitled \"Quit for Life\") about how to counsel smokers to quit would counsel smokers more effectively and have higher rates of long-term smoking cessation among their patients.\n Randomized trial with blinded assessment of principal outcomes.\n Private practices of internal medicine and family practice.\n Forty-four physicians randomly assigned to receive training (24) or serve as controls (20) and consecutive samples of smokers visiting each physician (19.6 patients per experimental and 22.3 per control physician).\n Physicians received three hours of training about how to help smokers quit. Physicians and their office staffs were also given self-help booklets to distribute to smokers and were urged to use a system of stickers on charts as reminders to counsel smokers about quitting.\n Based on telephone interviews with patients, physicians in the experimental group were more likely to discuss smoking with patients who smoked (64% vs. 44%), spent more time counseling smokers about quitting (7.5 vs. 5.2 minutes), helped more smokers set dates to quit smoking (29% vs. 5% of smokers), gave out more self-help booklets (37% vs. 9%), and were more likely to make a follow-up appointment about quitting smoking (19% vs. 11% of those counseled) than physicians in the control group. One year later, the rates of biochemically confirmed, long-term (greater than or equal to 9 months) abstinence from smoking were similar among patients in the experimental (3.2%) and control (2.5%) groups (95% confidence interval for the 0.7% difference: -1.7 to +3.1%).\n The authors conclude that this continuing education program substantially changed the way physicians counseled smokers, but had little or no impact on rates of long-term smoking cessation among their patients. There is a need for more effective strategies to help physicians help their patients to quit smoking.", "To test whether physicians who receive a continuing education program (\"Quit for Life\") about how to counsel smokers to quit would counsel smokers more effectively and have higher rates of long-term smoking cessation among their patients who smoke.\n Randomized trial with blinded assessment of principal outcomes.\n Four health maintenance organization medical centers in northern California.\n Eighty-one internists assigned by blinded randomization to receive training (40) or serve as controls (41). Consecutive samples of smokers visiting each physician (mean, 25.6 patients per experimental and 25.2 per control physician).\n Internists received 3 hours of training about how to help smokers quit. Physicians and their office staff also were given self-help booklets to distribute free to smokers and were urged to use a system of stickers on charts to remind physicians to counsel smokers about quitting.\n On the basis of telephone interviews with patients after visiting the physician, we determined that internists who attended the Quit for Life program discussed smoking with more patients who smoked, spent more time counseling them about smoking, helped more patients set dates to quit smoking, gave out more self-help booklets, and made more follow-up appointments to discuss smoking than did internists in the control group. One year later, the rate of biochemically confirmed, long-term (greater than or equal to 9 months) abstinence from smoking was 1% higher among all patients of trained internists than among patients of controls (95% CI, -0.1% to +2.3%), and 2.2% (+0.2% to +4.3%) higher among the patients who most wanted to quit smoking.\n This continuing education program substantially changed the way physicians counseled smokers. As a result, a few more patients who wanted to quit smoking achieved long-term abstinence.", "To investigate methods for improving and expanding the counseling of smokers by physicians and dentists, we assigned 112 physicians and 50 dentists (in separate studies) to one of the following conditions: the control or advice-only group received a one-hour lecture on the consequences and management of smoking and a booklet detailing a four-step protocol for counseling patients about smoking; three other groups received, in addition, either, protocol reminder stickers placed on their patients' charts; nicotine gum made freely available to their patients; or both chart reminders and nicotine gum. Exit interviews of 1,091 medical and 647 dental patients indicated that the presence of chart reminders and/or the availability of nicotine gum increased the time spent counseling and altered the nature of the smoking cessation counseling provided by both physicians and dentists.", "Sixty-six physicians were randomized to three groups to conduct a 1-month campaign to help their patients stop smoking. The workshop group received free patient education materials and a 6-hour training workshop. The materials group received free patient education materials, and the no-assistance group received nothing. A telephone interview was completed with 89% of the 6767 eligible adult patients seen during the month of the campaign. The brief training program and patient education materials marginally increased the smoking intervention activities of volunteer physicians in private practice. Both workshop and materials physicians asked 54% of their smoking patients to stop; no-assistance physicians asked 40%. One year later, 36% of patients who had not even been asked by their doctors if they smoked reported that they had tried to stop smoking. If the physician had asked the patient if he or she smoked, the probability of a quit attempt was 47%. Patients who had been asked if they smoked were more likely to claim to have stopped (13%) than patients who had not been asked (9%). However, the proportion of patients claiming continued abstinence (range, 12% to 14%) was not related to the group of the physician.", "We sought to compare the effectiveness of a dental practitioner advice and brief counseling intervention to quit tobacco use versus usual care for patients in community health centers on tobacco cessation, reduction in tobacco use, number of quit attempts, and change in readiness to quit.\n We randomized 14 federally funded community health center dental clinics that serve diverse racial/ethnic groups in 3 states (Mississippi, New York, and Oregon) to the intervention (brief advice and assistance, including nicotine replacement therapy) or usual care group.\n We enrolled 2549 smokers. Participants in the intervention group reported significantly higher abstinence rates at the 7.5-month follow-up, for both point prevalence (F(1,12) = 6.84; P < .05) and prolonged abstinence (F(1,12) = 14.62; P < .01) than did those in the usual care group.\n The results of our study suggest the viability and effectiveness of tobacco cessation services delivered to low-income smokers via their dental health care practitioner in community health centers. Tobacco cessation services delivered in public dental clinics have the potential to improve the health and well-being of millions of Americans.", "Fifty private practitioners and their office staff members were randomly assigned to one of four groups: participants received a protocol for smoking management and a lecture on the consequences and management of smoking, or in addition, had nicotine gum freely available to patients, had stickers attached to their charts, or had gum and reminders. The percentage of patients in each group who had quit smoking a year later was 7.7, 16.3, 8.6, and 16.9, respectively, indicating a significant main effect for the gum conditions. The availability of nicotine gum also significantly increased the amount of time that patients reported they received smoking cessation counseling from the dentists and office staff.", "To evaluate a training workshop for community pharmacy personnel to improve their counselling in smoking cessation based on the stage-of-change model.\n A randomised controlled trial of community pharmacies and pharmacy customers.\n All 76 non-city community pharmacies registered in Grampian, Scotland, were invited to participate. Sixty-two pharmacies (82%) were recruited.\n All the intervention pharmacy personnel were invited to attend the training; 40 pharmacists and 54 assistants attended. A total of 492 customers who smoked (224 intervention, 268 controls) were recruited during the 12-month recruitment period (overall recruitment rate 63%).\n The perceptions of customers and pharmacy personnel of the pharmacy support and self-reported smoking cessation rates for the two groups of customers at one, four, and nine months.\n The intervention customer respondents were significantly more likely to have discussed stopping smoking with pharmacy personnel, 85% (113) compared with 62% (99) of the controls (p < 0.001). The former also rated their discussion more highly; 34% (45) of the intervention customers compared with 16% (25) of the controls rated it as \"very useful\" (p = 0.048). Assuming non-responders had lapsed, one-month point prevalence of abstinence was claimed by 30% of intervention customers and 24% of controls (p = 0.12); four months' continuous abstinence was claimed by 16% of intervention customers and 11% of controls (p = 0.094); and nine months' continuous abstinence was claimed by 12% of intervention customers and 7% of controls (p = 0.089). These trends in outcome were not affected by potential confounders (sex, age, socioeconomic status, nicotine dependence, and type of nicotine replacement product used) or adjustment for clustering.\n The intervention was associated with increased and more highly rated counselling, and a trend toward higher smoking cessation rates, indicating that community pharmacy personnel have the potential to make a significant contribution to national smoking cessation targets.", "To evaluate the efficacy of a special program for training pediatric residents to address tobacco.\n In a study conducted at the New Jersey Medical School, sixteen pediatric residency training programs in the New York/New Jersey metropolitan area were assigned randomly to either special or standard training conditions. All of the residents were invited to take part in the training. Only second- and third-year residents participated in data collection activities (baseline and follow-up tobacco surveys and objective structured clinical examinations [OSCEs]). Baseline data were collected in the spring of 2001, and follow-up data were collected annually through the spring of 2005. Special training consisted of a hybrid website/CD-ROM training program on tobacco, a seminar series, companion intervention material, and clinic mobilization. Standard training residents participated in the seminar series and utilized standard educational and self-help material.\n The percent of residents in special training, but not of those in standard training, who provided assistance for modifying environmental tobacco smoke, preventing use, and helping patients and parents stop smoking increased significantly from baseline to year 4 of training, as did the percent who felt prepared to address tobacco. Performance on the OSCEs was consistent with survey outcomes as special training residents revealed mastery of key interviewing and intervention skills.\n The special training program, with Solutions for Smoking as its centerpiece, was found to be effective for training pediatric residents to address tobacco, and it may serve as a model for pediatric residency training programs. Ways of improving the program are discussed.", "To evaluate the effectiveness of two teaching interventions to increase residents' performance of smoking cessation counseling.\n Randomized controlled factorial trial.\n Eleven residency programs, in internal medicine (six), family medicine (three), and pediatrics (two). Programs were located in three university medical centers and four university-affiliated community hospitals.\n 261 residents who saw ambulatory care patients at least one half-day per week, and 937 returning patients aged 17 to 75 years who reported having smoked five or more cigarettes in the preceding seven days. Of the 937, 843 were eligible for follow-up, and 659 (78%) were interviewed by phone at six months.\n Two interventions (tutorial and prompt) and four groups. The tutorial was a two-hour educational program in minimal-contact smoking cessation counseling for residents. The prompt was a chart-based reminder to assist physician counseling. One group of residents received the tutorial; one, the prompt; and one, both. A fourth group received no intervention.\n Six months after the intervention, physician self-reports showed that residents in the tutorial + prompt and tutorial-only groups had used more counseling techniques (1.5-1.9) than had prompt-only or control residents (0.9). Residents in all three intervention groups advised more patients to quit smoking (76-79%) than did control group residents (69%). The tutorial had more effect on counseling practices than did the prompt. Physician confidence, perceived preparedness, and perceived success followed similar patterns. Exit interviews with 937 patients corroborated physician self-reports of counseling practices. Six months later, self-reported and biochemically verified patient quitting rates for residents in the three intervention groups (self-reported: 5.3-8.2%; biochemically verified: 3.4-5.7%) were higher than those for residents in the control group (self-reported: 5.2%; biochemically verified: 1.7%), though the differences were not statistically significant.\n A simple and feasible educational intervention can increase residents' smoking cessation counseling.", "To evaluate new strategies to enhance the promotion of smoking cessation in general practice.\n Cluster randomised trial, 2x2 factorial design.\n 82 medical practices in Germany, including 94 general practitioners.\n 577 patients who smoked at least 10 cigarettes per day (irrespective of their intention to stop smoking) and were aged 36-75 years.\n Provision of a 2-h physician group training in smoking cessation methods and direct physician payments for every participant not smoking 12 months after recruitment (TI, training+incentive); provision of the same training and direct participant reimbursements for pharmacy costs associated with nicotine replacement therapy or bupropion treatment (TM, training+medication).\n Self-reported smoking abstinence obtained at 12 months follow-up and validated by serum cotinine.\n In intention-to-treat analysis, smoking abstinence at 12 months follow-up was 3% (2/74), 3% (5/144), 12% (17/140) and 15% (32/219) in the usual care, and interventions TI, TM and TI+TM, respectively. Applying a mixed logistic regression model, no effect was identified for intervention TI (odds ratio (OR) 1.26, 95% confidence interval (CI) 0.65 to 2.43), but intervention TM strongly increased the odds of cessation (OR 4.77, 95% CI 2.03 to 11.22).\n Providing cost-free effective drugs to patients along with improved training opportunities for general practitioners could be an effective measure to achieve successful promotion of smoking cessation in general practice." ]

[ "16087692", "9672959", "10890292", "1409487", "19736331", "14993087", "10691755", "12406481", "1302446", "12580689", "19299670", "9242036", "2785610", "14654501", "9584038", "11304094", "18478333", "19103639", "11875146" ]

[ "The European Smoking prevention Framework Approach (ESFA): effects after 24 and 30 months.", "One-year outcomes of Project Towards No Drug Abuse.", "Preventing substance use among Native American youth: three-year results.", "Results from a statewide approach to adolescent tobacco use prevention.", "Results of a type 2 translational research trial to prevent adolescent drug use and delinquency: a test of Communities That Care.", "Effects of an advocacy intervention to reduce smoking among teenagers.", "A randomised controlled trial of a community intervention to prevent adolescent tobacco use.", "Tobacco and alcohol use-prevention program for Hispanic migrant adolescents.", "Drug prevention in a community setting: a longitudinal study of the relative effectiveness of a three-year primary prevention program in boys & girls clubs across the nation.", "A randomized controlled trial of the middle and junior high school D.A.R.E. and D.A.R.E. Plus programs.", "Preventing tobacco use among young people in India: Project MYTRI.", "The impact of heart health promotion on coronary heart disease lifestyle risk factors in schoolchildren: lessons learnt from a community-based project.", "A multicommunity trial for primary prevention of adolescent drug abuse. Effects on drug use prevalence.", "Evaluation of a Health Promoting Schools program to reduce smoking in Australian secondary schools.", "Fifteen-year follow-up of smoking prevention effects in the North Karelia youth project.", "The effect of a community action intervention on adolescent smoking rates in rural australian towns: the CART project. Cancer Action in Rural Towns.", "The impact on tobacco use of branded youth anti-tobacco activities and family communications about tobacco.", "The relationship between local clean indoor air policies and smoking behaviours in Minnesota youth.", "A pediatric, practice-based, randomized trial of drinking and smoking prevention and bicycle helmet, gun, and seatbelt safety promotion." ]

[ "The European Smoking Prevention Framework Approach (ESFA) study in six countries tested the effects of a comprehensive smoking prevention approach after 24 (T3; N = 10,751) and 30 months (T4; N = 9,282). The programme targeted four levels, i.e. adolescents in schools, school policies, parents and the community. In Portugal, 12.4% of the T1 non-smokers in the control group had started smoking at T4 compared to 7.9% of the experimental group. Smoking onset in the experimental group was thus 36% lower. In Finland, 32.4% of the T1 non-smokers started smoking compared to 27.6% of the experimental group, implying a 15% lower onset in the experimental group. In Spain, 33.0% of the T1 non-smokers in the control group had started smoking, compared to 29.1% of the experimental group, implying a 12% lower onset. In The Netherlands, the ESFA programme was effective for non-native adolescents with 11.4% new weekly smokers compared to 19.9% in the control group. An opposite effect was found in native Dutch adolescents with 19.0% new weekly smokers in the comparison group compared to 24.0% new smokers in the experimental group. Future programmes should use more standardized ways to assess process evaluations and should assess which elements are responsible for behavioral effects.", "This paper presents the 1-year outcomes evaluation of Project Towards No Drug Abuse (Project TND), a large-scale indicated drug abuse prevention program in southern California applied to continuation high school youth, who are at high risk for drug abuse.\n The efficacy of nine-lesson health motivation--social skills--decision-making curriculum was evaluated in a three-condition experimental design. Twenty-one schools were randomly assigned by block to one of three conditions--standard care (control), classroom program, and classroom program plus a semester-long school-as-community component. A pretest was followed by a 3-week-long drug abuse prevention program and then a posttest at 14 continuation high schools. The 7 standard care schools received only the pretest followed by the posttest (same time duration). Subjects were followed up 1 year later.\n Changes in use of cigarettes, alcohol, marijuana, and hard drugs were assessed in a pretest-1-year follow-up time interval. The follow-up rate was 67% (analysis n = 1,074). Indicated preventive effects were found on alcohol and hard drug use. No differences were found across the two program conditions.\n Project TND is the first program to demonstrate 1-year self-reported behavioral effects on alcohol use and hard drug use among older, high-risk youth by using a school-based, limited-session model.", "This study developed and tested skills- and community-based approaches to prevent substance abuse among Native American youth. After completing pretest measurements, 1,396 third- through fifth-grade Native American students from 27 elementary schools in five states were divided randomly by school into two intervention arms and one control arm. Following intervention delivery, youths in all arms completed posttest measurements and three annual follow-up measurements. Youths in schools assigned to the intervention arms learned cognitive and behavioral skills for substance abuse prevention. One intervention arm additionally engaged local community residents in efforts to prevent substance use among Native American youth. Outcome assessment batteries measured youths' reported use of smoked and smokeless tobacco, alcohol, and marijuana. Over the course of the 3.5-year study, increased rates of tobacco, alcohol, and marijuana use were reported by youths across the three arms of the study. Though cigarette use was unaffected by intervention, follow up rates of smokeless tobacco, alcohol, and marijuana use were lower for youths who received skills intervention than for youths in the control arm. Community intervention components appeared to exert no added beneficial influence on youths' substance use, beyond the impact of skills intervention components alone. Finally, gender differences were apparent across substances, measurements, and study arms, with girls smoking more cigarettes and boys using more smokeless tobacco, alcohol, and marijuana.", "The 1985 Minnesota Legislature established guidelines for school-based tobacco-use prevention programming and provided financial incentives to school districts to encourage them to adopt a broad range of preventive measures. The Minnesota-Wisconsin Adolescent Tobacco-Use Research Project was funded by the National Cancer Institute in 1986 to evaluate the Minnesota initiative through two parallel studies.\n The Four Group Comparison Study was a prospective study of 48 school \"units\" which were randomly assigned to one of four conditions in 1987. Baseline observations were taken in the sixth grade in 1987, interventions were delivered in the seventh grade, and follow-up observations were taken in the seventh, eighth, and ninth grades. The Four Group Comparison Study was designed to evaluate the three middle-school interventions that were most widely adopted by Minnesota school districts as a result of the 1985 legislation. The Two State Comparison Study was a serial cross-sectional study of representative districts in Minnesota and Wisconsin. Annual surveys of ninth graders were conducted from 1986-1990. The Two State Comparison Study was designed to determine whether tobacco-use patterns changed in Minnesota relative to Wisconsin following the Minnesota legislation.\n The prospective study indicated that none of the interventions was more effective in reducing adolescent tobacco use compared with a randomized control group. The serial cross-sectional study revealed that there was a modest net decline in Minnesota relative to Wisconsin from 1986 to 1990, but that it was within the range of chance variation.\n Taken together, these results indicate that this legislative initiative was insufficient to reduce adolescent tobacco use statewide during the 5-year study period. Together with results from other recent studies, they suggest that even more intensive efforts may be required to effect widespread reductions in adolescent tobacco use.", "To test whether the Communities That Care (CTC) prevention system reduces adolescent alcohol, tobacco, and other drug use and delinquent behavior communitywide.\n The Community Youth Development Study is the first randomized trial of CTC.\n In 2003, 24 small towns in 7 states, matched within state, were randomly assigned to control or CTC conditions.\n A panel of 4407 fifth-grade students was surveyed annually through eighth grade. Intervention A coalition of community stakeholders received training and technical assistance to install the CTC prevention system. They used epidemiological data to identify elevated risk factors and depressed protective factors in the community, and chose and implemented tested programs to address their community's specific profile from a menu of effective programs for families, schools, and youths aged 10 to 14 years.\n Incidence and prevalence of alcohol, tobacco, and other drug use and delinquent behavior by spring of grade 8.\n The incidences of alcohol, cigarette and smokeless tobacco initiation, and delinquent behavior were significantly lower in CTC than in control communities for students in grades 5 through 8. In grade 8, the prevalences of alcohol and smokeless tobacco use in the last 30 days, binge drinking in the last 2 weeks, and the number of different delinquent behaviors committed in the last year were significantly lower for students in CTC communities.\n Using the CTC system to reduce health-risking behaviors in adolescents can significantly reduce these behaviors communitywide.", "To test whether high school students' participation in advocacy activities related to the advertising, availability, and use of tobacco in their communities would prevent or reduce their own tobacco use.\n Ten continuation high schools in northern California, randomly assigned to a semester-long program in which students either carried out advocacy activities to counter environmental-level smoking influences in their communities (treatment) or learned about drug and alcohol abuse prevention (control).\n Eleventh and 12th grade high school students; 5 (advocacy) treatment and 5 control schools over 4 semesters from 2000 through 2002.\n Self-reported smoking defined as nonsmokers (those who had never smoked tobacco or those who were former smokers), light smokers (those who smoked <1 pack per week), or regular smokers (those who smoked >or=1 pack per week), and confirmed by carbon monoxide level readings. The following 3 constructs related to social cognitive theory- perceived incentive value, perceived self-efficacy, and outcome expectancies-were assessed.\n There was a significant net change from baseline to the end of the semester (after the intervention) between treatment and control schools for students who were regular smokers, but not for students who were nonsmokers or light smokers. Regular smoking decreased 3.8% in treatment schools and increased 1.5% in control schools (P<.001). Regular smoking continued to decrease at 6 months after the intervention in treatment schools, with a total change in prevalence from 25.1% to 20.3%. Involvement in community-advocacy activities and the 3 social constructs-perceived incentive value, perceived self-efficacy, and outcome expectancies-also showed significant net changes between treatment and control schools (all P values <.01).\n Student engagement in community-advocacy activities that addressed environmental influences of cigarette smoking resulted in significant decreases in regular smoking.", "Experimental evaluation of comprehensive community wide programme to prevent adolescent tobacco use.\n Eight pairs of small Oregon communities (population 1700 to 13 500) were randomly assigned to receive a school based prevention programme or the school based programme plus a community programme. Effects were assessed through five annual surveys (time 1-5) of seventh and ninth grade (ages 12-15 years) students.\n The community programme included: (a) media advocacy, (b) youth anti-tobacco activities, (c) family communications about tobacco use, and (d) reduction of youth access to tobacco.\n The prevalence of self reported smoking and smokeless tobacco use in the week before assessment.\n The community programme had significant effects on the prevalence of weekly cigarette use at times 2 and 5 and the effect approached significance at time 4. An effect on the slope of prevalence across time points was evident only when time 2 data points were eliminated from the analysis. The intervention affected the prevalence of smokeless tobacco among grade 9 boys at time 2. There were also significant effects on the slope of alcohol use among ninth graders and the quadratic slope of marijuana for all students.\n The results suggest that comprehensive community wide interventions can improve on the preventive effect of school based tobacco prevention programmes and that effective tobacco prevention may prevent other substance use.", "Evaluate a community-based tobacco/alcohol use-prevention program group compared with an attention-control condition (first aid/home safety) group.\n A total of 660 adolescents and 1 adult caregiver for each were recruited through the Migrant Education Program to participate in an 8-week intervention. Random assignment to the two groups occurred in 22 schools. Seventy 8-week intervention groups (37 tobacco/alcohol and 33 attention-control) were conducted. Assessments occurred at baseline, immediate post-intervention, and 1- and 2-year follow-ups. Susceptibility to smoking and alcohol as well as smoking and drinking over the past 30 days were the primary outcomes of interest.\n Following intervention, no between-group differences in smoking or drinking were significant. Thirty-day smoking started and remained at very low levels, with the highest group prevalence at any measurement period being 4.7% and the lowest 2.5%. Those considered susceptible to smoking dropped by nearly 40% in the attention-control group and by 50% in the intervention group from baseline to the final follow-up. (The overall reduction from post-test to final follow-up was statistically significant.) Less-acculturated children were less likely to report drinking in the past 30 days.\n The current intervention was not demonstrated to be effective in preventing cigarette or alcohol consumption. This perhaps is due to very low baseline levels of smoking and drinking in the migrant youth participants.", "Tested the effectiveness of a youth drug prevention program in a community setting. Boys & Girls Clubs of America's Stay SMART program, adapted from a school-based personal and social competence drug prevention program, was offered, with and without a 2-year booster program, to 13-year-old members of Boys & Girls Clubs. Over 27 months, (a) 5 Boys & Girls Clubs offered the Stay SMART program, (b) 5 Boys & Girls Clubs offered the Stay SMART program with the booster programs, and (c) 4 Boys & Girls Clubs served as a control group. The Stay SMART program alone and the Stay SMART program with the booster programs showed effects for marijuana-related behavior, cigarette-related behavior, alcohol-related behavior, overall drug-related behavior, and knowledge concerning drug use. The Stay SMART program with the booster programs produced additional effects for alcohol attitudes and marijuana attitudes after each year of booster programs. Results suggest that a school-based personal and social competence program can be adapted effectively to a community setting and that booster programs might enhance program effects. Implications for alternative community models of prevention are discussed.", "To evaluate the effect of the middle and junior high school Drug Abuse Resistance Education (D.A.R.E.) and D.A.R.E. Plus programs on drug use and violence.\n Randomized controlled trial of 24 schools, with 3 conditions: D.A.R.E. only, D.A.R.E. Plus, and delayed program control.\n Schools and neighborhoods, primarily in Minneapolis-St Paul.\n All seventh-grade students in 24 schools in the academic year 1999-2000 (N = 6237 at baseline, 67.3% were white, and there was 84.0% retention at final follow-up).\n The middle and junior high school D.A.R.E. curriculum in the 16 schools that received D.A.R.E. only and D.A.R.E. Plus. In the 8 schoolts that received D.A.R.E. Plus, additional components included a peer-led parental involvement classroom program called \"On the VERGE,\" youth-led extracurricular activities, community adult action teams, and postcard mailings to parents. The interventions were implemented during 2 school years, when the cohort was in the seventh and eighth grades.\n Self-reported tobacco, alcohol, and marijuana use; multidrug use; violence; and victimization, assessed at the beginning and end of seventh grade and at the end of eighth grade. Growth curve analytic methods were used to assess changes over time by condition.\n There were no significant differences between D.A.R.E. only and the controls; significant differences among boys between D.A.R.E. Plus and controls for tobacco, alcohol, and multidrug use and victimization; significant differences among boys between D.A.R.E. Plus and D.A.R.E. only in tobacco use and violence; and no significant behavioral differences among girls.\n D.A.R.E. Plus significantly enhanced the effectiveness of the D.A.R.E. curriculum among boys and was more effective than the delayed program controls, underscoring the potential for multiyear, multicomponent prevention programs and demonstrating sex differences in response to intervention programs.", "We assessed the effectiveness of a 2-year multicomponent, school-based intervention designed to reduce tobacco use rates among adolescents in an urban area of India.\n Students from 32 schools in Delhi and Chennai, India, were recruited and randomly assigned to an intervention or control group. Baseline, intermediate, and outcome data were collected from 2 cohorts of 6th- and 8th-grade students in 2004; 14,063 students took part in the study and completed a survey in 2004, 2005, or 2006. The intervention consisted of behavioral classroom curricula, school posters, a parental involvement component, and peer-led activism. The main outcome measures were self-reported use of cigarettes, bidis (small hand-rolled, often flavored, cigarettes), and chewing tobacco and future intentions to smoke or use chewing tobacco.\n Findings showed that students in the intervention group were significantly less likely than were students in the control group to exhibit increases in cigarette smoking or bidi smoking over the 2-year study period. They were also less likely to intend to smoke or chew tobacco in the future.\n School-based programs similar to the intervention examined here should be considered as part of a multistrategy approach to reducing tobacco use among young people in India.", "A community health promotion project called Action Heart was undertaken in two electoral wards in Rotherham to try to change lifestyles of people. Schools were included within the project. Coronary heart disease lifestyle risk factors were measured at baseline and after a three year period in the intervention area and a similar control area. Lifestyle factors in schoolchildren were measured separately from adults using a different instrument. The post intervention survey of adults and economic evaluation demonstrated that Action Heart had achieved cost-effective estimated health gains. In the schoolchildren however, a mixture of positive and negative risk factor changes in both areas was demonstrated. Significant changes in lifestyle risk factors in schoolchildren were not elicited using this approach. The possible reasons for the lack of impact on lifestyle risk factors in schoolchildren are examined and the implications for further work explored.", "The entire early adolescent population of the 15 communities that constitute the Kansas City (Kansas and Missouri) metropolitan area has participated in a community-based program for prevention of drug abuse since September 1984. The Kansas City area is the first of two major metropolitan sites being evaluated in the Midwestern Prevention Project, a longitudinal trial for primary prevention of cigarette, alcohol, and marijuana use in adolescents. The project includes mass media programming, a school-based educational program for youths, parent education and organization, community organization, and health policy components that are introduced sequentially into communities during a 6-year period. Effects of the program are determined through annual assessments of adolescent drug use in schools that are assigned to immediate intervention or delayed intervention control conditions. In the first 2 years of the project, 22,500 sixth- and seventh-grade adolescents received the school-based educational program component, with parental involvement in homework and mass media coverage. Analyses of 42 schools indicate that the prevalence rates of use for all three drugs are significantly lower at 1-year follow-up in the intervention condition relative to the delayed intervention condition, with or without controlling for race, grade, socioeconomic status, and urbanicity (17% vs 24% for cigarette smoking, 11% vs 16% for alcohol use, and 7% vs 10% for marijuana use in the last month), and the net increase in drug use prevalence among intervention schools is half that of delayed intervention schools.", "This randomized controlled trial evaluated the effectiveness of a multicomponent Health Promoting Schools (HPS) intervention program in improving self-reported smoking outcomes among a cohort of adolescents in 22 public secondary schools in the Hunter Region of New South Wales, Australia. Pre-test surveys were completed by students in the first 2 years of secondary school, with a 2-year post-test survey. Multivariate analyses examined intervention effect for the main outcome, post-test smoking behavior, controlling for pre-test smoking status, school and other confounders. The sample comprised the cohort of 1852 students who completed both surveys. The results demonstrated that the HPS program failed to improve smoking behavior over the 2 years (equal increase of 10% in both groups). The program was successful in improving smoking knowledge, but not attitudes, in intervention versus control group (P < 0.001). Independent predictors of post-test smoking included: pre-test smoking [odds ratio (OR) = 5.44; 95% confidence interval (CI) = 3.20-9.28], being female (OR = 0.55; CI = 0.35-0.87), having more close friends who smoked (OR = 1.42; CI = 1.33-1.52), peer group having no clear opinion about smoking (OR = 3.23; CI = 1.27-8.27), having more positive and less negative attitudes towards smoking, and being less involved in school activities. We discuss methodological issues in multicomponent community-based interventions, and highlight the strengths and limitations of this study.", "This study evaluated the long-term effects of a school- and community-based smoking prevention program in Finland.\n Four intervention schools from North Karelia and two control schools from another province were chosen for the evaluation. Students who received the intervention were taught to resist social pressures to smoke. The program began in 1978 with seventh-grade students and ran through 1980, with a 15-year follow-up. In North Karelia, a community-based smoking cessation program for adults was also carried out.\n Mean lifetime cigarette consumption was 22% lower among program subjects than among control subjects. Smoking and prevalence were lower up to the age of 21.\n Long-term smoking prevention effects can be achieved if a school-based program using a social influence model is combined with community and mass media interventions.", "This paper describes one outcome of a randomized controlled trial of community action for cancer prevention, Cancer Action in Rural Towns. The aims are to [1] explore the effectiveness of community action in decreasing adolescent smoking in rural Australian towns; and [2] describe the relationship between adolescent smoking rates and demographic variables.\n In 1992, 20 rural Australian towns were selected. Community action involved formation of community committees and utilization of access-point networks to initiate and maintain intervention strategies. Cross-sectional surveys of smoking behaviors for all Year 9 and Year 10 students (13-16 years) in each town were conducted pre- and posttest. The main outcome measure was self-reported smoking in the past 4 weeks. SUDAAN software was used to look at differences between treatment.\n The results showed strong secular trends toward increased adolescent smoking, regardless of treatment group, particularly for females. There was no significant intervention effect.\n Increasing adolescent smoking rates found in this and other studies highlight that the definitive strategy to stem the adolescent smoking epidemic has not been found. Hope may remain for recent legislative strategies, but rigorous evaluation is essential, and compliance with legislation should be carefully monitored.\n Copyright 2001 American Health Foundation and Academic Press.", "In a randomized controlled trial, we evaluated the effect on tobacco use onset among middle school students of Family Communications (FC) activities designed to mobilize parental influences against tobacco use and Youth Anti-tobacco Activities (YAT) designed to market anti-tobacco norms to adolescents. We conducted a simple, two-condition experimental design in which 40 middle schools, with a prevalence of tobacco use at or above the Oregon median, received, by random assignment, either the intervention or no intervention. State, county, and local prevention coordinators around Oregon served as liaisons to schools. To generate interest, staff made presentations to these groups and distributed marketing packets at several conferences. Dependent variables were indices of smoking prevalence and use of smokeless tobacco (ST) in the prior month. Additionally, we created an intervention manual so that other communities could replicate this study. The findings suggest that efforts to influence parents to discourage their children's tobacco use and efforts to market an anti-tobacco perspective to teens are effective in preventing smoking. The impact of YAT is consistent with experimental and nonexperimental evaluations of media campaigns to influence young people not to smoke.", "While clean indoor air (CIA) policies are intended to reduce exposure to second-hand smoke in the workplace, restrictions in public workplaces have the potential to discourage youth smoking. There is growing evidence from cross-sectional and ecological studies, but limited evidence from longitudinal studies that this is so.\n To evaluate the association between local CIA policies and smoking behaviours among Minnesota youth over time. Design, setting and\n A cohort of 4233 Minnesota youths, ages 11 to 16 at baseline, was interviewed via telephone for 6 years (2000-2006). Individual, family and community level variables were collected from participants every 6 months. A generalised estimating equation (GEE) logistic regression was used to assess the relationship between CIA policies and past-month smoking in youth over time. The analysis was controlled for potential confounders at individual and community levels.\n There was not significant association between CIA policies and youth smoking behaviours in the multivariate analyses. At the individual level, parental smoking significantly increased the odds of smoking nearly 40% and close friend smoking increased the odds of past-month smoking by nearly 100% for each close friend. Banning smoking in the home was significantly associated with a 12% reduction in the odds of past-month smoking.\n After accounting for other community and individual level factors known to be associated with youth smoking, there was no significant association between CIA policies and past-month smoking for youth over time.", "To prevent early adolescent health risk behaviors and to maintain or improve safety behaviors, we compared the effects of 2 interventions, delivered through pediatric primary care practices. The interventions, based on an office systems' approach, sought to prevent early drinking and smoking or to influence bicycle helmet use, gun storage, and seatbelt safety for children who were followed from fifth/sixth grades through eighth/ninth grades.\n Settings and Participants. Twelve pediatric practices in New England were paired according to practice size and assigned randomly within pairs to deliver the multicomponent interventions, which built on pediatric primary care clinicians performing as counselors and role models during health supervision visits and other office encounters.\n One intervention arm focused on alcohol and tobacco use. The other intervention arm focused on gun safety, bicycle helmet, and seatbelt use. Office systems provided infrastructure that supported the clinician's role. Clinician messages encouraged family communication and rule setting about the issues of the middle school years. The intervention was initiated during a health supervision visit and continued for 36 months. Both child and parent received quarterly newsletters to reinforce the clinician messages.\n The primary outcomes were ever drinking alcohol, ever smoking, ever using smokeless tobacco, using a bicycle helmet in the previous year, using a seatbelt in the previous 30 days, and guns in the child's home in locked storage.\n The pediatric practices recruited 85% (N = 3525) of the practices' fifth/sixth grade children and their responding parents. We obtained 36 months' follow-up data on 2183 child-parent pairs. Chart audit verified that the intervention was implemented. Additional data from interviews and surveys showed that parents, children, and pediatric clinicians found the intervention useful. Despite this, comparisons between the 2 study arms show no significant intervention effects in the prevention of alcohol and tobacco use or gun storage or seatbelt safety. There was a negative effect in the alcohol arm. Only bicycle helmet use showed a positive outcome.\n With rigorous evaluation, 2 office interventions failed to produce desired outcomes. Coordinated multiple settings for prevention interventions are probably necessary." ]

[ "2657424", "1739446", "4949207", "1913367", "7964712", "5039326", "9347598", "1623444" ]

[ "Intrathecal baclofen for severe spinal spasticity.", "Intrathecal baclofen. Effects on nocturnal leg muscle spasticity.", "An objective assessment of a gamma aminobutyric acid derivative in the control of spasticity.", "Modulation of locomotor patterns and spasticity with clonidine in spinal cord injured patients.", "A comparison of clonidine, cyproheptadine and baclofen in spastic spinal cord injured patients.", "A double blind, cross-over trial of Valium in the treatment of spasticity.", "Gabapentin for the treatment of spasticity in patients with spinal cord injury.", "Intrathecal baclofen for intractable spinal spasticity--a double-blind cross-over comparison with placebo in 6 patients." ]

[ "We studied the effect of the intrathecal infusion of baclofen, an agonist of gamma-aminobutyric acid, on abnormal muscle tone and spasms associated with spinal spasticity, in a randomized double-blind crossover study. Twenty patients with spinal spasticity caused by multiple sclerosis or spinal-cord injury who had had no response to treatment with oral baclofen received an intrathecal infusion of baclofen or saline for three days. The infusions were administered by means of a programmable pump implanted in the lumbar subarachnoid space. Muscle tone decreased in all 20 patients (mean [+/- SD] Ashworth score for rigidity, from 4.0 +/- 1.0 to 1.2 +/- 0.4; P less than 0.0001), and spasms were decreased in 18 of the 19 patients who had spasms (mean [+/- SD] score for spasm frequency, from 3.3 +/- 1.2 to 0.4 +/- 0.8; P less than 0.0005). Tests for motor function, neurologic examination, and assessments by the patients correctly indicated when baclofen was being infused in all cases. All patients were then entered in an open long-term trial of continuous infusion of intrathecal baclofen. During a mean follow-up period of 19.2 months (range, 10 to 33), muscle tone has been maintained within the normal range (mean Ashworth score, 1.0 +/- 0.1) and spasms have been reduced to a level that does not interfere with activities of daily living (mean spasm score, 0.3 +/- 0.6). No drowsiness or confusion occurred, one pump failed, and two catheters became dislodged and had to be replaced. No infections were observed. Our observations suggest that intrathecal baclofen is an effective long-term treatment for spinal spasticity that has not responded to oral baclofen.", "Electromyographic activity was recorded from tibialis anterior during nocturnal polysomnography in six patients with severe spasticity of spinal origin. The patients had a baclofen reservoir system implanted subcutaneously into their lumbar subarachnoid space and were studied for two nights in a double-blind, placebo controlled, crossover design. Tibialis anterior electromyographic activity per hour of sleep was reduced on the night of baclofen infusion. In particular, less electromyographic activity occurred after arousal from sleep.", "nan", "This double blind cross-over study, involving 9 chronic spinal cord injured (SCI) patients (6 paraplegic and 3 paretic), was a first attempt to investigate the effects of the noradrenergic agonist, clonidine, on the modulation of the locomotor pattern and spasticity in patients with spinal cord lesions. Electromyographic (EMG), footswitch and video recordings were made as the patients walked on a treadmill with the support of an overhead harness if needed. Overground locomotion was also assessed in the paretic patients. All 3 spastic paretic patients had kinematic deviations and abnormal EMG recruitment profiles during the premedication or placebo sessions. With clonidine therapy one patient demonstrated a marked improvement in locomotor function. This patient progressed from non-ambulation to limited independent ambulation as the extent of coactivation in antagonist muscles decreased. The other 2 paretics who presented limited spasticity showed minimal changes while on clonidine. In the paraplegic patients, clonidine did not elicit locomotor activity, although there were marked reductions in stretch reactions and clonus during assisted locomotion. They remained incapable of locomotion, either during the control period or during the clonidine therapy. These results indicate that clonidine may be a potentially useful medication for both locomotion and certain manifestations of spasticity in SCI patients but further investigation is warranted.", "In twenty-five SCI subjects, antispasticity effects of three putative antispasticity agents [clonidine (an alpha-2 noradrenergic agonist), cyproheptadine (a 5-HT2 antagonist) and baclofen (a GABA-B agonist)] were tested in terms of changes in leg tone as graded by the Ashworth scale (AS), in terms of the vibratory inhibition of the H-reflex (VII) and in terms of the ability of the knee to swing passively in the pendulum test as quantified by video motion analysis. When compared to the no drug period, all three drug treatments showed an antispasticity effect on the AS, the VII and the amplitude of the first swing and the relaxation index of the pendulum test, p. < 0001. Surprisingly, cyproheptadine and baclofen produced a greater reduction in the VII than clonidine, p. < 01. The amplitude of the first swing in the pendulum test correlated well with the AS, r = .88, and the antispasticity effects of the drugs produced improvements in both measures, a reduced AS and increased amplitude of knee swing in the pendulum test. Therefore, video motion analysis of the pendulum test is as valid a measure of spasticity as the Ashworth scale and is not limited by subjectivity of the examiner.", "nan", "Our serendipitous observations suggested that some patients with spasticity appeared to have improved following the administration of the anticonvulsant drug gabapentin. As some patients with spasticity are either refractory to or intolerant of established medical treatments, we conducted this study to investigate the effect of gabapentin on spasticity in patients with spinal cord injury. Twenty-five patients with spinal cord injury and spasticity received oral gabapentin (2400 mg over 48 h) in a randomized, double blind, placebo-controlled crossover study. We assessed responses by measuring the Ashworth spasticity scale, muscle stretch reflexes, presence of clonus and reflex response to noxious stimuli. Patient ratings were obtained using a Likert Scale. Administration of gabapentin, but not placebo, was associated with an 11% reduction in spasticity as measured by the Ashworth Scale (P = 0.04) and by a 20% reduction in the Likert Scale (P = 0.0013). Significant changes were not obtained for the other measures. The data obtained suggest that gabapentin may be useful in the management of spasticity associated with spinal cord injury.", "A group of six subjects with intractable spinal spasticity completed a double-blind cross-over paradigm in which they received two intrathecal bolus injections of baclofen solution five hours apart on two different days and two intrathecal bolus injections of placebo saline five hours apart on two other days. Each subject was repeatedly tested with a battery of clinical and physiological tests. In contrast to the placebo injections, the group responded to the baclofen injections with subjective and objective, clinically significant improvement in parameters of spasticity in their lower limbs, including muscle tone, frequency of spasms, hyperreflexia and passive range of joint motion. Furthermore, this improvement was maintained following thirty consecutive days of intrathecal bolus injections of baclofen at a fixed dose." ]

[ "15981758", "15155403", "15817865", "20980648" ]

[ "Home-based therapy with ready-to-use therapeutic food is of benefit to malnourished, HIV-infected Malawian children.", "Home based therapy for severe malnutrition with ready-to-use food.", "Comparison of home-based therapy with ready-to-use therapeutic food with standard therapy in the treatment of malnourished Malawian children: a controlled, clinical effectiveness trial.", "A ready-to-use therapeutic food containing 10% milk is less effective than one with 25% milk in the treatment of severely malnourished children." ]

[ "To determine if home-based nutritional therapy will benefit a significant fraction of malnourished, HIV-infected Malawian children, and to determine if ready-to-use therapeutic food (RUTF) is more effective in home-based nutritional therapy than traditional foods.\n 93 HIV-positive children >1 y old discharged from the nutrition unit in Blantyre, Malawi were systematically allocated to one of three dietary regimens: RUTF, RUTF supplement or blended maize/soy flour. RUTF and maize/soy flour provided 730 kJ x kg(-1) x d(-1), while the RUTF supplement provided a fixed amount of energy, 2100 kJ/d. These children did not receive antiretroviral chemotherapy. Children were followed fortnightly. Children completed the study when they reached 100% weight-for-height, relapsed or died. Outcomes were compared using regression modeling to account for differences in the severity of malnutrition between the dietary groups.\n 52/93 (56%) of all children reached 100% weight-for-height. Regression modeling found that the children receiving RUTF gained weight more rapidly and were more likely to reach 100% weight-for-height than the other two dietary groups (p < 0.05).\n More than half of malnourished, HIV-infected children not receiving antiretroviral chemotherapy benefit from home-based nutritional rehabilitation. Home-based therapy RUTF is associated with more rapid weight gain and a higher likelihood of reaching 100% weight-for-height.", "The standard treatment of severe malnutrition in Malawi often utilises prolonged inpatient care, and after discharge results in high rates of relapse.\n To test the hypothesis that the recovery rate, defined as catch-up growth such that weight-for-height z score >0 (WHZ, based on initial height) for ready-to-use food (RTUF) is greater than two other home based dietary regimens in the treatment of malnutrition.\n HIV negative children >1 year old discharged from the nutrition unit in Blantyre, Malawi were systematically allocated to one of three dietary regimens: RTUF, RTUF supplement, or blended maize/soy flour. RTUF and maize/soy flour provided 730 kJ/kg/day, while the RTUF supplement provided a fixed amount of energy, 2100 kJ/day. Children were followed fortnightly. Children completed the study when they reached WHZ >0, relapsed, or died. Outcomes were compared using a time-event model.\n A total of 282 children were enrolled. Children receiving RTUF were more likely to reach WHZ >0 than those receiving RTUF supplement or maize/soy flour (95% v 78%, RR 1.2, 95% CI 1.1 to 1.3). The average weight gain was 5.2 g/kg/day in the RTUF group compared to 3.1 g/kg/day for the maize/soy and RTUF supplement groups. Six months later, 96% of all children that reached WHZ >0 were not wasted.\n Home based therapy of malnutrition with RTUF was successful; further operational work is needed to implement this promising therapy.", "Childhood malnutrition is common in Malawi, and the standard treatment, which follows international guidelines, results in poor recovery rates. Higher recovery rates have been seen in pilot studies of home-based therapy with ready-to-use therapeutic food (RUTF).\n The objective was to compare the recovery rates among children with moderate and severe wasting, kwashiorkor, or both receiving either home-based therapy with RUTF or standard inpatient therapy.\n A controlled, comparative, clinical effectiveness trial was conducted in southern Malawi with 1178 malnourished children. Children were systematically allocated to either standard therapy (186 children) or home-based therapy with RUTF (992 children) according to a stepped wedge design to control for bias introduced by the season of the year. Recovery, defined as reaching a weight-for-height z score > -2, and relapse or death were the primary outcomes. The rate of weight gain and the prevalence of fever, cough, and diarrhea were the secondary outcomes.\n Children who received home-based therapy with RUTF were more likely to achieve a weight-for-height z score > -2 than were those who received standard therapy (79% compared with 46%; P < 0.001) and were less likely to relapse or die (8.7% compared with 16.7%; P < 0.001). Children who received home-based therapy with RUTF had greater rates of weight gain (3.5 compared with 2.0 g . kg(-1) . d(-1); difference: 1.5; 95% CI: 1.0, 2.0 g . kg(-1) . d(-1)) and a lower prevalence of fever, cough, and diarrhea than did children who received standard therapy.\n Home-based therapy with RUTF is associated with better outcomes for childhood malnutrition than is standard therapy.", "Standard therapy for severe acute malnutrition (SAM) is home-based therapy with ready-to-use therapeutic food (RUTF) containing 25% milk. In an effort to lower the cost of RUTF and increase availability, some have suggested that a portion of milk be replaced with soy. This trial was designed to determine whether treating children with SAM with 10% milk RUTF containing soy would result in a similar recovery rate compared with the 25% milk RUTF. This was a randomized, double-blind, controlled, clinical, quasi-effectiveness trial of isoenergetic amounts of 2 locally produced RUTF to treat SAM in Malawi among children aged 6-59 mo. A total of 1874 children were enrolled. Children were assessed every fortnight and participated in the study until they clinically recovered or received 8 wk of treatment. The primary outcome was recovery (weight-for-height Z score > -2 and no edema). Secondary outcomes were rates of weight and height gain. Survival analysis was used to compare the recovery rates. Recovery among children receiving 25% milk RUTF was greater than children receiving 10% milk RUTF, 64% compared with 57% after 4 wk, and 84% compared with 81% after 8 wk (P < 0.001). Children receiving 25% milk RUTF also had higher rates of weight and height gain compared with children receiving 10% milk RUTF. Treating children with SAM with 10% milk RUTF is less effective compared with treatment with the standard 25% milk RUTF. These findings also emphasize that clinical evidence should be examined before recommending any changes to the formulation of RUTF." ]

[ "8215814", "9197912", "11775049", "11411817", "10485635", "11435263", "10865302" ]

[ "Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam.", "Paroxetine efficacy in the treatment of generalized anxiety disorder.", "Pattern of symptom improvement following treatment with venlafaxine XR in patients with generalized anxiety disorder.", "Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial.", "Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder.", "Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder: twenty-four-week placebo-controlled dose-ranging study.", "Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: A 6-month randomized controlled trial." ]

[ "The current study examines whether antidepressants, contrary to current thinking, are safe and effective treatments for generalized anxiety disorder (GAD) not complicated by depression or panic disorder.\n Randomized, double-blind, placebo-controlled, flexible-dose, 8-week treatment study comparing imipramine hydrochloride (mean maximum daily dose, 143 mg), trazodone hydrochloride (255 mg), and diazepam (26 mg).\n Two hundred thirty patients with a DSM-III diagnosis of GAD in whom major depression and panic disorder has been excluded, and who had a Hamilton Anxiety Scale total score of at least 18.\n Seventy-five percent of patients were treated in family practice settings in the community, with the remainder treated in psychiatric practices, either academic or private.\n Patients treated with diazepam showed the most improvement in anxiety ratings during the first 2 weeks of treatment, with somatic symptoms being most responsive. From week 3 through week 8 trazodone achieved comparable, and imipramine somewhat better, anxiolytic efficacy when compared with diazepam, with psychic symptoms of tension, apprehension, and worry being more responsive to the antidepressants. Among completers, moderate to marked improvement was reported by 73% of patients treated with imipramine, 69% of patients treated with trazodone, 66% of patients treated with diazepam, but only 47% of patients treated with placebo. Overall, patients treated with antidepressants reported a higher rate of adverse effects than diazepam-treated patients, but attention rates were the same across all treatments.\n The results of the study need replication, but suggest a potentially important role for antidepressants, particularly imipramine, in patients suffering from GAD.", "Recently, there has been a renewed interest in alternatives to the benzodiazepines for the treatment of generalized anxiety disorder (GAD). The aim of the present study was to compare the efficacy of paroxetine vs. imipramine and 2'-chlordesmethyldiazepam in 81 patients with a DSM-IV diagnosis of GAD. Approximately two-thirds of the patients who completed the study improved greatly or moderately on all three active drugs. During the first 2 weeks of treatment, 2'-chlordesmethyldiazepam treatment resulted in the greatest improvement in anxiety ratings. Both paroxetine and imipramine treatment resulted in more improvement than 2'-chlordesmethyldiazepam by the fourth week of treatment. Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2'-chlordesmethyldiazepam affects predominantly somatic symptoms. Our results suggest that paroxetine is effective for the treatment of GAD.", "The efficacy of anxiolytic drugs in generalized anxiety disorder (GAD) is conventionally assessed by evaluating changes in the total score of psychometric scales such as the Hamilton Rating Scale for Anxiety (HAM-A). The purpose of this pooled analysis of data was to evaluate the efficacy of venlafaxine extended release (XR) on individual items of the HAM-A and the Brief Scale for Anxiety (BSA).\n Data were pooled from 5 studies of patients with GAD who were treated with either venlafaxine XR or placebo for 8 weeks (N = 2,021) and up to 6 months (N = 767). Individual items of the HAM-A and the BSA were examined. and, using the mean changes from baseline to endpoint, an effect size for each item was calculated by dividing the difference between baseline and endpoint values for each item by the standard deviation of this difference. The effect sizes determined for the venlafaxine group were compared with those for the placebo group. Items from each scale that are concordant with the DSM-IV diagnostic criteria for GAD were selected for further examination, and the specific effect sizes of each item were expressed after controlling for placebo effects.\n The effect size of the majority of the 14 items of the HAM-A scale and the 10 items of the BSA scale associated with treatment with venlafaxine XR was greater than with placebo at both 8 weeks and 6 months. Furthermore, the effect sizes at 6 months were generally greater than at 8 weeks in venlafaxine XR-treated patients. Effect sizes associated with venlafaxine XR were greatest for the HAM-A items that were most closely related to diagnostic symptoms of GAD, namely anxious mood, tension, intellectual functioning, and behavior at interview at both 8 weeks and 6 months. Similarly, GAD-related BSA items of inner tension, worrying over trifles, hostile feelings, and muscular tension were associated with the greatest improvements with venlafaxine XR at both time-points.\n The HAM-A and BSA items that most closely corresponded to DSM-IV diagnostic criteria for GAD showed the largest improvement during treatment with venlafaxine XR. This indicates that the specific symptoms of GAD can be treated effectively with venlafaxine XR, both in the short and longer term.", "The objective of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and safety of paroxetine in outpatients with generalized anxiety disorder (GAD).\n Male and female outpatients 18 years and older who met DSM-IV criteria for GAD and had baseline scores of at least 20 on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with paroxetine (20-50 mg/day) or placebo for 8 weeks. The primary efficacy variable was the mean change from baseline in the total score of the HAM-A. Additional key efficacy variables were the change from baseline in the scores of the HAM-A items anxious mood and tension, the anxiety subscale of the Hospital Anxiety and Depression Scale, and the Sheehan Disability Scale (SDS). The proportions of patients fulfilling response and remission criteria at week 8 were also determined.\n The intent-to-treat population included 324 patients. At week 8, compared with the placebo group (N = 163), the paroxetine group (N = 161) had a significantly greater reduction of GAD symptoms on all of the above-mentioned efficacy variables. On the HAM-A anxious mood item, which encompasses the cardinal symptoms of GAD, significantly greater efficacy was observed from week 1 and on the SDS significantly greater improvement was documented in the domain \"social life\" as early as week 4 for paroxetine compared with placebo. In both the last-observation-carried-forward and completer data sets, significantly greater proportions of paroxetine-treated patients achieved response or remission by week 8. Treatment with paroxetine was well tolerated, and the number and type of adverse events recorded in the paroxetine group correspond to the known safety profile of this medication.\n Paroxetine in doses of 20 to 50 mg once daily is effective in the treatment of patients with GAD. Improvement of core symptoms of GAD occurs early and is associated with significant reduction in disability after only 8 weeks of treatment.", "The objective of this randomized, double-blind study was to compare the efficacy and safety of venlafaxine extended release (XR) and buspirone in outpatients with generalized anxiety disorder (GAD) but without concomitant major depressive disorder.\n Male and female outpatients at least 18 years old who met the DSM-IV criteria for GAD and had scores of 18 or higher on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with either venlafaxine XR (75 or 150 mg/day), buspirone (30 mg/day in 3 divided doses), or placebo for 8 weeks. The primary efficacy variables were changes in anxiety as determined by final on-therapy HAM-A total and psychic anxiety scores and Clinical Global Impressions scale (CGI) scores. Other key efficacy variables were HAM-A anxious mood and tension scores and the anxiety subscale scores of the patient-rated Hospital Anxiety and Depression scale (HAD).\n The efficacy analysis included 365 patients and the safety analysis, 405. At week 8, adjusted mean HAM-A psychic anxiety, anxious mood, and tension scores were significantly lower for venlafaxine XR-treated patients than for placebo-treated patients. On the HAD anxiety subscale, venlafaxine XR, 75 or 150 mg/day, was significantly more efficacious than placebo at all time points except weeks 1 (both dosages) and 2 (150-mg/day dosage only) and significantly more efficacious than buspirone at all time points except week 1. On the CGI-Improvement scale, scores for venlafaxine XR (both dosages) and buspirone were numerically superior to those for placebo at all time points, and statistical significance was observed at weeks 3, 4, 6, and 8 for venlafaxine XR and at weeks 6 and 8 for buspirone. The adverse events were not essentially different between treatment groups.\n Venlafaxine XR is an effective, safe, and well-tolerated once-daily anxiolytic agent in patients with GAD without comorbid major depressive disorder. This agent was significantly superior to buspirone on the HAD anxiety subscale. Buspirone demonstrated statistical significance versus placebo on a measure of anxiolytic response.", "Generalised anxiety disorder (GAD) has received less study than other anxiety disorders, particularly its long-term treatment.\n To assess the efficacy and safety of venlafaxine extended release (ER) in patients with GAD.\n A total of 541 out-patients, 18-86 years old, were recruited to this 24-week, placebo-controlled, double-blind study of three fixed doses (37.5, 75 and 150 mg/day) of venlafaxine ER.\n All doses of venlafaxine ER showed efficacy superior to placebo, apparent from week 2, that was sustained throughout the 24-week study for the two higher doses. The discontinuation rate did not differ significantly among the treatment groups.\n Venlafaxine ER is an effective and safe treatment for GAD for up to 6 months.", "Generalized anxiety disorder (GAD) is a chronic disorder that is associated with debilitating psychic and somatic symptoms. Venlafaxine extended-release (XR) capsules have been shown to be effective in short-term treatment of patients with GAD without major depressive disorder (MDD), but long-term data are needed to establish whether this agent confers persistent benefits.\n To compare the 6-month efficacy and safety of a flexible dosage of venlafaxine XR in outpatients with GAD without associated MDD.\n Six-month, randomized, double-blind, placebo-controlled, parallel-group trial conducted May 1996 to October 1997.\n Fourteen outpatient clinics and private psychiatric practices in the United States.\n A total of 251 outpatients aged 18 years or older who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for GAD, had sufficient symptoms to require treatment, and did not have coexisting MDD.\n Participants were randomly assigned to receive either placebo (n=127) or venlafaxine XR (75, 150, or 225 mg/d, as required to control symptoms; n=124) for 28 weeks.\n Changes from baseline in the Hamilton Rating Scale for Anxiety (HAM-A) total score, the HAM-A psychic anxiety factor score, and the Clinical Global Impressions (CGI) scale Severity of Illness and Global Improvement scores, compared by intervention group.\n During weeks 6 through 28, response rates in the venlafaxine XR group were 69% or higher compared with rates of 42% to 46% in the placebo group (P<.001). By an evaluable-patient analysis, venlafaxine XR compared with placebo significantly improved anxiety scores from week 1 or 2 through week 28 on all primary efficacy measures, including the HAM-A total (P<.001), the HAM-A psychic anxiety factor (P<.001), and the CGI scale scores (P<.001). Adjusted mean changes from baseline to week 28 using last-observation-carried-forward methods were for HAM-A, venlafaxine XR -13.4, placebo -8.7 (P<.001); for HAM-A psychic anxiety score, venlafaxine XR -7.4, placebo -4.2 (P<.001); and for CGI-Improvement, venlafaxine XR 2.2, placebo 3.0 (P<.001). The most common treatment-emergent adverse event was nausea, followed by somnolence and dry mouth.\n This study is the first placebo-controlled demonstration of the long-term efficacy of any drug class in treating outpatients with DSM-IV-diagnosed GAD. Venlafaxine XR is an effective, rapidly acting, safe, once-daily agent for both the short- and long-term treatment of anxiety and may provide an important alternative to currently available anxiolytics. JAMA. 2000." ]

[ "10202165", "2807006", "9234921", "15017898", "10202166", "14716113", "14990643", "11844818", "10334517", "10764420", "12654431" ]

[ "Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer.", "Long-term follow-up of potentiation of radiotherapy by cis-platinum in advanced cervical cancer.", "A randomized trial of concurrent chemoradiotherapy versus radiotherapy in advanced carcinoma of the uterine cervix.", "[Comparative parameters of myelotoxicity in patients treated with simultaneous chemotherapy and radiotherapy or only radiotherapy].", "Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.", "Role of chemoradiation in advanced cervical cancer.", "Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01.", "Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.", "Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study.", "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.", "Concurrent mitomycin C, 5-fluorouracil, and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial." ]

[ "On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens -- cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone -- in patients with locally advanced cervical cancer. Women with primary untreated invasive squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix of stage IIB, III, or IVA, without involvement of the para-aortic lymph nodes, were enrolled. The patients had to have a leukocyte count of at least 3000 per cubic millimeter, a platelet count of at least 100,000 per cubic millimeter, a serum creatinine level no higher than 2 mg per deciliter (177 micromol per liter), and adequate hepatic function. All patients received external-beam radiotherapy according to a strict protocol. Patients were randomly assigned to receive one of three chemotherapy regimens: 40 mg of cisplatin per square meter of body-surface area per week for six weeks (group 1); 50 mg of cisplatin per square meter on days 1 and 29, followed by 4 g of fluorouracil per square meter given as a 96-hour infusion on days 1 and 29, and 2 g of oral hydroxyurea per square meter twice weekly for six weeks (group 2); or 3 g of oral hydroxyurea per square meter twice weekly for six weeks (group 3).\n The analysis included 526 women. The median duration of follow-up was 35 months. Both groups that received cisplatin had a higher rate of progression-free survival than the group that received hydroxyurea alone (P<0.001 for both comparisons). The relative risks of progression of disease or death were 0.57 (95 percent confidence interval, 0.42 to 0.78) in group 1 and 0.55 (95 percent confidence interval, 0.40 to 0.75) in group 2, as compared with group 3. The overall survival rate was significantly higher in groups 1 and 2 than in group 3, with relative risks of death of 0.61 (95 percent confidence interval, 0.44 to 0.85) and 0.58 (95 percent confidence interval, 0.41 to 0.81), respectively.\n Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer.", "Between January 1982 and January 1983 all patients with advanced cervical cancer were randomized into three groups: radiotherapy only (group I), radiotherapy plus weekly cis-platinum (group II), and radiation plus twice-weekly cis-platinum (group III). Better initial central control was observed in group III patients. Long-term survival was similar in the three groups. Potentiation of radiotherapy with cis-platinum failed to show any significant improvement in long-term survival.", "The purpose of our study was to determine whether the chemoradiation is better than radiotherapy alone with respect to survival and treatment toxicity in patients with advanced carcinoma of the cervix. From October 1990 to April 1995, a total of 122 patients with advanced cervical carcinoma were included in this study and randomly assigned to either radiotherapy or concurrent chemotherapy and radiotherapy. The patients in the concurrent group received cisplatin, vincristine, and bleomycin every 3 weeks for a total of four courses, in combination with radiotherapy concurrently. Sixty patients were randomized to the concurrent chemoradiotherapy, and 62 were randomized to the radiotherapy alone. A tumor response was observed in 88.3% of the patients in concurrent group and in 74.2% of the patients in radiotherapy group (P = 0.04). After a median follow-up of 46.8 months, the overall disease-free survival and actuarial survival rate at 3 years were 51.7 and 61.7% in the concurrent group, and 53.2 and 64.5% in the radiotherapy group, respectively. Treatment-related toxicity appears to be higher with the combination of radiotherapy and chemotherapy compared with radiotherapy alone (36.7% versus 17.7%, P = 0.02). However, analysis by Kaplan-Meier method showed that the actuarial survival was not statistically different between the chemoradiotherapy and radiotherapy groups (mean survival time: 38.1 months versus 41.5 months, P = 0.27). In conclusion, this study showed that concurrent multiagent chemoradiotherapy did not prove to be a superior definitive therapy over radiotherapy alone for patients with advanced cervical carcinoma.", "The Modern oncological treatment usually consists of the different kind of the therapies. Improvement of survival and local control of disease could be possible with combined treatments: surgery, radiotherapy, chemotherapy, etc. However if these treatments are given concomitantly one can expect higher toxicity.\n Comparation of parameters of miclotoxicity: red blood cell count, white blood cell count, platelets and hemoglobin in patients with advanced cervical carcinoma treated with concomitant chemo-radiotherapy versus radiotherapy alone.\n From 1997-1999, we performed prospective, by randomised, study, and 80 patients were divided in two groups: Group A--40 patients treated with concomitant chemo-radiotherapy versus, Group B--40 patients treated with radiotherapy alone. Red blood cell count, white blood cell count, platelets and hemoglobin were evaluated before enrollement, during the theraphy, after 3 and 6 months, according to CTC toxicity criteria.\n We perform statistical analysis using H2 test, and we found no significant difference in mild nad severe toxicity in red blood cell count, white blood cell count, platelets and hemoglobin among groups.", "Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer.\n Women with bulky stage IB cervical cancers (tumor, > or =4 cm in diameter) were randomly assigned to receive radiotherapy alone or in combination with cisplatin (40 mg per square meter of body-surface area once a week for up to six doses; maximal weekly dose, 70 mg), followed in all patients by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external radiotherapy, and adjuvant hysterectomy was performed three to six weeks later.\n The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin, as compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95 percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent confidence interval, 0.34 to 0.86), respectively. The rates of both progression-free survival (P<0.001) and overall survival (P=0.008) were significantly higher in the combined-therapy group at four years. In the combined-therapy group there were higher frequencies of transient grade 3 (moderate) and grade 4 (severe) adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group) and adverse gastrointestinal effects (14 percent vs. 5 percent).\n Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers.", "A prospective randomized study was conducted in our department of Radiotherapy, Regional Institute of Medical Sciences, Imphal to evaluating the role of chemoradiation in the management of advanced inoperable cervical cancer (stage IIB-IIIB) taking only radiation treatment as control spanning the period 1996-1999. Of the fifty patients accumulated in the study group, three patients did not complete treatment, one expired due to other causes and three were lost to follow up. Likewise, of the forty-six patients in the control group, one patient did not complete treatment and 4 were lost to follow up. Thus only 43 and 41 patients were available for the result analysis for the study and control groups respectively. The early treatment response as assessed after two months of treatment conclusion were 79.1%, 13.9%, 93.0% and 58.5%, 31.7%, 90.2% as complete response (CR), partial response (PR), and total response (TR) respectively for the study and control groups. Our patients included in this study had a median follow up of 35 months and 33 months for study and control groups respectively. For this follow up, the disease-free survival, survival with disease and overall survival were 67.4%, 7.0%, 74.4% and 43.9%, 12.2%, 56.1% for study and control groups respectively. There was an increase in early side-effects in the chemoradiation group but the difference was not significant. Because of the early side effects, treatment delays ensued in 7 patients (16.3%) and in 3 patients (7.3%) in the study and control groups respectively. There was no significant increase in the late treatment toxicities in both the groups.", "To report mature results of a randomized trial that compared extended-field radiotherapy (EFRT) versus pelvic radiotherapy with concomitant fluorouracil and cisplatin (CTRT) in women with locoregionally advanced carcinomas of the uterine cervix.\n Four hundred three women with cervical cancer were randomly assigned to receive either EFRT or CTRT. Patients were eligible if they had stage IIB to IVA disease, stage IB to IIA disease with a tumor diameter > or = 5 cm, or positive pelvic lymph nodes. Patients were stratified by stage and by method of lymph node evaluation.\n The median follow-up time for 228 surviving patients was 6.6 years. The overall survival rate for patients treated with CTRT was significantly greater than that for patients treated with EFRT (67% v 41% at 8 years; P <.0001). There was an overall reduction in the risk of disease recurrence of 51% (95% CI, 36% to 66%) for patients who received CTRT. Patients with stage IB to IIB disease who received CTRT had better overall and disease-free survival than those treated with EFRT (P <.0001); 116 patients with stage III to IVA disease had better disease-free survival (P =.05) and a trend toward better overall survival (P =.07) if they were randomly assigned to CTRT. The rate of serious late complications of treatment was similar for the two treatment arms.\n Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects.", "To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix.\n A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without chemotherapy (arm 2).\n A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P =.33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62).\n This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2) to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.", "In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities.\n All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix. Patients underwent standard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB, III, or IVA. Negative cytologic washings and para-aortic lymph nodes were required for entry. Patients were randomized to receive either standard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU.\n Of 388 randomized patients, 368 were eligible; 177 were randomized to CF and 191 to HU. Adverse effects were predominantly hematologic or gastrointestinal in both regimens. Severe or life-threatening leukopenia was more common in the HU group (24%) than in the CF group (4%). The difference in progression-free survival (PFS) was statistically significant in favor of the CF group (P = .033). The sites of progression in the two treatment groups were not substantially different. Survival was significantly better for the patients randomized to CF (P = .018).\n This study demonstrates that for patients with locally advanced carcinoma of the cervix, the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU, and with manageable toxicity.", "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.", "This is a prospective, Phase III multicenter randomized trial to assess the effectiveness of concurrent intravenous mitomycin C, oral 5-fluorouracil (5-FU), and radiotherapy (RT) in locally advanced carcinoma of the cervix.\n Between January 1988 and November 1994, 926 patients with locally advanced carcinoma of the cervix, FIGO Stage IIB-IVA, were entered into this study. The patients were randomized into four arms, as follows: Arm 1: conventional RT; Arm 2: conventional RT and adjuvant chemotherapy; Arm 3: conventional RT plus concurrent chemotherapy; Arm 4: conventional RT plus concurrent chemotherapy and adjuvant chemotherapy. Concurrent chemotherapy consisting of intravenous mitomycin C at 10 mg/m(2) was given on Days 1 and 29, and oral 5-FU at 300 mg/day was administered on Days 1-14 and 29-42 during RT. Adjuvant chemotherapy of 5-FU orally at 200 mg/day was given for three courses of 4 weeks, with a 2-week rest every 6 weeks. Six centers participated in the trial.\n The median follow-up time was 89 months. Acute side effects were generally higher in concurrent arms, but most of the patients tolerated the treatment well. Bone marrow toxicity was also higher in concurrent arms. The 5-year actuarial disease-free survival (DFS) was 48.2%, 54.1%, 64.5%, and 59.7% for arms 1, 2, 3, and 4, respectively. The pattern of failure revealed a significant increase in locoregional recurrence in the nonconcurrent chemoradiotherapy arm. The local recurrence was 25.5%, 20.6%, 14.3%, and 17.6% for arms 1, 2, 3, and 4, respectively. The metastatic rates were not significantly different in all four arms. At the time of analysis, there were no increases in late side effects, especially in gastrointestinal and genitourinary systems.\n Concurrent chemotherapy, mitomycin C, and 5-FU together with conventional RT showed an improved DFS rate when compared with conventional RT alone in patients with locally advanced carcinoma of the cervix." ]

[ "20120790", "20120791", "15213046", "12730420", "12600867", "17409323", "21596735", "12637400", "17065044", "17974365", "18207017", "20412605", "18326610", "16015266", "17199068", "18996870", "18996930", "17302515", "15766997" ]

[ "Preventing low birthweight through maternal multiple micronutrient supplementation: a cluster-randomized, controlled trial in Indramayu, West Java.", "A comparative evaluation of multiple micronutrient and iron-folic acid supplementation during pregnancy in Pakistan: impact on pregnancy outcomes.", "Effect of multimicronutrient supplementation on gestational length and birth size: a randomized, placebo-controlled, double-blind effectiveness trial in Zimbabwe.", "A micronutrient-fortified beverage prevents iron deficiency, reduces anemia and improves the hemoglobin concentration of pregnant Tanzanian women.", "Multiple micronutrient supplementation during pregnancy does not lead to greater infant birth size than does iron-only supplementation: a randomized controlled trial in a semirural community in Mexico.", "Vitamins and perinatal outcomes among HIV-negative women in Tanzania.", "Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial.", "Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial.", "Lower rate of preeclampsia after antioxidant supplementation in pregnant women with low antioxidant status.", "Prenatal multiple micronutrient supplementation has greater impact on birthweight than supplementation with iron and folic acid: a cluster-randomized, double-blind, controlled programmatic study in rural Niger.", "Effect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double-blind cluster-randomised trial.", "Effect of multiple-micronutrient supplementation on maternal nutrient status, infant birth weight and gestational age at birth in a low-income, multi-ethnic population.", "Effects of prenatal food and micronutrient supplementation on infant development: a randomized trial from the Maternal and Infant Nutrition Interventions, Matlab (MINIMat) study.", "Effects of prenatal multimicronutrient supplements on birth weight and perinatal mortality: a randomised, controlled trial in Guinea-Bissau.", "Multimicronutrient supplementation for undernourished pregnant women and the birth size of their offspring: a double-blind, randomized, placebo-controlled trial.", "Effects of maternal multiple micronutrient supplementation on fetal growth: a double-blind randomized controlled trial in rural Burkina Faso.", "Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial.", "Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women.", "Effects of antenatal multiple micronutrient supplementation on birthweight and gestational duration in Nepal: double-blind, randomised controlled trial." ]

[ "Micronutrient deficiencies may contribute to a higher incidence of low birthweight (LBW). UNICEF/United Nations University/World Health Organization jointly proposed a formulation for a multiple micronutrient supplement for pregnant women, and several effectiveness trials were conducted to assess its impact.\n To evaluate the efficacy of prenatal multiple micronutrient supplementation for improving birth size, pregnancy outcome, and maternal micronutrient status in comparison with iron-folic acid supplementation.\n We carried out a cluster-randomized, controlled trial in Indramayu, Indonesia, involving 843 pregnant women. Of these, 432 received multiple micronutrients and 411 received iron-folic acid. Fieldworkers visited the women daily to observe supplement consumption and record fetal loss and mortality.\n The mean number of supplements consumed during pregnancy and 30 days postpartum was high (136 in the group receiving multiple micronutrients and 140 in the iron-folic acid group). The women consumed the supplements on average 5 days per week. Although there were no significant differences between the groups in the percentage of infants with LBW there was a trend toward a lower incidence of LBW in the group receiving multiple micronutrients (6.3% vs. 7.3%), and the mean birthweight was 40 g higher in the group receiving multiple micronutrients than in the iron-folic acid group, although the difference was not significant. Among those who consumed 90 or more supplements during pregnancy, women taking multiple micronutrients had a 3.3% combined rate of miscarriage, stillbirth, or neonatal death, as compared with 6.9% for those taking iron-folic acid only (p < .049). The anemia rates in the two groups were similar after supplementation, even though the amount of iron in the multiple micronutrient supplement was half that in the iron-folic acid supplement. Serum retinol was higher in the group receiving multiple micronutrients.\n Multivitamin supplementation use among pregnant women is as effective as iron-folic acid in improving anemia status and appears to have other benefits for maternal and child nutritional status.", "Maternal micronutrient deficiencies are widespread in Pakistan and are potentially associated with maternal undernutrition and intrauterine growth retardation. Intervention strategies largely consist of administration of iron-folic acid supplements during pregnancy.\n We evaluated the acceptability of multiple micronutrient supplementation and its potential benefits on pregnancy outcomes and maternal micronutrient status in a cohort of pregnant women in rural and urban Sindh through a cluster-randomized design.\n We randomly assigned 2378 pregnant women to receive either iron-folic acid or multiple micronutrient supplements. The supplements were administered fortnightly by community health workers who performed home visits to assess tolerance and observe the mothers.\n The women in both groups consumed about 75% of the supplements provided, and few reported adverse effects such as vomiting, abdominal pain, etc. There was a small (70 g) but significant increase in birthweight among infants of mothers receiving multiple micronutrients as compared with infants of mothers receiving iron-folic acid supplements (2.95 +/- 0.6 vs. 2.88 +/- 0.5 kg, p = .01). This translated into a 10% reduction (p < 0.17) in the proportion of low-birthweight infants among infants of mothers receiving multiple micronutrients. Although stillbirth rates were comparable in the two groups, the early neonatal mortality rate in the group receiving multiple micronutrients was higher, although not significantly, than that in the group receiving iron-folic acid (43.2 vs. 23.5 deaths per 1000 live births; RR = 1.64; 95% CI, 0.94 to 2.87). Comparable reductions in anemia (hemoglobin < 11 g/dL) were observed, although the proportion with low iron stores (assessed by serum ferritin) was lower in the iron-folic acid group in the postnatal period. Although the proportion of women with subclinical vitamin A deficiency after supplementation did not differ between the two groups, the iron-folic acid group had a higher proportion with lower serum zinc levels in the immediate postpartum period.\n These data suggest that multiple micronutrient supplements are well tolerated during pregnancy, but the effect on birthweight is modest. The observed effect on early neonatal mortality suggests the need for further studies and careful assessment of the intervention in health system settings.", "Multiple micronutrient deficiencies may contribute to low birth weight, which is a major global determinant of mortality.\n We assessed the effect of prenatal multimicronutrient supplementation on gestational length and birth size.\n We conducted a randomized, placebo-controlled, double-blind effectiveness trial among antenatal care attendees in Harare, Zimbabwe. Pregnant women (22-35 wk of gestation) were randomly allocated to receive a multimicronutrient or placebo supplement daily until delivery. Supplementation with iron and folic acid was part of antenatal care.\n Of 1669 women, birth data were available from 1106 (66%), of whom 360 (33%) had HIV infection. The mean gestational length was 39.1 wk, and 16.6% of the women had a gestational length < 37 wk. The mean birth weight was 3030 g, and 10.5% of the infants had a birth weight < 2500 g. Multimicronutrient supplementation was associated with tendencies for increased gestational length (0.3 wk; 95% CI: -0.04, 0.6 wk; P = 0.06), birth weight (49 g; -6, 104 g; P = 0.08), and head circumference (0.2 cm; -0.02, 0.4 cm; P = 0.07) but was not associated with low birth weight (birth weight < 2500 g) (relative risk: 0.84; 0.59, 1.18; P = 0.31). The effect of multimicronutrient supplementation on birth weight was not significantly different between HIV-uninfected (26 g; -38, 91 g) and HIV-infected (101 g; -3, 205 g) subjects (interaction, P > 0.10).\n Antenatal multimicronutrient supplementation may be one strategy to increase birth size.", "Maternal malnutrition continues to be a major contributor to adverse reproductive outcomes in developing countries, despite longstanding efforts to fortify foods or to distribute medicinal supplements to pregnant women. The objective of this study was to test the effect of a micronutrient-fortified beverage containing 11 micronutrients (iron, iodine, zinc, vitamin A, vitamin C, niacin, riboflavin, folate, vitamin B-12, vitamin B-6 and vitamin E) on the hemoglobin, iron and vitamin A status of pregnant women in Tanzania. A group of 259 pregnant women with gestational ages of 8 to 34 wk were enrolled in a randomized double-blind controlled trial in which study women received 8 wk of supplementation. Hemoglobin, ferritin and dried blood spot retinol were measured at baseline and at the end of the supplementation period. The supplement resulted in a 4.16 g/L increase in hemoglobin concentration and a 3 micro g/L increase in ferritin and reduced the risk of anemia and iron deficiency anemia by 51 and 56%, respectively. The risk of iron deficiency was reduced by 70% among those who had iron deficiency at baseline and by 92% among those who had adequate stores. The micronutrient-fortified beverage may be a useful and convenient preventative measure, one that could help improve the nutritional status of women both before and during pregnancy and thereby help avoid some of the potential maternal and fetal consequences of micronutrient deficiencies.", "Little is known about the benefits of prenatal multivitamin and mineral supplements in reducing low birth weight.\n We conducted a randomized, double-blind clinical trial in semirural Mexico to compare the effects of multiple micronutrient (MM) supplements with those of iron supplements during pregnancy on birth size.\n Pregnant women (n = 873) were recruited before 13 wk of gestation and received supplements 6 d/wk at home, as well as routine antenatal care, until delivery. Both supplements contained 60 mg Fe, but the MM group also received 1-1.5 times the recommended dietary allowances of several micronutrients.\n At recruitment, the women in the 2 groups were not significantly different in age, parity, economic status, height, or hemoglobin concentration but differed significantly in marital status (4.6% and 2.0% of women in the MM and iron-only groups, respectively, were single mothers) and mean (+/- SD) body mass index (in kg/m(2); 24.6 +/- 4.3 and 23.8 +/- 3.9 in the iron-only and MM groups, respectively). Losses to follow-up (25%) and compliance (95%) did not differ significantly between the groups. In intent-to-treat analyses (MM group: n = 323; iron-only group: n = 322), mean (+/- SD) birth weight (2.981 +/- 0.391 and 2.977 +/- 0.393 kg in the MM and iron-only groups, respectively) and birth length (48.61 +/- 1.82 and 48.66 +/- 1.83 cm in the MM and iron-only groups, respectively) did not differ significantly between the groups.\n These findings suggest that MM supplementation during pregnancy does not lead to greater infant birth size than does iron-only supplementation.", "Prematurity and low birth weight are associated with high perinatal and infant mortality, especially in developing countries. Maternal micronutrient deficiencies may contribute to these adverse outcomes.\n In a double-blind trial in Dar es Salaam, Tanzania, we randomly assigned 8468 pregnant women (gestational age of fetus, 12 to 27 weeks) who were negative for human immunodeficiency virus infection to receive daily multivitamins (including multiples of the recommended dietary allowance) or placebo. All the women received prenatal supplemental iron and folic acid. The primary outcomes were low birth weight (<2500 g), prematurity, and fetal death.\n The incidence of low birth weight was 7.8% among the infants in the multivitamin group and 9.4% among those in the placebo group (relative risk, 0.82; 95% confidence interval [CI], 0.70 to 0.95; P=0.01). The mean difference in birth weight between the groups was modest (67 g, P<0.001). The rates of prematurity were 16.9% in the multivitamin group and 16.7% in the placebo group (relative risk, 1.01; 95% CI, 0.91 to 1.11; P=0.87), and the rates of fetal death were 4.3% and 5.0%, respectively (relative risk, 0.87; 95% CI, 0.72 to 1.05; P=0.15). Supplementation reduced both the risk of a birth size that was small for gestational age (<10th percentile; 10.7% in the multivitamin group vs. 13.6% in the placebo group; relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.001) and the risk of maternal anemia (hemoglobin level, <11 g per deciliter; relative risk, 0.88; 95% CI, 0.80 to 0.97; P=0.01), although the difference in the mean hemoglobin levels between the groups was small (0.2 g per deciliter, P<0.001).\n Multivitamin supplementation reduced the incidence of low birth weight and small-for-gestational-age births but had no significant effects on prematurity or fetal death. Multivitamins should be considered for all pregnant women in developing countries. (ClinicalTrials.gov number, NCT00197548 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.", "To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk.\n Randomised, blinded, placebo controlled clinical trial.\n Tertiary public hospital in Mexico City.\n Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery.\n Supplementation with a medical food-bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo-during pregnancy.\n Development of pre-eclampsia/eclampsia.\n 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ(2) = 19.41; P < 0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ(2) = 3.76; P = 0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P = 0.004; absolute risk reduction 0.09, 0.05 to 0.14).\n Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846.", "To assess the impact on birth size and risk of low birth weight of alternative combinations of micronutrients given to pregnant women.\n Double blind cluster randomised controlled trial.\n Rural community in south eastern Nepal.\n 4926 pregnant women and 4130 live born infants.\n 426 communities were randomised to five regimens in which pregnant women received daily supplements of folic acid, folic acid-iron, folic acid-iron-zinc, or multiple micronutrients all given with vitamin A, or vitamin A alone (control).\n Birth weight, length, and head and chest circumference assessed within 72 hours of birth. Low birth weight was defined <2500 g.\n Supplementation with maternal folic acid alone had no effect on birth size. Folic acid-iron increased mean birth weight by 37 g (95% confidence interval -16 g to 90 g) and reduced the percentage of low birthweight babies (<2500 g) from 43% to 34% (16%; relative risk=0.84, 0.72 to 0.99). Folic acid-iron-zinc had no effect on birth size compared with controls. Multiple micronutrient supplementation increased birth weight by 64 g (12 g to 115 g) and reduced the percentage of low birthweight babies by 14% (0.86, 0.74 to 0.99). None of the supplement combinations reduced the incidence of preterm births. Folic acid-iron and multiple micronutrients increased head and chest circumference of babies, but not length.\n Antenatal folic acid-iron supplements modestly reduce the risk of low birth weight. Multiple micronutrients confer no additional benefit over folic acid-iron in reducing this risk.", "To investigate maternal and neonatal outcomes after antioxidant supplementation relatively early in pregnancy (8 to 12 weeks) for pregnant women with low antioxidant status.\n A randomized, double-blind, placebo-controlled trial of daily antioxidant supplementation was performed on pregnant women screening positive for low antioxidant status at 8 to 12 weeks of gestation. Low antioxidant status was defined as a superoxidedismutase (SOD) level below 1102 U/g Hb or 164 U/mL. The supplementation group received the following antioxidants daily: vitamins A (1000 IU), B6 (2.2 mg), B12 (2.2 microg), C (200 mg), and E (400 IU), folic acid (400 microg), N-acetylcysteine (200 mg), Cu (2 mg), Zn (15 mg), Mn (0.5 mg), Fe (30 mg), calcium (800 mg), and selenium (100 microg). The control group received Fe (30 mg) and folic acid (400 microg). Maternal (preeclampsia, abortion, and hypertension) and perinatal outcomes were assessed.\n In the supplementation group (29 subjects), we observed 2 cases of preeclampsia (6.8%, 1 mild and 1 severe), 1 of IUGR (birth weight 2300 g at 38 weeks), and 1 preterm delivery. In the control group (31 subjects), there were 8 abortions, 9 cases of preeclampsia (29%, 6 mild and 3 severe) with perinatal outcome: 3 preterm delivery cases and 1 IUGR (birth weight 2030 g at 39 weeks). Preeclampsia was significantly less frequent in the supplementation group when compared to the control group (2 vs. 9 cases, p = 0.043, OR = 0.18 [95% CI: 0.03, 0.92]). Finally we focused on the prediction of preeclampsia at 8 to 12 weeks. Combined sensitivity of markers of antioxidant status (SOD slutathione peroxidase, [GPx], and total anti-oxidant status [TAS]) was 33% (false-positive rate of 4.5%).\n Antioxidant supplementation was associated with better maternal and perinatal outcome in pregnant women with low antioxidant status than control supplementation with iron and folate alone. In a selected population already screened positive for low SOD, preeclampsia can be detected in 33% of asymptomatic cases in the first trimester using SOD, GPx, and TAS. It seems feasible that panels of both biochemical and molecular markers may be clinically useful in the prediction of this disease.", "Micronutrient deficiencies during pregnancy are associated with adverse pregnancy outcomes, including reduced birthweight. Low birthweight is associated with increased risk of infant mortality and growth failure.\n To assess the effects of prenatal supplementation with UNIMMAP (United Nations International Multiple Micronutrient Preparation) compared with iron/folic acid on average birthweight and incidence of low birthweight.\n Pregnant women from 78 villages in Niger were included in a cluster-randomized, double-blinded, controlled supplementation trial. Baseline, monthly follow-up, and birth data were collected. Cluster analysis was conducted to assess differences in mean birthweight and incidence of low birthweight between groups using multiple linear regression models. Analyses were stratified by nutrition status and duration of supplementation.\n Of the 3,670 women recruited, 2,550 completed the study and provided complete birthweight data (1,328 received multiple micronutrients and 1,222 received iron/folic acid). Mean birthweight was significantly higher (67 g, p < .001) with multiple micronutrients (3,092 +/- 190 g) than with iron/folic acid (3,025 +/- 205 g); this corresponded to a 14% fall in the incidence of low birthweight (from 8.4% with multiple micronutrients to 7.2% with folic acid fortification). The impact of multiple micronutrients was greater when the supplements were taken for more than 150 days. The incidence of low birthweight was further reduced in women who entered pregnancy with a poorer nutrition status.\n Prenatal supplementation with multiple micronutrients had a greater positive impact on birthweight than supplementation with iron/folic acid. Our data suggest that prenatal supplementation with multiple micronutrients as part of a prenatal care package in addition to interventions to promote improved maternal prepregnancy nutrition status is an important strategy to increase birthweight and reduce the incidence of low birthweight.", "Maternal nutrient supplementation in developing countries is generally restricted to provision of iron and folic acid (IFA). Change in practice toward supplementation with multiple micronutrients (MMN) has been hindered by little evidence of the effects of MMN on fetal loss and infant death. We assessed the effect of maternal supplementation with MMN, compared with IFA, on fetal loss and infant death in the setting of routine prenatal care services.\n In a double-blind cluster-randomised trial in Lombok, Indonesia, we randomly assigned 262 midwives to distribute IFA (n=15 ,86) or MMN (n=15,804) supplements to 31 290 pregnant women through government prenatal care services that were strengthened by training and community-based advocacy. Women obtained supplements, to be taken daily, every month from enrolment to 90 days post partum. The primary outcome was early infant mortality (deaths until 90 days post partum). Secondary outcomes were neonatal mortality, fetal loss (abortions and stillbirths), and low birthweight. Analysis was by intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN34151616.\n Infants of women consuming MMN supplements had an 18% reduction in early infant mortality compared with those of women given IFA (35.5 deaths per 1000 livebirths vs 43 per 1000; relative risk [RR] 0.82, 95% CI 0.70-0.95, p=0.010). Infants whose mothers were undernourished (mid upper arm circumference <23.5 cm) or anaemic (haemoglobin <110 g/L) at enrolment had a reduction in early infant mortality of 25% (RR 0.75, 0.62-0.90, p=0.0021) and 38% (RR 0.62, 0.49-0.78, p<0.0001), respectively. Combined fetal loss and neonatal deaths were reduced by 11% (RR 0.89, 0.81-1.00, p=0.045), with significant effects in undernourished (RR 0.85, 0.73-0.98, p=0.022) or anaemic (RR 0.71, 0.58-0.87, p=0.0010) women. A cohort of 11 101 infants weighed within 1 h of birth showed a 14% (RR 0.86, 0.73-1.01, p=0.060) decreased risk of low birthweight for those in the MMN group, with a 33% (RR 0.67, 0.51-0.89, p=0.0062) decrease for infants of women anaemic at enrolment.\n Maternal MMN supplementation, as compared with IFA, can reduce early infant mortality, especially in undernourished and anaemic women. Maternal MMN supplementation might therefore be an important part of overall strengthening of prenatal-care programmes.", "Poor nutrient intake during pregnancy can adversely affect both infant and maternal health. The aim was to investigate the efficacy of multiple-micronutrient supplementation during pregnancy in a socially deprived population in the developed world. We conducted a randomised, double-blind, placebo-controlled trial of multiple-micronutrient supplementation including 20 mg Fe and 400 microg folic acid, from the first trimester of pregnancy in 402 mothers, in East London, UK. Nutrient status was measured at recruitment, and at 26 and 34 weeks of gestation. Infants were weighed at birth. At recruitment the prevalence of anaemia was 13 %, vitamin D insufficiency 72 %, thiamin deficiency 12 % and folate deficiency 5 %, with no differences between groups. Only 39 % of women completed the study; rates of non-compliance were similar in both groups. Intention-to-treat analysis showed that participants receiving treatment had higher mean Hb at 26 weeks of gestation (110 (sd 10) v.108 (sd 10) g/l; P = 0.041) and 34 weeks of gestation (113 (sd 12) v.109 (sd 10) g/l; P = 0.003) and packed cell volume concentrations at 26 weeks of gestation (0.330 (sd 0.025) v. 0.323 (sd 0.026) l/l; P = 0.011) and 34 weeks of gestation (0.338 (sd 0.029) v. 0.330 (sd 0.028) l/l; P = 0.014) compared with controls. Analysis of compliant women showed supplemented women had higher median concentrations of serum ferritin, erythrocyte folate and 25-hydroxyvitamin D later in gestation than controls. In the compliant subset (n 149), placebo mothers had more small-for-gestational age (SGA) infants (eight SGA v. thirteen; P = 0.042) than treatment mothers. Baseline micronutrient deficiencies were common; the multiple-micronutrient supplement was well-tolerated and improved nutrient status. Multiple-micronutrient supplements from early pregnancy may be beneficial and larger studies are required to assess impact on birth outcomes and infant development.", "Few data exist for the effects of multiple micronutrient (MM) or food supplementation to undernourished pregnant women on their offsprings' development.\n We aimed to compare the effects on infant development of early (8-10 wk gestation) or usual ( approximately 17 wk gestation) supplementation with food and MM, 30 mg Fe + 400 microg folate, or 60 mg Fe + 400 microg folate.\n A large, randomized, controlled trial of pregnancy supplementation was conducted in Bangladesh. A subsample of infants (n = 2853) were assessed on 2 problem-solving tests (support and cover tests), the motor index of the Bayley Scales of Infant Development, and Wolke's behavior ratings at 7 mo of age.\n There were no significant effects of any intervention in the group as a whole. However, infants of undernourished mothers [body mass index (BMI; in kg/m2) < 18.5] who received early food supplementation performed slightly but significantly (P = 0.035) better on the support test than did infants of mothers who received usual food supplementation (z score: 0.17; 95% CI: 0.01, 0.33). There were no benefits in infants of higher-BMI mothers (P = 0.024 for BMI x food interaction). Children of low-BMI mothers who received MMs had slightly better motor scores (z score: 0.28; 95% CI: 0.08, 0.48) and activity ratings (z score: 0.24; 95% CI: 0.037, 0.45) than did those who received 30 mg Fe + 400 microg folate, whereas other children did not benefit (P = 0.05 for both motor scores and BMI x micronutrients and for activity and BMI x micronutrients).\n Small benefits from early food and MM supplementation were found in infants of low-BMI but not of high-BMI mothers. However, the benefits were of doubtful functional importance, and longer follow-up is required to determine programmatic implications.", "To assess the effects of daily prenatal multimicronutrient supplementation on birth weight (BW) and perinatal mortality.\n Randomised, controlled, double masked trial.Setting:Urban Guinea-Bissau, West Africa.\n A total of 2100 pregnant women (22+/-7 weeks pregnant at entry) were recruited through antenatal clinics, of which 1670 (79.5%) completed the trial. BW was available for 1100 live born babies.\n Identical-looking supplements containing one (MN-1) or two (MN-2) Recommended Dietary Allowances (RDA) of 15 micronutrients, or iron and folic acid (control).\n Mean BW among 1100 live born infants was 3050+/-498 g with 11.9% being low birth weight (LBW, BW < 2500 g). Perinatal mortality was 82 per 1000 deliveries (N = 1670), and neonatal mortality 45 per 1000 live births (N = 1599). Mean BW in MN-1 (n = 360) and MN-2 (n = 374) groups were 53 [-19; 125] and 95 [24; 166] g higher than controls (n = 366). Proportion of LBW was 13.6% in control, and 12.0 and 10.1% in the MN-1 and MN-2 groups, respectively (P = 0.33). Among anaemic women (30%), MN-2 increased BW with 218 [81; 354] g compared to controls, with a decreased risk of LBW of 69 [27; 87]%. There were apparently no differences in perinatal mortality between groups.\n Prenatal micronutrient supplementation increased BW but did not reduce perinatal mortality in this study. Multimicronutrient supplementation with two RDA should be considered in future programmes to reduce the proportion of LBW.", "To evaluate the effect of multimicronutrient supplementation for undernourished pregnant women on the birth size of their offspring, incidence of low-birth-weight infants (<2500 g), and early neonatal morbidity.\n Randomized, double-blind, placebo-controlled trial.\n Tertiary care hospital.\n Two hundred pregnant women (of 13 465 approached) with a body mass index (calculated as weight in kilograms divided by the square of height in meters) of less than 18.5 and/or a hemoglobin level of 7 to 9 g/dL were enrolled at 24 to 32 weeks of gestation. One hundred forty-six neonates (73.0%) were available for analysis of birth size and 170 (85.0%) for analysis of morbidity in the 7 days after delivery. Intervention The micronutrient supplementation group (n = 99) received a multimicronutrient supplement containing 29 vitamins and minerals once a day, from enrollment until delivery (median duration, 58 days; interquartile range, 37-77 days; compliance, 87%). The comparison group (n = 101) received placebo for 52 (15-66) days, with 85% compliance. All subjects also received supplements of iron (given in the form of ferrous sulfate, containing 60 mg of elemental iron), 60 mg/d, and folic acid, 500 mug/d.\n Birth weight, length, midarm circumference, incidence of low birth weight, and early neonatal morbidity.\n Infants in the micronutrient group were heavier by 98 g (95% confidence interval [CI], -16 to 213 g) and measured 0.80 cm (95% CI, 0.03-1.57 cm) longer and 0.20 cm (95% CI, 0.04-0.36 cm) larger in midarm circumference compared with the placebo group. Incidence of low birth weight declined from 43.1% to 16.2% with multimicronutrient supplementation a (a 70% decrease; relative risk, 0.30; 95% CI, 0.13-0.71; P=.006), and that of early neonatal morbidity declined from 28.0% to 14.8% (a 58% decrease; relative risk, 0.42; 95% CI, 0.19-0.94; P=.04).\n Compared with iron and folic acid supplementation, the administration of multimicronutrients to undernourished pregnant women may reduce the incidence of low birth weight and early neonatal morbidity.", "Intrauterine growth retardation is a major predictor of child health in developing countries.\n We tested whether providing pregnant women with the UNICEF/WHO/UNU international multiple micronutrient preparation (UNIMMAP), rather than iron and folic acid alone, improved fetal growth and its correlates.\n An intention-to-treat, double-blind, randomized controlled trial including 1426 pregnancies was carried out in rural Burkina Faso. Tablet intake was directly observed.\n Pregnancy outcome was known in 96.3% of the participants. After adjustment for gestational age at delivery, both birth weight (52 g; 95% CI: 4, 100; P = 0.035) and birth length (3.6 mm; 95% CI: 0.8, 6.3; P = 0.012) were significantly higher in the UNIMMAP group. UNIMMAP had a differential effect by percentiles of birth weight and length distributions: the risk of large-for-gestational-age infants was higher in the UNIMMAP group (OR: 1.58; 95% CI: 1.04, 2.38; P = 0.03), although the risk of low birth weight remained unchanged. The effect of UNIMMAP on birth size was modified by maternal body mass index at enrollment and could be more important in multiparous women and women taking sulfadoxine-pyrimethamine. Unexpectedly, the risk of perinatal death was marginally significantly increased in the UNIMMAP group (OR: 1.78; 95% CI: 0.95, 3.32; P = 0.07), and this seemed to affect mainly primiparous women (OR: 3.44; 95% CI: 1.1, 10.7; P for interaction = 0.11).\n Maternal UNIMMAP modestly but significantly increased fetal growth. The resulting benefit on infant growth and survival needs to be assessed. The possible lack of benefit and potential harm in primiparous women should be further investigated. This trial was registered at clinicaltrials.gov as NCT00642408.", "To examine the impact of antenatal supplementation with multiple micronutrients or iron and folic acid compared with folic acid alone on birth weight, duration of gestation, and maternal haemoglobin concentration in the third trimester.\n Cluster randomised double blind controlled trial.\n Two rural counties in north west China.\n 5828 pregnant women and 4697 live births.\n Villages were randomised for all pregnant women to take either daily folic acid (control), iron with folic acid, or multiple micronutrients with a recommended allowance of 15 vitamins and minerals.\n Birth weight, length, and head circumference measured within 72 hours after delivery. Neonatal survival assessed at the six week follow-up visit.\n Birth weight was 42 g (95% confidence interval 7 to 78 g) higher in the multiple micronutrients group compared with the folic acid group. Duration of gestation was 0.23 weeks (0.10 to 0.36 weeks) longer in the iron-folic acid group and 0.19 weeks (0.06 to 0.32 weeks) longer in the multiple micronutrients group. Iron-folic acid was associated with a significantly reduced risk of early preterm delivery (<34 weeks) (relative risk 0.50, 0.27 to 0.94, P=0.031). There was a significant increase in haemoglobin concentration in both iron-folic acid (5.0 g/l, 2.0 to 8.0 g/l, P=0.001) and multiple micronutrients (6.9 g/l, 4.1 to 9.6 g/l, P<0.001) groups compared with folic acid alone. In post hoc analyses there were no significant differences for perinatal mortality, but iron-folic acid was associated with a significantly reduced early neonatal mortality by 54% (relative risk 0.46, 0.21 to 0.98).\n In rural populations in China antenatal supplementation with iron-folic acid was associated with longer gestation and a reduction in early neonatal mortality compared with folic acid. Multiple micronutrients were associated with modestly increased birth weight compared with folic acid, but, despite this weight gain, there was no significant reduction in early neonatal mortality. Pregnant women in developing countries need sufficient doses of iron in nutrient supplements to maximise reductions in neonatal mortality. Trial registration ISRCTN08850194.", "There is no mandatory folic acid fortification of food in Finland. We investigated the effects of mineral water fortified with folic acid, vitamins B6, B12, D and calcium on serum and erythrocyte folate concentrations, serum vitamin B12 and plasma homocysteine concentrations in pregnancy.\n A randomized, controlled, double-blind, parallel-group intervention study.\n Seventy-four pregnant women were recruited from two health care units. The study began at the eleventh week with a two-week run-in period, followed by an eight-week intervention period. The diet was monitored by food records. During the intervention, subjects consumed 1000 mL/day fortified or normal mineral water. The pregnancies were monitored carefully.\n The folate intake was 255 microg/day in the study group and 274 microg/day in the controls. Serum folate concentrations increased in the study group by 10.3 nmol/L and decreased in the controls by 2.7 nmol/L (P<0.05) during the study. The erythrocyte folate concentrations increased in the study group by 360.9 nmol/L and in the controls by 195.6 nmol/L (P=0.004) and serum homocysteine concentrations fell by 1.1 micromol/L and by 0.3 micromol/L, respectively (P<0.05).\n Finnish pregnant women have low dietary folate intake. Fortified mineral water improved folate status and reduced plasma homocysteine concentrations in the pregnant subjects.", "Neonatal mortality is the biggest contributor to global mortality of children younger than 5 years, and low birthweight is a crucial underlying factor. We tested the hypotheses that antenatal multiple micronutrient supplementation would increase infant birthweight and gestational duration.\n We did a double-blind, randomised controlled trial in Dhanusha district, Nepal. Women attending for antenatal care with singleton pregnancies at up to 20 weeks' gestation were invited to participate. Participants were randomly allocated either routine iron and folic acid supplements (control; n=600) or a multiple micronutrient supplement providing a recommended daily allowance of 15 vitamins and minerals (intervention; n=600). Supplementation began at a minimum of 12 weeks' gestation and continued until delivery. Primary outcome measures were birthweight and gestational duration. Analysis was by intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN88625934.\n Birthweight was available for 523/600 infants in the control group and 529/600 in the intervention group. Mean birthweight was 2733 g (SD 422) in the control group and 2810 g (453) in the intervention group, representing a mean difference of 77 g (95% CI 24-130; p=0.004) and a relative fall in the proportion of low birthweight by 25%. No difference was recorded in the duration of gestation (0.2 weeks [-0.1 to 0.4]; p=0.12), infant length (0.3 cm [-0.1 to 0.6]; p=0.16), or head circumference (0.2 cm [-0.1 to 0.4]; p=0.18).\n In a poor community in Nepal, consumption of a daily supplement containing a recommended daily allowance of 15 micronutrients in the second and third trimesters of pregnancy was associated with increased birthweight when compared with a standard iron and folic acid preparation. The effects on perinatal morbidity and mortality need further comparisons between studies. Published online March 3, 2005 http://image.thelancet.com/extras/04art11045web.pdf." ]

[ "1870651", "8310466", "11981123", "8022186", "2359309", "10334615", "2999514", "10596521", "9337506", "8867198", "8669518", "10522717", "11821652", "11838918", "7703820", "4967730" ]

[ "A randomized trial of treatment options for alcohol-abusing workers.", "Long-term outpatient treatment in alcoholics with previous suicidal behavior.", "Prevention of alcohol-related deaths in middle-aged heavy drinkers.", "Rehabilitation for convicted drinking drivers (second offenders): effects on mortality.", "Failure of a 2-hour motivational intervention to alter recurrent drinking behavior in alcoholics with gastrointestinal disease.", "Brief physician advice for alcohol problems in older adults: a randomized community-based trial.", "An experimental test of telephone aftercare contacts with alcoholics.", "Brief intervention for harm reduction with alcohol-positive older adolescents in a hospital emergency department.", "Cue exposure in moderation drinking: a comparison with cognitive-behavior therapy.", "Moderating drinking by correspondence: an evaluation of a new method of intervention.", "A cross-national trial of brief interventions with heavy drinkers. WHO Brief Intervention Study Group.", "Alcohol interventions in a trauma center as a means of reducing the risk of injury recurrence.", "Brief physician advice for problem drinkers: long-term efficacy and benefit-cost analysis.", "Evaluating the effects of a brief motivational intervention for injured drinkers in the emergency department.", "The 'pressures to change' approach to working with the partners of heavy drinkers.", "A six-month controlled evaluation of metronidazole (Flagyl) in chronic alcoholic patients." ]

[ "Employee-assistance programs sponsored by companies or labor unions identify workers who abuse alcohol and refer them for care, often to inpatient rehabilitation programs. Yet the effectiveness of inpatient treatment, as compared with a variety of less intensive alternatives, has repeatedly been called into question. In this study, anchored in the work site, we compared the effectiveness of mandatory in-hospital treatment with that of required attendance at the meetings of a self-help group and a choice of treatment options.\n We randomly assigned a series of 227 workers newly identified as abusing alcohol to one of three rehabilitation regimens: compulsory inpatient treatment, compulsory attendance at Alcoholics Anonymous (AA) meetings, and a choice of options. Inpatient backup was provided if needed. The groups were compared in terms of 12 job-performance variables and 12 measures of drinking and drug use during a two-year follow-up period.\n All three groups improved, and no significant differences were found among the groups in job-related outcome variables. On seven measures of drinking and drug use, however, we found significant differences at several follow-up assessments. The hospital group fared best and that assigned to AA the least well; those allowed to choose a program had intermediate outcomes. Additional inpatient treatment was required significantly more often (P less than 0.0001) by the AA group (63 percent) and the choice group (38 percent) than by subjects assigned to initial treatment in the hospital (23 percent). The differences among the groups were especially pronounced for workers who had used cocaine within six months before study entry. The estimated costs of inpatient treatment for the AA and choice groups averaged only 10 percent less than the costs for the hospital group because of their higher rates of additional treatment.\n Even for employed problem drinkers who are not abusing drugs and who have no serious medical problems, an initial referral to AA alone or a choice of programs, although less costly than inpatient care, involves more risk than compulsory inpatient treatment and should be accompanied by close monitoring for signs of incipient relapse.", "The importance of previous suicidal behavior for the treatment of alcoholics was analyzed in a long-term outpatient treatment study. In a series of 72 patients, 21 patients, (29%), 17 men and 4 women, had previously made at least one suicide attempt or had seriously threatened to kill themselves (3 cases). In comparison with the other alcoholics, those with previous suicidal behavior had a similar attrition rate, they were not more troublesome in treatment, and they had the same rate of favorable outcome during the third year after start of treatment. They differed from the other alcoholics in having a more severe abuse and a less favorable outcome during the initial part of the treatment. In conclusion, our results support the possibility of a long-term outpatient treatment strategy in alcoholics with previous suicide attempts.", "Alcohol as a cause of death in middle-aged patients is well-known from clinical studies. A similarly important correlation in the general population of urban middle-aged men is highly underestimated. Health screening investigations have shown that mortality related to alcohol is five times more common in nonparticipants than in participants. From the mid-70s, the Malmoe Screening and Intervention Study (MSIS) commenced screening investigations including a large number of residents of Malmoe. One goal was to find intervention programs for individuals in an early development of problem drinking, thereby preventing development of serious complications of endstage alcoholism. Herein, we report on the mortality of heavy drinkers (drinking more than 40 g alcohol/day) who were randomized to an intervention or control procedure and whose median survival was 13 years postentry into the MSIS.\n Health-screened men, aged 45-49 years at the initial screening examination and displaying serum gamma-glutamyltransferase (GT) in the top decentile of the GT distribution, were included. A total of 978 out of 11,257 participants met this criteria. A randomized intervention and control study was performed for four years and consisted of men (n = 667) who were born between 1927-1937 and who had two consecutive high GT values within 3 weeks along with heavy alcohol consumption. Half the individuals were informed of the test results and invited for further assessment by a senior physician (n = 365). The principles for brief intervention (DiClemente et al.,1991; Miller and Sanchez, 1993; National Institute of Alcohol Abuse and Alcoholism, 1999) were applied. The other half of the men (n = 302) were left with the information that they had a high GT value and were followed up with laboratory checkups every 2nd year. Mortality was followed up until 1991 and information on deaths was obtained from hospital and police records, necropsy reports, and death certificates.\n Long-term follow-up of mortality for 10-16 years (median, 13 years) showed that 124 of the 978 men had died (12.7%). Autopsy was performed in 96.5% of the cases. In 59 men (48%), death was alcohol-related. In the intervention group (n = 365), 38 (10.4%) men were dead and in the control group (n = 302), 42 (13.9%) men had died. There was a statistically significant difference (p = 0.026), with advantage for treatment. Less alcohol-related deaths and deaths occurring later during follow-up were found in the intervention group compared with the control group. The difference between the groups in total mortality, coronary heart disease, and cancer death was not statistically significant.\n These findings support previous results from the MSIS study indicating that long-term intervention in urban males with alcohol-induced GT increases may be beneficial in terms of survival.", "The mortality experience of convicted drinking drivers (second offenders) (N = 347) randomly assigned to rehabilitation and control groups in two Ontario cities was examined. Over a follow-up period ranging between 8 and 13 years, 14 (11.0%) of the controls and 17 (7.7%) of the rehabilitation group died. Direct comparisons of the randomly assigned control and treatment groups revealed a tendency for lower total mortality and significantly lower mortality from accidental and violent death in those assigned to rehabilitation. Additional comparisons involving a combined rehabilitation group (N = 487) (rehabilitation participants randomly and not randomly assigned) confirmed these observations.", "Patients (N = 114) consecutively entering a medical service with ulcer, cirrhosis or pancreatitis, currently drinking and not currently active in alcoholism treatment were randomly assigned to motivational intervention (MI) or to a control group. Increased utilization of alcoholism programs and self-reported sobriety at 10 weeks were assessed. MI consisted of three separate discussions of the relationship of the patient's disease to continued drinking and the compassionate offer of treatment. Two persons skilled in treatment also met with each MI subject and discussed treatment possibilities for them, facilitating entrance if desired. Patients in both the MI and control group were treated for their medical condition by a medical team and alcoholism treatment was always recommended. Outcome was evaluated for the period from the 10th to the 16th week after return to the community by interview of patient and household contacts and by the keeping of appointments. There were no differences between the control and MI groups, with at least 38% remaining sober for the 10-week interval; the study size was sufficient to detect reliably a 30% improvement. We conclude that additional motivational intervention to this level was not beneficial to the hospitalized alcoholic with disease. There was a statistically significant increase in sobriety among patients who either undertook alcoholism therapy, accepted all parts of the study or kept clinical appointments.", "Alcohol use in older adults is common. It is associated with depression, hypertension, diabetes, drug interactions, accidents, and increased rates of emergency department visits and hospitalizations.\n A controlled clinical trial (Project GOAL--Guiding Older Adult Lifestyles) tested the efficacy of brief physician advice in reducing the alcohol use and use of health care services of older adult problem drinkers. Twenty-four community-based primary care practices in Wisconsin (43 family physicians and internists) participated in the trial. Of the 6073 patients screened, 105 men and 53 women met inclusion criteria and were randomized into a control group (n = 71) or an intervention group (n = 87). Intervention group patients received two 10- to 15-minute physician-delivered counseling sessions that included advice, education, and contracting using a scripted workbook. A total of 146 patients (92.4%) participated in the 12-month follow-up procedure.\n No significant differences were found between the control and intervention groups at baseline in alcohol use, age, socioeconomic status, depression, onset of alcohol use, smoking status, activity level, or use of mood-altering drugs. The older adults who received the physician intervention demonstrated a significant reduction in 7-day alcohol use, episodes of binge drinking, and frequency of excessive drinking (P <.005) compared with the control group at 3, 6, and 12 months after the intervention. There was a 34% reduction in 7-day alcohol use, 74% reduction in mean number of binge-drinking episodes, and 62% reduction in the percentage of older adults drinking more than 21 drinks per week in the intervention group compared with the control group. There were no significant changes in health status. Patterns of health care utilization were not extensively analyzed because of the small number of events.\n This study provides the first direct evidence that brief physician advice can decrease alcohol use by older adults in community-based primary care practices.", "Alcoholics from two hospital-based treatment centers participated in an experimental test of the effects of extended aftercare on inpatient recovery rates. At discharge from inpatient treatment, subjects were randomly assigned either to an experimental group scheduled to be called by a center counselor every 2 weeks for 1 year or to a control group that experienced only the usual treatment. Follow-up interviews conducted approximately 12 months after hospital discharge found that the experimental group had no higher recovery rates than the control group. There was weak evidence that the calls reduced the burden that alcoholics place on community control and service agencies. There was no evidence that either the phone calls were more effective for some patients than for others or that some kinds of phone calls were more effective than others. Although most subjects said they liked the calls, wanted them to continue and perceived them as \"good treatment,\" only one subject gave the calls credit for helping him maintain sobriety.", "This study evaluated the use of a brief motivational interview (MI) to reduce alcohol-related consequences and use among adolescents treated in an emergency room (ER) following an alcohol-related event. Patients aged 18 to 19 years (N = 94) were randomly assigned to receive either MI or standard care (SC). Assessment and intervention were conducted in the ER during or after the patient's treatment. Follow-up assessments showed that patients who received the MI had a significantly lower incidence of drinking and driving, traffic violations, alcohol-related injuries, and alcohol-related problems than patients who received SC. Both conditions showed reduced alcohol consumption. The harm-reduction focus of the MI was evident in that MI reduced negative outcomes related to drinking, beyond what was produced by the precipitating event plus SC alone.", "To date, the published controlled trials on exposure to alcohol cues have had an abstinence treatment goal. A modification of cue exposure (CE) for moderation drinking, which incorporated priming doses of alcohol, could train participants to stop drinking after 2 to 3 drinks. This study examined the effects of modified CE within sessions, combined with directed homework practice. Nondependent problem drinkers who requested a moderation drinking goal were randomly allocated to modified CE or standard cognitive-behavior therapy (CBT) for alcohol abuse. Both interventions were delivered in 6 90-min group sessions. Eighty-one percent of eligible participants completed treatment and follow-up assessment. Over 6 months, CE produced significantly greater reductions than CBT in participants' reports of drinking frequency and consumption on each occasion. No pretreatment variables significantly predicted outcome. The modified CE procedure appears viable for nondependent drinkers who want to adopt a moderate drinking goal.", "Recognizing the need to offer alternative methods of brief interventions, this study developed correspondence treatments for low-dependent problem drinkers and evaluated their impact. One hundred and twenty-one problem drinkers were recruited by media advertisements and were randomly allocated to a full cognitive-behavioural treatment programme (CBT) or to a minimal intervention condition (MI) that gave information regarding alcohol misuse and instructions to record drinking++. As predicted, CBT was more effective than MI in reducing alcohol consumption over the 4-month controlled trial period. CBT produced a 50% fall in consumption, bringing the average intake of subjects within recommended maximum levels. Treatment gains at 6 months were well maintained to 12 months. High levels of consumer satisfaction, a high representation of women and a substantial participation from isolated rural areas attested to the feasibility of the correspondence programme as an alternative treatment. However, some drinking occasions still involved high intake for a significant subgroup of subjects, and this issue will be addressed in future programmes. The results supported the use of correspondence delivery as a means of promoting early engagement and equity of access between city and country areas.", "The relative effects of simple advice and brief counseling were evaluated with heavy drinkers identified in primary care and other health settings in eight countries.\n Subjects (1260 men, 299 women) with no prior history of alcohol dependence were selected if they consumed alcohol with sufficient frequency or intensity to be considered at risk of alcohol-related problems. Subjects were randomly assigned to a control group, a simple advice group, or a group receiving brief counseling. Seventy-five percent of subjects were evaluated 9 months later.\n Male patients exposed to the interventions reported approximately 17% lower average daily alcohol consumption than those in the control group. Reductions in the intensity of drinking were approximately 10%. For women, significant reductions were observed in both the control and the intervention groups. Five minutes of simple advice were as effective as 20 minutes of brief counseling.\n Brief interventions are consistently robust across health care settings and sociocultural groups and can make a significant contribution to the secondary prevention of alcohol-related problems if they are widely used in primary care.", "Alcoholism is the leading risk factor for injury. The authors hypothesized that providing brief alcohol interventions as a routine component of trauma care would significantly reduce alcohol consumption and would decrease the rate of trauma recidivism.\n This study was a randomized, prospective controlled trial in a level 1 trauma center. Patients were screened using a blood alcohol concentration, gamma glutamyl transpeptidase level, and short Michigan Alcoholism Screening Test (SMAST). Those with positive results were randomized to a brief intervention or control group. Reinjury was detected by a computerized search of emergency department and statewide hospital discharge records, and 6- and 12-month interviews were conducted to assess alcohol use.\n A total of 2524 patients were screened; 1153 screened positive (46%). Three hundred sixty-six were randomized to the intervention group, and 396 to controls. At 12 months, the intervention group decreased alcohol consumption by 21.8+/-3.7 drinks per week; in the control group, the decrease was 6.7+/-5.8 (p = 0.03). The reduction was most apparent in patients with mild to moderate alcohol problems (SMAST score 3 to 8); they had 21.6+/-4.2 fewer drinks per week, compared to an increase of 2.3+/-8.3 drinks per week in controls (p < 0.01). There was a 47% reduction in injuries requiring either emergency department or trauma center admission (hazard ratio 0.53, 95% confidence interval 0.26 to 1.07, p = 0.07) and a 48% reduction in injuries requiring hospital admission (3 years follow-up).\n Alcohol interventions are associated with a reduction in alcohol intake and a reduced risk of trauma recidivism. Given the prevalence of alcohol problems in trauma centers, screening, intervention, and counseling for alcohol problems should be routine.", "This report describes the 48-month efficacy and benefit-cost analysis of Project TrEAT (Trial for Early Alcohol Treatment), a randomized controlled trial of brief physician advice for the treatment of problem drinking.\n Four hundred eighty-two men and 292 women, ages 18-65, were randomly assigned to a control (n = 382) or intervention (n = 392) group. The intervention consisted of two physician visits and two nurse follow-up phone calls. Intervention components included a review of normative drinking, patient-specific alcohol effects, a worksheet on drinking cues, drinking diary cards, and a drinking agreement in the form of a prescription.\n Subjects in the treatment group exhibited significant reductions (p < 0.01) in 7-day alcohol use, number of binge drinking episodes, and frequency of excessive drinking as compared with the control group. The effect occurred within 6 months of the intervention and was maintained over the 48-month follow-up period. The treatment sample also experienced fewer days of hospitalization (p = 0.05) and fewer emergency department visits (p = 0.08). Seven deaths occurred in the control group and three in the treatment group. The benefit-cost analysis suggests a 43,000 dollars reduction in future health care costs for every 10,000 dollars invested in early intervention. The benefit-cost ratio increases when including the societal benefits of fewer motor vehicle events and crimes.\n The long-term follow-up of Project TrEAT provides the first direct evidence that brief physician advice is associated with sustained reductions in alcohol use, health care utilization, motor vehicle events, and associated costs. The report suggests that a patient's personal physician can successfully treat alcohol problems and endorses the implementation of alcohol screening and brief intervention in the US health care system.", "The study aim was to test whether a brief motivational intervention, with or without a booster session, would improve drinking-related outcomes more than standard Emergency Department (ED) treatment.\n The study population consisted of 539 (78% male) injured patients treated in the ED and discharged to the community following their treatment. Injured patients met inclusion criteria if they were assessed as hazardous or harmful drinkers by scoring eight or more on the AUDIT and/or having alcohol in their system at the time of their injury or ED visit. Patients were randomly assigned to either standard care (SC), brief intervention (BI) or brief intervention plus a booster session (BIB). At 1-year follow-up, 447 patients (83% of the sample) were re-interviewed to measure alcohol-related negative consequences, injuries and drinking.\n Patients receiving BIB, but not B1 patients, reduced alcohol-related negative consequences and alcohol-related injuries more than did those in the SC group. All three groups reduced their days of heavy drinking. Patients with histories of hazardous drinking responded to BIB, whether or not they had consumed alcohol prior to their injury.\n Together, these results indicate that the effects of a booster session that is added to a brief intervention in the ED can be helpful to injured patients with a history of hazardous or harmful drinking, irrespective of whether they have consumed alcohol prior to their injury.", "The 'Pressures to Change' approach to working with the partners of drinkers is a structured procedure for promoting change in resistant drinkers. In this study 22 women and one man were randomly allocated to two treatment conditions and one no-treatment waiting list control condition in an experimental evaluation of the procedure. Group 1 was treated individually and Group 2 was treated as a group. Almost two-thirds of the drinking partners of clients in treatment made a significant move towards change, compared with none of the drinkers in the waiting list control condition.", "nan" ]

[ "8818850", "10048679", "7666122", "12526069", "9802626", "8818851", "1660824", "1324645", "8396086", "1651860", "11266417", "9552709", "8895044" ]

[ "Once-daily, 3-day azithromycin versus a three-times-daily, 10-day course of co-amoxiclav in the treatment of adults with lower respiratory tract infections: results of a randomized, double-blind comparative study.", "Etiology and treatment of community-acquired pneumonia in ambulatory children.", "Efficacy and tolerability of azithromycin versus amoxicillin/clavulanic acid in acute purulent exacerbation of chronic bronchitis.", "Comparative randomized trial of azithromycin versus erythromycin and amoxicillin for treatment of community-acquired pneumonia in children.", "Safety and efficacy of azithromycin in the treatment of community-acquired pneumonia in children.", "A randomized, comparative study to evaluate the efficacy and tolerability of a 3-day course of azithromycin versus a 10-day course of co-amoxiclav as treatment of adult patients with lower respiratory tract infections.", "Simplified treatment of acute lower respiratory tract infection with azithromycin: a comparison with erythromycin and amoxycillin. European Azithromycin Study Group.", "Double-blind randomized study comparing the efficacies and safeties of a short (3-day) course of azithromycin and a 5-day course of amoxicillin in patients with acute exacerbations of chronic bronchitis.", "A single-blind comparison of three-day azithromycin and ten-day co-amoxiclav treatment of acute lower respiratory tract infections.", "Comparative study of azithromycin and amoxicillin/clavulanic acid in the treatment of lower respiratory tract infections.", "Efficacy, safety and tolerability of 3 day azithromycin versus 10 day co-amoxiclav in the treatment of children with acute lower respiratory tract infections.", "A short (3-day) course of azithromycin tablets versus a 10-day course of amoxycillin-clavulanic acid (co-amoxiclav) in the treatment of adults with lower respiratory tract infections and effects on long-term outcome.", "Comparison of azithromycin and co-amoxiclav in the treatment of acute tracheobronchitis and acute infectious exacerbations of chronic bronchitis in adults. Azithromycin Study Group." ]

[ "A 3-day regimen of azithromycin (500 mg once daily) and a 10-day regimen of co-amoxiclav (625 mg three times daily) were compared in a double-blind study of 67 patients with acute infectious exacerbations of chronic bronchitis (AIECBs, n = 54), acute bronchitis (n = 7), or pneumonia (n = 6). In patients treated with azithromycin, satisfactory clinical responses (cure or improvement) were seen in 24/28 (86%) patients with AIECBs, 2/4 (50%) with acute bronchitis and 2/2 (100%) with pneumonia. Responses were satisfactory in 24/26 (92%), 4/4 (100%) and 4/4 (100%) patients, respectively, receiving co-amoxiclav. Streptococcus pneumoniae and Haemophilus influenzae were the commonest pathogens isolated at baseline. At the end of treatment, baseline pathogens were eradicated in 9/10 microbiologically-assessable patients treated with azithromycin and in 10/10 treated with co-amoxiclav. Adverse events related or possibly related to treatment occurred in five patients in each treatment group; the majority of these events affected the gastrointestinal system. One patient in each treatment group discontinued therapy because of adverse events. The study, therefore, demonstrates that 500 mg azithromycin administered once daily for 3 days is as efficacious and well tolerated as co-amoxiclav given three times daily for 10 days in the domiciliary treatment of adults with acute lower respiratory tract infections.", "To determine the etiology of community-acquired pneumonia in ambulatory children and to compare responses to treatment with azithromycin, amoxicillin-clavulanate or erythromycin estolate.\n Ambulatory patients with pneumonia were identified at the Children's Medical Center of Dallas, TX. Children age 6 months to 16 years with radiographic and clinical evidence of pneumonia were enrolled and randomized to receive either azithromycin suspension for 5 days or a 10-day course of amoxicillin-clavulanate for those <5 years or erythromycin estolate suspension for those > or = 5 years. Blood culture was obtained in all patients and we obtained nasopharyngeal and pharyngeal swabs for culture and polymerase chain reaction (PCR) testing for Chlamydia pneumoniae and Mycoplasma pneumoniae and nasopharyngeal swabs for viral direct fluorescent antibody and culture. Acute and convalescent serum specimens were tested for antibodies to C. pneumoniae, M. pneumoniae and Streptococcus pneumoniae. Patients were evaluated 10 to 37 days later when repeat specimens for serology, PCR and culture were obtained. For comparative purposes healthy children attending the well-child clinic had nasopharyngeal and pharyngeal swabs obtained for PCR and culture for C. pneumoniae and M. pneumoniae.\n Between February, 1996, and December, 1997, we enrolled 174 patients, 168 of whom fulfilled protocol criteria for evaluation. There were 55% males and 63% were <5 years of age. All blood cultures were sterile and there was no correlation between the white blood cell and differential counts and etiology of pneumonia. Etiologic agents were identified in 73 (43%) of 168 patients. Infection was attributed to M. pneumoniae in 7% (12 of 168), C. pneumoniae in 6% (10 of 168), S. pneumoniae in 27% (35 of 129) and viruses in 20% (31 of 157). None of the swab specimens from 75 healthy control children was positive for C. pneumoniae or M. pneumoniae. Clinical response to therapy was similar for the three antibiotic regimens evaluated, including those with infection attributed to bacterial agents.\n Although a possible microbial etiology was identified in 43% of the evaluable patients, clinical findings and results of blood cultures, chest radiographs and white blood cell and differential counts did not distinguish patients with a defined etiology from those without a known cause for pneumonia. There were no differences in the clinical responses of patients to the antimicrobial regimens studied.", "An open randomized trial was conducted in 142 hospitalized and out-patients with acute purulent exacerbation of chronic bronchitis to compare the clinical efficacy and tolerability of azithromycin (n = 69) and amoxicillin/clavulanic acid (n = 73). Azithromycin (500 mg) was administered as a single dose for three days and amoxicillin/clavulanic acid (amoxicillin 875 mg-clavulanic acid 125 mg) was given b.i.d. for 8 days (8.16 +/- 1.18). Before therapy and 24-48 hours after the end of treatment, sputum culture (by positioning five orthodontal swabs at the opening of salivary gland ducts after a washing of the oral cavity with sterile saline solution to avoid oral contamination), chest X-rays, arterial blood gas analysis, trials of respiratory functions and routine blood tests were performed. In the azithromycin group (69 patients) the efficacy rate was 67.6% (46 patients: 34 cured and 12 improved); in 22 patients (32.4%) the treatment failed; 1 patient was not evaluated because of no follow-up. The overall efficacy rate in the amoxicillin/clavulanic acid group (73 patients) was 97.3% (71 patients: 60 cured and 11 improved); in 1 patient (1.4%) the treatment failed and 1 patient was a drop-out for side effects. All pathogens isolated before treatment were susceptible to the antibiotics administered. At the end of treatment microbiological efficacy was 67.1% in the azithromycin group and 98.6% in the amoxicillin/clavulanic acid group. The tolerability was judged good in both treatment groups. Side effects were observed in 1 patient treated with amoxicillin/clavulanic acid (diarrhea), which imposed interruption of treatment, and in 2 patients from the azithromycin group (gastralgia and biochemical laboratory tests: renal function).(ABSTRACT TRUNCATED AT 250 WORDS)", "Our objective was to compare the clinical efficacy of azithromycin vs. erythromycin and amoxicillin in the treatment of presumed bacterial community-acquired pneumonia in ambulatory children, and to evaluate the etiologies of these illnesses. One hundred and ten children, aged 1 month to 14 years, were enrolled between January 1996-January 1999. Children were distributed into two groups according to clinical and radiological patterns: classic or atypical pneumonia. Patients with classic pneumonia were randomly assigned to receive oral amoxicillin 75 mg/kg/day for 7 days, or azithromycin 10 mg/kg/day for 3 days; patients with atypical pneumonia received azithromycin 10 mg/kg/day for 3 days, or erythromycin 50 mg/kg/day for 14 days. Chest X-ray, clinical, and laboratory parameters were obtained on enrollment. Clinic visits were performed on days 3, 7, and 14, and chest X-ray follow-up on days 7 and 14. Microbiological diagnosis of classic pathogens was based on blood and bronchial secretion cultures. The diagnosis of atypical pathogens C. pneumoniae, C. trachomatis, and M. pneumoniae was based on PCR and serologic tests.Forty-seven children met the criteria for classic pneumonia (23 children received azithromycin, and 24 received amoxicillin), and 59 children had atypical pneumonia (33 children were treated with azithromycin, and 26 with erythromycin). Demographic characteristics at enrollment were similar between children with classic pneumonia treated with azithromycin and erythromycin and children treated with azithromycin and erythromycin for atypical pneumonia. However, on day 7, children with classic pneumonia who received azithromycin normalized their chest X-ray more often than those who received amoxicillin (81.0% vs. 60.9%, respectively, P = 0.009). The same was true for children with atypical pneumonia; their chest X-rays had normalized by day 14 (100% in those with azithromycin vs. 81% in those with erythromycin, P = 0.059). Also, children with atypical pneumonia treated with azithromycin had earlier cessation of cough than children treated with erythromycin (3.6 +/- 1.9 vs. 5.5 +/- 3.6 days respectively, P = 0.02). There were only three children with side effects (mild diarrhea, all in the erythromycin group). Etiological agents were identified in 41% of children. In conclusion, azithromycin is an effective therapeutic option for the treatment of community-acquired classic and atypical pneumonia in children.\n Copyright 2003 Wiley-Liss, Inc.", "To compare the safety and efficacy of azithromycin with amoxicillin/clavulanate or erythromycin for the treatment of community-acquired pneumonia, including atypical pneumonia caused by Mycoplasma pneumoniae and Chlamydia pneumoniae.\n Multicenter, parallel group, double blind trial in which patients 6 months to 16 years of age with community-acquired pneumonia were randomized 2:1 to receive either azithromycin for 5 days or conventional therapy for 10 days (amoxicillin/clavulanate if < or =5 years of age or erythromycin estolate if >5 years of age). Patients from 23 geographically diverse sites were evaluated for clinical outcomes and/or adverse events at Days 3 to 5, Days 15 to 19 and 4 to 6 weeks posttherapy. Microbiology (culture or polymerase chain reaction) was done at baseline and Days 15 to 19 for bacteria, Chlamydia pneumoniae and Mycoplasma pneumoniae. Serology for C. pneumoniae and M. pneumoniae was done at baseline and 4 to 6 weeks posttherapy.\n Of 456 patients enrolled during 17 consecutive months, 420 were evaluable. Clinical success at Study Days 15 to 19 was 94.6% in the azithromycin group and 96.2% in the comparative treatment group (P = 0.735) and at 4 to 6 weeks posttherapy 90.6 and 87.1%, respectively (P = 0.330). Evidence of infection was identified in 46% of 420 evaluable patients (1.9% bacteria, 29.5% M. pneumoniae and 15% C. pneumoniae). Microbiologic eradication was 81% for C. pneumoniae and 100% for M. pneumoniae in the azithromycin group vs. 100 and 57%, respectively, in the comparator group. Treatment-related adverse events occurred in 11.3% of the azithromycin group and 31% in the comparator group (P < 0.05).\n Azithromycin used once daily for 5 days produced a satisfactory therapeutic outcome similar to those of amoxicillin/clavulanate or erythromycin given three times a day for 10 days for treatment of community-acquired pneumonia. Azithromycin had significantly fewer side effects than comparator drugs.", "Clinical and bacteriological efficacy and tolerability of azithromycin (500 mg once daily for 3 days) and those of a 10-day regimen of co-amoxiclav (37 mg three times daily) were evaluated in a large-scale, double-blind comparative study of 369 patients (> or = 18 years old) with acute lower respiratory tract infections. After treatment, 165/173 (95%) azithromycin- and 166/173 (96%) co-amoxiclav-treated patients had responded satisfactorily (cure or improvement). Baseline pathogens (mainly Streptococcus pneumoniae and Haemophilus influenzae) were eradicated in 82/82 (100%) azithromycin- and 73/74 (99%) co-amoxiclav-treated patients who were bacteriologically assessable. Adverse events, which were predominantly of mild to moderate severity and mostly affected the gastrointestinal system, were recorded in 13/186 (7%) azithromycin- and 19/183 (10%) co-amoxiclav-treated patients. Only two (1%) azithromycin-treated patients discontinued treatment due to adverse events compared with eight (4%) who received co-amoxiclav. The results show that azithromycin at a dose of 500 mg once daily for 3 days is an effective and safe alternative to a 10-day, three-times-daily course of co-amoxiclav in the treatment of lower respiratory tract infections in adults.", "In two randomized, multicentre studies azithromycin treatment (1.5 g in five or six doses over 5 days) was compared with erythromycin treatment (14 or 20 g in 28 or 40 doses over 7 or 10 days) and amoxycillin treatment (10.5 g in 21 doses over 7 days) in patients with acute respiratory tract infection. In the two separate studies, azithromycin gave complete clinical cure in 70% and 51%, respectively, of patients compared with in 60% of erythromycin- and 45% of amoxycillin-treated patients. Eradication of the main pathogens isolated at baseline (Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus) was comparable in the azithromycin, erythromycin and amoxycillin treatment groups. Efficacy was not affected by the presence or absence of underlying pulmonary disease. There were no major abnormalities in laboratory safety parameters and adverse events, principally mild/moderate gastro-intestinal symptoms occurred in 5% or 15%, respectively, of azithromycin-treated patients compared with in 18% or 17%, respectively, of those receiving erythromycin or amoxycillin. It is concluded that azithromycin was as effective and better tolerated than erythromycin or amoxycillin.", "The efficacies and safeties of a three-dose regimen of azithromycin (500 mg once daily for 3 days) and a 15-dose regimen of amoxicillin (500 mg three times daily for 5 days) were compared in a double-blind manner in patients with an acute exacerbation of chronic bronchitis. A total of 92% of patients suffered a type 1 exacerbation. Treatment success, defined as cure or major improvement, was achieved in all patients in the azithromycin group by day 5, compared with 23 (92%) of 25 patients in the amoxicillin group. On day 12, these data were 24 of 25 (96%) in the azithromycin group and 20 of 25 (80%) in the amoxicillin group (results were not significantly different). Several pathogens were isolated (MIC ranges [micrograms per milliliter] in parentheses): Haemophilus influenzae or Haemophilus parainfluenzae was isolated 23 times (azithromycin, less than or equal to 0.06 to 32; amoxicillin, 0.12 to 2); Streptococcus pneumoniae was isolated from 11 patients (azithromcyin, less than or equal to 0.06 greater than 256; amoxicillin, less than or equal to 0.06 to 0.25); Moraxella (Branhamella) catarrhalis was isolated from eight patients (azithromycin, less than or equal to 0.06; amoxicillin, less than or equal to 0.06 to 16); and other members of the family Enterobacteriaceae were isolated from eight patients. One patient treated with azithromycin had Legionella pneumophila pneumonia, and another in that group had a significant rise in titer of antibody against influenza A virus. One patient treated with amoxicillin also had a significant rise in titer of antibody against influenza A virus. Microbiological response rates were comparable. One patient who received azithromycin developed abnormal liver function. Two patients treated with amoxicillin developed abnormal liver functions, one developed exanthema, and one treatment was stopped because of nausea. It is concluded that a three-dose (3-day) regimen of azithromycin is as effective clinically and microbiologically as a 15-dose (5-day) regimen of amoxicillin in the treatment of acute exacerbations of chronic bronchitis.", "The efficacy and safety of a three-day regimen of azithromycin (500 mg od) and a ten-day regimen of co-amoxiclav (625 mg tid) were compared in a single-blind study in 99 patients with acute lower respiratory tract infections. Of these, 70 (71%) suffered an infective exacerbation of their chronic obstructive pulmonary disease. Nine patients had pneumonia and 19 purulent bronchitis. Treatment success, defined as cure or improvement, occurred in 43 of 48 (90%) patients in the azithromycin group, compared with 45 of 51 (88%) patients in the co-amoxiclav group. The most common isolated pathogens were Haemophilus influenzae (25 cases; MIC range of azithromycin (A) < or = 0.06-4 mg/L; for co-amoxiclav (CA) 0.25-4 mg/L; Streptococcus pneumoniae (10 cases; A: < or = 0.06- > 128; CA: < or = 0.06); and Moraxella catarrhalis (four cases; A: < or = 0.06; CA: < or = 0.06-0.25). Microbiological response rates were comparable in the two groups. In 5% of patients, serological evidence for virus or atypical pathogens was found. Thirteen (26%) patients treated with co-amoxiclav had gastrointestinal complaints (seven with diarrhoea), compared with five (10%) treated with azithromycin (P = 0.09). Additional complaints occurred in three patients treated with co-amoxiclav and in one patient treated with azithromycin. It was concluded that a three-day regimen of azithromycin was as effective, clinically and microbiologically, as a ten-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections.", "Forty-eight patients with acute bronchitis and four with pneumonia were randomly assigned to receive five doses (500 mg on day 1, plus 250 mg/day on days 2-5) of azithromycin; 54 patients with acute bronchitis and four with pneumonia were assigned 30 doses (625 mg every eight hours for ten days) of amoxicillin/clavulanic acid (CA). The two regimens were equally effective, with clinical improvement or cure in 92% and 87% of patients respectively, bacteriological cure in 89% and 86%, with 91% and 89% of pathogens eliminated. Minor side effects occurred in 6% and 12% of patients in the two groups, respectively. No major abnormalities in laboratory safety parameters were seen in either group.", "To compare the efficacy, safety and tolerability of a 3 day course of azithromycin with a 10 day course of co-amoxiclav in the treatment of children with acute lower respiratory tract infection (LRTI), 118 patients with community-acquired LRTI were included in a multicentre randomized double-blind, double-dummy study. The diagnosis of LRTI was based on the presence of respiratory signs and symptoms in combination with consolidation on a chest radiograph or clinical evidence of LRTI. Patients received oral azithromycin suspension (10 mg/kg/24 h) or placebo in one dose for 3 days and co-amoxiclav (45/11.25 mg/kg/24 h) or placebo in three doses for 10 days. Of 110 eligible patients, 56 and 54 patients, respectively, were treated with azithromycin or co-amoxiclav. The percentage of patients cured or clinically improved at days 10-13 (primary endpoint) was 91% for azithromycin and 87% for co-amoxiclav. This difference of 4% (90% confidence interval: -6%, +14%) was not statistically significant (P= 0.55). Significantly (P = 0.01) more related adverse events were found in the co-amoxiclav group. This was largely due to a higher percentage (43% versus 19%) of gastrointestinal complaints. A 3 day course of azithromycin (three doses) is as effective in the treatment of LRTI in children as a 10 day course of co-amoxiclav (30 doses). The azithromycin group had fewer adverse events. We conclude that azithromycin is an effective, safe and well-tolerated drug in the treatment of children with LRTI. An additional advantage is the easy administration and short duration of therapy.", "The efficacy and safety of a 3-day regimen of azithromycin prescribed in the new tablet form and of a 10-day regimen of amoxycillin clavulanic acid (co-amoxiclav, Augmentin) were compared in patients with acute lower respiratory tract infections. Of the 144 enrolled patients, 123 had a Type 1 acute exacerbation of chronic bronchitis (AECB), three patients had pneumonia, and 18 had purulent bronchitis. Treatment was successful, defined as cure or major improvement on day 14, in 59/62 (95%) patients in the azithromycin treatment group compared with 54/61 (90%) patients in the co-amoxiclav. At 30 days, the incidence of success was 77% (48/62) in the azithromycin treated group, compared with 66% (40/61) of co-amoxiclav-treated patients. At 60 days, incidences were 66% (41/62) and 59% (36/61), respectively. Several pathogens were isolated: Haemophilus influenzae in 21 patients (minimum inhibitory concentration (MIC) range for azithromycin 0.12-4 mg/l; co-amoxiclav 0.25-4 mg/l); Streptococcus pneumoniae in nine (MIC azithromycin < or = 0.06 > or = 256 mg/l; co-amoxiclav < or = 0.06-1 mg/l); and Moraxella catarrhalis in 11 (MIC azithromycin < or =0.06-2 mg/l; co-amoxiclav < or = 0.06-0.5 mg/l). Microbiological response rates were comparable. A significant correlation between clinical and microbiological cure was found (p = 0.02, power 0.6). In 15 (10%) patients, positive serology for viruses or atypical pathogens was found. In the co-amoxiclav-treatment group, 24 patients had mild adverse events (12 diarrhoea), compared with 27 treated with azithromycin (p = 0.47). It is concluded that a 3-day regimen of azithromycin prescribed as tablets is as clinically and microbiologically effective as a 10-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections. Moreover, since the percentage of viral infections was low and a significant correlation between microbiological and clinical cure was found, this study shows that clinical symptoms can be used to establish which patients with AECB (Type 1) should be treated with antimicrobial agents.", "Azithromycin, a broad-spectrum azalide, and co-amoxiclav were compared in a randomized, multicentre, open-label trial in 759 patients treated for acute tracheobronchitis (n = 620) or acute infectious exacerbations of chronic bronchitis (n = 139). Patients were randomized (2:1) to a 3-day regimen of two azithromycin 250 mg capsules once daily or a 5-10-day regimen of co-amoxiclav, one 625 mg tablet three times daily. Azithromycin produced a significantly higher cure rate (70.6% versus 61.1%) than co-amoxiclav (P = 0.011) and there were fewer failures (7.8% versus 13.6%) and relapses in the azithromycin-treated group, giving a higher overall response rate for azithromycin (89.7% versus 80.2%, P = 0.0003). With azithromycin, compliance was better than with co-amoxiclav and there was a significantly shorter time to improvement or cure. A higher incidence of adverse events, mostly gastrointestinal, was reported by patients taking co-amoxiclav (21.3% versus 14%, P = 0.0097), causing more patients in this group to discontinue therapy (7% versus 1.2%, P = 0.00004)." ]

[ "14657819", "9743925", "9697567", "11840407", "9355594", "1640278", "7556325", "8932071" ]

[ "Benefit and risk of heparin for maintaining peripheral venous catheters in neonates: a placebo-controlled trial.", "A randomized trial of heparin and saline for maintaining intravenous locks in neonates.", "Patency of 24-gauge peripheral intermittent infusion devices: a comparison of heparin and saline flush solutions.", "Comparison of normal saline and heparinized saline for patency of IV locks in neonates.", "The use of heparin and normal saline flushes in neonatal intravenous catheters.", "Efficacy of heparin in peripheral venous infusion in neonates.", "The efficacy of heparin in maintaining peripheral infusions in neonates.", "Heparin vs saline for intermittent intravenous device maintenance in neonates." ]

[ "Heparin addition to infusion fluids is used to prolong catheter patency in newborns. Heparin may also induce adverse effects such as bleeding complications and immune-mediated heparin-induced thrombocytopenia (HIT). One objective was peripheral venous catheter patency with heparinization of continuous infusions (0.5 IU/mL). Secondary objectives were incidences of bleeding, clinically manifest HIT, HIT antibodies, and catheter-related complications.\n Inclusion criteria were anticipated need for intravenous peripheral infusion (>or=5 days for HIT-related endpoints) and postnatal age <28 days at study entry. Exclusion criteria were bodyweight <1000 g, congenital malformation, need for therapeutic anticoagulation or mechanical ventilation, and severe bleeding. HIT antibodies were assessed by enzyme-linked immunosorbent assay.\n A total of 145 infants received heparin, and 151 infants received saline. Patient characteristics, number of additional drugs, duration of treatment, and location and size of catheters did not differ. Patency of catheters was 7.4 hours longer in the heparin group (33.8 hours vs 26.4 hours, P<.0001), but the total numbers of catheters did not differ (565 vs 692, P=.3). No infant developed HIT antibodies. Incidences of bleeding complications and thrombocytopenia were comparable between groups.\n Balancing the benefits against the risks of heparin addition and the rare complication of HIT, we will not use 0.5 IU/mL heparin addition to parenteral fluids.", "To determine the effects of saline, heparin 2 units (U) per ml saline, and heparin 10 U/ml saline flush solutions on the duration of intravenous (i.v.) locks and the incidence of i.v. infiltration in neonates.\n Randomized double-blind experiment.\n Tertiary-care nursery.\n Neonates (N = 90) hospitalized at birth in the intensive, intermediate care, or newborn units.\n Total hours from the time the i.v. was inserted to the time the i.v. was removed; hours from the time the i.v. was first flushed to the time the i.v. was removed; number of i.vs. removed because of infiltration.\n No statistical or clinical differences between the three groups for duration of i.v. nor for incidence of complications.\n The use of heparin in i.v. lock flush solution did not affect the duration of i.v. locks nor the incidence of infiltration in neonates.", "The purpose of this study was to compare the effectiveness of heparin and normal saline flush solutions in maintaining the patency of 24-gauge peripheral intermittent infusion devices (PIIDs). A prospective, non-randomized, sequential, blinded study design was conducted on a pediatric and a neonatal intensive care unit. The sample consisted of 134 catheters in 61 patients. Heparin and saline flush groups were similar for age, PIID placement site, irritating substances infused, and initial IV function. The median duration of catheters flushed with heparin was 42 hours and with saline was 35.3 hours. Kaplan-Meier Survival Analysis indicated that the duration of catheters flushed with heparin was significantly longer than those flushed with saline (p = .02). More catheters flushed with saline were removed because of problems (p = .027). Results of this study suggest that heparin is more effective than saline in maintaining the patency of small, 24-gauge catheters.", "In this randomized double-blind experiment of 49 neonatal intensive care unit patients, probable time to catheter failure was significantly longer (p =.0358) for catheters flushed with heparinized saline (median = 127) compared with those flushed with normal saline (median = 39). This is in contrast to the nonsignificant difference (p =.841) in mean scores for six heparin-flushed catheters (M = 41.5 hours, SD = 44.0) compared with 18 saline-flushed catheters (M = 30.4 hours, SD = 20.8) discontinued for reasons other than completion of treatment. We concluded that survival time analysis is necessary when evaluating results of time-dependent studies in which the end point may not be elective.\n Copyright 2002 by W.B. Saunders Company", "To compare the effects of heparin versus normal saline flush solutions on the duration of patency of peripheral IV catheters in neonates.\n A quasi experimental design compared the outcomes in 87 infants who were 32 weeks or greater gestation at birth. Thirty-three received heparin and 54 received normal saline.\n There were 159 starts among the subjects. No statistically significant difference in duration of patency between the groups was found. The duration was significantly longer for term than preterm infants and for insertion in scalp, arm, or hand than for leg or foot.\n Gestational age and site of insertion were the only predictor variables related to duration of patency for IV catheters.", "To determine the efficacy of continuous, low-dose heparin infusion in prolonging peripheral venous catheter patency in neonates.\n Randomized, prospective study.\n Level III neonatal intensive-care unit.\n 113 neonates requiring i.v. therapy.\n The neonates were randomly assigned to heparin (n = 63). The heparin group received 1/2 unit of heparin per milliliter of continuous intravenous infusate or intermittent heparin flush.\n Low-dose heparin infusion does not make a difference in the duration of peripheral venous catheter patency. The incidence of catheter-related complications in the heparin group is the same as for those receiving no heparin.\n The mean duration of catheter patency was 62.75 hours in the heparin group and 27.3 hours in the no-heparin group (p = .0001). The occurrence of infection, bleeding, and extravasation injury was zero in the sample studied. The incidence of phlebitis was 18 cases in 132 (13%) in the heparin group and 13 cases in 122 (10%) in the no-heparin group. According to chi-square analysis, the difference between groups was not statistically significant (p greater than .05).\n Low-dose heparin infusion in peripheral venous catheters in neonates increased the duration of intravenous catheter patency (p = .0001) without increased risks of bleeding, infection, phlebitis, or extravasation injury.", "The study set out to determine the survival times of peripheral total parenteral nutrition (TPN) infusion sites in neonates using a prospective, single blind, randomised trial design. The effects of various concentrations of co-administered heparin was measured using survival analysis, and of other continuous variables using multivariate analysis, against a non-heparinized control group. The study was conducted in special care baby unit located within a specialist maternity hospital in London, United Kingdom. Heparin at 0.1, 0.25, 0.5 and 1 IU/ml was added to TPN infusions delivered through peripheral veins and the survival times of the infusions determined. For infusion sites receiving heparinized fluids, the relative risk of failure decreased and the median survival time increased as the heparin concentration increased, with a maximal effect at a heparin concentration of 0.5 IU/ml (P < 0.001). Multivariate analysis using the Cox proportional hazard model confirmed the efficacy of heparin and highlighted a history of infusion therapy and the co-administration of gentamicin (from a range of drugs analysed) as being risk factors associated with infusion site failure.\n Intravenous infusion survival time can be prolonged using heparin additive at an optimal concentration of 0.5 IU/ml. This should also be of additional interest to paediatricians as heparin is an ubiquitous drug on neonatal units and its clinical use needs to be rationalised.", "The purpose of this study was to determine whether normal saline (NS) is as effective as 10 units heparin/ml saline (HS) in maintaining patency of intermittent intravenous devices (i.v. locks) in neonates. We conducted a prospective, double-blind, randomized study of 118 24-gauge catheters used exclusively as i.v. locks and removed consequent to catheter failure. Subjects were infants, including premature infants, less than one month of age, admitted to a Level II NICU. Catheters were observed for length of patency as well as incidence of phlebitis, occlusion, infiltration, and leaking. There was no statistically significant difference in average duration of patency between NS-flushed catheters and HS-flushed catheters. Phlebitis, occlusion, infiltration, and leaking occurred with equal frequency for both solutions." ]

[ "16881929", "16540800", "20973465", "17351300", "16556612", "17684213", "17374671" ]

[ "Multi-micronutrient Sprinkles including a low dose of iron provided as microencapsulated ferrous fumarate improves haematologic indices in anaemic children: a randomized clinical trial.", "Double-blind, placebo-controlled trial comparing effects of supplementation with two different combinations of micronutrients delivered as sprinkles on growth, anemia, and iron deficiency in cambodian infants.", "Daily use of Sprinkles micronutrient powder for 2 months reduces anemia among children 6 to 36 months of age in the Kyrgyz Republic: a cluster-randomized trial.", "Low dose 'Sprinkles'-- an innovative approach to treat iron deficiency anemia in infants and young children.", "Micronutrients (including zinc) reduce diarrhoea in children: the Pakistan Sprinkles Diarrhoea Study.", "Randomized comparison of 3 types of micronutrient supplements for home fortification of complementary foods in Ghana: effects on growth and motor development.", "Micronutrient Sprinkles reduce anemia among 9- to 24-mo-old children when delivered through an integrated health and nutrition program in rural Haiti." ]

[ "Home-fortification of complementary foods with micronutrients (including iron) as Sprinkles is a new strategy to control iron deficiency and anaemia in developing countries. However, the most effective dose and form of iron is not known. The purpose of this study was to compare the efficacy of various doses (12.5, 20 or 30 mg) and treatment methods (multi-micronutrient Sprinkles vs. ferrous sulphate drops) on haemoglobin (Hb) concentration after 8 weeks of treatment in anaemic children. In total, 133 anaemic Ghanaian children (Hb 70-99 g L(-1)) aged 6-18 months were randomly assigned to one of five daily interventions for 8 weeks. Out of the five interventions, four used Sprinkles, and one used iron drops. Of the four Sprinkles groups, three included 12.5, 20 or 30 mg of iron as ferrous fumarate, and one included 20 mg of iron as ferric pyrophosphate. The iron drops group included 12.5 mg of iron as liquid ferrous sulphate. Hb concentrations were measured at baseline, week 3 and week 8. The primary outcome measure was Hb concentration at 8 weeks after treatment. We compared differences in Hb and ferritin concentrations and prevalence of iron deficiency anaemia (Hb < 100 g L(-1) and soluble transferrin receptor concentrations >8.5 mg L(-1)) from baseline to 8 weeks within and between groups. Adherence and reporting of side effects (staining of the teeth, ease of use, diarrhoea and darkening of stools) were compared between groups. Mean change in Hb was 1.4 g L(-1) (SD = 1.8) (P = 0.0001). Change in Hb concentrations from baseline to 8 weeks was significant in all groups (P = 0.0001-0.0007), with no differences across groups. Geometric means of serum ferritin varied from 18.6 to 44.0 microg L(-1) at baseline. At week 8, these means were in the interval of 48.0-78.3 microg L(-1), with no group differences. Prevalence of iron deficiency anaemia decreased significantly from baseline to 8 weeks in all groups with the exception of the iron drops group, with no group differences. Adherence was lower in the drops group (64%) as compared with Sprinkles groups (84%). Greater staining of the teeth and less ease of use were reported in the drops group as compared with Sprinkles groups. A dose as low as 12.5 mg of iron as ferrous fumarate when provided as Sprinkles may be effective in anaemic children.", "To assess and compare efficacy of two micronutrient sprinkle supplementation on growth, anemia, and iron deficiency in Cambodian infants.\n A total of 204 infants aged 6 months and living in Kompong Chhnang Province, Cambodia were randomly assigned to receive daily supplements of either iron (12.5 mg) plus folic acid (150 mug) plus zinc (5 mg) (MMN, n = 68), or iron (12.5 mg) plus folic acid (150 microg) alone (FFA, n = 68), or placebo (n = 68) for a 12 month period in powder form as sprinkles. Anthropometrics was evaluated bimonthly. Biochemical assessment was performed at baseline and at the end of intervention period.\n At baseline, the overall mean (SD) of hemoglobin concentration was 101 g/L. No difference among groups was found for growth pattern. Significant decline was observed for weight-for-age and height-for-age z-scores in any group (P < 0.0001). The rate of recovery from anemia was significant (P < 0.001) and comparable between MMN (54%) and FFA (53%) groups and higher than in the placebo group (22%, P < 0.0001). Through the study period, no significant change in the rate of iron deficiency was found in MMN and FFA groups, whereas it increased in the placebo group (31%, baseline vs. 52%, end of study; P < 0.0001).\n Both MMN and FFA supplements were effective for preventing or treating anemia in Cambodian infants and stabilizing plasma levels of ferritin. Use of micronutrients in a controlled home setting, as sprinkled daily supplements, may be promising in preventing and treating anemia in developing countries.", "Iron-deficiency anemia is widespread among young children in the Kyrgyz Republic, and there is an urgent need to identify an effective intervention to address this significant public health problem.\n To test the effectiveness of a 2-month intervention with daily home fortification of complementary food using micronutrient powder (Sprinkles) in reducing anemia among children 6 to 36 months of age in the Kyrgyz Republic.\n In this cluster-randomized, community-based effectiveness trial conducted in three regions of the Kyrgyz Republic, 24 clusters of children aged 6 to 36 months were randomly assigned to two groups. The intervention group (12 clusters, n = 1,103) received 60 sachets of micronutrient powder (12.5 mg elemental iron), which were taken as one sachet daily for 2 months. The control group (12 clusters, n = 1,090) did not receive micronutrient powder until after the study period. Blood hemoglobin concentration was assessed at the start and end of the intervention.\n From baseline to follow-up, the mean hemoglobin concentration in the intervention group increased by 7 g/L, whereas it decreased by 2 g/L in the control group (p < .001). The prevalence of anemia (hemoglobin < 110 g/L) in the intervention group decreased from 72% at baseline to 52% at follow-up, whereas it increased from 72% to 75% in the control group (p < .001). Compliance with the intervention was high, with children consuming on average 45 of the 60 sachets given.\n A course of 60 Sprinkles micronutrient powder sachets taken daily for 2 months is effective in improving hemoglobin levels and reducing the prevalence of anemia among young children in the Kyrgyz Republic.", "Iron supplementation programs using pediatric tablets or drops have not been successful in the control of anemia amongst infants and children in India. Sprinkles is an innovative multi-micronutrient home fortification strategy to control iron deficiency and anemia.\n We aimed to determine the hematologic response to different doses and forms of iron in Sprinkles and iron drops.\n Twenty two villages of Vadu Rural Health Program, KEM Hospital, Pune.\n Double blind clustered randomized community-based trial.\n Children (n=432) aged 6 to 18 mo age with Hb between 70 to 100 g/L were enrolled.\n Selected villages were randomized into 5 groups: Sprinkles 12.5, 20 or 30 mg ferrous fumarate, Sprinkles 20 mg micronized ferric pyrophosphate or drops 20 mg ferrous glycine sulphate (DROPS) for 8 weeks. Household socio-demographic information was collected at baseline. Side effects and compliance were monitored through weekly visits. Hemoglobin was estimated at baseline, 3 and 8 weeks. Ferritin was assessed at baseline and 8 weeks.\n Baseline characteristics were similar across all groups. Hemoglobin increased significantly (P<0.0001) in all groups at 8 weeks with no difference between groups. Ferritin increased (P<0.0001) significantly in all groups with no difference across the groups. Compliance (overall range: 42 to 62 %) was lowest for DROPS. Side effects were significantly higher among DROPS compared to Sprinkles (p>0.05).\n Sprinkles 12.5 mg FF dose is as efficacious as higher doses of iron in Sprinkles or DROPS in increasing hemoglobin. Sprinkles FF 12.5 mg is recommended as it has fewer reported side effects and better compliance compared to DROPS.", "To examine the effect of the daily use of micronutrients (including zinc) or the same micronutrients plus heat inactivated lactic acid bacteria (LAB), on diarrhoea in children compared to placebo.\n A triple blind randomised clinical trial in an urban slum of Karachi, Pakistan. Micronutrients (including zinc), micronutrients (including zinc and LAB), or placebo, were provided daily for two months to 75 young children (aged 6-12 months) identified at high risk for diarrhoea related mortality on the basis of history of at least one episode of diarrhoea in the preceding two weeks. The longitudinal prevalence of diarrhoea was defined as the percentage of days a child had diarrhoea out of the days the child was observed.\n Mean longitudinal prevalence of diarrhoea in the micronutrient-zinc group was 15% (SD = 10%) child-days compared to 26% (SD = 20%) child-days in the placebo group and 26% (SD = 19%) child-days in the micronutrient-zinc-LAB group. The difference between the micronutrient-zinc-LAB and placebo groups was not significant.\n The daily provision of micronutrients (including zinc) reduces the longitudinal prevalence of diarrhoea and thus may also reduce diarrhoea related mortality in young children; heat inactivated LAB has negative effects in these children.", "The low micronutrient content of complementary foods is associated with growth faltering in many populations. A potential low-cost solution is the home fortification of complementary foods with Sprinkles (SP) powder, crushable Nutritabs (NT) tablets, or energy-dense (108 kcal/d), fat-based Nutributter (NB).\n The objective was to test the hypothesis that multiple micronutrients added to home-prepared complementary foods would increase growth and that the effect would be greatest in the presence of added energy from fat.\n We randomly assigned 313 Ghanaian infants to receive SP, NT, or NB containing 6, 16, and 19 vitamins and minerals, respectively, daily from 6 to 12 mo of age. We assessed anthropometric status at 6, 9, and 12 mo; micronutrient status at 6 and 12 mo; motor development at 12 mo; and morbidity weekly. Infants (n = 96) not randomly selected for the intervention (nonintervention; NI) were assessed at 12 mo.\n The groups did not differ significantly at baseline, except that the NB group had a higher proportion of boys and weighed slightly more. The dropout rate (15/313) was low. At 12 mo, after control for initial size, the NB group had a significantly greater weight-for-age z score (WAZ) (-0.49 +/- 0.54) and length-for-age z score (LAZ) (-0.20 +/- 0.54) than did the NT group (WAZ: -0.67 +/- 0.54; LAZ: -0.39 +/- 0.54) and the NT and SP groups combined (WAZ: -0.65 +/- 0.54; LAZ: -0.38 +/- 0.54); the difference with the NI group (WAZ: -0.74 +/- 1.1; LAZ: -0.40 +/- 1.0) was not significant. A lower percentage of the NI infants (25%) than of the intervention groups (SP: 39%; NT: 36%; NB: 49%) could walk independently by 12 mo.\n All 3 supplements had positive effects on motor milestone acquisition by 12 mo compared with no intervention, but only NB affected growth.", "We evaluated the effectiveness of a 2-mo treatment of Sprinkles containing 12.5 mg iron, 5 mg zinc, 400 microg vitamin A, 160 microg folic acid, and 30 mg vitamin C in reducing anemia among children 9- to 24 mo old in Haiti. Ten food distribution points (FDP) where children received take-home rations of fortified wheat-soy blend (WSB) were randomly allocated into 2 groups: 1) Sprinkles-WSB (S-WSB) (6 FDP; n = 254), receiving 30 sachets of Sprinkles monthly for 2 mo; and 2) WSB only (WSB) (4 FDP; n = 161), not receiving Sprinkles. At baseline, anemia prevalence [hemoglobin (Hb) < 100 g/L], adjusted for age and sex, was 54 and 39% in S-WSB and WSB groups, respectively. After the 2-mo intervention (1st follow-up), anemia, adjusted for baseline prevalence, age, and sex dropped to 24% in S-WSB (P < 0.001) and increased to 43% in WSB (P = 0.07). At 7 mo postintervention, anemia in S-WSB declined to 14%; 92% of children who were nonanemic at 1st follow-up remained so without further Sprinkles consumption. From baseline to 1st follow-up, mean Hb increased by 5.5 g/L and dropped by 1.0 g/L in the S-WSB and WSB groups, respectively (P < 0.001). From baseline to 2nd follow-up, mean Hb increased by 10.9 g/L in S-WSB (P < 0.001). Changes in mean Hb were greater for younger children (<21 mo at onset of intervention) (P < 0.05) and for children who were anemic at baseline (P < 0.001). In populations with a high prevalence of anemia, such as rural Haiti, 2 mo of Sprinkles are effective in reducing anemia among 9- to 24-mo-old children." ]

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[ "Evaluation of a structured teaching and treatment programme for type 2 diabetes in general practice in a rural area of Austria.", "Evaluation of a clinical pharmacist in caring for hypertensive and diabetic patients.", "A computer-generated reminder system improves physician compliance with diabetes preventive care guidelines.", "Diabetes management in a health maintenance organization. Efficacy of care management using cluster visits.", "Evaluation of a pharmaceutical care model on diabetes management.", "[Structured public health quality circle on the topic of diabetes management in general practice].", "Implementing practice guidelines for diabetes care using problem-based learning. A prospective controlled trial using firm systems.", "Increasing prescribed office visits. A controlled trial in patients with diabetes mellitus.", "Sharing the care of diabetic patients between hospital and general practitioners: does it work?", "Feasibility and effects of a diabetes type II protocol with blood glucose self-monitoring in general practice.", "A pilot Diabetic Support Service based on family practice attenders: comparison with diabetic clinics in east London.", "Interventions among primary-care practitioners to improve care for preventable complications of diabetes.", "Shared care for diabetes: supporting communication between primary and secondary care.", "A randomized controlled trial of quality assurance in sixteen ambulatory care practices.", "Continuous quality improvement can improve glycemic control for HMO patients with diabetes.", "Staged diabetes management. Toward an integrated model of diabetes care.", "Effect of multiple patient reminders in improving diabetic retinopathy screening. A randomized trial.", "Integrated care for diabetes: clinical, psychosocial, and economic evaluation. Diabetes Integrated Care Evaluation Team.", "Randomised controlled trial of patient centred care of diabetes in general practice: impact on current wellbeing and future disease risk. The Diabetes Care From Diagnosis Research Team.", "Sustained good glycaemic control in NIDDM patients by implementation of structured care in general practice: 2-year follow-up study.", "Reducing lower-extremity amputations due to diabetes. Application of the staged diabetes management approach in a primary care setting.", "A randomized controlled trial of an intervention designed to improve the care given in general practice to Type II diabetic patients: patient outcomes and professional ability to change behaviour.", "Application of a diabetes managed care program. The feasibility of using nurses and a computer system to provide effective care.", "Evaluation of general practice computer templates. Lessons from a pilot randomised controlled trial.", "Benefits provided by an integrated education and clinical diabetes centre: a follow-up study.", "The use of a nurse practitioner in the management of patients with diabetes mellitus.", "A telephone-delivered intervention for patients with NIDDM. Effect on coronary risk factors.", "Diabetes care organization, process, and patient outcomes: effects of a diabetes control program.", "Computerized decision support based on a clinical practice guideline improves compliance with care standards.", "Improved care of patients with diabetes through telecommunications.", "Putting population-based care into practice: real option or rhetoric?", "Do clinical guidelines introduced with practice based education improve care of asthmatic and diabetic patients? A randomised controlled trial in general practices in east London.", "Nurse case management to improve glycemic control in diabetic patients in a health maintenance organization. A randomized, controlled trial.", "Using telecommunication technology to manage children with diabetes: the Computer-Linked Outpatient Clinic (CLOC) Study.", "The Diabetes Education Study: a controlled trial of the effects of intensive instruction of internal medicine residents on the management of diabetes mellitus.", "Reduction of lower extremity clinical abnormalities in patients with non-insulin-dependent diabetes mellitus. A randomized, controlled trial." ]

[ "The efficacy of a treatment and teaching programme for non-insulin-treated Type 2 diabetic patients in general practice was evaluated in a prospective, controlled study. In a rural area in southern Austria, 53 patients from seven general practices participated in a structured programme (intervention group) and 55 patients from seven general practices without the programme served as the control group. After 6 months the weight reduction in the intervention group was 2.6 kg (1.6-3.7 kg, p < 0.001) and the difference in HbA1c between the groups was 0.92% (0.23-1.61%, p < 0.01) at follow-up. Systolic (-16.6 mmHg) and diastolic (-11.1 mmHg) blood pressure, serum triglycerides (-0.63 mmol I-1), and serum cholesterol (-0.40 mmol I-1) were reduced significantly in the intervention group (p < 0.006). The number of patients with callus formation and poor nail care decreased significantly after participating in the teaching programme (p < 0.001). In the control group no reduction in body weight, metabolic control or in risk factors for diabetic foot complications were observed. Calculated health care costs per patient and year decreased in the intervention group (-33 pounds) and increased in the control group (+ 30 pounds) mainly due to changes in prescription of oral hypoglycaemic agents in both groups. This programme may be an efficient and helpful model to increase overall quality of diabetes care according to the St Vincent Declaration.", "nan", "Computerized reminder systems have been shown to be effective in improving physician compliance with preventive services guidelines. Very little has been published about the use of computerized reminders for preventive care in diabetes. We implemented a computer-generated reminder system for diabetes care guidelines in a randomized controlled study in the outpatient clinics of 35 internal medicine residents at the University of Utah and Salt Lake Veterans Affairs Hospitals. After a six month study period, compliance with the recommended care significantly improved in both the intervention group that received patient-specific reminders about the guidelines (38.0% at baseline, 54.9% at follow-up) and the control group that received a nonspecific report (34.6% at baseline, 51.0% at follow-up). There was no significant difference between the two groups. Both clinic sites showed similar improvement over baseline levels of compliance. Residents who completed encounter forms used by the system showed a significantly greater improvement in compliance than those who did not complete encounter forms (19.7% vs. 7.6%, p = 0.006). The improvements in guideline compliance were seen in all areas of diabetes preventive care studied, and significant improvements were seen with recommended items from the medical history, physical exam, laboratory testing, referrals, and patient education. The use of encounter forms by the providers significantly improved documented compliance with the guidelines in almost all categories of preventive care. These results suggest that computerized reminder systems improve compliance with recommended care more by facilitating the documentation of clinical findings and the ordering of recommended procedures than by providing the clinician with patient-specific information about guideline compliance status. Further study is needed to understand the implications of these findings to the development of future computerized reminder systems for chronic diseases such as diabetes.", "To evaluate the effectiveness of a cluster visit model led by a diabetes nurse educator for delivering outpatient care management to adult patients with poorly controlled diabetes.\n This study involved a randomized controlled trial among patients of Kaiser Permanente's Pleasanton, CA, center who were aged 16-75 years and had either poor glycemic control (HbA1c > 8.5%) or no HbA1c test performed during the previous year. Intervention subjects received multidisciplinary outpatient diabetes care management delivered by a diabetes nurse educator, a psychologist, a nutritionist, and a pharmacist in cluster visit settings of 10-18 patients/month for 6 months. Outcomes included change (from baseline) in HbA1c levels; self-reported changes in self-care practices, self-efficacy, and satisfaction; and utilization of inpatient and outpatient health care.\n After the intervention, HbA1c levels declined by 1.3% in the intervention subjects versus 0.2% in the control subjects (P < 0.0001). Several self-care practices and several measures of self-efficacy improved significantly in the intervention group. Satisfaction with the program was high. Both hospital (P = 0.04) and outpatient (P < 0.01) utilization were significantly lower for intervention subjects after the program.\n A 6-month cluster visit group model of care for adults with diabetes improved glycemic control, self-efficacy, and patient satisfaction and resulted in a reduction in health care utilization after the program.", "To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus (NIDDM) in urban African-American patients.\n Eligible patients were randomized to either a pharmacist intervention or control group and followed over a 4-month period. Patients in the intervention group received diabetes education, medication counseling, instructions on dietary regulation, exercise, and home blood glucose monitoring, and evaluation and adjustment of their hypoglycemic regimen. Patients in the control group continued to receive standard medical care provided by their physicians.\n A university-affiliated internal medicine outpatient clinic.\n The study population consisted of urban African American patients with NIDDM currently attending the clinic.\n Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations. Secondary outcome endpoints included blood pressure, serum creatinine, creatinine clearance, microalbumin to creatinine ratio, total cholesterol, triglycerides, high-density lipoprotein, and low density lipoprotein concentrations. Quality-of-life assessments were performed in both groups at baseline and at the end of the study.\n Thirty-nine patients (17 intervention, 22 control) completed the study. The intervention group consisted of 12 women and 5 men with a mean +/- SD age of 59 +/- 12 years, total body weight (TBW) of 93 +/- 22 kg, body mass index (BMI) of 34 +/- 7 kg/m2, and duration of NIDDM 6.8 +/- 6.5 years. The control group consisted of 15 women and 7 men with a mean age of 65 +/- 12 years, TBW of 88 +/- 19 kg, BMI of 33 + 7 kg/m2, and a duration of NIDDM of 6.2 +/- 4.8 y. Significant improvement in glycated hemoglobin (p = 0.003) and fasting plasma glucose (p =0.015) was achieved in the intervention group. No change in glycemia was observed in the control subjects. Statistically significant differences in the final glycated hemoglobin (p = 0.003) and fasting plasma glucose (p = 0.022) concentrations were noted between groups. No significant changes in blood pressure control, lipid profile, renal function parameters, weight, or quality-of-life measures were noted within or between groups.\n Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients.", "The efficacy of quality circles has not yet been evaluated in controlled studies in Germany. The Central Research Institute for Ambulatory Health Care in Germany conducted a prospective controlled trial in order to evaluate the effects of structured quality circles on the process of quality ambulatory care for diabetic patients. Following a training for moderators (two for each quality circle) two quality circles undertook five sessions. In a representative random sample (25 diabetic patients per practice), the quality of diabetes care was evaluated before and after participation in the quality circles and was compared to the results of a control group without peer review. The participation in a quality circle resulted in a significant and relevant improvement of the quality concerning the detection of diabetes related complications.", "A controlled trial with 15-month follow-up was conducted in two outpatient clinics to study the effects of using the problem-based learning technique to implement a diabetes clinical practice guideline.\n A total of 144 patients with type 2 diabetes aged 25-65 years in two internal medicine outpatient clinics were enrolled in the study. African-Americans and Hispanics made up > 75% of the patients. Doctors and staff in one of the clinics were trained in the use of a clinical practice guideline based on Staged Diabetes Management. A problem-based learning educational program was instituted to reach consensus on a stepped intensification scheme for glycemic control and to determine the standards of care used in the clinic. HbA1c was obtained at baseline and at 9 and 15 months after enrollment.\n At 9 months, there was a mean -0.90% within-subject change in HbA1c in the intervention group, with no significant changes in the control group. The 15-month mean within-subject change in HbA1c of -0.62% in the intervention group was also significant. Among intervention patients, those with the poorest glycemic control at baseline realized the greatest benefit in improvement of HbA1c. The intervention group also exhibited significant changes in physician adherence with American Diabetes Association standards of care.\n Clinical practice guidelines are an effective way of improving the processes and outcomes of care for patients with diabetes. Problem-based learning is a useful strategy to gain physician support for clinical practice guidelines. More intensive interventions are needed to maintain treatment gains.", "Patients who fail to show for scheduled visits or who fail to contact their provider when warning symptoms occur pose important problems for the primary care physician. A group of interventions was examined to determine the effectiveness in increasing the number of prescribed office visits in patients with diabetes mellitus. This group of interventions included mailed packets with information on how to use the clinic, providers' names and phone numbers, after-hours phone numbers, a list of early warning signs, and a booklet on managing diabetes mellitus; mailed appointment reminders; and intense follow-up of visit failures for prompt rescheduling. Eight hundred fifty-nine patients on drug therapy for diabetes mellitus were stratified by risk of hospitalization and randomly assigned within strata to control and intervention groups. The intervention group received all interventions. After 1 year, the intervention group averaged 12% more total contacts than the control group (5.8 vs. 5.2, P = 0.01), due largely to an increase in kept scheduled visits (4.1 vs. 3.6, P = 0.006). These effects were greatest in those patients at higher risk of hospitalization. Also, visit failures were reduced only in high-risk patients. The effect of the interventions did not diminish during the year of study. This systematic and repetitive intervention appears effective in increasing prescribed office visits and is especially effective in patients requiring more frequent care.", "A randomized controlled trial was conducted to compare three forms of diabetes follow-up: (1) general practitioner care, (2) a system of care shared between the general practitioner (GP) and clinic and (3) conventional clinic care. Two hundred and six diabetic patients without significant diabetes-related or other medical complications were randomized to one of these follow-up systems. Metabolic control and blood pressure improved significantly and equally in all three groups (p < 0.05). The shared care group performed as well as or better than either of the other two groups in all other outcome measures. In particular, final attendance rates were 72% for shared care compared with only 35% for GP care and 53% for clinic care. Data collection rates for shared care were comparable with the clinic group for random blood glucose (88.9% vs 95.1%), weight (93.5% vs 98.3%), and blood pressure (94.8% vs 92.7%). Only in the case of glycosylated haemoglobin did shared care have poorer data collection (66.0% vs 98.4%). In all these parameters, except blood pressure, shared care out-performed the GP group. We conclude that with adequate support from and communication with hospital-based diabetes services, GPs are capable of providing care appropriate to the needs of uncomplicated diabetic patients.", "A diabetes protocol characterized by self-monitoring of blood glucose was introduced in four general practices with the aim of making the frequency of consultations dependent on the metabolic regulation and emphasizing body weight reduction. The feasibility of the programme was investigated and the results after 1 year were compared with those of conventional care in four control practices. In the experimental practices, 13 patients switched from a medical specialist's to a general practitioner's supervision, 20 remained under supervision of their GP and 33 started self-monitoring. The self-monitoring rate, the consultation frequency according to protocol, the low number of dropouts and inadequate referrals and adherence to the therapeutic scheme showed that the protocol was feasible for both the GPs and the patients. At the initial assessment, the regulation of the diabetes was worse in patients of the experimental group, compared with those of the control group (mean HbA1 9.7% vs 8.9%; p less than 0.05). On average, patients in the experimental group (n = 56) lost 0.4 kg of body weight, whereas those in the control group (n = 73) gained 0.1 kg (n.s.). The mean change in HbA1, adjusted for the initial value, was -0.4% in the experimental and +0.5% in the control group (p less than 0.05). The results of the protocol can be attributed to a combination of greater participation of the patient, the individualized consultation frequency and the prescription of oral hypoglycaemic agents according to body weight development.", "A pilot Diabetic Support Service (DSS) based on a computer register was devised for diabetic patients identified within three group practices in an inner city district of London. Of 159 eligible diabetics, 142 were followed over 2 years. Glycosylated haemoglobin (GHb) monitoring and adequacy of clinic reviews were audited. Care achieved by the DSS was compared with conventional Diabetic Clinic (DC) management of a sample of 200 diabetics from the same district. Serial GHb measurements were made on 66.2% of DSS and 44.5% of DC patients: GHb fell significantly only in DSS patients (13.1% to 11.4%). Proportional falls in GHb were comparable in each DSS treatment group (diet alone, oral hypoglycaemic agents, and insulin) and for hospital attenders and non-attenders equally. The planned clinical reviews were achieved in 40.1% of DSS patients entered (29% GP only, 54% of clinic attenders) and in 15% of DC patients (plus 75% fundal and blood pressure examination). The study led to provision of a formal diabetic clinic annual review system, diabetic mini-clinics in two of the three group practices, and the appointment of two Diabetic Liaison Sisters. With administrative simplification the system is to be made available to all diabetics in the District through their GPs during 1986-8.", "The National Diabetes Advisory Board recommends that diabetes prevention and control programs focus on the preventable complications of diabetes, i.e., visual impairment, lower-extremity problems, renal problems, ketoacidosis, and adverse outcomes of pregnancy. The Florida Diabetes Control Program chose to focus its efforts on the first three of these complications at the federal- and state-funded primary-care programs in Florida because these programs had access to targeted, public-sector patients and because of fiscal restraints that make the care provider the logical source of entry to the health-care system. This study sought to document the current level of care for complications of diabetes in primary-care settings, provide state-of-the-art professional education along with patient education, and evaluate changes in practice habits. Three intervention and three control primary-care centers were selected. Medical records in each center were reviewed over a 2-yr period. At intervention sites, retinopathy referrals increased from 9 to 43% (P less than .001), urinalyses increased from 69 to 94% (P less than .001), and examinations of lower extremities increased from 66 to 94% (P less than .001). There were no such changes in the control sites. Hypertension was diagnosed in nearly two-thirds of patients, and a last blood pressure of greater than 140 mmHg systolic or greater than 90 mmHg diastolic was present in 64% of the intervention group at yr 1 and declined to 56% at yr 2 (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)", "To assess the effects on information exchange of electronic communication between physicians co-treating diabetic patients.\n Comparison of traditional paper-based communication for reporting and electronic communication.\n General practitioners and an internal medicine outpatient clinic of an urban public hospital.\n A total of 275 diabetic patients, and the 32 general practitioners and one internal medicine consultant who cared for them. Intervention: An electronic communication network, linking up the computer-based patient records of the physicians, thus enabling electronic data interchange.\n Number of letters sent and received per year by the general practitioners, the number of diabetes-related parameters (e.g. results of laboratory tests) in the patient records, and HBA1C levels.\n Intervention GPs received more messages per year (1.6 per patient) than control GPs (0.5 per patient, P<0.05). Significant higher availability (P<0.05) was achieved for data on HBA1C levels, fructosamine levels, blood pressure measurements, cholesterol levels, triglyceride levels and weight measurements. Intervention patients showed a slight but significant decrease of HBA1C levels in the second semester of 1994 (from 7.0 to 6.8, P = 0.03), control patients also showed a slightly decreased group mean, but this change was not significant (from 6.6 to 6.5, P = 0.52). The magnitudes of these mean differences, however, were not significantly different (intervention group: 0.21; control group: 0.12, P = 0.68).\n The electronic communication network for exchanging consultation outcomes significantly increased frequency of communication and the availability of data to the general practitioner on diagnostic procedures performed in the hospital, thus providing more complete information about the care that patients are receiving. A large-scale experiment over a longer period of time is needed to assess the effects of improved communication on quality of care.", "A crossover randomized controlled trial of cycles of quality assurance in 16 primary care (8 medical, 8 pediatric) group practices was conducted. Of four medical and four pediatric tasks important to patient outcome, two were randomly assigned to experimental intervention (a quality assurance cycle), and two were also measured and used as blinded controls for each medical or pediatric group practice. Task performance was measured in each group for 12 months prior to, 9 months during, and 9 months after the experimental intervention, using as a performance score the percentage of evaluation criteria failed of those applicable to a case. As a result of quality assurance intervention, quality of performance was significantly improved in two of the tasks (P less than 0.0001, with 6.7, and 9.8 percentage points improvement), and marginally improved in one task (P = 0.06, 5.7 percentage points improvement). Surprisingly, tasks with lower perceived effect on patient health (low physician motivation) had greater improvement in quality. Unimproved tasks were associated with the perceived need for delivery system changes beyond the immediate control of the individual practitioner.", "To evaluate the impact of a continuous quality improvement (CQI) intervention on glycemic control of patients with diabetes mellitus attending a primary care clinic.\n A CQI process designed by the Minnesota Department of Health to improve diabetes care was implemented at a volunteer clinic, with another similar clinic not using the CQI process assessed for comparison. Adults with diabetes were identified at both clinics using diagnostic and pharmacy databases. Glycosylated hemoglobin (HbA1c) values (reference range, 4.3%-6.1%) and out-patient utilization and charges were compared for all patients with diabetes at each clinic for the 12 months before and 18 months after initiation of the CQI intervention.\n The mean HbA1c value at the intervention clinic fell from 8.9% at baseline to 8.4% at 12 months and to 7.9% at 18 months. The mean HbA1c value at the comparison clinic was 8.9% at baseline, 8.9% at 12 months, and 8.8% at 18 months (difference between clinics, t = 4.13, P < .001). Differences after the intervention in the proportion of patients at the comparison clinic (n = 121) vs the intervention clinic (n = 122) with HbA1c values of 8% or less (40% vs 51%), between 8% and 10% (33% vs 37%), and 10% or greater (27% vs 12%) were unlikely due to chance (chi 2 = 9.7, 2 df, P = .008). The intervention was not associated with increased utilization of outpatient visits or outpatient charges.\n Involvement of nurses, physicians, and managers in a CQI process can improve patients' glycemic control in some health maintenance organization primary care settings, without increasing utilization or charges. Health maintenance organizations should consider CQI as one possible method to improve diabetes outcomes.", "This paper introduces a new and innovative approach to diabetes management in the primary-care setting. Staged diabetes management (SDM) represents a four-year effort to develop and test a data-based approach to diabetes management that could be easily adapted to a variety of health-care settings in which diabetes management is principally under the direction of primary-care physicians was limited access to specialists. After testing under controlled circumstances at the International Diabetes Center (Minneapolis, MN), SDM was subjected to substantial field trials under conditions that represent the scope and variety of primary-care practices in diabetes. The following represents the work of several investigators who independently undertook a review of SDM.", "To determine whether multiple mailed patient reminders can produce an increase in the rate of diabetic retinal examinations (DRE) over that seen with a single reminder.\n All diabetic members > or = 18 years who were enrolled in a large network-based health maintenance organization (HMO) in California from August 1996 to July 1997 were identified using claims and pharmacy databases. Members who had no record of DRE in the HMO's claims database were then randomized into two groups. Both groups received mailed educational materials and a reminder to obtain the examination. Their physician groups also received a letter explaining the program, current guidelines for DRE, and a list of their diabetes patients with their DRE status. The single intervention group received no additional reminders. The multiple intervention group received additional reminders at 3, 6, and 9 months after baseline if they continued with no record of service, as determined from the claims database.\n The study cohort comprised 19,523 diabetic members, which were randomized into single (n = 9,614) and multiple (n = 9,909) intervention groups. There was an increase in monthly DRE rates after the intervention in August 1996 for both intervention groups. After the second reminder was sent to the multiple intervention group, the percentage of diabetic members receiving DRE was higher than the single intervention group. Rates before and after the third intervention were not significantly different, nor were monthly differences found. There was a significant difference in overall annual DRE rates between the groups (P = 0.023).\n Multiple patient reminders are more effective than single reminders in improving DRE rates in a managed care setting. However, the improvement noted was clinically small and appeared only after the second reminder; no incremental improvement was seen with additional reminders. Resources used for multiple reminders aimed at diabetic retinopathy might better be spent on other approaches to reducing complications of diabetes.", "To evaluate integrated care for diabetes in clinical, psychosocial, and economic terms.\n Pragmatic randomised trial.\n Hospital diabetic clinic and three general practice groups in Grampian.\n 274 adult diabetic patients attending a hospital clinic and registered with one of three general practices.\n Random allocation to conventional hospital clinic care or integrated care. Integrated care patients seen in general practice every three or four months and in the hospital clinic annually. General practitioners were given written guidelines for integrated care.\n Metabolic control, psychosocial status, knowledge of diabetes, beliefs about control of diabetes, satisfaction with treatment, disruption of normal activities, numbers of consultations and admissions, frequency of metabolic monitoring, costs to patients and NHS.\n A higher proportion of patients defaulted from conventional care (14 (10%)) than from integrated care (4 (3%), 95% confidence interval of difference 2% to 13%). After two years no significant differences were found between the groups in metabolic control, psychosocial status, knowledge, beliefs about control, satisfaction with treatment, unscheduled admissions, or disruption of normal activities. Integrated care was as effective for insulin dependent as non-insulin dependent patients. Patients in integrated care had more visits and higher frequencies of examination. Costs to patients were lower in integrated care (mean 1.70 pounds) than in conventional care (8 pounds). 88% of patients who experienced integrated care wished to continue with it.\n This model of integrated care for diabetes was at least as effective as conventional hospital clinic care.", "To assess the effect of additional training of practice nurses and general practitioners in patient centred care on the lifestyle and psychological and physiological status of patients with newly diagnosed type 2 diabetes.\n Pragmatic parallel group design, with randomisation between practice teams to routine care (comparison group) or routine care plus additional training (intervention group); analysis at one year, allowing for practice effects and stratifiers; self reporting by patients on communication with practitioners, satisfaction with treatment, style of care, and lifestyle.\n 41 practices (21 in intervention group, 20 in comparison group) in a health region in southern England.\n 250/360 patients (aged 30-70 years) diagnosed with type 2 diabetes and completing follow up at one year (142 in intervention group, 108 in comparison group).\n 1.5 days' group training for the doctors and nurses-introducing evidence for and skills of patient centred care and a patient held booklet encouraging questions.\n Quality of life, wellbeing, haemoglobin A1c and lipid concentrations, blood pressure, body mass index (kg/m2).\n Compared with patients in the C group, those in the intervention group reported better communication with the doctors (odds ratio 2.8; 95% confidence interval 1.8 to 4.3) and greater treatment satisfaction (1.6; 1.1 to 2.5) and wellbeing (difference in means (d) 2.8; 0.4 to 5.2). However, their body mass index was significantly higher (d=2.0; 0.3 to 3.8), as were triglyceride concentrations (d=0.4 mmol/l; 0.07 to 0.73 mmol/l), whereas knowledge scores were lower (d=-2.74; -0.23 to -5.25). Differences in lifestyle and glycaemic control were not significant.\n The findings suggest greater attention to the consultation process than to preventive care among trained practitioners; those committed to achieving the benefits of patient centred consulting should not lose the focus on disease management.", "In primary care it is difficult to treat the growing number of non-insulin-dependent diabetic (NIDDM) patients according to (inter)national guidelines. A prospective, controlled cohort study was designed to assess the intermediate term (2 years) effect of structured NIDDM care in general practice with and without 'diabetes service' support on glycaemic control, cardiovascular risk factors, general well-being and treatment satisfaction. The 'diabetes service', supervised by a diabetologist, included a patient registration system, consultation facilities of a dietitian and diabetes nurse educator, and protocolized blood glucose lowering therapy advice which included home blood glucose monitoring and insulin therapy. In the study group (SG; 22 general practices), 350 known NIDDM patients over 40 years of age (206 women; mean age 65.3 +/- SD 11.9; diabetes duration 5.9 +/- 5.4 years) were followed for 2 years. The control group (CG; 6 general practices) consisted of 68 patients (28 women; age 64.6 +/- 10.3; diabetes duration 6.3 +/- 6.4 years). Mean HbA1c (reference 4.3-6.1%) fell from 7.4 to 7.0% in SG and rose from 7.4 to 7.6% in CG during follow-up (p = 0.004). The percentage of patients with poor control (HbA1c > 8.5%) shifted from 21.4 to 11.7% in SG, but from 23.5 to 27.9% in CG (p = 0.008). Good control (HbA1c < 7.0%) was achieved in 54.3% (SG; at entry 43.4%) and 44.1% (CG; at entry 54.4%) (p = 0.013). Insulin therapy was started in 29.7% (SG) and 8.8% (CG) of the patients (p = 0.000) with low risk of severe hypoglycaemia (0.019/patient year). Mean levels of total and HDL-cholesterol (SG), triglycerides (SG) and diastolic blood pressure (SG + CG) and the percentage of smokers (SG) declined significantly, but the prevalence of these risk factors remained high. General well-being (SG) did not change during intensified therapy. Treatment satisfaction (SG) tended to improve. Implementation of structured care, including education and therapeutic advice, results in sustained good glycaemic control in the majority of NIDDM patients in primary care, with low risk of hypoglycaemia. Lowering cardiovascular risk requires more than reporting results and referral to guidelines.", "While lower-extremity amputation (LEA) is a frequent complication of diabetes, effective strategies for the prevention of LEA in primary care settings have not been extensively studied.\n This prospective study of American Indians with diabetes in a rural primary care clinic was divided into three periods: the standard care period (1986 to 1989), during which patients received foot care at the discretion of the primary care provider; the public health period (1990 to 1993), during which patients were screened for foot problems and high-risk individuals received foot care education and protective footwear; and the Staged Diabetes Management (SDM) period (1994 to 1996), during which comprehensive guidelines for diabetic foot management were adapted by the primary care clinicians to their practices and were systematically implemented.\n A total of 639 individuals contributed 4322 diabetic person-years during the three periods of observation. Patient sex distribution, mean age, and mean duration of diabetes were similar i the three periods. The average annual LEA incidence was 29/1000 diabetic person-years for the standard care period (n = 42), 21/1000 for the public health period (n = 33), and 15/1000 for the SDM period (n = 20), an overall 48% reduction (P = .016). Overall, the incidence of a first amputation declined from 21/1000 to 6/1000 (P < .0001).\n The customization and systematic implementation of practice guidelines by local primary care providers was associated with improved diabetic foot care outcomes. SDM has relevance to primary care organizations seeking to improve outcomes for patients with diabetes.", "Our objective was to evaluate the effect of training in a patient-centred intervention for GPs and practice nurses on outcomes for patients with Type II diabetes.\n We carried out a randomized controlled trial within general practices as the basis for randomization and a before-and-after design for measures of patient outcome. A parallel process study examined the use of the method by professionals. The study was carried out in 29 general practices in South Glamorgan who had participated for at least 2 years in a local scheme of audit and CME in relation to Type II diabetes care. The subjects were 252 Type II diabetic patients recruited by 15 experimental and 14 control practices. The main outcome measures were changes in glycosylated haemoglobin, patient satisfaction with care and treatment, functional health status and professional ability to apply the intervention.\n Professionals adopted the innovative method with enthusiasm, but after 2 years only 19% continued to apply the method systematically. The trial was, therefore, unable to demonstrate significant biochemical or functional improvements. This highlights the need to understand the factors associated with professional uptake and subsequent ability to sustain changes in behaviour.\n The efficacy of this behavioural intervention remains unproved, despite its acceptability to professional staff. Detailed and prolonged development and testing of behavioural interventions is an essential first step before embarking on randomized controlled trials which involve complex behavioural changes in professionals or patients.", "Treatment of patients with diabetes often falls short of recommended process and outcome guidelines. To improve the quality of the provided diabetes care, a program (the Comprehensive Diabetes Care Service [CDCS]) using a computerizing tracking and recall system in conjunction with nurses following protocols was implemented in a managed care setting. The impact of this program was studied and compared to the care provided to patients in another managed care setting.\n Patients followed in the CDCS who completed a diabetes education course were compared with patients followed in a group model health maintenance organization (GMH) who also completed a diabetes education course. CDCS patients received routine care in the program. GMH patients came to the CDCS yearly to have a diabetes evaluation. A chart review was also performed on their GMH outpatient records.\n Initial HbA1c levels were higher in the CDCS group than in the GMH group (median of 11.9 vs. 10.0%). In the CDCS patients, HbA1c levels not only fell significantly but were also significantly lower (P < 0.05) than in the GMH patients during the 2nd and 3rd year of follow-up care. There were no significant changes in HbA1c levels in the GMH patients. When CDCS patients were divided into compliant and noncompliant patients, the median HbA1c levels in compliant patients was 8.2%, compared with 11.5% in the noncompliant group. The CDCS patients who needed treatment for hypercholesterolemia were more likely to have a lowering of their cholesterol levels than the GMH patients. All process measures, such as yearly measurement of HbA1c levels, lipid levels, and foot and retinal exams, occurred much more frequently in the CDCS patients.\n The system developed and implemented for managing diabetes improved both outcome and process measures. The comparison group, followed at another managed care setting, received the care consistent with the average (suboptimal) quality of care provided to patients with diabetes in the U.S. Therefore, by using innovative systems of management, the treatment of patients with diabetes can be greatly improved.", "We conducted a pilot randomised trial of computerised templates for the management of asthma and diabetes in general practice in six general practices in North London. Uptake of the guidelines by general practitioners and practice nurses was assessed using qualitative (semi-structured interviews designed to assess the users' views) and quantitative (change in use of the template during the study period) outcome measures. The practice nurses used the templates frequently but general practitioners rarely used them. Several reasons were offered for non-use of the templates, such as the length of the template and non-involvement in the care of asthma or diabetes. Despite this, however, health professionals were favourably disposed to the use of templates for general clinical care. Pilot investigations of computerised templates are best achieved by observational or quasi-experimental methods rather than a randomised controlled trial. The use of both qualitative and quantitative methods in this study allowed exploration of the barriers to use of computers.", "The effects of a new integrated system of diabetes care with an enhanced role of the diabetes specialist nurse based in a purposed design diabetes centre, on diabetes control, attendance and cancellation rates, and admission for diabetic emergencies have been reviewed. Glycaemic control was examined in: (a) a cohort of 163 insulin-treated and 47 non-insulin treated diabetic subjects (age < 65 years) studied prospectively before and 3 years following the introduction of a new system of care; (b) a second cohort of more elderly patients aged greater than 65 years studied for the 3 years after the change over; (c) a cross-sectional study of the clinic population (n = 700) the year before and 3 years after the changeover; (d) a group of patients attending standard unaltered clinics in the same district (n = 157). Significant and sustained falls in HbA1 were observed in all groups of subjects attending the centre, with the means for those aged less than 65 falling from 11.9 +/- 2.3% to 9.9 +/- 1.9% and for those aged over 65 from a mean of 11.7 +/- 2.0% to 10.3 +/- 2.3%, 3 years later. The cross-sectional study provided similar results with a mean HbA1 of 12.2 +/- 3.0% prior to changeover and 10.4 +/- 4.4%, 3 years later. Smaller but significant changes were observed in patients continuing to attend the routine clinic (from 12.2 +/- 2.3% to 11.3 +/- 2.6%) over a similar period. Yearly admission rates for ketoacidosis and hypoglycaemia fell from 44 and 23, to 33 and 5 per annum, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "To examine whether a telephone-delivered intervention (TDI), designed to improve glycemic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), improved coronary risk factors in high-risk patients.\n This randomized controlled trial involved 275 veterans with NIDDM followed in a general medical clinic. Intervention (TDI) patients were telephoned at least monthly by a nurse. Calls emphasized compliance with the medical regimen (diet, medications, and exercise), encouraged behavioral changes, and facilitated referrals to a dietitian or smoking cessation clinic. Control patients received no such calls. Baseline and 12-month follow-up measurements included fasting lipid profiles, weight, smoking status (self-reported; cessation verified by measurement of exhaled CO), adherence to diet and exercise (self-reported), appointments, and medications (hospital computerized data base).\n After 12 months, equal numbers of obese patients in the two groups reported adhering to a diabetic diet and exercising, although more obese TDI patients had seen a dietitian (30 vs. 7%, P = 0.003). Weight loss was not seen in either group (-0.9 +/- 5.3 vs. -0.1 +/- 3.6 kg, P = 0.202). Hyperlipidemic TDI patients were more likely to see a dietitian (31 vs. 6%, P = 0.003) and receive lipid-lowering medications (22 vs. 9%, P = 0.096), but serum cholesterol reduction was similar between groups (-11.7 +/- 33.4 vs. -4.3 +/- 32.7 mg/dl, P = 0.270); comparable results were seen for high-density lipoprotein, low-density lipoprotein, and triglyceride levels. More TDI group smokers reported quitting (26 vs. 0%, P = 0.033), but the difference was not significant for CO-verified abstention (10 vs. 0%, P = 0.231).\n The TDI improved self-reported adherence to regimens that might reduce coronary risk, but had little effect on objective measures of risk.", "Effects of a diabetes control program were evaluated in 17 primary health centers after 18 months' participation (17 nonparticipating centers served as controls). Studied were the effects of the program on the organization of diabetes care, on the process of care in terms of services delivered to patients, and on the outcomes of care as measured by improved self-care, dietary knowledge, and HbA1c values. While findings showed that patients from the intervention centers received a higher quality of service and monitored their blood glucose levels more often than did patients from the control centers, they did not demonstrate significantly better metabolic control. The reasons for this, and ways to improve the program are discussed.", "Clinical guidelines are designed to assist in the management of specific diseases; however, these guidelines are often neglected in the delivery of care. The purpose of this study was to determine whether clinician use of an clinical practice guideline would increase in response to having, at the patient visit, a decision support system based on a practice guideline that generates a customized management protocol for the individual patient using data from the patient's electronic medical record.\n In a 6-month controlled trial at a primary care clinic, 58 primary care clinicians were randomized to receive either a special encounter form with the computer-generated guideline recommendations or a standard encounter form. The effect of computer-generated advice on clinician behavior was measured as rate of compliance with guideline recommendations. Data from 30 clinicians were analyzed; data from 28 clinicians were excluded because these clinicians did not meet predefined criteria for minimum exposure to diabetic patient care.\n Availability of patient management recommendations generated by the decision support system resulted in a two-fold increase in clinician compliance with care guidelines for diabetes mellitus (P = 0.01). Median compliance for the group receiving the recommendations was 32.0% versus 15.6% for the control group.\n Decision support based on a clinical practice guideline is an effective tool for assisting clinicians in the management of diabetic patients. This decision support system provides a model for how a clinical practice guideline can be integrated into the care process by computer to assist clinicians in managing a specific disease through helping them comply with care standards. Use of decision support systems based on clinical practice guidelines could ultimately improve the quality of medical care.", "This project tested the importance of enhanced information transfer of home monitoring results to health care providers. The study tested whether computer-assisted communication of medical information between the chronic care patient and the physician can result in health care benefit. The information tools were constructed/adapted as a test of this hypothesis for diabetes mellitus. Patients connected a glucometer to an intelligent modem weekly for six to nine months. Graphical and mathematical tools extracted and emphasized the information content of the home monitoring data arriving at the central site. Data smoothing, trend analysis, and calculation of quality control statistics were incorporated into a graphical time series oriented report that was used by the health care provider during an outpatient visit. The integrated home monitoring system was tested on 20 patients with diabetes in a double cross-over design over a 15-month period. A significant improvement in serum glucose control as measured by glycated hemoglobin was shown in the study group, but not in the control group.", "Efforts to improve care have focused on population-based approaches, though little practical information exists about implementation.\n This report reviews relevant literature on teamwork in the context of a time-series evaluation of a demonstration project to reorganize care of a single panel of patients in a managed care setting. The proportion of the study panel achieving recommended levels for breast and colon cancer screening, warfarin control, and diabetic eye care was compared with the surrounding practice panels and the managed care population as a whole. Using unconditional logistic regression, we compared changes within populations between March 1993 and March 1995, and the rate of change between populations during the same period.\n A model of team care was successfully implemented. Colon (occult blood in the stool) and breast (mammography) screening increased more rapidly in the study population than in the surrounding practices or plan as a whole (P < 0.05 for all comparisons). There was no significant improvement in warfarin control or diabetic eye examinations, though absolute increases occurred.\n This work shows that a team approach to population-based care is a real option. Such an approach, however, will not generalize to other settings or all conditions, and its implementation involves some major challenges.", "To determine whether locally developed guidelines on asthma and diabetes disseminated through practice based education improve quality of care in non-training, inner city general practices.\n Randomised controlled trial with each practice receiving one set of guidelines but providing data on the management of both conditions.\n 24 inner city, non-training general practices.\n East London.\n Recording of key variables in patient records (asthma: peak flow rate, review of inhaler technique, review of asthma symptoms, prophylaxis, occupation, and smoking habit; diabetes: blood glucose concentration, glycaemic control, funduscopy, feet examination, weight, and smoking habit); size of practice disease registers; prescribing in asthma; and use of structured consultation \"prompts.\"\n In practices receiving diabetes guidelines, significant improvements in recording were seen for all seven diabetes variables. Both groups of practices showed improved recording of review of inhaler technique, smoking habit, and review of asthma symptoms. In practices receiving asthma guidelines, further improvement was seen only in recording of review of inhaler technique and quality of prescribing in asthma. Sizes of disease registers were unchanged. The use of structured prompts was associated with improved recording of four of seven variables on diabetes and all six variables on asthma.\n Local guidelines disseminated via practice based education improve the management of diabetes and possibly of asthma in inner city, non-training practices. The use of simple prompts may enhance this improvement.", "Control of hyperglycemia delays or prevents complications of diabetes, but many persons with diabetes do not achieve optimal control.\n To compare diabetes control in patients receiving nurse case management and patients receiving usual care.\n Randomized, controlled trial.\n Primary care clinics in a group-model health maintenance organization (HMO).\n 17 patients with type 1 diabetes mellitus and 121 patients with type 2 diabetes mellitus.\n The nurse case manager followed written management algorithms under the direction of a family physician and an endocrinologist. Changes in therapy were communicated to primary care physicians. All patients received ongoing care through their primary care physicians.\n The primary outcome, hemoglobin A1c (HbA1c) value, was measured at baseline and at 12 months. Fasting blood glucose levels, medication type and dose, body weight, blood pressure, lipid levels, patient-perceived health status, episodes of severe hypoglycemia, and emergency department and hospital admissions were also assessed.\n 72% of patients completed follow-up. Patients in the nurse case management group had mean decreases of 1.7 percentage points in HbA1c values and 43 mg/dL (2.38 mmol/L) in fasting glucose levels; patients in the usual care group had decreases of 0.6 percentage points in HbA1c values and 15 mg/dL (0.83 mmol/L) in fasting glucose levels (P < 0.01). Self-reported health status improved in the nurse case management group (P = 0.02). The nurse case management intervention was not associated with statistically significant changes in medication type or dose, body weight, blood pressure, or lipids or with adverse events.\n A nurse case manager with considerable management responsibility can, in association with primary care physicians and an endocrinologist, help improve glycemic control in diabetic patients in a group-model HMO.", "The purpose of this study was to evaluate the efficacy of using a telecommunication system to assist in the outpatient management of pediatric patients with insulin-dependent diabetes. Metabolic control, patients' psychosocial status, family functioning, perceived quality of life, patterns of parental/child responsibility for daily diabetes maintenance, and nursing time-on-task were evaluated. One hundred six pediatric patients (mean age = 13.3 years) were randomly assigned to an experimental or control outpatient clinic for 1 year. Experimental subjects transmitted self-monitoring blood glucose data by modem to the hospital every 2 weeks. Transmitted data were reviewed by nurse practitioners who telephoned subjects to discuss regimen adjustments. Control subjects received standard care with regimen adjustments made by physicians. There were no significant between-group differences for metabolic control, rates of hospitalization or emergency-room visits, psychological status, general family functioning, quality of life, or parent-child responsibility. A significant decrease was noted in nursing time-on-task for experimental subjects.", "The Diabetes Education Study was a controlled trial of the effects of physician and patient education. This article describes an educational program for internal medicine residents and its effects on ambulatory diabetes management practices. Forty-five of 86 residents practicing in the general medicine clinic of a university-affiliated city/county hospital were assigned randomly to receive a multifaceted program intended to 1) provide specific care recommendations, 2) teach necessary skills, and 3) make the professional and institutional environment more supportive. During the subsequent 11 months, 323 diabetic patients were interviewed and their records audited for evidence of changes in care. Experimental residents utilized fasting blood glucose determinations more often than controls (i.e., during 40% of visits vs. 31%, p = 0.004). Experimental residents also engaged more frequently in a variety of recommended dietary management recommendations. Isolated differences in monitoring/management of chronic complications also were found (e.g., lipid screening: 70% of experimental residents' patients vs. 58%, p = 0.016). Intensive, multifaceted programs of this nature are concluded to result in improvements in diabetes care, over and above that which is attainable through routine methods of clinical training for residents.", "To evaluate the effect of a patient, health care provider, and systems intervention on the prevalence of risk factors for lower extremity amputation in patients with non-insulin-dependent diabetes.\n Blinded, randomized, controlled trial.\n Academic general medicine practice.\n Of the 395 patients with non-insulin-dependent diabetes who underwent the initial patient assessment, 352 completed the study.\n The 12-month intervention was multifaceted. Patients received foot-care education and entered into a behavioral contract for desired self-foot care, which was reinforced through telephone and postcard reminders. Health care providers were given practice guidelines and informational flow sheets on foot-related risk factors for amputation in diabetic patients. In addition, the folders for intervention patients had special identifiers that prompted health care providers to: 1) ask that patients remove their footwear, 2) perform foot examinations, and 3) provide foot-care education.\n Patients receiving the intervention were less likely than control patients to have serious foot lesions (baseline prevalence, 2.9%; odds ratio, 0.41 [95% CI, 0.16 to 1.00]; P = 0.05) and other dermatologic abnormalities. Also, they were more likely to report appropriate self-foot-care behaviors, to have foot examinations during office visits (68% compared with 28%; P < 0.001), and to receive foot-care education from health care providers (42% compared with 18%; P < 0.001). Physicians assigned to intervention patients were more likely than physicians assigned to control patients to examine patients' feet for ulcers, pulses, and abnormal dermatologic conditions and to refer patients to the podiatry clinic (10.6% compared with 5.0%; P = 0.04).\n An intervention designed to reduce risk factors for lower extremity amputations positively affected patient self-foot-care behavior as well as the foot care given by health care providers and reduced the prevalence of lower extremity clinical disease in patients with diabetes." ]

[ "20478877", "18391133", "9592630", "10087688", "9808930", "18281410", "18978634", "15502599" ]

[ "Treatment of Resistant Depression in Adolescents (TORDIA): week 24 outcomes.", "Achievement and maintenance of sustained response during the Treatment for Adolescents With Depression Study continuation and maintenance therapy.", "Fluoxetine in child and adolescent depression: acute and maintenance treatment.", "Cognitive-behavioral treatment of adolescent depression: efficacy of acute group treatment and booster sessions.", "Rapid response to psychosocial treatment for adolescent depression: a two-year follow-up.", "Fluoxetine versus placebo in preventing relapse of major depression in children and adolescents.", "Cognitive-behavioral therapy to prevent relapse in pediatric responders to pharmacotherapy for major depressive disorder.", "Fluoxetine treatment for prevention of relapse of depression in children and adolescents: a double-blind, placebo-controlled study." ]

[ "The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial after 24 weeks of treatment, including remission and relapse rates and predictors of treatment outcome.\n Adolescents (ages 12-18 years) with selective serotonin reuptake inhibitor (SSRI)-resistant depression were randomly assigned to either a medication switch alone (alternate SSRI or venlafaxine) or a medication switch plus cognitive-behavioral therapy (CBT). At week 12, responders could continue in their assigned treatment arm and nonresponders received open treatment (medication and/or CBT) for 12 more weeks (24 weeks total). The primary outcomes were remission and relapse, defined by the Adolescent Longitudinal Interval Follow-Up Evaluation as rated by an independent evaluator.\n Of 334 adolescents enrolled in the study, 38.9% achieved remission by 24 weeks, and initial treatment assignment did not affect rates of remission. Likelihood of remission was much higher (61.6% versus 18.3%) and time to remission was much faster among those who had already demonstrated clinical response by week 12. Remission was also higher among those with lower baseline depression, hopelessness, and self-reported anxiety. At week 12, lower depression, hopelessness, anxiety, suicidal ideation, family conflict, and absence of comorbid dysthymia, anxiety, and drug/alcohol use and impairment also predicted remission. Of those who responded by week 12, 19.6% had a relapse of depression by week 24.\n Continued treatment for depression among treatment-resistant adolescents results in remission in approximately one-third of patients, similar to adults. Eventual remission is evident within the first 6 weeks in many, suggesting that earlier intervention among nonresponders could be important.", "The Treatment for Adolescents With Depression Study evaluated fluoxetine (FLX), cognitive behavioral therapy (CBT), and FLX/CBT combination (COMB) vs pill placebo in 439 adolescents with major depressive disorder. Treatment consisted of 3 stages: (1) acute (12 weeks), (2) continuation (6 weeks), and (3) maintenance (18 weeks).\n To examine rates of achieving and maintaining sustained response during continuation and maintenance treatments.\n Randomized controlled trial. Response was determined by blinded independent evaluators.\n Thirteen US sites.\n Two hundred forty-two FLX, CBT, and COMB patients in their assigned treatment at the end of stage 1.\n Stage 2 treatment varied based on stage 1 response. Stage 3 consisted of 3 CBT and/or pharmacotherapy sessions and, if applicable, continued medication.\n Sustained response was defined as 2 consecutive Clinical Global Impression-Improvement ratings of 1 or 2 (\"full response\"). Patients achieving sustained response were classified on subsequent nonresponse status.\n Among 95 patients (39.3%) who had not achieved sustained response by week 12 (29.1% COMB, 32.5% FLX, and 57.9% CBT), sustained response rates during stages 2 and 3 were 80.0% COMB, 61.5% FLX, and 77.3% CBT (difference not significant). Among the remaining 147 patients (60.7%) who achieved sustained response by week 12, CBT patients were more likely than FLX patients to maintain sustained response through week 36 (96.9% vs 74.1%; P = .007; 88.5% of COMB patients maintained sustained response through week 36). Total rates of sustained response by week 36 were 88.4% COMB, 82.5% FLX, and 75.0% CBT.\n Most adolescents with depression who had not achieved sustained response during acute treatment did achieve that level of improvement during continuation and maintenance therapies. The possibility that CBT may help the subset of adolescents with depression who achieve early sustained response maintain their response warrants further investigation.\n clinicaltrials.gov Identifier: NCT00006286.", "The objective was to present naturalistic 1-year follow-up information of 96 child and adolescent outpatients with major depressive disorder who had been randomized in an 8-week double-blind, placebo-controlled trial of fluoxetine. Subjects were children and adolescents, ages 8-18 years, who were entered in a randomized clinical trial of fluoxetine. Following the acute treatment trial, treatment was not controlled. At 6 months and 1 year, the subjects and parents were interviewed using the Kiddie Longitudinal Interval Follow-up Evaluation (K-LIFE) for course of depression. Eighty-seven of the 96 subjects were followed for 1 year. Of these, 74 (85%) recovered from the depressive episode during that time (47 on fluoxetine, 22 on no medication, and 5 on other antidepressants or lithium). Twenty-nine of the subjects (39%) who recovered had a recurrence of depression during the 1-year follow-up, with 55% of these occurring within 6 months. Results of this study are similar to adult studies, with respect to response and recovery of depressive episodes. Most patients (85%) recover from the episode within 1 year, but approximately 40% have a recurrence within 12 months, which is a higher recurrence rate than in adults. Recovery was associated with younger age, lower severity of depressive symptoms, higher family functioning, and fewer comorbid diagnoses. Recurrence, which occurs both on and off medication, was difficult to predict, as there was little clinical data associated with recurrence in this population.", "This trial examined the effects of both acute and maintenance cognitive-behavioral therapy (CBT) for depressed adolescents.\n Adolescents with major depression or dysthymia (N = 123) were randomly assigned to 1 of 3 eight-week acute conditions: adolescent group CBT (16 two-hour sessions); adolescent group CBT with a separate parent group; or waitlist control. Subsequently, participants completing the acute CBT groups were randomly reassigned to 1 of 3 conditions for the 24-month follow-up period: assessments every 4 months with booster sessions; assessments only every 4 months; or assessments only every 12 months.\n Acute CBT groups yielded higher depression recovery rates (66.7%) than the waitlist (48.1%), and greater reduction in self-reported depression. Outcomes for the adolescent-only and adolescent + parent conditions were not significantly different. Rates of recurrence during the 2-year follow-up were lower than found with treated adult depression. The booster sessions did not reduce the rate of recurrence in the follow-up period but appeared to accelerate recovery among participants who were still depressed at the end of the acute phase.\n The findings, which replicate and expand upon a previous study, support the growing evidence that CBT is an effective intervention for adolescent depression.", "To examine the differential course and treatment outcome of patients who participated in a randomized clinical trial, comparing cognitive, family, and supportive psychotherapies for adolescent major depressive disorder.\n In a sample of 100 depressed adolescents, remission, clinical recovery, recurrence, and functional improvement were examined at the end of acute treatment and at 1- and 2-year follow-up, according to their type of response to treatment. Rapid response was defined as a decline of > or = 50% in the Beck Depression Inventory (BDI) score from pretreatment until the beginning of the second session of psychotherapy, intermediate as a decline of < 50% but > 0%, and initial nonresponse as a BDI score that stayed the same or increased.\n Rapid responders showed a better outcome at acute treatment, 1-year, and in some measures, 2-year follow-up. For those who had recurrences over time, rapid responders showed a longer period before recurrence. Subjects were most likely to respond rapidly, or not at all, in the supportive cell.\n These findings suggest that milder forms of depression may benefit from initial supportive therapy or short trials of more specialized types of psychotherapy. The use of a placebo run-in period might help to \"wash out\" nonspecific responders.", "The authors compared fluoxetine and placebo in continuation treatment to prevent relapse of major depressive disorder in children and adolescents.\n After a detailed evaluation, children and adolescents 7-18 years of age with major depressive disorder were treated openly with fluoxetine. Those who had an adequate response after 12 weeks, as indicated by a Clinical Global Impression improvement score of 1 or 2 and a decrease of at least 50% in Children's Depression Rating Scale-Revised score, were randomly assigned to receive fluoxetine or placebo for an additional 6 months. The primary outcome measures were relapse and time to relapse. Relapse was defined as either a score of 40 or higher on the Children's Depression Rating Scale with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. Additional analyses were conducted with relapse defined only as a score of 40 or higher on the Children's Depression Rating Scale.\n Of 168 participants enrolled in acute fluoxetine treatment, 102 were randomly assigned to continuation treatment with fluoxetine (N=50) or placebo (N=52). Of these, 21 participants (42.0%) in the fluoxetine group relapsed, compared with 36 (69.2%) in the placebo group, a significant difference. Similarly, under the stricter definition of relapse, fewer participants in the fluoxetine group relapsed (N=11; 22.0%) than in the placebo group (N=25; 48.1%). Time to relapse was significantly shorter in the placebo group.\n Continuation treatment with fluoxetine was superior to placebo in preventing relapse and in increasing time to relapse in children and adolescents with major depression.", "We present results of a feasibility test of a sequential treatment strategy using continuation phase cognitive-behavioral therapy (CBT) to prevent relapse in youths with major depressive disorder (MDD) who have responded to acute phase pharmacotherapy.\n Forty-six youths (ages 11-18 years) who had responded to 12 weeks of treatment with fluoxetine were randomized to receive either 6 months of continued antidepressant medication management (MM) or antidepressant MM plus relapse prevention CBT (MM+CBT). Primary outcome was time to relapse, defined as a Childhood Depression Rating Scale-Revised score of 40 or higher and 2 weeks of symptom worsening or clinical deterioration warranting alteration of treatment to prevent full relapse.\n Cox proportional hazards regression, adjusting for depression severity at randomization and for the hazard of relapsing by age across the trial, revealed that participants in the MM treatment group had a significantly greater risk for relapse than those in the MM+CBT treatment group (hazard ratio = 8.80; 95% confidence interval 1.01-76.89; chi = 3.86, p =.049) during 6 months of continuation treatment. In addition, patient satisfaction was significantly higher in the MM+CBT group. No differences were found between the two treatment groups on attrition rate, serious adverse events, and overall global functioning.\n These preliminary results suggest that continuation phase CBT reduces the risk for relapse by eightfold compared with pharmacotherapy responders who received antidepressant medication alone during the 6-month continuation phase.", "To compare fluoxetine 20 to 60 mg/day with placebo for prevention of relapse of major depressive disorder in children and adolescents who had achieved Children's Depression Rating Scale, Revised scores of < or =28 during treatment with fluoxetine 20 to 60 mg.\n In this 32-week relapse-prevention phase of a double-blind, multicenter, placebo-controlled 51-week study, 20 patients continued to receive their fixed dose of fluoxetine (F/F group), while 20 similar patients were switched to placebo (F/P group). Definition of relapse for the primary analysis was a Children's Depression Rating Scale, Revised score of >40 with a 2-week history of clinical deterioration or relapse in the opinion of the physician. Adverse events were compared between treatment groups to assess discontinuation-emergent adverse events.\n Mean time to relapse was longer in the F/F recipients than in the F/P recipients (p=.046). Relapse occurred in an estimated 34% in the F/F cohort and 60% in the F/P cohort. Incidence of adverse events and tolerability were similar in the F/F and F/P groups, suggesting that fluoxetine is not associated with significant discontinuation events.\n Fluoxetine 20 to 60 mg/day was well tolerated and can significantly delay relapse of major depressive disorder symptoms in children and adolescents." ]

[ "8530644", "15236979", "19031222", "1899393", "8174724", "1752926", "17433313", "10360912", "16595218" ]

[ "Induction of pre-ovulatory gonadotrophin surge with gonadotrophin-releasing hormone agonist compared to pre-ovulatory injection of human chorionic gonadotrophins for ovulation induction in intrauterine insemination treatment cycles.", "Timing intrauterine insemination either 33 or 39 hours after administration of human chorionic gonadotropin yields the same pregnancy rates as after superovulation therapy.", "Intrauterine insemination with recombinant or urinary human chorionic gonadotropin: A prospective randomized trial.", "Pregnancy rates after timed intercourse or intrauterine insemination after human menopausal gonadotropin stimulation of normal ovulatory cycles: a controlled study.", "Comparison of leuprolide acetate and human chorionic gonadotropin for the induction of ovulation in clomiphene citrate-stimulated cycles.", "A controlled study of human chorionic gonadotrophin induced ovulation versus urinary luteinizing hormone surge for timing of intrauterine insemination.", "Comparison of urinary and recombinant human chorionic gonadotropin during ovulation induction in intrauterine insemination cycles: a prospective randomized clinical trial.", "Prospective, randomized, crossover study to evaluate the benefit of human chorionic gonadotropin-timed versus urinary luteinizing hormone-timed intrauterine inseminations in clomiphene citrate-stimulated treatment cycles.", "Clomiphene citrate monitoring for intrauterine insemination timing: a randomized trial." ]

[ "The clinical outcome of intrauterine insemination (IUI) treatment cycles employing a gonadotrophin-releasing hormone agonist [GnRHa, triptorelin (Decapeptyl)] or human chorionic gonadotrophin (HCG) for ovulation induction was compared. A group of 48 patients presenting with amenorrhoea, oligomenorrhoea or unexplained infertility were all treated with human menopausal gonadotrophins (HMG) from day 5 of the cycle, on an individualized schedule. They were then randomly divided into two groups to receive either a single s.c. injection of 0.1 mg triptorelin or a single i.m. injection of 10,000 IU HCG after follicular maturation. IUI was performed approximately 24 and 48 h following the injection. A transitory increase in serum luteinizing hormone and follicle stimulating hormone concentrations was achieved following injection of GnRHa. A total of 24 patients received 72 treatment cycles with GnRHa, producing 11 conceptions (15.3%) and two abortions (18.2%), resulting in a term pregnancy rate of 13.6%. There were four cases of grade 3-4 ovarian hyperstimulation syndrome (OHSS), two of which were conception cycles. In all, 24 patients underwent 68 cycles treated with HCG, producing 18 conceptions (26.5%) and six abortions (33.3%), resulting in a term pregnancy rate of 19.0%. There were eight cycles of grade 3-4 OHSS, two of which were conception cycles. These results show that an s.c. injection of a relatively low dose of GnRHa can be as effective as HCG in producing pregnancy in IUI treatment cycles.", "To compare a short and long interval between hCG administration and IUI after superovulation for the treatment of infertility.\n Prospective, randomized clinical trial.\n University hospital-based fertility clinic.\n Patients planning superovulation and IUI for the treatment of infertility.\n Patients with >or=2 years of infertility enrolled for superovulation and IUI treatment were randomized to IUI after a short (32-34-hour) or long (38-40-hour) interval after hCG injection. Superovulation was accomplished with hMG or recombinant FSH, with dose adjustment until the maturation of two to five follicles, at which time hCG was given. Sperm was prepared with a gradient centrifugation technique, with IUI performed high up in the uterine fundus.\n Pregnancy rates.\n Of the 348 patient cycles randomized, 270 treatment cycles were initiated. Eighty-one initiated cycles were canceled, leaving 189 completed randomized cycles from 75 patients for analysis. Pregnancy rates were not significantly different between groups. There were pregnancies in 20 of the 96 short hCG-IUI interval cycles (21%) and in 14 of the 93 long hCG-IUI interval cycles (15%) (odds ratio = 0.673, 95% confidence interval 0.297-1.518).\n Pregnancy rates are the same after superovulation therapy whether IUI is done after a short or a long interval after hCG injection.", "Our aim was to compare the efficacy and safety of recombinant and urinary human chorionic gonadotropin (rhCG and uhCG, respectively) for the induction of follicle maturation in women undergoing intrauterine insemination (IUI).\n Patients were randomized to receive rhCG or uhCG. IUI was carried out 24 h (day 1) and 48 h (day 2) after hCG administration, except for all cases in which ovulation occurred after 24 h.\n The two treatments were comparable in terms of progesterone levels on day 7 and day 12. Pregnancy rates were comparable between the treatment groups. Of the 64 women who received rhCG, 29.7% became pregnant; there were 16.7% clinical pregnancies and 3.1% biochemical pregnancies per started cycle, and an ongoing pregnancy rate of 93.7% was reported. Of the 61 patients who received uhCG, 24.6% became pregnant; there were 15.9% clinical pregnancies and 1.1% biochemical pregnancies per started cycle, and ongoing pregnancy rate was 92.9%. No adverse effects were noted in either group.\n The recombinant products can be effectively used instead of urinary products; moreover, apart from the equivalent efficacy in ovulation induction and safety described in this study, it is necessary to consider the advantages provided by the recombinant form.", "Forty-eight patients with male (n = 16) or idiopathic (n = 32) infertility were stimulated with human menopausal gonadotropin. Intrauterine insemination (IUI) or natural intercourse were performed after either human chorionic gonadotropin (hCG)-induced or spontaneous, urinary luteinizing hormone (LH) surge-monitored ovulation. A total of 148 cycles were analyzed. In 40 cycles treated with hCG-induced ovulation and IUI, 3 (7.5%) patients conceived, whereas 37 women accomplished natural intercourse after hCG-induced ovulation and 2 (5.5%) became pregnant. When inseminated after a spontaneous LH surge, 3 (8.8%) of 34 patients achieved a pregnancy; no conception occurred in 37 spontaneously ovulatory cycles combined with timed intercourse. Pregnancy rates did not substantially differ between the treatment modalities or between mono-ovulatory and polyovulatory cycles. The cycle characteristics between spontaneous ovulatory and hCG-induced cycles significantly did differ.", "To examine the relative efficacies of leuprolide acetate (LA) and hCG in inducing ovulation and a normal luteal phase during clomiphene citrate (CC)-stimulated superovulation cycles.\n Prospective, randomized, blinded, and cross-controlled in consecutive cycles.\n Large military tertiary care center.\n Twenty-one ovulatory patients undergoing superovulation with CC and IUIs for the treatment of unexplained or male factor infertility.\n Clomiphene citrate (100 mg/d) on cycle days 5 through 9 in both of the study cycles. Administration of 2 mg SC LA in one cycle and 10,000 IU IM hCG in another cycle for induction of the midcycle surge.\n Serum LH, FSH, E2, and P levels every 12 hours for 36 hours after administration of either LA or hCG to characterize the midcycle hormonal dynamics. Luteal phase duration and serum P levels during the midluteal phase were used to estimate the adequacy of the luteal phase. Serial ultrasounds also were done to determine the incidence of luteinized unruptured follicle syndrome.\n Serum FSH levels in the periovulatory interval were significantly higher after the administration of LA. There were no differences in the periovulatory E2 or P levels or the incidence of sonographic evidence of ovulation after administration of either LA or hCG. Although midluteal serum P levels were higher in the cycles in which hCG was administered, all 42 treatment cycles had adequate luteal phases as assessed by luteal phase duration and three midluteal P levels. Ongoing pregnancies occurred after both LA- and hCG-stimulated cycles.\n Leuprolide acetate and hCG were equivalent in their abilities to induce ovulation. Further evaluation of the adequacy of the luteal phase and the ensuing pregnancy rates after LA induction of an endogenous gonadotropin surge are indicated.", "Forty-eight patients in a programme of intrauterine insemination (IUI) were randomized in a cross-over study. All were stimulated with clomiphene citrate (CC) and inseminated either after follicular rupture induced by human chorionic gonadotrophin (HCG) or after a spontaneous urinary luteinizing hormone (LH) surge. The HCG was administered when follicles of 18-22 mm in diameter were observed on ultrasound and IUI was performed 37-40 h thereafter. The monitoring of a urinary LH peak was carried out using a rapid urinary LH test. IUI took place approximately 22 h after detection of the LH surge. Overall, the pregnancy rates were 9.3% (4/43) after HCG induced ovulation and 20.5% (9/44) after spontaneous ovulation (P = 0.12). Analysis of mid-cycle events showed that following sonographic criteria, the HCG injection was performed significantly earlier in the cycle compared with the spontaneous LH surge. In addition, the mean diameter of the preovulatory follicles was significantly smaller and insemination was substantially earlier in the HCG induced cycles. These findings suggest that a beneficial effect arises from allowing the natural process of final follicular maturation to occur.", "To compare the in vivo effectiveness of recombinant (r) hCG with urinary (u) hCG during controlled ovarian hyperstimulation and intrauterine insemination (COH-IUI) cycles.\n Prospective controlled clinical study.\n Private IVF center.\n Two hundred eighty-four subjects undergoing COH-IUI cycles.\n Women were randomized into receiving r-hCG or u-hCG for final maturation and induction of ovulation.\n Clinical pregnancy rate and outcome of pregnancy.\n Background characteristics were similar in the two groups studied except for a slight difference in the mean duration of infertility (3.0 vs. 2.3). There was no significant difference in the number of follicles > or =16 mm, mean peak E(2), or mean 1-week P levels between the two groups. The clinical pregnancy rate was 27.1% in the recombinant group compared with 28.5% in the urinary group. The outcome of pregnancy was similar in both groups.\n Recombinant hCG was found to be as effective as u-hCG in achieving pregnancy during COH-IUI cycles. This is in agreement with earlier studies on the effectiveness of r-hCG in IVF cycles.", "To compare two methods of timing IUI, urinary LH monitoring and transvaginal ultrasonography/ hCG timing of ovulation, in patients receiving clomiphene citrate.\n Prospective, randomized, crossover study.\n Yale University Reproductive Medicine Center.\n Infertile couples undergoing IUI because of unexplained infertility, anovulation, or male factor infertility.\n Patients received clomiphene citrate on days 3-7 of the menstrual cycle and were randomized initially to one of two monitoring protocols. In protocol A, urinary LH monitoring was used to time IUI. Urinary LH levels were determined daily with the use of commercial kits, starting on day 10 of the cycle. When urinary LH was detected, IUIs were performed daily for the next 2 days. In protocol B, ultrasound monitoring of folliculogenesis was performed until a leading follicle of > or = 18 mm was noted, at which time hCG (10,000 IU) was given intramuscularly and IUIs were performed daily for the next 2 days. If no pregnancy occurred, the couple crossed over to the alternate protocol for the next cycle and continued this alternating therapy for a total of four cycles.\n Pregnancy rate per cycle.\n One hundred forty-one cycles were completed. In these cycles, six pregnancies occurred, for an overall pregnancy rate of 4.26% per cycle. The pregnancy rate with LH-timed IUI was 4.29% (3/70) and that with hCG-induced ovulation was 4.23% (3/71); the difference was not statistically significant.\n Timing IUI with the use of a relatively expensive and time-consuming method such as ultrasound monitoring of folliculogenesis and hCG induction of ovulation does not appear to produce an increased pregnancy rate over urinary LH monitoring of ovulation.", "To compare pregnancy rates with two different methods of intrauterine insemination (IUI) timing in patients treated with clomiphene citrate (CC).\n Prospective, randomized trial.\n Academic medical center.\n One hundred fifty ovulatory, infertile women.\n Patients were randomized into a luteinizing hormone (LH) surge group or a follicle monitoring/human chorionic gonadotropin (hCG) group. All patients underwent baseline ultrasound, and took clomiphene citrate, during days 5-9. Patients in the LH surge group underwent IUI on the day after a home test for the LH surge was positive, whereas those in the hCG group received hCG according to ultrasound parameters and underwent insemination 33-40 hours later. Patients remained in the same study group for up to three cycles.\n Pregnancy rates per cycle and per patient.\n No significant differences were found between groups in pregnancy rates per patient or per cycle. The LH surge group underwent IUI significantly later than the hCG group. Cancellation rates were significantly higher for the LH surge group (31% vs. 11%) and attributable mainly to failure to detect an LH surge. The majority of pregnancies in both treatment groups occurred in the first cycle.\n The decision to use hCG for IUI timing should be influenced by factors other than pregnancy rates." ]

[ "11991886", "16141015", "9922408", "16338507", "10919545", "12890374", "8625677", "10453854", "11858916", "16263999" ]

[ "The utility of albuterol nebulized with heliox during acute asthma exacerbations.", "Beneficial effects of albuterol therapy driven by heliox versus by oxygen in severe asthma exacerbation.", "Use of heliox-driven nebulizer therapy in the treatment of acute asthma.", "Albuterol nebulized in heliox in the initial ED treatment of pediatric asthma: a blinded, randomized controlled trial.", "Inhaled heliox does not benefit ED patients with moderate to severe asthma.", "Inhaling beta(2)-agonist with heliox-driven in bronchial asthma.", "Evaluation of heliox in children hospitalized with acute severe asthma. A randomized crossover trial.", "The effect of heliox in acute severe asthma: a randomized controlled trial.", "Prospective randomized trial of heliox-driven continuous nebulizers in the treatment of asthma in the emergency department.", "Helium/oxygen-driven albuterol nebulization in the treatment of children with moderate to severe asthma exacerbations: a randomized, controlled trial." ]

[ "Heliox improves lung deposition of inhaled particles when compared with air or oxygen inhalation. We studied the spirometric effects of albuterol nebulized with heliox during emergency room visits for asthma exacerbations. Forty-five patients were randomized to receive albuterol nebulized with oxygen (control) versus heliox (n = 22 control and 23 heliox subjects). At baseline, demographics, outpatient asthma medications, vital signs, oxygen saturation, and forced expiratory volume in one second were not different between the two groups. Three consecutive albuterol treatments were given to each group. The heliox group had a significantly higher heart rate after albuterol nebulization compared with the control group. Following albuterol Treatment 1, the median change in forced expiratory volume in one second was 14.6% in the control group and 32.4% in the heliox group (p = 0.007). After Treatment 2, the results were 22.7% versus 51.5%, respectively (p = 0.007). After Treatment 3, the results were 26.6% versus 65.1%, respectively (p = 0.016). We conclude that during acute asthma exacerbations, albuterol nebulized with heliox leads to a more significant improvement in spirometry when compared with albuterol nebulized with oxygen. This is likely due to the low-density gas improving albuterol deposition in the distal airways.", "To determine and define the beneficial effects of heliox-driven albuterol therapy on severe asthma exacerbation and clinical factors that affect greater response.\n The authors conducted two randomized, double-blinded, controlled trials in patients with severe asthma exacerbation. The first trial recruited 80 patients in the emergency department (ED). They received three consecutive doses of albuterol delivered by a nebulizer powered by either O(2) (O(2) group) or heliox (He/O(2) = 80:20; heliox group). Changes in peak expiratory flow rate (PEF) were compared, and factors influencing the response to heliox-driven albuterol therapy were identified. The second trial of 80 patients was conducted in older patients, a subpopulation associated with greater response in the first trial.\n In the first trial, the heliox group had more rapid and greater improvement in PEF compared with the O(2) group. There tended to be more patients in the heliox group reaching the predetermined dischargeable PEF (>60% predicted) after three albuterol treatments (odds ratio, 2.58; 95% confidence interval = 1.03 to 6.46; p = 0.069). For patients eventually discharged from the ED, the ED stay was shorter by 10 minutes per patient in the heliox group compared with the O(2) group (p = 0.007). Logistic regression showed older age and lower pretreatment PEF to be associated with favorable heliox responses. The second trial, which recruited older patients (older than 40 years), showed greater improvement in PEF and dyspnea score with heliox-driven albuterol therapy in patients with lower pretreatment PEF.\n Heliox-driven albuterol may be a useful adjunct therapy for older asthmatic patients with severe asthma exacerbation.", "To compare the effectiveness of a helium-oxygen mixture with that of oxygen alone as an aerosolizing gas for beta-agonist therapy in patients with mild to moderate exacerbation of asthma.\n A prospective, single-blinded study was performed in an urban teaching hospital over a period of 5 months. A convenience sample of 205 patients with mild to moderate exacerbation of asthma were enrolled. The participants were randomly assigned to 1 of 2 groups. The first group received 3 doses of albuterol, 5.0 mg aerosolized in 10 L/min of oxygen, 15 minutes apart. The second group received 3 doses of albuterol, 5.0 mg aerosolized in 10 L/min of a 70:30 helium-oxygen mixture (heliox), 15 minutes apart. Peak expiratory flow rate (PEFR), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1 ) were measured before and after each treatment. Only PEFR and FEV1 were used in data analysis.\n Although both the heliox and the oxygen group showed significant improvement in PEFR from baseline after 45 minutes (72% and 70%, respectively), the difference between the 2 groups was clinically and statistically insignificant (P =.56). Similar findings were observed for FEV1. There was no difference in rate of admission or rate of complications between the 2 groups.\n Despite its ability to decrease the turbulent flow in airways and to reach distal pulmonary tissues, heliox had no clinically significant advantage over standard therapy in the treatment of mild to moderate asthma. Further large-scale studies are necessary to determine the clinical efficacy of heliox in this setting.", "A prospective blinded, randomized controlled trial was undertaken to compare the initial response of albuterol nebulized in heliox or control in the treatment of moderately severe asthma in children presenting to a pediatric ED.\n Patients were randomized to receive heliox (n = 20) or control (n = 21). The primary outcome was to compare a modified dyspnea index score at 10 and 20 minutes after randomization. Secondary outcomes were to determine if heliox decreased admission rates or endotracheal intubation.\n There was no statistically significant difference found at 10 or 20 minutes after randomization with heliox (P = .169 and P = .062, respectively). No statistical difference in admission rate was found, and no patients required endotracheal intubation in either group.\n Our results demonstrate that albuterol nebulized with heliox offered no clinical benefit over standard therapy in the initial treatment of moderately severe asthma in the ED.", "nan", "To evaluate the effectiveness of a helium-oxygen mixture (79%He- 21%O(2)) as an aerosolizing compressed gas for beta(2)-agonist therapy in patients with an asthma exacerbation.\n Twenty-four patients in the outpatient department with a mild to moderate exacerbation of asthma were enrolled. The patients were randomly divided into an experimental group (13 cases) and a control group (11 cases). The experimental group inhaled Berotec with heliox-driven, and the control group inhaled Berotec with compressed air-driven. Eight hospitalized patients in the respiratory department with severe exacerbation of asthma were enrolled. The patients inhaled Berotec with heliox-driven or compressed air-driven in a random order.\n The results of spirometric parameters and arterial blood-gas analysis were measured. In the mild to moderate asthma patients, no statistical differences between the two groups for forced vital capacity (FVC), forced expired volume in one second (FEV(1)), and expiratory flow in 50% forced vital capacity (FEF(50)) were presented. But the severe patients showed significant differences between heliox-driven and compressed air-driven for FVC, FEV(1), FEF(50) and partial pressure of oxygen (PaO(2)).\n Compared with the traditional inhalation of beta(2)-agonist therapy using compressed air-driven, the method of inhaling beta(2)-agonist with heliox-driven has more obvious benefits for those suffering from severe asthma. This is likely due to the cooperative effects between inhaling heliox on its physical gas properties and improving delivery of beta(2)-agonist in the treatment of exacerbation of severe asthma.", "To determine whether breathing a blend of 70% helium:30% oxygen (heliox) would improve pulmonary function, decrease clinical score, and improve the sensation of dyspnea in children hospitalized with acute severe asthma.\n Prospective, randomized, double-blind, crossover study.\n The inpatient pediatric service of a military, tertiary care, teaching hospital.\n Children 5 to 18 years who required hospital admission for treatment of acute asthma.\n All patients received 5 mg of nebulized albuterol every 1 to 4 h, with a dose given within 30 min of the start of the study, and IV administered methylprednisolone. Patients breathed heliox and a 30% oxygen-enriched air mixture for 15 min each in random order.\n Clinical score, dyspnea score, oxygen saturation, heart rate, and respiratory rate, followed by FVC, FEV1, peak expiratory flow rate (PEFR), and, mean midexpiratory flow rate (FEF25-75) were obtained at study entry, 15 min after breathing the first gas mixture (heliox or air per randomization), 15 min after breathing the second mixture, and again 15 min after stopping the second gas mixture (study end values). Eleven children were enrolled, and all completed the study. There were no significant differences between study entry and study end spirometric values. Using the paired t test, we found no significant differences between mean values (SD) of FEV1 and FVC obtained while breathing heliox vs air; FEV1-heliox, 53% (18%) of the predicted value; FEV1-air, 52% (16%) of the predicted value (p = 0.36); FVC-heliox, 69% (22%) of the predicted value; and FVC-air, 70% (21%) of the predicted value (p = 0.50). The differences in values for PEFSR and FEF25-75 while breathing heliox vs air were small but did reach statistical significance in favor of heliox: PEFR-heliox, 56% (20%) of the predicted value; PEFR-air, 50% (16%) of the predicted value (p = 0.04); FEF25-75-heliox, 32% (13%) of the predicted value; and FEF25-75-heliox, 29% (11%) of the predicted value (p = 0.006). Heliox had no effect on either clinical or dyspnea scores.\n The short-term inhalation of heliox did not benefit this group of children hospitalized with acute, severe asthma.", "To evaluate the effect of heliox on airflow obstruction and dyspnea in patients with acute severe asthma.\n A prospective, randomized, controlled study.\n A university hospital.\n Twenty-three patients presenting to the emergency department with acute severe asthma were randomized to receive 70%/30% heliox or 30% oxygen.\n Peak expiratory flow (PEF), dyspnea score, heart rate, respiratory rate (RR), and BP were measured at baseline and 20, 120, 240, 360, and 480 min after starting the test gas. After baseline, the PEF was measured by using the gas that was randomized to the treatment program.\n In the first 20 min, there was a 58.4% increase in percent predicted PEF (%PEF) in the heliox group (p<0.001), whereas there was only a 10.1% increase in %PEF for the oxygen group (p>0.1). Eighty-two percent of the heliox group had >25% improvement in %PEF at 20 min, whereas only 17% of the oxygen group did (p<0.01). The next significant improvement in %PEF in the heliox group occurred at 480 min. At the end of the study in the heliox group, the PEF did not significantly (p>0.1) change immediately after the heliox was discontinued (270.6 to 264.2 L/min). In the heliox group in the first 20 min, there was a significant decrease in dyspnea score and RR (p<0.05), but there were no further significant improvements for the rest of the study. In the oxygen group, no variables significantly improved until 360 min.\n Heliox rapidly improves airflow obstruction and dyspnea in patients with acute severe asthma and may be useful as a therapeutic bridge until the corticosteroid effect occurs.", "The purpose of this study was to evaluate the efficacy of heliox-driven continuous nebulizers in the management of moderate to severe asthma exacerbations in the Emergency Department (ED). The trial was a prospective, randomized, double-blind, controlled trial in a university Emergency Department (volume 65,000 patients/year) of patients 18-55 years of age with acute asthma exacerbations. Patients were placed on continuous nebulizers driven by 70:30 heliox or air with 30% O(2). Respiratory rate, peak expiratory flow rate (PEFR), forced expiratory volume at 1 s (FEV1), and Borg dyspnea scale were measured at 0 and 2 h. Disposition and patient satisfaction were also assessed. A total of 36 patients completed the study (18 heliox, 18 air). There was no difference between groups in baseline variables. There was significant interval improvement within both groups at 2 h in PEFR, FEV1, Borg, and respiratory rate. There was no significant difference between heliox 70:30 and air/oxygen in PEFR [mean between-group improvement difference 17 liters/min, 95% confidence interval (CI) -20-51], FEV1 (0.03 liters/sec, 95% CI -0.22-0.30), or respiratory rate (mean between-group improvement difference 0.5, 95% CI -2.7-3.8). There was a significant improvement in the patients' perceived dyspnea as measured by the Borg dyspnea scale at 2 h in the heliox group (1.6, 95% CI 0.3-3.0). In this trial of patients with moderate-severe asthma exacerbation, heliox-driven continuous nebulizers failed to demonstrate an improvement in respiratory rate, oxygen saturation, PEFR, or FEV1 at 2 h. However, there was a significant improvement in the patients' perceived dyspnea on heliox over air/oxygen measured by the Borg dyspnea scale.", "Helium and oxygen mixtures (heliox) increase both pulmonary aerosol delivery and gas delivery relative to oxygen. We aimed to compare the effectiveness of a 70%:30% helium/oxygen (heliox)-driven continuous aerosol delivery versus 100% oxygen-driven delivery in the treatment of asthmatic children with moderate to severe exacerbations.\n We enrolled 30 children aged 2 to 18 years who presented to an urban, pediatric emergency department (ED) with moderate to severe asthma as defined by a pulmonary index (PI) score of > or =8. PI scores can range from 0 to 15. In this randomized, controlled, single-blind trial conducted in a convenience sample of children, all patients in the trial received an initial nebulized albuterol (5 mg) treatment driven by 100% oxygen and a dose of oral prednisone or prednisolone. Subsequently, patients were randomly assigned to receive continuously nebulized albuterol (15 mg/hour) delivered by either heliox or oxygen using a nonrebreathing face mask. The primary outcome measure was degree of improvement as assessed in blinded video-recorded PI scores over 240 minutes (at 30-minute intervals for the first 3 hours) or until ED discharge (if <240 minutes).\n The mean change in PI score from baseline to 240 minutes or ED discharge was 6.67 for the heliox group compared with 3.33 for the oxygen group. Eleven (73%) patients in the heliox group were discharged from the hospital in <12 hours compared with 5 (33%) patients in the conventional group.\n Continuously nebulized albuterol delivered by heliox was associated with a greater degree of clinical improvement compared with that delivered by oxygen among children with moderate to severe asthma exacerbations." ]

[ "8425695", "3169499", "2184355" ]

[ "Cyclosporin A treatment in primary biliary cirrhosis: results of a long-term placebo controlled trial.", "Pilot study of cyclosporin A in patients with symptomatic primary biliary cirrhosis.", "A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis." ]

[ "Effective treatment for primary biliary cirrhosis (PBC) resulting in slower progression and improved survival remains elusive. Cyclosporin A (CyA), which has been so effective in preventing human allograft rejection, has shown promise in small numbers of patients in early studies.\n Three hundred forty-nine patients with PBC were randomized to receive CyA, 3 mg.kg-1.day-1, or placebo in a multicenter study with follow-up for 6 years. The end point was death or liver transplantation.\n Cox multivariate analysis showed time from entry to death or transplantation was significantly prolonged (by up to 50%) in the CyA-treated group. Liver-related mortality was also significantly lower. However, a univariate analysis of survival showed no statistical differences between the two groups. Biochemical liver indices deteriorated more slowly in the CyA-treated group, but serum creatinine concentration was elevated > 150 mumol/L in 9%, necessitating permanent discontinuation in half of these. A reduction in the dose of CyA was required in 11% because of hypertension.\n CyA has some therapeutic potential in primary biliary cirrhosis, providing blood pressure and renal function are closely monitored.", "The purpose of this pilot study was to determine whether daily administration of cyclosporin A to symptomatic patients with primary biliary cirrhosis for 1 yr would lead to a significant and sustained improvement in liver enzyme abnormalities. Twelve adult patients (11 female, 1 male; aged 52.6 +/- 8.9 yr, mean +/- SD) with serologic and histologically defined primary biliary cirrhosis were randomized to receive either oral cyclosporin A or vehicle placebo. Cyclosporin A was administered at sufficient dosages to maintain serum radioimmunoassay trough levels between 100 and 200 ng/ml (starting dosage, 2.5 mg/kg.day). After 1 yr of therapy, significant changes from pretreatment values were seen only in recipients of cyclosporin A. These included a 37% decrease in mean serum alkaline phosphatase and a 43% decrease in gamma-glutamyltransferase (controls +3% and -14%, respectively). Mean serum bilirubin and albumin levels and prothrombin times remained unaltered in the two groups, as did the extent of inflammation and fibrosis and the histologic staging of liver biopsy specimens. Although mean serum creatinine levels increased by 51% in recipients of cyclosporin A (+2% in controls), there were no associated changes in diastolic blood pressure or creatinine clearance values. Other side effects including thrombocytopenia, hirsutism, headaches, tremor, and parasthesiae were common in the treated group but not of sufficient severity to warrant adjustment in the dosage or discontinuation of therapy. The observed changes in hepatic, renal, and hematologic tests tended to return to baseline after discontinuation of therapy. Two patients, both placebo recipients, died of liver failure during the study period. The results of this study indicate that in symptomatic primary biliary cirrhosis, cyclosporin A administration is associated with a significant improvement in cholestatic liver enzyme abnormalities that persists for the duration of therapy. A progressive rise in serum creatinine levels and a high incidence of side effects raise concerns regarding the long-term safety of this agent in primary biliary cirrhosis.", "Primary biliary cirrhosis is a progressive disease of the liver characterized by the immunologic destruction of bile ducts; effective therapy is lacking. We therefore evaluated the safety and efficacy of low-dose cyclosporine in 29 patients with primary biliary cirrhosis without evidence of damage to the lobular architecture (precirrhotic disease) or portal hypertension. The patients were randomly assigned to receive either cyclosporine (4 mg per kilogram of body weight per day) or placebo. After one year 17 of the 19 patients assigned to cyclosporine had improvement or stability in their degree of fatigue, and 18 in their degree of pruritus. In contrast, among the 10 patients assigned to placebo, fatigue increased in 4 (P less than 0.06) and pruritus worsened in 6 (P less than 0.001). Those assigned to cyclosporine also had significant decreases in serum levels of bilirubin, alanine aminotransferase, alkaline phosphatase, gamma globulin, and the titer of antimitochondrial antibodies. For the 20 patients who have completed two years in the study, liver biopsies (coded specimens) showed evidence of histologic progression in only 1 of 13 patients in the cyclosporine group, as compared with 5 of 7 in the placebo group (P less than 0.003). No patient has permanently discontinued cyclosporine because of side effects; however, signs of nephrotoxicity developed in 12 of 19, and 9 of 19 had increased blood pressure. We conclude that in patients with precirrhotic primary biliary cirrhosis, immunosuppressive therapy with cyclosporine is promising and deserves further evaluation." ]

[ "12812689", "11315832", "8846745", "15089797", "17049662", "15569128", "9219407", "11815494", "15510531" ]

[ "[Group versus individual education for type-2 diabetes patients].", "Comprehensive evaluation of community-based diabetic patients: effect of feedback to patients and their physicians: a randomized controlled trial.", "The relative effectiveness of educational and behavioral instruction programs for patients with NIDDM: a randomized trial.", "Long-term effects of self-management education for patients with Type 2 diabetes taking maximal oral hypoglycaemic therapy: a randomized trial in primary care.", "Effectiveness of lifestyle counseling by certified expert nurse of Japan for non-insulin-treated diabetic outpatients: a 1-year randomized controlled trial.", "Effects of a structured health education programme by a diabetic education nurse on cardiovascular risk factors in Chinese Type 2 diabetic patients: a 1-year prospective randomized study.", "One-to-one teaching with pictures--flashcard health education for British Asians with diabetes.", "Assessment of group versus individual diabetes education: a randomized study.", "A nurse-coaching intervention for women with type 2 diabetes." ]

[ "To compare the effectiveness of group (GE) and individual (IE) health education in type-2 diabetes patients, and identify the improvement in knowledge, metabolic control and risk factors.\n Randomised clinical trial.\n Primary care.Participants. 68 patients with type-2 diabetes, diagnosed 6 months before the start of the study and who had not received GE. Patients aged over 75, those with sensory, psychological and/or physical deficiencies and those not monitored in primary care were excluded (alpha=0.05; beta=0.2).Interventions. Patients were selected according to the inclusion criteria and allocated at random to the IE (n=33) or GE (n=35) group. Individual and group lessons were given at the same time for a year. The contents were evaluated with a validated, self-administered test.\n General, demographic variables, analyses, blood pressure, the Body Mass Index (BMI), the presence of cardiovascular risk factors, diabetes-related complications and therapeutic variables were all measured.\n The two kinds of education showed no significant differences from each other. The two groups improved the level of knowledge (P<0.001), and reduced HbA1c (P<0.001), HDL-C (P<0.001), the BMI (P=0.001) and systolic pressure (P=0.004), and increased their use of reactive strips (P=0.02).\n Health education on diabetes improved knowledge of the disease, metabolic control and cardiovascular risk factors. The two educational methods evaluated were equally effective.", "To demonstrate improvements in diabetes care stimulated by comprehensive evaluation of community-based diabetic patients with feedback to the patients and their physicians.\n A comprehensive evaluation of community-based diabetic patients with annotated reporting of results to both patients and their physicians (universal intervention) was followed by random assignment of 50% of patients to individual counseling (randomized intervention). In four communities, two large and two small, 55 type 1 and 376 type 2 diabetic patients were recruited, evaluated, and reassessed at 1 year. Outcome measures were HbA1c, serum cholesterol, and systolic and diastolic blood pressure.\n There were significant improvements in all outcome measures for type 2 diabetic patients randomized to individual counseling (P = 0.03; follow-up rate 84%) and significant improvements in all outcome measures for all high-risk type 2 patients (highest P value = 0.004; follow-up rate 85%).\n Comprehensive evaluation of diabetic patients at the community level with annotated reporting of results to the patients and their physicians was associated with improvement of mean HbA1c, cholesterol, and systolic and diastolic blood pressure, particularly in patients in high-risk status for these outcome variables. Individual counseling of 50% of patients, randomly selected, enhanced these results.", "In this randomized trial patients with non-insulin-dependent diabetes were allocated to one of four programs: a minimal instruction program (n = 59), and education program of individual visits (n = 57), an education program incorporating a group education course (n = 66), and a behavioral program (n = 59). Individual and group education programs had higher attrition rates than the behavioral and minimal programs. The four programs, which involved different amounts of patient contact time, delivery format, and instructional strategies, all produced reductions in HbA1 and BMI, with no significant differences between the programs. There were no differences between groups over three time periods in total cholesterol, HDL cholesterol, systolic blood pressure, or proportion of patients consulting an ophthalmologist. The behavioral program produced a greater reduction in diastolic blood pressure over 12 months than the education programs and a greater reduction in the cholesterol risk ratio over 3 months than the other programs. The behavioral program patients were more likely to have visited a podiatrist after 6 months and reported higher satisfaction.", "Education is an essential part of the management of patients with Type 2 diabetes, but the long-term effects are unclear and not well investigated in primary care.\n Fifty-four patients (39-75 years) treated with maximal dosages of oral hypoglycaemic agents, needing to start insulin (HbA(1c)> or = 7.0%), were randomly allocated to a 6-month educational programme by a diabetes nurse (DN group) or usual care (UC group). Main outcome measures were HbA(1c), number of patients with HbA(1c) < 7.0%, and number of patients treated with insulin 18 months after baseline.\n Six weeks after the intervention HbA(1c) levels had improved from 8.2 (1.1) to 7.2 (1.3) in the DN group, and from 8.8 (1.5) to 8.4 (1.7) in the UC group. Adjusted for baseline values, at 6 weeks HbA(1c) improved 0.7% (95% confidence interval 0.1, 1.4) more in DN than in UC. Of the patients in DN, 60% reached HbA(1c) < 7.0% compared with 17% in UC (P < 0.01). However, at 18 months there were no significant differences for HbA(1c), number of patients with HbA(1c) < 7.0%, or number treated with insulin.\n Education was effective in improving glycaemic control and in delaying the need for insulin therapy in patients treated with maximal oral hypoglycaemic therapy. The reduced effect after 1 year was probably due to the discontinuation of the educational programme. Short-term education should not be offered without regular reinforcements integrated into standard diabetes care.", "We examine whether one-to-one lifestyle counseling for non-insulin-treated diabetic outpatients by a Certified Expert Nurse (CEN) can improve patients' health outcomes. Participants were randomly assigned to a 1-year lifestyle intervention (n=67) or to a usual care group (n=67). Main outcome measures were changes from baseline in: HbA(1C) and score of health related quality of life scales (SF-36 and Problem Areas in Diabetes Scale). Cognitive/behavioral modification for 1 year and satisfaction in CEN counseling was also measured by self-produced items. We found no significant differences in HbA(1C), BMI, blood pressure, serum lipids, or health related quality of life over 1 year between the two groups. Patients in the intervention group, however, showed modest but more favorable modification of cognition (p=0.004) and behavior (p<0.001) than subjects in usual care group. The low attrition rate (9%), more frequent hospital visit (12+/-2 times versus 11+/-3 times; p=0.03) and high degree of satisfaction (95%) in the intervention group indicate feasibility of the monthly CEN counseling in the outpatient settings of Japanese hospitals. Future research should confirm the long-term effectiveness of the CEN counseling on clinical outcomes and the cost effectiveness of a possibly time-consuming intervention.", "To assess the effect of regular diabetic health education on cardiovascular risk factors in Chinese Type 2 diabetic patients.\n This was a 1-year prospective randomized study. One hundred and eighty Type 2 diabetic subjects were recruited from three regional diabetic centres in Hong Kong. Ninety received additional structured reinforcement of diabetic health education by a trained nurse after the doctors' consultations every 3 months (intervention group). The others received the same medical care except no nursing reinforcement (control group). Outcome measures included fasting plasma glucose, HbA(1c), body mass index, waist circumference, blood pressure and lipid profiles, which were assessed before the study and after 1 year.\n Two of the controls defaulted follow-up. The intervention group and controls had similar age and sex distribution. At the end of study, the intervention group had reducted their waist circumference, diastolic blood pressure, HbA(1c), total cholesterol and low-density lipoprotein cholesterol levels. The controls had reduced their total cholesterol and low-density lipoprotein cholesterol levels. Other cardiovascular risk factors were not significantly changed in the controls. Addition of drugs and/or dosage increment of anti-diabetic drugs, lipid-lowering agents and anti-hypertensive agents were similar between the two groups.\n Regular structured reinforcement with diabetic health education is useful. It helps to control more successfully some of the cardiovascular risk factors in Chinese Type 2 diabetic patients.", "Type 2 diabetes is up to four times more common in British Asians, but they know little about its management and complications.\n To design and evaluate a structured pictorial teaching programme for Pakistani Moslem patients in Manchester with type 2 diabetes.\n A randomized controlled trial of pictorial flashcard one-to-one education in 201 patients attending a hospital outpatient clinic or diabetic clinics in ten general practices in Manchester. Patients' knowledge, self-caring skills and attitudes to diabetes were measured on four topics before the structured teaching, and compared with results six months later.\n All parameters of knowledge were increased in the study group; for example, percentage scores for correctly identifying different food values increased from 57% to 71% (Analysis of Variance (ANOVA) adjusted difference +11.8%) and knowledge of one diabetic complication from 18% to 78%. Self-caring behaviour improved, with 92% of patients doing regular glucose tests at six months compared with 63% at the start. Attitudinal views were more resistant to change, with patients still finding it hard to choose suitable foods at social occasions. Haemoglobin A1c control improved by 0.34% over six months (ANOVA adjusted difference, 95% CI -0.8% to +0.1%).\n It is concluded that this health education programme can empower Asian diabetics to take control of their diets, learn to monitor and interpret glucose results, and understand the implications of poor glycaemic control for diabetic complications.", "The current study was conducted to compare the effectiveness of delivering diabetes education in either a group or individual setting using a consistent, evidence-based curriculum.\n A total of 170 subjects with type 2 diabetes were randomly assigned to either group (n = 87) or individual (n = 83) educational settings. Subjects received education in four sequential sessions delivered at consistent time intervals over a 6-month period. Outcomes included changes in knowledge, self-management behaviors, weight, BMI, HbA(1c), health-related quality of life, patient attitudes, and medication regimen. Changes were assessed at baseline and after the 2-week, 3-month, and 6-month education sessions.\n Both educational settings had similar improvements in knowledge, BMI, health-related quality of life, attitudes, and all other measured indicators. HbA(1c) decreased from 8.5 +/- 1.8% at baseline to 6.5 +/- 0.8% at 6 months (P < 0.01) in the study population as a whole. Subjects assigned to the individual setting had a 1.7 +/- 1.9% reduction in HbA(1c) (P < 0.01), whereas subjects assigned to the group setting had a 2.5 +/- 1.8% reduction in HbA(1c) (P < 0.01). The difference in HbA(1c) improvement was marginally greater in subjects assigned to group education versus individualized education (P = 0.05).\n This study demonstrates that diabetes education delivered in a group setting, when compared with an individual setting, was equally effective at providing equivalent or slightly greater improvements in glycemic control. Group diabetes education was similarly effective in delivering key educational components and may allow for more efficient and cost-effective methods in the delivery of diabetes education programs.", "The purpose of this pilot study was to determine the efficacy of a 6-month nurse-coaching intervention that was provided after diabetes education for women with type 2 diabetes.\n In this pilot study, 53 women were randomized to the nurse-coaching intervention or a standard care control condition. The nurse-coaching intervention consisted of 5 individualized sessions and 2 follow-up phone calls over 6 months. The nurse-coaching sessions included educational, behavioral, and affective strategies. Data were collected on physiologic adaptation (hemoglobin A1c [A1C] and body mass index [BMI]), self-management (dietary and exercise), psychosocial adaptation (diabetes-related distress and integration), and treatment satisfaction at baseline, 3 months, and 6 months.\n Women in the treatment group demonstrated better diet self-management, less diabetes-related distress, better integration, and more satisfaction with care, and had trends of better exercise self-management and BMI. The A1C levels improved in both groups at 3 months, yet the difference between the groups was not significant. Attendance at nurse-coaching sessions was 96%.\n This nurse-coaching intervention demonstrates promise as a means of improving self-management and psychosocial outcomes in women with type 2 diabetes." ]

[ "11198566", "12220097", "16629842", "8868708", "18728909" ]

[ "Underemployment and depression: longitudinal relationships.", "Marginal employment and health in Britain and Germany: does unstable employment predict health?", "Evaluation of an open-rota system in a Danish psychiatric hospital: a mechanism for improving job satisfaction and work-life balance.", "Individual flexibility: an essential prerequisite in arranging shift schedules for midwives.", "Effects of shift rotation and the flexibility of a shift system on daytime alertness and cardiovascular risk factors." ]

[ "We conceptualize employment status not as a dichotomy of working versus not working but as a continuum ranging from adequate employment to inadequate employment (involuntary part-time or low wage) to unemployment. Will shifts from adequate to inadequate employment increase depression as do shifts from employment to unemployment, and to what extent does prior depression select workers into such adverse employment change? We analyze panel data from the National Longitudinal Survey of Youth for the years 1992-1994 for the 5,113 respondents who were adequately employed in 1992. Controlling for prior depression, both types of adverse employment change resulted in similar, significant increases in depression. These direct effects persisted despite inclusion of such potential mediators as changes in income, job satisfaction, and marital status. Marital status buffered the depressive effect of both types of adverse change, but education and job dissatisfaction amplified the effect of unemployment on depression. Prior depression did not predict higher risk of becoming inadequately employed but did predict increased risk of unemployment, particularly for those with less education. These results confirm that both unemployment and inadequate employment affect mental health, and they invite greater efforts to monitor the extent and impact of underemployment.", "This study examines the possible health impact of marginal employment, including both temporary and part-time employment schemes. It addresses three research questions: (1) Are employed people with a fixed-term contract or no contract more likely to report poor health than those who hold jobs with permanent contracts? (2) Are part-time employed respondents (even when they hold jobs with permanent contracts) more likely to report poor health than full-time workers? (3) Does change in employment stability (i.e., from employment with permanent contract to fixed-term or no contract employment and vice-versa) have an impact on health status? Logistic regression models were used to analyze panel data from Britain and Germany (1991-1993), available in the Household Panel Comparability Project data base. We included 10,104 respondents from Germany and 7988 from Britain. A single measure of perceived health status was used as the dependent variable. Controlling for background characteristics, the health status of part-time workers with permanent contracts is not significantly different from those who are employed full-time. In contrast, fulltime employed people with fixed-term contracts in Germany are about 42 per cent more likely to report poor health than those who have permanent work contracts. In Britain, only part-time work with no contract is associated with poor health, but the difference is not statistically significant. We conclude that monitoring the possible health effects of the increasing number of marginal employment arrangements should be given priority on the social welfare research agenda.", "To evaluate the impact of an open-rota scheduling system on the health, work-life balance and job satisfaction of nurses working in a psychiatric ward in Denmark.\n The effects of shift rotation and scheduling are well known; however, little is known about the wider benefits of open-rota systems. Method A structured questionnaire was distributed to control and intervention groups preintervention and postintervention (20 months). Nurses within the intervention group trialed an open-rota system in which nurses designed their own work-rest schedules.\n Nurses in the intervention group reported that they were more satisfied with their work hours, less likely to swap their shift when working within the open-rota system and reported significant increases in work-life balance, job satisfaction, social support and community spirit when compared with nurses in the control groups.\n The ownership and choice over work-rest schedules has benefits for nurses, and potentially the hospital.", "The irregular shift system in Finnish hospitals with schedules traditionally planned for short 3-week periods creates problems in the social life of the personnel. Current backward rotation with 'quick returns' and rest periods between the shifts which are too short cause fatigue. The possibilities provided by legislation for individual and functional flexibility in the planning of schedules have not been utilized because of the hierarchical structure of hospital organizations. This study was aimed at finding measures to reduce the strain caused by irregular shift work. It consisted of two parts: a survey of midwives doing a three-shift work in hospitals (n = 366), and an intervention in six maternity wards (n = 45). During the 6-month intervention the influence potential of the personnel increased, and the number of quick returns fell. As a result, the mental strain of the work decreased and the stress levels fell. The positive effects were evident especially among the elderly midwives: their work became less strenous and their social interaction improved. Despite the positive effects of the intervention, 55% preferred the former system with longer continuous free time. The physiological criteria for a good shift system were outweighed by the demands of social life, emphasizing the importance of individual flexibility and participation in the planning process.", "A controlled intervention study was conducted to evaluate the effects of two changes in shift characteristics on alertness and cardiovascular risk factors: a change in shift rotation (direction and speed) and a change in the flexibility of the shift system.\n Altogether 84 male workers currently working in a backward-rotating shift system volunteered for the study. A total of 40 men changed to a rapidly forward-rotating shift system, 22 changed to a more flexible shift system, and 22 remained with the old shift system. Health effects were studied with the use of clinical measurements, blood tests, and questionnaires before and after the shift changes. Analyses of variance were used with repeated measures to study associations of cardiovascular risk factors and daytime sleepiness according to the change in shift systems.\n The mean number of days on which the workers reported sleepiness decreased in the group with the forward-rotating shift system when compared with that of the group on the old shift system (from 2.9 to 2.1 days/week, P=0.02). Systolic blood pressure decreased (from 142 to 136 mm Hg, P=0.049), and heart rate showed a declining trend (from 66 to 60 beats/minute, P=0.06) in the flexible shift system when the three groups were compared.\n The study indicates that a faster speed, together with a change to the forward direction, in shift rotation alleviates daytime sleepiness. Combining individual flexibility with company-based flexibility in a shift system may have favorable effects on shift workers' blood pressure." ]

[ "7976095", "17966531", "9521027", "12846911", "8245265", "3105681", "20110630", "15121121", "15009297", "15871318", "9767241", "15086765" ]

[ "Vein surgery with or without skin grafting versus conservative treatment for leg ulcers. A randomized prospective study.", "The influence of surgical treatment for chronic leg ulcers on the quality dynamics of the patient's life.", "Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group.", "An autologous epidermal equivalent tissue-engineered from follicular outer root sheath keratinocytes is as effective as split-thickness skin autograft in recalcitrant vascular leg ulcers.", "Randomized trial comparing cryopreserved cultured epidermal allografts with hydrocolloid dressings in healing chronic venous ulcers.", "Pinch skin grafting or porcine dermis in venous ulcers: a randomised clinical trial.", "Wound stimulation by growth-arrested human keratinocytes and fibroblasts: HP802-247, a new-generation allogeneic tissue engineering product.", "Treatment of venous leg ulcers with Dermagraft.", "Cryopreserved and lyophilized cultured epidermal allografts in the treatment of leg ulcers: a pilot study.", "Tapping into the influence of keratinocyte allografts and biocenosis on healing of chronic leg ulcers: split-ulcer controlled pilot study.", "Treatment of venous leg ulcers with cryopreserved cultured allogeneic keratinocytes: a prospective open controlled study.", "Autologous cultured keratinocytes on porcine gelatin microbeads effectively heal chronic venous leg ulcers." ]

[ "In order for us to evaluate the efficiency of perforator vein surgery and skin grafting in leg ulcer patients, 47 patients were randomized into 3 treatment groups (group A: surgery for incompetent perforators, group B: surgery for incompetent perforators and ulcer excision followed by grafting, group C: control group). All the patients were treated with a compression bandage. When cellulitis was observed, a systemic antibiotic was given; eczema was treated with a steroid ointment. Fourty patients were evaluated regularly during one year after entry. There were no differences between the 3 treatment groups considering base-line characteristics, median ulcer size at entry and after one year. According to a review of the initial phlebograms, the occurrence of post-thrombotic changes in the deep veins were recorded in the majority of the legs. Our results suggest that ligation of incompetent perforators and skin grafting, as used in the present study, may not offer an additional advantage for venous ulcer patients with insufficiency of the deep veins when compared to conservative treatment. However, the removal of insufficient superficial veins was not studied.", "This study was undertaken to assess the effectiveness of skin grafting and the influence on the quality of the lives of patients who have large chronic venous ulcers.\n We have performed the perspective analysis of the course of the disease and of treatment results after 6 months. Two groups of patients were involved in the study. Group O contains patients who have been treated by performing skin graft surgery, while group C contains patients who have been treated only by conservative means. All patients studied have been treated during the period of 2001-2005 at the Department of Plastic Surgery and Burns and at the Clinic of Skin and Venereal Diseases (CSVD) of Kaunas Medical University Hospital (KMUH). During the visit patients had to complete a questionnaire (enclosed with patient's history of treatment), according to which we evaluated the influence of large chronic venous leg ulcers on the quality of patients' lives. This questionnaire has been developed in accordance with the questionnaire for the evaluation of quality of life prepared by prof. dr. M. E. Hyland.\n At the beginning of the study all patients of O and C groups suffered from pain in the legs. However, at the end of the study, pain decreased only in patients of O group (p < 0.05), while in C group pain practically remained the same. At the beginning of the study, the ulcers deprived many patients from both groups of sleep for most of the night (37-41%). During the repeated questioning it turned out that ulcers only deprived 2.5% of patients in group O of sleep for most of the night, whereas in group C this rose to 19.35%.\n Skin grafting positively influences the quality of patients' lives significantly (p < 0.05). Skin grafting has decreased the limitation of function and improved the dysphoric mood. The coverage of ulcers by autografts of skin thickness, had decreased the leg pain within 6 months, significantly more than by conservative treatment alone (p < 0.05). The amount of patients' personal expenditure on the care and treatment of ulcers, increased within the period of 6 months for 11.2% of patients in whom large CVUL were treated conservatively. The amount of personal expenses decreased to 12.8% of patients in whom skin grafting was applied (p > 0.05).", "To test the safety, efficacy, and immunological impact of a cultured allogeneic human skin equivalent (HSE) in the treatment of venous ulcers.\n Prospective, randomized study.\n Multicenter study in the outpatient setting.\n Each patient with a venous ulcer received either compression therapy alone or compression therapy and treatment with HSE. The patients were evaluated for HSE safety, complete (100%) ulcer healing, time to wound closure, wound recurrence, and immune response to the HSE.\n The study was completed as planned in 293 randomized patients.\n Treatment with HSE was more effective than compression therapy in the percentage of patients healed by 6 months (63% vs 49%; P=.02, Fisher exact test, 2-tailed) and the median time to complete wound closure (61 days vs 181 days; P=.003, log-rank test). Treatment with HSE was superior to compression therapy in healing larger (> 1000 mm2; P=.02) and deeper ulcers (P=.003) and ulcers of more than 6 months' duration (P=.001). Occurrence of adverse events was similar in both groups. No symptoms or signs of rejection occurred in response to treatment with HSE, and no HSE-specific immune responses were detected in vitro to bovine collagen or to alloantigens expressed on keratinocytes or fibroblasts.\n Treatment with HSE healed venous ulcers more rapidly and in more patients than compression therapy alone. There was no clinical or laboratory evidence of rejection or sensitization in response to HSE application. These data suggest that HSE represents a significant advance in the treatment of venous ulcers, particularly those that are difficult to heal.", "The outer root sheath of hair follicles plays an important role in epidermal regeneration in vivo. Keratinocytes isolated by explantation of outer root sheath tissue have extensive proliferative capacity irrespective of donor age, which probably depends on pluripotent epithelial stem cells residing in the outer root sheath. These keratinocytes can be organotypically grown to epidermal equivalents in vitro. We report here that in a multicenter, randomized phase II study, EpiDex trade mark, a tissue-engineered, fully differentiated autologous epidermal equivalent derived from keratinocytes of the outer root sheath of plucked anagen hair follicles, is as effective as split-thickness skin autografting in the promotion of healing and complete closure of recalcitrant vascular leg ulcers.", "Cultured epidermal allografts have been successfully used to treat a variety of wounds. Their postulated mechanism of action is through release of cytokines that stimulate epithelialization. On the basis of previous experience we expected ulcers treated with cryopreserved cultured allografts (CCAs) to be healed by 6 weeks. Hydrocolloid dressings (HCDs) have also been reported to be effective in the treatment of venous ulcers.\n Our purpose was to compare the effectiveness of CCAs with HCDs in healing chronic venous ulcers.\n Forty-three patients with 47 ulcers were enrolled in a randomized controlled trial. Ulcers not healed by 6 weeks were changed to the other treatment.\n No difference in the number of healed ulcers between the two groups was observed at 6 weeks. Healing rate, percent reduction of initial ulcer size, and radial progression toward wound closure were significantly greater for CCAs than for HCDs. Pain relief was not significantly different.\n CCAs achieve more rapid healing and greater reduction in ulcer size than HCDs.", "Chronic venous ulcers are common, and even with effective compression or elevation large ulcers may take months to heal. Pinch skin grafting may allow healing from epithelial islands throughout the surface area of the ulcer, and a prospective randomised trial was therefore conducted comparing this treatment with porcine dermis dressings. Most patients were treated as outpatients, 25 ulcers being randomised to treatment with pinch skin grafts and 28 to treatment with porcine dermis. Though the groups were well matched, the mean healing rate in the first week was 15 cm2 for pinch skin grafts compared with 3.5 cm2 with porcine dermis (p less than 0.02). By life table analysis 64% of ulcers treated by pinch grafts were healed at six weeks and 74% by 12 weeks compared with 29% and 46% of ulcers, respectively, treated with porcine dermis dressings (chi2 = 4.1; p less than 0.05). All ulcers that failed to heal within 12 weeks included an area posterior to the medial malleolus, where local compression may have been inadequate. Pinch skin grafting improves the rate of healing in large venous ulcers and is a simple technique that may be performed as an outpatient procedure under local anaesthesia.", "HP802-247 is a new-generation, allogeneic tissue engineering product consisting of growth-arrested, human keratinocytes (K) and fibroblasts (F) delivered in a fibrin matrix by a spray device.\n To identify the preferred dose of HP802-247 based on cell concentration and K/F ratio.\n A multicenter, randomized, double-blind, placebo-controlled, explorative phase II study of 6 different doses of HP802-247 administered once per week for 12 consecutive weeks in chronic venous leg ulcers.\n HP802-247 was safe and well tolerated and showed increasing efficacy dependent on cell concentration and K/F ratio, in line with in vitro growth factor release data. The mean complete closure rate at week 12 for all patients treated with HP802-247 was 40%, and for placebo it was 33%. In contrast to placebo, all HP802-247 dose groups improved from week 12 to 24.\n As an integral part of a rational tissue engineering product development, this explorative trial identified the preferred dose of HP802-247 for further clinical studies.", "A number of different treatment approaches have been recommended for the treatment of venous ulceration, including local ulcer treatment, compression and drug therapy. Recent advances in tissue engineering have resulted in living tissues being developed for cutaneous wound repair and skin replacement. The aim of this pilot study was to compare the rate of healing of venous ulcers in patients treated with Dermagraft (a human fibroblast-derived dermal replacement) and compression therapy or compression therapy alone.\n A total of 18 patients with venous ulceration of the leg were recruited into the pilot study. Ten patients were treated with Dermagraft and compression therapy, and eight patients were treated with compression therapy alone. Healing was assessed by ulcer tracing and computerised planimetry. Skin perfusion was measured by laser Doppler.\n Five (50%) of the patients treated with Dermagraft and one (12.5%) control patient had healed by the end of the 12-week study period (NS). The total ulcer area rate of healing and linear rate of healing was significantly improved in patients treated with Dermagraft (P=0.001 and P=0.006, respectively, Mann-Whitney U-test). The number of capillaries increased in both the treatment and control group. Peri-ulcer skin perfusion increased by 20% in patients treated with Dermagraft, compared with 4.9% in the control group.\n The data from this small pilot study suggests that Dermagraft is associated with improved healing of venous ulceration. Following this pilot study, further clinical studies are needed to confirm the validity of these results in 'hard to heal' venous leg ulcers.", "In the conservative therapy of venous leg ulcers modern types of dressings are used most frequently. In the past 20 years 'active wound dressings' - cultured epidermal keratinocytes as autografts and allografts - were also introduced in the management of leg ulcers.\n The aim of our study was to compare the effect of cryopreserved and lyophilized cultured epidermal allografts in the treatment of venous leg ulcers. Evaluation of the therapy was documented as photodocumentation, planimetry, healing time and evaluation of pain relief over a 3-month period after application. Fifty patients with venous leg ulcers were selected. Twenty-five patients (group I) were treated with cryopreserved keratinocytes and 25 (group II) with lyophilized keratinocytes.\n The final evaluation 3 months after the application of allografts showed 84% of healed ulcers in group I and 80% in group II. The number of healed ulcers and the healing rate both showed no statistically significant differences. The size of the ulcer was reduced by half during the first week in both groups. The size differences during the first week are statistically significant in both groups and they are comparable (P < 0.001). The intensity of the pain was statistically significantly reduced during the first week after application in both groups (P < 0.001).\n The cryopreserved and lyophilized cultured allografts are comparable in healing rate, course of healing and relief of pain, and also in planimetric changes during the healing of venous leg ulcers. Lyophilized allografts are more convenient for routine use than cryopreserved allografts as they can be stored at room temperature. These results could give rise to the more frequent use of lyophilized allografts in slow-healing venous leg ulcers.", "Cultured keratinocytes may represent an alternative therapy aiming at boosting leg ulcer healing. There is no evidence-based study comparing objectively the healing rate of split-ulcer portions covered or not covered by cultured keratinocytes.\n To assess the effect of cultured keratinocytes on the healing rate of leg ulcers.\n Five applications of fresh (cela, XCELLentis, Ghent, Belgium) or frozen (CryoCeal, XCELLentis) cultured allogeneic keratinocytes were performed at weekly intervals to treat large leg ulcers (mean diameter > 5 cm) in four patients. A split-ulcer study was designed to secure a control area covered only by petrolatum gauze. Clinical, planimetric, bacteriologic, and immunohistologic assessments of the keratinocyte-treated and control parts of the ulcers were performed.\n Compared with controls, planimetry revealed a beneficial effect afforded by cryopreserved cultured keratinocytes on the ulcer healing rate of two of four ulcers (+12 and 81%). The healing effect was obtained on the ulcers associated with the lowest bacterial load. Cultured keratinocytes did not qualitatively and quantitatively modify the ulcer biocenosis. They did not affect the number of any type of inflammatory cells present in the granulation tissue (type I dermal dendrocytes, macrophages, T lymphocytes, granulocytes). No specific side effect of cultured keratinocytes was evidenced.\n In this small case series, it appears that cultured allogeneic keratinocytes may be helpful in the healing process of venous leg ulcers. However, a clean wound with reduced bacterial load seems to be the prerequisite condition for obtaining a beneficial effect.", "Twenty-seven patients with chronic venous leg ulcers were assigned to two treatment groups. Fifteen were treated with cryopreserved cultured allogeneic keratinocyte sheets and compression bandages and 12 with compression only. The observation time was 8 weeks and the keratinocyte grafting procedure was performed once weekly. The mean reduction of the initial wound area was 35% in the treatment group and 14% in the control group. This difference was not significant. The poor effect on wound healing given by the cryopreserved allogeneic keratinocyte sheets contrasts with our earlier experience using fresh keratinocyte sheets. We believe that this is due to a weakened condition of the cryostored cells, as we have shown a loss in protein synthesis capacity of at least 50%.", "We have established a specific bioreactor microcarrier cell culture system using porcine gelatin microbeads as carriers to produce autologous keratinocytes on a large scale. Moreover, we have shown that autologous keratinocytes can be cultured on porcine collagen pads, thereby forming a single cell layer. The objective of this study was to compare efficacy and safety of autologous cultured keratinocytes on microbeads and collagen pads in the treatment of chronic wounds. Fifteen patients with recalcitrant venous leg ulcers were assigned to three groups in a single-center, prospective, uncontrolled study: five underwent a single treatment with keratinocyte monolayers on collagen pads (group 1); another five received a single grafting with keratinocyte-microbeads (group 2); and the last five received multiple, consecutive applications of keratinocyte-microbeads 3 days apart (group 3). All patients were followed for up to 12 weeks. By 12 weeks, there was a mean reduction in the initial wound area of 50, 83, and 97 percent in the three groups, respectively. The changes in wound size were statistically significant between the first and third groups (p= 0.0003). Keratinocyte-microbeads proved to be more effective than keratinocyte monolayers on collagen pads when the former were applied every 3 days. Rapid availability within 10-13 days after skin biopsy and easy handling represent particular advantages." ]

[ "15749490", "11232790", "9757895", "9457946" ]

[ "Effect of sperm treatment with exogenous platelet-activating factor on the outcome of intrauterine insemination.", "Comparative study on efficacy of three sperm-separation techniques.", "A randomized comparison of the methods of sperm preparation for intrauterine insemination.", "A randomized, prospective analysis of five sperm preparation techniques before intrauterine insemination of husband sperm." ]

[ "To evaluate the effect of sperm treatment with exogenous platelet-activating factor (PAF) on IUI clinical pregnancy rate.\n Prospective randomized study.\n Assisted Reproduction Unit, 2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Athens, Greece.\n Fifty-two couples with unexplained infertility, candidates for IUI.\n Sperm treatment with an exogenous mixture of PAF (final concentration, 10(-7) mol/L) in sperm-washing medium, direct swim-up technique of sperm preparation, a maximum of six IUI cycles per couple with or without PAF treatment.\n Clinical pregnancy rate (pregnancies confirmed by ultrasonography per hundred cycles).\n The overall clinical pregnancy rate after a maximum of six IUI cycles was significantly higher when sperm was treated with PAF compared with the rate after the direct swim-up technique (23.07% vs. 7.92%).\n Treatment of sperm with exogenous PAF might improve the clinical outcome of IUI in cases of unexplained infertility.", "To evaluate the comparative effectiveness of real-time sperm separation technique (Wang's tube method) and other two conventional methods in isolating high-quality sperm preparation, and to compare the spouse pregnancy rate in intrauterine insemination (IUI) with sperm preparations isolated by these methods.\n The effectiveness of the real-time sperm separation technique, the conventional swim-up and the Percoll discontinuous density gradient methods in isolating sperm preparations from 60 infertile patients (20 with apparently normal semen and 40, abnormal semen contaminated with microorganisms and other impurities) was evaluated and compared. The microorganisms to be removed included bacteria, virus, Chlamydia trachomaticum, Ureaplsama urealyticum, etc. The spouse pregnancy rates in IUI with sperm preparations isolated by these three techniques from 80 oligoasthenoteratospermic patients were also compared.\n The quality (including the percentages of normal form, normal-chromatin and motile sperm, and the grade of motility) of sperm obtained by the real-time sperm separation technique was much higher (P < 0.01) as compared with those by the other two methods. The Wang's tube method was also more effective in removing microorganisms and other impurities. The method provided a higher IUI pregnancy rate than the other two sperm separation techniques (P < 0.05).\n The real-time sperm separation technique is the most effective method so far available in isolating high-quality sperm samples to be used in assisted reproduction.", "To compare the effectiveness of three methods of sperm preparation for IUI during superovulation of infertile women.\n Randomized assignment of one of three sperm preparation methods.\n University infertility practice.\n Infertile couples undergoing superovulation and IUI.\n The method of preparation of sperm for IUI during superovulation was assigned randomly to double centrifugation, multiple-tube swim-up, or Percoll density gradient.\n Total number and percent recovery of motile sperm, percent of recovered sperm with normal morphology, and cycle fecundity.\n No method of sperm preparation provided better cycle fecundity than the others despite differences in sperm recovery.\n Double centrifugation, multiple-tube swim-up, and Percoll density gradient sperm preparation for IUI yield similar cycle fecundity rates.", "To evaluate pregnancy rates (PRs) in women undergoing artificial insemination with sperm alternately prepared by one of five techniques: sperm washing, Percoll gradient centrifugation, swim-up, swim-down, or refrigeration/heparin treatment.\n Each treatment group alternated in a different order through the five sperm preparations. Pregnancy rates were compared for each sperm preparation.\n Two infertility centers, one located in an academic institution and the other a regional hospital.\n Three hundred sixty-three women undergoing 898 artificial inseminations with husband semen with a progressive motile sperm count of >20 million sperm per mL were randomly placed in the five treatment groups.\n Pregnancy rates.\n The overall ongoing PR per insemination was 9.7% (87/898), including 6.12% for natural cycles (n = 196), 12.8% for clomiphene citrate-stimulated cycles (n = 101), and 10.3% for gonadotropin-stimulated cycles (n = 601). The highest ongoing PRs for sperm preparations followed the swim-up technique (13.2%, 26/197) and the Percoll gradient centrifugation technique (12.7%, 26/204).\n These data suggest that the swim-up and Percoll gradient preparations result in higher PRs than the wash, swim-down, and refrigeration/heparin techniques." ]

[ "1918559", "11026946", "8995042", "8871794", "7568536" ]

[ "Marital therapy as a treatment for depression.", "The London Depression Intervention Trial. Randomised controlled trial of antidepressants v. couple therapy in the treatment and maintenance of people with depression living with a partner: clinical outcome and costs.", "Spouse-aided therapy with depressed patients.", "Individual behavioural-cognitive therapy v. marital therapy for depression in maritally distressed couples.", "A comparison of two modalities of cognitive therapy (individual and marital) in treating depression." ]

[ "The purpose of this study was to compare cognitive-behavioral therapy (CT; n = 20), behavioral marital therapy (BMT; n = 19), and a treatment combining BMT and CT (CO; n = 21) in the alleviation of wives' depression and the enhancement of marital satisfaction. BMT was less effective than CT for depression in maritally nondistressed couples, whereas for maritally distressed couples the two treatments were equally effective. BMT was the only treatment to have a significant positive impact on relationship satisfaction in distressed couples, whereas CO was the only treatment to enhance the marital satisfaction of nondistressed couples. On marital interaction measures CO was the only treatment to significantly reduce both husband and wife aversive behavior and to significantly increase wife facilitative behavior.", "Relapse of depression is associated with a criticising attitude of the patient's partner.\n To compare the relative efficacy and cost of couple therapy and antidepressant drugs for the treatment and maintenance of people with depression living with a critical partner.\n A randomised controlled trial of antidepressant drugs v. couple therapy. The subjects were 77 people meeting criteria for depression living with a critical partner.\n Drop-outs were 56.8% [corrected] from drug treatment and 15% from couple therapy. Subjects' depression improved in both groups, but couple therapy showed a significant advantage, according to the Beck Depression Inventory, both at the end of treatment and after a second year off treatment. Adding the costs of the interventions to the costs of services used showed there was no appreciable difference between the two treatments.\n For this group couple therapy is much more acceptable than antidepressant drugs and is at least as efficacious, if not more so, both in the treatment and maintenance phases. It is no more expensive overall.", "Twenty-three non-maritally distressed depressed patients who were married or cohabitating were randomly assigned to either individual behavioral-cognitive therapy or spouse-aided treatment. Both treatment conditions focused on depressed mood, behavioral activity, and dysfunctional cognitions, the difference being that in the spouse-aided treatment the partner was involved in all aspects of treatment, whereas in the individual condition the partner was not involved. MANOVAs revealed that treatment led to statistically significant improvement on depressed mood, behavioral activity, and dysfunctional cognitions. Treatment did not affect relationship variables (marital satisfaction, communication, and expressed emotion) for both spouses. Spouse-aided therapy was as effective as individual cognitive-behavior therapy.", "Depressed patients are often characterised by marital distress, but few studies investigate the effects of marital therapy on depressed mood and relationship dysfunction.\n Twenty-seven depressed patients experiencing marital distress were randomly assigned to either individual behavioural-cognitive therapy or marital therapy. The individual treatment condition focused on depressed mood, behavioural activity and dysfunctional cognitions, whereas in the marital condition the partner was involved in the treatment and the focus was on the communication process in the marital relationship. MANOVAs revealed that treatment led to statistically significant improvements in depressed mood, behavioural activity and dysfunctional cognitions, an increase in relationship satisfaction and improvement of communication in patients and spouses. A significant interaction effect was found, showing that marital therapy had more impact on relationship variables than the individual treatment.\n Both individual cognitive-behaviour therapy and marital therapy lead to less depressive complaints, and both treatment conditions have a positive effect on the relationship, although the effect on the relationship is significantly stronger in couples who were tested by marital therapy compared with patients who were treated individually.", "Historically, depression was explained and treated intrapsychically and/or biochemically. In the 1970s theoretical propositions and treatment applications began to appear that offered that depression should be viewed cognitively (Beck 1963, 1974; Beck et al. 1979) or interpersonally (Coyne 1976a, 1976b; Klerman et al. 1984). Simultaneously, though more sporadically, marital interventions started to attract interest (Feldman 1976; Friedman 1975). The cognitive and interpersonal trends of thinking stimulated researchers to investigate the efficacy of these therapeutic modalities and to compare them with each other. Interest in these two treatments peaked with the publication of the study that emerged from the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program (Elkin et al. 1989). This well-known research found that the two psychotherapies were similarly effective, but that the interpersonal approach was slightly more successful with more severely depressed patients." ]

[ "17400858" ]

[ "Surgical treatments for vulvar and vaginal dysplasia: a randomized controlled trial." ]

[ "To compare pain, adverse effects and recurrence of dysplasia in patients with vaginal intraepithelial neoplasia or vulvar intraepithelial neoplasia prospectively treated by carbon dioxide laser or ultrasonic surgical aspiration.\n Patients were randomly assigned to receive treatment by laser or ultrasonic surgical aspiration from 2000-2005. Preoperative biopsy was done to confirm presence of dysplasia. Patients completed a visual analog scale regarding pain and were evaluated at 2-4 weeks to assess scarring, wound healing, and adverse effects. Patients returned every 3 months for 1 year for pelvic examination and cytology to assess recurrence. Follow-up colposcopy and biopsy were used at the discretion of the treating physician. Student t test, chi2, analysis of variance and multiple logistic regression were used for analysis.\n One hundred ten patients were randomly assigned. Ninety-six (87.3%) patients completed 1 year follow-up. Mean age of patients was 48.5 years. Mean visual analog scale score was significantly lower in patients treated by ultrasonic surgical aspiration (20.7 compared with 35.1; P=.032). For patients with vulvar lesions, there was less scarring with ultrasonic surgical aspiration (P<.01). Recurrence overall was 25% and was similar for ultrasonic surgical aspiration compared with laser (relative risk 0.96, 95% confidence interval 0.64-1.50, number needed to treat 95.6). Recurrence was associated with younger age (P<.01).\n Patients treated with ultrasonic surgical aspiration for vulvar and vaginal dysplasia reported less postoperative pain. Vulvar scarring was more common in patients treated by the laser. There was no difference in recurrence of dysplasia during a 1-year follow-up period between the two surgical modalities.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00394758\n I." ]

[ "11459333", "2189869", "8657838", "15129422", "2648867", "11343529", "12547477", "15641864", "11910265", "16892419", "11729013", "11534876", "15118483", "10770145", "2407208", "10621763", "7814344", "9160600", "9160569", "15378676", "10331117", "10907802", "14608246", "11775045", "2051152", "12356658", "3406235" ]

[ "Olanzapine in the treatment of post-traumatic stress disorder: a pilot study.", "Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment.", "A double-blind, randomized, placebo-controlled, multi-center study of brofaromine in the treatment of post-traumatic stress disorder.", "Comparison of nefazodone and sertraline for the treatment of posttraumatic stress disorder.", "A controlled trial of desipramine in 18 men with posttraumatic stress disorder.", "Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder.", "Mirtazapine vs. placebo in posttraumatic stress disorder: a pilot trial.", "A preliminary study of risperidone in the treatment of posttraumatic stress disorder related to childhood abuse in women.", "Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder.", "A controlled trial of paroxetine for chronic PTSD, dissociation, and interpersonal problems in mostly minority adults.", "Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study.", "Sertraline, paroxetine, and venlafaxine in refugee posttraumatic stress disorder with depression symptoms.", "A placebo-controlled study of nefazodone for the treatment of chronic posttraumatic stress disorder: a preliminary study.", "Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial.", "Treatment of posttraumatic stress disorder with amitriptyline and placebo.", "Fluoxetine in post-traumatic stress disorder. Randomised, double-blind study.", "Fluoxetine in posttraumatic stress disorder.", "Inositol treatment of post-traumatic stress disorder.", "Pharmacotherapy of post-traumatic stress disorder with a novel psychotropic.", "Efficacy and tolerability of mirtazapine and sertraline in Korean veterans with posttraumatic stress disorder: a randomized open label trial.", "A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder.", "Lack of efficacy for fluoxetine in PTSD: a placebo controlled trial in combat veterans.", "Can physiologic assessment and side effects tease out differences in PTSD trials? A double-blind comparison of citalopram, sertraline, and placebo.", "Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial.", "Pharmacotherapy for posttraumatic stress disorder using phenelzine or imipramine.", "Fluoxetine v. placebo in prevention of relapse in post-traumatic stress disorder.", "A controlled trial of phenelzine in posttraumatic stress disorder." ]

[ "Because the atypical antipsychotic olanzapine may be efficacious in treating post-traumatic stress disorder (PTSD) symptoms, we conducted a 10-week, double-blind, placebo-controlled evaluation in which 15 patients were randomized 2:1 to either olanzapine or placebo. The initial dosage was 5 mg/day and was titrated to a maximum of 20 mg/day. Eleven patients completed the study. Patients in both groups showed improvement in PTSD symptoms, but no between-group differences in treatment response were observed and a high placebo response rate was found. Both treatments were tolerated well, although the olanzapine treatment group had more weight gain. Olanzapine fared no better than placebo in this preliminary study in the treatment of PTSD. The lack of difference between olanzapine and placebo may in part be due to olanzapine's not being effective in PTSD or, alternatively, a small sample size, a high placebo response in certain forms of PTSD and the chronicity of PTSD symptoms in some patients.", "The authors report a random-assignment, double-blind crossover trial comparing alprazolam and placebo in posttraumatic stress disorder (PTSD). Ten patients fulfilling DSM-III criteria for PTSD completed 5 weeks of treatment on each agent. Improvement in anxiety symptoms was significantly greater during alprazolam treatment but modest in extent. Symptoms specific to PTSD were not significantly altered. The impact of nonspecific symptomatic effects on the outcome of drug trials in PTSD is considered.", "A large multi-center, double-blind, parallel trial to assess the efficacy of brofaromine in the treatment of post traumatic stress disorder (PTSD) failed to show a significant difference between the brofaromine and placebo treatment groups. The placebo response rate in this study was higher than that in previously published double-blind, placebo-controlled studies of PTSD.", "Posttraumatic stress disorder (PTSD) is a prevalent condition that has been shown to be responsive to pharmacotherapy. Few head-to-head comparisons of medications used in the treatment of PTSD have been published. This 12-week, randomized, double-blind study compares the effectiveness, safety, and tolerability of nefazodone and sertraline for the treatment of PTSD. Thirty-seven male and female outpatients meeting DSM-IV criteria for PTSD were randomly assigned to receive nefazodone (maximum dose 600 mg/day; average dose 463 mg/day) or sertraline (maximum dose 200/day; average dose 153 mg/day). The primary outcome measures were the 17-item total severity score of the Clinician Administered PTSD Scale, Part 2 (CAPS-2) and the Clinical Global Impression Improvement Scale (CGI-I). Other assessments included the Davidson Trauma Scale (DTS), the Top-8 PTSD Rating Scale, Sheehan Disability Scale (SDS), Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (HAM-A), and Pittsburgh Sleep Quality Index (PSQI). Twenty-six subjects had at least one post-randomization CAPS-2 assessment and were therefore included in the data analysis. There were no statistically significant differences between treatment groups on any of the outcome measures. There was a significant effect for time in both groups, indicating an improvement in PTSD symptoms, depression, sleep, and quality of life over time. CAPS-2 scores for all of the PTSD symptom clusters decreased significantly over time. This study did not find significant differences in the effectiveness of nefazodone and sertraline for the treatment of PTSD. Larger trials are warranted.\n Copyright 2004 Wiley-Liss, Inc.", "Eighteen male U.S. veterans meeting DSM-III criteria for posttraumatic stress disorder (PTSD) completed a 4-week double-blind, crossover study comparing administration of 200 mg/day of desipramine with placebo. Response was measured by using the Beck Depression Inventory, the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, and the Impact of Event Scale. Overall, the only apparent response to desipramine was in some symptoms of depression; there were no changes in anxiety and other PTSD symptoms.", "Posttraumatic stress disorder (PTSD) is a common illness associated with significant disability. Few large, placebo-controlled trials have been reported.\n Outpatients with a DSM-III-R diagnosis of moderate-to-severe PTSD were randomized to 12 weeks of double-blind treatment with either sertraline (N = 100) in flexible daily doses in the range of 50 to 200 mg or placebo (N = 108). Primary outcome measures consisted of the Clinician-Administered PTSD Scale (CAPS-2) total severity score, the patient-rated Impact of Event Scale (IES), and the Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I) ratings.\n Mixed-effects analyses found significantly steeper improvement slopes for sertraline compared with placebo on the CAPS-2 (t = 2.96, P =.003), the IES (t = 2.26, P =.02), the CGI-I score (t = 3.62, P<.001), and the CGI-S score (t = 4.40, P<.001). An intent-to-treat end-point analysis found a 60% responder rate for sertraline and a 38% responder rate for placebo (chi(2)(1) = 8.48, P =.004). Sertraline treatment was well tolerated, with a 9% discontinuation rate because of adverse events, compared with 5% for placebo. Adverse events that were significantly more common in subjects given sertraline compared with placebo consisted of insomnia (35% vs 22%), diarrhea (28% vs 11%), nausea (23% vs 11%), fatigue (13% vs 5%), and decreased appetite (12% vs 1%).\n The results of the current study suggest that sertraline is a safe, well-tolerated, and significantly effective treatment for PTSD.", "Based on an earlier pilot study, as well as a theoretical consideration of its mechanism of action, we undertook a placebo-controlled, double-blind trial of mirtazapine in posttraumatic stress disorder.\n Twenty-nine patients were randomized to receive drug up to 45 mg/day or placebo double-blind on a 2:1 ratio for 8 weeks, with data being available for analysis in 26. Primary outcome measures comprised the Short Posttraumatic Stress Disorder Rating Interview (SPRINT) Global Improvement item and total score. Secondary measures comprised the Davidson Trauma Scale, Structured Interview for Posttraumatic Stress Disorder and Hospital Anxiety Depression Scale. Adverse events were also measured.\n On the Short Posttraumatic Stress Disorder Rating Interview Global Improvement measure, rates of response were 64.7% and 20.0% for mirtazapine and placebo. Treatment effects in favor of mirtazapine were noted on the Short Posttraumatic Stress Disorder Rating Interview global, Structured Interview for Posttraumatic Stress Disorder, and Hospital Anxiety Depression Scale anxiety subscale scores. The drug was well tolerated.\n Mirtazapine was more effective than placebo on some measures in posttraumatic stress disorder and general anxiety symptoms.", "This study evaluated the effectiveness of risperidone in women for the treatment of posttraumatic stress disorder (PTSD) related to childhood physical, sexual, verbal, and emotional abuse.\n Subjects were outpatient adult women, aged 18 to 64 years, with chronic PTSD related to childhood physical, sexual, verbal, or emotional abuse. Data were collected from November 18, 2001, to June 7, 2003. Subjects met DSM-III-R criteria for PTSD and criteria for PTSD on the Clinician-Administered PTSD Scale, 1-month version (CAPS-1). Subjects were randomly assigned to receive risperidone (N = 12) in flexible daily dosages in the range of 0.5 to 8 mg or placebo (N = 9) for 8 weeks. The primary outcome measures were changes in score from baseline on the CAPS-1 and the Clinician-Administered PTSD Scale, 1-week version (CAPS-2).\n Risperidone-treated patients had a significantly greater reduction in total score on the CAPS-2 (z = -2.44, p = .015). Risperidone-treated patients also had significantly greater reductions in the intrusive (z = -5.71, p < .001) and hyperarousal (z = -2.74, p = .006) subscale scores of the CAPS-2.\n The results of the current study indicate that low-dosage risperidone is a safe and effective treatment for intrusive and hyperarousal symptoms in adult women with chronic PTSD from childhood physical, sexual, verbal, and emotional abuse.", "The efficacy of sertraline in the treatment of civilian posttraumatic stress disorder (PTSD) has been established by two large placebo-controlled trials. The purpose of the current pilot study was to obtain preliminary evidence of the efficacy of sertraline in military veterans suffering from PTSD. Outpatient Israeli military veterans with a DSM-III-R diagnosis of PTSD were randomized to 10 weeks of double-blind treatment with sertraline (50-200 mg/day; N = 23, 83% male, mean age = 41 years) or placebo (N = 19, 95% male, mean age = 38 years). Efficacy was evaluated by the Clinician-Administered PTSD Scale (CAPS-2) and by Clinical Global Impression Scale-Severity (CGI-S) and -Improvement (CGI-I) ratings. Consensus responder criteria consisted of a 30% or greater reduction in the CAPS-2 total severity score and a CGI-I rating of \"much\" or \"very much\" improved. The baseline CAPS-2 total severity score was 94.3 +/- 12.9 for sertraline patients, which is notably higher than that reported for most studies of civilian PTSD. On an intent-to-treat endpoint analysis, sertraline showed a numeric but not statistically significant advantage compared with placebo on the CAPS-2 total severity and symptom cluster scores. In the study completer analysis, the mean CGI-I score was 2.4 +/- 0.3 for sertraline and 3.4 +/- 0.3 for placebo (t = 2.55, df = 30, p = 0.016), CGI-I responder rates were 53% for sertraline and 20% for placebo (chi2 = 3.62, df = 1, p = 0.057), and combined CGI-I and CAPS-2 responder rates (>or=30% reduction in baseline CAPS-2 score) were 41% for sertraline and 20% for placebo (chi2 = 1.39, df = 1, p = 0.238). Sertraline treatment was well tolerated, with a 13% discontinuation rate as a result of adverse events. This pilot study suggests that sertraline may be an effective treatment in patients with predominantly combat-induced PTSD, although the effect size seems to be somewhat smaller than what has been reported in civilian PTSD studies. Adequately powered studies are needed to confirm these results and to assess whether continued treatment maintains or further improves response.", "This study evaluated the efficacy of paroxetine for symptoms and associated features of chronic posttraumatic stress disorder (PTSD), interpersonal problems, and dissociative symptoms in an urban population of mostly minority adults. Adult outpatients with a primary DSM-IV diagnosis of chronic PTSD received 1 week of single-blind placebo (N = 70). Those not rated as significantly improved were then randomly assigned to placebo (N = 27) or paroxetine (N = 25) for 10 weeks, with a flexible dosage design (maximum 60 mg by week 7). Significantly more patients treated with paroxetine were rated as responders (14/21, 66.7%) on the Clinical Global Impression-Improvement Scale (CGI-I) compared to patients treated with placebo (6/22, 27.3%). Mixed effects models showed greater reductions on the Clinician-Administered PTSD Scale (CAPS) total score (primary plus associated features of PTSD) in the paroxetine versus placebo groups. Paroxetine was also superior to placebo on reduction of dissociative symptoms [Dissociative Experiences Scale (DES) score] and reduction in self-reported interpersonal problems [Inventory of Interpersonal Problems (IIP) score]. In a 12-week maintenance phase, paroxetine response continued to improve, but placebo response did not. Paroxetine was well tolerated and superior to placebo in ameliorating the symptoms of chronic PTSD, associated features of PTSD, dissociative symptoms, and interpersonal problems in the first trial conducted primarily in minority adults.", "This study evaluated the efficacy and safety of paroxetine for the treatment of patients with chronic posttraumatic stress disorder (PTSD).\n Outpatients with chronic PTSD according to DSM-IV criteria and a score of 50 or more on the Clinician-Administered PTSD Scale, part 2, were randomly assigned to take placebo (N=186), 20 mg/day of paroxetine (N=183), or 40 mg/day of paroxetine (N=182) for 12 weeks. Efficacy was assessed by examining the change in total score from baseline to endpoint on the Clinician-Administered PTSD Scale, part 2, and rates of response (\"very much improved\" or \"much improved\") for global improvement on the Clinical Global Impression scale.\n Paroxetine-treated patients in both dose groups demonstrated significantly greater improvement on primary outcome measures compared to placebo-treated patients in the intent-to-treat analysis. Moreover, paroxetine treatment resulted in statistically significant improvement compared to placebo on all three PTSD symptom clusters (reexperiencing, avoidance/numbing, and hyperarousal), social and occupational impairment, and comorbid depression. Paroxetine was effective for both men and women. Treatment response did not vary by trauma type, time since trauma, or severity of baseline PTSD or depressive symptoms. Both doses were well tolerated.\n Doses of 20 and 40 mg/day of paroxetine are effective and well tolerated in the treatment of adults with chronic PTSD.", "Three new antidepressants were used in treating posttraumatic stress disorder (PTSD) and symptoms of depression in Bosnian refugees. Thirty-two Bosnian refugees seeking treatment at a mental health clinic participated in a case series study. All received open trials of Sertraline (n = 15), Paroxetine (n = 12), or Venlafaxine (n = 5), with standard clinical doses. Overall, Sertraline and Paroxetine produced statistically significant improvement at 6 weeks in PTSD symptom severity in depression, and in Global Assessment of Functioning. Venlafaxine produced improvement in PTSD symptom severity and in Global Assessment of Functioning, did not yield improvement in symptoms of major depressive disorder; and had a high rate of side effects. Notwithstanding improvement of symptoms, all 32 refugees remained PTSD positive at the diagnostic level at the 6-week follow-up.", "Nefazodone is a unique serotonergic antidepressant that acts as both a presynaptic serotonin reuptake inhibitor and a postsynaptic 5-hydroxytryptamine 2A receptor antagonist. Based on the positive results of open-label trials of nefazodone, including one from our group, we tested nefazodone's efficacy in the treatment of posttraumatic stress disorder (PTSD) under placebo-controlled conditions. Forty-one patients with chronic PTSD, predominantly male combat veterans, were enrolled in a randomized, double-blind, placebo-controlled 12-week trial of nefazodone. The primary outcome measure was the Clinician-Administered PTSD Scale. Fifteen patients were randomized to placebo and 26 were randomized to nefazodone. In a repeated-measures analysis of variance with last observation carried forward, patients on nefazodone showed a significant improvement in the percentage change of Clinician-Administered PTSD Scale Total score from baseline compared with those on placebo (P = 0.04; effect size = 0.6). Sample size was not powered to test group differences in the Clinician-Administered PTSD Scale criterion B, C, or D subscale. However, the criterion D subscale showed significant improvement in patients treated with nefazodone compared with those treated with placebo (P = 0.007). In addition, the Hamilton Rating Scale for Depression showed significant improvement compared with placebo (P = 0.008). The nefazodone group also reported an improvement on the PTSD Checklist (self-report scale; P = 0.08) and the Clinician-Administered Dissociative States Scale (P = 0.06). This pilot study supports the efficacy of nefazodone for the treatment of PTSD. However, larger placebo-controlled studies in more diverse patient population are warranted.", "Despite the high prevalence, chronicity, and associated comorbidity of posttraumatic stress disorder (PTSD) in the community, few placebo-controlled studies have evaluated the efficacy of pharmacotherapy for this disorder.\n To determine if treatment with sertraline hydrochloride effectively diminishes symptoms of PTSD of moderate to marked severity.\n Twelve-week, double-blind, placebo-controlled trial preceded by a 2-week, single-blind placebo lead-in period, conducted between May 1996 and June 1997.\n Outpatient psychiatric clinics in 8 academic medical centers and 6 clinical research centers.\n A total of 187 outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity score of at least 50 at baseline (mean age, 40 years; mean duration of illness, 12 years; 73% were women; and 61.5% experienced physical or sexual assault).\n Patients were randomized to acute treatment with sertraline hydrochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week at 25 mg/d (n=94); or placebo (n=93).\n Baseline-to-end-point changes in CAPS-2 total severity score, Impact of Event Scale total score (IES), and Clinical Global Impression-Severity (CGI-S), and CGI-Improvement (CGI-I) ratings, compared by treatment vs placebo groups. Results Sertraline treatment yielded significantly greater improvement than placebo on 3 of the 4 primary outcome measures (mean change from baseline to end point for CAPS-2 total score, -33.0 vs -23.2 [P =.02], and for CGI-S, -1.2 vs -0.8 [P=.01]; mean CGI-I score at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score, showing a trend toward significance (mean change from baseline to end point, -16.2 vs -12.1; P=.07). Using a conservative last-observation-carried-forward analysis, treatment with sertraline resulted in a responder rate of 53% at study end point compared with 32% for placebo (P=.008, with responder defined as >30% reduction from baseline in CAPS-2 total severity score and a CGI-I score of 1 [very much improved], or 2 [much improved]). Significant (P<.05) efficacy was evident for sertraline from week 2 on the CAPS-2 total severity score. Sertraline had significant efficacy vs placebo on the CAPS-2 PTSD symptom clusters of avoidance/numbing (P=.02) and increased arousal (P=.03) but not on reexperiencing/intrusion (P=.14). Sertraline was well tolerated, with insomnia the only adverse effect reported significantly more often than placebo (16.0% vs 4.3%; P=.01).\n Our data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD.", "Amitriptyline hydrochloride was compared with placebo in 46 veterans with chronic posttraumatic stress disorder. Treatment continued up to 8 weeks, and efficacy was measured by five observer and two self-rated scales. Percent recovery rates were higher for amitriptyline than placebo on two measures. In patients who completed 4 weeks (n = 40), better outcome with amitriptyline was noted on the Hamilton depression scale only. In the group completing 8 weeks of treatment (n = 33), the drug was superior to placebo on Hamilton depression, Hamilton anxiety, Clinical Global Impression severity, and Impact of Event scales. There was no evidence for drug effects on the structured interview for posttraumatic stress disorder. Drug-placebo differences were greater in the presence of comorbidity in general, although recovery rates were uniformly low in the presence of major depression, panic disorder, and alcoholism. At the end of treatment, 64% of the amitriptyline and 72% of the placebo samples still met diagnostic criteria for posttraumatic stress disorder.", "Most pharmacotherapy trials in post-traumatic stress disorder (PTSD) have been conducted upon male combat veterans. Outcome studies relating to civilians are therefore needed.\n To demonstrate that fluoxetine is more effective than placebo in treating PTSD.\n Civilians with PTSD (n = 53) were treated for 12 weeks with fluoxetine (up to 60 mg/day) or placebo. Assessments of PTSD severity, disability, stress vulnerability, and high end-state function were obtained.\n Fluoxetine was more effective than placebo on most measures at week 12, including global improvement (much or very much improved: fluoxetine 85%, placebo 62%, difference 0.24, 95% CI 0.01-0.47; very much improved: fluoxetine 59%, placebo 19%, difference 0.40, 95% CI 0.16-0.64), and high end-state function (fluoxetine 41%, placebo 4%, difference 0.37, 95% CI 0.17-0.57).\n Fluoxetine was superior for measures of PTSD severity, disability, stress vulnerability, and high end-state function. The placebo-group response was low when viewed as a broad outcome based on a portfolio of ratings, but was higher with a traditional global rating criterion.", "This study was designed to establish the efficacy of the serotonin reuptake blocker fluoxetine in the treatment of posttraumatic stress disorder (PTSD).\n 64 subjects (22 women and 42 men; 31 veterans and 33 nonveterans) with PTSD entered a 5-week randomized double-blind trial comparing fluoxetine (N = 33) and placebo (N = 31).\n By Week 5 fluoxetine, but not placebo, significantly reduced overall PTSD symptomatology, as assessed by the Clinician-Administered PTSD Scale (CAPS) score. Changes were most marked in the arousal and numbing symptom subcategories. Non-VA patients responded much better than VA patients. Fluoxetine was an effective antidepressant independent of its effects on PTSD.\n Fluoxetine is an effective pharmacotherapeutic agent for treating PTSD and its associated features, particularly in patients without chronic treatment histories.", "nan", "This was a multicenter, randomized, double-blind, parallel trial conducted in outpatients in three countries. Following screening and placebo washout, patients received brofaromine (a combined MAO-A inhibitor/5-HT transport inhibitor) or placebo in a flexible dosing design. Based upon the CAPS, a standardized post-traumatic stress disorder (PTSD) interview, findings from a cohort involving both subchronic and chronic traumatic stress marginally favored brofaromine over placebo; however, not to a statistically significant degree. With a more conservation definition of the syndrome, employing a primary cohort of patients with PTSD of one year or greater duration, brofaromine significantly reduced PTSD symptoms in comparison with placebo. In all analyses a substantial proportion of patients in both drug and placebo groups remained symptomatic throughout. Findings were supported by an analysis of secondary measures. Brofaromine may be of benefit in the therapy of PTSD.", "The aim of this study was to investigate the potential use of mirtazapine in Korean veterans diagnosed with PTSD, by comparing it with sertraline, a drug approved for use in PTSD in the USA.\n Efficacy was evaluated by the clinician administered PTSD scale (CAPS-2), the Hamilton rating scale for depression (HAMD-17) and the clinical global impression scale (CGI), at baseline and at weeks 1, 2 and 6. A response was defined as a > or = 30 % decrease in CAPS-2 total severity, a > or = 50 % decrease in total HAMD-17 score, and a CGI-I score < 3.\n 51 patients on mirtazapine (mean age/duration of illness: 59.1/33.5 years) and 49 on sertraline (mean age/duration of illness: 60.6/35.6 years) completed the study. The mean daily dosage was 34.1 mg for mirtazapine and 101.5 mg for sertraline. On the CAPS-2 total score more patients responded in the mirtazapine group at week 1 (13 vs 2 %) and week 2 (51 vs 31 %). At week 6 this difference was statistically significant (88 % vs 69 %, p = 0.039) on the CAPS-2 total score. The HAMD-17 total score and CGI-I score decreased in both groups, with no significant differences between th groups on all time points. The main side effects for the mirtazapine group were: dry mouth (19.6 %), constipation (19.6 %), somnolence (15.7 %) and weight gain (1.96 %); and for the sertraline group: indigestion (14.3 %), palpitation (6.1 %), agitation (2.0 %), epigastric soreness (2.0 %), insomnia (2.0 %) and sexual dysfunction (2.0 %).\n Mirtazapine appeared to be an effective and well-tolerated treatment for PTSD in Korean veterans.\n 2004 John Wiley & Sons, Ltd.", "The anticonvulsant, lamotrigine, may be useful for symptom management in PTSD.\n Subjects enrolled in a 12-week double-blind evaluation of lamotrigine and placebo. Patients were randomized 2:1 to either lamotrigine or placebo. Lamotrigine was initiated at 25 mg/day and slowly titrated every 1 to 2 weeks over 8 weeks to a maximum dosage of 500 mg/day if tolerated.\n Fifteen subjects entered treatment, fourteen of whom returned for subsequent visits. Of 10 patients who received lamotrigine, 5 (50%) responded according to the DGRP, compared to 1 of 4 (25%) who received placebo. Lamotrigine patients showed improvement on reexperiencing and avoidance/numbing symptoms compared to placebo patients. Treatments were generally well tolerated.\n Lamotrigine may be effective as a primary psychopharmacologic treatment in both combat and civilian PTSD and could also be considered as an adjunct to antidepressant therapy used in the treatment of PTSD. These promising results warrant further large sample double-blind, placebo-controlled trials.", "Fluoxetine and placebo were studied in a population of combat veterans with severe, chronic PTSD.\n Twelve male veterans with PTSD were enrolled in a 12 week double-blind evaluation of fluoxetine and placebo. Mean fluoxetine dose at endpoint (week 12) was 48 mg/day with a range of 10 mg to 60 mg.\n One fluoxetine patient responded (17%) and two of the six placebo patients responded (33%).\n Fluoxetine patients did not show a greater response than placebo patients in this small sample of male combat veterans with severe, chronic PTSD. Fluoxetine has displayed an efficacious response in controlled studies of patients with PTSD who were predominantly female, suffered civilian (noncombat) traumas, and were overall experiencing less severe PTSD. The reasons for the low response rate to fluoxetine in our study is unknown and will await further study examining variables other than symptoms that might influence outcome, such as gender, comorbidity, prior treatment history, trauma type, severity and chronicity.", "Effects of double-blind treatment of chronic posttraumatic stress disorder (PTSD) with 2 SSRIs and placebo on emotional symptoms and autonomic reactivity were assessed prospectively. PTSD subjects received citalopram (n=25), sertraline (n=23), or placebo (n=10) for 10 weeks, with psychophysiologic assessments performed before and after treatment. Intent-to-treat analysis showed that all treatment groups improved significantly in total symptoms of PTSD (as measured by the Clinician Administered PTSD Scale), all 3 PTSD symptom clusters, and sleep time. However, subtle differences in improvements in PTSD symptom clusters, physiologic reactivity, and reported adverse events were identified. Citalopram treated subjects significantly lowered systolic and diastolic blood pressures, while sertraline and placebo treated patients significantly lowered only systolic blood pressure reactivity to individualized trauma scripts. The sertraline group showed significantly more improvement in avoidance/numbing symptoms than both other groups. Considering side effects, subjects on sertraline reported more gastrointestinal problems, with early terminators having more insomnia. Early terminators on citalopram reported more fatigue and appetite changes than other treatment groups, with completers reporting more sexual dysfunction. Results support a class effect of SSRIs in treating PTSD symptoms, but suggest a possible differential effect of drugs on symptom clusters, physiologic parameters, and side effects that may have clinical relevance. Implications of symptom reduction noted in the smaller placebo group are discussed relative to recent concerns about increasing placebo response in clinical trials.", "The objective of this double-blind, placebo-controlled study was to investigate the efficacy and safety of paroxetine in outpatients with posttraumatic stress disorder (PTSD).\n Male and female outpatients 18 years and older who met DSM-IV criteria for PTSD and had baseline scores of 50 or greater on the Clinician Administered PTSD Scale (CAPS-2) were randomly assigned to treatment with paroxetine (20-50 mg/day) or placebo for 12 weeks. The primary efficacy variables were the change from baseline to the 12-week endpoint in the CAPS-2 total score and the proportion of responders on the Clinical Global Impressions-Global Improvement scale (CGI-1). Additional key outcome measures were the change from baseline in the reexperiencing, avoidance/ numbing, and hyperarousal scores of the CAPS-2 and in the total scores of the Treatment Outcome PTSD Scale and the patient-rated Davidson Trauma Scale and Sheehan Disability Scale (SDS). Depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale. The proportion of patients achieving response and remission was also determined.\n 307 patients constituted the intent-to-treat population. At week 12, compared with the placebo group (N = 156), the paroxetine group (N = 151) showed significantly greater reduction of PTSD symptoms on both of the primary and all of the secondary outcome measures. Significantly greater improvement on the CAPS-2 total score was observed for paroxetine compared with placebo from week 4 (p < .05), and significantly greater proportions of paroxetine-treated patients achieved response (p < .001) and remission (p = .008) by week 12. The improvement in PTSD symptoms was similar in male and female patients. Functional improvement at the study endpoint was significantly greater (p < .05) in the paroxetine group in all 3 domains of the SDS (work, social life, family life). Treatment with paroxetine was well tolerated, with the frequency and type of adverse events recorded for the paroxetine group corresponding to the known safety profile of this medication. Conclusion: Paroxetine in doses of 20 to 50 mg once daily is effective as a treatment for chronic PTSD. Improvement is obtained for all 3 symptom clusters (reexperiencing, avoidance/numbing, hyperarousal) and is associated with significant reduction in disability after 12 weeks of treatment.", "Sixty male veterans with posttraumatic stress disorder (PTSD) participated in an 8-week, randomized trial comparing phenelzine (N = 19), imipramine (N = 23), and placebo (N = 18). Mean treatment retention was better on phenelzine (7.4 weeks) than on imipramine (5.6 weeks) or placebo (5.5 weeks). By week 5, both medications significantly reduced PTSD symptoms, as assessed by the Impact of Events Scale (IES), but the 44% improvement on phenelzine was greater than the 25% improvement on imipramine. The intrusion, but not the avoidance, subscale of the IES showed significant improvement, and the initial mild to moderate depressive symptoms did not significantly improve.", "Little is known about the effect of pharmacotherapy in the prevention of post-traumatic stress disorder (PTSD) relapse.\n To assess the efficacy and tolerability of fluoxetine in preventing PTSD relapse.\n This was a double-blind, randomised, placebo-controlled study. Following 12 weeks of acute treatment, patients who responded were rerandomised and continued in a 24-week relapse prevention phase with fluoxetine (n=69) or placebo (n=62). The primary efficacy assessment was the prevention of PTSD relapse, based on the time to relapse.\n Patients in the fluoxetine/fluoxetine group were less likely to relapse than patients in the fluoxetine/placebo group (P=0.027). There were no clinically significant differences in treatment-emergent adverse events between treatment groups.\n Fluoxetine is effective and well tolerated in the prevention of PTSD relapse for up to 6 months.", "Thirteen patients meeting DSM-III criteria for posttraumatic stress disorder participated in a random-assignment, double-blind crossover trial comparing phenelzine (45-75 mg/day) and placebo. Ten patients completed at least 4 weeks of each treatment phase. Clinical response to phenelzine did not differ from placebo, and overall improvement by the end of the study could not be attributed to the active drug. The findings are discussed in the light of preliminary reports suggesting that phenelzine may be an effective treatment for posttraumatic stress disorder." ]

[ "2965827", "12634941", "7790793", "4257208", "1105752", "6481516", "6451138", "6494835", "3011174", "6112444", "10457578", "11680522", "8211369", "8347073", "1535495" ]

[ "[Treatment of lumbar sciatica with or without neurological deficit using mechanical traction. A double-blind study].", "The efficacy of lumbar traction in the management of patients with low back pain.", "The efficacy of traction for lumbar back pain: design of a randomized clinical trial.", "Physical therapy on low back pain and sciatica. An attempt at evaluation.", "Lumbar traction: a double-blind controlled study for sciatica.", "Traction therapy in patients with herniated lumbar intervertebral discs.", "Auto-traction for treatment of lumbago-sciatica. A multicentre controlled investigation.", "Autotraction versus manual traction in patients with prolapsed lumbar intervertebral discs.", "A controlled trial of continuous lumbar traction in the treatment of back pain and sciatica.", "Multicentre trial of physiotherapy in the management of sciatic symptoms.", "Randomized trial comparing interferential therapy with motorized lumbar traction and massage in the management of low back pain in a primary care setting.", "A prospective randomized controlled study of VAX-D and TENS for the treatment of chronic low back pain.", "Comparison of sacrospinalis myoelectric activity and pain levels in patients undergoing static and intermittent lumbar traction.", "Autotraction versus passive traction: an open controlled study in lumbar disc herniation.", "Controlled trial of balneotherapy in treatment of low back pain." ]

[ "Traction therapy for low back pain with sciatica has been evaluated in a double blind study. 60 patients hospitalized for sciatica with or without signs of sensory or motor deficiency were randomized to 3 treatment groups: \"placebo traction\" (5 kg), \"light traction\" (15 kg) and \"normal traction\" (50 kg). Clinical evaluation after 4, 8 and 12 traction sessions showed no difference between the three groups.", "The literature on the efficacy of traction in the treatment of low back pain (LBP) is conflicting. The aim of this study was to examine its efficacy in this disorder. Forty-two patients with at least 6 weeks of nonspecific LBP were selected. Demographic data were obtained. All patients completed the Oswestry disability index (ODI) to assess disability and the 10-cm visual analog scale (VAS) for evaluation of pain. Subjects were randomly assigned into group 1, receiving only standard physical therapy, or group 2, receiving standard physical therapy with conventional lumbar traction. Standard physical therapy consisted of local heat, ultrasound for the lumbar region, and an active exercise program, given for ten sessions in all. The subjects received instruction on correct posture and recommended therapeutic exercises. They were reevaluated at the end of treatment and at 3-month follow-up. The mean outcome measures were global improvement and satisfaction with the therapy, as well as disability by ODI and pain by VAS. There were no group differences in terms of demographic and baseline clinical characteristics. There was a significant reduction in pain intensity and disability at the end of treatment in both groups. There was complete or mild improvement in 47.6% of group 1 and 40% of group 2. The satisfaction rate with both treatments was more than 70% immediately after the therapies. During the 3-month period, the outcome measures except disability remained statistically stable, with no difference amongst groups. Disability was significantly reduced at follow-up in both groups. Of the patients, 51% continued with the recommended exercises and had significantly lower disability scores than those who did not continue with the exercises. Pain and global improvement were also better in this group, but the difference was not statistically significant. In conclusion, no specific effect of traction on standard physical therapy was observed in our study group. We suggest focusing on back education and exercise therapy in the management of patients suffering from this chronic condition.", "To present the design of a trial on the efficacy of lumbar traction.\n Randomized clinical trial.\n Patients with a minimum of 6 wk, nonspecific low back pain.\n High-dose, motorized, continuous traction with a force between 35% and 50% of the total body weight was compared with sham or low-dose traction with a force between 0 and 20% of body weight. The sham traction was given with a specially developed brace that becomes tighter in the back during traction. This is experienced by patients as if traction were exerted.\n Primary measures were the patient's global impression of the effect and the severity of three main complaints. Secondary effect measures were functional status, pain, range of motion, work absence and recurrences. The effect measures were rated before randomization and 4 wk, 12 wk and 6 months later.\n There have been a number of earlier trials on the efficacy of lumbar traction; they suffer, however, from severe methodological flaws. This trial aimed to avoid these shortcomings.", "nan", "A double-blind control study of lumbar traction for sciatica has been carried out. Although there is a tendency for traction to produce improvement in pain and straight-leg raise the extent does not achieve statistical significance. Changing 'control' patients to 'treatment' seemed to produce worthwhile relief of pain for all who were not already improving. It is suggested that a large trial using more discriminating criteria might delineate a group of patients susceptible to help by traction.", "nan", "In this controlled prospective study of the Auto-traction method for the treatment of lumbago-sciatica, 82 patients were randomly allocated to either treatment with Auto-traction for up to three 1-hour sessions in 1 week, or they were given a corset and advised to rest. The orthopaedic surgeons participating in the study worked at six different hospitals and all had limited experience of the Auto-traction method obtained during a 1-week course. All patients were clinically evaluated by an independent observer who also performed the follow-up examinations 1 and 3 weeks after the treatment sessions. In addition a 3-month follow-up was performed by letter. The Auto-traction method gave prompt relief of pain and a normalizing of the SLR test more often than treatment with only a corset and rest. The difference between the two treatment groups was statistically significant. The immediate difference noted between the treatment groups had decreased slightly at 3 weeks but was still statistically significant at this time.", "Forty-nine patients with lumbago-sciatica and prolapsed lumbar intervertebral discs, comparable concerning anamnestical and clinical data were randomized for autotraction and manual traction given by the same therapist for a period of one week while strict bed rest was prescribed. A blind overall assessment performed immediately after the traction period, after two weeks follow-up training and three months after hospitalization showed that the two traction modalities are equally efficient. As treatment for hospitalized patients with lumbar intervertebral disc prolapses the relatively simple manual traction variety should be preferred, if any. Traction is suggested to be used as a prognostical aid. Pain intensity was significantly reduced in all body parts. About one fourth of patients avoided operation. After two years there was no recurrence of symptoms.", "A controlled trial of continuous lumbar traction in the treatment of back pain and sciatica showed similar improvements in both the treated group (weighted traction) and the control group (simulated traction). The findings of this study question the justification of admitting patients with back pain into hospitals for purposes of traction alone.", "Four treatments for sciatic symptoms--traction, exercises, manipulation, and corset--were assessed in a randomised controlled trial in 322 outpatients. The design was factorial. There were thus sixteen treatment groups, enabling a comparison of combinations of methods as well as of individual methods. Treatment lasted for four weeks. Patients were reviewed at the end of this period and at four and sixteen months after entry to the trial. Progress was measured by the patient's account of symptomatic improvement or deterioration and by return to work or normal activities. At four weeks each of the treatments was associated with a small degree of benefit over and above the high rate of spontaneous improvement. For manipulation, the benefit was statistically significant on one of the scales used to measure progress. There was a significant increase in symptomatic improvement with increasing numbers of treatments used in combination. This was complemented by a clear tendency for those who had received fewer types of treatment during the trial to have further treatment in the ensuing three months. There were no beneficial effects of treatment detectable at four or sixteen months. In the short-term, active physiotherapy with several treatments appears to be of value in the outpatient management of patients with sciatic symptoms, but it does not seem to confer any longer-term benefit.", "A randomized trial designed to compare interferential therapy with motorized lumbar traction and massage management for low back pain in a primary care setting.\n To measure and compare the outcome of interferential therapy and management by motorized lumbar traction and massage.\n Management of low back pain by interferential therapy and motorized lumbar traction and massage is common in Germany. No reports of previous randomized trials for the outcome from interferential therapy were found.\n Consenting patients were randomly assigned into one of two groups. A pretreatment interview was performed by the patient using a computer-based questionnaire. It also incorporated the Oswestry Disability Index and a pain visual analog scale. Management consisted of six sessions over a 2- to 3-week period. Oswestry Disability Indexes and pain visual analog scale scores also were obtained immediately after and at 3 months after treatment.\n A total of 152 patients were recruited. The two treatment groups had similar demographic and clinical baseline characteristics. The mean Oswestry Disability Index before treatment was 30 for both groups (n = 147). After treatment, this had dropped to 25, and, at 3 months, were 21 (interferential therapy) and 22 (motorized lumbar traction and massage). The mean pain visual analog scale score before treatment was 50 (interferential therapy) and 51 (motorized lumbar traction and massage). This had dropped, respectively, to 46 and 44 after treatment and to 42 and 39 at 3 months.\n This study shows a progressive fall in Oswestry Disability Index and pain visual analog scale scores in patients with low back pain treated with either-interferential therapy or motorized lumbar traction and massage. There was no difference in the improvement between the two groups at the end of treatment. Although there is evidence from several trials that traction alone is ineffective in the management of low back pain, this study could not exclude some effect from the concomitant massage.", "Low back pain is one of the most significant medical and socioeconomic problems in modern society. International guidelines call for evidence-based management for the pain and disability associated with musculoskeletal disorders. The purpose of this randomized controlled trial is to address the question of efficacy and appropriateness of vertebral axial decompression (VAX-D) therapy, a new technology that has been shown in clinical research to create negative intradiscal pressures, and has been shown to be effective in treating patients presenting with chronic low back pain (> 3 months duration) with associated leg pain. Successful outcome was defined as a 50% reduction in pain utilizing a 10 cm Visual Analog Pain Scale and an improvement in the level of functioning as measured by patient-nominated disability ratings. Patients were randomly assigned to VAX-D or to TENS which was used as a control treatment or placebo. The TENS treatment demonstrated a success rate of 0%, while VAX-D demonstrated a success rate of 68.4% (p < 0.001). A statistically significant reduction in pain and improvement in functional outcome was obtained in patients with chronic low back pain treated with VAX-D.", "The purposes of this study of low back pain patients were to determine: 1) if presence of sacrospinalis myoelectric activity is a consistent phenomenon in supine and prone positions; 2) if there is a difference between magnitudes of myoelectric activity for two types of lumbar traction (static and intermittent); and 3) if there is a difference in patient perceived pain level after traction between the two types of traction. Results show that surface electrode myoelectric activity is absent in resting supine and prone positions, there is no significant difference in magnitude of myoelectric activity between the two different types of traction, and more than 50% of patients in both traction groups experienced decreased pain after traction.", "Autotraction (AT) is a treatment for low-back pain syndrome of benign etiology that uses a specially designed traction table divided into two movable sections. While lying on the table, the pelvis secured, the patient controls the traction forces by grasping and pulling the bars at the head of the table. There are controls for the therapist to apply, through movable sections of the table, rotation and bending forces to help restore mobility to the lumbar spine without inducing pain. The present study is based upon a randomized treatment trial comparing conventional passive traction (PT) to AT. The following outcome indicators were used: (1) subjective response concerning overall improvement, (2) pain intensity (visual analog scale, 0-100), (3) qualitative pain severity (McGill Pain Questionnaire, short-form, 0-45), and (4) pain related disability (Oswestry Low Back Pain Disability Score, 0-100). The favorable response to AT was 75% (30 of the 40 patients) versus the 22% (6 of 27 patients) to PT (p < 0.001). After 3 months, 19 of the 30 responders to AT (63%) reported continued improvement. In these patients, pain ratings remained stable and the disability scores decreased to 0 to 23% of the pretreatment value (median and mean respectively, p < 0.001).", "Three treatments for non-specific lumbar pain--balneotherapy, underwater traction bath, and underwater massage--were assessed in a randomised prospective controlled trial in 158 outpatients. Each group was treated for four weeks and patients were reviewed at the end of this period and at 12 months after entry to the trial. The prescription of analgesics and the pain score were significantly reduced in all three treated groups, but there was no difference between the three groups. No significant change occurred in spinal motion and the straight leg raising test. After one year only the analgesic consumption was significantly lower than in the control group." ]

[ "11773176", "8158698", "8209274", "2159838" ]

[ "Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer.", "A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer.", "A randomized trial of mitomycin/ifosfamide/cisplatin preoperative chemotherapy plus surgery versus surgery alone in stage IIIA non-small cell lung cancer.", "Failure of the perioperative PCV neoadjuvant polychemotherapy in resectable bronchogenic non-small cell carcinoma. Results from a randomized phase II trial." ]

[ "To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC).\n A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy.\n Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033).\n Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.", "Patients with resectable stage IIIA non-small-cell lung cancer have a low survival rate following standard surgical treatment. Nonrandomized trials in which induction chemotherapy or a combination of chemotherapy and radiation prior to surgery were used to treat patients with regionally advanced primary cancers have suggested that survival is improved when compared with treatment by surgery alone.\n We performed a prospective, randomized study of patients with previously untreated, potentially resectable clinical stage IIIA non-small-cell lung cancer to compare the results of perioperative chemotherapy and surgery with those of surgery alone.\n This trial was designed to test the null hypothesis that the proportion of patients surviving 3 years is 12% for either treatment group against the alternate hypothesis that the 3-year survival rate would be 12% in the surgery alone group and 32% in the perioperative chemotherapy group. The estimated required sample size was 65 patients in each group. The trial was terminated at an early time according to the method of O'Brien and Fleming following a single unplanned interim analysis. The decision to terminate the trial was based on ethical considerations, the magnitude of the treatment effect, and the high degree of statistical significance attained. In total, 60 patients were randomly assigned between 1987 and 1993 to receive either six cycles of perioperative chemotherapy (cyclophosphamide, etoposide, and cisplatin) and surgery (28 patients) or surgery alone (32 patients). For patients in the former group, tumor measurements were made before each course of chemotherapy and the clinical tumor response was evaluated after three cycles of chemotherapy; they then underwent surgical resection. Patients who had documented tumor regression after preoperative chemotherapy received three additional cycles of chemotherapy after surgery.\n After three cycles of preoperative chemotherapy, the rate of clinical major response was 35%. Patients treated with perioperative chemotherapy and surgery had an estimated median survival of 64 months compared with 11 months for patients who had surgery alone (P < .008 by log-rank test; P < .018 by Wilcoxon test). The estimated 2- and 3-year survival rates were 60% and 56% for the perioperative chemotherapy patients and 25% and 15% for those who had surgery alone, respectively.\n In this trial, the treatment strategy using perioperative chemotherapy and surgery was more effective than surgery alone.\n This clinical trial strengthens the validity of using perioperative chemotherapy in the management of patients with resectable stage IIIA non-small-cell lung cancer. Further investigation of the perioperative chemotherapy strategy in earlier stage lung cancer is warranted.", "The efficacy of surgery or radiotherapy as conventional treatment for stage IIIA non-small cell lung cancer (NSCLC) is limited. Recent studies have pointed out that preoperative chemotherapy may improve survival. To reconcile the two approaches, we undertook a multidisciplinary randomized trial to examine the possible synergism between preoperative chemotherapy and surgery in improved survival. Stage IIIA NSCLC patients were randomly assigned to receive either three preoperative courses of mitomycin/ifosfamide/cisplatin chemotherapy and surgery or surgery alone. The median survival was significantly greater in the chemotherapy plus surgery group than in the surgery group (26 months v 8 months; P < .001). However, the prognostic value of the mutated K-ras gene data presented awaits the analysis of larger sample populations. Similarly, the role of high-dose cisplatin in inducing higher pathologic complete remissions has to be corroborated in future randomized trials.", "In 1985, the authors began a phase II study to assess the PCV perioperative polychemotherapy (cisplatin 100 mg/m2, cyclophosphamide 600 mg/m2, vindesine 3 mg/m2) in patients with resectable bronchogenic non-small cell carcinoma. Patients were randomized to receive either two preoperative courses of PCV chemotherapy, surgery, and two postoperative courses of PCV chemotherapy (PCV group) or immediate surgery (surgery group). A staging procedure using the CT scan was performed before randomization and, additionally, before surgery in the PCV group. There were 26 randomized patients, 13 in each group. In the PCV group, 11 patients agreed to receive the two preoperative courses of chemotherapy. A response was observed in five patients (45%), and a progression was observed in four patients (36%) leading to a cancellation of surgery in two of them. Postoperative care was the same for each group. Although no death could be related to chemotherapy, it was decided to stop entering new patients into this trial because of the rate of preoperative progression in the PCV group." ]

[ "16585301", "19866403" ]

[ "Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study.", "The use of sildenafil in persistent pulmonary hypertension of the newborn." ]

[ "Persistent pulmonary hypertension (PPHN) occurs in as many as 6.8 of 1000 live births. Mortality is approximately 10% to 20% with high-frequency ventilation, surfactant, inhaled nitric oxide, and extracorporeal membrane oxygenation but is much higher when these therapies are not available. Sildenafil is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance.\n Our goal was to evaluate the feasibility of using oral sildenafil and its effect on oxygenation in PPHN.\n This study was a proof-of-concept, randomized, masked study in infants >35.5 weeks' gestation and <3 days old with severe PPHN and oxygenation index (OI) >25 admitted to the NICU (Hospital Niño Jesús, Barranquilla, Colombia). The sildenafil solution was prepared from a 50-mg tablet. The first dose (1 mg/kg) or placebo was given by orogastric tube <30 minutes after randomization and every 6 hours. Preductal saturation and blood pressure were monitored continuously. OI was calculated every 6 hours. The main outcome variable was the effect of oral sildenafil on oxygenation. Sildenafil or placebo was discontinued when OI was <20 or if there was no significant change in OI after 36 hours.\n Six infants with an OI of >25 received placebo, and 7 received oral sildenafil at a median age of 25 hours. All infants were severely ill, on fraction of inspired oxygen 1.0, and with similar ventilatory parameters. Intragastric sildenafil and placebo were well tolerated. In the treatment group, OI improved in all infants within 6 to 30 hours, all showed a steady improvement in pulse oxygen saturation over time, and none had noticeable effect on blood pressure; 6 of 7 survived. In the placebo group, 1 of 6 infants survived.\n Oral sildenafil was administered easily and tolerated as well as placebo and improved OI in infants with severe PPHN, which suggests that oral sildenafil may be effective in the treatment of PPHN and underscores the need for a large, controlled trial.", "We evaluated the effectiveness of sildenafil in the treatment of neonatal pulmonary hypertension. We performed a double-blind randomized clinical trial in 51 full-term infants with persistent pulmonary hypertension confirmed by Doppler echocardiography. Patients were divided in two groups: 20 infants in group A received placebo when the oxygenation index was >20, and 31 infants in group B received 3 mg/kg of oral sildenafil every 6 hours. Arterial blood gases were taken at 1, 4, 7, 13, 19, and 25 hours after treatment was started. Main outcome measures were oxygenation changes, time on mechanical ventilation, and mortality. Both groups were comparable in general variables as well as in illness severity. We observed better oxygenation parameters after 7 hours of sildenafil treatment, but no significant changes were found in the placebo group. Mortality was higher in the placebo group (40%) than in those infants who received sildenafil (6%; P = 0.004), although no difference was found in time on mechanical ventilation between groups. Our results confirm that sildenafil may be a useful adjuvant therapy for term infants with pulmonary hypertension in centers lacking inhaled nitric oxide and extracorporeal membrane oxygenation.\n Thieme Medical Publishers." ]

[ "9841585", "9570235", "10574137", "8225695" ]

[ "Oral thymic extract for chronic hepatitis C in patients previously treated with interferon. A randomized, double-blind, placebo-controlled trial.", "Preliminary report of a randomized, double-blind placebo-controlled trial of a Chinese herbal medicine preparation CH-100 in the treatment of chronic hepatitis C.", "Intravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trial.", "A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis." ]

[ "Hepatitis C is an important cause of chronic liver disease. It is claimed that Complete Thymic Formula, an over-the-counter herbal dietary supplement, is beneficial for patients with hepatitis C.\n To evaluate the efficacy and safety of Complete Thymic Formula.\n Randomized, double-blind, placebo-controlled trial.\n Tertiary referral center.\n 38 patients with hepatitis C who did not respond to or were intolerant of interferon therapy.\n Complete Thymic Formula for 3 to 6 months or placebo for 3 months.\n Serial measurements of hepatitis C virus (HCV) RNA titers.\n No differences were noted at 3 months between the placebo group (n = 13) and the treatment group (n = 19) in mean HCV RNA titers (4.06 +/- 1.52 x 10(6) copies/mL compared with 3.48 +/- 1.92 x 10(6) copies/mL; P > 0.2). The 19 patients who completed 6 months of treatment with Complete Thymic Formula remained positive for HCV, and their mean HCV RNA titers were similar at 6 months and at baseline (2.78 +/- 1.96 x 10(6) copies/mL compared with 3.12 +/- 1.94 x 10(6) copies/mL; P > 0.2).\n Complete Thymic Formula did not benefit patients who had previously received interferon therapy. Patients should be advised about use of this over-the-counter compound.", "The treatment of chronic hepatitis C is relatively unsatisfactory and many patients have turned to unproven alternative medicines to modify the course of their illness. We report a study of a Chinese herbal medicine preparation CH-100 in the management of chronic hepatitis C. Patients with documented chronic hepatitis C were randomly allocated to receive active herbal or placebo tablets (five tablets thrice daily). Patients were followed monthly and evaluated by a Western and a traditional Chinese medical practitioner. Therapy was monitored by measurement of liver function tests, creatinine and full blood count on a monthly basis. Twenty patients in each group were well matched for age, sex, duration of illness, previous interferon therapy and alcohol intake. Active Chinese herbal medication was associated with a significant reduction in alanine aminotransferase (ALT) levels over the 6 month study period (P < 0.03). No patient cleared the virus but four normalized their ALT on treatment. Appropriately prescribed Chinese herbal medicine may have a role in the management of chronic hepatitis C and further controlled studies are indicated.", "In Japan, glycyrrhizin therapy is widely used for chronic hepatitis C and reportedly reduces the progression of liver disease to hepatocellular carcinoma. The aims of this study were to evaluate the effect of glycyrrhizin on serum alanine aminotransferase (ALT), hepatitis C virus (HCV)-RNA and its safety in European patients.\n Fifty-seven patients with chronic hepatitis C, non-responders or unlikely to respond (genotype 1/cirrhosis) to interferon therapy, were randomized to one of the four dose groups: 240, 160 or 80 mg glycyrrhizin or placebo (0 mg glycyrrhizin). Medication was administered intravenously thrice weekly for 4 weeks; follow up also lasted for 4 weeks.\n Within 2 days of start of therapy, serum ALT had dropped 15% below baseline in the three dosage groups (P < 0.02). The mean ALT decrease at the end of active treatment was 26%, significantly higher than the placebo group (6%). A clear dose-response effect was not observed (29, 26, 23% ALT decrease for 240, 160 and 80 mg, respectively). Normalization of ALT at the end of treatment occurred in 10% (four of 41). The effect on ALT disappeared after cessation of therapy. During treatment, viral clearance was not observed: the mean decrease in plasma HCV-RNA after active treatment was 4.1 x 10(6) genome equivalents/mL (95% confidence interval, 0-8.2 x 10(6); P > 0.1). No major side-effects were noted. None of the patients withdrew from the study because of intolerance.\n Glycyrrhizin up to 240 mg, thrice weekly, lowers serum ALT during treatment, but has no effect on HCV-RNA levels. The drug appears to be safe and is well tolerated. In view of the reported long-term effect of glycyrrhizin, further controlled investigation of the Japanese mode of administration (six times weekly) for induction appears of interest.", "In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (+/- SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase (ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/- 4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to 0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH." ]

[ "8988693", "21585643" ]

[ "Stepwise compared with rapid application of vacuum in ventouse extraction procedures.", "Rapid versus stepwise application of negative pressure in vacuum extraction-assisted vaginal delivery: a multicentre randomised controlled non-inferiority trial." ]

[ "To compare a one-step (rapid) application of negative pressure (vacuum) with conventional stepwise application for ventouse extraction following a prolonged second stage of labour.\n Randomised controlled study.\n Teaching Hospital.\n Forty-seven women were randomised to the rapid vacuum group and 47 to the stepwise group.\n Duration of ventouse procedure, effectiveness of methods of application, morbidity of mother and infant.\n There was no significant difference in frequency of detachment of the cup after rapid or stepwise application of vacuum. A reduction in mean duration of the ventouse procedure of 6 min was realised without significant difference in maternal or neonatal morbidity.\n Rapid application of vacuum significantly reduces the duration of a ventouse extraction procedure without compromise to efficiency and safety.", "To evaluate whether the application of rapid negative pressure for vacuum-assisted delivery is as effective and safe as the stepwise method.\n Randomised controlled trial.\n Six centres, including university, secondary and tertiary hospitals, in Thailand.\n In total, 662 women were randomised to rapid and stepwise groups, with 331 women in each group.\n Vacuum extraction was performed by applying a metal cup (Malmstrom) connected to an electric pump to the fetal head. The stepwise method consisted of four incremental steps of 0.2 kg/cm² every 2 minutes to obtain a final negative pressure of 0.8 kg/cm². In the rapid method the negative pressure of 0.8 kg/cm² was applied in one step in < 2 minutes.\n Success rate of vacuum extraction, vacuum cup detachment rate, duration of vacuum extraction, and maternal and neonatal complications.\n There were no significant differences in detachment rates (RD 0.3%, 95% CI -3.1 to 2.4). The overall success rates were identical, at 98.2%. There were significant reductions in the time between applying the vacuum cup and attaining maximum negative pressure (MD -4.6 minutes; 95% CI -4.4 to -4.8 minutes), and in the time between applying the cup and delivery (MD -4.4 minutes; 95% CI -4.8 to -4.0 minutes). There was a significantly higher rate of perineal suture in the rapid method group (RD 4.5%; 95% CI 1.1-8.2). There were no significant differences in maternal and fetal morbidities.\n Rapid negative pressure vacuum extraction could be performed as effectively and safely as the stepwise method, in a shorter period of time.\n © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG." ]

[ "8613046" ]

[ "Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial." ]

[ "Uncontrolled studies have suggested that methotrexate may be effective in patients with active ulcerative colitis. The aim of this study was to evaluate the effectiveness of oral methotrexate in chronic steroid-dependent ulcerative colitis in a randomized, double-blind multicenter trial.\n Patients with active ulcerative colitis who have received steroids and/or immunosuppressives for at least 4 months during the preceding 12 months with a current Mayo Clinic score of > or = 7 were included in the study. Methotrexate (12.5 mg) or placebo was added to their treatment once weekly for 9 months.\n Sixty-seven patients were included (methotrexate, 30 patients, placebo, 37 patients). The proportion of patients entering first remission (methotrexate, 46.7%; placebo, 48.6%), the time to reach first remission (methotrexate, 4.1 +/- 1.9 months; placebo, 3.4 +/- 1.7 months), as well as the proportions of patients having a relapse after first remission (methotrexate, 64.3%; placebo, 44.4%) were not significantly different between the two groups. The mean Mayo Clinic score, the mean monthly steroid dose, and the proportion of abnormal laboratory results during the study were also similar.\n Methotrexate at a weekly oral dose of 12.5 mg was not found to be better than placebo in the induction or maintenance of remission in patients with chronic active ulcerative colitis." ]