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[ "7079035", "2740166", "6723452", "8518642" ]

[ "Effects of parent training on teenage mother and their infants.", "Home visiting of varying frequency and child development.", "Home again: effects of the Mother-Child Home Program on mother and child.", "Community mothers' programme: randomised controlled trial of non-professional intervention in parenting." ]

[ "Parent training was provided for 80 low-income, black teenage mothers during their infants' first six months. Half of the mothers were visited biweekly in their homes to be instructed in caregiving and in sensorimotor and interaction exercises, and half were trained as CETA (Comprehensive Employment Training ACT)-paid, teacher's aides in a medical school infant nursery that provided care for their infants and infants of medical faculty. Growth and development during the first two years were superior for the infants whose mothers received training, particularly those who received paid parent training as teacher's aides in the infant nursery. Repeat pregnancy rates were lower and return to work/school rates were higher for the infant nursery mothers, most of whom subsequently pursued nurse's aide training.", "Two studies were made of home visiting and psychosocial stimulation with deprived urban children in Jamaica. The aim was to determine the relative effectiveness of different frequencies of visiting on the children's developmental levels and the feasibility of integrating the model into government primary health care services. Health paraprofessionals supervised by a nurse from a local health center conducted the intervention. In the first study, 152 children aged 6 to 30 months were assigned to groups visited biweekly, monthly, or not at all by area of residence. The biweekly group showed small but significant increases in scores on the Griffiths Mental Development Scales (developmental quotient) and performance subscale compared with the monthly and control groups, whereas no benefit was shown in the Griffiths scores of the monthly group. In the second study, 58 children aged 16 to 30 months from the same neighborhoods were randomly assigned to weekly visited and control groups. The group visited weekly showed marked improvements in the performance and hearing and speech subscales as well as the developmental quotient scores. The results indicate that as the frequency of visiting increases from none through monthly and biweekly to weekly, the benefits increase as well.", "4 successive cohorts of low-income families were randomly assigned either to a home-based intervention program that focused on modeling verbal interaction between mother and child around selected toys and books or to comparison treatments. Large program effects were found on maternal interaction styles in videotaped observations. Small IQ and program-specific effects were found for children in contrast to much larger IQ effects found in earlier research. IQ effects did not appear to have been mediated by changes in maternal behavior. A variation in which toys and books were supplied without home visits was as effective as the full program on IQ but not on maternal behavior. 3 years postprogram , there were no detectable effects in achievement or IQ tests or in first grade teachers' ratings of school adjustment and performance, but IQ and achievement scores were near national norms. Reasons for discrepancies with earlier results are discussed. The results highlight the need for continued experimental evaluation of early intervention programs with safeguards to insure that samples are educationally at risk.", "To see whether non-professional volunteer community mothers could deliver a child development programme to disadvantaged first time mothers for children aged up to 1 year.\n Randomised controlled trial.\n A regional health authority in Dublin.\n 262 first time mothers who were delivered during six months in 1989 and who lived in a deprived area of Dublin; 30 experienced mothers from the same community recruited as community mothers.\n All the first time mothers received standard support from the public health nurse. In addition, those in the intervention group received the services of a community mother, who was scheduled to visit monthly during the first year of the child's life.\n 232 (89%) first time mothers completed the study--127 in the intervention group, 105 controls. At the end of the study children in the intervention group were more likely to have received all of their primary immunisations, to be read to, and to be read to daily, played more cognitive games; and were exposed to more nursery rhymes. They were less likely to begin cows' milk before 26 weeks and to receive an inappropriate energy intake and inappropriate amounts of animal protein, non-animal protein, wholefoods, vegetables, fruit, and milk. Mothers in the intervention group also had a better diet than controls. At the end of the study they were less likely to be tired, feel miserable, and want to stay indoors; had more positive feelings; and were less likely to display negative feelings.\n Non-professionals can deliver a health promotion programme on child development effectively. Whether they can do so as effectively as professionals requires further study." ]

[ "15358979", "16818861", "11481167", "15667429", "7509495", "15863811", "16754835", "11041534", "14624201", "9989566", "17651705", "9131723", "9545995", "11823268", "12755665", "11163780" ]

[ "Cerebral D2 and 5-HT2 receptor occupancy in Schizophrenic patients treated with olanzapine or clozapine.", "Childhood-onset schizophrenia: A double-blind, randomized clozapine-olanzapine comparison.", "A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia.", "Randomized double blind comparison of olanzapine vs. clozapine on subjective well-being and clinical outcome in patients with schizophrenia.", "Risperidone versus clozapine in the treatment of schizophrenic patients with acute symptoms: a double blind, randomized trial.", "The effects of clozapine and risperidone on spatial working memory in schizophrenia.", "Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder.", "Risperidone versus clozapine in treatment-resistant schizophrenia: a randomized pilot study.", "The efficacy of high-dose olanzapine versus clozapine in treatment-resistant schizophrenia: a double-blind crossover study.", "Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response.", "Clozapine and \"high-dose\" olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison.", "Improvement of cognitive function in schizophrenic patients receiving clozapine or zotepine: results from a double-blind study.", "Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. The Risperidone Study Group.", "Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder.", "Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics.", "Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine." ]

[ "We report the results of a double-blind, randomized prospective trial on D2 and 5-HT2 receptor occupancy and the clinical effects of olanzapine versus clozapine in a sample of neuroleptic-refractory schizophrenic patients. Receptor occupancy was evaluated in different cortical areas and in basal ganglia using [18F] fluoro-ethyl-spiperone ([18F] FESP) and positron emission tomography (PET). A total of 15 neuroleptic-free patients completed the study undergoing a baseline and a post-treatment PET scan (olanzapine, nine patients, one female; clozapine, six patients, three female) 8 weeks after starting treatment. PET data were analysed both by regions of interest and on a voxel-by-voxel basis using Statistical Parametric Mapping (SPM96). Olanzapine and clozapine induced a similar and significant inhibition of [18F] FESP binding index in the cortex. In the basal ganglia, receptor occupancy was significantly higher with olanzapine than with clozapine (p=0.0018). By contrast, no differences in receptor occupancy were detected at the level of the pituitary gland. Clinical outcomes, in particular a full extra pyramidal tolerability, were similar. In this sample of neuroleptic-refractory schizophrenic patients, olanzapine and clozapine showed a different pattern of occupancy of D2-like receptor despite a common lack of extrapyramidal side-effects.", "Childhood-onset schizophrenia is a rare but severe form of the disorder that is frequently treatment resistant. The psychiatrist has a limited evidence base to guide treatment, particularly as there are no trials in children comparing atypical antipsychotics, the mainstay of current treatment.\n To compare the efficacy and safety of olanzapine and clozapine, hypothesizing that clozapine would be more efficacious.\n Double-blind randomized 8-week controlled trial, with a 2-year open-label follow-up.\n National Institute of Mental Health study, January 1998 to June 2005. Patients underwent reassessment 2 years after discharge.\n Children and adolescents recruited nationally, aged 7 to 16 years, meeting unmodified DSM-IV criteria for schizophrenia, and resistant to treatment with at least 2 antipsychotics.\n After drug washout and a 1- to 3-week antipsychotic-free period, patients were randomized to treatment with clozapine (n = 12) or olanzapine (n = 13).\n The Clinical Global Impression Severity of Symptoms Scale and Schedule for the Assessment of Negative/Positive Symptoms.\n Clozapine was associated with a significant reduction in all outcome measures, whereas olanzapine showed a less consistent profile of clinical improvement. While there were moderate to large differential treatment effects in favor of clozapine, these reached significance only in the alleviation of negative symptoms from an antipsychotic-free baseline (P = .04; effect size, 0.89). Clozapine was associated with more overall adverse events. At 2-year follow-up, 15 patients were receiving clozapine with evidence of sustained clinical improvement, but additional adverse events emerged, including lipid anomalies (n = 6) and seizures (n = 1).\n While not demonstrating definitively the superiority of clozapine compared with olanzapine in treatment-refractory childhood-onset schizophrenia, the study suggests that clozapine has a more favorable profile of clinical response, which is balanced against more associated adverse events.", "This prospective, double-blind, multicenter, parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response.\n Male or female patients aged 18-65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response (N=273) were randomly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments. The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. Adverse events were recorded throughout the study.\n The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group. Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures (Positive and Negative Syndrome Scale, Calgary Depression Scale, Psychotic Depression Scale, and Psychotic Anxiety Scale). The adverse event profile was similar for both treatment groups, with a lower risk of extrapyramidal symptoms in the clozapine group.\n Clozapine showed superior efficacy over risperidone in this patient population. Both treatments were equally well tolerated as demonstrated through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone.", "This randomized double-blind multicenter trial evaluated the effects of olanzapine vs. clozapine on subjective well-being, quality of life (QOL) and clinical outcome.\n The primary objective was to demonstrate non-inferiority of olanzapine, mean dosage 16.2 +/- 4.8 (5-25 mg/day) vs. clozapine, mean dosage 209 +/- 91 (100-400 mg/day) regarding improvement on the 'Subjective Well-Being under Neuroleptic Treatment' (SWN) Scale after 26 treatment weeks in 114 patients with schizophrenia. Secondary outcome parameters included: Munich QOL Dimension List (MLDL), Positive and Negative Symptom Scale (PANSS), Clinical Global Impression (CGI).\n SWN scores improved significantly in both groups, olanzapine was non-inferior to clozapine (group difference 3.2 points in favor of olanzapine; 95% CI: 4.2;10.5). MLDL-satisfaction, PANSS and CGI-S improved similarly, olanzapine yielded a higher CGI Therapeutic Index. Individual SWN and PANSS changes correlated only moderately (r = -0.45).\n Olanzapine was non-inferior to clozapine. The lack of a marked correlation between PANSS and SWN improvements indicates that patients and psychiatrists perceive treatment differently.", "1. In order to verify the hypothesis that risperidone is a useful therapeutic alternative to clozapine the authors carried out a randomized double blind trial in 59 patients with paranoid hallucinatory psychoses. 2. In a treatment lasting 28 days three groups of patients received either 4 mg risperidone (N = 20), 8 mg risperidone (N = 19), or 400 mg clozapine (N = 20) daily. 3. The tolerance of 4 mg risperidone was globally assessed as being better than that of 400 mg clozapine. Drop-outs under clozapine were mostly caused by side effects, whereas under risperidone they tended to occur for therapeutic inefficacy. 4. The antipsychotic effect was highly significant and clinically relevant under both risperidone and clozapine.", "The purpose of this investigation was to evaluate the effects of clozapine and risperidone on spatial working memory in patients with schizophrenia.\n Spatial working memory performance was evaluated at baseline and after 17 and 29 weeks in 97 patients with schizophrenia participating in a multisite trial.\n Compared with baseline performance while receiving conventional antipsychotic medication, risperidone improved, and clozapine worsened, spatial working memory performance.\n The differential effects of these medications on spatial working memory may be due to the anticholinergic effects of clozapine and prefrontal dopamine-enhancing effects of risperidone.", "Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance.\n To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.\n Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36).\n Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS).\n Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales.\n Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.", "1. The atypical antipsychotic risperidone may constitute an alternative to clozapine, the current treatment of choice for refractory schizophrenia. The objectives of this study were to evaluate the effectiveness of risperidone in comparison to clozapine in everyday practice and to assess the feasibility of a pragmatic trial procedure. 2. Patients were randomly assigned to open-label clozapine or risperidone treatment for 10 weeks and treatment outcomes were assessed blindly. Twenty-one patients were recruited and nineteen entered the randomized phase. 3. Five of 10 participants allocated to clozapine and one of nine risperidone participants dropped out before study completion. Five clozapine patients and six risperidone patients achieved clinical improvement, defined as a 20% decrease in the Positive and Negative Symptom Scale (PANSS) total score. No significant differences between the groups were detected in baseline or endpoint positive or negative symptoms, disease severity, or global or social functioning scores. Patients' opinion on the drugs did not differ between groups. 4. The findings of the intention-to-treat analysis of this study corroborates previous findings that risperidone may be equally effective as clozapine, and supports the feasibility and need of a multicenter randomized pragmatic trial with sufficient power to detect differences between treatments.", "nan", "Clozapine and risperidone were the first two \"second-generation\" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents.\n After a baseline fluphenazine treatment period, 29 patients participated in a 6-week, double-blind, parallel-group comparison of the effects of these agents.\n Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone.\n The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed.", "The present study evaluated the effectiveness and safety of clozapine versus \"high-dose\" olanzapine in treatment-refractory adolescents with schizophrenia.\n Children, ages 10-18 years, who met DSM-IV criteria for schizophrenia and who were resistant or intolerant to at least two antipsychotic drugs were randomized to receive 12 weeks of double-blind flexibly dosed treatment with clozapine (n = 18) or \"high-dose\" olanzapine (up to 30 mg/day) (n = 21). The primary efficacy measure was response (improvement), defined as a decrease of 30% or more in total Brief Psychiatric Rating Scale score from baseline and a Clinical Global Impression Scale improvement rating of \"1\" (very much improved) or \"2\" (much improved).\n Significantly more clozapine-treated adolescents met response criteria (66%) compared with olanzapine-treated subjects (33%). Clozapine was superior to olanzapine in terms of reduction of the psychosis cluster scores and negative symptoms from baseline to end point. However, both treatments were associated with significant weight-gain and related metabolic abnormalities.\n This double-blind randomized comparison of two second-generation antipsychotic drugs for treatment-refractory adolescents with schizophrenia supports clozapine as the agent of choice. The development of interventions to limit weight gain and metabolic side effects are needed to enhance the risk-benefit profile for both study treatments.", "Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia and the cognitive dysfunction associated with the disease. While clozapine has been shown to be effective in this respect, no data are available on zotepine. We report on a double-blind randomized study designed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia. Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity. Passage time, route, and motor errors were evaluated. 25 schizophrenic (DSM-IIIR) patients were included in each group. After washout, they were randomized on zotepine or clozapine and given up to 450 mg of substance each. Patients were followed for six weeks and evaluated weekly. We report on a subsample of 26 patients matched for baseline BPRS, SANS, and age. 13 matched healthy persons were recruited as controls. ANOVA with group and course over time as factors was used for analysis. Both clozapine and zotepine achieved a highly significant decrease in overall symptoms (BPRS) and negative symptoms (SANS). Zotepine and clozapine were equally effective. In the maze tests, motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a \"trait\" marker. In passage time and maze route, schizophrenics performed worse than controls. An improvement by medication was evident in both medication groups, but was more pronounced in the zotepine-treated group. The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia. The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction, confirming this substance's value as an atypical antipsychotic.", "The purpose of this study was to compare the short-term efficacy and safety of risperidone and clozapine in treatment-resistant chronic schizophrenic patients.\n In a controlled double-blind, multicenter study, 86 inpatients with chronic schizophrenia (DSM-III-R), who were resistant to or intolerant of conventional neuroleptics, were randomly assigned to receive risperidone or clozapine for 8 weeks after a 7-day washout period. After a 1-week dose-titration phase, doses were fixed at 6 mg/day of risperidone and 300 mg/day of clozapine for 1 week and then adjusted according to each patient's response. The final mean doses were 6.4 mg/day of risperidone and 291.2 mg/day of clozapine. Treatment efficacy and safety were evaluated with several well-known rating scales.\n Both risperidone and clozapine significantly reduced the severity of psychotic symptoms (scores on the Positive and Negative Syndrome Scale and the Clinical Global Impression scale) from baseline, with no significant between-group differences. At endpoint, 67% of the risperidone group and 65% of the clozapine group were clinically improved (reduction of 20% or more in total Positive and Negative Syndrome Scale score). Risperidone appeared to have a faster onset of action. In both groups extrapyramidal symptoms and other adverse events were few, and their severity was generally mild. Neither group showed evidence of a relation between drug plasma concentrations and clinical effectiveness.\n Risperidone was well tolerated and as effective as medium doses of clozapine in patients with chronic schizophrenia who had been resistant to or intolerant of conventional neuroleptics.", "The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder.\n In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period).\n Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain.\n The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.", "Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain.\n The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002.\n Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups.\n Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine.", "The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge. Clozapine has been one treatment option; however, it is not universally effective and is limited in its use by safety concerns. With the introduction of newer agents, their performance relative to clozapine is of great clinical interest.\n The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients. The study was primarily designed to demonstrate the \"noninferiority\" of olanzapine compared to clozapine after 18 weeks of double-blind treatment. Conclusions were based on the one-sided lower 95% confidence limit about the treatment effect observed from the primary efficacy variable (Positive and Negative Syndrome Scale [PANSS] Total).\n Mean changes from baseline to end point in PANSS Total score, using a last observation carried forward technique, showed that both agents were comparably effective in neuroleptic resistant patients, i.e., demonstrated the \"noninferiority\" of olanzapine when compared to clozapine. Overall, significantly fewer olanzapine-treated patients (4%) discontinued for an adverse event than their clozapine-treated (14%) counterparts (p =.022). Among spontaneously reported adverse events, increased salivation, constipation, dizziness, and nausea were reported significantly more often among clozapine-treated patients, whereas only dry mouth was reported more often among olanzapine-treated patients.\n Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinically eligible for treatment with clozapine." ]

[ "380773", "366350", "347992" ]

[ "Flunisolide nasal spray for perennial rhinitis in children.", "Beclomethasone dipropionate aerosol in the treatment of children with severe perennial rhinitis.", "Beclomethasone dipropionate in pediatric perennial extrinsic rhinitis." ]

[ "Twenty-seven children with perennial rhinitis entered a double-blind cross-over study comparing nasal sprays of flunisolide---a new topical corticosteroid---and placebo. Symptoms were assessed over two consecutive monthly periods with each treatment. Weekly diary cards, monthly clinical assessments, and end-of-trial preferences all favoured the active drug. At the end of the trial 20 patients preferred the treatment month with flunisolide, four preferred the placebo month, and two rated the periods equally. Side effects were mild, the commonest being transient nasal stinging. Seventeen children who derived benefit from flunisolide continued with the treatment for a six-month open-study period. Many reduced the dosage from three times to twice or once daily without losing benefit. The effect of flunisolide on the pituitary-adrenal axis was assessed in seven children by measuring the 0900 blood cortisol concentrations at two-month intervals over the six months. No effect was observed. The results show that flunisolide is effective and safe for the treatment and prophylaxis of perennial rhinitis in children.", "Twenty-two children suffering from severe perennial rhinitis were treated with intranasal beclomethasone dipropionate (300 microgram/day) and an identical placebo aerosol in a double-blind cross-over trial. The results confirmed the value of beclomethasone dipropionate in improving nasal symptoms and signs due to perennial rhinitis, and allergic eye symptoms caused by associated conjunctivitis.", "A double-blind, crossover trial of beclomethasone dipropionate intranasal aerosol was undertaken in 30 children suffering from long-term perennial extrinsic rhinitis refractive to conventional therapy with a success rate of 83%. There were no side effects. Maximum improvement was a seen a week after initiation of the active drug. Nasal blockage and rhinorrhoea were most responsive. It is suggested the beclomethasone dipropionate is an effective and safe treatment of children suffering from extrinsic perennial rhinitis." ]

[ "2926574", "3897499", "2407200" ]

[ "Posthemorrhagic hydrocephalus in high-risk preterm infants: natural history, management, and long-term outcome.", "Serial lumbar punctures in prevention of post-hemorrhagic hydrocephalus in preterm infants.", "Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation. Ventriculomegaly Trial Group." ]

[ "The natural history, medical management, and outcome in infants with progressive posthemorrhagic hydrocephalus after intraventricular hemorrhage were studied prospectively. Infants with asymptomatic severe posthemorrhagic hydrocephalus were managed with a predetermined protocol. Outcome between groups at 1 to 2 years and at more than 3 years was compared. The natural history study, restricted to the inborn population, revealed that posthemorrhagic hydrocephalus developed in 53 of 409 infants with intraventricular hemorrhage. The progression of hydrocephalus either was arrested or regressed in 35 of 53 infants; progression to severe hydrocephalus occurred in 18 of 53 infants. The severe posthemorrhagic hydrocephalus was asymptomatic in 16 of 18 infants. The management and outcome study included both inborn and outborn infants. Of 50 infants, 12 had symptomatic severe hydrocephalus and 38 had asymptomatic severe hydrocephalus. The 16 infants managed with close observation were as likely to remain shunt free as the 22 infants managed with serial lumbar punctures. Of 38 infants, 20 were managed without shunts. At 3 to 6 years, the outcome of infants in the close observation group did not differ from that in the lumbar puncture group. Long-term outcome of infants with progression to asymptomatic severe hydrocephalus did not differ from that of infants in whom disease progression was arrested. Poor outcome in infants with intraventricular hemorrhage and subsequent posthemorrhagic hydrocephalus was related to severity of hemorrhage and gestational age at birth less than 30 weeks. Because long-term outcome of infants with severe hydrocephalus did not differ from that of infants in whom the progression of hydrocephalus was arrested or whose condition improved before hydrocephalus became severe, we currently attempt medical management of these infants.", "We studied 47 infants with either grade 3 or grade 4 intraventricular hemorrhage, to assess the efficacy of intermittent lumbar punctures in the prevention of post-hemorrhagic hydrocephalus in a prospective controlled trial. The control group received supportive care only, whereas the treatment group additionally underwent intermittent spinal taps. The spinal taps were started at postnatal age 11 +/- 5 days and continued for 20 +/- 16 days, with the removal of 67 +/- 101 ml cerebrospinal fluid using 16 +/- 12 taps. The two groups were comparable with regard to birth weight, gestational age, race, sex, Apgar score, and severity of hemorrhage. Three infants in the control group died, compared with two infants in the study group. Nine infants in the control group and 10 infants in the study group developed hydrocephalus requiring a ventriculoperitoneal shunt or a ventricular catheter reservoir. These differences in the outcome in the two groups are not statistically significant. We conclude that serial lumbar punctures were unsuccessful in prevention of hydrocephalus in this group of preterm infants with intraventricular hemorrhage.", "Treatment of posthaemorrhagic ventricular dilatation by early repeated cerebrospinal fluid taps was compared with conservative management in a randomised controlled trial of 157 infants in 15 centres. Thirty infants died and six moved abroad before follow up. During the first 14 days after randomisation, the early treatment group had five times more taps, and 12 times more cerebrospinal fluid removed. Infection of the cerebrospinal fluid occurred in seven of the early treated and four of the conservatively managed infants. Of survivors, 62% in both groups ultimately had ventricular shunts. Neurodevelopmental assessment of survivors at 12 months was carried out by a single experienced examiner. Of survivors, 103 (85%) had abnormal neuromotor signs and 88 (73%) had disabilities. There was no detectable benefit of early treatment for children who did not have parenchymal lesions at the time they entered the trial. Nearly all those with parenchymal lesions had neuromotor impairment, but early treatment was associated with a significant reduction in other impairments." ]

[ "7149071", "1674295", "6889709", "3897460", "7198209", "6802657", "3479525", "1581445", "7119136" ]

[ "Reduction of cholesterol risk factors by lecithin in patients with Alzheimer's disease.", "Intramuscular desferrioxamine in patients with Alzheimer's disease.", "Lecithin administration in Alzheimer dementia.", "A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease.", "Alzheimer disease: lack of effect of lecithin treatment for 3 months.", "Lecithin treatment of cognitively impaired Parkinson's patients.", "Failure of long term high-dose lecithin to retard progression of early-onset Alzheimer's disease.", "The effect of long-term high dose lecithin on erythrocyte choline transport in Alzheimer patients.", "A dose-ranging study of lecithin in the treatment of primary degenerative dementia (Alzheimer disease)." ]

[ "nan", "Although epidemiological and biochemical evidence suggests that aluminium may be associated with Alzheimer's disease (AD), there is no convincing proof of a causal link for aluminium in disease progression. We have completed a two year, single-blind study to investigate whether the progression of dementia could be slowed by the trivalent ion chelator, desferrioxamine. 48 patients with probable AD were randomly assigned to receive desferrioxamine (125 mg intramuscularly twice daily, 5 days per week, for 24 months), oral placebo (lecithin), or no treatment. No significant differences in baseline measures of intelligence, memory, or speech ability existed between groups. Activities of daily living were assessed and videorecorded at 6, 12, 18, and 24 month intervals. There were no differences in the rate of deterioration of patients receiving either placebo or no treatment. Desferrioxamine treatment led to significant reduction in the rate of decline of daily living skills as assessed by both group means (p = 0.03) and variances (p less than 0.04). The mean rate of decline was twice as rapid for the no-treatment group. Appetite (n = 4) and weight (n = 1) loss were the only reported side-effects. We conclude that sustained administration of desferrioxamine may slow the clinical progression of the dementia associated with AD.", "nan", "The first long-term double-blind placebo controlled trial of high dose lecithin in senile dementia of the Alzheimer type is reported. Fifty one subjects were given 20-25 g/day of purified soya lecithin (containing 90% phosphatidyl plus lysophosphatidyl choline) for six months and followed up for at least a further six months. Plasma choline levels were monitored throughout the treatment period. There were no differences between the placebo group and the lecithin group but there was an improvement in a subgroup of relatively poor compliers. These were older and had intermediate levels of plasma choline. It is suggested that the effects of lecithin are complex but that there may be a \"therapeutic window\" for the effects of lecithin in the condition and that this may be more evident in older patients.", "Eleven outpatients with Alzheimer disease of moderate severity completed a double-blind placebo-controlled crossover trial of lecithin. Each patient received 10 gm three times daily of a placebo for 3 months. Plasma choline levels rose threefold and remained at that level throughout the lecithin administration period. A significant difference between mean baseline scores and treatment scores was found on tests of new learning ability, indicating a practice effect in these tests. However, there were no differences between mean placebo and lecithin scores on any of the psychological test measures.", "To test the effects of lecithin on cognitive deficits associated with Parkinson's disease, sixteen elderly and mentally-impaired outpatients with Parkinson's disease participated in a 9-week double-blind placebo-controlled study. Each patient took a daily dose of approximately 32 g of a commercial lecithin preparation containing 25% phosphatidylcholine, or an equivalent amount of powdered skim milk placebo. Marked clinical improvement was not observed, but some indications of a positive treatment effect were obtained on memory, cognition, and motility tests.", "We conducted a six-month, randomized, double-blind trial of lecithin therapy in early-onset Alzheimer's disease. We hypothesized that such therapy would retard the progression of the clinical and neuropsychological manifestations of this illness. Of the 73 referred patients, 37 met strict requirements for diagnosis and compliance. The 21 placebo and 16 lecithin-treated patients (mean age 63 years) had a comparable degree of severity of dementia (mean Clinical Dementia Rating 1.6). Lecithin therapy produced an increase in mean plasma choline levels from a baseline of 15.9 to 28.8 nmol/ml. Patients were evaluated by the physician using clinical assessments (CDR, Lawton ADL and other rating scales) and by the neuropsychologist who determined the outcome of therapy on a battery of tests (Mini Mental State Examination, Wepman Aphasia Screen, Verbal Fluency Test, Verbal Selective Reminding Test and Spatial Memory Test). Only 6 (37.5%) of the 16 lecithin-treated patients were considered by the neurologist to be clinically stable or improved as compared to 12 (57.1%) of the 21 patients given placebo (difference -19.6%, 95% confidence limits of -51% to 12%). The neuropsychologic scores showed no differences in the stability of the dementing process over time between the lecithin-treated (50.0%) and placebo (47.6%) groups. On the basis of these clinical and neuropsychological findings, it appears that lecithin alone has no important therapeutic effect in early-onset Alzheimer's disease.", "nan", "nan" ]

[ "12196367", "11604444", "7498356", "17341515", "16904951", "16279581", "15173366", "19473813", "12610182", "12538203", "3094776", "10213724", "16279289", "18946893", "18386101", "20484492", "15800312", "16877628", "18245061", "16679344", "19403495", "15485728", "16279272", "7898297", "17148534", "7659635", "1941028", "9376207", "15850856", "18718924", "15617949", "9422014", "10221739", "20367586", "17060222", "2189772", "17848908", "12057880", "19152024", "18166837", "10519499", "11737404", "9104380" ]

[ "Informing breast cancer patients about clinical trials: a randomized clinical trial of an educational booklet.", "Does sending a home safety questionnaire increase recruitment to an injury prevention trial? A randomised controlled trial.", "[The request for consent in clinical research: a randomized study in healthy subjects].", "Effect of using different modes to administer the AUDIT-C on identification of hazardous drinking and acquiescence to trial participation among injured patients.", "A randomised trial of the effects of an additional communication strategy on recruitment into a large-scale, multi-centre trial.", "Is the future for clinical trials internet-based? A cluster randomized clinical trial.", "The influence of risk and monetary payment on the research participation decision making process.", "Publicity does not increase recruitment to falls prevention trials: the results of two quasi-randomized trials.", "Randomized, controlled trial of an easy-to-read informed consent statement for clinical trial participation: a study of the Eastern Cooperative Oncology Group.", "The influence of protocol pain and risk on patients' willingness to consent for clinical studies: a randomized trial.", "Randomised comparison of procedures for obtaining informed consent in clinical trials of treatment for cancer.", "Is recruitment more difficult with a placebo arm in randomised controlled trials? A quasirandomised, interview based study.", "The effects of an open design on trial participant recruitment, compliance and retention--a randomized controlled trial comparison with a blinded, placebo-controlled design.", "Effects of disclosing financial interests on participation in medical research: a randomized vignette trial.", "Effects of disclosing financial interests on attitudes toward clinical research.", "Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.", "Improving accrual of older persons to cancer treatment trials: a randomized trial comparing an educational intervention with standard information: CALGB 360001.", "Impact of privacy legislation on the number and characteristics of people who are recruited for research: a randomised controlled trial.", "Multimedia consent for research in people with schizophrenia and normal subjects: a randomized controlled trial.", "Telephone screening for hazardous drinking among injured patients seen in acute care clinics: feasibility study.", "More information, less understanding: a randomized study on consent issues in neonatal research.", "Telephone reminders are effective in recruiting nonresponding patients to randomized controlled trials.", "A randomized trial of recruitment methods for older African American men in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.", "Cancer patients' decision making and trial-entry preferences: the effects of \"framing\" information about short-term toxicity and long-term survival.", "Design of trials with dying patients: a feasibility study of cluster randomisation versus randomised consent.", "Presenting clinical trial information: a comparison of methods.", "A randomized controlled trial comparing quantitative informed consent formats.", "Evaluation of a video-supplement to informed consent: injection drug users and preventive HIV vaccine efficacy trials.", "Breast cancer prevention in community clinics: will low-income Latina patients participate in clinical trials?", "Optimising recruitment into a study of physical activity in older people: a randomised controlled trial of different approaches.", "Blinding decreased recruitment in a prevention trial of postmenopausal hormone therapy.", "The impact of using a partially randomised patient preference design when evaluating alternative managements for heavy menstrual bleeding.", "Cost effectiveness of screening for clinical trials by research assistants versus senior investigators.", "Improving communication when seeking informed consent: a randomised controlled study of a computer-based method for providing information to prospective clinical trial participants.", "Impact of on-site initiation visits on patient recruitment and data quality in a randomized trial of adjuvant chemotherapy for breast cancer.", "Recruitment in a primary care trial on smoking cessation.", "A randomised controlled study of an audiovisual patient information intervention on informed consent and recruitment to cancer clinical trials.", "Recruitment of Hispanic women to the Women's Health Initiative. the case of Embajadoras in Arizona.", "An educational video to increase clinical trials enrollment among breast cancer patients.", "An educational video to increase clinical trials enrollment among lung cancer patients.", "Randomized trial of informed consent and recruitment for clinical trials in the immediate preoperative period.", "Does an HIV clinical trial information booklet improve patient knowledge and understanding of HIV clinical trials?", "Evaluating the benefits of a patient information video during the informed consent process." ]

[ "To evaluate the impact of an educational booklet on women's knowledge of and willingness to participate in a randomized clinical trial of treatment for breast cancer.\n Women undergoing surgery for newly diagnosed early stage breast cancer were randomized to receive, or not, an information booklet explaining the need for and manner in which randomized trials are conducted.\n Eighty-three women with newly diagnosed early stage breast cancer completed a questionnaire assessing attitudes to random clinical trials (RCTs) and were randomized to receive usual information treatment options provided from their oncologist, or the educational booklet in addition to usual information from their oncologist (42 usual information, 41 booklet). Fewer women who received the clinical trials booklet (40% versus 47%) would consider participating in the hypothetical clinical trial (P = 0.6). Mean knowledge scores increased for both groups; moreover, women who did not receive the booklet showed similar improvements to women who received the booklet [mean difference 0.09, 95% confidence interval (CI) -0.66 to 0.83]. In a multivariate analysis women who would consider participating in the clinical trial were more anxious [odds ratio (OR) 5.9, P = 0.02] had involved lymph nodes (OR 5.8, P = 0.02) and were less influenced by negative aspects of clinical trials (OR 7.7, P = 0.0001). After adjustment for these variables women who received the educational booklet were significantly less likely to consider trial participation (OR 0.22, P = 0.05).\n Educating women about clinical trials in this manner appears ineffective in improving recruitment to RCTs. Women appear to be more influenced by their perception of risk than understanding. This finding has ethical implications for communication of information about RCTs.", "nan", "To compare two strategies of consent requirement (classical informed consent and randomised consent according to Zelen), the Clinical Data Elaboration Centre of South Italy, within the special project Clinical Application of Oncological Research of the National Research Council of Italy (CNR-ACRO) invited healthy people visiting the 7th edition of the scientific exhibition \"Futuro Remoto\" to simulate of being ill and receiving the offer of entering a clinical trial. Within informed consent strategy patients are asked to agree to the randomisation process, while, in the randomised consent, randomised treatment assignment is performed before consent requirement and patients should agree directly to the assigned therapy. Major aims of the study were (a) to compare the strategies in terms of refusal rate to a hypothetical clinical trial, and (b) to estimate whether severity of prognosis affected subjects' decision. 3,217 visiting people participated to the simulation; they were prevalently young, males and with a high level of school education. The study was performed in two different scenarios. In the first one, with one choice option, subject refusing consent could receive standard therapy only; refusal rate was 16% after informed consent and 13.4% after randomised consent (for experimental therapy). In the other scenario, with two choice options, subjects refusing consent could choose the preferred therapy; refusal rate was 20.6% after informed consent, 48.1% after randomised consent (for standard therapy) and 13.4% after randomised consent (for experimental therapy).(ABSTRACT TRUNCATED AT 250 WORDS)", "We compared the effect of three different modes of questionnaire administration on screening for hazardous drinking and acquiescence to trial participation.\n A quasi-randomized controlled trial among injured patients seen in acute care clinics compared self-administered paper-and-pencil, self-administered electronic, and orally-administered interview questionnaires. Outcomes included positive AUDIT-C screens for hazardous drinking, willingness to participate in a (hypothetical) lifestyle intervention trial, and recruitment success. Differences were analyzed with nonlinear mixed models, controlling for age, sex, and facility. Structured interviews with staff explored levers and barriers to screening.\n Of the 370 participants, 22.7% scored > or =4 and 7.8% > or =6 on the AUDIT-C. Electronic questionnaires were more likely than paper questionnaires to identify an AUDIT-C > or =6 (OR = 1.96; 95% CI 1.10-3.48), but not > or =4 (OR = 0.83; 95% CI 0.43-1.62). Oral questionnaires were as likely as paper questionnaires to identify an AUDIT-C > or =4 (OR = 1.00; 95% CI 0.40-2.51) or > or =6 (OR = 1.94; 95% CI 0.83-4.50). Electronic and oral questionnaires were more likely to elicit acquiescence to trial participation (OR = 1.59; 95% CI 1.23-2.07, and OR = 1.66; 95% CI 1.22-2.26, respectively). Oral questionnaires created problems with confidentiality, privacy, and disruption of patient flow, and reduced recruitment success (OR = 0.51; 95% CI 0.42-0.62).\n Among acutely injured patients in clinics who consented to screening, nearly one-fourth reported hazardous drinking. Compared to paper questionnaires, electronic screening produced less social desirability bias and greater acquiescence to trial participation. Oral questionnaires produced greater acquiescence, but barriers to use adversely affected recruitment. Electronic questionnaires may be preferable for screening for hazardous drinking and recruitment into intervention trials in acute care clinics.", "Timely participant recruitment remains a significant challenge for most clinical trials. We evaluated the effects on participant recruitment of communication between the central trial coordinators and the clinical sites in the setting of a large international multi-centre clinical trial. The effects of communication were determined in a single-blind randomised controlled trial involving 167 clinical sites in 19 countries. Clinical sites were randomised to either additional or usual communication strategies - the additional communication group received a communication package based on additional, individually-tailored feedback about recruitment, in addition to the usual correspondence from the central trial coordinators that was provided to the control group. The two study outcomes were the median time to half randomisation target and the median total number of participants randomised per clinical site. Eighty-five clinical centres were randomised to receive additional communication and 82 to receive usual communication. At the conclusion of recruitment, there was no significant difference in the median number of participants randomised per centre between the additional and usual groups (37.5 vs. 37.0, p=0.68). The median time to half randomisation target was lower in the additional communication group compared to the usual group, however this difference did not achieve conventional levels of statistical significance (4.4 months vs. 5.8 months, p=0.08). The findings suggest that the additional communication strategy may be of some incremental benefit in helping sites achieve recruitment targets sooner.", "To compare the efficiency and ease of use of internet data capture compared with conventional paper based data recording in the conduct of a clinical trial.\n Multicentre, cluster randomized clinical trial.\n General practice in the UK.\n Timings for study landmarks, queries, data entry and monitoring time; Investigator Questionnaire Results.\n The internet-derived database was ready for release 33 days after the last patient visit compared with 48 days for the paper-derived database, despite much higher numbers of patients in the internet group. The mean times from visit to data entry were 10.2 (SD 18.9) days and 95.4 (SD 44.6) days respectively (P < 0.01). The mean times from a visit to a query being resolved were 121.4 (SD 58.3) days and 182.1 (SD 58.9) days respectively (P < 0.01). The post-study responses from investigators were positive. Seventy-one percent of centres said they would prefer to use the internet rather than paper CRFs for future studies.\n There were efficiency gains seen with the use of an internet-based system when compared with a paper-based system in terms data entry, query resolution and the time to the release of the database. The investigators' response to the internet system was generally favourable although on average investigators reported increased time spent on the study. Further efficiency might be gained with improved programming, increased investigator familiarity with the internet system, and with newly adapted working practices for sponsors' monitors and database personnel.", "To determine the effects of risk and payment on subjects' willingness to participate, and to examine how payment influences subjects' potential behaviours and risk evaluations.\n A 3 (level of risk) x 3 (level of monetary payment), between subjects, completely randomised factorial design was used. Students enrolled at one of five US pharmacy schools read a recruitment notice and informed consent form for a hypothetical study, and completed a questionnaire. Risk level was manipulated using recruitment notices and informed consent documents from hypothetical biomedical research projects. Payment levels were determined using the payment models evaluated by Dickert and Grady as a guide. Five dependent variables were assessed in the questionnaire: willingness to participate, willingness to participate with no payment, propensity to neglect to tell about restricted activities, propensity to neglect to tell about negative effects, and risk rating.\n Monetary payment had positive effects on respondents' willingness to participate in research, regardless of the level of risk. However, higher monetary payments did not appear to blind respondents to the risks of a study. Payment had some influence on respondents' potential behaviours regarding concealing information about restricted activities. However, payment did not appear to have a significant effect on respondents' propensity to neglect to tell researchers about negative effects.\n Monetary payments appear to do what they are intended to do: make subjects more willing to participate in research. Concerns about payments blinding subjects to risks could not be substantiated in the present study. However, the findings do raise other concerns--notably the potential for payments to diminish the integrity of a study's findings. Future research is critical to make sound decisions about the payment of research subjects.", "To test the effect of publicity on recruitment to a randomized trial. Recruitment is often poor in trials. Publicity within recruitment packs might be an inexpensive method of increasing recruitment. We tested this in two quasi-randomized trials.\n In a primary care setting, within the context of a randomized trial of falls prevention, we allocated participants to receive a newspaper article about the study with their information sheet. The first trial compared one newspaper article against no article; the second compared a more favorably written article against the original.\n In the first study 4,488 participants were allocated into two groups. The response rate was 102 and 97 in the intervention and control groups, respectively (4.55% vs. 4.32%, 95% confidence interval [CI]: -0.98, 1.43); the recruitment rate was 73 and 71, respectively, the difference not being statistically significant. In the second study 2,745 were allocated into two groups with a response rate of 75 and 69 for the control and intervention groups, respectively (5.46% vs. 5.03%, 95% CI: -1.24, 2.09); the recruitment rate was 57 and 54, respectively, the difference not being statistically significant.\n These two large experiments revealed no evidence of effect of publicity on recruitment rates.", "Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population. This study hypothesized that use of an easy-to-read consent statement, when compared with a standard consent statement, will result in higher patient comprehension of the clinical treatment protocol, lower patient anxiety, higher patient satisfaction, and higher patient accrual.\n A randomized controlled trial was conducted in 44 institutions that were members or affiliates of three cooperative oncology groups. Institutions were randomly assigned to administer either an easy-to-read consent statement or the standard consent statement to patients being recruited to participate in selected cancer treatment trials. Telephone interviews were conducted with a total of 207 patients to assess study outcomes.\n Patients in the intervention arm demonstrated significantly lower consent anxiety and higher satisfaction compared with patients in the control arm. Patient comprehension and state anxiety were not affected by the intervention. Accrual rates into the parent studies also did not differ significantly between the two study groups.\n Clinical trial informed consent statements can be modified to be easier to read without omitting critical information. Patient anxiety and satisfaction can be affected by the consent document. The generalizability of these study results is limited by the characteristics of the patient sample. Ninety percent of the sample were white women, and the mean Rapid Estimate of Adult Literacy in Medicine score was approximately 64, indicating a literacy level at or above the ninth grade.", "We tested the hypothesis that the risk or discomfort associated with a clinical trial influence patients' decisions to participate. Simultaneously, we evaluated factors likely to influence patients' decisions such as understanding of the risk and discomfort associated with the study, patient age, educational level, and psychological status. With IRB approval, participants, who believed they were being asked to participate in a real trial, were presented one of three sham protocols: no risk or pain (Control, n = 48), pain but no risk (Pain, n = 51), or risk but no pain (Risk, n = 51). Patients were debriefed at the end of the interview. Our major outcome measures were (a) understanding risk or pain associated with the proposed studies, (b) the extent to which patients felt pressured to participate, and (c) willingness to participate. Whereas understanding was similar in all groups (Control, 68%; Pain, 67%; and Risk, 72%), willingness to participate differed significantly (Control, 64%; Pain, 35%; Risk, 26%; P < 0.001). Patients who understood the level of risk or pain associated with the protocols were twice as likely to participate than those who did not (49% versus 24%; P = 0.003). Nine percent agreed to participate in the risky or painful protocols without understanding the risks involved. Patients who felt pressured did not agree to participate. Thus, the consent process protected patients, although for unexpected reasons. Understanding was poor, but patients who did not understand the risks or pain involved or who felt pressured rarely consented. Consequently, relatively few patients unknowingly agreed to participate in risky or painful studies.", "Methods of obtaining informed consent have evolved differently in Western countries without substantive information on the impact of these different practices on the patients. A randomised study was performed to compare two commonly adopted methods of seeking consent to randomised treatment: an individual approach at the discretion of each doctor and a uniform policy of total disclosure of all relevant information. The impact of both consent procedures on the patient's understanding and anxiety levels and on the doctor-patient relationship was assessed by means of a questionnaire given soon after the consent interview. Fifty seven patients were assigned at random to two groups: to 29 patients an individual approach to seeking consent was adopted and to 28 patients all relevant information was given. Seven patients refused consent to randomised treatment, with slightly more refusals by patients in the total disclosure group (5 v 2, p = 0.25). The main effects of total disclosure of all information compared with an individual approach to seeking consent were: a better understanding of treatment and side effects and of research aspects of the treatments; less willingness to agree to randomised treatment; and increased anxiety. No significant differences were found in patients' perceptions of the doctor-patient relationship. A repeat questionnaire given three to four weeks later no longer showed significant differences between the two groups.", "To investigate whether including a placebo arm in a clinical trial of hormone replacement therapy influenced women's stated willingness to participate.\n Quasirandomised, interview based study. Setting: 10 group practices in the Medical Research Council's General Practice Research Framework.\n 436 postmenopausal women aged 45-64 who had not had a hysterectomy.\n Stated willingness to enter a trial and reasons for the decisions made.\n Of 218 women told about the trial without a placebo arm, 85 (39%) indicated their willingness to enter compared with 65 (30%) of the 218 women told about the trial with the placebo arm (P=0.06). Part of this difference was due to explicit reluctance to take a placebo. Altruism and personal benefit were the reasons most frequently given for wanting to take part in a trial. The reasons most frequently cited for not wanting to take part were reluctance to restart periods, not wanting to take unknown or unnecessary tablets, or not wanting to interfere with present good health.\n For preventive trials the inclusion of a placebo arm may reduce patients' willingness to participate.", "In randomized trials there may be no overriding reason whether or not to have a placebo control.\n We assessed the effects of an open trial design (no placebo and people know what tablets they are given) compared with a blinded, placebo-controlled design on recruitment, compliance and retention within a randomized trial of secondary osteoporotic fracture prevention.\n We undertook a randomized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture, recruited in a UK teaching hospital. Randomization was 2:1 in favour of the blinded, placebo-controlled trial design.\n From 180 eligible participants randomized to receive information based on the open trial design, 134 (74.4%) consented to take part, compared with 233 (65.1%) of 358 people randomized to the blinded, placebo-controlled design (difference 9.4%, 95% confidence interval 1.3-17.4%). Reluctance to take a placebo and the desire to know tablet allocation were reasons given for not taking part in the blinded, placebo-controlled design. There was no significant difference in tablet compliance. Open trial participants were more likely to remain in the trial for one year (difference 13.9%, 95% confidence interval 3.1-24.6%), mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group (difference 23.6%, 95% confidence interval 11.9-35.2%). The odds ratio for reporting an adverse event in the open trial compared to the blinded, placebo-controlled design was 0.64 (95% confidence interval 0.28-1.49), and for reporting a fracture was 0.81 (0.36-1.85).\n We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power, but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial.", "Little is known about the effects of investigators' financial disclosures on potential research participants.\n We conducted a vignette trial in which 470 participants in a telephone survey were randomly assigned to receive a simulated informed consent document that contained 1 of 2 financial disclosures (per capita payments to the research institution or equity ownership by the investigator) or no disclosure. The main outcome measures were trust in medical research and willingness to participate in a hypothetical clinical trial.\n Participants in the equity group reported less willingness to participate than participants in the per capita payments group (P = .01) and the no disclosure group (P = .03). Trust in the investigator was highest in the per capita payments group and lowest in the equity group (P < .001). Trust among participants who received no disclosure was also greater than trust among participants in the equity group (P = .04) but did not differ significantly from trust among participants in the per capita payments group (P = .15). Participants in the equity group made 3 times as many negative comments as participants in the per capita payments group; and 10 participants in the equity group spontaneously said they would not participate in the hypothetical trial because of the financial interest, compared with only 1 such participant from the other groups.\n Although investigators' financial disclosures in research do not substantially affect willingness to participate, potential research participants are more troubled by equity interests than by per capita payments.", "The effects of disclosing financial interests to potential research participants are not well understood.\n To examine the effects of financial interest disclosures on potential research participants' attitudes toward clinical research.\n Computerized experiment conducted with 3,623 adults in the United States with either diabetes mellitus or asthma, grouped by lesser and greater severity. Respondents read a description of a hypothetical clinical trial relevant to their diagnosis that included a financial disclosure statement. Respondents received 1 of 5 disclosure statements.\n Willingness to participate in the hypothetical clinical trial, relative importance of information about the financial interest, change in trust after reading the disclosure statement, surprise regarding the financial interest, and perceived effect of the financial interest on the quality of the clinical trial.\n Willingness to participate in the hypothetical clinical trial did not differ substantially among the types of financial disclosures. Respondents viewed the disclosed information as less important than other factors in deciding to participate. Disclosures were associated with some respondents trusting the researchers less, although trust among some respondents increased. Most respondents were not surprised to learn of financial interests. Researchers owning equity were viewed as more troubling than researchers who were compensated for the costs of research through per capita payments.\n Aside from a researcher holding an equity interest, the disclosure to potential research participants of financial interests in research, as recommended in recent policies, is unlikely to affect willingness to participate in research.", "Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial.\n To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending pound5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants.\n Single blind controlled trials with allocation concealment. Interventions: Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with pound5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures.\n Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6-4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference -0.2 (95% CI -0.6-0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4-6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7-5.2).\n There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic.\n Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a pound5 reimbursement for participants' time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265-273. http://ctj.sagepub.com.", "To design and test a geriatric educational intervention to improve accrual of cancer patients age 65 years and older to cooperative group-sponsored treatment trials.\n Main member institutions of the Cancer and Leukemia Group B (CALGB) and its affiliates were randomly assigned to receive standard information (n = 73) or educational intervention (n = 53). Standard information included CALGB Web site access and periodic notification about existing trials. The geriatric educational intervention included standard information plus: (1) an educational seminar; (2) educational materials; (3) a list of available protocols for use on charts; (4) a monthly e-mail and mail reminders for 1 year; and (5) a case discussion seminar. The main outcome was percentage of accrual of older persons to phase II and III treatment protocols after study initiation compared with baseline.\n There were 3,032 patients entered onto trials in the baseline year, and 2,160 and 1,239 during the 2 years postintervention, respectively. Overall percentage of accrual of older patients was 37% at baseline, and 33% and 31% during the first and second years after intervention. There was no improvement in accrual in the intervention versus control arm: 36% v 32% in the first year and 31% v 31% in the second year.\n Accrual of older patients was not increased by this intervention. Reasons for lack of effect include low intervention intensity, high baseline accrual rates, and closure of several high-accruing protocols during the study. More intense and multifaceted approaches will be needed to change physician (and patient) behavior and to increase accrual of older persons to clinical trials.", "Privacy laws have recently created restrictions on how researchers can approach study participants. Method: In a randomised trial of 152 patients, 50-74 years old, in a family practice, 60 were randomly selected to opt-out and 92 to opt-in methods. Patients were sent an introductory letter by their doctor in two phases, opt-out before and opt-in after introduction of the new Privacy Legislation in December 2001. Opt-out patients were contacted by researchers. Opt-in patients were contacted if patients responded by email, free telephone number or a reply-paid card.\n Opt-in recruited fewer patients (47%; 43/92) after invitation compared with opt-out (67%; 40/60); (-20%; [-4% to -36%]). No proportional difference in recruitment was found between opt-in and opt-out groups varied by age, sex or socioeconomic status. The opt-in group had significantly more people in active decision-making roles (+30%; [10% to 50%]; p = 0.003). Non-significant trends were observed towards opt-in being less likely to include people with lower education (-11.8%; [-30% to 6.4%]; p = 0.13) and people who were not screened (-19.1%; [-40.1% to 1.9%]; p = 0.08). Opt-in was more likely to recruit people with a family history of colorectal cancer (+12.7%; [-2.8%, 28.2%]; p = 0.12).\n The number of participants required to be approached was markedly increased in opt-in recruitment. Existing participants (eg, screening attendees) with a vested interest such as increased risk, and those preferring an active role in health decision making and with less education were likely to be recruited in opt-in. Research costs and generalisability are affected by implementing privacy legislation.", "Limitations of printed, text-based, consent forms have long been documented and may be particularly problematic for persons at risk for impaired decision-making capacity, such as those with schizophrenia. We conducted a randomized controlled comparison of the effectiveness of a multimedia vs routine consent procedure (augmented with a 10-minute control video presentation) as a means of enhancing comprehension among 128 middle-aged and older persons with schizophrenia and 60 healthy comparison subjects. The primary outcome measure was manifest decisional capacity (understanding, appreciation, reasoning, and expression of choice) for participation in a (hypothetical) clinical drug trial, as measured with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and the University of California San Diego (UCSD) Brief Assessment for Capacity to Consent (UBACC). The MacCAT-CR and UBACC were administered by research assistants kept blind to consent condition. Additional assessments included standardized measures of psychopathology and cognitive functioning. Relative to patients in the routine consent condition, schizophrenia patients receiving multimedia consent had significantly better scores on the UBACC and on the MacCAT-CR understanding and expression of choice subscales and were significantly more likely to be categorized as being capable to consent than those in the routine consent condition (as categorized with several previously established criteria). Among the healthy subjects, there were few significant effects of consent condition. These findings suggest that multimedia consent procedures may be a valuable consent aid that should be considered for use when enrolling participants at risk for impaired decisional capacity, particularly for complex and/or high-risk research protocols.", "We evaluated the effectiveness of telephoning injured patients after discharge, compared with contacting them in the clinic during the acute care visit, for screening for hazardous drinking and eliciting willingness to participate in a lifestyle intervention trial.\n We conducted a quasi-randomized controlled trial among acutely injured adult patients in trauma and acute care clinics, assigning telephone and clinic screening strategies systematically by week. During telephone weeks, we mailed study information to patients identified from computerized records, then telephoned them. During clinic weeks, researchers recruited patients awaiting care. We screened for hazardous drinking using the AUDIT-C (Alcohol Use Disorders Identification Test-C). We examined the proportion of all injured adult patients who were screened, the proportion of screened patients with hazardous drinking (AUDIT-C score >or=4), and the proportion willing to participate in a (hypothetical) lifestyle intervention trial. Differences were analysed with non-linear mixed models using generalized estimating equations, controlling for age, sex, and facility. Levers and barriers to screening were explored through structured interviews with research staff.\n We enrolled 29% (469/1,609) of all injured adult patients and 76% of injured patients contacted and found to be eligible. Of screened patients, 23.1% screened positive for hazardous drinking. Telephone and clinic contact were equally effective for screening patients (OR = 1.05; 95% CI = 0.59-1.87), identifying hazardous drinking (OR=0.97; 95% CI = 0.54-1.74), and eliciting willingness to participate in an intervention trial (OR=1.49; 95% CI = 0.97-2.30). Clinic site modified results: telephone was more effective than clinic contact for screening urban patients (OR=1.99; 95% CI = 1.36-2.93), but less effective for screening suburban patients (OR = 0.70; 95% CI = 0.69-0.71). Barriers to clinic screening included lack of clinic staff support, time constraints, and difficulty recruiting elderly or acutely distressed patients. Barriers to telephone screening included erroneous contact information and failure to answer the telephone.\n Telephone screening is a feasible and efficient method for screening moderately injured adult patients for hazardous drinking, but characteristics of the clinical site (including personnel) influence its effectiveness. Trauma and acute care clinics are likely to be fruitful sites for identification of patients with hazardous drinking, whether for enrollment into brief intervention trials or treatment programmes.", "Valid consent for research requires comprehensive and understandable information to be disclosed to participants. The way that information is shared varies, but regulatory bodies usually determine style. Some reports have suggested that although information may be all-inclusive, it does little to support understanding.\n To explore the impact of various information-sharing approaches on parents' understanding of a research study and the validity of their consent.\n This was a randomized, controlled trial. Parents of immature but well infants admitted to a large tertiary NICU in Edinburgh, Scotland, were randomly assigned within 72 hours of their infant's admission to receive 1 of 2 information leaflets, with or without a standardized verbal explanation, for a hypothetical intensive care research study. The leaflets differed in length and in the amount of detail in which the study process, risks, benefits, and patient rights were described. A questionnaire was used to elicit understanding about the purpose of the research, design of the study, procedures involved, and the consent process.\n Forty-one parents participated in the study. Those who received the longer leaflet without verbal explanation gained only limited understanding of the purpose of the research. The procedures involved in the study were understood better by those who received the shorter leaflet. Issues relating to consent and study design were readily understood in all groups. Irrespective of documentation style, verbal explanation significantly improved understanding. Differences in understanding had little effect on whether a parent would enroll his or her infant into the study.\n Verbal explanation significantly enhances understanding of the research process for participants regardless of the style of written documentation. However, shorter written information may lead to better understanding than lengthy, more complex documentation.", "Studies investigating means of recruiting participants to randomized controlled trials (RCTs) are sparse. We investigated the effects of telephone reminders as a recruitment strategy.\n Sick-listed employees received a written invitation to participate in a study comparing standard treatments with a solution-focused follow-up and were randomly allocated to an intervention or control group (n=703). Those who did not respond within 2 weeks received either 'no reminder' (n=242) or 'attempted telephone reminder' (n=256). Outcome was enrollment to the RCT.\n An intention to recruit analysis revealed no significant differences between the groups (P=.229). An intention to phone analysis among nonresponders revealed significant differences between 'no reminder' (recruited 4.5%) and 'attempted telephone reminder' (recruited 12.1%) (P=.003, odds ratio 2.89, 95% confidence interval [CI] 1.42-5.90). An analysis of numbers needed to phone showed that to recruit one more person in this group of nonresponders, we needed to phone 13 persons (95% CI=8-33).\n Systematic use of telephone calls can increase the recruitment rate among nonresponders in RCTs.", "Incidence rates for many types of cancer are higher among African American men than in the general population, yet African American men are less likely to participate in cancer screening trials. This paper describes the outcomes of a randomized trial (the AAMEN Project) designed to recruit African American men aged 55-74 years to a prostate, lung and colorectal cancer screening trial.\n The recruitment interventions address four types of barriers to clinical trial participation: sociocultural barriers, economic barriers, individual barriers and barriers inherent in study design. Subjects were randomized to a control group or one of three increasingly intensive intervention arms, which used different combinations of mail, phone and in person church-based recruitment.\n Of the 39,432 African American men residing in the geographically defined study population (southeastern Michigan and northern Ohio), 17,770 men (45%) could be contacted, and 12,400 (31% of 39,432) were found to be eligible to participate. No statistically significant differences in age, education or income level were found among participants in the four study arms. A significantly greater enrollment yield (3.9%) was seen in the most intensive, church-based intervention arm, compared to the enrollment yields in the other two intervention arms (2.5 and 2.8%) or the control group (2.9%) (P < 0.01).\n The intervention that involved the highest rate of face-to-face contact with the study participants produced the highest enrollment yield, but several strategies that were thought could improve yield had no effect. These findings, which are consistent with current literature on population-based recruitment, should facilitate the development of future recruitment efforts involving older African American men.", "The study purpose was to determine whether the framing of treatment information influenced patients' reported preferences for participating in treatment decision making and for trial entry. Ninety cancer patients read either neutrally-, positively-, or negatively-framed information about a chemotherapeutic treatment, then indicated their preferences for participating in the treatment decision, and whether they would participate in a clinical trial incorporating this protocol. There was no difference across information groups in preferences for participating in treatment decision making or willingness to enter such a clinical trial. Preference for participation in treatment decision making was significantly related to age (t = 2.54; p = 0.022), sex (x2 = 3.89; p = 0.05), and education (t = 2.54; p = 0.018); trial entry preferences were unrelated to these demographic variables. These results imply that, in this clinical context, attitudes towards participation in treatment decision making may be associated with characteristics of the patient, and attitudes towards trial entry may be dependent upon the clinical characteristics of a particular trial, but neither set of attitudes is influenced by the framing of protocol information.", "There is little rigorous evidence to underpin clinical guidelines for palliative care. However, research in palliative care is difficult, especially with dying patients. Consent is a major issue, since staff do not wish to invite dying patients to participate in trials. We, therefore, conducted a feasibility study in two units within the North West Wales NHS Trust. We explored two novel approaches to research in palliative care -cluster randomisation and randomised consent. All patients admitted to the two units during the study were asked for permission to use their data for research. We allocated the two units, at random, to use cluster randomisation or randomised consent for three months, and then to crossover to the other design. Of 24 patients dying during cluster-randomised phases, 13 gave consent on admission to use their data and were, thus, eligible to enter the trial; however, defined eligibility criteria reduced these to six active participants. Of 29 patients dying during randomised consent phases, seven gave consent on admission to use their data; although two were eligible for randomisation, neither entered the trial. We judge that cluster randomisation is the more effective design for research with dying patients. Computer simulation, based on data from 1500 dying patients on the Welsh Integrated Care Pathway, shows that crossover cluster trials need much smaller samples than simple cluster trials. Furthermore, this study has shown that crossover cluster trials are entirely feasible. We recommend a 'definitive' trial to test the crossover design more widely.", "The study objective was to assess the relative effects of 2 approaches to teaching about a clinical trial, in terms of patients' satisfaction, information understanding, and whether or not they would enter such a trial. One hundred patients receiving radiation therapy for a variety of cancer diagnoses were randomized to receive information about a hypothetical trial, either by audio tape or interactive computer program. A day later, information understanding was assessed. One week later, method satisfaction and whether respondents would enter such a trial were assessed. There were no differences in understanding or satisfaction. Members of the computer program group tended to report a more positive attitude towards trial entry (chi 2 = 4.0; 1 df; P = 0.05). Overall, refusers tended to be women with higher understanding scores. The results suggest that teaching with interactive components might not adversely affect trial accrual. Further work involving an actual trial entry decision is merited; the sex of the respondent should be controlled in designing this future work.", "Informed consent has been indirectly studied only in settings that do not replicate the actual consent process. We designed a sham study and randomly allocated adult ambulatory patients to receive one of two consent forms: Consent A (n = 52) described a randomized trial of usual treatment vs a new medication that \"may work twice as fast as the usual treatment\"; or Consent B (n = 48) that described a randomized trial of a new medication that \"may work half as fast as the usual treatment\". Patients randomized to Consent A were more likely to consent than those randomized to Consent B (consent rate A = 67%, consent rate B = 42%, p less than 0.01). Among patients who cited quantitative information, the difference in consent rate was even more marked (95% vs 36%, p less than 0.001); patients who did not cite quantitative information had equivalent consent rates. Patients who perceived minimal or severe symptoms had lower consent rates than those with mid-range symptom scores (chi 2(2) = 8.35, p = 0.015). Patients who recognize quantitative information will use it to make informed consent decisions.", "We evaluate the impact of a videotape specially produced to supplement written information about preventive HIV vaccine trials. One hundred eighty-six injection drug users were randomly assigned to an education session in which either: (a) a pamphlet was reviewed before a brief discussion period or (b) the videotape was watched prior to reviewing the pamphlet and participating in the discussion. The relationship among retention of information, trust in government, and willingness to participate in a vaccine trial was tested before the presentation of information, immediately after, and 1 month later. Results indicate that both methods produced significant increases in knowledge immediately after information presentation, but only the video-supplemented group retained the information 1 month later. Subjects receiving the video supplement also showed a significant increase in trust at the first posttest period, but this increase was not maintained 1 month later. Regardless of group assignment or evaluation point, willingness to participate was not associated with knowledge but was associated with trust in government.", "Latinas have low rates of participation in breast cancer prevention trials. We evaluated the feasibility and effectiveness of a randomized trial of brief counseling and print materials compared to print materials alone to increase intent to participate in a breast cancer prevention trial.\n We enrolled 450 women Spanish-speaking women from three urban community primary care clinics. The outcome was intent, defined as might, probably, or definitely would enroll in the trial. We also examined results using a more stringent definition restricted to probably and definitely intend to participate.\n The trial was feasible within these busy clinics, and 96% of women agreed to participate. The level of breast cancer knowledge was fairly high (66% correct answers), but understanding about clinical trials was lower (40.5% correct answers). Using the less stringent criteria for intent, 72% of women stated that they intended to enroll in the STAR trial if eligible, but rates of intent decreased to 52% with framing that included medication side effects and 45% if uterine cancer was mentioned (P < 0.01 for trend). Using the more stringent definition, slightly fewer than half of the women indicated an interest in participating, with the same trend towards decreasing intent with increasing presentation of side effects. The intervention was only effective using the less stringent definition and if no side effects were mentioned (77% intent vs. 67% in the intervention and control groups, respectively, P = 0.03). Intention was independently associated with greater worry about breast cancer and younger age, but not acculturation or knowledge.\n Latina women are interested in participating in clinical trials to prevent breast cancer, although interest declines with increasing discussion of side effects. Unfortunately, brief education only increased rates of intention using the least stringent definition and when no side effects were presented in framing the question. Future work should focus on qualitative research to understand the theoretical foundations of preventive health behaviors in this population.", "physical activity studies in older people often have poor recruitment. Including a questionnaire with the invitation would provide information about non-participants and selection bias, but could reduce recruitment. Telephone contact might encourage participation.\n to test the effects of different strategies for recruitment into a study of physical activity in older people.\n factorial randomised controlled trial. Randomisation by household into four groups: telephone contact plus questionnaire, telephone contact only, questionnaire only, neither.\n primary care, Oxfordshire, United Kingdom.\n 560 patients > or = 65 years randomly selected after exclusions.\n questionnaire to assess health, functional ability and physical activity. Telephone contact by the research nurse a week after sending study information.\n recruitment into physical activity study.\n telephone contact increased recruitment: contact 47.9% (134/280), no contact 37.9% (106/280), difference (adjusted for the clustering effect of household) 10.0% (95% CI 0.2-19.8). Questionnaire inclusion did not significantly reduce recruitment: no questionnaire 44.3% (124/280) questionnaire 41.4% (116/280) difference -2.9% (95% CI -12.7-7.0).\n telephone contact significantly increased recruitment and should be considered in studies where recruitment may be low. While inclusion of a questionnaire provided valuable information on non-participants and did not significantly reduce recruitment, an adverse recruitment effect could not be excluded.", "To compare the effect of blind design (active drug and placebo) and nonblind design (active drug and no treatment) on recruitment.\n A primary prevention trial with postmenopausal hormone therapy in Estonia.\n Women who were eligible and willing to participate on the basis of the questionnaire survey were randomized into blind and nonblind groups. Recruitment rates are based on record keeping, and reasons for participating were requested in the first-year follow-up.\n The recruitment was 30% higher in the nonblind group: of the 4,295 women invited, 37% (95% confidence interval CI=35-39%) in the blind group and 48% (95% CI=46-49%) in the nonblind group were recruited. In both groups, once randomized, most of the losses were women who did not attend the first clinical examination: 49% (blind; 95% CI=47-51%) and 40% (nonblind; 95% CI=38-42%). The rest were found ineligible or lost their interest during clinical examinations. The reasons for joining the trial were relatively similar in the two groups.\n Blinding decreased women's interest in joining a long-term preventive trial. Women's reasons for joining the trial were not influenced by blinding.", "To identify the advantages and disadvantages of using a partially randomised patient preference design rather than a conventional randomised controlled design when evaluating alternative managements for heavy menstrual bleeding.\n Randomised controlled comparison of two clinical trial designs with subsequent follow up of the cohorts of women generated.\n Women attending a general gynaecology clinic for the first time because of heavy menstrual bleeding.\n Partially randomised patient preference clinical trial design and conventional randomised controlled design.\n Overall participation; participation in randomised clinical trial of medical management compared with transcervical surgical resection of the endometrium; prognostic characteristics (socio-demographic and Short Form 36) of clinical trial groups; outcomes (clinical and Short Form 36) of clinical trial groups.\n Overall, more women participated in the partially randomised patient preference design (130/135 vs 97/138; difference 27%, 95% CI 18% to 34%) but there was no difference in the numbers who agreed to be randomised (90/135 vs 97/138; difference-3%, 95% CI-15% to 7%). Women who chose medical management tended to have better general health, to be less restricted by their menstrual problems, with fewer having been previously treated by their general practitioner. Those who chose transcervical resection of the endometrium had all tried medical management and had higher bleeding scores. Follow up satisfactions and acceptability rates, and Short Form 36 scores were highest after transcervical resection of the endometrium, whether chosen or randomised. Acceptability and a desire to continue the same treatment was greater among those who chose medical management than those randomly allocated it.\n Use of the partially randomised patient preference design did not affect recruitment to the randomised controlled trial suggesting that a conventionally designed trial would not be biased by motivational factors in this context. Data from the preference groups informed the generalisability of the results but did tend to confirm conclusions that anyway reasonably followed from the randomised controlled trial. The extra resource implications of using the partially randomised patient preference design were significant reflecting the additional 40% who participated and the extra analyses entailed.", "This study evaluates the relationship between interviewer level of experience and the positive predictive value and cost of telephone screening of subjects for randomized clinical trials. This is a previously uninvestigated area. Respondents to advertisements for chronic depression treatment research received brief, semi-structured telephone interviews (N = 347) either by research assistants (RAs) or by a senior investigator (SI). Those who met criteria based on the phone interview were then interviewed in person using the SCID-P. The RAs did not significantly differ from the SI in the proportion of phone screen positives who were also SCID positive or the proportion of phone screen positives who were randomized. While the SI performed phone interviews significantly faster than the RAs, the SI's higher salary generated a phone screening cost per randomized subject 56% more than that of RAs. The results suggest that trained research assistants are more cost effective than senior investigators for initial screening of depressed patients for research protocols. Further studies are needed to determine whether the findings reported would generalize to other research settings or patient populations.", "To assess the efficacy, with respect to participant understanding of information, of a computer-based approach to communication about complex, technical issues that commonly arise when seeking informed consent for clinical research trials.\n An open, randomised controlled study of 60 patients with diabetes mellitus, aged 27-70 years, recruited between August 2006 and October 2007 from the Department of Diabetes and Endocrinology at the Alfred Hospital and Baker IDI Heart and Diabetes Institute, Melbourne.\n Participants were asked to read information about a mock study via a computer-based presentation (n = 30) or a conventional paper-based information statement (n = 30). The computer-based presentation contained visual aids, including diagrams, video, hyperlinks and quiz pages.\n Understanding of information as assessed by quantitative and qualitative means.\n Assessment scores used to measure level of understanding were significantly higher in the group that completed the computer-based task than the group that completed the paper-based task (82% v 73%; P = 0.005). More participants in the group that completed the computer-based task expressed interest in taking part in the mock study (23 v 17 participants; P = 0.01). Most participants from both groups preferred the idea of a computer-based presentation to the paper-based statement (21 in the computer-based task group, 18 in the paper-based task group).\n A computer-based method of providing information may help overcome existing deficiencies in communication about clinical research, and may reduce costs and improve efficiency in recruiting participants for clinical trials.", "To provide empirical evidence on the impact of on-site initiation visits on the following outcomes: patient recruitment, quantity and quality of data submitted to the trial coordinating office, and patients' follow-up time.\n This methodological study was performed as part of a randomized trial comparing two combination chemotherapies for adjuvant treatment of breast cancer. Centers participating to the trial were randomized to either receive systematic on-site visits (Visited group), or not (Non-visited group).\n The study was terminated after two years, while the main randomized trial continued. Of the 135 centers that had expressed an interest in the trial, only 69 randomized at least one patient (35/68 in the Visited group, 34/67 in the Non-visited group). Almost two-thirds of the patients were entered by 17 centers (10 in the Visited group, seven in the Non-visited group) that accrued more than 10 patients each. None of the prespecified outcomes favored the group of centers submitted to on-site initiation visits (ie, mean number of queries par patient: 6.1 +/- 9.7 versus 5.4 +/- 6.4, respectively for the Visited and Non-visited groups). Spontaneous transmittal of case report forms, although required by protocol, was low in both randomized groups (mean number of pages per patient: 1.5 +/- 2.0 versus 2.1 +/- 2.3, respectively), with investigators submitting about one-third of the expected forms on time (29% and 39%, respectively).\n This study could not evaluate the impact of repeated on-site visits on clinical outcomes.\n Systematic on-site initiation visits did not contribute significantly to this clinical trial.", "The purpose of this study was to describe and compare the rates of recruitment during a randomized clinical trial on smoking cessation in two primary care practices. One site was a five-physician private family practice setting with about 15,000 patients. During 34 days, 576 patients were screened, of whom 22% were smokers. Among the smokers screened, 54% consented, 33% refused consent, and 13% were called in too early to consent. The other site was a six-physician academic medical practice with about 16,000 patients. During 53 days, 1,692 subjects were screened, of whom 16.2% were smokers. Among the smokers, 19% consented, 81% refused consent, and none were called in early. The enrollment of smokers was 3.3 times greater in the private practice than the academic practice. At the first site, study personnel screened 26.6 subjects per day, whereas the practice receptionist screened only 13.4 subjects per day (P less than .01). A randomized trial of having subjects read the informed consent versus having study personnel read it to them showed no differences in recruitment. The data suggest that private practices may have greater potential for subject recruitment than academic sites, that using study personnel improves recruitment, and that having study personnel actively involved in informed consent does not improve recruitment.", "Recruitment to cancer clinical trials needs to be improved, as does patient knowledge and understanding about clinical trials, in order for patients to make an informed choice about whether or not to take part. Audiovisual patient information (AVPI) has been shown to improve knowledge and understanding in various areas of practice, but there is limited information about its effect in the cancer clinical trial setting, particularly in relation to consent rates. In this study, 173 patients were randomised to receive either the AVPI, in addition to the standard trial-specific written information, or the written information alone. There was no difference in clinical trial recruitment rates between the two groups with similar study entry rates: 72.1% in the AVPI group and 75.9% in the standard information group. The estimated odds ratio for refusal (intervention/no intervention) was 1.19 (95% CI 0.55-2.58, P=0.661). Knowledge scores increased more in the AVPI group compared to the standard group (P=0.0072). The change in anxiety score between the arms was also statistically significant (P=0.011) with anxiety improving in the intervention arm more than in the no intervention arm. Audiovisual patient information was shown to be a useful tool in improving patient knowledge and anxiety, but further work is necessary in relation to its effect on clinical trial recruitment rates.", "This study examined the use of lay advocates (i.e., women enrolled in a study who advocate to others) to improve recruitment among Hispanic women in the Arizona recruitment sites for a large-scale, national prevention study, the Women's Health Initiative (WHI). We examined whether trained, Hispanic lay advocates (called Embajadoras) brought more women into the study than a matched group of Hispanic and Anglo enrollees in the WHI who were supplied with brochures. Fifty-six Hispanic participants in the WHI were randomized to receive training or no training on advocacy, and continued to meet quarterly for 18 months. Also, 42 Anglo women were assigned to control. All groups received brochures to use for advocating the WHI. The number of women referred and enrolled was tracked as well as other factors expected to influence outcomes. Embajadoras were more successful at referral and enrollment than untrained Hispanic women and more successful at enrollment than untrained Anglo controls. Embajadoras were also found to distribute significantly more brochures than control groups. Therefore, a culturally aligned training program to encourage current Hispanic participants in a clinical trial to advocate the study to others may be an effective way to boost referrals and enrollments. Other potential influences on enrollment or referral success could not be determined due to the small sample size. Further study is needed to examine the best methods to encourage enrollment for women referred to the study.", "Only 3% of women with breast cancer participate in cancer clinical trials nationwide. The lack of awareness about clinical trials is a significant barrier towards clinical trials participation. A study was conducted at a large urban Comprehensive Cancer Center to test (1) the effectiveness of an 18-min educational video on improving attitudes toward clinical trials and trials enrollment among new breast cancer patients seen at the Karmanos Cancer Institute, and (2) to assess racial differences in attitudes regarding clinical trials. Participants were randomized to either the educational intervention prior to their first oncology clinic appointment or to standard care. A baseline and 2-week post-intervention survey to assess attitudes toward clinical trials participation was completed by participants. Of 218 subjects recruited, 196 (55% white vs. 45% African American (AA)) eligible patients were included in the analysis. A small increase in therapeutic clinical trial enrollment was observed in the intervention arm but was not statistically significant (10.4% vs. 6.1%; P = 0.277). The intervention also did not result in a clear improvement in patients' attitudes toward clinical trials at posttest. However, a lower enrollment rate for the AA women was noted after adjusting for stage (OR = 0.282, P = 0.049). Significantly more negative scores were noted in 3 out of the 5 baseline attitudinal scales for AA women. The educational video did not significantly increase enrollment in breast cancer clinical trials. The findings that AA women had significantly more negative attitudes toward clinical trials than white women may partially explain the racial disparity in enrollment. An educational video remains a simple and cost-effective way to educate patients. Future studies should focus on designing a new educational video to specifically target cultural and attitudinal barriers in the AA population to more effectively change attitudes and increase trial enrollment.", "Only 3 to 5% of new adult cancer patients participate in clinical trials nationwide. The lack of knowledge and awareness about clinical trials is a significant barrier to clinical trials participation. A randomized trial was conducted to test the effect of an educational video on positively changing patients' knowledge and attitudes regarding clinical trials and thereby increasing enrollment rates.\n Lung cancer patients were randomized to viewing either an 18-minute video about clinical trials before first clinic appointment or to standard care. Participants completed a baseline and 2-week postintervention survey to assess their knowledge and attitudes toward trials participation. Fisher's exact test tests, t tests, and regression were used to compare patient characteristics and outcomes between arms.\n Of 145 subjects randomized, 126 (63/arm) satisfied all inclusion criteria and were included in the analysis. A linear regression showed that the video intervention was significantly associated with patients' self-assessed likelihood to enroll score measured at 2-week follow-up (p = 0.019). Although statistically insignificant, enrollment rates were found to be higher in the intervention arm for therapeutic trials alone (17.5% versus 11.1%) and for therapeutic and nontherapeutic trials combined (25.4% versus 15.9%).\n The brief educational video seems to be effective in positively changing lung cancer patients' attitudes about participation in clinical trials. Higher enrollment rates were also observed in the intervention group but the differences did not reach statistical significance. These findings suggest a potential impact of the educational video on clinical trial enrollment; however, larger studies are needed to confirm these findings.", "The standard process of obtaining informed consent sometimes prevents physicians or patients from participating in clinical trials, partly because they are concerned about eventual treatment allocation or the physician is concerned the patient might harbor some uncertainty about the best treatment. Alternative randomization methods have been advocated that may address these and other concerns.\n After institutional ethics committee gave its approval, the authors interviewed 770 patients before operation and asked them to consider enrolling in a mock anesthesia trial. Patients were allocated randomly to one of five methods of randomization and consent: one-sided informed consent (the most common approach), prerandomized consent to experimental treatment, prerandomized consent to standard treatment, one-sided physician-modified informed consent, or one-sided patient-modified informed consent. Recruitment rates were compared and sociodemographic and perioperative predictors of recruitment were identified.\n The randomization method did not result in any significant difference in recruitment rates: one-sided informed consent, 55.6%; prerandomized consent to experimental treatment, 53.3%; prerandomized consent to standard treatment, 53%; one-sided physician-modified informed consent, 60.7%; and one-sided patient-modified informed consent, 56.7% (P = 0.66). Multivariate predictors of recruitment were patient age >45 yr (odds ratio, 1.44; 95% confidence interval [CI], 1.08 to 1.93), English-speaking at home (1.49; 1.0 to 2.21), and male researcher-male patient interaction (1.37; 1.20 to 1.57).\n No evidence emerged that alternative randomization and consent designs resulted in increased recruitment rates compared with simple one-sided informed consent for a sham anesthesia trial in patients awaiting elective surgery. Older, male patients were more likely to provide consent.", "To evaluate the impact of an information booklet on HIV clinical trials, Clinical Trials in HIV and AIDS: Information For People Who Are Thinking About Joining a Trial, in addition to the standard trial information (SI) on patients' knowledge; understanding and attitudes about clinical trials; and to investigate patients' motivations and reasons for enrolling or not enrolling in a clinical trial.\n Fifty HIV-1 positive patients who attended the HIV clinic at a west London hospital were randomized to receive either SI alone (n = 27) or SI and a 16 page information booklet explaining the principles and procedures of HIV clinical trials (n = 23). A self-administered questionnaire was used at baseline to assess past experience and attitudes to clinical trials (10 questions), knowledge and understanding of HIV treatments (8 questions) and clinical trials (11 questions). At 2-6 months after randomization, a second interviewer-administered questionnaire addressed the patient's assessment of the usefulness and comprehensiveness of the information provided by the SI and information booklet, whether or not the patient had enrolled in a clinical trial and reasons for enrolling/not enrolling, knowledge of specific aspects of the trial protocol the patient was eligible to join (13 questions) and general knowledge of clinical trial procedures (repeat of 11 baseline questions). Changes in the attitudes and scores on knowledge and understanding of clinical trials were compared for the two groups.\n In both groups, patient knowledge of clinical trial procedures improved significantly over the study period. The median score increased from 30 at baseline to 35/44 at follow-up (SI only) vs. 24-31/44 (SI plus booklet), but this did not differ significantly between the two groups. However, knowledge of the specific trial protocol was poor [median score 13/25, interquartile range (IQR) 8-14], and there was no difference in the scores for the two groups. The prime motivations for joining a clinical trial were to benefit personal health and to gain access to new treatments. Potential side-effects were the main concern of prospective trial participants.\n This small trial shows that, while the patients' general knowledge and understanding of clinical trials improved over time, this was not improved by the information booklet and recollection of the details of the relevant trial protocol remained poor.", "The study objective was to evaluate the effect of a patient information video during the informed consent process of a perinatal trial. Ninety women, between 19 and 33 weeks gestation, were randomised to receive written information about this perinatal trial and watch an information video or to receive written information only. Participants completed a questionnaire immediately after entry and 2-4 weeks later assessing knowledge of; feelings about the worth of; and willingness for future participation in the perinatal trial. When initially asked, more women who watched the video thought they would consent to the study (chi 2 = 6.3; df = 1; P = 0.01). No differences in knowledge about the perinatal trial were found initially, but 2-4 weeks later more knowledge had been retained by women who had watched the video (chi 2 = 6.7; df = 1; P = 0.01). These results suggest that a patient information video combined with an information sheet may result in greater participation in a research trial and may increase women's knowledge of a specific health problem and related research trial." ]

[ "9200356", "6502311" ]

[ "Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome.", "Prevention of bronchopulmonary dysplasia by administration of bovine superoxide dismutase in preterm infants with respiratory distress syndrome." ]

[ "To examine the safety and pharmacokinetics of multiple intratracheal (IT) doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome who are at risk for developing bronchopulmonary dysplasia (BPD). Methods. Thirty-three infants (700 to 1300 g) were randomized and blindly received saline, 2.5 mg/kg or 5 mg/kg rhSOD IT within 2 hours of surfactant administration. Infants were treated every 48 hours (as long as endotracheal intubation was required) up to 7 doses. Serial blood and urine studies, chest radiographs, neurosonograms, SOD concentration and activity measurements, and tracheal aspirate (TA) inflammatory markers were assessed throughout the 28-day study.\n SOD concentrations in serum (0.1 [0.05/0.15] microg/mL-geometric mean with lower/upper confidence intervals), tracheal aspirates (TA) (0.2 [0.1/0.3] microg/mL) and urine (0.3 [0.2/0.4] microg/mL) were similar at baseline in all 3 groups and did not change significantly in the placebo group. In the rhSOD treatment groups, SOD concentrations were increased on day 3 and did not change significantly thereafter over the 14-day dosing period (also measured on days 5, 7, and 13). SOD concentrations averaged 0.4 [0.3/0.5] microg/mL in serum, 0.8 [0.6/1.2] microg/mL in TA and 1.1 [1.0/1.3] microg/mL in urine for the low-dose group and 0.6 [0.5/0.7] microg/mL in serum, 1.1 [0.9/1.5] microg/mL in TA, and 2.2 [1.6/2.9] microg/mL in urine for the high-dose group over the 14-day dosing period. Enzyme activity directly correlated with SOD concentration and rhSOD was active even when excreted in urine. TA markers of acute lung injury (neutrophil chemotactic activity, albumin concentration) were lower in the rhSOD agroups compared with placebo. No significant differences in any clinical outcome variable were noted between groups.\n These data indicate that multiple IT doses of rhSOD increase the concentration and activity of the enzyme in serum, TA and urine, reduce TA lung injury markers and are well-tolerated. Further clinical trials examining the efficacy of rhSOD in the prevention of BPD are warranted.", "The effectiveness of bovine superoxide dismutase (SOD) in the prevention of bronchopulmonary dysplasia was evaluated in a prospective double-blind controlled study in 45 neonates (mean gestational age 28.7 weeks, mean weight 1154 gm) with severe respiratory distress syndrome. All were ventilator dependent with FiO2 greater than or equal to 0.7 at 24 hours of age. Either bovine SOD (0.25 mg/kg) or saline solution was administered subcutaneously every 12 hours according to random selection until patients could be maintained in room air without ventilatory or continuous positive airway pressure (CPAP) support. SOD levels were detected in all patients given treatment. Mean peak values at 4 hours after dose ranged from 0.15 micrograms/ml (dose 1) to 0.45 micrograms/ml (dose 10). The drug was well tolerated, and no side effects were detected. Among the 31 survivors (SOD 14, placebo 17) radiologic evidence of BPD was significantly less in patients given SOD (3/14 vs 12/17, P = 0.008). Clinical signs of bronchopulmonary dysplasia (wheezing, pneumonia) were less in patients given SOD (3/14 vs 11/17, P = 0.019). Patients given SOD required fewer days of CPAP (P less than 0.003). There were no differences in days of O2 therapy, intermittent positive pressure breathing, or incidence and severity of patent ductus arteriosus or intraventricular hemorrhage. This preliminary study suggests that SOD may be helpful in reducing the severity of bronchopulmonary dysplasia in infants with respiratory distress syndrome." ]

[ "8162979", "2184993", "10599897", "15271690", "8162723", "9619472", "9493664", "9032501", "10714421", "882944", "1549826", "3353456", "11399694", "12683707", "4076354", "8980974", "10974183", "1424850", "10767227", "11192954", "6379707", "16327534", "8620707", "10665556", "7816993", "7025334" ]

[ "Quality of life in patients with chronic obstructive pulmonary disease improves after rehabilitation at home.", "Upper-limb and lower-limb exercise training in patients with chronic airflow obstruction.", "Long-term effects of a pulmonary rehabilitation programme in outpatients with chronic obstructive pulmonary disease: a randomized controlled study.", "Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease.", "The effect of comprehensive outpatient pulmonary rehabilitation on dyspnea.", "Psychological and cognitive outcomes of a randomized trial of exercise among patients with chronic obstructive pulmonary disease.", "Out-patient rehabilitation improves activities of daily living, quality of life and exercise tolerance in chronic obstructive pulmonary disease.", "The effects of a community-based pulmonary rehabilitation programme on exercise tolerance and quality of life: a randomized controlled trial.", "Rehabilitation of patients with chronic obstructive pulmonary disease. Exercise twice a week is not sufficient!", "Physical rehabilitation for the chronic bronchitic: results of a controlled trial of exercises in the home.", "Randomised controlled trial of weightlifting exercise in patients with chronic airflow limitation.", "Effects of a supervised home exercise program on patients with severe chronic obstructive pulmonary disease.", "The effectiveness of outpatient pulmonary rehabilitation in chronic lung disease: a randomized controlled trial.", "Pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.", "Physical exercise and resistive breathing training in severe chronic airways obstruction--are they effective?", "Low intensity peripheral muscle conditioning improves exercise tolerance and breathlessness in COPD.", "Short- and long-term effects of outpatient rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial.", "Inspiratory muscle training combined with general exercise reconditioning in patients with COPD.", "Long-term effects of outpatient rehabilitation of COPD: A randomized trial.", "Home-based exercise is capable of preserving hospital-based improvements in severe chronic obstructive pulmonary disease.", "Exercise training and breathing control in patients with chronic airflow limitation.", "Managing chronic obstructive pulmonary disease in the community. A randomized controlled trial of home-based pulmonary rehabilitation for elderly housebound patients.", "A comparison between an outpatient hospital-based pulmonary rehabilitation program and a home-care pulmonary rehabilitation program in patients with COPD. A follow-up of 18 months.", "Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial.", "[Value of individualized rehabilitation at the ventilatory threshold level in moderately severe chronic obstructive pulmonary disease].", "Randomised controlled trial of rehabilitation in chronic respiratory disability." ]

[ "We have developed a rehabilitation programme at home and have investigated its effects on quality of life (QOL), lung function, and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). We studied 43 patients with severe airflow obstruction: forced expiratory volume in one second (FEV1) 1.3 +/- 0.4 l (mean +/- SD), FEV1/inspiratory vital capacity (IVC) 37 +/- 7.9%. After stratification, 28 patients were randomly allocated in a home rehabilitation programme for 12 weeks. Fifteen patients in a control group received no rehabilitation. The rehabilitation group received physiotherapy by the local physiotherapist, and supervision by a nurse and a general practitioner. Quality of life was assessed by the four dimensions of the Chronic Respiratory Questionnaire (CRQ). We found a highly significant improvement in the rehabilitation group compared to the control group for the dimensions dyspnoea, emotion, and mastery. Lung function showed no changes in the rehabilitation group. The exercise tolerance improved significantly in the rehabilitation group compared to the control group. The improvement in quality of life was not correlated with the improvement in exercise tolerance. Rehabilitation of COPD patients at home may improve quality of life; this improvement is not correlated with an improvement in lung function and exercise tolerance.", "We designed a randomized controlled study to evaluate the benefit of upper-limb exercise training, alone and in combination with walking training, in patients with severe CAO. In an outpatient department supervised by a physiotherapist, we evaluated 28 patients with severe stable CAO (FEV1, 32 percent of predicted). Patients were randomly allocated to either a control (eight), upper-limb (six), lower-limb (seven), or combined (seven) exercise group. The upper-limb group trained with a circuit of upper-limb exercises, the lower-limb group by walking, and the combined group with both. Exercise was for one hour three times per week for eight weeks. Assessment before and after training included pulmonary function, mouth pressures, respiratory muscle endurance, maximal bicycle exercise test, maximal and submaximal arm ergometer, six-minute walking distance, and a scale of well-being (Bandura scale). Twenty-six patients completed the program. There was a significant improvement (Wilcoxon rank sum test) in the following: six-minute walking distance in the lower-limb (p less than 0.005) and combined (p less than 0.003) groups; arm ergometer in the upper-limb (p less than 0.005) and combined (p less than 0.04) groups; and the scale of well-being in the combined (p less than 0.005) group. There was no significant change in any other parameter measured. We conclude that exercise training improves exercise performance in severe CAO, that the training is specific for the muscle group trained, and that upper-limb exercises should be included in training programs for these patients.", "Fifty patients with severe chronic obstructive pulmonary disease (FEV1 < 50% pred.) were randomized to a rehabilitation group and a control group. The rehabilitation group took part in an individualized multidisciplinary, outpatient 12-month rehabilitation programme. Exercise training was intensive during the first 6 weeks and was then gradually replaced by an individual home-training programme and booster sessions. Controls received the usual outpatient care. Positive effects were found in terms of maximum symptom-limited exercise tolerance and walking distance (13.5 and 12.1% increase, respectively) in the rehabilitation group compared with the controls. Quality of life measurements showed minor beneficial effects on the Sickness Impact Profile, indicating a higher level of activity. No effect was seen on the St George's Respiratory Questionnaire or the Mood Adjective Check List. Patients expressed their enthusiasm for the rehabilitation programme in a study-specific questionnaire.", "Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). Men with COPD have high prevalence of low testosterone levels, which may contribute to muscle weakness. We determined effects of testosterone supplementation (100 mg of testosterone enanthate injected weekly) with or without resistance training (45 minutes three times weekly) on body composition and muscle function in 47 men with COPD (mean FEV(1) = 40% predicted) and low testosterone levels (mean = 320 ng/dl). Subjects were randomized to 10 weeks of placebo injections + no training, testosterone injections + no training, placebo injections + resistance training, or testosterone injections + resistance training. Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration (to the middle of the normal range for young men). The lean body mass (by dual-energy X-ray absorptiometry) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training (p < 0.001). Increase in one-repetition maximum leg press strength averaged 17.2% with testosterone alone, 17.4% with resistance training alone, and 26.8% with testosterone + resistance training (p < 0.001). Interventions were well tolerated with no abnormalities in safety measures. Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels.", "To evaluate the effect of outpatient pulmonary rehabilitation (OPR) on dyspnea, we measured this symptom using a visual analogue scale during graded treadmill exercise testing and with baseline and transitional dyspnea indices (TDI). The latter measure overall dyspnea in three spheres: functional impairment, magnitude of task, and magnitude of effort. Twenty patients with COPD referred for OPR were randomly assigned to either a treatment group (T, n = 10), with dyspnea evaluated at baseline then shortly following a 6-week OPR program, or a control group (C, n = 10), with dyspnea evaluated at baseline then following a 6-week waiting period. No significant change in maximal exercise performance from baseline to repeated testing was observed in either group. Dyspnea at maximum treadmill workload (Dmax), which did not significantly change in C, decreased from 74.4 +/- 18.9 percent at baseline to 50.5 +/- 23.2 percent post-OPR in T (p = 0.006). The Dmax related to minute ventilation (Dmax/VEmax) and oxygen consumption (Dmax/VO2max) also significantly decreased following OPR. The reduction in exertional dyspnea was apparent by the second minute of exercise. Additionally, TDI focal scores were significantly higher in T than C (2.3 +/- 1.06 vs 0.2 +/- 1.75 units, p = 0.006), indicating decreased overall dyspnea following OPR. These results point to significant improvements in both exertional and clinically assessed dyspnea following OPR.", "Exercise rehabilitation is recommended increasingly for patients with chronic obstructive pulmonary disease (COPD). This study examined the effect of exercise and education on 79 older adults (M age = 66.6 +/- 6.5 years; 53% female) with COPD, randomly assigned to 10 weeks of (a) exercise, education, and stress management (EXESM; n = 29); (b) education and stress management (ESM; n = 25); or (c) waiting list (WL; n = 25). EXESM included 37 sessions of exercise, 16 educational lectures, and 10 weekly stress management classes. ESM included only the 16 lectures and 10 stress management classes. Before and after the intervention, assessments were conducted of physiological functioning (pulmonary function, exercise endurance), psychological well-being (depression, anxiety, quality of life), and cognitive functioning (attention, motor speed, mental efficiency, verbal processing). Repeated measures multivariate analysis of variance indicated that EXESM participants experienced changes not observed among ESM and WL participants, including improved endurance, reduced anxiety, and improved cognitive performance (verbal fluency).", "The purpose of this study was to investigate the effects on activities of daily living, quality of life, and exercise tolerance of a comprehensive out-patient rehabilitation programme for patients with moderate-to-severe chronic obstructive pulmonary disease. In this randomized and controlled trial, the main outcome measures were Activities of Daily Living (ADL) score, York Quality of Life Questionnaire (YQLQ) score, Chronic Respiratory Disease Questionnaire (CRDQ) score, 6 min walking distance (6MWD), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). The rehabilitation programme included physical training, occupational therapy, education, and smoking cessation therapy, and lasted for 12 weeks. The patients were evaluated at entry, halfway through, and at the end of the programme. Follow-up was at 24 weeks. Forty seven patients were recruited, and 16 in each group completed the trial. There were significant differences in the improvements in ADL and CRDQ between the control and the treatment groups at 12 and 24 weeks, and at 24 weeks, respectively. At 6, 12 and 24 weeks, improvements in the 6MWD were 21.6 versus 79.8, 36.1 versus 113.1 and 21.4 versus 96.2 for control and treatment groups, respectively (p<0.004). A correlation matrix showed only ADL and 6MWD to be significantly correlated; the matrix was also used to validate the translated questionnaires. The programme required 124 staff-hours in total. An inexpensive, comprehensive out-patient rehabilitation programme can produce long-term improvement in activities of daily living, quality of life, and exercise tolerance in patients with moderate-to-severe chronic obstructive pulmonary disease.", "The present multicentre study evaluates the differences in efficacy between a 3 month rehabilitation programme including drug treatment, and a 3 month control period of drug treatment only, for asthmatic patients and patients with chronic obstructive pulmonary disease (COPD). The programme was run by physiotherapists in eight local practices, and included exercise training, patient education, breathing retraining, evacuation of mucus, relaxation techniques, and recreational activities. In a randomized controlled trial with a cross-over design, the effects of rehabilitation were evaluated 3 and 6 months after baseline measurements in terms of exercise tolerance and quality of life (QOL). Exercise tolerance was assessed using submaximal cycle ergometer tests and 6 min walking tests. QOL was evaluated by means of the Chronic Respiratory Disease Questionnaire (CRDQ). After 3 months, the patients who started with rehabilitation showed significant improvements in endurance time (421 s) and cardiac frequency (6 beats.min-1) during cycling, walking distance (39 m), and total CRDQ score (17 points) compared to the control group. These improvements were still significant after 6 months. Additional analysis indicated that the asthmatic patients and the patients with COPD responded to rehabilitation in a similar way, with the exception that there was a greater improvement in walking distance for asthmatics. Improvements in exercise tolerance were not significantly correlated with improvements in QOL. Rehabilitation of patients with asthma or chronic obstructive pulmonary disease in local physiotherapy practices improves exercise tolerance and quality of life.", "Several studies of chronic obstructive pulmonary disease (COPD) have shown that pulmonary rehabilitation, consisting of at least three training sessions a week, improves exercise performance and health status. This study investigates feasibility, effect and economic aspects of a rehabilitation programme consisting of two sessions a week for 8 weeks. Twenty-four patients with moderate COPD were randomized to rehabilitation and 21 to placebo. Patients were assigned to an 8-week programme of exercise plus education (Exercise group) or conventional community care (Placebo group). The rehabilitation program was carried out in a hospital outpatient setting and consisted of 16 h exercise and 13.5 h of education. The exercise group received physiotherapy and education twice a week. Seven patients did not complete the programme. The characteristics of the 38 COPD-patients at baseline were the following: (mean +/- SD) forced expiratory volume in 1 sec (FEV1) 1.1+/-0.4 1 (47% of predicted), 6-min walking distance (6MWD) 413+/-75 m, score of St. George's Respiratory Questionnaire (SGRQ) 44+/-21. Health-status, assessed by SGRQ and The Psychological General Well-being (PGWB) Index, did not improve. Rehabilitation resulted in an insignificant improvement in the 6MWD [29 m (95% confidence interval: -8 -66 m)]. We conclude that a rehabilitation program consisting of exercise and education twice a week for 8 weeks had no effect on exercise performance and well being in patients with moderate COPD.", "Twenty-four men with chronic bronchitis participated in a controlled trial of a physical training scheme. The training involved progressive stair-climbing exercises carried out over a three-month period unsupervised at home. The twelve men in the exercise group benefited significantly in terms of general well-being and reduced breathlessness. Their exercise tolerance increased significantly as judged by increased walking speed in a simple 12-minute walking test and by a greater work load tolerated in a progressive work load test on a bicycle ergometer. The mean stride length during the walking test increased significantly with training. No significant changes occurred in body weight, ventilatory function tests or heart rate on exercise. There were no important changes in the control group. It is not clear whether the improvements noted were due to physiological changes such as improved neuromuscular coordination producing a more efficient walking pattern or to predominantly psychological factors such as increased tolerance of dyspnoea. The study demonstrates that a simple training scheme which can be administered from a hospital clinic or family doctor's surgery is safe, feasible, and of benefit to the chronic bronchitic.", "BACKGROUND PATIENTS: with chronic airflow obstruction are often limited by muscle fatigue and weakness. As exercise rehabilitation programmes have produced modest improvements at best a study was designed to determine whether specific muscle training techniques are helpful.\n Thirty four patients with chronic airflow limitation (forced expiratory volume in one second (FEV1) 38% of predicted values) were stratified for FEV1 to vital capacity (VC) ratio less than 40% and arterial oxygen desaturation during exercise and randomised to a control or weightlifting training group. In the experimental group training was prescribed for upper and lower limb muscles as a percentage of the maximum weight that could be lifted once only. It was carried out three times a week for eight weeks.\n Three subjects dropped out of each group; results in the remaining 14 patients in each group were analysed. Adherence in the training group was 90%. In the trained subjects muscle strength and endurance time during cycling at 80% of maximum power output increased by 73% from 518 (SE69) to 898 (95) s, with control subjects showing no change (506 (86) s before training and 479 (89) s after training). No significant changes in maximum cycle ergometer exercise capacity or distance walked in six minutes were found in either group. Responses to a chronic respiratory questionnaire showed significant improvements in dyspnoea and mastery of daily living activities in the trained group.\n Weightlifting training may be successfully used in patients with chronic airflow limitation, with benefits in muscle strength, exercise endurance, and subjective responses to some of the demands of daily living.", "The purpose of this study was to analyze the effects of a home exercise program on physical work capacity and dyspnea during activities of daily living in patients with severe chronic obstructive pulmonary disease. Twenty patients with severe respiratory impairment were assigned in a stratified, random manner to an Exercise Group (n = 10) or a Control Group (n = 10). Patients in the Exercise Group performed the supervised home exercise program of daily mobility, strengthening, and endurance exercises. Patients in the Control Group were visited regularly by a physical therapist but did not follow the exercise program. Six patients were eliminated from the study, either because of death (n = 1) or noncompliance with experimental conditions (n = 5), leaving each group with seven patients. The results of a progressive bicycle ergometer test after 18 weeks showed a significant between-group difference in physical work capacity. The physical work capacity of patients in the Exercise Group had improved 3% and had deteriorated 28% for patients in the Control Group (p less than .05). The symptom-limited multistage step test and the Chronic Respiratory Disease Questionnaire showed no difference in the patients' physical work capacity or dyspnea during ADL. Although not conclusive, this study yielded some evidence for the beneficial effects of home exercise training on patients with severe chronic obstructive pulmonary disease.", "Patients with chronic pulmonary disease have been shown to benefit from pulmonary rehabilitation programs. Published work has often been from specialized teaching centers and has involved inpatient stay. We assessed an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic lung disease, using the St. George's Respiratory Questionnaire (SGRQ) (which measures health-related quality of life) as the primary outcome measure.\n We undertook a randomized, prospective, parallel-group controlled study of an outpatient rehabilitation program in 65 patients with COPD (44 men and 21 women; mean age, 69.5 years [SD, 9.2 years]; FEV(1), 41% predicted [SD, 18.5%]). The active group (n = 36) took part in a 6-week program of education (2 h weekly) and exercise (1 h weekly). The control group (n = 29) were reviewed routinely as medical outpatients. The SGRQ was administered under supervision by a blinded observer at study entry, 12 weeks, and 24 weeks.\n The SGRQ in the active group was 59.9 (SE, 2.0) at study entry (n = 36), 47.4 (SE, 2.3) at 12 weeks (n = 32), and 50.6 (SE, 2.5) at 24 weeks (n = 24). The SGRQ in the control group was 59.3 (SE, 2.5) at study entry and did not change significantly over 24 weeks. There was a difference of 10.4 points (confidence interval [CI], 3.6 to 17.3) between the two groups at 12 weeks (p < 0.001) and of 8.1 points (CI, 1.4 to 14.9) at 24 weeks (p = 0.02) in favor of the active group.\n A 6-week outpatient-based program significantly improved quality of life in patients with moderate-to-severe COPD. Benefit was still evident after 24 weeks.", "Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in India. Drug treatment alone does not optimize therapy. Pulmonary rehabilitation has been found to improve the physical efficiency of COPD patients. Therefore, we evaluated the effect of domiciliary pulmonary rehabilitation programme in patients of COPD.\n Forty patients of stable COPD having severe airflow obstruction were included in the study. They were divided into control and experimental groups randomly. Rehabilitation included walking, breathing exercises, postural drainage, controlled coughing and changes in life style activities. Exercises of 30 minutes duration were performed at home twice daily for four weeks supervision. Six-minute walking distance, forced expiratory volume in one seocond (FEV1) and various indices of chronic respiratory disease questionnaire (CRDQ) were measured in both experimental and control groups before and after completion of the study.\n In the experimental group, after four weeks, the mean (+/- SD) difference in six-minute walking distance, dyspnoea, mastery, fatigue and emotion scores were 54.2 (26.7) meters, 0.96 (0.26), 0.89 (0.44), 0.90 (0.40) and 0.91 (0.32) respectively. Changes in all these parameters were statistically significant (p < 0.001) as compared to the control group. There was no significant change in FEV1.\n It was concluded that domiciliary pulmonary rehabilitation for four weeks results in significant improvement in the quality of life and exercise tolerance, even without improvement in FEV1.", "Twenty-one patients with severe chronic irreversible airflow obstruction (FEV1 consistently less than 1.2 l) were allocated randomly to one of two training programmes designed to reduce respiratory disability or a placebo training control group. Daily structured physical exercise, twice daily inspiratory muscle training by resistive breathing, or daily placebo training were undertaken for 10 weeks, and the effects on lung function, exercise capacity, respiratory symptoms and psychological state compared. Maximal work achieved on a progressive bicycle exercise test was significantly increased in all groups (36%, 23% and 34% respectively) and global improvement in mood also occurred. There was no significant change in respiratory symptom score, static lung function tests or 12 min walking distance. Neither form of active treatment showed superiority over placebo training.", "This randomized, controlled study investigated the physiological effects of a specially designed 12 week programme of isolated conditioning of peripheral skeletal muscle groups. The programme required minimal infrastructure in order to allow continued rehabilitation at home after familiarization within hospital. Forty eight patients, aged 40-72 yrs with chronic obstructive pulmonary disease (COPD) (mean (SD) forced expiratory volume in one second (FEV1) 61 (27)% of predicted normal) were randomly allocated into training (n = 32) and control (n = 16) groups. Physiological assessments were performed before and after the 12 week study period, and included peripheral muscle endurance and strength, whole body endurance, maximal exercise capacity (maximum oxygen consumption (V'O2,max)) and lung function. The training group showed significant improvement in a variety of measures of upper and lower peripheral muscle performance, with no additional breathlessness. Whole body endurance measured by free arm treadmill walking increased by 6,372 (3,932-8,812) 3 (p < 0.001). Symptom-limited maximal V'O2 was unchanged. However, the training group showed a reduction in ventilatory equivalents for oxygen and carbon dioxide, both at peak exercise and at equivalent work rate (Wmax). In summary, low intensity isolated peripheral muscle conditioning is well-tolerated, simple and easy to perform at home. The various physiological benefits should enable patients across the range of severity of chronic obstructive pulmonary disease to improve daily functioning.", "Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease (COPD) in the short term, but their long-term effects are not known. We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD.\n One hundred patients were randomly assigned to receive either an exercise training program that included cycling, walking, and strength training (n = 50) or usual medical care (n = 50). Thirty-four patients in the training group were evaluated after 6 months (end of training), and 26 were evaluated after 18 months of follow-up. In the control group, 28 patients were evaluated at 6 months and 23 after 18 months. We measured pulmonary function, 6-minute walking distance, maximal exercise capacity, peripheral and respiratory muscle strength, and quality of life (on a 20 to 140-point scale), and estimated the cost-effectiveness of the program.\n At 6 months, the training group showed improvement in 6-minute walking distance [mean difference (training - control) of 52 m; 95% confidence interval (CI), 15 to 89 m], maximal work load (12 W; 95% CI, 6 to 19 W), maximal oxygen uptake (0.26 liters/min; 95% CI, 0.07 to 0.45 liters/min), quadriceps force (18 Nm; 95% CI, 7 to 29 Nm), inspiratory muscle force (11 cm H(2)O; 95% CI, 3 to 20 cm H(2)O), and quality of life (14 points; 95% CI, 6 to 21 points; all P <0.05). At 18 months all these differences persisted (P <0.05), except for inspiratory muscle strength. For 6-minute walking distance and quality of life, the differences between the training group and controls at 18 months exceeded the minimal clinically-important difference.\n Among patients who completed the 6-month program, outpatient training resulted in significant and clinically relevant changes in 6-minute walking distance, maximal exercise performance, peripheral and respiratory muscle strength, and quality of life. Most of these effects persisted 18 months after starting the program.", "We compared, in a controlled clinical trial, the effect of specific inspiratory muscle training combined with general exercise reconditioning, for six months, with that of general exercise reconditioning alone on inspiratory muscle strength, endurance, and exercise performance in patients with COPD. Thirty-six patients were recruited into three groups; 12 patients received specific inspiratory muscle training combined with general exercise reconditioning, 12 patients underwent general exercise reconditioning alone, and the remaining 12 patients received no training. Specific inspiratory muscle training, for six months, improved the inspiratory muscle strength and endurance in patients with COPD. This training combined with general exercise reconditioning also provided improvement in exercise tolerance, and this improvement was significantly greater than that of general exercise reconditioning alone.", "To examine the short- and long-term effects of an outpatient pulmonary rehabilitation program for COPD patients on dyspnea, exercise, health-related quality of life, and hospitalization rate.\n Secondary-care respiratory clinic in Barcelona.\n We conducted a randomized controlled trial with blinding of outcome assessment and follow-up at 3, 6, 9, 12, 18, and 24 months. Sixty patients with moderate to severe COPD (age 65 +/- 7 years; FEV(1) 35 +/- 14%) were recruited. Thirty patients randomized to rehabilitation received 3 months of outpatient breathing retraining and chest physiotherapy, 3 months of daily supervised exercise, and 6 months of weekly supervised breathing exercises. Thirty patients randomized to the control group received standard care.\n We found significant differences between groups in perception of dyspnea (p < 0.0001), in 6-min walking test distance (p < 0.0001), and in day-to-day dyspnea, fatigue, and emotional function measured by the Chronic Respiratory Questionnaire (p < 0. 01). The improvements were evident at the third month and continued with somewhat diminished magnitude in the second year of follow-up. The PR group experienced a significant (p < 0.0001) reduction in exacerbations, but not the number of hospitalizations. The number of patients needed to treat to achieve significant benefit in health-related quality of life for a 2-year period was approximately three.\n Outpatient rehabilitation programs can achieve worthwhile benefits that persist for a period of 2 years.", "We examined the feasibility of home-based walking training to maintain the benefits of a short-term exercise training in patients with severe chronic obstructive pulmonary disease (COPD). After initial recovery from an exacerbation, 46 patients were randomized into a training and a control group, and 30 patients completed the programme (mean +/- SD FEV1, 36 +/- 7% predicted). The training group performed a 10-day walking training programme in the hospital, followed by a 6-month programme of supervised walking training at home, integrated into daily activities. The control group did not have exercise training in the hospital or at home. Until 6 months after discharge, lung function, exercise performance and symptom scores were assessed. Six-minute walking distance in the training group improved from day 1 to day 10 (P<0.001) and this effect was maintained over 6 months (P<0.001). On average, daily walking distance at home was 2308 m and walking was reported on 157 days. Quality of life (QoL) scores changed significantly over 6 months (P<0.001). The control group showed no significant changes in exercise performance or QoL scores throughout the whole study period. Therefore, (i) significant improvements in exercise performance and Chronic Respiratory Disease Questionnaire (CRQ) scores could be achieved after recovery from an exacerbation and (ii) these improvements were maintained after discharge, when supported by a home-based walking training.", "nan", "Pulmonary rehabilitation is essential for managing chronic obstructive pulmonary disease (COPD). Housebound COPD patients are frequently excluded from this treatment because they are unable to access outpatient pulmonary rehabilitation programs because of the severity of their disease. This randomized controlled trial assesses the effects of a 12-week home-based pulmonary rehabilitation program for 60 housebound COPD patients older than 60 years.\n Intervention patients received an individually tailored supervised walking and arm exercise program as well as individual multidisciplinary education sessions on COPD and its management. Outcomes were assessed using the 6-minute walk test, St George's respiratory questionnaire, and Borg score of perceived breathlessness. Healthcare utilization was assessed using hospital admission rates with exacerbation of COPD and average length of stay at readmission.\n Complete data for 23 patients in each group were available for analysis. There was no significant difference between groups on baseline measures. Compared with the control group, intervention patients demonstrated a significant improvement in 6-minute walk test (P = .023), Borg score of perceived breathlessness (P = .024), St George's respiratory questionnaire total score (P = .020), and impact subscore (P = .024). At 6 months, the intervention group had a significantly shorter average length of stay at readmission to hospital with exacerbation (P = .035).\n A 12-week home-based pulmonary rehabilitation is effective in improving exercise tolerance, perception of breathlessness, and quality of life for housebound COPD patients. To manage COPD in the community more effectively, health services should focus on expanding home-based pulmonary rehabilitation.", "In this study, the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program (HRP) are compared with those of a 12-week home-care rehabilitation program (HCRP) in COPD patients. A control group received no rehabilitation therapy.\n After randomization and stratification, effects on lung function, exercise performance (4-min walking test and cycle ergometer test), dyspnea, and leg effort during exercise, and well-being were assessed in 45 COPD patients with moderate to severe airflow limitation (mean [SD] FEV1 percent predicted, 42.8 [8.4]).\n After HRP and HCRP, at 3 to 6 months after the start of the study, equal improvements were detected in exercise capacity and in Borg dyspnea and leg effort scores at similar work levels during the cycle test. However, whereas after HRP at longer term values tended to return to baseline outcome, after HCRP a further ongoing significant improvement in exercise capacity was observed, while Borg dyspnea scores remained significantly improved over 18 months. Improvements in cycle workload and dyspnea score were significantly better maintained after HCRP as compared with HRP. Lung function, arterial oxygen saturation, and heart frequency during exercise did not change. A significant improvement in well-being was maintained over 18 months in both rehabilitation groups.\n Beneficial effects are achieved both after a HRP and a HCRP in COPD patients with moderate to severe airflow limitation. Yet we recommend to initiate HCRPs as improvements are maintained longer and are even further strengthened in this setting.", "Pulmonary rehabilitation seems to be an effective intervention in patients with chronic obstructive pulmonary disease. We undertook a randomised controlled trial to assess the effect of outpatient pulmonary rehabilitation on use of health care and patients' wellbeing over 1 year.\n 200 patients with disabling chronic lung disease (the majority with chronic obstructive pulmonary disease) were randomly assigned a 6-week multidisciplinary rehabilitation programme (18 visits) or standard medical management. Use of health services was assessed from hospital and general-practice records. Analysis was by intention to treat.\n There was no difference between the rehabilitation (n=99) and control (n=101) groups in the number of patients admitted to hospital (40 vs 41) but the number of days these patients spent in hospital differed significantly (mean 10.4 [SD 9.7] vs 21.0 [20.7], p=0.022). The rehabilitation group had more primary-care consultations at the general-practitioner's premises than did the control group (8.6 [6.8] vs 7.3 [8.3], p=0.033) but fewer primary-care home visits (1.5 [2.8] vs 2.8 [4.6], p=0.037). Compared with control, the rehabilitation group also showed greater improvements in walking ability and in general and disease-specific health status.\n For patients chronically disabled by obstructive pulmonary disease, an intensive, multidisciplinary, outpatient programme of rehabilitation is an effective intervention, in the short term and the long term, that decreases use of health services.", "In order to study the efficiency of individual training programs at the ventilatory threshold level, twenty COPD patients were randomized into two groups and studied over a two-month period. At the start, during, and at the end of the study all subjects performed incremental exercise tests. The trained group (59.60 SEM +/- 2.75 years) walked four times a week at the heart rate corresponding to the metabolic level of ventilatory threshold. The other group served as controls (58.2 +/- 1.80 years). A marked increase in the symptom-limited oxygen consumption (+/- 25%) (p < 0.01), the maximal ventilation (+20%) (p < 0.01), and the ventilatory threshold (+19%) (p < 0.05) was found in the trained group. No modification was recorded in the control group. The ventilatory pattern at submaximal intensities expressed in percentage of the initial oxygen consumption showed significant differences between groups, the trained-group ventilation decreased at 50% and 75% VO2 sl (p < 0.05). The breathing frequency also decreased at 50% and 75% VO2 sl (p > 0.05). Moreover, we observed an increase in the oxygen pulse at 50% VO2 sl (p < 0.05). In conclusion, this study demonstrates that individualized training at the ventilatory threshold level increases exercise tolerance and produces better ventilatory comfort in COPD patients.", "A randomised controlled study of the effects of exercise training in 39 patients with chronic respiratory disability was performed. Exercise training began with six weeks in a rehabilitation centre and was continued at home. The original control group attended the rehabilitation centre after the controlled part of the study. The treated group experienced subjective benefit from rehabilitation. The 12-minute walking distance increased on average from 523 m to 643 m in the treatment group and from 564 m to 607 m in the control group. The treatment effect of 77 m (SE 33 m) was significant at the 5% level. Treadmill exercise performance changed little and resting lung function was unaltered after rehabilitation. The treatment group maintained most of their improvement seven months later and the original control subjects improved after their rehabilitation. The study confirms the beneficial effects of exercise training in the chronically breathless and it suggests that the 12-minute walking distance is a useful index of changes in everyday exercise tolerance." ]

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[ "Effect of a monetary incentive on response to a mail survey.", "Increasing response rates in a survey of Medicaid enrollees: the effect of a prepaid monetary incentive and mixed modes (mail and telephone).", "A randomized trial of incentives to improve response rates to a mailed women's health questionnaire.", "Timing of patient satisfaction assessment: effect on questionnaire acceptability, completeness of data, reliability and variability of scores.", "Mailed survey follow-ups--are postcard reminders more cost-effective than second questionnaires?", "Design, objectives, and lessons from a pilot 25 year follow up re-survey of survivors in the Whitehall study of London Civil Servants.", "A randomized trial of opinion leader endorsement in a survey of orthopaedic surgeons: effect on primary response rates.", "Day-of-the-week effect on doctors' response to a postal questionnaire.", "Effects on subject response of information brochures and small cash incentives in a mail-based case-control study.", "Physician response rates to a mail survey by specialty and timing of incentive.", "Scratch lottery tickets are a poor incentive to respond to mailed questionnaires.", "Response rate to mailed epidemiologic questionnaires: a population-based randomized trial of variations in design and mailing routines.", "A randomised controlled trial to assess the effectiveness of offering study results as an incentive to increase response rates to postal questionnaires [ISRCTN26118436].", "Increasing returns of physician surveys.", "Does anonymity increase response rate in postal questionnaire surveys about sensitive subjects? A randomised trial.", "Recruiting survey respondents to mailed surveys: controlled trials of incentives and prompts.", "Response rates of Victorian general practitioners to a mailed survey on miscarriage: randomised trial of a prize and two forms of introduction to the research.", "Effect of a monetary incentive on chiropractors' response rate and time to respond to a mail survey.", "A comparison of response rate and time according to the survey methods used: a randomized controlled trial.", "Recruiting patients to medical research: double blind randomised trial of \"opt-in\" versus \"opt-out\" strategies.", "The effect of cash and other financial inducements on the response rate of general practitioners in a national postal study.", "Maximising response rates in a survey of general practitioners. Lessons from a Victorian survey on sexually transmissible diseases.", "Effect on survey return rates of having a signed or unsigned postcard as the third-wave mailing.", "In a mailed physician survey, questionnaire length had a threshold effect on response rate.", "Effects of different monetary incentives on the return rate of a national mail survey of physicians.", "Response rate according to title and length of questionnaire.", "Types of advance notification in reminder letters and response rates.", "Printed signatures and response rates.", "Increasing response rates for mailed surveys of Medicaid clients and other low-income populations.", "Response rates to surveys with self-addressed, stamped envelopes versus a self-addressed label.", "Labour-saving strategies to maintain survey response rates: a randomised trial.", "Unexpected effects of a prior feedback letter and a professional layout on the response rate to a mail survey in Geneva.", "Collecting saliva samples by mail.", "Differential effectiveness of telephone prompts by medical and nonmedical staff in increasing survey response rates: a randomised trial.", "From the generic to the condition-specific?: Instrument order effects in Quality of Life Assessment.", "The cost effectiveness of including pencils and erasers with self-completion epidemiological questionnaires.", "Controlled trial of the effect of length, incentives, and follow-up techniques on response to a mailed questionnaire.", "Unexpected mailed survey response rates.", "Identifying a sample of elderly people by a postal screen.", "Some experiments with factors that might affect the response of mothers to a postal questionnaire.", "The effectiveness of an advance notice letter on the recruitment of African Americans and Whites for a mailed patient satisfaction survey.", "The effects of cash and lottery incentives on mailed surveys to physicians: a randomized trial.", "Increasing response rates to postal questionnaires: a randomised trial of variations in design.", "Dentists' response to financial incentives in a mail survey of malpractice liability experience.", "Effectiveness of monetary incentives for recruiting adolescents to an intervention trial to reduce smoking.", "Effect of handwritten, hand-stamped envelopes on response rate in a followup study of hip replacement patients.", "Enclosing a pen with a postal questionnaire can significantly increase the response rate.", "Combining conditional and unconditional recruitment incentives could facilitate telephone tracing in surveys of postpartum women.", "Response rates with different distribution methods and reward, and reproducibility of a quantitative food frequency questionnaire.", "Survey response rates to a professional association mail questionnaire.", "Impact of a postcard versus a questionnaire as a first reminder in a postal lifestyle survey.", "A randomized trial of direct mailing of fecal occult blood tests to increase colorectal cancer screening.", "Race-specific versus general stamps on African-American women's survey return rates.", "Cost effectiveness of a prize draw on response to a postal questionnaire: results of a randomised trial among orthopaedic outpatients in Edinburgh.", "Thicker paper and larger font increased response and completeness in a postal survey.", "A study of mail survey method.", "Effects of disseminating research findings on response rates in a community survey: a randomised controlled trial.", "Provision of pen along with questionnaire does not increase the response rate to a postal survey: a randomised controlled trial.", "A randomised trial of telephone versus postcard prompts to enhance response rate in a phased population-based study about community preferences.", "Response rates to a mailed survey targeting childhood cancer survivors: a comparison of conditional versus unconditional incentives.", "Primer postcard improves postal survey response rates.", "The use of a prepaid incentive to convert nonresponders on a survey of physicians.", "Improving response rates among doctors: randomised trial.", "Effects of different designs and extension of a food frequency questionnaire on response rate, completeness of data and food frequency responses.", "In a randomized study of envelope and ink color, colored ink was found to increase the response rate to a postal questionnaire.", "Survey return rates using a covering letter signed by a graduate student or faculty member.", "Eliciting survey cooperation: incentives, self-interest, and norms of cooperation.", "The impact of different response alternatives on responders' reporting of health-related behaviour in a postal survey.", "Factors impacting questionnaire response in a Dutch retrospective cohort study.", "Increasing response to mailed questionnaires by including a pencil/pen.", "The effect of a direct payment or a lottery on questionnaire response rates: a randomised controlled trial.", "A randomised controlled trial to determine the effect on response of including a lottery incentive in health surveys [ISRCTN32203485].", "Effect on survey response rate of hand written versus printed signature on a covering letter: randomised controlled trial [ISRCTN67566265].", "Cross validation of some psychometric properties of the CSQ and its differential return rate as a function of token financial incentive.", "Improving return rates for health-care outcome.", "Telephone reminders are a cost effective way to improve responses in postal health surveys.", "Initial nonresponders had an increased response rate after repeated questionnaire mailings.", "Randomized trial of use of a monetary incentive and a reminder card to increase the response rate to a mailed health survey.", "The effects of variations in mode of delivery and monetary incentive on physicians' responses to a mailed survey assessing STD practice patterns.", "The effects of lottery incentive and length of questionnaire on health survey response rates: a randomized study.", "The effect of two mailing strategies on the response to a survey of physicians.", "Response to mail surveys: effect of a request to explain refusal to participate. The ARIC Study Investigators.", "A useless raffle.", "Incentives increased return rates but did not influence partial nonresponse or treatment outcome in a randomized trial.", "Possible factors affecting response to postal questionnaires: findings from a study of general practitioner services.", "The end-of-study patient survey: methods influencing response rate in the AVID Trial.", "Print format and sender recognition were related to survey completion rate.", "Effect of a newspaper article on the response to a postal questionnaire.", "Does questionnaire structure influence response in postal surveys?", "Do sexual health questions alter the public's response to lifestyle questionnaires?", "Effect of timing on the response to postal questionnaires concerning satisfaction with anaesthesia care.", "Maximizing response rates to a survey of dentists: a randomized trial.", "Does requesting sensitive information on postal questionnaires have an impact on response rates? A randomised controlled trial in the south west of England.", "Properties of the Picker Patient Experience questionnaire in a randomized controlled trial of long versus short form survey instruments.", "Effects of characteristics of the survey instrument on response rates to a mail survey of community hospitals.", "No difference in response rate to a mailed survey among prostate cancer survivors using conditional versus unconditional incentives.", "A randomized trial of the impact of certified mail on response rate to a physician survey, and a cost-effectiveness analysis.", "The effect on response rates of offering a small incentive with a mailed questionnaire.", "Effectiveness of various mailing strategies among nonrespondents in a prospective cohort study.", "Questionnaire color and response rates to mailed surveys. A randomized trial and a meta-analysis.", "The use of monetary incentives in a community survey: impact on response rates, data quality, and cost.", "Randomized trial of financial incentives and delivery methods for improving response to a mailed questionnaire.", "Effect of mailed reminders on the response rate in surveys among patients in general practice.", "Do income questions and seeking consent to link medical records reduce survey response rates? A randomised controlled trial among older people.", "[Response rates and non-response bias in a health-related mailed survey].", "Recruiting blacks to the Adventist health study: Do follow-up phone calls increase response rates?", "Improving the assessment of (in)patients' satisfaction with hospital care.", "A mail survey of United States hematologists and oncologists: a comparison of business reply versus stamped return envelopes.", "Comparison of responses to a US 2 dollar bill versus a chance to win 250 US dollars in a mail survey of emergency physicians.", "Screening optometric patients by questionnaire: methods of improving response.", "Short report: encouraging GPs to complete postal questionnaires--one big prize or many small prizes? A randomized controlled trial.", "An informational versus monetary incentive in increasing physicians' response rates.", "Questionnaire order significantly increased response to a postal survey sent to primary care physicians.", "Obtaining DNA from a geographically dispersed cohort of current and former smokers: use of mail-based mouthwash collection and monetary incentives.", "Response rates and representativeness: a lottery incentive improves physician survey return rates.", "Does it pay to pay? A randomized trial of prepaid financial incentives and lottery incentives in surveys of nonphysician healthcare professionals.", "[Mail questionnaires. A useful strategy for the follow-up of patients with a cerebrovascular stroke?].", "The effect of a monetary incentive on return of a postal health and development questionnaire: a randomised trial [ISRCTN53994660].", "Survey return rates as a function of priority versus first-class mailing.", "Physician participation in research surveys. A randomized study of inducements to return mailed research questionnaires.", "Timing payments to subjects of mail surveys: cost-effectiveness and bias.", "Effects of mailing strategies on response rate, response time, and cost in a questionnaire study among nurses.", "Improving response rates through incentive and follow-up: the effect on a survey of physicians' knowledge of genetics.", "Longer response scales improved the acceptability and performance of the Nottingham Health Profile.", "A comparison of response rate, data quality, and cost in the collection of data on sexual history and personal behaviors. Mail survey approaches and in-person interview.", "Prepayment was superior to postpayment cash incentives in a randomized postal survey among physicians.", "Using a diary to record near misses and minor injuries--which method of administration is best?", "Comparison of open and closed questionnaire formats in obtaining demographic information from Canadian general internists.", "Chance of free dinner increases response to mail questionnaire.", "Increasing response rates in physicians' mail surveys: an experimental study.", "[Evaluation of inpatient satisfaction. Comparison of different survey methods].", "Randomized trial of 5 dollars versus 10 dollars monetary incentives, envelope size, and candy to increase physician response rates to mailed questionnaires.", "The effect of conducting a lottery on questionnaire response rates: a randomised controlled trial.", "No increase in response rate by adding a web response option to a postal population survey: a randomized trial.", "Do postage stamps versus pre-paid envelopes increase responses to patient mail surveys? A randomised controlled trial.", "Selected questionnaire size and color combinations were significantly related to mailed survey response rates.", "Do postage-stamps increase response rates to postal surveys? A randomized controlled trial.", "Increasing response to a postal survey of sedentary patients - a randomised controlled trial [ISRCTN45665423].", "Improving the measurement of quality of life in older people: the York SF-12.", "A monetary incentive increases postal survey response rates for pharmacists.", "Effect of prize draw incentive on the response rate to a postal survey of obstetricians and gynaecologists: a randomised controlled trial. [ISRCTN32823119].", "Conducting physician mail surveys on a limited budget. A randomized trial comparing $2 bill versus $5 bill incentives.", "Use of a coded postcard to maintain anonymity in a highly sensitive mail survey: cost, response rates, and bias.", "Will donations to their learned college increase surgeons' participation in surveys? A randomized trial.", "Does a deadline improve men's participation in self-administered health surveys? A randomized controlled trial in general practice.", "What can you ask about? The effect on response to a postal screen of asking about two potentially sensitive questions.", "Is shorter always better? Relative importance of questionnaire length and cognitive ease on response rates and data quality for two dietary questionnaires.", "Effects of incentive size and timing on response rates to a follow-up wave of a longitudinal mailed survey.", "A randomized trial of the impact of telephone and recorded delivery reminders on the response rate to research questionnaires.", "Does sponsorship matter in patient satisfaction surveys? A randomized trial.", "Increasing the response rate to a mailed questionnaire by including more stamps on the return envelope: a cotwin control study.", "Effect of paper quality on the response rate to a postal survey: a randomised controlled trial. ISRCTN 32032031." ]

[ "We assessed the effect of a $1 incentive on response to a two-page questionnaire which was sent to 8356 female cosmetologists between 22 and 36 years old. The study population was randomly assigned to one of three groups in which a $1 incentive was enclosed with either the first or second mailing, or with none of the mailings. Ten percent of questionnaires were returned by the postal service because of an incorrect address or death of the addressee and were omitted from response calculations. Of the remaining questionnaires, 79% were completed and returned after up to three mailings. The cumulative response was highest among cosmetologists who received a $1 incentive with the first mailing, (81%; 95% confidence interval (CI), 80 to 82), intermediate among those who received $1 with the second mailing (78%, 95% CI, 77 to 79), and lowest among cosmetologists who received no incentive (74%; 95% CI, 70 to 78). Characteristics of cosmetologists who responded after having received a \"41 incentive were similar to those who responded without having received an incentive. The higher costs per response incurred by the use of an incentive must be weighed against the benefit of higher response.", "We sought to evaluate the effect of pairing a mixed-mode mail and telephone methodology with a prepaid US 2.00 dollars cash incentive on response rates in a survey of Medicaid enrollees stratified by race and ethnicity.\n Sampling was conducted in 2 stages. The first stage consisted of a simple random sample (SRS) of Medicaid enrollees. In the second stage, American Indian, African American, Latino, Hmong, and Somali enrollees were randomly sampled. A total of 8412 enrollees were assigned randomly to receive a mail survey with no incentive or a US 2.00 dollars bill.\n The response rate within the SRS after the mail portion was 54% in the incentive group and 45% in the nonincentive group. Response rates increased considerably with telephone follow-ups. The incentive SRS response rate increased to 69%, and the nonincentive response rate increased to 64%. Differences between incentive conditions are more pronounced after the first mailing (P < 0.01); almost all differences remained significant (P < 0.05) after the completion of the mail mode. The inclusion of the US 2.00 dollars incentive had similar effects on response rates and cost across the different racial and ethnic strata, except for Latino enrollees.\n A mixed-mode mail and telephone methodology is effective for increasing response rates in a Medicaid population overall and within different racial and ethnic groupings. The effectiveness of this strategy can be enhanced, in terms of response rate and cost, by including a US 2.00 dollars prepaid incentive.", "Mailed questionnaires can be a convenient method for collecting data on women's health, although poor response rates are a concern.\n As part of a survey of women's health conducted in Maryland in 2001, a randomized trial was performed to assess the effects of two incentives (US dollars 1.00 or a lottery ticket) as well as precontact with an introductory postcard on response rates. Questionnaires were mailed to 3000 women aged 40-60 who were randomized to one of six incentive/precontact groups: lottery/postcard, money/postcard, postcard only, lottery only, money only, or no incentive/no postcard.\n The overall response rate was 37.6%. Each incentive/precontact group yielded a higher response rate than the no incentive/no postcard group, although only the response rates for the lottery/postcard group (41.3%) and the money only group (40.0%) were significantly higher than that of the no incentive/no postcard group (33.1%). Money was the only factor that had a significant independent effect on likelihood of response (hazards ratio [HR] compared to no incentive = 1.22, 95% confidence interval [CI] = 1.03, 1.43). Response rates were lower in minority ZIP codes, although the effects of the incentives were generally greater than in the nonminority ZIP codes.\n These results indicate that response rates to mailed women's health questionnaires may be improved with modest incentives, particularly cash incentives.", "The present study compared the performance of a multidimensional patient satisfaction questionnaire according to the timing of questionnaire administration. Comparisons were made in terms of: (a) the completeness and representativeness of the data set (number of missing questionnaires, number missing item responses, respondents' representativeness to the target population); (b) the questionnaire acceptability to respondents (time and difficulty to complete); (c) the questionnaire reliability; and (d) variability of scores. One hundred and ten consecutive breast cancer patients hospitalised for surgery were randomised between being sent the comprehensive assessment of satisfaction with care (CASC) at 2 weeks (T(2W)) or at 3 months (T(3M)) after hospital discharge. The time to complete the CASC was shorter at T(3M) than at T(2W) and the mean percentage of item omission was lower at T(3M) (1.68) than at T(2W) (3.82). However, the response rate was much higher at T(2W) (87%) than at T(3M) (66%), making item omission non-significant. At both times of questionnaire administration samples were equally biased towards patients having undergone a less invasive surgery. Moreover, the multi-item scales of the CASC demonstrated adequate internal consistency coefficients, except the general satisfaction scale at T(3M), and fairly symmetrical distribution of scores. Response rate should be considered in priority. This criteria favoured an administration of the CASC shortly after discharge. Besides in a cancer patient population care experience and perception may vary in a 6 weeks time lapse. The timing of assessment needs to be clearly specified in cancer patients satisfaction survey.", "Finding cost-effective ways to increase response to mailed surveys is a concern for many nurse researchers. This study compared two follow-up methods: sending a second questionnaire packet versus sending a reminder postcard to those who did not respond to an initial mailing. Although the second questionnaire yielded a higher response than did the postcard, the cost per additional response was approximately 2 1/2 times higher for the questionnaire than for the postcard when the differential cost of the two mailings is considered.", "To assess the feasibility of conducting a re-survey of men who are resident in the United Kingdom 25 years after enrollment in the Whitehall study of London Civil Servants.\n A random sample of 401 study survivors resident in three health authority areas was selected for this pilot study. They were mailed a request to complete a self administered questionnaire, and then asked to attend their general practice to have their blood pressure, weight, and height measured and a blood sample collected into a supplied vacutainer, and mailed to a central laboratory. Using a 2 x 2 factorial design, the impact of including additional questions on income and of an informant questionnaire on cognitive function was assessed.\n Accurate addresses were obtained from the health authorities for 96% of the sample. Questionnaires were received from 73% and blood samples from 61% of the sample. Questions on income had no adverse effect on the response rate, but inclusion of the informant questionnaire did. Between 1970 and 1995 there were substantial changes within men in the mean blood pressure and blood total cholesterol recorded, as reflected by correlation coefficients between 1970 and 1995 values of 0.26, and 0.30 for systolic and diastolic blood pressure and 0.38 for total cholesterol.\n This pilot study demonstrated the feasibility of conducting a re-survey using postal questionnaires and mailed whole blood samples. The magnitude of change in blood pressure and blood total cholesterol concentrations within individuals was greater than anticipated, suggesting that such remeasurements may be required at different intervals in prospective studies to help interpret risks associations properly. These issues will be considered in a re-survey of the remaining survivors of the Whitehall study.", "Opinion leaders have been shown to have significant influence on the practice of health professionals and patient outcomes.\n Using focus groups, key informants, and sampling to redundancy techniques, we developed a questionnaire of surgeons' preferences in the treatment of tibial shaft fractures. Twenty-two well-respected and widely known orthopaedic traumatologists endorsed the questionnaire. We randomized 395 surgeon members of the Orthopaedic Trauma Association to receive either a questionnaire that included a letter informing them of the opinion leaders' endorsement, or a questionnaire without the endorsement.\n Surgeons who received the letter of endorsement had a significantly lower response rate at 2, 4, and 8 weeks. The absolute difference in response rates was 7.8% (4.6% versus 12.4%, P < 0.05) at 2 weeks, 13.1% at 4 weeks (28.6% versus 41.7% P < 0.02), and 12.3% at 8 weeks (47.5% versus 59.8% P = 0.02).\n The addition of a letter listing expert surgeons who endorse the survey lead to significantly lower primary response rates. Those interested in influencing physician responses cannot always assume a positive effect from endorsement by opinion leaders", "To test a possible day-of-the-week effect on doctors' response rate to a postal questionnaire.\n Dispatch of postal questionnaire randomized to Thursday or Saturday.\n A nationwide survey on doctors' attitudes.\n 200 general practitioners and 260 practising specialists/consultants.\n Response rate and Kaplan-Meier survival curve for no-response.\n The probability of response was not influenced by receiving the questionnaire just before or just after a week-end.\n Response rates in postal surveys sent to doctors cannot be improved by their receiving the questionnaire just before a week-end.", "To investigate the impact on subject response of an information brochure and cash incentives included with mailed questionnaires in case-control studies.\n A randomized trial was carried out within a case-control study investigating cancer in the Province of Ontario. Brochures were included with half of the mailed questionnaires sent to 7487 cases and 2561 controls. Controls were also sent cash incentives of $2, $5, or no money.\n With the brochure, response changed from 75.0% to 75.8% in cases, and from 70.3% to 71.1% in controls. Adjusting for differences in age, residence, sex, and cancer site/status, the change was 0.2% [95% confidence interval (CI) = -1.7-2.1] in cases, and 0.6% (95% CI = -3.1-4.3) in controls. The $2 and $5 incentives increased overall response in controls from 61.9% to 72.8% and 77.2%, respectively, i.e., by 10.9% (95% CI = 6.1-15.6) and 15.1% (95% CI = 10.4-19.7), after adjustment. This effect was largely confined to urban areas (for $2 and $5, respectively: 5.5% and 14.2% in Toronto, 15.3% and 20.4% in other urban areas vs. 2.7% and 1.0% in rural areas; p = 0.02). Response time showed little or no improvement when the brochure was included, but was markedly reduced for both the $2 and $5 incentives.\n Cash incentives can improve subject response in epidemiologic studies, whereas information brochures do not appear to have an effect.", "Historically, achieving a high response rate on physician surveys has been a challenging task. Given such concerns, understanding research strategies that facilitate adequate response rates is important. Primary care physician responses to a mail survey on smoking cessation are summarized by physician specialty and timing of incentive.\n A stratified random-sample design, stratified by patient populations-adults, adolescents, and pregnant women-was used. The sampling frame included New Jersey internists, general practitioners, family physicians, pediatricians, and obstetrician-gynecologists. A total of 2100 physicians, 700 physicians from each patient strata, were sampled and mailed a smoking-cessation survey in summer 2002. The sample was randomized by incentive timing: Half received the incentive (i.e., 25 dollars gift card) with the first survey mailing, and half received the incentive on receipt of their completed survey.\n The promised-incentive group achieved a significantly lower response rate (56%) compared with the up-front-incentive group (71.5%). Response rates by medical specialty varied overall and within incentive groups. The difference between the incentive groups was greatest among obstetrician-gynecologists (i.e., 20.2 percentage points) and was least among pediatricians (i.e., 5.8 percentage points).\n Physician response rates to mail surveys are greatly improved, especially among certain medical specialties, by using up-front incentives.", "It has been demonstrated that the enclosure of money with a mailed questionnaire increases the response rate significantly. We evaluated scratch lottery tickets as an alternative to cash.\n 1500 randomly selected Norwegians between the ages of 40 and 65 years were sent a short questionnaire. 250 received one lottery scratch ticket worth 20 Norwegian kroner (approximately 3 USD) together with the questionnaire, 250 received two scratch tickets, and 250 were promised two scratch tickets if they replied within one week. A fourth group of 250 persons received a 50 kroner banknote with the questionnaire. The remaining 500 letters served as controls.\n The overall response rate after 6 weeks was 77%. Logistic regression analysis showed that only the 50 kroner group had a response rate that was statistically significantly higher than the controls (p < 0.0001). It was also significantly higher than that in any of the other incentive groups (p < 0.0001, p < 0.004 and p < 0.0001 respectively). Female sex (p < 0.001) and age (p < 0.002) increased the response rate significantly.\n It is possible that the recipients scratched their cards before completing the questionnaire, and that it was a disincentive for the majority that they did not win anything. Lottery scratch tickets are no substitute for cash as an incentive to respond to a questionnaire.", "Although self-administered questionnaires are major sources of information in epidemiology, comparatively little has been done to study practical aspects of design and mailing. The objective of this study was to evaluate various measures taken to increase the response rate. A questionnaire was mailed in July 1995 to a random sample (n = 2,000) of the Swedish population aged 20-79 years. Using a randomized factorial study design, the questionnaire and mailing procedures were changed in three ways: preliminary notification, length of the questionnaire, and mention of telephone contact. The overall questionnaire retrieval rate was 49%. Preliminary notification (adjusted odds ratio of receiving a completed questionnaire = 1.30, 95% confidence interval (CI) 1.08-1.56 relative to the absence of preliminary notification) and short length of the questionnaire (odds ratio = 1.24, 95% CI 1.04-1.48 relative to a long questionnaire) were both independently associated with a higher retrieval rate. Of eight possible combinations, the one comprising preliminary notification, a short questionnaire, and no mention of telephone contact gave the highest retrieval rate, 56%. The lowest retrieval rate, 40%, was observed for the combination of no preliminary notification, a long questionnaire, and mention of telephone contact. Young age, male sex, and urban residence significantly lowered the retrieval rate. Although there was a positive association between the questionnaire retrieval rate and partial nonresponse (missing answers in retrieved questionnaires), the marginal losses due to the latter did not cancel the gains by optimized mailing routines. Old age was the strongest determinant of partial nonresponse. The data provide evidence that design and mailing strategies, as well as demographic characteristics, may greatly influence the response rate of mailed epidemiologic questionnaires.", "Postal questionnaires are widely used to collect outcome data on participants. However, a poor response to questionnaires will reduce the statistical power of the study and may introduce bias. A meta analysis of ten trials offering study results, largely in the fields of education and marketing, was shown to be ineffective, with the odds ratio for response with offering research findings is 0.92 (95% CI 0.75 to 1.11). However uncertainty still exists as it is uncertain whether results from such trials can be extrapolated to that of a health care setting. The aim of this study was to assess whether offering participants study results increases the response rates to postal questionnaires.\n 1038 women aged over 70 years were remotely randomised by computer in a 3:1 ratio. 250 participants did not receive the offer of knowing the results of the trial and 788 participants were offered the results of the trial in a postal questionnaire. The main outcome measure was response rate. Chi square test was used to evaluate the overall differences in response rate between the two groups. An adjusted analysis, adjusting for whether the participant was taking calcium and age was also undertaken.\n The response rates were not significantly different Odds Ratio 0.88 (95% confidence intervals 0.48 to 1.63) p = 0.69.\n Offering study results to women living in the community aged over 70 does not increase response rates to postal questionnaires. Although researchers have an ethical obligation to offer participants study results, since 10% of women did not wish to receive the results, investigators should give participants the option to opt out of receiving the study's results.", "nan", "The aim of the study was to determine whether complete anonymity improves the response rates to a postal questionnaire.\n The study derived from a series of postal surveys on AIDS knowledge conducted on six different dates in 1986 and 1987. The sample was randomly divided into two, each group being sent the same questionnaire. One group was informed that the replies were anonymous, the other that they were not. The latter were sent reminders.\n Recipients of the questionnaires were drawn from the Southampton electoral rolls.\n 300 people in each survey (total 1800) were sent questionnaires, representing on each occasion a different 1:500 systematic sample.\n Response rate was 49% for the anonymous questionnaires and 51% for the numbered questionnaires. Reminders boosted the response in the numbered group to 72%.\n There is no evidence that anonymity improves response to postal questionnaires, but the use of reminders may do so.", "Three controlled experiments tested the efficacy of 1) a postcard or telephone prompt, 2) a lottery, 3) monetary incentives, and 4) questionnaire length to recruit adult survey respondents to a random sample of residences in San Diego, California, during 1986-1988. In experiment 1, the group randomly assigned to receive a telephone call prenotification plus the lottery incentive responded 26-66% more frequently than did controls (p = 0.02) after a single mailing. The postcard plus lottery was 17-54% more effective than no intervention with controls (p = 0.05). A second mailing of the survey weakened these effects. In experiment 2, the group randomly assigned to receive a two-page survey with the lottery announcement responded 69% more frequently after one mailing (p = 0.03) and 53% more frequently after a second mailing (p = 0.04) than the group that received an eight-page survey without the lottery incentive. The shorter form alone or the lottery alone did not increase response rates significantly relative to the long form without a lottery. In experiment 3, a monetary incentive of $5.00 contingent on response to the second mailing of the survey increased the rate of response from initial \"nonresponders\" by 100% relative to control who received no incentive (p = 0.03) and 75% over those who received $1.00 not contingent on response (p = 0.04). Little sampling bias and no reactivity was attributable to the recruitment procedures.", "To identify whether the form of introduction to a study and knowledge of a substantial prize influence the response rate of general practitioners (GPs) to a postal survey.\n A postal survey of 700 randomly selected Victorian GPs concerning management of early pregnancy bleeding and miscarriage, incorporating two randomised-controlled trials of recruitment methods; analysis of response rates and costs at 4 weeks and 11 weeks.\n The response rate was 61.5% of eligible participants. Doctors made aware of a prize were more likely to respond in the first four weeks (difference in response rate 10.2%, 95% confidence interval (CI) 2.8%-17.6%). This difference diminished after the first four weeks. Doctors introduced to the survey by a telephone call were no more likely to respond than those introduced by a postcard. The use of a postcard saved 73% of the cost of introducing the survey by telephone. Female doctors were more likely than males to reply (difference 12.3%, 95% CI 4.7%-19.9%). Rural doctors were no more likely to reply than urban doctors. Very few doctors (16.2%) completed a Practice Assessment activity associated with the survey.\n A valuable prize will accelerate response to a survey by GPs, thereby reducing the costs of follow-up. The cost of telephoned introductions is not justified, when compared with a brief written introduction.", "nan", "The purpose of this study was to evaluate the effects of recorded and standard deliveries, and stamped and franked return envelops in a postal survey of Korean-Vietnam veterans. Nine hundred veterans were randomly divided into four subgroups. A randomized controlled trial was conducted for two mailing strategies. The 52 study subjects to whom mail was undeliverable and 36 additional study subjects found not to be residing at the listed addresses were excluded from the study. The 699 (86%) surveys were returned within 39 business days after the first mailing. The response rate for the recorded delivery (88%) was significantly higher than that of the standard delivery (82%)(p = 0.03), and the response rate of the stamped return envelops (88%) was higher than that of the franked return envelops (85%)(p = 0.27). The replies for the recorded and standard deliveries arrived an average of 10.2 and 9.9 business days, respectively, after the first mailing (p = 0.60). The average times of the responses for the stamped and franked return envelops were 9.8 and 10.4 business days, respectively (p = 0.25). Recorded deliveries significantly increased the response rate compared to standard deliveries, and stamped return envelops slightly increased the response rate a little compared to franked return envelops. The timing of response of recorded deliveries was similar to that of standard deliveries but the volume of response of recorded deliveries was higher than that of standard deliveries.", "To evaluate the effect of opt-in compared with opt-out recruitment strategies on response rate and selection bias.\n Double blind randomised controlled trial.\n Two general practices in England.\n 510 patients with angina.\n Patients were randomly allocated to an opt-in (asked to actively signal willingness to participate in research) or opt-out (contacted repeatedly unless they signalled unwillingness to participate) approach for recruitment to an observational prognostic study of patients with angina.\n Recruitment rate and clinical characteristics of patients.\n The recruitment rate, defined by clinic attendance, was 38% (96/252) in the opt-in arm and 50% (128/258) in the opt-out arm (P = 0.014). Once an appointment had been made, non-attendance at the clinic was similar (20% opt-in arm v 17% opt-out arm; P = 0.86). Patients in the opt-in arm had fewer risk factors (44% v 60%; P = 0.053), less treatment for angina (69% v 82%; P = 0.010), and less functional impairment (9% v 20%; P = 0.023) than patients in the opt-out arm.\n The opt-in approach to participant recruitment, increasingly required by ethics committees, resulted in lower response rates and a biased sample. We propose that the opt-out approach should be the default recruitment strategy for studies with low risk to participants.", "Low response rates are acknowledged as a potential source of bias in survey results. Response rates are a particular problem in surveys of GPs. Thus, the methods used to encourage response to mailed surveys and the influence of inducements in maximizing response rates are fundamental issues to be examined when addressing the problem of response bias.\n To increase the overall response rate to a national study of GPs and to explore the effects of financial and non-financial inducements on response rates.\n Two mailing waves of a postal questionnaire to a 20% random sample of all GPs in England and Wales had achieved a 33% response rate. For the third mailing wave, the non-responding GPs were then divided into a control group, a group who were offered a donation to charity to complete the questionnaire and a group who were offered cash. The charity and cash groups were further subdivided into 5 pounds and 10 pounds groups to assess the effect of the size of the inducement offered. For the control group, a fourth wave was sent the offer of a 5 pounds or 10 pounds incentive.\n Response was positively affected by the offer of an inducement. Cash, however, had a more substantial effect than the offer of a donation to charity. Older GPs were less likely to participate overall, whereas male GPs were more likely to respond to a cash inducement. Doctors who had seen more patients were less likely to reply earlier and were more likely to respond to the offer of cash.\n Primary care is going through many changes, some of which have increased the workload of the GP. It may now be that, to achieve the response rates needed to validate policy-related research, the offer of inducements will become a necessary part of the research process.", "To describe factors that influence participation by general practitioners (GPs) in survey research, and in particular to examine the effectiveness of telephone prompts made by a GP researcher compared with non-medical researchers in a survey of GPs on sexually transmissible diseases (STDs).\n A questionnaire survey of knowledge, attitudes, behaviour and practice (KABP) in relation to STDs was distributed to 520 Victorian GPs randomly selected from the Australian Medical Publishing Company's (AMPCo) database of Australian medical practitioners.\n Number of GPs able to be contacted by telephone and cumulative and overall response rates to the questionnaire.\n The overall response rate was 85%. Although the GP researcher was able to make contact by telephone in a higher proportion of cases (80%) than the non-GP researchers combined (69%, p < 0.01) response rates were not significantly different (83% versus 87%).\n Telephone prompts to encourage GP response in survey research need not be made by a medical practitioner. Other important factors in relation to response rate that should be considered by researchers are GP involvement in the developing and piloting of the survey instrument, incentives and provision of detailed feedback of the results of the survey.", "This study assessed differences in response rates to a three-wave mail survey when signed or unsigned postcards were the third wave of the mailing (after two mailings of the questionnaire). A total of 259 signed postcards and 259 unsigned postcards were mailed as the third-wave mailing. There were 34 signed postcards and 30 unsigned postcards returned, a not significantly different distribution by chi-square test.", "To examine the association between questionnaire length and response rate in a mailed survey of generalist physicians randomly selected from the American Medical Association master file.\n In a pilot study, otherwise similar questionnaires of 30 different lengths (849 to 1,867 words) were mailed to 192 physicians in April 1999. In the main study, questionnaires of 16 different lengths (564 to 988 words) were mailed to 1,700 physicians between June 1999 and January 2000.\n In the pilot study, response rate decreased from 60% for questionnaires 849 words in length to 16.7% for questionnaires over 1,800 words in length. Logistic regression revealed an odds ratio of 0.887 (95%CI 0.813, 0.968; p=0.006) for word count, expressed in units of 100 words. In the main study, response rate varied between 51.5% and 71.4%. Logistic regression showed no association between response and word count (OR 0.988; 95%CI 0.896, 1.090; p=0.81).\n There appears to have been a threshold in these studies of approximately 1,000 words. Questionnaires above the threshold had lower response rates than those below it (38.0% vs. 59.4%).", "Mail surveys of physicians have been characterized by lower response rates than general population surveys, raising concerns about nonresponse bias. Although monetary incentives have routinely been used to improve survey response among physicians, questions remain regarding how much of an incentive is most cost-effective. The present study seeks to further examine the effects of incentive size on response rates to a national mail survey of physicians.\n This study used a random sample of 873 physicians practicing in the United States; the response rate was 65% (n = 563). Respondents were randomly assigned to receive a $5, $10, or $20 cash incentive in the initial mailing. Except for the magnitude of the incentive, the procedures for each condition were identical, with each respondent receiving up to 3 follow-up mailings and 2 telephone calls.\n Overall response rates ranged from 60.3% for the $5 incentive category to 68.0% for the $10 incentive category. Differences in overall response rates across the incentive categories, however, were not significant. Higher levels of incentives also did not significantly reduce the number of mail and/or telephone interventions required to reach the target response rate of 60.0%. As expected, aggregate costs (excluding labor) were lowest for the $5 incentive group.\n Our findings suggest that changes in the magnitude of incentive do not automatically result in increases in survey response among physicians. Possible reasons for this lack of effect as well as alternatives to monetary incentives are addressed.", "The purpose of this study was to investigate how response rates to a postal questionnaire are affected by title and length of the survey instrument. Five questionnaires, which differed according to title and length, were designed. Each questionnaire was mailed to a random sample of one thousand Norwegian women aged, 35-49 years. A total of 3,106 questionnaires were returned (62.1%). The highest response rate (70.2%) was achieved by a two-page questionnaire entitled \"Women and Cancer\". An otherwise identical questionnaire entitled \"Oral Contraceptives and Cancer\" had a response rate of 60.7%. Questionnaires entitled \"Women and Cancer\" with a length of four and six pages had a response rate of 62.8% and 63.3%, respectively. The four page questionnaire entitled \"Women, Lifestyle and Health\" had the lowest response rate of 57.1%. This study shows that in a general population of Norwegian women the title of a postal questionnaire influences the response rate. The results indicate that although the shortest questionnaire had the highest response rate, the most extensive survey instrument did not have the lowest response rate. The distribution of risk factors for breast cancer did not vary according to response rate or design of questionnaire. The overall findings of this study suggest that the benefits from the increased information obtained from extensive postal questionnaires out-weighs a potential non-response bias due to a somewhat lower response rate.", "nan", "nan", "Mailing surveys to low-income populations is often avoided because of concern about low response rates. In this study, the authors used a mailed survey of a low-income population to test whether $1.00 or $2.00 cash-response incentives were worth the expense and whether 2-day priority mail ($2.90 postage) would yield a sufficiently higher response rate than certified mail ($1.52 postage) to justify its cost. In 1994, 2,243 randomly selected families in subsidized health care programs in Pierce County, Washington, were randomly sent no incentive, $1.00, or $2.00 in the first of three mailings. For the third mailing, nonrespondents were randomly assigned to receive either certified or 2-day priority mail. After 4 weeks, the response rates were 36.7%, 48.1%, and 50.3% for the no-incentive, $1.00, and $2.00 groups, respectively. After three mailings, the cost per response was the lowest for the group that received $1.00. The response rate for the certified mailing (28.1%) was significantly higher than the rate for the more expensive priority mailing (21.7%). No incentive-related bias was detected. The authors concluded that the most efficient protocol for this low-income population was to use a $1.00 incentive in the first mailing and a certified third mailing.", "Return rates were studied for a survey on the perceived professional preparation of therapeutic recreation specialists by directors of college and university recreational therapy programs. Specifically, returns for surveys with self-addressed, stamped return envelopes enclosed were compared to those with self-adhering return address labels. Of the 75 surveys sent with a self-addressed, stamped return envelope, 42 responses (56%) were returned at a cost of $2.58 per respondent. Of the 72 surveys sent with a self-adhering return address label 43 responses (59.7%) were returned at a cost of $1.56 per response. While there was no significant difference in return rates, the self-adhering return address label was more cost effective than the self-addressed, stamped, return envelopes.", "To evaluate response-aiding strategies feasible in large surveys, we randomly allocated general practitioners (GPs) to one of four intervention groups: Group 1 received 'exhaustive' telephone prompts by a medical peer in advance of a questionnaire; Group 2, inclusion of an embossed pen with the questionnaire; Group 3, an advance letter prompt; and Group 4, a 'single attempt' advance telephone prompt by a non-medical research assistant. Follow-up procedures were identical. Response rates by group were not significantly different overall (chi 2 = 4.59, df = 3, p = 0.20) although advance prompts by a medical peer were significantly more effective than other strategies for male GPs. The difference in overall response rates between males (63%) and females (74%) was significant (chi 2 = 15.40, df = 1, p < 0.01). No other response bias was evident. Our demonstration of a significant interaction between respondent sex and response-aiding strategy invites further research.", "nan", "Collecting saliva samples by mail can serve numerous purposes in epidemiologic research. The objectives of this study were to assess what proportion of participants in a mail survey would provide a saliva sample and whether incentives could improve participation. In 1995, 2,994 students, faculty, and staff members of Geneva University, Geneva, Switzerland, were randomized to receive, together with a mailed questionnaire about smoking, a saliva vial, a ballpoint pen, the offer of a lottery, or any combination of these. After one mailing and a reminder letter, response rates were 52% among those who had been requested to provide saliva and 63% among controls (p < 0.001). In the former group, most respondents (98%) provided a saliva sample. Incentives improved participation only among those who were asked to provide saliva (lottery: +11% response, p = 0.003; pen: +6% response, p = 0.1). The final participation, after up to three reminders, was 76% overall. The authors conclude that while the collection of saliva samples by mail is feasible it tends to decrease response rates.", "We conducted a randomised trial to determine the differential effectiveness of a telephone prompt by a medical researcher compared with a nonmedical research assistant in improving response rates of general practitioners to a survey and to compare personnel costs. A national random sample of Australian general practitioners was allocated randomly to two intervention groups. In advance of a self-administered questionnaire, Group A (n = 184) received a telephone prompt by a medical researcher and Group B (n = 189) a prompt by an experienced nonmedical research assistant. Other aspects of survey administration were identical for both groups. The five-month cumulative response rate obtained by the medical researcher (81 per cent) was not significantly different from that of 72 percent obtained by the research assistant (chi 2 = 3.3, 1 df, P = 0.07). For Group A, 279 telephone calls, consuming 23 hours 15 minutes, were made. Group B required more calls (384) and more time (32 hours). Using the relevant award pay scales, the estimated personnel costs for each group were $631 and $601 respectively. We conclude that an experienced nonmedical research assistant is as effective as a medical practitioner in administering telephone prompts to enhance survey response rates, although savings are not necessarily made.", "Generic and condition-specific measures of quality of life are often used in parallel. Despite extensive evidence of question ordering effects in the general survey literature, there is no consensus on which type of measure should be administered first and little previous conclusive research into instrument ordering effects.\n To investigate the effects of instrument ordering on response rates, speed of response, and response patterns to questions on health-related quality of life.\n Subjects were randomized to two different versions of a self-completion questionnaire; in the first, condition-specific measures of quality of life preceded generic instruments; in the second version, the relative positions were reversed.\n Adults with asthma or angina from 62 family practices in northeast England.\n Instruments were the generic Medical Outcomes Study Short Form 36-item questionnaire, the EQ-5D, the Newcastle Asthma Symptoms Questionnaire, the Asthma Quality of Life Questionnaire, and the Seattle Angina Questionnaire. Effects were assessed in terms of questionnaire response rates, speed of response, item nonresponse rates, internal consistency, and domain scores on the quality of life measures.\n Instrument ordering had no effect on questionnaire response rates or response speed. Only condition affected item nonresponse rates. Some ordering effects in respect of quality of life scores were observed, but these were inconsistent within and between conditions, and none of the differences were clinically significant.\n There is little effect of instrument ordering on responses to self-completed measures of quality of life. Further research is required to test whether this finding extends to other methods of administration.", "It is cheap to process epidemiological data from optical mark read (OMR) questionnaires. Respondents should use a pencil to complete OMR questionnaires, but many will not unless these are supplied. Sending pencils and erasers is expensive. Does sending pencils and erasers increase the response rate as cost-effectively as sending reminders, or does this decrease the error rate and offset data checking costs? We mailed 300 smokers and half were randomised to receive pencils and erasers. The relative risk (95% confidence intervals) for the response rate for the pencil group relative to the non-pencil group was 0.77 (0.46-1.29) and for the error rate was 1.31 (0.78-2.21). Sending pencils and erasers was not cost-effective in sensitivity analysis with any response rate or using the confidence intervals. Including pencils with mailed epidemiological questionnaires probably has no benefit and any plausible benefit does not offset the costs of sending pencils and erasers.", "Mailed questionnaires are an economical method of data collection for epidemiologic studies, but response tends to be lower than for telephone or personal interviews. As part of a follow-up study of volunteers who provided a brief health history and blood sample for a blood specimen bank in 1989, the authors conducted a controlled trial of the effect of length, incentives, and follow-up techniques on response to a mailed questionnaire. Interventions tested included variations on length of the questionnaire, effect of a monetary incentive, and effect of a postcard reminder versus a letter accompanied by a second questionnaire. Response was similar for the short (16-item, 4-page) and long (76-item, 16-page) questionnaire groups. The non-monetary [corrected] incentive did not improve the frequency of response. The second mailing of a questionnaire was significantly better than a postcard reminder in improving responses (23% vs. 10%). It is important to systematically test marketing principles to determine which techniques are effective in increasing response to mailed questionnaires for epidemiologic studies.", "nan", "This paper describes how a sample of elderly people were identified from the electoral register using an initial postal screen, and reports a technique that was used to increase the response to the screen.", "The effects of a number of controllable factors on the response rate of mothers to a postal questionnaire were assessed by a series of experiments. In one a factorial design was used to look at seven factors with a random sample of 1600 mothers. The main findings were that the responses to questionnaires of 8, 16 or 24 pages were similar, but that rather more mothers replied when the questionnaires contained only factual questions than when they covered both facts and attitudes. Another experiment, based on a similar sample, compared the response rates when the questionnaires were sent out by a government organization or by the Institute for Social Studies in Medical Care, and found no difference. The final experiment looked at the effect of precoding the answers or asking respondents to tick boxes beside their replies and again found no difference in response rates. The overall response rate was 79 per cent, but this varied between 66 and 87 per cent in the ten randomly selected study areas--a much greater variation than that found with any of the experimental factors.", "Evaluate an advance notice letter for enhancing patient satisfaction survey response rates in African Americans and Whites.\n Randomized trial of an advance notice letter (versus no letter) mailed two weeks prior to a mail satisfaction survey in a random sample of 600 African American and White patients ages 50 and older, stratified by ethnicity, sex, and age.\n The advance letter was independently associated with a completed survey in Whites (odds ratio = 2.73; 95% confidence interval [CI] 1.66, 4.50), but not in African Americans (odds ratio = 1.24; 95% CI 0.76, 2.02). Being male was independently associated with returning a survey in Whites (odds ratio = 1.86; 95% CI 1.13, 3.06). Younger age (odds ratio = 0.98; 95% CI 0.96, 0.99) was independently associated with a completed survey in African Americans.\n An advance letter prior to a satisfaction survey is associated with increased response rates in Whites, but not in African Americans.", "Low response rates, especially among physicians, are a common problem in mailed survey research. We conducted a randomized trial to examine the effects of cash and lottery incentives on response rates. A total of 4,850 subjects were randomized to one of three interventions accompanying a mailed survey-no incentive (n = 1,700), cash payment [three levels of Hong Kong dollars (HKD) $10, $20, and $40; N = 50 in each subgroup], or entry into a lottery (three levels of HKD$1,000, $2,000, and $4,000; N = 1,000 in each subgroup) on receipt of the completed questionnaire. The response rates were higher among those offered incentives than those without (19.8% vs. 16.8%, P =.012). Cash was the more effective incentive compared to lottery (27.3% vs. 19.4%, P =.017). Response also increased substantially between the first and second mailings (14.2% vs. 18.8%, P >.001). In addition, those with specialist qualifications were more willing to participate in mailed surveys. We found no significant differences in response outcomes among the various incentive arms. Cash reward at the $20 level was the most cost-effective intervention, in terms of cost per responder. Further systematic examination of the effects of different incentive strategies in epidemiologic studies should be encouraged.", "Low response rates to postal questionnaires can threaten the validity of studies by reducing the effective sample size and introducing bias. The identification of methods with which to optimise response rates could, therefore, improve the quality of studies. In an attempt to identify such methods, we undertook a randomised trial of two simple variations in questionnaire design.\n Using a 2 x 2 factorial design, we conducted a randomised trial to test two variations in questionnaire design; the questionnaires were printed on either single-sided or double-sided paper and had either a single- or multiple-booklet layout. Using equal random allocation, 3836 women were randomised to receive one of these questionnaires as part of a study investigating risk factors for osteoporotic fractures.\n One thousand eight hundred and seventy questionnaires were returned, giving an overall response rate of 48.7%. There were no significant differences in the overall response to each of the four questionnaire designs. When the number of responders who completed at least 50% of each of the three sections was identified, it was found that single-booklet questionnaires had a better response than the multiple-booklet questionnaires and that single-sided questionnaires had a better response than double-sided questionnaires. However, these results were not significant at the 5% level. There were no significant differences in the response to questions on the odd (left-hand side) pages for the single- compared with the double-sided questionnaires.\n As the most cost-effective use of resources, we would advocate the use of double- rather than single-sided questionnaires, and use of a single- rather than multiple-booklet design.", "This two-part methodologic research was designed to evaluate the effects of a financial incentive on questionnaire response rate and response bias for general dentists surveyed by mail. Subjects were 517 clinicians randomly selected from a two-state population of practitioners insured by a single malpractice liability carrier. Subjects received a check for either $5 or $10 in the original mailing. In Study 1, a single mailing and postcard follow-up resulted in a 57.8 percent (111/192) response rate. In Study 2, employing Dillman's Total Design Method, a 69.6 percent (208/299) response was obtained after a third mailing. Analysis of response rate by incentive level in each study revealed no significant differences. In contrast, early responders (first mailing and follow-up postcard) differed from late responders (second and third mailings) on age (41.4 vs 37.0 years; T = 2.17; P = .032), non-Caucasians (27.7% vs 63.9%; chi 2 = 17.3; df = 4; P < .002), females (13.9% vs 27.8%; chi 2 = 3.9; df = 1; P < .05), foreign-trained (7.0% vs 19.4%; chi 2 = 16.5; df = 2; P < .001), and dissatisfaction with practice (31% vs 51%; chi 2 = 7.8; df = 4; P = .10). Thus, the magnitude of the financial incentive in this experiment had no differential effect on response rate. But differences in responses from late responders (proxies for nonresponders) on demographic characteristics and key study variables suggest the persistence of response bias despite an acceptable response rate. Future dental health survey research should employ tests for response bias on both sets of variables.", "The study objective is to evaluate the effect of monetary incentives on response rates of adolescents to a smoking-related survey as the first step toward participation in an intervention trial.\n A sample of 4,200 adolescent members of a managed care organization were randomized to one of four incentive groups: a $2 cash group, a $15 cash group, a $200 prize drawing group, or a no-incentive group. We compared group-specific response rates and willingness to be contacted about future study activities, as well as costs.\n Incentives increased survey response rates (55% response without incentive vs. a 69% response with incentive), with response of 74% in the $15 cash group, 69% in the token group, and 63% with a prize incentive. Incentives did not adversely affect willingness of adolescents to be contacted about a smoking intervention, (65% willing with incentives vs. 60% without, P = 0.03). In terms of cost per additional survey completed, token and prize groups were marginally more expensive than the no-incentive group ($0.40 and $1.42, respectively) while the large cash incentive was substantially more costly ($11.37).\n Monetary incentives improve response rates to a mailed survey, without adverse impact on willingness to further participate in intervention activities. However, a variety of issues must be considered when using incentives for recruitment to intervention studies.\n Copyright 2000 American Health Foundation and Academic Press.", "nan", "It is important to maximize response rates to postal questionnaires. We compared the impact of three low-cost interventions on response rates.\n A 2 x 2 x 2 factorial trial was conducted, nested within TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears). Three interventions were evaluated: (1) enclosing a TOMBOLA-branded pen with the questionnaire (as opposed to no pen); (2) sending the questionnaires by first class post (as opposed to second class); and (3) enclosing a preaddressed return envelope on which there was a second class postage stamp (rather than a freepost business-reply envelope). Nine hundred thirty women, aged 20-59 years, due to receive a TOMBOLA psychosocial questionnaire by post during June-August 2003 were randomized.\n Enclosing a pen resulted in a statistically significant 7.0% increase in the cumulative proportion of questionnaires returned (from 61.5 to 68.5%; P = .002). The adjusted odds of response was significantly raised (odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.04-1.82). Neither first class post nor providing a stamped envelope had a significant impact on response. There were no interactions between the interventions.\n Enclosing a pen with a questionnaire can significantly increase response. This low-cost strategy was effective against a background of \"good practice\" with regard to the administration of postal questionnaires.", "To compare tracing and contact rates using alternative incentives in a computer-assisted telephone interview (CATI) survey among postpartum women.\n In a randomized trial of 1,061 postpartum women 18-49 years of age selected from four Iowa counties, we compared the effects of: (1) unconditional $5 telephone card incentive enclosed with the introductory letter followed by $25 incentive conditional upon successful telephone tracing, contact, and completion of CATI (Group 1, n = 530) vs. (2) $30 incentive conditional upon subject completion of CATI (Group 2, n = 531).\n Overall telephone tracing and contact rates achieved were 67.8% and 66.6%, respectively. Tracing (70.2 vs. 65.4%, P = .09) and contact (68.5 vs. 64.8%, P = .26) rates were consistently higher among subjects assigned the combination of a conditional and an unconditional incentive. The combined incentive type had a greater impact on telephone tracing success rates for subjects on whom we could not initially locate an active telephone number (16.7 vs. 7.3%, P = .07) when compared to subjects for whom we found an active telephone number at the time of mailing the introductory letter (78.9 vs. 75.9%, P = .30).\n Combining conditional and unconditional recruitment incentives can facilitate telephone tracing efforts in surveys conducted among recently postpartum women.", "To evaluate the use of a self-administered quantitative food frequency questionnaire (QFFQ) in a national dietary survey concerning (a) response rates with different distribution methods and reward; (b) degree of underreporting of energy intake; (c) reproducibility of the QFFQ; and (d) seasonal variation on reported intake.\n A pilot study was performed in 1992 to test response rates to the QFFQ with three different distribution methods, with and without reward, in a random sample of 1200 adults aged 16-79 y. In another study, the QFFQ was distributed to a nation-wide, representative random sample of 5008 adults aged 16-79 y during June, September, November 1993 and March 1994. Reproducibility was evaluated among 90 responders to the survey who answered another QFFQ six weeks later.\n The distribution method combining postal distribution and collecting the QFFQ by interviewer as well as an offer to participate in a lottery, gave the highest response rate (72%). The possibility to get a reward increased the response rate by 9, 14 and 57%, respectively, depending on the distribution method used. The mean daily energy intake and the percentage of subjects claiming to have unlikely low energy intake did not differ significantly between the different ways of distribution. In the main survey the mean ratio between energy intake and estimated basal metabolic rate was 1.58 among men and 1.47 among women, and 37% of men and 45% of women had a ratio below 1.35. Spearman rank correlations between the two QFFQ ranged from 0.48 (edible fats) to 0.91 (coffee) with a median coefficient of 0.70. For nutrients correlations ranged from 0.55 (carbohydrate E%) to 0.81 (alcohol), with a median coefficient of 0.72. The season of questionnaire administration was of minor importance for the reported intake of the main foods and nutrients.\n The QFFQ-method is suitable for use in a Norwegian nutritional surveillance system.\n National Nutrition Council, Ministry for Agriculture, Ministry for Health and Social Affairs and Norwegian Research Council.", "The purpose of this research was to study the effect of various direct mail techniques on professional nurses' response rates to questionnaires. A random sample of 700 registered professional nurses consisting of five groups who were members of New York State Nurses Association (NYSNA) were mailed a questionnaire with 22 items. The study demonstrated that the response rates were directly attributable to techniques used. Providing information about the association was related to significantly decreased response rates and monetary incentives with significantly increased response rates. A combined direct mailing for questionnaire completion and membership solicitation was not effective for either purpose.", "The study aimed to consider the impact of two different types of reminder on response rates and costs in a postal survey.\n The study was a cross sectional survey. A self-completion lifestyle questionnaire was used. Those who did not respond after the initial mailing were randomly allocated to receive either a postcard or questionnaire as a first reminder. All outstanding non-responders received a questionnaire as a second reminder.\n A representative sample of 698 adults aged 16-70 was used, drawn from a family health services authority register.\n Postcard reminders were as effective as questionnaire reminders in increasing response whether one or two reminders are sent. The costs per response were calculated. Two questionnaires as reminders were found to be 1.7 times more expensive than a postcard plus questionnaire. Including the initial mailing, the cost per response using all questionnaires was 1.3 times the cost when a postcard was used for the first reminder.\n To increase the response to a postal survey effectively and economically, two reminders should be sent--first a postcard and then a questionnaire.", "Although colorectal cancer screening by using a fecal occult blood test (FOBT), flexible sigmoidoscopy, colonoscopy, or barium enema x-ray reduces the incidence of and death from colorectal cancer, the rate of colorectal cancer screening in the general population is low. We conducted a randomized trial consisting of direct mailing of FOBT kits to increase colorectal cancer screening among residents of Wright County, Minnesota, a community in which colorectal cancer screening was promoted.\n At baseline, we mailed a questionnaire about colorectal cancer screening to a random sample of Wright County residents aged 50 years or older who were randomly selected from the Minnesota State Driver's License and Identification Card database (estimated N = 1451). The sample was randomly allocated into three equal subgroups: one group (control) received only the questionnaire, one group received FOBT kits by direct mail with reminders, and one group received FOBT kits by direct mail without reminders. Study participants were sent a follow-up questionnaire 1 year after baseline. We used the responses to the questionnaires to estimate the 1-year change in self-reported screening rates in each group and the differences in the changes among the groups, along with the associated bootstrap 95% confidence intervals (CIs).\n At baseline, the estimated response rate was 86.5%, self-reported adherence to FOBT guidelines was 21.5%, and overall adherence to any colorectal cancer screening test guidelines was 55.8%. The 1-year rate changes in absolute percentage for self-reported adherence to FOBT use were 1.5% (95% CI = -2.9% to 5.9%) for the control group, 16.9% (95% CI = 11.5% to 22.3%) for the direct-mail-FOBT-with-no-reminders group, and 23.2% (95% CI = 17.2% to 29.3%) for the direct-mail-FOBT-with-reminders group. The 1-year rate changes for self-reported adherence to any colorectal cancer screening test were 7.8% (95% CI = 3.2% to 12.0%) for the control group, 13.2% (95% CI = 8.4% to 18.2%) for the direct-mail-FOBT-with-no-reminders group, and 14.1% (95% CI = 9.1% to 19.1%) for the direct-mail-FOBT-with-reminders group.\n Direct mailing of FOBT kits combined with follow-up reminders promotes more rapid increases in the use of FOBT and nearly doubles the increase in overall rate of adherence to colorectal cancer screening guidelines in a general population compared with a community-wide screening promotion and awareness campaign.", "This study examined cancer survey return rates in relation to race-specific versus general stamps used on self-addressed stamped return envelopes. Of the 104 race-specific stamps sent 41 (39%) were returned. Of the 108 general stamps sent 41 (38%) were returned. Thus, race-specific stamps were not effective in increasing return rates in this sample of African-American women.", "nan", "To investigate the effect of font size and paper thickness on the response to, and completion of, a self-completion postal questionnaire among older people with joint pain.\n Randomized trial. People aged 50 years and older with joint pain who consulted a general practitioner at one of five general practices in Central Cheshire were sent a postal questionnaire. Questionnaire format (large or small font size, thick or thin paper) was randomly allocated using a 2 x 2 factorial design.\n Questionnaires were received from 502 out of 650 participants (crude response 77%). Response was significantly higher for participants receiving questionnaires with a larger font size (79.3% vs. 75.2%; hazard ratio 1.26, 95% confidence interval: 1.02, 1.56). Paper thickness had no significant effect on response. Completion (measure by assessing double-page turnover error) was increased in participants receiving questionnaires printed on thicker paper (3.2% vs. 7.1%; P=0.049) but was not affected by font size.\n This study demonstrates that questionnaires in larger font and on thicker paper may produce higher and more complete responses than surveys using standard size font and standard thickness paper, and should therefore be considered in studies among older people.", "A major disadvantage of the mail survey in medical research is non-response, which may introduce bias. This study measured the effect of two simple factors on the response rate to a questionnaire concerning headache and migraine in a survey of 2,508 electors. The two factors were the class of postage and the colour of envelopes used; neither was found to have a significant effect. It was concluded that cheaper mailing methods are not likely to jeopardise response.", "nan", "nan", "nan", "Mailed surveys are widely used to collect epidemiologic and health service data. Given that nonresponse can threaten the validity of surveys, modest incentives are often used to increase response rates. A study was undertaken among childhood cancer survivors and their parents to determine if response rate to a mailed survey differed with provision of immediate versus delayed incentives.\n A self-administered survey designed to ascertain health behaviors was mailed to 397 childhood cancer survivors (and their parents if the survivor was <18 years of age). Subjects were randomized into two groups based on gender, age, race, and cancer type. One group received a 10 US dollars incentive with their blank survey (unconditional incentive), whereas the other group received the incentive upon receipt of their completed survey (conditional incentive). If children were minors, both the parent and the child received incentives.\n No significant differences in response rates were observed with respect to gender, age, race, or cancer type. However, significant differences in response rates were observed between incentive groups, with unconditional incentives yielding significantly higher response rates than conditional incentives for child survivors who were > or =18 years (64.4% versus 49.0%), as well as younger child survivors (62.5% versus 43.6%) and their parents (64.8% versus 41.5%; all P < 0.05).\n The provision of an immediate incentive generated significantly higher response rates to this mailed health survey among childhood cancer survivors and their parents. Given that survey studies are commonly conducted across various pediatric populations, these findings may help inform the design of future pediatric survey research.", "This study measures the effect of an intervention to improve mailed survey response rates.\n A randomised controlled trial of a 'primer' postcard was performed as part of a large survey in Victoria in 1997. Prior to the survey mailout, half the sample of 800 general practitioners supplied by the Health Insurance Commission was sent, at random, a primer card to request prompt return of the survey.\n The intervention resulted in a more rapid return of the survey and improved overall response rates from 60% to 66%. The increased cost per returned survey (40 cents) was largely offset by fewer non-responders requiring follow-up.\n A primer postcard is a time and cost-efficient method to increase response rates in general practitioner surveys.\n Public health researchers should consider implementing this intervention to improve response rates to postal surveys. Reports of other response maximising strategies should report the cost per returned survey to allow better comparison.", "nan", "nan", "The authors studied how the introduction of several modifications to a basic food frequency questionnaire can influence the results of dietary surveys. Modifications covered eight combinations based on three levels: increasing versus decreasing order of frequency categories; questionnaires without versus with questions about portion sizes, and questionnaires without versus with extra non-dietary questions. The sample included 6783 women between the ages of 40 and 70 years who took part in mammography screening. The women were randomly assigned to one of the eight study groups. All of the women in each group received one of the eight differently modified questionnaires. The forms extended in length by extra non-dietary questions and portion size categories resulted in a 20% higher total non-response compared to the shorter basic form. Partial non-response was significantly lower for all four questionnaire types that included portion sizes. When portion sizes were included in the questionnaire, the reported mean frequency of consumption was significantly reduced for fat (-10 times per month), milk (-6), bread (-5), vegetables (-2) and fish (-0.4). The decreasing order of responses to the frequency categories was associated with a statistically significant increase in the frequency responses for bread (2.6 times per month), vegetables (2) and fish (0.6). These data provide evidence that the design and extension of food frequency questionnaires influence the results of dietary studies.", "To assess the effect of the colors of the envelope and ink on the response rate to a postal questionnaire in a study screening for undiagnosed parkinsonism in people aged 65 years and over in the community.\n A total of 2,524 people aged 65 years and over from five general practices in Aberdeen were randomized to receive a questionnaire about the symptoms of parkinsonism printed in either colored (green) or black ink, and sent out in either a brown or white envelope.\n The overall response rate was 63.5%. There was no significant interaction between envelope and ink color. The use of green ink compared to black significantly increased the response rate from 61.4% to 65.7% (OR 1.20, 95% confidence interval 1.02, 1.41). There was no overall effect of envelope color on response rate (62.3% brown and 64.8% white, OR 0.90, 95% confidence interval 0.76, 1.06) but there was significant heterogeneity between the general practices. When this general practice-envelope interaction was accounted for, brown envelopes had a significantly lower response rate than white ones (OR 0.49).\n This study, along with existing evidence, has shown that the use of certain ink colors in postal questionnaires is likely to increase response rates relative to black ink. The effect of envelope color was inconsistent both within this study and between previous studies.", "This study assessed differences in response rate when the author of a survey was identified as a graduate student or a faculty member. A survey on research ethics was mailed to 500 nurse faculty members with half of the covering letters signed as a graduate student and half signed as a faculty member. There were 388 (78%) out of a possible 495 surveys returned. The response rate was 78% for graduate student and 77% for faculty identifications, not significant by chi-square test.", "Given the weaker ties to community as noted by scholars such as Robert Putnam, survey researchers should not be surprised by a decline in survey participation over the past 10 years. This research analyzes the use of incentives coupled with introductory themes emphasizing cooperation and helpfulness--cooperative norms in American society--to understand their effects on survey response. This article analyzes two separate experiments (one phone and one mail) that provide evidence that norms of cooperation matter in the decision to participate in a survey, suggesting that this is particularly true at the refusal conversion stage. These results indicate that survey researchers may use such themes to their advantage, especially when conducting a nonresponse follow-up in a mail survey.", "Previous experimental research in other topic areas has shown that the choice of response alternatives can influence respondents' reporting of the frequency of vaguely defined events and that the set of response alternatives is treated as information in the interpretation of the question. The aim of this study was to examine whether such affects would occur in the context of respondents reporting of health-related events using high and medium frequency closed format response categories, which might be used interchangeably by researchers. The study consisted of a postal survey of n = 518 patients aged > or = 18 years randomly selected from the patient list of a diabetes centre and who were equally and randomly allocated to one of three conditions (Condition A: high frequency response alternatives/horizontal orientation; condition B: medium frequency response alternatives/horizontal orientations; condition C: high frequency response alternatives/vertical orientation). Testing for the effect of response alternatives for the combined responses of five vaguely defined questions between conditions A and B was chi 2 = 5.5, p = 0.019, for the difference in proportions, indicating that overall, those respondents presented with response alternatives discriminating at medium frequency, reported significantly fewer target events than those presented with high frequency response alternatives. Testing for the effect of orientation of the combined question responses between conditions A and C, differences in proportions between conditions, did not reach statistical significance (p > 0.05). Findings from this and previous studies indicate that response alternatives provide information on the interpretation of vaguely defined questionnaire items and that their choice should not be left to intuition alone when designing questionnaire items.", "To study questionnaire length, type of consent, approach to recruitment, and subject characteristics on participation in epidemiologic studies.\n As part of a health survey among Dutch subjects treated for ear, nose, and throat disorders in childhood, we conducted a pilot study of 200 individuals who were randomly assigned to one of four categories, defined by length of questionnaire (long vs. short) and type of consent form (basic vs. multi-option). In addition, among 8402 subjects eligible to be in the main study (average age 41 years in 1997), we examined the effect of approach to recruitment and subject characteristics on participation rates.\n The pilot study showed a non-significant 10% increase in participation rate using the shorter questionnaire, but no differences by type of consent form. In the full survey, the participation rate was 49% after the first mailing. Response increased by 15% after a written reminder and by 10% after a telephone survey. The total participation rate was 74%. Attained age, sex, exposure status, age at exposure, and response to an earlier survey were determinants of participation rates. Among male non-participants, outright refusal was less frequent than non-response. The refusal rate, unlike the non-response rate, was positively associated with older age at time of survey.\n Health survey participation is influenced by questionnaire length, frequency of contact, and subject characteristics.", "Nonmonetary incentives lead to small increases in response rates to mailed questionnaires. However, inclusion of a pen or pencil, which may be a facilitating factor as well as a reward, has not been shown to improve response to health surveys in prior trials. In 2001 and 2002, the authors conducted two US trials in which a study-logo pen or pencil was randomly included in a second questionnaire mailed to nonresponders to a first mailing. In the first study, of 10,686 nonresponders to a cohort recruitment mailing, response to the second mailing was 55% with inclusion of a pen versus 40% without one (p < 0.001). In the second study, of 141 nonresponders to a pilot follow-up survey conducted 2 years after entry into a cohort, response was 43% with inclusion of a pencil versus 24% without one (p = 0.02). This 15-19 percentage point increase for mailing 2 translated to a 5-6 percentage point increase after the two mailings combined. In a simulated study of three mailings based on these studies, the overall response rate increased by 4 percentage points at no added cost through inclusion of a pencil in the second mailing. The additional cost of the pencil was compensated for by the reduced number of nonrespondents sent packets at the third mailing. This study supports including a study-logo pen or pencil in a second questionnaire mailing to nonrespondents as a cost-effective method of increasing response rates.", "nan", "Postal questionnaires are an economical and simple method of data collection for research purposes but are subject to non-response bias. Several studies have explored the effect of monetary and non-monetary incentives on response. Recent meta-analyses conclude that financial incentives are an effective way of increasing response rates. However, large surveys rarely have the resources to reward individual participants. Three previous papers report on the effectiveness of lottery incentives with contradictory results. This study aimed to determine the effect of including a lottery-style incentive on response rates to a postal health survey.\n Randomised controlled trial. Setting: North and West Birmingham. 8,645 patients aged 18 or over randomly selected from registers of eight general practices (family physician practices). Intervention: Inclusion of a flyer and letter with a health questionnaire informing patients that returned questionnaires would be entered into a lottery-style draw for pound 100 of gift vouchers. Control: Health questionnaire accompanied only by standard letter of explanation. Main outcome measures: Response rate and completion rate to questionnaire.\n 5,209 individuals responded with identical rates in both groups (62.1%). Practice, patient age, sex and Townsend score (a postcode based deprivation measure) were identified as predictive of response, with higher response related to older age, being female and living in an area with a lower Townsend score (less deprived).\n This RCT, using a large community based sample, found that the offer of entry into a lottery style draw for pound 100 of High Street vouchers has no effect on response rates to a postal health questionnaire.", "It is important that response rates to postal surveys are as high as possible to ensure that the results are representative and to maximise statistical power. Previous research has suggested that any personalisation of approach helps to improve the response rate. This experiment tested whether personalising questionnaires by hand signing the covering letter improved the response rate compared with a non-personalised group where the investigator's signature on the covering letter was scanned into the document and printed.\n Randomised controlled trial. Questionnaires about surgical techniques of caesarean section were mailed to 3,799 Members and Fellows of the Royal College of Obstetricians and Gynaecologists resident in the UK. Individuals were randomly allocated to receive a covering letter with either a computer printed signature or a hand written signature. Two reminders were sent to non-respondents. The outcome measures were the proportion of questionnaires returned and their time to return.\n The response rate was 79.1% (1506/1905) in the hand-signed group and 78.4% (1484/1894) in the scanned and printed signature group. There was no detectable difference between the groups in response rate or time taken to respond.\n No advantage was detected to hand signing the covering letter accompanying a postal questionnaire to health professionals.", "The Consumer Satisfaction Questionnaire (CSQ) was developed by Larsen, Atkisson, Hargreaves, and Nguyen (1979) and has been mentioned as a possible \"standard scale\" for the evaluation of consumer satisfaction with mental health treatment because of its unidimensionality, reliability, validity and ease of use. A mail survey of ex-clients who had terminated treatment during the preceding year from one of six offices of a regional mental health center in the Rocky Mountain area strongly cross-validated these characteristics as well as other results from the consumer satisfaction literature. In addition, based upon evidence from marketing research, a randomly selected half of the ex-clients surveyed was offered a token inducement of two cents for returning the questionnaire while the other half was not. A significantly greater proportion of ex-clients who received the token inducement returned their questionnaires than did those who had not. This approach appears to be promising and further research with it is indicated.", "The objective was to test two methods of reducing loss of data in follow-up by abbreviating the questionnaire and offering a token monetary incentive. Primary data were collected between September 14, 1998 and July 23, 1999 from an adult psychiatric population, representing about 50% of all patients, all of whom agreed to participate in a quality-assurance monitoring program. Briefer components of the SF-36 Health Status Survey were expected to yield higher return rates than would the SF-36 plus a form assessing amount of treatment received. Small monetary incentives were expected to result in higher return rates also. Patients were randomly assigned to the groups (n = 73 each). Abbreviation of the questionnaire and use of a monetary incentive each reduced attrition by 10%. A diminishing returns effect for both methods was observed. Further study of a possible interaction between the questionnaire's length and monetary incentive is recommended.", "To assess the effectiveness of a telephone reminder in increasing responses to postal surveys and to calculate the differential costs per completed questionnaire.\n Randomised controlled trial.\n Australian university and rehabilitation medicine practice.\n The trial was conducted in 1999 among the 143 non-respondents to a questionnaire about work related neck and upper body disorders. The questionnaire was sent to two Australian female samples: 200 office workers (Sample A) and 92 former rehabilitation medicine patients (Sample B). A reminder letter, another copy of the questionnaire and a final letter were sent at two week intervals. Half of the non-respondents within each sample were randomly selected to receive a telephone reminder just after the second mailout of the questionnaire. All direct costs were calculated.\n Responses were significantly higher among those who received the telephone reminder intervention (relative risk 2.54, 95% confidence intervals 1.43 to 4.52). Analysed by intention to phone, 47% of non-respondents in Sample A and 38% in Sample B returned a complete questionnaire after the intervention, compared with 21% and 10%, respectively, in the control groups. For the 112 women (combined samples) who returned completed questionnaires before randomisation, the average cost per respondent was AUD14. There was a higher total cost for the intervention groups (AUD851 versus AUD386 for controls), but the significantly higher number of additional completed responses (31 versus 12) resulted in a 15% lower marginal cost per completed questionnaire in those groups.\n Telephone reminders are cost effective in improving responses to postal surveys.", "There is a growing evidence base on methods to improve response rates in surveys among patients. This study aimed to determine the additional effect of two intensive follow-up procedures compared to a simple follow-up procedure.\n Randomized controlled trial that compared repeated mailing of the questionnaire and a request to explain nonparticipation with a simple reminder card. The study population comprised 955 elderly adults registered with 26 general practitioners in The Netherlands.\n A total of 530 adults (56%) returned the questionnaire within 3 weeks and a total of 640 (67%) after follow-up. Repeated mailing of the questionnaire had additional effect compared to the simple reminder card in the group of initial nonresponders (relative risk=1.60, 95% confidence interval: 1.11-2.31), but not regarding the overall response rate. A request to explain nonparticipation did not have additional effect.\n Repeated mailing of the questionnaire increased the effectiveness of follow-up among initial nonresponders.", "Insufficient response rates are a frequent problem in mailed epidemiologic health surveys. As part of a health survey of 1,235 young adults conducted from November 1992 through January 1993 in Geneva, Switzerland, a randomized factorial trial was carried out to assess the contributions of two tactics to increase response rates. The first incentive was the promise of sending 10 Swiss francs (7 US dollars) to respondents; the second was a red postcard, mailed 2 days after the questionnaire, which reminded potential participants to complete the questionnaire. The most effective strategy according to interim analysis was to be selected for follow-up mailings. Two weeks after the first mailing, response rates were 65% for those who had received both incentives, 57% for those who had been offered the money reward only, 54% for recipients of the reminder card, and 48% for those who had received neither incentive (p based on chi 2 (3 df) test < 0.001). The relative hazards of responding were 1.34 (95% confidence interval 1.15-1.55) for the money reward and 1.22 (95% confidence interval 1.05-1.41) for the reminder card. Follow-up mailings to all nonrespondents included both incentives. At the end of data collection, 1,007 persons (82%) had returned the questionnaire. The final response rates were 83, 84, 82, and 78% in the four groups, respectively (p = 0.29). Both the promise of a monetary reward and a reminder postcard considerably improved early response rates. The use of both incentives in follow-up mailings brought final response rates above 80%, except for those who had received no initial incentive. Testing various combinations of incentives in the early stages of a mailed health survey may be a generally useful strategy.", "High response rates from physicians are key to obtaining valid and generalizable data regarding their sexually transmitted disease (STD) diagnosis, treatment, and control practices. A factorial (3 x 2) study was designed using varying cash incentives ($0, $15, $25) and delivery modes (Federal Express, U.S. mail). Surveys, with three follow-up mailings, were sent to a national probability sample of 311 physicians in OB-GYN, family practice, internal and emergency medicine, and pediatrics specialties. Overall, 156 physicians returned completed surveys (56% overall response rate). Significant effects for incentive level (F = 28.2, df = 2, p < .01) and delivery mode (F = 4.1, df = 1, p < .05) existed. Highest response was among physicians in the $25-FedEx condition (81%). High response rates from busy practicing physicians can be achieved if surveys are relevant to clinical practice, sponsored by a reputable organization (the Centers for Disease Control and Prevention), include a monetary incentive, and are delivered by courier.", "Maximizing the response rate of self-administered questionnaires is key in survey research. We aimed to evaluate the effects of lottery incentive and length of questionnaire on health survey response rates when used in isolation or combined. A random sample of 440 residents in Western Sydney, Australia was randomly allocated to four equal groups to receive or not receive an instant lottery ticket and a long (seven page) or short (one page) questionnaire. The overall response rate was 71.8%. The final response rates were higher among those receiving the short, rather than the long, questionnaire (75.6% versus 68.2%) (P = 0.08); and among those receiving the lottery incentive compared with those not receiving the incentive (75% versus 68.2%) (P = 0.09). By logistic regression analysis, the success of obtaining a completed questionnaire without any follow-up reminders was significantly associated with the lottery incentive but not the questionnaire length (P = 0.03 and P = 0.54, respectively). The difference between lottery and no lottery groups decreased gradually during the follow-up. A lottery incentive is associated with an increased response after the first mailing. A small up-front cost for a lottery ticket may be worthwhile, since it can save further costs by obviating the need for repeated follow-ups.", "In 1989, the authors tested the effectiveness of two response-enhancing techniques, a postage stamped or franked return envelope and a prenotification letter, in a survey of pregnancy among 10,047 resident physicians in the United States. The techniques were randomly assigned using a factorial design. No significant interactions were observed between the techniques. After two mailings, those who received a stamped return envelope had a response of 71.2%, compared with 68.2% for those who received a franked return envelope (95% confidence interval 1.3-4.9%). Men who received the stamped envelope had a 5.9% greater response than those who received the franked envelope (p less than 0.001), but the type of postage did not influence response among women (p = 0.84); this interaction was statistically significant (p = 0.006). Physicians who received a prenotification letter had a response of 69.0%, compared with 70.5% for those who did not receive the letter (95% confidence interval -3.3 to 0.2%). The authors conclude that seemingly minor changes in survey design could have saved from 12% to 19% of the total cost of the study.", "As part of a mailed health survey, we investigated the effect on the response rate of a request to explain refusal to participate. Subjects (N = 1,240) were randomized either to receive or not to receive, with the first mailing, a letter requesting an explanation of their decision not to fill out the questionnaire, if they chose that option. There was a slightly higher cumulative response during most of the study from subjects who had been sent the request, but little difference between the two study groups in the ultimate response rate [80% from the intervention group vs 83% from the control group; response rate difference = -3%; 95% confidence limits (CL) = -7%, 1%]. Of 209 individuals who were sent the request and did not return the questionnaire, only 15 (7%) sent back an explanation. A request to explain a refusal to participate in a mail survey neither jeopardized the response rate nor enhanced it.", "A mailed questionnaire was sent to 2712 subjects asking about respiratory symptoms, and a raffle for three prizes of 50 pounds, 30 pounds, and 20 pounds was organised. The response rate in the 1762 who were told about the raffle was no higher than for 950 subjects who served as controls.", "Our aim was to analyze monetary incentives and shortening the questionnaire as means of increasing response rates in a mailed follow-up survey 1 year after inpatient psychotherapeutic treatment. Additionally, effects on partial nonresponse and the assessment of treatment outcome were examined.\n In a 2x2 factorial design, a sample of 3,825 patients was randomized to the two following interventions: (1) receiving a prepaid monetary incentive or none; and (2) getting a short or a long questionnaire. Treatment outcome was measured prospectively by a self-assessment instrument for psychopathology.\n When using incentives, the response rate significantly increased by 7.3% (95% confidence interval [CI] 2.6-11.9%). Receiving a short questionnaire led to an augmentation of the response rate of 3.7% (95% CI 0.9-8.3%), which was not significant. The corresponding odds ratios were significantly increased for monetary incentives (1.36; 95% CI 1.30-1.88), and when abridging the questionnaire (1.15; 95% CI 1.01-1.31). However, partial nonresponse and treatment outcome were independent of the two factors.\n Incentives and a shorter questionnaire led to higher return rates but did not affect partial nonresponse and self-report of treatment outcome in a randomized postal survey.", "Poor response rates affect the validity of results from postal questionnaires. The effect of three controllable factors upon response rates was examined in a recent study of patients' experiences and views of general practitioner services. The factors studied were the institution from which questionnaires were dispatched, the length of the questionnaire and the inclusion of a potentially sensitive question about ethnic origin. Questionnaires sent out by local Family Practitioner Committees were more likely to be returned than those sent out by a London-based independent research unit, but there were no differences in the nature of replies obtained. Neither the length of the questionnaire nor the inclusion of the potentially sensitive question affected response rates. The results of the study indicate that Family Practitioner Committees wishing to carry out postal surveys of users of general practitioner services can obtain satisfactory response rates.", "Patient surveys are commonly distributed at the end of a multicenter clinical trial. This Antiarrhythmics Versus Implantable Defibrillators (AVID) substudy prospectively explored the relationship between methods used in distributing a survey and the quantity of responses received. AVID was a multicenter, randomized trial comparing survival in arrhythmia patients treated with antiarrhythmic drugs versus implantable defibrillators. At study termination, a patient satisfaction survey was mailed to the 664 surviving participants. Questions included reasons for study participation, study benefits and problems and quality of care. Survey mailings were stratified by four factors in a 2x2x2x2 factorial design: delivery mode (overnight vs. regular mail), certificate of appreciation, timing of administration (\"early\" vs. \"late\") and cover letter signed by a physician versus coordinator. Patients were randomly assigned to received one of 16 combinations of these four factors. Clinical characteristics and response rates were evaluated. Patients were more likely to return surveys delivered by overnight mail (75% vs. 68%, p=0.04), with no certificate of appreciation enclosed (75% vs. 68%, p=0.05) and administered close to the time of study closeout (79% vs. 72%, p=0.085). Compared to the 184 nonrespondents, the 456 (71%) respondents were older, Caucasian, lived with others, were high school graduates and less likely to have Medicare/Medicaid or HMO insurance (p<0.03). Physician recommendation was the most common reason cited for trial participation. Main benefits included increased knowledge of their medical condition and improved health. Reported problems included parking, transportation and excess clinic wait time. This randomized study demonstrated that methods of patient survey distribution affect the survey return rate. Additional studies should explore mechanisms for maximizing return rates.\n Copyright 2002 Elsevier Science Inc.", "To assess whether print format (single-sided vs. double) and sender recognition (known vs. unknown) affect response and completion rates among physician survey respondents.\n Postal survey of 399 members of the Canadian Association of Emergency Physicians; 2 x 2 factorial design.\n Response rate was 69.4%. Single-sided printing yielded 7.4% (odds ratio OR = 1.41; 95% confidence interval CI = 0.90-2.20; P = 0.13), and a known sender yielded a 6.3% greater response rate (OR = 0.73; 95% CI = 0.47-1.14; P = 0.16). Overall item completion was 98.2%; items missed per respondent ranged from 1 to 14 out of 50. Print format and sender recognition interacted in predicting completion rate (OR = 13.33; 95% CI = 3.10-57.4; P = 0.001); completion was higher for double-sided printing with an unknown sender, and for single-sided printing with a known sender. Completion was also lower when response came after later mailouts (chi2(2) = 10.13; P = 0.006).\n Print format and sender recognition both yielded 6%-7% (nonsignificant) response rate differences. Survey completion rate varied even when overall item completion was high. Completion rate was useful for identifying subgroups likely to provide incomplete data (i.e., late responders), and may provide important information for subsequent surveys. Combining factors that on their own improve survey response may have unexpected consequences.", "nan", "This study tested the effect of questionnaire structure on response, speed of return, and content of answers in a postal survey. All 259 patients aged 30-59 years who consulted with back pain at four UK general practices from March to June 2001 were randomly allocated to receive either a traditionally or chronologically structured self-completion questionnaire. The response was higher and the returns quicker (P =.05) for the chronologic questionnaire. There were no statistically significant differences in completion rates or scores on the SF-36, Chronic Pain Grade, Hospital Anxiety and Depression Scale, or Roland-Morris Disability Questionnaire between the two types of questionnaire, and test-retest reliability was high for all scales. Changing questionnaire structure to make questions chronologic does not substantially affect the answers given, but may make a questionnaire more acceptable and easier to complete and speed up returns.", "nan", "There is little information on the effect of time on the assessment by the patient of quality of anaesthesia care. This study compared the patient's assessment of anaesthesia care after three different periods of time following discharge from hospital. Materials. Three groups of patients were assigned to receive a standardized, validated psychometric questionnaire either 1, 5, or 9 weeks after discharge from hospital. We measured response rate and the total mean problem score of six dimensions.\n Groups 1, 2, and 3 received 748, 743, and 723 questionnaires, respectively. The response rates including one reminder were 67.3 (95% confidence interval [CI] 63.9-70.6%), 64.5% (CI 61.1-67.9%), and 58.9% (CI 55.5-62.4%), respectively (Group 1 vs Group 3, P<0.001, and Group 2 vs Group 3, P<0.05). The total mean problem scores were not significantly different with 17 (CI 1.4%), 17 (CI 1.4%), and 15% (CI 1.3%), respectively. In two out of six dimensions ('Continuity of personal care by anaesthetist' and 'Nursing care in recovery room') significantly less problems were reported after 9 weeks. The other dimensions of the questionnaire showed no consistent differences between groups.\n The response rate is significantly lower at 9 weeks compared with 1 and 5 weeks after discharge. The total mean problem score remains unchanged but certain fields show fewer problems after 9 weeks compared with 1 and 5 weeks. Questionnaires on patient satisfaction with anaesthesia care should be sent within 5 weeks of discharge.", "Dentists currently practising within the Central Sydney Area were surveyed (n = 179). A randomized controlled trial was conducted to evaluate the effect of an advance telephone prompt (intervention group) compared with an advance letter prompt only (control group) in maximizing the response rate to a self-administered questionnaire. While the overall response rate was 83 per cent, the final response rate (89 per cent) from dentists in the intervention group was significantly higher than that from dentists in the control group (78 per cent) (chi 2 = 4.14, df = 1, p = 0.04). Advance telephone prompts are effective in maximizing the response rates from dentists and are recommended in future surveys of this professional group.", "nan", "The purpose of this study was to compare the performance of the 15-item Picker Patient Experience questionnaire (PPE-15) when embedded in a short form instrument as compared with a longer form measure.\n A postal questionnaire survey of patients recently discharged from two hospital trusts was carried out. Patients were randomized to receive the PPE-15 in either a four-page or a 12-page survey instrument.\n A total of 1445 questionnaires were mailed to patients in either four- or 12-page formats. A total of 949 (65.67 per cent) forms were returned. No difference in response rate was found between the two versions of the questionnaire. Item completion and psychometric properties of the PPE-15 were not found to differ significantly between the two arms of the trial.\n In this survey the length of questionnaire in which the PPE-15 was embedded had no impact in terms of response rate or data quality. Consequently, the results suggest that length of questionnaire, up to the 108 items included in the 12-page survey, is unlikely to adversely affect results on the PPE-15.", "A 4-factor, 16-cell experimental design was used to investigate the relationship between response rates of community hospitals to a survey conducted by the American Hospital Association (AHA) and 4 characteristics of the survey instrument, each varied dichotomously: the perceived length of the questionnaire, the order of questions, the orientation of the appeal made in the cover letter, and the presence or absence of a promise to share the results of the study with respondents. Response rate variations between the various cells were examined and multiple logistic regression was used to analyze the significance of the association between response rates and each of the four survey instrument variables while controlling for the effect of the others. At the same time, control was also maintained for the effects of five institutional characteristics of hospitals which a previous study had shown to have a significant relationship to response: bed size, location within or outside a standard metropolitan statistical area, AHA membership status, type of ownership, and form of control. The perceived length of the questionnaire and the order of questions were found to have a significant effect on response rates, but the orientation of the cover letter and a promise to share the results of the study with the respondents were found to be insignificant.", "Mailed surveys are widely used to collect epidemiological and health service data on cancer populations. Nonresponse can threaten the validity of surveys and various strategies, including the enclosure of modest incentives, are often used to increase response rates. A study was undertaken to determine whether response rate to a mailed survey differed with provision of immediate versus delayed incentives. A six-page mailed survey to ascertain dietary supplement use was sent to 1402 men who had been diagnosed with prostate cancer. Subjects were block randomized into two groups based on age (< or =65 years versus >65 years), race (white versus nonwhite), and disease status (locoregional versus distant). One group received a 30-min prepaid phone card concurrently with their blank survey (unconditional incentive), whereas the other group received the incentive only on receipt of their completed survey (conditional incentive). A 60% overall response rate was achieved, and no differences in response rates were noted between conditional and unconditional incentive groups (overall, as well as within defined age, race, and disease-defined strata). Nonwhites, however, were significantly less likely to respond than whites (P < 0.0001). In conclusion, acceptable response rates to a mailed survey can be achieved in a general population of cancer survivors using modest incentives. Given no differences in response rates using conditional versus unconditional incentives, the decision to provide immediate versus delayed incentives is one that should be considered on a study-specific basis, and a decision based primarily on cost. Other means, however, appear necessary to achieve acceptable response rates among minority group cancer survivors.", "This study's goals were to (a) determine whether sending a survey by certified mail results in a higher response rate from physicians compared to sending by first-class mail and (b) evaluate the cost-effectiveness of this method. The study sample was 409 physicians who were nonrespondents to two previous mailings of a medical specialty society survey. Eligible physicians were designated at random to receive a final mailing either by U.S. Postal Service certified mail including a return-receipt postcard or by first-class mail. There was a higher response rate from the certified mail group compared with the first-class mail group (41.3% versus 24.8%; relative risk = 1.66, 95% Confidence interval 1.25, 2.21). A cost-effectiveness analysis showed that the cost per respondent was higher using certified mail versus first-class mail in the third mailing ($2.77 versus $2.34). Thus, use of certified mail is effective in increasing survey response but more costly.", "To determine whether response rates to a mailed questionnaire sent to population control subjects could be increased through offer of a small incentive, half of the control subjects (n = 477) in a case-control study of renal cell carcinoma were randomly selected to receive a contact letter offering a lottery ticket if a completed questionnaire was returned; the remaining subjects (n = 477) received the same letter but with no mention of a lottery ticket. Overall response rates did not differ between the two groups (72.6% versus 74.4%), although a higher percentage of those offered a lottery ticket responded without follow-up (24.4% versus 18.5%). Binomial regression modeling of the effect of the lottery ticket offer, sex, age, and percent of urban dwellers on response indicated a significant effect only for percent of urban dwellers, the rate of response increasing with a decreasing percentage of urban dwellers. The effect of sex was of borderline significance (P = 0.05), with females having the higher rate of response.", "Measures of association in prospective studies can be distorted by incomplete follow-up. Various mailing strategies were used to contact 12,233 cohort members of the Health Professionals Follow-up Study who had not responded to three successive bulk-rate mailings. Response rates were highest, 79.5% overall, from participants who were sent a certified mailing in phase 1 (63.2%), followed by a repeat certified mailing to nonrespondents (44.3%). Although altering the physical appearance of the envelope and using other postal rates were tested, certified mail was the most effective approach for reaching study members who were nonrespondents to a mailed questionnaire.", "The authors conducted a randomized trial in Geneva, Switzerland, to assess whether response rates to a mailed survey could be increased by printing the questionnaire on green paper. The authors also conducted a meta-analysis of 10 experimental studies that tested the effect of colored questionnaires on response rates. The randomized trial showed no effect (relative risk of responding [RR] = 1.00). The meta-analysis showed that mailing questionnaires on pink paper increased response rates by 12% (RR = 1.12, 95% confidence interval = 1.01 to 1.25, p = 0.04). Other colors had no statistically significant effect (blue: RR = 1.03, p = 0.49; green: RR = 1.02, p = 0.23; yellow: RR = 0.96, p = 0.30). Overall, using colored instead of white paper had no effect (RR = 1.02, p = 0.17). Thus, printing questionnaires on colored paper does not substantially increase response rates in surveys, except for pink paper.", "To assess the effect of incentive size on response rates, data quality, and cost in a digestive health status mail survey of a community sample of health plan enrollees.\n The study population was selected from a database of enrollees in various health plans obligated to receive care at Park Nicollet Clinic-HealthSystem Minnesota, a large, multispecialty group in Minneapolis, Minnesota, and the nearby suburbs.\n A total of 1,800 HealthSystem Minnesota enrollees were randomly assigned to receive a survey with an incentive of $5 or $2. The response rates for each incentive level were determined. Data quality, as indicated by item nonresponse and scale scores, was measured. Total cost and cost per completed survey were calculated.\n The response rate among enrollees receiving $5 (74.3 percent) was significantly higher than among those receiving $2 (67.4 percent); differences were more pronounced in the first wave of data collection. Data quality did not differ between the two incentive groups. The total cost per completed survey was higher in the $5 condition than in the $2 condition.\n A $5 incentive resulted in a higher response rate among a community patient sample with one mailing than did a $2 incentive. However, the response rates in the $2 condition approached the level of the $5 incentive, and costs were significantly lower when the full follow-up protocol was completed. Response rates were marginally increased by follow-up phone calls. The incentive level did not influence data quality. The results suggest if a survey budget is limited and a timeline is not critical, a $2 incentive provides an affordable means of increasing participation.", "In a follow-up study, only 64% of 126,628 US radiologic technologists completed a questionnaire during 1994-1997 after two mailings. The authors conducted a randomized trial of financial incentives and delivery methods to identify the least costly approach for increasing overall participation. They randomly selected nine samples of 300 nonresponders each to receive combinations of no, 1.00 US dollar, 2.00 US dollars, and 5.00 US dollars cash or check incentives delivered by first-class mail or Federal Express. Federal Express delivery did not achieve greater participation than first-class mail (23.2% vs. 23.7%). In analyses pooled across delivery methods, the response was significantly greater for the 2.00 US dollar bill (28.9%, 95% confidence interval (CI): 25.2, 32.7; p < 0.0001), 5.00 US dollars check (27.5%, 95% CI: 22.5, 33.0; p = 0.0001), 1.00 US dollar bill (24.6%, 95% CI: 21.2, 28.3; p = 0.0007), and 2.00 US dollars check (21.8%, 95% CI: 18.5, 25.3; p = 0.02) compared with no incentive (16.6%, 95% CI: 13.7, 19.9). The response increased significantly with increasing incentive amounts from 0.00 to 2.00 US dollars cash (p trend < 0.0001). The 2.00 US dollar bill achieved a 30% greater response than did a 2.00 US dollars check (p = 0.005). For incentives sent by first-class mail, the 5.00 US dollars check yielded 30% greater participation than did the 2.00 US dollars check (p = 0.07). A 1.00 US dollar bill, chosen instead of the 2.00 US dollars bill because of substantially lower overall cost and sent by first-class mail to the remaining 42,717 nonresponders, increased response from 64% to 72%.", "Randomized trials were performed in Denmark and The Netherlands to determine the effect of mailed reminders on the response rate in surveys among patients in general practice. In both countries, general practitioners handed out questionnaires to 200 adult patients who came to visit them. An intervention group of 100 patients received reminders at 3 weeks after the visit, whereas a control group of the remaining 100 patients did not receive reminders. The response rate was significantly higher in the intervention groups than in the control group in The Netherlands (86% versus 55%, respectively) but not in Denmark (87% versus 81%, respectively). Mailed reminders can improve the response rate in surveys related to a general practice, but they are not effective in all situations.", "Traditional measures of socioeconomic status may not be reliable for older people and income may be a useful measure for research into inequalities in health. At the same time, researchers increasingly wish to link survey findings to individual data taken from medical records. For this, consent must be sought. To examine whether questions on household income and seeking consent for medical record linkage affected response rates, a postal health survey of patients aged 65 to 74 was undertaken in an inner London practice. The overall response rate was 62.8%. In this study, the inclusion of an income question or seeking consent to access medical records did not reduce response rates to a health survey among older people.", "A health-related mailed survey was conducted to investigate the effect of follow-up mailings to response rates. In addition, the answer distributions among early and late respondents were compared to check non-response bias. Approximately 3,000 persons aged 40-64 were randomized into two groups; a questionnaire with four pages (twenty-two questions) was assigned to the first group, and a questionnaire with eight pages (thirty-five questions) to the second group. Both questionnaires contained questions of current health status, health-related practice, smoking status, etc. Follow-up mailings were sent twice to non-respondents. Response rates were increased from 38% to 62% by the first follow-up mail, and to 71% by the second follow-up mail. Although the length of the questionnaire did not affect response rates, response rates among the older subjects was higher than the younger subjects. Positive response to current smoking status was 10% lower among early respondents than late respondents, collected after the second follow-up mailing, and response to regular participation in physical/medical checkup was 15% higher among early respondents, whereas there were few differences for answers to other questions. Odds ratios between current health status and several health-related questions may not be biased by late response. However, increased response rates are needed to prevent non-response bias, because there were some differences in responses from follow-up mailings.", "To determine whether follow-up phone calls improve response rates to a long questionnaire among black and white subjects.\n Forty black and 39 white Seventh-day Adventist churches were randomized to experimental or control status in a 2:1 ratio favoring the intervention, which is a follow-up phone call to certain church members. Subjects selected from each church were those who had signed up for the Adventist Health Study-2 but not returned a questionnaire 3 months after promotion began. Further returns from a church over the next 3 months, and this increment as a proportion of baseline response, were assessed using t-tests and Poisson regression, respectively.\n Comparing black experimental and control churches, the mean difference was 5.5 returned questionnaires per church (p < 0.01). Among white churches the mean difference was 3.0 (ns). The baseline-adjusted increment, however, was greater by a factor of 3.37 (95% confidence interval, 1.92, 5.93) in the black experimental relative to control churches, but among white experimental churches was 13% (ns) lower than controls. This difference in response by ethnic group was statistically significant (p < 0.01).\n Follow-up phone calls improved response rates among black subjects only.", "A self-report questionnaire is the most widely used method to assess (in)patients' satisfaction with (hospital) care. However, problems like nonresponse, missing values, and skewed score distributions may threaten the representativeness, validity, and reliability of results. We investigated which of alternative item-response formats maximizes desired outcomes.\n Five formats were compared on the basis of sample characteristics, psychometric properties at the scale and item levels, and patients' opinions of the questionnaire.\n Consecutively discharged patients (n=784) were sampled, of which a representative (sex, age, length of hospital stay) subsample of 514 (65%) responded.\n A 54-item satisfaction questionnaire addressing 12 aspects of care was used. Patients responded using either a 10-step evaluation scale ranging from \"very poor\" to \"excellent\" (E10), a 5-step evaluation scale ranging from \"poor\" to \"excellent\" (E5), or a 5-step satisfaction scale ranging from \"dissatisfied\" to \"very satisfied\" (S5). The 5-step scales were administered with response options presented as either boxed scale steps to be marked or words to be circled.\n E5 scales yielded lower means than S5 scales. However, at the item level, the S5 scale showed better construct validity, more variability, and less peaked score distributions. Circling words yielded fewer missing item scores than marking boxes. The E5 scale showed more desirable score distributions than the E10 scale, but construct validity and reliability were lower.\n No large differences among formats were found. However, if individual items are important carriers of information, a (5-step) satisfaction response scale, with response options presented in words next to each item, appears to be the optimal format.", "Mailed surveys are a popular means of obtaining data on large populations. In July 1999 a mail survey was conducted among 3000 randomly selected members of the American Society of Hematology to assess their approach to diagnosis and treatment of polycythemia vera. Because the researchers and the study population are members of the same professional organization with a vested interest in the results, we anticipated that the advantages of return stamped postage seen in previous studies would be less significant. The response rate for stamped return envelopes was 38% versus 32% for business reply envelopes. This statistically significant difference (P =.0005) of six percentage points is comparable to previous research. Excluding labor, the total cost per returned survey was $2.62 for business reply envelopes versus $1.82 for stamped return envelopes. We conclude that stamped return envelopes are a more effective and cost-efficient means of procuring data from physician specialists.", "To evaluate whether small monetary incentives improve physicians' responses to surveys. To the best of the authors' knowledge, no one has evaluated emergency physicians' response rate and cost per participant of a small monetary incentive relative to a chance to win a more substantial sum. The authors compared emergency physicians' responses and per-participant costs between a US 2 dollar bill and a 250 US dollars lottery.\n Two groups of 288 emergency physicians were randomly selected and mailed a survey. Within each group of 288, half received a US 2 dollar bill and the other half received an offer that respondents would be entered into a drawing to win 250 US dollars. Nonresponders received a reminder postcard one week later, and persistent nonresponders received a second mailing of the survey three weeks after the initial mailing.\n Of the 576 surveys that were mailed, nine (2%) subjects were ineligible or undeliverable, leaving 567 eligible subjects, of whom 301 (53%) participated in the survey. The US 2 dollar bill had a substantially higher response rate: 170 (56%) of those receiving a US 2 dollar bill participated versus 131 (44%) of those receiving a chance to win 250 US dollars (95% confidence interval = 5% to 22%; p < 0.001). The US 2 dollar bill offer was less expensive per participant than the 250 US dollars offer. The cost of postage and incentives was 997.33 US dollars for 170 participants, or 5.87 US dollars per participant, for the US 2 dollar bill and 979.29 US dollars for 131 participants, or 7.48 US dollars per participant, for the chance to win 250 US dollars.\n Mailing a US 2 dollar bill incentive produces a better response rate with lower cost per participant than offering a chance to win 250 US dollars.", "Mailed questionnaires are a quick and cheap means of obtaining data, but they have two disadvantages. They often produce low response rates irrespective of the nature of the group sampled, and they may seem inappropriate for clinical samples with visual problems. High response rates are needed for reliable results and valid conclusions. This paper presents a set of techniques enabling high response rates to be obtained. It also reports research showing that such techniques are appropriate even for the partially sighted.", "Low response rates to surveys are a problem in general practice. There is evidence that offering GPs incentives improves response rates to postal questionnaires. However, there is less evidence about the most effective form of incentive.\n Our trial aimed to maximize response to a postal questionnaire and to test the most effective form of incentive.\n The study involved a randomized controlled trial of a postal survey\n The incentive of a lottery for six bottles of champagne generated a response rate of 79%. Furthermore, one chance of six bottles generated 9% more responses than six chances of one bottle.\n This study has established that, among incentives for postal questionnaires, one big prize improves the yield more than many small prizes despite the lower odds of winning. It has also confirmed that offering a modest incentive to GPs generates good response rates for postal questionnaires.", "This study examined return rates for a cancer prevention survey by pediatricians in relation to an informational booklet versus a monetary incentive in the first of a three-wave mailing. Of the 300 surveys sent which included an informational booklet incentive, 189 (64%) were returned. Of the 300 surveys sent which included a $1.00 incentive 227 (79%) were returned, indicating the $1.00 incentive was more effective than the informational incentive in increasing return rates in this sample of physicians.", "Primary care physicians are increasingly being asked to participate in postal surveys. Difficulties in achieving adequate response rates among physicians have been reported. We investigated the effect of two low-cost interventions on response to a primary care physician postal questionnaire.\n A 2x2 factorial trial was developed within the context of a national survey assessing views and practices of physicians regarding prostate-specific antigen testing. We evaluated questionnaire order (version 1: demographics first, version 2: topic-specific questions first) and written precontact. A national database of primary care physicians was compiled. One thousand five hundred ninety-nine physicians were randomly selected, stratified by health board, and randomized.\n 47.9% of eligible physicians completed a questionnaire. There was a statistically significant 5.1% higher response rate among physicians receiving version 1 of the questionnaire than those receiving version 2 (50.6% vs. 45.4%, P=0.05); the adjusted odds of response were significantly raised (odds ratio=1.24; 95% confidence interval=1.01-1.54). Precontact resulted in a nonsignificant 3.6% increase in response (49.8% vs. 46.2%; P=0.16). The interventions did not interact.\n Ordering questionnaires with general questions first can significantly increase response rates, whereas precontact can achieve a modest increase. These strategies may enhance response while adding little to the cost of a physician survey.", "The feasibility of collecting DNA through the mail from a cohort of current and former smokers was assessed. Also examined was whether monetary incentives would increase response rates. A random sample of 300 subjects, stratified by 20 U.S. communities, was selected to participate. The sampling frame included the 6,726 people who were in both the Community Intervention Trial for Smoking Cessation (COMMIT) between 1988 and 1993 and the follow-up study in 2001, and who consented to being contacted again. Subjects were further randomized within communities to incentive arms of 10 US dollars, 2 US dollars, or 0 US dollars. A total of 110 usable samples were returned (37%), and the 10 US dollars incentive arm had the highest response (43%). Logistic regression revealed no significant predictors of sending a DNA sample, although in a larger study, similar-sized odds ratios would be statistically significant for subjects who received the 10 US dollars incentive and for those who were White, female, or college graduates or whose household incomes were more than 60,000 US dollars per year. The spectrophotometer-determined median DNA yield was 44.93 microg (range=4.00-425.86 microg). Assuming that 50 ng of DNA would be needed for polymerase chain reaction amplification to determine any given genotype, 80-8,517 runs would be attainable. Qualitative findings suggest several methodological improvements to boost response rates. Institutional review board requirements, which are standardized on the inpatient, clinical protocol model, stipulated that noninstitutionally based subjects needed a witness to initial and date every page as well as sign the consent form. This pilot study showed that this requirement could pose some challenges in population-based research.", "To test the effect of a AU dollars 2 scratch lottery ticket on response rates to a national mailed questionnaire of Australian general practitioners (GPs) and medical specialists.\n A randomized controlled trial was conducted and the incentive sent to half of the participants with the first mailing. A single follow-up mailing without incentive was sent to all non-respondents. Survey respondents were then informed of the research question regarding incentives and allowed to withdraw their study data. Differences in response rates between doctors receiving and not receiving the incentive, and between respondents and non-respondents, were examined.\n The overall response rate was 47% (443 respondents). Twenty-two respondents (5%) withdrew their data after being informed of the research question. Of the remaining 421 respondents, 233 had received the incentive (response rate 49.7%) and 188 had not (40.1%, p=0.0032). The absolute increase in response rate with the incentive (9.6%, 95%CI 3.2, 15.9) was quantitatively similar in effect to the reminder mailing (11.8%). The incentive had a larger effect among the GP sample compared with specialists (13.4 vs. 5.9%), although the difference was not statistically significant (p=0.20). There were no systematic differences in demographic characteristics between respondents and non-respondents.\n Increased response rates associated with a small incentive may reduce the need for a second mailed reminder, but strong views about the use of incentives may negatively influence the participation of some practitioners. While the overall response rate was low, there was no evidence of bias in our sample.\n Copyright (c) 2005 John Wiley & Sons, Ltd.", "Monetary incentives in survey research may provide important gains from a methodological perspective in the control and reduction of survey error associated with potential nonresponse of participants. However, few studies have systematically investigated the use of monetary incentives or other methods to improve the response rates in the nonphysician clinician population.\n To investigate differences in response rates to a mailed self-administered survey of nonphysician clinicians who were randomized to receive a prepaid monetary incentive, a postsurvey prize drawing, or no incentive.\n A randomized controlled trial of financial incentives was conducted from November 2002 to February 2003. Nonphysician clinicians (nurse practitioners [NPs] and physician assistants [PAs]; N = 3,900) randomly selected to participate in a national ethics-related study were assigned randomly in equal allocations (n = 1,300 [650 NPs, 650 PAs]) to three incentive groups: (a) no incentive; (b) a $5 prepaid token incentive in the initial mailing; or (c) a chance to win one of ten $100 prize drawings upon completion and return of a self-administered survey.\n A $5 cash incentive increased survey response rates to an adjusted 64.2%: a 19.5 percentage point increase over the lottery group (44.7% response rate), and a 22 percentage point increase over the control group (42.2% response rate).\n A nominal cash incentive of $5 yields a significantly higher response rate from nonphysician providers than receiving either a lottery option or no incentive.", "Although not frequently used in Portugal, postal questionnaires allow the collection of information on patient's follow-up. In this study we assessed the rate of response and the usefulness of a postal questionnaire in a sample of patients with acute stroke. A prospective study was designed and analysed as a case-control: postal questionnaires were sent to 138 patients together with a randomly assigned stamped or post-free return envelope. The percentage of responders was 60% (n=78) and we found no significant differences in response rates according to the mailing strategy (58% for stamped and 62% for post-free return envelopes, p = 0.786). The time gap between hospital discharge and sending of the questionnaire had no significant influence in the response rate. Elder patients and women tend to respond more frequently, but these characteristics also do not change the response rate. Analysing socio-demographic variables reported at the acute phase, we only found differences in response rate for the smoking status: smoking was associated with a lower participation. In conclusion, the present study showed that a postal questionnaire is a useful method for the follow-up of stroke cases and that we must pay special attention to smokers for whom alternative strategies of contact or information should be used to increase compliance with postal questionnaire follow-up.", "Postal questionnaires are widely used to collect data in healthcare research but a poor response rate may reduce the validity and reliability of results. There was a lack of evidence available relating to use of a monetary incentive to improve the response rate in the healthcare setting.\n The MRC ORACLE Children Study is assessing the health and development of nearly 9000 seven year old children whose mothers' joined the MRC ORACLE Trial. We carried out a randomised controlled trial of inclusion of monetary incentive (five pound voucher redeemable at many high street stores) with the reminder questionnaire to parents. This trial took place between April 2002 and November 2003. When the parents were sent the reminder questionnaire about their child's health and development they were randomly assigned by concealed computer-generated allocation stratified by week of birthday to receive a five pound voucher or no incentive. The population were 722 non-responders to the initial mailing of a 12-page questionnaire. Main outcome measures: Difference in response rate between the two groups.\n Inclusion of the voucher with the reminder questionnaire resulted in a 11.7%(95% CI 4.7% to 18.6%) improvement in the response rate between the two groups.\n This improvement in response rate and hence the validity and reliability of results obtained appears to be justified ethically and financially.", "Prior research indicates survey procedures that signal significance and individualized mailings have higher response rates. Thus, it was hypothesized that surveys delivered via Priority mail would result in higher return rates than surveys delivered via First-Class. 260 surveys were sent to individuals randomly selected from lists of licensed physical and behavioral healthcare providers in Alaska and New Mexico. Half of the selected individuals were assigned randomly to receive mailings using Priority mail, the other half received First-Class mailings. Return rate was 39% for First-Class and 35% for Priority. Z tests of proportion indicated no statistically significant differences between methods. Given increased costs with no resultant increase in response rate, sending surveys to potential participants via Priority mail does not appear warranted.", "The authors randomly selected 400 physicians from a population of 1,545 practicing physicians providing follow-up care to patients who received bone marrow or blood stem cell transplants at the Fred Hutchinson Cancer Research Center to determine interest in receiving Internet-based transplant information. In a two-factor completely randomized factorial design, the 400 physicians were assigned to receive mailed surveys with either no compensation or a $5 check and either no follow-up call or a follow-up call 3 weeks after mailing. Overall, 51.5% of the physicians returned the mailed surveys. Comparison of logit models showed that inclusion of a $5 check in the mailer significantly (p = .016) increased the probability of returning the surveys (57.5% vs. 45.5%). In contrast, the telephone follow-up had no overall effect. The authors concluded a modest financial reward can significantly improve physician response rates to research surveys but a telephone follow-up may be inefficient and even ineffective.", "Although mailed surveys are an important component of epidemiological research, results from mailed surveys are often suspect because of poor response rates and the potential for nonresponse bias. Previous work has demonstrated that paying subjects to complete questionnaires increases response rates, but this work has not well addressed the impact of the timing of incentives on total cost, cost effectiveness, and response bias. We surveyed 400 university employees about health benefits. By random allocation, half received a check for $5 along with the mailed survey, and the other half received the promise of $5 on return of a completed survey. The response rates for both groups were about the same (64 and 59%, respectively), but prepayment was less expensive in aggregate and less expensive per response. In addition, we found that subjects with lower salaries were more likely to respond when paid in advance. We conclude that prepayment may actually be less expensive and more cost effective than payment on completion, but that the timing of payment may influence the profile of respondents.", "We conducted a pilot study to determine the most efficient mailing strategy for a postal questionnaire study among nurses in Ontario, Canada. Five mailing strategies involving types of stamps on the return envelopes were considered: no stamp, business-reply stamp, metered stamp, small regular stamp, and large commemorative stamp. We found that paper stamps, especially large commemorative stamps, on return envelopes increased the response rate and reduced the response time, as compared with other mailing strategies. Business-reply stamps had the lowest cost per response received and a low total cost.", "This study assessed efforts to increase response rates to a mailed physician survey and examined whether, as a result, nonresponse bias was reduced.\n Randomly selected physicians and geneticists were mailed a questionnaire concerning genetics knowledge and attitudes. In the final but not the pilot survey, a $25 incentive and intensive follow-up were used to increase the response rate.\n The response rate from physicians in the final survey was 64.8% (n = 1140), compared with 19.6% in the pilot test (n = 69). Sample representatives in sociodemographic and practice characteristics was improved by follow-up. Respondents recruited with more difficulty did not differ on the principal outcome variable, genetics knowledge, except on one subscore. Pilot study and final survey respondents did not differ in knowledge.\n Although the effect of increased response rates on the principal outcome variable in this study was minimal, this may not be the case for other studies. Every effort should be made to attain as high a response rate as is practical and to establish that respondents are representative of the population being sampled.", "To test alternative response formats for the Nottingham Health Profile (NHP), in terms of acceptability, score distributions, and measurement properties.\n Randomized trial of four response formats for the NHP: original \"yes/no\" format, a 3-point similarity format (\"applies completely/in part/not at all\"), a 5-point intensity format (\"completely true\" to \"completely false\"), and a 5-point frequency format (\"all the time\" to \"never\"). Respondents were patients discharged from a hospital. We compared scores distributions, reliability coefficients, correlations with dimension-specific numerical scales, and patient ratings of the instrument.\n Response rates were similar for the four versions. The original response format had the fewest fully completed questionnaires, and the largest ceiling effects. Internal consistency and test-retest coefficients were acceptable for all versions, but were higher for the two 5-point formats. Correlations reflecting convergent and discriminant validity were higher for the longer response formats than for the original version. The frequency format received the highest ratings from patients, particularly from the sicker and older subgroups.\n The psychometric performance and patient acceptability of the NHP can be improved by using a 5-point frequency response format instead of the original dichotomous response format.", "The authors examined differences in rate of response, data quality, and cost between mail approaches and in-person interview in the collection of data on sexual history and personal behaviors. A sample of women from a midwestern United States university (n = 342) was identified from health service medical records as having been seen for a sexually transmitted disease (cases) or a contraceptive visit (controls) during the latter half of 1985. The women were randomly assigned to one of three data collection strategies. A total of 268 subjects (78%) participated. Results indicated no differences in validity by method of data collection or by case-control status but there were significant differences in completeness, cost, and response rates. In-person interviews resulted in more complete data than mail approaches, although all instruments had low proportions of missing data (0.001-0.006). Response rate differences were not found when data collection methodologies were compared (75-82%) but were found in case-control analyses. Cases were consistently less likely to participate and significantly less likely to respond by mail (p less than 0.05). The cost of the in-person interview was approximately four times that of the mail survey for the data collection. Implications of the case-control response rate difference suggest that mail methodologies, although low in cost, may introduce sampling bias in studies of sexually transmitted diseases.", "Improving response rates, particularly among physicians, is important to minimize nonresponder bias and increase the effective sample size in epidemiologic research. We conducted a randomized trial to examine the impact of prepayment vs. postpayment incentives on response rates.\n Self-completion postal questionnaires were mailed to 949 physicians who were respondents to an earlier survey and representative of the general physician population in Hong Kong. These physicians were randomly allocated to receive a HK dollar 20 cash prepayment incentive that accompanied the survey (n=474) or a postpayment reward of the same amount on receipt of the completed questionnaire (n=475).\n The final prepayment response rate was 82.9%, compared with 72.5% in the postpayment arm (P < .001). Of the eight alternative incentive and follow-up strategies evaluated, three lie on the efficiency frontier (i.e., not dominated), including postpayment with three mailings at HK dollar 42.7, prepayment with three mailings at HK dollar 66.5 and prepayment with three mailings and telephone follow-up at HK dollar 112.1 per responder recruited (US dollar 1=HK dollar 7.8).\n The findings demonstrate that prepayment cash incentives are superior to postpayment of the equivalent amount in improving response rates among a representative sample of Hong Kong physicians. Further research should concentrate on confirming the generalizability of these findings in other health care occupation groups and settings.", "To determine the effect of different methods of administering a diary to collect information from parents on near miss and minor injuries on responses, completeness and accuracy, the number of incidents reported, the effect of a financial incentive on response, and the cost of administering each method.\n The study was set within the context of a cluster randomised controlled trial of injury prevention in 36 practices in Nottingham.\n The study population comprised the 1594 parents who responded to the baseline questionnaire. Parents were allocated systematically to one of four groups: postal administration, with and without financial incentive, telephone administration, with and without financial incentive (102 in each group). A clinic visit method with and without financial incentive (50 in each group) was also used.\n A significant trend was found, with decreasing response rates with increasing degree of contact with the parent, such that administering the diary in the clinic had the lowest response (chi2 for trend = 5.54, 1 df, p = 0.02). Offering a financial incentive increased responses from 47% to 59% (chi2 = 5.78, 1 df, p = 0.016). The most complete recording was found in the diaries handed out at clinic visits. Importantly, parents were accurate in their recording of near miss and minor injuries, suggesting they understood the differences between the two types of incident. Postal methods were the least expensive method of administering the diary in terms of average cost per returned diary. Using a financial incentive resulted in a lower cost per returned diary for telephone and clinic visit methods.\n Parents can accurately and reliably complete diaries recording near miss and minor injuries occurring to their preschool children. More work is needed to investigate methods of increasing response. Postal diaries achieve the highest response but have the least complete recording of data. Diaries administered through child health clinics were most complete but achieved the lowest response. The administration method chosen in future work should be influenced both by the response and completeness of recording that is required by the research.", "The objective of this study was to compare the impact of closed- versus open-ended question formats on the completeness and accuracy of demographic data collected in a mailed survey questionnaire. We surveyed general internists in five Canadian provinces to determine their career satisfaction. We randomized respondents to receive versions of the questionnaire in which 16 demographic questions were presented in a closed-ended or open-ended format. Two questions required respondents to make a relatively simple computation (ensuring that three or four categories of response added to 100%). The response rate was 1007/1192 physicians (80.0%). The proportion of respondents with no missing data for all 16 questions was 44.7% for open-ended and 67.0% for closed-ended formats (P < 0.001). The odds of having missing items remained higher for open-ended response options after adjusting for a number of respondent characteristics (2.67, 95% confidence interval 2.01 to 3.55). For the two questions requiring computations focused on professional activity and income, there were more missing data (P = 0.02, 0.02, respectively) but fewer inaccurate responses (P = 0.009, 0.20, respectively) for the open-ended compared to the closed-ended format. Investigators can achieve higher response rates for demographic items using closed format response options, but at the risk of increasing inaccuracy in response to questions requiring computation.", "nan", "It is becoming increasingly difficult to obtain high response rates in physicians' mail surveys. In 1983-84, we tested the effectiveness of two techniques among 604 Quebec physicians who had not responded to an initial letter. A handwritten thank you note at the bottom of the letter accompanying the questionnaire and a more personalized mailout package increased response rates by 40.7 per cent and 53.1 per cent, respectively, compared to control groups.", "To assess the impact of patient satisfaction survey method on response rate, data quality and satisfaction.\n Four modes of data collection were assessed during a randomized trial that included 400 inpatients discharged from a teaching hospital.\n The response rate was 58% within the mail survey group (72% with follow-up letter) versus 73% and 81% within the home and telephone interview group (p < 0.01). 69% of the mailed questionnaires contained no missing values versus 94% and 96% for home and telephone interview modes (p < 0.01). The global satisfaction scale score was greater within the mail survey groups (8.1/10 without follow-up letter and 7.9 with follow-up letter) than within the telephone interview group (7.8) and the face to face interview group (7.3), (p < 0.05).\n Mail survey with follow-up letter constitutes an operational method despite lower data quality and overestimation of patients' satisfaction scores.", "The validity of the results of mailed surveys is often threatened by nonresponse bias, which is made more likely when response rates are low. However, the effectiveness and cost-effectiveness of several strategies to increase response rates are uncertain.\n To assess three strategies to increase response rates to mailed physician surveys: including a 10 dollars versus a 5 dollars cash incentive in the initial mailing, including a mint candy or not, and using a large versus small outgoing envelope.\n Using a 2 x 2 x 2 factorial design, a randomized trial of these strategies was conducted in a survey of 1200 physicians randomly selected from the American Medical Association's Master File.\n Including a 10 dollars incentive yielded a significantly higher response rate (60.5% vs. 52.8%) (P = 0.009). The mailing and incentive costs per completed response were 12.24 dollars (95% CI, 11.75 dollars, 13.64 dollars) in the 5 dollars group and 18.48 dollars (95% CI, 17.77 dollars, 20.69 dollars) in the 10 dollars group. Each additional response obtained in the 10 dollars group came at an incremental cost of 61.26 dollars (95% CI, 36.98 dollars, 200.80 dollars). Neither inclusion of a mint nor use of a large envelope influenced the response rate.\n Investigators may increase response rates by including more money in the initial questionnaire packet, but there may be diminishing returns to serial increments in incentives greater than 5 dollars. Including smaller incentives in more questionnaires may maximize total responses.", "To study the effect of a lottery incentive on questionnaire response rate.\n In Copenhagen County, Denmark, a random sample of 2543 men and women between the ages of 19 and 60 were randomised into a control group and an intervention group. Both groups were contacted by mail and asked to complete a questionnaire on sociodemografic characteristics, self-rated health and self-reported physical activity level. The intervention group was offered participation in a small lottery for returning the questionnaire. No incentive was offered to the control group.\n The final response rate for the control group was 60.4 and 63.4% for the intervention group. Although the response rate was significantly higher in the intervention group after 2 and 3 weeks, the difference in the final response rate between groups was not statistically significant (p = 0.12). There was no statistically significant difference between groups in sociodemografic characteristics, self-rated health or self-reported physical activity level.\n A lottery incentive had no significant effect on the overall response rate, but may have contributed to a quicker response. Furthermore a lottery incentive did not seem to alter the selection of respondents.", "There is substantial interest in use of the Internet for surveys, but there have been few health-oriented, large, randomized trials of general population surveys on the Internet. It is unclear whether providing the option to respond via Internet increases the response rate, and to what degree the results will differ.\n The aim of the study was to evaluate changes in response rate and outcomes in a postal respiratory health survey by adding an optional Web response alternative.\n This was a randomized trial of a random sample of 4213 permanent residents of Norway, aged 20-40 years. Participants were randomized into a traditional survey arm, where they were asked to return the survey by mail, and an arm where they were also offered the option to respond via a Web form.\n A total of 1928/4213 subjects responded, a response rate of 45.8% across both arms. The total response rate was 44.8% (944/2105) in the postal plus optional Internet response arm and 46.7% (984/2108) in the usual postal survey arm, with no statistically significant difference between the randomized groups (P = .24). In the optional Internet arm, 8.3% (175/2105) of the sample responded using the Internet and 36.5% (769/2105) responded by post. Thus, Internet response was chosen by 18.5% (175/944) of those who replied in the optional Internet arm. In the multivariate analysis, Internet response was associated with being male, frequency and type of Internet access (home users more likely to respond by Internet than work users), and smoking habit, with current smokers being more likely to be Internet responders. 57% preferred postal response (1102/1928), 38% preferred Internet response (733/1928), and 3% preferred telephone interview (54/1928), with no difference between randomization arms (P = .56). But among those who indicated that they preferred the Internet response and who were randomized to the optional Internet arm, only 47% actually chose the Internet response. Asthma prevalence was higher among participants choosing the Internet response mode (16.7% vs 12.4%).\n We failed to increase survey response rates by adding an optional Internet response. Asthma diagnosis was higher in the Internet response group, suggesting nonresponse bias. Method comparison studies should be carried out before Internet studies are accepted in new populations or new subject matters.", "Studies largely from the market research field suggest that the inclusion of a stamped addressed envelope, rather than a pre-paid business reply, increases the response rate to mail surveys. The evidence that this is also the case regarding patient mail surveys is limited.\n The aim of this study is to investigate whether stamped addressed envelopes increase response rates to patient mail surveys compared to pre-paid business reply envelopes and compare the relative costs. A sample of 477 initial non-responders to a mail survey of patients attending breast clinics in Greater Manchester between 1/10/2002 - 31/7/2003 were entered into the trial: 239 were randomly allocated to receive a stamped envelope and 238 to receive a pre-paid envelope in with their reminder surveys. Overall cost and per item returned were calculated.\n The response to the stamped envelope group was 31.8% (95% CI: 25.9% - 37.7%) compared to 26.9% (21.3% - 32.5%) for the pre-paid group. The difference (4.9% 95% CI: -3.3% - 13.1%) is not significant at alpha = 0.05 (chi2 = 1.39; 2 tailed test, d.f. = 1; P = 0.239). The stamped envelopes were cheaper in terms of cost per returned item (1.20 pounds) than the pre-paid envelopes (1.67 pounds). However if the set up cost for the licence to use the pre-paid service is excluded, the cost of the stamped envelopes is more expensive than pre-paid returns (1.20 pounds versus 0.73 pounds).\n Compared with pre-paid business replies, stamped envelopes did not produce a statistically significant increase in response rate to this patient survey. However, the response gain of the stamped strategy (4.9%) is similar to that demonstrated in a Cochrane review (5.3%) of strategies to increase response to general mail surveys. Further studies and meta analyses of patient responses to mail surveys via stamped versus pre-paid envelopes are needed with sufficient power to detect response gains of this magnitude in a patient population.", "To determine the degree to which mailed survey response rates, response times, and nonresponse bias are affected by questionnaire size and color.\n Questionnaires were mailed to a random sample of 2,000 Mayo Clinic patients in one of four size/color \"test\" groups. One thousand three hundred nine surveys were completed, approximately two-thirds in each group.\n A small (6 (1/8) x 8 (1/4) in) questionnaire booklet on white paper had a higher response rate (68.4%) than a similarly sized questionnaire on blue paper (62.3%). A large (8 (1/4) x 11 in) questionnaire on white paper had a 62.7% rate, whereas a large, blue questionnaire had a response rate of 68.6%. Median response times did not differ by questionnaire size/color. No evidence of differential nonresponse bias was observed across the four test groups.\n This study supports the use of a small/white questionnaire format advocated by the Total Design Method advanced by Don Dillman at Washington State University. We observed a favorable response rate for a large questionnaire printed on blue paper; however, if time and resources are limited, use of a small/white questionnaire appears preferable.", "nan", "A systematic review identified a range of methods, which can influence response rates. However, analysis specific to a healthcare setting, and in particular, involving people expected to be poor responders, was missing, We examined the effect of pre-warning letters on response rates to a postal survey of sedentary patients whom we expected a low rate of response.\n Participants were randomised to receive a pre-warning letter or no pre-warning letter, seven days before sending the main questionnaire. The main questionnaire included a covering letter and pre-paid return envelope. After seven days, non-responders were sent a reminder letter and seven days later, another reminder letter with a further copy of the questionnaire and return envelope.\n 627 adults, with a mean age of 48 years (SD 13, range 18 to 78) of whom 69.2% (434/627) were women, were randomised. 49.0% (307/627) of patients were allocated to receive a pre-warning letter and 51.0% (320/627) no pre-warning letter, seven days in advance of posting the main questionnaire. The final response rate to the main questionnaire was 30.0% (92/307) amongst those sent a pre-warning letter and 20.9% (67/320) not sent a pre-warning letter, with an adjusted odds ratio of 1.60 (95% CI 1.1, 2.30).\n The relatively low cost method of sending a pre-warning letter had a modest impact on increasing response rates to a postal questionnaire sent to a group of patients for whom a low response rate was anticipated. Investigators should consider incorporating this simple intervention when conducting postal surveys, to reduce the potential for nonresponse bias and to increase the study power. Methods other than postal surveys may be needed however when a low response rate to postal surveys is likely.", "To assess whether changing the layout of the SF-12 affected item response rates, we tested two SF-12 formats in a quasi-randomized trial of women aged >or=70 years in two general practices in North Yorkshire. The modified version of the SF-12 ('York SF-12') converted the 'stem and leaf' format of some questions to individual items. We assessed the effect of the two types of questionnaires on item response rates. The difference in overall response rates to the two questionnaires (York SF-12 26.8%; SF-12 29.5%) was not statistically significant (95%CI -1.88% to 7.22%). However, the modified SF-12 had a statistically significantly lower item non-response rate of 8.5%, compared with the 26.6% of the SF-12 (95%CI 11.1%-25.1%). Chronbach's alpha reliability scores for the York SF-12 were also slightly better than for the older version. The York version of the SF-12 is an improvement on the original questionnaire. We recommend that the York SF-12 be used in preference to the SF-12 when surveying an older population.", "Achieving acceptable response rates from health care providers via postal questionnaires is an ongoing challenge. The use of monetary incentives is one of the most effective strategies for increasing response rates. However, the effect and cost of such an incentive on retail pharmacists' response rates has not been well studied.\n A sample of 700 pharmacies was selected at random from the electronic Yellow Pages in NSW Australia and mailed a brief survey regarding pharmacotherapies and advice for smoking cessation. Half of the sample was randomly allocated to receive an offer of an 14 US dollars gift voucher.\n The response rates were 65.9% for the voucher group and 53.5% for the no-voucher group. The odds of response from the voucher group was 1.68 (95%CI = 1.23, 2.30) times greater than for the no-voucher group. The cost per additional respondent was 67.95 US dollars. The incentive also reduced follow up costs by 10%.\n A moderately sized monetary incentive is able to achieve a significant increase in response rates for retail pharmacists, thereby reducing potential bias in the sample.", "Response rates to postal questionnaires are falling and this threatens the external validity of survey findings. We wanted to establish whether the incentive of being entered into a prize draw to win a personal digital assistant (PDA) would increase the response rate for a national survey of consultant obstetricians and gynaecologists.\n A randomised controlled trial was conducted. This involved sending a postal questionnaire to all Consultant Obstetricians and Gynaecologists in the United Kingdom. Recipients were randomised to receiving a questionnaire offering a prize draw incentive (on response) or no such incentive.\n The response rate for recipients offered the prize incentive was 64% (461/716) and 62% (429/694) in the no incentive group (relative rate of response 1.04, 95% CI 0.96 - 1.13)\n The offer of a prize draw incentive to win a PDA did not significantly increase response rates to a national questionnaire survey of consultant obstetricians and gynaecologists.", "The effects of incentive size on physicians' response rates to a mail survey were determined.\n One thousand US primary care physicians were assigned randomly to receive a survey with either a $5 bill or a $2 bill as an incentive. For each of the two incentive groups, the overall response rate for three mailing waves, the total cost, and the total cost per usable response were measured.\n The response rate among those receiving the $5 bill (61%) was 32% higher than the response rate among those receiving the $2 bill (46%); overall costs were slightly higher in the $5 group, but the cost per response for each group was similar ($15.46 versus $14.93). For the same cost, a higher response rate could have been achieved in the $2 group if costs saved from foregoing the third mailing were instead used to increase the incentive for a portion of the subjects.\n A $5 bill incentive yielded a higher response rate among the physicians in this study than did a $2 bill incentive. Moreover, the powerful effect of the incentive size, combined with the consequent decline in the costs of subsequent mailing waves, suggests that resources in a fixed survey budget are allocated more efficiently to increasing the initial incentive rather than to providing a third wave to nonresponders.", "In a survey about euthanasia, 1,600 critical care nurses were randomly assigned to receive either three complete, anonymous mailings of the questionnaire or, with each mailing, a coded postcard to be returned separately from the questionnaire to reduce subsequent mailings to previous responders. The response rate in these two groups was 76.5% [95% confidence interval (CI) = 73.6-79.4%] and 69% (95% CI = 65.7-72.4%), respectively. The two strategies yielded similar responses, and costs were much lower for the postcard group. Using coded postcards to be returned separately from completed instruments appears to lower the response rate to anonymous mail surveys, but it also lowers cost and may not introduce additional bias.", "Effective strategies to maximize response rates to self-administered surveys of clinicians are crucial to minimize response bias. Offers of charitable donations have been assessed for their potential to promote participation of community samples but not in the context of medical specialist samples. We randomized all Australian colorectal surgeons (n = 219) to whom we mailed a survey about clinical practice guidelines to receive either a standard covering letter or one promising a donation to their peak professional organization upon our receipt of their completed survey. Contrary to expectations, surgeons advised that their participation would secure a donation to their college were significantly less likely to return their questionnaire (84.3%, 95% CI 76.0-90.5%) than those receiving a standard letter (93.7%, 95% CI 87.4-97.4%). They also were more tardy in their response (Hazard Ratio = 0.75, 95% CI 0.57-1.00) (P = 0.047). In this context, offering donations to surgeons was counterproductive in enhancing response rates.", "Self-administered questionnaires are commonly used in experimental studies to elicit quality of life or other outcomes. Hence, achieving an acceptable level of follow-up from patients is critical to minimizing bias. Many methods for maximizing follow-up remain untested. It is also unclear what level of follow-up is required to prevent bias being introduced.\n We recruited 246 men from general practice surgeries in Sydney, Australia. These 246 men were randomized to receive a covering letter with their follow-up questionnaire either advising of a deadline to reply (Deadline, n = 126) or a standard letter without a deadline (No Deadline, n = 120). Four standardized reminder prompts subsequently were administered. We calculated interim response rates and the final proportion of follow-up questionnaires received according to group. We also compared scores on two main outcomes, namely, knowledge and decisional conflict at each time when reminder prompts were administered.\n One hundred and twelve (88.9%) men in the Deadline group returned their follow-up questionnaires compared with 102 (85.0%) men in the No Deadline group. This difference was not statistically significant [odds ratio = 1.41, 95% confidence interval (CI) = 0.67-2.99; p = 0.36]. Time to response also was not significantly affected by cover letter received (hazard ratio = 0.96; 95% CI = 0.73-1.25; p = 0.76). Results of the original RCT were similar in terms of direction and effect size at all times irrespective of when reminder prompts were administered.\n The addition of a deadline adds no further impact in improving response rates from male patients compared with an unspecified letter. Despite the accepted wisdom that higher response protects against bias, differences in outcomes were consistent throughout the post-test data collection period.", "The purpose was to determine whether asking about ethnic origin and housing tenure in a postal survey affects the response rate.\n The study derived from a postal survey designed to determine eligibility for a study of outpatients. A two way factorial design was used to look at the two experimental factors, questionnaires being randomly divided into four groups with or without questions about ethnic origin and housing tenure.\n 10,000 people (1000 from each of 10 areas) were systematically sampled from electoral registers, the areas being chosen to give a nationally representative sample.\n The response rate was 66% irrespective of whether ethnic origin was asked about, but was 65% and 67% respectively to questionnaires with and without questions about housing tenure.\n Asking about ethnic origin did not affect the overall response to this survey although it is possible that the response from some ethnic minority groups was lower. Asking about housing tenure slightly, but significantly, decreased response.", "In this study, the authors sought to determine the effects of length and clarity on response rates and data quality for two food frequency questionnaires (FFQs): the newly developed 36-page Diet History Questionnaire (DHQ), designed to be cognitively easier for respondents, and a 16-page FFQ developed earlier for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The PLCO Trial is a 23-year randomized controlled clinical trial begun in 1992. The sample for this substudy, which was conducted from January to April of 1998, consisted of 900 control and 450 screened PLCO participants aged 55-74 years. Controls received either the DHQ or the PLCO FFQ by mail. Screenees, who had previously completed the PLCO FFQ at baseline, were administered the DHQ. Among controls, the response rate for both FFQs was 82%. Average amounts of time needed by controls to complete the DHQ and the PLCO FFQ were 68 minutes and 39 minutes, respectively. Percentages of missing or uninterpretable responses were similar between instruments for questions on frequency of intake but were approximately 3 and 9 percentage points lower (p < or = 0.001) in the DHQ for questions on portion size and use of vitamin/mineral supplements, respectively. Among screenees, response rates for the DHQ and the PLCO FFQ were 84% and 89%, respectively, and analyses of questions on portion size and supplement use showed few differences. These data indicated that the shorter FFQ was not better from the perspective of response rate and data quality, and that clarity and ease of administration may compensate for questionnaire length.", "Young adults who had previously participated in a longitudinal survey of youth were sent a questionnaire. They were randomly assigned to receive a $20 prepayment, a $20 postpayment, or a $25 postpayment for participation in the latest survey. Those in the large incentive condition were 7 percentage points more likely to return a survey than those in the smaller, postpayment group. Prepayment had a smaller, less reliable effect. Effects of incentive magnitude and timing were consistent at each month of the study period; only better high school grades distinguished early responders from late responders. Nonresponders had characteristics suggestive of low social conformity and were more likely than responders to be African American and male and have low SES. The discussion centers on motivations for participating in research and differences in the incentives likely to promote continued response versus initial study enrollment.", "A range of factors have been shown to affect the response rate to mailed questionnaires, but particular strategies to improve patients' response in trials conducted in general practice require further study.\n Non-responders in a larger trial were randomized to receive a telephone or recorded delivery reminder on the third contact. The cost of administration of each method was estimated.\n Significantly more patients returned completed questionnaires when sent questionnaires by recorded delivery, although the cost per patient contacted was nearly three times more than for contact by telephone.\n Our study indicates that sending reminders by recorded delivery, although more expensive, is more effective than telephone reminders for recruiting patients to a study in general practice using research questionnaires.", "The purpose of this study was to assess the impact of sponsorship of a mailed satisfaction survey on response patterns and patient satisfaction ratings, and to establish whether satisfaction ratings depend on the timing of response. The study was part of a patient satisfaction survey conducted in a medical group practice in Geneva, Switzerland. All persons who had received an outpatient visit at the medical practice in the last week of September 1993 were assigned randomly to receiving the survey package either on university letterhead or on the medical practice letterhead. Participation rates were 80.5% and 80.4% in the two groups, respectively. The sponsorship of the survey had no detectable impact on response speed or response completeness. Six out of seven satisfaction scores were higher in the \"medical practice\" group, but the differences were not statistically significant. As data collection progressed, the cumulative satisfaction rating decreased gradually. This association was statistically significant but moderate. Whether a satisfaction survey is sponsored by a university or a health care provider does not seem to affect survey results. However, low survey response rates may moderately bias satisfaction estimates toward higher values.", "Twins taking part in two unrelated studies were sent a questionnaire together with a self-addressed envelope that either carried one or multiple (up to 5) stamps to the same value. The unprompted proportion of questionnaires returned (before commencement of telephone reminder calls) was increased from 62% to 71% in one study, and from 43% to 52% in the other study (test for common odds ratio in studies, p = 0.04).", "Response rates to surveys are declining and this threatens the validity and generalisability of their findings. We wanted to determine whether paper quality influences the response rate to postal surveys\n A postal questionnaire was sent to all members of the British Society of Gynaecological Endoscopy (BSGE). Recipients were randomised to receiving the questionnaire printed on standard quality paper or high quality paper.\n The response rate for the recipients of high quality paper was 43/195 (22%) and 57/194 (29%) for standard quality paper (relative rate of response 0.75, 95% CI 0.33-1.05, p = 0.1\n The use of high quality paper did not increase response rates to a questionnaire survey of gynaecologists affiliated to an endoscopic society." ]

[ "15942550", "2005733", "2841662", "11978259", "11978262", "10720164", "11976158", "1846723" ]

[ "Cholesterol-lowering benefits of oat-containing cereal in Hispanic americans.", "The hypocholesterolemic effects of beta-glucan in oatmeal and oat bran. A dose-controlled study.", "Serum lipid response to a fat-modified, oatmeal-enhanced diet.", "Do whole-grain oat cereals reduce the need for antihypertensive medications and improve blood pressure control?", "Oat ingestion reduces systolic and diastolic blood pressure in patients with mild or borderline hypertension: a pilot trial.", "Rye bread decreases serum total and LDL cholesterol in men with moderately elevated serum cholesterol.", "Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults.", "Effects on serum lipids of adding instant oats to usual American diets." ]

[ "This randomized, controlled trial of cholesterol lowering by an oat bran cereal containing beta glucan vs a corn cereal without soluble fiber in Hispanic Americans was conducted for 11 weeks. One-hundred fifty-two men and women, ages 30 to 70 years, with baseline low-density lipoprotein cholesterol (LDL-C) levels between 120 and 190 mg/dL and triglycerides <400 mg/dL were included. After eating a National Cholesterol Education Program Step 1 diet for 5 weeks, subjects were randomly assigned to the corn or the oat cereal for the next 6 weeks. The daily dose of beta glucan was 3 g. Consumption of oat cereal was associated with a reduction in plasma levels of both total cholesterol (-10.9+/-21.6 mg/dL; -4.5%) and LDL-C (-9.4+/-20.3 mg/dL; -5.3%). Consumption of corn cereal did not affect either total cholesterol (+1.2+/-18.3 mg/dL; 1.1%) or LDL-C (+1.2+/-17.5 mg/dL; 2.2%). Differences between the effects of the two cereals on total cholesterol and LDL-C were significant, P =.0003 and P =.0007, respectively.", "Oat cereals rich in the water-soluble fiber beta-glucan have been studied as a dietary therapy for hypercholesterolemia. To determine the hypocholesterolemic response of beta-glucan in the diet, 156 adults with low-density lipoprotein cholesterol (LDL-C) levels above 4.14 mmol/L (160 mg/dL) or between 3.37 and 4.14 mmol/L (130 and 160 mg/dL) with multiple risk factors were randomized to one of seven groups. Six groups received either oatmeal or oat bran at doses (dry weight) of 28 g (1 oz), 56 g (2 oz), and 84 g (3 oz). A seventh group received 28 g of farina (beta-glucan control). At week 6 of treatment, significant differences were found for both total cholesterol and LDL-C levels among the farina control and the treatment groups who were receiving 84 g of oatmeal, 56 g of oat bran, and 84 g of oat bran, with decreases in LDL-C levels of 10.1%, 15.9%, and 11.5%, respectively. Fifty-six grams of oat bran resulted in significantly greater reductions in LDL-C levels than 56 g of oatmeal. Nutrient analysis shows no difference in dietary fat content between these treatment groups; therefore, the higher beta-glucan content of oat bran most likely explains the significantly greater LDL-C reductions. A dose-dependent reduction in LDL-C levels with oat cereals supports the independent hypocholesterolemic effects of beta-glucan.", "The purpose of this study was to confirm and extend previous findings that serum cholesterol response to a fat-modified diet is enhanced by oat fiber. Participants (n = 236) were recruited from the Continental Illinois National Bank in Chicago. Data including weight, serum lipid level, lipoproteins, and 3-day food records were collected at baseline and every 4 weeks for 12 weeks. All participants were instructed to follow the fat-modified (Phase II) diet recommended by the American Heart Association (AHA). After 4 weeks, participants were randomly assigned to one of two groups. While both groups continued to follow the AHA diet, Group 1 was instructed to include 2 oz (56 g, dry wt) of oatmeal, isocalorically substituted for other carbohydrate foods. Group 2 served as the control and consumed no oat products throughout the study. Serum cholesterol values at baseline and after 4 weeks of the AHA diet were similar for both groups (203.9 and 193.0 mg/dl for Group 1 and 205.3 and 194.5 mg/dl for Group 2). After 4 weeks of oatmeal intervention, mean group differences were -6.8 and -2.1 mg/dl (P = 0.008 one-tailed t test) for Groups 1 and 2, respectively. Following an additional 4 weeks of oatmeal intervention, the Group 1 mean cholesterol increased slightly (0.9 mg/dl), while the Group 2 level decreased slightly (-0.7 mg/dl). Overall serum cholesterol responses for the two groups from Visit 2 to Visit 4 were -6.0 and -2.8 mg/dl for Groups 1 and 2, respectively (P = 0.074, one tail). Changes in weight were small and nonsignificant. Subgroup analyses revealed greater reductions in serum cholesterol among participants with the highest baseline serum cholesterol (-8.0 mg/dl vs -1.7 mg/dl for Subgroups 1 and 2, respectively). These data support previous findings that inclusion of oatmeal in a fat-modified diet is helpful in lowering serum cholesterol, particularly for individuals with elevated serum cholesterol levels.", "Our study compared 2 whole grain oat-based cereals with 2 refined grain wheat-based cereals to determine their effects on the need for antihypertensive medications in people with high blood pressure (BP).\n This 12-week, randomized controlled parallel-group trial with = 6 weeks of voluntary follow-up was designed to investigate the antihypertensive effects of oats. After 4 weeks of baseline feeding, medication dose was maintained or reduced by half or completely throughout the middle 4 weeks of the study. In the final 4 weeks, participants continued cereal consumption; medication was adjusted according to the protocol.\n Men and women (n = 88) being treated for hypertension with a mean baseline BP below 160/100.\n Primary study outcomes included change in SBP and DBP as well as antihypertensive medication reduction. Secondary measures included blood lipid, fasting glucose, and insulin levels and side effects related to elevated BP and increased dietary fiber intake.\n Seventy-three percent of participants in the oats group versus 42% in the control group were able to stop or reduce their medication by half. Treatment group participants whose medication was not reduced had substantial decreases in BP. The oats group experienced a 24.2-mg/dL reduction in total cholesterol levels, a 16.2-mg/dL decrease in low-density lipoprotein cholesterol levels, and a 15.03-mg/dL drop in plasma glucose levels vs controls.\n Results suggest that a diet containing soluble fiber-rich whole oats can significantly reduce the need for antihypertensive medication and improve BP control. Considering the lipid and glucose improvements as well, increased consumption of whole oats may significantly reduce cardiovascular disease risk.", "We assessed the short-term antihypertensive effects of soluble fiber-rich whole oat cereals when added to a standard American diet. In addition, multiple assessments of insulin sensitivity were conducted.\n This was a randomized, controlled, parallel-group pilot study designed to compare an oat cereal group (standardized to 5.52 g/day beta-glucan) to a low-fiber cereal control group (less than 1.0 g/day total fiber) over 6 weeks.\n A total of 18 hypertensive and hyperinsulinemic (= 10 U/mL or more) men and women completed the trial.\n Primary study outcomes were changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Secondary outcomes included blood lipid, fasting glucose, and insulin levels and side effects related to elevated blood pressure and increased dietary fiber intake.\n The oat cereal group experienced a 7.5 mm Hg reduction in SBP (P &lt.01) and a 5.5 mm Hg reduction in DBP (P &lt.02), while there was virtually no change in either SBP or DBP in the control group. In the oat cereal group, a trend was observed for a lower total insulin response to a glucose load, suggesting improved insulin sensitivity. However, this could not be confirmed using estimates from the Bergman Minimal Model, perhaps because of our small sample size. The oats group experienced a significant reduction in both total cholesterol (9%) and low-density lipoprotein cholesterol (14%).\n The addition of oat cereals to the normal diet of patients with hypertension significantly reduces both SBP and DBP. Soluble fiber-rich whole oats may be an effective dietary therapy in the prevention and adjunct treatment of hypertension.", "The objective of this study was to determine the hypocholesterolemic effects of whole meal rye and white wheat breads in healthy humans with elevated serum cholesterol concentrations, and the changes in plasma glucose and insulin concentrations during rye and wheat bread periods. The subjects were 18 men and 22 women with baseline serum cholesterol concentration of 6.4+/-0.2 mmol/L. The study design was a 2x4-wk crossover trial during which each subject randomly consumed rye and wheat breads (20% of daily energy) as part of their usual diet for 4 wk. The bread periods were separated by a 4-wk washout period. Blood samples (after fasting) were collected on two consecutive days at the beginning and end of the bread periods. Serum total cholesterol decreased by 8% (P = 0.002) in men but was not significantly altered in women during the rye bread period. The wheat bread period did not affect any of the variables studied. Analysis of the serum lipids in tertiles of rye bread consumption confirmed the reduction in total cholesterol (P = 0.048) in men and revealed the reduction in LDL cholesterol (P = 0.032); both were dependent on the amount of rye bread consumed (-2, -14 and -10% in total cholesterol and 0, -12 and -12% in LDL cholesterol). Neither rye nor wheat bread influenced the concentrations of glucose and insulin. In conclusion, rye bread is effective in reducing serum total and LDL cholesterol concentrations in men with elevated serum cholesterol. Good compliance with consuming a relatively large amount of rye bread in the usual diet indicates that rye bread offers a practical dietary means of reducing serum cholesterol in men.", "Epidemiologic studies have found whole-grain intake to be inversely associated with the risk of type 2 diabetes and heart disease.\n We tested the hypothesis that whole-grain consumption improves insulin sensitivity in overweight and obese adults.\n This controlled experiment compared insulin sensitivity between diets (55% carbohydrate, 30% fat) including 6-10 servings/d of breakfast cereal, bread, rice, pasta, muffins, cookies, and snacks of either whole or refined grains. Total energy needs were estimated to maintain body weight. Eleven overweight or obese [body mass index (in kg/m(2)): 27-36] hyperinsulinemic adults aged 25-56 y participated in a randomized crossover design. At the end of each 6-wk diet period, the subjects consumed 355 mL (12 oz) of a liquid mixed meal, and blood samples were taken over 2 h. The next day a euglycemic hyperinsulinemic clamp test was administered.\n Fasting insulin was 10% lower during consumption of the whole-grain than during consumption of the refined-grain diet (mean difference: -15 +/- 5.5 pmol/L; P = 0.03). After the whole-grain diet, the area under the 2-h insulin curve tended to be lower (-8832 pmol.min/L; 95% CI: -18720, 1062) than after the refined-grain diet. The rate of glucose infusion during the final 30 min of the clamp test was higher after the whole-grain diet (0.07 x 10(-4) mmol.kg(-1).min(-1) per pmol/L; 95% CI: 0.003 x 10(-4), 0.144 x 10(-4)).\n Insulin sensitivity may be an important mechanism whereby whole-grain foods reduce the risk of type 2 diabetes and heart disease.", "This study was designed as a test of the serum lipid response and dietary adaptation to recommended daily inclusion of instant oats in an otherwise regular diet. Hypercholesterolemic adults were randomly assigned to a control or intervention group. Participants in the intervention group were given packages of instant oats and requested to eat two servings per day (approximately two ounces dry weight), substituting the oats for other carbohydrate foods in order to maintain baseline calorie intake and keep weight stable. Serum lipids were measured in blood collected by venipuncture at baseline, four weeks, and eight weeks. Baseline mean total cholesterol (TC) levels were 6.56 mmol/L and 6.39 mmol/L for intervention and control groups, respectively. After eight weeks, mean serum total cholesterol of the intervention group was lower by -0.40 mmol/L, and mean net difference in TC between the two groups was 0.32 mmol/L (95% CI: 0.09, 0.54). Low-density lipoprotein-cholesterol was similarly reduced with mean net difference of 0.25 mmol/L (95% CI: 0.02, 0.48) between the two groups. Mean soluble fiber intake increased along with slight self-imposed reductions in mean total fat, saturated fat, and dietary cholesterol intake in the intervention group. Neither group changed mean body weight. Daily inclusion of two ounces of oats appeared to facilitate reduction of serum total cholesterol and LDL-C in these hyperlipidemic individuals." ]

[ "690583", "8732321", "2179650", "6140351", "7176734", "7496238", "3540329", "6822483", "10320115", "8046193", "10840264" ]

[ "Recognition of depression by family medicine residents: the impact of screening.", "Computerized assessment of common mental disorders in primary care: effect on clinical outcome.", "Improving physicians' recognition and treatment of depression in general medical care. Results from a randomized clinical trial.", "The usefulness of screening for mental illness.", "Screening of depression in relationship to subsequent patient and physician behavior.", "Twelve month outcome of depression in general practice: does detection or disclosure make a difference?", "Detection and management of mental health problems of older patients by primary care providers.", "Recognition and treatment of depression in a family medicine practice.", "Case-finding for depression in primary care: a randomized trial.", "Improving treatment of late life depression in primary care: a randomized clinical trial.", "Randomized trial of case-finding for depression in elderly primary care patients." ]

[ "Psychiatric problems are often encountered in general medical settings, yet physicians frequently fail to identify such problems. Validated questionnaires assessing psychiatric symptoms have been shown to be more sensitive than physicians in detecting cases of psychiatric morbidity. This study deals with depression, the psychiatric problem most frequently seen in primary care settings. A self-administered depression questionnaire was used to alert residents to possible cases of depression. Relay of information from the questionnaire significantly increased resident recognition of depression.", "A randomized controlled trial was conducted to examine the clinical effectiveness of providing general practitioners (GPs) with the results of a self-administered computerized assessment of common mental disorders.\n Attenders at a general practice in a deprived inner city area of South London were identified using case finding questionnaires. Six hundred and eighty-one subjects were randomly allocated to three groups which differed in the information provided to the GP: 1) no additional information was given to the GP; 2) the results of the 12 item General Health Questionnaire (GHQ) were given to the GP (the GHQ is a paper and pencil questionnaire that assesses common mental disorders); 3) the results of a self-administered computerized assessment (PROQSY) of common mental disorders were provided for the GP.\n Clinical outcome was assessed using the 12-item GHQ. Consultations with the GP, prescriptions and referrals within and outside the practice were also recorded. The group in whom the GP received the results of the computerized assessment showed a modest clinical improvement, relative to the other two groups after 6 weeks. There was no difference in clinical outcome between the groups at 6 months. There appeared to be no increase in consultations or prescriptions in the computerized assessment group.\n Self-administered computerized assessments for psychiatric disorder have potential as a means of improving the clinical outcome of patients in primary care. It is likely that the effectiveness of the approach would be greatly increased by linking the results of computerized assessments to clinical practice guidelines, tailored to the individual patient by means of computerized technology.", "A randomized clinical trial was performed to assess whether the results of a depression screening instrument, when provided to physicians, could influence their recognition and treatment of depression in a primary care setting. The intervention consisted of randomly informing or not informing physicians of the depression status of 100 patients who screened positively for depression on both the Zung Self-rating Depression Scale (SDS) and a DSM-III screen. For 12 months patients were followed to assess depression status, and medical records were audited to assess depression recognition and treatment. Results show that feedback to physicians of SDS scores of previously unrecognized depressed patients makes a significant difference in greater recognition (56.2% vs. 34.6%) and treatment (56.2% vs. 42.3%) of depression over the 12-month study period. This was especially true for patients with high somatic (P less than 0.05) or low psychologic symptoms of depression (P less than 0.05). These results suggest that routine use of a depression screening instrument can improve physician recognition of depression, with increased initiation of treatment.", "The study assessed the effect of screening for mental disorder by means of the General Health Questionnaire (GHQ) on the rate of detection of mental disorder by fourteen physicians in a primary-care clinic. After completing the GHQ, patients were randomised into control (722 patients) and experimental (730 patients) groups. GHQ results of the experimental group were made available to the physicians; those of the control group were not. Sociodemographic factors influenced the physicians' rate of diagnosis of mental disorders (rates were lower for men, students, and patients with at least a partial college education than in subjects who had a low income, less than 7 years of school, or were widowed) but there was no difference between control and experimental groups (16.8% vs 16.0%). Among patients with a prior diagnosis of a mental disorder, twice as many were found to have mental disorders by the physicians as by the GHQ (70% vs 33%).", "When internal medicine clinic patients were prescreened for depression and this information was fed back to their physicians, significant effects could be noted on the medical records. On the initial visit, prescreening and previsit feedback about depression increased its notation in the medical record by three times, and among depressed patients, resulted in significantly fewer laboratory tests being orders (X = 2.85 vs. 8.12 for depressed patients with feedback after). During the following year, record notations about depression were more likely to be made for those depressed patients that initially were in the \"feedback before\" group. These patients also saw twice as many providers, made three times as many visits, had three times as any tests ordered, and twice as many medications prescribed as those depressed patients in the \"feedback after\" group. These findings demonstrate that simple prescreening and feedback techniques may have significant and persistent influences on several dimensions of patient and physician behavior.", "To assess the extent to which the outcome of depression among primary care attenders may be affected by medical diagnosis or by feedback of questionnaire results in unrecognised cases.\n Prospective 12 month study including a randomised controlled trial of the effects of disclosure, with data on depression status and clinical management collected by questionnaire and interview.\n Two group practices in north Liverpool.\n 1099/1444 (76%) consecutive adult attenders completed the Beck depression inventory, of whom 179 with scores of at least 14 were followed up.\n Disclosure of a random 45% (52/116) of depression scores to general practitioners for subjects whose depression was undetected.\n Depression status estimated by depression score at start of study and at six and 12 months, with subsample validation against ICD-10 criteria.\n Questionnaire response rates were 76% (136/179) at six months and 68% (122/179) at 12 months and were higher for women than men. The median depression score was 19 (interquartile range 15 to 22) initially, decreasing to 16 (11 to 23) at 12 months. The median depression score decreased significantly (two sided test, P = 0.019) in subjects whose depression was unrecognised at the index consultation but increased in those whose depression had been detected by their general practitioners. Disclosure of cases of unrecognised depression to general practitioners had no effect on outcome. Intention to treat was associated with a worse prognosis, although only a minority of subjects received adequate treatment.\n Disclosure of undetected depression did not improve prognosis. A diagnosis of depression in general practice should be considered simply as a marker of its severity.", "Evidence is accruing that older individuals receive little attention for mental health problems and that any attention that is given is most often within the primary care setting. A randomized clinical trial was carried out at a primary care clinic of The Johns Hopkins University, Baltimore, testing the ability of feedback of the results of a screening instrument (the General Health Questionnaire) to increase awareness in clinicians of the emotional and psychological problems of their patients. This report contrasts those aged 65 years and older with younger patients. Detection and management of mental morbidity were lower for older individuals, but the feedback intervention increased the likelihood of attention to these problems. This was not true for younger patients. Detection was significantly higher for older patients when screening data were made available, as was management, although the latter difference was not statistically significant. There was evidence as well that the intervention moved clinicians to greater congruence with their older patients in the perception that current mental health problems existed. These findings have important implications for primary care.", "To test the hypothesis that depression is significantly underdiagnosed in general medical settings, the Zung Self-Rating Depression Scale was administered to 1,086 family medicine outpatients seen during a 12-month period before their initial medical examination. The effects of such screening on clinical recognition and treatment of depression were examined. Of the 1,086 patients, 143 (13.2%) were symptomatically depressed. These patients were randomized into two groups: 102 were identified as clinically depressed to their physician, and the remaining 41 were not (control group). Physicians diagnosed depression in 15% of the control group and in 68% of the identified group. At 4-week follow-up, 64% of the identified patients who were treated with maprotiline (16 of 25) showed improvement; only 28% of the identified patients who were electively not treated improved. Improvement occurred in only 18% of the control group. It appears that the diagnosis of depression is not ordinarily made in family medicine outpatient settings and that self-rating depression scales are useful diagnostic aids, whose regular use is indicated by the high prevalence of depression in general medical populations.", "Depression is a highly prevalent, morbid, and costly illness that is often unrecognized and inadequately treated. Because depression questionnaires have the potential to improve recognition, we evaluated the accuracy and effects on primary care of two case-finding instruments compared to usual care.\n The study was conducted at three university-affiliated and one community-based medical clinics. Consecutive patients were randomly assigned to be asked a single question about mood, to fill out the 20-item Center for Epidemiologic Studies Depression Screen, or to usual care. Within 72 hours, patients were assessed for Diagnostic and Statistical Manual of Mental Disorders Third Revised Edition (DSM-III-R) disorders by an assessor blinded to the screening results. Process of care was assessed using chart audit and administrative databases; patient and physician satisfaction was assessed using Likert scales. At 3 months, depressed patients and a random sample of nondepressed patients were re-assessed for DSM-III-R disorders and symptom counts.\n We approached 1,083 patients, of whom 969 consented to screening and were assigned to the single question (n = 330), 20-item questionnaire (n = 323), or usual care (n = 316). The interview for DSM-III-R diagnosis was completed in 863 (89%) patients; major depression, dysthymia, or minor depression was present in 13%. Both instruments were sensitive, but the 20-item questionnaire was more specific than the single question (75% vs 66%, P = 0.03). The 20-item questionnaire was less likely to be self-administered (54% vs 90%) and took significantly more time to complete (15 vs 248 seconds). Case-finding with the 20-item questionnaire or single question modestly increased depression recognition, 30/77 (39%) compared with 11/38 (29%) in usual care (P = 0.31) but did not affect treatment (45% vs 43%, P = 0.88). Effects on DSM-III-R symptoms were mixed. Recovery from depression was more likely in the case-finding than usual care groups, 32/67 (48%) versus 8/30 (27%, P = 0.03), but the mean improvement in depression symptoms did not differ significantly (1.6 vs 1.5 symptoms, P = 0.21).\n A simple question about depression has similar performance characteristics as a longer 20-item questionnaire and is more feasible because of its brevity. Case-finding leads to a modest increase in recognition rates, but does not have consistently positive effects on patient outcomes.", "Facilitate primary care physicians' compliance with recommended standards of care for late life depression by reducing barriers to recognition and treatment.\n Randomized controlled clinical trial of physician-targeted interventions.\n Academic primary care group practice caring for an urban, medically indigent patient population.\n Patients aged 60 and older who exceeded the threshold on the Centers for Epidemiologic Studies Depression Scale (CES-D) and the Hamilton Depression Rating Scale (HAM-D) and their primary care physicians.\n Physicians of intervention patients were provided with patient-specific treatment recommendations during 3 special visits scheduled specifically to address the patient's symptoms of depression. In general, physicians were encouraged to establish a diagnosis of depression and educate their patient about the diagnosis, discontinue medications that can cause or exacerbate depressive symptoms, initiate antidepressants when appropriate, and consider referral to psychiatry. Guidelines for prescribing antidepressants were provided. Control physicians received no intervention, and control patients received usual care.\n Frequency of recording a depression diagnosis, stopping medications associated with depression, initiating antidepressant medication, and psychiatry referral; mean changes in HAM-D and Sickness Impact Profile (SIP) scores.\n One hundred three physicians and 175 patients were involved in the clinical trial. Physicians of intervention patients were more likely to diagnose depression and prescribe antidepressants (P < 0.01). There were no differences between the groups in the frequency of stopping medications associated with depression or referrals to psychiatry. Medications with the strongest cause and effect relationship to depression were infrequently used in this cohort of patients. Although both groups showed improvement in HAM-D and SIP scores, we were unable to demonstrate significant differences in HAM-D or SIP scores between the 2 groups.\n Intensive screening and feedback of patient-specific treatment recommendations increased the recognition and treatment of late life depression by primary care physicians. However, we were unable to demonstrate significant improvement in depression or disability severity among intervention patients despite the informational support provided to their physicians. Efforts to improve the functional status of these patients may require more integrated interventions and more aggressive attempts to target psychosocial stressors traditionally outside the purview of primary care.", "To determine the effect of case-finding for depression on frequency of depression diagnoses, prescriptions for antidepressant medications, prevalence of depression, and health care utilization during 2 years of follow-up in elderly primary care patients.\n Randomized controlled trial.\n Thirteen primary care medical clinics at the Kaiser Permanente Medical Center, an HMO in Oakland, Calif, were randomly assigned to intervention conditions (7 clinics) or control conditions (6 clinics).\n A total of 2,346 patients aged 65 years or older who were attending appointments at these clinics and completed the 15-item Geriatric Depression Scale (GDS). GDS scores of 6 or more were considered suggestive of depression.\n Primary care physicians in the intervention clinics were notified of their patients' GDS scores. We suggested that participants with severe depressive symptoms (GDS score >/= 11) be referred to the Psychiatry Department and participants with mild to moderate depressive symptoms (GDS score of 6 -10) be evaluated and treated by the primary care physician. Intervention group participants with GDS scores suggestive of depression were also offered a series of organized educational group sessions on coping with depression led by a psychiatric nurse. Primary care physicians in the control clinics were not notified of their patients' GDS scores or advised of the availability of the patient education program (usual care). Participants were followed for 2 years.\n Physician diagnosis of depression, prescriptions for antidepressant medications, prevalence of depression as measured by the GDS at 2-year follow-up, and health care utilization were determined. A total of 331 participants (14%) had GDS scores suggestive of depression (GDS >/= 6) at baseline, including 162 in the intervention group and 169 in the control group. During the 2-year follow-up period, 56 (35%) of the intervention participants and 58 (34%) of the control participants received a physician diagnosis of depression (odds ratio [OR], 1.0; 95% confidence interval [CI], 0.6 to 1.6; P =.96). Prescriptions for antidepressants were received by 59 (36%) of the intervention participants and 72 (43%) of the control participants (OR, 0.8; 95% CI, 0.5 to 1.2; P =.3). Two-year follow-up GDS scores were available for 206 participants (69% of survivors): at that time, 41 (42%) of the 97 intervention participants and 54 (50%) of the 109 control participants had GDS scores suggestive of depression (OR, 0.7; 95% CI, 0.4 to 1.3; P =.3). Comparing participants in the intervention and control groups, there were no significant differences in mean GDS change scores (-2.4 +/- SD 3.7 vs -2.1 SD +/- 3.6; P =.5) at the 2-year follow-up, nor were there significant differences in mean number of clinic visits (1.8 +/- SD 3.1 vs 1.6 +/- SD 2.8; P =.5) or mean number of hospitalizations (1.1 +/- SD 1.6 vs 1.0 +/- SD 1.4; P =.8) during the 2-year period. In participants with initial GDS scores > 11, there was a mean change in GDS score of -5.6 +/- SD 3.9 for intervention participants (n = 13) and -3.4 +/- SD 4.5 for control participants (n = 21). Adjusting for differences in baseline characteristics between groups did not affect results.\n We were unable to demonstrate any benefit from case-finding for depression during 2 years of follow-up in elderly primary care patients. Studies are needed to determine whether case-finding combined with more intensive patient education and follow-up will improve outcomes of primary care patients with depression." ]

[ "10489946", "10502591", "10028979", "10391261", "10502592", "11354578" ]

[ "Transmyocardial laser revascularisation compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomised trial. ATLANTIC Investigators. Angina Treatments-Lasers and Normal Therapies in Comparison.", "Transmyocardial revascularization with a carbon dioxide laser in patients with end-stage coronary artery disease.", "Transmyocardial laser revascularisation in patients with refractory angina: a randomised controlled trial.", "Holmium:YAG laser transmyocardial revascularization relieves angina and improves functional status.", "Comparison of transmyocardial revascularization with medical therapy in patients with refractory angina.", "Effects of transmyocardial revascularization on myocardial perfusion and systolic function assessed by nuclear and magnetic resonance imaging methods." ]

[ "Transmyocardial revascularisation (TMR) is an operative treatment for refractory angina pectoris when bypass surgery or percutaneous transluminal angioplasty is not indicated. We did a prospective randomised trial to compare TMR with continued medication.\n We recruited 182 patients from 16 US centres with Canadian Cardiovascular Society Angina (CCSA) score III (38%) or IV (62%), reversible ischaemia, and incomplete response to other therapies. Patients were randomly assigned TMR and continued medication (n=92) or continued medication alone (n=90). Baseline assessments were angina class, exercise tolerance, Seattle angina questionnaire for quality of life, and dipyridamole thallium stress test. We reassessed patients at 3 months, 6 months, and 12 months, with independent masked angina assessment at 12 months.\n At 12 months, total exercise tolerance increased by a median of 65 s in the TMR group compared with a 46 s decrease in the medication-only group (p<0.0001, median difference 111 s). Independent CCSA score was II or lower in 47.8% in the TMR group compared with 14.3% in the medication-only group (p<0.001). Each Seattle angina questionnaire index increased in the TMR group significantly more than in the medication-only group (p<0.001).\n TMR lowered angina scores, increased exercise tolerance time, and improved patients' perceptions of quality of life. This operative treatment provided clinical benefits in patients with no other therapeutic options.", "The construction of subendocardial channels to perfuse ischemic areas of the myocardium has been investigated since the 1950s. We assessed the safety and efficacy of transmyocardial revascularization with a carbon dioxide laser in patients with refractory angina and left ventricular free-wall ischemia that was not amenable to direct coronary revascularization.\n In a prospective, controlled, multicenter trial, we randomly assigned 91 patients to undergo transmyocardial revascularization and 101 patients to receive continued medical treatment. The severity of angina (according to the Canadian Cardiovascular Society [CCS] classification), quality of life, and cardiac perfusion (as assessed by thallium-201 scanning) were evaluated at base line and 3, 6, and 12 months after randomization.\n At 12 months, angina had improved by at least two CCS classes in 72 percent of the patients assigned to transmyocardial revascularization, as compared with 13 percent of the patients assigned to medical treatment who continued medical treatment (P<0.001). Patients in the transmyocardial-revascularization group also had a significantly improved quality of life as compared with the medical-treatment group. Myocardial perfusion improved by 20 percent in the transmyocardial-revascularization group and worsened by 27 percent in the medical-treatment group (P=0.002). In the first year of follow-up, 2 percent of patients assigned to undergo transmyocardial revascularization were hospitalized because of unstable angina, as compared with 69 percent of patients assigned to medical treatment (P<0.001). The perioperative mortality rate associated with transmyocardial revascularization was 3 percent. The rate of survival at 12 months was 85 percent in the transmyocardial-revascularization group and 79 percent in the medical-treatment group (P=0.50).\n In patients with angina refractory to medical treatment and coronary artery disease that precluded coronary-artery bypass surgery or percutaneous transluminal coronary angioplasty, transmyocardial revascularization improved cardiac perfusion and clinical status over a 12-month period.", "Transmyocardial laser revascularisation (TMLR) is used to treat patients with refractory angina due to severe coronary artery disease, not suitable for conventional revascularisation. We aimed in a randomised controlled trial to assess the effectiveness of TMLR compared with medical management.\n 188 patients with refractory angina were randomly assigned TMLR plus normal medication or medical management alone. At 3 months, 6 months, and 12 months after surgery (TMLR) or initial assessment (medical management) we assessed exercise capacity with the treadmill test and the 12 min walk.\n Mean treadmill exercise time, adjusted for baseline values, was 40 s (95% CI -15 to 94) longer in the TMLR group than in the medical-management group at 12 months (p=0.152). Mean 12 min walk distance was 33 m (-7 to 74) further in TMLR patients than medical-management patients (p=0.108) at 12 months. The differences were not significant or clinically important. Perioperative mortality was 5%. Survival at 12 months was 89% (83-96) in the TMLR group and 96% (92-100) in the medical-management group (p=0.14). Canadian Cardiovascular Society score for angina had decreased by at least two classes in 25% of TMLR and 4% of medical-management patients at 12 months (p<0.001).\n Our findings show that the adoption of TMLR cannot be advocated. Further research may be appropriate to assess any potential benefit for sicker patients.", "Transmyocardial revascularization (TMR) surgery uses laser channeling of diseased myocardium to treat ischemia and angina. Rigorous prospective randomized studies have been previously unavailable.\n Forty-three patients were randomized to a medication group and 43 to a group scheduled for TMR surgery and medication. All had advanced cardiac ischemia with CCSA class 3 or 4 angina, took at least 2 cardiac medications at maximum doses, and were ineligible for angioplasty or bypass.\n Forty-two of 43 TMR group patients received surgery and were discharged after hospitalizations averaging 3.2 days. Two suffered perioperative MIs, with one death. Four others died within 12 months of surgery, 3 from cardiac events and 1 from pneumonia. Five medical group patients died from cardiac events within 12 months. Three, 6, and 12 month exams showed angina class improvement in TMR patients compared to preoperative values (3.86 +/- 0.05 vs 1.71 +/- 0.2, P < 0.0001), and to controls at 12 months (3.77 +/- 0.07 vs 1.71 +/- 0.2, P < 0.0001). Exercise tolerance improved in TMR patients over preoperative values, and was better than medication group scores after 12 months (490 +/- 17 sec. vs 294 +/- 12 sec., p = 0.0002).\n Holmium:YAG laser channeling of the myocardium improves function and reduces angina in advanced cardiac patients who lack alternative therapeutic options.", "Transmyocardial revascularization involves the creation of channels in the myocardium with a laser to relieve angina. We compared the safety and efficacy of transmyocardial revascularization performed with a holmium laser with those of medical therapy in patients with refractory class IV angina (according to the criteria of the Canadian Cardiovascular Society).\n In a prospective study conducted between March 1996 and July 1998 at 18 centers, 275 patients with medically refractory class IV angina and coronary disease that could not be treated with percutaneous or surgical revascularization were randomly assigned to receive transmyocardial revascularization followed by continued medical therapy (132 patients) or medical therapy alone (143 patients).\n After one year of follow-up, 76 percent of the patients who had undergone transmyocardial revascularization had improvement in angina (a reduction of two or more classes), as compared with 32 percent of the patients who received medical therapy alone (P<0.001). Kaplan-Meier survival estimates at one year (based on an intention-to-treat analysis) were similar for the patients assigned to undergo transmyocardial revascularization and those assigned to receive medical therapy alone (84 percent and 89 percent, respectively; P=0.23). At one year, the patients in the transmyocardial-revascularization group had a significantly higher rate of survival free of cardiac events (54 percent, vs. 31 percent in the medical-therapy group; P<0.001), a significantly higher rate of freedom from treatment failure (73 percent vs. 47 percent, P<0.001), and a significantly higher rate of freedom from cardiac-related rehospitalization (61 percent vs. 33 percent, P<0.001). Exercise tolerance and quality-of-life scores were also significantly higher in the transmyocardial-revascularization group than in the medical-therapy group (exercise tolerance, 5.0 MET [metabolic equivalent] vs. 3.9 MET; P=0.05); quality-of-life score, 21 vs. 12; P=0.003). However, there were no differences in myocardial perfusion between the two groups, as assessed by thallium scanning.\n Patients with refractory angina who underwent transmyocardial revascularization and received continued medical therapy, as compared with similar patients who received medical therapy alone, had a significantly better outcome with respect to improvement in angina, survival free of cardiac events, freedom from treatment failure, and freedom from cardiac-related rehospitalization.", "There is no obvious explanation, except placebo, to the symptomatic effect of transmyocardial laser revascularization (TMR) in patients with refractory angina. Whether TMR improves myocardial perfusion or relieves symptoms without altering cardiac function is not clarified.\n One hundred patients with refractory angina were randomized 1:1 to TMR (CO2 laser) and medical treatment, or medical treatment alone. Technetium 99m (99mTc)-tetrofosmin myocardial perfusion tomography (SPECT), quantitative myocardial perfusion gated SPECT (QGSPECT), technetium 99m (99mTc) multiple gated acquisition radionuclide ventriculografi (MUGA) and cine-magnetic resonance imaging (cine-MRI) were performed at baseline and after 3 and 12 months.\n Following TMR, a slight reduction in left ventricular ejection fraction (LVEF) (p < 0.05) was observed (MUGA and QGSPECT) compared to baseline. Inclusion of incomplete studies (QGSPECT) revealed a significant reduction in LVEF and increase in left ventricular end-diastolic volume (LVEDV) (p < 0.05) compared to a control group. Otherwise, no between-group comparisons showed statistically significant differences.\n TMR did not improve myocardial perfusion, but led to a reduction in LVEF and increase in LVEDV, however not significantly different from the control group." ]

[ "19237734", "15543446", "16186521", "20508185", "17167194", "19841835", "18469735", "19389746", "18988916", "22275463", "19692788", "18358724", "18954289", "16271575", "20581337", "15890990" ]

[ "A randomized controlled trial of gravity-supported, computer-enhanced arm exercise for individuals with severe hemiparesis.", "Stepping over obstacles to improve walking in individuals with poststroke hemiplegia.", "Effect of simulator training on driving after stroke: a randomized controlled trial.", "Effectiveness of virtual reality using Wii gaming technology in stroke rehabilitation: a pilot randomized clinical trial and proof of principle.", "Virtual reality training for stroke rehabilitation.", "Exercises for paretic upper limb after stroke: a combined virtual-reality and telemedicine approach.", "''Playstation eyetoy games'' improve upper extremity-related motor functioning in subacute stroke: a randomized controlled clinical trial.", "A computerized visual perception rehabilitation programme with interactive computer interface using motion tracking technology -- a randomized controlled, single-blinded, pilot clinical trial study.", "Effects of training with a robot-virtual reality system compared with a robot alone on the gait of individuals after stroke.", "Virtual reality in the rehabilitation of the arm after hemiplegic stroke: a randomized controlled pilot study.", "Use of virtual reality to enhance balance and ambulation in chronic stroke: a double-blind, randomized controlled study.", "Virtual reality-based training improves community ambulation in individuals with stroke: a randomized controlled trial.", "An electric scooter simulation program for training the driving skills of stroke patients with mobility problems: a pilot study.", "Cortical reorganization and associated functional motor recovery after virtual reality in patients with chronic stroke: an experimenter-blind preliminary study.", "Motor learning principles for rehabilitation: a pilot randomized controlled study in poststroke patients.", "Virtual reality-induced cortical reorganization and associated locomotor recovery in chronic stroke: an experimenter-blind randomized study." ]

[ "The authors previously developed a passive instrumented arm orthosis (Therapy Wilmington Robotic Exoskeleton [T-WREX]) that enables individuals with hemiparesis to exercise the arm by playing computer games in a gravity-supported environment. The purpose of this study was to compare semiautonomous training with T-WREX and conventional semiautonomous exercises that used a tabletop for gravity support.\n Twenty-eight chronic stroke survivors with moderate/severe hemiparesis were randomly assigned to experimental (T-WREX) or control (tabletop exercise) treatment. A blinded rater assessed arm movement before and after twenty-four 1-hour treatment sessions and at 6-month follow-up. Subjects also rated subjective treatment preferences after a single-session crossover treatment.\n All subjects significantly improved ( P < or = .05) upper extremity motor control (Fugl-Meyer), active reaching range of motion (ROM), and self-reported quality and amount of arm use (Motor Activity Log). Improvements were sustained at 6 months. The T-WREX group maintained gains on the Fugl-Meyer significantly better than controls at 6 months (improvement of 3.6 +/- 3.9 vs 1.5 +/- 2.7 points, mean +/- SD; P = .04). Subjects also reported a preference for T-WREX training.\n Gravity-supported arm exercise, using the T-WREX or tabletop support, can improve arm movement ability after chronic severe hemiparesis with brief one-on-one assistance from a therapist (approximately 4 minutes per session). The 3-dimensional weight support, instant visual movement feedback, and simple virtual reality software provided by T-WREX were associated with modest sustained gains at 6-month follow-up when compared with the conventional approach.", "For this study, we evaluated two training interventions for improving gait parameters in individuals with poststroke hemiplegia using a training methodology that required them to step over objects. Gait velocity, step length, ability to step over obstacles, and walking endurance were compared before and after 2 weeks of training and 2 weeks after cessation of training. Twenty subjects with poststroke hemiplegia completed six intervention sessions in which they were asked to step over either virtual objects while walking on a motorized treadmill or real foam objects on a 10 m walkway. With the virtual object training, if either foot collided with the virtual object, a tone sounded and a vibrotactile stimulus was applied to the colliding foot. All subjects tolerated the training sessions well, and no incidences of falling or undue cardiovascular responses occurred. The virtual obstacle training generated greater improvements in gait velocity compared with real training (20.5% vs. 12.2% improvement) during the fast walk test (p < 0.01). Improvements in gait velocity for both training methods were similar in the self-selected walk test (33.3% vs. 34.7% improvement). Overall, subjects showed clinically meaningful changes in gait velocity, stride length, walking endurance, and obstacle clearance capacity as a result of either training method. These changes persisted for 2 weeks posttraining. The inclusion of enhanced safety and visual augmentation may be responsible for the effectiveness of the virtual object intervention. These results demonstrate preliminary evidence for clinical effectiveness of obstacle training for improving gait velocity poststroke. In addition, these results provide evidence for enhanced clinical performance with virtual obstacle training.", "Neurologically impaired persons seem to benefit from driving-training programs, but there is no convincing evidence to support this notion. The authors therefore investigated the effect of simulator-based training on driving after stroke.\n Eighty-three first-ever subacute stroke patients entered a 5-week 15-hour training program in which they were randomly allocated to either an experimental (simulator-based training) or control (driving-related cognitive tasks) group. Performance in off-road evaluations and an on-road test were used to assess the driving ability of subjects pre- and post-training. Outcome of an official predriving assessment administered 6 to 9 months poststroke was also considered.\n Both groups significantly improved in a visual and many neuropsychological evaluations and in the on-road test after training. There were no significant differences between both groups in improvements from pre- to post-training except in the \"road sign recognition test\" in which the experimental subjects improved more. Significant improvements in the three-class decision (\"fit to drive,\" \"temporarily unfit to drive,\" and \"unfit to drive\") were found in favor of the experimental group post-training. Academic qualification and overall disability together determined subjects that benefited most from the simulator-based driving training. Significantly more experimental subjects (73%) than control subjects (42%) passed the follow-up official predriving assessment and were legally allowed to resume driving.\n Simulator-based driving training improved driving ability, especially for well educated and less disabled stroke patients. However, the findings of the study may have been modified as a result of the large number of dropouts and the possibility of some neurologic recovery unrelated to training.", "Hemiparesis resulting in functional limitation of an upper extremity is common among stroke survivors. Although existing evidence suggests that increasing intensity of stroke rehabilitation therapy results in better motor recovery, limited evidence is available on the efficacy of virtual reality for stroke rehabilitation.\n In this pilot, randomized, single-blinded clinical trial with 2 parallel groups involving stroke patients within 2 months, we compared the feasibility, safety, and efficacy of virtual reality using the Nintendo Wii gaming system (VRWii) versus recreational therapy (playing cards, bingo, or \"Jenga\") among those receiving standard rehabilitation to evaluate arm motor improvement. The primary feasibility outcome was the total time receiving the intervention. The primary safety outcome was the proportion of patients experiencing intervention-related adverse events during the study period. Efficacy, a secondary outcome measure, was evaluated with the Wolf Motor Function Test, Box and Block Test, and Stroke Impact Scale at 4 weeks after intervention.\n Overall, 22 of 110 (20%) of screened patients were randomized. The mean age (range) was 61.3 (41 to 83) years. Two participants dropped out after a training session. The interventions were successfully delivered in 9 of 10 participants in the VRWii and 8 of 10 in the recreational therapy arm. The mean total session time was 388 minutes in the recreational therapy group compared with 364 minutes in the VRWii group (P=0.75). There were no serious adverse events in any group. Relative to the recreational therapy group, participants in the VRWii arm had a significant improvement in mean motor function of 7 seconds (Wolf Motor Function Test, 7.4 seconds; 95% CI, -14.5, -0.2) after adjustment for age, baseline functional status (Wolf Motor Function Test), and stroke severity.\n VRWii gaming technology represents a safe, feasible, and potentially effective alternative to facilitate rehabilitation therapy and promote motor recovery after stroke.", "To evaluate the effectiveness of a 2-D virtual reality (2DVR) programme in the training of people with stroke on how to access and use the station facilities of the Mass Transit Railway (MTR).\n A flat-screen 2DVR based training programme and a corresponding, typical psycho-educational programme with video modelling were developed for comparison through a research design that involved a randomised control group pre-test and post-test.\n Twenty and sixteen subjects respectively received 10 training sessions using the 2DVR strategy and a video-based psycho-educational programme. An additional 22 subjects formed the control group. They were assessed by using a behavioural checklist of MTR skills and a newly validated MTR self-efficacy scale. The subjects of both training groups showed a significant improvement in their knowledge, skills and self-efficacy in using the MTR (p<0.01), whereas, the MTR skills and self-efficacy of the control group remained stable over a four-week interval.\n Though both training programmes were effective in training the patients with stroke, they demonstrated differential improvements in MTR skills and related self-efficacy. Additional studies are recommended to identify the most effective training procedures for maintaining these skills and the best transfer ratio in the training of VR-based community living skills of people with stroke.", "Telerehabilitation enables a remotely controlled programme to be used to treat motor deficits in post-stroke patients. The effects of this telerehabilitation approach were compared with traditional motor rehabilitation methods.\n Randomized single-blind controlled trial.\n A total of 36 patients with mild arm motor impairments due to ischaemic stroke in the region of the middle cerebral artery.\n The experimental treatment was a virtual reality-based system delivered via the Internet, which provided motor tasks to the patients from a remote rehabilitation facility. The control group underwent traditional physical therapy for the upper limb. Both treatments were of 4 weeks duration. All patients were assessed one month prior to therapy, at the commencement and termination of therapies and one month post-therapy, with the Fugl-Meyer Upper Extremity, the ABILHAND and the Ashworth scales.\n Both rehabilitative therapies significantly improved all outcome scores after treatment, but only the Fugl-Meyer Upper Extremity scale showed differences in the comparison between groups.\n Both strategies were effective, but the experimental approach induced better outcomes in motor performance. These results may favour early discharge from hospital sustained by a telerehabilitation programme, with potential beneficial effects on the use of available resources.", "To evaluate the effects of ''Playstation EyeToy Games'' on upper extremity motor recovery and upper extremity-related motor functioning of patients with subacute stroke.\n The authors designed a randomized, controlled, assessor-blinded, 4-week trial, with follow-up at 3 months. A total of 20 hemiparetic inpatients (mean age 61.1 years), all within 12 months post-stroke, received 30 minutes of treatment with ''Playstation EyeToy Games'' per day, consisting of flexion and extension of the paretic shoulder, elbow and wrist as well as abduction of the paretic shoulder or placebo therapy (watching the games for the same duration without physical involvement into the games) in addition to conventional program, 5 days a week, 2-5 hours/day for 4 weeks. Brunnstrom's staging and self-care sub-items of the functional independence measure (FIM) were performed at 0 month (baseline), 4 weeks (post-treatment), and 3 months (follow-up) after the treatment.\n The mean change score (95% confidence interval) of the FIM self-care score (5.5 [2.9-8.0] vs 1.8 [0.1-3.7], P=0.018) showed significantly more improvement in the EyeToy group compared to the control group. No significant differences were found between the groups for the Brunnstrom stages for hand and upper extremity.\n ''Playstation EyeToy Games'' combined with a conventional stroke rehabilitation program have a potential to enhance upper extremity-related motor functioning in subacute stroke patients.", "To assess the effectiveness of a computerized visual perception rehabilitation programme using motion tracking technology for visual perception impairment.\n Randomized controlled, single-blinded, pilot clinical trial study.\n Inpatient rehabilitation hospital.\n Sixteen left hemiplegic patients with visual perceptional impairment.\n Subjects were randomly assigned to receive either (1) participation in a computerized visual perception rehabilitation programme with an interactive patient-computer interface applying motion tracking technology based on the CAMSHIFT algorithm or (2) use of the PSS CogRehab program for three sessions per week, 30 minutes per session for four weeks. There were eight patients in each group.\n Mini-Mental Status Examination, Motor-free Visual Perception Test and Modified Barthel Index were assessed at the beginning and end of the training. A survey was conducted to evaluate the degree of patients' interest using an interest scale.\n After training, the mean (SD) Motor-free Visual Perception Test score increased significantly in both experimental group (from 65.8 (19.5) to 77.8 (28.7)) and control group (from 68.3 (11.4) to 74.1 (14.8)) (P<0.01). Modified Barthel Index score increased significantly in both groups, with the experimental group recording a higher increase. Mean (SD) interest scale score was greater in the experimental group (2.2 (0.8)) than in the control group (1.3 (0.7)) (P<0.01).\n A computerized visual perception rehabilitation programme with interactive computer interface using motion tracking technology could be considered as a treatment option for stroke patients with visual perception impairment.", "Training of the lower extremity (LE) using a robot coupled with virtual environments has shown to transfer to improved overground locomotion. The purpose of this study was to determine whether the transfer of training of LE movements to locomotion was greater using a virtual environment coupled with a robot or with the robot alone.\n A single, blind, randomized clinical trial was conducted. Eighteen individuals poststroke participated in a 4-week training protocol. One group trained with the robot virtual reality (VR) system and the other group trained with the robot alone. Outcome measures were temporal features of gait measured in a laboratory setting and the community.\n Greater changes in velocity and distance walked were demonstrated for the group trained with the robotic device coupled with the VR than training with the robot alone. Similarly, significantly greater improvements in the distance walked and number of steps taken in the community were measured for the group that trained with robot coupled with the VR. These differences were maintained at 3 months' follow-up.\n The study is the first to demonstrate that LE training of individuals with chronic hemiparesis using a robotic device coupled with VR improved walking ability in the laboratory and the community better than robot training alone.", "To assess the feasibility of a trial to investigate the effectiveness of virtual reality-mediated therapy compared to conventional physiotherapy in the motor rehabilitation of the arm following stroke, and to provide data for a power analysis to determine numbers for a future main trial.\n Pilot randomized controlled trial.\n Clinical research facility.\n Eighteen people with a first stroke, 10 males and 8 females, 7 right and 2 left side most affected. Mean time since stroke 10.8 months.\n Participants were randomized to a virtual reality group or a conventional arm therapy group for nine sessions over three weeks.\n The upper limb Motricity Index and the Action Research Arm Test were completed at baseline, post intervention and six weeks follow-up.\n Outcome data were obtained from 95% of participants at the end of treatment and at follow-up: one participant withdrew. Compliance was high; only two people reported side-effects from virtual reality exposure. Both groups demonstrated small (7-8 points on upper limb Motricity Index and 4 points on the Action Research Arm Test), but non-significant, changes to their arm impairment and activity levels.\n A randomized controlled trial of virtual reality-mediated therapy comparable to conventional therapy would be feasible, with some suggested improvements in recruitment and outcome measures. Seventy-eight participants (39 per group) would be required for a main trial.", "To examine an additive effect of virtual reality on balance and gait function in patients with chronic hemiparetic stroke.\n Twenty-four adults with hemiparetic stroke were randomly assigned to either an experimental group (n = 12) or a control group. Both groups underwent conventional physical therapy, 40 mins a day, 4 days a week for 4 wks. The experimental group received an additional 30 mins of virtual reality therapy each session. Balance performance was determined by the Balance Performance Monitor and Berg Balance Scale tests. Gait performance was determined by the 10-m walking test and Modified Motor Assessment Scale, and spatiotemporal parameters were obtained using GAITRite. Analysis of variance and correlation statistics were performed at P < 0.05.\n In the balance test, the experimental group had improved Berg Balance Scale scores, balance and dynamic balance angles (ability to control weight shifting) compared with the controls (P < 0.05). In the gait performance test, the experimental group showed significant improvements in velocity, Modified Motor Assessment Scale scores, cadence, step time, step length, and stride length (P < 0.05). Improvement in dynamic balance angles was correlated with velocity and cadence (P < 0.01).\n This study demonstrates that virtual reality has an augmented effect on balance and associated locomotor recovery in adults with hemiparetic stroke when added to conventional therapy.", "This is a single blind randomized controlled trial to examine the effect of virtual reality-based training on the community ambulation in individuals with stroke. Twenty subjects with stroke were assigned randomly to either the control group (n=9) or the experimental group (n=11). Subjects in the control group received the treadmill training. Subjects in the experimental group underwent the virtual reality-based treadmill training. Walking speed, community walking time, walking ability questionnaire (WAQ), and activities-specific balance confidence (ABC) scale were evaluated. Subjects in the experimental group improved significantly in walking speed, community walking time, and WAQ score at posttraining and 1-month follow-up periods. Their ABC score also significantly increased at posttraining but did not maintain at follow-up period. Regarding the between-group comparisons, the experimental group improved significantly more than control group in walking speed (P=0.03) and community walking time (P=0.04) at posttraining period and in WAQ score (P=0.03) at follow-up period. Our results support the perceived benefits of gait training programs that incorporate virtual reality to augment the community ambulation of individuals with stroke.", "This paper describes an electric scooter simulation program and a first evaluation study in which we explored if it is possible to train the driving skills of future users of electric mobility scooters by means of an electric scooter simulation program in addition to conventional electric scooter training. Within this explorative study,10 stroke survivors were randomly assigned to either the control (n=5) or the electric scooter simulation intervention group (n=5). Participants were assessed twice on the functional evaluating rating scale. During the followup measurement, subjective experiences regarding both forms of electric scooter training were elicited by a questionnaire. After a training period of 5 weeks, both groups improved on the Functional Evaluation Rating Scale. It can be concluded that the patients with stroke were satisfied with the electric scooter simulation training.", "To investigate the effects of virtual reality (VR) on cortical reorganization and motor recovery.\n Nonparametric pre- and posttest design with experimenter blinded.\n University medical center.\n Five patients with hemiparesis (age, 59.8+/-3.4y) were recruited.\n Five patients received VR for 60 minutes a day, 5 times a week for 4 weeks. VR was designed to provide a virtual rehabilitation scene where the intensity of practice and sensory feedback could be systematically manipulated to provide the most appropriate, individualized motor retraining program.\n Cortical activation and associated motor recovery were measured before and after VR using functional magnetic resonance imaging and standardized motor tests, respectively. Nonparametric tests were used at P less than .05.\n Prior to VR, the bilateral primary sensorimotor cortices (SM1s), contralesional premotor cortex, and contralesional or ipsilesional supplementary motor area were activated. After VR, the altered activations disappeared and predominantly the ipsilesional SM1 was activated (P<.05). Motor function was improved (P<.05).\n This is a novel demonstration of VR-induced neuroplastic changes and associated motor recovery in chronic stroke.", "Six months after a stroke, the hemiplegic arm often remains compromised. More innovative approaches to motor rehabilitation are needed.\n The authors compared a motor learning-based approach in a virtual environment with more conventional upper extremity therapy in a pilot trial.\n This prospective, single-blinded, randomized controlled trial compared reinforced feedback in a virtual environment (RFVE; n = 27) with a control intervention (n = 20) of progressive therapy for the affected upper extremity. Both treatments were provided for 4 weeks, 5 days per week, with 1-hour treatment sessions daily. The primary outcomes were the Fugl-Meyer Upper Extremity (F-M UE) and Functional Independence Measure (FIM) scores. Kinematic outcomes included mean duration (MD), mean linear velocity (MLV), and number of submovements to measure the motor performance. Analyses of the primary outcomes were performed per protocol and by intention to treat.\n F-M UE scores improved significantly in the RFVE group compared with the conventional therapy group (\"intention to treat\" = 5.10 points, P = .004; ANCOVA = 4.26 points, P < .01). Several of the kinematic parameters improved in the RFVE group (MD, P < .01; MLV, P < .01). FIM improvements did not differ.\n Both rehabilitation therapies improved arm motor performance and functional activity, but the RFVE therapy induced more robust results in patients exposed to late rehabilitation treatment.", "Virtual reality (VR) is a new promising computer-assisted technology to promote motor recovery in stroke patients. VR-induced neuroplasticity supporting locomotor recovery is not known. We investigated the effects of VR intervention on cortical reorganization and associated locomotor recovery in stroke patients.\n Ten chronic stroke patients were assigned randomly to either the control group or the VR group. VR was designed to provide interactive real-life practice environments in which practice parameters can be individualized to optimize motor relearning. Laterality index (LI) in the regions of interests (ROIs) and locomotor recovery were measured before and after VR using functional MRI (fMRI) and standardized locomotor tests, respectively. The t test and nonparametric test were performed to compare the mean differences at P<0.05.\n There was a significant difference in the interval change in the LI score for the primary sensorimotor cortex (SMC) between the groups (P<0.05), indicating that VR practice produced a greater increase in LI for the control group. However, the interval changes in the other ROIs were not significantly different (P>0.05). Motor function was significantly improved after VR (P<0.05).\n Our novel findings suggest that VR could induce cortical reorganization from aberrant ipsilateral to contralateral SMC activation. This enhanced cortical reorganization might play an important role in recovery of locomotor function in patients with chronic stroke. This is the first fMRI study in the literature that provides evidence for neuroplasticity and associated locomotor recovery after VR." ]

[ "16507032", "15966958", "9242847", "15966959", "11157431", "8884589" ]

[ "Bereaved adults with intellectual disabilities: a combined randomized controlled trial and qualitative study of two community-based interventions.", "Randomized controlled trial of assertive community treatment in intellectual disability: the TACTILD study.", "Hospital vs. outreach treatment of patients with mental retardation and psychiatric disorders: a controlled study.", "An exploratory study of assertive community treatment for people with intellectual disability and psychiatric disorders: conceptual, clinical, and service issues.", "Intellectual functioning and outcome of patients with severe psychotic illness randomised to intensive case management. Report from the UK700 trial.", "Challenging behaviour: the effectiveness of specialist support teams." ]

[ "Bereaved adults with intellectual disabilities are known to experience prolonged and atypical grief which is often unrecognized. The aim of this project was to find an effective way to improve mental health and behavioural outcomes.\n Subjects were randomized to two different therapeutic interventions: traditional counselling by volunteer bereavement counsellors, and an integrated intervention delivered by carers which offered bereavement specific support. Qualitative and quantitative methods were used to determine their effectiveness and efficacy.\n The counselling intervention resulted in measurable gains both clinically and in terms of quality of life; the second intervention proved impracticable in most settings and no improvement in mental health or behaviour resulted.\n Despite small numbers, the quantitative findings were highly significant, were supported by the qualitative data, and were of practical relevance to primary care practitioners and specialist mental health and intellectual disability staff.", "There has been a policy shift away from hospital to community in the services of all those with psychiatric disorders, including those with intellectual disability (ID), in the last 50 years. This has been accompanied recently by the growth of assertive outreach services, but these have not been evaluated in ID services.\n In a randomized controlled trial we compared assertive outreach with 'standard' community care, using global assessment of function (GAF) as the primary outcome measure, and burden and quality of life as secondary measures.\n We recruited 30 patients, considerably less than expected; no significant differences were found between the primary and secondary outcomes in the two groups. The differences were so small that a Type II error was unlikely.\n Reasons for this lack of specific efficacy of the assertive approach are discussed and it is suggested that there is a blurring of the differences between standard and assertive approaches in practice.", "The aim of this study was to investigate the effectiveness of specialized hospital treatment vs. outreach treatment of patients with mental retardation and serious mental illness. A total of 50 patients were randomly assigned to either the hospital treatment (n = 25) or the outreach treatment group (n = 25). The outcome measures included psychiatric symptoms, family burden, costs and hospital admissions. At most observation points (up to 28 weeks) and at all endpoints the two groups were equivalent with regard to psychiatric symptoms. The burden on carers did not increase significantly during the outreach treatment. Treatment costs were lower for the outreach treatment. Of the 25 patients who received outreach treatment, four had to be admitted to the specialized hospital. Aggressive behaviour, social competence and number of previous psychiatric hospitalizations were found to be predictors of treatment outcome. It is concluded that outreach treatment represents an effective and efficient alternative to hospital treatment for patients with mental retardation and psychiatric disorders.", "Assertive community treatment (ACT) has been applied to a number of disorders in the adult population, such as schizophrenia, with some degree of success; its use in the treatment of people with intellectual disability (ID) and mental illness has received little attention. Despite the high costs of ID in health and social care, there has been very little evidence-based practice for people with ID and mental illness, and it remains a neglected area of research. Aims The aims of this study were an exploratory comparison of the effectiveness of an ACT model for the treatment of mental illness in people with ID (ACT-ID) with a standard community treatment (SCT-ID) approach.\n A Randomized controlled trial design was adopted and allocation was made by stratified randomization by an independent statistician. The prognostic factors used in the randomization were gender and psychiatric diagnosis (psychosis vs. affective). Service users were randomly allocated to either ACT-ID or SCT-ID.\n There were no statistically significant differences between ACT-ID and SCT-ID in terms of the level of unmet needs, carer burden, functioning and quality of life, but borderline evidence of a difference between treatment groups in quality of life in favour of SCT-ID. Both SCT-ID and ACT-ID groups decreased level of unmet needs and carer burden, and increased functioning. SCT-ID also led to a small increase in quality of life.", "Little research has been carried out on the benefits of intensive case management (ICM) for people with borderline IQ and severe mental illness.\n To compare outcome and costs of care of patients with severe psychotic illness with borderline IQ to patients of normal IQ and to assess whether ICM is more beneficial for the former than for the latter.\n The study utilises data from the UK700 multi-centre randomised controlled trial of case management. The main outcome measure was the number of days spent in hospital for psychiatric reasons. Secondary outcomes were costs of care and clinical outcome.\n ICM was significantly more beneficial for borderline-IQ patients than those of normal IQ in terms of reductions in days spent in hospital, hospital admissions, total costs and needs and increased satisfaction.\n ICM appears to be a cost-effective strategy for a subgroup of patients with severe psychosis with cognitive deficits.", "Two specialist community services for people with learning disabilities and challenging behaviour were evaluated over approximately 3 years. Intervention effectiveness was assessed with respect to changes in subjects' skills, challenging behaviours, mental health and quality of life, and to changes in staff morale. Subjects assessed as having challenging behaviour but not referred for specialist input were also studied. Comparison of changes in referred and non-referred samples over time showed minor differences only, indicating little intervention effect and demonstrating stability in the comparison sample. Analysis of the two services separately yielded different results. Positive client change was evident with respect to one service, whilst little change was noted with respect to the other. There was little evidence to suggest that either service had any effect on staff morale. Differences between the two services in terms of structure, staffing characteristics and operational policies are discussed as possible factors in the differential results obtained. A major issue raised by the study concerns the quality of settings from which the subjects were referred for specialist support. This is discussed as a factor which may limit the effectiveness of specialist input." ]

[ "11547053", "10569535", "20346030", "16527562", "10646679", "12508134", "19815264" ]

[ "Prospective randomized trial comparing shock wave lithotripsy and ureteroscopy for management of distal ureteral calculi.", "Extracorporeal shock wave lithotripsy versus ureteroscopy for distal ureteral calculi: a prospective randomized study.", "Extracorporeal shockwave lithotripsy vs ureteroscopy as first-line therapy for patients with single, distal ureteric stones: a prospective randomized study.", "Prospective randomized trial comparing shock wave lithotripsy and ureteroscopic lithotripsy for management of large upper third ureteral stones.", "Treatment for extended-mid and distal ureteral stones: SWL or ureteroscopy? Results of a multicenter study.", "Extracorporeal shock-wave versus pneumatic ureteroscopic lithotripsy in treatment of lower ureteral calculi.", "A prospective randomized study comparing shock wave lithotripsy and semirigid ureteroscopy for the management of proximal ureteral calculi." ]

[ "We compared the efficacy of shock wave lithotripsy and ureteroscopy for treatment of distal ureteral calculi.\n A total of 64 patients with solitary, radiopaque distal ureteral calculi 15 mm. or less in largest diameter were randomized to treatment with shock wave lithotripsy (32) using an HM3 lithotriptor (Dornier MedTech, Kennesaw, Georgia) or ureteroscopy (32). Patient and stone characteristics, treatment parameters, clinical outcomes, patient satisfaction and cost were assessed for each group.\n The 2 groups were comparable in regard to patient age, sex, body mass index, stone size, degree of hydronephrosis and time to treatment. Procedural and operating room times were statistically significantly shorter for the shock wave lithotripsy compared to the ureteroscopy group (34 and 72 versus 65 and 97 minutes, respectively). In addition, 94% of patients who underwent shock wave lithotripsy versus 75% who underwent ureteroscopy were discharged home the day of procedure. At a mean followup of 21 and 24 days for shock wave lithotripsy and ureteroscopy, respectively, 91% of patients in each group had undergone imaging with a plain abdominal radiograph, and all studies showed resolution of the target stone. Minor complications occurred in 9% and 25% of the shock wave lithotripsy and ureteroscopy groups, respectively (p value was not significant). No ureteral perforation or stricture occurred in the ureteroscopy group. Postoperative flank pain and dysuria were more severe in the ureteroscopy than shock wave lithotripsy group, although the differences were not statistically significant. Patient satisfaction was high, including 94% for shock wave lithotripsy and 87% for ureteroscopy (p value not significant). Cost favored ureteroscopy by $1,255 if outpatient treatment for both modalities was assumed.\n Ureteroscopy and shock wave lithotripsy were associated with high success and low complication rates. However, shock wave lithotripsy required significantly less operating time, was more often performed on an outpatient basis, and showed a trend towards less flank pain and dysuria, fewer complications and quicker convalescence. Patient satisfaction was uniformly high in both groups. Although ureteroscopy and shock wave lithotripsy are highly effective for treatment of distal ureteral stones, we believe that HM3 shock wave lithotripsy, albeit slightly more costly, is preferable to manipulation with ureteroscopy since it is equally efficacious, more efficient and less morbid.", "We performed a prospective randomized study to determine appropriate first line treatment for distal ureteral stones.\n Between January 1996 and October 1997, 80 patients with distal ureteral stones (40 smaller than 5 mm. and 40 larger than 5 mm.) were randomized and treated with extracorporeal shock wave lithotripsy or ureteroscopy with a 9.5 or 6.5F semirigid ureteroscope.\n Ureteroscopy was significantly better in terms of operative time, fluoroscopy time and time to achieve a stone-free state. The smaller the stones, the greater the difference between the 2 treatment modalities.\n For distal ureteral stones we recommend ureteroscopy as first line treatment.", "To compare extracorporeal shockwave lithotripsy (ESWL) and ureteroscopy (URS) as first-line treatments for patients with distal ureteric stones.\n In all, 273 patients with single, monolateral, radiopaque, distal ureteric stones of 0.5-1.5 cm were enrolled in a prospective randomized trial. Patients were randomized to undergo ESWL (137) or URS (136). The electromagnetic Modulith SLX lithotripter (Storz Medical, Switzerland) was used for ESWL and a semi-rigid ureteroscope was used for URS. Patients in both groups were compared for overall stone-free rates (SFRs), re-treatment rates, need for auxiliary procedures and complication rates. A subgroup analysis was performed in both groups according to stone size of ≤1 cm and >1 cm.\n Patients in the ESWL group achieved a 92.70% overall SFR with a 44.88% re-treatment rate and an 11.02% auxiliary procedure rate. Complications occurred in 15.32% of patients treated with ESWL. Patients in the URS group achieved a 94.85% overall SFR with a re-treatment rate of 7.75% and an auxiliary procedure rate of 18.60%. Complications occurred in 19.11% of patients treated with URS. In the ESWL group, the need for re-treatments and for auxiliary procedures as well as the incidence of complications was significantly higher in patients with stones of >1 cm. In patients with stones of ≤1 cm treated with ESWL the need for re-treatments and for auxiliary procedures as well as the incidence of complications was significantly lower than for those treated with URS.\n In centres where both techniques are available, ESWL should be the preferred treatment for patients with single distal ureteric stones of ≤1 cm and URS should be reserved for patients with stones of >1 cm.\n © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.", "To conduct a prospective and randomized trial to compare the efficiency quotient and cost-effectiveness index of shock wave lithotripsy (SWL) and ureteroscopic lithotripsy (URSL) for the treatment of large upper third ureteral stones.\n A total of 35 male patients and 7 female patients with a solitary, radiopaque upper ureteral stone, 15 mm or more in diameter, who underwent SWL or URSL were enrolled in this study. The mean patient age was 53.1 +/- 14.5 years. The endpoint of the study was for the patient to be stone free or to have insignificant residual stone (3 mm or less) within the kidney.\n The mean stone length +/- SD was 17.9 +/- 3.9 cm in the SWL group and 18.5 +/- 2.9 cm in the URSL group (P > 0.05). The efficiency quotient for SWL and URSL was 0.61 and 0.63, respectively. The cost-effectiveness index, treatment time, pain score, and hospital stay were greater in the URSL group. However, the degree of hydronephrosis significantly influenced the success rate of SWL. All patients with severe hydronephrosis in the SWL group needed auxiliary surgical procedures to become stone free.\n The efficiency quotients of SWL and URSL were comparable in the treatment of large upper third ureteral stones. However, SWL should not be recommended as the first-line treatment option for the management of upper third ureteral stones larger than 1.5 cm with severe hydronephrosis. Understanding the cost-effectiveness, success rate, pain score, and patient satisfaction score for the two different approaches constitutes the indispensable requisites for choosing the optimal first-line therapeutic strategy.", "In a randomized study, we analyzed the treatment results of ureterorenoscopy (URS) and shockwave lithotripsy (SWL) for extended-mid and distal ureteral stones. We investigated also, for reasons of cost effectiveness, the factors influencing the outcome, the complications, and the need for auxiliary procedures.\n In three regional hospitals, we selected 156 patients with extended-mid and distal ureteral stones. After randomization, 87 were treated with URS, and 69 with SWL. The treatment results were studied in relation to complications, the need for auxiliary procedures and stone factors, urinary tract infection (UTI), dilatation, and kidney function.\n After retreatment of 45% of the patients, the stone-free rate after 12 weeks in the SWL group was 51%. After a retreatment rate of 9% of the patients in the URS group, the stone-free rate was 91%. Including the number of auxiliary procedures, we calculated the Efficiency Quotient (EQ) as 0.50 for SWL and 0.38 for URS. After correction and redefinition of auxiliary procedures, the EQ was 0.66. The mean treatment time for SWL was 52 minutes and for URS 39 minutes. General anesthesia was more frequently needed in URS patients. Complications occurred more often in the URS group (22 v 3 and 24 v 13, respectively). These were mostly mild, and all could be treated with a double-J stent, antibiotics, or analgetics. A lower stone-free rate was achieved in patients with larger (> or =11 mm) stones (75% v 85% for smaller stones in the URS group and 17% v 73% in the SWL group. In the URS group, the stone-free rate of patients with extended-mid ureteral stones was lower than that of patients with distal ureteral stones. Calculating the costs for URS and SWL appeared impossible because of the differences in available equipment.\n The stone-free rate after URS is much higher than after SWL, and the EQ in our series was strongly dependent on definitions. The decision about how to treat a patient with an extended-mid or distal ureteral stone therefore should not be made primarily on the basis of cost effectiveness but rather on the basis of the availability of proper equipment, the experience of the urologist, and the preference of the patient.", "To compare the efficacy and complications of extracorporeal shock-wave lithotripsy (SWL) and pneumatic ureteroscopic lithotripsy (URS) in the treatment of lower ureteral calculi.\n From August 1997 to June 1999, 210 patients with calculi in the distal third of the ureter were treated with SWL and the other 180 with URS. The stones were fragmented with either HB-ESWL-V lithotripter or JML-93 pneumatic lithotripter through Wolf 7.5 approximately 9.0 Fr ureteroscope. The outcome was assessed in terms of stone clearance rate, re-treatment rate and complication incidence.\n The stone clearance rate was 78.1 % with SWL and 93.3 % with URS (P<0.05). SWL had a re-treatment rate of 11.9 %, vs 2.2 % in the URS group (P<0.05). URS caused ureteral perforation in 3.3% of patients, while it was 0 with SWL (P<0.05). The differences in the incidence of other complications such as infection and stricture between the two groups were insignificant.\n Though the selection of these two options depends on equipments available and the expertise of the operator, we recommend URS as the optimal treatment for distal ureteral calculi.", "To conduct a prospective randomized study comparing both techniques for the management of solitary radio-opaque upper ureteral stones < 2 cm in diameter. The ideal treatment for upper ureteral stones > 1 cm size remains to be determined with shock wave lithotripsy (SWL) and ureteroscopy (URS) being acceptable options.\n A total of 200 patients were included in the study. They were randomized into 2 equal groups. Group A underwent in situ SWL as a primary therapy. Group B underwent URS, using semirigid URS with intracorporeal lithotripsy. Efficiency quotient (EQ), cost analysis, and predictors of failure were estimated for both techniques.\n For stones of size > or = 1 cm, the initial stone-free rate for URS and SWL was 88% and 60%, respectively. The estimated EQ was 0.79 and 0.43 for both techniques respectively. For stones < 1 cm, the initial stone-free rate for URS and SWL was 100% and 80%, respectively. The estimated EQ was 0.88 and 0.70 for both techniques, respectively. The mean cumulative costs were significantly more in SWL group (P <.05). Predictors of URS failure included; male gender, failure to pass guidewire beyond the stone, and extravasation. Predictors of SWL failure included large stone size > 1 cm, calcium oxalate monohydrate stone, and higher degrees of hydronephrosis.\n URS with intracorporeal lithotripsy is an acceptable treatment modality for all proximal ureteral calculi, particularly stones > 1 cm. SWL should remain the first-line therapy for proximal ureteral calculi < or = 1 cm because of the less invasive nature and lower anesthesia (i.v. sedation)." ]

[ "15457381", "16481296", "12235507", "11961625" ]

[ "The AESOP robot system in laparoscopic surgery: increased risk or advantage for surgeon and patient?", "Zeus robot-assisted laparoscopic cholecystectomy in comparison with conventional laparoscopic cholecystectomy.", "Controlled trial of the introduction of a robotic camera assistant (EndoAssist) for laparoscopic cholecystectomy.", "Time-action analysis of instrument positioners in laparoscopic cholecystectomy." ]

[ "The aim of this study was to examine the advantages and risks of the Automated Endoscopic System for Optical Positioning (AESOP) 3000 robot system during uncomplicated laparoscopic cholecystectomies or laparoscopic hernioplasty.\n In a randomized study, we examined two groups of 120 patients each with the diagnosis cholecystolithiasis respectively the unilateral inguinal hernia. We worked with the AESOP 3000, a robotic arm system that is voice-controlled by the surgeon. The subjective and objective comfort of the surgeon as well as the course and length of the operation were measured.\n The robot-assisted operations required significantly longer preparation and operation times. With regard to the necessary commands and manual camera corrections, the assistant group was favored. The same was true for the subjective evaluation of the surgical course by the surgeon.\n Our study showed that the use of AESOP during laparoscopic cholecystectomy and hernioplasty is possible in 94% of all cases. The surgeon must accept a definite loss of comfort as well as a certain loss of time against the advantage of saving on personnel.", "The robotic surgical system overcomes many technological obstacles of conventional laparoscopic surgery, and possesses enormous clinical applied potential. The aim of this study was to compare the efficacy of Zeus robot-assisted laparoscopic cholecystectomy with conventional laparoscopic cholecystectomy.\n Forty patients undergoing elective cholecystectomy were randomly divided into two groups. Patients in group A (n=20) underwent Zeus robot-assisted laparoscopic cholecystectomy, and patients in group B (n=20) received conventional laparoscopic cholecystectomy. The parameters on operative field, operative time, the number of actions, the rate of operative errors and minimal trauma were evaluated and compared between the two groups.\n The number of clearing camera (1.1+/-1.0 times) and the time of adjusting the operative field (2.2+/-0.7 minutes) in group A were significantly less than those (4.5+/-1.5 times) and (7.5+/-1.2 minutes) in group B. The number of dissection actions (337+/-86 times) and the rate of operative errors (10%) in group A were less than those (389+/-94 times), (25%) in group B. The total operation time (104.9+/-20.5 minutes) and setup time (29.5+/-9.8 minutes) in group A were significantly longer than those (78.6+/-17.1 minutes), (12.6+/-2.5 minutes) in group B. Blood loss and postoperative hospitalization were similar. No postoperative complications occurred in both groups, and open cholecystectomy was performed in each group.\n Zeus robot-assisted cholecystectomy inherits the benefits of minimally invasive surgery. The Zeus robotic surgical system is better than conventional laparoscopic technique in controlling the operative field and can be manipulated precisely and stably though it requires more operative time.", "The role of the human camera holder during laparoscopic surgery keeps valuable personnel from other duties. EndoAssist is a robotic camera-holding device controlled by the operator's head movements. This study assesses its introduction into clinical practice.\n Ninety-three patients undergoing laparoscopic cholecystectomy were randomized to have either the robotic (40) or a human (46) assistant. Seven patients converted to open operation were excluded. Six surgeons were evaluated. Operating time and subjective assessments were recorded. Learning curves were constructed.\n The mean operating time was less using the robotic assistant (66 min) than with human assistance (74 min) (p < 0.05, two-tailed t-test). The learning curves for operating time showed that within three operations surgeons were trained in using the robot. The device was safe in use.\n The EndoAssist operating device is a significant asset in laparoscopic surgery and a suitable substitute for a human assistant. Surgeons became competent in the use of the robot within three operations. The robot offers stability and good control of the television image in laparoscopic surgery.", "Instrument positioners can position and lock a laparoscopic instrument. This study uses time-action analysis to evaluate objectively whether IPs can substitute for a surgical assistant efficiently and safely.\n In four hospitals, 78 laparoscopic cholecystectomies were randomly assisted by a surgical assistant or an instrument positioner (AESOP and PASSIST) The efficiency and safety of laparoscopic cholecystectomies were analyzed with respect to time, number and type of actions, positioning accuracy, and peroperative complications. A questionnaire evaluated the difficulties for each operation and the comfort of instrument positioner use.\n The PASSIST and AESOP were able to replace the surgical assistant during laparoscopic cholecystectomies without significantly changing either the efficiency or the safety of the operation. The questionnaire showed that the surgeons preferred to operate with an instrument positioner.\n This study assessed objectively that instrument positioners can substitute for a surgical assistant efficiently and safely in elective laparoscopic cholecystectomies." ]

[ "11242425", "16212203", "10197569", "7914260", "8474804", "8704753", "9347292", "20566605", "10496824", "8155936", "3566318", "15293973", "8422872", "6880729", "1559523", "6706688" ]

[ "Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus.", "Effect of exclusive breastfeeding and complementary feeding on infant growth and morbidity.", "Age of introduction of complementary foods and growth of term, low-birth-weight, breast-fed infants: a randomized intervention study in Honduras.", "Effects of age of introduction of complementary foods on infant breast milk intake, total energy intake, and growth: a randomised intervention study in Honduras.", "Exclusive breast-feeding for at least 4 months protects against otitis media.", "Breast-feeding and the nutritional status of nursing children in Chile.", "Age at introduction of complementary food and physical growth from 2 to 9 months in rural Senegal.", "Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy.", "Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study.", "Intake and growth of breast-fed and formula-fed infants in relation to the timing of introduction of complementary foods: the DARLING study. Davis Area Research on Lactation, Infant Nutrition and Growth.", "Prolonged exclusive breast feeding and heredity as determinants in infantile atopy.", "The first six month growth and illness of exclusively and non-exclusively breast-fed infants in Nigeria.", "Growth dynamics during the first two years of life: a prospective study in the Philippines.", "Prophylaxis of atopic disease by six months' total solid food elimination. Evaluation of 135 exclusively breast-fed infants of atopic families.", "Prolonged breast-feeding and malnutrition among rural Indian children below 3 years of age.", "Breastfeeding, growth and diarrhoea in rural Bangladesh children." ]

[ "Current evidence that breastfeeding is beneficial for infant and child health is based exclusively on observational studies. Potential sources of bias in such studies have led to doubts about the magnitude of these health benefits in industrialized countries.\n To assess the effects of breastfeeding promotion on breastfeeding duration and exclusivity and gastrointestinal and respiratory infection and atopic eczema among infants.\n The Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial conducted June 1996-December 1997 with a 1-year follow-up.\n Thirty-one maternity hospitals and polyclinics in the Republic of Belarus.\n A total of 17 046 mother-infant pairs consisting of full-term singleton infants weighing at least 2500 g and their healthy mothers who intended to breastfeed, 16491 (96.7%) of which completed the entire 12 months of follow-up.\n Sites were randomly assigned to receive an experimental intervention (n = 16) modeled on the Baby-Friendly Hospital Initiative of the World Health Organization and United Nations Children's Fund, which emphasizes health care worker assistance with initiating and maintaining breastfeeding and lactation and postnatal breastfeeding support, or a control intervention (n = 15) of continuing usual infant feeding practices and policies.\n Duration of any breastfeeding, prevalence of predominant and exclusive breastfeeding at 3 and 6 months of life and occurrence of 1 or more episodes of gastrointestinal tract infection, 2 or more episodes of respiratory tract infection, and atopic eczema during the first 12 months of life, compared between the intervention and control groups.\n Infants from the intervention sites were significantly more likely than control infants to be breastfed to any degree at 12 months (19.7% vs 11.4%; adjusted odds ratio [OR], 0.47; 95% confidence interval [CI], 0.32-0.69), were more likely to be exclusively breastfed at 3 months (43.3% vs 6.4%; P<.001) and at 6 months (7.9% vs 0.6%; P =.01), and had a significant reduction in the risk of 1 or more gastrointestinal tract infections (9.1% vs 13.2%; adjusted OR, 0.60; 95% CI, 0.40-0.91) and of atopic eczema (3.3% vs 6.3%; adjusted OR, 0.54; 95% CI, 0.31-0.95), but no significant reduction in respiratory tract infection (intervention group, 39.2%; control group, 39.4%; adjusted OR, 0.87; 95% CI, 0.59-1.28).\n Our experimental intervention increased the duration and degree (exclusivity) of breastfeeding and decreased the risk of gastrointestinal tract infection and atopic eczema in the first year of life. These results provide a solid scientific underpinning for future interventions to promote breastfeeding.", "A cohort study was conducted in the Islamic Republic of Iran between January 1997 and February 1998 to compare the growth and morbidity of 100 infants who were exclusively breastfed for 6 months and 100 who received breast milk and complementary foods between 4-6 months. Infants' feeding pattern, weight and height were assessed and recorded. There were no significant differences in infants' weight and height gain between 4 and 6 months. The rate of diarrhoea between ages 4 and 6 months was significantly lower in exclusively breastfed infants than in complementary food-fed infants (11% versus 27%) and respiratory infections were also lower (23% versus 35%). We conclude that exclusive breastfeeding is superior at least until an infant is 6 months of age.", "The optimal age at which to introduce complementary foods is a topic of considerable debate.\n This study was designed to evaluate this issue in a nutritionally vulnerable population in Honduras.\n Mothers of low-birth-weight (1500-2500 g) term (ie, small-for-gestational-age) infants were recruited in the hospital and assisted with exclusive breast-feeding during the first 4 mo. At 4 mo, mothers were randomly assigned to either continue exclusive breast-feeding to 6 mo (EBF; n = 59) or to feed complementary solid foods (jarred rice cereal, chicken, and fruit and vegetables) twice daily from 4 to 6 mo while continuing to breast-feed at their initial frequency (SF; n = 60). At 4 and 6 mo, breast milk and total energy intake were measured for a nonrandom subsample (those who could stay overnight in a central unit: 32 EBF and 31 SF).\n At 4 mo, breast milk intake in the subsample was not significantly different between groups (EBF: 729 +/- 135 g/d; SF: 683 +/- 151 g/d: P >0.2); from 4 to 6 mo it increased (by 28 g/d) in the EBF group but decreased (by 39 g/d) in the SF group (P < 0.005). Nonetheless, total energy intake (including solid foods) increased more from 4 to 6 mo in the SF than in the EBF group. However, there were no significant differences between groups in weight or length gain during the intervention or subsequently (6-12 mo).\n There was no growth advantage of complementary feeding of small-for-gestational-age, breast-fed infants between 4 and 6 mo of age.", "In developing countries, the age at which breastfed infants are first given complementary foods is of public health importance because of the risk of diarrhoeal disease from contaminated weaning foods, and the potential risk of growth faltering if foods are inappropriately delayed. To evaluate whether there are any advantage of complementary feeding prior to 6 months, low-income primiparous mothers who had exclusively breastfed for 4 months were randomly assigned to one of 3 groups: continued exclusive breastfeeding to 6 months (EBF) (n = 50); introduction of complementary foods at 4 months with ad libitum nursing from 4-6 months (SF) (n = 47); and introduction of complementary foods at 4 months, with maintenance of baseline nursing frequency from 4-6 months (SF-M) (n = 44). Baby foods in jars were provided to the SF and SF-M groups from 4 to 6 months. Subjects were visited weekly and provided with lactation guidance; at 4, 5, and 6 months measurements were made of infant intake and breast milk composition. At 4 months, breast milk intake averaged 797 (139) g per day (no difference among groups). Between 4 and 6 months, breast milk intake was unchanged in EBF infants (+6) but decreased in the SF (-103), and SF-M (-62) groups (p < 0.001). Change in total energy intake (including solid foods) and infant weight and length gain did not differ significantly between groups. Weight and length gain from 4-6 months were comparable to those of breastfed infants in an affluent USA population. The results indicate that breastfed infants self-regulate their total energy intake when other foods are introduced. As a result, there is no advantage in introducing complementary foods before 6 months in this population, whereas there may be disadvantages if there is increased exposure to contaminated weaning foods.", "This study was designed to assess the relation of exclusive breast-feeding, independent of recognized risk factors, to acute and recurrent otitis media in the first 12 months of life.\n Records of 1220 infants who used a health maintenance organization and who were followed during their first year of life as part of the Tucson Children's Respiratory Study were reviewed. Detailed prospective information about the duration and exclusiveness of breast-feeding was obtained, as was information relative to potential risk factors (socioeconomic status, gender, number of siblings, use of day care, maternal smoking, and family history of allergy). Acute otitis media and recurrent otitis media, defined as three or more episodes of acute otitis media in a 6-month period or four episodes in 12 months, were the outcome variables.\n Of the 1013 infants followed for their entire first year, 476 (47%) had at least one episode of otitis and 169 (17%) had recurrent otitis media. Infants exclusively breast-fed for 4 or more months had half the mean number of acute otitis media episodes as did those not breastfed at all and 40% less than those infants whose diets were supplemented with other foods prior to 4 months. The recurrent otitis media rate in infants exclusively breast-fed for 6 months or more was 10% and was 20.5% in those infants who breast-fed for less than 4 months. This protection was independent of the risk factors considered.\n These findings suggest that exclusive breast-feeding of 4 or more months protected infants from single and recurrent episodes of otitis media.", "The work reported here sought to describe the feeding patterns of Chilean children up to 18 months old and their relation to nutritional status. To this end, a survey was conducted in 1993 of 9330 Chilean children under 18 months old who were receiving care through the National Health Service System-which provides care for 75% of all children under age 6. The children, whose mothers or caretakers were interviewed, constituted 94% of a sample selected at random from 102 of the 320 urban health clinics located throughout the country. The interview served to identify the type of feeding (exclusive breast-feeding, breast-feeding plus bottle-feeding, breast-feeding plus solid food, exclusive bottle-feeding, or bottle-feeding plus solid food) and to determine the nutritional status of the participants in terms of standards used by the United States National Center for Health Statistics and the World Health Organization. Children were deemed at risk of malnutrition if they had z scores on the weight-for-age distribution between 1.0 and 2.0 standard deviations below the US/WHO standard and as actually malnourished if they had z scores of over 2.0 standard deviations below the standard. The survey found exclusive breast-feeding prevalences of 86.5%, 66.7%, and 25.3% among infants 1, 3, and 6 months old. Some 12.1% of the participants were found to have a weight-for-age deficiency, 30.7% exhibited a height-for-age deficiency, and 35.7% were found to be over-weight. The prevalence of weight-for-age and height-for-age deficiencies were found to be considerably higher among bottle-fed children than among breast-fed children. In general, the results demonstrated the benefits of exclusive breast-feeding through the first 6 months of life, the need to complement exclusive breast-feeding with solid food after that time, and the superior nutritional status of breast-fed children within the age groups studied.", "To compare nutritional status and physical growth among infants according to age at introduction of complementary food (CF).\n A longitudinal observational study.\n Three health clinics in a rural area of Senegal.\n During immunization sessions, 522 infants were recruited at 2-3 months. Complete data on three visits were available for 420 infants (4 visits: n = 361); 73 were lost to follow-up and 29 had incomplete data.\n Increments in length and weight between adjacent visits.\n Infants complemented at 2-3 months (n = 50) had significantly lower length-for-age (P = 0.014), weight-for-length (P < 0.001) and arm circumference (P < 0.0001) at 2-3 months than predominantly breastfed infants (n = 370), after adjustment for residence, mother's age and education of parents. The growth in weight and length from 2-3 to 9-10 months did not differ. The infants complemented by 4-5 months, but not yet at 2-3 months, (n = 94) had a slightly lower length increment from 4-5 to 6-7 months (1.42 vs 1.53 cm/mo, p < 0.05) compared to infants predominantly breastfed at 4-5 months (n = 276). The infants first complemented by 6-7 months (n = 122) had increments from 6-7 to 9-10 months similar to those of predominantly breastfed infants (n = 154).\n Introduction of CF by 2-3 months was associated with a low nutritional status, but not with slow growth from 2-3 to 9-10 months. Introduction of CF by 4-5 months was associated with slightly slower linear growth compared to later introduction.", "To examine the associations of duration of exclusive breastfeeding with infections in the upper respiratory (URTI), lower respiratory (LRTI), and gastrointestinal tracts (GI) in infancy.\n This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life onward in the Netherlands. Rates of breastfeeding during the first 6 months (never; partial for <4 months, not thereafter; partial for 4-6 months; exclusive for 4 months, not thereafter; exclusive for 4 months, partial thereafter; and exclusive for 6 months) and doctor-attended infections in the URTI, LRTI, and GI until the age of 12 months were assessed by questionnaires and available for 4164 subjects.\n Compared with never-breastfed infants, those who were breastfed exclusively until the age of 4 months and partially thereafter had lower risks of infections in the URTI, LRTI, and GI until the age of 6 months (adjusted odds ratio [aOR]: 0.65 [95% confidence interval (CI): 0.51-0.83]; aOR: 0.50 [CI: 0.32-0.79]; and aOR: 0.41 [CI: 0.26-0.64], respectively) and of LRTI infections between the ages of 7 and 12 months (aOR: 0.46 [CI: 0.31-0.69]). Similar tendencies were observed for infants who were exclusively breastfed for 6 months or longer. Partial breastfeeding, even for 6 months, did not result in significantly lower risks of these infections.\n Exclusive breastfeeding until the age of 4 months and partially thereafter was associated with a significant reduction of respiratory and gastrointestinal morbidity in infants. Our findings support health-policy strategies to promote exclusive breastfeeding for at least 4 months, but preferably 6 months, in industrialized countries.", "To investigate the association between the duration of exclusive breast feeding and the development of asthma related outcomes in children at age 6 years.\n Prospective cohort study.\n Western Australia.\n 2187 children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth and followed to age 6 years.\n Unconditional logistic regression to model the association between duration of exclusive breast feeding and outcomes related to asthma or atopy at 6 years of age, allowing for several important confounders: sex, gestational age, smoking in the household, and early childcare.\n After adjustment for confounders, the introduction of milk other than breast milk before 4 months of age was a significant risk factor for all asthma and atopy related outcomes in children aged 6 years: asthma diagnosed by a doctor (odds ratio 1.25, 95% confidence interval 1.02 to 1.52); wheeze three or more times since 1 year of age (1.41, 1.14 to 1.76); wheeze in the past year (1.31, 1.05 to 1.64); sleep disturbance due to wheeze within the past year (1.42, 1.07 to 1.89); age when doctor diagnosed asthma (hazard ratio 1.22, 1.03 to 1.43); age at first wheeze (1.36, 1.17 to 1.59); and positive skin prick test reaction to at least one common aeroallergen (1.30, 1.04 to 1.61).\n A significant reduction in the risk of childhood asthma at age 6 years occurs if exclusive breast feeding is continued for at least the 4 months after birth. These findings are important for our understanding of the cause of childhood asthma and suggest that public health interventions to optimise breast feeding may help to reduce the community burden of childhood asthma and its associated traits.", "We examined if the timing of introduction of solid foods was related to growth, intake, morbidity, activity or motor development among infants either breast fed or formula fed until > or = 12 months of age. Breast-fed infants given solids before 6 months of age (earlysol) consumed less breast milk at 6 and 9 months of age than those given solids > or = 6 months (latesol); thus total energy intake did not differ between groups. Z scores for weight, length and weight-for-length at 1-18 months did not differ between groups. Latesol infants gained less weight from 6 to 9 months but not during any other interval. Neither activity level nor morbidity differed between groups, but several developmental milestones occurred earlier in the earlysol versus the latesol group, probably due to reverse causation. Among formula-fed infants, timing of introduction of solid foods was not related to intake, growth, activity or morbidity. We conclude that solid foods given before 6 months of age generally replace the milk source among breast-fed but not formula-fed infants.", "We followed 183 infants for two years, 31 of whom were breast fed less than three and a half months (median 70 days; short breast feeding group) and a further 31 of whom were exclusively breast fed for more than nine months (long breast feeding group). We assessed heredity for atopy, number of infections, and duration of breast feeding as determinants of atopy. During the first year of life 14 infants has signs of atopy. During the second year parents reported signs of atopy in a further 31. Heredity was the only significant predictor of atopy. Atopy was seen in 33% of infants with a positive heredity and in 16% without family history for atopy. The duration of breast feeding affected the incidence of atopy only among the infants without family history for atopy: fewer in the short breast feeding group (1/18) had atopy than in the long breast feeding group (5/13). Duration of breast feeding did not associate with incidence of respiratory infections. Diarrhoea was more common in the short breast feeding group than in the long breast feeding group during the first year of life. We conclude that prolonging exclusive breast feeding from the median of 70 days to nine months did not contribute to the prevention of infantile atopy and respiratory tract infections.", "To compare the growth and illness pattern of infants who were exclusively breast fed for six months with those of infants commenced on complementary feeding before the age of six months and ascertain reasons for the early introduction of complementary feeding.\n A comparative prospective study.\n Urban Comprehensive Health Centre (UCHC), Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife.\n Three hundred and fifty-two mothers and their normal birth weight babies, weighing 2.500kg or more, and aged less than 14 days were serially recruited into the study.\n Mean/median monthly weights in the first six months of life, history/outpatient presentation for illnesses.\n Of the 352 mother-infant pairs recruited into the study, 345 (98%) were successfully followed up for the first six months of life. At six months, 264 (76.5%) were exclusively breast-fed, 45 (13.1%) were started on complementary feeding, between the ages of four and six months while 36 (10.4%) commenced complementary feeding before the age of four months. Infants who were exclusively breast-fed for six months had median weights above the 50th percentiles of the WHO/NCHS reference that is currently used in the national \"road to health\" (growth monitoring) cards. Furthermore, the mean weight of these babies at age six months was above those of babies who started complementary foods before six months. They also reported fewer symptoms and had fewer illness episodes (0.1 episodes per child) compared to those who started complementary feeding before six months. Infants who commenced complementary feeding before four months reported more symptoms and had more illness episodes (1.4 episodes per child) compared to those that commenced complementary feeding between four and six months (1.2 episodes per child). Common symptoms/illnesses seen or reported during the study among the groups were fever, diarrhoea and cough. Reasons given for early introduction of complementary foods include insufficient breast milk, thirst and convenience.\n It is concluded that exclusive breast-feeding supported adequate growth during the first six months of life for most of the infants studied. Early introduction of complementary foods did not provide any advantages in terms of weight gain in our environment, it was frequently associated with illness episodes and growth faltering. Many mothers however require support, encouragement and access to health care providers to breastfeed exclusively for the first six months of life.", "This study examines determinants of growth from birth to 24 months in a sample of approximately 3000 urban and rural Filipino children. Individual, household, and community data were collected bimonthly during the Cebu Longitudinal Health and Nutrition Survey. Separate longitudinal, multivariate models were used to identify determinants of weight in children from birth to 6 months and 6-24 months of age. Previous weight, male gender, mother's height, and season of the year showed significant positive associations with weight in all models. Full and mixed breast-feeding significantly increased weight, but the effects of breast-feeding declined as children got older. Breast-feeding had a direct growth-enhancing effect in addition to its indirect effect through the prevention of diarrheal morbidity. Detrimental effects of recent diarrheal morbidity were particularly important in the older age group, but these effects were mitigated by breast-feeding. Since infant feeding variables are included in the models, the results strongly suggest an effect of diarrheal morbidity on growth independent of its known effects on infant feeding and dietary intake. Febrile respiratory infections had important detrimental effects on weight in both age groups.", "One hundred and thirty-five infants of atopic parents were exclusively breast-fed for 6 months without any cow's milk based supplements. Of these infants 70 received no nourishment except breast milk during the 6 months, and 65 were started on solid foods at the age of 3 months. The diet of all the infants was similar during 6 to 12 months of age. The children were examined at the age of one year. In the exclusive breast milk group atopic eczema and food allergy were less frequent than in the solid food group. The results suggest that total solid food elimination for the first 6 months of life, in addition to exclusive breast milk feeding, is prophylactic for atopic disease in children who are at hereditary risk.", "Long periods of exclusive as well as partial breast-feeding in poor communities are of considerable importance from a nutritional standpoint, as it is in these communities that malnutrition is predominant. Although benefits of exclusive breast feeding have been well documented, those for partial breast-feeding have not been examined. The present study in particular examines the effects of prolonged breast-feeding, i.e. exclusive breast-feeding beyond 6 months or partial breast-feeding up to 2-3 years, in terms of prevalent malnutrition and morbidity among rural children. A total of 395 children were observed for weight, height, information on duration of breast-feeding, age at weaning and morbidity in terms of recent illness in the 7 days prior to the day of visit. Exclusive breast-feeding beyond 6 months and up to 12 months appeared beneficial in terms of reduced morbidity. Beyond infancy, there was no evidence of any protective effect of partial breast-feeding. This could be due to poor lactational performance of mothers and their unawareness about it resulting in inadequate weaning foods being offered to partially breast-fed children. Significant differences in male and female children in the extent of malnutrition pointed towards discrimination against girls even in respect of exclusive breast-feeding. The study highlights the need for advocating proper weaning practices while recommending prolonged breast-feeding in poor communities.", "It has been observed that breastfeeding protects infants from many illnesses. We examined whether breastfeeding alone or with a supplement maintained normal growth and whether the incidence of diarrhoea was different in the two groups. The study was conducted on 223 children in a rural area. Anthropometric measurements were obtained every month up to 12 months and then every 3 months. The history of feeding was recorded. The mothers were visited weekly to record information on diarrhoeal illness. Homemade supplements were used. The average weight of exclusively breastfed children was not significantly different from that of those who were breastfed with supplements. The average weight paralleled the Harvard standard up to the 4th month, and the increase in height showed the same pattern. During the first year the incidences and duration of diarrhoeal attacks were higher in the exclusively breastfed children than in the supplemented groups. On average there were 3.2 attacks of diarrhoea per child per year and the average duration was 15.9 days per child per year during the first 2 years." ]

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[ "A comparison of patient-controlled analgesia and bolus PRN intravenous morphine in the intensive care environment.", "Efficacy and costs of patient-controlled analgesia versus regularly administered intramuscular opioid therapy.", "Patient controlled analgesia and intramuscular injections: a comparisons of patient pain experiences and postoperative outcomes.", "[Postoperative intravenous analgesia].", "Comparison between patient-controlled analgesia and intramuscular meperidine after thoracotomy.", "Patient-controlled analgesia vs. conventional intramuscular analgesia following colon surgery.", "A study of pain management: patient controlled analgesia versus intramuscular analgesia.", "Patient-controlled analgesia in children and adolescents: a randomized, prospective comparison with intramuscular administration of morphine for postoperative analgesia.", "Patient-controlled analgesia: a new concept of postoperative pain relief.", "Patient-controlled analgesia for post-cesarean section pain.", "Patient-controlled versus nurse-controlled pain treatment after coronary artery bypass surgery.", "Efficacy of patient-controlled versus conventional analgesia for postoperative pain.", "Patient-controlled analgesia: a controlled trial.", "Epidural narcotic and patient-controlled analgesia for post-cesarean section pain relief.", "A comparison of patient-controlled and fixed schedule analgesia after orthognathic surgery.", "Patient-controlled versus conventional analgesia for postsurgical pain relief in adolescents.", "Patient-controlled analgesia versus conventional intramuscular injection: a cost effectiveness analysis.", "Pain relief after abdominal surgery--a comparison of i.m. morphine, sublingual buprenorphine and self-administered i.v. pethidine.", "Patient-Controlled Analgesia Following Vertical Gastroplasty: a Comparison with Intramuscular Narcotics.", "Patient-controlled analgesia compared with intramuscular injection of analgesics for the management of pain after an orthopaedic procedure.", "Analgesia following major gynecological laparoscopic surgery--PCA versus intermittent intramuscular injection.", "Patient-controlled analgesia: a randomized, prospective comparison between two commercially available PCA pumps and conventional analgesic therapy for postoperative pain.", "A prospective randomized clinical trial on pain control after major abdominal surgery.", "Hypoxaemia and pain relief after upper abdominal surgery: comparison of i.m. and patient-controlled analgesia.", "A statistical model for pain in patient-controlled analgesia and conventional intramuscular opioid regimens.", "Patient-controlled analgesia versus intramuscular analgesic therapy.", "Pain following craniotomy: a preliminary study comparing PCA morphine with intramuscular codeine phosphate.", "Patient-controlled analgesia in gynecologic oncology surgery.", "Nurse-administered subcutaneous morphine is a satisfactory alternative to intravenous patient-controlled analgesia morphine after cardiac surgery.", "Patient-controlled analgesia following cesarean section: a comparison with epidural and intramuscular narcotics.", "A prospective study of patient-controlled analgesia. Impact on overall hospital course.", "Effects of patient-controlled analgesia on postoperative anxiety in elderly men.", "A comparison of morphine administered by patient-controlled analgesia and regularly scheduled intramuscular injection in severe, postoperative pain.", "[Efficiency of patient-controlled analgesia versus conventional analgesia in patients after thoracotomy].", "Comparison of patient-controlled analgesia and nurse-controlled infusion analgesia after cardiac surgery.", "Pain management in cardiac surgery patients: comparison between standard therapy and patient-controlled analgesia regimen.", "Reduction of postoperative morbidity following patient-controlled morphine.", "Psychological characteristics and the effectiveness of patient-controlled analgesia.", "[Usefulness of intravenous patient-controlled analgesia in the treatment of postoperative pain].", "Impact of patient-controlled analgesia on required nursing time and duration of postoperative recovery.", "Cost-effectiveness analysis of patient-controlled analgesia, intramuscular q.i.d. injection and p.r.n. injection for postoperative pain relief.", "A randomized comparison of patient-controlled versus standard analgesic requirements in patients undergoing cholecystectomy.", "Patient-controlled analgesia: a comparison with nurse-controlled intravenous opioid infusions.", "Pain control after cesarean birth. Efficacy of patient-controlled analgesia vs traditional therapy (IM morphine).", "Comparison between patient-controlled analgesia and subcutaneous morphine in elderly patients after total hip replacement.", "Patient-controlled analgesia compared with nurse-controlled infusion analgesia after heart surgery." ]

[ "We compared the use of patient-controlled analgesia (PCA) morphine and p.r.n. intravenous morphine in an intensive care unit setting. Thirty-eight patients scheduled for admission to the Surgical Intensive Care Unit (SICU) were prospectively randomized to either a PCA group or a p.r.n. intravenous morphine group. Assessments included pain and sedation scores, respiratory rates, pulse oximetry, and morphine utilization. PCA was found to be comparable in safety and efficacy to nurse-administered morphine in the intensive care environment. An unexpected finding was the higher initial morphine utilization seen in the patients utilizing PCA.", "Many studies have shown the efficacy of patient-controlled analgesia (PCA). However, it is not clear whether PCA has clinical or economic benefits in addition to efficient analgesia. The current study was designed to evaluate these issues by comparing PCA with regularly administered intramuscular injections of opioids after hysterectomy.\n This prospective study included 126 patients who underwent abdominal hysterectomy and were randomly assigned to receive PCA or regularly timed intramuscular injections of morphine during a period of 48 h. Doses were adjusted to provide satisfactory analgesia in both treatment groups. Pain at rest and with movement, functional recovery, drug side effects, and patient satisfaction were measured using rating scales and questionnaires. The costs of PCA and intramuscular therapy were calculated based on personnel time and drug and material requirements.\n Comparable analgesia was observed with the two treatment methods, with no significant differences in the incidence of side effects or patient satisfaction. The medication dosage had to be adjusted significantly more frequently in the intramuscular group than in the PCA patients. The PCA did not favor a faster recuperation time compared with intramuscular therapy in terms of times to ambulation, resumption of liquid and solid diet, passage of bowel gas, or hospital discharge. The results of the economic evaluation, which used a cost-minimization model and sensitivity analyses, showed that PCA was more costly than regular intramuscular injections despite the fact that no costs for the pump were included in the analyses. Cost differences in nursing time favoring PCA were offset by drug and material costs associated with this type of treatment.\n Compared with regularly scheduled intramuscular dosing, PCA is more costly and does not have clinical advantages for pain management after hysterectomy. Because of the comparable outcomes, the general use of PCA in similar patients should be questioned.", "Despite relatively widespread use of various forms of patient controlled analgesia (PCA), there remain conflicting results in the literature as to the efficacy of PCA. This study was conducted to assess the efficacy and postoperative outcomes of intravenous PCA compared to intramuscular (IM) injections in 73 patients who received major abdominal surgery. These patients were randomly selected and randomly assigned preoperatively to receiving IM or PCA modes of analgesia postoperatively. The following factors were compared: amount of pain; amount of analgesia use; degree of patient satisfaction with pain control both while on parenteral analgesia and after switching to oral; length of time to first ambulation; and length of stay in hospital. Results of the study did not demonstrate a statistically significant difference in any of these, using a P-value of 0.01. The PCA patients took an average of 4.5 hours longer than the IM patients to ambulate postoperatively and the IM patients received at least three times as much antiemetic (P = 0.001). Locus of control was not found to be a major factor in satisfaction or pain levels. Subsequent meta-analyses have also failed to yield significant differences between IM and PCA groups except in patient satisfaction. It is recommended that expansion of PCA programmes with abdominal surgery patients be considered only in cases where there is fiscal advantage or where patient satisfaction can be a driving force.", "The authors report the results of two clinical studies on postoperative pain relief with PCA. In the first clinical study 44 patients, undergoing gynecologic surgery, were assigned at random to two groups. The first was treated by PCA (infusor Baxter) with morphine i.v. (basal bolus 0.05 mg/kg, loading doses 1 mg every 6-15'), the second with 10 mg morphine i.m. at the end of surgery and then on demand with a lock-out of 6h at least. In the 2nd clinical study, 40 elder patients submitted to orthopedic surgery, were assigned at random to two groups treated with PCA (morphine i.v., basal bolus 0.07 mg/kg, bolus PCA 0.007 mg/kg lock-out 15') and with continuous infusion (i.c.) (basal bolus 0.07 mg/kg, i.c. 0.02 mg/kg/h). Our data were analyzed with Student's \"t\" unpaired test and showed lower doses of the drug in the groups PCA (1st study PCA 25.98 mg/48h, i.m. 45.45 mg/48h, 2nd study PCA 0.155 mg/kg/12h, i.c. 0.311 mg/kg/12h) and lower rate of side effects in the same groups. Side effects were well controlled using symptomatic drugs. We proposed to our patients, at the end of observation, a questionnaire about general conditions, sleep, pain evaluation using a descriptive scale and retrospective evaluation. Patients and nurses agree PCA. Nursing staff expressed a positive opinion and patients said they benefitted from PCA. As reported, PCA appears from our results, valid and safe in postoperative pain relief.", "A prospective randomized controlled study was performed to assess the efficacy and safety of patient-controlled analgesia (PCA) in patients undergoing thoracotomy. This method was compared with a conventional pain management technique consisting of regularly scheduled im injections of analgesics. Forty adult patients were randomly assigned to receive intravenous PCA or im meperidine treatment over a 48-hr period after surgery. Care was taken to optimize analgesia in patients of both groups. The McGill Pain Questionnaire, visual analogue and verbal-numeric scales were administered at regular intervals to measure various components of the patients' pain experience, degree of pain relief, adverse side effects and overall treatment efficacy. Functional recovery after surgery was also examined. The results showed good and comparable analgesia with both pain-control methods. However, a greater number of patients receiving im injections required dosage adjustments than in the PCA group. Patients' and nurses' evaluations of overall treatment efficacy also favoured PCA treatment. There were no major group differences in the side effect profile. Recovery pattern was also comparable in the two groups except for the length of hospitalisation. There were fewer long-stay patients in the PCA than in the im group. Meperidine intake was similar in both groups but considerable interpatient variation was seen. In conclusion, PCA is a safe, effective and individualized treatment method for controlling pain after thoracotomy. There appears to be some clinical advantages of PCA over im dosing regimens for analgesia after thoracotomy.", "Though patient-controlled analgesia (PCA) has been in use for over a decade, it has been popularized only recently. Conventional techniques of intermittent intramuscular (IM) administration of analgesia have fallen short of meeting the needs of patients following major abdominal surgery. This has prompted a search for methods to improve postoperative pain management. Though PCA has been accepted in many hospitals, few studies comparing conventional IM administration of morphine with PCA have been performed. A prospective randomized study comparing IM- and PCA-administered morphine in 62 patients undergoing colon surgery was performed. A comparison of the efficacy of analgesia and extent of sedation using these approaches shows that PCA allows for analgesia with less sedation and less drug requirement than that of IM administration. No differences were noted in postoperative duration of ileus, duration of hospitalization, and total hospital costs. This study confirms the safety and efficacy of PCA, and should be considered the current optimal method of controlling pain following major colonic surgery.", "A clinical study examining the efficacy of Patient Controlled Analgesia compared with Intramuscular Analgesia was conducted. Patient Controlled Analgesia (PCA) Therapy was used in a select group of patients after major abdominal surgery. Specific parameters monitored were: total amount of analgesia required, incidence of pulmonary complications, assessment of pain level and sedation, patient activity, nursing time required for administration, safety, cost-effectiveness of both modes of analgesia and length of hospital stay. A questionnaire survey of both patients and nursing staff was done to evaluate responses. Conventional pain management often is inadequate with PRN administration of analgesic drugs due to the unpredictable and uneven patient absorption rate and the individual pain intensity and tolerance. The patient experiences a repetitive cycle of pain and sedation. The patient on PCA therapy is able to titrate his analgesic medication very effectively and maintain a state of analgesia without sedation. He is more responsive and able to participate in the early postoperative rehabilitation phase. The transition to oral medication usually was accomplished at 48 hours postoperative.", "A randomized, prospective trial of patient-controlled analgesia (PCA), that is, a method of analgesia administration involving a computer-driven pump activated by patients to receive small doses within defined limits was performed in 82 children and adolescents after major orthopedic surgery to compare (1) intramuscularly administered morphine, (2) PCA morphine and (3) PCA morphine with a low-dose continuous morphine infusion (PCA-plus). Patients receiving PCA and PCA-plus had lower pain scores and greater satisfaction than patients receiving intramuscularly administered morphine. The three groups used equal amounts of morphine and most measures of recovery were identical in the groups. In particular, PCA and PCA-plus did not increase the incidence of opioid-related complications, and patients receiving PCA-plus were less sedated than patients receiving intramuscular therapy. We conclude that PCA and PCA-plus are safe and effective methods of pain relief in children and adolescents after orthopedic surgery, are better accepted than intramuscular injections, and do not increase perioperative morbidity.", "This report concerns evaluation of patient-controlled analgesia (PCA) in the form of two preliminary investigations. In the first study, the patient-controlled analgesia device, which consists of a pump linked to a timer so that patients can activate intravenous administration of morphine sulfate to themselves during the postoperative period, was used in seven morbidly obese patients. The amount of morphine used during the first 36 hours was found to vary between 32 and 185 mg, with a significant difference in drug usage when related to weight as well as to body surface area. In the second study, morbidly obese patients undergoing gastric bypass operations were prospectively randomized into 12 patients who used the PCA device in the postoperative period and 12 patients who were given standard intramuscular dosages of morphine sulfate. An analgesia and sedation scale was then used to compare the two groups. The patients in the PCA group were able to maintain a state of adequate analgesia without sleep with a significantly greater frequency than were those in the intramuscular injection group. On the basis of answers to a questionnaire given to the patient after 60 hours of morphine analgesia, it was apparent that the PCA group was much more satisfied with that form of postoperative analgesia. It would appear that PCA is an efficacious and safe method of providing for postoperative pain relief.", "Recent reports have suggested that patient-controlled analgesia is an effective means of narcotic administration in postoperative patients. This prospective investigation was undertaken to determine the efficacy and safety of patient-controlled anesthesia infusion after cesarean section. During a recent ten-month period, 130 patients were assigned randomly to receive meperidine by pump or intramuscular injection. Meperidine consumption using the device varied widely to meet individual needs. Overdosage and drug dependence were not encountered with the prescribed drug concentrations. The patient-controlled analgesia method provided less sedation and more immediate pain relief without the need for painful injections. The additional cost of renting the infuser device was offset by combined patient and nursing satisfaction. We conclude that patient-controlled infusion of meperidine is safe and effective in satisfying individual patient needs after cesarean section.", "Pain after coronary artery bypass surgery persists for several days. A continuous intravenous infusion of an opioid adequately accomplishes good pain control in the intensive care unit, but it is often not suitable on the ordinary ward. Patient-controlled analgesia (PCA) with intermittent injections delivered by one of the new devices now available could be an alternative to conventional nurse-controlled analgesia (NCA) based on intermittent injections. The aim was to compare these two techniques with respect to efficacy and the amount of opioid used.\n Forty-eight patients randomly received PCA or NCA with ketobemidone following extubation after coronary artery bypass grafting. Drug consumption, pain assessment with the visual analogue score (VAS) and possible side effects were evaluated from extubation to the end of the second postoperative day.\n On the day of surgery the VAS scores did not differ between the groups. From the afternoon of the first postoperative day the VAS scores were higher in the NCA group with mean values at 3-4 out of 10 as compared with mean values around 2 in the PCA group (P<0.01). During the study period the patients in the PCA group received more ketobemidone as compared with the NCA group, 61.9+/-24.0 mg and 36.3+/-20.2 mg, respectively (P<0.01). Additional oral analgesics were used in 12 of the patients in the NCA group compared with none in the PCA group. The few side effects reported were equally distributed between the two groups.\n PCA treatment after coronary artery bypass surgery resulted in better pain treatment and the use of more opioid without an increase in side effects compared with traditional NCA treatment.", "Patient-controlled i.v. administration and intramuscular administration of morphine sulfate were compared in a crossover study to determine their relative effectiveness in relieving postoperative pain. Twenty adult patients scheduled for abdominal surgery were randomly assigned to one of two groups; one group received i.v. morphine sulfate for 24 hours using a patient-controlled analgesia (PCA) device, after which they were given morphine sulfate i.m. for 24 hours. The treatment order was reversed for the other group. Amount of narcotic administered, respiratory rate, and levels of discomfort, activity, and sedation were assessed by the nursing staff every two hours. At the end of each 24-hour treatment phase, patients ranked their level of pain, amount of pain relief, level of sedation, ability to sleep, and ability to perform pulmonary toilet. Patients were also asked whether they preferred PCA or i.m. analgesic therapy for future surgery. Patients reported significantly less discomfort while using PCA than during i.m. morphine administration. No significant differences in amount of narcotic used, respiratory rate, nausea and vomiting, or levels of activity or sedation were noted for the two regimens. Patients' rankings of the two treatment modes did not differ significantly, but a majority of patients indicated a preference for future use of PCA. In these postoperative patients, administration of i.v. morphine sulfate by PCA was as safe as i.m. administration and possibly more effective in relieving pain.", "Thirty-six patients undergoing lower abdominal surgery were included in a prospective randomized controlled study to compare the effects of patient-controlled analgesia (PCA) and a standard intramuscular/intravenous treatment (conventional analgesia, CA) of postoperative pain. Morphine was used in both groups. There were no significant differences between the two analgesic regimens in respect of linear analogue pain scores, verbal pain-relief scores, amount of morphine used or side-effects. No treatment-induced alterations in vital values were experienced.", "nan", "The purpose of this prospective study was to compare the effectiveness of patient-controlled intravenous (i.v.) opioid analgesic administration (PCA) with fixed schedule and dosage oral/rectal administration of naproxen, and opioid analgesics intramuscularly/orally as needed (i.m./p.o. prn) for postoperative analgesia over a period of 48 to 56 hours after surgery.\n There were 75 orthognathic patients aged 25.73 +/- 8.01 years, subdivided into three study groups of 25: codeine group (8 males, 17 females); naproxen group (5 males, 20 females) and PCA group (8 male, 17 females). The degree of analgesia was assessed every 4 hours from 8:00 AM to 8:00 PM hours on days 1 and 2 postsurgery using a visual analog scale (VAS). Mean daily and mean overall VAS scores were treated as parametric data and were analyzed accordingly. Mean daily VAS scores also were categorized as comfort days when mean scores were less than 3.0 cm, and as discomfort days when mean scores were equal to or greater than 3.0 cm. ANOVA were used to analyze patient demographics, pain scores, surgical time, fentanyl used during general anaesthesia, analgesic morphine equivalents, and vital signs. Chi-square tests were used to analyze sex, comfort (discomfort) days, and nausea and vomiting. Mean VAS ratings were analyzed using independent t-tests.\n The three groups were matched in demographics, surgical time, fentanyl used, and sex. The PCA group used less than half the amount of morphine equivalent as the codeine group (P = .0001). Both the naproxen and the PCA groups were significantly more comfortable than the codeine group during day 1 and day 2 postsurgery. The codeine group had significantly more episodes of nausea than either the naproxen or the PCA groups.\n In patients undergoing orthognathic surgery, the naproxen and PCA regimens provided better analgesia than the codeine regimen.", "We performed a randomized nonblinded, cross-over comparison of patient-controlled analgesia (PCA) with conventional intramuscular analgesia in 10 adolescents (13-18 years) undergoing spinal fusion for idiopathic scoliosis. PCA use afforded more effective pain control (p < 0.02) on a 10-point linear pain intensity scale than did intramuscular injections, while causing an equal amount of sedation and no side effects. PCA appears to be a promising technique for providing postoperative pain relief in this group of adolescents. Further studies are needed to define its role for other pediatric conditions.", "In previous studies comparing patient-controlled-analgesia and intramuscular pain management have been unable to provide conclusive evidence of the benefits of either method of postoperative pain control.\n The purpose of the study was to compare the efficacy and cost-effectiveness of intravenous patient-controlled-analgesia with intermittent intramuscular morphine for Chinese women in the first 24 hours following elective gynaecological surgery.\n A randomized control design was used. The main outcomes were level of pain and cost for the two types of pain management. Participants indicated their level of pain at rest and when deep breathing or coughing on a 100 mm Visual Analogue Scale, on seven occasions within 24 postoperative hours. Costs for the two types of pain management were based on the costs of equipment, drugs and nursing time.\n A total of 125 women participated in the study. Mean pain level over the 24 hours in the patient-controlled-analgesia group was significantly lower than in the intramuscular group (P < 0.001). Mean pain level over the seven occasions for the patient-controlled-analgesia group was 11.83 points (95% CI 7.14-16.52) lower when at rest and 11.73 points (95% CI 5.96-17.50) lower during motion than the intramuscular group. Cost per patient was $81.10 (Hong Kong) higher for patient-controlled-analgesia than for intramuscular pain management. Women in the patient-controlled-analgesia group had significantly greater satisfaction with pain management than those in the intramuscular group (P < 0.001), but reported significantly more episodes of nausea (P < 0.05).\n While patient-controlled-analgesia was more costly, it was also more effective than conventional on-demand intramuscular opioid injections after laparotomy for gynaecological surgery.", "One hundred and twenty-six patients undergoing upper and lower abdominal surgery were studied after operation to compare the analgesic effects of i.m. morphine, sublingual buprenorphine and self-administered i.v. pethidine by Cardiff Palliator. There were no significant differences between analgesic regimens in respect of subjective linear analogue pain scores or static and dynamic lung volumes assessed at 24 and 48 h after operation and 5 days after operation in patients who underwent upper abdominal surgery. Sublingual buprenorphine produced more nausea and sedation than the other two treatments, but the differences were not clinically important. However, it offered considerable advantages in terms of ease of administration.", "BACKGROUND: patient-controlled analgesia PCA is a rapidly spreading approach to the management of post-operative pain. The suitability of this method for the morbidly obese patient undergoing bariatric surgery has not yet been determined. METHODS: in the present study we randomly compared two groups of patients undergoing silastic ring vertical gastroplasty. One group received PCA (12 patients) and the other (11 patients) received intermittent doses of pethidine intramuscularly. RESULTS: the cumulative morphine use during the first post-operative day was 52.71 +/- 1.83 mg by the PCA group and an equivalent of 24.55 +/- 3.42 mg morphine by the IM pethidine group (p = 0.0002). The analgesic and sedative effects by the PCA were found to be superior. There were no significant differences between the groups in the incidence of side-effects or complications, except a higher, unexplained incidence of wound infection in the PCA group. CONCLUSION: use of PCA in patients undergoing bariatric surgery has obvious advantages and appears to be a safe procedure.", "Patients who were scheduled for an elective joint replacement or spinal procedure were randomly assigned prospectively to one of two groups for the management of postoperative pain: ninety-one patients (Group I) controlled the administration of a narcotic analgesic themselves and ninety-three patients (Group II) received intramuscular injections of a narcotic analgesic, as needed. The patients who controlled the analgesic used a smaller amount of the analgesic on the first postoperative day, but the over-all amount was not significantly different between the two groups. The group that received intramuscular injections reported less pain overall, according to one of three pain-assessment scales, and had more relief of pain over-all and on the first postoperative day, according to another scale. The patients who had had a total joint replacement and who controlled the analgesia walked farther on the first postoperative day than those who received intramuscular injections. There were no significant differences between the two groups with regard to the rate of complications, the arterial oxygen saturation levels during the first twenty-four hours after the operation, or the length of stay in the hospital. The nursing staff preferred the patient-administered method of analgesia, as it necessitated equal or less nursing time to assemble, initiate, and maintain than traditional intramuscular injections. The average cost per patient was $58.58 for the patient-administered analgesia and $22.45 for the intramuscular injections.(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare the use of patient-controlled analgesia to intermittent intramuscular injections of morphine following major gynecological laparoscopic procedures in order to assess differences in level of pain, sedation, episodes of nausea and/or vomiting, hospitalization time and patient satisfaction with their postoperative analgesia.\n Seventy-two patients undergoing major gynecological laparoscopic surgery were randomized to receive either postoperative analgesia via intermittent intramuscular injection of morphine (Group 1) or patient controlled analgesia (PCA-Group 2). All patients received anesthesia via a standardized protocol. Postoperative pain levels were recorded via a 10 cm visual analogue scale, and sedation scores were recorded on a standard PCA form. Episodes of nausea and vomiting were also recorded on the same form.\n There were no statistically significant differences between intramuscular analgesia and PCA for any of the factors studied. Most significantly it was found that most patients ceased to require either form of parenteral analgesia within 24 hours of their procedure, regardless of the operating time.\n It is important for the surgeon to be aware of the effects of postoperative analgesia on his or her patients' level of satisfaction. We do not recommend the use of PCA analgesia following major laparoscopic gynecological surgery.", "Two pumps, 'PA' and 'PB,' with different drug delivery characteristics were available at the time of this study for patient-controlled analgesia (PCA). PB purportedly produces a 'placebo effect' by emitting an audible signal whenever the patient depresses the trigger button. PA emits an audible signal only when the drug is successfully administered into the patient's intravenous line. In a prospective, randomized Latin squares cross-over study, the 2 pumps and conventional therapy were compared for efficacy and cost. Patients in both pump groups used less drug and perceived less pain than those on conventional therapy. However, statistically less anxiety and greater pain relief and patient and nursing satisfaction were reported with PA only. Daily cost including drug, pharmacy and nursing time, pump rental was 33%, PA, versus 23%, PB, more than conventional therapy. Purchase and amortization of the pumps decreases the cost. We conclude that PCA provides superior pain management at minimal additional cost.", "This study was conducted in order to investigate the advantages and limitations of four analgesic modalities: a) epidural morphine; b) intravenous morphine; c) patient controlled intravenous morphine (patient-controlled analgesia); and d) non-steroidal anti-inflammatory drugs. Eighty patients undergoing major abdominal surgical procedures were prospectively and randomly treated with one of the above-mentioned analgesic methods. Evaluation of pain perception was done using the visual analogue pain score and the simple descriptive scale 4 hours after the procedure, in the early morning on postoperative day 1 and in the afternoon on postoperative days 1, 2 and 3. The need for supplementary analgesia and the onset of complications, if any, were also evaluated for each patient. Patient-controlled intravenous morphine yielded the best analgesic effect over the entire period. Epidural morphine was more effective in the very early postoperative period compared to modalities (b) and (d). Non-steroidal anti-inflammatory drugs, on the other hand, were more effective on the later postoperative days. None of the patients in group C needed supplementary analgesia, as against 20% in group A, 55% in group B and 40% in group D. Patients with hypochondriasis scores > 70 or depression scores > 70 required supplementation of analgesia more often. Morphine proved to be the drug of choice. Drug titration may be modulated in relation to the psychological characteristics of the patient. The best drug titration modality, in fact, is patient-controlled analgesia.", "Forty patients recovering from upper abdominal surgery were allocated randomly to receive i.m. morphine 0.15 mg kg-1 as required or patient-controlled analgesia (PCA), with i.v. morphine 1 mg and a 5-min lock out time. Arterial oxygen saturation (SpO2) was measured continuously the night before and for 24 h immediately after surgery. A significantly greater proportion of patients in the PCA group (nine of 19) rated their analgesia as excellent compared with the i.m. group (two of 20) (P < 0.05). There was no significant difference in the incidence of postoperative hypoxaemia in the two treatment groups. Severe postoperative hypoxaemia (SpO2 < 85% for more than 6 min h-1) was seen in three patients receiving i.m. analgesia and one patient in the PCA group.", "A statistical model was developed: 1) to compare the efficacy of patient-controlled analgesia (PCA) and traditional intramuscular (IM) opioids for pain relief in 40 patients after total knee replacement and, 2) to evaluate pain cycles associated with each technique. Hourly visual analog pain scores were subjected to two-way analysis of variance (ANOVA) and time-series analysis. Hourly verbal analog pain scores were used to determine predominant pain levels. According to ANOVA, PCA was no more effective than were IM opioids. Time-series analyses documented a complete cycle of pain every 5.3 hours in patients receiving IM opioids but no pain cycle with use of PCA. Analysis of PCA verbal analog scores demonstrated self-administration of opioids to \"moderate\" levels of pain relief with use of PCA, not to complete analgesia. These results suggest that certain patients may not envision complete postoperative analgesia as being possible. Hence, they self-administer opioids for pain relief with PCA according to their expectations. Population characteristics may modify PCA efficacy. These characteristics should be delineated and the use of PCA targeted to appropriate patients.", "The pharmacy and nursing time requirements, quality of postoperative pain control, and cost of patient-controlled analgesia (PCA) and intramuscular (i.m.) analgesic therapy were studied. All timings were conducted with a stopwatch on a single nursing unit that primarily receives gynecologic surgery patients. The various work elements involved in each type of therapy were timed individually. Both quality of analgesia and cost were evaluated in a prospective, randomized study in hysterectomy patients. I.M. patients received meperidine hydrochloride 75-100 mg every three to four hours as needed. PCA patients had access to morphine sulfate 1 mg or meperidine hydrochloride 10 mg, with a six-minute lockout period. The patients scored their pain every four hours. Direct costs for PCA were calculated as drug cost plus tubing cost plus form cost plus maintenance cost plus depreciation cost. Direct costs for i.m. therapy consisted of the cost of drugs. The total mean nursing time per patient was 16.9 minutes for PCA and 10.7 minutes for i.m. therapy. Pharmacy time per patient was 5.1 minutes longer for PCA than for i.m. therapy. Thirty-six hysterectomy patients (17 i.m. and 19 PCA) were enrolled in the study of pain control and cost. Among i.m. patients, 64% of the pain scores were mild or worse, compared with 40% for PCA patients. The median pain scores were moderate for i.m. patients and mild for PCA patients. Scores tended to be lower for PCA patients at 16 and 20 hours. Although equal numbers of patients in the two groups experienced nausea, i.m. patients needed more doses of antiemetics than PCA patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "We have performed a prospective randomised trial of 30 patients undergoing craniotomy to compare intramuscular codeine phosphate with patient-controlled analgesia using morphine 1 mg bolus with a 10-min lockout and no background infusion. For 24 h postoperatively, pain, nausea, Glasgow coma score, respiratory rate and sedation score were assessed. There was a wide variation in the amounts of morphine requested by the patients in the patient-controlled analgesia group in the first 24 h postoperatively (range 2-79 mg, median 17 mg). There was a small, but non-significant, reduction in pain scores in the patient-controlled analgesia group. There were no significant differences between the two groups in respect of nausea and vomiting, sedation score or respiratory rate. No major adverse effects were noted in either group. Patient-controlled analgesia with morphine is an alternative to intramuscular codeine phosphate in neurosurgical patients which merits further investigation.", "A prospective comparison of conventional analgesia and patient-controlled analgesia using morphine was conducted. Each patient underwent a major gynecologic oncology procedure and was observed on the post-operative floor. All 192 patients were studied during the first three post-operative days. The findings suggest less total medication and less sedation with equal pain control in the patient-controlled analgesia group.", "There are no comparisons of i.v. patient controlled analgesia (i.v. PCA) versus nurse-administered subcutaneous (NA s.c.) morphine for acute postoperative pain. We undertook a prospective, randomized, controlled clinical trial of 80 cardiac surgical patients to compare i.v. PCA with NA s.c. morphine for postoperative pain control. Visual analog scale (VAS) pain scores at rest and with movement, daily verbal pain relief scores, and side effect profiles were not significantly different. Total morphine requirements in the two groups were not significantly different. A physiotherapist's evaluation of the effectiveness of analgesia for chest physiotherapy revealed no difference between the two groups. We conclude that NA s.c. morphine, administered as required (up to hourly), is a satisfactory alternative to i.v. PCA morphine after cardiac surgery. Implications: In a prospective, randomized study, we have shown that nurse-administered subcutaneous morphine is a satisfactory alternative to i.v. patient-controlled analgesia after cardiac surgery.", "nan", "Previous studies have shown that patient-controlled analgesia (PCA) provides effective pain control in the postoperative patient. To determine the impact of PCA technology on the overall hospital course, we designed a randomized controlled study comparing patients receiving analgesia using PCA infusion (Abbott Lifecare, Abbott Laboratories; Chicago, IL) with patients receiving analgesia by traditional intramuscular or intravenous methods. All patients had undergone elective cholecystectomy. Sixty-nine patients completed the study, 35 received traditional postoperative analgesia, and 34 received analgesia using the PCA infuser. Comparison of both groups demonstrated no significant difference in postoperative bowel activity with both groups receiving liquids on the first postoperative day. There was no significant difference between the two groups with respect to postoperative length of stay (3.4 days for PCA vs 3.6 days for traditional). Patients demonstrated a wide range of analgesic requirement in the first 24 hours but the average of the total analgesic required was higher in the PCA group (average, 29.5 mg) than the traditional group (22.8 mg). Urinary complications occurred more commonly in the group of patients receiving traditional analgesia than in the group of patients receiving analgesia with the PCA device. When compared with patients receiving analgesia by traditional methods, patients receiving the PCA infusion required more analgesia with fewer urinary complications and similar postoperative length of stay.", "To determine whether the use of patient-controlled analgesia vs intramuscular injections improves postoperative psychological parameters, particularly anxiety.\n Randomized, controlled trial of patient-controlled analgesia vs as-needed intramuscular morphine with pre- and postoperative assessments of pain, mental status, narcotic use, anxiety and mood states.\n General surgical wards and surgical intensive care unit at a Veterans Administration hospital.\n Eighty-three elderly, chronically ill males undergoing major elective surgery.\n Subjects randomized to receive postoperative patient-controlled analgesia vs as-needed intramuscular morphine. Pre- and postoperative assessments of State-Trait Anxiety Inventory, McGill-Dartmouth Part IV and Short Portable Mental Status Questionnaire. Pain (using linear analog scale), sedation score and narcotic use assessed every 4 hours for 72 hours.\n No differences were found in state anxiety or self-perceived mood states. Postoperative state anxiety was found to relate most closely to preoperative anxiety and postoperative complications, rather than method of analgesia or severity of pain. However, patient-controlled analgesia subjects had significantly improved analgesia and increased satisfaction.\n The use of patient-controlled analgesia does not significantly alter the measured psychological parameters, compared with intramuscular injections. Improved analgesia is the result of pharmacologic effects, independent of psychological factors.", "nan", "The patients received thoracotomy usually suffered from significant severe pain postoperatively, which accompanied with impaired pulmonary function or increased incidences of atelectasis and pneumonia. So adequate analgesia for those patients is indicated. The purpose of this study is to investigate the efficiency of patient-controlled analgesia (PCA) and determine whether it is better than conventional analgesia or not. Twenty-six patients, ASA physical status class I and II, were randomized into two groups: PCA and intramuscular (IM). The effect on pain relief was assessed by a visual analogue pain scale (VAPS) q 4 h postoperatively for two days. Forced vital capacity (FVC) and the questionnaire of nocturnal sleep disturbance by pain were evaluated preoperatively, the first, second postoperative mornings. As result of this study, the patients of PCA group get less pain than IM group after the first and second days of surgery. VAPS values are 3.7 +/- 1.1, 2.8 +/- 0.8 and 6.1 +/- 0.9, 5.3 +/- 1.1 respectively pertaining to PCA and IM groups (p less than 0.05). The patients of IM group get more disturbance of nocturnal sleep than PCA group at initial two nights of postoperation as well (p less than 0.05). It is manifest to look out the significant difference between these two groups in accordance with FVC ratio records of post-surgery vs presurgery at initial two days after surgery on the subject of respiratory function recovery. PCA group are 46.46 +/- 7.29%, 52.25 +/- 8.32% in a condition of more progress on lung function recovery than IM group of 38.13 +/- 10.25%, 42.15 +/- 7.82% (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)", "A randomized, controlled clinical trial was conducted on 72 patients undergoing elective cardiac surgery to compare patient-controlled analgesia (PCA) to nurse-titrated infusion of morphine. Pain and nausea scores were assessed at 5, 20, 32 and 44 hours after cardiopulmonary bypass. Serum cortisol estimations were performed at 24 and 48 hours, and morphine consumption was measured at 0-24 and 24-48 hours. There was no difference between pain scores (P = 0.72), nausea scores (P = 0.52), serum cortisol at 24 and 48 hours (P = 0.32 and P = 0.34), and morphine consumption at 0-24 and 24-48 hours (P = 0.16 and P = 0.12). There was also no difference in the time to tracheal extubation (P = 0.79) and discharge from ICU (P = 0.64). There was a significant association between pain and serum cortisol at 48 hours (P = 0.023). This study also found a tenfold difference in the amount of morphine used (range = 11 to 108 mg), with no significant association with patient age or sex. We could find no significant benefit from the routine use of PCA in cardiac surgical patients.", "To compare standard nurse-based pain therapy with a patient-controlled analgesia (PCA) regimen.\n Prospective, randomized study.\n Single-institutional, clinical investigation in an urban, university-affiliated hospital.\n Sixty patients undergoing elective first-time cardiac surgery were included.\n In 30 patients, a standard analgesic regimen was used, and in 30 patients, a PCA regimen was used. The perioperative and postoperative management was similar for all patients.\n Degree of sedation, satisfaction, and pain (by visual analog scale [VAS]) was assessed within the first 3 postoperative days. Vital capacity (VC) and forced expiratory volume in 1 second (FEV1) were measured using a portable spirometry system. Cortisol and troponin T (TnT) plasma levels were also measured. The expectation of pain was similar in both groups, and the postoperative pain score was significantly lower in the PCA than in the standard group throughout the study period. Significantly more piritramid was used in the PCA (total, 75.6 +/- 33.4 mg) than in the standard group (total, 20.1 +/- 31.9 mg). VC and FEV1 were significantly lower in the standard group compared with the PCA patients. Cortisol and TnT plasma levels were similar in both groups. Frequency of side effects were similar for both groups.\n Because of the beneficial effects with regard to degree of pain and satisfaction, pain management using PCA systems can be recommended for cardiac surgery patients. It appears to be superior to standard nurse-based pain therapy.", "The present study examined the impact of two methods of pain management on recovery in 38 women undergoing hysterectomy. One group received IV morphine in the recovery room and IM morphine on the ward on a PRN basis (PRN group). In the other group, a loading dose of morphine 8 mg IV was given when the patient first complained of pain and patient-controlled IV morphine (PCA) was initiated and continued for 48 h (PCA group). Both groups received similar amounts of morphine overall, differently distributed over time. The PCA patients received 8 mg.h-1 in the recovery room (approximately 2.5 hrs) and less thereafter. The PRN patients received approximately 2 mg.h-1 for the entire 48-hr period. Pain control was better throughout convalescence and less variable across time with PCA management. Minute ventilation also recovered faster and by day four was 25 per cent above the preoperative baseline in the PCA group. In addition, oral temperature became normal one day earlier, ambulation recovered more rapidly and patients were discharged from hospital earlier. The data suggest that early treatment with relatively high, self-titrated morphine doses may alter the course of the metabolic response to surgery.", "We have evaluated the level of state and trait anxiety, neuroticism, extroversion and coping style as predictors of the effectiveness of patient-controlled analgesia (PCA) in 110 patients undergoing total abdominal hysterectomy. After operation patients were allocated to receive pain control with either PCA or i.m. injections (IMI). Pain was assessed using the short form McGill pain questionnaire at 6, 18 and 24 h after operation, and by recording the amount of analgesic consumed in the first 24 h after surgery. Both state anxiety and coping style were significant predictors of postoperative pain, irrespective of the method of analgesia used. Patients using PCA experienced significantly better pain control than those receiving IMI. However, it was those with high levels of state anxiety who experienced the greatest reduction in pain with PCA. In addition to achieving better pain control, patients who received PCA used significantly less analgesia and were discharged earlier than patients who received IMI.", "nan", "Patient-controlled analgesia (PCA) offers effective postoperative pain management. However, the evidence of economic benefits associated with its use is lacking. Although suggestive, the potential economic advantages of PCA in saving nursing time and shortening hospital stay need objective documentation.\n This study compared the effects of morphine administered by PCA systems with intramuscular (i.m.) morphine injection on patient analgesic response, satisfaction, nursing time requirements, and postoperative recovery in 23 patients undergoing \"open\" cholecystectomy and 44 patients undergoing lumbar laminectomy and bony fusion. After the operation, patients in the PCA group received 1.5-2 mg morphine with a lockout of 5-10 minutes on demand, whereas those in the i.m. group received 0.15-0.2 mg/kg every 4 hours on demand. Visual analog scale (VAS) pain scores and satisfaction scores were evaluated at 4-hour intervals while nursing time spent on both analgesia-related and non-analgesia-related activities was recorded continuously by a team of independent observers on the ward. Recovery time profile for the return of bowel function, activities of daily living, ambulation without support, and length of hospital stay was also recorded.\n It was found that morphine consumption, VAS, and satisfaction scores were similar in both PCA and i.m. treatment groups following both types of surgery. However, the delay in nurse response to i.m. morphine request ranged from 27.2 +/- to 42.1 +/- 11.8 minutes. The demand of nursing time on analgesia administration was less with PCA. The magnitude of time saving was 10 min/patient/d in cholecystectomy patients and 13 min/patient/d in laminectomy patients. The speed of postoperative patient recovery was similar between the two analgesia groups. Length of hospital stay following cholecystectomy was shorter--92.0 +/- 5.9 hours with PCA versus 128.6 +/- 22.2 hours with i.m. (not statistically significant)--whereas that following laminectomy was not different.\n Data in this study have demonstrated some beneficial effects of PCA on nursing time requirements when it was used following cholecystectomy and lumbar laminectomy at the University of Toronto: however, the magnitude of these benefits was less than previously reported. The effects of PCA on postoperative recovery and hospital stay, however, were not significantly different from i.m. therapy.", "We conclude that the intravenous PCA method is a cost-effective technique. Although the PCA device is expensive, the cost-effectiveness analysis should give explicit figures for physicians and the hospital administrators to decide whether they should use the PCA instead of the conventional method.", "In the current study, 55 patients undergoing elective cholecystectomy were randomly allocated to receive postoperative analgesia (morphine sulfate) administered through either patient-controlled intravenous (PCA) or standard intramuscular (IM) routes. There were no significant differences in length of hospitalization or required dose of morphine sulfate. Patients randomized to PCA reported significantly improved subjective relief from pain and a smaller percentage of time in pain during each of the first two postoperative days. In addition, they reported less sedation and less interference with both postoperative breathing and pulmonary recovery than patients who received IM morphine. Theoretically, PCA regimens can deliver narcotic analgesia at a higher and more varied rate (with fewer side effects) compared with standard IM narcotic delivery, which is more limited by considerations of clinical doses. In PCA dosing, patients should experience less time in pain and sedation. The results of the current study support this premise.", "Patient-controlled analgesia (PCA) with intravenous pethidine was compared with nurse-controlled pethidine infusions for pain relief in 200 patients after major abdominal or thoracic surgery. Pain, level of sedation, nausea and presence of other adverse effects, in addition to cumulative pethidine requirement, were measured for the first 24 hours after surgery. Both groups were similar for age, weight and type of surgery. There was no significant difference between the quality of analgesia achieved in both groups. The frequency and severity of adverse effects was also similar. The cumulative pethidine dose administered to both groups was identical. It is concluded that nurse-controlled opioid infusions are as effective as PCA and may be used as an alternative to PCA where this is either unavailable or unsuitable.", "A clinical trial compared the efficacy of a mechanical device to deliver patient-controlled analgesia (PCA) (n = 25) with intramuscularly administered morphine (n = 17) for postcesarean pain management. Hypotheses were: (1) patient-controlled administration of narcotics will be superior (increased satisfaction, reduced pain, decreased sedation, increased ambulation, decreased length of stay), and (2) functional vital capacity will increase post-operatively with PCA. No differences in demographic variables were identified (P = less than or equal to .001). Differences in satisfaction (greater in PCA group, P = less than or equal to .05), ambulation (greater in PCA group, P = less than or equal to .001), amount of medication used (greater in PCA group, P = less than or equal to .001), and sedation level (less in PCA group, P = less than or equal to .05) were identified. No differences in vital capacity were identified. The hypothesis related to the superiority of PCA was accepted, while the association between PCA and increased vital capacity was not supported. The use of mechanical PCA devices provides an effective and safe means of managing postcesarean pain.", "The goal of this study was to evaluate the effectiveness on postoperative pain, and cognitive impact, of patient-controlled analgesia (PCA) compared with subcutaneous (s.c.) injections of morphine in elderly patients undergoing total hip replacement (THR).\n Forty patients older than 70 yr were randomly assigned to two different postoperative analgesic techniques for 48 h: i.v. PCA morphine (dose, 1 mg; lockout interval, 8 min; PCA group) or regular s.c. morphine injections (SC group). Postoperative pain was assessed at rest and when moving, using a visual analogue scale (VAS) every 4 h. A Mini Mental Status (MMS) examination was used to assess cognitive functions before surgery, at 2 h, 24 h and 48 h after surgery, and at hospital discharge. Side-effects were also recorded systematically during the first 48 h after surgery.\n The PCA group showed significantly lower pain scores than the SC group both at rest and during mobilization. However, the clinical significance of pain scores was weak. There was no intergroup difference in postoperative MMS scores. The incidence of side-effects was similar in both groups.\n We conclude that in healthy elderly subjects undergoing THR, the flexibility of the analgesic regimen is more important than the route of administration with regard to efficacy, adverse effects and recovery of cognitive function.", "A randomized, controlled clinical trial was conducted on 66 patients undergoing elective cardiac surgery to compare patient-controlled analgesia (PCA) to nurse-controlled analgesia (NCA) with continuous morphine infusion. Hourly assessment of pain (at rest and on movement) using a visual analogue scale (VAS), of respiratory rate, and level of sedation took place for the 24 h following extubation. The incidence of nausea was also recorded. Mean pain scores were calculated, and peak pain and sedation scores, together with lowest respiratory rates, were identified. Morphine consumption was measured at 24 h. No significant differences were found between the groups' scores for pain or sedation. The PCA group had significantly lower respiratory rates (P = 0.02) and a lower incidence of nausea (P = 0.008). The PCA group also consumed significantly more morphine (P = 0.0001). The study suggests a beneficial effect from PCA after cardiac surgery in reducing nausea, compared to NCA. It confirms nurse-controlled infusion analgesia as an effective form of pain relief in an intensive care and high-dependency setting." ]

[ "9572419", "15154088", "3119647", "16169399" ]

[ "Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: a randomized, double-blind, placebo-controlled, clinical trial.", "Effect of follicle-stimulating hormone on sperm quality and pregnancy rate.", "Treatment of severe oligospermia with human chorionic gonadotropin/human menopausal gonadotropin: a placebo-controlled, double blind trial.", "Treatment of male idiopathic infertility with recombinant human follicle-stimulating hormone: a prospective, controlled, randomized clinical study." ]

[ "To examine the role of recombinant human follicle stimulating hormone (rhFSH) in male idiopathic infertility a randomized, double-blind, placebo-controlled study was performed. Of 211 patients screened, 67 were finally included. After two pre-examinations, patients were randomized and treated for 12 weeks, either with 150 IU rhFSH or with placebo. Examinations (physical examination, scrotal ultrasonography, semen analysis, hormone measurements, and in 31 patients electron microscopy (EM) of spermatozoa were performed 6 and 12 weeks after treatment initiation and 6 and 12 weeks after completion of treatment. Pregnancies were recorded for a further 3 months after the last examination. Of the 67 patients included in the study, 34 treated and 31 placebo patients could be analysed. In the treated group, FSH was elevated compared to baseline values (P < 0.001). At the end of treatment testicular volume in the treated group was increased compared to placebo (P < 0.05) and baseline (P < 0.001). Apart from an increase in sperm motility (P < 0.05) in the placebo group and in sperm DNA condensation (P < 0.001) in the treated group no significant changes were observed in semen parameters. Two spontaneous pregnancies in partners of men in the treated group and none in the placebo group occurred. However, two pregnancies occurred in partners of men in the placebo group induced by intrauterine insemination or intracytoplasmic sperm injection. In conclusion, at the chosen dose and duration, rhFSH did not lead to an improvement of conventional or EM sperm parameters nor to an increase in pregnancy rates. However, the increased testicular volume and sperm DNA condensation give reason for further investigations.", "To evaluate the possible links between ultrastructural sperm quality and the clinical pregnancy rate in infertile males treated with FSH before intracytoplasmic sperm injection (ICSI).\n Forty-four infertile males with idiopathic oligo-asthenozoospermia were randomly allocated to the treated (n=24) and non-treated (control, n=20) groups. Semen analysis was carried out by light and transmission electron microscopy (TEM) before and 12 weeks after FSH therapy. ICSI was performed in all couples.\n TEM revealed a significant improvement in sperm quality after FSH treatment, particularly in men with their partners achieving clinical pregnancy. The pregnancy rate was 33 % in the treated group and 20 % in the control.\n RESULTS highlight a positive role of FSH therapy in infertile males before ICSI, which was correlated with an increased pregnancy rate in treated couples. We believe that improved sperm ultrastructure after FSH therapy could positively influence the quality and early stage of embryo development, thereby increasing the probability of embryo implantation.", "In an effort to evaluate the effect of hCG/human menopausal gonadotropin (hMG) treatment on semen parameters in normogonadotropic men suffering from oligospermia, a double blind, placebo-controlled study was conducted. After 2 basal examinations of seminal parameters and reproductive hormones, 39 men were recruited for the trial. Nineteen men, allocated randomly to the active drug group, received im injections of 2500 IU hCG twice a week in combination with 150 IU hMG three times a week for 13 weeks, while 20 men were treated, following the same injection schedule, with NaCl only. After the 13-week treatment period, follow-up examination was performed, followed by 3 additional examinations at 4-week intervals. Of those men receiving hCG-hMG, 2 induced pregnancies in their wives, while no pregnancies were reported in the placebo group. Sperm concentrations, the percentages of motile sperm, and the proportions of normally formed spermatozoa, however, were similar in the 2 groups at all times. It was not possible to predict the outcome of treatment based on results of GnRH and hCG tests performed before the treatment phase.", "To evaluate the effects of treatment with FSH on seminal parameters and spontaneous pregnancy in male infertility.\n Prospective, controlled, randomized clinical study.\n Infertility center at a university hospital.\n One hundred twelve men affected by idiopathic oligozoospermia.\n Patients were randomized into two groups: 62 subjects were treated with 100 IU of recombinant human FSH on alternate days for 3 months, and 50 patients did not receive any treatment. Semen analysis was performed in all subjects at the end of this period of treatment and after the following 3 months. Subjects who had not reached spontaneous pregnancy underwent assisted reproductive techniques.\n Seminal parameters, testicular cytologic analysis, FSH, LH, T, and inhibin B concentrations.\n The treatment group considered as a whole did not show modifications in sperm parameters. However, a subgroup of these (30, 48.4%) had a significant increase of sperm count (responder group). In the period including 3 months after the withdrawal of FSH therapy, we observed a significantly higher spontaneous pregnancy rate in the responder group (5 of 30 [16.7%]) with respect to nonresponder and nontreated groups (1 of 32 [3.1%] and 2 of 50 [4.0%], respectively). Furthermore, the improvement of seminal parameters in the responder group allowed these patients to undergo less frequent IVF-ET/intracytoplasmic sperm injection.\n Results from this controlled, randomized clinical trial show that FSH therapy does not improve sperm concentration or pregnancy rate when infertile male patients are chosen solely by the clinical criteria of idiopathic oligospermia and normal FSH concentration. Subgroup analysis, however, does indicate that patients without maturation arrest in addition to the clinical scenario do benefit from medical therapy." ]

[ "7377606", "4932953", "6329021" ]

[ "Patient acceptance of orally administered antacid therapy during labor.", "A double-blind comparison of the anti-emetic effect during labour of metoclopramide and perphenazine.", "Oral ranitidine in labour." ]

[ "nan", "nan", "Ranitidine 150 mg orally was given every 6 hours to 909 women in labour, while a control group of 378 women received conventional alkali therapy. No differences in incidences of operative intervention, placental retention or post-partum haemorrhage were observed between groups. Gastric sampling during emergency anaesthesia revealed a pH less than 2.5 in four of 51 women who received ranitidine and in two of 31 women who received magnesium trisilicate. Gastric volumes were slightly lower (mean 83 ml) in the study group than in the control group (mean 122 ml). Absorption of ranitidine was greatly slowed following narcotic administration and gastric volume was significantly higher in those patients given narcotics in labour. Apgar scores were similar in both groups of infants, and babies whose mothers were given ranitidine showed no delay in achieving high gastric acidity and no increase in bacterial colonization of the gastro-intestinal tract. Low levels only of ranitidine were found in the blood of babies at 2-3 hours and approximately 12 hours after birth." ]

[ "8839553", "2405271", "8498838" ]

[ "A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis.", "A randomized trial of surgery in the treatment of single metastases to the brain.", "Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery?" ]

[ "Cerebral metastasis is a common oncologic problem that occurs in 15-30% of cancer patients; approximately half such metastases are single. Previous retrospective studies and two randomized trials reported that the addition of surgical extirpation prior to radiation therapy increased survival, neurologic function, and quality of life compared with radiation alone in patients with a single brain metastasis.\n A randomized controlled trial was conducted in which patients with a single brain metastasis were allocated to undergo radiation alone or surgery plus radiation. Radiation consisted of 3000 centigray to the whole brain in 10 fractions.\n Forty-three patients received radiation alone and 41 patients surgery plus radiation. All but two of the study patients died. No difference in survival was detected between the groups; the median survival for the radiation group was 6.3 months (95% confidence interval, 3-11.4) compared with 5.6 months for the surgery plus radiation group (95% confidence interval, 3.9-7.2) (P = 0.24). Most patients died within the first year (69.8% in the radiation arm vs. 87.8% in the surgery plus radiation arm). There were no significant differences in the 30-day mortality, morbidity, or causes of death. Extracranial metastases was an important predictor of mortality (relative risk, 2.3). The mean proportion of days that the Karnofsky performance status was > or = 70% did not differ between the 2 groups.\n This trial failed to demonstrate that the addition of surgery to radiation therapy improved outcome of patients with a single brain metastasis. Thus, the efficacy of surgery plus radiation compared with radiation alone needs to be addressed by further clinical trials and/or a meta-analysis.", "To assess the efficacy of surgical resection of brain metastases from extracranial primary cancer, we randomly assigned patients with a single brain metastasis to either surgical removal of the brain tumor followed by radiotherapy (surgical group) or needle biopsy and radiotherapy (radiation group). Forty-eight patients (25 in the surgical group and 23 in the radiation group) formed the study group; 6 other patients (11 percent) were excluded from the study because on biopsy their lesions proved to be either second primary tumors or inflammatory or infectious processes. Recurrence at the site of the original metastasis was less frequent in the surgical group than in the radiation group (5 of 25 [20 percent] vs. 12 of 23 [52 percent]; P less than 0.02). The overall length of survival was significantly longer in the surgical group (median, 40 weeks vs. 15 weeks in the radiation group; P less than 0.01), and the patients treated with surgery remained functionally independent longer (median, 38 weeks vs. 8 weeks in the radiation group; P less than 0.005). We conclude that patients with cancer and a single metastasis to the brain who receive treatment with surgical resection plus radiotherapy live longer, have fewer recurrences of cancer in the brain, and have a better quality of life than similar patients treated with radiotherapy alone.", "Most patients treated for single or multiple brain metastases die from progression of extracranial tumor activity. This makes it uncertain whether the combination of neurosurgery and radiotherapy for treatment of single brain metastasis will lead to better results than less invasive treatment with radiotherapy alone. The effect of neurosurgical excision plus radiotherapy was compared with radiotherapy alone in a prospectively randomized trial with 63 evaluable patients with systemic cancer and a radiological diagnosis of single brain metastasis. Radiotherapy was given to the whole brain by a novel scheme of 2 fractions per day of each 2 Gy for a total of 40 Gy. Before randomization, patients were stratified by site (lung cancer vs nonlung cancer) and status of extracranial disease (progressive vs stable). Survival as such and functionally independent survival (FIS; defined as World Health Organization performance status < or = 1 and neurological function < or = 1) were compared between both treatment arms. The combined treatment compared with radiotherapy alone led to a longer survival (p = 0.04) and a longer FIS (p = 0.06). This was most pronounced in patients with stable extracranial disease (median survival, 12 vs 7 mo; median FIS, 9 vs 4 mo). Patients with progressive extracranial cancer had a median overall survival of 5 months and a FIS of 2.5 months irrespective of given treatment. Improvement in functional status occurred more rapidly and for longer periods of time after neurosurgical excision and radiotherapy than after radiotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "16940689", "15309229", "5443334", "3891946", "18971491", "3881731", "19043499", "5806247" ]

[ "Effect of prophylactic phototherapy on neonatal hyperbilirubinemia of prematures.", "[Evaluation of two guidelines for the management of hyperbilirubinemia in newborn babies weighing less than 2,000 g].", "Phototherapy and hyperbilirubinemia of the premature.", "Randomized trial of prophylactic phototherapy in the infant with very low birth weight.", "Aggressive vs. conservative phototherapy for infants with extremely low birth weight.", "Efficacy of phototherapy in prevention and management of neonatal hyperbilirubinemia.", "A randomized trial of aggressive versus conservative phototherapy for hyperbilirubinemia in infants weighing less than 1500 g: Short- and long-term outcomes.", "Effect of environmental illumination in prevention of hyperbilirubinemia of prematurity." ]

[ "nan", "To evaluate the use of two phototherapy guidelines for the treatment of hyperbilirubinemia in newborn babies weighing less than 2,000 g.\n Eighty-one newborn infants with birth weight less than 2,000 g were studied. They were divided in two groups: the \"early\" group, which started phototherapy 12 hours after birth, undergoing treatment for at least 96 hours; and the \"late\" group, which received phototherapy whenever the transcutaneous bilirubin reached 8 mg/dl and phototherapy suspended when bilirubin levels fell to 5 mg/dl. The following factors were analyzed: maintenance of transcutaneous bilirubin levels below 10 mg/dl, mean value of daily transcutaneous bilirubin, the highest transcutaneous bilirubin value and the period it first occurred, and duration of treatment.\n In the early group, 20% of all patients showed transcutaneous bilirubin level higher than 10 mg/dl compared to 60% of patients in the late group. The highest daily mean rate of transcutaneous bilirubin in the early group was 6.6 mg/dl, which happened on the 7th day. In the late group, it was 8.6 mg/dl on the 2nd day after birth. The median duration of phototherapy treatment used in the early group was 96 hours (minimum of 96 and maximum of 156 hours) and in the late group, 51 hours (minimum of zero and maximum of 120 hours). None of the babies needed changes in the treatment (double phototherapy or exchange transfusion).\n The use of early phototherapy treatment for babies weighing less than 2,000 g is safer when compared to the late group, considering satisfactory the maintenance of transcutaneous bilirubin levels below 10 mg/dl.", "nan", "Twenty-two preterm infants (birth weight 850 +/- 220 gm) were randomly assigned to receive phototherapy either soon after birth or after the serum bilirubin concentration reached 5 mg/dl. Infants receiving prophylactic phototherapy were placed under lights at a significantly earlier age and lower serum bilirubin concentration than infants in the routine group (P less than 0.001). There was no significant difference between groups in peak serum bilirubin concentration, age at which it peaked, rate of rise in serum bilirubin concentration, or serum bilirubin concentration at any time during the study. Infants assigned to the prophylactic phototherapy group were under lights for a significantly longer time than those in the routine group (P less than 0.05). There was a significant rise in both configurational and structural photo-isomers (P less than 0.005) independent of serum bilirubin concentration after phototherapy in all patients. These data suggest that the clinical course of hyperbilirubinemia is not altered in infants with very low birth weight receiving prophylactic phototherapy compared with infants with phototherapy begun at a bilirubin concentration of 5 mg/dl.", "It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less).\n We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments.\n Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g.\n Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.)\n 2008 Massachusetts Medical Society", "nan", "Treatment regimens for hyperbilirubinemia vary for very low birth weight infants. The present study seeks to determine whether the initiation of conservative phototherapy is as effective as aggressive phototherapy in reducing peak bilirubin levels without increasing adverse effects.\n The present randomized, controlled study included infants with birth weights between 500 g and 1500 g, stratified into two birth weight groups. In one group, aggressive phototherapy was commenced by 12 h of age, while in the other group, conservative phototherapy was commenced if serum bilirubin levels exceeded 150 mumol/L. The primary outcome variables were peak serum bilirubin levels and hours of phototherapy. Secondary outcomes were age at peak bilirubin levels, number of infants with rebound hyperbilirubinemia, and number of adverse short- and long-term outcomes.\n Of 174 eligible infants, 95 consented to participate -49 in the conservative arm and 46 in the aggressive arm. Ninety-two infants completed the study. There was no significant difference in peak bilirubin levels except in infants who weighed less than 1000 g -171.2+/-26 mumol/L (conservative) versus 139.2+/-46 mumol/L (aggressive); P<0.02. There was no difference in duration of phototherapy or rebound hyperbilirubinemia. There were no differences in short-term adverse outcomes. Of the 87 infants who survived until hospital discharge, 82 (94%) had some follow-up and 75 (86%) attended follow-up until 18 months corrected age. The incidence of cerebral palsy, abnormal mental developmental index at 18 months corrected age, or combined outcome of cerebral palsy and death did not significantly differ between the two groups.\n In infants weighing less than 1000 g, peak bilirubin levels were significantly higher using conservative phototherapy regimens and there was a tendency for poor neurodevelopmental outcome.", "nan" ]

[ "9713447", "18310480", "15229100", "2068695", "9517606", "8564107", "10379018", "18778120", "12570112", "12583942", "14680078", "15946834", "17314337", "19014549", "9519948", "10359405", "9925060", "2180105", "11587988", "17557771", "8625660", "11217907", "9364183", "12149529", "19841453", "3465581", "20037682", "19378223", "7497762", "14682412", "10556133", "1412119", "12970006", "10421835", "10807619", "10095821", "12391509", "15363007", "12070058", "21917440", "10343624", "1489129", "15741434", "11136260", "10581660", "12379552", "15894479" ]

[ "Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease.", "The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease.", "Effects of fluticasone on systemic markers of inflammation in chronic obstructive pulmonary disease.", "Effects of inhaled budesonide on spirometric values, reversibility, airway responsiveness, and cough threshold in smokers with chronic obstructive lung disease.", "Short-term treatment with budesonide does not improve hyperresponsiveness to adenosine 5'-monophosphate in COPD.", "Effect of fluticasone propionate on sputum of patients with chronic bronchitis and emphysema.", "Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease.", "Efficacy and safety of budesonide and formoterol in one pressurized metered-dose inhaler in patients with moderate to very severe chronic obstructive pulmonary disease: results of a 6-month randomized clinical trial.", "Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease.", "Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial.", "Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease.", "The effect of inhaled corticosteroids on bronchoalveolar lavage cells and IL-8 levels in stable COPD patients.", "Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease.", "One-year treatment with mometasone furoate in chronic obstructive pulmonary disease.", "Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group.", "Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial.", "The effect of high-dose inhaled beclomethasone dipropionate in patients with stable COPD.", "Corticosteroid trials in non-asthmatic chronic airflow obstruction: a comparison of oral prednisolone and inhaled beclomethasone dipropionate.", "Exhaled nitric oxide and hydrogen peroxide in patients with chronic obstructive pulmonary disease: effects of inhaled beclomethasone.", "Effect of salmeterol/fluticasone propionate on airway inflammation in COPD: a randomised controlled trial.", "Effects of long-term treatment with corticosteroids in COPD.", "In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation.", "The efficacy of inhaled corticosteroids in the management of non asthmatic chronic airflow obstruction.", "Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness.", "Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease: a randomized trial.", "A double-blind comparison of oral prednisolone 40 mg/day with inhaled beclomethasone dipropionate 1500 ug/day in patients with adult onset chronic obstructive airways disease.", "Predictive value and utility of oral steroid testing for treatment of COPD in primary care: the COOPT study.", "The effect of inhaled corticosteroids on the development of emphysema in smokers assessed by annual computed tomography.", "Inhaled budesonide therapy for patients with stable COPD.", "Short- and long-term efficacy of fluticasone propionate in subjects with early signs and symptoms of chronic obstructive pulmonary disease. Results of the DIMCA study.", "Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease.", "Effects of corticosteroids on bronchodilator action in chronic obstructive lung disease.", "The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD.", "A double-blind placebo-controlled study of the effect of inhaled beclomethasone dipropionate for 2 years in patients with nonasthmatic chronic obstructive pulmonary disease.", "Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.", "The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease.", "Controlled trial of inhaled fluticasone propionate in moderate to severe COPD.", "Does addition of inhaled steroid to combined bronchodilator therapy affect health status in patients with COPD?", "The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study.", "Effect of adjunct fluticasone propionate on airway physiology during rest and exercise in COPD.", "Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis.", "Aerosolized beclomethasone in chronic bronchitis. Improved pulmonary function and diminished airway inflammation.", "Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease.", "Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease.", "Steroid reversibility test followed by inhaled budesonide or placebo in outpatients with stable chronic obstructive pulmonary disease. The Danish Society of Respiratory Medicine.", "Effectiveness of fluticasone propionate and salmeterol combination delivered via the Diskus device in the treatment of chronic obstructive pulmonary disease.", "Effects of inhaled HFA beclomethasone on pulmonary function and symptoms in patients with chronic obstructive pulmonary disease." ]

[ "Inhaled corticosteroids are known to be beneficial for patients with asthma, but their role in treating patients with stable chronic obstructive pulmonary disease (COPD) remains controversial. A study was undertaken to determine whether inhaled corticosteroids are of functional benefit in patients who did not show improvement with a trial of oral corticosteroids.\n In phase I patients with stable COPD were given a two week course of oral placebo followed by two weeks of prednisone 40 mg per day in a single blind manner to distinguish between responders and non-responders to oral corticosteroids. In phase II a double blind, randomised, parallel group trial of inhaled budesonide 1600 micrograms per day versus placebo was carried out in 79 nonresponders to oral corticosteroids. The primary outcome measure was forced expiratory volume in one second (FEV1), and secondary outcome measures were exercise capacity, dyspnoea with exertion, quality of life, peak expiration flow rate, and respiratory symptoms.\n Randomisation allocated 39 subjects to inhaled corticosteroids and 40 to placebo. There was no difference in the change in FEV1 from baseline between the treatment and placebo groups; mean difference -12 ml (95% CI -88 to 63) at three months and -4 ml (95% CI -95 to 87) at six months. The proportion of patients with a 15% or greater improvement was no higher among those receiving inhaled corticosteroids than in the placebo group at any of the follow up visits. Changes in secondary outcomes were also no different.\n Inhaled corticosteroids, even at high doses, were of no physiological or functional benefit in these patients with advanced COPD.", "Small studies have suggested that inhaled corticosteroids can suppress systemic inflammation in chronic obstructive pulmonary disease (COPD).\n To determine the effect of inhaled corticosteroids with or without long-acting beta(2)-adrenergic agonist on systemic biomarkers of inflammation.\n We conducted a double-blind randomized placebo-controlled trial across 11 centers (n = 289 patients with FEV(1) of 47.8 +/- 16.2% of predicted) to compare the effects of inhaled fluticasone alone or in combination with salmeterol against placebo on circulating biomarkers of systemic inflammation over 4 weeks. The primary endpoint was C-reactive protein (CRP) level. Secondary molecules of interest were IL-6 and surfactant protein D (SP-D).\n Neither fluticasone nor the combination of fluticasone/salmeterol had a significant effect on CRP or IL-6 levels. There was, however, a significant reduction in SP-D levels with fluticasone and fluticasone/salmeterol compared with placebo (P = 0.002). Health status also improved significantly in both the fluticasone and fluticasone/salmeterol groups compared with placebo, driven mostly by improvements in the symptom scores. Changes in the circulating SP-D levels were related to changes in health status scores. FEV(1) improved significantly only in the fluticasone/salmeterol group compared with placebo.\n ICS in conjunction with long-acting beta(2)-adrenergic agonist do not reduce CRP or IL-6 levels in serum of patients with COPD over 4 weeks. They do, however, significantly reduce serum SP-D levels. These data suggest that these drugs reduce lung-specific but not generalized biomarkers of systemic inflammation in COPD.", "Systemic inflammation is present in chronic obstructive pulmonary disease (COPD), which has been linked to cardiovascular morbidity and mortality. We determined the effects of oral and inhaled corticosteroids on serum markers of inflammation in patients with stable COPD. We recruited 41 patients with mild to moderate COPD. After 4 weeks during which inhaled corticosteroids were discontinued, patients were assigned to fluticasone (500 mcg twice a day), oral prednisone (30 mg/day), or placebo over 2 weeks, followed by 8 weeks of fluticasone at 500 mcg twice a day and another 8 weeks at 1,000 mcg twice a day. Withdrawal of inhaled corticosteroids increased baseline C-reactive protein (CRP) levels by 71% (95% confidence interval [CI], 16-152%). Two weeks with inhaled fluticasone reduced CRP levels by 50% (95% CI, 9-73%); prednisone reduced it by 63% (95% CI, 29-81%). No significant changes were observed with the placebo. An additional 8 weeks of fluticasone were associated with CRP levels that were lower than those at baseline (a 29% reduction; 95% CI, 7-46%). Inhaled and oral corticosteroids are effective in reducing serum CRP levels in patients with COPD and suggest their potential use for improving cardiovascular outcomes in COPD.", "Inhaled corticosteroids are known to reduce respiratory symptoms and airway responsiveness in allergic patients with asthma. The aim of the present randomised, double blind study was to assess the effect of eight weeks' treatment with inhaled budesonide in non-allergic smokers with chronic obstructive lung disease. Twenty four subjects (23 male) entered the study. Their ages ranged from 40 to 70 (mean 57) years, with a mean of 35 (range 9-80) pack years of smoking; the mean FEV1 was 53% (range 32-74%) predicted and geometric mean PC20 (histamine concentration causing a 20% fall in FEV1) 0.96 (range 0.07-7.82) mg/ml. After a two week washout, single blind, placebo period, 12 patients were allocated to treatment with budesonide 1600 microgram/day and 12 to placebo for eight weeks. The only additional drug to be taken was ipratropium bromide \"if needed.\" Twenty one patients completed the study, 10 in the budesonide group and 11 in the placebo group. The standard deviation of the difference between duplicate measurements of PC20 histamine and citric acid cough threshold made two weeks apart was below one doubling dose step. There was a significant reduction in dyspnoea in the budesonide group, but otherwise no change in symptom scores or use of ipratropium bromide over the eight weeks of treatment within or between the two groups. No significant differences in spirometric values, peak expiratory flow, PC20 histamine, or citric acid cough threshold were found between the groups. Although differences were not significant, some of the changes showed a trend in favour of budesonide. Whether a longer observation period would show a significant influence of inhaled corticosteroids in patients with chronic obstructive lung disease remains to be determined.", "The role of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) is unclear. We investigated the effects of budesonide on airway hyperresponsiveness (AHR) to methacholine (MCh) and adenosine 5'-monophosphate (AMP), to which we hypothesized the existence of greater sensitivity. Additionally, we studied the effects of budesonide on terfenadine and ipratropium bromide and on serum levels of interleukin-8 (IL-8) and histamine. Forty-four hyperresponsive smokers with moderate to severe COPD participated in the study. MCh and AMP challenges were given on three study days, after pretreatment with single doses of ipratropium bromide, terfenadine, or placebo. Thereafter, subjects were randomized to 6 wk treatment with either 1,600 microg budesonide or placebo, and the same three study days were repeated. Budesonide, as compared with placebo, did not significantly change PC20AMP, PC20MCh, or FEV1 after placebo pretreatment. Budesonide increased PC20MCh after ipratropium bromide pretreatment, from 5.05 to 10.20 mg/ml (p = 0.036). Budesonide decreased serum IL-8 from 9.2 +/- 3.7 to 6.2 +/- 2.1 pg/ml (p < 0.001). We conclude that AMP did not elicit greater sensitivity than MCh in assessing short-term effects of budesonide on AHR in smokers with COPD. We suggest that long-term treatment with inhaled corticosteroids might be beneficial, by reducing neutrophil load in the airways and improving the action of anticholinergic drugs.", "The effects of fluticasone propionate (FP) on sputum chemotactic activity, elastase inhibitory potential, albumin concentrations, and peripheral neutrophil function were studied in a group of patients with clinically stable, smoking-related chronic bronchitis and emphysema. Seventeen patients (50 to 75 yr of age) were entered into a double-blind, placebo-controlled study of 1.5 mg inhaled FP/d for 8 wk. Following treatment with FP the chemotactic activity of the sputum sol phase was lower than the corresponding values for the placebo group (p < 0.01). Values fell from a mean of 21.75 (+/- 1.58) during the run-in period to 18.37 (+/- 1.46; p < 0.01) after 4 wk and 17.63 (+/- 1.86; p < 0.05) after 8 wk treatment returning to 22.08 (+/- 1.26) cell/field after the washout period. The neutrophil elastase inhibitory capacity of the sputum sol phase increased (p < 0.025) with treatment from a mean of 0.177 microM elastase inhibited/L (+/- 0.05) pretreatment to 0.413 microM (+/- 0.054) after 4 wk and 0.415 microM (+/- 0.054) after 8 wk returning to 0.270 microM (+/- 0.07) after the washout period. Treatment with FP did not result in a change in the peripheral neutrophil functions studied or sputum albumin and myeloperoxidase concentrations. The results suggest that FP may play a protective role in these patients through a reduction in the chemotactic activity of lung secretions and potentially a reduction in the recruitment of neutrophils to the lung, and also by directly affecting the proteinase/antiproteinase balance, in favor of antiproteinases, within lung secretions.", "Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, placebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in patients with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 microg of budesonide or placebo, inhaled from a dry-powder inhaler, for three years.\n Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the three-year period was 140 ml in the budesonide group and 180 ml in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 ml per year in the budesonide group, as compared with a decline of 81 ml per year in the placebo group (P<0.001). From nine months to the end of treatment, the FEV1 declined at similar rates in the two groups (P=0.39). Ten percent of the subjects in the budesonide group and 4 percent of those in the placebo group had skin bruising (P<0.001). Newly diagnosed hypertension, bone fractures, postcapsular cataracts, myopathy, and diabetes occurred in less than 5 percent of the subjects, and the diagnoses were equally distributed between the groups.\n In patients with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline.", "The combination of an inhaled corticosteroid (ICS) and a long-acting bronchodilator is recommended in the treatment of patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations. Budesonide/formoterol dry powder inhaler (DPI) has demonstrated efficacy and tolerability in patients with COPD.\n To evaluate the efficacy and tolerability of budesonide/formoterol administered via one hydrofluoroalkane pressurized metered-dose inhaler (pMDI) in patients with COPD.\n This was a 6-month, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicentre study (NCT00206154) of 1704 patients aged > or =40 years with moderate to very severe COPD conducted in 194 centres in the US, Czech Republic, the Netherlands, Poland and South Africa. After 2 weeks of treatment based on previous therapy (ICSs and short-acting bronchodilators allowed during the run-in period), patients received one of the following treatments administered twice daily: budesonide/formoterol pMDI 160/4.5 microg x two inhalations (320/9 microg); budesonide/formoterol pMDI 80/4.5 microg x two inhalations (160/9 microg); budesonide pMDI 160 microg x two inhalations (320 microg) plus formoterol DPI 4.5 microg x two inhalations (9 microg); budesonide pMDI 160 microg x two inhalations (320 microg); formoterol DPI 4.5 microg x two inhalations (9 microg); or placebo.\n The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV(1)) and 1-hour post-dose FEV(1).\n Budesonide/formoterol 320/9 microg demonstrated significantly greater improvements in pre-dose FEV(1) versus formoterol (p = 0.026; pre-specified primary comparator) and 1-hour post-dose FEV(1) versus budesonide (p < 0.001; pre-specified primary comparator); budesonide/formoterol 160/9 microg demonstrated significantly greater improvements versus budesonide (p < 0.001) for 1-hour post-dose FEV(1) but not versus formoterol for pre-dose FEV(1). Dyspnoea (measured using the Breathlessness Diary) and health-related quality-of-life (HR-QOL) scores (based on the St George's Respiratory Questionnaire total score) were significantly improved with both dosage strengths of budesonide/formoterol compared with budesonide, formoterol and placebo (p < or = 0.044 for all). Although not powered a priori for comparisons, the number of exacerbations per patient-treatment year requiring treatment with oral corticosteroids and/or hospitalization was numerically (20-25%) lower with the budesonide-containing treatments (0.710-0.884) versus formoterol (1.098) and placebo (1.110). This result was driven by the exacerbations requiring treatment with oral corticosteroids (79-120 events). The number of exacerbations resulting in hospitalization was very low across treatment groups (11-22); the number per patient-treatment year was significantly different for budesonide/formoterol 320/9 microg (0.158) versus other treatment groups (0.081-0.108) except budesonide/formoterol 160/9 microg (0.139), and for budesonide/formoterol 160/9 microg versus formoterol (0.081) [p < or = 0.05]. All treatments were generally well tolerated. The incidence of individual non-fatal serious adverse events was similar across all treatment groups, except COPD, which was highest in the budesonide/formoterol 320/9 microg group (6.1%) and lowest in the budesonide (3.6%) and formoterol (3.9%) groups, with a range of 4.3-4.6% in the budesonide/formoterol 160/9 microg, budesonide plus formoterol and placebo groups. Budesonide/formoterol had a safety profile comparable with that of the monocomponents and placebo. There was no increase in the incidence of pneumonia in the active treatment groups relative to placebo.\n Budesonide/formoterol pMDI 320/9 microg demonstrated significantly greater efficacy for pulmonary function on both co-primary endpoints versus the pre-specified comparators (formoterol DPI 9 microg for pre-dose FEV(1) and budesonide pMDI 320 microg for 1-hour post-dose FEV(1)). Budesonide/formoterol pMDI 160/9 microg demonstrated significantly greater efficacy for 1-hour post-dose FEV(1) versus budesonide pMDI 320 microg. Dyspnoea scores and HR-QOL were significantly improved with both budesonide/formoterol pMDI dosage strengths versus both monocomponents and placebo. Both budesonide/formoterol pMDI dosage strengths were well tolerated relative to the monocomponents and placebo.", "The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/formoterol (Symbicort) 160/4.5 microg (delivered dose), budesonide 200 microg (metered dose), formoterol 4.5 microg or placebo. Severe exacerbations and FEV1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever beta2-agonist and safety variables were recorded. Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever beta2-agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated. These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease.", "Inhaled long-acting beta2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone.\n 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 microg salmeterol twice daily (n=372), 500 microg fluticasone twice daily (n=374), 50 microg salmeterol and 500 microg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6h and from study medication for at least 12h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol.\n All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95% CI 105-161, p<0.0001), salmeterol (73 mL, 46-101, p<0.0001), or fluticasone alone (95 mL, 67-122, p<0.0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration.\n Because inhaled long-acting beta2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD.", "Lung function in chronic obstructive pulmonary disease (COPD) can be improved acutely by oral corticosteroids and bronchodilators. Whether clinical improvement can be maintained by subsequent inhaled therapy is unknown. COPD patients (n=1,022, mean prebronchodilator forced expiratory volume in one second (FEV1) 36% predicted) initially received formoterol (9 microg b.i.d.) and oral prednisolone (30 mg o.d.) for 2 weeks. After this time, patients were randomised to b.i.d. inhaled budesonide/formoterol 320/9 microg, budesonide 400 microg, formoterol 9 microg or placebo for 12 months. Postmedication FEV1 improved by 0.21 L and health-related quality of life using the St George's Respiratory Questionnaire (SGRQ) by 4.5 units after run-in. Fewer patients receiving budesonide/formoterol withdrew from the study than those receiving budesonide, formoterol or placebo. Budesonide/formoterol patients had a prolonged time to first exacerbation (254 versus 96 days) and maintained higher FEV1 (99% versus 87% of baseline), both primary variables versus placebo. They had fewer exacerbations (1.38 versus 1.80 exacerbations per patient per year), had higher prebronchodilator peak expiratory flow, and showed clinically relevant improvements in SGRQ versus placebo (-7.5 units). Budesonide/formoterol was more effective than either monocomponent in both primary variables. Budesonide/formoterol in a single inhaler (Symbicort) maintains the benefit of treatment optimisation, stabilising lung function and delaying exacerbations more effectively than either component drug alone or placebo.", "Chronic obstructive pulmonary disease (COPD) is characterised by a chronic inflammatory process in the large and small airways, as well as in the lung parenchyma. Although the role of oral corticosteroids in the management of acute exacerbations of COPD is well documented, its role in stable COPD is not clear. We examined the anti-inflammatory effect of inhaled budesonide on the percentage of neutrophils and on interleukin-8 (IL-8) levels in bronchoalveolar lavage (BAL) and their correlation with spirometry and symptom scores. Twenty-six patients with stable COPD were randomised, in a double-blinded, placebo-controlled trial with either 800 microg of inhaled budesonide or placebo for a 6-month period. The budesonide-treated subjects had significant reductions in IL-8 levels in the BAL after therapy (mean+/-sem, 1.53+/-0.72 at baseline vs. 0.70+/-0.48 ng/ml at 6 months, P=0.004) and a reduction in the mean percentages of neutrophils (17.16+/-2.67% vs. 13.25+/-2.28% P=0.002). The improvement in sputum production was of borderline (P=0.058) significance but there was no improvement in lung function. In stable patients with COPD, treatment with inhaled budesonide for a period of 6 months has a positive effect on markers of lung inflammation, as assessed by reduction in percentage neutrophils and IL-8 concentration in BAL.", "Long-acting beta-agonists and inhaled corticosteroids are used to treat chronic obstructive pulmonary disease (COPD), but their effect on survival is unknown.\n We conducted a randomized, double-blind trial comparing salmeterol at a dose of 50 microg plus fluticasone propionate at a dose of 500 microg twice daily (combination regimen), administered with a single inhaler, with placebo, salmeterol alone, or fluticasone propionate alone for a period of 3 years. The primary outcome was death from any cause for the comparison between the combination regimen and placebo; the frequency of exacerbations, health status, and spirometric values were also assessed.\n Of 6112 patients in the efficacy population, 875 died within 3 years after the start of the study treatment. All-cause mortality rates were 12.6% in the combination-therapy group, 15.2% in the placebo group, 13.5% in the salmeterol group, and 16.0% in the fluticasone group. The hazard ratio for death in the combination-therapy group, as compared with the placebo group, was 0.825 (95% confidence interval [CI], 0.681 to 1.002; P=0.052, adjusted for the interim analyses), corresponding to a difference of 2.6 percentage points or a reduction in the risk of death of 17.5%. The mortality rate for salmeterol alone or fluticasone propionate alone did not differ significantly from that for placebo. As compared with placebo, the combination regimen reduced the annual rate of exacerbations from 1.13 to 0.85 and improved health status and spirometric values (P<0.001 for all comparisons with placebo). There was no difference in the incidence of ocular or bone side effects. The probability of having pneumonia reported as an adverse event was higher among patients receiving medications containing fluticasone propionate (19.6% in the combination-therapy group and 18.3% in the fluticasone group) than in the placebo group (12.3%, P<0.001 for comparisons between these treatments and placebo).\n The reduction in death from all causes among patients with COPD in the combination-therapy group did not reach the predetermined level of statistical significance. There were significant benefits in all other outcomes among these patients. (ClinicalTrials.gov number, NCT00268216 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.", "Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS). This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing.In a 52-week, randomized, double-blind, placebo-controlled study, 911 subjects with moderate-to-severe COPD managed without ICS received MF-DPI 800 microg QD PM, MF-DPI 400 microg BID, or placebo. The change from baseline in postbronchodilator forced expiratory volume in 1 second (FEV1), total COPD symptom scores, and health status as well as the percentage of subjects with a COPD exacerbation were assessed. Adverse events were recorded. Mometasone furoate administered via a dry powder inhaler 800 microg QD PM and 400 microg BID significantly increased postbronchodilator FEV1 from baseline (50 mL and 53 mL, respectively, versus a 19 mL decrease for placebo; P < 0.001). The percentage of subjects exacerbating was significantly lower in the pooled MF-DPI groups than in the placebo group (P = 0.043). Subjects receiving MF-DPI 400 microg BID reported a statistically significant (19%) reduction in COPD symptom scores compared with placebo (P < 0.001). Health status as measured with St. George's Respiratory Questionnaire (SGRQ) improved significantly in all domains (Total, Activity, Impacts, and Symptoms) in the pooled MF-DPI groups versus placebo (P < or = 0.031). MF-DPI treatment was well tolerated.Once-daily MF-DPI improved lung function and health status in subjects with moderate-to-severe COPD and was comparable to BID MF-DPI.", "The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) remains controversial because of a lack of placebo-controlled studies. We compared the effect of inhaled fluticasone propionate with placebo in the treatment of patients with COPD.\n We used a randomised, double-blind, placebo-controlled design. We enrolled from 13 European countries, New Zealand, and South Africa, 281 outpatient current or ex-smokers, aged between 50 and 75 years. They had a forced expiratory volume in 1 s (FEV1) of between 35% and 90% of predicted normal values, a ratio of FEV1 to forced vital capacity of 70% or less and bronchodilator reversibility of less than 15%, as well as a history of chronic bronchitis. Patients were randomly assigned fluticasone propionate 500 microg (n=142) or placebo (n=139) twice daily via a metered-dose inhaler for 6 months. The main outcome measures were the number of patients who had at least one exacerbation by the end of treatment, the number and severity of exacerbations, clinic lung function, diary card symptoms and peak expiratory flow and 6 min walking distance.\n 51 (37%) patients in the placebo group compared with 45 (32%) in the fluticasone propionate group had had at least one exacerbation by the end of treatment (p=0.449). Significantly more patients had moderate or severe exacerbations in the placebo group than in the fluticasone propionate group (86% vs 60%, p<0.001). Diary-card and clinic morning peak expiratory flows improved significantly in the fluticasone propionate group (p<0.001, p=0.048, respectively), as did clinic FEV1 (p<0.001), forced vital capacity (p<0.001), and mid-expiratory flow (p=0.01). Symptom scores for median daily cough and sputum volume were significantly lower with fluticasone propionate treatment than with placebo (p=0.004 and p=0.016, respectively). At the end of treatment, patients on fluticasone propionate had increased their 6 min walking distance significantly more than those on placebo (p=0.032). Fluticasone propionate was tolerated as well as placebo, with few adverse effects and without a clinically important effect on mean serum cortisol concentration.\n Fluticasone propionate may be of clinical benefit in patients with COPD over at least 6 months. Inhaled corticosteroids may have an important role in the long-term treatment of COPD.", "Little is known about the long-term efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD). We investigated the efficacy of inhaled budesonide on decline in lung function and respiratory symptoms in a 3-year placebo-controlled study of patients with COPD.\n We used a parallel-group, randomised, double-blind, placebo-controlled design in a singlecentre study, nested in a continuing epidemiological survey (the Copenhagen City Heart Study). Inclusion criteria were as follows: no asthma; a ratio of forced expiratory volume in 1 s (FEV1) and vital capacity of 0.7 or less; FEV1 which showed no response (<15% change) to 1 mg inhaled terbutaline or prednisolone 37.5 mg orally once daily for 10 days. 290 patients were randomly assigned budesonide, 800 microg plus 400 microg daily for 6 months followed by 400 microg twice daily for 30 months, or placebo for 36 months. The mean age of the participants was 59 years and the mean FEV1 2.37 L or 86% of predicted. The main outcome measure was rate of FEV1 decline. Analyses were by intention to treat.\n The crude rates of FEV1 decline were slightly smaller than expected (placebo group 41.8 mL per year, budesonide group 45.1 mL per year). The estimated rates of decline from the regression model did not differ significantly (49.1 mL vs 46.0 mL per year; difference 3.1 mL per year [95% CI -12.8 to 19.0]; p=0.7). Before the study, the minimum relevant difference was defined as 20 mL per year; this difference was outside the 95% CI. No effect of inhaled budesonide was seen on respiratory symptoms. 316 exacerbations occurred during the study period, 155 in the budesonide group and 161 in the placebo group. Treatment was well tolerated.\n Inhaled budesonide was of no clinical benefit in COPD patients recruited from the general population by screening. We question the role of long-term inhaled corticosteroids in the treatment of mild to moderate COPD.", "The benefits of inhaled corticosteroids in the management of COPD are less apparent than they are in asthma therapy, and the potential for adverse systemic effects of high-dose inhaled corticosteroids has been recognized recently. It is therefore essential to know the maximal obtainable benefits in order to assess the risk/benefit ratio of this treatment.\n The aim of this study was to investigate the maximal obtainable benefits of high-dose inhaled corticosteroids, 3 mg/d of beclomethasone dipropionate (BDP), when used in combination with adequate doses of regular bronchodilators in patients with stable COPD.\n Thirty patients with stable COPD completed a randomized, double-blind, placebo-controlled cross-over trial with either 3 mg/d of BDP or with a matching placebo using a metered-dose inhaler with a spacer device for 4 weeks during each treatment period. All of the patients continued to inhale both 400 microg of salbutamol qid and 80 microg of ipratropium bromide qid.\n The mean prebronchodilator FEV1 was 0.97+/-0.35 L during the placebo period and 1.08+/-0.38 L during the BDP period (p < 0.001). While on BDP, five patients demonstrated a response in their FEV1 of more than 8.5% of the predicted value, which was above the range that covered 95% of the distribution of the placebo response. The mean absolute improvement in the FEV1 in these 5 objective responders was 0.34+/-0.10 L, compared to 0.06+/-0.09 L in the 25 objective nonresponders. Symptom scores for wheezing and dyspnea were significantly better with BDP than with placebo. Hoarseness and sore throat were associated more with BDP treatment.\n Although a considerable minority of patients benefited substantially from this treatment, the overall outcome does not seem to justify the widespread use of this treatment in the light of increasing recognition of the potential adverse systemic effects of high-dose inhaled corticosteroids.", "One hundred and twenty seven adults considered on clinical grounds to have non-asthmatic chronic airflow obstruction entered a randomised, double blind, placebo controlled, crossover trial comparing the physiological response to inhaled beclomethasone dipropionate 500 micrograms thrice daily with oral prednisolone 40 mg a day, both given for two weeks. One hundred and seven patients completed the study. Response was assessed as change in FEV1 and FVC measured on the last treatment day, and as change in mean peak expiratory flow (PEF) over the final seven days of treatment from home PEF recordings performed five times daily. A full response to treatment was defined as an increase in FEV or FVC, or an increase in mean daily PEF over the final seven days of treatment, of at least 20% from baseline values. An improvement in one measurement of at least 15%, or of 10% in any two measurements, was defined as a partial treatment response. Response to placebo showed a significant order effect, suggesting a carry over effect of active treatment of at least three weeks. Response to active treatment was therefore related to initial baseline values, and compared with placebo by considering responses in the first treatment phase only. A full response to oral prednisolone (16/38) was significantly more common than to placebo (3/35). The number of full responses to inhaled beclomethasone (8/34) did not differ significantly from the number responding to oral prednisolone or placebo in the first treatment phase, though full and partial responses to inhaled beclomethasone (12/34) were significantly more common than those to placebo (4/35). When all three treatment phases were considered 44/107 patients showed a full response to one or both forms of corticosteroid treatment, a response to prednisolone (39) occurring more frequently than to inhaled beclomethasone (26). Only 21 of the 44 responders showed a response to both forms of treatment. Inhaled beclomethasone dipropionate 500 micrograms thrice daily was inferior to oral prednisolone 40 mg per day, but better than placebo, in producing improvement in physiological measurements in patients thought to have nonasthmatic chronic airflow obstruction. It was, however, an effective alternative in over half of those showing a response to prednisolone.", "There is controversy about the role of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD). Although they appear to have little impact on airways obstruction or its progression, their use may reduce the frequency and/or severity of exacerbations in a subset of patients. We undertook the following study to determine the impact of inhaled corticosteroid on two noninvasive markers of airways inflammation. We assigned 20 stable nonsmoking patients with COPD in random, double-blind crossover fashion to two 2-wk treatment periods with inhaled beclomethasone 500 microg twice daily or matching placebo, followed by a 2-wk washout period. We measured exhaled nitric oxide (ENO), breath condensate H(2)O(2), and flow volume spirometry at weekly intervals. Median baseline ENO was 26.2 (19.3 to 54.8) ppb and fell significantly following 1 and 2 wk of beclomethasone (-10.6 ppb, p = 0.002, and -6.3 ppb, p = 0.013, respectively) but was unchanged by placebo inhalation. Breath condensate H(2)O(2) levels did not change significantly with inhaled beclomethasone or placebo. Although there were no significant changes in FEV(1) with BDP therapy, there was a moderate inverse correlation between changes in ENO and changes in FEV(1) (r -0.50). We conclude that inhaled beclomethasone reduces ENO levels in stable nonsmoking patients with COPD, a finding compatible with an antiinflammatory mechanism of action.", "Airway inflammation in chronic obstructive pulmonary disease (COPD) is characterised by infiltration of CD8+ T cells and CD68+ macrophages and an increased number of neutrophils, whereas few studies have described the presence of eosinophils. Although the anti-inflammatory effects of corticosteroids in stable COPD are unclear, recent studies suggest that combination therapy could be beneficial. A study was therefore undertaken to evaluate combined salmeterol/fluticasone propionate (SFC) and fluticasone propionate (FP) alone on inflammatory cells in the airways of patients with COPD.\n Patients were treated in a randomised, double blind, parallel group, placebo-controlled trial with either a combination of 50 microg salmeterol and 500 microg FP twice daily (SFC, n = 19, 19 men, mean age 62 years), 500 microg FP twice daily (n = 20, 15 men, mean age 64 years) or placebo (n = 21, 17 men, mean age 66 years) for 3 months. At the start and end of treatment bronchoscopy with bronchial biopsies was performed and the numbers of CD8+ T lymphocytes, CD68+ macrophages, neutrophils and eosinophils were measured.\n CD8+ cells were significantly reduced by SFC compared with placebo (difference -98.05 cells/mm(2); 95% CI -143.14 to -52.9; p<0.001). Such a marked effect was not seen with FP alone (-44.67 cells/mm(2); 95% CI -90.92 to 1.57; p = 0.06). CD68+ macrophages were also reduced by SFC compared with placebo (difference -31.68 cells/mm(2); 95% CI -61.07 to -2.29; p = 0.03) but not by FP. SFC did not significantly change neutrophils and eosinophils compared with placebo.\n SFC has airway anti-inflammatory effects not seen with inhaled corticosteroids alone.", "To determine the effectiveness of treatment with corticosteroids in patients with COPD.\n In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects were treated in a double-blind, randomized, placebo-controlled, parallel way with inhaled budesonide (bud), 1,600 micrograms/d; inhaled budesonide, 1,600 micrograms/d, plus oral prednisolone, 5 micrograms/d (bud + pred); or placebo (plac). Clinical assessment (history, physical examination, and spirometry) was carried out every 2 months. The rate of decline in FEV1 was assessed by calculating individual regression co-efficients from linear regression of FEV1 on time for each subject.\n Eleven patients dropped out. The number of withdrawals due to pulmonary problems was significantly higher in the plac group (n = 5 out of 18) than in the actively treated groups (n = 2 out of 40). Treatment with corticosteroids significantly reduced pulmonary symptoms. Median decline of FEV1 was 60 mL/yr in the plac group, 40 mL/yr in the bud + pred group, and 30 mL/yr in the bud group. Variation was large and differences were not statistically significant. No treatment effect was found on frequency or duration of exacerbations, possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group. Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone. Morning plasma cortisol levels remained within the normal range in all three groups.\n Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems. Lung function decline tends to decrease during treatment with inhaled corticosteroids. The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD.", "Systemic corticosteroids have been recommended as a therapeutic option in patients with moderate to severe COPD. In an early stage of the disease, i.e. chronic bronchitis with mild or no airflow obstruction, a trial with inhaled steroids could reveal potential benefits, particularly in terms of a modulation of airway inflammation. We therefore investigated the effect of inhaled fluticasone (1000 microg day(-1)) on markers of airway inflammation in 19 patients with chronic bronchitis (mean+/-SEM FEV1, 83.4+/-3.0% predicted; FEV1/VC, 67.5+/-2.4%) in a double-blind, cross-over, placebo-controlled manner. Visits were performed before and after two 4-week treatment periods. separated by a 4-week washout period. Lung function, the concentration of exhaled nitric oxide, differential cell counts in induced sputum and the number of cells positive for iNOS, as well as the levels of LDH, ECP, neutrophil elastase and IL-8 in sputum supernatants were determined. Although the total cell number decreased significantly after fluticasone (geometric mean 12.3 vs. 7.7 x 10(6)/ml; P<0.05) it was not significantly different from the change observed after placebo (14.2 vs. 10.6 x 10(6)/ml; n.s.). None of the other parameters showed statistically significant changes after fluticasone or placebo and the results did not depend on the presence of airway hyperresponsiveness. We conclude that in patients with chronic bronchitis short-term treatment with inhaled corticosterids did not improve lung function or inflammatory parameters to an extent which was statistically significant as compared to spontaneous variability.", "The aims of this investigation were to evaluate the efficacy of regular inhaled beclomethasone in the control of symptoms and lung function with non-asthmatic smoking related obstructive pulmonary disease and to evaluate the relationship between clinical responses to a short course of oral prednisone and longer term outcomes using inhaled steroid.\n The study was a randomised, double blind, placebo controlled, crossover investigation in 18 patients. The active treatment was inhaled beclomethasone 1000 micrograms given twice daily for three months by metered dose inhaler. At the end of each treatment period, patients received oral prednisone 30 mg/day for ten days. The two treatment phases were separated by a one month washout interval. Peak flow rates, symptom scores and \"rescue\" bronchodilator use were recorded twice daily. Lung function (FEV1, FVC and lung volumes) and bronchial hyperresponsiveness (PC20 methacholine) were measured at monthly visits. The number of exacerbations requiring intervention therapy were also recorded.\n There were no consistent benefits attributable to beclomethasone. Lung function was not significantly better as a result of active treatment. Sputum production improved but other symptom scores were similar during active and placebo therapy. Three patients exhibited an increase in FEV1 of 15% or more during active treatment but did not do so when oral prednisone was administered immediately after the period of placebo treatment. A further three patients showed an improvement in FEV1 of 15% or more with oral prednisone but failed to improve during treatment with inhaled beclomethasone. The predictive value of the \"trial of steroid\" was 0% and 81.3% for positive and negative outcomes respectively.\n Our results indicate that in non-asthmatic chronic obstructive pulmonary disease inhaled corticosteroid fails to achieve significant improvements in either lung function or symptoms. The response to a \"trial of steroid\" using oral prednisone is not clinically helpful in selecting the small number of patients who may subsequently benefit from this form of therapy.", "Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids does not appear to be as effective as similar treatment of asthma. It seems that only certain subgroups of patients with COPD benefit from steroid treatment. A study was undertaken to examine whether inhaled fluticasone propionate (FP) had an effect on lung function and on indices of inflammation in a subgroup of COPD patients with bronchial hyperresponsiveness (BHR).\n Twenty three patients with COPD were studied. Patients had to be persistent current smokers between 40 and 70 years of age. Non-specific BHR was defined as a PC(20) for histamine of <or=8 mg/ml. Patients received either 2 x 500 microg FP or placebo for 6 months. Expiratory volumes were measured at monthly visits, BHR was determined at the start of the study and after 3 and 6 months, and bronchial biopsy specimens were taken at the start and after 6 months of treatment. Biopsy specimens from asymptomatic smokers served as controls.\n In contrast to asthma, indices of BHR were not significantly influenced by treatment with FP. Forced expiratory volume in 1 second (FEV(1)) showed a steep decline in the placebo group but remained stable in patients treated with FP. FEV(1)/FVC, and maximal expiratory flows at 50% and 25% FVC (MEF(50), MEF(25)) were significantly increased in the FP treated patients compared with the placebo group. Biopsy specimens were analysed for the presence of CD3+, CD4+, CD8+, MBP+, CD15+, CD68+, CD1a, and tryptase cells. FP treatment resulted in marginal reductions in these indices of inflammation.\n In patients with COPD and BHR, FP has a positive effect on indices of lung function compared with placebo. Bronchial inflammation analysed in bronchial biopsy specimens is only marginally reduced.", "Inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists (LABAs) are used to treat moderate to severe chronic obstructive pulmonary disease (COPD).\n To determine whether long-term ICS therapy, with and without LABAs, reduces inflammation and improves pulmonary function in COPD.\n Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00158847)\n 2 university medical centers in The Netherlands.\n 114 steroid-naive current or former smokers with moderate to severe COPD.\n Cell counts in bronchial biopsies and sputum (primary outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical outcomes every 3 months.\n Random assignment by minimization method to receive fluticasone propionate, 500 microg twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 microg twice daily, and salmeterol, 50 microg twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29).\n 101 patients were greater than 70% adherent to therapy. Fluticasone therapy decreased counts of mucosal CD3(+) cells (-55% [95% CI, -74% to -22%]; P = 0.004), CD4(+) cells (-78% [CI, -88% to 60%]; P < 0.001), CD8(+) cells (-57% [CI, -77% to -18%]; P = 0.010), and mast cells (-38% [CI, -60% to -2%]; P = 0.039) and reduced hyperresponsiveness (P = 0.036) versus placebo at 6 months, with effects maintained after 30 months. Fluticasone therapy for 30 months reduced mast cell count and increased eosinophil count and percentage of intact epithelium, with accompanying reductions in sputum neutrophil, macrophage, and lymphocyte counts and improvements in FEV(1) decline, dyspnea, and quality of life. Reductions in inflammatory cells correlated with clinical improvements. Discontinuing fluticasone therapy at 6 months increased counts of CD3(+) cells (120% [CI, 24% to 289%]; P = 0.007), mast cells (218% [CI, 99% to 407%]; P < 0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical outcome. Adding salmeterol improved FEV(1) level.\n The study was not designed to evaluate clinical outcomes. Measurement of primary outcome was not available for 24% of patients at 30 months.\n ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD. Adding LABAs does not enhance these effects. .", "A double-blind cross-over trial was carried out on 83 sequential out-patients presenting with adult onset chronic airflow obstruction who were not clearly asthmatic. The study consisted of three treatment phases each lasting two weeks with a two week interval between each phase. The treatment phases were prednisolone 40 mg daily, beclomethasone dipropionate 500 ug three times a day and placebo, administered in a random order. FEV1 and FVC were measured at the end of each of the treatment phases and peak expiratory flow rate five times a day throughout. Over the study period 25 (30%) patients responded with an improvement of greater than or equal to 20% in at least one of the parameters measured as compared with the best of either baseline or placebo measurements. A further eight patients were classified as partial responders with an improvement of greater than 15% in any single parameter or greater than 10% in any two parameters. A similar number responded to beclomethasone [15] as responded to prednisolone [16]. Only six patients, however, responded fully to both forms of steroid therapy. A number of patients responded to one form of steroid treatment only which was also comparable between the two groups (prednisolone 10, beclomethasone 9). For full and partial responders mean improvement in FEV1, FVC and PEFR was greater during the prednisolone phase than during the beclomethasone phase, however, the difference did not achieve statistical significance.", "The oral prednisolone test is widely used to distinguish chronic obstructive pulmonary disease (COPD) patients who might benefit from inhaled steroid treatment. Previous studies used selected patient groups that did not represent the large COPD population in primary care.\n The study included smokers and exsmokers with chronic bronchitis or COPD from primary care, who underwent prednisolone testing (30 mg for 14 days) before randomization in a three-year follow-up randomized controlled trial (COOPT Study). Spirometry was performed before and after the test. Responders and nonresponders were classified according to international criteria. Effectiveness of inhaled fluticasone relative to placebo was compared in terms of health status (Chronic Respiratory Disease Questionnaire), exacerbations, and postbronchodilator forced expiratory volume in one second (FEV(1)), using repeated measurement analysis.\n Two hundred eighty-six patients recruited from 44 primary care practices were randomized. Nine percent to 16% of the COPD population was classified as responder, depending on the international guideline criteria used. On average, responders did not reach the minimum clinically important difference in health status (0.29 points/year, P = 0.05), although a borderline significant effect of inhaled fluticasone was noted. Possible clinically relevant reductions in exacerbation rate (rate ratio 0.67) and FEV(1) decline (39 mL/year) occurred in responders, but did not reach statistical significance.\n Oral steroid testing identifies a limited proportion of COPD patients, but does not reveal any clinically relevant benefit from inhaled steroid treatment on health status. No significant effects on exacerbation rate and lung function decline occurred.", "The objective was to evaluate the effect of inhaled corticosteroids on disease progression in smokers with moderate to severe chronic obstructive pulmonary disease (COPD), as assessed by annual computed tomography (CT) using lung density (LD) measurements. Two hundred and fifty-four current smokers with COPD were randomised to treatment with either an inhaled corticosteroids (ICS), budesonide 400 microg bid, or placebo. COPD was defined as FEV(1) < or = 70% pred, FEV(1)/FVC < or = 60% and no reversibility to beta(2)-agonists and oral corticosteroids. The patients were followed for 2-4 years with biannual spirometry and annual CT and comprehensive lung function tests (LFT). CT images were analysed using Pulmo-CMS software. LD was derived from a pixel-density histogram of the whole lung as the 15th percentile density (PD15) and the relative area of emphysema at a threshold of -910 Hounsfield units (RA-910), and both were volume-adjusted to predicted total lung capacity. At baseline, mean age was 64 years and 64 years; mean number of pack-years was 56 and 56; mean FEV(1) was 1.53 L (51% pred) and 1.53 L (53% pred); mean PD15 was 103 g/L and 104 g/L; and mean RA-910 was 14% and 13%, respectively, for the budesonide and placebo groups. The annual fall in PD15 was -1.12 g/L in the budesonide group and -1.81 g/L in the placebo group (p = 0.09); the annual increase in RA-910 was 0.4% in the budesonide group and 1.1% in the placebo group (p = 0.02). There was no difference in annual decline in FEV(1) between ICS (-54 mL) and placebo (-56 mL) (p = 0.89). Long-term budesonide inhalation shows a non-significant trend towards reducing the progression of emphysema as determined by the CT-derived 15th percentile lung density from annual CT scans in current smokers with moderate to severe COPD.", "A significant minority of patients with COPD have favorable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side effects. Long-term administration of inhaled steroids is a safe means of treatment. We hypothesized that treatment with high-dose inhaled budesonide would improve clinical symptoms and pulmonary function in subjects with COPD, and that the response to inhaled beta 2-agonist will serve to individualize steroid responders. We compared a 6-week course of 800 micrograms/d inhaled budesonide with placebo, separated by 4 weeks when no medication was taken, in a double-blind crossover trial, in 8 patients responding to inhaled beta 2-agonist, and in 22 nonresponders with stable COPD. In six of eight \"responders to beta 2-agonist,\" there was a significant improvement in the FEV1 (defined as > or = 20%) following inhaled budesonide, as compared with placebo. In the 22 \"nonresponders to beta 2-agonist,\" there was no significant improvement in the mean FEV1 (1.41 +/- 0.1 L before, and 1.61 +/- 0.1 L after treatment) with inhaled budesonide or placebo. Over the 6-week course of treatment by either budesonide or placebo, the nonresponders reported similar beta 2-agonist consumption (4.8 +/- 0.2 and 5.0 +/- 0.1 puffs per patient per day, respectively). However, there was a significant difference between the two periods of treatment in the responders as for the mean daily number of beta 2-agonist inhalations (2.4 +/- 0.1 in the budesonide period as compared with 5.3 +/- 0.1 in the placebo period; p < 0.005). We conclude that treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about 25% of patients with stable COPD, and this rate is increased to about 75% in patients who respond to beta 2-agonist inhalation.", "Early treatment with inhaled corticosteroids may prevent progression of irreversible obstruction in COPD, especially in patients with bronchial hyperresponsiveness. We investigated the clinical effects of early introduction of inhaled steroids in subjects showing early signs and symptoms of COPD without a prior clinical diagnosis.\n Study subjects were detected in a general population screening and monitoring program. Those with a moderately accelerated annual FEV1 decline and persistent respiratory symptoms were invited to participate in a 2-year randomized controlled trial comparing fluticasone propionate DPI 250 microg b.i.d. with placebo. Pre- and post-bronchodilator (BD) FEV1, PC20 histamine, functional status (COOP/WONCA charts) and occurrence of exacerbations were periodically assessed. Subjects recorded respiratory symptoms. Post-BD FEV1 decline served as the main outcome. Multivariable repeated measurements analysis techniques were applied.\n 48 subjects were randomized (24 fluticasone, 24 placebo). After 3 months, the post-BD FEV1 had increased with 125 ml (SE = 68, P = 0.075) and the pre-BD FEV1 with 174 ml (SE 90, P = 0.059) in the fluticasone relative to the placebo group. The subsequent post-BD and pre-BD FEV1 decline were not beneficially modified by fluticasone treatment. There were no statistically significant differences in respiratory symptoms, functional status, or exacerbations favoring fluticasone. Subgroup analysis indicated that the presence of bronchial hyperresponsiveness modified the initial FEV1 response on fluticasone, but not the subsequent annual FEV1 decline.\n Early initiation of inhaled steroid treatment does not seem to affect the progressive deterioration of lung function or other respiratory health outcomes in subjects with early signs and symptoms of COPD. In subjects at risk for, or in an early stage of COPD, long-term inhaled steroid treatment should not be based on a single spirometric evaluation after 3 months.", "Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease (COPD), despite lack of proven efficacy. Because COPD involves airway inflammation and probable protease-antiprotease imbalance, we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms. Thirteen patients with COPD were treated with fluticasone propionate (500 microg twice a day) for 4 wk, delivered via MDI and spacer, in a double-blind crossover study. There was no clinical benefit in terms of lung function or symptom scores, and induced sputum inflammatory cells, percentage neutrophils, and IL-8 levels were unchanged. Sputum supernatant elastase activity, matrix metalloproteinase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibitor (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment. These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD. Furthermore, inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction.", "Short term treatment with corticosteroids does not usually reduce airflow limitation and airway responsiveness in patients with chronic obstructive lung disease. We investigated whether corticosteroids modulate the effects of inhaled salbutamol and ipratropium bromide.\n Ten non-allergic subjects with stable disease were investigated; eight completed the randomised, double blind, three period cross over study. Treatment regimens consisted of 1.6 mg inhaled budesonide a day for three weeks, 40 mg oral prednisone a day for eight days, and placebo. After each period cumulative doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo were administered on separate days until a plateau in FEV1 was reached. A histamine challenge was then performed.\n At the end of placebo treatment mean FEV1 was 55.5% predicted after inhaled placebo, 67.9% predicted after salbutamol and 64.0% predicted after ipratropium. Compared with the results after the placebo period the FEV1 with salbutamol increased by 0.7% predicted after treatment with budesonide and by 0.7% predicted after treatment with prednisone; the FEV1 with ipratropium increased by 0.7% predicted after budesonide and by 4.8% predicted after prednisone; none of these changes was significant. After placebo treatment the geometric mean PC20 was 0.55 mg/ml after placebo, 1.71 mg/ml after salbutamol and 0.97 mg/ml after ipratropium. Compared with the placebo period the PC20 with salbutamol was increased by 0.86 doubling concentrations after treatment with budesonide, and by 0.67 doubling concentrations after prednisone; the PC20 with ipratropium increased by 0.03 and 0.34 doubling concentrations after budesonide and after prednisone respectively compared with placebo; none of these changes was significant.\n In non-allergic subjects with chronic obstructive lung disease short term treatment with high doses of inhaled or oral corticosteroids does not modify the bronchodilator response to salbutamol or ipratropium or the protection provided by either drug against histamine. Salbutamol produces greater protection from histamine induced bronchoconstriction than ipratropium.", "To compare the efficacy and safety of the inhaled corticosteroid fluticasone propionate (FP) and the inhaled long-acting beta(2)-agonist salmeterol (SM), when administered together in a single device (Diskus; GlaxoSmithKline, Inc; Research Triangle Park, NC), with that of placebo and the individual agents alone in patients with COPD.\n Randomized, double-blind, multicenter, placebo-controlled study.\n Seventy-six investigative sites in the United States.\n Seven hundred twenty-three patients > or =40 years of age with COPD and a mean baseline FEV(1) of 42% predicted.\n FP (250 microg), SM (50 microg), FP plus SM combined in a single inhaler (FSC), or placebo administered twice daily through the Diskus device for 24 weeks.\n Primary efficacy measures were morning predose (ie, trough FEV(1)) for FSC compared with SM and 2-h postdose FEV(1) for FSC compared with FP. Other efficacy measures were as follows: morning peak expiratory flow rate (PEF); transition dyspnea index; chronic respiratory disease questionnaire; chronic bronchitis symptom questionnaire; exacerbations; and other symptomatic measures.\n At Endpoint (ie, the last on-treatment, post-baseline assessment), treatment with FSC significantly (p < or = 0.012) increased the morning predose FEV(1) (165 mL) compared with SM (91 mL) and placebo (1 mL), and significantly (p < or = 0.001) increased the 2-h postdose FEV(1) (281 mL) compared with FP (147 mL) and placebo (58 mL). Improvements in lung function with FSC compared with FP and SM, and with FP and SM compared with placebo, as measured by the average daily morning PEF, was observed within approximately 24 h after the initiation of treatment, indicating an early onset of effect (p < or = 0.034). Compared with placebo, FSC significantly improved dyspnea, quality of life, and symptoms of chronic bronchitis. The incidence of adverse effects (except for an increase in oral candidiasis with FSC and FP) were similar among the treatment groups.\n Treatment with FSC (FP, 250 microg, and SM, 50 microg) twice daily substantially improved morning lung function and sustained these improvements for over a period of 24 weeks compared with FP or SM treatment alone in patients with COPD, with no additional safety concerns for the combination treatment vs that with the individual components.", "Treatment of chronic obstructive pulmonary disease (COPD) with inhaled and oral corticosteroids is common, although their exact role is unclear. Previous studies suggest these drugs may reduce decline in lung function in this group of patients. We report a study investigating the effect of inhaled beclomethasone diproprionate (BDP) on lung function and symptoms in a group of patients with COPD. Treatment was given for 2 years, and the decline in FEV1 in individual patients calculated over this period. Ninety-eight patients were randomized for the study, 59 completing 2 years of treatment. Patients withdrawn had more severe airflow obstruction. Decline in FEV1, measured both prior to and after bronchodilator, was less in patients receiving inhaled BDP, although the differences failed to reach statistical significance except in a subgroup of patients with more severe airflow obstruction. Exacerbation rates were also reduced by inhaled BDP, but again the differences failed to reach conventional levels of statistical significance. The results of this study are consistent with previous published work, but further insight into the long-term role of corticosteroids in COPD await the publication of large studies which have recently been completed. Although the changes seen in this study and others are numerically small, the rate of decline in FEV1 returned to normal levels expected from age-related decline, and hence such treatment combined with other strategies may well have a significant role in the long-term treatment of this condition.", "To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease.\n Double blind, placebo controlled study.\n Eighteen UK hospitals. Participants: 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV(1)) 50% of predicted normal. Interventions: Inhaled fluticasone propionate 500 microgram twice daily from a metered dose inhaler or identical placebo. Main outcome measures: Efficacy measures: rate of decline in FEV(1) after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events.\n There was no significant difference in the annual rate of decline in FEV(1 )(P=0.16). Mean FEV(1) after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P<0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P=0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P=0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v 19%, P=0.034).\n Fluticasone propionate 500 microgram twice daily did not affect the rate of decline in FEV(1) but did produce a small increase in FEV(1). Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.", "A significant minority of patients with COPD have favourable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side-effects. Long-term administration of inhaled steroids is a safe means of treatment. However, only a few studies have addressed the role of inhaled steroids in patients with COPD, with conflicting results.\n Forty-four patients with stable COPD were defined as 'responders to bronchodilators' (increase in FEV1 > or = 20% following administration of beta 2-agonist) (group A), and 124 as 'non-responders to bronchodilators' (group B). All patients were randomized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo, separated by 4 weeks when no medication was taken; were randomized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide, or 800 micrograms day-1 of inhaled budesonide plus placebo; and were randomized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo. All stages were performed in a double-blind cross-over design.\n Following administration of 800 micrograms day-1 of inhaled budesonide, there was an increase in the mean FEV1 from 1.40 +/- 0.20 to 1.92 +/- 0.22 L (P < 0.001) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment. The mean FEV1 did not change during the placebo period, or in group B in either treatments.\n Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD, and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation. There was no additional benefit in using a higher dose of inhaled budesonide or prednisone.", "Inhaled corticosteroids are often used in the treatment of stable chronic obstructive pulmonary disease (COPD), however, studies of these agents have had mixed results. Previous trials have often excluded subjects with bronchodilator response, have failed to evaluate effect on gas exchange, and have usually looked at only post- rather than prebronchodilator forced expiratory volume (FEV). Our objective was to better assess the efficacy of topical corticosteroids in the treatment of COPD. We used a prospective, randomized, double-blinded, placebo-controlled, crossover study at the Outpatient Department, Department of Veterans Affairs Medical Center. Thirty-six COPD patients with a mean (+/- SD) FEV1 of 1.10 +/- 0.43 L, with or without significant bronchodilator response participated in the study. Subjects received a 3-month course of inhaled fluticasone propionate (220 micro g/puff) or identical-appearing placebo by metered-dose inhaler at 2 puffs twice daily, followed by crossover to the alternative inhaler for an additional 3 months. Fluticasone treatment resulted in a higher prebronchodilator FEV1 (1.17 +/- 0.08 L [mean +/- SEM] versus 1.07 +/- 0.08 L, p = 0.001), a higher PaO2 (66.6 +/- 1.4 mmHg versus 63.6 +/- 1.6 mmHg, p = 0.002), and a better dyspnea score on the chronic respiratory questionnaire (3.70 +/- 0.18 versus 3.47 +/- 0.19, p = 0.03). A trend towards fewer exacerbations with fluticasone did not quite meet statistical significance (p = 0.11). Inhaled fluticasone over 3 months improved prebronchodilator airflow obstruction and oxygenation while decreasing dyspnea in moderate to severe COPD. Postbronchodilator FEV1 was not significantly changed.", "Withdrawal of corticosteroid is associated with a deterioration of health status in COPD. In this study the aim was to determine whether high dose inhaled corticosteroid improves quality of life in patients with COPD.\n In total, 38 male patients with moderate COPD were included in the study. Baseline quality of life scores were determined using a Turkish version of the St George's Respiratory Questionnaire (SGRQ). Patients were randomly divided into two groups. Group 1 consisted of 20 patients who received existing bronchodilator therapy plus inhaled corticosteroid (800 micro g budesonide) for 12 weeks, while 18 patients in group 2 received bronchodilator and placebo. The SGRQ was repeated after the treatment period.\n All patients were male and mean age was 67 +/- 8.2 years. Symptom, activity, impact, and total scores were assessed and a difference of four units with treatment was considered to be clinically significant. Total score and activity score were decreased by six units and eight units, respectively, in the placebo group while symptom and impact scores did not change significantly. Total scores and the three component scores improved significantly in the corticosteroid group compared to the placebo group (Deltatotal score: -22 in corticosteroid group, -6 in placebo group, P < 0.01).\n Inhaled corticosteroid improved quality of life scores in patients with COPD, without significant improvement in airflow obstruction parameters. Since improvement of health status is one of the important aims in COPD treatment, use of inhaled corticosteroids should be considered from this perspective.", "Inhaled corticosteroids (ICS) are effective in the treatment of asthma and markedly reduce the numbers of inflammatory cells in bronchial biopsies. However, the effect of ICS on the inflammatory profile of biopsies in smokers with chronic obstructive pulmonary disease (COPD) is unknown. We have performed a double-blind, placebo-controlled, randomized study to compare fluticasone propionate (FP) 500 microg twice daily via a dry powder inhaler and placebo (P) over a 3-month period in subjects with COPD. Fiberoptic bronchoscopy and bronchial biopsy was carried out at baseline and after the 3 months of treatment. Thirty-one subjects completed the trial and 30 paired biopsies were available for analysis. Compared with P (n = 14), subjects on inhaled FP (n = 16) had no significant reductions in the primary endpoints: CD8+, CD68+ cells, or neutrophils, considered to be of importance in COPD. However, there was a reduction in the CD8:CD4 ratio in the epithelium and of the numbers of subepithelial mast cells in the FP group. CD4+ cells were significantly raised in the P group in both subepithelium and epithelium. Symptoms significantly improved, and there were significantly fewer exacerbations in subjects on FP, compared to subjects on P. The data indicate that inhaled fluticasone does affect selected aspects of airway inflammation in COPD, and this may explain, in part, the decrease in exacerbations seen in long-term studies with fluticasone propionate.", "Combination therapy with corticosteroid and long-acting β(2)-agonists (LABA) in a single inhaler is associated with superior effects on airway function and exercise performance in COPD compared with LABA monotherapy. The physiological effects of adding inhaled corticosteroid monotherapy to maintenance bronchodilator therapy (long-acting anticholinergics and LABA singly or in combination) in COPD are unknown.\n This was a randomized, double-blind, placebo-controlled, crossover study (NCT00387036) to compare the effects of inhaled fluticasone propionate 500 μg (FP500) twice-daily and placebo (PLA) on airway function during rest and exercise, measured during constant work rate cycle exercise at 75% of maximum incremental cycle work rate, in 17 patients with COPD (FEV(1) ≤ 70% predicted).\n After treatment with FP500 compared to PLA, there were significant increases in post-dose measurements of FEV(1) (+115 mL, P = 0.006) and the FEV(1)/FVC ratio (+2.5%, P = 0.017), along with decreases in plethysmographic residual volume (-0.32L; P = 0.031), functional residual capacity (-0.30L, P = 0.033), and total lung capacity (-0.30L, P = 0.027) but no changes in vital capacity or inspiratory capacity (IC). Post-treatment comparisons demonstrated a significant improvement in endurance time by 188 ± 362 s with FP500 (P = 0.047) with no concomitant increase in dyspnea intensity. End-inspiratory and end-expiratory lung volumes were reduced at rest and throughout exercise with FP500 compared with PLA (P < 0.05).\n Inhaled FP500 monotherapy was associated with consistent and clinically important improvements in FEV(1), static lung volumes, dynamic operating lung volumes, and exercise endurance when added to established maintenance long-acting bronchodilator therapy in patients with moderate to severe COPD.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: \"Are inhaled corticosteroids able to slow down the decline in lung function (FEV1) in COPD?\"\n A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with \"asthmatic features\" were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 micrograms beclomethasone daily, six with 1600 micrograms budesonide daily, and eight with 800 micrograms beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV1 was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated.\n No baseline differences were observed (mean age 61 years, mean FEV1 45% predicted). The estimated two year difference in prebronchodilator FEV1 was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV1 showed a difference of +0.039 l/year (95% CI -0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group.\n This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV1 during two years of treatment with relatively high daily dosages of inhaled corticosteroids.", "Chronic bronchitis is associated with airways obstruction and inflammation. In order to determine whether aerosolized beclomethasone can modulate airway inflammation and diminish airway obstruction, subjects with chronic bronchitis performed spirometry and underwent bronchoalveolar lavage (BAL) before and after receiving 6 wk of therapy (five puffs four times a day) with either aerosolized beclomethasone (n = 20) or placebo (n = 10) in a double-blinded, randomized fashion. All subjects received aerosolized albuterol before each use of the study medications. Before BAL, the airways were visually assessed for the appearance of inflammation and assigned a score, the bronchitis index. BAL was performed by instilling five 20-ml aliquots of saline into each of three sites and pooling and separately analyzing the returns from the first aliquots to yield a \"bronchial sample.\" The bronchial lavages were repeated in an additional three sites to increase the volume of fluid available for analysis. The fluid was prepared for cytologic examination by cytocentrifugation. Albumin (as a measure of epithelium permeability) and lactoferrin and lysozyme (as measures of serous cell activity) were measured in unconcentrated BAL fluid by enzyme-linked immunosorbent assay, and concentrations in epithelial lining fluid were estimated using urea as an internal marker for dilution. After treatment, the beclomethasone group, but not the placebo group, showed improvement in FVC (p = 0.02), FEV1 (p = 0.002), and 25 to 75% forced expiratory flow (p = 0.006). Associated with the improvement in spirometry, the bronchitis index fell (13.5 +/- 1.0 versus 10.75 +/- 1.1, p = 0.02) in the beclomethasone-treated group, but not the placebo-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)", "An association between the sputum eosinophil count and the response to a 2 week course of prednisolone has previously been reported in patients with chronic obstructive pulmonary disease (COPD). Whether the response to inhaled corticosteroids is related to the presence of eosinophilic inflammation is unclear.\n A randomised, double blind, crossover trial of placebo and mometasone furoate (800 microg/day), each given for 6 weeks with a 4 week washout period, was performed in subjects with COPD treated with bronchodilator therapy only. Spirometric tests, symptom scores, chronic respiratory disease questionnaire (CRQ), and induced sputum were performed before and after each treatment phase.\n Ninety five patients were recruited of which 60 were randomised. Overall there were no treatment associated changes in forced expiratory volume in 1 second (FEV(1)), total CRQ, or sputum characteristics. After stratification into tertiles by baseline eosinophil count, the net improvement in post-bronchodilator FEV(1) increased with mometasone compared with placebo progressively from the least to the most eosinophilic tertile. The mean change in post-bronchodilator FEV(1) with mometasone compared with placebo in the highest tertile was 0.11 l (95% CI 0.03 to 0.19). This improvement was not associated with a fall in the sputum eosinophil count.\n An increased sputum eosinophil count is related to an improvement in post-bronchodilator FEV(1) following treatment with inhaled mometasone in COPD, but the improvement is not associated with a reduction in the sputum eosinophil count.", "Chronic obstructive pulmonary disease (COPD) results from a progressive decline in lung function, which is thought to be the consequence of airway inflammation. We hypothesized that antiinflammatory therapy with inhaled corticosteroids would slow this decline.\n We enrolled 1116 persons with COPD whose forced expiratory volume in one second (FEV1) was 30 to 90 percent of the predicted value in a 10-center, placebo-controlled, randomized trial of inhaled triamcinolone acetonide administered at a dose of 600 microg twice daily. The primary outcome measure was the rate of decline in FEV1 after the administration of a bronchodilator. The secondary outcome measures included respiratory symptoms, use of health care services, and airway reactivity. In a substudy of 412 participants, we measured bone density in the lumbar spine and femur at base line and one and three years after the beginning of treatment.\n The mean duration of follow-up was 40 months. The rate of decline in the FEV1 after bronchodilator use was similar in the 559 participants in the triamcinolone group and the 557 participants in the placebo group (44.2+/-2.9 vs. 47.0+/-3.0 ml per year, P= 0.50). Members of the triamcinolone group had fewer respiratory symptoms during the course of the study (21.1 per 100 person-years vs. 28.2 per 100 person-years, P=0.005) and had fewer visits to a physician because of a respiratory illness (1.2 per 100 person-years vs. 2.1 per 100 person-years, P=0.03). Those taking triamcinolone also had lower airway reactivity in response to methacholine challenge at 9 months and 33 months (P=0.02 for both comparisons). After three years, the bone density of the lumbar spine and the femur was significantly lower in the triamcinolone group (P < or = 0.007).\n Inhaled triamcinolone does not slow the rate of decline in lung function in people with COPD, but it improves airway reactivity and respiratory symptoms and decreases the use of health care services for respiratory problems. These benefits should be weighed against the potential long-term adverse effects of triamcinolone on bone mineral density.", "The aim of this study was evaluate the predictive value of a 2 week course of prednisolone on the effect of 6 months treatment with inhaled budesonide in patients with stable chronic obstructive pulmonary disease (COPD). Forty patients with stable COPD entered the study, and received prednisolone (37.5 mg o.d.) for 2 weeks. They were subsequently divided into steroid-irreversible and steroid-irreversible, using 15% of baseline as a dividing point. In each group patients were randomized to receive budesonide 400 micrograms b.i.d. or placebo for 6 months. During treatment with prednisolone, three patients dropped out because of side effects. Of the remaining 37, only two patients (5%) were reversible with prednisolone forced expiratory volume in 1s [(FEV1) > 15% of baseline], and among the steroid-irreversible, 26 patients were evaluated after 6 months treatment with either placebo or budesonide. No significant differences in spirometry values, symptoms, or number of exacerbations were found between these two groups. Reversibility with prednisolone is rarely seen in COPD. In outpatients with stable COPD and no signs of asthma or atopy, 2 weeks treatment with prednisolone seems to be of no value in choosing subsequent long-term therapy.", "This randomized controlled trial examined the benefits of combining an inhaled corticosteroid, fluticasone propionate (F), with an inhaled long-acting beta(2)-agonist, salmeterol (S), to treat the inflammatory and bronchoconstrictive components of chronic obstructive pulmonary disease (COPD). A total of 691 patients with COPD received the combination of F and S (FSC), S (50 mcg), F (500 mcg), or placebo twice daily via the Diskus device for 24 weeks. A significantly greater increase in predose FEV(1) at the endpoint was observed after FSC (156 ml) compared with S (107 ml, p = 0.012) and placebo (-4 ml, p < 0.0001). A significantly greater increase in 2-hour postdose FEV(1) at the endpoint was observed after treatment with FSC (261 ml) compared with F (138 ml, p < 0.001) and placebo (28 ml, p < 0.001). There were greater improvements in the Transition Dyspnea Index with FSC (2.1) compared with F (1.3, p = 0.033), S (0.9, p < 0.001), and placebo (0.4, p < 0.0001). The incidence of adverse effects (except for an increase in oral candidiasis with FSC and F) was similar among the treatment groups. We conclude that FSC improved lung function and reduced the severity of dyspnea compared with individual components and placebo.", "Chronic obstructive pulmonary disease is characterized by progressive airflow limitation and pulmonary inflammation. Inhaled corticosteroids (ICS) have been shown to be effective in the reduction of the number of exacerbations and the rate of deterioration in health status in patients with more advanced chronic obstructive pulmonary disease (COPD). Therefore current international guidelines recommend ICS for patients with severe COPD (FEV1 < 50%) with at least one exacerbation within the last year. We determined the short-term effect of the inhaled corticosteroid beclomethasone in HFA 134 formulation (Ventolair) on Health related Quality of Life (HRQOL), pulmonary function and the release of the cytokines Interleukin-10 (IL-10), Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF), Interferon-gamma (IFN-gamma) and Macrophage Inflammatory Protein-1alpha (MIP-1alpha) from peripheral blood monocytes of patients with COPD (n = 11) in a 12 week double blind cross over placebo-controlled study. Baseline lung function and the St. George Respiratory Questionnaire (SGRQ) were performed at the start and the end of each treatment phase. Monocytes were separated from blood at the end of each treatment phase. The treatment with Ventolair) resulted in an increase of PEF from 4.92 to 5.53 l/s and a decrease of RV% TLC (% predicted) values from 144.52 to 131.36. Inhaled HFA beclomethasone did not affect the cytokine release of IL-10, IFN-gamma, GM-CSF and MIP-1alpha. All cytokines were measured using commercially available Enzyme Linked Immun Sorbent Assay (ELISA) kits. The symptom score of the St. George Respiratory Questionnaire significantly decreased from 55.12 to 47.77 units in the active period compared to the placebo period after the treatment with HFA beclomethasone. The present study shows that a short-term treatment with inhaled steroid beclomethasone in fine particle HFA formulation decreases the hyperinflation and improves the PEF and the COPD symptoms." ]

[ "3524234", "9215204", "10642968", "2372330" ]

[ "Fetal acoustic stimulation testing. II. A randomized clinical comparison with the nonstress test.", "A randomized controlled trial of a new fetal acoustic stimulation test for fetal well-being.", "The predictive value of fetal acoustic stimulation.", "Effect of vibratory acoustic stimulation on the duration of fetal heart rate monitoring tests." ]

[ "Antepartum fetal heart rate testing, specifically the nonstress test, is of accepted value in the antenatal surveillance of high-risk pregnancies. Fetal rest-activity cycles coupled with arbitrary test intervals appear to lead to falsely nonreactive tests. Methods to alter fetal behavioral states have not been uniformly successful. A retrospective analysis of the adjunctive use of acoustic stimulation at our institution demonstrated a 50% reduction in the number of nonreactive tests. Consequently a prospective randomized clinical trial was undertaken to compare the standard nonstress test with the fetal acoustic stimulation test. Those patients randomized to the fetal acoustic stimulation test underwent transabdominal acoustic stimulation with a Model 5C electronic artificial larynx. The incidence of nonreactive tests was 14% in the control group and 9% in the study group (chi 2 = 11.09, p = 0.004). A significant reduction in testing time was also observed. The fetal acoustic stimulation test offers advantages over the traditional nonstress test by lowering the incidence of nonreactive tests and reducing testing time.", "Our purpose was to determine (1) whether a fetal acoustic stimulation test results in more palpable fetal movement compared with a mock test (control) and (2) whether palpated fetal movements after a fetal acoustic stimulation test are accompanied by a reactive nonstress test.\n In a randomized controlled trial we studied women seen in the labor and delivery suite for various indications. Women were excluded for multiple gestation, < 31 weeks' gestational age, treatment with magnesium sulfate or narcotics, or ruptured membranes. Informed consent was obtained from eligible women, who were then randomized to a test or control group. We placed an acoustic stimulator on the abdomen of each woman, but only the test group was stimulated. We assessed fetal movement by a grading system: 0 = no fetal movement felt by patient or tester, 1 = fetal movement felt by patient only, 2 = fetal movement felt by tester, 3 = visual movement seen by tester. A positive fetal acoustic stimulation test result was defined as one with any fetal movement felt or seen by the tester (grades 2 or 3). We then performed a nonstress test. We compared rates of a positive fetal acoustic stimulation test in the test and control groups with the chi 2 test. A p value < 0.05 was considered significant.\n We randomized 297 women to the test group and 280 women to the control (mock test) group. Of women tested with the fetal acoustic stimulation test. 81% had fetal movement by palpation or visualization (grades 2 or 3) compared with 19% of the control group (p < 0.0001, odds ratio 19.29, 95% confidence interval 12.42 to 30.07). Of the test group, 283 (95%) had a reactive nonstress test and 14 (5%) had nonreactive tests; the control group had 267 (95%) reactive and 13 (5%) nonreactive nonstress tests. Of 242 patients in the test group with a positive fetal acoustic stimulation test, 236 (98%) had a reactive nonstress test. Of those in the test group with fewer than three contractions per 10 minutes. 164 (89%) had a positive fetal acoustic stimulation test. Of these, 162 (99%) had a reactive nonstress test.\n The fetal acoustic stimulation test evokes significantly more palpated or visualized fetal movement than in controls. Palpated or visualized fetal movement after acoustic stimulation was almost always accompanied by a reactive nonstress test.", "To compare the predictive abilities, test duration times, and incidence of nonreactive results in the acoustic stimulation test (AST) and the nonstress test (NST).\n Four-hundred randomly selected patients, delivering within 7 days of a preceding test, were divided into two groups (group I: NST; group II: AST). In the AST group, fetal heart rate tracing were recorded for the first 5 minutes as a baseline recording. If the reactivity criterion was not met, transabdominal acoustic stimulation to the fetal head was performed. In the NST group, nonreactive tests were followed by a repeat NST. In both groups, nonreactive tests were followed by oxytocin challenge test (OCT) on the same day. Depressed 5-minute Apgar scores (< 7) and an umbilical arterial blood pH of < 7.2 were taken as indicators of fetal distress. Sensitivity, specificity, and predictive values of NST and AST were calculated and compared.\n The incidence of nonreactive tests was lower in the AST group. AST decreased the test duration time by 10.1 minutes. The sensitivity values were 87.5% in the NST group and 85.7 in the AST group; specificities of were found to be 94% for AST and 88% for NST. The negative predictive value was found to be 98% in each group, but the positive predictive value was 54.5% in the AST group and 38.8% in the NST group.\n AST offers benefits, by decreasing the incidence of nonreactive tests and reducing the test time. AST lowers the rate of false positives without changing the negative reliability of NST. It is a safe test and allows more efficient use of perinatal services.", "The ability of vibratory acoustic stimulation to shorten the duration of antepartum fetal heart rate monitoring was investigated by a randomized controlled trial. Vibratory acoustic stimulation did not shorten the overall duration of testing. This failure to improve the performance of antepartum monitoring appeared to result from prolonged accelerations, which complicated one third of the tests in which vibratory acoustic stimulation was employed. Further investigation is warranted using less profound methods of fetal stimulation." ]

[ "19809023" ]

[ "Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial." ]

[ "Sepsis is a common and severe complication in premature neonates, particularly those with very low birth weight (VLBW) (<1500 g). Whether lactoferrin, a mammalian milk glycoprotein involved in innate immune host defenses, can reduce the incidence of sepsis is unknown. In animal models, the probiotic Lactobacillus rhamnosus GG (LGG) enhances the activity of lactoferrin but has not been studied in human infants.\n To establish whether bovine lactoferrin (BLF), alone or in combination with LGG, reduces the incidence of late-onset sepsis in VLBW neonates.\n Prospective, multicenter, double-blind, placebo-controlled, randomized trial conducted in 11 Italian tertiary neonatal intensive care units. Patients were 472 VLBW infants enrolled from October 1, 2007, through July 31, 2008, and assessed until discharge for development of sepsis.\n Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 x 10(9) colony-forming units/d) (n = 151), or placebo (n = 168) from birth until day 30 of life (day 45 for neonates <1000 g at birth).\n First episode of late-onset sepsis, ie, sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid.\n Demographic, clinical, and management characteristics of the 3 groups were similar, including type of feeding and intake of maternal milk. Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups (9/153 [5.9%] and 7/151 [4.6%], respectively) than in the control group receiving placebo (29/168 [17.3%]) (risk ratio, 0.34; 95% confidence interval, 0.17-0.70; P = .002 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12-0.60; P < .001 for BLF plus LGG vs control). The decrease occurred for both bacterial and fungal sepsis. No adverse effects or intolerances to treatment occurred.\n Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates.\n isrctn.org Identifier: ISRCTN53107700." ]

[ "9745973", "14678373", "6541387", "3535621", "358381", "11044540", "3310369", "6367811", "6203818", "6685364", "2227611", "7006273", "2071809", "3287737" ]

[ "Randomized double-blind placebo-controlled multicenter evaluation of efficacy and dose finding of midodrine hydrochloride in women with mild to moderate stress urinary incontinence: a phase II study.", "A randomized crossover study to evaluate Ro 115-1240, a selective alpha1A/1L-adrenoceptor partial agonist in women with stress urinary incontinence.", "Urethral sphincteric insufficiency in postmenopausal females: treatment with phenylpropanolamine and estriol separately and in combination. A urodynamic and clinical evaluation.", "The effect of phenylpropanolamine on female stress urinary incontinence.", "The effects of long-term treatment with norephedrine on stress incontinence and urethral closure pressure profile.", "beta(2)-adrenergic agonists and pelvic floor exercises for female stress incontinence.", "Phenylpropanolamine in treatment of female stress urinary incontinence. Double-blind placebo controlled study in 24 patients.", "Treatment of motor urge incontinence with clenbuterol and flavoxate hydrochloride.", "[Conservative therapy of female stress incontinence. Double-blind study with the alpha-sympathomimetic midodrin].", "Stress incontinence in females: treatment with phenylpropanolamine. A urodynamic and pharmacological evaluation.", "Effect of combined treatment with phenylpropanolamine and estriol, compared with estriol treatment alone, in postmenopausal women with stress urinary incontinence.", "Effects of oestradiol and combined norephedrin and oestradiol treatment on female stress incontinence.", "Pelvic muscle exercise for stress urinary incontinence in elderly women.", "Norfenefrine in the treatment of female stress incontinence. A double-blind controlled trial." ]

[ "Midodrine is a potent and selective alpha1-receptor agonist and its potential to increase urethral closure pressure could be useful in the treatment of female stress incontinence. The aim of this randomized double-blind placebo-controlled multicenter study was to evaluate the efficacy and safety of midodrine for the treatment of stress urinary incontinence. The primary criterion of efficacy was the maximum urethral closure pressure at rest. Voiding diaries, symptom and incontinence questionnaires and patient/investigator global assessment were also used to evaluate its efficacy. After 4 weeks of treatment no significant changes in MUCP were found. The global assessment by the patient and investigator did indicate that patients on active treatment had a more positive assessment than the placebo group. In conclusion, midodrine did not cause significant improvements in urodynamic parameters, but there were subjective improvements in some of the patients in the treated groups. Furthermore midodrine was well tolerated.", "To investigate the potential therapeutic benefits of the selective alpha1A/1l-adrenoceptor partial agonist Ro 115-1240 in women with mild-to-moderate stress urinary incontinence (SUI).\n Thirty-seven women with mild-to-moderate SUI were enrolled in a randomized, placebo-controlled crossover study. Patients received 1.5 mg Ro 115-1240 twice daily or matching placebo for 2 or 4 weeks. Voiding diaries were used to record the number of SUI episodes, urge incontinence episodes and pads used. Sitting blood pressures and heart rate were recorded at each visit.\n Ro 115-1240 was associated with a significantly lower mean weekly number of SUI episodes than placebo (8.4 vs 6.0; P= 0.0079), a 28% relative improvement over placebo. There was also a significantly lower mean number of pads used and wet pads changed/week with Ro 115-1240 than with placebo (P = 0.0055 and 0.0066, respectively). The most frequently reported treatment-emergent adverse events were scalp tingling, headache, chills, piloerection, and pruritus. Generally these events were transient and mild to moderate. There was a slightly lower mean sitting heart rate with Ro 115-1240 than with placebo, but no difference in mean systolic or diastolic blood pressure between treatments.\n This study suggests that selective alpha1A/1l-adrenoceptor partial agonists have the potential to improve the symptoms of SUI with little or no cardiovascular effect. These results are encouraging and a randomized controlled trial of Ro 115-1240 in a larger population with SUI is warranted to substantiate these findings.", "A randomized open comparative cross-over trial was carried out in 20 postmenopausal women, mean age 69 years, suffering from urinary incontinence due to urethral sphincteric insufficiency. They were treated with phenylpropanolamine (PPA) 50 mg p.o. twice daily or estriol vaginal suppositories 1 mg daily separately and in combination for periods of 4 weeks. Urodynamic investigations were carried out before and after each period of treatment. Both PPA and estriol increased the maximal urethral closure pressure and the continence area significantly compared to the initial values, but combined treatment was substantially more effective. The functional urethral length increased significantly while on estriol. No significant change was registered in the bladder pressure or in the pressure transmission ratio. PPA was clinically more effective than estriol, but not sufficient to obtain complete continence. With combined treatment 8 patients became completely continent, 9 were considerably improved and only 1 patient remained unchanged. 2 patients dropped out of the study because of side effects. Combined treatment with PPA and estriol represents a recommendable treatment to postmenopausal women with urinary incontinence due to urethral sphincteric insufficiency.", "In a randomized double-blind manner, 43 women with grade I and II stress urinary incontinence were treated with either phenylpropanolamine p.o. 50 mg twice daily (Rinexin, 1 tablet b.i.d.) or placebo during two weeks. Urethral CO2 profilometry, with recording of maximum urethral closure pressure (MUCP) and functional urethral length (FUL), and subjective response were considered for effect evaluation. The subjective response of Rinexin was highly significant (p = 0.01) above that of placebo. Clinical improvement was reported by 15 of 21 women on Rinexin and by 8 of 22 women on placebo. A significant increase in MUCP, 14%, was registered in women on Rinexin treatment. This increase was more pronounced in the grade I than in the grade II incontinent women. No statistically significant correlations were obtained between subjective response and increase in MUCP. An increase in FUL was recorded in both two treatment groups, but no statistically significant difference between them was obtained. Adverse drug reactions were rare. No changes in blood pressure occurred. Based on the present study, Rinexin (1 tablet b.i.d.) is an effective and safe medication for female grade I and II stress incontinence and is also recommended as adjunctive therapy to physiotherapy before Teflon injection or operation.", "Twenty-five women with stress incontinence of urine were given an alpha-adrenoceptor stimulating agent (norephedrine) and a placebo during respective 14-day periods according to a double-blind cross-over schedule. The results were classified as the patient's own assessment of therapeutic effect and as change in urethral closure pressure profile measured by a microtransducer catheter. Norephedrine had a significant therapeutic effect on the symptom stress incontinence and produced significant increase in maximum urethral pressure and maximum urethral closure pressure in the lithotomy and the erect position. Reduction of incontinence was associated with increase in maximum urethral closure pressure. The sum therapeutic effect was of moderate degree.", "We compared beta(2)-adrenergic agonist therapy with clenbuterol (DT) and physiological therapy (PT) in a randomized study to establish the first line therapy for stress incontinence (SI).\n The clinical efficacy of DT (group A), PT (group B), and a combination of DT and PT (group C) was investigated in 61 patients with SI by means of a 12-week randomized controlled study. The frequency and volume of SI and the patients' own impressions were used as the basis for the assessment of efficacy.\n The SI improvement rates in groups A, B, and C were 76.9, 52.6, and 89. 5%, respectively (P=0.0361). A significant therapeutic effect on the frequency of SI was observed in group B and group C at 2 weeks after the start of treatment (both P<0.05), and in all groups at 6 weeks (all P<0.01). The efficacy rates based on the patients' own impressions in groups A, B, and C were 84.6, 31.6, and 68.4%, respectively (P=0.0064).\n The beta(2)-adrenergic agonist appeared to be clinically useful as a drug of choice for SI.", "Twenty-four women with stress urinary incontinence of slight to moderate grade were treated with phenylpropanolamine (PPA), po 50 mg twice daily, and placebo for periods of two weeks according to randomized double-blind cross-over schedule. A significant increase in maximum urethral closure pressure (MUCP) was found after treatment with PPA compared to placebo, but functional urethral length was unchanged. Number of leakage episodes were significantly reduced during PPA treatment, but micturition frequency was unchanged. Fourteen women preferred PPA, 4 preferred placebo, and 6 considered PPA and placebo to be ineffective. The scored improvements obtained by PPA were highly significant when tested against the scored placebo effect. There was a significant correlation between subjective assessment and improvement in number of leakage episodes and increase of MUCP. Plasma-PPA levels showed no significant correlation with any of the effect variables. Adverse reactions were few and negligible.", "A controlled double-blind trial is reported of the parasympatholytic drug, flavoxate hydrochloride, and the new sympathomimetic drug, clenbuterol, in the treatment of 39 women with motor urge incontinence. The clinical results and the urodynamic findings of urethro-cystomanometry after therapy showed clenbuterol to be very effective with few side effects.", "Midodrine, an alpha-adrenergic agent, was tested in a double-blind randomized fashion in 50 female patients suffering from stress incontinence. 61,5% of the patients receiving midodrine became completely continent, 23,1% improved and 15,4% were considered failure. The results obtained, have been statistically significant.", "23 females, mean age 53 years, with genuine stress incontinence were treated with phenylpropanolamine (PPA), 50 mg twice daily, versus placebo. Simultaneous urethrocystometry with recording of the transmission of increased abdominal pressure to the bladder and the urethra was carried out, and serum concentration of PPA measured and related to subjective effect, effect on the maximal urethral closure pressure (MUCP) and on the pressure transmission ratio. 3 patients were excluded, 1 because of side effects, and 2 were dropouts. 12 patients reported improvement while on PPA, but none became continent. 3 patients improved on placebo. The remaining patients were unchanged. A plasma level of PPA of more than 150 ng/ml seemed necessary to obtain an effect; this level was reached after approximately 90 min after intake of 50 mg. Objectively a rise in MUCP was recorded, but there was no correlation between serum concentration and the increase in MUCP. An improvement of the pressure transmission ratio was also recorded.", "Twenty-nine postmenopausal women with slight to severe stress urinary incontinence and estrogen deficiency symptoms in the urogenital tract were treated with estriol, p.o. 4 mg once daily, and either phenylpropanolamine (PPA), p.o. 50 mg twice daily, or placebo for periods of 6 weeks according to a randomized double-blind crossover schedule. At urodynamic recordings the maximum urethral closure pressure increased by 22% with combined treatment (p less than 0.001) and an additional effect of PPA to estriol was shown (p = 0.022). The pressure transmission ratio increased, by about 15%, with both treatments (p less than 0.07). The number of leakage episodes was reduced by 28% with combined treatment (p = 0.007), but not with estriol alone (p = 0.08). Both combined treatment and estriol alone reduced significantly (p less than 0.01) the urinary incontinence complaints. Twelve women (43%) preferred combined treatment, while 7 (25%) preferred estriol alone. In women with initially slight to very severe urine loss, combined treatment reduced also (p = 0.02) the amount of urine loss, measured at a standardized physical stress test. Signs of estrogen deficiency in vulva, vagina and urethra were reduced, 75% (p less than 0.001) or 65% (p = 0.001) with estriol given in combination with PPA or alone. Maturation index of both urethral and vaginal epithelium displayed significant changes. It is concluded that the combined treatment, PPA + estriol, by affecting both the muscular and mucosal factor of the urethra, is more effective than estriol alone for treatment of female stress urinary incontinence in the postmenopausal ages.", "Thirteen postmenopausal stress incontinent women were treated with oestradiol for one month, and then with oestradiol in combination with norephedrine or placebo according to a double-blind, cross-over schedule. Therapeutic results were assessed by measuring changes in urethral closure pressure profile (UCPP) by means of micro transducer catheters, and by the patient's subjective assessment of the effects. Oestradiol had no effect on the symptom stress incontinence or on UCPP. Norephedrine in combination with oestradiol had a statistically significant therapeutic effect on the symptoms of the patients, and increased UCPP. However, the combination did not increase UCPP more than did norephedrine alone.", "To compare pelvic muscle exercise to pharmacologic treatment of stress urinary incontinence, the most common cause of urine leakage reported by community-living elderly women.\n Convenience sample of 157 community-living women, aged 55 to 90 years, after completion of a comprehensive diagnostic evaluation.\n Eighty-two subjects were randomly assigned to the exercise protocol (with a 34% attrition rate). Pelvic muscle exercises were taught and monitored for 6 months. Phenylpropanolamine hydrochloride was given to the other group in a dose of 50 mg a day, increasing to 50 mg twice a day.\n Treatment outcomes (subjective improvement, self recorded frequency of wetting) were equally satisfactory in both groups. The response to exercises was as good in 5 months as in 6. It was also as good when the minimum recommended number of exercises per day was 80 as when it was 125.\n Among those completing the protocol, pelvic exercises were beneficial in reducing stress incontinence, and the benefit was comparable to that produced by phenylpropanolamine.", "Forty-four consecutive patients with genuine stress incontinence were treated with norfenefrine 15-30 mg t.i.d. in a 6-week, double-blind and parallel, placebo-controlled study. Subjectively, 52% were improved and 26% became continent during norfenefrine treatment. Objectively (stress test), 30% became continent and the maximum urethral closure pressure increased 10% which was statistically significant. These results, however, were not statistically different from those of placebo treatment. Simultaneously, subjective and objective improvement was seen more often in patients given norfenefrine compared to placebo (p less than 0.1). In patients with most severe incontinence according to urodynamic criteria the effect of norfenefrine was statistically significantly better than placebo. A low incidence of side effects was observed and no differences between norfenefrine and placebo were found. It is concluded that norfenefrine may be of value in the treatment of female stress incontinence." ]

[ "17010115", "12391951" ]

[ "Cluster randomised trial of an active, multifaceted educational intervention based on the WHO Reproductive Health Library to improve obstetric practices.", "Primary care guidelines on consultation practices: the effectiveness of computerized versus paper-based versions. A cluster randomized controlled trial among newly qualified primary care physicians." ]

[ "We conducted a trial to evaluate the effect of an active, multifaceted educational strategy to promote the use of the WHO Reproductive Health Library (RHL) on obstetric practices.\n Cluster randomised trial. The trial was assigned the International Standardised Randomised Controlled Trial Number ISRCTN14055385.\n Twenty-two hospitals in Mexico City and 18 in the Northeast region of Thailand.\n The intervention consisted primarily of three interactive workshops using RHL over a period of 6 months. The focus of the workshops was to provide access to knowledge and enable its use. A computer and support for using both the computer and RHL were provided at each hospital. The control hospitals did not receive any intervention.\n The main outcome measures were changes in ten selected clinical practices as recommended in RHL starting approximately four to six months after the third workshop. Clinical practice data were collected at each hospital from 1000 consecutively delivered women or for a 6-month period whichever was reached sooner.\n The active, multifaceted educational intervention we employed did not affect the ten targeted practices in a consistent and substantive way. Iron/folate supplementation, uterotonic use after birth and breastfeeding on demand were already frequently practiced, and we were unable to measure external cephalic version. Of the remaining six practices, selective, as opposed to routine episiotomy policy increased in the intervention group (difference in adjusted mean rate = 5.3%; 95% CI -0.1 to 10.7%) in Thailand, and there was a trend towards an increased use of antibiotics at caesarean section in Mexico (difference in adjusted mean rate = 19.0%; 95% CI: -8.0 to 46.0%). There were no differences in the use of labour companionship, magnesium sulphate use for eclampsia, corticosteroids for women delivering before 34 weeks and vacuum extraction. RHL awareness (24.8-65.5% in Mexico and 33.9-83.3% in Thailand) and use (4.8-34.9% in Mexico and 15.5-76.4% in Thailand) increased substantially after the intervention in both countries.\n The multifaceted, active strategy to provide health workers with the knowledge and skills to use RHL to improve their practice led to increased access to and use of RHL, however, no consistent or substantive changes in clinical practices were detected within 4-6 months after the third workshop.", "To compare the effects of computerized and paper-based versions of guidelines on recently qualified physicians' consultation practices.\n Two arm cluster randomized controlled trial. Physicians were randomized to receive computerized or textbook-based versions of the same guidelines for a 4-week study period. Physicians' compliance with guideline recommendations about laboratory, radiological, physical and other examinations, procedures, nonpharmacologic and pharmacologic treatments, physiotherapy, and referrals were measured by case note review.\n There were 139 recently qualified physicians working in 96 primary healthcare centers in Finland who participated in the study. Data on 4,633 patient encounters were abstracted, of which 3,484 were suitable for further analysis. Physicians' compliance with guidelines was high (over 80% for use of laboratory, radiology, physical examinations, and referrals). There were no significant differences in physicians' consultation practices in any of the measured outcomes between the computerized and textbook group.\n Guidelines are a useful source of information for recently qualified physicians working in primary care. However, the method of presentation of the guidelines (electronic or paper) does not have an effect on guideline use or their impact on decisions. Other factors should be considered when choosing the method of presentation of guidelines, such as information-seeking time, ease of use during the consultation, ability to update, production costs, and the physician's own preferences." ]

[ "769913", "6995193", "4348437", "705420", "322823", "4939601", "8014510", "7018164", "7000949", "5015963", "9524997", "9132982", "1092425", "4600865", "4591199", "10819810", "356372", "1411848", "9166304", "1098732", "1103022", "14089304", "4849985", "6350957", "1396198" ]

[ "Two-day treatment of trichomoniasis in the female. Comparison of metronidazole and nimorazole.", "A double-blind controlled clinical trial of carnidazole and tinidazole in the treatment of vaginal trichomoniasis.", "Treatment of vaginal trichomoniasis with a new anti-protozoal compound ( -chloromethyl-2-methyl-5-nitro-1-imidazole-ethanol).", "Single-day treatment of trichomonas vaginitis with low dose of ornidazole.", "First experiences with single-dose treatment of vaginal trichomoniasis with carnidazole (R 25831).", "Nitrimidazine compared with metronidazole in the treatment of vaginal trichomoniasis.", "A double-blind placebo-controlled trial of single-dose intravaginal versus single-dose oral metronidazole in the treatment of trichomonal vaginitis.", "A double-blind study of the value of treatment with a single dose tinidazole of partners to females with trichomoniasis.", "Double blind comparative study of tinidazole and ornidazole as a single dose treatment of vaginal trichomoniasis.", "Nitrimidazine (Naxogin) compared with metronidazole (Flagyl) in the treatment of trichomonal vaginitis.", "A pilot study of metronidazole vaginal gel versus oral metronidazole for the treatment of Trichomonas vaginalis vaginitis.", "Multicenter comparison of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine hydrochloride, and allantoin in the treatment of symptomatic trichomoniasis.", "Trichomonal vaginitis. A 24-hr regimen of nimorazole compared with a 7-day regimen of metronidazole.", "[Controlled research on the treatment of trichomonas vaginitis by nimorazol (nitrimidazine) or metronidazole].", "Nimorazole compared with metronidazole in the treatment of vaginal trichomoniasis.", "A randomized trial of intravaginal nonoxynol 9 versus oral metronidazole in the treatment of vaginal trichomoniasis.", "[Single-dose treatment with ornidazole (Tiberal) in vaginal trichomoniasis. A controlled clinical study in general practice].", "Split-dose metronidazole or single-dose tinidazole for the treatment of vaginal trichomoniasis.", "The minimum single oral metronidazole dose for treating trichomoniasis: a randomized, blinded study.", "Treatment of trichomoniasis in the female. A comparison of metronidazole and nimorazole.", "[Local treatment of vaginitis due to T. vaginalis. Comparative studies on methyl-partricin and metronidazole].", "METRONIDAZOLE AND TRICHOMONAL VAGINITIS; REPORT OF A DOUBLE-BLIND CLINICAL INVESTIGATION OF 450 WOMEN.", "[Therapy of combined vaginal infections with Trichomonas vaginalis and Blastomycetes. A controlled double-blind comparison of Metronidazole and Clotrimazole].", "Single oral dose of ornidazole in women with vaginal trichomoniasis.", "Treatment of symptomatic trichomoniasis among adult women using oral nitroimidazoles." ]

[ "A comparison has been made of the efficiency of a 2-day course of metronidazole (Flagyl) with that of a similar course of nimorazole (Naxogin) in the treatment of trichomoniasis. Of the 105 consecutive patients treated, 72 were finally included in the study (38 on metronidazole and 34 on nimorazole). Follow-up tests indicated an overall cure rate of 84-3 per cent. in those given Flagyl and 85-3 per cent. in those given Naxogin. Consorts were treated in just over 55 per cent. of cases in both groups. An attempt has been made to classify the recurrences as either 'primary' treatment failures or re-infections. Although both drugs were effective in the majority of cases, 'primary' treatment failure appeared to be commoner in the group receiving metronidazole. It is emphasized that the total dose of metronidazole was substantially lower than that recommended by the manufacturers.", "A double-blind controlled clinical trial of the new, not yet commercially available drug, carnidazole and tinidazole, was carried out in 77 women with a proven vaginal trichomoniasis. 39 patients and their sexual partners received a single dose of 2 g of carnidazole and the other 38 couples were treated in the same manner with tinidazole. The cure rate was 100% and 95% respectively. The side-effects were higher in the carnidazole group, although they were mild and well-tolerated by the patients and their partners. The history of the disease and its treatment are also briefly reviewed.", "nan", "A total of 107 cases of trichomonas vaginitis were treated with different regimens of ornidazole. The overall success rate of the treatment assessed by wet smear and clinical signs after three days in 68 cases was 98.5%. The side effects were mild and of short duration. These were noted in 14.7% of the assessable cases. No significant differences were seen in the success rate between the three drug regimens and the preliminary conclusions of the trial are that ornidazole is safe and effective in the treatment of trichomonas vaginitis in Korean women with an oral dose of 1.0 gm, 1.0 gm plus 0.5 gm intravaginally or 2.0 gm given in a single day.", "This paper reports the results of treating 152 women with carnidazole, a new trichomonacidal drug. They were divided into two groups. The first comprised 91 patients who were treated with 2 g, while the second group comprised 61 patients who were treated with 1-5 g carnidazole in a single oral dose. Defaulter rates were 6-6% for the first group and 13-1% for the second. Of the remaining 85 patients in the first group, 76 (89-5%) were negative at the first follow-up one to three weeks after treatment, three (3-5%) were considered to be treatment failures, and six (7-0%) were considered to be reinfected. Of 53 women treated with 1-5 g, 39 (73-6%) were negative at first follow-up, eight (15-1%) were considered to be treatment failures, and six (11-3%) were considered to be reinfected. The difference between the number of patients cured in both groups is statistically significant. Fourteen patients experienced side-effects, but these were of little significance. Carnidazole given in a single oral dose of 2 g in 16 women did not cause consistent changes in any of the haematological and biochemical parameters studied.", "A new substituted nitroimidazole, nitrimidazine (Naxogin), is compared with the established drug, metronidazole (Flagyl), for the treatment of vaginal trichomoniasis in a randomized double-blind trial. Nitrimidazine cured 39 (68%) out of 57 patients and showed no undesirable effects other than nausea in one patient. Metronidazole cured 51 (89%) out of 57 patients and also caused nausea in one patient; this cure rate corresponds with that previously reported in other trials. In the recommended dosage nitrimidazine is inferior to metronidazole, but is sufficiently effective to be useful in cases of intolerance to metronidazole.", "Since metronidazole is a mutagen in vitro, there is concern about the widespread systemic use of this drug in women with trichomoniasis, particularly those who are pregnant. A randomized, double-blind, placebo-controlled trial compared a single 2-g intravaginal dose of metronidazole cream with a single 2-g oral dose of metronidazole in patients with a culture positive for Trichomonas organisms. Of the 302 preenrollment cultures completed, 94 (31%) were positive. Sixty-one patients were enrolled in the study. Each received either oral placebo and intravaginal metronidazole or intravaginal placebo and oral metronidazole. Follow-up cultures were done on posttreatment day 3-5. Of the 53 evaluatable patients, 14 (50%) of 28 in the intravaginal group and 22 (88%) of 25 in the oral group were microbiologically cured (P = .0037). Single-dose intravaginal metronidazole is inferior to single-dose oral metronidazole and cannot be relied on as an alternative therapy.", "Tinidazole 2 g single oral dose was given to 137 females with positive trichomonal cultures. On a random basis the same dose of tinidazole was given to half the sexual partners, and matching placebo to the other half. One to two weeks after treatment 5 females had positive cultures, indicating a primary cure rate of 96.4%. At an average of 2 months after treatment and 6 weeks after resuming sexual activity, 118 females were reexamined; 17 had a positive culture, giving an overall relapse rate of 14.4%. The relapse rate with tinidazole-treated partner was 5.1%, and with placebo-treated partner 23.7% (p equals 0.01). The definitive cure rate after a single dose of tinidazole 2 g was in females with treated partner 91.8% and with untreated partner 72.6%. It is concluded that a single dose of tinidazole is an effective treatment for females with trichomoniasis but to avoid relapse it is necessary to treat the sexual partner too.", "nan", "nan", "Trichomonas vaginalis is a common sexually transmitted pathogen. In the United States, oral metronidazole is the only officially sanctioned treatment option.\n This study was undertaken to compare the efficacy and safety of 0.75% metronidazole vaginal gel with that of oral metronidazole for the treatment of trichomonal vaginitis.\n Women with trichomoniasis were enrolled in this randomized, open-label pilot study of 0.75% metronidazole vaginal gel twice daily for 7 days compared with 7 days of generic oral metronidazole, 250 mg, three times daily. Patients were seen for follow-up visits 5 to 7 days and 21 to 28 days after the last dose of medication.\n Using culture for test of cure, trichomonal infection was eliminated in all 15 women treated with oral metronidazole and 7 (44%) of 16 women treated with intravaginal metronidazole. Adverse events were similar, except that there were more taste-related adverse events in the oral metronidazole group. Significant reductions in genitourinary symptoms were seen in both the oral and intravaginal groups.\n This study has shown that 0.75% metronidazole vaginal gel is not effective as a single agent for the treatment of trichomoniasis. Future studies may define a role for metronidazole gel for symptomatic relief in patients intolerant of oral medication or as adjunctive treatment with oral metronidazole for the management of patients infected with metronidazole-resistant strains of T. vaginalis.", "Trichomonas vaginalis is a common vaginal pathogen. Oral metronidazole is the drug of choice for the treatment of trichomoniasis. Oral metronidazole, however, may cause unpleasant side effects and is contraindicated during the first trimester of pregnancy. In vitro studies and preliminary clinical data have suggested that intravaginal clotrimazole may be effective against this pathogen.\n To compare the efficacy of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine, and allantoin (AVC suppositories) in the treatment of women with symptomatic trichomoniasis.\n In a multicenter, open-label trial conducted in 1982 and 1983, 168 symptomatic women with microscopically evident vaginal trichomoniasis were randomized to receive any of 2 g of metronidazole as a single oral dose, two 100-mg clotrimazole vaginal tablets once a day for 7 days, or vaginal suppositories containing 1.05 g of sulfanilamide, 14 mg of aminacrine hydrochloride, and 140 mg of allantoin (AVC suppositories) twice a day for 7 days. Wet mounts and cultures were repated at 1 to 2 and 4 to 6 weeks after completion of treatment.\n The number of patients who had positive cultures after treatment were 40/45 (88.9%) in the clotrimazole group, 35/43 (81.4%) in the AVC suppository group, and 9/45 (20%) in the metronidazole group (P < 0.001). All treatments were associated with a reduction in reported symptoms. Oral metrohidazole was more effective in reducing symptoms than either of the topical preparations. Adverse events, mostly mild or moderate in severity, were reported by 7 (14.6%) of 48 patients who had received oral metronidazole and 4 (7.8%) of 51 women who used AVC suppositories. There were no adverse events reported by the 50 women who used clotrimazole vaginal tablets.\n Oral metronidazole was more effective in eradicating T. vaginalis than clotrimazole vaginal tablets or AVC vaginal suppositories. All three regimens reduced symptoms; oral metronidazole was more effective in reducing symptoms than either topical preparation.", "A 24-hr regimen of nimorazole (1 g. orally at 12-hrly intervals for three doses) was compared with metronidazole (200 mg. three times daily for 7 days) in the treatment of trichomonal vaginitis. The two treatment schedules were given to alternate patients, pregnant women being excluded. One hundred cases were treated on each schedule; roughly one-fifth of the patients in each group defaulted. There were no observed failures with either schedule. The reasons for these exceptionally good results are discussed.", "nan", "nan", "This study was undertaken to investigate the efficacy of nonoxynol 9 suppositories in the treatment of vaginal trichomoniasis.\n In this prospective comparison trial 46 women with documented motile trichomonads found on a wet preparation were randomly assigned to one of two treatment arms: (1) a single oral dose of 2 g metronidazole and (2) a single 150-mg nonoxynol 9 suppository placed intravaginally for 3 consecutive nights. Cure was determined by a repeated wet preparation examination. After its first year, the study was terminated because of the poor efficacy of the nonoxynol 9 suppositories.\n Results were available for 33 patients. Three of 17 patients treated with nonoxynol 9 had negative wet preparation results at retest (17.6% cure rate). All 16 patients treated with metronidazole had negative wet preparation results (100% cure rate). All women with nonoxynol 9 failures who were evaluated after treatment with 2 g metronidazole had negative wet preparation results.\n Intravaginal nonoxynol 9 at the tested dose and by the tested method of delivery was not an effective cure for vaginal trichomoniasis.", "nan", "In a double-blind, randomized, controlled trial, efficacy and safety of a single-day split dose of 1.6 g of metronidazole were compared with a single 2-g dose of tinidazole in the treatment of vaginal trichomoniasis. Women with symptomatic vaginal trichomoniasis were randomly assigned to one of the two treatment groups. There were 67 women in the group treated with the single-day split dose and 65 in group treated with the single dose. There was no significant difference between the two groups in terms of clinical characteristics (age, weight, and length of follow-up period). The cure rates, using trypticase yeast extract iron serum (TYI) medium to confirm microbiologic cure, were 98.5% and 100% for the groups treated with a single-day split dose and with a single dose, respectively. The side effects were minimal and did not warrant any treatment. The differences in the results were not statistically significant. We recommend that the single-day split dose of 1.6 g of metronidazole regimen be given as an alternative drug for vaginal trichomoniasis. Its advantages include being highly effective, significantly less expensive, and with minimal side effects.", "To identify the minimum effective single oral dose of metronidazole for trichomoniasis.\n Women attending an inner-city sexually transmitted disease clinic who had Trichomonas vaginalis vaginitis diagnosed by microscopy were recruited for this randomized, double-blind study. Subjects were given a 0.5-, 1-, 1.5-, or 2-g single oral dose of metronidazole, taken under direct observation. Demographic information, symptoms, and clinical findings were collected from patient interviews, and physical examinations were conducted at the time of enrollment and at the follow-up visit. The primary outcome measure was treatment success at the follow-up visit, established by negative culture and microscopy.\n Three (1.8%) of the 167 women enrolled were excluded because of vomiting after taking metronidazole, and 66 (40%) of the 164 remaining subjects did not return for the follow-up visit. No associations were found between the proportion of subjects lost to follow-up and the characteristics of these subjects across assignment groups. The treatment success ratio was highest in subjects who received the 1.5-g dose (23, 85%), followed by the 2-g (16, 84%), 1-g (18, 62%), and the 0.5-g dose (8, 35%).\n A single 1.5-g dose of metronidazole has efficacy equivalent to a single 2-g dose for the treatment of T vaginalis vaginitis.", "The effectiveness of metronidazole (Flagyl) and nimorazole (Naxogin) has been compared by using these drugs in the recommended dosage in alternate patients in a series of 218 consecutive cases of vaginal trichomoniasis. Follow-up tests in 100 patients treated with metronidazole and 97 treated with nimorazole indicated cure-rates of 95 and 82 per cent. respectively. Male consorts were examined and given treatment on epidemiological grounds in about 70 per cent. of both treatment groups. Both drugs were free from significant side-effects. The causes of treatment failure in trichomoniasis are discussed and the desirability of relating dosage to the patient's body-weight is suggested. This factor may be especially important in deciding the dosage given on epidemiological grounds to the male consorts. It may also be an important advantage in the current trend of treating trichomoniasis in both sexes with larger doses over a much shorter time.", "nan", "nan", "nan", "Fifty-nine women with trichomonal vaginitis were randomly allocated to receive treatment with a single oral dose of either 0.5, 1.0, or 1.5 g of ornidazole. One week after treatment, a parasitologic cure was observed in 100% of patients treated with 1.5 g, in 95% of patients treated with 1.0 g, and in 65% of patients given 0.5 g. At the one-month follow-up visit, the cure rate remained at 100% for the 1.5-g dose group but dropped to 85 and 45% in the 1.0- and 0.5-g dose groups, respectively. The disappearance of symptomatic complaints was also dose related: the clinical cure was 100, 85, and 40% at the first follow-up visit and 89, 80, and 30% at the second follow-up visit. Adverse effects of mild or moderate severity were reported by 13 patients. These were encountered mostly in the 1.5- and the 1.0-g dose groups. The most frequent adverse effects were dizziness and gastrointestinal distress. Laboratory safety test did not reveal any significant toxicity. This study confirms that single-dose treatment of trichomoniasis with an oral dose of 1.5 or 1.0 g of ornidazole is effective and well tolerated.", "Successful treatment of infections with Trichomonas vaginalis (TV) is difficult because of many confounding factors such as poor abstinence from sex during chemotherapy, lack of standardised chemotherapy, difficulties in understanding transmission patterns and low detection rates among infected individuals. The purpose of this study was to establish the present efficacy of the available drugs at their recommended single or double dosages for Kenya. Adult symptomatic females (age 17-39 years) with positive High Vaginal Swabs but without pregnancy were recruited into the study; and asked to swallow one of the following medicine: nimorazole 2G (Naxogin Farmitalia Carlo Erba, Italy), nimorazole 4G in two equally divided doses 24 hours apart (2GBD), nimorazole 3G, tinidazole 2G (Fasigyn, Pfizer Ltd) and ornidazole 1.5G (Tiberal, Roche, Switzerland). All patients were reviewed 48 hours after the drugs administration and 24 hours after the last dose for the group which received nimorazole 2GBD. 153 patients were recruited into the study. 121 came for follow up out of which 49 were dropped from the study for involvement in sexual intercourse leaving only 72 for the final analysis. Clinical cure was 100% for the group receiving nimorazole 2GBD and nimorazole 3G. Parasitological cure was highest for the group on nimorazole 2GBD (100%) and lowest for the group on tinidazole (50%). Instruction to avoid sex during treatment were withheld from patients. This made it easier during the follow up to pick out and drop from the study those who had had sexual contact." ]

[ "8259762", "9854601", "1582098", "2977511", "7884329", "14339401", "19668674", "1192312", "4853949", "2019820", "2485986", "11528199" ]

[ "Hypnosis and self-hypnosis in the management of nocturnal enuresis: a comparative study with imipramine therapy.", "A controlled trial of desmopressin and behavioral therapy for nocturnal enuresis.", "Effect of diet treatment on enuresis in children with migraine or hyperkinetic behavior.", "Our experience with faradization of urinary bladder in enuretic children.", "Chiropractic management of primary nocturnal enuresis.", "ENURESIS--AN ETIOLOGIC AND THERAPEUTIC STUDY.", "Treatment of primary nocturnal enuresis: A randomized clinical trial comparing hypnotherapy and alarm therapy.", "Primary enuresis: relative success of three methods of treatment.", "Psychological changes associated with conditioning functional enuresis.", "Chiropractic care of children with nocturnal enuresis: a prospective outcome study.", "Treatment of nocturnal enuresis: a placebo-controlled trial with piracetam, diphenylhydantoin and psychotherapy.", "Prospective randomized trial using laser acupuncture versus desmopressin in the treatment of nocturnal enuresis." ]

[ "Various therapeutic modalities have been used for treating enuresis due to the lack of a single identifiable cause. We carried out a comparative study of imipramine and direct hypnotic suggestions with imagery used for the management of functional nocturnal enuresis. Enuretic children, ranging in age from 5 to 16 years, underwent 3 months of therapy with imipramine (N = 25) or hypnosis (N = 25). After termination of the active treatment, the hypnosis group continued practicing self-hypnosis daily during the follow-up period of another 6 months. Of the patients treated with imipramine, 76% had a positive response (all dry beds); for patients treated with hypnotic strategies, 72% responded positively. At the 9-month follow-up, 68% of patients in the hypnosis group maintained a positive response, whereas only 24% of the imipramine group did. Hypnosis and self-hypnosis strategies were found to be less effective in younger children (5-7 years old) compared to imipramine treatment. The treatment response was not related to the hypnotic responsivity of the patient in either group.", "The combination of desmopressin (DDAVP) and behavioral therapy for treatment of nocturnal enuresis was compared with use of each of these modes alone. We randomly assigned 226 enuretic children being treated in primary care clinics of a major medical center in the largest health maintenance organization in Israel into 3 groups: Group A) DDAVP plus behavioral therapy (double-blind); Group B) behavioral therapy plus placebo (double-blind); and Group C) DDAVP alone (open group). DDAVP (20 micrograms/naris) and placebo were administered by intranasal spray. Both pharmacologic and behavioral therapy were initiated after a 2-week observation period and continued for 8 weeks. All patients were followed for 2 months after completion of treatment. A significant reduction in the number of wet nights/week was registered for all 3 groups: 49% in Group A, 45% in Group B, and 19% in Group C. After controlling for confounding factors, no significant difference in effect was noted among the 3 types of treatment during the trial period. However, on follow-up the results for the DDAVP patients were significantly less stable compared with the other 2 groups (p = 0.015). Minor side effects were registered, but none of the participants withdrew from the trial. To our knowledge, this is the largest randomized trial of nocturnal enuresis conducted to date. Our findings suggest that simply discussing the problem with the patient and family leads to improvement, and that behavioral therapy is also beneficial. DDAVP can help, but the relapse rate on discontinuation is high.", "Twenty-one children with migraine and/or hyperkinetic behavior disorder which was successfully treated with an oligoantigenic (few-foods) diet also suffered from nocturnal and/or diurnal enuresis. On diet, the enuresis stopped in 12 of these children and improved in an additional four. Identification of provoking foods was by sequential reintroduction of the foods that were avoided on the oligoantigenic diet. In eight of the 12 children who recovered on the oligoantigenic diet and in the four who improved, reintroduction of one or more foods provoked a reproducible relapse of the enuresis. Nine children were subjected to a placebo-controlled, double-blind reintroduction of provoking foods. Six children relapsed during testing with incriminated foods; none reacted to placebo. Enuresis in food-induced migraine and/or behavior disorder seems to respond, in some patients, to avoidance of provoking foods.", "nan", "To evaluate chiropractic management of primary nocturnal enuresis in children.\n A controlled clinical trial for 10 wk preceded by and followed by a 2-wk nontreatment period.\n Chiropractic clinic of the Palmer Institute of Graduate Studies and Research.\n Forty-six nocturnal enuretic children (31 treatment and 15 control group), from a group of 57 children initially included in the study, participated in the trial.\n High velocity, short lever adjustments of the spine consistent with the Palmer Package Techniques; or a sham adjustment using an Activator at a nontension setting administered to the examiner's underlying contact point. Two 5th-year chiropractic students under the supervision of two clinic faculty performed the adjustments.\n Frequency of wet nights.\n The post-treatment mean wet night frequency of 7.6 nights/2 wk for the treatment group was significantly less than its baseline mean wet night frequency of 9.1 nights/2 wk (p = 0.05). For the control group, there was practically no change (12.1 to 12.2 nights/2 wk) in the mean wet night frequency from the baseline to the post-treatment. The mean pre- to post-treatment change in the wet night frequency for the treatment group compared with the control group did not reach statistical significance (p = 0.067). Twenty-five percent of the treatment-group children had 50% or more reduction in the wet night frequency from baseline to post-treatment while none among the control group had such reduction.\n Results of the present study strongly suggest the effectiveness of chiropractic treatment for primary nocturnal enuresis. A larger study of longer duration with a 6-month follow-up is therefore warranted.", "nan", "nan", "A total of 169 children with primary enuresis were treated by one of three methods--use of a special diet, imipramine, or a waking device (the Mozes detector). Of 64 who received the diet 1 (1.6%) was cured; of 62 who were treated with imipramine 13 (20.9%) were cured; and of 43 who used the detector 23 (53.5%) were cured. Results at follow-up remained substantially unchanged for cure. Improvement rate without cure during treatment was higher for the children treated with imipramine than for those treated with the detector, but at follow-up the reverse was true. Parents of children who received the special diet, because they were unimpressed by the rate of improvement, would not permit their children to continue this form of therapy for longer than 1 or 2 months.", "nan", "Functional nocturnal enuresis is a common problem which causes a great deal of stress to the suffering children and their families. Some chiropractors advocate chiropractic care as a mode of therapy for this complaint. One hundred and seventy-one enuretic children, aged 4 to 15, were treated with chiropractic adjustments, and their number of wet nights was monitored by their parents. The median number of wet nights per week was 7.0 at the onset of the study. After 2 wk without any therapy, the number of wet nights had decreased to 5.6 (p = .01) and by the end of the treatment this figure was 4.0 (p less than .0001). Following the course of treatment, 15.5% of subjects wet a maximum of 2 nights per fortnight, or, where data for the last 2 wk of therapy were unavailable, a maximum of 1 night/wk. This result is less favorable than the therapeutic success of other common types of therapy, which have reported \"cure\" rates well above 50%. The only variable which predicted treatment outcome was the initial estimate of bed-wetting; the more severe the condition at the onset, the less likely was the child to improve by the end of the study. In the absence of a control group there appears to be no validity in the claim that chiropractic is a treatment of choice for functional nocturnal enuresis.", "The study population consisted of 100 children with nocturnal enuresis (NE) aged between six and 14 years, who had been randomly selected amongst the enuretic outpatients at the Ankara S.S.K. Children's Hospital. A placebo-controlled evaluation of piracetam, diphenylhydantoin and psychotherapy was carried out. At the end of the eighth week of the study, it was discovered that the therapeutic effects observed in the patients administered piracetam did not differ from those given the placebo. Therefore, we recommend that psychotherapy in association with a placebo be the first step in the treatment of NE children.", "Several treatment modalities for children suffering from monosymptomatic nocturnal enuresis are available, but desmopressin is a well-established option. On the other hand, alternative nonpharmacological therapies such as laser acupuncture are more frequently requested by the parents. To our knowledge, there is no prospective randomized trial which evaluated the efficacy of such an alternative approach in comparison with the widespread use of desmopressin.\n Forty children aged over 5 years presenting with primary nocturnal enuresis underwent a previous evaluation of their voiding function to assure normal voiding patterns and a high nighttime urine production. Then the children were randomized into two groups: group A children were treated with desmopressin alone, and group B children underwent laser acupuncture. All children were investigated after a minimum follow-up period of 6 month to evaluate the duration of the response.\n The children of both groups had an initial mean frequency of 5.5 wet nights per week. After a minimum follow-up period of 6 months reevaluation revealed a complete success rate of 75% in the desmopressin-treated group. Additional 10% of the children had a reduction of their wet nights of more than 50%. On the other hand, 6 months after laser acupuncture, 65% of the randomized children were completely dry. Another 10% had a reduction of the enuresis frequency of more than 50% per week. 20% of the children in the desmopressin-treated group did not respond at all as compared with 15% in the acupuncture-treated group. Statistical evaluation revealed no significant differences among the response rates in both groups.\n Im comparison with pharmacological therapy using desmopressin, our study shows that laser acupuncture should be taken into account as an alternative, noninvasive, painless, cost-effective, and short-term therapy for children with primary nocturnal enuresis in case of a normal bladder function and high nighttime urine production. Success rates indicated no statistically significant differences between the well-established desmopressin therapy and the alternative laser acupuncture." ]

[ "8359791", "11994337", "2681348" ]

[ "Psychological aspects of the Canadian randomized controlled trial of human growth hormone and low-dose ethinyl oestradiol in children with Turner syndrome. The Canadian Growth Hormone Advisory Group.", "Growth hormone and low dose estrogen in Turner syndrome: results of a United States multi-center trial to near-final height.", "Acceleration of growth in Turner syndrome patients treated with growth hormone: summary of three-year results." ]

[ "Preliminary results are presented after 2 years of the Canadian long-term multicentre study on the impact of hormone therapy on the final height, sexual development and psychological status of girls with Turner syndrome. Girls entering the study were randomized either to be treated with recombinant human growth hormone or to act as controls. Both groups received oestrogen replacement therapy in the same dose and format at the age of 13 years. However, for the purposes of the psychological study at this time, children receiving oestrogen were excluded from analysis. Girls treated with GH for a period of 2 years showed a significant increase in growth rate, which declined with continued treatment, while the growth rate in the control group remained constant throughout. There was a correlation between the higher growth rate and the girls' perceptions of themselves as more intelligent, more attractive, having more friends, greater popularity and experiencing less teasing than the untreated group. Growth rate was not correlated with family or school functioning.", "A cardinal clinical feature of Turner syndrome (TS) is linear growth failure resulting in extreme short stature: the median adult height of untreated women with TS is 143 cm, 20 cm (8 in.) below that of the general female population. In the largest multicenter, randomized, long-term, dose-response study conducted in the United States, 232 subjects with TS received either 0.27 or 0.36 mg/kg.wk of recombinant human GH with either low dose ethinyl E2 or oral placebo. The study was placebo-controlled for both GH and estrogen for the first 18 months and remained placebo-controlled for estrogen for its duration. The near-final height of the 99 subjects whose bone age was at least 14 yr was 148.7 +/- 6.1 cm after 5.5 +/- 1.8 yr of GH started at a mean age of 10.9 +/- 2.3 yr; this represents an average increase of 1.3 +/- 0.6 SD scores from baseline (TS standard). Height was greater than 152.4 cm (60 in.) in 29% of subjects compared with the expected 5% of untreated patients. Mean near-final heights of subjects who received the lower GH dose, with or without estrogen, were 145.1 +/- 5.4 and 149.9 +/- 6.0 cm, respectively; those who received the higher GH dose with or without estrogen achieved mean near-final heights of 149.1 +/- 6.0 and 150.4 +/- 6.0 cm, respectively. Factors that most impacted outcome were younger age, lower bone age/chronological age ratio, lower body weight, and greater height SD score at study entry. This study demonstrates significant GH-induced improvement in height SD score, with correction of height to within the normal channels for a significant number of patients, and provides evidence of a GH dose-response effect. These data also indicate that early administration of estrogen, even at relatively low doses, does not improve gain in near-final height in patients with TS.", "In 1983, a multicenter, collaborative, prospective study was begun to investigate the efficacy of human growth hormone (hGH), alone and in combination with oxandrolone, in girls with Turner syndrome. While subjects in the control group grew 3.8 cm/yr (-0.1 SD for untreated Turner patients), subjects receiving hGH alone grew 6.6, 5.4 and 4.6 cm/yr in years 1-3, respectively (+3.1, +2.0, +1.4 SD). Subjects in the combination therapy group grew 9.8, 7.4 and 6.1 cm/yr (+6.6, +4.3, +3.0 SD). Turner subjects in both treatment groups showed increased in Bayley-Pinneau predicted adult heights and in Turner projected adult heights." ]

[ "10485722", "9197872" ]

[ "Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial.", "Antioxidants in the treatment of severe pre-eclampsia: an explanatory randomised controlled trial." ]

[ "Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia.\n 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study.\n Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002).\n Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.", "To determine whether antioxidant therapy alters the disease process in severe early onset pre-eclampsia, in support of the hypothesis that increased lipid peroxides and reactive oxygen species production-play an important role in the pathogenesis of the disease.\n Randomised, double-blind, placebo controlled trial.\n Two tertiary care, referral hospitals in Johannesburg, South Africa.\n Women with severe pre-eclampsia diagnosed between 24 and 32 weeks of gestation.\n Combined antioxidant treatment with vitamin E (800 IU/day), vitamin C (1000 mg/day), and allopurinol (200 mg/day).\n Primary outcomes: 1. prolongation of pregnancy and 2, biochemical assessment of lipid peroxides and antioxidants. Secondary outcomes: data on maternal complications, side effects of treatment, infant outcomes and regular assessment of haematologic and renal parameters.\n The proportion of women delivered within 14 days in the antioxidant group was 52% (14/27) compared with 76% (22/29) in the placebo group (relative risk 0.68, 95% confidence interval 0.45-1.04). One woman in each group had eclampsia. Eleven women (42%) in the antioxidant and 16 (59%) in the placebo group required two antihypertensives for blood pressure control. Trial medications were well tolerated with few side effects. Lipid peroxide levels were not significantly altered in the antioxidant and placebo groups. Serum uric acid levels decreased and vitamin E levels increased significantly.\n The results of this explanatory randomised trial do not encourage the routine use of antioxidants against pre-eclampsia. However, further research with modified strategies such as earlier initiation of therapy or different combinations seem worthwhile." ]

[ "9447502", "1642129", "17846102", "1705151", "9169246", "11087767", "11431060" ]

[ "Pilot study of haloperidol, fluoxetine, and placebo for agitation in Alzheimer's disease.", "Fluvoxamine in the treatment of demented elderly patients: a double-blind, placebo-controlled study.", "A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia.", "The clinical efficacy of citalopram in treatment of emotional disturbances in dementia disorders. A Nordic multicentre study.", "A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia.", "Treatment of agitation in AD: a randomized, placebo-controlled clinical trial.", "Sertraline versus small doses of haloperidol in the treatment of agitated behavior in patients with dementia." ]

[ "This pilot study compared haloperidol, fluoxetine, and placebo for reduction of agitation in 15 outpatients with AD. The two drugs were no more effective than placebo at reducing agitation in these subjects; however, both drugs produced more toxicity than did placebo.", "The efficacy of fluvoxamine on cognitive functioning and behavioral changes was evaluated in a double-blind, placebo-controlled study of 46 elderly demented patients. The patients had a DSM-III diagnosis of primary degenerative dementia or multi-infarct dementia and were aged greater than or equal to 65 years. Twenty-two patients were given 150 mg fluvoxamine per day and 24 received placebo tablets; 14 and 15 patients, respectively, completed 6 weeks of treatment. Within treatments, there were no significant changes in median scores on neuropsychological tests (picture recall and recognition, trail making and finger tapping) or the GBS scale scores (degrees of dementia) or GBS subscale score (clinical profiles, including symptoms common in dementia, motor, emotional and intellectual functioning). Between treatments, the median changes in psychometric test scores did not differ significantly. However, within and between treatments, there were trends favoring fluvoxamine on symptoms common in dementia (confusion, irritability, anxiety, fear-panic, mood level and restlessness). In conclusion, the study does not support the hypothesis that fluvoxamine improves cognitive functioning or behavioral changes in elderly dementia patients.", "To compare citalopram and risperidone for the treatment of psychotic symptoms and agitation associated with dementia, with a priori hypotheses that risperidone would be more efficacious for psychosis and citalopram for agitation.\n A 12-week randomized, controlled trial in nondepressed patients with dementia hospitalized because of behavioral symptoms (N = 103) was conducted at the University of Pittsburgh Medical Center. Participants were consecutively recruited on an inpatient unit if they had at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions). Once they improved sufficiently, they were discharged to nursing homes, personal care homes, or residential homes for continued treatment. Planned pre-post and mixed model analyses of the main outcome measures of Neurobehavioral Rating Scale and Side Effect Rating Scale at baseline and at weekly/biweekly intervals were conducted.\n Completion rates did not differ for citalopram and risperidone (overall completion rate: 44%). Agitation symptoms (aggression, agitation, or hostility) and psychotic symptoms (suspiciousness, hallucinations, or delusions) decreased in both treatment groups but the improvement did not differ significantly between the two groups. There was a significant increase in side effect burden with risperidone but not with citalopram such that the two groups differed significantly.\n No statistical difference was found in the efficacy of citalopram and risperidone for the treatment of either agitation or psychotic symptoms in patients with dementia. These findings need to be replicated before citalopram or other serotonergic antidepressants can be recommended as alternatives to antipsychotics for the treatment of agitation or psychotic symptoms associated with dementia.", "In this multicenter study, the clinical efficacy of citalopram was investigated in 98 patients with moderate AD/SDAT or VD using a combined double-blind and open technique with placebo and citalopram. Analyses were made for each diagnosis after four weeks of double-blind treatment. Patients with AD/SDAT treated with citalopram showed a significant improvement in emotional bluntness, confusion, irritability, anxiety, fear/panic, depressed mood and restlessness. Those improvements were not found after treatment with placebo. There were no significant improvements in patients with VD. No improvements were recorded in motor or cognitive impairment. Citalopram provoked few and comparatively mild side-effects. None of the changes observed during the double-blind withdrawal period were identified as withdrawal symptoms or rebound phenomena.", "The authors compared the efficacy and side effects of trazodone and haloperidol for treating agitated behaviors associated with dementia. Twenty-eight elderly patients with dementia and agitated behaviors were randomly assigned to double-blind treatment with either trazodone (50-250 mg/day) or haloperidol (1-5 mg/day) for 9 weeks. There was no significant difference in improvement between the medication groups. Adverse effects, however, were more common in the group treated with haloperidol. Improvement in individual areas suggested that repetitive, verbally aggressive, and oppositional behaviors responded preferentially to trazodone, whereas symptoms of excessive motor activity and unwarranted accusations responded preferentially to haloperidol. These results indicate that moderate doses of trazodone and haloperidol are equally effective for treatment of overall agitated behaviors in patients with dementia, but specific symptoms may respond preferentially to a particular agent.", "Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs.\n To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients.\n A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden.\n Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments.\n Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.", "nan" ]

[ "9189040", "11843764", "6221247" ]

[ "Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Myasthenia Gravis Clinical Study Group.", "Immunoglobulin treatment versus plasma exchange in patients with chronic moderate to severe myasthenia gravis.", "[Long-term effects of plasma exchange in myasthenia. Results of a randomized study]." ]

[ "We have conducted a trial to randomly assess the efficacy and tolerance of intravenous immunoglobulin (i.v.Ig) or plasma exchange (PE) in myasthenia gravis (MG) exacerbation and to compare two doses of i.v.Ig. Eighty-seven patients with MG exacerbation were randomized to receive either three PE (n = 41), or i.v.Ig (n = 46) 0.4 gm/kg daily further allocated to 3 (n = 23) or 5 days (n = 23). The main end point was the variation of a myasthenic muscular score (MSS) between randomization and day 15. The MSS variation was similar in both groups (median value, +18 in the PE group and +15.5 in the i.v.Ig group, p = 0.65). Similar efficacy, although slightly reduced in the 5-day group was observed with both i.v.Ig schedules. The tolerance of i.v.Ig was better than that of PE with a total of 14 side effects observed in 9 patients, 8 in the PE group and 1 in the i.v.Ig group (p = 0.01). Although our trial failed to show a pronounced difference in the efficacy of both treatments, it exhibited a very limited risk for i.v.Ig. i.v.Ig is an alternative for the treatment of myasthenic crisis. The small sample sizes in our trial, however, could explain why a difference in efficacy was not observed. Further studies are needed to compare PE with i.v.Ig and to determine the optimal dosage of i.v.Ig.", "The purpose of this study was to compare the efficacy of high-dose intravenous immunoglobulin (IVIG) treatment with plasma exchange in patients suffering from moderate to severe myasthenia gravis (MG) in a stable phase. There are no controlled studies comparing IVIG with plasma exchange in patients who despite immunosuppressive treatment have persistent incapacitating MG symptoms. This was a controlled crossover study. Twelve patients with generalized moderate to severe MG on immunosuppressive treatment for at least 12 months were included. The patients were evaluated clinically using a quantified MG clinical score (QMGS) before and at follow-up visits after each treatment. One week after the treatments, the patients who received plasma exchange treatment showed a significant improvement in QMGS compared to baseline but although some improvement was seen after IVIG this did not reach statistical significance. Four weeks after both plasma exchange and IVIG treatments, there was a significant improvement in QMGS compared to baseline. One week and 4 weeks after treatment, no significant difference between the 2 treatments was found. Both treatments have a clinically significant effect 4 weeks out in patients with chronic MG, but the improvement has a more rapid onset after plasma exchange than after IVIG.", "A randomized study was carried out in 14 myasthenia patients to compare the long-term effects of two therapeutic regimens. Group I patients received prednisone 1 mg/kg/24 h for one month, then in decreasing dosage; in case of failure at the end of the first month, cyclophosphamide 2 mg/kg/24 h was added to the prednisone treatment. Group II patients received the same treatment associated with 3 plasma exchanges over a 10-day period; these were continued, if required, at the rate of once a week. The minimum follow up was one year. The results (greater improvement in muscular strength and vital capacity) were better after one month in group I and thereafter similar in both groups. However, the mean daily dose of prednisone was higher in Group I. The number of exacerbations of myasthenia was greater in group II (11 versus 2 in group I over a 24-months period). The mean fall in anti-R Ach ab was about the same in both groups. This study confirms the rapid effectiveness of plasma exchanges and their value in severe myasthenia. The higher incidence of exacerbations in Group II was probably due to a rebound phenomenon and points to the need for combined immuno-suppressive treatment." ]

[ "16820547", "14519177", "15514412", "17577801", "16246996", "18441375", "17290726", "18418793", "11560455", "15876899", "17632223", "18096137", "17846399", "11377644", "9707377", "17984409", "10053177", "15317642", "15052977", "16908788", "16517193", "17889314", "12171809", "12859700", "10707439", "14982688", "16366758", "12547469", "12079730", "14581254", "11694208", "12359680", "12132977", "17624979", "12714026", "15899687", "15364675", "15301658", "11199956", "17763111", "17558827", "15534159", "9337378", "7586937", "15479310", "14749158", "12610193", "12182272", "16820546", "9778204", "19395688", "17295567", "11068974", "17530112", "16649873", "15764422", "15681499", "12365880", "17145253" ]

[ "Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.", "A randomized controlled trial of oral selegiline plus nicotine skin patch compared with placebo plus nicotine skin patch for smoking cessation.", "Extended nortriptyline and psychological treatment for cigarette smoking.", "Bupropion and cognitive-behavioral treatment for depression in smoking cessation.", "Efficacy of bupropion and nortriptyline for smoking cessation among people at risk for or with chronic obstructive pulmonary disease.", "Nortriptyline plus nicotine replacement versus placebo plus nicotine replacement for smoking cessation: pragmatic randomised controlled trial.", "Randomized comparison of a nicotine inhaler and bupropion for smoking cessation and relapse prevention.", "A randomized controlled clinical trial of bupropion SR and individual smoking cessation counseling.", "Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. a randomized, controlled trial.", "A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia.", "A 12-week double-blind, placebo-controlled study of bupropion sr added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia.", "A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia.", "A double-blind, placebo-controlled, randomized trial of bupropion for smoking cessation in primary care.", "Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial.", "Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking.", "Randomized, double-blind, placebo-controlled trial of 2 dosages of sustained-release bupropion for adolescent smoking cessation.", "A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.", "Efficacy of bupropion and predictors of successful outcome in a sample of French smokers: a randomized placebo-controlled trial.", "[Effect of treatment for nicotine dependence in patients with COPD].", "Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up.", "A controlled trial of nortriptyline, sustained-release bupropion and placebo for smoking cessation: preliminary results.", "Bupropion and nicotine patch as smoking cessation aids in alcoholics.", "Stopping smoking: a prospective, randomized, double-blind study comparing nortriptyline to placebo.", "A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation.", "The effects of fluoxetine combined with nicotine inhalers in smoking cessation--a randomized trial.", "A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees.", "Combined effects of venlafaxine, nicotine replacement, and brief counseling on smoking cessation.", "A preliminary placebo-controlled trial of selegiline hydrochloride for smoking cessation.", "A placebo controlled trial of bupropion for smoking cessation in schizophrenia.", "Effectiveness of bupropion sustained release for smoking cessation in a health care setting: a randomized trial.", "A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia.", "A randomized trial of sertraline as a cessation aid for smokers with a history of major depression.", "Sustained-release bupropion for smoking cessation in African Americans: a randomized controlled trial.", "A randomized trial of bupropion and/or nicotine gum as maintenance treatment for preventing smoking relapse.", "Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study.", "Bupropion SR vs placebo for smoking cessation in health care professionals.", "Bupropion for smoking cessation: a randomized trial.", "Randomized clinical trial of the efficacy of bupropion combined with nicotine patch in the treatment of adolescent smokers.", "A preliminary study of bupropion sustained-release for smoking cessation in patients with chronic posttraumatic stress disorder.", "Efficacy of bupropion alone and in combination with nicotine gum.", "Bupropion and cognitive-behavioral therapy for smoking cessation in women.", "A randomized trial of nortriptyline combined with transdermal nicotine for smoking cessation.", "A comparison of sustained-release bupropion and placebo for smoking cessation.", "A reversible monoamine oxidase A inhibitor (moclobemide) facilitates smoking cessation and abstinence in heavy, dependent smokers.", "Effectiveness of bupropion as an aid to stopping smoking before elective surgery: a randomised controlled trial.", "Effects of sustained-release bupropion among persons interested in reducing but not quitting smoking.", "Nicotine patch therapy based on smoking rate followed by bupropion for prevention of relapse to smoking.", "Multicenter trial of fluoxetine as an adjunct to behavioral smoking cessation treatment.", "Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.", "A randomized trial of nortriptyline for smoking cessation.", "Sustained-release bupropion for hospital-based smoking cessation: a randomized trial.", "Fluoxetine, smoking, and history of major depression: A randomized controlled trial.", "Nicotine patch and paroxetine for smoking cessation.", "A randomized trial of smoking cessation. Medication versus motivation.", "Extended treatment with bupropion SR for cigarette smoking cessation.", "Double-blind placebo-controlled trial of fluoxetine in smoking cessation treatment including nicotine patch and cognitive-behavioral group therapy.", "Efficacy of bupropion in the indigenous Maori population in New Zealand.", "Psychological intervention and antidepressant treatment in smoking cessation.", "Bupropion for smokers hospitalized with acute cardiovascular disease." ]

[ "Varenicline, a partial agonist at the alpha4beta2 nicotinic acetylcholine receptor, has the potential to aid smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine.\n To determine the efficacy and safety of varenicline for smoking cessation compared with placebo or sustained-release bupropion (bupropion SR).\n A randomized, double-blind, placebo-controlled trial conducted between June 2003 and March 2005 at 14 research centers with a 12-week treatment period and follow-up of smoking status to week 52. Of 1413 adult smokers who volunteered for the study, 1027 were enrolled; 65% of randomized participants completed the study.\n Varenicline titrated to 1 mg twice daily (n = 344) or bupropion SR titrated to 150 mg twice daily (n = 342) or placebo (n = 341) for 12 weeks, plus weekly brief smoking cessation counseling.\n Continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9-12; primary end point) and through the follow-up period (weeks 9-24 and 9-52).\n During the last 4 weeks of treatment (weeks 9-12), 43.9% of participants in the varenicline group were continuously abstinent from smoking compared with 17.6% in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.69-5.50; P<.001) and 29.8% in the bupropion SR group (OR, 1.90; 95% CI, 1.38-2.62; P<.001). For weeks 9 through 24, 29.7% of participants in the varenicline group were continuously abstinent compared with 13.2% in the placebo group (OR, 2.83; 95% CI, 1.91-4.19; P<.001) and 20.2% in the bupropion group (OR, 1.69; 95% CI, 1.19-2.42; P = .003). For weeks 9 through 52, 23% of participants in the varenicline group were continuously abstinent compared with 10.3% in the placebo group (OR, 2.66; 95% CI, 1.72-4.11; P<.001) and 14.6% in the bupropion SR group (OR, 1.77; 95% CI, 1.19-2.63; P = .004). Treatment was discontinued due to adverse events by 10.5% of participants in the varenicline group, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common adverse event with varenicline was nausea, which occurred in 101 participants (29.4%).\n Varenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy. Varenicline's short-term and long-term efficacy exceeded that of both placebo and bupropion SR.\n clinicaltrials.gov Identifier: NCT00143364.", "To compare the effect of oral selegiline plus nicotine patch with placebo plus nicotine patch on smoking cessation rates.\n Randomized double-blind placebo-controlled trial.\n Three community-based clinics.\n One hundred and nine male and female smokers aged 18-55 years, who smoked at least 15 cigarettes/day.\n Oral selegiline, 2.5 mg, or placebo twice/day initiated 1 week before the quit day, followed by 5 mg oral selegiline or placebo twice daily for 26 weeks, plus active nicotine skin patch to all participants for the first 8 weeks only. Measures of continuous abstinence rates up to 52 weeks, withdrawal symptoms, blood pressure and adverse events incidence.\n Twenty-five per cent (14 of 56) were continuously abstinent for 52 weeks in the selegiline plus nicotine group compared with 11% (6 of 53) in the placebo plus nicotine group (P = 0.08). Craving for cigarettes was lower in the selegiline plus nicotine group 4 weeks after quit day (P = 0.02).\n Adding selegiline to nicotine patch was associated with a doubling of the 52-week continuous abstinence rate, but this difference was not statistically significant. Selegiline significantly reduced craving for cigarettes and appeared to mitigate the need for nicotine replacement therapy. The results suggest that selegiline is a promising drug for future smoking cessation research.", "Accepted treatments for cigarette smoking rarely achieve abstinence rates of >35% at 1 year. Low rates may reflect failure to provide extended and multifocal treatment for this complex and chronic addiction. Using a chronic disease model of smoking, the authors undertook a study to determine the effects of long-term antidepressant and psychological treatment.\n One hundred sixty smokers of > or =10 cigarettes/day were randomly assigned to one of four treatment conditions in a two-by-two (nortriptyline versus placebo by brief versus extended treatment) design. All subjects received 8 weeks of a transdermal nicotine patch, five group counseling sessions, and active or placebo treatment. Interventions for subjects in brief treatment ended at this point. Subjects in extended treatment continued taking drug or placebo to week 52 and received an additional 9 monthly counseling sessions, with checkup telephone calls midway through each session. Subjects were assessed at baseline and weeks 12, 24, 36, and 52. The principal outcome variables were repeated abstinence at each assessment after the first over a 1-year period and a point prevalence of 7 days of abstinence.\n At week 52, point-prevalence abstinence rates with missing subjects imputed as smokers were 30% for placebo brief treatment, 42% for placebo extended treatment, 18% for active brief treatment, and 50% for active extended treatment. With missing subjects omitted, these rates were 32%, 57%, 21%, and 56%, respectively.\n Comprehensive extended treatments that combine drug and psychological interventions can produce consistent abstinence rates that are substantially higher than those in the literature.", "This study is a randomized, double-blind, placebo-controlled clinical trial examining the effects of an intensive cognitive-behavioral mood management treatment (CBTD) and of bupropion, both singularly and in combination, on smoking cessation in adult smokers. As an extension of our previous work, we planned to examine the synergistic effects of CBTD and bupropion on smoking cessation outcomes in general and among smokers with depression vulnerability factors. Participants were 524 smokers (47.5% female, M (age) = 44.27 years) who were randomized to one of four 12-week treatments: (a) standard, cognitive-behavioral smoking cessation treatment (ST) plus bupropion (BUP), (b) ST plus placebo (PLAC), (c) standard cessation treatment combined with cognitive-behavioral treatment for depression (CBTD) plus BUP, and (d) CBTD plus PLAC. Follow-up assessments were conducted 2, 6, and 12 months after treatment, and self-reported abstinence was verified biochemically. Consistent with previous studies, bupropion, in comparison with placebo, resulted in better smoking outcomes in both intensive group treatments. Adding CBTD to standard intensive group treatment did not result in improved smoking cessation outcomes. In addition, neither CBTD nor bupropion, either alone or in combination, was differentially effective for smokers with single-past-episode major depressive disorder (MDD), recurrent MDD, or elevated depressive symptoms. However, findings with regard to recurrent MDD and elevated depressive symptoms should be interpreted with caution given the low rate of recurrent MDD and the low level of depressive symptoms in our sample. An a priori test of treatment effects in smokers with these depression vulnerability factors is warranted in future clinical trials.", "The observations that smokers with chronic obstructive pulmonary disease (COPD) are at increased risk of depression and that nicotine may have antidepressant effects and regulate mood provide a rationale for the use of antidepressant drugs for smoking cessation in patients with COPD. No clinical trial has studied the efficacy of bupropion hydrochloride and nortriptyline hydrochloride for smoking cessation in this patient population, to our knowledge.\n In a placebo-controlled double-dummy randomized trial, 255 adults at risk for COPD or with COPD were prescribed sustained-release bupropion (bupropion SR) (150 mg twice daily) or nortriptyline (75 mg once daily) for 12 weeks. All patients received smoking cessation counseling. The main outcome measure was prolonged abstinence from smoking from week 4 to week 26 after the target quit date.\n The use of bupropion SR and nortriptyline resulted in higher prolonged abstinence rates compared with placebo, although only the difference between bupropion SR and placebo was statistically significant (differences with placebo, 13.1% [95% confidence interval, 1.2%-25.1%] for bupropion SR and 10.2% [95% confidence interval, -1.7% to 22.2%] for nortriptyline). In patients with COPD, bupropion SR and nortriptyline seem efficacious in achieving prolonged abstinence (differences with placebo, 18.9% [95% confidence interval, 3.6%-34.2%] for bupropion SR and 12.9% [95% confidence interval, -0.8% to 26.4%] for nortriptyline). In participants at risk for COPD, no statistically significant differences with placebo in prolonged abstinence rates were found.\n Bupropion SR treatment is an efficacious aid to smoking cessation in patients with COPD. Nortriptyline treatment seems to be a useful alternative.", "To test the efficacy of nortriptyline plus nicotine replacement therapy compared with placebo plus nicotine replacement therapy for smoking cessation.\n Pragmatic randomised controlled trial.\n National Health Service stop smoking service clinics.\n 901 people trying to stop smoking.\n Participants chose their nicotine replacement product, including combinations of nicotine replacement therapy, and received behavioural support. Nortriptyline was started one to two weeks before quit day, with the dose increased from 25 mg to 75 mg daily for eight weeks and reduced if not tolerated.\n Primary outcome was prolonged confirmed abstinence at six months. Secondary outcomes were prolonged abstinence at 12 months, drug use, severity of side effects, nicotine withdrawal symptoms, and urges to smoke.\n 72 of 445 (16%) people using nortriptyline and 55 of 456 (12%) using placebo achieved prolonged abstinence at six months (relative risk 1.34, 95% confidence interval 0.97 to 1.86). At 12 months the corresponding values were 49 (11%) for nortriptyline and 40 (9%) for placebo (1.26, 0.84 to 1.87). 337 (79%) people in the nortriptyline arm and 325 (75%) in the placebo arm were taking combination treatment on quit day, median 75 mg per day in both groups. More people in the nortriptyline arm than in the placebo arm took lower doses. The nortriptyline arm had noticeably higher severity ratings for dry mouth and constipation than the placebo arm, with slightly higher ratings for sweating and feeling shaky. Both groups had similar urges to smoke, but nortriptyline reduced depression and anxiety. Overall, withdrawal symptom scores did not differ.\n Nortriptyline and nicotine replacement therapy are both effective for smoking cessation but the effect of the combination is less than either alone and evidence is lacking that combination treatment is more effective than either alone. Trial registration Current Controlled Trials ISRCTN57852484.", "To compare the combination of a nicotine inhaler and bupropion to either treatment alone for initiating smoking abstinence and relapse prevention.\n Smokers were randomized to receive a nicotine inhaler, bupropion, or both for 3 months. At 3 months, smoking-abstinent study participants were randomized to their initial medications or placebo. Participants who were smoking at 3 months were randomized to an alternative treatment regimen or placebo. This study was conducted from July 2001 to January 2003.\n A total of 1700 smokers were randomized to treatment (phase 1) for 3 months. Among the 941 study participants eligible for randomization to the phase 2 trial, 837 continued in the study. For the phase 2 trial, 405 smoking-abstinent participants were randomized to relapse prevention for 9 additional months, and 432 smokers were randomized to re-treatment for an additional 3 months. At the end of the initial 3 months of treatment (phase 1), 82 (14%) of 566, 145 (26%) of 567, and 194 (34%) of 567 study participants receiving a nicotine inhaler, bupropion, or both, respectively, were abstinent from smoking. Of the 405 smoking-abstinent participants at the end of 3 months, the bupropion group had more smokers than the placebo group (mean No. of smokers, 1.5 vs 1.1; P < .001), and the nicotine inhaler group had higher smoking abstinence rates at 12 months than the placebo group. Those receiving combination therapy had reduced rates of relapse to smoking for the first 3 months of relapse prevention, but this difference disappeared after the initial 3 months. Of the 432 study participants who were smoking at the end of 3 months and who received an alternative treatment regimen, the 223 smokers initially assigned to a nicotine inhaler were more likely to stop smoking at 6 months if they were re-treated with bupropion instead of placebo (8 [7%] of 111 vs 0 [0%] of 112; P = .003), and the 209 smokers initially treated with bupropion and re-treated with a nicotine inhaler did not have significantly higher smoking abstinence rates (6 [6%] of 104 vs 3 [3%] of 105; P = -.50).\n Combined therapy with a nicotine inhaler and bupropion increased smoking abstinence rates. Continuation of the initial combination therapy does not appear to prevent relapse to smoking. Timing of re-treatment and alternative approaches to relapse prevention should be further examined.", "Efficacy of bupropion SR and individual counseling as smoking cessation treatments was assessed in a randomized, placebo-controlled clinical trial among adult daily smokers. Bupropion SR treatment and counseling were fully crossed in this factorial design so that the efficacy of each treatment and the combination could be estimated, relative to a placebo medication and assessment control condition. Intent-to-treat analyses indicated that bupropion SR increased abstinence rates at the end of treatment, relative to the placebo medication conditions, for both biochemically confirmed 7-day point-prevalence abstinence (OR = 1.97, 95% CI 1.04-3.72) and self-reported prolonged abstinence (OR = 2.90, 95% CI 1.66-5.06). Bupropion SR treatment also improved latency to lapse and relapse and improved the latency between lapse and relapse in survival analyses. Medication effects were more modest for both 12-month point-prevalence abstinence (OR = 1.47, 95% CI 0.74-2.92) and prolonged abstinence (OR = 1.34, 95% CI 0.66-2.72). Counseling was not associated with increases in the likelihood of abstinence at any time point (odds ratios ranged from 0.80 to 1.16 across abstinence outcomes in the full intent-to-treat sample). Counseling and medication did not significantly interact at any time point, and adding counseling did not improve end-of-treatment point-prevalence abstinence (OR = 1.17, 95% CI 0.68-2.03) or prolonged abstinence (OR = 1.26, 95% CI 0.75-2.12) substantially when offered in conjunction with active medication.", "Smoking relapse is common after successful pharmacologic treatment for smoking cessation. No previous studies have examined long-term drug therapy used expressly for prevention of smoking relapse.\n To evaluate the efficacy of bupropion to prevent smoking relapse.\n Randomized, placebo-controlled trial.\n 784 healthy community volunteers who were motivated to quit smoking and who smoked at least 15 cigarettes per day.\n The participants received open-label, sustained-release bupropion, 300 mg/d, for 7 weeks. Participants who were abstinent throughout week 7 of open-label treatment were randomly assigned to receive bupropion, 300 mg/d, or placebo for 45 weeks and were subsequently followed for an additional year after the conclusion of the medication phase. Participants were briefly counseled at all follow-up visits. At the end of open-label bupropion treatment, 461 of 784 participants (58.8%) were abstinent from smoking.\n Self-reported abstinence was confirmed by an expired air carbon monoxide concentration of 10 parts per million or less.\n The point prevalence of smoking abstinence was significantly higher in the bupropion group than in the placebo group at the end (week 52) of drug therapy (55.1% vs. 42.3%, respectively; P = 0.008) and at week 78 (47.7% vs. 37.7%; P = 0.034) but did not differ at the final (week 104) follow-up visit (41.6% vs. 40.0%). The median time to relapse was significantly greater for bupropion recipients than for placebo recipients (156 days vs. 65 days; P = 0.021). The continuous abstinence rate was higher in the bupropion group than in the placebo group at study week 24 (17 weeks after randomization) (52.3% vs. 42.3%; P = 0.037) but did not differ between groups after week 24. Weight gain was significantly less in the bupropion group than in the placebo group at study weeks 52 (3.8 kg vs. 5.6 kg; P = 0.002) and 104 (4.1 kg vs. 5.4 kg; P = 0.016).\n In persons who stopped smoking with 7 weeks of bupropion treatment, sustained-release bupropion for 12 months delayed smoking relapse and resulted in less weight gain.", "The objective of this study was to examine the efficacy of bupropion for smoking cessation in patients with schizophrenia. Adults with schizophrenia who smoked more than 10 cigarettes per day and wished to try to quit smoking were recruited from community mental health centers, enrolled in a 12-week group cognitive behavioral therapy intervention, and randomly assigned to receive either bupropion sustained-release 300 mg/d or identical placebo. Fifty-three adults, 25 on bupropion and 28 on placebo, were randomized, completed at least 1 postbaseline assessment and were included in the analysis. The primary outcome measures were 7-day point prevalence abstinence in the week after the quit date (week 4) and at the end of the intervention (week 12). Subjects in the bupropion group were significantly more likely to be abstinent for the week after the quit date (36% [9/25] vs. 7% [2/28], P = 0.016) and at end of the intervention (16% [4/25] vs. 0%, P = 0.043). Subjects in the bupropion group also had a higher rate of 4-week continuous abstinence (weeks 8-12) (16% [4/25] vs. 0%, P = 0.043) and a longer duration of abstinence (4.2 [3.2] weeks vs. 1.8 [0.96] weeks, t = 2.30, P = 0.037). The effect of bupropion did not persist after discontinuation of treatment. Subjects in the bupropion group had no worsening of clinical symptoms and had a trend toward improvement in depressive and negative symptoms. We conclude that bupropion does not worsen clinical symptoms of schizophrenia and is modestly effective for smoking cessation in patients with schizophrenia. The relapse rate is high after treatment discontinuation.", "The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy (NRT) and weekly group cognitive behavioral therapy (CBT) for smoking reduction or cessation in schizophrenia. Fifty-one adult smokers with schizophrenia were randomly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch, nicotine polacrilex gum, and CBT. The treatment goal was smoking cessation. The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50% to 100% smoking reduction at week 12. Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide (CO) and psychiatric symptoms. Subjects on bupropion + NRT had a greater rate of 50% to 100% smoking reduction at weeks 12 (60% vs. 31%; P = 0.036) and 24, a lower expired air CO in the treatment and follow-up periods, (F = 13.8; P < 0.001) and a greater continuous abstinence rate at week 8, before NRT taper, (52% vs. 19%; P = 0.014). However, relapse rates in subjects on bupropion + dual NRT were 31% during NRT taper (weeks 8-12) and 77% at the 12-month follow-up. Abstinence rates did not differ by treatment group at weeks 12 (36% vs. 19%), 24 (20% vs. 8%), or 52 (12% vs. 8%). Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment, study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention.", "Individuals with schizophrenia smoke at higher rates (58%-88%) than the general population (approximately 22%), and have difficulty quitting. We determined whether the combination of sustained-release (SR) bupropion (BUP) with the transdermal nicotine patch (TNP) was well-tolerated and superior to placebo (PLO)+TNP for smoking cessation in schizophrenia.\n A 10-week, double-blind, placebo-controlled trial of BUP (300 mg/day) in combination with TNP (21 mg/24h) for 58 outpatient smokers with schizophrenia was conducted. Primary outcome measures were continuous smoking abstinence in the last 4 weeks of the trial (Days 43-70) and 7-day point prevalence abstinence at 6 months post-target quit date (TQD) (week 26).\n Smokers assigned to the BUP+TNP group (n = 29) were more likely to achieve continuous smoking abstinence (8/29, 27.6%) than the PLO+TNP group (n = 29, 1/29, 3.4%) [Fisher's Exact Test, p < .05]; at 6-months post-TQD, 4/29 (13.8%) versus 0/29 (0.0%) achieved 7-day point prevalence smoking abstinence (p = .11). Neither bupropion SR nor smoking abstinence significantly altered the positive or negative symptoms of schizophrenia. The combination was well-tolerated in smokers with schizophrenia.\n Combination therapy with bupropion SR+TNP versus placebo+TNP is well-tolerated and significantly improved short-term smoking abstinence in smokers with schizophrenia.", "Studies undertaken in academic settings have shown that bupropion hydrochloride can double the odds of smoking cessation compared with placebo. To assess whether these results are applicable in primary care, we launched a double-blind, placebo-controlled, randomized trial to be conducted by general practitioners.\n We assigned 593 healthy smokers to receive bupropion hydrochloride, 150 mg twice a day, or placebo daily for 7 weeks (hereinafter, bupropion group [n = 400] and placebo group [n = 193], respectively). After the baseline visit, 4 clinical visits and 3 telephone calls were scheduled over the 1-year period. The primary end points were biochemically confirmed continuous abstinence at week 7 and at week 52.\n Seventy-one Italian general practitioners enrolled participants from April 2004 to May 2005. Of the bupropion group, 41.0% were continuously abstinent from week 4 to week 7 compared with 22.3% of the placebo group (multivariate odds ratio, 2.37; 95% confidence interval, 1.60-3.53). The continuous abstinence rates from week 4 to week 52 were 25% in the bupropion group and 14% in the placebo group (odds ratio, 2.11; 95% confidence interval, 1.32-3.39). The mean weight gain was similar in both groups and among long-term abstainers was 3 kg in women and 4 kg in men. More participants in the bupropion group experienced an adverse event than those in the placebo group, but the percentage who discontinued use of the study medication was similar.\n Bupropion more than doubled the odds of continuous abstinence from smoking. The adherence of general practitioners and participants to the protocol was excellent, making our findings robust and easy to generalize to the context of primary care.", "Tobacco smoking is associated with chronic obstructive pulmonary disease (COPD) in more than 80% of cases. Our aim was to investigate the effect of sustained-release bupropion (amfebutamone) (SR) in promoting abstinence from smoking in patients with COPD.\n In a double-blind, randomised, placebo-controlled trial 404 individuals with mild or moderate COPD who smoked 15 or more cigarettes per day, were assigned bupropion SR (150 mg twice daily) or placebo for 12 weeks. All patients received smoking cessation counselling. Study medication was taken for 1 week before patients attempted to stop smoking. The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of week 4 to the end of week 7. Participants were followed up at month 6. Analysis was by intention to treat.\n All patients were chronic smokers with a smoking history of about 51 pack-years. Continuous smoking abstinence rates from week 4 to 7 were significantly higher in participants receiving bupropion SR than in those receiving placebo (28% [57/204] vs 16% [32/200], p=0.003). Continuous abstinence rates from weeks 4 to 12 (18% [36/204] vs 10% [20/200]) and weeks 4 to 26 (16% [32/204] vs 9% [18/200]) were also higher in participants receiving bupropion SR than in those taking placebo (p<0.05). Furthermore, symptoms of tobacco craving and withdrawal were attenuated in those receiving bupropion SR. Seven individuals discontinued study medication because of adverse events.\n Bupropion SRis a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD.", "A history of major depressive disorder (MDD) predicts failure to quit smoking. We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD. The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence.\n This was a 2 (nortriptyline vs placebo) x 2 (cognitive-behavioral therapy vs control) x 2 (history of MDD vs no history) randomized trial. The participants were 199 cigarette smokers. The outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 38, and 64. Mood, withdrawal, and depression were measured at 3, 5, and 8 days after the smoking quit date.\n Nortriptyline produced higher abstinence rates than placebo, independent of depression history. Cognitive-behavioral therapy was more effective for participants with a history of depression. Nortriptyline alleviated a negative affect occurring after smoking cessation. Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessments for MDD history-negative smokers. There was also a sex-by-depression history interaction; MDD history-positive women were less likely to be abstinent than MDD history-negative women, but depression history did not predict abstinence for men.\n Nortriptyline is a promising adjunct for smoking cessation. Smokers with a history of depression are aided by more intensive psychosocial treatments. Mood and diagnosis interact to predict relapse. Increases in negative affect after quitting smoking are attenuated by nortriptyline.", "To assess the safety and efficacy of sustained-release bupropion hydrochloride for adolescent smoking cessation.\n Prospective, randomized, double-blind, placebo-controlled, dose-ranging trial.\n Metropolitan areas of Tucson and Phoenix, Arizona.\n Adolescents (N = 312) recruited through media and various community venues from March 1, 1999, through December 31, 2002, who were aged 14 to 17 years, smoked 6 or more cigarettes per day, had an exhaled carbon monoxide level of 10 ppm or greater, had at least 2 previous quit attempts, and had no other current major psychiatric diagnosis.\n Sustained-release bupropion hydrochloride, 150 mg/d (n = 105) or 300 mg/d (n = 104), or placebo (n = 103) for 6 weeks, plus weekly brief individual counseling. Subjects were followed up at 12 weeks (by telephone call) and 26 weeks.\n Confirmed 7-day point prevalence abstinence at 6 weeks and 30-day prolonged abstinence (carbon monoxide level < 10 ppm at each visit; urinary cotinine level < or = 50 microg/L at weeks 2 and 6).\n Cotinine-confirmed 7-day point prevalence abstinence rates at 6 weeks were as follows: placebo, 5.6%; 150 mg, 10.7%; and 300 mg, 14.5% (P = .03, 300 mg vs placebo). At 26 weeks, confirmed point prevalence abstinence rates were as follows: placebo, 10.3%; 150 mg, 3.1%; and 300 mg, 13.9% (P = .049). During treatment, confirmed point prevalence rates were significantly higher for 300 mg than placebo at every week except week 4.\n Sustained-release bupropion hydrochloride, 300 mg/d, plus brief counseling demonstrated short-term efficacy for adolescent smoking cessation. Abstinence rates were lower than those reported for adults, with rapid relapse after medication discontinuation.\n clinicaltrials.gov Identifier: NCT00344695.", "Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8.\n The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache.\n Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.", "Previous published studies assessed the efficacy of bupropion in smoking cessation only in North American populations of smokers. Results of therapeutic drug trials are not always directly applicable in other populations.\n To confirm the efficacy of bupropion in smoking cessation in European smokers.\n A multi-centre, randomized, double-blind placebo-controlled trial.\n Seventy-four smoking cessation out-patient clinics in France.\n The study included 509 smokers motivated to quit smoking. Intervention Subjects were randomized to either slow-release bupropion 150 mg b.i.d. (B) or to placebo (Pl) in a 2 : 1 ratio, treated for 7 weeks, and followed-up for 26 weeks.\n Main outcome measure: 6 months' point prevalence abstinence, determined by self-report and expired air carbon monoxide measurement. Secondary outcome measures: weeks 4-7 and weeks 4-26 continuous abstinence rates, craving, withdrawal symptoms, weight and cigarette consumption in smokers unable to quit. Adverse events were recorded systematically.\n Six months' point prevalence abstinence rates were 31% and 16%[odds ratio = 2.3, confidence interval (CI) 95%: 1.4-3.7] in the B and Pl groups, respectively. Continuous abstinence rates were 41% (B) and 21% (P) with OR = 2.5 (CI 95%: 1.6-3.9) for weeks 4-7, and 25% (B) and 13% (P) with OR = 2.2 (CI 95%: 1.3-3.6) for weeks 4-26, respectively. Craving decreased significantly more with B than with Pl during treatment period, but there was no difference for total withdrawal symptoms score. Abstinent subjects gained significantly less weight at week 7 with B than with Pl. Low level of nicotine dependence, high motivation, absence of smoking-related disease, long duration of previous quit attempts, male gender, low level of current alcohol problems and living as a couple were predictive of successful cessation. With the exception of marital status, no interaction was observed between any of these predictive factors and the efficacy of bupropion. More of those who continued smoking in the B group than the P group reduced their consumption by at least 50%.\n Sustained-release bupropion is efficacious as an aid to smoking cessation in European smokers. No outcome predictors were identified that might indicate that certain subgroups of smokers would benefit more than others from treatment with bupropion.", "Stopping smoking is the only known method to slow down the inevitable progression of COPD. Early detection of the disease in smokers at risk of COPD gives a unique opportunity to prevent the disease progression. The aim of the study was to evaluate the effects of smoking intervention in a group of subjects with newly diagnosed airflow limitation (AL). Of 558 current smokers participating in population spirometric screening for COPD combined with smoking cessation advice, 297 were diagnosed to have AL (FEV1/FVC < 0.7). After one year 193 presented for follow-up visit. Thirty subjects (10.1%) quit smoking. Remaining 163 smokers were invited to smokers' clinic. Attendees (n = 70), 40 males, and 30 females, mean age 56 years, were randomized at visit 1 to treatment with nicotine patch (n = 38) or bupropion SR (n = 32). Follow-up was scheduled at 2 weeks, at the end of treatment, 6 months and 12 months. After 12 months a phone call assessed the smoking status. Non smoking was validated with carbon monoxide measurements in exhaled air. Patients who did not attend the follow-up visits were considered smokers. The number of participants at follow-up decreased significantly: from 70 subjects at visit one to 57 after 2 weeks, 34 at end of treatment and 14 subjects at months. Almost all (n = 69) were reached at 12 month by the phone. The validated quit rate after 12 months was 18.5% (13/70), 8 in group treated with nicotine patch and 5 in the group treated with bupropion SR (NS). When total group of smokers with newly diagnosed COPD was considered 10% quit smoking as result of minimal intervention with another 4.5% after pharmacological treatment.", "Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control.\n A phase 2, multicenter, randomized, double-blind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n = 128), 1.0 mg once daily (n = 128), or 1.0 mg twice daily (n = 127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n = 128) for 7 weeks; or to placebo (n = 127) for 7 weeks.\n During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%; P<.001) and 1.0 mg once daily (37.3%; P<.001), than for placebo (17.1%). The bupropion rate was 33.3% (P = .002 vs placebo). The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group (14.4% vs 4.9%; P = .002). The bupropion rate was 6.3% (P = .60 vs placebo). Discontinuation owing to treatment-emergent adverse events was 15.9% for bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. No dose-related increases occurred in adverse events for varenicline.\n Varenicline tartrate demonstrated both short-term (1 mg twice daily and 1 mg once daily) and long-term efficacy (1 mg twice daily) vs placebo. Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation.", "Cognitive behavior therapy (CBT) constitutes the basis of smoking cessation programs. Quitting rates are usually increased by the concomitant use of CBT and pharmacotherapy. There are studies showing the efficacy of bupropion and nortriptyline compared to placebo, but there is just one published comparison between these drugs, unfortunately with low power to detect significant differences. This study was designed to compare the efficacy of bupropion, nortriptyline and placebo in a group of smokers who also received intensive counseling therapy. We conducted a double blind, double-dummy, placebo-controlled trial for smoking cessation that lasted 9 weeks. Patients were randomized to receive nortriptyline 75 mg/day (52 subjects), bupropion 300 mg/day (53 subjects) or placebo (51 subjects). All smokers also received the same intensive cognitive behavior therapy. The target day for quitting smoking was usually day 10. Intensive counseling was provided at baseline, weekly during treatment, and at 10, 13, 16, 20 and 26 weeks. Abstinence was defined as continuous when the subject was not smoking since the target-quitting day (self-report) and had an expired carbon monoxide concentration of 10 ppm or less.\n The sustained abstinence rates at 6 months were 21.6% in the placebo group, 30.8% in the nortriptyline group (p = 0.40), and 41.5% in the bupropion group (p = 0.05). The odds ratio was not statistically different for smokers using nortriptyline or bupropion (OR 1.60; 95% CI 0.66-3.86; p = 0.35). The most common adverse events were dry mouth and drowsiness in the nortriptyline group and dry mouth and insomnia in the bupropion group.\n Treatment with CBT + bupropion resulted in a better 6-month rate of smoking cessation compared to CBT+nortriptyline or CBT + placebo. Abstinence rate in the nortriptyline group was not statistically different from patients in the bupropion or placebo group.", "This is a double-blind placebo-controlled study of sustained-release bupropion as a smoking cessation aid in alcoholics undergoing treatment for their alcoholism. Participants (N=58) were enrolled within 1 week of entry into alcohol treatment from community and Veterans Affairs Substance Use Disorder programs. All participants received nicotine patch and were invited to attend a smoking cessation lecture and group. Cigarette smoking and alcohol outcomes were measured at 6 months. Bupropion when added to nicotine patch did not improve smoking outcomes. One third of participants on bupropion reported discontinuing the drug during weeks 1-4. Participants reported cigarette outcomes with nicotine patch that are similar to those seen in the general population. All study participants significantly reduced cigarette use. Comorbid affective disorder or antipersonality disorder did not affect outcomes. Alcohol outcomes were improved in those who discontinued cigarettes.", "The administration of antidepressant drugs was shown to positively affect the rate of smoking cessation. This study evaluates the efficacy of nortriptyline in an antismoking program.\n A possible randomized double-blind study that included 144 patients who were randomized to receive nortriptyline, 75 mg/d (68 patients), or placebo (76 patients), during 6 consecutive weeks. All patients attended behavioral group orientation for 5 weeks. The rate of success, complications, adherence to the regime, and factors of pretreatment prognosis were evaluated (multivariate analysis).\n The groups were balanced in relation to the characteristics of the patients on entering the study. Patients receiving nortriptyline showed significantly higher cessation rate (55.9%) compared to the group receiving placebo (23.3%; p < 0.001). In a univariate analysis on prognosis factors influencing the rate of cessation in our study, the Fagerström test results (p = 0.005) and nortriptyline (p < 0.001) were identified. Logistic regression showed that a Fagerström test score of < 7 (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.47 to 6.7; p = 0.003) and nortriptyline use (OR, 4.1; 95% CI, 2 to 8.3; p < 0.001) were independent factors impacting the rate of success for smoking cessation. No significant complications were observed in the nortriptyline group.\n This study showed that nortriptyline significantly increases the smoking cessation rate in chronic smokers, as compared to the placebo group, without any significant side effects.", "Bupropion sustained release (bupropion SR) has been shown to increase smoking cessation success rates in the US studies.\n To determine whether bupropion SR, in combination with counselling, is effective for smoking cessation in a multi-country study.\n This randomized, double-blind, placebo-controlled trial enrolled 707 smokers. A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo. A total of 11 clinic visits and 10 telephone contacts were scheduled, during the course of 1 year. Seven-week and 12-month abstinence rates were the study outcomes.\n Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo. The continuous abstinence rate from weeks 4 to 7 was 46% in the bupropion SR group compared with 23% in the placebo group [odds ratio (OR) = 2.82; 95% confidence interval (CI) 1.89-4.28; P < 0.001). At month 12, the continuous abstinence rates were 21% for the bupropion SR group and 11% for the placebo group (OR = 2.19; 95% CI 1.29-3.86, P = 0.002). For most nicotine-withdrawal symptoms small changes were measured. Adverse events were higher for the bupropion SR group compared with placebo (insomnia 24% vs. 15%; dry mouth 13% vs. 5%).\n Bupropion SR in combination with counselling increased the abstinence rate compared with placebo, and was well tolerated.", "Nicotine replacement therapy (NRT) is an established aid in stopping smoking, while the role of antidepressants remains uncertain. Antidepressants added to NRT might improve abstinence rates. Our aim was to determine the efficacy of nicotine inhaler and fluoxetine vs. nicotine inhaler and placebo in attempts to quit smoking.\n A randomized, double-blind, placebo-controlled trial.\n A smoker's cessation clinic.\n One hundred volunteers smoking 10 cigarettes/day or more.\n Subjects were instructed to start taking a daily dose of 10 mg of fluoxetine or placebo 16 days before stopping smoking, then 20 mg 10 days before quitting, continuing for up to at least 3 months. Subjects were instructed to use 6-12 units per day of nicotine inhalers after stopping smoking for up to 6 months.\n Continuous abstinence rates recorded at various time points up to 12 months from the quit date.\n The sustained abstinence rate for the inhaler-fluoxetine group was 54%, 40%, 29% and 21% after 1.5, 3, 6 and 12 months, respectively, compared to 48%, 40%, 32% and 23% for the inhaler-placebo group. The differences were not significant at any time point. Abstinence up to 3 months was more likely in older smokers, those with a lower Beck Depression Inventory Score (BDI), lower Fagerström Test of Nicotine Dependence (FTND) score and no history of alcoholism. Fluoxetine appeared to increase abstinence rates among high BDI smokers compared to high BDI smokers assigned placebo. Serum levels of nicotine during treatment in the inhaler-fluoxetine group were lower than in the inhaler-placebo group so that fluoxetine may have reduced inhaler use through a common site of action.\n We found no evidence that fluoxetine treatment when used as an adjunct to NRT in unselected smokers is effective, but there may be an advantage to using it in depressed smokers.", "Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release (Zyban) compared with placebo as an aid to smoking cessation in health care workers. A total of 336 hospital employees who smoked at least 10 cigarettes daily were randomized (2:1) to 7 weeks of treatment with bupropion (n=222) or placebo (n=114). All participants were motivated to quit smoking and received behavioral counseling. Continuous smoking abstinence during weeks 4-7 was the primary endpoint, and long-term smoking abstinence was among the secondary endpoints. Of the original participants, 212 completed the 6-month trial. Continuous smoking abstinence at week 7 was achieved by 43% in the bupropion group and 18% in the placebo group, p<.001. After 26 weeks, 18% and 7%, respectively, were continuously abstinent, p=.008. Side-effects were frequent but simple and reversible in both groups, and generally consistent with the findings of previous studies. Dizziness, insomnia, and pruritus appeared more frequently in the bupropion group than in the placebo group. Bupropion was effective as an aid to smoking cessation in a broad group of hospital employees in Denmark.", "In this study, 147 smokers were randomly assigned to receive either venlafaxine or placebo in conjunction with behavioral counseling (9 weekly sessions) and transdermal nicotine replacement therapy (22 mg/day). Patients began medication 2 weeks before quitting and continued for 18 weeks after quitting, with the daily dose titrated from 150 to 225 mg. in response to symptoms of negative affect and relapse. The results showed no main effect of treatment on abstinence. Post hoc analysis revealed that both at the end of treatment and at the 1-year follow-up smokers consuming less than a pack of cigarettes a day benefited from the addition of venlafaxine to the treatment regimen. Venlafaxine also reduced negative affect for all smokers for up to 6 weeks postcessation. The findings suggest that venlafaxine could have some role to play in the treatment of lighter smokers, in addition to the expected benefits of nicotine replacement therapy and behavioral counseling.\n Copyright 2005 APA, all rights reserved.", "Since dopaminergic mechanisms appear to be involved in nicotine dependence, we studied the safety and efficacy of the monoamine oxidase B inhibitor selegiline hydrochloride compared with placebo for smoking cessation in nicotine-dependent cigarette smokers.\n Forty subjects with DSM-IV nicotine dependence were randomized to: 1) selegiline hydrochloride (5 mg p.o. twice daily) or 2) placebo in an 8-week trial. Outcome measures included smoking cessation rates, treatment retention, and medication side effects.\n Selegiline hydrochloride increased trial end point (week 8) 7-day point prevalence smoking cessation rates (selegiline hydrochloride, 9/20 [45.0%]; placebo, 3/20 [15.0%], odds ratio = 4.64, 95% CI, 1.02-21.00, p <.05), and smoking cessation rates during the last 4 weeks of the trial (selegiline hydrochloride, 6/20 [30.0%]; placebo, 1/20 [5.0%], odds ratio = 8.14, 95% CI, 0.88-75.48, p =.07) in comparison with placebo. Six-month follow-up 7-day point prevalence smoking cessation rates were reduced compared with trial end point (selegiline hydrochloride, 4/20 [20.0%]; placebo, 1/20 [5.0%], odds ratio = 4.75, 95% CI, 0.48-46.91, p =.18). Treatment retention was similar between drug and placebo groups (p =.13), and selegiline hydrochloride was well tolerated in cigarette smokers.\n This preliminary study suggests that selegiline (10 mg/day) is safe for use and enhances smoking cessation rates compared with placebo in nicotine-dependent cigarette smokers.", "Schizophrenic patients have high rates of cigarette smoking compared with the general population. We compared sustained-release (SR) bupropion with placebo for smoking cessation in patients with schizophrenic disorders. We also examined how antipsychotic class predicts smoking cessation outcomes with bupropion.\n Thirty-two subjects meeting DSM-IV criteria for schizophrenia or schizoaffective disorder and nicotine dependence were randomized to bupropion SR (BUP, 300 mg/day) or placebo (PLA). Outcomes included treatment retention, smoking abstinence rates, expired breath carbon monoxide (CO) levels, psychotic symptoms, and medication side effects.\n Bupropion significantly increased trial endpoint 7-day point prevalence smoking abstinence rates compared with placebo [BUP, 8/16 (50.0%), PLA, 2/16 (12.5%); chi(2) = 5.24, df = 1, p <.05], and reduced CO levels during the trial [Medication x Time interaction; Z = 3.09, p <.01]. Positive schizophrenia symptoms were not altered by BUP, but negative symptoms were significantly reduced. Atypical antipsychotic drug treatment enhanced smoking cessation responses to BUP. Major side effects were dry mouth, gastrointestinal symptoms, headache, and insomnia.\n Our results suggest that 1) BUP enhances smoking abstinence rates compared with PLA in nicotine-dependent schizophrenic smokers; 2) BUP is well-tolerated and safe for use in these patients; and 3) atypical antipsychotics may enhance smoking cessation outcomes with BUP.", "The efficacy of bupropion hydrochloride sustained release (SR) (Zyban) for smoking cessation has been evaluated in clinical trials that included frequent in-person behavioral counseling, but not in actual practice settings.\n To determine the differential effectiveness of 2 doses of bupropion SR in combination with behavioral interventions of minimal to moderate intensity in an actual practice setting.\n Open-label randomized trial, with 1 year of follow-up.\n A large health system (Group Health Cooperative) based in Seattle.\n Adult smokers (N = 1524) interested in quitting smoking.\n Participants were randomly assigned to receive 1 of 4 combinations of bupropion SR (150 or 300 mg) and behavioral counseling (minimal or moderate intensity).\n The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 3 and 12 months following the target quit date. Secondary outcomes included adverse and abstinence effects reported since beginning treatment with bupropion SR.\n At 3 months, a significantly higher rate of nonsmoking was observed among those receiving the larger bupropion SR dose (P=.005). At 12 months, moderate intensity counseling was associated significantly with a higher rate of nonsmoking (P=.001). At 3 months, the higher dose was associated with a significantly increased frequency of self-reported symptoms such as difficulty sleeping (P=.02), difficulty concentrating (P=.02), shakiness/tremor (P=.002), and gastrointestinal problems (P=.005)and a decreased frequency of reported desire to smoke (P=.001).\n In this actual practice setting, the combination of bupropion SR and minimal or moderate counseling was associated with 1-year quit rates of 23.6% to 33.2%. This suggests that existing health care systems can substantially decrease tobacco use rates among their enrollees if they provide these modest interventions.", "The purpose of this study was to investigate the effect of adding sustained-release (SR) bupropion to cognitive behavioral therapy (CBT) on smoking behavior and stability of psychiatric symptoms in patients with schizophrenia. We conducted a 3-month, double-blind, placebo-controlled trial of bupropion SR, 150 mg/day, added to a concurrent CBT program with 3-month follow-up in 19 stable outpatients with schizophrenia who wanted to quit smoking. Eighteen subjects completed the trial. Bupropion treatment was associated with significantly greater reduction in smoking, as measured by self-report verified by expired-air carbon monoxide (6/9 subjects, 66%), than placebo (1/9 subjects, 11%) during the 3-month active treatment period and the 3-month follow-up period. One subject in the bupropion group (11%) and no subjects in the placebo group achieved sustained tobacco abstinence for the 6-month trial. Bupropion treatment was associated with improvement in negative symptoms and greater stability of psychotic and depressive symptoms, compared with placebo, during the quit attempt. Subjects in the bupropion group experienced significant weight loss, compared with those on placebo during the smoking cessation attempt. These data suggest that bupropion SR, 150 mg/day, combined with CBT, may facilitate smoking reduction in patients with schizophrenia while stabilizing psychiatric symptoms during a quit attempt.", "Evidence that major depression can be a significant hindrance to smoking cessation prompted this examination of the usefulness of sertraline as a cessation aid for smokers with a history of major depression. Specifically, sertraline's efficacy for smoking abstinence and its effects on withdrawal symptoms were evaluated.\n The study design included a 1-week placebo washout, a 9-week double-blind, placebo-controlled treatment phase followed by a 9-day taper period, and a 6-month drug-free follow-up. One hundred thirty-four smokers with a history of major depression were randomly assigned to receive sertraline (N=68) or matching placebo (N=66); all received intensive individual cessation counseling during nine clinic visits.\n Sertraline treatment produced a lower total withdrawal symptom score and less irritability, anxiety, craving, and restlessness than placebo. However, the abstinence rates did not significantly differ between treatment groups: 28.8% (19 of 66) for placebo and 33.8% (23 of 68) for sertraline at the end of treatment and 16.7% (11 of 66) for placebo and 11.8% (eight of 68) for sertraline at the 6-month follow-up. No moderating effects of single or recurrent major depression, depressed mood at baseline, nicotine dependence level, or gender were observed.\n Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind, placebo-controlled study. However, given that the end-of-treatment abstinence rate for the placebo group was much higher than expected, it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline.", "African Americans disproportionately experience greater smoking attributable morbidity and mortality. Few clinical trials for smoking cessation in African Americans have been conducted, despite a different profile of both smoking and quitting patterns.\n To compare a sustained-release form of bupropion hydrochloride (bupropion SR) with placebo for smoking cessation among African Americans.\n Randomized, double-blind, placebo-controlled trial conducted from February 11, 1999, to December 8, 2000, of 600 African American adults treated at a community-based health care center. Volunteers, who smoked 10 or more cigarettes per day were recruited by targeted media and health care professionals.\n Participants were randomly assigned to receive 150 mg of bupropion SR (n = 300) or placebo (n = 300) twice daily for 7 weeks. Brief motivational counseling was provided in-person at baseline, quit day, weeks 1 and 3, end of treatment (week 6), and by telephone at day 3 and weeks 5 and 7.\n Biochemically confirmed 7-day point prevalence abstinence at weeks 6 and 26 following quit day.\n Using intention-to-treat procedures, confirmed abstinence rates at the end of 7 weeks of treatment were 36.0% in the bupropion SR group and 19.0% in the placebo group (17.0 percentage point difference; 95% confidence interval, 9.7-24.4; P<.001). At 26 weeks the quit rates were 21.0% in the treatment and 13.7% in the placebo groups (7.3 percentage point difference; 95% confidence interval, 1.0-13.7; P =.02). Those taking bupropion SR experienced a greater mean reduction in depression symptoms at week 6 (2.96 [9.45] vs 1.13 [8.84]) than those taking placebo, and after controlling for continuous abstinence, those taking bupropion SR also gained less weight than those taking placebo.\n Bupropion SR was effective for smoking cessation among African Americans and may be useful in reducing the health disparities associated with smoking.", "To investigate the efficacy of maintenance treatment with bupropion and/or nicotine gum for reducing smoking relapse.\n A 48-week study was conducted at a university-based smoking cessation clinic between February 2001 and October 2005. A total of 588 smokers received bupropion and nicotine patch in 8 weeks of open-label treatment (OLT); 289 abstainers during the last 4 weeks of OLT were randomized in double-blind placebo-controlled fashion to one of four arms for 16 weeks of maintenance treatment (MT) followed by 24 weeks of non-treatment follow-up (NTFU).\n Bupropion (300 mg/day) and 2 mg nicotine gum, used alone or combined, and comparable placebo pill and placebo gum. Behavioral counseling at all visits.\n Time to relapse (TTR) from randomization. Relapse is defined as the first 7 consecutive days of smoking. Abstinence verified by carbon monoxide <or= 8 parts per million.\n TTR was longer with extended active treatments compared to placebo (median days to relapse: bupropion + placebo = 136, nicotine + placebo = 98, bupropion + nicotine = 90, double placebo = 71). Hazard ratios (HR) for relapse were statistically significant for bupropion + placebo versus double placebo during MT (HR = 0.59, 95% CI = 0.37-0.92) and to the end of NTFU (HR = 0.66, 95% CI = 0.42-0.96). However, bupropion's advantage dissipated upon stopping the drug. Gum use was low, preventing a valid assessment; but analysis restricted to gum users suggested a weak effect of extended nicotine gum.\n Maintenance treatment with bupropion exerted a modest benefit for preventing smoking relapse; the optimum duration of bupropion treatment was unclear. Further research is needed to ascertain the merits of extended use of nicotine gum, other nicotine replacement agents and other treatments known to aid smokers for preventing relapse once abstinence is achieved.", "To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD).\n Six hundred twenty-nine subjects with CVD who smoked >/=10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150 mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study.\n Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; P<0.001). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, P<0.001). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 (P<0.001). In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants (n=36) discontinued study medication due to an adverse event (bupropion SR, n=17; placebo, n=19).\n After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking populations.", "To evaluate bupropion SR for smoking cessation in physicians and nurses.\n This double-blind prospective 26-center, 12-country trial randomized 687 subjects to smoking cessation counselling with bupropion SR or placebo for 7 weeks. The participants were followed for 52 weeks.\n Bupropion SR was superior to placebo (50% vs 40%, P=0.013) on the 4-week primary outcome variable. Due to a high placebo response in this health care population, statistical differences were not maintained after treatment was discontinued.\n Bupropion SR is effective and well tolerated in health care professionals. Relapse prevention measures are needed to attain long-term abstinence.", "Bupropion hydrochloride is recommended for smoking cessation; however, there have been relatively few clinical trials examining its efficacy.\n A total of 244 current smokers were enrolled in an outpatient randomized blinded smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center, San Francisco, Calif. Of the 244 participants, 121 received a 7-week course of bupropion and 123 received placebo. All participants received 2 months of transdermal nicotine replacement therapy and 3 months of cognitive-behavioral counseling. We determined on-medication treatment, end-of-medication treatment, 3-month, 6-month, and 1-year quit rates.\n During treatment with bupropion vs placebo, there was a trend toward increased quit rates among participants randomized to bupropion; the self-reported end-of-medication treatment quit rates were 64% for the bupropion group vs 57% for the placebo group (P =.23). The trend favoring bupropion persisted at 3 months of follow-up (P =.12) but was not apparent at 6 months and 1 year of follow-up (both P>.78). The 12-month quit rates, validated by either saliva cotinine or spousal proxy, were 22% in the bupropion group and 28% in the placebo group (P =.31). Based on biochemical validation, 19% of the bupropion group vs 24% of the placebo group had quit smoking by 1 year (P =.36).\n In this randomized blinded trial of mostly veteran participants, the addition of a brief 7-week bupropion trial to treatment with nicotine replacement therapy and counseling did not significantly increase smoking cessation rates.", "Adolescent smokers (N = 211) were randomized to 1 of 2 groups: (a) nicotine patch plus bupropion SR (sustained release; 150 mg per day) or (b) nicotine patch plus placebo. Group skills training sessions were conducted each week by research staff. Abstinence rates at Weeks 10 and 26 were as follows: (a) patch plus bupropion, 23% and 8%, (b) patch plus placebo, 28% and 7%. Despite the lack of a treatment effect, a large majority of adolescents in both treatment groups reduced their consumption to a few cigarettes per day or less and maintained this reduction over time. Similarly, an examination of survival curves revealed that by the end of treatment many had managed to avoid a return to daily smoking. These findings are encouraging and suggest new avenues for research. For example, treatments of the kind examined in this report, augmented by extended maintenance therapies, may yield higher long-term success rates.", "This study was conducted to evaluate the effect of bupropion sustained-release (SR) on smoking cessation in patients with chronic posttraumatic stress disorder (PTSD). Fifteen veterans with chronic PTSD who desired to stop smoking enrolled in a 12-week double-blind evaluation of bupropion SR and placebo. Patients were randomly assigned in a 2:1 ratio to receive either bupropion SR or placebo. Bupropion SR was initiated at 150 mg daily for 3 or 4 days and increased to a final dose of 150 mg twice daily (300 mg daily total). Ten patients received bupropion SR and five received placebo. Nine of the patients who received bupropion SR were already being treated with at least one other psychotropic medication. One of the ten patients did not complete the study because of medication side effects. Eighty percent of patients receiving bupropion SR successfully stopped smoking by the end of week 2, and 6 (60%) of these 10 maintained smoking cessation at the study endpoint (week 12). At the 6-month follow-up, 40% of the patients (4 of 10) who received bupropion SR maintained smoking cessation. One (20%) of the five patients who received placebo stopped smoking and maintained smoking cessation at the 6-month follow-up. Bupropion SR was generally well-tolerated in combination with other psychotropic medications. Bupropion SR may be effective in helping patients who desire to quit smoking and who also have a concomitant anxiety disorder, such as PTSD.", "In this double-blind, placebo-controlled smoking cessation treatment study, 608 participants were randomly assigned to receive active bupropion and active 4-mg gum (AA, n = 228), active bupropion and placebo gum (AP, n = 224), or placebo bupropion and placebo gum (PP, n = 156). Relative to the PP group, the AA and AP groups were each significantly more likely to be abstinent at 1 week, end of treatment, and 6 months but not at 12 months postquit. After the first week postquit there were no differences in abstinence rates between the AA and AP groups. We found no significant individual difference variables that moderated outcome beyond 1 week postquit.", "Gender data for bupropion suggest that it may be a particularly effective smoking cessation medication for women. It is not known whether the efficacy of this pharmacotherapy differs as a function of the psychotherapy with which it is administered. This study used a two level factorial design to examine the independent and interactive effects of medication (bupropion 300 mg/day vs. placebo) and psychotherapy (cognitive-behavioral therapy [CBT] vs. supportive therapy [ST]). In addition to testing the hypothesis that bupropion with CBT would be most effective of all the treatments, we examined medication compliance and its role in the efficacy of bupropion. Participants were 154 women, aged at least 30 years and smoking more than 10 cigarettes/day. Compliance with study medication was assessed using Medication Event Monitoring Systems (MEMS) over 7 weeks of treatment. Psychological interventions were delivered in 60-min weekly group sessions. Longitudinal analysis of abstinence outcomes from end of treatment (EOT) through 12 months after treatment revealed a significant interaction of medication and therapy. Higher abstinence rates at EOT and 3-, 6-, 9-, and 12-month follow-ups were observed when bupropion was delivered concurrently with CBT (44%, 24%, 30%, 23%, 17%) rather than with ST (18%, 1%, 8%, 5%, 2%). The bupropion-CBT combination, however, was not clearly superior to placebo, regardless of therapy assignment. Higher rates of medication compliance were positively predictive of abstinence, and this effect was most evident in the placebo condition. Findings provide only modest support for CBT as the preferred type of intensive therapy in conjunction with bupropion in women.", "Smoking cessation rates with current therapy are suboptimal. Tricyclic antidepressants improve cessation rates. We hypothesized that addition of nortriptyline hydrochloride to transdermal nicotine would enhance cessation rates.\n We conducted a randomized, double-blind, placebo-controlled trial at a Department of Veterans Affairs medical center. Subjects were aged 18 to 65 years, smoked 10 or more cigarettes per day, and did not have current major depression. Nortriptyline hydrochloride or matched placebo was started at 25 mg 14 days before quit day, titrated to 75 mg/d as tolerated, and continued for 12 weeks after quit day. Transdermal nicotine (21 mg/d) was started on quit day and continued for 8 weeks. The behavioral intervention consisted of 12 brief, individual visits. Withdrawal symptoms were measured by means of a daily diary, and smoking cessation was defined as self-reported abstinence, expired carbon monoxide level of 9 ppm or less, and a 6-month urine cotinine level less than 50 ng/mL (284 nmol/L).\n A total of 158 patients were randomized (79 to nortriptyline and 79 to placebo). There was no significant reduction in withdrawal symptoms. The cessation rates at 6 months were 23% (18/79) and 10% (8/79), respectively (absolute difference, 13%; 95% confidence interval, 1.3%-24.5%; P = .052). Nortriptyline caused frequent side effects, including dry mouth (38%) and sedation (20%).\n Nortriptyline combined with transdermal nicotine resulted in an increased cessation rate with little effect on withdrawal symptoms. This combination may represent an option for smokers in whom standard therapy has failed.", "Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or \"target quit date\") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less.\n At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups.\n A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year.", "To assess the effectiveness of moclobemide on smoking cessation and abstinence in heavy, dependent smokers. There is a strong association between smoking and depression, especially in dependent smokers. It was hypothesized that smoking is a self-medication to treat depression. Cigarette smoke has monoamine oxidase (MAO)-inhibitory properties, and smokers have lower MAO activity than non-smokers.\n We used a randomized, double-blind, placebo-controlled parallel-group study. Placebo or moclobemide, 400 mg/day for 2 months and 200 mg/day during the third month, was given. Main outcome measures were self-reported and biochemically verified (plasma cotinine levels, < 20 ng/ml) abstinence rate. Secondary outcome measures were withdrawal symptoms, Montgomery-Asberg Depression Rating Scale, Hamilton anxiety rating scores, platelet MAO-B activity, and plasma dihydroxyphenylglycol as a measure of MAO-A activity.\n Eighty-eight smokers were randomized to receive moclobemide (n = 44) or placebo (n = 44). The continuous self-reported abstinence rate was higher with moclobemide than with placebo (intention-to-treat analysis until the end point, 6 months: p < 0.05; until the end of follow-up, 1 year: p = 0.09). The abstinence rate according to plasma cotinine levels showed a trend to effectiveness of moclobemide (end point: p = 0.13; follow-up: p = 0.12). Platelet MAO-B activity increased after smoking cessation but without a significant difference. Plasma dihydroxyphenylglycol levels did not change in the placebo group but decreased dose dependently in the moclobemide group. No difference occurred for withdrawal symptoms, Montgomery-Asberg Depression Rating Scale, and Hamilton anxiety scores. Cessation of moclobemide had no adverse effect. More subjects reported insomnia with moclobemide (n = 16) than with placebo (n = 3).\n In this preliminary study, the reversible, selective MAO inhibitor moclobemide facilitated smoking cessation in highly dependent smokers. Further studies with substantially more smokers are needed to evaluate the role of MAO inhibitors in smoking cessation and abstinence in smokers with high nicotine dependence.", "Smoking is a risk factor for complications during and after surgery, but most smokers are unable to quit before elective surgery. We tested the efficacy of bupropion in improving smoking cessation rates in this setting by enrolling 47 patients from the elective surgery waiting list in a double-blind randomised controlled trial. Patients receiving bupropion had a lower daily cigarette consumption at the time of hospital admission, median (IQR) cigarettes per day: 6 (2-7) vs. 15 (9-20), p = 0.046. They also had a reduction in end-expired carbon monoxide (p = 0.004), a known contaminant of cigarette smoke, and increased arterial oxygen saturation on pulse oximetry (p = 0.011). They were more likely to have stopped smoking at the 3-week visit (p = 0.036), but not at the 6-week visit (p = 0.25) or at the time of hospital admission for surgery (p > 0.99). This study found that smokers waiting for elective surgery are more likely to reduce or stop smoking when treated with bupropion.", "To determine whether sustained-release bupropion promotes smoking reduction leading to smoking cessation among persons who wish to reduce their amount of smoking, but who are unwilling to quit or who perceive themselves as being unable to quit.\n Current smokers were assigned randomly to receive either sustained-release bupropion (150 mg twice daily) or matching placebo. During an initial 6-month smoking reduction phase, those who were willing to quit entered a 7-week cessation phase, during which study medication was continued.\n Four-week continuous abstinence rates were 14% (41/295) in the bupropion group and 8% (25/299) in the placebo group (P = 0.02) during treatment. However, this benefit did not continue after treatment was stopped; subsequent continuous abstinence rates were 7% (20/295) in the bupropion group and 5% (16/299) in the placebo group (P = 0.50). Similar proportions of subjects entered the cessation phase in both treatment groups (38% [n = 113] of those in the bupropion group and 34% [n = 101] of those in the placebo group), although the time until a cessation attempt was shorter for those taking bupropion (median, 64 days vs. 118 days, P = 0.008). The extent of smoking reduction (measured by urinary cotinine concentrations) among the 327 subjects who did not enter the cessation phase was significantly greater (P <0.05) in those treated with bupropion during the reduction treatment phase, but not during the month 12 follow-up visit (P = 0.25).\n Sustained-release bupropion, when used in smokers initially not willing to make a cessation attempt, can help sustain smoking reduction while subjects are on active medication, reduce the time until the next cessation attempt, and increase short-term abstinence rates. However, these benefits were modest and not sustained after bupropion was discontinued.", "To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy. Participants and\n Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention). and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment.\n Of 578 subjects, 31% were abstinent from smoking at the end of nicotine patch therapy. Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase, 28% and 25% were not smoking at 6 months (the end of the medication phase) for bupropion and placebo, respectively (P =.73). For those still smoking at the end of nicotine patch therapy, 3.1% and 0.0% stopped smoking with bupropion or placebo, respectively (P =.12).\n Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting. Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy. Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy.", "The authors evaluated the efficacy of fluoxetine hydrochloride (Prozac; Eli Lilly and Company, Indianapolis, IN) as an adjunct to behavioral treatment for smoking cessation. Sixteen sites randomized 989 smokers to 3 dose conditions: 10 weeks of placebo, 30 mg, or 60 mg fluoxetine per day. Smokers received 9 sessions of individualized cognitive-behavioral therapy, and biologically verified 7-day self-reported abstinence follow-ups were conducted at 1, 3, and 6 months posttreatment. Analyses assuming missing data counted as smoking observed no treatment difference in outcomes. Pattern-mixture analysis that estimates treatment effects in the presence of missing data observed enhanced quit rates associated with both the 60-mg and 30-mg doses. Results support a modest, short-term effect of fluoxetine on smoking cessation and consideration of alternative models for handling missing data.", "The alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel alpha4beta2 nAChR partial agonist, may be beneficial for smoking cessation.\n To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo.\n Randomized, double-blind, parallel-group, placebo- and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (> or =10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising.\n Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n = 352), bupropion SR titrated to 150 mg twice per day (n = 329), or placebo (n = 344) orally for 12 weeks, with 40 weeks of nondrug follow-up.\n Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52.\n For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0% for varenicline vs 17.7% for placebo (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5% for bupropion SR (OR, 1.93; 95% CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95% CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9% for varenicline vs 8.4% for placebo (OR, 3.09; 95% CI, 1.95-4.91; P<.001) and vs 16.1% for bupropion SR (OR, 1.46; 95% CI, 0.99-2.17; P = .057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1%]) and insomnia (72 receiving bupropion SR [21.9%]).\n Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks.\n clinicaltrials.gov Identifier: NCT00141206.", "Smoking cessation rates with current therapy are suboptimal. One class of drugs that may improve cessation is the tricyclics.\n To add nortriptyline hydrochloride to a behavioral smoking cessation program to enhance cessation rates and reduce withdrawal symptoms.\n We conducted a randomized, double-blind, placebo-controlled trial at an affiliated Department of Veterans Affairs Medical Center and an Army Medical Center. Subjects were aged 18 through 70 years, smoked 10 or more cigarettes per day, and were without current major depression. Nortriptyline hydrochloride or matched placebo was started at 25 mg before bed 10 days prior to quit day and titrated to 75 mg/d or to the maximal tolerated dose. The behavioral intervention consisted of 2 group sessions and 12 individual follow-up visits. Withdrawal symptoms were measured using a daily diary, and smoking cessation was defined as self-reported abstinence, expired carbon monoxide of 9 ppm or less, and a 6-month urine cotinine level of less than 50 ng/mL.\n A total of 214 patients were randomized (108 to nortriptyline and 106 to placebo). There was a significant reduction in several withdrawal symptoms including anxious/tense, anger/irritability, difficulty concentrating, restlessness, and impatience by day 8 after quit day in the nortriptyline group. The cessation rate at 6 months was 15 (14%) of 108 and 3 (3%) of 106, respectively (P = .003; absolute difference, 11%; 95% confidence interval, -18% to -4%). Nortriptyline caused frequent adverse effects, including dry mouth (64%) and dysgeusia (20%).\n We conclude that nortriptyline led to an increased short-term cessation rate compared with placebo. In addition, there were significant, but relatively small, reductions in withdrawal symptoms. Nortriptyline may represent a new therapeutic approach to smoking cessation.", "Bupropion is a first-line pharmacological aid for smoking cessation; however, no clinical trials have been conducted in a general population of hospitalized smokers.\n We enrolled 85 smokers in a hospital-based randomized smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center. A total of 42 participants received a 7-week course of sustained-release bupropion and 43 participants received placebo. All participants received cognitive-behavioral counseling. We screened 14,997 patients, of whom 25% were current smokers. Of the 536 smokers who met the entry criteria, 451 opted not to enroll. We determined on-medication, end-of-medication, 3-month, and 6-month smoking cessation rates.\n At the end of 7 weeks of drug treatment, self-reported quit rates were equivalent in the bupropion and placebo arms, 37% versus 33%, respectively (p = .82). The validated quit rates for the bupropion and placebo groups were 27% versus 29%, respectively (p = 1.00). At 6 months, the self-reported quit rates were 29% in the bupropion group and 41% in the placebo group (p = .36). In a comparison of 6-month quit rates, validated either by salivary cotinine or by spousal proxy, we found nonsignificantly higher quit rates in the placebo group than in the bupropion group, 31% versus 15% (p = .12).\n The addition of sustained-release bupropion to counseling did not increase quit rates, but the study was underpowered. Because of the secular trend toward shorter hospital stays, recruitment was very difficult, raising questions regarding the feasibility of future hospital-based smoking cessation trials and interventions.", "The study was a randomized placebo-controlled trial testing whether fluoxetine selectively enhances cessation for smokers with a history of depression. Euthymic smokers with (H+, n = 109) or without (H-, n = 138) a history of major depression received 60 mg fluoxetine or placebo plus group behavioral quit-smoking treatment for 12 weeks. Fluoxetine initially enhanced cessation for H+ smokers (p = .02) but subsequently impaired cessation regardless of depressive history. Six months after quit date, fluoxetine-treated participants were 3.3 times more likely to be smoking (p = .02). Further research is warranted to determine why high-dose fluoxetine produces continuing effects that oppose tobacco abstinence.\n Copyright 2007 APA, all rights reserved.", "Smokers (N = 224) were randomized to 1 of 3 groups: (a) transdermal system (TNS) + placebo; (b) TNS + paroxetine (20 mg); (c) TNS + paroxetine (40 mg). Assignment to treatment was double-blind. Nicotine patch (TNS) treatment was provided for 8 weeks; paroxetine or placebo was provided for 9 weeks. Abstinence rates at Weeks 4, 10, and 26 were as follows: (a) TNS + placebo: 45%, 36%, and 25%; (b) TNS + paroxetine (20 mg): 48%, 33%, and 21%; (c) TNS + paroxetine (40 mg): 57%, 39%, and 27%. The differences were not statistically significant. The combined treatment was more effective in reducing both craving and depression symptoms associated with smoking cessation. A subgroup analysis comparing compliant participants was also conducted. Abstinence rates at Weeks 4, 10, and 26 were as follows: (a) TNS + placebo: 46%, 35%, and 24%; (b) TNS + paroxetine (20 mg): 64%, 43%, and 33%; (c) TNS + paroxetine (40 mg): 74%, 51%, and 38%. The differences between paroxetine groups and placebo at Week 4 were statistically significant. Although paroxetine may add value to the current standard of care in excess of potential risk, more conclusive evidence is needed.", "A prospective randomized study was undertaken to assess the effectiveness and side effect profiles of nicotine patch and bupropion therapies for smoking cessation.\n Three hundred and fifty patients were referred to our smoking cessation program in the Department of Pulmonary Diseases, Gaziantep University between September 2002 and July 2003. Of these, only 131 patients fulfilled the trial criteria. We randomized the patients into nicotine patch (n=50), bupropion (n=50) and control groups (n=31). Cases were followed up for 24 weeks. Questionnaires including the Fagerstrom test for nicotine dependence and Beck Depression Inventory were carried out at initial evaluation. Declaration of quitting and exhaled carbon monoxide level less than 10 ppm was accepted as success criteria.\n Success rates were 26% for nicotine patch group, 26% for bupropion and 16% for control group at the end of the 24th week (p=0.56). Beck depression inventory scores did not differ significantly between the groups, however none of the cases with scores greater than 13 succeeded regardless of the group. Mean body weight at baseline and change at 6 months did not differ significantly between the groups. Sleep disturbance was significantly more common in nicotine patch and bupropion groups than the control group (p=0.008).\n The present study reinforces the role of medical doctors and importance of close follow up in smoking cessation, and directed counseling is quite as effective as pharmacologic therapy and is the sole approach without any adverse effects.", "The authors present results of a randomized clinical trial of the efficacy of extended treatment with bupropion SR in producing longer term cigarette smoking cessation. Adult smokers (N = 362) received open-label treatment (11 weeks) that combined relapse prevention training, bupropion SR, and nicotine patch followed by extended treatment (14 weeks) with bupropion SR or matching placebo. Abstinence percentages were relatively high (week 11: 52%; week 25: bupropion, 42%; placebo, 38%; week 52: bupropion, 33%; placebo, 34%), but bupropion SR did not surpass placebo. Gender and baseline craving level were identified as significant, independent moderators of treatment response. Men were more likely to abstain than women (week 11: 59% vs. 43%, p = .001; week 25: 48% vs. 31%, p = .001; week 52: 39% vs. 27%, p = .01). Because most smokers suffer relapse with any current cessation treatment, the comparatively high abstinence percentages achieved in this trial are of interest.\n Copyright 2006 APA", "Smoking cessation attempts are often complicated by dysphoria/depression, weight gain, craving, and other nicotine withdrawal symptoms. Fluoxetine's antidepressant and anorectant properties, along with its capacity to attenuate compulsive behavior, suggest that this medication might facilitate smoking cessation treatment. We examined the effect of fluoxetine on smoking cessation in the context of a program that included group cognitive-behavioral therapy (six weeks) and transdermal nicotine patch(ten weeks). In a double-blind randomized trial of fluoxetine for smoking cessation, 150 daily smokers were assigned to placebo (n=48), 20 mg (n=51), or 40 mg fluoxetine (n=51). Fluoxetine did not significantly improve smoking cessation rates, either for those with or without major depressive disorder(MDD)histories or elevated current depression. Our results suggest that fluoxetine may moderate withdrawal symptoms, even if that was not manifested in improved smoking cessation rates. Our results, however, clearly favor the use of fluoxetine if weight gain is a major clinical obstacle to smoking cessation.", "Smoking rates are high in indigenous populations and contribute to their poor health. In New Zealand the indigenous Maori population has a high rate of smoking, with around 50% of adults being smokers compared with 20% of the adult European population. A study was undertaken to determine whether bupropion is effective in the treatment of smoking cessation in the indigenous Maori population in New Zealand.\n A randomised, placebo controlled, double blind, parallel group study was performed in 134 Maori smokers aged 16-70 years who smoked more than 10 cigarettes per day. The main outcome measures were continued abstinence from smoking at 3 and 12 months.\n At each time point continued abstinence was better for the subjects allocated to bupropion, with a risk ratio for abstinence over all time points of 2.44 (95% CI 1.22 to 4.88). The rates of continued abstinence in the bupropion and placebo groups at 3 months were 44.3% and 17.4%, respectively, with a risk ratio of 2.54 (95% CI 1.30 to 5.00). The corresponding figures at 12 months were 21.6% and 10.9%, respectively, with a risk ratio of 1.99 (95% CI 0.79 to 5.00).\n Bupropion is an effective treatment for smoking cessation in the indigenous Maori population in New Zealand.", "Sustained-release bupropion hydrochloride and nortriptyline hydrochloride have been shown to be efficacious in the treatment of cigarette smoking. It is not known whether psychological intervention increases the efficacy of these antidepressants. This study compared both drugs with placebo. It also examined the efficacy of these 2 drugs and placebo with and without psychological intervention.\n This was a 2 (medical management vs psychological intervention) x 3 (bupropion vs nortriptyline vs placebo) randomized trial. Participants were 220 cigarette smokers. Outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 36, and 52.\n Psychological intervention produced higher 7-day point-prevalence rates of biochemically verified abstinence than did medical management alone. With the use of point-prevalence abstinence, both nortriptyline and bupropion were more efficacious than placebo. On rates of 1-year continuous abstinence, the 2 drugs did not differ from each other or from placebo. Psychological intervention did not differ from medical management alone on rates of 1-year continuous abstinence.\n Both nortriptyline and bupropion are efficacious in producing abstinence in cigarette smokers. Similarly, psychological intervention produces better abstinence rates than simple medical management. Both drugs, and psychological intervention, have limited efficacy in producing sustained abstinence. The data also suggest that combined psychological intervention and antidepressant drug treatment may not be more effective than antidepressant drug treatment alone.", "Smoking cessation after myocardial infarction reduces cardiovascular mortality, but many smokers cannot quit despite state-of-the-art counseling intervention. Bupropion is effective for smoking cessation, but its safety and efficacy in hospitalized smokers with acute cardiovascular disease is unknown.\n A five-hospital randomized double-blind placebo-controlled trial assessed the safety and efficacy of 12 weeks of sustained-release bupropion (300 mg) or placebo in 248 smokers admitted for acute cardiovascular disease, primarily myocardial infarction and unstable angina. All subjects had smoking counseling in the hospital and for 12 weeks after discharge. Cotinine-validated 7-day tobacco abstinence, cardiovascular mortality, and new cardiovascular events were assessed at 3 months (end-of-treatment) and 1 year.\n Validated tobacco abstinence rates in bupropion and placebo groups were 37.1% vs 26.8% (OR 1.61, 95% CI, 0.94-2.76; P=.08) at 3 months and 25.0% vs 21.3% (OR, 1.23, 95% CI, 0.68-2.23, P=.49) at 1 year. The adjusted odds ratio, after controlling for cigarettes per day, depression symptoms, prior bupropion use, hypertension, and length of stay, was 1.91 (95% CI, 1.06-3.40, P=.03) at 3 months and 1.51 (95% CI, 0.81-2.83) at 1 year. Bupropion and placebo groups did not differ in cardiovascular mortality at 1 year (0% vs 2%), in blood pressure at follow-up, or in cardiovascular events at end-of-treatment (16% vs 14%, incidence rate ratio [IRR]1.22 (95% CI: 0.64-2.33) or 1 year (26% vs 18%, IRR 1.56, 95% CI 0.91-2.69).\n Bupropion improved short-term but not long-term smoking cessation rates over intensive counseling and appeared to be safe in hospitalized smokers with acute cardiovascular disease." ]

[ "6799266", "2251616", "3969207", "3901650", "366085", "333855" ]

[ "[Bromocriptin in the treatment of progressive stages of Parkinson's disease (author's transl)].", "Adjunctive therapy with bromocriptine in Parkinson's disease.", "Low dosages of bromocriptine added to levodopa in Parkinson's disease.", "Effects of bromocriptine on parkinsonism. A nation-wide collaborative double-blind study.", "Treatment of the on-off syndrome in Parkinsonism with low dose bromocriptine in combination with levodopa.", "Bromocriptine versus placebo in levodopa treated patients with Parkinson's disease." ]

[ "Forty patients with severe Parkinson's disease (23 men, 17 women) who had been treated for six years with L-dopa-decarboxylase inhibitor, were part of a placebo-controlled double-blind trial to test the effectiveness of bromocriptin. In all patients the effectiveness of L-dopa had been decreasing, 34 patients had L-dopa-induced dyskinesias, 35 \"on-off\" symptoms. Bromocriptin dosage was gradually increased to a total dose of 30 - 40 mg daily. This led to a 25% reduction in L-dopa requirements. The symptoms of Parkinson's disease were favourably influenced, with rigor, tremor and also walking disturbances responding better than bradykinesia of the hands. At the same time, there was a marked prolongation of the periods of good mobility (\"on\" time) from 7 to 10.8 hours without influence on other \"on-off\" symptoms such as paradoxical akinesia. Two patients had to be excluded from the trial because the treatment caused side effects (orthostatic hypotension, exogenous psychotic symptoms). Other side effects, such as nausea and mild forms of collapse, could be controlled by drugs.", "Patients with moderately severe Parkinson's disease complicated by the adverse effects of chronic levodopa use benefited from the addition of bromocriptine (Parlodel; Sandoz) in doses up to 26 mg daily, which allowed an approximate 30% reduction of levodopa dose. This resulted in a significant decrease in the amount of levodopa side-effects while maintaining or improving the original parkinsonian clinical stage. Increased effectiveness in these patients was not associated with increased dosage beyond 25-30 mg daily. When the doses of bromocriptine were increased slowly, the adverse reactions were minor and usually transient.", "Thirty-six patients with Parkinson's disease, on levodopa, were admitted to a double-blind, parallel, 40-week study of adjunct bromocriptine in dosages increased by 2.5 mg every 4 weeks. A 37% improvement of the mean neurologic deficit score was obtained at the maximal daily dosage of 20 mg. Improvement was greatest in patients with mild disease. The wearing-off effect, off-dose abnormal involuntary movements, and leg pains, associated with levodopa, improved in over 70% of patients at an average dosage of 13 mg. Only 15% of patients had adverse reactions severe enough to necessitate discontinuance of the drug. Abnormalities of mental state were less severe than expected, but two patients had exacerbations of angina pectoris.", "The effects of bromocriptine in patients with Parkinson's disease manifesting various problems in levodopa therapy were tested in a double-blind manner with the collaboration of 59 institutions. The slow and low principle was in part adopted. Either bromocriptine or placebo was added to levodopa. Twenty-nine % of the bromocriptine-treated patients (n = 108), in contrast to 14.8% of the placebo-treated (n = 108), showed either marked or moderate improvement (P less than 0.05). Twenty to 37% improvement was noted in most of the symptoms studied in those treated with bromocriptine. The significant superiority of bromocriptine was also noted in the effects on wearing-off phenomena and frozen gait. No irreversible side effects were noted. It is concluded that bromocriptine is useful in patients who are manifesting various difficulties in levodopa therapy. Our results are comparable to those using higher maintenance doses. Dopamine antagonistic actions were not observed. This is unlike the case with experimental animals.", "The addition of bromocriptine, given in divided doses up to 30 mg per day, to conventional anti-Parkinsonism therapy has been studied in a double-blind placebo controlled clinical trial in 11 patients with Parkinsonism with the \"on-off\" syndrome. Four patients withdrew because of side effects. Of the seven remaining, three had clinical benefit from bromocriptine with reduction in severity and frequency of fluctuations. There was, however, no statistically significant benefit of bromocriptine when the group as a whole was assessed in terms of severity or frequency of fluctuations measured by three different methods. The mean frequency of major fluctuations on placebo was 2.9/day and on bromocriptine 1.8/day (P less than 0.1 greater than 0.05). There appears to be a limited role for bromocriptine as additional therapy in the management of some patients with the on-off syndrome.", "Twenty patients with idiopathic parkinsonism who had been on optimal levodopa therapy for at least 3 months prior to the investigation and where effect of the treatment was decreasing or side effects were increasing, were treated with bromocriptine in a double-blind crossover trial during a 12 + 12 weeks period. Reduction in disability scores was found significant. Hyperkinesia was more frequent in the bromocriptine period than in the placebo period, but reduction of dose in six patients for this reason was not followed by deterioration. Both hyperkinesia and other side effects disappeared after dose reduction. Doses were 2.5 mg-40 mg. Bromocriptine seems a valuable supplement to previous therapy in these patients." ]

[ "18450876", "11930093", "3234607", "1340834", "11113837", "11433088", "6525357", "15678233", "3717993", "9797593", "3430263", "12674840", "8813983", "8957948", "16541716", "1678797", "14516239", "2299491", "6630328" ]

[ "Behavioral therapy for childhood constipation: a randomized, controlled trial.", "Treatment of childhood encopresis: a randomized trial comparing three treatment protocols.", "Biofeedback training for patients with myelomeningocele and fecal incontinence.", "[The usefulness of biofeedback in children with encopresis. A preliminary report].", "Lack of benefit of laxatives as adjunctive therapy for functional nonretentive fecal soiling in children.", "The effect of anorectal manometry on the outcome of treatment in severe childhood constipation: a randomized, controlled trial.", "A components analysis of biofeedback in the treatment of fecal incontinence.", "Assessment of the effectiveness of biofeedback in children with dyssynergic defecation and recalcitrant constipation/encopresis: does home biofeedback improve long-term outcomes.", "Factors associated with outcome in management of defecation disorders.", "Randomised controlled trial of biofeedback training in persistent encopresis with anismus.", "Evaluation of biofeedback in childhood encopresis.", "Efficiency of biofeedback therapy for chronic constipation in children.", "Biofeedback training in treatment of childhood constipation: a randomised controlled study.", "Randomised trial of biofeedback training for encopresis.", "[Usefulness of biofeedback treatment in children with chronic functional constipation].", "Randomised trial of laxatives in treatment of childhood encopresis.", "An Internet intervention as adjunctive therapy for pediatric encopresis.", "Modulation of abnormal defecation dynamics by biofeedback treatment in chronically constipated children with encopresis.", "A controlled trial of 'Senokot' in faecal soiling treated by behavioural methods." ]

[ "It has been suggested that the addition of behavioral interventions to laxative therapy improves continence in children with functional fecal incontinence associated with constipation. Our aim was to evaluate the clinical effectiveness of behavioral therapy with laxatives compared with conventional treatment in treating functional constipation in childhood.\n In this randomized, controlled trial conducted in a tertiary hospital in The Netherlands, 134 children aged 4 to 18 years with functional constipation were randomly assigned to 22 weeks (12 visits) of either behavioral therapy or conventional treatment. Primary outcomes were defecation frequency, fecal incontinence frequency, and success rate. Success was defined as defecation frequency of > or = 3 times per week and fecal incontinence frequency of < or = 1 times per 2 weeks irrespective of laxative use. Secondary outcomes were stool-withholding behavior and behavior problems. Outcomes were evaluated at the end of treatment and at 6-months follow-up. All of the analyses were done by intention to treat.\n Defecation frequency was significantly higher for conventional treatment. Fecal incontinence frequency showed no difference between treatments. After 22 weeks, success rates did not differ between conventional treatment and behavioral therapy (respectively, 62.3% and 51.5%), nor did it differ at 6 months of follow-up (respectively, 57.3% and 42.3%). The proportion of children withholding stools was not different between interventions. At follow-up, the proportion of children with behavior problems was significantly smaller for behavioral therapy (11.7% vs 29.2%).\n Behavioral therapy with laxatives has no advantage over conventional treatment in treating childhood constipation. However, when behavior problems are present, behavioral therapy or referral to mental health services should be considered.", "To compare short- and long-term effectiveness of three additive treatment protocols in children experiencing chronic encopresis.\n Children, 6 to 15 years of age, who experienced at least weekly fecal soiling for 6 months or longer were eligible for the study. Children were randomly assigned to a group that received intensive medical therapy (IMT), a group that received intensive medical therapy plus a behavior management program called enhanced toilet training (ETT), or a group that received intensive medical therapy with enhanced toilet training and external anal sphincter electromyographic biofeedback (BF). Data concerning toileting habits were collected for 14 consecutive days before an initial visit, and at 3, 6, and 12 months after initiation of therapy. All data were collected using a computerized voice-mail system that telephoned the families each day. At 12 months, children were classified as significantly improved (reduction in soiling, P < 0.001) or cured (<one fecal accident in 2 weeks).\n Eighty-seven children participated in the study, 72 boys and 15 girls. Mean age at enrollment was 8.6 +/- 2.0 years, and mean duration of symptoms was 58.2 +/- 38.5 months. At 12 months, the cure rates for the IMM, ETT, and BF groups were 36, 48, and 39, respectively (not significant). The improvement rates for these three groups were 45, 78, and 54, respectively (P < 0.05). These results were very stable over time (r > 0.90, P < 0.001 in each case). Response to treatment during the first 2 weeks of therapy was highly predictive of outcome at 3, 6, and 12 months (P < 0.0001). Children in the ETT group used less laxative medication (P < 0.04) and required fewer treatment contacts (P = 0.08) than children in the IMM group. All three treatments resulted in significant increases in daily bowel movements passed in the toilet and self-initiated toileting, and resulted in decreases in average daily soiling at 3, 6, and 12 months (P < 0.05).\n Enhanced toilet training is somewhat more effective in treating childhood encopresis than either intensive medical therapy or anal sphincter biofeedback therapy. Although similar total cure rates at 1 year can be expected with these three forms of therapy, enhanced toilet training results in statistically significant decreases in the daily frequency of soiling for the greatest number of children.", "This study evaluated the efficacy of biofeedback training for fecal in continence in patients with myelomeningocele. 12 patients were randomized to receive conventional treatment alone, or in conjunction with biofeedback. Anorectal manometric functions were evaluated before and after treatment, six and 12 months later. 16 control children were also studied. Three of eight patients in the biofeedback group and three of the four given conventional treatment alone reported greater than or equal to 75 per cent improvement in frequency of soiling 12 months later. Biofeedback training did not improve anal squeeze, rectal sensation or continence of rectal infused saline. The number of patients who improved in both treatment groups was not different.", "Children with encopresis (costiveness) have a social problem, and (BFB) offers them a valid therapeutic alternative. The present prospective study compares the advantages of this technique with conventional treatment in 21 patients, with average ages of 10.13 and 8.54 years in each group. The patients were studied by clinical, manometric and electromyographic parameters. Those treated with BFB showed clinical improvement, with manometric significant enhancement (p < 0.001) of the percentage of internal anal sphincter (IAE) relaxation, relaxation interval of the IAE and rectal sensation threshold (RST), on the other hand, patients treated by conventional therapy only improved the RST (p < 0.01). Biofeedback seems useful in the treatment of the child with encopresis.", "To determine whether the combination of laxative treatment and biofeedback therapy (BF) is more effective for management of functional nonretentive fecal soiling than biofeedback therapy alone.\n In a prospective nonblinded study, 48 children were randomized in 2 groups: treatment with oral laxatives (LAX) and 5 sessions of BF (BF + LAX) or 5 sessions of BF alone (BF) during a treatment intervention period of 7 weeks. Biofeedback was performed with perfused manometry catheters and rectal balloon distension. Training focused on awareness of balloon distension and instruction in correct defecation dynamics. Successful treatment was defined as <1 encopresis episode per 2 weeks.\n At the end of the intervention period, the number of encopresis episodes was significantly decreased in both groups: from 7 (2 to 24) to 2 (0 to 17) in the BF group and from 7 (3 to 25) to 2 (0 to 14) in the BF + LAX group. However, children given BF alone had significantly higher success rates than children treated with BF and additional oral laxatives (44% to 11%).\n There is no additional effect of laxative treatment in functional nonretentive fecal soiling. Children treated with BF in combination with laxatives showed a significantly lower success percentage compared with those treated with BF alone. These results suggest that children with functional nonretentive fecal soiling should be treated differently from children with constipation and encopresis.", "Approximately 50% of constipated children contract rather than relax the external sphincter complex during a defecation attempt. Although biofeedback training (BF) is able to change this defecation behavior, there is no additional effect of BF to conventional treatment (CT) on clinical outcome compared with CT alone. It has been postulated that the absence of a significant difference between these 2 treatment options might be because of a therapeutic, \"demystifying\" effect of performing anorectal manometry in conventionally treated children, necessary to obtain basal manometric data. The objective of this prospective, controlled, randomized study was to evaluate the effect of CT with 2 anorectal manometry sessions compared with CT alone (dietary advice, diary, toilet training, oral laxatives, and enemas) on clinical outcome.\n A total of 212 constipated children (143 boys) who were visiting a referral pediatric gastroenterologic practice were randomized prospectively to CT alone (115 patients) or to CT combined with 2 manometry sessions (CTM; 97 patients). Patients were included in the study when they fulfilled at least 2 of the 4 following criteria: stool frequency fewer than 3 per week, 2 or more soiling and/or encopresis episodes per week, periodic passage of very large amounts of stool every 7 to 30 days, or a palpable rectal or abdominal fecal mass. CT comprises dietary advice, a daily diary, toilet training, and oral laxative treatment preceded by rectal disimpaction with enemas on 3 consecutive days. During both manometries, the child and the parent could watch the tracing on the computer screen. No explanation was given to either the child or the parents during the procedure. When the procedure was finished, the tracings were clarified. Successful treatment was defined as a defecation frequency of 3 or more per week and fewer than 1 soiling/encopresis episode per 2 weeks and no use of laxatives.\n Only 4 and 2 children from the CT and CTM groups showed no soiling and/or encopresis, whereas 76% and 65%, respectively, reported the periodic passage of large stools. In 26% and 30% of the patients, a rectal scybalum was found on physical examination. The success rates at 6, 26, 52, and 104 weeks' follow-up were 4%, 24%, 32%, and 43% and 7%, 22%, 30%, and 35% in the CT and CTM group, respectively. No significant difference in success percentage was observed between the 2 groups at any time of follow-up with relative risks (CT/CTM) and 95% confidence intervals, respectively, of 0.55 (0.16-1.89), 1.13 (0.67-1.89), 1.07 (0.69-1.65), and 1.23 (0.81-1.85). A significant increase in defecation frequency was observed between the first (intake) and second visits, which was sustained at all subsequent visits and stages of follow-up in both groups (not significant). Also in relation to the first visit, a significant decrease in encopresis episodes was shown and a further slow but significant decrease at 52 weeks of follow-up in both groups. The manometric data obtained from the CTM group showed a low percentage of children with normal defecation dynamics, namely 28%, which (significantly) increased to 38% at the last manometry.\n Anorectal manometry combined with CT compared with CT alone did not result in higher success rates in chronically constipated children. Therefore, anorectal manometry has no additional demystifying or educational effect on clinical outcome in chronically constipated children. This observation together with the observation in the current and previous studies that no correlation was found between (achievement of) normal defecation dynamics and success and that no relation was observed between volume of urge or critical volume and success leaves no diagnostic or therapeutic role for anorectal manometry in chronic constipated children, except its use as a diagnostic test to exclude Hirschsprung's disease. A simple CT is successful in 30% of severely constipated children who are referred to a tertiary hospital, underscoring the importance of long-lasting and adequate laxative treatment.", "Fecal incontinence is a socially disabling symptom for which rectosphincteric biofeedback has been reported to be dramatically effective. The most commonly employed biofeedback procedure incorporates three separate and potentially effective components: exercise of the external sphincter muscle, training in discrimination of rectal sensations, and training synchrony of the internal and external sphincter responses. This paper reports the results of single case experiments employed with eight incontinent patients to examine the contributions of each of these components. All eight patients improved, but only one required the biofeedback procedure as it was originally described. Three responded to sensory discrimination training, one to exercise training, and one to the training of synchronous sphincteric responses; three recovered independently of the effects of biofeedback. Despite the achievement of continence, the rectosphincteric reflexes following treatment continued to be abnormal in every case. These findings suggest that the character of the external sphincter response to rectal distension is an unreliable index of sphincter function and that exercise and sensory discrimination training procedures are effective for some cases of fecal incontinence.", "The purpose of this study was to determine whether biofeedback benefits children with dyssynergic defecation and constipation/encopresis, and whether home biofeedback improves long-term outcomes. Thirty-six patients with chronic constipation who had failed at least 6 months of conventional treatment and demonstrated dyssynergic defecation at anorectal manometry were randomized to biofeedback in the laboratory alone (group 1, n=24) or in the laboratory and at home (group 2, n=12) and followed up at 2, 4, and a mean of 44 months. Thirty patients were available for long-term follow-up. Bowel movements increased in all from a mean of 1.4/week to 5.1, 5.8, and 5.1 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Soiling decreased in all from a mean of 5.5/week to 0.6, 0.1, and 1 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Laxative use decreased from a mean of 4.1 days/week to 0.6, 0.3, and 0.7 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Twenty-seven of 30 parents ranked their satisfaction a mean of 2.2 (range 1-excellent to 3-good). There were no significant differences in outcomes between the laboratory alone group and the laboratory plus home group. Biofeedback is beneficial for some children with chronic constipation and dyssynergic defecation. Supplemental home biofeedback does not improve long-term outcomes.", "Simple, incentive based behaviour modification, with or without a modest programme of psychotherapy involving outpatient visits every four to six weeks, seems to be associated with a useful cure rate in children with lower bowel function disorders. Appreciable social disadvantage seems to be the most important factor mitigating against a successful outcome, associated with non-compliance with treatment. Failure to respond to treatment was associated with important psychological problems. These were more common in the socially disadvantaged groups. Children from satisfactory social backgrounds who have lower bowl disturbances can be effectively treated by fairly simple programmes. More elaborate and expensive strategies should be reserved for those whose psychosocial circumstances make it possible to predict a less satisfactory outcome.", "Paradoxical external anal sphincter contraction during attempted defecation (anismus) is thought to be an important contributor to chronic faecal retention and encopresis in children. Biofeedback training can be used to teach children to abolish this abnormal contraction.\n A randomised controlled trial in medical treatment resistant and/or treatment dependent children with anismus using surface electromyographic (EMG) biofeedback training to determine whether such training produces sustained faecal continence. Up to four sessions of biofeedback training were conducted at weekly intervals for each patient. Anorectal manometry was performed before randomisation and six months later. Parents of patients completed the \"child behaviour checklist\" (CBCL) before randomisation and at follow up.\n Sixty eight children underwent anorectal manometry and EMG. Of these, 29 had anismus (ages 4-14 years) and were randomised to either EMG biofeedback training and conventional medical treatment (BFT) (n = 14) or to conventional medical treatment alone (n = 15). All but one child were able to learn relaxation of the external anal sphincter on attempted defecation. At six months' follow up, laxative free remission had been sustained in two of 14 patients in the BFT group and in two of 15 controls (95% confidence interval (CI) on difference, -24% to 26%). Remission or improvement occurred in four of 14 patients in the BFT group and six of 15 controls (95% CI on difference, -46% to 23%). Of subjects available for repeat anorectal manometry and EMG at six months, six of 13 in the BFT group still demonstrated anismus v 11 of 13 controls (95% CI on difference, -75% to -1%). Of the four patients in full remission at six months, only one (in the BFT group) did not exhibit anismus. Rectal hyposensitivity was not associated with remission or improvement in either of the groups. Mean CBCL total behaviour problem scores were not significantly different between the BFT and control groups, but there was a significant improvement in CBCL school scale scores in the BFT group, and this improvement was significantly greater than that seen in the control group.\n The result of this study, together with those reported in other controlled trials, argues against using biofeedback training in children with encopresis.", "In order to evaluate the efficacy of biofeedback for childhood encopresis, 50 children with encopresis were prospectively studied and randomized to receive biofeedback (B) or mineral oil therapy (M). Specificity of biofeedback was also evaluated by comparing outcomes of both regimens in children with normal (n = 32) and abnormal (n = 18) defecation patterns. Using a single blinded design, there were no significant differences in clinical outcomes between the 24 children receiving B and the 26 children receiving M at 3, 6, and 12 months. However, at 12 months six of nine children with abnormal defecation patterns were in remission or markedly improved after receiving B, compared to only three of nine children receiving M. In contrast, children with normal patterns appeared to respond better to M than did those receiving B (71 vs. 40% at 12 months). Biofeedback appears to warrant further evaluation in children with encopresis and abnormal defecation patterns.", "Chronic constipation is a common disorder in childhood. The underlying mechanisms responsible for chronic constipation remain unknown. Conventional methods of treatment often fail to produce satisfactory results. Favorable effects of biofeedback treatment for constipation have been suggested, however, with variable results reported in the literature. The main aim of the study was to evaluate biofeedback versus conventional therapeutic protocol in the treatment of chronic constipation over a short period of time (3 months). Forty-nine children with chronic idiopathic constipation, 24 allocated to conventional and 25 to biofeedback therapy were included in the study. Thorough history data on bowel function and symptoms, anorectal status and manometric testing were collected before and after treatment. Follow up consisted of a structured interview. Mean age was 94 and 92 months in the children treated by the conventional and biofeedback method, respectively. The initial prevalence of abnormal defecation dynamics was 58% and 56% in the group children allocated to conventional and biofeedback therapy, respectively. The difference was not statistically significant. After the treatment, the values of rectal sensation threshold, critical volume, and recto-anal inhibitory reflex volume were significantly higher, and the prevalence of abnormal defecation dynamics was significantly lower in the group on biofeedback therapy. Biofeedback is an effective method of treatment for chronic constipation in children in short term. Therapeutic results are especially favorable in the recovery of abnormal anorectal dynamics and manometric parameters. There is no clear evidence for long-term benefits of biofeedback therapy.", "Because abnormal defaecation dynamics, which can be modified by biofeedback, are considered to be the underlying problem in constipation, biofeedback training may be a useful treatment for constipation. This treatment has mainly been studied in uncontrolled trials. We evaluated defaecation dynamics and clinical outcome in chronically constipated children in a randomised study comparing conventional treatment and conventional treatment with biofeedback training.\n Patients, 5 to 16 years old, were referred to the Academic Medical Center in Amsterdam by general practitioners, school doctors, paediatricians, and psychiatrists. They had to fulfil at least two of four criteria for paediatric constipation and were included if they had been treated medically for at least one month before randomisation. Patients had a medical history, abdominal and rectal examination, and anorectal manometry at the start and end of the 6-week intervention period. The conventional group received laxative treatment with additional dietary advice, toilet training, and maintenance of a diary of bowel habits. The biofeedback group received the same conventional treatment and additionally five biofeedback training sessions. During the first 3 weeks, patients visited the outpatient clinic weekly; two subsequent visits were twice monthly.\n 94 patients were randomised to conventional treatment (CT) and 98 to conventional treatment with additional biofeedback training (CT+BF). Normal defaecation dynamics increased in the CT group from 41% to 52% (not significant) and in the CT+BF group from 38% to 86% (p = 0.001). At 6 weeks, more patients in the CT+BF group showed normal defaecation dynamics, compared to the CT group (p < 0.001). This result was unaltered by controlling for baseline status in a logistic regression model. At 1 year, successful treatment (defaecation frequency > or = 3/week, soiling and/or encopresis < 2/month, and no laxatives) was accomplished in 59% of the CT and 50% of the CT+BF group (p = 0.24). The results were maintained after 1 1/2 years follow-up. No association was found between achievement of normal defaecation dynamics and clinical outcome.\n Additional biofeedback training compared to conventional therapy did not result in higher success rates in chronically constipated children. Furthermore, achievement of normal defaecation dynamics was not associated with success: abnormal defaecation dynamics seem not to play a crucial role in the pathogenesis of childhood constipation. Intensive conventional laxative treatment should remain the first choice in chronically constipated children.", "To evaluate biofeedback training in children with encopresis and the effect on psychosocial function.\n Prospective controlled randomised study. PATIENT INTERVENTIONS: A multimodal treatment of six weeks. Children were randomised into two groups. Each group received dietary and toilet advice, enemas, oral laxatives, and anorectal manometry. One group also received five biofeedback training sessions.\n Successful treatment was defined as less than two episodes of encopresis, regular bowel movements, and no laxatives. Psychosocial function after treatment was assessed using the Child Behaviour Checklist.\n Children given laxatives and biofeedback training had higher success rates than those who received laxatives alone (39% v 19%) at the end of the intervention period. At 12 and 18 months, however, approximately 50% of children in each group were successfully treated. Abnormal behaviour scores were initially observed in 35% of children. Most children had improved behaviour scores six months after treatment. Children with an initial abnormal behaviour score who were successfully treated had a significant improvement in their behavioural profiles.\n Biofeedback training had no additional effect on the success rate or behaviour scores. Psychosocial problems are present in a subgroup of children with encopresis. The relation between successful treatment and improvement in behavioural function supports the idea that encopresis has an aetiological role in the occurrence and maintenance of behavioural problems in children with encopresis.", "About 2/3 of constipated children present anal-rectal dyssynergy (ARD) with paradoxical contraction of the external anal sphincter (EAS) during defecation.\n The aim of our study was to answer the question whether additional treatment with biofeedback training (BF) is more effective than traditional treatment. MATERIALS, METHODS: We assessed chronically constipated children who fulfilled the criteria of ARD: recto-sigmoid transit time in Hinton's test with radio-paque markers at least 28.8 h, paradoxical EAS contraction during defecation trials (anorectal manometry). The study included 22 constipated children (16 boys and 6 girls), aged 5 to 14 years (mean 8.1 +/- SD 2.8). Children were randomly divided in two groups. In group I at the start of the study children had four day-by-day sessions of BF training based on the anorectal manometry and the surface EMG. Children from group II received only traditional treatment. The follow-up was 6 months. Improvement was estimated based on manometric data, number and quality of stools.\n In the group I after one month, more manometric parameters, significantly improved as compared to the II group. During the observation period the number of stools increased and their quality improved in both groups. There was no statistically significant difference between the groups in terms of the above mentioned symptoms.\n Treatment with BF can improve rectal sensation and particularly defecation dynamics, faster than the traditional method. There is no significant effect of additional BF treatment on such objective symptoms as the number and quality of stools.", "Primary faecal incontinence (encopresis) in children is usually treated with laxative medication and a behaviour modification programme aimed at promoting regular toileting, but the effectiveness of laxatives has never been adequately investigated. 169 children with encopresis and evidence of stool on plain abdominal radiograph were randomly allocated to receive multimodal (MM) therapy (laxatives plus behaviour modification; n = 83) or behaviour modification alone (BM; n = 86). Mean (SD) follow-up was 55.1 (27.0) weeks and 56.7 (32.0) weeks, respectively. By 12 months' follow-up 42 (51%) of the MM group and 31 (36%) of the BM group (p = 0.079) had achieved remission (at least one 4 week period with no soiling episodes) and 52 (63%) vs 37 (43%) (p = 0.016) had achieved at least partial remission (soiling no more than once a week). MM subjects achieved remission significantly sooner than BM subjects, and the difference in the Kaplan-Meier remission curves was most striking in the first 30 weeks of follow-up (p = 0.012). The patterns of compliance with toileting in the treatment groups were almost identical, although about 1 in 8 children overall did not comply with the sitting programme. After exclusion of the 24 poor compliers, there was no significant difference between BM and MM groups. This study shows a clear advantage overall for the use of laxative medication, although the benefit may not be as great for children who are able to maintain regular toileting.", "This study evaluated the benefits of enhanced toilet training delivered through the Internet for children with encopresis. Twenty-four children with encopresis were randomly assigned to the Internet intervention group (Web) or no Internet intervention group (No-Web). All participants continued to receive routine care from their primary care physician. The Web participants demonstrated greater improvements in terms of reduced fecal soiling, increased defecation in the toilet, and increased unprompted trips to the toilet (ps<.02). Both groups demonstrated similar improvements in knowledge and toileting behaviors. Internet interventions may be an effective way of delivering sophisticated behavioral interventions to a large and dispersed population in a convenient format.", "To determine whether outcome in chronically constipated and encopretic children with abnormal defecation dynamics could be improved with biofeedback training, we randomly assigned patients, 5 to 16 years of age, to receive conventional treatment alone (n = 19) or conventional plus biofeedback treatment (n = 22) and evaluated physiologic outcome at 7 months and clinical outcome at 7 and 12 months. Eighty-six percent of patients learned normal defecation dynamics with up to six biofeedback sessions. At 7 months, 13% of conventionally treated and 77% of biofeedback-treated patients had normal defecation dynamics (p less than 0.01); one conventionally treated (5%) and 12 biofeedback-treated patients (55%) had recovered (p less than 0.01). Learning normal defecation dynamics was correlated with clinical recovery (p less than 0.01). At 7 months, 11% of patients with normal defecation dynamics after biofeedback treatment had abnormal defecation dynamics, and 71% of the biofeedback-treated patients with normal defecation dynamics recovered. At 12 months, 16% of conventionally treated and 50% of biofeedback-treated patients had recovered (p less than 0.05). Balloon defecation did not improve significantly in those who learned normal defecation dynamics. Therefore the ability to defecate balloons is apparently not dependent on the normal function of the external and sphincter and pelvic floor muscles alone. Biofeedback treatment is complementary to a good conventional therapeutic regimen in patients with abnormal defecation dynamics.", "A double-blind randomly controlled trial of one particular laxative, Senokot, used in moderate dosage, was carried out on a group of 40 children with severe and persistent soiling and often with a history of faecal retention. Significant improvement occurred following three months of outpatient treatment using a behavioural approach and either Senokot, placebo or no medication. However, there was no evidence either during the trial or subsequently when Senokot was employed to supplement behavioural treatment in every child who continued with therapy that this laxative contributed in any way to relieving the problem in this group of cases." ]

[ "11524188", "10216048", "12648639", "12353900" ]

[ "Necessity of vitrectomy when optic capture is performed in children older than 5 years.", "Randomised clinical trial of lensectomy versus lens aspiration and primary capsulotomy for children with bilateral cataract in south India.", "Morphological and functional results of AcrySof intraocular lens implantation in children: prospective randomized study of age-related surgical management.", "Posterior continuous curvilinear capsulorhexis with and without optic capture of the posterior chamber intraocular lens in the absence of vitrectomy." ]

[ "To determine whether anterior vitrectomy is necessary when optic capture is performed in children between 5 and 12 years old with congenital cataract.\n Iladevi Cataract and IOL Research Center, Ahmedabad, India.\n This prospective randomized controlled study comprised 41 eyes of 25 children whose mean age was 83.57 months (range 60 to 144 months). Intraocular lens (IOL) implantation with optic capture through a primary posterior continuous curvilinear capsulorhexis was performed in all the eyes. The IOL haptics were bag fixated. Patients were randomly assigned to 1 of 2 groups. Vitrectomy was performed in 1 group (n = 21 eyes) and not performed in the other group (n = 20 eyes). The mean follow-up was 21.04 months. A Student t test and chi-square test were used for statistical analysis.\n All eyes in the vitrectomy group and 30% in the no-vitrectomy group had a clear visual axis at the last follow-up (P <.001) The visual axis was obscured as a result of anterior vitreous fibrosis in 70% of eyes in the no-vitrectomy group. High-contrast visual acuity was not significantly different between groups (P =.28). Low-contrast sensitivity was significantly better in the vitrectomy group (P =.02). Eighteen eyes (85.7%) in the vitrectomy group and 16 eyes (80%) in the no-vitrectomy group developed deposits on the IOL (P =.62). The deposits were present at the last follow-up in 4 eyes (19.0%) in the vitrectomy group and in 6 eyes (30.0%) in the no-vitrectomy group (P =.85). Three eyes (14.3%) in the vitrectomy group and 8 eyes (40.0%) in the no-vitrectomy group developed synechias (P =.06).\n The results suggest that anterior vitrectomy is necessary with optic capture in children with congenital cataract who are between 5 and 12 years old.", "The primary objective was to determine which surgical technique gave the best long term visual outcome for infants and young children with bilateral symmetrical cataract in south India. Secondary objectives were to assess complications and the need for further surgical intervention.\n A randomised controlled clinical trial was undertaken. 65 children under 10 years old with bilateral cataract had one eye treated by lensectomy and the other by aspiration with primary capsulotomy.\n 56 children (86%) with a mean age at surgery of 53 months were reviewed 3 years after surgery. The overall binocular acuity was 6/18 or better in 57.1% and 6/60 or better in 94.6%. There was no difference in visual acuity between the matched pairs of eyes undergoing aspiration or lensectomy at the third year of follow up (p=0.57). Aspiration eyes were more likely to require a secondary procedure to restore vision than lensectomy eyes (66.1% v 1.8%).\n Aspiration with primary capsulotomy gives an acceptable visual outcome in this part of India providing that there is good follow up to manage capsule opacification. If secondary intervention is not possible owing to poor compliance with follow up, then lensectomy is likely to give better long term visual rehabilitation providing there is good maintenance and technical support for the lensectomy equipment.", "To evaluate the prevalence and severity of posterior capsule opacification (PCO) in pediatric eyes with a foldable acrylic AcrySof (Alcon) intraocular lens (IOL) and age-related surgical methods.\n Department of Ophthalmology, University of Vienna, Medical School, Vienna, Austria.\n This prospective randomized study comprised 50 eyes of 34 children aged between 2 and 16 years. Eyes of children between 2 and 5.9 years were consecutively randomized to Group 1a (primary posterior capsulotomy and anterior vitrectomy) or Group 1b (optic capture in addition). Eyes of children between 6 and 16 years were consecutively randomized to Group 2a (primary posterior capsulotomy without anterior vitrectomy), Group 2b (optic capture in addition), or Group 2c (in-the-bag IOL implantation without opening the posterior capsule). Main outcome parameters were the incidence and severity of PCO formation, early postoperative complications, pigmented cell deposits on the IOL surface, and cataract morphology.\n The visual axis was clear at the last follow-up in all eyes in Groups 1a, 1b, 2a, and 2b except in 1 eye in Group 1a. Sixty-percent of eyes in Group 2c had PCO. The incidence of early postoperative complications was significantly higher in eyes that developed PCO than in those that maintained a clear visual axis. There was no evidence that cataract morphology influenced PCO rates.\n The AcrySof IOL was well tolerated in pediatric eyes. Optic capture was not necessary to ensure a clear visual axis. Primary posterior capsulotomy should be performed in preschool and uncooperative children and in eyes expected to have relatively high postoperative inflammation. Implanting the AcrySof in the bag and leaving the posterior capsule intact is acceptable for school children and juveniles with isolated developmental cataract.", "To evaluate the efficacy of posterior continuous curvilinear capsulorhexis (PCCC) with optic capture of the posterior chamber intraocular lens (PC IOL) in the absence of vitrectomy in preventing secondary opacification of the visual axis following pediatric cataract surgery.\n Thirty-four eyes of 28 children with congenital or developmental cataract, aged 1.5 to 12 years (mean, 6.39 years), were included in this prospective, randomized study. Anterior continuous curvilinear capsulorhexis (ACCC) with PCCC without optic capture of the PC IOL was performed in group A (18 eyes) and ACCC with PCCC with optic capture of the PC IOL was performed in group B (16 eyes). None of the eyes underwent anterior vitrectomy. Secondary opacification of the visual axis, visual acuity, and possible complications were observed and analyzed.\n The follow-up period ranged from 8 to 28 months (mean, 17.5 months). All 16 eyes (100%) in group B had a clear visual axis at the end of follow-up. Eight eyes (44.4%) in group A had significant opacification of the visual axis. The difference between the two groups was statistically significant (P = .0011). No eye in group B required secondary intervention, whereas all 8 eyes in group A with significant secondary opacification required secondary intervention. There was no statistically significant difference in other complications such as anterior chamber reaction, fibrin formation, lenticular precipitates, and posterior synechiae. The final best-corrected visual acuity at the end of follow-up was comparable in the two groups (P > .05).\n PCCC with optic capture of the PC IOL prevents secondary opacification of the visual axis even in the absence of vitrectomy." ]

[ "8464671", "9372670" ]

[ "Failure of cromolyn sodium to reduce the incidence of bronchopulmonary dysplasia: a pilot study. The Neonatal Cromolyn Study Group.", "Cromolyn sodium prophylaxis inhibits pulmonary proinflammatory cytokines in infants at high risk for bronchopulmonary dysplasia." ]

[ "This prospective, randomized, blinded clinical trial was conducted to test whether therapy with cromolyn sodium might decrease the incidence or severity of bronchopulmonary dysplasia when given to newborns with respiratory distress syndrome. Cromolyn (20 mg) or placebo was aerosolized to intubated newborns with respiratory distress syndrome every 6 hours, beginning on the first day of intubation. Patients were stratified by birth weight less than 1000 g and 1000 to 2000 g; primary outcome success was defined as survival to 30 days without oxygen dependence. Of 10 patients enrolled who were less than 1000 g birth weight, there were no treatment successes, preventing outcome analysis. The study was discontinued after 28 patients of 1000 to 2000 g birth weight had been studied, at which time it had been found with 95% confidence, with a power of .80, that cromolyn sodium did not decrease by 50% the incidence of bronchopulmonary dysplasia. Severity of bronchopulmonary dysplasia was also similar, with 4 patients in the treatment group and 3 in the placebo group receiving mechanical ventilation at 30 days. Possible reasons for this study outcome include (1) a delivered dose too small to produce a clinical effect; (2) the start of therapy too late to prevent the onset of inflammation; (3) inadequate effect of cromolyn on polymorphonuclear cells in vivo; or (4) development of bronchopulmonary dysplasia through factors unaffected by the actions of cromolyn.", "An imbalance of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and the neutrophil chemotactic factor IL-8 and inhibitors (e.g., soluble TNF receptors and IL-1ra) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia (BPD). Disodium cromoglycate (DSCG) has anti-inflammatory effects in asthma, a disease with many similarities with BPD. In a prospective, randomized, blinded study, we examined whether early DSCG therapy inhibits proinflammatory cytokines in infants at risk for BPD. Twenty-six infants who were identified as high risk (> or = 75% probability) for oxygen-dependency at 28 d by a 12-h predictive score and survived 48 h were randomized to nebulized DSCG 20 mg (n = 13) or 2 cc NS (control, n = 13) every 6 h from Day 3 to Day 28. Lung lavage was collected on Day 3 (pre-study) and Day 7 and analyzed for cell count and differential and TNF-alpha, sTNFR1, sTNFR2, IL-1 beta, IL-1ra, and IL-8 concentrations. The groups' pre-study lavage cytokine concentrations were similar, but TNF-alpha and IL-8 concentrations were 3.6- and 4.9-fold lower in the DSCG group on Day 7 compared with levels in the control group. Soluble TNF receptors were unaffected by DSCG. There was a trend towards lower IL-1 beta levels in DSCG-treated infants on Day 7, but IL-1ra levels were unaffected by DSCG therapy. Three control subjects, but no DSCG-treated infants, died during the study period (p = 0.07). There were no significant differences between survivors of the two groups for oxygen-dependency at 28 d (100% control subjects; 85% DSCG). These results suggest that nebulized DSCG may exert an anti-inflammatory effect in the lungs of infants < or = 1,000 g at risk for BPD." ]

[ "17227907", "11984098", "18359433", "18065731", "11145492", "9469333", "8270972", "16192581", "16509835", "10819701", "16139656", "11896107", "15750359" ]

[ "Randomized, double-blind, placebo-controlled crossover trials of venlafaxine for hot flashes after breast cancer.", "A pilot study of magnetic therapy for hot flashes after breast cancer.", "A randomized controlled trial of relaxation training to reduce hot flashes in women with primary breast cancer.", "Randomized, controlled trial of acupuncture for the treatment of hot flashes in breast cancer patients.", "Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial.", "Prospective evaluation of vitamin E for hot flashes in breast cancer survivors.", "Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.", "Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial.", "Randomized, double-blind, placebo-controlled, crossover study of sertraline (Zoloft) for the treatment of hot flashes in women with early stage breast cancer taking tamoxifen.", "Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study.", "Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial.", "Phase III evaluation of fluoxetine for treatment of hot flashes.", "A pilot, randomized, double-blinded, placebo-controlled trial of individualized homeopathy for symptoms of estrogen withdrawal in breast-cancer survivors." ]

[ "Although venlafaxine reduces self-reported hot flashes, no data have established the drug's impact on physiologically documented hot flashes. Two randomized, double-blind, placebo-controlled crossover trials examined the efficacy of two doses of venlafaxine in relation to physiological and self-reported hot flashes and other outcomes, including negative affect, fatigue, sleep, and quality of life.\n Sample: 57 breast cancer survivors in the low-dose study; 20 in the high-dose study. Setting: university cancer clinics in the Southeast and Midwest. Intervention: 37.5 mg of venlafaxine (low-dose study) or 75 mg of venlafaxine (high-dose study). Measures: hot flash frequency (physiological monitor, diary, and event marker), hot flash severity (diary), hot flash bother (diary), and questionnaires for hot flash impact on daily life, negative affect, fatigue, sleep, and quality of life.\n Subjective but not physiological hot flash measures showed placebo effects. Venlafaxine resulted in modest decreases in hot flashes, but only hot flash interference improved differentially at the higher dose. The timing of venlafaxine's effects on hot flashes varied by dose. Only women with a > or =50% decrease in physiological hot flashes experienced significant improvement in fatigue, sleep quality, and quality of life. Although side effects were mild, most patients discontinued venlafaxine long-term.\n Although venlafaxine resulted in modest and acute reductions in hot flashes with few side effects, it may not be tolerable to some patients long-term. At least 50% relief in physiological hot flashes may be needed for patients to demonstrate improvement in other outcomes, including decreased fatigue, improved sleep, and improved quality of life.", "The purpose of this randomized placebo-controlled crossover pilot study was to evaluate the effectiveness and acceptability of magnetic therapy for hot flashes among breast cancer survivors. Participants completed a 24-hour baseline hot-flash monitoring session, wore the magnetic devices or placebo for 3 days, completed an after-treatment hot-flash monitoring session, experienced a 10-day washout period, and then crossed over to the opposite study arm. Magnetic devices and placebos were placed on 6 acupressure sites corresponding to hot-flash relief. Complete data were available from 11 survivors of breast cancer. Results indicated magnetic therapy was no more effective than placebo in decreasing hot-flash severity, and contrary to expectations, placebo was significantly more effective than magnets in decreasing hot-flash frequency, bother, interference with daily activities, and overall quality of life. Implications for clinical practice and future research include the need to explore alternative interventions aimed at alleviating hot flashes in this population.", "Hot flashes are experienced by about 52% of perimenopausal women. After breast cancer, this may increase to 70%. The use of hormone replacement therapy is not recommended in women who have had breast cancer; therefore, alternatives are required to help relieve hot flashes. This study was conducted to assess the efficacy of relaxation training in reducing the incidence of hot flashes in women with primary breast cancer. This was a randomized controlled trial of 150 women with primary breast cancer who experienced hot flashes. The intervention group received a single relaxation training session and was instructed to use practice tapes on a daily basis at home for one month; the control group received no intervention. Outcomes were incidence and severity of flashes using a diary and validated measures of anxiety and quality of life. The incidence and severity of hot flashes, as recorded by diaries, each significantly declined over one month (P<0.001 and P=0.01, respectively), compared with the control group. Distress caused by flashes also significantly declined in the treatment group over one month (P=0.01), compared with the control group. There were no significant differences between the treatment group and the control group at three months and no changes in anxiety or quality-of-life measures. Relaxation may be a useful component of a program of measures to relieve hot flashes in women with primary breast cancer.", "To determine the immediate and long-term effects of true acupuncture versus sham acupuncture on hot flash frequency in women with breast cancer.\n Seventy-two women with breast cancer experiencing three or more hot flashes per day were randomly assigned to receive either true or sham acupuncture. Interventions were given twice weekly for 4 consecutive weeks. Hot flash frequency was evaluated at baseline, at 6 weeks, and at 6 months after initiation of treatment. Patients initially randomly assigned to the sham group were crossed over to true acupuncture starting at week 7.\n The mean number of hot flashes per day was reduced from 8.7 (standard deviation [SD], 3.9) to 6.2 (SD, 4.2) in the true acupuncture group and from 10.0 (SD, 6.1) to 7.6 (SD, 5.7) in the sham group. True acupuncture was associated with 0.8 fewer hot flashes per day than sham at 6 weeks, but the difference did not reach statistical significance (95% CI, -0.7 to 2.4; P = .3). When participants in the sham acupuncture group were crossed over to true acupuncture, a further reduction in the frequency of hot flashes was seen. This reduction in hot flash frequency persisted for up to 6 months after the completion of treatment.\n Hot flash frequency in breast cancer patients was reduced following acupuncture. However, when compared with sham acupuncture, the reduction by the acupuncture regimen as provided in the current study did not reach statistical significance. We cannot exclude the possibility that a longer and more intense acupuncture intervention could produce a larger reduction of these symptoms.", "Hot flashes can be troublesome, especially when hormonal therapy is contraindicated. Preliminary data have suggested that newer antidepressants, such as venlafaxine, can diminish hot flashes. We undertook a double-blind, placebo-controlled, randomised trial to assess the efficacy of venlafaxine in women with a history of breast cancer or reluctance to take hormonal treatment because of fear of breast cancer.\n Participants were assigned placebo (n=56) or venlafaxine 37.5 mg daily (n=56), 75 mg daily (n=55), or 150 mg daily (n=54). After a baseline assessment week, patients took the study medication for 4 weeks. All venlafaxine treatment started at 37.5 mg daily and gradually increased in the 75 mg and 150 mg groups. Patients completed daily hot-flash questionnaire diaries. The primary endpoint was average daily hot-flash activity (number of flashes and a score combining number and severity). Analyses were based on the women who provided data throughout the baseline and study weeks.\n 191 patients had evaluable data for the whole study period (50 placebo, 49 venlafaxine 37.5 mg, 43 venlafaxine 75 mg, 49 venlafaxine 150 mg). After week 4 of treatment, median hot flash scores were reduced from baseline by 27% (95% CI 11-34), 37% (26-54), 61% (50-68), and 61% (48-75) in the four groups. Frequencies of some side-effects (mouth dryness, decreased appetite, nausea, and constipation) were significantly higher in the venlafaxine 75 mg and 150 mg groups than in the placebo group.\n Venlafaxine is an effective non-hormonal treatment for hot flashes, though the efficacy must be balanced against the drug's side-effects. Confirmation of the results of this 4-week study awaits the completion of three ongoing randomised studies to assess the effects of other related antidepressants for the treatment of hot flashes.", "Hot flashes represent a substantial clinical problem for some breast cancer survivors. Although estrogen or progesterone preparations can alleviate these symptoms in many patients, concern remains regarding the use of hormonal preparations in such women. Thus, there is a perceived need for nonhormonal treatments for hot flashes for breast cancer survivors. Based on anecdotal evidence that vitamin E was helpful, we designed a trial to investigate this matter.\n We developed and conducted a placebo-controlled, randomized, crossover trial where, after a 1 week baseline period, patients received 4 weeks of vitamin E 800 IU daily, then 4 weeks of an identical-appearing placebo, or vice versa. Diaries were used to measure potential toxicities and hot flashes during the baseline week and the two subsequent 4-week treatment periods.\n The 120 patients evaluated for toxicity failed to show any. The 105 patients who finished the first treatment period showed a similar reduction in hot flash frequencies (25% v 22%; P = .90) for the two study arms. A crossover analysis, however, showed that vitamin E was associated with a minimal decrease in hot flashes (one less hot flash per day than was seen with a placebo) (P < or = .05). At the study end, patients did not prefer vitamin E over the placebo (32% v 29%, respectively).\n Although this trial was able to show a statistically significant hot flash reduction with vitamin E compared to a placebo, the clinical magnitude of this reduction was marginal.", "To determine the efficacy of transdermal clonidine for alleviating tamoxifen-induced hot flashes in women with a history of breast cancer.\n A randomized, double-blind, crossover design was used in this prospective study. Women with a history of breast cancer who were receiving tamoxifen and suffering from hot flashes were potentially eligible for this protocol study.\n Clonidine did reduce hot-flash frequency to a degree that was statistically impressive (P < .0001), but clinically moderate (20% reduction from baseline). It also decreased hot-flash severity (P = .02, 10% reduction from baseline). Clonidine was related to increased mouth dryness (P < .001), constipation (P < .02), itchiness under the patch (P < .01), and drowsiness (P < .05).\n Better means are needed to alleviate hot flashes among patients in whom estrogen therapy is contraindicated.", "In an open-label trial we have previously demonstrated that paroxetine reduces hot flashes. We initiated a stratified, randomized, double-blind, cross-over, placebo-controlled trial to investigate the efficacy of paroxetine 10 mg and 20 mg compared to placebo in reducing hot flash frequency and composite score. A secondary objective was to evaluate quality of life (QOL) parameters.\n Women who suffered at least two hot flashes a day for 1 month or longer were eligible. Women were randomly assigned to 4 weeks of paroxetine 10 mg or 20 mg followed by placebo for 4 weeks, or placebo for 4 weeks followed by paroxetine 10 mg or 20 mg for 4 weeks. Participants completed baseline daily hot flash diaries for one week prior to the start of the study and throughout the study, and QOL questionnaires at baseline, week 5 and week 9.\n 279 women were screened, and 151 were randomly assigned. Paroxetine 10 mg reduced hot flash frequency and composite score by 40.6% and 45.6%, respectively, compared to 13.7% and 13.7% for placebo (P = .0006 and P = .0008, respectively). Paroxetine 20 mg reduced hot flash frequency and composite score by 51.7% and 56.1%, respectively, compared with 26.6% and 28.8% for placebo (P = .002 and P = .004, respectively). Efficacy was similar between the two doses, but women were less likely to discontinue low-dose paroxetine. Paroxetine 10 mg was associated with a significant improvement in sleep compared with placebo (P = .01).\n Paroxetine is an effective treatment for hot flashes in women with or without a prior breast cancer.", "We observed the relief of hot flashes in breast cancer survivors taking tamoxifen and treated with sertraline for depression. Our objective was to assess the effect of sertraline on the frequency and severity of hot flashes, mood status, and health-related quality of life. We used a randomized, double-blind, placebo-controlled, crossover study using 6 weeks of sertraline (50 mg each morning) versus placebo. Study participants were 62 breast cancer survivors from an oncology clinic in a tertiary care center on adjuvant tamoxifen reporting bothersome hot flashes. Patients were asked to keep a daily hot flash diary to record hot flash frequency and severity, from which hot flash scores (frequency x severity) were calculated. The Center for Epidemiologic Studies depression scale and Functional Assessment of Cancer Therapy--Breast (FACT-B) (at baseline, 6 weeks, and 12 weeks) were used to assess mood and quality of life. Sixty-two women were accrued. Forty-seven women (median age 53.9 years, range 36.6-77.1 years; 89% postmenopausal; 85.5% Caucasian) completed the first 6 weeks and 39 completed 12 weeks. The baseline daily hot flash frequency and score were 5.8 (standard deviation 4.1) and 11.5 (14.0), respectively. At the end of the first 6 weeks, hot flash frequency decreased by 50% in 36% of those taking sertraline compared to 27% taking placebo. In the crossover analysis, sertraline was significantly more effective than placebo: women crossing from placebo to sertraline had a decrease (-0.9 and -1.7) in hot flash frequency and score, whereas those crossing from sertraline to placebo had an increase (1.5 and 3.4) in hot flash frequency and score (p = 0.03 and 0.03). Forty-eight percent preferred the sertraline period, 11% preferred the placebo period, and 41% had no preference (p = 0.006). Measures of depression and quality of life were within normal range and did not change significantly within treatment groups. Sertraline decreases hot flashes in breast cancer survivors taking tamoxifen and women prefer sertraline to placebo. Further study of sertraline for the management of hot flashes is warranted.", "Hot flashes are the most frequently reported side effect of tamoxifen treatment. Although hormones are an effective treatment, their safety is questionable in women with breast cancer. It is therefore important to evaluate nonhormonal treatments for hot flashes.\n To evaluate the effectiveness of oral clonidine for control of hot flashes associated with tamoxifen therapy in postmenopausal women with breast cancer.\n Randomized, double-blind, placebo-controlled clinical trial.\n University of Rochester Cancer Center Community Clinical Oncology Program.\n 194 postmenopausal women with breast cancer who were receiving adjuvant tamoxifen therapy.\n Oral clonidine hydrochloride, 0.1 mg/d, or placebo for 8 weeks.\n In a daily diary, patients recorded number, duration, and severity of hot flashes and overall quality-of-life score (on a 10-point scale) during a 1-week baseline period and during the 4th, 8th, and 12th weeks of the study.\n Patients in the placebo and treatment groups were similar in age, duration of tamoxifen use, reported frequency and duration of hot flashes at baseline, and dropout rates. One hundred forty-nine patients completed 12 weeks of follow-up. The mean decrease in hot flash frequency was greater in the clonidine group than in the placebo group after 4 weeks of treatment (37% compared with 20% [95% CI for difference, 7% to 27%]) and 8 weeks of treatment (38% compared with 24% [CI for difference, 3% to 27%]). Patients receiving clonidine were more likely than patients receiving placebo to report difficulty sleeping (41% compared with 21%; P = 0.02). A significant difference was seen in the mean change in quality-of-life scores (0.3 points in the clonidine group compared with -0.2 points in the placebo group; P = 0.02) at 8 weeks, although the median difference was 0 in both groups.\n Oral clonidine, 0.1 mg/d, is effective against tamoxifen-induced hot flashes in postmenopausal women with breast cancer.", "Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer.\n 420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat.\n Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity.\n Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer.", "Hot flashes can be a prominent problem in women with a history of breast cancer. Given concerns regarding the use of hormonal therapies in such patients, other nonhormonal means for treating hot flashes are required. Based on anecdotal information regarding the efficacy of fluoxetine and other newer antidepressants for treating hot flashes, the present trial was developed.\n This trial used a double-blinded, randomized, two-period (4 weeks per period), cross-over methodology to study the efficacy of fluoxetine (20 mg/d) for treating hot flashes in women with a history of breast cancer or a concern regarding the use of estrogen (because of breast cancer risk). Eligible patients had to have reported that they averaged at least 14 hot flashes per week; they could have received tamoxifen or raloxifene as long as they were on a stable dose. The major outcome measure was a bivariate construct representing hot flash frequency and hot flash score, analyzed by a classic sums and differences cross-over analysis.\n Eighty-one randomized women began protocol therapy. By the end of the first treatment period, hot flash scores (frequency x average severity) decreased 50% in the fluoxetine arm versus 36% in the placebo arm. Cross-over analysis demonstrated a significantly greater marked hot flash score improvement with fluoxetine than placebo (P =.02). The results were not adjusted for potential confounding influences, including age and tamoxifen use. The fluoxetine was well tolerated.\n This dose of fluoxetine resulted in a modest improvement in hot flashes.", "To pilot an investigation of individualized homeopathy for symptoms of estrogen withdrawal in breast cancer survivors.\n Randomized, double-blinded, placebo-controlled trial.\n Outpatient department of a National Health Service (NHS) homeopathic hospital.\n Fifty-seven (57) women met inclusion criteria and 53 were randomized to the study.\n After 2 weeks of baseline assessment, all participants received a consultation plus either oral homeopathic medicine or placebo, assessed every 4 weeks for 16 weeks.\n The primary outcome measures were the activity score and profile score of the Measure Yourself Medical Outcome Profile (MYMOP).\n Eighty-five percent (85%) (45/53) of women completed the study. There was no evidence of a difference seen between groups for either activity (adjusted difference =-0.4, 95% confidence interval CI -1.0 to 0.2, p = 0.17) or profile scores (adjusted difference = -0.4, 95% CI -0.9 to 0.1, p = 0.13) using this trial design, although post hoc power calculations suggests that 65-175 would be needed per group to detect differences of this magnitude with sufficient precision. Clinically relevant improvements in symptoms and mood disturbance were seen for both groups over the study period.\n Improvements were seen for symptom scores over the study period. However, presuming these improvements were caused by the individualized homeopathic approach, the study failed to show clearly that the specific effect of the remedy added further to the nonspecific effects of the consultation. Future trial design must ensure adequate power to account for the nonspecific impact of such complex individualized interventions while pragmatic designs may more readily answer questions of clinical and cost effectiveness." ]

[ "9892887", "11469160", "10473306", "8973231", "486361", "10088980", "462201", "9328501", "8829399", "12765500" ]

[ "Can midwives reduce postpartum psychological morbidity? A randomized trial.", "Effect of timing of critical incident stress debriefing (CISD) on posttraumatic symptoms.", "A randomized controlled trial of individual psychological debriefing for victims of violent crime.", "A randomised controlled trial of psychological debriefing for victims of road traffic accidents.", "Crisis intervention: an experimental study of the effects of a brief period of counselling on the anxiety of relatives of seriously injured or ill hospital patients.", "PTSD in ambulant RTA victims: a randomized controlled trial of debriefing.", "An experimental evaluation of crisis intervention.", "Randomised controlled trial of psychological debriefing for victims of acute burn trauma.", "The influence of psychological debriefing on emotional adaptation in women following early miscarriage: a preliminary study.", "Stress debriefing after childbirth: a randomised controlled trial." ]

[ "Women who are traumatized after childbirth find that listening, support, counseling, understanding, and explanation are the most useful treatments. However, little evidence is available from randomized trials of the relative efficacy of these treatments as a positive postnatal intervention. This study purpose was to examine if postnatal \"debriefing\" by midwives can reduce psychological morbidity after childbirth.\n A randomized trial was conducted in a regional teaching hospital in northwest England. One hundred and twenty postnatal primigravidas were allocated by sealed envelopes to receive the debriefing intervention (n = 56) or not (n = 58). The main outcome measure was the Hospital Anxiety and Depression (HAD) scale administered by postal questionnaire 3 weeks after delivery. The proportion of women in each group with anxiety and depression scores of more than 10 points were compared, using odds ratios and 95% confidence intervals.\n Women who received the intervention were less likely to have high anxiety and depression scores after delivery when compared with the control group.\n The support, counseling, understanding, and explanation given to women by midwives in the postnatal period provides benefits to psychological well-being. Maternity units have a responsibility to develop a service that offers all women the option of attending a session to discuss their labor.", "Seventy-seven civilian employees who were victims of robbery were randomly assigned to either an immediate (< 10 hr) or delayed (> 48 hr) debriefing group, using the J. Mitchell (1983) CISD protocol. Scores on the Posttraumatic Stress Diagnostic Scale were obtained at 4 time intervals: debrief, 2 and 4 days post-debrief, and 2 weeks postrobbery. The number and severity of symptoms did not differ at debrief, but were lower for the immediate than for the delayed group at each subsequent time interval. The number and severity of symptoms declined across time intervals; however, although this reduction was pronounced for the immediate group it was minimal for the delayed group. The results supported use of immediate debriefing with this type of incident and victim.", "It has been suggested that giving people the opportunity talk about a traumatic experience may prevent the development of later disorder. We tested the efficacy of two brief interventions, education and psychological debriefing, designed to prevent adverse psychological reactions to criminal victimization.\n Individuals who had been the victims of a violent crime within the past month were written to and invited to take part in a study of their attitudes to crime and punishment: 2161 were contacted and 243 replied, of whom 157 were eligible and were randomly assigned either to an education condition, to a psychological debriefing plus education condition, or to an assessment only condition. Education involved providing information about normal post-traumatic reactions. Debriefing involved in-depth probing about events, thoughts and feelings experienced during the crime. Subjects were recruited from police and hospital sources and interviewed in their own homes: 138 were followed up at 6 months, and 92 at 11 months.\n Outcome was assessed using a DSM-III-R diagnosis of PTSD, the Post-traumatic Symptom Scale, the Impact of Event Scale and the Beck Depression Inventory. All groups improved over time but there were no between-group differences.\n No evidence was found to support the efficacy of brief one-session interventions for preventing post-traumatic symptoms in individual victims of violent crime.", "nan", "This study was designed to examine the effects of anxiety levels, as measured by the Gottschalk & Gleser (1969) and the Viney & Westbrook (1976) content analysis scales, of a brief period of supportive counselling of relatives who arrived at a hospital emergency admitting ward with a seriously ill or injured patient. Verbal samples were taken for analysis from the subjects before and after a period of counselling (or a period of no counselling for the control group). The results showed that the initial anxiety levels for subjects in both groups was very high. For both the psychoanalytically oriented Gottschalk & Gleser anxiety scale and the Viney & Westbrook scale of cognitive anxiety there was a decrease in the level of anxiety for the counselled group compared with the non-counselled group. The results showed that such crisis intervention in hospitals for relatives who accompany patients to the hospital can reduce their very high levels of diffuse and generalized anxiety.", "This report examines initial distress levels, course of symptoms, incidence of posttraumatic stress disorder (PTSD), predictors of short-term outcome, and value of prophylactic counseling in a consecutive series of 40 ambulant trauma clinic attenders with minor road traffic accident (RTA) injuries. Subjects were randomly allocated to intervention and monitoring groups following assessment at a mean of 7 days posttrauma and reassessed at 3 months using a variety of standard rating scales. Seventy-five percent reported significant levels of distress at 1 week posttrauma. By 3 months this had decreased sharply to 35%, and 22% were significantly impaired by clinical assessment. Incidence of PTSD over 3 months was estimated at 19% and point prevalence at 3 months posttrauma was 9%. High initial distress, increasing age, and high levels of perceived threat were significant independent predictors of morbidity, and no significant differences in outcome were found between intervention and monitoring groups at 3 months.", "nan", "Psychological debriefing (PD) is widely used following major traumatic events in an attempt to reduce psychological sequelae.\n One hundred and thirty-three adult burn trauma victims entered the study. After initial questionnaire completion, participants were randomly allocated to an individual/couple PD group or a control group who received no intervention; 110 (83%) were interviewed by an assessor blind to PD status three and 13 months later.\n Sixteen (26%) of the PD group had PTSD at 13-month follow-up, compared with four (9%) of the control group. The PD group had higher initial questionnaire scores and more severe dimensions of burn trauma than the control group, both of which were associated with a poorer outcome.\n This study seriously questions the wisdom of advocating one-off interventions post-trauma, and should stimulate research into more effective initiatives.", "About a fifth of pregnancies end in miscarriage, leading to emotional consequences, such as anxiety and depression, which may last for a number of months. Despite this, women are not routinely provided with follow-up care. Anecdotal evidence suggests that follow-up focusing on emotional experiences may have beneficial effects. This study tests the hypothesis that the psychological debriefing process has a positive influence on emotional adaptation. Women were assessed, using the Hospital Anxiety and Depression Scale and Impact of Events Scale, at one week and four months post-miscarriage. Half the women also received psychological debriefing at two weeks. Intrusion and avoidance scores were initially as high as those of post-trauma victims, but had significantly decreased by four months. Depression was not detected at any time point, but anxiety was significantly higher than community sample estimates at one week and four months. Psychological debriefing was perceived to be helpful, but did not influence emotional adaptation. A number of hypotheses are provided to explain these results. Outcome scores at one week significantly predicted outcome at four months, suggesting that early assessment would be important in determining which women should be offered intervention.", "To test whether critical incident stress debriefing after childbirth reduces the incidence of postnatal psychological disorders.\n Randomised single-blind controlled trial stratified for parity and delivery mode.\n Two large maternity hospitals in Perth.\n 1745 women who delivered healthy term infants between April 1996 and December 1997 (875 allocated to intervention and 870 to control group).\n An individual, standardised debriefing session based on the principles of critical incident stress debriefing carried out within 72 hours of delivery.\n Diagnosis of stress disorders or depression in the 12 months postpartum, using structured psychological interview and criteria of the Diagnostic and statistical manual of mental disorders, 4th edition.\n Follow-up information was available for 1730 women (99.1%), 482 of whom underwent psychological interview. There were no significant differences between control and intervention groups in scores on Impact of Events or Edinburgh Postnatal Depression Scales at 2, 6 or 12 months postpartum, or in proportions of women who met diagnostic criteria for a stress disorder (intervention, 0.6% v control, 0.8%; P = 0.58) or major or minor depression (intervention, 17.8% v control, 18.2%; relative risk [95% CI], 0.99 [0.87-1.11]) during the postpartum year. Nor were there differences in median time to onset of depression (intervention, 6 [interquartile range, 4-9] weeks v control, 4 [3-8] weeks; P = 0.84), or duration of depression (intervention, 24 [12-46] weeks v control, 22 [10-52] weeks; P = 0.98).\n There is a high prevalence of depression in women during the first year after childbirth. A session of midwife-led, critical incident stress debriefing was not effective in preventing postnatal psychological disorders, but had no adverse effects." ]

[ "1165499", "8284053", "11318460", "16684706", "18726988", "7466283", "4715098", "6939090", "21059594", "2392973", "17162478", "8352292", "1800294", "21091403", "10772609", "7395724", "7113926", "19800914", "8232998", "21193566", "12486782", "7987019", "9465571" ]

[ "The effectiveness of hearing protective devices.", "An epidemiologic method for assessing the effectiveness of hearing conservation programs using audiometric data.", "Active noise reduction in aviation helmets during a military jet trainer test flight.", "A study of hearing changes among military conscripts in the Swedish Army.", "The impact of hearing conservation programs on incidence of noise-induced hearing loss in Canadian workers.", "The difference in protection efficiency between earplugs and earmuffs. An investigation performed at a workplace.", "An evaluation of hearing conservation program--a five-year longitudinal study.", "The effect of long term use of hearing protectors in industrial noise.", "Use of historical data and a novel metric in the evaluation of the effectiveness of hearing conservation program components.", "Hearing conservation programs (HCPs): the effectiveness of one company's HCP in a 12-hr work shift environment.", "Noise exposure and hearing conservation in U.S. coal mines--a surveillance report.", "Five-year follow-up study of hearing loss at several locations within a large automobile company.", "A controlled investigation of in-field attenuation performance of selected insert, earmuff, and canal cap hearing protectors.", "A multi-component intervention to promote hearing protector use among construction workers.", "Use of comparison populations for evaluating the effectiveness of hearing loss prevention programs.", "An evaluation of the effectiveness of two different insert types of ear protection in preventing TTS in an industrial environment.", "Efficacy of enforcement in an industrial hearing conservation program.", "Hearing conservation program for agricultural students: short-term outcomes from a cluster-randomized trial with planned long-term follow-up.", "An evaluation of the U.S. Air Force's detailed follow-up audiometric examination program.", "Effect of daily noise exposure monitoring on annual rates of hearing loss in industrial workers.", "Changes over time in audiometric thresholds in a group of automobile stamping and assembly workers with a hearing conservation program.", "Early indicators of hearing conservation program performance.", "Noise attenuation of communication hearing protectors against impulses from assault rifle." ]

[ "The effectiveness of a hearing conservation program, and specifically the effectiveness of hearing protection devices (muffs in this case), was investigated over a five-year period, since the inception of the program at a major plant of the Ingersoll-Rand Company. The study concentrated on three groups (Class I, II, and III) of 213 employees whose noise level exposure did not change during the five-year study period. A hearing conservation criterion of 90dBA was utilized. One group consisted of office workers in which the level was well below this, a second group from a machine shop in which the level was slightly below the criterion, and a third group from foundry areas in which the levels were considerably above the 90dBA level. Personal ear protection was worn during the study period only by the last group. The mean differences in hearing levels were insignificant and were essentially the same in the three groups, at each frequency, and regardless of the baseline hearing thresholds. It is apparent that there were no significant changes in hearing threshodls during the study period among a non-noise exposed group; a mild to moderate noise-exposed group; and a group exposed to high levels of steady state noise, but wearing ear protectors. These results indicate that a hearing conservation program which includes audiometric testing and personal ear protection, utilizing a hearing conservation criterion of approximately 90dBA, does adequately protect the hearing of noise-exposed workers.", "A hearing conservation program (HCP) must include audiometric monitoring. In keeping with this requirement, enormous bodies of audiometric data have been accumulated. However, only a limited number of methods are available for using audiometric data to assess HCP effectiveness. This study illustrates an epidemiologic method. The risk of developing hearing loss (measured by the standard threshold shift) was compared between study and reference populations using the risk ratio. The study population had an increased risk of nearly 3-fold. Epidemiologic risk comparison methods, using reference populations, offer an alternative to current methods for HCP evaluation using audiometric data.", "Cockpit noise measurements were carried out in a two-seat jet trainer. For the continuous time and frequency analyses a two-channel tape-recording system was constructed of two miniature microphones connected through an amplifier to a digital tape-recorder. The analysed and averaged noise exposure including radio communication was 80-81 dB when the ANC system was on and 84-89 dB when the ANC system was off. For the conventional flight helmet the same noise exposure was 86 dB, and the noise exposure in the cockpit was 104-106 dB. The effect of the ANC system on the averaged noise exposure (L(Aeq8min)) was an improvement of 4-8 dB over the noise attenuation of the same helmets when the ANC system was off. Both ANC systems worked properly during the test flights. No severe ringing or voice circulation was found except during extreme vibration.", "The aim of the study was to investigate the incidence and the relative risk of significant threshold shift (STS, >or=15 dB deterioration at any ear and audiometric frequency) during primary military service (7-9 months), and to investigate whether subjects with an initial slight hearing loss (thresholds>or=25 dB HL at any audiometric frequency and ear) were under increased risk. The investigation was made as a prospective audiometric study and included 747 men. An age-matched group of 138 individuals served as an unexposed control group, whose incidence of STS was 2.9%. In the exposed group the incidence was 7.9% and the relative risk 2.7 risk ratio (RR). In the subgroup of 95 persons, who already at reporting-for-training had a mild hearing loss, the incidence was 17%. The relative risk for STS in this group compared to the control group was 6.8 (RR), and compared to those with normal hearing at reporting was 3.1 (RR). In spite of hearing conservation efforts, hearing deterioration still occurs, above all in the artillery. Those who already at reporting-for-training had a mild hearing loss were at higher risk for STS compared to those with initially normal hearing.", "Noise exposure remains one of the most ubiquitous of occupational hazards. Hearing conservation program legislation and the programs themselves were designed to lower risk of resulting occupational noise-induced hearing loss, but there has been no broad-based effort to assess the effectiveness of this policy.\n The incidence of a 10-dB standard threshold shift was examined in a group of Canadian lumber mill workers, using annual audiogram series obtained from the Workers' Compensation Board of British Columbia for the period 1979-1996 and using Cox proportional hazard models.\n Mean cumulative noise exposure was 98.1 dB-years. The audiograms from 22,376 individuals, among whom there were 2,839 threshold shifts of 10 dB or greater (i.e., a \"standard threshold shift\"), were retained in multivariable analyses. After adjusting for potential confounders, continuous use of hearing protection, and initial hearing tests later in the study period, the risk for standard threshold shift was reduced by 30%. Risk increased sixfold, however, in those with the highest noise exposure.\n Hearing conservation programs may be effective in reducing overall incidence of hearing loss. In the absence of noise control at source, however, highly exposed workers remain at unnecessary risk.\n Copyright 2008 Wiley-Liss, Inc.", "The hearing thresholds of shipyard workers have been measured with a Békésy sweep audiometer. The number of employees at different workplaces is so large that it is possible to select groups of workers of specified ages who have been employed by the shipyard for many years. These workers have used either earplugs of earmuffs for 5--10 years and have also been working all the time in almost the same noise environment. Three ways of investigation have been used to observe differences in the hearing levels between 'plug-men' and 'muff-men'. All three show a greater hearing impairment for 'muff-men' than for 'plug-men'. Under certain conditions earplugs provide the most effective protection although the attenuation is higher for earmuffs than for earplugs.", "nan", "nan", "To evaluate the effectiveness of hearing conservation programs (HCP) and their specific components in reducing noise-induced hearing loss (NIHL).\n This retrospective cohort study was conducted at one food-processing plant and two automotive plants. Audiometric and work-history databases were combined with historical noise monitoring data to develop a time-dependent exposure matrix for each plant. Historical changes in production and HCP implementation were collected from company records, employee interviews and focus groups. These data were used to develop time-dependent quality assessments for various HCP components. 5478 male (30,427 observations) and 1005 female (5816 observations) subjects were included in the analysis.\n Analyses were conducted separately for males and females. Females tended to have less NIHL at given exposure levels than males. Duration of noise exposure stratified by intensity (dBA) was a better predictor of NIHL than the standard equivalent continuous noise level (L(eq)) based upon a 3-dBA exchange. Within this cohort, efficient dBA strata for males were <95 versus ≥ 95, and for females <90 versus ≥ 90. The reported enforced use of hearing protection devices (HPDs) significantly reduced NIHL. The data did not have sufficient within-plant variation to determine the effectiveness of noise monitoring or worker training. An association between increased audiometric testing and NIHL was believed to be an artifact of increased participation in screening.\n Historical audiometric data combined with noise monitoring data can be used to better understand the effectiveness of HCPs. Regular collection and maintenance of quality data should be encouraged and used to monitor the effectiveness of these interventions.", "An existing hearing conservation program (HCP), originally designed when an 8-hr work shift schedule was in effect, was evaluated at a plant site where a 12-hr work shift schedule is now utilized. The study included the following phases: a noise analysis of the work environment, HCP evaluation through the use of audiometric data base analysis (ADBA), applying ADBA procedures and a comparison of the shift in hearing threshold levels (HTLs) for the 8-hr and 12-hr work shifts, and an evaluation of the hearing protection devices (HPDs) being used at the facility over the 12-hr work shift by measuring temporary threshold shift (TTS). The mean measured employee time-weighted average (TWA) in the process area where the TTS study was conducted was 92 dBA. It was found that the existing HCP is at best marginal. The most likely causes of this less-than-desirable rating are inadequate audiometric testing procedures and inadequate HPD utilization. Furthermore, it was concluded that, at this time, the introduction of the 12-hr work shift has had no impact on the level of effectiveness of the HCP. In evaluating the three HPDs in use at the facility (3-M foam earplug, E-A-R foam earplug, and Bilsom Soft earplug), it was found that they all offered effective protection from noise at all audiometric test frequencies (0.5 to 6 kHz) except 0.5 kHz. All three HPDs exhibited TTS at 0.5 kHz with the TTS measured significant at the p less than 0.05 level for the E-A-R and 3-M wearer groups.", "This study examines the patterns and trends in noise exposure documented in data collected by Mine Safety and Health Administration inspectors at U.S. coal mines from 1987 through 2004. During this period, MSHA issued a new regulation on occupational noise exposure that changed the regulatory requirements and enforcement policies. The data were examined to identify potential impacts from these changes. The overall annual median noise dose declined 67% for surface coal mining and 24% for underground coal mining, and the reduction in each group accelerated after promulgation of the new noise rule. However, not all mining occupations experienced a decrease. The exposure reduction was accompanied by an increase of shift length as represented by dosimeter sample duration. For coal miners exposed above the permissible exposure level, use of hearing protection devices increased from 61% to 89% during this period. Participation of miners exposed at or above the action level in hearing conservation programs rapidly reached 86% following the effective date of the noise rule. Based on inspection data, the occupational noise regulation appears to be having a strong positive impact on hearing conservation by reducing exposures and increasing the use of hearing protection devices and medical surveillance. However, the increase in shift duration and resulting reduction in recovery time may mitigate the gains somewhat.", "This longitudinal epidemiologic study was designed to investigate hearing loss over a 5-year period among noise-exposed employees of a large automobile company and to assess effectiveness of hearing conservation programs at locations representing the spectrum of operations (assembly, light manufacturing, heavy manufacturing and machining, metal fabrication, and founding). Based on computerized audiometric test data, the study summarizes methodology developed for measuring occupational hearing loss and its application in evaluating programs at these locations, which had maximal 8-hr time-weighted average (TWA) noise exposures ranging from 104 to 110 dB(A). Methods presented here provide for consideration of age and hearing level of study subjects at baseline audiogram and clearly demonstrate the extent of hearing loss during the study period. Among five study locations, the average hearing loss at 2,000-4,000 Hz in the worst-loss ear ranged from 3.4 to 6.2 dB over the follow-up period; after adjustment for presbycusis, the loss was less than 2 dB at all but one location, which showed a loss of nearly 4 dB. In comparison to a control group of nonnoise-exposed employees, hearing conservation programs at four of the five locations were judged to be effective. One location, a metal fabrication plant with a large percentage of employees having an 8-hr TWA noise exposure over 90 dB(A), was particularly noted for the effectiveness of its program.", "A field study assessed the actual spectral noise attenuation achieved by 40 industrial workers wearing four different hearing protection devices (HPDs) while on the job. The effect of two different HPD fitting procedures (subject fit vs. trained fit) on attenuation performance over two three-week periods of protector use was determined. Subjects were retrieved from their workplaces without prior knowledge of when they were to be tested and were not permitted to readjust the fit of their HPDs. Attenuation data were then collected using psychophysical procedures testing real ear attenuation at threshold. Statistical analyses indicated that the earplugs' attenuation significantly improved when training for proper fitting was used, whereas the earmuff and the ear canal cap were relatively insensitive to the training effect. The training was most effective for a slow-recovery foam plug over the three-week period. Results confirmed that laboratory protocols designed to simulate workplace influences on attenuation may not be relied on to yield reasonable estimates of field protection performance of HPDs, particularly for earplugs; however, the laboratory results were much better predictors of field protection for the earmuff. This study also demonstrated that the labeled manufacturers' noise reduction ratings (NRRs) substantially overestimated the actual field attenuation performance.", "Hearing protection devices (HPD) remain a primary method of prevention of noise-induced hearing loss despite their well-known limitations. A three-pronged intervention to increase HPD use was conducted among construction workers and included a baseline hearing loss prevention training, follow-up 'toolbox' (TB) reinforcement trainings, and use of a personal noise level indicator (NLI). A total of 176 subjects on eight sites completed three assessments. Prior to intervention, HPDs were used an average of 34.5% of the time and increased significantly, up about 12.1% after intervention and 7.5% two months after interventions were completed. The increase in HPD use was greatest among the group receiving both TB and NLI interventions; up about 25% from baseline, and this group was about two times more likely to use HPDs than the BL (baseline) training only group. This study demonstrates the mild impact of a well-constructed HPD use training and provides support for the additional use of a personal NLI to increase use of HPDs among construction workers. The most effective procedures for using such instruments require further exploration.", "One approach for evaluating the effectiveness of Hearing loss prevention programs (HLPPs) is to compare the rate of hearing loss in a study population with that in a reference population. This approach was used to evaluate the HLPP of a population of 14,900 employees of an industrial company with branches across the United States. Three reference populations were selected from a database of 22 industrial companies compiled under the sponsorship of the National Institute for Occupational Safety and Health. The risk of hearing loss in the study population was estimated relative to each of the three reference populations using the Cox proportional hazards model after adjustment for race, age at baseline, and hearing threshold at time of enrollment in the HLPP. In comparison with the three reference populations, hearing loss was 2.1 to 3.9 times more likely to occur in study population males and 1.8 to 5.1 times more likely in study population females. The 95% confidence interval around each risk estimate precluded unity, indicating that each risk estimate was statistically significant. These results indicate that the performance of the subject HLPP needs improvement. This study demonstrated the use of comparison populations for evaluating the effectiveness of HLPPs.", "The effectiveness of a V-51R insert hearing protector in preventing daily temporary threshold shifts in one industrial environment where the employees were exposed to an A-weighted energy average noise level of 95.6 dB was investigated. For comparison purposes the E-A-R Plug Insert hearing protector was also evaluated. The results indicated that the employees who wore the V-51R design incurred significant daily shifts in their hearing levels as compared to their initial hearing exam and significantly greater shifts than the employees who wore the E-A-R Plugs. The greater than expected measured shifts in hearing levels over the past six years in the two departments investigated is attributed at least partially to the use of the V-51R design.", "Relative efficacy of various levels of enforcement in the use of personal hearing protective devices was investigated among employees of a large industrial plant. The main variable was that each of four groups of employees worked during a different period of enforcement policy on the use of personal hearing protection. Analysis of variance of mean hearing levels using three different audiometric grading schemes with different levels of sensitivity, namely, the 0.5, 1, 2 kHz Hearing Level Index, the 1, 2, 3 kHz Hearing Level Index, and the 4000 Hz single puretone test indicate that the enforcement policy did have a dramatic effect on the efficacy of the hearing conservation program and should give similar results in other industrial settings. When and where the use of personal hearing protection was left to the employee it was found that hearing loss among the noise-exposed was very much in excess of that among a non-noise-exposed group. Mandatory use of personal protective devices was found to be much more effective in conserving hearing that the voluntary approach. Mandatory use of earmuffs exclusively proved to be less effective than mandatory use of personal hearing protection when the employee was given a choice of earmuffs or earplugs. Enactment of the Occupational Safety and Health Act did not result in greater hearing conservation over the existing company mandatory hearing conservation program which is quite effective.", "(1) To conduct a contemporary analysis of historical data on short-term efficacy of a 3-year hearing conservation program conducted from 1992 to 1996 in Wisconsin, USA, with 753 high school students actively involved in farm work; (2) to establish procedures for assessment of hearing loss for use in a recently funded follow-up of this same hearing conservation program cohort.\n We analyzed a pragmatic cluster-randomized controlled trial, with schools as the unit of randomization. Thirty-four rural schools were recruited and randomized to intervention or control. The intervention included classroom instruction, distribution of hearing protection devices, direct mailings, noise level assessments, and yearly audiometric testing. The control group received the audiometric testing.\n Students exposed to the hearing conservation program reported more frequent use of hearing protection devices, but there was no evidence of reduced levels of noise-induced hearing loss (NIHL).\n Our analysis suggests that, since NIHL is cumulative, a 3-year study was likely not long enough to evaluate the efficacy of this intervention. While improvements in reported use of hearing protection devices were noted, the lasting impact of these behaviors is unknown and the finding merits corroboration by longer term objective hearing tests. A follow-up study of the cohort has recently been started.", "The authors used information on individuals demonstrating permanent threshold shifts contained in the United States Air Force Hearing Conservation Data Registry to evaluate the effectiveness of detailed follow-up audiometric examinations as part of the USAF Hearing Conservation Program. Analysis yielded a relative risk of 1.00 with a 95% confidence interval of 0.97-1.03, which indicates a high probability that the true effect of these audiograms on the results of the next annual exam is minuscule, if not zero.", "Occupational noise-induced hearing loss (NIHL) is prevalent, yet evidence on the effectiveness of preventive interventions is lacking. The effectiveness of a new technology allowing workers to monitor daily at-ear noise exposure was analysed.\n Workers in the hearing conservation program of an aluminium smelter were recruited because of accelerated rates of hearing loss. The intervention consisted of daily monitoring of at-ear noise exposure and regular feedback on exposures from supervisors. The annual rate of change in high frequency hearing average at 2, 3 and 4 KHz before intervention (2000-2004) and 4 years after intervention (2006-2009) was determined. Annual rates of loss were compared between 78 intervention subjects and 234 controls in other company smelters matched for age, gender and high frequency hearing threshold level in 2005.\n Individuals monitoring daily noise exposure experienced on average no further worsening of high frequency hearing (average rate of hearing change at 2, 3 and 4 KHz = -0.5 dB/year). Matched controls also showed decelerating hearing loss, the difference in rates between the two groups being significant (p < 0.0001). Analysis of a subset of intervention subjects matched to controls for initial rate of hearing loss showed a similar trend but the difference was not statistically significant (p = 0.06).\n Monitoring daily occupational noise exposure inside hearing protection with ongoing administrative feedback apparently reduces the risk of occupational NIHL in industrial workers. Longer follow-up of these workers will help determine the significance of the intervention effect. Intervention studies for the prevention of NIHL need to include appropriate control groups.", "Noise induced hearing loss (NIHL) is among the 10 leading occupational diseases, afflicting between 7.4 and 10.2 million people who work in noise above 85 dBA. Although mandatory hearing conservation programs (HCPs) have been in effect since 1972, this problem persists, as hearing protectors are not consistently used by workers, or may not attenuate to manufacturer's estimates in real world conditions. In this study, information from noise and hearing protection use measurements taken at an automobile assembly plant were used to construct average lifetime noise exposure and hearing protection compliance estimates for use in modeling to predict both total hearing loss and onset of two accepted definitions of hearing loss. There were 301 males and females in this cohort; their mean age was 42.6 (7.2) years, and mean tenure was 14.3 (3.5) years. Average length of follow-up was 14.0 years. There were 16 members of this cohort who had hearing loss at the speech frequencies (defined as an average hearing level > or = 25 dB at 500, 1000, and 2000 Hz). In cross-sectional multivariate analyses, years of employment, male gender, and proportion of time wearing hearing protection were the factors most associated with hearing loss at the average of 2000, 3000, and 4000 Hz (p < 0.0001) controlling for age, transfer status (as a surrogate for previous noise exposure), race, and lifetime average noise exposure. The most consistent predictor of hearing loss in both univariate and multivariate analyses was percentage of time having used hearing protection during the workers' tenure.", "Retrospective analysis of initial audiograms from 21 hearing conservation programs (HCPs) revealed several statistical protocols capable of identifying HCPs of known performance. American National Standards Institute (ANSI) and Occupational Safety and Health Administration (OSHA) protocols clearly identified 3 HCPs known to have demonstrated excellent overall programs. ANSI and OSHA outcomes appeared equivalent in ability to provide early warnings of potentially unacceptable HCP practices.", "The noise attenuation values of commercial and military versions of earmuffs were measured using a Finnish assault rifle (RK762) as the sound source. The C-weighted peak level at the entrance of the left ear of the shooter was 156 dB (SD 1.0 dB; n = 25 shots). The noise was analyzed both outside and inside ear muffs on military volunteers on an open shooting range. All the earmuffs attenuated the C-weighted peak level to a value of less than 135 dB, which is less than the proposed values recommended by hearing damage criteria. Communication hearing protectors seem to function and attenuate sufficiently against the peak levels of the impulse noises used in this study." ]

[ "16352812", "12817519", "12747879", "16818273" ]

[ "A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia.", "Safety, tolerability, and pharmacokinetics of ICL670, a new orally active iron-chelating agent in patients with transfusion-dependent iron overload due to beta-thalassemia.", "Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, dose-escalation trial.", "Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload." ]

[ "Deferasirox (ICL670) is a once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. A comparative phase 3 trial was conducted to demonstrate the efficacy of deferasirox in regularly transfused patients with beta-thalassemia aged 2 years or older. Patients were randomized and received treatment with deferasirox (n = 296) or deferoxamine (n = 290), with dosing of each according to baseline liver iron concentration (LIC). The primary endpoint was maintenance or reduction of LIC; secondary endpoints included safety and tolerability, change in serum ferritin level, and net body iron balance. In both arms, patients with LIC values of 7 mg Fe/g dry weight (dw) or higher had significant and similar dose-dependent reductions in LIC and serum ferritin, and effects on net body iron balance. However, the primary endpoint was not met in the overall population, possibly due to the fact that proportionally lower doses of deferasirox relative to deferoxamine were administered to patients with LIC values less than 7 mg Fe/g dw. The most common adverse events included rash, gastrointestinal disturbances, and mild nonprogressive increases in serum creatinine. No agranulocytosis, arthropathy, or growth failure was associated with deferasirox administration. Deferasirox is a promising once-daily oral therapy for the treatment of transfusional iron overload.", "ICL670 is an orally active representative of a new class of tridentate iron chelator developed for the treatment of blood transfusion-dependent iron overload in chronic anemias. In this randomized, double-blind study, patients with transfusion-dependent beta-thalassemia received single oral doses of ICL670 ranging from 2.5 to 80 mg/kg to investigate its safety, tolerability, and pharmacokinetics and to obtain preliminary information on pharmacodynamic effects. ICL670 was well tolerated, and no safety problems occurred up to 80 mg/kg. A plasma half-life of 11 to 19 hours was found for ICL670, supporting once-daily oral administration. AUC0-24 h and Cmax of ICL670 increased nearly proportionally with the dose. The urinary excretion of ICL670 and its iron complex was less than 0.1% of the dose, and this was in accordance with the expected predominant iron fecal excretion induced by ICL670 (based on preclinical experiments). Notwithstanding, a positive trend toward increased amounts of urinary excreted iron was observed when the AUC0-24 h of ICL670 and the iron complex exceeded specific threshold values at the 40- and 80-mg/kg dose levels.", "Transfusional iron overload is a potentially fatal complication of the treatment of thalassaemia. We aimed to investigate short-term efficacy, pharmacokinetic/pharma- codynamic (PK/PD) relations, and safety of ICL670, a novel, tridentate, orally active iron chelator.\n We enrolled 24 patients and divided them into three cohorts consisting of a minimum of seven individuals. Patients were admitted to a metabolic unit and consumed a diet with a defined content of iron. Two patients in each cohort were randomly allocated placebo. Five or more patients received one daily dose of ICL670 at 10, 20, or 40 mg x kg(-1) x day(-1), from day 1 to 12. Net iron excretion (NIE) was measured between days 1 and 12. Primary objectives included assessment of safety and tolerability (measured by adverse events and clinical laboratory monitoring), pharmacokinetics (measured as drug and drug-iron complex), and cumulative net iron excretion (measured by faecal and urine output minus food input). Analysis was for efficacy.\n ICL670 was absorbed promptly and was detectable in the blood for 24 h. Exposure (area under the curve of plasma concentration) to ICL670 at pharmacokinetic steady state was proportional to dose. All three doses resulted in positive NIE. The NIE achieved at 20mg x kg(-1) day(-1) would prevent net iron accumulation in most patients transfused with 12-15 mL packed red-blood-cells kg(-1) month(-1), equivalent to 0.3-0.5 mg iron kg(-1) x day(-1). A linear relation (PK/PD) was recorded between exposure to ICL670 and total iron excretion, by contrast with placebo (r2=0.54, p<0.0001). Skin rashes were noted in four patients treated at 20 and 40 mg x kg(-1) x day(-1), and one patient also developed grade 2 transaminitis.\n ICL670 given once daily at 20 mg/kg seems to be an effective orally active iron chelator and is reasonably well tolerated. Long-term studies are now necessary to establish the practical contribution of this drug.", "Iron accumulation is an inevitable consequence of chronic blood transfusions and results in serious complications in the absence of chelation treatment to remove excess iron. Deferoxamine (Desferal, DFO) reduces morbidity and mortality although the administration schedule of slow, parenteral infusions several days each week limits compliance and negatively affects long-term outcome. Deferasirox (Exjade, ICL670) is an oral chelator with high iron-binding potency and selectivity. In a phase II study, the tolerability and efficacy of deferasirox were compared with those of DFO in 71 adults with transfusional hemosiderosis.\n Patients were randomized to receive once-daily deferasirox (10 or 20 mg/kg; n=24 in both groups) or DFO (40 mg/kg, 5 days/week; n=23) for 48 weeks. Results. Both treatments were well tolerated and no patient discontinued deferasirox due to drug-related adverse events. The reported frequency of transient, mild to moderate gastrointestinal disturbances was higher in the deferasirox group than in the DFO group, but these disturbances settled spontaneously without dose interruption in all patients. Decreases in liver iron concentration (LIC) were comparable in the deferasirox 20 mg/kg/day and DFO groups; baseline values of 8.5 and 7.9 mg Fe/g dw fell to 6.6 and 5.9 mg Fe/g dw, respectively, by week 48. Deferasirox showed a plasma elimination half-life of 8-16 hours, supporting its once-daily administration.\n Deferasirox at daily doses of 10 or 20 mg/kg was well tolerated and, at 20 mg/kg, showed similar efficacy to DFO 40 mg/kg in terms of decreases in LIC." ]

[ "12631309", "15527158", "16546538", "15117299", "11247549", "11165450", "11382368", "10864186", "9802271", "12971668", "10696421" ]

[ "Evaluation of efficacy of community-based vs. institutional-based direct observed short-course treatment for the control of tuberculosis in Kilombero district, Tanzania.", "Effectiveness of community-based directly observed treatment for tuberculosis in an urban setting in Tanzania: a randomised controlled trial.", "Family-member DOTS and community DOTS for tuberculosis control in Nepal: cluster-randomised controlled trial.", "Direct observation of treatment for tuberculosis: a randomized controlled trial of community health workers versus family members.", "Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan.", "Incentives vs outreach workers for latent tuberculosis treatment in drug users.", "A randomized, controlled trial of interventions to improve adherence to isoniazid therapy to prevent tuberculosis in injection drug users.", "A randomised controlled trial of lay health workers as direct observers for treatment of tuberculosis.", "Randomised controlled trial of self-supervised and directly observed treatment of tuberculosis.", "A randomised controlled clinical trial of the efficacy of family-based direct observation of anti-tuberculosis treatment in an urban, developed-country setting.", "Randomized controlled trial of directly observed treatment (DOT) for patients with pulmonary tuberculosis in Thailand." ]

[ "Tuberculosis (TB) has reappeared as a serious public health problem. Non-compliance to antituber-culous drug treatment is cited as one of the major obstacles to the containment of the epidemic. Compliance may be optimized by Directly Observed Treatment (DOT) and short-course treatment regimens. Since 1986, Tanzanian TB patients have received daily DOT at health facilities for the first 2 months of the treatment course. However, adherence and cure rates have been falling as the number of TB cases continues to increase and the burden on already stretched health facilities threatens to become unmanageable. We used an open cluster randomized controlled trial to compare community-based DOT (CBDOT) using a short-course drug regimen with institutional-based DOT (IBDOT). A total of 522 (301 IBDOT and 221 CBDOT) patients with sputum-positive TB were recruited. Overall, there was no significant difference in conversion and cure rates between the two strategies [M-H pooled odds ratio (OR) 0.62; 95% confidence interval (CI) 0.23, 1.71 and OR = 1.58; 95% CI 0.32, 7.88, respectively] suggesting that CBDOT may be a viable alternative to IBDOT. CBDOT may be particularly useful in parts of the country where people live far from health facilities.", "An urban district in Dar es Salaam city with a high tuberculosis (TB) caseload.\n To evaluate the effectiveness of community-based direct observation of treatment (DOT) using guardians and former TB patients compared to hospital-based DOT in an urban setting in Tanzania.\n Unblinded randomised control trial conducted in five sites under operational conditions in Temeke district. No changes to existing treatment delivery were made other than randomisation. The main outcome measure was treatment success. Analysis was by intention to treat.\n A total of 587 new tuberculosis patients were enrolled. Among enrolled patients, 260 were assigned to community-based DOT using guardians and former TB patients and 327 to health facility-based DOT. Both DOT options gave similar treatment outcomes. Treatment success rate among patients under community and health facility-based DOT were 85% and 83%, respectively (OR 1.17, 95%CI 0.75-1.83).\n Community-based DOT is as effective as health facility-based DOT and can achieve good treatment outcomes, even in countries with well functioning National Tuberculosis Programmes.", "A key component of the DOTS strategy for tuberculosis control (short-course chemotherapy following WHO guidelines) is direct observation of treatment. WHO technical guidelines recommend that health workers should undertake this part of the strategy, but will also accept direct observation of treatment in the community; WHO does not think that a family member should undertake this role. Supporting evidence for these recommendations is not available. The Nepal national tuberculosis programme asked us to develop and test a strategy of direct observation of treatment for the hill districts of Nepal, where direct observation of treatment by health workers is not feasible. We aimed to assess the success rates of two DOTS strategies developed for such areas.\n Between mid-July, 2002, and mid-July, 2003, we undertook a cluster-randomised controlled trial to compare two strategies-community DOTS and family-member DOTS--in ten hill and mountain districts of Nepal. Districts were used as the unit of randomisation. Primary outcome was success rate (proportion of registered patients who achieved cure or completed treatment), and analysis was by intention to treat.\n Five districts (549 patients) were allocated to community DOTS and five (358 patients) were allocated family-member DOTS. Community DOTS and family-member DOTS achieved success rates of 85% and 89%, respectively (odds ratio of success for community DOTS relative to family-member DOTS, 0.67 [95% CI 0.41-1.10]; p=0.09). Estimated case-finding rates were 63% with the community strategy and 44% with family-member DOTS.\n The family-member DOTS and community DOTS strategies can both attain international targets for treatment success under programme conditions, and thus are appropriate for the hill and mountain districts of Nepal. Both strategies might also be appropriate in other parts of the world where directly observed treatment by health workers is not feasible. Our findings lend support to adoption of this patient-responsive approach to direct observation of treatment within global tuberculosis control policy.", "We implemented community-based direct observation of treatment, short course (DOTS), including a randomized controlled trial of direct observation either by community health workers (CHWs) or family members, under operational conditions in a region of Swaziland. There was a high death rate of 15%, due to the high HIV rates in the region. There was no significant difference in the cure and completion rate between direct observation of treatment by CHWs and family members [2% difference (95% CI -3% to 7%), exact P = 0.52]. A before-and-after comparison of outcomes demonstrated that the cure and treatment completion rate improved from a baseline of 27-67% following implementation of community-based DOTS. We conclude that community-based tuberculosis DOTS can improve successful outcomes of treatment. However, direct observation can be undertaken effectively using either daily family or CHW supervision. The choice of treatment supporter should be based on access, patient preference and availability of CHW resource.", "DOTS is the control strategy for tuberculosis promoted by WHO. Pakistan is currently developing its National Tuberculosis Programme, and requires guidance on types of direct observation of treatment appropriate for the local conditions. We did a randomised trial to assess the effectiveness of different packages for tuberculosis treatment under operational conditions in Pakistan.\n We enrolled 497 adults with new sputum-positive tuberculosis. 170 were assigned DOTS with direct observation of treatment by health workers; 165 were assigned DOTS with direct observation of treatment by family members; and 162 were assigned self-administered treatment. The trial was done at three sites that provide tuberculosis services strengthened according to WHO guidelines for the purposes of the research, with a standard daily short-course drugs regimen (2 months of isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by 6 months of isoniazid and ethambutol). The main outcome measures were cure, and cure or treatment completion. Analysis was by intention to treat.\n Within the strengthened tuberculosis services, the health-worker DOTS, family-member DOTS, and self-administered treatment strategies gave very similar outcomes, with cure rates of 64%, 55%, and 62%, respectively, and cure or treatment-completed rates of 67%, 62%, and 65%, respectively.\n None of the three strategies tested was shown to be superior to the others, and direct observation of treatment did not give any additional improvement in cure rates. The effectiveness of direct observation of treatment remains unclear, and further operational research is needed.", "Drug users are at increased risk for latent tuberculosis infection (LTBI) and also at increased risk for noncompletion of medication regimens for treatment of LTBI or tuberculosis disease. Directly observed therapy (DOT) provided by outreach workers, the use of incentives, or both have been suggested as a means to increase adherence.\n To compare the independent and combined effects of monetary incentives and outreach worker provision of DOT for LTBI treatment in a sample of active drug users.\n The research design was a randomized controlled trial in a community outreach program setting. Participants consisted of a volunteer sample of 163 active injection drug and crack cocaine users placed on twice weekly DOT. Condition 1 of the interventions consisted of provision of DOT by an outreach worker at a location chosen by the participant (active outreach) and a $5 per visit incentive. Condition 2 was comprised of active outreach with no monetary incentive, and Condition 3, provision of DOT at the study community site and a $5 per visit incentive. The main outcome measures were percentage of medication taken as prescribed and completion of medication regimen.\n The percentage of prescribed medication taken was higher for those who received incentives, either with (71%) or without (68%) active outreach, compared to those who received active outreach alone (13%). Only 4% of participants assigned to Condition 2 completed treatment, compared to 53% of Condition 1 participants, and 60% of Condition 3 participants.\n Monetary incentives were clearly superior to active outreach. Active outreach in combination with monetary incentives did not increase adherence over incentives alone.", "To determine the effect of several interventions on adherence to tuberculosis preventive therapy.\n We conducted a randomized trial with a factorial design comparing strategies for improving adherence to isoniazid preventive therapy in 300 injection drug users with reactive tuberculin tests and no evidence of active tuberculosis. Patients were assigned to receive directly observed isoniazid preventive therapy twice weekly (Supervised group, n = 99), daily self-administered isoniazid with peer counseling and education (Peer group, n = 101), or routine care (Routine group, n = 100). Patients within each arm were also randomly assigned to receive an immediate or deferred monthly $10 stipend for maintaining adherence. The endpoints of the trial were completing 6 months of treatment, pill-taking as measured by self-report or observation, isoniazid metabolites present in urine, and bottle opening as determined by electronic monitors in a subset of patients.\n Completion of therapy was 80% for patients in the Supervised group, 78% in the Peer group, and 79% in the Routine group (P = 0.70). Completion was 83% (125 of 150) among patients receiving immediate incentives versus 75% (112 of 150) among patients with deferred incentives (P = 0.09). The proportion of patients who were observed or reported taking at least 80% of their doses was 82% for the Supervised arm of the study, compared with 71% for the Peer arm and 90% for the Routine arm. The proportion of patients who took 100% of doses was 77% for the Supervised arm (by observation), 6% for the Peer arm (by report), and 10% for the Routine arm (by report; P <0.001). Direct observation showed the median proportion of doses taken by the Supervised group was 100%, while electronic monitoring in a subset of patients showed the Peer group (n = 27) took 57% of prescribed doses and the Routine group (n = 32) took 49% (P <0.001). Patients in the Routine arm overreported adherence by twofold when data from electronic monitoring were used as a gold standard. There were no significant differences in electronically monitored adherence by type of incentive.\n Adherence to isoniazid preventive therapy by injection drug users is best with supervised care. Peer counseling improves adherence over routine care, as measured by electronic monitoring of pill caps, and patients receiving peer counseling more accurately reported their adherence. More widespread use of supervised care could contribute to reductions in tuberculosis rates among drug users and possibly other high-risk groups.", "Study conducted in a suburb of Cape Town, South Africa.\n Comparison of successful tuberculosis treatment outcome rates between self supervision, supervision by lay health worker (LHW), and supervision by clinic nurse.\n Open, randomised, controlled trial with intention-to-treat analysis.\n All groups (n = 156) achieved similar outcomes (LHW vs. clinic nurse: risk difference 17.2%, 95% confidence interval [CI] -0.1-34.5; LHW vs. self supervision 15%, 95%CI -3.7-33.6). New patients benefit from LHW supervision (LHW vs clinic nurse: risk difference 24.2%, 95%CI 6-42.5, LHW vs. self supervision 39.1%, 95%CI 17.8-60.3) as do female patients (LHW vs. clinic nurse 48.3%, 95%CI 22.8-73.8, LHW vs. self supervision 32.6%, 95%CI 6.4-58.7).\n LHW supervision approaches statistically significant superiority, but fails to reach it most likely due to the study's limitation, the small sample size. It is possible that subgroups (new and female patients) do well under LHW supervision. LHW supervision could be offered as one of several supervision options within TB control programmes.", "Tuberculosis is a major public-health problem in South Africa, made worse by poor adherence to and frequent interruption of treatment. Direct observation (DO) of tuberculosis patients taking their drugs is supposed to improve treatment completion and outcome. We compared DO with self-supervision, in which patients on the same drug regimen are not observed taking their pills, to assess the effect of each on the success of tuberculosis treatment.\n We undertook an unblinded randomised controlled trial in two communities with large tuberculosis caseloads. The trial included 216 adults who started pulmonary tuberculosis treatment for the first time, or who had a second course of treatment (retreatment patients). No changes to existing treatment delivery were made other than randomisation. Analysis was by intention to treat. Individual patient data from the two communities were combined.\n Treatment for tuberculosis was more successful among self-supervised patients (60% of patients) than among those on DO (54% of patients, difference between groups 6% [90% CI -5.1 to 17.0]). Retreatment patients had significantly more successful treatment outcomes if self-supervised (74% of patients) than on DO (42% of patients, difference between groups 32% [11%-52%]).\n At high rates of treatment interruption, self-supervision achieved equivalent outcomes to clinic DO at lower cost. Self-supervision achieved better outcomes for retreatment patients. Supportive patient-carer relations, rather than the authoritarian surveillance implicit in DO, may improve treatment outcomes and help to control tuberculosis.", "A randomised, controlled clinical trial of the effectiveness of a family-based programme of directly observed treatment (DOT) for tuberculosis.\n TB patients seen in Victoria, Australia, were randomly allocated to DOT observed by a family member (FDOT), or to standard supervised but non-observed therapy (ST). The outcome measure was compliance, measured by blinded testing of isoniazid levels in urine. An intention-to-treat analysis was used.\n Of 173 patients, 87 were allocated to FDOT and 86 to ST. Only 58% in the FDOT group were able to receive FDOT, the major reason being living alone and not having a family member to observe treatment. The rate of non-compliance was 24% (41/173), with no significant difference between FDOT (22/87) and ST (19/86). No clinical or socio-demographic variable predicted compliance.\n We were unable to demonstrate a benefit of FDOT in an urban, industrialised country setting. FDOT may be more appropriate in developing countries, where extended family support is often available and the burden of TB is much higher. Poor compliance and the difficulty in predicting non-compliance shown in this study highlights the need for DOT for all TB patients.", "While directly observed treatment (DOT) has been recommended as the standard approach to tuberculosis control, empirical data on its feasibility and efficiency are still scarce. We conducted a controlled trial of DOT at 15 health care facilities at various levels of the government health care system in Thailand. A total of 836 patients diagnosed between August 1996 and October 1997 were randomly assigned to be treated either under DOT or self-supervised using monthly drug supplies (SS). Options for treatment supervisors were health staff, community members or members of the patients' families. Treatment outcomes were compared on the basis of cure, treatment-completion, default and death rates. In both study arms, treatment outcomes were improved compared to pre-study conditions. Cure and treatment-completion rates were significantly higher in the DOT cohort (76% and 84%) than in the SS group (67% and 76%). The benefits of DOT were more pronounced at district and provincial hospitals (DOT cure rate 81% vs. 69% in the SS group), while differences for patients treated at referral centres were non-significant (DOT cure rate 72% vs. 66% in the SS group). No significant differences in outcomes could be observed between patient groups receiving DOT under the various options for treatment supervisors. DOT appears especially suited for treatment at decentralized facilities. While a general focus on programme performance can improve outcomes, DOT provides significant additional benefits. If basic conditions are met, a DOT strategy can be tailored to country-specific conditions by exploring multiple observation options, without decreasing its effectiveness." ]

[ "16033337", "2321772", "9420391", "2914336", "3565725", "2361329", "2197001", "8818089", "2403851", "1567037", "1784364", "2205129", "2271192", "1288904", "8279255", "2185814", "1997058", "2774259", "11226995" ]

[ "Randomized trial comparing overnight preoperative fasting period Vs oral administration of apple juice at 06:00-06:30 am in pediatric orthopedic surgical patients.", "Ingestion of liquids compared with preoperative fasting in pediatric outpatients.", "The effect of pre-operative intake of oral water and ranitidine on gastric fluid volume and pH in children undergoing elective surgery.", "The effect of preoperative apple juice on gastric contents, thirst, and hunger in children.", "The effect of different pre-operative feeding regimens on plasma glucose and gastric volume and pH in infancy.", "Unlimited clear fluid ingestion by infants up to 2 hours before surgery is safe.", "Clear fluids three hours before surgery do not affect the gastric fluid contents of children.", "[Possibility of rice porridge for preoperative feeding in children].", "Large volumes of apple juice preoperatively do not affect gastric pH and volume in children.", "Shortened preanesthetic fasting interval in pediatric cardiac surgical patients.", "[Preoperative fasting in pediatrics].", "Effects of duration of fasting on gastric fluid pH and volume in healthy children.", "Gastric residual volume in infants and children following a 3-hour fast.", "Efficacy, duration, and absorption of a paediatric oral liquid preparation of ranitidine hydrochloride.", "Effects of 2-, 4- and 12-hour fasting intervals on preoperative gastric fluid pH and volume, and plasma glucose and lipid homeostasis in children.", "Paediatric glucose homeostasis during anaesthesia.", "Ingestion of clear fluids is safe for adolescents up to 3 h before anaesthesia.", "Effect of oral liquids and ranitidine on gastric fluid volume and pH in children undergoing outpatient surgery.", "Benefits of oral administration of an electrolyte solution interrupting a prolonged preoperatory fasting period in pediatric patients." ]

[ "We aimed to evaluate the efficacy of clear liquids orally administered at 06:00-06:30 am on the morning of surgery to reduce prolonged preoperative fasting periods.\n After obtaining informed parental consent, 100 children undergoing scheduled orthopedic surgical procedures, ASA I-II, were randomly allocated to two groups. In group 1, children underwent the typical overnight preoperative period and patients in group 2 received a commercial brand of apple juice (glucose 28 g in 250 ml) at 06:00-06:30 am on the day of surgery. Patients <3 years old received 15 ml.kg(-1) and older children 10 ml.kg(-1) to a maximum volume of 250 ml. All patients underwent overnight fasting for milk and solids.\n Fasting time was 4.8 +/- 2.1 h (ranging from 3 to 11 h) in the group receiving apple juice at 06:00-06:30 am and 13.2 +/- 3.3 h (ranging from 5 to 19 h) in the overnight-fasting group (P < 0.05; 95% CI: -9.6 to -7.4 h). More patients were irritable (odds ratio, OR 4.5; 95% CI: 1.9-10.8) and dehydrated (OR 21.6; 95% CI: 5.9-79.0) in the overnight-fasting group. Glucose levels <2.7 mmol.l(-1) (50 mg.dl(-1)) were not reported in any case.\n A 15 ml.kg(-1) of apple juice for patients of <3 years of age or 10 ml.kg(-1) for older children, at 06:00-06:30 am of the surgical morning is a simple procedure to prevent dehydration and to produce positive behavior in low-risk, pediatric surgical patients.", "The preoperative fast is often an unpleasant preoperative experience that might be alleviated by allowing children to drink clear liquids. The authors compared gastric fluid volume and pH in two groups of children, one of whom was permitted clear liquids until 2 h before surgery (study group) and the other followed routine preoperative fasting orders (control group). The study group was not limited in the quantity of clear liquid allowed with the exception that the last intake prior to surgery was limited to 8 ounces. The study group (n = 53) averaged 5.9 +/- 5 yr and weighed 23.6 +/- 17 kg, while the control group averaged 7.3 +/- 4.6 yr and weighed 29 +/- 17.7 kg (P = NS). Gastric contents were aspirated following induction of anesthesia. Gastric fluid volume averaged 0.44 +/- 0.51 ml/kg for study group and 0.57 +/- 0.51 ml/kg in the control group (P = 0.12). Of the study patients, 48% had a measured gastric fluid volume greater than or equal to 0.4 ml/kg compared with 58% of the control patients (P = 0.77). Eighty three patients had sufficient gastric fluid for pH determination; of these 34/35 (97%) in the study group and 44/48 (92%) in the control group had a gastric fluid pH less than or equal to 2.5. Using a linear analog scale parents rated the children in the study group to be less irritable (P less than 0.001) and to have had a better overall preoperative experience (P less than 0.01) compared with the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effect of pre-operative intake of oral water and ranitidine on gastric fluid volume and pH was studied in 75 children of American Society of Anesthetists (ASA) grade I and grade II undergoing elective surgery. Group I patients fasted from midnight and acted as control. Group II patients received 5 ml/kg plain water orally 3 hours before surgery. Group III children received 5 ml/kg of plain water and 2 mg/kg of ranitidine orally 3 hours before surgery. Mean volume of gastric aspirate was comparable in all 3 groups (p > 0.05). Mean pH was significantly higher in ranitidine treated patients (5.12 +/- 1.73) as compared to non-ranitidine treated patients (2.26 +/- 0.57 and 2.53 +/ 0.79 in group I and group II respectively). Number of patients at risk (pH < or = 2.5 and volume > or = 0.4 ml/kg) was not significantly different in group I and group II. Mean thirst and behaviour scores were significantly higher in fluid treated patients (groups II and III) as compared to control (p < 0.01). To conclude, administration of pre-operative water (5 ml/kg) along with ranitidine (2 mg/kg) favourably modifies gastric fluid volume and pH, improves patient behaviour and minimises the number of patients at risk of aspiration pneumonitis, should the child aspirate.", "The effect of 3 ml.kg-1 of apple juice given 2.6 +/- 0.4 hours preoperatively was investigated in 80 healthy children of ages five to ten years in this prospective, randomized, single blind study. The children who drank apple juice preoperatively had decreased gastric volume, thirst, and hunger (p less than 0.05). The gastric volume in the control group was 0.43 +/- 0.46 ml.kg-1 and in the patients who received apple juice the gastric volume was 0.24 +/- 0.31 ml.kg-1. The gastric pH was not significantly different, with the control group's gastric pH being 1.7 +/- 0.6 and the treated group's pH was 2.2 +/- 1.2. Further studies of the effects of different volumes and timing of preoperative clear fluids are indicated in paediatric patients.", "The effects of four different pre-operative feeding regimens were studied in 123 children below the age of one year presenting for surgery. Plasma glucose concentrations, blood acid-base values, gastric volume and gastric pH were measured before and after induction of anaesthesia. No patient was found to be hypoglycaemic and there were no significant differences in plasma glucose concentration and acid-base values between the groups. No correlation was demonstrated between the age and weight of the patients and the duration of fasting and the plasma glucose concentration. There was a significant elevation of plasma glucose concentration in all four groups after induction of anaesthesia (P less than 0.001) compared with the pre-induction level which is a reflection of the stress of blood sampling and induction of anaesthesia. Infants less than three months of age in the milk-feed group had a significantly higher gastric volume with low pH (P less than 0.05) signifying a potentially greater risk of pulmonary acid aspiration. The practice of timing the last pre-operative feed in infancy according to the infant's normal feeding pattern does not appear to increase the risk factors for pulmonary aspiration, if milk is avoided.", "nan", "This prospective, randomized, single-blind study of 121 healthy children aged 2 to 12 yr investigated the effect of clear fluids on gastric contents. Gastric fluid volume and pH were measured immediately following the induction of general anaesthesia and were not significantly affected by the ingestion of unlimited clear fluids up to three hours preoperatively. After a prolonged fast (mean fast 14 hr), gastric fluid volume was 0.39 +/- 0.37 ml.kg-1 and gastric pH was 1.7 +/- 0.4; after unlimited clear fluids (203 +/- 109 ml) up to three hours before surgery gastric fluid volume was 0.34 +/- 0.28 ml.kg-1 and gastric pH was 1.8 +/- 0.7 (mean +/- SD). Gastric fluid volume (ml.kg-1) increased in both the control and study groups as age increased, P less than 0.005. It is concluded that drinking clear fluid up to three hours before scheduled surgery does not have a measurable effect on gastric volume and pH of healthy children of ages 2 to 12 yr.", "To determine the effect of rice porridge feeding before elective surgery on preoperative gastric fluid pH, volume and starvation, a prospective study was undertaken in pediatric patients. Twenty healthy children ranged in age from 5 to 12 years were allocated randomly to either a fasted or rice porridge group. The children of fasted group (control group) were allowed to take solid food until midnight before the operation. The rice porridge group (study group) patients received a small amount of rice porridge 5 hours 30 minutes before the induction of anesthesia. The patients of both groups were permitted to take clear fluid until 5 hours before the induction of anesthesia. After the induction of anesthesia, gastric fluid was aspirated through an orogastric tube. The mean gastric fluid volume was 0.43 +/- 0.32 ml.kg-1 in the control group and 0.5 +/- 0.6 ml.kg-1 in the study group. The mean gastric fluid pH was 1.43 +/- 0.27 ml.kg-1 in the control group and 1.89 +/- 0.75 ml.kg-1 in the study group. There were no significant differences between the two groups concerning the gastric fluid volume and pH. The patient of the study group complained of less hunger. Preoperative rice porridge feeding is a possible preoperative feeding for pediatric patients.", "The effect on gastric pH and volume of 0, 6 and 10 ml.kg-1, of apple juice given 2.5 hours before surgery to children aged five to ten years was investigated in this prospective, randomized, single-blind study. Gastric contents were aspirated after induction of anaesthesia, and the volume measured. The pH of the gastric aspirate was then assessed using pH paper. Neither gastric volume nor pH immediately following the induction of general anaesthesia were significantly different among the three groups. Gastric volumes after 0, 6 and 10 ml.kg-1, of juice averaged (mean +/- SD) 0.45 +/- 0.31, 0.66 +/- 0.79 and 0.71 +/- 0.76 ml.kg-1, respectively; gastric pH averaged 1.7 +/- 0.6, 1.7 +/- 0.6 and 1.8 +/- 0.8, respectively. On the basis of questions asked immediately before induction of anaesthesia, patients who drank 6 ml.kg-1 of apple juice had decreased thirst and were less irritable and upset before anaesthesia than those who had not (P less than 0.05). It is concluded that drinking large volumes of clear apple juice 2.5 hours before scheduled surgery does not have a measurable effect on gastric volume and pH and may offer benefits such as improved patient comfort.", "The recent liberalization of preoperative feeding orders in healthy pediatric outpatients prompts the question of whether this applies to children about to have cardiac surgery. The authors compared gastric fluid volume and pH in two groups of children undergoing elective cardiac surgery, one of which was not only permitted ad libitum clear liquids but was mandated to drink clear liquids 2-3 h before induction of anesthesia (study group). The other group followed routine inpatient preoperative fasting orders (control group). The study group (n = 44) averaged 3.1 +/- 4.1 yr and weighed 15.3 +/- 16.3 kg; the control group averaged 3.3 +/- 3.9 yr and weighed 14.3 +/- 12.1 kg (P = 0.82, 0.73, respectively). Aspiration of residual gastric fluid volume was attempted in all patients after induction of anesthesia. Gastric fluid volume averaged 0.6 +/- 0.9 mL/kg in the study group and 0.4 +/- 0.6 mL/kg in the control group (P = 0.13). Of the study patients, 41% had a measured gastric volume greater than or equal to 0.4 mL/kg compared with 32% of the control patients (P = 0.50). Of the 42 patients who had residual gastric fluid aspirated, pH determinations were completed on 37 aspirates; of these 19 of 20 (95%) in the study group and 14 of 17 (82%) in the control group had a gastric pH less than or equal to 2.5. Using a linear analogue scale, parents rated children in the study group to be more comfortable, less hungry, and less thirsty compared with the control patients (P = 0.004, 0.002, 0.0001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "To determine the effects of duration of fasting before elective surgery on gastric fluid pH and volume in children, a prospective, randomized, blinded study of 100 unpremedicated children, aged 1-14 yr, was undertaken. Each child was given 2 mL/kg of water orally and then fasted 2, 4, or 6 h preoperatively. After induction of anesthesia and tracheal intubation, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube. Gastric fluid pH was measured using a calibrated PHM62 radiometer. Gastric fluid volume was the total volume of fluid aspirated from the stomach. The duration of fasting was between 2.0 and 8.5 h. We found that neither gastric fluid pH nor gastric fluid volume correlated with the duration of fasting. The mean (+/- SD) gastric fluid pH was 1.80 +/- 0.79 and the mean (+/- SD) gastric fluid volume was 0.56 +/- 0.39 mL/kg. Gastric fluid pH was less than 2.5 and volume greater than 0.4 mL/kg in 53% of children. We conclude that healthy children may receive 2 mL/kg of water up to 2 h before elective surgery without decreasing gastric fluid pH or increasing gastric fluid volume beyond values obtained after fasting for 6 h.", "The effect of a 3-hour versus a 10-hour preoperative fasting interval on the gastric residual volume and gastric pH of pediatric patients was evaluated. Forty-four healthy infants, 1 month to 5 years of age, were randomly assigned to one of two groups. The 3-hour nil per os (NPO) group consisted of 19 infants kept NPO for 3 hours following ingestion of up to 4 ounces of 5% dextrose in water (D5W). The control group consisted of 25 infants who remained NPO an average of 10 hours prior to surgery. Gastric residual volume was calculated using the dye-dilution technique. After the dye marker was injected into the stomach, complete aspiration of the stomach (including the volume of dye marker plus residual gastric contents) was attempted as another method to measure gastric residual volume. There were no significant differences in gastric residual volume between the 3-hour and the 10-hour NPO groups using either the dye-dilution or aspiration methods. However, there were significant differences between the two measuring techniques. Gastric residual volume was significantly greater in volume when measured by the dye-dilution technique than it was when measured by the aspiration technique in both the 10-hour (p less than 0.009) and the 3-hour (p less than 0.0009) NPO groups. Complete aspiration of a known volume of fluid injected through the orogastric tube was not possible in 23 of the 44 (52.4%) infants. Mean gastric pH was less than 2.0 in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "The objectives of this study were to assess the clinical efficacy of a new oral ranitidine liquid preparation in reducing gastric acidity and volume, to determine the degree of absorption of the drug, and to determine the duration of drug effect. Eighty preoperative children between the ages of one and six years were enrolled in each of three centres. Each subject was allocated to one of the following groups: Group A - apple juice, 5 ml.kg-1 plus placebo liquid; Group B - apple juice, 5 ml.kg-1 plus ranitidine hydrochloride 2 mg.kg-1; Group C - water, 5 ml and placebo liquid; or Group D - water, 5 ml and ranitidine liquid 2 mg.kg-1. All study agents were administered at least two hours before surgery along with a dye marker, sulfobromophthalein 1 ml (50 mg.ml-1). Following induction of anaesthesia, gastric fluid was aspirated, and analyzed for pH, volume, and sulfobromophthalein content (as an index of the ingested fluids). A serum sample was also drawn and analyzed for ranitidine content by high performance liquid chromatography. Groups B and D had fewer subjects with pH below 2.5 and gastric volume > 0.4 ml.kg-1. The duration of reduced volume and acidity was shown to be greatest from two to four hours after drug administration. Thirty-three percent of subjects receiving oral ranitidine, 2 mg.kg-1 hydrochloride as a single dose demonstrated no measurable effect on gastric pH and volume; 28 of those subjects had adequate ranitidine serum levels.", "We evaluated 105 randomly-selected unpremedicated children aged 1-14 years to determine the effects of a 2-, 4- and 12-h preoperative fasting interval on the preoperative gastric fluid pH and volume, and plasma glucose and lipid homeostasis. Each child undergoing elective surgery ingested a large volume (approximately 10 ml/kg b.w.) of apple juice and then fasted for 2, 4 or 12 h before the estimated induction of anaesthesia. After induction of anaesthesia, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube. Plasma concentrations of glucose, total ketone bodies, non-esterified fatty acid (NEFA), triglycerides, and cortisol were measured at the time of induction to evaluate the fasting interval effects on preoperative plasma glucose and lipid homeostasis. There were no significant differences between the three groups in either gastric fluid volume or pH. In addition, there were no significant differences between the groups with respect to the proportion with a pH < 2.5 and volume > 0.4 ml/kg b.w. Neither plasma concentrations of glucose, triglycerides, nor cortisol at the time of anaesthetic induction differed between the three groups. Both 4 and 12 h nil per os (NPO) caused an increase in lipolysis, which was presumably a compensatory mechanism to maintain normoglycaemia. The plasma NEFA and total ketone bodies concentrations were therefore significantly higher in these two fasting intervals than in 2 h NPO. These data suggest that a 2-h NPO, after a large volume of ingested apple juice, may offer additional benefits by preventing an increase in lipolysis during the fasting interval without either increasing the volume of gastric fluid or decreasing the gastric pH.(ABSTRACT TRUNCATED AT 250 WORDS)", "The perioperative blood glucose regulatory response was compared in 20 healthy children (aged 1-5 yr) presenting for minor surgery and allocated randomly to either a fasted or a glucose group. All children received a milk feed at midnight. The fasted group received no oral intake thereafter, whereas the glucose group received 5% dextrose water 10 ml kg-1 orally about 4 h before operation. The mean plasma glucose concentrations in the two groups were similar before operation and were within normal limits. The pattern of change in the concentrations of plasma glucose, insulin, cortisol, growth hormone and glucagon were also similar between the two groups. Ten percent of patients in the fasted group and 33% in the glucose group had gastric aspirates in excess of 0.4 ml kg-1. The pH of all gastric samples was less than 2.5. The results suggest that healthy preschool children were able to maintain glucose homeostasis after 8 h of fasting. Feeding within 4-6 h before surgery may increase the risk of pulmonary aspiration.", "We have studied the effect of ingestion of unlimited clear fluids by adolescents up to 3 h before anaesthesia to determine the effect this fluid ingestion would have on thirst, hunger and gastric contents at induction of anaesthesia. We studied prospectively 152 adolescents (ages 13-19 yr) undergoing elective surgery. Fifty percent of the patients had nothing by mouth after midnight. The other 50% were instructed to ingest unlimited clear fluids up to 3 h before surgery. On arrival in the operating room, subjects were asked to assess thirst and hunger with a linear analogue scale of 0-10 (0 corresponding to no thirst or no hunger). After induction of anaesthesia, gastric contents were aspirated via a 16-French gauge orogastric tube. Gastric fluid volume (GV) was measured with a syringe and gastric pH (GpH) was assessed with Merck pH strips. GV, GpH and subject hunger were unaffected by ingestion of clear fluids. Subject thirst was reduced by clear fluids. It is concluded that unlimited clear fluid ingestion by healthy adolescents up to 3 h before operation decreases thirst and does not affect gastric contents.", "Eighty-eight children (mean age 5.6 yr, range 1-14 yr) about to undergo elective outpatient surgery were randomly assigned to four groups. All children were given phenolsulfonphthalein (PSP) orally 2-3 h before the scheduled time of surgery as a marker dye to assess gastric emptying. Immediately after receiving PSP they were given: group A--liquids, up to 5 ml/kg + placebo (glucose water 0.2 ml/kg); group B--liquids, up to 5 ml/kg + ranitidine 2 mg/kg in glucose water 0.2 ml/kg; group C--placebo only; group D--ranitidine only. Gastric contents were aspirated after induction of anesthesia. Mean volume (range) in ml/kg of aspirated gastric fluid in each group was: group A--0.34 (0-1.0); group B--0.17 (0.07); group C--0.25 (0-1.1); group D--0.16 (0-0.6). The pH mean (range) value was: group A--1.83 (0.9-3.6); group B--4.76 (2.0-7.7); group C--2.10 (1.2-4.1); group D--3.97 (1.3-7.3). PSP could not be detected in the gastric samples from children in whom the ingestion-sampling interval was more than 2.25 h. In comparison with prolonged starvation, administration of oral liquids without ranitidine 2-3 h preoperatively did not produce a significant increase in mean volume of gastric aspirate, and there was no increase in the number of patients with gastric aspirate greater than 0.4 ml/kg. Administration of ranitidine with or without fluids resulted in a decrease in both volume and acidity of gastric contents.", "The aim of this study was to evaluate the benefits of an oral isosmolar solution of electrolytes (ISE) administered to interrupt a prolonged fasting period in children undergoing an elective surgical procedure under general anesthesia.\n Forty unpremedicated children aged 3 to 12 years, ASA I, undergoing a surgical procedure requiring general anesthesia were assigned randomly to 1 of 2 groups. Group 1 consisted of patients with an overnight fasting period for milk and solids of at least 8 hours. In group 2, patients under a similar fasting period received a volume of 4 mL/kg of an oral ISE 3 hours before completing the fasting period. After anesthetic induction, blood glucose level (BGL) was quantified, and patients underwent an endoscopic examination to obtain the gastric content to determine the residual gastric volume (RGV) and pH levels.\n In group 1, the RGV was 0.78 +/- 0.44 mL/kg, pH was 1.75 +/- 0.38, and BGL was 86.4 +/- 14.5. In group 2, the RGV was 0.40 +/- 0.29 mL/kg, pH was 3.18 +/- 0.61, and BGL was 85.1 +/- 12.6. Only RGV and pH were significantly different between groups.\n A prolonged fasting period interrupted with oral ISE administration resulted in an RGV of low risk, without counterbalancing a potential fasting-induced hypoglycemia." ]

[ "19057612", "12042546", "20947097" ]

[ "Treatment of MAS with PPHN using combined therapy: SLL, bolus surfactant and iNO.", "A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome.", "Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome." ]

[ "The objective of the study was to compare the effectiveness of surfactant treatment either by bolus or surfactant lung lavage followed by inhaled nitric oxide (iNO) therapy in infants with meconium aspiration syndrome (MAS) complicated by persistent pulmonary hypertension (PPHN). In this study, thirteen infants with diagnosis of MAS and PPHN were first treated with conventional respiratory support. Then between 2 and 22h of life they were randomized either to bolus surfactant treatment (n=6) or surfactant lung lavage (SLL, n=7) treatment. Then all infants were treated with iNO therapy. The groups were compared with regard to their clinical course: changes in PaO(2), FiO(2), MAP, OI, A-a oxygen gradient, duration of iNO therapy, length of ventilation and hospitalization. Complications and mortality were also compared. The results showed that infants treated with SLL had significant improvements in oxygenation, decreases in MAP and A-a gradients. But there were no significant differences in duration of ventilation, iNO treatment, length of hospitalization or complications. In conclusion these data show no advantage of SLL therapy over bolus surfactant treatment in infants with MAS complicated by PPHN.", "Infants with meconium aspiration syndrome (MAS) have marked surfactant dysfunction. Airways and alveoli of affected neonates contain meconium, inflammatory cells, inflammatory mediators, edema fluid, protein, and other debris. The objective of this study was to compare treatment with bronchoalveolar lavage using dilute Surfaxin with standard therapy in a population of newborn infants with MAS.\n Inclusion criteria were 1) gestational age > or =35 weeks, 2) enrollment within 72 hours of birth, 3) diagnosis of MAS, 4) need for mechanical ventilation, and 5) an oxygenation index > or =8 and < or =25. Subjects were randomized to either lavage with Surfaxin or standard care (2:1 proportion). In lavaged infants, a volume of 8 mL/kg dilute Surfaxin (2.5 mg/mL) was instilled into each lung over approximately 20 seconds followed by suctioning after 5 ventilator breaths. The procedure was repeated twice. The third and final lavage was with a more concentrated solution (10 mg/mL) of Surfaxin.\n Twenty-two infants were enrolled (15 Surfaxin and 7 control). Demographic characteristics were similar. There were trends (not significant) for Surfaxin-lavaged infants to be weaned from mechanical ventilation earlier (mean of 6.3 vs 9.9 days, respectively), as well as to have a more rapid decline in their oxygenation indexes compared with control infants, the latter difference persisting for the 96-hour-long study period. The therapy was safe and generally well tolerated by the infants.\n Dilute Surfaxin lavage seems to be a safe and potentially effective therapy in the treatment of MAS. Data from this investigation support future prospective, controlled clinical trials of bronchoalveolar lavage with Surfaxin in neonates with MAS.", "To evaluate whether lung lavage with surfactant changes the duration of mechanical respiratory support or other outcomes in meconium aspiration syndrome (MAS).\n We conducted a randomized controlled trial that enrolled ventilated infants with MAS. Infants randomized to lavage received two 15-mL/kg aliquots of dilute bovine surfactant instilled into, and recovered from, the lung. Control subjects received standard care, which in both groups included high frequency ventilation, nitric oxide, and, where available, extracorporeal membrane oxygenation (ECMO).\n Sixty-six infants were randomized, with one ineligible infant excluded from analysis. Median duration of respiratory support was similar in infants who underwent lavage and control subjects (5.5 versus 6.0 days, P = .77). Requirement for high frequency ventilation and nitric oxide did not differ between the groups. Fewer infants who underwent lavage died or required ECMO: 10% (3/30) compared with 31% (11/35) in the control group (odds ratio, 0.24; 95% confidence interval, 0.060-0.97). Lavage transiently reduced oxygen saturation without substantial heart rate or blood pressure alterations. Mean airway pressure was more rapidly weaned in the lavage group after randomization.\n Lung lavage with dilute surfactant does not alter duration of respiratory support, but may reduce mortality, especially in units not offering ECMO.\n Copyright © 2011 Mosby, Inc. All rights reserved." ]

[ "19298950" ]

[ "Corneal wavefront errors 24 months after deep lamellar endothelial keratoplasty and penetrating keratoplasty." ]

[ "To evaluate high-order aberrations (HOA) induced by the anterior corneal surface after deep lamellar endothelial keratoplasty (DLEK) and penetrating keratoplasty (PK).\n Prospective, randomized clinical trial.\n Twenty-eight eyes of 25 patients with corneal edema resulting from Fuchs dystrophy underwent DLEK with a 9- to 10-mm incision (n = 13) or PK with double-running sutures (n = 15) at the Cornea Service, Mayo Clinic Department of Ophthalmology, Rochester, Minnesota. The main outcome measures were HOA from the anterior corneal surface calculated from corneal topography and decomposed into Zernike polynomials to the sixth order, high- and low-contrast visual acuity (VA), and contrast sensitivity. Variables after surgery were compared with those before surgery and between treatments by using generalized estimating equation models with Bonferroni adjustment.\n Total HOA through 24 months (0.48 +/- 0.15 microm) after DLEK was similar to total aberration before surgery (0.44 +/- 0.23 microm; P = .10). After PK, total HOA remained elevated through 24 months (1.68 +/- 0.58 microm) compared with that before surgery (0.49 +/- 0.27 microm; P < .005) and compared with that after DLEK (P < .006). At 24 months after PK, corneas with sutures removed had greater total HOAs than corneas with sutures intact (1.90 +/- 0.52 microm vs 1.18 +/- 0.33 microm; P = .001). High- and low-contrast VA and contrast sensitivity at 24 months after PK did not correlate with any HOA.\n HOAs from the anterior corneal surface were higher after PK compared with after DLEK but did not correlate with visual function after PK." ]

[ "11114313", "11023504", "11588025", "8676625" ]

[ "Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia.", "Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial.", "Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients.", "Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukaemia. The French Cooperative Group on CLL." ]

[ "Fludarabine is an effective treatment for chronic lymphocytic leukemia that does not respond to initial treatment with chlorambucil. We compared the efficacy of fludarabine with that of chlorambucil in the primary treatment of chronic lymphocytic leukemia.\n Between 1990 and 1994, we randomly assigned 509 previously untreated patients with chronic lymphocytic leukemia to one of the following treatments: fludarabine (25 mg per square meter of body-surface area, administered intravenously daily for 5 days every 28 days), chlorambucil (40 mg per square meter, given orally every 28 days), or fludarabine (20 mg per square meter per day for 5 days every 28 days) plus chlorambucil (20 mg per square meter every 28 days). Patients with an additional response at each monthly evaluation continued to receive the assigned treatment for a maximum of 12 cycles.\n Assignment of patients to the fludarabine-plus-chlorambucil group was stopped when a planned interim analysis revealed excessive toxicity and a response rate that was not better than the rate with fludarabine alone. Among the other two groups, the response rate was significantly higher for fludarabine alone than for chlorambucil alone. Among 170 patients treated with fludarabine, 20 percent had a complete remission, and 43 percent had a partial remission. The corresponding values for 181 patients treated with chlorambucil were 4 percent and 33 percent (P< 0.001 for both comparisons). The median duration of remission and the median progression-free survival in the fludarabine group were 25 months and 20 months, respectively, whereas both values were 14 months in the chlorambucil group (P<0.001 for both comparisons). The median overall survival among patients treated with fludarabine was 66 months, which was not significantly different from the overall survival in the other two groups (56 months with chlorambucil and 55 months with combined treatment). Severe infections and neutropenia were more frequent with fludarabine than with chlorambucil (P=0.08), although, overall, toxic effects were tolerable with the two single-drug regimens.\n When used as the initial treatment for chronic lymphocytic leukemia, fludarabine yields higher response rates and a longer duration of remission and progression-free survival than chlorambucil.", "The efficacy and toxicity of cladribine (2-CdA) + prednisone (P) versus chlorambucil (Chl) + P were compared in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia (CLL) in a randomized, multicenter prospective trial. Eligible patients were assigned to either 2-CdA 0.12 mg/kg per day in 2-hour infusions and P 30 mg/m(2) per day for 5 consecutive days or Chl 12 mg/m(2) per day and P 30 mg/m(2) per day for 7 consecutive days. Three courses were administered at 28-day intervals or longer if myelosuppression developed. The therapy was finished if complete response (CR) was achieved. Of 229 available patients 126 received 2-CdA+P and 103 received Chl+P as a first-line treatment. CR and overall response rates were significantly higher in the patients treated with 2-CdA+P (47% and 87%, respectively) than in the patients treated with Chl+P (12% and 57%, respectively) (P = .001). Progression-free survival was significantly longer in the 2-CdA-treated group (P = .01), but event-free survival was not statistically different. Thirteen percent of patients were refractory to 2-CdA+P and 43% to Chl+P (P = .001). Drug-induced neutropenia was more frequently observed during 2-CdA+P (23%) than Chl+P therapy (11%) (P = .02), but thrombocytopenia occurred with similar frequency in both groups (36% and 27%, respectively). Infections were seen more frequently in the 2-CdA+P-treated group (56%) than in the Chl+P-treated group (40%; P = .02). Death rates have so far been similar in patients treated with 2-CdA (20%) and with Chl (17%). The probability of overall survival calculated from Kaplan-Meier curves at 24 months was also similar for both groups (78% and 82%, respectively). (Blood. 2000;96:2723-2729)", "To comparatively assess first-line treatment with fludarabine and 2 anthracycline-containing regimens, namely CAP (cyclophosphamide, doxorubicin plus prednisone) and ChOP (cyclophosphamide, vincristine, prednisone plus doxorubicin), in advanced stages of chronic lymphocytic leukemia (CLL), previously untreated patients with stage B or C CLL were randomly allocated to receive 6 monthly courses of either ChOP, CAP, or fludarabine (FAMP), stratified based on the Binet stages. End points were overall survival, treatment response, and tolerance. From June 1, 1990 to April 15, 1998, 938 patients (651 stage B and 287 stage C) were randomized in 73 centers. Compared to ChOP and FAMP, CAP induced lower overall remission rates (58.2%; ChOP, 71.5%; FAMP; 71.1%; P <.0001 for each), including lower clinical remission rates (CAP, 15.2%; ChOP, 29.6%; FAMP, 40.1%; P =.003). By contrast, median survival time did not differ significantly according to randomization (67, 70, and 69 months in the ChOP, CAP, and FAMP groups, respectively). Incidences of infections (< 5%) and autoimmune hemolytic anemia (< 2%) during the 6 courses were similar in the randomized groups, whereas fludarabine induced, compared to ChOP and CAP, more frequent protracted thrombocytopenia (P =.003) and less frequent nausea-vomiting (P =.003) and hair loss (P <.0001). For patients with stage B and C CLL first-line fludarabine and ChOP regimens both provided similar overall survival and close response rates, and better results than CAP. However, there was an increase in clinical remission rate and a trend toward a better tolerance of fludarabine over ChOP that may influence the choice between these regimens as front-line treatments in patients with CLL.", "Fludarabine seems to be a promising treatment for patients with advanced chronic lymphocytic leukaemia (CLL). We compared fludarabine therapy with the combination of cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of CLL in a randomised, multicentre prospective trial.\n Patients older than 18 years of age were entered into the study if they presented with previously untreated B-cell lineage CLL (B-CLL) of Binet stages B or C or relapsed B-CLL pretreated with chorambucil or similar non-anthracycline-containing regimens. Patients were randomly assigned to either fludarabine (25 mg/m2 per day on days 1-5) or CAP (cyclophosphamide 750 mg/m2 per day and doxorubicin 50 mg/m2 per day on day 1, and prednisone 40 mg/m2 per day on days 1-5), both given for six courses.\n Of 196 evaluable patients, 100 were previously untreated whereas 96 patients had received prior therapy. Remission rates were significantly higher after fludarabine than CAP, with overall response rates of 60% and 44%, respectively (p = 0.023). A higher response rate to fludarabine was observed in both untreated (71% vs 60%, p = 0.26) and pretreated (48% vs 27%, p = 0.036) cases, although the difference was statistically significant only in pretreated cases. In the latter group, remission duration and survival did not differ between treatment groups with a median remission duration of 324 days after fludarabine and 179 days after CAP (p = 0.22) and median survival times of 728 days and 731 days, respectively. In untreated cases, on the other hand, fludarabine induced significantly longer remissions than CAP with the median not yet reached after fludarabine and a median of 208 days after CAP (p < 0.001). This effect also translated into a tendency towards longer overall survival after fludarabine (p = 0.087). Treatment-associated side-effects consisted in both regimens of predominantly myelosuppression and in particular granulocytopenia. CAP-treated patients had a higher frequency and severity of nausea and vomiting (25% vs 5%, p < 0.001) and alopecia (65% vs 2%, p < 0.001).\n Fludarabine provided an effective and well-tolerated therapy for patients with advanced CLL, which compared favourably with CAP as one of the most effective standard regimens. In second-line therapy, fludarabine induced a significantly higher rate of complete and partial remissions, while in first-line therapy a significant prolongation of remission was obtained, which may translate into an improvement of overall survival." ]

[ "8348504", "20034729", "15948743", "9119635", "8692531" ]

[ "Intravesical 4'-epi-doxorubicin (epirubicin) versus bacillus Calmette-Guérin. A controlled prospective study on the prophylaxis of superficial bladder cancer.", "Long-term efficacy results of EORTC genito-urinary group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guérin, and bacillus Calmette-Guérin plus isoniazid in patients with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder.", "Twelve-year follow up of a randomized prospective trial comparing bacillus Calmette-Guerin and epirubicin as adjuvant therapy in superficial bladder cancer.", "BCG versus epirubicin in the prophylaxis of multiple superficial bladder tumours: results of a prospective randomized study using modified treatment schemes.", "Intravesical bacillus Calmette-Guérin versus epirubicin in the prophylaxis of recurrent and/or multiple superficial bladder tumours." ]

[ "The selection of the most appropriate antineoplastic agent and optimal treatment schedule for the prophylaxis of superficial bladder cancer against tumor recurrences is the subject of continual investigations.\n A controlled prospective trial involving 161 patients evaluated and compared the efficacy of intravesical epirubicin and bacillus Calmette-Guérin (BCG) administration as prophylaxis against recurrences after complete transurethral resection of superficial bladder cancer. The treatment schedule, consisting of one 6- or 8-week course of instillations (50 mg epirubicin or 150 mg BCG per instillation) followed by single maintenance doses to the responders at follow-up examinations, was modified for those of the initial responders who were at high risk for recurrence and who received an additional separate 4-week course of treatment 6 months after the start of therapy.\n Sixty percent of the patients treated with epirubicin, 68% of the patients treated with BCG, and 41% of the control subjects, who underwent resection only, remained free of recurrences for a mean follow-up of 32.9 months. The only significant difference was found between patients treated with BCG and control subjects, in favor of the former. Conversely, recurrence rate per 100 patient-months and mean interval to recurrence showed both drugs to be superior to resection alone regarding several tumor characteristics. However, a significant benefit in favor of BCG when compared with epirubicin was shown in those patients who had Stage T1 and Grade 3 tumors at presentation.\n Intravesical epirubicin and BCG were superior to transurethral resection alone in the prophylaxis of superficial bladder cancer, but with respect to superficially invasive and high-grade tumors, BCG demonstrated a remarkable advantage.", "Intravesical chemotherapy and bacillus Calmette-Guérin (BCG) reduce the recurrence rate in patients with stage Ta T1 urothelial bladder cancer; however, the benefit of BCG relative to chemotherapy for long-term end points is controversial, especially in intermediate-risk patients.\n The aim of the study was to compare the long-term efficacy of BCG and epirubicin.\n From January 1992 to February 1997, 957 patients with intermediate- or high-risk stage Ta T1 urothelial bladder cancer were randomized after transurethral resection to one of three treatment groups in the European Organization for Research and Treatment of Cancer Genito-Urinary Group phase 3 trial 30911.\n Patients received six weekly instillations of epirubicin, BCG, or BCG plus isoniazid (INH) followed by three weekly maintenance instillations at months 3, 6, 12, 18, 24, 30, and 36.\n End points were time to recurrence, progression, distant metastases, overall survival, and disease-specific survival.\n With 837 eligible patients and a median follow-up of 9.2 yr, time to first recurrence (p<0.001), distant metastases (p=0.046), overall survival (p=0.023), and disease-specific survival (p=0.026) were significantly longer in the two BCG arms combined as compared with epirubicin; however, there was no difference for progression. Three hundred twenty-three patients with stage T1 or grade 3 tumors were high risk, and the remaining 497 patients were intermediate risk. The observed treatment benefit was at least as large, if not larger, in the intermediate-risk patients compared with the high-risk patients.\n In patients with intermediate- and high-risk stage Ta and T1 urothelial bladder cancer, intravesical BCG with or without INH is superior to intravesical epirubicin not only for time to first recurrence but also for time to distant metastases, overall survival, and disease-specific survival. The benefit of BCG is not limited to just high-risk patients; intermediate-risk patients also benefit from BCG.\n This study was registered with the US National Cancer Institute clinical trials database [protocol ID: EORTC-30911]. http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=77075&version=HealthProfessional&protocolsearchid=6540260.\n Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.", "To compare bacillus Calmette-Guerin (BCG) with epirubicin in adjuvant therapy of superficial bladder transitional cell carcinoma, with respect to recurrence, progression and survival. Prognostic factors are also evaluated.\n Between October 1991 and September 1999, all patients harboring superficial bladder cancers (Ta or T1) with any of the relevant criteria (stage>a, grade>1, size>1 cm, multiple or recurrent tumors), after complete transurethral resection were randomized to receive either 81 mg Connaught strain BCG or 50 mg epirubicin. Patients with recurrences were eligible to crossover, even repeatedly, until progression. Recurrence, progression and survival were analyzed in relation to initial treatment, patient characteristics and tumor characteristics.\n There were 209 patients included in the study, 149 men and 60 women. The mean age was 69.9 years (range, 24-92). The BCG group consisted of 102 patients and the epirubicin group contained 107 patients. Final analysis was made at a median follow up of 23, 47 and 61 months for recurrence, progression and survival, respectively. The 10-year Kaplan-Meier estimates for recurrence-free, progression-free and disease-specific survival were 61%, 78% and 80%, respectively, for the BCG group. The corresponding figures were 32%, 74% and 92%, respectively, for the epirubicin group. Time to recurrence differed significantly between two treatment groups (P=0.0004). Multiplicity increased the risk of recurrence, while grading influenced recurrence, progression and disease specific survival.\n Bacillus Calmette-Guerin prolonged time to recurrence when compared with epirubicin. Grading was shown to be a universal prognostic factor for recurrence, progression and disease specific survival.", "A prospective randomized trial on 94 eligible patients evaluated and compared the efficacy of adjuvant intravesical epirubicin and bacillus Calmette-Guérin (BCG) after complete resection of multifocal superficial bladder cancer. BCG treatment schedule consisted of an induction 6-week course of instillations (150 mg Pasteur BCG per instillation) and single maintenance doses to patients who remained free of recurrences at follow-up examinations for a total treatment period of 2 years. These initial responders received additionally a separate 4-week course of therapy 6 months after the start of treatment. Chemoprophylaxis included an early (on the second postoperative day) instillation followed by 4 weekly treatments with epirubicin (50 mg per instillation) and then by 10 monthly treatments for the initial responders during the first year of follow-up and at every follow-up examination for a total treatment period of 2 years. The overall treatment results did not differ significantly between the 2 arms (54% of patients of the epirubicin group remained free of recurrences compared to 65% of those treated with BCG) for an identical mean follow-up of 35.1 months. However, a significant benefit in favour of BCG when compared with epirubicin was shown in patients who had stage T1 and grade 3 tumours and in terms of relative risk of recurrences, disease-free interval and recurrence rate per 100 patient-months. Both drugs were proved to be safe with manageable toxicity.", "A prospective, randomized trial was conducted to evaluate and compare the effects of modified adjuvant intravesical bacillus Calmette-Guérin (BCG) and epirubicin regimens in patients with superficial bladder cancer. One hundred thirty-two individuals with recurrent and/or multiple neoplasms, i.e. at high risk for tumour recurrence and progression, were enrolled. After complete transurethral resection of their tumours, the patients received a 6-week course of BCG instillations or an early 4-week course of epirubicin instillations as their initial therapy. Those with stage Ta and grade 1 neoplasms who remained free of recurrences received maintenance therapy consisting of single quarterly instillations. However, for those with stage T1 cancer of any grade or stage Ta of grade 2 or 3 neoplasms who also remained free of recurrences, the treatment schedules were modified: they received, instead of single maintenance doses, 3 weekly instillations of epirubicin at months 3 and 6 of follow-up, or a 3-week course of BCG at month 6 of follow-up. The recurrence-free rates did not differ significantly between the two study groups (44% for epirubicin versus 55% for BCG), for an identical median follow-up of 43 months. However, in terms of relative risk of recurrences, disease-free intervals and recurrence rate per 100 patient-months, a significant benefit in favour of BCG when compared with epirubicin was demonstrated in patients who had stage T1 or grade 3 neoplasms." ]

[ "1870651", "8913991", "12084137", "9811084", "12127464", "15387206", "15265098", "15301659" ]

[ "A randomized trial of treatment options for alcohol-abusing workers.", "Issues in the implementation of a randomized clinical trial that includes Alcoholics Anonymous: studying AA-related behaviors during treatment.", "Process and outcome changes with relapse prevention versus 12-Step aftercare programs for substance abusers.", "Matching alcoholism treatments to client heterogeneity: treatment main effects and matching effects on drinking during treatment. Project MATCH Research Group.", "A trial of \"standard\" outpatient alcoholism treatment vs. a minimal treatment control.", "What is Alcoholics Anonymous affiliation?", "In 12-step groups, helping helps the helper.", "Motivational enhancement for 12-step involvement among patients undergoing alcohol detoxification." ]

[ "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 purpose of this study is to examine implementation of a randomized clinical trial and within treatment behavior when AA is included as an element of treatment. Special attention is given to the measurement of compliance, use of treatment skills, and the nature and extent of involvement with AA during the active phase of treatment.\n Subjects, 90 male alcoholics and their female partners seeking conjoint, outpatient behavioral alcoholism treatment, were randomly assigned to one of three treatments: alcohol-focused behavioral marital therapy (ABMT), ABMT plus AA/Alanon (AA/ABMT), or ABMT plus relapse prevention (RP/ABMT). Within treatment data are reported for the 68 couples who completed at least five treatment sessions. Measures included: treatment attrition, number of treatment sessions, attendance at AA and Alanon, use of AA and Alanon skills, compliance with homework assignments and drinking during treatment.\n Several aspects of within treatment behavior were examined: (1) Attrition: There was no differential attrition across treatment conditions, with 24.4% of couples discontinuing treatment prior to the fifth session. (2) AA and Alanon attendance: Subjects in the AA/ABMT treatment were more likely to attend AA (91.7% attended at least one AA meeting; 58.3% attended at least one Alanon meeting) than were subjects in the other treatment conditions (18% attended at least one AA meeting and 14% at least one Alanon meeting). Subjects in the AA/ABMT condition attended significantly more AA and Alanon meetings than did subjects in the other treatment conditions. (3) Homework compliance: Subjects generally showed no differences in compliance with homework assignments, but spouses in the AA/ABMT condition completed less condition-specific homework (37.2%, versus 67.8% for the RP/ABMT spouses) because of low utilization of Alanon. (4) Use of AA-related skills: Subjects reported using AA-related skills more frequently in the AA/ABMT condition than in the other treatment conditions. (5) Patterns of attendance: Analyses of AA attendance during treatment revealed three patterns: positive attendance, characterized by regular AA attendance or increasing use of AA across treatment; negative attendance, characterized by decreased AA attendance over time; and nonattendance, characterized by none or infrequent and erratic attendance.\n Randomized clinical trials can be used to study AA. Use of multiple measures of treatment compliance and examination of patterns of AA utilization use over time provide more complex views of the patterns of involvement with AA than do simple descriptive reports of attendance.", "Presumptive support was sought for mechanisms of action whereby two conceptually distinct aftercare programs, relapse prevention (RP) and 12-Step facilitation (TSF), impact upon substance abusers.\n Adults who had just completed intensive treatment were assigned randomly to either RP (n=61) or TSF (n=70) aftercare programs.\n Three residential treatment facilities.\n Trained counselors delivered to small groups a manualized aftercare program which focused either upon the utilization of cognitive-behavioral processes to orchestrate change through an individualized treatment plan (i.e. RP) or which sought to facilitate utilization of AA's 12 Steps (i.e. TSF).\n Process measures developed specifically to quantify either: (a) the changes in self-efficacy process in RP or (b) the utilization of AA's principles in TSF, as well as psychosocial and substance abuse indices were administered to all patients pre- and post-aftercare and at 6-month follow-up.\n A significant relationship between changes in measures of self- efficacy for RP participants as well as a trend for a relationship between process-specific change for TSF participants partially satisfied the first condition for presumptive support. The fact that the intervention-specific mediators covaried with several outcome indices, and that removal of such mediators attenuated prediction of outcome met, respectively, the second and third conditions for presumptive support.\n Carefully orchestrated RP and TSF aftercare programs yield process changes that are related positively to improved outcome.", "This article examines client drinking and related psychosocial functioning during the course of alcoholism treatment. It focuses on (1) the main effects of the three Project MATCH treatments, (2) the prognostic value of client attributes employed in the matching hypotheses, and (3) the attribute by treatment interaction effects.\n Clients recruited from outpatient settings (n = 952) or from aftercare settings (n = 774) were randomized to one of the following treatments: Motivational Enhancement Therapy (MET), Cognitive Behavioral Therapy (CBT) and Twelve-Step Facilitation (TSF). Alcohol consumption and psychosocial functioning during treatment were assessed at the end of the 12-week treatment phase.\n During the treatment phase, small but statistically significant differences among treatments were found only in the outpatient arm on measures of alcohol consumption and alcohol-related negative consequences. Forty-one percent (41%) of CBT and TSF clients were abstinent or drank moderately without alcohol-related consequences, compared with 28% of MET clients. Tests of 10 a priori primary client-treatment matching hypotheses failed to find any interaction effects that had an impact on drinking throughout the treatment phase.\n In the outpatient setting there appears to be a temporary advantage to assigning individuals to CBT or TSF rather than MET. When there is a need to quickly reduce heavy drinking and alcohol-related consequences, it appears that CBT or TSF should be the treatment of choice.", "This study sought to examine the effectiveness of a \"standard\" outpatient alcoholism treatment (ST) program. An outpatient alcoholism treatment as it is commonly practiced in the US (with group and individual therapy, and an emphasis on Alcoholics Anonymous [AA]), was compared with a minimal treatment (MT) approach (weekly alcohol education movies). At 6 months, ST patients surpassed those in MT in terms of complete abstinence, reduction in amount of alcohol consumed, length of sobriety at follow-up, improvement in employment status, number of AA meetings attended, and lower initial drop-out. It is concluded that a ST approach is more helpful than MT in treating severely alcohol-dependent individuals who have not been able to cut down drinking on their own. Those already drinking less appeared to be helped by MT.", "An increasing body of research evidence supports the use of 12-step program affiliation as an effective adjunct and aftercare for formal treatment. Recently, three brief (9- or 10-item) measures of affiliation have been developed. However, the brief scales are difficult to interpret, and the question of exactly what is affiliation (or disaffiliation) remains unclear. This analysis examines the question of what is the essence of affiliation vs. disaffiliation. Data from the Project MATCH 1-year posttreatment Alcoholics Anonymous Involvement (AAI) scale (N=1506) are used to identify the most salient items of Alcoholics Anonymous (AA) affiliation predicting 1-year posttreatment drinking outcomes. Analysis using stepwise regression suggests that a three-item solution can explain a similar amount of variance in the proportion of days abstinent in months 9 through 12 posttreatment, as does using the nine items. These three \"core items predicting recovery\" include AA attendance, sum of steps completed, and identifying self as an AA member. As an affiliation composite scale, these three items are easier to interpret and administer than the full AAI scale, and when combined, possess adequate reliability (alpha=0.72).", "The helper therapy principle suggests that, within mutual-help groups, those who help others help themselves. The current study examines whether clients in treatment for alcohol and drug problems benefit from helping others, and how helping relates to 12-step involvement.\n Longitudinal treatment outcome.\n An ethnically diverse community sample of 279 alcohol- and/or drug-dependent individuals (162 males, 117 females) was recruited through advertisement and treatment referral from Northern California Bay Area communities.\n were treated at one of four day-treatment programs.\n A helping checklist measured the amount of time participants spent, during treatment, helping others by sharing experiences, explaining how to get help and giving advice on housing and employment. Measures of 12-step involvement and substance use outcomes were administered at baseline and a 6 month follow-up.\n Helping and 12-step involvement emerged as important and related predictors of treatment outcomes. In the general sample, total abstinence at follow-up was strongly and positively predicted by 12-step involvement at follow-up, but not by helping during treatment; still, helping positively predicted subsequent 12-step involvement. Among individuals still drinking at follow-up, helping during treatment predicted a lower probability of binge drinking, whereas effects for 12-step involvement proved inconsistent.\n Findings support the helper therapy principle and clarify the process of 12-step affiliation.", "Forty-eight patients undergoing inpatient detoxification for alcohol dependence were assigned to either brief advice (BA) to attend Alcoholics Anonymous or a motivational enhancement for 12-step involvement (ME-12) intervention that focused on increasing involvement in 12-step self-help groups. Attendance at 12-step groups did not differ significantly by treatment condition over 6 months of follow-up, nor did drinking outcomes. There was a significant interaction between 12-step experience and treatment condition, indicating that ME-12 was associated with relatively better alcohol outcomes at the low ends of 12-step experience, whereas BA was associated with relatively better outcomes at the high ends of 12-step experience. Results indicate that among patients undergoing alcohol detoxification, ME-12 may be beneficial only for those who have little experience with 12-step groups." ]

[ "19685848", "15319761", "2141951", "19940729", "15611489", "9761803", "146394", "4274488", "9762745", "9883955", "17993364", "8423429", "6210835", "18775942", "16540864", "19425461" ]

[ "Comparison of short-term response to two spinal manipulation techniques for patients with low back pain in a military beneficiary population.", "A randomized clinical trial comparing chiropractic adjustments to muscle relaxants for subacute low back pain.", "An open controlled assessment of osteopathic manipulation in nonspecific low-back pain.", "Comparison of the effectiveness of three manual physical therapy techniques in a subgroup of patients with low back pain who satisfy a clinical prediction rule: a randomized clinical trial.", "A clinical prediction rule to identify patients with low back pain most likely to benefit from spinal manipulation: a validation study.", "A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low back pain.", "Acute low back pain in industry. A controlled prospective study with special reference to therapy and confounding factors.", "Back pain: a randomized clinical trial of rotational manipulation of the trunk.", "One-year follow-up comparison of the cost and effectiveness of chiropractic and physiotherapy as primary management for back pain. Subgroup analysis, recurrence, and additional health care utilization.", "Conservative treatment in patients sick-listed for acute low-back pain: a prospective randomised study with 12 months' follow-up.", "Assessment of diclofenac or spinal manipulative therapy, or both, in addition to recommended first-line treatment for acute low back pain: a randomised controlled trial.", "The Hmax/Mmax ratio as an outcome measure for acute low back pain.", "Acute low back pain. Comparison of two conservative treatment approaches.", "A randomised controlled trial of spinal manipulative therapy in acute low back pain.", "Identifying subgroups of patients with acute/subacute \"nonspecific\" low back pain: results of a randomized clinical trial.", "Manipulative therapy and clinical prediction criteria in treatment of acute nonspecific low back pain." ]

[ "To determine whether military health care beneficiaries with low back pain (LBP) who are likely to respond successfully to spinal manipulation experience a difference in short-term clinical outcomes based on the manipulation technique that is used.\n Sixty patients with LBP identified as likely responders to manipulation underwent a standardized clinical examination and were randomized to receive a lumbopelvic (LP) or lumbar neutral gap (NG) manipulation technique. Outcome measures were a numeric pain rating scale and the modified Oswestry Disability Questionnaire.\n Both the LP and NG groups experienced statistically significant reductions in pain and disability at 48 hours postmanipulation. The improvements seen in each group were small because of the short follow-up. There were no statistically significant or clinically meaningful differences in pain or disability between the two groups.\n The two manipulation techniques used in this study were equally effective at reducing pain and disability when compared at 48 hours posttreatment. Clinicians may employ either technique for the treatment of LBP and can expect similar outcomes in those who satisfy the clinical prediction rule (CPR). Further research is required to determine whether differences exist at longer-term follow-up periods, after multiple treatment sessions, or in different clinical populations.", "The adult lifetime incidence for low back pain is 75% to 85% in the United States. Investigating appropriate care has proven difficult, since, in general, acute pain subsides spontaneously and chronic pain is resistant to intervention. Subacute back pain has been rarely studied.\n To compare the relative efficacy of chiropractic adjustments with muscle relaxants and placebo/sham for subacute low back pain.\n A randomized, double-blind clinical trial.\n Subjects (N = 192) experiencing low back pain of 2 to 6 weeks' duration were randomly allocated to 3 groups with interventions applied over 2 weeks. Interventions were either chiropractic adjustments with placebo medicine, muscle relaxants with sham adjustments, or placebo medicine with sham adjustments. Visual Analog Scale for Pain, Oswestry Disability Questionnaire, and Modified Zung Depression Scale were assessed at baseline, 2 weeks, and 4 weeks. Schober's flexibility test, acetaminophen usage, and Global Impression of Severity Scale (GIS), a physician's clinical impression used as a secondary outcome, were assessed at baseline and 2 weeks.\n Baseline values, except GIS, were similar for all groups. When all subjects completing the protocol were combined (N = 146), the data revealed pain, disability, depression, and GIS decreased significantly (P <.0001); lumbar flexibility did not change. Statistical differences across groups were seen for pain, a primary outcome, (chiropractic group improved more than control group) and GIS (chiropractic group improved more than other groups). No significant differences were seen for disability, depression, flexibility, or acetaminophen usage across groups.\n Chiropractic was more beneficial than placebo in reducing pain and more beneficial than either placebo or muscle relaxants in reducing GIS.", "An open controlled pilot trial on nonspecific low-back pain sufferers demonstrated responsiveness to osteopathic manipulation of some patients presenting with pain durations of 14 to 28 days. No response was demonstrated in those with shorter episodes at presentation. The advantage to manipulated patients was maximal between 1 and 2 weeks after commencing treatment, but was not discernable after 4 weeks. The demonstration of a similar responsive stratum by other investigators, with both teams totally unaware of each other's work during data collection, suggests a high degree of reliability for this finding.", "Randomized clinical trial.\n The purpose of this randomized clinical trial was to examine the generalizability of 3 different manual therapy techniques in a patient population with low back pain that satisfy a clinical prediction rule (CPR).\n Recently a CPR that identifies patients with LBP who are likely to respond rapidly and dramatically to thrust manipulation has been developed and validated. The generalizability of the CPR requires further investigation.\n A total of 112 patients were enrolled in the trial and provided demographic information and completed a number of self-report questionnaires including the Oswestry Disability Questionnaire (ODQ) and the Numerical Pain Rating Scale (NPRS) at baseline, 1-week, 4-weeks, and 6-months. Patients were randomly assigned to receive 1 of the 3 manual therapy techniques for 2 consecutive treatment sessions followed by exercise regimen for an additional 3 sessions. We examined the primary aim using a linear mixed model for repeated measures, using the ODQ and NPRS as dependent variables. The hypothesis of interest was the group by time interaction, which was further explored with pair-wise comparisons of the estimated marginal means.\n There was a significant group x time interaction for the ODQ (P < 0.001) and NPRS scores (P = 0.001). Pair-wise comparisons revealed no differences between the supine thrust manipulation and side-lying thrust manipulation at any follow-up period. Significant differences in the ODQ and NPRS existed at each follow-up between the thrust manipulation and the nonthrust manipulation groups at 1-week and 4-weeks. There was also a significant difference in ODQ scores at 6-months in favor of the thrust groups.\n The results of the study support the generalizability of the CPR to another thrust manipulation technique, but not to the nonthrust manipulation technique that was used in this study. In general, our results also provided support that the CPR can be generalized to different settings from which it was derived and validated. However, additional research is needed to examine this issue.", "Conflicting evidence exists about the effectiveness of spinal manipulation.\n To validate a manipulation clinical prediction rule.\n Multicenter randomized, controlled trial.\n Physical therapy clinics.\n 131 consecutive patients with low back pain, 18 to 60 years of age, who were referred to physical therapy.\n Patients were randomly assigned to receive manipulation plus exercise or exercise alone by a physical therapist for 4 weeks.\n Patients were examined according to the clinical prediction rule criteria (symptom duration, symptom location, fear-avoidance beliefs, lumbar mobility, and hip rotation range of motion). Disability and pain at 1 and 4 weeks and 6 months were assessed.\n Outcome from spinal manipulation depends on a patient's status on the prediction rule. Treatment effects are greatest for the subgroup of patients who were positive on the rule (at least 4 of 5 criteria met); health care utilization among this subgroup was decreased at 6 months. Compared with patients who were negative on the rule and received exercise, the odds of a successful outcome among patients who were positive on the rule and received manipulation were 60.8 (95% CI, 5.2 to 704.7). The odds were 2.4 (CI, 0.83 to 6.9) among patients who were negative on the rule and received manipulation and 1.0 (CI, 0.28 to 3.6) among patients who were positive on the rule and received exercise. A patient who was positive on the rule and received manipulation has a 92% chance of a successful outcome, with an associated number needed to treat for benefit at 4 weeks of 1.9 (CI, 1.4 to 3.5).\n The response rate for the 6-month follow-up resulted in inadequate power to detect statistically significant differences for some comparisons.\n The spinal manipulation clinical prediction rule can be used to improve decision making for patients with low back pain.", "There are few data on the relative effectiveness and costs of treatments for low back pain. We randomly assigned 321 adults with low back pain that persisted for seven days after a primary care visit to the McKenzie method of physical therapy, chiropractic manipulation, or a minimal intervention (provision of an educational booklet). Patients with sciatica were excluded. Physical therapy or chiropractic manipulation was provided for one month (the number of visits was determined by the practitioner but was limited to a maximum of nine); patients were followed for a total of two years. The bothersomeness of symptoms was measured on an 11-point scale, and the level of dysfunction was measured on the 24-point Roland Disability Scale.\n After adjustment for base-line differences, the chiropractic group had less severe symptoms than the booklet group at four weeks (P=0.02), and there was a trend toward less severe symptoms in the physical therapy group (P=0.06). However, these differences were small and not significant after transformations of the data to adjust for their non-normal distribution. Differences in the extent of dysfunction among the groups were small and approached significance only at one year, with greater dysfunction in the booklet group than in the other two groups (P=0.05). For all outcomes, there were no significant differences between the physical-therapy and chiropractic groups and no significant differences among the groups in the numbers of days of reduced activity or missed work or in recurrences of back pain. About 75 percent of the subjects in the therapy groups rated their care as very good or excellent, as compared with about 30 percent of the subjects in the booklet group (P<0.001). Over a two-year period, the mean costs of care were $437 for the physical-therapy group, $429 for the chiropractic group, and $153 for the booklet group.\n For patients with low back pain, the McKenzie method of physical therapy and chiropractic manipulation had similar effects and costs, and patients receiving these treatments had only marginally better outcomes than those receiving the minimal intervention of an educational booklet. Whether the limited benefits of these treatments are worth the additional costs is open to question.", "nan", "nan", "A randomized trial was conducted in which patients with back and neck pain, visiting a general practitioner, were allocated to chiropractic or physiotherapy.\n To compare outcome and costs of chiropractic and physiotherapy as primary treatment for patients with back and neck pain, with special reference to subgroups, recurrence rate, and additional health care use at follow-up evaluation 12 months after treatment.\n Earlier studies on the effect of spinal manipulation have shown inconsistent results. Mostly they include only short-term follow-up periods, and few cost-effectiveness analyses have been made.\n A group of 323 patients aged 18-60 years who had no contraindications to manipulation and who had not been treated within the previous month were included. Outcome measures were changes in Oswestry scores, pain intensity, and general health; recurrence rate; and direct and indirect costs.\n No differences were detected in health improvement, costs, or recurrence rate between the two groups. According to Oswestry score, chiropractic was more favorable for patients with a current pain episode of less than 1 week (5%) and physiotherapy for patients with a current pain episode of greater than 1 month (6.8%). Nearly 60% of the patients reported two or more recurrences. More patients in the chiropractic group (59%) than in the physiotherapy group (41%) sought additional health care. Costs varied considerably among individuals and subgroups; the direct costs were lower for physiotherapy in a few subgroups.\n Effectiveness and costs of chiropractic or physiotherapy as primary treatment were similar for the total population, but some differences were seen according to subgroups. Back problems often recurred, and additional health care was common. Implications of the result are that treatment policy and clinical decision models must consider subgroups and that the problem often is recurrent. Models must be implemented and tested.", "We evaluated three different conservative treatment methods for acute low-back pain patients in groups following a manual therapy programme, an intensive training programme, or a general practitioner programme, the latter serving as the control group. Patients aged 19-64 years on sick leave for low-back pain with or without sciatica were included in a prospective randomised study evaluating outcomes such as impairment, pain, functional disability, socio-economic disability and satisfaction with the treatment or explanations. Evaluation by unbiased observers was performed at 1, 3 and 12 months. The three treatment groups were comparable at baseline. With regard to satisfaction, the patients in the manual therapy programme and those in the intensive training programme were more satisfied with the treatment than those in the general practitioner programme at all follow-ups. With regard to the explanations of current low-back pain episodes, the patients in the manual therapy programme were more satisfied than those in the general practitioner programme at all follow-ups. The manual therapy programme group were also more satisfied with the explanations than those in the intensive training programme at the 1-month follow-up. However, no differences were revealed between the groups with respect to outcomes on measures of impairment, pain, functional disability or socioeconomic disability. All three study groups showed rapid improvement. After 1 month a significant improvement was noted in all outcome values compared with the values on entry to the study. Within the limitations discussed in our study, it is concluded that (1) patients sick listed with acute low-back pain, with or without sciatica, will be significantly improved after 1 month regardless of conservative treatment programme; (2) they will be more satisfied with the treatment if they are referred to a manual treatment programme or a training treatment programme; (3) they will be more satisfied with the explanations of the acute low-back problem if they are referred to one of the above groups, especially the manual treatment group; (4) they will not show any other differences with respect to subjective and objective variables, either at short-term or at long-term follow-ups.", "We aimed to investigate whether the addition of non-steroidal anti-inflammatory drugs or spinal manipulative therapy, or both, would result in faster recovery for patients with acute low back pain receiving recommended first-line care.\n 240 patients with acute low back pain who had seen their general practitioner and had been given advice and paracetamol were randomly allocated to one of four groups in our community-based study: diclofenac 50 mg twice daily and placebo manipulative therapy (n=60); spinal manipulative therapy and placebo drug (n=60); diclofenac 50 mg twice daily and spinal manipulative therapy (n=60); or double placebo (n=60). The primary outcome was days to recovery from pain assessed by survival curves (log-rank test) in an intention-to-treat analysis. This trial was registered with the Australian Clinical Trials Registry, ACTRN012605000036617.\n Neither diclofenac nor spinal manipulative therapy appreciably reduced the number of days until recovery compared with placebo drug or placebo manipulative therapy (diclofenac hazard ratio 1.09, 95% CI 0.84-1.42, p=0.516; spinal manipulative therapy hazard ratio 1.01, 95% CI 0.77-1.31, p=0.955). 237 patients (99%) either recovered or were censored 12 weeks after randomisation. 22 patients had possible adverse reactions including gastrointestinal disturbances, dizziness, and heart palpitations. Half of these patients were in the active diclofenac group, the other half were taking placebo. One patient taking active diclofenac had a suspected hypersensitivity reaction and ceased treatment.\n Patients with acute low back pain receiving recommended first-line care do not recover more quickly with the addition of diclofenac or spinal manipulative therapy.", "To evaluate the use of the Hmax/Mmax (H/M) ratio as an outcome measure for acute low back pain and to determine the change of this ratio in acute low back pain patients treated with spinal manipulation.\n Randomized clinical trial.\n Chiropractic college teaching clinic.\n Thirty-six patients with acute low back pain (pain of less than 2 wk duration) were referred by clinicians of the teaching clinic. Eligibility criteria for inclusion into the study consisted of the following: a score of eight or more on the Oswestry questionnaire, 33 mm or greater on a 100-mm visual analog scale, no involvement in litigation related to the low back pain complaint, patient not pregnant and no physical or electrodiagnostic signs of nerve root entrapment.\n The patients were randomly assigned to either a treatment or control group. The treatment group (n = 17) received treatment deemed appropriate by the clinician as long as it included a side-lying manipulation to the appropriate level. The control group (n = 19) received detuned ultrasound, application of a cold pack and 15-30 sec of very gentle soft tissue massage. Patients were treated three to five times over a period of 10 days and were subsequently reevaluated.\n The Hmax/Mmax ratio was calculated from the results of electrodiagnostic testing of the posterior tibial nerve. Extension/flexion ratio of the trunk musculature, Oswestry score and Visual Analog Scale score were also measured.\n The mean difference between H/M ratios pre- and postintervention for the group treated by chiropractic methods was -0.101 on the left and -0.117 on the right. The mean difference for the control group was 0.038 on the left and 0.036 on the right. Although not statistically significant, trends suggest that at the time of final assessment, the group receiving chiropractic care had improved more than the control group.\n The H/M ratio was found to be within normal limits in subjects with acute low back pain. The H/M ratio showed greater change in the group which received spinal manipulation, but the change was subtle. The results indicate that the H/M ratio may be of limited value in clinical practice.", "In a controlled clinical trial, we allocated 48 subjects with acute low back pain but without neurological signs, at random to two treatment groups. The conservative treatments compared were passive mobilisation and manipulation of the lumbar spine and a regimen of microwave diathermy, isometric abdominal exercises and ergonomic instructions. The duration of low back pain symptoms was significantly shorter for subjects receiving mobilisation and manipulation; they also achieved symptom-free status with fewer treatment sessions. While the duration of symptoms before first treatment, the treatment administered, and the pretest forward flexion movement indices accounted for 44% of the variance in the duration of symptoms, a stepwise multiple regression analysis showed that treatment is the most significant factor in predicting the length of time before a subject achieves symptom-free status.", "To determine whether treatment with spinal manipulative therapy (SMT) administered in addition to standard care is associated with clinically relevant early reductions in pain and analgesic consumption.\n 104 patients with acute low back pain were randomly assigned to SMT in addition to standard care (n = 52) or standard care alone (n = 52). Standard care consisted of general advice and paracetamol, diclofenac or dihydrocodeine as required. Other analgesic drugs or non-pharmacological treatments were not allowed. Primary outcomes were pain intensity assessed on the 11-point box scale (BS-11) and analgesic use based on diclofenac equivalence doses during days 1-14. An extended follow-up was performed at 6 months.\n Pain reductions were similar in experimental and control groups, with the lower limit of the 95% CI excluding a relevant benefit of SMT (difference 0.5 on the BS-11, 95% CI -0.2 to 1.2, p = 0.13). Analgesic consumptions were also similar (difference -18 mg diclofenac equivalents, 95% CI -43 mg to 7 mg, p = 0.17), with small initial differences diminishing over time. There were no differences between groups in any of the secondary outcomes and stratified analyses provided no evidence for potential benefits of SMT in specific patient groups. The extended follow-up showed similar patterns.\n SMT is unlikely to result in relevant early pain reduction in patients with acute low back pain.", "Randomized clinical trial.\n Compare outcomes of patients with low back pain receiving treatments matched or unmatched to their subgrouping based on initial clinical presentation.\n Patients with \"nonspecific\" low back pain are often viewed as a homogeneous group, equally likely to respond to any particular intervention. Others have proposed methods for subgrouping patients as a means for determining the treatment most likely to benefit patients with particular characteristics.\n Patients with low back pain of less than 90 days' duration referred to physical therapy were examined before treatment and classified into one of three subgroups based on the type of treatment believed most likely to benefit the patient (manipulation, stabilization exercise, or specific exercise). Patients were randomly assigned to receive manipulation, stabilization exercises, or specific exercise treatment during a 4-week treatment period. Disability was assessed in the short-term (4 weeks) and long-term (1 year) using the Oswestry. Comparisons were made between patients receiving treatment matched to their subgroup, versus those receiving unmatched treatment.\n A total of 123 patients participated (mean age, 37.7 +/- 10.7 years; 45% female). Patients receiving matched treatments experienced greater short- and long-term reductions in disability than those receiving unmatched treatments. After 4 weeks, the difference favoring the matched treatment group was 6.6 Oswestry points (95% CI, 0.70-12.5), and at long-term follow-up the difference was 8.3 points (95% CI, 2.5-14.1). Compliers-only analysis of long-term outcomes yielded a similar result.\n Nonspecific low back pain should not be viewed as a homogenous condition. Outcomes can be improved when subgrouping is used to guide treatment decision-making.", "Manipulative therapy as part of a multidimensional approach may be more effective than standard physical therapy in treating Acute Nonspecific Low Back Pain. 64 participants, 29 women and 35 men, with Acute Nonspecific Low Back Pain and a mean age of 40 yr. (SD=9.6) were randomly assigned to two groups: an experimental group (manipulative therapy plus physical therapy) and a control group (only physical therapy). A multicentre, nonblinded, randomised clinical trial was conducted. Pain relief was the main performance criteria measured together with secondary criteria which included functional status and mobility of the lower back. Fritz, Childs, and Flynn's clinical prediction rule--a duration of symptoms less than 16 days, no pain distal of the knee--was used to analyse the results. In combination with an age >35 years, results showed a statistical significant effect for disability, but no statistically significant benefit of additional manipulative therapy over physical therapy found for pain and mobility within 4 treatments. Controlled for the applied clinical prediction rule, there were statistically significant interaction effects with low effect size for disability and sex, but no significant effects were found for pain of mobility." ]

[ "9163613", "14711910" ]

[ "Low-dose aspirin in polycythaemia vera: a pilot study. Gruppo Italiano Studio Policitemia (GISP).", "Efficacy and safety of low-dose aspirin in polycythemia vera." ]

[ "In this pilot study, aimed at exploring the feasibility of a large-scale trial of low-dose aspirin in polycythaemia vera (PV), 112 PV patients (42 females, 70 males. aged 17-80 years) were selected for not having a clear indication for, or contraindication to, aspirin treatment and randomized to receive oral aspirin (40 mg/d) or placebo. Follow-up duration was 16 +/- 6 months. Measurements of thromboxane A2 production during whole blood clotting demonstrated complete inhibition of platelet cyclooxygenase activity in patients receiving aspirin. Aspirin administration was not associated with any bleeding complication. Within the limitations of the small sample size, this study indicates that a biochemically effective regimen of antiplatelet therapy is well tolerated in patients with polycythaemia vera and that a large-scale placebo-controlled trial is feasible.", "The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial.\n We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and no contraindication to such treatment in a double-blind, placebo-controlled, randomized trial to assess the safety and efficacy of prophylaxis with low-dose aspirin (100 mg daily). The two primary end points were the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The mean duration of follow-up was about three years.\n Treatment with aspirin, as compared with placebo, reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality were not reduced significantly. The incidence of major bleeding episodes was not significantly increased in the aspirin group (relative risk, 1.62; 95 percent confidence interval, 0.27 to 9.71).\n Low-dose aspirin can safely prevent thrombotic complications in patients with polycythemia vera who have no contraindications to such treatment.\n Copyright 2004 Massachusetts Medical Society" ]

[ "16418103", "11313839", "16970163" ]

[ "Effects of a new functional-sexological treatment for premature ejaculation.", "Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation.", "[Interventional effect of behaviour psychotherapy on patients with premature ejaculation]." ]

[ "Premature ejaculation is the most-prevalent sexual problem in men. Various treatments have been developed to increase control over the moment of ejaculation, with two of the most frequent techniques used in behavior therapy being the squeeze method developed by Masters and Johnson (1970) and the \"stop-and-start\" technique described by Semans (1956). These treatments are effective and improve matters in most cases. However, couples can be averse to using them, with some women reluctant to squeeze their partner's penis and some couples unwilling to interrupt sexual interaction once initiated. Under a new functional-sexological treatment intended to improve control over the moment of ejaculation, men learn how to control their arousal without having to interrupt sexual activity. In this study, we compared three groups of couples in which the man suffered from premature ejaculation. One followed the new functional-sexological treatment, another followed a behavioral treatment--including the squeeze and stop-and-start techniques--and a control group was placed on a waiting list. We used several questionnaires to assess the effects of the various treatments. Moreover, subjects provided an objective measure of duration of intercourse from penetration to ejaculation. These measures were taken pre- and posttreatment and at three-month follow-up. We ran analyses of variance to assess the effects of the treatments. Results indicate that the new treatment is very effective. We observed significant improvements in duration of intercourse, sexual satisfaction, and sexual functioning. The subjects in the behavioral treatment group obtained similar results. Furthermore, subjects from both groups were satisfied with their respective treatment.", "The objective was to compare the efficacy and safety of the as needed use of clomipramine, sertraline, paroxetine, sildenafil and the pause-squeeze technique in treatment of primary premature ejaculation. A prospective double blind randomized crossover study involving 31 patients was performed. Treatment phases comprised five 4-week consecutive treatment periods, each separated by a two-week washout period. Patients were randomly assigned to receive each of the 4 drugs and use pause-squeeze on an as needed basis. Drugs were administered 3 to 5 hours before anticipated coitus. Anxiety score and ejaculation latency time were measured before treatment, after each treatment, and during washout periods. Sexual satisfaction score was measured after each treatment. The median ejaculation latency time was significantly increased from the pretreatment median of 1 minute to 4 minutes, 3 minutes, 4 minutes, 15 minutes and 3 minutes during treatment with clomipramine, sertraline, paroxetine, sildenafil and pause-squeeze technique, respectively (all P 0.0001). Sildenafil was superior to other modalities in terms of ejaculation latency and satisfaction (P = 0.0001). The three antidepressants were comparable to each other in terms of efficacy (P > 0.05). Paroxetine was superior to the pause-squeeze technique in terms of efficacy (P < 0.05). In conclusion, sildenafil appears to be superior to other modalities and a valid alternative in treatment of premature ejaculation. The 3 antidepressants were equivalent to each other in terms of efficacy and safety. Paroxetine was superior to pause-squeeze technique in terms of efficacy.", "To investigate the interventional effect of comprehensive behaviour psychotherapy on the ejaculatory latency of premature ejaculation (PE) patients, sexual satisfaction of sexual partners, as well as its influence on the results of clinical treatment.\n Ninety PE patients were randomly divided into a psychological intervention group (n = 45) and a control group (n = 45). Both groups were given medicine therapy, and the former also received comprehensive behaviour psychotherapy for 6 weeks. All the patients were assessed with the Chinese index of sexual function for PE and ejaculatory latency in the vagina, and the clinical efficacy was compared between the two groups.\n Before treatment, the ejaculatory latency in the vagina was (0.69 +/- 0.25) min and (0.71 +/- 0.19) min respectively in the intervention and the control groups, as compared with (5.87 +/- 0.59) min and (4.76 +/- 0.54) min before treatment, with significant difference (P < 0.01). In the intervention group, the scores in the control of ejaculatory reflex, the sexual satisfaction of the patients and their sexual partners and anxiety or depress in sexual activity in CIPE were higher than in the control group, with significant difference between the two groups (t = 2.12, 2.31, 2.01, 2.24, P < 0.05). The difference in the SAS score after therapy was of significance (P < 0.01). A month after treatment, the effectivity rates of the two groups were 82.9% and 30% respectively, and the difference was significant (P < .01).\n Comprehensive behaviour psychotherapy obviously adds to the clinical efficacy of drugs in the treatment of PE." ]

[ "18518909", "8202032", "3460683", "9641743", "3859744", "10407809", "4312896", "19672975", "17994124", "1653063", "9373275", "9345068", "1746052", "7796018", "17046466", "2029465", "11345205", "7949165", "6576846", "3481038" ]

[ "Iron overload in survivors of childhood leukemia after allogeneic hematopoietic stem cell transplantation.", "Liver function studies in children with acute lymphocytic leukemia after cessation of therapy.", "Adverse prognostic influence of hepatitis B virus infection in acute lymphoblastic leukemia.", "Disease of the liver following bone marrow transplantation in children: incidence, clinical course and outcome in a long-term perspective.", "Acute and chronic hepatitis in childhood leukemia: a multicentric study from the Italian Pediatric Cooperative Group for Therapy of Acute Leukemia (AIL-AIEOP).", "[Chronic liver disease after treatment of malignancies in children].", "Irradiation of the liver in children: review of experience in the acute and chronic phases, and in the intact normal and partially resected.", "Veno-occlusive disease as a complication of preoperative chemotherapy for Wilms tumor: A clinico-pathological analysis.", "Abnormal liver enzymes two years after haematopoietic stem cell transplantation in children: prevalence and risk factors.", "Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission.", "Prevalence and natural history of hepatitis C infection in patients cured of childhood leukemia.", "Morbidity and mortality due to liver disease in children undergoing allogeneic bone marrow transplantation: a 10-year prospective study.", "Leukemia and liver disease in childhood: clinical and histological evaluation.", "Improved outcome for children with hepatoblastoma.", "Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia: a randomised trial.", "Delta virus and childhood leukemia.", "Long-term outcome of treatment with protocols AL841, AL851, and ALHR88 in children with acute lymphoblastic leukemia: results obtained by the Kyushu-Yamaguchi Children's Cancer Study Group.", "Hepatitis C virus infection in children treated for acute lymphoblastic leukemia.", "Chronic liver disease in children with leukemia in long-term remission.", "Transient acute hepatotoxicity of high-dose methotrexate therapy during childhood." ]

[ "Iron overload has not been studied extensively and prospectively in pediatric survivors of allogeneic hematopoietic stem cell transplantation (HSCT); therefore, we conducted a prospective long-term study of 133 survivors of childhood leukemia to assess the incidence of and risk factors for iron overload and to investigate its association with organ dysfunction. One yr after HSCT, the mean serum ferritin level was 1158 ng/mL (range, 22-3264 ng/mL), with 124 patients (93.2%) having a serum ferritin level that exceeded the upper limit of the normal range (110 ng/mL). Thereafter, the serum ferritin level declined over time. There was a positive correlation between the level of serum ferritin and that of total bilirubin (r = 0.21, p < 0.001) and glutamate pyruvate transaminase (r = 0.17, p < 0.001). A high concentration of serum ferritin was associated with low cardiac fractional shortening (r = -0.15, p = 0.047). In addition, patients with hypothyroidism and GH deficiency had a higher level of serum ferritin than those without (p < 0.02). We conclude that iron overload is common after HSCT and is associated with hepatic, cardiac, and endocrine dysfunction.", "We investigated liver function in 27 children with acute lymphocytic leukemia (ALL) after cessation of therapy. Induction therapy consisted of prednisolone+vincristine (VP regimen) alone (16 patients) or with addition of daunorubicin (4 patients) or L-asparaginase (7 patients). Patients treated with VP regimen received short courses of VP regimen every 12 weeks for the first year of maintenance. Twenty-five patients remained in first complete remission and had completed 3-year maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6-MP) 1-7 years prior to this study. Twenty-three patients had received transfusions of packed red blood cells or fresh whole blood (1-11 units; median: 2 units) but none had evidence of either hepatitis B or hepatitis C. Alanine aminotransferase (ALT), which was measured every 3 months during maintenance therapy, had values more than three times the upper limit of the normal range in 25% of the measurements in more than half of the patients. However, by 3 months after the completion of maintenance therapy, ALT had normalized in all patients and remained normal in all but two patients until the time of this study. Serum bilirubin, serum albumin, and prothrombin time were all within normal limits. Fasting and 2-hour postprandial total serum bile acids were high in 5 of 13 patients and in 6 of 13 patients, respectively. The ratio of cholic acids+deoxycholic acids to chenodeoxycholic acids+lithocholic acids was below 1 in all but two patients, whereas this ratio was above 1 in all controls. Our bile acid profile results indicate the necessity of careful long-term follow-up of survivors of ALL treated with hepatotoxic chemotherapy during childhood.", "Liver function test abnormalities were examined in a retrospective survey in a population of 90 children with acute lymphoblastic leukemia (ALL) treated in a similar fashion with therapy, using primarily methotrexate, mercaptopurine, vincristine, and prednisone. A twofold or greater elevation of serum glutamyl pyruvic transaminase (SGPT) was found in 80% of the patients during induction therapy, in 63% of the patients during maintenance therapy, and 31% of the patients who completed therapy. Circulating hepatitis B virus surface antigen (HBsAg) was noted in 26% of patients with liver function test abnormalities during maintenance therapy, and 45% of patients with liver function test abnormalities after the completion of therapy. Hepatitis B virus infection was therefore, the most important single cause of abnormal liver function during remission in our patient population. Though others have asserted that hepatitis B virus infection is relatively benign in immunosuppressed individuals, in our population, this agent often caused severe pathological and clinical sequelae. This may be related to the high frequency (50%) of co-infection with the delta agent in our HBsAg-positive patients. Furthermore, hepatitis B virus surface antigenemia conferred an adverse prognostic influence for these children in terms of their leukemia-free survival.", "Sixty-four consecutive cases of allogeneic (n = 16), autologous (n = 47) or syngeneic (n = 1) bone marrow transplantation (BMT) in children with haematological or lymphoid malignancy, aplasia or metabolic disease were reviewed to assess the incidence, clinical presentation and outcome of liver disease. Median follow-up time was 5 y (1.0-10). No liver diagnosis was established at the pre-transplant check-up. During the first 100 d post-transplant, 81% of the patients had impaired liver function as documented by various biochemical parameters. Three of 64 patients (5%) met diagnostic criteria for veno-occlusive disease. Four (25%) of the 16 receiving allografts were diagnosed as having acute graft vs host disease (GVHD) with liver involvement (grades II-III). No patient died of liver disease. During the late post-transplant follow-up, one patient developed HCV hepatitis after packed erythrocyte transfusion. Four patients were diagnosed as having chronic GVHD with liver involvement; three of them also had an episode of CMV hepatitis. At their latest follow-up, the patients with chronic GVHD had aminotransferase values 1.5-3 times the normal, whereas all other long-term survivors had normal or near-normal liver function tests. We conclude that the incidence of serious liver disease was low in this paediatric population of bone marrow recipients.", "The incidence of acute and chronic liver damage and its relation to hepatitis B virus (HBV) infection was evaluated in 164 consecutive children with acute leukemia seen in ten Italian hemato-pediatric units. Thirteen out of 164 children (7.9%) had acute hepatitis (AH) during treatment, while 8/90 (8.8%) showed an acute exacerbation of liver damage within 6 months after therapy withdrawal. Seven of the 13 children with AH while on therapy were HBsAg positive. In 12/13 cases, liver disease progressed to chronicity. Five of eight children who developed AH after completion of treatment were HBsAg positive. Eighty-nine patients (54.2%) developed biochemical evidence of chronic hepatitis during therapy; 48/89 were followed after cessation of treatment and 33 of them showed persisting evidence of liver cell necrosis. Thirty-three out of 133 children (24.8%) tested for serum HBsAg were found positive: 26 (78.7%) of them developed chronic hepatitis. Sixty-four out of 133 patients were evaluated after cessation of treatment: Chronic hepatitis persisted in 16/22 HBsAg-positive (72.7%) and in 17/42 HBsAg-negative (40.4%) children during follow-up. The outcome of these liver diseases after treatment withdrawal did not differ significantly in relation to HBV serology, suggesting that viral rather than toxic agents were responsible for liver damage also in most HBsAg-negative patients. The high incidence of chronic HBV infection in children with leukemia found in this multicentric study could suggest a need for active immunization with HBV vaccine, but the efficacy of such approach in this clinical setting is still to be validated.", "Chemotherapy, which has greatly improved the prognosis of children with malignant diseases, is potentially hepatotoxic. Furthermore, there is a risk for viral hepatitis acquired by blood products. In this study we looked for hepatotoxicity and for chronic viral hepatitis during and after chemotherapy in 50 unselected children with malignant diseases. 29 children had been treated for leukemia or lymphoma, 19 for solid tumors, 2 for histiocytosis. All patients had been treated before 1991 and had received blood products not screened for hepatitis C-antibodies. In 18 girls and 32 boys aged 12.3 years (range 6.7-24.5 years) hepatitis B- and hepatitis C-serology and liver function tests were measured during a routine check-up 3.6 years (range 0.5-11.8 years) after the last chemotherapy. Liver function tests during chemotherapy were reviewed retrospectively. During chemotherapy 86% of children showed increased ALT and AST levels, 10% had levels above 500 U/l. At follow up 16 children (32%) had pathological liver function tests, especially slightly increased AST and ALT, 13 of these 16 patients had chronic hepatitis C. In contrast only 2 of 34 patients with normal liver function tests had a viral hepatitis (p = 0.001). Patients with elevation of AST and ALT above 100 U/l during chemotherapy had significantly more often a viral hepatitis than those with normal or slightly elevated aminotransferases. Our study shows that hepatocellular damage is a frequent complication following chemotherapy. However this progresses to chronic liver disease very rarely unless the patient acquired a viral hepatitis. The prevalence of chronic hepatitis C was very high in our patients. As screening of blood products for hepatitis C-antibodies is routinely performed since 1991 this problem is likely to have decreased.", "nan", "Vincristine (VCR) and actinomycin D (ACD) form the backbone of chemotherapeutic regimens of Wilms tumor treatment. Veno-occlusive disease (VOD) is a potentially life-threatening complication of ACD.\n To investigate the incidence of VOD after preoperative chemotherapy and assess the effect of dose and frequency of administrating ACD on the occurrence of VOD.\n A single-center retrospective study of patients where liver biopsies were performed after 4 or 8 weeks of preoperative chemotherapy. Patients had localized or metastatic Wilms tumor and were treated according to SIOP 9, 93-1, or 2001 protocol. A correlation was analyzed between histologically confirmed VOD, laboratory parameters, and mode and frequency of ACD administration. Long-term hepatic toxicity was assessed 5 years after the end of therapy.\n Ninety-one patients were included in this analysis. Forty-one patients (45.1%) had histological evidence of VOD. The incidence of histologically proven VOD was significantly correlated with single administration of 45 microg/kg ACD (SIOP 2001 protocol) as compared to repeated dosing of l5 microg/kg (P = 0.003). Fifty-two percent of all patients had mild-to-severe abnormal liver enzymes 5 years after accomplishing therapy.\n Despite short-course preoperative chemotherapy regimen, patients are at risk of developing histological VOD. This risk is higher when ACD is administered in a 1-day 45 microg/kg regimen as compared to 3 days l5 microg/kg.", "To establish the prevalence of elevated liver enzymes in children transplanted in a Dutch haematopoietic stem cell transplantation (HSCT) centre, we retrospectively assessed AST and ALT values at 2 years after HSCT. Age, sex, diagnosis, type of transplant, conditioning regimen and early post-transplant complications involving the liver (veno-occlusive disease, acute GVHD, viral reactivation) were analysed as risk factors. AST and ALT values were available at 2 years after HSCT in 216 of 290 patients (75%) alive at that time and were above normal in 53 (25%) and at least twice normal in 17 (8%) patients. Older age at HSCT and a diagnosis of benign haematological disease are risk factors for abnormal liver enzymes late after HSCT. In half of the patients with benign haematological disease, iron overload is the most likely aetiological factor. Chronic hepatitis B or C is uncommon in our centre. In conclusion, the prevalence of abnormal liver enzymes late after HSCT in our centre is lower than reported in previous studies. Abnormal liver enzymes occur more often in children who are older at HSCT and transplanted for benign haematological disease. Long-term follow-up is crucial to establish if elevated liver enzymes precede clinical liver disease.", "Antibody to the recently identified hepatitis C virus (HCV) was investigated in sera of 50 leukemic children who had chronic liver disease (CLD), observed for 1 to 12.6 years after therapy withdrawal. All patients were tested for anti-HCV at regular intervals: Ortho-enzyme-linked immunosorbent assay (ELISA) test was performed in all cases. Reactive sera were also tested by recombinant immunoblotting assay to define the specificity of the results obtained by ELISA. Twelve cases (24%) were persistently positive (group A), 11 (22%) were transiently anti-HCV+ positive (group B), and 27 (54%) were negative. Mean SGPT peak during follow-up was significantly higher in group A (P = .014, A v B and P less than .00001, A v C). SGPT normalized off-therapy in 1 of 12 cases (group A), 10 of 11 (group B), and 19 of 27 (group C) (P = .0004, A v B and P = .012, A v C). Accordingly, liver histology, available in 37 patients, showed signs of chronic hepatitis in all patients in group A while most patients in group B and C had less severe liver lesions. These results indicate that HCV plays a significant role in the etiology of chronic hepatitis in leukemic patients and that persistent anti-HCV activity correlates with a more severe CLD, which could jeopardize the final prognosis of children cured of leukemia.", "The aim of this study was to ascertain prevalence and natural history of hepatitis C virus (HCV) infection in a large cohort of patients cured of childhood leukemia who had been followed prospectively for liver disease for at least 10 years since chemotherapy withdrawal: 114 consecutive patients entered the study. Liver function tests and ultrasonography were used to assess presence of liver disease. Patients were tested for antibody to HCV and for serum HCV-RNA at the end of chemotherapy and at the end of follow-up. At chemotherapy withdrawal, 56 patients (49%) were HCV-RNA positive, often without detectable anti-HCV, and in these cases, transaminase levels were more elevated during (P = .08) and after (P = .04) chemotherapy compared with HCV-RNA negative cases. Patients were then followed-up 13 to 27 years (mean, 17) after chemotherapy withdrawal. During this period, 38 initially anti-HCV negative patients seroconverted to anti-HCV and 17 initially anti-HCV positive cases lost reactivity. Forty patients were persistently HCV-RNA positive in serum, while 16 initially viremic patients became HCV-RNA negative during follow-up. At the end of the observation period, a persistent transaminase elevation was detected only in four HCV-RNA positive and anti-HCV positive cases, while no patient developed signs or symptoms of decompensated liver disease. Thus, hepatitis C was a frequent finding in long-term survivors after chemotherapy. It was associated with an atypical serologic profile and did not cause severe liver impairment over a period of 13 to 27 years.", "We have conducted a long-term prospective study of children undergoing bone marrow transplantation (BMT) to assess morbidity and mortality for liver disease. One hundred eleven consecutive children were enrolled between June 1985 and June 1995 and were followed-up for a median of 5.5 years after BMT. Before transplant 48/111 children (43%) had abnormal alanine aminotransferase (ALT), none were HBsAg+ and 4/111 were anti-HCV+. After BMT 4/111 patients (3. 6%) died of liver failure. No relationship was found between pretransplant hepatitis B (HBV) or C (HCV) infection or elevated transaminases and development of severe liver damage. Eighty-two out of one hundred and eleven patients (74%) had abnormalities of ALT after BMT, transient (n = 54) or persistent (n = 28). None developed clinical signs or symptoms of end stage liver disease or of cirrhosis during follow-up. No significant difference in prevalence of liver disease, was found between children with normal or abnormal ALT at BMT (relative risk [RR] = 1.04). HCV infection could be implicated in the etiology of chronic liver disease in 14/28 patients; 2 other patients were found infected by HBV alone (1 case) or combined with HCV (1 case). In the remaining 12 the etiology of chronic liver disease could not be defined. Posttransplant hepatitis B occurred in 4/111 children (3.6%), including a recipient from a donor who had been previously vaccinated against HBV, while no patient who had been vaccinated developed hepatitis B. The rate of posttransplant seroconversion to anti-HCV was 15%.", "Seventy-two consecutive patients with acute lymphocytic leukemia (ALL) who had undergone liver biopsy within 3 months of completing chemotherapy were studied to evaluate histological features after 2 to 3 years of chemotherapy and to correlate liver disease to the treatment schedule, the number of transfused blood units, and the identified etiology. Fibrosis due to antiblastic drugs was the most frequent histological finding. Histological liver disease was not related either to the chemotherapy schedule or the number of transfused blood units. HBV with or without delta virus and HCV infections were related to a more severe histological liver disease. In about 40% patients with chronic liver disease, no etiology was demonstrated. Immunohistochemistry revealed HBcAg in the liver of 3 HBsAg-negative patients. In conclusion, liver biopsy could be useful in patients with persistent abnormal liver function tests after the completion of chemotherapy and in patients with markers for hepatotropic virus infection.", "Between 1981 and 1993, 41 children were treated for hepatoblastoma. Clinical, radiological and pathological data were reviewed retrospectively, focusing on surgical aspects of treatment and outcome. Fourteen children underwent primary resection of the hepatic tumour. One infant with severe congenital anomalies received only palliative treatment. Of 26 with irresectable disease, pulsed cytotoxic chemotherapy (cisplatin and doxorubicin) enabled subsequent surgical excision in 22 and one child with persistent extensive intrahepatic disease was successfully treated by liver transplantation. Thus, with a policy of selective preoperative chemotherapy, 90 per cent of hepatoblastomas were resectable. There were no perioperative deaths from haemorrhage but one child died from an intraoperative tumour embolus. A total of 28 survivors, 27 of whom are disease-free, were followed for a median of 5 years. The cumulative probability of survival in patients treated with intent to cure was 67 per cent. Analysis of survival data suggested a favourable outcome for those with a pure fetal histological tumour subtype. These results demonstrate significant progress in the treatment of hepatoblastoma.", "6-mercaptopurine has been a standard component of long-term continuing treatment for childhood lymphoblastic leukaemia, whereas 6-thioguanine has been mainly used for intensification courses. Since preliminary data have shown that 6-thioguanine is more effective than 6-mercaptopurine, we compared the efficacy and toxicity of the two drugs for childhood lymphoblastic leukaemia.\n Consecutive children with lymphoblastic leukaemia diagnosed in the UK and Ireland between April, 1997, and June, 2002, were randomly assigned either 6-thioguanine (750 patients) or 6-mercaptopurine (748 patients) during interim maintenance and continuing therapy. All patients received 6-thioguanine during intensification courses. We analysed event-free and overall survival on an intention-to-treat basis. We obtained toxicity data using an adverse-event reporting system, with follow-up questionnaires to seek detailed information for specific toxicities. This trial is registered with the International Standard Randomised Controlled Number 26727615 with the name ALL97.\n After a median follow up of 6 years, there was no difference in event-free or overall survival between the two treatment groups. Although 6-thioguanine conferred a significantly lower risk of isolated CNS relapse than did 6-mercaptopurine (odds ratio [OR] 0.53, 95% CI 0.30-0.92, p=0.02), the benefit was offset by an increased risk of death in remission (2.22, 1.20-4.14, p=0.01), mainly due to infections during continuing therapy. Additionally, 95 patients developed veno-occlusive disease of the liver. Of these, 82 were randomly assigned 6-thioguanine, representing 11% of all 6-thioguanine recipients. On long-term follow-up, about 5% of 6-thioguanine recipients have evidence of non-cirrhotic portal hypertension due to periportal liver fibrosis or nodular regenerative hyperplasia.\n Compared with 6-mercaptopurine, 6-thioguanine causes excess toxicity without an overall benefit. 6-mercaptopurine should remain the thiopurine of choice for continuing therapy of childhood lymphoblastic leukaemia.", "We studied 145 children with acute lymphocytic leukemia (ALL) in remission who had been off chemotherapy for at least 2 years, to assess the prevalence of hepatitis delta virus (HDV) infection, and to determine whether HDV infection was associated with more severe chronic liver disease. The prevalence of chronic HBV infection was 41.5% (60/145). The prevalence of HDV infection among these patients with chronic HBV infection was 50% (30/60). Eighty-five patients were HBsAg-negative. There was evidence that HDV-infected children had more severe chronic liver disease than did HBsAg-positive, anti-HDV-negative patients: (1) their serum ALT levels were significantly more likely to be elevated at long-term follow-up (27/30 vs. 10/26, p = 0.0001); (2) their mean ALT levels were significantly higher 3 years after the cessation of chemotherapy (128 vs. 84 IU/L, p = 0.001); and (3) they were more likely to have either chronic acute hepatitis or cirrhosis when liver biopsy was done (18/23 vs. 6/18, p = 0.0038). Children who were HBsAg-negative had the lowest alanine aminotransferase (ALT) levels and were least likely to have chronic active hepatitis or cirrhosis (3/31). We conclude that infection with HDV in children with ALL is associated with serious chronic liver disease. In long-term survivors, HDV infection is a major cause of morbidity and an adverse prognostic factor in terms of leukemia-free survival.", "We analyzed the long-term outcome and late effects of treatment in 187 patients with childhood acute lymphoblastic leukemia (ALL) diagnosed between 1984 and 1990. Overall survival and event-free survival rates were 68.2% +/- 3.7% and 63.2% +/- 3.6% at 15 years, respectively. Of 55 patients who relapsed after achieving the first complete remission (CR), only 17.4% were rescued by salvage therapy. The advantage of stem cell transplantation over chemotherapy was observed only in those patients with bone marrow relapse during therapy. The SD for score height in patients maintaining the first CR significantly decreased at the time of final follow-up compared with that at diagnosis: 0.059 to -0.800 (P < .0001). The decrease was remarkable in patients younger than 5 years at diagnosis. Other late effects included mild liver dysfunction in 18% and hepatitis C virus infection in 9%. Congestive heart failure was observed in only 2.9% of patients despite the high cumulative dose of daunorubicin (450 mg/m2). Although the survival rates of patients on our protocols were comparable to those of other study groups, some modification, including reduction in dose of cranial irradiation and/or anticancer drugs, should be considered to reduce late adverse effects in survivors of childhood ALL.", "We studied 102 consecutive subjects after their completion of acute lymphoblastic leukemia (ALL)-directed chemotherapy, for evidence of hepatitis C virus (HCV) infection by enzyme immunoassay 2 and 3, second generation recombinant immunoblot assay and reverse transcription-polymerase chain reaction (PCR) for detection of circulating HCV-RNA. Forty-four patients (43%) had evidence of exposure to HCV; 30 of these were anti-HCV+. Of the 23 patients who were positive for both anti-HCV and HCV-RNA, 16 (69%) had a moderate increase in serum alanine aminotransferase (ALT) activity without clinical signs of liver disease. Fourteen patients were seronegative despite the presence of HCV-RNA in the serum. The proportion of different HCV genotypes was not significantly different from other anti-HCV+ patient groups. Although half of the patients with genotype III had normal ALT value, patients with normal ALT levels were represented in all genotype groups. Our study documents the prevalence of HCV infection in childhood ALL survivors, which is responsible for the majority of cases of non-B chronic liver disease in these patients. Whereas serologic screening identifies over 70% of patients with ongoing HCV infection, real HCV infection may be present even in the absence of a detectable humoral immune response to the virus. Based on this observation, determination of HCV-RNA by PCR should be recommended in patients in prolonged remission even if they test negative on serological assay. Normal ALT levels do not exclude the presence of HCV infection because the values were repeatedly normal in over half of our viremic patients.", "Liver disease during chemotherapy and after its completion was studied in 103 leukemic children in long-term remission. Seventy developed chronic liver disease during therapy; 22 out of 56 with adequate follow-up showed persisting abnormality or deterioration of liver function after stopping therapy. In 38 studied prospectively, biopsies were obtained at treatment withdrawal. Five showed chronic lobular, 17 chronic persistent, 9 chronic active hepatitis whereas 7 had minimal changes. These children had transiently detectable serum hepatitis-B virus (HBV) markers during (44.4%), at completion of (7.8%) and subsequent to (48.3%) chemotherapy. Serum HBV markers correlated significantly with both severity of histologic changes (P less than 0.05) and persistent biochemical abnormalities for over 6 months after treatment suspension (P less than 0.001). No direct relationship was found between drug administration and liver damage. The data from the study suggest that in leukemic children viral infections contribute to chronic liver damage, which can jeopardize the long-term prognosis of acute leukemia.", "Serial liver-enzyme determinations were performed on 36 children with acute lymphoblastic leukemia who were randomized to receive either conventional intrathecal methotrexate (MTX) therapy with cranial irradiation, or an investigational high-dose MTX regimen consisting of 10 courses of 33,600 mg/m2 over 24 hours, with high-dose leucovorin rescue. Both groups of patients received intermittent low-dose oral MTX during maintenance therapy. Serum transaminase elevations in the group of conventionally treated patients were infrequent and moderate in severity (less than 300 IU/liter). In the investigational group, however, the majority of patients had severe, acute increases in SGPT (greater than 300 IU/liter), with peaks up to 1000 to 2000 IU/liter. The incidence and severity of acute transaminasemia were directly proportional to the number of high-dose MTX courses received: courses 1, 2, 3, 4, 5, and 6 caused transaminase elevations in 31%, 50%, 50%, 73%, 100%, and 100% of courses, respectively, and 0%, 14%, 20%, 44%, 55%, and 92%, respectively, were over 300 IU/liter. Patients in both treatment groups developed a pattern of increasing serum alkaline phosphatase concentrations after initiation of low-dose oral MTX therapy; isoenzyme analysis indicated that this effect was osseous rather than hepatic. Serum bilirubin was rarely elevated. Transaminases returned to normal within 1 to 2 weeks after each high-dose MTX treatment, and with follow-up for as long as 7 years, no patient has developed clinical evidence of residual liver disease, after 3 years of high-dose MTX therapy and multiple other antileukemia drugs. The acute hypertransaminasemia frequently observed after high-dose MTX therapy is transient and reversible, and, in children, does not appear to result in chronic liver disease." ]

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[ "Integrating clinical nurse specialists into the treatment of primary care patients with depression.", "Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial.", "Randomized controlled trial to assess the effectiveness of a primary health care liaison worker in promoting shared care for opiate users.", "The North Dublin randomized controlled trial of structured diabetes shared care.", "Patient-held shared care records for individuals with mental illness. Randomised controlled evaluation.", "The effect on hospital admissions of psychiatric case management involving general practitioners: preliminary results.", "A randomized trial of relapse prevention of depression in primary care.", "Integrated care for diabetes: clinical, psychosocial, and economic evaluation. Diabetes Integrated Care Evaluation Team.", "Improving foot care for people with diabetes mellitus--a randomized controlled trial of an integrated care approach.", "The Pathways Study: a randomized trial of collaborative care in patients with diabetes and depression.", "Coordinating and standardizing long-term care: evaluation of the west of Scotland shared-care scheme for hypertension.", "Multifaceted shared care intervention for late life depression in residential care: randomised controlled trial.", "Randomized, controlled trial of integrated heart failure management: The Auckland Heart Failure Management Study.", "Stepped collaborative care for primary care patients with persistent symptoms of depression: a randomized trial.", "Exploratory cluster randomised controlled trial of shared care development for long-term mental illness.", "Sharing the care of diabetic patients between hospital and general practitioners: does it work?", "A chronic disease management programme can reduce days in hospital for patients with chronic obstructive pulmonary disease.", "A randomized controlled trial of shared care versus routine care for patients receiving oral anticoagulant therapy." ]

[ "To examine the effectiveness of integrating generalist and specialist care for veterans with depression.\n We conducted a randomized trial of patients screening positive for depression at two Veterans Affairs Medical Center general medicine clinic firms. Control firm physicians were notified prior to the encounter when eligible patients had PRIME-MD depression diagnoses. In the intervention firm, a mental health clinical nurse specialist (CNS) was to: design a treatment plan; implement that plan with the primary care physician; and monitor patients via telephone or visits at two weeks, one month and two months. Primary outcomes (depressive symptoms, patient satisfaction with health care) were collected at 3 and 12 months.\n Of 268 randomized patients, 246 (92%) and 222 (83%) completed 3- and 12-month follow-up interviews. There were no between-group differences in depressive symptoms or satisfaction at 3 or 12 months. The intervention group had greater chart documentation of depression at baseline (63% versus 33%, p = 0.003) and a higher referral rate to mental health services at 3 months (27% versus 9%, p = 0.019). There was no difference in the rate of new prescriptions for, or adequate dosing of, anti-depressant medications. In 40% of patients, CNSs disagreed with the PRIME-MD depression diagnosis, and their rates of watchful waiting were correspondingly high.\n Implementing an integrated care model did not occur as intended. Experienced CNSs often did not see the need for treatment in many primary care patients identified by the PRIME-MD. Integrating integrated care models in actual practice may prove challenging.", "Few depressed older adults receive effective treatment in primary care settings.\n To determine the effectiveness of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) collaborative care management program for late-life depression.\n Randomized controlled trial with recruitment from July 1999 to August 2001.\n Eighteen primary care clinics from 8 health care organizations in 5 states.\n A total of 1801 patients aged 60 years or older with major depression (17%), dysthymic disorder (30%), or both (53%).\n Patients were randomly assigned to the IMPACT intervention (n = 906) or to usual care (n = 895). Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education, care management, and support of antidepressant management by the patient's primary care physician or a brief psychotherapy for depression, Problem Solving Treatment in Primary Care.\n Assessments at baseline and at 3, 6, and 12 months for depression, depression treatments, satisfaction with care, functional impairment, and quality of life.\n At 12 months, 45% of intervention patients had a 50% or greater reduction in depressive symptoms from baseline compared with 19% of usual care participants (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.71-4.38; P<.001). Intervention patients also experienced greater rates of depression treatment (OR, 2.98; 95% CI, 2.34-3.79; P<.001), more satisfaction with depression care (OR, 3.38; 95% CI, 2.66-4.30; P<.001), lower depression severity (range, 0-4; between-group difference, -0.4; 95% CI, -0.46 to -0.33; P<.001), less functional impairment (range, 0-10; between-group difference, -0.91; 95% CI, -1.19 to -0.64; P<.001), and greater quality of life (range, 0-10; between-group difference, 0.56; 95% CI, 0.32-0.79; P<.001) than participants assigned to the usual care group.\n The IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practices.", "Recent national guidelines emphasize the requirement for all general practitioners to manage drug users within a shared care scheme and suggest that a primary health care liaison worker (PHCLW) may facilitate these arrangements. We undertook a group-randomized, randomized controlled trial to determine the effectiveness of a PHCLW in promoting shared care.\n Primary health care teams in Stockport Health Authority, North West England, were randomly allocated to either an intervention arm, who were offered the services of a PHCLW, or to a control arm, who were offered standard support from the community drug team (CDT). The proportion of CDT clients with a history of regular opiate misuse who were in shared care 12 months after randomization was compared across study arms.\n Eighteen (24.0 per cent) of the 75 CDT clients in the intervention arm but none of the 80 CDT clients in the control arm were in shared care at 12 months (chi2 = 9.37, df = 1, p < 0.01; 95 per cent confidence interval 8.6-39.4 per cent).\n A PHCLW can significantly increase the number of CDT clients in shared care arrangements.", "A new diabetes shared care service was introduced in North Dublin. It was designed as a randomized controlled trial with a complex intervention comprising education of participating practitioners, the introduction of a community-based diabetes nurse specialist, local agreement on clinical protocols and structured communication across the primary-secondary care interface.\n Our aim was to assess the feasibility and effectiveness of a structured diabetes shared care service in a mixed health care system and to analyse the impact on total patient care.\n A Cluster randomized controlled trial lasting 18 months was carried out in 183 patients with type 2 diabetes from 30 general practices in North Dublin. Biophysical outcomes (HbA1c, blood pressure, body mass index), psychosocial measures (smoking status and Diabetes Clinic Treatment Satisfaction and Diabetes Well-being scores) and process outcomes were collected.\n There were significant improvements in diabetes care delivery and in psychosocial outcomes, but no significant improvements in biomedical outcomes. Process data collection revealed a significant increase in diabetes care-related activity for participating patients with an increase in structured annual reviews and fewer patients defaulting from care. There were also significant improvements in information exchange between primary and secondary care.\n Structured diabetes shared care, in a mixed health care system, can produce significant improvements in diabetes care delivery and in psychosocial outcomes for patients, with improved information exchange across the primary-secondary care interface.", "Few formalized shared care schemes exist within psychiatry and the evidence base for sharing psychiatric care is weak.\n To evaluate the utility of patient-held shared care records for individuals with long-term mental illness.\n Cluster-randomised controlled parallel-group 12-month trial involving 90 patients with long-term mental illness drawn from 28 general practices.\n Carrying a shared care record had no significant effect on mental state or satisfaction with psychiatric services. Compared with controls, patients in the shared care group were no more likely to be admitted (relative risk 1.2, 95% CI 0.86-1.67) and attend clinic (relative risk 0.96, 95% CI 0.67-1.36) over the study period. Uptake of the shared care scheme was low by patients and professionals alike. Subjects with psychotic illness were significantly less likely to use their records (relative risk 0.51, 95% CI 0.27-0.99).\n Patient-held records may not be helpful for patients with long-term mental illness.", "A two year follow-up of two matched groups of subjects with chronic severe mental illness was performed in order to evaluate a new psychiatric case management system. One group (n = 59) received care through psychiatric case management, using an assertive community treatment model that directly involved general practitioners. The other group, matched for age, sex, diagnostic group and number of hospital admissions, received standard outpatient care. Comparing the two years before and after case management, the experimental group showed a dramatic fall in inpatient admission days while the control group admission days remained the same (median difference in admission days across matched subject pairs = 64.5, 95% C.I. from 134.5 to 16). The experimental group remained out of hospital longer before first readmission (Kaplan-Meier survival analysis, P = 0.002). This type of case management programme can shorten or prevent admissions to psychiatric hospitals of patients with chronic mental illness, and increase their time before readmission.", "Despite high rates of relapse and recurrence, few primary care patients with recurrent or chronic depression are receiving continuation and maintenance-phase treatment. We hypothesized that a relapse prevention intervention would improve adherence to antidepressant medication and improve depression outcomes in high-risk patients compared with usual primary care.\n Three hundred eighty-six patients with recurrent major depression or dysthymia who had largely recovered after 8 weeks of antidepressant treatment by their primary care physicians were randomized to a relapse prevention program (n = 194) or usual primary care (n = 192). Patients in the intervention group received 2 primary care visits with a depression specialist and 3 telephone visits over a 1-year period aimed at enhancing adherence to antidepressant medication, recognition of prodromal symptoms, monitoring of symptoms, and development of a written relapse prevention plan. Follow-up assessments were completed at 3, 6, 9, and 12 months by a telephone survey team blinded to randomization status.\n Those in the intervention group had significantly greater adherence to adequate dosage of antidepressant medication for 90 days or more within the first and second 6-month periods and were significantly more likely to refill medication prescriptions during the 12-month follow-up compared with usual care controls. Intervention patients had significantly fewer depressive symptoms, but not fewer episodes of relapse/recurrence over the 12-month follow-up period.\n A relapse prevention program targeted to primary care patients with a high risk of relapse/recurrence who had largely recovered after antidepressant treatment significantly improved antidepressant adherence and depressive symptom outcomes.", "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 evaluate a model of integrated diabetic footcare, for identification and clinical management of the high risk diabetic foot, centred on the primary care-based diabetic annual review.\n A pragmatic randomized controlled study was undertaken with matched cluster randomization of practices from 10 towns drawn from mid and east Devon responsible for the care of 1,939 people with diabetes (age > or =18 years). Outcome measures were patients' attitudes regarding the value and importance of footcare, patients' footcare knowledge, healthcare professionals' footcare knowledge and pattern of service utilization.\n Attitudes towards footcare improved in both intervention and control groups (mean percentage change 3.91, 0.68) with a significant difference in change of 3.18 (95% confidence interval (CI) 1.29-5.07) between the groups. Patients' knowledge about diabetic foot problems improved significantly in both groups (mean percentage change 1.09, 1.32) but with no significant difference in change: -0.09 (95% CI -1.81-1.63) between groups. Health professionals' knowledge scores improved in the intervention group (mean percentage change 13.2; P < 0.001). No improvement was seen in the control group (mean percentage change -0.2; P = 0.1) with a significant difference in change of 13.46 (95% CI 8.30-18.62) between groups. Appropriate referrals from intervention practices to the specialized foot clinic rose significantly (P = 0.05) compared with control practices (P = 0.14).\n Provision of integrated care arrangements for the diabetic foot has a positive impact on primary care staffs' knowledge and patients' attitudes resulting in an increased number of appropriate referrals to acute specialist services.", "There is a high prevalence of depression in patients with diabetes mellitus. Depression has been shown to be associated with poor self-management (adherence to diet, exercise, checking blood glucose levels) and high hemoglobin A1c (HbA1c) levels in patients with diabetes.\n To determine whether enhancing quality of care for depression improves both depression and diabetes outcomes in patients with depression and diabetes.\n Randomized controlled trial with recruitment from March 1, 2001, to May 31, 2002.\n Nine primary care clinics from a large health maintenance organization.\n A total of 329 patients with diabetes mellitus and comorbid major depression and/or dysthymia. Intervention Patients were randomly assigned to the Pathways case management intervention (n = 164) or usual care (n = 165). The intervention provided enhanced education and support of antidepressant medication treatment prescribed by the primary care physician or problem-solving therapy delivered in primary care.\n Independent blinded assessments at baseline and 3, 6, and 12 months of depression (Hopkins Symptom Checklist 90), global improvement, and satisfaction with care. Automated clinical data were used to evaluate adherence to antidepressant regimens, percentage receiving specialty mental health visits, and HbA1c levels.\n When compared with usual care patients, intervention patients showed greater improvement in adequacy of dosage of antidepressant medication treatment in the first 6-month period (odds ratio [OR], 4.15; 95% confidence interval [CI], 2.28-7.55) and the second 6-month period (OR, 2.90; 95% CI, 1.69-4.98), less depression severity over time (z = 2.84, P = .004), a higher rating of patient-rated global improvement at 6 months (intervention 69.4% vs usual care 39.3%; OR, 3.50; 95% CI, 2.16-5.68) and 12 months (intervention 71.9% vs usual care 42.3%; OR, 3.50; 95% CI, 2.14-5.72), and higher satisfaction with care at 6 months (OR, 2.01; 95% CI, 1.18-3.43) and 12 months (OR, 2.88; 95% CI, 1.67-4.97). Although depressive outcomes were improved, no differences in HbA1c outcomes were observed.\n The Pathways collaborative care model improved depression care and outcomes in patients with comorbid major depression and/or dysthymia and diabetes mellitus, but improved depression care alone did not result in improved glycemic control.", "The long-term management of patients with chronic conditions such as hypertension presents problems for the health services. Shared care addresses these by coordinating care and defining responsibilities.\n This study set out to investigate the feasibility, acceptability and cost effectiveness of shared general practitioner-hospital care for well-controlled hypertensive patients in an urban area by comparing three matched groups of patients.\n A total of 554 outpatient clinic attenders, considered suitable for shared care by their consultant, were randomly allocated to shared care or follow up in the outpatient clinic; a third group of 277 patients was selected from a nurse practitioner clinic. Main outcome measures were the proportion of patients in the second year of follow up who had undergone a complete review (blood pressure measurement, serum creatinine level result and electrocardiograph report), acceptability to patients and general practitioners as assessed by questionnaire, and cost per complete review in year two (National Health Service and patient costs).\n After two years 220 (82%) shared care patients had had a complete review compared with 146 (54%) outpatient clinic attenders and 202 (75%) nurse practitioner clinic attenders. Blood pressure control was similar in each group. Of 297 general practitioners invited, 85% wished to participate in the study; 61% of questionnaire respondents subsequently wanted shared care to continue while 25% were unsure. Half of the patients receiving shared care preferred this method of follow up. The rank order of cost-effectiveness ratios was shared care, nurse practitioner care and conventional outpatient care, relative differences being most marked when only patient costs were considered.\n Shared care for hypertension is feasible in an urban setting, acceptable to the majority of participants and is a cost-effective method of long-term follow up.", "To evaluate the effectiveness of a population based, multifaceted shared care intervention for late life depression in residential care.\n Randomised controlled trial, with control and intervention groups studied one after the other and blind follow up after 9.5 months.\n Population of residential facility in Sydney living in self care units and hostels.\n 220 depressed residents aged >/=65 without severe cognitive impairment.\n The shared care intervention included: (a) multidisciplinary consultation and collaboration, (b) training of general practitioners and carers in detection and management of depression, and (c) depression related health education and activity programmes for residents. The control group received routine care.\n Geriatric depression scale.\n Intention to treat analysis was used. There was significantly more movement to \"less depressed\" levels of depression at follow up in the intervention than control group (Mantel-Haenszel stratification test, P=0.0125). Multiple linear regression analysis found a significant intervention effect after controlling for possible confounders, with the intervention group showing an average improvement of 1.87 points on the geriatric depression scale compared with the control group (95% confidence interval 0.76 to 2.97, P=0.0011).\n The outcome of depression among elderly people in residential care can be improved by multidisciplinary collaboration, by enhancing the clinical skills of general practitioners and care staff, and by providing depression related health education and activity programmes for residents.", "To determine the effect of an integrated heart failure management programme, involving patient and family, primary and secondary care, on quality of life and death or hospital readmissions in patients with chronic heart failure.\n This trial was a cluster randomized, controlled trial of integrated primary/secondary care compared with usual care for patients with heart failure. The intervention involved clinical review at a hospital-based heart failure clinic early after discharge, individual and group education sessions, a personal diary to record medication and body weight, information booklets and regular clinical follow-up alternating between the general practitioner and heart failure clinic. Follow-up was for 12 months. One hundred and ninety-seven patients admitted to Auckland Hospital with an episode of heart failure were enrolled in the study. There was no significant difference between the intervention and control groups for the combined end-point of death or hospital readmission. The physical dimension of quality of life showed a greater improvement in the intervention group from baseline to 12 months compared with the control group (-11.1 vs -5.8 respectively, 2 P=0.015). The main effect of the intervention was attributable to the prevention of multiple admissions (56 intervention group vs 95 control group, 2 P=0.015) and associated reduction in bed days.\n This integrated management programme for patients with chronic heart failure improved quality of life and reduced total hospital admissions and total bed days.\n Copyright 2001 The European Society of Cardiology.", "Despite improvements in the accuracy of diagnosing depression and use of medications with fewer side effects, many patients treated with antidepressant medications by primary care physicians have persistent symptoms.\n A group of 228 patients recognized as depressed by their primary care physicians and given antidepressant medication who had either 4 or more persistent major depressive symptoms or a score of 1.5 or more on the Hopkins Symptom Checklist depression items at 6 to 8 weeks were randomized to a collaborative care intervention (n = 114) or usual care (n = 114) by the primary care physician. Patients in the intervention group received enhanced education and increased frequency of visits by a psychiatrist working with the primary care physician to improve pharmacologic treatment. Follow-up assessments were completed at 1, 3, and 6 months by a telephone survey team blinded to randomization status.\n Those in the intervention group had significantly greater adherence to adequate dosage of medication for 90 days or more and were more likely to rate the quality of care they received for depression as good to excellent compared with usual care controls. Intervention patients showed a significantly greater decrease compared with usual care controls in severity of depressive symptoms over time and were more likely to have fully recovered at 3 and 6 months.\n A multifaceted program targeted to patients whose depressive symptoms persisted 6 to 8 weeks after initiation of antidepressant medication by their primary care physician was found to significantly improve adherence to antidepressants, satisfaction with care, and depressive outcomes compared with usual care.", "Primary care clinicians have a considerable amount of contact with patients suffering from long-term mental illness. The United Kingdom's National Health Service now requires general practices to contribute more systematically to care for this group of patients.\n To determine the effects of Mental Health Link, a facilitation-based quality improvement programme designed to improve communication between the teams and systems of care within general practice. Design of study: Exploratory cluster randomised controlled trial.\n Twenty-three urban general practices and associated community mental health teams.\n Practices were randomised to service development as usual or to the Mental Health Link programme. Questionnaires and an audit of notes assessed 335 patients' satisfaction, unmet need, mental health status, processes of mental and physical care, and general practitioners' satisfaction with services and beliefs about service development. Service use and intervention costs were also measured.\n There were no significant differences in patients' perception of their unmet need, satisfaction or general health. Intervention patients had fewer psychiatric relapses than control patients (mean = 0.39 versus 0.71, respectively, P = 0.02) but there were no differences in documented processes of care. Intervention practitioners were more satisfied and services improved significantly for intervention practices. There was an additional mean direct cost of pound 63 per patient with long-term mental illness for the intervention compared with the control.\n Significant differences were seen in relapse rates and practitioner satisfaction. Improvements in service development did not translate into documented improvements in care. This could be explained by the intervention working via the improvements in informal shared care developed through better link working. This type of facilitated intervention tailored to context has the potential to improve care and interface working.", "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 steady increase in chronic obstructive pulmonary disease (COPD) admissions was addressed by enhancing primary care to provide intensive chronic disease management.\n To compare the effect of a disease management programme, including a COPD management guideline, a patient-specific care plan and collaboration between patients, general practitioners, practice nurses, hospital physicians and nurse specialists with conventional care, on hospital admissions and quality of life.\n One hundred and thirty-five patients with a clinical diagnosis of moderate to severe COPD were identified from hospital admission data and general practice records. General practices were randomized to either conventional care (CON), or the intervention (INT). Pre- and post-study assessment included spirometry, Shuttle Walk Test, Short Form-36, and the Chronic Respiratory Questionnaire (CRQ). Admission data were compared for 12 months prior to and during the trial.\n For respiratory conditions, mean hospital bed days per patient per year for the INT group were reduced from 2.8 to 1.1, whereas those for the CON group increased from 3.5 to 4.0 (group difference, P = 0.030) The INT group also showed an improvement for two dimensions of the CRQ, fatigue (P = 0.010) and mastery (P = 0.007).\n A chronic disease management programme for COPD patients that incorporated a variety of interventions, including pulmonary rehabilitation and implemented by primary care, reduced admissions and hospital bed days. Key elements were patient participation and information sharing among healthcare providers.", "To evaluate the effect of a shared care programme (SCP), defined as a scheme based on shared responsibility, enhanced information exchange, continues medical education and explicit clinical guidelines, between general practitioners (GPs) and a hospital outpatient clinic (HOC), on oral anticoagulant therapy (OAT).\n The study was a 2-year prospective, randomized, controlled trial, preceded by a 1-year period of observation.\n The HOC, GPs, and OAT patients in the admission area of Aarhus University Hospital, Aarhus County, Denmark, covering 310 300 inhabitants.\n A total of 207 GPs, including their enlisted patients on OAT, were invited, and 61.4% accepted participation. They were randomized into an intervention group [group-INT: 64 GPs and 453 patients (170 patients on OAT throughout the study period, i.e. full follow-up)], and a control group [group-CON: 63 GPs and 422 patients (173 with full follow-up)]. The remaining 80 GPs served as a nonresponder group (group-NON) of 485 patients (184 with full follow-up).\n Therapeutic control of OAT in terms of time spent by the patients within the therapeutic interval (TI) of an international normalized ratio (INR) between 2.0 and 3.5.\n The groups did not differ significantly with regard to age, sex, OAT indication, anticoagulant drug used, or the therapeutic control at baseline. In a comparison based on intention-to-treat principles, the therapeutic control increased statistical significance amongst patients with full follow-up in group-INT compared with group-CON (median time within TI: group INT = 86.6% vs. 80.5%, P = 0.007).\n An SCP of anticoagulant management is effective in reducing patient time outside the therapeutic INR interval in OAT patients randomly assigned to an SCP, as compared with a control group." ]

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[ "GnRH antagonist in IVF poor-responder patients: results of a randomized trial.", "Comparing GnRH agonist long protocol and GnRH antagonist protocol in outcome the first cycle of ART.", "A modified gonadotropin-releasing hormone (GnRH) antagonist protocol failed to increase clinical pregnancy rates in comparison with the long GnRH protocol.", "A randomized comparison of two ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) antagonist cotreatment for in vitro fertilization commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the standard long GnRH agonist protocol.", "Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT).", "Comparison of GnRH antagonist with long GnRH agonist protocol after OCP pretreatment in PCOs patients.", "A randomized prospective trial comparing gonadotropin-releasing hormone (GnRH) antagonist/recombinant follicle-stimulating hormone (rFSH) versus GnRH-agonist/rFSH in women pretreated with oral contraceptives before in vitro fertilization.", "Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial.", "Comparison of outcome of clomiphene citrate/human menopausal gonadotropin/cetrorelix protocol and buserelin long protocol--a randomized study.", "Comparison of multiple dose GnRH antagonist and minidose long agonist protocols in poor responders undergoing in vitro fertilization: a randomized controlled trial.", "Use of a GnRH antagonist in controlled ovarian hyperstimulation for assisted conception in women with polycystic ovary disease: a randomized, prospective, pilot study.", "Comparisons of different dosages of gonadotropin-releasing hormone (GnRH) antagonist, short-acting form and single, half-dose, long-acting form of GnRH agonist during controlled ovarian hyperstimulation and in vitro fertilization.", "Follicular growth and oocyte maturation in GnRH agonist and antagonist protocols for in vitro fertilisation and embryo transfer.", "Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation.", "IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study.", "Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction.", "Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study.", "Cetrorelix protocol versus gonadotropin-releasing hormone analog suppression long protocol for superovulation in intracytoplasmic sperm injection patients older than 40.", "A randomised study of GnRH antagonist (cetrorelix) versus agonist (busereline) for controlled ovarian stimulation: effect on safety and efficacy.", "GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial.", "Effect of antagonists vs agonists on in vitro fertilization outcome.", "Prospective, randomized, comparative study of leuprorelin + human menopausal gonadotropins versus ganirelix + recombinant follicle-stimulating hormone in oocyte donors and pregnancy rates among the corresponding recipients.", "Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. European Cetrorelix Study Group.", "A mild treatment strategy for in-vitro fertilisation: a randomised non-inferiority trial.", "The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study.", "Initiation of GnRH antagonist on Day 1 of stimulation as compared to the long agonist protocol in PCOS patients. A randomized controlled trial: effect on hormonal levels and follicular development.", "Comparison of embryological and clinical outcome in GnRH antagonist vs. GnRH agonist protocols for in vitro fertilization in PCOS non-obese patients. A prospective randomized study.", "A comparative randomized trial to assess the impact of oral contraceptive pretreatment on follicular growth and hormone profiles in GnRH antagonist-treated patients.", "Comparison of GnRH agonists and antagonists in normoresponder IVF/ICSI in Turkish female patients.", "Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a randomized study.", "Follicular fluid anti-Müllerian hormone and inhibin B concentrations: comparison between gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist cycles.", "Comparison of GnRH antagonist protocol with or without oral contraceptive pill pretreatment and GnRH agonist low-dose long protocol in low responders undergoing IVF/intracytoplasmic sperm injection.", "Comparison of mild stimulation and conventional stimulation in ART outcome.", "Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin)." ]

[ "The aim of this prospective study was to evaluate the efficacy of gonadotrophin-releasing hormone antagonist (GnRH) in comparison with the standard long protocol in poor-responder patients. Sixty patients with poor ovarian response in previous treatment cycles were randomized into two groups: group A (n = 30) was stimulated with a standard long protocol, and group B (n = 30) received GnRH antagonist. Vaginal ultrasound was performed to evaluate ovarian response. There was a significantly reduced duration of ovarian stimulation (9.8 +/- 0.8 versus 14.6 +/- 1.2, P = 0.001) in group B in comparison with group A, and a reduced number of ampoules was used in group B (49.3 +/- 4.3 versus 72.6 +/- 6.8, P = 0.0001). In group B, the number of oocytes retrieved was significantly higher than in group A (5.6 +/- 1.6 versus 4.3 +/- 2.2, P = 0.02) and there was an increased number of follicles with a diameter >15 mm at human chorionic gonadotrophin administration in group B (P = 0.0001). Fewer cycles were cancelled with the use of an antagonist protocol. Five pregnancies (17% for embryo transfer) were obtained with GnRH antagonist protocol and two (7% for embryo transfer) with GnRH agonist protocol.", "This prospective study evaluated the efficacy of gonadotropin-releasing hormone (GnRH) antagonist protocol in comparison with the GnRH agonist protocol in the first cycle of assisted reproductive technique (ART).\n We randomized 235 patients undergoing ART for the first time. The first group was stimulated with a standard long protocol and the second group stimulated with GnRH antagonis.\n There was no statistically significant difference in the age, infertility cause, basal FSH, BMI, the number of oocytes retrieved, number of M2 oocytes, embryo obtained and endometrial thickness between the two groups. But Serum estradiol, consumption of gonadotropins and ovarian hyperstimulation syndrome were significantly lower in the antagonist protocol. Cancellation rate of embryo transfer due to poor-quality embryo in the antagonist protocol was higher, but it was not significant. There was no significant difference in the clinical pregnancy and ongoing pregnancy between the two groups.\n GnRH-antagonist is an effective, safe, and well-tolerated alternative to agonist in the first cycle of ART.", "The purpose of this prospective randomized study was to compare stimulation characteristics and IVF outcomes of the standard long GnRH agonist protocol for ovarian stimulation with a modified GnRH antagonist protocol. Starting GnRH antagonist in a flexible protocol according to the size of the leading follicle, with simultaneous augmentation of 75 IU recombinant FSH, failed to increase clinical pregnancy rates.", "Extending the FSH window for multifollicular development by administering FSH from the midfollicular phase onward constitutes a novel mild protocol for ovarian stimulation for in vitro fertilization (IVF) based on the physiology of single dominant follicle selection in normo-ovulatory women. We compared outcomes from this protocol with two other stimulation protocols. One hundred and forty-two normo-ovulatory patients with an indication for IVF (or IVF/ICSI) were randomized to a GnRH agonist long protocol (group A; n = 45) or one of two GnRH antagonist protocols commencing recombinant FSH on cycle d 2 (group B; n = 48) or cycle d 5 (group C; n = 49). A fixed dose (150 IU/d) of rFSH was used for ovarian stimulation, and GnRH antagonist cotreatment was initiated on the day when the leading follicle reached 14 mm diameter. Group C showed a shorter duration of stimulation (median duration, 11, 9, and 8 d for groups A, B, and C, respectively; P < 0.001), reflected in a significantly lower total dose of rFSH used (median amount of rFSH, 1650, 1350, and 1200 IU for groups A, B, and C, respectively; P < 0.001). In group C more cycles were cancelled during the stimulation phase due to insufficient response, resulting in a lower percentage of oocyte retrievals (84%, 73%, and 63% for groups A, B, and C; P = 0.02). However, women in group C obtained better quality embryos (percentage of embryo score of 1 for best embryo, 29%, 37%, and 61% for groups A, B, and C, respectively; P = 0.008), resulting in more transfers per oocyte retrieval (68%, 71%, and 90% for groups A, B, and C, respectively; P = 0.04). After profound ovarian stimulation (groups A and B) only 7% of the patients who retrieved four oocytes or less conceived, whereas after mild stimulation (group C) 67% of these patients conceived (P < 0.01). Overall, no differences were found among the three groups comparing pregnancy rate per started IVF cycle. In conclusion, application of the described mild ovarian stimulation protocol resulted in pregnancy rates per started IVF cycle similar to those observed after profound stimulation with GnRH agonist cotreatment despite shorter stimulation and a 27% reduction in exogenous FSH. A higher cancellation rate before oocyte retrieval was compensated by improved embryo quality concomitant with a higher chance of undergoing embryo transfer. A relatively low number of oocytes retrieved after mild ovarian stimulation distinctly differs from the pathological reduction in the number of oocytes retrieved after profound ovarian stimulation (poor response) associated with poor IVF outcome. The relatively small number of oocytes obtained after mild ovarian stimulation may represent the best of the cohort in a given cycle.", "Women with polycystic ovary syndrome (PCOS) are at risk of developing ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. Use of GnRH antagonist in the general subfertile population is associated with lower incidence of OHSS than agonists and similar probability of live birth but it is unclear if this is true for patients with PCOS. Our aim was to compare the flexible GnRH antagonist and GnRH agonist long protocols in patients with PCOS undergoing IVF (primary end-point: ongoing pregnancy rate per patient randomized).\n In this randomised controlled trial (RCT), 220 patients with PCOS were randomly allocated in two groups: long GnRH agonist down-regulation protocol (n = 110) and flexible GnRH antagonist protocol (n = 110).\n No differences were observed in ongoing pregnancy rates [50.9 versus 47.3%, difference 3.6%, 95% confidence interval (CI): -9.6 to +16.8%] in the agonist and antagonist protocols, respectively. Incidence of OHSS Grade II was lower in the antagonist compared with agonist group (40.0 versus 60.0%, difference -20.0%, 95% CI: -7.1 to -32.9%, P < 0.01). Duration of stimulation (10 versus 12 days, difference 2 days, 95% CI: +1 to +2, P < 0.001) and total gonadotrophin required (1575 versus 1850 IU, difference -275 IU, 95% CI: -25 to -400, P < 0.05) were also lower in the antagonist compared with agonist protocol.\n The current RCT suggests that the flexible GnRH antagonist protocol is associated with a similar ongoing pregnancy rate, lower incidence of OHSS grade II, lower gonadotrophin requirement and shorter duration of stimulation, compared with GnRH agonist. The GnRH antagonist might be the treatment choice for patients with PCOS undergoing IVF. The study was registered at clinicaltrials.gov. ID: NCT00417144.", "To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome (PCOs) patients undergoing their first ART cycle.\n Prospective randomized controlled trial. University-based tertiary fertility center. Ninety-five PCOs patients under 35 years of age, with primary infertility were randomized to an ovarian stimulation protocol consisting of either. GnRh antagonist (study group) or GnRH agonist (control group) after pretreatment with OCP. Coasting or GnRH agonist Trigger was used when estradiol level > or =3,000 pgr/ml in the control and study group, respectively. Both groups received 800 mg vaginal progesterone and 4 mg oral estradiol valerate for luteal phase support.\n There was no statistically significant difference in the age, body mass index, basal FSH, duration of infertility, the number of oocytes retrieved, the number of embryos transferred, Serum E2 levels on day of trigger, fertilization rate, chemical and clinical pregnancy rates between the two groups. None of the patients in the study group developed ovarian hyperstimulation syndrome (OHSS) compared with 22.2% of patients in the control group. Total duration of treatment and the number of HMG ampoules used were lower in the study group.\n Antagonist protocol and GnRH agonist trigger for ovulation whenever necessary has a similar cycle outcome to the GnRH-agonist protocol in OCP pretreated PCOs patients, with significantly reduced risk of OHSS.", "To compare the effects of oral contraceptive (OC) pill pretreatment in recombinant FSH/GnRH-antagonist versus recombinant FSH/GnRH-agonist stimulation in in vitro fertilization (IVF) patients, and to evaluate optimization of retrieval day.\n Prospective, randomized, multicenter study.\n Private practice and university centers.\n Eighty patients undergoing IVF who met the appropriate inclusion criteria.\n Four study centers recruited 80 patients. The OC regimen began on cycle days 2 to 4 and was discontinued on a Sunday after 14 to 28 days. The recombinant FSH regimen was begun on the following Friday. The GnRH-agonist group was treated with a long protocol; the GnRH-antagonist was initiated when the lead follicle reached 12 to 14 mm. When two follicles had reached 16 to 18 mm, hCG was administered.\n The primary outcome measures were the number of cumulus-oocyte complexes, day of the week for oocyte retrieval, and total dose and days of stimulation of recombinant FSH. Secondary efficacy variables included pregnancy and implantation rate; serum E(2) levels on stimulation day 1; serum E(2), P, and LH levels on the day of hCG administration; follicle size on day 6 and day of hCG administration; the total days of GnRH-analogue treatment; total days on OC; total days from end of OC to oocyte retrieval; and the cycle cancellation rate.\n Patient outcomes were similar for the days of stimulation, total dose of gonadotropin used, two-pronuclei embryos, pregnancy (44.4% GnRH-antagonist vs. 45.0% GnRH-agonist, P=.86) and implantation rates (22.2% GnRH-antagonist vs. 26.4% GnRH-agonist, P=.71). Oral contraceptive cycle scheduling resulted in 78% and 90% of retrievals performed Monday through Friday for GnRH-antagonist and GnRH-agonist. A one day delay in OC discontinuation and recombinant FSH start would result in over 90% of oocyte retrievals occurring Monday through Friday in both groups.\n The OC pretreatment in recombinant FSH/GnRH-antagonist protocols provides a patient-friendly regimen and can be optimized for weekday retrievals. No difference was seen in number of 2PN embryos, cryopreserved embryos, embryos transferred, implantation and pregnancy rates between the two stimulation protocols.", "To test whether ovarian stimulation for in-vitro fertilization (IVF) affects oocyte quality and thus chromosome segregation behaviour during meiosis and early embryo development, preimplantation genetic screening of embryos was employed in a prospective, randomized controlled trial, comparing two ovarian stimulation regimens.\n Infertile patients under 38 years of age were randomly assigned to undergo a mild stimulation regimen using gonadotrophin-releasing hormone (GnRH) antagonist co-treatment (67 patients), which does not disrupt secondary follicle recruitment, or a conventional high-dose exogenous gonadotrophin regimen and GnRH agonist co-treatment (44 patients). Following IVF, embryos were biopsied at the eight-cell stage and the copy number of 10 chromosomes was analysed in 1 or 2 blastomeres.\n The study was terminated prematurely, after an unplanned interim analysis (which included 61% of the planned number of patients) found a lower embryo aneuploidy rate following mild stimulation. Compared with conventional stimulation, significantly fewer oocytes and embryos were obtained following mild stimulation (P < 0.01 and < 0.05, respectively). Consequently, both regimens generated on average a similar number (1.8) of chromosomally normal embryos. Differences in rates of mosaic embryos suggest an effect of ovarian stimulation on mitotic segregation errors.\n Future ovarian stimulation strategies should avoid maximizing oocyte yield, but aim at generating a sufficient number of chromosomally normal embryos by reduced interference with ovarian physiology.", "This study evaluates the efficacy of a stimulation protocol with clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/cetrorelix and its effects on oocyte quality and endometrium. One hundred and twenty couples with male-factor infertility who were about to undergo their first intracytoplasmic sperm injection cycles were randomized into two groups. Sixty women were stimulated with the CC/hMG/cetrorelix protocol (cetrorelix group) and 60 received the buserelin long protocol (buserelin group). Fewer oocytes were recovered in the cetrorelix group than in the buserelin group (mean +/- standard deviation (SD): 11.1 +/- 4.0 vs. 17.3 +/- 5.8, p < 0.001); however, the percentages of metaphase II, metaphase I and germinal vesicle oocytes were similar between the two groups. Serum estradiol level was significantly lower in the cetrorelix than in the buserelin group (mean +/- SD: 2600.58 +/- 1189.11 vs. 3293.46 +/- 1221.49 pg/ml, p = 0.006), but the endometrial thickness was similar. The implantation rates (19.2% vs. 17.7%) and the pregnancy rates (41.7% vs. 40.0%) were similar between groups. The ampoules (mean +/- SD: 18.9 +/- 3.0 vs. 38.9 +/- 12.2, p < 0.001) and injections (mean +/- SD: 6.8 +/- 1.1 vs. 15.7 +/- 3.1, p < 0.001) of gonadotropin used were significantly lower in the cetrorelix group than in the buserelin group. No patients in either group developed a premature luteinizing hormone surge. The present study found no statistically significant difference between the two treatment modalities with regard to pregnancy rates.", "To investigate the efficacy of gonadotropin releasing hormone antagonist (GnRH) in poor responders undergoing in vitro fertilization.\n Ninety-six patients with poor ovarian response in previous treatment cycles were prospectively randomized into two groups. Forty-four patients were stimulated with GnRH antagonist multidose protocol and 45 patients received a standard long agonist protocol. Ovarian response was evaluated by transvaginal ultrasound and hormonal parameters. Cycle characteristics and treatment outcomes were statistically compared between groups.\n There was significantly reduced duration of stimulation and consumption of gonadotrophins in the antagonist group when compared to the agonist group. The estradiol concentrations on the day of human chorionic gonadotropin (hCG) injection, the number of oocytes retrieved, and the number of embryos transferred were similar for both groups. In the antagonist group, eight (18.1%) ongoing pregnancies were achieved and in the agonist group, ten (22.2%) clinical pregnancies were achieved but the difference was not statistically significant.\n The present study was not powered to detect clinically relevant differences between two protocols in outcomes such as pregnancy rate, with confidence.", "To compare the outcome of using gonadotropin-releasing hormone (GnRH) antagonists versus agonists in women with polycystic ovary disease (PCOD) who underwent controlled ovarian hyperstimulation (COH) for assisted reproductive techniques (ART).\n A total of 129 patients with PCOD were randomly allocated to undergo COH with a GnRH antagonist (59 patients) and GnRH agonist (leuprolide acetate) (70 patients) to prevent a premature luteinizing hormone (LH) surge. Assisted fertilization following oocyte retrieval and embryo transfer was performed.\n None of the cycles were cancelled due to a premature LH surge. There was no significant difference between the antagonist and agonist arms in the number of gonadotropin ampules consumed per cycle. However, in the antagonist arm a shorter duration of ovarian stimulation was recorded as compared to the agonist arm. Although similar numbers of oocytes was retrieved from both groups of patients, the quality of the oocytes, as measured by metaphase 2/total oocyte ratio, was lower in the antagonist arm as compared to the agonist arm. Pregnancy rates were 57.6% and 58.5% in the antagonist and agonist arms, respectively (p > 0.05). Implantation rates were not different (34.0% and 34.6%, respectively). The frequency of ovarian hyperstimulation syndrome also did not differ between the treatment groups (5% and 7.1%, respectively).\n The size of our study, on a specific subgroup of patients, does not allow a reliable conclusion regarding ART outcomefollowing the use of a GnRH antagonist versus agonist. Nevertheless, the protocol with the antagonist gave results that were as good as those of the protocol with the agonist in this PCOD patient population.", "Both gonadotropin-releasing hormone (GnRH) analogs and antagonists have been used for pituitary desensitization during controlled ovarian hyperstimulation (COH). We aimed to determine the minimum effective daily dose of GnRH antagonist in women undergoing COH. We also compared the efficiency of a GnRH antagonist and a GnRH agonist.\n Women undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer were divided into five groups: (1) cetrorelix 0.25 mg ( n = 86); (2) cetrorelix 0.2 mg ( n = 28); (3) cetrorelix 0.15 mg ( n = 30); (4) leuprolide acetate (LA) 0.5 mg/day ( n = 58); (5) single half-dose LA depot 1.88 mg ( n = 49). Cetrorelix was administered daily from menstrual day 8 until the day of human chorionic gonadotropin administration. LA or LA depot was started on day 21 of the previous menstrual cycle.\n We observed lower gonadotropin (Gn) dosages, estradiol (E2) levels and reduced risk of ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist groups. A higher risk of luteinizing hormone (LH) surge was noted in cetrorelix 0.2 and 0.15 mg groups. Gn dosages (IU)/E2 levels (pg/mL) in each group were: (1) 1,949.4/1,191.1; (2) 1,869.6/1,010.8; (3) 1,856.7/1,023.6; (4) 2,184.5/1,323.6; and (5) 2,103.5/1,313.5, respectively. LH/OHSS risks were: (1) 3.5%/5.8%; (2) 7.1%/3.6%; (3) 13.3%/3.3%; (4) 3.4%/8.6%; and (5) 2%/8.2%, respectively. Number of oocytes/embryos/grade I, II embryos were: (1) 9.4/7.9/5.8; (2) 7.5/4.2/3.6; (3) 6.3/4.1/3.1; (4) 12.3/8.9/6.6; and (5) 11.8/8.4/6.1, respectively. There was no significant difference in terms of clinical outcomes between groups 1, 4 and 5, except for higher abortion rates (AR) in group 1. Pregnancy rate (PR)/implantation rate (IR) ratios in groups 1, 4, and 5 were statistically higher than those in groups 2 and 3. Chemical PR/IR/AR were: (1) 30.2%/5.9%/7%; (2) 21.4%/5.1%/7.1%; (3) 16.7%/4.1%/10%; (4) 32.8%/5.5%/8.6%; and (5) 30.6%/5.7%/8.2%, respectively.\n The lowest effective dosage of cetrorelix for pituitary desensitization during COH luteolysis is 0.25 mg, resulting in a comparable PR but a higher AR when compared with GnRH agonist.", "The aim of this study was to evaluate the response to treatment in a group of patients undergoing IVF and randomised to receive GnRH-antagonist or the GnRH-agonist. The endpoints were the pattern of follicular growth, the maturity of the oocytes collected, the embryo quality and the pregnancy outcome.\n A total of 136 patients undergoing IVF were included. Sixty-seven patients were allocated to the GnRH antagonist and 69 patients to the GnRH agonist. GnRH antagonist was administered when the leading follicle reached a diameter of 12-14 mm. GnRH agonist was administered in a long luteal protocol.\n The mean numbers of oocytes retrieved and mature oocytes were significantly higher in the agonist than in the antagonist group (p < 0.02 and p < 0.01, respectively). Embryo quality, implantation rate, clinical pregnancy rates, ongoing pregnancy rate and miscarriage rate were similar in both groups.\n Better follicular growth and oocyte maturation are achieved with GnRH agonist treatment. However, both regimens seem to have similar efficacy in terms of implantation and pregnancy rates. Further studies clarifying the effect of the GnRH antagonist on ovarian function are needed, as well as a clear definition of the best period of the follicular phase for the GnRH antagonist administration.", "To assess the efficacy, safety, and local tolerance of ganirelix acetate for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH).\n Phase III, multicenter, open-label randomized trial.\n In vitro fertilization (IVF) centers in North America.\n Healthy female partners (n = 313) in subfertile couples for whom COH and IVF or intracytoplasmic sperm injection were indicated.\n Patients were randomized to receive one COH cycle with ganirelix or the reference treatment, a long protocol of leuprolide acetate in conjunction with follitropin-beta for injection.\n Number of oocytes retrieved, pregnancy rates, endocrine variables, and safety variables.\n The mean number of oocytes retrieved per attempt was 11.6 in the ganirelix group and 14.1 in the leuprolide group. Fertilization rates were 62.4% and 61.9% in the ganirelix and leuprolide groups, respectively, and implantation rates were 21.1% and 26.1%. Clinical and ongoing pregnancy rates per attempt were 35.4% and 30.8% in the ganirelix group and 38.4% and 36.4% in the leuprolide acetate group. Fewer moderate and severe injection site reactions were reported with ganirelix (11.9% and 0.6%) than with leuprolide (24.4% and 1.1%).\n Ganirelix is effective, safe, and well tolerated. Compared with leuprolide acetate, ganirelix therapy has a shorter duration and fewer injections but produces a similar pregnancy rate.", "To study if luteal E(2) pre-treatment before GnRH antagonist protocol improves IVF/ICSI outcomes compared with standard long GnRH agonist protocol.\n A prospective, randomized and controlled study.\n ART center of a state public hospital\n Two hundred twenty infertile women underwent IVF/ICSI treatments.\n Participants received oral Estradiol Valerate 4 mg/day preceding the IVF cycle from day 21 until day 2 of next cycle before GnRH antagonist protocol (E(2) pre-treatment group n=109) or received standard long GnRH agonist protocol as control group (n=111).\n Number of oocytes collected, MII oocytes, fertilization, implantation, live birth and early pregnancy rate, and hormone profiles.\n E(2) pre-treatment exerted a significant suppressive effect on FSH but not LH secretion compared with basal FSH and LH levels. In E(2) pre-treatment group serum LH level was significantly higher during COH and serum P was also significantly higher on the day of HCG injection compared with control group. Five patients from E(2) pre-treatment group had elevated LH at all time (>or= 10 IU/L) and also a concomitantly high P (>1 ng/mL). Two of the five women achieved pregnancy but had early pregnancy loss. Overall, IVF/ICSI outcomes such as implantation, clinical pregnancy and live birth rates were similar between E(2) pre-treatment and control groups.\n Luteal E(2) pre-treatment before GnRH antagonist protocol significantly increases serum LH level and incidence rate of premature LH but no significant effect is observed on implantation, clinical pregnancy, live birth and early pregnancy loss rates compared with long GnRH agonist protocol. However, more studies in large numbers of cycles are needed to confirm that increased serum LH level by E(2) pre-treatment during COH has no negative effect on the IVF/ICSI outcomes.", "An open label, randomized, multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH. Normo-ovulatory women (n = 74) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate (n = 25) before ovarian stimulation with recombinant human FSH (r-hFSH) or with cetrorelix 3 mg on stimulation day 7 (with (n = 25) or without (n = 24) r-hLH 150 IU on days 7-10). The main outcome measures were the number of metaphase II (MII) oocytes retrieved; secondary efficacy end-points; adverse events (AE) and other safety measures. There were no significant differences between groups for MII oocytes retrieved, duration of stimulation, total r-hFSH dose and pregnancy rates. The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups. The majority of AE were mild to moderate in severity. Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety, although cetrorelix has the advantage of typically requiring only one injection.", "Patients with polycystic ovary syndrome (PCOS) may need a longer period of pituitary downregulation to suppress the elevated serum LH and androgen levels effectively during IVF treatment using the GnRH agonist long protocol. We proposed a stimulation protocol incorporating Diane-35 and GnRH antagonist (Diane/cetrorelix protocol) and compared it with the GnRH agonist long protocol for PCOS patients.\n Part I of the study was an observational pilot study to evaluate the hormonal change as a result of the Diane/cetrorelix protocol (n = 26). Part II of the study was a prospective randomized study comparing the Diane/cetrorelix protocol (n = 25) and the GnRH agonist long protocol (n = 24). In the Diane/cetrorelix protocol, patients were pre-treated with three cycles of Diane-35, followed by 0.25 mg of cetrorelix on cycle day 3. From day 4, cetrorelix and gonadotrophin were administered concomitantly until the day of HCG injection.\n Serum LH, estradiol and testosterone levels were suppressed comparably in both protocols at the start of gonadotrophin administration. Serum LH was suppressed at constant levels without a premature LH surge in the Diane/cetrorelix protocol. The clinical results for both protocols were comparable, with significantly fewer days of injection, lower amounts of gonadotrophin used and lower estradiol levels on the day of HCG injection following the Diane/cetrorelix protocol. Furthermore, there was no significant difference in clinical pregnancy outcome between the two stimulation protocols.\n The Diane/cetrorelix protocol has a similar pregnancy outcome to the GnRH agonist long protocol for women with PCOS undergoing IVF treatment.", "To determine which protocols work better between cetrorelix and long protocols in older patients in a randomized controlled study.\n A controlled randomized study in a single private IVF center.\n Infertile women referred to a private IVF center.\n Five hundred sixty-four women 40 years or older undergoing IVF.\n At their first IVF cycle, the women were randomized into two study groups using a computer-generated number sequence: 281 cases were treated with the cetrorelix protocol, and 283 patients were treated with a long protocol for controlled ovarian hyperstimulation.\n Days of stimulation, E(2) on the day of hCG administration, amount of FSH administered, number of oocytes yielded, number of embryos obtained, pregnancy rate, and implantation rate.\n Patients treated with the long protocol showed a significantly higher number of oocytes retrieved and a higher pregnancy rate for both the cycle and transfer with respect to the cetrorelix protocol patients. The other parameter evaluated did not show any statistically significant differences.\n Our study showed that the long protocol performed better in older women than the cetrorelix protocol and that the GnRH antagonist may be detrimental in older women.", "To assess safety and efficacy of cetrorelix utilisation in controlled ovarian stimulation (COS).\n Phase III, randomized, single center study of 131 patients undergoing COS and IVF with or without ICSI, in a University affiliated Hospital. Sixty-six patients were allocated to the protocol with antagonist and 65 to the agonist protocol arm. The Student's t-test, the Mann-Whitney test and the chi-square test were applied as required, using SPSS for Windows with a two-sided 5% significance level.\n The mean (+/-S.D.) duration of stimulation was 9.5+/-1.7 days in the antagonist group and 10.6+/-2.1 days in the agonist group (P=0.02). The mean (+/-S.D.) duration of suppression was 4.6+/-1.3 days in the antagonist group and 27.3+/-5.2 days in the agonist group (P<0.0001). No significant differences were noted in other outcome measures: amount of rFSH required, estradiol level on hCG day, number of follicles>or=15 mm and endometrial thickness on oocyte retrieval day, number of oocytes retrieved, fertilization rate and number of OHS cases. Clinical pregnancy rates per-attempt and per-transfer were 15.1% and 17.0% in the antagonist group and 16.9% and 20.0% in the agonist group (P=0.79 and 0.71, respectively).\n GnRH antagonists are an effective, safe and well tolerated alternative to agonists for COS.", "This is the first published report of a prospective, randomized, controlled trial comparing a fixed, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders undergoing IVF.\n Sixty-six poor responders were randomized into two groups: the study group received 0.25 mg of cetrorelix daily starting on day 6 of stimulation; the control group received 600 microg of buserelin acetate daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a fixed dose of recombinant FSH (300 IU daily) for stimulation.\n There were no significant differences in the cycle cancellation rates, duration of stimulation, consumption of gonadotrophins, and mean numbers of mature follicles, oocytes and embryos obtained. The implantation rates were similar, but the number of embryos transferred was significantly higher for the antagonist group (2.32 +/- 0.58 versus 1.50 +/- 0.83; P = 0.01). The pregnancy rates were also higher in the antagonist group, but the difference was not statistically significant.\n A fixed multi-dose GnRH antagonist protocol is feasible for patients who are poor responders on a long agonist protocol; however, our study failed to demonstrate an overall improvement in ovarian responsiveness. Clinical outcomes may be improved by developing more flexible antagonist regimens, an approach that requires further evaluation.", "To compare outcome following in vitro fertilization-embryo transfer (IVF-ET) using controlled ovarian hyperstimulation (COH) regimens using either the gonadotropin-releasing hormone (GnRH) agonist leuprolide acetate vs the GnRH antagonist ganirelix.\n Women needing IVF for conception were randomly assigned to 300 IU of gonadotropins with ganirelix used in the follicular phase when a follicle with a 14 mm average diameter was attained vs a regimen using leuprolide acetate from the mid-luteal phase of the previous cycle.\n There were no differences found in clinical, ongoing, delivered pregnancy rates or implantation rates between groups.\n The use of GnRH antagonists do not seem to reduce IVF outcome compared to using GnRH agonists in COH regimens.", "To compare the clinical pregnancy rate in recipients of oocytes from donors treated with leuprorelin + human menopausal gonadotropins (hMG) with that obtained when the donors were treated with ganirelix + recombinant follicle-stimulating hormone (rFSH). The secondary aim was to compare the donors' response to the two treatments.\n A prospective, randomized, comparative study was conducted between January 2005 and November 2006 in a private hospital. Donors were randomized to receive a long protocol of leuprorelin + hMG (group DI) or ganirelix + rFSH (group DII). Their respective recipients were randomized to group RI or group RII, respectively.\n The characteristics of the donors were similar in both groups. More cycles were cancelled in group DI than in group DII (28.1% vs. 2.5%; p < 0.05). Compared with donors in group DII, the donors in group DI required a significantly higher dose of gonadotropins (2794 +/- 957 U vs. 1777 +/- 1043 U; p < 0.05) and more days of stimulation (11.7 +/- 2.3 vs. 9.5 +/- 1.5; p < 0.05); they also yielded fewer oocytes (15.0 +/- 6.1 vs. 17.9 +/- 8.6; p < 0.05). There were no differences in the characteristics of the recipients, in the fertilization rate or in the number of embryos transferred. The quality of transferred embryos was better in group RI (8.0 +/- 1.2 vs. 7.5 +/- 1.6; p < 0.05), and this group also achieved a better pregnancy rate per embryo transfer than did group RII (62.3% vs. 48.4%; p < 0.05).\n Treating oocyte donors with leuprorelin + hMG produces among recipients a greater probability of clinical pregnancy per embryo transfer than when donors are treated with ganirelix + rFSH; however, more cycles are cancelled and the former treatment is more unpleasant for donors.", "In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.", "Mild in-vitro fertilisation (IVF) treatment might lessen both patients' discomfort and multiple births, with their associated risks. We aimed to test the hypothesis that mild IVF treatment can achieve the same chance of a pregnancy resulting in term livebirth within 1 year compared with standard treatment, and can also reduce patients' discomfort, multiple pregnancies, and costs.\n We did a randomised, non-inferiority effectiveness trial. 404 patients were randomly assigned to undergo either mild treatment (mild ovarian stimulation with gonadotropin-releasing hormone [GnRH] antagonist co-treatment combined with single embryo transfer) or a standard treatment (stimulation with a GnRH agonist long-protocol and transfer of two embryos). Primary endpoints were proportion of cumulative pregnancies leading to term livebirth within 1 year after randomisation (with a non-inferiority threshold of -12.5%), total costs per couple up to 6 weeks after expected date of delivery, and overall discomfort for patients. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Clinical Trial, number ISRCTN35766970.\n The proportions of cumulative pregnancies that resulted in term livebirth after 1 year were 43.4% with mild treatment and 44.7% with standard treatment (absolute number of patients=86 for both groups). The lower limit of the one-sided 95% CI was -9.8%. The proportion of couples with multiple pregnancy outcomes was 0.5% with mild IVF treatment versus 13.1% (p<0.0001) with standard treatment, and mean total costs were 8333 euros and 10745 euros, respectively (difference 2412 euros, 95% CI 703-4131). There were no significant differences between the groups in the anxiety, depression, physical discomfort, or sleep quality of the mother.\n Over 1 year of treatment, cumulative rates of term livebirths and patients' discomfort are much the same for mild ovarian stimulation with single embryos transferred and for standard stimulation with two embryos transferred. However, a mild IVF treatment protocol can substantially reduce multiple pregnancy rates and overall costs.", "To determine whether there are any differences in the incidence of ovarian hyperstimulation syndrome (OHSS) and implantation rates in high-risk patients undergoing IVF using a protocol consisting of GnRH agonist trigger after cotreatment with GnRH antagonist or hCG trigger after dual pituitary suppression protocol.\n Prospective randomized controlled trial.\n University-based tertiary fertility center.\n Sixty-six patients under 40 years of age with polycystic ovarian syndrome, polycystic ovarian morphology, or previous high response undergoing IVF.\n Patients were randomized to an ovarian stimulation protocol consisting of either GnRH agonist trigger after cotreatment with GnRH antagonist (study group) or hCG trigger after dual pituitary suppression with a GnRH agonist (control group). Both groups received luteal phase and early pregnancy supplementation with IM progesterone (P), and patients in the study group also received E(2) patches and their doses were adjusted according to the serum levels.\n Incidence of OHSS and implantation rate.\n None of the patients in the study group developed any form of OHSS compared with 31% (10/32) of the patients in the control group. There were no significant differences in the implantation (22/61 [36.0%] vs. 20/64 [31.0%]), clinical pregnancy (17/30 [56.7%] vs. 15/29 [51.7%]), and ongoing pregnancy rates (16/30 [53.3%] vs. 14/29 [48.3%]) between the study and control groups, respectively.\n The use of a protocol consisting of GnRH agonist trigger after GnRH antagonist cotreatment combined with adequate luteal phase and early pregnancy E(2) and P supplementation reduces the risk of OHSS in high-risk patients undergoing IVF without affecting implantation rate.", "BACKGROUND The optimal time for GnRH antagonist initiation is still debatable. The purpose of the current randomized controlled trial is to provide endocrine and follicular data during ovarian stimulation for IVF in patients with polycystic ovarian syndrome (PCOS) treated either with a long GnRH agonist scheme or a fixed day-1 GnRH antagonist protocol. METHODS Randomized patients in both groups (antagonist: n = 26; long agonist: n = 52) received oral contraceptive pill treatment for three weeks and a starting dose of 150 IU of follitropin beta. The primary outcome was E(2) level on Day 5 of stimulation, while secondary outcomes were follicular development, LH during ovarian stimulation and progesterone levels. RESULTS Significantly more follicles on days 5, 7 and 8 of stimulation, significantly higher estradiol (E(2)) levels on days 1, 3, 5, 7 and 8 and significantly higher progesterone levels on days 1, 5 and 8 of stimulation were observed in the antagonist when compared with the agonist group. E(2) was approximately twice as high in the antagonist when compared with the agonist group on day 5 of stimulation (432 versus 204 pg ml(-1), P lt; 0.001). These differences were accompanied by significantly lower LH levels on days 3 and 5 and significantly higher LH levels on days 1, 7 and 8 of stimulation in the antagonist when compared with the agonist group. CONCLUSIONS In PCOS patients undergoing IVF, initiation of GnRH antagonist concomitantly with recombinant FSH is associated with an earlier follicular growth and a different hormonal environment during the follicular phase when compared with the long agonist protocol.", "Embryological and clinical efficacy of gonadotropin-releasing hormone (GnRH) antagonist and agonist stimulation protocols in non-obese women with polycystic ovarian syndrome (PCOS) were compared.\n A prospective randomized study. Setting: Medical University Hospital. Patients: 70 infertile PCOS patients; 33 in GnRH antagonist and 37 in GnRH agonist group.\n Similar mature metaphase II oocyte rate (76% vs. 76%) was observed in both protocols. Optimal pronuclear morphology zygotes dominated in both groups (64% vs. 66%). Transferred embryo quality did not differ in both protocols. No significant differences between both protocols were found in delivery rate (p = 0.481), pregnancy rate (p = 0.810), multiple pregnancy rate (p = 0.501), miscarriage rate (p = 0.154), fertilization rate (p = 0.388) and implantation rate (p = 1.000). Duration of stimulation and total follicle-stimulating hormone (FSH) dose were significantly lower in GnRH antagonist protocol (p = 0.0005).\n GnRH antagonist and agonist protocols in non-obese PCOS patients yield similar embryological and clinical outcomes. Shorter duration of treatment and lower FSH requirement in GnRH antagonist group may be financially beneficial and therefore attractive for patients.", "This randomized controlled trial was designed to assess the impact of oral contraceptive (OC) scheduling with a GnRH antagonist (ganirelix) regimen on the ovarian response of women undergoing recombinant FSH (rFSH) stimulation for IVF, compared with a non-scheduled ganirelix regimen and a long GnRH agonist (nafarelin) protocol.\n A total of 110 women was treated with an OC and ganirelix, 111 with ganirelix alone and 111 with nafarelin. The OC (containing 30 microg ethinylestradiol/150 microg desogestrel) was taken for 14-28 days and stopped 2 days prior to the start of rFSH treatment. Primary efficiency parameters were the number of cumulus-oocyte complexes (per attempt) and the number of grade 1 or 2 embryos (per attempt).\n In terms of follicular growth and hormone profiles, the OC-scheduled antagonist regimen mimicked the agonist regimen rather than the (non-scheduled) GnRH antagonist regimen. In the OC-scheduled GnRH antagonist group and the nafarelin group (versus the non-scheduled antagonist group), pituitary suppression was more profound at the start of stimulation (P < or = 0.001), there was a slower start of follicular growth (P < or = 0.001), longer stimulation was required (11.7 and 10.3 days respectively versus 9.4; P < or = 0.001), and more rFSH was used (2667 and 2222 IU versus 1966 IU; P < or = 0.001). In the three groups, the number of oocytes was similar (13.1, 12.9 and 11.5 respectively; not significant) as well as the number of good quality embryos (5.1, 5.7 and 5.0 respectively; not significant).\n OC treatment prior to the rFSH/ganirelix regimen can be successfully applied to schedule patients, although more days of stimulation and more rFSH are required than with a non-scheduled GnRH antagonist regimen.", "To evaluate the results of gonadotropin-releasing hormone agonist (GnRHa) and gonadotropin-releasing hormone antagonist (GnRHant) use in two demographically matched groups of normoresponder in-vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI) patients in a prospective study.\n We randomised 93 patients undergoing IVF/ICSI between May 2005 and August 2006. Patients with IVF indications were included except for those with polycystic ovary syndrome or azoospermia, women older than 38 years and those with follicle-stimulating hormone (FSH) > or =10 IU/ml. Patients were stimulated with standard 225 IU recombinant FSH. In Group I (n=45) a daily dose of GnRHant cetrorelix acetate 0.25 mg was administered when follicles reached a diameter of > or =14 mm. Group II (n=48) patients were desensitised with the GnRHa, leuprolide acetate, in a long protocol. Human chorionic gonadotropin (hCG) was administered when at least three follicles of 18 mm in diameter were observed. Oocyte retrieval was scheduled 36 hours following hCG administration and embryos were transferred on day 3 after oocyte retrieval.\n The two groups were homogenous for age, infertility duration, basal FSH and serum oestradiol (E2) (P=0.537, P=0.911, P=0.103 and P=0.733, respectively). In Group II (the GnRHa group) more antral follicles (P<0.001), a longer induction duration (P=0.017) and higher peak E2 levels (P<0.001) were observed. No differences were observed in the number of oocytes retrieved (P=0.749), embryos achieved and transferred (P=0.677), or fertilisation rates (P=0.839) between the two groups. There was no statistically significant difference between groups in clinical pregnancy rates, cycle cancellation and ovarian hyperstimulation (P=0.437, P=0.109 and P=0.415, respectively).\n GnRHant and GnRHa provide comparable results in normoresponder patients, while GnRHant allows a greater flexibility in their treatment.", "This randomized controlled study compared the effectiveness of a gonadotrophin releasing hormone (GnRH) antagonist protocol with or without oral contraceptive (OC) pretreatment on the number of oocytes retrieved in IVF or intracytoplasmic sperm injection (ICSI) patients. Sixty-four patients were randomized to start recombinant human FSH (r-hFSH) on day 2 or 3 after OC withdrawal (OC group) or on day 2 of a natural cycle (control group). From stimulation day 6 onwards, all patients were treated with daily (0.5 mg/ml) GnRH antagonist (Antide). OC pretreatment resulted in significantly lower starting concentrations of FSH, LH and oestradiol (P < 0.001) and a thinner endometrium (P < 0.0001). In the early stimulation period, fewer large follicles were found after OC pretreatment, leading to a significantly extended stimulation period (11.6 versus 8.7 days, P < 0.0001) with more follicles on the day of recombinant human chorionic gonadotrophin administration (15.4 versus 12.5, P = 0.02) and more oocytes retrieved (13.5 versus 10.2, P < 0.001) as compared with the control group. GnRH antagonist regimen, pretreated with OC, prevented the early endogenous FSH rise and improved follicular homogeneity, resulting in more oocytes. As a consequence of the extended treatment period, more rhFSH was required.", "To compare follicular fluid (FF) anti-Müllerian hormone (AMH) and inhibin B concentrations for GnRH agonist (GnRH-a) and GnRH antagonist cycles and to determine the correlations between FF AMH or inhibin B concentrations and controlled ovarian hyperstimulation (COH) outcomes.\n Prospective comparative study.\n University hospital.\n Eighty-seven women who underwent COH cycles, either in the GnRH-a long-protocol group (n = 43) or the GnRH antagonist multiple-dose flexible-protocol group (n = 44).\n Follicular fluid was obtained from dominant follicles during oocyte retrieval, and FF AMH, inhibin B, E(2), and P concentrations were measured. Serum levels of AMH and inhibin B also were assessed on the day of oocyte retrieval.\n Follicular fluid AMH and inhibin B concentrations.\n Concentrations of serum AMH and inhibin B and of FF AMH, inhibin B, E(2), and P were similar in the two groups. Follicular fluid AMH levels were found to be significantly correlated with age, gonadotropin dose, number of follicles on hCG day, and number of oocytes retrieved.\n Our results suggest that there is no significant difference in follicular microenvironment in terms of AMH and inhibin B secretion between GnRH-a and GnRH antagonist protocols and that FF AMH is a marker that reflects ovarian reserve and response to COH.", "This prospective randomized study was performed to compare the efficacy of GnRH antagonist multiple-dose protocol (MDP) with or without oral contraceptive pill (OCP) pretreatment and GnRH agonist low-dose long protocol (LP) in 82 patients undergoing IVF/intracytoplasmic sperm injection (ICSI). GnRH antagonist MDP with OCP pretreatment was at least as effective as GnRH agonist low-dose LP in low responders, and can benefit the low responders by reducing the amount of FSH and the number of days of stimulation required for follicular maturation.", "To provide a treatment for particular condition that is the most effective treatment with the least risk and cost for the patient we compared the efficacy of using clomiphene 100 mg + delayed low dose gonadotropin + flexible GnRH antagonist administration for ovarian stimulation protocol and GnRH agonist + gonadotropin for stimulation protocol in IVF outcome.\n Clinical outcome of 243 women with regularly menstruation who were candidate for IVF. They had undergone stimulation with GnRH agonist and gonadotropin (group A) or clomiphene citrate, gonadotropin and GnRH antagonist (group B). Main outcome was ongoing pregnancy.\n There were no significant difference in mean age, cause of infertility, basal FSH, BMI, duration of infertility, endometrial thickness on the day HCG administration in two groups. The number of recovered oocytes, obtained embryos, transferred embryos, peak of estradiol on the day HCG administration and OHSS were significantly higher in group A. Significantly more patients in control group had embryos for cryopreservation. There were no significant difference in clinical pregnancy rate and ongoing pregnancy rate between two groups.\n Clomiphene + delayed low dose gonadotropin + flexible GnRH - antagonist stimulation is an acceptable alternative protocol for IVF in patients with regularly menstruation.", "To confirm the value of a single dose of 3 mg of cetrorelix in preventing the occurrence of premature LH surges.\n Multicenter randomized, prospective study.\n Reproductive medicine units.\n Infertile patients undergoing ovarian stimulation for IVF-ET.\n A single dose of 3 mg of cetrorelix (Cetrotide; ASTA Medica, Frankfurt, Germany) (115 patients) was administered in the late follicular phase. A depot preparation of triptorelin (Decapeptyl; Ipsen-Biotech, Paris, France) was chosen as a control agent (39 patients). Ovarian stimulation was conducted with hMG (Menogon; Ferring, Kiel, Germany).\n Premature LH surges (LH level >10 IU/L), progesterone level greater than 1 ng/L, and IVF results.\n No LH surge occurred after cetrorelix administration. The patients in the cetrorelix group had a lower number of oocytes and embryos. The percentage of mature oocytes and fertilization rates were similar in both groups, and the pregnancy rates were not statistically different. The length of stimulation, number of hMG ampules administered, and occurrence of the ovarian hyperstimulation syndrome were lower in the cetrorelix group. Tolerance of cetrorelix was excellent.\n A cetrorelix single-dose protocol prevented LH surges in all patients studied. It compares favorably to the \"long protocol\" and could be a protocol of choice in IVF-ET." ]

[ "7980301" ]

[ "A safer and more effective treatment regimen for eclampsia." ]

[ "In a prospective controlled trial 91 consecutive women with eclampsia were randomly allocated either to a magnesium sulphate and nifedipine regime or to a lytic cocktail and nifedipine group. The type and severity of disease, details of labour and delivery, and the maternal and perinatal outcomes and complications related to the 2 treatment regimens were compared. Recurrence of fits, aspiration pneumonia and sudden hypotension were significantly reduced when patients were treated with the new magnesium sulphate and nifedipine regimen compared with the lytic cocktail plus nifedipine regimen. No patient treated with the new regimen died or had respiratory depression; in the other group there were 2 maternal deaths plus 1 case of severe hypoxic brain damage. No difference was observed in duration of labour or mode of delivery. Perinatal mortality was significantly lower in the magnesium sulphate plus nifedipine treated group. The synergistic action of magnesium sulphate and nifedipine in the dosage employed in this study may be used to reduce maternal and perinatal mortality and morbidity in women with eclampsia." ]

[ "20854384", "19734396", "14633804", "17392542", "16549460", "17563345", "17718288", "16634838" ]

[ "Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-blind clinical trial.", "Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial.", "Cinnamon improves glucose and lipids of people with type 2 diabetes.", "The effect of cinnamon on A1C among adolescents with type 1 diabetes.", "Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients.", "Effect of cinnamon on glucose and lipid levels in non insulin-dependent type 2 diabetes.", "The effect of cinnamon cassia powder in type 2 diabetes mellitus.", "Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2." ]

[ "To determine the blood glucose lowering effect of cinnamon on HbA1c, blood pressure and lipid profiles in people with type 2 diabetes.\n 58 type 2 diabetic patients (25 males and 33 females), aged 54.9 ± 9.8, treated only with hypoglycemic agents and with an HbA1c more than 7% were randomly assigned to receive either 2g of cinnamon or placebo daily for 12 weeks.\n After intervention, the mean HbA1c was significantly decreased (P<0.005) in the cinnamon group (8.22% to 7.86%) compared with placebo group (8.55% to 8.68%). Mean systolic and diastolic blood pressures (SBP and DBP) were also significantly reduced (P<0.001) after 12 weeks in the cinnamon group (SBP: 132.6 to 129.2 mmHg and DBP: 85.2 to 80.2 mmHg) compared with the placebo group (SBP: 134.5 to 134.9 mmHg and DBP: 86.8 to 86.1 mmHg). A significant reduction in fasting plasma glucose (FPG), waist circumference and body mass index (BMI) was observed at week 12 compared to baseline in the cinnamon group, however, the changes were not significant when compared to placebo group. There were no significant differences in serum lipid profiles of total cholesterol, triglycerides, HDL and LDL cholesterols neither between nor within the groups.\n Intake of 2g of cinnamon for 12 weeks significantly reduces the HbA1c, SBP and DBP among poorly controlled type 2 diabetes patients. Cinnamon supplementation could be considered as an additional dietary supplement option to regulate blood glucose and blood pressure levels along with conventional medications to treat type 2 diabetes mellitus.\n © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.", "Multiple trials in the past have shown conflicting results of whether cinnamon lowers glucose or hemoglobin A1C (HbA1C). The purpose of this study was to determine whether cinnamon lowers HbA1C in patients with type 2 diabetes. I performed a randomized, controlled trial to evaluate whether daily cinnamon plus usual care versus usual care alone lowers HbA1c.\n I randomized 109 type 2 diabetics (HbA1C >7.0) from 3 primary care clinics caring for pediatric, adult, and geriatric patients at a United States military base. Participants were randomly allocated to either usual care with management changes by their primary care physician or usual care with management changes plus cinnamon capsules, 1g daily for 90 days. HbA1c was drawn at baseline and 90 days and compared with intention-to-treat analysis. This study was approved by an institutional review board.\n Cinnamon lowered HbA1C 0.83% (95% CI, 0.46-1.20) compared with usual care alone lowering HbA1C 0.37% (95% CI, 0.15-0.59).\n Taking cinnamon could be useful for lowering serum HbA1C in type 2 diabetics with HbA1C >7.0 in addition to usual care.", "The objective of this study was to determine whether cinnamon improves blood glucose, triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol levels in people with type 2 diabetes.\n A total of 60 people with type 2 diabetes, 30 men and 30 women aged 52.2 +/- 6.32 years, were divided randomly into six groups. Groups 1, 2, and 3 consumed 1, 3, or 6 g of cinnamon daily, respectively, and groups 4, 5, and 6 were given placebo capsules corresponding to the number of capsules consumed for the three levels of cinnamon. The cinnamon was consumed for 40 days followed by a 20-day washout period.\n After 40 days, all three levels of cinnamon reduced the mean fasting serum glucose (18-29%), triglyceride (23-30%), LDL cholesterol (7-27%), and total cholesterol (12-26%) levels; no significant changes were noted in the placebo groups. Changes in HDL cholesterol were not significant.\n The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.", "The purpose of this study was to determine the effect of cinnamon on glycemic control in adolescents with type 1 diabetes.\n Using a prospective, double-blind, placebo-controlled design, 72 adolescent type 1 diabetic subjects were treated in an outpatient setting with cinnamon (1 g/day) or an equivalent-appearing placebo for 90 days. A1C, total daily insulin intake, and adverse events were recorded and compared between groups.\n There were no significant differences in final A1C (8.8 vs. 8.7, P = 0.88), change in A1C (0.3 vs. 0.0, P = 0.13), total daily insulin intake, or number of hypoglycemic episodes between the cinnamon and placebo arms.\n Cinnamon is not effective for improving glycemic control in adolescents with type 1 diabetes.", "In vitro and in vivo animal studies have reported strong insulin-like or insulin-potentiating effects after cinnamon administration. Recently, a human intervention study showed that cinnamon supplementation (1 g/d) strongly reduced fasting blood glucose concentration (30%) and improved the blood lipid profile in patients with type 2 diabetes. The objective of this study was to investigate the effects of cinnamon supplementation on insulin sensitivity and/or glucose tolerance and blood lipid profile in patients with type 2 diabetes. Therefore, a total of 25 postmenopausal patients with type 2 diabetes (aged 62.9 +/- 1.5 y, BMI 30.4 +/- 0.9 kg/m2) participated in a 6-wk intervention during which they were supplemented with either cinnamon (Cinnamomum cassia, 1.5 g/d) or a placebo. Before and after 2 and 6 wk of supplementation, arterialized blood samples were obtained and oral glucose tolerance tests were performed. Blood lipid profiles and multiple indices of whole-body insulin sensitivity were determined. There were no time x treatment interactions for whole-body insulin sensitivity or oral glucose tolerance. The blood lipid profile of fasting subjects did not change after cinnamon supplementation. We conclude that cinnamon supplementation (1.5 g/d) does not improve whole-body insulin sensitivity or oral glucose tolerance and does not modulate blood lipid profile in postmenopausal patients with type 2 diabetes. More research on the proposed health benefits of cinnamon supplementation is warranted before health claims should be made.", "nan", "Type 2 diabetes is a chronic metabolic disorder and the incidence of cardiovascular is increased two- to fourfold in its complications. Cinnamon is expected to have some degree of anti-diabetic efficacy without troublesome side effects. The objective of the present study was to investigate the anti-diabetic effect of cinnamon cassia powder in type 2 diabetic patients\n Sixty type 2 diabetic patients were randomized either 1.5 g/d of cinnamon cassia powder or placebo. Both groups were in combination with their current treatment (metformin or sulfonylurea) according to single blind randomized, placebo-control trial in a 12-week period. Efficacy was evaluated by HbA1c fasting plasma glucose, Lipid profile, BUN, creatinine, liver function test and adverse effects were recorded.\n After a 12-week period, HbA1c was decreased similarly in both groups from 8.14% to 7.76% in the cinnamon group and from 8.06% to 7.87% in the placebo group. This was not found statistically significantly different. However the proportion of patients achieving HbA1c < or = 7% was also greater in patients receiving cinnamon compared with patients receiving placebo, nevertheless, it was not found statistically significantly different (35% vs 15%, x2 = 3.14, p > 0.05). No significant intergroup differences were observed in lipid profile, fasting plasma glucose except in SGOT 27.1 (8.75) to 22.1 (5) in cinnamon group and 24.08 (8.5) to 23.63 (8.88) in the placebo group (p = 0.001).\n The cinnamon cassia powder 1.5 g/d did not have any significant difference in reducing fasting plasma glucose, HbA1c and serum lipid profile in type 2 diabetes patients who had mean fasting plasma glucose 154.40 +/- 24.72 mg/dl.", "According to previous studies, cinnamon may have a positive effect on the glycaemic control and the lipid profile in patients with diabetes mellitus type 2. The aim of this trial was to determine whether an aqueous cinnamon purified extract improves glycated haemoglobin A1c (HbA1c), fasting plasma glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triacylglycerol concentrations in patients with type 2 diabetes.\n A total of 79 patients with diagnosed diabetes mellitus type 2 not on insulin therapy but treated with oral antidiabetics or diet were randomly assigned to take either a cinnamon extract or a placebo capsule three times a day for 4 months in a double-blind study. The amount of aqueous cinnamon extract corresponded to 3 g of cinnamon powder per day.\n The mean absolute and percentage differences between the pre- and post-intervention fasting plasma glucose level of the cinnamon and placebo groups were significantly different. There was a significantly higher reduction in the cinnamon group (10.3%) than in the placebo group (3.4%). No significant intragroup or intergroup differences were observed regarding HbA1c, lipid profiles or differences between the pre- and postintervention levels of these variables. The decrease in plasma glucose correlated significantly with the baseline concentrations, indicating that subjects with a higher initial plasma glucose level may benefit more from cinnamon intake. No adverse effects were observed.\n The cinnamon extract seems to have a moderate effect in reducing fasting plasma glucose concentrations in diabetic patients with poor glycaemic control." ]

[ "2046107" ]

[ "Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group." ]

[ "To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension.\n Multicenter, randomized, double-blind, placebo-controlled.\n Community-based ambulatory population in tertiary care centers.\n 4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black.\n --Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d.\n Primary. Nonfatal and fatal (total) stroke. Secondary. Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures.\n Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87.\n In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000." ]

[ "20942667", "18580613", "20823434", "19020325" ]

[ "Antiretroviral treatment for children with peripartum nevirapine exposure.", "Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants.", "Reuse of nevirapine in exposed HIV-infected children after protease inhibitor-based viral suppression: a randomized controlled trial.", "Early antiretroviral therapy and mortality among HIV-infected infants." ]

[ "Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown.\n We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board.\n A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P=0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events.\n Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00307151.).", "Infants infected with HIV-1 perinatally despite single-dose nevirapine progress rapidly. Data on treatment outcome in sub-Saharan African infants exposed to single-dose nevirapine are urgently required. This feasibility study addresses efficacy of infant antiretroviral therapy in this setting.\n HIV-infected infants in Durban, South Africa, received randomized immediate or deferred (when CD4 cell count reached <20%) four-drug antiretroviral therapy (zidovudine/lamivudine/nelfinavir/nevirapine). Genotyping for non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was undertaken pre-antiretroviral therapy. Monthly follow-up to 1-year post-antiretroviral therapy included viral load, CD4 cell count and verbal/measured adherence monitoring.\n All 63 infants were exposed to single-dose nevirapine. Twenty-one out of 51 (39%) infants with baseline genotyping results had NNRTI resistance (most frequently Y181C; 20%). Forty-three infants were randomized to immediate antiretroviral therapy (ART): three withdrew pre-antiretroviral therapy; 36 out of 40 completed 1-year of ART. Twenty infants received deferred ART: 17 reached CD4 cell counts less than 20% (median d99) and 13 out of 17 started antiretroviral therapy in year 1. Verbal and measured adherence was 99% and 95%, respectively. One-year post-ART, 49 out of 49 (100%) infants had a viral load less than 400 copies/ml; 46 out of 49 (94%) had viral load less than 50 copies/ml. Ten infants (20%) required second-line ART due to virological failure or tuberculosis treatment, therefore 39 out of 49 (80%) achieved viral load less than 400 copies/ml by intention-to-treat. Time to viral load less than 50 copies/ml correlated with maternal CD4 cell count (r = -0.42; P = 0.005) and infant pre-ART viral load (r = 0.64; P < 0.001). NNRTI mutations had no significant effect on virological suppression. Infants starting immediate compared with deferred ART had fewer illness episodes (P = 0.003), but no significant difference in virological suppression.\n Excellent adherence and virological suppression are achievable in infants, despite high-frequency NNRTI mutations and rapid disease progression. Infants remain relatively neglected in roll-out programmes and ART provision must be expanded.", "Protease inhibitor (PI)-based therapy is recommended for infants infected with human immunodeficiency virus (HIV) who were exposed to nevirapine for prevention of mother-to-child HIV transmission. However, there are limitations of continuing PI-based therapy indefinitely and reuse of nevirapine has many advantages.\n To test whether nevirapine-exposed infants who initially achieve viral suppression with PI-based therapy can maintain viral suppression when switched to nevirapine-based therapy.\n Randomized trial conducted between April 2005 and May 2009 at a hospital in Johannesburg, South Africa, among 195 children who achieved viral suppression less than 400 copies/mL for 3 or more months from a cohort of 323 nevirapine-exposed children who initiated PI-based therapy before 24 months of age.\n Control group children continued to receive ritonavir-boosted lopinavir, stavudine, and lamivudine (n = 99). Switch group children substituted nevirapine for ritonavir-boosted lopinavir (n = 96).\n Children were followed up for 52 weeks after randomization. Plasma HIV-1 RNA of greater than 50 copies/mL was the primary end point. Confirmed viremia greater than 1000 copies/mL was used as a criterion to consider regimen changes for children in either group (safety end point).\n Plasma viremia greater than 50 copies/mL occurred less frequently in the switch group (Kaplan-Meier probability, 0.438; 95% CI, 0.334-0.537) than in the control group (0.576; 95% CI, 0.470-0.668) (P = .02). Confirmed viremia greater than 1000 copies/mL occurred more frequently in the switch group (0.201; 95% CI, 0.125-0.289) than in the control group (0.022; 95% CI, 0.004-0.069) (P < .001). CD4 cell response was better in the switch group (median CD4 percentage at 52 weeks, 34.7) vs the control group (CD4 percentage, 31.3) (P = .004). Older age (relative hazard [RH], 1.71; 95% CI, 1.08-2.72) was associated with viremia greater than 50 copies/mL in the control group. Inadequate adherence (RH, 4.14; 95% CI, 1.18-14.57) and drug resistance (RH, 4.04; 95% CI, 1.40-11.65) before treatment were associated with confirmed viremia greater than 1000 copies/mL in the switch group.\n Among HIV-infected children previously exposed to nevirapine, switching to nevirapine-based therapy after achieving viral suppression with a ritonavir-boosted lopinavir regimen resulted in lower rates of viremia greater than 50 copies/mL than maintaining the primary ritonavir-boosted lopinavir regimen.\n clinicaltrials.gov Identifier: NCT00117728.", "In countries with a high seroprevalence of human immunodeficiency virus type 1 (HIV-1), HIV infection contributes significantly to infant mortality. We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial.\n HIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage (the CD4 percentage) of 25% or more were randomly assigned to receive antiretroviral therapy (lopinavir-ritonavir, zidovudine, and lamivudine) when the CD4 percentage decreased to less than 20% (or 25% if the child was younger than 1 year) or clinical criteria were met (the deferred antiretroviral-therapy group) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age (the early antiretroviral-therapy groups). We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy.\n At a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P<0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P<0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy.\n Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. (ClinicalTrials.gov number, NCT00102960.)\n 2008 Massachusetts Medical Society" ]

[ "16034832", "16327491", "15746784", "16192503", "11518996", "11485528", "17318804" ]

[ "Randomized clinical trial of the effect of a saline-linked radiofrequency coagulator on blood loss during hepatic resection.", "How should transection of the liver be performed?: a prospective randomized study in 100 consecutive patients: comparing four different transection strategies.", "Sharp liver transection versus clamp crushing technique in liver resections: a prospective study.", "Hepatic resection by the Cavitron Ultrasonic Surgical Aspirator increases the incidence and severity of venous air embolism.", "[Surgical techniques in hepatic resections: Ultrasonic aspirator versus Jet-Cutter. A prospective randomized clinical trial].", "Randomized comparison of ultrasonic vs clamp transection of the liver.", "Randomized clinical trial of radiofrequency-assisted versus clamp-crushing liver resection." ]

[ "Use of a saline-linked radiofrequency coagulator (dissecting sealer) has been suggested to reduce blood loss during hepatic resection. A randomized clinical trial was conducted to assess the effects of using the device on the amount of blood loss.\n Patients scheduled to undergo hepatic resection were randomly assigned to either use of the dissecting sealer or the clamp crushing method. The primary outcome measure was blood loss during liver parenchymal division. Multivariate analysis was also performed.\n Ninety-four consecutive patients underwent hepatic resection and 40 patients were assigned to each group. There were no significant differences between the dissecting sealer and clamp crushing groups in blood loss during liver parenchymal division (median 373 versus 535 ml; P = 0.252) or total intraoperative blood loss (665 versus 733 ml; P = 0.450). Multivariate analysis revealed that use of the dissecting sealer offered no protection against blood loss compared with the clamp crushing method (odds ratio 1.17 (95 per cent confidence interval 0.39 to 3.53); P = 0.777), whereas number of resections, thoracotomy and type of resection had a significant effect.\n Use of a dissecting sealer offered no substantial benefit over the clamp crushing method in reducing blood loss during hepatic resection.", "To identify the most efficient parenchyma transection technique for liver resection using a prospective randomized protocol.\n Liver resection can be performed by different transection devices with or without inflow occlusion (Pringle maneuver). Only limited data are currently available on the best transection technique.\n A randomized controlled trial was performed in noncirrhotic and noncholestatic patients undergoing liver resection comparing the clamp crushing technique with Pringle maneuver versus CUSA versus Hydrojet versus dissecting sealer without Pringle maneuver (25 patients each group). Primary endpoints were intraoperative blood loss, resection time, and postoperative liver injury. Secondary end points included the use of inflow occlusion, postoperative complications, and costs.\n The clamp crushing technique had the highest transection velocity (3.9 +/- 0.3 cm/min) and lowest blood loss (1.5 +/- 0.3 mL/cm) compared with CUSA (2.3 +/- 0.2 cm/min and 4 +/- 0.7 mL/cm), Hydrojet (2.4 +/- 0.3 cm/min and 3.5 +/- 0.5 mL/cm), and dissecting sealer (2.5 +/- 0.3 cm/min and 3.4 +/- 0.4 mL/cm) (velocity: P = 0.001; blood loss: P = 0.003). Clamp crushing technique was associated with the lowest need for postoperative blood transfusions. The degree of postoperative reperfusion injury and complications were not significantly different among the groups. The clamp crushing technique proved to be most cost-efficient device and had a cost-saving potential of 600 to 2400 per case.\n The clamp crushing technique was the most efficient device in terms of resection time, blood loss, and blood transfusion frequency compared with CUSA, Hydrojet, and dissecting sealer, and proved to be also the most cost-efficient device.", "Parenchymal liver transection constitutes an important phase of liver resection. Serious intraoperative bleeding, together with injuries to vital structures of the liver remnant, can occur during this stage. A method of sharp liver parenchymal transection with scalpel is compared in a prospective randomized manner with the widely used clamp crushing technique.\n Patients scheduled for hepatectomy under selective hepatic vascular exclusion (N = 82) were allocated randomly to either the sharp transection group (n = 41) or the clamp crushing group (n = 41). Warm ischemic time, blood loss and transfusions, postoperative morbidity and mortality, and tumor-free margins were recorded in both groups and analyzed.\n When the sharp transection group was compared with the clamp crushing group, the two groups were similar in warm ischemic time (median 36 vs 34 minutes), total operative time (median 205 vs 211 minutes), intraoperative blood loss (median 500 vs 460 mL), blood transfusion requirements (median value 0 in both groups), and overall complication rate (44% vs 39%). However, sharp transection yielded better tumor-free margins compared with the clamp crushing technique (12 +/- 1.4 mm vs 8 +/- 1.5 mm, mean +/- SD, P < .05).\n Sharp liver parenchymal transection with a scalpel is equally safe in terms of blood loss and mortality compared with the clamp crushing method. Although it is a technically demanding method, requiring selective hepatic vascular occlusion, it may be recommended when the tumor-free margins are anticipated to be narrow.", "The Cavitron Ultrasonic Surgical Aspirator (CUSA) is an innovative tool for resecting hepatic parenchyma, which reduces intraoperative blood loss and perioperative morbidity. We designed this study to compare the incidence and severity of venous air embolism (VAE) detected via transesophageal echocardiography (TEE) during hepatic resection by using either the clamp-crushing method or the CUSA method. Fifty patients scheduled for hepatic resection were randomly assigned to receive hepatic resection by the clamp-crushing method (CC group) or by CUSA (CUSA group). After the induction of anesthesia, the TEE probe was inserted into the patient's esophagus. An independent anesthesiologist graded VAE shown in the 4-chamber view of TEE. All patients in the CUSA group showed VAE during hepatic resection and 44% of the patients had air embolism filling more than half the right heart diameter. In CC group, 68% of the patients showed VAE, which filled less than half the right heart diameter. There were no significant differences in hemodynamics and end-tidal CO2 partial pressure between the two groups. In conclusion, hepatic resection by CUSA increases the incidence and severity of VAE.\n This study demonstrated that venous air embolism during hepatic resection was more frequent and severe when using the Cavitron Ultrasonic Surgical Aspirator. Although we found no evidence of hemodynamic compromise, increased venous air embolism may increase the risk of paradoxical embolism in patients with liver cirrhosis.", "For all resection-techniques of liver tissue intra- and post-operative blood-loss remains an important problem. Two novel resection-techniques the ultrasound-aspirator (CUSA) and the water-jet dissector (Jet-Cutter) appear to offer significant advantages regarding this problem. Aim of the present prospective clinical study was the comparison of these dissection techniques.\n Prospective randomized study with the end points blood-loss, length of surgery, tissue trauma and long-term survival.\n Significant differences between both procedures with Jet-Cutter (n = 31) versus ultrasonic surgical aspirator CUSA (n = 30) were observed regarding length of resection and complete liver ischemia time (Pringle-time). Here significant advantages of the jet-cutter-technique were observed with 28 +/- 11 minutes length of resection versus 46 +/- 19 minutes and 29 +/- 12 minutes Pringle-time versus 39 +/- 16 minutes. Furthermore, significant fewer blood transfusions were required following jet-cutter-resection with a mean of 1.5 blood units vs. 2.5 blood units using the CUSA. No differences were observed regarding postoperative long-term survival.\n The jet-cutter-technique is a fast and safe surgical procedure for liver resections and offers an attractive therapeutic alternative for various indications in liver surgery.", "Hepatic parenchymal transection is a technical priority in liver surgery. The use of an ultrasonic dissector for hepatectomy may result in less blood loss than conventional clamp crushing.\n Randomized controlled trial.\n University teaching hospital.\n The 132 patients scheduled to undergo partial hepatectomies were randomly assigned to receive hepatic transection by ultrasonic dissector or by clamp crushing (66 patients by each method).\n All resections were performed with inflow occlusion and were guided ultrasonographically. Hepatectomies were graded according to a predefined system based on 6 criteria (blood loss, transection time, technical error, surgical margin, landmark appearance, and postoperative morbidity), each with 3 scores (lower scores indicating higher quality).\n Blood loss and hepatectomy grade.\n No difference was found between the ultrasonic and clamp groups in median blood loss (515 mL [range, 15-2527 mL] vs 452 mL [range, 17-1912 mL]; P =.63), transection time (61 minutes [range, 16-177 minutes] vs 54 minutes [range, 7-205 minutes]; P =.58), or transection speed (1.1 cm(2)/min [range, 0.4-4.0 cm(2)/min] vs 1.0 cm(2)/min [range, 0.4-3.0 cm(2)/min]; P =.90). Ultrasonic dissection caused more frequent histologically proven tumor exposure at the surgical margin (9 vs 3 patients; P =.09), incomplete appearance of landmark hepatic veins on the cut surface after anatomical resection (12 vs 4 patients; P =.03), and postoperative morbidity (20 vs 14 patients; P =.32) than did clamp crushing. The hepatectomies with clamp crushing had significantly higher grades than those with ultrasonic dissection (P =.05), as indicated by the lower median sum score (4.0 [range, 0-12] vs 5.0 [range, 0-19]; 95% confidence interval for difference, -2.0 to 0; P =.03). The transection method independently influenced hepatectomy grade (adjusted odds ratio = 3.06; 95% confidence interval, 1.35-6.92; P =.01).\n Ultrasonic dissection offers no reduction in blood loss compared with clamp crushing for transection of the liver. Clamp crushing results in a higher quality of hepatectomy and is therefore the option of choice.", "Surgical resection remains the treatment of choice for primary and secondary liver cancer. Complications are mainly related to blood loss. Radiofrequency-assisted liver resection (RF-R) has been proposed for parenchymal division as an alternative to clamp crushing in order to reduce blood loss.\n Fifty patients (median age 62 (range 30-82) years) undergoing hepatectomy were randomized to RF-R (24 patients) or the clamp-crushing method (26). In the RF-R group the resection plane was precoagulated by multiple insertion of a planar triple-cooled radiofrequency ablation needle, and then the parenchyma was sectioned using a scalpel.\n The two groups were well matched in terms of age, sex, liver disease and type of resection. There were no deaths. Eight in the RF-R group developed complications (abscess in six, biliary fistula in three and biliary stenosis in one) compared with none of those who had resection by the crush method (P < 0.001). Two patients with cirrhosis in each group developed decompensation. Blood transfusion was required in eight of 24 patients in the RF-R group and 13 of 26 in the clamp-crushing group (P = 0.079).\n RF-R allows parenchymal resection in a clean surgical field but is associated with a higher rate of postoperative complications than the clamp-crushing technique.\n (c) 2007 British Journal of Surgery Society Ltd." ]

[ "17668972", "12699051", "16170976", "18672987", "16881807", "3865818", "1107508", "17240933", "12691269", "18277739", "6980082", "2083478" ]

[ "Efficacy of an automated flossing device in different regions of the mouth.", "The efficacy of an essential oil antiseptic mouthrinse vs. dental floss in controlling interproximal gingivitis: a comparative study.", "Clinical trial of a novel interdental brush cleaning system.", "Comparison of the use of different modes of mechanical oral hygiene in prevention of plaque and gingivitis.", "Clinical efficacy of flossing versus use of antimicrobial rinses.", "Interproximal subgingival cleaning by dental floss and the toothpick.", "Evaluation of cleansing devices in the maintenance of interproximal gingival health.", "A clinical investigation of the efficacy of three different treatment regimens for the control of plaque and gingivitis.", "Comparative effectiveness of an essential oil mouthrinse and dental floss in controlling interproximal gingivitis and plaque.", "Oral hygiene regimens, plaque control, and gingival health: a two-month clinical trial with antimicrobial agents.", "Use of dental floss. Effect on plaque and gingivitis.", "Mechanical devices versus antimicrobial rinses in plaque and gingivitis reduction." ]

[ "Manual floss is often difficult to use, particularly in hard to reach posterior teeth. Many prefer automated flossers because of their ease of use. The aim of the present study was to compare the effectiveness of an automated flosser to manual floss for anterior, premolar, and molar teeth using the plaque index (PI) and gingival (GI) index.\n A 10-week, two-treatment period, crossover design was used. The subjects were randomly assigned to control (C), manual (M), or automated (A) groups. The PI and GI were measured interdentally at baseline and days 15 and 30. Treatment subjects were assigned to the opposite group at the second baseline visit after a 2-week washout period. Subjects brushed twice a day. Treatment subjects used their respective floss once per day. Subjects refrained from oral hygiene 24 hours before study visits. The PI was measured pre- and postintervention on days 15 and 30. Mixed-effect analysis of covariance crossover models were used to test group effects at days 15 and 30 from both periods with the corresponding mean preintervention and baseline score as covariates for PI and GI, respectively. Within-subject treatment comparisons were made, and carryover effects were evaluated.\n The majority of subjects (N = 102) were students (mean age, 23.3 +/- 5.0 [SD] years) with minimal gingivitis at baseline. At days 15 and 30, the M group had more plaque than the A group for all regions (P < or = 0.008), and the C group had more plaque than the A (P <0.001) and M groups (P < or = 0.021) for all regions. No regional treatment effect was observed for the GI. Within-subject analyses were more favorable for the A group than the M group. No significant carryover effect was observed.\n The automated flossing device removed significantly more interproximal plaque in molar, premolar, and anterior teeth compared to manual floss at days 15 and 30. There was no significant difference in interdental inflammation between groups.", "The use of dental floss has long been considered to be effective in controlling interproximal plaque and gingivitis. The authors compared this method with that of use of a mouthrinse.\n Subjects with mild-to-moderate gingivitis enrolled in a long-term, six-month study. They received a dental prophylaxis and were randomized into one of the three following treatment groups: brushing and rinsing with an essential oil-containing mouthrinse (the BEO group), brushing and flossing (the BF group) and brushing and rinsing with a control rinse (the B group).\n A total of 326 subjects were evaluated. The BEO and BF had significantly lower (P < .001) mean interproximal Modified Gingival Index, or MGI, scores than did the B group at six months. The BEO group had lower mean interproximal Plaque Index, or PI, scores than the other two groups at both three and six months. The BF group's mean PI score was significantly lower than the B group's mean score at six months only. The magnitude of reductions for the BEO and the BF groups (vs. the B group) in MGI were 11.1 percent and 4.3 percent and for PI were 20.0 percent and 3.4 percent, respectively.\n In conjunction with professional care (prophylaxis) and toothbrushing over six months, rinsing twice daily with an essential oil-containing mouthrinse was at least as good as flossing daily in reducing interproximal plaque and gingivitis. Clinical Implications. When weighing recommendations for oral hygiene home care, clinicians should consider that an essential oil-containing mouthrinse may be a useful adjunct in patients with gingival inflammation.", "This single-blind, five parallel-arm, four-week randomized clinical trial was designed to compare the efficacy of a 0.05% cetylpyridinium chloride gel-releasing interdental brush (IDB) with standard interproximal cleaning devices for plaque and gingivitis reduction, and decreased frequency in interproximal gingival bleeding.\n After consenting, participants meeting inclusion criteria brushed their teeth, received a baseline examination and a professional cleaning, and were then block-randomized into five groups, with the plaque level serving as the blocking variable. All five groups performed standard tooth brushing as a background regimen. Three of the groups were respectively assigned to one of three interdental brush regimens, the fourth group was assigned to a standard flossing regimen (positive control), and the fifth group was assigned to a standard tooth brushing only regimen (control). Clinical outcome data were collected at two and four weeks.\n Of a total of 162 starting participants, 152 completed the study. There were no baseline differences among the five groups with respect to age, interproximal plaque score, interproximal gingivitis score, or percent of interproximal bleeding on probing. After two and four weeks, the 3 IDB groups exhibited 30-40 percent lower plaque levels than the control (p < 0.05). With respect to interproximal gingival scores, the active agent IDB group exhibited a statistically significant effect after two weeks, and all three IDB groups demonstrated significantly better outcomes after four weeks (p < 0.05). At two and four weeks, the three IDB groups demonstrated a greater reduction in interproximal bleeding points upon probing compared to the two control groups (p < 0.05). The group using the 0.05% cetylpyridinium gel-releasing IDB system did not demonstrate superior clinical results when compared to the two other IDB groups.\n When compared to control and positive control interdental cleaning procedures, daily use of IDBs was effective in reducing interproximal plaque and gingivitis scores, as well as interproximal bleeding on probing. The benefits were evident at two weeks, but were more consistent after four weeks. The 0.05% cetylpyridinium gel-releasing IDB system did not appear to confer a consistently independent incremental benefit.", "The objective of this study was to evaluate the effect of an oscillating/rotating/pulsating powered toothbrush on plaque and gingivitis prevention over a 9-month period.\n The study had an examiner-masked, randomized, three-group parallel design. A total of 122 subjects >or= 18 years of age in good general health and with at least five teeth per quadrant and no pockets >or= 5 mm were included. A 3-week preexperimental period of extensive oral home care, including rinses, was started to improve gingival health. Professional oral hygiene instruction with a manual brush was provided. At baseline, subjects were assigned to one of three regimens: twice daily brushing with a manual toothbrush, a manual toothbrush and the use of floss, or a powered toothbrush. Subjects were professionally instructed in their regimen and given a prophylaxis. Two weeks later, oral hygiene reinforcement was provided. Gingival bleeding, plaque, staining, and gingival abrasion were assessed during the preexperimental period and at baseline, 10 weeks, and 6 and 9 months.\n There was a significant reduction in plaque and gingivitis from the preexperimental period to baseline. At 10 weeks and 6 and 9 months, the level of plaque was statistically significantly lower with the powered toothbrush versus the other two regimens (P <or= 0.002). At 10 weeks and 6 months, the level of bleeding in the powered toothbrush group was statistically significantly lower versus manual brushing alone (P <or= 0.024).\n The powered toothbrush maintained lower plaque levels for 9 months following the 3-week treatment phase better than the manual toothbrush with or without floss. The powered toothbrush showed significant benefits in preventing gingival bleeding versus manual brushing alone. All regimens were safe for oral tissues.", "Dental floss is only used by a small part of the population on a daily basis. Therefore, an easy, applicable alternative is needed. This alternative could be a mouthrinse with antimicrobial activity for daily use. The aim of the present study was to evaluate the efficacy of two mouthrinses in reducing interdental plaque and gingivitis compared to dental floss.\n A total of 156 healthy volunteers were randomly assigned to the following groups: 1) toothbrushing and rinsing (0.06% chlorhexidine and 0.025% fluoride); 2) toothbrushing and rinsing (0.1% cetylpyridiniumchloride and 0.025% fluoride); 3) toothbrushing and flossing; and 4) toothbrushing only (N = 39 subjects in each group). At baseline, the modified proximal plaque index (MPPI) and papillary bleeding index (PBI) were recorded. Thereafter, subjects had to brush in the usual manner during 8 weeks. Additionally, test groups had to rinse once a day (groups 1 and 2: 30 seconds) or to floss (group 3). Eight weeks after baseline, indices were recorded again and improvements were calculated. Analysis of variance (ANOVA) and the Bonferroni test served for statistical analysis.\n After 8 weeks, reductions for all indices were found in all groups (P <0.05). With respect to the MPPI, mouthrinse groups performed better than the control and floss groups: 1) 0.73; 2) 0.82; 3) 0.40; and 4) 0.32 (P <0.05). The PBI showed no statistically significant difference between groups: 1) 0.46; 2); 0.50; 3); 0.42; and 4) 0.37.\n The results suggest that, in combination with toothbrushing, daily use of the tested mouthrinses may result in a higher interproximal plaque reduction than daily flossing.", "nan", "This study consisted of 24 dental students, who 10 days prior to the start of the experimental period, were thoroughly scaled and given instructions in the use of a rubber tip stimulator, unwaxed dental floss, and a modified Bass brushing technique. On day 0, the subjects had reached a high level of interproximal gingival health as measured by intracrevicular exudate flow and löe's Gingival Index. Subjects were then randomly divided into 4 groups which were to brush; brush and floss; brush and rubber tip; and brush, floss and rubber tip. Evaluation was performed on days 0, 9, 15, and 33 using Löe's Gingival Index, Podchadley's Plaque Index, and gingival exudate flow. The results of this study indicate that interproximal gingival health can be maintained in motivated patients with initially healthy gingivae (for at least several weeks) with proper use of the modified Bass brushing technique alone.", "The objective of this examiner-blind clinical study was to investigate the efficacy of three oral hygiene regimens for the control of gingivitis and supragingival plaque.\n Following a baseline examination for gingivitis and supragingival plaque, qualifying adult male and female subjects from the San Francisco, California area were stratified into three treatment groups, which were balanced for plaque. The groups were then randomly assigned to one of three oral hygiene regimens: 1) twice-daily tooth brushing with Colgate Total Toothpaste, accompanied by once-daily flossing after brushing; 2) twice-daily tooth brushing with Colgate Total Toothpaste without flossing; and 3) twice-daily tooth brushing with a sodium fluoride toothpaste, accompanied by once-daily flossing after brushing. All subjects were given a complete oral prophylaxis, and dispensed their assigned treatment product(s), along with a soft-bristled adult toothbrush for home use. All dentifrice products were supplied in the original packaging to which overwrapping had been applied. Subjects were instructed to brush their teeth for one minute twice daily (morning and evening) using only the dentifrice provided, and to refrain from using anything other than their assigned oral hygiene products for the duration of the study. In addition, subjects were instructed to refrain from any routine dental treatment (except emergency) during the course of the study. There were no restrictions regarding diet or smoking habits over the course of the study. Examinations for gingivitis and supragingival plaque, and oral soft tissue assessments were repeated after three months, and again after six months of product use.\n One-hundred fourteen (114) subjects complied with the protocol and completed the six-month examinations. Statistical analyses showed similar results for both whole-mouth and interproximal scoring sites after six months of product use. Although not statistically significant, subjects using Colgate Total Toothpaste accompanied by the use of dental floss had numerically lower six-month scores for gingivitis and supragingival plaque formation when compared to the scores of subjects using Colgate Total Toothpaste without the use of dental floss. Relative to the sodium fluoride toothpaste accompanied by the use of dental floss, subjects using Colgate Total Toothpaste, both with and without the use of dental floss, exhibited statistically significant reductions in gingivitis and supragingival plaque formation after six months of product use.\n The results of this clinical study support the conclusion that the use of Colgate Total Toothpaste, both with and without the use of dental floss, provided statistically significant improvements over the sodium fluoride toothpaste plus flossing regimen with respect to the control of gingivitis and supragingival plaque formation. Although not statistically significant, numerically lower six-month scores for gingivitis and supragingival plaque were associated with Colgate Total Toothpaste accompanied by the use of dental floss, when compared with Colgate Total Toothpaste without the use of dental floss.", "To compare the effectiveness of rinsing with an essential oil-containing antimicrobial mouthrinse with that of dental floss in reducing interproximal gingivitis and plaque in an unsupervised 6-month clinical trial designed in accordance with ADA Acceptance Program Guidelines.\n 319 qualifying subjects, aged 18-63, were randomized into one of three groups: essential oil mouthrinse (Listerine Antiseptic); dental floss (Reach Dental Floss); or a negative control rinse. At baseline, subjects received a complete oral soft tissue examination and scoring of the Modified Gingival Index (MGI), modified Quigley-Hein Plaque Index (PI), and bleeding index (BI). Following a complete dental prophylaxis and receiving flossing or rinsing instructions, subjects started on their respective regimen. They continued on their assigned regimen unsupervised at home, in addition to toothbrushing, and were reexamined at 3 and 6 months. The treatment groups were compared with respect to baseline demographic and clinical variables. The primary efficacy variables were mean interproximal MGI and PI at 6 months. Intergroup differences at 3 and 6 months were tested using a one-way analysis of covariance model with treatment as a factor and the respective baseline value as the covariate. In addition, the essential oil mouthrinse was compared to floss for interproximal gingivitis reduction using \"at least as good as\" statistical criteria.\n 301 subjects were considered evaluable. There were no statistically significant differences among the 3 groups at baseline, with the exception of the essential oil mouthrinse group having significantly fewer AfroAmerican subjects than the other two groups. For the interproximal MGI, the essential oil mouthrinse and flossing were both significantly more effective than the negative control (P < 0.001) at 3 and 6 months. The essential oil mouthrinse was shown to be \"at least as good as\" dental floss for the control of interproximal gingivitis. For the interproximal PI, the essential oil mouthrinse was significantly more effective than the negative control at 3 and 6 months (P < 0.001) while flossing was significantly more effective than the negative control at 3 months (P < 0.05) but not at 6 months. The essential oil mouthrinse was significantly more effective than floss (P < 0.001) at both these time periods.", "The purpose of this study was to examine the effects of various product combinations involving brush, paste, rinse, and floss on the prevention of plaque regrowth and gingivitis.\n In this randomized, parallel-group, examiner-blind, eight-week study, 179 subjects with gingivitis had a dental prophylaxis and were randomly assigned to one of six product combinations: 1) Colgate Wave manual toothbrush + Colgate Total dentifrice (0.3% triclosan/copolymer dentifrice); 2) Wave + Total + Listerine (essential oils rinse); 3) Oral-B CrossAction manual toothbrush + Crest Pro-Health dentifrice (0.454% stannous fluoride/sodium hexametaphosphate); 4) CrossAction + Pro-Health dentifrice + Crest Pro-Health Rinse (0.07% cetylpyridinium chloride rinse); 5) Oral-B ProfessionalCare Series 8000 power toothbrush + Pro-Health dentifrice; or 6) ProfessionalCare power brush + Pro-Health dentifrice + Oral-B Hummingbird power flosser. Subjects used their test products for the duration of the study. Whole mouth plaque, gingivitis, and product-related adverse events were assessed. Treatments were compared at a 0.05 level of significance.\n One-hundred and seventy-four subjects completed the study and were included in the data analysis. At Week 8, the overnight adjusted whole mouth plaque scores were statistically significantly lower in all other groups relative to the Wave + Total group (p < or = 0.030). Plaque scores were also statistically significantly lower (approximately 20%) in both groups where a therapeutic rinse was added to a manual brush and therapeutic paste relative to scores for the brush plus paste without a rinse (p < or = 0.034). All groups showed a reduction in gingivitis at Week 4, and mean scores remained stable or increased slightly at Week 8. The power toothbrush groups were directionally better at preventing gingivitis than the manual groups at Weeks 4 and 8.\n Reductions in overnight plaque were seen when therapeutic rinses were added to manual brush plus therapeutic dentifrice regimens above that observed with a manual brush and therapeutic dentifrice alone.", "nan", "The effectiveness of mechanical oral cleaning and oral antimicrobial rinses was compared for gingivitis and bacterial plaque control in 158 subjects. Teeth were brushed ad lib throughout; four of the five groups used either an interdental cleaner, dental floss, an essential oil mouthwash or a cetypyridinium mouthwash. Gingival bleeding (EIBI), visual inflammation (VGI), and tooth plaque coverage were evaluated at zero, six and 12 weeks of product use. After six weeks, bleeding reduction was 42% greater for the interdental cleaner and 21% greater for the dental floss than for the control. All groups showed a further decrease after 12 weeks, but only the 49% reduction of the interdental cleaner was significantly greater than the control. The rinses showed no more reduction in bleeding sites than the control throughout the study. VGI scores were no different from the control for any of the groups. However, the EIBI proved much more sensitive than the visual method finding three times as many inflamed sites. Plaque was reduced by both antimicrobial rinses 27% more than the control over 12 weeks; the interdental cleaner and dental floss groups showed no significant incremental plaque reductions. The results suggest antimicrobial rinses reduce plaque on visible tooth surfaces, but do not penetrate sufficiently between teeth to affect interdental plaque and thus interdental inflammation. However, by disturbing interdental plaque, both dental floss and the interdental cleaner have little effect on visible tooth surface plaque accumulation, yet produce a significant reduction in gingival inflammation." ]

[ "9212042", "11076326", "8970936", "14630985" ]

[ "L-thyroxine treatment of preterm newborns: clinical and endocrine effects.", "Postnatal thyroxine supplementation in infants less than 32 weeks' gestation: effects on pulmonary morbidity.", "Effects of thyroxine supplementation on neurologic development in infants born at less than 30 weeks' gestation.", "A randomized, masked study of triiodothyronine plus thyroxine administration in preterm infants less than 28 weeks of gestational age: hormonal and clinical effects." ]

[ "Preterm newborns have low serum thyroxine (T4) levels compared with late-gestational fetuses. Low thyroid hormone levels are associated with increased severity of neonatal illness and neurodevelopmental dysfunction. We assessed the endocrine and clinical effects of increasing serum T4 levels in preterm newborns with a gestational age <31 wk. Forty newborns were randomized in a double blind protocol: 20 infants received a daily dose of 20 microg/kg L-T4 for 2 wk, whereas 20 control infants received saline. Serum concentrations of T4, triiodothyronine (T3), reverse T3 (rT3), thyroglobulin (TG), and TSH were measured weekly as well as serum levels of GH, prolactin, and IGF-I. After 2 wk, a TSH-releasing hormone (TRH) test was performed. Neonatal illness and outcome was evaluated by noting heart rate, oxygen requirement, duration of ventilation, development of chronic lung disease, oral fluid intake, and weight gain; a Bayley score was done at the corrected age of 7 mo. L-T4 administration induced a marked increase in serum T4 without apparent change in T3 levels, whereas the postnatal decline in serum rT3 was more gradual. L-T4 treatment was associated with a decrease in serum TG and TSH levels. TRH injection induced a definite rise in serum TSH and T3 in controls, but not in L-T4 treated newborns. Neither L-T4 treatment, nor TRH administration appeared to alter circulating levels of prolactin, GH, or IGF-I. In contrast to the pronounced endocrine effects, no clinical effects of L-T4 administration were detected.", "Transient hypothyroxinemia in premature newborns has been linked with poor neonatal outcomes. We designed this study to evaluate the effects of early thyroxine (T4) administration in the premature infant.\n A total of 49 newborns less than 32 weeks' gestation, were randomized in a double-blind, placebo-controlled trial. Within the first 48 hours of life, T4 (10 or 20 micrograms/kg; intravenous or through nasogastric tube, respectively) was administered for a total of 21 days. Chronic lung disease, the primary outcome variable, was defined by oxygen dependency at 28 days of life.\n The incidence of chronic lung disease, death, grade III or IV intraventricular hemorrhage, periventricular leukomalacia, and sepsis was not different in the placebo and treated groups.\n Early T4 supplementation in preterm newborns less than 32 weeks' gestation does not decrease the incidence of chronic lung disease or other complications of prematurity.", "Premature infants who have transient hypothyroxinemia in the first weeks of life may have developmental delay and neurologic dysfunction. Whether thyroxine treatment during this period results in improved developmental outcomes is not known.\n We carried out a randomized, placebo-controlled, double-blind trial of thyroxine supplementation in 200 infants born at less than 30 weeks' gestation. Thyroxine (8 microg per kilogram of birth weight) or placebo was administered daily, starting 12 to 24 hours after birth, for six weeks. Plasma free thyroxine concentrations were measured weekly for the first eight weeks after birth. Scores on the Bayley Mental and Psychomotor Development Indexes and neurologic function were assessed at 6, 12, and 24 months of age (corrected for prematurity).\n Mortality and morbidity up to the time of discharge from the hospital were similar in the study groups. At 24 months of age, 157 infants were evaluated. Overall, neither mental nor psychomotor scores differed significantly between the study groups at any time, nor was the frequency of abnormal neurologic outcome significantly different. In thyroxine-treated infants born at gestational ages of less than 27 weeks, the score on the Bayley Mental Development Index at 24 months of age was 18 points higher than the score for the infants with similar gestational ages at birth in the placebo group (P=0.01); for thyroxine-treated infants born at 27 weeks or later, the mental-development score was 10 points lower than that of their counterparts in the placebo group (P=0.03). There was no relation between the initial plasma free thyroxine concentration and the effect of treatment.\n In infants born before 30 weeks' gestation, thyroxine supplementation does not improve the developmental outcome at 24 months.", "A randomized, placebo-controlled, masked study was conducted of the responses of thyroid parameters, cortisol, and the cardiovascular system to a single dose of triiodothyronine (T(3)) 24 h after birth, followed by a daily dose of thyroxine (T(4)) during 6 wk to infants <28 wk gestational age. Thirty-one infants were assigned to three groups: 1) group A: T(3) 24 h after birth plus daily T(4) during 6 wk; 2) group B: placebo T(3) and T(4) during 6 wk; and 3) group C: placebo T(3) and placebo T(4). T(4), free T(4), T(3), free T(3), reverse T(3), thyroid-stimulating hormone, and cortisol were measured in cord blood and on days 1, 3, 7, 14, 21, 42, and 56. Data on pulse rate, blood pressure, and cumulative dose of inotropic agents were collected. T(3) (0.5 microg/kg) resulted in a plasma increase until day 3. Thereafter, plasma T(3) levels were comparable between the groups. T(4), free T(4), and reverse T(3) were increased in groups A and B during the period of T(4) administration. Thyroid-stimulating hormone suppression was of shorter duration in group A. T(3) and T(4) administration did not have any effect on cortisol levels. We did not find any effects of T(3) or of T(4) administration on the cardiovascular system. A single injection of T(3) (0.5 microg/kg) given 22-26 h after birth only leads to a 2-d increase of T(3) levels and does not have effects on the cardiovascular system. This study does not support the use of T(3) according to our regimen in preterm infants." ]

[ "9532318", "1642520", "11059522", "12554890", "9887897" ]

[ "Clinical study of yoga techniques in university students with asthma: a controlled study.", "Deep diaphragmatic breathing: rehabilitation exercises for the asthmatic patient.", "A clinical trial of the Buteyko Breathing Technique in asthma as taught by a video.", "Breathing retraining for dysfunctional breathing in asthma: a randomised controlled trial.", "Buteyko breathing techniques in asthma: a blinded randomised controlled trial." ]

[ "Adult asthmatics, ranging from 19 to 52 years from an asthma and allergy clinic in a university setting volunteered to participate in the study. The 17 students were randomly divided into yoga (9 subjects) and nonyoga control (8 subjects) groups. The yoga group was taught a set of breathing and relaxation techniques including breath slowing exercises (pranayama), physical postures (yogasanas), and meditation. Yoga techniques were taught at the university health center, three times a week for 16 weeks. All the subjects in both groups maintained daily symptom and medication diaries, collected A.M. and P.M. peak flow readings, and completed weekly questionnaires. Spirometry was performed on each subject every week. Analysis of the data showed that the subjects in the yoga group reported a significant degree of relaxation, positive attitude, and better yoga exercise tolerance. There was also a tendency toward lesser usage of beta adrenergic inhalers. The pulmonary functions did not vary significantly between yoga and control groups. Yoga techniques seem beneficial as an adjunct to the medical management of asthma.", "A new diaphragmatic breathing technique practiced without the aid of a physical corset is outlined, and the findings from a study of its application in the respiratory rehabilitation of asthmatic patients are presented. Sixty-seven asthmatic adults randomly assigned to either deep diaphragmatic breathing training, physical exercise training, or a waiting list control group participated in a 16-week program. Deep diaphragmatic training resulted in significant reductions in medication use and in the intensity of asthmatic symptoms. Importantly, a nearly 300% increase in time spent in physical activities also resulted from deep diaphragmatic training. A follow-up at two months found many patients had returned to earlier medication levels and sedentary habits. A strengthened musculature can replace the need for a physical aid in this respiratory habilitation; adherence to its use may require individually-tailored encouragement.", "The Buteyko Breathing Technique (BBT) is promoted as a drug-free asthma therapy. It is based on the premise that raising blood PaCO2 through hypoventilation can treat asthma. Our study was designed to examine whether the Buteyko Breathing Technique, as taught by a video, is an efficacious asthma therapy. Thirty-six adult subjects with mild to moderate asthma were randomized to receive either a BBT or placebo video to watch at home twice per day for 4 weeks. Asthma-related quality of life, peak expiratory flow (PEF), symptoms, and asthma medication intake were assessed both before and after intervention. Our results demonstrated a significant improvement in quality of life among those assigned to the BBT compared with placebo (p = 0.043), as well as a significant reduction in inhaled bronchodilator intake (p = 0.008). We conclude that the BBT may be effective in improving the quality of life and reducing the intake of inhaled reliever medication in patients with asthma. These results warrant further investigation.", "Functional breathing disorders may complicate asthma and impair quality of life. This study aimed to determine the effectiveness of physiotherapy based breathing retraining for patients treated for asthma in the community who have symptoms suggestive of dysfunctional breathing.\n 33 adult patients aged 17-65 with diagnosed and currently treated asthma and Nijmegen questionnaire scores > or =23 were recruited to a randomised controlled trial comparing short physiotherapy breathing retraining and an asthma nurse education control. The main outcome measures were asthma specific health status (Asthma Quality of Life questionnaire) and Nijmegen questionnaire scores\n Of the 33 who entered the study, data were available on 31 after 1 month and 28 at 6 months. The median (interquartile range) changes in overall asthma quality of life score at 1 month were 0.6 (0.05-1.12) and 0.09 (-0.25-0.26) for the breathing retraining and education groups, respectively (p=0.018), 0.42 (0.11-1.17) and 0.09 (-0.58-0.5) for the symptoms domain (p=0.042), 0.52 (0.09-1.25) and 0 (-0.45-0.45) for the activities domain (p=0.007), and 0.50 (0-1.50) and -0.25 (-0.75-0.75) for the environment domain (p=0.018). Only the change in the activities domain remained significant at 6 months (0.83 (-0.10-1.71) and -0.05 (-0.74-0.34), p=0.018), although trends to improvement were seen in the overall score (p=0.065), the symptoms domain (p=0.059), and the environment domain (p=0.065). There was a correlation between changes in quality of life scores and Nijmegen questionnaire scores at 1 month and at 6 months. The number needed to treat to produce a clinically important improvement in health status was 1.96 and 3.57 at 1 and 6 months.\n Over half the patients treated for asthma in the community who have symptoms suggestive of dysfunctional breathing show a clinically relevant improvement in quality of life following a brief physiotherapy intervention. This improvement is maintained in over 25% 6 months after the intervention.", "To evaluate the effect of Buteyko breathing techniques (BBT) in the management of asthma.\n Prospective, blinded, randomised study comparing the effect of BBT with control classes in 39 subjects with asthma. The study was conducted from January 1995 to April 1995.\n Subjects recruited from the community, aged 12 to 70 years, with asthma and substantial medication use.\n Medication use; morning peak expiratory flow (PEF); forced expiratory volume in one second (FEV1); end-tidal (ET) CO2; resting minute volume (MV); and quality of life (QOL) score, measured at three months.\n No change in daily PEF or FEV1 was noted in either group. At three months, the BBT group had a median reduction in daily beta 2-agonist dose of 904 micrograms (range, 29 micrograms to 3129 micrograms), whereas the control group had a median reduction of 57 micrograms (range, -2343 micrograms to 1143 micrograms) (P = 0.002). Daily inhaled steroid dose fell 49% (range, -100% to 150%) for the BBT group and 0 (range, -82% to +100%) for the control group (P = 0.06). A trend towards greater improvement in QOL score was noted for BBT subjects (P = 0.09). Initial MV was high and similar in both groups; by three months, MV was lower in the BBT group than in the control group (P = 0.004). ET CO2 was low in both groups and did not change with treatment.\n Those practising BBT reduced hyperventilation and their use of beta 2-agonists. A trend toward reduced inhaled steroid use and better quality of life was observed in these patients without objective changes in measures of airway calibre." ]

[ "9661546", "2036187", "15313860", "8895262", "8894809", "11956540", "12670818", "7598849", "8233511", "15573192", "8630203", "16983840", "11226091", "15979735", "10520389" ]

[ "The effect of preoperative dexamethasone on the immediate and delayed postoperative morbidity in children undergoing adenotonsillectomy.", "The effect of steroid therapy on recovery from tonsillectomy in children.", "Perioperative steroids in tonsillectomy using electrocautery and sharp dissection techniques.", "Dexamethasone decreases vomiting by children after tonsillectomy.", "Dexamethasone in adenotonsillectomy.", "Does dexamethasone with preemptive analgesia improve pediatric tonsillectomy pain?", "Dexamethasone reduces postoperative vomiting and pain after pediatric tonsillectomy.", "Use of intraoperative corticosteroids in pediatric tonsillectomy.", "The effects of preoperative steroids on tonsillectomy patients.", "Use of dexamethasone to reduce postoperative vomiting and pain after pediatric tonsillectomy procedures.", "The effect of intravenous dexamethasone in pediatric adenotonsillectomy.", "[The effect of steroid therapy on post adenotonsillectomy recovery].", "The effect of dexamethasone on postoperative vomiting after tonsillectomy.", "The effect of preoperative dexamethasone on early oral intake, vomiting and pain after tonsillectomy.", "The effect of single dose intravenous dexamethasone in tonsillectomy in children." ]

[ "In this prospective, randomized, double-blind, placebo-controlled study, we examined the effect of preoperative dexamethasone on postoperative nausea and vomiting (PONV) and 24-h recovery in children undergoing tonsillectomy. One hundred thirty children, 2-12 yr of age, ASA physical status I or II, completed the study. All children received oral midazolam 0.5-0.6 mg/kg preoperatively. Anesthesia was induced with halothane and nitrous oxide in 60% oxygen and maintained with nitrous oxide and isoflurane. Intubation was facilitated by mivacurium 0.2 mg/kg. Each child received fentanyl 1 microgram/kg i.v. before initiation of surgery, as well as dexamethasone 1 mg/kg (maximal dose 25 mg) (steroid group) or an equal volume of saline (control group). Intraoperative fluids were standardized to 25-30 mL/kg lactated Ringer's solution. All tonsillectomies were performed under the supervision of one attending surgeon using an electrodissection technique. Postoperatively, fentanyl and acetaminophen with codeine elixir were administered as needed for pain. Rescue antiemetics were administered when a child experienced two episodes of retching and/or vomiting. Before home discharge, the incidence of PONV, need for rescue antiemetics, quality or oral intake, and analgesic requirements did not differ between groups. However, during the 24 h after discharge, more patients in the control group experienced PONV (62% vs 24% in the steroid group) and complained of poor oral intake. Additionally, more children in the control group (8% vs 0% in the steroid group) returned to the hospital for the management of PONV and/or poor oral intake. The preoperative administration of dexamethasone significantly decreased the incidence of PONV over the 24 h after home discharge in these children. Implications: In this double blind, placebo-controlled study, we examined the efficacy of a single large dose (1 mg/kg; maximal dose 25 mg) of preoperative dexamethasone on posttonsillectomy postoperative nausea and vomiting (PONV) in children 2-12 yr of age undergoing tonsillectomy. Compared with placebo, dexamethasone significantly decreased the incidence of PONV in the 24 h after discharge, improved oral intake, decreased the frequency of parental phone calls, and resulted in no hospital returns for the management of PONV and/or poor oral intake.", "A prospective, randomized, double-blind study to determine the postoperative effects of steroids in tonsillectomy was performed on 25 children from 4 to 12 years of age. A single intravenous dose of dexamethasone or a placebo was administered at onset of surgery. Other preoperative and postoperative medications, including antibiotics, anesthesia, and surgical techniques were standardized as noted in this article. The ability to return to a full or semifull diet occurred on the third and fourth postoperative days, significantly sooner in the steroid-treated patients than in the control patients. By the fifth and sixth days, the control group were eating as well as those children who received steroids. No significant differences were observed in postoperative pain, nausea, emesis, fever, or in the need for postoperative pain medications. This preliminary article concludes that a single preoperative dose of steroid results in an earlier return to a normal (full) diet in children who had undergone tonsillectomy.", "To determine the effect of preoperative dexamethasone sodium phosphate administration on posttonsillectomy morbidity for electrocautery (\"hot\") and sharp (\"cold\") dissection techniques.\n Prospective, randomized, double-blind study.\n University pediatric hospital and county teaching hospital. Subjects A total of 219 children, aged 9 months to 12 years, undergoing tonsillectomy. Intervention Participants who underwent tonsillectomy were randomly assigned to receive either intravenous dexamethasone sodium phosphate (1 mg/kg) or placebo.\n Pain scores, oral intake, and emesis on postoperative day (POD) 1.\n A total of 106 subjects (62 undergoing hot and 44 cold tonsillectomies) received preoperative steroids, and 113 (56 hot and 57 cold tonsillectomies) received placebo. On POD 1, pain scores reported by patients (P =.02), parents (P =.002), and physicians (P<.001) were significantly lower in subjects receiving steroids than in those receiving placebo. Emesis was reduced from a mean of 2.1 (placebo group) to 1.2 episodes (steroid group) (P =.02). Oral intake improved from 24.5% of normal diet (placebo) to 31.7% (steroid group) (P =.004). When all 4 groups were compared (cold placebo, cold steroid, hot placebo, and hot steroid), pain scores reported by physicians and parents were significantly lower in the cold steroid group than in the other groups.\n Perioperative dexamethasone use reduces posttonsillectomy morbidity in pediatric patients in the early postoperative period after hot or cold tonsillectomy. The combination of steroid and cold dissection technique provided the greatest advantage in reducing posttonsillectomy subjective pain levels.", "We evaluated the effect of dexamethasone on vomiting after elective tonsillectomy in 133 healthy children aged 2-12 yr in a randomized, stratified, blocked, double-blind, placebo-controlled study. General anesthesia was induced by inhalation of N2O and halothane or intravenously (IV) with propofol. Anesthesia was maintained with N2O and halothane. Dexamethasone 150 micrograms/kg up to a maximum dose of 8 mg, or placebo, was administered IV before surgery. All patients received 1.5 mg/kg codeine intramuscularly (IM) intraoperatively. Perioperative IV fluids, management of emesis, postoperative pain and hospital discharge criteria were all standardized. The groups were similar with respect to number, age, weight, length of surgery, and estimated intraoperative blood loss. Dexamethasone reduced the overall incidence of vomiting from 72% (placebo) to 40% (P < 0.001). Vomiting, both in-hospital and postdischarge, was decreased by the prophylactic administration of dexamethasone. Each episode of in-hospital vomiting prolonged discharge by 13 +/- 2 min, mean +/- SD (P < 0.001). In conclusion, dexamethasone markedly decreased vomiting by healthy children after elective tonsillectomy in an ambulatory hospital setting.", "Edema contributes substantially to the postoperative discomfort and morbidity of adenotonsillectomy. In a double-blind study, 58 children undergoing adenotonsillectomy were given a single intraoperative dose of either dexamethasone or saline. The steroid markedly affected the postoperative course in the first day after surgery. According to parental reports, the percentage of patients vomiting was reduced from 48 to 4%. Severe throat pain was reported in 57% of controls and only 20% of dexamethasone patients. Twice as many steroid patients as controls tolerated some soft food on the first postoperative day. It appears that dexamethasone can greatly improve patient diet and comfort after adenotonsillectomy.", "The study goal was to determine whether the combination of dexamethasone with preemptive analgesia has an additive effect in further improving recovery.\n We conducted a prospective, randomized, double-blinded trial of 50 children undergoing tonsillectomy at a university ambulatory surgery center. One study group received 1 intravenous dose of dexamethasone, and another group received 1 dose of saline solution. All patients received tonsillar fossa injections of ropivacaine plus clonidine before tonsil excision.\n The 2 study groups were similar in main outcome measurements. Pain intensity and quality of life were not statistically different between the groups. There was a small trend to less trismus and less cumulative codeine use in the steroid group. Overall, there was a very low incidence of nausea and vomiting in both groups, which may have been due to the preemptive analgesia.\n Dexamethasone does not significantly improve the morbidity of pediatric tonsillectomy when preemptive analgesia with ropivacaine and clonidine is used concurrently.", "Previous studies on dexamethasone's antiemetic and analgesic potential in children undergoing tonsillectomy have produced conflicting results. The aim of this study was to evaluate the effects of a single dose of dexamethasone on the incidence and severity of postoperative vomiting and pain in children undergoing electrocautery tonsillectomy under standardized general anesthesia.\n In a double-blinded study, 120 patients were randomly allocated to receive either dexamethasone 0.5 mg.kg(-1) (maximum dose 8 mg) iv or an equivalent volume of saline preoperatively. The incidence of early and late vomiting, need for rescue antiemetics, time to first oral intake, time to first demand of analgesia and analgesic consumption were compared in both groups. Pain scores used included Children's Hospital Eastern Ontario Pain Scale, \"faces\", and a 0-10 visual analogue pain scale.\n Compared with placebo, dexamethasone significantly decreased the incidence of early and late vomiting (P < 0.05, P < 0.001 respectively). Fewer patients in the dexamethasone group needed antiemetic rescue (P < 0.01). The time to first oral intake was shorter, and the time to first dose of analgesic was longer in the dexamethasone group (P < 0.01). Pain scores 30 min after extubation were lower (P < 0.05) in the dexamethasone group. At 12 and 24 hr postoperative swallowing was still significantly less painful in the dexamethasone group than in the control group (P < 0.01).\n Preoperative dexamethasone 0.5 mg.kg(-1) iv reduced both postoperative vomiting and pain in children after electrocautery tonsillectomy.", "To determine the effects of a single dose of dexamethasone sodium phosphate on postoperative morbidity in children undergoing tonsillectomy.\n Randomized, double-blind, placebo-control clinical trial.\n Academic, tertiary care children's hospital.\n Sixty-nine children (35 boys, 34 girls), aged 3 to 18 years, undergoing tonsillectomy with or without adenoidectomy.\n Patients were randomized to receive a single dose of intravenous dexamethasone or saline.\n Pain scores, determined by a Faces Scale, were obtained at 4-hour intervals during the first postoperative day and daily for 7 days thereafter. Total use of an analgesic; type of diet; level of activity; presence of halitosis, nausea, emesis, or fever; and incidence of postoperative bleeding were also compared between the two groups.\n The two groups of children were similar in age, gender, diagnosis, and surgical time. Pain scores in the postoperative period were identical while the patients were in the hospital and for the first 7 days after discharge. No statistically significant differences were noted in pain scores, nausea, emesis, halitosis, analgesic medications required, diet, or activity levels between the two groups of patients.\n A single intraoperative dose of dexamethasone did not appreciably affect postoperative morbidity in children undergoing tonsillectomy.", "A prospective, randomized, double-blind study to determine the postoperative efficacy of steroids in tonsillectomy was performed in 49 children. A single dose of intravenous dexamethasone or placebo was administered after each child was anesthetized. Postoperatively each child was examined for objective signs of trismus (measured by interincisor distance), temperature elevation, and weight loss, as well as for subjective signs of mouth odor, oral intake, pain, level of activity, and analgesic usage. There were no statistical differences noted in any of the variables compared in the two groups and the complication rates were also similar.", "The purpose of this study is to determine whether a single dose of dexamethasone 0.5mg/kg administered before surgery could decrease post operative vomiting and pain and improves oral intake in the first 24-hours after pediatric tonsillectomy procedures.\n It is a randomized, double blind, placebo controlled study. Sixty children age 2-12-years ASA 1 and 11 were scheduled for tonsillectomy, dexamethasone (n=29) and control group (n=31) were enrolled in the study. Dexamethasone group received 0.5mg/kg intravenous dexamethasone and control group received saline at the time of induction. The anesthetic regimen and surgical procedures were standardized for all patients. All patients were observed in post anesthesia care unit (PACU) and ward for post operative vomiting, pain, need for rescue antiemetic or analgesia and time for first oral intake for 24-hours.\n Data from 60 patients were analyzed. The overall incidence of early as well as late vomiting was significantly less in dexamethasone as compared to control group (37% versus 74% P=0.016), overall incidence of retching was 29% in control and 3.4% in dexamethasone (p=0.008). Vomiting once or more than once was significantly high in control as compared to dexamethasone group. The need for rescue antiemetic, the time to first oral intake and analgesic requirements did not show any significant difference in both groups.\n Dexamethasone is considered safe and there was no adverse effects associated with a single dose of dexamethasone. Although the need for rescue antiemetic, time to oral intake and analgesia requirements in both groups were not significant, however, we found that dexamethasone does have antiemetic properties as overall incidence of retching and vomiting was significantly less in dexamethasone group as compared to control group in children who underwent tonsillectomy.", "To determine whether the intravenous administration of dexamethasone sodium phosphate before tonsillectomy and adenoidectomy can reduce the morbidity from, and increase the safety of, this procedure.\n Prospective, randomized, double-blind, placebo-controlled clinical trial.\n A university medical center, caring for both ambulatory and hospitalized children.\n Eighty children aged 3 to 15 years undergoing tonsillectomy and adenoidectomy for either chronic tonsillitis or adenotonsillar hypertrophy (obstructive sleep apnea and/or upper airway obstruction).\n Forty-one children received intravenous dexamethasone sodium phosphate (1 mg/kg up to 16 mg) and 39 received placebo before undergoing an electrocautery dissection tonsillectomy and adenoidectomy.\n Postoperative oral intake, pain, vomiting, temperature, and complications.\n Patients who received intravenous dexamethasone had significantly less trismus, vomiting, and elevations of temperature 6 hours after surgery and more oral intake (liquids and soft solids) at 24 hours. Three children, all of whom were in the placebo group, had emergency department visits for pain and dehydration. Each group had one child who had a secondary hemorrhage (no surgery needed), one child who had pneumonia, and one child who had night terrors.\n Treatment with intravenous dexamethasone before electrocautery tonsillectomy and adenoidectomy is safe, increases early postoperative oral intake, and decreases morbidity.", "Previous studies on dexamethasone's antiemetic and antinflammatory potential in patients undergoing adenotonsillectomy have produced conflicting results.\n To determine the effect of intraoperative I.V. single dose dexamethasone on recovery and complications after adenotonsillitis while anesthesia techniques, surgical techniques and perioperative treatment are standardized.\n Prospective randomized, controlled study.\n A total of 230 patients aged 2-16 years undergoing elective adenotonsillectomy enrolled in the study. Patients were randomly assigned to receive i.v. dexamethasone 0.5 mg/kg (study group), or no treatment (control group). Pain score, emesis, oral intake and bleeding were assessed on the first and tenth postoperative day.\n Overall, 204 completed the study, 101 in the study group, 103 in the control group. It was found that intraoperative single I.V. dexamethasone significantly reduces emesis during the first postoperative day (P < 0.0001), significantly reduces pain score on the first (P < 0.0001), and tenth postoperative day (P = 0.053), significantly increases the number of patients returning to soft diet on the first postoperative day (P = 0.0002) and normal diet on the tenth postoperative day (P < 0.0001). No significant difference in bleeding tendency between the two groups was noted (P = 0.7202).\n Intraoperative injection of I.V. dexamethasone 0.5 mg/kg effectively reduced post adenotonsillectomy morbidity.", "In this double-blinded, randomized, placebo-controlled study, we assessed the effect of dexamethasone 0.5 mg/kg IV administered preoperatively in 110 children 2-12 yr old, undergoing electrodissection adenotonsillectomy, using a standardized anesthetic technique. The incidence of early and late vomiting, the time to first oral intake, the quality of oral intake, the satisfaction scores, and the duration of IV hydration were compared in both groups. The overall incidence of vomiting, as well as the incidence of late vomiting, was significantly less in the Dexamethasone group as compared with the Saline group (23% and 19% vs 51% and 34%, respectively). The time to first oral intake and the duration of IV hydration were shorter in the Dexamethasone group compared with the Saline group (P < 0.05). The quality of oral intake and the satisfaction scores were better in the Dexamethasone group than in the Saline group (P < 0.05). This report confirms the beneficial effect of IV dexamethasone on both vomiting and oral intake in children undergoing electrodissection adenotonsillectomy.\n In this double-blinded, placebo-controlled study, we examined the efficacy of a single dose of dexamethasone 0.5 mg/kg IV on posttonsillectomy vomiting and oral intake in children 2-12 yr old. Dexamethasone significantly decreased the incidence of postoperative vomiting during the first 24 h, shortened the time to the first oral intake and the duration of IV hydration, and improved the quality of oral intake and the satisfaction scores of the patients.", "Postoperative morbidity in patients undergoing tonsillectomy with or without adenoidectomy includes inadequate oral intake, pain, nausea, vomiting and bleeding. The purpose of this study is to evaluate the effect of preoperative 0.5 mg/kg i.v. dexamethasone on postoperative early oral intake, pain, vomiting in patients undergoing adenotonsillectomy while performing standard anesthesia technique and sharp dissection tonsillectomy.\n In this prospective, double-blinded, placebo-controlled study 62 children, aged 4-12 years, who underwent tonsillectomy with or without adenoidectomy were randomly assigned to receive single dose of 0.5 mg/kg i.v. dexamethasone preoperatively. Patients started to receive 100 ml of clear fluids 2 h postoperatively, then were offered every hour. When pain score was 3 or above, paracetamol was given for pain control. Tolerating 400 ml of clear fluids, no bleeding and no vomiting were accepted as discharge criteria. The discharge time was also recorded. The incidence of early vomiting, pain scores, amount of oral intake were recorded until the discharge time.\n Compared with placebo, the patients who received preoperative dexamethasone had significantly less pain score during the first 6 h postoperatively (p<0.05), adequate amount of oral intake time was shorter (p<0.05) and the discharge time was earlier (p<0.05). No difference was found in vomiting incidence in both groups.\n Preoperative dexamethasone use significantly reduces early posttonsillectomy pain, improves oral intake and facilitates meeting the discharge criteria while using standard anesthesia technique and sharp dissection tonsillectomy without any significant side effects.", "A prospective, randomized, double-blinded, placebo-controlled clinical trial was conducted in 41 patients evaluating the effect of a single preoperative dose of intravenous dexamethasone on postoperative vomiting and pain in children undergoing elective tonsillectomy. Dexamethasone was found to significantly reduce the incidence of vomiting in the first 24 hours postoperatively (P = 0.02), the time to first intake of solids (P = 0.001), the need to administer a rescue antiemetic (P = 0.005) and intravenous fluid therapy requirements (P = 0.006) in the postoperative period. No significant difference was found between the dexamethasone and placebo groups in the time to first intake of fluids, pain scores or analgesic requirement postoperatively. These results indicate that dexamethasone substantially reduces morbidity after tonsillectomy in children." ]

[ "19036752" ]

[ "High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients." ]

[ "The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial.\n Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infected patients with a CD4 count <350/mm(3). We planned to enroll 250 patients.\n As of May 2006, 71 patients had been enrolled (35 in Group 1 and 36 in Group 2) and an unplanned interim analysis was done. The groups were comparable at baseline: median CD4 count was 195 and 191/mm(3) and median plasma viral load was 4.9 log(10) and 5.01 log(10), respectively, in Groups 1 and 2. Eight early non-responses (22.2%) were observed, all in Group 2, while two later viral rebounds occurred. Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I (n = 3), K65R (n = 6), one or more NNRTI resistance mutations in all cases. At baseline, the nine Group 2 patients who failed had higher median plasma viral load (5.4 log(10)) and lower median CD4 count (110/mm(3)) than the other Group 2 patients (4.7 log(10), P = 0.002 and 223/mm(3), P = 0.004). Nevirapine trough concentrations were not different between the two groups, nor between patients with full viral suppression or those who failed in Group 2. Due to slow recruitment, and those results, the steering committee decided to stop the trial at 12 months.\n In ARV-naive HIV-1-infected patients, the once-daily lamivudine, tenofovirDF and nevirapine regimen resulted in a high rate of early virological failures. The reasons for the failures remain unclear." ]

[ "15961713", "17909152", "18478129", "18309164" ]

[ "The Early Systemic Prophylaxis of Infection After Stroke study: a randomized clinical trial.", "Minocycline treatment in acute stroke: an open-label, evaluator-blinded study.", "Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial.", "Effects of prophylactic antibiotic therapy with mezlocillin plus sulbactam on the incidence and height of fever after severe acute ischemic stroke: the Mannheim infection in stroke study (MISS)." ]

[ "Early infection after stroke is frequent but the clinical value of antibiotic prophylaxis in acute stroke has never been explored.\n The Early Systemic Prophylaxis of Infection After Stroke (ESPIAS) is a randomized, double-blind, placebo-controlled study of antibiotic prophylaxis in patients older than 18 years with nonseptic ischemic or hemorrhagic stroke enrolled within 24 hours from clinical onset. Interventions included intravenous levofloxacin (500 mg/100 mL/d, for 3 days) or placebo (0.9% physiological serum) in addition to optimal care. A sample size of 240 patients was calculated to identify a 15% absolute risk reduction of the primary outcome measure, which was the incidence of infection at day 7 after stroke. Secondary outcome measures were neurological outcome and mortality at day 90.\n Based on a preplanned futility analysis, the study was interrupted prematurely when 136 patients had been included. Levofloxacin and placebo patients had a cumulative rate of infection of 6% and 6% (P=0.96) at day 1; 10% and 12% (P=0.83) at day 2; 12% and 15% (P=0.66) at day 3; 16% and 19% (P=0.82) at day 7; and 30% and 33% (P=0.70), at day 90. Using logistic regression, favorable outcome at day 90 was inversely associated with baseline National Institutes of Health Stroke Scale (OR, 0.72; 95% CI, 0.59 to 0.89; P=0.002) and allocation to levofloxacin (OR, 0.19; 95% CI, 0.04 to 0.87; P=0.03).\n Prophylactic administration of levofloxacin (500 mg/100 mL/day for 3 days) is not better than optimal care for the prevention of infections in patients with acute stroke.", "Ischemic animal model studies have shown a neuroprotective effect of minocycline.\n To analyze the effect of minocycline treatment in human acute ischemic stroke.\n We performed an open-label, evaluator-blinded study. Minocycline at a dosage of 200 mg was administered orally for 5 days. The therapeutic window of time was 6 to 24 hours after onset of stroke. Data from NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) were evaluated. The primary objective was to compare changes from baseline to day 90 in NIHSS in the minocycline group vs placebo.\n One hundred fifty-two patients were included in the study. Seventy-four patients received minocycline treatment, and 77 received placebo. NIHSS and mRS were significantly lower and BI scores were significantly higher in minocycline-treated patients. This pattern was already apparent on day 7 and day 30 of follow-up. Deaths, myocardial infarctions, recurrent strokes, and hemorrhagic transformations during follow-up did not differ by treatment group.\n Patients with acute stroke had significantly better outcome with minocycline treatment compared with placebo. The findings suggest a potential benefit of minocycline in acute ischemic stroke.", "Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients.\n Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance.\n On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections.\n PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections.\n Controlled-Trials.com ISRCTN74386719.", "Fever after stroke is a strong predictor for a negative outcome with infections as the most common cause. The aim of this pilot study was to evaluate the effects of prophylactic antibiotic therapy on the incidence and height of fever after acute ischemic stroke.\n This is a randomized, controlled study of antibiotic prophylaxis in patients with ischemic stroke enrolled within 24 hours from clinical onset who presented bedridden (modified Rankin score >3) with no significant infection. Interventions included prophylactic mezlocillin plus sulbactam (3 x 2 g/1 g for 4 days) or conventional management. Over 10 days, body temperature was continuously monitored, and the presence of infection was daily assessed. Primary end points were incidence and height of fever; secondary end points included rate of infection and clinical outcome.\n Sixty patients were included (mean, 75 years; median National Institutes of Health Stroke Scale score, 16). Over the first 3 days, patients in the intervention group showed lower mean body temperatures as well as lower daily peak temperatures (P<0.05). Throughout the observation period, 15 of 30 patients in the intervention group but 27 of 30 patients in the conventionally treated group developed an infection (P<0.05). Mean interval until the diagnosis of infection was 5.1 days in the intervention group and 3.3 days in the control group (P<0.05). Clinical outcome was more favorable in patients with prophylactic therapy (P=0.01).\n In patients with acute severe stroke, prophylactic administration of mezlocillin plus sulbactam over 4 days decreases body temperature, lowers the rate of infection, and may be associated with a better clinical outcome." ]

[ "18714059", "18460663", "20571015", "16531613", "19118243", "12821232", "16531614", "14975544", "14762035", "20688574" ]

[ "Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial.", "Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial.", "Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial.", "Homocysteine lowering with folic acid and B vitamins in vascular disease.", "High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial.", "Secondary prevention with folic acid: effects on clinical outcomes.", "Homocysteine lowering and cardiovascular events after acute myocardial infarction.", "Efficacy of folic acid when added to statin therapy in patients with hypercholesterolemia following acute myocardial infarction: a randomised pilot trial.", "Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial.", "B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial." ]

[ "Observational studies have reported associations between circulating total homocysteine concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B(12) can lower plasma total homocysteine levels.\n To assess the effect of treatment with folic acid and vitamin B(12) and the effect of treatment with vitamin B(6) as secondary prevention in patients with coronary artery disease or aortic valve stenosis.\n Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double- or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes.\n Using a 2 x 2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B(12), 0.4 mg, plus vitamin B(6), 40 mg (n = 772); folic acid plus vitamin B(12) (n = 772); vitamin B(6) alone (n = 772); or placebo (n = 780).\n The primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke.\n Mean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B(12). The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B(12) vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P = .36) and 200 participants (13.0%) receiving vitamin B(6) vs 222 (14.3%) not receiving vitamin B(6) (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P = .28).\n This trial did not find an effect of treatment with folic acid/vitamin B(12) or vitamin B(6) on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease.\n clinicaltrials.gov Identifier: NCT00354081.", "Recent randomized trials among patients with preexisting cardiovascular disease (CVD) have failed to support benefits of B-vitamin supplementation on cardiovascular risk. Observational data suggest benefits may be greater among women, yet women have been underrepresented in published randomized trials.\n To test whether a combination of folic acid, vitamin B6, and vitamin B12 lowers risk of CVD among high-risk women with and without CVD.\n Within an ongoing randomized trial of antioxidant vitamins, 5442 women who were US health professionals aged 42 years or older, with either a history of CVD or 3 or more coronary risk factors, were enrolled in a randomized, double-blind, placebo-controlled trial to receive a combination pill containing folic acid, vitamin B6, and vitamin B12 or a matching placebo, and were treated for 7.3 years from April 1998 through July 2005.\n Daily intake of a combination pill of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12.\n A composite outcome of myocardial infarction, stroke, coronary revascularization, or CVD mortality.\n Compared with placebo, a total of 796 women experienced a confirmed CVD event (406 in the active group and 390 in the placebo group). Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point (226.9/10,000 person-years vs 219.2/10,000 person-years for the active vs placebo group; relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.19; P = .65), as well as for the secondary outcomes including myocardial infarction (34.5/10,000 person-years vs 39.5/10,000 person-years; RR, 0.87; 95% CI, 0.63-1.22; P = .42), stroke (41.9/10,000 person-years vs 36.8/10,000 person-years; RR, 1.14; 95% CI, 0.82-1.57; P = .44), and CVD mortality (50.3/10,000 person-years vs 49.6/10,000 person-years; RR, 1.01; 95% CI, 0.76-1.35; P = .93). In a blood substudy, geometric mean plasma homocysteine level was decreased by 18.5% (95% CI, 12.5%-24.1%; P < .001) in the active group (n = 150) over that observed in the placebo group (n = 150), for a difference of 2.27 micromol/L (95% CI, 1.54-2.96 micromol/L).\n After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering.\n clinicaltrials.gov Identifier: NCT00000541.", "Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal.\n To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12) on vascular and nonvascular outcomes.\n Double-blind randomized controlled trial of 12,064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008.\n 2 mg folic acid plus 1 mg vitamin B(12) daily vs matching placebo.\n First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization.\n Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B(12) vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]).\n Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence.\n isrctn.org Identifier: ISRCTN74348595.", "In observational studies, lower homocysteine levels are associated with lower rates of coronary heart disease and stroke. Folic acid and vitamins B6 and B12 lower homocysteine levels. We assessed whether supplementation reduced the risk of major cardiovascular events in patients with vascular disease.\n We randomly assigned 5522 patients 55 years of age or older who had vascular disease or diabetes to daily treatment either with the combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or with placebo for an average of five years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, and stroke.\n Mean plasma homocysteine levels decreased by 2.4 micromol per liter (0.3 mg per liter) in the active-treatment group and increased by 0.8 micromol per liter (0.1 mg per liter) in the placebo group. Primary outcome events occurred in 519 patients (18.8 percent) assigned to active therapy and 547 (19.8 percent) assigned to placebo (relative risk, 0.95; 95 percent confidence interval, 0.84 to 1.07; P=0.41). As compared with placebo, active treatment did not significantly decrease the risk of death from cardiovascular causes (relative risk, 0.96; 95 percent confidence interval, 0.81 to 1.13), myocardial infarction (relative risk, 0.98; 95 percent confidence interval, 0.85 to 1.14), or any of the secondary outcomes. Fewer patients assigned to active treatment than to placebo had a stroke (relative risk, 0.75; 95 percent confidence interval, 0.59 to 0.97). More patients in the active-treatment group were hospitalized for unstable angina (relative risk, 1.24; 95 percent confidence interval, 1.04 to 1.49).\n Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017.).\n Copyright 2006 Massachusetts Medical Society.", "Although plasma total homocysteine (tHcy) levels are associated with cardiovascular disease, it remains unclear whether homocysteine is a cause or a marker of atherosclerotic vascular disease. We determined whether reduction of tHcy levels with B vitamin supplementation reduces subclinical atherosclerosis progression.\n In this double-blind clinical trial, 506 participants 40 to 89 years of age with an initial tHcy >8.5 micromol/L without diabetes and cardiovascular disease were randomized to high-dose B vitamin supplementation (5 mg folic acid+0.4 mg vitamin B(12)+50 mg vitamin B(6)) or matching placebo for 3.1 years. Subclinical atherosclerosis progression across 3 vascular beds was assessed using high-resolution B-mode ultrasonography to measure carotid artery intima media thickness (primary outcome) and multidetector spiral CT to measure aortic and coronary artery calcium (secondary outcome).\n Although the overall carotid artery intima media thickness progression rate was lower with B vitamin supplementation than with placebo, statistically significant between-group differences were not found (P=0.31). However, among subjects with baseline tHcy >or=9.1 micromol/L, those randomized to B vitamin supplementation had a statistically significant lower average rate of carotid artery intima media thickness progression compared with placebo (P=0.02); among subjects with a baseline tHcy <9.1 micromol/L, there was no significant treatment effect (probability value for treatment interaction=0.02). B vitamin supplementation had no effect on progression of aortic or coronary artery calcification overall or within subgroups.\n High-dose B vitamin supplementation significantly reduces progression of early-stage subclinical atherosclerosis (carotid artery intima media thickness) in well-nourished healthy B vitamin \"replete\" individuals at low risk for cardiovascular disease with a fasting tHcy >or=9.1 micromol/L.", "We sought to conduct a randomized trial with folic acid 0.5 mg/day in a patient population with stable coronary artery disease (CAD).\n Folic acid has favorable effects on vascular endothelium and lowers plasma homocysteine levels. In addition, homocysteine appears to be an independent risk factor for atherosclerotic disease. However, the value of folic acid in secondary prevention had seldom been tested.\n In this open-label study, 593 patients were included; 300 were randomized to folic acid and 293 served as controls. Mean follow-up time was 24 months. At baseline all patients had been on statin therapy for a mean of 3.2 years.\n In patients treated with folic acid, plasma homocysteine levels decreased by 18%, from 12.0 +/- 4.8 to 9.4 +/- 3.5 micromol/l, whereas these levels remained unaffected in the control group (p < 0.001 between groups). The primary end point (all-cause mortality and a composite of vascular events) was encountered in 31 (10.3%) patients in the folic acid group and in 28 (9.6%) patients in the control group (relative risk 1.05; 95% confidence interval: 0.63 to 1.75). In a multifactorial survival model with adjustments for clinical factors, the most predictive laboratory parameters were, in order of significance, levels of creatinine clearance, plasma fibrinogen, and homocysteine.\n Within two years, folic acid does not seem to reduce clinical end points in patients with stable coronary artery disease (CAD) while on statin treatment. Homocysteine might therefore merely be a modifiable marker of disease. Thus, low-dose folic acid supplementation should be treated with reservation, until more trial outcomes become available.", "Homocysteine is a risk factor for cardiovascular disease. We evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients who had had an acute myocardial infarction.\n The trial included 3749 men and women who had had an acute myocardial infarction within seven days before randomization. Patients were randomly assigned, in a two-by-two factorial design, to receive one of the following four daily treatments: 0.8 mg of folic acid, 0.4 mg of vitamin B12, and 40 mg of vitamin B6; 0.8 mg of folic acid and 0.4 mg of vitamin B12; 40 mg of vitamin B6; or placebo. The primary end point during a median follow-up of 40 months was a composite of recurrent myocardial infarction, stroke, and sudden death attributed to coronary artery disease.\n The mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12, but such treatment had no significant effect on the primary end point (risk ratio, 1.08; 95 percent confidence interval, 0.93 to 1.25; P=0.31). Also, treatment with vitamin B6 was not associated with any significant benefit with regard to the primary end point (relative risk of the primary end point, 1.14; 95 percent confidence interval, 0.98 to 1.32; P=0.09). In the group given folic acid, vitamin B12, and vitamin B6, there was a trend toward an increased risk (relative risk, 1.22; 95 percent confidence interval, 1.00 to 1.50; P=0.05).\n Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested. Such treatment should therefore not be recommended. (ClinicalTrials.gov number, NCT00266487.).\n Copyright 2006 Massachusetts Medical Society.", "Folic acid is assumed to have favourable effects on vascular endothelium, directly as well as indirectly through its effect on homocysteine metabolism. However, the clinical value of folic acid in secondary prevention after acute myocardial infarction (MI) has never been tested. Thus, a randomised, open-label, multicentre trial was performed in order to study the effect of folic acid 5 mg o.d. when added to statin therapy on the incidence of recurrent major clinical events up to 1 year post-MI.\n A total of 283 patients with a total cholesterol >6.5 mmol/l (251 mg/dl) (mean 7.3 mmol/l) were included. All patients received 40 fluvastatin. In 140 of the 283 patients, folic acid (5 mg o.d.) was instituted at discharge, and the remaining 143 patients served as controls. Other secondary prevention measures for both groups were advocated. The primary endpoint was a composite consisting of all vascular events, including death, recurrent MI, strokes, and unplanned invasive coronary interventions.\n At baseline, the two groups were well-matched for all clinical and demographic parameters. After 1 year of treatment, no difference was noticed in the primary endpoint between the two groups. These endpoints occurred in 43 patients (31%) in the folic acid group, as opposed to 45 patients (31%) in the control group. All separate cardiovascular events were also equally distributed between both groups. Total cholesterol levels decreased to a similar extent in the two groups (to 5.5 and 5.7 mmol/l, in folic acid and control groups, respectively).\n In this medium-size pilot study, folic acid did not demonstrate any beneficial additive effects on cardiovascular mortality or morbidity in post-MI patients with hypercholesterolemia who were treated with statin therapy. Larger trials, possibly targeting at selected populations, must be awaited before definitive conclusions regarding the potentially favourable effects of folic acid supplementation in secondary prevention can be drawn.", "In observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk. However the utility of homocysteine-lowering therapy to reduce that risk has not been confirmed by randomized trials.\n To determine whether high doses of folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins.\n Double-blind randomized controlled trial (September 1996-May 2003).\n 3680 adults with nondisabling cerebral infarction at 56 university-affiliated hospitals, community hospitals, private neurology practices, and Veterans Affairs medical centers across the United States, Canada, and Scotland.\n All participants received best medical and surgical care plus a daily multivitamin containing the US Food and Drug Administration's reference daily intakes of other vitamins; patients were randomly assigned to receive once-daily doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine, 0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation (n = 1853), containing 200 microg of pyridoxine, 6 microg of cobalamin and 20 microg of folic acid.\n Recurrent cerebral infarction (primary outcome); coronary heart disease (CHD) events and death (secondary outcomes).\n Mean reduction of total homocysteine was 2 micromol/L greater in the high-dose group than in the low-dose group, but there was no treatment effect on any end point. The unadjusted risk ratio for any stroke, CHD event, or death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P =.80 by log-rank test of the primary hypothesis of difference in ischemic stroke between treatment groups). There was a persistent and graded association between baseline total homocysteine level and outcomes. A 3- micromol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P =.05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P =.001) in the low-dose group and a nonsignificantly lower risk in the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death.\n In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. However, the consistent findings of an association of total homocysteine with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary.", "Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye.\n In this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0.5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratified by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT00097669, and Current Controlled Trials, ISRCTN74743444.\n Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3.4 years (IQR 2.0-5.5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0.91, 95% CI 0.82 to 1.00, p=0.05; absolute risk reduction 1.56%, -0.01 to 3.16). There were no unexpected serious adverse reactions and no significant differences in common adverse effects between the treatment groups.\n Daily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins.\n Australia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, Singapore National Medical Research Council, Australia National Heart Foundation, Royal Perth Hospital Medical Research Foundation, and Health Department of Western Australia.\n Copyright 2010 Elsevier Ltd. All rights reserved." ]

[ "11336163", "17059514" ]

[ "Does adjuvant nutritional support diminish steroid dependency in Crohn disease?", "Effectiveness of an 'half elemental diet' as maintenance therapy for Crohn's disease: A randomized-controlled trial." ]

[ "Nutritional therapy plays an important role in the management of Crohn disease, particularly during the acute phase. Nutritional supplementation may also prevent relapses during the quiescent phase of Crohn disease, though this aspect has not been widely explored.\n Thirty-three patients with Crohn disease in remission were studied. All had steroid-dependent disease. Patients were randomized to receive either elemental diet (n = 19, EO28 Extra) or polymeric diet (Forticips, n = 14). The supplement was given orally in addition to normal food in an amount to provide 35%-50% of pre-trial total calorie intake. Prednisolone was withdrawn gradually. Patients were followed up for 12 months. Failure was defined as increase in CDAI by 100 points from baseline to >200, inability to withdraw chronic steroid therapy completely, need for surgery or steroid therapy.\n The nutritional supplement was successful in 14 (43%) patients who remained in remission for 12 months with complete withdrawal of steroids. The response to elemental diet (42%) was similar to that of polymeric diet (43%). Nutrition supplement failed in 13 (39%). Six (18%) patients were intolerant to enteral feeding because of smell and taste problems. Per-protocol analysis of data indicated that the success rate of nutrition supplement in steroid-dependent patients was 52% (14 out of 27 patients). No disease or patient-related factors helped predict the response to nutrition supplement.\n Nutritional supplementation with either an elemental or polymeric diet may provide a safe and effective alternative to chronic steroid therapy in patients with steroid-dependent Crohn disease.", "Although thiopurines have a proven role in maintenance therapy for Crohn's disease, an alternative therapy is needed for patients intolerant or resistant to thiopurines.\n To evaluate the effectiveness of home enteral nutrition as a maintenance therapy regimen in which half of the daily calorie requirement is provided by an elemental diet and the remaining half by a free diet. We refer to this home enteral nutrition therapy as 'half elemental diet'.\n Between 2002 and 2005, 51 patients in remission from two hospitals were randomly assigned to a half elemental diet group (n = 26) or a free diet group (n = 25). The primary outcome measure of this study was the occurrence of relapse over the 2-year period.\n The relapse rate in the half elemental diet group was significantly lower [34.6% vs. 64.0%; multivariate hazard ratio 0.40 (95% CI: 0.16-0.98)] than that in the free diet group after a mean follow-up of 11.9 months. Compliance was similar in the two groups. No adverse event occurred in any of the patients throughout the study.\n This randomized-controlled trial shows the effectiveness of an half elemental diet, which is a promising maintenance therapy for Crohn's disease patients." ]

[ "17364516", "19628801", "19801055" ]

[ "Computerized working memory training after stroke--a pilot study.", "Reducing attention deficits after stroke using attention process training: a randomized controlled trial.", "Efficacy of time pressure management in stroke patients with slowed information processing: a randomized controlled trial." ]

[ "To examine the effects of working memory (WM) training in adult patients with stroke.\n A randomized pilot study with a treatment group and a passive control group; 18 participants (12 males) in a vocational age group (mean age 54 years) were randomized to either the treatment or the control condition. The intervention consisted of computerized training on various WM tasks for five weeks. A neuropsychological test battery and self-rating on cognitive functioning in daily life (the CFQ) were administered both before and after the treatment.\n Statistically significant training effects were found on the non-trained tests for WM and attention, i.e., tests that measure related cognitive functions but are not identical to tasks in the training programme (Span board p < 0.05; PASAT p < 0.001; Ruff 2&7 p < 0.005). There was a significant decrease in symptoms of cognitive problems as measured by the CFQ (p < 0.005). Conclusion: More than one year after a stroke, systematic WM training can significantly improve WM and attention.", "Impaired attention contributes to poor stroke outcomes. Attention process training (APT) reduces attention deficits after traumatic brain injury. There was no evidence for effectiveness of APT in stroke patients. This trial evaluated effectiveness of APT in improving attention and broader outcomes in stroke survivors 6 months after stroke.\n Participants in this prospective, single-blinded, randomized, clinical trial were 78 incident stroke survivors admitted over 18 months and identified via neuropsychological assessment as having attention deficit. Participants were randomly allocated to standard care plus up to 30 hours of APT or standard care alone. Both groups were impaired (z < or = -2.0) across measures of attention at baseline, with the exception of Paced Auditory Serial Addition Test, which was below average (z < or = -1.0). Outcome assessment occurred at 5 weeks and 6 months after randomization. The primary outcome was Integrated Visual Auditory Continuous Performance Test Full-Scale Attention Quotient.\n APT resulted in a significantly greater (P<0.01) improvement on the primary outcome than standard care. Difference in change on the Cognitive Failures Questionnaire approached significance (P=0.07). Differences on other measures of attention and broader outcomes were not significant.\n APT is a viable and effective means of improving attention deficits after incident stroke.", "Winkens I, Van Heugten CM, Wade DT, Habets EJ, Fasotti L. Efficacy of Time Pressure Management in stroke patients with slowed information processing: a randomized controlled trial.\n To examine the effects of a Time Pressure Management (TPM) strategy taught to stroke patients with mental slowness, compared with the effects of care as usual.\n Randomized controlled trial with outcome assessments conducted at baseline, at the end of treatment (at 5-10wk), and at 3 months.\n Eight Dutch rehabilitation centers.\n Stroke patients (N=37; mean age +/- SD, 51.5+/-9.7y) in rehabilitation programs who had a mean Barthel score +/- SD at baseline of 19.6+/-1.1.\n Ten hours of treatment teaching patients a TPM strategy to compensate for mental slowness in real-life tasks.\n Mental Slowness Observation Test and Mental Slowness Questionnaire.\n Patients were randomly assigned to the experimental treatment (n=20) and to care as usual (n=17). After 10 hours of treatment, both groups showed a significant decline in number of complaints on the Mental Slowness Questionnaire. This decline was still present at 3 months. At 3 months, the Mental Slowness Observation Test revealed significantly higher increases in speed of performance of the TPM group in comparison with the care-as-usual group (t=-2.7, P=.01).\n Although the TPM group and the care-as-usual group both showed fewer complaints after a 3-month follow-up period, only the TPM group showed improved speed of performance on everyday tasks. Use of TPM treatment therefore is recommended when treating stroke patients with mental slowness." ]

[ "11165126", "12050495", "14746858", "15015612", "15154663", "12667306", "11347286" ]

[ "The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial.", "Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial.", "Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis.", "Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial.", "The standardised mistletoe extract PS76A2 improves QoL in patients with breast cancer receiving adjuvant CMF chemotherapy: a randomised, placebo-controlled, double-blind, multicentre clinical trial.", "The influence of isorel on the advanced colorectal cancer.", "Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study." ]

[ "The effect of an adjuvant mistletoe extract treatment was tested in a prospective, randomised controlled clinical trial involving 477 patients with head and neck squamous cell carcinoma. The patients were stratified into two treatment groups that underwent surgery or surgery followed by radiotherapy and both groups were randomised for additional treatment with mistletoe extract. Patients treated with a mistletoe lectin-1 (ML-1) standardised mistletoe preparation had no lower risk of local/locoregional recurrences, distant metastases or second primaries. In the main analysis based on 202 patients treated with surgery and 275 patients treated with surgery and radiotherapy the adjusted hazard ratio for the disease-free survival (DFS) was 0.959 (95% confidence interval (CI) 0.725-1.268). The 5-year survival rates of patients from the mistletoe group were no better than the survival rates of patients from the control group. Furthermore, no significant changes in the cellular immune reaction or in quality of life could be detected. We conclude that the used mistletoe preparation has no indication in the adjuvant treatment of patients with head and neck cancer.", "The indication for topic chemotherapy or immunotherapy for well differentiated, noninvasive superficial bladder cancer remains controversial. Side effects of these treatments promoted use of unconventional therapies with cytokines, immunomodulators and mistletoe extracts. However, there are no controlled clinical data available on the efficacy of these extracts for bladder cancer. We evaluate the influence of subcutaneously applicated mistletoe lectin on bladder tumor recurrence after transurethral resection.\n The study consists of 45 patients with pTa G1-2 bladder cancer treated with transurethral resection during a 3-year period. Median patient age was 65 years and 33 patients were male. The study cohort was randomly divided into a treatment group receiving adjuvant therapy with mistletoe lectin and a control group receiving no additional treatment. Patients in the treatment group received mistletoe lectin according to schedule 2 weeks after transurethral resection. Clinical followup was assessed 3, 6, 9, 12 and 18 months after the initial resection, and included uretherocystoscopy.\n Both study arms comprised similar patients with regard to total number of previous tumors (mean 2.6 versus 2.9), number of primary lesions (14 versus 12) and number of recurrent tumors (8 versus 11). After followup of 18 months the recurrence-free interval in both study arms was similar (p = 0.76) and the total number of recurrences comparable (p = 0.48).\n Subcutaneous use of mistletoe lectin as adjuvant treatment after transurethral resection does not seem to affect the time to first recurrence, total number of recurrences or recurrence-free outcome.", "Between 1988 and 1996, the European Organisation for Research and Treatment of Cancer Melanoma Group (EORTC-MG) performed a prospective, randomised phase III adjuvant trial to evaluate the efficacy and toxicity of low dose recombinant interferon-alpha 2 b (rIFN-alpha2b) (1 MU) or recombinant interferon gamma (rIFN-gamma), (0.2 mg) both given subcutaneously (s.c.), every other day (qod), for 12 months in comparison with an untreated control group. The German Cancer Society (DKG) added a fourth arm with Iscador M, a popular mistletoe extract. High-risk stage II patients (thickness >3 mm) and stage III patients (positive lymph nodes) without distant metastasis were randomised and followed until their first progression or death. An intention-to-treat analysis was performed. From 1988 to 1996, a total of 830 patients were randomised: 423 in the three-arm EORTC 18871 trial and 407 patients in the four-arm DKG 80-1 trial. The median follow-up was 8.2 years and a total of 537 relapses and 475 deaths were reported. At 8 years, the disease-free interval (DFI) rate was 32.4% and the overall survival (OS) rate was 40.0%. In terms of the DFI, the hazard ratio estimates (95% Confidence Intervals (CI)) were: 1.04 (0.84, 1.30) for the comparison of rIFN-alpha2b versus control, 0.96 (0.77, 1.20) for rIFN-gamma versus control, and 1.32 (0.93, 1.87) for Iscador M versus control. In terms of OS, the corresponding estimates (95% CI) for the 3 treatment comparisons were: for IFN-alpha2b 0.96 (0.76, 1.21), for rIFN-gamma 0.87 (0.69, 1.10) and for Iscador M 1.21 (0.84, 1.75), respectively. The results show no clinical benefit for adjuvant treatment with low dose rIFN-alpha2b or rIFN-gamma or with Iscador M in high-risk melanoma patients.", "Standardized aqueous mistletoe extracts have been applied to cancer patients for several decades as complementary medicine. A multicentric, randomized, open, prospective clinical trial was conducted in three oncological centers in the People's Republic of China in Bejing, Shenyang and Tianjin. Following the guidelines of \"Good Clinical Practice\" (GCP) this study was performed to get information on efficacy safety and side-effects of the standardized mistletoe extract (sME). Two hundred and thirty-three patients with breast (n=68), ovarian (n=71) and non-small cell lung cancer (NSCLC; n=94) were enrolled into this study. Two hundred and twenty-four patients fulfilled the requirements for final analysis (n=115 treated with sME HELIXOR A; n=109 comprising the control group being treated with the approved immunomodulating phytopharmacon Lentinan). All patients were provided with standard tumor-destructive treatment schedules and complementarily treated with sME or Lentinan during chemotherapy according to treatment protocol. Biometrically, the patients of the control and sME treatment group were comparable regarding distribution, clinical classification (WHO) and treatment protocols. Analysis was performed according to the \"Intention to treat principle\". Quality of life (QoL) was significantly (p<0.05) improved for patients who were complementarily treated with sME, as determined by the questionnaires FLIC (Functional Living Index-Cancer), TCM (Traditional Chinese Medicine Index) and the KPI (Karnofsky Performance Index) in comparison to the control group. Additionally, the occurrence of adverse events (AEs) was less frequent in the sME than in the control group (total number of AEs 52 versus 90 and number of serious AEs 5 versus 10 in study and control group, most of them due to chemotherapy). Only one serious AE was allocated to complementary treatment in each group (1 angioedema in sME group). All other side-effects of the sME (7 harmless local inflammatory reactions at subcutaneous injection site, 4 cases with fever) were self-limiting and did not demand therapeutic intervention. This study showed that complementary treatment with sME can beneficially reduce the side-effects of chemotherapy in cancer patients and thus improve quality of life.", "Patients with breast cancer receiving adjuvant chemotherapy frequently suffer from a restricted quality of life (QoL) due to the side-effects of chemotherapy and the consequences of coping with the diagnosis. Therefore, the objective of this clinical study was to investigate the impact of PS76A2, an aqueous mistletoe extract standardised to the galactoside-specific mistletoe lectin, on QoL by performing a placebo-controlled trial. Overall, 272 patients with breast cancer receiving adjuvant CMF chemotherapy (cyclophosphamide-methotrexate-fluorouracil) were enrolled and randomised to groups receiving placebo or PS76A2 at concentrations of 10, 30 or 70 ng mistletoe lectin (ML) per ml. The patients received 0.5 ml study medication twice weekly subcutaneously for 15 consecutive weeks (4 CMF cycles). Primary variables were the self-assessment QoL scores GLQ-8 (Global Life Quality) and Spitzer's uniscale. As a result, statistically significant effects on QoL were obtained with the medium dose (15 ng ML/0.5 ml). The treatment difference between the medium dose and placebo with regard to the GLQ-8 sum was 60.8 mm (95% confidence interval: 19.3 to 102.0 mm). The treatment effect for Spitzer's uniscale between the medium dose and placebo was 16.4 mm (95% confidence interval: 6.3 to 26.6 mm). The results on QoL were supported by an increase of T helper lymphocytes (CD4+) and the CD4+/CD8+ ratio (p<0.05). Overall, PS76A2 was well tolerated. Local reactions at the injection sites occurred dose-dependently, but were mild at the low and medium dose levels.", "There is still no therapy method in the colorectal cancers that is good enough for such a complex disease. Combined surgery, chemotherapy, and radiotherapy improved survival, but the side effects and the poor performance status of the patients seriously affect the use of these methods. We used a therapeutical approach of surgery and chemotherapy combined with biotherapy by Viscum album extract Isorel, aiming to improve the patients' resistance to the disease and to render the treatment's side effects more tolerable. Isorel is aqueous extract well known for its anticancer effects obtained by various in vitro and in vivo experimental models and which was validated by an in vitro bioassay on murine melanoma B16F10 and human cervical carcinoma HeLa cells. Isorel strongly reduced human colon cancer HT 29 cell line growth in vitro in the MTT bioassay. Hence, it was further used in a prospective, randomized, and controlled study which compared the postoperative results for patients with colorectal cancer stages Dukes C (40 patients) and D (24 patients) who, beside surgery, received either only chemotherapy (5-FU), 6 cycles (either the Mayo or the De Gramont protocol) or chemotherapy combined with Isorel biotherapy. These 64 patients were randomly allocated into three groups \"only chemotherapy\" for 21 cases, chemo + biotherapy for 29 cases and 14 patients underwent only surgery as the control group. We noted no toxic deaths due to either chemo or biotherapy. The patients operated on and treated with chemo and biotherapy had median survival significantly better and a cumulative proportion survival (Kaplan-Maier) superior to those of the patients receiving only postoperative chemotherapy. Thus, colorectal cancer patients seem to benefit in terms of survival from combined postoperative chemotherapy and Isorel biotherapy, either adjuvant or palliative.", "In anthroposophical medicine, total extracts of Viscum album (mistletoe) have been developed to treat cancer patients. The oldest such product is Iscador. Although Iscador is regarded as a complementary cancer therapy, it is the most commonly used oncological drug in Germany.\n To determine whether Iscador treatment prolongs survival time of patients with carcinoma of the colon, rectum, or stomach; breast carcinoma with or without axillary or remote metastases; or small cell or non-small-cell bronchogenic carcinoma; and to explore synergies between Iscador treatment and psychosomatic self-regulation.\n Prospective nonrandomized and randomized matched-pair studies nested within a cohort study.\n General community in Germany.\n 10,226 cancer patients involved in a prospective long-term epidemiological cohort study, including 1668 patients treated with Iscador and 8475 who had taken neither Iscador nor any other mistletoe product (control patients).\n Iscador.\n Survival time.\n In the nonrandomized matched-pair study, survival time of patients treated with Iscador was longer for all types of cancer studied. In the pool of 396 matched pairs, mean survival time in the Iscador groups (4.23 years) was roughly 40% longer than in the control groups (3.05 years; P < .001). Synergies between Iscador treatment and self-regulation manifested in a longer survival advantage for Iscador patients with good self-regulation (56% relative to control group; P = .03) than for patients with poor self-regulation. Results of the 2 randomized matched-pair studies largely confirmed the results of the non-randomized studies.\n Iscador treatment can achieve a clinically relevant prolongation of survival time of cancer patients and appears to stimulate self-regulation." ]

[ "22611116" ]

[ "Methods of weaning preterm babies <30 weeks gestation off CPAP: a multicentre randomised controlled trial." ]

[ "Controversy exists whether different continuous positive airway pressure (CPAP) weaning methods influence time to wean off CPAP, CPAP duration, oxygen duration, Bronchopulmonary Dysplasia (BPD) or length of admission.\n In a multicentre randomised controlled trial, the authors have primarily compared CPAP weaning methods impact on time to wean off CPAP and CPAP duration and secondarily their effect on oxygen duration, BPD and time of admission.\n Between April 2006 and October 2009, 177 infants <30 weeks gestational age (GA) who fulfilled stability criteria on CPAP were randomised to one of the three CPAP weaning methods (M). M1: Taken 'OFF' CPAP with the view to stay 'OFF'. M2: Cycled on and off CPAP with incremental time 'OFF'. M3: As with m(2), cycled on and off CPAP but during 'OFF' periods were supported by 2 mm nasal cannula at a flow of 0.5 l/min.\n Based on intention to treat analysis, there was no significant difference in mean GA or birthweight between the groups (27.1 ± 1.4, 26.9 ± 1.6 and 27.3 ± 1.5 (weeks ± 1SD) and 988 ± 247, 987 ± 249 and 1015 ± 257 (grams ± 1SD), respectively). Primary outcomes showed M1 produced a significantly shorter time to wean from CPAP (11.3 ± 0.8, 16.8 ± 1.0, 19.4 ± 1.3 (days ± 1SE) p<0.0001, respectively) and CPAP duration (24.4 ± 0.1, 38.6 ± 0.1, 30.5 ± 0.1 (days ± 1SE) p<0.0001, respectively). All the secondary outcomes were significantly shorter with M1, (oxygen duration: 24.1 ± 1.5, 45.8 ± 2.2, 34.1 ± 2.0 (days ± 1SE) p<0.0001, BPD: 7/56 (12.5%), 29/69 (42%), 10/52 (19%) p=0.011 and length of admission: 58.5 ± 0.1, 73.8 ± 0.1 69.5 ± 0.1 (days ± 1SE) p<0.0001, respectively).\n Method 1 significantly shortens CPAP weaning time, CPAP duration, oxygen duration, BPD and admission time." ]

[ "16203881", "7562150" ]

[ "Cementless calcar-replacement hemiarthroplasty compared with intramedullary fixation of unstable intertrochanteric fractures. A prospective, randomized study.", "Treatment of unstable peritrochanteric fractures in elderly patients with a compression hip screw or with the Vandeputte (VDP) endoprosthesis: a prospective randomized study." ]

[ "Unstable intertrochanteric fractures in elderly patients are associated with a high rate of complications. The purpose of this investigation was to compare the results of long-stem cementless calcar-replacement hemiarthroplasty with those of treatment with a proximal femoral nail for unstable intertrochanteric fractures in elderly patients.\n Fifty-eight elderly patients with an AO/OTA type 31-A2 intertrochanteric fracture of the femur were randomized into two treatment groups and were followed for a minimum of two years. The twenty-nine patients in Group I were treated with a long-stem cementless calcar-replacement prosthesis, and the twenty-nine patients in Group II were treated with a proximal femoral nail. The two treatment groups were comparable with regard to demographic and injury variables.\n There were no significant differences between the groups in terms of functional outcomes, hospital stay, time to weight-bearing, or general complications. Patients treated with a proximal femoral nail had a shorter operative time, less blood loss, fewer units of blood transfused, a lower mortality rate, and lower hospital costs compared with those treated with the long-stem cementless calcar-replacement prosthesis.\n In elderly patients with an unstable intertrochanteric femoral fracture, a proximal femoral nail provides superior clinical outcomes but no advantage with regard to functional outcome when compared with a long-stem cementless calcar-replacement arthroplasty.\n Therapeutic Level I.", "A prospective randomized study was set up, comparing a compression hip screw with the Vandeputte (VDP) endoprosthesis treatment for fresh, unstable peritrochanteric fractures, according to the Evans-Jensen and AO systems. Ninety patients, ages > or = 70 years, 47 of whom were treated with a compression hip screw and 43 with a VDP endoprosthesis, were included. All patients were being followed for 3 months. No difference between the two groups was found for operating time, wound complications, and mortality rate, but there was a higher transfusion need in VDP treatment. Severe fracture redisplacement or total collapse of the fracture occurred in 11 (26%) compression hip screw patients, two of whom had revision surgery. Only one patient needed reintervention after VDP treatment. Functional capacity of preoperative independent patients at hospital discharge did not differ for the two groups. In conclusion, the compression hip screw seemed to be an appropriate implant for most of the peritrochanteric fractures, but for very old patients with advanced osteoporosis, with a complex, unstable peritrochanteric fracture, and who are eligible for early mobilization, primary cemented endoprosthesis might be the best treatment." ]

[ "15832550", "16271570" ]

[ "Effects of constraint-induced movement therapy in young children with hemiplegic cerebral palsy: an adapted model.", "Efficacy of forced-use therapy in hemiplegic cerebral palsy." ]

[ "The aim of this study was to evaluate the effects of a modified version of constraint-induced (CI) movement therapy on bimanual hand-use in children with hemiplegic cerebral palsy (CP; age range 18 mo to 4 y) and to make a comparison with conventional paediatric treatment. Twenty-one children (13 females, eight males) completed the CI therapy programme and 20 children (12 males, eight females) served as a control group. Children in the CI therapy group were expected to wear a restraint glove for 2 hours each day over a period of 2 months. The training was based on principles of motor learning used in play and in motivational settings. To evaluate the effect of treatment, the Assisting Hand Assessment (AHA) was used. Assessments took place on three occasions: at onset, after 2 months, and 6 months after the first assessment. A significant interaction was found between group and AHA measure (ANOVA, F(2,74) = 5.64, p = 0.005). The children who received CI therapy improved their ability to use their hemiplegic hand significantly more than the children in the control group after 2 months, i.e. after treatment. Effect size was high after treatment and remained medium at 6 months. As the treatment was tailored to each child's capacity and interests, little frustration was experienced by the children.", "To determine the efficacy of forced-use therapy (FUT) on the improvement of upper-extremity function in children with hemiplegic cerebral palsy (CP).\n Prospective case series.\n Outpatient ambulatory clinic in South Korea.\n Thirty-one patients with hemiplegic CP were assigned to the FUT group (n=18) or to the control group (n=13). The mean age of the patients in the FUT group was 33.2 months and in the control group it was 43.2 months.\n The FUT group wore a short-arm Scotchcast on the unaffected arm for 6 weeks and also participated in a conventional rehabilitation program that included stretching exercises and functional occupational therapy for the upper extremity. The control group underwent the conventional rehabilitation program only.\n Hand function tests, including the box and block test (BBT), Erhardt Developmental Prehension Assessment (EDPA), and WeeFIM instrument taken before and after 6 weeks of treatment.\n Before treatment, there was no significant difference between groups in the BBT, EDPA, and WeeFIM scores. After 6 weeks of treatment, however, the FUT group showed significant improvement in the affected arm in the BBT and EDPA scores, compared with the control group (P<.05). The self-care score on the WeeFIM was also significantly improved in the FUT group (P<.05).\n FUT combined with a conventional rehabilitation program appears to be more effective than a rehabilitation program alone in improving affected hand function in children with hemiplegic CP." ]

[ "8980207" ]

[ "Moderate-intensity exercise and self-rated quality of sleep in older adults. A randomized controlled trial." ]

[ "To determine the effects of moderate-intensity exercise training on self-rated (subjective) sleep quality among healthy, sedentary older adults reporting moderate sleep complaints.\n Randomized controlled trial of 16 weeks' duration.\n General community.\n Volunteer sample of 29 women and 14 men (of 67 eligible subjects) aged 50 to 76 years who were sedentary, free of cardiovascular disease, and reported moderate sleep complaints. No participant was withdrawn for adverse effects.\n Randomized to 16 weeks of community-based, moderate-intensity exercise training or to a wait-listed control condition. Exercise consisted primarily of four 30- to 40-minute endurance training sessions (low-impact aerobics; brisk walking) prescribed per week at 60% to 75% of heart rate reserve based on peak treadmill exercise heart rate.\n Pittsburgh Sleep Quality Index (PSQI).\n Compared with controls (C), subjects in the exercise training condition (E) showed significant improvement in the PSQI global sleep score at 16 weeks (baseline and posttest values in mean [SD] for C=8.93 [3.1] and 8.8 [2.6]; baseline and posttest values for E=8.7 [3.0] and 5.4 [2.8]; mean posttest difference between conditions=3.4; P<.001; 95% confidence interval, 1.9-5.4), as well as in the sleep parameters of rated sleep quality, sleep-onset latency (baseline and posttest values for C=26.1 [20.0] and 23.8 [15.3]; for E=28.4 [20.2] and 14.6 [13.0]; net improvement=11.5 minutes), and sleep duration baseline and posttest scores for C=5.8 [1.1] and 6.0 [1.0]; for E=6.0 [1.1] and 6.8 [1.2]; net improvement=42 minutes) assessed via PSQI and sleep diaries (P=.05).\n Older adults with moderate sleep complaints can improve self-rated sleep quality by initiating a regular moderate-intensity exercise program." ]

[ "12015496", "9649101" ]

[ "A randomized controlled trial of early versus \"traditional\" postoperative oral intake after major abdominal gynecologic surgery.", "A randomized controlled trial of early postoperative feeding in gynecologic oncology patients undergoing intra-abdominal surgery." ]

[ "The purpose of this study was to compare early oral intake and the traditional timing of feeding after major gynecologic surgery and the effects on the length of hospital stay.\n Gynecologic oncology and urogynecology patients who underwent major abdominal gynecologic surgery were prospectively randomized to 1 of 2 groups. The traditional feeding group (group A, 49 patients) received nothing by mouth until documentation of bowel function. They were then advanced slowly to solid diet. The patients allocated to the early feeding regimen (group B, 47 patients) began clear fluids on the first postoperative day. Once 500 mL of clear fluid was tolerated, they received a regular diet. The groups were compared with regard to length of hospital stay, postoperative day that solids were tolerated, and the incidence of adverse effects. Statistical analyses were performed with the chi(2) test, the Fisher exact test, the Student t test, and analysis of variance.\n The demographic characteristics of the 2 groups were similar. There was a statistically significant reduction in the length of hospital stay for those patients on the early feeding regimen. The median length of stay for group A was 6.0 days and for group B was 4.0 days (P =.0001). There was no difference in the incidence of emesis, ileus, or other postoperative complications between the 2 groups.\n Early postoperative dietary advancement after major abdominal gynecologic surgery results in a decreased length of hospital stay and appears to be safe, with no increased adverse effects.", "To evaluate the safety and efficacy of early oral feeding after intra-abdominal surgery in gynecologic oncology patients.\n During a 1-year period, 200 gynecologic oncology patients undergoing intra-abdominal surgery were enrolled in a randomized controlled trial of early compared with traditional oral postoperative feeding. Patients allocated to early postoperative oral feeding began a clear liquid diet on the first postoperative day and then advanced to a regular diet as tolerated. Patients allocated to traditional postoperative oral feeding received nothing by mouth until return of bowel function (defined as the passage of flatus in the absence of vomiting or abdominal distention), then began a clear liquid diet, and advanced to a regular diet as tolerated.\n Age, case distribution, surgery length, blood loss, and first passage of flatus were similar in the early and traditional feeding groups. Significantly more patients in the early group developed nausea. Despite this, the incidence of vomiting, abdominal distention, incidence and duration of nasogastric tube use, and percentage of patients who tolerated clear liquid and regular diets on the first attempt were comparable in both groups. Time to development of bowel sounds, time to initiation of clear liquid and regular diets, and hospital stay were significantly longer in the traditional group. Major complications (eg, pneumonia, atelectasis, and wound complications) and febrile morbidity occurred equally in both groups. There were no known anastamotic complications or aspirations in either group. Postoperative changes in hematologic indices and electrolytes were comparable in both groups.\n Early postoperative feeding in gynecologic oncology patients undergoing intra-abdominal surgery is safe and well tolerated." ]

[ "2462069", "14581438", "2527401", "12359855", "9494595", "12947070", "7683480", "9328156" ]

[ "Palliation of painful bone metastases from prostate cancer using sodium etidronate: results of a randomized, prospective, double-blind, placebo-controlled study.", "Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer.", "Clodronate therapy of metastatic bone disease in patients with prostatic carcinoma.", "A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma.", "The analgesic efficacy of clodronate compared with placebo in patients with painful bone metastases from prostatic cancer.", "Randomized, double-blind, controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone and placebo in patients with hormone-refractory prostate cancer and pain.", "Evaluation of the effect of oral clodronate on skeletal metastases with type 1 collagen metabolites. A controlled trial of the Finnish Prostate Cancer Group.", "Concomitant i.v. and oral clodronate in the relief of bone pain--a double-blind placebo-controlled study in patients with prostate cancer." ]

[ "Sodium etidronate is a diphosphonate compound that inhibits bone resorption and mineralization. The drug has been reported to be highly effective for the palliation of painful bone metastasis from prostatic cancer. Fifty-seven patients were entered into a randomized, prospective, double-blind, placebo-controlled study of sodium etidronate. All patients had hormone refractory metastatic prostatic cancer and bone pain requiring analgesics. No difference was seen in the symptomatic response rate or analgesic requirement between patients treated with sodium etidronate and placebo. With the dose scheme used in this study sodium etidronate was ineffective for palliation of bone pain from prostatic cancer.", "Bone metastases occur in approximately 80% of patients with advanced prostate cancer. Pain is common in these patients. The purpose of this study was to evaluate the effect of an intravenous bisphosphonate, pamidronate disodium, on pain control in metastatic prostate cancer patients.\n Two multicenter, double-blind, randomized, placebo-controlled trials were conducted in patients with bone pain due to metastatic prostate cancer, with disease progression after first-line hormonal therapy. Intravenous pamidronate disodium (90 mg) or placebo was administered every 3 weeks for 27 weeks. Efficacy was measured via self-reported pain score (Brief Pain Inventory), analgesic use, the proportion of patients with a skeletal-related event (SRE; defined as pathologic fracture, radiation or surgery to bone, spinal cord compression, or hypercalcemia), and a pilot quantitative measurement of mobility. Laboratory evaluations included serum prostate-specific antigen, interleukin-6, bone alkaline phosphatase, and urinary bone resorption markers.\n Results of the two trials were pooled. There were no sustained significant differences between the pamidronate and placebo groups in self-reported pain measurements, analgesic use, proportion of patients with an SRE, or mobility at week 9 or 27. Urinary bone resorption markers were suppressed in the pamidronate group compared with placebo.\n Pamidronate disodium failed to demonstrate a significant overall treatment benefit compared with placebo in palliation of bone pain or reduction of SREs. Evaluation of more potent bisphosphonates in patients with prostate cancer is warranted.", "Metastatic bone disease represents the most disabling complication in patients with prostatic carcinoma. In an open multicenter trial 80 out of 92 patients with bone metastasis due to prostatic carcinoma experienced a dramatic improvement of bone pain after treatment with 300 mg clodronate infused intravenously daily for 10 days. Further to this, 56 patients were randomly allocated to four single-blind controlled therapeutic trials, assessing bone pain by daily consumption of analgesic drugs and by visual analogue scale. In the first protocol the effects of 2 weeks' treatment with intravenous infusion of either 300 mg clodronate dissolved in 500 ml saline (7 patients) or 500 ml saline (6 patients) were compared. The differences in both pain score and analgesic consumption were so striking that the trial was not extended for ethical reasons and all patients on placebo were given clodronate intravenously. Oral administration of 1200 mg clodronate for 2 weeks was completely ineffective in 11 patients. Intramuscular administration of 100 mg clodronate for 2 weeks induced in 12 patients a significant fall in analgesic consumption but not in the pain score. In most of the 13 patients given clodronate intravenously for 2 weeks bone pain relapsed fairly soon. However, in 18 patients a maintenance therapy with 1200 mg clodronate/day for at least 6 weeks after a 2-week intravenous treatment course did prevent the relapse of bone pain. In all patients given clodronate routine biochemical examination was carried out during and after treatment. For an overall follow-up of 42 patient-years hematologic toxicity was never observed. These results confirm that clodronate represents the most effective and convenient conservative treatment of patients with painful bone metastasis from prostatic carcinoma.", "Bone metastases are a common cause of morbidity in patients with prostate carcinoma. We studied the effect of a new bisphosphonate, zoledronic acid, which blocks bone destruction, on skeletal complications in prostate cancer patients with bone metastases.\n Patients with hormone-refractory prostate cancer and a history of bone metastases were randomly assigned to a double-blind treatment regimen of intravenous zoledronic acid at 4 mg (N = 214), zoledronic acid at 8 mg (subsequently reduced to 4 mg; 8/4) (N = 221), or placebo (N = 208) every 3 weeks for 15 months. Proportions of patients with skeletal-related events, time to the first skeletal-related event, skeletal morbidity rate, pain and analgesic scores, disease progression, and safety were assessed. All statistical tests were two-sided.\n Approximately 38% of patients who received zoledronic acid at 4 mg, 28% who received zoledronic acid at 8/4 mg, and 31% who received placebo completed the study. A greater proportion of patients who received placebo had skeletal-related events than those who received zoledronic acid at 4 mg (44.2% versus 33.2%; difference = -11.0%, 95% confidence interval [CI] = -20.3% to -1.8%; P =.021) or those who received zoledronic acid at 8/4 mg (38.5%; difference versus placebo = -5.8%, 95% CI = -15.1% to 3.6%; P =.222). Median time to first skeletal-related event was 321 days for patients who received placebo, was not reached for patients who received zoledronic acid at 4 mg (P =.011 versus placebo), and was 363 days for those who received zoledronic acid at 8/4 mg (P =.491 versus placebo). Compared with urinary markers in patients who received placebo, urinary markers of bone resorption were statistically significantly decreased in patients who received zoledronic acid at either dose (P =.001). Pain and analgesic scores increased more in patients who received placebo than in patients who received zoledronic acid, but there were no differences in disease progression, performance status, or quality-of-life scores among the groups. Zoledronic acid at 4 mg given as a 15-minute infusion was well tolerated, but the 8-mg dose was associated with renal function deterioration.\n Zoledronic acid at 4 mg reduced skeletal-related events in prostate cancer patients with bone metastases.", "Fifty-five patients with hormone refractory prostate cancer and painful bone metastases were randomised either to placebo or to clodronate 300 mg i.v. for 3 days, followed by oral clodronate 3200 mg for four weeks. Pain intensity was assessed using Visual Analogue Scales (VAS). Mean overall pain as well as mean pain during the best and worst periods were recorded. Forty-six patients were evaluable for efficacy. No significant differences were found between the two treatments. As regards mean worst pain a substantial numerical fall was registered for the treatment group, 21 mm, but the improvement was not significant compared to that of the placebo group. This was probably due to the limited number of patients (the study was prematurely ended due to problems recruiting patients). In conclusion, no significant differences were found between the treatment arm and the controls, in contrast to results from previous studies. Possible explanations are that the doses in this study were generally lower than in previous studies, the mean baseline pain was substantially lower and that the current study was placebocontrolled. Our data indicate that if clodronate is to be used for the alleviation of bone pain in prostate cancer, patients with high baseline should be selected and high intravenous doses should be given at start of the treatment.", "To compare the incidence of palliative response in patients with hormone-resistant prostate cancer (HRPC) treated with mitoxantrone and prednisone (MP) plus clodronate with that of patients treated with MP plus placebo.\n Men with HRPC, bone metastases, and bone pain were randomly assigned to receive clodronate 1,500 mg administered intravenously (IV) or placebo every 3 weeks, in combination with mitoxantrone 12 mg/m2 IV every 3 weeks and prednisone 5 mg orally bid. Patients completed the present pain intensity (PPI) index and Prostate Cancer-Specific Quality-of-Life Instrument at each treatment visit and used a diary to record analgesic use on a daily basis. The primary end point was a reduction to zero or of two points in the PPI or a decrease of 50% in analgesic intake, without increase in either.\n The study accrued 209 eligible patients over 44 months. One hundred sixty patients (77%) had mild PPI scores (1 or 2), and 49 (24%) had moderate PPI scores (3 or 4). The primary end point of palliative response was achieved in 46 (46%) of 104 patients on the clodronate arm and in 41 (39%) of 105 patients on the placebo arm (P =.54). The median duration of response, symptomatic disease progression-free survival, overall survival, and overall quality of life were similar between the arms. Subgroup analysis suggested possible benefit in patients with more severe pain.\n MP provides useful palliation in symptomatic men with HRPC. Clodronate does not increase the rate of palliative response or overall quality of life. Clodronate may be beneficial to patients who have moderate pain, but this requires further confirmation.", "Clodronate relieves bone pain in patients with skeletal metastases. Since the pain relieving mechanism of clodronate may be associated with the antiosteoclastic activity, we have investigated whether the drug has simultaneous actions on bone resorption and pain. Although osteosclerotic metastases are characteristic of prostate carcinoma, bone resorption is also accelerated. The resorbing process can be investigated using a specific immunoassay for ICTP (cross-linked carboxyterminal telopeptide region of type I collagen) which allows the measurement of the degradation of type I collagen in serum samples. We have also determined serum concentration of PICP (carboxyterminal propeptide of type I procollagen) which reflects the synthesis of type I collagen (osteoid). Patients who have relapsed after first-line hormonal therapy, were randomised to receive estramustine phosphate (E) with or without clodronate (C) (E + C, n = 50; E, n = 49). The dose of E was 560 mg and that of C 3.2 g for the first month, thereafter 1.6 g. We saw elevated ICTP and PICP levels in the majority of the patients. A transient decrease in ICTP values occurred simultaneously with pain relief. The changes were more accentuated in the E + C than in the E group but the difference was not significant. In each group serum phosphate concentration decreased markedly (P = 0.001) whereas the activity of alkaline phosphatase remained increased, both indicating a development of osteomalacia during E therapy. The short-term antiosteoclastic effect of C may be explained by the dose reduction, hyperosteoidosis and osteomalacia which inhibit the binding of C on the crystal surfaces and by the late phase of disease.", "Fifty-seven patients with advanced prostate cancer resistant to first-line hormonal therapy were treated with estramustine and additionally randomized for treatment with clodronate or placebo. Clodronate treatment was started with 5 days intravenous administration (300 mg day[-1]) and followed by oral treatment (1.6 g day[-1]) for 12 months. Skeletal pain relief was only about 10% better in the clodronate than in the placebo group. The results do not support the superiority of combined intravenous and oral treatment with clodronate compared with oral administration only." ]

[ "11434406", "7857503", "15708844", "10337446", "9342765", "15605620", "12153829", "10968813", "23196026", "11308434", "10759336", "9342764", "15538592", "12053635", "10823363", "15744631", "12008860", "16555167", "16160619", "16796730", "10591711", "7498868" ]

[ "Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trial.", "Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study.", "Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine.", "Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine.", "Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10.", "Efficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: a double-blind, randomized, placebo-controlled clinical trial.", "Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial.", "Comparison of St John's wort and imipramine for treating depression: randomised controlled trial.", "Clinical significance of hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities.", "Effectiveness of St John's wort in major depression: a randomized controlled trial.", "Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression.", "LI 160, an extract of St. John's wort, versus amitriptyline in mildly to moderately depressed outpatients--a controlled 6-week clinical trial.", "Hypericum extract LI 160 and fluoxetine in mild to moderate depression: a randomized, placebo-controlled multi-center study in outpatients.", "St John's wort or sertraline? Randomized controlled trial in primary care.", "Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study.", "Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline.", "Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression.", "Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study.", "A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder.", "Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298].", "Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks.", "[Treatment of depressive symptoms with a high concentration hypericum preparation. A multicenter placebo-controlled double-blind study]." ]

[ "We have investigated the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS5572 in a double-blind, placebo-controlled multicenter clinical trial. 72 patients (WS 5572: 37, placebo: 35) with a diagnosis of mild to moderate major depressive disorder (according to DSM-IV criteria) were randomized in 42 days of treatment with either 300 mg WS5572 t.i.d. or placebo. The primary efficacy variable was the change of the 17-item Hamilton Depression Scale (HAMD) total score between baseline and double-blind treatment. The study was conducted with an adaptive interim analysis, which led to early stopping because convincing treatment efficacy could already be demonstrated. Group differences in favor of WS 5572 were descriptively apparent as early as day 7 of randomized treatment and were statistically significant at days 28 (p = 0.011) and day 42 (p < 0.001). Between baseline and treatment end, the HAMD total score decreased from 19.7 +/- 3.4 to 8.9 +/- 4.3 points in the Hypericum group and from 20.1 +/- 2.6 to 14.4 +/- 6.8 points in the placebo group (mean +/- SD). Responder rates were consistently higher in the Hypericum group. Comparable group differences in favor of WS 5572 were also found for von Zerssen's Depression Scale (D-S; self-rating), Clinical Global Impressions (CGI) and a global patient's self-assessment (GPA). Tolerability was very good in both groups, with no adverse drug reactions and no clinically relevant changes in safety parameters. The results indicate that Hypericum extract WS 5572 is an effective and well-tolerated drug for the treatment of mild to moderate major depressive disorder.", "A randomized, double-blind study examining the effectiveness and tolerance of a standardized hypericum preparation when compared to maprotiline was performed in a group of 102 patients with depression, in accordance with ICD-10, F 32.1. The study was conducted in the offices of neurology and psychiatry specialists. The patients received, over a period of 4 weeks, either 3 x 300 mg of the hypericum extract or 3 x 25 mg maprotiline pills of identical appearance. Effectiveness was determined using the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S), and the Clinical Global Impression Scale (CGI). The total score of the HAMD scale dropped during the 4 weeks of therapy in both treatment groups by about 50%. The mean values of the D-S scale and the CGI scale showed similar results, and after 4 weeks of therapy, no significant differences in either treatment group were noticed. The onset of the effects occurred up to the second week of treatment, but were observed earlier with maprotiline than with the hypericum extract. On the other hand, maprotiline treatment resulted in more cases of tiredness, mouth dryness, and heart complaints.", "To investigate the efficacy of hypericum extract WS 5570 (St John's wort) compared with paroxetine in patients with moderate to severe major depression.\n Randomised double blind, double dummy, reference controlled, multicentre non-inferiority trial.\n 21 psychiatric primary care practices in Germany.\n 251 adult outpatients with acute major depression with total score > or = 22 on the 17 item Hamilton depression scale.\n 900 mg/day hypericum extract WS 5570 three times a day or 20 mg paroxetine once a day for six weeks. In initial non-responders doses were increased to 1800 mg/day hypericum or 40 mg/day paroxetine after two weeks.\n Change in score on Hamilton depression scale from baseline to day 42 (primary outcome). Secondary measures were change in scores on Montgomery-Asberg depression rating scale, clinical global impressions, and Beck depression inventory.\n The Hamilton depression total score decreased by mean 14.4 (SD 8.8) points, corresponding to 56.6% (SD 34.3%) of the baseline value, in the hypericum group and by 11.4 (SD 8.6) points (44.8% (SD 33.5%) of baseline value) in the paroxetine group (intention to treat analysis; similar results were observed in the per protocol analysis). The intention to treat analysis (lower one sided 97.5% confidence limit 1.5 points for the difference hypericum minus paroxetine) and the per protocol analysis (lower confidence limit 0.7 points) showed non-inferiority of hypericum and statistical superiority over paroxetine. The lower limits in both cases exceeded the pre-specified non-inferiority margin of -2.5 points and the superiority margin of 0. The incidence of adverse events was 0.035 and 0.060 events per day of exposure for hypericum and paroxetine, respectively.\n In the treatment of moderate to severe major depression, hypericum extract WS 5570 is at least as effective as paroxetine and is better tolerated.", "In a randomised double-blind comparative trial, the antidepressant efficacy of a daily dose of 800 mg of the St. John's wort extract LoHyp-57 (dry extract of St. John's wort, drug extrakt ratio 5-7:1, solvent, ethanol 60% [w/w]) was shown to be equivalent to that of 20 mg fluoxetine (CAS 54910-89-3) in elderly patients with mild or moderate depressive episodes according to ICD 10 (International Statistical Classification of Diseases and Related Health Problems). Treatment was given for six weeks. 149 out-patients (129 females and 20 males) were included in the intention-to-treat analysis. 72 of these patients were assigned to the ICD 10 diagnostic criterion F32.0 (mild depressive episode), while 77 patients were suffering from moderate depressive episodes, corresponding to F32.1. The principal target criterion was the patient's global score on the HAMILTON Depression Scale (items 1-17). During the six-week course of treatment with LoHyp-57, the HAMILTON global score fell from 16.60 points at entry to 7.91 points, and in the fluoxetine sample it fell from 17.18 to 8.11 points. In the group of patients with mild depressive episodes, the score showed a mean fall from 14.21 to 6.21 points on LoHyp-57, and from 15.21 to 7.46 points on fluoxetine. In patients with moderate depressive episodes, the score showed a mean fall from 18.73 to 9.43 points on LoHyp-57 and from 19.10 to 8.75 points on fluoxetine. The efficacy of both medications was found to be equivalent both in mild and moderate depressive episodes. Both treatment groups showed adverse drug reactions (ADRs). Twelve ADRs with a possible relationship to the study medication were reported during treatment with LoHyp-57. Six patients were prematurely withdrawn from treatment with the study medication for this reason. On fluoxetine 17 ADRs occurred with a possible relationship to the study medication. These led to abandonment of treatment and therefore premature withdrawal from the study in 8 cases.", "The special extract of St. John's wort, LI 160, exhibited a superior antidepressant efficacy compared to placebo in several controlled trials. Two further trials demonstrated a similar reduction of depressive symptomatology under LI 160 compared to tricyclics. All these trials were performed in mildly to moderately depressed patients. The present investigation was a randomized, controlled, multicentre, 6-week trial comparing 1800 mg LI 160/die to 150 mg imipramine/die in severely depressed patients according to ICD-10. The main efficacy parameter, a reduction of the total score of the Hamilton Depression Scale, proved both treatment regimens very effective at the end of the 6 week treatment period (mean values 25.3 to 14.5 in the LI 160 group and 26.1 to 13.6 in the imipramine group), but not statistically equivalent within a a-priori defined 25% interval of deviation. The analysis of subgroups with more than a 33% and 50% reduction of the HAMD total score justified the assumption of equivalence within a 25% deviation interval. This view was also supported by the global efficacy ratings from patients and investigators. Regarding adverse events, the nonrejection of the nonequivalence hypothesis denotes a superiority of the herbal antidepressant. These main result indicate that LI 160 might be a treatment alternative to the synthetic tricyclic antidepressant imipramine in the majority of severe forms of depressions. However, more studies of this type must be performed before a stronger recommendation can be made.", "In this double-blind, randomized, placebo-controlled, prospective study, the clinical efficacy and tolerability of oral Hypericum extract STW 3-VI (Laif) 900 mg once daily was compared with that of placebo. A total of 140 outpatients (94 women; 46 men) with moderate depressive disorders and a 17-item Hamilton Depression Scale (HAMD-17) score of 20 to 24 were enrolled in this study. Following a single-blind placebo run-in period of 7 days, the patients were randomized to Hypericum extract 900 mg or placebo for the 6-week treatment period. Nineteen patients have been excluded from the per protocol collective because of violations of protocol regarding the scheduling of study visits and intake of study medication. The primary endpoint for treatment efficacy was the change in total HAMD-17 score at the end of the 6-week treatment period. The HAMD-17 total score decreased significantly from baseline by approximately 11.1 +/- 4.5 points (from 22.8 +/- 1.1 to 11.8 +/- 4.4) in the Hypericum group and by approximately 3.4 +/- 3.9 points (from 22.6 +/- 1.2 to 19.2 +/- 3.8) in the placebo group (P < .001). Comparable group differences in favor of Hypericum were revealed by an additional responder analysis, the von Zerssen's Adjective Mood Scale, the Clinical Global Impressions scale, and a global efficacy assessment. Tolerability was very good in both groups; neither serious adverse events nor clinically relevant changes in safety parameters were observed, and only 2 cases demonstrated a possible connection between an adverse event and the study medication. The final safety assessment showed no differences between the Hypericum extract and placebo groups. The study provided evidence that Hypericum extract STW 3-VI in a once-daily dosing regimen may be an effective and well-tolerated option for patients with moderate depressive disorders.", "In a double-blind, randomized, placebo-controlled trial with 375 patients the authors investigated the antidepressant efficacy and safety of 300 mg t.i.d. of hydroalcoholic Hypericum perforatum extract WS 5570.\n The study participants were male and female adult outpatients with mild to moderate major depression (single or recurrent episode, DSM-IV criteria). After a single-blind placebo run-in phase, the patients were randomly assigned, 186 to WS 5570 and 189 to placebo, after which they received double-blind treatment for 6 weeks. Follow-up visits were held after 1, 2, 4, and 6 weeks. The primary outcome measure was the change from baseline in the total score on the 17-item Hamilton Depression Rating Scale. In addition, analyses of responders (patients with at least a 50% reduction in Hamilton total score) and patients with remissions (patients with a total score of 6 or less on the Hamilton scale at treatment end) were carried out, and subscale/subgroup analyses were conducted. The design included an adaptive interim analysis performed after random assignment of 169 patients with options for group size adjustment or early termination.\n Compared to placebo, WS 5570 produced a significantly greater reduction in total score on the Hamilton depression scale and significantly more patients with treatment response or remission. It was more effective in patients with higher baseline Hamilton scores and led to global reduction of depression-related core symptoms, assessed with the melancholia subscale of the Hamilton scale. The placebo and WS 5570 groups had comparable adverse events.\n H. perforatum extract WS 5570 was found to be safe and more effective than placebo for the treatment of mild to moderate depression.", "To compare the efficacy and tolerability of Hypericum perforatum (St John's wort extract) with imipramine in patients with mild to moderate depression.\n Randomised, multicentre, double blind, parallel group trial.\n 40 outpatient clinics in Germany. Participants: 324 outpatients with mild to moderate depression.\n 75 mg imipramine twice daily or 250 mg hypericum extract ZE 117 twice daily for 6 weeks.\n Hamilton depression rating scale, clinical global impression scale, and patient's global impression scale.\n Among the 157 participants taking hypericum mean scores on the Hamilton depression scale decreased from 22.4 at baseline to 12.00 at end point; among the 167 participants taking imipramine they fell from 22.1 to 12.75. Mean clinical global impression scores at end point were 2.22 out of 7 for the hypericum group and 2.42 for the imipramine group. On the 7 point self assessments of global improvement completed by participants (score of 1 indicating \"very much improved\" and 7 indicating \"very much deteriorated\") mean scores were 2.44 in the hypericum group and 2.60 in the imipramine group. None of the differences between treatment groups were significant. However, the mean score on the anxiety-somatisation subscale of the Hamilton scale (3.79 in the hypericum group and 4.26 in the imipramine group) indicated a significant advantage for hypericum relative to imipramine. Mean scores on the 5 point scale used by participants to assess tolerability (score of 1 indicating excellent tolerability and 5 indicating very poor tolerability) were better for hypericum (1.67) than imipramine (2.35). Adverse events occurred in 62/157 (39%) participants taking hypericum and in 105/167 (63%) taking imipramine. 4 (3%) participants taking hypericum withdrew because of adverse events compared with 26 (16%) taking imipramine.\n This Hypericum perforatum extract is therapeutically equivalent to imipramine in treating mild to moderate depression, but patients tolerate hypericum better.", "In a randomized, double-blind, placebo-controlled, multicenter study, the clinical efficacy and safety of two different extracts of St. John's wort were investigated in 147 male and female out-patients suffering from mild or moderate depression according to DSM-IV criteria. Fifty-six (38.1%) of them had an initial total score ≥ 22 points on the Hamilton Rating Scale for Depression (HAMD, 17-item version). Following a placebo run-in period of three to seven days, the patients were randomized to one of three treatment groups: During the 42-day treatment period, they received 3×1 tablet of either placebo, Hypericum extract WS 5573 (300mg, with a content of 0.5% hyperforin), or Hypericum extract WS 5572 (300 mg, with a content of 5% hyperforin). The manufacturing process for both Hypericum preparations was identical, they only differed with regard to their content of hyperforin. Efficacy regarding depressive symptoms was assessed on days 0, 7,14,28, and 42. The last observation of patients withdrawn from the trial prematurely was carried forward. At the end of the treatment period (day 42), the patients receiving WS 5572 (5% hyperforin) exhibited the largest HAMD reduction versus day 0 (10.3 ± 4.6 points; mean ± SD), followed by the WS 5573 group (0.5% hyperforin; HAMD reduction 8.5 ± 6.1 points) and the placebo group (7.9 ± 5.2 points). The monotonie trend was significant (Jonckheere-Terpstra test; p = 0.017). In patients with an initial HAMD total score ≥ 22, the HAMD reduction was even by 16.5% larger than in the total study group receiving WS 5572. More severely depressed patients treated with WS 5573, however, showed a 22.4% lower reduction of the HAMD total score than the entire WS 5573 treatment group. In patients with HAMD ≥ 22, WS 5572 showed a 53.8% larger HAMD reduction than placebo, whereas WS 5573 was not relevantly different from the placebo level. The mean HAMD reductions, treatment end versus baseline, for the more severely depressed patients were 12.0 (3.7) points, 6.6 (7.7) points and 7.8 (5.4) points [mean (SD)] for WS 5S72, WS 5573 and placebo, respectively. The results of a responder analysis support these findings. The data point to a dose-response relationship between the antidepressant efficacy of Hypericum extract and its hyperforin content. The extract with a higher content of hyperforin was particularly effective in patients who were more severely depressed.\n Copyright © 1998 Gustav Fischer Verlag. Published by Elsevier GmbH.. All rights reserved.", "Extracts of St John's wort are widely used to treat depression. Although more than 2 dozen clinical trials have been conducted with St John's wort, most have significant flaws in design and do not enable meaningful interpretation.\n To compare the efficacy and safety of a standardized extract of St John's wort with placebo in outpatients with major depression.\n Randomized, double-blind, placebo-controlled clinical trial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States.\n Two hundred adult outpatients (mean age, 42.4 years; 67.0% female; 85.9% white) diagnosed as having major depression and having a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 20.\n Participants completed a 1-week, single-blind run-in of placebo, then were randomly assigned to receive either St John's wort extract (n = 98; 900 mg/d for 4 weeks, increased to 1200 mg/d in the absence of an adequate response thereafter) or placebo (n = 102) for 8 weeks.\n The primary outcome measure was rate of change on the HAM-D over the treatment period. Secondary measures included the Beck Depression Inventory (BDI), Hamilton Rating Scale for Anxiety (HAM-A), the Global Assessment of Function (GAF) scale, and the Clinical Global Impression-Severity and -Improvement scales (CGI-S and CGI-I).\n The random coefficient analyses for the HAM-D, HAM-A, CGI-S, and CGI-I all showed significant effects for time but not for treatment or time-by-treatment interaction (for HAM-D scores, P<.001, P =.16, and P =.58, respectively). Analysis of covariance showed nonsignificant effects for BDI and GAF scores. The proportion of participants achieving an a priori definition of response did not differ between groups. The number reaching remission of illness was significantly higher with St John's wort than with placebo (P =.02), but the rates were very low in the full intention-to-treat analysis (14/98 [14.3%] vs 5/102 [4.9%], respectively). St John's wort was safe and well tolerated. Headache was the only adverse event that occurred with greater frequency with St John's wort than placebo (39/95 [41%] vs 25/100 [25%], respectively).\n In this study, St John's wort was not effective for treatment of major depression.", "Treatment with St John's wort extract tablets (hypericum Ze 117) and the commonly used slow serotonin reuptake inhibitor (SSRI) fluoxetine was compared in patients with mild-moderate depression with entry Hamilton Depression Scale (HAM-D) (21-item) in the range 16-24, in a randomized, double-blind, parallel group comparison in 240 subjects; fluoxetine: 114 (48%), hypericum: 126 (52%). After 6 weeks' treatment, mean HAM-D at endpoint decreased to 11.54 on hypericum and to 12.20 on fluoxetine (P < 0.09), while mean Clinical Global Impression (CGI) item I (severity) was significantly (P < 0.03) superior on hypericum, as was the responder rate (P = 0.005). Hypericum safety was substantially superior to fluoxetine, with the incidence of adverse events being 23% on fluoxetine and 8% on hypericum. The commonest events on fluoxetine were agitation (8%), GI disturbances (6%), retching (4%), dizziness (4%), tiredness, anxiety/nervousness and erectile dysfunction (3% each), while on hypericum only GI disturbances (5%) had an incidence greater than 2%. We concluded that hypericum and fluoxetine are equipotent with respect to all main parameters used to investigate antidepressants in this population. Although hypericum may be superior in improving the responder rate, the main difference between the two treatments is safety. Hypericum was superior to fluoxetine in overall incidence of side-effects, number of patients with side-effects and the type of side-effect reported.", "Up to now, the antidepressant efficacy of the extract of St. John's wort, LI 160, has been compared to imipramine and maprotiline, demonstrating similar antidepressant efficacy in mildly to moderately depressed patients, treated either with LI 160 or the respective synthetic comparator. In the study reported here, LI 160 (total daily dose: 900 mg) was compared with the sedating tricyclic amitriptyline (total daily dose: 75 mg) in a controlled, randomized, multicentre trial. At the end of the 6-week study, the major target variable, the Hamilton Depression Scale response rate, exhibited no statistically significant difference between the groups, although a tendency for a better response rate was seen in the amitriptyline group. The secondary efficacy parameters, decreases in the total Hamilton Depression and Montgomery-Asberg scores, showed a significant advantage for amitriptyline, but only at week 6. With regard to tolerability, LI 160 was clearly superior to amitriptyline, particularly in relation to anticholinergic and Central Nervous System adverse events. Thus, 37% of the LI 160 treated patients reported adverse events, compared to 64% in the amitriptyline group. This considerable superiority in tolerability for LI 160 in relation to amitriptyline, could confer an advantage in improving compliance for antidepressant pharmacotherapy.", "Efficacy and tolerability of Hypericum LI 160 was compared to fluoxetine and placebo in mild to moderate Major Depression (DSM-IV) in a 4-week randomized, double-blind trial. One hundred and sixty-three outpatients from 15 general practitioner centers received either 900 mg Hypericum LI 160, 20 mg fluoxetine, or placebo daily. Amelioration was measured by the Hamilton and the Montgomery-Asberg Depression scales. Response and remission rates and global ratings by investigators and patients were measured. Adverse event reports, laboratory screening, vital signs, physical exams and ECG were collected. No significant differences could be observed regarding efficacy measures except for remission rate (Hypericum 24%; fluoxetine 28%; placebo 7 %). Hypericum was significantly better tolerated than fluoxetine. Hypericum LI 160 or fluoxetine were not more effective in short-term treatment in mild to moderate depression than placebo.", "To compare the change in severity of depressive symptoms and occurrence of side effects in primary care patients treated with St John's wort (SJW) and sertraline.\n Double-blind, randomized 12-week trial.\n Community-based offices of 12 family physicians practising in greater Montreal, Que.\n Eighty-seven men and women with major depression and an initial score of > or = 16 on the Hamilton Rating Scale for Depression (Ham-D).\n Patients were randomized to treatment with either sertraline (50 to 100 mg/d) or SJW (900 to 1800 mg/d) in a double-blind fashion. Assessment of depression was done at entry and at 2, 4, 8, and 12 weeks using the Ham-D, the Beck Depression Inventory (BDI), and a questionnaire asking about compliance and side effects.\n Changes from baseline in Ham-D and BDI scores and self-reported side effects.\n There were no important differences in changes in mean Ham-D and BDI scores (using intention-to-treat analysis), with and without adjustment for baseline demographic characteristics, between the two groups at 12 weeks. Significantly more side effects were reported in the sertraline group than in the SJW group at 2 and 4 weeks' follow up.\n The more benign side effects of SJW make it a good first choice for this patient population.", "Hypericum (St. John's wort) has been shown to be as efficacious and well tolerated as standard antidepressants in the treatment of depression but has not been compared with selective serotonin reuptake inhibitors (SSRIs).\n This study compared hypericum and the SSRI sertraline in the treatment of depression.\n In a double-blind, randomized study conducted in a community hospital, 30 male and female outpatients (19 women, 11 men; mean age, 45.5 years) with mild to moderate depression received 600 mg/d of a standardized extract of hypericum (LI 160) or 50 mg/d sertraline for I week, followed by hypericum 900 mg/d or sertraline 75 mg/d for 6 weeks.\n The severity of symptoms, as assessed by scores on the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression scale, was significantly reduced in both treatment groups (P < 0.01). Clinical response (defined as a > or =50% reduction in HAM-D scores) was noted in 47% of patients receiving hypericum and 40% of those receiving sertraline. The difference was not statistically significant. Both agents were well tolerated. A post hoc power analysis indicated that failure to reach statistical significance between treatments resulted primarily from an absence of clinical differences rather than the small sample size.\n The hypericum extract was at least as effective as sertraline in the treatment of mild to moderate depression in a small group of outpatients.", "The objective of this double-blind, multi-center clinical study was to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression.\n A total of 241 patients with a diagnosis of moderate depressive disorder (according to ICD-10 criteria) were randomized with either 50 mg sertraline or 612 mg hypericum extract (hypericum group n = 123; sertraline group n = 118). According to the study protocol, 200 patients were treated for at least 12 weeks ( n = 102 hypericum extract; n = 98 sertraline); 81 patients in the hypericum group and 80 in the sertraline group were treated after week 12 for an additional 12 weeks. Thus, most patients were treated for a period of 6 months. The primary efficacy variable was the 17-item HAMD total score at the end of the first 12-week double-blind treatment period.\n After the first 12-week treatment period, the HAMD score decreased from almost identical initial values (22.0 +/- 1.1 for hypericum and 22.1 +/- 1.1 points for sertraline) to 8.3 +/- 5.5 points (hypericum) and 8.1 +/- 5.6 points (sertraline) (mean +/- SD) in the patients treated per-protocol (PP) population. The statistical test for non-inferiority (boundary delta = 3) revealed that hypericum extract is not inferior to sertraline ( P < 0.0001). The mean difference between the treatments was 0.1995 points, with a corresponding one-sided 97.5 % confidence interval (-infinity, 1.3772). In patients who continued treatment in the follow-up phase, the HAMD score at the end of the study was 5.7 +/- 4.8 points (hypericum group) and 7.1 +/- 6.3 points (sertraline group). Comparable improvement was also found for the von Zerssen's Adjective Mood Scale (BfS) and CGI during the first and second 12-week treatment period in both treatment groups. With 68.6 % of patients in the hypericum group and 70.4 % in the sertraline group, the percentage of patients rated as responders did not differ significantly between treatment groups (12 weeks). The adverse events of 12 patients in the hypericum group (9.8 %) and of 16 patients in the sertraline group (13.6 %) were possibly related to study medication. No basic differences in the treatment groups were observed and no interaction with concomitant medication was documented. In most cases , the investigators assessed the tolerability of hypericum extract and sertraline as \"good\" or \"very good.\"\n The results indicate that hypericum extract STW 3 is not inferior to sertraline and that it is a well-tolerated drug for the treatment of moderate depression. These favorable effects were achieved with a once-daily dose of 612 mg of hypericum extract given for up to 24 weeks.", "In a randomized, controlled, double-blind trial, 70 patients (mean age, 49.7 years) suffering from mild to moderate depression received one tablet of either St. John's Wort (Hypericum perforatum) extract (Calmigen) or fluoxetine hydrochloride (Prozac) twice a day for 6 weeks. Efficacy was determined according to the 17-item Hamilton Rating Scale for Depression (HAMD), the von Zerssen depression scale (DS), Clinical Global Impression (CGI), and patients' overall evaluation. Significant decreases (P<.001) of 50% in the Hypericum group and 58% in the fluoxetine group in the HAMD score and of 42% and 52% on the DS spoke to the efficacy of both medications. The Hypericum extract achieved 83% of the efficacy of fluoxetine on the HAMD and 78% on the DS. Assessments by physicians (CGI) and patients indicated considerable improvement with no between-treatment differences. Of the 9 dropouts (13%), 2 in the Hypericum group and 2 in the fluoxetine group were due to adverse reactions. Safety evaluations demonstrated only minor changes. The Hypericum preparation tested in this study is therapeutically equivalent to fluoxetine and is therefore a rational alternative to synthetic antidepressants.", "The objective of this double-blind, randomised, placebo-controlled, multicentre clinical study was to demonstrate the non-inferiority and safety of the hypericum extract STW3-VI in a once-daily dosage regime in the treatment of moderate depression. During the 6-week treatment phase, the course of depression was documented by use of HAMD (items 1-17), the von Zerssen's Adjective Mood Scale (BfS) and the CGI scales. The primary objective of this 3-arm design study was to demonstrate the non-inferiority of hypericum extract STW3-VI (900 mg) to the SSRI citalopram (20 mg) and superiority of hypericum over placebo.\n Outpatients (N = 388) suffering from moderate depression were enrolled. The safety and tolerability of hypericum extract in comparison to citalopram and placebo was investigated on the basis of CGI, the occurrence of adverse events and the investigation of laboratory parameters and vital signs.\n From almost identical baseline values of 21.9 +/- 1.2 points (hypericum extract), 21.8 +/- 1.2 points (citalopram) and 22.0 +/- 1.2 points (placebo), the HAMD score was reduced to 10.3 +/- 6.4 (hypericum extract), 10.3 +/- 6.4 (citalopram) and 13.0 +/- 6.9 (placebo), respectively. Based on this data, the statistical significant therapeutic equivalence of hypericum extract STW3-VI to citalopram (p < 0.0001) and the superiority of this hypericum extract over placebo (p < 0.0001) was demonstrated. At the end of treatment 54.2 % (hypericum extract), 55.9 % (citalopram) and 39.2 % (placebo) of the patients were assessed as therapy responders. The secondary efficacy parameters, change in BfS, CGI and amount of therapy responders showed that the hypericum group was not statistically different from the citalopram group, and significantly superior to the placebo group. Significantly more adverse events with \"certain\", \"probable\" or \"possible\" relation to study medication were documented in the citalopram group (hypericum: 17.2 %, citalopram: 53.2 %, placebo: 30 %). In most cases, the investigators assessed the tolerability of hypericum extract, citalopram and placebo as \"good\" or \"very good\".\n The non-inferiority of hypericum extract as compared to citalopram and the superiority of both active compounds to placebo were demonstrated, as well as a better safety and tolerability of hypericum extract in comparison to citalopram. These results revealed that hypericum extract STW3-VI is a good alternative to chemically defined antidepressants in the treatment of outpatients with moderate depression.", "This study looks to compare the antidepressant efficacy and safety of a standardized extract of St John's wort with both placebo and fluoxetine.\n After a 1-week single-blind washout, patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized to 12 weeks of double-blind treatment with LI-160 St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was the primary efficacy measure, and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups, treating the baseline HAMD-17 as the covariate.\n One hundred thirty-five patients (57% women; mean age, 37.3 +/- 11.0; mean HAMD-17, 19.7 +/- 3.2) were randomized to double-blind treatment and were included in the intent-to-treat analyses. Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John's wort group (n = 45; mean +/- SD, 10.2 +/- 6.6) compared with the fluoxetine group (n = 47; 13.3 +/- 7.3; P < 0.03) and a trend toward a similar finding relative to the placebo group (n = 43; 12.6 +/- 6.4; P = 0.096). There was also a trend toward higher rates of remission (HAMD-17 <8) in the St John's wort group (38%) compared with the fluoxetine group (30%) and the placebo group (21%). Overall, St John's wort appeared to be safe and well tolerated.\n St John's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. A (25%) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage (indicating a moderate effect size, d = 0.45) of St John's wort over placebo.", "The aim of the current study was to assess the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS 5570 at doses of 600 mg/day in a single dose and 1200 mg/day in two doses.\n The participants in this double-blind, randomized, placebo-controlled, multi-center clinical trial were male and female adult out-patients with an episode of mild or moderate major depressive episode (single or recurrent episode, DSM-IV criteria). As specified by the relevant guideline, the study was preceded by a medication-free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to WS 5570 600 mg/day, 127 to WS 5570 1200 mg/day, and 82 to placebo. The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression (HAM-D, 17-item version) between baseline and endpoint. Additional measures included the number of responders, the number of patients in remission, and several other standard rating scales. Efficacy and safety were assessed after 2 and 6 weeks. The design included an interim analysis performed after randomization with the option of early termination.\n After 6 weeks of treatment, mean +/- standard deviation decreases in HAM-D total scores of 11.6 +/- 6.4, 10.8 +/- 7.3, and 6.0 +/- 8.1 points were observed for the WS 5570 600 mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis). Secondary measures of treatment efficacy also showed that both WS 5570 groups were statistically superior to placebo. Significantly more patients in the WS 5570 treatment groups than in the placebo group showed treatment response and remission. WS 5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment. The number of patients who experienced remission was higher in the WS 5570 1200 mg/day group than the WS 5570 600 mg/day group. The incidence of adverse events was low in all groups. The adverse event profile was consistent with the known profile for Hypericum extract preparations.\n Hypericum perforatum extract WS 5570 at doses of 600 mg/day (once daily) and 1200 mg/day (600 mg twice daily) were found to be safe and more effective than placebo, with comparable efficacy of the WS 5570 groups for the treatment of mild to moderate major depression.", "To assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression.\n Randomised, double blind, multicentre, parallel group trial for 8 weeks.\n Trained panel of 18 general practitioners from four German states: Bavaria, Berlin, Rhineland Palatinate, and Saxony.\n 263 patients (66 men, 197 women) with moderate depression according to ICD-10 (international classification of diseases, 10th revision) codes F32. 1 and F33.1.\n 1050 mg hypericum extract (350 mg three times daily), 100 mg imipramine (50 mg, 25 mg, and 25 mg daily), or placebo three times daily.\n Change from baseline score on the 17 item version of the Hamilton depression scale, the Hamilton anxiety scale, the clinical global impressions scale, Zung's self rating depression scale, and SF-36, and adverse events profile.\n Hypericum extract was more effective at reducing Hamilton depression scores than placebo and as effective as imipramine (mean -15.4 (SD 8.1), -12.1 (7.4), and -14.2 (7.3) respectively). Comparable results were found for Hamilton anxiety and clinical global impressions scales and were most pronounced for the Zung self rating depression scale. Quality of life was more improved in the standardised mental component scale of the SF-36 with both active treatments than with placebo but in the physical component scale was improved only by hypericum extract compared with placebo. The rate of adverse events with hypericum extract was in the range of the placebo group but lower than that of the imipramine group (0.5, 0.6, and 1.2 events per patient respectively).\n At an average dose of 350 mg three times daily hypericum extract was more effective than placebo and at least as effective as 100 mg imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life.", "In a multicenter, placebo-controlled double-blind trial, the effect on depression (ICD 10 F 32.1) of treatment with an innovative highly concentrated hypericum preparation was investigated. The study contained 97 outpatients who received 100 to 120 mg of the hypericum extract bid. The course of the illness was assessed with the Hamilton Depression Scale (HAMD), the von Zerssen Depressivity Scale (D-S) and the Clinical Global Impression Scale (CGIS). Treatment resulted in an appreciable improvement in the symptoms of depression, and the 70% response rate (n = 43), corresponded to that of chemical antidepressants. The preparation also showed an anxiolytic effect. The substance was extremely well tolerated, and no side-effects were reported by any of the patients." ]

[ "8351363", "11719664", "9171752", "1913123", "1994402" ]

[ "Intraarterial thrombolysis of lower extremity occlusions: prospective, randomized comparison of forced periodic infusion and conventional slow continuous infusion.", "Peripheral artery occlusion: treatment with abciximab plus urokinase versus with urokinase alone--a randomized pilot trial (the PROMPT Study). Platelet Receptor Antibodies in Order to Manage Peripheral Artery Thrombosis.", "Prospective randomized trial of high-dose bolus versus low-dose tissue plasminogen activator infusion in the management of acute limb ischaemia. Thrombolysis Study Group.", "Randomized trial of intra-arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra-arterial streptokinase in peripheral arterial thrombolysis.", "Two urokinase dose regimens in native arterial and graft occlusions: initial results of a prospective, randomized clinical trial." ]

[ "A prospective randomized controlled trial compared forced infusion (FI) of urokinase (UK) with conventional slow continuous infusion (CI) in 25 patients with 25 acutely ischemic lower limbs. Demographics, ischemia categories, and infusion rates and doses were similar for both groups. A preliminary single-pass bolus of UK was injected into the thrombus in all patients with a pulsed-spray technique, and heparin was administered. UK was then infused with a CI pump (n = 13) or a prototype pulsed-spray pump (n = 12). The primary end point was patency, defined as at least 95% thrombolysis by volume, with brisk antegrade flow occurring within 4 hours. Eleven of the 12 patients (92%) who underwent FI and nine of the 13 (70%) who underwent CI had patency within 4 hours. However, 10 patients who underwent FI and nine who underwent CI had residual thrombi prolonging infusion. No significant differences between the two groups were apparent in speed of lysis, initial success rates, complication rates, or 30-day clinical outcome. Lytic therapy, however, was completed within 24 hours in 18 of 23 (78%) successfully treated patients (P = .01).", "To evaluate the combination of a platelet glycoprotein IIb/IIIa complex receptor inhibitor and urokinase for treatment of recent (<or=6 weeks) arterial occlusion of the legs.\n Seventy patients with lower extremity arterial occlusion of less than 6 weeks duration were randomly separated into two treatment groups: urokinase plus abciximab or urokinase plus placebo. Primary end points were the rate of major complications at 30 days after randomization and the rates of amputation-free survival and survival without open surgery or major amputation at follow-up of 90 days. Two readers unaware of the patients' treatment group assignments analyzed digital subtraction angiograms as they related to the study end points, with a final consensus reading.\n Thrombolysis relative to clot length was faster in the urokinase-plus-abciximab group (odds ratio, 0.52; 95% CI: 0.35, 0.76; P < .001). There were no procedure-related deaths or intracranial hemorrhages, but the rate of nonfatal major bleeding was higher with urokinase plus abciximab (four of 50 patients) than with urokinase alone (none of 20 patients; P = .32). At 90 days, amputation-free survival was 96% (48 of 50 patients) in the urokinase-plus-abciximab group compared with 80% (16 of 20 patients) in the urokinase alone group. The hazard ratio for the two Kaplan-Meier curves was 0.42 (95% CI: 0.16, 0.96; P = .04).\n In patients with lower extremity arterial occlusion who were undergoing urokinase thrombolysis, adjunctive abciximab treatment resulted in faster thrombus dissolution and improved amputation-free survival, despite an increase in major bleeding.", "Accelerated thrombolysis with high-dose bolus tissue plasminogen activator (tPA) may enable patients with more severe acute leg ischaemia to be treated without recourse to surgery. This study was a randomized comparison of two thrombolytic regimens.\n One hundred patients with acute leg ischaemia of less than 30 days' duration were randomized to receive either high-dose bolus tPA (three doses of 5 mg over 30 min, then 3.5 mg/h for up to 4 h, then 0.5-1.0 mg/h) or conventional low-dose tPA (0.5-1.0 mg/h). The groups were well matched for age, cardiovascular risk factors, duration and severity of ischaemia, site, cause and length of arterial occlusion.\n The median duration of infusion in the high-dose group was 4.0 (range 0.25-46) h compared with 20 (range 2-46) h for low-dose infusion (P < 0.0001). Successful thrombolysis was achieved in 45 of 49 high-dose and 39 of 44 low-dose infusions but significantly more adjunctive procedures were required following high-dose bolus infusion (26 versus 16 patients) (P = 0.002). Thirty days after treatment was commenced, limb salvage was achieved in 39 of 49 patients in the high-dose group compared with 37 of 44 who had a low-dose infusion of tPA. Six and two patients respectively required amputation. Four patients in the high-dose group and five in the low-dose group died. Three patients in each group suffered a major haemorrhage and one in the low-dose group had a stroke.\n High-dose bolus therapy significantly accelerated thrombolysis with tPA without compromising outcome. Some 50 per cent of patients were treated within 4 h enabling thrombolysis to be used as primary therapy for patients with acute critical ischaemia.", "Sixty patients were recruited into a randomized parallel group comparison of three thrombolytic regimens for acute or subacute peripheral arterial thrombosis. There were no significant differences in age, duration of history, length of occlusion or presence of neurosensory deficit between the groups. Initially successful lysis was significantly greater with intra-arterial (IA) recombinant tissue plasminogen activator (rt-PA) than with either streptokinase (Sk) (P less than 0.04) or intravenous (IV) rt-PA (P less than 0.01). The duration of therapy varied from a median of 35 h with IA rt-PA to 40 h with Sk (P greater than 0.5). The median (confidence interval) increase in ankle:brachial pressure index following IA rt-PA of 0.57 (0.33-0.82) was significantly higher than for either Sk of 0.24 (0-0.57) or for IV rt-PA of 0.18 (0-0.41). Limb salvage at 30 days was achieved in 80, 60 and 45 per cent respectively for IA rt-PA, Sk and IV rt-PA. Haemorrhagic complications occurred in six patients following Sk and in 13 following IV rt-PA; only one minor haemorrhage occurred following a catheter perforation in a patient who received IA rt-PA (P less than 0.05). IA rt-PA provides a more effective, safer fibrinolytic regimen than conventional therapy with Sk. IV rt-PA has not been as successful and carries a significantly higher risk of haemorrhagic complications.", "The effects of two urokinase (UK) dose regimens on lysis time, lytic success, primary clinical success, and frequency of complications of peripheral thrombolysis were compared. Seventy-two intraarterial UK infusions were performed by means of standard catheter-directed infusion techniques in 63 patients with symptomatic peripheral arterial or bypass graft occlusions. Patients were prospectively randomized to high-dose (250,000 U/h for 4 hours and then 125,000 U/h) or low-dose (50,000 U/h) regimens. The mean time to complete lysis was 20.8, 26.0, 16.5, and 18.2 hours for the high-dose artery, low-dose artery, high-dose graft, and low-dose graft groups, respectively (P was not significant). Respective mean infusion durations were 27.1, 35.4, 22.2, and 25.3 hours. Clinical success was achieved in 65%-85% of cases. The frequency of complications was equivalent between groups, except for a higher frequency of minor bleeding complications in the high-dose group. The two urokinase dose regimens studied were equally effective in enabling peripheral thrombolysis." ]

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[ "Reversal of anemia by erythropoietin therapy retards the progression of chronic renal failure, especially in nondiabetic patients.", "Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy.", "Recombinant human erythropoietin treatment in pre-dialysis patients. A double-blind placebo-controlled trial.", "Early intervention with recombinant human erythropoietin therapy.", "Analysis of heart morphology and function following erythropoietin treatment of anemic dialysis patients.", "Effects of normal hematocrit on ambulatory blood pressure in epoetin-treated hemodialysis patients with cardiac disease.", "Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial.", "Effect of erythropoietin treatment on physical exercise capacity and on renal function in predialytic uremic patients.", "Double-blind comparison of full and partial anemia correction in incident hemodialysis patients without symptomatic heart disease.", "Health-related quality of life associated with recombinant human erythropoietin therapy for predialysis chronic renal disease patients.", "Morbidity and mortality in hemodialysis patients with and without erythropoietin treatment: a controlled study.", "Non-cardiac benefits of human recombinant erythropoietin in end stage renal failure and anaemia.", "Treatment of the anemia of chronic renal failure with subcutaneous recombinant human erythropoietin.", "Safety and efficacy of erythropoietin in children with chronic renal failure.", "Canadian randomized trial of hemoglobin maintenance to prevent or delay left ventricular mass growth in patients with CKD.", "Effects of early and late intervention with epoetin alpha on left ventricular mass among patients with chronic kidney disease (stage 3 or 4): results of a randomized clinical trial.", "Blood pressure in hemodialysis patients during amelioration of anemia with erythropoietin.", "A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients.", "Normalization of hematocrit in hemodialysis patients with cardiac disease does not increase blood pressure.", "The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin.", "The use of recombinant human erythropoietin in the correction of anemia in predialysis patients and its effect on renal function: a double-blind, placebo-controlled trial." ]

[ "Therapy with human recombinant erythropoietin (EPO) has been accepted as effective for renal anemia in dialysis patients. However, studies in rats have shown that correcting anemia with EPO may affect the progression of renal dysfunction. In humans, however, the effect of EPO on residual renal function is a matter of controversy. We, therefore, investigated whether the long-term administration of EPO to predialysis patients influences residual renal function. Anemic patients at the predialysis stage with a serum creatinine (Cr) concentration ranging from 2 to 4 (average 2.9) mg/dl and a hematocrit (Ht) of less than 30% were randomly assigned to two groups which consisted of anemic patients not treated with EPO (group I, untreated anemic controls, n = 31) and anemic patients treated with EPO (group II, treated anemics, n = 42). Patients with nonsevere or moderate anemia (Ht > 30%) with a Cr ranging from 2 to 4 (average 2.6) mg/dl were also recruited as nonanemic controls (group III, untreated nonanemic controls, n = 35). Blood pressure was controlled to the same degree among the three groups by combined treatment with calcium antagonists and angiotensin-converting enzyme inhibitors. All patients were kept strictly on a low-protein (0.6 g/kg/day) and a low-salt (7 g/day) diet. The degree of control of dietary protein and blood pressure and the frequency of angiotensin-converting enzyme inhibitor administration were comparable among the three groups. The primary end point for each patient was a doubling of the baseline Cr which yielded cumulative renal survival rates which were plotted against time. Ht rose significantly from 27.0+/-2.3 to 32.1+/-3.2% in group II (n = 42, p < 0.001) with a rate of increase of 0.4+/-0.06%/week. However, it declined from 27.9+/-1.8 to 25.3+/-1.9% in group I (n = 31, p < 0.001) and from 35.9+/-3.5 to 32.2+/-3.9% in group III (n = 35, p < 0.001). Cr doubled in 26 patients (84%) in group I as compared with 22 (52%) in group II and 21 (60%) in group III. The cumulative renal survival rates in groups II and III were significantly better than that in group I: p = 0.0003 (group I vs. group II) and p = 0.0024 (group I vs. group III). However, there was no difference in the renal survival rate between groups II and III (p = 0.3111). The better survival rate obtained in group II was attributable to the better survival rate for the nondiabetic patients in this group. The present study suggests that anemia, per se, is a factor in the progression of end-stage renal failure and that reversal of anemia by EPO can retard the progression of renal failure, especially in nondiabetic patients, provided that blood pressure control, rate of increase in Ht, and dietary protein restriction are appropriate.", "Hemoglobin levels below 10 g/dL lead to left ventricular (LV) hypertrophy, LV dilation, a lower quality of life, higher cardiac morbidity, and a higher mortality rate in end-stage renal disease. The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown.\n One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were randomly assigned to receive doses of epoetin alpha designed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks. The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation.\n In patients with concentric LV hypertrophy, the changes in LV mass index were similar in the normal and low target hemoglobin groups. The changes in cavity volume index were similar in both targets in the LV dilation group. Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved (8 mL/m2 per 1 g/dL hemoglobin decrement, P = 0.009). Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation. Normalization of hemoglobin led to improvements in fatigue (P = 0.009), depression (P = 0.02), and relationships (P = 0.004).\n Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation. It may, however, prevent the development of LV dilation, and it leads to improved quality of life.", "To determine the efficacy and safety of recombinant human erythropoietin (r-HuEPO) in predialysis renal patients.\n Randomized, double-blind, placebo-controlled trial for 8 weeks.\n Inpatient and outpatient facility in the Clinical Research Center of a university-based hospital.\n Fourteen adult subjects with renal insufficiency (mean serum creatinine, 473 mumol/L +/- 61 [6.2 +/- 0.8 mg/dL]) and anemia (mean hematocrit, 0.27 +/- 0.01).\n Recombinant human erythropoietin, 50, 100, or 150 IU/kg body weight or placebo given intravenously three times per week.\n Subjects who received active r-HuEPO showed a dose-dependent rise in hematocrit; mean hematocrit increased 41% from 0.27 +/- 0.01 to 0.38 +/- 0.01. At the same time, erythrocyte mass rose 43% from 13.7 +/- 0.6 mL/kg in the baseline state to 19.6 +/- 1.0 mL/kg after treatment. Maximal oxygen consumption during exercise increased 9% from 16.0 mL/min.kg +/- 1.8 to 17.5 mL/min.kg +/- 1.9.\n Recombinant human erythropoietin is effective and safe in ameliorating the anemia of pre-dialysis patients.", "nan", "In a two-way study, we treated renal anemia in chronic hemodialysis patients with recombinant human erythropoietin (rh-EPO) and followed heart morphology and function dynamics by echocardiography. Thirty-eight patients were randomly divided in two equal groups: the therapy group, treated with rh-EPO for 24 months, and the control group, not treated during the first 12 months and treated with rh-EPO during the second 12 months. Anemia was corrected, and hematocrit was maintained between 30 and 35 vol% by subcutaneous rh-EPO administration. Echocardiographic assessment was performed at the end of the untreated control phase and was repeated after 12 months of rh-EPO treatment in the control group and after 12 and 24 months of treatment in the therapy group. The results revealed significant morphologic, hemodynamic, and eventually functional changes. After 12 months of rh-EPO treatment, the end-diastolic volume (EDV) decreased from 135.8 +/- 23.7 to 109.8 +/- 25.3 ml, p < 0.001; stroke volume (SV) from 91.9 +/- 17.6 to 71.3 +/- 12.4 ml, p < 0.001; left ventricular mass-Devereux (LVMD) from 297.2 +/- 57.8 to 218.0 +/- 50.4 g, p < 0.01; cardiac output (CO) from 7,279 +/- 1,932 to 5,711 +/- 1,276 ml/min, p < 0.002; total peripheral resistance (TPR) rose from 1,330 +/- 390 to 1,707 +/- 373 dynes x s/cm5, p < 0.007. After 24 months, LVMD decreased further from 224.6 +/- 43.1 to 195.7 +/- 46.3 g, p < 0.004. The relaxation time index (RTI) decreased from 64.7 +/- 20.4 to 52.4 +/- 18.0 ms, p < 0.045, suggesting improved diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)", "Hypertension is a recognized complication of partial correction of anemia with recombinant human erythropoietin (epoetin) in hemodialysis patients. We used interdialytic ambulatory blood pressure (ABP) monitoring to study the effects of partially corrected anemia versus normal hematocrit (hct) on BP in hemodialysis patients.\n Repeated interdialytic ABP monitoring was performed for up to one year in 28 chronic hemodialysis patients with cardiac disease who were randomized to achieve and maintain normal hct levels (42 +/- 3%, group A) or anemic hct levels (30 +/- 3%, group B) with epoetin. Routine BP measurements obtained at dialysis treatments were also evaluated.\n Mean hct levels were 30.7 +/- 0.7% in group A and 30.6 +/- 0.7% in group B at baseline, then 39.3 +/- 1.2% (group A) and 33.5 +/- 0.6% (group B) at four months, and 42.0 +/- 1.1% (group A) and 30.4 +/- 1.0% (group B) at 12 months. Baseline ABP and routine dialysis unit BP levels were not different between the groups. At 2, 4, 8, and 12 months of follow-up, there were no statistically significant differences in any BP parameters between groups or increases in any BP parameters in either group A or group B patients compared with baseline. At 12 months, the mean nighttime diastolic BP (DBP) in group A patients was slightly but significantly lower than the mean daytime DBP (daytime DBP 76.6 +/- 1.9 mm Hg vs. nighttime DBP 72.9 +/- 2.1 mm Hg, P < 0.05). The mean daytime and nighttime BPs were not different from each other at two, four, and eight months in group A or at any time in group B, and in both groups, most patients had little diurnal change in BP.\n Correction of hct to normal with epoetin in chronic hemodialysis patients with cardiac disease did not cause increased BP as assessed by interdialytic ABP monitoring or by the measurement of routine predialysis and postdialysis BP. There was little diurnal change in systolic or diastolic BP at baseline or after correction of anemia to normal levels, and although mean nighttime DBP was lower than mean daytime DBP at 12 months in group A, the maintenance of normal hct levels did not affect the abnormal diurnal BP pattern seen at moderately anemic hct levels in most patients.", "Erythropoietin is known to improve outcomes in patients with anemia from chronic renal disease. However, there is uncertainty about the optimal timing of initiation of erythropoietin treatment in predialysis patients with non-severe anemia.\n We conducted a randomized controlled trial of early versus deferred initiation of erythropoietin in nondiabetic predialysis patients with serum creatinine 2 to 6 mg/dL and hemoglobin 9 to 11.6 g/dL. The early treatment arm was immediately started on 50 U/kg/wk of erythropoietin alpha with appropriate titration aiming for hemoglobin of > or =13 g/dL. The deferred treatment arm would start erythropoietin only when hemoglobin decreased to <9 g/dL. The primary end point was a composite of doubling of creatinine, renal replacement, or death.\n Eighty-eight patients were randomized (early treatment N= 45, deferred treatment N= 43) and followed for a median of 22.5 months. During follow-up, 13 versus 23 patients reached the primary end point in the two arms, respectively (log-rank P= 0.0078). The relative hazard for reaching an end point was 0.42 (P= 0.012). Adjusting for baseline serum creatinine, the adjusted relative hazard was 0.37 (P= 0.004), while the risk increased 2.23-fold (P < 0.001) per 1 mg/dL higher creatinine at baseline. The benefit was similar regardless of the baseline hemoglobin and proteinuria. No patients had any severe adverse events.\n Early initiation of erythropoietin in predialysis patients with non-severe anemia significantly slows the progression of renal disease and delays the initiation of renal replacement therapy.", "Anemia is already present in patients with moderate renal failure and is a major cause of the decline in exercise capacity seen in these patients. We examined the effects of erythropoietin (EPO) treatment in 12 predialytic uremic patients (EPO group: mean age 46 +/- 12 years; 6 men, 6 women) with a mean glomerular filtration rate (GFR) of 10 +/- 4 ml/min x 1.73 m2. These patients were compared to a control group of 8 patients (5 men, 3 women). The observation period was 3 months. The EPO group received 300 U/kg body weight i.v. once a week. The EPO group increased their total hemoglobin (THb) from 323 +/- 89 to 466 +/- 128 g (p less than 0.001) and their hemoglobin concentration from 86 +/- 8 to 117 +/- 11 milligrams (p less than 0.001). Their exercise capacity, measured by a standardized exercise test on a bicycle ergometer, increased from 128 +/- 45 to 147 +/- 57 W (p less than 0.01). The control group did not change their THb (349 +/- 124 and 357 +/- 131 g), hemoglobin (93 +/- 8 and 94 +/- 10 milligrams) or exercise capacity (98 +/- 49 and 101 +/- 50 W) during the observation period. There was a significant correlation between the increase in THb and the increase in exercise capacity in the EPO group (r = 0.81, p less than 0.005). The GFR was unchanged in both groups (EPO group: 10 +/- 4 and 10 +/- 6 ml/min x 1.73 m2; control group: 8 +/- 3 and 8 +/- 3 ml/min x 1.73 m2).(ABSTRACT TRUNCATED AT 250 WORDS)", "It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation. In this randomized, double-blind study, lower (9.5 to 11.5 g/dl) and higher (13.5 to 14.5 g/dl) hemoglobin targets were generated with epoetin alpha over 24 wk and maintained for an additional 72 wk. Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation. The primary outcome measure was left ventricular volume index (LVVI). The study enrolled 596 patients. Mean age, duration of dialysis therapy, baseline predialysis hemoglobin, and LVVI were 50.8 yr, 0.8 yr, 11.0 g/dl, and 69 ml/m2, respectively; 18% had diabetic nephropathy. Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl, respectively, at 24 wk. Percentage changes in LVVI between baseline and last value were similar (7.6% in the higher and 8.3% in the lower target group) as were the changes in left ventricular mass index (16.8 versus 14.2%). For the secondary outcomes, the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group (1.21 versus -2.31; P = 0.036). Overall adverse event rates were similar in both target groups; higher (P < 0.05) rates of skeletal pain, surgery, and dizziness were seen in the lower target group, and headache and cerebrovascular events were seen in the higher target group. Normalization of hemoglobin in incident hemodialysis patients does not have a beneficial effect on cardiac structure, compared with partial correction.", "The investigators evaluated the impact of recombinant human erythropoietin (r-HuEPO) therapy on health-related quality of life (HRQL) in predialysis chronic renal disease patients with anemia. Eighty-three patients were entered into a randomized, parallel-group, open-label clinical trial with follow-up evaluations over 48 weeks. Forty-three patients were assigned to r-HuEPO treatment, and 40 patients were assigned to an untreated control group. Hematocrit levels were measured at baseline and monthly. HRQL was assessed at baseline and at weeks 16, 32, and 48. The HRQL assessment included measures of physical function, energy, role function, health distress, cognitive function, social function, home management, sexual dysfunction, depression, and life satisfaction. Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group (P < 0.0001), and no changes were seen in the untreated group. Correction of anemia (hematocrit > or = 36) occurred in 79% of r-HuEPO-treated patients and 0% of control patients. Significant improvements in assessments of energy (P < 0.05), physical function (P < 0.05), home management (P < 0.05), social activity (P < 0.05), and cognitive function (P < 0.05) were found for the r-HuEPO-treated group. No changes were observed in the control group, except for a decrease in physical function (P < 0.05). Between-group differences favoring the r-HuEPO-treated group were found for energy (P < 0.05) and physical functioning (P < 0.05). In patients receiving r-HuEPO, significant improvements were seen in hemotocrit levels, and these increases resulted in improvements in HRQL.", "nan", "Recombinant human erythropoietin (r-HuEpo) is now available to correct the anaemia of end stage renal failure. The clinical consequences of increasing the haemoglobin concentration in children on dialysis are incompletely documented; a placebo controlled study is essential when assessing subjective changes, for example in appetite or other aspects of quality of life. A single blind, placebo controlled crossover study in 11 children with end stage renal failure was performed to assess the clinical benefits resulting from correction of anaemia. Ten of the 11 children completed 36 weeks of the study and seven completed both 24 week limbs. Subcutaneous administration of r-HuEpo twice a week resulted in an increase in haemoglobin concentration, from 73 to 112 g/l. This was associated with an objective improvement in exercise tolerance, and a subjective improvement in physical performance and health, and better school attendance. No consistent effect was seen on appetite, growth, psychosocial functioning, biochemical control, or peritoneal dialysis efficiency. A small but clinically unimportant increase in systolic and diastolic blood pressure was seen in five children. One child on antihypertensive treatment required an increase in dosage during r-HuEpo while another child required a reduction in treatment. These findings, together with the important cardiac benefits previously described during r-HuEpo treatment, support the use of r-HuEpo in all children with end stage renal failure and anaemia.", "The purpose of this study was to determine the efficacy of recombinant human erythropoietin (rHuEPO) given subcutaneously three times/week in patients with chronic renal failure and anemia (predialysis).\n Eleven patients with predialysis chronic renal failure participated in a double-blind, placebo-controlled study of subcutaneously administered erythropoietin. For 12 weeks, patients received either rHuEPO 100 mu/kg body weight three times/week subcutananeously or a placebo. After 12 weeks of placebo, patients now also received rHuEPO in a dose up to 150 mu/kg three times/week until target hematocrit was achieved. Throughout the study, blood pressure was monitored closely and blood work was obtained regularly for hemoglobin, hematocrit, reticulocyte count, and iron profile determinations.\n At 12 weeks, the hematocrit of the treated group had risen from 29% +/- 2% to 35% +/- 2% (p less than 0.001). The placebo group baseline hematocrit was 28% +/- 2% and at 12 weeks 26% +/- 2% After 12 weeks of rHuEPO therapy, the hematocrit of the prior placebo group was 32% +/- 2% (p less than 0.001 versus baseline). No significant change in biochemical parameters was noted. Mean blood pressure values were comparable before and after treatment. All protein ultimately required iron supplementation. In two patients, the rate of progression of renal failure appeared to increase as their hematocrit rose and rHuEPO was discontinued.\n It is concluded that rHuEPO given subcutaneously is an effective and safe therapy for patients with chronic renal failure who are anemic and who are not receiving dialysis.", "A prospective randomized study of the use of recombinant human erythropoietin (rHuEPO) in children with chronic renal disease was conducted to assess dosing requirements and side effects. Forty-four children with chronic renal failure, aged 4 months to 21 years, were studied. Twenty-five patients were pre dialysis, 10 on peritoneal dialysis, and 9 on hemodialysis. Patients received either 150 U/kg per week or 450 U/kg per week divided thrice weekly of rHuEPO for 12 weeks or until target hemoglobin (Hb) was attained. Dose was then adjusted to maintain a normal Hb. Eighty-two percent of patients reached target Hb by 7.9+/-5.6 weeks (mean+/-SD); 95% of patients in the high-dose group and 66% in the low-dose group reached target Hb within 12 weeks. The overall median rHuEPO dose at target Hb was 150 U/kg per week. Hemodialysis patients tended to require more rHuEPO to maintain a normal Hb (median 250 U/kg per week). Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks. Iron deficiency and/or hypertension occurred in 30% of children. In conclusion, rHuEPO at 150 U/kg per week is safe and effective in treating anemia in children with chronic renal disease.", "This randomized clinical trial is designed to assess whether the prevention and/or correction of anemia, by immediate versus delayed treatment with erythropoietin alfa in patients with chronic kidney disease, would delay left ventricular (LV) growth. Study design and sample size calculations were based on previously published Canadian data.\n One hundred seventy-two patients were randomly assigned. The treatment group received therapy with erythropoietin alfa subcutaneously to maintain or achieve hemoglobin (Hgb) level targets of 12.0 to 14.0 g/dL (120 to 140 g/L). The control/delayed treatment group had Hgb levels of 9.0 +/- 0.5 g/dL (90 +/- 5 g/L) before therapy was started: target level was 9.0 to 10.5 g/dL (90 to 105 g/L). Optimal blood pressure and parathyroid hormone, calcium, and phosphate level targets were prescribed; all patients were iron replete. The primary end point is LV growth at 24 months.\n One hundred fifty-two patients were eligible for the intention-to-treat analysis: mean age was 57 years, 30% were women, 38% had diabetes, and median glomerular filtration rate was 29 mL/min (0.48 mL/s; range, 12 to 55 mL/min [0.20 to 0.92 mL/s]). Blood pressure and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were similar in the control/delayed treatment and treatment groups at baseline. Erythropoietin therapy was administered to 77 of 78 patients in the treatment group, with a median final dose of 2,000 IU/wk. Sixteen patients in the control/delayed treatment group were administered erythropoietin at a median final dose of 3,000 IU/wk. There was no statistically significant difference between groups for the primary outcome of mean change in LV mass index (LVMI) from baseline to 24 months, which was 5.21 +/- 30.3 g/m2 in the control/delayed treatment group versus 0.37 +/- 25.0 g/m2 in the treatment group. Absolute mean difference between groups was 4.85 g/m2 (95% confidence interval, -4.0 to 13.7; P = 0.28). Mean Hgb level was greater in the treatment group throughout the study and at study end was 12.75 g/dL (127.5 g/L in treatment group versus 11.46 g/dL [114.6 g/L] in control/delayed treatment group; P = 0.0001). LV growth occurred in 20.1% in the treatment group versus 31% in the control/delayed treatment group (P = 0.136). In patients with a stable Hgb level, mean LVMI did not change (-0.25 +/- 26.7 g/m2), but it increased in those with decreasing Hgb levels (19.3 +/- 28.2 g/m2; P = 0.002).\n This trial describes disparity between observational and randomized controlled trial data: observed and randomly assigned Hgb level and LVMI are not linked; thus, there is strong evidence that the association between Hgb level and LVMI likely is not causal. Large randomized controlled trials with unselected patients, using morbidity and mortality as outcomes, are needed.", "It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular (LV) hypertrophy. A randomized controlled trial was performed with 155 patients with chronic kidney disease (creatinine clearance, 15 to 50 ml/min), with entry hemoglobin concentrations ([Hb]) of 110 to 120 g/L (female patients) or 110 to 130 g/L (male patients). Patients were monitored for 2 yr or until they required dialysis; the patients were randomized to receive epoetin alpha as necessary to maintain [Hb] between 120 and 130 g/L (group A) or between 90 and 100 g/L (group B). [Hb] increased for group A (from 112 +/- 9 to 121 +/- 14 g/L, mean +/- SD) and decreased for group B (from 112 +/- 8 to 108 +/- 13 g/L) (P < 0.001, group A versus group B). On an intent-to-treat analysis, the changes in LV mass index for the groups during the 2-yr period were not significantly different (2.5 +/- 20 g/m(2) for group A versus 4.5 +/- 20 g/m(2) for group B, P = NS). There was no significant difference between the groups in 2-yr mean unadjusted systolic BP (141 +/- 14 versus 138 +/- 13 mmHg) or diastolic BP (80 +/- 6 versus 79 +/- 7 mmHg). The decline in renal function in 2 yr, as assessed with nuclear estimations of GFR, also did not differ significantly between the groups (8 +/- 9 versus 6 +/- 8 ml/min per 1.73 m(2)). In conclusion, maintenance of [Hb] above 120 g/L, compared with 90 to 100 g/L, had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy. The maintenance of [Hb] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function.", "This study analyzed blood pressure in hemodialysis patients treated with epoetin beta in multicenter trials. Antihypertensive drugs were prescribed as usual. Placebo-controlled trials compared epoetin (100 to 150 U/kg; N = 151) with placebo (N = 78) for 82 days. Hemoglobin (108 +/- 18 versus 75 +/- 14 g/L) (mean +/- SD) and diastolic blood pressure (84 +/- 14 versus 78 +/- 15 mm Hg) were greater (P less than 0.05) after epoetin. Clinically important increases in blood pressure (increases in diastolic blood pressure greater than or equal to 10 mm Hg and/or drug therapy) were more frequent with epoetin (58 versus 37%; P = 0.005). A dose-response trial compared epoetin, 25 U/kg (N = 42), 100 U/kg (N = 40), and 200 U/kg (N = 39) for 138 days. Increases in hemoglobin were dose dependent, but clinically important increases in blood pressure were not. In analyses of all patients treated with epoetin (N = 272), no baseline or final level of hemoglobin, or rate of hemoglobin rise, was a threshold for a rise in blood pressure. Patients requiring antihypertensive drugs or having uncontrolled hypertension (diastolic blood pressure greater than 90 mm Hg) at baseline had decreases in blood pressure (P less than 0.05) with antihypertensive therapy. Thus, compared with placebo, 21% of patients had clinically important increases in blood pressure during amelioration of anemia. The baseline or final levels of hemoglobin, the extent or rate of hemoglobin rise, or uncontrolled hypertension or antihypertensive drug use at baseline were not confirmed as risks. Antihypertensive drug therapy was important for blood pressure control.", "Partial correction of renal anaemia with erythropoietin improves quality of life (QoL). We aimed to examine if normalization of haemoglobin with epoetin alfa in pre-dialysis and dialysis patients further improves QoL and is safe.\n 416 Scandinavian patients with renal anaemia [pre-dialysis, haemodialysis (HD) and peritoneal dialysis patients] were randomized to reach a normal haemoglobin of 135-160 g/l (n=216) or a subnormal haemoglobin of 90-120 g/l (n=200) with or without epoetin alfa. Study duration was 48-76 weeks. QoL was measured using Kidney Disease Questionnaires in 253 Swedish dialysis patients. Safety was examined in all patients.\n QoL improved, measured as a decrease in physical symptoms (P=0.02), fatigue (P=0.05), depression (P=0.01) and frustration (P=0.05) in the Swedish dialysis patients when haemoglobin was normalized. In pre-dialysis patients, diastolic blood pressure was higher in the normal compared with the subnormal haemoglobin group after 48 weeks. However, the progression rate of chronic renal failure was comparable. In the normal haemoglobin group (N-Hb), 51% had at least one serious adverse event compared with 49% in the subnormal haemoglobin group (S-Hb) (P=0.32). The incidence of thrombovascular events and vascular access thrombosis in HD patients did not differ. The mortality rate was 13.4% in the N-Hb group and 13.5% in the S-Hb group (P=0.98). Mortality decreased with increasing mean haemoglobin in both groups.\n Normalization of haemoglobin improved QoL in the subgroup of dialysis patients, appears to be safe and can be considered in many patients with end-stage renal disease.", "Since the earliest reports of the use of Epoetin alfa in hemodialysis patients, it has been described that Epoetin alfa may exacerbate preexisting hypertension or induce hypertension in End Stage Renal Disease (ESRD) patients not previously hypertensive. We undertook this study to determine if the correction of anemia in ESRD patients with cardiac disease from a hematocrit of 30+/-3% to 42+/-3% with the use of Epoetin alfa would result in increased blood pressure. This study was a substudy of the \"Normal hematocrit Study\".\n Thirty-one patients were randomized into one of two arms. Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoetin alfa to 42+/-3% and patients in Group B were maintained with a hematocrit of 30+/-3% throughout the course of the study. All patients had their blood pressure recorded with a 24 hour ambulatory BP device at study entry and at 28 weeks following randomization when they had achieved their target hematocrit. Pre-dialysis systolic and diastolic BP was also recorded.\n The mean hematocrit increased in Group A from 29.1+/-2.4% to 40.8+/-5.2% after 30 weeks. The hematocrit in Group B remained stable at 30+/-3% throughout the course of the study. There was no difference in mean daytime, mean nighttime or 24 hour systolic or diastolic blood pressure between Groups A and B at either baseline or follow-up. Neither was there a difference in mean pre-dialysis systolic or diastolic BP between Groups A or B at baseline or Follow-up. Four patients in Group A and 4 patients in Group B required an increase in their antihypertensive medication during the course of the study.\n It is possible to increase hematocrit to normal levels in hemodialysis with the administration of Epoetin alfa. The increase in hematocrit from 30+/-3% to 42+/-3% is not associated with increased blood pressure.", "In patients with end-stage renal disease, anemia develops as a result of erythropoietin deficiency, and recombinant human erythropoietin (epoetin) is prescribed to correct the anemia partially. We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis.\n We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis: 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent, and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study. The median duration of treatment was 14 months. The primary end point was the length of time to death or a first nonfatal myocardial infarction.\n After 29 months, there were 183 deaths and 19 first nonfatal myocardial infarctions among the patients in the normal-hematocrit group and 150 deaths and 14 nonfatal myocardial infarctions among those in the low-hematocrit group (risk ratio for the normal-hematocrit group as compared with the low-hematocrit group, 1.3; 95 percent confidence interval, 0.9 to 1.9). Although the difference in event-free survival between the two groups did not reach the prespecified statistical stopping boundary, the study was halted. The causes of death in the two groups were similar. The mortality rates decreased with increasing hematocrit values in both groups. The patients in the normal-hematocrit group had a decline in the adequacy of dialysis and received intravenous iron dextran more often than those in the low-hematocrit group.\n In patients with clinically evident congestive heart failure or ischemic heart disease who are receiving hemodialysis, administration of epoetin to raise their hematocrit to 42 percent is not recommended.", "Fourteen nondialyzed patients with chronic renal insufficiency (serum creatinine 265 to 972 mumol/L [3.0 to 11.0 mg/dL]) and severe anemia (hematocrit less than 30%) were randomized to receive either recombinant human erythropoietin (r-HuEPO) or a placebo subcutaneously thrice weekly for 12 weeks or until reaching a hematocrit of 38% to 40%. Anemia was significantly ameliorated in the treated patients. No acceleration in the progression of renal failure (1/serum creatinine v time) or change in serum potassium was noted for either the placebo or treated group over the 12-week period. Six of seven treated patients had a significant decrease in serum ferritin and percent transferrin saturation (plasma iron/total iron-binding capacity). This resulted in functional iron deficiency and the requirement for iron supplementation. The average systolic and diastolic blood pressure did not differ significantly between the two groups of patients during the study. Quality of life was improved in all r-HuEPO-treated patients but not in those in the placebo group. This study demonstrates the safety and efficacy of r-HuEPO in the correction of anemia in predialysis patients without adverse effects on renal function over a 12-week period. Improved patient well-being as a result of the correction of anemia resulted in one patient refusing appropriate initiation of dialysis therapy." ]

[ "2594037", "9808550", "2934438", "11208829", "6175137", "11369904", "18945306", "3579357", "15115499", "20889234", "11346336", "15204164" ]

[ "A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides.", "Prospective randomized multicenter clinical trial on the use of interferon -2a plus acitretin versus interferon -2a plus PUVA in patients with cutaneous T-cell lymphoma stages I and II.", "Intralesional interferon in the treatment of early mycosis fungoides.", "Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma.", "Transfer factor therapy in mycosis fungoides: a double-blind study.", "A phase III, randomized, double-blind, placebo-controlled study of peldesine (BCX-34) cream as topical therapy for cutaneous T-cell lymphoma.", "Psoralen plus ultraviolet A +/- interferon-alpha treatment resistance in mycosis fungoides: the role of tumour microenvironment, nuclear transcription factor-kappaB and T-cell receptor pathways.", "Recombinant interferon alfa-2b in plaque-phase mycosis fungoides. Intralesional and low-dose intramuscular therapy.", "A randomized cross-over study to compare PUVA and extracorporeal photopheresis in the treatment of plaque stage (T2) mycosis fungoides.", "A phase II placebo-controlled study of photodynamic therapy with topical hypericin and visible light irradiation in the treatment of cutaneous T-cell lymphoma and psoriasis.", "Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma.", "Imiquimod 5% cream in the treatment of mycosis fungoides--a pilot study." ]

[ "Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonradomized studies have suggested that early aggressive therapy may improve the prognosis in this usually fatal disease. We studied 103 patients with mycosis fungoides, who, after complete staging, were randomly assigned to receive either combination therapy, consisting of 3000 cGy of electron-beam radiation to the skin combined with parenteral chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine (n = 52) or sequential topical treatment (n = 51). The prognostic factors were well balanced in the two groups. Combined therapy produced considerable toxicity: 12 patients required hospitalization for fever and transient neutropenia, 5 had congestive heart failure, and 2 were later found to have acute nonlymphocytic leukemia. Patients receiving combined therapy had a significantly higher rate of complete response, documented by biopsy, than patients receiving conservative therapy (38 percent vs. 18 percent; P = 0.032). After a median follow-up of 75 months, however, there was no significant difference between the treatment groups in disease-free or overall survival. We conclude that early aggressive therapy with radiation and chemotherapy does not improve the prognosis for patients with mycosis fungoides as compared with conservative treatment beginning with sequential topical therapies.", "Cutaneous T-cell lymphoma (CTCL) constitutes a malignant proliferative disease involving mostly CD4(+) T cells arising in the skin. Because of the lack of curative treatment options, interferons (IFN) have been introduced into the therapy of CTCL. Although effective even in advanced disease, response rates were about 50% and the duration of response was short. To improve the results of interferon monotherapy, combinations of IFN with oral photochemotherapy (PUVA) or retinoids were investigated in nonrandomized trials showing higher response rates. We have therefore conducted this prospective randomized multicenter trial to compare these two combination therapies, ie, IFN plus PUVA and IFN plus acitretin. IFN -2a was administered at 9 MU three times weekly subcutaneously in both groups, with lower increasing doses during the first week. Photochemotherapy was applied after oral intake of 8-methoxypsoralen (0.6 mg/kg body weight) 5x weekly during the first 4 weeks, 3x weekly from weeks 5 through 23, and 2x weekly from weeks 24 through 48, with escalating doses beginning with 0.25 J/cm2. Twenty-five milligrams of acitretin was administered daily during the first week, and 50 mg was administered from weeks 2 through 48. Of 98 patients randomized in this study, 82 stage I and II patients were evaluable: 40 in the IFN+PUVA group and 42 in the IFN+acitretin group. With 70% complete remissions in the IFN+PUVA group, this treatment was significantly superior to the IFN+acitretin group with only 38.1% complete remissions. Time to response was significantly shorter in the IFN+PUVA group, with 18.6 weeks compared with 21.8 weeks in the IFN+acitretin group. Side effects were mostly mild to moderate and did not differ significantly in both treatment groups. However, there were more adverse events leading to study discontinuation in the IFN+acitretin group. Based on these findings, we conclude that IFN plus oral photochemotherapy is superior to IFN plus acitretin, inducing more complete remissions in patients with CTCL stages I and II.", "Twelve patients with early mycosis fungoides were enrolled in a randomized, double-blind, placebo-controlled study. Isolated plaques were injected three times a week with recombinant alpha 2-interferon in nine patients and with the vehicle in three patients. Two additional plaques were evaluated in each patient; one was left untreated, and another was treated topically with either placebo ointment or betamethasone ointment. Biopsies were taken from an untreated, representative plaque prior to treatment and from all test sites following treatment for light microscopy and T lymphocyte subsets. Three of the nine lesions injected with interferon cleared, and all showed improvement. Thirteen of eighteen noninjected lesions improved in patients who received interferon, showing a systemic effect. In the control group, none of the injected lesions improved and only two of the noninjected lesions showed any change. Histopathologic changes confirmed the clinical impression. This study shows that intralesional interferon may be given safely and has a beneficial effect, both locally and systemically.", "The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB389IL-2, Ontak [Ligand Pharmaceuticals Inc, San Diego, CA]) in patients with stage Ib to IVa cutaneous T-cell lymphoma (CTCL) who have previously received other therapeutic interventions.\n Patients with biopsy-proven CTCL that expressed CD25 on > or = 20% of lymphocytes were assigned to one of two dose levels (9 or 18 microg/kg/d) of denileukin diftitox administered 5 consecutive days every 3 weeks for up to 8 cycles. Patients were monitored for toxicity and clinical efficacy, the latter assessed by changes in disease burden and quality of life measurements. Antibody levels of antidenileukin diftitox and anti-interleukin-2 and serum concentrations of denileukin diftitox were also measured.\n Overall, 30% of the 71 patients with CTCL treated with denileukin diftitox had an objective response (20% partial response; 10% complete response). The response rate and duration of response based on the time of the first dose of study drug for all responders (median of 6.9 months with a range of 2.7 to more than 46.1 months) were not statistically different between the two doses. Adverse events consisted of flu-like symptoms (fever/chills, nausea/vomiting, and myalgias/arthralgias), acute infusion-related events (hypotension, dyspnea, chest pain, and back pain), and a vascular leak syndrome (hypotension, hypoalbuminemia, edema). In addition, 61% of the patients experienced transient elevations of hepatic transaminase levels with 17% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 microg/kg/d was similar, and there was no evidence of cumulative toxicity.\n Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions.", "Sixteen patients with mycosis fungoides (MF) were given either active transfer factor (TF) or heat-inactivated TF as additional therapy to topical nitrogen mustard or PUVA. The TF was prepared from non-selected healthy blood donors. The clinical evaluation after 2 years of therapy showed that among 8 patients treated with active TF, none went into complete remission of their disease 4 patients had partial remission, one was unchanged, 2 progressed, and one died of active MF. In the placebo-treated group, 5 patients achieved complete remission and 2 partial remission. One patient died early in the trial due to cardiac disease. Immunological studies during the first year of therapy revealed cutaneous anergy towards tuberculin in most patients. This anergy did not change during TF therapy and differed from normal lymphocyte reactivity in vitro after tuberculin stimulation. At the start of treatment the patients had diminished levels of T lymphocytes in peripheral blood. A temporary increase was observed in the total number of T lymphocytes in patients after one month of treatment with active TF. After one year the T lymphopenia had disappeared in both groups. The mitogen reactivity of lymphocytes was found to be normal (PHA, PWM) or somewhat reduced (Con A). It is concluded that under the conditions employed in this trial, TF was not able to prevent progression of early mycosis fungoides, when viewed over a period of 2 years.", "The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor.\n We attempted to determine the efficacy of peldesine (BCX-34) in a 1% dermal cream formulation as a treatment for cutaneous T-cell lymphoma (CTCL).\n Ninety patients with patch and plaque phase CTCL, histologically confirmed by a referee dermatopathologist, were enrolled in a randomized, double-blind, placebo-controlled study. BCX-34 dermal cream 1% or the vehicle cream (as a placebo control) was applied twice daily to the entire skin surface for up to 24 weeks. Efficacy of the topical therapy was assessed in terms of complete or partial (> or = 50%) clearing of patches and plaques.\n Of the 89 patients able to be examined, 43 received BCX-34 and 46 received the placebo vehicle cream. One patient withdrew early and was not analyzed. The two groups were well balanced for potential prognostic factors. A total of 28% (12/43) of the patients treated with BCX-34 showed a response, but 24% (11/46) of patients who received vehicle also responded (P =.677).\n Although BCX-34 dermal cream 1% was not significantly better than the control as therapy for patch and plaque-phase CTCL, this appears to be the first published placebo-controlled trial evaluating treatment for CTCL. Whether the vehicle cream has more than a placebo therapeutic effect is unclear. The relatively high (24%) placebo response rate should be kept in mind in assessing other treatments for early-stage CTCL.", "Interferon (IFN)-alpha is widely used in the treatment of mycosis fungoides (MF) and when used in combination with photochemotherapy (psoralen plus ultraviolet A, PUVA) both improved response and duration of complete remission have been reported. However, in spite of encouraging results of the initial studies, currently there is no information available on specific prognostic factors enabling prediction of patients' resistance to PUVA +/- IFN-alpha treatment.\n To identify factors responsible for resistance to PUVA +/- IFN-alpha treatment in MF patients.\n The gene expression profiling of pretreatment samples from 29 patients diagnosed as IA, IB or IIA stage of MF enrolled in a randomized PUVA vs. PUVA + IFN-alpha clinical trial was analysed using cDNA microarrays. A Cox model (SAM) and gene set enrichment analysis (GSEA) were used for identification of genes and biologically significant pathways related to resistance to treatment.\n Genes involved in NF-kappaB signalling, T-cell receptor (TCR) signalling, cytokine signalling and proliferation were differentially expressed between responders and nonresponders. Interestingly, expression of markers representative of those pathways was found not only in the tumoral cells, but also in specific subpopulations of macrophages, dendritic cells and other non-neoplastic cell types constituting the tumour microenvironment, likely involved in the promotion of survival and proliferation of cutaneous T-cell lymphoma.\n Gene expression changes in both the tumour and the tumour microenvironment are an important determinant of treatment outcome in early-stage MF patients. Some proinflammatory factors such as NF-kappaB, inflammatory cytokines and their receptors in addition to TCR-associated molecules could be promising targets for MF treatment.", "A two-part clinical trial was conducted to determine the therapeutic efficacy of recombinant interferon alfa-2b in plaque-phase mycosis fungoides. In an initial randomized double-blind study, each of six patients had two representative plaques injected intralesionally with 1 X 10(6) U of recombinant interferon alfa-2b per site and two control plaques injected with placebo three times weekly for four consecutive weeks. Complete clinical regression of disease was observed at ten of 12 recombinant interferon alfa-2b sites compared with one of 12 placebo-treated sites four weeks after treatment with injections was stopped. Subsequently, in an open-labeled study, five of these patients were treated intramuscularly with 5 X 10(6) U of recombinant interferon alfa-2b three times weekly for four weeks and two patients were treated with a second, more extended course of therapy lasting 12 to 16 weeks. Three of the five patients treated systemically showed some improvement overall, but the responses were judged not to be clinically significant. The differential response observed from intralesional and intramuscular injections may be related to differences in concentration of recombinant interferon alfa-2b achieved in lesional skin by the two methods of administration.", "PUVA is a well-established and effective treatment for plaque stage mycosis fungoides (MF) but its use is limited on a long-term basis because of the risk of cutaneous carcinogenesis. A further disadvantage is that nonexposed areas (sanctuary sites) often develop persistent disease. Therefore it is important to find alternative methods of treatment. Extracorporeal photopheresis (ECP) is a form of photochemotherapy that involves exposure of white blood cells to UVA with psoralens and can be effective in Sézary syndrome and erythrodermic cutaneous T-cell lymphoma. The aim of this study was to compare the efficacy of PUVA and ECP in the treatment of patients with T2 plaque stage (Stage 1B) MF who had a detectable peripheral blood T-cell clone. The study was of a cross-over design. Sixteen patients were randomized to receive either PUVA twice weekly for 3 months followed by ECP once monthly for 6 months at relapse, or vice-versa. Response was assessed by monthly skin scores and peripheral blood T-cell clonality. Ten patients received PUVA initially and six ECP initially. Eight patients completed the study. Skin scores taken at the completion of each treatment arm in patients who completed the study were 113 units better (confidence interval, 42-184 units) following 3 months PUVA than 6 months ECP (P = 0.002). Peripheral blood T-cell clones were detectable in all patients post-treatment. This study indicates that ECP is not effective in the treatment of plaque stage (1B/T2) MF even in patients with molecular evidence of a peripheral blood T-cell clone. Although PUVA was more effective than ECP, neither treatment modality cleared malignant T-cells from the peripheral blood.", "Hypericin is a known photodynamic agent that has been demonstrated to induce apoptosis in normal and malignant B and T lymphocytes, and has potential to treat benign and malignant disorders of the skin, including psoriasis and cutaneous T-cell lymphoma.\n We wished to test whether topical hypericin was an effective, safe, and well-tolerated therapy for patch or plaque phase mycosis fungoides and for plaque psoriasis.\n We conducted a phase II placebo-controlled clinical study in patients who had either patch or plaque phase mycosis fungoides or plaque type psoriasis vulgaris. Representative lesions were treated twice weekly for 6 weeks with topically applied hypericin or placebo followed 24 hours later by exposure to visible light at 8 to 20 J/cm(2).\n After 6 weeks of twice-weekly therapy, several concentrations of hypericin resulted in the significant improvement of treated skin lesions among the majority of patients with cutaneous T-cell lymphoma and psoriasis whereas the placebo vehicle was ineffective.\n The clinical trial involved a small number of patients.\n Overall, the data from this study support the conclusion that topical hypericin/visible light photodynamic therapy is an effective and well-tolerated alternative to standard psoralen plus ultraviolet A treatment of these disorders.\n Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.", "To determine the safety and efficacy of oral bexarotene (Targretin capsules; Ligand Pharmaceuticals Incorporated, San Diego, Calif).\n The effects of 2 randomized doses of 6.5 mg/m(2) per day (with crossover for progression) vs 650 mg/m(2) per day (later modified to 300 mg/m(2) per day) were evaluated in an open-label, multicenter, phase 2 and 3 study conducted between February 1997 and November 1998.\n Eighteen international cutaneous T-cell lymphoma clinics at academic referral centers.\n Fifty-eight patients with biopsy-proven stage IA through IIA cutaneous T-cell lymphoma that was refractory to (or patients were intolerant of) treatment or had reached at least a 6-month response plateau under at least 2 forms of prior therapy (median of 3.5 prior therapies).\n Bexarotene (Targretin capsules) administered once daily with meal for 16 weeks or longer.\n Primary end point classification of overall response rate of complete and partial remissions determined by either the Physician's Global Assessment of Clinical Condition or the objective Composite Assessment of Index Lesion Severity. Body surface area, time to response, duration of disease control, time to disease progression, individual index lesion signs and symptoms, and quality of life parameters were secondary outcomes.\n Responses (> or = 50% improvement) were seen in 3 (20%) of 15 patients with an initial dose at 6.5 mg/m(2) per day (95% confidence interval [CI], 0%-40%), 15 (54%) of 28 patients at 300 mg/m(2) per day (95% CI, 35%-72%), and 10 (67%) of 15 patients at above 300 mg/m(2) per day (95% CI, 43%-91%). The rate of progressive disease was 47%, 21%, and 13% at the same dose levels, respectively. Eight (73%) of 11 patients crossing over from 6.5 mg/m(2) per day to higher doses subsequently responded. The median duration of response from start of therapy could not be estimated for the 15 patients at 300 mg/m(2) per day owing to low relapse rates in 2 patients (13%); at higher doses it was 516 days. The following drug-related adverse effects were reversible and treatable: hypertriglyceridemia (46 patients [79%]), hypercholesterolemia (28 patients [48%]), headache (27 patients [47%]), central hypothyroidism (23 patients [40%]), asthenia (21 patients [36%]), and leukopenia (16 patients [28%]). No cases of drug-related neutropenic fever, sepsis, or death occurred. Pancreatitis occurred in 3 patients with triglyceride levels higher than 14.69 mmol/L (1300 mg/dL), all of whom were taking 300 mg/m(2) or more of oral bexarotene per day.\n Bexarotene (Targretin capsules) (the first retinoid X receptor-selective rexinoid) was well tolerated and effective as an oral treatment for 15 (54%) of 28 patients with refractory or persistent early-stage cutaneous T-cell lymphoma at doses of 300 mg/m(2) per day. Hypertriglyceridemia and hypothyroidism require monitoring but are reversible and manageable with concomitant medication.", "nan" ]

[ "3983336", "7897085", "6810839", "776313", "359081", "6143340" ]

[ "Implications of noncompliance on research in affective disorders.", "A 24-month follow-up study of unipolar subjects: a comparison between lithium and fluvoxamine.", "Lithium carbonate and imipramine in the prophylaxis of unipolar and bipolar II illness: a prospective, placebo-controlled comparison.", "A double-blind comparison of lithium carbonate and maprotiline in the prophylaxis of the affective disorders.", "Mianserin and lithium in the prophylaxis of depression.", "Continuation therapy with lithium and amitriptyline in unipolar depressive illness: a randomized, double-blind, controlled trial." ]

[ "nan", "The authors compared rates of new episodes in a sample of 64 unipolar subjects treated with fluvoxamine (n = 32) and lithium (n = 32) during a follow-up period of 24 months. Unipolar patients on lithium treatment had a worse outcome with a higher frequency of new recurrences compared with of new recurrences compared with patients on fluvoxamine during the course of preventive treatment.", "Twenty-seven patients with recurrent unipolar depression and 22 with bipolar II illness in remission for at least six months were randomly assigned on a double-blind basis to treatment regimens using lithium carbonate, imipramine hydrochloride, lithium carbonate plus imipramine, or placebo. Lithium carbonate was found to help prevent depressive relapse among patients with unipolar disease, and relapse of any type among those with bipolar II disease. No effect or interaction of imipramine was found in either group. These results add to a growing body of data that suggest the usefulness of lithium carbonate in the prophylaxis of unipolar depressive illness. The relative usefulness of lithium carbonate and imipramine requires further study.", "A double-blind prospective study was carried out comparing the prophylactic effect of maprotiline and lithium carbonate over a period of one year in patients suffering from recurrent affective disorders. The average Affective Morbidity Index was lower, but not significantly so, in patients treated with lithium. A further analysis, based on dividing patients into those with no affective morbidity and those who showed some affective morbidity during the study, demonstrated lithium carbonate to be significantly superior to maprotiline both in the group as a whole and in unipolar depressives. A correlation between high plasma maprotiline concentration and low morbidity was observed and was in line with an earlier report. A highly significant negative correlation (r=-0-97; p less than 0-001) was found between plasma maprotiline concentration and body weight. Although the results showed lithium carbonate to be superior to maprotiline in the study, it should be emphasized that the plasma levels of lithium were constantly monitored and maintained at what is considered to be its optimum concentration, whereas the maprotiline treated patients were kept on a fixed dosage regime irrespective of plasma levels.", "Forty-one out-patients with a history of at least three attacks of depressive illness were randomly allocated to treatment on a double-blind basis for one year with either mianserin 20 mg three times daily plus placebo lithium tablets, or to lithium tablets once daily plus placebo mianserin tablets. After one year, the dosage of mianserin was increased to 30 mg t.d.s. for a further six months. All but three of the patients had previously been stabilized on prophylactic lithium therapy. Lithium was found to be significantly superior to mianserin in avoiding admission to hospital or ECT. The overall affective morbidity index, calculated from global rating, showed no significant difference between drugs, but the index of the mianserin group was higher in the second six months than in the first. The lithium group showed no such change. Lithium remains the choice for the prophylaxis of unipolar recurrent depressive illness.", "A detailed analysis of the results of a multi-centre clinical trial shows that, while the relapse rate following recovery from an operationally defined depressive illness was smaller among patients subsequently treated with either amitryptiline or lithium than with a placebo, there was no clinically significant difference between the prophylactic efficacy of the 2 antidepressants. An account is given of the relative adverse effects of the treatments, and the implications of the findings are discussed." ]

[ "11099583" ]

[ "Baby CareLink: using the internet and telemedicine to improve care for high-risk infants." ]

[ "To evaluate an Internet-based telemedicine program designed to reduce the costs of care, to provide enhanced medical, informational, and emotional support to families of very low birth weight (VLBW) infants during and after their neonatal intensive care unit (NICU) stay.\n Baby CareLink is a multifaceted telemedicine program that incorporates videoconferencing and World Wide Web (WWW) technologies to enhance interactions between families, staff, and community providers. The videoconferencing module allows virtual visits and distance learning from a family's home during an infant's hospitalization as well as virtual house calls and remote monitoring after discharge. Baby CareLink's WWW site contains information on issues that confront these families. In addition, its security architecture allows efficient and confidential sharing of patient-based data and communications among authorized hospital and community users.\n A randomized trial of Baby CareLink was conducted in a cohort of VLBW infants born between November 1997 and April 1999. Eligible infants were randomized within 10 days of birth. Families of intervention group infants were given access to the Baby CareLink telemedicine application. A multimedia computer with WWW browser and videoconferencing equipment was installed in their home within 3 weeks of birth. The control group received care as usually practiced in this NICU. Quality of care was assessed using a standardized family satisfaction survey administered after discharge. In addition, the effect of Baby CareLink on hospital length of stay as well as family visitation and interactions with infant and staff were measured.\n Of the 176 VLBW infants admitted during the study period, 30 control and 26 study patients were enrolled. The groups were similar in patient and family characteristics as well as rates of inpatient morbidity. The CareLink group reported higher overall quality of care. Families in the CareLink group reported significantly fewer problems with the overall quality of care received by their family (mean problem score: 3% vs 13%). In addition, CareLink families also reported greater satisfaction with the unit's physical environment and visitation policies (mean problem score: 13% vs 50%). The frequency of family visits, telephone calls to the NICU, and holding of the infant did not differ between groups. The duration of hospitalization until ultimate discharge home was similar in the 2 groups (68.5 +/- 28.3 vs 70.6 +/- 35.6 days). Among infants born weighing <1000 g (n = 31) there was a tendency toward shorter lengths of stay (77.4 +/- 26.2 vs 93.1 +/- 35.6 days). All infants in the CareLink group were discharged directly to home whereas 6/30 (20%) of control infants were transferred to community hospitals before ultimate discharge home.\n CareLink significantly improves family satisfaction with inpatient VLBW care and definitively lowers costs associated with hospital to hospital transfer. Our data suggest the use of telemedicine and the Internet support the educational and emotional needs of families facilitating earlier discharge to home of VLBW infants. We believe that further extension of the Baby CareLink model to the postdischarge period will significantly improve the coordination and efficiency of care." ]

[ "10199766", "10683055", "10979879", "1548998", "11740194", "2375667" ]

[ "Effects of pharmacological doses of nandrolone decanoate and progressive resistance training in immunodeficient patients infected with human immunodeficiency virus.", "Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels.", "Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial.", "Effects of exercise training on men seropositive for the human immunodeficiency virus-1.", "Effects of whey protein and resistance exercise on body cell mass, muscle strength, and quality of life in women with HIV.", "Progressive resistance exercise: effect on muscle function and anthropometry of a select AIDS population." ]

[ "This nonplacebo-controlled, open label, randomized study was conducted to test the hypotheses that pharmacological doses of nandrolone decanoate would increase lean body tissue, muscle mass, and strength in immunodeficient human immunodeficiency virus-infected men, and that these effects would be enhanced with progressive resistance training (PRT). Thirty human immunodeficiency virus-positive men with fewer than 400 CD4 lymphocytes/mm3 were randomly assigned to receive weekly injections of nandrolone alone or in combination with supervised PRT at 80% of the one-repetition maximum three times weekly for 12 weeks. Total body weight increased significantly in both groups (3.2 +/- 2.7 and 4.0 +/- 2.0 kg, respectively; P < 0.001), with increases due primarily to augmentation of lean tissue. Lean body mass determined by dual energy x-ray absorptiometry increased significantly more in the PRT group (3.9 +/- 2.3 vs. 5.2 +/- 5.7 kg, respectively; P = 0.03). Body cell mass by bioelectrical impedance analysis increased significantly (P < 0.001) in both groups (2.6 +/- 1.0 vs. 2.9 +/- 0.8 kg), but to a similar magnitude (P = NS). Significant increases in cross-sectional area by magnetic resonance imaging of total thigh muscles (1538 +/- 767 and 1480 +/- 532 mm2), quadriceps (705 +/- 365 and 717 +/- 288 mm2), and hamstrings (842 +/- 409 and 771 +/- 295 mm2) occurred with both treatment strategies (P < 0.001 for the three muscle areas); these increases were similar in both groups (P = NS). By the one-repetition method, strength increased in both upper and lower body exercises, with gains ranging from 10.3-31% in the nandrolone group and from 14.4-53.0% in the PRT group (P < 0.006 with one exception). Gains in strength were of significantly greater magnitude in the PRT group (P < or = 0.005 for all comparisons), even after correction for lean body mass. Thus, pharmacological doses of nandrolone decanoate yielded significant gains in total weight, lean body mass, body cell mass, muscle size, and strength. The increases in lean body mass and muscular strength were significantly augmented with PRT.", "Previous studies of testosterone supplementation in HIV-infected men failed to demonstrate improvement in muscle strength. The effects of resistance exercise combined with testosterone supplementation in HIV-infected men are unknown.\n To determine the effects of testosterone replacement with and without resistance exercise on muscle strength and body composition in HIV-infected men with low testosterone levels and weight loss.\n Placebo-controlled, double-blind, randomized clinical trial conducted from September 1995 to July 1998 at a general clinical research center.\n Sixty-one HIV-infected men aged 18 to 50 years with serum testosterone levels of less than 12.1 nmol/L (349 ng/dL) and weight loss of 5% or more in the previous 6 months, 49 of whom completed the study.\n Participants were randomly assigned to 1 of 4 groups: placebo, no exercise (n = 14); testosterone enanthate (100 mg/wk intramuscularly), no exercise (n = 17); placebo and exercise (n = 15); or testosterone and exercise (n = 15). Treatment duration was 16 weeks.\n Changes in muscle strength, body weight, thigh muscle volume, and lean body mass compared among the 4 treatment groups.\n Body weight increased significantly by 2.6 kg (P<.001) in men receiving testosterone alone and by 2.2 kg (P = .02) in men who exercised alone but did not change in men receiving placebo alone (-0.5 kg; P = .55) or testosterone and exercise (0.7 kg; P = .08). Men treated with testosterone alone, exercise alone, or both experienced significant increases in maximum voluntary muscle strength in leg press (range, 22%-30%), leg curls (range, 18%-36%), bench press (range, 19%-33%), and latissimus pulls (range, 17%-33%). Gains in strength in all exercise categories were greater in men assigned to the testosterone-exercise group or to the exercise-alone group than in those assigned to the placebo-alone group. There was a greater increase in thigh muscle volume in men receiving testosterone alone (mean change, 40 cm3; P<.001 vs zero change) or exercise alone (62 cm3; P = .003) than in men receiving placebo alone (5 cm3; P = .70). Average lean body mass increased by 2.3 kg (P = .004) and 2.6 kg (P<.001), respectively, in men who received testosterone alone or testosterone and exercise but did not change in men receiving placebo alone (0.9 kg; P = .21). Hemoglobin levels increased in men receiving testosterone but not in those receiving placebo.\n Our data suggest that testosterone and resistance exercise promote gains in body weight, muscle mass, muscle strength, and lean body mass in HIV-infected men with weight loss and low testosterone levels. Testosterone and exercise together did not produce greater gains than either intervention alone.", "Substantial loss of muscle mass occurs among men with AIDS wasting.\n To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting.\n Randomized, controlled trial.\n University hospital.\n 54 eugonadal men with AIDS wasting (weight < 90% ideal body weight or weight loss > 10%).\n In a 2 x 2 factorial design, patients were assigned to receive testosterone enanthate (200 mg/wk) or placebo injections and progressive resistance training (three times weekly) or no training for 12 weeks.\n Cross-sectional muscle area and other indices of muscle mass.\n Cross-sectional muscle area increased in response to training compared with nontraining (change in arm muscle mass, 499 +/- 349 mm2 vs. 206 +/- 264 mm2 [P = 0.004]; change in leg muscle mass, 1106 +/- 854 mm2 vs. 523 +/- 872 mm2 [P = 0.045]) and in response to testosterone therapy compared with placebo (change in arm muscle mass, 512 +/- 371 mm2 vs. 194 +/- 215 mm2 [P< 0.001]; change in leg muscle mass, 1,236 +/- 881 mm2 vs. 399 +/- 729 mm2 [P = 0.002]). Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo (-0.03 +/- 0.13 mmol/L vs. 0.05 +/- 0.13 mmol/L [-1 +/- 5 mg/dL vs. 2 +/- 5 mg/dL]; P= 0.011) and increased in response to training compared with nontraining (0.05 +/- 0.13 mmol/L vs. 0.00 +/- 0.16 mmol/L [2 +/- 5 mg/dL vs. 0 +/- 6 mg/dL]; P = 0.052).\n In contrast to anabolic therapies that may have adverse effects on metabolic variables, supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting.", "We examined the effects of chronic exercise on fitness and immune status in Caucasian males (34.9 +/- 5.6 yr) diagnosed by Western blot as seropositive for the HIV-1 virus. The exercise regimen involved 12 wk of 1 h sessions 3 d.wk: 20 min of cycle exercise at 60-80% HRreserve was followed by 35 min of strength and flexibility training. After matching subjects on health status (modified Walter Reed criteria), subjects (N = 37) were randomly assigned to exercise or a counseling control condition. Changes in strength, responses to the YMCA cycle test, and serum lymphocytes were tested by MANOVA in a condition (exercise or counseling)-by-time (pretest, posttest) design with repeated measures on time. Results indicated significant (P less than 0.001) group-by-time interactions for strength (N.m) (chest press and leg extension) and for HR (beats.min-1) and total time (TT) on the cycle test at 150 W. Strength and TT increased and HR decreased in the exercise condition, while control subjects did not change. Total leukocyte, lymphocyte, CD4+, and CD8+ cell counts, and the CD4+/CD8+ ratio were statistically unchanged for each condition. We conclude that HIV-1+ men, including those symptomatic for AIDS-related complex, can experience significant increases in neuromuscular strength and cardiorespiratory fitness without changes in lymphocyte phenotypes or clinical diagnosis when the exercise regimen is prescribed and monitored in accordance with ACSM guidelines for healthy adults.", "To determine the effects of whey protein, resistance exercise, and combined protein and exercise treatment on body cell mass (BCM), muscle strength, and quality of life (QOL) in HIV-infected women with reduced BCM.\n Prospective, randomized, controlled trial at a university hospital in New York City.\n A volunteer sample of 30 HIV-infected women were randomized to whey protein (PRO), progressive resistance exercise (PRE), or combined treatment (PRO-PRE) for 14 weeks after a 6-week control period. The main outcome measures were body weight, BCM, skeletal muscle, fat mass, muscle strength, and QOL.\n There were no significant changes in BCM, strength, or QOL during the control period. PRO patients gained 3.6 kg (P = 0.001), and 2.5 kg fat (P = 0.002) with no change in BCM (0.5 kg; P = 0.07) or skeletal muscle (0.6 kg; P = 0.12). The PRE group increased BCM (0.74 kg;P = 0.03) and skeletal muscle (1.2 kg; P < 0.001) and decreased fat (1.7 kg; P = 0.02). PRO-PRE increased BCM (0.61 kg; P = 0.01) without change in skeletal muscle (0.6 kg; P = 0.30). Strength increased for both exercise groups (range, 40.6-95.3%; P < 0.001). The QOL physical activity score improved for PRE (P = 0.02) and worsened for PRO (P = 0.01).\n Resistance exercise significantly increased BCM, muscle mass, muscle strength, and QOL in HIV-infected women with reduced BCM. Whey protein had little effect on BCM accrual. Combined protein and exercise did not increase BCM in excess of gains achieved by exercise alone.", "Substantial body tissue wasting has been reported in acquired immune deficiency syndrome (AIDS) patients. The purpose of this investigation was to determine if progressive resistance exercise (PRE) would improve muscle function and increase body dimensions and mass in AIDS patients. The subjects were 24 male outpatient volunteers, status posttherapy for acute pneumocystis carinii pneumonia. Subjects were randomly assigned to control (n = 12) or experimental (n = 12) subsets. All subjects underwent muscle function testing on 12 variables of torque, force, power, and work; three variables of anthropometry were assessed. The experimental group engaged in PRE three times per week for six weeks. The control group did not exercise beyond their usual daily living activities. Both groups were retested at the end of six weeks. In comparison to the control group, the experimental group significantly increased in 13 of the 15 study variables. Thus, during the nonacute stage of AIDS, physiologic adaptation occurred that improved muscle function and increased body dimensions and mass." ]

[ "10528036", "18669816", "16162746", "17901413", "16306520", "15665326", "14711911", "19570573", "9655733", "20007927", "19996196", "1859050", "2669218" ]

[ "A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis.", "Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial.", "Anticoagulant therapy for idiopathic pulmonary fibrosis.", "BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis.", "High-dose acetylcysteine in idiopathic pulmonary fibrosis.", "Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis.", "A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis.", "Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial.", "Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosis. A randomized prospective study. Members of the Lung Study Group.", "Imatinib treatment for idiopathic pulmonary fibrosis: Randomized placebo-controlled trial results.", "Pirfenidone in idiopathic pulmonary fibrosis.", "Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial.", "Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis." ]

[ "Patients with idiopathic pulmonary fibrosis have progressive scarring of the lung and usually die within four to five years after symptoms develop. Treatment with oral glucocorticoids is often ineffective. We conducted an open, randomized trial of treatment with a combination of interferon gamma-1b, which has antifibrotic properties, and an oral glucocorticoid. We studied 18 patients with idiopathic pulmonary fibrosis who had not had responses to glucocorticoids or other immunosuppressive agents. Nine patients were treated for 12 months with oral prednisolone alone (7.5 mg daily, which could be increased to 25 to 50 mg daily), and nine with a combination of 200 microg of interferon gamma-1b (given three times per week subcutaneously) and 7.5 mg of prednisolone (given once a day).\n All the patients completed the study. Lung function deteriorated in all nine patients in the group given prednisolone alone: total lung capacity decreased from a mean (+/-SD) of 66+/-8 percent of the predicted value at base line to 62+/-6 percent at 12 months. In contrast, in the group receiving interferon gamma-1b plus prednisolone, total lung capacity increased (from 70+/-6 percent of the predicted value at base line to 79+/-12 percent at 12 months, P<0.001 for the difference between the groups). In the group that received interferon gamma-1b plus prednisolone, the partial pressure of arterial oxygen at rest increased from 65+/-9 mm Hg at base line to 76+/-8 mm Hg at 12 months, whereas in the group that received prednisolone alone it decreased from 65+/-6 to 62+/-4 mm Hg (P<0.001 for the difference in the change from baseline values between the two groups); on maximal exertion, the value increased from 55+/-6 to 65+/-8 mm Hg in the group that received combined treatment and decreased from 55+/-6 mm Hg to 52+/-5 mm Hg in the group given prednisolone alone (P<0.001). The side effects of interferon gamma-1b, such as fever, chills, and muscle pain, subsided within the first 9 to 12 weeks.\n In a preliminary study, 12 months of treatment with interferon gamma-1b plus prednisolone was associated with substantial improvements in the condition of patients with idiopathic pulmonary fibrosis who had had no response to glucocorticoids.", "An efficacious medical therapy for idiopathic pulmonary fibrosis (IPF) remains elusive.\n To explore the efficacy and safety of etanercept in the treatment of IPF.\n This was a randomized, prospective, double-blind, placebo-controlled, multicenter exploratory trial in subjects with clinically progressive IPF. Primary endpoints included changes in the percentage of predicted FVC and lung diffusing capacity for carbon monoxide corrected for hemoglobin (Dl(CO(Hb))) and change in the alveolar to arterial oxygen pressure difference P(a-a)(O(2)) at rest from baseline over 48 weeks.\n Eighty-eight subjects received subcutaneous etanercept (25 mg) or placebo twice weekly as their sole treatment for IPF. No differences in baseline demographics and disease status were detected between treatment groups; the mean time from first diagnosis was 13.6 months and mean FVC was 63.9% of predicted. At 48 weeks, no significant differences in efficacy endpoints were observed between the groups. A nonsignificant reduction in disease progression was seen in several physiologic, functional, and quality-of-life endpoints among subjects receiving etanercept. There was no difference in adverse events between treatment groups.\n In this exploratory study in patients with clinically progressive IPF, etanercept was well tolerated. Although there were no differences in the predefined endpoints, a decreased rate of disease progression was observed on several measures. Further evaluation of TNF antagonists in the treatment of IPF may be warranted. Clinical trial registered with www.clinicaltrials.gov (NCT 00063869).", "To evaluate the effect of anticoagulant therapy on the survival of patients with idiopathic pulmonary fibrosis (IPF).\n Prospective study.\n Five hospitals located in the Miyagi prefecture in Japan, including a university hospital, a Red Cross hospital, two public general hospitals, and a municipal hospital.\n Fifty-six patients with IPF (mean age, 69.4 years; range, 47 to 89) admitted to the hospitals from April 2001 to April 2004.\n Patients were assigned to receive prednisolone alone or prednisolone plus anticoagulant therapy. The anticoagulants included oral warfarin in an outpatient setting and low-molecular-weight heparin for rehospitalized patients with severely progressive respiratory failure.\n There was no difference in baseline characteristics, including age, gender, clinical condition, pulmonary function, and plasma d-dimer level between the non-anticoagulant group and the anticoagulant group. The overall survival and hospitalization-free periods were assessed. There was a significant difference between survival curves of the non-anticoagulant group and the anticoagulant group, with a 2.9 hazard ratio (p = 0.04, Cox regression model). There was no significant difference in the probability of a hospitalization-free period between groups. The major cause of clinical deterioration was acute exacerbation during follow-up in the present study. Therefore, the mortality and plasma d-dimer levels in patients with an acute exacerbation were also assessed. The mortality associated with acute exacerbations of IPF in the anticoagulant group was significantly reduced compared to that in the non-anticoagulant group (18% vs 71%, respectively; p = 0.008, Fisher Exact Test). Furthermore, the plasma d-dimer levels in patients who died were significantly higher than those in survivors during acute exacerbation of IPF (3.3 +/- 2.3 microg/mL vs 0.9 +/- 0.7 microg/mL, p < 0.0001). Histologic analysis performed in three patients who died due to an exacerbation of IPF in the non-anticoagulant group demonstrated the features of usual interstitial pneumonia and acute lung injury.\n Our data suggested that plasma d-dimer levels are associated with mortality in patients with an acute exacerbation of IPF, and that anticoagulant therapy has a beneficial effect on survival in patients with IPF.", "Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease lacking effective treatment.\n To determine the effects of bosentan on exercise capacity and time to disease progression in patients with IPF.\n In a double-blind, multicenter trial, patients with IPF were randomized to receive oral bosentan 62.5 mg twice daily for 4 weeks, increased to 125 mg twice daily thereafter, or placebo, for 12 months or longer. The primary efficacy endpoint was change from baseline up to Month 12 in exercise capacity, as measured by a modified six-minute-walk test. Secondary endpoints were time to death or disease progression (worsening pulmonary function tests [PFTs] or acute decompensation), change in PFT scores, and quality of life (QOL) assessed using Short-Form 36 and St. George's Respiratory Questionnaire.\n A total of 158 patients randomly received bosentan (n = 74) or placebo (n = 84). Bosentan showed no superiority over placebo in six-minute-walk distance (6MWD) up to Month 12, the primary efficacy endpoint. A trend in favor of bosentan was observed in the secondary endpoint of time to death or disease progression (hazard ratio [HR], 0.613; 95% confidence interval [CI], 0.328-1.144; P = 0.119), which was more pronounced in a patient subgroup diagnosed using surgical lung biopsy (post hoc analysis; HR, 0.315; 95% CI, 0.126-0.789; P = 0.009). Changes from baseline up to Month 12 in assessments of dyspnea and QOL favored treatment with bosentan. No unexpected adverse events were reported.\n Bosentan treatment in patients with IPF did not show superiority over placebo on 6MWD. A trend in delayed time to death or disease progression, and improvement in QOL, was observed with bosentan. The more pronounced treatment effect in patients with biopsy-proven IPF warrants further investigation. Clinical trial registered with www.clinicaltrials.gov (NCT 00071461).", "Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis.\n We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) added to standard therapy with prednisone plus azathioprine. The primary end points were changes between baseline and month 12 in vital capacity and in single-breath carbon monoxide diffusing capacity (DL(CO)).\n A total of 182 patients were randomly assigned to treatment (92 to acetylcysteine and 90 to placebo). Of these patients, 155 (80 assigned to acetylcysteine and 75 to placebo) had usual interstitial pneumonia, as confirmed by high-resolution computed tomography and histologic findings reviewed by expert committees, and did not withdraw consent before the start of treatment. Fifty-seven of the 80 patients taking acetylcysteine (71 percent) and 51 of the 75 patients taking placebo (68 percent) completed one year of treatment. Acetylcysteine slowed the deterioration of vital capacity and DL(CO): at 12 months, the absolute differences in the change from baseline between patients taking acetylcysteine and those taking placebo were 0.18 liter (95 percent confidence interval, 0.03 to 0.32), or a relative difference of 9 percent, for vital capacity (P=0.02), and 0.75 mmol per minute per kilopascal (95 percent confidence interval, 0.27 to 1.23), or 24 percent, for DL(CO) (P=0.003). Mortality during the study was 9 percent among patients taking acetylcysteine and 11 percent among those taking placebo (P=0.69). There were no significant differences in the type or severity of adverse events between patients taking acetylcysteine and those taking placebo, except for a significantly lower rate of myelotoxic effects in the group taking acetylcysteine (P=0.03).\n Therapy with acetylcysteine at a dose of 600 mg three times daily, added to prednisone and azathioprine, preserves vital capacity and DL(CO) in patients with idiopathic pulmonary fibrosis better than does standard therapy alone.\n Copyright 2005 Massachusetts Medical Society.", "Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without an effective therapy to date. In a double-blind, randomized, placebo-controlled trial, 107 patients were prospectively evaluated for efficacy of a novel compound, pirfenidone. The difference in the change in the lowest oxygen saturation by pulse oximetry (SpO2) during a 6-minute exercise test, the primary endpoint, from baseline to 6 months was not significant between the two groups (p = 0.0722). In a prespecified subset of patients who maintained a SpO2 greater than 80% during a 6-minute exercise test at baseline, the lowest SpO2 improved during a 6-minute exercise test in the pirfenidone group at 6 and 9 months (p = 0.0069 and 0.0305, respectively). Positive treatment effect was demonstrated in secondary endpoints: (1) change in VC measurements at 9 months (p = 0.0366) and (2) episodes of acute exacerbation of IPF occurring exclusively in the placebo group during the 9 months (p = 0.0031). Significant adverse events were associated with pirfenidone; however, adherence to treatment regimen was similar between pirfenidone and placebo groups. In conclusion, treatment with pirfenidone improved VC and prevented acute exacerbation of IPF during the 9 months of follow-up. Future long-term studies are needed to clarify the overall safety and efficacy of pirfenidone in IPF.", "Idiopathic pulmonary fibrosis is a progressive, fatal disease with no known efficacious therapy.\n In a double-blind, multinational trial, we randomly assigned 330 patients with idiopathic pulmonary fibrosis that was unresponsive to corticosteroid therapy to receive subcutaneous interferon gamma-1b or placebo.\n Over a median of 58 weeks, interferon gamma-1b therapy did not significantly affect the primary end point of progression-free survival, defined as the time to disease progression or death, and no significant treatment effect was observed on measures of lung function, gas exchange, or the quality of life. Ten percent of patients in the interferon gamma-1b group died, as compared with 17 percent of patients in the placebo group (P=0.08). Treatment with interferon gamma-1b was associated with more frequent constitutional symptoms. However, the rates of treatment adherence and premature discontinuation of treatment were similar in the two groups. More pneumonias were reported among patients in the interferon gamma-1b group, but the incidence of severe or life-threatening respiratory tract infections was similar in the two groups.\n In a well-defined population of patients with idiopathic pulmonary fibrosis, interferon gamma-1b did not affect progression-free survival, pulmonary function, or the quality of life. Owing to the size and duration of the trial, a clinically significant survival benefit could not be ruled out.\n Copyright 2004 Massachusetts Medical Society", "Idiopathic pulmonary fibrosis is a fatal disease for which no effective treatment exists. We assessed whether treatment with interferon gamma-1b improved survival compared with placebo in patients with idiopathic pulmonary fibrosis and mild-to-moderate impairment of pulmonary function.\n 826 patients with idiopathic pulmonary fibrosis were enrolled from 81 centres in seven European countries, the USA, and Canada. Patients were randomly assigned (double-blind) in a 2:1 ratio to receive 200 microg interferon gamma-1b (n=551) or equivalent placebo (n=275) subcutaneously, three times per week. Eligible patients were aged 40-79 years, had been diagnosed in the past 48 months, had a forced vital capacity of 55-90% of the predicted value, and a haemoglobin-corrected carbon monoxide diffusing capacity of 35-90% of the predicted value. The primary endpoint was overall survival time from randomisation measured at the second interim analysis, when the proportion of deaths had reached 75% of those expected by the study conclusion. This study is registered with ClinicalTrials.gov, number NCT00075998.\n At the second interim analysis, the hazard ratio for mortality in patients on interferon gamma-1b showed absence of minimum benefit compared with placebo (1.15, 95% CI 0.77-1.71, p=0.497), and indicated that the study should be stopped. After a median duration of 64 weeks (IQR 41-84) on treatment, 80 (15%) patients on interferon gamma-1b and 35 (13%) on placebo had died. Almost all patients reported at least one adverse event, and more patients on interferon gamma-1b group had constitutional signs and symptoms (influenza-like illness, fatigue, fever, and chills) than did those on placebo. Occurrence of serious adverse events (eg, pneumonia, respiratory failure) was similar for both treatment groups. Treatment adherence was good and few patients discontinued treatment prematurely in either group.\n We cannot recommend treatment with interferon gamma-1b since the drug did not improve survival for patients with idiopathic pulmonary fibrosis, which refutes previous findings from subgroup analyses of survival in studies of patients with mild-to-moderate physiological impairment of pulmonary function.\n InterMune.", "Twenty-six symptomatic subjects with clinical evidence plus either high-resolution computed tomography (HRCT, n = 25) or open-lung biopsy (OLB, n = 1) patterns typical for idiopathic usual interstitial pneumonia (idiopathic UIP) were entered into a randomized prospective treatment trial using high-dose prednisone (n = 12) versus colchicine (n = 14). The minimum dose of prednisone used was 60 mg/d for 1 mo, tapered to 40 mg/d over the second month, tapered to 40 mg every other day during the third month, with subsequent doses adjusted as clinically indicated. The dose of colchicine was 0.6-1.2 mg/d, as tolerated. The presence of a rim of subpleural honeycomb change was present in all of the 25 subjects who had HRCT. Subjects treated with high-dose prednisone alone experienced a higher incidence of serious side effects and also exhibited a trend (not statistically significant, p = 0.391) to more rapid decline of pulmonary function and shortened survival than did those treated with colchicine alone. In most subjects with typical clinical and HRCT features of idiopathic UIP, neither prednisone nor colchicine resulted in objective improvement, and the disease continued to progress in the majority. Colchicine appears to be a safer alternative to a trial of high-dose prednisone but may be no different than no therapy.", "Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no known efficacious therapy. Imatinib is a tyrosine kinase inhibitor with potential efficacy to treat fibrotic lung disease.\n To investigate the safety and clinical effects of imatinib in patients with IPF.\n We studied 119 patients in an investigator-initiated, multicenter, multinational, double-blind clinical trial to receive imatinib or placebo for 96 weeks.\n Over 96 weeks of follow-up, imatinib did not differ significantly from placebo (log rank P = 0.89) for the primary endpoint defined as time to disease progression (10% decline in percent predicted FVC from baseline) or time to death. There was no effect of imatinib therapy on change in FVC at 48, 72, or 96 weeks (P > or = 0.39 at all time points) or change in diffusing capacity of carbon monoxide at 48, 72, or 96 weeks (P > or = 0.26 at all time points). Change in resting Pa(O(2)) favored imatinib therapy at 48 weeks (P = 0.005) but not at 96 weeks (P = 0.074). During the 96-week trial there were 8 deaths in the imatinib group and 10 deaths in the placebo group (log rank test P = 0.64). Thirty-five (29%) patients discontinued the study without reaching the primary endpoint (imatinib, 32%; placebo, 27%; P = 0.51). Serious adverse events (SAEs) were not more common in the imatinib group (imatinib, 18 SAEs in 17 patients; placebo, 19 SAEs in 18 patients).\n In a randomized, placebo-controlled trial of patients with mild to moderate IPF followed for 96 weeks, imatinib did not affect survival or lung function. Clinical trial registered with www.clinicaltrials.gov (NCT00131274).", "Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease without proven effective therapy. A multicentre, double-blind, placebo-controlled, randomised phase III clinical trial was conducted in Japanese patients with well-defined IPF to determine the efficacy and safety of pirfenidone, a novel antifibrotic oral agent, over 52 weeks. Of 275 patients randomised (high-dose, 1,800 mg x day(-1); low-dose, 1,200 mg x day(-1); or placebo groups in the ratio 2:1:2), 267 patients were evaluated for the efficacy of pirfenidone. Prior to unblinding, the primary end-point was revised; the change in vital capacity (VC) was assessed at week 52. Secondary end-points included the progression-free survival (PFS) time. Significant differences were observed in VC decline (primary end-point) between the placebo group (-0.16 L) and the high-dose group (-0.09 L) (p = 0.0416); differences between the two groups (p = 0.0280) were also observed in the PFS (the secondary end-point). Although photosensitivity, a well-established side-effect of pirfenidone, was the major adverse event in this study, it was mild in severity in most of the patients. Pirfenidone was relatively well tolerated in patients with IPF. Treatment with pirfenidone may decrease the rate of decline in VC and may increase the PFS time over 52 weeks. Additional studies are needed to confirm these findings.", "Twenty-seven newly diagnosed patients with idiopathic pulmonary fibrosis (IPF) who were previously untreated for IPF were enrolled in a prospective, double-blind, randomized, placebo-controlled study to compare the therapeutic effect of combined prednisone/azathioprine (n = 14) with prednisone plus placebo (n = 13). Prednisone was started at 1.5 mg/kg/day (not to exceed 100 mg/day) for the first 2 wk followed by a biweekly taper to a maintenance dose of 20 mg/day. Azathioprine was administered at a daily dose of 3 mg/kg (not to exceed 200 mg/day). The patients tolerated the use of azathioprine well with few associated side effects. Changes in lung function at 1 yr, as measured by resting alveolar-arterial oxygen difference P[A-a]O2, FVC, and single breath diffusing capacity for carbon monoxide (DLCOSB), were all somewhat better in the azathioprine/prednisone group compared with the prednisone alone group, although none of these comparisons were statistically significant. Six of 14 (43%) patients randomized to prednisone plus azathioprine died during the 9-yr follow-up period, compared with 10 of 13 (77%) patients randomized to prednisone plus placebo. A Cox model survival analysis shows a nonsignificant but potentially large survival advantage for azathioprine/prednisone (hazard ratio 0.48, with 95% confidence interval increasing from 0.17 to 1.38). When adjusted for age, the survival advantage of azathioprine/prednisone becomes marginally significant (hazard ratio 0.26, with 95% confidence interval increasing from 0.08 to 0.88; p = 0.02 by large sample approximation, p = 0.05 by randomization test). We conclude that combined prednisone and azathioprine is a safe and possibly effective regimen for the treatment of IPF.(ABSTRACT TRUNCATED AT 250 WORDS)", "In a randomised, controlled study alternate day prednisolone with an initial high dose phase (\"prednisolone only series\") has been compared with cyclophosphamide plus alternate day low dose prednisolone (\"cyclophosphamide-prednisolone series\") in 43 patients with previously untreated fibrosing alveolitis (five patients had received prednisolone in minimal dosage). In the prednisolone only series prednisolone 60 mg daily was given for one month and then reduced by 5 mg a week to 20 mg on alternate days or the minimum dose to maintain early improvement. Patients in the cyclophosphamide-prednisolone series received 100, 110, or 120 mg cyclophosphamide daily (depending on body weight) plus 20 mg prednisolone on alternate days. Treatment was continued indefinitely, or changed to the alternative regimen if the patient deteriorated, failed to improve, or developed drug toxicity. For response to treatment (as judged by change in breathlessness score, radiographic appearance, and lung function) patients were classified as improved, stable, or deteriorating. Deaths from cryptogenic fibrosing alveolitis were also analysed. Improvement had occurred at one or more assessments in seven of the 22 patients in the prednisolone only series and in five of the 21 patients in the cyclophosphamide-prednisolone series. At three years, however, only two of the 22 patients in the prednisolone only series were still improved and three stable, compared with one and seven of the 21 patients in the cyclophosphamide-prednisolone series (three of the seven had stopped treatment because of toxicity). Life table analysis suggested better survival in patients in the cyclophosphamide-prednisolone series but this was not significant. At three years 10 of 22 patients in the prednisolone only series had died compared with three of 21 patients in the cyclophosphamide-prednisolone series. With death or failure of first treatment regimen as outcome there was a significant advantage to the patients having cyclophosphamide-prednisolone. This advantage was explained in part by the better lung volumes in this group on admission. After allowance had been made for total lung capacity (TLC), no other factor was predictive of outcome. Analyses of subgroups according to TLC on admission showed that patients with a TLC below 60% predicted did badly and those with a TLC of 80% or more predicted did well with both regimens. Patients with an initial TLC of 60-79% predicted did better with the cyclophosphamide-prednisolone regimen. Side effects were uncommon in both series and those due to cyclophosphamide resolved when treatment was stopped. The combination of cyclophosphamide with prednisolone may be an alternative to prednisolone alone with an initial high dose phase. Many patients, however, failed to respond to either treatment." ]

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[ "Ulcer prevention in long-term users of nonsteroidal anti-inflammatory drugs: results of a double-blind, randomized, multicenter, active- and placebo-controlled study of misoprostol vs lansoprazole.", "Effect of ranitidine on gastroduodenal mucosal damage induced by nonsteroidal antiinflammatory drugs.", "Misoprostol and ranitidine in the prevention of NSAID-induced ulcers: a prospective, double-blind, multicenter study.", "Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens.", "Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine.", "Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized, controlled trial.", "Famotidine for healing and maintenance in nonsteroidal anti-inflammatory drug-associated gastroduodenal ulceration.", "Misoprostol coadministered with diclofenac for prevention of gastroduodenal ulcers. A one-year study.", "A controlled study comparing the effects of nabumetone, ibuprofen, and ibuprofen plus misoprostol on the upper gastrointestinal tract mucosa.", "Nonsteroidal antiinflammatory drugs for cancer pain: comparison between misoprostol and ranitidine in prevention of upper gastrointestinal damage.", "Ranitidine prevents duodenal ulcers associated with non-steroidal anti-inflammatory drug therapy.", "[Misoprostol in the prevention of gastric erosions caused by nonsteroidal anti-inflammatory agents].", "Misoprostol prevents NSAID-induced gastroduodenal lesions in patients with osteoarthritis and rheumatoid arthritis.", "Effect of ranitidine on gastroduodenal mucosal damage in patients on long-term non-steroidal anti-inflammatory drugs.", "Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group.", "A double-blind comparison of the gastroduodenal safety and efficacy of diclofenac and a fixed dose combination of diclofenac and misoprostol in the treatment of rheumatoid arthritis.", "Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group.", "Primary gastroduodenal prophylaxis with omeprazole for non-steroidal anti-inflammatory drug users.", "Prevention of peptic ulcer and dyspeptic symptoms with omeprazole in patients receiving continuous non-steroidal anti-inflammatory drug therapy. A Nordic multicentre study.", "Helicobacter pylori infection, ABO blood group, and effect of misoprostol on gastroduodenal mucosa in NSAID-treated patients with rheumatoid arthritis.", "Double-blind comparison of efficacy and gastroduodenal safety of diclofenac/misoprostol, piroxicam, and naproxen in the treatment of osteoarthritis.", "Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial.", "Diclofenac/misoprostol compared with diclofenac in the treatment of osteoarthritis of the knee or hip: a randomized, placebo controlled trial. Arthrotec Osteoarthritis Study Group.", "Nizatidine prevents peptic ulceration in high-risk patients taking nonsteroidal anti-inflammatory drugs.", "The gastroduodenal safety and efficacy of the fixed combination of diclofenac and misoprostol in the treatment of osteoarthritis.", "Ranitidine protects against gastroduodenal mucosal damage associated with chronic aspirin therapy.", "Double blind, placebo controlled trial on the cytoprotective effect of misoprostol in subjects with rheumatoid arthritis, osteoarthritis and seronegative spondarthropathy on NSAIDs.", "Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial.", "High-dose ranitidine for the prevention of recurrent peptic ulcer disease in rheumatoid arthritis patients taking NSAIDs.", "Efficacy and tolerability of pantoprazole compared with misoprostol for the prevention of NSAID-related gastrointestinal lesions and symptoms in rheumatic patients.", "Efficacy of pantoprazole in the prevention of peptic ulcers, induced by non-steroidal anti-inflammatory drugs: a prospective, placebo-controlled, double-blind, parallel-group study.", "The effect of ranitidine on NSAID related dyspeptic symptoms with and without peptic ulcer disease of patients with rheumatoid arthritis and osteoarthritis.", "Randomized trial of low-dose misoprostol and naproxen vs. nabumetone to prevent recurrent upper gastrointestinal haemorrhage in users of non-steroidal anti-inflammatory drugs.", "Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial.", "Nizatidine in therapy and prevention of non-steroidal anti-inflammatory drug-induced gastroduodenal ulcer in rheumatic patients.", "A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group.", "Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs.", "Cimetidine therapy in nonsteroidal anti-inflammatory drug gastropathy. Double-blind long-term evaluation.", "Lansoprazole reduces ulcer relapse after eradication of Helicobacter pylori in nonsteroidal anti-inflammatory drug users--a randomized trial.", "Efficacy of 12 months' misoprostol as prophylaxis against NSAID-induced gastric ulcers. A placebo-controlled trial." ]

[ "Studies that report prevention of ulcer recurrence among long-term users of nonsteroidal anti-inflammatory drugs (NSAIDs) that do not stratify for Helicobacter pylori status may not be generalizable to the large population of individuals without H pylori.\n This was a prospective, double-blind, multicenter, active- and placebo-controlled study among 537 patients without H pylori who were long-term users of NSAIDs and who had a history of endoscopically documented gastric ulcer. Patients were randomized to receive placebo, 200 microg of misoprostol 4 times a day, or 15 or 30 mg of lansoprazole once daily for 12 weeks. Ulcer status was determined by endoscopy at 4, 8, and 12 weeks.\n Patients receiving lansoprazole (15 or 30 mg) remained free from gastric ulcer longer than those who received placebo (P<.001) but for a shorter time than those who received misoprostol. By week 12, the percentages of gastric ulcer-free patients were as follows: placebo, 51% (95% confidence interval [CI], 41.1%-61.3%); misoprostol, 93% (95% CI, 87.2%-97.9%); 15-mg lansoprazole, 80% (95% CI, 72.5%-87.3%); and 30-mg lansoprazole, 82% (95% CI, 75.0%-89.6%). A significantly higher proportion of patients in the misoprostol group reported treatment-related adverse events and early withdrawal from the study. When the impact of withdrawals on ulcer development was considered (as failures), therapy was successful for 69% for each of the active treatment groups and 35% for the placebo group.\n Proton pump inhibitors such as lansoprazole are superior to placebo for the prevention of NSAID-induced gastric ulcers but not superior to misoprostol, 800 microg/d. When the poor compliance and potential adverse effects associated with misoprostol are considered, proton pump inhibitors and full-dose misoprostol are clinically equivalent.", "The effect of ranitidine in preventing mucosal damage caused by nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated for eight weeks in a prospective study of 144 patients requiring NSAIDs. Patients with normal endoscopic findings were randomly assigned to receive either ranitidine 150 mg twice daily or placebo for eight weeks, along with either ibuprofen, indomethacin, naproxen, sulindac, or piroxicam. Duodenal damage was significantly less in the ranitidine group compared with the placebo group by weeks 4 and 8 (P less than or equal to 0.01). Duodenal ulcers did not develop in any patients on ranitidine (0/57) compared with 4/49 patients (8%) on placebo (P = 0.02). No significant difference was found between treatment groups with respect to gastric damage; 6/60 (10%) in the ranitidine group compared with 6/50 (12%) in the placebo group developed gastric ulcers. These findings suggest that acid suppression is of greater importance for mucosal protection in the duodenum than in the stomach, where other defense mechanisms may be operative. While ranitidine is an effective prophylaxis for NSAID-induced damage in the duodenum, further studies are needed to define specific risk groups and to assess the potential usefulness of more complete acid suppression in preventing gastric mucosal damage.", "To compare ranitidine to misoprostol with respect to the prevention of gastric and duodenal ulcers in patients on chronic NSAID therapy.\n A multi-center, 8-wk, randomized, double-blind study. Eligible patients were on chronic NSAID therapy and were experiencing NSAID-related upper gastrointestinal (UGI) pain without UGI endoscopic evidence of gastric or duodenal ulcers. Patients enrolled in the study were randomized to either misoprostol 200 micrograms q.i.d. or ranitidine 150 mg b.i.d.. Follow-up UGI endoscopy was performed after 4 and 8 wk of treatment. Therapeutic failure was considered the development of a gastric or duodenal ulcer > or = 0.3 cm in diameter with perceptible depth.\n Gastric ulcers were found in only 1/180 (0.56%) patient on misoprostol and in 11/194 (5.67%) patients on ranitidine, a difference that was statistically significant (p < 0.01). Duodenal ulcer rates were similar for the ranitidine (2/185 or 1.08%) and misoprostol (2/181 or 1.10%) groups.\n Misoprostol is significantly more effective than ranitidine in the prevention of NSAID-induced gastric ulcers. Ranitidine was as effective as misoprostol for the prevention of NSAID-induced duodenal ulcers. Misoprostol should be used for prophylaxis against both gastric and duodenal ulceration in patients on chronic NSAID therapy.", "To compare the effectiveness and tolerability of three misoprostol dosing regimens for the prevention of gastric and duodenal ulcers associated with long-term nonsteroidal anti-inflammatory drug (NSAID) therapy.\n A multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel, four-limb study.\n Eligibility criteria included upper gastrointestinal symptoms during NSAID therapy and no endoscopic evidence of gastric or duodenal ulcers. A total of 1623 patients was enrolled; 1197 of these met major accession and regimen-compliance criteria and completed the trial. These 1197 patients composed the evaluable group.\n Patients were randomly assigned to one of four regimens: placebo four times daily; 200 micrograms of misoprostol twice daily and placebo twice daily; 200 micrograms of misoprostol three times daily and placebo once daily; and 200 micrograms of misoprostol four times daily.\n Upper gastrointestinal endoscopic examinations for ulcers were done after 4, 8, and 12 weeks of therapy. Tolerability and safety of the regimens were assessed by adverse-event monitoring.\n In the placebo group, the incidence of gastric ulcers was 15.7% and the incidence of duodenal ulcers was 7.5%. The incidence of gastric ulcers was significantly lower in the groups receiving misoprostol twice daily (8.1%; difference, 7.6% [95% CI, 2.7% to 12.5%]; P = 0.002), three times daily (3.9%; difference, 11.8% [CI, 7.4% to 16.3%]; P < 0.001), and four times daily (4%; difference, 11.7% [CI, 6.7% to 16.8%]; P < 0.001) compared with placebo. The gastric ulcer rate was significantly higher in patients receiving misoprostol twice daily compared with those receiving misoprostol three times daily (difference, 4.2% [95% CI, 0.7% to 7.7%]; P = 0.02). A significant (P = 0.02) misoprostol dose-response effect was noted in the prevention of gastric ulcers. The incidence of duodenal ulcers was significantly lower in the groups receiving misoprostol twice daily (2.6%; difference, 4.9% [CI, 1.5% to 8.2%]; P = 0.004), three times daily (3.3%; difference, 4.2% [CI, 0.6% to 7.7%]; P = 0.019), and four times daily (1.4%; difference, 6.1% [CI, 2.6% to 9.6%]; P = 0.007) compared with placebo. No significant difference was detected between patients receiving misoprostol twice daily and those receiving misoprostol three times daily, and no dose-response effect was noted with duodenal ulcers. The incidence of withdrawals for adverse events was significantly lower in the groups receiving misoprostol twice daily (12%) and three times daily (12%) than in the group receiving it four times daily (20%). The incidence of gastrointestinal adverse events was significantly higher in the group receiving misoprostol four times daily (74%) than in the placebo group (62%).\n Misoprostol, 200 micrograms twice or three times daily, offers substantial protection against gastric and duodenal ulcers in patients receiving long-term NSAID therapy. These dosages were better tolerated than the currently approved regimen of 200 micrograms four times daily.", "To evaluate the prophylactic effect of ranitidine 150 mg twice daily in patients requiring one of the following non-steroidal anti-inflammatory drugs: naproxen, piroxicam, diclofenac, and indomethacin. In addition, risk factors were studied in order to help in targeting of such treatment to specific groups of patients.\n Double blind, placebo controlled, randomised, parallel group with endoscopic assessments at 0, 4, and 8 weeks.\n Multicentre outpatient study at secondary referral centres in five European countries. PATIENTS--297 patients with rheumatoid arthritis or osteoarthritis over the age of 18 without lesions in the stomach and duodenum at baseline endoscopy (after one week without taking non-steroidal anti-inflammatory drugs). Those taking other antirheumatic agents, concomitant ulcerogenic drugs, or treatment for peptic ulcers within the previous 30 days were excluded. Age, sex, arthritic disease, and type of non-steroidal anti-inflammatory drug used were comparable in the two treatment groups. In all, 263 patients completed the trial.\n Ranitidine 150 mg twice daily or placebo (plus the selected non-steroidal anti-inflammatory drug) was prescribed within five days after the baseline endoscopy for two consecutive periods of four weeks. Paracetamol was permitted during the study, but not antacids. Patients were withdrawn if the most severe grade of damage (including ulceration) was found at the four week endoscopy or when indicated, or with lesser damage at the investigator's discretion.\n Frequency of gastric and duodenal ulceration or lesions, or both.\n The cumulative incidence of peptic ulceration by eight weeks was 10.3% (27/263); 2 out of 135 (1.5%) developed duodenal ulceration in the ranitidine group, compared with 10 out of 126 (8%) taking placebo. The frequency of gastric ulceration was the same (6%) for the two groups at eight weeks. Though significantly fewer gastric lesions developed in the ranitidine group by eight weeks. The frequency of non-ulcerative lesions in the duodenum did not differ greatly for the two groups at either time point. Twelve out of 75 (16%) patients taking piroxicam developed peptic ulceration, of whom two thirds had duodenal ulceration. Patients with a history of peptic ulcer were particularly susceptible to recurrent ulceration, against which ranitidine offered some protection.\n Ranitidine 150 mg twice daily significantly reduced the incidence of duodenal ulceration but not gastric ulceration when prescribed concomitantly with one of four commonly used non-steroidal anti-inflammatory drugs.", "To compare the efficacy and frequency of adverse experiences of misoprostol and sucralfate in the prevention of gastric ulcers in patients receiving nonsteroidal anti-inflammatory drug (NSAID) therapy.\n A prospective, randomized, single-blind, multicenter trial.\n Patients with osteoarthritis receiving treatment with ibuprofen, piroxicam, or naproxen and experiencing abdominal pain were eligible.\n Patients who were expected to receive at least 3 months of NSAID therapy and who did not have a gastric ulcer at the time of the initial screening endoscopy were randomized to receive misoprostol, 200 micrograms four times a day, or sucralfate, 1 g four times a day. A gastric ulcer was defined as a lesion of the gastric mucosa 0.3 cm or greater in diameter. Patients were followed clinically, and repeat endoscopies were performed after 4, 8, and 12 weeks.\n The development of a gastric ulcer, which was regarded as a prophylaxis failure.\n Two hundred fifty-three patients were evaluable for efficacy analysis. A gastric ulcer developed in 2 of the 122 (1.6%, 95% CI, 0.3% to 6.4%) patients on misoprostol, compared with 21 of 131 patients on sucralfate (16%, CI, 10.4% to 23.7%). The difference in ulcer rates was 14.4% (CI, 10.4% to 19.5%; P less than 0.001).\n In patients receiving chronic NSAID therapy for osteoarthritis, treatment with misoprostol for 3 months was associated with a significantly lower frequency of gastric ulcer formation, compared with treatment with sucralfate (P less than 0.001).", "Nonsteroidal anti-inflammatory drugs (NSAIDs) are strongly associated with gastroduodenal ulceration. How to manage patients with NSAID-associated ulcers is a common clinical dilemma. High-dose famotidine in the healing and maintenance of NSAID-associated gastroduodenal ulceration was therefore evaluated.\n One hundred four patients with rheumatoid or osteoarthritis who had gastroduodenal ulceration received famotidine, 40 mg twice daily. Sixteen patients stopped and 88 continued their NSAID treatment. Ulcer healing was assessed endoscopically at 4 and 12 weeks. Seventy-eight NSAID users with healed ulcers were then randomized to receive 40 mg twice daily famotidine or placebo and underwent endoscopy at 4, 12, and 24 weeks.\n Cumulative ulcer healing rates at 12 weeks were 89.0% (95% confidence interval [CI], 82.3%-95.7%) for patients who continued NSAID treatment and 100% (95% CI, 82.9%-100.0%) for those who stopped. The subsequent estimated cumulative gastroduodenal ulcer relapse over 6 months for NSAID users who took placebo was 53.5% (95% CI, 36.6%-70.3%). This was reduced to 26.0% (12.1%-39.9%) in patients taking famotidine (P = 0.011).\n High-dose famotidine is effective ulcer healing therapy in patients who stop or continue NSAID treatment and significantly reduced the cumulative incidence of gastroduodenal ulcer recurrence compared with placebo when given as maintenance therapy.", "The objective of this study was to determine the long-term efficacy of misoprostol in preventing diclofenac-induced gastroduodenal ulcers in rheumatoid arthritis and osteoarthritis patients. Three hundred eighty-four patients who had an endoscopically confirmed gastric or duodenal lesion that had healed with misoprostol therapy were randomized to receive misoprostol or placebo coadministered with diclofenac for up to 52 weeks. Endoscopic examinations were repeated at weeks 12, 24, and 52. The development of a gastric and/or duodenal ulcer was considered a prophylaxis failure. Results in the evaluable cohort of patients demonstrated that gastroduodenal ulcer incidences were lower with misoprostol than placebo for all study periods (0-12 weeks, 7% vs 23%; 0-24 weeks, 11% vs 26%; and 0-52 weeks, 15% vs 31%). Misoprostol did not interfere with the antiarthritic effects of diclofenac. In conclusion, misoprostol coadministered with diclofenac for 12 months to patients with rheumatoid arthritis or osteoarthritis significantly reduced the incidence of diclofenac-induced gastroduodenal ulcers (P < or = 0.018).", "This study was developed to compare the incidence of endoscopically diagnosed ulcers in elderly patients taking nabumetone, ibuprofen, or concomitant ibuprofen/misoprostol. Further research is indicated to better establish the clinical relevance of these endoscopy findings.\n We conducted a prospective, multicenter, randomized, endoscopist-blinded, 12-week study involving 171 patients with osteoarthritis aged 60 years and older. Patients were randomized to receive nabumetone, 1000 mg (n = 58); ibuprofen, 600 mg four times daily (n = 53); or ibuprofen, 600 mg four times daily, administered concomitantly with misoprostol, 200 micrograms four times daily (n = 60). Endoscopy was performed at baseline and at weeks 2, 6, and 12. Endoscopy results were scored on a scale of 1 to 9. Significant ulcers were defined as breaks in the mucosa greater than 5 mm with appreciable depth.\n Of the 171 randomized patients, 148 completed the study. There was no significant difference in the incidence of significant ulcers between the nabumetone group and the ibuprofen/misoprostol group (one vs zero). There were significantly fewer significant ulcers in the nabumetone and ibuprofen/misoprostol groups than in the ibuprofen monotherapy group (one and zero vs eight; P < .01). There also was a significant difference in the time to ulcer development, with a greater risk of developing an ulcer sooner with ibuprofen treatment (P < .01) than either nabumetone or ibuprofen/misoprostol treatment. The severity of osteoarthritis, based on physicians' assessments, improved in 64% of patients in the nabumetone group, 55% of those in the ibuprofen group, and 63% of those in the ibuprofen/misoprostol group.\n Nabumetone is equivalent in ulcerogenicity to concomitant ibuprofen/misoprostol and is significantly less ulcerogenic than ibuprofen alone.", "The prophylactic strategy of nonsteroidal antiinflammatory drug (NSAID)-induced upper gastrointestinal (UGI) damage has largely been studied in arthritic patients, but not in cancer patients. The efficacy of misoprostol and ranitidine in the prevention of gastroduodenal damage in patients taking diclofenac for their cancer pain has been compared in this study.\n Patients who needed high-dose (200 to 300 mg/d) diclofenac for cancer pain and without mucosal lesions at baseline gastroduodenal endoscopy were randomized to receive misoprostol (200 micrograms twice daily; M group) or ranitidine (150 mg twice daily; R group). UGI endoscopy was repeated after 4 weeks.\n Twenty-three patients treated with misoprostol and 26 treated with ranitidine concluded the study. The M group showed a significantly (P < .02) lower incidence of gastroduodenal lesions (two patients; 8.7%) than the R group (10 patients; 38.5%). Gastric ulcers occurred in one (4%) misoprostol-treated patient and in six (23%) ranitidine-treated patients. Six of seven patients with ulcers were asymptomatic. Seventy-one percent and 86% of ulcers occurred in patients older than 60 years and in those who received greater than 3.1 mg/kg of diclofenac, respectively.\n Misoprostol was significantly more effective than ranitidine in the prevention of gastroduodenal lesions in cancer patients receiving diclofenac.", "The results of four similarly designed, randomized, double-blind, placebo-controlled studies conducted to evaluate ranitidine as prophylaxis for NSAID-associated damage are reviewed. A total of 673 patients receiving therapeutic dosages of NSAIDs for arthritic or musculoskeletal conditions also received either ranitidine 150 mg twice daily (n = 343) or placebo (n = 330) for four weeks (two studies) or eight weeks (two studies). Endoscopic grading of mucosal lesions was based on a modified Lanza scoring system. All patients had normal baseline endoscopies. After four weeks of treatment a significant protective effect against duodenal mucosal lesions including duodenal ulcers (three studies) and gastric mucosal lesions including gastric ulcers (one study) was observed in patients who received ranitidine compared with those who received placebo. A meta-analysis of the four studies confirmed that significantly fewer patients receiving ranitidine than placebo developed duodenal ulcers (1% vs. 6%, P = 0.01). Endoscopic data at eight weeks from the two longer-term studies showed that duodenal ulcers occurred in ranitidine- and placebo-treated patients at a rate of 1% (2/137) vs. 8% (10/126) (P = 0.02), respectively, in one trial, and 0% (0/57) vs. 8% (4/49) (P = 0.02), respectively, in the other trial. No protective effect in the stomach was evident at eight weeks. We conclude that ranitidine is effective in preventing NSAID-associated duodenal ulcers and may be appropriate prophylaxis for certain high-risk patients.", "A multicenter, double-blind, placebo-controlled study was carried out to determine whether the synthetic prostaglandin E1 analog misoprostol is effective in preventing gastric and duodenal lesions induced by nonsteroidal anti-inflammatory drugs. Two hundred fifty-six patients under nonsteroidal anti-inflammatory drug treatment (diclofenac, naproxen, piroxicam, ibuprofen, indomethacin, ketoprofen, or tiaprofenic acid) for osteoarthritis, rheumatoid arthritis, or other rheumatic diseases were included in the study. None of the patients had patent gastroduodenal damage at entry (0 to 3 mucosal erosions or subepithelial hemorrhages on endoscopy). Patients were randomly assigned to treatment with misoprostol 400 micrograms/d (M 400), misoprostol 800 micrograms/d (M 800) or a placebo. Results of the follow-up endoscopy on day 28 in the 186 evaluable patients showed that gastric erosions were significantly less common (p < or = 0.02) in the two misoprostol groups (5% and 2% in the M 400 and M 800 groups respectively) than in the placebo group (19%). Similar small numbers of patients in the three groups had gastric subepithelial hemorrhages or duodenal lesions. Three patients developed gastric ulcers in the placebo group, versus none in the misoprostol groups. Misoprostol therapy did not modify the efficacy of the nonsteroidal antiinflammatory agent on pain or other rheumatologic manifestations. Diarrhea occurred in 1%, 10%, and 5% of patients in the M 400, M 800, and placebo groups, respectively. In conclusion, misoprostol given in combination with a nonsteroidal anti-inflammatory agent for 28 days significantly reduced the incidence of gastric erosions in a random sample of patients with a variety of rheumatic diseases. The daily dosage associated with the best risk/benefit ratio may be 400 micrograms/day.", "The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant adverse effects on the integrity of the gastrointestinal (GI) mucosa. A unique, double-blind, placebo-controlled, randomized, multicentre study investigated the prophylactic co-therapy with misoprostol, a novel PGE1 analog, for the prevention of the NSAID-induced gastric and duodenal mucosal lesions. The study also investigated whether the co-therapy with misoprostol could interfere with the anti-rheumatic action of the NSAIDs using detailed rheumatological assessments. Patients with osteoarthritis or rheumatoid arthritis had to be free of symptoms and significant erosive and/or haemorrhagic lesions of the upper GI tract. The patients were randomized to co-therapy with misoprostol or its matching placebo. Follow-up endoscopy and symptoms assessment were carried out within 4 weeks and compared to pre-study findings. Misoprostol significantly reduced (p less than 0.01) the incidence of erosive and/or haemorrhagic gastric and duodenal mucosal lesions. Misoprostol also reduced the proportion of patients with epigastric pain (p less than 0.01). Misoprostol was well tolerated and did not interfere with the anti-rheumatic activity of the administered NSAID. We conclude that misoprostol is safe and effective in the protection against NSAID-induced gastric and duodenal mucosal lesions and symptoms.", "Twenty-four patients taking long-term non-steroidal anti-inflammatory drugs (NSAIDs) were followed in a double-blind placebo-controlled trial to assess the effect of ranitidine 300 and 600 mg daily on upper gastrointestinal mucosal damage and to assess methods of monitoring mucosal damage. Sixteen were given ranitidine and 8 had placebo throughout the study. Comparisons suggested that ranitidine reduced symptoms and endoscopic evidence of mucosal damage. Histological evidence of gastritis was present in only half of those on ranitidine but in all receiving placebo. Erosions and blood loss occurred intermittently during the study but faecal blood losses using 51Cr-labelled red cells failed to identify any difference between groups. Endoscopic observation of erosions and serial biopsies may provide simple, reliable measurements for future studies to assess the effect of therapy in reducing mucosal damage from long-term NSAIDs.", "To determine the efficacy of misoprostol for the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced duodenal and gastric ulcers in arthritis patients receiving NSAID therapy.\n A randomized, double-blind, multicenter, placebo-controlled trial.\n Six hundred thirty-eight private, Veterans Affairs, health maintenance, and academic practices.\n Six hundred thirty-eight patients with chronic inflammatory or noninflammatory arthritis who were taking an NSAID but who did not have a gastric or duodenal ulcer on screening endoscopy received treatment with ibuprofen, piroxicam, naproxen, sulindac, tolmetin, indomethacin, or diclofenac daily for 3 months. Four hundred fifty-five (71%) patients completed the trial.\n Patients meeting the entry criteria were randomized to receive either misoprostol, 200 micrograms, or placebo, four times a day for 12 weeks.\n The endoscopy was repeated at 4, 8, and 12 weeks. The development of a duodenal or gastric ulcer (defined as a circumscribed mucosal defect > or = 0.5 cm in diameter and with perceptible depth) was regarded as prophylactic failure.\n By 12 weeks, a duodenal ulcer developed in 2 of 320 (0.6%; 95% CI, 0.2% to 3.9%) patients randomized to receive misoprostol, compared with 15 of 323 (4.6%; CI, 2.8% to 8%) patients receiving placebo (P = 0.002). A gastric ulcer developed in 6 of 320 (1.9%; (CI, 0.8% to 4.4%) patients, compared with in 25 of 323 (7.7%; CI, 5.1% to 11.4%), respectively.\n Misoprostol significantly lowers the frequency of both duodenal and gastric ulcer development in patients who require long-term therapy with NSAIDS.", "This double-blind, parallel group study was conducted to evaluate the gastroduodenal safety and antiarthritic efficacy of a fixed combination of diclofenac sodium 50 mg and misoprostol 200 mcg, compared with a combination of diclofenac 50 mg and placebo. Three hundred and thirty-nine patients with rheumatoid arthritis and no significant gastric or duodenal mucosal damage were enrolled and received study medication (diclofenac/misoprostol, 164; diclofenac/placebo, 175) BID or TID for 12 weeks. Posttreatment gastroduodenal endoscopic examinations revealed ulcers in 11% of the diclofenac/placebo group, compared with only 4% of the diclofenac/misoprostol group (p = 0.034). Four-weekly assessments of arthritic condition revealed no clinically or statistically significant treatment differences. It was concluded that diclofenac/misoprostol caused significantly less gastroduodenal damage than diclofenac, but was as effective as diclofenac alone in the treatment of rheumatoid arthritis.", "Misoprostol is effective for ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) but is often poorly tolerated because of diarrhea and abdominal pain. We compared the efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs.\n In a double-blind study, we randomly assigned 935 patients who required continuous NSAID therapy and who had ulcers or more than 10 erosions in the stomach or duodenum (or both) to receive 20 mg or 40 mg of omeprazole orally in the morning or 200 microg of misoprostol orally four times daily. Patients were treated for four weeks or, in the absence of healing, eight weeks. Treatment success was defined as the absence of ulcers and the presence of fewer than five erosions at each site and not more than mild dyspepsia. We then randomly reassigned 732 patients in whom treatment was successful to maintenance therapy with 20 mg of omeprazole daily, 200 microg of misoprostol twice daily, or placebo for six months.\n At eight weeks, treatment was successful in 76 percent of the patients given 20 mg of omeprazole (233 of 308), 75 percent of those given 40 mg of omeprazole (237 of 315), and 71 percent of those given misoprostol (212 of 298). The rates of gastric-ulcer healing were significantly higher with 20 mg of omeprazole (but not 40 mg of omeprazole) than with misoprostol. Healing rates among patients with duodenal ulcers were higher with either dose of omeprazole than with misoprostol, whereas healing rates among patients with erosions alone were higher with misoprostol. More patients remained in remission during maintenance treatment with omeprazole (61 percent) than with misoprostol (48 percent, P=0.001) and with either drug than with placebo (27 percent, P<0.001). There were more adverse events during the healing phase in the misoprostol group than in the groups given 20 mg and 40 mg of omeprazole (59 percent, 48 percent, and 46 percent, respectively).\n The overall rates of successful treatment of ulcers, erosions, and symptoms associated with NSAIDs were similar for the two doses of omeprazole and misoprostol. Maintenance therapy with omeprazole was associated with a lower rate of relapse than misoprostol. Omeprazole was better tolerated than misoprostol.", "To investigate the efficacy of omeprazole 20 mg o.m. as primary prophylaxis against non-steroidal anti-inflammatory drug (NSAID)-associated ulcer disease or dyspeptic symptoms.\n A parallel group study compared patients randomized to receive omeprazole 20 mg o.m. or placebo as co-therapy with on-going NSAID treatment, over 6 months, in 19 specialist centres in Ireland, Hungary, France, the UK and the USA. One hundred and sixty-nine patients taking NSAIDs regularly, chronically and above defined minimum doses entered the trial. The main outcome measure was the development of gastric or duodenal ulcers detected endoscopically, the development of multiple erosions in the stomach or duodenum, or the onset of moderate or severe dyspeptic symptoms.\n The estimated probability of remaining free of these end-points for 6 months for patients taking omeprazole was 0.78 compared to 0.53 for placebo (P = 0.004). Fourteen patients receiving placebo (16.5%) developed 15 ulcers, comprising nine gastric and six duodenal ulcers, compared to three patients (3.6%) receiving omeprazole (all gastric ulcers). Logistic regression analysis showed that older patients were less likely, whilst those with rheumatoid arthritis were more likely, to remain free of NSAID-associated problems.\n Omeprazole is an effective agent for gastroduodenal prophylaxis in patients taking NSAIDs. Its main effect is to reduce the rate of development of gastric and duodenal ulcers.", "Non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause gastroduodenal lesions and dyspeptic symptoms.\n Patients with a history of dyspepsia or uncomplicated peptic ulcer disease and with a need for continuous NSAID treatment were randomized to receive either 20 mg omeprazole once daily or placebo. Gastroduodenal ulcers, erosions, and dyspeptic symptoms were evaluated after 1 and 3 months.\n During a 3-month study period 4.7% (4 of 85) of omeprazole-treated patients developed peptic ulcer, compared with 16.7% (15 of 90) of patients treated with placebo. This prophylactic effect of omeprazole was sustained independently of previous peptic ulcer history or Helicobacter pylori status. Development of dyspeptic symptoms requiring active treatment, either alone or in combination with ulcer(s) or erosions, occurred in 15.3% (15 of 85) of patients treated with omeprazole and 35.6% of those who received placebo.\n Omeprazole, 20 mg once daily, provides effective prophylactic therapy in patients at risk of developing NSAID-associated peptic ulcers or dyspeptic symptoms.", "Our aim was to investigate the effect of misoprostol on NSAID-induced gastroduodenal mucosal damage in patients with rheumatoid arthritis. The study included 40 patients, and it was designed as a double-blind, placebo-controlled trial. Misoprostol significantly reduced the gastroduodenal mucosal lesions found at endoscopy (P < 0.05) and prevented the development of ulcers. The cumulative incidence of ulcers at four weeks was 5% in the placebo group and 0% in the misoprostol group. The basal and pentagastrin-stimulated acid output as evaluated after 23 days of treatment with misoprostol was not significantly affected. Forty-one percent of the patients had signs of current Helicobacter pylori infection, 33% had positive serology only, and 26% had no evidence of infection. Most of the patients with current infection belonged to blood group O (P < 0.05). Misoprostol treatment did not affect the occurrence of Helicobacter pylori or the rheumatic disease activity. It is concluded that the protective actions of misoprostol on the gastroduodenal mucosa of NSAID-treated patients are largely mediated by mechanisms other than inhibition of acid secretion. The relationship among active Helicobacter pylori infection, blood group O, and peptic ulcer may be helpful to identify a subpopulation of patients taking NSAIDs at risk of developing peptic ulcers.", "To compare the efficacy and gastroduodenal safety of a fixed-dose combination of diclofenac sodium 50 mg and misoprostol 200 micrograms twice daily with those of piroxicam 10 mg twice daily and naproxen 375 mg twice daily in patients with osteoarthritis.\n A 4 week, randomised, double-blind, parallel-group, multicentre study was conducted in 643 patients with symptomatic osteoarthritis of the hip and/or knee, who required continuous non-steroidal anti-inflammatory drug therapy for 4 weeks and who were without significant upper gastrointestinal damage as confirmed by endoscopy.\n For patients who had pre- and post-treatment endoscopic examinations, gastroduodenal ulcers developed in 3 (1.5%) of 200 patients treated with diclofenac/misoprostol, 21 (10.3%) of 204 piroxicam-treated patients, and 17 (8.6%) of 198 patients receiving naproxen (Chi square = 13.771, p = 0.001). The improvement in the osteoarthritis severity index was greater in the diclofenac/misoprostol group than in the piroxicam group (p = 0.004). Changes in physician and patient global assessments showed no significant differences between treatment groups. The incidences of diarrhoea and abdominal pain were higher in the diclofenac/misoprostol group than in the piroxicam and naproxen groups.\n Diclofenac/misoprostol at twice daily dosing is associated with significantly fewer gastroduodenal ulcers than either piroxicam or naproxen. The efficacy of diclofenac/misoprostol in treating the signs and symptoms of osteoarthritis is at least comparable to that of piroxicam and naproxen.", "To investigate whether concurrent administration of misoprostol reduces the occurrence of serious upper gastrointestinal complications, such as perforation, gastric outlet obstruction, or bleeding, in patients with rheumatoid arthritis who are receiving nonsteroidal anti-inflammatory drugs (NSAIDs).\n 6-month randomized, double-blind, placebo-controlled trial.\n 664 clinical practices of family medicine, internal medicine, or rheumatology in the United States and Canada.\n 8843 men and women (mean age, 68 years) receiving continuous therapy with any of 10 specified NSAIDs for control of symptoms of rheumatoid arthritis. Patients were enrolled between July 1991 and August 1993.\n Patients were randomly assigned to receive 200 micrograms of misoprostol or placebo four times a day.\n Development of serious upper gastrointestinal complications detected by clinical symptoms or findings (not by scheduled endoscopy).\n Serious upper gastrointestinal complications were reduced by 40% (odds ratio, 0.598 [95% CI, 0.364 to 0.982; P = 0.049]) among patients receiving misoprostol (25 of 4404 patients) compared with those receiving placebo (42 of 4439 patients). During the first month, more patients receiving misoprostol (20%) than placebo (15%) withdrew from the study, primarily because of diarrhea and related problems (P < 0.001). Risk factors for serious upper gastrointestinal complications were increasing age, history of peptic ulcer or bleeding, and cardiovascular disease. Patients with all four risk factors would have a 9% risk for a major complication in 6 months.\n In older patients with rheumatoid arthritis, misoprostol reduced serious NSAID-induced upper gastrointestinal complications by 40% compared with placebo.", "Gastric (GU) and duodenal ulcers (DU) are common adverse effects of nonsteroidal anti-inflammatory drugs (NSAID). Endoscopically diagnosed upper gastrointestinal (GI) ulceration occurs in about 24% of longterm NSAID users. Coadministration of misoprostol with the NSAID reduces the incidence of NSAID induced GU and DU and their complications. However, compliance is limited by the different dosing regimens of misoprostol and NSAID and GI symptoms associated with misoprostol at its recommended q.i.d. dose. We compared the efficacy, safety, and incidence of endoscopic upper GI ulceration associated with the administration of 2 combinations of diclofenac (50 or 75 mg) and misoprostol 200 microg (D50/M200 t.i.d., D75/M200 b.i.d.), diclofenac 75 mg b.i.d., and placebo in a 6 week, randomized, double blind study in patients with osteoarthritis (OA) of the knee or hip.\n A total of 572 patients with symptomatic OA of the knee or hip and history of GU, DU. or 10 or more erosions were randomized to receive D50/M200 t.i.d., D75/M200 b.i.d., diclofenac 75 mg b.i.d., or placebo for 6 weeks. Arthritis assessments were performed at baseline, 2, and 6 weeks, and upper GI endoscopies at baseline and end of treatment.\n All active treatment groups were significantly better than placebo, at all visits, in improving OA symptoms. There were no significant differences in arthritis efficacy between the diclofenac/ misoprostol combinations and diclofenac. However, endoscopically diagnosed GU and/or DU were significantly less frequent in patients receiving D50/M200 t.i.d. (8%), D75/M200 b.i.d. (7%), and placebo (4%) compared to diclofenac 75 mg b.i.d. (17%). Adverse events were not different between the active treatment groups, except for higher incidences of flatulence with D75/M200 and diarrhea with D50/M200.\n Diclofenac 50 mg/misoprostol 200 microg t.i.d. and diclofenac 75 mg/misoprostol 200 microg b.i.d. are as efficacious as diclofenac 75 mg b.i.d. in the treatment of OA, but are associated with a significantly lower incidence of gastric and/or duodenal ulcers.", "Nonsteroidal anti-inflammatory drug (NSAID) use is increasingly recognized as a major factor associated with peptic ulcer disease and complications. We undertook a multicenter, double-blind, placebo-controlled trial to evaluate efficacy and safety of nizatidine in preventing ulcer formation in patients with osteoarthritis who were taking NSAIDs.\n After endoscopy to rule out the presence of an acute ulcer, 496 patients were randomized to receive nizatidine, 150 mg twice daily (248 patients) or placebo (248 patients) for 3 months. Repeated endoscopies were performed monthly. We defined failure as development of a peptic ulcer (> or = 0.3 cm in diameter).\n Baseline characteristics tested were comparable for the two groups with regard to age, sex, ulcer history, and Helicobacter pylori status. Overall ulcer occurrence in the nizatidine group (9.7%) was not significantly different from that in the placebo group (13.7%; P = .163). High-risk subgroups (patients with ulcer history and patients > or = 65 years of age), however, revealed statistically fewer ulcers for patients receiving nizatidine (P = .035 and P = .042, respectively). Analysis of antacid use showed significantly less use in nizatidine recipients, although there were similar percentages of patients showing improvement in dyspeptic symptoms in each treatment group. We failed to observe a conclusive correlation between H pylori status at baseline, as measured by serum immunoglobulin antibody, and development of an ulcer.\n This study showed that nizatidine, 150 mg, twice daily, significantly reduces the incidence of ulcer formation in high-risk patients taking long-term NSAID therapy. It also relieves NSAID-associated dyspeptic symptoms in some patients.", "A double-blind, randomized, parallel group study was conducted to compare the gastroduodenal safety and antiarthritic efficacy of a fixed combination of diclofenac 50 mg and misoprostol 200 micrograms with that of a combination of diclofenac 50 mg and placebo in patients with osteoarthritis. Three hundred and sixty-one patients with no significant gastroduodenal lesions were enrolled and received study medication two or three times daily for 4 weeks. Post-treatment endoscopic examination of the gastroduodenal mucosa revealed ulcers in 4% of patients in the diclofenac/placebo group compared with none in the diclofenac/misoprostol group (P = 0.015). There were no clinically or statistically significant differences between the two treatment groups in formal assessments of osteoarthritis after either 2 or 4 weeks. It was concluded that diclofenac/misoprostol was associated with significantly less gastroduodenal damage than diclofenac, whilst being as effective as diclofenac alone in the treatment of osteoarthritis.", "A randomized, double-blind, placebo-controlled study examined whether concomitant administration of ranitidine could protect against the gastroduodenal mucosal damage associated with long-term aspirin therapy in healthy men. Twenty-four subjects received ranitidine (150 mg twice daily) plus aspirin (650 mg four times daily), and 19 received placebo twice daily plus aspirin (650 mg four times daily) for four weeks. Gastric injury and duodenal injury were assessed separately according to a numerical rating scale for incidence and severity of lesions observed during endoscopic examinations at baseline and after four weeks of treatment. The ranitidine/aspirin group had significantly less mucosal damage in the stomach and duodenum than the placebo/aspirin group. Mean serum salicylate levels were similar between treatment groups after two and four weeks of aspirin therapy. Therefore, the protective effect of ranitidine was achieved with no compromise in salicylate absorption.", "Ninety arthritic patients were randomly allotted to receive misoprostol 200 micrograms thrice daily or placebo, for 4 weeks, while they were started on various NSAIDs. While upper gastrointestinal symptoms occurred equally in both groups, patients on placebo had significantly more post-therapy abnormal endoscopy findings. Misoprostol was well tolerated without any adverse side effects; it did not interfere with the therapeutic efficacy of the NSAIDs. Arthritic patients requiring long term NSAID therapy appear to benefit from misoprostol because of its cytoprotective effect on the gastrointestinal mucosa.", "The gastric safety of cyclooxgenase-2 inhibitors and prophylactic antisecretory therapy in high-risk arthritis patients is unclear. We studied the ulcer incidence and factors predicting ulcer recurrence in a prospective, double-blinded trial.\n We studied patients who presented with nonsteroidal anti-inflammatory drug-associated ulcer bleeding. After ulcer healing, patients who were negative for Helicobacter pylori were randomly assigned to celecoxib 200 mg twice a day plus omeprazole placebo once daily or diclofenac 75 mg twice daily plus omeprazole 20 mg once daily for 6 months. Patients underwent endoscopy if they developed recurrent bleeding. Those without recurrent events underwent endoscopy at their last follow-up visit.\n Two hundred eighty-seven patients were enrolled; 24 had recurrent gastrointestinal complications. Among 259 patients without events, 222 underwent endoscopy (116 received celecoxib and 106 received diclofenac plus omeprazole). The probability of recurrent ulcers in 6 months was 18.7% in the celecoxib group and 25.6% in the diclofenac plus omeprazole group (difference, -6.7%; 95% CI: -17.8% to 3.9%) (P = 0.21). Combining bleeding and endoscopic ulcers, 24.1% in the celecoxib group and 32.3% in the diclofenac plus omeprazole group had recurrent ulcers in 6 months (difference, -8.2%; 95% CI: -19.5% to 2.9%) (P = 0.15). Treatment-induced significant dyspepsia (hazard ratio, 5.3; 95% CI: 2.6-10.8), age > or =75 (hazard ratio, 2.0; 95% CI: 1.1-3.5), and comorbidity (hazard ratio, 2.1; 95% CI: 1.2-3.7) independently predicted ulcer recurrence.\n Among patients with previous ulcer bleeding, neither celecoxib nor diclofenac plus omeprazole adequately prevents ulcer recurrence. Treatment-induced significant dyspepsia is an indication for endoscopic evaluation.", "Continuous therapy with low-dose ranitidine (150 mg b.d.) is known to be effective for the prevention of recurrent nonsteroidal anti-inflammatory drug (NSAID)-associated duodenal ulcer but not for gastric ulcer.\n To investigate, in a double-blind placebo-controlled study, the preventive effect of a high dose of ranitidine (300 mg b.d.) on the recurrence of both duodenal ulcers and gastric ulcers in rheumatoid arthritis patients with a continuous need for NSAIDs.\n Rheumatoid arthritis patients with a history of peptic ulcer disease were randomized to receive either ranitidine 300 mg b.d. or placebo for 12 months. Endoscopy was performed at study entry and after 6 and 12 months. End-point was the recurrence of gastric or duodenal ulcers.\n The study was stopped after a blinded interim analysis; at that time 10 of the 15 included patients in each treatment group were evaluable. Recurrent duodenal ulcers had occurred in four patients treated with placebo and none of the patients treated with ranitidine (Fisher's exact one-tailed P = 0.04; 95% CI, - 0.70 to -0.10). Recurrent gastric ulcers had occurred in six patients in the placebo group and three patients in the ranitidine group (Fisher's exact one-tailed P = 0.18; 95% CI, -0.72 to 0.12). Two patients in the placebo group had developed both duodenal ulcers and gastric ulcers. No adverse events were observed.\n High dose ranitidine is effective for the prevention of recurrent duodenal ulcer but not for recurrent gastric ulcer in rheumatoid arthritis patients taking NSAIDs.", "To compare the efficacy and tolerability of pantoprazole 20 mg once daily (o.d.) with misoprostol 200 microg twice daily (b.i.d.), administered for 6 months to rheumatic patients who required long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and who were at increased risk of developing gastrointestinal lesions.\n This randomized, double-blind, multicenter, parallel group comparison study was performed with rheumatic patients (n = 515) who were likely to take NSAIDs continuously for at least 6 months. Patients were 55 years or older, at risk to develop gastrointestinal lesions, had less than five erosions/petechiae in the stomach and duodenum, no ulcers, no reflux esophagitis (endoscopy-proven), and gastrointestinal symptoms of at most moderate intensity. A minimum daily dose was defined for NSAIDs (COX-2 inhibitors were not available at the time). Patients were randomized to take either pantoprazole 20 mg o.d. (n = 257) or misoprostol 200 microg b.i.d. (n = 258) for 6 months while continuing NSAID therapy. Endoscopy was performed at baseline, 3, and 6 months.\n Pantoprazole was superior to misoprostol (p < 0.001) with regard to 'therapeutic failure' (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, reflux esophagitis, severe gastrointestinal symptoms, and/or 'likely' or 'definitely' related adverse event leading to study termination). Estimated remission rates at 3 and 6 months (Kaplan-Meier life-table analysis) were, respectively, 93 and 89% (pantoprazole) and 79 and 70% (misoprostol). Pantoprazole was superior to misoprostol (p = 0.005) with regard to 'endoscopic failure' (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, or reflux esophagitis) after 6 months. Estimated remission rates at 3 and 6 months were, respectively, 98 and 95% (pantoprazole) and 95 and 86% (misoprostol). Patients discontinuing the study early due to adverse events 'likely' or 'definitely' related to the study drug accounted for 13/257 (5%) in the pantoprazole and 33/258 (13%) in the misoprostol treatment groups.\n Pantoprazole 20 mg o.d. is superior to misoprostol 200 microg b.i.d. in the prevention of NSAID-induced gastrointestinal lesions and symptoms in patients on continuous long-term treatment with NSAIDs due to rheumatic diseases and at risk to develop such lesions or symptoms.\n Copyright 2003 S. Karger AG, Basel", "To evaluate the efficacy of pantoprazole in preventing gastrointestinal lesions in patients with rheumatic diseases receiving continuous, long-term treatment with non-steroidal anti-inflammatory drugs.\n This was a prospective, randomised, double-blind, unbalanced, placebo-controlled, parallel group study. Outpatients (n= 104, age range 22-80 years, mean age 59.5) with rheumatoid arthritis or osteoarthritis, requiring chronic intake of NSAIDs (at least 8 weeks prior to the start of the study), were randomised and enrolled to receive either 40 mg pantoprazole (n=70) or placebo (n=34) once daily, for 12 weeks. Patients had endoscopically confirmed gastric and duodenal lesions grade 0, 1 or 2 (Lanza classification grade 0: normal to hyperaemic mucosa; grade 1: 1 to 3 erosions, submucosal haemorrhage or petechiae, grade 2: 4 to 10 erosions, submucosal haemorrhages or petechiae). Clinical and endoscopic evaluations were performed at baseline, after 4, and 12 weeks. The primary end-point of the study was the incidence of gastric or duodenal ulcers after 4 and 12 weeks of treatment.\n Patients (n=95) were evaluated: 65 in the pantoprazole group and 30 in the placebo group. When considering all patients (those with Lanza score grade 0, 1, 2 at baseline), the overall proportion of patients in remission was 82% and 77% after 4 weeks, and 72% and 59% after 12 weeks in pantoprazole and placebo groups, respectively (cumulative survival analysis according to Kaplan-Meier). The difference between the treatment groups was even more marked when only those patients with normal mucosa at baseline (grade 0) were considered. After 12 weeks, the proportion of patients in remission was 82% (95% confidence limits 70% - 94% in the pantoprazole and 55% (95% confidence limits 33% - 77%) in the placebo treatment group, p=O.036. Adverse events were reported in 4% and 6% of patients in pantoprazole and placebo treatment groups, respectively\n Pantoprazole 40 mg once daily was well tolerated and is more effective than placebo in the prevention of peptic ulcers in patients with rheumatic diseases who require continuous, long-term, treatment with NSAIDs.", "The efficacy of ranitidine in the treatment of NSAID-related dyspeptic symptoms with and without peptic ulcer disease (PUD) was investigated in 124 patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The patients, who continued the use of NSAIDs were investigated by gastroduodenoscopy. Patients with PUD received open label ranitidine 150 mg b.i.d. and the patients without PUD were randomly allocated to receive ranitidine 150 mg b.i.d. or placebo for 4 weeks. PUD was found in 36 (26%) consecutive patients who presented with dyspeptic symptoms. Of these patients dyspeptic symptoms had disappeared in 8 (26%) of 31 evaluable patients and PUD was healed in 18 (56%) patients after 4 weeks of treatment. After 8 weeks of treatment PUD was healed in 27 (87%) patients. Of the remaining patients without PUD dyspeptic symptoms had disappeared in 24 (26%) of the ranitidine-treated patients which was significantly better (p < 0.02) than the 5 (6%) placebo-treated patients. The minor mucosal lesions found in this patient group improved to a similar extent in the ranitidine and placebo-treated patients although 1 placebo-treated patient deteriorated and 2 placebo-treated patients developed PUD during the 4 weeks of study. The results of this study show that oral ranitidine 150 mg b.i.d. is effective in the treatment of both dyspeptic symptoms and mucosal lesions in RA and OA patient who continue the use of NSAIDs.", "Prophylactic misoprostol or non-steroidal anti-inflammatory drugs (NSAIDs) with low gastric toxicity (nabumetone) has been shown to reduce mucosal injury.\n To compare nabumetone vs. co-therapy of naproxen with low-dose misoprostol for secondary prevention of upper gastrointestinal bleeding in NSAID users.\n NSAID users presenting with upper gastrointestinal bleeding were enrolled if they required long-term NSAIDs. After ulcer healing, they were randomized to receive: naproxen (500-1000 mg/day) and misoprostol (200 microg b.d.), or nabumetone (1000-1500 mg/day) and placebo misoprostol for 24 weeks. The primary end-point was recurrent upper gastrointestinal bleeding. The secondary end-point was the proportion of patients suffering from major gastrointestinal events including ulcer bleeding, symptomatic ulcers and severe dyspepsia.\n A total of 90 patients were included in the intention-to-treat analysis (misoprostol/naproxen 45, nabumetone 45). Recurrent bleeding occurred in 10 patients (22.2%) receiving misoprostol/naproxen compared with three (6.7%) receiving nabumetone (relative risk 3.33, 95% CI: 0.98-11.32, P=0.069). The proportion of patients suffering from major gastrointestinal events at 24 weeks was 31.1% in the misoprostol/naproxen group and 28.9% in the nabumetone group.\n Misoprostol/naproxen is not superior to nabumetone for secondary prevention of upper gastrointestinal bleeding. Neither low-dose misoprostol nor nabumetone is adequate for high-risk NSAID users.", "A double-blind, placebo-controlled study was carried out to see whether the synthetic E prostaglandin, misoprostol, would prevent gastric ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). 420 patients with osteoarthritis and NSAID-associated abdominal pain were studied; they were receiving ibuprofen, piroxicam, or naproxen. Endoscopy was done at entry and after 1, 2, and 3 months of continuous treatment with 100 micrograms or 200 micrograms misoprostol or placebo, given four times daily with meals and at bedtime, concurrently with the NSAID. Abdominal pain was rated independently by patients and physicians. A treatment failure was defined as development of a gastric ulcer. Gastric ulcers (0.3 cm in diameter or greater) occurred less frequently (p less than 0.001) in both misoprostol treatment groups (5.6% 100 micrograms and 1.4% 200 micrograms) than in the placebo group (21.7%). The significant difference in ulcer formation between the placebo and the misoprostol treatment groups remained when comparisons were restricted to ulcers greater than 0.5 cm in diameter (12.3% placebo, 4.2% 100 micrograms misoprostol, and 0.7% 200 micrograms misoprostol). Mild to moderate, self-limiting diarrhoea was the most frequently reported adverse effect attributed to misoprostol. These results provide the first clear indication that NSAID-induced ulcers are preventable.", "Two hundred and sixty-nine patients with various rheumatic disorders who had been treated with non-steroidal anti-inflammatory drugs (NSAID) for at least 3 weeks were enrolled in this randomized double-blind multicentre trial. Entry criteria were the presence of an ulcer in the gastric and/or duodenal mucosa (> 3 mm and < 20 mm in diameter) and dyspeptic symptoms. The patients were treated with 150 mg nizatidine nocte (n = 86), 2 x 150 mg/d (n = 93) and 2 x 300 mg/d (n = 90) nizatidine. All patients continued to take their original NSAID medication. The three nizatidine groups were well matched with respect to important patient characteristics. After 8 weeks of treatment more than 90% of gastric and duodenal ulcers (DU) had healed under all three nizatidine dosages. There was a tendency to higher healing rates in the case of gastric ulcers after 4 weeks following the higher dose of nizatidine. Erosion, in the stomach and duodenum as well as oesophagitis, improved to a similar degree with all nizatidine doses. There were similar improvements in clinical symptoms such as epigastric pain, heartburn etc. Consumption of additional antacids were similar in all three groups. In the subsequent prevention trial, 237/221 patients were followed for 3/6 months. In addition to their continued antirheumatic medication 116/107 received nizatidine 150 mg nocte and 121/114 patients 2 x 150 mg nizatidine daily. The cumulative relapse rates within 6 months averaged 5.5% in the low and 1.8% in the high dose group (NS). The safety of nizatidine was assessed as good in both the therapeutic and the preventive trial.(ABSTRACT TRUNCATED AT 250 WORDS)", "Suppressing acid secretion is thought o reduce the risk of ulcers associated with regular use of nonsteroidal antiinflammatory drugs (NSAIDs), but the best means of accomplishing this is uncertain.\n We studied 541 patients who required continuous treatment with NSAIDs and who had ulcers or more than 10 erosions in either the stomach or duodenum. Patients were randomly assigned to double-blind treatment with omeprazole, 20 mg or 40 mg orally per day, or ranitidine, 150 mg orally twice a day, for four or eight weeks, depending on when treatment was successful (defined as the resolution of ulcer and the presence of fewer than five erosions in the stomach, and fewer than five erosions in the duodenum, and not more than mild dyspepsia). We randomly assigned 432 patients in whom treatment was successful to maintenance treatment with either 20 mg of omeprazole per day or 150 mg of ranitidine twice a day for six months.\n At eight weeks, treatment was successful in 80 percent (140 of 174) of the patients in the group given 20 mg of omeprazole per day, 79 percent (148 of 187) of those given 40 mg of omeprazole per day, and 63 percent (110 of 174) of those given ranitidine (P<0.001 for the comparison with 20 mg of omeprazole and P=0.001 for the comparison with 40 mg of omeprazole). The rates of healing of all types of lesions were higher with omeprazole than with ranitidine. During maintenance therapy, the estimated proportion of patients in remission at the end of six months was 72 percent in the omeprazole group and 59 percent in the ranitidine group. The rates of adverse events were similar between groups during both phases. Both medications were well tolerated.\n In patients with regular use of NSAIDs, omeprazole healed and prevented ulcers more effectively than did ranitidine.", "Acid suppression with famotidine, a histamine H2-receptor antagonist, provides protection against gastric injury in normal subjects receiving short courses of aspirin or naproxen. The efficacy of famotidine in preventing peptic ulcers in patients receiving long-term therapy with nonsteroidal antiinflammatory drugs (NSAIDs) is not known.\n We studied the efficacy of two doses of famotidine (20 mg and 40 mg, each given orally twice daily), as compared with placebo, in preventing peptic ulcers in 285 patients without peptic ulcers who were receiving long-term NSAID therapy for rheumatoid arthritis (82 percent) or osteoarthritis (18 percent). The patients were evaluated clinically and by endoscopy at base line and after 4, 12, and 24 weeks of treatment. The evaluators were unaware of the treatment assignment. The primary end point was the cumulative incidence of gastric or duodenal ulceration at 24 weeks.\n The cumulative incidence of gastric ulcers was 20 percent in the placebo group, 13 percent in the group of patients receiving 20 mg of famotidine twice daily (P = 0.24 for the comparison with placebo), and 8 percent in the group receiving 40 mg of famotidine twice daily (P = 0.03 for the comparison with placebo). The proportion of patients in whom duodenal ulcers developed was significantly lower with both doses of famotidine than with placebo (13 percent in the placebo group, 4 percent in the low-dose famotidine group [P = 0.04], and 2 percent in the high-dose famotidine group [P = 0.01]). Both doses of famotidine were well tolerated.\n Treatment with high-dose famotidine significantly reduces the cumulative incidence of both gastric and duodenal ulcers in patients with arthritis receiving long-term NSAID therapy.", "To assess the efficacy of cimetidine in treating and preventing gastric mucosal lesions associated with nonsteroidal anti-inflammatory drug (NSAID) therapy (NSAID gastropathy), we endoscopically studied 104 patients taking NSAIDs for a variety of rheumatic diseases. Fifty-six percent (22/43) of patients randomized to cimetidine 300 mg four times a day and 52% (22/42) of those randomized to placebo showed progression of endoscopic lesions during the eight-week short-term phase. Thirty-nine patients whose endoscopic lesions improved were then randomized to a ten-month maintenance regimen of either cimetidine 400 mg at bedtime or placebo. Fifty percent (7/14) of placebo-treated and 42% (5/12) of cimetidine-treated patients showed progression of lesions during the maintenance phase. The failure of cimetidine to offer any significant benefit under these protocol conditions reflects the fundamental difference in pathophysiologic features between classic acid-mediated ulcer disease and NSAID gastropathy.", "To study whether prophylaxis with lansoprazole could prevent relapse of ulcers after eradication of Helicobacter pylori in patients with NSAID-related peptic ulcers.\n Patients who presented with peptic ulcers and were found to be infected with H. pylori while receiving NSAIDs were recruited into the study. They received, twice daily, lansoprazole 30 mg, amoxicillin 1 g and clarithromycin 500 mg for 1 week, followed by lansoprazole 30 mg daily for 4 weeks. Patients with healed ulcers and H. pylori eradicated were given naproxen 750 mg daily, and randomly assigned to receive lansoprazole 30 mg daily or no treatment for 8 weeks. The primary endpoint was the cumulative recurrence of symptomatic and complicated ulcers.\n At the end of the 8-week treatment period, significantly fewer patients (1/22, 4.5%, 95% confidence interval [CI] 0-23) in the lansoprazole group compared with the group that received H. pylori eradication alone (9/21, 42.9%, 95% CI 22-66) developed recurrence of symptomatic and complicated ulcers (log rank test P=0.0025).\n Lansoprazole significantly reduced the cumulative relapse of symptomatic and complicated ulcers in patients requiring NSAIDs after eradication of H. pylori.", "We performed a 12-month, double-blind, randomised, placebo-controlled study to determine the long term effect of misoprostol (600-800 micrograms/d) in the prevention of gastric ulcers and gastroduodenal erosions in 83 arthritis patients on chronic NSAID therapy. Patients underwent endoscopy at 0, 3, 6 and 12 months. At the initial endoscopy, 12 patients had an ulcer (11 gastric), which was healed prior to randomization. Seventy eligible patients reached the 3 month endoscopy. Four (12.5%) of the 32 patients given misoprostol developed a gastric ulcer compared with 11 (28.9%) of the 38 on placebo (p < 0.05, life-table analysis). Six of the 11 patients with an initial gastric ulcer developed a further gastric ulcer, compared to 9 of 58 patients without an initial ulcer (p < 0.05). We conclude that misoprostol decreases the cumulative development of NSAID-induced gastric ulcers. Patients with a previous NSAID-ulcer have a higher risk of further ulceration." ]

[ "9093725", "7819058", "7683942" ]

[ "Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer.", "A randomised trial of octreotide vs best supportive care only in advanced gastrointestinal cancer patients refractory to chemotherapy.", "Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer." ]

[ "The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients.\n Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument.\n More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physician's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03).\n The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited.", "Octreotide, a somatostatin analogue, has been shown to inhibit the growth of gastrointestinal cancers in vitro and in vivo. To assess the anti-tumour effect of octreotide, we performed a randomised trial comparing octreotide with best supportive care in advanced gastrointestinal cancer patients refractory to chemotherapy. A total of 107 patients with advanced gastrointestinal cancer refractory to chemotherapy were randomised to receive octreotide at the dose of 200 micrograms three times a day for 5 days a week, or the best supportive care only. The primary outcome variable was the survival duration. Response rate was an outcome variable of secondary importance. Fifty-five patients (15 stomach, 16 pancreas, 24 colon-rectum) received octreotide, while 52 (14 stomach, 16 pancreas, 22 colon-rectum) received the best supportive care. Patients treated with octreotide had a significant advantage in duration of survival with a median survival time of 20 weeks vs 11 in the control group (P < 0.0001). This advantage was present also considering the survival data for each tumour group. Twenty-five patients (45%) given octreotide showed stable disease vs only eight (15%) in the control group (P < 0.001). In conclusion, octreotide therapy seems to confer a survival benefit in advanced gastrointestinal cancer patients refractory to chemotherapy. Additional studies will be needed to confirm these results and to clarify other questions about dose and schedule of octreotide.", "To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care.\n Randomised study.\n Gastrointestinal oncology departments.\n 40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic.\n Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle.\n Length of survival and quality of life score with an optimised functional living index-cancer scale.\n Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm.\n In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment." ]

[ "15557131", "17710485", "8339624", "12728156", "4404939" ]

[ "Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.", "Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization.", "Hydrocortisone and tumor necrosis factor in severe community-acquired pneumonia. A randomized controlled study.", "Dexamethasone for treatment of patients mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus.", "Ampicillin dosage and use of prednisolone in treatment of pneumonia: co-operative controlled trial." ]

[ "We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications. In a multicenter trial, patients admitted to the Intensive Care Unit (ICU) with severe community-acquired pneumonia received protocol-guided antibiotic treatment and were randomly assigned to hydrocortisone infusion or placebo. Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days. Primary end-points of the study were improvement in Pa(O(2)):FI(O(2)) (Pa(O(2)):FI(O(2)) > 300 or >/= 100 increase from study entry) and multiple organ dysfunction syndrome (MODS) score by Study Day 8 and reduction in delayed septic shock. Forty-six patients entered the study. At study entry, the hydrocortisone group had lower Pa(O(2)):FI(O(2)), and higher chest radiograph score and C-reactive protein level. By Study Day 8, treated patients had, compared with control subjects, a significant improvement in Pa(O(2)):FI(O(2)) (p = 0.002) and chest radiograph score (p < 0.0001), and a significant reduction in C-reactive protein levels (p = 0.01), MODS score (p = 0.003), and delayed septic shock (p = 0.001). Hydrocortisone treatment was associated with a significant reduction in length of hospital stay (p = 0.03) and mortality (p = 0.009).", "Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.\n The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.\n An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.\n Thirty-one adult CAP patients who required hospitalization were enrolled.\n Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.\n In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy.", "Community-acquired pneumonia is a major cause of death in third world countries. Antimicrobial therapy may have little impact on the natural history of patients with severe pneumonia. We hypothesized that the intrapulmonary production of tumor necrosis factor-alpha (TNF-alpha) may be responsible for the progressive lung injury and shock commonly seen in patients with severe pneumonia after commencing antibiotic therapy.\n To investigate the effects of a single bolus of hydrocortisone on the clinical course and serum TNF-alpha levels of patients with severe community-acquired pneumonia.\n Randomized placebo-controlled study.\n Multidisciplinary ICU of a tertiary care teaching hospital.\n Patients with three or more British Thoracic Society criteria of severe pneumonia were studied. Patients were randomized to receive either a single dose of hydrocortisone (10 mg/kg) or placebo 30 min prior to commencing antibiotic therapy. Patients were treated with cefotaxime and other antibiotics as clinically indicated. Blood for TNF-alpha was taken at the time of hospital admission and repeated 2, 6, and 12 h after starting antibiotic therapy.\n Thirty patients were studied: 16 received placebo and 14 received hydrocortisone. The patients who received placebo tended to be sicker than the patients who received hydrocortisone. The baseline TNF-alpha value was 989 +/- 374 pg/ml in the placebo group and 827 +/- 394 pg/ml in the hydrocortisone group. In both groups of patients, the TNF-alpha levels did not change significantly with time. There was no correlation between the TNF-alpha levels and the APACHE II score, lung injury score, or outcome. The only variable that predicted outcome was the APACHE II score.\n Bactericidal antibiotics do not increase serum TNF-alpha levels in patients with severe pneumonia. Hydrocortisone given prior to antibiotic treatment had no effect on the serum TNF-alpha levels or the clinical course of patients with severe community-acquired pneumonia.", "A study was undertaken to evaluate the efficacy of dexamethasone in patients mechanically ventilated for lower respiratory infection caused by respiratory syncytial virus (RSV-LRTI).\n In a multicentre randomised controlled trial patients were randomised to receive either intravenous dexamethasone (0.15 mg/kg 6 hourly for 48 hours) or placebo. End points were the duration of mechanical ventilation, length of stay (LOS) in the pediatric intensive care unit (PICU) and in hospital, and the duration of supplemental oxygen administration.\n Thirty seven patients received dexamethasone and 45 received placebo. There was no significant difference in any of the end points between the two groups. In a post hoc analysis patients were stratified into those with mild gas exchange anomalies (PaO(2)/FiO(2) >200 mm Hg and/or mean airway pressure </= 10 cm H(2)O, bronchiolitis group) and those with severe gas exchange anomalies (PaO(2)/FiO(2) </=200 mm Hg and mean airway pressure >10 cm H(2)O, pneumonia group). In the 39 patients with bronchiolitis the duration of mechanical ventilation was 4.3 days shorter in the dexamethasone group than in the placebo group (4.9 v 9.2 days, 95% CI -7.8 to -0.8, p=0.02) and the duration of supplemental oxygen was 3.6 days shorter (7.7 v 11.3 days, 95% CI -8.0 to -0.1, p=0.048). No differences in end points were found in the pneumonia group.\n Dexamethasone had no beneficial effect in patients mechanically ventilated for RSV-LRTI but was found to have a beneficial effect in patients with bronchiolitis.", "A controlled trial was carried out to investigate whether the rate of recovery from pneumonia treated with ampicillin is dose related. Sixty-three patients received 1 g ampicillin daily and 63 received 2 g ampicillin daily for seven or 14 days depending on the rate of response. Twenty patients in each of these groups received, in addition, 20 mg prednisolone daily for seven days. The treatment groups were comparable and the results of treatment were similar in the four groups. The only difference which was of statistical significance was that a larger proportion of patients receiving 1 g ampicillin daily became afebrile within one week. All the ampicillin rashes occurred in the patients receiving 2 g ampicillin daily with and without prednisolone. Ampicillin 1 g daily appears to be adequate dosage in the treatment of pneumonia, and the rate of recovery has not been shown to be accelerated by using 2 g. No deleterious effects were noted with additional prednisolone therapy and this appeared to increase the rate at which the patients became afebrile, although the figures were not statistically significant." ]

[ "8688399", "16489694", "2206076", "8885732", "2657045", "8238121", "1892185", "8885731", "8238158", "7503194", "7005777", "6990761" ]

[ "Double-blind evaluation of ritodrine sustained release for oral maintenance of tocolysis after active preterm labour.", "Ritodrine in oral maintenance of tocolysis after active preterm labor: randomized controlled trial.", "A prospective randomized comparison of oral terbutaline and magnesium oxide for the maintenance of tocolysis.", "The clinical efficacy of oral tocolytic therapy.", "Randomized comparison of oral terbutaline and ritodrine for preventing recurrent preterm labor.", "Randomized trial of oral indomethacin and terbutaline sulfate for the long-term suppression of preterm labor.", "Oral tocolysis with magnesium chloride: a randomized controlled prospective clinical trial.", "Oral terbutaline after parenteral tocolysis: a randomized, double-blind, placebo-controlled trial.", "The efficacy of oral terbutaline after intravenous tocolysis.", "Oral terbutaline in the outpatient management of preterm labor.", "Terbutaline sulfate in the prevention of recurrence of premature labor.", "Oral ritodrine maintenance in the treatment of preterm labor." ]

[ "To evaluate the effect of ritodrine sustained release capsules for maintaining uterine quiescence after successful treatment of active preterm labour.\n Multicentre placebo-controlled trial.\n Five teaching hospitals in the Netherlands.\n Women (n = 95) at less than 35 weeks of gestation in whom active preterm labour had been stopped with intravenous ritodrine.\n Women received either two 40 mg ritodrine sustained release capsules (n = 50) or identical placebo capsules (n = 45) three times a day for seven days.\n The proportion of women who received another course of active treatment was significantly smaller with the sustained release than with placebo (1 of 50 versus 11 of 45: P = 0.003) as was the number delivering because of preterm labour during treatment (0 of 50 versus 4 of 45: P = 0.04). There were no other significant differences between the two groups.\n Maintenance treatment with ritodrine sustained release capsules after arrest of preterm labour reduces the risk of recurrences of preterm labour that necessitate treatment or precipitate delivery.", "To assess the efficacy of oral ritodrine in the form of sustained-release capsules for maintenance of uterine quiescence after successful treatment of threatened preterm labor.\n We randomized 120 women with singleton pregnancy who were successfully treated for threatened preterm labor before 34 completed weeks to receive either maintenance tocolysis with two 40 mg ritodrine sustained release capsules three times a day (study group, n=62) or no treatment (control group, n=58) for three days. The primary outcome measure was the recurrent episode of threatened preterm labor within 72 hours, which was defined as regular palpable uterine contractions and change in cervical effacement or cervical dilatation on clinical examination. Secondary outcome measures included the incidence of preterm birth, neonatal adverse outcomes, and maternal side effects.\n There was no difference in the frequency of recurrent episodes of threatened preterm labor requiring another course of intravenous treatment between the study (8/62) and control (6/58) group of women (P=0.879). No differences were found between the study and control groups in any of the predefined secondary outcome measures, ie, delivery before 37 weeks (13/62 vs 7/58, respectively; P=0.288), delivery before 34 weeks (3/62 vs 1/58, respectively; P=0.682) and birth weight (3037-/+573 g vs 3223-/+423 g, respectively, P=0.862). There were more reported maternal side effects in the study group than in control group (47/62 vs 23/58, respectively; P(<0.001).\n Additional maintenance ritodrine therapy was unnecessary in women with singleton pregnancy who had an episode of threatened preterm labor successfully treated with intravenous tocolytic therapy.\n ClinicalTrials.gov Identifier: NCT00290173.", "We compared oral magnesium oxide with oral terbutaline sulfate in a prospective, randomized manner to determine efficacy and side effects. Preterm labor patients whose labor was arrested with parenteral tocolysis were randomized to oral tocolysis with either magnesium oxide, 200 mg every 3 to 4 hours (n = 23), or terbutaline, 2.5 to 5 mg every 3 to 4 hours (n = 27). The number of patients who were delivered of infants before 36 weeks' gestation was similar between groups (18.5% receiving terbutaline versus 17.4% receiving magnesium). At least one side effect occurred in 81.5% of patients in the terbutaline group and 47.8% in the magnesium group (p less than 0.01). Finally, the cost for 1 day of magnesium (20 cents) is approximately one third the cost of terbutaline (56 cents). These data suggest that oral magnesium oxide is as effective as terbutaline for the maintenance of tocolysis, with fewer side effects and at a lower cost.", "Our purpose was to determine whether maintenance oral tocolytic therapy after preterm labor stabilization decreases uterine activity, reduces the rate of recurrent preterm labor and subsequent preterm birth, or improves neonatal outcome.\n Women with documented idiopathic preterm labor stabilized with acute tocolytic therapy were randomized to three groups: placebo, terbutaline 5 mg, or magnesium chloride 128 mg, all given orally every 4 hours. Patients and providers were blinded to group assignment. All subjects were enrolled in a comprehensive system of preterm birth prevention that included preterm labor education, weekly clinic visits, home uterine contraction assessment, daily phone contact, and 24-hour perinatal nurse access.\n Of the 248 patients who were randomized, 39 were delivered before discharge and 4 were lost to follow-up, leaving 205 for final analysis: 68 placebo, 72 terbutaline, and 65 magnesium. The terbutaline group had significantly more side effects than the placebo group did. All groups had otherwise similar perinatal outcomes when confounding variables were controlled for. Overall, the three groups had a preterm birth rate < 37 weeks of 55.6% delivery, < 34 weeks of 15.6%, a 20.4% rate of newborn intensive care unit admission, and a mean neonatal length of stay of 6.3 days.\n Maintenance oral tocolytic therapy did not decrease uterine activity, reduce the rate of recurrent preterm labor or preterm birth, or improve perinatal outcome. Overall improvement in perinatal outcome may be achieved with a comprehensive program of preterm birth prevention without the use of maintenance oral tocolytic therapy.", "We compared oral ritodrine and terbutaline for the prevention of recurrent preterm labor. Women between 20 and 35 weeks' gestation who successfully completed a course of intravenous tocolysis were eligible for inclusion. One hundred two patients were randomized to oral ritodrine (20 mg every four hours) or oral terbutaline (5 mg every four hours). The groups showed no significant differences with respect to recognized risk factors for preterm labor or prognostic factors for the failure of tocolysis. Initial treatment failures occurred more frequently in the ritodrine group (nine vs. two, P = .0527). There were no statistically significant differences in the treatment results or frequency of side effects. We conclude that ritodrine appears to be less effective than terbutaline upon the initiation of oral therapy and that oral ritodrine and terbutaline are equivalent in safety and efficacy when used on a long-term basis for preventing recurrent preterm labor.", "Our purpose was to determine the efficacy and safety of long-term oral tocolysis with indomethacin or terbutaline sulfate.\n Seventy-one patients at 26 to 32 weeks' gestation admitted for preterm labor were prospectively randomized to receive oral indomethacin or terbutaline sulfate after successful intravenous tocolysis. Patients were monitored weekly for cervical change, maternal side effects, amniotic fluid volume, and constriction of the fetal ductus arteriosus. Patients receiving indomethacin were converted to terbutaline at 34 weeks or with the occurrence of fetal ductal constriction or oligohydramnios.\n Of 71 patients randomized six were excluded after randomization. Thirty-three patients were randomized to indomethacin and thirty-two to terbutaline. There were no differences in the percentage of patients achieving 34 weeks of gestation. No differences in neonatal outcome were noted. Nine (27%) fetuses receiving indomethacin had constriction of the fetal ductus arteriosus, and 13 (38%) had oligohydramnios. Most patients on terbutaline reported beta-mimetic side effects (53%), but only one required discontinuation of therapy.\n Both indomethacin and terbutaline sulfate are effective tocolytics, but major fetal side effects are common with long-term indomethacin use.", "A prospective randomized clinical trial was conducted to assess the efficacy and safety of enteric-coated magnesium chloride (SLOW MAG) as an oral tocolytic agent. Seventy-five patients between 24 and 34 weeks' gestation who were treated with intravenous magnesium sulfate for a first episode of preterm labor were enrolled. After a 12-hour contraction-free period on intravenous therapy, patients were randomized by sealed envelope to one of three groups: group 1, SLOW MAG (535 mg every 4 hours); group 2, oral ritodrine (20 mg every 4 hours); or group 3, no therapy (control). Patients receiving oral therapy were treated until delivery or completion of 36 weeks' gestation. No difference was found between groups with respect to time gained with the use of oral therapy or number completing 36 weeks' gestation. Therapy with enteric-coated magnesium chloride was associated with significantly fewer side effects (20%) as compared with ritodrine (48%) (p less than 0.01). Our results suggest that compared with ritodrine, enteric-coated magnesium chloride is as effective in prolonging pregnancy and preventing recurrent preterm labor. However, neither enteric-coated magnesium chloride nor ritodrine appeared to be any more effective in the prevention of preterm delivery than observation alone.", "Our purpose was to determine whether oral terbutaline, used after successful intravenous tocolysis, will prolong pregnancy and prevent recurrent preterm labor.\n After successful intravenous tocolysis, 203 women with preterm labor at 24 weeks' to 34 weeks 6 days' gestation were randomized to terbutaline (5 mg orally, every 4 hours) or placebo until 37 weeks' gestation. Women with recurrent preterm labor were treated with intravenous magnesium sulfate; if tocolysis was successful, they continued with the initial study medication. The primary outcome was the percentage delivered of their infants within 1 week of beginning oral tocolytic therapy. Latency, recurrent preterm labor, and maternal and neonatal outcomes were also assessed.\n Pregnancy outcome data were available in 200 women. There were no differences seen between the two groups in the incidence of delivery at 1 week (18% vs 24%, 95% confidence interval 0.44 to 1.29). In addition, there were no differences regarding median latency, mean gestational age at delivery, or the incidence of recurrent preterm labor (20% vs 16%, 95% confidence interval 0.64 to 2.71). Post hoc evaluation of 96 women enrolled before 32 weeks' gestation suggested pregnancy prolongation with maintenance oral terbutaline (p < 0.01).\n Maintenance oral terbutaline therapy initiated at 24 weeks' to 34 weeks 6 days' gestation after successful parenteral tocolysis is not associated with pregnancy prolongation or a reduction in the incidence of recurrent preterm labor.", "Our purpose was to investigate in a prospective, randomized study the efficacy of oral terbutaline after successful intravenous tocolysis in reducing preterm birth.\n Patients between 28 and 35 weeks' gestation with uterine contractions and change in cervical examination were treated with intravenous magnesium sulfate for 12 to 24 hours. After successful tocolysis patients were approached for study participation and randomized to receive either oral terbutaline or no therapy. The dose of terbutaline was individualized to achieve a maternal pulse > 100 beats/min, and terbutaline was continued until 36 completed weeks of gestation. Recurrent preterm labor (contractions with change in cervical examination) for either group was treated with intravenous magnesium sulfate, and subsequent treatment was based on the previous randomization.\n Fifty-five patients were enrolled (28 terbutaline, 27 no oral tocolytic). No difference was found between groups with respect to time gained (4.0 +/- 2.7 vs 4.6 +/- 3.1 weeks, p = 0.412), gestational age at delivery (35.6 +/- 2.7 vs 36.1 +/- 2.4 weeks, p = 0.562), > or = 37 weeks at delivery (nine vs 13, p = 0.291), recurrent preterm labor (10 vs four, p = 0.104), recurrent uterine contractions alone (five vs eight, p = 0.527), birth weight (2616 +/- 633 gm vs 2645 +/- 599 gm, p = 0.785), special care nursery admissions (eight vs six, p = 0.759), or neonatal respiratory distress syndrome (three vs two, p = 0.965).\n The use of oral terbutaline after successful parenteral tocolysis failed to reduce the rate of preterm birth.", "Our purpose was to prove our hypothesis that once preterm uterine contractions and/or labor is controlled with intravenous tocolysis, oral terbutaline, as a maintenance drug, does not prolong pregnancy.\n Before discharge, 184 patients between 24 and 35 completed weeks' gestation were prospectively randomized to continued bed rest either with or without oral terbutaline. Assignment was made with stratification into four groups: group 1, those patients with a Bishop score > or = 5 with oral terbutaline (n = 50); group 2, those with a Bishop score > or = 5 without oral terbutaline (n = 53); group 3, those with a Bishop score < 5 with oral terbutaline (n = 41); group 4, those with a Bishop score < 5 without oral terbutaline (n = 40). Oral terbutaline was discontinued at 37 completed weeks.\n No statistically significant differences were found in the number of readmissions, the number of unscheduled hospital visits, and the neonatal outcomes among the four groups. The gestational age at delivery and percent of deliveries at > or = 37 weeks were not significantly different when group 1 was compared with group 2 and group 3 was compared with group 4.\n Oral terbutaline maintenance does not improve pregnancy outcome in patients who have had initial successful intravenous tocolysis.", "Forty-six patients in premature labor were initially successfully treated with ethanol infusion. Twenty-three of these patients were then given prolonged oral terbutaline sulfate therapy until 38 weeks' gestation, and the remaining 23 patients were given placebo. The treated group gained significantly more time in gestation than the placebo group (P < .05), although the placebo group started with a higher Bishop score. In addition, idiopathic respiratory distress syndrome was seen significantly less often in the treated group. There was no perinatal mortality in either group.", "Seventy patients with preterm labor and intact membranes were initially treated with ritodrine hydrochloride to delay preterm delivery. Tocolysis beyond 24 hours was achieved in 59 patients. Fifty-five of the 59 patients were then placed on either oral ritodrine or placebo as maintenance therapy in a randomized double-blind manner. If preterm labor recurred, the sequence of intramuscular and then oral treatment was repeated. The number of days gained after initiation of intramuscular treatment was similar in both groups (oral ritodrine = 34 days, oral placebo = 36 days). In those 55 patients receiving oral treatment, there was a smaller number of relapses requiring repeat intramuscular treatment in the oral ritodrine group (1.11 in the ritodrine patient vs. 2.71 in the placebo patient, p less than 0.05), and the mean interval between beginning oral treatment and the first relapse/delivery was 5.8 days in the oral placebo group and 25.9 in those receiving oral ritodrine (p less than 0.05). Cardiovascular side effects, notably maternal tachycardia and palpitations were frequent but well tolerated. The results suggest that oral ritodrine maintenance will decrease the incidence of recurrent preterm labor in patients who have had initial successful tocolysis." ]

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[ "A randomized controlled study of reviewer bias against an unconventional therapy.", "Effect of open peer review on quality of reviews and on reviewers' recommendations: a randomised trial.", "Effect of blinding and unmasking on the quality of peer review: a randomized trial.", "Does exchanging comments of Indian and non-Indian reviewers improve the quality of manuscript reviews?", "An exploratory study of statistical assessment of papers published in the British Medical Journal.", "Calling Medical Care reviewers first. A randomized trial.", "Reviewer bias against the unconventional? A randomized double-blind study of peer review.", "The effects of blinding on acceptance of research papers by peer review.", "Effect of written feedback by editors on quality of reviews: two randomized trials.", "The use of dedicated methodology and statistical reviewers for peer review: a content analysis of comments to authors made by methodology and regular reviewers.", "Identifying manuscript reviewers: randomized comparison of asking first or just sending.", "A comparison of authors publishing in two groups of U.S. medical journals.", "Does masking author identity improve peer review quality? A randomized controlled trial. PEER Investigators.", "Comparison of review articles published in peer-reviewed and throwaway journals.", "Readers' evaluation of effect of peer review and editing on quality of articles in the Nederlands Tijdschrift voor Geneeskunde.", "Effects of training on quality of peer review: randomised controlled trial.", "Evaluating the BMJ guidelines for economic submissions: prospective audit of economic submissions to BMJ and The Lancet.", "The Medical Journal of Australia Internet peer-review study.", "Effect of structured workshop training on subsequent performance of journal peer reviewers.", "Manuscript quality before and after peer review and editing at Annals of Internal Medicine.", "An intervention to improve the reliability of manuscript reviews for the Journal of the American Academy of Child and Adolescent Psychiatry.", "The effects of blinding on the quality of peer review. A randomized trial.", "Effect on the quality of peer review of blinding reviewers and asking them to sign their reports: a randomized controlled trial.", "Effect of attendance at a training session on peer reviewer quality and performance.", "[Effect of statistical review on manuscript quality in Medicina Clínica (Barcelona): a randomized study].", "Open peer review: a randomised controlled trial." ]

[ "A study was designed to test the hypothesis that experts who review papers for publication are prejudiced against an unconventional form of therapy. Two versions were produced (A and B) of a 'short report' that related to treatments of obesity, identical except for the nature of the intervention. Version A related to an orthodox treatment, version B to an unconventional treatment. 398 reviewers were randomized to receive one or the other version for peer review. The primary outcomes were the reviewers' rating of 'importance' on a scale of 1-5 and their verdict regarding rejection or acceptance of the paper. Reviewers were unaware that they were taking part in a study. The overall response rate was 41.7%, and 141 assessment forms were suitable for statistical evaluation. After dichotomization of the rating scale, a significant difference in favour of the orthodox version with an odds ratio of 3.01 (95% confidence interval, 1.03 to 8.25), was found. This observation mirrored that of the visual analogue scale for which the respective medians and interquartile ranges were 67% (51% to 78.5%) for version A and 57% (29.7% to 72.6%) for version B. Reviewers showed a wide range of responses to both versions of the paper, with a significant bias in favour of the orthodox version. Authors of technically good unconventional papers may therefore be at a disadvantage in the peer review process. Yet the effect is probably too small to preclude publication of their work in peer-reviewed orthodox journals.", "To examine the effect on peer review of asking reviewers to have their identity revealed to the authors of the paper.\n Randomised trial. Consecutive eligible papers were sent to two reviewers who were randomised to have their identity revealed to the authors or to remain anonymous. Editors and authors were blind to the intervention.\n The quality of the reviews was independently rated by two editors and the corresponding author using a validated instrument. Additional outcomes were the time taken to complete the review and the recommendation regarding publication. A questionnaire survey was undertaken of the authors of a cohort of manuscripts submitted for publication to find out their views on open peer review.\n Two editors' assessments were obtained for 113 out of 125 manuscripts, and the corresponding author's assessment was obtained for 105. Reviewers randomised to be asked to be identified were 12% (95% confidence interval 0.2% to 24%) more likely to decline to review than reviewers randomised to remain anonymous (35% v 23%). There was no significant difference in quality (scored on a scale of 1 to 5) between anonymous reviewers (3.06 (SD 0.72)) and identified reviewers (3.09 (0.68)) (P=0.68, 95% confidence interval for difference - 0.19 to 0.12), and no significant difference in the recommendation regarding publication or time taken to review the paper. The editors' quality score for reviews (3.05 (SD 0.70)) was significantly higher than that of authors (2.90 (0.87)) (P<0.005, 95%confidence interval for difference - 0.26 to - 0.03). Most authors were in favour of open peer review.\n Asking reviewers to consent to being identified to the author had no important effect on the quality of the review, the recommendation regarding publication, or the time taken to review, but it significantly increased the likelihood of reviewers declining to review.", "Little research has been conducted into the quality of peer review and, in particular, the effects of blinding peer reviewers to authors' identities or masking peer reviewers' identities.\n To determine whether concealing authors' identities from reviewers (blinding) and/or revealing the reviewer's identity to a coreviewer (unmasking) affects the quality of reviews, the time taken to carry out reviews, and the recommendation regarding publication.\n Randomized trial of 527 consecutive manuscripts submitted to BMJ, which were randomized and each sent to 2 peer reviewers.\n Manuscripts were randomized as to whether the reviewers were unmasked, masked, or uninformed that a study was taking place. Two reviewers for each manuscript were randomized to receive either a blinded or an unblinded version.\n Mean total quality score, time taken to carry out the review, and recommendation regarding publication.\n Of the 527 manuscripts entered into the study, 467 (89%) were successfully randomized and followed up. The mean total quality score was 2.87. There was little or no difference in review quality between the masked and unmasked groups (scores of 2.82 and 2.96, respectively) and between the blinded and unblinded groups (scores of 2.87 and 2.90, respectively). There was no apparent Hawthorne effect. There was also no significant difference between groups in the recommendations regarding publication or time taken to review.\n Blinding and unmasking made no editorially significant difference to review quality, reviewers' recommendations, or time taken to review. Other considerations should guide decisions as to the form of peer review adopted by a journal, and improvements in the quality of peer review should be sought via other means.", "The quality of peer reviewing in developing countries is thought to be poor. To examine whether this was so, we compared the performance of Indian and non-Indian reviewers who were sent original and review articles submitted to The National Medical Journal of India. We also tested whether informing reviewers that their comments would be exchanged improved the quality of their reviews.\n In a prospective, randomized, blinded study, we sent 100 manuscripts to pairs of peer reviewers (Indian and non-Indian) of which 78 pairs of completed replies were available for analysis. Thirty-eight pairs of reviews were exchanged and 40 were not. The quality of the reviews was assessed by two editors who were unaware of the reviewers' nationality and whether they had been told that their reviews would be exchanged. The quality of the reviews was scored out of 100 (based on a predesigned evaluation proforma). We also measured the time taken to return a manuscript.\n Overall, non-Indian reviewers scored higher than Indians (mean scores non-Indians first, 56.7 v. 48.6, p < 0.001), especially those in the non-exchanged group (58.4 v. 47.3, p < 0.001) but not the exchanged group (54.8 v. 50.0, p < 0.06). Being informed that reviews would be exchanged did not affect the quality of reviews by non-Indians (54.8 exchanged v. 58.4 non-exchanged) or of reviews by Indians (50.0 exchanged v. 47.3 non-exchanged). The editors' assessment of the reviewers matched well (r = 0.59, p < 0.001). Non-Indians took the same amount of time as Indians to return their reviews, although the postage time was at least eight days longer.\n We found that non-Indian peer reviewers were better than Indians and informing them that their views would be exchanged did not seem to affect the quality of their reviews. We suggest that Indian editors should also use non-Indian reviewers and start training programmes to improve the quality of peer reviews in India.", "Statistical assessment of papers submitted to the British Medical Journal has increased to some 300 papers annually. The assessment produces a recommendation to the editor on each paper from a statistical viewpoint together with a completed checklist that indicates the quality of certain important features. This exploratory study was aimed at monitoring the process. It reports a comparison of checklist answers on 45 papers as originally submitted with those on the papers as subsequently published. Of the 45 papers, only 5 (11%) were considered statistically acceptable at submission, but this increased to 38 (84%) after publication. Revisions had not been made adequately in 4 of the 7 unsatisfactory published papers, and the 3 others were thought to be of dubious validity. A major omission from at least 28 papers was information on sample size calculations. It is concluded that statistical assessment is beneficial but that further efforts by authors and assessors could make it even more effective.", "nan", "To test the hypothesis that there is a reviewer bias against publication of a test of an unconventional drug.\n Randomized, controlled, double-blind study of peer review.\n Convenience sample of 291 medical doctors from a wide variety of specialties drawn from a list of conference participants.\n Reviewers were randomly assigned to receive one of two versions of a manuscript. Version M related to an in-vitro experiment on a mainstream drug (Metoprolol). The otherwise identical version V used a highly unconventional drug (beef spleen cell extract) for the same experiment. Reviewers were asked to complete a standardised evaluation sheet including visual analogue scales (VASs) on a set of predefined quality criteria. All participants were debriefed after completion of the study.\n The response rate was 61%. There were no significant differences in VAS ratings between the two versions of the manuscript. Ratings covered the entire range of the VASs.\n In the present setting, there was no evidence for a reviewer-bias against testing an unconventional drug. The low inter-rater reliability, however, suggested inadequate validity of peer review.", "To study whether reviewers aware of author identity are biased in favor of authors with more previous publications.\n Randomized controlled trial.\n Editorial office of the Journal of Developmental and Behavioral Pediatrics.\n Two \"blinded\" and two \"nonblinded\" reviewers assigned to 57 consecutive manuscripts submitted between September 1991 and March 1992.\n Spearman rank correlation coefficients were used to compare the sum of rating scores of 1 to 5 (1, accept; 5, reject) given by the two blinded reviewers, the two nonblinded reviewers, and the editors to the number of articles published previously by the first and senior authors (as determined from requested curricula vitae). Blinded reviewers were sent a questionnaire asking whether they could determine the identity of the authors, how they knew, and whether they thought binding changed the quality or difficulty of their review.\n The Wilcoxon Sign Rank Test disclosed no differences between blinded and nonblinded scores. The number of previous articles by the senior author was significantly correlated (P < .01) with blinded scores (r = -.45) and editors' decisions (r = -.45), but not with nonblinded scores; the number of articles by the first author was correlated (P < .05) with editors' decisions (r = -.35) but not with blinded or nonblinded scores. Fifty (46%) of 108 blinded reviewers correctly guessed the identity of the authors, mostly from self-references and knowledge of the work; 86% believed blinding did not change the quality of their review, and 73% believed it did not change the difficulty of performing a review.\n Blinded reviewers and editors in this study, but not nonblinded reviewers, gave better scores to authors with more previous articles. These results suggest that blinded reviewers may provide more unbiased reviews and that nonblinded reviewers may be affected by various types of bias.", "Better peer review is needed, but proven methods to improve quality are unknown. Our objective was to determine whether written feedback to reviewers improves subsequent reviews.\n Eligible reviewers were randomized to intervention or control (receiving other reviewers' unscored reviews and the editor's decision letter). Study 1 (September 1998-September 2000) included reviewers with a median quality score of 3 or lower; study 2 (April 2000-January 2002), reviewers with median score of 4 or lower. Study 1 was designed with a power of 0.80 to detect a difference in score of 1; study 2, with a power of 0.80 to detect a difference of 0.5. All reviewers were at a peer-reviewed journal (Annals of Emergency Medicine). The main outcome measure was the editor's routine quality rating (1-5) of all reviews (blinded to study enrollment).\n For study 1, 51 reviewers were eligible and randomized and 35 had sufficient data (182 reviews) for analysis. The mean individual reviewer rating change was 0.16 (95% confidence interval [CI], -0.26 to 0.58) for control and -0.13 (-0.49 to 0.23) for intervention. For study 2, 127 reviewers were eligible and randomized, and 95 had sufficient data (324 reviews). Controls had a mean individual rating change of 0.12 (95% CI, -0.20 to 0.26) and intervention reviewers, 0.06 (-0.19 to 0.31).\n In study 1, minimal feedback from editors on review quality had no effect on subsequent performance of poor-quality reviewers, and the trend was toward a negative effect. In study 2, feedback to average reviewers was more extensive and supportive but produced no improvement in reviewer performance. Simple written feedback to reviewers seems to be an ineffective educational tool.", "In 1997, Annals of Emergency Medicine initiated a protocol by which every original research article, in addition to each regular review, was concurrently evaluated by 1 of 2 methodology and statistical reviewers. We characterized and contrasted comments made by the methodology and regular peer reviewers.\n After pilot testing, interrater reliability assessment, and revision, we finalized a 99-item taxonomy of reviewer comments organized in 8 categories. Two authors, uninvolved in the writing of reviews, classified each comment from a random sample of methodology reviews from 1999. For 30 of these reviews (15 for each methodology reviewer), the 2 authors also scored all (range 2 to 5) regular reviews.\n Sixty-five reviews by methodologist A, 60 by methodologist B, and 68 by regular reviewers were analyzed. Comments by methodologist A most frequently concerned the presentation of results (33% of all comments) and methods (17%). Methodologist B commented most frequently on presentation of results (28%) and statistical methods (16%). Regular reviewers most frequently made non-methodology/statistical comments (45%) and comments on presentation of results (18%). Of note, comments made by methodology and regular reviewers about methods issues were often contradictory.\n The distributions of comments made by the 2 methodology and statistical reviewers were similar, although reviewer A emphasized presentation and reviewer B stressed statistical issues. The regular reviewers (most of whom were unaware that a dedicated methodology and statistical reviewer would be reviewing the article) paid much less attention to methodology issues. The 2 dedicated methodology and statistical reviewers created reviews that were similarly focused and emphasized methodology issues that were distinct from the issues raised by regular reviewers.", "Some journals routinely query potential referees before sending manuscripts (\"askfirst\"), whereas others just send manuscripts and allow referees to opt out (\"justsend\"). It is not known which protocol results in more completed reviews or shorter review time.\n Trial to assess proportion of referee turndowns and length of review process, conducted at editorial office of Obstetrics & Gynecology and involving 283 consecutive qualifying manuscripts. For each, a referee was randomly assigned to askfirst (manuscript sent only after affirmative response within 3 days) and another to justsend (manuscript sent with request to review; could opt out).\n Only 64% of askfirst referees assented initially (15% declined [vs 8% for justsend, P =.008] and 21% failed to respond within 3 working days, necessitating a replacement). But once manuscript was mailed, mean time to file a review was significantly shorter for askfirst (21.0 vs 25.0 days, P<.001); thus, overall time to receipt of review did not differ significantly (24.7 vs 25.9 days, P =.19), nor did review quality (P =.39).\n Askfirst led to a higher rate of referee turndown than did justsend, but assenting askfirst referees completed reviews faster. The overall time for the review process did not differ between the 2 protocols.", "This study compared the editorial peer review experiences of authors who published in two groups of indexed U.S. medical journals. The study tested the hypothesis that after one journal rejects a manuscript an author selects a less well-known journal for submission. Group One journals were defined as those indexed in 1992 MEDLINE that satisfied several additional qualitative measures; Group Two journals were indexed in the 1992 MEDLINE only. Surveys were sent to the first authors of 616 randomly selected articles, and 479 surveys were returned, for a response rate of 78.1%. A total of 20.8% of Group One and 15.7% of Group Two articles previously had been rejected. Group One authors were more likely to select a journal for its prestige and article quality, while Group Two authors were more likely to have been invited to submit the manuscript. More than 60% of both groups felt the peer review had offered constructive suggestions, but that it had changed article conclusions less than 3% of the time. Both groups thought the review process only marginally improved content, organization, or statistical analysis, or clarified conclusions. Between 3% and 15% of all authors received considerable conflicting advice from different reviewers. Authors from both groups differed as to their reasons for journal selection, their connections with the publishing journal, and patterns of resubmission after rejection.", "All authors may not be equal in the eyes of reviewers. Specifically, well-known authors may receive less objective (poorer quality) reviews. One study at a single journal found a small improvement in review quality when reviewers were masked to author identity.\n To determine whether masking reviewers to author identity is generally associated with higher quality of review at biomedical journals, and to determine the success of routine masking techniques.\n A randomized controlled trial performed on external reviews of manuscripts submitted to Annals of Emergency Medicine, Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology.\n Two peers reviewed each manuscript. In one study arm, both peer reviewers received the manuscript according to usual masking practice. In the other arm, one reviewer was randomized to receive a manuscript with author identity masked, and the other reviewer received an unmasked manuscript.\n Review quality on a 5-point Likert scale as judged by manuscript author and editor. A difference of 0.5 or greater was considered important.\n A total of 118 manuscripts were randomized, 26 to usual practice and 92 to intervention. In the intervention arm, editor quality assessment was complete for 77 (84%) of 92 manuscripts. Author quality assessment was complete on 40 (54%) of 74 manuscripts. Authors and editors perceived no significant difference in quality between masked (mean difference, 0.1; 95% confidence interval [CI], -0.2 to 0.4) and unmasked (mean difference, -0.1; 95% CI, -0.5 to 0.4) reviews. We also found no difference in the degree to which the review influenced the editorial decision (mean difference, -0.1; 95% CI,-0.3 to 0.3). Masking was often unsuccessful (overall, 68% successfully masked; 95% CI, 58%-77%), although 1 journal had significantly better masking success than others (90% successfully masked; 95% CI, 73%-98%). Manuscripts by generally known authors were less likely to be successfully masked (odds ratio, 0.3; 95% CI, 0.1-0.8). When analysis was restricted to manuscripts that were successfully masked, review quality as assessed by editors and authors still did not differ.\n Masking reviewers to author identity as commonly practiced does not improve quality of reviews. Since manuscripts of well-known authors are more difficult to mask, and those manuscripts may be more likely to benefit from masking, the inability to mask reviewers to the identity of well-known authors may have contributed to the lack of effect.", "To compare the quality, presentation, readability, and clinical relevance of review articles published in peer-reviewed and \"throwaway\" journals.\n We reviewed articles that focused on the diagnosis or treatment of a medical condition published between January 1 and December 31, 1998, in the 5 leading peer-reviewed general medical journals and high-circulation throwaway journals. Reviewers independently assessed the methodologic and reporting quality, and evaluated each article's presentation and readability. Clinical relevance was evaluated independently by 6 physicians.\n Of the 394 articles in our sample, 16 (4.1%) were peer-reviewed systematic reviews, 135 (34.3%) were peer-reviewed nonsystematic reviews, and 243 (61.7%) were nonsystematic reviews published in throwaway journals. The mean (SD) quality scores were highest for peer-reviewed articles (0.94 [0.09] for systematic reviews and 0.30 [0.19] for nonsystematic reviews) compared with throwaway journal articles (0.23 [0.03], F(2,391) = 280.8, P<.001). Throwaway journal articles used more tables (P =.02), figures (P =.01), photographs (P<.001), color (P<.001), and larger font sizes (P<.001) compared with peer-reviewed articles. Readability scores were more often in the college or higher range for peer-reviewed journals compared with the throwaway journal articles (104 [77.0%] vs 156 [64.2%]; P =.01). Peer-reviewed article titles were judged less relevant to clinical practice than throwaway journal article titles (P<.001).\n Although lower in methodologic and reporting quality, review articles published in throwaway journals have characteristics that appeal to physician readers.", "Academic biomedical journals use peer review and editing to help to select and improve the quality of articles. We have investigated whether articles accepted by the Nederlands Tijdschrift voor Geneeskunde, the Dutch Journal of Medicine, were improved after peer review and editing (post-acceptance scientific and copy editing).\n 400 readers of the journal (100 each of medical students, recent medical graduates, general practitioners, and specialists) were invited to participate in a questionnaire survey. The first 25 from each group who agreed to participate were included. We posted a pack containing a set of identically appearing typescripts (ie, blinding) of the submitted, accepted, and published versions of 50 articles that had been published in Ned Tijdschr Geneeskd. Each evaluator received two of the sets of versions, and each set was evaluated by one person from each group. The package also included two questionnaires: the first was used to compare the submitted with the accepted version (25 questions), the second compared the accepted with the published version (17 questions). The questions were answered on five-point scales, and were about the quality of the articles or were general/overall scores. We analysed the data as scores of 3-5 (ie, improvement) versus 1-2.\n After peer review, the quality in 14 of 23 questions (61%) was significantly improved (p = 0.03 or smaller). In particular, the overall score and general medical value were significantly improved (p = 0.00001 for each). Editing led to significant improvement in 11 of 16 questions (69%, p = 0.017 or smaller), and especially in style and readability (p = 0.001 and p = 0.004). Generally, we found no differences between the scores of the four categories of evaluators. 72% of the evaluators correctly identified which version was which.\n Evaluations by readers of the Ned Tijdschr Geneeskd indicated significant improvement of published articles after both peer review and editing. We think that peer review and editing are worthwhile tasks. We also think that possible biases would have had a negligible effect on our results (including the fact that we selected the first 25 evaluators who responded, that some evaluators may have read the published version, and that one questionnaire may have looked more scientific than the other, more editorial one).", "To determine the effects of training on the quality of peer review.\n Single blind randomised controlled trial with two intervention groups receiving different types of training plus a control group.\n Reviewers at a general medical journal. Interventions Attendance at a training workshop or reception of a self taught training package focusing on what editors want from reviewers and how to critically appraise randomised controlled trials.\n Quality of reviews of three manuscripts sent to reviewers at four to six monthly intervals, evaluated using the validated review quality instrument; number of deliberate major errors identified; time taken to review the manuscripts; proportion recommending rejection of the manuscripts.\n Reviewers in the self taught group scored higher in review quality after training than did the control group (score 2.85 v 2.56; difference 0.29, 95% confidence interval 0.14 to 0.44; P = 0.001), but the difference was not of editorial significance and was not maintained in the long term. Both intervention groups identified significantly more major errors after training than did the control group (3.14 and 2.96 v 2.13; P < 0.001), and this remained significant after the reviewers' performance at baseline assessment was taken into account. The evidence for benefit of training was no longer apparent on further testing six months after the interventions. Training had no impact on the time taken to review the papers but was associated with an increased likelihood of recommending rejection (92% and 84% v 76%; P = 0.002).\n Short training packages have only a slight impact on the quality of peer review. The value of longer interventions needs to be assessed.", "Editorial management of articles on health economics may benefit from guidelines for peer review and revision.\n To assess whether publication (in August 1996) of the BMJ guidelines on peer review of economics submissions made any difference to editorial and peer review processes, quality of submitted manuscripts, and quality of published manuscripts.\n Before-after study conducted in the editorial offices of BMJ and The Lancet of the effect of the BMJ guidelines on review and revision of economics submissions, defined as those making explicit comments about resource allocation and/or costs of interventions.\n Editorial fate and changes in the quality of submissions.\n A total of 2982 manuscripts were submitted to the 2 journals during the before periods, 105 (3.5%) of which were economics submissions. Of these, 27 (24.3%) were full economics evaluations, and 78 (75.7%) were other economics submissions. Overall acceptance rate was 11.6% (12/105). During the after period 2077 manuscripts were submitted to the 2 journals, 87 (4.2%) of which were economics submissions. Eighteen (20.7%) were full economics evaluations, and 69 (79.3%) were other economics submissions. Overall acceptance rate was 6.9% (6/87). Although a number of manuscripts could not be traced to determine whether they were economics submissions, there appeared to be little difference between the 2 journals in numbers or editorial fate of the manuscripts. There was no change in the quality of submitted manuscripts, but BMJ editors found the guidelines and checklists useful and sent fewer economics submissions for external peer review in the after phase.\n Publication of the guidelines helped the BMJ editors improve the efficiency of the editorial process but had no impact on the quality of economics evaluations submitted or published.", "Peer review of medical papers is a confidential consultancy between the reviewer and the journal editor, and has been criticised for its potential bias and inadequacy. We explored the potential of the internet for open peer review to see whether this approach improved the quality and outcome of peer review.\n Research and review articles that had been accepted for publication in The Medical Journal of Australia (MJA) were published together with the reviewers' reports on the worldwide web, with the consent of authors and referees. Selected readers' e-mailed comments were electronically published as additional commentary; authors could reply or revise their paper in response to readers' comments. Articles were edited and published in print after this open review.\n 60 (81%) of 74 authors agreed to take part in the study, together with 150 (92%) of 162 reviewers. There was no significant difference in the performance of commissioned reviewers before and during the study. Four articles were not included because of insufficient time before print publication. Of the remaining 56 papers, 28 received 52 comments from 42 readers (2% of readers submitted comments). Most readers' comments were short and specific, and seven articles were changed by the authors in response.\n Open peer review is acceptable to most authors and reviewers. Postpublication review by readers on the internet is no substitute for commissioned prepublication review, but can provide editors with valuable input from individuals who would not otherwise be consulted. Readers also gain insight into the processes of peer review and publication.", "Study objective: We sought to determine whether peer reviewers who attend a formal interactive training session produce better reviews.\n Peer reviewers were invited to attend a formal, 4-hour, highly interactive workshop on peer review. Attendees received a sample manuscript to read and review in writing in advance. The workshop included presentations on analyzing a study and the journal's expectations for a quality review, discussion of the sample manuscript's flaws and how to address them in a review, discussion of the reviews written by the attendees, and discussion of real reviews of other manuscripts illustrating key points. The performance of attendees on the basis of standard editor quality ratings (1 to 5) was assessed for the 2 years after workshop attendance. Control reviewers matched for previous review quality and volume were selected from nonattendees of the workshop. In study 1, all average reviewers received a standard written invitation. In study 2, 75 randomly selected average reviewers were personally and actively recruited with intensive follow-up by means of e-mail and telephone calls in an effort to reduce self-selection bias.\n In study 1, 25 reviewers volunteered for the course, were eligible for study, attended, and were compared with 25 matched control reviewers. Of attendees filling out evaluations, 19% thought it somewhat and 81% thought it very helpful. All thought it would improve their subsequent reviews, and 85% thought it would improve their review ratings. The mean change in rating after the workshop was 0.11 (95% confidence interval [CI] -0.25 to 0.48) for control reviewers and 0.10 (95% CI -0.20 to 0.39) for attendees. In study 2, of 75 reviewers intensively recruited, only 12 (41%) of those who said they would attend did. All of the participants thought the workshop would improve their performance and ratings. Test scores at the end of the workshop improved in 73% of participants compared with scores on pretests. The control reviewers' average rating changed by -0.10 (95% CI -0.49 to 0.29) versus 0.06 (95% CI -0.34 to 0.23) for attendees.\n Among invited peer reviewers, voluntary attendance at a highly structured and interactive workshop was low and did not improve the quality of subsequent reviews, contrary to the predictions of attendees. Efforts to aggressively recruit average reviewers to a second workshop were time consuming, had low success rates, and showed a similar lack of effect on ratings, despite improvement in scores on a test instrument. Workshop teaching formats, although traditional, are of unproven efficacy.", "To evaluate the effects of peer review and editing on manuscript quality.\n Editorial offices of Annals of Internal Medicine.\n Masked before-after study. MANUSCRIPTS: 111 consecutive original research manuscripts accepted for publication at Annals between March 1992 and March 1993.\n We used a manuscript quality assessment tool of 34 items to evaluate the quality of the research report, not the quality of the research itself. Each item was scored on a 1 to 5 scale. Forty-four expert assessors unaware of the design or aims of the study evaluated the manuscripts, with different persons evaluating the two versions of each manuscript (before and after the editorial process).\n 33 of the 34 items changed in the direction of improvement, with the largest improvements seen in the discussion of study limitations, generalizations, use of confidence intervals, and the tone of conclusions. Overall, the percentage of items scored three or more increased by an absolute 7.3% (95% CI, 3.3% to 11.3%) from a baseline of 75%. The average item score improved by 0.23 points (CI, 0.07 to 0.39) from a baseline mean of 3.5. Manuscripts rated in the bottom 50% showed two- to threefold larger improvements than those in the top 50%, after correction for regression to the mean.\n Peer review and editing improve the quality of medical research reporting, particularly in those areas that readers rely on most heavily to decide on the importance and generalizability of the findings.", "The effects of methods used to improve the interrater reliability of reviewers' ratings of manuscripts submitted to the Journal of the American Academy of Child and Adolescent Psychiatry were studied.\n Reviewers' ratings of consecutive manuscripts submitted over approximately 1 year were first analyzed; 296 pairs of ratings were studied. Intraclass correlations and confidence intervals for the correlations were computed for the two main ratings by which reviewers quantified the quality of the article: a 1-10 overall quality rating and a recommendation for acceptance or rejection with four possibilities along that continuum. Modifications were then introduced, including a multi-item rating scale and two training manuals to accompany it. Over the next year, 272 more articles were rated, and reliabilities were computed for the new scale and for the scales previously used.\n The intraclass correlation of the most reliable rating before the intervention was 0.27; the reliability of the new rating procedure was 0.43. The difference between these two was significant. The reliability for the new rating scale was in the fair to good range, and it became even better when the ratings of the two reviewers were averaged and the reliability stepped up by the Spearman-Brown formula. The new rating scale had excellent internal consistency and correlated highly with other quality ratings.\n The data confirm that the reliability of ratings of scientific articles may be improved by increasing the number of rating scale points, eliciting ratings of separate, concrete items rather than a global judgment, using training manuals, and averaging the scores of multiple reviewers.", "Peer reviewers are blinded sometimes to authors' and institutions' names, but the effects of blinding on review quality are not known. We, therefore, conducted a randomized trial of blinded peer review. Each of 127 consecutive manuscripts of original research that were submitted to the Journal of General Internal Medicine were sent to two external reviewers, one of whom was randomly selected to receive a manuscript with the authors' and institutions' names removed. Reviewers were asked, but not required, to sign their reviews. Blinding was successful for 73% of reviewers. Quality of reviews was higher for the blinded manuscripts (3.5 vs 3.1 on a 5-point scale). Forty-three percent of reviewers signed their reviews, and blinding did not affect the proportion who signed. There was no association between signing and quality. Our study shows that, in our setting, blinding improves the quality of reviews and that research on the effects of peer review is possible.", "Anxiety about bias, lack of accountability, and poor quality of peer review has led to questions about the imbalance in anonymity between reviewers and authors.\n To evaluate the effect on the quality of peer review of blinding reviewers to the authors' identities and requiring reviewers to sign their reports.\n Randomized controlled trial.\n A general medical journal.\n A total of 420 reviewers from the journal's database.\n We modified a paper accepted for publication introducing 8 areas of weakness. Reviewers were randomly allocated to 5 groups. Groups 1 and 2 received manuscripts from which the authors' names and affiliations had been removed, while groups 3 and 4 were aware of the authors' identities. Groups 1 and 3 were asked to sign their reports, while groups 2 and 4 were asked to return their reports unsigned. The fifth group was sent the paper in the usual manner of the journal, with authors' identities revealed and a request to comment anonymously. Group 5 differed from group 4 only in that its members were unaware that they were taking part in a study.\n The number of weaknesses in the paper that were commented on by the reviewers.\n Reports were received from 221 reviewers (53%). The mean number of weaknesses commented on was 2 (1.7, 2.1, 1.8, and 1.9 for groups 1, 2, 3, and 4 and 5 combined, respectively). There were no statistically significant differences between groups in their performance. Reviewers who were blinded to authors' dentities were less likely to recommend rejection than those who were aware of the authors' identities (odds ratio, 0.5; 95% confidence interval, 0.3-1.0).\n Neither blinding reviewers to the authors and origin of the paper nor requiring them to sign their reports had any effect on rate of detection of errors. Such measures are unlikely to improve the quality of peer review reports.", "To determine whether attendance at a voluntary training workshop improves quality ratings of medical journal peer reviewers.\n Peer reviewers for Annals of Emergency Medicine who completed two or more reviews during the 20 months before or the 20 months after October 1995 were eligible. Reviews were routinely rated by editors on a subjective 5-point quality scale. Comparisons were made between reviewers who chose to attend a 4-hour workshop on peer review sponsored by the journal in 1995 (attendees) and 2 groups of reviewers who did not attend: controls matched for review quality and number of reviews completed before the workshop, and unmatched controls. Guest reviewers were excluded.\n A total of 298 reviewers completed 1906 reviews before the workshop and 2,194 after the workshop; 2,117 of these reviews were rated by editors. Forty-five attendees participated in the workshop, 39 of whom had sufficient ratings for analysis. Matched controls were almost identical in performance to attendees, but unmatched controls had performed fewer reviews and had lower average ratings before the workshop. There was no significant change in any performance measurement after the workshop, including average quality rating, percent change in quality rating, odds ratio for recommending acceptance, and odds ratio for congruence with editor's decision.\n In a self-selected group of experienced reviewers who attended a 4-hour workshop on peer review, no effect could be identified in subsequent performance as measured by editors' quality ratings or reviewer performance statistics.", "The statistical review of biomedical articles should result in an improved quality. The objective of this study was to compare the effects of clinical review and joint clinical and statistical review on manuscript quality, in articles submitted to Medicina Clínica (Barcelona), a Spanish weekly journal of internal medicine.\n Original papers arriving between May 2000 and February 2001 were randomized either to a clinical review group or a clinical and statistical review group. Two evaluators, blinded to the paper's group, assessed the quality improvement in both groups, from submission to publication using a modified version ot the Goodman et al. scale. The protocol required that final versions arrived before the end of May 2001.\n Final sample size was 43 manuscripts, evaluated before and after peer review. On the intention to treat analysis, the estimated effect of statistical review was 1.35 (95% CI: -0.45 to 3.16) positive, but not statistically significant. The analysis of the reviewers' comments revealed some protocol deviations. Taking into account the spontaneous inclusion of statistical experts in the clinical group, the estimated effect was statistically significant, with a confidence interval of 0.3 to 3.7.\n The inclusion of a statistical expert in the peer review process improves manuscript quality, although in the intention to treat analysis the improvement was not statistically significant.", "Most scientific journals practise anonymous peer review. There is no evidence, however, that this is any better than an open system.\n To evaluate the feasibility of an open peer review system.\n Reviewers for the British Journal of Psychiatry were asked whether they would agree to have their name revealed to the authors whose papers they review; 408 manuscripts assigned to reviewers who agreed were randomised to signed or unsigned groups. We measured review quality, tone, recommendation for publication and time taken to complete each review.\n A total of 245 reviewers (76%) agreed to sign. Signed reviews were of higher quality, were more courteous and took longer to complete than unsigned reviews. Reviewers who signed were more likely to recommend publication.\n This study supports the feasibility of an open peer review system and identifies such a system's potential drawbacks." ]

[ "1089885", "910806", "6697270", "320477", "6751183", "694487" ]

[ "Filtration leukapheresis for granulocyte transfusion therapy. Clinical and laboratory studies.", "A controlled study of the efficacy of granulocyte transfusions in patients with neutropenia.", "Pulmonary complications in patients receiving granulocyte transfusions and amphotericin B.", "A randomized clinical trial of granulocyte transfusions for infection in acute leukemia.", "Therapeutic granulocyte transfusions for documented infections. A controlled trial in ninety-five infectious granulocytopenic episodes.", "[Granulocyte substitution in febrile leukemia patients with bone marrow aplasia. 1. Results of a prospective study]." ]

[ "To study the clinical efficacy of granulocytes obtained by filtration leukapheresis, patients with clinically evident infection and granulocyte counts of smaller than 500 per cubic millimeter were randomly assigned to receive conventional therapy alone or with a granulocyte transfusion obtained from a single donor each day for four days. Five of 19 control patients survived to day 20, and 15 of 17 in the transfused group survived. Comparison of the two populations for variables such as age, disease, and severity and type of infection revealed no other factor that could account for the difference in survival. Outcome was not demonstrated to be related to HL-A match, post-transfusion counts, or presence of leukocyte antibodies. Functional studies of granulocytes obtained by filtration leukapheresis showed only minor differences although appearance was altered. Granulocytes so obtained can be used safely and efficaciously as adjunctive therapy for infection associated with granulocytopenia.", "A randomized clinical trial to determine the efficacy of granulocyte transfusions in neutropenic patients with infection was conducted. Criteria for patient selection included a proved infection, a granulocyte count of less than 300/mm3, availability of a suitable donor and failure to respond to at least 72 horus of appropriate antibiotic therapy. Thirty patients were assigned at random to receive either granulocyte transfusions or to serve as a control group. Antibiotic therapy was continued in both groups. Responses were judged by the degree of diminution of infectious episodes and survival. The results showed that 11 of 13 control patients failed to respond during the period of observation, whereas 10 of 17 patients given transfusions responded. The results were statistically significantly different (p less than 0.05). The median survival was 22.5 days in the group given transfusions (group 2) and 7.7 in the control group (group 1) (p less than 0.01). The granulocyte transfusions were most effective in patients with hypocellular marrows who failed to recover during the period of observation. These results indicate that granulocyte transfusions are effective in the short-term control of infections in neutropenic patients.", "To evaluate the possibility that in febrile granulocytopenic patients amphotericin B given along with granulocyte transfusions could increase the incidence of pulmonary complications, we studied 43 severely granulocytopenic patients during 46 episodes of fever. Granulocytes were administered as part of the clinical protocol to all 19 patients who had clinically or microbiologically documented infection; the other 24 patients were randomly allocated to treatment with granulocytes (13 patients) or without granulocytes (11 patients). In all, 32 patients received granulocyte transfusions during 35 episodes of fever. Pulmonary complications developed in six patients in each of the two randomized groups. The incidence of pulmonary complications was not influenced by the number of granulocyte transfusions or by the number of granulocytes per transfusion. Pulmonary complications were significantly more likely to occur in patients with fungal infections. Amphotericin B was given according to clinical indications; 21 patients in all received it. Survival was significantly poorer in patients with pulmonary complications, but the administration of amphotericin B was not related either to survival or to the incidence of pulmonary complications. We conclude that pulmonary complications and poor prognosis are related to underlying pulmonary fungal infection and not to any interaction between amphotericin B and granulocyte transfusions.", "In a prospective, controlled, randomized study to evaluate the efficacy of filtration-leukapheresis granulocytes in granulocytopenic, febrile patients with leukemia, 19 patients received antibiotics alone, and 12 received antibiotics plus daily granulocyte transfusions from ABO-matched donors. In skin-chamber studies the granulocytes appeared at sites of inflammation for at least six hours after transfusion. Infected subjects survived longer if they received granulocytes. Differences between control and transfused patients were greatest in patients with persistent bone-marrow failure, the 21-day survival being 20 per cent in controls, and 75 per cent in transfused patients. Granulocytes appeared to have no effect on the outcome of febrile episodes in which infection was not documented, the 21-day survival being 79 per cent for controls and 88 per cent for transfused patients. The transfusion of granulocytes thus appears to offer a survival advantage to infected, persistently granulocytopenic patients.", "Patients with granulocytopenia (granulocyte count less than 0.5 x 10(9)/L) and a documented infection were randomized to receive or not to receive daily granulocyte transfusions in addition to antimicrobial therapy. Thirty-four of 47 control patients responded to therapy compared to 30 of 48 transfused patients (type 2 error, pneumonia, or a soft tissue infection, respective response rates for the control and transfused patients were 11 of 11 and 11 of 16 (Yates' corrected chi-squared test, p = 0.12). Response rates for patients with gram-negative septicemia were lower but were influenced by recovery of bone marrow function. Eleven of 12 control patients and seven of seven transfused patients with recovery of marrow function survived the gram-negative septicemia. In contrast, 12 of 24 control patients and 12 of 25 transfused patients survived gram-negative septicemia and persistent granulocytopenia (type 2 error p = 0.13). Two thirds of all fatal infections were associated with an underlying disease refractory to medical therapy. Therapeutic granulocyte transfusions had no substantial benefit over optimal antimicrobial therapy alone in managing infected patients with granulocytopenia.", "A prospective, randomized study was performed in aplastic, granulocytopenic, infected patients with acute leukemia during induction therapy. 12 patients received antibiotics alone, and 13 received antibiotics plus 1.7-14.7 X 10(10) (MEAN 6.6 X 10(10) granulocytes by 1-5 (mean 2.7) daily transfusions. In 10 of 12 controls the infection resolved and remission was achieved with granulocyte counts greater than 500/mm3 15 +/- 9 days after randomization. In the transfused patients, infection was brought under control in 10 out of 13 and remission was achieved with granulocyte counts greater than 500/mm3 25+/- 11 days after randomization. Only one death due to infection was observed (6 days after randomization, control)." ]

[ "10378490", "17725472", "12605431", "2136991" ]

[ "Laser therapy: a randomized, controlled trial of the effects of low-intensity Nd:YAG laser irradiation on musculoskeletal back pain.", "In chronic low back pain, low level laser therapy combined with exercise is more beneficial than exercise alone in the long term: a randomised trial.", "Efficacy of low power laser therapy and exercise on pain and functions in chronic low back pain.", "Low-energy laser treatment and exercise for chronic low back pain: double-blind controlled trial." ]

[ "To assess the effectiveness of low-intensity laser therapy in the treatment of musculoskeletal low back pain.\n A double-masked, placebo-controlled, randomized clinical trial.\n A physical medicine and rehabilitation clinic.\n Sixty-three ambulatory men and women between the ages of 18 and 70yrs with symptomatic nonradiating low back pain of more than 30 days' duration and normal neurologic examination results.\n Subjects were bloc randomized into two groups with a computer-generated schedule. All underwent irradiation for 90 seconds at eight symmetric points along the lumbosacral spine three times a week for 4 weeks by a masked therapist. The sole difference between the groups was that the probes of a 1.06 microm neodymium:yttrium-aluminum-garnet laser emitted 542mW/cm2 for the treated subjects and were inactive for the control subjects.\n Subject's perception of benefit, level of function as assessed by the Oswestry Disability Questionnaire, and lumbar mobility.\n The treated group had a time-dependent improvement in two of the three outcome measures: perception of benefit and level of function. These results were most marked at the midpoint evaluation (p < .005, p < .01) and end of treatment (p < .017, p < .001) but tended to lessen at the 1-month follow-up (p < .10, p < .004). Lumbar mobility did not differ between the groups at any time. All tests were two-sample t tests with unequal variances.\n Treatment with low-intensity 1.06 microm laser irradiation produced a moderate reduction in pain and improvement in function in patients with musculoskeletal low back pain. Benefits, however, were limited and decreased with time. Further research is warranted.", "Is low level laser therapy an effective adjuvant intervention for chronic low back pain?\n Randomised trial with concealed allocation, blinded assessors and intention-to-treat analysis.\n Sixty-one patients who had low back pain for at least 12 weeks.\n One group received laser therapy alone, one received laser therapy and exercise, and the third group received placebo laser therapy and exercise. Laser therapy was performed twice a week for 6 weeks.\n Outcomes were pain severity measured using a 10-cm visual analogue scale, lumbar range of motion measured by the Schober Test and maximum active flexion, extension and lateral flexion, and disability measured with the Oswestry Disability Index on admission to the study, after 6 weeks of intervention, and after another 6 weeks of no intervention.\n There was no greater effect of laser therapy compared with exercise for any outcome, at either 6 or 12 weeks. There was also no greater effect of laser therapy plus exercise compared with exercise for any outcome at 6 weeks. However, in the laser therapy plus exercise group pain had reduced by 1.8 cm (95% CI 0.1 to 3.3, p = 0.03), lumbar range of movement increased by 0.9 cm (95% CI 0.2 to 1.8, p < 0.01) on the Schober Test and by 15 deg (95% CI 5 to 25, p < 0.01) of active flexion, and disability reduced by 9.4 points (95% CI 2.7 to 16.0, p = 0.03) more than in the exercise group at 12 weeks.\n In chronic low back pain low level laser therapy combined with exercise is more beneficial than exercise alone in the long term.", "The aim of this study was to determine whether low power laser therapy (Gallium-Arsenide) is useful or not for the therapy of chronic low back pain (LBP).\n This study included 75 patients (laser + exercise-25, laser alone-25, and exercise alone-25) with LBP. Visual analogue scale (VAS), Schober test, flexion and lateral flexion measures, Roland Disability Questionnaire (RDQ) and Modified Oswestry Disability Questionnaire (MODQ) were used in the clinical and functional evaluations pre and post therapeutically. A physician, who was not aware of the therapy undertaken, evaluated the patients.\n Significant improvements were noted in all groups with respect to all outcome parameters, except lateral flexion (P < 0.05).\n Low power laser therapy seemed to be an effective method in reducing pain and functional disability in the therapy of chronic LBP.\n Copyright 2003 Wiley-Liss, Inc.", "Twenty patients with chronic low back pain were enrolled in a randomized double-blind trial to test the efficacy of low-energy laser biostimulation combined with exercise. Ten patients received low-energy gallium-arsenide laser treatment, and ten received placebo laser treatment. Both groups were also placed on an active exercise program. Visual analogue and disability pain scores were assessed pretreatment and one month posttreatment and showed significant (p less than .02) improvements in both groups, but no relative advantage was found for either group. Objective parameters using computerized triaxial measurements of range of motion, isometric torque, and isodynamic velocity were also performed before and after treatment. There were significant improvements in objective parameters in both the laser and placebo groups, but no relative advantage accrued to either group. Under the conditions of this study, low-energy laser stimulation plus exercise did not provide a significant advantage over exercise alone." ]

[ "12819517", "17786128", "15905743", "15909273", "11872998", "12441803" ]

[ "Therapeutic drug monitoring of nelfinavir and indinavir in treatment-naive HIV-1-infected individuals.", "A randomized controlled trial of therapeutic drug monitoring in treatment-naive and -experienced HIV-1-infected patients.", "Therapeutic drug monitoring of nevirapine reduces pharmacokinetic variability but does not affect toxicity or virologic success in the ATHENA study.", "A randomized controlled trial to evaluate antiretroviral salvage therapy guided by rules-based or phenotype-driven HIV-1 genotypic drug-resistance interpretation with or without concentration-controlled intervention: the Resistance and Dosage Adapted Regimens (RADAR) study.", "Concentration-controlled compared with conventional antiretroviral therapy for HIV infection.", "PharmAdapt: a randomized prospective study to evaluate the benefit of therapeutic monitoring of protease inhibitors: 12 week results." ]

[ "Both virological failure and the toxicity of HIV protease inhibitors have been related to interindividual variability of plasma drug concentrations. Therapeutic drug monitoring (TDM) offers the possibility to detect patients with drug concentrations outside therapeutic ranges, who can subsequently benefit from dose modifications.\n ATHENA was a randomized controlled clinical trial. Subjects were randomly assigned to either a TDM group, in which the results of drug concentration measurements plus advice were reported to their treating physician, or to a control group for whom TDM results were not reported. This analysis refers to treatment-naive patients who started a regimen containing indinavir or nelfinavir before November 1999.\n A total of 147 patients were randomly assigned: 92 to nelfinavir, 55 to indinavir. After one year of follow-up significantly fewer patients in the TDM group had discontinued nelfinavir or indinavir than in the control group: 17.4 versus 39.7%. This was mainly driven by a significantly lower rate of discontinuation because of virological failure in nelfinavir patients: 2.4% in the TDM group versus 17.6% in the control group, and by a non-significant difference in the rate of discontinuation because of toxicity in indinavir patients: 14.3% in the TDM group versus 29.6% in the control group. In a non-completer equals failure analysis of all randomized patients, the TDM group showed a significantly higher proportion of patients with a viral load below 500 copies after 12 months of treatment (78.2 versus 55.1%).\n TDM of nelfinavir and indinavir in treatment-naive patients improves treatment response.", "To improve the utility of therapeutic drug monitoring (TDM) by defining the proportion of patients with and predictors of above or below target protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) concentrations.\n This 48-week, multicenter, open-label clinical trial randomized patients to TDM versus standard of care (SOC). Serial pharmacokinetics, including a week-2 3-sample sparse collection, and expert committee TDM recommendations were given to TDM-arm patients' providers.\n Seventy-four (39%) of 190 patients had week-2 concentrations outside of targets and 122 (64%) of 190 had nontarget exposure at least once over 48 weeks. Providers accepted 75% of TDM recommendations. Among patients with below-target concentrations, more TDM-arm than SOC-arm patients achieved targets (65% vs. 45%; P = 0.09). Increased body weight and efavirenz or lopinavir/ritonavir use were significant predictors of nontarget concentrations. Patients at target and patients who achieved targets after TDM-directed dose modifications trended toward greater viral load reductions at week 48 than patients with below-target exposures (HIV RNA reductions: 2.4, 2.3, and 1.9 log10 copies/mL, respectively; P = 0.09).\n Most patients had nontarget PI and/or NNRTI concentrations over 48 weeks. TDM recommendations were well accepted and improved exposure. Patients below TDM targets trended toward worse virologic response.", "nan", "It is not well defined whether concentration-controlled intervention (CCI) and rules-based human immunodeficiency virus (HIV) type 1 genotype drug-resistance interpretation (GI) or virtual phenotype drug-resistance interpretation (VPI) may improve the outcome of HIV salvage therapy.\n In a prospective, randomized, controlled trial, patients were randomized (on a factorial basis) to change treatment after either GI or VPI, and they then were further randomized to the control arm (no CCI) or the CCI arm. Protease inhibitor (PI) and nonnucleoside reverse-transcriptase inhibitor (NNRTI) trough concentration (Ctrough) values were determined at weeks 1, 4, 12, and 24 of the study.\n Among 230 patients, virological benefit (defined by an HIV RNA load of <400 copies/mL at week 24) was not statistically different, either between patients in the GI and VPI arms or between patients in the CCI and control arms. A virological benefit was found for patients in the CCI arm, compared with patients in the control arm, but this benefit was not statistically significant (56.8% vs. 64.3% at week 4 and 63.6% vs. 74% at week 12). Dosage adaptation was possible for only a fraction of patients, because of low rates of treatment adherence or patient refusal to increase dosages. In the logistic regression analysis, independent predictors of virological response at week 24 were a PI Ctrough value and/or an NNRTI Ctrough value in the higher quartiles (or above cutoff levels) and a low number of PIs previously received. Moreover, receipt of a regimen that contained PIs boosted with ritonavir was an independent predictor of virological response.\n The present study did not support the routine use of CCI for patients undergoing salvage treatment, probably as a result of existing difficulties associated with its clinical application. However, a higher Ctrough value appeared to be correlated with treatment response. No major differences were found between VPI or GI when they are used together with expert advice for the selection of salvage treatment combinations.", "To demonstrate the feasibility of a concentration-controlled approach to combination antiretroviral therapy, and to compare the virological responses and safety of this strategy versus conventional fixed-dose therapy.\n A prospective, randomized, 52 week, open-label trial of concentration-controlled compared with conventional dose zidovudine, lamivudine, and indinavir therapy conduced in a university-based general clinical research center in the United States.\n Forty antiretroviral-naive individuals with plasma HIV-RNA levels > 5000 copies/ml.\n Zidovudine, lamivudine, and indinavir plasma concentrations were measured in all participants. Doses were adjusted in those assigned to concentration-controlled therapy to achieve levels equal to or greater than target values.\n The proportion of patients who achieved the desired drug concentrations, the proportion of patients with HIV-RNA levels < 50 copies/ml at week 52, and safety and tolerance in the concentration-controlled versus conventional therapy arms.\n Significantly more concentration-controlled recipients achieved the desired concentration targets for all three drugs: 15 of 16 concentration-controlled recipients compared with nine of 17 conventional recipients (P = 0.017) had HIV-RNA levels < 50 copies/ml at week 52. No difference was observed in the occurrence of drug-related clinical events or laboratory abnormalities between the two treatment arms.\n Concentration-controlled therapy implemented simultaneously for three antiretroviral agents was feasible, as well tolerated as conventional therapy, and resulted in a greater proportion of recipients with HIV-RNA levels < 50 copies/ml after 52 weeks. These findings provide a scientific basis to challenge the accepted practice of administering the same dose of antiretroviral agents to all adults, ignoring the concentrations actually achieved.", "A randomized study to evaluate the usefulness of protease inhibitor (PI) therapeutic drug monitoring (TDM) in antiretroviral-experienced HIV-infected patients.\n In the control arm, treatment was modified according to genotypic resistance testing. In the TDM arm, therapy was modified on the basis of genotypic resistance testing and at week 8 according to PI plasma trough levels measured at week 4. The major endpoint was the change in HIV-RNA levels at week 12.\n A total of 183 patients, 96 in the control arm and 87 in the TDM arm, were included in the study. Low-dose ritonavir to enhance the associated PI was prescribed to 62.5% of patients in the control arm and 65.5% of patients in the TDM arm. Using our PI concentration targets, 17/81 patients (21%) in the TDM arm were considered to have suboptimal or partly optimal PI plasma levels at week 4. Physician and protocol-driven PI modifications were performed in 18/85 patients (23.5%) in the TDM arm, and in seven of 94 patients (7%) in the control arm (P < 0.01). Week 12 HIV RNA dropped 2 log10 copies/ml in the control arm and 1.7 log10 copies/ml in the TDM arm, respectively.\n We found no statistically significant difference between the TDM arm and control arm in virological outcome at week 12. The utility of TDM could be dependent on the presence of low-dose ritonavir as a booster and the antiretroviral experience of the studied population. Effective non-toxic target concentrations for resistant viruses have still to be determined.\n Copyright 2002 Lippincott Williams & Wilkins" ]

[ "9668994" ]

[ "The effect of extraction of third molars on late lower incisor crowding: a randomized controlled trial." ]

[ "The problem of late mandibular incisor crowding is a well established phenomenon, the cause of which has been the substance of considerable debate over the years. A central issue is the possible role of the third molars though no definitive conclusions have been consistently drawn. This prospective study was designed to investigate the effects of randomly assigned early extraction of third molars on late crowding of the mandibular incisors. One-hundred-and-sixty-four patients entered the study from 1984 following completion of retention after orthodontic treatment. Seventy-seven patients (47%) returned for records up to a mean of 66 months later, and their start and finish study casts were digitized on a reflex microscope to determine Little's index of irregularity, intercanine width and arch length. Forty-four of the patients had been randomized to have third molars removed. There was no evidence of responder bias. Where third molars were extracted the mean increase in lower labial segment irregularity was reduced by 1.1 mm from a mean of 2.1 mm for the group where third molars were retained (P = 0.15, not statistically significant). This difference was also not considered to be clinically significant. The principal conclusion drawn from this randomized prospective study is that the removal of third molars to reduce or prevent late incisor crowding cannot be justified." ]

[ "11343530", "11742045", "10474848", "9068685", "7059922", "12464834", "7235853" ]

[ "Supportive-expressive group therapy and distress in patients with metastatic breast cancer: a randomized clinical intervention trial.", "The effect of group psychosocial support on survival in metastatic breast cancer.", "A group cognitive behaviour therapy programme with metastatic breast cancer patients.", "Problem-solving therapy in palliative care.", "Effects of counseling for late stage cancer patients.", "Relaxation and imagery for anxiety and depression control in community patients with advanced cancer.", "Group support for patients with metastatic cancer. A randomized outcome study." ]

[ "Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control.\n Of 125 women with metastatic breast cancer recruited into the study, 64 were randomized to the intervention and 61 to the control condition. Intervention women were offered 1 year of weekly supportive-expressive group therapy and educational materials. Control women received educational materials only. Participants were assessed at baseline and every 4 months during the first year. Data at baseline and from at least 1 assessment were collected from 102 participants during this 12-month period, and these participants compose the study population.\n Primary analyses based on all available data indicated that participants in the treatment condition showed a significantly greater decline in traumatic stress symptoms on the Impact of Event Scale (effect size, 0.25) compared with the control condition, but there was no difference in Profile of Mood States total mood disturbance. However, when the final assessment occurring within a year of death was removed, a secondary analysis showed a significantly greater decline in total mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size, 0.33) for the treatment condition compared with the control condition.\n Supportive-expressive therapy, with its emphasis on providing support and helping patients face and deal with their disease-related stress, can help reduce distress in patients with metastatic breast cancer.", "Supportive-expressive group therapy has been reported to prolong survival among women with metastatic breast cancer. However, in recent studies, various psychosocial interventions have not prolonged survival.\n In a multicenter trial, we randomly assigned 235 women with metastatic breast cancer who were expected to survive at least three months in a 2:1 ratio to an intervention group that participated in weekly supportive-expressive group therapy (158 women) or to a control group that received no such intervention (77 women). All the women received educational materials and any medical or psychosocial care that was deemed necessary. The primary outcome was survival; psychosocial function was assessed by self-reported questionnaires.\n Women assigned to supportive-expressive therapy had greater improvement in psychological symptoms and reported less pain (P=0.04) than women in the control group. A significant interaction of treatment-group assignment with base-line psychological score was found (P</=0.003 for the comparison of mood variables; P=0.04 for the comparison of pain); women who were more distressed benefited, whereas those who were less distressed did not. The psychological intervention did not prolong survival (median survival, 17.9 months in the intervention group and 17.6 months in the control group; hazard ratio for death according to the univariate analysis, 1.06 [95 percent confidence interval, 0.78 to 1.45]; hazard ratio according to the multivariate analysis, 1.23 [95 percent confidence interval, 0.88 to 1.72]).\n Supportive-expressive group therapy does not prolong survival in women with metastatic breast cancer. It improves mood and the perception of pain, particularly in women who are initially more distressed.", "One-hundred and twenty-four patients with metastatic breast cancer were randomised to either a group Cognitive Behaviour Therapy (CBT) intervention, or to a no-therapy control group condition. Both groups received standard oncological care; however, therapy recipients also attended eight weekly sessions of group CBT, followed by a family night, and three further monthly sessions. Patients completed the 'Profile of Mood States' (POMS) and the Coopersmith Self-esteem Inventory (CSI) before and after therapy, and at 3 and 6 month follow-up periods. Outcome data in the period following therapy showed reduced depression and total mood disturbance, as well as improved self-esteem amongst therapy participants, relative to a no-therapy control group. These improvements were no longer evident at the 3 or 6 month follow-up assessments. We also report on the difficulties associated with conducting a group intervention with this patient cohort.", "Emotional syndromes of depression and anxiety are common among palliative care patients. This pilot study evaluated the feasibility and acceptability of using a brief psychological treatment (problem-solving therapy) to treat these syndromes in patients receiving palliative care. Results were encouraging, particularly as regards acceptability to patients. Problems encountered during the study are discussed in the context of planning future research into the efficacy of treatments for emotional disorders in palliative care.", "Much has been written about working with the dying. Few, if any, controlled studies have examined the application of principles set forth. The authors evaluate the effectiveness of working with dying cancer patients by assessing changes in quality of life, physical functioning, and survival. One-hundred twenty men with end-stage cancer were randomly assigned to experimental or control groups; the 62 experimental group patients were seen regularly by a counselor. Patients were assessed before random assignment and at one, three, six, nine, and 12 months on quality of live and functional status. Experimental group patients improved significantly more than the control group on quality of life within three months. Functional status and survival did not differ between groups. A subsample of lung cancer patients provided cross-validation of findings. Although survival was not expected to differ, it was predicted that functioning would be enhanced if quality of life improved. One interpretation is that little can be done to alter physical function and survival when intervention occurs late in the progression of a fatal disease. This in no way reduces the value of improving overall quality of life, since enhancing the quality of survival for end-stage cancer patients is a high priority medical goal.", "A community-based nursing study was conducted in Sydney, Australia, to compare the effects of progressive muscle relaxation and guided imagery on anxiety, depression, and quality of life in people with advanced cancer. In this study, 56 people with advanced cancer who were experiencing anxiety and depression were randomly assigned to 1 of 4 treatment conditions: (1) progressive muscle relaxation training, (2) guided imagery training, (3) both of these treatments, and (4) control group. Subjects were tested before and after learning muscle relaxation and guided imagery techniques for anxiety, depression, and quality of life using the Hospital Anxiety and Depression scale and the Functional Living Index-Cancer scale. There was no significant improvement for anxiety; however, significant positive changes occurred for depression and quality of life.", "The effects of weekly supportive group meetings for women with metastatic carcinoma of the breast were systematically evaluated in a one-year, randomized, prospective outcome study. The groups focused on the problems of terminal illness, including improving relationships with family, friends, and physicians and living as fully as possible in the face of death. We hypothesized that this invention would lead to improved mood, coping strategies, and self-esteem among those in the treatment group. Eighty-six patients were tested at four-month intervals. The treatment group had significantly lower mood-disturbance scores on the Profile of Mood States scale, had fewer maladaptive coping responses, and were less phobic than the control group. This study provides objective evidence that a supportive group intervention for patients with metastatic cancer results in psychological benefit. Mechanisms underlying the effectiveness of this group intervention are explored." ]

[ "2200559" ]

[ "Prospective randomized controlled trial of hepatic arterial embolization or infusion chemotherapy with 5-fluorouracil and degradable starch microspheres for colorectal liver metastases." ]

[ "Survival benefit from hepatic artery embolization (HAE) or hepatic arterial infusion chemotherapy (HAI) in patients with unresectable colorectal liver metastases has not previously been assessed in a randomized controlled trial. Sixty-one patients were randomized, 20 to receive no treatment, 22 to receive HAE, and 19 to receive HAI with 5-fluorouracil and degradable starch microspheres. Both treatments were acceptable to the patients in terms of low treatment morbidity rate. Median survival from diagnosis of metastases was 9.6 months for controls, 8.7 months for the HAE group and 13.0 months in the HAI group. There was no apparent survival benefit for the HAE group. The increased survival in the HAI group was observed in all the subgroups analysed but failed to reach statistical significance. The greatest observed benefit was achieved in the subgroup with less than 50 per cent hepatic replacement with tumour at presentation (median survival from diagnosis 10.0 months for controls, 10.2 months for HAE and 23.6 months for HAI); 36 per cent of patients developed extrahepatic disease recurrence. No significant benefit has been shown from either HAE or HAI, but a more carefully selected group of patients with only low volume hepatic disease may benefit from HAI therapy." ]

[ "3537248", "2538521", "3009633", "10440305", "2842405", "2541168", "8699054", "2154925", "2884455", "8046423", "9337376", "7491235", "1995721", "8545227", "9652561", "1663261", "1321858", "1650128", "2554244", "12126907", "2845349", "2821477", "2330930", "1852084", "1651610", "1662796", "2172394", "7603812", "3031574", "2164706", "9607059", "2161038", "1975333", "11793395", "8408569", "8920706", "2890003", "11740320", "9002329", "6143964", "8933551", "8245557", "3033593", "2848432", "2157737", "2160516", "8393606", "2162027", "2852792", "2873370", "7707626", "2536789", "9323616", "1326741", "10418923", "2545451", "9386673", "3009634", "3894608", "10426173" ]

[ "Safety and immunogenicity of bovine rotavirus vaccine RIT 4237 in 3-month-old infants.", "Prolonged efficacy of rhesus rotavirus vaccine in Swedish children.", "Evaluation of rhesus rotavirus vaccine (MMU 18006) in infants and young children.", "Efficacy of live, attenuated, human rotavirus vaccine 89-12 in infants: a randomised placebo-controlled trial.", "Protective effect of WC3 vaccine against rotavirus diarrhea in infants during a predominantly serotype 1 rotavirus season.", "Reactions to and antigenicity of two human-rhesus rotavirus reassortant vaccine candidates of serotypes 1 and 2 in Venezuelan infants.", "Safety, immunogenicity, and protective efficacy of one and three doses of the tetravalent rhesus rotavirus vaccine in infants in Lima, Peru.", "Rhesus Rotavirus candidate vaccine. Clinical trial in children vaccinated between 2 and 5 months of age.", "Trial of an attenuated bovine rotavirus vaccine (RIT 4237) in Gambian infants.", "Evaluation of the antigenicity and reactogenicity of varying formulations of the rhesus rotavirus-based quadrivalent and the M37 rotavirus vaccine candidates.", "Efficacy of the rhesus rotavirus-based quadrivalent vaccine in infants and young children in Venezuela.", "Comparison of immunogenicity and efficacy of rhesus rotavirus reassortant vaccines in breastfed and nonbreastfed children. US Rotavirus Vaccine Efficacy Group.", "A field study of the safety and efficacy of two candidate rotavirus vaccines in a Native American population.", "Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines--report of the National Multicenter Trial. United States Rotavirus Vaccine Efficacy Group.", "Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis.", "Evaluation of the efficacy of a low-passage bovine rotavirus (strain WC3) vaccine in children in Central Africa.", "Field trial of rhesus rotavirus or human-rhesus rotavirus reassortant vaccine of VP7 serotype 3 or 1 specificity in infants. The Elmwood, Panorama, and Westfall Pediatric Groups.", "Immunogenicity of tetravalent rhesus rotavirus vaccine administered with buffer and oral polio vaccine.", "Simultaneous administration of rhesus rotavirus vaccine and oral poliovirus vaccine: immunogenicity and reactogenicity.", "Early phase II trial of human rotavirus vaccine candidate RV3.", "Field trial of rhesus rotavirus vaccine in infants.", "Candidate rotavirus vaccine (rhesus rotavirus strain) in children: an evaluation.", "An efficacy trial of the rhesus rotavirus vaccine in Maryland. The Clinical Study Group.", "Efficacy of two doses of RIT 4237 bovine rotavirus vaccine for prevention of rotavirus diarrhoea.", "Immunogenicity and safety of rhesus-human rotavirus reassortant vaccines with serotype 1 or 2 VP7 specificity.", "Evaluation of the M37 human rotavirus vaccine in 2- to 6-month-old infants.", "Evaluation of WC3 rotavirus vaccine and correlates of protection in healthy infants.", "Evaluation of the protective efficacy of a serotype 1 bovine-human rotavirus reassortant vaccine in infants.", "Neonatal rotavirus vaccination with RIT 4237 bovine rotavirus vaccine: a preliminary report.", "Evaluation of RIT 4237 bovine rotavirus vaccine in newborn infants: correlation of vaccine efficacy to season of birth in relation to rotavirus epidemic period.", "Safety and immunogenicity of live, attenuated human rotavirus vaccine 89-12.", "Immune protection of infants against rotavirus gastroenteritis by a serotype 1 reassortant of bovine rotavirus WC3.", "Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesus-rotavirus-based quadrivalent vaccine.", "Clinical evaluation of a single oral dose of human-bovine (UK) reassortant rotavirus vaccines Wa x UK (P1A[8],G6) and Wa x (DS-1 x UK) (P1A[8],G2).", "Reactogenicity and immunogenicity of a high-titer rhesus rotavirus-based quadrivalent rotavirus vaccine.", "Immunogenicity, safety and protective efficacy of one dose of the rhesus rotavirus vaccine and serotype 1 and 2 human-rhesus rotavirus reassortants in children from Lima, Peru.", "Live attenuated oral rotavirus vaccine.", "Safety and immunogenicity of tetravalent rhesus-based rotavirus vaccine in Bangladesh.", "Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant rotavirus vaccine in Belém, Brazil.", "Protection of infants against rotavirus diarrhoea by RIT 4237 attenuated bovine rotavirus strain vaccine.", "Comparative evaluation of reactogenicity and immunogenicity of two dosages of oral tetravalent rhesus rotavirus vaccine. US Rhesus Rotavirus Vaccine Study Group.", "Evaluation of a bovine-human rotavirus reassortant vaccine in infants.", "Immunogenicity and reactogenicity of lowered doses of rhesus rotavirus vaccine strain MMU 18006 in young children.", "[Oral vaccination with live attenuated rotavirus].", "Clinical studies of a quadrivalent rotavirus vaccine in Venezuelan infants.", "Prospective study of diarrheal diseases in Venezuelan children to evaluate the efficacy of rhesus rotavirus vaccine.", "A comparative evaluation of the safety and immunogenicity of a single dose of unbuffered oral rhesus rotavirus serotype 3, rhesus/human reassortant serotypes 1, 2 and 4 and combined (tetravalent) vaccines in healthy infants.", "Effect of dose and a comparison of measures of vaccine take for oral rhesus rotavirus vaccine. The Maryland Clinical Studies Group.", "Reactogenicity and antigenicity of rhesus rotavirus vaccine (MMU-18006) in newborn infants in Venezuela.", "Failure of live, attenuated oral rotavirus vaccine.", "Evaluation of rhesus rotavirus monovalent and tetravalent reassortant vaccines in US children. US Rotavirus Vaccine Efficacy Group.", "Protection of Peruvian children against rotavirus diarrhea of specific serotypes by one, two, or three doses of the RIT 4237 attenuated bovine rotavirus vaccine.", "Phase 1 trial of a candidate rotavirus vaccine (RV3) derived from a human neonate.", "Protective efficacy against serotype 1 rotavirus diarrhea by live oral rhesus-human reassortant rotavirus vaccines with human rotavirus VP7 serotype 1 or 2 specificity.", "Safety and immunogenicity of live attenuated human-bovine (UK) reassortant rotavirus vaccines with VP7-specificity for serotypes 1, 2, 3 or 4 in adults, children and infants.", "A trial of RIT-4237 rotavirus vaccine in 1-month-old infants.", "Efficacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations.", "A comparative trial of rhesus monkey (RRV-1) and bovine (RIT 4237) oral rotavirus vaccines in young children.", "Clinical efficacy of the RIT 4237 live attenuated bovine rotavirus vaccine in infants vaccinated before a rotavirus epidemic.", "Concurrent administration of rhesus rotavirus tetravalent (RRV-TV) vaccine with pentavalent diphtheria-pertussis-tetanus-Haemophilus influenzae beta-inactivated polio and hepatitis B vaccines." ]

[ "To assess the safety and immunogenicity of bovine rotavirus vaccine, we administered attenuated strain RIT 4237 to 54 inner-city infants randomized to one of three groups in a double-blind fashion to receive a dose at 3 and 5 months of age of either placebo, vaccine virus at 10(7) TCID50/ml, or vaccine virus at 10(8) TCID50/ml. Vaccination began in early fall 1984, and continued through spring 1985. Forty-nine infants received one dose of vaccine or placebo; 43 received both doses of vaccine or placebo. At 2 and 3 months after vaccination, homologous geometric mean neutralizing antibody titers were significantly higher in children who received either dose of vaccine compared with placebo recipients. Cumulative seroconversion to bovine rotavirus after either dose of vaccine virus was 87% at 6 months of age. Seroconversion was significantly higher (P less than 0.01) in both vaccine groups compared with the placebo group. No ill effects were associated with vaccine administration. RIT 4237 vaccine appears to be safe and immunogenic when administered to young infants living in the United States.", "nan", "Orally administered rhesus rotavirus vaccine was evaluated in a placebo-controlled study in young children and infants (ages, eight months to 61 months). Thirteen children received the rotavirus vaccine, and ten children served as the control group. The vaccine was well tolerated. There were no significant differences between the vaccine recipients and the control group in the number of child-days with temperatures greater than or equal to 37.8 C, vomiting, diarrhea, or cough. There were significantly more child-days of rhinorrhea among the vaccine recipients than there were among the control group. The vaccine recipients under two years of age passed a larger number of stools than did the children in the control group, and vaccine recipients had significantly more semiformed and unformed stools than did the children receiving the placebo. All twelve of the children tested were positive for viral shedding. Peak viral shedding occurred on days three and five postvaccination. On day eight, over one-half of the children from whom a stool specimen was obtained were still shedding rotavirus. Children less than two years old shed more rotavirus in their stool than did children more than two years old. All 13 vaccine recipients had a fourfold or greater rise in titer of antibody as measured by plaque reduction, tube neutralization, complement fixation, and/or immune adherence hemagglutination.", "Rotavirus is the most common cause of severe, dehydrating diarrhoea in infants worldwide. We assessed the safety, immunogenicity, and efficacy of a live, oral human rotavirus vaccine, 89-12, in US children in a randomised, placebo-controlled, double-blind multicentre trial.\n 215 healthy infants were enrolled, of whom 213 were given two doses of 89-12 (containing 1x10(5) plaque-forming units) or placebo, and 213 were followed up through one rotavirus season. The frequency of side-effects was compared for 7 days after each dose of vaccine. Immune responses to rotavirus were assessed by serum and stool IgA, and by serum 89-12 neutralising titres. The primary outcome variable (protection from rotavirus disease) was evaluated by comparing the frequencies of rotavirus gastroenteritis in an intention-to-treat analysis.\n Adverse reactions were mild. Low-grade fever (> or = 38.1 degrees C) after the first dose was the only side-effect significantly more common in the vaccine group than in the placebo group (21 [19%] vs 5 [5%], p=0.001). An immune response to vaccine was detected in 94.4% of vaccinees. Rotavirus disease occurred in 18 of 107 placebo recipients and two of 108 vaccine recipients (vaccine efficacy 89.0% [95% CI 65.4-94.5]). Ten infants in the placebo group but none in the vaccine group were presented for medical care.\n The 89-12 rotavirus vaccine was safe and immunogenic and provided a high degree of protection against rotavirus disease. Further investigations of this vaccine are needed to confirm these findings in other settings.", "We used a double-blind, placebo-controlled trial to study the efficacy of WC3 rotavirus vaccine administered to 104 infants (ages, three to 12 months) before the rotavirus season. Forty-nine infants received vaccine; 55 received placebo. Rotavirus disease during this season was predominantly caused by a serotype 1 strain. In placebo recipients there were 14 cases of rotavirus diarrhea (attack rate, 25%); 11 were moderate to severe (attack rate, 20%). Vaccinees experienced only three cases of rotavirus disease (attack rate, 6.1%), all mild. When all cases (whether associated with rotavirus or not) of clinically significant diarrhea (CSD) were evaluated, WC3 vaccine provided statistically significant (P less than .01) protection against the total number of episodes of CSD and reduced the number of days of CSD-associated diarrhea, vomiting, fever, or illness. Seventy-one percent of the WC3-vaccinated infants had serum antibody responses to the vaccine. The 14 placebo recipients who experienced natural disease predominantly had antibody responses to serotype 1. Sera taken after the rotavirus season revealed a nearly identical rate (40%) of natural rotavirus infection in the vaccinated and placebo groups.", "The reactions to and antigenicity of two human-rhesus rotavirus (RRV) reassortants (human rotavirus strain D x RRV and human rotavirus strain DS1 x RRV) with the VP7 neutralization specificity of a serotype 1 or serotype 2 rotavirus were evaluated in a placebo-controlled double-blind trial in 116 1- to 5-month-old infants in Caracas, Venezuela. The children were randomly divided into five groups to receive orally the following inocula: (i) 10(4) PFU of D x RRV reassortant; (ii) 10(4) PFU of DS1 x RRV reassortant; (iii) 10(4) PFU of RRV; (iv) 5 x 10(3) PFU of D x RRV and 5 x 10(3) PFU of RRV; and (v) placebo. The children were examined daily for 7 days following vaccine administration; 8 to 26% of the vaccinated infants developed a mild febrile reaction which in most cases lasted only 1 day. Seroresponses to rotavirus were observed in 39 to 65% of the vaccinees by plaque neutralization assay and in 57 to 88% by an immunoglobulin A enzyme-linked immunosorbent assay. Vaccine shedding was detected in 53 to 86% of the vaccinees. Analysis of neutralization antibody responses indicates that the VP4 protein represents an important component of the response induced by the vaccines.", "An oral rhesus-human rotavirus tetravalent (RRV-TV) vaccine (10(4) pfu of rhesus rotavirus [type G3] and of 3 human-rhesus reassortants [G1, G2, and G4]) was evaluated in a field trial in Lima, Peru. At 2, 3, and 4 months of age, infants received either a dose of RRV-TV, an initial dose of vaccine followed by a dose of placebo at 3 and 4 months, or a dose of placebo. Rotavirus-specific IgA responses were detected by ELISA in 75% of the three-dose vaccine group, 59% of the one-dose vaccine group (P = .05), and 24% of the placebo group (P < .001): 64%, 48%, and 12% of each group, respectively, had a neutralizing antibody response to at least 1 serotype. Both one and three doses of vaccine failed to induce a significant level of protection against rotavirus diarrhea; however, they did provide some protection (range, 35%-66%) against more severe rotavirus diarrhea, especially for episodes caused by type G1.", "Live attenuated oral rhesus Rotavirus candidate vaccine (strain MMU 18006 [lot RRV-1]) was evaluated for immunogenicity, safety, and clinical protection in a double-blind, placebo-controlled trial involving 200 infants aged 2 to 5 months when vaccinated. Vaccine-induced fourfold or greater rise of Rotavirus antibodies was seen in 62% of the infants. Febrile reactions of short duration on days 3 and/or 4 after vaccination occurred in 26% of the vaccine recipients. The clinical follow-up covered two Rotavirus seasons, in which serotypes 1 and 4 were prevalent. There were 16 cases of confirmed Rotavirus diarrhea in the placebo-treated group and 10 in the vaccine-treated group; from this a vaccine protection rate of 38% was derived. Clinical severity of Rotavirus diarrhea was assessed by a score; 13 cases in the placebo-treated group and 5 in the vaccine-treated group were regarded as severe or moderately severe, giving a vaccine protection rate of 67%. The rhesus Rotavirus vaccine induces partial protection against heterotypic Rotavirus disease, but the level of protection achieved with the present vaccine dose in this age group appears to be insufficient for a general Rotavirus vaccination.", "A randomised, controlled trial of bovine rotavirus vaccine was undertaken in Gambian infants. Three doses were administered, from the age of ten weeks, concurrently with oral or killed polio vaccine. Prevaccination rotavirus neutralising antibody levels were high. 84/185 infants (45%) showed an increase in neutralising antibody titre after receiving rotavirus vaccine, compared with 20/91 (22%) unvaccinated infants. Clinical rotavirus infection was detected in 24/78 (31%) children in the rotavirus/oral polio group, 34/83 (41%) children in the placebo/oral polio group, and 23/92 (25%) children in the rotavirus/killed polio group, giving an overall vaccine efficacy of 33% (95% CI 4-53%). RIT 4237 did not appear to reduce the severity of clinical infections. Most cases (92%) were caused by rotaviruses with short RNA electropherotypes. Serological responses to rotavirus vaccination appeared unaffected by the concurrent administration of oral polio vaccine. Lower types 1 and 3 polio antibody levels were found in children who received oral polio and rotavirus vaccines but the differences were not statistically significant.", "Three phase I trials of the rhesus rotavirus (RRV)-based quadrivalent vaccine [composed of serotype 3 (RRV), and serotypes 1 (D x RRV), 2 (DS1 x RRV), and 4 (ST3 x RRV) human rotavirus x RRV reassortants] and the M37 (nursery strain) rotavirus vaccine candidates were conducted in an attempt to find a safe and optimally antigenic formulation. Infants 10-20 weeks old received, in trial I, 1) the quadrivalent vaccine as two separate bivalent doses (1 x 10(4) PFU each of D x RRV and RRV, followed 4 weeks later by 1 x 10(4) PFU each of DS1 x RRV and ST3 x RRV) or 2) placebo; in trial II, 1) one dose of quadrivalent vaccine (10(4) PFU of each component), or 2) two doses of quadrivalent vaccine, or 3) a 10(4) PFU dose of M37 vaccine, or 4) M37 vaccine followed by the quadrivalent vaccine, or 5) placebo; in trial III, 1) a dose of a higher-titered quadrivalent vaccine (10(5) PFU of each component), or 2) two doses of higher titered quadrivalent vaccine, or 3) a dose of higher titered M37 vaccine (10(5) PFU) or 4) two doses of M37 vaccine (10(5) PFU), or 5) M37 vaccine (10(5) PFU) followed by the higher titered quadrivalent vaccine, or 6) placebo. A mild, transient fever during the first week postvaccination was associated with the bivalent or quadrivalent vaccines but not with the M37 vaccine. Fourfold or greater serum IgA ELISA responses to rotavirus were observed in 48-92% of the infants receiving quadrivalent vaccine and in 32-50% of those receiving M37 vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)", "Rotaviruses are the principal known etiologic agents of severe diarrhea among infants and young children worldwide. Although a rhesus rotavirus-based quadrivalent vaccine is highly effective in preventing severe diarrhea in developed countries, in developing countries its efficacy has been less impressive. We thus conducted a catchment study in Venezuela to assess the efficacy of the vaccine against dehydrating diarrhea.\n In this randomized, double-blind, placebo-controlled trial, 2207 infants received three oral doses of the quadrivalent rotavirus vaccine (4x10(5) plaque-forming units per dose) or placebo at about two, three, and four months of age. During approximately 19 to 20 months of passive surveillance, episodes of gastroenteritis were evaluated at the hospital.\n The vaccine was safe, although 15 percent of the vaccinated infants had febrile episodes (rectal temperature, > or =38.1 degrees C) during the six days after the first dose, as compared with 7 percent of the controls (P<0.001). However, the vaccine gave 88 percent protection against severe diarrhea caused by rotavirus and 75 percent protection against dehydration, and produced a 70 percent reduction in hospital admissions. Overall, the efficacy of the vaccine against a first episode of rotavirus diarrhea was 48 percent. Horizontal transmission of vaccine virus was demonstrated in 15 percent of the vaccine recipients and 13 percent of the placebo recipients with rotavirus-positive diarrhea.\n In this study in a developing country, the quadrivalent rhesus rotavirus-based vaccine induced a high level of protection against severe diarrheal illness caused by rotavirus.", "To evaluate whether breastfeeding affected the immunogenicity and/or efficacy of candidate rhesus-human rotavirus reassortant vaccines.\n A total of 989 healthy infants between 4 and 26 weeks of age were enrolled into a 23-center, prospective, randomized, double-masked, controlled study of the safety, immunogenicity, and efficacy of three doses (4 x 10(4) plaque-forming units) of monovalent rhesus-human viral protein 7, or G, serotype 1 reassortant vaccine, (RRV-S1) or tetravalent vaccine (RRV-TV) consisting of rhesus-human reassortant G serotypes 1, 2, and 4, and the parent RRV G serotype 3. Vaccine efficacy was compared in the breastfed and nonbreastfed children as well as seroconversion rates and postvaccination geometric mean titers (GMTs) of neutralizing antibodies to human serotypes 1, 2, 3, and 4, RRV, and immunoglobulin A to RRV. GMTs in the two feeding groups were compared with and without adjustment for age at initiation of vaccination, prevaccination antibody titers, and the age and prevaccination titer interaction.\n The seroconversion rates to both vaccines by one or more assays were similar for the breastfed and the nonbreastfed groups (RRV-S1, 84% and 85%, respectively; RRV-TV, 94% and 93%, respectively). There were no significant differences in postvaccination GMTs to either vaccine, measured by any serologic assay, in the two feeding groups. The efficacy of the RRV-S1 vaccine was not significantly lower among the breastfed children than the nonbreastfed children (28% and 39%, respectively). RRV-TV, which is the vaccine being further evaluated for licensure, was equally protective in breastfed and nonbreastfed infants (50% and 51%, respectively). Logistic regression analysis, taking into account differences in age at vaccination and day 1 titer, revealed no evidence of differential vaccine efficacy in the two feeding groups for either vaccine.\n These results indicate that the RRV-TV vaccine, given as three doses of 4 x 10(4) plaque-forming units, induces similar seroresponses and protection in breastfed and nonbreastfed US children.", "A double-blind, randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of a rhesus rotavirus vaccine and RIT 4237, a bovine rotavirus vaccine, in a Navajo population. Infants aged 2-5 months were randomized to receive one dose of either 10(4) pfu of the rhesus rotavirus vaccine or 10(8) pfu of the RIT 4237 vaccine or placebo. Eleven (10.2%) of 108 infants in the rhesus vaccine group, 11 (10.4%) of 106 in the RIT 4237 group, and 9 (8.4%) of 107 in the placebo group experienced rotavirus diarrhea during the follow-up period of 17 months. Thus, in this population, neither vaccine was efficacious in preventing rotavirus diarrhea.", "Rotavirus is a leading cause of morbidity and mortality from dehydrating gastroenteritis in infants and young children worldwide. Virtually every child is infected by age 4 years, justifying universal childhood immunization when a safe and effective vaccine is available. We report the results of a multicenter, placebo-controlled field trial in the United States of monovalent serotype 1 and tetravalent (TV) rhesus-human reassortant rotavirus vaccines (RRVs).\n In this randomized, double-blind trial, 1278 healthy infants ages 5 to 25 weeks received three oral doses of RRV serotype 1, RRV-TV, or a placebo at approximately 2, 4, and 6 months of age. Vaccines contained 4 x 10(5) plaque-forming units of virus. Gastroenteritis episodes were monitored, and severity was graded throughout one rotavirus season. Two stool specimens per episode were tested for rotavirus.\n The incidence of reactions did not differ among treatment groups during the 5-day, postvaccination safety surveillance period for any of the three doses. Both vaccines significantly reduced the incidence of rotavirus gastroenteritis. Vaccination was most protective against serious rotavirus illness; RRV-TV prevented 49% of rotavirus episodes, 80% of very severe episodes, and 100% of dehydrating rotavirus illness. Reduction of rotavirus disease by RRV-TV resulted in significantly fewer total episodes of gastroenteritis of all causes and an 82% reduction in all cases of dehydrating diarrhea.\n RRV-TV is highly protective against very severe, dehydrating rotavirus gastroenteritis.", "Rotavirus is the most common cause of acute childhood gastroenteritis. Vaccination with live oral heterologous rotavirus vaccines may prevent rotavirus gastroenteritis. We assessed the efficacy of rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) against severe rotavirus gastroenteritis in Finnish children in a randomised placebo-controlled double-blind trial.\n Placebo or RRV-TV (titre 4x10(5) plaque-forming units) was given to infants at ages 2, 3, and 5 months. The children were followed up for one or two rotavirus epidemic seasons. The main outcome measure was protection against severe rotavirus gastroenteritis (score > or =11 on a 20-point severity scale). 2398 children were enrolled and received at least one dose of RRV-TV (n=1191) or placebo (n=1207). The primary efficacy analysis was based on children who received three doses of RRV-TV (n=1128) or placebo (n=1145).\n 256 episodes of rotavirus gastroenteritis occurred at any time during the study; 65 were among 1191 RRV-TV recipients, and 191 among 1207 placebo recipients (vaccine efficacy 66% [95% CI 55-74]; intention-to-treat analysis). 226 episodes were included in the primary efficacy analysis of fully vaccinated children (54 among 1128 RRV-TV recipients, 172 among 1145 placebo recipients; vaccine efficacy 68% [57-76]). 100 episodes were severe, eight in RRV-TV recipients and 92 in placebo recipients (vaccine efficacy 91% [82-96]).\n RRV-TV vaccine was highly effective against severe rotavirus gastroenteritis in young children. Incorporation of this vaccine into routine immunisation schedules of infants could reduce severe rotavirus gastroenteritis by 90% and severe gastroenteritis of all causes in young children by 60%.", "The safety and efficacy of a WC3 rotavirus vaccine was evaluated in a double-blind placebo-controlled trial involving 472 children in Bangui (Central African Republic). Each child received two doses of either placebo (235 children) or vaccine (237 children) at a 1-month interval, the first dose being given at 3 months of age. During the follow-up survey 9 months after the first dose, 117 rotavirus diarrhoeas were observed, 59 in the placebo group, 58 in the vaccinated group. The only positive effect of the vaccine was a significantly higher proportion of mild rotavirus diarrhoeal episodes in the vaccinated group than in the placebo group. Of the children in the vaccinated group, 60% had a positive immune response to WC3 rotavirus when tested by plaque reduction seroneutralization.", "Orally administered live rhesus monkey rotavirus vaccine (RRV, VP7 serotype 3) and human-rhesus reassortant rotavirus vaccine (DxRRV, VP7 serotype 1) were evaluated in a placebo-controlled field trial of 223 infants 2-4 months old. Both vaccines were mildly reactogenic but were generally well tolerated in the 10 days after vaccination. RRV and DxRRV were immunogenic, inducing serum antibody responses in 78% and 71% of the vaccines, respectively. Efficacy of RRV vaccine was 66% (P = .01) and of DxRRV vaccine 77% (P = .002) against rotavirus-associated illness in the first season after vaccination. Efficacy of RRV vaccine against rotavirus-associated illness over three rotavirus seasons was 51.2% (P = .045) and of DxRRV vaccine was 67.3% (P = .006). RRV vaccine provided heterotypic protection of 58.5% (P = .041) and DxRRV vaccine provided homotypic protection of 72.8% (P = .005) over three seasons against the predominant serotype 1 rotavirus.", "Between January and November 1989, we studied 174 infants aged 6 to 16 weeks in a randomized clinical trial to (1) determine the immunogenicity of a single dose of tetravalent rhesus rotavirus vaccine (RRV-TV) when administered with three different buffer regimens: no antacid buffer and small-volume (2.5-mL) and large-volume (30-mL) antacid buffer; and (2) examine the potential interference of RRV-TV on the immune response to oral polio vaccine. Immunogenicity of RRV-TV, measured as a fourfold rise in antibody titers to rotavirus, was similar in the groups receiving small- and large-dose buffer (45% and 49%, respectively) and significantly less in the group that received RRV-TV alone (23%). Administration of RRV-TV with oral polio vaccine did not significantly interfere with the neutralization response of oral polio vaccine poliovirus serotypes 1, 2, or 3, and overall, 29%, 87%, and 24% of the infants had a fourfold rise in titer to each serotype, respectively.", "Rotavirus vaccine could be administered most efficiently if it were incorporated into routine childhood immunizations and did not interfere with the immune response to the other vaccines, principally oral poliovirus vaccine (OPV). We conducted a placebo-controlled randomized trial giving oral rhesus rotavirus vaccine (RRV) (strain MMU 18006) alone and together with a child's first dose of OPV and diphtheria-tetanus toxoids-pertussis to examine the possible interaction of these vaccines. A total of 102 infants 2 to 3 months of age were randomized into 3 groups to receive (1) RRV with OPV, (2) placebo with OPV and (3) RRV 2 weeks after OPV. All infants were given diphtheria-tetanus toxoids-pertussis. Serum samples were collected at the time of OPV immunization and 3 to 5 weeks later. Three to 5 weeks after OPV immunization 60% of infants had a 4-fold rise in neutralization titer to at least one of the three poliovirus serotypes. The rate of antibody response to poliovirus did not differ by RRV groups but a lower rate was correlated with a shorter interval (3 vs. 5 weeks) between OPV vaccination and antibody measurement. Fifty-six percent of infants had a 4-fold rise of IgA and 62% had a 4-fold rise of neutralizing antibody to RRV; this rise did not differ according to time of OPV immunization. RRV was not associated with side effects and may be safely given with OPV to infants 2 to 3 months of age.", "A naturally attenuated, human neonatal strain, rotavirus vaccine candidate RV3, was tested in a limited phase II randomized double-blind controlled trial. Doses of 1 ml, containing placebo or 6.5 x 10(5) fluorescent cell forming units (fcfu) of virus in AGMK cells, were given at 3, 5 and 7 months of age. Limited replication in the small intestine is implied by the lack of virus excretion, and by the occurrence of an immune response in only 46% of the infants. However, those who developed an immune response were partially protected against rotavirus disease during the subsequent winter epidemic (protective efficacy 54%), supporting observations of protection induced by natural infection by this strain. Protection appeared to be heterotypic. Further trials are warranted, employing strategies to increase immunogenicity of this human rotavirus candidate vaccine.", "Orally administered rhesus rotavirus vaccine (RRV) was evaluated in a placebo-controlled study in 176 infants (ages 2 to 4 months). Eighty-eight infants received a dose of 10(4) plaque-forming units of the vaccine, and 88 received the placebo. RRV was well-tolerated but mildly reactogenic in the 10 days after vaccination. There were mild febrile reactions (greater than or equal to 38 degrees C rectally) in 40% of the vaccinees and in 16% of the placebo recipients (P = 0.001). More of the vaccinees had loose stools than did the placebo recipients (P less than 0.05). RRV was immunogenic and induced a 4-fold or greater rise in serum neutralizing antibody responses in 67% of the vaccinees; however, breast-fed infants were less likely to develop a seroresponse than infants who were not breast-fed. Despite the good immunogenicity of RRV the overall incidence of rotavirus-associated illnesses was similar between the vaccine and placebo recipients. The failure of RRV in Rochester may be related to the fact that the circulating rotaviruses were predominantly serotype 1 and RRV is a serotype 3 rotavirus. Because the serotypes of rotavirus that predominate may vary from year to year, a polyvalent preparation may be necessary to provide effective vaccination against rotaviruses.", "Fifty children, 3 months to 12 years of age, were given an experimental, orally administered, live attenuated rotavirus vaccine. Overall evidence of vaccine effectiveness as judged by vaccine virus shedding or a serologic response was seen in 82% of vaccinees. No clinical illness was seen in the rotavirus vaccinees when compared with 40 concurrently studied control children. No transmission to control children was observed even with close daily contact in a day-care setting. Young infants, generally less than 1 year of age, who had not previously experienced wild-type rotavirus infection shed significantly more vaccine virus. Limitation of virus shedding in those already exposed may be related to a prompt copro-IgA response which was significantly elevated by three days after vaccination. In summary, the development of this rotavirus vaccine, rhesus rotavirus-MMU-18006, is a promising step in the development of immunoprophylaxis against this major enteric pathogen.", "A double-blind, placebo-controlled trial of oral rhesus rotavirus vaccine at a dose of 10(4) plaque-forming units was performed in 114 young infants in Maryland. Significantly more vaccinees than controls had fever and vomiting during the week after vaccination, but these reactions were mild. Of the vaccinees, 83% had a fourfold or greater rise in neutralizing antibody to rhesus rotavirus vaccine and 69% shed vaccine virus. Seventeen percent of the vaccinees and 24% of controls had rotavirus-positive diarrhea during the 2 years of surveillance. Vaccine efficacy was therefore 29% (95% confidence limits, -31% to +66%). Stools from 12 of 13 episodes containing sufficient antigen to type were serotype 1. We conclude that rhesus rotavirus vaccine was infective, immunogenic, and probably acceptably attenuated but that this serotype 3 vaccine provided little heterotypic protection during serotype 1 outbreaks in the community.", "Candidate oral bovine rotavirus vaccine RIT 4237 or placebo was given to 252 Finnish infants at birth and at 7 months of age. No vaccine-associated reactions were observed. Primary rotavirus ELISA IgM responses were detected in 36% of the infants after the first vaccination; after the second dose 68% of the vaccinees were seropositive for rotavirus ELISA IgG antibody. The infants remained in clinical follow-up over two rotavirus epidemic seasons (total 28 months). Counted from child years in follow-up the overall vaccine protection rate was 43%. The clinical severity of rotavirus episodes was assessed using a numerical score 0-20. Vaccine protection rate for cases with a score greater than or equal to 7 was 57% and for cases with a score greater than or equal to 11 it was 89%. It is concluded that vaccination with a bovine rotavirus vaccine at birth and at 7 months of age, with the second dose given shortly before rotavirus epidemic season, protects infants against moderately severe and severe rotavirus diarrhoea in the first 2 years of life.", "Rhesus-human rotavirus reassortants incorporating the gene expressing the VP7 surface protein of human rotavirus serotypes 1 or 2, and the remaining ten genes from rhesus rotavirus (RRV) were evaluated as candidate oral vaccines in 2-4-month-old infants. A single dose of the serotype 1 reassortant vaccine which had a titre of 10(4) plaque-forming units (p.f.u.) induced a fourfold or greater antibody response in 81% of the recipients by a combination of ELISA and neutralization assays; 51% of the vaccinees developed a neutralizing antibody response to the vaccine strain. A single dose of the serotype 2 vaccine (10(4) p.f.u.) induced a seroresponse in all vaccinees by the combination of assays whereas 67% developed neutralizing antibodies to the vaccine strain. A combination of these two vaccines (0.5 x 10(4) p.f.u. of each) induced an overall seroresponse in 95% of the recipients but only 48% and 24% response in neutralizing antibodies to serotypes 1 and 2, respectively. A trivalent combination which included the two reassortants and RRV (0.33 x 10(4) p.f.u. of each strain) induced an overall response in 82% of the vaccinees, but only 30%, 20% and 65% developed a neutralizing antibody response to serotype 1, serotype 2, and RRV, respectively. Febrile reactions on days 2-5 after vaccination were seen in 23-45% of the infants receiving the various vaccines and combinations and in 5% of the placebo group. It is concluded that rhesus-human reassortant rotaviruses may be combined with each other and with RRV as a polyvalent vaccine, but the VP7-specific neutralizing antibody responses are likely to be lower after combined vaccination than following vaccination with a single reassortant rotavirus.", "Human rotavirus strain M37, isolated from an asymptomatic neonate, was evaluated as a live oral vaccine in a double-blinded, placebo-controlled trial involving 282 infants ages 2 to 6 months. Either 10(4) or 10(5) plaque-forming units (PFU) of the M37 vaccine were tested in 102 and 39 infants, respectively. The vaccine was well-tolerated; fever on Days 1 to 7 after vaccination was recorded in 12 and 18% of infants receiving 10(4) and 10(5) PFU of the M37 vaccine, respectively, compared with 6% of those receiving placebo; none of the vaccinees developed diarrhea. A rotavirus IgA enzyme-linked immunosorbent assay serum antibody response was detected in 47 and 76% of the infants receiving the 10(4) and 10(5) PFU vaccines, respectively. No clinical protection against rotavirus diarrhea was observed in the group vaccinated with the 10(4) PFU dose; the number of infants vaccinated with 10(5) PFU was too small for evaluation of vaccine efficacy. The M37 vaccine in a titer of 10(4) PFU was found to be inadequate; the 10(5) PFU dose was more immunogenic than the lower dose and warrants further study for clinical efficacy.", "The safety, immunogenicity, and efficacy of WC3 rotavirus vaccine was evaluated in a double-blind, placebo-controlled trial of healthy infants 2-12 months of age; 103 received one dose of vaccine and 103 received placebo. Vaccination appeared to be safe and induced an antibody response (WC3 neutralizing antibody) in 97% of vaccinees. Only 9 (9%) of these, however, produced antibody to human rotavirus serotypes; at least 7 of the 9 were naturally infected before vaccination. Neither the number of symptomatic episodes of rotavirus diarrhea (21 vs 25) nor the number of moderate to severe rotavirus illnesses (9 vs. 15) was significantly different in vaccine or placebo recipients, respectively, during a predominantly serotype 1 rotavirus season. A slight but significant decrease in mean symptom score was detected in vaccine recipients. Despite an overall lack of efficacy, protection could be correlated to previous rotavirus infection, high levels of WC3 neutralizing antibody, and preexisting (maternal) serotype 1 neutralizing antibody with a titer greater than or equal to 30.", "The objective of this study was to evaluate the efficacy of a live, attenuated bovine (strain WC3) x human (strain WI79, serotype G1) rotavirus reassortant (WI79-9) virus vaccine for prevention of symptomatic rotavirus gastroenteritis in infants. The study was a prospective, randomized, double-blind, placebo-controlled trial, conducted over a single rotavirus season in 325 infants who were 2 to 8 months old at enrollment. Subjects were randomized to receive either placebo or WI79-9 virus vaccine at 10(7.3) plaque-forming units in three oral doses each separated by 2 months. Subjects were followed for 7 days after each dose for occurrence of adverse events and during the subsequent winter for development of rotavirus gastroenteritis. Administration of WI79-9 virus vaccine was well-tolerated, and the rates of low grade fever after each dose were no higher in vaccine recipients (8 to 21%) than in placebo recipients (14 to 19%). The protective efficacy of the WI79-9 vaccine during a subsequent epidemic of predominantly serotype G1 rotavirus was 87.0% (95% confidence limits, 62.6 to 95.5%) against relatively severe rotavirus gastroenteritis (rotavirus gastroenteritis with a clinical severity score of > 8) and was 64.1% (95% confidence limits 35.9 to 79.9%) against all symptomatic rotavirus episodes. The WI79-9 vaccine was safe and effective in prevention of homotypic human rotavirus infection in infants. Further studies of reassortant vaccines based on the bovine WC3 rotavirus should be performed.", "We vaccinated 244 newborn infants orally with RIT 4237 bovine rotavirus vaccine or placebo and followed them serologically and clinically for 16 months. Initially 39 of the 119 (33%) vaccine recipients compared with 1 of the 120 placebo recipients seroconverted by enzyme-linked immunosorbent assay-immunoglobulin M. After the first winter rotavirus season, at 7 months of age 55% of the vaccinated infants and 37% of the unvaccinated infants were rotavirus-seropositive by enzyme-linked immunosorbent assay-immunoglobulin G (P less than 0.01, chi square test). At 12 months of age, after a low rotavirus prevalence season, 34% of the vaccinated children and 23% of the unvaccinated children remained seropositive. There were 14 confirmed episodes of rotavirus gastroenteritis in the vaccine group and 10 episodes in the placebo group during the first 16 months. However, only 1 of the episodes in the vaccine group was severe, 4 were moderately severe and 9 were mild, whereas 7 episodes in the placebo group were severe and 3 were moderately severe (P less than 0.001 between groups, Fisher's exact test). There was no clear correlation between vaccine-induced clinical protection and initial serologic response (enzyme-linked immunosorbent assay-immunoglobulin M) to vaccination, but during follow-up severe rotavirus gastroenteritis was more likely to occur in children with no serum rotavirus immunoglobulin G antibody at the time of infection. We conclude at the present stage that neonatal rotavirus vaccination with RIT 4237 vaccine gives no protection against rotavirus infection but appears to modify the severity of gastroenteritis.", "A single oral dose of bovine rotavirus vaccine RIT 4237 or placebo was given to 2 groups of 5-day-old infants, born in October 1984 (n = 244) and June 1985 (n = 245), who remained in follow-up for 2.8 and 2.0 years, respectively. The vaccine had no effect on the total number of detectable episodes of rotavirus diarrhoea: there were 22 cases in the vaccinees and 24 in the placebo recipients in the October group and 18 and 16 respectively in the June group. However, vaccination decreased significantly the clinical severity of rotavirus diarrhoea, as assessed by a numerical score 0-20; this vaccine effect was much greater in the infants born in October. The mean severity scores for vaccine and placebo recipients were 4.55 and 10.75 respectively in the October group (p less than 0.0001, t-test) and 8.2 and 11.6 respectively in the June group (p = 0.010, t-test). Vaccine-induced clinical protection against rotavirus diarrhoea did not correlate well with serological response after vaccination, but showed good correlation to the presence of rotavirus antibodies before the rotavirus epidemic season. It is concluded that bovine rotavirus vaccine is more efficacious when given immediately before the rotavirus epidemic season: the vaccine effect may be amplified by exposure to wild rotaviruses during the season.", "The safety and immunogenicity of an orally administered live human rotavirus vaccine candidate (89-12), attenuated by 33 passages in monkey kidney cells, were evaluated in placebo-controlled trials in adults, children and infants. This strain was selected because natural infections with 89-12-like rotaviruses provided 100% protection over two years. The initial evaluations in adults, seropositive children and nine infants indicated that the vaccine was safe. Two doses of vaccine (10(5) p.f.u. dose-1) or placebo were then given to 42 infants, aged from 6 to 26 weeks. No significant difference in side effects was seen. Seroconversion was demonstrated in 19 of 20 previously uninfected vaccine recipients, but > or = 4-fold rises in 89-12 neutralizing antibody titers were detected in only seven subjects. Intestinal IgA responses were detected in 15 subjects. This attenuated human rotavirus was safe and immunogenic and should be further evaluated as a vaccine candidate.", "The safety and protective efficacy of a serotype 1 reassortant of bovine rotavirus WC3, disignated strain WI79-9, was evaluated in a double-blind placebo-controlled trial. Rotavirus reassortant WI79-9 contains a gene segment 9 coding for the surface structural protein vp7 of a human serotype 1 rotavirus, with all other gene segments derived from WC3 rotavirus, which had previously been shown to be safe and immunogenic in infants. Infants 2-11 months of age were given two doses of vaccine (10(7.3) plaque-forming units/dose) or of placebo 28 days apart. Adverse reactions to the vaccine were not detected. The incidence of serum plaque reduction neutralization antibody responses to two doses of vaccine was serotype 6, 97%; serotype 3, 68%; and serotype 1, 22%. Active surveillance during the subsequent rotavirus season revealed 8 cases of rotavirus gastroenteritis in 39 placebo control infants and no cases in 38 WI79-9 vaccine recipients (protection = 100%, P = .003). Six cases of rotavirus gastroenteritis were caused by type 1 and two by type 3 virus. Although vaccination with WI79-9 affected only the incidence of rotavirus gastroenteritis, the vaccinated infants exhibited a significantly reduced incidence of total days of diarrhea, fever, and illness associated with gastroenteritis in general.", "90 Venezuelan infants aged 10-20 weeks were randomly allocated to four groups which received one of the following: the M37 vaccine (1 x 10(4) pfu [plaque-forming units]); quadrivalent rotavirus vaccine (1 x 10(4) pfu each of serotype 3 rhesus rotavirus [RRV] and human rotavirus-RRV reassortants of serotypes 1, 2, and 4); balanced quadrivalent vaccine consisting of 1 x 10(4) pfu of serotype 1 and 3 components but 5 x 10(4) pfu of serotype 2 and 4 components; or placebo. The frequencies of transient febrile responses in these four groups were 20%, 27%, 30%, and 9%. 50% of 22 infants tested who received M37 vaccine showed a serum rotavirus IgA antibody response, compared with 74% of the 23 quadrivalent and 86% of the 22 balanced-quadrivalent recipients. 64% of the M37 recipients showed a neutralising antibody response to M37; 27% showed such responses to human serotype 1 Wa strain and 27% to serotype 4 neonatal strain ST3. 17-39% of the quadrivalent recipients and 27-41% of the balanced-quadrivalent recipients showed neutralising antibody responses to serotypes 1-4. 70-73% of the quadrivalent and balanced quadrivalent groups also showed neutralising antibody responses to RRV.", "The safety, infectivity, and immunogenicity of two human-bovine reassortant rotavirus candidate vaccines were evaluated in adults, children, and infants. One of these, Wa x UK, contained a single human rotavirus gene from the Wa strain that encoded VP4 P1A specificity in a background of 10 bovine genes including the VP7 gene that encodes G6 specificity, whereas the other, Wa x (DS-1 x UK), possessed the human rotavirus VP4 gene from the Wa strain as well as the human VP7 gene from strain DS-1 that encoded G2 specificity. Each of these vaccines appeared to be well-tolerated and immunogenic in infants less than 6 months of age following a single oral dose, and therefore should be evaluated further as vaccine candidates.\n Copyright 2002 Wiley-Liss, Inc.", "We evaluated the reactogenicity and antigenicity of a quadrivalent rotavirus vaccine composed of serotype 3 rhesus rotavirus (RRV) and three single-gene-substitution reassortants of RRV and human strain D (D x RRV, serotype 1), DS1 (DS1 x RRV, serotype 2), or ST3 (ST3 x RRV, serotype 4) in a double-masked study with 302 infants in Caracas, Venezuela. Three doses of the quadrivalent vaccine composed of either 10(5) PFU (low titer) or 10(6) PFU (high titer) of each component were administered to 99 and 101 infants, respectively, at 4-week intervals starting at the second month of age; 102 infants received a placebo. Postvaccination reactions were monitored by home visits every other day during the week postvaccination. The vaccine was associated with the occurrence of mild, short-lived febrile episodes in 26 and 23% of the recipients after the first doses of high- or low-titer vaccine, respectively, in comparison with 13% of the infants receiving the placebo. Febrile reactions occurred less frequently in vaccinees after the second or third dose than after the initial dose. The vaccine was not significantly associated with diarrhea or any additional symptom or sign. Serum specimens obtained shortly before the first, 4 weeks after the first, and 4 weeks after the third dose of vaccine or placebo were tested by an immunoglobulin A enzyme-linked immunosorbent assay and by neutralization assays. Seroresponses occurred significantly more often after 3 doses than after a single dose of either vaccine. Immunoglobulin A responses were observed in 80 and 79% of the infants after 3 doses of high- or low-titer vaccine, respectively. Most of the infants tested developed a neutralization response to RRV after 3 doses of the high- (90%) or low-(88%) titer vaccine. Neutralization response rates to human rotavirus serotypes 1 to 4 after 3 doses were similar in both vaccine and 87 of 90 receiving the high-titer vaccine developed seroresponses, as detected by any of the assays employed. The study indicates that 3 doses of quadrivalent vaccine at a titer of 10(6) PFU of each component offered no advantage over the lower-titer preparation for use in efficacy trials.", "In a four cell trial, a single 10(4) plaque-forming unit dose of rhesus rotavirus (RRV) vaccine (serotype G3), a human rotavirus-rhesus rotavirus reassortant vaccine with serotype G1 specificity, a similar vaccine with serotype G2 specificity, or a placebo was administered with buffer orally at 2 months of age to 800 Peruvian infants. Only the RRV vaccine was associated with a febrile response (< 38 degrees C) that occurred in 9% of the infants on day 4 after vaccination. Diarrhea or other side-effects were not associated with administration of vaccine. Vaccine strains were shed by only 12-18% of the infants as determined by examination of a single stool specimen obtained on days 4 or 5 after vaccination. Fifty per cent of vaccines developed an IgA ELISA seroresponse; however, a serotype-specific seroresponse by plaque reduction neutralization was demonstrated in < 20% of the participants against each of the three candidate vaccine strains. Vaccine efficacy was evaluated by twice-weekly home surveillance for diarrheal diseases during 24 months post-immunization. Rotavirus diarrheal episodes were identified by ELISA. Only the RRV vaccine had a significant protective efficacy (29%, p = 0.03, chi-square test) against rotavirus diarrhea. Analysis of vaccine efficacy against rotavirus episodes of any severity in which no other enteropathogen was isolated showed a trend towards higher vaccine efficacy. In addition, a similar trend was observed in rotavirus-only episodes in which there was some degree of dehydration or when health services were utilized. Serotype G1 or G2 rotavirus strains were most prevalent during surveillance. Neither serotype G1 or serotype G2 vaccines were protective against serotype 1 or 2 rotavirus diarrhea, respectively. The serotype G2 vaccine was 84% protective against serotype 1 and 2 dehydrating rotavirus diarrhea in the small numbers of individuals evaluated. We conclude that one dose of 10(4) p.f.u. of the RRV, serotype G1, or serotype G2 rotavirus vaccine failed to induce either an adequate serotype-specific seroresponse or serotype-specific protection in children immunized at 2 months of age. Only the RRV vaccine induced a low level of protection against rotavirus diarrhea mainly of serotype G1 specificity. Future studies need to explore whether higher vaccine dose and/or more than one dose would increase the immunogenicity and efficacy of the rotavirus vaccine, especially in developing countries with a high level of baseline rotavirus antibodies.", "nan", "Rotavirus is the most common cause of severe gastroenteritis among children worldwide.\n To compare the safety, immunogenicity and shedding patterns of rhesus rotavirus (RRV)-tetravalent vaccine vs. placebo among infants in rural Bangladesh.\n A double blinded, placebo-controlled trial was conducted in which infants (n = 120) were randomly assigned to receive three doses of either vaccine or placebo administered at approximately 6, 10 and 14 weeks of age together with routine immunizations. Data on possible adverse effects of vaccinations were collected daily for 7 days after each dose. Stool samples were collected after each dose, and serum samples were obtained before the first and after the third vaccination.\n Fever (> or = 38 degrees C), as measured by study assistants, was noted more frequently among vaccinees (15%) than among placebo recipients (2%) during the 7 days after vaccination but was not reported more frequently by parents of vaccinees vs. placebo recipients. Overall 87% of vaccinees had an antibody response (measured by IgA or anti-RRV-neutralizing antibodies) after vaccination compared with 32% of placebo recipients. Rates of seroconversion were higher among subjects with lower levels of prevaccination antibodies and those who shed rotavirus after vaccination. Vaccine strain viruses were detected in stools from placebo vaccine recipients who had evidence of IgA seroconversion.\n In this population RRV-tetravalent vaccine was comparably immunogenic and safe as in trials conducted in developed countries, where this vaccine has been proved effective in preventing severe rotavirus diarrhea. These data support continued evaluation of rotavirus vaccines in developing countries.", "A tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine (4 x 10(4) plaque-forming units/dose) was evaluated for safety, immunogenicity and efficacy in a prospective, randomized, double-blind, placebo-controlled trial involving 540 Brazilian infants. Doses of vaccine or placebo were given at ages 1, 3 and 5 months. No significant differences were noted in the occurrence of diarrhoea or vomiting in vaccine and placebo recipients following each dose. Low-grade fever occurred on days 3-5 in 2-3% of vaccinees after the first dose, but not after the second or third doses of vaccine. An IgA antibody response to rhesus rotavirus (RRV) occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing antibody responses to individual serotypes did not exceed 20% when measured by fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose (vaccine or placebo) recipients during two years of follow-up, 36 of them among children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005) against any diarrhoea and 35% (P = 0.03) against any rotavirus diarrhoea. Protection during the first year of follow-up, when G serotype 1 rotavirus predominated, was 57% (P = 0.008), but fell to 12% in the second year. Similar results were obtained when analysis was restricted to episodes in which rotavirus was the only identified pathogen. There was a tendency for enhanced protection by vaccine against illness associated with an average of 6 or more stools per day. These results are sufficiently encouraging to warrant further studies of this vaccine in developing countries using a higher dosage in an attempt to improve its immunogenicity and efficacy.", "A randomised, double-blind, placebo-controlled trial was conducted to evaluate the ability of RIT 4237 live attenuated bovine rotavirus (subgroup 1) vaccine strain to protect against natural rotavirus infection in children. 178 infants aged 8 to 11 months received a single oral dose of RIT 4237 vaccine or placebo and were followed up serologically and clinically during a subgroup 2 rotavirus epidemic. No side-effects attributable to the vaccine were observed. During the 5 months' observation after vaccination 2 of the 86 vaccine recipients and 18 of 92 placebo recipients had rotavirus diarrhoea lasting more than 24 h (p less than 0.001). The vaccine-protection rate was thus 88%. The 2 children in the vaccine group with rotavirus diarrhoea were regarded as primary vaccine failures since they had no detectable serum antibody responses after vaccination. Vaccine prepared from RIT 4237 strain of attenuated bovine rotavirus thus seems to protect children against heterologous subgroup 2 rotavirus diarrhoea.", "To compare the safety and immunogenicity of two dosages of tetravalent rhesus rotavirus vaccine (RRV-TV) and the effect of age at dosing.\n A total of 195 infants were stratified by age into 2 groups, 6 to 12 weeks and 16 to 24 weeks, and randomly assigned to receive a single dose of placebo or RRV-TV containing either 4 x 10(5) or 4 x 10(6) plaque-forming units (pfu). Symptoms were recorded for 5 days after vaccination. Anti-rotavirus IgA and neutralizing antibody to human rotavirus serotypes G1 to G4 and RRV were measured in serum obtained pre- and postvaccination.\n Rates of fever > 38 degrees C (9%), diarrhea (6%) and vomiting (8%) were similar in all groups. IgA (69% vs. 49%, P = 0.02) and RRV (85% vs. 66%, P = 0.004) seroconversion rates were significantly higher in the 4 x 10(6) pfu vaccine group as were antibody titers to RRV (440.2 vs. 263.7, P = 0.04). Older infants demonstrated significantly higher seroconversion rates and antibody titers for IgA (71% vs. 52%, P = 0.03; and 110.6 vs. 54.8, P = 0.004) and RRV (92% vs. 66%, P = 0.05 and 498.3 vs. 205.6, P = 0.01) at either dose level than did the younger infants. There were no significant differences in seroconversion rates or antibody titers to human rotavirus types G1 to G4 between the two vaccination groups.\n RRV-TV at a dose of 4 x 10(6) pfu can be safely administered to infants 6 to 24 weeks of age. A single dose of 4 x 10(6) pfu of RRV-TV was significantly more immunogenic than a single dose of 4 x 10(5) pfu but did not improve responses to the human serotypes. Older vaccine recipients demonstrated significantly higher IgA and neutralizing antibody seroconversion rates and antibody titers than younger infants independent of dosage.", "nan", "Rhesus rotavirus oral vaccine strain MMU 18006 at a dose of 10(5) plaque-forming units (PFU), a 1:10 dilution of the original undiluted vaccine, is highly immunogenic in young children. Fevers have occurred, however, on Days 3 and 4 following vaccination. This study was conducted to determine whether febrile reactions could be eliminated and immunogenicity maintained by (1) giving smaller doses of vaccine or (2) vaccinating younger infants. Thirty-one children between 3 and 11 months of age received, in a randomized, double blind manner, either 10(4) PFU of vaccine virus, 10(3) PFU of vaccine virus or placebo. All recipients of the 10(4) PFU dose had a seroresponse; however, some degree of immunogenicity was lost with the smaller dose (10(3) PFU). Fevers were observed in recipients of both of the lowered doses of vaccine but the febrile reactions were related to the age of the vaccinee. No infant younger than 5 months of age experienced a temperature elevation, whereas the majority of children older than 5 months had fevers. Our data suggest that the lack of reaction in the younger infants correlates with the presence of prevaccination neutralizing antibody, presumably transplacentally acquired. We conclude that the rhesus rotavirus oral vaccine at a dose of 10(4) PFU is immunogenic and appears to be safe in young infants.", "A randomized, double-blind trial was performed to assess serological response and clinical protection for acute gastroenteritis due to rotavirus in 103 children aged 6 to 18 months, after a single dose of RIT 4237 live attenuated bovine rotavirus vaccine or placebo. Seroconversion, determined by enzyme-linked immunoabsorbent assay (ELISA), was significantly greater in initially seronegative vaccines compared with control group (p less than 0.0001); clinical protection rate was low in this study group and it is therefore concluded that seroconversion by itself is not sufficient to measure vaccine efficacy.", "Phase I studies of an oral quadrivalent rotavirus vaccine were conducted in 130 Venezuelan infants 10 to 20 weeks of age. The vaccine consists of a mixture of equal amounts of rhesus rotavirus (RRV) vaccine (serotype 3 [VP7]) and each of three human rotavirus-RRV reassortant strains: D x RRV (serotype 1 [VP7]), DS1 x RRV (serotype 2 [VP7]), and ST3 x RRV (serotype 4 [VP7]). Three different doses of the quadrivalent vaccine (0.25 x 10(4), 0.5 x 10(4), and 10(4) PFU of each component) were evaluated sequentially for safety and antigenicity in placebo-controlled, double-blind trials. Starting the day after vaccination, the infants were monitored by daily home visits for 7 days. Only minor reactions were observed during this period; these were limited to mild transient febrile episodes which began day 2 or 3 after vaccination and lasted 1 to 2 days in 15 to 30% of the infants. Serological studies demonstrated that 68 to 96% of the infants developed a rotavirus serum immunoglobulin A response following vaccination. However, when tested by plaque reduction neutralization assay against individual human rotavirus serotype 1, 2, 3, or 4, the response rates ranged from 4 to 23% with the low dose, 21 to 33% with the medium dose, and 32 to 58% with the high dose. Most (73 to 79%) infants developed neutralizing antibodies to RRV following administration of each dose schedule. Vaccine virus shedding was analyzed by utilizing tissue culture isolation of virus from stool. All of the infants who received the lower of medium dose and 89% of those fed the high dose shed one or more components of the vaccine. Analyses of rotavirus serotypes isolated from the stool of infants who received the 0.25 x 10(4) -PFU dose revealed that DS1 x RRV was the most commonly shed vaccine component, followed by RRV, D x RRV, and ST3 x RRV in that order.", "The efficacy of a rhesus rotavirus vaccine (MMU 18006, serotype 3) against infantile diarrhea was evaluated by active home surveillance of a group of 320 children 1-10 months of age in Caracas, Venezuela. During a 1 year period following oral administration of vaccine or placebo under a double-masked code, over 600 diarrheal episodes were detected. Etiologic studies revealed that heat-stable toxin (ST) producing enterotoxigenic E. coli (ETEC) was the most common diarrheal agent detected (34%) followed by enteropathogenic E. coli (EPEC, 10.9%), heat-labile toxin (LT) producing ETEC (7.6%), rotavirus (6.9%), Cryptosporidium (4.8%) and Campylobacter (1.3%). ST-producing ETEC were also recovered from over 20% of control stool specimens obtained during diarrhea-free periods, whereas EPEC, rotavirus, Cryptosporidium, and Campylobacter were rarely detected in such control specimens. Rotavirus was responsible for about one-half of the more severe cases of diarrhea. Twenty-two of 151 infants who received placebo (14.6%) and eight of 151 receiving a 10(4) PFU dose of vaccine (5.3%) had rotavirus diarrhea during the follow-up period for an efficacy level of 64% against any rotavirus diarrhea. However, vaccine efficacy reached 90% against the more severe cases of rotavirus diarrhea and was noticeably high in the 1-4 month age group. Serotypic analysis of the rotaviruses detected suggests that the resistance induced by the vaccine was type specific since significant protection was only evident against serotype 3 rotaviruses. A 10(3) PFU dose tested initially in 18 children did not appear to protect against rotavirus diarrhea.", "To assess safety and immunogenicity, 213 healthy infants aged 6 weeks to 4 months were randomized to receive a single dose of placebo, a 10(4) or 10(5) p.f.u. dose of rhesus rotavirus (RRV) serotype 3, human-RRV reassortant (VP-7 serotypes 1, 2 or 4) or a 10(4) or 10(5) p.f.u. dose of tetravalent rotavirus vaccine (containing equal parts of serotype 1, 2, 3 and 4 strains). The infants were fed ad libitum before and after vaccination; no buffer was used. For 7 days after vaccination, potential vaccine side effects were monitored, and no significant differences were noted for any symptom evaluated among the single serotype, tetravalent or placebo groups. Sera, obtained before and 28 days after vaccination, were measured for antibody to rotavirus by IgG, IgA and IgM enzyme-linked immunosorbent assay in all subjects, and by neutralizing antibody to the individual serotypes by plaque reduction in placebo and tetravalent vaccinees. The serological response rates for serotypes 1, 2, 3, 4 and the tetravalent vaccine were 25, 12, 19, 11 and 22%, respectively, at 10(4) p.f.u.; 47, 50, 35, 29 and 61%, respectively, at 10(5) p.f.u.; and 37% for placebo. The tetravalent vaccine was more immunogenic at 10(5) than at 10(4) p.f.u. (p = 0.04). Grouped together, the vaccines at 10(5) p.f.u. (single serotype and tetravalent) were more immunogenic than the vaccines at 10(4) p.f.u. (38 of 85 versus 17 of 94 seroresponders; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "Ninety-six healthy infants ages 2 to 5 months received rhesus rotavirus vaccine serotype 3 (RRV) as a single dose of 10(3), 10(4) or 10(5) plaque-forming units (pfu) in this double-blinded, placebo-controlled study. Half of the infants in each dose group were also randomized to receive either 30 ml of infant formula as buffer before vaccination or were vaccinated on an empty stomach. The incidence of fever, increased stool frequency and decreased activity level was consistently higher among infants who received RRV than those who received placebo. There was no consistent increase in incidence of symptoms as the dose of RRV was increased. Possible vaccine-related side effects were increased in older vaccinees and in those with higher pre-vaccination antibody titers. The seroconversion rate and pre to postvaccination antibody rise, evaluated by enzyme-linked immunosorbent assay and by plaque reduction neutralization, correlated well. The 10(5) and 10(4) pfu RRV dose produced significantly higher rates of seroconversion and higher antibody rises than did placebo (P less than 0.001 for 10(5) and P = 0.005 for 10(4]. The 10(3) pfu dose was no more immunogenic than placebo. In the 10(4) pfu dose group 73% of infants receiving formula as a \"buffer\" seroconverted compared with 36% of those not receiving formula; 63% of infants partially breast-fed or formula-fed seroconverted compared with 17% of those exclusively breast-fed. These differences in seroconversion rate were largely overcome by increasing the RRV dose to 10(5) pfu. Stool (copro IgA) antibody responses were examined; of six infants showing a copro IgA response only one had seroconverted based on enzyme-linked immunosorbent assay or plaque reduction neutralization. RRV was recovered by tissue culture more frequently from the stool in those infants who received RRV 10(5) and 10(4) pfu than among those receiving 10(3) pfu or placebo (P less than 0.001).", "The reactogenicity and antigenicity of the rhesus rotavirus vaccine, strain MMU18006, developed at the Laboratory of Infectious Diseases (National Institute of Allergy and Infectious Diseases, National Institutes of Health) were examined in a double blind, placebo-controlled study of 40 newborn infants in Caracas, Venezuela. The children were observed for the first few days after birth in the hospital nursery and by home visits for 10 days after vaccination to detect any adverse reactions. No reactions could be attributed to the vaccine. Serologic responses to the vaccine were evaluated in paired sera obtained at birth (cord blood) and 4 weeks after vaccination. Serologic responses to the vaccine were not observed by complement fixation, neutralization or a rhesus rotavirus VP7 epitope-specific competition assay. However, such responses were found in 9 of 14 tested infants by an immunoglobulin A-specific enzyme-linked immunosorbent assay. Seventeen of the 20 vaccinees also shed rhesus rotavirus vaccine in stool during the postvaccination period.", "nan", "To determine the safety and relative efficacy of two reassortant rhesus rotavirus vaccines over two rotavirus seasons.\n A prospective, double-masked, placebo-controlled trial.\n Twenty-three centers in the United States.\n A total of 1006 healthy infants between 4 and 26 weeks of age were enrolled, and 898 received three doses of vaccine or placebo.\n Reactogenicity was determined by comparing the incidence of fever, diarrhea, and/or vomiting for 5 days after each dose of vaccine. Rotavirus IgA and neutralizing antibody to rhesus rotavirus and four rotavirus serotypes were measured in a subset of subjects. Relative efficacy was determined by comparing the incidence of rotavirus gastroenteritis after three doses of vaccine or placebo over two rotavirus seasons.\n Adverse reactions were mild and limited to a small but significant increase in the incidence of fever after the first dose of tetravalent but not monovalent vaccine. The relative efficacy against rotavirus disease over the 2 years of observation was 40% (98.3% confidence interval, 7% to 62%) for the monovalent and 57% (98.3% confidence interval, 29% to 74%) for the tetravalent vaccine. In post hoc analyses, the relative efficacy against very severe rotavirus gastroenteritis was 73% and 82% for monovalent and tetravalent vaccine recipients, respectively. Also, a 67% and 78% reduction in medical visits for rotavirus gastroenteritis was observed. Both vaccines protected against disease caused by serotype 1 rotavirus, but only the tetravalent vaccine reduced the incidence of disease caused by non-serotype 1 rotavirus infection detected in the second season. It is unclear, however, whether this result represents serotype-specific protection or a difference in the duration of protection.\n Vaccination with both vaccines was safe and significantly reduced the incidence of rotavirus gastroenteritis, but only the tetravalent vaccine provided protection against disease caused by non-serotype 1 rotaviruses during the second year of follow-up.", "A randomized placebo-controlled double-blind field trial of RIT 4237 attenuated rotavirus vaccine in Lima, Peru, evaluated the protection against diarrheal illness by one, two, or three doses of vaccine. There were 391 children, 2-18 months old, studied for the occurrence of diarrhea during the 18 months after vaccination. Three doses of the vaccine provided 40% protection against any diarrheal illness associated with rotavirus alone but 58%-75%; protection against the more severe rotaviral illnesses. The vaccine appeared to be more efficacious when it was administered to children in the first year of life. Three doses provided up to 89% efficacy against more severe diseases due to serotype 1 rotavirus, and one dose also afforded significant protection. The protection was lower, even with three doses, against serotype 2 rotavirus. This vaccine trial has provided important insights on how such trials should be conducted and on the serotype-specificity of protection from rotavirus infection. Future vaccines should be able to protect against severe disease caused by all rotavirus serotypes and must work in developing countries where rotavirus is the most important cause of diarrheal mortality.", "To conduct a phase 1 safety and tolerability trial of an oral rotavirus vaccine candidate RV3 in healthy volunteers.\n Double blind placebo controlled trial of a single 1 mL oral dose (6.5 x 10(5) fluorescing focus units [FFU]/mL) in 10 healthy young men, 10 3-4 year old children and 10 3 month old infants with a 4 week surveillance period. The study was undertaken at a children's hospital and nearby community in Melbourne, Australia.\n All subjects successfully completed the trial. There were no significant side-effects attributable to the vaccine preparation in any age group. No shedding of vaccine virus was detected by enzyme immunoassay. There was evidence of an immune response in serum and/or gut secretions in two of five vaccinees in each age group.\n RV3 rotavirus vaccine appears to be safe and well tolerated. Evidence of immunogenicity in some subjects after a single dose encourages further trials to determine immunogenicity after three doses, after reduction of viral dose, and without prior administration of buffer.", "Rhesus-human rotavirus (RV) reassortant vaccine strains D x RRV or DS 1 x RRV with VP7 serotype 1 or 2 specificity were evaluated for safety, immunogenicity and protective efficacy in a double blind placebo-controlled three cell trial involving 359 infants ages 2 to 5 months. The titer of the D x RRV vaccine was 10(4) and that of the DS 1 x RRV vaccine was 10(5) plaque-forming units/1-ml dose. The vaccines were acceptably reactogenic, each inducing a transient febrile response in fewer than one-third of the vaccinees. Seroconversion by RV enzyme-linked immunosorbent assay IgA antibody was detected in 61 and 75% of the vaccinees receiving a single dose of the serotype 1 or 2 reassortant vaccine, respectively. Efficacy against RV diarrhea was evaluated in two successive epidemic seasons; RV serotype 1 was prevalent in both. Clinical efficacy was observed with both vaccines and was associated with seroconversion after vaccination; considering only such vaccinees both vaccines showed equal efficacy. The overall rates of protection for the two vaccines combined against clinical RV disease in children with seroconversion after vaccination were 92 and 59% in the first and second RV epidemic seasons, respectively. Protection against asymptomatic RV infection, as measured by serologic responses, was 59% in the first season and nil in the second season. It is concluded that each of the reassortant RV vaccines was effective in inducing protection against symptomatic RV disease associated with RV serotype 1.", "Live rotavirus vaccine candidates representing VP7 serotypes 1, 2, 3 or 4 derived by reassortment between bovine UK rotavirus and human rotavirus strains D, DS-1, P or ST3 were evaluated for safety and immunogenicity in adults, children and infants. Infection was defined by evidence of rotavirus shed in stools or a 4-fold or greater increase in serum rotavirus-specific IgA or IgG ELISA or plaque reduction neutralization antibody. A single oral dose (10(5.3) or 10(5.8) pfu) of reassortant virus was well tolerated and infected most infants: 10/20 (50%) by D x UK; 9/11 (82%) by DS-1 x UK; 8/10 (80%) by P x UK and 13/14 (93%) by ST3 x UK. All 14 infants given two doses of D x UK were infected. These findings demonstrating satisfactory levels of attenuation, safety, infectivity and immunogenicity of each reassortant in infants warrant additional studies of a candidate vaccine containing these four strains.", "In a double blind placebo-controlled study rotavirus vaccine RIT 4237 was offered to young infants after the fourth week of life. The vaccine was very well tolerated. Fifty-seven out of 100 vaccine recipients and 10 out of 103 placebo recipients developed rotavirus-IgM-antibodies during the 1 month follow-up period. During a 6 month follow-up, stool samples from 2 out of 12 vaccinees and from 5 out of 12 placebo recipients contained rotavirus.", "We compared the efficacy, safety, and immunogenicity of a rhesus rotavirus tetravalent vaccine (RRV-TV), a rhesus rotavirus monovalent (serotype 1) vaccine (RRV-S1), and placebo in healthy American Indian infants for two rotavirus seasons.\n Infants aged 6 to 24 weeks were enrolled in a randomized, double-blind efficacy study. Infants were orally administered RRV-TV (4 x 10(5) plaque-forming units per dose), RRV-S1 (4 x 10(5) plaque-forming units per dose), or placebo at 2, 4, and 6 months of age. Stools collected during episodes of gastroenteritis were tested for detection of rotavirus antigen. A total of 1185 infants received at least one dose of a study vaccine or placebo, and 1051 received all three doses according to the protocol.\n During the first year of surveillance, the estimates of vaccine efficacy (with 95% confidence interval) for preventing rotaviral gastroenteritis were 50% (26, 67) for RRV-TV and 29% (-1, 50) for RRV-S1. In this population only 6% of rotaviral gastroenteritis episodes among placebo recipients were associated with type G1 disease. For severe disease the estimates of vaccine efficacy were higher: 69% (29, 88) for RRV-TV and 48% (-4, 75) for RRV-S1.\n These data indicate that RRV-TV is moderately efficacious in preventing all episodes of gastroenteritis caused by rotavirus and is most efficacious against the severe disease characteristic of rotaviral illness.", "Heterologous live, oral rotavirus vaccines of rhesus monkey (RRV-1) and bovine (RIT 4237) origin were tested for immunogenicity, excretion of virus, and clinical reactions in six- to eight-month-old infants. Antibody response, indicating infection with the vaccine virus, was detected in 21 (88%) of 24 children receiving the RRV-1 vaccine and in 18 (75%) of 24 receiving the RIT 4237 vaccine. Excretion of virus in the stools within one week after vaccination was demonstrable in 84% of the RRV-1 and in 21% of the RIT 4237 vaccinees. RRV-1 vaccination was associated with a febrile response (over 38 C) that clustered on days 3 or 4 postvaccination in 64% of the recipient children. In addition, 20% of the RRV-1 vaccinees had watery stools on days 4 or 5. Fever on days 3 and 4 and loose stools were not seen in the RIT 4237 vaccinees. We concluded that in young children the RRV-1 (rhesus monkey) rotavirus vaccine is more immunogenic than the RIT 4237 (bovine) rotavirus vaccine, but vaccination with RRV-1 is associated with significant adverse reactions.", "In a randomized, double-blind, placebo-controlled trial, 331 infants aged 6 to 12 months received orally, at an interval of 1 month, either two doses of live attenuated bovine rotavirus vaccine strain RIT 4237 or equivalent placebo. The vaccinations were carried out during September to November, a non-rotavirus season; only three cases of rotavirus diarrhea occurred in the study group before the vaccinations were completed. During the epidemic season from December to May, 31 patients with clinically significant rotavirus diarrhea required therapy. Five of these were among the 168 vaccine recipients, and 26 among the 160 placebo recipients (P less than 0.001), giving a vaccine protection rate of 82%. The incidence of clinically significant diarrhea from all causes was reduced by 76% in the vaccinees. As determined by an enzyme immunoassay antibody test with homologous virus antigen, seroconversion after vaccination was obtained in 53% of the initially seronegative infants. Clinical protection correlated well with seroconversion, but the vaccinees who failed to seroconvert also had less rotavirus diarrhea than the placebo recipients, suggesting that immunity may be mediated by factors other than serum EIA antibody. Seventeen of the 23 rotavirus isolates in the epidemic season that were typed were of serotype 1, two were of serotype 2, and four were of serotype 3. The protection rates against clinically significant diarrhea were 72%, 100%, and 100% for serotypes 1, 2, and 3, respectively. We conclude that epidemic infantile winter diarrhea associated with human rotaviruses can be significantly reduced by vaccination with the live attenuated RIT 4237 bovine rotavirus vaccine before the epidemic season.", "To investigate the incorporation of oral rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine into a routine immunization programme, RRV-TV or oral placebo was coadministered with a pentavalent diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae b (Hib)-inactivated polio vaccine and hepatitis B vaccine following a 3-4-5-mo schedule in a double-blind trial involving 249 infants. Seroconversion rates after 3 doses of rotavirus vaccine were 80% for rotavirus immunoglobulin A (IgA) and 93% for RRV neutralizing antibodies. Rotavirus vaccine did not interfere with the immune responses to diphtheria, tetanus, pertussis, Hib, poliovirus 1, 2 and 3, or hepatitis B. Following the first, second and third doses of vaccine, fever >38 degrees C on the day of vaccination was seen in 31%, 24% and 24%, respectively, with no difference between RRV-TV- and placebo-vaccinated children. This fever was presumably due to the whole-cell pertussis vaccine. Those vaccinees who received concomitant RRV-TV vaccine had another peak of fever around d 4 after the first dose, when 25% of them had fever >38 degrees C and 3% >39 degrees C. It is concluded that RRV-TV rotavirus vaccine can be given concurrently with other childhood immunizations following a 3-4-5-mo vaccination schedule. However, febrile reactions to RRV-TV rotavirus vaccine are common when the first dose is given at the age of 3 mo." ]

[ "18653121", "12823643", "12042457", "12967058", "16895884", "16359741", "17600848" ]

[ "Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits.", "Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia.", "Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages.", "Folic acid supplementation in dementia: a preliminary report.", "Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial.", "Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects.", "A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease." ]

[ "The relevance of low folate levels as determinants of cognitive deficits and the usefulness of folate supplementation in the treatment of cognitive deficits was reviewed from the literature. Over 40 papers and book chapters published in English, French, German, Italian and Spanish were examined. This represents those papers published in the international literature in the last 10 years which were identified by various key words including folate, cognition and aging (or ageing). Among these papers, only 13 articles specifically addressed issues relevant to the criteria adopted for this review. The remaining papers were principally concerned with depression and or with other pathologies of the aged associated with folate deficiency. Although the specific role of low folate levels in the physiopathology of dementia is still under debate, a growing consensus is emerging in the literature where low folate as well as cobalamin levels in aged patients with cognitive deficits are being considered as a sign of functional problems in the absorption and utilization of vitamins, and not merely as a sign of bad eating habits. In studies where folate compounds were evaluated for treatment effects, the results of a majority of investigations indicated that folate treatment was effective in lessening cognitive deficits. Treatment efficacy, however, has not yet been sufficiently demonstrated by these results because there were no controlled studies and the methodology was heterogeneous for the evaluation of cognitive characteristics. An ad hoc double-blind, controlled versus placebo pilot study was undertaken to evaluate the efficacy of folic acid in 30 aged patients with abnormal cognitive decline and folate level below 3 ng/ml to better understand the value of this type of intervention. Our results from this preliminary study demonstrated that patients treated with folic acid for 60 days showed a significant improvement on both memory and attention efficiency when compared with a placebo group. The intensity of memory improvement was positively correlated with initial severity of folate deficiency. On the contrary, the severity of initial cognitive decline was unrelated to the degree of folate deficiency.", "To examine the association of cognitive impairment with platelet activation and reactive oxygen species and total homocysteine levels; and to assess the biochemical efficacy of treatment with aspirin and vitamin supplements in people at high risk of dementia.\n People with dementia or mild cognitive impairment.\n In a 2 x 2 x 2 factorial design trial, 149 people at high-risk of dementia were randomized to receive either low-dose aspirin (81 mg) or placebo; and folic acid (2 mg) plus vitamin B12 (1 mg) or placebo; and vitamins E (500 mg) plus C (200 mg) or placebo. Participants were seen twice before and once after 12 weeks of treatment.\n At each visit, participants had their cognitive function assessed and had blood collected for homocysteine, folate and vitamin B12 determination and urine collected for markers of platelet activation (11-dehydro-thromboxane B2) and reactive oxygen species (8-epi-PGF2 alpha).\n Prior to treatment, cognitive function was inversely related with homocysteine and with urinary thromboxane and isoprostane, and these associations were independent of age. Aspirin was associated with a median reduction in 11-dehydrothromboxane B2 of 73% (P < 0.001). B-vitamins lowered plasma homocysteine concentration by 30% (P < 0.0001) and antioxidant vitamins lowered isoprostane excretion by 26% (P < 0.1). No effect of treatment on cognitive function was detected.\n Aspirin and B-vitamins were effective in reducing biochemical factors associated with cognitive impairment in people at risk of dementia. Large-scale trials are now required to assess the relevance of aspirin and B-vitamins for the maintenance of cognitive function in people at risk of dementia.", "Based on research demonstrating associations between folate, B-12 and B-6 vitamins and cognition and mood, we investigated the effects of short-term supplementation in 211 healthy younger, middle-aged and older women who took either 750 microg of folate, 15 microg of vitamin B-12, 75 mg of vitamin B-6 or a placebo daily for 35 d. In addition, we examined associations between dietary intake of these vitamins and cognition and mood. Usual dietary intake status was estimated using a retrospective, self-report, quantified food frequency questionnaire. Participants completed alternate forms of standardized tests of cognitive processing resources, memory, executive function, verbal ability and self-report mood measures before and after supplementation. Supplementation had a significant positive effect on some measures of memory performance only, and no effect on mood. Dietary intake status was associated with speed of processing, recall and recognition and verbal ability.", "Recent work on high plasma homocysteine levels in patients at risk for developing Alzheimer's disease has led to the hypothesis that folic acid supplementation might reduce risk in such patients. The authors report on the effects of folic acid 10 mg/day versus placebo on 11 patients (only 7 completers) with dementia and low-normal folic acid levels. This is the first study evaluating folic acid or placebo in patients with dementia. Subjects had low-normal baseline folic acid levels. The magnitude of change between baseline and second testing was not statistically significant between the 2 groups. However, there was a trend for the folate group to perform worse on two specific cognitive measures, suggesting a possible trend toward worsening of some cognitive abilities after the folic acid. The folic acid in very high doses was well tolerated. Larger studies are necessary before empirically administering folic acid to patients already suffering from dementia.", "Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive.\n The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged >/=70 y with mild vitamin B-12 deficiency.\n In a double-blind, placebo-controlled trial, 195 subjects were randomly assigned to receive 1000 microg vitamin B-12, 1000 microg vitamin B-12 + 400 microg folic acid, or placebo for 24 wk. Vitamin B-12 status was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of treatment. Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention, construction, sensomotor speed, memory, and executive function.\n Vitamin B-12 status did not change significantly after treatment in the placebo group; however, oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36%. Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains.\n Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function.", "Cognitive impairment is associated with increased blood concentrations of homocysteine and high blood viscosity. Previous studies have shown that vitamin B supplementation reduces homocysteine and enhances cognitive function in patients with mild dementia and low serum folic acid. However, whether folic acid enhances cognitive function in elderly subjects without dementia and normal serum folic acid is unknown. Twenty-four healthy elderly subjects (age 73.0+/-5.6 years, mean+/-S.D.) with normal serum folic acid (6.3+/-2.4 microg/l) and Mini Mental State Examination (MMSE) >27/30 were randomized to 4-week treatment with folic acid 5mg/day or placebo in a randomized, placebo-controlled, parallel-group study. Continuous Attention Test (CAT), Four-Choice Reaction Time (FCRT), Digit-Symbol Substitution (DSS), Scanning Memory Sets (SMS), and blood viscosity for different shear rates were measured before and after treatment. Folic acid supplementation induced a significant increase in serum folic acid levels (+13.8 versus +1.6 microg/l, p<0.001) and fall in homocysteine levels (-1.91 versus -0.41 micromol/l, p=0.05) compared to placebo. However, there was no significant change in CAT, FCRT, DSS, SMS, and blood viscosity between the two groups. Short-term folic acid supplementation does not enhance psychomotor performance or reduce blood viscosity in healthy elderly subjects with normal serum folic acid levels and preserved cognitive function.", "(1) to assess the effect of 1 mg folic acid supplementation of cholinesterase inhibitors (ChI) in a 6 month double-blind placebo-controlled study of patients with Alzheimer's Disease (AD) and (2) to assess whether outcome measures were affected by changes in homocysteine levels.\n Fifty-seven consecutive outpatients with probable AD were treated concurrently with a ChI and either folic acid or placebo. None had conditions or medication known to interfere with folate metabolism. Fasting folate and homocysteine levels were measured prior to commencing ChI and 6 months later. Response was categorised using criteria of the National Institute of Clinical Excellence (NICE).\n Twelve males and 29 females completed treatment (mean age 76.27 SD 6.23 years, Mini-Mental State Examination (MMSE) 23.49 SD 3.53, baseline homocysteine 18.39 SD 4.62 micromoles per litre). 23 received folic acid and 18 placebo. There were no significant baseline differences or use of individual ChI between the two arms. After 6 months a significant difference was seen in the change from baseline in combined Instrumental Activities of Daily Living and Social Behaviour scores between arms (folate+1.50 (SD 5.32) vs placebo -2.29 (SD 6.16) (p=0.03) but not change in MMSE scores. Sixteen of 23 subjects receiving folic acid and 7/18 placebo subjects were classified as NICE responders (p=0.05).\n This pilot double blind study suggests that response to ChI in patients with AD may be improved by the use of folic acid. The relationship between any change in homocysteine levels and response to treatment is discussed.\n Copyright (c) 2007 John Wiley & Sons, Ltd." ]

[ "19739491", "12242586", "21342352", "11533340", "21888510", "17158417", "11328958", "11335744", "14599040", "1575558", "15493734" ]

[ "[Quality of post-discharge growth in small for gestational age preterm infants: an explorative study].", "Body composition in preterm infants fed standard term or enriched formula after hospital discharge.", "Preterm infants fed nutrient-enriched formula until 6 months show improved growth and development.", "Randomized trial of nutrient-enriched formula versus standard formula for postdischarge preterm infants.", "Small for gestational age preterm infants: nutritional strategies and quality of growth after discharge.", "Posthospital discharge feeding for preterm infants: effects of standard compared with enriched milk formula on growth, bone mass, and body composition.", "Feeding preterm infants after hospital discharge: growth and development at 18 months of age.", "Growth of preterm infants fed nutrient-enriched or term formula after hospital discharge.", "Post-discharge nutrition of the very low-birthweight infant: interim results of the multicentric GAMMA study.", "Randomised trial of nutrition for preterm infants after discharge.", "Feeding with premature or infant formula in premature infants after discharge: comparison of growth and nutrition status." ]

[ "The Preterm newborns, especially if born small for gestational age (SGA), appear to be at risk for developing post-natal growth failure and an altered body composition. Nutrition-related growth during a critical window in infancy may affect the development of metabolic syndrome in adult life. Aim of the present study was to test the hypothesis that the post-discharge period is critical for programming the catch up growth and the later development of metabolic syndrome in small for gestational-age infants fed either standard or enriched formula.\n A clinic randomized explorative study was conducted. Twenty-seven preterm SGA infants (gestational age < or = 33 weeks; birth weight < or = 1500 g) underwent assessment of growth and body composition by means of an air displacement system at 36 weeks, 15 days and 1 months adjusted age. SGA infants were randomized to receive standard formula (Kcal: 67/100 ml, proteins: 1,4 g/100 ml) or enriched formula (Kcal: 75/100 ml, proteins: 2 g/100 ml) after discharge.\n No differences in weight, fat mass, length and head circumference were found in SGA infants fed standard formula as compared to those fed enriched formula at 15 day or 1 months adjusted age.\n This explorative study suggests that in SGA infants growth, both in terms of quantity and quality, is not influenced by different nutritional management during the early post-discharge period.", "Most preterm infants are still preterm and have a low birth weight when they are discharged from the hospital. An important issue is whether the long-term consequences of early growth restriction can be diminished by nutritional intervention in preterm infants after discharge from the hospital.\n To evaluate differences in growth and in weight gain composition of preterm infants fed standard term formula (SF) or enriched formula (PDF) after discharge from hospital during the first 2 months of life.\n Thirty-three healthy preterm infants, birth weight < 1750 g at gestational age < 35 weeks, were randomised to SF or PDF at the time of discharge from hospital. Anthropometric variables were studied longitudinally and body composition was measured using dual energy x-ray absorptiometry (DEXA) twice, before hospital discharge and two months later. Weight gain composition was calculated as the difference between the two determinations.\n Seventeen infants were fed SF and 16 PDF. Anthropometric variables and whole body composition were similar at birth, at the start of the nutritional study (mean age 45 days), and at the end of the study 2 months later. Over the whole study period, weight gain and weight gain composition were similar in the two groups. Sex did not appear to influence weight gain and weight gain composition. In infants with growth restriction at discharge there was a significant reduction of weight gain, fat mass gain, and bone mineral content deposition independently of the formula provided.\n There is no immediate effect on preterm infants of a nutrient enriched formula compared with a standard formula on growth, weight gain, or weight gain composition.", "The purpose of the present study was to determine the effect of feeding nutrient-enriched preterm formula to preterm infants until 6 months' corrected age (CA) on growth and development in the first 18 months of life.\n Very low-birthweight preterm infants were fed preterm formula until term (40 weeks CA). Infants were then assigned to one of three groups and were fed term formula until 6 months' CA (group 1, n= 29); preterm formula to 3 months' CA and then term formula to 6 months' CA (group 2, n= 30); or preterm formula until 6 months' CA (group 3, n= 31). Anthropometry was performed at term, 3, 6, 9, 12, 15, and at s18 months' CA. Mental and psychomotor development were assessed using the Bayley Scales of Infant Development II at 18 months' CA.\n Although body weight, length, head circumference and z score for CA at term in group 3 were significantly lower than those of groups 1 and 2, growth rates of these parameters were significantly higher in group 3 up to 18 months CA', as compared to groups 1 and 2. The mental developmental index and psychomotor developmental index of the Bayley test were not significantly different between the three groups.\n Very low-birthweight preterm infants fed nutrient-enriched preterm formula until 6 months' CA demonstrated significantly improved growth rates for bodyweight, length and head circumference, and comparable mental and psychomotor development throughout the first 18 months of life.\n © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.", "Preterm infants are frequently discharged from the hospital growth retarded and show reduced growth throughout childhood. In a large efficacy and safety trial, we tested the hypothesis that nutritional intervention in the first 9 months postterm would reverse postdischarge growth deficits and improve neurodevelopment without adverse safety outcomes.\n Two hundred eighty-four infants (mean gestation: 30.9 weeks) were studied; 229 were randomly assigned a protein, energy, mineral, and micronutrient-enriched postdischarge formula (PDF; N = 113) or standard term formula (TF; N = 116) from discharge (mean 36.5 weeks' postmenstrual age). A reference group (N = 65) was breastfed until at least 6 weeks' postterm. Outcome measures. Anthropometry was performed at 6 weeks and 3, 6, 9, and 18 months. Development was measured at 9 months (Knobloch, Passamanick, and Sherrard's developmental screening inventory) and 18 months (Bayley Scales of Infant Development II; primary outcome) postterm.\n At 9 months, compared with the TF group, those fed PDF were heavier (difference 370 g; 95% confidence interval [CI]: 84-660) and longer (difference 1.1 cm; 95% CI: 0.3-1.9); the difference in length persisted at 18 months (difference 0.82 cm; 95% CI: -0.04-1.7). There was no effect on head circumference. The effect of diet was greatest in males; at 9 months length deficit with TF was 1.5cm (95% CI: 0.3-2.7), and this remained at 18 months (1.5cm [95% CI: 0.3-2.7]). There was no significant difference in developmental scores at 9 or 18 months, although PDF infants had a 2.8 (-1.3-6.8) point advantage in Bayley motor score scales. At 6 weeks' postterm, exclusively breastfed infants were already 513 g (95% CI: 310-715) lighter and 1.6cm (95% CI: 0.8-2.3) shorter than the PDF group, and they remained smaller up to 9 months' postterm.\n 1) Improving postdischarge nutrition in the first 9 months may \"reset\" subsequent growth-at least until 18 months for body length. We intend to follow-up the children at older ages. The observed efficacy of PDF was not associated with adverse safety outcomes. 2) We cannot reject the hypothesis that postdischarge nutrition benefits motor development and this requires additional study. 3) Our data raise the possibility that breastfed postdischarge preterm infants may require nutritional supplementation, currently under investigation.", "Infants born preterm are at high risk for poor growth achievement. Small for gestational age (SGA (birth weight below the 10th percentile) preterm infants are even more prone to develop postnatal growth retardation in the early neonatal period, as they do not have a large storage of protein/energy. Both SGA and appropriate for gestational age (AGA: birth weight between the 10th and 90th percentiles) infants show persistent postnatal growth failure after discharge. Although the available data clearly demonstrate that preterm infants, especially if born SGA, exhibit postnatal growth retardation at the time of hospital discharge, the importance of the nutritional post discharge management has not been sufficiently taken into account. We have recently conducted a randomized controlled trial to assess whether infants born SGA may benefit from an enriched post discharge formula. This study suggests that the growth pattern in SGA preterm infants is not affected by the consumption of an enriched post discharge formula. The ponderal and linear growth of these infants does not accelerate to achieve early catch up growth. However, as far as the quality of growth is concerned, the fat mass accretion after term decelerates, so that an increase of fat free mass accretion takes place. Future research effort should be directed toward longer follow up and personalized nutrition management.", "Despite the theoretical benefits of nutrient-enriched formula given to preterm infants after hospital discharge, its role in reversing growth deficits after hospital discharge remains poorly defined.\n The aim was to determine the effect of different formulas on the growth, bone mass, and body composition of preterm infants after hospital discharge.\n This was a randomized, double blind comparison of a nutrient-enriched formula (EF) and a formula for term infants (TF) given for 1 y after hospital discharge. Compared with the TF, the EF had a higher energy density and higher contents of protein, calcium, and phosphorus (by 10%, 21%, 44%, and 11%, respectively) and higher contents of almost all other nutrients (by >or=10%).\n Birth weights of the infants were 630-1620 g (median: 1250 g) and gestational ages were 24-34 wk (median: 29 wk). TF resulted in significantly greater weight, length, head circumference measurements, and their respective z scores on the basis of age- and sex-specific norms. At the end of the study, the mean z scores for the corrected age of infants in the TF group were -0.37 for weight, 0.001 for length, and 0.50 for head circumference. The TF group also had significantly greater dual-energy X-ray absorptiometry measured bone and lean and fat mass than did the EF group (P < 0.05 for all comparisons).\n The use of EF for preterm infants after hospital discharge shows no advantage over TF in growth, bone mineralization, and body composition. More studies are needed to determine the optimal postdischarge nutrition support for preterm infants.", "We have shown that preterm infants fed a preterm formula grow better than those fed a standard term infant formula after hospital discharge. The purpose of this follow-up study was to determine whether improved early growth was associated with later growth and development. Preterm infants (< or =1750 g birth weight, < or =34 wk gestation) were randomized to be fed either a preterm infant formula (discharge to 6 mo corrected age), or a term formula (discharge to 6 mo), or the preterm (discharge to term) and the term formula (term to 6 mo). Anthropometry was performed at 12 wk and 6, 12, and 18 mo. Mental and psychomotor development were assessed using the Bayley Scales of Infant Development II at 18 mo. Differences in growth observed at 12 wk were maintained at 18 mo. At 18 mo, boys fed the preterm formula were 1.0 kg heavier, 2 cm longer, and had a 1.0 cm greater occipitofrontal circumference than boys fed the term formula. Boys fed the preterm formula were also 600 g heavier and 2 cm longer than girls fed the preterm formula. However, no differences were noted in MDI or PDI between boys fed the preterm formula and boys fed the term formula or between the boys fed preterm formula and girls fed the preterm formula. Overall, boys had significantly lower MDI than girls (mean difference, 6.0; p < 0.01), primarily reflecting lower scores in boys fed the term formula. Thus, early diet has long-term effects on growth but not development at 18 mo of age. Sex remains an important confounding variable when assessing growth and developmental outcome in these high-risk infants.", "At hospital discharge, preterm infants may have low body stores of nutrients, deficient bone mineralization, and an accumulated energy deficit. This double-blind, randomized study evaluated the growth of premature infants with birth weights <1800 g who were fed a 22 kcal/fl oz nutrient-enriched postdischarge formula (PDF) or a 20 kcal/fl oz term-infant formula (TF) from hospital discharge to 12 months' corrected age (CA).\n Infants were randomized to PDF or TF a few days before hospital discharge with stratification by gender and birth weight (<1250 g or >/=1250 g). The formulas were fed to 12 months' CA. Growth was evaluated using analysis of variance controlling for site, feeding, gender, and birth weight group. Interaction effects were also assessed. Secondary analyses included a repeated measures analysis and growth modeling.\n One hundred twenty-five infants were randomized; 74 completed to 6 months' CA and 53 to 12 months' CA. PDF-fed infants weighed more than TF-fed infants at 1 and 2 months' CA, gained more weight from study day 1 to 1 and 2 months' CA, and were longer at 3 months' CA. There were significant interactions between feeding and birth weight group-among infants with birth weights <1250 g, those fed PDF weighed more at 6 months' CA, were longer at 6 months' CA, had larger head circumferences at term 1, 3, 6, and 12 months' CA, and gained more in head circumference from study day 1 to term and to 1 month CA. The repeated measures and growth modeling analyses confirmed the analysis of variance results. The PDF formula seemed to be of particular benefit for the growth of male infants. Infants fed the PDF consumed less formula and had higher protein intakes at several time points. Energy intakes, however, were not different.\n Growth was improved in preterm infants fed a nutrient-enriched postdischarge formula after hospital discharge to 12 months' CA. Beneficial effects were most evident among infants with birth weights <1250 g, particularly for head circumference measurements.", "This report presents the interim results up to 12 mo corrected age (c.a.) of a multicentric, prospective, controlled study on very low-birthweight infants, randomized at 40 wk post-conception in two different groups of formula feeding: 80 Kcal/dL (group A) vs 70 Kcal/dL (group B) up to 55 wk of postconceptional age. Subsequently, all the babies were fed with a follow-on formula, with the introduction of solid foods at 6 mo c.a. Weight, length, head circumference and neurological conditions with psychomotor development (evaluated by the Griffiths' Developmental Scale) were measured at regular intervals and all of these parameters were satisfactory in both groups. For growth, in group A there was a greater increase in weight in boys at 55 wk and at 6 mo c.a., and small for gestational age (SGA) babies had a greater increase in length at 1 y of age, while head circumference caught up on growth from week 40 to week 55. Measured by the Griffiths' Developmental Scale, the SGA group fed 80 Kcal/dL had a better score at 6 mo; similarly boys fed 80 Kcal/dL had a better score at 6 and at 9 mo.\n Nutrition of very low birthweight infants post-discharge could have an influence on physical growth and on neurodevelopmental outcome. This interim report needs to be confirmed at the end of the study.", "In a randomised double blind trial, the effect on growth and clinical status of a nutrient enriched 'post-discharge' milk formula versus a standard term formula, was compared in 32 exclusively bottle fed preterm infants. The formulas were used as the sole milk intake up to a postnatal age of 9 months. Significant increases in linear growth and weight gain were observed in the infants who received the enriched diet. There were no differences in vomiting, posseting, or bowel habit between the groups. Formula volumes ingested were similar between diet groups, indicating that the difference in formula composition did not affect the infants' regulation of intake. These preliminary data suggest that there is a role for specially designed formulas for preterm infants after discharge from hospital.", "We designed this prospective randomized controlled study to evaluate the effects of premature and standard term formula on growth, nutrient intake and biochemical response in premature infants from hospital discharge to 6 months of corrected age. Premature infants with a gestational age of < or =35 weeks and a birth weight < or =1850 gm were assigned to receive premature infant formula (n = 19) or a standard term infant formula (n = 15). No differences were found between the two groups in weight, length, or head circumference at baseline or on follow-up. Infants fed premature formula had higher blood urea nitrogen and phosphorus at 3 months of corrected age. Those on the premature formula also had higher energy intake at 1 month of corrected age. We suggest that premature infants, especially very low birth weight infants, fed preterm infant formula after discharge until 6 months of corrected age tolerate the formula well and may benefit over those standard term formula." ]

[ "18827129", "11084187", "22375972", "15985339", "17888856" ]

[ "Nicotine gum for pregnant smokers: a randomized controlled trial.", "Nicotine patches for pregnant smokers: a randomized controlled study.", "A randomized trial of nicotine-replacement therapy patches in pregnancy.", "A randomised-controlled pilot study using nicotine patches with pregnant women.", "Nicotine replacement and behavioral therapy for smoking cessation in pregnancy." ]

[ "To estimate the safety and efficacy of treatment with 2-mg nicotine gum for smoking cessation during pregnancy.\n Pregnant women who smoked daily received individualized behavioral counseling and random assignment to a 6-week treatment with 2-mg nicotine gum or placebo followed by a 6-week taper period. Women who did not quit smoking were instructed to reduce the number of cigarettes smoked by substituting with gum. Measures of tobacco exposure were obtained throughout the study.\n Participants in the nicotine (n = 100) and placebo (n = 94) groups were comparable in age, race/ethnicity, and smoking history. Biochemically validated smoking-cessation rates were not significantly higher with nicotine gum compared with placebo (after 6 weeks of treatment: 13% compared with 9.6%, P=.45; at 32-34 weeks of gestation: 18% compared with 14.9%, P=.56). Using a completer analysis, nicotine gum significantly reduced the number of cigarettes smoked per day (nicotine gum: -5.7 [standard deviation (SD)=6.0]; placebo: -3.5 [SD=5.7], P=.035), and cotinine concentration (nicotine gum: -249 ng/mL [SD=397]; placebo: -112 ng/mL [SD=333]; P=.04). Birth weights were significantly greater with nicotine gum compared with placebo (3,287 g [SD=566] and 2,950 g [SD=653], respectively, P<.001). Gestational age was also greater with nicotine-replacement therapy than with placebo (38.9 weeks [SD=1.7] and 38.0 weeks [SD=3.3], respectively; P=.014).\n Although nicotine gum did not increase quit rates, use of nicotine gum increased birth weight and gestational age, two key parameters in predicting neonatal wellbeing.", "To assess the effect of nicotine patches on continine-validated smoking cessation in pregnant women and the effect of nicotine on birth weight and preterm delivery.\n Pregnant women who smoked ten or more cigarettes after the first trimester (N = 250) were randomly assigned to receive nicotine patches (n = 124) or placebo patches (n = 126). Women randomized to nicotine were treated with 15-mg patches (16 hours/day) for 8 weeks, and 10-mg patches (16 hours/day) for 3 weeks.\n Overall, 26% stopped smoking and 14% were nonsmokers 1 year after delivery. There was no difference between nicotine and placebo groups. At the end of the intervention, the mean value of cotinine in saliva in women assigned to nicotine was 120 ng/mL and placebo 153 ng/mL (mean difference -33; 95% CI -72, 6 ng/mL). Mean birth weight difference was 186 g (95% CI 35, 336 g) higher in the nicotine than placebo group, and there was an insignificantly lower rate of low birth weight (under 2500 g) in the former group. There was no difference in the rate of preterm delivery between the two groups.\n Nicotine patches had no influence on smoking cessation during pregnancy, although they might increase birth weight in comparison with placebo.", "Nicotine-replacement therapy is effective for smoking cessation outside pregnancy and its use is widely recommended during pregnancy. We investigated the efficacy and safety of nicotine patches during pregnancy.\n We recruited participants from seven hospitals in England who were 16 to 50 years of age with pregnancies of 12 to 24 weeks' gestation and who smoked five or more cigarettes per day. Participants received behavioral cessation support and were randomly assigned to 8 weeks of treatment with active nicotine patches (15 mg per 16 hours) or matched placebo patches. The primary outcome was abstinence from the date of smoking cessation until delivery, as validated by measurement of exhaled carbon monoxide or salivary cotinine. Safety was assessed by monitoring for adverse pregnancy and birth outcomes.\n Of 1050 participants, 521 were randomly assigned to nicotine-replacement therapy and 529 to placebo. There was no significant difference in the rate of abstinence from the quit date until delivery between the nicotine-replacement and placebo groups (9.4% and 7.6%, respectively; unadjusted odds ratio with nicotine-replacement therapy, 1.26; 95% confidence interval, 0.82 to 1.96), although the rate was higher at 1 month in the nicotine-replacement group than in the placebo group (21.3% vs. 11.7%). Compliance was low; only 7.2% of women assigned to nicotine-replacement therapy and 2.8% assigned to placebo used patches for more than 1 month. Rates of adverse pregnancy and birth outcomes were similar in the two groups.\n Adding a nicotine patch (15 mg per 16 hours) to behavioral cessation support for women who smoked during pregnancy did not significantly increase the rate of abstinence from smoking until delivery or the risk of adverse pregnancy or birth outcomes. However, low compliance rates substantially limited the assessment of safety. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Current Controlled Trials number, ISRCTN07249128.).", "Stopping smoking in pregnancy is a public health priority and a clinical imperative. However, many women who have not been able to 'quit' in early pregnancy find it very difficult to do so. This randomised-controlled pilot study examined feasibility issues in offering free nicotine patches with counselling to a group of 20 mid-trimester pregnant women at the Women's and Children's Hospital, Adelaide. A further 20 were offered counselling only. Smoking status at each visit was measured by self-report, carbon monoxide monitoring, and salivary cotinine. The most common pattern (eleven of the twenty women) was intermittent patch use. Only five women used patches continuously up to the 12 week maximum available. Three women in the patch group were abstinent at delivery compared with none in the control group. Notable features of the study were the low interest in participation and the high withdrawal rate. Nicotine patches may not be highly useful for pregnant women. Continuing tobacco control measures and customized support for women and their partners, often smokers, may prove more fruitful.", "This study examines whether adding nicotine replacement therapy (NRT) to cognitive-behavioral therapy (CBT) for pregnant smokers increases rates of smoking cessation.\n An open-label randomized trial (Baby Steps, n=181) of CBT-only versus CBT+NRT (choice of patch, gum, or lozenge; 1:2 randomization) was used. Data were collected from 2003 through 2005; analyses were conducted in 2006 and 2007. Outcomes were biochemically validated self-reported smoking status at 7 weeks post-randomization, 38 weeks gestation, and 3 months postpartum.\n Women in the CBT+NRT arm were almost three times more likely than women in the CBT-only arm to have biochemically validated cessation at both pregnancy time points (after 7 weeks: 24% vs 8%, p=0.02; at 38 weeks gestation: 18% vs 7%, p=0.04), but not at 3 months postpartum (20% vs 14%, p=0.55). Recruitment was suspended early by an Independent Data and Safety Monitoring Board when an interim analysis found a higher rate of negative birth outcomes in the CBT+NRT arm than in the CBT-only arm. In the final analysis, the difference between the arms in rate of negative birth outcomes was 0.09 (p=0.26), when adjusted for previous history of preterm birth.\n The addition of NRT to CBT promoted smoking cessation in pregnant women. This effect did not persist postpartum. More data are needed to determine safety parameters and to confirm the efficacy of NRT use during pregnancy." ]

[ "2403655", "10873356", "19673597", "20926017", "11063500", "2403697", "9776150", "7480237", "16989011" ]

[ "Perioperative antibiotic prophylaxis for herniorrhaphy and breast surgery.", "Antibiotic prophylaxis for post-operative wound infection in clean elective breast surgery.", "Does preoperative core needle biopsy increase surgical site infections in breast cancer surgery? Randomized study of antibiotic prophylaxis.", "Effect of local gentamicin application on healing and wound infection in patients with modified radical mastectomy: a prospective randomized study.", "Clarithromycin attenuates mastectomy-induced acute inflammatory response.", "A prospective, randomized double-blind study of the use of antibiotics at the time of mastectomy.", "Prospective, randomized, double-blind study of prophylactic antibiotics in axillary lymph node dissection.", "A prospective, double-blind, placebo-controlled trial of a single dose of azithromycin on postoperative wound infections in plastic surgery.", "Randomized clinical trial of single-dose antibiotic prophylaxis for non-reconstructive breast surgery." ]

[ "We assessed the efficacy of perioperative antibiotic prophylaxis for surgery in a randomized, double-blind trial of 1218 patients undergoing herniorrhaphy or surgery involving the breast, including excision of a breast mass, mastectomy, reduction mammoplasty, and axillary-node dissection. The prophylactic regimen was a single dose of cefonicid (1 g intravenously) administered approximately half an hour before surgery. The patients were followed up for four to six weeks after surgery. Blinding was maintained until the last patient completed the follow-up and all diagnoses of infection had been made. The patients who received prophylaxis had 48 percent fewer probable or definite infections than those who did not (Mantel-Haenszel risk ratio, 0.52; 95 percent confidence interval, 0.32 to 0.84; P = 0.01). For patients undergoing a procedure involving the breast, infection occurred in 6.6 percent of the cefonicid recipients (20 of 303) and 12.2 percent of the placebo recipients (37 of 303); for those undergoing herniorrhaphy, infection occurred in 2.3 percent of the cefonicid recipients (7 of 301) and 4.2 percent of the placebo recipients (13 of 311). There were comparable reductions in the numbers of definite wound infections (Mantel-Haenszel risk ratio, 0.49), wounds that drained pus (risk ratio, 0.43), Staphylococcus aureus wound isolates (risk ratio, 0.49), and urinary tract infections (risk ratio, 0.40). There were also comparable reductions in the need for postoperative antibiotic therapy, non-routine visits to a physician for problems involving wound healing, incision and drainage procedures, and readmission because of problems with wound healing. We conclude that perioperative antibiotic prophylaxis with cefonicid is useful for herniorrhaphy and certain types of breast surgery.", "Antibiotic prophylaxis has been used to good effect in the prevention of post-operative wound infections in patients undergoing gastrointestinal operations. We have assessed the use of a single dose of intravenous antibiotic (Augmentin 1.2 g), given with induction of anaesthesia as prophylaxis, against post-operative wound infection in women undergoing clean, elective breast surgery. Three hundred and thirty-four patients were recruited. Of the 164 receiving antibiotic prophylaxis 29 (17.7%) had wound infections compared with 32 (18.8%) in the placebo group (P=0.79). There were no significant differences in any other post-operative infective complications. Antibiotic prophylaxis is probably not required in clean, elective breast surgery.\n Copyright 2000 Harcourt Publishers Ltd.", "Preoperative core needle biopsies may increase the risk of surgical site infection (SSI) in breast cancer surgery. The purpose of this randomized trial was to determine whether a prophylactic antibiotic would prevent SSI under these conditions.\n Imaging-guided multiple core needle biopsies were performed one to two weeks prior to surgery to obtain confirmation of the presence of breast cancer. Then the patients were randomized to receive either a single intravenous dose of 1.0 g of dicloxacillin (n = 144) or placebo infusion of saline (n = 148) 30 min prior to operation. After breast surgery, incisional morbidity was monitored for 30 days. The number of SSIs was compared with that in 672 patients treated before the implementation of core needle biopsies.\n The patient characteristics and risk factors for SSI were similar in the antibiotic prophylaxis and placebo groups. The incidence of SSI was 7.2% (21/292) in the prospective trial compared with 6.8% (46/672) in the retrospective cohort (p = 0.890). The incidence of postoperative SSIs was 5.6% (8/144) in the dicloxacillin group and 8.8% (13/148) in the placebo group (p = 0.371). For the first two weeks, there was a non-significant trend to fewer SSIs in the antibiotic group (n = 1) than the placebo group (n = 4). Body mass index, smoking, or previous illness did not affect the likelihood of SSI.\n Core needle biopsy did not increase the incidence of SSI. Antibiotic prophylaxis did not prevent SSI, probably because so few infections occurred.", "This study investigated the effects of Gentacoll implants on healing in patients (n = 44) undergoing modified radical mastectomy and axillary dissection. Group I, the Gentacoll group (n = 22), underwent surgery followed by insertion of 10 × 10 × 0.5 cm Gentacoll implants (280 mg collagen sponge plus 200 mg gentamicin sulphate) into the axillary area and under the flap area of the breast before wound closure. Group II, the control group (n = 22), underwent surgery without the application of Gentacoll. Neither group received oral or parenteral post-operative antibiotic therapy. Outcome measures included wound infection, seroma formation, total drainage volumes, drain removal time and duration of hospital stay. Post-operative infection rate, seroma formation, drainage volumes and duration of hospital stay were significantly reduced in the Gentacoll group compared with the control group. In conclusion, the application of Gentacoll significantly improved post-operative outcomes in patients undergoing modified radical mastectomy.", "Based on the observation that administration of clarithromycin led to an attenuation of the inflammatory response induced by surgical trauma in a guinea pig model, we investigated the potential beneficial effects of clarithromycin on the local and systemic inflammatory response in patients undergoing mastectomy in an open-label prospective study. During a 16-month period, 54 patients who underwent mastectomy were randomly divided into two groups. In one group, the patients received oral clarithromycin at a dose of 500 mg twice a day, from the day before to 3 days after mastectomy. There was no significant difference in the incidence of antibiotic prophylaxis-related toxicities or postoperative infections between the patients who received clarithromycin and those who did not. Clarithromycin treatment was significantly associated with an attenuation of febrile response, tachycardia, tachypnea, and an increase in monocyte counts (P, <0.0001, <0.01, <0.05, and <0.01, respectively). Clarithromycin also reduced the intensity and duration of postoperative pain (P, <0.05 and <0.005, respectively) and increased the range of motion of the involved shoulder (P < 0.05 for abduction and flexion). We conclude that clarithromycin effectively modulates the acute inflammatory response associated with mastectomy and produces a better clinical outcome.", "The ability of perioperative cefazolin to reduce the incidence of postoperative wound infection in patients undergoing ablative surgical treatment for carcinoma of the breast was tested in this prospective, randomized, double-blinded study. From May 1983 until December 1985, 118 women were divided into two groups at random. Group 1 consisted of 59 patients and received cefazolin and group 2 was made up of 59 patients who received a placebo. The groups were similar with respect to age, operative procedure, operative time and time to discharge after operation. Three infections occurred among those in group 1 and five among those in group 2 (p = 0.72). The time to onset of infection was delayed in the patients in group 1 versus those in group 2 (17.7 days versus 9.6 days, p = 0.04). Six of eight infections occurred in patients in whom an interval between biopsy and definitive surgical treatment was present. Prophylactic antibiotics in mammary operations did not reduce postoperative wound infections in this study.", "Antibiotic prophylaxis is controversial in patients undergoing axillary lymph node dissection (ALND). We determined whether preoperative antibiotics decreased incidence or treatment cost of infectious complications following ALND.\n Two hundred patients entered this prospective, randomized, double-blind trial. Patients received either placebo or cefonicid preoperatively. Loco-regional signs of infection were monitored for 4 weeks postoperatively.\n There was a trend toward fewer infections in the prophylactic group (placebo 13% versus cefonicid 6%; P = 0.080). Cefonicid significantly decreased severe infections requiring hospitalization (placebo 8% versus cefonicid 1%; P = 0.033). Cefonicid also decreased the treatment cost of infection per patient ($49.80 versus $364.87).\n We demonstrated a trend toward fewer overall infections and significantly fewer severe infections in patients given prophylactic antibiotics, which translated into a decrease in the cost of treatment for infectious complications. These findings support antibiotic prophylaxis for patients undergoing ALND.", "Over a 9-month period from September of 1991 to May of 1992, 339 patients were included in a randomized, double-blind, placebo-controlled study using azithromycin as the prophylactic agent to determine whether it effects a clinically meaningful reduction in postoperative surgical infections in plastic surgery. Azithromycin was given as prophylaxis in 171 patients and placebo in 168 patients. The study medication was a single oral dose taken at 8 P.M. the day before surgery. The patients were followed up for a minimum of 4 weeks after surgery. The patients who received wound infection prophylaxis had 5.1 percent infections compared with 20.5 percent in the placebo group (p = 0.00009). Eighty percent of all wound infections were first seen after discharge, explaining why plastic surgeons might overlook their infectious complications. There was a significant reduction in postoperative complications (p = 0.04) and in the additional use of antibiotics postoperatively (p = 0.007) in the prophylaxis group. Subgroup analysis showed a significant reduction in surgical infections in breast surgery (p < 0.05) and reconstructive surgery with flaps (p < 0.05). No effect of the prophylactic regime was demonstrated in patients undergoing secondary surgery for cleft lip and palate disease.", "The aim of this randomized clinical trial was to determine whether a single intravenous dose of 2 g flucloxacillin could prevent wound infection after primary non-reconstructive breast surgery.\n The study included 618 patients undergoing local excision (n = 490), mastectomy (n = 107) or microdochectomy (n = 21). Patients were randomized to receive either a single dose of flucloxacillin immediately after the induction of anaesthesia or no intervention. Wound morbidity was monitored by an independent research nurse for 42 days after surgery.\n The incidence of wound infection was similar in the two groups: 10 of 311 (3.2 percent) in the flucloxacillin group and 14 of 307 (4.6 percent) in the control group (chi(2) = 0.75, P = 0.387; relative risk 0.71, 95 percent confidence interval 0.32 to 1.53). The groups also had similar wound scores and rates of moderate or severe cellulitis. Wound infection presented a median of 16 days after surgery.\n The administration of a single dose of flucloxacillin failed to reduce the rate of wound infection after non-reconstructive breast surgery." ]