Datasets:

allenai

/

cochrane_dense_mean

like 0

[ "17700083", "10784079", "11144634", "14560166", "8567611", "2702862", "14622893", "17076751", "7539121" ]

[ "A randomized, controlled trial of a home-based intervention program for children with autism and developmental delay.", "Multi-method psycho-educational intervention for preschool children with disruptive behavior: preliminary results at post-treatment.", "A preschool program for safety and injury prevention delivered by home visitors.", "Brief psychoeducational parenting program: an evaluation and 1-year follow-up.", "A treatment outcome study for sexually abused preschool children: initial findings.", "Type of day-care and preschool intellectual development in disadvantaged children.", "Promoting health and home safety for children of parents with intellectual disability: a randomized controlled trial.", "Randomised controlled trial of a parenting intervention in the voluntary sector for reducing child conduct problems: outcomes and mechanisms of change.", "A randomized clinical trial of home intervention for children with failure to thrive." ]

[ "This study aimed to (1) investigate whether provision of a home-based program in addition to a center-based program improves development in young children with disabilities and coping abilities of their families and (2) describe the characteristics of children and families who benefit most from the intervention.\n Fifty-nine children, aged 3-5 years, with no cerebral palsy, participated in the study. Half of the group was randomized to receive an additional program in their homes. A special education teacher provided 40 visits over 12 months working with the families to help generalize skills to the home environment and assist with their concerns. All children were assessed before and after the intervention, and families completed questionnaires assessing family stress, support, and empowerment on both occasions. Differences in change over time and between the intervention and control group were analyzed by repeated measures and the association between characteristics of children and families with improved outcome by multivariate analysis of variance.\n Change in cognitive development and behavior (in the centers) over time favored the children who received the extra intervention (p = .007 and p = .007, respectively). The groups did not differ on any of the family measures of change. Multivariate analysis of variance revealed more improvement for children in the intervention group from higher than lower stressed families.\n Results suggest the need for daily reinforcement of skills learned at the center-based program and the importance of involving families, especially those with few resources and relatively high stress.", "Annual screenings of preschool children at kindergarten registration identified 158 children having high levels of aggressive, hyperactive, impulsive, and inattentive behavior. These \"disruptive\" children were randomly assigned to four treatment conditions lasting the kindergarten school year: no treatment, parent training only, full-day treatment classroom only, and the combination of parent training with the classroom treatment. Results showed that parent training produced no significant treatment effects, probably owing largely to poor attendance. The classroom treatment produced improvement in multiple domains: parent ratings of adaptive behavior, teacher ratings of attention, aggression, self-control, and social skills, as well as direct observations of externalizing behavior in the classroom. Neither treatment improved academic achievement skills or parent ratings of home behavior problems, nor were effects evident on any lab measures of attention, impulse control, or mother-child interactions. It is concluded that when parent training is offered at school registration to parents of disruptive children identified through a brief school registration screening, it may not be a useful approach to treating the home and community behavioral problems of such children. The kindergarten classroom intervention was far more effective in reducing the perceived behavioral problems and impaired social skills of these children. Even so, most treatment effects were specific to the school environment and did not affect achievement skills. These findings must be viewed as tentative until follow-up evaluations can be done to determine the long-term outcomes of these interventions.", "To evaluate the feasibility, acceptability, and effectiveness of an injury prevention program delivered by school based home visitors to the families of low income children attending preschool enrichment programs in Washington State.\n The families of children attending preschool Head Start programs in two regions were eligible. A total of 213 families (77.8% of those eligible) from intervention sites, and 149 families (71.9% of those eligible) from concurrent comparison sites, agreed to participate and completed the trial.\n Trained school personnel conducted home safety inspections as part of a planned home visit. Intervention families were offered educational materials as well as smoke detectors, batteries, ipecac, and age appropriate car safety restraints based on results of the home inspection.\n At a repeat home visit three months later, the proportion of families with a positive change in injury prevention knowledge or behavior among those in the intervention group was compared with the proportion in the comparison group. Smoke detector presence and function were observed.\n Among families without a working smoke detector at baseline, the intervention was associated with an increased probability of having a working detector at follow up (relative risk (RR) 3.3, 95% confidence interval (CI) 1.3 to 8.6). Intervention families were also more likely to report the presence of ipecac in the home (RR 4.7, 95% CI 3.0 to 7.3) at follow up and to have obtained an age appropriate booster seat (RR 4.1, 95% CI 1.9 to 8.8). The program was acceptable to client families and to the home visitors who conducted the intervention.\n Among the families of low income children enrolled in preschool enrichment programs, home safety inspections and the distribution of safety supplies by school based home visitors appears to improve knowledge and behavior related to poisoning, smoke detector installation, and car safety seat use over three months of follow up.", "Despite recognition of the need for parenting interventions to prevent childhood behavioral problems, few community programs have been evaluated. This report describes the randomized controlled evaluation of a four-session psychoeducational group for parents of preschoolers with behavior problems, delivered in community agencies.\n In 1998, 222 primary caregivers, recruited through community ads, filled out questionnaires on parenting practices and child behavior. Parents were randomly assigned to immediate intervention or a wait-list control. The intervention comprised three weekly group sessions and a 1-month booster, the focus being to support effective discipline (using the video 1-2-3 Magic) and to reduce parent-child conflict.\n Using an intent-to-treat analysis, repeated-measures analyses of variance indicated that the parents who received the intervention reported significantly greater improvement in parenting practices and a significantly greater reduction in child problem behavior than the control group. The gains in positive parenting behaviors were maintained at 1-year follow-up in a subset of the experimental group.\n This brief intervention program may be a useful first intervention for parents of young children with behavior problems, as it seems both acceptable and reasonably effective.", "Treatment outcome for sexually abused preschool-age children and their parents was assessed, comparing the effectiveness of a cognitive-behavioral intervention to nondirective supportive treatment.\n Sixty-seven sexually abused preschool children and their parents were randomly assigned to either (1) cognitive-behavioral therapy adapted for sexually abused preschool children (CBT-SAP) or (2) nondirective supportive therapy (NST). Treatment consisted of 12 individual sessions for both the child and parent, monitored for integrity with the therapeutic model through intensive training and supervision, use of treatment manuals, and rating of audiotaped sessions. Parents completed the Child Behavior Checklist, the Child Sexual Behavior Inventory, and the Weekly Behavior Report to measure a variety of emotional and behavioral symptoms.\n Within-group comparison of pretreatment and posttreatment outcome measures demonstrated that while the NST group did not change significantly with regard to symptomatology, the CBT-SAP group had highly significant symptomatic improvement on most outcome measures. Repeated-measures analyses of variance demonstrated group x time interactions on some variables as well. Clinical findings also supported the effectiveness of the CBT-SAP intervention over NST.\n Findings provide strong preliminary evidence for the effectiveness of a specific cognitive-behavioral treatment model for sexually abused preschool children and their parents.", "Levels and patterns of intellectual development of 3 groups of socioeconomically disadvantaged children were compared. The groups consisted of (1) children who were randomly assigned to receive extensive university-based intervention group day-care, (2) children whose parents placed them in community day-care centers for varying amounts of time, or (3) children whose parents chose little to no center-based day-care for their children. Two repeated-measures analyses of variance were performed to identify possible day-care effects on IQ level and on patterns of infant and preschool cognitive development. The results suggest that quality community day-care, as well as intervention day-care, may positively change both the level and pattern of preschool intellectual development of socioeconomically disadvantaged children.", "The objective of this study was to evaluate the efficacy of a home-based intervention targeted to parents with intellectual disability to promote child health and home safety in the preschool years. A total of 63 parents were recruited for the study with 45 parents (40 mothers and 5 fathers) from 40 families completing the project. The research design permitted comparison between the intervention and three alternative conditions with all parents receiving the intervention in an alternating sequence over the life of the project. The intervention consisted of 10 weekly lessons carried out in the parent's home focusing on child health and home safety. The program was adapted to suit the Australian context from the UCLA Parent--Child Health and Wellness Project (Tymchuk, Groen, & Dolyniuk, 2000). Outcome measures assessed parental health and safety behaviours. Standard measures included parental health, intelligence and literacy. The intervention improved parents' ability to recognize home dangers, to identify precautions to deal with these dangers and resulted in a significant increase in the number of safety precautions parents implemented in their homes with all gains being maintained at 3 months post-intervention. Parents' health behaviours including improved understanding of health and symptoms of illness, knowledge of and skills needed to manage life-threatening emergencies, knowledge about visiting the doctor, knowing when to call, what information to provide and what questions to ask, and how to use medicines safely significantly increased. Again, all gains were maintained 3 months post-intervention. The intervention was effective regardless of parental health, literacy skills, and IQ. This form of home-based intervention promotes a healthy and safe environment which is a prerequisite to continuing parental custody.", "To test effectiveness of a parenting intervention, delivered in a community-based voluntary-sector organisation, for reducing conduct problems in clinically-referred children.\n Randomised controlled trial, follow-up at 6, 18 months, assessors blind to treatment status. Participants--76 children referred for conduct problems, aged 2-9, primarily low-income families, randomised to treatment vs. 6-month wait-list group. Retention was 93% at 6 months, 90% at 18 months. Interventions--Webster-Stratton Incredible Years video-based 14-week group programme, teaches cognitive-behavioural principles for managing behaviour, using a collaborative, practical, problem-solving approach. Primary outcomes--child problem behaviour by parent-report (Eyberg) and home-based direct observation; secondary outcomes--observed positive and negative parenting; parent-reported parenting skill, confidence and depression.\n Post-treatment improvements were found in child problem behaviour, by parent-report (effect size (ES) .48, p = .05) and direct observation (ES .78, p = .02); child independent play (ES .77, p = .003); observed negative (ES .74, p = .003) and positive (ES .38, p = .04) parenting; parent-reported confidence (ES .40, p = .03) and skill (ES .65, p =.01), using ANCOVA to control for baseline scores. Maternal depression did not change. Consumer satisfaction was high. At 18-month follow-up, although no randomised comparison was possible, changes appeared to maintain, with no significant change toward baseline level on any measure. Change in observed positive parenting appeared to mediate change in child problem behaviour (p < .025).\n Findings suggest that a group-based cognitive-behavioural parenting programme, delivered by well-trained and supervised staff, can be effective in a community voluntary-sector setting, for reducing conduct problems and enhancing parenting skills. Change in parenting skill appears to be a key mechanism for change in child behaviour. Findings have implications for feasibility of translating evidence-based programmes, even for clinically-referred conduct problems, into less specialised community settings, likely to have lower costs and be more accessible for families.", "To evaluate the efficacy of a home-based intervention on the growth and development of children with nonorganic failure to thrive (NOFTT).\n Randomized clinical trial.\n The NOFTT sample included 130 children (mean age, 12.7 months; SD, 6.4) recruited from urban pediatric primary care clinics serving low income families. All children were younger than 25 months with weight for age below the fifth percentile. Eligibility criteria included gestational age of at least 36 weeks, birth weight appropriate for gestational age, and no significant history of perinatal complications, congenital disorders, chronic illnesses, or developmental disabilities. Children were randomized into two groups: clinic plus home intervention (HI) (n = 64) or clinic only (n = 66). There were no group differences in children's age, gender, race, or growth parameters, or on any of the family background variables. Most children were raised by single, African-American mothers who received public assistance. Eighty-nine percent of the families (116 of 130) completed the 1-year evaluation.\n All children received services in a multidisciplinary growth and nutrition clinic. A community-based agency provided the home intervention. Families in the HI group were scheduled to receive weekly home visits for 1 year by lay home visitors, supervised by a community health nurse. The intervention provided maternal support and promoted parenting, child development, use of informal and formal resources, and parent advocacy.\n Growth was measured by standard procedures and converted to z scores for weight for height and height for age to assess wasting and stunting. Cognitive and motor development were measured with the Bayley Scales of Infant Development, and language development was measured by the Receptive/Expressive Emergent Language Scale. Both scales were administered at recruitment and at the 12-month follow-up. Parent-child interaction was measured by observing mothers and children during feeding at recruitment and at the 12-month follow-up, and the quality of the home was measured by the Home Observation Measure of the Environment 18 months after recruitment.\n Repeated-measures multivariate analyses of covariance were used to examine changes in children's growth and development and parent-child interaction. Analyses of covariance were used to examine the quality of the home. Independent variables were intervention status and age at recruitment (1.0 to 12.0 vs 12.1 to 24.9 months). Maternal education was a covariate in all analyses. When changes in developmental status and parent-child interaction were examined, weight for height and height for age at recruitment were included as covariates.\n Children's weight for age, weight for height, and height for age improved significantly during the 12-month study period, regardless of intervention status. Children in the HI group had better receptive language over time and more child-oriented home environments than children in the clinic-only group. The impact of intervention status on cognitive development varied as a function of children's ages at recruitment, with younger children showing beneficial effects of home intervention. There were no changes in motor development associated with intervention status. During the study period, children gained skills in interactive competence during feeding, and their parents became more controlling during feeding, but differences were not associated with intervention status.\n Findings support a cautious optimism regarding home intervention during the first year of life provided by trained lay home visitors. Early home intervention can promote a nurturant home environment effectively and can reduce the developmental delays often experienced by low income, urban infants with NOFTT: Subsequent investigations of home intervention should consider alternative options for toddlers with NOFTT:" ]

[ "17194269", "16585434", "11481167", "9989566", "18562423", "9131723", "8610833", "11041534", "16449469" ]

[ "A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition.", "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.", "A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia.", "Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response.", "Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial.", "Improvement of cognitive function in schizophrenic patients receiving clozapine or zotepine: results from a double-blind study.", "Different side effect profiles of risperidone and clozapine in 20 outpatients with schizophrenia or schizoaffective disorder: a pilot study.", "Risperidone versus clozapine in treatment-resistant schizophrenia: a randomized pilot study.", "Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics." ]

[ "Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy.\n This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003.\n Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group.\n Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function.", "When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.\n Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).\n Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.\n For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.", "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.", "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.", "Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred. We aimed in validating the add-on of ziprasidone and risperidone to clozapine, and we performed a randomised head-to-head trial. Patients with partial response to clozapine were randomly attributed to augmentation with ziprasidone (n = 12) or risperidone (n = 12). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Furthermore, several safety and tolerability measures were obtained. After six weeks, both groups showed significant reductions of positive and negative symptoms. In addition, affective state, psychosocial functioning and clozapine side effects improved without significant differences between the groups. Both approaches were well tolerated. However, the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms. Patients under clozapine-risperidone therapy developed a rise of serum prolactin levels. The clozapine augmentation with ziprasidone or risperidone resulted in significant psychopathological improvements. The side effects differed between the treatment groups. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary.", "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 side effect +profiles of clozapine and risperidone.\n The subjects were 20 outpatients with schizophrenia or schizoaffective disorder who were clinically stable on a regimen of clozapine at the time of screening. They underwent a randomized-order crossover comparison of 6 weeks of risperidone treatment and 6 weeks of clozapine treatment. Clinical and neurocognitive variables were assessed by raters blind to medication status, and severity of side effects was determined from patients' self-reports.\n Side effect measures, but not clinical ratings, were significantly different after 6 weeks of treatment with the two drugs. Patients required more benztropine for motor effects and complained of more insomnia with risperidone and more sedation with clozapine. Body weight was higher at the end of clozapine treatment than at the end of risperidone treatment.\n In this exploratory study, the side effect profiles of clozapine and risperidone were consistent with the different pharmacodynamic profiles of the two drugs.", "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.", "In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome.\n The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug.\n Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings.\n Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies." ]

[ "380773", "12911781", "16176400", "10992533", "366350", "7662102", "11754675", "7852667", "12687385" ]

[ "Flunisolide nasal spray for perennial rhinitis in children.", "Usefulness of specific immunotherapy in patients with severe perennial allergic rhinitis induced by house dust mite: a double-blind, randomized, placebo-controlled trial.", "Three-year follow-up of clinical and inflammation parameters in children monosensitized to mites undergoing sub-lingual immunotherapy.", "Influence of intranasal steroids during the grass pollen season on bronchial responsiveness in children and young adults with asthma and hay fever.", "Beclomethasone dipropionate aerosol in the treatment of children with severe perennial rhinitis.", "Efficacy of the acaricide: acardust for the prevention of asthma and rhinitis due to dust mite allergy, in children.", "Comparison of cefuroxime with or without intranasal fluticasone for the treatment of rhinosinusitis. The CAFFS Trial: a randomized controlled trial.", "Effect of intranasal azelastine and beclomethasone dipropionate on nasal symptoms, nasal cytology, and bronchial responsiveness to methacholine in allergic rhinitis in response to grass pollens.", "Comparison of once- versus twice-daily use of beclomethasone dipropionate aqueous nasal spray in the treatment of allergic and non-allergic chronic rhinosinusitis." ]

[ "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.", "To evaluate the effectiveness of specific immunotherapy (SIT) in patients with severe house dust mite (HDM)-induced perennial allergic rhinitis using diary cards and objective endpoints.\n Thirty-six adult patients were selected with moderate to severe allergic rhinitis due to HDM allergy uncontrolled by regular anti-allergic drugs. Twenty-eight patients completed the study, 22 of these patients also had mild asthma. Subjects were stratified for HDM sensitivity on the basis of their 4-week diary card score and the size of their immediate and late-phase skin reaction to HDM. The groups were well matched for all relevant parameters. Patients were randomized to receive active preparation (Alutard(R)-SQ, ALK, Dermatophagoides pteronyssinus extract) or an identical placebo preparation. Increasing doses were administered until the maintenance dose was reached. This dose was then given once a month for 12 months.\n Clinical efficacy was evaluated by symptom medication diary cards recorded for 4 weeks after 12 months of continuous treatment and compared with pre-treatment scores. Skin test reactivity was re-measured after 12 months of treatment to HDM, cat dander and codeine phosphate. After 1 year of treatment, the actively treated group showed a 58% reduction in diary card symptom scores (P<0.002) and a 20% reduction in the use of rescue medication. The placebo group had a 32% reduction in symptom scores (P=NS), but no reduction in rescue medication requirements. The active group showed 36% reduction in skin prick test sensitivity to D. pteronyssinus (P=0.006), while the placebo group values were unchanged. Skin reactivity to codeine was unchanged in both groups. No significant adverse reactions to SIT were encountered.\n One year of SIT for D. pteronyssinus in patients with poorly controlled rhinitis (+/-mild asthma) produced clinically useful improvement as shown by symptom-medication diary cards and reductions in immediate skin reactions compared with placebo treatment.", "Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy (SLIT) is highly beneficial. Twenty-four children (age 4-16) monosensitized to house dust mite were randomized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657-62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic protein (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite-specific immunoglobulin E (IgE) were recorded before treatment and at 10-12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study. In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment.", "It has been reported that intranasal corticosteroids can influence bronchial hyperresponsiveness (BHR) in asthmatic subjects with seasonal rhinitis. The purpose of the present study was to evaluate the effect of intranasal fluticasone propionate and beclomethasone dipropionate on BHR and bronchial calibre (forced expiratory volume in one second, FEV(1)) in children and young adults with seasonal rhinitis and mild asthma during two consecutive grass pollen seasons.\n In the first pollen season 25 patients aged 8-28 years were included in a double blind, placebo controlled study. The active treatment group used fluticasone aqueous spray 200 microgram once daily. In the second pollen season 72 patients aged 8-28 years participated in a double blind, placebo controlled study of a similar design to that of the previous year except that an additional treatment group of patients using beclomethasone 200 microg twice daily was included. FEV(1) was measured before and after three and six weeks of treatment; BHR to methacholine (PD(20)) was measured before and after six weeks of treatment.\n In the first season the mean (SD) logPD(20) of the patients decreased significantly both in the fluticasone group (from 2.43 (0.8) microgram to 1.86 (0.85) microgram) and in the placebo group (from 2.41 (0.42) microgram to 1.87 (0.78) microgram) without any intergroup difference in the change in logPD(20). In the second pollen season the mean logPD(20) in the fluticasone, beclomethasone, and placebo groups did not change significantly.\n Intranasal steroids did not influence BHR during two grass pollen seasons in children and young adults with seasonal rhinitis and mild asthma.", "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, randomized, comparative study versus placebo, was done during 6 months in 32 children, aged 4-12 years, who suffer from either allergic asthma or rhinitis or both, slept in a bedroom rich in dust mite, have well documented allergy solely to house dust mite (H.D.M.), and a condition severe enough to require continuous medication. After thorough cleaning, their bedrooms were sprayed on day 0 and day 90 with the total content of a canister containing either Acardust or Placebo. Rooms were cleaned regularly throughout the study period. Each child completed an individual daily score card (scales from 0-3) for asthma, and rhinitis symptoms, medication taken, and any additional symptoms. Peak flow was recorded twice weekly. All the children were examined every month (at the clinic) when also PFF, FEVI, doctor's and patient's opinion of clinical symptoms were recorded according to the same scale (0-3) and dust samples from child's bedroom were examined for H.D.M. antigen content. At day 0, 90 and 180, total IgE and dust mite specific IgE determination was done. At the end of the study, patient's and doctor's opinion about the spray's efficacy were recorded on a scale from 0-3. The results were in favor of Acardust for asthma, according to patient's opinion (p = 0.001), doctor's opinion (p = 0.04) and individual score cards (p = 0.03), and for nasal secretion (p = 0.01), sneezing and lacrimation (p = 0.02); concurrent medication dropped significantly (p = 0.01) in the Acardust group. No side-effects were reported. We consider Acardust a safe and valuable preventive treatment in H.D.M. allergy.", "It is not known whether intranasal corticosteroids are beneficial to treat acute rhinosinusitis in patients with a history of chronic or recurrent sinus symptoms.\n To assess whether the addition of an intranasal corticosteroid to antibiotic therapy affects the speed and rate of recovery of such patients with acute rhinosinusitis.\n A double-blind, randomized, placebo-controlled multicenter trial of 95 patients (median age, 39 years) with a history of recurrent sinusitis or chronic rhinitis and evidence of acute infection by sinus radiograph or nasal endoscopy, which was conducted from October 1998 through April 2000 at 22 sites (12 primary care and 10 otolaryngology).\n Two puffs (total dose, 200 microgram) of fluticasone propionate (n = 47) or placebo nasal spray (n = 48) in each nostril once daily for 21 days; all received 2 puffs of xylometazoline hydrochloride in each nostril twice daily for 3 days and 250 mg of cefuroxime axetil twice daily for 10 days.\n Time to clinical success (patient reported cured or much improved) during telephone follow-up at 10, 21, and 56 days.\n A total of 88 patients (93%) completed follow-up. Patients recorded their symptoms, work assessment, and compliance during the 3-week treatment phase. Patients receiving fluticasone achieved a significantly higher rate of clinical success than patients receiving placebo (93.5% vs 73.9%; P =.009). Patients treated with fluticasone improved significantly more rapidly (median of 6.0 days to clinical success) vs patients in the placebo group (median of 9.5 days; P =.01).\n The addition of fluticasone to xylometazoline and antimicrobial therapy with cefuroxime improves clinical success rates and accelerates recovery of patients with a history of chronic rhinitis or recurrent sinusitis who present for treatment of acute rhinosinusitis.", "We compared the effect of nasal azelastine (0.56 mg/day), nasal beclomethasone dipropionate (BDP, 200 micrograms/day) and matched placebo on seasonal symptoms, nasal cytology, and the increase in bronchial responsiveness occurring during pollen season in a group of subjects with history of allergic rhinitis to grass pollens only.\n The study was completed by nine subjects in the azelastine group, 13 subjects in the BDP group, and 13 subjects in the placebo group. Treatments were randomly administered for 6 weeks. Each subject recorded daily nasal, eye and chest symptoms and additional treatment requirement for the entire pollen season. Each subject performed nasal lavage 4 weeks into the pollen season. Bronchial responsiveness to methacholine was measured before and 4 weeks into the pollen season. Response was expressed as provocative dose causing a 20% fall in forced expiratory volume in 1 second in micromoles.\n Azelastine-treated subjects had significantly fewer nasal symptoms during week 4 (p < 0.05), and BDP-treated subjects had fewer nasal symptoms during week 4 (p < 0.05) and week 5 (p < 0.05) compared with subjects given placebo. Both treatments significantly reduced the need for additional medications. BDP, but not azelastine, treatment significantly reduced the percent of eosinophils recovered in nasal lavage (p < 0.05). Neither azelastine nor BDP protected against the increase in bronchial responsiveness to methacholine occurring during the pollen season.\n We demonstrated that both azelastine and BDP are effective treatments for nasal symptoms of seasonal allergic rhinitis after 4 weeks of therapy. However, we were not able to demonstrate an antiinflammatory activity of nasally administered azelastine. Nasal therapy with azelastine and BDP did not block the increase in bronchial responsiveness to methacholine caused by seasonal allergen exposure.", "The aim of the study was to assess the efficacy and safety of nasal aqueous beclomethasone dipropionate (BDP), 400 micro g/day, given via a metered pump in a once-daily or twice-daily regimen following a double-blind, parallel group design over a 12-week period. Adult patients (n=112) with allergic or non-allergic chronic rhinosinusitis recorded their nasal and ocular symptoms for the 7-day run-in period and for the first 4 weeks of treatment. At baseline and after 4 weeks the airways' resistance via active anterior rhinomanometry and the volume and area section via acoustic rhinometry were measured. Morning serum cortisol was measured at baseline and at week 12. Adverse events were to be reported at each visit. Of the 112 randomised patients, three did not enter the ITT analysis and another 13 in total discontinued the treatment. Significant improvements over the baseline were reported in both groups for the primary variable sum of nasal scores (-53.7% in the once-daily group and -59.7 in the twice-daily group), as well as for each nasal and ocular symptoms, without differences between the groups. Because of a wider variability than expected, the 95% confidence interval (C.I.) for the difference between the least square means exceeded the pre-defined limit of +/-10% of the reference mean. Similar improvements in both groups were also reported for the nasal airway patency's parameters. The total number of drug-related adverse events was 26 in the once-daily group and 32 in the twice-daily group, with most of the events consisting of local effects at the site of application. No signs of adrenal suppression were observed, and serum morning cortisol values did not significantly change. The once-daily BDP dosing (400 micro g/day) therefore has a similar efficacy and safety profile as the same daily dose given in a twice-daily regimen." ]

[ "2407200", "3897499", "9105740", "10207925", "12763331", "2926574", "17666597", "12878450", "10103305" ]

[ "Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation. Ventriculomegaly Trial Group.", "Serial lumbar punctures in prevention of post-hemorrhagic hydrocephalus in preterm infants.", "Failure of fibrinolytic endoventricular treatment to prevent neonatal post-haemorrhagic hydrocephalus. A case-control trial.", "Acetazolamide and furosemide for posthemorrhagic hydrocephalus of the newborn.", "Intraventricular streptokinase for the treatment of posthaemorrhagic hydrocephalus of preterm.", "Posthemorrhagic hydrocephalus in high-risk preterm infants: natural history, management, and long-term outcome.", "Antepartum treatment without early cordocentesis for standard-risk alloimmune thrombocytopenia: a randomized controlled trial.", "Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia.", "A randomized, controlled trial of prophylactic granulocyte-macrophage colony-stimulating factor in human newborns less than 32 weeks gestation." ]

[ "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.", "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.", "Post-haemorrhagic hydrocephalus is assumed to result from obstruction of the cerebrospinal fluid (CSF) pathways by blood clots and subsequent chronic infiltration with collagen. The aim of this work was to evaluate the possibility of preventing permanent shunt dependence by enhancing the endoventricular fibrinolysis by means of an endoventricular streptokinase infusion in babies affected by posthaemorrhagic ventricular dilation. A case-control trial was carried out in 12 neonates affected by intraventricular haemorrhage and subsequent progressive ventriculomegaly. Six of them were treated with 20,000 U/day of streptokinase infused over 96 h through a percutaneous ventricular catheter. Our results show that the percentage of shunted babies was identical in treated and control patients despite the enhancement of endoventricular fibrinolysis obtained in all treated patients. On the basis of our results we do not recommend intraventricular streptokinase infusion for routine use in post-haemorrhagic ventricular dilatation.", "The authors evaluated the efficacy of acetazolamide (ACZ) and furosemide (FUR) in avoiding ventricular shunting procedures in preterm infants with posthemorrhagic hydrocephalus (PHH) and increased intracranial pressure (ICP). Preterm infants were screened for PHH (defined as ventriculomegaly [VM] and increased ICP measured with the Ladd fiberoptic monitor). PHH infants were randomized to ACZ and FUR treatment or serial lumbar puncture (LP) and monitored until not receiving medications or having undergone shunting. Of 69 infants with IVH screened for the study, 39 never developed VM, 14 developed VM, without increased ICP, and 16 developed PHH. Ten PHH infants were randomized to ACZ and FUR treatment and six to serial LP. Nine (90%) of the 10 infants assigned to the ACZ and FUR group avoided shunting. Nephrocalcinosis developed in a significant proportion of treated infants. Three (50%) of the six LP group infants did not require shunting procedures (P = 0.118). The authors conclude that ACZ and FUR therapy is useful in the treatment of preterm infants with PHH. Because a significant number of infants treated with both ACZ and FUR developed nephrocalcinosis, close monitoring for increased calcium excretion in the urine, or use of ACZ without FUR, is advised.", "Posthaemorrhagic hydrocephalus following intraventricular haemorrhage is still one of the most serious complications of premature birth. Small premature babies are not suitable for shunt surgery because of high cerebrospinal fluid protein and risk of obstruction. For this reason there is a great need for alternative approaches for treatment of posthaemorrhagic hydrocephalus. The objective of this study was to investigate if intraventricular streptokinase treatment reduces the need for ventriculoperitoneal shunt in posthaemorrhagic hydrocephalus. A case-control trial was carried out in 12 premature babies with posthaemorrhagic hydrocephalus. Six of them were treated with intraventricular streptokinase and 6 premature babies were in the control group. While 5 babies in the study group needed ventriculoperitoneal shunt, 3 of the control patients needed shunt surgery. There were no rebleeding, ventriculitis or meningitis in either groups. In conclusion on the basis of our results we do not recommend routine use of intraventricular streptokinase in posthaemorrhagic hydrocephalus.", "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.", "To evaluate the effectiveness and safety of two antenatal treatment regimens designed to optimally protect fetuses against intracranial hemorrhage resulting from alloimmune thrombocytopenia while minimizing the risks associated with fetal blood sampling. The study was limited to \"standard-risk\" patients, who were defined as women with documented alloimmune thrombocytopenia who had not delivered an infant with an intracranial hemorrhage in a prior pregnancy.\n In this prospective multicenter study of 73 women with documented alloimmune thrombocytopenia, patients were randomized to receive either intravenous immunoglobulin (IVIG) 2 g/kg/wk (group A) or IVIG 1 g/kg/wk plus prednisone 0.5 mg/kg/d (group B), starting at approximately 20 weeks of gestation. Fetal blood sampling was performed at approximately 32 weeks of gestation, and those with fetal platelet counts less than 30,000/mL(3) were given salvage therapy.\n There were two intracranial hemorrhages; neither was due to treatment failure. The average platelet counts at the time of fetal blood sampling were 121,600/mL(3) and 116,100/mL(3), and the average birth platelet counts were 169,400/mL(3) and 134,000/mL(3) for groups A and B, respectively. Twenty-seven percent of patients in group A and 17% in group B received salvage therapy, and only one neonate in each of these subsets had a birth platelet count less than 30,000/mL(3). There were four complications after 79 fetal blood sampling procedures, leading to cesarean deliveries between 32 and 37 weeks. There was a higher incidence of gestational diabetes and a tendency to more fluid retention, mood swings, insomnia, and jitteriness in patients on prednisone and of moderate-to-severe fatigue in those on high-dose IVIG alone.\n The outcomes of both treatment groups were excellent and comparable. Early cordocentesis is not necessary when treating alloimmune thrombocytopenia in patients who have not delivered an infant with an intracranial hemorrhage in a prior pregnancy.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00194987\n I.", "Hypoxic-ischemic encephalopathy (HIE) remains one of the most important neurologic complications in the newborn. Several experimental and clinical studies have shown that hypothermia is the most effective means known for protecting the brain against hypoxic-ischemic brain damage. Furthermore, recent data have suggested that platelet-activating factor (PAF) could play a pathophysiologically important role in the progression of hypoxic-ischemic brain injury. The aim of the present study was to investigate the role of head cooling combined with minimal hypothermia in short-term outcome of infants with perinatal asphyxia. In addition, we have examined the effect of head cooling combined with minimal hypothermia on PAF concentrations in cerebrospinal fluid (CSF) after hypoxic-ischemic brain injury. The group of asphyxiated infants (Group 1) consisted of 21 full-term (gestational age >37 weeks). These infants were randomized and divided into either a standard therapy group (Group 1a; n=10) or cooling group (Group 1b; n=11). Head cooling combined with minimal hypothermia (rectal temperature 36.5-36 degrees C) was started as soon as practicable after birth. The infants were cooled for 72h and then were rewarmed at 0.5 degrees C/h. The control group (Group 2) consisted of seven full-term infants and none of these infants showed any sign of asphyxia. To measure PAF concentration in CSF, CSF with lumbar puncture was collected into tubes immediately before the cooling (1-3h after birth) and again after 36h. We had no evidence of severe adverse events related to hypothermia. In Group 1a, two infants died after 72h of life; however, all newborn infants in Group 1b survived. Convulsion required treatment in three infants of standard therapy group (1a); none of the infants in Group 1b had clinical seizure activity. Abnormal EEG patterns were found in four infants of Group 1a; no EEG abnormalities were noted in Group 1b (P<0.05). On admission (before cooling), PAF concentration in CSF of asphyxiated infants was found to be significantly higher when compared with that of control (P<0.001). Mean PAF concentration before initiation of the study was similar in the two asphyxiated groups (Group 1a vs. 1b) (P>0.05). Obtained PAF level in CSF after 36h, showed a profound decline in cooling group of infants compared to Group 1a infants (P<0.01). In conclusion, the present study suggests that cerebral cooling with minimal hypothermia started soon after birth has no severe adverse effects during 72-h cooling period and that short-term outcome of infants are encouraging. Our results also support the hypothesis PAF an important mediator in hypoxic-ischemic brain injury and demonstrate that head cooling combined with minimal hypothermia reduces the normal increase in PAF following hypoxic-ischemic brain injury in full-term infants.", "Preterm neonates undergoing intensive care have high morbidity from sepsis. These infants also frequently develop neutropenia, and when this is associated with sepsis, mortality is high. This study investigates the potential for granulocyte-macrophage colony-stimulating factor (GM-CSF) to effect a clinically relevant increase in neutrophil number when used prophylactically in high-risk preterm neonates, and assesses its safety in this population.\n In an open, randomized, controlled study, 75 neonates (25 small for gestational age) <32 weeks gestation were randomized to receive GM-CSF (10 microg/kg/d) by subcutaneous injection for 5 days from <72 hours after birth, or to a control group. The primary outcome measure was the neutrophil count during 14 days from study entry. The infants were monitored for potential toxicity. Clinical outcomes, sepsis, and mortality, were recorded, but this initial study was not designed to address clinical benefit.\n Prophylactic GM-CSF therapy completely abolished neutropenia in treated infants, when both well and septic, throughout the period of study. Neutropenia (</=1.7 x 10(9)/L) developed in 16 of 39 control infants. Five control infants experienced an acute decrease in neutrophil count coincident with the onset of sepsis. There was no evidence of hematologic, respiratory, or gastrointestinal toxicity in treated infants. Treated infants had a trend to fewer symptomatic, blood culture positive septic episodes than controls during 2 weeks from study entry (11/36 vs 18/39).\n Five-day prophylactic GM-CSF completely abolishes postnatal neutropenia and sepsis-induced neutropenia in preterm neonates at high risk of sepsis, and so removes an important risk factor for sepsis and sepsis-related mortality.GM-CSF, preterm neonates, neutropenia, sepsis." ]

[ "3479525", "3897460", "6802657", "7119136", "7198209", "6889709", "2642499", "2182613", "9581210" ]

[ "Failure of long term high-dose lecithin to retard progression of early-onset Alzheimer's disease.", "A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease.", "Lecithin treatment of cognitively impaired Parkinson's patients.", "A dose-ranging study of lecithin in the treatment of primary degenerative dementia (Alzheimer disease).", "Alzheimer disease: lack of effect of lecithin treatment for 3 months.", "Lecithin administration in Alzheimer dementia.", "Chronic oral physostigmine without lecithin improves memory in Alzheimer's disease.", "A crossover study of lecithin treatment of tardive dyskinesia.", "Short-term administration of selegiline for mild-to-moderate dementia of the Alzheimer's type." ]

[ "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.", "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.", "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.", "nan", "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.", "nan", "Sixteen patients with early Alzheimer's disease (AD) completed a 3-month outpatient double-blind parallel trial of oral physostigmine versus placebo. Ten subjects received drug; six received placebo. After a dose-titration phase, each patient was placed on his or her best dose of drug or placebo. Subjects were evaluated with both memory and nonmemory tasks. Seven of the ten drug-treated patients, but none of the six placebo-treated patients, demonstrated improvement on a selective reminding task, a test of verbal memory. Family members reported improvement in six of ten drug-treated patients and none of six placebo-treated individuals. There was a trend toward greater improvement with increasing drug dose. There was no improvement on the nonmemory tests administered. The data indicate that oral physostigmine improves memory but not other areas of cognition.", "The authors enrolled 21 patients in a random-order, crossover, double-blind trial of phosphatidylcholine (lecithin) 20 g/day and placebo. Fourteen patients completed at least 6 weeks of the second 8-week trial and were used for efficacy analyses. Side effects were minimal. The lecithin treatment effect--about one half of an Abnormal Involuntary Movement Scale point--was seen as a statistical effect of treatment order, based on differences between patients who took the active compound before or after they took the placebo. Clinically, however, the lecithin effect was negligible.", "As a follow-up to an earlier study showing short-term benefit in inpatients with more severe dementia, the authors studied the short-term cognitive, functional, and behavioral effects of selegiline in outpatients with mild-to-moderate dementia of the Alzheimer type (DAT) by means of a double-blind, randomized, crossover study of placebo vs. selegiline. Fifty outpatients with mild-to-moderate DAT and no behavioral disturbances were given selegiline in two 8-week treatment periods separated by a 4-week washout. Outcome was assessed with standardized measures of dementia severity, daily functioning, behavior, and cognition. There was no drug-placebo difference in any outcome measure. Selegiline did not show short-term benefit in this study, contrary to the earlier study, perhaps because the patients were studied less intensively and/or lacked behavioral problems that could show response, although the medication was well tolerated." ]

[ "15485728", "16157604", "16877628", "20840874", "18718924", "16904951", "9243440", "20484492", "12959796" ]

[ "Telephone reminders are effective in recruiting nonresponding patients to randomized controlled trials.", "Recruiting patients to medical research: double blind randomised trial of \"opt-in\" versus \"opt-out\" strategies.", "Impact of privacy legislation on the number and characteristics of people who are recruited for research: a randomised controlled trial.", "Do messages of scarcity increase trial recruitment?", "Optimising recruitment into a study of physical activity in older people: a randomised controlled trial of different approaches.", "A randomised trial of the effects of an additional communication strategy on recruitment into a large-scale, multi-centre trial.", "A randomized trial of the impact of telephone and recorded delivery reminders on the response rate to research questionnaires.", "Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.", "Successful recruitment of minorities into clinical trials: The Kick It at Swope project." ]

[ "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.", "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.", "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.", "Psychological theory suggests that participants may be more likely to volunteer to join a clinical trial if they perceive places in the trial are a scarce commodity.\n We conducted a single blind, randomized controlled trial to test recruitment strategies within the larger txt2stop smoking cessation trial. 1862 people who were eligible for the txt2stop trial but had not yet consented to join were randomized to receive either A) a reminder about the txt2stop trial plus a message that there were only 300 places left, or B) a reminder about the trial only. The outcome was the participant's consent to join the txt2stop trial 3days after messages were sent.\n Of 895 participants randomized to the intervention group, 90 (10.1%) had consented to join the txt2stop trial. Of the 967 participants randomized to the control group, 67 (6.9%) had consented to join the txt2stop trial (OR=1.50, 95% CI 1.07-2.12).\n Scarcity messages were an effective way to increase recruitment into the txt2stop trial and could be relevant to other trials.\n Communicating scarcity is an effective way to increase trial recruitment.\n Copyright © 2010 Elsevier Inc. All rights reserved.", "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.", "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.", "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.", "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.", "Ethnic minorities are often underrepresented in clinical trials, and their recruitment can challenge researchers. Developing and communicating effective and efficient recruitment strategies may help researchers enroll more minorities into research studies. Kick It at Swope was a double-blind, randomized trial that evaluated bupropion for smoking cessation among 600 adult African Americans who smoked 10 or more cigarettes a day. Proactive recruitment strategies (in-person appeals by study staff and health care providers) and reactive recruitment strategies (disseminating information that asked people to call a study hotline) were implemented sequentially in an additive fashion over 16 months. Resulting patterns of recruitment are described and the two phases are compared based on their relative effectiveness, efficiency, and cost. More enrollees were recruited in the reactive phase (n=534) than in the proactive phase (n=66). Those recruited in the reactive phase were more likely to be eligible (OR=4.8) and more likely to be enrolled (OR=4.2) than those recruited in the proactive phase. Participants recruited in the reactive phase reported significantly higher levels of education and income, better health, and significantly lower indicators of depression and life hassles, compared with those recruited in the proactive phase. The reactive recruitment phase was less expensive than the proactive recruitment phase (22 US Dollars/enrollee vs. 159 US Dollars/enrollee). Reactive recruitment strategies added to multiple proactive clinic-based recruitment strategies were more effective, more efficient, and less costly than proactive recruitment alone. Close monitoring combined with the use of multiple recruitment methods and flexible recruitment plans can lead to successful, efficient, and low-cost recruitment of minorities into clinical trials." ]

[ "10023787", "9447532", "6502311", "8653433", "9722255", "10681768", "10675427", "12066939", "10509496" ]

[ "Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy.", "Comparative efficacy of exosurf and survanta surfactants on early clinical course of respiratory distress syndrome and complications of prematurity.", "Prevention of bronchopulmonary dysplasia by administration of bovine superoxide dismutase in preterm infants with respiratory distress syndrome.", "Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome.", "Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity.", "[The second phase clinical observation of anti-radiation effect by superoxide dismutase].", "Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group.", "A double-blind randomised controlled trial of continuous oxygen therapy for compromised fetuses.", "Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial." ]

[ "Recent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome (RDS). To investigate whether early (<12 hr) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease (CLD), a randomized, double-blind, controlled trial was conducted in 40 infants (birth weights from 500 to 1,999 gm) who had severe RDS and required mechanical ventilation within 6 hr of birth. All infants received one dose of Survanta before they were randomly assigned to control (saline placebo) or dexamethasone-treated groups (0.5 mg/kg/d for 1 week, then tapered over 3 weeks). Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28. Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment. Among the survivors, 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study. Infants in the treated group had transient hyperglycemia and hypertension. There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage. We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants. To substantiate our result, large randomized controlled trials are needed and warranted.", "To determine the comparative efficacy of Exosurf Neonatal and Survanta surfactants on the early course of respiratory distress syndrome (RDS), arterial blood gases, ventilatory support, outcome morbidity rate, and complications of prematurity and RDS.\n Medical records from 203 premature newborn infants undergoing mechanical ventilation for respiratory distress syndrome, and who received up to four rescue doses of either Exosurf or Survanta, were retrospectively reviewed.\n All groups were comparable for birth weight and gestational age. Although the two randomized groups were similar in severity of RDS based on fraction of inspired oxygen (FIO2) and ventilatory support, a significantly greater improvement in respiratory function as evidenced by FIO2, mean airway pressure, alveolar-arterial partial pressure of oxygen difference, and oxygen index, was observed in the Survanta group from 12 hours (p < 0.05) through 48 hours (p < 0.01). Comparison of outcome morbidity rate by gestational age showed a higher occurrence of retinopathy of prematurity (p < 0.02) among the older infants (28 to 32 weeks) who were treated with Exosurf.\n Survanta exerted a significantly faster response in the early clinical course of RDS compared with Exosurf. However, no difference in the impact on eventual respiratory outcome was observed. We therefore conclude that both surfactants are effective for the treatment of RDS.", "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.", "To study the effect of early postnatal dexamethasone (days 1-3) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome.\n A multicentre, randomised, placebo controlled, blinded study was carried out in 18 neonatal intensive care units in Israel. The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life. The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days, duration of ventilation or oxygen therapy, need for subsequent steroids for established chronic lung disease and incidence of major morbidities.\n The study consisted of 248 infants (dexamethasone n = 132; placebo n = 116). No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants (dexamethasone 44%, placebo 67%; P = 0.001). Gastrointestinal haemorrhage, hypertension, and hyperglycaemia were more common in treated infants, but no life threatening complications, such as gastrointestinal perforation, were encountered.\n These data do no support the routine use of early postnatal steroids, but may justify further study in a selected, high risk group of infants.", "In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD.", "Multiple center randomized controlled double blind clinical trait was conducted to evaluate the anti-radiotherapy effect by SOD (produced by Hunan Biochemical Work) in 159 patients. Injection of 4000U SOD immediately after receiving radiotherapy significantly reduced the occurrence rate of skin, oral mucosal, pelvic visceral and systematic adverse reaction, only the reduction of leukopenia did not reach the statistical significant level. No adverse effect of SOD injection was observed. The results suggest that SOD is a safe and effective agent to attenuate the radiotherapy reactions.", "Inhaled nitric oxide improves gas exchange in neonates, but the efficacy of low-dose inhaled nitric oxide in reducing the need for extracorporeal membrane oxygenation has not been established.\n We conducted a clinical trial to determine whether low-dose inhaled nitric oxide would reduce the use of extracorporeal membrane oxygenation in neonates with pulmonary hypertension who were born after 34 weeks' gestation, were 4 days old or younger, required assisted ventilation, and had hypoxemic respiratory failure as defined by an oxygenation index of 25 or higher. The neonates who received nitric oxide were treated with 20 ppm for a maximum of 24 hours, followed by 5 ppm for no more than 96 hours. The primary end point of the study was the use of extracorporeal membrane oxygenation.\n Of 248 neonates enrolled, 126 were randomly assigned to the nitric oxide group and 122 to the control group. Extracorporeal membrane oxygenation was used in 78 neonates in the control group (64 percent) and in 48 neonates in the nitric oxide group (38 percent) (P=0.001). The 30-day mortality rate in the two groups was similar (8 percent in the control group and 7 percent in the nitric oxide group). Chronic lung disease developed less often in neonates treated with nitric oxide than in those in the control group (7 percent vs. 20 percent, P=0.02). The efficacy of nitric oxide was independent of the base-line oxygenation index and the primary pulmonary diagnosis.\n Inhaled nitric oxide reduces the extent to which extracorporeal membrane oxygenation is needed in neonates with hypoxemic respiratory failure and pulmonary hypertension.", "To investigate the effect of chronic oxygen therapy in fetuses with absent end diastolic flow in the umbilical artery assessed by doppler analysis at 24-30 weeks of gestation.\n A double-blind, randomised control trial was performed with patients blindly allocated to receive humidified oxygen or humidified air.\n A tertiary referral hospital in South Africa.\n Thirty-two women who presented between 24 and 30 weeks of gestation with a confirmed finding of absent end diastolic flow in the umbilical artery.\n After randomisation patients were allocated to receive a 40% mixture of humidified oxygen or humidified air from uniform coloured gas cylinders which were marked either 'a' or 'b' All women received betamethasone from 27 weeks of gestation on a weekly basis. Cardiotocographs were used from 28 weeks of gestation; after 28 weeks of gestation an amniocentesis was considered to confirm fetal maturity. Women were expected to breath the allocated gas continuously apart from meals and visits to the toilet.\n Survival of the fetus was the main outcome measure with secondary outcome measures documenting improvement in the fetal condition in utero.\n There were 16 women randomised to receive oxygen and 16 to receive air. There were nine survivors in the oxygen group (56.3%) and six in the air group (37.5%) (relative risk 1.5, 95% confidence interval 0.7-3.2). There was a nonsignificant increase in mean birthweight in the oxygen group (858.3 grammes vs 774.4 grammes) and a nonsignificant increase in mean duration of treatment in the oxygen group (12.8 days vs 10.4 days).\n This study did not demonstrate that chronic oxygen therapy provides any benefits to compromised fetuses between 24 and 30 weeks of gestation. Larger studies with sufficient power are necessary to assess whether oxygen therapy can reduce perinatal mortality by a clinically useful amount in this group of patients.", "Inhaled nitric oxide improves oxygenation and lessens the need for extracorporeal-membrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease.\n We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age < or = 34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age.\n The two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0.03). Survival at discharge was 52% in the inhaled-nitric-oxide group and 47% in controls (p=0.65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%).\n Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury." ]

[ "10767227", "8162979", "18399862", "12683707", "8620707", "10714421", "19075206", "19272084", "8162723" ]

[ "Long-term effects of outpatient rehabilitation of COPD: A randomized trial.", "Quality of life in patients with chronic obstructive pulmonary disease improves after rehabilitation at home.", "Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis.", "Pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.", "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.", "Rehabilitation of patients with chronic obstructive pulmonary disease. Exercise twice a week is not sufficient!", "Effects of home-based pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial.", "Does early pulmonary rehabilitation reduce acute health-care utilization in COPD patients admitted with an exacerbation? A randomized controlled study.", "The effect of comprehensive outpatient pulmonary rehabilitation on dyspnea." ]

[ "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 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.", "Although pulmonary rehabilitation is effective for patients with COPD, its efficacy in patients with IPF is unknown. The purpose of this study was to evaluate the effects of pulmonary rehabilitation in IPF.\n Thirty patients diagnosed with IPF, according to the consensus statement, were randomly assigned to the rehabilitation group or the control group. The pulmonary rehabilitation mainly consisted of a 10-week programme of exercise training. Pulmonary function, blood gas analysis, 6MWD, dyspnoea rating with the baseline dyspnoea index and health-related quality of life score on the St George's Respiratory Questionnaire were evaluated at baseline and after the programme.\n Assessment of efficacy was carried out on 13 patients who completed the programme and 15 patients in the control group. There were no significant effects of the programme on measures of pulmonary function, values of arterial blood gas analysis or dyspnoea rating. Although there were some differences in the baseline 6MWD and total health-related quality of life score which were not statistically significant, marked improvements were observed in the 6MWD (mean difference 46.3 m (95% CI: 8.3-84.4), P < 0.05) and the total health-related quality of life score (-6.1 (95% CI: -11.7 to -0.5), P < 0.05).\n Pulmonary rehabilitation improves both exercise capacity and health-related quality of life in patients with IPF.", "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.", "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.", "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.", "Home-based rehabilitation is a promising approach to improve access to pulmonary rehabilitation.\n To assess whether self-monitored, home-based rehabilitation is as effective as outpatient, hospital-based rehabilitation in patients with chronic obstructive pulmonary disease (COPD).\n Randomized, multicenter, noninferiority trial.\n 10 academic and community medical centers in Canada.\n 252 patients with moderate to severe COPD.\n After a 4-week education program, patients took part in home-based rehabilitation or outpatient, hospital-based rehabilitation for 8 weeks. They were followed for 40 weeks to complete the 1-year study.\n The primary outcome was the change in Chronic Respiratory Questionnaire dyspnea subscale score at 1 year. The primary analysis took a modified intention-to-treat approach by using all patients who provided data at the specified follow-up time, regardless of their level of adherence. The analysis used regression modeling that adjusted for the effects of center, sex, and baseline level. All differences were computed as home intervention minus outpatient intervention.\n Both interventions produced similar improvements in the Chronic Respiratory Questionnaire dyspnea subscale at 1 year: improvement in dyspnea of 0.62 (95% CI, 0.43 to 0.80) units in the home intervention (n = 107) and 0.46 (CI, 0.28 to 0.64) units in the outpatient intervention (n = 109). The difference between the 2 treatments at 1 year was small and clinically unimportant. The 95% CI of the difference did not exceed the prespecified noninferiority margin of 0.5: difference in dyspnea score of 0.16 (CI, -0.08 to 0.40). Most adverse events were related to COPD exacerbations. No serious adverse event was considered to be related to the study intervention.\n The contribution of the educational program to the improvement in health status and exercise tolerance cannot be ascertained.\n Home rehabilitation is a useful, equivalent alternative to outpatient rehabilitation in patients with COPD.", "In COPD, hospital admissions and readmissions account for the majority of health-care costs. The aim of this prospective randomized controlled study was to determine if early pulmonary rehabilitation, commenced as an inpatient and continued after discharge, reduced acute health-care utilization.\n Consecutive COPD patients (n = 397), admitted with an exacerbation, were screened: 228 satisfied the eligibility criteria, of whom 97 consented to randomization to rehabilitation or usual care. Both intention-to-treat and per-protocol analyses are reported with adherence being defined a priori as participation in at least 75% of rehabilitation sessions.\n The participants were elderly with severe impairment of pulmonary function, poor health-related quality of life and high COPD-related morbidity. The rehabilitation group demonstrated a 23% (95% CI: 11-36%) risk of readmission at 3 months, with attendees having a 16% (95% CI: 0-32%) risk compared with 32% (95% CI: 19-45%) for usual care. These differences were not significant. There were a total of 79 COPD-related readmission days (1.7 per patient, 95% CI: 0.6-2.7, P = 0.19) in the rehabilitation group, compared with 25 (1.3 per patient, 95% CI: 0-3.1, P = 0.17) for the attendees and 209 (4.2 per patient, 95% CI: 1.7-6.7) for usual care. The BMI, airflow obstruction, dyspnoea and exercise capacity index showed a non-significant trend to greater improvement among attendees compared with those receiving usual care (5.5 (2.3) and 5.6 (2.7) at baseline, improving to 3.7 (1.9) and 4.5 (2.5), respectively, at 3 months). No adverse effects were identified.\n Early inpatient-outpatient rehabilitation for COPD patients admitted with an exacerbation was feasible and safe, and was associated with a non-significant trend towards reduced acute health-care utilization.", "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." ]

[ "2343859", "2705601", "9829873", "9243440", "2081243", "15972931", "18174120", "10330737", "16085200" ]

[ "Effectiveness of various mailing strategies among nonrespondents in a prospective cohort study.", "Increasing response rates in physicians' mail surveys: an experimental study.", "Controlled trial of the effect of length, incentives, and follow-up techniques on response to a mailed questionnaire.", "A randomized trial of the impact of telephone and recorded delivery reminders on the response rate to research questionnaires.", "Effects of mailing strategies on response rate, response time, and cost in a questionnaire study among nurses.", "Increasing response to mailed questionnaires by including a pencil/pen.", "No increase in response rate by adding a web response option to a postal population survey: a randomized trial.", "Primer postcard improves postal survey response rates.", "Initial nonresponders had an increased response rate after repeated questionnaire mailings." ]

[ "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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." ]

[ "11978259", "11978262", "1846723", "2841662", "15531671", "8112194", "20851308", "9093546", "2005733" ]

[ "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.", "Effects on serum lipids of adding instant oats to usual American diets.", "Serum lipid response to a fat-modified, oatmeal-enhanced diet.", "Changes in whole-grain, bran, and cereal fiber consumption in relation to 8-y weight gain among men.", "Long-term comparison of three dietary prescriptions in the treatment of NIDDM.", "Randomized, controlled trial promotes physical activity and reduces consumption of sweets and sodium among overweight and obese adults.", "A long-term study on the effect of spontaneous consumption of reduced fat products as part of a normal diet on indicators of health.", "The hypocholesterolemic effects of beta-glucan in oatmeal and oat bran. A dose-controlled study." ]

[ "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.", "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.", "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.", "Epidemiologic studies that directly examine changes in whole-grain consumption in relation to weight gain are sparse, and characterization of this association has been obscured by methodologic inconsistencies in the assessment of whole grains.\n We aimed to ascertain the associations between changes in new quantitative estimates of whole-grain intake and 8-y weight gain among US men.\n The study was conducted in a prospective cohort of 27 082 men aged 40-75 y at baseline in 1986. Data on lifestyle factors were obtained periodically by using self-reported questionnaires, and participants measured and reported their body weight in 1986 and 1994.\n In multivariate analyses, an increase in whole-grain intake was inversely associated with long-term weight gain (P for trend < 0.0001). A dose-response relation was observed, and for every 40-g/d increment in whole-grain intake from all foods, weight gain was reduced by 0.49 kg. Bran that was added to the diet or obtained from fortified-grain foods further reduced the risk of weight gain (P for trend = 0.01), and, for every 20 g/d increase in intake, weight gain was reduced by 0.36 kg. Changes in cereal and fruit fiber were inversely related to weight gain. No associations were observed between changes in refined-grain or added germ consumption and body weight.\n The increased consumption of whole grains was inversely related to weight gain, and the associations persisted after changes in added bran or fiber intakes were accounted for. This suggests that additional components in whole grains may contribute to favorable metabolic alterations that may reduce long-term weight gain.", "To compare three sets of dietary guidelines for the treatment of non-insulin-dependent diabetes (NIDDM) in free-living individuals and to observe the effects on metabolic control over an 18-month period.\n Seventy volunteer subjects with NIDDM were randomly assigned to one of three diets, a weight-management diet, a high-carbohydrate/fiber diet, or a modified-lipid diet and followed for 18 months. Nutrient intakes, weight, blood lipids, and glycemic control were measured.\n In all diet groups, glycated hemoglobin (HbA1) fell significantly before diet intervention began, remaining lower throughout the study and at follow-up 9 months later. Low-density lipoprotein (LDL) cholesterol showed a sustained fall in all groups after diet intervention. Apart from transient changes in high-density lipoprotein (HDL) cholesterol and triglyceride (TG) in the diet groups with the higher carbohydrate intake, no lasting differences were found between the three diet groups.\n In the long term, there were few differences in the outcome of the three dietary prescriptions. Even with intensive instruction, participants found it difficult to meet recommended nutrient intakes; however, specific dietary advice did result in an improvement in LDL cholesterol. Adverse changes in HDL cholesterol and TG because of diet intervention were transient. The significant improvement in glycemic control during the recruitment phase may have been the result of participants' previous dietary knowledge and the increased attention that they received during the intervention.", "The present study sought to assess the impact of an intervention to reduce weight and control risk factors of noncommunicable chronic diseases in overweight or obese adults who are users of primary and secondary healthcare units of the public health system of Pelotas, Brazil. We hypothesized that individuals who received an educational intervention regarding how to lose weight and prevent other noncommunicable chronic disease risk factors through nutrition would lose weight and acquire active habits during leisure time more frequently than individuals under regular care. Two hundred forty-one participants from the Nutrition Outpatient Clinic of the Medical Teaching Hospital of the Federal University of Pelotas, Brazil, aged 20 years or older and classified as overweight or obese were randomly allocated to either the intervention group (IG; n = 120) or control group (CG; n = 121). The IG received individualized nutritional care for 6 months, and the CG received individualized usual care of the health services. Intention-to-treat analyses showed that at 6 months, mean fasting glycemia and daily consumption of sweet foods and sodium were reduced, and the time spent on physical leisure activity was increased in IG. Analysis of adherence to the protocol of the study revealed that individuals from IG had lost more in body weight, waist circumference, and fasting glucose compared to the CG. Leisure time physical activity increased in IG. Individuals adhered equally to the dietetic recommendations, irrespective of the nutrition approach that was used.\n Copyright © 2010 Elsevier Inc. All rights reserved.", "The growing public concern with the adverse effects on health of a high fat intake has led to a proliferation on the market of reduced fat products. However, no consensus exists on the effectivity of reduced fat products to decrease energy intake. The studies that have investigated this topic have included small numbers of subjects, studied under laboratory conditions and over a relatively short period of time. Therefore, we have executed a long-term study in which volunteers had free access to both reduced fat, commercially available products in the laboratory as well as to products obtained from regular shops. We here report the feasibility of such a type of study and the effects of consumption of reduced fat products on blood levels of cholesterol, haemostasis variables, antioxidants and parameters of the immune system. The study was a multicentre parallel comparison trial of six months (so-called MSFAT-study). 241 volunteers received either reduced fat products or full-fat products and the products were clearly labelled as such. Two months before the start of the study, a 1 month adaptation period was executed to optimize the experimental procedures. Food intake was recorded before the start of the adaptation period and 2-4 weeks, 3 months and 6 months after the start of the study. Blood samples were taken before, after 2, 4 and 6 months of the study. In addition, a selection of the reduced fat and full-fat products was sensorically evaluated three times during the study by a subgroup of the volunteers. 220 volunteers completed the study. The reduced fat group consumed on average 46% less fat from the so-called MSFAT-products obtained from the shop at the laboratory than the control group and consumption of these MSFAT-products did not decrease in either of the groups during the time course of the study. The palatability of the reduced fat and full-fat products was similar and as expected, the perceived fattiness of the full-fat products was higher than that of the reduced fat products. No effects were found on blood levels of cholesterol, haemostasis variables, parameters of antioxidant status and immune system characteristics. In conclusion, the experimental manipulation of the fat content of the diet that was achieved and that remained stable throughout the 6 months of the study indicates that this type of set-up is feasible to assess the effects of long-term nutritional intervention in large groups of volunteers under semi-controlled conditions. The regular use of reduced fat products did not positively but also not adversely affect blood cholesterol levels, antioxidant status, haemostasis factors and the body's immune system.", "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." ]

[ "2179650", "16330624", "19755362", "17976288", "9217619", "7496238", "10675118", "10320115", "11593835" ]

[ "Improving physicians' recognition and treatment of depression in general medical care. Results from a randomized clinical trial.", "Systematic detection and multidisciplinary care of depression in older medical inpatients: a randomized trial.", "Case management for depression by health care assistants in small primary care practices: a cluster randomized trial.", "Graduate mental health worker case management of depression in UK primary care: a pilot study.", "A randomized trial of office-based screening for common problems in older persons.", "Twelve month outcome of depression in general practice: does detection or disclosure make a difference?", "Effects of a clinical-practice guideline and practice-based education on detection and outcome of depression in primary care: Hampshire Depression Project randomised controlled trial.", "Case-finding for depression in primary care: a randomized trial.", "Randomised controlled trial of tailored strategies to implement guidelines for the management of patients with depression in general practice." ]

[ "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.", "Major depression is a frequent and serious disorder in older medical inpatients. Because the condition goes undetected and untreated in most of these patients, we conducted a randomized clinical trial to evaluate the effectiveness of a strategy of systematic detection and multidisciplinary treatment of depression in this population.\n Consecutive patients aged 65 years or more admitted to general medical services in a primary care hospital between October 1999 and November 2002 were screened for depression with the Diagnostic Interview Schedule (DIS) within 48 hours after admission. Patients found to have major depression were randomly allocated to receive the intervention or usual care. The intervention involved consultation and treatment by a psychiatrist and follow-up by a research nurse and the patient's family physician. Research assistants, blind to group allocation, collected data from the patients at enrollment and at 3 and 6 months later using the Hamilton Depression Rating Scale (HAMD), the Medical Outcomes 36-item Short Form (SF-36), the DIS, the Mini-Mental State Examination (MMSE), the Older Americans Resources and Services (OARS) questionnaire to assess basic and instrumental activities of daily living (OARS-ADL and OARS-IADL) and the Rating Scale for Side Effects. Data on the severity of illness, length of hospital stay, health services and medication use, mortality and process of care were also collected. The primary outcome measures were the HAMD and SF-36.\n Of 1500 eligible patients who were screened, 157 were found to have major depression and consented to participate (78 in the intervention group and 79 in the usual care group). At randomization, there were no clinically or statistically significant differences between the 2 groups. Sixty-four patients completed follow-up to 6 months, 57 withdrew, and 36 died. At 6 months, there were no clinically or statistically significant differences the 2 groups in HAMD or SF-36 scores or any of the secondary outcome measures.\n We were unable to demonstrate that systematic detection and multidisciplinary care of depression was more beneficial than usual care for elderly medical inpatients.", "Case management by health care assistants in small primary care practices provides unclear benefit for improving depression symptoms.\n To determine whether case management provided by health care assistants in small primary care practices is more effective than usual care in improving depression symptoms and process of care for patients with major depression.\n Cluster randomized, controlled trial. A central automated system generated the randomization scheme, which was stratified by urban and rural practices; allocation sequence was concealed until groups were assigned.\n 74 small primary care practices in Germany from April 2005 to September 2007.\n 626 patients age 18 to 80 years with major depression.\n Structured telephone interview to monitor depression symptoms and support for adherence to medication, with feedback to the family physician.\n Depression symptoms at 12 months, as measured by the Patient Health Questionnaire-9 (PHQ-9); secondary outcomes were patient assessment of chronic illness care, adherence to medication, and quality of life.\n A total of 310 patients were randomly assigned to case management and 316 to usual care. At 12 months, 249 intervention recipients and 278 control patients were assessed; 555 patients were included in a modified intention-to-treat-analysis (267 intervention recipients vs. 288 control patients). Compared with control patients, intervention recipients had lower mean PHQ-9 values in depression symptoms (-1.41 [95% CI, -2.49 to -0.33]; P = 0.014), more favorable assessments of care (3.41 vs. 3.11; P = 0.011), and increased treatment adherence (2.70 vs. 2.53; P = 0.042). Quality-of-life scores did not differ between groups.\n Patients, health care assistants, family physicians, and researchers were not blinded to group assignment, and 12-month follow-up of patients was incomplete.\n Case management provided by primary care practice-based health care assistants may reduce depression symptoms and improve process of care for patients with major depression more than usual care.\n German Ministry of Education and Research.", "Based on data from large multicentre US trials, the National Institute for Health and Clinical Excellence (NICE) is advocating a stepped-care model for the management of depression, with 'case management' or 'collaborative care' for selected patients in primary care.\n To conduct a pilot study examining the use of graduate mental health workers case managing depressed primary care NHS patients.\n A randomised controlled trial comparing usual GP care with or without case management over 16 weeks of acute antidepressant drug treatment.\n Three primary care practices in the North East of England.\n Patients with depression, aged 18-65 years, who had failed to adequately respond to antidepressant treatment, were randomised to the two treatments. Assessments were made at baseline, 12, and 24 weeks using a combination of observer and self ratings.\n Randomisation of 62 patients required screening of 1073 potential patients. There was little difference in outcome between the two treatment arms but a gradual improvement in symptoms over time was seen. Client satisfaction was assessed as high across both treatments.\n While this pilot study confirmed the integrity of the study protocol and the suitability of the outcome measures and randomisation procedure, it raises questions regarding the practicality of recruitment and feasibility of the intervention. It would be crucial to address these issues prior to the implementation of a large multi-centre randomised controlled trial.", "To test the effectiveness of a 10-minute office-staff administered screen to evaluate malnutrition/weight loss, visual impairment, hearing loss, cognitive impairment, urinary incontinence, depression, physical limitations, and reduced leg mobility among older persons seen in office practice. This screen was coupled with clinical summaries to assist the physician in further evaluating and managing the screen-included problems.\n Twenty-six community-based office practices of internists and family physicians in Los Angeles were randomized to intervention or control groups. Two hundred and sixty-one patients aged > or = 70 years and seeing these physicians for a new visit or a physical examination participated in the study. At the enrollment visit intervention group patients were administered the screening measure and their physicians were given the pertinent clinical summaries. Outcome measures were detection of, and intervention for conditions screened, and health status 6 months after the intervention.\n Hearing loss was both more commonly detected (40% intervention versus 28% control) and further evaluated (29% versus 16%) by physicians in the intervention group (P < 0.05). No other differences in the frequency of problem detection or intervention were noted between groups. Six months after the intervention no differences were noted in health status between groups.\n A brief measure to screen for common conditions in older persons was associated with more frequent detection and follow-up assessment of hearing loss. Although the measure was well accepted by physicians and their staffs, it did not appear to affect detection and intervention in regard to the other screen-included conditions, or health status at 6 months.", "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.", "Depression is a major individual and public-health burden throughout the world and is managed mainly in primary care. The most effective strategy to reduce this burden has been believed to be education of primary-care practitioners. We tested this assumption by assessing the effectiveness of an educational programme based on a clinical-practice guideline in improving the recognition and outcome of primary-care depression.\n We carried out a randomised controlled trial in a representative sample of 60 primary-care practices (26% of the total) in an English health district. Education was delivered to practice teams and quality tested by feedback from participants and expert raters. The primary endpoints were recognition of depression, defined by the hospital anxiety and depression (HAD) scale, and clinical improvement. Analysis was by intention to treat.\n The education was well received by participants, 80% of whom thought it would change their management of patients with depression. 21409 patients were screened, of whom 4192 were classified as depressed by the HAD scale. The sensitivity of physicians to depressive symptoms was 39% in the intervention group and 36% in the control group after education (odds ratio 1.2 [95% CI 0.88-1.61]). The outcome of depressed patients as a whole at 6 weeks or 6 months after the assessment did not significantly improve.\n Although well received, this in-practice programme, which was designed to convey the current consensus on best practice for the care of depression, did not deliver improvements in recognition of or recovery from depression.", "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.", "Various methods are available for implementing change in the clinical behaviour of general practitioners (GPs). Although passive dissemination of information is generally ineffective, other methods can be variably effective. Few studies have investigated the impact of tailored methods.\n To determine whether methods tailored to overcome obstacles to change using psychological theories are more effective than dissemination alone in the implementation of guidelines for depression among GPs.\n Randomised controlled trial.\n Sixty general practices in England; 30 GPs in the control group, 34 in the intervention group.\n Practitioners identified patients presenting with depression before and after the implementation of guidelines (control group n = 192 in the first data collection, n = 181 in the second; intervention group n = 210 in the first data collection and n = 197 in the second). The main outcome measures were: record of adherence to guideline recommendations in clinical records; proportion of patients with Beck Depression Inventory (BDI) score less than 11 at 16 weeks after diagnosis.\n In comparison with the control group, in the group of GPs receiving tailored implementation, there were increases in the proportions of patients assessed for suicide risk. In the intervention group, the proportion of patients with BDI scores of less than 11 at 16 weeks increased.\n Obstacles to implementation can be identified and strategies tailored to address them. The findings indicate a new approach for research to understand and develop methods of implementation." ]

[ "10028979", "3191758", "1896416", "18947861", "11152840", "10391261", "20638899", "2407200", "7881929" ]

[ "Transmyocardial laser revascularisation in patients with refractory angina: a randomised controlled trial.", "Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients.", "Randomized clinical trial of transabdominal versus transcervical chorionic villus sampling methods.", "Total laparoscopic hysterectomy versus abdominal hysterectomy with lymphadenectomy for early-stage endometrial cancer: a prospective randomized study.", "Impact of presentation of research results on likelihood of prescribing medications to patients with left ventricular dysfunction.", "Holmium:YAG laser transmyocardial revascularization relieves angina and improves functional status.", "Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE): a randomised trial.", "Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation. Ventriculomegaly Trial Group.", "Preoperative transcatheter arterial chemoembolization for resectable large hepatocellular carcinoma: a reappraisal." ]

[ "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.", "Survivors of high-risk surgical operations were previously observed to have significantly higher mean CI, DO2, and VO2 than nonsurvivors. The hypothesis was proposed that increased CI and DO2 are circulatory compensations for increased postoperative metabolism. We tested this hypothesis in two series. In series 1, prospectively allocated by services, mortality and morbidity of the control group were significantly greater than those of the protocol group. In series 2, patients who fulfilled previously defined high-risk criteria were preoperatively randomized to one of three monitoring/treatment groups: CVP-control group, PA-control group and PA-protocol group. Postoperative mortalities in the CVP-control and PA-control groups were not statistically significantly different, but PA-protocol group mortality was significantly reduced compared with its control group. The PA-protocol group had reduced complications, duration of hospitalization, duration in ICU, and mechanical ventilation, and reduced costs when the PA catheter was placed preoperatively and used to augment circulatory responses.", "The relative advantages and disadvantages of transabdominal (TA) and transcervical (TC) chorionic villus sampling (CVS) in terms of fetal risks and efficacy were evaluated in a clinical trial conducted on 1194 women randomized at 7-12 weeks' gestation. The results of the study indicate that, if any, the relative risk of fetal loss following either procedure is less than double that of the alternative technique when performed by a skilled operator. Overall, the fetal loss rate (spontaneous abortions following randomization, terminations of pregnancy, and perinatal deaths) is 16.5 and 15.5 per cent, respectively, among women allocated to TA- and TC-CVS. The two procedures are equally effective, although TA-CVS is associated with a significantly lower rate of repeat device insertions; on the other hand, a higher weight of chorionic tissue is obtained, on average, with TC-CVS. Bleeding is more common following TC-CVS, while peritoneal reaction developed only after TA-CVS. No diagnostic problems specifically related to one sampling technique were identified.", "The aim of this study was to compare, in a series of 159 women the feasibility, safety and morbidity of total laparoscopic hysterectomy (LPS) and abdominal hysterectomy with lymphadenectomy (LPT) for early-stage endometrial cancer and to assess disease-free survival and recurrence rate.\n 159 patients with clinical stage I endometrial cancer were enrolled in a prospective randomized trial and treated with LPS or LPT approach. The para-aortic lymphadenectomy was performed in all cases with positive pelvic lymph nodes discovered at frozen section evaluation, in patients with poorly differentiated tumors with myometrial invasion greater than 50% (ICG3), and non-endometrioid carcinomas.\n The mean operative time was 136 min+/-31 (95% CI 118-181) in the LPS group and 123 min+/-29 (95% CI 111-198) in the LPT group (P<0.01). The mean blood loss was 50 ml+/-12 in the LPS group (95% CI 20-90) and 145 ml+/-35 in the LPT group (95% CI 60-255) (P<0.01). The mean length of hospital stay was 5.1+/-1.2 in the LPT group (95% CI 1-7) and 2.1+/-0.5 in the LPS group (95% CI 1-5) (P<0.01).\n Laparoscopy is a suitable procedure for the treatment of patients with early endometrial cancer and may offer the potential benefits of decreased discomfort with decreased convalescence time without compromising the degree of oncological radicality required; however, it does not seem to modify the disease-free survival and the overall survival, although multicenter randomized trials and long-term follow-up are required to evaluate the overall oncologic outcomes of this procedure.", "This study was conducted to evaluate willingness to prescribe medication based on identical data presented in different outcome terms to health professionals of varied discipline, geographic location, and level of training. Cross-sectional survey using a self-administered questionnaire was performed in 400 health professionals (physicians, pharmacists, physicians-in-training, and pharmacy students) in the United States and Europe. Data reflecting a clinical trial were presented in 6 outcome terms: 3 terms describing identical mortality (relative risk reduction, absolute risk reduction, and number of patients needed to be treated to prevent 1 death); and 3 distractors (increased life expectancy, decreased hospitalization rate, and decreased cost). Willingness to prescribe and rank order of medication preference assuming willingness to prescribe were measured. The results of the study showed that willingness to prescribe and first choice preference were significantly greater when study results were presented as relative risk reduction than when identical mortality data were presented as absolute risk reduction or number of patients needed to be treated to avoid 1 death (p <0.001). Increase in life expectancy was the most influential distractor. In conclusion, this study, performed in the era of \"evidence-based medicine,\" demonstrates that the method of reporting research trial results has significant influence on health professionals' willingness to prescribe. The high numerical value of relative risk reduction and the concrete and tangible quality of increased life expectancy exert greater influence on health professionals than other standard outcome terms.", "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.", "This two-stage randomised controlled trial, comparing total laparoscopic hysterectomy (TLH) with total abdominal hysterectomy (TAH) for stage I endometrial cancer (LACE), began in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved quality of life (QoL) up to 6 months after surgery compared with TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Here, we present the results of stage 1.\n Between Oct 7, 2005, and April 16, 2008, 361 participants were enrolled in the QoL substudy at 19 centres across Australia, New Zealand, and Hong Kong; 332 completed the QoL analysis. Randomisation was done centrally and independently from other study procedures via a computer-generated, web-based system (providing concealment of the next assigned treatment), using stratified permuted blocks of three and six patients. Patients with histologically confirmed stage I endometrioid adenocarcinoma and Eastern Cooperative Oncology Group performance status less than 2 were randomly assigned to TLH (n=190) or TAH (n=142), stratified by histological grade and study centre. Patients and study personnel were not masked to treatment assignment. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery, using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between groups in QoL change from baseline at early and late timepoints (a 5% difference was considered clinically significant). Analysis was done according to the intention-to-treat principle. Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. The LACE trial is registered with ClinicalTrials.gov, number NCT00096408.\n Eight of 332 patients (2.4%) had treatment conversion-seven from TLH to TAH and one from TAH to TLH (patient preference). In the early phase of recovery, patients who had TLH reported significantly greater improvement in QoL from baseline compared with those who had TAH, in all subscales apart from emotional and social wellbeing. Improvements in QoL up to 6 months after surgery continued to favour TLH, except in the emotional and social wellbeing measures of FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Operating time was significantly longer in the TLH group (138 min [SD 43]) than in the TAH group (109 min [34]; p=0.001). Although the proportion of intraoperative adverse events was similar between groups (TAH eight of 142 [5.6%] vs TLH 14 of 190 [7.4%]; p=0.53); postoperatively, twice as many patients in the TAH group experienced adverse events of grade 3 or higher (33 of 142 [23.2%] vs 22 of 190 [11.6%] in the TLH group; p=0.004). Postoperative serious adverse events occurred more in the TAH group (27 of 142 [19.0%]) than in the TLH group (16 of 190 [7.9%]; p=0.002).\n QoL improvements from baseline during early and later phases of recovery, and the adverse event profile, favour TLH compared with TAH for treatment of stage I endometrial cancer.\n Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council Western Australia; NHMRC project grant 456110; Cancer Australia project grant 631523; The Women and Infants Research Foundation, Western Australia; Royal Brisbane and Women's Hospital Foundation; Wesley Research Institute; Gallipoli Research Foundation; Gynetech; TYCO Healthcare, Australia; Johnson and Johnson Medical, Australia; Hunter New England Centre for Gynaecological Cancer; Genesis Oncology Trust; and Smart Health Research Grant QLD Health.\n 2010 Elsevier Ltd. All rights reserved.", "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.", "Transcatheter arterial chemoembolization (TACE) improves the treatment of hepatocellular carcinoma (HCC) by causing tumour necrosis and shrinkage. Fifty-two patients with resectable large HCC (defined as a maximal tumour diameter of 10 cm or more) were prospectively randomized into two groups: group 1 comprised 24 patients who had 1-5 sessions of TACE before operation; group 2 consisted of the other 28 patients, on whom surgery was performed without delay. Tumour volume was reduced to a mean (s.d.) of 42.8 (15.3) per cent in 16 patients in group 1, but remained unchanged in four and increased in size in a further four. Patients in group 1 had a slightly longer operating time (5.5 versus 4.6 h, P = 0.09), a higher rate of concomitant resection of adjacent organs (58 versus 25 per cent, P = 0.03) and a higher rate of histological invasion to these organs (33 versus 4 per cent, P = 0.01). No difference was found between the two groups in operative blood loss, operative morbidity and mortality rates, and pathological staging. The disease-free survival rate in the two groups was similar, but the incidence of extrahepatic cancer recurrence was higher in group 1 (57 versus 23 per cent, P = 0.03). The actuarial survival rate was also significantly worse in group 1 when determined from the time of detection of the tumour (P = 0.03) or from operation (P = 0.01). It is concluded that preoperative TACE for resectable large HCC should be avoided because it does not provide complete necrosis in large tumours and results in delayed surgery and difficulty in the treatment of recurrent lesions, without any benefit." ]

[ "20508185", "22275463", "19692788", "17167194", "15890990", "21840917", "18633001", "12601321", "19118130" ]

[ "Effectiveness of virtual reality using Wii gaming technology in stroke rehabilitation: a pilot randomized clinical trial and proof of principle.", "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 training for stroke rehabilitation.", "Virtual reality-induced cortical reorganization and associated locomotor recovery in chronic stroke: an experimenter-blind randomized study.", "Effects of robot-assisted upper limb rehabilitation on daily function and real-world arm activity in patients with chronic stroke: a randomized controlled trial.", "Satisfaction with care in post-stroke patients undergoing a telerehabilitation programme at home.", "Vestibular rehabilitation: useful but not universally so.", "Effects of constraint-induced therapy versus bilateral arm training on motor performance, daily functions, and quality of life in stroke survivors." ]

[ "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 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.", "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.", "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.", "To compare the outcome of robot-assisted therapy with dose-matched active control therapy by using accelerometers to study functional recovery in chronic stroke patients.\n Prospective, randomized, controlled trial. Setting: Stroke units in three medical centres. Subjects: Twenty patients post stroke for a mean of 22 months. Intervention: Robot-assisted therapy (n = 10) or dose-matched active control therapy (n = 10). All patients received either of these two therapies for 90-105 minutes each day, 5 days per week, for four weeks.\n Outcome measures included arm activity ratio (the ratio of mean activity between the impaired and unimpaired arm) and scores on the Fugl-Meyer Assessment Scale, Functional Independence Measure, Motor Activity Log and ABILHAND questionnaire.\n The robot-assisted therapy group significantly increased motor function, hemiplegic arm activity and bilateral arm coordination (Fugl-Meyer Assessment Scale: 51.20 ± 8.82, P = 0.002; mean arm activity ratio: 0.76 ± 0.10, P = 0.026; ABILHAND questionnaire: 1.24 ± 0.28, P = 0.043) compared with the dose-matched active control group (Fugl-Meyer Assessment Scale: 40.90 ± 13.14; mean arm movement ratio: 0.69 ± 0.11; ABILHAND questionnaire: 0.95 ± 0.43).\n Symmetrical and bilateral robotic practice, combined with functional task training, can significantly improve motor function, arm activity, and self-perceived bilateral arm ability in patients late after stroke.", "We conducted a pilot telerehabilitation study with post-stroke patients with arm motor impairment. We compared the degree of satisfaction of patients undergoing a virtual reality (VR) therapy programme at home (Tele-VR group) to satisfaction experienced by those undergoing the same VR therapy in a hospital setting (VR-group). The rehabilitation equipment used a 3D motion tracking system to create a virtual environment in which the patient's movement was represented. In tele-therapy, the patient equipment was installed in their homes, connected to the hospital by four ISDN lines at a total bandwidth of 512 kbit/s. Rehabilitation data were transmitted via one line and videoconferencing via the other three. Ten patients with mild to intermediate arm motor impairment due to an ischaemic stroke, were randomized into VR or Tele-VR groups. A questionnaire was used at the end of treatment to measure each patient's degree of satisfaction. Tele-VR treated patients showed median values equal to or higher than the VR group patients in all 12 items investigated, except one. In motor performance, the Tele-VR group improved significantly (P < or = 0.05), while the VR group showed no significant change. Patients assigned to the Tele-VR group were able to engage in therapy at home and the videoconferencing system ensured a good relationship between the patient and the physical therapist whose physical proximity was not required.", "Although vestibular rehabilitation (VR) is gaining popularity, few data support its utility in improving locomotor stability, and no good predictors exist of whom will benefit most.\n A double-blind, placebo-controlled randomized trial of vestibular rehabilitation was conducted at a large tertiary care hospital on 124 patients (59 +/- 18 years old) with unilateral (n = 51) or bilateral (n = 73) vestibular hypofunction, of whom 86 completed a 12-week intervention. Of these 86, 27 returned for long-term (1-year) follow-up testing. The primary outcome measure was locomotor stability.\n Group A (6 weeks of VR) significantly (P < 0.01) increased their gait velocity and stability compared with group B (6 weeks of strengthening exercise), but there was a smaller difference (P = 0.05) between groups at 12 weeks, when both had had VR; there were no group differences at 1 year. Of the 86 who completed the intervention, 52 (61%) had clear locomotor gains.\n VR is helpful for most patients in providing locomotor stability, but further work is needed to determine the factors that prevent VR from being effective for all patients with vestibulopathy.", "This study investigated the relative effects of distributed constraint-induced therapy (CIT) and bilateral arm training (BAT) on motor performance, daily function, functional use of the affected arm, and quality of life in patients with hemiparetic stroke.\n A total of 60 patients were randomized to distributed CIT, BAT, or a control intervention of less specific but active therapy. Each group received intensive training for 2 hours/day, 5 days/week, for 3 weeks. Pretreatment and posttreatment measures included the Fugl-Meyer Assessment (FMA), Functional Independence Measure (FIM), Motor Activity Log (MAL), and Stroke Impact Scale (SIS). The proximal and distal scores of FMA were used to examine separate upper limb (UL) elements of movement.\n The distributed CIT and BAT groups showed better performance in the overall and the distal part score of the FMA than the control group. The BAT group exhibited greater gains in the proximal part score of the FMA than the distributed CIT and control groups. Enhanced performance was found for the distributed CIT group in the MAL, the subtest of locomotion in the FIM, and certain domains of the SIS (eg, ADL/IADL).\n BAT may uniquely improve proximal UL motor impairment. In contrast, distributed CIT may produce greater functional gains for the affected UL in subjects with mild to moderate chronic hemiparesis." ]

[ "16507032", "15966958", "18843564", "19664653", "15113492", "20008945", "15318916", "15966959", "9366661" ]

[ "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.", "Physical health--a cluster randomized controlled lifestyle intervention among persons with a psychiatric disability and their staff.", "Five years of lifestyle intervention improved self-reported mental and physical health in a general population: the Inter99 study.", "Exploratory cluster randomised controlled trial of shared care development for long-term mental illness.", "A randomized trial of medical care management for community mental health settings: the Primary Care Access, Referral, and Evaluation (PCARE) study.", "Developing methods for systematic reviewing in health services delivery and organization: an example from a review of access to health care for people with learning disabilities. Part 1. Identifying the literature.", "An exploratory study of assertive community treatment for people with intellectual disability and psychiatric disorders: conceptual, clinical, and service issues.", "A randomized trial of assertive community treatment for homeless persons with severe mental illness." ]

[ "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 objective was to explore the impact on physical health of a lifestyle programme among persons with psychiatric disabilities, and their caregivers. Their satisfaction with the intervention was also assessed. Somatic comorbidity and an increased mortality related to the lifestyle among persons with psychiatric disabilities are well known. Few randomized controlled trials have been aimed specifically at lifestyle issues among persons with a psychiatric disability. This trial includes clients with psychiatric disabilities living in supported housing and their staff. Forty-one persons with a DSM-?V diagnosis of severe mental illness from psychiatric disability from 10 supported housing facilities and 41 of their caregivers participated in this 12-month study during 2005-2006 in Sweden. The supported housing facilities with residents and staff were randomly assigned to either a health intervention programme or a control programme with an aesthetic content. The presence of metabolic syndrome and changes in the mean of physiological parameters such as Hba1c, P-glucose, P-insulin, lipids, blood pressure, physical working capacity, body mass index, Heart Score were investigated and participants' satisfaction assessed. There was a significant reduction in the mean of metabolic syndrome criteria in the intervention group compared with the control group at the follow-up. The participants expressed satisfaction with the programme. The results indicate that health interventions on lifestyle issues when involving carers are appreciated, feasible and could be successful in reducing some health-related risk factors among persons with psychiatric disabilities.", "Self-reported health has been shown to predict mortality. We lack knowledge on whether a lifestyle intervention can improve self-reported mental and physical health in a general population.\n Inter99, Denmark (1999-2006) is a randomised population-based intervention study. We screened for ischemic heart disease and repeatedly offered advice and assistance to obtain a healthier lifestyle. Health related quality of life was measured by Short Form 12 (SF-12); completed by 9322 at baseline and 7719 at five-year follow-up. In linear mixed models we investigated the effect of the intervention on self-reported health over time.\n At baseline men had higher physical health-component scores (PCS) than women. Living with a partner, being employed, and being healthy was associated with high PCS. The mental health-component scores (MCS) showed the same socio-demographic differences, except that MCS increased with age. Significantly fewer participants in the intervention groups had decreased their PCS and MCS compared with the control group. Adjusted multilevel analyses confirmed that the intervention significantly improved physical- (p=0.008) and mental health (p<0.001) over time compared with the control group.\n Screening for ischemic heart disease and offering lifestyle intervention had a significantly beneficial effect on mental and physical self-reported health in the long term in a general population.", "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.", "Poor quality of healthcare contributes to impaired health and excess mortality in individuals with severe mental disorders. The authors tested a population-based medical care management intervention designed to improve primary medical care in community mental health settings.\n A total of 407 subjects with severe mental illness at an urban community mental health center were randomly assigned to either the medical care management intervention or usual care. For individuals in the intervention group, care managers provided communication and advocacy with medical providers, health education, and support in overcoming system-level fragmentation and barriers to primary medical care.\n At a 12-month follow-up evaluation, the intervention group received an average of 58.7% of recommended preventive services compared with a rate of 21.8% in the usual care group. They also received a significantly higher proportion of evidence-based services for cardiometabolic conditions (34.9% versus 27.7%) and were more likely to have a primary care provider (71.2% versus 51.9%). The intervention group showed significant improvement on the SF-36 mental component summary (8.0% [versus a 1.1% decline in the usual care group]) and a nonsignificant improvement on the SF-36 physical component summary. Among subjects with available laboratory data, scores on the Framingham Cardiovascular Risk Index were significantly better in the intervention group (6.9%) than the usual care group (9.8%).\n Medical care management was associated with significant improvements in the quality and outcomes of primary care. These findings suggest that care management is a promising approach for improving medical care for patients treated in community mental health settings.", "Our objectives were to identify literature on: (i) theory, evidence and gaps in knowledge relating to the help-seeking behaviour of people with learning disabilities and their carers; (ii) barriers experienced by people with learning disabilities in securing access to the full range of health services; (iii) interventions which improve access to health services by people with learning disabilities.\n twenty-eight bibliographic databases, research registers, organizational websites or library catalogues; reference lists from identified studies; contact with experts; current awareness and contents alerting services in the area of learning disabilities.\n Inclusion criteria were English language literature from 1980 onwards, relating to people with learning disabilities of any age and all study designs. The main criteria for assessment was relevance to the Guilliford et al. model of access to health care (Gulliford et al. Access to health care. Report of a Scoping Exercise for the National Co-ordinating Centre for NHS Service Delivery and Organisation R & D (NCCSDO). London: NCCSDO, 2001), which was modified to the special needs of people with learning disabilities. Inclusion criteria focused on relevance to the model with initial criteria revised in light of literature identified and comments from a consultation exercise with people with learning disabilities, family and paid carers and experts in the field. Data abstraction was completed independently and selected studies were evaluated for scientific rigour and the results synthesized.\n In total, 2221 items were identified as potentially relevant and 82 studies fully evaluated.\n The process of identifying relevant literature was characterized by a process of clarifying the concept under investigation and sensitive search techniques which led to an initial over-identification of non-relevant records from database searches. Thesaurus terms were of limited value, forcing a reliance on using free-text terms and alternative methods of identifying literature to supplement and improve the recall of the database searches. A key enabler in identifying relevant literature was the depth and breadth of knowledge built up by the reviewers whilst engaged in this process.", "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.", "This experiment evaluated the effectiveness of an innovative program of assertive community treatment (ACT) for homeless persons with severe and persistent mental illnesses.\n One hundred fifty-two homeless persons with severe and persistent mental illness were randomized to either the experimental ACT program or to usual community services. Baseline assessments included the Structured Clinical Interview for DSM-III-R, Quality-of-Life Interview, Colorado Symptom Index, and the Medical Outcomes Study 36-Item Short Form Health Survey. All assessments (except the Structured Clinical Interview) were repeated at the 2-, 6-, and 12-month follow-up evaluations.\n Subjects in the ACT program used significantly fewer psychiatric inpatient days, fewer emergency department visits, and more psychiatric outpatient visits than the comparison subjects. The ACT subjects also spent significantly more days in stable community housing, and they experienced significantly greater improvements in symptoms, life satisfaction, and perceived health status.\n Relative to usual community care, the ACT program for homeless persons with severe and persistent mental illness shifts the locus of care from crisis-oriented services to ongoing outpatient care and produces better housing, clinical, and life satisfaction outcomes." ]

[ "20346030", "1439601", "10646679", "19815264", "15879805", "2039294", "16527562", "10569535", "12508134" ]

[ "Extracorporeal shockwave lithotripsy vs ureteroscopy as first-line therapy for patients with single, distal ureteric stones: a prospective randomized study.", "Cost effectiveness of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy for medium-sized kidney stones. A randomised clinical trial.", "Treatment for extended-mid and distal ureteral stones: SWL or ureteroscopy? Results of a multicenter study.", "A prospective randomized study comparing shock wave lithotripsy and semirigid ureteroscopy for the management of proximal ureteral calculi.", "Prospective, randomized trial comparing shock wave lithotripsy and ureteroscopy for lower pole caliceal calculi 1 cm or less.", "Choledocholithiasis. Endoscopic sphincterotomy or common bile duct exploration.", "Prospective randomized trial comparing shock wave lithotripsy and ureteroscopic lithotripsy for management of large upper third ureteral stones.", "Extracorporeal shock wave lithotripsy versus ureteroscopy for distal ureteral calculi: a prospective randomized study.", "Extracorporeal shock-wave versus pneumatic ureteroscopic lithotripsy in treatment of lower ureteral calculi." ]

[ "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 evaluate percutaneous nephrolithotomy (PNL) and extracorporeal shock wave lithotripsy (ESWL) for their clinical effects, their cost effectiveness, their complication rates, and the patients' experiences, 55 consecutive patients were randomised to have one or other operation between October 1986 and October 1988. Six patients were excluded, 21 were treated with PNL and 28 with ESWL as primary treatment. Mean hospital stay and length of treatment were longer for PNL than for ESWL. Since 1 July 1987 all patients having ESWL have been treated without anaesthesia (n = 15), whereas epidural anaesthesia was used for all PNL. Slightly more of the ESWL patients experienced some pain during treatment. Minor complications or pain were more common after ESWL during the first 10 days after discharge from hospital. If patients with stone fragments of 4 mm or less were regarded as having a successful outcome, the success rates after one year were 94% for PNL and 77% for ESWL. The overall total cost was lower for ESWL than for PNL, the cost per successfully treated patient being 2172 pounds for PNL and 1810 pounds for ESWL. Medium sized kidney stones (6-30 mm, or 2-3 stones of 20 mm or less) can be efficiently and cheaply treated by both PNL and ESWL, though the cost of ESWL is lower. Even if effects other than cost (such as complications and patients' experience) are borne in mind, ESWL was superior to PNL for this group of patients.", "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 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).", "The optimal management of lower pole renal calculi is controversial. We compared shock wave lithotripsy (SWL) and ureteroscopy (URS) for the treatment of patients with small lower pole stones in a prospective, randomized, multicenter trial.\n A total of 78 patients with 1 cm or less isolated lower pole stones were randomized to SWL or URS. The primary outcome measure was stone-free rate on noncontrast computerized tomography at 3 months. Secondary outcome parameters were length of stay, complication rates, need for secondary procedures and patient derived quality of life measures.\n A total of 67 patients randomized to SWL (32) or URS (35) completed treatment. The 2 groups were comparable with respect to age, sex, body mass index, side treated and stone surface area. Operative time was significantly shorter for SWL than URS (66 vs 90 minutes). At 3 months of followup 26 and 32 patients who underwent SWL and URS had radiographic followup that demonstrated a stone-free rate of 35% and 50%, respectively (p not significant). Intraoperative complications occurred in 1 SWL case (unable to target stone) and in 7 URS cases (failed access in 5 and perforation in 2), while postoperative complications occurred in 7 SWL and 7 URS cases. Patient derived quality of life measures favored SWL.\n This study failed to demonstrate a statistically significant difference in stone-free rates between SWL and URS for the treatment of small lower pole renal calculi. However, SWL was associated with greater patient acceptance and shorter convalescence.", "A prospective randomized trial was conducted of preoperative endoscopic sphincterotomy and surgery (ES&S) or surgery alone (SA) in 52 patients with cholecystolithiasis and choledocholithiasis that were candidates for elective surgery. After ES&S 65% of patients were stone free. Eighty-eight per cent of patients with SA were stone free after surgery (p less than 0.05). Three patients in each group had residual stones at the completion of the operation. Five of these six had more than 20 common bile duct (CBD) stones. There was one episode of major hemorrhage in a patient in each group and no deaths. Costs were essentially equal for the individual patient with a successful ES as compared to SA. Societal costs of a program of preoperative endoscopic retrograde cholangiopancreatography and ES would be higher because of the cost of screening for patients with CBD stones. These results do not support preoperative ES as a technique for clearance of the CBD of stones on the basis of efficacy, morbidity rate, or cost.", "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.", "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 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." ]

[ "15457381", "16481296", "12235507", "11729380", "1534528", "14760660", "14598412", "7489170", "16365239" ]

[ "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.", "Laparoscopic cholecystectomy versus mini-laparotomy cholecystectomy: a prospective, randomized, single-blind study.", "[Laparoscopic cholecystectomy versus mini-lap-cholecystectomy. Results of a prospective, randomized study].", "Randomized clinical trial of virtual reality simulation for laparoscopic skills training.", "Randomized clinical trial of laparoscopic cholecystectomy performed with mini-instruments.", "Randomized trial of laparoscopic cholecystectomy and mini-cholecystectomy.", "Advantages of mini-laparoscopic vs conventional laparoscopic cholecystectomy: results of a prospective randomized trial." ]

[ "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.", "To analyze outcomes after open small-incision surgery (minilaparotomy) and laparoscopic surgery for gallstone disease in general surgical practice.\n This study was a randomized, single-blind, multicenter trial comparing laparoscopic cholecystectomy (LC) to minilaparotomy cholecystectomy (MC). Both elective and acute patients were eligible for inclusion. All surgeons normally performing cholecystectomy, both trainees under supervision and consultants, operated on randomized patients. LC was a routine procedure at participating hospitals, whereas MC was introduced after a short training period. All nonrandomized cholecystectomies at participating units during the study period were also recorded to analyze the external validity of trial results. The randomization period was from March 1, 1997, to April 30, 1999.\n Of 1,705 cholecystectomies performed at participating units during the randomization period, 724 entered the trial and 362 patients were randomized to each of the procedures. The groups were well matched for age and sex, but there were fewer acute operations in the LC group than the MC group. In the LC group 264 and in the MC group 150 operations were performed by surgeons who had done more than 25 operations of that type. Median operating times were 100 and 85 minutes for LC and MC, respectively. Median hospital stay was 2 days in each group, but in a nonparametric test it was significantly shorter after LC. Median sick leave and time for return to normal recreational activities were shorter after LC than MC. Intraoperative complications were less frequent in the MC group, but there was no difference in the postoperative complication rate between the groups. There was one serious bile duct injury in each group, but no deaths.\n Operating time was longer and convalescence was smoother for LC compared with MC. Further analyses of LC versus MC are necessary regarding surgical training, surgical outcome, and health economy.", "Laparoscopic cholecystectomy (LCCE) was gaining acceptance rapidly, when several institutions could demonstrate the safety of this minimal invasive treatment modality. Nevertheless prospective randomised studies still are missing to prove the advantages of this new treatment modality in contrast to open cholecystectomy. 77 patients with symptomatic cholelithiasis were treated by LCCE (n = 40) or mini-lap CCE (n = 37) in a prospective, randomised study. As preliminary results, there were no differences in duration of anesthesia and operation time, perioperative complications or postoperative need for analgetics. Patients with LCCE had significant less postoperative pain, less restriction of total vital capacity and a shorter postoperative hospital stay as parameters of a diminished operative trauma.", "This study examined the impact of virtual reality (VR) surgical simulation on improvement of psychomotor skills relevant to the performance of laparoscopic cholecystectomy.\n Sixteen surgical trainees performed a laparoscopic cholecystectomy on patients in the operating room (OR). The participants were then randomized to receive VR training (ten repetitions of all six tasks on the Minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR)) or no training. Subsequently, all subjects performed a further laparoscopic cholecystectomy in the OR. Both operative procedures were recorded on videotape, and assessed by two independent and blinded observers using predefined objective criteria. Time to complete the procedure, error score and economy of movement score were assessed during the laparoscopic procedure in the OR.\n No differences in baseline variables were found between the two groups. Surgeons who received VR training performed laparoscopic cholecystectomy significantly faster than the control group (P=0.021). Furthermore, those who had VR training showed significantly greater improvement in error (P=0.003) and economy of movement (P=0.003) scores.\n Surgeons who received VR simulator training showed significantly greater improvement in performance in the OR than those in the control group. VR surgical simulation is therefore a valid tool for training of laparoscopic psychomotor skills and could be incorporated into surgical training programmes.\n Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "The outcomes after traditional laparoscopic cholecystectomy (LC; one 10-mm port, one 12-mm port and two 5-mm ports) and minilaparoscopic cholecystectomy (MLC; three 3-mm ports and one 12-mm port) for gallstone disease were compared.\n The study was a randomized, single-blind trial comparing LC with MLC. Only elective patients were eligible for inclusion. LC was a routine procedure at the institution in which the study was performed, whereas MLC was introduced after a short training period. The randomization period was from January to December 2001.\n Of 175 patients who had elective minimal access cholecystectomy during the randomization period, 135 entered the trial: 68 underwent LC and 67 underwent MLC. The groups were matched for age, sex and preoperative characteristics. Median (range) operating times for LC and MLC were similar (45 (20-120) and 50 (20-170) min respectively). Intraoperative and postoperative complication rates, the time for the patient to resume walking, eating and passing stools, and median hospital stay were the same in the two groups. The level of postoperative pain was lower in the MLC group at 1 h (P = 0.011), 3 h (P = 0.012), 6 h (P = 0.003), 12 h (P = 0.052) and 24 h (P = 0.034). Patients who had MLC received fewer injections of analgesic (P = 0.036) and more patients in this group expressed satisfaction with the cosmetic result (P = 0.001).\n MLC took a similar time to perform and caused less postoperative pain than the standard laparoscopic procedure. Reducing the port size further enhanced the advantages of laparoscopic over open cholecystectomy.\n Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "Three hundred and ten patients having elective cholecystectomy were randomized to either laparoscopic cholecystectomy or mini-cholecystectomy. There were 155 patients in each group. Conversion to open cholecystectomy was significantly more common with laparoscopic cholecystectomy (13 versus 4 per cent) and complications were significantly more frequent with laparoscopic cholecystectomy (9 versus 3 per cent). If laparoscopic cholecystectomy was successful, hospital stay was significantly shorter than for mini-cholecystectomy (2 versus 3 days respectively), but overall the hospital stay was not significantly different. Postoperative analgesia requirements were reduced and return to normal activities and to work were faster after laparoscopic cholecystectomy. There was no significant cost difference between the two procedures.", "The use of smaller instruments during laparoscopic cholecystectomy (LC) has been proposed to reduce postoperative pain and improve cosmesis. However, despite several recent trials, the effects of the use of miniaturized instruments for LC are not well established. We hypothesized that LC using miniports (M-LC) is safe and produces less incisional pain and better cosmetic results than LC performed conventionally (C-LC).\n A patient- and observer-blinded, randomized, prospective clinical trial.\n A tertiary care, university-based hospital.\n Seventy-nine patients scheduled for an elective LC who agreed to participate in this trial were randomized to undergo surgery using 1 of the 2 instrument sets. The criteria for exclusion were American Society of Anesthesiologists class III or IV, age older than 70 years, liver or coagulation disorders, previous major abdominal surgical procedures, and acute cholecystitis or acute choledocholithiasis.\n Laparoscopic cholecystectomy performed with either conventional or miniaturized instruments.\n Patients' age, sex, operative time, operative blood loss, intraoperative complications, early and late postoperative incisional pain, and cosmetic results.\n Thirty-three C-LCs and 34 M-LCs were performed and analyzed. There were 8 conversions (24%) to the standard technique in the M-LC group. No intraoperative or major postoperative complications occurred in either group. The average incisional pain score on the first postoperative day was significantly less in the M-LC group (3.9 vs 4.9; P = .04). No significant differences occurred in the mean scores for pain on postoperative days 3, 7, and 28. However, 90% of patients in the M-LC group and only 74% of patients in the C-LC group had no pain (visual analog scale score of 0) at 28 days postoperatively (P = .05). Cosmetic results were superior in the M-LC group according to both the study nurse's and the patients' assessments (38.9 vs 28.9; P<.001, and 38.8 vs 33.4; P = .001, respectively).\n Laparoscopic cholecystectomy can be safely performed using 10-mm umbilical, 5-mm epigastric, 2-mm subcostal, and 2-mm lateral ports. The use of mini-laparoscopic techniques resulted in decreased early postoperative incisional pain, avoided late incisional discomfort, and produced superior cosmetic results. Although improved instrument durability and better optics are needed for widespread use of miniport techniques, this approach can be routinely offered to many properly selected patients undergoing elective LC." ]

[ "20566605", "11242425", "16212203", "15293973", "12727395", "17398310", "7914260", "16183590", "3566318" ]

[ "Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy.", "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.", "The first six month growth and illness of exclusively and non-exclusively breast-fed infants in Nigeria.", "Effect of community-based promotion of exclusive breastfeeding on diarrhoeal illness and growth: a cluster randomised controlled trial.", "Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study.", "Effects of age of introduction of complementary foods on infant breast milk intake, total energy intake, and growth: a randomised intervention study in Honduras.", "Breast-feeding, return of menses, sexual activity and contraceptive practices among mothers in the first six months of lactation in Onitsha, South Eastern Nigeria.", "Prolonged exclusive breast feeding and heredity as determinants in infantile atopy." ]

[ "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.", "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.", "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.", "Exclusive breastfeeding is recommended until age 6 months. We assessed the feasibility, effectiveness, and safety of an educational intervention to promote exclusive breastfeeding for this length of time in India.\n We developed the intervention through formative research, pair-matched eight communities on their baseline characteristics, and randomised one of each pair to receive the intervention and the other to no specific intervention. We trained health and nutrition workers in the intervention communities to counsel mothers for exclusive breastfeeding at multiple opportunities. We enrolled 1115 infants born in the 9 months after training-552 in the intervention and 473 in the control communities. Feeding at age 3 months, and anthropometry and of diarrhoea prevalence at age 3 months and 6 months were assessed. All analyses were by intention to treat.\n We assessed 483 and 412 individuals at 3 months in the intervention and control groups, respectively, and 468 and 412 at 6 months. At 3 months, exclusive breastfeeding rates were 79% (381) in the intervention and 48% (197) in the control communities (odds ratio 4.02, 95% CI 3.01-5.38, p<0.0001). The 7-day diarrhoea prevalence was lower in the intervention than in the control communities at 3 months (0.64, 0.44-0.95, p=0.028) and 6 months (0.85, 0.72-0.99, p=0.04). The mean weights and lengths, and the proportion with weight-for-height or height-for-age Z scores of 2 or less, at age 3 months and 6 months did not differ much between groups. Intervention effect on exclusive breastfeeding, diarrhoeal morbidity, and anthropometry at age 6 months in the low-birthweight subgroup was similar to that for all births.\n Promotion of exclusive breastfeeding until age 6 months in a developing country through existing primary health-care services is feasible, reduces the risk of diarrhoea, and does not lead to growth faltering.", "Exclusive breastfeeding, though better than other forms of infant feeding and associated with improved child survival, is uncommon. We assessed the HIV-1 transmission risks and survival associated with exclusive breastfeeding and other types of infant feeding.\n 2722 HIV-infected and uninfected pregnant women attending antenatal clinics in KwaZulu Natal, South Africa (seven rural, one semiurban, and one urban), were enrolled into a non-randomised intervention cohort study. Infant feeding data were obtained every week from mothers, and blood samples from infants were taken monthly at clinics to establish HIV infection status. Kaplan-Meier analyses conditional on exclusive breastfeeding were used to estimate transmission risks at 6 weeks and 22 weeks of age, and Cox's proportional hazard was used to quantify associations with maternal and infant factors.\n 1132 of 1372 (83%) infants born to HIV-infected mothers initiated exclusive breastfeeding from birth. Of 1276 infants with complete feeding data, median duration of cumulative exclusive breastfeeding was 159 days (first quartile [Q1] to third quartile [Q3], 122-174 days). 14.1% (95% CI 12.0-16.4) of exclusively breastfed infants were infected with HIV-1 by age 6 weeks and 19.5% (17.0-22.4) by 6 months; risk was significantly associated with maternal CD4-cell counts below 200 cells per muL (adjusted hazard ratio [HR] 3.79; 2.35-6.12) and birthweight less than 2500 g (1.81, 1.07-3.06). Kaplan-Meier estimated risk of acquisition of infection at 6 months of age was 4.04% (2.29-5.76). Breastfed infants who also received solids were significantly more likely to acquire infection than were exclusively breastfed children (HR 10.87, 1.51-78.00, p=0.018), as were infants who at 12 weeks received both breastmilk and formula milk (1.82, 0.98-3.36, p=0.057). Cumulative 3-month mortality in exclusively breastfed infants was 6.1% (4.74-7.92) versus 15.1% (7.63-28.73) in infants given replacement feeds (HR 2.06, 1.00-4.27, p=0.051).\n The association between mixed breastfeeding and increased HIV transmission risk, together with evidence that exclusive breastfeeding can be successfully supported in HIV-infected women, warrant revision of the present UNICEF, WHO, and UNAIDS infant feeding guidelines.", "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.", "The objective of this study was to determine the exclusive breast-feeding practices, return of menstruation, sexual activity and contraceptive practices among breast-feeding mothers in the first six months of lactation. The study was based in Onitsha, South Eastern Nigeria. A structured questionnaire was used to obtain data from breast-feeding mothers on their age, educational attainment, breast-feeding practices, return of menstruation, sexual activity and contraceptive practices within the first six months of lactation at intervals of 6 weeks, 10 weeks 14 weeks and 6 months post delivery. Analysis of the information obtained showed that out of the 178 mothers who participated in the study 81% of the mothers were within the ages of 20 - 34 years. While all the mothers had formal education, the majority (59%) had secondary education. Seventy-three percent initiated breast-feeding within one hour of delivery. On discharge from hospital, all of them had already established breast-feeding which continued up to six weeks and dropped to 97.8% at six months. Exclusive breast-feeding which was practised by 100% on discharge dropped to 3.9% at six months. The feeding regimen was on demand as practised by 98.9% of the mothers. Menstrual flow had returned in 33.8% of the mothers by 6 weeks of lactation, and had risen to 70.2% at six months. There was more prolonged lactational amenorrheoa in exclusively breast-feeding mothers than in those who were not. By 6 weeks post delivery 31.6% of the mothers had resumed sexual activity and this rose to 93.6% at six months. With the resumption of sexual activity only 5% of the mothers resorted to contraceptive practices other than lactational amenorrhea and this increased to 54% at six months. There was no pregnancy in any of these women during the six months period. While appreciating the role of lactational amenorrhea in child spacing and considering the early return of sexual activity among the mothers the practice of introducing contraceptive practices needs to be encouraged especially in women whose menstruation has returned.", "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." ]

[ "3338348", "10232210", "8576671", "3364765", "3324616", "3200596", "7082061", "2926558", "2407164" ]

[ "Patient-controlled analgesia vs. conventional intramuscular analgesia following colon surgery.", "Preoperative PCA teaching program to manage postoperative pain.", "Cost-effectiveness analysis of patient-controlled analgesia, intramuscular q.i.d. injection and p.r.n. injection for postoperative pain relief.", "A statistical model for pain in patient-controlled analgesia and conventional intramuscular opioid regimens.", "Patient-controlled analgesia: a controlled trial.", "Patient-controlled analgesia: a randomized, prospective comparison between two commercially available PCA pumps and conventional analgesic therapy for postoperative pain.", "Patient-controlled analgesia: a new concept of postoperative pain relief.", "A study of pain management: patient controlled analgesia versus intramuscular analgesia.", "A prospective study of patient-controlled analgesia. Impact on overall hospital course." ]

[ "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.", "Patient-controlled analgesia (PCA) therapy was designed to provide patients with greater control in managing their pain. However, many patients continue to suffer from moderate to severe pain due to lack of knowledge about how to use PCA therapy. The results of this quasi-experimental study demonstrated that patients who received structured preoperative teaching had statistically significant higher knowledge regarding the use of PCA therapy and more positive attitudes toward using pain medicine. Patients who received the video teaching reported better pain control and satisfaction with pain management 4 and 8 hours following their surgical procedures.", "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.", "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.", "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.", "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 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.", "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.", "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." ]

[ "12876092", "12392866", "2304219", "769027", "15082724", "19724045", "7428142", "20679560", "16904951" ]

[ "Factors associated with failure to publish large randomized trials presented at an oncology meeting.", "The end-of-study patient survey: methods influencing response rate in the AVID Trial.", "A cohort study of summary reports of controlled trials.", "An example of European multicenter trials: multispectral analysis of clozapine.", "Factors associated with breast cancer clinical trials participation and enrollment at a large academic medical center.", "Comparison of registered and published primary outcomes in randomized controlled trials.", "Recruitment of patients to cooperative group clinical trials.", "Outcome reporting among drug trials registered in ClinicalTrials.gov.", "A randomised trial of the effects of an additional communication strategy on recruitment into a large-scale, multi-centre trial." ]

[ "Large clinical trials are the criterion standard for making treatment decisions, and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions.\n To determine the rate of full publication of large randomized trials presented at annual meetings of the American Society of Clinical Oncology (ASCO), quantify bias against publishing nonsignificant results, and identify factors associated with time to publication.\n Survey of 510 abstracts from large (sample size, > or =200), phase 3, randomized controlled trials presented at ASCO meetings between 1989 and 1998. Trial results were classified as significant (P< or =.05 for the primary outcome measure) or nonsignificant (P>.05 or not reported), and the type of presentation and sponsorship were identified. Subsequent full publication was identified using a search of MEDLINE and EMBASE, completed November 1, 2001; the search was updated in November 2002, using the Cochrane Register of Controlled Trials. Authors were contacted if the searches did not find evidence of publication.\n Publication rate at 5 years; time from presentation to full publication.\n Of 510 randomized trials, 26% were not published in full within 5 years after presentation at the meeting. Eighty-one percent of the studies with significant results had been published by this time compared with 68% of the studies with nonsignificant results (P<.001). Studies with oral or plenary presentation were published sooner than those not presented (P =.002), and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified (P =.02). These factors remained significant in a multivariable model. The most frequent reason cited by authors for not publishing was lack of time, funds, or other resources.\n A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation. Bias against publishing nonsignificant results is a problem even for large randomized trials. Nonpublication breaks the contract that investigators make with trial participants, funding agencies, and ethics boards.", "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.", "Substantial numbers of clinical trials continue to be reported only in summary reports that present insufficient methodological details to permit informed judgments about the likely validity of the conclusions. Using a cohort of 176 controlled trials reported in summary form, we tested the hypotheses that they would be more likely to be followed by full reports if, on the basis of the information provided in the summary report, (1) the trial was judged to be methodologically sound, (2) the results favored the test treatment, and (3) the sample size was relatively large. The results of univariate and multivariate analyses provided support for only the third of these hypotheses. Investigators, as well as those who fund and sanction the conduct of clinical research, should make greater efforts to ensure that clinical trials are reported properly.", "nan", "The practice patterns of medical oncologists at a large National Cancer Institute Comprehensive Cancer Center in Detroit, MI were evaluated to better understand factors associated with accrual to breast cancer clinical trials.\n From 1996 to 1997, physicians completed surveys on 319 of 344 newly evaluated female breast cancer patients. The 19-item survey included clinical data, whether patients were offered clinical trial (CT) participation and enrollment, and when applicable, reasons why they were not. Multivariate analyses using logistic regression were performed to evaluate predictors of an offer and enrollment.\n The patients were 57% white, 32% black, and 11% other/unknown race. One hundred six (33%) were offered participation and 36 (34%) were enrolled. In multivariate analysis, CTs were less likely offered to older women (mean age, 52 years for those offered v 57 years for those not offered; P =.0005) and black women (21% of blacks offered v 42% of whites; P =.0009). Women with stage 1 disease, poor performance status, and those who were previously diagnosed were also less likely to be offered trials. None of these factors were significant predictors of enrollment. Women were not offered trials because of ineligibility (57%), lack of available trials (41%), and noncompliance (2%). Reasons for failed enrollment included patient refusal (88%) and failed eligibility (12%).\n It is important for cooperative groups to design studies that will accommodate a broader spectrum of patients. Further work is needed to assess ways to improve communication about breast cancer CT participation to all eligible women.", "As of 2005, the International Committee of Medical Journal Editors required investigators to register their trials prior to participant enrollment as a precondition for publishing the trial's findings in member journals.\n To assess the proportion of registered trials with results recently published in journals with high impact factors; to compare the primary outcomes specified in trial registries with those reported in the published articles; and to determine whether primary outcome reporting bias favored significant outcomes.\n MEDLINE via PubMed was searched for reports of randomized controlled trials (RCTs) in 3 medical areas (cardiology, rheumatology, and gastroenterology) indexed in 2008 in the 10 general medical journals and specialty journals with the highest impact factors.\n For each included article, we obtained the trial registration information using a standardized data extraction form.\n Of the 323 included trials, 147 (45.5%) were adequately registered (ie, registered before the end of the trial, with the primary outcome clearly specified). Trial registration was lacking for 89 published reports (27.6%), 45 trials (13.9%) were registered after the completion of the study, 39 (12%) were registered with no or an unclear description of the primary outcome, and 3 (0.9%) were registered after the completion of the study and had an unclear description of the primary outcome. Among articles with trials adequately registered, 31% (46 of 147) showed some evidence of discrepancies between the outcomes registered and the outcomes published. The influence of these discrepancies could be assessed in only half of them and in these statistically significant results were favored in 82.6% (19 of 23).\n Comparison of the primary outcomes of RCTs registered with their subsequent publication indicated that selective outcome reporting is prevalent.", "One of the prerequisites for a successful clinical trial is the accrual of a sufficient number of patients for study. Because the sample-size requirements for a randomized clinical trial can rarely be met by a single institution in a short period of time, cooperative groups have taken in a major role in conducting clinical trials. In this paper, the recruitment of patients at our institution to a lung cancer clinical trial is evaluated. A total of 653 lung cancer cases were reviewed. Of the 77 cases which were eligible for the trial, 41 were accessioned. The reasons why eligible patients were not accessioned to the trial are discussed.", "Clinical trial registries are in widespread use to promote transparency around trials and their results.\n To describe characteristics of drug trials listed in ClinicalTrials.gov and examine whether the funding source of these trials is associated with favorable published outcomes.\n An observational study of safety and efficacy trials for anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators conducted between 2000 and 2006.\n ClinicalTrials.gov, a Web-based registry of clinical trials launched in 1999.\n Publications resulting from the trials for the 5 drug categories of interest were identified, and data were abstracted on the trial record and publication, including timing of registration, elements of the study design, funding source, publication date, and study outcomes. Assessments were based on the primary funding categories of industry, government agencies, and nonprofit or nonfederal organizations.\n Among 546 drug trials, 346 (63%) were primarily funded by industry, 74 (14%) by government sources, and 126 (23%) by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or nonfederal organization-funded trials (P < 0.001). Trials funded by nonprofit or nonfederal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs. 61.2%; P = 0.013). Rates of trial publication within 24 months of study completion ranged from 32.4% among industry-funded trials to 56.2% among nonprofit or nonfederal organization-funded trials without industry contributions (P = 0.005 across groups).\n The publication status of a trial could not always be confirmed, which could result in misclassification. Additional information on study protocols and comprehensive trial results were not available to further explore underlying factors for the association between funding source and outcome reporting.\n In this sample of registered drug trials, those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources.\n National Library of Medicine and National Institute of Child Health and Human Development, National Institutes of Health.", "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." ]

[ "9084544", "8198263", "9380919", "1606094", "1539776", "3565725", "10213716", "10392674", "2334627" ]

[ "Prophylaxis against acid aspiration in regional anesthesia for elective cesarean section: a comparison between oral single-dose ranitidine, famotidine and omeprazole assessed with fiberoptic gastric aspiration.", "Intravenous administration of the proton pump inhibitor omeprazole reduces the risk of acid aspiration at emergency cesarean section.", "[Prophylaxis of intraoperative nausea and vomiting with sub-hypnotic dose of propofol during intradural anesthesia in cesarean section].", "The antiemetic efficacy and safety of prophylactic metoclopramide for elective cesarean delivery during spinal anesthesia.", "A comparison of omeprazole and ranitidine for prophylaxis against aspiration pneumonitis in emergency caesarean section.", "The effect of different pre-operative feeding regimens on plasma glucose and gastric volume and pH in infancy.", "Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery.", "Thoracic epidural anesthesia as an adjunct to general anesthesia for cardiac surgery: effects on ventilation-perfusion relationships.", "Aspiration pneumonitis prophylaxis in obstetric anaesthesia: comparison of effervescent cimetidine-sodium citrate mixture and sodium citrate." ]

[ "Acid aspiration syndrome is still an important cause which contributes to maternal mortality in obstetric anesthesia. In this study, we compared famotidine, ranitidine, omeprazole with placebo for prophylaxis against aspiration pneumonitis in elective Cesarean section under regional anesthesia.\n One hundred and sixty patients undergoing elective Cesarean section under spinal anesthesia were allocated randomly into four groups: Group P (n = 40) received placebo only; Group F (n = 40) received famotidine 40 mg Group R (n = 40) received ranitidine 300 mg; and Group O (n = 40) received omeprazole 40 mg. All drugs were given orally at least three hours before the patients entering the operating room. Gastric content was directly aspirated and measured respectively with a flexible fiberoscope under visualization and by a pH meter after delivery.\n Although these three drugs (F, R, and O) were all effective in controlling the secretion of gastric acid, from gastric analysis it was demonstrated that famotidine and ranitidine could be more defective to neutralize acidity than omeprazole (p < 0.05). Percentages of patients with pH < or = 2.5 in Groups P, F, R, and O were respectively 88%, 10%, 8%, and 21%, showing that the innate pH of gastric juice was far lower than expected. Patients receiving omeprazole in single oral dose regimen retained a greater gastric volume (> or = 0.4 ml/kg) than those who received famotidine or ranitidine (p < 0.005). From the criteria defining the patients \"at risk\" (pH < or = 2.5 and gastric volume > or = 0.4 ml/kg), it is speculated that all these three regimens could potentially reduce the incidence of patients with calculated risk.\n Our data demonstrated that parturients under regional anesthesia were at a higher risk of aspiration pneumonitis than generally thought. Single dose of ranitidine or famotidine administered orally three hours before surgery provided a more effective means to control and neutralize gastric secretion than omeprazole in parturients.", "This study documented gastric pH and volume, and the number of patients at risk for acid aspiration of gastric contents, in a group of mothers undergoing emergency cesarean section under general anesthesia. Patients were randomized in a double-blind fashion to receive omeprazole 40 mg intravenously or placebo at the time of decision to proceed to cesarean section. In addition, all patients received 10 mg intravenous metoclopramide and 30 mL of 0.3 M sodium citrate. Aspiration of gastric contents was undertaken immediately after endotracheal intubation (PI) and before tracheal extubation (PE). Patients with both pH < 3.5 and volume > 25 mL were deemed to be at risk of acid aspiration should regurgitation occur. Only cases where the study-drug-to-PI-aspiration interval was > 30 min were evaluated. There were 282 patients in the study group and 259 in the control group. PI, 11 patients (4.25%; 95% confidence interval [CI] 1.79-6.71) were at risk in the control group compared with 4 (1.42%; 95% CI 0.04-2.8) in the study group (P = 0.045). The omeprazole-to-PI-aspiration interval in these four cases was < or = 40 min. PE, 19 (7.3%; 95% CI 4.17-10.51) patients were at risk in the control group compared with 2 (0.7%; 95% CI 0-1.69) in the study group (P < 0.0001). Mean pH in patients receiving omeprazole was significantly higher (P < 0.001) than in the control group. Gastric volumes were significantly lower in the omeprazole group compared with the control group at both PI (P = 0.006) and PE (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "To determine the preventive and therapeutic effect of 10 mg of propofol administered after delivery on the incidence of intraoperative nausea and vomiting (IONV) during intradural anesthesia for cesarean delivery.\n Controlled, randomized double blind study of 60 women (ASA I-II) receiving intradural anesthesia for elective or deferred emergency cesarean delivery. The propofol group received 10 mg i.v. immediately after fetal extraction. The control group received an equal volume of Intralipid. The presence of IONV after administration of the prophylactic bolus was treated with a second bolus, and if nausea had not subsided completely after two minutes, treatment was topped up with dehydro-benzoperidol.\n The control group included 31 women and the propofol group 29, of whom 3 were excluded. Control variables were similar in the two groups. There were no significant differences in the incidence and severity of IONV between the two groups (22.5 versus 23%). The top-up antiemetic drug was used in the same number of patients in each group.\n Although 10 mg propofol has been described as an effective direct antiemetic, episodes of IONV were neither prevented nor reversed by its use during intradural anesthesia for cesarean delivery.", "The efficacy and safety of intravenous metoclopramide administered prophylactically before elective cesarean delivery under spinal anesthesia was studied.\n In a double-blind, randomized fashion, 42 ASA Physical Status I-II parturients at term were assigned to receive either 10-mg intravenous metoclopramide or an equal volume of normal saline before induction of spinal anesthesia. The occurrence of nausea and/or vomiting recorded throughout the perioperative period until the patient was admitted to the recovery room. Neonatal acid-base status and neurobehavioral exams were obtained.\n Patients in the group receiving metoclopramide had a significantly lower incidence of nausea and vomiting both before and after delivery than the control group (14% versus 81% overall). All neonatal acid-base values were within normal limits and there were no significant differences in neurobehavioral exam results between the two groups.\n Metoclopramide administered before induction of spinal anesthesia for cesarean delivery appears to significantly reduce both pre- and postdelivery emetic symptoms without apparent adverse effects on mother or neonate.", "One hundred and sixty-two Chinese women undergoing emergency Caesarean section were allocated at random on admission to the labour ward to receive one of three regimens for orally administered chemoprophylaxis against acid aspiration: ranitidine 150 mg 6 hourly with sodium citrate at induction of anaesthesia, omeprazole 40 mg 12 hourly with sodium citrate, or omeprazole 40 mg 12 hourly alone. Intragastric pH and volume were measured immediately after induction of anaesthesia. Ten patients (17%) in the omeprazole-only group, three (6%) in the omeprazole and citrate group and one (2%) in the ranitidine group had an intragastric pH less than 2.5 and volume greater than 25 ml (p less than 0.05). The use of sodium citrate resulted in higher intragastric pH but larger intragastric volumes (p less than 0.05). The sodium citrate and ranitidine regimen was the most cost-effective among the three.", "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.", "To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery, and to determine whether the inotropes, adrenaline and dopexamine, used to enhance oxygen delivery influence outcome.\n Randomised controlled trial with double blinding between inotrope groups. Setting: York District Hospital, England.\n 138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions. Interventions: Patients were randomised into three groups. Two groups received invasive haemodynamic monitoring, fluid, and either adrenaline or dopexamine to increase oxygen delivery. Inotropic support was continued during surgery and for at least 12 hours afterwards. The third group (control) received routine perioperative care.\n Hospital mortality and morbidity.\n Overall, 3/92 (3%) preoptimised patients died compared with 8/46 controls (17%) (P=0.007). There were no differences in mortality between the treatment groups, but 14/46 (30%) patients in the dopexamine group developed complications compared with 24/46 (52%) patients in the adrenaline group (difference 22%, 95% confidence interval 2% to 41%) and 28 patients (61%) in the control group (31%, 11% to 50%). The use of dopexamine was associated with a decreased length of stay in hospital.\n Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care.", "To determine the effects of thoracic epidural anesthesia (TEA) on ventilation-perfusion (VA/Q) relationships, atelectasis, and oxygenation before and after coronary artery bypass graft surgery (CABG).\n Prospective, controlled, unblinded, randomized trial.\n Cardiothoracic clinic at a major university referral center.\n Twenty-eight patients undergoing elective CABG.\n Perioperative and postoperative TEA was added to general anesthesia (GA) in 14 patients, and 14 patients receiving GA alone served as controls.\n VA/Q relationships were measured by the multiple inert gas elimination technique, and, 20 hours postoperatively, atelectasis was assessed by computerized tomographic scans. Arterial and mixed venous blood gases and hemodynamic variables were measured by standard techniques. TEA per se caused no change in shunt, VA/Q matching, or oxygenation. Induction of GA in the control group and induction of TEA caused similar reductions in mean arterial pressure. The TEA patients needed less morphine analgesia postoperatively and were extubated earlier. Extubation caused significant improvement in VA/Q matching. On the first postoperative day, a slight reduction in PaCO2 was seen in the TEA group, but no differences in shunt, VA/Q matching, or oxygenation compared with the GA group. Both groups showed extensive bilateral atelectasis.\n TEA can reduce respirator time and the need for morphine analgesics after CABG without negative effects on VA/Q matching, oxygenation, or atelectasis formation.", "One hundred and forty-seven patients undergoing elective or emergency Caesarean section under general anaesthesia were allocated randomly to three groups: group 1 (n = 28) received no premedication; group 2 (n = 58) received 0.3-molar sodium citrate 15 ml (sodium citrate 1.16 g); group 3 (n = 61) received effervescent cimetidine-sodium citrate combination (cimetidine 400 mg with sodium citrate 0.9 g) after entering the operating room. Gastric pH was measured at tracheal intubation (pH1) and extubation (pH2). Mean pH1 and mean pH2 values in group 1 were, respectively, 2.25 (SD 1.35) and 2.83 (1.64). Mean pH1 and pH2 values in group 2 were, respectively, 4.38 (1.44) and 4.57 (1.51). In group 3 mean pH1 and pH2 values were, respectively, 5.07 (1.13) and 5.37 (1.30). Percentages of patients with pH1 less than or equal to 2.5 in groups 1, 2 and 3 were, respectively, 75, 13.8 and 1.6. Percentages of patients with pH2 less than or equal to 2.5 in groups 1, 2 and 3 were 50, 10.3 and 1.6, respectively." ]

[ "18091051", "21041710", "16757720", "18459180", "15158627", "18164847", "16446056", "19801201", "2728855" ]

[ "Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases.", "Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study.", "Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial.", "Primary chemotherapy for newly diagnosed nonsmall cell lung cancer patients with synchronous brain metastases compared with whole-brain radiotherapy administered first : result of a randomized pilot study.", "Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial.", "A phase III study of conventional radiation therapy plus thalidomide versus conventional radiation therapy for multiple brain metastases (RTOG 0118).", "Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival.", "Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial.", "Long-term clinical and neurophysiological effects of reconstructive vascular surgery for cerebral ischemia." ]

[ "To determine whether efaproxiral, an allosteric modifier of hemoglobin, improves quality of life and quality of survival in patients with primary breast cancer and brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT).\n Patients with brain metastases from breast cancer were randomly assigned to receive WBRT and either efaproxiral or no efaproxiral. The primary endpoint for this analysis was quality of life and quality-adjusted survival. Quality of life was assessed prior to initiation of WBRT and periodically in follow-up using the Spitzer Quality of Life Index (SQLI).\n A subgroup of 106 eligible breast cancer patients with baseline SQLI were randomized into this study and represent the target population discussed in this report. Treatment, age, and SQLI were significant predictors of survival. The addition of efaproxiral to WBRT reduced the death rate by 46% (P = 0.0086). Quality of life was improved in the WBRT + efaproxiral arm compared with the WBRT alone arm (P = 0.019). Quality-adjusted survival was statistically significantly improved by the addition of efaproxiral to WBRT (P = 0.001).\n Survival, quality of life, and quality-adjusted survival were all improved in breast cancer patients with brain metastases receiving efaproxiral and WBRT compared with those receiving WBRT alone.", "This European Organisation for Research and Treatment of Cancer phase III trial assesses whether adjuvant whole-brain radiotherapy (WBRT) increases the duration of functional independence after surgery or radiosurgery of brain metastases.\n Patients with one to three brain metastases of solid tumors (small-cell lung cancer excluded) with stable systemic disease or asymptomatic primary tumors and WHO performance status (PS) of 0 to 2 were treated with complete surgery or radiosurgery and randomly assigned to adjuvant WBRT (30 Gy in 10 fractions) or observation (OBS). The primary end point was time to WHO PS deterioration to more than 2.\n Of 359 patients, 199 underwent radiosurgery, and 160 underwent surgery. In the radiosurgery group, 100 patients were allocated to OBS, and 99 were allocated to WBRT. After surgery, 79 patients were allocated to OBS, and 81 were allocated to adjuvant WBRT. The median time to WHO PS more than 2 was 10.0 months (95% CI, 8.1 to 11.7 months) after OBS and 9.5 months (95% CI, 7.8 to 11.9 months) after WBRT (P = .71). Overall survival was similar in the WBRT and OBS arms (median, 10.9 v 10.7 months, respectively; P = .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%, P < .001; radiosurgery: 31% to 19%, P = .040) and at new sites (surgery: 42% to 23%, P = .008; radiosurgery: 48% to 33%, P = .023). Salvage therapies were used more frequently after OBS than after WBRT. Intracranial progression caused death in 78 (44%) of 179 patients in the OBS arm and in 50 (28%) of 180 patients in the WBRT arm.\n After radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.", "In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone.\n To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death.\n Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003.\n Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients).\n The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death.\n The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation.\n Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used.\n umin.ac.jp/ctr Identifier: C000000412.", "This randomized pilot trial investigated whether primary chemotherapy was feasible in terms of efficacy, survival, toxicity profile, and quality of life compared with whole-brain radiotherapy (WBRT) given first in chemotherapy-naive patients nonsmall cell lung cancer (NSCLC) with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled by supportive care.\n After stratification by Eastern Cooperative Oncology Group performance status (ECOG PS) (0-1 vs 2), the number of intracranial metastases (<3 vs 3< or =), and the presence of extrathoracic extracranial metastasis, eligible patients were randomized to the primary chemotherapy arm or the WBRT-first arm. World Health Organization (WHO) response criteria, National Cancer Institute Common Toxicity Criteria (NCI-CTC; version 2.0), and the European Organization for Research and Treatment of Cancer (EORTC) C-30/LC-13 questionnaire were used.\n A total of 48 patients were enrolled between August 2002 and November 2005. The response rate of chemotherapy and survival outcomes in the primary chemotherapy arm were not statistically different from those in the WBRT-first arm (overall response rate, 28.0% vs 39.1%; progression-free survival, 3.6 months vs 4.4 months; overall survival, 9.1 months vs 9.9 months). There was close correlation noted between intracranial and extracranial tumor responses (k = 0.82). However, in the WBRT-first arm, grade 3 of 4 neutropenia was more frequent (79% vs 40%) during chemotherapy and 4 patients (17.4%) did not receive further chemotherapy because of early death or poor performance after WBRT. Cognitive function appeared to deteriorate during primary chemotherapy, but was also found to deteriorate after WBRT.\n Primary chemotherapy is more feasible and can be an appropriate option for patients with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled. The role and timing of WBRT should be defined in further studies in this clinical setting.\n (Copyright) 2008 American Cancer Society.", "Brain metastases occur in up to 40% of all patients with systemic cancer. We aimed to assess whether stereotactic radiosurgery provided any therapeutic benefit in a randomised multi-institutional trial directed by the Radiation Therapy Oncology Group (RTOG).\n Patients with one to three newly diagnosed brain metastases were randomly allocated either whole brain radiation therapy (WBRT) or WBRT followed by stereotactic radiosurgery boost. Patients were stratified by number of metastases and status of extracranial disease. Primary outcome was survival; secondary outcomes were tumour response and local rates, overall intracranial recurrence rates, cause of death, and performance measurements.\n From January, 1996, to June, 2001, we enrolled 333 patients from 55 participating RTOG institutions--167 were assigned WBRT and stereotactic radiosurgery and 164 were allocated WBRT alone. Univariate analysis showed that there was a survival advantage in the WBRT and stereotactic radiosurgery group for patients with a single brain metastasis (median survival time 6.5 vs 4.9 months, p=0.0393). Patients in the stereotactic surgery group were more likely to have a stable or improved Karnofsky Performance Status (KPS) score at 6 months' follow-up than were patients allocated WBRT alone (43% vs 27%, respectively; p=0.03). By multivariate analysis, survival improved in patients with an RPA class 1 (p<0.0001) or a favourable histological status (p=0.0121).\n WBRT and stereotactic boost treatment improved functional autonomy (KPS) for all patients and survival for patients with a single unresectable brain metastasis. WBRT and stereotactic radiosurgery should, therefore, be standard treatment for patients with a single unresectable brain metastasis and considered for patients with two or three brain metastases.", "To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery.\n Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines.\n Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects.\n Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.", "To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases.\n Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months.\n Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival.\n The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm.", "It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction.\n Patients with one to three newly diagnosed brain metastases were randomly assigned using a standard permutated block algorithm with random block sizes to SRS plus WBRT or SRS alone from Jan 2, 2001, to Sept 14, 2007. Patients were stratified by recursive partitioning analysis class, number of brain metastases, and radioresistant histology. The randomisation sequence was masked until assignation, at which point both clinicians and patients were made aware of the treatment allocation. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test-Revised (HVLT-R) total recall at 4 months. An independent data monitoring committee monitored the trial using Bayesian statistical methods. Analysis was by intention-to-treat. This trial is registered at www.ClinicalTrials.gov, number NCT00548756.\n After 58 patients were recruited (n=30 in the SRS alone group, n=28 in the SRS plus WBRT group), the trial was stopped by the data monitoring committee according to early stopping rules on the basis that there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function (mean posterior probability of decline 52%) at 4 months than patients assigned to receive SRS alone (mean posterior probability of decline 24%). At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from CNS recurrence at 1 year, compared with 27% of patients who received SRS alone (p=0.0003). In the SRS plus WBRT group, one case of grade 3 toxicity (seizures, motor neuropathy, depressed level of consciousness) was attributed to radiation treatment. In the group that received SRS, one case of grade 3 toxicity (aphasia) was attributed to radiation treatment. Two cases of grade 4 toxicity in the group that received SRS alone were diagnosed as radiation necrosis.\n Patients treated with SRS plus WBRT were at a greater risk of a significant decline in learning and memory function by 4 months compared with the group that received SRS alone. Initial treatment with a combination of SRS and close clinical monitoring is recommended as the preferred treatment strategy to better preserve learning and memory in patients with newly diagnosed brain metastases.", "In a series of patients with unilateral supratentorial ischemia, clinical scores and parameters derived from computer analysis of the EEG and from measurement of the CBF were determined in the first several weeks after the stroke. Seventeen of these patients underwent a carotid-endarterectomy and 15 a STA-MCA bypass operation. Matched control patients were selected from the remaining cases. All patients, including the controls, were eligible for vascular surgery. The measurements were repeated respectively 3 months and 3 years after the first examination. Clinical improvement occurred in all groups. The degree of these clinical changes was similar for operated and non operated cases. EEG changes indicated more improvement in the cases without surgery. Finally, the CBF was remarkably stable in all patients. The overall effects of reconstructive vascular surgery on the recovery after cerebral ischemia appeared to be negligible." ]

[ "3891946", "7612090", "2213261", "1408537", "10730039", "17429240", "17551656", "1297921", "1733156" ]

[ "Randomized trial of prophylactic phototherapy in the infant with very low birth weight.", "Double phototherapy with high irradiance compared with single phototherapy in neonates with hyperbilirubinemia.", "A randomized, controlled application of the Wallaby phototherapy system compared with standard phototherapy.", "Double versus single phototherapy in low birth weight newborns.", "Double versus single phototherapy in term newborns with significant hyperbilirubinemia.", "Fiberoptic, conventional and combination phototherapy for treatment of nonhemolytic hyperbilirubinemia in neonates.", "Efficacy of new microprocessed phototherapy system with five high intensity light emitting diodes (Super LED).", "[A new device for phototherapy of neonatal jaundice].", "A clinical trial of fiberoptic phototherapy vs conventional phototherapy." ]

[ "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.", "The purpose of this study is to compare the effectiveness of double phototherapy versus single conventional phototherapy in decreasing serum bilirubin levels in jaundiced neonates. Forty-two preterm infants who were less than 37 weeks' gestational age and less than 2000 g birthweight with nonhemolytic jaundice were alternately assigned to double phototherapy (n = 19) (Biliblanket, Ohmeda with irradiance of 33 to 35 microW/cm2/nm in addition to single conventional phototherapy with combination of three or four special blue and white lamps with irradiance of 7 to 9 microW/cm2/nm) or to single conventional phototherapy (n = 23) based on elevated serum bilirubin levels in the first week of life. Phototherapy was initiated at specific bilirubin levels in three weight stratifications. The groups were similar in clinical characteristics at study entry. The decrease in serum bilirubin levels was very significant in the double phototherapy group at 8 hours after the therapy (-29 +/- 18.8 versus 8.5 +/- 27 mumol/L; P < 0.001), at 16 hours after the therapy (-49.6 +/- 15.4 versus 3.4 +/- 39 mumol/L; p < 0.001), and at 24 hours after therapy (-71.8 +/- 18.8 versus -3.4 +/- 32.5 mumol/L; p < 0.001) compared with the conventional phototherapy group. The time taken for bilirubin levels to fall below the threshold level was 55 +/- 41 hours in the single group and 14 +/- 6 hours in the double group (p < 0.001). Double phototherapy was well tolerated. The Biliblanket when used in conjunction with single conventional phototherapy resulted in a faster decrease of serum bilirubin.(ABSTRACT TRUNCATED AT 250 WORDS)", "The feasibility and efficacy of a fiberoptic blanket (Wallaby Phototherapy System) for the treatment of physiologic jaundice was compared with conventional phototherapy. Forty-two full-term infants with nonhemolytic jaundice were included in the study. Infants in the study group were treated with the fiberoptic blanket and the infants in the control group were placed under a standard phototherapy unit. Both the fiberoptic blanket and the standard phototherapy unit delivered an average irradiance of 7.0 +/- 0.5 muw/cm2/nm. Incremental changes in serial plasma bilirubin levels compared with the initial bilirubin concentration did not differ between the study and control groups. For infants whose initial plasma bilirubin concentration exceeded 200 mumol/L, a statistically significant difference was found in both study and control groups between the average bilirubin level at initiation of phototherapy and the average bilirubin level at termination of treatment. We conclude that phototherapy delivered by the fiberoptic blanket is safe and has efficacy comparable to that of conventional phototherapy, providing a convenient alternative phototherapy application strategy that obviates the need for eye patches and facilitates maternal handling of the infant during therapy.", "Conventional phototherapy systems that simultaneously irradiate the front and the back of the baby lower the serum bilirubin level more rapidly than one-sided systems, but they are impractical. Fiberoptic phototherapy makes it easy to administer conventional phototherapy from above while the infant lies on a fiberoptic phototherapy blanket. Newborns with birth weights less than 2500 g were randomly assigned to receive either single (n = 37) or double (n = 33) phototherapy. The groups were similar in clinical and laboratory characteristics. After 18 hours of therapy the serum bilirubin concentration declined by 31 +/- 11% in the double and 16 +/- 15% in the single phototherapy group (2.9 +/- 1.1 vs 1.6 +/- 1.4 mg/dL), and the difference in the total serum bilirubin levels after 18 hours of therapy was significant (double phototherapy group 7.1 +/- 2.7 mg/dL vs single phototherapy group 8.2 +/- 2.6 mg/dL). After 18 hours of treatment the serum bilirubin level was less than the phototherapy threshold level in 26 of 37 single phototherapy patients vs 32 of 33 double phototherapy patients. Double phototherapy was well tolerated. It is concluded that this type of double phototherapy is more effective than single phototherapy in low birth weight newborns. Double phototherapy may be useful when it is necessary to reduce an elevated serum bilirubin level as rapidly as possible or when the bilirubin level is rising with single phototherapy.", "The efficacy of double phototherapy, in the form of conventional phototherapy with special blue light plus fiberoptic phototherapy, was compared with conventional phototherapy consisting of special blue lamps alone in a relatively larger series of term newborns with significant hyperbilirubinemia. During the study period the sum of the average spectral irradiances in the double phototherapy group was significantly higher than that of the single phototherapy group (p < 0.05). Phototherapy was effective in decreasing bilirubin levels in both groups, but the response was greater in the double phototherapy group; the duration of exposure to phototherapy was significantly shorter (31.2 +/- 8.5 vs. 38.98 +/- 14.7 h, p < 0.05), and the overall bilirubin decline rate as mumol/l/h and per cent/h was significantly greater in the double phototherapy group (4.1 +/- 1.37 vs. 3.3 +/- 0.86 mumol/l/h, and 1.29 +/- 0.38 vs. 1.02 +/- 0.44 per cent/h, p < 0.05). In phototherapy treatment of term newborns with significant hyperbilirubinemia, double phototherapy provided more rapid and effective bilirubin reduction than conventional phototherapy alone due to higher spectral irradiance and larger body surface area exposed to phototherapy. The value of double phototherapy in the treatment of newborns with hemolytic hyperbilirubinemia remains to be determined.", "The objective of this prospective, randomized study was to compare the effectiveness of fiberoptic, conventional and a combination phototherapy in decreasing bilirubin concentrations in neonatal nonhemolytic hyperbilirubinemia. Forty-six infants who were 36 weeks' gestation and more were randomly assigned to fiberoptic phototherapy (n=16) (Biliblanket, Ohmeda), conventional daylight phototherapy (n=15) and combination phototherapy (n=15) (fiberoptic and conventional). The groups were similar in clinical characteristics at study entry in terms of birth weight, age and bilirubin concentration. There were no statistically significant differences in the duration of treatment among the three groups (P=0.83). There were also no statistically significant differences among the three groups in the serum bilirubin concentrations at 24 hours, 48 hours, end of phototherapy, and 24 hours postphototherapy. We concluded that the decrease in serum bilirubin concentration was comparable among fiberoptic, conventional and combination phototherapy groups.", "To evaluate the efficacy of a microprocessed phototherapy (PT) system with five high intensity light emitting diodes (Super LED) for the treatment of neonatal hyperbilirubinemia of premature infants.\n Randomized clinical trial using Super LED phototherapy in the study group and twin halogen spotlight phototherapy in the control group. A stratified blocked randomization, based on birth weight, was performed. The duration of phototherapy and the rate of decrease of total serum bilirubin (TSB) concentration in the first 24 hours of treatment were the main outcome measures.\n We studied 88 infants, 44 in the Super LED group and 44 in the halogen spotlight PT group. The demographic characteristics of the patients in both groups were similar. Infants in the Super LED group had a similar mean initial serum bilirubin level (10.1+/-2.4 mg%) to those receiving halogen spotlight treatment (10.9+/-2.0 mg%). After 24 hours of treatment, the decrease in total serum bilirubin levels was significantly greater in the Super LED group (27.9 vs. 10.7%, p<0.01) and duration of phototherapy was significantly shorter in this group (36.8 h vs. 63.8 h, p<0.01). After 24 hours of treatment, a significantly greater number of patients receiving Super LED phototherapy had reached serum bilirubin concentrations low enough to allow withdrawal of treatment (23 vs. 10, p<0.01).\n Our results demonstrate that the efficacy of Super LED phototherapy for treating hyperbilirubinemia in premature infants was significantly better than halogen phototherapy.", "The effectiveness of a new device for phototherapy in the treatment of nonhemolytic hyperbilirubinemia (Wallaby Phototherapy System) was evaluated. 46 healthy term infants, appropriate for gestational age and with serum bilirubin > 12 mg/dl in the first 3 days of life or > 15 mg/dl after 3rd day were randomly assigned to a treatment group (24 hours of light exposure with Wallaby Phototherapy System) and to a control group (any treatment for hyperbilirubinemia). Body temperature, weight, feeding and hydration were recorded during the study period. Serum bilirubin and haematocrit were done every 12 hours in all babies. In the treated group we found a decrease of 5.1% and of 7.8% at 12 and 24 hours, while an increase of 3.37% and of 2.9% at 12 and 24 hours was found in the control group. After 24 hours the serum bilirubin level was significantly lower in the treated group than in the control group (p < 0.05). No newborn of the treated group needed conventional phototherapy versus 4 control infants (17.4%). The conclusion of our study is that the Wallaby System is useful in the treatment of neonatal nonhemolytic hyperbilirubinemia even if its effectiveness for higher bilirubin levels has still to be tested.", "We conducted a randomized, controlled trial to compare fiberoptic phototherapy with conventional phototherapy in healthy jaundiced newborns with birth weights greater than 2500 g. Twelve patients received fiberoptic phototherapy and 14 patients received conventional phototherapy. There were no significant differences between the groups with respect to birth weight, gestational age, feeding method, presence of hemolytic disease, hematocrit, reticulocyte count, or initial serum bilirubin level. Measured irradiance at 425 to 475 nm for conventional phototherapy was greater than that of fiberoptic phototherapy (9.2 +/- 0.9 microW/cm2 per nanometer vs 8.2 +/- 1.2 microW/cm2 per nanometer). Both types of phototherapy lowered the level of serum bilirubin after 18 hours of therapy (fiberoptic group, from 231 +/- 29 to 210 +/- 24 mumol/L; conventional group, from 231 +/- 21 to 188 +/- 26 mumol/L), but the mean serum bilirubin level was lower after 18 hours of therapy in the conventional phototherapy group (188 +/- 26 vs 210 +/- 24 mumol/L). There were no side effects in either group of newborns. Both methods of phototherapy decreased the serum bilirubin level, but conventional phototherapy did so more effectively, probably because of its greater irradiance." ]

[ "20037682", "10095821", "9864001", "11001866", "11243949", "14682412", "3902388", "2920584", "2665584" ]

[ "Predictive value and utility of oral steroid testing for treatment of COPD in primary care: the COOPT study.", "The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease.", "An inhaled steroid improves markers of airway inflammation in patients with mild asthma.", "Additive effects of prednisolone and beclomethasone dipropionate in patients with stable chronic obstructive pulmonary disease.", "Systemic glucocorticoids in severe exacerbations of 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 steroid therapy on exercise performance in patients with irreversible chronic obstructive pulmonary disease.", "A randomized controlled trial of methylprednisolone in the emergency treatment of acute exacerbations of COPD.", "High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study." ]

[ "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.", "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.", "Airway inflammation can be demonstrated in mildly asthmatic patients who are not treated with inhaled steroids. Current guidelines recommend that inhaled steroids should be introduced in mild asthmatics who use an inhaled beta2-agonist more than once daily. It was postulated that inhaled steroids can have anti-inflammatory effects in patients with even milder disease. The effect of 4 weeks of treatment with budesonide (800 microg twice daily by Turbohaler) was studied in 10 steroid-naive mildly asthmatic patients (forced expiratory volume in one second (FEV1) = 96+/-1.4% predicted) who required an inhaled beta2-agonist less than one puff daily, in a double-blind, placebo-controlled, crossover fashion. Spirometry, exhaled nitric oxide (NO), bronchial responsiveness (provocative concentration causing a 20% fall in FEV1 (PC20)), and sputum induction were performed before and after each treatment period. Following budesonide treatment, there were significant improvements in FEV1, and PC20, in association with a significant reduction in the percentage of eosinophils in induced sputum. Exhaled NO levels tended towards reduction, but the change was nonsignificant. There were also nonsignificant reductions in sputum eosinophil cationic protein and tumour necrosis factor-alpha levels. In conclusion inhaled budesonide can lead to improvements in noninvasive markers of airway inflammation, in association with a small improvement in lung function, even in mildly asthmatic patients who require an inhaled beta2-agonist less than once daily. This suggests a potential benefit of inhaled corticosteroids, even in relatively asymptomatic asthma.", "It remains unclear whether inhaled corticosteroids can produce the maximum benefits of corticosteroids in patients with chronic obstructive pulmonary disease (COPD). To assess the additive effects of 30 mg/day prednisolone to high-dose, inhaled beclomethasone dipropionate (BDP), we conducted a randomised double-blind, placebo-controlled cross-over trial. The study population consisted of 21 men with stable COPD. The mean age of the patients was 69.1 +/- 6.8 years, and FEV(1)was 0.86 +/- 0.28 l. Seventeen out of the 21 patients (81%) were considered susceptible to steroids in a previous trial (FEV(1)increased at least 15% from baseline after receiving 14 days of 30 mg/day prednisolone). All of the patients had been on 1600 microg/day BDP for more than 3 months. Spirometry was performed before the entry, and at the end of 3-week placebo and prednisolone periods. The peak expiratory flow (PEF), symptoms, and Guyatt's Chronic Respiratory Disease Questionnaire (CRQ) as a disease specific health-related quality of life over the last seven days of each period were also evaluated. Although a marginal increase in PEF was found during the prednisolone period, no significant differences in FEV(1), FVC, symptoms or CRQ scores were observed between the two treatment periods. We conclude that the therapeutic effects of steroid therapy may be achieved by the long-term use of high-dose, inhaled corticosteroid in some patients with stable COPD.\n Copyright 2000 Academic Press.", "This study aimed to compare the efficacies of 3-day and 10-day courses of methylprednisolone (MP) treatment in severe COPD exacerbations necessitating hospitalization for respiratory failure.\n Prospective, randomized, single-blind study.\n Tertiary-care center.\n Thirty-six patients were included in the study and randomized into two groups: group 1 received MP, 0.5 mg/kg q6h for 3 days, and group 2 was administered the same dosage of MP for the first 3 days, after which it was tapered and terminated on the tenth day. There was no difference between the groups for age, baseline FEV(1), PaO(2), PaCO(2), and pH levels. One patient in group 1 who developed pneumothorax and one patient in group 2 who had steroid-related psychosis could not complete the study.\n Both groups showed significant improvements in PaO(2) and FEV(1) levels, but these were more marked in group 2 (p = 0.012 and p = 0.019, respectively). There was a significant increase in FVC levels in group 2 only (p = 0.003). Group 2 also had a more marked improvement in dyspnea on exertion. There was no difference between the two groups with regards to other parameters, including pH, PaCO(2) levels, and other symptom scores. Six patients in group 1 and five patients in group 2 developed new exacerbations within the following 6 months. Hyperglycemia occurred in two patients in each group.\n In severe COPD exacerbations, a 10-day course of steroid treatment is more effective than a 3-day course in improving the outcome, but has no benefit in reducing exacerbation rates.", "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.", "Many patients with irreversible chronic obstructive pulmonary disease (COPD) claim symptomatic improvement with steroid therapy, despite a lack of objective improvement in their spirometric data. To determine if steroids actually increase the exercise capacity of these individuals, 13 clinically stable patients (mean age, 63 +/- 4 years; 12 male patients) were given methylprednisolone (32 mg once daily) or placebo in a randomized double-blind crossover fashion. Spirometric data and minute ventilation, oxygen consumption (VO2), carbon dioxide production, and heart rate during incremental exercise were measured at each visit. Methylprednisolone did not produce a significant change in any of the measured parameters. Three patients had an increase in maximal VO2 of greater than 2 ml/kg/min during therapy with methylprednisolone, while two experienced a decline in maximal VO2 of similar magnitude. The change in exercise capacity was unrelated to the change in the forced expiratory volume in one second in individual patients (r = 0.08). We conclude that in the absence of any improvement in the usual tests of airway mechanics, steroid therapy does not improve exercise performance in patients with COPD.", "We conducted a randomized, controlled double-blind study to determine whether intravenous administration of methylprednisolone early in the therapy for acute exacerbations of COPD would improve pulmonary function in the Emergency Department and reduce the need for hospitalization. Ninety-six patients completed the study. All were at least 50 years of age and had no history of asthma. Patients received aminophylline and hourly administration of aerosolized isoetharine. Methylprednisolone (100 mg) or physiologic saline solution was given within one-half hour of arrival in the Emergency Department. Spirometry was performed initially and after the third and fifth aerosol treatments. We found no greater improvement in FEV1 in the group receiving the steroid (37 percent) than in the control group (43 percent; NS). There was also no difference in the rate of hospitalization (33 percent in the steroid-treated group vs 30 percent in the control group; NS). We conclude that early administration of methylprednisolone does not affect the emergency phase of treatment for acute exacerbations of COPD.", "In a multicenter, randomized, double-blind study, inhaled beclomethasone dipropionate (BDP) 1,500 micrograms/day was compared to placebo in 43 chronic asthmatic patients uncontrolled by inhaled salbutamol and oral theophylline. During the prestudy period, a test of maximal steroid reversibility with oral prednisolone 0.5 mg/kg/day for 14 days was performed. The therapeutic response was measured over an 8-wk period as the ability to maintain the clinical improvement and the optimal pulmonary function induced by prednisolone. During the study, severe asthma exacerbation occurred in one (5%) of the 21 patients who received BDP and in 15 (78%) of the 22 patients who received placebo (p less than 0.001). In patients who received BDP, FEV1 and peak expiratory flow (PEF) remained above the optimal postprednisolone value, with a trend to improvement during the 8-wk study period. In patients who received placebo, FEV1 and PEF decreased and remained below the optimal value. We conclude that, in chronic asthma, inhaled BDP 1,500 micrograms/day maintains the optimal pulmonary function in addition to the clinical benefit induced by a short course of oral corticosteroids." ]

[ "2358916", "3524234", "9215204", "2372330", "10642968", "3904818", "8169910", "10841126", "9875920" ]

[ "Vibroacoustic stimulation and fetal heart rate in nonstress tests.", "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.", "Effect of vibratory acoustic stimulation on the duration of fetal heart rate monitoring tests.", "The predictive value of fetal acoustic stimulation.", "Non-stress antenatal cardiotocography--a prospective randomized clinical trial.", "Comparison of the acoustic stimulation test with nonstress test. A randomized, controlled clinical trial.", "Cardiotocography only versus cardiotocography plus PR-interval analysis in intrapartum surveillance: a randomised, multicentre trial. FECG Study Group.", "A randomized, controlled trial of computerized physiologic trend monitoring in an intensive care unit." ]

[ "Two methods of vibroacoustic stimulation were compared with traditional nonstress tests. Fetal heart rate tracings following stimulation had more accelerations and were of greater amplitude and duration than in the control group. The length of time required to obtain a reactive nonstress test was almost 15 minutes shorter when vibroacoustic stimulation was applied than when vibroacoustic stimulation was not used. Vibroacoustic stimulation elicited a heightened reactivity that persisted beyond the observation period in 30 of 45 (67%) of the experimental group subjects.", "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.", "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.", "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.", "A randomized controlled trial examined the effects of non-stress antepartum cardiotocography on obstetric management and assessed its usefulness as a diagnostic test of fetal compromise. Daily cardiotocograph recordings were made in 396 antenatal patients at increased risk of fetal compromise but were withheld from the clinicians responsible for care in half the cases. The frequency of intrapartum fetal distress and low Apgar score was similar in the two groups. The three normally-formed perinatal deaths all occurred in the revealed group but in only one case could earlier obstetric intervention have altered the outcome. Availability of non-stress cardiotocography was not associated with an increased rate of induction of labour or caesarean section.", "The nonstress test (NST) is a helpful adjunct in the management of high-risk pregnancies. It has high predictability and a low false-negative rate but unfortunately has fairly high false-positive results. Attempts have been made to find a suitable stimulant to help decrease nonreactive results as well as to shorten the duration of testing: the recently introduced fetal acoustic stimulation test (AST) may have such attributes. This prospective, randomized clinical trial was carried out to assess the new test. A total of 1,300 individual tests were performed on high-risk pregnancies. Cases were randomized to receive either the AST or NST. All tracings were interpreted blindly by an independent perinatologist. The incidence of nonreactive tests was 6.8% in the AST group and 13.8% in the NST group (P < .001). There was a significant reduction in the time needed for a reactive test to occur. It can be concluded, therefore, that AST offers a greater advantage over NST by lowering both the incidence of nonreactive tests and testing time, thereby resulting in less of a need for the contraction stress test and biophysical profile.", "There is a need to improve the sensitivity and specificity of fetal monitoring during labour. We compared the gold standard, cardiotocography, with cardiotocography plus time-interval analysis of the fetal electrocardiogram in fetal surveillance. The aim was to find out whether time-interval analysis decreased the need for operative intervention due to fetal distress.\n We did a randomised, prospective trial in five hospitals in the UK, Hong Kong, the Netherlands, and Singapore. 1038 women undergoing high-risk labours were randomly assigned fetal monitoring by cardiotocography alone, or cardiotocography plus fetal electrocardiography (ECG). Outcomes measured were rates of operative intervention, and neonatal outcome. Analysis was by intention to treat.\n 515 women were assigned management by cardiotocography, and 523 cardiotocography plus fetal ECG. There was a trend towards fewer operative interventions for presumed fetal distress in the time-interval analysis plus cardiotocography group (63 [13%] vs 78 [16%]), but this was not significant (relative risk 0.80 [95% CI 0.59-1.08], p=0.17). There was no significant difference between groups in the proportion of babies who had an umbilical arterial pH of 7.15 or less (51 [11%] vs 49 [11%]; 1.01 [0.7-1.47]), or in the frequency of unsuspected acidaemia (42 [9%] vs 35 [8%]; 1.17 [0.76-1.79]).\n The addition of time-interval analysis of the fetal electrocardiogram during labour did not show a significant benefit in decreasing operative intervention. There was no significant difference in neonatal outcome.", "To assess whether the provision of computerized physiologic trend data could improve outcome in newborn infants requiring intensive care.\n Randomized, controlled trial, with subsidiary questionnaire studies.\n Tertiary neonatal intensive care unit with 12 intensive care cots.\n All infants admitted between January 1991 and September 1993 who were < or =32 wks gestation or >32 wks gestation, and ventilated for >4 hrs or asphyxiated.\n Randomization to one of four groups for first 7 days of life: A) no display of trend data; B) continuous display of trend data; C1) alternating 24-hr display of trend data, starting with display in first 24 hrs; and C2) alternating 24-hr display of trend data, starting with no display in first 24 hrs.\n The short-term effects of monitoring on patient outcome was judged by volume of colloid given, number of blood gases taken, and by measurement taken from cranial Doppler ultrasound. Medium-term measures included time ventilated, time given supplemental oxygen, death, time to death or discharge, and cranial ultrasound at discharge. Long-term outcome was assessed by neurodevelopmental status at age 1 to 4 yrs of age. Staff and parent questionnaires assessed their respective attitudes to the introduction of this technology. None of the patient outcome measures, short-, medium-, or long-term, demonstrated any significant benefit from the provision of computerized physiologic trend monitoring. Staff questionnaires demonstrated an acceptance of the system and an improved understanding of neonatal physiology as a result of computerized physiologic trends. Parent questionnaires demonstrated increased anxiety caused by the system in 11% of parents, although only 1% of parents continued to have concerns if the system were able to help their child.\n A randomized, controlled trial was unable to demonstrate any benefit to patients resulting from the introduction of a computerized physiologic trend monitoring system. Benefits of the system have been recognized, however, in subsidiary studies, staff education, and research studies." ]

[ "19809023", "15629973", "18829790", "16061595", "21245887", "12169832", "21633770", "7996367", "16126048" ]

[ "Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial.", "Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants.", "Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial.", "Randomized trial of donor human milk versus preterm formula as substitutes for mothers' own milk in the feeding of extremely premature infants.", "Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial.", "Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study.", "A randomised controlled trial of glutamine-enriched neonatal parenteral nutrition in Malaysia.", "Intravenous immune globulin prophylaxis of late-onset sepsis in premature neonates.", "Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates." ]

[ "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.", "We evaluated the efficacy of probiotics in reducing the incidence and severity of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants.\n A prospective, masked, randomized control trial was conducted to evaluate the beneficial effects of probiotics in reducing the incidence and severity of NEC among VLBW (<1500 g) infants. VLBW infants who started to fed enterally and survived beyond the seventh day after birth were eligible for the trial. They were randomized into 2 groups after parental informed consents were obtained. The infants in the study group were fed with Infloran (Lactobacillus acidophilus and Bifidobacterium infantis) with breast milk twice daily until discharged. Infants in the control group were fed with breast milk alone. The clinicians caring for the infants were blinded to the group assignment. The primary outcome was death or NEC (>or= stage 2).\n Three hundred sixty-seven infants were enrolled: 180 in the study group and 187 in the control group. The demographic and clinical variables were similar in both groups. The incidence of death or NEC (>or= stage 2) was significantly lower in the study group (9 of 180 vs 24 of 187). The incidence of NEC (>or= stage 2) was also significantly lower in the study when compared with the control group (2 of 180 vs 10 of 187). There were 6 cases of severe NEC (Bell stage 3) in the control group and none in the study group. None of the positive blood culture grew Lactobacillus or Bifidobacterium species.\n Infloran as probiotics fed enterally with breast milk reduces the incidence and severity of NEC in VLBW infants.", "The goal was to investigate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis for very low birth weight preterm infants.\n A prospective, blinded, randomized, multicenter controlled trial was conducted at 7 NICUs in Taiwan, to evaluate the beneficial effects of probiotics in necrotizing enterocolitis among very low birth weight infants (birth weight: <1500 g). Very low birth weight infants who survived to start enteral feeding were eligible and were assigned randomly to 2 groups after parental informed consent was obtained. Infants in the study group were given Bifidobacterium bifidum and Lactobacillus acidophilus, added to breast milk or mixed feeding (breast milk and formula), twice daily for 6 weeks. Infants in the control group were fed with breast milk or mixed feeding. The clinicians caring for the infants were blinded to the group assignment. The primary outcome measurement was death or necrotizing enterocolitis (Bell's stage >or=2).\n Four hundred thirty-four infants were enrolled, 217 in the study group and 217 in the control group. The incidence of death or necrotizing enterocolitis (stage >or=2) was significantly lower in the study group (4 of 217 infants vs 20 of 217 infants). The incidence of necrotizing enterocolitis (stage >or=2) was lower in the study group, compared with the control group (4 of 217 infants vs 14 of 217 infants). No adverse effect, such as sepsis, flatulence, or diarrhea, was noted.\n Probiotics, in the form of Bifidobacterium and Lactobacillus, fed enterally to very low birth weight preterm infants for 6 weeks reduced the incidence of death or necrotizing enterocolitis.", "Compared with preterm formula (PF), mother's milk (MM) is associated with lower rates of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) among premature infants. Because not all mothers of premature infants produce sufficient milk to supply their infants throughout hospitalization, we reasoned that pasteurized donor human milk (DM) would be a suitable alternative.\n Extremely premature infants (<30 weeks of gestation) whose mothers intended to breastfeed were assigned randomly to receive either pasteurized DM or PF if the supply of their own MM became insufficient during the study (birth to 90 days of age or hospital discharge). Infection-related events (LOS, NEC, meningitis, presumed sepsis, or urinary tract infection) that occurred after the attainment of a milk intake of 50 mL/kg, dietary intake, growth, skin-to-skin contact, and duration of hospital stay were compared. The primary analysis compared groups DM and PF on an intent-to-treat basis. If no differences were noted, then these groups were combined and compared with the reference group, group MM. If differences were noted, then the subsequent analyses compared each group with group MM.\n Of 243 infants, 70 (29%) received only MM; group DM included 81 infants and group PF included 92 infants. Because of poor weight gain, 17 infants (21%), all in group DM, were switched to PF. There were no differences in birth weight, gestational age, multiple births, and age at attainment of feeding of 50 mL/kg among groups. There were no differences between group DM and group PF in LOS and/or NEC, other infection-related events, hospital stay, or number of deaths. Group DM received a greater intake of milk and more nutritional supplements but had a slower rate of weight gain, compared with group PF. Compared with groups DM and PF, group MM had fewer episodes of LOS and/or NEC and total infection-related events and a shorter duration of hospital stay. Group MM also had fewer Gram-negative organisms isolated from blood cultures than did the other groups.\n In this randomized, blinded trial of feeding of extremely premature infants, we found that, as a substitute for MM, DM offered little observed short-term advantage over PF for feeding extremely premature infants. Advantages to an exclusive diet of MM were observed in terms of fewer infection-related events and shorter hospital stays.", "The identification of probiotic species involved in gut homeostasis and their potential therapeutic benefits have led to an interest in their use for preventing necrotizing enterocolitis (NEC). Although bifidobacterium and lactobacilli sp. have been used to reduce the incidence of NEC in clinical trials. Lactobacillus sporogenes has not been used in the prevention of NEC in very low-birth weight infants yet. The objective of this study was to evaluate the efficacy of orally administered L sporogenes in reducing the incidence and severity of NEC in very low-birth weight (VLBW) infants.\n A prospective, blinded, randomized controlled trial was conducted in preterm infants with a gestational age of <33 weeks or birth weight of <1500 g. VLBW infants who survived to start enteral feeding were randomized into two groups The infants in the study group were given L. sporogenes with a dose of 350,000,000 c.f.u. added to breast milk or formula, once a day, starting with the first feed until discharged. The infants in the control group were fed without L. sporogenes supplementation. The primary outcome measurement was death or NEC (Bell's stage ≥2).\n A total of 221 infants were studied: 110 in the study group and 111 in the control group. There was no significant difference in the incidence of death or NEC between the groups. Feeding intolerance was significantly lower in the probiotics group than in the control group (44.5% (n: 49) vs 63.1% (n: 70), respectively; P=0.006).\n L. sporogenes supplementation at the dose of 350,000,000 c.f.u/day is not effective in reducing the incidence of death or NEC in VLBW infants, however, it could improve the feeding tolerance.\n © 2011 Macmillan Publishers Limited All rights reserved", "It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units (NICUs). The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections (UTIs), bacterial sepsis and necrotizing enterocolitis (NEC) in preterm infants.\n A double-blind study was conducted in 12 Italian NICUs. Newborn infants with a gestational age <33 weeks or birthweight <1,500 g were randomized to receive standard milk feed supplemented with Lactobacillus GG (Dicoflor), Dicofarm, Rome, Italy) in a dose of 6 x 10(9) colony-forming units (cfu) once a day until discharge, starting with the first feed or placebo.\n Five hundred eighty-five patients were studied. The probiotics group (n = 295) and the placebo group (n = 290) exhibited similar clinical characteristics. The duration of Lactobacillus GG and placebo supplementation was 47.3 +/- 26.0 and 48.2 +/- 24.3 days, respectively. Although UTIs (3.4 vs. 5.8%) and NEC (1.4 vs. 2.7%) were found less frequently in the probiotic group compared to the control group, these differences were not significant. Bacterial sepsis was more frequent in the probiotics group (4.4%, n = 11) than in the placebo group (3.8%, n = 9), but the difference was not significant.\n Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs, NEC and sepsis in preterm infants. Further studies are required to confirm our results in lower birthweight populations.\n Copyright 2002 S. Karger AG, Basel", "The addition of glutamine to parenteral nutrition (PN) in neonates has not shown significant benefits as compared to adults thus far. This study aimed to determine the potential benefits of the addition of glutamine to neonatal PN in a tertiary hospital in a middle-income country.\n This was a double-blinded randomised controlled trial. Babies who were admitted to the neonatal intensive care unit (NICU) and who required PN were eligible for inclusion in the study. The subjects were randomised to receive either glutamine-added PN (intervention) or standard PN (control). The most important outcomes included time to full enteral nutrition, incidence of sepsis and necrotising enterocolitis (NEC), clinical or culture-proven sepsis.\n Out of 270 subjects, 132 were randomised to the intervention group and 138, to the control group. Baseline data were comparable in both groups. The median time taken to reach full enteral nutrition was similar for both intervention and control groups (six days in each group, p-value is 0.52). The incidences of NEC, clinical sepsis and culture-proven sepsis did not differ significantly in the intervention and control groups (5.8 vs. 7.1 percent, p-value is 0.68; 15.7 percent vs. 10.2 percent, p-value is 0.21 and 16.5 percent vs. 15.7 percent, p-value is 0.38, respectively). Other outcomes such as duration of ventilation, duration of NICU stay and a subgroup analysis for preterm and term babies also showed no statistically significant differences.\n Addition of glutamine to neonatal PN was not shown to improve outcome.", "To determine whether a single dose of intravenously administered immune globulin (IVIG) decreases late-onset sepsis in premature infants, we prospectively entered 753 neonates with birth weight 500 to 2000 gm, gestation < or = 34 weeks, and age < or = 12 hours into a multicenter, double-blind, controlled trial. Infants were randomly selected to receive a single intravenous infusion, 10 ml/kg, of either IVIG (500 mg/kg) or albumin (5 mg/kg) and were observed for 8 weeks for infection. Maternal and neonatal risk factors for infection did not differ between groups. Although serum IgG values before infusion were related to gestation (R = 0.62), the change in serum IgG or half-life of IgG after IVIG infusion was not (R < or = 0.09). The serum IgG concentration was increased (p < 0.05) in IVIG-treated patients for 8 weeks. There were 88 episodes of late-onset sepsis in 79 neonates (10.5%). Causative organisms included the following: Staphylococcus epidermidis (37 episodes), Enterococcus (9), Staphylococcus aureus (7), Candida (6), Escherichia coli (6), and multiple organisms (11). Sepsis, death, and death as a result of infection were unaffected by treatment. We conclude that a single infusion of IVIG, 500 mg/kg, shortly after birth was not effective prophylaxis for late-onset infection in premature neonates. Future studies of late-onset sepsis prophylaxis should consider IVIG with known pathogen-specific antibody concentrations against organisms causing these infections, in particular S. epidermidis.", "To test the hypothesis that normalizing the intestinal flora by administration of prophylactic probiotics would provide a natural defense, thereby reducing both the incidence and severity of necrotizing enterocolitis (NEC) in preterm neonates.\n Neonates < or =1500 g birth weight were randomized to either receive a daily feeding supplementation with a probiotic mixture (Bifidobacteria infantis, Streptococcus thermophilus, and Bifidobacteria bifidus; Solgar, Israel) of 10(9) colony forming units (CFU)/day or to not receive feed supplements. NEC was graded according to Bell's criteria.\n For 72 study and 73 control infants, respectively, birth weight (1152 +/- 262 g vs 1111 +/- 278 g), gestational age (30 +/- 3 weeks vs 29 +/- 4 weeks), and time to reach full feeds (14.6 +/- 8.7 days vs 17.5 +/- 13.6 days) were not different. The incidence of NEC was reduced in the study group (4% vs 16.4%; P=.03). NEC was less severe in the probiotic-supplemented infants (Bell's criteria 2.3 +/- 0.5 vs 1.3 +/- 0.5; P=.005). Three of 15 babies who developed NEC died, and all NEC-related deaths occurred in control infants.\n Probiotic supplementation reduced both the incidence and severity of NEC in our premature neonatal population." ]

[ "9033441", "11044540", "2866047", "14678373", "35296", "15077078", "26371", "16291357", "11597664" ]

[ "Short-term regular beta 2-adrenergic agonists treatment is safe in mild asthmatics taking low doses of inhaled steroids.", "beta(2)-adrenergic agonists and pelvic floor exercises for female stress incontinence.", "Effect of beta-adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease.", "A randomized crossover study to evaluate Ro 115-1240, a selective alpha1A/1L-adrenoceptor partial agonist in women with stress urinary incontinence.", "Selectivity of beta adrenoreceptor antagonist drugs assessed by histamine bronchial provocation.", "A comparison between oral antiarrhythmic drugs in the prevention of atrial fibrillation after cardiac surgery: the pilot study of prevention of postoperative atrial fibrillation (SPPAF), a randomized, placebo-controlled trial.", "A comparison of four beta-adrenoceptor antagonists in patients with asthma.", "Clinical impact of corticosteroid-induced adrenal suppression during treatment for acute lymphoblastic leukemia in children: a prospective observational study using the low-dose adrenocorticotropin test.", "Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study." ]

[ "Regular treatment with beta 2-adrenergic agonists is controversial in bronchial asthma. To investigate whether beta 2-adrenergic agonists can be used safely if associated with low doses of inhaled steroids, for a short period, without a deterioration of asthma control, we have examined 24 mild asthmatics. In a parallel, double-blind, placebo-controlled study, 1 week of run-in and run-out period framed 3 weeks of treatment. All patients received inhaled beclomethasone dipropionate (BDP 250 micrograms t.i.d.); after 1 week, 12 patients inhaled 400 micrograms of broxaterol and 12 patients received placebo t.i.d. FVC, FEV1, PD20-FEV1 methacholine, morning and evening PEF, and PEF amplitude % mean were measured before, during, and after treatment. No significant changes were noted in patients receiving inhaled broxaterol. There were no differences in symptoms and the use of rescue medication (salbutamol spray). We conclude that short-term regular treatment with beta 2-adrenergic agonists is not associated with a deterioration in asthma control in mild asthmatics inhaling low doses of steroids.", "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.", "Beta-Adrenergic blockers have not been widely used in patients with peripheral vascular disease because these drugs have been reported to worsen the symptoms of intermittent claudication. To test this assumption we studied the effects of a beta 1-selective and a nonselective beta-adrenergic blocker on postexercise calf blood flow and symptoms of claudication in 19 patients with mild-to-moderate peripheral vascular disease. Subjects received placebo for 3 weeks, and then were randomized to 120 mg/day propranolol or 150 mg/day metoprolol with the use of a crossover design. Blood flow in the calf was measured by strain-gauge plethysmography at rest and immediately after exercise on a bicycle ergometer at a low and a high workload. The symptoms of claudication were monitored during bicycle exercise and by patient diaries maintained between visits. Maximal exercise heart rate was reduced an equivalent amount by metoprolol (19 beats/min) and propranolol (16 beats/min). Mean arterial pressure was reduced by propranolol at rest and by both drugs with exercise. Calf blood flow was not affected by either drug compared with placebo at rest or at either workload. In addition, the symptoms of claudication were not worsened by either drug. We conclude that despite evidence of beta 1-adrenergic blockade and a lowering of arterial pressure, neither beta-adrenergic blocker adversely affected the peripheral circulation.", "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.", "In a double-blind, within-patient, randomized study, 12 mild asthmatics were given single oral doses of propranolol (80 mg), metoprolol (100 mg), timolol (10 mg), or placebo. Resting heart rate and forced expiratory volume in one sec (FEV1) were measured before and 90 min after treatment. Nonspecific bronchial reactivity was measured by inhaled histamine at 90 min. Following each active drug, resting heart rate changed to a similar extent and to a greater degree than after placebo (p less than 0.01). Changes in FEV1 were small and not different from those after placebo. In contrast, after each active drug, bronchial reactivity increased more than after placebo. The degree of reactivity with each active drug was similar but the differences from corresponding placebo values were significant (p less than 0.05). We conclude that, in mild asthmatics, nonspecific bronchial reactivity is a more sensitive index of airway effects than resting FEV1. Moreover, in the context of this study, since the beta-blockers were given in doses likely to induce equivalent cardiac beta-blockade, there is no evidence to suggest that any one of them is more \"cardioselective\" than the others.", "Atrial fibrillation (AF) frequently occurs after cardiac surgical procedures, and beta-blockers, sotalol, and amiodarone may reduce the frequency of AF after open heart surgery. This pilot trial was designed to test whether each of the active oral drug regimens is superior to placebo for prevention of postoperative AF and whether there are differences in favor of 1 of the preventive strategies.\n We conducted a randomized, double-blinded, placebo-controlled trial in which patients undergoing cardiac surgery in the absence of heart failure and without significant left ventricular dysfunction (n = 253; average age, 65 +/- 11 years) received oral amiodarone plus metoprolol (n = 63), metoprolol alone (n = 62), sotalol (n = 63), or placebo (n = 65). Patients receiving combination therapy (amiodarone plus metoprolol) and those receiving sotalol had a significantly lower frequency of AF (30.2% and 31.7%; absolute difference, 23.6% and 22.1%; odds ratios [OR], 0.37 [95% CI, 0.18 to 0.77, P <.01 vs placebo] and 0.40 [0.19 to 0.82, P =.01 vs placebo]) compared with patients receiving placebo (53.8%). Treatment with metoprolol was associated with a 13.5% absolute reduction of AF (P =.16; OR, 0.58 [0.29 to 1.17]. Treatment effects did not differ significantly between active drug groups. Adverse events including cerebrovascular accident, postoperative ventricular tachycardia, nausea, and dyspepsia, in hospital death, postoperative infections, and hypotension, were similar among the groups. Bradycardia necessitating dose reduction or drug withdrawal occurred in 3.1% (placebo), 3.2% (combined amiodarone and metoprolol; P =.65 vs placebo), 12.7% (sotalol; P <.05 vs placebo), and 16.1% (metoprolol; P <.05 vs placebo). Patients in the placebo group had a nonsignificantly longer length of hospital stay as compared with the active treatment groups (13.1 +/- 8.9 days vs 11.3 +/- 7; P =.10), with no significant difference between the active treatment groups.\n Oral active prophylaxis with either sotalol or amiodarone plus metoprolol may reduce the rate of AF after cardiac surgery in a population at high risk for postoperative AF. Treatment with metoprolol alone resulted in a trend to a lower risk for postoperative AF.", "1 Cardiovascular and airways response to two non-cardioselective beta-adrenoceptor blocking drugs, propranolol and pindolol (with partial agonist activity) and two cardioselective beta-adrenoceptor blocking drugs, acebutolol (with partial agonist activity) and atenolol, were compared in twelve patients with asthma. 2 All four drugs produced a significant reduction in resting pulse rate and prevented the increase in heart rate following inhaled isoprenaline (1,500 microgram). 3 Seven patients in clinical remission showed no significant bronchoconstrictor response to any of the drugs. In the remaining five patients, bronchoconstriction was greatest following propranolol (mean reduction in FEV1 26.6%) and least following atenolol (mean reduction in FEV1 6.5%). 4 The bronchodilator response to inhaled isoprenaline was blocked by propranolol and pindolol but not by acebutolol and atenolol. 5 Partial agonist activity did not appear to be clinically useful.", "To investigate how frequently adrenal function fails to recover after corticosteroid therapy in children with acute lymphoblastic leukemia and to explore the clinical impact of slow adrenal recovery without steroid substitution.\n Low-dose (1 microg) adrenocorticotropic hormone tests were performed before and after steroid courses and during infectious episodes in 24 children. Test results were not available during the study.\n All 13 patients tested before treatment had normal adrenal responses. Adrenal suppression was found in 8 (47%) of 17 patients 5 days after discontinuation of a 5-week induction course of prednisolone and in 1 (20%) of 5 patients 7 days after a 3-week intensification course of dexamethasone, both courses being tapered over 9 days, as well as in all 13 patients tested 2 days after a 1-week prednisolone course. Clinically significant manifestations of adrenal suppression were noted in 3 (12%) patients. Of 204 scheduled tests, 131 were performed.\n High-dose glucocorticoid therapy may cause adrenal suppression lasting more than 1 week in children with acute lymphoblastic leukemia, even after tapering the dose. We suggest steroid replacement during stress episodes within 1 to 2 weeks after discontinuation and thereafter testing adrenal function selectively in accordance with symptoms.", "Endothelin 1, a powerful endogenous vasoconstrictor and mitogen, might be a cause of pulmonary hypertension. We describe the efficacy and safety of bosentan, a dual endothelin-receptor antagonist that can be taken orally, in patients with severe pulmonary hypertension.\n In this double-blind, placebo-controlled study, 32 patients with pulmonary hypertension (primary or associated with scleroderma) were randomly assigned to bosentan (62.5mg taken twice daily for 4 weeks then 125 mg twice daily) or placebo for a minimum of 12 weeks. The primary endpoint was change in exercise capacity. Secondary endpoints included changes in cardiopulmonary haemodynamics, Borg dyspnoea index, WHO functional class, and withdrawal due to clinical worsening. Analysis was by intention to treat.\n In patients given bosentan, the distance walked in 6 min improved by 70 m at 12 weeks compared with baseline, whereas it worsened by 6 m in those on placebo (difference 76 m [95% CI 12-139], p=0.021). The improvement was maintained for at least 20 weeks. The cardiac index was 1.0 L min(-1) m(-2) (95% CI 0.6-1.4, p<0.0001) greater in patients given bosentan than in those given placebo. Pulmonary vascular resistance decreased by 223 dyn s cm(-)(5) with bosentan, but increased by 191 dyn s cm(-5) with placebo (difference -415 [-608 to -221], p=0.0002). Patients given bosentan had a reduced Borg dyspnoea index and an improved WHO functional class. All three withdrawals from clinical worsening were in the placebo group (p=0.033). The number and nature of adverse events did not differ between the two groups.\n Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension, suggesting that endothelin has an important role in pulmonary hypertension." ]

[ "16893677", "15249261", "15762903", "15802479", "14687254", "12757433", "10193883", "11759464", "15360790" ]

[ "What factors are associated with the integration of evidence retrieval technology into routine general practice settings?", "Providing a web-based online medical record with electronic communication capabilities to patients with congestive heart failure: randomized trial.", "Can computer-generated evidence-based care suggestions enhance evidence-based management of asthma and chronic obstructive pulmonary disease? A randomized, controlled trial.", "A randomized trial of electronic clinical reminders to improve quality of care for diabetes and coronary artery disease.", "Effects of computerized guidelines for managing heart disease in primary care.", "Educational workshop improved information-seeking skills, knowledge, attitudes and the search outcome of hospital clinicians: a randomised controlled trial.", "Shared care for diabetes: supporting communication between primary and secondary care.", "General practitioners and hospitals. Continuity of care.", "Effectiveness of an electronic medical record clinical quality alert prepared by off-line data analysis." ]

[ "Information retrieval systems have the potential to improve patient care but little is known about the variables which influence clinicians' uptake and use of systems in routine work.\n To determine which factors influenced use of an online evidence retrieval system.\n Computer logs and pre- and post-system survey analysis of a 4-week clinical trial of the Quick Clinical online evidence system involving 227 general practitioners across Australia.\n Online evidence use was not linked to general practice training or clinical experience but female clinicians conducted more searches than their male counterparts (mean use=14.38 searches, S.D.=11.68 versus mean use=8.50 searches, S.D.=9.99; t=2.67, d.f.=157, P=0.008). Practice characteristics such as hours worked, type and geographic location of clinic were not associated with search activity. Information seeking was also not related to participants' perceived information needs, computer skills, training nor Internet connection speed. Clinicians who reported direct improvements in patient care as a result of system use had significantly higher rates of system use than other users (mean use=12.55 searches, S.D.=13.18 versus mean use=8.15 searches, S.D.=9.18; t=2.322, d.f.=154 P=0.022). Comparison of participants' views pre- and post- the trial, showed that post-trial clinicians expressed more positive views about searching for information during a consultation (chi(2)=27.40, d.f.=4, P< or =0.001) and a significantly greater number reported seeking information between consultations as a result of having access to an online evidence system in their consulting rooms (chi(2)=9.818, d.f.=2, P=0.010).\n Clinicians' use of an online evidence system was directly related to their reported experiences of improvements in patient care. Post-trial clinicians positively changed their views about having time to search for information and pursued more questions during clinic hours.", "It is possible to provide patients with secure access to their medical records using the Internet. Such access may assist patients in the self-management of chronic diseases such as heart failure.\n To assess how a patient-accessible online medical record affects patient care and clinic operations. The SPPARO (System Providing Access to Records Online) software consisted of a web-based electronic medical record, an educational guide, and a messaging system enabling electronic communication between the patient and staff.\n A randomized controlled trial was conducted in a specialty practice for patients with heart failure. Surveys assessing doctor-patient communication, adherence, and health status were conducted at baseline, 6 months, and 1 year. Use of the system, message volume, utilization of clinical services, and mortality were monitored.\n One hundred and seven patients were enrolled (54 intervention and 53 controls). At 12 months, the intervention group was not found to be superior in self-efficacy (KCCQ self-efficacy score 91 vs. 85, p=0.08), but was superior in general adherence (MOS compliance score 85 vs. 78, p=0.01). A trend was observed for better satisfaction with doctor-patient communication. The intervention group had more emergency department visits (20 vs. 8, p=0.03), but these visits were not temporally related to use of the online medical record. There were no adverse effects from use of the system.\n Providing patients with congestive heart failure access to an online medical record was feasible and improved adherence. An effect on health status could not be demonstrated in this pilot study.", "Translation of evidence-based guidelines into clinical practice has been inconsistent. We performed a randomized, controlled trial of guideline-based care suggestions delivered to physicians when writing orders on computer workstations.\n Inner-city academic general internal medicine practice.\n Randomized, controlled trial of 246 physicians (25 percent faculty general internists, 75 percent internal medicine residents) and 20 outpatient pharmacists. We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease. Care suggestions concerning drugs and monitoring were delivered to a random half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations. A 2 x 2 factorial randomization of practice sessions and pharmacists resulted in four groups of patients: physician intervention, pharmacist intervention, both interventions, and controls. DATA EXTRACTION/COLLECTION METHODS: Adherence to the guidelines and clinical activity was assessed using patients' electronic medical records. Health-related quality of life, medication adherence, and satisfaction with care were assessed using telephone questionnaires.\n During their year in the study, patients made an average of five scheduled primary care visits. There were no differences between groups in adherence to the care suggestions, generic or condition-specific quality of life, satisfaction with physicians or pharmacists, medication compliance, emergency department visits, or hospitalizations. Physicians receiving the intervention had significantly higher total health care costs. Physician attitudes toward guidelines were mixed.\n Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease.", "The aim of this study was to evaluate the impact of an integrated patient-specific electronic clinical reminder system on diabetes and coronary artery disease (CAD) care and to assess physician attitudes toward this reminder system.\n We enrolled 194 primary care physicians caring for 4549 patients with diabetes and 2199 patients with CAD at 20 ambulatory clinics. Clinics were randomized so that physicians received either evidence-based electronic reminders within their patients' electronic medical record or usual care. There were five reminders for diabetes care and four reminders for CAD care.\n The primary outcome was receipt of recommended care for diabetes and CAD. We created a summary outcome to assess the odds of increased compliance with overall diabetes care (based on five measures) and overall CAD care (based on four measures). We surveyed physicians to assess attitudes toward the reminder system.\n Baseline adherence rates to all quality measures were low. While electronic reminders increased the odds of recommended diabetes care (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.01-1.67) and CAD (OR 1.25, 95% CI 1.01-1.55), the impact of individual reminders was variable. A total of three of nine reminders effectively increased rates of recommended care for diabetes or CAD. The majority of physicians (76%) thought that reminders improved quality of care.\n An integrated electronic reminder system resulted in variable improvement in care for diabetes and CAD. These improvements were often limited and quality gaps persist.", "Electronic information systems have been proposed as one means to reduce medical errors of commission (doing the wrong thing) and omission (not providing indicated care).\n To assess the effects of computer-based cardiac care suggestions.\n A randomized, controlled trial targeting primary care physicians and pharmacists.\n A total of 706 outpatients with heart failure and/or ischemic heart disease.\n Evidence-based cardiac care suggestions, approved by a panel of local cardiologists and general internists, were displayed to physicians and pharmacists as they cared for enrolled patients.\n Adherence with the care suggestions, generic and condition-specific quality of life, acute exacerbations of their cardiac disease, medication compliance, health care costs, satisfaction with care, and physicians' attitudes toward guidelines.\n Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions. The intervention had no effect on physicians' adherence to the care suggestions (23% for intervention patients vs 22% for controls). There were no intervention-control differences in quality of life, medication compliance, health care utilization, costs, or satisfaction with care. Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients.\n Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease. Future studies must weigh the benefits and costs of different (and perhaps more Draconian) methods of affecting clinician behavior.", "A double-blind randomised controlled trial was conducted on a group of Hong Kong hospital clinicians. The objective was to test if a three-hour educational workshop (with supervised hands-on practice) is more effective (than no training) to improve clinical question formulation, information-seeking skills, knowledge, attitudes, and search outcomes. The design was a post-test-only control group; recruitment by stratified randomization (by profession), blocked at 800. End-user training was more effective than no training in improving clinical question formulation, in raising awareness, knowledge, confidence and use of databases, but had made no impact on preference for secondary databases. It changed the attitude of clinicians to become more positive towards the use of electronic information services (EIS). Participants had higher search performance and outcomes (satisfaction with information obtained (NNT = 3), EIS satisfaction (NNT = 3) and success in problem solving (NNT = 4)). The workshop improved knowledge and skills in evidence-based searching, but this effect gradually eroded with time. Search logs confirmed that follow-up is required if effects are to be sustained. Longer effects on search behaviours appear to be positive. A randomised controlled trial is valuable in identifying cause-and-effect relations and to quantify the magnitude of the effects for management decision-making.", "To assess the effects on information exchange of electronic communication between physicians co-treating diabetic patients.\n Comparison of traditional paper-based communication for reporting and electronic communication.\n General practitioners and an internal medicine outpatient clinic of an urban public hospital.\n A total of 275 diabetic patients, and the 32 general practitioners and one internal medicine consultant who cared for them. Intervention: An electronic communication network, linking up the computer-based patient records of the physicians, thus enabling electronic data interchange.\n Number of letters sent and received per year by the general practitioners, the number of diabetes-related parameters (e.g. results of laboratory tests) in the patient records, and HBA1C levels.\n Intervention GPs received more messages per year (1.6 per patient) than control GPs (0.5 per patient, P<0.05). Significant higher availability (P<0.05) was achieved for data on HBA1C levels, fructosamine levels, blood pressure measurements, cholesterol levels, triglyceride levels and weight measurements. Intervention patients showed a slight but significant decrease of HBA1C levels in the second semester of 1994 (from 7.0 to 6.8, P = 0.03), control patients also showed a slightly decreased group mean, but this change was not significant (from 6.6 to 6.5, P = 0.52). The magnitudes of these mean differences, however, were not significantly different (intervention group: 0.21; control group: 0.12, P = 0.68).\n The electronic communication network for exchanging consultation outcomes significantly increased frequency of communication and the availability of data to the general practitioner on diagnostic procedures performed in the hospital, thus providing more complete information about the care that patients are receiving. A large-scale experiment over a longer period of time is needed to assess the effects of improved communication on quality of care.", "The study aimed to improve continuity of care for patients undergoing major gynaecological surgery, by increasing their general practitioners' contact with the hospital and providing a comprehensive discharge summary.\n Prospective randomised study of 200 patients admitted to a gynaecological oncology ward, and their GPs. Visits and telephone calls by GPs to hospital during their patients' admission were measured, with and without invitation and offer of payment for contact. A discharge summary was distributed. Postdischarge questionnaires surveyed patient satisfaction with care, confidence in future management by the GPs, and GP confidence in continuing patient care.\n Significant increases in contact rates by the GPs followed invitation. The discharge summary was not effectively distributed. No significant differences in patient satisfaction and confidence in future management by their GPs were found. General practitioners valued hospital contact most in meeting their patients' needs for information.\n Personal invitation increases GP contact with hospitals. While no statistically significant improvements in patient satisfaction or GP confidence were shown, the data suggested that GPs value contact to meet patient information needs.", "We tested whether off-line data analysis, instead of event monitoring, was a viable method for initiating a clinical quality alert. A cohort of patients eligible for an alert was identified by off-line data analysis and a flag was set in their ambulatory Electronic Medical Records. One hundred clinicians were randomly assigned either to a control group or to a group that received the alert when viewing the electronic medical record of eligible patients. Primarily due to actions of their clinicians, 315 of the 580 patients (54.3%) seen by alerted clinicians were no longer eligible for the alert at the end of the one month study, compared to 128 of the 496 patients (25.8%) seen by control clinicians (p<.001). When not alerted, Allied Health clinicians were less likely than physicians to prescribe aspirin, but they responded similarly to the alert. There were no differences in response by specialty or gender of the clinician. Off-line data analysis proved to be an effective method of initiating a clinical alert." ]

[ "1396198", "6350957", "1411848", "1098732", "343312", "7018164", "2606014", "769913", "9166304" ]

[ "Treatment of symptomatic trichomoniasis among adult women using oral nitroimidazoles.", "Single oral dose of ornidazole in women with vaginal trichomoniasis.", "Split-dose metronidazole or single-dose tinidazole for the treatment of vaginal trichomoniasis.", "Treatment of trichomoniasis in the female. A comparison of metronidazole and nimorazole.", "Treatment of intestinal amoebiasis and vaginal trichomoniasis with panidazole and its comparison with metronidazole.", "A double-blind study of the value of treatment with a single dose tinidazole of partners to females with trichomoniasis.", "Comparison of four nitroimidazole compounds for treatment of symptomatic amoebiasis in Kenya.", "Two-day treatment of trichomoniasis in the female. Comparison of metronidazole and nimorazole.", "The minimum single oral metronidazole dose for treating trichomoniasis: a randomized, blinded study." ]

[ "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.", "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.", "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.", "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.", "A dose range study in 18 patients suffering from intestinal amoebiasis and treated with doses of panidazole between 1.0 and 2.0 g per day for six days revealed that the best therapeutic results were obtained with the higher dose. This dose was then compared with metronidazole, at the same dose, in a clinical trial in 100 patients with intestinal amoebiasis. Cure rates were 68% and 80% for the two drugs respectively. In 100 cases of vaginal trichomoniasis treated with panidazole at the dose of 1.0 g per day for seven days in half of the patients and for 10 days in the other half, we obtained 50% and 60% cure rates. The results of our studies with both amoebiasis and trichomoniasis were not superior to those obtained with metronidazole and other nitroimidazole derivatives. Side effects were found in 74% of the patients treated for amoebiasis and in 46% of the cases treated for trichomoniasis. No toxic effects were revealed by haematological, biochemical and renal function tests nor by cardiovascular studies.", "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.", "Four antiamoebic drugs currently used in many Kenyan hospitals and health centres were compared for their efficacy on symptomatic luminal amoebiasis in Kiambu, Kilifi, and Machakos hospitals during this study. The drugs were; the brand metronidazole (Flagyl, May & Baker, Kenya Ltd.), the generic metronidazole (Metrozol, Cosmos Ltd., Nairobi, Kenya), the brand tinidazole (Fasigyn, Pfizer Laboratories Ltd.) and the generic tinidazole (Tynazole Laboratory and Allied Equipments, Kenya Ltd). Clinical cure was achieved in all individuals receiving any of the four drugs. Parasitological cure was better for those receiving either Flagyl or Fasigyn, than those receiving the generic counterparts. Both parasitological and clinical cures were achieved in about 50% of all those who received either Flagyl or Fasigyn. It appears that Flagyl and Fasigyn are not as efficacious as previously reported but are still much better than their generic counterparts for the treatment of symptomatic Entamoeba histolytica infections.", "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.", "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." ]

[ "1350338", "6227304", "769630", "17689192", "1532760", "10208073", "12825916", "15726029", "17459741" ]

[ "Hypnosis or cognitive behavioral training for the reduction of pain and nausea during cancer treatment: a controlled clinical trial.", "Hypnosis compared to relaxation in the outpatient management of chronic low back pain.", "Acupuncture for chronic shoulder pain. An experimental study with attention to the role of placebo and hypnotic susceptibility.", "Hypnosis in the management of persistent idiopathic orofacial pain--clinical and psychosocial findings.", "Randomised clinical trial of manipulative therapy and physiotherapy for persistent back and neck complaints: results of one year follow up.", "Clinical hypnosis versus cognitive behavioral training for pain management with pediatric cancer patients undergoing bone marrow aspirations.", "Clinical hypnosis in the alleviation of procedure-related pain in pediatric oncology patients.", "Long-term follow-up of a randomized clinical trial assessing the efficacy of medication, acupuncture, and spinal manipulation for chronic mechanical spinal pain syndromes.", "A randomised controlled study of reflexology for the management of chronic low back pain." ]

[ "Few controlled clinical trials have tested the efficacy of psychological techniques for reducing cancer pain or post-chemotherapy nausea and emesis. In this study, 67 bone marrow transplant patients with hematological malignancies were randomly assigned to one of four groups prior to beginning transplantation conditioning: (1) hypnosis training (HYP); (2) cognitive behavioral coping skills training (CB); (3) therapist contact control (TC); or (4) treatment as usual (TAU; no treatment control). Patients completed measures of physical functioning (Sickness Impact Profile; SIP) and psychological functioning (Brief Symptom Inventory; BSI), which were used as covariates in the analyses. Biodemographic variables included gender, age and a risk variable based on diagnosis and number of remissions or relapses. Patients in the HYP, CB and TC groups met with a clinical psychologist for two pre-transplant training sessions and ten in-hospital \"booster\" sessions during the course of transplantation. Forty-five patients completed the study and provided all covariate data, and 80% of the time series outcome data. Analyses of the principal study variables indicated that hypnosis was effective in reducing reported oral pain for patients undergoing marrow transplantation. Risk, SIP, and BSI pre-transplant were found to be effective predictors of inpatient physical symptoms. Nausea, emesis and opioid use did not differ significantly between the treatment groups. The cognitive behavioral intervention, as applied in this study, was not effective in reducing the symptoms measured.", "Chronic low back pain (CLBP) presents a problem of massive dimensions. While inpatient approaches have been evaluated, outpatient treatment programs have received relatively little examination. Hypnosis and relaxation are two powerful techniques amenable to outpatient use. Seventeen outpatient subjects suffering from CLBP were assigned to either Self-Hypnosis (n = 9) or Relaxation (n = 8) treatments. Following pretreatment assessment, all subjects attended a single placebo session in which they received minimal EMG feedback. One week later the subjects began eight individual weekly treatment sessions. Subjects were assessed on a number of dependent variables at pretreatment, following the placebo phase, one week after the completion of treatment, and three months after treatment ended. Subjects in both groups showed significant decrements in such measures as average pain rating, pain as measured by derivations from the McGill Pain Questionnaire, level of depression, and length of pain analog line. Self-Hypnosis subjects reported less time to sleep onset, and physicians rated their use of medication as less problematic after treatment. While both treatments were effective, neither proved superior to the other. The placebo treatment produced nonsignificant improvement.", "One half of 42 subjects treated for painful shoulders received classic acupuncture, and one half received a placebo in which the needles did not penetrate the skin. Half of each of these groups was treated in a positive setting to encourage the subject, and half in a negative setting designed to keep encouragement at a minimum. All patients were independently rated for susceptibility to hypnosis. Although range of motion did not improve, the majority of patients reported significant improvement in shoulder discomfort to a blind evaluator after treatment; placebo and acupuncture groups did not differ in this respect, however. The positive and negative settings did not affect treatment outcome. In all groups, those who were not rated as highly susceptible to hypnosis tended to fail to achieve the highest levels of relief, but such differences were not statistically significant.", "This controlled and patient blinded study tested the effect of hypnosis on persistent idiopathic orofacial pain (PIOP) in terms of clinical and psychosocial findings. Forty-one PIOP were randomized to active hypnotic intervention or simple relaxation as control for five individual 1-h sessions. Primary outcome was average pain intensity scored three times daily in a pain diary using visual analogue scale (VAS). Secondary outcome measures were pain quality assessed by McGill pain questionnaire (MPQ), psychological symptoms assessed by symptom check list (SCL), quality of life assessed by SF36, sleep quality, and consumption of analgesic. Data were compared between groups before and after treatment using ANOVA models and paired t-tests. The change in VAS pain scores from baseline to the last treatment (t4) was (33.1+/-7.4%) in the hypnosis group and (3.2+/-5.4%) in the control group (P<0.03). In the hypnosis group, highly hypnotic susceptible patients had greater decreases in VAS pain scores (55.0+/-12.3%) when compared to less susceptible patients (17.9+/-6.7%) (P<0.02). After the last treatment there were also statistically significant differences between groups in perceived pain area (MPQ) and the use of weak analgesics (P<0.03). There were no statistically significant changes in SCL or SF36 scores from baseline to t4. In conclusion, hypnosis seems to offer clinically relevant pain relief in PIOP, particularly in highly susceptible patients. However, stress coping skills and unresolved psychological problems need to be included in a comprehensive management plan in order also to address psychological symptoms and quality of life.", "To compare the effectiveness of manipulative therapy, physiotherapy, treatment by the general practitioner, and placebo therapy in patients with persistent non-specific back and neck complaints.\n Randomised clinical trial.\n Primary health care in the Netherlands.\n 256 patients with non-specific back and neck complaints of at least six weeks' duration who had not received physiotherapy or manipulative therapy in the past two years.\n At the discretion of the manipulative therapists, physiotherapists, and general practitioners. Physiotherapy consisted of exercises, massage, and physical therapy (heat, electrotherapy, ultrasound, shortwave diathermy). Manipulative therapy consisted of manipulation and mobilisation of the spine. Treatment by general practitioners consisted of drugs (for example, analgesics), advice about posture, home exercises, and (bed)rest. Placebo treatment consisted of detuned shortwave diathermy (10 minutes) and detuned ultrasound (10 minutes).\n Changes in severity of the main complaint and limitation of physical functioning measured on 10 point scales by a blinded research assistant and global perceived effect measured on a 6 point scale by the patients.\n Many patients in the general practitioner and placebo groups received other treatment during follow up. Improvement in the main complaint was larger with manipulative therapy (4.5) than with physiotherapy (3.8) after 12 months' follow up (difference 0.9; 95% confidence interval 0.1 to 1.7). Manipulative therapy also gave larger improvements in physical functioning (difference 0.6; -0.1 to 1.3). The global perceived effect after six and 12 months' follow up was similar for both treatments.\n Manipulative therapy and physiotherapy are better than general practitioner and placebo treatment. Furthermore, manipulative therapy is slightly better than physiotherapy after 12 months.", "A randomized controlled trial was conducted to compare the efficacy of clinical hypnosis versus cognitive behavioral (CB) coping skills training in alleviating the pain and distress of 30 pediatric cancer patients (age 5 to 15 years) undergoing bone marrow aspirations. Patients were randomized to one of three groups: hypnosis, a package of CB coping skills, and no intervention. Patients who received either hypnosis or CB reported less pain and pain-related anxiety than did control patients and less pain and anxiety than at their own baseline. Hypnosis and CB were similarly effective in the relief of pain. Results also indicated that children reported more anxiety and exhibited more behavioral distress in the CB group than in the hypnosis group. It is concluded that hypnosis and CB coping skills are effective in preparing pediatric oncology patients for bone marrow aspiration.", "This prospective controlled trial investigated the efficacy of a manual-based clinical hypnosis intervention in alleviating pain in 80 pediatric cancer patients (6-16 years of age) undergoing regular lumbar punctures. Patients were randomly assigned to 1 of 4 groups: direct hypnosis with standard medical treatment, indirect hypnosis with standard medical treatment, attention control with standard medical treatment, and standard medical treatment alone. Patients in the hypnosis groups reported less pain and anxiety and were rated as demonstrating less behavioral distress than those in the control groups. Direct and indirect suggestions were equally effective, and the level of hypnotizability was significantly associated with treatment benefit in the hypnosis groups. Therapeutic benefit degraded when patients were switched to self-hypnosis. The study indicates that hypnosis is effective in preparing pediatric oncology patients for lumbar puncture, but the presence of the therapist may be critical.", "To assess the long-term benefits of medication, needle acupuncture, and spinal manipulation as exclusive and standardized treatment regimens in patients with chronic (>13 weeks) spinal pain syndromes.\n Extended follow-up (>1 year) of a randomized clinical trial was conducted at the multidisciplinary spinal pain unit of Townsville's General Hospital between February 1999 and October 2001.\n Of the 115 patients originally randomized, 69 had exclusively been treated with the randomly allocated treatment during the 9-week treatment period (results at 9 weeks were reported earlier). These patients were followed up and assessed again 1 year after inception into the study reapplying the same instruments (ie, Oswestry Back Pain Index, Neck Disability Index, Short-Form-36, and Visual Analogue Scales). Questionnaires were obtained from 62 patients reflecting a retention proportion of 90%. The main analysis was restricted to 40 patients who had received exclusively the randomly allocated treatment for the whole observation period since randomization.\n Comparisons of initial and extended follow-up questionnaires to assess absolute efficacy showed that only the application of spinal manipulation revealed broad-based long-term benefit: 5 of the 7 main outcome measures showed significant improvements compared with only 1 item in each of the acupuncture and the medication groups.\n In patients with chronic spinal pain syndromes, spinal manipulation, if not contraindicated, may be the only treatment modality of the assessed regimens that provides broad and significant long-term benefit.", "The use of complementary and alternative medicine (CAM) for the management of chronic low back pain (CLBP) continues to rise. However, questions regarding the efficacy of many CAM therapies for CLBP remain unresolved. The present study investigated the effectiveness of reflexology for CLBP. A pragmatic randomised controlled trial was conducted. N=243 patients were randomised to one of three groups: reflexology, relaxation, or non-intervention (usual care). All completed a questionnaire booklet before and after the treatment phase, and at six months follow up. This measured their general health status, pain, functioning, coping strategies and mood. After adjusting for pre-treatment scores repeated measures ANCOVA found no significant differences between the groups pre and post treatment on the primary outcome measures of pain and functioning. There was a main effect of pain reduction, irrespective of group. Trends in the data illustrated the pain reduction was greatest in the reflexology group. Thus, the current study does not indicate that adding reflexology to usual GP care for the management of CLBP is any more effective than usual GP care alone." ]

[ "2681348", "11994337", "8359791", "7634503", "8998124", "12193430", "9734940", "14670773", "12014516" ]

[ "Acceleration of growth in Turner syndrome patients treated with growth hormone: summary of three-year results.", "Growth hormone and low dose estrogen in Turner syndrome: results of a United States multi-center trial to near-final height.", "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.", "The growth and cardiovascular effects of high dose growth hormone therapy in idiopathic short stature.", "Low-dose recombinant human growth hormone increases body weight and lean body mass in patients with short bowel syndrome.", "High dose growth hormone treatment induces acceleration of skeletal maturation and an earlier onset of puberty in children with idiopathic short stature.", "Randomised trial of growth hormone in short normal girls.", "Prospective randomised treatment with recombinant human growth hormone in cystic fibrosis.", "Recombinant human growth hormone treatment, using two dose regimens in children with chronic renal failure--a report on linear growth and adverse effects." ]

[ "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.", "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.", "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.", "It is possible that high dose GH treatment may have beneficial effects on growth but important adverse effects on cardiac function. We have therefore investigated the efficacy and cardiovascular effects of high dose biosynthetic human GH (r-hGH) treatment in children with idiopathic short stature and a normal pretreatment height velocity.\n Randomized controlled study.\n Twenty-nine short (height SDS < 1.5), normally growing (height velocity SDS > -1.5), prepubertal children referred to two specialist growth clinics.\n Children were randomly assigned to an observation group or to receive 'standard' (20 IU/m2/week) or 'high' (40 IU/m2/week) dose r-hGH by daily subcutaneous injection. At the end of 1 year the observation group were randomly assigned to 'standard' or 'high' dose r-hGH therapy for the second year of the study. Regular growth, biochemical and echocardiographic monitoring were performed throughout the study period.\n Changes in height velocity, HtSDS for bone age (HtSDSBA), left ventricular mass index (LVMI) and left ventricular function (fractional shortening) during 2 years treatment.\n Twenty-seven children completed the study. Ht velocity SDS increased with r-hGH therapy in a dose dependent fashion. First-year height velocity SDS was +5.7 in the high dose r-hGH group compared with +2.7 in the standard dose r-hGH group and -0.5 in the observation group (P < 0.001). In those children treated for 2 years HtSDSBA was -0.5 in the high dose group but had not changed significantly in the standard dose group (-1.7) (P = 0.01). After one year r-hGH treatment LVMI was 71 g/m2 (observation group), 73 g/m2 (20 IU/m2/week group) and 74 g/m2 (40 IU/m2/week group) (P = 0.77). LVMI increased significantly from baseline to 76 g/m2 after 2 years therapy with 40 IU/m2/week r-hGH (P = 0.04) but nevertheless remained within the normal range. Fractional shortening did not change significantly over 2 years of r-hGH therapy.\n High dose (40 IU/m2/week) r-hGH treatment of children with idiopathic short stature resulted in a greater short-term acceleration in growth rate than 'standard' dose therapy without an excessive advance in skeletal maturity and probably represents the optimal growth promoting dose for short, normally growing children. Whether continued high dose r-hGH therapy increases final height requires further study. Left ventricular morphology and function remained within the normal range during r-hGH therapy but regular monitoring of cardiovascular status should continue in non-GHD children receiving r-hGH in high doses over a longer time period.", "The authors investigate the effects of low dose recombinant human growth hormone (rhGH) on body composition and absorptive capacity in patients with short bowel syndrome from Crohn's disease.\n Patients with short bowel syndrome usually are malnourished because of malabsorption. The anabolic effects of high doses of rhGH have been tested in different clinical catabolic conditions, recently including patients with short bowel syndrome. The authors have investigated the effects of low-dose rhGH in short bowel syndrome in a placebo-controlled crossover clinical trial.\n Ten patients were treated with daily subcutaneous doses of rhGH/placebo (0.5 international units/kg-1 per week-1 = 0.024 mg/kg-1 per day-1) for 8 weeks in a randomized, double-blind, placebo-controlled crossover clinical trial with a minimum of 12 weeks wash-out. Absorptive capacity and biochemical parameters were investigated in a metabolic ward before treatment and during first and last week of treatment. Body composition was determined by DEXA-Scan (Lunar DPX, Scanexport Medical, Helsingborg, Sweden), impedance analysis, and whole body potassium counting.\n Low-dose rhGH doubled serum levels of insulin-like growth factor-1 (IGF-1) and increased body weight, lean body mass, and total body potassium by 5% (p < 0.05). Fat-free mass and total body water increased by 6% (p = 0.008). Increases in IGF-1 levels correlated with increases in fat-free mass (r = 0.77, p < 0.02). No significant changes in absorptive capacity of water, energy, or protein were detected.\n Eight weeks of low-dose rhGH treatment leads to increases in body weight, lean body mass, and fat-free mass in patients with short bowel syndrome, correlated to increases in IGF-1 levels.", "Long term growth hormone (GH) treatment in children with idiopathic short stature (ISS) results in a relatively small mean gain in final height of 3-9 cm, which may not justify the cost of treatment. As it is unknown whether GH treatment during puberty adds to final height gain, we sought to improve the cost-benefit ratio, employing a study design with high dose GH treatment restricted to the prepubertal period.\n To assess the effect of short term, high dose GH treatment before puberty on growth, bone maturation, and pubertal onset.\n Five year results of a randomised controlled study are reported. Twenty six boys and nine girls were randomly assigned to a GH treatment group (n = 17) or a control group (n = 18). Inclusion criteria were: no signs of puberty, height less than -2 SDS, age 4-8 years for girls or 4-10 years for boys, GH concentration >10 micro g/l after provocation, and normal body proportions. To assess GH responsiveness, children assigned to the GH treatment group received GH treatment for two periods of three months (1.5 IU/m2/day and 3.0 IU/m2/day), separated by three month washout periods, during the first year of study. High dose GH treatment (6.0 IU/m2/day) was then started and continued for at least two full years. When puberty occurred, GH treatment was discontinued at the end of a complete year's treatment (for example, three or four years of GH treatment).\n In response to at least two years on high dose GH treatment, mean (SD) height SDS for chronological age increased significantly in GH treated children from -2.6 (0.5) to -1.3 (0.5) after two years and -1.4 (0.5) SDS after five years of study. No changes in height SDS were observed in controls. A rapid rate of bone maturation of 3.6 years/2 years in treated children compared to 2 years/2 years in controls was observed in response to two years high dose GH treatment. Height SDS for bone age was not significantly different between groups during the study period. GH treated children entered into puberty at a significantly earlier age compared to controls.\n High dose GH treatment before puberty accelerates bone age and induces an earlier onset of puberty. This may limit the potential therapeutic benefit of this regimen in ISS.", "There are few data on the long-term outcome of growth-hormone treatment in short normal children. We assessed the impact of growth-hormone treatment on pubertal development and near-final height in girls.\n In a randomised controlled trial, we studied ten girls, with a mean age of 8.07 years and height 2 SDs or more below the mean for their age, and eight short untreated controls matched for age, and 20 short untreated girls who did not give consent for randomisation. The girls received either 30 IU/m2 somatropin per week as daily subcutaneous injections or no treatment. We assessed pubertal staging and height gain every 6 months.\n Eight treated girls completed a mean of 6.2 years' therapy. By a mean age of 16.4 years, their mean height SD score had changed significantly from -2.42 to -1.14 (p=0.008) and they were, on average, 7.5 cm taller than the girls in the control group (height SD scores did not change significantly from -2.55) and 6.0 cm taller than the non-consent group. The timing of each pubertal stage, and the age and amplitude of peak height velocity were similar for all groups.\n Growth-hormone therapy effectively increased height SD score among short normal girls started on treatment in early to mid childhood, with no untoward effect on pubertal progression.", "To evaluate the efficacy and safety of treatment with recombinant growth hormone (rGH) in patients with cystic fibrosis (CF).\n Twenty patients with CF (aged 10-23 years) were randomised to age and sex matched treatment and control groups. The treatment group received daily subcutaneous injections of 1 IU/kg/wk rGH for 12 months. Pulmonary function (forced expiratory volume in one second (FEV1) and airway resistance), exercise capacity measured with a bicycle ergometer, body composition (dual energy x ray absorptiometry), and weight were assessed at the beginning of the study and after 6 and 12 months.\n rGH treatment did not improve weight and pulmonary function, but lean body mass increased significantly in the treatment group. Exercise capacity increased in the treatment group from 143 (16) W (mean (SD)) to 164 (19) W after 12 months of rGH treatment.\n Treatment of CF patients with rGH for one year improved the exercise capacity significantly but not pulmonary function. The improved exercise capacity needs confirmation in a larger population before such an expensive treatment is justified.", "The aim of this study was to study the efficiency and the adverse effects of 2 or 4 IU/m2/day of growth hormone (GH) in the first year and 4 IU/m2/day in the second. Of 29 growth-retarded children with chronic renal failure (CRF) (aged 3.4-15.1 years), 23 completed the first year of therapy, and 16 completed the second year. Height velocity SDS (HVSDS) increased in the first year in the low-dose group with 3.0, and 3.8 in the high-dose group. In the second year, HVSDS increased by 1.3 in the low-dose group and by 2.1 in high-dose group (p < 0.05). The IGF-I/IGFBP-3 ratio rose identically during the first year (p < 0.01). The retarded bone age did not advance inappropriately. The integrated insulin levels (AUC) increased significantly after 1 year of therapy in both groups. HbA1c, levels did not change. The number of adverse events was highest in the low-dose group, in which one patient developed overt insulin dependent diabetes mellitus. In conclusion, glucose metabolism should be monitored in children with CRF during rhGH-treatment. GH therapy in our patients resulted in a significant increase in height velocity with no inappropriate bone age progression and few serious adverse effects, all without relation to the dose of rhGH. The low start dose (2 IU/m2/ day) was of no advantage compared to the high dose." ]

[ "16616557", "3755517", "16641396", "12819167", "15956998", "11737959", "15695996", "21596735", "2911997" ]

[ "Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial.", "Vitamin D supplementation in pregnancy: a controlled trial of two methods.", "Vitamins C and E and the risks of preeclampsia and perinatal complications.", "Effects of vitamin E supplementation during erythropoietin treatment of the anaemia of prematurity.", "Effect of vitamin supplementation to HIV-infected pregnant women on the micronutrient status of their infants.", "Vitamin A and iron supplementation of Indonesian pregnant women benefits vitamin A status of their infants.", "Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial.", "Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial.", "Vitamin E supplementation in very-low-birth-weight infants: long-term follow-up at two different levels of vitamin E supplementation." ]

[ "Oxidative stress could play a part in pre-eclampsia, and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder. Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors.\n We did a randomised, placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals. We assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol; n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy until delivery. Our primary endpoint was pre-eclampsia, and our main secondary endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th customised birthweight centile). Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 62368611 .\n Of 2404 patients treated, we analysed 2395 (99.6%). The incidence of pre-eclampsia was similar in treatment placebo groups (15% [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies were born to women who took antioxidants than to controls (28% [n=387] vs 24% [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31]).\n Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight. As such, use of these high-dose antioxidants is not justified in pregnancy.", "A randomized study was conducted to evaluate the effects of single-dose and daily vitamin D supplementation in pregnant women during the last trimester of a winter pregnancy in the Northwest of France. The women were divided into three randomized groups: one (N = 21) was given a vitamin D2 supplement of 1000 IU/day during the last three months of pregnancy, one (N = 27) was given a single oral dose of 5 mg at the seventh month of pregnancy, and one (N = 29) acted as a control. Venous plasma samples were obtained at delivery from the women and from cord blood, and levels of calcium, 25-OHD, and 1,25(OH)2D were determined. No significant difference in plasma calcium concentration was found among the three groups, but within each group plasma calcium concentrations were higher in the cord samples than in the respective maternal samples. The levels of the two metabolites measured were consistently lower in the cord samples than in the respective maternal samples. Cord 25-OHD concentrations correlated with those of maternal plasma. No significant modification of maternal calciuria or of the birth weight of term infants was observed. 25-OHD concentrations were greater in maternal and cord plasma from treated mothers, but only a slight difference was observed between the supplemented groups. 1,25(OH)2D concentrations were not significantly different in the three groups. A single 5-mg dose of vitamin D given orally at the seventh month of pregnancy provides effective prophylaxis in the authors' region.", "Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain.\n We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age.\n Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16).\n Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).\n Copyright 2006 Massachusetts Medical Society.", "To evaluate the effects of vitamin E supplementation on haemoglobin concentration and the requirement for transfusion in premature infants treated with erythropoietin and iron.\n Randomised, double blind, placebo controlled trial. Thirty infants </=32 weeks gestation and </=1250 g birth weight, who were defined as stable based on minimal requirements for respiratory support and phlebotomy, and absence of major congenital anomalies were enrolled. All were treated with erythropoietin and iron, and were randomised to receive, in addition, either vitamin E 50 IU/day or placebo for eight weeks or until discharge, whichever came first.\n Despite higher vitamin E (alpha-tocopherol) levels in the experimental group in weeks 3 (49.0 v 28.1 micro mol/l) and 8 (66.2 v 38.5 micro mol/l), there were no differences in haemoglobin, reticulocyte count, iron concentration, or transfusion requirement.\n Oral vitamin E supplementation at 50 IU/day does not increase the response of preterm infants to erythropoietin and iron. Vitamin E obtained through standard nutrition may have been sufficient or higher doses may be required.", "We examined whether supplementation with vitamin A and/or vitamins B, C, and E to HIV-infected women during pregnancy and lactation is related to increased concentrations of vitamins A, B12, and E in their infants during the first 6 months of life.\n We carried out a randomized clinical trial among 716 mother-infant pairs in Dar-es-Salaam, Tanzania. Women were randomly allocated to receive a daily oral dose of one of four regimens: vitamin A, multivitamins (B, C, and E), multivitamins including A, or placebo. Supplementation started at first prenatal visit and continued after delivery throughout the breastfeeding period. The serum concentration of vitamins A, E and B12 was measured in infants at 6 weeks and 6 months postpartum.\n Maternal vitamin A supplementation increased serum retinol in the infants at 6 weeks (mean difference=0.09 micromol/l, P<0.0001) and 6 months (mean difference=0.06 micromol/l, P=0.0002), and decreased the prevalence of vitamin A deficiency, but had no impact on serum vitamins E or B12. Multivitamins increased serum vitamin B12 at 6 weeks and 6 months (mean differences=176 pmol/l, P<0.0001 and 127 pmol/l, P<0.0001, respectively) and vitamin E (mean differences=1.8 micromol/l, P=0.0008 and 1.1 micromol/l, P=0.004, respectively) and decreased the prevalence of vitamin B12 deficiency.\n Vitamin supplementation to HIV-1-infected women is effective in improving the vitamin status of infants during the first 6 months of age.", "Many Indonesian infants have an inadequate nutritional status, which may be due in part to inadequate maternal nutrition during pregnancy. This study was designed to investigate whether infant nutritional status could be improved by maternal vitamin A and Fe supplementation during gestation. Mothers of these infants from five villages had been randomly assigned on an individual basis, supervised and double-blind, to receive supplementation once weekly from approximately 18 weeks of pregnancy until delivery. Supplementation comprised 120 mg Fe and 500 microg folic acid with or without 4800 retinol equivalent vitamin A. Mothers of infants from four other villages who participated in the national Fe and folic acid supplementation programme were also recruited; intake of tablets was not supervised. Anthropometric and biochemical parameters of infants and their mothers were assessed approximately 4 months after delivery. Infants of mothers supplemented with vitamin A plus Fe had higher serum retinol concentrations than infants of mothers supplemented with Fe alone. However, the proportion of infants with serum retinol concentrations <0.70 micromol/l was >70 % in all groups. Maternal and infant serum retinol concentrations were correlated. Fe status, weight and length of infants were similar in all groups. Fe status of girls was better than that of boys, but boys were heavier and longer. We conclude that supplementation with vitamin A in conjunction with Fe supplementation of women during pregnancy benefits vitamin A status of their infants. However, considering the large proportion of infants with marginal serum retinol concentrations, it may still be necessary to increase their vitamin A intake.", "We sought to determine the effect of supplemental antioxidant vitamins C and E on the rate of preeclampsia in high-risk pregnant women.\n Women at risk for preeclampsia (previous preeclampsia, chronic hypertension, pregestational diabetes, or multifetal gestation) were recruited at 14 to 20 weeks' gestation and randomly assigned to receive either 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily in addition to their regular prenatal vitamins. The primary outcome was the occurrence of preeclampsia. An estimated sample size of 220 women in each arm was determined to be necessary to demonstrate a 50% reduction in the rate of preeclampsia.\n Funding was terminated after 109 women had been recruited; 9 were lost to follow-up or withdrew. We analyzed data from the remaining 100 women to look for differences in outcome and to estimate the required sample size for future studies. The rate of preeclampsia was not different: 17.3% in women who received supplemental vitamins C and E, versus 18.8% in the placebo group. Assuming a baseline rate of preeclampsia in the placebo group between 15% and 20%, we can estimate that 500 to 950 women in each arm will be required to show a clinically important reduction in the rate of preeclampsia.\n The potential benefit of vitamin C and E supplementation to prevent preeclampsia in women with clinical risk factors is smaller than we estimated. Future studies of antioxidant vitamin supplementation in this population will require more than 500 women in each arm.", "To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk.\n Randomised, blinded, placebo controlled clinical trial.\n Tertiary public hospital in Mexico City.\n Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery.\n Supplementation with a medical food-bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo-during pregnancy.\n Development of pre-eclampsia/eclampsia.\n 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ(2) = 19.41; P < 0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ(2) = 3.76; P = 0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P = 0.004; absolute risk reduction 0.09, 0.05 to 0.14).\n Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846.", "This study evaluates the need of vitamin E supplementation in very-low-birth-weight infants by long-term follow-up of plasma vitamin E status during the first 15 mo of life, with two different levels of supplementation. The subjects were 51 newborn infants with birth weights less than or equal to 1520 g. During hospitalization the infants were fed human milk. On the third day of life oral vitamin E supplementation of less than or equal to 10 mg/d was started in all infants. In addition, 23 infants selected at random were given intramuscular vitamin E (20 mg/kg/d) during the first 3 d. The data indicate that the 10 mg/d supplement resulted in an adequate plasma concentration of vitamin E. After cessation of supplementation at age 3 mo, the risk of low plasma vitamin E levels increased. Although intramuscular administration resulted in long-lasting increments in mean plasma vitamin E values, some later levels in these infants were marginal." ]

[ "17846102", "11074227", "11087767", "9169246", "12633121", "16968574", "15178953", "10982198", "18311826" ]

[ "A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia.", "Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline.", "Treatment of agitation in AD: a randomized, placebo-controlled clinical trial.", "A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia.", "A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia.", "A comparative, randomized, double-blind study of trazodone prolonged-release and sertraline in the treatment of major depressive disorder.", "Frontotemporal dementia: a randomised, controlled trial with trazodone.", "A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients.", "Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study." ]

[ "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.", "Previous comparative studies of the selective serotonin reuptake inhibitors (SSRIs) have rarely included a placebo control group and have rarely demonstrated significant between-group differences. The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs, citalopram and sertraline.\n Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were randomized to 24 weeks of double-blind treatment with citalopram (20-60 mg/day), sertraline (50-150 mg/day), or a placebo. The primary efficacy measure was the Hamilton Depression Rating Scale (HAMD) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group.\n Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD, the Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impression Scale. Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group; however, sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation, and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments. The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram, but not sertraline, relative to placebo.\n This study confirms the antidepressant efficacy of two SSRIs, citalopram and sertraline. It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy.", "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.", "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.", "This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia.\n Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer's type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGI-C) scales.\n A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean +/- SE dose of risperidone was 0.95 +/- 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p <.001). A similar improvement was also seen for the CMAI total non-aggression subscale (p <.002) and for the BEHAVE-AD total (p <.001) and psychotic symptoms subscale (p =.004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p <.001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups.\n Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia.", "To evaluate the efficacy and safety of trazodone prolonged-release compared with sertraline in the treatment of patients with major depression.\n A total of 122 patients aged 19-64 years were enrolled in this multicenter, double-blind, double-dummy, randomized, comparator-controlled study. Patients received 7 days of single-blind placebo treatment followed by 6 weeks of double-blind treatment with trazodone prolonged-release 150-450 mg/day (n = 62) or sertraline 50-100 mg/day (n = 60).\n Efficacy was evaluated by mean changes from baseline in the Hamilton Depression Rating scale (HAM-D), Montgomery Asberg Depression Rating Scale, Hamilton Anxiety Rating scale, and the Clinical Global Impression-Global Improvement/Severity scores; and by the rates of patients responding to treatment and considered to be in remission. Time to onset of efficacy and safety were assessed.\n Trazodone and sertraline were equally effective in reducing depressive symptoms and promoting remission, and had similar onset times. In the Intent-to-Treat population, there were no significant differences in favor of trazodone at study endpoint in all efficacy measures, while a statistically significant difference was detected in the Per-Protocol population on HAM-D and in the percentage of responders. Analysis of HAM-D factors (anxiety/somatization, cognitive disturbance, retardation, and sleep disturbance) indicated that sleep disturbances were significantly less evident for patients taking trazodone at study endpoint. Adverse drug reactions, mostly of mild intensity, were reported in 42% of trazodone-treated patients (mainly of the nervous system) and 43% of sertraline-treated patients (mainly gastrointestinal). One event was considered to be serious: a patient treated with trazodone 450 mg/day showed moderate anxiety/tremor/insomnia and was hospitalized. Treatment was discontinued; the patient made a full recovery.\n This study showed that after 6 weeks, trazodone and sertraline were not different in reducing symptoms of depression and in producing disease remission. Tolerability profiles reflected the differing pharmacological properties of these antidepressants. Trazodone may be a therapeutic option in the treatment of patients with major depression showing prevalent sleep disturbances.", "Behavioural troubles due to frontotemporal dementia (FTD) are difficult to treat. The serotonergic system is associated with frontal lobes, the degeneration of which contributes to FTD. Trazodone increases the extracellular 5-HT levels in the frontal cortex. In a randomised, double-blind, placebo-controlled cross-over study, we investigated the effect of trazodone. There was a significant decrease in the Neuropsychiatry Inventory (NPI) total score with trazodone (p = 0.028) in the 26 evaluable patients. A decrease of more than 50% in the NPI score was observed in 10 patients with trazodone. This improvement was mainly based on the improvement of 4 items of the scale (irritability, agitation, depressive symptoms and eating disorders). The Mini-Mental State Examination was not modified and trazodone was well tolerated. Results of this first placebo-controlled trial suggest that trazodone is an effective treatment for the behavioural symptoms of FTD.\n Copyright 2004 S. Karger AG, Basel", "There has been a paucity of well-designed studies comparing selective serotonin reuptake inhibitor (SSRI) medications in the treatment of depression in the elderly. This multicenter study was designed to examine the efficacy and safety of sertraline and fluoxetine in depressed elderly outpatients. A secondary objective was to examine the effects of SSRI treatment on quality of life and cognitive function.\n Two hundred thirty-six outpatients 60 years of age and older who met DSM-III-R criteria for major depressive disorder received 1 week of single-blind placebo before being randomly assigned to 12 weeks of double-blind, parallel-group treatment with flexible daily doses of either sertraline (range, 50-100 mg) or fluoxetine (range, 20-40 mg). Primary efficacy measures consisted of the 24-item Hamilton Rating Scale for Depression and Clinical Global Impressions scale ratings. Secondary outcome assessments included clinician- and patient-rated measures of depression symptoms and factors, cognitive functioning, and quality of life, as well as plasma drug concentrations, which were correlated with clinical response.\n Both drugs produced a similarly positive response on the primary efficacy measures, with 12-week responder rates of 73% for sertraline and 71% for fluoxetine. Sertraline-treated patients showed statistically greater cognitive improvement on several measures. Both drugs were safe and well tolerated.\n Data indicate that both drugs are effective antidepressants for the treatment of depressed elderly outpatients. Differences in cognitive performance effects deserve further investigation.", "Depression is one of the most common psychiatric disturbances in Parkinson's disease (PD). Recent reviews have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD. We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor (SSRI) antidepressants differ in their short-term efficacy, because the time to onset of therapeutic benefit remains an important criterion in depression. The short-term efficacy (after 14 and 30 days) of two antidepressants (desipramine, a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram, a SSRI) was assessed in a double-blind, randomized, placebo- controlled study of 48 nondemented PD patients suffering from major depression. After 14 days, desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale (MADRS) score, compared with citalopram and placebo. Both antidepressants produced significant improvements in the MADRS score after 30 days. Mild adverse events were twice as frequent in the desipramine group as in the other groups. A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI. However, desipramine's lower tolerability may outweigh its slight short-term clinical advantage.\n (c) 2008 Movement Disorder Society." ]

[ "11843764", "9189040", "21562253", "6221247", "16286541", "7998769", "12362423", "2167452", "1519607" ]

[ "Immunoglobulin treatment versus plasma exchange in patients with chronic moderate to severe myasthenia gravis.", "Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Myasthenia Gravis Clinical Study Group.", "Comparison of IVIg and PLEX in patients with myasthenia gravis.", "[Long-term effects of plasma exchange in myasthenia. Results of a randomized study].", "Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin: a randomized double-blind clinical trial.", "A plasma exchange versus immune globulin infusion trial in chronic inflammatory demyelinating polyradiculoneuropathy.", "Randomized, controlled trial of intravenous immunoglobulin in myasthenia gravis.", "Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation.", "A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. The Canadian Apheresis Study Group." ]

[ "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.", "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.", "Both IV immunoglobulin (IVIg) and plasma exchange (PLEX) are immunomodulatory treatments used to treat patients with myasthenia gravis (MG), but the choice of which treatment to administer to patients is limited due to lack of evidence from adequately powered, masked, randomized, standardized trials.\n We randomized 84 patients with moderate to severe MG defined as a Quantitative Myasthenia Gravis Score for disease severity (QMGS) of >10.5 and worsening weakness to IVIg (Gamunex®, Talecris Biotherapeutics) 1 g/kg/day for 2 consecutive days or PLEX (Caridian Spectra) 1.0 plasma volume exchanges for 5 exchanges. The patients were evaluated at day 14 after treatment for the primary efficacy parameter of change in QMGS and secondary clinical and electrophysiologic parameters and were followed for a total of 60 days.\n Both IVIg and PLEX reduced the QMGS, and IVIg was comparable to PLEX in efficacy. The dropout rate was the same for both treatment arms and both treatments were well-tolerated. The presence of acetylcholine receptor antibodies and greater baseline disease severity predicted a better response to therapy. The postintervention status revealed that the same proportion of patients improved with treatment: 69% on IVIg and 65% on PLEX. The duration of improvement was similar with both treatments.\n IVIg has comparable efficacy to PLEX in the treatment of patients with moderate to severe MG. Both treatments are well-tolerated, and the duration of effect is comparable. Either treatment may be offered to patients depending on availability of resources. Classification of evidence: This study provides Class I evidence that IVIg and PLEX have comparable efficacy and are equally tolerated in adult patients with moderate to severe MG within 2 weeks of treatment.\n Copyright © 2011 by AAN Enterprises, Inc.", "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.", "The optimal dose of intravenous immunoglobulin (IVIG) in acute exacerbation of myasthenia gravis remains unknown. Increasing the treatment duration might provide added efficacy.\n To determine the optimal dose of IVIG for treating myasthenia gravis exacerbation.\n Randomized double-blind placebo-controlled multicenter trial designed to demonstrate superiority of the 2 g/kg dose over the 1 g/kg dose of IVIG, conducted between November 13, 1996, and October 26, 2002.\n One hundred seventy-three patients aged 15 to 85 years with acute exacerbation of myasthenia gravis.\n Participants were randomly assigned to receive 1 g/kg of IVIG on day 1 and placebo on day 2 (group 1) vs 1 g/kg of IVIG on 2 consecutive days (group 2).\n Improvement in the myasthenic muscular score after 2 weeks.\n The mean improvements in the myasthenic muscular scores after 2 weeks were 15.49 points (95% confidence interval, 12.09-18.90 points) in group 1 and 19.33 points (95% confidence interval, 15.82-22.85 points) in group 2. However, the difference between the 2 groups was not significant (effect size, 3.84 [95% confidence interval, -1.03 to 8.71]; P = .12).\n This trial found no significant superiority of 2 g/kg over 1 g/kg of IVIG in the treatment of myasthenia gravis exacerbation.", "Chronic inflammatory demyelinating polyradiculoneuropathy is a paralytic syndrome, causing considerable disability and even death. In controlled clinical trials, plasma exchange prevented or ameliorated neurological deficits, but the efficacy of immune globulin infusion remains unproved. Also unknown is whether immune globulin infusion is as effective, or more effective, than plasma exchange and what dosages and frequencies are best. In this observer-blinded study, using some objective end points not subject to bias (e.g., summated compound muscle action potential), 20 patients with progressive or static polyneuropathy were randomly assigned to receive either of the two treatments for 6 weeks, followed by a washout period, and then were assigned to receive the other treatment. Plasma exchange (twice a week for 3 weeks then once a week for 3 weeks) and immune globulin infusion (0.4 gm/kg once a week for 3 weeks, then 0.2 gm/kg once a week for the next 3 weeks) were used. End points assessed before and after treatment schedules were neurological disability score; muscle weakness of the neurological disability score; summated compound muscle action potentials of ulnar, median, and peroneal nerves; summated sensory nerve action potentials of ulnar and sural nerves; and vibratory detection threshold of the great toe using CASE IV. Observers were masked as to treatment used. Of 20 patients, 13 received both treatments whereas 4 did not worsen sufficiently to receive the second treatment--1 patient left the study during and 2 after the first treatment to receive unscheduled treatment elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS)", "We initiated a randomized, double-blinded, placebo-controlled trial of intravenous immunoglobulin (IVIG) treatment in myasthenia gravis (MG). Patients received IVIG 2 gm/kg at induction and 1 gm/kg after 3 weeks vs. 5% albumin placebo. The primary efficacy measurement was the change in the quantitative MG Score (QMG) at day 42. Fifteen patients were enrolled (6 to IVIG; 9 to placebo) before the study was terminated because of insufficient IVIG inventories. At day 42, there was no significant difference in primary or secondary outcome measurements between the two groups. In a subsequent 6-week open-label study of IVIG, positive trends were observed.\n Copyright 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 549-552, 2002", "Graft-versus-host disease (GVHD) and infection are major complications of allogeneic bone marrow transplantation. Since intravenous immunoglobulin has shown benefit in several immunodeficiency and autoimmune disorders, we studied its antimicrobial and immunomodulatory role after marrow transplantation.\n In a randomized trial of 382 patients, transplant recipients given immunoglobulin (500 mg per kilogram of body weight weekly to day 90, then monthly to day 360 after transplantation) were compared with controls not given immunoglobulin. By chance, the immunoglobulin group included more patients with advanced-stage neoplasms; otherwise, the study groups were balanced for prognostic factors.\n Control patients seronegative for cytomegalovirus who received seronegative blood products remained seronegative, but seronegative patients who received immunoglobulin and screened blood had a passive transfer of cytomegalovirus antibody (median titer, 1:64). Among the 61 seronegative patients who could be evaluated, none contracted interstitial pneumonia; among the 308 seropositive patients evaluated, 22 percent of control patients and 13 percent of immunoglobulin recipients had this complication (P = 0.021). Control patients had an increased risk of gram-negative septicemia (relative risk = 2.65, P = 0.0039) and local infection (relative risk = 1.36, P = 0.029) and received 51 more units of platelets than did immunoglobulin recipients. Neither survival nor the risk of relapse was altered by immunoglobulin. However, among patients greater than or equal to 20 years old, there was a reduction in the incidence of acute GVHD (51 percent in controls vs. 34 percent in immunoglobulin recipients; P = 0.0051) and a decrease in deaths due to transplant-related causes after transplantation of HLA-identical marrow (46 percent vs. 30 percent; P = 0.023).\n Passive immunotherapy with intravenous immunoglobulin decreases the risk of acute GVHD, associated interstitial pneumonia, and infections after bone marrow transplantation.", "Sixty-three patients with crescentic glomerulonephritis (cellular crescents in greater than 50% of glomeruli) were considered for a prospective randomized trial comparing intravenous methylprednisolone, prednisone, and azathioprine with and without plasma exchange. Of 32 patients who fulfilled the inclusion criteria for this study, 16 were randomly assigned to receive drug therapy (control) and 16 to receive plasma exchange as well. The randomization was stratified for initial need of dialysis, and the presence of oliguria and sclerosis. Renal pathology was similar in the two groups of patients. There was no significant difference in the number of patients initially on dialysis who were able to discontinue it during the study (2/7 control v 3/4 plasma exchange), whereas no control but two plasma exchange-treated patients started dialysis during the study. Serum creatinine at randomization was similar in the two groups: 769 +/- 486 mumol/L (8.7 +/- 5.5 mg/dL) in the control group versus 643 +/- 275 mumol/L (7.3 +/- 3.1 mg/dL) in the plasma exchange group. There was no significant difference between the two groups in mean serum creatinine, change in serum creatinine, change in reciprocal, or change in logarithm of serum creatinine at 1, 3, 6, or 12 months following randomization. Power calculation, assuming a 20% difference would be clinically relevant, was 0.94 at 12 months. There was significant morbidity in both groups; there were two deaths within 1 year of randomization, both of pulmonary infection and both in the plasma exchange group. We conclude that plasma exchange offers no additional therapeutic benefit to patients with idiopathic rapidly progressive glomerulonephritis (RPGN) who are not dialysis-dependent at presentation." ]

[ "16517193", "16246996", "12365880", "17632223", "18441375", "17530112", "9337378", "17577801", "17624979" ]

[ "A controlled trial of nortriptyline, sustained-release bupropion and placebo for smoking cessation: preliminary results.", "Efficacy of bupropion and nortriptyline for smoking cessation among people at risk for or with chronic obstructive pulmonary disease.", "Psychological intervention and antidepressant treatment in smoking cessation.", "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.", "Nortriptyline plus nicotine replacement versus placebo plus nicotine replacement for smoking cessation: pragmatic randomised controlled trial.", "A randomized trial of smoking cessation. Medication versus motivation.", "A comparison of sustained-release bupropion and placebo for smoking cessation.", "Bupropion and cognitive-behavioral treatment for depression in smoking cessation.", "A randomized trial of bupropion and/or nicotine gum as maintenance treatment for preventing smoking relapse." ]

[ "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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." ]

[ "17055767", "16269638", "15827910", "9550512", "15774435", "15066200", "11545671", "9037575", "21436390" ]

[ "Effectiveness of physiotherapy in Parkinson's disease: the feasibility of a randomised controlled trial.", "Facilitation of sensory and motor recovery by thermal intervention for the hemiplegic upper limb in acute stroke patients: a single-blind randomized clinical trial.", "Efficacy of a physical therapy program in patients with Parkinson's disease: a randomized controlled trial.", "Effect of a therapeutic intervention for the hemiplegic upper limb in the acute phase after stroke: a single-blind, randomized, controlled multicenter trial.", "Comparison of Bobath based and movement science based treatment for stroke: a randomised controlled trial.", "An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].", "A randomized effectiveness trial of collaborative care for patients with panic disorder in primary care.", "Early combination of bromocriptine and levodopa in Parkinson's disease: a prospective randomized study of two parallel groups over a total follow-up period of 44 months including an initial 8-month double-blind stage.", "Effects of treatment intensity in upper limb robot-assisted therapy for chronic stroke: a pilot randomized controlled trial." ]

[ "To study the feasibility of a large randomised controlled trial (RCT) evaluating the effectiveness of physiotherapy in Parkinson's disease (PD), 173 patients were asked to participate in a study with random allocation to best practice physiotherapy, or to no physiotherapy. The primary outcome measures were the Parkinson's disease questionnaire-39, the Parkinson activity scale, and a patient preference outcome scale (PPOS). Only 14% of the patients could be included in the study. The PPOS showed the largest effect size (0.74) with a significant group effect (p<0.05). Specific alterations to the study design to ensure successful RCTs in this field are recommended.", "Thermal stimulation (TS) is commonly used in orthopedic rehabilitation, but the role of TS in the facilitation of sensorimotor recovery in hemiplegic patients remains unknown. This study addressed the issue of TS intervention in the facilitation of functional outcomes.\n Forty-six stroke survivors were randomly assigned to standard rehabilitation treatment and standard treatment plus TS (30 minutes daily for 6 weeks). Twenty-nine patients completed the experiment. Six measures, including Brunnstrom stage, modified motor assessment scale, grasping strength, angles of wrist extension and flexion, sensation by monofilament, and muscle tone by modified Ashworth scale, were performed weekly to evaluate sensory and motor functional outcomes.\n The performance of Brunnstrom stage and wrist extension and sensation were improved significantly after TS intervention. Recovery rates of 6 measures after TS were significantly higher than those of the control, except for grasping. Similar muscle tones were found in both groups.\n TS on the paretic hand significantly enhances the recovery of several aspects of sensory and motor functions in hemiplegic stroke patients.", "To investigate the effects of a physical therapy (PT) program in groups of people with Parkinson's disease (PD).\n Randomized controlled trial with a crossover design.\n Two outpatient rehabilitation clinics in Boston and Amsterdam, respectively.\n Sixty-eight subjects diagnosed with typical, idiopathic PD, Hoehn and Yahr stage II or III, and stable medication use.\n Group A received PT and medication therapy (MT) for the first 6 weeks, followed by MT only for the second 6 weeks. Group B received only MT for the first 6 weeks and PT and MT for the second 6 weeks.\n The Sickness Impact Profile (SIP-68), the mobility portion of the SIP-68, the Unified Parkinson's Disease Rating Scale (UPDRS), and comfortable walking speed (CWS) at baseline, 6-week, 12-week, and 3-month follow-up.\n At 6 weeks, differences between groups were significant for the SIP mobility ( P =.015; effect size [ES]=.55), for CWS ( P =.012; ES=.49), for the activities of daily living (ADL) section of the UPDRS ( P =.014; ES=.45), and for the total UPDRS ( P =.007; ES=.56). The total SIP and the mentation and motor sections of the UPDRS did not differ significantly between groups. Significant differences were found at 3 months compared with baseline for CWS, the UPDRS ADL, and total scores.\n People with PD derive benefits in the short term from PT group treatment, in addition to their MT, for quality of life related to mobility, CWS, and ADLs; long-term benefits were found in CWS, UPDRS ADL, and total scores but varied between groups.", "Arm function recovery is notoriously poor in stroke patients. The effect of treatment modalities, particularly those directed at improving upper limb function, has been studied primarily in chronic stroke patients. The purpose of this study was to investigate the effect of a specific therapeutic intervention on arm function in the acute phase after stroke.\n In a single-blind, randomized, controlled multicenter trial, 100 consecutive patients were allocated to either an experimental group that received an additional treatment of sensorimotor stimulation or to a control group. The intervention was applied for 6 weeks. Patients were evaluated for level of impairment (Brunnström-Fugl-Meyer test) and disability (Action Research Arm test, Barthel Index) before, midway, and after the intervention period and at follow-up 6 and 12 months after stroke.\n Patients in the experimental group performed better on the Brunnström-Fugl-Meyer test than those in the control group throughout the study period, but differences were significant only at follow-up. Results on the Action Research Arm test and Barthel Index revealed no effect at the level of disability. The effect of the therapy was attributed to the repetitive stimulation of muscle activity. The treatment was most effective in patients with a severe motor deficit and hemianopia or hemi-inattention. No adverse effects due to the intervention were found.\n Adding a specific intervention during the acute phase after stroke improved motor recovery, which was apparent 1 year later. These results emphasize the potential beneficial effect of therapeutic interventions for the arm.", "Bobath based (BB) and movement science based (MSB) physiotherapy interventions are widely used for patients after stroke. There is little evidence to suggest which is most effective. This single-blind randomised controlled trial evaluated the effect of these treatments on movement abilities and functional independence.\n A total of 120 patients admitted to a stroke rehabilitation ward were randomised into two treatment groups to receive either BB or MSB treatment. Primary outcome measures were the Rivermead Motor Assessment and the Motor Assessment Scale. Secondary measures assessed functional independence, walking speed, arm function, muscle tone, and sensation. Measures were performed by a blinded assessor at baseline, and then at 1, 3, and 6 months after baseline. Analysis of serial measurements was performed to compare outcomes between the groups by calculating the area under the curve (AUC) and inserting AUC values into Mann-Whitney U tests.\n Comparison between groups showed no significant difference for any outcome measures. Significance values for the Rivermead Motor Assessment ranged from p = 0.23 to p = 0.97 and for the Motor Assessment Scale from p = 0.29 to p = 0.87.\n There were no significant differences in movement abilities or functional independence between patients receiving a BB or an MSB intervention. Therefore the study did not show that one approach was more effective than the other in the treatment of stroke patients.", "The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.\n Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.\n Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of \"as required\" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients \"at risk of stroke\" on aspirin at follow-up.\n While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained.", "Effectiveness studies have tested interventions to improve quality of care for depression in primary care, but none, to our knowledge, have been completed for panic disorder (PD) in this setting. This study sought to test the clinical effectiveness of PD pharmacotherapy embedded in a disease management framework of \"collaborative care\" (CC).\n One hundred fifteen patients with PD from 3 primary care clinics were randomized to CC or \"usual care\" (UC). Patients in CC (n = 57) received educational videotapes and pamphlets; pharmacotherapy with the selective serotonin reuptake inhibitor paroxetine; 2 psychiatrist visits and 2 telephone calls in the first 8 weeks; and up to 5 telephone calls between 3 and 12 months' follow-up. Usual care patients (n = 58) were treated by their primary care physician. Telephone assessments of panic, anxiety sensitivity, depression, and disability variables were performed at 3, 6, 9, and 12 months' follow-up. Adequacy of pharmacotherapy was assessed with an algorithm based on a review of efficacy studies.\n Patients in CC were more likely to receive adequate (type, dose, duration) medication and more likely to adhere to this medication at 3 and 6 months. Random regression analyses showed that CC patients improved significantly more over time compared with UC patients on anxiety, depression, and disability measures, with the greatest effects at 3 and 6 months.\n Compared with UC, CC interventions significantly improved both quality of care and clinical and functional outcomes in primary care PD patients. Clinical differences were greatest in the first 6 months, corresponding to the greater quality of care and the greater intensity of intervention.", "To determine if the combination of levodopa (LD) plus bromocriptine (Br) in the early stages of Parkinson's disease (PD) permits reduction of LD dosage and consequently results in fewer motor fluctuations and dyskinesias, a double-blind, multicenter prospective study in 50 PD patients who had responded favorably to LD while under treatment with that drug for < or = 6 months was undertaken. Patients were randomized into two parallel groups (LD alone and LD plus Br). During the first placebo-controlled stage of the study lasting 8 months, association of a fixed dose of Br (15 mg/day) in the LD regimen did not allow a significant reduction in the daily LD dose. Still, in patients on combined LD plus Br, there was a tendency toward smaller daily requirements of LD as compared with those on LD alone, and the difference in LD dose between the two groups was significantly different (515.4 +/- 240 vs. 725.6 +/- 230 mg/day; p < 0.01) after 44 months of continuous treatment in the 40 patients still enrolled in the open-label stage. At that point in time, the mean dose of Br had been increased by 9.2 mg in the combined treatment group, and the mean dose of LD was 40.7% lower than in the group receiving LD alone. On subsequent evaluations, the number of patients with dyskinesias or describing wearing-off fluctuations severe enough to require changes in treatment was lower than in the group under combined therapy, the differences being significant after 20 and 44 months, respectively (36.8 vs. 9.5 and 47.3 vs. 14.2%). Our results support early combined LD-Br therapy in PD, but no conclusions can be drawn as to whether this dopamine agonist exerts a preventive effect on the late side effects of LD or has another mechanism of action.", "Robot-assisted therapy (RT) is a current promising intervention in stroke rehabilitation, but more research is warranted for examining its efficacy and the dose-benefit relation. The authors investigated the effects of higher intensity versus lower intensity RT on movements of forearm pronation-supination and wrist flexion-extension relative to conventional rehabilitation (CR) in patients poststroke for a mean of 21 months.\n In this pilot study, 18 patients with initial mean Fugl-Meyer Assessment (FMA) of 37 to 44 for the upper extremity were randomized to higher intensity RT, lower intensity RT, or CR intervention for 4 weeks. The dose of the higher intensity RT was twice the number of repetitions in the lower intensity RT. Outcome measures at pretreatment and posttreatment were administered to patients to evaluate beneficial and adverse effects of interventions. Primary outcomes were the FMA and Medical Research Council scale.\n There were significant differences in motor function (P = .04) and daily performance (P = .03) among the 3 groups. The higher intensity RT group showed better improvement in motor function, muscle strength, performance of daily activities, and bimanual ability than the other 2 groups. The intensive RT intervention did not induce higher levels of an oxidative DNA biomarker.\n Higher intensity of RT that assists forearm and wrist movements may lead to greater improvement in motor ability and functional performance in stroke patients. A sample size of only 20 to 25 in each arm of a larger randomized controlled trial is needed to confirm the findings for similar subjects." ]

[ "11113837", "8813983", "3234607", "9797593", "8957948", "16541716", "12674840", "15670265", "2299491" ]

[ "Lack of benefit of laxatives as adjunctive therapy for functional nonretentive fecal soiling in children.", "Biofeedback training in treatment of childhood constipation: a randomised controlled study.", "Biofeedback training for patients with myelomeningocele and fecal incontinence.", "Randomised controlled trial of biofeedback training in persistent encopresis with anismus.", "Randomised trial of biofeedback training for encopresis.", "[Usefulness of biofeedback treatment in children with chronic functional constipation].", "Efficiency of biofeedback therapy for chronic constipation in children.", "A randomized-controlled trial comparing an educational intervention alone vs education and biofeedback in the management of faecal incontinence in women.", "Modulation of abnormal defecation dynamics by biofeedback treatment in chronically constipated children 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.", "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.", "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.", "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.", "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.", "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.", "Biofeedback (BF) training is an accepted therapy in the treatment of faecal incontinence (FI) despite a paucity of data demonstrating benefit. This study aims to determine whether BF has any specific effect above and beyond an educational intervention. Twenty-three women with regular and frequent idiopathic FI were randomized to education and pelvic exercise vs education and BF therapy. Complete data is available for 18 women. Overall, 61% of participants demonstrated a complete response. There was no difference in response rate between treatment arms. Women with FI demonstrate a good response to treatment with education and exercise and education plus BF thus questioning the specific effect of BF.", "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." ]

[ "12648639", "12353900", "17318205", "17202203", "10216048", "9159691", "1927314", "2668133", "9113011" ]

[ "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.", "Posterior capsule opacification after extra capsular cataract extraction in Indian rural population: foldable acrylic vs poly (methyl-methacrylate) intraocular lenses a randomized clinical trial.", "Long-term results of sealed capsule irrigation using distilled water to prevent posterior capsule opacification: a prospective clinical randomised trial.", "Randomised clinical trial of lensectomy versus lens aspiration and primary capsulotomy for children with bilateral cataract in south India.", "Heparin eyedrops to prevent posterior capsule opacification.", "Factors influencing the formation of posterior capsular opacities after extracapsular cataract extraction with posterior chamber lens implant.", "[Postoperative cataract following intraocular lenses with and without laser ridge].", "Randomised controlled trial of anterior-chamber intraocular lenses." ]

[ "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.", "To compare the performance of single-piece acrylic vspoly (methylmethacrylate) intraocular lenses (IOL) on the development of posterior capsule opacification (PCO) after conventional extra capsular cataract extraction (ECCE).\n One hundred and eighty-two eyes of 91 patients with bilateral senile cataract undergoing ECCE were prospectively randomized to receive a single-piece Alcon AcrySof SA60AT IOL or a single-piece EPOCH polymethylmethacrylate IOL in the first eye to have surgery. At 1, 6 and 12 months post-operative follow-up, digital retro illumination images of the posterior capsule were taken for PCO assessment semi-objectively using PCO (POCO automated analysis software) system. Relationship of anterior capsule contact (total off and partial cover) on optic for PCO was analyzed.\n The AcrySof IOL was associated with less PCO than EPOCH lens at 6 months (10.01+/-8.75% vs 32.26+/-27.44%; P<0.001) and 1-year (11.65+/-10.55% vs 38.38+/-29.62%; P<0.001) follow-up. The EPOCH IOL showed a remarkably significant difference on development of PCO with anterior capsule overlap on IOL optic (total off and part on) 1 year (P<0.039), whereas no such difference was observed with the AcrySof IOL (P=0.197).\n The AcrySof IOL led to significantly less PCO than the EPOCH IOL post-operatively after extracapsular cataract extraction.", "We investigated long-term safety and efficacy of sealed capsule irrigation (SCI) during cataract surgery to prevent posterior capsule opacification (PCO).\n One eye of each of 17 patients (mean age: 70.1+/-9.7 years) who presented with bilateral cataracts was randomly chosen for SCI treatment. After phacoemulsification, the capsular bag was vacuum sealed with the PerfectCapsule device (Milvella) followed by SCI using distilled water for two minutes. No vacuum loss occurred during irrigation. Each patient's fellow eye served as a control. One hydrophilic acrylic intraocular lens model was implanted in all eyes. Five patients had to be excluded due to deep anterior chamber, small pupil or unilateral surgery. Follow-up examinations took place one day and one, three, six, 12 and 24 months after surgery. We evaluated safety parameters, anterior capsule (AC) overlapping and PCO.\n Postoperatively, mean best corrected visual acuity, pachymetry, endothelial cell count, intraocular pressure, AC overlapping and PCO showed no statistically significant difference between SCI and the control group (p>0.05, Wilcoxon test).\n SCI is a safe procedure and enables the specific pharmacological targeting of lens epithelial cells inside the capsular bag. Using distilled water, however, it is not possible to reduce PCO development significantly. Thus, alternative substances should be evaluated.", "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 whether heparin eyedrops prevent or reduce posterior capsule opacification (PCO) after extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation.\n Institute of Ophthalmology, University G. d'Annunzio, Chieti, Italy.\n This 4 year, prospective, case-controlled study evaluated 200 patients who had ECCE and implantation of the same type of posterior chamber IOL. Patients were randomly assigned to receive topical heparin eyedrops postoperatively (heparin group, n = 100) or not to receive the eyedrops (control group, n = 100). Postoperative cell response, cellular precipitates on the IOL, and presence of PCO were evaluated.\n There were no significant differences between groups in postoperative inflammation. The incidence of cellular precipitates was significantly lower in the heparin group than in the control group (P < .001). A neodymium:YAG (Nd:YAG) posterior capsulotomy was done in 7 patients in the heparin group and 14 in the control group (P = .15). During the first 24 months after surgery, the heparin group had a significantly lower incidence of Nd:YAG capsulotomy (P < .05) and fibrotic PCO (P = .02).\n Topical heparin eyedrops were effective in reducing fibrotic PCO in the long term, indicating their usefulness in the postoperative management of ECCE.", "This study was designed to determine whether different factors could influence the formation of posterior capsular opacities. The study group comprised 271 patients who had undergone an extracapsular cataract extraction with implantation of a posterior chamber lens either with or without laser ridge. Between 12 and 25 months after surgery, a statistically significant difference was found with a lower rate of secondary cataract in the laser ridge group, but with respect to advanced secondary cataract, i.e. eyes which needed YAG capsulotomy, no statistically significant difference was found (P-value 0.99). No association was found between age or sex of patients, different surgeons or complications during or after surgery and the risk of getting a secondary cataract.", "In this randomized, prospective clinical study, a convex plane intraocular lens (IOL) with a laser ridge was compared with a convex plane IOL without a laser ridge. No difference was found in the reduction of capsular opacification 1 year after surgery. The 100 patients (40 males/60 females) with senescent cataracts were treated with ECCE by a single surgeon from November 1986 to March 1987. The operative technique consisted of capsulorhexis, irrigation-aspiration and in-the-bag-implantation. The first group of 50 patients (50 eyes) had an IOL without a laser ridge and the second group an IOL with a laser ridge. When considering after-cataracts in combination with minor visual deterioration we had secondary cataract rate of 15% in the IOL group with a laser ridge and of 16% in the IOL group without a laser ridge. When we considered only the cases in which visual acuity worsened and YAG laser capsulotomy was required, the secondary cataract rate was 1.5%.", "There are an estimated 16 million people blind in both eyes with cataracts. Most live in rural areas of developing countries where surgical resources are scarce. There is no consensus on the most appropriate type of intraocular lens in situations where high-volume low-cost surgery is required. This study was undertaken to evaluate the safety of multiflex open-loop anterior-chamber lenses (ACIOLs).\n 2000 people attending Lahan Eye Hospital, southern Nepal, with bilateral cataracts reducing vision to 6/36 or less were randomly allocated to receive standard surgery--intracapsular extraction (ICCE) with aphakic correction--or ICCE with an ACIOL in their first operated eye. The primary outcome was a visual acuity of less than 6/60 in the operated eye at 1 year follow-up. Visual acuity was measured for 91% of the cohort at 1 year. The sample size was estimated to detect a doubling in poor visual outcome from an estimated rate of 4% in the standard surgery (control) group.\n The median (range) time taken to do the surgery was 6.0 (3.0-17.2) min for the ACIOL group and 4.1 (2.4-10.3) min for the control group. 1 year after surgery, 5.0% of the ACIOL group and 5.4% of controls had functional vision less than 6/60 (OR 0.93 [0.60-1.43], p = 0.71). The causes of poor vision in the ACIOL and control groups were: correctable refractive error (22 and 29), uveitis/secondary glaucoma (13 and two), endophthalmitis (four and seven), pre-existing eye disease (four and five), retinal detachment (none and four), cystoid macular oedema (two and none), corneal ulcer (one and one), and corneal decompensation (none and one).\n This study provides evidence that, in rural areas of developing countries, multiflex open-loop ACIOLs can be implanted safely by experienced ophthalmologists after routine ICCE, avoiding the disadvantages of aphakic spectacle correction. Further follow-up is planned." ]

[ "8464671", "3935013", "1615179", "7930301", "18475602", "10582197", "3929698", "413493", "4398782" ]

[ "Failure of cromolyn sodium to reduce the incidence of bronchopulmonary dysplasia: a pilot study. The Neonatal Cromolyn Study Group.", "A controlled study of education for improving compliance with cromolyn sodium (Intal): the importance of physician-patient communication.", "Inhaled sodium cromoglycate for pre-term children with respiratory symptoms at follow-up.", "Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children.", "The Effect of Cromolyn Sodium and Nedocromil Sodium Administered by A pressurized Aerosol with A spacer Device on Exercise-Induced Asthma in Children.", "Comparison of two different dose regimens of nedocromil sodium with placebo in the management of childhood asthma.", "Nebulised sodium cromoglycate in recurrently wheezy preschool children.", "Nebulized sodium cromoglycate in young asthmatic children. Double-blind trial.", "Effect of cromolyn sodium on childhood asthma." ]

[ "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.", "The effectiveness of an educational program to increase compliance with cromolyn sodium was assessed in 31 children and adolescents 6 to 17 years of age. Patients were randomly assigned to an education or noneducation group. A standard education program regarding asthma and asthma medications was provided to the education group during four monthly visits. At each visit, all patients were assessed in terms of knowledge of asthma and medications, asthma-related symptoms, and pulmonary function. Patients were also asked to self-rate their compliance. The education program increased the patients' knowledge of cromolyn, and appeared to result in increased cromolyn compliance. Post-hoc analyses, however, suggested that increased compliance did not correspond to improved medical status unless the quality of management (by physician and parents) of the child's asthma was taken into account. These results suggest that inadequate management of asthma in children may be a more serious problem than patient noncompliance.", "Children born prematurely frequently have recurrent respiratory symptoms at follow-up and benefit from bronchodilator therapy. We have assessed if regular inhaled sodium cromoglycate would reduce this respiratory morbidity and need for bronchodilator therapy. Sixteen symptomatic children (median gestational age 29 weeks, post-natal age 15 months) were entered into a randomized double-blind, placebo-controlled trial. In two 3-week periods, the patients received either placebo or sodium cromoglycate (5 mg) as one puff q.d.s. from an inhaler via a coffee cup. Parents recorded their child's symptoms and need for bronchodilator therapy throughout and lung function was assessed by measurement of functional residual capacity (FRC) at the beginning and end of each 3-week period. The symptom score was reduced by 49% in the active compared to the placebo period (P less than 0.01) and bronchodilator was taken on a mean of 2.9 days per infant in the active period compared to 7.9 days in the placebo period (P less than 0.01). There was a significant improvement in FRC in ten of 16 patients over the active period but only in two infants over the placebo period (P less than 0.01). We conclude regular inhaled sodium cromoglycate is useful prophylaxis for symptomatic pre-term children.", "Seventeen children with asthma were studied in a double-blind, crossover, placebo-controlled study designed to compare the efficacy of cromolyn sodium with that of nedocromil sodium in preventing exercise-induced asthma. All drugs were delivered through a metered-dose inhaler (cromolyn sodium, 10 mg; nedocromil sodium, 4 mg; placebo, two puffs). Nedocromil sodium and cromolyn sodium provided significant, comparable protection from exercise-induced asthma, and both drugs were better than placebo. We conclude that nedocromil sodium and cromolyn sodium administered by a pressurized aerosol provide equal protection against exercise-induced asthma in children.", "To compare the effectiveness of cromolyn sodium (CS) (10 mg) and nedocromil sodium (NS) (4 mg) administered by a metered dose inhaler (MDI) with a spacer device in preventing exercise-induced asthma (EIA), eight asthmatic children with EIA were studied in a randomized double-blind, cross-over, placebo-controlled study, CS and NS provided significant, comparable protection from EIA and both were better than placebo. We conclude that CS and NS administered by a pressurized aerosol with a spacer device provide equal protection against EIA in children.", "According to the recent guidelines, persistent asthma requires daily antiinflammatory treatment with either nedocromil sodium, cromolyn sodium or inhaled corticosteroids. In choosing the most appropriate drug, it is wise to weigh the therapeutic advantages against possible side effects, particularly in patients at the milder end of disease spectrum and in children. Cromolyn sodium and nedocromil sodium both have strong safety profiles, and nedocromil sodium has been reported to have a broader spectrum of efficacy than cromolyn sodium. In an attempt to provide data for the efficacy of two different dose regimens of inhaled nedocromil sodium in childhood asthma, a placebo-controlled, randomized, double-blind, double-dummy, parallel group study was conducted in 38 subjects with mild to moderate persistent asthma. After a 2-week run-in period, patients were randomly allocated into one of the three study groups and treated with either placebo or with two times daily (4 mg b.i.d.) or four times daily (4 mg q.i.d.) regimens of inhaled nedocromil sodium for 8 weeks. Symptom scores, bronchodilator requirements, FEV1, daily PEFs and methacholine hyperreactivity were evaluated at study entry, before randomization and at weeks 4 and 8 of treatment. In the four times daily treatment group, slight but significant increases were observed in FEV1, peak expiratory flows and symptom scores (p < 0.05 for each). However, there was no significant change in methacholine hyperreactivity and bronchodilator requirement. In the two times dose regimen and placebo groups, there were no improvements in any of the variables. The compliance, measured as the reduced weight of the canisters, was low, but was not different between the two nedocromil sodium treatment groups. The four times daily regimen of nedocromil sodium was effective in improving control of mild to moderate persistent asthma in children, whereas the two times daily regimen failed.", "A double blind crossover study of nebulised sodium cromoglycate in 27 asthmatic preschool children was carried out over a one year period. All subjects had sufficiently severe asthma to have had at least one admission to hospital. The active treatment was sodium cromoglycate 20 mg (in 2 ml) administered by a nebuliser four times daily. Assessment was made by a diary card and clinical examination. Results were analysed in 24 subjects who completed the study. Statistical analysis allowed for order of treatment and seasonal effects. Significant results in favour of treatment with sodium cromoglycate were obtained for night cough, day activity, percentage of symptom free days, and overall severity of asthma. During active treatment there was no reduction in the rate of admissions to hospital or intravenous drugs used. The wheeze score during the week after an upper respiratory tract infection was not reduced during treatment with sodium cromoglycate. Nebulised sodium cromoglycate is a tedious prophylactic treatment for the young asthmatic child but is useful when other treatments have failed.", "Seventeen asthmatic children under 5 years of age took part in a double-blind controlled trial of nebulized sodium cromoglycate solution. Daily symptom scores kept by the parents showed improvement in 11 children during active treatment, and a significant improvement in scores for cough by day and night was obtained for the group as a whole.", "nan" ]

[ "8270972", "10819701", "16139656", "11896107", "18359433", "15520472", "15663589", "17565936", "22030384" ]

[ "Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.", "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 randomized controlled trial of relaxation training to reduce hot flashes in women with primary breast cancer.", "The impact of the Women's Health Initiative study on incident clonidine use in Ontario, Canada.", "The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial.", "Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial.", "Effects of tibolone on climacteric symptoms and quality of life in breast cancer patients--data from LIBERATE trial." ]

[ "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.", "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.", "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.", "Following publication of the Women's Health Initiative (WHI) study, many women discontinued use of estrogen replacement therapy. There is some evidence that the antihypertensive agent clonidine can reduce the frequency of hot flashes associated with menopause.\n To determine the impact of the WHI study on incident use of clonidine in elderly women in Ontario, Canada.\n Retrospective, population-based administrative database design. Data on all residents of Ontario over the age of 65 years were included. Time series methods were used to analyze change in incident clonidine use following publication of the WHI study.\n Following publication of the WHI study, incident use of clonidine increased substantially among elderly women in Ontario, Canada. Similar trends were not observed for incident use of other antihypertensive medications.\n During a period of time in which a large proportion of women discontinued estrogen replacement therapy, incident use of clonidine increased. There is some evidence that a small number of women may have sought alternative relief from menopausal symptoms using other pharmacological therapies.", "To assess the effects of tibolone on climacteric symptoms, endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer.\n Double-blind, randomised, placebo-controlled, multicentre pilot study.\n Hospital outpatient clinic.\n Seventy postmenopausal women receiving tamoxifen following surgery for early breast cancer.\n Women received 20 mg/day oral tamoxifen plus either 2.5 mg/day oral tibolone or placebo for 12 months.\n Frequency and severity of hot flushes (diary cards); intensity of hot flushes and sweats (Landgren scale); interference of hot flushes and sweats with normal life; frequency and intensity of other climacteric symptoms; endometrial thickness and histology; vaginal bleeding; breast cancer recurrence and serum lipid/lipoproteins.\n Daily card data showed no change in the daily number of hot flushes with either tibolone or placebo (P= 0.219) after three months. There was a significant reduction in the severity of flushes with tibolone compared with placebo (-0.4 vs 0.2, P= 0.031). The Landgren scale showed a mean change in the number of hot flushes of -0.6 with tibolone and +1.1 with placebo after 12 months (P= 0.022). Endometrial biopsies were normal and vaginal bleeding was similar in both groups. A significant decrease in triglycerides (-23% vs 1.4%) and HDL (-12% vs 19%) was seen with tibolone compared with placebo after 12 months.\n Tibolone prevented an increase in hot flushes in postmenopausal women given tamoxifen following surgery for breast cancer without untoward effects on the endometrium. Beneficial effects on serum lipid profile were noted.", "The objective of this study was to evaluate the efficacy of fluoxetine and black cohosh in the treatment of women with postmenopausal symptoms. A total of 120 healthy women with menopausal symptoms were recruited to this prospective study with a follow-up period of 6 mo. They were randomly assigned to 1 of 2 groups and were treated with fluoxetine or black cohosh. After entry into the study, patients were examined at the first, second, third, and sixth months of the treatment period. The women kept diaries in which they reported the daily number and intensity of hot flushes and night sweats. In addition, at the beginning and end of the third month, they completed questionnaires consisting of a modified Kupperman Index, Beck's Depression Scale, and a RAND-36 Quality-of-Life Questionnaire. Statistically significant differences were noted in the Kupperman Index and Beck's Depression Scale at the end of the third month in both groups compared with baseline values. In the black cohosh group, the Kupperman Index decreased significantly compared with that in the fluoxetine group by the end of the third month. On the other hand, in the fluoxetine group, Beck's Depression Scale decreased significantly compared with that in the black cohosh group. Monthly scores for hot flushes and night sweats decreased significantly in both groups; however, black cohosh reduced monthly scores for hot flushes and night sweats to a greater extent than did fluoxetine. At the end of the sixth month of treatment, black cohosh reduced the hot flush score by 85%, compared with a 62% result for fluoxetine. By the sixth month of the study, 40 women had discontinued the study--20 (33%) in the fluoxetine group and 20 (33%) in the black cohosh group. Compared with fluoxetine, black cohosh is more effective for treating hot flushes and night sweats. On the other hand, fluoxetine is more effective in improvements shown on Beck's Depression Scale.", "Climacteric symptoms such as hot flushes and vaginal dryness are very common in breast cancer patients, resulting either from age or adjuvant therapy. Tibolone, a synthetic steroid, is effective in reducing these symptoms in healthy post-menopausal women, but this has never been studied in a large breast cancer population.\n The primary objective of LIBERATE trial was to study safety of tibolone 2.5mg daily versus placebo as primary, in symptomatic breast cancer survivors. The aim of this present paper was to report effects of tibolone on climacteric symptoms, vaginal dryness and health-related quality of life in the study population. This trial is registered with ClinicalTrials.gov, n. NCT00408863.\n The trial was conducted between June 2002 and July 2007. Concerning quality of life variables, a daily Diary Cards during the first three months and the Climacteric Symptoms Form and at each visit were used to register frequency and intensity of hot flushes. Mean vaginal dryness scores were calculated on the basis of individual ratings at baseline and at week 104. A subset of patients assessed their quality of life filling in the Women's Health Questionnaire (WHQ).\n Of the 3148 women recruited, 3133 received trial medication (1575 in the tibolone group and 1558 in the placebo group). The median duration of treatment was 2.75 years. In total 3098 women (1556 on tibolone, 1542 on placebo) were included in the intention-to-treat (ITT) population for efficacy analysis. Data on vaginal dryness are available for 2144 patients and 883 women (438 on tibolone, 445 on placebo) answered to WHQ. The mean change in number of hot flushes per day was 2.74 (43.1%) in the tibolone group and -1.77 (-27.5%) in the placebo group (p<0.0001) at week 12 and -4.62 (-65.6%) on tibolone as compared to -3.73 (-52.5%) on placebo (p<0.0001) at week 104. For the composite score the mean changes at week 12 were -0.19 (-10.6%) and -0.14 (-7.7%), respectively (p=0.0006). Vaginal dryness score improved at week 104 in the tibolone group as compared to placebo (-0.46 versus -0.29, respectively; p<0.0001). Across the assessments up to two years with WHQ, tibolone was more effective than placebo in improving sexual health, sleep quality and mood domains. Women using tamoxifen showed less improvement in climacteric symptoms with tibolone, than women only receiving tibolone without any adjuvant therapy.\n The results of the LIBERATE trial show that tibolone is effective in symptomatic breast cancer patients and improves their quality of life. However, this finding should be judged within the context of the main outcome of the trial, showing that tibolone increases the risk of recurrence. The use of tibolone in women with breast cancer will remain contraindicated and any off-label use incurs a now proven risk.\n Copyright © 2011 Elsevier Ireland Ltd. All rights reserved." ]

[ "10473306", "9328501", "14702229", "17924246", "20181120", "9803707", "12611847", "12765500", "2571625" ]

[ "A randomized controlled trial of individual psychological debriefing for victims of violent crime.", "Randomised controlled trial of psychological debriefing for victims of acute burn trauma.", "Early cognitive-behavioural therapy for post-traumatic stress symptoms after physical injury. Randomised controlled trial.", "Trial of interpersonal counselling after major physical trauma.", "Effectiveness of a single-session early psychological intervention for children after road traffic accidents: a randomised controlled trial.", "Treatment of acute stress disorder: a comparison of cognitive-behavioral therapy and supportive counseling.", "Treating acute stress disorder following mild traumatic brain injury.", "Stress debriefing after childbirth: a randomised controlled trial.", "Brief psychotherapy for posttraumatic stress disorders." ]

[ "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.", "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.", "Early single-session psychological interventions, including psychological debriefing following trauma, have not been shown to reduce psychological distress. Longer early psychological interventions have shown some promise.\n To examine the efficacy of a four-session cognitive-behavioural intervention following physical injury.\n A total of 152 patients attending an accident and emergency department displaying psychological distress following physical injury were randomised 1-3 weeks post-injury to a four-session cognitive-behavioural intervention that started 5-10 weeks after the injury or to no intervention and then followed up for 13 months.\n At 13 months, the total Impact of Event Scale score was significantly more reduced in the intervention group (adjusted mean difference=8.4,95% CI 2.4-14.36). Other differences were not statistically significant.\n A brief cognitive-behavioural intervention reduces symptoms of post-traumatic stress disorder in individuals with physical injury who display initial distress.", "The purpose of the present study was to determine if interpersonal counselling (IPC) was effective in reducing psychological morbidity after major physical trauma.\n One hundred and seventeen subjects were recruited from two major trauma centres and randomized to treatment as usual or IPC in the first 3 months following trauma. Measures of depressive, anxiety and post-traumatic symptoms were taken at baseline, 3 months and 6 months. The Structured Clinical Interview for DSM IV diagnoses was conducted at baseline and at 6 months to assess for psychiatric disorder.\n Fifty-eight patients completed the study. Only half the patients randomized to IPC completed the therapy. At 6 months the level of depressive, anxiety and post-traumatic symptoms and the prevalence of psychiatric disorder did not differ significantly between the intervention and treatment-as-usual groups. Subjects with a past history of major depression who received IPC had significantly higher levels of depressive symptoms at 6 months.\n IPC was not effective as a universal intervention to reduce psychiatric morbidity after major physical trauma and may increase morbidity in vulnerable individuals. Patient dropout is likely to be a major problem in universal multi-session preventative interventions.", "Road traffic accidents (RTAs) are the leading health threat to children in Europe, resulting in 355,000 injuries annually. Because children can suffer significant and long-term mental health problems following RTAs, there is considerable interest in the development of early psychological interventions. To date, the research in this field is scarce, and currently no evidence-based recommendations can be made.\n To evaluate the effectiveness of a single-session early psychological intervention, 99 children age 7-16 were randomly assigned to an intervention or control group. The manualised intervention was provided to the child and at least one parent around 10 days after the child's involvement in an RTA. It included reconstruction of the accident using drawings and accident-related toys, and psychoeducation. All of the children were interviewed at 10 days, 2 months and 6 months after the accident. Parents filled in questionnaires. Standardised instruments were used to assess acute stress disorder (ASD), posttraumatic stress disorder (PTSD), depressive symptoms and behavioural problems.\n The children of the two study groups showed no significant differences concerning posttraumatic symptoms and other outcome variables at 2 or at 6 months. Interestingly, analyses showed a significant intervention x age-group effect, indicating that for preadolescent children the intervention was effective in decreasing depressive symptoms and behavioural problems.\n This study is the first to show a beneficial effect of a single-session early psychological intervention after RTA in preadolescent children. Therefore, an age-specific approach in an early stage after RTAs may be a promising way for further research. Younger children can benefit from the intervention evaluated here. However, these results have to be interpreted with caution, because of small subgroup sizes. Future studies are needed to examine specific approaches for children and adolescents. Also, the intervention evaluated here needs to be studied in other groups of traumatised children.\n Clinical Trial Registry: ClinicalTrials.gov: NCT00296842.", "Acute stress disorder (ASD) is a precursor of chronic posttraumatic stress disorder (PTSD). Twenty-four participants with ASD following civilian trauma were given 5 sessions of either cognitive-behavioral therapy (CBT) or supportive counseling (SC) within 2 weeks of their trauma. Fewer participants in CBT (8%) than in SC (83%) met criteria for PTSD at posttreatment. There were also fewer cases of PTSD in the CBT condition (17%) than in the SC condition (67%) 6 months posttrauma. There were greater statistically and clinically significant reductions in intrusive, avoidance, and depressive symptomatology among the CBT participants than among the SC participants. This study represents the 1st demonstration of successful treatment of ASD with CBT and its efficacy in preventing chronic PTSD.", "Acute stress disorder permits early identification of trauma survivors who are at risk of developing chronic posttraumatic stress disorder (PTSD). This study aimed to prevent PTSD in people who developed acute stress disorder after a mild brain injury by early provision of cognitive behavior therapy.\n Twenty-four civilian trauma survivors with acute stress disorder were given five individually administered sessions of either cognitive behavior therapy or supportive counseling within 2 weeks of their trauma.\n Fewer patients receiving cognitive behavior therapy than supportive counseling met criteria for PTSD at a posttreatment evaluation (8% versus 58%, respectively). There were also fewer cases of PTSD at a 6-month follow-up evaluation among those receiving cognitive behavior therapy (17%) than among those receiving supportive counseling (58%). Patients in the cognitive behavior therapy condition displayed less reexperiencing and avoidance symptoms at the follow-up evaluation than patients receiving supportive counseling.\n These findings suggest that PTSD following mild brain injury can be effectively prevented with early provision of cognitive behavior therapy.", "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.", "A large-scale study of the effectiveness of psychotherapeutic methods for the treatment of posttraumatic stress disorders was conducted. The sample consisted of 112 persons suffering from serious disorders resulting from traumatic events (bereavement, acts of violence, and traffic accidents) that had taken place not more than 5 years before. Trauma desensitization, hypnotherapy, and psychodynamic therapy were tested for their effectiveness in comparison with a waiting-list control group. The results indicated that treated cases were significantly lower in trauma-related symptoms than the control group." ]

[ "21059594", "7113926", "2392973", "14501543", "10665215", "1165499", "10772609", "9800180", "17228988" ]

[ "Use of historical data and a novel metric in the evaluation of the effectiveness of hearing conservation program components.", "Efficacy of enforcement in an industrial hearing conservation program.", "Hearing conservation programs (HCPs): the effectiveness of one company's HCP in a 12-hr work shift environment.", "Effectiveness of a tailored intervention to increase factory workers' use of hearing protection.", "Effectiveness of an intervention to increase construction workers' use of hearing protection.", "The effectiveness of hearing protective devices.", "Use of comparison populations for evaluating the effectiveness of hearing loss prevention programs.", "A hearing conservation program for Wisconsin youth working in agriculture.", "Efficacy of a computer-based hearing test and tailored hearing protection intervention." ]

[ "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.", "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.", "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.", "In the United States it is estimated that more than 30 million workers are exposed to harmful levels of noise on the job. When engineering or administrative controls cannot be used to reduce noise, workers should always use hearing protection devices (HPDs) when exposed to loud noise to prevent noise-induced hearing loss (NIHL). Previous research has shown that workers do not always use HPDs when required; therefore, it is essential that workers assume personal responsibility for preventing NIHL by increasing their use of HPDs.\n This study tested the effectiveness of an individually tailored multimedia intervention to increase use of HPDs by factory workers.\n A randomized controlled design was used to compare the effects of a tailored intervention (n= 446) with two other interventions (a nontailored predictor-based intervention (n= 447) and a control intervention (n= 432)) on workers' self-reported use of HPDs 6 to 18 months following the intervention.\n Only those workers receiving the tailored intervention significantly increased their use of HPDs from pretest to posttest. However, this increase significantly differed from the nontailored group but not from the control group.\n Individually-tailored interventions offer promise for changing behavior. In light of the similarity between the results for the tailored intervention and the control intervention groups, further research is needed to understand barriers to HPD use and how to maximize the benefits of individually tailored interventions in this setting.", "In this project we tested the effectiveness of a theory-based intervention (video, pamphlets, and guided practice session) to increase the use of hearing protection devices (HPDs) among Midwestern construction workers and a national group of plumber/pipefitter trainers. Posttest measures were collected 10-12 months following this intervention. Pender's Health Promotion Model (1987) provided the conceptual basis for development of the training program. A total of 837 high-noise-exposed workers were included in the analysis: 652 regional Midwestern construction workers and 185 national plumber/pipefitter trainers. Effectiveness of the intervention was determined through the sequence of analyses recommended by Braver and Braver (1988) for the Solomon Four-Group Design. Analysis of variance and covariance of postintervention use and intention to use HPDs and a meta-analytic test were done. These analyses indicated that the intervention significantly increased use of HPDs but had no effect on intention to use HPDs in the future. Pretesting had no effect on use. Actual or potential applications of this research include guidance in the development of successful theory-based interventions to increase use of HPDs.", "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.", "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.", "Adolescents working in agricultural settings may be exposed to noise levels that result in hearing loss. The article describes the design, implementation, and results of a four-year, hearing conservation program (HCP) conducted at school. Thirty-four schools (753 students) were randomly assigned to either an intervention or control group. The intervention included multicomponent educational strategies and employed features of an industrial HCP. Final compliance surveys indicated 87.5% of intervention students reported using hearing protection devices (HPD) at least some of the time, compared to 45% of control students. The HCP components with the greatest reported influence were distribution of HPDs for use on the farm and yearly hearing tests. Eighty percent of intervention students reported intention to use HPDs in the future. It is feasible to conduct a hearing conservation program with junior high school and senior high school students, and it appears possible to persuade teen-agers to protect themselves from exposure to loud noise while working on a farm.", "Advances in computer technology and accessibility enable researchers to provide individually tailored interventions for behavioral change. Using multimedia technology, this study developed and tested a computer-based hearing test and a tailored intervention. The purpose of this study was to evaluate, using a randomized experimental design, the efficacy of the intervention to increase workers' use of hearing protection. The tailored intervention developed by the research team showed more significant short-term effect measured immediately after the intervention than the control intervention. For the long-term effect measured 1 year after the intervention, both tailored and control groups showed significant increase in their reported use (7% vs. 6%) from preintervention to postintervention, but no significant difference between the two groups. The change accomplished in this study was small progress toward the desired level of 100% use of hearing protection to prevent noise-induced hearing loss. This finding showed that changing workers' hearing protection behavior is difficult." ]

[ "16818273", "16352812", "17233848", "12064916", "16352815", "16798652", "14767084", "12670352", "9003855" ]

[ "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.", "A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia.", "A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease.", "Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial.", "Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis.", "A randomized controlled study evaluating the safety and efficacy of deferiprone treatment in thalassemia major patients from Hong Kong.", "Comparative efficacy of desferrioxamine, deferiprone and in combination on iron chelation in thalassemic children.", "Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassaemia patients.", "Evaluation of a new method of administration of the iron chelating agent deferoxamine." ]

[ "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.", "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.", "Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11.4%) and deferoxamine (11.1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.", "Deferiprone has been suggested as an effective oral chelation therapy for thalassemia major. To assess its clinical efficacy, we compared deferiprone with deferoxamine in a large multicenter randomized clinical trial. One-hundred forty-four consecutive patients with thalassemia major and serum ferritin between 1500 and 3000 ng/ml were randomly assigned to deferiprone (75 mg/kg/day) (n = 71) or deferoxamine (50 mg/kg/day) (n = 73) for 1 year. The main measure of efficacy was the reduction of serum ferritin. Liver and heart iron contents were assessed by magnetic resonance. Liver iron content and fibrosis stage variations were assessed on liver biopsy by the Ishak score in all patients willing to undergo liver biopsy before and after treatment. The mean serum ferritin reduction was 222 +/- 783 ng/ml in the deferiprone and 232 +/- 619 ng/ml in the deferoxamine group (P = 0.81). No difference in the reduction of liver and heart iron content was found by magnetic resonance between the two groups. Thirty-six patients accepted to undergo repeat liver biopsy: 21 in the deferiprone and 15 in the deferoxamine group. Their mean reduction of liver iron content was 1022 +/- 3511 microg/g of dry liver and 350 +/- 524, respectively (P = 0.4). No difference in variation of the Ishak fibrosis stage was observed between the two groups. Treatment was discontinued because of reversible side effects in 5 patients in the deferiprone group (3 hypertransamin/asemia and 2 leukocytopenia) and in none in the deferoxamine group. These findings suggest that deferiprone may be as effective as deferoxamine in the treatment of thalassemia major with few mild and reversible side effects.", "Most deaths in beta-thalassemia major result from cardiac complications due to iron overload. Differential effects on myocardial siderosis may exist between different chelators. A randomized controlled trial was performed in 61 patients previously maintained on subcutaneous deferoxamine. The primary end point was the change in myocardial siderosis (myocardial T2(*)) over 1 year in patients maintained on subcutaneous deferoxamine or those switched to oral deferiprone monotherapy. The dose of deferiprone was 92 mg/kg/d and deferoxamine was 43 mg/kg for 5.7 d/wk. Compliance was 94% +/- 5.3% and 93% +/- 9.7% (P = .81), respectively. The improvement in myocardial T2(*) was significantly greater for deferiprone than deferoxamine (27% vs 13%; P = .023). Left ventricular ejection fraction increased significantly more in the deferiprone-treated group (3.1% vs 0.3% absolute units; P = .003). The changes in liver iron level (-0.93 mg/g dry weight vs -1.54 mg/g dry weight; P = .40) and serum ferritin level (-181 microg/L vs -466 microg/L; P = .16), respectively, were not significantly different between groups. The most frequent adverse events were transient gastrointestinal symptoms for deferiprone-treated patients and local reactions at the infusion site for deferoxamine. There were no episodes of agranulocytosis. Deferiprone monotherapy was significantly more effective than deferoxamine over 1 year in improving asymptomatic myocardial siderosis in beta-thalassemia major.", "A controlled, open-label and randomized study was conducted to evaluate the safety and efficacy of the oral iron chelator deferiprone (L1) in thalassemia major patients from Hong Kong. Forty-nine patients were recruited in total (median age: 20 years; range: 8 to 40 years). The division of the patients was determined based on liver iron content and put into either the poorly-chelated (Group I) or well-chelated (Group II) groups. In Group I, 20 patients received combined therapy of L1 daily plus desferrioxamine (DFO), in a reduced frequency of twice weekly, while the control group consisted of 16 patients who were treated with DFO alone. In Group II, six patients received L1 only, while the control group consisted of seven patients treated with DFO alone. Only patients who participated for longer than 6 months were analyzed for efficacy (n = 44). The median study period was 18 months. Transient and mild gastrointestinal upset (31%), joint pain (15%) and liver enzyme elevation (23%) were the most common side effects noted for L1. No case of neutropenia was observed in this study. Serum ferritin (SF) levels showed significant decline in the poorly-chelated patients using combined therapy (L1 and reduced frequency DFO) as compared to those on DFO alone. However, their pre- and post-study liver iron content was not significantly different. Evaluation of the well-chelated group demonstrated no significant change in SF or liver iron content in both the study and control arms. We conclude that the short-term use of L1, with or without DFO, was safe and efficacious in our Chinese patient cohort. The long-term efficacy of reducing iron overload by treatment regimens including L1 requires further study.", "Ascertainment of an appropriate strategy of iron chelation for multi-transfused thalassemic children in developing countries.\n Prospective study from May 2000 to April 2001.\n Urban tertiary care center.\n Thirty thalassemic children having received more than 20 blood transfusions and a serum ferritin greater than 1500 ng/ml were enrolled and randomized into three groups. Group I received desferrioxamine (DFX) at a dose of 40 mg/kg subcutaneously, 5 days/week. Children in group II received oral deferiprone (L1) at a dose of 75 mg/kg/day daily and group III received a combination of daily L1 at a dose of 75 mg/kg/day and DFX at a dose of 40 mg/kg/day two times per week. The assessment of chelation was done by 24-hr urinary iron excretion (UIE) and measurement of serum ferritin levels at start and after 6 months of follow up. Statistical difference of serum ferritin levels between the three groups was assessed by applying analysis of variance. Analysis of covariance was applied to find out the urinary iron excretion keeping serum ferritin values same in each groups.\n Ferritin levels after 6 months of intervention were maximally decreased in group I. There was a significant difference between groups I and II however, no difference was noted between groups I and group III. There was no statistically significant difference in mean urinary iron excretion by keeping the initial serum ferritin levels equal though it was found to be more in group III as compared to other groups.\n DFX is the most effective chelating drug in iron overloaded multi-transfused thalassemic patients. In view of cost and unacceptability of daily DFX injections, combination therapy is an effective method of chelation thus increasing the compliance and cost effectiveness. Deferiprone (L1) alone is not an effective mode of chelation when used for a short period.", "Desferrioxamine (DFX) alone (40-50 mg/kg/d s.c. over 8-12 h, five times weekly) was compared with combined DFX twice weekly and deferiprone (75 mg/kg/d) over 12 months in previously poorly chelated thalassaemia patients. Serum ferritin fell from 5506 +/- 635 microg/l (mean +/- SEM) to 3998 +/- 604 microg/l (P < 0.001; n = 14) in the DFX group and from 4153 +/- 517 microg/l to 2805 +/- 327 microg/l in the combined group (P < 0.01; n = 11). Deferiprone plus DFX produced a greater mean urine iron excretion (1.01 mg/kg/24 h) than iron intake from blood transfusion in each patient. Main side-effects were skin reactions (DFX alone), nausea and arthralgia (combined therapy). As chelation therapy, the combined protocol was as effective as DFX five times weekly.", "We compared the effectiveness of deferoxamine administered by twice-daily subcutaneous injections with conventional administration by prolonged subcutaneous infusion in 20 patients with thalassemia. Urinary iron excretion was comparable with the two methods but decreased significantly when the total daily dose was administered as a single injection. Local reactions were similar with infusion and injection. Subcutaneous injections of deferoxamine may be considered as an alternative to conventional infusions." ]

[ "10696421", "12971668", "15527158", "12631309", "11247549", "15117299", "9802271", "15868015", "16546538" ]

[ "Randomized controlled trial of directly observed treatment (DOT) for patients with pulmonary tuberculosis in Thailand.", "A randomised controlled clinical trial of the efficacy of family-based direct observation of anti-tuberculosis treatment in an urban, developed-country setting.", "Effectiveness of community-based directly observed treatment for tuberculosis in an urban setting in Tanzania: a randomised controlled trial.", "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 the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan.", "Direct observation of treatment for tuberculosis: a randomized controlled trial of community health workers versus family members.", "Randomised controlled trial of self-supervised and directly observed treatment of tuberculosis.", "Staff training and ambulatory tuberculosis treatment outcomes: a cluster randomized controlled trial in South Africa.", "Family-member DOTS and community DOTS for tuberculosis control in Nepal: cluster-randomised controlled trial." ]

[ "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.", "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.", "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.", "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.", "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.", "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.", "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.", "To assess whether adding a training intervention for clinic staff to the usual DOTS strategy (the internationally recommended control strategy for tuberculosis (TB)) would affect the outcomes of TB treatment in primary care clinics with treatment success rates below 70%.\n A cluster randomized controlled trial was conducted from July 1996 to July 2000 in nurse-managed ambulatory primary care clinics in Cape Town, South Africa. Clinics with successful TB treatment completion rates of less than 70% and annual adult pulmonary TB loads of more than 40 patients per year were randomly assigned to either the intervention (n = 12) or control (n = 12) groups. All clinics completed follow-up. Treatment outcomes were measured in cohorts of adult, pulmonary TB patients before the intervention (n = 1200) and 9 months following the training (n = 1177). The intervention comprised an 18-hour experiential, participatory in-service training programme for clinic staff delivered by nurse facilitators and focusing on patient centredness, critical reflection on practice, and quality improvement. The main outcome measure was successful treatment, defined as patients who were cured and those who had completed tuberculosis treatment.\n The estimated effect of the intervention was an increase in successful treatment rates of 4.8% (95% confidence interval (CI): -5.5% to 15.2%) and in bacteriological cure rates of 10.4% (CI: -1.2% to 22%). A treatment effect of 10% was envisaged, based on the views of policy-makers on the minimum effect size for large-scale implementation.\n This is the first evidence from a randomized controlled trial on the effects of experiential, participatory training on TB outcomes in primary care facilities in a developing country. Such training did not appear to improve TB outcomes. However, the results were inconclusive and further studies are required.", "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." ]

[ "2197001", "8818089", "1567037", "8431336", "2321772", "7702152", "8279255", "7476741", "1997058" ]

[ "Clear fluids three hours before surgery do not affect the gastric fluid contents of children.", "[Possibility of rice porridge for preoperative feeding in children].", "Shortened preanesthetic fasting interval in pediatric cardiac surgical patients.", "Preoperative drinking does not affect gastric contents.", "Ingestion of liquids compared with preoperative fasting in pediatric outpatients.", "The effect of pre-operative oral fluids on morbidity following anaesthesia for minor surgery.", "Effects of 2-, 4- and 12-hour fasting intervals on preoperative gastric fluid pH and volume, and plasma glucose and lipid homeostasis in children.", "Effect of preoperative oral fluids on gastric volume and pH in postpartum patients.", "Ingestion of clear fluids is safe for adolescents up to 3 h before anaesthesia." ]

[ "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 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)", "We have compared the effect of allowing free clear fluids until the time of oral premedication with conventional preoperative fasting. In a prospective, randomized trial, the residual volume and pH of gastric contents after induction of anaesthesia were measured in 100 elective surgical patients allocated randomly to a group in whom the intake of free clear fluids up to the time of premedication was measured (mean 388 ml in 6 h before surgery) or a control group who were fasted for 6 h. Preoperative drinking did not affect either mean (SD) residual gastric volume (22 (21) ml in the study group vs 19 (16) ml in the control group) or pH (study group 2.64 (1.57) vs control group 2.26 (1.45)). The study group experienced less preoperative thirst. Problems with aspiration or regurgitation were not encountered. We believe that allowing elective surgical patients to drink clear fluids until 2 h before anaesthesia may enhance patient comfort without compromising safety.", "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)", "Postoperative morbidity and serum osmolality were studied in 46 patients who were encouraged to drink water until 3 h pre-operatively and 49 receiving the normal fasting regimen prior to minor surgery. There was significantly less thirst in the postoperative period in those patients allowed to drink and subjectively better recovery than after previous anaesthesia. There was no morbidity from ingestion of up to 11 of water 2.5 h pre-operatively. Although there was only a moderate improvement in postoperative recovery we feel that allowing patients to drink water pre-operatively improves patient comfort, especially since patients may have to fast for much longer than guidelines recommend, simply because of the traditional organisation of operating lists.", "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 effect of preoperative oral fluids to postpartum patients on the gastric volume and pH was compared with normally fasting postpartum and non-pregnant patients undergoing sterilisation. Forty consecutive postpartum patients and twenty non-pregnant patients scheduled for sterilisation procedure were selected for the study. All patients were fasted overnight. Twenty postpartum patients were randomly allocated to receive 150 ml of plain water two and half hours before surgery (Group 1), while the remaining postpartum patients (Group 2) and non-pregnant patients (Group 3) continued their overnight fast as usual. After induction of anesthesia, gastric volume and pH was measured in all the patients. The mean gastric volume was found to be 21.9 +/- 8.49 ml in Group 1, 22.55 +/- 8.30 ml in Group 2 and 22.65 +/- 8.17 ml in Group 3. The mean pH was found to be 2.21 +/- 0.98 in Group 1, 2.18 +/- 0.88 in Group 2 and 2.12 +/- 1.02 in Group 3. The difference in the volume and pH in all the three groups was statistically insignificant. The difference in the incidence of patients with combined high risk factors of acid aspiration syndrome (gastric fluid volume > 25 ml and pH < 2.5) among the three groups was also insignificant. The authors conclude that ingestion of 150 ml of plain water approximately two and half hours before scheduled time of surgery in overnight fasted postpartum patients does not increase the risk of aspiration syndrome.", "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." ]

[ "20947097", "12042546", "19057612", "8545223", "16188812", "2000278", "2117205", "3540835", "2405141" ]

[ "Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome.", "A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome.", "Treatment of MAS with PPHN using combined therapy: SLL, bolus surfactant and iNO.", "Surfactant replacement therapy for meconium aspiration syndrome.", "Treatment of severe meconium aspiration syndrome with porcine surfactant: a multicentre, randomized, controlled trial.", "Bovine surfactant replacement therapy in neonates of less than 30 weeks' gestation: a randomized controlled trial of prophylaxis versus treatment.", "A multicenter randomized controlled clinical trial of bovine surfactant for prevention of respiratory distress syndrome.", "Randomized controlled trial of exogenous surfactant for the treatment of hyaline membrane disease.", "A controlled trial of human surfactant replacement therapy for severe respiratory distress syndrome in very low birth weight infants." ]

[ "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.", "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.", "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.", "The pathophysiology of meconium aspiration syndrome (MAS) is related not only to mechanical obstruction of the airways and chemical injury to the respiratory epithelium but also to surfactant inactivation by meconium. A randomized, controlled study was performed to determine whether high-dose surfactant therapy improves the pulmonary morbidity of term infants ventilated for MAS.\n Forty term infants receiving mechanical ventilation for MAS were enrolled in this trial, in which the infants in the study group (n = 20) received up to four doses of 150 mg (6 mL)/kg beractant (Survanta), instilled every 6 hours by continuous infusion for 20 minutes via a side hole endotracheal tube adapter, and the infants in the control group (n = 20) received 6 mL/kg air placebo.\n Mean arterial-to-alveolar PO2 ratio values increased from 0.09 to 0.11 at 1 and 6 hours with a concomitant slight decrease in oxygenation index values from 23.7 to 19.7 at 1 hour and 20.7 at 6 hours after the first dose of surfactant. Oxygenation improved cumulatively after the second and third dose of surfactant, with mean arterial-to-alveolar PO2 ratios and oxygenation indices of 0.18 and 12.1 at 6 hours after the second dose of surfactant and 0.31 and 5.9 at 6 hours after the third dose of surfactant, eliminating the need for a fourth dose in any infant in the study group. After three doses of surfactant, persistent pulmonary hypertension had resolved in all but one of the infants in the study group versus none of the infants in the control group. No air leaks developed in any of the 20 infants in the study group after surfactant therapy, and only 1 infant required extracorporeal membrane oxygenation. Air leaks developed in 5 of the 20 infants in the control group, and 6 underwent extracorporeal membrane oxygenation. The duration of mechanical ventilation, oxygen therapy, and admission was significantly shorter in the surfactant group than in the control group.\n Surfactant replacement therapy, if started within 6 hours after birth, improves oxygenation and reduces the incidence of air leaks, severity of pulmonary morbidity, and hospitalization time of term infants with MAS.", "A randomized, controlled clinical trial was performed in 19 Chinese neonatal intensive care units to evaluate the safety and efficacy of exogenous surfactant replacement therapy for severe meconium aspiration syndrome (MAS) in term and near-term neonates.\n Sixty-one term infants with severe MAS were randomly assigned to either a surfactant or a control group within 36 h after birth. The infants in the surfactant group (n=31) received an initial dose of porcine lung-derived surfactant (Curosurf) at 200 mg/kg, and repeated doses of 200, 100 and 100 mg/kg were given at 6-12 h intervals to a maximum of four doses if oxygenation index (OI) deteriorated by >2 from baseline. The primary outcomes were a reduction of OI to less than 10 and an increase of the pre-treatment a/A PO(2) ratio of 100% over baseline 24 h after surfactant treatment. The secondary outcomes were duration of mechanical ventilation, incidence of complications and survival to discharge from hospital.\n The general demographic characteristics of the study subjects were similar. There was a trend for surfactant-treated infants to have an improvement in arterial oxygenation compared to the control group. In comparison with the control group at 24 h, the surfactant group had a lower mean OI (8.1 vs 10.9), more infants with a 100% increase of a/A PO(2) (83% vs 48%, p<0.01) over baseline, and a larger area under the curve for PaO(2)/FiO(2) over baseline (3762+/-1877 vs 2715+/-1644 mmHg(.)h, p<0.05). Repeated measures of these parameters were also in favour of the surfactant group during 24 h to 3 and 7 d compared to the baseline (p<0.05). No differences were found in mean duration of mechanical ventilation, incidence of major complications and number of survivors between the two groups.\n Surfactant replacement therapy improved oxygenation in the study subjects, suggesting that surfactant may have a role in the treatment of severe MAS in term and near-term infants.", "The influence of the timing of surfactant replacement therapy for the treatment of neonatal respiratory distress syndrome was evaluated in a study of 182 neonates of less than 30 weeks' gestation who were randomly assigned prior to delivery to one of three study groups: control (dummy instillation of air given at birth), early surfactant (surfactant given at birth), or late surfactant (surfactant given at less than 6 hours of age). Subjects in the late surfactant group could avoid treatment if they had a clear chest roentgenogram and required no supplemental oxygen at a mean airway pressure of less than 7 cm of water. All treated neonates were eligible to receive up to three additional doses during the first 5 days of life. The three groups were comparable with respect to birth weight, gestational age, and other perinatal parameters with the exception of a lower cord arterial pH and 1-minute Apgar score in the early surfactant group. Of the 60 neonates randomly assigned to late treatment, 29 (48%) were deemed surfactant sufficient and thereby avoided treatment; the other 31 received their first dose at a mean age of 2.9 hours. There was a significant improvement in gas exchange during the first week of life in both surfactant groups compared with the control group, reflected by differences in fraction of inspired oxygen, arterial/alveolar PO2, and ventilation index (peak pressure x rate on the ventilator) (P less than .001). Surfactant therapy also resulted in a lower incidence of pulmonary air leak and severe chronic lung disease (defined as requirement for respiratory support beyond 36 weeks post-conceptional age). There were no differences between early and late surfactant groups in any of these parameters. The only statistically significant difference between the surfactant groups was that the early group had a higher incidence of mild chronic lung disease (respiratory support beyond 28 days of age) than the late treatment group (P less than .005). Neonates in the late treatment group were extubated earlier and had a shorter neonatal intensive care unit stay than control neonates (P less than .05), whereas those in the early group were not significantly different from control neonates in these parameters. It is concluded that replacement therapy with bovine lung surfactant extract in neonates of less than 30 weeks' gestation results in decreased oxygen and ventilatory requirements during the first week of life and a lower incidence of pulmonary air leak and severe chronic lung disease.(ABSTRACT TRUNCATED AT 400 WORDS)", "Treatment with bovine surfactant (SF-RI 1) was shown to be efficacious in improving pulmonary function and in increasing survival rate without BPD in very premature infants. Surfactant therapy did not affect the risk of major complications of prematurity.", "We conducted a prospective, randomized, unblinded, controlled trial of exogenous bovine surfactant (surfactant TA) in premature infants requiring ventilator support for the treatment of severe hyaline membrane disease. Forty-one low birth weight infants with severe hyaline membrane disease were randomly assigned to saline or surfactant therapy and treated within eight hours of birth. Significant improvements in oxygenation (increased arterial/alveolar PO2) and respiratory support (decreased mean airway pressure) were seen in the group receiving surfactant within four hours after treatment. These improvements were maintained in the surfactant-treated infants, who also had fewer pneumothoraces and fewer number of days in environments of fractional inspiratory oxygen greater than 0.4 mm Hg. No problems were associated with administration of surfactant, and no acute side effects were detected. We conclude that exogenous surfactant, administered early in the course of severe hyaline membrane disease, is an effective therapy that can diminish the amount of respiratory support required during the first 48 hours of life.", "In a randomized, controlled study, human surfactant derived from amniotic fluid was administered within 12 hours of birth to infants with severe respiratory distress syndrome who were born at 24 to 32 weeks of gestation weighing less than or equal to 1500 gm. A second dose of surfactant was given to patients in the treatment group if they met ventilator requirements indicating relapse or lack of response to the initial dose. No significant improvement was observed in mortality rate (9/28 vs 15/31) or incidence of bronchopulmonary dysplasia (5/28 vs 3/31) when surfactant-treated infants were compared with control subjects, although there was a significant reduction in initial respirator and inspired oxygen requirements and the arterial/alveolar oxygen ratio improved. In addition, there was a significant reduction in pulmonary air leak in treated infants (10/28 vs 20/31; p less than 0.05). Retreatment was associated with an attenuated ventilatory response and with a higher mortality rate (7/14) than that of infants who did not require a second dose (2/14; p = 0.05), indicating a more severe form of disease. Multiple discriminant analysis, including eight independent variables, revealed that increasing birth weight, earlier age at surfactant treatment, and female gender were significantly associated with survival. These data suggest that early surfactant treatment may reduce mortality rates in very low birth weight infants with severe respiratory distress syndrome, as well as reduce ventilator requirements and the incidence of pulmonary air leaks." ]

[ "15118469", "19298950", "18041238", "18500080", "15522364", "14709300", "9052620", "11087152", "21573091" ]

[ "A prospective, comparative study between endoscopic cyclophotocoagulation and the Ahmed drainage implant in refractory glaucoma.", "Corneal wavefront errors 24 months after deep lamellar endothelial keratoplasty and penetrating keratoplasty.", "Randomized prospective comparison of visian toric implantable collamer lens and conventional photorefractive keratectomy for moderate to high myopic astigmatism.", "Photorefractive keratectomy with mitomycin C versus LASIK in custom surgeries for myopia: a bilateral prospective randomized clinical trial.", "Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings: SST report no. 13.", "Treatment of acute pseudophakic cystoid macular edema: Diclofenac versus ketorolac.", "5-fluorouracil in combined trabeculectomy and clear-cornea phacoemulsification with posterior chamber intraocular lens implantation. A one-year randomized, controlled clinical trial.", "Double-blind comparison of two corticosteroid regimens plus mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection.", "A prospective, contralateral comparison of photorefractive keratectomy (PRK) versus thin-flap LASIK: assessment of visual function." ]

[ "To compare endoscopic cyclophotocoagulation (ECP) and the Ahmed drainage implant in the treatment of refractory glaucoma.\n Sixty-eight eyes of 68 patients with refractory glaucoma were prospectively assigned to either ECP or Ahmed tube shunt implantation. All procedures were performed by a single surgeon. Eyes that were included were pseudophakic with a history of at least one trabeculectomy with antimetabolite, an intraocular pressure (IOP) equal to or above 35 mm Hg on maximum tolerated medical therapy, and a visual acuity better than light perception. Exclusion criteria included eyes that had had previous glaucoma drainage device implantation or a cyclodestructive procedure. Success was defined as an IOP more than 6 mm Hg and less than 21 mm Hg, with or without topical anti-hypertensive therapy.\n The mean follow-up was 19.82 +/- 8.35 months and 21.29 +/- 6.42 months, for the Ahmed and ECP groups, respectively (P = 0.4). The preoperative IOP, 41.32 +/- 3.03 mm Hg (Ahmed) and 41.61 +/- 3.42 mm Hg (ECP) (P = 0.5), and the mean postoperative IOP, at 24 months follow-up, 14.73 +/- 6.44 mm Hg (Ahmed) and 14.07 +/- 7.21 mm Hg (ECP) (P = 0.7), were significantly different from baseline in both groups (P < 0.001). Kaplan-Meier survival curve analysis showed a probability of success at 24 months of 70.59% and 73.53% for the Ahmed and ECP groups, respectively (P = 0.7). Complications included choroidal detachment (Ahmed 17.64%, ECP 2.94%), shallow anterior chamber (Ahmed 17.64%, ECP 0.0%), and hyphema (Ahmed 14.7%, ECP 17.64%).\n There was no difference in the success rate between the Ahmed Glaucoma Valve and ECP in refractory glaucoma. The eyes that underwent Ahmed tube shunt implantation had more complications than those treated with ECP.", "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.", "To compare the Visian Toric Implantable Collamer Lens (TICL), a toric phakic intraocular lens (IOL), and photorefractive keratectomy (PRK) in the correction of moderate to high myopic astigmatism.\n This prospective, randomized study consisted of 43 eyes implanted with the TICL (20 bilateral cases) and 45 eyes receiving PRK with mitomycin C (22 bilateral cases) with moderate to high myopia (-6.00 to -20.00 diopters [D] sphere) measured at the spectacle plane and 1.00 to 4.00 D of astigmatism. All patient treatment and follow-up occurred at the Naval Medical Center San Diego. Study follow-up was 1 day, 1 week, 1, 3, 6, and 12 months postoperative.\n Mean best spectacle-corrected visual acuity (BSCVA), change in BSCVA, proportion of cases with improvement of 1 or more lines of BSCVA, proportion of cases with BSCVA and uncorrected visual acuity (UCVA) 20/12.5 or better, proportion of cases with BSCVA and UCVA 20/16 or better (6 months, 88% vs 54%, P=.002), and predictability +/-1.00 D (6 months, 100% vs 67%, P<.001) were all significantly better in the TICL group than the PRK group at all time periods studied postoperatively. Similarly, contrast sensitivity, tested at both the 5% photopic level and the 25% mesopic level, was significantly better at all postoperative time points in the TICL group. Mean spherical equivalent refraction was closer to emmetropia (0.28+/-0.41 vs 0.76+/-0.86, P=.005), and predictability +/-0.50 D and stability of manifest refraction (+/-0.50 D and +/-1.00 D) were significantly better in the TICL group at all postoperative visits through 6 months. Mean astigmatism correction at 6 months was not significantly different between the two groups (0.52+/-0.33 vs 0.46+/-0.35, P=.450).\n The TICL performed better than PRK in all measures of safety (BSCVA), efficacy (UCVA), predictability, and stability in this comparison, supporting the TICL as a viable alternative to existing refractive surgical treatments.", "To compare photorefractive keratectomy (PRK) with prophylactic use of mitomycin C (MMC) and LASIK in custom surgeries for myopic astigmatism.\n Eighty-eight eyes of 44 patients with a minimum estimated ablation depth of 50 microm were randomized to receive PRK with MMC 0.002% for 1 minute in one eye and LASIK in the fellow eye. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), cycloplegic refraction, slit-lamp microscopy, contrast sensitivity, specular microscopy, aberrometry, and a subjective questionnaire were evaluated. Forty-two patients completed 6-month follow-up.\n Mean spherical equivalent refraction error before surgery and mean ablation depth were -3.99+/-1.20 diopters (D) and 73.09+/-14.55 microm in LASIK eyes, and -3.85+/-1.12 D and 70.7+/-14.07 microm in PRK with MMC eyes, respectively. Uncorrected visual acuity was significantly better in PRK with MMC eyes 3 months (P=.04) and 6 months (P=.01) after surgery. Best spectacle-corrected visual acuity and spherical equivalent refraction did not differ significantly in the groups during follow-up (P>.05). Significant haze was not observed in any PRK with MMC eye. Mean higher order aberration was lower in PRK with MMC eyes postoperatively compared with LASIK eyes (P=.01). Better contrast sensitivity was observed in PRK with MMC eyes than LASIK eyes (P<.05). The endothelial cell count did not differ significantly between groups (P=.65). In terms of visual satisfaction, PRK with MMC eyes were better rated.\n Photorefractive keratectomy with MMC appears to be more effective than LASIK in custom surgery for moderate myopia. During 6-month follow-up, no toxic effects of MMC were evident. Long-term follow-up is necessary to attest its safety.", "To present best-corrected visual acuity (BCVA) findings and other clinical outcomes from eyes of patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of predominantly hemorrhagic subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration.\n Randomized clinical trial (SST Group B Trial).\n Eligible patients had subfoveal choroidal neovascular lesions greater than 3.5 disk areas (8.9 mm2) composed of at least 50% blood (either blood or CNV underlying the center of the foveal avascular zone) and BCVA of 20/100 to light perception in the study eye.\n Patients were assigned randomly at time of enrollment to observation or surgical removal of blood and any associated CNV.\n A successful outcome was defined a priori as either improvement in visual acuity (VA), no change in VA, or a decline in VA of no more than 1 line (7 letters) from baseline to the 24-month examination based on an intent-to-treat analysis.\n Of 336 patients enrolled, 168 were assigned to each treatment arm; treatment arms were balanced by baseline characteristics. Of 1501 expected examinations 3 months through 36 months after baseline, 1370 (91%) were performed. Loss of > or =2 lines (> or =8 letters) of VA occurred in 56% of surgery eyes, versus 59% of observation eyes examined at 24 months. Although severe loss of VA was not the primary outcome of interest, surgery more often prevented such loss: 36% in the observation arm versus 21% in the surgery arm at the 24-month examination (chi2 P = 0.004). Of initially phakic eyes, the cumulative percentage that had undergone cataract surgery by 24 months was 44% in the surgery arm, compared with 6% in the observation arm. Twenty-seven eyes (16%) in the surgical arm, compared with 3 eyes (2%) in the observation arm, had a rhegmatogenous retinal detachment (RD).\n Submacular surgery as performed in the SST Group B Trial did not increase the chance of stable or improved VA (the primary outcome of interest) and was associated with a high risk of rhegmatogenous RD, but did reduce the risk of severe VA loss in comparison with observation. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.", "To investigate whether topical diclofenac sodium 0.1% solution (Voltaren Ophthalmic) is as efficacious as topical ketorolac tromethamine 0.5% solution (Acular) in the treatment of established, chronic cystoid macular edema (CME) after uneventful phacoemulsification cataract extraction with posterior chamber intraocular lens (IOL) implantation.\n Referral-based vitreoretinal private practice.\n This randomized prospective study comprised 34 consecutive patients with clinical CME after uneventful phacoemulsification cataract extraction with posterior chamber IOL implantation who were referred to a private vitreoretinal practice for evaluation and management. Exclusion criteria included a history of previous intraocular surgery, vitreous loss during cataract surgery, CME, uveitis, and vitreoretinal pathology. The eye with CME was treated with 1 drop 4 times daily of diclofenac sodium 0.1% solution or ketorolac tromethamine 0.5% solution. Outcomes were measured by observing for improvement in CME and visual acuity.\n Both treatment methods resulted in a significant reduction in CME and a significant improvement in visual acuity. Within 26 weeks, diclofenac reduced CME in 16 patients (89%) and ketorolac, in 14 patients (88%) (P =.92, confidence interval [CI] 95%). Within 26 weeks, diclofenac eliminated CME in 14 patients (78%) and ketorolac, in 12 patients (75%) (P =.86, CI 95%). The mean time to initial CME reduction was 7.5 weeks with diclofenac and 8.0 weeks with ketorolac (P =.41, CI 95%). The mean time to CME resolution was 13.6 weeks with diclofenac and 12.8 weeks with ketorolac (P =.49, CI 95%).\n Diclofenac sodium 0.1% solution and ketorolac tromethamine 0.5% topical ophthalmic solution eyedrops were equally effective in reducing the severity and duration of CME after uneventful phacoemulsification with posterior chamber IOL implantation. Either solution may be considered for CME after cataract surgery, especially in patients who may not tolerate corticosteroid treatment.", "To test the effect of postoperative subconjunctival 5-fluorouracil (5-FU) on the pressure outcome in combined procedure (limbus-based trabeculectomy + clear-cornea phacoemulsification).\n Prospective randomized, controlled clinical trial; n = 24 eyes (24 patients) with concurrent open-angle glaucoma and cataract; 12 eyes per treatment group; sample size adjusted for a minimal expected difference in the event rate between the 2 treatment groups = 50%, control rate = 20%; type I error = 0.05; power = 95%. Uncomplicated limbus-based trabeculectomy + uncomplicated clear-cornea phacoemulsification + posterior chamber intraocular lens. The 5-FU group = five subconjunctival injections of 5 mg 5-FU, starting from day 8 after surgery, one injection per week. Control group = no injections. The groups were matched for age, preoperative intraocular pressure (IOP), duration of preoperative antiglaucoma treatment, preoperative pilocarpine and adrenergics, preoperative laser trabeculoplasty, and beta-blockers in the fellow eye. The IOP less than or equal to 15 mmHg without treatment 1 year after surgery (IOP = average of the two highest values measured in the diurnal curve, 8 AM to 6 PM, one reading every 2 hours).\n Each patient completed a 1-year follow-up. Ten of 12 eyes of the 5-FU group showed an IOP less than or equal to 15 mmHg at the end of follow-up versus 1 of 12 eyes in the control group (Fisher's exact test, P = 0.00064). The IOP range was 10 to 17 mmHg in the 5-FU group and 14 to 22 mmHg in the control group.\n Postoperative 5-FU may improve the 1-year success rate of trabeculectomy combined with clear-cornea phacoemulsification.", "Renal transplant recipients experience adverse events attributed to corticosteroid therapy.\n This was a multicenter, randomized, double-blind, 6-month, controlled steroid dose-reduction study in renal transplant recipients with an unblinded 6-month follow-up. In the low/stop arm, corticoste. roids were given at half the dosage of control for 3 months from the date of transplantation, and then withdrawn. Both arms received mycophenolate mofetil and cyclosporine. The primary endpoint was the incidence of biopsy-proven acute rejection at 6 months posttransplantation.\n There were 248 patients in the control group and 252 in the low/stop group. At 6 months the low/stop group had more biopsy-proven acute rejection episodes than the control (23% vs. 14%; P=0.008). At 12 months this increased to 25% vs. 15%. Most rejections were Banff grade I. Twelve-month graft loss was 5% in the low/stop group vs. 4% in the control. At 6 and 12 months serum cholesterol (P<0.01, P<0.01), triglycer. ides (P<0.01, P<0.01), and systolic blood pressure (P<0.001, P<0.001) were lower in the low/stop group. Diastolic pressure was lower (P<0.01) and lumbar spine bone density was greater (P<0.01) in the low/ stop group at 12 months.\n In renal transplant recipients treated with mycophenolate mofetil and cyclosporine, reduction and early withdrawal of the prophylactic corticosteroid dose is feasible without an unacceptable increase in serious rejection episodes. This is accompanied by a significant reduction of steroid-related adverse events.", "To compare differences in visual acuity, contrast sensitivity, complications, and higher-order ocular aberrations (HOAs) in eyes with stable myopia undergoing either photo-refractive keratectomy (PRK) or thin-flap laser in situ keratomileusis (LASIK) (intended flap thickness of 90 μm) using the VISX Star S4 CustomVue excimer laser and the IntraLase FS60 femtosecond laser at 1, 3, and 6 months postoperatively.\n In this prospective, masked, and randomized pilot study, refractive surgery was performed contralaterally on 52 eyes: 26 with PRK and 26 with thin-flap LASIK. Primary outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), contrast sensitivity, and complications.\n At 6 months, mean values for UDVA (logMAR) were -0.043 ± 0.668 and -0.061 ± 0.099 in the PRK and thin-flap LASIK groups, respectively (n = 25, P = 0.466). UDVA of 20/20 or better was achieved in 96% of eyes undergoing PRK and 92% of eyes undergoing thin-flap LASIK, whereas 20/15 vision or better was achieved in 73% of eyes undergoing PRK and 72% of eyes undergoing thin-flap LASIK (P > 0.600). Significant differences were not found between treatment groups in contrast sensitivity (P ≥ 0.156) or CDVA (P = 0.800) at postoperative 6 months. Types of complications differed between groups, notably 35% of eyes in the thin-flap LASIK group experiencing complications, including microstriae and 2 flap tears.\n Under well-controlled surgical conditions, PRK and thin-flap LASIK refractive surgeries achieve similar results in visual acuity, contrast sensitivity, and induction of HOAs, with differences in experienced complications." ]

[ "15379121", "20194844", "15071604", "21231927", "15044693", "12488405", "17374742", "3028596", "1260337" ]

[ "[Preliminary results of a multicenter randomized study on the treatment of acute promyelocytic leukemias].", "Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia.", "Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission--experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG).", "A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia.", "All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia.", "Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer--Austrian Breast and Colorectal Cancer Study Group Trial 5.", "A randomized study with or without intensified maintenance chemotherapy in patients with acute promyelocytic leukemia who have become negative for PML-RARalpha transcript after consolidation therapy: the Japan Adult Leukemia Study Group (JALSG) APL97 study.", "Alternating versus sequential chemotherapy in small cell lung cancer. A randomized German multicenter trial.", "Response and survival in advanced breast cancer after two non-cross-resistant combinations." ]

[ "To study efficacy of maintenance therapy of patients with acute promyelocytic leukemia (APL) in the APL treatment Russian multicenter trial.\n The trial was made with participation of 18 hematological departments of clinics in Russia. A total of 68 APL patients entered the trial. The maintenance therapy consisted of 5-day courses of cytostatic drugs which alternated or did not alternate with 5-day courses of ATRA. Cytogenetic tests were made in 31 patients, t(15;17) was detected in 26 of them. Molecular examination conducted in 28 patients discovered chimeric transcript PML/RARa in 26 of them. Of 20 patients examined in Hematological Research Center, 7 (35%) had a bcr 1/2 variant of the transcript PML/RARa, 13 (65%)--bcr 3 variant.\n 65 patients were eligible for assessment. A complete remission was achieved in 90% cases. No resistance was observed. In follow-up within 30 months the recurrence rate was similar on both treatments. The results of the induction therapy and survival in patients with different variants of the transcripts were also similar. Overall 2.5 year survival for all the patients was 77%, recurrence-free--80%. The survival analysis in patients with leukocytosis higher and lower 10 x 10(9)/l found no statistical differences by the survival. Patients with hyperleukocytosis had higher early lethality than patients with leukocytes under 10 x 10(9)/l (25% vs 5.3%, p = 0.03).\n The APL 06.01 protocol showed high efficacy of the relevant maintenance which provides a complete molecular remission in the majority of patients with probable recurrence-free 2.5 year survival 80%.", "Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized studies in patients with chronic lymphocytic leukemia (CLL). This trial was designed to compare chemoimmunotherapy with chemotherapy alone in patients with previously treated CLL.\n This international, multicenter, randomized trial compared six cycles of rituximab plus fludarabine and cyclophosphamide (R-FC) with six cycles of fludarabine and cyclophosphamide alone (FC) in patients with previously treated CLL. A total of 552 patients with Binet stage A (1%), B (59%), or C (31%) disease entered the study and were randomly assigned to receive R-FC (n = 276) or FC (n = 276).\n After a median follow-up time of 25 months, rituximab significantly improved progression-free survival in patients with previously treated CLL (hazard ratio = 0.65; P < .001; median, 30.6 months for R-FC v 20.6 months for FC). Event-free survival, response rate, complete response rate, duration of response, and time to new CLL treatment or death were also significantly improved. Although the rates of adverse events, grade 3 or 4 events, and serious adverse events were slightly higher in the R-FC arm, R-FC was generally well tolerated, with no new safety findings and no detrimental effect on quality of life.\n R-FC significantly improved the outcome of patients with previously treated CLL.", "Patients with CLL responding to initial chemotherapy with fludarabine alone (F) or in combination with cyclophosphamide (FC) were randomized for treatment with alemtuzumab (30 mg i.v. TIW, 12 weeks) or observation. Of 21 evaluable patients, 11 were randomized to alemtuzumab before the study was stopped due to severe infections in seven of 11 patients. These infections (one life-threatening pulmonary aspergillosis IV; four CMV reactivations III requiring i.v. ganciclovir; one pulmonary tuberculosis III; one herpes zoster III) were successfully treated and not associated with cumulative dose of alemtuzumab. In the observation arm, one herpes zoster infection II and one sinusitis I were documented. At 6 months after randomization, two patients in the alemtuzumab arm converted to CR, while three patients in the observation arm progressed. After alemtuzumab treatment, five of six patients achieved a molecular remission in peripheral blood while all patients in the observation arm remained MRD-positive (P=0.048). At 21.4 months median follow-up, patients receiving alemtuzumab showed a significant longer progression-free survival (no progression vs mean 24.7 months; P=0.036). In conclusion, a consolidation therapy with alemtuzumab is able to achieve molecular remissions and longer survival in CLL, but a safe treatment regimen needs to be determined.", "Combination fludarabine (F), cyclophosphamide (C) and rituximab (R) is the standard front-line therapy in chronic lymphocytic leukaemia (CLL), but appropriate treatment of relapsed/refractory CLL is less clear. Combined FC and mitoxantrone (M) has been reported to be effective in a single arm study, and rituximab when added to chemotherapy in CLL is synergistic. A randomized, two-stage, Phase II trial of FCM and FCM-R was conducted in relapsed CLL. The primary endpoint was response rate 2 months after therapy, assessed according to the 2008 International Workshop CLL criteria. In addition, minimal residual disease (MRD) in the marrow was studied 2 months after therapy, with MRD negativity defined as <0·01% CLL cells. Fifty-two patients were entered, 26 in each arm. The overall response rates to FCM and FCM-R were 58% and 65% respectively. Combined complete response (CR) and CR with incomplete marrow recovery [CR(i)] was 15% (95% confidence interval [CI]:4-35%) for FCM and 42% (95%CI:23-63%) for FCM-R, with eight patients achieving MRD negativity (3 FCM; 5 FCM-R). The toxicity of both regimens was acceptable. In conclusion, the addition of rituximab to FCM improves the response rates in relapsed CLL, resulting in more complete remissions and without additional safety concerns. Efficacy and safety should be fully tested in a randomized Phase III trial.\n © 2011 Blackwell Publishing Ltd.", "Both all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) have proven to be very effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but they had not been used jointly in an integrated treatment protocol for remission induction or maintenance among newly diagnosed APL patients. In this study, 61 newly diagnosed APL subjects were randomized into three treatment groups, namely by ATRA, As(2)O(3), and the combination of the two drugs. CR was determined by hematological analysis, tumor burden was examined with real-time quantitative RT-PCR of the PML-RAR alpha (promyelocytic leukemia-retinoic acid receptor alpha) fusion transcripts, and side effects were evaluated by means of clinical examinations. Mechanisms possibly involved were also investigated with cellular and molecular biology methods. Although CR rates in three groups were all high (> or =90%), the time to achieve CR differed significantly, with that of the combination group being the shortest one. Earlier recovery of platelet count was also found in this group. The disease burden as reflected by fold change of PML-RAR alpha transcripts at CR decreased more significantly in combined therapy as compared with ATRA or As(2)O(3) mono-therapy (P < 0.01). This difference persisted after consolidation (P < 0.05). Importantly, all 20 cases in the combination group remained in CR whereas 7 of 37 cases treated with mono-therapy relapsed (P < 0.05) after a follow-up of 8-30 months (median: 18 months). Synergism of ATRA and As(2)O(3) on apoptosis and degradation of PML-RAR alpha oncoprotein might provide a plausible explanation for superior efficacy of combination therapy in clinic. In conclusion, the ATRA/As(2)O(3) combination for remission/maintenance therapy of APL brings much better results than either of the two drugs used alone in terms of the quality of CR and the status of the disease-free survival.", "Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy.\n Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death.\n With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195).\n Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.", "To examine the efficacy of intensified maintenance chemotherapy, we conducted a prospective multicenter trial in adult patients with newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Of the 302 registered, 283 patients were assessable and 267 (94%) achieved complete remission. Predicted 6-year overall survival in all assessable patients and disease-free survival in patients who achieved complete remission were 83.9% and 68.5%, respectively. A total of 175 patients negative for PML-RARalpha at the end of consolidation were randomly assigned to receive either intensified maintenance chemotherapy (n = 89) or observation (n = 86). Predicted 6-year disease-free survival was 79.8% for the observation group and 63.1% for the chemotherapy group, showing no statistically significant difference between the 2 groups (P = .20). Predicted 6-year survival of patients assigned to the observation was 98.8%, which was significantly higher than 86.2% in those allocated to the intensified maintenance (P = .014). These results indicate that the intensified maintenance chemotherapy did not improve disease-free survival, but rather conferred a significantly poorer chance of survival in acute promyelocytic leukemia patients who have become negative for the PML-RARalpha fusion transcript after 3 courses of intensive consolidation therapy.", "A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow-up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two-year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression-free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life-threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV.", "A prospective study with two cytotoxic combinations (cyclophosphamide, methotrexate, and fluorouracil (CMF), and adriamycin plus vincristine (AV)) was carried out in 110 patients with advanced breast cancer. There was no significant difference between the treatment groups in the response rate after primary treatment, the median duration of response, and the median survival. In both groups responders survived for longer than non-responders. Secondary treatment after crossover for progression or relapse resulted in response rates of 35% for AV and 20% for CMF. Toxicity was mainly represented by reversible haemosuppression. These results are comparable with those obtained with other multiple-drug regimens, and combination chemotherapy alone seems to have reached a plateau in its capacity to control disseminated breast cancer." ]

[ "8348504", "20034729", "9119635", "8692531", "8727805", "1743226", "8709374", "20173364", "15948743" ]

[ "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.", "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.", "Update on the Dutch Cooperative Trial: mitomycin versus bacillus Calmette-Guérin-Tice versus bacillus Calmette-Guérin RIVM in the treatment of patients with pTA-pT1 papillary carcinoma and carcinoma in situ of the urinary bladder. Dutch South East Cooperative Urological Group.", "Intravesical chemotherapy (mitomycin C) versus immunotherapy (bacillus Calmette-Guérin) in superficial bladder cancer.", "A randomized multicenter trial of adjuvant therapy in superficial bladder cancer: transurethral resection only versus transurethral resection plus mitomycin C versus transurethral resection plus bacillus Calmette-Guerin. Participating Clinics.", "Bacillus Calmette-Guérin versus gemcitabine for intravesical therapy in high-risk superficial bladder cancer: a randomised prospective study.", "Twelve-year follow up of a randomized prospective trial comparing bacillus Calmette-Guerin and epirubicin as adjuvant therapy in superficial bladder cancer." ]

[ "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.", "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.", "Prophylactic intravesical treatment with chemotherapeutic agents or one of the different strains of the immunomodulator bacillus Calmette-Guérin (BCG) reduces tumor recurrence and may prevent progression after transurethral resection (TUR) of superficial bladder cancer. Clinical and pathological prognostic factors are used to categorize different groups at risk for disease recurrence and progression. Solitary low-grade (G1, 2A), low-stage (pTa) tumors have less than a 5% risk of progression, while pT1 G3 tumors with concomitant carcinoma in situ (CIS) have a considerably higher risk of progression and metastases. Thus, prospective clinical trials should consider the different risks associated with different prognostic groups and stratify patients accordingly. The Dutch Cooperative Trial evaluated mitomycin versus BCG-Tice versus BCG-RIVM in 469 patients with pTA/pT1 carcinoma and CIS of the urinary bladder after TUR. Of 437 evaluable patients, 50 had CIS, 254 had pTA tumors, and 133 had pT1 tumors. No statistical differences were observed in toxicity between the two strains of BCG, but local and systemic side effects were more frequent in the BCG groups versus the mitomycin group. No differences in response rate were observed between the 3 treatment groups in patients with CIS. A statistically significant difference in favor of mitomycin was seen, however, in patients with papillary tumors. Mitomycin and BCG-RIVM were equally effective, and mitomycin proved significantly more effective than BCG-Tice. No significant difference in efficacy was observed between the two strains of BCG. Disease recurrence during the study in patients with papillary tumors was seen in 43% of mitomycin-treated patients, 64% of the BCG-Tice group, and 46% of patients treated with BCG-Rivm. However, a subgroup analysis for time to first recurrence for pTa versus pT1 and for grade 1 and 2 versus grade 3 papillary tumors showed no statistically significant between-group difference. Further studies comparing identical regimens, doses, and patient groups are needed to define more clearly which patient groups and tumors are more likely to respond to intravesical therapy.", "Both intravesical mitomycin C (MMC) and bacillus Calmette-Guérin (BCG; Pasteur strain F) were effective in the present prospective randomized multicenter study consisting of 91 patients with frequently recurrent superficial (Ta-T1) bladder cancer. The result was in favour of BCG, as shown by the measurements with complete response (CR), disease-free interval and recurrence rate. CR of 58% with MMC and 40% with BCG were reached in 22 instillation series on carcinoma in situ of 18 patients. Due to side effects, MMC instillations were discontinued in 8.6%, and BCG instillations in 19.6%, respectively. After the 2-year follow-up also 1 case of pulmonary tuberculosis occurred in the BCG group.", "A randomized multicenter trial was done to compare transurethral resection only to transurethral resection plus adjuvant mitomycin C and bacillus Calmette Guerin (BCG) instillation for treatment of superficial bladder cancer (stage pTa/1 grades 1 to 3 except primary stage pTa grade 1).\n Included in the study were 337 patients with superficial stage pTa/1 grades 1 to 3 bladder cancer except primary stage pTa grade 1 tumors. One group underwent transurethral resection alone. Mitomycin C (20 mg./50 ml. sodium chloride) was given every 2 weeks during year 1 and once a month during year 2. BCG (120 mg/50 ml. sodium chloride was instilled once a week for 6 weeks and once a month for 4 months.\n At a median followup of 20.2 months, a decrease in recurrence rate was noted for both drug instillations compared to transurethral resection only. The relative risk of recurrence was 0.508 after mitomycin C and 0.618 after BCG instillation compared to transurethral resection alone. There was no significant difference between the mitomycin C and BCG instillations. The progression rate was comparable in all 3 therapy groups, with an estimated common progression rate of 4.22% per year. Side effects occurred most frequently during or after BCG instillation, most often consisting of cystitis. One patient required cystectomy because of ulcerating cystitis and a prostatic abscess subsequent to unsuccessful tuberculostatic therapy. There were no systemic complications.\n Our study showed a positive effect of adjuvant chemotherapy and immunotherapy on decreasing tumor recurrence rate. No influence was observed concerning progression rate, which was low overall.", "To evaluate the safety, tolerability and efficacy of adjuvant intravesical gemcitabine versus bacillus Calmette-Guérin (BCG) in the treatment of high-risk superficial bladder cancer.\n 64 patients with high-risk superficial bladder cancer (pT1 and/or G3 and/or CIS) were assigned to interventions (gemcitabine or BCG) in a randomised controlled trial. All the patients were evaluated for recurrence and progression rates (primary endpoint) and safety and tolerability (secondary endpoint).\n The two groups were comparable in terms of baseline characteristics. Tolerability was better for gemcitabine, whereas the BCG group experienced the need for delayed treatment or withdrawal in 12.5% of cases. At a mean follow-up of 44 months, the recurrence rate in patients treated with BCG was 28.1%; the recurrence rate in patients who received gemcitabine was 53.1% (p = 0.037). Time to recurrence was shorter in patients treated with BCG (25.6 vs. 39.4 months, p = 0.042). No patients developed disease progression.\n Gemcitabine is significantly inferior to BCG, but given its favourable toxicity profile, it may be useful for patients intolerant to or otherwise unable to receive BCG.\n Copyright 2010 S. Karger AG, Basel.", "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." ]

[ "9811084", "18054445", "10519687", "17364418", "11414349", "16150764", "12127464", "9264626", "11932132" ]

[ "Matching alcoholism treatments to client heterogeneity: treatment main effects and matching effects on drinking during treatment. Project MATCH Research Group.", "Brief alcohol intervention for general hospital inpatients: a randomized controlled trial.", "A study of minimal interventions for problem drinkers in acute care settings.", "A cognitive behavioral therapy for alcohol-dependent domestic violence offenders: an integrated substance abuse-domestic violence treatment approach (SADV).", "A randomized controlled trial of motivational enhancement therapy (MET) for mild to moderate alcohol dependence.", "Effectiveness of treatment for alcohol problems: findings of the randomised UK alcohol treatment trial (UKATT).", "A trial of \"standard\" outpatient alcoholism treatment vs. a minimal treatment control.", "[Effectiveness of brief medical counseling to reduce drinkers' alcohol consumption].", "A large randomized placebo controlled study of auricular acupuncture for alcohol dependence." ]

[ "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.", "To test the effectiveness of a brief alcohol intervention among non-dependent general hospital inpatients with alcohol problems, delivered by either a specialized liaison service or hospital physicians.\n All inpatients of 29 wards from four general hospitals of one region in Germany were screened for alcohol problems (n=14,332). Of those screening positive, 595 patients were included in a randomized controlled group design using a time-frame. Patients with alcohol dependence were not considered in this study. Patients received Motivational Interviewing based counselling either by a specialized liaison service, by hospital physicians trained under routine conditions or received hospital treatment as usual without additional counselling. One year later, alcohol consumption, motivation and well-being were assessed. Sample survey analyses and generalized estimating equations were conducted.\n At baseline, the three groups differed regarding motivation, with higher motivation among the controls. At follow-up, the groups did not differ regarding alcohol consumption, alcohol-related problems and well-being. All groups decreased their alcohol consumption significantly. Regarding motivation, longitudinal analyses revealed significant interaction effects of time and intervention (p<0.05), indicating a stronger increase of readiness to change drinking and a less profound drop of readiness to seek help among those who received intervention compared to the controls.\n The intervention was not effective in reducing alcohol consumption or in increasing well-being 12 months after hospitalization. It had a positive effect on readiness to change drinking and on readiness to seek formal help for alcohol problems. The intervention groups compensated their lag of motivation.", "This article reports an investigation of three minimal interventions for potential problem drinkers in general hospital wards. The interventions were: (a) brief advice; (b) the provision of health education literature; (c) a combination of both the advice and literature. One year after recruitment the mean levels of alcohol consumption and the number of alcohol-related problems reported by the cohort was significantly reduced. These reductions were supported by reductions in the mean levels of GGT and AST, but not in mean MCV. No statistically significant treatment effects were found. The results are presented and implications for nursing are discussed.", "This pilot study evaluated the efficacy of a twelve-session cognitive behavioral group therapy for alcohol-dependent males with co-occurring interpersonal violence (IPV). Participants were 85 alcohol-dependent males who were arrested for domestic violence within the past year. Seventy-eight male adults were randomized to either a cognitive behavioral Substance Abuse Domestic Violence (SADV) group (N = 40) or a Twelve-Step Facilitation (TSF) Group (N = 38). There was no significant difference between SADV versus TSF in the number of sessions attended. Regarding substance use, the group assigned to SADV reported using alcohol significantly fewer days (eg, 90 days of abstinence across the 12 weeks of treatment) as compared to the TSF group. Regarding physical violence, there was a trend for participants in the SADV condition to achieve a greater reduction in the frequency of violent episodes across time compared to individuals in the TSF group. These data suggest the promise of the SADV group therapy approach for alcohol-dependent males with a history of IPV who present for substance abuse treatment.", "This study was designed to conduct a randomized controlled trial of motivational enhancement therapy (MET) with two control conditions: nondirective reflective listening (NDRL) and no further counseling (NFC); and to conduct this study in a sample of patients with a primary diagnosis of mild to moderate alcohol dependence, in a \"real-life\" clinical setting.\n Patients with mild to moderate alcohol dependence were recruited, assessed and treated at the Community Alcohol and Drug Service of Christchurch, New Zealand. All patients received a feedback/education session before randomization to either four sessions of MET, four sessions of NDRL, or NFC. Outcome data on 122 subjects (57.4% men) were obtained 6 months following the end of treatment, by an interviewer who was blind to the treatment condition. The primary drinking outcome was unequivocal heavy drinking, defined as drinking 10 or more standard drinks six or more times in the follow-up period. Global assessment scale (GAS) measured general personal/social functioning.\n Of patients treated with MET, 42.9% showed unequivocal heavy drinking compared with 62.5% of the NDRL and 65.0% of the NFC groups (p = .04). No significant differences were found for GAS score according to treatment condition.\n In patients with mild to moderate alcohol dependence, MET is more effective for reducing unequivocal heavy drinking than either a feedback/education session alone or four sessions of NDRL. MET can be considered an effective \"value added\" counseling intervention in a real-life clinical setting. In patients with mild to moderate alcohol dependence, nondirective reflective listening provides no additional advantage over a feedback/education session alone.", "To compare the effectiveness of social behaviour and network therapy, a new treatment for alcohol problems, with that of the proved motivational enhancement therapy.\n Pragmatic randomised trial.\n Seven treatment sites around Birmingham, Cardiff, and Leeds.\n 742 clients with alcohol problems; 689 (93.0%) were interviewed at three months and 617 (83.2%) at 12 months.\n Social behaviour and network therapy and motivational enhancement therapy.\n Changes in alcohol consumption, alcohol dependence, and alcohol related problems over 12 months.\n Both groups reported substantial reductions in alcohol consumption, dependence, and problems, and better mental health related quality of life over 12 months. Between groups we found only one significant difference in outcome, probably due to chance: the social network group showed significantly better physical health at three months. Non-significant differences at 12 months in the motivational group relative to the social network group included: the number of drinks consumed per drinking day had decreased by an extra 1.1 (95% confidence interval -1.0 to 3.2); scores on the Leeds dependence questionnaire had improved by an extra 0.6 (-0.7 to 2.0); scores on the alcohol problems questionnaire had improved by an extra 0.5 (-0.4 to 1.4); but the number of days abstinent from drinking had increased by 1.2% less (-4.5% to 6.9%).\n The novel social behaviour and network therapy for alcohol problems did not differ significantly in effectiveness from the proved motivational enhancement therapy.", "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.", "To evaluate the effectiveness of medical counselling in reducing alcohol consumption in male heavy drinkers.\n A controlled, randomised, simple-blind intervention study.\n Four Primary Care teams in Area 10, Madrid.\n 152 men who attended for on-demand treatment from the four teams and whose alcohol consumption was over 21 International Units (IU) a week.\n Brief medical counselling backed up by didactic material. Two questionnaires on alcohol consumption in IU, consumption habits and problems related to alcohol were administered, separated by an interval of between 6 and 18 months. Non-parametric tests for paired samples (McNemar) were applied.\n 60% answered the second questionnaire. Neither sociodemographic nor health habit differences were found between those who responded and those who did not, except for social class. There were no appreciable differences between the intervention and control groups. The percentage of drinkers above 35 IU decreased significantly in the intervention group.\n The intervention was clearly effective in reducing the percentage of drinkers whose weekly consumption was over 35 IU.", "We report clinical data on the efficacy of acupuncture for alcohol dependence. 503 patients whose primary substance of abuse was alcohol participated in this randomized, single blind, placebo controlled trial. Patients were assigned to either specific acupuncture, nonspecific acupuncture, symptom based acupuncture or convention treatment alone. Alcohol use was assessed, along with depression, anxiety, functional status, and preference for therapy. This article will focus on results pertaining to alcohol use. Significant improvement was shown on nearly all measures. There were few differences associated with treatment assignment and there were no treatment differences on alcohol use measures, although 49% of subjects reported acupuncture reduced their desire for alcohol. The placebo and preference for treatment measures did not materially effect the results. Generally, acupuncture was not found to make a significant contribution over and above that achieved by conventional treatment alone in reduction of alcohol use.\n Copyright 2002 Elsevier Science Inc." ]

[ "21303529", "15770171", "18775942", "8976475", "16426449", "14965404", "15507794", "19539115", "15967762" ]

[ "A randomised controlled trial of preventive spinal manipulation with and without a home exercise program for patients with chronic neck pain.", "Implementation of the Dutch low back pain guideline for general practitioners: a cluster randomized controlled trial.", "A randomised controlled trial of spinal manipulative therapy in acute low back pain.", "Trunk exercise combined with spinal manipulative or NSAID therapy for chronic low back pain: a randomized, observer-blinded clinical trial.", "Active rehabilitation for chronic low back pain: cognitive-behavioral, physical, or both? First direct post-treatment results from a randomized controlled trial [ISRCTN22714229].", "Implementation of RCGP guidelines for acute low back pain: a cluster randomised controlled trial.", "Early intervention for the management of acute low back pain: a single-blind randomized controlled trial of biopsychosocial education, manual therapy, and exercise.", "A randomized controlled trial comparing 2 types of spinal manipulation and minimal conservative medical care for adults 55 years and older with subacute or chronic low back pain.", "Should treatment of (sub)acute low back pain be aimed at psychosocial prognostic factors? Cluster randomised clinical trial in general practice." ]

[ "Evidence indicates that supervised home exercises, combined or not with manual therapy, can be beneficial for patients with non-specific chronic neck pain (NCNP). The objective of the study is to investigate the efficacy of preventive spinal manipulative therapy (SMT) compared to a no treatment group in NCNP patients. Another objective is to assess the efficacy of SMT with and without a home exercise program.\n Ninety-eight patients underwent a short symptomatic phase of treatment before being randomly allocated to either an attention-group (n = 29), a SMT group (n = 36) or a SMT + exercise group (n = 33). The preventive phase of treatment, which lasted for 10 months, consisted of meeting with a chiropractor every two months to evaluate and discuss symptoms (attention-control group), 1 monthly SMT session (SMT group) or 1 monthly SMT session combined with a home exercise program (SMT + exercise group). The primary and secondary outcome measures were represented by scores on a 10-cm visual analog scale (VAS), active cervical ranges of motion (cROM), the neck disability index (NDI) and the Bournemouth questionnaire (BQ). Exploratory outcome measures were scored on the Fear-avoidance Behaviour Questionnaire (FABQ) and the SF-12 Questionnaire.\n Our results show that, in the preventive phase of the trial, all 3 groups showed primary and secondary outcomes scores similar to those obtain following the non-randomised, symptomatic phase. No group difference was observed for the primary, secondary and exploratory variables. Significant improvements in FABQ scores were noted in all groups during the preventive phase of the trial. However, no significant change in health related quality of life (HRQL) was associated with the preventive phase.\n This study hypothesised that participants in the combined intervention group would have less pain and disability and better function than participants from the 2 other groups during the preventive phase of the trial. This hypothesis was not supported by the study results. Lack of a treatment specific effect is discussed in relation to the placebo and patient provider interactions in manual therapies. Further research is needed to delineate the specific and non-specific effects of treatment modalities to prevent unnecessary disability and to minimise morbidity related to NCNP. Additional investigation is also required to identify the best strategies for secondary and tertiary prevention of NCNP.\n ClinicalTrials.gov: NCT00566930.", "Cluster randomized controlled trial for a multifaceted implementation strategy.\n To assess the effectiveness of tailored interventions (multifaceted implementation strategy) to implement the Dutch low back pain guideline for general practitioners with regard to adherence to guideline recommendations.\n Guidelines for the management of low back pain in primary care have been developed in various countries, but little is known about the optimal implementation strategy. A multifaceted implementation strategy was developed to overcome identified barriers to the implementation of the Dutch low back pain guideline for general practitioners.\n General practitioners were randomized to an intervention or a control group. The general practitioners in the intervention group (n = 21) received tailored interventions consisting of the Dutch low back pain guideline for general practitioners, a 2-hour educational and clinical practice workshop; two scientific articles on low back pain management; the guideline for occupational physicians; a tool for patient education; and a tool for reaching agreement on low back care with physical, exercise, and manual therapists. The control group (n = 20) received no intervention. The participating general practitioners were asked to recruit consecutive patients with a new episode of low back pain as the main reason for consultation. General practitioners completed registration forms of each individual consultation with regard to the main outcome measures: advice and information, referral to other health-care providers, and prescription of medication.\n Forty-one of the 67 randomized general practitioners reported on a total of 616 consultations for 531 patients with nonspecific low back pain. The advice and explanation provided by the general practitioners, the prescription of paracetamol or nonsteroidal anti-inflammatory drugs, and prescription of pain medication on atime contingent or a pain contingent basis showed no statistically significant differences between the intervention and control groups. There were also no differences in overall referral rate. However, in follow-up consultations fewer patients were referred to a physical or exercise therapist by the general practitioners in the intervention group than in the control group.\n The multifaceted intervention strategy modestly improved implementation (for parts of the recommendations in) the Dutch low back pain guideline by general practitioners and produced small concomitant changes in patient management. The implementation strategy produced fewer referrals to therapists during follow-up consultations.", "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.", "To study the relative efficacy of three different treatment for chronic low back pain (CLBP). Two preplanned comparisons were made: (a) Spinal manipulative therapy (SMT) combined with trunk strengthening exercises (TSE) vs. SMT combined with trunk stretching exercises, and (b) SMT combined with TSE vs. nonsteroidal anti-inflammatory drug (NSAID) therapy combined with TSE.\n Interdisciplinary, prospective, observer-blinded, randomized clinical trial with a 1-yr follow-up period. The trial evaluated therapies in combination only and was not designed to test the individual treatment components.\n Primary contact, college out-patient clinic.\n In total, 174 patients aged 20-60 yr were admitted to the study.\n Patient-rated low back pain, disability, and functional health status at 5 and 11 wk.\n Five weeks of SMT or NSAID therapy in combination with supervised trunk exercise, followed by and additional 6 wk of supervised exercise alone.\n Individual group comparisons after 5 and 11 wk of intervention on all three main outcome measures did not reveal any clear clinically important or statistically significant differences. There seemed to be a sustained reduction in medication use at the 1-yr follow-up. in the SMT/TSE group. Continuance of exercise during the follow-up year, regardless of type, was associated with a better outcome.\n Each of the three therapeutic regimens was associated with similar and clinically important improvement over time that was considered superior to the expected natural history of long-standing CLBP. For the management of CLBP, trunk exercise in combination with SMT or NSAID therapy seemed to be beneficial and worthwhile. The magnitude of nonspecific therapeutic (placebo) effects, cost-effectiveness and relative risks of side effects associated with these types of therapy need to be addressed in future studies.", "The treatment of non-specific chronic low back pain is often based on three different models regarding the development and maintenance of pain and especially functional limitations: the deconditioning model, the cognitive behavioral model and the biopsychosocial model. There is evidence that rehabilitation of patients with chronic low back pain is more effective than no treatment, but information is lacking about the differential effectiveness of different kinds of rehabilitation. A direct comparison of a physical, a cognitive-behavioral treatment and a combination of both has never been carried out so far.\n The effectiveness of active physical, cognitive-behavioral and combined treatment for chronic non-specific low back pain compared with a waiting list control group was determined by performing a randomized controlled trial in three rehabilitation centers. Two hundred and twenty three patients were randomized, using concealed block randomization to one of the following treatments, which they attended three times a week for 10 weeks: Active Physical Treatment (APT), Cognitive-Behavioral Treatment (CBT), Combined Treatment of APT and CBT (CT), or Waiting List (WL). The outcome variables were self-reported functional limitations, patient's main complaints, pain, mood, self-rated treatment effectiveness, treatment satisfaction and physical performance including walking, standing up, reaching forward, stair climbing and lifting. Assessments were carried out by blinded research assistants at baseline and immediately post-treatment. The data were analyzed using the intention-to-treat principle.\n For 212 patients, data were available for analysis. After treatment, significant reductions were observed in functional limitations, patient's main complaints and pain intensity for all three active treatments compared to the WL. Also, the self-rated treatment effectiveness and satisfaction appeared to be higher in the three active treatments. Several physical performance tasks improved in APT and CT but not in CBT. No clinically relevant differences were found between the CT and APT, or between CT and CBT.\n All three active treatments were effective in comparison to no treatment, but no clinically relevant differences between the combined and the single component treatments were found.", "The Royal College of General Practitioners (RCGP) has produced guidelines for the management of acute low back pain in primary care.\n To investigate the impact on patient management of an educational strategy to promote these guidelines among general practitioners (GPs).\n Group randomised controlled trial, using the health centre as the unit of randomisation.\n Primary care teams in north-west England.\n Twenty-four health centres were randomly allocated to an intervention or control arm. Practices in the intervention arm were offered outreach visits to promote national guidelines on acute low back pain, as well as access to fast-track physiotherapy and to a triage service for patients with persistent symptoms.\n Twenty-four centres were randomised. Two thousand, one hundred and eighty-seven eligible patients presented with acute low back pain during the study period: 1049 in the intervention group and 1138 in the control group. There were no significant differences between study groups in the proportion of patients who were referred for X-ray, issued with a sickness certificate, prescribed opioids or muscle relaxants, or who were referred to secondary care, but significantly more patients in the intervention group were referred to physiotherapy or the back pain unit (difference in proportion = 12.2%, 95% confidence interval [CI] = 2.8% to 21.6%).\n The management of patients presenting with low back pain to primary care was mostly unchanged by an outreach educational strategy to promote greater adherence to RCGP guidelines among GPs. An increase in referral to physiotherapy or educational programmes followed the provision of a triage service.", "A single blind randomized controlled trial comparing two models of care for patients with acute simple low back pain.\n To compare two research-based models of care for acute low back pain and investigate the effect of the timing of physical intervention.\n National guidelines offer conflicting information on the delivery of physical treatment in the management of acute low back pain. The guidelines suggest two different models of care. Direct comparisons between these models are lacking in the literature. The present study aims to compare these approaches to the management of acute low back pain.\n Among 804 referred patients, 102 subjects met the specific admission criteria and were randomly assigned to an \"assess/advise/treat\" group or an \"assess/advise/wait\" group. The intervention consisted of biopsychosocial education, manual therapy, and exercise. Assessment of short-term outcome enables comparison to be made between intervention and advice to stay active. Assessment of long-term outcome enables comparison to be made between early and late intervention. Study outcomes of reported pain (Visual Analogue Scale), functional disability (the Roland and Morris Disability Questionnaire), mood (Modified Zung Self Rated Depression Score, Modified Somatic Perception Questionnaire, State-Trait Anxiety Inventory), general health (Euroqol), and quality of life (Short Form 36) were assessed at baseline, 6 weeks, 3 months, and 6 months.\n At 6 weeks, the assess/advise/treat group demonstrated greater improvements in disability, mood, general health, and quality of life than patients in the assess/advise/wait group (P < 0.05). Disability and pain were not significantly different between the groups at long-term follow up (P > 0.05). However, mood, general health, and quality of life remained significantly better in the assess/advise/treat group (P < 0.05).\n At short-term, intervention is more effective than advice on staying active, leading to more rapid improvement in function, mood, quality of life, and general health. The timing of intervention affects the development of psychosocial features. If treatment is provided later, the same psychosocial benefits are not achieved. Therefore, an assess/advise/treat model of care seems to offer better outcomes than an assess/advise/wait model of care.", "Chiropractic care is used by many older patients for low back pain (LBP), but there are no published results of randomized trials examining spinal manipulation (SM) for older adults. The purpose of this study was to compare the effects of 2 biomechanically distinct forms of SM and minimal conservative medical care (MCMC) for participants at least 55 years old with subacute or chronic nonradicular LBP.\n Randomized controlled trial. The primary outcome variable was low back-related disability assessed with the 24-item Roland Morris Disability questionnaire at 3, 6, 12, and 24 weeks. Participants were randomly allocated to 6 weeks of care including 12 visits of either high-velocity, low-amplitude (HVLA)-SM, low-velocity, variable-amplitude (LVVA)-SM, or 3 visits of MCMC.\n Two hundred forty participants (105 women and 135 men) ages 63.1 +/- 6.7 years without significant comorbidities. Adjusted mean Roland Morris Disability change scores (95% confidence intervals) from baseline to the end of active care were 2.9 (2.2, 3.6) and 2.7 (2.0, 3.3) in the LVVA-SM and HVLA-SM groups, respectively, and 1.6 (0.5, 2.8) in the MCMC group. There were no significant differences between LVVA-SM and HVLA-SM at any of the end points. The LVVA-SM group had significant improvements in mean functional status ranging from 1.3 to 2.2 points over the MCMC group. There were no serious adverse events associated with any of the interventions.\n Biomechanically distinct forms of SM did not lead to different outcomes in older LBP patients and both SM procedures were associated with small yet clinically important changes in functional status by the end of treatment for this relatively healthy older population. Participants who received either form of SM had improvements on average in functional status ranging from 1 to 2.2 over those who received MCMC. From an evidence-based care perspective, patient preference and clinical experience should drive how clinicians and patients make the SM procedure decision for this patient population.", "To compare the effects of a minimal intervention strategy aimed at assessment and modification of psychosocial prognostic factors and usual care for treatment of (sub)acute low back pain in general practice.\n Cluster randomised clinical trial.\n 60 general practitioners in 41 general practices.\n 314 patients with non-specific low back pain of less than 12 weeks' duration, recruited by their general practitioner.\n In the minimal intervention strategy group the general practitioner explored the presence of psychosocial prognostic factors, discussed these factors, set specific goals for reactivation, and provided an educational booklet. The consultation took about 20 minutes. Usual care was not standardised.\n Functional disability (Roland-Morris disability questionnaire), perceived recovery, and sick leave because of low back pain assessed at baseline and after 6, 13, 26, and 52 weeks.\n The dropout rate was 8% in the minimal intervention strategy group and 9% in the usual care group. Multilevel analyses showed no significant differences between the groups on any outcome measure during 12 months of follow-up in the whole group or in relevant subgroups (patients with high scores on psychosocial measures at baseline or a history of frequent or prolonged low back pain).\n This study provides no evidence that (Dutch) general practitioners should adopt our new treatment strategy aimed at psychosocial prognostic factors in patients with (sub)acute low back pain. Further research should examine why our new strategy was not more effective than usual care." ]

[ "14711910", "9163613", "112475", "8331682", "16714187", "10514159", "7507201", "9403477", "6401878" ]

[ "Efficacy and safety of low-dose aspirin in polycythemia vera.", "Low-dose aspirin in polycythaemia vera: a pilot study. Gruppo Italiano Studio Policitemia (GISP).", "Prevention of thrombosis in patients on hemodialysis by low-dose aspirin.", "Low-dose aspirin and incidence of colorectal tumors in a randomized trial.", "Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.", "Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin.", "Single dose aprotinin in routine cardiac surgery.", "A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group.", "\"AICLA\" controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia." ]

[ "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", "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.", "Since platelet cyclo-oxygenase is much more sensitive to inactivation by aspirin than is the enzyme in the arterial wall and low doses of aspirin may prevent thrombosis by blocking thromboxane synthesis, we conducted a randomized, double-blind trial of aspirin (160 mg per day) vs. placebo in 44 patients on chronic hemodialysis. The study was continued until there were 24 patients with thrombi and both groups had been under observation for a mean of nearly five months. Thrombi occurred in 18 of 25 (72 per cent) of patients given placebo and 16 of 19 (32 per cent) of those given aspirin (P less than 0.01). The incidence of thrombosis was reduced from 0.46 thrombi per patient month in the placebo group to 0.16 thrombi per patient month in the aspirin group (p less than 0.005). A dose of 160 mg of aspirin per day is an effective, nontoxic antithrombotic regimen in patients on hemodialysis.", "Laboratory, clinical, and epidemiologic studies have recently suggested that regular use of aspirin can reduce colorectal cancer incidence or mortality. However, observational epidemiologic analyses have had limited opportunity to control for confounding bias or to specify aspirin doses used.\n Our purpose was to examine the relationship between regular use of low-dose aspirin and incidence of invasive and noninvasive colorectal tumors by utilizing data from the Physicians' Health Study, a randomized, double-blinded, placebo-controlled trial of aspirin and beta carotene. We also attempted to determine whether invasive cancers among aspirin users were associated with rectal bleeding and early stage at diagnosis.\n The Physicians' Health Study includes 22071 U.S. male physicians. The aspirin arm was terminated in 1988 after a mean follow-up of 5 years. Stage at diagnosis and signs and/or symptoms during presentation were abstracted from medical records. Cox proportional hazards models were used to estimate relative risk (RR), 95% confidence intervals (CIs), and the association between aspirin and bleeding. Differences between aspirin and placebo groups in tumor risk over time were visualized with Kaplan-Meier curves. We assessed the association between aspirin and stage at diagnosis with a Mann-Whitney rank sum statistic for non-parametric comparison of two ordinal distributions.\n The RR of developing colorectal cancer for aspirin compared with placebo was 1.15 (95% CI = 0.80-1.65). For in situ cancers and polyps, the RR was 0.86 (95% CI = 0.68-1.10). There was no significant trend for decreasing RR by year of follow-up for invasive cancers (P = .09) or noninvasive tumors (P = .96). Aspirin and placebo groups did not differ in stage or prevalence of rectal bleeding at diagnosis.\n Regular aspirin use, at a dose adequate for preventing myocardial infarction, was not associated with a substantial reduction in the incidence of colorectal cancer during 5 years of randomized treatment and follow-up. A small decrease in polyps in the aspirin group could not be reliably distinguished from a chance association. Our results suggest that among low-dose aspirin users, (a) colorectal cancer mortality is not likely to be reduced by earlier detection and (b) incidence is not likely to be increased due to aspirin-induced gastrointestinal bleeding.\n The potential for a benefit from higher doses of aspirin or longer duration of use should be addressed by more detailed observational epidemiologic studies and prevention trials with longer follow-up of randomized participants.", "Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty.\n We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070).\n Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache.\n The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin.", "To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice.\n Randomised controlled trial.\n 729 patients aged >/=60 years with atrial fibrillation, recruited in general practice, who had no established indication for coumarin. Mean age was 75 years and mean follow up 2. 7 years.\n Primary care in the Netherlands.\n Patients eligible for standard intensity coumarin (international normalised ratio 2.5-3.5) were randomly assigned to standard anticoagulation, very low intensity coumarin (international normalised ratio 1.1-1.6), or aspirin (150 mg/day) (stratum 1). Patients ineligible for standard anticoagulation were randomly assigned to low anticoagulation or aspirin (stratum 2).\n Stroke, systemic embolism, major haemorrhage, and vascular death.\n 108 primary events occurred (annual event rate 5.5%), including 13 major haemorrhages (0.7% a year). The hazard ratio was 0.91 (0.61 to 1.36) for low anticoagulation versus aspirin and 0.78 (0.34 to 1.81) for standard anticoagulation versus aspirin. Non-vascular death was less common in the low anticoagulation group than in the aspirin group (0.41, 0.20 to 0.82). There was no significant difference between the treatment groups in bleeding incidence. High systolic and low diastolic blood pressure and age were independent prognostic factors.\n In a general practice population (without established indications for coumarin) neither low nor standard intensity anticoagulation is better than aspirin in preventing primary outcome events. Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice.", "Evidence exists that the serine protease inhibitor, aprotinin, when used in high dosage, can reduce the bleeding associated with cardiopulmonary bypass. This high dosage is particularly effective in patients at increased risk for bleeding. Less convincing information is available for regimens that use a lower dose and its place in routine cardiac surgery has not been fully resolved. Some studies have shown significant benefit from a single dose added to the cardio-pulmonary bypass prime and we re-examined this alternative. In a randomized, prospective, double-blinded study, we compared this single dose method with placebo in a low risk adults undergoing a first procedure. Benefit was considered established if a significant reduction in blood loss or the use of transfused blood products was seen. We found a significant reduction in red cell transfusion but no improvement in blood loss or blood component transfusion in the treated group. This included patients maintained on aspirin as well as those not receiving aspirin. Aspirin significantly increased blood loss in both control and treatment groups and the usage of blood products in the treatment group. Aprotinin in this low, single dosage was not confirmed as an effective means of improving hemostasis following CPB in routine cardiac surgery.", "Aspirin is only modestly effective in the secondary prevention after cerebral ischemia. Studies in other vascular disorders suggest that anticoagulant drugs in patients with cerebral ischemia of presumed arterial (noncardiac) origin might be more effective. The aim of the Stroke Prevention in Reversible Ischemia Trial (SPIRIT) therefore was to compare the efficacy and safety of 30 mg aspirin daily and oral anticoagulation (international normalized ratio [INR] 3.0-4.5). Patients referred to a neurologist in one of 58 collaborating centers because of a transient ischemic attack or minor ischemic stroke (Rankin grade < or =3) were eligible. Randomization was concealed, treatment assignment was open, and assessment of outcome events was masked. The primary measure of outcome was the composite event \"death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or nonfatal major bleeding complication.\" The trial was stopped at the first interim analysis. A total of 1,316 patients participated; their mean follow-up was 14 months. There was an excess of the primary outcome event in the anticoagulated group (81 of 651) versus 36 of 665 in the aspirin group (hazard ratio, 2.3; 95% confidence interval [CI], 1.6-3.5). This excess could be attributed to 53 major bleeding complications (27 intracranial; 17 fatal) during anticoagulant therapy versus 6 on aspirin (3 intracranial; 1 fatal). The bleeding incidence increased by a factor of 1.43 (95% CI, 0.96-2.13) for each 0.5 unit increase of the achieved INR. Anticoagulant therapy with an INR range of 3.0 to 4.5 in patients after cerebral ischemia of presumed arterial origin is not safe. The efficacy of a lower intensity anticoagulation regimen remains to be determined.", "604 Patients with atherothrombotic cerebral ischemic events (transient, 16%: or completed, 84%) referrable either to the carotid or to the vertebral-basilar circulation were entered into a double blind randomized clinical trial (AICLA) to determine whether aspirin (A) (1 g/day) or aspirin (1 g/day) + Dipyridamole (225 mg/day) (AD) would produce a significant reduction in the subsequent (3 years) occurrence of fatal and nonfatal cerebral infarction. Randomization produced remarkably comparable treatment groups and this good comparability was maintained throughout the study. Adherence to the protocol and drug compliance were excellent. Side effects, particularly symptoms of peptic ulcer and hemorrhagic events were significantly (p less than 0.03) more frequent in the two treatment groups containing aspirin. With the exception of patients who withdrew from the study, each patient was followed for 3 years. At the end of the study, the number of fatal and nonfatal cerebral infarctions was 31 in the placebo (P) group, 17 in the A group and 18 in the AD group. Taking into account the duration of follow-up for each patient, these figures correspond to cumulative rates of 18% in the P group and 10.5% in each of the 2 active treatment groups. Analysis with the Mantel Method showed: 1)--A difference at the 6% level between the 3 groups and between P and AD; 2)--A difference at the 5% level between P and A; 3)--No difference between (A and AD; 4)--A difference at the 2% level between the P group and the two treated groups taken together (A + AD). Among other diseases occurring during the trial, the only significant difference concerned myocardial infarction, which was less frequent in the 2 treated groups (P less than 0.05). Subgroup analysis failed to show a significant sex difference in the efficacy of aspirin. It is concluded that, in patients comparable to those defined in the protocol, Aspirin (1 g) has a significantly beneficial effect in the secondary prevention of atherothrombotic cerebral infarction." ]

[ "16970163", "16418103", "11313839", "16294343", "18162017", "16490019", "16020142", "12851127", "8973666" ]

[ "[Interventional effect of behaviour psychotherapy on patients with premature ejaculation].", "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.", "Pilot intervention to enhance sexual rehabilitation for couples after treatment for localized prostate carcinoma.", "Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial.", "Sexual counseling improved erectile rehabilitation after non-nerve-sparing radical retropubic prostatectomy or cystectomy--results of a randomized prospective study.", "Psychogenic erectile dysfunction: comparative study of three therapeutic approaches.", "The potential benefit of vacuum devices augmenting psychosexual therapy for erectile dysfunction: a randomized controlled trial.", "A double-blind, placebo-controlled evaluation of the erectile response to transurethral alprostadil." ]

[ "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.", "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.", "The majority of prostate carcinoma survivors experience enduring sexual difficulties and associated distress in the years after definitive treatment. A counseling intervention aimed at improving levels of sexual satisfaction and increasing successful utilization of medical treatment for erectile dysfunction (ED) was developed and pilot-tested for both the survivor of prostate carcinoma and his partner.\n All male participants were 3-month to 5-year survivors of localized prostate carcinoma who had been treated with radical prostatectomy or radiation therapy, and were married or in a committed relationship. Couples were randomized to attend four sessions of counseling together or to have the man attend alone. In both groups, partners completed behavioral homework. The sessions included education on prostate carcinoma and sexual function and options to treat ED as well as sexual communication and stimulation skills. Standardized questionnaires at baseline, posttreatment, and at 3-month and 6-month follow-up assessed sexual function, marital adjustment, psychologic distress, and utilization of treatments for ED.\n Fifty-one of 84 couples randomized to treatment completed the intervention (61%). Attendance by the partner did not affect outcomes. Participants completing the intervention demonstrated improvement in male overall distress (P < 0.01), male global sexual function (P < 0.0001), and female global sexual function (P < 0.05) at 3-month follow-up, but regression toward baseline was noted at 6-month follow-up. However, utilization of ED treatments increased from 31% at the time of study entry to 49% at the 6-month follow-up (P = 0.003).\n The results of this brief pilot counseling intervention demonstrated significant gains in sexual function and satisfaction and increased utilization of treatments for ED. However, modifications are needed in future randomized trials to reduce the rate of premature termination and to improve long-term maintenance of gains.\n Copyright 2005 American Cancer Society.", "To investigate if ethyl-eicosapentaenoic acid (E-EPA) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis (FEP).\n We performed a 12-week, randomized, double-blind, placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients. Sixty-nine patients were eligible for analysis; a post hoc analysis was computed for a subgroup of nonaffective FEP patients (N = 53). The first participant was included in November 2000 and the last participant completed the trial in August 2003. Primary outcome measures were symptom change scores and time to first response, while tolerability measures and cumulative antipsychotic dose were secondary outcome measures.\n Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores. Cox regression analysis revealed a significant treatment by diagnosis interaction (p = .024) for time to first response favoring E-EPA in nonaffective psychosis. Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 (42.9% [15/35] vs. 17.6% [6/34] for all participants, p = .036; 54.2% [13/24] vs. 17.2% [5/29] for the nonaffective psychosis subset, p = .008); however, the difference at week 12 was no longer significant. Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20% less antipsychotic medication between weeks 4 through 6 (p = .03), had less extrapyramidal side effects in the initial 9 weeks (p < .05 for all participants and for all timepoints), and reported less constipation (p = .011) and fewer sexual side effects (p = .016) than those treated with antipsychotic medication alone.\n The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications. However, it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis, possibly due to a ceiling effect, since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone. Further controlled trials in nonaffective early psychosis seem warranted.\n Australian Clinical Trials Registry identifier 12605000267651 (http://actr.org.au).", "The efficacy of prostaglandin E1 (PGE1)-intracavernous injection (ICI) therapy for erectile dysfunction (ED) after non-nerve-sparing (NNS) radical pelvic surgery depends on patient compliance. The purpose of this study was to verify the utility of sexual counseling in ICI in terms of treatment efficacy, compliance, and dropout rate.\n In this prospective randomized study, 57 patients with ED after NNS radical prostatectomy or cystectomy were divided: 29 patients (group SC+) were treated with sexual counseling and PGE1-ICI therapy; the others 28 (group SC-) were treated with only ICI. At the start of the study all patients were administered the International Index of Erectile Function (IIEF) questionnaire and ICI training test; follow-up (at 3, 6, 9, 12, 18 months) was achieved by home Sildenafil test and ambulatory IIEF test; sexual counseling was provided only to group SC+.\n The mean IIEF score at the end of study was 26.5 (SC+) vs. 24.3 (SC-) (P < 0.05); eight patients (SC+, 27.5%) became responders to home Sildenafil vs. five (SC-, 17.8%) (P < 0.05); no dropout cases occurred (SC+) vs. eight (SC-, 28.5%) (P < 0.05). Moreover, we recorded best IIEF scores in group SC+ in sexual satisfaction (P < 0.05), sexual desire (P < 0.05), orgasmic function, and general satisfaction. Mean PGE1 doses were better in group SC+ (P < 0.05). ICI-oriented sexual counseling was utilized to motivate couples, to improve sexual intercourses, to correct mistakes in ICI administration. At the end of follow-up 21 patients (SC+) declared themselves satisfied vs. 12 (SC-).\n ICI-oriented sexual counseling in ICI increased the efficacy of treatment, the compliance, and Sildenafil responders rate, decreased the dropout rate.", "We administered the International Index of Erectile Function (IIEF; Rosen et al., 1997) questionnaire to 30 patients with psychogenic erectile dysfunction (ED) at baseline, immediately after treatment, and 3 months after treatment. We randomized patients into three groups: group I, who had weekly sessions of time-limited theme-based group psychotherapy for 6 months and 50 mg sildenafil citrate orally on demand; group II, who had an intake of 50 mg sildenafil citrate orally on demand for 6 months only; and group III, who had weekly sessions of time-limited theme-based group psychotherapy for 6 months. We analyzed data (15-item IIEF) for each group at three times during the study and compared by the data using analysis of variance (ANOVA), followed by the Bonferroni multiple comparison test. We used Cochran's Q-test for analysis between baseline and posttreatment stages of patients with remission of symptoms (EF equal to or higher than 26 points). Group III had a mean score higher than group II, with the difference being statistically significant (immediately after treatment, p = 0.033; at 3 months after treatment, p = 0.049; p < 0.05). All three therapeutic alternatives resulted in an improvement of erectile function domain score. However, significant differences from baseline were observed in groups I (p = 0.0009) and III (p = 0.0002) but not in group II (p = 0.135). The psychotherapy groups, I and III, had significantly higher scores compared with group II, in which patients were exclusively treated with sildenafil citrate. These findings suggest that time-limited theme-based group psychotherapy is an effective treatment for psychogenic ED.", "A cohort of 45 patients diagnosed with predominant psychogenic erectile disorder (ED) chose couples psychotherapy. We randomized 25 couples to also receive a vacuum constriction device (VCD), also known as a vacuum erectile device, at the second session (group 1), whereas 20 couples had psychotherapy without a VCD. Twenty-one couples (84%) in group 1 reported some improvement after the initial psychotherapy and VCD sessions compared with 12 of the 20 couples (60%) who reported some improvement after couples psychotherapy in group 2. We subsequently found that 3 of the 4 couples in group 1 reporting no improvement had not used the pump provided. Early combination treatment of couples psychotherapy and a physical treatment such as a VCD may lead to a greater beneficial response in men with ED than therapy alone. The delay of demonstrating the capacity and potential benefit from a physical intervention may have a marked effect on the initial and ongoing response to sex therapy.", "Previous studies have indicated that the urethra may provide an effective route for administering vasoactive medication for the treatment of erectile dysfunction. We evaluated the safety and efficacy of alprostadil administered intraurethrally at home for the treatment of this disorder.\n This prospective, multicenter, double-blind, placebo-controlled study evaluated the erectile response to randomly assigned doses of transurethral alprostadil at home in 68 men with long-standing (mean 41 months) erectile dysfunction of primarily organic etiology. Patients completing the study each administered a random sequence of four different doses (125, 250, 500, and 1000 micrograms) and placebo over a 2 to 4-week period. Assessments included the couples' ability to have intercourse, patient ratings of erectile response by both categorical and visual analogue scales, penile volume measurements, and overall assessments of comfort and ease of administration.\n Overall, 75.4% (49 of 65) of study patients achieved full enlargement of the penis and 49.2% (32 of 65) achieved an erection judged by the patient to be sufficient for intercourse. In addition, 63.6% (42 of 66) of patients reported intercourse. Efficacy was similar across etiologies. The most common side effect was penile pain, which occurred in association with 9.1% to 18.3% of alprostadil administrations, depending on dose. Mean comfort ratings ranged from 79 to 87, depending on dose, where 0 = severe discomfort and 100 = comfortable; ease of administration scores were above 90 for each dose, where 0 = difficult and 100 = easy. There were no episodes of priapism in this study.\n Short-term treatment with transurethral alprostadil produced erections resulting in sexual intercourse in most patients with chronic erectile dysfunction. This therapy may be a useful treatment option for patients with erectile dysfunction." ]

[ "2029465", "3859744", "10407809", "7796018", "8665186", "1653063", "2957943", "7954233", "16505413" ]

[ "Delta virus and childhood leukemia.", "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].", "Improved outcome for children with hepatoblastoma.", "Adjuvant oral chemotherapy to prevent recurrence after curative resection for hepatocellular carcinoma.", "Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission.", "Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma. A randomized trial.", "Treatment of liver metastases from colorectal cancer with hepatic artery occlusion, intraportal 5-fluorouracil infusion, and oral allopurinol. A randomized clinical trial.", "Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481)." ]

[ "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.", "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.", "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.", "Adjuvant oral chemotherapy was studied in 67 patients with stage II hepatocellular carcinoma who underwent curative resection between May 1988 and December 1990. Patients were stratified into two groups according to preoperative liver dysfunction: 55 had stage I disease (mild dysfunction) and 12 had stage II (moderate dysfunction). A randomized controlled study of postoperative oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) was conducted in each group. From October 1994 HCFU administration was suspended because of side-effects in nine patients with stage I liver dysfunction and in three with stage II dysfunction who had received the drug for more than 4 weeks. Cumulative survival and recurrence-free survival rates of patients with stage I disease in the treatment group were higher (P = 0.08 and P = 0.04 respectively) than those in the control group. However, in patients with stage II disease no significant difference was observed (P = 0.77 and P = 1.0 respectively). This study suggests that the potential benefits of HCFU on tumour recurrence should be weighed against the risk of adverse reactions in patients with mild liver dysfunction.", "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.", "Objective: To compare the efficacy of direct hepatic arterial chemotherapy with systemic chemotherapy in patients with liver metastases from colorectal carcinoma. Design: Randomized trial with crossover allowed from systemic to intrahepatic therapy if tumor progression occurred on systemic therapy. Setting: Academic medical center, referral-based clinic. Patients: One hundred sixty-two patients with hepatic metastases from colorectal carcinoma agreed to be randomly assigned to treatment groups. At laparotomy, 63 were excluded from the study: 25 had hepatic resection; 33, extrahepatic disease; 1, infection; and 4, no tumor. Intervention: Fourteen-day continuous infusion of fluorodeoxyuridine each month using an infusaid pump (0.3 and 0.15 mg/kg body weight X d in the intrahepatic and systemic arms, respectively). Main Results: Intrahepatic therapy produced a significantly higher complete and partial response rate, 50%, compared with 20% for systemic therapy (p = 0.001). After tumor progression, 60% of the systemic patients crossed over to intrahepatic therapy; 25% then had a partial response, and 33% a minor response or stabilization of disease on intrahepatic therapy. Toxicity included ulcer disease (17%) and biliary sclerosis (8%) in patients receiving intrahepatic therapy and diarrhea (70%) in patients receiving systemic therapy. Extrahepatic disease occurred in 56% and 37% of the patients in the intrahepatic and systemic groups, respectively (p = 0.092). The median survivals were 17 and 12 months, for the intrahepatic and systemic groups, respectively. Conclusion: When compared with systemic therapy, hepatic arterial chemotherapy significantly increases response rate for hepatic metastases from colorectal carcinoma and appears to be a more effective treatment.", "Regional therapy for colorectal liver metastases aimed at prolonging survival has not been tested fully in a randomized trial with untreated control subjects. This study explored the efficacy of temporary hepatic artery occlusion followed by intraportal infusion of 5-fluorouracil (5-FU) and oral allopurinol as biochemical modulators in prolonging the survival of patients with nonresectable liver metastases and no extrahepatic cancer.\n Eighty-four patients were considered for randomization, of whom 24 were excluded at laparotomy because of extrahepatic cancer (n = 17) or resectable lesions (n = 5). In two patients, no cancer was identified in the liver. Thirty-two patients were allocated to receive treatment, and 28 were allocated to receive no regional or systemic treatment. Six patients were excluded after randomization because of major protocol violations.\n The median survival time for patients was 17 months (range, 0-66), and for control subjects, the median was 8 months (range, 0-31). Log rank analysis demonstrated a significant survival benefit for treatment versus no treatment (P = 0.0039). (In two patients, early death was due to toxicity from the wrong dose of 5-FU and the wrong route of administration, respectively; the mean and median survival were reduced by 1 month).\n This study identified a treatment modality that prolongs survival in patients with nonresectable liver metastases and no extrahepatic metastases from colorectal cancer, suggesting that control subjects receiving no therapy may not be necessary in future randomized trials.", "Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome.\n In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers.\n Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade > or = 3 neutropenia (2% and 45%; P < .01), stomatitis (0% and 24%; P < .01), and bilirubin elevation (18.6% and 0; P < .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or > or = 4, the median survival was 24 and 14 months, respectively (P = .17).\n HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents." ]

[ "15113492", "14760042", "7748631", "11116772", "11939381", "10480824", "15120768", "1483075", "18237352" ]

[ "Exploratory cluster randomised controlled trial of shared care development for long-term mental illness.", "The North Dublin randomized controlled trial of structured diabetes shared care.", "Coordinating and standardizing long-term care: evaluation of the west of Scotland shared-care scheme for hypertension.", "Patient-held shared care records for individuals with mental illness. Randomised controlled evaluation.", "Randomized controlled trial to assess the effectiveness of a primary health care liaison worker in promoting shared care for opiate users.", "Multifaceted shared care intervention for late life depression in residential care: randomised controlled trial.", "Evaluation of a short-term group intervention for informal carers of patients attending a home palliative care service.", "Randomised controlled trial of effects of coordinating care for terminally ill cancer patients.", "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews." ]

[ "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 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.", "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.", "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.", "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.", "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.", "Despite evidence of high psychological distress and unmet needs, evaluated interventions for informal caregivers in palliative care are few. This study involved an observational outcome evaluation of attendees, and a comparison group, in specialist home palliative care. The measures included carer psychological status and patient physical status at baseline, 8 weeks, and 20 weeks. Qualitative data were collected regarding content, satisfaction with, and impact of intervention. Process data described the uptake, resources, and group activity. The intervention combined informal multiprofessional teaching with facilitated peer exchange and support, and was delivered over 6 sessions of 90 minutes per week. The uptake rate was 25%; carers were less likely to accept if they were in paid employment (OR=0.26, P=0.06), and more likely to accept if they utilized avoidance coping (OR=1.13, P=0.04) or their patient had worse physical status (OR=2.1, P=0.03). Attendees described significant support and knowledge gains from the multiprofessional input and peer group. Most relied on social comparison processes to appraise their situation. Potential detection of significant effects on global psychological scores (i.e. anxiety, depression, and burden) using multivariate analysis was disallowed due to attrition. This acceptable and accessible intervention provided information and support; further outcome studies are needed for a range of interventions. Short-term interventions are unlikely to affect global psychological scores, and future evaluations should include additional time points of data collection to demonstrate support during attendance.", "To measure effects on terminally ill cancer patients and their families of coordinating the services available within the NHS and from local authorities and the voluntary sector.\n Randomised controlled trial.\n Inner London health district.\n Cancer patients were routinely notified from 1987 to 1990. 554 patients expected to survive less than one year entered the trial and were randomly allocated to a coordination or a control group.\n All patients received routinely available services. Coordination group patients received the assistance of two nurse coordinators, whose role was to ensure that patients received appropriate and well coordinated services, tailored to their individual needs and circumstances.\n Patients and carers were interviewed at home on entry to the trial and at intervals until death. Interviews after bereavement were also conducted. Outcome measures included the presence and severity of physical symptoms, psychiatric morbidity, use of and satisfaction with services, and carers' problems. Results from the baseline interview, the interview closest to death, and the interview after bereavement were analysed.\n Few differences between groups were significant. Coordination group patients were less likely to suffer from vomiting, were more likely to report effective treatment for it, and less likely to be concerned about having an itchy skin. Their carers were more likely to report that in the last week of life the patient had had a cough and had had effective treatment for constipation, and they were less likely to rate the patient's difficulty swallowing as severe or to report effective treatment for anxiety. Coordination group patients were more likely to have seen a chiropodist and their carers were more likely to contact a specialist nurse in a night time emergency. These carers were less likely to feel angry about the death of the patient.\n This coordinating service made little difference to patient or family outcomes, perhaps because the service did not have a budget with which it could obtain services or because the professional skills of the nurse-coordinators may have conflicted with the requirements of the coordinating role.", "There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one-off evaluations rather than impact evaluations with long-term follow-up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high-quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low- and middle-income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC. Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass-media and patient-mediated interventions may change professional practice. Multifaceted interventions that combine several quality-improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration. The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no 'magic bullets' or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision-makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality-improvement activities, priority setting, selection and design of interventions, and evaluation." ]

[ "20008886", "17854523", "15608037", "18335226", "19357861", "15925049", "15533377", "15755044", "15979994" ]

[ "Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT).", "A prospective randomized study comparing coasting with GnRH antagonist administration in patients at risk for severe OHSS.", "GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial.", "Comparison of multiple dose GnRH antagonist and minidose long agonist protocols in poor responders undergoing in vitro fertilization: a randomized controlled trial.", "Comparing GnRH agonist long protocol and GnRH antagonist protocol in outcome the first cycle of ART.", "A randomised study of GnRH antagonist (cetrorelix) versus agonist (busereline) for controlled ovarian stimulation: effect on safety and efficacy.", "A modified gonadotropin-releasing hormone (GnRH) antagonist protocol failed to increase clinical pregnancy rates in comparison with the long GnRH protocol.", "Use of a GnRH antagonist in controlled ovarian hyperstimulation for assisted conception in women with polycystic ovary disease: a randomized, prospective, pilot study.", "A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists." ]

[ "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.", "This work evaluated possible advantages of gonadotrophin-releasing hormone (GnRH) antagonist administration as an alternative to coasting in prevention of severe ovarian hyperstimulation syndrome (OHSS) in women undergoing IVF/ intracytoplasmic sperm injection. A prospective randomized study comparing coasting (group A) (n = 96) and GnRH antagonist administration (group B) (n = 94) in patients at risk of OHSS was performed. The primary outcome measure was high quality embryos. The secondary outcome measures were days of intervention, number of oocytes, pregnancy rate, number of cryopreserved embryos and incidence of severe OHSS. There were significantly more high quality embryos (2.87 +/- 1.2 versus 2.21 +/- 1.1; P < 0.0001), and more oocytes (16.5 +/- 7.6 versus 14.06 +/- 5.2; P = 0.02), in group B as compared with group A. There were more days of coasting as compared with days of antagonist administration (2.82 +/- 0.97 versus 1.74 +/- 0.91; P < 0.0001). In conclusion, GnRH antagonist was superior to coasting in producing significantly more high quality embryos and more oocytes as well as reducing the time until HCG administration. There was no significant difference in pregnancy rate between the two groups. No OHSS developed in either group.", "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 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.", "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.", "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.", "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.", "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.", "Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH antagonists remains to be assessed.\n 106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established.\n No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52).\n Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH antagonists." ]

[ "7980301", "7769899", "12057549", "2180472", "9532990", "10533328", "7791836", "12540643", "8616125" ]

[ "A safer and more effective treatment regimen for eclampsia.", "Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial.", "Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial.", "Magnesium sulphate versus diazepam in the management of eclampsia: a randomized controlled trial.", "A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia.", "Efficacy of magnesium sulphate and phenytoin in the management of eclampsia.", "A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia.", "A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia.", "Randomised study assessing the effect of phenytoin and magnesium sulphate on maternal cerebral circulation in eclampsia using transcranial Doppler ultrasound." ]

[ "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.", "Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains an important cause of maternal mortality. Although it is standard practice to use an anticonvulsant for management of eclampsia, the choice of agent is controversial and there has been little properly controlled evidence to support any of the options. 1687 women with eclampsia were recruited into an international multicentre randomised trial comparing standard anticonvulsant regimens. Primary measures of outcome were recurrence of convulsions and maternal death. Data are available for 1680 (99.6%) women: 453 allocated magnesium sulphate versus 452 allocated diazepam, and 388 allocated magnesium sulphate versus 387 allocated phenytoin. Most women (99%) received the anticonvulsant that they had been allocated. Women allocated magnesium sulphate had a 52% lower risk of recurrent convulsions (95% CI 64% to 37% reduction) than those allocated diazepam (60 [13.2%] vs 126 [27.9%]; ie, 14.7 [SD 2.6] fewer women with recurrent convulsions per 100 women; 2p < 0.00001). Maternal mortality was non-significantly lower among women allocated magnesium sulphate. There were no significant differences in other measures of serious maternal morbidity, or in perinatal morbidity or mortality. Women allocated magnesium sulphate had a 67% lower risk of recurrent convulsions (95% CI 79% to 47% reduction) than those allocated phenytoin (22 [5.7%] vs 66 [17.1%] ie, 11.4 [SD 2.2] fewer women with recurrent convulsions per 100 women; 2p < 0.00001). Maternal mortality was nonsignificantly lower among women allocated magnesium sulphate. Women allocated magnesium sulphate were also less likely to be ventilated, to develop pneumonia, and to be admitted to intensive care facilities than those allocated phenytoin. The babies of women who had been allocated magnesium sulphate before delivery were significantly less likely to be intubated at the place of delivery, and to be admitted to a special care nursery, than the babies of mothers who had been allocated phenytoin. There is now compelling evidence in favour of magnesium sulphate, rather than diazepam or phenytoin, for the treatment of eclampsia.", "Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate.\n Eligible women (n=10141) had not given birth or were 24 h or less postpartum; blood pressure of 140/90 mm Hg or more, and proteinuria of 1+ (30 mg/dL) or more; and there was clinical uncertainty about magnesium sulphate. Women were randomised in 33 countries to either magnesium sulphate (n=5071) or placebo (n=5070). Primary outcomes were eclampsia and, for women randomised before delivery, death of the baby. Follow up was until discharge from hospital after delivery. Analyses were by intention to treat.\n Follow-up data were available for 10,110 (99.7%) women, 9992 (99%) of whom received the allocated treatment. 1201 of 4999 (24%) women given magnesium sulphate reported side-effects versus 228 of 4993 (5%) given placebo. Women allocated magnesium sulphate had a 58% lower risk of eclampsia (95% CI 40-71) than those allocated placebo (40, 0.8%, vs 96, 1.9%; 11 fewer women with eclampsia per 1000 women). Maternal mortality was also lower among women allocated magnesium sulphate (relative risk 0.55, 0.26-1.14). For women randomised before delivery, there was no clear difference in the risk of the baby dying (576, 12.7%, vs 558, 12.4%; relative risk 1.02, 99% CI 0.92-1.14). The only notable difference in maternal or neonatal morbidity was for placental abruption (relative risk 0.67, 99% CI 0.45-0.89).\n Magnesium sulphate halves the risk of eclampsia, and probably reduces the risk of maternal death. There do not appear to be substantive harmful effects to mother or baby in the short term.", "This randomized controlled trial compared the use of magnesium sulphate with diazepam as anticonvulsant in 51 eclamptic women. The use of magnesium sulphate was associated with less serious morbidity (in terms of recurrence of convulsions, cardiopulmonary problems, disseminated intravascular coagulopathy, and acute renal failure) but the difference was not statistically significant (relative risk 0.6; 95% CI 0.3 to 1.2). The one maternal death occurred in the magnesium sulphate group. Convulsions recurred in five (21%) women in the magnesium sulphate group and seven (26%) women in the diazepam group. Urine output poor enough to prompt diuretic stimulation was less frequent in the magnesium sulphate group than in the diazepam group (RR 0.3; 95% CI 0.1 to 0.9). Significantly fewer infants born in the magnesium sulphate group had low Apgar scores (less than 7 at 1 min) compared with those in the diazepam group (RR 0.6; 95% CI 0.4 to 0.9). There were two early neonatal deaths in the magnesium sulphate group, and three stillbirths in the diazepam group. This study suggests that magnesium sulphate has advantages over diazepam for the mother and the infant in the treatment of eclampsia, but the trial is small and should be replicated on a larger scale.", "To determine whether the administration of prophylactic intravenous magnesium sulphate reduces the occurrence of eclampsia in women with severe pre-eclampsia.\n Randomised controlled trial.\n A tertiary referral obstetric unit.\n Eight hundred and twenty-two women with severe pre-eclampsia requiring termination of pregnancy by induction of labour or caesarean section.\n The women were randomised to receive either placebo (saline) or magnesium sulphate intravenously. The investigators were blinded to the contents of the pre-mixed solutions.\n The occurrence of eclampsia in the two groups.\n The data of 699 women were evaluated. Fourteen were withdrawn after randomisation. The overall incidence of eclampsia was 1.8%. Of 345 women who received magnesium sulphate, one developed eclampsia (0.3%); in the placebo group, 11/340 women (3.2%) developed eclampsia (relative risk 0.09; 95% confidence interval 0.01-0.69; P = 0.003).\n The use of intravenous magnesium sulphate in the management of women with severe pre-eclampsia significantly reduced the development of eclampsia.", "Fifty pregnant women admitted with diagnosis of eclampsia were randomly allocated to magnesium sulphate (Group A) or phenytoin sodium (Group B) treatment group. Incidence of recurrence of seizures maternal as well as perinatal morbidity and mortality were compared in both the groups. Mean maternal age, parity and gestational age was similar in both the groups. Mean birth weight was significantly lower in Group B compared to Group A. Seizure frequency prior to hospitalization was 5.4 +/- 4.7 in Group A and 4.8-3.6 in Group B. Mean time interval between occurrence of first seizure and hospitalization was 9.6 +/- 3.5 hours in Group A and 11.8 +/- 9.3 hours in Group B, the difference was not statistically significant. Women treated with phenytoin had a higher incidence of recurrent seizures (10/25-40%) than those treated with magnesium sulphate (2/25-8%). Majority of the women treated with phenytoin (6/10-60%) had single convulsion after initiation of anticonvulsant therapy and 1 woman of each group had recurrent convulsions (75). There was no significant difference in perinatal outcome in both the groups. Maternal morbidity was comparable in both the groups and there was no maternal death in either of the groups.", "Magnesium sulfate is used widely to prevent eclamptic seizures in pregnant women with hypertension, but few studies have compared the efficacy of magnesium sulfate with that of other drugs. Anticonvulsant prophylaxis with phenytoin for eclampsia has been recommended, but there are virtually no data to support its efficacy. Our objective was to compare magnesium sulfate with phenytoin in preventing seizures in hypertensive women during labor.\n We randomly assigned women with hypertension who were admitted for delivery to receive either magnesium sulfate or phenytoin. The magnesium sulfate regimen consisted of a 10-g intramuscular loading dose followed by a maintenance dose of 5 g given intramuscularly every four hours. For women with severe preeclampsia, an additional 4-g loading dose was given intravenously. The phenytoin regimen included a 1000-mg loading dose infused over a period of 1 hour, followed by a 500-mg oral dose 10 hours later. With either regimen, anticonvulsant therapy was continued for 24 hours post partum.\n Ten of 1089 women randomly assigned to the phenytoin regimen had eclamptic convulsions, as compared with none of 1049 women randomly assigned to magnesium sulfate (P = 0.004). There were no significant differences in any risk factors for eclampsia between the two study groups. Maternal and infant outcomes were also similar in the two study groups.\n Magnesium sulfate is superior to phenytoin for the prevention of eclampsia in hypertensive pregnant women. These results validate the long-practiced use of magnesium sulfate in the prevention of eclampsia.", "Magnesium sulfate may prevent eclampsia by reducing cerebral vasoconstriction and ischemia. Nimodipine is a calcium-channel blocker with specific cerebral vasodilator activity. Our objective was to determine whether nimodipine is more effective than magnesium sulfate for seizure prophylaxis in women with severe preeclampsia.\n We conducted an unblinded, multicenter trial in which 1650 women with severe preeclampsia were randomly assigned to receive either nimodipine (60 mg orally every 4 hours) or intravenous magnesium sulfate (given according to the institutional protocol) from enrollment until 24 hours post partum. High blood pressure was controlled with intravenous hydralazine as needed. The primary outcome measure was the development of eclampsia, as defined by a witnessed tonic-clonic seizure.\n Demographic and clinical characteristics were similar in the two groups. The women who received nimodipine were more likely to have a seizure than those who received magnesium sulfate (21 of 819 [2.6 percent] vs. 7 of 831 [0.8 percent], P=0.01). The adjusted risk ratio for eclampsia associated with nimodipine, as compared with magnesium sulfate, was 3.2 (95 percent confidence interval, 1.1 to 9.1). The antepartum seizure rates did not differ significantly between groups, but the nimodipine group had a higher rate of postpartum seizures (9 of 819 [1.1 percent] vs. 0 of 831, P=0.01). There were no significant differences in neonatal outcome between the two groups. More women in the magnesium sulfate group than in the nimodipine group needed hydralazine to control blood pressure (54.3 percent vs. 45.7 percent, P<0.001).\n Magnesium sulfate is more effective than nimodipine for prophylaxis against seizures in women with severe preeclampsia.\n Copyright 2003 Massachusetts Medical Society", "To assess maternal middle cerebral artery flow velocity patterns as measured by transcranial Doppler ultrasound (TCD) in eclampsia and to investigate the effect of the anticonvulsants magnesium sulphate (MgSO4) and phenytoin on cerebral circulation.\n Prospective randomised study.\n High care obstetric unit, King Edward VIII Hospital, Durban, South Africa.\n Twenty-four eclamptic patients: 13 received MgSO4 and 11 phenytoin.\n Middle cerebral artery flow velocity waveforms were measured using 2 MHz pulsed Doppler ultrasound via the transtemporal approach in eclamptic patients, before and 15 minutes after the loading dose of anticonvulsant.\n Magnesium sulphate significantly reduced the pulsatility index (P = 0.002) and mean flow velocity (P = 0.02) in the middle cerebral artery, whereas phenytoin failed to produce any statistically significant effect. However, differences between groups were not statistically significant. Systolic and diastolic blood pressures were reduced in both the MgSO4 and phenytoin groups.\n These findings provide firm evidence that MgSO4 relieves cerebral vasospasm, compared with phenytoin, and may therefore be the better drug for the prevention of eclamptic convulsion." ]

[ "16549460", "16634838", "17392542", "14633804", "17718288", "20854384", "19734396", "17563345", "15334379" ]

[ "Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients.", "Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2.", "The effect of cinnamon on A1C among adolescents with type 1 diabetes.", "Cinnamon improves glucose and lipids of people with type 2 diabetes.", "The effect of cinnamon cassia powder in type 2 diabetes mellitus.", "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.", "Effect of cinnamon on glucose and lipid levels in non insulin-dependent type 2 diabetes.", "Effect of Pancreas Tonic (an ayurvedic herbal supplement) in type 2 diabetes mellitus." ]

[ "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.", "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.", "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.", "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.", "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.", "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.", "nan", "Although there is widespread use of herbal dietary supplements that are believed to benefit type 2 diabetes mellitus, few have been proven to do so in properly designed randomized trials; their efficacy for intermediate-term glucose control remains unclear. Pancreas Tonic is a botanical mixture of traditional Indian Ayurvedic herbs currently available as a dietary supplement. We report the results of a single-center, randomized, double-blind, placebo-controlled 3-month trial of Pancreas Tonic in type 2 diabetic patients inadequately treated with diet/lifestyle or stable doses of sulfonylureas and/or metformin for at least 3 months. Patients with type 2 diabetes for >/= 1 year were entered into 2 strata of hemoglobin A(1c) (HbA(1c)) levels (stratum 1: 8.0% to 9.9%; stratum 2: 10.0% to 12.0%). All subjects began a 1-month single-blind placebo run-in phase, followed by randomization in a 2:1 ratio of active treatment: placebo, to 3 months of double-blind treatment with either Pancreas Tonic or matching placebo (2 capsules 3 times a day). Concurrent oral agents were continued unchanged throughout the study. The primary outcome was the change in HbA(1c) from randomization; results of each stratum were analyzed independently. The baseline characteristics of 36 subjects who completed the study were comparable between treatment groups. Nineteen subjects entered stratum 1 and 17 entered stratum 2. A statistically significant reduction of HbA(1c) from randomization to end-of-study was seen in the stratum 2 subjects (Pancreas Tonic: 10.1% +/- 1.0% to 8.8% +/- 1.9%, P =.004; placebo: 10.8% +/- 1.4% to 11.2% +/- 1.8%, not significant [NS]). No significant HbA(1c) reductions were seen in the stratum 1 subjects. There were no significant treatment-related differences in the fasting plasma glucose (FPG), lipids, body mass index (BMI), body composition, blood pressure, insulin sensitivity estimates using the minimal model, glucose and insulin responses to a meal challenge, quality of life, adverse events, or other safety indices between treatment groups. Pancreas Tonic was well tolerated. Treatment with Pancreas Tonic (2 capsules 3 times per day) for 3 months significantly improved glucose control in type 2 diabetic patients with HbA(1c) levels between 10.0% to 12.0%. This study represents the first properly designed, prospective intervention trial of therapy with an Ayurvedic herbal supplement for intermediate-term glucose control in type 2 diabetes." ]

[ "2046107", "12473876", "7795830", "8467308", "14654762", "1764497", "16647628", "12435255", "490882" ]

[ "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.", "Non-pharmacological treatment of hypertension in primary health care: a 2-year open randomized controlled trial of lifestyle intervention against hypertension in eastern Finland.", "Trial of Nonpharmacologic Intervention in the Elderly (TONE). Design and rationale of a blood pressure control trial.", "Evaluation of a structured treatment and teaching programme on hypertension in general practice.", "Results of the pilot study for the Hypertension in the Very Elderly Trial.", "Syst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: objectives, protocol, and organization.", "Pharmaceutical care program for patients with uncontrolled hypertension. Report of a double-blind clinical trial with ambulatory blood pressure monitoring.", "Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.", "Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative 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.", "To assess whether lifestyle counselling is effective in non-pharmacological treatment of hypertension in primary health care.\n Open randomized controlled trial.\n Ten municipal primary health care centres in eastern Finland.\n Seven hundred and fifteen subjects aged 25-74 years with systolic blood pressure 140-179 mmHg and/or diastolic blood pressure 90-109 mmHg or antihypertensive drug treatment.\n Systematic health counselling given by local public health nurses for 2 years.\n Blood pressure, lipids and lifestyle data were collected annually.\n Among participants with no antihypertensive drug treatment, the net reductions after 1 year both in systolic blood pressure [-2.6 mmHg; 95% confidence interval (CI), -4.7 to -0.5 mmHg] and in diastolic blood pressure (-2.7 mmHg; 95% CI, -4.0 to -1.4 mmHg) were significant in favour of the intervention group. This difference in blood pressure change was maintained during the second year. In participants with antihypertensive drug treatment, no significant difference in blood pressure reduction was seen between the groups during the study.\n A relatively modest, but systematic counselling in primary health care can, at least among untreated hypertensive subjects, produce reductions in blood pressure levels that are modest for the individual, but very important from the public health point of view.", "National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure (BP). However, data to support such recommendations in older persons are virtually nonexistent. The Trials of Nonpharmacologic Intervention in the Elderly (TONE) is a randomized, controlled trial that will test whether weight loss or a reduced sodium (Na) intake or both can maintain satisfactory BP control, without unacceptable side effects, after withdrawal of antihypertensive drug therapy. Medication-treated hypertensives (aged 60 to 80 years) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are randomly assigned to one of four groups: (1) weight loss alone, (2) reduced Na intake alone, (3) combined weight loss and reduced Na intake, or (4) usual life-style (control group). Overweight participants are randomized to one of these four groups, while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group. The interventions, tailored to the needs of older persons, use behavioral approaches to accomplish intervention-specific goals (weight loss > or = 10 lb, daily Na intake < or = 80 mEqa). Three months after the start of intervention, antihypertensive drug therapy is withdrawn. The primary trial end point is a BP of 150/90 mm Hg or higher, resumption of antihypertensive drug therapy, or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up. It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy.", "Evaluation of a structured hypertension treatment and teaching programme in general practice.\n Prospective controlled trial; follow-up period 18 months.\n 10 primary health care practices. PRACTICES AND PATIENTS: From each practice 20 patients (30 to 60 years old, mean of the last two blood pressure measurements at or above 160 and/or 95 mmHg) were randomly selected; in 5 practices these patients were to participate in the treatment and teaching programme; in the remaining 5 practices hypertension care was continued without the availability of such a programme (controls).\n Structured treatment and teaching programme based upon four group sessions for patients mainly conducted by paramedical personnel.\n Blood pressure, body weight, prescription of antihypertensive drugs - as documented in the patient's records.\n Of the 100 control patients 26 and of the 100 intervention patients 14 were lost to observation; 46 patients had agreed to participate in the programme. The mean number of prescribed antihypertensive agents per patient decreased in the intervention group (1.8 +/- 1.3 at baseline, vs 1.2 +/- 1.2 at follow-up) compared to the control group (1.6 +/- 1.3 vs 1.8 +/- 1.6); difference 0.8 (95% CI 0.4 to 1.1), p < 0.0001. In the control group 9% and in the intervention group 33% of patients had documented reductions of body weight (p < 0.0001). Blood pressure decreased in the intervention group (162 +/- 14/100 +/- 7 mmHg at baseline, vs 154 +/- 16/95 +/- 9 mmHg at follow-up) compared to the control group (161 +/- 13/98 +/- 7 mmHg vs 158 +/- 18/96 +/- 11 mmHg); differences for systolic blood pressure 5 (95% CI 0 to 10) mmHg, p = 0.071; for diastolic blood pressure 4 (1 to 7) mmHg, p = 0.018.\n The introduction of a structured hypertension treatment and teaching programme in general practice may lead to significant improvements of hypertension care.", "The risks and benefits of treating hypertension in individuals older than 80 years are uncertain. A meta-analysis has suggested that a reduction in stroke events of 36% may have to be balanced against a 14% increase in total mortality.\n To report the results of the pilot study of the Hypertension in the Very Elderly Trial (HYVET), which is in progress to address these issues.\n The HYVET-Pilot was a multicentre international open pilot trial. In 10 European countries, 1283 patients older than 80 years and with a sustained blood pressure of 160-219/90-109 mmHg were allocated randomly to one of three treatments: a diuretic-based regimen (usually bendroflumethiazide; n = 426), an angiotensin-converting enzyme inhibitor regimen (usually lisinopril; n = 431) or no treatment (n = 426). The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment. Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months.\n In the combined actively treated groups, the reduction in stroke events relative hazard rate (RHR) was 0.47 [95% confidence interval (CI) 0.24 to 0.93] and the reduction in stroke mortality RHR was 0.57 (95% CI 0.25 to 1.32). However, the estimate of total mortality supported the possibility of excess deaths with active treatment (RHR 1.23, 95% CI 0.75 to 2.01).\n The preliminary results support the need for the continuing main HYVET trial. It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 (nine non-fatal), but may be associated with 20 extra non-stroke deaths.", "The Syst-Eur Trial is a concerted action of the European Community's Medical and Health Research Programme. The trial is carried out in consultation with the World Health Organization, the International Society of Hypertension, the European Society of Hypertension and the World Hypertension League. This article describes the objectives and the protocol of Syst-Eur, a multicentre trial designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality. Secondary endpoints include cardiovascular events, such as myocardial infarction and congestive heart failure. To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic pressure less than 95 mmHg. Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry. The patients are randomized to active treatment or placebo. Active treatment consists of nitrendipine (10-40 mg/day), combined with enalapril (5-20 mg/day) and hydrochlorothiazide (12.5-25 mg/day), as necessary. The patients of the control group receive matching placebos. The drugs (or matching placebos) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg. Morbidity and mortality are monitored to enable an intention-to-treat and per-protocol comparison of the outcome in the 2 treatment groups. A one-year pilot trial (1989) showed that the protocol is practicable. The Ethics Committee therefore decided to start the definite study (1990), in which randomized patients will be followed for 5 years. Recruitment of new centres and of the required 3,000 patients will last 3 years (until 1993).", "Pharmaceutical care programs may be an option to improve blood pressure (BP) control in patients with uncontrolled hypertension. The aim of this study was to evaluate the efficacy of pharmaceutical care programs in treating patients with resistant hypertension.\n In a double-blind randomized clinical trial, 71 patients with uncontrolled BP were enrolled in a pharmaceutical care program or in a control group and underwent a series of cognitive tests. The primary outcome was change in ambulatory BP (ABP) between the baseline evaluation and the final visit 6 months later. The secondary outcomes were the frequency of drug-related problems and adherence as determined by plasma levels of hydrochlorothiazide.\n The delta-values between the intervention and control groups for ABP in the different daily periods, with the corresponding 95% confidence limits, adjusted for age and baseline BP were: 3 (-1 to 5), 2 (-2 to 4), and 5 (-1 to 6) mm Hg for 24 h, daily and nightly systolic BP, respectively. The corresponding values for diastolic BP were 1 (-1 to 3), 0 (-2 to 2), and 3 (-1 to 4) mm Hg, respectively. Hydrochlorothiazide was detected in the plasma in 21 of 27 patients in the intervention group that attended to all appointments and 24 of 30 patients in the control group (P = .904).\n The pharmaceutical care program tested in this trial was feasible and showed a trend for better BP control in patients with uncontrolled hypertension.", "Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD.\n To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension.\n Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998.\n A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years.\n Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals.\n Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol.\n Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups.\n No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.", "The Hypertension Detection and Follow-up Program (HDFP), in a community-based, randomized controlled trial involving 10,940 persons with high blood pressure (BP), compared the effects on five-year mortality of a systematic antihypertensive treatment program (Stepped Care [SC]) and referral to community medical therapy (Referred Care [RC]). Participants, recruited by population-based screening of 158,906 people aged 30 to 69 years in 14 communities througout the United States, were randomly assigned to SC or RC groups within each center and by entry diastolic blood pressure (DBP) (90 to 104, 105 to 114, and 115 + mm Hg). Over the five years of the study, more than two thirds of the SC participants continued to receive medication, and more than 50% achieved BP levels within the normotensive range, at or below the HDFP goal for DBP. Controls of BP was consistently better for the SC than for the RC group. Five-year mortality from all causes was 17% lower for the SC group compared to the RC group (6.4 vs 7.7 per 100, P less than .01) and 20% lower for the SC subgroup with entry DBP of 90 to 104 mm Hg compared to the corresponding RC subgroup (5.9 vs 7.4 per 100, P less than .01). These findings of the HDFP indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large numbers of people with high BP in the population, including those with \"mild\" hypertension." ]

[ "18580613", "20823434", "18977721", "19549342", "20415574", "15630469", "16052084", "20163349", "12599045" ]

[ "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.", "Virologic, immunologic, clinical, safety, and resistance outcomes from a long-term comparison of efavirenz-based versus nevirapine-based antiretroviral regimens as initial therapy in HIV-1-infected persons.", "Medication diaries do not improve outcomes with highly active antiretroviral therapy in Kenyan children: a randomized clinical trial.", "Early versus delayed initiation of antiretroviral therapy for concurrent HIV infection and cryptococcal meningitis in sub-saharan Africa.", "Randomized, controlled trial of therapy interruption in chronic HIV-1 infection.", "A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers.", "Results of a community-based antiretroviral treatment program for HIV-1 infection in Western Uganda.", "A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1." ]

[ "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.", "To compare long-term virologic, immunologic, and clinical outcomes in antiretroviral-naïve persons starting efavirenz (EFV)- versus nevirapine (NVP)-based regimens.\n The FIRST study randomized patients into three strategy arms: PI+NRTI, NNRTI+NRTI, and PI+NNRTI+NRTI. NNRTI was determined by optional randomization (NVP or EFV) or by choice. For this randomized substudy, the primary endpoint was HIV RNA >50 copies/mL after 8 months or death. Genotypic resistance testing was done at virologic failure (VF; HIV RNA >1,000 copies/mL at or after 4 months).\n 228 persons (111 randomized to EFV, 117 to NVP) were followed for median 5 years. Rates per 100 person years for the primary endpoint were 41.2 (EFV) and 42.8 (NVP; p = .59). The percent of persons with HIV RNA <50 copies/mL was similar throughout follow-up (p = .24), as were average increases in CD4+ cells (p = .30). 423 persons declining the substudy chose EFV; 264 chose NVP. There were 915 persons in the combined cohort (randomized and choice). In the combined cohort, the risk of VF and VF with any NNRTI or NRTI resistance or resistance of any class was significantly less for EFV compared to NVP.\n EFV-based regimens as initial therapy resulted in a lower risk of VF and VF with resistance than did NVP-based regimens, although immunologic and clinical outcomes were similar.", "As highly active antiretroviral therapy (HAART) becomes increasingly available to African children, it is important to evaluate simple and feasible methods of improving adherence in order to maximize benefits of therapy.\n HIV-1-infected children initiating World Health Organization non-nucleoside reverse transcriptase-inhibitor-containing first-line HAART regimens were randomized to use medication diaries plus counselling, or counselling only (the control arm of the study). The diaries were completed daily by caregivers of children randomized to the diary and counselling arm for nine months. HIV-1 RNA, CD4+ T cell count, and z-scores for weight-for-age, height-for-age and weight-for-height were measured at a baseline and every three to six months. Self-reported adherence was assessed by questionnaires for nine months.\n Ninety HIV-1-infected children initiated HAART, and were followed for a median of 15 months (interquartile range: 2-21). Mean CD4 percentage was 17.2% in the diary arm versus 16.3% in the control arm at six months (p = 0.92), and 17.6% versus 18.9% at 15 months (p = 0.36). Virologic response with HIV-1 RNA of <100 copies/ml at nine months was similar between the two arms (50% for the diary arm and 36% for the control, p = 0.83). The weight-for-age, height-for-age and weight-for-height at three, nine and 15 months after HAART initiation were similar between arms. A trend towards lower self-reported adherence was observed in the diary versus the control arm (85% versus 92%, p = 0.08).\n Medication diaries did not improve clinical and virologic response to HAART over a 15-month period. Children had good adherence and clinical response without additional interventions. This suggests that paediatric HAART with conventional counselling can be a successful approach. Further studies on targeted approaches for non-adherent children will be important.", "BACKGROUND. Cryptococcal meningitis (CM) remains a leading cause of acquired immunodeficiency syndrome-related death in sub-Saharan Africa. The timing of the initiation of antiretroviral therapy (ART) for human immunodeficiency virus (HIV)-associated CM remains uncertain. The study aimed to determine the optimal timing for initiation of ART in HIV-positive individuals with CM. METHODS. A prospective, open-label, randomized clinical trial was conducted at a tertiary teaching hospital in Zimbabwe. Participants were aged > or = 18 years, were ART naive, had received a first CM diagnosis, and were randomized to receive early ART (within 72 h after CM diagnosis) or delayed ART (after 10 weeks of treatment with fluconazole alone). Participants received 800 mg of fluconazole per day. The ART regimen used was stavudine, lamivudine, and nevirapine given twice daily. The duration of follow-up was up to 3 years. The primary end point was all-cause mortality. RESULTS. Fifty-four participants were enrolled in the study (28 in the early ART arm and 26 in the delayed ART arm). The median CD4 cell count at enrollment was 37 cells/mm(3) (interquartile range, 17-69 cells/mm(3)). The 3-year mortality rate differed significantly between the early and delayed ART groups (88% vs 54%; P < .006); the overall 3-year mortality rate was 73%. The median durations of survival were 28 days and 637 days in the early and delayed ART groups, respectively (P = .031, by log-rank test). The risk of mortality was almost 3 times as great in the early ART group versus the delayed ART group (adjusted hazard ratio, 2.85; 95% confidence interval, 1.1-7.23). The study was terminated early by the data safety monitoring committee. CONCLUSIONS. In resource-limited settings where CM management may be suboptimal, when compared with a delay of 10 weeks after a CM diagnosis, early initiation of ART results in increased mortality. Trial registration. ClinicalTrials.gov identifier: NCT00830856.", "Approaches to limiting exposure to antiretroviral therapy (ART) drugs are an active area of HIV therapy research. Here we present longitudinal follow-up of a randomized, open-label, single-center study of the immune, viral, and safety outcomes of structured therapy interruptions (TIs) in patients with chronically suppressed HIV-1 infection as compared to equal follow-up of patients on continuous therapy and including a final therapy interruption in both arms.\n Forty-two chronically HIV-infected patients on suppressive ART with CD4 counts higher than 400 were randomized 1:1 to either (1) three successive fixed TIs of 2, 4, and 6 wk, with intervening resumption of therapy with resuppression for 4 wk before subsequent interruption, or (2) 40 wk of continuous therapy, with a final open-ended TI in both treatment groups. Main outcome was analysis of the time to viral rebound (>5,000 copies/ml) during the open-ended TI. Secondary outcomes included study-defined safety criteria, viral resistance, therapy failure, and retention of immune reconstitution. There was no difference between the groups in time to viral rebound during the open-ended TI (continuous therapy/single TI, median [interquartile range] = 4 [1-8] wk, n = 21; repeated TI, median [interquartile range] = 5 [4-8] wk, n = 21; p = 0.36). No differences in study-related adverse events, viral set point at 12 or 20 wk of open-ended interruption, viral resistance or therapy failure, retention of CD4 T cell numbers on ART, or retention of lymphoproliferative recall antigen responses were noted between groups. Importantly, resistance detected shortly after initial viremia following the open-ended TI did not result in a lack of resuppression to less than 50 copies/ml after reinitiation of the same drug regimen.\n Cycles of 2- to 6-wk time-fixed TIs in patients with suppressed HIV infection failed to confer a clinically significant benefit with regard to viral suppression off ART. Also, secondary analysis showed no difference between the two strategies in terms of safety, retention of immune reconstitution, and clinical therapy failure. Based on these findings, we suggest that further clinical research on the long-term consequences of TI strategies to decrease drug exposure is warranted.", "Single-dose nevirapine (NVP) prophylaxis to mother and infant is widely used in resource-constrained settings for preventing mother-to-child transmission (MTCT) of HIV-1. Where women do not access antenatal care or HIV testing, postexposure prophylaxis to the infant may be an important preventative strategy.\n This multicentre, randomized, open-label clinical trial (October 2000 to September 2002) in South Africa compared single-dose NVP with 6 weeks of zidovudine (ZDV), commenced within 24 h of delivery among 1051 infants whose mothers had no prior antiretroviral therapy. HIV-1 infection rates were ascertained at birth, and at 6 and 12 weeks of age. Kaplan-Meier survival methods were used to estimate HIV-1 infection rates in an intention-to-treat analysis.\n Overall, 6 week and 12 week MTCT probability was 12.8% [95% confidence interval (CI),10.5-15.0] and 16.3% (95% CI,13.4-19.2), respectively. At 12 weeks, among infants who were not infected at birth, 24 (7.9%) infections occurred in the NVP arm and 41 (13.1%) in the ZDV arm (log rank P = 0.06). Using multivariate analysis, factors associated with infection following birth were ZDV use [odds ratio (OR), 1.8; 95% CI,1.1-3.2; P = 0.032), maternal CD4 cell count < 500 x 10(6) cells/l (OR, 2.5; 95% CI,1.3-5.0; P = 0.007), maternal viral load > 50 000 copies/ml (OR, 3.6; 95% CI,2.0-6.2; P < 0.0001) and breastfeeding (OR, 2.2; 95% CI,1.3-3.8; P = 0.006).\n A single-dose of NVP given to infants offers protection against HIV-1 infection and should be a strategy used in infants of mothers with untreated HIV infection.", "To compare the treatment outcomes and mortality in a rural community-based ART (CBART) program with a hospital-based ART program in the same district.\n The study design was a non-randomized cohort study consisting of 185 persons living with HIV (PLWHIV) in the CBART cohort and 200 PLWHIV in the hospital cohort. Eligibility for both cohorts was: being HIV-infected and eligible for ART, being treatment naïve, age 18 years or older, and being a resident of Rwimi sub-county. The intervention consisted of a community-based program which included weekly home visits to patients by trained volunteers who delivered antiretroviral drugs (ARVs), monitored and supported adherence to treatment, and identified and reported adverse reactions and other clinical symptoms. Outcome variables were compared to patients in a hospital-based cohort who received the standard care delivered to all other HIV patients in the hospital. The main outcome measures were HIV-1 RNA viral load (VL), CD4 cell count and mortality after six months of treatment.\n Successful ART treatment outcome as measured by virological suppression (VL<400 copies/ml) in the CBART cohort were similar to those in the hospital-based cohort (90.1% vs 89.3%, p=0.47). The median CD4 cell count increased significantly in both cohorts (community-based cohort 159 cells/microl vs 145 cells/microl in the hospital-based cohort). Mortality was not significantly different in both cohorts (community-based cohort 11.9%, hospital-based cohort 9.0%).\n The findings show that outcomes of a CBART intervention in a rural area compare favorably to outcomes of hospital-based care. If the study results are sustainable over a longer time period, this model could be considered for ART roll-out to impoverished rural/remote populations in Uganda and elsewhere.", "To determine the efficacy and safety of 2 inexpensive and easily deliverable antiretroviral (ARV) regimens for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 during labor and delivery, HIV-infected pregnant women were screened at 11 maternity health institutions in South Africa and were enrolled in an open-label short course ARV regimen of either nevirapine (Nvp) or multiple-dose zidovudine and lamivudine (Zdv/3TC). The overall estimated HIV-1 infection rates in 1307 infants by 8 weeks were 12.3% (95% confidence interval [CI], 9.7-15.0) for Nvp and 9.3% (95% CI, 7.0-11.6) for Zdv/3TC (P=.11). Excluding infections detected within 72 h (intrauterine), new HIV-1 infections were detected in 5.7% (95% CI, 3.7-7.8) and 3.6% (95% CI, 2.0-5.3) of infants in the Nvp and Zdv/3TC groups, respectively, in the 8 weeks after birth. There were no drug-related maternal or pediatric serious adverse events. Common complications were obstetrical for mothers (Nvp group, 24.3%; Zdv/3TC group, 26.3%) and respiratory for infants (Nvp group, 16.1%; Zdv/3TC group, 17.0%). This study further confirms the efficacy and safety of short-course ARV regimens in reducing MTCT rates in developing countries." ]

[ "15746784", "17318804", "16327491", "16034832", "11485528", "15798459", "16491462", "15666380", "17457160" ]

[ "Sharp liver transection versus clamp crushing technique in liver resections: a prospective study.", "Randomized clinical trial of radiofrequency-assisted versus clamp-crushing liver resection.", "How should transection of the liver be performed?: a prospective randomized study in 100 consecutive patients: comparing four different transection strategies.", "Randomized clinical trial of the effect of a saline-linked radiofrequency coagulator on blood loss during hepatic resection.", "Randomized comparison of ultrasonic vs clamp transection of the liver.", "Complete versus selective portal triad clamping for minor liver resections: a prospective randomized trial.", "Randomized clinical trial of the effects of abdominal drainage after elective hepatectomy using the crushing clamp method.", "Ischemic preconditioning in deceased donor liver transplantation: a prospective randomized clinical trial of safety and efficacy.", "Intraoperative blood salvage during liver resection: a randomized controlled trial." ]

[ "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.", "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.", "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.", "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.", "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.", "To evaluate the feasibility, safety, efficacy, amount of hemorrhage, postoperative complications, and ischemic injury of selective clamping in patients undergoing minor liver resections.\n Inflow occlusion can reduce blood loss during hepatectomy. However, Pringle maneuver produces ischemic injury to the remaining liver. Selective hemihepatic vascular occlusion technique can reduce the severity of visceral congestion and total liver ischemia.\n Eighty patients undergoing minor hepatic resection were randomly assigned to complete clamping (CC) or selective clamping (SC). Hemodynamic parameters, including portal pressure and the hepatic venous pressure gradient (HVPG), were evaluated. The amount of blood loss, measurements of liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and postoperative evolution were also recorded.\n No differences were observed in the amount of hemorrhage (671 +/- 533 mL versus 735 +/- 397 mL; P = 0.54) or the patients that required transfusion (10% versus 15%; P = 0.55). There were no differences on postoperative morbidity between groups (38% versus 29%; P = 0.38). Cirrhotic patients with CC had significantly higher ALT (7.7 +/- 4.6 versus 4.5 +/- 2.7 mukat/L, P = 0.01) and AST (10.2 +/- 8.7 versus 4.9 +/- 2.1 mukat/L; P = 0.03) values on the first postoperative day than SC. The multivariate analysis demonstrated that high central venous pressure, HVPG >10 mm Hg, and intraoperative blood loss were independent factors related to morbidity.\n Both techniques of clamping are equally effective and feasible for patients with normal liver and undergoing minor hepatectomies. However, in cirrhotic patients selective clamping induces less ischemic injury and should be recommended. Finally, even for minor hepatic resections, central venous pressure, HVPG, and intraoperative blood loss are factors related to morbidity and should be considered.", "Abdominal drainage is a standard procedure after hepatectomy, but this practice has been challenged recently.\n Between September 2004 and March 2005, 120 consecutive patients who had undergone hepatic resection by the same surgical team were randomly allocated into drainage and no drainage groups (60 in each group). Patient characteristics, preoperative liver function, presence of cirrhosis, resection-related factors and postoperative complications were compared between the two groups.\n The groups were comparable in terms of demographics, indications for surgery, preoperative liver function test results, presence of cirrhosis, extent of hepatectomy, intraoperative blood loss and requirement for blood transfusion. Symptomatic subphrenic collection and pleural effusion occurred in four patients (7 per cent) who had abdominal drainage and three (5 per cent) who did not. Local wound complications occurred in 17 (28 per cent) and two (3 per cent) patients respectively (P < 0.001). The postoperative hospital stay was similar in the two groups. Multivariate analysis indicated that the presence of cirrhosis and abdominal drainage were independently related to the development of postoperative wound complications.\n Routine abdominal drainage is unnecessary after elective hepatectomy using the crushing clamp method.", "Ischemic preconditioning (IPC) has the potential to decrease graft injury and morbidity after liver transplantation. We prospectively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers randomized 1:1 to standard (STD) recovery (N = 28) or IPC (N = 34). Safety was assessed by measurement of heart rate, blood pressure, and visual inspection of abdominal organs during recovery, and efficacy by recipient aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT], both measured in U/L), total bilirubin, and international normalized ratio of prothrombin time (INR) after transplantation. IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion. Recipient median AST, median ALT, and mean INR, in STD vs. IPC were as follows: day 1 AST 696 vs. 841 U/L; day 3 AST 183 vs. 183 U/L; day 1 ALT 444 vs. 764 U/L; day 3 ALT 421 vs. 463 U/L; day 1 INR 1.7 +/- .4 vs. 2.0 +/- .8; and day 3 INR 1.3 +/- .2 vs. 1.4 +/- .3; all P > .05. No instances of nonfunction occurred. The 6-month graft and patient survival STD vs. IPC were 82 vs. 91% and median hospital stay was 10 vs. 8 days; both P > .05. In conclusion, deceased donor livers tolerated 5 minutes of hilar clamping well, but IPC did not decrease graft injury. Further trials with longer periods of preconditioning such as 10 minutes are needed.", "A randomized controlled trial was conducted to clarify the effectiveness of intraoperative blood salvage in reducing blood loss.\n Although reduction of central venous pressure (CVP) is thought to decrease blood loss during liver resection, no consistently effective and safe method for obtaining the desired reduction of CVP has been established.\n Living liver donors scheduled to undergo liver graft procurement were randomly assigned to a blood salvage group, in which a blood volume equal to approximately 0.7% of the patient's body weight was collected before the liver transection, or a control group. The surgeons were blinded to the randomization results. The primary outcome measure was blood loss during liver parenchymal division. A multivariate analysis was also performed.\n Seventy-nine donors were allocated intraoperatively to the blood salvage group (n = 40) or the control group (n = 39). The amount of blood loss during liver transection was significantly smaller in the blood salvage group than in the control group (median loss during transection, 140 mL vs. 230 mL, P = 0.034). The CVP at the beginning of the liver parenchymal division was significantly lower in the blood salvage group than in the control group (median, 5 cm H2O vs. 6 cm H2O, P = 0.005). The results of a multivariate analysis revealed that intraoperative blood salvage offered the advantage of reduced blood loss during liver parenchymal division (adjusted OR, 0.31; 95% CI, 0.11-0.85, P = 0.025).\n Modest intraoperative blood salvage significantly and safely reduced blood loss during hepatic parenchymal transection." ]

[ "18672987", "17240933", "8267871", "8941832", "19161059", "10530095", "16881807", "12699051", "8144738" ]

[ "Comparison of the use of different modes of mechanical oral hygiene in prevention of plaque and gingivitis.", "A clinical investigation of the efficacy of three different treatment regimens for the control of plaque and gingivitis.", "A comparison of the Braun Oral-B Plaque Remover (D5) electric and a manual toothbrush in affecting gingivitis.", "Clinical evaluation of an ionic toothbrush in the removal of established plaque and reduction of gingivitis.", "Evaluation of an educational program for children with high risk of caries.", "A 3-month clinical investigation comparing the safety and efficacy of a novel electric toothbrush (Braun Oral-B 3D Plaque Remover) with a manual toothbrush.", "Clinical efficacy of flossing versus use of antimicrobial rinses.", "The efficacy of an essential oil antiseptic mouthrinse vs. dental floss in controlling interproximal gingivitis: a comparative study.", "Comparison of a manual and a new electric toothbrush for controlling plaque and gingivitis." ]

[ "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.", "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.", "This three-month clinical trial was designed to compare the effect of an electric and a manual toothbrush on reducing primarily gingivitis and secondarily, plaque, in a cohort of 70 healthy adults. After baseline evaluation of gingivitis, soft tissue trauma, and plaque, patients were randomly assigned to one of the two experimental groups, shown an instructional tooth brushing videotape, and had their teeth cleaned. Soft tissue trauma was again scored at 2 weeks. At 12 weeks all three clinical parameters were again evaluated. The results showed statistically significant reductions (baseline vs. 3-month) in both whole mouth (p = 0.003) and interproximal (p = 0.008) gingivitis scores for the electric toothbrush group. No significant reduction at three months compared to baseline was seen for the manual brush group. When gingivitis reductions were compared over the three-month test period, the electric brush was significantly better than the manual toothbrush in both whole mouth (p = 0.0007) and interproximal (p = 0.002) gingivitis reduction. No increase in soft tissue trauma and no significant differences in plaque reductions were seen for either toothbrush.", "The clinical effectiveness of a manual ionic toothbrush in the removal of dental plaque and the reduction of gingivitis was evaluated. A double-blind study evaluated the effect of a small, imperceptible electric current on established dental plaque and gingivitis during toothbrushing. Sixty-four adults completed the study. Gingivitis and plaque scores were determined at baseline and after 3 and 6 months. The baseline indices of the two groups were well balanced. At each examination, the participants were instructed how to hold the toothbrush properly and reminded to change brush heads every 4 weeks. Statistically significant improvements in Löe Gingival Index scores were observed from baseline to 6 months between the control and test groups and within the test group. The Quigley-Hein Plaque Index scores also showed a significant improvement from baseline to 6 months between the control and test groups and within the test group.", "The goal of this study was to evaluate a 15-month educational program designed to children. The sample consisted of 60 six-year olds, randomly assigned into control and experimental group. The control consisted of tooth brushing training, once a year. The experimental group received intensive individual tooth brushing training every three months and guidance on oral health. Initially, both groups were assessed using plaque, gingival, dmfs and DMF-S indexes every three months. In the control, no statistically significant difference was observed for plaque and gingival indexes. The experimental group showed a statistically significant reduction in mean values for two indexes. The caries indexes showed no statistically significant difference. The proposed educational program developed was efficient in reducing gingival and plaque indexes as well caries incidence.", "To compare the efficacy and safety of a novel electric toothbrush (Braun Oral-B 3D Plaque Remover) with a standard reference ADA manual toothbrush.\n 114 subjects were included in a 3-month randomized, parallel group, examiner-blind study and divided into two groups: 3D users and manual toothbrush users. Subjects were instructed to brush twice daily for 2 minutes. Evaluation of oral soft and hard tissue for safety, plaque, gingivitis and bleeding was conducted prior to the start of product use (at baseline), at days 14 and 35, and at 3 months.\n 105 subjects (55 3D users and 50 manual toothbrush users) completed the study. At days 14, 35 and at 3 months both groups showed reductions from baseline in whole mouth plaque, gingivitis and bleeding that were statistically significant (P < 0.005), except in the case of plaque at day 35 in manual toothbrush users. At 3 months, reductions for whole mouth plaque, gingivitis and bleeding were 15%, 16% and 65%, for 3D users and 8%, 12% and 56%, for manual toothbrush users, respectively. Group differences were significant (P < 0.05) in favor of the 3D with respect to plaque reduction for the whole mouth and for interproximal and anterior lingual sites at all three time periods. With respect to gingivitis, reductions for the whole mouth and interproximal and posterior lingual sites at 3 months were significantly greater in the 3D group. There was no clinically significant soft or hard tissue abrasion in either group. In conclusion, the 3D electric toothbrush was found to be safe and had increased efficacy with respect to reduction of plaque and gingivitis compared to a manual toothbrush.", "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.", "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.", "In the present clinical trial, the effect on existing plaque and gingivitis of a new electric toothbrush (ET) was compared to that of a manual toothbrush (MT). 40 medical students, age 18-30 years, participated. Plaque index (PlI) and gingival index (GI) were recorded at 6 sites at all teeth. At baseline, a PlI and GI > 1 were required. The participants were at random allocated to a group using either ET or MT and were instructed only to use the assigned toothbrush, brushing each morning and evening for 2 min. No oral hygiene instruction was given. Re-examination was done after 1, 2 and 6 weeks. In the MT group, a minor decrease in mean PlI was found after 6 weeks (all sites: from 1.2 to 1.1, approximal sites: from 1.4 to 1.2). The corresponding figures in the ET group were: 1.2 to 0.6 and 1.4 to 0.8. After 6 weeks, the % of sites with visible plaque with MT was: 24% (all sites) and 30% (approximal sites) and with ET 8% and 9%, respectively. With MT, mean GI was unchanged after 6 weeks compared to baseline, whereas with ET, the changes were from 1.1 to 0.9 (all sites) and from 1.1 to 1.0 (approximal sites). The % of sites with GI score > or = 2 had not changed after 6 weeks with MT (all sites: 11%, approximal sites: 13%). With ET, these results were 3% and 4%, respectively." ]

[ "10952698", "6366725", "9212042", "11076326", "20463094", "15588235", "2196355", "8030684", "14630985" ]

[ "Randomised trial of iodine intake and thyroid status in preterm infants.", "Results of controlled double-blind study of thyroid replacement in very low-birth-weight premature infants with hypothyroxinemia.", "L-thyroxine treatment of preterm newborns: clinical and endocrine effects.", "Postnatal thyroxine supplementation in infants less than 32 weeks' gestation: effects on pulmonary morbidity.", "Thyroid hormone early adjustment in pregnancy (the THERAPY) trial.", "Effects of increased thyroxine dosage pre-conception on thyroid function during early pregnancy.", "Prenatal and postnatal corticosteroid therapy to prevent neonatal necrotizing enterocolitis: a controlled trial.", "A randomized, controlled trial of antepartum thyrotropin-releasing hormone and betamethasone in the prevention of respiratory disease in preterm infants.", "A randomized, masked study of triiodothyronine plus thyroxine administration in preterm infants less than 28 weeks of gestational age: hormonal and clinical effects." ]

[ "Low levels of circulating thyroid hormones have been associated with poorer general and neurodevelopmental outcome in preterm babies and it has been speculated that the association is causal. Low levels of circulating thyroid hormone have been reported after inadequate intake of iodine in preterm infants being fed milk formula.\n To investigate whether increased iodine intake from supplemented preterm formula would improve thyroid hormone levels in preterm babies (this study) and hence improve neurodevelopmental status (planned subsequent study).\n A total of 121 preterm infants were entered into a randomised controlled trial of standard (68 microg/l) versus increased (272 microg/l) iodine in preterm formula.\n The two groups were comparable at recruitment. No evidence of an effect of the intervention on thyroid hormone levels was seen up to 41 weeks after conception.\n Calls for increased iodine content of preterm infant formulas are not justified by this study.", "The nature of hypothyroxinemia in sick very low-birth-weight (VLBW) infants was evaluated by assessment of the hypothalamic-pituitary axis and by the clinical response to thyroxine (T4) therapy. Twenty-three very low-birth-weight infants of gestational age 26 to 28 weeks, whose serum T4 concentrations were 4 micrograms/dL on two occasions, and thyrotropin less than 20 microU/mL, were included in a double-blind study. Following a thyrotropin-releasing hormone stimulation test, babies were given either T4 or placebo. Nine babies were thyrotropin-releasing hormone tested prior to therapy; four babies, two from each group, were tested 1 to 2 weeks after therapy. In 11 untreated babies, mean base line serum thyrotropin of 7.0 +/- 1.4 rose to 23.7 +/- 4.1 microU/mL in 30 minutes. This response was not significantly greater than the observed response in full-term babies, 23.7 +/- 4.1 v 16.6 +/- 0.97 microU/mL, respectively, P greater than .05. In two babies treated with T4 the thyrotropin response to thyrotropin-releasing hormone was completely suppressed. Serial serum T4 determinations showed normalization in both groups after a similar time interval. There was no beneficial effect of T4 therapy on growth of head circumference, length, or weight. Developmental data revealed no significant differences in the mental, motor, or gross neurologic outcome in the treated and nontreated infants after 1 year of follow-up. These observations imply that hypothyroxinemia in sick preterm infants is not a direct consequence of hypothyroidism. Despite the lack of demonstrable short-term beneficial effects of T4 therapy, follow-up studies are necessary to resolve the question of long-term benefits.", "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.", "Thyroid hormone requirement increases 20-40% during gestation. Women with treated hypothyroidism must increase their l-T(4) in pregnancy to prevent maternal hypothyroidism, although how this should be accomplished is unclear.\n We prospectively enrolled 60 women with treated hypothyroidism seeking pregnancy. Once pregnant, women were randomized to increase l-T(4) by either two tablets/wk (group A) or three tablets/wk (group B). Thyroid function was tested biweekly through midpregnancy and at 30 wk gestation. Levothyroxine was adjusted to maintain goal TSH concentrations. The primary objective was to assess efficacy in preventing maternal hypothyroidism and the safety of this intervention.\n Forty-eight women completed the protocol. Increasing the l-T(4) dose once pregnant (regardless of study arm) prevented TSH elevation over 5.0 mIU/liter throughout the first trimester and replicated physiological changes of pregnancy. The early l-T(4) increase caused TSH suppression below 0.5 mIU/liter in eight of 25 women in group A compared with 15 of 23 women in group B (P < 0.01). This risk was significantly increased in athyreotic patients [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 1.1-11.1], those with prepregnancy TSH less than 1.5 mIU/liter (OR = 4.6; 1.3-16.2), and those receiving prepregnancy l-T(4) doses of 100 microg/d or more (OR = 7.2; 1.7-30.6). However, if a trimester-specific TSH lower reference range of 0.1 mIU/liter was used, only two patients (8%) in group A required dose reduction. TSH testing every 4 wk identifies 92% of abnormal values.\n A two-tablet increase in l-T(4) initiated at confirmation of pregnancy significantly reduces the risk of maternal hypothyroidism during the first trimester and mimics normal physiology. Monitoring TSH every 4 wk through midgestation is recommended.", "To compare the effects of pregnancy on the serum free thyroxine (FT4) levels in two cohorts of primary hypothyroid women treated with different levothyroxine (L-T4) doses before gestation.\n Twenty-five women with compensated hypothyroidism of different aetiology (thyroidectomized and Hashimoto's thyroiditis) were enrolled in this prospective study. The women were receiving substitutive doses of L-T4 and were anticipating pregnancy. They were assigned to two groups: 14 patients (group I) were switched to partially suppressive treatment while 11 patients (group II) continued the same therapeutic regimen.\n Pre-conceptional thyroid function evaluation demonstrated significantly higher FT4 and lower TSH in group I (P<0.001, for both hormones) and comparable free 3,5,3'-triiodothyronine (FT3) levels. The first post-conception thyroid function evaluation occurred at a median time of 6 (5-8) and 7 (5-9) weeks of gestation, for groups I and II respectively (P<0.05); all women in group I showed adequate serum FT4 levels while three patients in group II showed low-normal FT4 levels and one case was below normal levels. Statistical analysis demonstrated significantly higher frequencies (0% vs 36.4%; P<0.05) of low-normal FT4 levels in patients receiving substitutive doses of L-T4. None of the Hashimoto's-affected patients showed low or low-normal serum FT4 levels regardless of their therapeutic regimen.\n Our results suggest that in hypothyroid women anticipating pregnancy (with serum TSH in the lower quartile of normal range), the pre-conception adjustment of L-T4 doses may result in adequate maternal thyroid function up to the first post-conception evaluation. The procedure seems safe and inexpensive; it may be a worthwhile treatment, at least in thyroidectomized women, in view of the well-known potential effects of even marginal maternal thyroid hypofunction on the subsequent IQ of the progeny.", "To determine whether prenatal corticosteroid therapy would reduce the incidence of neonatal necrotizing enterocolitis (NEC), we assigned a total of 466 women admitted in premature labor either to receive placebo (group A, n = 256), if delivery was expected to occur within 24 hours of admission, or to receive betamethasone (group B, n = 210) if delivery was expected to take place more than 24 hours after admission. All women were free of severe medical complications or drug therapy; cases of intrauterine growth retardation or premature rupture of the membranes were excluded. Their newborn infants, excluding malformed, congenitally infected, and growth-retarded infants, were enrolled in the study unless they had died before the age of 10 postnatal days. Babies born to group A mothers (n = 248) were further assigned to a treatment group (group A1, n = 130) receiving dexamethasone, 2 mg/kg/day by intravenous injection during the first 7 days of life, or to a control group (group A2, n = 118) receiving 10% dextrose solution placebo. Group B infants (prenatal betamethasone, n = 205) received neither treatment nor placebo. The incidence of NEC in group A1 was 6.9% (9/130), and in group A2 it was 14.4% (17/118) (p less than 0.05). In group B the incidence was 3.4% (7/205); this was much lower than in group A2 (p less than 0.01) and lower than in group A combined (10.4%) (p less than 0.01). There was no death from NEC and no surgical intervention among group B patients. The mortality rate for group A1 (11%) was lower than for group A2 (56%) (p less than 0.02). There were fewer indications for surgical intervention for NEC in group A1 than in group A2. Histologic studies confirmed bowel ischemia in all specimens analyzed. These data support the hypothesis that the incidence of NEC is significantly reduced after prenatal steroid treatment. Although postnatal therapy with steroids does not decrease the incidence as effectively as prenatal therapy, it improves clinical outcome of NEC.", "The objective was to investigate whether the addition of thyrotropin-releasing hormone to antepartum betamethasone further reduces the incidence of respiratory disease in preterm infants.\n A randomized, placebo-controlled, double-blind trial of antepartum thyrotropin-releasing hormone (400 micrograms given intravenously four times) and betamethasone (5 mg given intramuscularly four times) was conducted in 378 mothers likely to be delivered between 24 and 32.6 weeks' gestation. Statistical analysis was by relative risk, chi 2, t tests, and multiple logistic regression analysis.\n Four hundred five live-born infants were delivered. In infants without lethal abnormalities delivered between 24 hours and 10 days from entry (n = 175) the incidence of respiratory distress syndrome was reduced from 52% to 31% (relative risk 0.61, 95% confidence interval 0.41 to 0.89) and that of severe respiratory distress syndrome from 42% to 20% (relative risk 0.48, 95% confidence interval 0.29 to 0.78) in the placebo and thyrotropin-releasing hormone groups, respectively. The number of deaths fell from 14 to one (relative risk 0.08, 95% confidence interval 0.01 to 0.63). The incidence of chronic lung disease was not significantly different, but that of an adverse outcome (chronic lung disease or death by 36 weeks' gestation) fell from 29% in the placebo group to 16% with thyrotropin-releasing hormone (relative risk 0.55, 95% confidence interval 0.31 to 0.99).\n The addition of thyrotropin-releasing hormone to antepartum glucocorticoid treatment reduces the incidence of respiratory distress syndrome and improves survival in preterm infants.", "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." ]

[ "12554890", "1642520", "10557684", "9476870", "12195271", "17149995", "22054336", "11059522", "8520339" ]

[ "Breathing retraining for dysfunctional breathing in asthma: a randomised controlled trial.", "Deep diaphragmatic breathing: rehabilitation exercises for the asthmatic patient.", "Can small group education and peer review improve care for patients with asthma/chronic obstructive pulmonary disease?", "A randomized trial comparing peak expiratory flow and symptom self-management plans for patients with asthma attending a primary care clinic.", "Asthma in adolescents: a randomized, controlled trial of an asthma program for adolescents and young adults with severe asthma.", "Use and impact of an automated telephone outreach system for asthma in a managed care setting.", "Enhancing ventilation in homes of children with asthma: pragmatic randomised controlled trial.", "A clinical trial of the Buteyko Breathing Technique in asthma as taught by a video.", "Do clinical guidelines introduced with practice based education improve care of asthmatic and diabetic patients? A randomised controlled trial in general practices in east London." ]

[ "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.", "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.", "To study the effectiveness of an intensive small group education and peer review programme aimed at implementing national guidelines on asthma/chronic obstructive pulmonary disease (COPD) on care provision by general practitioners (GPs) and on patient outcomes.\n A randomised experimental study with pre-measurement and post-measurement (after one year) in an experimental group and a control group in Dutch general practice.\n Two groups of GPs were formed and randomised. The education and peer review group (17 GPs with 210 patients) had an intervention consisting of an interactive group education and peer review programme (four sessions each lasting two hours). The control group consisted of 17 GPs with 223 patients (no intervention).\n Knowledge, skills, opinion about asthma and COPD care, presence of equipment in practice; actual performance about peakflow measurement, non-pharmacological and pharmacological treatment; asthma symptoms (Dutch Medical Research Council), smoking habits, exacerbation ratio, and disease specific quality of life (QOL-RIQ). Data were collected by a written questionnaire for GPs, by self recording of consultations by GPs, and by a written self administered questionnaire for adult patients with asthma/COPD.\n Data from 34 GP questionnaires, 433 patient questionnaires, and recordings from 934 consultations/visits and 350 repeat prescriptions were available. Compared with the control group there were only significant changes for self estimated skills (+16%, 95% confidence interval 4% to 26%) and presence of peakflow meters in practice (+18%, p < 0.05). No significant changes were found for provided care and patient outcomes compared with the control group. In the subgroup of more severe patients, the group of older patients, and in the group of patients not using anti-inflammatory medication at baseline, no significant changes compared with the control group were seen in patient outcomes.\n Except for two aspects, intensive small group education and peer review in asthma and COPD care do not seem to be effective in changing relevant aspects of the provided care by GPs in accordance with guidelines, nor in changing patients' health status.", "Great emphasis is placed on educating asthmatics to use action plans to achieve better control of symptoms. The use of peak flow meters (PFM) has been recommended as an important part of self-management plans. We studied 92 (47 F) adult patients with asthma in a primary care setting to compare the effectiveness of action plans using either peak flow monitoring or symptoms to guide self-management. Each patient was instructed in the use of the action plan in the context of a 6-mo asthma education program taught by a nurse. Patients were already using inhaled corticosteroids or were newly prescribed corticosteroids by their family physician. Forty-four patients were randomized to the PFM group and 48 to the symptoms group. Spirometry, symptom scores, quality of life, medication use, and measures of health care utilization and morbidity (emergency department visits, hospitalizations, unscheduled doctor visits, and days lost from work or school) were recorded at baseline and throughout the study period. PC20 methacholine was measured at the first and at the final visits. There were significant improvements within groups for FEV1, symptoms score, PC20 methacholine, and quality of life, but no between-group differences. A significant shift from higher to lower daily use of beta-agonists (p < 0.008 for both groups) and significant shifts to higher daily doses of inhaled steroids (p < 0.001) occurred in each group. Adherence to the self-management plans was only 65% in the PFM group and 52% in the symptoms group. Outcomes for health care utilization were similar except for fewer patients making unscheduled doctor visits within the PFM group. Our findings show that education, regular follow-up, and an action plan are effective in improving asthma control and quality of life, but the routine use of PFM to guide interventions is not the only way to accomplish these objectives.", "Asthma is common and is often poorly controlled in adolescent subjects.\n To determine the impact of an age-specific asthma program on asthma control, particularly on exacerbations of asthma requiring emergency department treatment, and on the quality of life of adolescents with asthma.\n The present randomized, controlled trial included patients who were 15 to 20 years of age and had visited emergency departments for management of their asthma. The interventional group attended an age-specific asthma program that included assessment, education and management by a team of asthma educators, respiratory therapists and respiratory physicians. In the control group, spirometry was performed, and the patients continued to receive usual care from their regular physicians. The outcomes were assessed by a questionnaire six months after entry into the study.\n Ninety-three subjects entered the study and were randomly assigned to the intervention or control group. Of these, only 62 patients were available for review after six months. Subjects in both the control and the intervention groups showed a marked improvement in their level of asthma control, reflected primarily by a 73% reduction in the rate of emergency department attendance for asthma. Other indexes of disease control, including disease-specific quality of life, as assessed by questionnaires, were improved. There was, however, no discernible difference between the subjects in the two groups, with the exception of an improvement in favour of the intervention group in the symptom (actual difference 0.7, P=0.048) and emotional (actual difference 0.8, P=0.028) domains of the asthma quality of life questionnaire. The overall quality of life score favoured the intervention group by a clinically relevant difference of 0.6, but this difference did not reach statistical significance (P=0.06).\n Although all subjects demonstrated a significant improvement in asthma control and quality of life, the improvement attributable to this intervention was limited to two domains in disease-specific quality of life.", "To test the ability of an automated telephone outreach intervention to reduce acute healthcare utilization and improve quality of life among adult asthma patients in a large managed care organization.\n Randomized clinical trial.\n Patients with persistent asthma were randomly assigned to telephone outreach (automated = 3389, live caller = 192) or usual care (n = 3367). Intervention participants received 3 outreach calls over a 10-month period. The intervention provided brief, supportive information and flagged individuals with poor asthma control for follow-up by a provider. A survey was mailed to 792 intervention participants and 236 providers after the intervention. Additional feedback was obtained as part of the final intervention contact.\n The intent-to-treat analysis found no significant differences between the intervention and usual-care groups for medication use, healthcare utilization, asthma control, or quality of life. Post hoc analyses found that, compared with the control group, individuals who actually participated in the intervention were significantly more likely to use inhaled steroids and to have had a routine medical visit for asthma during the follow-up period and less likely to use short-acting beta-agonists. They also reported higher satisfaction with their asthma care and better asthma-specific quality of life. Of surveyed providers, 59% stated the program helped them to clinically manage their asthma patients and 70% thought the program should be continued.\n This study did not find improved health outcomes in the primary analyses. The intervention was well accepted by providers, however, and the individuals who participated in the calls appeared to have benefited from them. These findings suggest that further studies of automated telephone outreach interventions seem warranted.", "Few robust studies have tested whether enhancing housing also improves health.\n To evaluate the effectiveness of installing ventilation systems, and central heating where necessary, in the homes of children with moderate or severe asthma.\n Pragmatic randomised controlled trial (RCT) in homes within Wrexham County Borough, Wales, UK.\n A pragmatic RCT was carried out, of a tailored package of housing improvements providing adequate ventilation and temperature, following inspection by a housing officer. One hundred and ninety-two children with asthma aged 5 to 14 years, identified from general practice registers, were randomised to receive this package, either immediately or a year after recruitment. At baseline, and after 4 and 12 months, parents reported their child's asthma-specific and generic quality of life, and days off school.\n The package improved parent-reported asthma-specific quality of life significantly at both 4 and 12 months. At 12 months, this showed an adjusted mean difference between groups of 7.1 points (95% confidence interval [CI] = 2.8 to 11.4, P= 0.001): a moderate standardised effect size of 0.42. The generic quality-of-life scale showed reported physical problems were significantly reduced at 4 months, but not quite at 12 months, when the mean difference was 4.5 (95% CI = -0.2 to 9.1, P= 0.061). The improvement in psychosocial quality of life at 12 months was not significant, with a mean difference of 2.2 (95% CI = -1.9 to 6.4, P= 0.292). Parent-reported school attendance improved, but not significantly.\n This novel and pragmatic trial, with integrated economic evaluation, found that tailored improvement of the housing of children with moderate to severe asthma significantly increases parent-reported asthma-related quality of life and reduces physical problems. Collaborative housing initiatives have potential to improve health.", "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.", "To determine whether locally developed guidelines on asthma and diabetes disseminated through practice based education improve quality of care in non-training, inner city general practices.\n Randomised controlled trial with each practice receiving one set of guidelines but providing data on the management of both conditions.\n 24 inner city, non-training general practices.\n East London.\n Recording of key variables in patient records (asthma: peak flow rate, review of inhaler technique, review of asthma symptoms, prophylaxis, occupation, and smoking habit; diabetes: blood glucose concentration, glycaemic control, funduscopy, feet examination, weight, and smoking habit); size of practice disease registers; prescribing in asthma; and use of structured consultation \"prompts.\"\n In practices receiving diabetes guidelines, significant improvements in recording were seen for all seven diabetes variables. Both groups of practices showed improved recording of review of inhaler technique, smoking habit, and review of asthma symptoms. In practices receiving asthma guidelines, further improvement was seen only in recording of review of inhaler technique and quality of prescribing in asthma. Sizes of disease registers were unchanged. The use of structured prompts was associated with improved recording of four of seven variables on diabetes and all six variables on asthma.\n Local guidelines disseminated via practice based education improve the management of diabetes and possibly of asthma in inner city, non-training practices. The use of simple prompts may enhance this improvement." ]

[ "10520389", "8630203", "15573192", "11956540", "12670818", "7598849", "9661546", "8895262", "8233511" ]

[ "The effect of single dose intravenous dexamethasone in tonsillectomy in children.", "The effect of intravenous dexamethasone in pediatric adenotonsillectomy.", "Use of dexamethasone to reduce postoperative vomiting and pain after pediatric tonsillectomy procedures.", "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 effect of preoperative dexamethasone on the immediate and delayed postoperative morbidity in children undergoing adenotonsillectomy.", "Dexamethasone decreases vomiting by children after tonsillectomy.", "The effects of preoperative steroids on tonsillectomy patients." ]

[ "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.", "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.", "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.", "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.", "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.", "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.", "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." ]

[ "16527165", "15630469", "14668455", "20415574", "17786128", "12441803", "18094377", "10755536", "18977721" ]

[ "[Clinical trial comparing efficacy and safety of four highly active antiretroviral therapy (HAART) in antiretroviral-naive treatment with advanced HIV infection].", "Randomized, controlled trial of therapy interruption in chronic HIV-1 infection.", "Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection.", "Early versus delayed initiation of antiretroviral therapy for concurrent HIV infection and cryptococcal meningitis in sub-saharan Africa.", "A randomized controlled trial of therapeutic drug monitoring in treatment-naive and -experienced HIV-1-infected patients.", "PharmAdapt: a randomized prospective study to evaluate the benefit of therapeutic monitoring of protease inhibitors: 12 week results.", "Reduced exposure to calcineurin inhibitors in renal transplantation.", "Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation.", "Virologic, immunologic, clinical, safety, and resistance outcomes from a long-term comparison of efavirenz-based versus nevirapine-based antiretroviral regimens as initial therapy in HIV-1-infected persons." ]

[ "Comparison of efficacy and safety of four highly active antiretroviral therapy regimens (HAART) including two nucleoside analogues (NA) and a protease inhibitor (PI) in HIV positive patients with advanced infection and antiretroviral naive.\n Multicenter, randomized and open labeled clinical trial in ten community hospitals of Castilla-La Mancha and Madrid. Regimen 1 contains zidovudine (AZT), lamivudine (3TC) and indinavir (IDV) regimen 2 includes AZT, 3TC and ritonavir (RTV), regimen 3 was didanosine (DDI), estavudine (D4T) and IDV, and regimen 4 included DDI, D4T and RTV. Decrease in viral load of HIV (VC) has been assessed as primary endpoint and as secondary one, the increase of the numbers of CD4 lymphocytes, percentage of disease progression, adverse reactions and adherence. Measurements were made at baseline visit and at 6, 12, 24, 36 and 48 weeks.\n A total of 98 patients with a mean baseline CD4 count of 122 x 10(6)/l (range of 5-340) and a baseline viral load of 5.1 log copies/ml were included. At 48 weeks, a mean increase of the CD4 and decrease of the viral load without significant difference between the 4 regimens (103 cells/2.62 log in regimen 1; 169 cells/2.86 log in regimen 2; 171 cells/2.56 log in regimen 3 and 141 cells/1.71 log in regimen 4) were observed in the analysis of the patients in treatment. Treatment was discontinued due to adverse reactions: 24% in regimen 1, 48% in regimen 2, 26% in regimen 3 and 32% in regimen 4, without significant difference. Analyzing by PI groups, 41% of the patients with RTV and 25% of those with IDV discontinued treatment due to adverse effects. There was withdrawal from treatment due to disease progression in 7% of the RTV patients and in 9% of IDV patients.\n In the HIV positive patients with advanced infection, efficacy between the four regimens of HAART is similar, but there is a tendency to require more withdrawal due to adverse effects in the RTV group than in those of IDV, the two used as single PI.", "Approaches to limiting exposure to antiretroviral therapy (ART) drugs are an active area of HIV therapy research. Here we present longitudinal follow-up of a randomized, open-label, single-center study of the immune, viral, and safety outcomes of structured therapy interruptions (TIs) in patients with chronically suppressed HIV-1 infection as compared to equal follow-up of patients on continuous therapy and including a final therapy interruption in both arms.\n Forty-two chronically HIV-infected patients on suppressive ART with CD4 counts higher than 400 were randomized 1:1 to either (1) three successive fixed TIs of 2, 4, and 6 wk, with intervening resumption of therapy with resuppression for 4 wk before subsequent interruption, or (2) 40 wk of continuous therapy, with a final open-ended TI in both treatment groups. Main outcome was analysis of the time to viral rebound (>5,000 copies/ml) during the open-ended TI. Secondary outcomes included study-defined safety criteria, viral resistance, therapy failure, and retention of immune reconstitution. There was no difference between the groups in time to viral rebound during the open-ended TI (continuous therapy/single TI, median [interquartile range] = 4 [1-8] wk, n = 21; repeated TI, median [interquartile range] = 5 [4-8] wk, n = 21; p = 0.36). No differences in study-related adverse events, viral set point at 12 or 20 wk of open-ended interruption, viral resistance or therapy failure, retention of CD4 T cell numbers on ART, or retention of lymphoproliferative recall antigen responses were noted between groups. Importantly, resistance detected shortly after initial viremia following the open-ended TI did not result in a lack of resuppression to less than 50 copies/ml after reinitiation of the same drug regimen.\n Cycles of 2- to 6-wk time-fixed TIs in patients with suppressed HIV infection failed to confer a clinically significant benefit with regard to viral suppression off ART. Also, secondary analysis showed no difference between the two strategies in terms of safety, retention of immune reconstitution, and clinical therapy failure. Based on these findings, we suggest that further clinical research on the long-term consequences of TI strategies to decrease drug exposure is warranted.", "The optimal sequencing of antiretroviral regimens for the treatment of infection with human immunodeficiency virus type 1 (HIV-1) is unknown. We compared several different antiretroviral treatment strategies.\n This multicenter, randomized, partially double-blind trial used a factorial design to compare pairs of sequential three-drug regimens, starting with a regimen including zidovudine and lamivudine or a regimen including didanosine and stavudine in combination with either nelfinavir or efavirenz. The primary end point was the length of time to the failure of the second three-drug regimen.\n A total of 620 subjects who had not previously received antiretroviral therapy were followed for a median of 2.3 years. Starting with a three-drug regimen containing efavirenz combined with zidovudine and lamivudine (but not efavirenz combined with didanosine and stavudine) appeared to delay the failure of the second regimen, as compared with starting with a regimen containing nelfinavir (hazard ratio for failure of the second regimen, 0.71; 95 percent confidence interval, 0.48 to 1.06), as well as to delay the second virologic failure (hazard ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09), and significantly delayed the failure of the first regimen (hazard ratio, 0.39) and the first virologic failure (hazard ratio, 0.34). Starting with zidovudine and lamivudine combined with efavirenz (but not zidovudine and lamivudine combined with nelfinavir) appeared to delay the failure of the second regimen, as compared with starting with didanosine and stavudine (hazard ratio, 0.68), and significantly delayed both the first and the second virologic failures (hazard ratio for the first virologic failure, 0.39; hazard ratio for the second virologic failure, 0.47), as well as the failure of the first regimen (hazard ratio, 0.35). The initial use of zidovudine, lamivudine, and efavirenz resulted in a shorter time to viral suppression.\n The efficacy of antiretroviral drugs depends on how they are combined. The combination of zidovudine, lamivudine, and efavirenz is superior to the other antiretroviral regimens used as initial therapy in this study.\n Copyright 2003 Massachusetts Medical Society", "BACKGROUND. Cryptococcal meningitis (CM) remains a leading cause of acquired immunodeficiency syndrome-related death in sub-Saharan Africa. The timing of the initiation of antiretroviral therapy (ART) for human immunodeficiency virus (HIV)-associated CM remains uncertain. The study aimed to determine the optimal timing for initiation of ART in HIV-positive individuals with CM. METHODS. A prospective, open-label, randomized clinical trial was conducted at a tertiary teaching hospital in Zimbabwe. Participants were aged > or = 18 years, were ART naive, had received a first CM diagnosis, and were randomized to receive early ART (within 72 h after CM diagnosis) or delayed ART (after 10 weeks of treatment with fluconazole alone). Participants received 800 mg of fluconazole per day. The ART regimen used was stavudine, lamivudine, and nevirapine given twice daily. The duration of follow-up was up to 3 years. The primary end point was all-cause mortality. RESULTS. Fifty-four participants were enrolled in the study (28 in the early ART arm and 26 in the delayed ART arm). The median CD4 cell count at enrollment was 37 cells/mm(3) (interquartile range, 17-69 cells/mm(3)). The 3-year mortality rate differed significantly between the early and delayed ART groups (88% vs 54%; P < .006); the overall 3-year mortality rate was 73%. The median durations of survival were 28 days and 637 days in the early and delayed ART groups, respectively (P = .031, by log-rank test). The risk of mortality was almost 3 times as great in the early ART group versus the delayed ART group (adjusted hazard ratio, 2.85; 95% confidence interval, 1.1-7.23). The study was terminated early by the data safety monitoring committee. CONCLUSIONS. In resource-limited settings where CM management may be suboptimal, when compared with a delay of 10 weeks after a CM diagnosis, early initiation of ART results in increased mortality. Trial registration. ClinicalTrials.gov identifier: NCT00830856.", "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.", "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", "Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens.\n We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival.\n The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than in those receiving standard-dose cyclosporine (25.8%), low-dose cyclosporine (24.0%), or low-dose sirolimus (37.2%). Allograft survival differed significantly among the four groups (P=0.02) and was highest in the low-dose tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%), the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group (89.3%). Serious adverse events were more common in the low-dose sirolimus group than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (86.3 to 90.5%).\n A regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction. (ClinicalTrials.gov number, NCT00231764 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.", "Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation.\n A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year.\n There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups.\n All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.", "To compare long-term virologic, immunologic, and clinical outcomes in antiretroviral-naïve persons starting efavirenz (EFV)- versus nevirapine (NVP)-based regimens.\n The FIRST study randomized patients into three strategy arms: PI+NRTI, NNRTI+NRTI, and PI+NNRTI+NRTI. NNRTI was determined by optional randomization (NVP or EFV) or by choice. For this randomized substudy, the primary endpoint was HIV RNA >50 copies/mL after 8 months or death. Genotypic resistance testing was done at virologic failure (VF; HIV RNA >1,000 copies/mL at or after 4 months).\n 228 persons (111 randomized to EFV, 117 to NVP) were followed for median 5 years. Rates per 100 person years for the primary endpoint were 41.2 (EFV) and 42.8 (NVP; p = .59). The percent of persons with HIV RNA <50 copies/mL was similar throughout follow-up (p = .24), as were average increases in CD4+ cells (p = .30). 423 persons declining the substudy chose EFV; 264 chose NVP. There were 915 persons in the combined cohort (randomized and choice). In the combined cohort, the risk of VF and VF with any NNRTI or NRTI resistance or resistance of any class was significantly less for EFV compared to NVP.\n EFV-based regimens as initial therapy resulted in a lower risk of VF and VF with resistance than did NVP-based regimens, although immunologic and clinical outcomes were similar." ]

[ "14553868", "16708309", "10600085", "2810183", "16998208", "15297305", "3296163", "15128726", "1889273" ]

[ "Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: a randomized controlled trial.", "Communication training and antibiotic use in acute respiratory tract infections. A cluster randomised controlled trial in general practice.", "A randomized, prospective study measuring outcomes after antibiotic therapy intervention by a multidisciplinary consult team.", "Comparison of two prophylactic single-dose intravenous antibiotic regimes in the treatment of patients undergoing elective colorectal surgery in a district general hospital.", "Improving empirical antibiotic treatment using TREAT, a computerized decision support system: cluster randomized trial.", "Effectiveness of a multiple intervention to reduce antibiotic prescribing for respiratory tract symptoms in primary care: randomised controlled trial.", "[Preventive preoperative antibiotic therapy in elective colon surgery. A controlled prospective randomized study].", "Improving appropriateness of antibiotic therapy: randomized trial of an intervention to foster reassessment of prescription after 3 days.", "Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen." ]

[ "Patients with pneumonia often remain hospitalized after they are stable clinically, and the duration of intravenous antibiotic therapy is a rate-limiting step for discharge. The purpose of this study was to determine whether implementation of an evidence-based guideline would reduce the duration of intravenous antibiotic therapy and length of stay for patients hospitalized with pneumonia.\n In a seven-site, cluster randomized clinical trial, we enrolled 325 control and 283 intervention patients who were admitted by one of 116 physician groups. Within site, physician groups were assigned randomly to receive a practice guideline alone (control arm) or a practice guideline that was implemented using a multifaceted strategy (intervention arm). The effectiveness of guideline implementation was measured by the duration of intravenous antibiotic therapy and length of stay; differences in the rates of discontinuation and hospital discharge were assessed with proportional hazards models. Medical outcomes were assessed at 30 days.\n Intravenous antibiotic therapy was discontinued somewhat more quickly in the intervention group (hazard ratio [HR] =1.23; 95% confidence interval [CI]: 1.00 to 1.52; P = 0.06) than in the control group. Intervention patients were discharged more quickly, but the difference was not statistically significant (HR = 1.16; 95% CI: 0.97 to 1.38; P = 0.11). Fewer intervention (55% [157/283]) than control (63% [206/325]) patients had medical complications during the index hospitalization (P = 0.04), with no differences in other medical outcomes, including mortality, rehospitalization, and return to usual activities, between treatment arms.\n The multifaceted guideline implementation strategy resulted in a slight reduction in the duration of intravenous antibiotic therapy and a nonsignificant reduction in length of stay, without affecting patient outcomes.", "A cluster-randomised controlled trial in general practice\n Physician-patient communication plays a key role in treatment decisions in primary care. We aimed to reduce the antibiotic prescription rate for acute respiratory tract infections using a short training programme in patient-centred communication.\n We conducted a cluster-randomised controlled trial in 45 general practices in Switzerland. Thirty physicians received evidence-based guidelines for the management of acute respiratory tract infections; 15 physicians randomised to the full intervention additionally received training in patient-centred communication. A further 15 physicians, not randomised, served as a control to blind the physicians in the other two groups to the true comparison. The primary outcome was the antibiotic prescription rate reported by pharmacists. Secondary outcomes were patient satisfaction and enablement, re-consultation rates, days with restrictions, and days off work. 1108 adults with acute respiratory infections were screened between January and May 2004. Outcomes were measured in 837 consultations; 624 patients had follow-up interviews at 7 and 14 days.\n The antibiotic prescription rate reported by pharmacists was low in both full and limited intervention groups (13.5% and 15.7% respectively) but only half of the antibiotics were prescribed according to guidelines (53.8% and 53.1%). No significant differences were seen between the two randomised groups in primary and secondary outcomes. In both groups patient satisfaction was high (median score for both 68 out of 70).\n In this trial, patient-centred communication training did not reduce the rate of antibiotic prescriptions below an already unusually low level. Even with this low prescription rate, patient satisfaction with received care was high.", "Our aim was to identify financial and outcome benefits of therapeutic intervention by a multidisciplinary antimicrobial treatment team composed of pharmacists, a clinical microbiologist, and an infectious disease specialist. Of 252 consecutive inpatients receiving suboptimal intravenous antibiotics identified by the clinical pharmacist, 127 were prospectively randomized to intervention and 125 to a control group. The groups were similar with regard to severity of illness, infection type, and time from admission to randomization. Physicians received timely, detailed reviews of relevant microbiologic and clinical data with recommendations of possible optimal antibiotic choices, dosages, and rationales. Median length of stay after randomization for control and intervention groups was 9.0 days and 5.7 days, respectively (3.3-day difference, p=0.0001). Fifteen (12.0%) and eight patients (6.3%), respectively, died, although the time-specific mortality risk was not significantly different when length of postrandomization follow-up and time to death were taken into account. Physician acceptance of suggestions was 89%. Median patient charges for radiology, laboratory, pharmacy, and room were reduced by $4404/intervention, and median hospital costs were reduced by $2642/intervention. A multidisciplinary antimicrobial therapy team can be a useful information source for physicians, improve outcomes in hospitalized patients receiving intravenous antimicrobials, and result in substantial cost savings.", "Two hundred and twenty-nine patients were entered into a study to compare the effectiveness and safety of two single-shot antibiotic regimes in patients undergoing elective colorectal surgery in two district general hospitals. A single shot of intravenous (IV) latamoxef disodium was as effective as an IV combination of cefuroxime and metronidazole in control of wound infection following elective large bowel surgery when given as a bolus at the time of anaesthetic induction. The incidence of major wound infection was 6% and was evenly distributed in the two treatment groups. Half the major wound infections were associated with faecal fistulae. A single shot of IV antibiotic at the time of anaesthetic induction was safe, simple and an effective prophylaxis against major wound infection. There was a low incidence (1.3%) of serious postoperative bleeding and no serious adverse reactions were noted. The overall mortality was 9%. Death was significantly related to elderly patients, a poor performance status, operative contamination and wound infections.", "Appropriate antibiotic treatment decreases mortality, while superfluous treatment is associated with antibiotic resistance. We built a computerized decision support system for antibiotic treatment (TREAT) targeting these outcomes.\n Prospective cohort study comparing TREAT's advice to physician's treatment followed by a cluster randomized trial comparing wards using TREAT (intervention) versus antibiotic monitoring without TREAT (control). We included patients suspected of harbouring bacterial infections in three hospitals (Israel, Germany and Italy). The primary outcome, appropriate antibiotic treatment, was assessed among patients with microbiologically documented infections (MDI). Length of hospital stay, adverse events, mortality (interventional trial) and antibiotic costs (both studies), including costs related to future antibiotic resistance, were compared among all included patients.\n Among 1203 patients included in the cohort study (350 with MDI), TREAT prescribed appropriate empirical antibiotic treatment significantly more frequently than physicians (70% versus 57%, P < 0.001) using less broad-spectrum antibiotics at half physicians' antibiotic costs. The randomized trial included 2326 patients, 570 with MDI. The rate of appropriate empirical antibiotic treatment was higher in intervention versus control wards [73% versus 64%, odds ratio (OR): 1.48, 95% confidence interval (CI): 0.95-2.29, intention to treat, adjusted for location and clustering]. For patients treated according to TREAT's advice in intervention wards, the difference with controls was highly significant (OR: 3.40, 95% CI: 2.25-5.14). Length of hospital stay, costs related to future resistance and total antibiotic costs were lower in intervention versus control wards.\n TREAT improved the rate of appropriate empirical antibiotic treatment while reducing antibiotic costs and the use of broad-spectrum antibiotic treatment.", "To assess the effectiveness of a multiple intervention aimed at reducing antibiotic prescription rates for symptoms of the respiratory tract in primary care.\n Randomised controlled trial.\n Twelve peer review groups including 100 general practitioners with their collaborating pharmacists in the region of Utrecht, Netherlands.\n The intervention consisted of group education meetings, with a consensus procedure on indication for and type of antibiotics and with training in communication skills; monitoring and feedback on prescribing behaviour; group education for assistants of general practitioners and pharmacists; and education material for patients. The control group did not receive any of these elements.\n Antibiotic prescription rates for acute symptoms of the respiratory tract and patients' satisfaction.\n 89 general practitioners completed the study (89%). At baseline, prescription rates for antibiotics for respiratory tract symptoms did not differ between intervention and control group (27% v 29%, respectively). After nine months, the prescription rates in the intervention group fell to 23%, whereas the control group's rose to 37% (mean difference in change -12%, 95% confidence interval -18.9% to -4.0%). Multilevel analysis confirmed the results of the unadjusted analysis (intervention effect -10.7%, -20.3% to -1.0%). Patients' satisfaction was high and did not differ in the two groups at baseline or after the intervention.\n A multiple intervention reduced prescribing rates of antibiotics for respiratory tract symptoms while maintaining a high degree of satisfaction among patients. Further research should focus on the sustainability and cost effectiveness of this intervention.", "Antibiotic prophylaxis in elective colonic surgery is of established value and most authors have proposed an association of at least two drugs. We have compared the efficacy of classical prophylaxis (clindamycin and gentamicin, C + G) with that of the single drug cefoxitin (Ce). 101 consecutive patients were covered; 22 had to be excluded and 7 withdrawn after randomization; 72 cases were left for final analysis (C + G 35; Ce 37). Five C + G (14.2%) and 4 Ce cases (10.8%) developed septic complications, possibly caused by opening of the colon (wound infection, anastomotic failure, colocutaneous fistula): this difference is not statistically significant. Episodes of sepsis, urinary tract infection and pneumonia were similar in both groups. Although the number of patients included is relatively small, we conclude that prophylaxis with Ce alone appears to be as effective as double drug prophylaxis with C + G.", "Reassessment of ongoing antibiotic therapy is an important step towards appropriate use of antibiotics. This study was conducted to evaluate the impact of a short questionnaire designed to encourage reassessment of intravenous antibiotic therapy after 3 days.\n Patients hospitalized on the surgical and medical wards of a university hospital and treated with an intravenous antibiotic for 3-4 days were randomly allocated to either an intervention or control group. The intervention consisted of mailing to the physician in charge of the patient a three-item questionnaire referring to possible adaptation of the antibiotic therapy. The primary outcome was the time elapsed from randomization until a first modification of the initial intravenous antibiotic therapy. It was compared within both groups using Cox proportional-hazard modelling.\n One hundred and twenty-six eligible patients were randomized in the intervention group and 125 in the control group. Time to modification of intravenous antibiotic therapy was 14% shorter in the intervention group (adjusted hazard ratio for modification 1.28, 95% CI 0.99-1.67, P = 0.06). It was significantly shorter in the intervention group compared with a similar group of 151 patients observed during a 2 month period preceding the study (adjusted hazard ratio 1.17, 95% CI 1.03-1.32, P = 0.02).\n The results suggest that a short questionnaire, easily adaptable to automatization, has the potential to foster reassessment of antibiotic therapy.", "The objective of this study was to assess the effect of a novel regimen of antibiotic prophylaxis on the incidence of lower respiratory tract infection in patients requiring prolonged (at least five days) mechanical ventilation. The design was a controlled, prospective, randomized trial, with blinded comparison of the groups regarding the incidence of respiratory tract infection in an intensive care unit of a university hospital. After determination of the APACHE II score for severity of disease, 88 patients were randomly divided in three groups. Twenty-four of these patients did not complete five days of mechanical ventilation, and eight were withdrawn for other reasons. Fifty-six patients (18 in group 1, 21 in group 2, 17 in group 3) completed the study. Patients in both control groups 1 and 2 did not receive antibiotic prophylaxis, but the two groups differed in the antibiotic policy in case of infection. Patients in group 3 received antibiotic prophylaxis consisting of norfloxacin, polymyxin E, and amphotericin B, applied topically in oropharynx and stomach from time of ICU admission until extubation, and intravenous cefotaxime 500 mg three times a day during the first five days of admission. In both control groups, about 90 percent of the patients acquired microbial colonization of oropharynx or stomach. In group 3, only 12 percent and 24 percent of the patients acquired colonization of oropharynx and stomach, respectively (p less than 0.001). This resulted in a reduction of the incidence of lower respiratory tract infection (78 percent in group 1, 62 percent in group 2, 6 percent in group 3 [p = 0.0001]). The regimen of antibiotic prophylaxis studied prevented respiratory tract infection in mechanically ventilated patients. Antibiotic prophylaxis should be considered in all patients expected to require prolonged mechanical ventilation." ]

[ "16531614", "16531613", "14762035", "18714059", "20571015", "20688574", "18206891", "14535967", "10095804" ]

[ "Homocysteine lowering and cardiovascular events after acute myocardial infarction.", "Homocysteine lowering with folic acid and B vitamins in vascular disease.", "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.", "Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled 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.", "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.", "Effect of homocysteine-lowering therapy on arterial elasticity and metabolic parameters in metformin-treated diabetic patients.", "Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial.", "Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment." ]

[ "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.", "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.", "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.", "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.", "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.", "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.", "Metformin may affect the risk of atherothrombotic disease. However, metformin increases levels of homocysteine (Hcy), considered an independent risk factor for atherosclerosis. We evaluate whether homocysteine-lowering has a beneficial effect on arterial elasticity and metabolic parameters in metformin-treated diabetic patients. In double-blind, placebo-controlled study, 60 diabetic patients treated with high dose of metformin were randomly assigned to receive daily oral supplementation with folate (1000 mcg), vitamins B12 (400 mcg) and B6 (10mg) (group 1) or placebo (group 2). Lipid profile, HbA1C, insulin, C-peptide, hs-CRP, vitamin B12, folic acid, homocysteine, endothelin, homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, MN). The two groups were similar at baseline in terms of hemodynamic and arterial elasticity parameters. After a 4-month small artery elasticity index (SAEI) was significantly greater in patients who received Hcy-lowering agents than in the placebo group: 4.3+/-2.04 ml/mm Hg x 100 versus 3.2+/-1.1 ml/mm Hg x 100, p=0.01. Post-treatment vitamin B12 and folic acid levels were greater in group 1 versus group 2: 738.1+/-279.9 pg/ml versus 566.1+/-167.4 pg/ml, p=0.007 and 14.9+/-4.8 ng/ml versus 8.3+/-2.9 ng/ml, p<0.0001, respectively. Hcy level decreased significantly in the treatment group from 10.0+/-4.4 to 7.6+/-2.5 micromol/l, p=0.002 and did not change in placebo group (p=0.9). Hcy-lowering therapy improved small arterial elasticity in diabetic patients treated with high dose of metformin. The improvement was associated with a decrease in Hcy as well as an increase in folic acid and vitamin B12. These findings suggest that Hcy-lowering may have beneficial vascular effect in metformin-treated diabetic patients.", "Metformin is a key treatment option in type 2 diabetes. However, metformin may decrease vitamin B12 levels and increase levels of homocysteine, a cardiovascular risk factor. We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homocysteine, folate and vitamin B12 in subjects with type 2 diabetes treated with insulin.\n Placebo-controlled, randomized trial. Measurements: at baseline and 16 weeks later.\n This trial was conducted in the outpatient clinics of three general hospitals in The Netherlands.\n A total of 745 patients with type 2 diabetes, treated with insulin and not known with a contraindication for the use of metformin, were approached; 390 gave informed consent and entered the study. Thirty-seven subjects dropped out (12 placebo and 25 metformin users).\n Addition of metformin or placebo to insulin therapy. PRIMARY OUTCOME PARAMETERS: Serum homocysteine, folate, vitamin B12, indices of glycaemic control and body weight.\n Amongst those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with an increase in homocysteine of 4% (0.2 to 8; P=0.039) and with decreases in folate [-7% (-1.4 to -13); P=0.024] and vitamin B12 [-14% (-4.2 to -24); P<0.0001]. In addition, the increase in homocysteine could be explained by the decreases in folate and vitamin B12.\n In patients with type 2 diabetes, 16 weeks of treatment with metformin reduces levels of folate and vitamin B12, which results in a modest increase in homocysteine. The clinical significance of these findings remains to be investigated.", "Metformin treatment increases circulating homocysteine levels. We studied whether administration of folate reduces serum total homocysteine levels in patients on long-term metformin treatment.\n A prospective, randomized, double-blind, placebo-controlled study lasting for 12 weeks and taking place in a university hospital setting.\n Thirty patients treated with a metformin dose of at least 1000 mg day-1 for a minimum of 1 year were included. At baseline serum total homocysteine levels were within the reference range. One patient who withdrew and one who died were excluded from the statistical evaluation. Twenty-six of the remaining patients suffered from NIDDM, the other two from hyperlipidaemia.\n Patients were randomized into two groups at week 0. The folate group received 0.25 mg day-1 of folate in addition to 60 mg day-1 of Fe2+, while the placebo group received only 60 mg day-1 of Fe2+.\n Fasting homocysteine, cysteine, cysteinylglycine, vitamin B12 and folate were measured at week 0, 4 and 12. Changes from week 0 to week 4 and from week 0 to week 12 were calculated.\n Folate administration reduced serum levels of total homocysteine in the folate group as compared with the placebo group by 13.9% (P < 0.01) and 21.7% (P < 0.001) at week 4 and 12, respectively. In the folate group versus the placebo group serum levels of vitamin B12 increased by 9.9% (P = 0.010) and 9.6% (P = 0.043) while folate levels increased by 96.9 and 89.9% at week 4 and 12, respectively.\n The present study indicates that the homocysteine-increasing effect of metformin can be counteracted by folate administration." ]

[ "1773955", "17059514", "1905672", "8314510", "1679736", "10961730", "11336163", "10710067", "11871742" ]

[ "Controlled trial comparing two types of enteral nutrition in treatment of active Crohn's disease: elemental versus polymeric diet.", "Effectiveness of an 'half elemental diet' as maintenance therapy for Crohn's disease: A randomized-controlled trial.", "Enteral feeding as sole treatment for Crohn's disease: controlled trial of whole protein v amino acid based feed and a case study of dietary challenge.", "Polymeric enteral diets as primary treatment of active Crohn's disease: a prospective steroid controlled trial.", "Comparison of enteral nutrition and drug treatment in active Crohn's disease. Results of the European Cooperative Crohn's Disease Study. IV.", "Saccharomyces boulardii in maintenance treatment of Crohn's disease.", "Does adjuvant nutritional support diminish steroid dependency in Crohn disease?", "Polymeric versus elemental diet as primary treatment in active Crohn's disease: a randomized, double-blind trial.", "Short-term efficacy of enteral nutrition in the treatment of active Crohn's disease: a randomized, controlled trial comparing nutrient formulas." ]

[ "To determine whether an elemental diet or a polymeric defined formula diet would be more effective for treating active Crohn's disease, we conducted a prospective randomised clinical trial in 30 patients with active Crohn's disease unresponsive to steroids and/or complicated by malnutrition. They received a four to six week enteral nutrition course with either an elemental diet or a polymeric diet. Clinical remission occurred in 10 of the 15 patients on elemental diet compared with 11 of the 15 patients assigned to polymeric diet. Both groups showed similar improvements in nutritional status, biological inflammation, alpha 1 antitrypsin clearance, and colonoscopic lesions (diminished in 17 out of 24 patients). Most patients relapsed during the year after discharge. We conclude that enteral nutrition, whatever the diet, is an efficient primary therapy for active Crohn's disease but does not influence the long term outcome.", "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.", "A controlled trial was performed to compare enteral feeding with either an amino acid based feed or a whole protein feed as sole treatment for active Crohn's disease. Twenty four patients were studied (nine with ileal, 11 with ileocolonic, and four with colonic disease). Both feeds proved effective; nine of 13 patients randomised to receive the amino acid based feed were in clinical remission within three weeks as defined by a simple activity index compared with eight of 11 treated with the whole protein feed. Patients in clinical remission were then crossed over onto the other feed. None of the six patients who were changed to the whole protein feed relapsed over the subsequent three week period compared with three of seven patients who were changed to the amino acid based feed. In responders the median serum C reactive protein concentration fell from 21 mg/l (range 9-82) on entry to 6 mg/l (range 3-19) at six weeks. Seven patients relapsed within eight months of starting solid food (mean 3.7 months), while nine were still in remission (follow up period 3-9 months, median six months). Detailed studies of staged reintroduction of food and permitted food additives were carried out over a four year period in a patient with extensive stricturing small bowel Crohn's disease who had been brought into remission by open treatment with enteral feeding. Carrageenan, other permitted emulsifiers, bread, meat, potatoes, oranges, refined sugar, dairy produce, flour, and rice were all reintroduced without any objective ill effect, but green vegetables provoked a clinical and biochemical relapse within one week of introduction. Remission was rapidly achieved by switching back to the enteral feed but reintroduction of the low residue diet that had been previously tolerated produced a brisk relapse. Clinical and biochemical remission was again achieved by a return to the enteral feed but relapse again occurred with reintroduction of the low residue diet. These studies confirm the therapeutic effect of enteral feeding in Crohn's disease. This effect does not seem to be due to avoidance of whole protein, but the very low residue of chemically defined enteral feeds may be important, particularly in patients with intestinal strictures.", "Thirty two patients with active Crohn's disease were included in a controlled randomised trial to determine the efficacy and safety of polymeric enteral nutrition compared with steroids, to achieve and maintain clinical remission. The polymeric diet was administered through a fine bore nasogastric tube by continuous, pump assisted infusion (2800 (SEM 120) kcal/day). The steroid group received 1 mg/kg/day of prednisone. Both treatments were effective in inducing clinical remission: 15 of the 17 patients given steroids and 12 of the 15 patients assigned to the polymeric diet went into clinical remission (defined by a Van Hees index < 120) within four weeks of treatment. The percentage reduction of the Van Hees index was 34.8 (4.9)% for steroids and 32.3 (5)% for enteral nutrition (mean difference 2.5%; 95% CI--11.8% to +16.8%). Mean time elapsed to achieve remission was similar in both groups (2.0 (1) v 2.4 (1.2) weeks). Tolerance of the enteral diet was excellent. Four patients in the steroid group had mild complications attributable to this treatment. Ten patients (66.6%) in the steroid group and five (41.6%) in the enteral nutrition group relapsed within a year of discharge, but no differences were found in the cumulative probability of relapse during the follow up period. These results suggest that polymeric enteral nutrition is as safe and effective as steroids in inducing short term remission in active Crohn's disease.", "This study compared the effect of enteral nutrition as the sole therapy of active Crohn's disease with drug treatment. Patients with active Crohn's disease (Crohn's Disease Activity Index greater than 200) were randomized to receive either enteral nutrition with a liquid oligopeptide diet (n = 55) or a combination of 6-methylprednisolone, 48 mg daily, subsequently tapered, and sulfasalazine, 3 g daily (n = 52). The two groups were not different with respect to age, sex, body weight, location of disease, or treatment before the study. The severity of disease was similar at the beginning of the study in both groups [Crohn's Disease Activity Index (mean +/- SEM), 323 +/- 12 vs. 316 +/- 11]. Remission was defined as a decrease of the initial Crohn's Disease Activity Index by 40% or at least 100 points. Twenty-nine patients in the diet group and 41 patients in the drug group reached remission within 6 weeks of therapy (chi 2 test, P less than 0.01). The median elapsed time to remission was 30.7 days in the diet group compared with 8.2 days in the drug group (Mantel Cox, P less than 0.01). To determine whether one of these treatments was more beneficial for a subgroup of patients, the effectiveness of both treatments was analyzed separately in patients with very severe disease (initial Crohn's Disease Activity Index greater than 300) and less severe disease (initial Crohn's Disease Activity Index less than 300), and in patients with different disease location. However, no influence of initial disease activity or disease location on the effect of either treatment could be shown. These data show that enteral nutrition is less effective than a combination of 6-methylprednisolone and sulfasalazine in treating active Crohn's disease.", "The possible role of Saccharomyces boulardii, a nonpathogenic yeast with beneficial effects on the human intestine, in the maintenance treatment of Crohn's disease has been evaluated. Thirty-two patients with Crohn's disease in clinical remission (CDAI < 150) were randomly treated for six months with either mesalamine 1 g three times a day or mesalamine 1 g two times a day plus a preparation of Saccharomyces boulardii 1 g daily. Clinical relapses as assessed by CDAI values were observed in 37.5% of patients receiving mesalamine alone and in 6.25% of patients in the group treated with mesalamine plus the probiotic agent. Our results suggest that Saccharomyces boulardii may represent a useful tool in the maintenance treatment of Crohn's disease. However, in view of the product's cost, further controlled studies are needed to confirm these preliminary data.", "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.", "Enteral feeding is now an established primary therapy for active Crohn's disease. This first-double blind randomized trial was designed to compare the therapeutic efficacy of a polymeric diet (PD) with an elemental diet (ED).\n Patients with active Crohn's disease (Crohn's disease activity index [CDAI] > 150, increased bowel uptake of Tc-HMPAO-labeled leukocytes, and abnormal C-reactive protein [CRP]), were randomized to receive either an ED or a PD. The two preparations were identical except for the nitrogen source, which was amino acid based in ED and intact protein in PD. Enteral feeding was considered successful if clinical remission was achieved as defined by a final CDAI of < or = 150, a reduction in the CDAI by at least 100 points from baseline level, and a normal CRP.\n Twenty-one patients were enrolled of whom 11 were randomized to PD and 10 to ED. The two groups were comparable at entry. Clinical remission was obtained in eight (80%) patients receiving ED and six (55%) patients receiving PD, p = 0.1. The treatment failed in three and two patients in the PD and ED groups, respectively. Another two patients were intolerant to the feed (PD). Reduction in the CDAI after treatment with ED (359 +/- 67 to 112 +/- 19) was similar to that seen with PD (303 +/- 27 to 97 +/- 11). Similar changes in the CRP were also observed (16 +/- 5 to 4 +/- 1.6) and (62 +/- 20 to 9 +/- 6), respectively. Overall, enteral feeding was successful in 14 patients (63%).\n Enteral nutrition is effective in treatment of active Crohn's disease. Differences in nitrogen sources of enteral feeds are not relevant to their therapeutic efficacy, as polymeric and elemental diets are equally effective.", "The optimal dietary fat content to induce clinical remission in active Crohn's disease has been the subject of controversy. We therefore performed a prospective, randomized, controlled study to compare the effects of nutrient formulas differing in the amount of medium-chain triglycerides (MCT).\n Thirty-six patients with active Crohn's disease whose Crohn's disease activity index (CDAI) was > or =150 were included in the study. A formula with 3.4 g of fat per 2000-kcal dose was used as the nutrient formula with a low-fat content (ED group), and a formula with 55.6 g of fat per 2000-kcal dose was used as the nutrient formula with a high amount of MCT (TL group).\n The rate of short-term remission induction at 6 weeks was 67% in the ED group and 72% in the TL group (p = NS). Therapy markedly reduced the high CDAI and van Hees activity index in both groups, with no significant difference in the pattern of the time-course changes. C-reactive protein levels, erythrocyte sedimentation rate, and low serum albumin and plasma prealbumin levels normalized over the course of therapy, with no significant difference between the 2 groups. The assessment of fatty acid fractions revealed that the triene/tetraene ratio began to increase at 2 weeks in the ED group. The serum levels of linoleic acid, an omega-6 fatty acid, almost always varied within the normal range during the treatment period in the TL group, but in the ED group, levels began to decrease significantly at 2 weeks. The levels of linolenic acid, an omega-3 fatty acid, decreased in both groups.\n Both nutrient formulas induced clinical remission in about two-thirds of patients. The results of the present study suggest that it is not necessary to restrict the amount of MCT when given in liquid form to patients with active Crohn's disease." ]

[ "10667738", "17166313", "19825502", "17530622", "19061735", "22324056", "12122183", "12425704", "16323385" ]

[ "Effects of cognitive treatment in psychiatric rehabilitation.", "Cognitive rehabilitation in the elderly: effects on strategic behavior in relation to goal management.", "Efficacy and specificity of intensive cognitive rehabilitation of attention and executive functions in multiple sclerosis.", "A randomized, two-year study of the efficacy of cognitive intervention on elderly people: the Donostia Longitudinal Study.", "A randomized controlled trial of holistic neuropsychologic rehabilitation after traumatic brain injury.", "Evaluation of rehabilitation of memory in neurological disabilities (ReMiND): a randomized controlled trial.", "Viewing less to see better.", "Effects of cognitive training interventions with older adults: a randomized controlled trial.", "Cognitive rehabilitation combined with drug treatment in Alzheimer's disease patients: a pilot study." ]

[ "Ninety subjects with severe and disabling psychiatric conditions, predominantly schizophrenia, participated in a controlled-outcome trial of the cognitive component of Integrated Psychological Therapy (IPT), a group-therapy modality intended to reestablish basic neurocognitive functions. The cognitive therapy was delivered to subjects in the experimental condition during intensive 6-month treatment periods. Control subjects received supportive group therapy. Before, during, and after the intensive treatment period, all subjects received an enriched regimen of comprehensive psychiatric rehabilitation, including social and living skills training, optimal pharmacotherapy, occupational therapy, and milieu-based behavioral treatment. IPT subjects showed incrementally greater gains compared with controls on the primary outcome measure, the Assessment of Interpersonal Problem-Solving Skills, suggesting that procedures that target cognitive impairments of schizophrenia spectrum disorders can enhance patients' response to standard psychiatric rehabilitation, at least in the short term, in the domain of social competence. There was equivocal evidence for greater improvement in the experimental condition on the Brief Psychiatric Rating Scale disorganization factor and strong evidence for greater improvement on a laboratory measure of attentional processing. There was significant improvement in both conditions on measures of attention, memory, and executive functioning, providing support for the hypothesis that therapeutic procedures that target impaired cognition enhance response to conventional psychiatric rehabilitation modalities over a 6-month timeframe.", "Executive functions are highly sensitive to the effects of aging and other conditions affecting frontal lobe function. Yet there are few validated interventions specifically designed to address executive functions, and, to our knowledge, none validated in a healthy aging sample. As part of a large-scale cognitive rehabilitation randomized trial in 49 healthy older adults, a modified Goal Management Training program was included to address the real-life deficits caused by executive dysfunction. This program emphasized periodic suspension of ongoing activity to establish goal hierarchies and monitor behavioral output. Tabletop simulated real-life tasks (SRLTs) were developed to measure the processes targeted by this intervention. Participants were randomized to two groups, one of which received the intervention immediately and the other of which was wait-listed prior to rehabilitation. Results indicated improvements in SRLT performance and self-rated executive deficits coinciding with the training in both groups. These gains were maintained at long-term follow-up. Future research will assess the specificity of these effects in patient groups.", "To evaluate the efficacy of a computer-based intensive training program of attention, information processing and executive functions in patients with clinically-stable relapsing-remitting (RR) multiple sclerosis (MS) and low levels of disability. DESIGN, PATIENTS AND INTERVENTIONS: A total of 150 patients with RR MS and an Expanded Disability Status Scale (EDSS) score of < or =4 were examined. Information processing, working memory and attention were assessed by the Paced Auditory Serial Addition Test (PASAT) and executive functions by the Wisconsin Card Sorting Test (WCST). Twenty patients who scored below certain cut-off measures in both tests were included in this double-blind controlled study. Patients were casually assigned to a study group (SG) or a control group (CG) and underwent neuropsychological evaluation at baseline and after 3 months. Patients in the SG received intensive computer-assisted cognitive rehabilitation of attention, information processing and executive functions for 3 months; the CG did not receive any rehabilitation.\n Ambulatory patients were sent by the MS referral center.\n Improvement in neuropsychological test and scale scores.\n After rehabilitation, only the SG significantly improved in tests of attention, information processing and executive functions (PASAT 3'' p=0.023, PASAT 2'' p=0.004, WCSTte p=0.037), as well as in depression scores (MADRS p=0.01). Neuropsychological improvement was unrelated to depression improvement in regression analysis.\n Intensive neuropsychological rehabilitation of attention, information processing and executive functions is effective in patients with RR MS and low levels of disability, and also leads to improvement in depression.", "Research on non-pharmacological therapies (cognitive rehabilitation) in old age has been very limited, and most has not considered the effect of interventions of this type over extended periods of time.\n To investigate a new cognitive therapy in a randomized study with elderly people who did not suffer cognitive impairment.\n The efficacy of this therapy was evaluated by means of post-hoc analysis of 238 people using biomedical, cognitive, behavioural, quality of life (QoL), subjective memory, and affective assessments.\n Scores for learning potential and different types of memory (working memory, immediate memory, logic memory) for the treatment group improved significantly relative to the untreated controls.\n The most significant finding in this study was that learning potential continued at enhanced levels in trained subjects over an intervention period lasting two years, thereby increasing rehabilitation potential and contributing to successful ageing.", "To evaluate the effectiveness of comprehensive, holistic neuropsychologic (NP) rehabilitation compared with standard, multidisciplinary rehabilitation for people with traumatic brain injury (TBI).\n Randomized practical controlled trial.\n Postacute brain injury rehabilitation center within a suburban rehabilitation hospital.\n Participants with TBI were recruited from clinical referrals and referrals from the community. Sixty-eight participants who met inclusion criteria were randomly allocated to treatment conditions. Most participants (88%) had sustained moderate or severe TBI, and greater than half (57%) were more than 1 year postinjury at the beginning of treatment.\n Treatment was conducted 15 hours per week for 16 weeks. Standard neurorehabilitation consisted primarily of individual, discipline specific therapies (n=34). Intensive cognitive rehabilitation emphasized the integration of cognitive, interpersonal, and functional interventions within a therapeutic environment (n=34).\n Primary outcomes were the Community Integration Questionnaire (CIQ) and Perceived Quality of Life scale (PQOL). Secondary outcomes included NP functioning, perceived self-efficacy, and community-based employment.\n NP functioning improved in both conditions. Intensive cognitive rehabilitation participants showed greater improvements on the CIQ (effect size [ES]=0.59) and PQOL (ES=0.30) as well as improved self-efficacy for the management of symptoms (ES=0.26) compared with standard neurorehabilitation treatment. These gains were maintained at the 6-month follow-up. Standard neurorehabilitation participants showed improved productivity at the 6-month follow-up associated with the need for continued rehabilitation.\n Improvements seen after intensive cognitive rehabilitation may be related to interventions directed at the self-regulation of cognitive and emotional processes and the integrated treatment of cognitive, interpersonal, and functional skills. The results show the effectiveness of comprehensive holistic NP rehabilitation for improving community functioning and quality of life after TBI compared with standard rehabilitation.", "The evidence for the effectiveness of memory rehabilitation is inconclusive. The aim was to compare the effectiveness of two group memory rehabilitation programmes with a self-help group control.\n Single-blind randomized controlled trial.\n Participants with memory problems following traumatic brain injury, stroke or multiple sclerosis were recruited from community settings.\n Participants were randomly allocated, in cohorts of four, to compensation or restitution group treatment programmes or a self-help group control. All programmes were manual-based and comprised two individual and ten weekly group sessions.\n Memory functions, mood, and activities of daily living were assessed at baseline and five and seven months after randomization.\n There were 72 participants (mean age 47.7, SD 10.2 years; 32 men). There was no significant effect of treatment on the Everyday Memory Questionnaire (P = 0.97). At seven months the mean scores were comparable (restitution 36.6, compensation 41.0, self-help 44.1). However, there was a significant difference between groups on the Internal Memory Aids Questionnaire (P = 0.002). The compensation and restitution groups each used significantly more internal memory aids than the self-help group (P < 0.01). There were no statistically significant differences between the groups on measures of mood, adjustment and activities of daily living (P > 0.05).\n There results show few statistically significant effects of either compensation or restitution memory group treatment as compared with a self-help group control. Further randomized trials of memory rehabilitation are needed.", "To assess the efficacy, as well as the long term duration, of a new procedure for the rehabilitation of visuospatial neglect in patients with right hemisphere stroke.\n Patients with right unilateral hemispheric damage identified with neglect were assigned to a treatment (T+) or a control (T-) group. The treatment consisted in abolishing all visual inputs from the right hemispace for one week by means of specially devised hemiblinding goggles. Patients' visuospatial abilities were tested and compared between groups immediately after the week of treatment. Both groups were further assessed one week after treatment suspension for evaluation of long term beneficial effects.\n Following the treatment, a substantial amelioration of visuospatial neglect symptoms was selectively observed in the T+ group. In contrast, untreated patients showed only weak signs of recovery. Most important, the amelioration obtained in the T+ group of patients was not ephemeral, being significantly maintained after a further period of one week, even after suspension of the treatment.\n The protracted efficacy of the proposed \"hemiblinding technique\" may have important implications for the recovery of visuospatial neglect and may be a very promising tool for investigating both the cognitive and the neural basis of neglect rehabilitation.", "Cognitive function in older adults is related to independent living and need for care. However, few studies have addressed whether improving cognitive functions might have short- or long-term effects on activities related to living independently.\n To evaluate whether 3 cognitive training interventions improve mental abilities and daily functioning in older, independent-living adults.\n Randomized, controlled, single-blind trial with recruitment conducted from March 1998 to October 1999 and 2-year follow-up through December 2001.\n Volunteer sample of 2832 persons aged 65 to 94 years recruited from senior housing, community centers, and hospital/clinics in 6 metropolitan areas in the United States.\n Participants were randomly assigned to 1 of 4 groups: 10-session group training for memory (verbal episodic memory; n = 711), or reasoning (ability to solve problems that follow a serial pattern; n = 705), or speed of processing (visual search and identification; n = 712); or a no-contact control group (n = 704). For the 3 treatment groups, 4-session booster training was offered to a 60% random sample 11 months later.\n Cognitive function and cognitively demanding everyday functioning.\n Thirty participants were incorrectly randomized and were excluded from the analysis. Each intervention improved the targeted cognitive ability compared with baseline, durable to 2 years (P<.001 for all). Eighty-seven percent of speed-, 74% of reasoning-, and 26% of memory-trained participants demonstrated reliable cognitive improvement immediately after the intervention period. Booster training enhanced training gains in speed (P<.001) and reasoning (P<.001) interventions (speed booster, 92%; no booster, 68%; reasoning booster, 72%; no booster, 49%), which were maintained at 2-year follow-up (P<.001 for both). No training effects on everyday functioning were detected at 2 years.\n Results support the effectiveness and durability of the cognitive training interventions in improving targeted cognitive abilities. Training effects were of a magnitude equivalent to the amount of decline expected in elderly persons without dementia over 7- to 14-year intervals. Because of minimal functional decline across all groups, longer follow-up is likely required to observe training effects on everyday function.", "To study the efficacy of cognitive rehabilitation combined with acetylcholinesterase inhibitor (AChE-I) treatment in patients with mild Alzheimer's disease and their relatives.\n Thirteen patients with mild Alzheimer's disease treated with rivastigmine 6-12 mg/day for more than two months started cognitive rehabilitation training. Before and after the cognitive rehabilitation training patients were assessed through cognitive tests, activities of daily living scale, neuropsychological battery and scales to evaluate caregivers' depressive and anxiety symptoms. Six patients were randomized to a combined treatment group (AChE-I plus cognitive rehabilitation and caregiver support) and seven patients to a control group (AChE-I only) and followed up for five months.\n Mini-Mental State Examination (MMSE) scores (p = 0.047) and backward digit span scores (p = 0.018) were significantly different between the groups on follow-up. The combined treatment group showed a better positive treatment effect on cognitive and neuropsychological tests applied to patients and reduction of psychiatric symptoms was observed in their caregivers (nonsignificant).\n Cognitive rehabilitation associated with AChE-I treatment can potentially be useful to stabilize or improve cognitive and functional performance of patients with mild Alzheimer's disease and can reduce caregivers' psychiatric symptoms." ]

[ "15154663", "11165126", "15015612", "16619567", "15774341", "12050495", "15898977", "11347286", "14581440" ]

[ "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 effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial.", "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.", "Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial.", "A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment.", "Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial.", "Immunotherapy with depigmented glutaraldehyde-polymerized extracts: changes in quality of life.", "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.", "Adjuvant chemotherapy for breast cancer: how presentation of recurrence risk influences decision-making." ]

[ "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.", "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.", "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.", "The objective of this randomised, multicentre, double-blind clinical trial was to investigate the impact of PS76A2, an aqueous mistletoe extract standardised to mistletoe lectins, on quality of life (QoL) in breast cancer patients. A total of 352 patients were randomly allocated to 2 groups receiving PS76A2 (15 ng mistletoe lectin/0.5 ml) or matching placebo twice weekly for 4 to 6 cycles of CMF (cyclophosphamide, methotrexate, fluorouracil) chemotherapy followed by 2 months follow-up. The primary efficacy end-point was the change from baseline of 3 FACT-G subscales (physical, emotional and functional well-being) during the fourth CMF cycle. Secondary measures included GLQ-8 (8 linear analogue self-assessment scales), Spitzer's uniscale and haematological variables. The main variables of safety analysis were adverse events, including injection site reactions and clinical laboratory tests. The results showed that physical, emotional and functional well-being improved upon PS76A2, but deteriorated following placebo. The treatment differences were statistically significant for the 3 subscales as well as for the summary score FACT-G, which was analysed as O'Brien's rank sum of its 3 subscales: The total score increased by 4.40 +/- 11.28, indicating a higher QoL after PS76A2, but decreased by 5.11 +/- 11.77 with placebo (p<0.0001). The GLQ-8 sum of 8 LASA scales was analysed as a summary score of GLQ-5 (sum of item nos. 1, 5, 6, 7, 8) and GLQ-3 (sum of item nos. 2, 3, 4). GLQ-5 characterises typical aspects of QoL, while GLQ-3 consists of 3 side-effects of CMF (feeling sick, numbness or pins and needles, loss of hair). GLQ-5 decreased by 42.9 +/- 125.0 upon PS76A2, indicating an improvement in QoL, but increased by 60.3 +/- 94.0 upon placebo (p<0.0001). GLQ-3 deteriorated in both groups (PS76A2: 13.9 +/- 52.4; placebo: 34.5 +/- 57.0), but the differences in favour of PS76A2 were, nevertheless, statistically significant (p=0.0007). The total score GLQ-8 improved by 28.9 +/- 154.6 after PS76A2 and deteriorated by 94.8 +/- 141.1 after placebo (p<0.0001). Spitzer's uniscale improved by 12.2 +/- 30.7 upon PS76A2 and deteriorated by 10.8 +/- 26.1 with placebo (p<0.0001). After follow-up without chemotherapy, a significant treatment difference in favour of PS76A2 was determined by means of FACT-G, GLQ-8 and Spitzer's uniscale. PS76A2 was well tolerated in this trial, with the exception of slight local reactions in 17.6% of the PS76A2 group. In conclusion, PS76A2 (15 ng mistletoe lectin/0.5 ml twice weekly) was shown to be safe and effective in improving QoL in breast cancer patients during chemotherapy and follow-up.", "This pilot study examined whether exercise as an adjunctive rehabilitation therapy could benefit women who have early stage breast cancer and are currently receiving chemotherapy/radiotherapy. The study was designed as a randomised controlled trial (RCT). Physical functioning, fatigue and Quality of Life (QoL) outcomes were evaluated pre and post a 12-week intervention. The results showed that after 12 weeks the women who participated in the exercise programme (n = 12) displayed significantly higher levels of physical functioning and reported higher QoL scores than the controls (n = 10). Changes in fatigue and satisfaction with life favoured the intervention group but did not reach significance. These results are encouraging and suggest that a structured group exercise programme during adjuvant treatment is a safe, well tolerated and effective way of providing physical and psychological health benefits to women during treatment for early stage breast cancer. Since this was a pilot study the numbers did not allow appropriately powered analyses of some variables of interest and favoured relatively young and socio-economically advantaged women. Future studies need to address these issues and determine if these short-term benefits can be sustained.", "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.", "Immunotherapy (IT) with modified allergens reduces allergic rhinitis (AR) symptoms and medications requirements. Improvement of quality of life (QOL) is a key point in the treatment of AR. The aim of this study was to provide evidence of changes related to the patient's QOL (well-being) induced by a modified (depigmented glutaraldehyde-polymerized) therapeutic vaccine and of its safety.\n Fifty-three patients with a well-documented clinical history of seasonal AR sensitized to Dactylis glomerata and Olea europaea pollens were included in a randomized clinical trial. Twenty-five patients (Group-A) received a mixture of D. glomerata and O. europaea pollen extracts and 28 patients received placebo (group-C). Any adverse event was recorded and graded in accordance with EAACI guidelines. RQLQ was recorded before the treatment (pollen season 2000) and after 1 year of treatment (pollen season 2001). Dose-response skin prick test with each allergen extract was conducted at baseline and at the end of the study.\n Each patient received 17 injections during this period. All patients completed the trial and no systemic adverse reactions were recorded. Symptom scores (P<0.001) and medication requirements (P<0.001) were significantly reduced in the IT group during the pollen season. This patient group also experienced greater and statistically significant improvement in overall RQLQ score and in five of the seven domains, all of them surpassing the threshold of 'minimal important difference' of 0.5 points.\n Results of this study provided evidence that IT with depigmented, glutaraldehyde-modified allergen extracts was well-tolerated and added beneficial effects to AR treatment in pollen allergic patients eliciting an improvement in QOL enough to justify a change in the patient's treatment.", "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.", "The purpose of this study was to examine the impact of four methods of communicating survival benefits on chemotherapy decisions. We hypothesized that the four methods of communicating mathematically equivalent risk information would lead to different chemotherapy decisions.\n Each participant received two hypothetical scenarios regarding their mother (a postmenopausal woman with an invasive, lymph node-negative, hormone receptor-positive breast cancer) and was asked to decide whether they would encourage their mother to take chemotherapy in addition to surgery and tamoxifen. In the part 1, participants received one of four methods of describing the chemotherapy survival benefit: (1) relative risk reduction, (2) absolute risk reduction, (3) absolute survival benefit, or (4) number needed to treat. In part 2, each participant received all four methods. Following each decision, participants were asked to rate their confidence and confusion regarding their decision.\n Participants included 203 preclinical medical students. In part 1, participants who received relative risk reduction information were significantly more likely to endorse chemotherapy. In part 2, there were no treatment decision differences when participants received all four methods of communicating survival benefits of chemotherapy. However, receiving all four methods led to significantly higher ratings of confusion. In deciding on endorsing chemotherapy, participants understood the information best when presented with data in the absolute survival benefit format.\n These results support the hypothesis that the method used to present information about chemotherapy influences treatment decisions. Absolute survival benefit is the most easily understood method of conveying the information regarding benefit of treatment." ]

[ "11517199", "11335736", "11433048", "15321956", "9797626", "14726421", "8120721", "7567201", "2505689" ]

[ "A randomised control study comparing the Infant Flow Driver with nasal continuous positive airway pressure in preterm infants.", "Randomized trial of nasal synchronized intermittent mandatory ventilation compared with continuous positive airway pressure after extubation of very low birth weight infants.", "A prospective randomized, controlled trial comparing synchronized nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure as modes of extubation.", "Prophylactic nasal continuous positive airways pressure in newborns of 28-31 weeks gestation: multicentre randomised controlled clinical trial.", "Randomised, controlled trial of nasal continuous positive airway pressure in the extubation of infants weighing 600 to 1250 g.", "A prospective, controlled trial of a protocol-based strategy to discontinue mechanical ventilation.", "Randomized, controlled trial of nasopharyngeal continuous positive airway pressure in the extubation of very low birth weight infants.", "Does continuous positive airway pressure (CPAP) during weaning from intermittent mandatory ventilation in very low birth weight infants have risks or benefits? A controlled trial.", "Randomised controlled trial of two methods of weaning from high frequency positive pressure ventilation." ]

[ "To compare the effectiveness of the Infant Flow Driver (IFD) with single prong nasal continuous positive airway pressure (nCPAP) in preterm neonates affected by respiratory distress syndrome.\n Randomised controlled study.\n Between September 1997 and March 1999, 36 preterm infants who were eligible for CPAP treatment were randomly selected for either nCPAP or IFD and studied prospectively for changes in oxygen requirement and/or respiratory rate. The requirement for mechanical ventilation, complications of treatment, and effects on mid-term outcome were also evaluated.\n Use of the IFD had a significantly beneficial effect on both oxygen requirement and respiratory rate (p < 0.0001) when compared with nCPAP. Moreover, O(2) requirement and respiratory rate were significantly decreased by four hours (p < 0.001 and p < 0.03 respectively). The probability of remaining supplementary oxygen free over the first 48 hours of treatment was significantly higher in patients treated with the IFD than with nCPAP (p < 0.02). IFD treated patients had a higher success (weaning) rate (94% v 72 %) and shorter duration of treatment (49.3 (31) v 56 (29.7) hours respectively; mean (SD)), although the difference was not significant.\n IFD appears to be a feasible device for managing respiratory distress syndrome in preterm infants, and benefits may be had with regard to oxygen requirement and respiratory rate when compared with nCPAP. The trend towards reduced requirement for mechanical ventilation, shorter clinical recovery time, and shorter duration of treatment requires further evaluation in a multicentre randomised clinical trial.", "To determine whether noninvasive, nasal synchronized intermittent mandatory ventilation (nSIMV) improves the likelihood that very low birth weight infants will be successfully extubated.\n Infants of <1251-g birth weight who were due to be extubated before 6 weeks of age were eligible once they were receiving <35% oxygen and were on a ventilator rate of <18 breaths per minute (bpm). Extubation was performed following intravenous loading with aminophylline, after a successful trial of 12 hours of endotracheal synchronized intermittent mandatory ventilation at a rate of 8. Infants were randomized to either nasal continuous positive airway pressure (nCPAP) at 6 cm H(2)O or nSIMV after extubation. nSIMV was commenced at a rate of 12 bpm with pressure on the ventilator set to achieve a delivered pressure of at least 12 cm H(2)O and a peak end expiratory pressure of 6 cm H(2)O. Continuous recording for diagnosis of apnea was performed for 72 hours after extubation. Objective criteria for failure of extubation were as follows: a PaCO(2) >70; FIO(2) >0.7; or severe recurrent apnea (>2 apneas requiring intermittent positive-pressure ventilation in 24 hours or >6 apneas >20 seconds per day). The study ended after 72 hours postextubation or when infants satisfied failure criteria. A sample size of 54 was determined by power analysis.\n Mean birth weight (831 standard deviation [SD]: 193 g) and gestation (26.3 SD: 1.8 weeks) did not differ between groups. Mean age at extubation was 7.6 (SD: 9.7) days, range 1 to 40 days. The nSIMV group had a lower incidence of failed extubation 4/27 compared with the continuous positive airway pressure group, 12/27. This was attributable to both a decreased incidence of apnea and a decreased incidence of hypercarbia. There was no increase in the incidence of abdominal distension or feeding intolerance.\n nSIMV is effective in preventing extubation failure in very low birth weight infants in the first 72 hours after extubation. Noninvasive ventilation may have other roles in the care of the very low birth weight infant.", "To determine whether synchronized nasal intermittent positive pressure ventilation (SNIPPV) would decrease extubation failure compared with nasal continuous positive airway pressure (NCPAP) in preterm infants being ventilated for respiratory distress syndrome (RDS).\n Infants who were </=34 weeks' gestational age and who were ventilated for RDS were randomized to either SNIPPV or NCPAP after extubation. The criteria for extubation were peak inspiratory pressure of </=16 cm H(2)O, positive end expiratory pressure of </=5 cm H(2)O, intermittent mandatory ventilation rate of 15 to 25, and fraction of inspired oxygen </=0.35. Pulmonary function tests (PFT) were obtained before extubation. After extubation, blood gases were monitored for a minimum of 72 hours. Success was defined as remaining in the selected mode of treatment or demonstrating improvement (switching to oxyhood/nasal cannula/room air) by 72 hours.\n Thirty-two (94%) of 34 infants were extubated successfully with the use of SNIPPV versus 18 (60%) of 30 with the use of NCPAP (P <.01). There was no difference in apnea/bradycardia episodes in the 2 groups during the 72-hour study period. Among 55 infants who had PFT, 80% (8 of 10) with dynamic lung compliance of >/=0.5 mL/kg/cm H(2)O and expiratory airway resistance of </=70 cm H(2)O/L/s were extubated successfully. In infants with poor lung function (dynamic lung compliance: <0.5 mL/kg/cm H(2)O; expiratory airway resistance: >70 cm H(2)O/L/s), successful extubation was seen in 93% (27 of 29) in the SNIPPV group and 60% (15 of 25) in the NCPAP group. When weight was controlled for at the time of extubation, the odds of success in the SNIPPV group were 21.1 times higher (95% confidence interval: 3.4, 130.1) than that of the NCPAP group.\n SNIPPV is more effective than NCPAP in weaning infants with RDS from the ventilator. PFT may be useful in predicting successful extubation.", "The role of nasal continuous positive airways pressure (nCPAP) in the management of respiratory distress syndrome in preterm infants is not completely defined.\n To evaluate the benefits and risks of prophylactic nCPAP in infants of 28-31 weeks gestation.\n Multicentre randomised controlled clinical trial.\n Seventeen Italian neonatal intensive care units.\n A total of 230 newborns of 28-31 weeks gestation, not intubated in the delivery room and without major malformations, were randomly assigned to prophylactic or rescue nCPAP.\n Prophylactic nCPAP was started within 30 minutes of birth, irrespective of oxygen requirement and clinical status. Rescue nCPAP was started when Fio2 requirement was > 0.4, for more than 30 minutes, to maintain transcutaneous oxygen saturation between 93% and 96%. Exogenous surfactant was given when Fio2 requirement was > 0.4 in nCPAP in the presence of radiological signs of respiratory distress syndrome.\n Primary end point: need for exogenous surfactant. Secondary end points: need for mechanical ventilation and incidence of air leaks.\n Surfactant was needed by 22.6% in the prophylaxis group and 21.7% in the rescue group. Mechanical ventilation was required by 12.2% in both the prophylaxis and rescue group. The incidence of air leaks was 2.6% in both groups. More than 80% of both groups had received prenatal steroids.\n In newborns of 28-31 weeks gestation, there is no greater benefit in giving prophylactic nCPAP than in starting nCPAP when the oxygen requirement increases to a Fio2 > 0.4.", "To determine whether extubation to nasal continuous airway pressure (NCPAP) results in a greater proportion of infants remaining free of additional ventilatory support for one week after extubation compared with those extubated directly to headbox oxygen.\n A randomised, controlled, clinical trial was conducted at the neonatal intensive care unit of the Royal Women's Hospital, Melbourne, of infants with birthweights between 600 and 1250 g, ventilated via an endotracheal tube for more than 12 hours, requiring less than 50% oxygen, a ventilator rate < or = 20/minute, considered by the clinical management team to be ready for extubation. Infants were randomly allocated either to NCPAP or to oxygen administered via a headbox. Success was defined by no requirement for additional ventilatory support over the week following extubation. Failure criteria were (i) apnoea; (ii) absolute increase in oxygen requirement greater than 15% above than required before extubation; or (iii) respiratory acidosis (pH < 7.25 with pCO2 > 6.67 kPa).\n Thirty one of 47 (66%) infants were successfully extubated to NCPAP compared with 18 of 45 (40%) for headbox oxygen. The increase in failure rate in the headbox group was due primarily to increased oxygen requirements in this group. Of the 27 who failed headbox oxygen, 26 were given a trial of NCPAP and 13 did not require endotracheal reintubation. There was no significant difference between the groups in the total number of days of assisted ventilation or the duration of inpatient stay.\n NCPAP applied prophylactically after endotracheal extubation reduces the incidence of adverse clinical events that lead to failure of extubation in the seven days after extubation. This reduction is clinically important. The benefits of NCPAP do not seem to be associated with an increased incidence of unwanted side effects.", "Weaning protocols can improve outcomes, but their efficacy may vary with patient and staff characteristics. In this prospective, controlled trial, we compared protocol-based weaning to usual, physician-directed weaning in a closed medical intensive care unit (ICU) with high physician staffing levels and structured, system-based rounds. Adult patients requiring mechanical ventilation for more than 24 hours were assigned to usual care (UC) or protocol weaning based on their hospital identification number. Patients assigned to UC (n=145) were managed at their physicians' discretion. Patients assigned to protocol (n=154) underwent daily screening and a spontaneous breathing trial by respiratory and nursing staff without physician intervention. There were no significant baseline differences in patient characteristics between groups. The proportion of patients (protocol vs. UC) who successfully discontinued mechanical ventilation (74.7% vs. 75.2%, p=0.92), duration of mechanical ventilation (median [interquartile range]: 60.4 hours [28.6-167.0 hours] vs. 68.0 hours [27.1-169.3 hours], p=0.61), ICU (25.3% vs. 28.3%) and hospital mortality (36.4% vs. 33.1%), ICU length of stay (115 vs. 146 hours), and rates of reinstituting mechanical ventilation (10.3% vs. 9.0%) was similar. We conclude that protocol-directed weaning may be unnecessary in a closed ICU with generous physician staffing and structured rounds.", "We conducted a prospective, randomized controlled trial to determine whether extubation of very low birth weight infants was facilitated by the use of nasopharyngeal continuous positive airway pressure (CPAP). Eligible infants included patients weighing 600 to 1500 gm at birth who required tracheal intubation within 48 hours of birth and who met specific predetermined criteria for extubation by day 14 of life. We also sought to determine whether varying the duration of nasopharyngeal CPAP influenced the likelihood of successful extubation. Infants underwent random assignment to receive nasopharyngeal CPAP until resolution of lung disease (n = 40), 6 hours of nasopharyngeal CPAP (n = 42), or oxygen supplementation delivered by hood (n = 42). Extubation failure was predefined as a requirement for > or = 80% oxygen, pH < or = 7.20, severe apnea, or predefined clinical deterioration, and extubation success was predefined as the ability to remain free of a requirement for mechanical ventilation for 7 days and a 66% reduction in the need for supplemental oxygen. Each group was similar with regard to race, sex, and birth weight. Extubation was successful in 62%, 61%, and 60% of infants. After stratification by birth weight, there were no significant differences in the rates of successful extubation among the treatment groups. We conclude that nasopharyngeal CPAP does not improve the likelihood of successful extubation of very low birth weight infants who are ready for extubation within the first 2 weeks of life.", "The purpose of this study was to evaluate three ventilator weaning strategies and to evaluate whether the use of continuous positive airway pressure (CPAP) via a nasopharyngeal or endotracheal tube would increase the likelihood of extubation failure in very low birth weight (VLBW) infants.\n We studied prospectively 87 preterm infants (mean +/- SD; birth weight: 1078 +/- 188 g; gestational age: 28.8 +/- 2.2 weeks) who were in the process of being weaned from intermittent mandatory ventilation (IMV). Infants were assigned by systematic sampling to one of the following three treatment groups: (1) direct extubation from IMV (D.EXT) (n = 30); (2) preextubation endotracheal CPAP (ET-CPAP) for 12-24 hr (n = 28); or (3) postextubation nasopharyngeal CPAP (NP-CPAP) for 12-24 hr (n = 29). Failure was defined as the need for resumption of mechanical ventilation within 72 hr of extubation due to frequent or severe apnea and/or respiratory failure (pH < 7.25, PaCO2 > 60 mm Hg, and/or requirement for oxygen FiO2 > 60%).\n There were no significant differences in failure rates among the three procedures. Failures were 2/30 (7%) in D.EXT; 4/28 (14%) in ET-CPAP; and 7/29 (24%) in the NP-CPAP. There were also no differences in FiO2, PaO2, and respiratory rates before and after discontinuation of IMV among the three groups. PaCO2 values were slightly higher in the NP-CPAP group 12-24 hr after weaning from IMV.\n We were unable to demonstrate a clear difference in extubation outcome by use of CPAP administered via an endotracheal or nasopharyngeal tube when compared to direct extubation from low-rate IMV in VLBW infants.", "Forty preterm infants suffering from respiratory distress syndrome were entered into a randomised controlled trial to assess the importance of the length of inspiratory time during weaning from high frequency positive pressure ventilation (HFPPV). Two weaning regimes were compared: in one (group A) inspiratory time was limited to 0.5 seconds throughout weaning, in the other (group B) ventilator rate was reduced by increasing both inspiratory and expiratory time (inspiration:expiration ratio constant) until inspiratory time reached 1.0 seconds. At ventilator rates of 20 and 40 breaths/minute an acute comparison was made in all 40 infants of the two inspiratory times; despite the lower mean airway pressure associated with the shorter inspiratory time blood gases were maintained. There was no difference in the incidence of pneumothoraces or need for reventilation between the two regimens but infants in group A had a shorter duration of weaning. We conclude limitation of inspiratory time to 0.5 seconds during weaning from HFPPV is advantageous to preterm infants with respiratory distress syndrome." ]

[ "12463661", "16452734", "11284567", "17322427", "2693355", "17142407", "8117509", "11154750", "7263746" ]

[ "Hemiarthroplasty versus internal fixation for displaced intracapsular hip fractures in the elderly. A randomised trial of 455 patients.", "Randomized comparison of reduction and fixation, bipolar hemiarthroplasty, and total hip arthroplasty. Treatment of displaced intracapsular hip fractures in healthy older patients.", "Treatment for displaced intracapsular fracture of the proximal femur. A prospective, randomised trial in patients aged 65 to 79 years.", "A randomised controlled trial comparing bipolar hemiarthroplasty with total hip replacement for displaced intracapsular fractures of the femoral neck in elderly patients.", "Displaced subcapital fractures of the femur: a prospective randomized comparison of internal fixation, hemiarthroplasty and total hip replacement.", "Total hip arthroplasty and hemiarthroplasty in mobile, independent patients with a displaced intracapsular fracture of the femoral neck. A randomized, controlled trial.", "Osteosynthesis versus endoprosthesis in the treatment of unstable intracapsular hip fractures in the elderly. A randomised clinical trial.", "Internal fixation versus hemiarthroplasty versus total hip arthroplasty for displaced subcapital fractures of femur--13 year results of a prospective randomised study.", "Internal fixation versus hemiarthroplasty for the displaced subcapital fracture of the femur. A prospective randomised study." ]

[ "A total of 455 patients aged over 70 years with a displaced intracapsular fracture of the proximal femur was randomised to be treated either by hemiarthroplasty or internal fixation. The preoperative characteristics of the patients in both groups were similar. Internal fixation has a shorter length of anaesthesia (36 minutes versus 57 minutes, p < 0.0001), lower operative blood loss (28 ml versus 177 ml, p < 0.0001) and lower transfusion requirements (0.04 units versus 0.39 units, p < 0.0001). In the internal fixation group 90 patients required 111 additional surgical procedures while only 15 additional operations on the hip were needed in 12 patients in the arthroplasty group. There was no statistically significant difference in mortality between the groups at one year (61/226 versus 63/229, p = 0.91), but there was a tendency for an improved survival in the older less mobile patients treated by internal fixation. For the survivors assessed at one, two and three years from injury there were no differences with regard to the outcome for pain and mobility. Limb shortening was more common after internal fixation (7.0 mm versus 3.6 mm, p = 0.004). We recommend that displaced intracapsular fractures in the elderly should generally be treated by arthroplasty but that internal fixation may be appropriate for those who are very frail.", "Orthopaedic surgeons vary in their management of displaced intracapsular fractures of the hip in healthy older patients. The aim of this investigation was to determine the functional, clinical, and resource consequences of three different types of surgical treatment.\n The study was a multicenter randomized controlled trial. Reduction and fixation was compared with bipolar hemiarthroplasty with cement and total hip replacement with cement. Participating surgeons elected to randomize their patients to be treated with either one of the three types of procedures or with either fixation or bipolar hemiarthroplasty. Functional outcomes were measured with a hip-rating questionnaire and the EuroQol health status measure. Clinical outcomes included mortality and complications. The direct health service costs were compared. Participants were followed up for two years.\n Two hundred and seven patients were randomized to be treated with one of the three operations, and ninety-one were randomized to be treated with either fixation or bipolar hemiarthroplasty. There were no differences in the mortality rates among the treatment groups. The rate of secondary surgery was highest in the fixation group (39% compared with 5% in the group treated with bipolar hemiarthroplasty and 9% in the group treated with total hip replacement). The fixation group had the worst hip-rating-questionnaire and EuroQol scores at four and twelve months. The total hip replacement group had significantly better functional outcome scores at twenty-four months than the other two groups. Although fixation was initially the least costly procedure, this short-term advantage was eroded by significantly higher costs for subsequent hip-related hospital admissions.\n Arthroplasty is more clinically effective and cost-effective than reduction and fixation in healthy older patients with a displaced intracapsular fracture of the hip. The long-term results of total hip replacement may be better than those of bipolar hemiarthroplasty.", "We performed a prospective, randomised trial comparing three treatments for displaced intracapsular fractures of the hip in 280 patients aged 65 to 79 years. The mean patient survival was significantly higher in the group undergoing reduction and internal fixation (79 months) compared with that with a cemented Thompson hemiarthroplasty or a cemented Monk bipolar hemiarthroplasty (61 months and 68 months, respectively). After three years, 32 of 93 patients (34.4%) who had undergone fixation had local complications, necessitating further intervention in 28 (30%). There were no significant differences in the functional outcome in survivors, who were reviewed annually to five years. Either reduction and internal fixation or cemented hemiarthroplasty may be offered as alternative treatments for a displaced intracapsular fracture in a mobile and mentally competent patient under the age of 80 years. The choice of procedure by the patient and the surgeon should be determined by the realisation that the use of internal fixation is associated with a 30% risk of failure requiring further surgery. If this is accepted, however, hemiarthroplasty is avoided, which, in our study has a significantly shorter mean survival time. The use of a bipolar prosthesis has no significant advantage.", "The best treatment for the active and lucid elderly patient with a displaced intracapsular fracture of the femoral neck is still controversial. Randomised controlled trials have shown that a primary total hip replacement is superior to internal fixation as regards the need for secondary surgery, hip function and health-related quality of life. Despite good results achieved with total hip replacement in this group, most orthopaedic surgeons still advocate hemiarthroplasty for this injury. We studied 120 patients with a mean age of 81 years (70 to 90) with an acute displaced intracapsular fracture of the femoral neck. They were randomly allocated to be treated with either a bipolar hemiarthroplasty or total hip replacement. Outcome measurements included peri-operative data, general and hip-specific complications, hip function and health-related quality of life. The patients were reviewed at four and 12 months. The duration of surgery was longer in the total hip replacement group (102 minutes (70 to 151)) versus 78 minutes (43 to 131) (p<0.001), and the intra-operative blood loss was increased 460 ml (100 to 1100) versus 320 ml (50 to 850) (p<0.001), but there were no differences between the groups regarding any complications or mortality. There were no dislocations in either group. Hip function measured by the Harris hip score was significantly better in the total hip replacement group at both follow-up periods (p=0.011 and p<0.001, respectively). The health-related quality of life measure was in favour of the total hip replacement group but did not reach statistical significance (p=0.818 at four months and p=0.636 at 12 months). These results indicate that a total hip replacement provides better function than a bipolar hemiarthroplasty as soon as one year post-operatively, without increasing the complication rate. We recommend total hip replacement as the primary treatment for this group of patients.", "In a prospective trial of 278 patients aged over 65 years, treatment of displaced subcapital fractures was randomly allocated to closed reduction and internal fixation with a sliding compression screwplate, Moore hemiarthroplasty, or total hip treatment with a Howse semicaptive prosthesis. One year after operation there was little difference between the three groups in mortality (25 per cent) or general complications. The revision rate within the first year was highest for internal fixation (25 per cent), but many of the replacements also required a further anaesthetic for reduction of a dislocation (Moore, 11 per cent; Howse 12.5 per cent). Total hip replacement resulted in the least pain and most mobility at 1 year, while hemiarthroplasty was worst in these respects. We conclude that internal fixation and particularly primary total hip replacement should be given serious consideration in the management of the elderly patient with a displaced subcapital fracture.", "Hemiarthroplasty and total hip arthroplasty are commonly used to treat displaced intracapsular fractures of the femoral neck, but each has disadvantages and the optimal treatment of these fractures remains controversial.\n In the present prospectively randomized study, eighty-one patients who had been mobile and lived independently before they had sustained a displaced fracture of the femoral neck were randomized to receive either a total hip arthroplasty or a hemiarthroplasty. The mean age of the patients was seventy-five years. Outcome was assessed with use of the Oxford hip score, and final radiographs were assessed.\n After a mean duration of follow-up of three years, the mean walking distance was 1.17 mi (1.9 km) for the hemiarthroplasty group and 2.23 mi (3.6 km) for the total hip arthroplasty group, and the mean Oxford hip score was 22.3 for the hemiarthroplasty group and 18.8 for the total hip arthroplasty group. Patients in the total hip arthroplasty group walked farther (p=0.039) and had a lower (better) Oxford hip score (p=0.033) than those in the hemiarthroplasty group. Twenty of thirty-two living patients in the hemiarthroplasty group had radiographic evidence of acetabular erosion at the time of the final follow-up. None of the hips in the hemiarthroplasty group dislocated, whereas three hips in the total hip arthroplasty group dislocated. In the hemiarthroplasty group, two hips were revised to total hip arthroplasty and three additional hips had acetabular erosion severe enough to indicate revision. In the total hip arthroplasty group, one hip was revised because of subsidence of the femoral component.\n Total hip arthroplasty conferred superior short-term clinical results and fewer complications when compared with hemiarthroplasty in this prospectively randomized study of mobile, independent patients who had sustained a displaced fracture of the femoral neck.", "Forty-three elderly patients with an intracapsular hip fracture were selected for a prospective randomised trial comparing osteosynthesis (DHS) versus primary hemiarthroplasty (HA) with a 3-year follow-up. The duration of the operation and the perioperative blood loss were significantly shorter in DHS, but inadequate reduction and/or fixation led to serious problems in this group. Clinical morbidity was lower after DHS. No difference could be demonstrated in the mortality rates, fracture- or operation-related complications or the need for secondary intervention. Reintervention could be carried out without additional risk in both groups and did not lead to poor end results. Comparable results were obtained with both methods up to 24 months. At the 36-month follow-up, a significantly worse outcome could be demonstrated in the HA group. We conclude that osteosynthesis is justified as the primary treatment of displaced intracapsular hip fractures in elderly patients. Endoprosthetic replacement can be safely used in cases where osteosynthesis has failed.", "In this prospective randomised trial we compare the mortality, morbidity and functional results of patients following each of the three principal methods of treatment for displaced subcapital fractures of the femur. Two hundred and ninety patients over the age of 65 years were included and randomly allocated to undergo closed reduction and internal fixation with a sliding compression screw plate or uncemented Austin Moore hemiarthroplasty or cemented Howse II total hip arthroplasty (THA). Nineteen patients were subsequently excluded. The 13 year results show that there was no statistical difference in the mortality between the three groups (81, 85 and 91% respectively). Internal fixation and hemiarthroplasty groups fared poorly with a revision rate of 33 and 24%, respectively, compared with 6.75% in the THA group. The dislocation rate was 13% following hemiarthroplasty and 20% following THA. Average Harris hip scores were 62, 55 and 80, respectively, for the internal fixation, hemiarthroplasty and THA groups. In the long term, both internal fixation and hemiarthroplasty resulted in a poor outcome with respect to pain and mobility. Despite high early complications, THA resulted in least pain and most mobility both in the short and long-term and was encouraging with a revision rate of only 6.25%. THA should be seriously considered in physiologically active patients with a displaced subcapital fracture of the femur.", "A prospective randomised trial of surgical treatment for the displaced subcapital femoral fracture in patients of 70 years or more is presented. Two hundred and eighteen patients were randomly allocated into one of three treatment groups: manipulative reduction and internal fixation using Garden screws; Thompson hemiarthroplasty through a posterior (Moore) approach; and Thompson hemiarthroplasty through an anterolateral (McKee) approach. There is no significant difference in the mortality of the internal fixation and posterior arthroplasty groups. Both groups showed a significantly higher mortality than patients operated on through the anterior approach. The technical results of operation were worse in the internally fixed group, with only 40 per cent being satisfactory. Mobilisation was best achieved after the posterior approach. It is concluded that Thompson hemiarthroplasty, using an anterolateral approach, is the safest operation in this group of patients." ]

[ "15832550", "17172550", "16271570", "17709994", "17678656", "11732835", "15673841", "15835284", "18441040" ]

[ "Effects of constraint-induced movement therapy in young children with hemiplegic cerebral palsy: an adapted model.", "Constraint-induced movement therapy during early stroke rehabilitation.", "Efficacy of forced-use therapy in hemiplegic cerebral palsy.", "Repetitive transcranial magnetic stimulation as an adjunct to constraint-induced therapy: an exploratory randomized controlled trial.", "Kinematic and clinical analyses of upper-extremity movements after constraint-induced movement therapy in patients with stroke: a randomized controlled trial.", "Modified constraint induced therapy: a randomized feasibility and efficacy study.", "Modified constraint-induced therapy in acute stroke: a randomized controlled pilot study.", "Effectiveness of modified constraint-induced movement therapy on upper limb function in stroke subjects.", "Short- and long-term outcome of constraint-induced movement therapy after stroke: a randomized controlled feasibility trial." ]

[ "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.", "Limited data are available about the effectiveness of early rehabilitation after stroke.\n This is the 1st randomized controlled trial of constraint-induced movement therapy (CIMT) in subacute stroke to investigate neurophysiologic mechanisms and long-term outcome.\n Within 2 weeks after stroke, 23 patients with upper extremity (UE) weakness were randomized to 2 weeks of CIMT or traditional therapy at an equal frequency of up to 3 h/day. Motor function of the affected UE was blindly assessed before treatment, after treatment, and 3 months after stroke. Transcranial magnetic stimulation (TMS) measured the cortical area evoking movement of the affected hand.\n Long-term improvement in motor function of the affected UE did not differ significantly between patients who received CIMT versus intensive traditional therapy. All outcome comparisons showed trends favoring CIMT over intensive traditional therapy, but none was statistically significant except for improvements in the Fugl-Meyer (FM) UE motor scale immediately following treatment and in reported quality of hand function at 3 months. Improvement in UE motor function on the FM was associated with a greater number of sites on the affected cerebral hemisphere where responses of the affected hand were evoked by TMS.\n Future trials of CIMT during early stroke rehabilitation need greater statistical power, more inclusive eligibility criteria, and improved experimental control over treatment intensity. The relationship between changes in motor function and in evoked motor responses suggests that motor recovery during the 1st 3 months after stroke is associated with increased motor excitability of the affected cerebral hemisphere.", "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.", "To test the potential adjuvant effect of repetitive transcranial magnetic stimulation (rTMS) on motor learning in a group of stroke survivors undergoing constraint-induced therapy (CIT) for upper-limb hemiparesis.\n This was a prospective randomized, double-blind, sham-controlled, parallel group study. Nineteen individuals, one or more years poststroke, were randomized to either a rTMS + CIT (n = 9) or a sham rTMS + CIT (n = 10) group and participated in the 2-wk intervention.\n Regardless of group assignment, participants demonstrated significant gains on the primary outcome measures: the Wolf Motor Function Test (WMFT) and the Motor Activity Log (MAL)--Amount of Use, and on secondary outcome measures including the Box and Block Test (BBT) and the MAL--How Well. Participants receiving rTMS failed to show differential improvement on either primary outcome measure.\n Although this study provided further evidence that even relatively brief sessions of CIT can have a substantial effect, it provided no support for adjuvant use of rTMS.", "To study the effects of constraint-induced movement therapy (CIMT) relative to traditional intervention on motor-control strategies for upper-arm reaching and motor performance at the impairment and functional levels in stroke patients.\n Two-group randomized controlled trial (RCT); pretreatment and posttreatment measures.\n Rehabilitation clinics.\n Forty-seven stroke patients (mean age, 55y) 3 weeks to 37 months postonset of a first-ever cerebrovascular accident.\n Forty-seven patients received either CIMT (restraint of the less affected hand combined with intensive training of the more affected upper extremity) or traditional intervention (control treatment) during the study. The treatment intensity was matched between the 2 groups (2h/d, 5d/wk for 3wk).\n Outcomes were evaluated using (1) kinematic variables of reaching movement used to describe the control strategies for reaching, (2) the Fugl-Meyer Assessment (FMA) of motor-impairment severity, and (3) the Motor Activity Log (MAL) evaluating the functional ability of the upper extremity.\n After treatment, the CIMT group showed better strategies of reaching control than the control group (P<.03). The CIMT group also showed less motor impairment on the FMA (P=.019) and higher functional ability on the MAL (P<.001).\n This study is the first RCT to show differences in motor-control strategies as measured by kinematic variables after CIMT versus traditional intervention. In addition to improving motor performance at the impairment and functional levels, CIMT conferred therapeutic benefits on control strategies determined by kinematic analysis.", "This case series examined the feasibility and efficacy of a modified constraint induced therapy (CIT) protocol administered on an outpatient basis. The Fugl-Meyer Assessment of Motor Recovery After Stroke (Fugl), Action Research Arm Test (ARA), Wolf Motor Function Test (WMFT), and Motor Activity Log (MAL) were administered to six patients between 2 and 6 months poststroke (CVA) exhibiting stable motor deficits and learned nonuse of the affected limb. Two patients then participated in half-hour physical and occupational therapy sessions three times/week for 10 weeks. During the same period, their unaffected arms and hands were restrained 5 days/week during 5 hours identified as times of frequent use. Two other patients received regular therapy and two control patients received no therapy. The ARA, Fugl, WMFT, and MAL were again administered after 10 weeks. Patients receiving modified CIT exhibited substantial improvements on the Fugl, ARA, and WMFT, as well as increases in amount and quality of use of the limb using the MAL. Patients receiving traditional or no therapy exhibited no improvements. Results suggest that modified CIT may be an efficacious method of improving function and use of the affected arms of patients exhibiting learned nonuse.", "To determine modified constraint-induced therapy (mCIT) feasibility and compare its efficacy to traditional rehabilitation (TR) in acute stroke patients exhibiting upper limb hemiparesis.\n Before-after, multiple baseline, randomized controlled pilot study.\n Rehabilitation hospital.\n Ten stroke patients < 14 d poststroke and exhibiting upper limb hemiparesis and affected limb nonuse.\n Five patients were administered mCIT, consisting of structured therapy emphasizing more affected arm use in valued activities 3 d/week for 10 weeks and less affected arm restraint 5 d/week for 5 h. Five other patients received 1/2 sessions of traditional motor rehabilitation for the affected arm, which included affected limb manual dexterity exercises and stretching, as well as compensatory strategies with the unaffected limb. The TR regimens occurred 3 d/week for 10 weeks.\n The Fugl-Meyer Assessment of Motor Recovery (Fugl-Meyer), Action Research Arm Test (ARA), and Motor Activity Log (MAL).\n Before intervention, all patients exhibited stable motor deficits and more affected arm nonuse. After intervention, mCIT patients displayed increased affected arm use (+ 2.43 on the MAL amount of use scale), uniformly exhibited increases on the Fugl-Meyer and ARA (mean change scores = + 18.7 and + 21.7, respectively), and were able to again perform valued activities. TR patients exhibited nominal change in affected limb use (+ 0.07 on the MAL amount of use scale) and modest changes on the Fugl-Meyer and ARA (+ 4.4 and + 4.8, respectively). Fugl-Meyer and ARA changes were significant for the mCIT group only (P < 0.01).\n mCIT is a promising regimen for improving more affected limb use and function in acute cerebrovascular accident. However, larger confirmatory studies need to be performed.", "Of all stroke survivors, more than 50% are left with motor disabilities. Impairment of upper limb movement is a common motor disability. Constraint-Induced Movement Therapy (CIMT) is an intervention which has been used for the treatment of upper extremity motor disabilities in stroke patients. Although CIMT is an effective intervention, a recent survey revealed that this procedure is viewed with apprehension by many clinicians because of concerns about practicality and resource issues. We developed a modified CIMT that reserves the massed training of the affected arm without any physical restriction of the intact one and then used it on our stroke patients. This study was designed to evaluate the effectiveness of this Modified-Constraint-Induced Movement Therapy (m-CIMT).\n Thirty stroke patients were randomly assigned to either an m-CIMT (n=13) or a control group (n=17). Subjects in the m-CIMT group received a 2-week course of m-CIMT. Outcomes were evaluated using the Wolf Motor Function Test (WMFT).\n After only 2 weeks of training, significant differences (p<0.05) in favor of m-CIMT were found in the following 6 elements of the WMFT: Extend elbow with weight, Lift pencil, Stack checkers, Flip cards, Turn key in lock, and Lift basket.\n The present study shows that our m-CIMT is useful in improving the function of the affected upper extremity in stroke patients.", "Constraint-induced movement therapy (CIMT) is a method to improve motor function in the upper extremity following stroke. The aim of this trial was to determine the effect and feasibility of CIMT compared with traditional rehabilitation in short and long term.\n A randomized controlled trial.\n An inpatient rehabilitation clinic.\n Thirty patients with unilateral hand impairment after stroke.\n Six hours arm therapy for 10 consecutive weekdays, while using a restraining mitten on the unaffected hand.\n The patients were assessed at baseline, post-treatment and at six-month follow-up using the Wolf Motor Function Test as primary outcome measure and the Motor Activity Log, Functional Independence Measure and Stroke Impact Scale as secondary measurements.\n The CIMT group (n=18) showed a statistically significant shorter performance time (4.76 seconds versus 7.61 seconds, P= 0.030) and greater functional ability (3.85 versus 3.47, P= 0.037) than the control group (n=12) on the Wolf Motor Function Test at post-treatment assessment. There was a non-significant trend toward greater amount of use (2.47 versus 1.97, P= 0.097) and better quality of movement (2.45 versus 2.12, P=0.105) in the CIMT group according to the Motor Activity Log. No such differences were seen on Functional Independence Measure at the same time. At six-month follow-up the CIMT group maintained their improvement, but as the control group improved even more, there were no significant differences between the groups on any measurements.\n CIMT seems to be an effective and feasible method to improve motor function in the short term, but no long-term effect was found." ]

[ "2792781", "15774341", "14710804", "17601464", "20347838", "12568272", "8104964", "3094804", "2218150" ]

[ "Effect of exercise on postural sway in the elderly.", "A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment.", "Feasibility of exercise during treatment for multiple myeloma.", "High-frequency whole-body vibration improves balancing ability in elderly women.", "The effect of acupressure on quality of sleep in Iranian elderly nursing home residents.", "Effectiveness of auricular therapy on sleep promotion in the elderly.", "Hypnotics as concurrent medication in depression. A placebo-controlled, double-blind comparison of flunitrazepam and lormetazepam in patients with major depression, treated with a (tri)cyclic antidepressant.", "Improvement in bronchial hyper-responsiveness in patients with moderate asthma after treatment with a hypnotic technique: a randomised controlled trial.", "Intervention against long-term use of hypnotics/sedatives in general practice." ]

[ "Fifty female subjects, aged 72-92 (mean 82) years, were enrolled in a 12-week (36 classes) exercise program aimed at increasing postural stability. Subjects were residents of sheltered apartments, rest homes or nursing homes, well enough and mobile enough to participate in the classes. The subjects were randomized into an exercise or a control group. Their postural sway, standing at rest on a force platform, was measured with eyes open and eyes closed. The groups were well matched in all respects. The results showed no improvement in the postural sway as a result of the exercise program. We hypothesize that increasing postural sway in the elderly represents a deterioration in, for the most part, the nervous system and may at this extreme of life indicate an irreversible loss of function. For this reason no improvement in postural sway may be possible.", "This pilot study examined whether exercise as an adjunctive rehabilitation therapy could benefit women who have early stage breast cancer and are currently receiving chemotherapy/radiotherapy. The study was designed as a randomised controlled trial (RCT). Physical functioning, fatigue and Quality of Life (QoL) outcomes were evaluated pre and post a 12-week intervention. The results showed that after 12 weeks the women who participated in the exercise programme (n = 12) displayed significantly higher levels of physical functioning and reported higher QoL scores than the controls (n = 10). Changes in fatigue and satisfaction with life favoured the intervention group but did not reach significance. These results are encouraging and suggest that a structured group exercise programme during adjuvant treatment is a safe, well tolerated and effective way of providing physical and psychological health benefits to women during treatment for early stage breast cancer. Since this was a pilot study the numbers did not allow appropriately powered analyses of some variables of interest and favoured relatively young and socio-economically advantaged women. Future studies need to address these issues and determine if these short-term benefits can be sustained.", "Fatigue and insomnia are problems for patients with cancer. Research findings show that aerobic exercise decreases cancer-related fatigue. Because patients with cancer who have skeletal muscle wasting may not obtain maximum benefit from aerobic exercise training, exercise programs may need to include resistance training. Thus far, testing exercise as an intervention for fatigue has focused on patients with breast cancer and excluded patients with bone metastasis. There is a need to test the feasibility and effectiveness of exercise for patients with other types of cancer and with bone involvement. The effect of aerobic and strength resistance training on the sleep of patients with cancer has not been tested. A pilot/feasibility study with a randomized controlled design was conducted to investigate home-based exercise therapy for 24 patients receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation as treatment for multiple myeloma. None of the patients injured themselves. Because of the small sample size in the feasibility study, the effect of exercise on lean body weight was the only end point that obtained statistical significance. However, the results suggest that an individualized exercise program for patients receiving aggressive treatment for multiple myeloma is feasible and may be effective for decreasing fatigue and mood disturbance, and for improving sleep.", "To investigate the efficacy of high-frequency whole-body vibration (WBV) on balancing ability in elderly women.\n Randomized controlled trial. Subjects were randomized to either the WBV intervention or the no-treatment control group.\n Community-living elderly women.\n Sixty-nine elderly women aged 60 or above without habitual exercise.\n Side alternating WBV at 20Hz with 3 minutes a day and 3 days a week for 3 months in the WBV intervention group. Those in control group remained sedentary with normal daily life for the whole study period.\n Limits of stability in terms of reaction time, movement velocity, directional control, endpoint excursion, maximum excursion, and the functional reach test were performed at baseline and endpoint.\n Significant enhancement of stability was detected in movement velocity (P<.01), maximum point excursion (P<.01), in directional control (P<.05).\n WBV was effective in improving the balancing ability in elderly women. This also provides evidence to support our user-friendly WBV treatment protocol of 3 minutes a day for the elderly to maintain their balancing ability and reduce risks of fall.", "Sleep disturbances are very common in elderly people and Traditional Chinese acupressure a noninvasive technique that promotes health and comfort recently has been used in this regard. The purpose of the present study was to evaluate the potential beneficial effects of acupressure on a group of institutionalized elders experiencing sleep disturbances.\n A randomized controlled clinical trial was conducted to test the effectiveness of acupressure on quality of sleep of elderly residing in a Nursing home. The Pittsburgh Sleep Quality index (PSQI) questionnaire was used as a screening tool to select 90 residents with moderate to marked sleep disturbances. The elders were randomly assigned to an acupressure group, a sham acupressure group and a control group by Balanced randomization method.\n There were significant differences between the acupressure group and the control group in subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency and sleep disturbance. But no significant differences were found in sleep indices between the sham acupressure group and the control group. Sleep log data showed a significant decrease in nocturnal awakenings in acupressure group compared to other two groups.\n The findings of this study indicated that acupressure has an effect on improvement of sleep quality and endorsed it as a non-pharmacological and complementary therapy for sleep-disturbed elderly people.\n Crown Copyright 2009. Published by Elsevier Ltd. All rights reserved.", "Sleep disturbances are a particularly common problem in the elderly. The purpose of this study was to examine the effectiveness of auricular therapy on sleep behaviors in the elderly. One hundred and twenty participants of 60 years old or above and who were suffering from sleep disturbances were invited to participate in this study. Eligible participants were randomly allocated to receive auricular therapy using Junci Medulla (Group A = 30), Semen Vaccariae (Group B = 30) or magnetic pearls (Group C = 60). Groups A and B were the control groups, while Group C was the experimental group. Seven auricular points which are thought to have an effect on promoting sleep were selected. The total treatment course lasted for three weeks. Objective measurement using actigraphic monitoring was performed before the therapy commenced, in the middle period of the therapy, and within one week after the therapy had been completed. After the therapy, there were significant differences among the three groups in terms of the nocturnal sleep time (NST) (F(2,117) = 6.84, p < 0.05) and sleep efficiency (SE) (F(2,117) = 7.69, p < 0.05). Significant improvement in the sleep behaviors was observed in the experimental group using magnetic pearls. In a backward multiple regression, the effect of auricular therapy on SE after allowing for age in female participants is of high statistical significance (F(3,106) = 9.04, p < 0.001). The paper concludes that auricular therapy using magnetic pearls is an effective means of improving the quantity and quality of sleep in the elderly.", "The addition of benzodiazepine hypnotics to a treatment with tricyclic antidepressants has received little systematic study. In a double-blind placebo-controlled design, the effects on mood and on sleep of two benzodiazepine hypnotics (lormetazepam and flunitrazepam) were studied in patients with major depression who were also treated with maprotiline or nortriptyline. After 4 weeks of combined treatment, lormetazepam resulted in a significantly greater decrease in the score on the Hamilton Depression Subscale than placebo, while there was a non-significant trend in favour of lormetazepam in comparison with flunitrazepam. With respect to sleep EEGs, lormetazepam resulted in a significantly greater suppression of REM sleep. The differences between lormetazepam and flunitrazepam may be partly explained by the shorter half-live of lormetazepam.", "A prospective, randomised, single blind, and controlled trial of a hypnotic technique was undertaken in 39 adults with mild to moderate asthma graded for low and high susceptibility to hypnosis. After a six week course of hypnotherapy 12 patients with a high susceptibility score showed a 74.9% improvement (p less than 0.01) in the degree of bronchial hyper-responsiveness to a standardised methacholine challenge test. Daily home recordings of symptoms improved by 41% (p less than 0.01), peak expiratory flow rates improved by 5.5% (p less than 0.01), and use of bronchodilators decreased by 26.2% (p less than 0.05). The improvement in bronchial hyper-reactivity occurred without a change in subjective appreciation of the degree of bronchoconstriction. A control group 17 patients and 10 patients undergoing treatment with low susceptibility to hypnosis had no change in either bronchial hyper-responsiveness or any of the symptoms recorded at home. This study shows the efficacy of a hypnotic technique in adult asthmatics who are moderately to highly susceptible to hypnosis.", "The aim of the study was to evaluate the efficiency of different strategies of intervention to reduce prescription of hypnotics/sedatives in general practice. All 356 general practitioners in the county of Aarhus, Denmark, were divided in three groups. One group received personal information at meetings, another received written material about proper use of hypnotics/sedatives and information about their own prescription rate, and the third group constituted a control group. The prescription rate was recorded before and after the intervention. There was a general decline in the prescription rate recordings, but there were no significant differences between the intervention groups and the control group." ]

[ "9649101", "9916954", "12015496", "7618972", "7650662", "8951516", "8811376", "9494004", "11430967" ]

[ "A randomized controlled trial of early postoperative feeding in gynecologic oncology patients undergoing intra-abdominal surgery.", "Early feeding compared with nasogastric decompression after major oncologic gynecologic surgery: a randomized study.", "A randomized controlled trial of early versus \"traditional\" postoperative oral intake after major abdominal gynecologic surgery.", "Is early oral feeding safe after elective colorectal surgery? A prospective randomized trial.", "Safety and efficacy of early postoperative solid food consumption after cesarean section.", "Early postoperative feeding after elective colorectal surgery is not a benefit unique to laparoscopy-assisted procedures.", "Is early postoperative feeding feasible in elective colon and rectal surgery?", "Early feeding after elective open colorectal resections: a prospective randomized trial.", "Early feeding after cesarean: randomized trial." ]

[ "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.", "To evaluate the feasibility, safety, and tolerance of early feeding in patients undergoing surgery for gynecologic malignancies.\n Patients were stratified according to operative time and type of tumor and were randomized into two arms: A) early oral feeding and B) nasogastric decompression followed by feeding at the first passage of flatus. Variables assessed included nausea, vomiting, time to first passage of flatus and stool, time elapsed before adequate tolerance of a regular diet, postoperative stay, and complications.\n Sixty-one patients were randomized into each arm. The types of tumor, the surgical procedures performed, and the operative times were similar in both groups. Early oral feeding in patients in arm A was associated with a significantly faster resolution of postoperative ileus (P < .01), with a more rapid return to a regular diet (P < .01), with an earlier first passage of stool (P < .01), and with a shorter postoperative stay (P < .05) than patients in arm B. Rates of nausea and vomiting were similar in both arms. Hindered deglutition and nasal soreness caused by the nasogastric tube were observed in 88% of patients in arm B. Insertion of a nasogastric tube was necessary in six patients in arm A (10%), and three of these had postoperative complications. Thus, early feeding was feasible in 95% of patients and did not seem to be related to preoperative chemotherapy, tumor type, or lymphadenectomy.\n Early feeding is feasible and well tolerated and is associated with reduced postoperative discomfort and a more rapid recovery in patients undergoing major surgery for gynecologic malignancies.", "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.", "The routine use of a nasogastric tube after elective colorectal surgery is no longer mandatory. More recently, early feeding after laparoscopic colectomy has been shown to be safe and well tolerated. Therefore, the aim of our study was to prospectively assess the safety and tolerability of early oral feeding after elective \"open\" abdominal colorectal operations.\n All patients who underwent elective laparotomy with either colon or small bowel resection between November 1992 and April 1994 were prospectively randomized to one of the following two groups: group 1: early oral feeding--all patients received a clear liquid diet on the first postoperative day followed by a regular diet as tolerated; group 2: regular feeding--all patients were treated in the \"traditional\" way, with feeding only after the resolution of their postoperative ileus. The nasogastric tube was removed from all patients in both groups immediately after surgery. The patients were monitored for vomiting, bowel movements, nasogastric tube reinsertion, time of regular diet consumption, complications, and length of hospitalization. The nasogastric tube was reinserted if two or more episodes of vomiting of more than 100 mL occurred in the absence of bowel movement. Ileus was considered resolved after a bowel movement in the absence of abdominal distention or vomiting.\n One hundred sixty-one consecutive patients were studied, 80 patients in group 1 (34 males and 46 females, mean age 51 years [range 16-82 years]), and 81 patients in group 2 (43 males and 38 females, mean age 56 years [range 20-90 years]). Sixty-three patients (79%) in the early feeding group tolerated the early feeding schedule and were advanced to regular diet within the next 24 to 48 hours. There were no significant differences between the early and regular feeding groups in the rate of vomiting (21% vs. 14%), nasogastric tube reinsertion (11% vs. 10%), length of ileus (3.8 +/- 0.1 days vs. 4.1 +/- 0.1 days), length of hospitalization (6.2 +/- 0.2 days vs. 6.8 +/- 0.2 days), or overall complications (7.5% vs. 6.1%), respectively, (p = NS for all). However, the patients in the early feeding group tolerated a regular diet significantly earlier than did the patients in the regular feeding group (2.6 +/- 0.1 days vs. 5 +/- 0.1 days; p < 0.001).\n Early oral feeding after elective colorectal surgery is safe and can be tolerated by the majority of patients. Thus, it may become a routine feature of postoperative management in these patients.", "Traditionally patients have received a physician-dictated regimen of gradual expansion of their diets following cesarean section. This has been based upon concern about the possibility of ileus from expanding the diet too rapidly. Given the economic necessity of earlier postoperative discharge following abdominal delivery, many patients have solid food reintroduced in their diets around the time they leave the hospital. This prospective, randomized, controlled study compared a traditional, gradual dietary expansion scheme with patient-determined reintroduction of solid food, which was offered within eight hours of surgery. The hypotheses were that women would eat more rapidly after cesarean section when given the opportunity and that early solid food consumption would reduce the need for analgesia. The results indicated that both hypotheses were correct. Given the opportunity, women will eat solid food very soon after cesarean section (mean +/- SD 10.2 +/- 5.2 hours from surgery to onset of solid food consumption) as compared to women on a traditional dietary expansion regimen (mean +/- SD 41.5 +/- 16.0 hours, P < .001). Women offered food within hours of cesarean section required less patient-requested injectable narcotic postoperatively than did women on gradual dietary expansion (median, 75 mg versus 225 mg meperidine, P < .05). There was no evidence of compromise of safety or comfort from introducing solid food early and allowing the patient to decide when to eat postoperatively. The conclusion from these data is that early postoperative feeding after cesarean section is a safe and effective alternative for most women, who now face early hospital discharge.", "Previous analyses of non-prospectively randomized trials have suggested that early oral postoperative feeding might be a benefit unique to laparoscopic surgery. However, some authors have indicated that early feeding can be tolerated by the majority of patients after elective open surgery.\n This prospective randomized study was undertaken to assess whether the time prior to oral intake of food after laparoscopy-assisted surgery is shorter than that after standard laparotomy.\n This trial included 40 patients who were divided randomly into two groups before operation. Group I included 20 patients (mean age, 52 years; range, 15-77 years) who underwent a laparoscopy-assisted colon or rectal procedure (LAP). Group II consisted of 20 patients (mean age, 56 years, range, 41-74 years) who underwent surgery with a standard midline incision (SMI). On the evening after surgery, patients were allowed clear liquids ab libitum. This regimen was continued until the first postoperative day at which time they could elect to start eating a regular diet. If a patient had two episodes of vomiting, a nasogastric tube was inserted.\n Five laparoscopic procedures were converted to SMI because of adhesions (25%) and an equal number of patients was excluded from the group that was treated in the traditional manner. Therefore, only 30 patients were included in the analysis. There were no deaths in this trial. Complications appeared in four of the patients in the LAP group and in two of the patients in the SMI group (no significant difference). There were no statistically significant differences between the two groups in terms of the ability to tolerate the early oral intake of food, in the frequency of vomiting or in the incidence of insertion of a nasogastric tube. The time to the first bowel movement was 5.4 days in LAP and 5.5 days in SMI, and the difference was not significant.\n This study invalidates the claim by laparoscopic surgeons that earlier oral intake of food is tolerated by their patients than by patients who undergo standard procedures.", "In reports on earlier non-prospectively randomized trials the authors have claimed that early oral postoperative feeding is a unique benefit of laparoscopic surgery. On the other hand, some authors have suggested that early feeding could be tolerated by the majority of patients after elective open surgery.\n This prospective randomized study was undertaken to assess the feasibility and safety of immediate oral feeding in patients subjected to elective open colorectal surgery.\n This trial included 190 patients who underwent an elective colon or rectal operation. Patients were randomized after the operative procedure into one of two groups. Group I (n = 95): On the first evening after the operation, patients were allowed ab libitum intake of clear liquids; this continued until the first postoperative day at which time they progressed to a regular diet as desired. Group II (n = 95): In this group the nasogastric tube was removed when the surgeon considered that postoperative ileus had been resolved.\n Early oral intake was tolerated by 79.6% of the patients in the first 4 days in group I; there were no differences between the two groups from the 4th day on. The incidence of vomiting and nasogastric tube insertion (21.5%) was higher in patients in group I than in those in group II. The time until the first bowel movement was 4.3 days in group I and 4.7 days in group II. Complications appeared in 17.3% of the patients in group I and in 19.3% in group II.\n This study has objectively demonstrated that early oral feeding is feasible and safe in patients who have elective colorectal surgery.", "A period of starvation after colorectal resections to allow for resolution of the clinical evidence of ileus has been an unchallenged surgical doctrine until recent times. A prospective randomized trial comparing early feeding to traditional management in patients undergoing open elective colorectal resections is reported.\n Patients undergoing elective intraperitoneal colorectal resections without stoma formation were randomized to either an early feeding or control group. The early feeding group were allowed free fluids from 4 h postoperatively progressing to a solid diet from the first postoperative day as they tolerated it. The control group remained nil orally until passage of flatus or bowel motion and were then commenced on fluids progressing to solids over 24-48 h.\n There were 40 patients in each group well matched for age, sex, type and duration of operation, method of analgesia and mobilization. Thirty-two patients (80%) in the early feeding group tolerated a diet within 48 h. There was no significant difference in the rate of vomiting, nasogastric reinsertion or complications. The early feeding group tolerated a diet, passed flatus, used their bowels, and were discharged from hospital significantly earlier than the control group.\n Early feeding after elective open colorectal resections is successfully tolerated by the majority of patients, leading to earlier resolution of ileus and hospital discharge.", "To study the rate of ileus symptoms and hospital course of women who are offered solid food shortly after cesarean delivery.\n This study involved women delivered by cesarean under regional anesthesia. Exclusion criteria included general anesthesia, magnesium sulfate, intra-operative bowel injury or bowel surgery, or other conditions that precluded early feeding. Early-fed women were offered regular diets within 8 hours of surgery, and controls were given nothing by mouth for 12-24 hours, advanced to clear liquids on the first postoperative day, and then given solid food on the second or third postoperative day.\n Sixty women were assigned randomly to each method. Early-fed women received solid food sooner after surgery, 5.0 +/- 1.2 hours versus 40.0 +/- 10.6 hours. The incidences of mild ileus symptoms and postoperative complications were similar in both groups; however, the study did not have an adequate sample size to definitively assess safety concerns. Women in the early-fed group had shorter hospital stays (49.5 +/- 12.7 hours versus 75.0 +/- 12.3 hours, P <.001), and shorter time intervals from surgery to bowel movement, 34.5 hours (interquartile range 25.3-48.8) versus 51.0 (43.3-62.0) hours, P <.001. In the early-fed group, women whose operative times exceeded 40 minutes were more likely to have symptoms of mild ileus.\n Early initiation of solid food after cesarean delivery appears to be well tolerated and may be associated with a shorter hospital stay. Early-fed women whose operations exceed 40 minutes may be more likely to have mild ileus symptoms." ]

[ "14581438", "15134985", "9700583", "12215552", "12885803", "12359855", "2462069", "8418243", "17325585" ]

[ "Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer.", "Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer.", "A double blind randomized study of oral clodronate in the treatment of bone metastases from tumors poorly responsive to chemotherapy.", "The PLACORHEN study: a double-blind, placebo-controlled, randomized radionuclide study with (186)Re-etidronate in hormone-resistant prostate cancer patients with painful bone metastases. Placebo Controlled Rhenium Study.", "Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: tandomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate.", "A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma.", "Palliation of painful bone metastases from prostate cancer using sodium etidronate: results of a randomized, prospective, double-blind, placebo-controlled study.", "Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer.", "89Sr versus 153Sm-EDTMP: comparison of treatment efficacy of painful bone metastases in prostate and breast carcinoma." ]

[ "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.", "A Phase III randomized trial was designed to assess the effectiveness of samarium-153 (153Sm)-lexidronam for palliation of bone pain in patients with hormone-refractory prostate cancer.\n A total of 152 men with hormone-refractory prostate cancer and painful bone metastases were enrolled in a prospective, randomized, double-blind trial comparing radioactive (153Sm) versus nonradioactive (152Sm) lexidronam complexes. Patients were randomized (2:1) to the radioactive (153Sm) agent. Patient diaries recording daily pain and analgesic use were completed during a planned 16-week evaluation period. Nonresponders were informed of the treatment received after 4 weeks of treatment and, if initially treated with placebo, were allowed to receive 153Sm-lexidronam in an open-label fashion. Pain was measured using validated patient-derived visual analog scales and pain descriptor scales.\n 153Sm-lexidronam had positive effects on measures of pain relief compared with placebo within 1 to 2 weeks. Reductions in opioid use were recorded at weeks 3 and 4. Because nonresponders were unblinded at week 4, statistical comparisons between the arms beyond week 4 were not possible. Mild, transient bone marrow suppression was the only adverse event associated with 153Sm-lexidronam administration. The mean nadir white blood cell and platelet count (3 to 4 weeks after treatment) was 3800/microL and 127,000/microL, respectively. Counts recovered to baseline after approximately 8 weeks. No grade 4 decreases in either platelets or white bloods cells were documented.\n These findings demonstrate that 1 mCi/kg 153Sm-lexidronam is both safe and effective for the palliation of painful bone metastases in patients with hormone-refractory prostate cancer.", "Bisphosphonates are used in oncology as a means of decreasing complications due to bone metastases, in association with anticancer treatment, especially in patients with breast cancer, prostate cancer and myeloma. Little is known about the effects of bisphosphonates on bone metastases from other tumors and in particular from tumors for which no effective treatment is available. We conducted a randomized, double-blind placebo-controlled trial of oral clodronate in patients with bone metastases from tumors poorly responsive to chemotherapy, with the aims of evaluating the effects of this drug on symptoms control and bone metastases evolution. Sixty-six patients with poorly responsive tumors such as non-small cell lung cancer (NSCLC), bladder cancer, gastrointestinal cancers, kidney cancer, melanoma and metastatic carcinoma of unknown origin entered the study. Patients were randomized to receive either clodronate 1,600 mg/day for one year or identical placebo-containing tablets. Various parameters such as Karnofsky performance status, pain score (measured by a visual-analogue scale) and analgesic requirement were recorded at monthly intervals. Of the 66 patients enrolled, 9 were observed for one month or less; 7 were followed for two months; only 50 patients were followed for more than 2 months and could be adequately evaluated. At 3 months both clodronate and placebo-treated patients had a decrease in Karnofsky performance status, with the decrease being more evident in the placebo group. Mean pain scores showed an increase of pain in patients receiving placebo and a decrease of pain in patients receiving clodronate, although the difference failed to be statistically significant. Analgesics requirement increased in both groups, but significantly more in patients receiving placebo (p = 0.042), in whom increase in opioid requirements was particularly evident. Toxicity was low, with occasional gastroenteric discomfort in both groups. The main problem of this study was the difficulty in recruiting an adequate number of patients and following them for a sufficient period of time: general conditions rapidly deteriorated in many patients, and approximately 25% of the 66 enrolled were not considered evaluable; few patients survived for the length of the study, one year. This might partly account for the lack of significance of some of the parameters under study. With these limits, oral clodronate demonstrated some efficacy in symptom control and in reducing the need for analgesics.", "(186)Re-1,1-hydroxyethylidene diphosphonate (etidronate) can be used for the palliative treatment of metastatic bone pain. A randomized, placebo-controlled study using (186)Re-etidronate was conducted on end-stage prostate cancer patients with metastatic bone pain.\n Pain relief was assessed using an electronic diary containing questions reflecting the multidimensional character of chronic pain. The diary was marked twice daily for a maximum of 14 wk (2 wk before and 12 wk after the injection). Pain response was determined using a specific decision rule in which pain intensity, medication index, and daily activities were the core determinants. A positive response day was defined as a day on which pain intensity was reduced > or = 25% compared with baseline values, while medication index and daily activities were at least constant, or on which pain intensity was reduced < 25% and medication index or daily activities improved > or = 25%, without worsening of the remaining factor. The total response (%) was defined as the number of positive response days divided by the number of days of follow-up.\n Of the 111 included patients, 79 were evaluable (43 (186)Re-etidronate, 36 placebo). Thirty-two patients were excluded from the analysis because of incomplete datasets. The total response of the patients treated with (186)Re-etidronate varied from 0% to 96% (mean, 27%, or 23/84 d). In the placebo group, the total response varied from 0% to 80% (mean, 13%, or 11/84 d; Mann-Whitney U test, P < 0.05). The number of patients who requested radiotherapy was higher in the placebo group (67%) than in the (186)Re-etidronate group (44%) (relative risk, 1.51; Fisher's exact test, P = 0.069).\n This randomized controlled trial confirmed that, compared with placebo, (186)Re-etidronate resulted in a significantly longer pain response in the treatment of bone pain from metastasized prostate cancer.", "We investigated the effect of repeated bone-targeted therapy with rhenium-188 hydroxyethylidenediphosphonate (HEDP) in patients with progressive, hormone-resistant prostate carcinoma and bone pain. The aim of this study was to determine the pain palliation and the antitumor effect of rhenium-188 HEDP treatments.\n Sixty-four patients were randomly assigned to one of two groups for radionuclide therapy with rhenium-188 HEDP; patients of group A received a single injection, patients of group B received two injections (interval, 8 weeks). After therapy, patients were followed-up by assessment of pain palliation and clinical outcome until death.\n In both groups, toxicity was low, with moderate thrombopenia and leukopenia (maximum common toxicity criteria grade of 2). The effectiveness of rhenium-188 HEDP for pain palliation was better in the repeated treatment group (group B), with a response rate and time of response of 92% and 5.66 months, respectively (P =.006 and P =.001). In group B, 11 (39%) of 28 patients had a prostate-specific antigen decrease of more than 50% for at least 8 weeks, compared with two (7%) of 30 patients in the single-injection group (group A). The median times to progression of group A and group B were 2.3 months (range, 0 to 12.2 months) and 7.0 months (range, 0 to 24.1 months), respectively (P =.0013), and the median overall survival times were 7.0 months (range, 1.3 to 36.7 months) and 12.7 months (range, 4.1 to 32.2 months), respectively (P =.043).\n Compared with single-injection therapy, repeated bone-targeted therapy with rhenium-188 HEDP administered to patients with advanced progressive hormone-refractory prostate carcinoma enhanced pain palliation and improved progression-free and overall survival. Larger studies are justified to further evaluate the use of rhenium-188 HEDP.", "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.", "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.", "Osteolytic metastases often give rise to hypercalcemia, fracture, and bone pain, and occur commonly in patients with recurrent breast cancer. We assessed the bisphosphonate, clodronate, which has proven to be a useful treatment for hypercalcemia and may be a potent inhibitor of tumor-induced osteolysis, for its effect on reducing the osseous complications of metastatic breast cancer.\n We studied 173 patients with bone metastases due to breast cancer in a randomized, double-blind, placebo-controlled trial of oral clodronate 1,600 mg/d (85 patients) compared with an identical placebo (88 patients).\n The patients in each wing were comparable in their clinical, radiologic, and biochemical characteristics at trial entry. In patients who received clodronate, there was a significant reduction compared with placebo in the total number of hypercalcemic episodes (28 v 52; P < .01), in the number of terminal hypercalcemic episodes (seven v 17; P < .05), in the incidence of vertebral fractures (84 v 124 per 100 patient-years; P < .025), and in the rate of vertebral deformity (168 v 252 per 100 patient-years; P < .001). The combined rate of all morbid skeletal events was significantly reduced (218.6 v 304.8 per 100 patient-years; P < .001). Trends were seen in favor of clodronate for nonvertebral fracture rates and radiotherapy requirements for bone pain (particularly spinal pain). No significant survival differences and no significant differences in side effects were observed between the two groups.\n These findings indicate that oral clodronate has a beneficial effect on the skeletal morbidity associated with breast cancer and should be considered as antiosteolytic therapy in affected patients. It deserves further investigation as an adjuvant therapy in operable breast cancer and in patients with nonosseous recurrence who are at high risk for bone metastases.", "Painful bone metastases are most frequent in patients with advanced prostate or breast carcinoma. The aim of this study was to compare the analgesic effect of radionuclide therapy using Sr and Sm-EDTMP in patients with painful bone metastases of these tumours.\n One hundred patients treated with radionuclide bone palliation therapy were analysed. The study population consisted of 60 male patients with advanced prostate carcinoma and 40 female patients with advanced breast carcinoma. Fifty patients (30 men and 20 women) were treated with Sr (150 MBq). The other 50 patients were treated with Sm-EDTMP (37 MBq x kg). The treatment efficacy was evaluated by a visual analogue scale (VAS), Karnofsky performance scale, and dosage of analgesic drugs used.\n Complete pain relief was found in 40% of women and 40% of men treated using Sm-EDTMP and in 25% of women and 33% of men treated with Sr. No analgesic effect occurred in 20% of patients. A better analgesic effect was found in cases of osteoblastic metastases compared to mixed metastases. Statistically significant reduction of pain intensity, use of analgesic drugs and improvement of performance in Karnofsky scale was found in cases of both radionuclides.\n The analgesic effects of Sr and Sm-EDTMP was similar in both prostate and breast carcinoma. However, the effect was dependent on the type of metastases; better response was observed in cases of osteoblastic metastases than in patients with mixed metastases. Severe adverse reactions after this therapy were rare." ]

[ "16555167", "11434406", "7498868", "10591711", "15605620", "15538592", "23196026", "10759336", "10823363" ]

[ "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.", "Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trial.", "[Treatment of depressive symptoms with a high concentration hypericum preparation. A multicenter placebo-controlled double-blind study].", "Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks.", "Efficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: a double-blind, randomized, placebo-controlled clinical trial.", "Hypericum extract LI 160 and fluoxetine in mild to moderate depression: a randomized, placebo-controlled multi-center study in outpatients.", "Clinical significance of hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities.", "Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression.", "Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study." ]

[ "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.", "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.", "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.", "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 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.", "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.", "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.", "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.", "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." ]

[ "8201703", "9171752", "21557814", "1572460", "15798610", "1913123", "2310658", "8351363", "8776642" ]

[ "A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia.", "Prospective randomized trial of high-dose bolus versus low-dose tissue plasminogen activator infusion in the management of acute limb ischaemia. Thrombolysis Study Group.", "SYNTHESIS expansion: design of a nonprofit, pragmatic, randomized, controlled trial on the best fast-track endovascular treatment vs. standard intravenous alteplase for acute ischemic stroke.", "Surgical treatment versus thrombolysis in acute arterial occlusion: a randomised controlled study.", "Comparison of intravenous and intra-arterial urokinase thrombolysis for acute ischaemic stroke.", "Randomized trial of intra-arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra-arterial streptokinase in peripheral arterial thrombolysis.", "Investigation of intravascular haemolysis during treatment of acute stroke with intravenous glycerol.", "Intraarterial thrombolysis of lower extremity occlusions: prospective, randomized comparison of forced periodic infusion and conventional slow continuous infusion.", "The role of the protein C-thrombomodulin system and fibrinolysis during cardiovascular surgery: influence of acute preoperative plasmapheresis." ]

[ "Despite the widespread use of intraarterial thrombolytic therapy for peripheral arterial occlusive disease, a randomized study comparing its efficacy with that of operative intervention has never been performed. This study evaluates the potential of intraarterial urokinase infusion to provide clinical benefits in patients with acute peripheral arterial occlusion.\n Patients with limb-threatening ischemia of less than 7 days' duration were randomly assigned to intraarterial catheter-directed urokinase therapy or operative intervention. Anatomic lesions unmasked by thrombolysis were treated with balloon dilation or operation. The primary end points of the study were limb salvage and survival.\n A total of 57 patients were randomized to the thrombolytic therapy group, and 57 patients were randomized to the operative therapy group. Thrombolytic therapy resulted in dissolution of the occluding thrombus in 40 (70%) patients. Although the cumulative limb salvage rate was similar in the two treatment groups (82% at 12 months), the cumulative survival rate was significantly improved in patients randomized to the thrombolysis group (84% vs 58% at 12 months, p = 0.01). The mortality differences seemed to be primarily attributable to an increased frequency of in-hospital cardiopulmonary complications in the operative treatment group (49% vs 16%, p = 0.001). The benefits of thrombolysis were achieved without significant differences in the duration of hospitalization (median 11 days) and with only modest increases in hospital cost in the thrombolytic treatment arm (median $15,672 vs $12,253, p = 0.02).\n Intraarterial thrombolytic therapy was associated with a reduction in the incidence of in-hospital cardiopulmonary complications and a corresponding increase in patient survival rates. These benefits were achieved without an appreciable increase in the duration of hospitalization and with only modest increases in hospital cost, suggesting that thrombolytic therapy may offer a safe and effective alternative to operation in the initial treatment of patients diagnosed with acute limb-threatening peripheral arterial occlusion.", "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.", "Rationale Reperfusion in ischemic stroke can be pursued by either systemic intravenous thrombolysis or endovascular treatment. However, systemic intravenous thrombolysis with alteplase within 4·5 h of symptom onset in selected patients is the only medication of proven efficacy. No randomized-controlled trials have so far compared the two modalities. To explore this, after a pilot phase, we started the SYNTHESIS Expansion trial. Aims To determine whether endovascular treatment (i.e., intra-arterial thrombolysis with alteplase - if necessary, associated to or substituted by mechanical clot disruption and/or retrieval) compared with systemic intravenous thrombolysis with alteplase, administered according to European labelling, increases the proportion of independent survivors at three-months. Design SYNTHESIS Expansion is an open-label, multicenter randomized-controlled trial, with blinded follow-up. Eligibility applies to; patients with symptomatic ischemic stroke, seen within 4·5 h of onset; being able to initiate intravenous alteplase immediately, and endovascular treatment as soon as possible (not later than six-hours of stroke onset). The study is pragmatically based on the 'uncertainty principle' between endovascular treatment and systemic intravenous thrombolysis for patients eligible for intravenous alteplase. There are no prespecified clinical or instrumental criteria to further select a patient, although investigators are left free to use them. Enrollment will be completed with 350 randomized patients. Primary analysis is on an intent-to-treat basis. Study outcomes Primary: modified Rankin scale score of 0 or 1 at three-months. Secondary: neurological deficit seven-days after thrombolysis and the safety of the procedure on the basis of events reported within seven-days following thrombolysis - symptomatic cerebral hemorrhage, fatal and nonfatal stroke, death from any cause, neurological deterioration.\n © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.", "Thrombolytic treatment has been tried in various forms for acute limb ischaemia with varying degrees of success but is also often accompanied by bleeding problems. The present investigation compares the effect of surgical thrombectomy (TE) and thrombolysis (TL) using recombinant tissue plasminogen activator (rt-PA). Twenty patients with a need for intervention owing to ischaemia lasting more than 24 h but less than 14 days were included. Patients randomised to TE were operated under epidural anaesthesia and patients in the TL group received 30 mg rt-PA during a 3 h period through a catheter placed into the thrombus and advanced as lysis was achieved. Thrombectomy resulted in an immediate restitution of blood flow in six out of nine cases, in three cases a bypass procedure was performed, and one of these failed with a resultant amputation. Thrombolysis gave a good primary result in six cases which lasted in four of them. Three had a subsequent percutaneous transluminal angioplasty. Partial lysis was seen in two cases and a further two failed. Five went to surgery with three bypass and two fogarty procedures being necessary. There was no hospital mortality and there were no bleeding complications due to the rt-PA treatment in this series. In 19 out of 20 patients the circulation was re-established. Appropriate handling of acute ischaemic conditions implies the use of both thrombolysis and appropriate surgical procedures, including distal bypass grafts.", "Intravenous fibrinolysis (IVF) with rt-PA (alteplase) provides significant benefits in acute ischaemic stroke when it is given within the first three hours following stroke onset. Intra-arterial fibrinolysis (IAF) with pro-urokinase in PROACT II study provides quite the same benefit in the first 6 hours. IVF and IAF have never been compared. To compare the efficacy and safety of IVF and IAF with urokinase given within the first 6 hours of acute ischaemic stroke. Patients fulfilling the selection criteria were randomly assigned to receive urokinase 900,000 units via intravenous or intra-arterial routes. This randomised monocentre study was done between December 1995 and August 1997. The primary outcome was defined as the number of patients with a modified Rankin score of 2 or less. Secondary outcomes included mortality, frequency of symptomatic intracranial haemorrhage (SIH), neurological and functional scores. Fourteen patients were given IVF and 13 IAF. The study was terminated by the National Health Authorities when 27 patients had been included because of the mortality rate. Seven patients (26%) died, 4 in the IV group (oedematous infarct in 3 and recurrence in 1), 3 in the IA group (SIH in 2, and oedematous infarct in 1). Patients given IVF were treated significantly earlier (4:16 h vs 5:24 h; p=.007). Although IA patients showed greater and earlier improvement there was no significant difference in primary and secondary outcomes. Because of premature termination, the trial was too small to provide any reliable and conclusive results. Intra-arterial fibrinolysis began significantly later than IV fibrinolysis but it gave non-significantly better results in this prematurely terminated study.", "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.", "1. In patients with acute strokes entering a large ongoing randomised double-blind controlled trial of intravenous glycerol therapy, the extent and pathogenesis of any ensuing haemolysis were evaluated using standard clinical investigations and in vitro techniques. 2. Twenty patients received 10% glycerol in saline (500 ml over 4 h on 6 consecutive days) and 15 received corresponding control treatment with saline. 3. Intravascular haemolysis was evident after the first infusion; compared with the controls the glycerol group had i) a greater mean reduction in serum haptoglobin concentration (P less than .05), and ii) a greater proportion exhibiting haemoglobinaemia (P = 0.03). 4. After 6 days of glycerol treatment, the mean reduction in haemoglobin concentration was only 0.8 g more than in controls; this difference being neither clinically nor statistically significant. 5. Glycerol therapy was not associated with haemoglobinuria, renal insufficiency or disseminated intravascular coagulation. 6. Exposure of red blood cells to 1-10% glycerol in vitro did not induce haemolysis per se; on re-exposure to lower concentrations lysis ensued provided a minimum osmotic gradient was present. 7. Whilst taking standard dosage regimes of glycerol, the stroke patients we studied manifested a degree of intravascular haemolysis but its consequences were not clinically significant; lysis probably ensued after venous blood acquiring high glycerol concentrations mixed with blood containing little or no glycerol.", "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 assess the benefits of withdrawn autologous plasma, the objective of this study was to investigate whether withdrawal of acutely performed platelet-rich or platelet-poor plasmapheresis allays changes in the protein C-thrombomodulin and fibrinolytic systems after retransfusion secondary to cardiopulmonary bypass (CPB). In addition, the study attempted to determine the influence of acute plasmapheresis (APP) on the protein C-thrombomodulin and fibrinolytic systems as well as on homologous blood consumption and perioperative blood loss in elective aortocoronary bypass patients.\n The investigation was scheduled as a prospective, randomized, unblinded study.\n This single investigation was conducted in the Department of Anesthesiology and Intensive Care Medicine at a university in Germany. The study protocol was approved by the Ethics Committee of the hospital, and informed consent was obtained.\n Sixty male patients scheduled for elective coronary artery bypass grafting with extracorporeal circulation were included in the study.\n APP was performed between induction of anesthesia and incision, collecting either 10 mL/kg of autologous platelet-poor plasma (PPP patients, group 1; n = 20) or the same amount of platelet-rich plasma (PRP patients, group 2; n = 20). Patients of group 3 (n = 20) had no APP (control group). All patients were maintained on their usual regimen of cardiac drugs until the morning of surgery. To preserve hemodynamic stability and restore the intravascular oncotic pressure, the separated plasma was replaced by infusion of an equal amount of hydroxyethyl starch solution (HES) (6% HES, molecular weight 2 x 10(5), substitution rate 0.5%). In all operations, the same surgical procedure was chosen. For all patients, induction and maintenance of anesthesia were similar, consisting of weight-related doses of fentanyl (35 micrograms/kg), midazolam (0.65 mg/kg), and pancuronium bromide (0.15 mg/kg). The lungs of all patients were mechanically ventilated during the first 5 hours after the end of the operation.\n All patients had serial coagulation studies including antithrombin (AT) III-activity, prekallikrein, factor XII, and immunologic tests such as thrombin-antithrombin III (TAT), fibrinopeptide A (FPA), protein C and S (PC and PS), thrombomodulin (TM), tissue-plasminogen-activator (t-PA), plasminogen-activator-inhibitor (PAI 1), fibrinopeptide B beta 15-42 (FPB beta 15-42), D-dimers, and hemoglobin and platelet counts determined intraoperatively and postoperatively. Chest tube drainage and transfusion requirements were recorded. APP had no negative effects on the quality of PPP and PRP plasma. The platelet count of the withdrawn plasma was 28 +/- 12 x 10(9)/L (PPP group) and 245 +/- 36 x 10(9)/L (PRP group). At the end of the operation (after retransfusion of autologous plasma) and on the morning of the first postoperative day, platelet counts were significantly higher (p > 0.05) in the PRP than in the PPP and control groups. Plasma concentrations of TAT and FPA increased (ranging from +185% to +340% from baseline values) and AT III-activity, PC, PS, and TM antigen decreased (ranging from -8% to -55% from baseline values) to a different extent for all three groups throughout CPB. t-PA-activity increased with a maximum at the end of CPB (PPP group, 6.9 +/- 1.5 IU/mL: PRP group, 3.8 +/- 0.8 IU/mL; control group, 10.9 +/- 2.8 IU/mL). Fibrin and fibrinogen degradation markers such as D-dimers and FPB beta 15 to 42 occurred in peak concentrations after neutralization of heparin by protamine. Only PRP patients showed baseline concentrations of coagulation parameters the next morning (p < 0.05). Total postoperative blood loss within the first 24 hours reached 482 +/- 273 mL (PRP group), 775 +/- 256 mL (PPP group), and 948 +/- 342 mL in the control group (p < 0.05).(ABSTRACT TRUNCATED)" ]

[ "19058760", "9297994", "2861311", "18378519", "2864374", "490882", "9635947", "20166337", "2911834" ]

[ "Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial.", "Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.", "Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial.", "Treatment of hypertension in patients 80 years of age or older.", "Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). The IPPPSH Collaborative Group.", "Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group.", "Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group.", "Improving combined diabetes outcomes by adding a simple patient intervention to physician feedback: a cluster randomized trial.", "Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study." ]

[ "Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for lowering blood pressure in patients who have had a stroke.\n Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure [SBP] >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008.\n 179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5-16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome--death or dependency at 2 weeks--occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1.03, 95% CI 0.80-1.33; p=0.82). There was no evidence of early neurological deterioration with active treatment (RR 1.22, 0.33-4.54; p=0.76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17-25] mm Hg vs 11 [5-17] mm Hg; p=0.004). No increase in serious adverse events was reported with active treatment (RR 0.91, 0.69-1.12; p=0.50) but 3-month mortality was halved (9.7%vs 20.3%, hazard ratio [HR] 0.40, 95% CI 0.2-1.0; p=0.05).\n Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed.", "Isolated systolic hypertension occurs in about 15% of people aged 60 years or older. In 1989, the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension. Fatal and non-fatal stroke combined was the primary endpoint.\n All patients (> 60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160-219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10-40 mg daily, with the possible addition of enalapril 5-20 mg daily and hydrochlorothiazide 12.5-25.0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat.\n At a median of 2 years' follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n = 2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n = 2398). The between-group differences were systolic 10.1 mm Hg (95% CI 8.8-11.4) and diastolic, 4.5 mm Hg (3.9-5.1). Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years (42% reduction; p = 0.003). Non-fatal stroke decreased by 44% (p = 0.007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p = 0.03). Non-fatal cardiac endpoints decreased by 33% (p = 0.03) and all fatal and non-fatal cardiovascular endpoints by 31% (p < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, p = 0.07), but all-cause mortality was not influenced (-14%; p = 0.22).\n Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints.", "A double-blind randomised placebo-controlled trial of antihypertensive treatment was conducted in patients over the age of 60. Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range 90-119 mm Hg and a systolic pressure in the range 160-239 mm Hg. 840 patients were randomised either to active treatment (hydrochlorothiazide + triamterene) or to matching placebo. If the blood pressure remained raised, methyldopa was added to the active regimen and matching placebo in the placebo group. An overall intention-to-treat analysis, combining the double-blind part of the trial and all subsequent follow-up, revealed a non-significant change in total mortality rate (-9%, p = 0.41) but a significant reduction in cardiovascular mortality rate (-27%, p = 0.037). The latter was due to a reduction in cardiac mortality (-38%, p = 0.036) and a non-significant decrease in cerebrovascular mortality (-32%, p = 0.16). In the double-blind part of the trial, total mortality rate was not significantly reduced (-26%, p = 0.077). Cardiovascular mortality was reduced in the actively treated group (-38%, p = 0.023), owing to a reduction in cardiac deaths (-47%, p = 0.048) and a non-significant decrease in cerebrovascular mortality (-43%, p = 0.15). Deaths from myocardial infarction were reduced (-60%, p = 0.043). Study-terminating morbid cardiovascular events were significantly reduced by active treatment (-60%, p = 0.0064). Non-terminating cerebrovascular events were reduced (-52%, p = 0.026), but the non-terminating cardiac events were not (+3%, p = 0.98). In the patients randomised to active treatment there were 29 fewer cardiovascular events and 14 fewer cardiovascular deaths per 1000 patient years during the double-blind part of the trial.", "Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death.\n We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.\n The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001).\n The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 [ClinicalTrials.gov].).\n Copyright 2008 Massachusetts Medical Society.", "Myocardial infarction, sudden cardiac death, cerebrovascular accidents, blood pressure control and treatment tolerability were studied in a randomized double-blind trial conducted in 6357 men and women aged 40-64 years with uncomplicated essential hypertension (diastolic blood pressures 100-125 mmHg). At the start of the trial 3185 patients received treatment based on a beta-blocker (oxprenolol), while in the remaining 3172 placebo replaced oxprenolol. Supplementary drugs, excluding beta-blockers, were used as necessary in both treatment groups, with the aim of reducing diastolic pressure to 95 mmHg or less. Patients were followed for 3-5 years, a total of 25 651 patient years at risk. In most respects the two groups fared equally well; sudden death (relative risk [RR] 1.08; 95% confidence interval [Cl] 0.68 and 1.72), myocardial infarction (RR 0.83; Cl 0.59 and 1.16) and cerebrovascular accident (RR 0.97; Cl 0.64 and 1.47) rates were similar. Beta-blocker based therapy was associated with significantly lower average blood pressures, earlier ECG normalization, less hypokalaemia and fewer withdrawals from double-blind treatment for uncontrolled hypertension. Doctor-elicited and patient-assessed unwanted effects demonstrated overall good tolerability. In smokers the cardiac event rate was doubled. We propose that beta-blocker treatment effects depend on smoking status, with a significant interaction benefiting non-smoking men. Lower blood pressures during treatment were associated with substantially lower rates for cardiac as well as cerebrovascular events. Proportional hazards analysis also underlines the importance of other cardiovascular risk factors. The IPPPSH stresses the need for a comprehensive approach to the management of blood pressure and other risk factors in hypertensive patients.", "The Hypertension Detection and Follow-up Program (HDFP), in a community-based, randomized controlled trial involving 10,940 persons with high blood pressure (BP), compared the effects on five-year mortality of a systematic antihypertensive treatment program (Stepped Care [SC]) and referral to community medical therapy (Referred Care [RC]). Participants, recruited by population-based screening of 158,906 people aged 30 to 69 years in 14 communities througout the United States, were randomly assigned to SC or RC groups within each center and by entry diastolic blood pressure (DBP) (90 to 104, 105 to 114, and 115 + mm Hg). Over the five years of the study, more than two thirds of the SC participants continued to receive medication, and more than 50% achieved BP levels within the normotensive range, at or below the HDFP goal for DBP. Controls of BP was consistently better for the SC than for the RC group. Five-year mortality from all causes was 17% lower for the SC group compared to the RC group (6.4 vs 7.7 per 100, P less than .01) and 20% lower for the SC subgroup with entry DBP of 90 to 104 mm Hg compared to the corresponding RC subgroup (5.9 vs 7.4 per 100, P less than .01). These findings of the HDFP indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large numbers of people with high BP in the population, including those with \"mild\" hypertension.", "Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension.\n 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo.\n Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001).\n Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.", "Research on synergistic effects of patient targeted interventions combined with physician-targeted interventions has been limited.\n To compare a combined physician-patient intervention to physician feedback alone on a composite outcome of glycemic, lipid and blood pressure control.\n In this cluster study 417 patients with adult-type 2 diabetes from four primary care clinics were randomized to receive either a physician-only intervention or a combined physician-plus-patient intervention. Physicians in all clinics received diabetes-related quality performance feedback during staff meetings. Patients at combined-intervention clinics also received a letter encouraging them to remind their doctors to address essential aspects of diabetes care at the next visit. At 1 year follow-up, outcome measurements included hemoglobin A1c, low density lipoprotein-cholesterol and systolic blood pressure: namely, the proportion of patients with HbA1c 9%, LDL <130 mg/dl and SBP <140 mmHg both as separate outcomes and combined.\n After adjusting for patient characteristics and baseline measures, follow-up levels of HbA1c (7.5% vs. 7.8%, P = 0.09), LDL (104.7 vs. 110.7 mg/dl, P < 0.05) and SBP (135.6 vs. 139.9, P = 0.10) were marginally better for combined-intervention patients compared to physician-only intervention patients. Significantly more patients in the combined-intervention (38.8%) than physician-only intervention (24.2%) met all three targets (HbA1c (9%, LDL (130 mg/dl and SBP <140 mmHg) as a single combined outcome (adjusted odds ratio 2.4, P < .01).\n Compared to physician-feedback alone, a dual intervention combining a patient letter with physician feedback produced modest improvements in glycemic, lipid and blood pressure control individually, but substantial improvement in a combined measure of these three outcomes together. Using composite outcomes may detect meaningful improvements in the management of complex chronic disease.", "The pilot study of the Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension. It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months. Mean age of the participants was 72 years; 63% were women, and 82% were white. Pretreatment blood pressures averaged 172/75 mm Hg. Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication. Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups, respectively, with 60% and 33% of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit. All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk, and rates for definite \"first stroke\" were 8.3 and 12.8 per 1,000 years of risk. Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates. A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates." ]

[ "2594037", "2934438", "6175137", "3579357", "9071622", "20889234", "16518424", "14567368", "8070287" ]

[ "A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides.", "Intralesional interferon in the treatment of early mycosis fungoides.", "Transfer factor therapy in mycosis fungoides: a double-blind study.", "Recombinant interferon alfa-2b in plaque-phase mycosis fungoides. Intralesional and low-dose intramuscular therapy.", "A randomized clinical trial of topical paromomycin versus oral ketoconazole for treating cutaneous leishmaniasis in Turkey.", "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.", "A prospective, double-blind phase II study evaluating the safety and efficacy of a topical histamine gel for the prophylaxis of oral mucositis in patients post hematopoietic stem cell transplantation.", "Ciclopirox gel in the treatment of patients with interdigital tinea pedis.", "A double-blind, vehicle-controlled study of the safety and efficacy of Fungoid Tincture in patients with distal subungual onychomycosis of the toes." ]

[ "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.", "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.", "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.", "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.", "An open-labeled, randomized clinical trial to evaluate the efficacy of paromomycin ointment as compared with ketoconazole was conducted on seventy-two patients of both sexes and different ages with the confirmed diagnosis of cutaneous leishmaniasis (CL). All patients had a complete clinical evaluation for other diseases. Patients were excluded if they were pregnant or nursing or if they had serious concomitant diseases. Patients were divided randomly into two treatment groups: in the first group 40 patients were treated with an ointment containing 15% paromomycin sulfate and 12% methylbenzothonium chloride in white soft paraffin (labeled as p-ointment by El-On1) twice daily for 15 days. Treated lesions were left uncovered. The second group consisted of 32 patients who received ketoconazole 400 mg/day orally for 30 days. This dosage was reduced to 200 mg/day for patients below 12 years of age. In all cases the diagnosis was based on positive smear and/or culture. Direct smears were prepared from the exudate obtained by a small incision made at the edge of the lesion with a sterile surgical blade or lancet and stained using the Giemsa method for leishmania bodies (Fig 1). In smear negative and suspected cases aspirates taken by puncturing the lesions were inoculated onto NNN (Novy, McNeal, Nicolle) medium for culture. The cultures were incubated at 28 degrees C and the development of motile promastigotes was observed. Clinical and parasitological evaluations of the patients were performed at the end of the treatment period and 4 weeks post-treatment. A cure was defined as complete healing and disappearance of the lesion or reversible hypopigmentation at the site of lesion. Incomplete or partial improvement was defined as a reduction in the size of a lesion and the absence of parasites on smear or culture. A treatment failure was defined as the absence of any changes in the lesion and persistence of parasites on smear or culture.", "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.", "The aim of this study was to evaluate the safety, tolerability and efficacy of a topical gel containing histamine dihydrochloride (HDC) versus a placebo gel in preventing oral mucositis in hematopoietic stem cell transplantation (HSCT) patients. A total of 45 patients post-HSCT were enrolled in a prospective longitudinal, placebo-controlled, double-blind study. Patients were evaluated twice weekly for oral mucositis (OMAS, NCI score), oral pain (VAS), oral function and salivary flow rate. Compliance was assessed using a patient diary. Oral mucositis developed in 85% of the HDC group and 63% of the placebo group. The mean maximal intensity for NCI score was 1.45+/-1 in the HDC group and 1.21+/-1.27 in the placebo group (P=0.37). The mean duration of oral mucositis was 4.7+/-3.6 and 2.33+/-2.23 days in the HDC and placebo groups, respectively (P=0.06). The same trends were measured with OMAS. Visual analogue scale for oral pain and oral function was not significantly different between the two groups. Histamine dihydrochloride was found to be safe. In the search for topical agents for the prevention of mucositis, we found that HDC neither improves nor worsens oral mucositis in HSCT patients. The balance between the pro- and anti-inflammatory effects of HDC should be investigated further in order to acquire a clinically effective topical medication based on its anti-inflammatory properties.", "BACKGROUND Tinea pedis (athlete's foot) is the most common fungal infection in the general population. Ciclopirox, a broad-spectrum hydroxypyridone antifungal, has proven efficacy against the organisms commonly implicated in tinea pedis; Trichophyton rubrum, T.mentagrophytes and Epidermophyton floccosum.\n Two multicenter, double-blind, clinical studies compared the efficacy and safety of ciclopirox gel with that of its vehicle base in subjects with moderate interdigital tinea pedis with or without plantar involvement.\n Three hundred and seventy-four subjects were enrolled and randomized to one of two treatment groups: ciclopirox gel 0.77%, or ciclopirox gel vehicle, applied twice daily for 28 days, with a final visit up to day 50. The primary efficacy variable was Treatment Success defined as combined mycological cure and clinical improvement >/= 75%. Secondary measures of effectiveness were Global Clinical Response, Sign and Symptom Severity Scores, Mycological Evaluation (KOH examination and final culture result), Mycological Cure (negative KOH and negative final culture results) and Treatment Cure (combined clinical and mycological cure).\n At endpoint (final post-baseline visit), 60% of the ciclopirox subjects achieved treatment success compared to 6% of the vehicle subjects. At the same time point, 66% of ciclopirox subjects compared with 19% of vehicle subjects were either cleared or had excellent improvement. Pooled data showed that 85% of ciclopirox subjects were mycologically cured, compared to only 16% of vehicle subjects at day 43, 2 weeks post-treatment.\n Ciclopirox gel 0.77% applied twice daily for 4 weeks is an effective treatment of moderate interdigital tinea pedis due to T. rubrum, T. mentagrophytes and E. floccosum and is associated with a low incidence of minor adverse effects.", "Onychomycosis is one of the most common causes of nail disease and one of the hardest to treat among fungal infections. A double-blind, vehicle-controlled study has been conducted to evaluate the safety and efficacy of Fungoid Tincture (Pedinol Pharmacal, Inc), for the treatment of fungal infection of the toenails. Ten patients with distal subungual onychomycosis were treated for twelve months with topical Fungoid Tincture. Another ten patients with the same ailment were treated with the vehicle alone. Once a month, clinical and global evaluation of the target nail was done, in addition to trimming and debridement of the nails. After twelve months of treatment, 90 percent of patients applying Fungoid Tincture showed negative results on culture. There were minimal adverse effects." ]

[ "6143340", "6437366", "15994710", "9004053", "6810839", "15056579", "7897085", "7811160", "10807488" ]

[ "Continuation therapy with lithium and amitriptyline in unipolar depressive illness: a randomized, double-blind, controlled trial.", "Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Report of the NIMH Collaborative Study Group comparing lithium carbonate, imipramine, and a lithium carbonate-imipramine combination.", "Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial.", "Gradual discontinuation of lithium augmentation in elderly patients with unipolar depression.", "Lithium carbonate and imipramine in the prophylaxis of unipolar and bipolar II illness: a prospective, placebo-controlled comparison.", "Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone.", "A 24-month follow-up study of unipolar subjects: a comparison between lithium and fluvoxamine.", "Pharmacotherapy of impaired affect in recovering schizophrenic patients.", "A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group." ]

[ "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.", "In a double-blind, long-term follow-up study, 117 bipolar patients received lithium carbonate, imipramine hydrochloride, or both and 150 unipolar patients received lithium carbonate, imipramine, both lithium carbonate and imipramine, or placebo. With bipolar patients, lithium carbonate and the combination treatment were superior to imipramine in preventing manic recurrences and were as effective as imipramine in preventing manic recurrences and were as effective as imipramine in preventing depressive episodes. The combination treatment provided no advantage over lithium carbonate alone. With unipolar patients, imipramine and the combination treatment were more effective than lithium carbonate and placebo in preventing depressive recurrences. The combination treatment provided no advantage over imipramine alone. The lithium carbonate-treated group had fewer manic episodes than the other groups. Treatment outcome, which was evaluated primarily in terms of the occurrence of major depression or manic episodes, was significantly related to characteristics of the index episode, ie, the episode that brought the patient into the study.", "The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/recurrence.\n Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score > or =20 entered the study and received open-label co-treatment with olanzapine and lithium for 6-12 weeks. Those meeting symptomatic remission criteria (Young Mania Rating Scale score < or =12; 21-item Hamilton depression scale score < or =8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5-20 mg/day (N=217), or lithium (target blood level: 0.6-1.2 meq/liter) (N=214).\n Symptomatic relapse/recurrence (score > or =15 on either the Young Mania Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapine-treated and 38.8% of lithium-treated patients. The noninferiority of olanzapine relative to lithium (primary objective) in preventing relapse/recurrence was met, since the lower limit of the 95% confidence interval on the 8.8% risk difference (-0.1% to 17.8%) exceeded the predefined noninferiority margin (-7.3%). Secondary results showed that compared with lithium, olanzapine had significantly lower risks of manic episode and mixed episode relapse/recurrence. Depression relapse/recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium-treated patients. Mean weight gain during open-label co-treatment was 2.7 kg; during double-blind monotherapy, weight gain was significantly greater with olanzapine (1.8 kg) than with lithium (-1.4 kg).\n These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium co-treatment. Both agents were comparable in preventing depression relapse/recurrence.", "Recently, the therapeutic benefit of lithium augmentation in old age has come into question. These data, in light of the documented high incidence of side effects after lithium use in elderly patients, resulted in the design of a prospective, placebo-controlled lithium augmentation withdrawal study in elderly patients with unipolar depression. Twelve eligible geriatric patients (10 women and 2 men; mean [+/-SD] age, 76.2 +/- 5.7 years) with DSM-III-R unipolar depression receiving adjunct lithium therapy were randomized to receive continued lithium augmentation or matching placebo (withdrawal rate 150 mg/day/wk). At each clinic visit, patients were assessed for depression (Montgomery-Asberg Depression Rating Scale and Geriatric Depression Rating Scale) and lithium-induced toxicities (a 21-item side-effect checklist, renal and thyroid biochemistry). Over the 2-year observation period, the placebo group reported a decrease in composite 21-item side-effect score and specific lithium toxicities (e.g., urinary urgency, hand tremor, and renal/thyroid abnormalities). Two patients in the lithium maintenance group had a recurrence of depression at 61 and 96 weeks, respectively, immediately after a stressful life event (cerebrovascular accident [CVA] or death of spouse), and two patients had a recurrence in the placebo group at 7 and 92 weeks, respectively, without any apparent changes in life stresses. No other prognostic risk factors for recurrence were identified. Depression that recurred in patients who were receiving placebo was relatively resistant to reinstitution of lithium augmentation therapy. In otherwise stable geriatric patients with unipolar depression, the documented benefits of reduced side effects should be weighed against the risk of recurrence and subsequent lithium resistance before withdrawal of lithium augmentation.", "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.", "Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder. Aims To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone.\n Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium (0.6-1.2 mmol/l) or valproate (50-125 microg/ml) received lithium or valproate plus either olanzapine 5-20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months.\n The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy 40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy 42 days; P=0.023).\n Patients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission, but not syndromic remission, for longer than those receiving lithium or valproate monotherapy.", "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.", "Prominent and persistent anxiety, depression, and/or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal side effects of typical neuroleptic medications often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and their treatment. For patients who remained distressed, controlled trials of supplemental thymoleptics were undertaken.\n In trial 1, 92 distressed (depressed and/or anxious) patients and 36 patients in a defect state (patients with negative symptoms) participated in a double-blind, intramuscular challenge that compared centrally acting benztropine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22 patients in a defect state were randomly assigned to a double-blind, neuroleptic medication dose-reduction group. In trial 3, 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were randomly assigned to a supplemental desipramine hydrochloride, lithium carbonate, or placebo group under double-blind conditions for 12 weeks.\n For patients who were already maintained on antiparkinsonian medication, impaired affect was not resolved by additional benztropine. Only distressed patients with a family history of severe mental disorder (often affective) showed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose, but negative symptoms persisted. Desipramine improved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improved in women only. Lithium positively affected multiple indexes of anxiety and anxious depression.\n Most often, persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits. Thymoleptics improve the nonphasic, chronic types of anxiety and depression in contrast to the acute, episodic forms, for which little support can be found in the literature.", "Long-term outcomes are often poor in patients with bipolar disorder despite treatment; more effective treatments are needed to reduce recurrences and morbidity. This study compared the efficacy of divalproex, lithium, and placebo as prophylactic therapy.\n A randomized, double-blind, parallel-group multicenter study of treatment outcomes was conducted over a 52-week maintenance period. Patients who met the recovery criteria within 3 months of the onset of an index manic episode (n = 372) were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2:1:1 ratio. Psychotropic medications were discontinued before randomization, except for open-label divalproex or lithium, which were gradually tapered over the first 2 weeks of maintenance treatment. The primary outcome measure was time to recurrence of any mood episode. Secondary measures were time to a manic episode, time to a depressive episode, average change from baseline in Schedule for Affective Disorders and Schizophrenia-Change Version subscale scores for depression and mania, and Global Assessment of Function scores.\n The divalproex group did not differ significantly from the placebo group in time to any mood episode. Divalproex was superior to placebo in terms of lower rates of discontinuation for either a recurrent mood episode or depressive episode. Divalproex was superior to lithium in longer duration of successful prophylaxis in the study and less deterioration in depressive symptoms and Global Assessment Scale scores.\n The treatments did not differ significantly on time to recurrence of any mood episode during maintenance therapy. Patients treated with divalproex had better outcomes than those treated with placebo or lithium on several secondary outcome measures." ]

[ "11099583", "17880315", "9875920", "492827", "10505365", "20233384", "17492326", "12946338", "17177928" ]

[ "Baby CareLink: using the internet and telemedicine to improve care for high-risk infants.", "Randomized controlled trial of vascular access in newborns in the neonatal intensive care unit.", "A randomized, controlled trial of computerized physiologic trend monitoring in an intensive care unit.", "Controlled clinical trial of pediatric telephone protocols.", "Telemedicine in the emergency department: a randomized controlled trial.", "Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions.", "A randomized trial of telemedicine-based collaborative care for depression.", "A randomised controlled trial of admission electronic fetal monitoring in normal labour.", "Adoption of a ventilator-associated pneumonia clinical practice guideline." ]

[ "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.", "To compare the effectiveness of two methods of vascular access in newborns.\n Randomized controlled trial.\n Neonatal intensive care unit in Regional Hospital of Valdivia, Chile.\n Seventy-four high-risk newborns.\n Peripherally inserted central catheter and peripheral intravenous catheter.\n Length of neonatal intensive care unit stay and incidence of sepsis and phlebitis. RESULTS/DATA ANALYSIS: There were no statistically significant differences in the length of the neonatal intensive care unit stay and in the incidence of sepsis between groups. There was a significant higher incidence of phlebitis in the peripheral intravenous catheter group.\n Although there was not a significant effect of the kind of catheter on length of neonatal intensive care unit stay, the peripherally inserted central catheter is recommended because of the decreased risk of phlebitis and the decreased number of venipuncture attempts and catheters needed to complete intravenous therapy.", "To assess whether the provision of computerized physiologic trend data could improve outcome in newborn infants requiring intensive care.\n Randomized, controlled trial, with subsidiary questionnaire studies.\n Tertiary neonatal intensive care unit with 12 intensive care cots.\n All infants admitted between January 1991 and September 1993 who were < or =32 wks gestation or >32 wks gestation, and ventilated for >4 hrs or asphyxiated.\n Randomization to one of four groups for first 7 days of life: A) no display of trend data; B) continuous display of trend data; C1) alternating 24-hr display of trend data, starting with display in first 24 hrs; and C2) alternating 24-hr display of trend data, starting with no display in first 24 hrs.\n The short-term effects of monitoring on patient outcome was judged by volume of colloid given, number of blood gases taken, and by measurement taken from cranial Doppler ultrasound. Medium-term measures included time ventilated, time given supplemental oxygen, death, time to death or discharge, and cranial ultrasound at discharge. Long-term outcome was assessed by neurodevelopmental status at age 1 to 4 yrs of age. Staff and parent questionnaires assessed their respective attitudes to the introduction of this technology. None of the patient outcome measures, short-, medium-, or long-term, demonstrated any significant benefit from the provision of computerized physiologic trend monitoring. Staff questionnaires demonstrated an acceptance of the system and an improved understanding of neonatal physiology as a result of computerized physiologic trends. Parent questionnaires demonstrated increased anxiety caused by the system in 11% of parents, although only 1% of parents continued to have concerns if the system were able to help their child.\n A randomized, controlled trial was unable to demonstrate any benefit to patients resulting from the introduction of a computerized physiologic trend monitoring system. Benefits of the system have been recognized, however, in subsidiary studies, staff education, and research studies.", "A randomized clinical trial of pediatric protocols administered by health assistants demonstrated an alternate method of handling telephone complaints in a large emergency room. The new system advised a higher medical examination rate than the current system in the emergency room probably bacause the current system has deficits with respect to collecting necessary information and making explicit decisions. This higher rate of recommended visits demonstrated in the emergency room was not confirmed in the two pediatric primary-care settings in which the protocol system was also tested. In addition to this use, the telephone protocols may also be useful in training medical and nursing students, in handling telephone complaints similar to a poison control center, in triaging problems in a rural or emergency medical service, and in providing a record of the telephone call.", "Emergency physicians and nurses were trained in telemedicine techniques in two emergency departments, one rural (low volume) and one suburban (high volume). Fifteen patient complaints were selected as appropriate for the study. Of 122 patients who met the inclusion criteria, 104 (85%) consented to participate. They were randomized to control and experimental groups. The suburban emergency physician diagnosed and treated the control patients. Experimental patients presenting to the high-volume emergency department were evaluated and treated by the telemedicine nurse in person and the rural emergency physician via the telemedicine link. Immediately before discharge all telemedicine patients were re-evaluated by the suburban emergency physician. Data collected on each patient included: diagnosis; treatment; 72 h return visits; need for additional care; and satisfaction of patient, physicians and nurses. There were no significant differences (P > 0.05) for occurrence of 72 h return visits, need for additional care or overall patient satisfaction. The average patient throughput time (from admission to discharge) was 106 min for the telemedicine group and 117 min for the control group. Telemedicine was a satisfactory technique for the chosen group of patients in the emergency department and was acceptable to the participants.", "Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs).\n Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria.\n Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: Two interventions prevent preterm births--smoking cessation and progesterone. Eight interventions prevent stillbirths--balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery. Eleven interventions improve survival of preterm newborns--prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome\n The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions.", "Evidence-based practices designed for large urban clinics are not necessarily portable into smaller isolated clinics. Implementing practice-based collaborative care for depression in smaller primary care clinics presents unique challenges because it is often not feasible to employ on-site psychiatrists.\n The purpose of the Telemedicine Enhanced Antidepressant Management (TEAM) study was to evaluate a telemedicine-based collaborative care model adapted for small clinics without on-site psychiatrists.\n Matched sites were randomized to the intervention or usual care.\n Small VA Community-based outpatient clinics with no on-site psychiatrists, but access to telepsychiatrists. In 2003-2004, 395 primary care patients with PHQ9 depression severity scores > or = 12 were enrolled, and followed for 12 months. Patients with serious mental illness and current substance dependence were excluded.\n Medication adherence, treatment response, remission, health status, health-related quality of life, and treatment satisfaction.\n The sample comprised mostly elderly, white, males with substantial physical and behavioral health comorbidity. At baseline, subjects had moderate depression severity (Hopkins Symptom Checklist, SCL-20 = 1.8), 3.7 prior depression episodes, and 67% had received prior depression treatment. Multivariate analyses indicated that intervention patients were more likely to be adherent at both 6 (odds ratio [OR] = 2.1, p = .04) and 12 months (OR = 2.7, p = .01). Intervention patients were more likely to respond by 6 months (OR = 2.0, p = .02), and remit by 12 months (OR = 2.4, p = .02). Intervention patients reported larger gains in mental health status and health-related quality of life, and reported higher satisfaction.\n Collaborative care can be successfully adapted for primary care clinics without on-site psychiatrists using telemedicine technologies.", "To test the hypothesis that the use of admission Electronic Fetal Monitoring (EFM) for healthy pregnant women in spontaneous labour would result in an increase in continuous EFM when compared to women who have had no admission EFM.\n A randomised controlled trial.\n The Midwives Birth Unit in Glasgow Royal Maternity Hospital, a major urban teaching hospital with approximately 5000 births per year.\n Healthy pregnant women admitted in normal labour, deemed low risk based on the midwives' birth unit admission criteria.\n Women were randomly allocated either to receive a routine 20-minute period of EFM at the time of admission (control group), or to receive no routine admission EFM (study group).\n Primary study outcomes, use of continuous EFM; and use of EFM additional to the admission test. Secondary outcomes: artificial rupture of membranes, use of fetal scalp electrode, fetal blood sample, syntocinon, epidural analgesia, number of vaginal examinations, rate of transfer to labour ward, and reason for transfer.\n There was no statistically significant difference between the groups for use of continuous monitoring, but significantly more women in the control group did receive additional EFM. There was no statistically significant difference between groups for any of the interventions studied.\n The use of admission EFM did not in itself lead to a cascade of intervention. Other factors including setting of care and philosophy of caregivers may have an effect on the rate of intervention in labour.", "The Academic Center for Evidence-based Practice (ACE) Star Model was used to implement an evidence-based clinical practice guideline (CPG) in order to decrease ventilator-associated pneumonia (VAP) incidence rates and ventilator days. The goal was to interrupt person-to-person transmission of bacteria and bacterial colonization using low-cost, evidence-based strategies to prevent VAP. DISCOVERY: Two geographically proximate medical centers, inclusive of five intensive care units located in the southwestern region of the United States had significant variations in their VAP rates.\n Using the U.S. Preventive Services Task Force grading criteria, the results of 69 studies were used to establish a clinical practice guideline to prevent ventilator-associated pneumonia. TRANSLATION: A clinical practice guideline was developed for the prevention of VAP and included five nursing activities: (a) head-of-bed elevation; (b) oral care; (c) ventilator tubing condensate removal; (d) hand hygiene; and (e) glove use. The effect of the CPG, inclusive of an educational intervention, was measured using an observational, prospective, quasi-experimental design. INTEGRATION: A multidisciplinary education team developed a self-learning packet, educational materials, and storyboards for the staff as dissemination strategies. Strategies also included e-mail, one-on-one teaching with clinicians, and feedback on guideline adoption and VAP rate reports.\n Observation data were collected to evaluate adoption of the CPG while caring for 106 ventilated patients. VAP rates changed at both hospitals although the change was not statistically significant. Additionally, the ICU length of stay declined at both facilities, causing cost savings.\n These results support the idea that adoption of evidence-based practices contributes to decreased VAP rates. For a successful program, ICU leaders should emphasize strategies that routinize adoption of evidence-based CPGs." ]

[ "16772251", "10190777", "11936063", "10416558", "9475639", "11371683", "2223891", "2375667", "8100607" ]

[ "Effects of a supervised home-based aerobic and progressive resistance training regimen in women infected with human immunodeficiency virus: a randomized trial.", "Moderate and high intensity exercise training in HIV-1 seropositive individuals: a randomized trial.", "Effectiveness of a home-based exercise intervention for HIV-infected adults: a randomized trial.", "Cardiopulmonary and CD4 cell changes in response to exercise training in early symptomatic HIV infection.", "The effect of exercise training on aerobic fitness, immune indices, and quality of life in HIV+ patients.", "Aerobic exercise: effects on parameters related to fatigue, dyspnea, weight and body composition in HIV-infected adults.", "Exercise intervention attenuates emotional distress and natural killer cell decrements following notification of positive serologic status for HIV-1.", "Progressive resistance exercise: effect on muscle function and anthropometry of a select AIDS population.", "Supervised exercise training improves cardiopulmonary fitness in HIV-infected persons." ]

[ "Women infected with human immunodeficiency virus (HIV) increasingly demonstrate abnormalities in fat distribution and metabolism; however, the effects of a home-based exercise regimen in this group have not been investigated.\n We conducted a 16-week randomized intervention study of a supervised home-based progressive resistance training and aerobic exercise program in 40 HIV-infected women with increased waist-hip ratio and self-reported fat redistribution. Cross-sectional muscle area and muscle attenuation were measured by computed tomography. Cardiorespiratory fitness was determined by calculated maximum oxygen consumption (VO2max) and strength by 1-repetition maximum.\n Cardiorespiratory fitness (VO2max) was markedly lower at baseline (median [95% confidence interval], 15.4 [8.3-25.2] mL x kg(-1) x min(-1)) than reported values for healthy female subjects (26-35 mL x kg(-1) x min(-1)). Subjects randomized to exercise had significant improvement in mean +/- SEM VO2max (1.5 +/- 0.8 vs -2.5 +/- 1.6 mL x kg(-1) x min(-1); P<.001) and endurance (1.0 +/- 0.3 vs -0.6 +/- 0.3 minute; P<.001). Strength increased at the knee extensors, pectoralis, knee flexors, shoulder abductors, ankle plantar flexors, and elbow flexors (all P<.001). Total muscle area (6 +/- 1 vs 2 +/- 1 cm2; P = .02) and attenuation (2 +/- 1 vs -1 +/- 1 Hounsfield unit; P = .03) increased in the exercise group. No significant difference was seen in lipid levels, blood pressure, or abdominal visceral fat between the groups, but subjects randomized to exercise reported improved energy and appearance.\n A 16-week, supervised, home-based exercise regimen improved measures of physical fitness in HIV-infected women. The effects on strength were most significant, but improvements in cardiorespiratory fitness, endurance, and body composition were also seen.", "HIV-infected individuals are frequently active, but guidelines for exercise in this population lack scientific support, since studies on the effects of exercise training on immunologic variables of HIV-1 positive individuals have shown conflicting results. Exercise capacity, immunologic markers (CD4, CD8 and CD4:CD8 ratio), anthropometric measurements, and depression scores were evaluated to compare the effects of two intensities of aerobic exercise on HIV-1 seropositive individuals. Twenty-one healthy subjects (14 men, 7 women), carriers of the HIV-1 virus (CD4>200 cells x mm(-3)), and inactive for at least 6 months, completed a 12 week exercise training program (36 sessions of 1 h, 3 times per week), in a moderate intensity group (60+/-4% of maximal heart rate) or a high intensity group (84+/-4% of maximal heart rate). Exercise capacity estimated by treadmill time was increased significantly in both moderate intensity (680+/-81 s before; 750+/-151 s after) and high intensity (651+/-122 s before; 841+/-158 s after) groups, but the high intensity group presented a significantly larger increment (p<0.01). There were no significant changes in the immunologic variables, anthropometric measurements or depression scores. Thus, HIV-seropositive individuals that participate in moderate and high intensity exercise programs are able to increase their functional capacity without any detectable changes in immunologic variables, anthropometric measurements or depression scores.", "The authors conducted a randomized controlled trial to assess the impact of a 15-week (20 minutes three times per week) home-based aerobic exercise intervention versus usual care on the physical endurance, immune status, and self-reported health status of 99 HIV-infected adults. In the exercise group, there was no improvement in physical endurance or health-related quality of life (HRQOL), except in the Medical Outcomes Study-HIV Health Survey Overall Health subscale (difference = 12.1, 95% confidence interval = 2.0-22.2, p = .02). Although physical endurance levels were maintained at baseline levels in the intervention group and declined in the control group, differences between the groups were small and not significant. There were also no significant changes in CD4+ T-lymphocyte counts. Exercise appears to be safe in HIV-infected patients. Improvements in physical endurance and HRQOL might result if the exercise protocol is longer or progressive. Further research is needed to establish guidelines for exercise in patients on highly active antiretroviral therapy.", "The purposes of the present study were to assess the effects of a 12-wk laboratory based aerobic exercise program on cardiopulmonary function, CD4 cell count, and physician-assessed health status among symptomatic pre-AIDS HIV-infected individuals (N = 28) and to assess the degree to which ill health was associated with exercise relapse.\n Responses to graded exercise test, physician-assessed health status, and CD4 cell counts were determined at baseline and 12-wk follow-up for participants randomly assigned to exercise or control conditions, and reasons for exercise noncompliance were recorded.\n Approximately 61% of exercise-assigned participants complied (> 50% attendance) with the exercise program, and analyses of exercise relapse data indicated that obesity and smoking status, but not exercise-associated illness, differentiated compliant from noncompliant exercisers. Compliant exercisers significantly improved peak oxygen consumption (VO2peak; 12%), oxygen pulse (O2pulse; 13%), tidal volume (TV; 8%), ventilation (VE; 17%), and leg power (25%) to a greater degree than control participants and noncompliant exercisers (all P < 0.05). Although no group differences in health status were found, a significant interaction effect indicated that noncompliant exercisers' CD4 cells declined (18%) significantly, whereas compliant exercisers' cell counts significantly increased (13%; P < 0.05).\n We conclude that although aerobic exercise can improve cardiopulmonary functioning in symptomatic HIV-infected individuals with minimal health risks, attention to factors associated with exercise adherence is warranted.", "Thirty four HIV+ patients participated in a 6-wk aerobic exercise training program to determine whether exercise improved aerobic fitness, immune indices, and quality of life.\n Subjects were assigned to three groups: control (no regular aerobic exercise), moderate exercise, and heavy exercise training. At study entry and exit (in each subject) we evaluated aerobic function with a symptom limited cardiopulmonary exercise test, immune indices with CD4 counts and Candida skin tests, viral replication with plasma HIV RNA measurements, and quality of life with a HIV+ population validated questionnaire.\n Aerobic fitness increased significantly in both exercise groups relative to the control group; immune indices changed very little among all three groups; however, the Candida skin tests (mm2) increased significantly in the moderate group; viral replication was essentially unchanged in all three groups; quality of life (QOL) markers improved in both exercising groups but not the control group. There were no opportunistic infections during the study.\n Exercise training resulted in a substantial improvement in aerobic function while immune indices were essentially unchanged. Quality of life markers improved significantly with exercise. Exercise training is safe and effective in this patient group and should be promoted for HIV+ patients.", "The purpose of the study was to examine the effects of aerobic exercise on physiological fatigue (time on treadmill), dyspnea [rate of perceived exertion (RPE) and forced expiratory volume at 1 s (FEV1)], weight, and body composition in HIV-1-infected adults (200-499 x 106 CD4+ cells/l).\n The study was a randomized, wait-listed, controlled clinical trial of aerobic exercise in HIV-1-infected adults on signs and symptoms associated with HIV-1 infection or its treatment.\n Sixty subjects were recruited and randomized to two groups. Experimental subjects completed a 12-week supervised exercise program. Control subjects continued usual activity from baseline to week 12 and were then were enrolled in the exercise program.\n At baseline, the groups were similar in age, weight, body mass index [mean body mass index (BMI) > 27], time since diagnosis, number of symptoms, CD4+ cell count, and number on protease inhibitor therapy (n = 7). Despite disproportionate attrition from the exercise group (38%), exercise subjects were able to remain on the treadmill longer, lost weight, decreased BMI, subcutaneous fat, and abdominal girth when compared to controls. The improvement in weight and body composition occurred without a decrease in kilocalories consumed. Exercise did not seem to have an effect on RPE, a surrogate for dyspnea, and FEV1. There was no significant difference in either the change in CD4+ cell count, percentage or copies of plasma HIV-1 RNA between groups.\n We conclude that supervised aerobic exercise training safely decreases fatigue, weight, BMI, subcutaneous fat and abdominal girth (central fat) in HIV-1-infected individuals. It did not appear to have an effect on dyspnea.", "The impact of aerobic exercise training as a buffer of the affective distress and immune decrements which accompany the notification of HIV-1 antibody status in an AIDS risk group was studied. Fifty asymptomatic gay males with a pretraining fitness level of average or below (determined by predicted VO2 max) were randomly assigned to either an aerobic exercise training program or a no-contact control condition. After five weeks of training, at a point 72 hours before serostatus notification, psychometric, fitness and immunologic data were collected on all subjects. Psychometric and immunologic measures were again collected one-week postnotification. Seropositive controls showed significant increases in anxiety and depression, as well as decrements in natural killer cell number following notification whereas, seropositive exercisers showed no similar changes and in fact, resembled both seronegative groups. These findings suggest that concurrent changes in some affective and immunologic measures in response to an acute stressor might be attenuated by an experimentally manipulated aerobic exercise training intervention.", "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.", "We attempted to measure cardiopulmonary effects, CD4 counts, and perceived sense of well-being in 25 individuals moderately to severely immunocompromised from HIV infection (mean entry CD4 count = 144.microliters-1) before and after a 24-wk program of exercise training. Only six subjects completed the 24-wk program. All six showed evidence of a training effect. Statistically significant improvements were seen in maximal oxygen consumption (VO2max), oxygen pulse, and minute ventilation. Submaximal exercise performance improved significantly by 12 wk in the 10 individuals available for testing: decreases were seen in heart rate, rate pressure product, and rate of perceived exertion. White blood cell counts and T-lymphocyte subsets were stable at 12 and 24 wk in the subjects available for testing. High depression/anxiety scores on a mental health inventory (General Health Questionnaire) correlated with low CD4 counts. Scores did not correlate with compliance with the exercise program. There was a trend (P < 0.10) for scores to improve over time among those individuals who attended > or = 80% of scheduled exercise sessions. We conclude that exercise training is feasible and beneficial for some HIV-infected individuals." ]

[ "19996196", "19570573", "14711911", "15665326", "10528036", "1859050", "2863676", "18399862", "7589382" ]

[ "Pirfenidone in idiopathic pulmonary fibrosis.", "Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial.", "A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis.", "Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis.", "A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis.", "Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial.", "Alternate-day prednisone reduces morbidity and improves pulmonary function in cystic fibrosis.", "Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis.", "Recombinant human DNase I in cystic fibrosis patients with severe pulmonary disease: a short-term, double-blind study followed by six months open-label treatment." ]

[ "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.", "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.", "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 (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.", "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.", "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)", "A randomised, double-blind, placebo-controlled study examined the effects of alternate-day prednisone therapy on morbidity and progression of lung disease in cystic fibrosis (CF). At baseline the patients (aged 1-12 years) had mild to moderate lung disease, and the prednisone group did not differ significantly from the placebo group for any values measured. After 4 years, the prednisone-treated group had significant advantages over the placebo group for height, weight, vital capacity, forced expiratory volume in 1 s, peak flow rate, erythrocyte sedimentation rate, and serum IgG. The prednisone-treated group required 9 admissions to hospital for CF-related pulmonary disease compared with 35 for the placebo group. There were no steroid-induced side-effects. To rule out bias in case selection, 69 CF clinic patients comparable in age and clinical status but not included in the study were compared with the placebo group at 4 years; no significant differences between the groups were found.", "Although pulmonary rehabilitation is effective for patients with COPD, its efficacy in patients with IPF is unknown. The purpose of this study was to evaluate the effects of pulmonary rehabilitation in IPF.\n Thirty patients diagnosed with IPF, according to the consensus statement, were randomly assigned to the rehabilitation group or the control group. The pulmonary rehabilitation mainly consisted of a 10-week programme of exercise training. Pulmonary function, blood gas analysis, 6MWD, dyspnoea rating with the baseline dyspnoea index and health-related quality of life score on the St George's Respiratory Questionnaire were evaluated at baseline and after the programme.\n Assessment of efficacy was carried out on 13 patients who completed the programme and 15 patients in the control group. There were no significant effects of the programme on measures of pulmonary function, values of arterial blood gas analysis or dyspnoea rating. Although there were some differences in the baseline 6MWD and total health-related quality of life score which were not statistically significant, marked improvements were observed in the 6MWD (mean difference 46.3 m (95% CI: 8.3-84.4), P < 0.05) and the total health-related quality of life score (-6.1 (95% CI: -11.7 to -0.5), P < 0.05).\n Pulmonary rehabilitation improves both exercise capacity and health-related quality of life in patients with IPF.", "Chronic pulmonary infection is the major cause of morbidity and mortality in cystic fibrosis (CF). Recombinant human deoxyribonuclease (rhDNase) in vitro has been shown to dramatically reduce the viscoelasticity of the sputum from CF patients. Phase II and III clinical trials have shown the drug to be safe, and that patients with a forced vital capacity (FVC) of > 40% predicted show an improvement in pulmonary function when receiving rhDNase. The current study evaluates the safety and efficacy of rhDNase in the most severly ill CF patients (FVC < 40% predicted). A double-blind, randomized, placebo-controlled trial in which patients received either 2.5 mg rhDNase twice daily or placebo for a period of 14 days followed by a 6 month open extension period (OEP) is reported. Seventy patients were recruited for the double-blind study, and 64 entered the OEP of whom 38 completed. During the OEP, all patients received 2.5 mg rhDNase twice daily. In both the double-blind period and the OEP the drug appeared to be safe. During the double-blind study, forced expiratory volume in one second (FEV1) and FVC improved in both groups but there was no statistically significant difference between the groups. In the OEP, there was mean improvement in percentage predicted FEV1 and FVC, 9 and 18%, respectively, for all patients participating. In conclusion, DNase is safe when administered in conjunction with a rigorous regimen of chest physiotherapy to severely ill patients (FVC < 40% predicted) with CF. The double-blind, 14 day study showed no significant improvement in pulmonary function but some patients may have improved after longer administration of rhDNase." ]

[ "14707396", "8328732", "1742504", "8607484", "2904006", "7920500", "8091141", "1905501", "11802750" ]

[ "Efficacy and tolerability of pantoprazole compared with misoprostol for the prevention of NSAID-related gastrointestinal lesions and symptoms in rheumatic patients.", "Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group.", "Misoprostol prevents NSAID-induced gastroduodenal lesions in patients with osteoarthritis and rheumatoid arthritis.", "Misoprostol and ranitidine in the prevention of NSAID-induced ulcers: a prospective, double-blind, multicenter study.", "Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial.", "[Misoprostol in the prevention of gastric erosions caused by nonsteroidal anti-inflammatory agents].", "Efficacy of 12 months' misoprostol as prophylaxis against NSAID-induced gastric ulcers. A placebo-controlled trial.", "Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized, controlled trial.", "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." ]

[ "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 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.", "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.", "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.", "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.", "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.", "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.", "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).", "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." ]

[ "7683942", "9093725", "10213009", "7542021", "21444866", "9350242", "9849452", "16822992", "11783226" ]

[ "Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.", "Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer.", "A phase III study of irinotecan (CPT-11) versus best supportive care in patients with metastatic colorectal cancer who have failed 5-fluorouracil therapy. V301 Study Group.", "Cost-effectiveness of palliative chemotherapy in advanced gastrointestinal cancer.", "Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial.", "[Prospective controlled study on the usefulness of Carmofur as a postoperative adjuvant chemotherapy for colorectal cancer].", "Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group.", "Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.", "[Clinical study on treatment of mid-late stage gastric carcinoma by composite xiansu capsule combined with chemotherapy]." ]

[ "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.", "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.", "In a prospective multicenter trial, 279 patients with metastatic colorectal cancer who had failed 5-fluorouracil therapy were randomized 2:1 to receive either best supportive care (BSC) plus treatment with the topoisomerase I inhibitor, irinotecan (CPT-11; Rhône-Poulenc Rorer, Antony, France), at a dose of 350 mg/m2 every 3 weeks or BSC alone. Overall survival, the primary end point of the study, was significantly improved in patients receiving the irinotecan treatment. Only 14% of patients receiving BSC alone were alive at 1 year compared with 36% in the irinotecan group. After adjustment for prognostic factors such as performance status, the difference in survival favoring irinotecan remained highly significant (P = .001). The benefit of irinotecan was also observed through significantly longer survival without performance status deterioration, longer survival without more than 5% weight loss, and longer duration of pain-free survival. Appreciable deterioration in global quality of life (50% reduction from baseline) occurred significantly later in the irinotecan-treated patients than in the controls. Additionally, quality of life analyses of all symptoms, except diarrhea, mean scores were significantly in favor of patients assigned to irinotecan treatment than those assigned to BSC. This is the first time that the benefit of second-line chemotherapy has been demonstrated by a randomized controlled trial in advanced colorectal cancer.", "Chemotherapy may relieve tumor-related symptoms, may improve quality of life and prolong survival in advanced gastrointestinal cancer. The extent of such improvements is unclear despite the extensive use of this treatment modality, and there are no studies concerning the economic cost of any gain achieved in the quantity and quality of life by chemotherapy.\n Between January 1991 and May 1992, 61 patients with inoperable cancer (18 gastric, 22 pancreatic or biliary, and 21 colorectal) were randomized to either primary 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 achieve palliation. All economic costs for medical care were prospectively recorded, and marginal cost-effectiveness analyses were performed.\n More patients in the primary chemotherapy group (19/33, 58%) had improved/prolonged high quality of life (QoL-patient, minimum duration 4 months) than in the best supportive care group (8/28, 29%, p < 0.05). Overall survival and quality-adjusted survival were significantly longer in the primary chemotherapy group (median 9 vs. 4 months, p < 0.05), and median 7 vs. 2 months, p < 0.05, respectively). When analysed by cancer site, survival was significantly prolonged in gastric cancer patients (median 10 vs. 4 months, p < 0.02), but not in colorectal (median 12 vs. 6 months, p = 0.1) and pancreatic-biliary cancer patients (median 8 vs. 5 months, p = 0.8). The average cost for all medical care was approximately 50% higher in the primary chemotherapy group, but the average cost per day was the same in the two groups. Hospitalization accounted for most of the costs in both groups. The incremental costs per gained year of life was SEK 166,400 ($21,300), per gained quality-adjusted year of life SEK 157,200 ($20,200), and per QoL-patient SEK 160,300 ($20,600). These costs were lower for gastric and colorectal cancer patients, and much higher for pancreatic-biliary cancer patients.\n The results of this study suggest that palliative chemotherapy is cost-effective in patients with advanced gastric and colorectal cancer. Knowledge about survival and quality of life benefits is still limited in patients suffering from gastric and pancreatic-biliary cancer.", "After curative resection, the prognosis of gastroesophageal adenocarcinoma is poor. This phase III trial was designed to evaluate the benefit in overall survival (OS) of perioperative fluorouracil plus cisplatin in resectable gastroesophageal adenocarcinoma.\n Overall, 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction (GEJ), or stomach were randomly assigned to either perioperative chemotherapy and surgery (CS group; n = 113) or surgery alone (S group; n = 111). Chemotherapy consisted of two or three preoperative cycles of intravenous cisplatin (100 mg/m(2)) on day 1, and a continuous intravenous infusion of fluorouracil (800 mg/m(2)/d) for 5 consecutive days (days 1 to 5) every 28 days and three or four postoperative cycles of the same regimen. The primary end point was OS.\n Compared with the S group, the CS group had a better OS (5-year rate 38% v 24%; hazard ratio [HR] for death: 0.69; 95% CI, 0.50 to 0.95; P = .02); and a better disease-free survival (5-year rate: 34% v 19%; HR, 0.65; 95% CI, 0.48 to 0.89; P = .003). In the multivariable analysis, the favorable prognostic factors for survival were perioperative chemotherapy (P = .01) and stomach tumor localization (P < .01). Perioperative chemotherapy significantly improved the curative resection rate (84% v 73%; P = .04). Grade 3 to 4 toxicity occurred in 38% of CS patients (mainly neutropenia) but postoperative morbidity was similar in the two groups.\n In patients with resectable adenocarcinoma of the lower esophagus, GEJ, or stomach, perioperative chemotherapy using fluorouracil plus cisplatin significantly increased the curative resection rate, disease-free survival, and OS.", "A prospective controlled study, the 7th cooperative study of the Japanese Foundation for Multidisciplinary Treatment, was conducted to evaluate the usefulness of concomitant therapy with MMC + HCFU as a postoperative adjuvant therapy in patients with colorectal cancer who had undergone curative resection for a period of 2 years and 11 months from February, 1986. The Dukes B and C patients with colorectal cancer classified by macroscopic examination who had an intravenous MMC 6 mg/m2 on the day of operation and followed by oral HCFU for 12 months from 2 weeks after operation (Group X) were compared with patients who had operation only (Group Y). Some 978 patients with colon cancer and 713 patients with rectal cancer were enrolled in the study, 85 (5.0%) of whom were not eligible. The 5-year survival rate of Group X in colon cancer was 79.3% and that of Group Y was 76.4%: thus the survival rate of Group X was slightly better than that of Group Y, but no significant difference was found between the two groups. Subset analysis revealed that the survival rate of Group X in advanced cancer of stage III b + IV, according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus in Japan, was 62.4% and that of Group Y was 46.2%. Thus, the survival rate of Group X was significantly better than that of Group Y (logrank test: p = 0.035, generalized Wilcoxon test: p = 0.025). The disease-free survival rate was not significantly different between the groups with colon cancer and rectal cancer. The above results suggest that HCFU is useful for patients with a high risk of recurrence who had advanced colon cancer (stage III b + IV). However, additional prospective studies are required to verify them.", "The aim of the present trial was to evaluate the effects of chemotherapy on the quality of life and survival of patients with advanced non-small cell lung cancer (NSCLC) (stage IIIB or IV). In a controlled multicentre trial, patients were randomised to receive supportive care only or supportive care plus chemotherapy. Chemotherapy consisted of intravenous (i.v.) carboplatin 300 mg/m2 on day 1 and etoposide 120 mg/m2 orally on days 1-5 every 4 weeks for a maximum of eight courses. Quality of life was measured at randomisation and prior to each treatment course and at corresponding 4-week intervals in the control arm, using the EORTC QLQ-C30 + LC13 questionnaire. 48 patients were randomised (supportive care 26, chemotherapy 22), being eligible for comparative analyses. Another 102 patients, 97 of which received chemotherapy, were subsequently included in the study on an individual treatment preference basis. Data from these patients were used for confirmative purposes. Patients in the chemotherapy group reported better overall physical functioning and symptom control compared with the supportive care group. Group differences were smaller within the psychosocial domain, although trends were seen in favour of the chemotherapy group. No significant differences were seen in favour of the supportive care group, except for hair loss. Median survival times were 29 weeks in the chemotherapy group versus 11 weeks in the supportive care group, and 1-year survival rates were 28% versus 8%. Quality of life and survival outcomes were similar in the randomised and non-randomised patients receiving chemotherapy. No treatment-related deaths occurred. In conclusion, treatment with carboplatin and etoposide can improve both the quality of life and the survival of patients with advanced NSCLC.", "A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer.\n We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival.\n ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P=0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001).\n In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival. (Current Controlled Trials number, ISRCTN93793971 [controlled-trials.com].).\n Copyright 2006 Massachusetts Medical Society.", "To assess the effect and mechanism of composite Xiansu Capsule (CXSC) combined with chemotherapy in treating gastric carcinoma of mid-late stage.\n The 61 patients of the test group were treated by CXSC combined with chemotherapy and 30 patients of the control group treated with chemotherapy alone. The effect of treatment and cell mediated immunity of patients were observed.\n The effective rate of the test group and the control group was 32.8% and 13.3% respectively (P < 0.05), the chemotherapy caused toxic reaction occurrence was less in the former than that in the latter group (P < 0.01). The CD3 level of patients in the test group was decreased, and CD4/CD8 level was raised obviously, which suggested that CXSC had immuno-regulating effect on T-cells.\n CXSC could enhance the efficacy and reduce the toxic side-effect of chemotherapy. To regulate the cell mediated immunity of patients is possibly its mechanism." ]

[ "17710485", "3943336", "2233916", "8625660", "9713447", "8636828", "1521875", "3514164", "2190515" ]

[ "Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization.", "Role of corticosteroids in the development of pneumonia in mechanically ventilated head-trauma victims.", "Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial.", "Effects of long-term treatment with corticosteroids in COPD.", "Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease.", "Pilot study to assess the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis.", "Role of corticosteroids in the management of chronic obstructive lung disease: factors predicting response.", "Corticosteroids in COPD. A clinical trial and reassessment of the literature.", "Corticosteroids prevent early deterioration in patients with moderately severe Pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome (AIDS)" ]

[ "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.", "The development of pneumonia was monitored in head-trauma patients requiring mechanical ventilation. Of the 66 patients studied, 15 (23%) developed pneumonia within 14 days after ICU admission. In each case the diagnosis was based on x-ray evidence and at least two of the following: increased white blood cell count, increased fever, and/or increased sputum production with a predominant organism on the sputum stain. Coagulase-positive Staphylococcus aureus was the most common etiologic agent. There was no difference in the occurrence of pneumonia between patients treated with no steroids or with low, moderate, or high steroid doses. Although there was an association between thiopental use and the development of pneumonia, dexamethasone treatment was not a significant risk factor in the development of pneumonia in this patient population.", "Preliminary reports suggest that patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia may benefit from the addition of corticosteroid treatment to antibiotic therapy.\n We conducted a double-blind, placebo-controlled trial to assess the efficacy of adjunctive corticosteroids in patients with AIDS and severe P. carinii pneumonia. Patients with marked abnormalities in gas exchange who had been treated with antibiotics for less than 72 hours were randomly assigned to receive either methylprednisolone (40 mg) or placebo every 6 hours for 7 days, in addition to treatment for 21 days with trimethoprim-sulfamethoxazole. The primary outcome measures were survival until hospital discharge and the development of respiratory failure.\n Twenty-three patients were enrolled in the study; there were no significant differences in base-line clinical or laboratory measures between the two treatment groups. Of 12 patients treated with corticosteroids, 9 (75 percent) survived until hospital discharge, as compared with only 2 of 11 placebo recipients (18 percent) (P less than 0.008). Respiratory failure developed in nine placebo recipients, as compared with only three patients treated with corticosteroids (P less than 0.008). No patient required the interruption or discontinuation of corticosteroid or antibiotic treatment because of toxicity or a complicating event. Because of the marked difference in survival, it was deemed unethical to continue the trial, and the study was terminated.\n Early adjunctive corticosteroid therapy can improve survival and decrease the occurrence of respiratory failure in patients with AIDS and severe P. carinii pneumonia.", "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.", "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.", "To determine the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis.\n We report a pilot study of 49 patients with cystic fibrosis and moderate to severe bronchial obstruction (forced expiratory volume in 1 second < or = 55% of the predicted value); 25 patients were given inhaled corticosteroids for 30 days (1500 micrograms of beclomethasone via spacer), and 24 patients had the same standard treatment but no inhaled corticosteroids.\n Forced vital capacity, forced expiratory volume in 1 second, and airway resistance showed significant improvement in both study groups, but thoracic gas volume and the diffusion capacity of the lung for carbon monoxide improved significantly only in the group given inhaled corticosteroids. When concomitant medications were taken into account, analysis of variance confirmed a significant effect of inhaled corticosteroids on the improvement of thoracic gas volume.\n Inhaled corticosteroids in combination with standard treatment can contribute to the improvement of lung function in patients with cystic fibrosis and moderate to severe bronchial obstruction. Our preliminary data seem encouraging enough to warrant a multicenter, long-term, blind control study.", "A double-blind crossover trial of prednisolone was conducted in 70 patients of chronic obstructive lung disease (COLD). Emphysema dominated the clinical picture in 38, rest being chronic bronchitis with varying degrees of air trapping. None of the patients had clinical asthma. All the patients had obtained maximal benefit from an optimal dose of bronchodilators prior to entering the study. Prednisolone in a dose of 0.8 mg/kg was prescribed in a double blind crossover manner with identical appearing placebo tablets. Patients were evaluated on a weekly basis for an objective as well as a subjective response and side effects of therapy. Thirty-four patients demonstrated a statistically significant improvement in pulmonary functions. In 20 others only subjective response was observed. A good objective response was predicted by a pre-study variability in FEV1, disease duration of less than 10 years and a history of smoking less than 50 pack years.", "A placebo-controlled, double-blind cross-over trial was conducted to assess whether 16 men with chronic obstructive pulmonary disease (COPD) would benefit from orally taken corticosteroids. Two weeks of treatment with 40 mg of prednisone daily did not result in improvement of pulmonary symptoms or function in the group as a whole, although one patient had small improvement in airflow. The baseline spirometric data and beta-agonist responsiveness of the patients in the study were then compared to a reference population consisting of 264 men who fulfilled a criteria for chronic obstruction out of 730 men who comprised a systematic sample drawn from all patients referred for spirometry at three hospitals. Our study subjects and those of five similar trials of corticosteroids in COPD had more severe obstruction than this reference group. Furthermore, the proportion of steroid responders found in each study was inversely related to the baseline FEV1 of the patients examined. It appears that previous studies of corticosteroids in COPD may have overestimated the number of COPD patients who might benefit from corticosteroids, due to a bias resulting from the selection of severely obstructed subjects.", "To determine whether oral corticosteroids can prevent early deterioration in patients with acquired immunodeficiency syndrome (AIDS)-related Pneumocystis carinii pneumonia.\n Prospective, double-blind, placebo-controlled, randomized trial.\n Included patients were having their first P. carinii pneumonia episode, had no other known active pulmonary pathology, had no contraindications for corticosteroids, received no anti-P. carinii pneumonia medications for more than 48 hours, and had oxygen saturation by pulse oximetry of 85% or more and less than 90% at rest or a 5-percentage-point decrease in oxygen saturation with exercise while breathing room air. Consenting subjects were randomly assigned to prednisone, 60 mg/d for 7 days, followed by a progressive tapering over 14 days or to an identical placebo. Early deterioration, the endpoint of the trial, was defined as a 10% decrease in baseline oxygen saturation on day 3 or thereafter. The cases of patients developing early deterioration were considered to be failures of treatment; the code was then broken, and the patient's treatment was left to the judgment of the treating physician. Sequential analysis was done with the primary variable being development of early deterioration.\n The trial was terminated 5 April 1989 on the basis of the sequential analysis when a total of nine episodes of early deterioration had occurred in the first 37 patients at an overall significance level of P = 0.0136. A total of 8 of 19 placebo-treated patients (42.1%) developed early deterioration compared with only 1 of 18 patients (5.6%) treated with corticosteroids. Baseline characteristics were not statistically different between the two treatment groups. The adjusted odds ratio for the treatment effect was 5.87 (95% CI, 1.27 to 27.4). The adjusted point estimates for the probability of early deterioration in the placebo and corticosteroid groups were 43% and 12%, respectively. All 8 patients in the placebo group developing early deterioration recovered rapidly with addition of corticosteroid treatment. The single patient with early deterioration in the corticosteroid group died on day 6 from overwhelming P. carinii pneumonia, as documented at autopsy. The corticosteroid group had an increased exercise tolerance on day 7 that persisted at day 30.\n Oral corticosteroids prevent early deterioration and increase exercise tolerance in patients with moderately severe AIDS-related P. carinii pneumonia." ]

[ "16489694", "8885732", "8688399", "10521736", "6988006", "6990761", "9259905", "1879595", "17272618" ]

[ "Ritodrine in oral maintenance of tocolysis after active preterm labor: randomized controlled trial.", "The clinical efficacy of oral tocolytic therapy.", "Double-blind evaluation of ritodrine sustained release for oral maintenance of tocolysis after active preterm labour.", "Maintenance oral nifedipine for preterm labor: a randomized clinical trial.", "The influence of betamethasone and orciprenaline on the incidence of respiratory distress syndrome in the newborn after preterm labour.", "Oral ritodrine maintenance in the treatment of preterm labor.", "A placebo-controlled randomized trial of the terbutaline pump for prevention of preterm delivery.", "The use of micronized progesterone in the treatment of menace of preterm delivery.", "Randomized trial of a single repeat dose of prenatal betamethasone treatment in imminent preterm birth." ]

[ "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.", "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.", "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.", "This study was undertaken to evaluate the efficacy of maintenance oral nifedipine in patients initially treated with intravenous magnesium sulfate for preterm labor.\n Patients with a diagnosis of preterm labor between 24 and 33.9 weeks' gestation were randomly assigned to receive either maintenance tocolytic therapy with oral nifedipine (20 mg every 4-6 hours) or no treatment (control) after discontinuation of magnesium tocolysis. Pregnancy and neonatal outcomes were evaluated. A sample size of 50 patients was required to detect a 10-day difference in mean time gained (beta =.2, alpha =.05). Statistical analyses were based on intent to treat. The t, chi(2), and Fisher exact tests were performed.\n Seventy-four patients were randomly assigned to receive either oral nifedipine (n = 37) or no treatment (n = 37). There were no statistically significant differences in age, race, parity, preterm delivery risk factors, enrollment gestational age, results of cervical examination, delivery gestational age, time gained, or neonatal complications between the groups. Delivery gestational age (mean +/- SD) was 35.4 +/- 3.2 weeks for patients randomly assigned to receive nifedipine and 35.3 +/- 3.2 weeks for patients who received no treatment (P =.9). Time gained during pregnancy was 37 +/- 23.9 days in the nifedipine group and 32.8 +/- 20.4 days in the control group (P =.4).\n Maintenance therapy with oral nifedipine does not significantly prolong pregnancy in patients initially treated with intravenous magnesium sulfate for preterm labor.", "In a randomized double-blind trial on antenatal corticosteroid treatment for the prevention of respiratory distress syndrome (RDS) a corticosteroid related beneficial effect was found. Possibly of more significance was the finding that the children born within 12 hours of their mother's admission to hospital showed a higher incidence of RDS than those born between 12 hours and one week after admission even in the placebo and untreated groups. Bèta-adrenergic drugs seemed to exert no other influence on the occurrence of RDS than can be explained by the delay of delivery. Prolonged ruptured membranes appeared to decrease the incidence of RDS to the same extent as other symptoms of threatened preterm labour.", "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.", "To determine the efficacy of the terbutaline pump for the prevention of preterm delivery, patients in preterm labor defined by progressive cervical change underwent intravenous magnesium sulfate tocolysis (with or without oral indomethacin, as necessary), and once labor was arrested, were randomized to one of three treatment arms: terbutaline by pump, saline by pump (blinded), or oral terbutaline. If recurrent preterm labor occurred despite maximization of therapy, the treatment arm was determined and therapy was changed; saline pump and oral terbutaline were switched to terbutaline pump, terbutaline pump was switched to oral terbutaline. Patients who continued to labor were readmitted for aggressive intravenous therapy. Women randomized to the terbutaline pump (n = 15), saline pump (n = 12), and oral terbutaline (n = 15) groups were similar in terms of gravidity, parity, days of tocolysis before study entry, gestational age at entry, and cervical dilatation at entry. The mean gestational age at delivery was the same in all three groups (35 weeks), as were neonatal outcomes. Terbutaline by pump, saline by pump, and oral terbutaline appear equivalent for the prevention of preterm delivery. The terbutaline pump should remain experimental.", "The results of a study concerning the treatment of acute menace of preterm labor are given: beta-mimetics were administered intravenously in all cases (44) and micronized progesterone or placebo was administered orally after classical double-blind randomization (22 cases in each group). The mean index of pregnancy prolongation was the same in both groups. However the mean duration of the intravenous perfusion and the mean quantity of beta-mimetics administered intravenously were significantly reduced in the progesterone group (P less than 0.01). The mean duration of hospital stay was also significantly reduced (P less than 0.05). Cost and risks are finally significantly lessened.", "A single dose of prenatal betamethasone treatment decreases neonatal morbidity rates when administered within 7 days before preterm delivery. A single repeat dose or booster dose of betamethasone before delivery has been proposed to be effective, but its efficacy has not been subjected to a randomized, blinded trial.\n Women with imminent delivery before 34.0 gestational weeks were eligible if they remained without delivery for >7 days after a single course of betamethasone. After stratification, a single repeat dose of betamethasone (12 mg) or placebo was administered. The primary outcome was survival without respiratory distress syndrome or severe intraventricular hemorrhage (grade 3 or 4).\n A total of 249 mothers had been enrolled by the time the study was discontinued. All of the 159 infants in the betamethasone group and 167 in the placebo group were born before 36 weeks of gestation. The intact survival rate was unaffected and was lower than anticipated, because the gestational age-adjusted incidence of respiratory distress syndrome was higher than the population incidence. The requirement for surfactant therapy in respiratory distress syndrome was increased in the betamethasone group. According to posthoc analysis of the data for 206 infants who were delivered within 1 to 24 hours, the betamethasone booster tended to increase the risk of respiratory distress syndrome and to decrease intact survival rates.\n According to this study, a single booster dose of betamethasone just before preterm birth may perturb respiratory adaptation. These results caution against uncontrolled use of a repeat dose of glucocorticoid in high-risk pregnancies." ]

[ "9676667", "14996698", "12038932", "8942777", "9708752", "9872878", "10789326", "12701945", "9676668" ]

[ "Effect on the quality of peer review of blinding reviewers and asking them to sign their reports: a randomized controlled trial.", "Effects of training on quality of peer review: randomised controlled trial.", "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.", "The Medical Journal of Australia Internet peer-review study.", "Effect of open peer review on quality of reviews and on reviewers' recommendations: a randomised trial.", "Open peer review: a randomised controlled trial.", "Publication bias and meta-analyses: a practical example.", "Does masking author identity improve peer review quality? A randomized controlled trial. PEER Investigators." ]

[ "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 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.", "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).", "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.", "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.", "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.", "Publication bias is widely appreciated, but considerable time and effort are needed to locate and obtain data from unpublished randomized controlled trials (RCTs), those published in non-English language journals or those reported in the gray literature; for this publication, we will call this collection of trials the \"gray+literature.\" However, excluding such trials from systematic reviews could introduce bias and give rise to misleading conclusions.\n We aimed to explore and quantify the impact of inclusion of gray+ literature on the results of all completed individual patient data (IPD) reviews coordinated by our group (13 meta-analyses). For each IPD review, results were calculated for RCTs fully published in English language journals and RCTs fully published in English language journals and the gray+literature.\n The IPD meta-analyses based only on RCTs that were fully published in English language journals tended to give more favorable results than those that included RCTs from the gray+literature. Although in most cases the addition of gray+data gave less encouraging results, moving the estimated treatment effect toward a null result, the direction of effect was not always predictable.\n We recommend that all systematic reviews should at least attempt to identify trials reported in the gray+literature and, where possible, obtain data from them.", "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." ]

[ "9531581", "7760868", "8683249", "7048657", "6790985", "10735900", "11841402", "910806", "8605328" ]

[ "A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).", "Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B.", "Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group.", "Prophylactic granulocyte transfusions: results of a randomized controlled trial in patients with acute myelogenous leukemia.", "A controlled trial of prophylactic granulocyte transfusions during initial induction chemotherapy for acute myelogenous leukemia.", "Use of recombinant human granulocyte colony-stimulating factor to increase chemotherapy dose-intensity: a randomized trial in very high-risk childhood acute lymphoblastic leukemia.", "Efficacy of granulocyte colony-stimulating factor in the treatment of acute myelogenous leukaemia: a multicentre randomized study.", "A controlled study of the efficacy of granulocyte transfusions in patients with neutropenia.", "A randomized phase-III study of the efficacy of granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia. Berlin-Frankfurt-Münster Study Group." ]

[ "The complete remission (CR) rate after intensive chemotherapy for acute myelogenous leukemia (AML) remains low in elderly patients, mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy, and to shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5 micrograms/kg/d by 6-hour intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to the induction course. Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or not a consolidation course before maintenance therapy. The CR rate was similar in the GM-CSF and placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of resistant disease, and rate of regrowth of leukemia were also similar in both groups. The time to neutrophil recovery was shorter in patients who received GM-CSF (24 v 29 days; P = .0001), but the incidence and characteristics of infectious events were not different. The 2-year disease-free survival (DFS) rate was significantly improved in the GM-CSF group (48% v 21% in the placebo group; P = .003). This effect was highly significant in the cohort of patients aged 55 to 64, but only marginal in patients >/=65 years of age. There was a trend toward a longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the administration of GM-CSF, concomitantly with chemotherapy and thereafter during induction course in AML, shortened the time to neutrophil recovery, but did not improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These results are promising and further evaluation of myeloid growth factors in AML is warranted.", "Elderly patients with primary acute myelogenous leukemia (AML) are less likely to enter remission than younger adults, in part because of a higher mortality rate related to severe myelosuppression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to shorten the duration of neutropenia and decrease infectious complications when administered after chemotherapy to patients with lymphomas and solid tumors.\n We randomly assigned 388 patients 60 years of age or older who had newly diagnosed primary AML to receive placebo or GM-CSF (5 micrograms per kilogram of body weight per day intravenously over a period of six hours) in a double-blind manner, beginning the day after the completion of three days of daunorubicin (45 mg per square meter of body-surface area per day) and seven days of cytarabine (200 mg per square meter per day by continuous intravenous infusion). If leukemia cells persisted in the marrow three weeks after the initiation of chemotherapy, further daunorubicin (two days) and cytarabine (five days) were administered. GM-CSF or placebo was given daily until the neutrophil count was at least 1000 per cubic millimeter, there was evidence of the regrowth of leukemia, or severe toxic effects attributable to the study infusion occurred. Patients who had a complete remission were then randomly assigned to receive one of two intensification regimens.\n Of 388 patients (median age, 69 years), 193 were randomly assigned to receive GM-CSF and 195 to placebo. The rate of complete remission was 51 percent (95 percent confidence interval, 44 to 59 percent) among those assigned to GM-CSF and 54 percent (95 percent confidence interval, 47 to 61 percent) among those assigned to receive placebo (P = 0.61). The reasons for failure (early death, death during marrow hypoplasia, and persistent leukemia), the incidence of severe or lethal infection, and the incidence of the regrowth of leukemia (2 percent overall) were similar in the two groups. The median duration of neutropenia was slightly shorter (P = 0.02) in the patients who received GM-CSF (15 days) than in those who received placebo (17 days), but the clinical importance of this result was minimal because the growth factor failed to lower the treatment-related mortality rate or improve the rate of complete remission.\n GM-CSF, in the dose and schedule we used, does not stimulate the regrowth of leukemia, but it also does not decrease the severe myelosuppressive consequences of initial chemotherapy or improve the response rate in patients 60 years of age or older with primary AML. It should not be recommended for use in such patients.", "To assess the value of granulocyte-macrophage colony-stimulating factor (GM-CSF) for induction treatment of acute myeloid leukemia (AML), both for priming of leukemic cells and for acceleration of hematopoietic recovery.\n GM-CSF was administered 5 micrograms/kg/d by continuous intravenous (i.v.) infusion during induction therapy with daunorubicin (DNR) (days 1 to 3) and cytarabine (ARA-C) (days 1 to 7). A total of 102 patients were randomized onto four arms, as follows: (1) GM-CSF 24 hours before and during chemotherapy (arm +/-); (2) GM-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes (PMNs) (arm -/+);(3) GM-CSF before, during, and after chemotherapy (arm +/+); or (4) no GM-CSF (arm -/-). Stopping rules were applied in case of an initial WBC count greater than 30 x 10(9)/L or a secondary increase of circulating blast cells. Analyses were performed according to the intention-to-treat principle.\n The complete remission (CR) rates were 77% (arm -/-), 72% (arm +/-), 48% (arm -/+), and 46% (arm +/+). Patients randomized to receive GM-CSF after induction (arms -/+ and +/+) had a significantly lower CR rate (P = .008) and a trend toward accelerated recovery of neutrophils, but no fewer infections or induction deaths. The lower CR rate appeared to be related to an increased resistance rate, with persistent leukemia. The main side effects of GM-CSF were fluid retention and hypotension.\n GM-CSF administered during induction treatment of AML with a DNR/Ara-C combination did not provide any clinical benefit. Furthermore, there was a significant decrease in the CR rate with more persistent leukemia when GM-CSF was administered during the hypoplastic phase after the chemotherapy courses.", "A prospective randomized and controlled clinical trial of prophylactic granulocyte transfusions was conducted in an attempt to reduce the mortality from infection in newly diagnosed adults with acute myelogenous leukemia. Granulocytes were harvested from normal donors by cytapheresis, and transfused patients received a median of 1.45 x 10(10) granulocytes (range 0.28--3.45 x 10(10)) on alternate days during marrow aplasia caused by initial induction chemotherapy. Transfusion were started if the absolute peripheral granulocyte count was less than 500 microliters. Thirteen patients received from one to 12 granulocyte transfusions, and 11 control patients received no granulocytes. No significant advantage was demonstrated in the transfused patients compared with controls with regard to the following: 1) deaths due to infection, 2) reduction in the frequency of febrile episodes, 3) delay in the onset of fever, 4) reduction in the length of febrile episodes, or 5) reduction in the frequency of proven infection.", "To evaluate the role of prophylactic granulocyte transfusions during remission-induction chemotherapy for acute myelogenous leukemia (AML) we randomized 102 infected patients either to receive daily granulocyte transfusions when blood granulocytes fell below 0.5 x 10(9) per liter (54 patients) or not to receive them (48). Although the percentage of patients acquiring any infection was similar in the transfusion and control groups (46 and 42 per cent, respectively), granulocyte transfusions decreased the proportion of patients with bacterial septicemia (9 per cent of those with transfusions vs. 27 per cent of the controls; P = 0.01). Granulocyte transfusions did not reduce the incidence of other infections or improve bone-marrow recovery, remission rate and duration, or survival. Seventy-two per cent of the patients given transfusions had transfusion reactions. Pulmonary infiltrates were more common in the transfusion group than in the control group (57 per cent vs. 27 per cent; P = 0.002). Thirty-five per cent of the patients with pulmonary filtrates died, as compared with 5 per cent of those without filtrates. We conclude that prophylactic granulocyte transfusions should not be used during remission-induction chemotherapy in AML because the risks outweigh the benefits.", "To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL).\n Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval).\n CDI was significantly increased in the G-CSF group compared with the non-G-CSF group (mean +/- 95% confidence interval, 105 +/- 5% v 91 +/- 4%; P <.001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups.\n G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.", "To investigate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in patients with acute myelogenous leukaemia, a multicentre randomized study was performed. From October 1993 to September 1996, 270 patients with newly diagnosed acute myelogenous leukaemia were randomized to G-CSF or control groups after remission induction therapy. The G-CSF group received G-CSF (Filgrastim) from 48 h after the completing chemotherapy until the absolute neutrophil count exceeded 1.5 x 10(9)/l. The control group did not receive G-CSF unless severe infection occurred. There were 245 evaluable patients (120 and 125 in the G-CSF and control groups respectively). The complete remission rate was similar in the G-CSF and control groups (80.8% versus 76.8%), as was the 5-year probability of disease-free survival (34.5% versus 33.6%) and overall survival (42.7% versus 35.6%). Neutrophil recovery was significantly faster in the G-CSF group than in the control group (12 d versus 18 d, P = 0.0001). The median duration of febrile neutropenia was significantly shorter in the G-CSF group than in the control group (3 d versus 4 d, P = 0.0001). In conclusion, prophylactic administration of G-CSF after remission induction therapy for acute myelogenous leukaemia is safe and useful even in patients without infection on completing chemotherapy.", "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.", "Overall chemotherapeutic treatment results in pediatric acute lymphoblastic leukemia (ALL) are good, with event-free survival (EFS) rates over 70%. However, for a subset of patients characterized by high-risk (HR) features the outcome is less favorable, with EFS rates below 50%. Intensification of chemotherapy may improve the outcome for those patients, but increased toxicity, particularly myelosuppression, limits the escalation of dose intensity. Recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF) is known to reduce myelosuppression after cancer chemotherapy in adults. The objective of this study was to examine the effect of r-metHuG-CSF on myelosuppression in HR pediatric ALL patients and on the overall response rate to chemotherapy. Patients with HR pediatric ALL were randomized to receive nine alternating cycles of chemotherapy according to the German ALL-Berlin-Frankfurt-Münster 90 protocol either alone or followed by r-metHuG-CSF administered prophylactically at a dose of 5 microg/kg/d subcutaneously. In both groups, the planned interval between chemotherapy courses was a minimum of 21 days. We report here interim results of 34 patients. The incidence of febrile neutropenia (absolute neutrophil count <0.5 x 10(9)/L and oral temperature > or = 38.5 degrees C) was 17% in children receiving r-metHuG-CSF, as compared with 40% in the control group (P = .007). In addition, the median total duration of febrile neutropenia was reduced from 20.3 to 6.2 days per patient (P = .02). Culture-confirmed infections occurred less frequently in the r-metHuG-CSF group (8% v 15%; P = .04), and the total duration of intravenous antibiotic use was significantly reduced from 32.2 days to 18.2 days per patient (P = .02). A tighter adherence to the planned treatment schedule was also facilitated by r-metHuG-CSF (P = .007). With a median follow-up of 3.3 years, the estimated EFS of 4 years is 41% +/- 12%. In conclusion, r-metHuG-CSF administered prophylactically in the interval between chemotherapy courses significantly reduced febrile neutropenia, culture-confirmed infections, and duration of intravenous antibiotic administration and allowed for tighter adherence to the treatment schedule." ]

[ "14965404", "9779530", "1535495", "15770171", "19967572", "15507794", "8162479", "15207999", "17908562" ]

[ "Implementation of RCGP guidelines for acute low back pain: a cluster randomised controlled trial.", "Capacity of the clinical picture to characterize low back pain relieved by facet joint anesthesia. Proposed criteria to identify patients with painful facet joints.", "Controlled trial of balneotherapy in treatment of low back pain.", "Implementation of the Dutch low back pain guideline for general practitioners: a cluster randomized controlled trial.", "Two psychological interventions are effective in severely disabled, chronic back pain patients: a randomised controlled trial.", "Early intervention for the management of acute low back pain: a single-blind randomized controlled trial of biopsychosocial education, manual therapy, and exercise.", "Low level laser therapy is ineffective in the management of rheumatoid arthritic finger joints.", "A randomized controlled clinical trial for low back pain treated by acupressure and physical therapy.", "Comparison of a functional restoration program with active individual physical therapy for patients with chronic low back pain: a randomized controlled trial." ]

[ "The Royal College of General Practitioners (RCGP) has produced guidelines for the management of acute low back pain in primary care.\n To investigate the impact on patient management of an educational strategy to promote these guidelines among general practitioners (GPs).\n Group randomised controlled trial, using the health centre as the unit of randomisation.\n Primary care teams in north-west England.\n Twenty-four health centres were randomly allocated to an intervention or control arm. Practices in the intervention arm were offered outreach visits to promote national guidelines on acute low back pain, as well as access to fast-track physiotherapy and to a triage service for patients with persistent symptoms.\n Twenty-four centres were randomised. Two thousand, one hundred and eighty-seven eligible patients presented with acute low back pain during the study period: 1049 in the intervention group and 1138 in the control group. There were no significant differences between study groups in the proportion of patients who were referred for X-ray, issued with a sickness certificate, prescribed opioids or muscle relaxants, or who were referred to secondary care, but significantly more patients in the intervention group were referred to physiotherapy or the back pain unit (difference in proportion = 12.2%, 95% confidence interval [CI] = 2.8% to 21.6%).\n The management of patients presenting with low back pain to primary care was mostly unchanged by an outreach educational strategy to promote greater adherence to RCGP guidelines among GPs. An increase in referral to physiotherapy or educational programmes followed the provision of a triage service.", "Prospective randomized study to compare the efficacy of facet joint injection with lidocaine and facet joint injection with saline in two groups of patients with low back pain, with and without clinical criteria that were determined in a previous study to implicate the facet joint as the primary source of the pain.\n To assess the efficacy of single facet joint anesthesia versus placebo (saline injections) and to determine clinical criteria that are predictive of significant relief of LBP after injection.\n There is no syndrome that discriminates between lower back pain caused by facet joint and that caused by other structures. Single or double facet joint anesthesia, and single photon emission computed tomography are expensive and time-consuming procedures for selecting patients in controlled clinical trials with large populations.\n Results of a previous study showed that seven clinical characteristics were more frequent in patients who responded to facet joint anesthesia than in those who did not. In the current study, a group of 43 patients with lower back pain who met at least five criteria were compared with 37 patients who met fewer criteria. Patients randomly received injection of either lidocaine or saline into the lower facet joints. The result was considered positive if more than 75% pain relief was determined by visual analog scale. The patient, the radiologist, and the investigator were blinded. An analysis of variance was used to seek an interaction between clinical group effect and injection effect, and logistic regression analysis to select the best set of variables that would be predictive of minimum pain relief of 75% after the injection.\n There was a significant interaction between clinical group and injection effect (P = 0.003). In patients with back pain, lidocaine provided greater lower-back pain relief than saline (P = 0.01). Lidocaine also-provided greater pain relief in the back pain group than in the nonpain group (P = 0.02). The presence of five among seven variables (age greater than 65 years and pain that was not exacerbated by coughing, not worsened by hyperextension, not worsened by forward flexion, not worsened when rising from flexion, not worsened by extension-rotation, and well-relieved by recumbency), always including the last item, distinguished 92% of patients responding to lidocaine injection and 80% of those not responding in the lidocaine group.\n A set of five clinical characteristics can be used in randomized studies to select lower back pain that will be well relieved by facet joint anesthesia. These characteristics should not, however, be considered as definite diagnostic criteria of lower back pain originating from facet joints.", "Three treatments for non-specific lumbar pain--balneotherapy, underwater traction bath, and underwater massage--were assessed in a randomised prospective controlled trial in 158 outpatients. Each group was treated for four weeks and patients were reviewed at the end of this period and at 12 months after entry to the trial. The prescription of analgesics and the pain score were significantly reduced in all three treated groups, but there was no difference between the three groups. No significant change occurred in spinal motion and the straight leg raising test. After one year only the analgesic consumption was significantly lower than in the control group.", "Cluster randomized controlled trial for a multifaceted implementation strategy.\n To assess the effectiveness of tailored interventions (multifaceted implementation strategy) to implement the Dutch low back pain guideline for general practitioners with regard to adherence to guideline recommendations.\n Guidelines for the management of low back pain in primary care have been developed in various countries, but little is known about the optimal implementation strategy. A multifaceted implementation strategy was developed to overcome identified barriers to the implementation of the Dutch low back pain guideline for general practitioners.\n General practitioners were randomized to an intervention or a control group. The general practitioners in the intervention group (n = 21) received tailored interventions consisting of the Dutch low back pain guideline for general practitioners, a 2-hour educational and clinical practice workshop; two scientific articles on low back pain management; the guideline for occupational physicians; a tool for patient education; and a tool for reaching agreement on low back care with physical, exercise, and manual therapists. The control group (n = 20) received no intervention. The participating general practitioners were asked to recruit consecutive patients with a new episode of low back pain as the main reason for consultation. General practitioners completed registration forms of each individual consultation with regard to the main outcome measures: advice and information, referral to other health-care providers, and prescription of medication.\n Forty-one of the 67 randomized general practitioners reported on a total of 616 consultations for 531 patients with nonspecific low back pain. The advice and explanation provided by the general practitioners, the prescription of paracetamol or nonsteroidal anti-inflammatory drugs, and prescription of pain medication on atime contingent or a pain contingent basis showed no statistically significant differences between the intervention and control groups. There were also no differences in overall referral rate. However, in follow-up consultations fewer patients were referred to a physical or exercise therapist by the general practitioners in the intervention group than in the control group.\n The multifaceted intervention strategy modestly improved implementation (for parts of the recommendations in) the Dutch low back pain guideline by general practitioners and produced small concomitant changes in patient management. The implementation strategy produced fewer referrals to therapists during follow-up consultations.", "Many pain patients appreciate biofeedback interventions because of the integration of psychological and physiological aspects. Therefore we wanted to investigate in a sample of chronic back pain patients whether biofeedback ingredients lead to improved outcome of psychological interventions.\n One hundred and twenty-eight chronic back pain patients were randomly assigned to cognitive-behavioural therapy (CBT), cognitive-behavioural therapy including biofeedback tools (CBT-B) or waitlist control (WLC). The sample was recruited from a highly disabled group including many patients with low education status and former back surgeries. Measures on pain, physical functioning, emotional functioning, coping strategies and health care utilisation were taken at pretreatment, posttreatment and 6 months of follow-up.\n The results indicated significant improvements on most outcome measures for CBT-B and CBT in comparison to WLC. CBT-B and CBT were equally effective (e.g. ITT effect sizes for pain intensity: CBT-B, 0.66 (95% CI 0.39-0.95); CBT, 0.60 (95% CI 0.33-0.87)).\n In conclusion, biofeedback ingredients did not lead to improved outcome of a psychological intervention. Cognitive-behavioural treatment as a \"package\" of respondent, operant and cognitive interventions was effective for ameliorating pain-related symptoms for chronic back pain patients treated in an outpatient setting. The high treatment acceptability associated with biofeedback ingredients can also be achieved with pure psychological interventions.", "A single blind randomized controlled trial comparing two models of care for patients with acute simple low back pain.\n To compare two research-based models of care for acute low back pain and investigate the effect of the timing of physical intervention.\n National guidelines offer conflicting information on the delivery of physical treatment in the management of acute low back pain. The guidelines suggest two different models of care. Direct comparisons between these models are lacking in the literature. The present study aims to compare these approaches to the management of acute low back pain.\n Among 804 referred patients, 102 subjects met the specific admission criteria and were randomly assigned to an \"assess/advise/treat\" group or an \"assess/advise/wait\" group. The intervention consisted of biopsychosocial education, manual therapy, and exercise. Assessment of short-term outcome enables comparison to be made between intervention and advice to stay active. Assessment of long-term outcome enables comparison to be made between early and late intervention. Study outcomes of reported pain (Visual Analogue Scale), functional disability (the Roland and Morris Disability Questionnaire), mood (Modified Zung Self Rated Depression Score, Modified Somatic Perception Questionnaire, State-Trait Anxiety Inventory), general health (Euroqol), and quality of life (Short Form 36) were assessed at baseline, 6 weeks, 3 months, and 6 months.\n At 6 weeks, the assess/advise/treat group demonstrated greater improvements in disability, mood, general health, and quality of life than patients in the assess/advise/wait group (P < 0.05). Disability and pain were not significantly different between the groups at long-term follow up (P > 0.05). However, mood, general health, and quality of life remained significantly better in the assess/advise/treat group (P < 0.05).\n At short-term, intervention is more effective than advice on staying active, leading to more rapid improvement in function, mood, quality of life, and general health. The timing of intervention affects the development of psychosocial features. If treatment is provided later, the same psychosocial benefits are not achieved. Therefore, an assess/advise/treat model of care seems to offer better outcomes than an assess/advise/wait model of care.", "Low level laser therapy (LLLT) is a relatively new and increasingly popular form of electrotherapy. It is used by physiotherapists in the treatment of a wide variety of conditions including RA despite the lack of scientific evidence to support its efficacy. A randomized, double-blind and placebo-controlled study was conducted to evaluate the efficacy of LLLT. The patient sample consisted of chronic RA patients with active finger joint synovitis. Forty RA patients with involvement of some or all of MCP or PIP joints were recruited. Following random allocation they received either active or placebo laser three times a week for 4 weeks. Measurements were taken prior to entry, after the treatment, 1 month and 3 months at follow-up. The groups were well matched in terms of age, sex, disease duration and severity. Few significant differences were noted in grip strength, duration of morning stiffness, joint tenderness, temperature of inflamed joints, range of movement or pain either within or between groups. Using these irradiation parameters the efficacy of LLLT is ineffective.", "Although acupressure has been reported to be effective in managing various types of pain, its efficacy in relieving pain associated with low back pain (LBP) remains unclear. The aim of this study is to compare the efficacy of acupressure with that of physical therapy in reducing low back pain.\n A randomized controlled clinical trial in an orthopedic referral hospital in Taiwan was conducted between December 20, 2000, and March 2, 2001. A total of 146 participants with chronic low back pain were randomly assigned to the acupressure group (69) or the physical therapy group (77), each with a different treatment technique. Self-appraised pain scores were obtained before treatment as baseline and after treatment as outcomes using the Chinese version of Short-Form Pain Questionnaire (SF-PQ).\n There were no significant differences in baseline characteristics among patients randomized into the two groups. The mean of posttreatment pain score after a 4-week treatment (2.28, SD = 2.62) in the acupressure group was significantly lower than that in the physical therapy group (5.05, SD = 5.11) (P = 0.0002). At the 6-month follow-up assessment, the mean of pain score in the acupressure group (1.08, SD = 1.43) was still significantly lower than that in the physical therapy group (3.15, SD = 3.62) (P = 0.0004).\n Our results suggest that acupressure is another effective alternative medicine in reducing low back pain, although the standard operating procedures involved with acupressure treatment should be carefully assessed in the future.\n Copyright 2004 The Institute for Cancer Prevention and Elsevier Inc.", "To compare the short-term outcomes of active individual therapy (AIT) with those of a functional restoration program (FRP).\n Prospective randomized controlled study.\n Two rehabilitation centers and private ambulatory physiotherapy facilities.\n One hundred thirty-two adults with chronic low back pain. Fifty-one percent of patients on sick leave or out of work (mean duration, 180d in the 2y before treatment).\n For 5 weeks, FRP (at 25h/wk) or AIT (at 3h/wk).\n Trunk flexibility, back flexor, and extensor endurance (Ito and Sorensen tests), general endurance, pain intensity, Dallas Pain Questionnaire (DPQ) scores, daily activities, anxiety depression, social interest, and work and leisure activities, and self-reported improvement (work ability, resumption of sport and leisure activities).\n All outcome measures improved after treatment except endurance in AIT. There was no between-group difference for pain intensity or DPQ daily activities or work and leisure activities scores. Better results were observed in FRP for all other outcome measures. There was a significant effect of treatment and the initial value for the gain of the Sorensen score with a treatment or initial value interaction; a significant effect of treatment and initial value on the gains of Ito, endurance, and DPQ social interest and anxiety depression scores, with no treatment or initial value interaction; and a significant effect of initial value but not treatment for the gains of DPQ daily activities and work and leisure activities scores.\n Low-cost ambulatory AIT is effective. The main advantage of FRP is improved endurance. We speculate that this may be linked to better self-reported work ability and more frequent resumption of sports and leisure activities." ]

[ "17786128", "12441803", "20515418", "15909273", "20163349", "15630469", "19036752", "16527165", "18977721" ]

[ "A randomized controlled trial of therapeutic drug monitoring in treatment-naive and -experienced HIV-1-infected patients.", "PharmAdapt: a randomized prospective study to evaluate the benefit of therapeutic monitoring of protease inhibitors: 12 week results.", "Abacavir/lamivudine/zidovudine maintenance after standard induction in antiretroviral therapy-naïve patients: FREE randomized trial interim results.", "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.", "Results of a community-based antiretroviral treatment program for HIV-1 infection in Western Uganda.", "Randomized, controlled trial of therapy interruption in chronic HIV-1 infection.", "High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients.", "[Clinical trial comparing efficacy and safety of four highly active antiretroviral therapy (HAART) in antiretroviral-naive treatment with advanced HIV infection].", "Virologic, immunologic, clinical, safety, and resistance outcomes from a long-term comparison of efavirenz-based versus nevirapine-based antiretroviral regimens as initial therapy in HIV-1-infected persons." ]

[ "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.", "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", "Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested. We performed a randomized, open-label, multicenter, 96-week comparative study in antiretroviral therapy (ART)-naïve patients with CD4 <or=350 cells/mm(3) and HIV-1 RNA concentrations (viral load [VL]) greater than 30,000 copies per milliliter. Patients were randomized after reaching VL less than 50 copies per milliliter on two consecutive occasions between 12 and 24 weeks after start of zidovudine/lamuvidine and lopinavir/ritonavir combination. Eligible subjects switched to abacavir/lamivudine/zidovudine (TZV) or continued the PI-containing regimen. Here we present the 48-week data with virologic success rate (failure: VL > 50 copies per milliliter). Two hundred seven patients had similar baseline (BL) characteristics: median CD4 180 cells/mm(3), median VL 5.19 log(10) copies per milliliter. One hundred twenty subjects (58%) met randomization criteria. Baseline VL differed significantly between dropouts and randomized subjects (median 5.41 versus 5.06 log(10) copies per milliliter, p = 0.017), as did CD4 cells (median 160 and 200 cells/mm(3), p = 0.044). Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI. At week 48, 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression (log rank test; p = 0.379). CD4 counts increased significantly in both arms. In ART-naïve patients, TZV maintenance had similar antiviral efficacy compared to continued standard ART at 48 weeks after baseline. Patients on successful standard ART can be safely switched to a NRTI-only regimen, at least for the tested time period.", "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 compare the treatment outcomes and mortality in a rural community-based ART (CBART) program with a hospital-based ART program in the same district.\n The study design was a non-randomized cohort study consisting of 185 persons living with HIV (PLWHIV) in the CBART cohort and 200 PLWHIV in the hospital cohort. Eligibility for both cohorts was: being HIV-infected and eligible for ART, being treatment naïve, age 18 years or older, and being a resident of Rwimi sub-county. The intervention consisted of a community-based program which included weekly home visits to patients by trained volunteers who delivered antiretroviral drugs (ARVs), monitored and supported adherence to treatment, and identified and reported adverse reactions and other clinical symptoms. Outcome variables were compared to patients in a hospital-based cohort who received the standard care delivered to all other HIV patients in the hospital. The main outcome measures were HIV-1 RNA viral load (VL), CD4 cell count and mortality after six months of treatment.\n Successful ART treatment outcome as measured by virological suppression (VL<400 copies/ml) in the CBART cohort were similar to those in the hospital-based cohort (90.1% vs 89.3%, p=0.47). The median CD4 cell count increased significantly in both cohorts (community-based cohort 159 cells/microl vs 145 cells/microl in the hospital-based cohort). Mortality was not significantly different in both cohorts (community-based cohort 11.9%, hospital-based cohort 9.0%).\n The findings show that outcomes of a CBART intervention in a rural area compare favorably to outcomes of hospital-based care. If the study results are sustainable over a longer time period, this model could be considered for ART roll-out to impoverished rural/remote populations in Uganda and elsewhere.", "Approaches to limiting exposure to antiretroviral therapy (ART) drugs are an active area of HIV therapy research. Here we present longitudinal follow-up of a randomized, open-label, single-center study of the immune, viral, and safety outcomes of structured therapy interruptions (TIs) in patients with chronically suppressed HIV-1 infection as compared to equal follow-up of patients on continuous therapy and including a final therapy interruption in both arms.\n Forty-two chronically HIV-infected patients on suppressive ART with CD4 counts higher than 400 were randomized 1:1 to either (1) three successive fixed TIs of 2, 4, and 6 wk, with intervening resumption of therapy with resuppression for 4 wk before subsequent interruption, or (2) 40 wk of continuous therapy, with a final open-ended TI in both treatment groups. Main outcome was analysis of the time to viral rebound (>5,000 copies/ml) during the open-ended TI. Secondary outcomes included study-defined safety criteria, viral resistance, therapy failure, and retention of immune reconstitution. There was no difference between the groups in time to viral rebound during the open-ended TI (continuous therapy/single TI, median [interquartile range] = 4 [1-8] wk, n = 21; repeated TI, median [interquartile range] = 5 [4-8] wk, n = 21; p = 0.36). No differences in study-related adverse events, viral set point at 12 or 20 wk of open-ended interruption, viral resistance or therapy failure, retention of CD4 T cell numbers on ART, or retention of lymphoproliferative recall antigen responses were noted between groups. Importantly, resistance detected shortly after initial viremia following the open-ended TI did not result in a lack of resuppression to less than 50 copies/ml after reinitiation of the same drug regimen.\n Cycles of 2- to 6-wk time-fixed TIs in patients with suppressed HIV infection failed to confer a clinically significant benefit with regard to viral suppression off ART. Also, secondary analysis showed no difference between the two strategies in terms of safety, retention of immune reconstitution, and clinical therapy failure. Based on these findings, we suggest that further clinical research on the long-term consequences of TI strategies to decrease drug exposure is warranted.", "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.", "Comparison of efficacy and safety of four highly active antiretroviral therapy regimens (HAART) including two nucleoside analogues (NA) and a protease inhibitor (PI) in HIV positive patients with advanced infection and antiretroviral naive.\n Multicenter, randomized and open labeled clinical trial in ten community hospitals of Castilla-La Mancha and Madrid. Regimen 1 contains zidovudine (AZT), lamivudine (3TC) and indinavir (IDV) regimen 2 includes AZT, 3TC and ritonavir (RTV), regimen 3 was didanosine (DDI), estavudine (D4T) and IDV, and regimen 4 included DDI, D4T and RTV. Decrease in viral load of HIV (VC) has been assessed as primary endpoint and as secondary one, the increase of the numbers of CD4 lymphocytes, percentage of disease progression, adverse reactions and adherence. Measurements were made at baseline visit and at 6, 12, 24, 36 and 48 weeks.\n A total of 98 patients with a mean baseline CD4 count of 122 x 10(6)/l (range of 5-340) and a baseline viral load of 5.1 log copies/ml were included. At 48 weeks, a mean increase of the CD4 and decrease of the viral load without significant difference between the 4 regimens (103 cells/2.62 log in regimen 1; 169 cells/2.86 log in regimen 2; 171 cells/2.56 log in regimen 3 and 141 cells/1.71 log in regimen 4) were observed in the analysis of the patients in treatment. Treatment was discontinued due to adverse reactions: 24% in regimen 1, 48% in regimen 2, 26% in regimen 3 and 32% in regimen 4, without significant difference. Analyzing by PI groups, 41% of the patients with RTV and 25% of those with IDV discontinued treatment due to adverse effects. There was withdrawal from treatment due to disease progression in 7% of the RTV patients and in 9% of IDV patients.\n In the HIV positive patients with advanced infection, efficacy between the four regimens of HAART is similar, but there is a tendency to require more withdrawal due to adverse effects in the RTV group than in those of IDV, the two used as single PI.", "To compare long-term virologic, immunologic, and clinical outcomes in antiretroviral-naïve persons starting efavirenz (EFV)- versus nevirapine (NVP)-based regimens.\n The FIRST study randomized patients into three strategy arms: PI+NRTI, NNRTI+NRTI, and PI+NNRTI+NRTI. NNRTI was determined by optional randomization (NVP or EFV) or by choice. For this randomized substudy, the primary endpoint was HIV RNA >50 copies/mL after 8 months or death. Genotypic resistance testing was done at virologic failure (VF; HIV RNA >1,000 copies/mL at or after 4 months).\n 228 persons (111 randomized to EFV, 117 to NVP) were followed for median 5 years. Rates per 100 person years for the primary endpoint were 41.2 (EFV) and 42.8 (NVP; p = .59). The percent of persons with HIV RNA <50 copies/mL was similar throughout follow-up (p = .24), as were average increases in CD4+ cells (p = .30). 423 persons declining the substudy chose EFV; 264 chose NVP. There were 915 persons in the combined cohort (randomized and choice). In the combined cohort, the risk of VF and VF with any NNRTI or NRTI resistance or resistance of any class was significantly less for EFV compared to NVP.\n EFV-based regimens as initial therapy resulted in a lower risk of VF and VF with resistance than did NVP-based regimens, although immunologic and clinical outcomes were similar." ]

[ "9668994", "11286448", "9457018", "17563512", "15910477", "16170976", "17668972", "11113795", "16685298" ]

[ "The effect of extraction of third molars on late lower incisor crowding: a randomized controlled trial.", "Role of antimicrobials in third molar surgery: prospective, double blind,randomized, placebo-controlled clinical study.", "Anteroposterior skeletal and dental changes after early Class II treatment with bionators and headgear.", "Clinical and radiographic evaluation of implant-retained mandibular overdentures with immediate loading.", "Endodontic complications after plastic restorations in general practice.", "Clinical trial of a novel interdental brush cleaning system.", "Efficacy of an automated flossing device in different regions of the mouth.", "Short-term effects of fiberotomy on relapse of anterior crowding.", "Comparison of two chlorhexidine rinse protocols on the incidence of alveolar osteitis following the surgical removal of impacted third molars." ]

[ "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.", "To test the efficacy of two dosing regimens of antimicrobial prophylaxis during the removal of impacted lower third molars.\n Double blind, prospective, placebo-controlled trial.\n Teaching hospital, India.\n 151 patients aged 19-36 having impacted lower third molars removed.\n Random allocation into three groups: placebo (n= 34), metronidazole 1g orally, 1 hour preoperatively (n= 44), or metronidazole 400mg orally eight hourly for 5 days postoperatively (n= 47). Patients were recalled on the sixth postoperative day for assessment of pain scores on the second and sixth days, swelling, differences in mouth opening between preoperative and the sixth postoperative day, and the state of the wound.\n There were no significant differences in the outcome between the three groups (P= 0.09).\n Antimicrobial prophylaxis does not seem to reduce morbidity after removal of lower third molars.\n Copyright 2001 The British Association of Oral and Maxillofacial Surgeons.", "In this study we examined anteroposterior cephalometric changes in children enrolled in a randomized controlled trial of early treatment for Class II malocclusion. Children, aged 9.6 +/- 0.8 years at the start of study, were randomly assigned to control (n = 81), bionator (n = 78), and headgear/biteplane (n = 90) treatments. Cephalograms were obtained initially, after Class I molars were obtained or 2 years had elapsed, after an additional 6 months during which treated subjects were randomized to retention or no retention and after a final 6 months without appliances. Calibrated examiners, blinded to group, used Johnston's analysis to measure anteroposterior cephalometric changes. Statistical analysis was used to determine annual skeletal and dental changes during treatment, retention, and follow-up, and overall. Our data reveal that both bionator and head-gear treatments corrected Class II molar relationships, reduced overjets and apical base discrepancies, and caused posterior maxillary tooth movement. The skeletal changes, largely attributable to enhanced mandibular growth in both headgear and bionator subjects, were stable a year after the end of treatment, but dental movements relapsed.", "The aim of this study was to evaluate and compare immediate-loaded implant-retained mandibular overdentures and delayed-loaded implant-retained mandibular overdentures.\n Ten completely edentulous male patients received 40 dental implants. Patients were randomly divided into 2 equal groups, 5 patients each. Patients of both groups received conventional maxillary complete denture and had stage 1 surgery for placing 4 dental implant fixtures, 2 on each side anterior to the mental foramina. Group A: One-stage surgical procedure and immediate loading. Patients in this group received mandibular bar-retained overdenture supported by 4 endosseous implants loaded immediately after implant placement. Group B: The original 2-stage concept and delayed loading. Patients in this group received mandibular bar-retained overdenture supported by 4 endosseous implants that remained submerged for a period of 4 months before loading. The patients were evaluated clinically and radiographically immediately after overdenture delivery and after 6 months, 12 months, 18 months, and 24 months.\n The results of clinical evaluation showed no statistical significant difference between the 2 groups regarding the effect of treatment. The radiographic assessment showed no statistical significant difference in mesial and distal alveolar bone loss at the different intervals of the follow-up period, except at the 12-month period, where immediately loaded implants showed a decrease in the amount of alveolar bone loss mesially and distally compared to delayed loaded implants.\n The results suggest that immediate-loaded implants provide promising results compared to delayed-loaded implants and can be a possible alternative procedure in implant dentistry.", "To test the hypothesis that dentine and pulp protection by conditioning-and-sealing is no less effective than using a conventional calcium hydroxide lining.\n A cohort of healthy adults requiring a new or replacement restoration in a posterior tooth was recruited in six general practices. All procedures received local Ethics Committee approval. Exclusion criteria included signs and symptoms of pulp necrosis or inflammation, and patients unable to commit to a long-term trial. Cavity preparations were randomized to receive a calcium hydroxide lining or conditioning-and-sealing with a smear-removing bonding system. Choice of bulk restorative material (composite resin or amalgam) was at the discretion of the dentist. The key outcome measure was evidence of pulpal breakdown identified at unscheduled (emergency) or scheduled recall examinations. Postoperative sensitivity was recorded on 100 mm VAS at 24 h, 4 days and 7 days. Pulp status was assessed at 6, 12, 24 and 36 month recall, and at any emergency recall appointment. The relationship between pre-treatment and treatment variables and pulp breakdown was assessed by logistic regression (P = 0.05).\n A total of 602 teeth were recruited, with comparable numbers of cavities lined (288, 47.8%) or conditioned and sealed (314, 52.2%). The majority (492, 81.7%) were replacement restorations, and amalgam was the most common bulk restorative material (377, 62.6%). A total of 390 (64.8%) restored teeth were reviewed at 6 months, 307 (51%) at 12 months, 363 (60.3%) at 24 months, and 279 (46.3%) at 36 months post-restoration. Sixteen cases of pulp breakdown were identified within 36 months of restoration placement, 11 presenting as emergencies and five detected at routine recall examination. Logistic regression showed that preoperative pain, cavity treatment by lining or conditioning-and-sealing and the use of rubber dam isolation had no association with pulp breakdown. Pulp breakdown was associated with deep or pulpally exposed cavities (P < 0.001, odds ratio 7.8) and with composite rather than amalgam restorations (P = 0.001, odds ratio 2.13). Re-coding to identify teeth with pulp exposures revealed that pulpal exposure was the key determinant of adverse pulp outcomes (P < 0.0001, odds ratio 28.4) and that composite resin restorations were again more likely to be associated with pulp breakdown than amalgam (P = 0.017, odds ratio 3.92).\n Considered within the context of routine primary dental care: Dentists can be confident that pulps will be equally well protected from post-restorative breakdown up to 36 months by calcium hydroxide lining and conditioning-and-sealing with adhesive resins. Residual dentine thickness appears to be a key determinant of pulp responses after restorative dental treatment. In deep and pulpally exposed cavities in posterior teeth, composites were associated with more pulpal breakdown than amalgams.", "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.", "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 effects of fiberotomy were evaluated in alleviating dental relapse of incisors after orthodontic treatment. The study sample consisted of 23 patients with crowded maxillary and mandibular incisors before orthodontic treatment. The amount of initial crowding was determined according to Little's irregularity index. Fiberotomy procedures were performed on 11 of the patients 1 week before debonding. The other 12 subjects served as the control group. All patients wore Hawley retainers. Lateral cephalometric headfilms and dental casts of the patients were taken at the beginning (T1) and at the end (T2) of treatment, 6 months into the retention phase (T3), and 1 year after orthodontic treatment (T4). Significant increase of irregularity index was noted in the control group at T3 and T4 for both maxillary and mandibular anterior segments (P <.05, P <.01). Meanwhile, in the group where circumferential supracrestal fiberotomy was performed, no significant increase of the irregularity index was noted.", "Alveolar osteitis (dry socket) is the most common complication following the extraction of permanent teeth. This study was undertaken to compare the effect of two chlorhexidine rinse protocols on the incidence of alveolar osteitis in patients undergoing surgical removal of impacted mandibular third molar teeth.\n A prospective randomized clinical trial was conducted among 99 subjects. Patients were randomly assigned into two groups. Subjects were instructed to rinse twice daily with 15 ml of chlorhexidine rinse 30 seconds for one week before and one week after surgery (group I) or one week after surgery (group II). Postoperatively, all patients were instructed to return in one week or sooner if bothersome pain increased or persisted. Data were collected regarding abnormal healing, presence of necrotic tissue, exposed bone, and absence of clot.\n The results indicated group I and group II were not statistically significant different in the reduction of alveolar osteitis.\n To reduce alveolar osteitis after impacted third molar surgery, it was observed use of postoperative chlorhexidine rinse was adequate. The postoperative use of chlorhexidine is more feasible than both preoperative and postoperative use." ]

[ "10474848", "17066964", "16643264", "17513815", "11689579", "9638782", "12096294", "18603157", "11343530" ]

[ "A group cognitive behaviour therapy programme with metastatic breast cancer patients.", "Randomized clinical trial on cognitive therapy for depression in women with metastatic breast cancer: psychological and immunological effects.", "Does routine assessment and real-time feedback improve cancer patients' psychosocial well-being?", "Impact of a peer-delivered telephone intervention for women experiencing a breast cancer recurrence.", "Randomized trial of coordinated psychosocial interventions based on patient self-assessments versus standard care to improve the psychosocial functioning of patients with cancer.", "Reducing distress in cancer patients with an orientation program.", "Intervention to improve psychological functioning for newly diagnosed patients with cancer.", "Management of depression for people with cancer (SMaRT oncology 1): a randomised trial.", "Supportive-expressive group therapy and distress in patients with metastatic breast cancer: a randomized clinical intervention trial." ]

[ "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.", "Depression is particularly prevalent in patients with advanced cancer. Cognitive therapy (CT) is an empirically supported treatment for depression in the general population. However, efficacy remains to be demonstrated in patients with advanced cancer. A prior controlled trial of CT in a group format showed improvements in depression, mood disturbance, and self-esteem; however, these effects were not maintained over time. Studies examining the efficacy of individual format CT interventions that may ensure more long-term maintenance of benefits are necessary. This study assessed the efficacy of CT for depression administered individually in women with metastatic breast cancer and its effect on immune function.\n Forty-five women were randomly assigned to either individual CT or to a waiting-list control (WLC) condition. CT was composed of eight weekly sessions of CT and three booster sessions administered at 3-week intervals following the end of treatment.\n Patients treated with CT had significantly lower scores on the Hamilton Depression Rating Scale at posttreatment compared to untreated patients. Pooled data from both groups indicated significant reductions of depressive symptoms from pre- to posttreatment, as well as reduction of associated symptoms including anxiety, fatigue, and insomnia symptoms. These effects were well sustained at the 3- and 6-month follow-up evaluations. CT for depression did not appear to have a significant impact on immune functioning.\n Findings of this study support the efficacy of CT for depression in this population and suggest that the administration of individual and booster sessions after treatment termination may be instrumental in sustaining the treatment effects over time.", "This study examined the effectiveness of giving medical oncologists immediate feedback about cancer patients' self-reported psychosocial well-being in reducing those patients' levels of anxiety, depression, perceived needs and physical symptoms. Cancer patients attending one cancer centre for their first visit were allocated to intervention (n = 42) or control (n = 38) groups. All patients completed a computerized survey assessing their psychosocial well-being while waiting to see the oncologist. Intervention patients' responses were immediately scored and summary reports were placed in each patient's file for follow-up. A total of 48 participants (25 intervention and 23 control) completed the survey four times. Intervention patients who reported a debilitating physical symptom at visit 2 were significantly less likely to report a debilitating physical symptom at visit 3 compared with control patients (OR = 2.8, P = 0.04). Reductions in levels of anxiety, depression and perceived needs among intervention patients were not significantly different to control patients. Repeated collection and immediate feedback of patient-reported health information to oncologists has potential to improve patients' symptom control, but has little impact upon emotional well-being, including those at high risk. Future research should consider providing the feedback to other health professionals and patients, and monitor the impact on the process of individual patient care.", "A first breast cancer recurrence creates considerable distress, yet few psychosocial interventions directed at this population have been reported. The Southwest Oncology Group conducted a phase III randomized trial to evaluate the effectiveness of a brief telephone intervention.\n Three hundred five women experiencing a first recurrence of breast cancer were randomly assigned to standard care or intervention. The intervention consisted of four to eight telephone calls delivered over a 1-month period. The calls were conducted by trained peer counselors at a breast cancer advocacy organization, the Y-ME National Breast Cancer Organization, and followed a standard curriculum. Psychosocial distress (Cancer Rehabilitation Evaluation System-Short Form [CARES-SF]) and depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) outcomes were assessed at baseline and 3 and 6 months. The 3-month assessment was the primary end point and is the focus of this article.\n Analysis revealed no differences in distress or depressive symptoms at 3 months between the intervention and control groups; at 3 months, 70% of control patients and 66% of intervention patients reported psychosocial distress, and 40% of control patients and 47% of intervention patients exhibited depressive symptoms.\n Telephone peer counseling did not lead to better psychosocial outcomes. The persistent distress in these women supports the urgent need for the development and testing of more intensive or different supportive interventions for this group of patients.", "To determine whether making patient-reported cancer needs, quality-of-life (QOL), and psychosocial information available to the health care team, allowing coordinated specifically targeted psychosocial interventions, resulted in reduced cancer needs, improved QOL, and increased satisfaction with care received.\n Self-reported cancer needs, QOL, and psychosocial information was collected from 450 people with cancer, using standardized questionnaires via a touch-screen computer. For a randomly chosen two thirds, this information was made available to the health care team who coordinated targeted psychosocial interventions. Information from the remaining one third was not seen. Patients were assessed 2 and 6 months after randomization for changes in their cancer needs, QOL, and psychosocial functioning and satisfaction with overall care received.\n There were no significant differences between the two arms with respect to changes in cancer needs, QOL, or psychosocial functioning between the baseline and follow-up assessments, nor with respect to satisfaction with care. However, for the subgroup of patients who were moderately or severely depressed at baseline, there was a significant reduction in depression for the intervention arm relative to the control arm at the 6-month assessment (P =.001).\n Making patient-reported cancer needs, QOL, and psychosocial data available to the health care team at a single consultation together with coordinated psychosocial interventions does not seem to reduce cancer needs nor improve QOL, psychosocial functioning, or satisfaction with the care received. However, identification of patients with moderate or severe levels of depression may be valuable in reducing subsequent levels of depression.", "The purpose of this study was to test a brief orientation program for reducing anxiety, depressive symptoms, and overall distress in cancer patients at their initial clinic visit. One hundred and fifty consecutively referred patients seen in an oncology outpatient clinic were randomly assigned to an intervention or usual care control group. The intervention group received a clinic tour, general information about clinic operations, and a question and answer session with an oncology counselor. Outcome measures included the State-Trait Anxiety Inventory (STAI), the Brief Profile of Mood States (POMS), the Center for Epidemiologic Studies-Depression (CES-D) Scale, and an oncology clinic questionnaire which were administered at the initial clinic visit and follow-up. There were no statistically significant clinical or demographic differences between groups at initial assessment. At follow-up, the intervention group had lower state anxiety, lower overall distress, and fewer patients reporting depressive symptoms. Patients in the intervention group demonstrated significantly more knowledge about clinic operations and greater satisfaction with care. These data provide evidence that anxiety, distress and depressive symptoms can be reduced with an orientation program. This finding has particular relevance in the early stages of diagnosis where patients may suffer symptoms of anxiety and depression.", "To test the effects of a computer-based nursing intervention designed to provide patients and family caregivers with concrete, objective information on symptom management; provide education about disease and treatment; coordinate medical resources; and provide emotional support and counseling.\n Two-site, randomized clinical trial.\n A large, urban, midwestern, tertiary-cancer center and a community-based cancer center in a medium-sized midwestern city.\n 109 patients newly diagnosed with breast, colon, or lung cancer who were receiving chemotherapy; 54 received standard care, and 55 participated in the intervention group.\n Outcome data were collected via structured telephone interviews at three time points: baseline, midway through the intervention, and one month postintervention. The intervention consisting of nine visits, five in person and four by telephone, was conducted over 18 weeks by advanced practice oncology nurses.\n Psychosocial functioning, anxiety, and depression.\n Patients who received the intervention had significantly less depression between baseline and the midway point, as well as less anxiety and greater improvement in the role-emotional and mental health subscales of the Medical Outcomes Study 36 Short Form.\n Cancer-care nursing interventions can decrease psychosocial morbidity and improve quality of life for newly diagnosed patients with cancer undergoing treatment. Additional research is needed to understand who benefited most from the intervention.\n This nurse-directed intervention resulted in improved mental health for patients; however, physical subscales were not changed. Further work is needed to determine why depression and mental health were affected yet physical health and symptoms did not differ between groups. Results support the important role of nurses in addressing mental health issues in patients and families experiencing cancer.", "Major depressive disorder severely impairs the quality of life of patients with medical disorders such as cancer, but evidence to guide its management is scarce. We aimed to assess the efficacy and cost of a nurse-delivered complex intervention that was designed to treat major depressive disorder in patients who have cancer.\n We did a randomised trial in a regional cancer centre in Scotland, UK. 200 outpatients who had cancer with a prognosis of greater than 6 months and major depressive disorder (identified by screening) were eligible and agreed to take part. Their mean age was 56.6 (SD 11.9) years, and 141 (71%) were women. We randomly assigned 99 of these participants to usual care, and 101 to usual care plus the intervention, with minimisation for sex, age, diagnosis, and extent of disease. The intervention was delivered by a cancer nurse at the centre over an average of seven sessions. The primary outcome was the difference in mean score on the self-reported Symptom Checklist-20 depression scale (range 0 to 4) at 3 months after randomisation. Analysis was by intention to treat. This trial is registered as ISRCTN84767225.\n Primary outcome data were missing for four patients. For 196 patients for whom we had data at 3 months, the adjusted difference in mean Symptom Checklist-20 depression score, between those who received the intervention and those who did not, was 0.34 (95% CI 0.13-0.55). This treatment effect was sustained at 6 and 12 months. The intervention also improved anxiety and fatigue but not pain or physical functioning. It cost an additional pound sterling 5278 (US$10 556) per quality-adjusted life-year gained.\n The intervention-Depression Care for People with Cancer-offers a model for the management of major depressive disorder in patients with cancer and other medical disorders who are attending specialist medical services that is feasible, acceptable, and potentially cost effective.", "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." ]

[ "7954233", "2200559", "9620330", "8609071", "11896097", "18242076", "11981766", "17058027", "10738212" ]

[ "Treatment of liver metastases from colorectal cancer with hepatic artery occlusion, intraportal 5-fluorouracil infusion, and oral allopurinol. A randomized clinical trial.", "Prospective randomized controlled trial of hepatic arterial embolization or infusion chemotherapy with 5-fluorouracil and degradable starch microspheres for colorectal liver metastases.", "Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution.", "A prospective randomized trial of the preventive effect of pre-operative transcatheter arterial embolization against recurrence of hepatocellular carcinoma.", "Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy--an intergroup study.", "Multicentre randomised phase III trial comparing Tamoxifen alone or with Transarterial Lipiodol Chemoembolisation for unresectable hepatocellular carcinoma in cirrhotic patients (Fédération Francophone de Cancérologie Digestive 9402).", "Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.", "Efficacy of postoperative transarterial chemoembolization and portal vein chemotherapy for patients with hepatocellular carcinoma complicated by portal vein tumor thrombosis--a randomized study.", "Limited but definite efficacy of prophylactic hepatic arterial infusion chemotherapy after curative resection of colorectal liver metastases: A randomized study." ]

[ "Regional therapy for colorectal liver metastases aimed at prolonging survival has not been tested fully in a randomized trial with untreated control subjects. This study explored the efficacy of temporary hepatic artery occlusion followed by intraportal infusion of 5-fluorouracil (5-FU) and oral allopurinol as biochemical modulators in prolonging the survival of patients with nonresectable liver metastases and no extrahepatic cancer.\n Eighty-four patients were considered for randomization, of whom 24 were excluded at laparotomy because of extrahepatic cancer (n = 17) or resectable lesions (n = 5). In two patients, no cancer was identified in the liver. Thirty-two patients were allocated to receive treatment, and 28 were allocated to receive no regional or systemic treatment. Six patients were excluded after randomization because of major protocol violations.\n The median survival time for patients was 17 months (range, 0-66), and for control subjects, the median was 8 months (range, 0-31). Log rank analysis demonstrated a significant survival benefit for treatment versus no treatment (P = 0.0039). (In two patients, early death was due to toxicity from the wrong dose of 5-FU and the wrong route of administration, respectively; the mean and median survival were reduced by 1 month).\n This study identified a treatment modality that prolongs survival in patients with nonresectable liver metastases and no extrahepatic metastases from colorectal cancer, suggesting that control subjects receiving no therapy may not be necessary in future randomized trials.", "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.", "This randomized, controlled trial assessed the effect of transarterial embolization (TAE) (without associated chemotherapy) on the survival of patients with nonsurgical hepatocellular carcinoma (HCC). Eighty consecutive patients were randomized to treatment with embolization (Group A, n = 40), or to symptomatic treatment (Group B, n = 40), there being no differences between both groups regarding the degree of liver function impairment and tumor stage. Eighty-two percent of the patients presented a self-limited postembolization syndrome, without treatment-related mortality. Fifty-five percent of the treated cases exhibited a partial response, which resulted in a lower probability of tumor progression during follow-up (57% vs. 77% at 1 year; P < .005). However, after a median follow-up of 24 months (30 deaths in each group), there are no differences in survival (Group A: 49% and 13%; Group B: 50% and 27%, at 2 and 4 years, respectively; P = .72). The absence of differences was maintained even when dividing patients according to Child-Pugh's grade, Okuda stage, or performance status test (PST). Furthermore, there were no differences in the probability of complications or in the need of hospital admissions. In conclusion, TAE has a marked antitumoral effect associated to a slower growth of the tumor, but it does not improve the survival of patients with nonsurgical HCC.", "To clarify whether pre-operative transcatheter arterial embolization (TAE) improves survival after hepatectomy, a prospective randomized comparative study was done. Of a total of 115 registered patients having solitary hepatocellular carcinoma (HCC) 2 to 5 cm in diameter, 18 (15.7%) were excluded after randomization. As a result, 97 patients were chosen as subjects and divided into two groups: hepatectomy with (group A: n=50) and without (group B: n=47) pre-operative TAE. The period of observation of the patients who survived the surgery was between 4.0 and 6.6 years. The randomization appeared to have provided well-balanced groups of patients and the clinico-pathological characteristics of the two groups were quite similar. The necrotic part of the cancerous lesions, as confirmed by operative specimens, amounted to 74.8+/-33.4% (mean +/-SD) in group A and 6.8+/-7.2% in group B (P<0.01). However, the cancer-free survival rates after hepatectomy in both groups showed little difference (39.1+/-7.0 (%+/-SE) and 31.1+/-0.1, respectively). We speculate that TAE is not effective against such HCC accessory lesions as minute intrahepatic metastasis and tumor thrombus and that pre-operative TAE does not improve post-operative survival.", "Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated.\n Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival.\n The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P =.04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P =.03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P =.60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P =.19)\n These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer.", "The FFCD 9402 multicentre phase III trial was designed to compare the effects of the combination of Transarterial Lipiodol Chemoembolisation (TACE) and tamoxifen with tamoxifen alone on overall survival and quality of life in the palliative treatment of hepatocellular carcinoma with cirrhosis. From 1995 to 2002, 138 patients were randomised between the two groups. One hundred and twenty three patients were eligible including 61 in the Tamoxifen group and 62 in the TACE group. Baseline characteristics were similar: Child-Pugh class A: 70%, alcoholic cirrhosis: 76%, Okuda stage I: 71%, multinodular tumour: 70% and segmental portal vein thrombosis: 10%. At 2years, the overall survival was 22% and 25% in the Tamoxifen and TACE groups (P=.68), respectively. Multivariate analysis identified four independent prognostic factors for survival: alpha-fetoprotein (AFP)>400ng/mL (P=.008), abdominal pain (P=.011), hepatomegaly (P=.023) and Child-Pugh score (P=.032). The Spitzer Index level assessing the quality of life during follow-up did not differ between the two groups (P=.70). Amongst patients with stage Okuda I, the 2-year overall survival was 28% in the Tamoxifen group and 32% in the TACE group (P=.58). In this subgroup, two prognostic factors were statistically significant for survival: AFP>400ng/mL (P=.004) and Spitzer Index (P=.013) as shown by multivariable analysis. In conclusion, this study suggests that TACE improves neither the survival nor the quality of life in patients with HCC and cirrhosis.", "This randomized, controlled trial assessed the efficacy of transarterial Lipiodol (Lipiodol Ultrafluide, Laboratoire Guerbet, Aulnay-Sous-Bois, France) chemoembolization in patients with unresectable hepatocellular carcinoma. From March 1996 to October 1997, 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and randomly were assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery (chemoembolization group, 40 patients) or symptomatic treatment (control group, 40 patients). One patient assigned to the control group secondarily was excluded because of unrecognized systemic metastasis. Chemoembolization was repeated every 2 to 3 months unless there was evidence of contraindications or progressive disease. Survival was the main end point. The chemoembolization group received a total of 192 courses of chemoembolization with a median of 4.5 (range, 1-15) courses per patient. Chemoembolization resulted in a marked tumor response, and the actuarial survival was significantly better in the chemoembolization group (1 year, 57%; 2 years, 31%; 3 years, 26%) than in the control group (1 year, 32%; 2 years, 11%; 3 years, 3%; P =.002). When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model, the survival benefit of chemoembolization remained significant (relative risk of death, 0.49; 95% CI, 0.29-0.81; P =.006). Although death from liver failure was more frequent in patients who received chemoembolization, the liver functions of the survivors were not significantly different. In conclusion, in Asian patients with unresectable hepatocellular carcinoma, transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment.", "The aim of this single, randomized study was to explore the efficacy of postoperative transarterial chemoembolization (TACE) and portal vein chemotherapy (PVC) for patients with hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombosis (PVTT) and to evaluate prognostic factors.\n The study cohort consisted of 112 patients with HCC and PVTT randomly divided into three groups: Group A (37 patients), operation only; Group B (35 patients), operation plus TACE; Group C (40 patients), operation plus TACE and PVC. Disease-free survival rates and prognostic factors were analyzed.\n Most of the side effects and complications were related to the operation, catheters, and local chemotherapy and included liver decompensation (15.0%), catheter obstruction (11.6%), and nausea and loss of appetite (22.1%). The disease-free survival curve was significantly different among the three groups, as estimated by the Kaplan-Meier method (both P < 0.05). Group C showed a significantly higher disease-free survival rate than Group A (P < 0.05), but no statistical differences were found between group A and group B, and group B and group C (both P > 0.05). Tumor size, tumor number, PVTT location, and treatment modalities were independent prognostic factors (P < 0.05).\n Postoperative TACE combined with PVC may benefit the survival of patients with HCC complicated by PVTT in the short-term (less than 60 months), but long-term efficacy is not yet certain and needs to be confirmed by further studies.", "Greater than 50% of patients who undergo curative resection of liver metastases from colorectal carcinoma develop recurrent disease in the residual liver. Although several studies have attempted to use hepatic arterial infusion (HAI) chemotherapy to prevent recurrence, to the authors' knowledge the efficacy of the treatment has not yet been determined.\n Nineteen patients who underwent curative hepatectomy for metastatic colorectal carcinoma randomly were assigned into the HAI group (nine patients) or the control group (ten patients). Patients in the HAI group received continuous intraarterial infusion of 5-fluorouracil (5-FU) (500 mg/day) for 4 days followed by a 3-day rest. The treatment was continued for 6 weeks.\n The median follow-up period was 62.2 months. The recurrence was confirmed in three patients in the HAI group and in eight patients in the control group. Of these, recurrence in the remnant liver was observed in one patient and in six patients, respectively. The median disease free interval after hepatectomy was 62.6 months in the HAI group and 13.8 months in the control group. The 1-year, 2-year, and 3-year disease free survival rates were 77.8%, 77.8%, and 66.7%, respectively, in the HAI group and 50.0%, 30.0%, and 20.0%, respectively, in the control group. Significant prolongation of disease free survival was observed in the HAI group (P = 0.045). No patients in the HAI group reported any adverse effect of >/= Grade 2 (according to the National Cancer Institute Common Toxicity Criteria). Two patients in the HAI group and five patients in the control group were dead of disease at the time of last follow-up. The 1-year, 3-year, and 5-year cumulative survival rates for the HAI group were 88.9%, 77.8%, and 77.8%, respectively, whereas those of the control group were 100.0%, 50.0%, and 50.0%, respectively (P = 0.2686).\n This randomized study revealed that short term HAI of 5-FU after curative resection of colorectal hepatic metastases is effective in preventing the recurrence of disease without any serious complications.\n Copyright 2000 American Cancer Society." ]

[ "8545227", "9386673", "9652561", "1651610", "8920706", "9002329", "16148848", "15602194", "1326741" ]

[ "Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines--report of the National Multicenter Trial. United States Rotavirus Vaccine Efficacy Group.", "Efficacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations.", "Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis.", "Immunogenicity and safety of rhesus-human rotavirus reassortant vaccines with serotype 1 or 2 VP7 specificity.", "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.", "Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant rotavirus vaccine in Belém, Brazil.", "Evaluation of safety, immunogenicity and efficacy of an attenuated rotavirus vaccine, RIX4414: A randomized, placebo-controlled trial in Latin American infants.", "Efficacy of RIX4414 live attenuated human rotavirus vaccine in Finnish infants.", "Protective efficacy against serotype 1 rotavirus diarrhea by live oral rhesus-human reassortant rotavirus vaccines with human rotavirus VP7 serotype 1 or 2 specificity." ]

[ "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.", "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.", "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%.", "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.", "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.", "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 live attenuated monovalent rotavirus vaccine RIX4414 was developed with a human strain of G1P1A P[8] specificity to reduce the rotavirus burden in children.\n A double blind, randomized, placebo-controlled study evaluated the efficacy, immunogenicity, safety and reactogenicity of 2 oral doses of RIX4414 (10(4.7), 10(5.2) or 10(5.8) focus-forming units) at 2 and 4 months coadministered with routine vaccinations and oral poliovirus vaccine given for study purposes at least 14 days apart. The 2155 infants (1618 vaccine/537 placebo) enrolled in Brazil, Mexico and Venezuela were followed until 1 year of age.\n Antirotavirus IgA seroconversion rates 2 months after dose 2 ranged between 61% (10(4.7) ffu group) and 65% (10(5.8) ffu group), and most of the infants had seroprotective levels of antibodies to coadministered routine vaccinations. The reactogenicity profile of RIX4414 was similar to that of the placebo, and no vaccination-related serious adverse events were reported. Protective efficacy against severe and any rotavirus gastroenteritis from 15 days post-dose 2 was highest in the 10(5.8) ffu group [86%; 95% confidence interval (95% CI), 63-96% and 70% (95% CI 46-84%), P < 0.001, 2-sided Fisher's exact test]. The efficacy against hospitalization was 79% (95% CI 48-92%) for pooled vaccine groups. Multiple rotavirus serotypes [G1 (50%), G9 (40%), G2, G3 and G4] were identified from gastroenteritis stools (enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction) during the study period. For severe gastroenteritis caused by G9 serotypes, the protection reached 77% (95% CI 18-96%) in the 10(5.8) ffu group, providing proof of concept that the monovalent G1P1A P[8] human rotavirus vaccine elicits cross-protection against the G9 strain. A reduction in any and severe rotavirus gastroenteritis was already observed at post-dose 1 (period: day of dose 1 to 14 days post-dose 2) in vaccinees compared with placebo recipients.\n Two doses of RIX4414 are highly efficacious, providing cross-protection (G1 and G9 strains, prevalent during this study) and early protection against any and severe rotavirus gastroenteritis and hospitalization to infants in Latin America.", "Rotavirus gastroenteritis, a major cause of mortality and morbidity worldwide, is a vaccine-preventable disease. New safe and effective candidate rotavirus vaccines are needed to replace the withdrawn rhesus rotavirus-based oral vaccine.\n We evaluated a monovalent human rotavirus vaccine, serotype G1, strain RIX4414, for efficacy, immunogenicity and safety in a randomized, double blind, placebo-controlled trial in Finland. We randomly allocated 405 healthy infants to receive 2 doses of vaccine or placebo (ratio 2:1) at approximately 2 and 4 months of age. The infants were followed during 2 rotavirus epidemic seasons (2000-2002) for acute gastroenteritis. Rotaviruses in diarrheal stool samples were primarily detected by enzyme-linked immunosorbent assay and confirmed and G-typed by reverse transciption-polymerase chain reaction.\n The vaccine was well-tolerated. No vaccine-related serious adverse events were observed during the study period. Rotavirus IgA (enzyme-linked immunosorbent assay) seroconversion rate was 80% after 2 doses. Thirty-eight cases of rotavirus gastroenteritis were detected during the entire follow-up period; 35 of these were of the G1 type. RIX4414 vaccine significantly decreased the occurrence of any rotavirus compared with placebo. Efficacy during the first rotavirus epidemic season was 73% [95% confidence interval (95% CI), 27-91%] and 90% (95% CI 10-100%) against any and severe rotavirus gastroenteritis, respectively, and during the entire follow-up period 72% (95% CI 42-87%) against any and 85% (95% CI 42-97%) against severe rotavirus gastroenteritis (P < 0.05 for all comparisons).\n RIX4414 strain of G1 human rotavirus vaccine was well-tolerated, immunogenic and efficacious in infants against rotavirus gastroenteritis during a 2-year period. To further increase vaccine \"take\" and efficacy, a higher dose of this vaccine may be considered for future efficacy trials.", "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." ]

[ "16359741", "16895884", "17600848", "12967058", "18653121", "12823643", "12042457", "7115656", "15814873" ]

[ "Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects.", "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.", "A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease.", "Folic acid supplementation in dementia: a preliminary report.", "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.", "Behavioural responses of young anaemic Indian children to iron-folic acid supplements.", "Effect of an enriched drink on cognitive function in frail elderly persons." ]

[ "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.", "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.", "(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.", "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.", "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.", "1. Behavioural responses of young anaemic Indian children to iron-folic acid supplements were assessed in two separate studies using the Indian adaptation of Wechsler's (1967) intelligence scale for children (WISC). 2. The first study was an exploratory study in which the cognitive behaviour of 5-8-year-old children of both sexes was assessed before and after supplementation with 20 mg elemental Fe and 0.1 mg folic acid given daily for a period of 60 d. 3. The supplemented children showed a significant improvement in haemoglobin (Hb) as well as the WISC scores while the control children who did not receive any supplements failed to show an improvement either in Hb or in the WISC scores. However, within the supplemented group when the initially-anaemic children were compared with the initially-non-anaemic ones, only the 7-year-old anaemic children performed significantly poor in the tests than the non-anaemic group of the same age. The study raised the possibility that in addition to increasing the blood Hb levels, Fe-folic acid supplements may have additional benefits in improving the cognitive performance of children. 4. In the second study, cognitive behaviour of fourteen matched pairs of anaemic children in the age-range of 5-6 years was assessed before and after supplementation with 40 mg Fe and 0.2 mg folic acid given daily in two divided doses or sugar placebos for a period of 60 d. The tester did not know the groups to which each child belonged. 5. The supplemented children showed a significant improvement in Hb as well as in the verbal and performance IQ of WISC. The control children showed no improvement in Hb but their verbal IQ improved significantly. However, there was no significant improvement in their performance IQ. 6. The results indicated that Fe-folic acid supplements to anaemic children not only raised Hb levels but also improved intelligence test results, particularly in the performance section.", "Many elderly persons report that they have difficulties learning new things and remembering names, plans, and conversations. Because decreased cognitive function in elderly persons is potentially related to their poor nutritional status, provision of essential nutrients may improve cognitive function. The authors wanted to determine whether consumption of an enriched drink, including moderate doses of all essential micronutrients, improves cognitive function in frail elderly persons.\n Frail, white adults (n=101) who were aged 65 years or older with a body mass index<or=25 kg/m2 were selected for this randomized, double-blind, placebo-controlled trial. They received either an enriched drink or a placebo product for 6 months. Before and after the intervention, participants' cognitive function was assessed (word learning test [WLT], WLT delayed, category fluency [CF] for animals and professions, and recognition memory test for words [RMTW]) and blood biochemical analyses (vitamin B12, homocysteine) were performed.\n Sixty-seven residents completed the study period. After 6 months, significant differences were noted in changes of the WLT (0.9+/-0.3 vs -0.1+/-0.3; p=.014) and CF professions (1.2+/-0.7 vs -0.6+/-0.5; p=.017) in the supplement group (n=34) compared with the placebo group (n=33). No significant differences were observed in WLT delayed, RMTW, and CF animals. The plasma vitamin B12 concentration increased (105+/-50 vs 8 +/-16; p=.003) and the homocysteine concentration decreased (-6.3+/-5.9 vs -0.3+/-2.9; p=.000) in the supplement group compared with the placebo group.\n This study contributes to the evidence that nutritional supplementation may improve neuropsychological performance in frail elderly persons." ]

[ "1575558", "11328958", "17158417", "15493734", "21402642", "11335744", "11533340", "19739491", "12242586" ]

[ "Randomised trial of nutrition for preterm infants after discharge.", "Feeding preterm infants after hospital discharge: growth and development at 18 months of age.", "Posthospital discharge feeding for preterm infants: effects of standard compared with enriched milk formula on growth, bone mass, and body composition.", "Feeding with premature or infant formula in premature infants after discharge: comparison of growth and nutrition status.", "Nutrient enrichment of mother's milk and growth of very preterm infants after hospital discharge.", "Growth of preterm infants fed nutrient-enriched or term formula after hospital discharge.", "Randomized trial of nutrient-enriched formula versus standard formula for postdischarge preterm infants.", "[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." ]

[ "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 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.", "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 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.", "To determine if the addition of a multinutrient human milk fortifier to mother's milk while breastfeeding very preterm infants after hospital discharge is possible and whether it influences first-year growth.\n Of a cohort of 320 infants (gestational age: 24-32 weeks; birth weight: 535-2255 g), breastfed infants (65% [n = 207]) were randomly assigned shortly before hospital discharge to receive either unfortified (n = 102, group A) or fortified (n = 105, group B) mother's milk until 4 months' corrected age (CA). The remaining infants were bottle-fed with a preterm formula (group C). Follow-up was performed at term and at 2, 4, 6, and 12 months' CA.\n Mean duration of breastfeeding after term was not significantly different between groups A and B (11.8 and 10.6 weeks, respectively). Weight, length, and head circumference were not significantly different between groups A and B at 12 months' CA. Compared with groups A and B, infants in group C had a higher increase in weight z score until term and in length z score until 6 months' CA. At 12 months' CA, boys in group C were significantly longer and heavier compared with those in groups A and B, whereas girls in group C were longer and heavier compared with those in group A only. A higher protein intake was related to a higher serum urea nitrogen level and growth.\n Fortification of mother's milk after hospital discharge while breastfeeding very preterm infants was possible without influencing breastfeeding duration but did not significantly influence growth parameters at 1 year of age compared with unfortified mother's milk.", "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.", "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.", "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." ]

[ "17888856", "15967546", "22375972", "18568115", "12775857", "17632223", "16501756", "17154745", "17143125" ]

[ "Nicotine replacement and behavioral therapy for smoking cessation in pregnancy.", "Case studies of three pregnant smokers and their use of nicotine replacement therapy.", "A randomized trial of nicotine-replacement therapy patches in pregnancy.", "Extended use of nicotine replacement therapy to maintain smoking cessation in persons with schizophrenia.", "Clinical trial comparing nicotine replacement therapy (NRT) plus brief counselling, brief counselling alone, and minimal intervention on smoking cessation in hospital inpatients.", "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.", "[Randomized clinical trial: effectiveness of the cognitive-behavioral approach and the use of nicotine replacement transdermal patches for smoking cessation among adults in Rio de Janeiro, Brazil].", "Evaluating nicotine replacement therapy and stage-based therapies in a population-based effectiveness trial.", "The effect of a minimal intervention strategy in addition to nicotine replacement therapy to support smoking cessation in cardiovascular outpatients: a randomized clinical trial." ]

[ "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.", "To examine the barriers encountered by pregnant women who attempt to stop smoking by highlighting three women who used nicotine patches.\n A randomised-controlled trial of nicotine-replacement therapy (NRT) in the form of patches to test its acceptability for pregnant women. Ethics approval was granted despite NRT being contraindicated in Australia for pregnant women and having a low safety rating (category D) (Australian Drug Evaluation Committee, 1999). Salivary cotinine levels were used to assess nicotine exposure and provide some indicator of NRT safety. All participants were given pregnancy-specific cessation counselling, and the 20 women in the treatment arm were offered nicotine patches (15 mg/16 hr), with the option of weaning to lower strength patches if desired.\n The Women's and Children's Hospital, Adelaide, a public tertiary teaching hospital in South Australia, with almost 4000 births annually.\n 40 'high-risk' pregnant smokers who expressed interest in stopping smoking.\n As has been found in the general population, 'quit' rates with NRT use were low. Only three of the participants in this study, who became abstinent with patch use during pregnancy, were still abstinent at birth. The circumstances of two of these women, and a third woman who used patches to 'control' her smoking despite researcher advice, are detailed here. Only one of the two women 'abstinent at delivery' was still abstinent 3 months after birth, the last contact point of the study.\n Although health providers intuitively regard pregnancy as an appropriate time for women to stop smoking, the stressors during pregnancy seem to militate against cessation. This study does not indicate that use of NRT will provide an easier solution. It may be more fruitful to institute a concerted lifestyle approach with both the woman and her partner (or significant household members), and continue this support and education postnatally if cessation has not been achieved. Health professionals should also support better-targeted public health campaigns and tobacco-control initiatives generally, because, undoubtedly, the social environment is a major determinant of initiation and continuation of smoking.", "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.).", "This study was designed to determine the feasibility and efficacy of long-term nicotine replacement therapy (NRT) in helping persons with schizophrenia remain tobacco-free. Fifty smokers with a diagnosis of schizophrenia or schizo-affective disorder and whose symptoms had been stable for at least two months were enrolled in a program providing group support and NRT (patches) in individually adjusted doses set to maintain baseline nicotine intake. All participants attended weekly group support/motivation sessions. Smoking activity was determined by measuring carbon monoxide levels in expired air. Participants who quit tobacco use completely during the first three months were entered into a single-blind phase in which they received either placebo or active nicotine patches for up to six additional months, along with biweekly group sessions. Sixty days into the open-label phase, 66% of the subjects had reduced their use of tobacco by at least 75%. After 90 days of open-label treatment, 18 subjects (36%) were tobacco-free and qualified to enter the six-month, single-blind phase, eight on placebo and nine on active patches. A significantly greater proportion of those on placebo (8 of 8) compared with those on active patches (3 of 9) relapsed prior to completion of the 6-month period. This difference is statistically significant at the p = 0.009 level. The results of this study indicate that long-term use of NRT is feasible and effective for sustained tobacco-free success and may be an important strategy for reducing health risks due to tobacco use in this special population.", "Guidelines recommend that smoking cessation interventions are offered in all clinical settings to all smokers willing to make a quit attempt. Since the effectiveness of routine provision of behavioural counselling and nicotine replacement therapy (NRT) to smokers admitted to hospital has not been established, a randomised controlled trial of these interventions given together compared with counselling alone or minimal intervention was performed in hospital inpatients.\n Medical and surgical inpatients who were current smokers at the time of admission were randomised to receive either usual care (no additional advice at admission), counselling alone (20 minute intervention with written materials), or NRT plus counselling (counselling intervention with a 6 week course of NRT). Continuous and point prevalence abstinence from smoking (validated by exhaled carbon monoxide <10 ppm) was measured at discharge from hospital and at 3 and 12 months, and self-reported reduction in cigarette consumption in smokers was assessed at 3 and 12 months.\n 274 inpatient smokers were enrolled. Abstinence was higher in the NRT plus counselling group (n=91) than in the counselling alone (n=91) or usual care (n=92) groups. The difference between the groups was significant for validated point prevalence abstinence at discharge (55%, 43%, 37% respectively, p=0.045) and at 12 months (17%, 6%, 8%, p=0.03). The respective differences in continuous validated abstinence at 12 months were 11%, 4%, 8% (p=0.25). There was no significant difference between counselling alone and usual care, or in reduction in cigarette consumption between the treatment groups.\n NRT given with brief counselling to hospital inpatients is an effective routine smoking cessation intervention.", "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.", "Randomized clinical trial carried out to investigate the effectiveness of the cognitive-behavioral approach and nicotine replacement therapy with nicotine patches for smoking cessation. Participated 1,199 adults, volunteers, in Rio de Janeiro, Brazil, randomly assigned to 10 different groups: intensive brief counseling group (GB), with 1 or 2 sessions (G1-G2), and with 3 or 4 sessions (G3-G4), with/without nicotine replacement therapy (NRT). Abstinence proportions were estimated during 12 months. These proportions among participants not assigned to NRT were 20% (GB), 17% (G1-G2), and 23% (G3-G4); and among assigned NRT groups were 30% (GBA), 34% (G1A-G2A), and 33% (G3A-G4A). After multiple adjustments, the abstinence proportions ratios seemed to follow a \"dose-response\" pattern: compared to GB, the ratios were 0.85 (G1-G2), 1.13 (G3-G4), 1.51 (GBA), 1.66 (G1A-G2A), and 1.75 (G3A-G4A). The results suggest that use of NRT increases the abstinence proportion for cessation. The \"dose-response\" pattern suggests that cognitive-behavioral could be the reasonable option in the smoking cessation therapy.", "Pharmacological interventions for smoking cessation are typically evaluated using volunteer samples (efficacy trials) but should also be evaluated in population-based trials (effectiveness trials). Nicotine replacement therapy (NRT) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New England Veterans Affairs Medical Center. Telephone interviews were completed with 3,239 smokers, and 2,054 agreed to participate (64%). Participants were randomly assigned to one of four conditions: stage-matched manuals (MAN); NRT plus manuals (NRT + MAN); expert system plus NRT and manuals (EXP + NRT + MAN); and automated counseling plus NRT, manuals, and expert system (TEL + EXP + NRT + MAN). Assessments were completed at baseline, 10, 20, and 30 months. The point prevalence cessation rates at final follow-up (30 months) were MAN, 20.3%; NRT + MAN, 19.3%; EXP + NRT + MAN, 17.6%; and TEL + EXP + NRT + MAN, 19.9%. Stage-matched manuals provided cessation rates comparable with previous studies. The addition of NRT, expert system interventions, and automated telephone counseling failed to produce a further increase in intervention effectiveness.\n ((c) 2006 APA, all rights reserved).", "Smoking is an important risk factor for recurrent events in cardiovascular patients. Evidence exists that nicotine replacement therapy (NRT) approximately doubles smoking cessation rates. The minimal intervention strategy (MIS) has been used successfully to assist patients to quit smoking in general practice, and was recently adapted for cardiology inpatients (C-MIS). It is hypothesized that in cardiovascular outpatients the combination of C-MIS and NRT significantly increases the number of quitters compared to NRT alone.\n A randomized clinical trial in 385 smoking patients who attended the cardiovascular outpatient departments in the Academic Medical Centre, Amsterdam for the treatment of atherosclerotic disease. Patients were allocated to either NRT + C-MIS or NRT alone. Self-reported and biochemically validated abstinence rates were measured at 12 months' follow-up.\n Including patients with incomplete follow-up as smokers, abstinence was reported by 19% of the NRT + C-MIS group and 14% of the NRT group [absolute risk reduction (ARR) = 0.05; 95% confidence interval (CI) = -0.02; 0.12]. According to biochemical markers, abstinence rates were 28 and 24%, respectively (ARR = 0.04, 95% CI = -0.06; 0.14). Hence, no significant differences between groups were found. The number of cigarettes smoked a day decreased significantly at 12 months: from 21 to 15 a day in the experimental group, and from 21 to 14 in the control group (P<0.001), but did not differ between groups (P=0.32).\n The effectiveness of a minimal contact intervention was investigated in order to reach as many cardiovascular patients as possible in the setting of outpatient departments. This intervention was not found to be effective." ]

[ "19673597", "20575704", "2403697", "17236918", "3324594", "10873356", "15843938", "7480237", "7648148" ]

[ "Does preoperative core needle biopsy increase surgical site infections in breast cancer surgery? Randomized study of antibiotic prophylaxis.", "Role of prophylactic antibiotics in laparoscopic cholecystectomy and risk factors for surgical site infection: a randomized controlled trial.", "A prospective, randomized double-blind study of the use of antibiotics at the time of mastectomy.", "Does prophylactic administration of systemic antibiotics prevent postoperative inflammatory complications after third molar surgery?", "Single-dose v. short-term antibiotic therapy for prevention of wound infection in general surgery. A prospective, randomized double-blind trial.", "Antibiotic prophylaxis for post-operative wound infection in clean elective breast surgery.", "Prospective, randomised study on antibiotic prophylaxis in colorectal surgery. Is it really necessary to use oral antibiotics?", "A prospective, double-blind, placebo-controlled trial of a single dose of azithromycin on postoperative wound infections in plastic surgery.", "Value of oral antibiotic prophylaxis in colorectal surgery." ]

[ "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.", "The aim of this clinical trial was to determine whether prophylactic antibiotics could prevent surgical site infection (SSI) after laparoscopic cholecystectomy and to identify any risk factors for infection.\n The study included 100 patients undergoing laparoscopic cholecystectomy. They were randomized to receive either a single dose of ceftriaxone (Group A; n = 50) or physiologic saline as placebo (Group B; n = 50) after the induction of anesthesia. Patient demographics and clinical and surgical outcomes were recorded.\n The incidence of SSI was similar in the two groups: 2 patients in group A and 4 patients in group B (chi(2) = 0.71; p = 0.40). None of the factors studied was associated with surgical site infection statistically, as shown by binary logistic regression analysis.\n A single dose of prophylactic antibiotic failed to decrease the likelihood of SSI after laparoscopic cholecystectomy.", "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.", "To estimate and compare the frequencies of inflammatory complications after third molar (M3) surgery in subjects receiving intravenous prophylactic antibiotics or saline placebo.\n Using a placebo-controlled, double-blind, randomized clinical trial, the investigators enrolled a sample composed of subjects who required extraction of at least 1 impacted M3 and requested intravenous sedation or general anesthesia. The predictor variable was treatment group classified as active treatment (penicillin or clindamycin for penicillin-allergic subjects) or placebo (0.9% saline). Study medications were randomly assigned. Both surgeon and subject were blinded to treatment assignment. The medication was administered intravenously prior to any incision. The outcome variable was postoperative inflammatory complication classified as present or absent and included alveolar osteitis (AO) or surgical site infection (SSI). Other variables were demographic, anatomic, or operative. Descriptive and bivariate statistics were computed. Statistical significance was set at P < or = .05, single-tailed test of hypothesis.\n The sample was composed of 118 subjects (n = 59 per study group). In the active treatment group, there were no postoperative inflammatory complications. In the placebo group, 5 subjects (8.5%) were diagnosed with SSI, (P = .03). No subject met the case definition for AO. All SSIs were associated with the removal of partial bony or full bony impacted mandibular M3s.\n In the setting of third molar removal, these results suggest that the use of intravenous antibiotics administered prophylactically decrease the frequency of SSIs. The authors cannot comment on the efficacy of intravenous antibiotics in comparison to other antibacterial treatment regimens, eg chlorhexidine mouthrinse or intrasocket antibiotics.", "To investigate the effectiveness of a single-dose antibiotic regimen for preventing postoperative wound infection, a prospective, randomized double-blind trial was carried out in patients undergoing \"clean-contaminated\", \"contaminated\" or \"clean\" (vascular) surgery. Both elective and emergency operations were included. Single-dose (preoperative) prophylaxis was compared with short-term prophylaxis (1 dose preoperatively and 2 doses postoperatively). The antibiotics were penicillin, tobramycin and metronidazole in various combinations, and comparisons between single-dose and short-term prophylaxis were made with all the regimens. The incidence of wound infection was 5/277 (1.8%) in the short-term group and 9/287 (3.1%) in the single-dose group. The difference was not statistically significant. Nor was statistically significant difference found when the type of operation and the degree of contamination were considered. Single-dose antibiotic prophylaxis thus gave a low incidence of postoperative wound infection, even in \"clean-contaminated\" or \"contaminated\" cases.", "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.", "The use of prophylactic antibiotics in addition to mechanical cleansing is the current standard of care prior to colonic surgery. The question of whether the antibiotics should be administered intravenously or orally, or by both routes, remains controversial. Our aim was to compare three methods of prophylactic antibiotic administration in elective colorectal surgery.\n Three hundred consecutive elective colorectal resections were studied. All patients had preoperative mechanical colon cleansing with oral sodium phosphate and intravenous antibiotic prophylaxis with cefoxitin (one dose before skin incision and two postoperative doses). Patients were randomised to one of the following three groups: group A: three doses of oral antibiotic (neomycin and metronidazole) at the time of mechanical colon cleansing; group B: one dose of oral antibiotic; group C: no oral antibiotics. All patients were followed during their hospital stay and at 7, 14 and 30 days post-surgery.\n Vomiting occurred in 31%, 11% and 9% of the studied patients (groups A, B and C, respectively) (p<0.001). Nausea was present in 44%, 18% and 13% of patients (p<0.001). Abdominal pain was recorded in 13%, 10% and 4% of patients (p: 0.077). Wound infection was present in 7%, 8% and 6% and suture dehiscence occurred in 2%, 2% and 3% of the patients in the three groups (no differences among them). Neither were differences found among the three groups in terms of urinary infections, pneumonia, postoperative ileus or intra-abdominal abscess.\n The addition of three doses of oral antibiotics to intravenous antibiotic prophylaxis is associated with lower patient tolerance in terms of increased nausea, vomiting and abdominal pain, and has shown no advantages in the prevention of postoperative septic complications. Therefore, we recommend that oral antibiotics should not be used prior to colorectal surgery.", "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.", "A total of 169 patients undergoing colorectal surgery were randomly allocated to receive either gentamicin plus metronidazole or oral ciprofloxacin plus metronidazole as prophylaxis; they were also allocated to receive cover for 1 or 3 days. Twenty-eight patients (17 per cent) developed postoperative wound infections. The proportion of patients with wound infections and other infective complications was significantly less (P < 0.02) in those receiving oral ciprofloxacin. Cover for 3 days was no better than that for only 1 day. Oral ciprofloxacin for prophylaxis may offer advantages in efficacy and ease of administration compared with parenteral antibiotics." ]