Showing papers on "Randomized controlled trial published in 2007"

Pharmacologic management of neuropathic pain: evidence-based recommendations.

Abstract: Patients with neuropathic pain (NP) are challenging to manage and evidence-based clinical recommendations for pharmacologic management are needed. Systematic literature reviews, randomized clinical trials, and existing guidelines were evaluated at a consensus meeting. Medications were considered for recommendation if their efficacy was supported by at least one methodologically-sound, randomized clinical trial (RCT) demonstrating superiority to placebo or a relevant comparison treatment. Recommendations were based on the amount and consistency of evidence, degree of efficacy, safety, and clinical experience of the authors. Available RCTs typically evaluated chronic NP of moderate to severe intensity. Recommended first-line treatments include certain antidepressants (i.e., tricyclic antidepressants and dual reuptake inhibitors of both serotonin and norepinephrine), calcium channel alpha2-delta ligands (i.e., gabapentin and pregabalin), and topical lidocaine. Opioid analgesics and tramadol are recommended as generally second-line treatments that can be considered for first-line use in select clinical circumstances. Other medications that would generally be used as third-line treatments but that could also be used as second-line treatments in some circumstances include certain antiepileptic and antidepressant medications, mexiletine, N-methyl-D-aspartate receptor antagonists, and topical capsaicin. Medication selection should be individualized, considering side effects, potential beneficial or deleterious effects on comorbidities, and whether prompt onset of pain relief is necessary. To date, no medications have demonstrated efficacy in lumbosacral radiculopathy, which is probably the most common type of NP. Long-term studies, head-to-head comparisons between medications, studies involving combinations of medications, and RCTs examining treatment of central NP are lacking and should be a priority for future research.

Reduction in Weight and Cardiovascular Disease Risk Factors in Individuals With Type 2 Diabetes: One-Year Results of the Look AHEAD Trial

Abstract: Objective: The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes one-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events. Research Design and Methods: A multi-centered randomized controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with body mass index >25 kg/m2 (>27 kg/m2 if taking insulin). An Intensive Lifestyle Intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared to a Diabetes Support and Education (DSE) condition. Results: Participants assigned to ILI lost an average 8.6% of their initial weight versus 0.7% in DSE group (p Conclusions: At 1 year, ILI resulted in clinically significant weight loss in persons with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk. Trial Registration: clinicaltrials.gov Identifier: NCT00017953

The Hawthorne Effect: a randomised, controlled trial

Abstract: The 'Hawthorne Effect' may be an important factor affecting the generalisability of clinical research to routine practice, but has been little studied. Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge, no attempt has been made to quantify them. Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia. Participants in a dementia trial were randomised to intensive follow-up (with comprehensive assessment visits at baseline and two, four and six months post randomisation) or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at six months). Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD). We recruited 176 participants, mainly through general practices. The main analysis was based on Intention to treat (ITT), with available data. In the ANCOVA model with baseline score as a co-variate, follow-up group had a significant effect on outcome at six months on the ADAS-Cog score (n = 140; mean difference = -2.018; 95%CI -3.914, -0.121; p = 0.037 favouring the intensive follow-up group), and on participant-rated quality of life score (n = 142; mean difference = -1.382; 95%CI -2.642, -0.122; p = 0.032 favouring minimal follow-up group). There was no significant difference on carer quality of life. We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia resulted in a better outcome than minimal follow-up, as measured by their cognitive functioning. Current controlled trials: ISRCTN45577048

Organised inpatient (stroke unit) care for stroke

Abstract: BACKGROUND Organised stroke unit care is provided by multidisciplinary teams that exclusively manage stroke patients in a dedicated ward (stroke, acute, rehabilitation, comprehensive), with a mobile stroke team or within a generic disability service (mixed rehabilitation ward). OBJECTIVES To assess the effect of stroke unit care compared with alternative forms of care for patients following a stroke. SEARCH STRATEGY We searched the Cochrane Stroke Group trials register (last searched April 2006), the reference lists of relevant articles, and contacted researchers in the field. SELECTION CRITERIA Randomised and prospective controlled clinical trials comparing organised inpatient stroke unit care with an alternative service. DATA COLLECTION AND ANALYSIS Two review authors initially assessed eligibility and trial quality. Descriptive details and trial data were then checked with the co-ordinators of the original trials. MAIN RESULTS Thirty-one trials, involving 6936 participants, compared stroke unit care with an alternative service; more organised care was consistently associated with improved outcomes. Twenty-six trials (5592 participants) compared stroke unit care with general wards. Stroke unit care showed reductions in the odds of death recorded at final (median one year) follow up (odds ratio (OR) 0.86; 95% confidence interval (CI) 0.76 to 0.98; P = 0.02), the odds of death or institutionalised care (OR 0.82; 95% CI 0.73 to 0.92; P = 0.0006) and death or dependency (OR 0.82; 95% CI 0.73 to 0.92; P = 0.001). Sensitivity analyses indicated that the observed benefits remained when the analysis was restricted to trials that used formal randomisation procedures with blinded outcome assessment. Outcomes were independent of patient age, sex or stroke severity, but appeared to be better in stroke units based in a discrete ward. There was no indication that organised stroke unit care resulted in a longer hospital stay. AUTHORS' CONCLUSIONS Stroke patients who receive organised inpatient care in a stroke unit are more likely to be alive, independent, and living at home one year after the stroke. The benefits were most apparent in units based in a discrete ward. No systematic increase was observed in the length of inpatient stay.

Randomized trial of laparoscopic-assisted resection of colorectal carcinoma: 3-year results of the UK MRC CLASICC Trial Group.

Abstract: Purpose The aim of the current study is to report the long-term outcomes after laparoscopic-assisted surgery compared with conventional open surgery within the context of the UK MRC CLASICC trial. Results from randomized trials have indicated that laparoscopic surgery for colon cancer is as effective as open surgery in the short term. Few data are available on rectal cancer, and long-term data on survival and recurrence are now required. Methods The United Kingdom Medical Research Council Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer (UK MRC CLASICC; clinical trials number ISRCTN 74883561) trial study comparing conventional versus laparoscopic-assisted surgery in patients with cancer of the colon and rectum. The randomization ratio was 2:1 in favor of laparoscopic surgery. Long-term outcomes (3-year overall survival [OS], disease-free survival [DFS], local recurrence, and quality of life [QoL]) have now been determined on an intention-to-treat basis. Results Seven hundred ninety-f...

Weight-loss Outcomes: A Systematic Review and Meta-Analysis of Weight-Loss Clinical Trials With a Minimum 1-year Follow-Up

Abstract: Objective To assist health professionals who counsel patients with overweight and obesity, a systematic review was undertaken to determine types of weight-loss interventions that contribute to successful outcomes and to define expected weight-loss outcomes from such interventions. Design A search was conducted for weight-loss–focused randomized clinical trials with ≥1-year follow-up. Eighty studies were identified and are included in the evidence table. Outcomes measures The primary outcomes were a measure of weight loss at 6, 12, 24, 36, and 48 months. Eight types of weight-loss interventions—diet alone, diet and exercise, exercise alone, meal replacements, very-low-energy diets, weight-loss medications (orlistat and sibutramine), and advice alone—were identified. By using simple pooling across studies, subjects mean amount of weight loss at each time point for each intervention was determined. Statistical analyses performed Efficacy outcomes were calculated by meta-analysis and provide support for the pooled data. Hedges' gu was combined across studies to obtain an average effect size (and confidence level). Results A mean weight loss of 5 to 8.5 kg (5% to 9%) was observed during the first 6 months from interventions involving a reduced-energy diet and/or weight-loss medications with weight plateaus at approximately 6 months. In studies extending to 48 months, a mean 3 to 6 kg (3% to 6%) of weight loss was maintained with none of the groups experiencing weight regain to baseline. In contrast, advice-only and exercise-alone groups experienced minimal weight loss at any time point. Conclusions Weight-loss interventions utilizing a reduced-energy diet and exercise are associated with moderate weight loss at 6 months. Although there is some regain of weight, weight loss can be maintained. The addition of weight-loss medications somewhat enhances weight-loss maintenance.

Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials.

Abstract: ContextPioglitazone is widely used for glycemic control in patients with type 2 diabetes mellitus, but evidence is mixed regarding the influence of medications of this class on cardiovascular outcomes.ObjectiveTo systematically evaluate the effect of pioglitazone on ischemic cardiovascular events.Data Sources and Study SelectionA database containing individual patient-level time-to-event data collected during pioglitazone clinical trials was transferred from the drug's manufacturer for independent analysis. Trials were included if they were randomized, double-blinded, and controlled with placebo or active comparator.Data ExtractionThe primary outcome was a composite of death, myocardial infarction, or stroke. Secondary outcome measures included the incidence of serious heart failure. A fixed-effects approach was used to combine the estimates across the duration strata and statistical heterogeneity across all the trials was tested with the I2 statistic.Data SynthesisA total of 19 trials enrolling 16 390 patients were analyzed. Study drug treatment duration ranged from 4 months to 3.5 years. Death, myocardial infarction, or stroke occurred in 375 of 8554 patients (4.4%) receiving pioglitazone and 450 of 7836 patients (5.7%) receiving control therapy (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.72-0.94; P = .005). Progressive separation of time-to-event curves became apparent after approximately 1 year of therapy. Individual components of the primary end point were all reduced by a similar magnitude with pioglitazone treatment, with HRs ranging from 0.80 to 0.92. Serious heart failure was reported in 200 (2.3%) of the pioglitazone-treated patients and 139 (1.8%) of the control patients (HR, 1.41; 95% CI, 1.14-1.76; P = .002). The magnitude and direction of the favorable effect of pioglitazone on ischemic events and unfavorable effect on heart failure was homogeneous across trials of different durations, for different comparators, and for patients with or without established vascular disease. There was no evidence of heterogeneity across the trials for either end point (I2 = 0%; P = .87 for the composite end point and I2 = 0%; P = .97 for heart failure).ConclusionsPioglitazone is associated with a significantly lower risk of death, myocardial infarction, or stroke among a diverse population of patients with diabetes. Serious heart failure is increased by pioglitazone, although without an associated increase in mortality.

Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials

Abstract: Background Ecological and observational studies suggest that low vitamin D status could be associated with higher mortality from life-threatening conditions including cancer, cardiovascular disease, and diabetes mellitus that account for 60% to 70% of total mortality in high-income countries. We examined the risk of dying from any cause in subjects who participated in randomized trials testing the impact of vitamin D supplementation (ergocalciferol [vitamin D 2 ] or cholecalciferol [vitamin D 3 ]) on any health condition. Methods The literature up to November 2006 was searched without language restriction using the following databases: PubMed, ISI Web of Science (Science Citation Index Expanded), EMBASE, and the Cochrane Library. Results We identified 18 independent randomized controlled trials, including 57 311 participants. A total of 4777 deaths from any cause occurred during a trial size–adjusted mean of 5.7 years. Daily doses of vitamin D supplements varied from 300 to 2000 IU. The trial size–adjusted mean daily vitamin D dose was 528 IU. In 9 trials, there was a 1.4- to 5.2-fold difference in serum 25-hydroxyvitamin D between the intervention and control groups. The summary relative risk for mortality from any cause was 0.93 (95% confidence interval, 0.87-0.99). There was neither indication for heterogeneity nor indication for publication biases. The summary relative risk did not change according to the addition of calcium supplements in the intervention. Conclusions Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates. The relationship between baseline vitamin D status, dose of vitamin D supplements, and total mortality rates remains to be investigated. Population-based, placebo-controlled randomized trials with total mortality as the main end point should be organized for confirming these findings.

Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis.

Abstract: ContextPharmacotherapies that augment the incretin pathway have recently become available, but their role in the management of type 2 diabetes is not well defined.ObjectiveTo assess the efficacy and safety of incretin-based therapy in adults with type 2 diabetes based on randomized controlled trials published in peer-reviewed journals or as abstracts.Data SourcesWe searched MEDLINE (1966–May 20, 2007) and the Cochrane Central Register of Controlled Trials (second quarter, 2007) for English-language randomized controlled trials involving an incretin mimetic (glucagonlike peptide 1 [GLP-1] analogue) or enhancer (dipeptidyl peptidase 4 [DPP4] inhibitor). We also searched prescribing information, relevant Web sites, reference lists and citation sections of recovered articles, and abstracts presented at recent conferences.Study SelectionRandomized controlled trials were selected if they were at least 12 weeks in duration, compared incretin therapy with placebo or other diabetes medication, and reported hemoglobin A1c data in nonpregnant adults with type 2 diabetes.Data ExtractionTwo reviewers independently assessed trials for inclusion and extracted data. Differences were resolved by consensus. Meta-analyses were conducted for several efficacy and safety outcomes.ResultsOf 355 potentially relevant articles identified, 51 were retrieved for detailed evaluation and 29 met the inclusion criteria. Incretins lowered hemoglobin A1c compared with placebo (weighted mean difference, −0.97% [95% confidence interval {CI}, −1.13% to −0.81%] for GLP-1 analogues and −0.74% [95% CI, −0.85% to −0.62%] for DPP4 inhibitors) and were noninferior to other hypoglycemic agents. Glucagonlike peptide 1 analogues resulted in weight loss (1.4 kg and 4.8 kg vs placebo and insulin, respectively) while DPP4 inhibitors were weight neutral. Glucagonlike peptide 1 analogues had more gastrointestinal side effects (risk ratio, 2.9 [95% CI, 2.0-4.2] for nausea and 3.2 [95% CI, 2.5-4.4] for vomiting). Dipeptidyl peptidase 4 inhibitors had an increased risk of infection (risk ratio, 1.2 [95% CI, 1.0-1.4] for nasopharyngitis and 1.5 [95% CI, 1.0-2.2] for urinary tract infection) and headache (risk ratio, 1.4 [95% CI, 1.1-1.7]). All but 3 trials had a 30-week or shorter duration; thus, long-term efficacy and safety could not be evaluated.ConclusionsIncretin therapy offers an alternative option to currently available hypoglycemic agents for nonpregnant adults with type 2 diabetes, with modest efficacy and a favorable weight-change profile. Careful postmarketing surveillance for adverse effects, especially among the DPP4 inhibitors, and continued evaluation in longer-term studies and in clinical practice are required to determine the role of this new class among current pharmacotherapies for type 2 diabetes.

Effects of Aerobic and Resistance Exercise in Breast Cancer Patients Receiving Adjuvant Chemotherapy: A Multicenter Randomized Controlled Trial

Abstract: Purpose Breast cancer chemotherapy may cause unfavorable changes in physical functioning, body composition, psychosocial functioning, and quality of life (QOL). We evaluated the relative merits of aerobic and resistance exercise in blunting these effects. Patients and Methods We conducted a multicenter randomized controlled trial in Canada between 2003 and 2005 that randomly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care (n = 82), supervised resistance exercise (n = 82), or supervised aerobic exercise (n = 78) for the duration of their chemotherapy (median, 17 weeks; 95% CI, 9 to 24 weeks). Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy–Anemia scale. Secondary end points were fatigue, psychosocial functioning, physical fitness, body composition, chemotherapy completion rate, and lymphedema. Results The follow-up assessment rate for our primary end point was 92.1%, and adherence to the supervised exercise was 70.2%. ...

Effectiveness of interventions to promote physical activity in children and adolescents: systematic review of controlled trials.

Abstract: Objective To review the published literature on the effectiveness of interventions to promote physical activity in children and adolescents. Design Systematic review. Data sources Literature search using PubMed, SCOPUS, Psychlit, Ovid Medline, Sportdiscus, and Embase up to December 2006. Review methods Two independent reviewers assessed studies against the following inclusion criteria: controlled trial, comparison of intervention to promote physical activity with no intervention control condition, participants younger than 18 years, and reported statistical analyses of a physical activity outcome measure. Levels of evidence, accounting for methodological quality, were assessed for three types of intervention, five settings, and three target populations. Results The literature search identified 57 studies: 33 aimed at children and 24 at adolescents. Twenty four studies were of high methodological quality, including 13 studies in children. Interventions that were found to be effective achieved increases ranging from an additional 2.6 minutes of physical education related physical activity to 283 minutes per week of overall physical activity. Among children, limited evidence for an effect was found for interventions targeting children from low socioeconomic populations, and environmental interventions. Strong evidence was found that school based interventions with involvement of the family or community and multicomponent interventions can increase physical activity in adolescents. Conclusion Some evidence was found for potentially effective strategies to increase children9s levels of physical activity. For adolescents, multicomponent interventions and interventions that included both school and family or community involvement have the potential to make important differences to levels of physical activity and should be promoted. A lack of high quality evaluations hampers conclusions concerning effectiveness, especially among children.

Psychological treatments for chronic post-traumatic stress disorder : Systematic review and meta-analysis

Abstract: Background The relative efficacy of different psychological treatments for chronic post-traumatic stress disorder (PTSD) is unclear. Aims To determine the efficacy of specific psychological treatments for chronic PTSD. Method In a systematic review of randomised controlled trials, eligible studies were assessed against methodological quality criteria and data were extracted and analysed. Results Thirty-eight randomised controlled trials were included in the meta-analysis. Trauma-focused cognitive–behavioural therapy (TFCBT), eye movement desensitisation and reprocessing (EMDR), stress management and group cognitive–behavioural therapy improved PTSD symptoms more than waiting-list or usual care. There was inconclusive evidence regarding other therapies. There was no evidence of a difference in efficacy between TFCBT and EMDR but there was some evidence that TFCBT and EMDR were superior to stress management and other therapies, and that stress management was superior to other therapies. Conclusions The first-line psychological treatment for PTSD should be trauma-focused (TFCBT or EMDR).

Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review.

Abstract: ContextSelective eligibility criteria of randomized controlled trials (RCTs) are vital to trial feasibility and internal validity. However, the exclusion of certain patient populations may lead to impaired generalizability of results.ObjectiveTo determine the nature and extent of exclusion criteria among RCTs published in major medical journals and the contribution of exclusion criteria to the representation of certain patient populations.Data Sources and Study SelectionThe MEDLINE database was searched for RCTs published between 1994 and 2006 in certain general medical journals with a high impact factor. Of 4827 articles, 283 were selected using a series technique.Data ExtractionTrial characteristics and the details regarding exclusions were extracted independently. All exclusion criteria were graded independently and in duplicate as either strongly justified, potentially justified, or poorly justified according to previously developed and pilot-tested guidelines.Data SynthesisCommon medical conditions formed the basis for exclusion in 81.3% of trials. Patients were excluded due to age in 72.1% of all trials (60.1% in pediatric populations and 38.5% in older adults). Individuals receiving commonly prescribed medications were excluded in 54.1% of trials. Conditions related to female sex were grounds for exclusion in 39.2% of trials. Of all exclusion criteria, only 47.2% were graded as strongly justified in the context of the specific RCT. Exclusion criteria were not reported in 12.0% of trials. Multivariable analyses revealed independent associations between the total number of exclusion criteria and drug intervention trials (risk ratio, 1.35; 95% confidence interval, 1.11-1.65; P = .003) and between the total number of exclusion criteria and multicenter trials (risk ratio, 1.26; 95% confidence interval, 1.06-1.52; P = .009). Industry-sponsored trials were more likely to exclude individuals due to concomitant medication use, medical comorbidities, and age. Drug intervention trials were more likely to exclude individuals due to concomitant medication use, medical comorbidities, female sex, and socioeconomic status. Among such trials, justification for exclusions related to concomitant medication use and comorbidities were more likely to be poorly justified.ConclusionsThe RCTs published in major medical journals do not always clearly report exclusion criteria. Women, children, the elderly, and those with common medical conditions are frequently excluded from RCTs. Trials with multiple centers and those involving drug interventions are most likely to have extensive exclusions. Such exclusions may impair the generalizability of RCT results. These findings highlight a need for careful consideration and transparent reporting and justification of exclusion criteria in clinical trials.

Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning.

Abstract: CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) CURRENTLY IS CONSIDERED THE MOST EFFECTIVE TREATMENT FOR OBSTRUCTIVE SLEEP APNEA (OSA) THIS device provides a pneumatic splint to prevent nocturnal airway collapse In randomized clinical trials that included use of sham CPAP as a placebo, treatment with this device has been shown to produce improvements in symptoms, quality of life, sleepiness, neuropsychological performance, and hypertension1 It has also been established that optimal effectiveness depends on consistent use Skipping even 1 night of treatment reverses improvements in daytime sleepiness, response performance, and the physiologic measure of disease severity, the apnea-hypopnea index (AHI)2–4 Although these benefits have been shown in randomized clinical trials, there is considerable variation in use of CPAP by patients in routine clinical practice,5–8 with approximately half using it consistently every night on average 6 hours per night and the other half skipping from 1 to 7 nights per week using it on average 35 hours per night5 It is not known, however, what the impact of differential use of CPAP is on effectiveness of therapy in routine clinical practice It may be that individuals with shorter hours of use are, in general, less well treated with respect to improvements in outcomes such as sleepiness, than are those with longer durations of use Alternatively, there might be individual variation in need for CPAP so that, even though some individuals have shorter hours of CPAP use, they are effectively treated with respect to sleepiness This individual variation might be mediated by biologic mechanisms similar to those of the recently described individual variation in response to sleep deprivation9 To address this question, we conducted a multisite effectiveness study in which we evaluated clinical status outcomes before and after 3 months of routine clinical care that included measurement of CPAP adherence during the entire follow-up period This multisite international study capitalized on patient heterogeneity with regard to average nightly use of CPAP, in order to estimate relationships between the likelihood of achieving a “normal” value on salient clinical measures of sleepiness and functional status and the “dose” of CPAP treatment received (ie, hours of CPAP use per night) Because there is no consensus regarding which outcomes are primary with regard to the assessment of CPAP treatment response, we chose those deemed most applicable to the clinical management of OSA—subjective sleepiness (Epworth Sleepiness Scale [ESS]10), physiologic sleepiness (Multiple Sleep Latency Test [MSLT]11), and disease-specific functional status (Functional Outcomes of Sleep Questionnaire [FOSQ]12) By evaluating the nightly duration of CPAP relative to obtaining normal values in those impaired on each of these measures, we provide data that the clinician can employ in determining optimal treatment response within the context of treatment goals, eg, to reduce daytime sleepiness, improve daily functioning, or both

Management of diabetic retinopathy: a systematic review.

Abstract: ContextDiabetic retinopathy (DR) is the leading cause of blindness in the working-aged population in the United States. There are many new interventions for DR, but evidence to support their use is uncertain.ObjectiveTo review the best evidence for primary and secondary intervention in the management of DR, including diabetic macular edema.Evidence AcquisitionSystematic review of all English-language articles, retrieved using a keyword search of MEDLINE (1966 through May 2007), EMBASE, Cochrane Collaboration, the Association for Research in Vision and Ophthalmology database, and the National Institutes of Health Clinical Trials Database, and followed by manual searches of reference lists of selected major review articles. All English-language randomized controlled trials (RCTs) with more than 12 months of follow-up and meta-analyses were included. Delphi consensus criteria were used to identify well-conducted studies.Evidence SynthesisForty-four studies (including 3 meta-analyses) met the inclusion criteria. Tight glycemic and blood pressure control reduces the incidence and progression of DR. Pan-retinal laser photocoagulation reduces the risk of moderate and severe visual loss by 50% in patients with severe nonproliferative and proliferative retinopathy. Focal laser photocoagulation reduces the risk of moderate visual loss by 50% to 70% in eyes with macular edema. Early vitrectomy improves visual recovery in patients with proliferative retinopathy and severe vitreous hemorrhage. Intravitreal injections of steroids may be considered in eyes with persistent loss of vision when conventional treatment has failed. There is insufficient evidence for the efficacy or safety of lipid-lowering therapy, medical interventions, or antivascular endothelial growth factors on the incidence or progression of DR.ConclusionsTight glycemic and blood pressure control remains the cornerstone in the primary prevention of DR. Pan-retinal and focal retinal laser photocoagulation reduces the risk of visual loss in patients with severe DR and macular edema, respectively. There is currently insufficient evidence to recommend routine use of other treatments.

Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression

Abstract: �Background Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. Methods In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined. Results Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P = 0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups. Conclusions The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder. (ClinicalTrials.gov number, NCT00012558.)

Exercise and pharmacotherapy in the treatment of major depressive disorder

Abstract: Objective To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in depression compared to placebo controls.

Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials.

Abstract: ContextHeart failure causes more than 1 million US hospitalizations yearly, mostly related to congestion. Tolvaptan, an oral, nonpeptide, selective vasopressin V2-receptor antagonist, shows promise in this condition.ObjectiveTo evaluate short-term effects of tolvaptan when added to standard therapy in patients hospitalized with heart failure.Design, Setting, and PatientsTwo identical prospective, randomized, double-blind, placebo-controlled trials at 359 sites in North America, South America, and Europe were conducted during the inpatient period of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) between October 7, 2003, and February 3, 2006. A total of 2048 (trial A) and 2085 (trial B) patients hospitalized with heart failure and congestion were studied.InterventionPatients were randomized to receive either tolvaptan (30 mg/d) or matching placebo, within 48 hours of admission.Main Outcome MeasuresPrimary end point was a composite of changes in global clinical status based on a visual analog scale and body weight at day 7 or discharge if earlier. Secondary end points included dyspnea (day 1), global clinical status (day 7 or discharge), body weight (days 1 and 7 or discharge), and peripheral edema (day 7 or discharge).ResultsRank sum analysis of the composite primary end point showed greater improvement with tolvaptan vs placebo (trial A, mean [SD], 1.06 [0.43] vs 0.99 [0.44]; and trial B, 1.07 [0.42] vs 0.97 [0.43]; both trials P<.001). Mean (SD) body weight reduction was greater with tolvaptan on day 1 (trial A, 1.71 [1.80] vs 0.99 [1.83] kg; P<.001; and trial B, 1.82 [2.01] vs 0.95 [1.85] kg; P<.001) and day 7 or discharge (trial A, 3.35 [3.27] vs 2.73 [3.34] kg; P<.001; and trial B, 3.77 [3.59] vs 2.79 [3.46] kg; P<.001), whereas improvements in global clinical status were not different between groups. More patients receiving tolvaptan (684 [76.7%] and 678 [72.1%] for trial A and trial B, respectively) vs patients receiving placebo (646 [70.6%] and 597 [65.3%], respectively) reported improvement in dyspnea at day 1 (both trials P<.001). Edema at day 7 or discharge improved significantly with tolvaptan in trial B (P = .02) but did not reach significance in trial A (P = .07). Serious adverse event frequencies were similar between groups, without excess renal failure or hypotension.ConclusionIn patients hospitalized with heart failure, oral tolvaptan in addition to standard therapy including diuretics improved many, though not all, heart failure signs and symptoms, without serious adverse events.Trial Registrationclinicaltrials.gov Identifier: NCT00071331Published online March 25, 2007 (doi:10.1001/jama.297.12.1332).

Cognitive Behavioral Therapy for Posttraumatic Stress Disorder in Women: A Randomized Controlled Trial

Abstract: ContextThe prevalence of posttraumatic stress disorder (PTSD) is elevated among women who have served in the military, but no prior study has evaluated treatment for PTSD in this population. Prior research suggests that cognitive behavioral therapy is a particularly effective treatment for PTSD.ObjectiveTo compare prolonged exposure, a type of cognitive behavioral therapy, with present-centered therapy, a supportive intervention, for the treatment of PTSD.Design, Setting, and ParticipantsA randomized controlled trial of female veterans (n=277) and active-duty personnel (n=7) with PTSD recruited from 9 VA medical centers, 2 VA readjustment counseling centers, and 1 military hospital from August 2002 through October 2005.InterventionParticipants were randomly assigned to receive prolonged exposure (n = 141) or present-centered therapy (n = 143), delivered according to standard protocols in 10 weekly 90-minute sessions.Main Outcome MeasuresPosttraumatic stress disorder symptom severity was the primary outcome. Comorbid symptoms, functioning, and quality of life were secondary outcomes. Blinded assessors collected data before and after treatment and at 3- and 6-month follow-up.ResultsWomen who received prolonged exposure experienced greater reduction of PTSD symptoms relative to women who received present-centered therapy (effect size, 0.27; P = .03). The prolonged exposure group was more likely than the present-centered therapy group to no longer meet PTSD diagnostic criteria (41.0% vs 27.8%; odds ratio, 1.80; 95% confidence interval, 1.10-2.96; P = .01) and achieve total remission (15.2% vs 6.9%; odds ratio, 2.43; 95% confidence interval, 1.10-5.37; P = .01). Effects were consistent over time in longitudinal analyses, although in cross-sectional analyses most differences occurred immediately after treatment.ConclusionsProlonged exposure is an effective treatment for PTSD in female veterans and active-duty military personnel. It is feasible to implement prolonged exposure across a range of clinical settings.Trial Registrationclinicaltrials.gov Identifier: NCT00032617

Full publication of results initially presented in abstracts

Abstract: BACKGROUND: Abstracts of presentations at scientific meetings are usually available only in conference proceedings If subsequent full publication of abstract results is based on the magnitude or direction of study results, publication bias may result Publication bias, in turn, creates problems for those conducting systematic reviews or relying on the published literature for evidence OBJECTIVES: To determine the rate at which abstract results are subsequently published in full, and the time between meeting presentation and full publication To assess the association between study characteristics and full publication SEARCH STRATEGY: We searched MEDLINE, EMBASE, The Cochrane Library, Science Citation Index, reference lists, and author files Date of most recent search: June 2003 SELECTION CRITERIA: We included all reports that examined the subsequent full publication rate of biomedical results initially presented as abstracts or in summary form Follow-up of abstracts had to be at least two years DATA COLLECTION AND ANALYSIS: Two reviewers extracted data We calculated the weighted mean full publication rate and time to full publication Dichotomous variables were analyzed using relative risk and random effects models We assessed time to publication using Kaplan-Meier survival analyses MAIN RESULTS: Combining data from 79 reports (29,729 abstracts) resulted in a weighted mean full publication rate of 445% (95% confidence interval (CI) 439 to 451) Survival analyses resulted in an estimated publication rate at 9 years of 526% for all studies, 631% for randomized or controlled clinical trials, and 493% for other types of study designs'Positive' results defined as any 'significant' result showed an association with full publication (RR = 130; CI 114 to 147), as did 'positive' results defined as a result favoring the experimental treatment (RR =117; CI 102 to 135), and 'positive' results emanating from randomized or controlled clinical trials (RR = 118, CI 107 to 130)Other factors associated with full publication include oral presentation (RR = 128; CI 109 to 149); acceptance for meeting presentation (RR = 178; CI 150 to 212); randomized trial study design (RR = 124; CI 114 to 136); and basic research (RR = 079; CI 070 to 089) Higher quality of abstracts describing randomized or controlled clinical trials was also associated with full publication (RR = 130, CI 100 to 171) AUTHORS' CONCLUSIONS: Only 63% of results from abstracts describing randomized or controlled clinical trials are published in full 'Positive' results were more frequently published than not 'positive' results

Meta-analysis of psychological interventions for chronic low back pain.

Abstract: The purpose of this meta-analysis of randomized controlled trials was to evaluate the efficacy of psychological interventions for adults with noncancerous chronic low back pain (CLBP). The authors updated and expanded upon prior meta-analyses by using broad definitions of CLBP and psychological intervention, a broad data search strategy, and state-of-the-art data analysis techniques. All relevant controlled clinical trials meeting the inclusion criteria were identified primarily through a computer-aided literature search. Two independent reviewers screened abstracts and articles for inclusion criteria and extracted relevant data. Cohen's d effect sizes were calculated by using a random effects model. Outcomes included pain intensity, emotional functioning, physical functioning (pain interference or pain-specific disability, health-related quality of life), participant ratings of global improvement, health care utilization, health care provider visits, pain medications, and employment/disability compensation status. A total of 205 effect sizes from 22 studies were pooled in 34 analyses. Positive effects of psychological interventions, contrasted with various control groups, were noted for pain intensity, pain-related interference, health-related quality of life, and depression. Cognitive-behavioral and self-regulatory treatments were specifically found to be efficacious. Multidisciplinary approaches that included a psychological component, when compared with active control conditions, were also noted to have positive short-term effects on pain interference and positive long-term effects on return to work. The results demonstrated positive effects of psychological interventions for CLBP. The rigor of the methods used, as well as the results that reflect mild to moderate heterogeneity and minimal publication bias, suggest confidence in the conclusions of this review.

Surgical versus Nonsurgical Treatment for Lumbar Degenerative Spondylolisthesis

Abstract: We enrolled 304 patients in the randomized cohort and 303 in the observational cohort. The baseline characteristics of the two cohorts were similar. The one-year crossover rates were high in the randomized cohort (approximately 40% in each direction) but moderate in the observational cohort (17% crossover to surgery and 3% crossover to nonsurgical care). The intention-to-treat analysis for the randomized cohort showed no statistically significant effects for the primary outcomes. The as-treated analysis for both cohorts combined showed a significant advantage for surgery at 3 months that increased at 1 year and diminished only slightly at 2 years. The treatment effects at 2 years were 18.1 for bodily pain (95% confidence interval [CI], 14.5 to 21.7), 18.3 for physical function (95% CI, 14.6 to 21.9), and −16.7 for the Oswestry Disability Index (95% CI, −19.5 to −13.9). There was little evidence of harm from either treatment. CONCLUSIONS In nonrandomized as-treated comparisons with careful control for potentially confounding baseline factors, patients with degenerative spondylolisthesis and spinal stenosis treated surgically showed substantially greater improvement in pain and function during a period of 2 years than patients treated nonsurgically. (ClinicalTrials. gov number, NCT00000409.)