Adequate Allocation Concealment Research Articles

Intermittent pneumatic compression for treating venous leg ulcers.

Intermittent pneumatic compression (IPC) is a mechanical method of delivering compression to swollen limbs that can be used to treat venous leg ulcers and limb swelling due to lymphoedema. To determine whether IPC increases the healing of venous leg ulcers. To determine the effects of IPC on health related quality of life of venous leg ulcer patients. In April 2014, for this third update, we searched the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We included randomised controlled trials (RCTs) that compared the effects of IPC with control (sham IPC or no IPC) or made comparisons between IPC treatment regimens, in venous ulcer management. Two review authors reviewed titles and abstracts and agreed on full studies to be retrieved. One review author extracted data and assessed studies for risk of bias and this was checked by a second review author. We identified nine randomised controlled trials (including 489 people in total). Only one trial was at low risk of bias overall having reported adequate randomisation, allocation concealment and blinded outcome assessment. In one trial (80 people) more ulcers healed with IPC than with dressings (62% vs 28%; p=0.002). Five trials compared IPC plus compression with compression alone. Two of these (97 people) found increased ulcer healing with IPC plus compression than with compression alone. The remaining three trials (122 people) found no evidence of a benefit for IPC plus compression compared with compression alone.Two trials (86 people) found no difference between IPC (without additional compression) and compression bandages alone.One trial (104 people) compared different ways of delivering IPC and found that rapid IPC healed more ulcers than slow IPC (86% vs 61%). IPC may increase healing compared with no compression. It is unclear whether it can be used instead of compression bandages. There is some limited evidence that IPC may improve healing when added to compression bandages. Rapid IPC was better than slow IPC in one trial. Further trials are required to determine the reliability of current evidence, which patients may benefit from IPC in addition to compression bandages, and the optimum treatment regimen.

Formula versus donor breast milk for feeding preterm or low birth weight infants.

When sufficient maternal breast milk is not available, alternative sources of enteral nutrition for preterm or low birth weight infants are donor breast milk or artificial formula. Donor breast milk may retain some of the non-nutritive benefits of maternal breast milk for preterm or low birth weight infants. However, feeding with artificial formula may ensure more consistent delivery of optimal levels of nutrients. Uncertainty exists about the balance of risks and benefits of feeding formula versus donor breast milk for preterm or low birth weight infants. To determine the effect of feeding with formula compared with donor breast milk on growth and development in preterm or low birth weight infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 3), MEDLINE (1966 to March 2014), EMBASE (1980 to March 2014), CINAHL (1982 to March 2014), conference proceedings and previous reviews. Randomised or quasi-randomised controlled trials comparing feeding with formula versus donor breast milk in preterm or low birth weight infants. We extracted data using the standard methods of the Cochrane Neonatal Group, with separate evaluation of trial quality and data extraction by two review authors. Nine trials, in which 1070 infants participated, fulfilled the inclusion criteria. Four trials compared standard term formula versus donor breast milk and five compared nutrient-enriched preterm formula versus donor breast milk. Only the two most recent trials used nutrient-fortified donor breast milk. The trials contain various methodological quality weaknesses, specifically uncertainty about adequate allocation concealment methods in three trials and lack of blinding in most of the trials.Formula-fed infants had higher in hospital rates of increase in weight [mean difference (MD): 2.58 (95% confidence interval (CI) 1.98 to 3.71) g/kg/day], length [MD 1.93 (95% CI 1.23 to 2.62) mm/week] and head circumference [MD 1.59 (95% CI 0.95 to 2.24) mm/week]. We did not find evidence of an effect on post-discharge growth rates or neurodevelopmental outcomes. Formula feeding increased the risk of necrotising enterocolitis: typical risk ratio 2.77 (95% CI 1.40 to 5.46); risk difference 0.04 (95% CI 0.02 to 0.07). In preterm and low birth weight infants, feeding with formula compared with donor breast milk results in a higher rate of short-term growth but also a higher risk of developing necrotising enterocolitis. Limited data on the comparison of feeding with formula versus nutrient-fortified donor breast milk are available. This limits the applicability of the findings of this review as nutrient fortification of breast milk is now a common practice in neonatal care. Future trials may compare growth, development and adverse outcomes in infants who receive formula milk versus nutrient-fortified donor breast milk given as a supplement to maternal expressed breast milk or as a sole diet.

Methodological reporting quality of randomized controlled trials in three spine journals from 2010 to 2012.

To elucidate the methodological reporting quality of randomized controlled trials (RCTs) in three spine journals from 2010 to 2012. In this study, we summarized the methodological report of RCTs in three major spine journals, including the Spine Journal, Spine and the European Spine Journal from 2010 to 2012. The methodological reporting quality, including the allocation sequence generation, allocation concealment, blinding and sample size calculation, was revealed. Number of patients, funding source, type of intervention and country were also retrieved from each trial. The methodological reporting quality was descriptively reported. Ninety trials were involved and 57.8% (52/90) reported adequate allocation sequence generation, 46.7% (42/90) reported adequate allocation concealment, 34.4% (31/90) reported adequate blinding and 37.8% (34/90) reported adequate sample size calculation. This study shows that the methodological reporting quality of RCTs in the spine field needs further improvement.

Integrating fragmented evidence by network meta-analysis: relative effectiveness of psychological interventions for adults with post-traumatic stress disorder.

To summarize the available evidence on the effectiveness of psychological interventions for patients with post-traumatic stress disorder (PTSD). We searched bibliographic databases and reference lists of relevant systematic reviews and meta-analyses for randomized controlled trials that compared specific psychological interventions for adults with PTSD symptoms either head-to-head or against control interventions using non-specific intervention components, or against wait-list control. Two investigators independently extracted the data and assessed trial characteristics. The analyses included 4190 patients in 66 trials. An initial network meta-analysis showed large effect sizes (ESs) for all specific psychological interventions (ESs between -1.10 and -1.37) and moderate effects of psychological interventions that were used to control for non-specific intervention effects (ESs -0.58 and -0.62). ES differences between various types of specific psychological interventions were absent to small (ES differences between 0.00 and 0.27). Considerable between-trial heterogeneity occurred (τ²= 0.30). Stratified analyses revealed that trials that adhered to DSM-III/IV criteria for PTSD were associated with larger ESs. However, considerable heterogeneity remained. Heterogeneity was reduced in trials with adequate concealment of allocation and in large-sized trials. We found evidence for small-study bias. Our findings show that patients with a formal diagnosis of PTSD and those with subclinical PTSD symptoms benefit from different psychological interventions. We did not identify any intervention that was consistently superior to other specific psychological interventions. However, the robustness of evidence varies considerably between different psychological interventions for PTSD, with most robust evidence for cognitive behavioral and exposure therapies.

Endoscopic release for carpal tunnel syndrome

Endoscopic release for carpal tunnel syndrome

Randomized controlled trials on complementary and traditional medicine in the korean literature.

Objective. This study aimed to identify all of the features of complementary and alternative (CAM) randomized controlled trials (RCTs) in the Korean literature and then introduce English-speaking researchers to the bibliometric and risk of bias characteristics of this literature. Methods. Eleven electronic databases and sixteen Korean journals were searched to August 2013 for RCTs of CAM therapies. Key study characteristics were extracted and risk of bias was assessed using the Cochrane Collaboration's tool for assessing risk of bias. Results. Three hundred and sixty publications met our inclusion criteria. Complementary and traditional medicine RCTs in the Korean literature emerged in the mid-1990s and increased in the mid-2000s. The most common CAM interventions include acupuncture (59.4%) and herbal medicine (8.3%). The largest proportion of trials evaluated CAM for musculoskeletal conditions (20.7%). Adequate methods of randomization were reported in 41.7% of the RCTs, whereas only 8.3% reported adequate allocation concealment. A low proportion of trials reported participant blinding (34.2%) and outcome assessor blinding (22.5%). Conclusions. Korean CAM RCTs are typically omitted from systematic reviews resulting in the potential for language bias. This study will enable these trials of diverse quality to be identified and assessed for inclusion in future systematic reviews on CAM interventions.

Are Reports of Randomized Controlled Trials Improving over Time? A Systematic Review of 284 Articles Published in High-Impact General and Specialized Medical Journals

BackgroundInadequate reporting undermines findings of randomized controlled trials (RCTs). This study assessed and compared articles published in high-impact general medical and specialized journals.MethodsReports of RCTs published in high-impact general and specialized medical journals were identified through a search of MEDLINE from January to March of 1995, 2000, 2005, and 2010. Articles that provided original data on adult patients diagnosed with chronic conditions were included in the study. Data on trial characteristics, reporting of allocation concealment, quality score, and the presence of a trial flow diagram were extracted independently by two reviewers, and discrepancies were resolved by consensus or independent adjudication. Descriptive statistics were used for quantitative variables. Comparisons between general medical and specialized journals, and trends over time were performed using Chi-square tests.ResultsReports of 284 trials were analyzed. There was a significantly higher proportion of RCTs published with adequate reporting of allocation concealment (p = 0.003), presentation of a trial flow diagram (p<0.0001) and high quality scores (p = 0.038) over time. Trials published in general medical journals had higher quality scores than those in specialized journals (p = 0.001), reported adequate allocation concealment more often (p = 0.013), and presented a trial flow diagram more often (p<0.001).InterpretationWe found significant improvements in reporting quality of RCTs published in high-impact factor journals over the last fifteen years. These improvements are likely attributed to concerted international efforts to improve reporting quality such as CONSORT. There is still much room for improvement, especially among specialized journals.

Maintenance agonist treatments for opiate-dependent pregnant women

The prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Heroin crosses the placenta and pregnant, opiate-dependent women experience a six-fold increase in maternal obstetric complications such as low birth weight, toxaemia, third trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neuro-behavioural problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome. To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions for child health status, neonatal mortality, retaining pregnant women in treatment and reducing the use of substances. We searched the Cochrane Drugs and Alcohol Group Trials Register (September 2013), PubMed (1966 to September 2013), CINAHL (1982 to September 2013), reference lists of relevant papers, sources of ongoing trials, conference proceedings and national focal points for drug research. We contacted authors of included studies and experts in the field. Randomised controlled trials assessing the efficacy of any maintenance pharmacological treatment for opiate-dependent pregnant women. We used the standard methodological procedures expected by The Cochrane Collaboration. We found four trials with 271 pregnant women. Three compared methadone with buprenorphine and one methadone with oral slow-release morphine. Three out of four studies had adequate allocation concealment and were double-blind. The major flaw in the included studies was attrition bias: three out of four had a high drop-out rate (30% to 40%) and this was unbalanced between groups.Methadone versus buprenorphine: the drop-out rate from treatment was lower in the methadone group (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.41 to 1.01, three studies, 223 participants). There was no statistically significant difference in the use of primary substance between methadone and buprenorphine (RR 1.81, 95% CI 0.70 to 4.69, two studies, 151 participants). For both, we judged the quality of evidence as low. Birth weight was higher in the buprenorphine group in the two trials that could be pooled (mean difference (MD) -365.45 g (95% CI -673.84 to -57.07), two studies, 150 participants). The third study reported that there was no statistically significant difference. For APGAR score neither of the studies which compared methadone with buprenorphine found a significant difference. For both, we judged the quality of evidence as low. Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, which is the most critical outcome, did not differ significantly between groups. We judged the quality of evidence as very low.Methadone versus slow-release morphine: there was no drop-out in either treatment group. Oral slow-release morphine seemed superior to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI 1.00 to 5.77, one study, 48 participants). We judged the quality of evidence as moderate.Only one study which compared methadone with buprenorphine reported side effects. For the mother there was no statistically significant difference; for the newborns in the buprenorphine group there were significantly fewer serious side effects.In the comparison between methadone and slow-release morphine no side effects were reported for the mother, whereas one child in the methadone group had central apnoea and one child in the morphine group had obstructive apnoea. We did not find sufficient significant differences between methadone and buprenorphine or slow-release morphineto allow us to conclude that one treatment is superior to another for all relevant outcomes. While methadone seems superior in terms of retaining patients in treatment, buprenorphine seems to lead to less severe neonatal abstinence syndrome. Additionally, even though a multi-centre, international trial with 175 pregnant women has recently been completed and its results published and included in this review, the body of evidence is still too small to draw firm conclusions about the equivalence of the treatments compared. There is still a need for randomised controlled trials of adequate sample size comparing different maintenance treatments.

2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk

Preamble and Transition to ACC/AHA Guidelines to Reduce Cardiovascular Risk S50 The goals of the American College of Cardiology (ACC) and the American Heart Association (AHA) are to prevent cardiovascular diseases (CVD); improve the management of people who have these diseases through professional education and research; and develop guidelines, standards, and policies that promote optimal patient care and cardiovascular health. Toward these objectives, the ACC and AHA have collaborated with the National Heart, Lung, and Blood Institute (NHLBI) and stakeholder and professional organizations to develop …

Reprint: 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults.

Reprint: 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults.

2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk

2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk

The impact of neutral-pH peritoneal dialysates with reduced glucose degradation products on clinical outcomes in peritoneal dialysis patients

Neutral-pH peritoneal dialysates, with reduced glucose degradation products (GDPs), have been developed to reduce peritoneal membrane damage. Here our review evaluated the impact of these solutions on clinical outcomes using data from The Cochrane CENTRAL Registry, MEDLINE, Embase, and reference lists for randomized trials of biocompatible solutions. Summary estimates of effect were obtained using a random-effects model of 20 eligible trials encompassing 1383 patients. The quality of studies was generally poor, such that 13 studies had greater than a 20% loss to follow-up and only 3 trials reported adequate concealment of allocation. Use of neutral-pH dialysates with reduced GDPs resulted in larger urine volumes (7 trials; 520 patients; mean difference 126 ml/day, 95% CI 27-226), improved residual renal function after 12 months (6 trials; 360 patients; standardized mean difference 0.31, 95% confidence interval 0.10-0.52), and a trend to reduced inflow pain (1 trial; 58 patients; relative risk 0.51, 95% CI 0.24-1.08). However, there was no significant effect on body weight, hospitalization, peritoneal solute transport rate, peritoneal small-solute clearance, peritonitis, technique failure, patient survival, or adverse events. No significant harms were identified. Thus, based on generally poor quality trials, the use of neutral-pH peritoneal dialysates with reduced GDPs resulted in greater urine volumes and residual renal function after 12 months, but without other clinical benefits. Larger, better-quality studies are needed for accurate evaluation of the impact of these newer dialysates on patient-level hard outcomes.

Exercise for depression

Depression is a common and important cause of morbidity and mortality worldwide. Depression is commonly treated with antidepressants and/or psychological therapy, but some people may prefer alternative approaches such as exercise. There are a number of theoretical reasons why exercise may improve depression. This is an update of an earlier review first published in 2009. To determine the effectiveness of exercise in the treatment of depression in adults compared with no treatment or a comparator intervention. We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Controlled Trials Register (CCDANCTR) to 13 July 2012. This register includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years); MEDLINE (1950 to date); EMBASE (1974 to date) and PsycINFO (1967 to date). We also searched www.controlled-trials.com, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. No date or language restrictions were applied to the search.We conducted an additional search of the CCDANCTR up to 1st March 2013 and any potentially eligible trials not already included are listed as 'awaiting classification.' Randomised controlled trials in which exercise (defined according to American College of Sports Medicine criteria) was compared to standard treatment, no treatment or a placebo treatment, pharmacological treatment, psychological treatment or other active treatment in adults (aged 18 and over) with depression, as defined by trial authors. We included cluster trials and those that randomised individuals. We excluded trials of postnatal depression. Two review authors extracted data on primary and secondary outcomes at the end of the trial and end of follow-up (if available). We calculated effect sizes for each trial using Hedges' g method and a standardised mean difference (SMD) for the overall pooled effect, using a random-effects model risk ratio for dichotomous data. Where trials used a number of different tools to assess depression, we included the main outcome measure only in the meta-analysis. Where trials provided several 'doses' of exercise, we used data from the biggest 'dose' of exercise, and performed sensitivity analyses using the lower 'dose'. We performed subgroup analyses to explore the influence of method of diagnosis of depression (diagnostic interview or cut-off point on scale), intensity of exercise and the number of sessions of exercise on effect sizes. Two authors performed the 'Risk of bias' assessments. Our sensitivity analyses explored the influence of study quality on outcome. Thirty-nine trials (2326 participants) fulfilled our inclusion criteria, of which 37 provided data for meta-analyses. There were multiple sources of bias in many of the trials; randomisation was adequately concealed in 14 studies, 15 used intention-to-treat analyses and 12 used blinded outcome assessors.For the 35 trials (1356 participants) comparing exercise with no treatment or a control intervention, the pooled SMD for the primary outcome of depression at the end of treatment was -0.62 (95% confidence interval (CI) -0.81 to -0.42), indicating a moderate clinical effect.There was moderate heterogeneity (I² = 63%).When we included only the six trials (464 participants) with adequate allocation concealment, intention-to-treat analysis and blinded outcome assessment, the pooled SMD for this outcome was not statistically significant (-0.18, 95% CI -0.47 to 0.11). Pooled data from the eight trials (377 participants) providing long-term follow-up data on mood found a small effect in favour of exercise (SMD -0.33, 95% CI -0.63 to -0.03).Twenty-nine trials reported acceptability of treatment, three trials reported quality of life, none reported cost, and six reported adverse events.For acceptability of treatment (assessed by number of drop-outs during the intervention), the risk ratio was 1.00 (95% CI 0.97 to 1.04).Seven trials compared exercise with psychological therapy (189 participants), and found no significant difference (SMD -0.03, 95% CI -0.32 to 0.26).Four trials (n = 300) compared exercise with pharmacological treatment and found no significant difference (SMD -0.11, -0.34, 0.12). One trial (n = 18) reported that exercise was more effective than bright light therapy (MD -6.40, 95% CI -10.20 to -2.60).For each trial that was included, two authors independently assessed for sources of bias in accordance with the Cochrane Collaboration 'Risk of bias' tool.In exercise trials, there are inherent difficulties in blinding both those receiving the intervention and those delivering the intervention.Many trials used participant self-report rating scales as a method for post-intervention analysis, which also has the potential to bias findings. Exercise is moderately more effective than a control intervention for reducing symptoms of depression, but analysis of methodologically robust trials only shows a smaller effect in favour of exercise. When compared to psychological or pharmacological therapies, exercise appears to be no more effective, though this conclusion is based on a few small trials.

Music to Reduce Pain and Distress in the Pediatric Emergency Department

Many medical procedures aimed at helping children cause them pain and distress, which can have long-lasting negative effects. Music is a form of distraction that may alleviate some of the pain and distress experienced by children while undergoing medical procedures. To compare music with standard care to manage pain and distress. Randomized clinical trial conducted in a pediatric emergency department with appropriate sequence generation and adequate allocation concealment from January 1, 2009, to March 31, 2010. Individuals assessing the primary outcome were blind to treatment allocation. A total of 42 children aged 3 to 11 years undergoing intravenous placement were included. Music (recordings selected by a music therapist via ambient speakers) vs standard care. The primary outcome was behavioral distress assessed blinded using the Observational Scale of Behavioral Distress-Revised. The secondary outcomes included child-reported pain, heart rate, parent and health care provider satisfaction, ease of performing the procedure, and parental anxiety. With or without controlling for potential confounders, we found no significant difference in the change in behavioral distress from before the procedure to immediately after the procedure. When children who had no distress during the procedure were removed from the analysis, there was a significantly less increase in distress for the music group (standard care group = 2.2 vs music group = 1.1, P < .05). Pain scores among children in the standard care group increased by 2 points, while they remained the same in the music group (P = .04); the difference was considered clinically important. The pattern of parent satisfaction with the management of children's pain was different between groups, although not statistically significant (P = .07). Health care providers reported that it was easier to perform the procedure for children in the music group (76% very easy) vs the standard care group (38% very easy) (P = .03). Health care providers were more satisfied with the intravenous placement in the music group (86% very satisfied) compared with the standard care group (48%) (P = .02). Music may have a positive impact on pain and distress for children undergoing intravenous placement. Benefits were also observed for the parents and health care providers. clinicaltrials.gov Identifier: NCT00761033.

10-year trend in quantity and quality of pediatric randomized controlled trials published in mainland China: 2002–2011

BackgroundQuality assessment of pediatric randomized controlled trials (RCTs) in China is limited. The aim of this study was to evaluate the quantitative trends and quality indicators of RCTs published in mainland China over a recent 10-year period.MethodsWe individually searched all 17 available pediatric journals published in China from January 1, 2002 to December 30, 2011 to identify RCTs of drug treatment in participants under the age of 18 years. The quality was evaluated according to the Cochrane quality assessment protocol.ResultsOf 1287 journal issues containing 44398 articles, a total of 2.4% (1077/44398) articles were included in the analysis. The proportion of RCTs increased from 0.28% in 2002 to 0.32% in 2011. Individual sample sizes ranged from 10 to 905 participants (median 81 participants); 2.3% of the RCTs were multiple center trials; 63.9% evaluated Western medicine, 32.5% evaluated traditional Chinese medicine; 15% used an adequate method of random sequence generation; and 10.4% used a quasi-random method for randomization. Only 1% of the RCTs reported adequate allocation concealment and 0.6% reported the method of blinding. The follow-up period was from 7 days to 96 months, with a median of 7.5 months. There was incomplete outcome data reported in 8.3%, of which 4.5% (4/89) used intention-to-treat analysis. Only 0.4% of the included trials used adequate random sequence allocation, concealment and blinding. The articles published from 2007 to 2011 revealed an improvement in the randomization method compared with articles published from 2002 to 2006 (from 2.7% to 23.6%, p = 0.000).ConclusionsIn mainland China, the quantity of RCTs did not increase in the pediatric population, and the general quality was relatively poor. Quality improvements were suboptimal in the later 5 years.

Trends in Worldwide Volume and Methodological Quality of Surgical Randomized Controlled Trials

To assess worldwide trends in volume and methodological quality of published surgical randomized controlled trials (RCTs) over the past decade. Randomized controlled trials are essential for clinical decision making. It has repeatedly been suggested that surgical RCTs are scarce and of mediocre quality. We systematically searched PubMed for surgical RCTs published in 1999 and 2009. Characteristics and risks of bias were extracted. Trials where compared between study years and geographical regions. Primary outcome was "low risk of bias," defined by all of the following: adequate allocation generation and concealment, intention-to-treat analysis, and adequate dropout handling. The volume of published surgical RCTs increased by 50%, from 300 in 1999 to 450 in 2009. Volume increased in Europe (27% increase), Asia/Oceania (160% increase), and Africa/South America (416% increase) but decreased in North America (23% decrease), although the United States remained the country with the highest number of published RCTs. In 2009, methodological quality of surgical trials improved in terms of sample size calculation, adequate generation of randomization sequence, concealment of randomization sequence, and use of intention-to-treat analysis as compared with 1999 (P < 0.001 for all). The proportion of low risk of bias trials increased from 6% to 14% (prevalence ratio 2.59; 95% confidence interval 1.55-4.32). In 2009, the highest proportion of low risk of bias trials was from Europe (23%), whereas the lowest was from Asia/Oceania (5%). Volume and quality of surgical RCTs improved although striking differences exist between continents and countries. Structured education in trial methodology, enforced adherence to existing guidelines, and improved research infrastructure may guide further improvements.

Systematic review evaluating cardiovascular events of the 5-alpha reductase inhibitor - Dutasteride

A recently published large, long-term randomized controlled trial (RCT) brought into question the safety of dutasteride after a significantly increased risk of 'cardiac failure' was noted in the dutasteride arm of the trial compared with placebo. Our objective was to perform a meta-analysis to assess the risk of cardiovascular adverse events with the use of dutasteride for the prevention or treatment of prostatic disease. We searched MEDLINE and EMBASE, unpublished articles identified through FDA/EMEA websites, study registers of pharmaceutical companies and reference lists of articles. Parallel-group, randomized controlled trials where men received dutasteride for the prevention of prostate cancer or treatment of prostatic hyperplasia against any comparator intervention were included. Heart failure was the primary outcome of interest but we also looked at myocardial infarction and stroke. Fixed-effect meta-analysis of pooled relative risk (RR) ratios of adverse effect outcomes was conducted. In all, 12 RCTs were included in the meta-analysis after detailed screening of 564 citations. The total number of participants was 18,802, and study duration ranged from 6 to 208 weeks. Only two trials provided details on adequate allocation concealment, whereas all the trials stated they were double blind in nature. Dutasteride was not associated with a statistically significant increased risk of heart failure (RR 1·05; 95% confidence interval [CI], 0·71-1·57, I(2) = 20%), myocardial infarction (RR 1·00; 95% CI 0·77-1·30, I(2) = 0%) and stroke (RR, 1·20; 95% CI 0·88-1·64, I(2) = 0%) as compared to controls. We did not find consistent evidence of a significant association between dutasteride therapy and the risk of cardiovascular adverse events.

Cognitive rehabilitation for spatial neglect following stroke

Unilateral spatial neglect causes difficulty attending to one side of space. Various rehabilitation interventions have been used but evidence of their benefit is lacking. To assess whether cognitive rehabilitation improves functional independence, neglect (as measured using standardised assessments), destination on discharge, falls, balance, depression/anxiety and quality of life in stroke patients with neglect measured immediately post-intervention and at longer-term follow-up; and to determine which types of interventions are effective and whether cognitive rehabilitation is more effective than standard care or an attention control. We searched the Cochrane Stroke Group Trials Register (last searched June 2012), MEDLINE (1966 to June 2011), EMBASE (1980 to June 2011), CINAHL (1983 to June 2011), PsycINFO (1974 to June 2011), UK National Research Register (June 2011). We handsearched relevant journals (up to 1998), screened reference lists, and tracked citations using SCISEARCH. We included randomised controlled trials (RCTs) of cognitive rehabilitation specifically aimed at spatial neglect. We excluded studies of general stroke rehabilitation and studies with mixed participant groups, unless more than 75% of their sample were stroke patients or separate stroke data were available. Two review authors independently selected studies, extracted data, and assessed study quality. For subgroup analyses, review authors independently categorised the approach underlying the cognitive intervention as either 'top-down' (interventions that encourage awareness of the disability and potential compensatory strategies) or 'bottom-up' (interventions directed at the impairment but not requiring awareness or behavioural change, e.g. wearing prisms or patches). We included 23 RCTs with 628 participants (adding 11 new RCTs involving 322 new participants for this update). Only 11 studies were assessed to have adequate allocation concealment, and only four studies to have a low risk of bias in all categories assessed. Most studies measured outcomes using standardised neglect assessments: 15 studies measured effect on activities of daily living (ADL) immediately after the end of the intervention period, but only six reported persisting effects on ADL. One study (30 participants) reported discharge destination and one study (eight participants) reported the number of falls.Eighteen of the 23 included RCTs compared cognitive rehabilitation with any control intervention (placebo, attention or no treatment). Meta-analyses demonstrated no statistically significant effect of cognitive rehabilitation, compared with control, for persisting effects on either ADL (five studies, 143 participants) or standardised neglect assessments (eight studies, 172 participants), or for immediate effects on ADL (10 studies, 343 participants). In contrast, we found a statistically significant effect in favour of cognitive rehabilitation compared with control, for immediate effects on standardised neglect assessments (16 studies, 437 participants, standardised mean difference (SMD) 0.35, 95% confidence interval (CI) 0.09 to 0.62). However, sensitivity analyses including only studies of high methodological quality removed evidence of a significant effect of cognitive rehabilitation.Additionally, five of the 23 included RCTs compared one cognitive rehabilitation intervention with another. These included three studies comparing a visual scanning intervention with another cognitive rehabilitation intervention, and two studies (three comparison groups) comparing a visual scanning intervention plus another cognitive rehabilitation intervention with a visual scanning intervention alone. Only two small studies reported a measure of functional disability and there was considerable heterogeneity within these subgroups (I² > 40%) when we pooled standardised neglect assessment data, limiting the ability to draw generalised conclusions.Subgroup analyses exploring the effect of having an attention control demonstrated some evidence of a statistically significant difference between those comparing rehabilitation with attention control and those with another control or no treatment group, for immediate effects on standardised neglect assessments (test for subgroup differences, P = 0.04). The effectiveness of cognitive rehabilitation interventions for reducing the disabling effects of neglect and increasing independence remains unproven. As a consequence, no rehabilitation approach can be supported or refuted based on current evidence from RCTs. However, there is some very limited evidence that cognitive rehabilitation may have an immediate beneficial effect on tests of neglect. This emerging evidence justifies further clinical trials of cognitive rehabilitation for neglect. However, future studies need to have appropriate high quality methodological design and reporting, to examine persisting effects of treatment and to include an attention control comparator.

Antibiotics for community-acquired pneumonia in children.

Pneumonia caused by bacterial pathogens is the leading cause of mortality in children in low-income countries. Early administration of antibiotics improves outcomes. To identify effective antibiotic drug therapies for community-acquired pneumonia (CAP) of varying severity in children by comparing various antibiotics. We searched CENTRAL 2012, Issue 10; MEDLINE (1966 to October week 4, 2012); EMBASE (1990 to November 2012); CINAHL (2009 to November 2012); Web of Science (2009 to November 2012) and LILACS (2009 to November 2012). Randomised controlled trials (RCTs) in children of either sex, comparing at least two antibiotics for CAP within hospital or ambulatory (outpatient) settings. Two review authors independently extracted data from the full articles of selected studies. We included 29 trials, which enrolled 14,188 children, comparing multiple antibiotics. None compared antibiotics with placebo.Assessment of quality of study revealed that 5 out of 29 studies were double-blind and allocation concealment was adequate. Another 12 studies were unblinded but had adequate allocation concealment, classifying them as good quality studies. There was more than one study comparing co-trimoxazole with amoxycillin, oral amoxycillin with injectable penicillin/ampicillin and chloramphenicol with ampicillin/penicillin and studies were of good quality, suggesting the evidence for these comparisons was of high quality compared to other comparisons.In ambulatory settings, for treatment of World Health Organization (WHO) defined non-severe CAP, amoxycillin compared with co-trimoxazole had similar failure rates (odds ratio (OR) 1.18, 95% confidence interval (CI) 0.91 to 1.51) and cure rates (OR 1.03, 95% CI 0.56 to 1.89). Three studies involved 3952 children.In children with severe pneumonia without hypoxaemia, oral antibiotics (amoxycillin/co-trimoxazole) compared with injectable penicillin had similar failure rates (OR 0.84, 95% CI 0.56 to 1.24), hospitalisation rates (OR 1.13, 95% CI 0.38 to 3.34) and relapse rates (OR 1.28, 95% CI 0.34 to 4.82). Six studies involved 4331 children below 18 years of age.In very severe CAP, death rates were higher in children receiving chloramphenicol compared to those receiving penicillin/ampicillin plus gentamicin (OR 1.25, 95% CI 0.76 to 2.07). One study involved 1116 children. For treatment of patients with CAP in ambulatory settings, amoxycillin is an alternative to co-trimoxazole. With limited data on other antibiotics, co-amoxyclavulanic acid and cefpodoxime may be alternative second-line drugs. Children with severe pneumonia without hypoxaemia can be treated with oral amoxycillin in an ambulatory setting. For children hospitalised with severe and very severe CAP, penicillin/ampicillin plus gentamycin is superior to chloramphenicol. The other alternative drugs for such patients are co-amoxyclavulanic acid and cefuroxime. Until more studies are available, these can be used as second-line therapies.There is a need for more studies with radiographically confirmed pneumonia in larger patient populations and similar methodologies to compare newer antibiotics. Recommendations in this review are applicable to countries with high case fatalities due to pneumonia in children without underlying morbidities and where point of care tests for identification of aetiological agents for pneumonia are not available.

Acute Traumatic Brain Injury: Is Current Management Evidence Based? An Empirical Analysis of Systematic Reviews

Traumatic brain injury (TBI) is a major health and socioeconomic problem worldwide with a high rate of death and long-term disability. Previous studies have summarized evidence from large-scale randomized trials, finding no intervention showing convincing efficacy for acute TBI management. The present empirical study set out to assess another crucial component of evidence base-systematic review, which contributes a lot to evidence-based health care, in terms of clinical issues, methodological aspects, and implication for practice and research. A total of 44 systematic reviews pertaining to therapeutic interventions for acute TBI were identified through electronic database searching, clinical guideline retrieval, and expert consultation, of which 21 were published in Cochrane Library and 23 in peer-reviewed journals. Their methodological quality was generally satisfactory, with the median Overview Quality Assessment Questionnaire score of 5.5 (interquartile range 2-7). Cochrane reviews are of better quality than regular journal reviews. Twenty-nine high-quality reviews provided no conclusive evidence for the investigated 22 interventions except for an adverse effect of corticosteroids. Less than one-third of the component trials were reported with adequate allocation concealment. Additionally other methodological flaws in design-for example, ignoring heterogeneity among the TBI population-also contributed to the failure of past clinical research. Based on the above findings, evidence from both systematic reviews and clinical trials does not fully support current management of acute TBI. Translating from laboratory success to clinical effect remains an unique challenge. Accordingly it may be the time to rethink the way in future practice and clinical research in TBI.