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The quality of reporting of health economic evaluations for rehabilitation services has been questioned, limiting the ability to provide accurate recommendations for health decisions.To document current overall reporting quality of the published literature for economic evaluations of rehabilitation services using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), and to identify factors that could influence the quality of reporting.Electronic literature searches were performed using MEDLINE and the NHS Economic Evaluations DatabaseProspective rehabilitation economic evaluation articles from 2013 to 2020 were selected.Data were extracted by one reviewer and independently verified by a second reviewer.Title and abstracts of 3,454 papers were reviewed. 204 papers were selected for a full text screening. From those, 129 potential papers were identified to be included in this study.Only two databases were used in data collection, and papers were selected from 2013 to 2020 only.Inconsistent reporting in health economic evaluations of rehabilitation services has continued, despite the availability of the CHEERS checklist. The methods of the analyzed studies were frequently under-reported, thereby creating challenges in determining whether the results reported were valid.IMPLICATIONS FOR REHABILITATIONVariable quality of reporting has been identified in rehabilitation research assessing cost-effectiveness.To grow as an area of expertise, the field of rehabilitation must produce research demonstrating its cost-effectiveness.Both rehabilitation clinicians and funders would benefit from full and transparent information to identify optimal solutions for effective and efficient care.

BACKGROUND: Prior meta-analyses measuring thiazide-induced glycemic change have demonstrated an increased risk of incident diabetes; however, this measure’s definition has changed over time. AIM: To determine the magnitude of change in fasting plasma glucose (FPG) for thiazide diuretics. DATA SOURCES: A research librarian designed and conducted searches in Medline®, EMBASE, and EBM Reviews-Cochrane Central Register of Controlled Trials (inception through July 2018) and International Pharmaceutical Abstracts (inception to December 2014). STUDY SELECTION: Randomized, controlled trials comparing a thiazide or thiazide-like diuretic to any comparator reporting FPG were identified. Trials enrolling

Objective To identify, synthesize, and categorize the methodological issues faced by the rehabilitation field. Data Sources A scoping review was conducted using studies identified in MEDLINE, the Cochrane Library, EMBASE, Web of Science, Scopus, Physiotherapy Evidence Database, and Google Scholar up to August 2018. Study Selection We included all type of publications describing methodological issues in rehabilitation research where rehabilitation is described as a multimodal process. The methodological issues have been categorized and classified. Data Extraction The synthesis included qualitative and quantitative analysis. To focus the attention on rehabilitation, we post hoc divided in “specific issues” (highly related to, even if not exclusive of, rehabilitation research) and “generic issues” (common in biomedical research). Data Synthesis Seventy-one publications were included: 68% were narrative reviews, 15% systematic reviews, 7% editorials, 4% meta-epidemiologic studies, and 5% others. Specific methodological issues include the following: problematic application of randomized controlled trials (32%), absent definition of core outcome sets (28%), poor interventions description (22%), weak methodological (conducting) and reporting quality (21%), scarce clinical practice applicability (14%), lack of blinding assessor (10%), inadequate randomization methods or inadequate allocation concealment (8%), and inadequate participants description and recruitment (8%). “Generic” issues included the following: data and statistical description (31%), authors’ methodological training (7%), peer review process (6%, n=4), funding declaration (6%), ethical statement (3%), protocol registration (3%), and conflict of interest declaration (1%). Conclusions Methodological and reporting issues might influence the quality of the evidence produced in rehabilitation research. The next steps to move forward in the field of rehabilitation could be to evaluate the influence of all these issues on the validity of trial results through meta-epidemiologic studies and to develop specific checklists to provide guidance to authors to improve the reporting and conduct of trials in this field.

Sleep health is an important aspect of wellbeing and merits incorporation into workplace health promotion programs for employees. Men are a unique population with whom many traditional workplace health promotion programs have had limited success. This systematic review posed the question do workplace health promotion programs improve sleep among men, and what program design features contribute to improving sleep among working men? Databases searched were MEDLINE, EMBASE, the Cochrane Library, CINHAL, Academic Search Complete and Health Source: Nursing/Academic Edition and Google Scholar. Empirical research reporting non-pharmacological behavioral sleep programs and/or interventions for working men were eligible for review. 1049 articles were identified; 15 intervention studies were included: 13 interventions were delivered through workplaces, and two recruited workers to programs delivered outside of work. Interventions incorporated health education, stress reduction/relaxation, and/or physical activity components. Eleven studies reported positive findings for sleep health outcome(s) in men. A moderate level of evidence exists for sleep health programs with physical activity and stress management components. Evidence for the effectiveness of sleep health education programs was mixed. That only one study included a gender-sensitized intervention, where men's preferences shaped the content of a stress-reduction program which resulted in improved sleep quality, attests to the insufficient evidence and lack of gender-specific content and analyses. Next research steps should include considering cultural constructions of masculinity in program design in order to strengthen the appeal and engagement of men, and optimize health benefits for working men.

Background and Objectives In long-term care (LTC) facilities, nursing staff are important contributors to resident care and well-being. Despite this, the relationships between nursing staff coverage, care hours, and quality of resident care in LTC facilities are not well understood and have implications for policy-makers. This systematic review summarizes current evidence on the relationship between nursing staff coverage, care hours, and quality of resident care in LTC facilities. Research Design and Methods A structured literature search was conducted using four bibliographic databases and gray literature sources. Abstracts were screened by two independent reviewers using Covidence software. Data from the included studies were summarized using a pretested extraction form. The studies were critically appraised, and their results were synthesized narratively. Results The systematic searched yielded 15,842 citations, of which 54 studies (all observational) were included for synthesis. Most studies (n = 53, 98%) investigated the effect of nursing staff time on resident care. Eleven studies addressed minimum care hours and quality of care. One study examined the association between different nursing staff coverage models and resident outcomes. Overall, the quality of the included studies was poor. Discussion and Implications Because the evidence was inconsistent and of low quality, there is uncertainty about the direction and magnitude of the association between nursing staff time and type of coverage on quality of care. More rigorously designed studies are needed to test the effects of different cutoffs of care hours and different nursing coverage models on the quality of resident care in LTC facilities.

Background— There is an ongoing controversy regarding the safety and effectiveness of metformin in the setting of heart failure (HF). Therefore, we undertook a systematic review of the trial and nontrial evidence for metformin in patients with diabetes mellitus and HF. Methods and Results— We conducted a comprehensive search for controlled studies, evaluating the association between metformin and morbidity and mortality in people with diabetes mellitus and HF. Two reviewers independently identified citations, extracted data, and evaluated quality. Risk estimates were abstracted and pooled where appropriate. As measures of overall safety, we examined all-cause mortality and all-cause hospitalizations. Nine cohort studies were included; no randomized controlled trials were identified. Most (5 of 9) studies were published in 2010 and were of good quality. Metformin was associated with reduced mortality compared with controls (mostly sulfonylurea therapy): 23% versus 37% (pooled adjusted risk estimates: 0.80; 0.74–0.87; I 2 =15%; P I 2 =0%; P =0.34), nor in those with HF and chronic kidney disease (pooled adjusted risk estimate: 0.81; 0.64–1.02; P =0.08). Metformin was associated with a small reduction in all-cause hospitalizations (pooled adjusted risk estimate: 0.93; 0.89–0.98; I 2 =0%; P =0.01). Metformin was not associated with increased risk of lactic acidosis. Conclusions— The totality of evidence indicates that metformin is at least as safe as other glucose-lowering treatments in patients with diabetes mellitus and HF and even in those with reduced left ventricular ejection fraction or concomitant chronic kidney disease. Until trial data become available, metformin should be considered the treatment of choice for patients with diabetes mellitus and HF.

BACKGROUND: Pharmaceutical industry-sponsored research has been shown to be biased toward reporting positive results. Frequent industry participation in trials assessing the efficacy of inhaled corticosteroid (ICS) and long-acting beta2-agonist (LABA) combination treatment makes assessing industry influence difficult and warrants an assessment of specific potential publication bias in this area.OBJECTIVE: To describe the frequency of industry involvement in ICS/LABA trials and explore associations among significant outcomes, type of industry involvement and type of primary outcome.METHODS: A systematic review of trials comparing ICS/LABA combination therapy with ICS monotherapy for asthma was conducted. Data concerning the type of industry sponsorship, primary outcome and statistical results were collected. Comparisons between type of sponsorship and significant results were analyzed using Pearson’s χ2test and relative risk.RESULTS: Of 91 included studies (median year of publication 2005 [interquartile range 1994 to 2008]), 86 (95%) reported pharmaceutical involvement. Author affiliation was reported in 49 of 86 (57%), and 19 of 86 (22%) were industry-reported trials without full publications. The remainder were published journal articles. Studies with a first or senior author affiliated with industry were 1.5 times more likely to report statistically significant results for the primary outcome compared with studies with other types of industry involvement. Pulmonary measures were 1.5 times more likely to be statistically significant than were measures of asthma control.CONCLUSIONS: The potential biases identified were consistent with other research focused on author role and industry involvement, and suggest that degree of bias may vary with type of affiliation.

CONTEXT: Alcohol and other drug (AOD) misuse by youth is a significant public health concern. Unanticipated treatment for AOD-related morbidities is often sought in hospital emergency departments (EDs). Screening instruments that rapidly identify patients who require further diagnostic evaluation and/or brief intervention are critically important. OBJECTIVE: To summarize evidence on screening instruments that can assist emergency care clinicians in identifying AOD misuse in pediatric patients. METHODS: Fourteen electronic databases (including Medline, Embase, and PsycINFO) and reference screening were used. Psychometric and prospective diagnostic studies were selected if the instrument focused on detecting AOD misuse in patients aged 21 years or younger in the ED. Two reviewers independently assessed quality and extracted data. Validity and reliability data were collected for psychometric studies. Instrument performance was assessed by using sensitivity, specificity, and positive (LR+) and negative (LR−) likelihood ratios. Meta-analysis was not possible because of clinical and measurement heterogeneity. RESULTS: Of the 1545 references initially identified, 6 studies met inclusion criteria; these studies evaluated 11 instruments for universal or targeted screening of alcohol misuse. Instruments based on diagnostic criteria for AOD disorders were effective in detecting alcohol abuse and dependence (sensitivity: 0.88; specificity: 0.90; LR+: 8.80) and cannabis use disorder (sensitivity: 0.96; specificity: 0.86; LR+: 6.83). CONCLUSIONS: On the basis of the current evidence, we recommend that emergency care clinicians use a 2-question instrument for detecting youth alcohol misuse and a 1-question instrument for detecting cannabis misuse. Additional research is required to definitively answer whether these tools should be used as targeted or universal screening approaches in the ED.

Objective This study assessed the impact of systematic review and data extraction experience on the accuracy and efficiency of data extraction in systematic reviews. Study Design and Setting We conducted a prospective cross-sectional study from October to December 2006. Participants were classified as having minimal, moderate, or substantial experience in systematic reviews and data extraction. Three studies on insomnia treatment were extracted. Our primary outcome was the accuracy of data extraction. Data sets of each experience level were analyzed for errors in data extraction and results of meta-analyses. Additionally, the time required for completion of data extraction was compared. Results Error rates were similar across the various levels of experience and ranged from 28.3% to 31.2%. Mean rates for errors of omission (11.3–16.4%) were generally lower than those for errors of inaccuracy (13.9–17.9%). There were no significant differences in error rates or accuracy of meta-analysis results between groups. Time required approached significance, with minimally experienced participants requiring the most time. Conclusion Overall, there were high error rates by participants at all experience levels; however, time required for extraction tended to decrease with experience. These results illustrate the need to develop strategies aimed at mastery of data extraction, rather than reliance on previous data extraction experience alone.

Objective: To conduct a systematic review of the efficacy of music for medical indications in term or preterm neonates. Methods: We searched 17 electronic databases, subject bibliographies, reference lists and trials registries. Two reviewers independently screened studies for inclusion, assessed methodological quality, and extracted data. Meta-analysis was not feasible due to heterogeneity in outcomes so a qualitative analysis is presented. Results: Nine randomised trials were included. The methodological quality was generally poor (median Jadad score = 1). The outcomes most commonly reported were physiological measures (heart rate (HR), respiratory rate, oxygen saturation (Sao 2 )), behavioural state and pain. Six studies evaluated music for the painful procedures circumcision (three trials) and heel prick (three trials). For circumcisions, one high quality pilot study (n = 23) showed benefits of music for the outcomes of HR, Sao 2 and pain, while two low quality studies showed no difference. For heel prick, three low quality studies provided some evidence that music may be beneficial primarily for measures of behaviour and pain. The remaining studies evaluated the use of music in preterm infants to improve physiological and behavioural parameters (n = 31; benefits observed for behavioural parameters), to reinforce non-nutritive sucking via use of a pacifier activated lullaby (n = 32; significant increase in feeding rates), and to influence physiological stability and behaviours in infants with chronic lung disease (n = 22; no significant differences for outcomes assessed). Conclusions: The heterogeneity in study populations, interventions and outcomes precludes definitive conclusions around efficacy. There is preliminary evidence for some therapeutic benefits of music for specific indications; however, these findings need to be confirmed in methodologically rigorous trials.

Objective To determine the sensitivity and precision of existing search strategies for retrieving child health systematic reviews in MEDLINE using PubMed. Design Filter (diagnostic) accuracy study. We identified existing search strategies for systematic reviews, combined them with a filter that identifies articles relevant to child health, and applied the combination in MEDLINE to a reference set of child health systematic reviews. Main Outcome Measures Total number of records retrieved, sensitivity, and precision. Results We tested 9 search filters. Sensitivity of the systematic review filters combined with the child filter ranged from 68% to 96%; sensitivity of the child filter alone was 98%. The number of records retrieved with PubMed (limited to January 1990-January 2006) by the systematic review filters combined with the child filter ranged from 7861 to 618 053. Precision for the combined filters ranged from 2% to 52%. Because of poor reporting of specific systematic review criteria in both titles and abstracts, in 25% of the records screened we were unsure whether the article concerned a systematic review according to our definition. Conclusions The high numbers of records yielded by sensitive search strategies and the low precision threaten the use of systematic reviews for clinical decision making and guideline development. Reporting of specific systematic review criteria in titles and abstracts is poor, and reporting recommendations given by Quality of Reporting of Meta-analyses (QUOROM) should be used more strictly. To make identification using MEDLINE easier, there is an urgent need to set minimal criteria that any review should fulfill for it to be indexed as a systematic review.

Background and Objective To conduct a pilot study to compare the frequency of errors that accompany single vs. double data extraction, compare the estimate of treatment effect derived from these methods, and compare the time requirements for these methods. Methods Reviewers were randomized to the role of data extractor or data verifier, and were blind to the study hypothesis. The frequency of errors associated with each method of data extraction was compared using the McNemar test. The data set for each method was used to calculate an efficacy estimate by each method, using standard meta-analytic techniques. The time requirement for each method was compared using a paired t-test. Results Single data extraction resulted in more errors than double data extraction (relative difference: 21.7%, P = .019). There was no substantial difference between methods in effect estimates for most outcomes. The average time spent for single data extraction was less than the average time for double data extraction (relative difference: 36.1%, P = .003). Conclusion In the case that single data extraction is used in systematic reviews, reviewers and readers need to be mindful of the possibility for more errors and the potential impact these errors may have on effect estimates.

Background Rural residents face numerous barriers to healthcare access and studies suggest poorer health outcomes for rural patients. Therefore we undertook a systematic review to determine if cardiovascular medication utilization and adherence patterns differ for rural versus urban patients. Methods A comprehensive search of major electronic datasets was undertaken for controlled clinical trials and observational studies comparing utilization or adherence to cardiovascular medications in rural versus urban adults with cardiovascular disease or diabetes. Two reviewers independently identified citations, extracted data, and evaluated quality using the STROBE checklist. Risk estimates were abstracted and pooled where appropriate using random effects models. Methods and reporting were in accordance with MOOSE guidelines. Results Fifty-one studies were included of fair to good quality (median STROBE score 17.5). Although pooled unadjusted analyses suggested that patients in rural areas were less likely to receive evidence-based cardiovascular medications (23 studies, OR 0.88, 95% CI 0.79, 0.98), pooled data from 21 studies adjusted for potential confounders indicated no rural–urban differences (adjusted OR 1.02, 95% CI 0.91, 1.13). The high heterogeneity observed (I2 = 97%) was partially explained by treatment setting (hospital, ambulatory care, or community-based sample), age, and disease. Adherence did not differ between urban versus rural patients (3 studies, OR 0.94, 95% CI 0.39, 2.27, I2 = 91%). Conclusions We found no consistent differences in rates of cardiovascular medication utilization or adherence among adults with cardiovascular disease or diabetes living in rural versus urban settings. Higher quality evidence is needed to determine if differences truly exist between urban and rural patients in the use of, and adherence to, evidence-based medications.

Some studies suggest better outcomes with macrolide therapy for critically ill patients with community-acquired pneumonia. To further explore this, we performed a systematic review of studies with mortality endpoints that compared macrolide therapy with other regimens in critically ill patients with community-acquired pneumonia.Studies were identified via electronic databases, grey literature, and conference proceedings through May 2013.Using prespecified criteria, two reviewers selected studies; studies of outpatients and hospitalized noncritically ill patients were excluded.Two reviewers extracted data and evaluated bias using the Newcastle-Ottawa Scale. Random effects models were used to generate pooled risk ratios and evaluate heterogeneity (I).Twenty-eight observational studies (no randomized control trials) were included. Average age ranged from 58 to 78 years and 14-49% were women. In our primary analysis of 9,850 patients, macrolide use was associated with statistically significant lower mortality compared with nonmacrolides (21% [846 of 4,036 patients] vs 24% [1,369 of 5,814]; risk ratio, 0.82; 95% CI, 0.70-0.97; p = 0.02; I = 63%). When macrolide monotherapy was excluded, the macrolide mortality benefit was maintained (21% [737 of 3,447 patients] vs 23% [1,245 of 5,425]; risk ratio, 0.84; 95% CI, 0.71-1.00; p = 0.05; I = 60%). When broadly guideline-concordant regimens were compared, there was a trend to improved mortality and heterogeneity was reduced (20% [511 of 2,561 patients] mortality with beta-lactam/macrolide therapy vs 23% [386 of 1,680] with beta-lactam/fluoroquinolone; risk ratio, 0.83; 95% CI, 0.67-1.03; p = 0.09; I = 25%). When adjusted risk estimates were pooled from eight studies, macrolide therapy was still associated with a significant reduction in mortality (risk ratio, 0.75; 95% CI, 0.58-0.96; p = 0.02; I = 57%).In observational studies of almost 10,000 critically ill patients with community-acquired pneumonia, macrolide use was associated with a significant 18% relative (3% absolute) reduction in mortality compared with nonmacrolide therapies. After pooling data from studies that provided adjusted risk estimates, an even larger mortality reduction was observed. These results suggest that macrolides be considered first-line combination treatment in critically ill patients with community-acquired pneumonia and support current guidelines.

OBJECTIVE: Brief intervention (BI) is recommended for use with youth who use alcohol and other drugs. Emergency departments (EDs) can provide BIs at a time directly linked to harmful and hazardous use. The objective of this systematic review was to determine the effectiveness of ED-based BIs. METHODS: We searched 14 electronic databases, a clinical trial registry, conference proceedings, and study references. We included randomized controlled trials with youth 21 years or younger. Two reviewers independently selected studies and assessed methodological quality. One reviewer extracted and a second verified data. We summarized findings qualitatively. RESULTS: Two trials with low risk of bias, 2 trials with unclear risk of bias, and 5 trials with high risk of bias were included. Trials evaluated targeted BIs for alcohol-positive (n = 3) and alcohol/other drug-positive youth (n = 1) and universal BIs for youth reporting recent alcohol (n = 4) or cannabis use (n = 1). Few differences were found in favor of ED-based BIs, and variation in outcome measurement and poor study quality precluded firm conclusions for many comparisons. Universal and targeted BIs did not significantly reduce alcohol use more than other care. In one targeted BI trial with high risk of bias, motivational interviewing (MI) that involved parents reduced drinking quantity per occasion and high-volume alcohol use compared with MI that was delivered to youth only. Another trial with high risk of bias reported an increase in abstinence and reduction in physical altercations when youth received peer-delivered universal MI for cannabis use. In 2 trials with unclear risk of bias, MI reduced drinking and driving and alcohol-related injuries after the ED visit. Computer-based MI delivered universally in 1 trial with low risk of bias reduced alcohol-related consequences 6 months after the ED visit. CONCLUSIONS: Clear benefits of using ED-based BI to reduce alcohol and other drug use and associated injuries or high-risk behaviours remain inconclusive because of variation in assessing outcomes and poor study quality. Language: en

To evaluate the safety and efficacy of febuxostat compared to allopurinol for the treatment of chronic gout.We did a systematic review and meta-analysis of randomized and non-randomized controlled trials that compared oral febuxostat to oral allopurinol for treatment of chronic gout. Two reviewers independently selected studies, assessed study quality, and extracted data. Risk ratios (RR) were calculated with random effects and were reported with corresponding 95% confidence intervals (CI).From 1076 potentially relevant citations, 7 studies and 25 associated publications met inclusion criteria; 5 studies were ultimately included in the analysis. Febuxostat did not reduce the risk of gout flares compared with allopurinol (RR = 1.16, 95% CI = 1.03-1.30, I(2) = 44%). Overall, the risk of any adverse event was lower in febuxostat recipients compared to allopurinol (RR = 0.94, 95% CI = 0.90-0.99, I(2) = 13%). Patients receiving febuxostat were more likely to achieve a serum uric acid of6 mg/dl than allopurinol recipients (RR = 1.56, 95% CI = 1.22-2.00, I(2) = 92%). Subgroup analysis did not indicate any significant difference between high- and low-dose febuxostat on the risk of gout flares.Although febuxostat was associated with higher likelihood of achieving a target serum uric acid level of6 mg/dl, there was significant heterogeneity in the pooled results. There was no evidence that febuxostat is superior to allopurinol for clinically relevant outcomes. Given its higher cost, febuxostat should not be routinely used for chronic gout.

Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd., Background: Previous systematic reviews have not shown clear benefit of glucocorticoids for acute viral bronchiolitis, but their use remains considerable. Recent large trials add substantially to current evidence and suggest novel glucocorticoid-including treatment approaches. Objectives: To review the efficacy and safety of systemic and inhaled glucocorticoids in children with acute viral bronchiolitis. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 12), MEDLINE (1950 to January week 2, 2013), EMBASE (1980 to January 2013), LILACS (1982 to January 2013), Scopus® (1823 to January 2013) and IRAN MedEx (1998 to November 2009). Selection criteria: Randomised controlled trials (RCTs) comparing short-term systemic or inhaled glucocorticoids versus placebo or another intervention in children under 24 months with acute bronchiolitis (first episode with wheezing). Our primary outcomes were: admissions by days 1 and 7 for outpatient studies; and length of stay (LOS) for inpatient studies. Secondary outcomes included clinical severity parameters, healthcare use, pulmonary function, symptoms, quality of life and harms. Data collection and analysis: Two authors independently extracted data on study and participant characteristics, interventions and outcomes. We assessed risk of bias and graded strength of evidence. We meta-analysed inpatient and outpatient results separately using random-effects models. We pre-specified subgroup analyses, including the combined use of bronchodilators used in a protocol. Main results: We included 17 trials (2596 participants); three had low overall risk of bias. Baseline severity, glucocorticoid schemes, comparators and outcomes were heterogeneous. Glucocorticoids did not significantly reduce outpatient admissions by days 1 and 7 when compared to placebo (pooled risk ratios (RRs) 0.92; 95% confidence interval (CI) 0.78 to 1.08 and 0.86; 95% CI 0.7 to 1.06, respectively). There was no benefit in LOS for inpatients (mean difference -0.18 days; 95% CI -0.39 to 0.04). Unadjusted results from a large factorial low risk of bias RCT found combined high-dose systemic dexamethasone and inhaled epinephrine reduced admissions by day 7 (baseline risk of admission 26%; RR 0.65; 95% CI 0.44 to 0.95; number needed to treat 11; 95% CI 7 to 76), with no differences in short-term adverse effects. No other comparisons showed relevant differences in primary outcomes. Authors' conclusions: Current evidence does not support a clinically relevant effect of systemic or inhaled glucocorticoids on admissions or length of hospitalisation. Combined dexamethasone and epinephrine may reduce outpatient admissions, but results are exploratory and safety data limited. Future research should further assess the efficacy, harms and applicability of combined therapy.

Macrolides are used to treat pneumonia despite increasing antimicrobial resistance. However, the immunomodulatory properties of macrolides may have a favorable effect on pneumonia outcomes. Therefore, we systematically reviewed all studies of macrolide use and mortality among patients hospitalized with community-acquired pneumonia (CAP).All randomized control trials (RCTs) and observational studies comparing macrolides to other treatment regimens in adults hospitalized with CAP were identified through electronic databases and gray literature searches. Primary analysis examined any macrolide use and mortality; secondary analysis compared Infectious Diseases Society of America/American Thoracic Society guideline-concordant macrolide/beta-lactam combinations vs respiratory fluoroquinolones. Random effects models were used to generate pooled risk ratios (RRs) and evaluate heterogeneity (I(2)).We included 23 studies and 137,574 patients. Overall, macrolide use was associated with a statistically significant mortality reduction compared with nonmacrolide use (3.7% [1738 of 47,071] vs 6.5% [5861 of 90,503]; RR, 0.78; 95% confidence interval [CI], .64-.95; P = .01; I(2)= 85%). There was no survival advantage and heterogeneity was reduced when analyses were restricted to RCTs (4.6% [22 of 479] vs 4.1% [25 of 613]; RR, 1.13; 95% CI, .65-1.98; P = .66; I(2)= 0%) or to patients treated with guideline-concordant antibiotics (macrolide/beta-lactam, 5.3% [297 of 5574] vs respiratory fluoroquinolones, 5.8% [408 of 7050]; RR, 1.17; 95% CI, .91-1.50; P = .22; I(2)= 43%).In hospitalized patients with CAP, macrolide-based regimens were associated with a significant 22% reduction in mortality compared with nonmacrolides; however, this benefit did not extend to patients studied in RCTs or patients that received guideline-concordant antibiotics. Our findings suggest guideline concordance is more important than choice of antibiotic when treating CAP.

Aims To determine whether data from observational studies supports the hypothesis of an increased risk of overall and site-specific cancer among individuals with diabetes using exogenous insulin therapies. Methods We conducted a comprehensive search of nine key biomedical databases for all years up to December 2011, restricted to the English language. Data from cohort and nested case-control studies were included in random effects meta-analyses of site-specific and overall cancer incidence comparing ever use and new use of: (1) insulin to no insulin and; (2) insulin glargine to other insulins. Results The search yielded 3052 unique citations, of which 19 were selected for inclusion, representing data for 1,332,120 people and 41,947 cancers. Pancreatic cancer risk was increased among new users of insulin (RR: 3.18, 95%CI: 3.27–3.71, I 2 =32%). New use of insulin glargine was associated with an increased risk of pancreatic cancer (RR: 1.63, 95%CI: 1.05–2.51, I 2 =0%) and prostate cancers (RR: 2.68, 95%CI: 1.50–4.79, I 2 =0%) but a decreased risk of colorectal cancer (RR: 0.78, 95%CI: 0.64–0.94, I 2 =15%). Conclusion New use of insulin or insulin glargine was associated with an increased risk of pancreatic cancer, possibly due to reverse causality. New use of insulin glargine was associated with a decreased risk of colorectal cancer but an increased risk of prostate cancer. Our results should be interpreted with caution due to limitations of included studies.

Background Bronchodilators are commonly used for acute bronchiolitis, despite uncertain effectiveness. Objectives To examine the efficacy and safety of epinephrine in children less than two with acute viral bronchiolitis. Search methods We searched CENTRAL (2010, Issue 3) which contains the Acute Respiratory Infections Group's Specialized Register, MEDLINE (1950 to September Week 2, 2010), EMBASE (1980 to September 2010), Scopus (1823 to September 2010), PubMed (March 2010), LILACS (1985 to September 2010) and Iran MedEx (1998 to September 2010). Selection criteria We included randomized controlled trials comparing epinephrine to placebo or another intervention involving children less than two years with acute viral bronchiolitis. Studies were included if the trials presented data for at least one quantitative outcome of interest. We selected primary outcomes a priori, based on clinical relevance: rate of admission by days one and seven of presentation for outpatients, and length of stay (LOS) for inpatients. Secondary outcomes included clinical severity scores, pulmonary function, symptoms, quality of life and adverse events. Data collection and analysis Two review authors independently screened the searches, applied inclusion criteria, assessed risk of bias and graded the evidence. We conducted separate analyses for different comparison groups (placebo, non-epinephrine bronchodilators, glucocorticoids) and for clinical setting (inpatient, outpatient). Main results We included 19 studies (2256 participants). Epinephrine versus placebo among outpatients showed a significant reduction in admissions at Day 1 (risk ratio (RR) 0.67; 95% confidence interval (CI) 0.50 to 0.89) but not at Day 7 post-emergency department visit. There was no difference in LOS for inpatients. Epinephrine versus salbutamol showed no differences among outpatients for admissions at Day 1 or 7. Inpatients receiving epinephrine had a significantly shorter LOS compared to salbutamol (mean difference -0.28; 95% CI -0.46 to -0.09). One large RCT showed a significantly shorter admission rate at Day 7 for epinephrine and steroid combined versus placebo (RR 0.65; 95% CI 0.44 to 0.95). There were no important differences in adverse events. Authors' conclusions This review demonstrates the superiority of epinephrine compared to placebo for short-term outcomes for outpatients, particularly in the first 24 hours of care. Exploratory evidence from a single study suggests benefits of epinephrine and steroid combined for later time points. More research is required to confirm the benefits of combined epinephrine and steroids among outpatients. There is no evidence of effectiveness for repeated dose or prolonged use of epinephrine or epinephrine and dexamethasone combined among inpatients.

Background Randomized controlled trials (RCTs) are the gold standard for trials assessing the effects of therapeutic interventions; therefore it is important to understand how they are conducted. Our objectives were to provide an overview of a representative sample of pediatric RCTs published in 2007 and assess the validity of their results. Methods We searched Cochrane Central Register of Controlled Trials using a pediatric filter and randomly selected 300 RCTs published in 2007. We extracted data on trial characteristics; outcomes; methodological quality; reporting; and registration and protocol characteristics. Trial registration and protocol availability were determined for each study based on the publication, an Internet search and an author survey. Results Most studies (83%) were efficacy trials, 40% evaluated drugs, and 30% were placebo-controlled. Primary outcomes were specified in 41%; 43% reported on adverse events. At least one statistically significant outcome was reported in 77% of trials; 63% favored the treatment group. Trial registration was declared in 12% of publications and 23% were found through an Internet search. Risk of bias (ROB) was high in 59% of trials, unclear in 33%, and low in 8%. Registered trials were more likely to have low ROB than non-registered trials (16% vs. 5%; p = 0.008). Effect sizes tended to be larger for trials at high vs. low ROB (0.28, 95% CI 0.21,0.35 vs. 0.16, 95% CI 0.07,0.25). Among survey respondents (50% response rate), the most common reason for trial registration was a publication requirement and for non-registration, a lack of familiarity with the process. Conclusions More than half of this random sample of pediatric RCTs published in 2007 was at high ROB and three quarters of trials were not registered. There is an urgent need to improve the design, conduct, and reporting of child health research.

The objectives are: (1) To assess diagnostic test characteristics of six alternative index tests compared with the selected reference standard-a standardized exercise challenge test (ECT) in patients with suspected exercise-induced bronchoconstriction or asthma (EIB/EIA); (2) to determine the efficacy of a single prophylactic dose of four pharmacologic and one nonpharmacologic interventions vs. placebo to attenuate EIB/EIA in patients with diagnosed EIB/EIA; and (3) to determine if regular daily treatment with short-acting or long-acting beta-agonists (SABA or LABA) causes patients with EIA to develop tachyphylaxis when additional prophylactic doses are used pre-exercise.A systematic and comprehensive literature search was conducted in 14 electronic databases (Diagnosis) and the Cochrane Airways Register (Therapy).Study selection, quality assessment, and data extraction were conducted independently by two reviewers. The primary outcome was the maximum percent fall in the post-exercise forced expiratory volume in 1 second (percent fall FEV1). The diagnostic threshold for a positive ECT was a percent fall FEV1 of 10% or more. Sensitivity (SN) and specificity (SP) were calculated. For therapy, mean differences (MD) in the percent fall FEV1 and 95% confidence intervals (CI) (random effects model) were calculated. A positive MD indicates the intervention works better than the control.For the diagnostic reviews, 5,318 citations yielded 28 relevant studies; for the therapy reviews, 1,634 citations yielded 109 relevant RCTs. Diagnostic test results versus ECT: self-reported history (2 studies) SN=36-8 percent; SP=85-86 percent; sport specific challenges (5 studies) SN=0-100 percent, SP=0-100 percent; eucapnic voluntary hyperpnea (7 studies) SN=25-90 percent, SP=0-71 percent; free running asthma screening test (3 studies) SN=60-67 percent, SP=47-67 percent; mannitol (3 studies) SN=58-96 percent, SP=65-78 percent. All SN and SP calculations indicated substantial heterogeneity that could not be explained by sensitivity or subgroup analyses. Therapy results: SABA offered greater protection than mast cell stabilizers (MCS) (12 studies); MD=6.8 (95 percent CI: 4.5, 9.2) but combining them offered no additional benefit; SABA versus MCS plus SABA (5 studies) MD=1.3 (95 percent CI: -6.3, 8.9). Leukotriene receptor antagonists (LTRA), MCS, ipratropium bromide, and interval warmup routines provided statistically significant attenuation of EIA when compared with placebo; inhaled corticosteroids (ICS) and other warmup routines did not. Single-dose intervention versus placebo results are: LTRA (9 studies) MD=8.9 (95 percent CI: 6.9, 11.0); MCS (nedocromil sodium) (17 studies) MD=15.6 (95 percent CI: 13.2, 18.2); interval warmup versus no warmup (4 studies) MD=10.6 (95 percent CI: 6.5, 14.7); ICS (4 studies) MD=5.0 (95 percent CI: 0.0, 9.9); continuous low intensity warmup versus no warmup (3 studies) MD=12.6 (95 percent CI: -1.5, 26.7); continuous high intensity warmup versus no warmup (2 studies) MD=9.8 (95 percent CI: -6.4, 26.0). After daily LABA (salmeterol) use for 3 to 4 weeks (4 studies), the percent fall FEV1 following an ECT at 2 and 4 weeks was greater than at day 1 in the LABA arm indicating that tachyphylaxis to prophylactic LABA use occurred. Daily SABA use for 1 week (1 study) also indicated development of tachyphylaxis. However, both LABA and SABA continued to have an attenuating effect on EIA.Given the small number of studies comparing EIB/EIA diagnostic tests, the heterogeneity of the study populations, and the varied study methodologies, there is no clear evidence that any of the index tests are a suitable replacement for a standardized ECT to diagnose EIB/EIA in the general population. All bronchodilator agents and most anti-inflammatory agents when used as pretreatment are somewhat effective in attenuating the percent fall FEV1 associated with EIA.

Many approaches exist for managing rotator cuff tears.To compare the benefits and harms of nonoperative and operative interventions on clinically important outcomes in adults with rotator cuff tears.12 electronic databases (1990 to September 2009), gray literature, trial registries, and reference lists were searched.Controlled and uncontrolled studies that assessed nonoperative or operative treatments or postoperative rehabilitation for adults with confirmed rotator cuff tears were included. Operative studies in English-language publications and nonoperative and postoperative rehabilitation studies in English, French, or German were considered. Studies were assessed in duplicate.2 reviewers assessed risk for bias by using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale. One reviewer rated the evidence by using a modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Data were extracted by one reviewer and verified by another.137 studies met eligibility criteria. All trials had high risk for bias. Cohort and uncontrolled studies were of moderate quality. Reported functional outcomes did not differ between open versus mini-open repair, mini-open versus arthroscopic repair, arthroscopic repair with versus without acromioplasty, or single-row versus double-row fixation. Earlier return to work was reported for mini-open repair versus open repair and for continuous passive motion with physical therapy versus physical therapy alone. Open repairs showed greater improvement in function than did arthroscopic debridement. Complication rates were low across all interventions.Limited evidence, which was often of low quality, precluded conclusions for most comparisons. Language restrictions may have excluded some relevant studies, and selective outcome reporting may have introduced bias.Evidence on the comparative effectiveness and harms of various operative and nonoperative treatments for rotator cuff tears is limited and inconclusive.Agency for Healthcare Research and Quality.

Chronic illness or disability in children can have a deleterious effect on the psychosocial health of well siblings. This systematic review synthesised evidence from studies evaluating sibling-oriented care aimed at improving behavioural and emotional outcomes in well siblings of children with chronic illness or disability. Twenty electronic databases were searched. Study selection, data extraction and assessment of methodological quality were performed by two independent reviewers. Five controlled and nine uncontrolled studies were included. In higher-quality controlled trials, benefits of sibling-oriented care included reduced anxiety, improved mood and behavioural adjustment; however, these findings were not consistently demonstrated across studies. Study differences made it difficult to determine which sibling care features were most salient. Study findings highlight the potential for enhancing emotional and behavioural outcomes in well siblings. Future evaluations need to clearly identify the intended purpose of the care (what improvements are intended) and which types of siblings are most likely to benefit. This approach may yield more consistent and clinically important results.

BackgroundCurrent guidelines recommend children be treated for hepatitis C virus (HCV) using the same principles applied in adults. There are however few published studies which assess the efficacy and safety of HCV therapy in children.Methodology/principal findingsA systematic review of the literature was completed for studies of any design that evaluated HCV therapy in children. The primary outcome was sustained virologic response (SVR), with sub-group analysis of response rates by genotype. There were 4 randomized controlled trials (RCTs) and 31 non-randomized studies, all involving interferon, pegylated interferon (PEG-IFN), or combinations of these drugs with ribavirin. The SVR rate could not be directly compared as the populations and interventions differed across studies. Genotype was not reported or differed substantially from study to study. The overall SVR rate for PEG-IFN and ribavirin ranged from 30 to 100% which is comparable to the rate in adults. Similar to adults, the SVR rates were significantly higher in children with genotype 2 or 3 compared to genotype 1. Adverse effects were primarily flu-like symptoms and neutropenia. There were insufficient data to assess the applicability of the week 12 stop rule (stopping therapy at week 12 if there is less than a 2 log drop in HCV RNA) or the efficacy of shortening therapy to 24 weeks in children with genotype 2 and 3.Conclusions/significanceCurrent guidelines for the treatment of HCV in children are based on limited data. Further research is needed to define the optimal therapy for HCV in children.

Background Systematic reviews (SRs) are considered an important tool for decision-making. There has been no recent comprehensive identification or description of child-relevant SRs. A description of existing child-relevant SRs would help to identify the extent of available child-relevant evidence available in SRs and gaps in the evidence base where SRs are required. The objective of this study was to describe child-relevant SRs from the Cochrane Database of Systematic Reviews (CDSR, Issue 2, 2009). Methods SRs were assessed for relevance using pre-defined criteria. Data were extracted and entered into an electronic form. Univariate analyses were performed to describe the SRs overall and by topic area. Results The search yielded 1666 SRs; 793 met the inclusion criteria. 38% of SRs were last assessed as up-to-date prior to 2007. Corresponding authors were most often from the UK (41%). Most SRs (59%) examined pharmacological interventions. 53% had at least one external source of funding. SRs included a median of 7 studies (IQR 3, 15) and 679 participants (IQR 179, 2833). Of all studies, 48% included only children, and 27% only adults. 94% of studies were published in peer-reviewed journals. Primary outcomes were specified in 72% of SRs. Allocation concealment and the Jadad scale were used in 97% and 25% of SRs, respectively. Adults and children were analyzed separately in 12% of SRs and as a subgroup analysis in 14%. Publication bias was assessed in only 14% of SRs. A meta-analysis was conducted in 68% of SRs with a median of 5 trials (IQR 3, 9) each. Variations in these characteristics were observed across topic areas. Conclusions We described the methodological characteristics and rigour of child-relevant reviews in the CDSR. Many SRs are not up-to-date according to Cochrane criteria. Our study describes variation in conduct and reporting across SRs and reveals clinicians' ability to access child-specific data.

Study objective We evaluate the effectiveness of interventions for pediatric patients with suicide-related emergency department (ED) visits. Methods We searched of MEDLINE, EMBASE, the Cochrane Library, other electronic databases, references, and key journals/conference proceedings. We included experimental or quasiexperimental studies that evaluated psychosocial interventions for pediatric suicide-related ED visits. Inclusion screening, study selection, and methodological quality were assessed by 2 independent reviewers. One reviewer extracted the data and a second checked for completeness and accuracy. Consensus was reached by conference; disagreements were adjudicated by a third reviewer. We calculated odds ratios, relative risks (RRs), or mean differences for each study's primary outcome, with 95% confidence intervals (CIs). Meta-analysis was deferred because of clinical heterogeneity in intervention, patient population, and outcome. Results We included 7 randomized controlled trials and 3 quasiexperimental studies, grouping and reviewing them according to intervention delivery: ED-based delivery (n=1), postdischarge delivery (n=6), and ED transition interventions (n=3). An ED-based discharge planning intervention increased the number of attended post-ED treatment sessions (mean difference=2.6 sessions; 95% CI 0.05 to 5.15 sessions). Of the 6 studies of postdischarge delivery interventions, 1 found increased adherence with service referral in patients who received community nurse home visits compared with simple placement referral at discharge (RR=1.28; 95% CI 1.06 to 1.56). The 3 ED transition intervention studies reported (1) reduced risk of subsequent suicide after brief ED intervention and postdischarge contact (RR=0.10; 95% CI 0.03 to 0.41); (2) reduced suicide-related hospitalizations when ED visits were followed up with interim, psychiatric care (RR=0.41; 95% CI 0.28 to 0.60); and (3) increased likelihood of treatment completion when psychiatric evaluation in the ED was followed by attendance of outpatient sessions with a parent (odds ratio=2.78; 95% CI 1.20 to 6.67). Conclusion Transition interventions appear most promising for reducing suicide-related outcomes and improving post-ED treatment adherence. Use of similar interventions and outcome measures in future studies would enhance the ability to derive strong recommendations from the clinical evidence in this area.

Purpose: To conduct a systematic review of problem-based learning (PBL) in undergraduate, pre-clinical medical education. Methods: A research librarian developed comprehensive search strategies for MEDLINE, PSYCINFO, and ERIC (1985–2007). Two reviewers independently screened search results and applied inclusion criteria. Studies were included if they had a comparison group and reported primary data for evaluative outcomes. One reviewer extracted data and a second reviewer checked data for accuracy. Two reviewers independently assessed methodological quality. Quantitative synthesis was not performed due to heterogeneity. A qualitative review with detailed evidence tables is provided. Results: Thirty unique studies were included. Knowledge acquisition measured by exam scores was the most frequent outcome reported; 12 of 15 studies found no significant differences. Individual studies demonstrated either improved clerkship (N ¼ 3) or residency (N ¼ 1) performance, or benefits on some clinical competencies during internships for PBL (N ¼ 1). Three of four studies found some benefits for PBL when evaluating diagnostic accuracy. Three studies found few differences of clinical (or practical) importance on the impact of PBL on practicing physicians. Conclusions: Twenty-two years of research shows that PBL does not impact knowledge acquisition; evidence for other outcomes does not provide unequivocal support for enhanced learning. Work is needed to determine the most appropriate outcome measures to capture and quantify the effects of PBL. General conclusions are limited by methodological weaknesses and heterogeneity across studies. The critical appraisal of previous studies, conducted as part of this review, provides direction for future research in this area.

Background The objective of this study was to describe randomized controlled trials (RCTs) and controlled clinical trials (CCTs) in child health published between 1948 and 2006, in terms of quantity, methodological quality, and publication and trial characteristics. We used the Trials Register of the Cochrane Child Health Field for overall trends and a sample from this to explore trial characteristics in more detail. Methodology/Principal Findings We extracted descriptive data on a random sample of 578 trials. Ninety-six percent of the trials were published in English; the percentage of child-only trials was 90.5%. The most frequent diagnostic categories were infectious diseases (13.2%), behavioural and psychiatric disorders (11.6%), neonatal critical care (11.4%), respiratory disorders (8.9%), non-critical neonatology (7.9%), and anaesthesia (6.5%). There were significantly fewer child-only studies (i.e., more mixed child and adult studies) over time (P = 0.0460). The proportion of RCTs to CCTs increased significantly over time (P

Background Nutritional support in the critically ill child has not been well investigated and is a controversial topic within paediatric intensive care. There are no clear guidelines as to the best form or timing of nutrition in critically ill infants and children. This is an update of a review that was originally published in 2009. . Objectives The objective of this review was to assess the impact of enteral and parenteral nutrition given in the first week of illness on clinically important outcomes in critically ill children. There were two primary hypotheses: 1. the mortality rate of critically ill children fed enterally or parenterally is different to that of children who are given no nutrition; 2. the mortality rate of critically ill children fed enterally is different to that of children fed parenterally. We planned to conduct subgroup analyses, pending available data, to examine whether the treatment effect was altered by: a. age (infants less than one year versus children greater than or equal to one year old); b. type of patient (medical, where purpose of admission to intensive care unit (ICU) is for medical illness (without surgical intervention immediately prior to admission), versus surgical, where purpose of admission to ICU is for postoperative care or care after trauma). We also proposed the following secondary hypotheses (a priori), pending other clinical trials becoming available, to examine nutrition more distinctly: 3. the mortality rate is different in children who are given enteral nutrition alone versus enteral and parenteral combined; 4. the mortality rate is different in children who are given both enteral feeds and parenteral nutrition versus no nutrition. Search methods In this updated review we searched: the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2); Ovid MEDLINE (1966 to February 2016); Ovid EMBASE (1988 to February 2016); OVID Evidence-Based Medicine Reviews; ISI Web of Science - Science Citation Index Expanded (1965 to February 2016); WebSPIRS Biological Abstracts (1969 to February 2016); and WebSPIRS CAB Abstracts (1972 to February 2016). We also searched trial registries, reviewed reference lists of all potentially relevant studies, handsearched relevant conference proceedings, and contacted experts in the area and manufacturers of enteral and parenteral nutrition products. We did not limit the search by language or publication status. Selection criteria We included studies if they were randomized controlled trials; involved paediatric patients, aged one day to 18 years of age, who were cared for in a paediatric intensive care unit setting (PICU) and had received nutrition within the first seven days of admission; and reported data for at least one of the pre-specified outcomes (30-day or PICU mortality; length of stay in PICU or hospital; number of ventilator days; and morbid complications, such as nosocomial infections). We excluded studies if they only reported nutritional outcomes, quality of life assessments, or economic implications. Furthermore, we did not address other areas of paediatric nutrition, such as immunonutrition and different routes of delivering enteral nutrition, in this review. Data collection and analysis Two authors independently screened the searches, applied the inclusion criteria, and performed 'Risk of bias' assessments. We resolved discrepancies through discussion and consensus. One author extracted data and a second checked data for accuracy and completeness. We graded the evidence based on the following domains: study limitations, consistency of effect, imprecision, indirectness, and publication bias. Main results We identified only one trial as relevant. Seventy-seven children in intensive care with burns involving more than 25% of the total body surface area were randomized to either enteral nutrition within 24 hours or after at least 48 hours. No statistically significant differences were observed for mortality, sepsis, ventilator days, length of stay, unexpected adverse events, resting energy expenditure, nitrogen balance, or albumin levels. We assessed the trial as having unclear risk of bias. We consider the quality of the evidence to be very low due to there being only one small trial. In the most recent search update we identified a protocol for a relevant randomized controlled trial examining the impact of withholding early parenteral nutrition completing enteral nutrition in pediatric critically ill patients; no results have been published. Authors' conclusions There was only one randomized trial relevant to the review question. Research is urgently needed to identify best practices regarding the timing and forms of nutrition for critically ill infants and children.

BackgroundMuch controversy exists regarding the clinical efficacy of behavioural and developmental interventions for improving the core symptoms of autism spectrum disorders (ASD). We conducted a systematic review to summarize the evidence on the effectiveness of behavioural and developmental interventions for ASD.Methods and findingsComprehensive searches were conducted in 22 electronic databases through May 2007. Further information was obtained through hand searching journals, searching reference lists, databases of theses and dissertations, and contacting experts in the field. Experimental and observational analytic studies were included if they were written in English and reported the efficacy of any behavioural or developmental intervention for individuals with ASD. Two independent reviewers made the final study selection, extracted data, and reached consensus on study quality. Results were summarized descriptively and, where possible, meta-analyses of the study results were conducted. One-hundred-and-one studies at predominantly high risk of bias that reported inconsistent results across various interventions were included in the review. Meta-analyses of three controlled clinical trials showed that Lovaas treatment was superior to special education on measures of adaptive behaviour, communication and interaction, comprehensive language, daily living skills, expressive language, overall intellectual functioning and socialization. High-intensity Lovaas was superior to low-intensity Lovaas on measures of intellectual functioning in two retrospective cohort studies. Pooling the results of two randomized controlled trials favoured developmental approaches based on initiative interaction compared to contingency interaction in the amount of time spent in stereotyped behaviours and distal social behaviour, but the effect sizes were not clinically significant. No statistically significant differences were found for: Lovaas versus special education for non-verbal intellectual functioning; Lovaas versus Developmental Individual-difference relationship-based intervention for communication skills; computer assisted instruction versus no treatment for facial expression recognition; and TEACCH versus standard care for imitation skills and eye-hand integration.ConclusionsWhile this review suggests that Lovaas may improve some core symptoms of ASD compared to special education, these findings are based on pooling of a few, methodologically weak studies with few participants and relatively short-term follow-up. As no definitive behavioural or developmental intervention improves all symptoms for all individuals with ASD, it is recommended that clinical management be guided by individual needs and availability of resources.

Observational studies report consistent associations between low vitamin D concentration and increased glycemia and risk of type 2 diabetes, but results of randomized controlled trials (RCTs) are mixed.The objective of the study was to systematically review RCTs that report on the effects of vitamin D supplementation on glucose homeostasis or diabetes prevention.Sources of data for the study were MEDLINE, EMBASE, SCOPUS, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment, and Science Citation Index from inception to June 2013.Study selection was trials that compared vitamin D3 supplementation with placebo or a non-vitamin D supplement in adults with normal glucose tolerance, prediabetes, or type 2 diabetes.Two reviewers collected data and assessed trial quality using the Cochrane Risk of Bias tool. Random-effects models were used to estimate mean differences (MDs) and odds ratios. The main outcomes of interest were homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function, hemoglobin A1c levels, fasting blood glucose, incident diabetes, and adverse events.Thirty-five trials (43 407 patients) with variable risk of bias were included. Vitamin D had no significant effects on insulin resistance [homeostasis model assessment of insulin resistance: MD -0.04; 95% confidence interval (CI) -0.30 to 0.22, I-squared statistic (I(2)) = 45%], insulin secretion (homeostasis model of β-cell function: MD 1.64; 95% CI -25.94 to 29.22, I(2) = 40%), or hemoglobin A1c (MD -0.05%; 95% CI -0.12 to 0.03, I(2) = 55%) compared with controls. Four RCTs reported on the progression to new diabetes and found no effect of vitamin D (odds ratio 1.02; 95% CI 0.94 to 1.10, I(2) = 0%). Adverse events were rare, and there was no evidence of publication bias.Evidence from available trials shows no effect of vitamin D3 supplementation on glucose homeostasis or diabetes prevention. Definitive conclusions may be limited in the context of the moderate degree of heterogeneity, variable risk of bias, and short-term follow-up duration of the available evidence to date.

Objective To conduct a systematic review of the efficacy and safety of exogenous melatonin in managing secondary sleep disorders and sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder. Data sources 13 electronic databases and reference lists of relevant reviews and included studies; Associated Professional Sleep Society abstracts (1999 to 2003). Study selection The efficacy review included randomised controlled trials; the safety review included randomised and non-randomised controlled trials. Quality assessment Randomised controlled trials were assessed by using the Jadad Scale and criteria by Schulz et al, and non-randomised controlled trials by the Downs and Black checklist. Data extraction and synthesis One reviewer extracted data and another reviewer verified the data extracted. The inverse variance method was used to weight studies and the random effects model was used to analyse data. Main results Six randomised controlled trials with 97 participants showed no evidence that melatonin had an effect on sleep onset latency in people with secondary sleep disorders (weighted mean difference −13.2 (95% confidence interval −27.3 to 0.9) min). Nine randomised controlled trials with 427 participants showed no evidence that melatonin had an effect on sleep onset latency in people who had sleep disorders accompanying sleep restriction (−1.0 (−2.3 to 0.3) min). 17 randomised controlled trials with 651 participants showed no evidence of adverse effects of melatonin with short term use (three months or less). Conclusions There is no evidence that melatonin is effective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder. There is evidence that melatonin is safe with short term use.

Exogenous melatonin has been increasingly used in the management of sleep disorders.To conduct a systematic review of the efficacy and safety of exogenous melatonin in the management of primary sleep disorders.A number of electronic databases were searched. We reviewed the bibliographies of included studies and relevant reviews and conducted hand-searching.Randomized controlled trials (RCTs) were eligible for the efficacy review, and controlled trials were eligible for the safety review.One reviewer extracted data, while the other verified data extracted. The Random Effects Model was used to analyze data.Melatonin decreased sleep onset latency (weighted mean difference [WMD]: -11.7 minutes; 95% confidence interval [CI]: -18.2, -5.2)); it was decreased to a greater extent in people with delayed sleep phase syndrome (WMD: -38.8 minutes; 95% CI: -50.3, -27.3; n=2) compared with people with insomnia (WMD: -7.2 minutes; 95% CI: -12.0, -2.4; n=12). The former result appears to be clinically important. There was no evidence of adverse effects of melatonin.There is evidence to suggest that melatonin is not effective in treating most primary sleep disorders with short-term use (4 weeks or less); however, additional large-scale RCTs are needed before firm conclusions can be drawn. There is some evidence to suggest that melatonin is effective in treating delayed sleep phase syndrome with short-term use. There is evidence to suggest that melatonin is safe with short-term use (3 months or less).

Background: Pain management is integral to the management of hip fracture. Purpose: To review the benefits and harms of pharmacologic and nonpharmacologic interventions for managing pain after hip fracture. Data Sources: 25 electronic databases (January 1990 to December 2010), gray literature, trial registries, and reference lists, with no language restrictions. Study Selection: Multiple reviewers independently, and in duplicate, screened 9357 citations to identify randomized, controlled trials (RCTs); nonrandomized, controlled trials (non-RCTs); and cohort studies of pain management techniques in older adults after acute hip fracture. Data Extraction: Independent, duplicate data extraction and quality assessment were conducted, with discrepancies resolved by consensus or a third reviewer. Data extracted included study characteristics, inclusion and exclusion criteria, participant characteristics, interventions, and outcomes. Data Synthesis: 83 unique studies (64 RCTs, 5 non-RCTs, and 14 cohort studies) that addressed the following interventions were included: nerve blockade (n = 32), spinal anesthesia (n = 30), systemic analgesia (n = 3), traction (n = 11), multimodal pain management (n = 2), neurostimulation (n = 2), rehabilitation (n = 1), and complementary and alternative medicine (n = 2). Overall, moderate evidence suggests that nerve blockades are effective for relieving acute pain and reducing delirium. Low-level evidence suggests that preoperative traction does not reduce acute pain. Evidence was insufficient about the benefits and harms of most interventions, including spinal anesthesia, systemic analgesia, multimodal pain management, acupressure, relaxation therapy, transcutaneous electrical neurostimulation, and physical therapy regimens, in managing acute pain. Limitations: No studies evaluated outcomes of chronic pain or exclusively examined participants from nursing homes or with cognitive impairment. Systemic analgesics (narcotics, nonsteroidal anti-inflammatory drugs) were understudied during the search period. Conclusion: Nerve blockade seems effective in reducing acute pain after hip fracture. Sparse data preclude firm conclusions about the relative benefits or harms of many other pain management interventions for patients with hip fracture. Primary Funding Source: Agency for Healthcare Research and Quality.

Objective The aim of this study was to conduct a systematic review of the efficacy of music therapy (MT) on pain and anxiety in children undergoing clinical procedures. Methods We searched 16 electronic databases of published and unpublished studies, subject bibliographies, reference lists of relevant articles, and trials registries. Two reviewers independently screened 4559 citations and reviewed the full manuscript of 393 studies. Nineteen studies met the inclusion criteria: randomized controlled trial, children aged 1 month to 18 years were examined, music was used as an intervention, and the study measured pain or anxiety. Music therapy was considered active if a music therapist was involved and music was used as a medium for interactive communication. Passive music therapy was defined as listening to music without the involvement of a music therapist. Results The 19 included trials involved 1513 subjects. The methodological quality of the studies was generally poor. Overall, MT showed a significant reduction in pain and anxiety (standardized mean difference [SMD] −0.35; 95% confidence interval [CI], −0.55 to −0.14; 9 studies; N=704; I 2 = 42%). When analyzed by outcome, MT significantly reduced anxiety (SMD −0.39; 95% CI, −0.76 to −0.03; 5 studies; n=284; I 2 = 52.4%) and pain (SMD −0.39; 95% CI, −0.66 to −0.11; 5 studies; N=465; I 2 = 49.7%). There was no evidence of publication bias. Conclusions Music is effective in reducing anxiety and pain in children undergoing medical and dental procedures. Music can be considered an adjunctive therapy in clinical situations that produce pain or anxiety.