A systematic review of the accessibility, acceptability, safety, efficiency, clinical effectiveness, and cost-effectiveness of private cataract and orthopedic surgery clinics.

OBJECTIVES: Many publicly funded health systems use a mix of privately and publicly operated providers of care to deliver elective surgical services. The aim of this systematic review was to assess the role of privately operated but publicly funded provision of surgical services for adult patients who had cataract or orthopedic surgery within publicly funded health systems in high-income countries. METHODS: Electronic databases (Ovid MEDLINE, OVID Embase, and EBSCO EconLit) were searched on 26 March 2021, and gray literature sources were searched on 6 April 2021. Two reviewers independently applied inclusion and exclusion criteria to identify studies, and extracted data. The outcomes evaluated include accessibility, acceptability, safety, clinical effectiveness, efficiency, and cost/cost-effectiveness. RESULTS: Twenty-nine primary studies met the inclusion criteria and were synthesized narratively. We found mixed results across each of our reported outcomes. Wait times were shorter for patients treated in private facilities. There was evidence that some private facilities cherry-pick or cream-skim by selecting less complex patients, which increases the postoperative length of stay and costs for public facilities, restricts access to private facilities for certain groups of patients, and increases inequality within the health system. Seven studies found improved safety outcomes in private facilities, noting that private patients had a lower preoperative risk of complications. Only two studies reported cost and cost-effectiveness outcomes. One costing study concluded that private facilities' costs were lower than those of public facilities, and a cost-utility study showed that private contracting to reduce public waiting times for joint replacement was cost-effective. CONCLUSIONS: Limited evidence exists that private-sector contracts address existing healthcare delivery problems. Value for money also remains to be evaluated properly.

Quality of reporting of economic evaluations in rehabilitation research: a systematic review.

BACKGROUND: The quality of reporting of health economic evaluations for rehabilitation services has been questioned, limiting the ability to provide accurate recommendations for health decisions. PURPOSE: 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. DATA SOURCES: Electronic literature searches were performed using MEDLINE and the NHS Economic Evaluations Database via the Cochrane Library. STUDY SELECTION: Prospective rehabilitation economic evaluation articles from 2013 to 2020 were selected. DATA EXTRACTION: Data were extracted by one reviewer and independently verified by a second reviewer. DATA SYNTHESIS/RESULTS: 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. LIMITATIONS: Only two databases were used in data collection, and papers were selected from 2013 to 2020 only. CONCLUSIONS: 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.

Methodological Issues in Rehabilitation Research: A Scoping Review.

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.

A systematic review of workplace behavioral interventions to promote sleep health in men.

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.

Thiazide Diuretic-Induced Change in Fasting Plasma Glucose: a Meta-analysis of Randomized Clinical Trials.

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 < 50 participants, those with a follow-up period of < 4 weeks, and conference abstracts were excluded. DATA EXTRACTION: Independent duplicate screening of citations and full-text articles, data extraction, and assessment of risk of bias was conducted. DATA SYNTHESIS: Ninety-five studies were included (N = 76,608 participants), with thiazides compared with placebo, beta-blockers, calcium channel blockers, renin-angiotensin-aldosterone-system inhibitors, potassium-sparing diuretic, and others alone or in combination. Thiazide diuretics marginally increased FPG (weighted mean difference 0.20 mmol/L (95% CI 0.15-0.25); I2 = 84%) (1 mmol/L = 18 mg/dL). Results did not change substantially when considering dose or duration, comparing thiazides with placebo or an active comparator, or using thiazides as monotherapy or combination therapy, even when combined with a potassium-correcting agent. CONCLUSION: Thiazide diuretics have a small and clinically unimportant impact on FPG.

Nursing Staff Time and Care Quality in Long-Term Care Facilities: A Systematic Review.

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.

Systematic review of community pharmacy-based and pharmacist-led foot care interventions for adults with type 2 diabetes.

BACKGROUND: To prevent diabetic foot disease, proper foot care is essential for early detection and treatment. Pharmacists are well suited to provide accessible foot care to adults with type 2 diabetes. Limited research has examined this role. METHODS: We conducted a systematic review of community pharmacy-based and pharmacist-led foot care interventions for adults with type 2 diabetes compared to usual care. Data sources included MEDLINE, EMBASE, the Cochrane Library, CINAHL, Academic Search Complete and Health Source: Nursing/Academic Edition and Google Scholar, plus Google and hand-searching. Original research studies reported in English, focused on community pharmacy-based or pharmacist-led foot care interventions were eligible for review. Participants were adults with type 2 diabetes. Studies were summarized narratively; pooled data were not possible. RESULTS: Seven studies were included in this review, 3 focusing on improving foot self-care behaviours and 4 on promoting foot examinations by the health care provider. Only 2 studies were randomized and were assessed as high quality. Six out of 7 studies reported significantly positive findings related to foot care practices. DISCUSSION: An opportunity to influence foot care exists at each clinical encounter. Pharmacists are accessible health care practitioners and appropriate to provide a range of diabetes foot care interventions. CONCLUSIONS: Seven studies examined community pharmacy-based and pharmacist-led foot care interventions for people with type 2 diabetes. Community pharmacies and pharmacists are capable of providing a variety of foot care interventions to patients with diabetes, helping detect problems early and leading to prompt intervention.

Nutritional support for critically ill children.

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.

Clinical review: Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis.

CONTEXT: 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. OBJECTIVE: 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. DATA SOURCES: 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: 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. DATA EXTRACTION AND SYNTHESIS: 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 ß-cell function, hemoglobin A1c levels, fasting blood glucose, incident diabetes, and adverse events. DATA SYNTHESIS: 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 ß-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. CONCLUSIONS: 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.

Cardiovascular medication utilization and adherence among adults living in rural and urban areas: a systematic review and meta-analysis.

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 (I(2) = 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, I(2) = 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.

A systematic review of interventions to support siblings of children with chronic illness or disability.

AIM: 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. METHODS: Twenty electronic databases were searched. Study selection, data extraction and assessment of methodological quality were performed by two independent reviewers. RESULTS: 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. CONCLUSIONS: 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.

Macrolides and mortality in critically ill patients with community-acquired pneumonia: a systematic review and meta-analysis.

OBJECTIVE: 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. DATA SOURCES: Studies were identified via electronic databases, grey literature, and conference proceedings through May 2013. STUDY SELECTION: Using prespecified criteria, two reviewers selected studies; studies of outpatients and hospitalized noncritically ill patients were excluded. DATA EXTRACTION: 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). DATA SYNTHESIS: 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%). CONCLUSIONS: 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.

A systematic review and meta-analysis on the safety and efficacy of febuxostat versus allopurinol in chronic gout.

OBJECTIVE: To evaluate the safety and efficacy of febuxostat compared to allopurinol for the treatment of chronic gout. METHODS: 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). RESULTS: 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 of <6 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. CONCLUSION: Although febuxostat was associated with higher likelihood of achieving a target serum uric acid level of <6 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.

Glucocorticoids for acute viral bronchiolitis in infants and young children.

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.

Brief emergency department interventions for youth who use alcohol and other drugs: a systematic review.

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.

Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients.

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<0.001). No increased risk was observed for metformin in those with reduced left ventricular ejection fraction (mortality pooled adjusted risk estimate: 0.91; 0.72-1.14; 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.

The nature and influence of pharmaceutical industry involvement in asthma trials.

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 chi squared test 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.

Macrolide-based regimens and mortality in hospitalized patients with community-acquired pneumonia: a systematic review and meta-analysis.

BACKGROUND: 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). METHODS: 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)). RESULTS: 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%). CONCLUSIONS: 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.

Comparative effectiveness of pain management interventions for hip fracture: a systematic review.

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) were included that addressed 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 on 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 to be 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.

Epinephrine for bronchiolitis.

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 STRATEGY: 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.