Evidence available for patient-identified priorities in depression research: results of 11 rapid responses.

OBJECTIVES: Patient priority setting projects (PPSPs) can reduce research agenda bias. A key element of PPSPs is a review of available literature to determine if the proposed research priorities have been addressed, identify research gaps, recognise opportunities for knowledge translation (KT) and avoid duplication of research efforts. We conducted rapid responses for 11 patient-identified priorities in depression to provide a map of the existing evidence. DESIGN: Eleven rapid responses. DATA SOURCES: Single electronic database (PubMed). ELIGIBILITY CRITERIA: Each rapid response had unique eligibility criteria. For study designs, we used a stepwise inclusion process that started with systematic reviews (SRs) if available, then randomised controlled trials and observational studies as necessary. RESULTS: For all but one of the rapid responses we identified existing SRs (median 7 SRs per rapid response, range 0-179). There were questions where extensive evidence exists (ie, hundreds of primary studies), yet uncertainties remain. For example, there is evidence supporting the effectiveness of many non-pharmacological interventions (including psychological interventions and exercise) to reduce depressive symptoms. However, targeted research is needed that addresses comparative effectiveness of promising interventions, specific populations of interest (eg, children, minority groups) and adverse effects. CONCLUSIONS: We identified an extensive body of evidence addressing patient priorities in depression and mapped the results and limitations of existing evidence, areas of uncertainty and general directions for future research. This work can serve as a solid foundation to guide future research in depression and KT activities. Integrated knowledge syntheses bring value to the PPSP process; however, the role of knowledge synthesis in PPSPs and methodological approaches are not well defined at present.

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.

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.

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 STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, issue 4); MEDLINE (1950 to November 2009); EMBASE (1980 to Week 47 2009); LILACS (1982 to November 2009); Scopus® (1823 to November 2009); 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 < 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. Inpatient and outpatient results were meta-analysed separately using random-effects models. We pre-specified subgroup analyses, including the combined use of protocolised bronchodilators. MAIN RESULTS: We included 17 trials (2596 participants); only two 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% 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 hospitalization. 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.