Background: Frequent users of health care services are a relatively small group of patients who account for a disproportionately large amount of health care utilization. We conducted a metaanalysis of the effectiveness of interventions to improve the coordination of care to reduce health care utilization in this patient group. Methods:We searched MEDLINE, Embase and the Cochrane Library from inception until May 2014 for randomized clinical trials (RCTs) assessing quality improvement strategies for the coordination of care of frequent users of the health care system. Articles were screened, and data abstracted and appraised for quality by 2 reviewers, independently. Random effects meta-analyses were conducted. Results:We identified 36 RCTs and 14 companion reports (total 7494 patients). Significantly fewer patients in the intervention group than in the control group were admitted to hospital (relative risk [RR] 0.81, 95% confidence interval [CI] 0.72-0.91). In subgroup analyses, a similar effect was observed among patients with chronic medical conditions other than mental illness, but not among patients with mental illness. In addition, significantly fewer patients 65 years and older in the intervention group than in the control group visited emergency departments (RR 0.69, 95% CI 0.54-0.89). Interpretation:We found that quality improvement strategies for coordination of care reduced hospital admissions among patients with chronic conditions other than mental illness and reduced emergency department visits among older patients. Our results may help clinicians and policy-makers reduce utilization through the use of strategies that target the system (team changes, case management) and the patient (promotion of self-management). AbstractSee related commentary, www.cmaj.ca/lookup

Background/Objectives To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease (AD). Design Systematic review and Bayesian network metaanalysis (NMA). Setting MEDLINE, EMBASE, Cochrane Library, CINAHL, Ageline (inception–March 2016). Participants Individuals with AD in randomized controlled trials (RCTs), quasi‐RCTs, and nonrandomized studies. Intervention Any combination of donepezil, rivastigmine, galantamine, or memantine. Measurements Two reviewers independently screened titles, abstracts, and full‐texts; abstracted data; and appraised risk of bias. Results Twenty thousand three hundred forty‐three citations were screened, and 142 studies were included (110 RCTs, 21 non‐RCTs, 11 cohort studies). NMA found that donepezil (Mini‐Mental State Examination: mean difference (MD) = 1.39, 95% credible interval (CrI) = 0.53–2.24), donepezil+memantine (2.59, 95% CrI = 0.12–4.98), and transdermal rivastigmine (2.02, 95% CrI = 0.02–4.08) improved cognition more than placebo. NMA found that donepezil (Alzheimer's Disease Assessment Scale–cognitive: MD = −3.29, 95% CrI = −4.57 to −1.99) and galantamine (MD = −2.13, 95% CrI = −3.91 to −0.27) improved cognition more than placebo. NMA found that donepezil+memantine (MD = −5.23, 95% CrI = −8.72 to −1.56) improved behavior more than placebo. NMA found that donepezil (MD = −0.32, 95% CrI = −0.46 to −0.19), donepezil+memantine (MD = −0.57, 95% CrI = −0.95 to −0.21), oral rivastigmine (MD = −0.38, 95% CrI = −0.56 to −0.17), and galantamine (MD = −3.79, 95% CrI = −6.98 to −0.59) improved global status more than placebo. NMA found that galantamine decreased the odds of mortality (odds ratio = 0.56, 95% CrI = 0.36–0.87). No agent increased risk of serious adverse events, falls, or bradycardia. Some increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine). Conclusion An exhaustive review of the literature involving 142 studies demonstrated that cognitive enhancers in general have minimal effects on cognition according to minimal clinically important difference and global ratings. The drugs appear safe, but this must be interpreted cautiously because trial participants may have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.

Objective: Interrupted time series (ITS) designs are robust quasi-experimental designs commonly used to evaluate the impact of interventions and programs implemented in healthcare settings. This scoping review aims to 1) identify and summarize existing methods used in the analysis of ITS studies conducted in health research, 2) elucidate their strengths and limitations, 3) describe their applications in health research and 4) identify any methodological gaps and challenges. Design: Scoping review. Data Sources: Searches were conducted in MEDLINE, JSTOR, PUBMED, EMBASE, CINAHL, Web of Science and the Cochrane Library from inception until September 2017. Study Selection: Studies in health research involving ITS methods or reporting on the application of ITS designs. Data Extraction: Screening of studies was completed independently and in duplicate by two reviewers. One reviewer extracted the data from relevant studies in consultations with a second reviewer. Results of the review were presented with respect to methodological and application areas, and data were summarized using descriptive statistics. Results: A total of 1389 articles were included, of which 98.27% (N=1365) were application papers. Segmented linear regression was the most commonly used method (26%, N=360). A small percentage (1.73%, N=24) were methods papers, of which 11 described either the development of novel methods or improvement of existing methods, 7 adapted methods from other areas of statistics, while 6 provided comparative assessment of conventional ITS methods. Conclusion: A significantly increasing trend in ITS use over time is observed, where its application in health research almost tripled within the last decade. Several statistical methods are available for analyzing ITS data. Researchers should consider the types of data and validate the required assumptions for the various methods. There is a significant methodological gap in ITS analysis involving aggregated data, where analyses involving such data did not account for heterogeneity across patients and hospital settings.

BackgroundFunding agencies and research journals are increasingly demanding that researchers share their data in public repositories. Despite these requirements, researchers still withhold data, refuse to share, and deposit data that lacks annotation. We conducted a meta-synthesis to examine the views, perspectives, and experiences of academic researchers on data sharing and reuse of research data. MethodsWe searched the published and unpublished literature for studies on data sharing by researchers in academic institutions. Two independent reviewers screened citations and abstracts, then full-text articles. Data abstraction was performed independently by two investigators. The abstracted data was read and reread in order to generate codes. Key concepts were identified and thematic analysis was used for data synthesis. ResultsWe reviewed 2005 records and included 45 studies along with 3 companion reports. The studies were published between 2003 and 2018 and most were conducted in North America (60%) or Europe (17%). The four major themes that emerged were data integrity, responsible conduct of research, feasibility of sharing data, and value of sharing data. Researchers lack time, resources, and skills to effectively share their data in public repositories. Data quality is affected by this, along with subjective decisions around what is considered to be worth sharing. Deficits in infrastructure also impede the availability of research data. Incentives for sharing data are lacking. ConclusionResearchers lack skills to share data in a manner that is efficient and effective. Improved infrastructure support would allow them to make data available quickly and seamlessly. The

ObjectiveThe purpose of this study is to describe the volume, topics, and methodological nature of the existing research literature on research data management in academic institutions.Materials and methodsWe conducted a scoping review by searching forty literature databases encompassing a broad range of disciplines from inception to April 2016. We included all study types and data extracted on study design, discipline, data collection tools, and phase of the research data lifecycle.ResultsWe included 301 articles plus 10 companion reports after screening 13,002 titles and abstracts and 654 full-text articles. Most articles (85%) were published from 2010 onwards and conducted within the sciences (86%). More than three-quarters of the articles (78%) reported methods that included interviews, cross-sectional, or case studies. Most articles (68%) included the Giving Access to Data phase of the UK Data Archive Research Data Lifecycle that examines activities such as sharing data. When studies were grouped into five dominant groupings (Stakeholder, Data, Library, Tool/Device, and Publication), data quality emerged as an integral element.ConclusionMost studies relied on self-reports (interviews, surveys) or accounts from an observer (case studies) and we found few studies that collected empirical evidence on activities amongst data producers, particularly those examining the impact of research data management interventions. As well, fewer studies examined research data management at the early phases of research projects. The quality of all research outputs needs attention, from the application of best practices in research data management studies, to data producers depositing data in repositories for long-term use.

BackgroundAlthough serotonin (5-HT3) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy.MethodsWe searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted.ResultsAfter screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13–4.17).For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall.ConclusionsMost 5-HT3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.Trial registrationThis study was registered at PROSPERO: (CRD42013003564).Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0761-9) contains supplementary material, which is available to authorized users.

BackgroundSerotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients, but these agents may be harmful. We conducted a systematic review on the comparative safety of 5-HT3 receptor antagonists.MethodsSearches were done in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify studies comparing 5-HT3 receptor antagonists with each other, placebo, and/or other antiemetic agents for patients undergoing surgical procedures. Screening search results, data abstraction, and risk of bias assessment were conducted by two reviewers independently. Random-effects pairwise meta-analysis and network meta-analysis (NMA) were conducted. PROSPERO registry number: CRD42013003564.ResultsOverall, 120 studies and 27,787 patients were included after screening of 7,608 citations and 1,014 full-text articles. Significantly more patients receiving granisetron plus dexamethasone experienced an arrhythmia relative to placebo (odds ratio (OR) 2.96, 95 % confidence interval (CI) 1.11–7.94), ondansetron (OR 3.23, 95 % CI 1.17–8.95), dolasetron (OR 4.37, 95 % CI 1.51–12.62), tropisetron (OR 3.27, 95 % CI 1.02–10.43), and ondansetron plus dexamethasone (OR 5.75, 95 % CI 1.71–19.34) in a NMA including 31 randomized clinical trials (RCTs) and 6,623 patients of all ages. No statistically significant differences in delirium frequency were observed across all treatment comparisons in a NMA including 18 RCTs and 3,652 patients.ConclusionGranisetron plus dexamethasone increases the risk of arrhythmia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0379-3) contains supplementary material, which is available to authorized users.

ObjectiveTo evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM) and poor glycaemic control despite treatment with two oral agents.SettingStudies were multicentre and multinational.ParticipantsTen studies including 2967 patients with T2DM.InterventionsStudies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM.Primary and secondary outcome measuresPrimary outcome was glycosylated haemoglobin (HbA1c). Secondary outcomes were healthcare utilisation, body weight, fractures, quality of life, microvascular complications, macrovascular complications, all-cause mortality, harms, cost and cost-effectiveness.Results10 randomised clinical trials with 2967 patients were included after screening 5831 titles and abstracts, and 180 full-text articles. DPP-4 inhibitors significantly reduced HbA1c versus placebo in network meta-analysis (NMA; mean difference (MD) −0.62%, 95% CI −0.93% to −0.33%) and meta-analysis (MD −0.61%, 95% CI −0.81% to −0.41%), respectively. Significant differences in HbA1c were not observed for neutral protamine Hagedorn (NPH) insulin versus placebo and DPP-4 inhibitors versus NPH insulin in NMA. In meta-analysis, no significant differences were observed between DPP-4 inhibitors and placebo for severe hypoglycaemia, weight gain, cardiovascular disease, overall harms, treatment-related harms and mortality, although patients receiving DPP-4 inhibitors experienced less infections (relative risk 0.72, 95% CI 0.57 to 0.91).ConclusionsDPP-4 inhibitors were superior to placebo in reducing HbA1c levels in adults with T2DM taking at least two oral agents. Compared with placebo, no safety signals were detected with DPP-4 inhibitors and there was a reduced risk of infection. There was no significant difference in HbA1c observed between NPH and placebo or NPH and DPP-4 inhibitors.Trial registration numberPROSPERO # CRD42013003624.