Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis.

BACKGROUND: Statins may prevent recurrent ischemic events after ischemic stroke. Determining which statin to use remains controversial. We aimed to summarize the evidence for the use of statins in secondary prevention for patients with ischemic stroke by comparing benefits and harms of various statins. METHODS: We searched for randomized controlled trials (RCTs) assessing statins in patients with ischemic stroke or transient ischemic attack (TIA) in MEDLINE, EMBASE, and CENTRAL up to July 2017. Two authors extracted data and appraised risks of bias. We performed pairwise meta-analyses and trial sequential analyses (TSA) to compare statins versus placebo/no statin, and network meta-analyses using frequentist random-effects models to compare statins through indirect evidence. We used GRADE to rate the overall certainty of evidence. Primary outcomes were all-cause mortality and all strokes. Secondary outcomes were different types of strokes, cardiovascular events, and adverse events. RESULTS: We identified nine trials (10,741 patients). No head-to-head RCTs were found. The median follow-up period was 2.5 years. Statins did not seem to modify all stroke and all-cause mortality outcomes; they were associated with a decreased risk of ischemic stroke (odds ratio, OR, 0.81 [95% CI, 0.70 to 0.93]; absolute risk difference, ARD, - 1.6% [95% CI, - 2.6 to - 0.6%]), ischemic stroke or TIA (OR, 0.75 [95% CI, 0.64 to 0.87]; ARD, - 4.2% [95% CI, - 6.2 to - 2.1%]), and cardiovascular event (OR, 0.75 [95% CI, 0.69 to 0.83]; ARD, - 5.4% [95% CI, - 6.8 to - 3.6%]), and did not seem to modify rhabdomyolysis, myalgia, or rise in creatine kinase. In the comparison of different statins, moderate- to high-quality evidence indicated that differences between pharmaceutical products seemed modest, with high doses (e.g., atorvastatin 80 mg/day and simvastatin 40 mg/day) associated with the greatest benefits. TSA excluded random error as a cause of the findings for ischemic stroke and cardiovascular event outcomes. Evidence for increased risk of hemorrhagic stroke was sensitive to the exclusion of the SPARCL trial. CONCLUSIONS: Evidence strongly suggests that statins are associated with a reduction in the absolute risk of ischemic strokes and cardiovascular events. Differences in effects among statins were modest, signaling potential therapeutic equivalence. TRIAL REGISTRATION: PROSPERO CRD42018079112.

E-learning for health professionals.

BACKGROUND: The use of e-learning, defined as any educational intervention mediated electronically via the Internet, has steadily increased among health professionals worldwide. Several studies have attempted to measure the effects of e-learning in medical practice, which has often been associated with large positive effects when compared to no intervention and with small positive effects when compared with traditional learning (without access to e-learning). However, results are not conclusive. OBJECTIVES: To assess the effects of e-learning programmes versus traditional learning in licensed health professionals for improving patient outcomes or health professionals' behaviours, skills and knowledge. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases and three trial registers up to July 2016, without any restrictions based on language or status of publication. We examined the reference lists of the included studies and other relevant reviews. If necessary, we contacted the study authors to collect additional information on studies. SELECTION CRITERIA: Randomised trials assessing the effectiveness of e-learning versus traditional learning for health professionals. We excluded non-randomised trials and trials involving undergraduate health professionals. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed risk of bias. We graded the certainty of evidence for each outcome using the GRADE approach and standardised the outcome effects using relative risks (risk ratio (RR) or odds ratio (OR)) or standardised mean difference (SMD) when possible. MAIN RESULTS: We included 16 randomised trials involving 5679 licensed health professionals (4759 mixed health professionals, 587 nurses, 300 doctors and 33 childcare health consultants).When compared with traditional learning at 12-month follow-up, low-certainty evidence suggests that e-learning may make little or no difference for the following patient outcomes: the proportion of patients with low-density lipoprotein (LDL) cholesterol of less than 100 mg/dL (adjusted difference 4.0%, 95% confidence interval (CI) -0.3 to 7.9, N = 6399 patients, 1 study) and the proportion with glycated haemoglobin level of less than 8% (adjusted difference 4.6%, 95% CI -1.5 to 9.8, 3114 patients, 1 study). At 3- to 12-month follow-up, low-certainty evidence indicates that e-learning may make little or no difference on the following behaviours in health professionals: screening for dyslipidaemia (OR 0.90, 95% CI 0.77 to 1.06, 6027 patients, 2 studies) and treatment for dyslipidaemia (OR 1.15, 95% CI 0.89 to 1.48, 5491 patients, 2 studies). It is uncertain whether e-learning improves or reduces health professionals' skills (2912 health professionals; 6 studies; very low-certainty evidence), and it may make little or no difference in health professionals' knowledge (3236 participants; 11 studies; low-certainty evidence).Due to the paucity of studies and data, we were unable to explore differences in effects across different subgroups. Owing to poor reporting, we were unable to collect sufficient information to complete a meaningful 'Risk of bias' assessment for most of the quality criteria. We evaluated the risk of bias as unclear for most studies, but we classified the largest trial as being at low risk of bias. Missing data represented a potential source of bias in several studies. AUTHORS' CONCLUSIONS: When compared to traditional learning, e-learning may make little or no difference in patient outcomes or health professionals' behaviours, skills or knowledge. Even if e-learning could be more successful than traditional learning in particular medical education settings, general claims of it as inherently more effective than traditional learning may be misleading.

What hinders the uptake of computerized decision support systems in hospitals? A qualitative study and framework for implementation.

BACKGROUND: Advanced Computerized Decision Support Systems (CDSSs) assist clinicians in their decision-making process, generating recommendations based on up-to-date scientific evidence. Although this technology has the potential to improve the quality of patient care, its mere provision does not guarantee uptake: even where CDSSs are available, clinicians often fail to adopt their recommendations. This study examines the barriers and facilitators to the uptake of an evidence-based CDSS as perceived by diverse health professionals in hospitals at different stages of CDSS adoption. METHODS: Qualitative study conducted as part of a series of randomized controlled trials of CDSSs. The sample includes two hospitals using a CDSS and two hospitals that aim to adopt a CDSS in the future. We interviewed physicians, nurses, information technology staff, and members of the boards of directors (n = 30). We used a constant comparative approach to develop a framework for guiding implementation. RESULTS: We identified six clusters of experiences of, and attitudes towards CDSSs, which we label as "positions." The six positions represent a gradient of acquisition of control over CDSSs (from low to high) and are characterized by different types of barriers to CDSS uptake. The most severe barriers (prevalent in the first positions) include clinicians' perception that the CDSSs may reduce their professional autonomy or may be used against them in the event of medical-legal controversies. Moving towards the last positions, these barriers are substituted by technical and usability problems related to the technology interface. When all barriers are overcome, CDSSs are perceived as a working tool at the service of its users, integrating clinicians' reasoning and fostering organizational learning. CONCLUSIONS: Barriers and facilitators to the use of CDSSs are dynamic and may exist prior to their introduction in clinical contexts; providing a static list of obstacles and facilitators, irrespective of the specific implementation phase and context, may not be sufficient or useful to facilitate uptake. Factors such as clinicians' attitudes towards scientific evidences and guidelines, the quality of inter-disciplinary relationships, and an organizational ethos of transparency and accountability need to be considered when exploring the readiness of a hospital to adopt CDSSs.

Effectiveness of computerized decision support systems linked to electronic health records: a systematic review and meta-analysis.

We systematically reviewed randomized controlled trials (RCTs) assessing the effectiveness of computerized decision support systems (CDSSs) featuring rule- or algorithm-based software integrated with electronic health records (EHRs) and evidence-based knowledge. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Abstracts of Reviews of Effects. Information on system design, capabilities, acquisition, implementation context, and effects on mortality, morbidity, and economic outcomes were extracted. Twenty-eight RCTs were included. CDSS use did not affect mortality (16 trials, 37395 patients; 2282 deaths; risk ratio [RR] = 0.96; 95% confidence interval [CI] = 0.85, 1.08; I(2) = 41%). A statistically significant effect was evident in the prevention of morbidity, any disease (9 RCTs; 13868 patients; RR = 0.82; 95% CI = 0.68, 0.99; I(2) = 64%), but selective outcome reporting or publication bias cannot be excluded. We observed differences for costs and health service utilization, although these were often small in magnitude. Across clinical settings, new generation CDSSs integrated with EHRs do not affect mortality and might moderately improve morbidity outcomes.

Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration.

BACKGROUND: Neovascular age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly populations of industrialised countries. Bevacizumab (Avastin®) and ranibizumab (Lucentis®) are targeted biological drugs (a monoclonal antibody) that inhibit vascular endothelial growth factor, an angiogenic cytokine that promotes vascular leakage and growth, thereby preventing its pathological angiogenesis. Ranibizumab is approved for intravitreal use to treat neovascular AMD, while bevacizumab is approved for intravenous use as a cancer therapy. However, due to the biological similarity of the two drugs, bevacizumab is widely used off-label to treat neovascular AMD. OBJECTIVES: To assess the systemic safety of intravitreal bevacizumab (brand name Avastin®; Genentech/Roche) compared with intravitreal ranibizumab (brand name Lucentis®; Novartis/Genentech) in people with neovascular AMD. Primary outcomes were death and All serious systemic adverse events (All SSAEs), the latter as a composite outcome in accordance with the International Conference on Harmonisation Good Clinical Practice. Secondary outcomes examined specific SSAEs: fatal and non-fatal myocardial infarctions, strokes, arteriothrombotic events, serious infections, and events grouped in some Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC). We assessed the safety at the longest available follow-up to a maximum of two years. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE and other online databases up to 27 March 2014. We also searched abstracts and clinical study presentations at meetings, trial registries, and contacted authors of included studies when we had questions. SELECTION CRITERIA: Randomised controlled trials (RCTs) directly comparing intravitreal bevacizumab (1.25 mg) and ranibizumab (0.5 mg) in people with neovascular AMD, regardless of publication status, drug dose, treatment regimen, or follow-up length, and whether the SSAEs of interest were reported in the trial report. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies and assessed the risk of bias for each study. Three authors independently extracted data.We conducted random-effects meta-analyses for the primary and secondary outcomes. We planned a pre-specified analysis to explore deaths and All SSAEs at the one-year follow-up. MAIN RESULTS: We included data from nine studies (3665 participants), including six published (2745 participants) and three unpublished (920 participants) RCTs, none supported by industry. Three studies excluded participants at high cardiovascular risk, increasing clinical heterogeneity among studies. The studies were well designed, and we did not downgrade the quality of the evidence for any of the outcomes due to risk of bias. Although the estimated effects of bevacizumab and ranibizumab on our outcomes were similar, we downgraded the quality of the evidence due to imprecision.At the maximum follow-up (one or two years), the estimated risk ratio (RR) of death with bevacizumab compared with ranibizumab was 1.10 (95% confidence interval (CI) 0.78 to 1.57, P value = 0.59; eight studies, 3338 participants; moderate quality evidence). Based on the event rates in the studies, this gives a risk of death with ranibizumab of 3.4% and with bevacizumab of 3.7% (95% CI 2.7% to 5.3%).For All SSAEs, the estimated RR was 1.08 (95% CI 0.90 to 1.31, P value = 0.41; nine studies, 3665 participants; low quality evidence). Based on the event rates in the studies, this gives a risk of SSAEs of 22.2% with ranibizumab and with bevacizumab of 24% (95% CI 20% to 29.1%).For the secondary outcomes, we could not detect any difference between bevacizumab and ranibizumab, with the exception of gastrointestinal disorders MedDRA SOC where there was a higher risk with bevacizumab (RR 1.82; 95% CI 1.04 to 3.19, P value = 0.04; six studies, 3190 participants).Pre-specified analyses of deaths and All SSAEs at one-year follow-up did not substantially alter the findings of our review.Fixed-effect analysis for deaths did not substantially alter the findings of our review, but fixed-effect analysis of All SSAEs showed an increased risk for bevacizumab (RR 1.12; 95% CI 1.00 to 1.26, P value = 0.04; nine studies, 3665 participants): the meta-analysis was dominated by a single study (weight = 46.9%).The available evidence was sensitive to the exclusion of CATT or unpublished results. For All SSAEs, the exclusion of CATT moved the overall estimate towards no difference (RR 1.01; 95% CI 0.82 to 1.25, P value = 0.92), while the exclusion of LUCAS yielded a larger RR, with more SSAEs in the bevacizumab group, largely driven by CATT (RR 1.19; 95% CI 1.06 to 1.34, P value = 0.004). The exclusion of all unpublished studies produced a RR of 1.12 for death (95% CI 0.78 to 1.62, P value = 0.53) and a RR of 1.21 for SSAEs (95% CI 1.06 to 1.37, P value = 0.004), indicating a higher risk of SSAEs in those assigned to bevacizumab than ranibizumab. AUTHORS' CONCLUSIONS: This systematic review of non-industry sponsored RCTs could not determine a difference between intravitreal bevacizumab and ranibizumab for deaths, All SSAEs, or specific subsets of SSAEs in the first two years of treatment, with the exception of gastrointestinal disorders. The current evidence is imprecise and might vary across levels of patient risks, but overall suggests that if a difference exists, it is likely to be small. Health policies for the utilisation of ranibizumab instead of bevacizumab as a routine intervention for neovascular AMD for reasons of systemic safety are not sustained by evidence. The main results and quality of evidence should be verified once all trials are fully published.