Charlene Soobiah

Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis

BackgroundInfluenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains.MethodsWe identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk × 100%).ResultsWe included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I2 <50%) across all meta-analyses, except for the LAIV meta-analyses among children (I2 = 79%).ConclusionsThe TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs.

What is the most appropriate knowledge synthesis method to conduct a review? Protocol for a scoping review

BackgroundA knowledge synthesis attempts to summarize all pertinent studies on a specific question, can improve the understanding of inconsistencies in diverse evidence, and can identify gaps in research evidence to define future research agendas. Knowledge synthesis activities in healthcare have largely focused on systematic reviews of interventions. However, a wider range of synthesis methods has emerged in the last decade addressing different types of questions (e.g., realist synthesis to explore mediating mechanisms and moderators of interventions). Many different knowledge synthesis methods exist in the literature across multiple disciplines, but locating these, particularly for qualitative research, present challenges. There is a need for a comprehensive manual for synthesis methods (quantitative/qualitative or mixed), outlining how these methods are related, and how to match the most appropriate knowledge synthesis method to answer a research question. The objectives of this scoping review are to: 1) conduct a systematic search of the literature for knowledge synthesis methods across multi-disciplinary fields; 2) compare and contrast the different knowledge synthesis methods; and, 3) map out the specific steps to conducting the knowledge syntheses to inform the development of a knowledge synthesis methods manual/tool.MethodsWe will search relevant electronic databases (e.g., MEDLINE, CINAHL), grey literature, and discipline-based listservs. The scoping review will consider all study designs including qualitative and quantitative methodologies (excluding economic analysis or clinical practice guideline development), and identify knowledge synthesis methods across the disciplines of health, education, sociology, and philosophy. Two reviewers will pilot-test the screening criteria and data abstraction forms, and will independently screen the literature and abstract the data. A three-step synthesis process will be used to map the literature to our objectives.DiscussionThis project represents the first attempt to broadly and systematically identify, define and classify knowledge synthesis methods (i.e., less traditional knowledge synthesis methods). We anticipate that our results will lead to an accepted taxonomy for less traditional knowledge synthesis methods, and to the development and implementation of a methods manual for these reviews which will be relevant to a wide range of knowledge users, including researchers, funders, and journal editors.

Harassment and discrimination in medical training: a systematic review and meta-analysis.

Purpose Harassment and discrimination include a wide range of behaviors that medical trainees perceive as being humiliating, hostile, or abusive. To understand the significance of such mistreatment and to explore potential preventive strategies, the authors conducted a systematic review and meta-analysis to examine the prevalence, risk factors, and sources of harassment and discrimination among medical trainees. Method In 2011, the authors identified relevant studies by searching MEDLINE and EMBASE, scanning reference lists of relevant studies, and contacting experts. They included studies that reported the prevalence, risk factors, and sources of harassment and discrimination among medical trainees. Two reviewers independently screened all articles and abstracted study and participant characteristics and study results. The authors assessed the methodological quality in individual studies using the Newcastle–Ottawa Scale. They also conducted a meta-analysis. Results The authors included 57 cross-sectional and 2 cohort studies in their review. The meta-analysis of 51 studies demonstrated that 59.4% of medical trainees had experienced at least one form of harassment or discrimination during their training (95% confidence interval [CI]: 52.0%–66.7%). Verbal harassment was the most commonly cited form of harassment (prevalence: 63.0%; 95% CI: 54.8%–71.2%). Consultants were the most commonly cited source of harassment and discrimination, followed by patients or patients’ families (34.4% and 21.9%, respectively). Conclusions This review demonstrates the surprisingly high prevalence of harassment and discrimination among medical trainees that has not declined over time. The authors recommend both drafting policies and promoting cultural change within academic institutions to prevent future abuse.

Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis

Background: Cognitive enhancers, including cholinesterase inhibitors and memantine, are used to treat dementia, but their effectiveness for mild cognitive impairment is unclear. We conducted a systematic review to examine the efficacy and safety of cognitive enhancers for mild cognitive impairment. Methods: Our eligibility criteria were studies of the effects of donepezil, rivastigmine, galantamine or memantine on mild cognitive impairment reporting cognition, function, behaviour, global status, and mortality or harms. We identified relevant material by searching electronic databases (e.g., MEDLINE, Embase), the references of included studies, trial registries and conference proceedings, and by contacting experts. Two reviewers independently screened the results of the literature search, abstracted data and appraised risk of bias using the Cochrane risk-of-bias tool. Results: We screened 15 554 titles and abstracts and 1384 full-text articles. Eight randomized clinical trials and 3 companion reports met our inclusion criteria. We found no significant effects of cognitive enhancers on cognition (Mini–Mental State Examination: 3 randomized clinical trials [RCTs], mean difference [MD] 0.14, 95% confidence interval [CI] −0.22 to 0.50; Alzheimer’s Disease Assessment Scale — cognition subscale: 3 RCTs, standardized MD −0.07, 95% CI−0.16 to 0.01]) or function (Alzheimer’s Disease Cooperative Study activities of daily living inventory: 2 RCTs, MD 0.30, 95% CI −0.26 to 0.86). Cognitive enhancers were associated with higher risks of nausea, diarrhea and vomiting than placebo. Interpretation: Cognitive enhancers did not improve cognition or function among patients with mild cognitive impairment and were associated with a greater risk of gastrointestinal harms. Our findings do not support the use of cognitive enhancers for mild cognitive impairment.

Comparative efficacy of serotonin (5-HT3

BackgroundSerotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients. We conducted a systematic review on the comparative efficacy 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 combined with 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, 450 studies and 80,410 patients were included after the screening of 7,608 citations and 1,014 full-text articles. Significantly fewer patients experienced nausea with any drug relative to placebo, except for ondansetron plus metoclopramide in a NMA including 195 RCTs and 24,230 patients. Significantly fewer patients experienced vomiting with any drug relative to placebo except for palonosetron plus dexamethasone in NMA including 238 RCTs and 12,781 patients. All agents resulted in significantly fewer patients with postoperative nausea and vomiting versus placebo in a NMA including 125 RCTs and 16,667 patients.ConclusionsGranisetron plus dexamethasone was often the most effective antiemetic, with the number needed to treat ranging from two to nine.

The impact of leadership training programs on physicians in academic medical centers: a systematic review.

Purpose To identify the impact of leadership training programs at academic medical centers (AMCs) on physicians’ knowledge, skills, attitudes, behaviors, and outcomes. Method In 2011, the authors conducted a systematic review of the literature, identifying relevant studies by searching electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register), scanning reference lists, and consulting experts. They deemed eligible any qualitative or quantitative study reporting on the implementation and evaluation of a leadership program for physicians in AMCs. Two independent reviewers conducted the review, screening studies, abstracting data, and assessing quality. Results The authors initially identified 2,310 citations. After the screening process, they had 11 articles describing 10 studies. Three were controlled before-and-after studies, four were before-and-after case series, and three were cross-sectional surveys. The authors did not conduct a meta-analysis because of the methodological heterogeneity across studies. Although all studies were at substantial risk of bias, the highest-quality ones showed that leadership training programs affected participants’ advancement in academic rank (48% versus 21%, P = .005) and hospital leadership position (30% versus 9%, P = .008) and that participants were more successful in publishing papers (3.5 per year versus 2.1 per year, P < .001) compared with nonparticipants. Conclusions The authors concluded that leadership programs have modest effects on outcomes important to AMCs. Given AMCs’ substantial investment in these programs, rigorous evaluation of their impact is essential. High-quality studies, including qualitative research, will allow the community to identify which programs are most effective.

Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis

Objective To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes. Design Systematic review and network meta-analysis. Data sources Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013. Study selection Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included. Results 39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference −0.39%, 95% confidence interval −0.59% to −0.19%; −0.26%, −0.48% to −0.03%; and −0.36%, −0.65% to −0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: −5.51 kg, −6.56 to −4.46 kg; glargine once daily versus NPH once daily: −5.14 kg, −6.07 to −4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses. Conclusions Long acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A1c. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility. Systematic review registration PROSPERO CRD42013003610.

Safety and effectiveness of dipeptidyl peptidase-4 inhibitors versus intermediate-acting insulin or placebo for patients with type 2 diabetes failing two oral antihyperglycaemic agents: a systematic review and network meta-analysis

Objective To 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. Setting Studies were multicentre and multinational. Participants Ten studies including 2967 patients with T2DM. Interventions Studies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM. Primary and secondary outcome measures Primary 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. Results 10 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). Conclusions DPP-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 number PROSPERO # CRD42013003624.

A scoping review identifies multiple emerging knowledge synthesis methods, but few studies operationalize the method

OBJECTIVES To systematically identify, define, and classify emerging knowledge synthesis methods through a scoping review. STUDY DESIGN AND SETTING MEDLINE, CINAHL, EMBASE, PsycINFO, the Cochrane Methodology Register, the Cochrane Database of Systematic Reviews, Social Sciences Abstracts, Library and Information Science Abstracts, Philosophers Index, and Education Resources Information Center were searched to identify articles reporting emerging knowledge synthesis methods across the disciplines of health, education, sociology, and philosophy. Two reviewers independently selected studies and abstracted data for each article. RESULTS In total, 409 articles reporting on 25 knowledge synthesis methods were included after screening of 17,962 titles and abstracts and 1,010 potentially relevant full-text articles. Most of the included articles were an application of the method (83.9%); only 3.7% were seminal articles that fully described the method (i.e., operationalized the steps). Most of the included articles were published after 2005. The methods were most commonly used across the fields of nursing, health care science and services, and health policy. CONCLUSION We found a lack of guidance on how to select a knowledge synthesis method. We propose convening an international group of leaders in the knowledge synthesis field to help clarify emerging approaches to knowledge synthesis.

Natural attack rate of influenza in unvaccinated children and adults: a meta-regression analysis

BackgroundThe natural (i.e. unvaccinated population) attack rate of an infectious disease is an important parameter required for understanding disease transmission. As such, it is an input parameter in infectious disease mathematical models. Influenza is an infectious disease that poses a major health concern worldwide and the natural attack rate of this disease is crucial in determining the effectiveness and cost-effectiveness of public health interventions and informing surveillance program design. We estimated age-stratified, strain-specific natural attack rates of laboratory-confirmed influenza in unvaccinated individuals.MethodsUtilizing an existing systematic review, we calculated the attack rates in the trial placebo arms using a random effects model and a meta-regression analysis (GSK study identifier: 117102).ResultsThis post-hoc analysis included 34 RCTs (Randomized Control Trials) contributing to 47 influenza seasons from 1970 to 2009. Meta-regression analyses showed that age and type of influenza were important covariates. The attack rates (95% CI (Confidence Interval)) in adults for all influenza, type A and type B were 3.50% (2.30%, 4.60%), 2.32% (1.47%, 3.17%) and 0.59% (0.28%, 0.91%) respectively. For children, they were 15.20% (11.40%, 18.90%), 12.27% (8.56%, 15.97%) and 5.50% (3.49%, 7.51%) respectively.ConclusionsThis analysis demonstrated that unvaccinated children have considerably higher exposure risk than adults and influenza A can cause more disease than influenza B. Moreover, a higher ratio of influenza B:A in children than adults was observed. This study provides a new, stratified and up to-date natural attack rates that can be used in influenza infectious disease models and are consistent with previous published work in the field.