Rapid antigen-based and rapid molecular tests for the detection of SARS-CoV-2: a rapid review with network meta-analysis of diagnostic test accuracy studies.

BACKGROUND: The global spread of COVID-19 created an explosion in rapid tests with results in < 1 hour, but their relative performance characteristics are not fully understood yet. Our aim was to determine the most sensitive and specific rapid test for the diagnosis of SARS-CoV-2. METHODS: Design: Rapid review and diagnostic test accuracy network meta-analysis (DTA-NMA). ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and observational studies assessing rapid antigen and/or rapid molecular test(s) to detect SARS-CoV-2 in participants of any age, suspected or not with SARS-CoV-2 infection. INFORMATION SOURCES: Embase, MEDLINE, and Cochrane Central Register of Controlled Trials, up to September 12, 2021. OUTCOME MEASURES: Sensitivity and specificity of rapid antigen and molecular tests suitable for detecting SARS-CoV-2. Data extraction and risk of bias assessment: Screening of literature search results was conducted by one reviewer; data abstraction was completed by one reviewer and independently verified by a second reviewer. Risk of bias was not assessed in the included studies. DATA SYNTHESIS: Random-effects meta-analysis and DTA-NMA. RESULTS: We included 93 studies (reported in 88 articles) relating to 36 rapid antigen tests in 104,961 participants and 23 rapid molecular tests in 10,449 participants. Overall, rapid antigen tests had a sensitivity of 0.75 (95% confidence interval 0.70-0.79) and specificity of 0.99 (0.98-0.99). Rapid antigen test sensitivity was higher when nasal or combined samples (e.g., combinations of nose, throat, mouth, or saliva samples) were used, but lower when nasopharyngeal samples were used, and in those classified as asymptomatic at the time of testing. Rapid molecular tests may result in fewer false negatives than rapid antigen tests (sensitivity: 0.93, 0.88-0.96; specificity: 0.98, 0.97-0.99). The tests with the highest sensitivity and specificity estimates were the Xpert Xpress rapid molecular test by Cepheid (sensitivity: 0.99, 0.83-1.00; specificity: 0.97, 0.69-1.00) among the 23 commercial rapid molecular tests and the COVID-VIRO test by AAZ-LMB (sensitivity: 0.93, 0.48-0.99; specificity: 0.98, 0.44-1.00) among the 36 rapid antigen tests we examined. CONCLUSIONS: Rapid molecular tests were associated with both high sensitivity and specificity, while rapid antigen tests were mainly associated with high specificity, according to the minimum performance requirements by WHO and Health Canada. Our rapid review was limited to English, peer-reviewed published results of commercial tests, and study risk of bias was not assessed. A full systematic review is required. REVIEW REGISTRATION: PROSPERO CRD42021289712.

Efficacy of sustained knowledge translation (KT) interventions in chronic disease management in older adults: systematic review and meta-analysis of complex interventions.

BACKGROUND: Chronic disease management (CDM) through sustained knowledge translation (KT) interventions ensures long-term, high-quality care. We assessed implementation of KT interventions for supporting CDM and their efficacy when sustained in older adults. METHODS: Design: Systematic review with meta-analysis engaging 17 knowledge users using integrated KT. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) including adults (> 65 years old) with chronic disease(s), their caregivers, health and/or policy-decision makers receiving a KT intervention to carry out a CDM intervention for at least 12 months (versus other KT interventions or usual care). INFORMATION SOURCES: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from each database's inception to March 2020. OUTCOME MEASURES: Sustainability, fidelity, adherence of KT interventions for CDM practice, quality of life (QOL) and quality of care (QOC). Data extraction, risk of bias (ROB) assessment: We screened, abstracted and appraised articles (Effective Practice and Organisation of Care ROB tool) independently and in duplicate. DATA SYNTHESIS: We performed both random-effects and fixed-effect meta-analyses and estimated mean differences (MDs) for continuous and odds ratios (ORs) for dichotomous data. RESULTS: We included 158 RCTs (973,074 participants [961,745 patients, 5540 caregivers, 5789 providers]) and 39 companion reports comprising 329 KT interventions, involving patients (43.2%), healthcare providers (20.7%) or both (10.9%). We identified 16 studies described as assessing sustainability in 8.1% interventions, 67 studies as assessing adherence in 35.6% interventions and 20 studies as assessing fidelity in 8.7% of the interventions. Most meta-analyses suggested that KT interventions improved QOL, but imprecisely (36 item Short-Form mental [SF-36 mental]: MD 1.11, 95% confidence interval [CI] [- 1.25, 3.47], 14 RCTs, 5876 participants, I2 = 96%; European QOL-5 dimensions: MD 0.01, 95% CI [- 0.01, 0.02], 15 RCTs, 6628 participants, I2 = 25%; St George's Respiratory Questionnaire: MD - 2.12, 95% CI [- 3.72, - 0.51] 44 12 RCTs, 2893 participants, I2 = 44%). KT interventions improved QOC (OR 1.55, 95% CI [1.29, 1.85], 12 RCTS, 5271 participants, I2 = 21%). CONCLUSIONS: KT intervention sustainability was infrequently defined and assessed. Sustained KT interventions have the potential to improve QOL and QOC in older adults with CDM. However, their overall efficacy remains uncertain and it varies by effect modifiers, including intervention type, chronic disease number, comorbidities, and participant age. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018084810.

Quality of Reporting on Guideline, Protocol, or Algorithm Implementation in Adult Trauma Centers: A Systematic Review.

OBJECTIVE: To appraise the quality of reporting on guideline, protocol, and algorithm implementations in adult trauma settings according to the Revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0). BACKGROUND: At present we do not know if published reports of guideline implementations in trauma settings are of sufficient quality to facilitate replication by other centers wishing to implement the same or similar guidelines. METHODS: A systematic review of the literature was conducted. Articles were identified through electronic databases and hand searching relevant trauma journals. Studies meeting inclusion criteria focused on a guideline, protocol, or algorithm that targeted adult trauma patients ≥18 years and/or trauma patient care providers, and evaluated the effectiveness of guideline, protocol, or algorithm implementation in terms of change in clinical practice or patient outcomes. Each included study was assessed in duplicate for adherence to the 18-item SQUIRE 2.0 criteria. The primary endpoint was the proportion of studies meeting at least 80% (score ≥15) of SQUIRE 2.0. RESULTS: Of 7368 screened studies, 74 met inclusion criteria. Thirty-nine percent of studies scored ≥80% on SQUIRE 2.0. Criteria that were met most frequently were abstract (93%), problem description (93%), and specific aims (89%). The lowest scores appeared in the funding (28%), context (47%), and results (54%) criteria. No study indicated using SQUIRE 2.0 as a guideline to writing the report. CONCLUSIONS: Significant opportunity exists to improve the utility of guideline implementation reports in adult trauma settings, particularly in the domains of study context and the implications of context for study outcomes.

Developing an explanatory theoretical model for engagement with a web-based mental health platform: results of a mixed methods study.

BACKGROUND: With the growing need for accessible, high-quality mental health services, especially during the COVID-19 pandemic, there has been increasing development and uptake of web-based interventions in the form of self-directed mental health platforms. The Big White Wall (BWW) is a web-based platform for people experiencing mental illness and addiction that offers a range of evidence-based self-directed treatment strategies. Drawing on existing data from a large-scale evaluation of the implementation of BWW in Ontario, Canada (which involved a pragmatic randomized controlled trail with an embedded qualitative process evaluation), we sought to investigate the influences on the extent to which people engage with BWW. METHODS: In this paper we drew on BWW trial participants' usage data (number of logins) and the qualitative data from the process evaluation that explored participants' experiences, engagement with and reactions to BWW. RESULTS: Our results showed that there were highly complex relationships between the influences that contributed to the level of engagement with BWW intervention. We found that a) how people expected to benefit from using a platform like BWW was an important indicator of their future usage, b) moderate perceived symptoms were linked with higher engagement; whereas fewer actual depressive symptoms predicted use and anxiety had a positive linear relationship with usage, and that c) usage depended on positive early experiences with the platform. CONCLUSIONS: Our findings suggest that the nature of engagement with platforms such as BWW is not easily predicted. We propose a theoretical framework for explaining the level of user engagement with BWW that might also be generalizable to other similar platforms.

Identifying and Overcoming Policy-Level Barriers to the Implementation of Digital Health Innovation: Qualitative Study.

BACKGROUND: High-level policy barriers impede widespread adoption for even the most well-positioned innovations. Most of the work in this field assumes rather than analyzes the driving forces of health innovation. Objective: The aim of this study was to explore the challenges and opportunities experienced by health system stakeholders in the implementation of digital health innovation in Ontario. OBJECTIVE: The aim of this study was to explore the challenges and opportunities experienced by health system stakeholders in the implementation of digital health innovation in Ontario. METHODS: We completed semistructured interviews with 10 members of senior leadership across key organizations that are engaged in health care-related digital health activities. Data were analyzed using qualitative description. RESULTS: A total of 6 key policy priorities emerged, including the need for (1) a system-level definition of innovation, (2) a clear overarching mission, and (3) clearly defined organizational roles. Operationally, there is a need to (4) standardize processes, (5) shift the emphasis to change management, and (6) align funding structures. CONCLUSIONS: These findings emphasize the critical role of the government in developing a vision and creating the foundation upon which innovation activities will be modeled.

A Mobile App to Improve Self-Management of Individuals With Type 2 Diabetes: Qualitative Realist Evaluation.

BACKGROUND: The increasing use of Web-based solutions for health prevention and promotion presents opportunities to improve self-management and adherence to guideline-based therapy for individuals with type 2 diabetes (T2DM). Despite promising preliminary evidence, many users stop using Web-based solutions due to the burden of data entry, hidden costs, loss of interest, and a lack of comprehensive features. Evaluations tend to focus on effectiveness or impact and fail to evaluate the nuanced variables that may interact to contribute to outcome success (or failure). OBJECTIVE: This study aimed to evaluate a Web-based solution for improving self-management in T2DM to identify key combinations of contextual variables and mechanisms of action that explain for whom the solution worked best and in what circumstances. METHODS: A qualitative realist evaluation was conducted with one-on-one, semistructured telephonic interviews completed at baseline, and again toward the end of the intervention period (3 months). Topics included participants' experiences of using the Web-based solution, barriers and facilitators of self-management, and barriers and facilitators to effective use. Transcripts were analyzed using thematic analysis strategies, after which the key themes were used to develop statements of the relationships between the key contextual factors, mechanisms of action, and impact on the primary outcome (glycated hemoglobin, HbA1c). RESULTS: Twenty-six interviews (14 baseline, 12 follow-up) were completed with 16 participants with T2DM, and the following 3 key groups emerged: the easiest fit, the best fit, and those who failed to activate. Self-efficacy and willingness to engage with the solution facilitated improvement in HbA1c, whereas competing priorities and psychosocial issues created barriers to engagement. Individuals with high baseline self-efficacy who were motivated, took ownership for their actions, and prioritized diabetes management were early and eager adopters of the app and recorded improvements in HbA1c over the intervention period. Individuals with moderate baseline self-efficacy and no competing priorities, who identified gaps in understanding of how their actions influence their health, were slow to adopt use but recorded the greatest improvements in HbA1c. The final group had low baseline self-efficacy and identified a range of psychosocial issues and competing priorities. These participants were uncertain of the benefits of using a Web-based solution to support self-management, ultimately resulting in minimal engagement and no improvement in HbA1c. CONCLUSIONS: Self-efficacy, competing priorities, previous behavior change, and beliefs about Web-based solutions interact to determine engagement and impact on the clinical outcomes. Considering the balance of these patient characteristics is likely to help health care providers identify individuals who are apt to benefit from a Web-based solution to support self-management of T2DM. Web-based solutions could be modified to incorporate the existing screening measures to identify individuals who are at risk of suboptimal adherence to inform the provision of additional support(s) as needed.

Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes.

BACKGROUND: Pregnant women with epilepsy frequently experience seizures related to pregnancy complications and are often prescribed anti-epileptic drugs (AEDs) to manage their symptoms. However, less is known about the comparative safety of AED exposure in utero. We aimed to compare the risk of congenital malformations (CMs) and prenatal outcomes of AEDs in infants/children who were exposed to AEDs in utero through a systematic review and Bayesian random-effects network meta-analysis. METHODS: MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to December 15, 2015. Two reviewers independently screened titles/abstracts and full-text papers for experimental and observational studies comparing mono- or poly-therapy AEDs versus control (no AED exposure) or other AEDs, then abstracted data and appraised the risk of bias. The primary outcome was incidence of major CMs, overall and by specific type (cardiac malformations, hypospadias, cleft lip and/or palate, club foot, inguinal hernia, and undescended testes). RESULTS: After screening 5305 titles and abstracts, 642 potentially relevant full-text articles, and 17 studies from scanning reference lists, 96 studies were eligible (n = 58,461 patients). Across all major CMs, many AEDs were associated with higher risk compared to control. For major CMs, ethosuximide (OR, 3.04; 95% CrI, 1.23-7.07), valproate (OR, 2.93; 95% CrI, 2.36-3.69), topiramate (OR, 1.90; 95% CrI, 1.17-2.97), phenobarbital (OR, 1.83; 95% CrI, 1.35-2.47), phenytoin (OR, 1.67; 95% CrI, 1.30-2.17), carbamazepine (OR, 1.37; 95% CrI, 1.10-1.71), and 11 polytherapies were significantly more harmful than control, but lamotrigine (OR, 0.96; 95% CrI, 0.72-1.25) and levetiracetam (OR, 0.72; 95% CrI, 0.43-1.16) were not. CONCLUSION: The newer generation AEDs, lamotrigine and levetiracetam, were not associated with significant increased risks of CMs compared to control, and were significantly less likely to be associated with children experiencing cardiac malformations than control. However, this does not mean that these agents are not harmful to infants/children exposed in utero. Counselling is advised concerning teratogenic risks when the prescription is written for a woman of childbearing age and before women continue with these agents when considering pregnancy, such as switching from polytherapy to monotherapy with evidence of lower risk and avoiding AEDs, such as valproate, that are consistently associated with CMs. These decisions must be balanced against the need for seizure control. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014008925.

Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis.

BACKGROUND: Although 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. METHODS: We 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. RESULTS: After 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. CONCLUSIONS: Most 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 REGISTRATION: This study was registered at PROSPERO: ( CRD42013003564 ).

A scoping review of indirect comparison methods and applications using individual patient data.

BACKGROUND: Several indirect comparison methods, including network meta-analyses (NMAs), using individual patient data (IPD) have been developed to synthesize evidence from a network of trials. Although IPD indirect comparisons are published with increasing frequency in health care literature, there is no guidance on selecting the appropriate methodology and on reporting the methods and results. METHODS: In this paper we examine the methods and reporting of indirect comparison methods using IPD. We searched MEDLINE, Embase, the Cochrane Library, and CINAHL from inception until October 2014. We included published and unpublished studies reporting a method, application, or review of indirect comparisons using IPD and at least three interventions. RESULTS: We identified 37 papers, including a total of 33 empirical networks. Of these, only 9 (27 %) IPD-NMAs reported the existence of a study protocol, whereas 3 (9 %) studies mentioned that protocols existed without providing a reference. The 33 empirical networks included 24 (73 %) IPD-NMAs and 9 (27 %) matching adjusted indirect comparisons (MAICs). Of the 21 (64 %) networks with at least one closed loop, 19 (90 %) were IPD-NMAs, 13 (68 %) of which evaluated the prerequisite consistency assumption, and only 5 (38 %) of the 13 IPD-NMAs used statistical approaches. The median number of trials included per network was 10 (IQR 4-19) (IPD-NMA: 15 [IQR 8-20]; MAIC: 2 [IQR 3-5]), and the median number of IPD trials included in a network was 3 (IQR 1-9) (IPD-NMA: 6 [IQR 2-11]; MAIC: 2 [IQR 1-2]). Half of the networks (17; 52 %) applied Bayesian hierarchical models (14 one-stage, 1 two-stage, 1 used IPD as an informative prior, 1 unclear-stage), including either IPD alone or with aggregated data (AD). Models for dichotomous and continuous outcomes were available (IPD alone or combined with AD), as were models for time-to-event data (IPD combined with AD). CONCLUSIONS: One in three indirect comparison methods modeling IPD adjusted results from different trials to estimate effects as if they had come from the same, randomized, population. Key methodological and reporting elements (e.g., evaluation of consistency, existence of study protocol) were often missing from an indirect comparison paper.

Examining semantics in interprofessional research: A bibliometric study.

While experts in the field provide clarity between terms such as interprofessional and multidisciplinary, the published literature may not be offering this preciseness. A bibliometric analysis was conducted on 1,148 studies that examined terms such as interprofessional, multidisciplinary, and teamwork in order to examine patterns of indexing, overlap in how terms and phrases are used by authors, and consistencies in the definitions of terminology. A small number of relevant indexing terms are available in PubMed but were not regularly applied to the studies in this subject area. Our findings indicate that relying on indexing terms to locate this body of literature will not reliably identify all relevant studies when searching the literature. Definitions for these terms were typically not offered by authors, references were not regularly provided when definitions were included, and clear distinctions between the different terms were not reliably provided, thus creating further difficulties. Poor indexing, lack of consistent definitions being used in the research literature, and some authors using phrases and terms as synonyms make it challenging for educators, scholars, and researchers to search, find, and use this body of literature.

Comparative efficacy of serotonin (5-HT3) receptor antagonists in patients undergoing surgery: a systematic review and network meta-analysis.

BACKGROUND: Serotonin (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. METHODS: Searches 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. RESULTS: Overall, 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. CONCLUSIONS: Granisetron plus dexamethasone was often the most effective antiemetic, with the number needed to treat ranging from two to nine.

Comparative safety of serotonin (5-HT3) receptor antagonists in patients undergoing surgery: a systematic review and network meta-analysis.

BACKGROUND: Serotonin (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. METHODS: Searches 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. RESULTS: Overall, 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. CONCLUSION: Granisetron plus dexamethasone increases the risk of arrhythmia.

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

BACKGROUND: The 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. METHODS: Utilizing 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). RESULTS: This 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. CONCLUSIONS: This 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.

Trivalent and quadrivalent seasonal influenza vaccine in adults aged 60 and older: a systematic review and network meta-analysis.

OBJECTIVES: To compare the efficacy of influenza vaccines of any valency for adults 60 years and older. DESIGN AND SETTING: Systematic review with network meta-analysis (NMA) of randomised controlled trials (RCTs). MEDLINE, EMBASE, JBI Evidence-Based Practice (EBP) Database, PsycINFO, and Cochrane Evidence -Based Medicine database were searched from inception to 20 June 20, 2022. Two reviewers screened, abstracted, and appraised articles (Cochrane Risk of Bias (ROB) 2.0 tool) independently. We assessed certainty of findings using Confidence in Network Meta-Analysis and Grading of Recommendations, Assessment, Development and Evaluations approaches. We performed random-effects meta-analysis and network meta-analysis (NMA), and estimated odds ratios (ORs) for dichotomous outcomes and incidence rate ratios (IRRs) for count outcomes along with their corresponding 95% confidence intervals (CIs) and prediction intervals. PARTICIPANTS: Older adults (≥60 years old) receiving an influenza vaccine licensed in Canada or the USA (vs placebo, no vaccine, or any other licensed vaccine), at any dose. MAIN OUTCOME MEASURES: Laboratory-confirmed influenza (LCI) and influenza-like illness (ILI). Secondary outcomes were the number of vascular adverse events, hospitalisation for acute respiratory infection (ARI) and ILI, inpatient hospitalisation, emergency room (ER) visit for ILI, outpatient visit, and mortality, among others. RESULTS: We included 41 RCTs and 15 companion reports comprising 8 vaccine types and 206 032 participants. Vaccines may prevent LCI compared with placebo, with high-dose trivalent inactivated influenza vaccine (IIV3-HD) (NMA: 9 RCTs, 52 202 participants, OR 0.23, 95% confidence interval (CI) (0.11 to 0.51), low certainty of evidence) and recombinant influenza vaccine (RIV) (OR 0.25, 95%CI (0.08 to 0.73), low certainty of evidence) among the most efficacious vaccines. Standard dose trivalent IIV3 (IIV3-SD) may prevent ILI compared with placebo, but the result was imprecise (meta-analysis: 2 RCTs, 854 participants, OR 0.39, 95%CI (0.15 to 1.02), low certainty of evidence). Any HD was associated with prevention of ILI compared with placebo (NMA: 9 RCTs, 65 658 participants, OR 0.38, 95%CI (0.15 to 0.93)). Adjuvanted quadrivalent IIV (IIV4-Adj) may be associated with the least vascular adverse events, but the results were very uncertain (NMA: eight 8 RCTs, 57 677 participants, IRR 0.18, 95%CI (0.07 to 0.43), very low certainty of evidence). RIV on all-cause mortality may be comparable to placebo (NMA: 20 RCTs, 140 577 participants, OR 1.01, 95%CI (0.23 to 4.49), low certainty of evidence). CONCLUSIONS: This systematic review demonstrated efficacy associated with IIV3-HD and RIV vaccines in protecting older persons against LCI. RIV vaccine may reduce all-cause mortality when compared with other vaccines, but the evidence is uncertain. Differences in efficacy between influenza vaccines remain uncertain with very low to moderate certainty of evidence. PROSPERO REGISTRATION NUMBER: CRD42020177357.

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

BACKGROUND: Influenza 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. METHODS: We 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%). RESULTS: We 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%). CONCLUSIONS: The 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.

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.

Safety of influenza vaccination during pregnancy: a systematic review.

OBJECTIVE: We conducted a systematic review to evaluate associations between influenza vaccination during pregnancy and adverse birth outcomes and maternal non-obstetric serious adverse events (SAEs), taking into consideration confounding and temporal biases. METHODS: Electronic databases (Ovid MEDLINE ALL, Embase Classic+Embase and the Cochrane Central Register of Controlled Trials) were searched to June 2021 for observational studies assessing associations between influenza vaccination during pregnancy and maternal non-obstetric SAEs and adverse birth outcomes, including preterm birth, spontaneous abortion, stillbirth, small-for-gestational-age birth and congenital anomalies. Studies of live attenuated vaccines, single-arm cohort studies and abstract-only publications were excluded. Records were screened using a liberal accelerated approach initially, followed by a dual independent approach for full-text screening, data extraction and risk of bias assessment. Pairwise meta-analyses were conducted, where two or more studies met methodological criteria for inclusion. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess evidence certainty. RESULTS: Of 9443 records screened, 63 studies were included. Twenty-nine studies (24 cohort and 5 case-control) evaluated seasonal influenza vaccination (trivalent and/or quadrivalent) versus no vaccination and were the focus of our prioritised syntheses; 34 studies of pandemic vaccines (2009 A/H1N1 and others), combinations of pandemic and seasonal vaccines, and seasonal versus seasonal vaccines were also reviewed. Control for confounding and temporal biases was inconsistent across studies, limiting pooling of data. Meta-analyses for preterm birth, spontaneous abortion and small-for-gestational-age birth demonstrated no significant associations with seasonal influenza vaccination. Immortal time bias was observed in a sensitivity analysis of meta-analysing risk-based preterm birth data. In descriptive summaries for stillbirth, congenital anomalies and maternal non-obstetric SAEs, no significant association with increased risk was found in any studies. All evidence was of very low certainty. CONCLUSIONS: Evidence of very low certainty suggests that seasonal influenza vaccination during pregnancy is not associated with adverse birth outcomes or maternal non-obstetric SAEs. Appropriate control of confounding and temporal biases in future studies would improve the evidence base.

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

BACKGROUND: A 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. METHODS: We 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. DISCUSSION: This 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.

Software to Conduct a Meta-Analysis and Network Meta-Analysis.

Statistical software for meta-analysis (MA) and network meta-analysis (NMA) have become indispensable for researchers. The aim of this chapter is to introduce key features of MA and NMA software to compare the effectiveness of interventions. Commonly used or routinely maintained statistical software are reviewed, including commercial and open-sourced programs such as Stata, R and Excel plug-ins. It does not provide a comprehensive overview of all features available in the software covered. Rather, it focuses on the essential features required to carry out an MA or NMA . This chapter begins with a review of key considerations when implementing an MA or NMA , then presents a summary of the software. Key features of each software option are discussed.

Understanding Engagement and the Potential Impact of an Electronic Drug Repository: Multi-Methods Study.

BACKGROUND: Centralized drug repositories can reduce adverse events and inappropriate prescriptions by enabling access to dispensed medication data at the point of care; however, how they achieve this goal is largely unknown. OBJECTIVE: This study aims to understand the perceived clinical value; the barriers to and enablers of adoption; and the clinician groups for which a provincial, centralized drug repository may provide the most benefit. METHODS: A mixed methods approach, including a web-based survey and semistructured interviews, was used. Participants were clinicians (eg, nurses, physicians, and pharmacists) in Ontario who were eligible to use the digital health drug repository (DHDR), irrespective of actual use. Survey data were ranked on a 7-point adjectival scale and analyzed using descriptive statistics, and interviews were analyzed using qualitative descriptions. RESULTS: Of the 161 survey respondents, only 40 (24.8%) actively used the DHDR. Perceptions of the utility of the DHDR were neutral (mean scores ranged from 4.11 to 4.76). Of the 75.2% (121/161) who did not use the DHDR, 97.5% (118/121) rated access to medication information (eg, dose, strength, and frequency) as important. Reasons for not using the DHDR included the cumbersome access process and the perception that available data were incomplete or inaccurate. Of the 33 interviews completed, 26 (79%) were active DHDR users. The DHDR was a satisfactory source of secondary information; however, the absence of medication instructions and prescribed medications (which were not dispensed) limited its ability to provide a comprehensive profile to meaningfully support clinical decision-making. CONCLUSIONS: Digital drug repositories must be adjusted to align with the clinician's needs to provide value. Ensuring integration with point-of-care systems, comprehensive clinical data, and streamlined onboarding processes would optimize clinically meaningful use. The electronic provision of accessible drug information to providers across health care settings has the potential to improve efficiency and reduce medication errors.