Search

ObjectivesThe COVID-19 pandemic has stimulated growing research on treatment options. We aim to provide an overview of the characteristics of studies evaluating COVID-19 treatment.DesignRapid scoping reviewData sourcesMedline, Embase and biorxiv/medrxiv from inception to 15 May 2021.SettingHospital and community care.ParticipantsCOVID-19 patients of all ages.InterventionsCOVID-19 treatment.ResultsThe literature search identified 616 relevant primary studies of which 188 were randomised controlled trials and 299 relevant evidence syntheses. The studies and evidence syntheses were conducted in 51 and 39 countries, respectively.Most studies enrolled patients admitted to acute care hospitals (84%), included on average 169 participants, with an average age of 60 years, study duration of 28 days, number of effect outcomes of four and number of harm outcomes of one. The most common primary outcome was death (32%).The included studies evaluated 214 treatment options. The most common treatments were tocilizumab (11%), hydroxychloroquine (9%) and convalescent plasma (7%). The most common therapeutic categories were non-steroidal immunosuppressants (18%), steroids (15%) and antivirals (14%). The most common therapeutic categories involving multiple drugs were antimalarials/antibiotics (16%), steroids/non-steroidal immunosuppressants (9%) and antimalarials/antivirals/antivirals (7%). The most common treatments evaluated in systematic reviews were hydroxychloroquine (11%), remdesivir (8%), tocilizumab (7%) and steroids (7%).The evaluated treatment was in favour 50% and 36% of the evaluations, according to the conclusion of the authors of primary studies and evidence syntheses, respectively.ConclusionsThis rapid scoping review characterised a growing body of comparative-effectiveness primary studies and evidence syntheses. The results suggest future studies should focus on children, elderly ≥65 years of age, patients with mild symptoms, outpatient treatment, multimechanism therapies, harms and active comparators. The results also suggest that future living evidence synthesis and network meta-analysis would provide additional information for decision-makers on managing COVID-19.

ObjectiveTo examine the comparative efficacy and safety of cognitive enhancers by patient characteristics for managing Alzheimer’s dementia (AD).DesignSystematic review and individual patient data (IPD) network meta-analysis (NMA) based on our previously published systematic review and aggregate data NMA.Data sourcesMEDLINE, Embase, Cochrane Methodology Register, CINAHL, AgeLine and Cochrane Central Register of Controlled Trials up to March 2016.Participants80 randomised controlled trials (RCTs) including 21 138 adults with AD, and 12 RCTs with IPD including 6906 patients.InterventionsCognitive enhancers (donepezil, rivastigmine, galantamine and memantine) alone or in any combination against other cognitive enhancers or placebo.Data extraction and synthesisWe requested IPD from authors, sponsors and data sharing platforms. When IPD were not available, we used aggregate data. We appraised study quality with the Cochrane risk-of-bias. We conducted a two-stage random-effects IPD-NMA, and assessed their findings using CINeMA (Confidence in Network Meta-Analysis).Primary and secondary outcomesWe included trials assessing cognition with the Mini-Mental State Examination (MMSE), and adverse events.ResultsOur IPD-NMA compared nine treatments (including placebo). Donepezil (mean difference (MD)=1.41, 95% CI: 0.51 to 2.32) and donepezil +memantine (MD=2.57, 95% CI: 0.07 to 5.07) improved MMSE score (56 RCTs, 11 619 participants; CINeMA score: moderate) compared with placebo. According to P-score, oral rivastigmine (OR=1.26, 95% CI: 0.82 to 1.94, P-score=16%) and donepezil (OR=1.08, 95% CI: 0.87 to 1.35, P-score=30%) had the least favourable safety profile, but none of the estimated treatment effects were sufficiently precise when compared with placebo (45 RCTs, 15 649 patients; CINeMA score: moderate to high). For moderate-to-severe impairment, donepezil, memantine and their combination performed best, but for mild-to-moderate impairment donepezil and transdermal rivastigmine ranked best. Adjusting for MMSE baseline differences, oral rivastigmine and galantamine improved MMSE score, whereas when adjusting for comorbidities only oral rivastigmine was effective.ConclusionsThe choice among the different cognitive enhancers may depend on patient’s characteristics. The MDs of all cognitive enhancer regimens except for single-agent oral rivastigmine, galantamine and memantine, against placebo were clinically important for cognition (MD larger than 1.40 MMSE points), but results were quite imprecise. However, two-thirds of the published RCTs were associated with high risk of bias for incomplete outcome data, and IPD were only available for 15% of the included RCTs.PROSPERO registration numberCRD42015023507.

ObjectivesTo identify ML tools in hospital settings and how they were implemented to inform decision-making for patient care through a scoping review. We investigated the following research questions: What ML interventions have been used to inform decision-making for patient care in hospital settings? What strategies have been used to implement these ML interventions?DesignA scoping review was undertaken. MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) were searched from 2009 until June 2021. Two reviewers screened titles and abstracts, full-text articles, and charted data independently. Conflicts were resolved by another reviewer. Data were summarised descriptively using simple content analysis.SettingHospital setting.ParticipantAny type of clinician caring for any type of patient.InterventionMachine learning tools used by clinicians to inform decision-making for patient care, such as AI-based computerised decision support systems or “‘model-based’” decision support systems.Primary and secondary outcome measuresPatient and study characteristics, as well as intervention characteristics including the type of machine learning tool, implementation strategies, target population. Equity issues were examined with PROGRESS-PLUS criteria.ResultsAfter screening 17 386 citations and 3474 full-text articles, 20 unique studies and 1 companion report were included. The included articles totalled 82 656 patients and 915 clinicians. Seven studies reported gender and four studies reported PROGRESS-PLUS criteria (race, health insurance, rural/urban). Common implementation strategies for the tools were clinician reminders that integrated ML predictions (44.4%), facilitated relay of clinical information (17.8%) and staff education (15.6%). Common barriers to successful implementation of ML tools were time (11.1%) and reliability (11.1%), and common facilitators were time/efficiency (13.6%) and perceived usefulness (13.6%).ConclusionsWe found limited evidence related to the implementation of ML tools to assist clinicians with patient healthcare decisions in hospital settings. Future research should examine other approaches to integrating ML into hospital clinician decisions related to patient care, and report on PROGRESS-PLUS items.FundingCanadian Institutes of Health Research (CIHR) Foundation grant awarded to SES and the CIHR Strategy for Patient Oriented-Research Initiative (GSR-154442).Scoping review registrationhttps://osf.io/e2mna.

ObjectiveTo examine the comparative efficacy and complications of long-acting and intermediate-acting insulin for different patient characteristics for type 1 diabetes mellitus (T1DM).DesignSystematic review and individual patient data (IPD) network meta-analysis (NMA).Data sourcesMEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through June 2015.Eligibility criteriaRandomised controlled trials (RCTs) on adults with T1DM assessing glycosylated haemoglobin (A1c) and severe hypoglycaemia in long-acting and intermediate-acting insulin regimens.Data extraction and synthesisWe requested IPD from authors and funders. When IPD were not available, we used aggregate data. We conducted a random-effects model, and specifically a one-stage IPD-NMA for those studies providing IPD and a two-stage IPD-NMA to incorporate those studies not providing IPD.ResultsWe included 28 RCTs plus one companion report, after screening 6680 titles/abstracts and 205 full-text articles. Of the 28 RCTs, 27 studies provided data for the NMA with 7394 participants, of which 12 RCTs had IPD on 4943 participants. The IPD-NMA for A1c suggested that glargine once daily (mean difference [MD]=−0.31, 95% confidence interval [CI]: −0.48 to −0.14) and detemir once daily (MD=−0.25, 95% CI: –0.41 to −0.09) were superior to neutral protamine Hagedorn (NPH) once daily. NPH once/two times per day improved A1c compared with NPH once daily (MD=−0.30, 95% CI: –0.50 to −0.11). Results regarding complications in severe hypoglycaemia should be considered with great caution due to inconsistency in the evidence network. Accounting for missing data, there was no evidence of inconsistency and long-acting insulin regimens ranked higher regarding reducing severe hypoglycaemia compared with intermediate-acting insulin regimens (two-stage NMA: glargine two times per day SUCRA (Surface Under the Cumulative Ranking curve)=89%, detemir once daily SUCRA=77%; one-stage NMA: detemir once daily/two times per day SUCRA=85%). Using multiple imputations and IPD only, complications in severe hypoglycaemia increased with diabetes-related comorbidities (regression coefficient: 1.03, 95% CI: 1.02 to 1.03).ConclusionsLong-acting insulin regimens reduced A1c compared with intermediate-acting insulin regimens and were associated with lower severe hypoglycaemia. Of the observed differences, only glargine once daily achieved a clinically significant reduction of 0.30%. Results should be interpreted with caution due to very low quality of evidence.PROSPERO registration numberCRD42015023511.

BackgroundThe objective of this rapid scoping review was to identify studies of dose-sparing strategies for administration of intramuscular seasonal influenza vaccines in healthy individuals of all ages.MethodsComprehensive literature searches were executed in MEDLINE, Embase and the Cochrane library. The grey literature was searched via international clinical trial registries for relevant studies published in English in the last 20 years. We included studies in healthy humans of any age that used any dose-sparing strategy to administer intramuscular seasonal influenza vaccines. Title/abstract and full-text screening were carried out by pairs of reviewers independently. Data extraction was conducted by a single reviewer and verified by a second reviewer. Our outcomes were influenza infections, intensive care unit admission, pneumonia, hospitalisations, adverse events and mortality. Results were summarised descriptively.ResultsA total of 13 studies with 10 351 participants were included in the review and all studies were randomised controlled trials (RCTs) conducted between 2006 and 2019. The most common interventions were the trivalent influenza vaccine (n=10), followed by the quadrivalent influenza vaccine (n=4). Nine studies included infants/toddlers 6–36 months old and one of these studies also included children and adolescents. In these nine studies, no clinical effectiveness outcomes were reported. Of the four adult studies (≥18 years), two studies reported on effectiveness outcomes, however, only one RCT reported on laboratory-confirmed influenza.ConclusionsDue to the low number of studies in healthy adults and the lack of studies assessing confirmed influenza and influenza-like illness, there remains a need for further evaluation.

ObjectiveTo assess implementation and to identify barriers and facilitators to implementation, sustainability and scalability of an implementation strategy to provide lay health workers (LHWs) with the knowledge, skills and tools needed to implement an intervention to support patient tuberculosis (TB) treatment adherence.DesignMixed-methods design including a cluster randomised controlled trial and process evaluation informed by the RE-AIM framework.SettingForty-five health centres (HCs) in four districts in the south east zone of Malawi, who had an opportunity to receive cascade training.ParticipantsForty-five peer-trainers (PTs), 23 patients and 20 LHWs.InterventionImplementation strategy employing peer-led educational outreach, a clinical support tool and peer support network to implement a TB treatment adherence intervention.Outcome measuresProcess data were collected from study initiation to the end-of-study PT meeting, and included: LHW and patient interviews, quarterly PT meeting notes, training logs and study team observations and meeting notes. Data sources were first analysed in isolation, followed by method, data source and analyst triangulation. Analyses were conducted independently by two study team members, and themes revised through discussion and involvement of additional study team members as needed.ResultsForty-one HCs (91%) trained at least one LHW. Of 256 LHWs eligible to participate at study start 152 (59%) completed training, with the proportion trained per HC ranging from 0% to 100% at the end of initial cascade training. Lack of training incentives was the primary barrier to implementation, with intrinsic motivation to improve knowledge and skills, and to improve patient care and outcomes the primary facilitators of participation.ConclusionWe identified important challenges to and potential facilitators of implementation, scalability and sustainability, of the TB treatment adherence intervention. Findings provide guidance to scale-up, and use of the implementation strategies employed, to address LHW training and supervision in other areas.Trial registration numberNCT02533089.

IntroductionIn response to the burden of chronic disease among older adults, different chronic disease self-management tools have been created to optimise disease management. However, these seldom consider all aspects of disease management are not usually developed specifically for seniors or created for sustained use and are primarily focused on a single disease. We created an eHealth self-management application called ‘KeepWell’ that supports seniors with complex care needs in their homes. It incorporates the care for two or more chronic conditions from among the most prevalent high-burden chronic diseases.Methods and analysisWe will evaluate the effectiveness, cost and uptake of KeepWell in a 6-month, pragmatic, hybrid effectiveness–implementation randomised controlled trial. Older adults age ≥65 years with one or more chronic conditions who are English speaking are able to consent and have access to a computer or tablet device, internet and an email address will be eligible. All consenting participants will be randomly assigned to KeepWell or control. The allocation sequence will be determined using a random number generator.Primary outcome is perceived self-efficacy at 6 months. Secondary outcomes include quality of life, health background/status, lifestyle (nutrition, physical activity, caffeine, alcohol, smoking and bladder health), social engagement and connections, eHealth literacy; all collected via a Health Risk Questionnaire embedded within KeepWell (intervention) or a survey platform (control). Implementation outcomes will include reach, effectiveness, adoption, fidelity, implementation cost and sustainability.Ethics and disseminationEthics approval has been received from the North York General Hospital Research and Ethics Board. The study is funded by the Canadian Institutes of Health Research and the Ontario Ministry of Health. We will work with our team to develop a dissemination strategy which will include publications, presentations, plain language summaries and an end-of-grant meeting.Trial registration numberNCT04437238.

ObjectiveThe COVID-19 pandemic has highlighted ongoing challenges to optimal supportive end-of-life care for adults living in long-term care (LTC) facilities. A supportive end-of-life care approach emphasises family involvement, optimal symptom control, multidisciplinary team collaboration and death and bereavement support services for residents and families. Community-based and palliative care specialist physicians who visit residents in LTC facilities play an important role in supportive end-of-life care. Yet, perspectives, experiences and perceptions of these physicians remain unknown. The objective of this study was to explore barriers and facilitators to optimal supportive end-of-life palliative care in LTC through the experiences and perceptions of community-based and palliative specialist physicians who visit LTC facilities.DesignQualitative study using semi-structured interviews, basic qualitative description and directed content analysis using the COM-B (capability, opportunity, motivation - behaviour) theoretical framework.SettingResidential long-term care.Participants23 physicians who visit LTC facilities from across Alberta, Canada, including both in urban and rural settings of whom 18 were community-based physicians and 5 were specialist palliative care physicians.ResultsMotivation barriers include families’ lack of frailty knowledge, unrealistic expectations and emotional reactions to grief and uncertainty. Capability barriers include lack of symptom assessment tools, as well as palliative care knowledge, training and mentorship. Physical and social design barriers include lack of dedicated spaces for death and bereavement, inadequate staff, and mental health and spiritual services of insufficient scope for the population.ConclusionFindings reveal that validating families’ concerns, having appropriate symptom assessment tools, providing mentorship in palliative care and adapting the physical and social environment to support dying and grieving with dignity facilitates supportive, end-of-life care within LTC.

Introduction End-of-life care is an essential task performed by most healthcare providers and often involves decision-making about how and where patients want to receive care. To provide decision support to healthcare professionals and patients in this difficult situation, we will systematically review a knowledge cluster of the end-of-life care preferences of older patients with multimorbidity that we previously identified using an evidence map. Methods and analysis We will systematically search for studies reporting end-of-life care preferences of older patients (mean age ≥60) with multimorbidity (≥2 chronic conditions) in MEDLINE, CINAHL, PsycINFO, Social Sciences Citation Index, Social Sciences Citation Index Expanded, PSYNDEX and The Cochrane Library from inception to September 2019. We will include all primary studies that use quantitative, qualitative and mixed methodologies, irrespective of publication date and language. Two independent reviewers will assess eligibility, extract data and describe evidence in terms of study/population characteristics, preference assessment method and end-of-life care elements that matter to patients (eg, life-sustaining treatments). Risk of bias/applicability of results will be independently assessed by two reviewers using the Mixed-Methods Appraisal Tool. Using a convergent integrated approach on qualitative/quantitative studies, we will synthesise information narratively and, wherever possible, quantitatively. Ethics and dissemination Due to the nature of the proposed systematic review, ethics approval is not required. Results from our research will be disseminated at relevant (inter-)national conferences and via publication in peer-reviewed journals. Synthesising evidence on end-of-life care preferences of older patients with multimorbidity will improve shared decision-making and satisfaction in this final period of life. PROSPERO registration number CRD42020151862.

IntroductionWhile the number of women entering medical school now equals or surpasses the number of men, gender equity in medicine has not been achieved. Women continue to be under-represented in leadership roles (eg, deans, medical chairs) and senior faculty positions. In addition, women do not enter medical specialties as often as men, which can have important implications for work environment, reimbursement and the delivery of patient care. Compared with other medical specialties (eg, anaesthesiology, dermatology, etc), critical care medicine is a medical specialty with some of the lowest representation of women. While strategies to improve gender equity in critical care medicine exist in the published literature, efforts to comprehensively synthesise, prioritise and implement solutions have been limited.The objective of this programme of work is to establish priorities for the development and implementation of key strategies to improve the outcomes, well-being and experiences of women in critical care in Canada.Methods and analysisThree phases encompass this programme of work. In phase I, we will catalogue published strategies focused on improving gender inequity across medical specialties through a scoping review. In phase II, we will conduct a modified Delphi consensus process with decision-makers, physicians and researchers to identify key strategies (identified in phase I and proposed by participants in phase II) for improving gender inequity in the specialty of critical care medicine. Finally, in phase III, we will conduct a 1-day stakeholder meeting that engages participants from phase II to build capacity for the development and implementation of top ranked strategies. Data analyses from this programme of work will be both quantitative and qualitative.Ethics and disseminationThe proposed programme of work is a foundational step towards establishing targeted strategies to improve gender inequity in the medical specialty of critical care medicine. Strategies will be prioritised by stakeholders, mapped to preidentified drivers of gender equity in the specialty and be scalable to institutional needs. A final report of our results including the list of top prioritised strategies and implementation objectives will be disseminated to panel participants, critical care leadership teams and major critical care societies who are partners in this work, around the country to facilitate uptake at the local level.The University of Calgary Conjoint Health Research Ethics Board has approved this study (REB16-0890).

IntroductionDischarge communication is an important aspect of patient care but frequently has shortcomings in emergency departments (EDs). In a paediatric context, youth or parents with young children often leave the ED with minimal opportunity to ask questions or to ensure comprehension of important information. Strategies for improving discharge communication have primarily targeted patients and/or parents, although neither group has been engaged in intervention design or implementation. Furthermore, ED healthcare providers (HCPs), important actors in discharge communication practice, are rarely consulted regarding intervention design decisions. We will generate evidence to enhance discharge communication by engaging youth, parents and HCPs in the codesign of ED discharge communication strategies (EDUCATE) for asthma and minor head injury.Methods and analysisThis mixed methods study will take place at two academic paediatric EDs in Canada. The study will occur in two phases: (A) codesign and refinement of the intervention prototypes; and (B) usability testing of the prototypes. During the first phase, two codesign teams (one for each condition) will follow a series of structured design meetings based on the Behavior Change Wheel to develop the EDUCATE interventions. Each codesign team (composed of youth, parents, HCPs and study researchers) will collaborate to identify priority target behaviours and acceptable components to include in the interventions. During the second phase, we will conduct usability testing in two EDs with a group of youth, parents and HCPs to refine the interventions. Two cycles of usability testing will be conducted with intervention refinement occurring at the end of each cycle.Ethics and disseminationInformed consent will be obtained from all participants. Ethics approval for this study has been obtained from the Research Ethics Board, IWK Health Centre. Results from this study will form the basis of a future effectiveness implementation trial. Key findings will be presented at national and international conferences and published within peer-reviewed journals.

IntroductionFlexible visitation policies in hospitals are an important component of care that contributes to reduced stress and increased satisfaction among patients and their family members. Early evidence suggests restricted visitation policies enacted in hospitals during the COVID-19 pandemic are having unintended consequences on patients, family members and healthcare providers. There is a need for a comprehensive summary of the impacts of restricted visitation policies on key stakeholders and approaches to mitigate that impact.Methods and analysisWe will conduct a scoping review as per the Arksey-O’Malley 5-stage scoping review method and the Scoping Review Methods Manual by the Joanna Briggs Institute. We will search relevant electronic databases (eg, CINAHL, MEDLINE, PsycINFO), grey literature and preprint repositories. We will include all study designs including qualitative and quantitative methodologies (excluding protocols) as well as reports, opinions and editorials, to identify the broad impact of restricted hospital visitation policies due to the COVID-19 pandemic on patients, family members or healthcare providers of hospitalised patients, and approaches taken or proposed to mitigate this impact. Two reviewers will calibrate the screening criteria and data abstraction form and will independently screen studies and abstract the data. Narrative synthesis with thematic analysis will be performed.Ethics and disseminationEthical approval is not applicable as this review will be conducted on published literature only. This scoping review will identify, describe and categorise impacts of restricted hospital visitation policies due to the COVID-19 pandemic on patients, family members and healthcare providers of hospitalised patients, and approaches that have been taken to mitigate impact. We will provide a comprehensive synthesis by developing a framework of restricted visitation policies and associated impacts. Our results will inform the development of consensus statements on restricted visitation policies to be implemented in future pandemics.PROSPERO registration numberCRD42020221662.

IntroductionIn the context of the opioid crisis in North America, the benefits of evidence-based opioid agonist treatments such as buprenorphine/naloxone have not been optimised due to low uptake. Numerous factors contribute to the underuse of buprenorphine, and theory-informed approaches to identify and address implementation barriers and facilitators are needed. This scoping review aims to characterise the barriers and facilitators at the patient, healthcare professional, organisation and system level according to the Theoretical Domains Framework (TDF), and identify gaps to inform practice and policy.Methods and analysisWe will conduct a scoping review using established methods and follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. We will identify English and French-language peer-reviewed literature by searching five electronic bibliographic databases (MEDLINE, Embase, PsychINFO, CINAHL, and SocINDEX), from inception and use Google, websites of key organisations, and two or more custom search engines to identify relevant grey literature. Eligible records will be quantitative or qualitative studies that examine barriers and facilitators to buprenorphine use at the patient, healthcare professional, organisation and system level, and involve participants with diagnosis of opioid use disorder or professionals involved in their care. Two reviewers will be involved in independently screening, reviewing and charting the data and calibration exercises will be conducted at each stage. We will conduct descriptive analysis for the charted data, and deductively code barriers and facilitators using the TDF.Ethics and disseminationAs a scoping review of the literature, this study does not require ethics approval. Our dissemination strategy will focus on developing tailored activities to meet the needs of diverse knowledge user audiences. Barriers and facilitators mapped to the TDF can be linked to evidence-based strategies for change to improve buprenorphine use and access, and enable practice to reduce opioid-related harms.

Introduction Interaction of conditions and treatments, complicated care needs and substantial treatment burden make patient–physician encounters involving multimorbid older patients highly complex. To optimally integrate patients’ preferences, define and prioritise realistic treatment goals and individualise care, a patient-centred approach is recommended. However, the preferences of older patients, who are especially vulnerable and frequently multimorbid, have not been systematically investigated with regard to their health status. The purpose of this evidence map is to explore current research addressing health-related preferences of older patients with multimorbidity, and to identify the knowledge clusters and research gaps. Methods and analysis To identify relevant research, we will conduct searches in the electronic databases MEDLINE, EMBASE, PsycINFO, PSYNDEX, CINAHL, Social Science Citation Index, Social Science Citation Index Expanded and the Cochrane library from their inception. We will check reference lists of relevant articles and carry out cited reference research (forward citation tracking). Two independent reviewers will screen titles and abstracts, check full texts for eligibility and extract the data. Any disagreement will be resolved and consensus reached with the help of a third reviewer. We will include both qualitative and quantitative studies, and address preferences from the patients’ perspectives in a multimorbid population of 60 years or older. There will be no restrictions on the publication language. Data extraction tables will present study and patient characteristics, aim of study, methods used to identify preferences and outcomes (ie, type of preferences). We will summarise the data using tables and figures (ie, bubble plot) to present the research landscape and to describe clusters and gaps. Ethics and dissemination Due to the nature of the proposed evidence map, ethics approval will not be required. Results from our research will be disseminated by means of specifically prepared materials for patients, at relevant (inter)national conferences and via publication in peer-reviewed journals.

ObjectiveThis review was conducted to identify interventions effective in improving uptake and retention of HIV-positive mothers and their infants in prevention of mother to child transmission (PMTCT) services in low-income and middle-income countries (LMICs) in order to inform programme planning.MethodsWe conducted a systematic review of studies comparing usual care with any intervention to improve uptake and retention of HIV-positive pregnant or breastfeeding women and their children from birth to 2 years of age in PMTCT services in LMICs. Twenty-two electronic databases were searched from inception to 15 January 2018, for randomised, quasi-randomised and non-randomised controlled trials, and interrupted time series studies; reference lists of included articles were searched for relevant articles. Risk of bias was assessed using the Cochrane Effective Practice and Organisation of Care group criteria. Random-effects meta-analysis was conducted for studies reporting similar interventions and outcomes.ResultsWe identified 29 837 articles, of which 18 studies were included in our review. Because of heterogeneity in interventions and outcome measures, only one meta-analysis of two studies and one outcome was conducted; we found a statistically significant increase in antiretroviral therapy (ART) use during pregnancy for integration of HIV and antenatal care relative to standard non-integrated care (pooled AOR=2.69; 95% CI 1.25 to 5.78, p=0.0113). The remaining studies assessing other patient, provider or health system interventions were synthesised narratively, with small effects seen across intervention categories for both maternal and infant PMTCT outcomes based predominately on evidence with moderate to high risk of bias.ConclusionsEvidence on the effectiveness of interventions to improve uptake and retention of mothers and infants in PMTCT care is lacking. Our findings suggest that integration of HIV and antenatal care may improve ART use during pregnancy. Future studies to replicate promising approaches are needed. Improved reporting of key methodological criteria will facilitate interpretation of findings and improve the utility of evidence to PMTCT programme planners.PROSPERO registration numberCRD42015020829.

ObjectiveTo conduct a systematic review investigating the normal age-related changes in lung function in adults without known lung disease.DesignSystematic review.Data sourcesMEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched for eligible studies from inception to February 12, 2019, supplemented by manual searches of reference lists and clinical trial registries.Eligibility criteriaWe planned to include prospective cohort studies and randomised controlled trials (control arms) that measured changes in lung function over time in asymptomatic adults without known respiratory disease.Data extraction and synthesisTwo authors independently determined the eligibility of studies, extracted data and assessed the risk of bias of included studies using the modified Newcastle–Ottawa Scale.ResultsFrom 4385 records screened, we identified 16 cohort studies with 31 099 participants. All included studies demonstrated decline in lung function—forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) with age. In studies with longer follow-up (>10 years), rates of FEV1decline ranged from 17.7 to 46.4 mL/year (median 22.4 mL/year). Overall, men had faster absolute rates of decline (median 43.5 mL/year) compared with women (median 30.5 mL/year). Differences in relative FEV1change, however, were not observed between men and women. FEV1/FVC change was reported in only one study, declining by 0.29% per year. An age-specific analysis suggested the rate of FEV1function decline may accelerate with each decade of age.ConclusionsLung function—FEV1, FVC and PEFR—decline with age in individuals without known lung disease. The definition of chronic airway disease may need to be reconsidered to allow for normal ageing and ensure that people likely to benefit from interventions are identified rather than healthy people who may be harmed by potential overdiagnosis and overtreatment. The first step would be to apply age, sex and ethnicity-adjusted FEV1/FVC thresholds to the disease definition of chronic obstructive pulmonary disease.PROSPERO registration numberCRD42018087066.

ObjectiveTo assess the proportion of women who presented research or medical grand rounds at five major academic hospitals in Canada.DesignA cross-sectional study.SettingFive major university-affiliated hospitals in Toronto and Calgary.ResultsOverall, at all sites and types of academic rounds, there were an average of 17% fewer women presenting than men (PConclusionOur study demonstrated a lower proportion of females in an important outlet for academic recognition and role modelling. This provides a possible contributing factor to the under-representation of women in academic medicine and an area that can be systematically targeted to promote equity.

Objectives Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. Design and setting Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers. Participants 29 cohort studies including 5100 infants/children. Interventions Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group. Primary and secondary outcome measures Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes. Results The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control. Conclusions Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen. Trial registration number PROSPERO database (CRD42014008925).

Introduction Well-conducted randomised controlled trials (RCTs) provide the least biased estimates of intervention effects. However, RCTs are costly and time-consuming to perform and long-term follow-up of participants may be hampered by lost contacts and financial constraints. Advances in computing and population-based registries have created new possibilities for increasing the value of RCTs by post-trial extension using linkage to routinely collected administrative/registry data in order to determine long-term interventional effects. There have been recent important examples, including 20+ years follow-up studies of trials of pravastatin and mammography. Despite the potential value of post-trial extension, there has been no systematic study of this literature. This scoping review aims to characterise published post-trial extension studies, assess their value, and identify any potential challenges associated with this approach. Methods and analysis This review will use the recommended methods for scoping reviews. We will search MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A draft search strategy is included in this protocol. Review of titles and abstracts, full texts of potentially eligible studies and data/information extraction will be conducted independently by pairs of investigators. Eligible studies will be RCTs that investigated healthcare interventions that were extended by individual linkage to administrative/registry/electronic medical records data after the completion of the planned follow-up period. Information concerning the original trial, characteristics of the extension study, any clinical, policy or ethical implications and methodological or practical challenges will be collected using standardised forms. Ethics and dissemination As this study uses secondary data, and does not include person-level data, ethics approval is not required. We aim to disseminate these findings through journals and conferences targeting triallists and researchers involved in health data linkage. We aim to produce guidance for investigators on the conduct of post-trial extensions using routinely collected data.

ObjectiveTo determine (i) the difference in the frequency of serious adverse events (SAEs) reported in trial registrations and their respective primary publications and (ii) the effect of adding SAE data from registries to a network meta-analysis (NMA) in changing the surface under the cumulative ranking (SUCRA) curve values of interventions.DesignSecondary analysis of primary publications from two NMAs.Eligibility criteria for selecting studiesWe included randomised trials published in English after 2005 that were included in two NMAs of pharmacological interventions for Alzheimer’s disease and chronic obstructive pulmonary disease.Data extractionTwo reviewers independently searched multiple international trial registries for registration status and abstracted data from the included study publications and ClinicalTrials.gov.ResultsOf the 203 randomised trials included, 140 (69.0%) were registered with a trial registry and 72 (35.5%) posted results in the registry. The proportion of registered trials increased over time (38.5% in 2005 vs 78.6% in 2014). Of the publications with results posted in a trial registry, 14 (19.4%) had inconsistent reporting of overall SAEs; 7 (10.4%) studies did not report SAEs in the publication but did in the registry. In the 134 randomised trials with a prespecified primary outcome in the registry, 19 studies (9.4%) had a change in the primary outcome in the publication. Adding SAEs reported in registries to the NMAs did not affect the ranking of interventions.ConclusionWe identified inconsistent reporting of SAEs in randomised trials that were included in two NMAs. Findings highlight the importance of including trial registries in the grey literature search and verifying safety data before incorporating it into NMAs.Study registrationosf.io/mk6dr.

ObjectiveTo provide a framework for quantifying the robustness of treatment ranks based on Surface Under the Cumulative RAnking curve (SUCRA) in network meta-analysis (NMA) and investigating potential factors associated with lack of robustness.MethodsWe propose the use of Cohen’s kappa to quantify the agreement between SUCRA-based treatment ranks estimated through NMA of a complete data set and a subset of it. We illustrate our approach using five published NMA data sets, where robustness was assessed by removing studies one at a time.ResultsOverall, SUCRA-based treatment ranks were robust to individual studies in the five data sets we considered. We observed more incidences of disagreement between ranks in the networks with larger numbers of treatments. Most treatments moved only one or two ranks up or down. The lowest quadratic weighted kappa estimate observed across all networks was in the network with the smallest number of treatments (4), where weighted kappa=40%. In the network with the largest number of treatments (12), the lowest observed quadratic weighted kappa=89%, reflecting a small shift in this network's treatment ranks overall. Preliminary observations suggest that a study’s size, the number of studies making a treatment comparison, and the agreement of a study’s estimated treatment effect(s) with those estimated by other studies making the same comparison(s) may explain the overall robustness of treatment ranks to studies.ConclusionsInvestigating robustness or sensitivity in an NMA may reveal outlying rank changes that are clinically or policy-relevant. Cohen’s kappa is a useful measure that permits investigation into study characteristics that may explain varying sensitivity to individual studies. However, this study presents a framework as a proof of concept and further investigation is required to identify potential factors associated with the robustness of treatment ranks using more extensive empirical evaluations.

ObjectivesTo understand how and why effective multi-chronic disease management interventions influence health outcomes in older adults 65 years of age or older.DesignA realist review.Data sourcesElectronic databases including Medline and Embase (inception to December 2017); and the grey literature.Eligibility criteria for selecting studiesWe considered any studies (ie, experimental quasi-experimental, observational, qualitative and mixed-methods studies) as long as they provided data to explain our programme theories and effectiveness review (published elsewhere) findings. The population of interest was older adults (age ≥65 years) with two or more chronic conditions.AnalysisWe used the Realist And MEta-narrative Evidence Syntheses: Evolving Standards (RAMESES) quality and publication criteria for our synthesis aimed at refining our programme theories such that they contained multiple context-mechanism-outcome configurations describing the ways different mechanisms fire to generate outcomes. We created a 3-step synthesis process grounded in meta-ethnography to separate units of data from articles, and to derive explanatory statements across them.Results106 articles contributed to the analysis. We refined our programme theories to explain multimorbidity management in older adults: (1) care coordination interventions with the best potential for impact are team-based strategies, disease management programmes and case management; (2) optimised disease prioritisation involves ensuring that clinician work with patients to identify what symptoms are problematic and why, and to explore options that are acceptable to both clinicians and patients and (3) optimised patient self-management is dependent on patients’ capacity for selfcare and to what extent, and establishing what patients need to enable selfcare.ConclusionsTo optimise care, both clinical management and patient self-management need to be considered from multiple perspectives (patient, provider and system). To mitigate the complexities of multimorbidity management, patients focus on reducing symptoms and preserving quality of life while providers focus on the condition that most threaten morbidity and mortality.PROSPERO registration numberCRD42014014489.

Introduction Adverse events associated with medications are under-reported in postmarketing surveillance systems. A systematic review of published data from 37 studies worldwide (including Canada) found the median under-reporting rate of adverse events to be 94% in spontaneous reporting systems. This scoping review aims to assess the utility of social media and crowd-sourced data to detect and monitor adverse events related to health products including pharmaceuticals, medical devices, biologics and natural health products. Methods and analysis Our review conduct will follow the Joanna Briggs Institute scoping review methods manual. Literature searches were conducted in MEDLINE, EMBASE and the Cochrane Library from inception to 13 May 2016. Additional sources included searches of study registries, conference abstracts, dissertations, as well as websites of international regulatory authorities (eg, Food and Drug Administration (FDA), the WHO, European Medicines Agency). Search results will be supplemented by scanning the references of relevant reviews. We will include all publication types including published articles, editorials, websites and book sections that describe use of social media and crowd-sourced data for surveillance of adverse events associated with health products. Two reviewers will perform study selection and data abstraction independently, and discrepancies will be resolved through discussion. Data analysis will involve quantitative (eg, frequencies) and qualitative (eg, content analysis) methods. Dissemination The summary of results will be sent to Health Canada, who commissioned the review, and other relevant policymakers involved with the Drug Safety and Effectiveness Network. We will compile and circulate a 1-page policy brief and host a 1-day stakeholder meeting to discuss the implications, key messages and finalise the knowledge translation strategy. Findings from this review will ultimately inform the design and development of a data analytics platform for social media and crowd-sourced data for pharmacovigilance in Canada and internationally. Registration details Our protocol was registered prospectively with the Open Science Framework (https://osf.io/kv9hu/).

Introduction Engaging policymakers, healthcare managers and policy analysts in the conduct of knowledge synthesis can help increase its impact. This is particularly important for knowledge synthesis studies commissioned by decision-makers with limited timelines, as well as reviews of health policy and systems research. A scoping review will be conducted to assess barriers, facilitators, strategies and outcomes of engaging these individuals in the knowledge synthesis process. Methods and analysis We will follow the Joanna Briggs Institute guidance for scoping reviews. Literature searches of electronic databases (eg, MEDLINE, EMBASE, Cochrane Library, ERIC, PsycINFO) will be conducted from inception onwards. The electronic search will be supplemented by searching for sources that index unpublished/difficult to locate studies (eg, GreyNet International database), as well as through scanning of reference lists of reviews on related topics. All study designs using either qualitative or quantitative methodologies will be eligible if there is a description of the strategies, barriers or facilitators, and outcomes of engaging policymakers, healthcare managers and policy analysts in the knowledge synthesis process. Screening and data abstraction will be conducted by 2 team members independently after a calibration exercise across the team. A third team member will resolve all discrepancies. We will conduct frequency analysis and thematic analysis to chart and characterise the literature, identifying data gaps and opportunities for future research, as well as implications for policy. Ethics and dissemination This project was commissioned by the Alliance for Health Policy and Systems Research, WHO. The results will be used by Alliance Review Centers of health policy and systems research in low-income and middle-income countries that are conducting knowledge synthesis to inform health policymaking and decision-making. Our results will also be disseminated through conference presentations, train-the-trainer events, peer-reviewed publication and a 1-page policy brief that will be posted on the authors9 websites.

ObjectivesCare gaps in asthma may be highly prevalent but are poorly characterised. We sought to prospectively measure adherence to key evidence-based adult asthma practices in primary care, and predictors of these behaviours.DesignOne-year prospective cohort study employing an electronic chart audit.SettingThree family health teams (two academic, one community-based) in Ontario, Canada.Participants884 patients (72.1% female; 46.0±17.5 years old) (4199 total visits; 4.8±4.8 visits/patient) assigned to 23 physicians (65% female; practising for 10.0±8.6 years).Main outcome measuresThe primary outcome was the proportion of visits during which practitioners assessed asthma control according to symptom-based criteria. Secondary outcomes included the proportion of: patients who had asthma control assessed at least once; visits during which a controller medication was initiated or escalated; and patients who received a written asthma action plan. Behavioural predictors were established a priori and tested in a multivariable model.ResultsPrimary outcome: Providers assessed asthma control in 4.9% of visits and 15.4% of patients. Factors influencing assessment included clinic site (p=0.019) and presenting symptom, with providers assessing control more often during visits for asthma symptoms (35.0%) or any respiratory symptoms (18.8%) relative to other visits (1.6%) (pConclusionsMajor gaps in evidence-based asthma practice exist in primary care. Targeted knowledge translation interventions are required to address these gaps, and can be tailored by leveraging the identified behavioural predictors.Trial registration numberNCT01070095; Pre-results.

ObjectivesThis review was commissioned by WHO, South Africa-Country office because of an exponential increase in medical litigation claims related to patient safety in obstetrical care in the country. A rapid review was conducted to examine the effectiveness of quality improvement (QI) strategies on maternal and newborn patient safety outcomes, risk of litigation and burden of associated costs.DesignA rapid review of the literature was conducted to provide decision-makers with timely evidence. Medical and legal databases (eg, MEDLINE, Embase, LexisNexis Academic, etc) and reference lists of relevant studies were searched. Two reviewers independently performed study selection, abstracted data and appraised risk of bias. Results were summarised narratively.InterventionsWe included randomised clinical trials (RCTs) of QI strategies targeting health systems (eg, team changes) and healthcare providers (eg, clinician education) to improve the safety of women and their newborns. Eligible studies were limited to trials published in English between 2004 and 2015.Primary and secondary outcome measuresRCTs reporting on patient safety outcomes (eg, stillbirths, mortality and caesarean sections), litigation claims and associated costs were included.ResultsThe search yielded 4793 citations, of which 10 RCTs met our eligibility criteria and provided information on over 500 000 participants. The results are presented by QI strategy, which varied from one study to another. Studies including provider education alone (one RCT), provider education in combination with audit and feedback (two RCTs) or clinician reminders (one RCT), as well as provider education with patient education and audit and feedback (one RCT), reported some improvements to patient safety outcomes. None of the studies reported on litigation claims or the associated costs.ConclusionsOur results suggest that provider education and other QI strategy combinations targeting healthcare providers may improve the safety of women and their newborns during childbirth.

ObjectiveTo systematically identify and describe self-management interventions for adult patients with chronic kidney disease (CKD).SettingCommunity-based.ParticipantsAdults with CKD stages 1–5 (not requiring kidney replacement therapy).InterventionsSelf-management strategies for adults with CKD.Primary and secondary outcome measuresUsing a scoping review, electronic databases and grey literature were searched in October 2016 to identify self-management interventions for adults with CKD stages 1–5 (not requiring kidney replacement therapy). Randomised controlled trials (RCTs), non-RCTs, qualitative and mixed method studies were included and study selection and data extraction were independently performed by two reviewers. Outcomes included behaviours, cognitions, physiological measures, symptoms, health status and healthcare.ResultsFifty studies (19 RCTs, 7 quasi-experimental, 5 observational, 13 pre-post intervention, 1 mixed method and 5 qualitative) reporting 45 interventions were included. The most common intervention topic was diet/nutrition and interventions were regularly delivered face to face. Interventions were administered by a variety of providers, with nursing professionals the most common health professional group. Cognitions (ie, changes in general CKD knowledge, perceived self-management and motivation) were the most frequently reported outcome domain that showed improvement. Less than 1% of the interventions were co-developed with patients and 20% were based on a theory or framework.ConclusionsThere was a wide range of self-management interventions with considerable variability in outcomes for adults with CKD. Major gaps in the literature include lack of patient engagement in the design of the interventions, with the majority of interventions not applying a behavioural change theory to inform their development. This work highlights the need to involve patients to co-developed and evaluate a self-management intervention based on sound theories and clinical evidence.

Introduction The choice of a basal insulin regimen to manage type 1 diabetes mellitus (T1DM) may have different risks of adverse events and effectiveness, due to the difference in the effectiveness of these agents across patient characteristics (eg, baseline glycosylated haemoglobin; A1C). Currently, there is a lack of high quality evidence to support the tailoring of insulin regimens according to an individual9s needs. The aim of this study is to update our previous systematic review and perform an individual patient data network meta-analysis (IPD-NMA) to evaluate the comparative safety and effectiveness of long-acting versus intermediate-acting insulin in different subgroups of patients with T1DM. Methods and analysis We will update our previous literature search from January 2013 onwards searching relevant electronic databases (eg, MEDLINE), as well as perform grey literature search through relevant society/association websites, and conference abstracts, and scan reference lists of the eligible studies. We will include randomised clinical trials of any duration examining long-acting versus intermediate-acting insulin preparations for adult patients with T1DM. We will focus on A1C and severe hypoglycaemia outcomes. For each pairwise treatment comparison, we will combine all IPD from all studies in a single multilevel model, where each study is a different cluster. For a connected network of trials, we will perform an IPD-NMA to identify potential effect modifiers, and estimate the most effective and safe treatments for patients with different characteristics. If we are not successful in obtaining IPD for at least one study, we will include aggregated data (AD) abstracted from the included RCTs in our analysis, combining IPD and AD into a single model. We will report our results using the PRISMA-IPD statement. Ethics and dissemination The results of this systematic review and IPD-NMA will be of interest to stakeholders and will help in improving existing guideline recommendations. PROSPERO registry number CRD42015023511.

Objective To compare the safety and effectiveness of long-acting β-antagonists (LABA), long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS) for managing chronic obstructive pulmonary disease (COPD). Setting Systematic review and network meta-analysis (NMA). Participants 208 randomised clinical trials (RCTs) including 134 692 adults with COPD. Interventions LABA, LAMA and/or ICS, alone or in combination, versus each other or placebo. Primary and secondary outcomes The proportion of patients with moderate-to-severe exacerbations. The number of patients experiencing mortality, pneumonia, serious arrhythmia and cardiovascular-related mortality (CVM) were secondary outcomes. Results NMA was conducted including 20 RCTs for moderate-to-severe exacerbations for 26 141 patients with an exacerbation in the past year. 32 treatments were effective versus placebo including: tiotropium, budesonide/formoterol, salmeterol, indacaterol, fluticasone/salmeterol, indacaterol/glycopyrronium, tiotropium/fluticasone/salmeterol and tiotropium/budesonide/formoterol. Tiotropium/budesonide/formoterol was most effective (99.2% probability of being the most effective according to the Surface Under the Cumulative RAnking (SUCRA) curve). NMA was conducted on mortality (88 RCTs, 97 526 patients); fluticasone/salmeterol was more effective in reducing mortality than placebo, formoterol and fluticasone alone, and was the most effective (SUCRA=71%). NMA was conducted on CVM (37 RCTs, 55 156 patients) and the following were safest: salmeterol versus each OF placebo, tiotropium and tiotropium (Soft Mist Inhaler (SMR)); fluticasone versus tiotropium (SMR); and salmeterol/fluticasone versus tiotropium and tiotropium (SMR). Triamcinolone acetonide was the most harmful (SUCRA=81%). NMA was conducted on pneumonia occurrence (54 RCTs, 61 551 patients). 24 treatments were more harmful, including 2 that increased risk of pneumonia versus placebo; fluticasone and fluticasone/salmeterol. The most harmful agent was fluticasone/salmeterol (SUCRA=89%). NMA was conducted for arrhythmia; no statistically significant differences between agents were identified. Conclusions Many inhaled agents are available for COPD, some are safer and more effective than others. Our results can be used by patients and physicians to tailor administration of these agents. Protocol registration number PROSPERO # CRD42013006725.

Objectives Patient engagement (PE) improves patient, organisation and health system outcomes, but most research is based on primary care. The primary purpose of this study was to describe the characteristics of published empirical research that evaluated PE in hospital health service improvement. Design Scoping review. Methods Five databases were searched from 2006 to September 2016. English language studies that evaluated patient or provider beliefs, participation in PE, influencing factors or impact were eligible. Screening and data extraction were done in triplicate. PE characteristics, influencing factors and impact were extracted and summarised. Results From a total of 3939 search results, 227 studies emerged as potentially relevant; of these, 217 were not eligible, and 10 studies were included in the review. None evaluated behavioural interventions to promote or support PE. While most studies examined involvement in standing committees or projects, patient input and influence on decisions were minimal. Lack of skill and negative beliefs among providers were PE barriers. PE facilitators included careful selection and joint training of patients and providers, formalising patient roles, informal interaction to build trust, involving patients early in projects, small team size, frequent meetings, active solicitation of patient input in meetings and debriefing after meetings. Asking patients to provide insight into problems rather than solutions and deploying provider champions may enhance patient influence on hospital services. Conclusions Given the important role of PE in improving hospital services and the paucity of research on this topic, future research should develop and evaluate behavioural interventions for PE directed at patients and providers informed by the PE barriers and facilitators identified here. Future studies should also assess the impact on various individual and organisational outcomes.

Objectives Interrupted time series (ITS) design involves collecting data across multiple time points before and after the implementation of an intervention to assess the effect of the intervention on an outcome. ITS designs have become increasingly common in recent times with frequent use in assessing impact of evidence implementation interventions. Several statistical methods are currently available for analysing data from ITS designs; however, there is a lack of guidance on which methods are optimal for different data types and on their implications in interpreting results. Our objective is to conduct a scoping review of existing methods for analysing ITS data, to summarise their characteristics and properties, as well as to examine how the results are reported. We also aim to identify gaps and methodological deficiencies. Methods and analysis We will search electronic databases from inception until August 2016 (eg, MEDLINE and JSTOR). Two reviewers will independently screen titles, abstracts and full-text articles and complete the data abstraction. The anticipated outcome will be a summarised description of all the methods that have been used in analysing ITS data in health research, how those methods were applied, their strengths and limitations and the transparency of interpretation/reporting of the results. We will provide summary tables of the characteristics of the included studies. We will also describe the similarities and differences of the various methods. Ethics and dissemination Ethical approval is not required for this study since we are just considering the methods used in the analysis and there will not be identifiable patient data. Results will be disseminated through open access peer-reviewed publications.

Introduction Multimorbidity becomes increasingly prevalent with ageing. Polypharmacy is often associated with multimorbidity because patients accrue medications to treat each individual disease; however, there is uncertainty around the generalisability of disease-specific guidelines. Namely, the extrapolation of results from studies conducted in younger patients to older adults with multimorbidity. The main objective of this scoping review is to explore our current knowledge of the outcomes that older adults with multimorbidity experience from taking prescribed medications. Methods and analysis A scoping review will be conducted to explore what is known about the outcomes experienced by older adults with multimorbidity who are taking guideline-recommended medications and to identify areas for future research. In addition to searching the grey literature, the following databases will be searched from 1990 onward: MEDLINE, EMBASE, PsycINFO and the Cochrane Library. Experimental, quasi-experimental and non-experimental studies consisting of patients ≥65 years old who have two or more comorbid conditions (explicitly grouped together for the purpose of analysis) and who are being prescribed a guideline-recommended prescription medication for a chronic condition will be considered for inclusion in our scoping review. We will describe patient (eg, mortality, morbidity, quality of life) and health system (eg, number of emergency department visits or hospitalisations, cost to third-party payer) outcomes associated with the prescription of medications for older adults who have two or more chronic comorbid conditions. Two reviewers will complete all screening and data abstraction independently. Data will be synthesised with descriptive statistics. Ethics and dissemination Ethics approval is not required because this is a scoping review of published literature. Results will be disseminated through conference presentations and publication in a peer-reviewed journal.

Introduction Colorectal cancer (CRC) poses a serious health problem worldwide. While screening is effective in reducing CRC mortality, participation in screening tests is generally suboptimal and social inequities in participation are frequently reported. The goal of this review is to synthesise factors that influence an individual’s decision to participate in CRC screening, and to explore how those factors vary by sex, ethnicity and socioeconomic status. Data sources A primary search of Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, EMBASE, PsycINFO, and a secondary search of grey literature and articles taken from references of included articles (from inception to July 2013). Design A systematic review and Meta-study synthesis of qualitative studies that address perceived benefits and barriers to participation in CRC screening tests among adults 50 years of age or older. Review methods The two-staged Meta-study methodology by Paterson will be used to conduct this review. In stage 1, similarities/differences, patterns and themes will be identified across three levels of analysis while preserving the context of original studies. In stage 2, synthesis will extend beyond the analysis to generate new theory of the phenomenon through a process called Meta-synthesis. Discussion This review offers to generate a framework to better understand benefits and barriers that affect decision-making to participate in CRC screening among different sectors of the population. This framework will be a relevant tool for policy makers in framing educational materials, for patient-centered communication, and for researchers interested in the science of equity. This review is registered in PROSPERO (registration number: CRD42013005025).

Introduction Knowledge translation (KT also known as research utilisation, translational medicine and implementation science) is a dynamic and iterative process that includes the synthesis, dissemination, exchange and ethically sound application of knowledge to improve health. After the implementation of KT interventions, their impact on relevant outcomes should be monitored. The objectives of this scoping review are to: (1) conduct a systematic search of the literature to identify the impact on healthcare outcomes beyond 1 year, or beyond the termination of funding of the initiative of KT interventions targeting chronic disease management for end-users including patients, clinicians, public health officials, health services managers and policy-makers; (2) identify factors that influence sustainability of effective KT interventions; (3) identify how sustained change from KT interventions should be measured; and (4) develop a framework for assessing sustainability of KT interventions. Methods and analysis Comprehensive searches of relevant electronic databases (eg, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), websites of funding agencies and websites of healthcare provider organisations will be conducted to identify relevant material. We will include experimental, quasi-experimental and observational studies providing information on the sustainability of KT interventions targeting chronic disease management in adults and focusing on end-users including patients, clinicians, public health officials, health services managers and policy-makers. Two reviewers will pilot-test the screening criteria and data abstraction form. They will then screen all citations, full articles and abstract data in duplicate independently. The results of the scoping review will be synthesised descriptively and used to develop a framework to assess the sustainability of KT interventions. Discussion and dissemination Our results will help inform end-users (ie, patients, clinicians, public health officials, health services managers and policy-makers) regarding the sustainability of KT interventions. Our dissemination plan includes publications, presentations, website posting and a stakeholder meeting.

Introduction Alzheimer9s dementia (AD) is the most common cause of dementia, and several organisations, such as the National Institute for Health and Care Excellence, suggest that management of patients with AD should be tailored to their needs. To date, little research has been conducted on the treatment effect in different subgroups of patients with AD. The aim of this study is to examine the comparative effectiveness and safety of cognitive enhancers for different patient characteristics. Methods and analysis We will update our previous literature search from January 2015 forward, using the same terms and electronic databases (eg, MEDLINE) from our previous review. We will additionally search grey literature and scan the reference lists of the included studies. Randomised clinical trials of any duration conducted at any time comparing cognitive enhancers alone or in any combination against other cognitive enhancers, or placebo in adults with AD will be eligible. The outcomes of interest are cognition according to the Mini-Mental State Examination, and overall serious adverse events. For each outcome and treatment comparison, we will perform a Bayesian hierarchical random-effects meta-analysis combining the individual patient data (IPD) from each eligible study. If the identified treatment comparisons form a connected network diagram, we will perform an IPD network meta-analysis (NMA) to estimate subgroup effects for patients with different characteristics, such as AD severity and sex. We will combine aggregated data from studies that we will not be able to obtain IPD, with the IPD provided by the original authors, in a single model. We will use the PRISMA-IPD and PRISMA-NMA statements to report our findings. Ethics and dissemination The findings of this study will be of interest to stakeholders, including decision makers, guideline developers, clinicians, methodologists and patients, and they will help to improve guidelines for the management of patients with AD. Trial registration number CRD42015023507.

Introduction Reducing unnecessary, low-value clinical practice (ie, de-adoption) is key to improving value for money in healthcare, especially among patients admitted to intensive care units (ICUs) where resource consumption exceeds other medical and surgical populations. Research suggests that low-value clinical practices are common in medicine, however systematically and objectively identifying them is a widely cited barrier to de-adoption. We will conduct a scoping review to identify low-value clinical practices in adult critical care medicine that are candidates for de-adoption. Methods and analysis We will systematically search the literature to identify all randomised controlled trials or systematic reviews that focus on diagnostic or therapeutic interventions in adult patients admitted to medical, surgical or specialty ICUs, and are published in 3 general medical journals with the highest impact factor ( New England Journal of Medicine , The Lancet , Journal of the American Medical Association ). 2 investigators will independently screen abstracts and full-text articles against inclusion criteria, and extract data from included citations. Included citations will be classified according to whether or not they represent a repeat examination of the given research question (ie, replication research), and whether the results are similar or contradictory to the original study. Studies with contradictory results will determine clinical practices that are candidates for de-adoption. Ethics and dissemination Our scoping review will use robust methodology to systematically identify a list of clinical practices in adult critical care medicine with evidence supporting their de-adoption. In addition to adding to advancing the study of de-adoption, this review may also serve as the launching point for clinicians and researchers in critical care to begin reducing the number of low-value clinical practices. Dissemination of these results to relevant stakeholders will include tailored presentations at local, national and international meetings, and publication of a manuscript. Ethical approval is not required for this study.

Introduction Individual patient data (IPD) meta-analysis (MA) offers advantages over aggregate MA of using standardised criteria for patient characteristics across trials, and allowing reliable investigation of subgroup effects of interventions. Network meta-analysis (NMA) allows for the comparison of multiple treatments in a comprehensive analysis and the determination of the best treatment among several competing treatments, including those that have never been compared in a head-to-head study. Including IPD in NMA may enable the prevention of misleading inferences due to several biases, such as aggregation bias. Application of IPD-NMA methods in healthcare have begun to appear in medical journals. Our objective is to conduct a scoping review of existing IPD-NMA methods, and summarise their properties. We also aim to describe the characteristics of empirical IPD-NMAs, and examine how their results are reported. Methods and analysis We will search relevant electronic databases from inception until October 2014 (eg, MEDLINE), grey literature, and Google. The scoping review will consider published and unpublished papers that report completion of an IPD-NMA, describe a method, or report the methodological quality of IPD-NMA. We will include IPD-NMA of any quantitative study (eg, experimental, quasiexperimental, observational studies). Two reviewers will independently screen titles, abstracts and full-text articles, and will complete data abstraction. The anticipated outcome will be a collection of all the IPD-NMAs completed to date, and a description of their methods and reporting of results. We will create summary tables providing the characteristics of the included studies, and the various methods. Quantitative data (eg, number of patients) will be summarised by medians and IQRs, and categorical data (eg, type of effect size) by frequencies and percentages. Ethics and dissemination Ethical approval is not required as our study will not include confidential participant data and interventions. We will disseminate our results through an open access, peer-reviewed publication.

Introduction The burden of chronic disease is a global phenomenon, particularly among people aged 65 years and older. More than half of older adults have more than one chronic disease and their care is not optimal. Chronic disease management (CDM) tools have the potential to meet this challenge but they are primarily focused on a single disease, which fails to address the growing number of seniors with multiple chronic conditions. Methods and analysis We will conduct a systematic review alongside a realist review to identify effective CDM tools that integrate one or more high-burden chronic diseases affecting older adults and to better understand for whom, under what circumstances, how and why they produce their outcomes. We will search MEDLINE, EMBASE, CINAHL, AgeLine and the Cochrane Library for experimental, quasi-experimental, observational and qualitative studies in any language investigating CDM tools that facilitate optimal disease management in one or more high-burden chronic diseases affecting adults aged ≥65 years. Study selection will involve calibration of reviewers to ensure reliability of screening and duplicate assessment of articles. Data abstraction and risk of bias assessment will also be performed independently. Analysis will include descriptive summaries of study and appraisal characteristics, effectiveness of each CDM tool (meta-analysis if appropriate); and a realist programme theory will be developed and refined to explain the outcome patterns within the included studies. Ethics and dissemination Ethics approval is not required for this study. We anticipate that our findings, pertaining to gaps in care across high-burden chronic diseases affecting seniors and highlighting specific areas that may require more research, will be of interest to a wide range of knowledge users and stakeholders. We will publish and present our findings widely, and also plan more active dissemination strategies such as workshops with our key stakeholders. Trial registration number Our protocol is registered with PROSPERO (registration number CRD42014014489).

Objective The aim of this study was to evaluate the usability of two formats of a shortened systematic review for clinicians. Materials and methods Usability of the prototypes was assessed using three cycles of iterative testing. 10 participants were asked to complete tasks of locating information or items within two prototypes and ‘think aloud’ while being audio taped. Interviews were also audio recorded and participants completed a systematic usability scale. Results Revisions were made between each iteration in order to address issues identified by participants. Finding information relating to the number of studies in the meta-analysis, and locating the number of studies in the entire systematic review were revealed as areas needing attention during the usability evaluation. Conclusions Iterative testing combined with a multifaceted approach to usability testing offered essential insight into aspects of the prototypes that required modifications. Alterations were made in order to create finalised versions of the two shortened systematic review formats.

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.

Introduction Heart failure (HF) is a leading reason for hospitalisation and readmissions to hospital, particularly among individuals older than 65 years of age. The prognosis of patients with HF is grim, with high rates of mortality risk and hospital readmissions. The transition period early after hospital discharge represents a window of opportunity to positively influence patient outcomes using quality improvement (QI) strategies. However, little is known about which QI interventions exist for early events of HF after discharge, so the main objective of our study is to conduct a scoping review of the literature to determine which QI strategies are effective for reducing hospital readmissions and mortality for patients with HF who transition from the hospital back into independent living. We will also investigate which elements contribute to effective QI strategies. Methods and analysis We will search the literature in MEDLINE, EMBASE, CINAHL and the Cochrane library for randomised controlled trials and systematic reviews evaluating QI interventions aimed at improving outcomes for patients with HF transitioning from the hospital back into the community. Two reviewers will independently apply our eligibility criteria at level 1 (abstract/title) and level 2 (full-text) screening; disagreements will be resolved through consensus. We will extract data in duplicate on study characteristics, population, setting, QI intervention and outcomes. We will synthesise results descriptively and explore QI elements to determine which aspect contributes to its impact. We will also consider synthesis of our data according to several conceptual frameworks such as Wagner9s Chronic Care Model. Discussion and dissemination The findings of this scoping review will be used to determine which elements should comprise a QI intervention aimed at facilitating the transition of newly admitted patients with HF back into the community. We will disseminate our findings through publications, presentations as well as through a stakeholder meeting to generate key messages most relevant to each.

Background Transitions of care between providers are vulnerable periods in healthcare delivery that expose patients to preventable errors and adverse events. Patient discharge from the intensive care unit (ICU) to a medical or surgical hospital ward is one of the most challenging and high risk transitions of care. Approximately 1 in 12 patients discharged will be readmitted to ICU or die before leaving the hospital. Many more patients are exposed to unnecessary healthcare, adverse events and/or are disappointed with the quality of their care. Our objective is to conduct a scoping review by systematically searching the literature to identify ICU discharge planning tools and their supporting evidence-base including barriers and facilitators to their use. Methods and analysis Systematic searching of the published health literature will be conducted to identify the existing ICU discharge planning tools and supporting evidence. Literature (research and non-research) reporting on the tools used to facilitate decision making and/or communication at ICU discharge with patients of any age will be included. Outcomes will include adverse events and provider and patient/family-reported outcomes. Two investigators will independently review the abstracts (screen 1) to identify those meeting the inclusion criteria and then independently assess the full text articles (screen 2) to determine if they meet the inclusion criteria. Data collection will include information on citations and identified tools. A quality assessment will be performed on original research studies. A descriptive summary will be developed for each tool. Ethics and dissemination Our scoping review will synthesise the literature for ICU discharge planning tools and identify the opportunities for knowledge to action and gaps in evidence where primary evidence is necessary. This will serve as the foundational element in a multistep research programme to standardise and improve the quality of care provided to patients during ICU discharge. Ethics approval is not required for this study.