A scoping review shows that no single existing risk of bias assessment tool considers all sources of bias for cross-sectional studies.

OBJECTIVES: Different tools to assess the potential risk of bias (RoB) for cross-sectional studies have been developed, but it is unclear whether all pertinent bias concepts are addressed. We aimed to identify RoB concepts applicable to cross-sectional research validity and to explore coverage for each in existing appraisal tools. STUDY DESIGN AND SETTING: This scoping review followed the Joanna Briggs Institute methodology. We included records of any study design describing or reporting methods, concepts or tools used to consider RoB in health research reported to be descriptive/prevalence survey or analytic/association (cross-sectional) study designs. Synthesis included quantitative and qualitative analysis. RESULTS: Of the 4556 records screened, 90 were selected for inclusion; 67 (74%) described the development of, or validation process for, appraisal tools, 15 (17%) described methodological content or theory relevant to RoB for cross-sectional studies and 8 (9%) records of methodological systematic reviews. Review of methodological reports identified important RoB concepts for both descriptive/prevalence and analytic/association studies. Tools identified (n = 64 unique tools) were either intended to appraise quality or assess RoB in multiple study designs including cross-sectional studies (n = 21; 33%) or cross-sectional designs alone (n = 43; 67%). Several existing tools were modified (n = 17; 27%) for application to cross-sectional studies. The RoB items most frequently addressed in the RoB tools were validity and reliability of the exposure (53%) or outcome (65%) measurement and representativeness of the study population (59%). Most tools did not consider nonresponse or missingness appropriately or at all. CONCLUSION: Assessing cross-sectional studies involve unique RoB considerations. We identified RoB tools designed for broad applicability across various study designs as well as those specifically tailored for cross-sectional studies. However, none of the identified tools comprehensively address all potential biases pertinent to cross-sectional studies. Our findings indicate a need for continued improvement of RoB tools and suggest that the development of context-specific or more precise tools for this study design may be necessary.

Cost-effectiveness of population screening for aortic stenosis.

BACKGROUND AND AIMS: Aortic stenosis (AS) is a progressive disease predominantly affecting elderly patients that carries significant morbidity and mortality without aortic valve replacement, the only proven treatment. Our objective was to determine the cost-effectiveness of AS screening using transthoracic echocardiography (TTE) in a geriatric population from the perspective of the publicly funded healthcare system in Canada. METHODS: Markov models estimating the cost-effectiveness ratio (ICER) for AS screening with a one-time TTE were developed. The model included diagnosed and undiagnosed AS health states, hospitalizations, TAVR and post-TAVR health states. Primary analysis included screening at 70 and 80 years of age with intervention at symptom onset, with scenario analysis included for early intervention at the time of severe asymptomatic AS diagnosis. Monte Carlo simulation of 5000 replications was completed with a lifetime horizon and 1.5% discount for costs and outcomes. RESULTS: Screening for AS at the age of 70 years was associated with an ICER of $156,722 and screening at 80 years of age was associated with an ICER of $28,005, suggesting that screening at 80 years of age is cost-effective when willingness-to-pay per QALY is $50,000. Scenario analysis with early intervention was not cost-effective with an ICER of $142,157 at 70 years, and $124,651 at 80 years. CONCLUSION: Screening for AS at 80 years of age with a one-time TTE, in a Canadian population, improves quality of life and is cost-effective in a publicly funded healthcare system providing TAVR is reserved for symptomatic patients.

Reporting of equity in observational epidemiology: A methodological review.

Background: Observational studies can inform how we understand and address persisting health inequities through the collection, reporting and analysis of health equity factors. However, the extent to which the analysis and reporting of equity-relevant aspects in observational research are generally unknown. Thus, we aimed to systematically evaluate how equity-relevant observational studies reported equity considerations in the study design and analyses. Methods: We searched MEDLINE for health equity-relevant observational studies from January 2020 to March 2022, resulting in 16 828 articles. We randomly selected 320 studies, ensuring a balance in focus on populations experiencing inequities, country income settings, and coronavirus disease 2019 (COVID-19) topic. We extracted information on study design and analysis methods. Results: The bulk of the studies were conducted in North America (n = 95, 30%), followed by Europe and Central Asia (n = 55, 17%). Half of the studies (n = 171, 53%) addressed general health and well-being, while 49 (15%) focused on mental health conditions. Two-thirds of the studies (n = 220, 69%) were cross-sectional. Eight (3%) engaged with populations experiencing inequities, while 22 (29%) adapted recruitment methods to reach these populations. Further, 67 studies (21%) examined interaction effects primarily related to race or ethnicity (48%). Two-thirds of the studies (72%) adjusted for characteristics associated with inequities, and 18 studies (6%) used flow diagrams to depict how populations experiencing inequities progressed throughout the studies. Conclusions: Despite over 80% of the equity-focused observational studies providing a rationale for a focus on health equity, reporting of study design features relevant to health equity ranged from 0-95%, with over half of the items reported by less than one-quarter of studies. This methodological study is a baseline assessment to inform the development of an equity-focussed reporting guideline for observational studies as an extension of the well-known Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guideline.

Cardiac PET Myocardial Blood Flow Quantification Assessment of Early Cardiac Allograft Vasculopathy.

BACKGROUND: Positron emission tomography (PET) has demonstrated utility for diagnostic and prognostic assessment of cardiac allograft vasculopathy (CAV) but has not been evaluated in the first year after transplant. OBJECTIVES: The authors sought to evaluate CAV at 1 year by PET myocardial blood flow (MBF) quantification. METHODS: Adults at 2 institutions enrolled between January 2018 and March 2021 underwent prospective 3-month (baseline) and 12-month (follow-up) post-transplant PET, endomyocardial biopsy, and intravascular ultrasound examination. Epicardial CAV was assessed by intravascular ultrasound percent intimal volume (PIV) and microvascular CAV by endomyocardial biopsy. RESULTS: A total of 136 PET studies from 74 patients were analyzed. At 12 months, median PIV increased 5.6% (95% CI: 3.6%-7.1%) with no change in microvascular CAV incidence (baseline: 31% vs follow-up: 38%; P = 0.406) and persistent microvascular disease in 13% of patients. Median capillary density increased 30 capillaries/mm2 (95% CI: -6 to 79 capillaries/mm2). PET myocardial flow reserve (2.5 ± 0.7 vs 2.9 ± 0.8; P = 0.001) and stress MBF (2.7 ± 0.6 vs 2.9 ± 0.6; P = 0.008) increased, and coronary vascular resistance (CVR) (49 ± 13 vs 47 ± 11; P = 0.214) was unchanged. At 12 months, PET and PIV had modest correlation (stress MBF: r = -0.35; CVR: r = 0.33), with lower stress MBF and higher CVR across increasing PIV tertiles (all P < 0.05). Receiver-operating characteristic curves for CAV defined by upper-tertile PIV showed areas under the curve of 0.74 for stress MBF and 0.73 for CVR. CONCLUSIONS: The 1-year post-transplant PET MBF is associated with epicardial CAV, supporting potential use for early noninvasive CAV assessment. (Early Post Transplant Cardiac Allograft Vasculopahty [ECAV]; NCT03217786).

Cost-Effectiveness of Colchicine for Recurrent Cardiovascular Events.

Background: Colchicine is an anti-inflammatory therapy with a low associated cost that has been shown in 2 large studies to reduce cardiovascular (CV) events, but its use is associated with side effects. The main objective for this analysis is to determine whether colchicine therapy is cost-effective for the prevention of recurrent CV events in patients who have suffered a myocardial infarction (MI). Methods: A decision model was developed to estimate the healthcare costs in Canadian dollars and the clinical outcomes among patients who have suffered an MI and are treated with colchicine. Probabilistic Markov modelling was used in combination with Monte Carlo simulation to derive expected lifetime costs and quality-adjusted life-years, which permitted the calculation of incremental cost-effectiveness ratios. Models were derived for both short-term (20 months) and long-term (lifelong) colchicine use in this population. Results: Long-term colchicine use was dominant over standard of care, with lower average lifetime costs per patient (CAD$91,552.80 vs $97,085.84) and a higher average number of quality-adjusted life-years per patient (19.92 vs 19.80). Short-term colchicine use also dominated over standard of care. Results were consistent over a range of scenario analyses. Conclusions: Based on 2 large randomized controlled trials, treatment of patients post-MI with colchicine appears cost-effective, compared to the standard of care at the current price. Based on these studies and currently accepted willingness-to-pay thresholds in Canada, healthcare payers could consider funding long-term colchicine therapy for CV secondary prevention while we await results from ongoing trials.

Contexte: La colchicine est un traitement anti-inflammatoire peu coûteux qui, selon deux grandes études, réduit le taux d'événements cardiovasculaires (CV), mais son utilisation est également associée à des effets secondaires. L'objectif principal de cette analyse était de déterminer si le traitement par la colchicine présente un rapport coût-efficacité intéressant en prévention des événements CV récurrents chez les patients ayant subi un infarctus du myocarde (IM). Méthodologie: Un modèle décisionnel a été mis au point pour estimer les coûts des soins de santé en dollars canadiens et les issues cli-niques chez les patients qui ont subi un IM et qui sont traités par la colchicine. Un modèle probabiliste de Markov a été utilisé en association avec une simulation de Monte-Carlo pour obtenir le coût attendu pendant la vie et le nombre d'années de vie ajustées en fonction de la qualité, données qui ont permis de calculer les rapports coût-efficacité différentiels. Les modèles ont été adaptés pour l'utilisation de la colchicine à court terme (20 mois) et à long terme (à vie) dans la même population. Résultats: L'utilisation de colchicine à long terme donnait de meilleurs résultats que le traitement de référence, avec un coût moyen à vie par patient plus faible (91 552,80 $ CA c. 97 085,84 $ CA) et un plus grand nombre moyen d'années de vie ajustées selon la qualité (19,92 c. 19,80). L'utilisation à court terme de la colchicine donnait aussi de meilleurs résultats que le traitement de référence. Ces résultats ont été observés pour un éventail de scénarios analysés. Conclusions: Selon deux grands essais randomisés contrôlés, le traitement par la colchicine des patients ayant subi un IM semble avoir un meilleur rapport coût-efficacité que le traitement de référence en fonction des coûts actuels. Selon ces études et les seuils de propension à payer actuellement acceptés au Canada, les payeurs pourraient envisager de financer le traitement à long terme par la colchicine en prévention d'événements CV secondaires, jusqu'à l'obtention des résultats des essais en cours.

Prioritising Cochrane reviews to be updated with health equity focus.

BACKGROUND: The prioritisation of updating published systematic reviews of interventions is vital to prevent research waste and ensure relevance to stakeholders. The consideration of health equity in reviews is also important to ensure interventions will not exacerbate the existing inequities of the disadvantaged if universally implemented. This study aimed to pilot a priority setting exercise based on systematic reviews of interventions published in the Cochrane Library, to identify and prioritise reviews to be updated with a focus on health equity. METHODS: We conducted a priority setting exercise with a group of 13 international stakeholders. We identified Cochrane reviews of interventions that showed a reduction in mortality, had at least one Summary of Findings table and that focused on one of 42 conditions with a high global burden of disease from the 2019 WHO Global Burden of Disease report. This included 21 conditions used as indicators of success of the United Nations Universal Health Coverage in attaining the Sustainable Development Goals. Stakeholders prioritised reviews that were relevant to disadvantaged populations, or to characteristics of potential disadvantage within the general population. RESULTS: After searching for Cochrane reviews of interventions within 42 conditions, we identified 359 reviews that assessed mortality and included at least one Summary of Findings table. These pertained to 29 of the 42 conditions; 13 priority conditions had no reviews with the outcome mortality. Reducing the list to only reviews showing a clinically important reduction in mortality left 33 reviews. Stakeholders ranked these reviews in order of priority to be updated with a focus on health equity. CONCLUSIONS: This project developed and implemented a methodology to set priorities for updating systematic reviews spanning multiple health topics with a health equity focus. It prioritised reviews that reduce overall mortality, are relevant to disadvantaged populations, and focus on conditions with a high global burden of disease. This approach to the prioritisation of systematic reviews of interventions that reduce mortality provides a template that can be extended to reducing morbidity, and the combination of mortality and morbidity as represented in Disability-Adjusted Life Years and Quality-Adjusted Life Years.

Combining Aortic Size With Arterial Hemodynamics Enhances Assessment of Future Thoracic Aortic Aneurysm Expansion.

BACKGROUND: Thoracic aortic aneurysm (TAA) is a deadly disease whose current method for risk stratification (aneurysm size) is imperfect. We sought to evaluate whether combining aortic size with hemodynamic measures that reflect the aorta's function was superior to aortic size alone in the assessment of TAA expansion. METHODS: One hundred thirty-seven nonoperated participants with TAA were followed prospectively. Aortic stiffness and pulsatile hemodynamics were noninvasively assessed at baseline with a combination of arterial tonometry with echocardiography using validated methodology. Aneurysm growth was calculated from standard imaging modalities. Multivariable linear regression models adjusted for potential confounders evaluated the association of aneurysm size and arterial hemodynamics, alone and in combination, with TAA growth. RESULTS: Sixty-nine percent of participants were male. Mean ± SD age, baseline aneurysm size, follow-up, and aneurysm expansion were, respectively, 62.2 ± 11.4 years, 45.9 ± 4.0 mm, 4.5 ± 1.9 years, and 0.41 ± 0.46 mm/year. In the linear regression models, the standardised ß (ß∗) for the association of aneurysm size with aneurysm expansion was 0.178 (P = 0.044). This was improved by combining aortic size with most measures of aortic function, with ß∗ ranging from 0.192 (for aneurysm size combined with central diastolic blood pressure) to 0.484 (for aneurysm size combined with carotid-femoral pulse-wave velocity) (P ≤ 0.05 for each). CONCLUSIONS: Combining aneurysm size with measures of arterial function improves assessment of aneurysm growth over TAA size alone, which is the standard for clinical decisions in TAA. Thus, combining aneurysm size with measures of aortic function provides a clinical advantage in the assessment of TAA disease activity.

Assessment of the quality and content of clinical practice guidelines (CPGs) for vitamin D and for immigrants using the AGREE-II instrument: a protocol for systematic review.

INTRODUCTION: Worldwide, more immigrants experience vitamin D (vitD) deficiency than non-immigrants, which is attributed to ethnic variations, place or region of birth, skin pigmentation, clothing style, and resettlement-related changes in diet, physical activity, and sun exposure. Current recommendations in clinical practice guidelines (CPGs) concerning vitD are inadequate to address vitD deficiency among immigrants. CPGs may also lack guidance for physicians on vitD supplementation for immigrants. Moreover, there are concerns about the overall quality of these CPGs. OBJECTIVES: This systematic review will collate and critically appraise CPGs relevant to immigrants' health and vitD. Moreover, we will evaluate whether the CPGs of vitD including recommendations for immigrants and clarify whether the CPGs of immigrants include recommendations on vitD. METHODS: A systematic search of Ovid MEDLINE® ALL, EMBASE, and Turning Research Into Practice (TRIP) electronic databases, guideline repositories, and gray literature will be conducted to identify relevant CPGs. Two reviewers will independently evaluate the methodological quality of the retrieved guidelines using the Appraisal of Guidelines, Research, and Evaluation-II (AGREE-II) instrument. CPGs scoring ≥60% in at least four domains, including "rigor of development," will be considered high quality. CONCLUSION: Evaluating the quality and content of relevant CPGs may support researchers in developing national and global guidelines for immigrants. Furthermore, it may support vitD testing, nutritional counseling, and supplementation for vulnerable immigrant sub-populations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021240562.

Cost-Effectiveness of Canakinumab From a Canadian Perspective for Recurrent Cardiovascular Events.

Background: Cardiovascular (CV) disease is a condition with high levels of morbidity and mortality. Canakinumab is a novel monoclonal antibody therapy that has been shown to reduce CV events but is associated with side effects and high cost. The main objective for this analysis is to determine whether canakinumab use is cost-effective for the prevention of recurrent CV events. Methods: A decision model was developed to estimate the direct costs and outcomes among patients who have suffered a myocardial infarction and are treated with canakinumab. A lifetime study horizon was used to analyze the base-case costs and utilities from the perspective of the Canadian publicly funded healthcare system. Markov modeling was used in combination with Monte Carlo simulation to derive expected values for costs and quality-adjusted life years (QALYs), permitting the calculation of incremental cost-effectiveness ratios. Results: Canakinumab was associated with higher average lifetime costs per patient ($457,982 vs $82,565) and higher average QALYs per patient (14.90 vs 14.20), compared with standard of care. Thus, the incremental cost per QALY gained for canakinumab treatment vs standard-of-care therapy was $535,365. The probability that canakinumab treatment is cost-effective was 0%. Results were consistent over a range of scenario analyses. Conclusions: Treatment of patients post-myocardial infarction with canakinumab is not cost-effective, compared with standard-of-care therapy at the current price. Based on currently accepted willingness-to-pay thresholds in Canada, a reduction in price of 91% is required to yield a cost per patient that would be considered appropriate.

Introduction: La maladie cardiovasculaire (CV) est une affection à forts taux de morbidité et de mortalité. Le canakinumab est un nouveau traitement par anticorps monoclonaux qui s'est avéré diminuer les événements CV, mais qui est associé à des effets secondaires et des coûts élevés. Le principal objectif de la présente analyse est de déterminer si l'utilisation du canakinumab est rentable dans la prévention des événements CV récidivants. Méthodes: Nous avons élaboré un modèle de prise de décision pour estimer les coûts directs et les résultats chez les patients qui ont souffert d'un infarctus du myocarde et qui sont traités par canakinumab. Nous avons utilisé un horizon d'étude sur la vie entière pour l'analyse coût-utilité de référence selon la perspective du système de soins de santé du Canada financé par l'État. La modélisation de Markov qui a été utilisée en combinaison avec la simulation Monte Carlo pour obtenir les valeurs attendues des coûts et des années de vie ajustées en fonction de la qualité (AVAQ) a permis le calcul des ratios coûts-efficacité différentiels. Résultats: Le canakinumab a été associé à des coûts moyens sur la vie entière plus élevés par patient (457 982 $ vs 82 565 $) et une AVAQ moyenne plus élevée par patient (14,90 vs 14,20) que le traitement selon la norme de soins. Par conséquent, le coût différentiel par AVAQ obtenu avec le traitement par canakinumab vs le traitement selon la norme de soins était de 535 365 $. La probabilité que le traitement par canakinumab soit rentable était de 0 %. Les résultats étaient cohérents dans un éventail d'analyses de scénarios. Conclusions: Le traitement des patients après un infarctus du myocarde par canakinumab n'est pas rentable comparativement au traitement selon la norme de soins au prix actuel. Selon les seuils de propension à payer actuellement acceptés au Canada, une réduction du prix de 91 % est requise pour obtenir un coût par patient qui serait considéré comme approprié.

How effects on health equity are assessed in systematic reviews of interventions.

BACKGROUND: Enhancing health equity is endorsed in the Sustainable Development Goals. The failure of systematic reviews to consider potential differences in effects across equity factors is cited by decision-makers as a limitation to their ability to inform policy and program decisions.  OBJECTIVES: To explore what methods systematic reviewers use to consider health equity in systematic reviews of effectiveness. SEARCH METHODS: We searched the following databases up to 26 February 2021: MEDLINE, PsycINFO, the Cochrane Methodology Register, CINAHL, Education Resources Information Center, Education Abstracts, Criminal Justice Abstracts, Hein Index to Foreign Legal Periodicals, PAIS International, Social Services Abstracts, Sociological Abstracts, Digital Dissertations and the Health Technology Assessment Database. We searched SCOPUS to identify articles that cited any of the included studies on 10 June 10 2021. We contacted authors and searched the reference lists of included studies to identify additional potentially relevant studies. SELECTION CRITERIA: We included empirical studies of cohorts of systematic reviews that assessed methods for measuring effects on health inequalities. We define health inequalities as unfair and avoidable differences across socially stratifying factors that limit opportunities for health. We operationalised this by assessing studies which evaluated differences in health across any component of the PROGRESS-Plus acronym, which stands for Place of residence, Race/ethnicity/culture/language, Occupation, Gender or sex, Religion, Education, Socioeconomic status, Social capital. "Plus" stands for other factors associated with discrimination, exclusion, marginalisation or vulnerability such as personal characteristics (e.g. age, disability), relationships that limit opportunities for health (e.g. children in a household with parents who smoke) or environmental situations which provide limited control of opportunities for health (e.g. school food environment). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data using a pre-tested form. Risk of bias was appraised for included studies according to the potential for bias in selection and detection of systematic reviews.  MAIN RESULTS: In total, 48,814 studies were identified and the titles and abstracts were screened in duplicate. In this updated review, we identified an additional 124 methodological studies published in the 10 years since the first version of this review, which included 34 studies. Thus, 158 methodological studies met our criteria for inclusion. The methods used by these studies focused on evidence relevant to populations experiencing health inequity (108 out of 158 studies), assess subgroup analysis across PROGRESS-Plus (26 out of 158 studies), assess analysis of a gradient in effect across PROGRESS-Plus (2 out of 158 studies) or use a combination of subgroup analysis and focused approaches (20 out of 158 studies). The most common PROGRESS-Plus factors assessed were age (43 studies), socioeconomic status in 35 studies, low- and middle-income countries in 24 studies, gender or sex in 22 studies, race or ethnicity in 17 studies, and four studies assessed multiple factors across which health inequity may exist. Only 16 studies provided a definition of health inequity. Five methodological approaches to consider health equity in systematic reviews of effectiveness were identified: 1) descriptive assessment of reporting and analysis in systematic reviews (140 of 158 studies used a type of descriptive method); 2) descriptive assessment of reporting and analysis in original trials (50 studies); 3) analytic approaches which assessed differential effects across one or more PROGRESS-Plus factors (16 studies); 4) applicability assessment (25 studies) and 5) stakeholder engagement (28 studies), which is a new finding in this update and examines the appraisal of whether relevant stakeholders with lived experience of health inequity were included in the design of systematic reviews or design and delivery of interventions. Reporting for both approaches (analytic and applicability) lacked transparency and was insufficiently detailed to enable the assessment of credibility. AUTHORS' CONCLUSIONS: There is a need for improvement in conceptual clarity about the definition of health equity, describing sufficient detail about analytic approaches (including subgroup analyses) and transparent reporting of judgments required for applicability assessments in order to consider health equity in systematic reviews of effectiveness.

Sex differences after coronary artery bypass grafting with a second arterial conduit.

OBJECTIVES: Double arterial conduit use during coronary artery bypass grafting is associated with improved clinical outcomes compared with single arterial conduits in the general population. However, the sex-specific outcomes of this strategy remain unknown and are needed to inform sex-specific revascularization guidelines. METHODS: We conducted a population-based, retrospective cohort study of all Ontarians who underwent primary isolated coronary artery bypass grafting with single arterial conduits or double arterial conduits between October 2008 and September 2017. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiac and cerebrovascular events, defined as a composite of myocardial infarction, heart failure hospitalization, repeat revascularization, and stroke. We used inverse probability of treatment weighting to account for group imbalances. RESULTS: A total of 9135 women and 36,748 men underwent coronary artery bypass grafting. At 30 days, there was no between-group difference in mortality or major adverse cardiac and cerebrovascular events in men. However, among women, a double arterial conduit was associated with an increased rate of 30-day death (hazard ratio, 1.48; 95% confidence interval, 1.23-1.79) and major adverse cardiac and cerebrovascular events (hazard ratio, 1.32; 95% confidence interval, 1.14-1.51). The risk of medium-term mortality with double arterial conduits was less in men (hazard ratio, 0.88; 95% confidence interval, 0.84-0.92) and women (hazard ratio, 0.87; 95% confidence interval, 0.81-0.94), as was the medium-term risk of major adverse cardiac and cerebrovascular events (hazard ratio, 0.91; 95% confidence interval, 0.87-0.94) [men]; hazard ratio, 0.91; 95% confidence interval, 0.86-0.97) [women]). The incremental improvement in 9-year survival was 4.0% in women with a double arterial conduit and 0.9% in men. CONCLUSIONS: Double arterial conduit is associated with better medium-term survival and cardiovascular outcomes in both sexes. Double arterial conduits are associated with increased perioperative risk in women, but the medium-term benefit is greater than in men.

Remote Monitoring of Cardiovascular Implantable Electronic Devices in Canada: Survey of Patients and Device Health Care Professionals.

BACKGROUND: Remote monitoring is used to supplement in-clinic follow-up for patients with cardiac implantable electronic devices (CIEDs) every 6-12 months. There is a need to optimize remote management for CIEDs because of the consistent increases in CIED implants over the past decade. The objective of this study was to investigate real and perceived barriers to the use of remote patient management strategies in Canada and to better understand how remote models of care can be optimized. METHODS: We surveyed 512 CIED patients and practitioners in 22 device clinics in Canada. RESULTS: Device clinic surveys highlighted significant variation and inconsistency in follow-up care for in-clinic and remote visits across and within clinics. This survey showed that funding policies and management of additional workflow are barriers to optimal use and uptake. Despite this, device clinics perceive remote follow-up as a valuable resource and an efficient way to manage patient follow-up. Patients were broadly satisfied with their CIED follow-up care but identified barriers related to coordination of care, visit logistics, and information needs. Views varied as a function of clinical or sociodemographic characteristics. Most patients (n = 228; 91%) expressed a desire to receive a phone call from their device clinic after a remote transmission has been received. CONCLUSIONS: Lack of a unified, guideline-supported approach to follow-up after CIED implant, and discrepant funding policies across jurisdictions, are significant barriers to the use of remote patient management strategies in Canada. Efforts to increase or expand use of remote follow-up must recognize these barriers and the needs of specific subgroups of patients.

INTRODUCTION: La télésurveillance sert de complément à la consultation en clinique des patients porteurs d'un dispositif cardiaque électronique implantable (DCEI) tous les 6 à 12 mois. Il est nécessaire d'optimiser la prise en charge à distance des patients porteurs de DCEI en raison de la constante augmentation des implantations de DCEI au cours de la dernière décennie. L'objectif de la présente étude était d'examiner les obstacles réels et perçus à l'utilisation des stratégies de prise en charge à distance des patients du Canada et de mieux comprendre la façon d'optimiser les modèles de soins à distance. MÉTHODES: Nous avons interrogé 512 patients porteurs de DCEI et praticiens de 22 cliniques spécialisées en DCEI du Canada. RÉSULTATS: Les enquêtes des cliniques spécialisées en DCEI ont fait ressortir la variation importante et le manque d'uniformité dans les soins de suivi lors des consultations en clinique et à distance au sein de toutes les cliniques et entre elles. Cette enquête a montré que les politiques de financement et la gestion du flux de travail supplémentaire sont les obstacles qui empêchent l'utilisation optimale et l'adoption. Malgré cela, les cliniques spécialisées en DCEI perçoivent le suivi à distance comme une ressource très utile et un moyen efficace de prendre en charge le suivi du patient. Les patients étaient dans l'ensemble satisfaits de leurs soins de suivi relatifs à leur DCEI, mais relevaient des obstacles liés à la coordination des soins, à la logistique des consultations et à leurs besoins d'information. Les points de vue variaient en fonction des caractéristiques cliniques et sociodémographiques. La plupart des patients (n = 228 ; 91 %) ont fait part de leur souhait de recevoir un appel téléphonique de leur clinique spécialisée en DCEI après la réception de la transmission à distance. CONCLUSIONS: L'absence d'une approche unifiée et fondée sur les lignes directrices qui porte sur le suivi après l'implantation de DCEI, et la divergence des politiques de financement des provinces et territoires sont des obstacles importants à l'utilisation de stratégies de prise en charge à distance des patients au Canada. Les efforts visant à accroître ou à étendre l'utilisation du suivi à distance doivent tenir compte de ces obstacles et des besoins des sous-groupes particuliers de patients.

Remote-only monitoring for patients with cardiac implantable electronic devices: a before-and-after pilot study.

BACKGROUND: Outcomes for patients with cardiac implantable electronic devices are better when follow-up incorporates remote monitoring technology in addition to in-clinic visits. For patients with implantable devices, we sought to determine the feasibility, safety and associated health care utilization of remote-only follow-up, along with its effects on patients' quality of life and costs. METHODS: This multicentre before-and-after pilot study involved patients with new or existing pacemakers or implantable cardioverter defibrillators. The "before" phase of the study spanned the period October 2015 to February 2017; the "after" phase spanned the period October 2016 to February 2018. The exposure was remote-only follow-up in combination with Remote View, a service that facilitates access to device data, allowing device settings to be viewed remotely to facilitate remote programming. Outcomes at 12 months were feasibility (adherence to remote monitoring), safety (rate of adverse events) and health care utilization (remote and in-clinic appointments). We also assessed quality of life, using 3 validated scales, and costs, taking into account both health care system and patient costs. RESULTS: A total of 176 patients were enrolled. Adherence (defined as at least 1 successful remote transmission during follow-up) was 87% over a mean follow-up of 11.7 (standard deviation 2.2) months. There was a reduction in in-clinic visits at specialized sites among patients with both implantable defibrillators (26 v. 5, p < 0.001, n = 48) and pacemakers (42 v. 10, p < 0.001, n = 51). There was no significant change in visits to community sites for patients with defibrillators (13 v. 17, p = 0.3, n = 48). The composite rate of death, stroke, cardiovascular hospitalization and device-related hospitalization was 7% (n = 164). No adverse events were linked to the intervention. There was no change in quality-of-life scales between baseline and 12 months. Health care costs were reduced by 31% for patients with defibrillators and by 44% for those with pacemakers. INTERPRETATION: This pilot study showed the feasibility of remote-only follow-up, with no increase in adverse clinical outcomes and no effect on quality of life, but with reductions in costs and health care utilization. These results support progression to a larger-scale study of whether superior effectiveness and reduced cost can be achieved, with preservation of safety, through use of remote-only follow-up. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT02585817.

GRADE Concept Paper 1: Validating the "F.A.C.E" instrument using stakeholder perceptions of feasibility, acceptability, cost, and equity in guideline implement.

BACKGROUND AND OBJECTIVE: To present a structured approach for assessing stakeholder perceptions and implementing the approach in guideline development. METHODS: This work was carried out by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Equity and Stakeholder Engagement Project Groups through brainstorming and iterative frameworks, stakeholder engagement, pilot testing, refinement of ideas, using input from workshops, and discussions at GRADE Working Group meetings to produce this document, which constitutes a GRADE conceptual article on implementation. RESULTS: We introduce the FACE implementation criteria, feasibility, acceptability, cost, and equity; priority; and "intent to implement" criterion. We outline the implementation importance of networks and approaches to patient and other stakeholder engagement. Implementation is often highly contextual and can benefit from stakeholder engagement and other assessments. Our FACE approach provides stakeholder questions and language to inform guideline implementation and tools. CONCLUSION: The FACE criteria propose a series of knowledge translation questions to guide the assessment of implementation for evidence-based guidelines. It is desirable for guideline developers to use a conceptual approach, such as FACE, to tailor implementation and inform end of guideline dissemination and knowledge translation activities.

Barriers in accessing medical cannabis for children with drug-resistant epilepsy in Canada: A qualitative study.

INTRODUCTION: The use of medical cannabis to treat drug-resistant epilepsy in children is increasing; however, there has been limited study of the experiences of parents with the current system of accessing medical cannabis for their children. METHODS: In this qualitative study, we used a patient-centered access to care framework to explore the barriers faced by parents of children with drug-resistant epilepsy when trying to access medical cannabis in Canada. We conducted semistructured interviews with 19 parents to elicit their experiences with medical cannabis. We analyzed the data according to five dimensions of access, namely approachability, acceptability, availability, affordability, and appropriateness. RESULTS: Parents sought medical cannabis as a treatment because of a perceived unmet need stemming from the failure of antiepileptic drugs to control their children's seizures. Medical cannabis was viewed as an acceptable treatment, especially compared with adding additional antiepileptic drugs. After learning about medical cannabis from the media, friends and family, or other parents, participants sought authorization for medical use. However, most encountered resistance from their child's neurologist to discuss and/or authorize medical cannabis, and many parents experienced difficulty in obtaining authorization from a member of the child's existing care team, leading them to seek authorization from a cannabis clinic. Participants described spending up to $2000 per month on medical cannabis, and most were frustrated that it was not eligible for reimbursement through public or private insurance programs. CONCLUSIONS: Parents pursue medical cannabis as a treatment for their children's drug-resistant epilepsy because of a perceived unmet need. However, parents encounter barriers in accessing medical cannabis in Canada, and strategies are needed to ensure that children using medical cannabis receive proper care from healthcare professionals with training in epilepsy care, antiepileptic drugs, and medical cannabis.

Economic Evaluation of Cannabinoid Oil for Dravet Syndrome: A Cost-Utility Analysis.

INTRODUCTION: Cannabinoid oils are being increasingly used to treat Dravet syndrome, yet the long-term costs and outcomes of this approach are unknown. Thus, we examined the cost effectiveness of cannabinoid oil as an adjunctive treatment (added to clobazam and valproate), compared with adjunctive stiripentol or with clobazam and valproate alone, for the treatment of Dravet syndrome in children. METHODS: We performed a probabilistic cost-utility analysis from the perspective of the Canadian public health care system, comparing cannabinoid oil and stiripentol (both on a background of clobazam and valproate) with clobazam and valproate alone. Costs and quality-adjusted life-years (QALYs) were estimated using a Markov model that followed a cohort of children aged from 5 to 18 years through model states related to seizure frequency. Model inputs were obtained from the literature. The cost effectiveness of adjunctive cannabinoid oil, adjunctive stiripentol, and clobazam/valproate alone was assessed through sequential analysis. The influence of perspective and other assumptions were explored in scenario analyses. All costs are expressed in 2019 Canadian dollars, and costs and QALYs were discounted at a rate of 1.5% per year. RESULTS: The incremental cost per QALY gained with the use of adjunctive cannabinoid oil, from the health care system perspective, was $32,399 compared with clobazam and valproate. Stiripentol was dominated by cannabinoid oil, producing fewer QALYs at higher costs. At a willingness-to-pay threshold of $50,000, cannabinoid oil was the optimal treatment in 76% of replications. From a societal perspective, cannabinoid oil dominated stiripentol and clobazam/valproate. The interpretation of the results was insensitive to model and input assumptions. CONCLUSION: Compared with clobazam/valproate, adjunctive cannabinoid oil may be a cost-effective treatment for Dravet syndrome, if a decision maker is willing to pay at least $32,399 for each QALY gained. The opportunity costs of continuing to fund stiripentol, but not cannabinoid oil, should be considered.

Incorporation of renal function in mortality risk assessment for pulmonary arterial hypertension.

BACKGROUND: Risk assessment is important for prognostication and individualized treatment decisions for patients with pulmonary arterial hypertension (PAH). The purpose was (1) to compare contemporary risk assessment tools and (2) to determine the prognostic significance of risk parameters of kidney function and whether they can further improve risk prediction for patients with PAH. METHODS: We identified a cohort of treatment-naive patients (n = 211) who received an incident diagnosis of PAH at the University of Ottawa Heart Institute. Using demographics, disease characteristics, and hemodynamic data at diagnosis, we categorized patients as low, intermediate, or high risk according to current European guidelines (European Society of Cardiology [ESC]) and registry to evaluate early and long-term pulmonary arterial hypertension disease management (REVEAL) risk scores. The primary end-point was transplant-free survival (TFS). RESULTS: Patients were predominantly women (64.6%) with World Health Organization function Class III symptoms (66.5%). The median TFS was 7.09 years. There was little agreement between ESC- and REVEAL-based risk estimates (weighted kappa = 0.21-0.34). Although both the ESC (log-rank, p = 0.0002) and REVEAL algorithms stratified TFS risk (p < 0.0001), the REVEAL score provided superior discrimination (C-statistic = 0.70 vs 0.59, p = 0.004). Renal function at diagnosis (p < 0.0001) and Δ renal function at 6 months (p < 0.0001) were identified as novel risk parameters and served to reclassify some patients in the intermediate-risk category to a lower or higher risk stratum (p < 0.0001). CONCLUSION: REVEAL-based strategies provide superior TFS risk discrimination to ESC/European Respiratory Society-based approaches. However, the classification of intermediate-risk patients varied significantly across tools. We demonstrate the importance of renal function, which further improved the stratification of risk in patients with PAH, particularly in patients who are considered intermediate risk.

Reporting of health equity considerations in cluster and individually randomized trials.

BACKGROUND: The randomized controlled trial (RCT) is considered the gold standard study design to inform decisions about the effectiveness of interventions. However, a common limitation is inadequate reporting of the applicability of the intervention and trial results for people who are "socially disadvantaged" and this can affect policy-makers' decisions. We previously developed a framework for identifying health-equity-relevant trials, along with a reporting guideline for transparent reporting. In this study, we provide a descriptive assessment of health-equity considerations in 200 randomly sampled equity-relevant trials. METHODS: We developed a search strategy to identify health-equity-relevant trials published between 2013 and 2015. We randomly sorted the 4316 records identified by the search and screened studies until 100 individually randomized (RCTs) and 100 cluster randomized controlled trials (CRTs) were identified. We developed and pilot-tested a data extraction form based on our initial work, to inform the development of our reporting guideline for equity-relevant randomized trials. RESULTS: In total, 39 trials (20%) were conducted in a low- and middle-income country and 157 trials (79%) in a high-income country focused on socially disadvantaged populations (78% CRTs, 79% RCTs). Seventy-four trials (37%) reported a subgroup analysis across a population characteristic associated with disadvantage (25% CRT, 49% RCTs), with 19% of included studies reporting subgroup analyses across sex, 9% across race/ethnicity/culture, and 4% across socioeconomic status. No subgroup analyses were reported for place of residence, occupation, religion, education, or social capital. One hundred and forty-one trials (71%) discussed the applicability of their results to one or more socially disadvantaged populations (68% of CRT, 73% of RCT). DISCUSSION: In this set of trials, selected for their relevance to health equity, data that were disaggregated for socially disadvantaged populations were rarely reported. We found that even when the data are available, opportunities to analyze health-equity considerations are frequently missed. The recently published equity extension of the Consolidated Reporting Standards for Randomized Trials (CONSORT-Equity) may help improve delineation of hypotheses related to socially disadvantaged populations, and transparency and completeness of reporting of health-equity considerations in RCTs. This study can serve as a baseline assessment of the reporting of equity considerations.

Study protocol: Worldwide comparison of vitamin D status of immigrants from different ethnic origins and native-born populations-a systematic review and meta-analysis.

BACKGROUND: A growing body of literature indicates that, worldwide, immigrants experience health deterioration after their arrival into their adopted country, and moreover, they have lower vitamin D compared to the native-born population. We plan to review if the levels of vitamin D are comparable between different ethnic groups in different regions of the world with those of native-born populations and to identify the possible associations between vitamin D deficiency and disease status among immigrants. METHODS/DESIGN: A systematic review and meta-analysis will be conducted following the methods of the Cochrane handbook for systematic reviews. A literature search was performed to identify studies on immigrants and vitamin D. The primary outcome is vitamin D levels, and the secondary outcome is any vitamin D deficiency-related disease. Study design and participant characteristics will be extracted, including ethnicity, country of birth and/or origin, and the host country. Descriptive and meta-analytic summaries of the outcomes will be derived. Distiller-SR and RevMan will be used respectively for data management and meta-analysis. DISCUSSION: This systematic review may partially help clarify vitamin D-related health deterioration in migrants; moreover, to develop a global guideline that specifies sub-populations, in which the evidence and vitamin D-related recommendations might differ from the overall immigrant population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018086729.