Peter Jüni

Aims To conduct a meta‐analysis of randomized controlled trials (RCTs) to assess the effect of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors on inflammatory biomarkers. Methods Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity. Results Thirty‐eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8.6 years) with a median (interquartile range) follow‐up of 16 (12–24) weeks. Meta‐analysis showed that SGLT2 inhibitors significantly improved adiponectin, interleukin‐6, tumour necrosis factor receptor‐1 (vs. placebo alone: standardized mean difference [SMD] 0.34 [95% confidence interval {CI} 0.23, 0.45], mean difference [MD] −0.85 pg/mL [95% CI −1.32, −0.38], SMD −0.13 [95% CI −0.20, −0.06], respectively), leptin and homeostatic model …

Antithrombotic therapy represents the cornerstone of the pharmacological treatment in patients with acute coronary syndrome (ACS). The optimal combination and duration of antithrombotic therapy is still matter of debate requiring a critical assessment of patient comorbidities, clinical presentation, revascularization modality, and/or optimization of medical treatment. The 2023 European Society of Cardiology (ESC) guidelines for the management of patients with ACS encompassing both patients with and without ST segment elevation ACS have been recently published. Shortly before, a European expert consensus task force produced guidance for clinicians on the management of antithrombotic therapy in patients with ACS as well as chronic coronary syndrome. The scope of this manuscript is to provide a critical appraisal of differences and similarities between the European consensus paper and the latest …

Purpose (the aim of the study): To identify the most effective and safest intra-articular interventions to reduce pain and improve physical function in patients with knee or hip OA.Methods: Data Sources: Electronic searches in the Cochrane Controlled Clinical Trial Register, regulatory agency websites, and ClinicalTrials. gov were performed (database inception to October, 2023).Study Selection: Randomized trials reported in English with≥ 100 patients per group that compared any intra-articular intervention to another intra-articular treatment, placebo or standard care.Main Outcomes and Measures: The prespecified primary outcome was pain intensity. We also assessed physical function and safety outcomes. Both pain intensity and physical function were evaluated at multiple time points: 2, 6, 12, 24 and 52 weeks after randomization.Data Extraction and Synthesis: Data were independently extracted by two …

ImportanceAbbreviated dual antiplatelet therapy (DAPT) reduces bleeding with no increase in ischemic events in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI).ObjectivesTo evaluate the association of sex with the comparative effectiveness of abbreviated vs standard DAPT in patients with HBR.Design, Setting, and PatientsThis prespecified subgroup comparative effectiveness analysis followed the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated vs Standard DAPT Regimen (MASTER DAPT) trial, a multicenter, randomized, open-label clinical trial conducted at 140 sites in 30 countries and performed from February 28, 2017, to December 5, 2019. A total of 4579 patients with HBR were randomized at 1 month after PCI to abbreviated or standard DAPT. Data were analyzed from July 1 to October 31 …

Background The use of assays detecting cytomegalovirus (CMV)–specific T cell–mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. Methods In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with …

The major aspects of the management of patients with acute coronary syndromes described in this European Society of Cardiology (ESC) Guideline are summarized in Figure 1.

RationaleDecompressive craniectomy (DC) is beneficial in people with malignant middle cerebral artery infarction. Whether DC improves outcome in spontaneous intracerebral haemorrhage (ICH) is unknown.AimTo determine whether DC without haematoma evacuation plus best medical treatment (BMT) in people with ICH decreases the risk of death or dependence at 6 months compared to BMT alone.Methods and designSWITCH is an international, multicentre, randomised (1:1), two-arm, open-label, assessor-blinded trial. Key inclusion criteria are age ⩽75 years, stroke due to basal ganglia or thalamic ICH that may extend into cerebral lobes, ventricles or subarachnoid space, Glasgow coma scale of 8–13, NIHSS score of 10–30 and ICH volume of 30–100 mL. Randomisation must be performed <66 h after onset and DC <6 h after randomisation. Both groups will receive BMT. Participants randomised to the …

In an era focused on value-based healthcare, the quality of healthcare and resource allocation should be underpinned by empirical evidence. Pragmatic clinical trials (pRCTs) are essential in this endeavor, providing randomized controlled trial (RCT) insights that encapsulate real-world effects of interventions. The rising popularity of pRCTs can be attributed to their ability to mirror real-world practices, accommodate larger sample sizes, and provide cost advantages over traditional RCTs. By harmonizing efficacy with effectiveness, pRCTs assist decision-makers in prioritizing interventions that have a substantial public health impact and align with the tenets of value-based health care. An international network for pRCT provides several advantages, including larger and diverse patient populations, access to a broader range of healthcare settings, sharing knowledge and expertise, and overcoming ethical and …

Objectives:Previous studies reported an association between higher driving pressure (∆ P) and increased mortality for different groups of mechanically ventilated patients. However, it remained unclear if sustained intervention on∆ P, in addition to traditional lung-protective ventilation, improves outcomes. We investigated if ventilation strategies limiting daily static or dynamic∆ P reduce mortality compared with usual care in adult patients requiring greater than or equal to 24 hours of mechanical ventilation.Design:For this comparative effectiveness study, we emulated pragmatic clinical trials using data from the Toronto Intensive Care Observational Registry recorded between April 2014 and August 2021. The per-protocol effect of the interventions was estimated using the parametric g-formula, a method that controls for baseline and time-varying confounding, as well as for competing events in the analysis of …

Purpose: To assess the effectiveness of different exercise modalities for knee and hip osteoarthritis pain and physical function in large, randomized trials.Methods: We conducted a systematic review with network and pairwise meta-analysis. We searched CENTRAL, MEDLINE, Embase and ClinicalTrials. gov from their inception until June 2022. We included randomized trials with≥ 100 patients per group, evaluating any exercise interventions (land or water-based) such as strengthening, flexibility or aerobic alone or a combination of programmes for the treatment of osteoarthritis. The prespecified primary outcome was pain intensity at 12-weeks and secondary was physical function. Outcomes were extracted at 6-, 12-, 24-and 52-weeks of follow-up. Two reviewers independently extracted outcome data and evaluated the risk of bias of included trials. We used Bayesian random-effects models for network and …

Background Low fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) has been associated with adverse clinical outcomes. Hitherto, this assessment has been independent of the epicardial vessel interrogated. Objectives This study sought to assess the predictive capacity of post-PCI FFR for target vessel failure (TVF) stratified by coronary artery. Methods We performed a systematic review and individual patient-level data meta-analysis of randomized clinical trials and observational studies with protocol-recommended post-PCI FFR assessment. The difference in post-PCI FFR between left anterior descending (LAD) and non-LAD arteries was assessed using a random-effect models meta-analysis of mean differences. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization. Results Overall, 3,336 vessels (n …

Importance Few interventions are proven to reduce total health care costs, and addressing cost-related nonadherence has the potential to do so. Objective To determine the effect of eliminating out-of-pocket medication fees on total health care costs. Design, Setting, and Participants This secondary analysis of a multicenter randomized clinical trial using a prespecified outcome took place across 9 primary care sites in Ontario, Canada (6 in Toronto and 3 in rural areas), where health care services are generally publicly funded. Adult patients (≥ 18 years old) reporting cost-related nonadherence to medicines in the past 12 months were recruited between June 1, 2016, and April 28, 2017, and followed up until April 28, 2020. Data analysis was completed in 2021. Interventions Access to a comprehensive list of 128 medicines commonly prescribed in ambulatory care with no out-of-pocket costs for 3 years vs usual …

BackgroundWe examined whether a school-based health center model improved academic achievement compared to usual care.MethodsThis was a quasi-experimental prospective cohort study. The primary outcome was an academic achievement. In addition, we analyzed sociodemographic characteristics and their relationship to academic achievement, and the wait time for a developmental assessment.ResultsThe differences in change of grades over time (from 2016/2017 to 2018/2019) were small for reading (–0.83, 95% CI –3.48, 1.82, p = 0.51), writing (–1.11, 95% CI –3.25, 1.03, p = 0.28), and math (0.06, 95% CI –3.08, 2.94, p = 0.98). The experimental arm’s average wait time for developmental assessment was 3.4 months.ConclusionIn this small, quasi-experimental prospective cohort study, we did not find evidence that our SBHC model improved academic achievement; however, the wait time at …

Objective:An understanding of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission in schools is important. It is often difficult, using epidemiological information alone, to determine whether cases associated with schools represent multiple introductions from the community or transmission within the school. We describe the use of whole genome sequencing (WGS) in multiple schools to investigate outbreaks of SARS-CoV-2 in the pre-Omicron period.Study Design:School outbreaks were identified for sequencing by local public health units based on multiple cases without known epidemiological links. Cases of SARS-CoV-2 from students and staff from 4 school outbreaks in Ontario underwent WGS and phylogenetic analysis. The epidemiological clinical cohort data and genomic cluster data are described to help further characterize these outbreaks.Results:A total of 132 positive SARS-CoV …

Multiple guidelines and consensus papers have addressed the role of antithrombotic strategies in patients with established coronary artery disease (CAD). Since evidence and terminology continue to evolve, the authors undertook a consensus initiative to guide clinicians to select the optimal antithrombotic regimen for each patient. The aim of this document is to provide an update for clinicians on best antithrombotic strategies in patients with established CAD, classifying each treatment option in relation to the number of antithrombotic drugs irrespective of whether the traditional mechanism of action is expected to mainly inhibit platelets or coagulation cascade. With the aim to reach comprehensiveness of available evidence, we systematically reviewed and performed meta-analyses by means of both direct and indirect comparisons to inform the present consensus document.

Aims To appraise all available antithrombotic treatments within or after 12 months following coronary revascularization and/or acute coronary syndrome in two network meta-analyses. Methods and results Forty-three (N = 189 261 patients) trials within 12 months and 19 (N = 139 086 patients) trials beyond 12 months were included for efficacy/safety endpoints appraisal. Within 12 months, ticagrelor 90 mg bis in die (b.i.d.) [hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.49–0.88], aspirin and ticagrelor 90 mg (HR, 0.85; 95% CI, 0.76–0.95), or aspirin, clopidogrel and rivaroxaban 2.5 mg b.i.d. (HR, 0.66; 95% CI, 0.51–0.86) were the only treatments associated with lower cardiovascular mortality, compared with aspirin and clopidogrel, without or with greater bleeding risk for the first and the other treatment options, respectively. Beyond 12 months, no strategy lowered mortality …

Objectives: The period of infancy and early childhood is widely recognized as a critical window for growth and development. Optimal infant and young child feeding practices promote physical health and lay a foundation for cognitive and academic achievement. Despite the well-documented benefits of breastfeeding, current breastfeeding practices lag behind national public health goals, and disparities in breastfeeding practices persist in the United States. Disparities in breastfeeding practices can be seen among families living in a rural county on the US-Mexico border in Arizona, where declines in exclusive breastfeeding occur in early infancy. The objective of this research is to characterize breastfeeding intent and describe the facilitators and barriers to breastfeeding experienced by Latine birthing parents in a rural county on the US-Mexico border of Arizona.Methods: Longitudinal, semi-structured interviews will be conducted with 25 pregnant Latine participants over 18 years of age at three time points: during their third trimester of pregnancy, within three weeks postpartum, and two months postpartum. Trained interviewers, bilingual in Spanish and English, will conduct these semi-structured interviews. Eligible pregnant participants will be recruited from clinics during their third trimester. The first semi-structured interview will include a socio-demographic questionnaire to provide additional background information on each participant. Key informant interviews will also be conducted with 25 healthcare and nutrition professionals, including OB/GYNs, Nurse-Midwives, Pediatricians, Certified Lactation Consultants, WIC staff, and Health Start …

BackgroundPatent foramen ovale (PFO)-associated strokes comprise approximately 10% of ischemic strokes in adults aged 18 to 60 years. Despite the overall beneficial effects of closure device placement in patients with a first PFO-associated cerebral ischemic event, the best treatment option for any individual patient encountered in routine clinical practice is often quite unclear.ObjectiveThe objective of this study was to evaluate the heterogeneity of treatment effect of PFO closure on stroke recurrence based on previously developed scoring systems.MethodsIndividual patient data were pooled from 6 randomized clinical trials that compared PFO closure plus medical therapy vs medical therapy alone in patients with PFO-associated stroke, which involved a total of 3740 participants. The trials were conducted worldwide from 2000 to 2017. Comparisons were made between PFO closure plus medical therapy vs medical therapy alone. Subgroup analyses used the Risk of Paradoxical Embolism (RoPE) score (a 10-point score in which higher scores reflect younger age and the absence of vascular risk factors) and the PFO-Associated Stroke Causal Likelihood (PASCAL) algorithm, which combines the RoPE score with high-risk PFO features (either an atrial septal aneurysm or a large shunt) to classify patients into 3 categories of causal relatedness:“unlikely,”“possible,” and “probable.” The main outcome was ischemic stroke.ResultsOver a median follow-up of 57 months (interquartile range, 24-64 months), 121 outcomes occurred in 3740 patients. The annualized incidence of stroke with medical therapy was 1.09%(95% CI, 0.88%-1.36%) and with …

BackgroundIt has been reported that ischemic risk is relatively higher but bleeding risk is vice versa in Europe as compared to those in Asia as known as “East Asian paradox”(Nat Rev Cardiol 2014). It has not yet been established whether such geographical difference between Europe and Asia influences the clinical outcome in patients with high bleeding risk (HBR) and biodegradable-polymer sirolimuseluting coronary stent (Ultimaster TM).MethodsIn the MASTER DAPT study, patients with HBR were randomly assigned to 1-month DAPT (abbreviated therapy) or to at least 3-month DAPT (standard therapy). The three ranked primary outcomes were net adverse clinical events (NACE; a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (MACCE; a composite of death from any cause, myocardial infarction, or stroke), and major or clinically …

AimsAnthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled …

Background There are limited data on the viral dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children. Understanding viral load changes over the course of illness and duration of viral shedding may provide insight into transmission dynamics to inform public health and infection-control decisions. Methods We conducted a prospective cohort study of children aged 18 years and younger with polymerase chain reaction–confirmed SARS-CoV-2 between 1 February 2022 and 14 March 2022. SARS-CoV-2 testing occurred on daily samples for 10 days; a subset of participants completed daily rapid antigen tests (RATs). Viral RNA trajectories were described in relation to symptom onset and resolution. The associations between both time since symptom onset/resolution and non-infectious viral load were evaluated using a Cox proportional hazards …

BackgroundMany inquiries, reports, and legislative reforms have been released in response to multiple waves of the COVID-19 pandemic nationally and provincially. The volume of analysis of the impact of COVID-19 on LTC presents a challenge to decision-makers to identify and prioritize key areas for improvement and action. This brief consolidates recommendations and offers evidence-supported lessons learned and opportunities for change.

ObjectiveTo evaluate the relationship between the timing of infant cereal introduction between 4 and 6 months of age and growth and dietary intake in later childhood.Study designA longitudinal cohort study was conducted among healthy children 0-10 years of age participating in The Applied Research Group for Kids cohort study between June 2008 and August 2019 in Toronto, Canada.ResultsOf 8943 children included, the mean (SD) age of infant cereal introduction was 5.7 (2.1) months. In the primary analysis, children who were introduced to infant cereal at 4 vs 6 months had 0.17 greater body mass index z score (95% CI 0.06-0.28; P = .002) and greater odds of obesity (OR 1.82; 95% CI 1.18-2.80; P = .006) at 10 years of age. In the secondary analysis, children who were introduced to infant cereal at 4 vs 6 months had 0.09 greater height-for-age z score (95% CI 0.04-0.15; P = .002) at 1 year of age, an …

New-generation drug-eluting stents (DES) strongly reduce restenosis and repeat revascularization compared with bare-metal stents (BMS) for percutaneous coronary intervention. There is residual uncertainty as to whether other prognostically relevant outcomes are affected by DES versus BMS concerning initial presentation (chronic coronary syndrome [CCS] vs acute coronary syndrome [ACS]). We performed an individual patient data meta-analysis of randomized trials comparing new-generation DES versus BMS (CRD42017060520). The primary outcome was the composite of cardiac death or myocardial infarction (MI). Outcomes were examined at maximum follow-up and with a 1-year landmark. Risk estimates are expressed as hazard ratio (HR) with 95% confidence interval (CI). A total of 22,319 patients were included across 14 trials; 7,691 patients (34.5%) with CCS and 14,628 patients (65.5%) with ACS …

Science is by definition iterative and collaborative, with the need for constant reappraisal and external validation, and cardiovascular research is no exception. 1 There has been a veritable democratization of research efforts, and it is a commonplace for the cardiovascular community to witness the conduct and publication of numerous clinical studies with similar scope and goals within a short time frame. The issue in such cases is how to inform ourselves and improve decisionmaking. In other words, which trials should be trusted? All of them? Only the largest ones? Mainly investigator-initiated or governmentfunded trials? Or those of higher methodological quality (Figure 1)?

Declarations of Interest: The declarations of interest of the members of the Ontario COVID-19 Science Advisory Table, its Working Groups, or its partners can be found at https://covid19-sciencetable. ca/. The declarations of interest of external authors can be found under additional resources at https://doi. org/10.47326/ocsat. 2022.03. 56.1. 0About Us: The Ontario COVID-19 Science Advisory Table is a group of scientific experts and health system leaders who evaluate and report on emerging evidence relevant to the COVID-19 pandemic, to inform Ontario’s response. Our mandate is to provide weekly summaries of relevant scientific evidence for the COVID-19 Health Coordination Table of the Province of Ontario, integrating information from existing scientific tables, Ontario’s universities and agencies, and the best global evidence. The Science Table summarizes its findings for the Health Coordination Table and the public in Science Briefs.

ObjectiveTo determine the effectiveness of TENS at relieving pain and improving physical function as compared to placebo TENS, and to determine its safety, in patients with knee osteoarthritis.MethodsMulti-centre, parallel, 1:1 randomized, double-blind, placebo-controlled clinical trial conducted in six outpatient clinics in Switzerland. We included 220 participants with knee osteoarthritis recruited between October 15, 2012, and October 15, 2014. Patients were randomized to 3 weeks of treatment with TENS (n = 108) or placebo TENS (n = 112). Our pre-specified primary endpoint was knee pain at the end of 3-weeks treatment assessed with the WOMAC pain subscale. Secondary outcome measures included WOMAC physical function subscale and safety outcomes.ResultsThere was no difference between TENS and placebo TENS in WOMAC pain at the end of treatment (mean difference −0.06; 95%CI -0.41 to 0 …

Wastewater-based surveillance of SARS-CoV-2 RNA has been implemented at building, neighbourhood, and city levels throughout the world. Implementation strategies and analysis methods differ, but they all aim to provide rapid and reliable information about community COVID-19 health states. A viable and sustainable SARS-CoV-2 surveillance network must not only provide reliable and timely information about COVID-19 trends, but also provide for scalability as well as accurate detection of known or unknown emerging variants. Emergence of the SARS-CoV-2 variant of concern Omicron in late Fall 2021 presented an excellent opportunity to benchmark individual and aggregated data outputs of the Ontario Wastewater Surveillance Initiative in Canada; this public health-integrated surveillance network monitors wastewaters from over 10 million people across major population centres of the province. We demonstrate that this coordinated approach provides excellent situational awareness, comparing favourably with traditional clinical surveillance measures. Thus, aggregated datasets compiled from multiple wastewater-based surveillance nodes can provide sufficient sensitivity (i.e., early indication of increasing and decreasing incidence of SARS-CoV-2) and specificity (i.e., allele frequency estimation of emerging variants) with which to make informed public health decisions at regional- and state-levels.

BackgroundThin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) have been shown to reduce target lesion failure (TLF) at one-year follow-up compared with durable polymer everolimus-eluting stents (DP-EES) among patients with acute coronary syndrome (ACS). The long-term clinical benefits of thin-strut BP-SES over DP-EES in ACS patients after complete degradation of the polymer coating remain uncertain.MethodsWe performed a post-hoc subgroup analysis of ACS patients included into the BIOSCIENCE randomized trial (NCT01443104). The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction or clinically indicated target lesion revascularization, at 5 years.ResultsAmong 2119 patients enrolled between March 2012 and May 2013, 1131 (53%) presented with ACS. The 5-year cumulative incidence of TLF was significantly lower in …

Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention‐to‐treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention‐to‐treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per‐protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time‐varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all …

CONTENTS Page 1 CONTENTS THE AMERICAN JOURNAL OF CARDIOLOGYâ VOL. 117, NO. 9 MAY 1, 2016 Coronary Artery Disease Prognostic Utility of Calcium Scoring as an Adjunct to Stress Myocardial Perfusion Scintigraphy in End-Stage Renal Disease ..............................1387 William E. Moody, Erica LS Lin, Matthew Stoodley, David McNulty, Louise E. Thomson, Daniel S. Berman, Nicola C. Edwards, Benjamin Holloway, Charles J. Ferro, Jonathan N. Townend, and Richard P. Steeds, On behalf of the Birmingham Cardio-Renal Group Usefulness of High-Sensitivity Cardiac Troponin T for the Identification of Outlier Patients With Diffuse Coronary Atherosclerosis and Low-Risk Factors.......................................................1397 Marco Magnoni, Serge Masson, Daniele Andreini, Tiziano Moccetti, Maria Grazia Modena, Mauro Canestrari, Sergio Berti, Giancarlo Casolo, Domenico Gabrielli, Paolo Marraccini, Gianluca …

Objective To evaluate the effectiveness and safety of viscosupplementation for pain and function in patients with knee osteoarthritis.Design Systematic review and meta-analysis of randomised trials.Data sources Searches were conducted of Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to 11 September 2021. Unpublished trials were identified from the grey literature and trial registries.Eligibility criteria for study selection Randomised trials comparing viscosupplementation with placebo or no intervention for knee osteoarthritis treatment.Main outcome measures The prespecified primary outcome was pain intensity. Secondary outcomes were function and serious adverse events. Pain and function were analysed as standardised mean differences (SMDs). The prespecified minimal clinically important between group difference was −0.37 SMD. Serious …

Background In some randomized clinical trials, transradial access (TRA) compared with transfemoral access (TFA) was associated with lower mortality in patients with coronary artery disease undergoing invasive management. We analyzed the effects of TRA versus TFA across multicenter randomized clinical trials and whether these associations are modified by patient or procedural characteristics. Methods We performed an individual patient data meta-analysis of multicenter randomized clinical trials comparing TRA with TFA among patients undergoing coronary angiography with or without percutaneous coronary intervention. The primary outcome was all-cause mortality and the co–primary outcome was major bleeding at 30 days. The primary analysis was conducted by 1-stage mixed-effects models on the basis of the intention-to-treat cohort. The effect of access site on mortality and major bleeding was …

Introduction: Patent foramen ovale (PFO) closure is effective for secondary stroke prevention in well selected patients. After device implantation some patients have residual shunting. There was no impact of incomplete closure on recurrent stroke risk in any of the trials but outcome rates are low with little power to detect an effect. Hypothesis: Patients with residual shunts after PFO closure have more recurrent strokes than those with complete elimination of shunting. Methods: We pooled individual patient data from 5 of 6 randomized clinical trials comparing medical therapy to PFO closure + medical therapy. Residual shunt data were not available for 1 trial. This analysis only includes PFO closure subjects. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated with Cox proportional hazards regression, adjusted for age, sex, coronary disease, diabetes, hypertension, hyperlipidemia, prior stroke/TIA …

Aim To characterize the association between diabetes and transfusion and clinical outcomes in cardiac surgery, and to evaluate whether restrictive transfusion thresholds are harmful in these patients. Materials and Methods The multinational, open‐label, randomized controlled TRICS‐III trial assessed a restrictive transfusion strategy (haemoglobin [Hb] transfusion threshold <75 g/L) compared with a liberal strategy (Hb <95 g/L for operating room or intensive care unit; or <85 g/L for ward) in patients undergoing cardiac surgery on cardiopulmonary bypass with a moderate‐to‐high risk of death (EuroSCORE ≥6). Diabetes status was collected preoperatively. The primary composite outcome was all‐cause death, stroke, myocardial infarction, and new‐onset renal failure requiring dialysis at 6 months. Secondary outcomes included components of the composite outcome at 6 months, and transfusion and clinical …

Background: The Portfolio Diet, or Dietary Portfolio, is a therapeutic dietary pattern that combines cholesterol-lowering foods to manage dyslipidemia for the prevention of cardiovascular disease. To translate the Portfolio Diet for primary care, we developed the PortfolioDiet. app as a patient and physician educational and engagement tool for PCs and smartphones. The PortfolioDiet. app is currently being used as an add-on therapy to the standard of care (usual care) for the prevention of cardiovascular disease in primary care. To enhance the adoption of this tool, it is important to ensure that the PortfolioDiet. app meets the needs of its target end users.Objective: The main objective of this project is to undertake user testing to inform modifications to the PortfolioDiet. app as part of ongoing engagement in quality improvement (QI).Methods: We undertook a 2-phase QI project from February 2021 to September 2021. We recruited users by convenience sampling. Users included patients, family physicians, and dietitians, as well as nutrition and medical students. For both phases, users were asked to use the PortfolioDiet. app daily for 7 days. In phase 1, a mixed-form questionnaire was administered to evaluate the users’ perceived acceptability, knowledge acquisition, and engagement with the PortfolioDiet. app. The questionnaire collected both quantitative and qualitative data, including 2 open-ended questions. The responses were used to inform modifications to the PortfolioDiet. app. In phase 2, the System Usability Scale was used to assess the usability of the updated PortfolioDiet. app, with a score higher than 70 being considered acceptable.

Aims The aim of this study was to investigate the efficacy and safety of ticagrelor monotherapy in patients undergoing percutaneous coronary intervention (PCI) stratified according to the baseline white blood cell (WBC) count. Methods and results This is a post hoc analysis of the GLOBAL LEADERS trial, a multi-centre, open-label, randomized all-comer trial in patients undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual anti-platelet therapy [DAPT]) with the reference strategy (12-month aspirin monotherapy following 12-month DAPT). Patients were stratified into two WBC groups, either < or ≥median WBC count of 7.8 × 109 cells/L (lower or higher WBC group, respectively). The primary endpoint was a composite of all-cause mortality or new Q-wave myocardial infarction at 2 years. Of 14 576 patients included in the …

ImportanceWearing a face mask in school can reduce SARS-CoV-2 transmission but it may also lead to increased hand-to-face contact, which in turn could increase infection risk through self-inoculation.ObjectiveTo evaluate the effect of wearing a face mask on hand-to-face contact by children while at school.Design, Setting, and ParticipantsThis prospective randomized clinical trial randomized students from junior kindergarten to grade 12 at 2 schools in Toronto, Ontario, Canada, during August 2020 in a 1:1 ratio to either a mask or control class during a 2-day school simulation. Classes were video recorded from 4 angles to accurately capture outcomes.InterventionsParticipants in the mask arm were instructed to bring their own mask and wear it at all times. Students assigned to control classes were not required to mask at any time (grade 4 and lower) or in the classroom where physical distancing could be …

ImportanceFew studies have examined the association between underweight in the first 2 years and growth in later childhood in high-income countries.ObjectiveTo evaluate the associations of underweight in the first 2 years of life with body mass index (calculated as weight in kilograms divided by height in meters squared)zscore (zBMI), weight-for-agezscore (WAZ), and height-for-agezscore (HAZ) from ages 2 to 10 years.Design, Setting, and ParticipantsThis prospective cohort study was conducted between February 2008 to September 2020 in The Applied Research Group for Kids! practice-based research network in Toronto, Canada. Participants included healthy children aged 0 to 10 years. Data were analyzed from October 2020 to December 2021.ExposuresUnderweight (ie, zBMI less than −2, per the World Health Organization) in the first 2 years of life.Main Outcomes and MeasuresThe primary outcome was …

BackgroundCerebral protection remains the cornerstone of successful aortic surgery; however, there is no consensus as to the optimal strategy.ObjectiveTo compare the safety and efficacy of innominate to axillary artery cannulation for delivering antegrade cerebral protection during proximal aortic arch surgery.MethodsThis randomized controlled trial (The Aortic Surgery Cerebral Protection Evaluation CardioLink-3 Trial, ClinicalTrials.gov Identifier: NCT02554032), conducted across 6 Canadian centers between January 2015 and June 2018, allocated 111 individuals to innominate or axillary artery cannulation. The primary safety outcome was neuroprotection per the appearance of new severe ischemic lesions on the postoperative diffusion-weighted-magnetic resonance imaging. The primary efficacy outcome was the difference in total operative time. Secondary outcomes included 30-day all-cause mortality and …

The True Infection Rate (TIR) in the whole population of each country and the Infection Fatality Rate (IFR) for coronavirus disease 2019 (COVID-19) are unknown although they are important parameters. We devised a simple method to infer TIR and IFR based on the open data. The prevalence rate of the polymerase chain reaction (PCR) tests among the population (Examination Rate; ER) and the positive rate of PCR tests (Infection Rate; IR) for 66 countries were picked up at a website 5 times from April 10th to June 13th, 2020, and the trajectory of each country was drawn over the IR vs. ER plot. IR and ER showed a strong negative correlation for some countries, and TIR was estimated by extrapolating the regression line when the correlation coefficient was between-0.99 and-1. True/Identified Case Ratio (TICR) and IFR were also calculated using the estimated TIR. The estimated TIR well coincided with local antibody surveys. Estimated IFR took on a wide range of values up to 10% generally high in the Western countries. The estimated IFR of Singapore was very low (0.018%), which may be related to the reported gene mutation causing the attenuation of the viral virulence.

Declarations of Interest: The declarations of interest of the members of the Ontario COVID-19 Science Advisory Table, its Working Groups, or its partners can be found at https://covid19-sciencetable. ca/. The declarations of interest of external authors can be found under additional resources at https://doi. org/10.47326/ocsat. 2022.03. 57.1. 0About Us: The Ontario COVID-19 Science Advisory Table is a group of scientific experts and health system leaders who evaluate and report on emerging evidence relevant to the COVID-19 pandemic, to inform Ontario’s response. Our mandate is to provide weekly summaries of relevant scientific evidence for the COVID-19 Health Coordination Table of the Province of Ontario, integrating information from existing scientific tables, Ontario’s universities and agencies, and the best global evidence. The Science Table summarizes its findings for the Health Coordination Table and the public in Science Briefs.

BackgroundLichen sclerosus (LS) is a chronic inflammatory skin disease that mostly affects the anogenital region of women and lowers patients’ quality of life. Current standard treatment of LS is topical steroids.ObjectiveTo evaluate the efficacy of topical progesterone 8% ointment and compare to standard therapy with topical clobetasol propionate 0.05% in premenopausal women presenting with previously untreated early onset LS.Study designRandomized, double-blind, 2-arm, single center superiority trial in premenopausal women with histologically confirmed vulvar LS who were randomized in a 1:1 ratio to receive clobetasol propionate 0.05% ointment or progesterone 8% ointment. The primary outcome was the clinical severity LS score after 12 weeks, which consists of six clinical features assessed by the physician. Secondary outcomes were the symptom severity LS score, which consists of three symptoms …

Aims The five-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally adjudicated bleeding endpoints. Methods and results The PRECISE-DAPT was calculated in 14 928 and 7134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict Bleeding Academic Research Consortium 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference …

Background: Although von Willebrand disease (VWD) is inherited by men and women equally, women are more likely to experience bleeding symptoms due to the challenges of menstruation and childbirth. Heavy menstrual bleeding (HMB) is the most common symptom observed in women and girls with VWD, and increases risk of iron deficiency anemia, blood transfusion, hospitalization and decreased health-related quality of life. While replacement therapy with von Willebrand factor (VWF) is recommended for prophylaxis in patients with VWD with severe and frequent bleeding, recommendations on its use for prophylaxis of HMB are limited due the lack of clinical trial data.Aims: The EMPOWER pilot trial will determine the feasibility of the trial design, as well as explore assay sensitivity to inform the determination of the primary outcome for the definitive randomized trial which will evaluate the effect of prophylaxis …

Introduction Overdose education and naloxone distribution (OEND) programmes equip and train people who are likely to witness an opioid overdose to respond with effective first aid interventions. Despite OEND expansion across North America, overdose rates are increasing, raising questions about how to improve OEND programmes. We conducted an iterative series of codesign stakeholder workshops to develop a prototype for take‐home naloxone (THN)‐kit (i.e., two doses of intranasal naloxone and training on how to administer it). Methods We recruited people who use opioids, frontline healthcare providers and public health representatives to participate in codesign workshops covering questions related to THN‐kit prototypes, training on how to use it, and implementation, including refinement of design artefacts using personas and journey maps. Completed over 9 months, the workshops were audio …

Background Several studies have suggested that proton pump inhibitors (PPIs) may reduce the antiplatelet effects of clopidogrel and/or aspirin, possibly leading to cardiovascular events. Aims We aimed to investigate the association between PPI and clinical outcomes in patients treated with ticagrelor monotherapy or conventional antiplatelet therapy after percutaneous coronary intervention (PCI). Methods This is a subanalysis of the randomized GLOBAL LEADERS trial, comparing the experimental antiplatelet arm (23‐month ticagrelor monotherapy following 1‐month dual antiplatelet therapy [DAPT]) with the reference arm (12‐month aspirin monotherapy following 12‐month DAPT) after PCI. Patient‐oriented composite endpoints (POCEs: all‐cause mortality, myocardial infarction, stroke, or repeat revascularization) and its components were assessed stratified by PPI use as a time‐dependent covariate in …

Health professionals are encouraged to take the ESC/EACTS Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies. However, the ESC/EACTS Guidelines do not override in any way whatsoever the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient or the patient’s caregiver where appropriate and/or necessary. It is also the healthcare professional’s responsibility to verify the rules and regulations applicable in each country to drugs and devices at the time of prescription.

BackgroundLate mortality risk in sepsis-survivors persists for years with high readmission rates and low quality of life. The present study seeks to link the clinical sepsis-survivors heterogeneity with distinct biological profiles at ICU discharge and late adverse events using an unsupervised analysis. MethodsIn the original FROG-ICU prospective, observational, multicenter study, intensive care unit (ICU) patients with sepsis on admission (Sepsis-3) were identified (N = 655). Among them, 467 were discharged alive from the ICU and included in the current study. Latent class analysis was applied to identify distinct sepsis-survivors clinical classes using readily available data at ICU discharge. The primary endpoint was one-year mortality after ICU discharge.ResultsAt ICU discharge, two distinct subtypes were identified (A and B) using 15 readily available clinical and biological variables. Patients assigned to subtype B …

ImportanceThe Patent Foramen Ovale (PFO)–Associated Stroke Causal Likelihood classification system combines information regarding noncardiac patient features (vascular risk factors, infarct topography) and PFO features (shunt size and presence of atrial septal aneurysm [ASA]) to classify patients into 3 validated categories of responsiveness to treatment with PFO closure. However, the distinctive associations of shunt size and ASA, alone and in combination, have not been completely delineated.ObjectiveTo evaluate the association of PFO closure with stroke recurrence according to shunt size and/or the presence of an ASA.Design, Setting, and ParticipantsPooled individual patient data from 6 randomized clinical trials conducted from February 2000 to October 2017 that compared PFO closure with medical therapy. Patients in North America, Europe, Australia, Brazil, and South Korea with PFO-associated …

BackgroundCam and pincer morphologies are associated with limited internal rotation. However, the routine clinical examination for hip rotation has limited reliability. A more standardized method of measuring hip rotation might increase test-retest and interobserver reliability and might be useful as a screening test to detect different hip morphologies without the need for imaging. We developed an examination chair to standardize the measurement of internal hip rotation, which improved interobserver reliability. However, the diagnostic test accuracy for this test is unknown.

The True Infection Rate (TIR) in the whole population of each country and the Infection Fatality Rate (IFR) for coronavirus disease 2019 (COVID-19) are unknown although they are important parameters. We devised a simple method to infer TIR and IFR based on the open data. The prevalence rate of the polymerase chain reaction (PCR) tests among the population (Examination Rate; ER) and the positive rate of PCR tests (Infection Rate; IR) for 66 countries were picked up at a website 5 times from April 10th to June 13th, 2020, and the trajectory of each country was drawn over the IR vs. ER plot. IR and ER showed a strong negative correlation for some countries, and TIR was estimated by extrapolating the regression line when the correlation coefficient was between -0.99 and -1. True/Identified Case Ratio (TICR) and IFR were also calculated using the estimated TIR. The estimated TIR well coincided with local …

A recent meta-analysis assessed short-term DAPT (1 to 3 months) versus standard DAPT (12 to 24 months) and reported lower bleeding risks with similar ischemic events using the abbreviated DAPT duration. 3 More recent evidence accumulated since then for even shorter duration (1-month DAPT) has shown promising results.[...] we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the safety and efficacy of 1-month DAPT in this population. Newer-generation stents probably play a role in mitigating the ischemic events after PCI (stent thrombosis, in-stent restenosis, and so on). 3 Thereby, shorter DAPT duration led to fewer bleeding events with retention of ischemic benefits.[...] in patients who underwent PCI, 1-month DAPT followed by SAPT might be a safe and effective alternative compared with standard DAPT (≥ 3 months).

The clinical implications of hypertension in addition to a high prevalence of both uncontrolled blood pressure and medication nonadherence promote interest in developing device-based approaches to hypertension treatment. The expansion of device-based therapies and ongoing clinical trials underscores the need for consistency in trial design, conduct, and definitions of clinical study elements to permit trial comparability and data poolability. Standardizing methods of blood pressure assessment, effectiveness measures beyond blood pressure alone, and safety outcomes are paramount. The Hypertension Academic Research Consortium (HARC) document represents an integration of evolving evidence and consensus opinion among leading experts in cardiovascular medicine and hypertension research with regulatory perspectives on clinical trial design and methodology. The HARC document integrates the …

Aims Myocardial injury (MINJ) in Coronavirus disease 2019 (COVID-19) identifies individuals at high mortality risk but its clinical relevance is less well established for Influenza and no comparative analyses evaluating frequency and clinical implications of MINJ among hospitalized patients with Influenza or COVID-19 are available. Methods and results Hospitalized adults with laboratory confirmed Influenza A or B or COVID-19 underwent highly sensitive cardiac T Troponin (hs-cTnT) measurement at admission in four regional hospitals in Canton Ticino, Switzerland. MINJ was defined as hs-cTnT >14 ng/L. Clinical, laboratory and outcome data were retrospectively collected. The primary outcome was mortality up to 28 days. Cox regression models were used to assess correlations between admission diagnosis, MINJ, and mortality. Clinical correlates of MINJ in both viral …

Background Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case. Methods This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation. Participants will be individuals aged > 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote …

Declarations of Interest: The declarations of interest of the members of the Ontario COVID-19 Science Advisory Table, its Working Groups, or its partners can be found at https://covid19-sciencetable. ca/. The declarations of interest of external authors can be found under additional resources at https://doi. org/10.47326/ocsat. 2021.02. 52.1. 0About Us: The Ontario COVID-19 Science Advisory Table is a group of scientific experts and health system leaders who evaluate and report on emerging evidence relevant to the COVID-19 pandemic, to inform Ontario’s response. Our mandate is to provide weekly summaries of relevant scientific evidence for the COVID-19 Health Coordination Table of the Province of Ontario, integrating information from existing scientific tables, Ontario’s universities and agencies, and the best global evidence. The Science Table summarizes its findings for the Health Coordination Table and the public in Science Briefs.

Wastewater testing for SARS-CoV-2 is relatively new; however, it builds on existing public health surveillance infrastructure. There is a limited but growing evidence base for its use, despite notable interpretation challenges. Wastewater testing results have helped to inform public health policy and interventions during the COVID-19 pandemic in Ontario and other jurisdictions. Wastewater testing for SARS-CoV-2 is useful for early detection of outbreaks and surges as well as population-wide surveillance of COVID-19 that is complementary to clinical testing. Further, it offers an efficient means of SARS-CoV-2 surveillance for specific settings such as correctional facilities, shelters, and university residences. Wastewater testing can also be used for the detection and monitoring of variants of concern (VOCs).

Background This study aimed to assess the effectiveness of sodium‐glucose cotransporter 2 inhibitors in reducing the incidence of mortality and cardiovascular outcomes in adults with type 2 diabetes. Methods and Results We conducted a Bayesian meta‐analysis of randomized controlled trials comparing sodium‐glucose cotransporter 2 inhibitors with placebo. We used meta‐regression to examine the association between treatment effects and control group event rates as measures of cardiovascular baseline risk. Fifty‐three randomized controlled trials were included in our synthesis. Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all‐cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63–0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69–1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72–1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61–1.00 …

Background The optimal duration of antiplatelet therapy (APT) in patients at high bleeding risk with or without oral anticoagulation (OAC) after coronary stenting remains unclear. Methods In the investigator-initiated, randomize, open-label MASTER DAPT trial (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Standard DAPT Regimen), 4579 patients at high bleeding risk were randomized after 1-month dual APT to abbreviated or nonabbreviated APT strategies. Randomization was stratified by concomitant OAC indication. In this subgroup analysis, we report outcomes of populations with or without an OAC indication. In the population with an OAC indication, patients changed immediately to single APT for 5 months (abbreviated regimen) or continued ≥2 months of dual APT and single APT thereafter (nonabbreviated regimen). Patients …

Shelter-in-place mandates and closure of nonessential businesses have been central to COVID19 response strategies including in Toronto, Canada. Approximately half of the working population in Canada are employed in occupations that do not allow for remote work suggesting potentially limited impact of some of the strategies proposed to mitigate COVID-19 acquisition and onward transmission risks and associated morbidity and mortality. We compared per-capita rates of COVID-19 cases and deaths from January 23, 2020 to January 24, 2021, across neighborhoods in Toronto by proportion of the population working in essential services. We used person-level data on laboratory-confirmed COVID-19 community cases and deaths, and census data for neighborhood-level attributes. Cumulative per-capita rates of COVID-19 cases and deaths were 3.3-fold and 2.5-fold higher, respectively, in neighborhoods with …

Identifying febrile children at risk of sepsis in low-resource settings can improve survival, but recognition triage tools are lacking. Here we test the hypothesis that measuring circulating markers of immune and endothelial activation may identify children with sepsis at risk of all-cause mortality. In a prospective cohort study of 2,502 children in Uganda, we show that Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) measured at first clinical presentation, had high predictive accuracy for subsequent in-hospital mortality. sTREM-1 had the best performance, versus 10 other markers, with an AUROC for discriminating children at risk of death of 0.893 in derivation (95% CI 0.843–0.944) and 0.901 in validation (95% CI 0.856–0.947) cohort. sTREM-1 cutoffs corresponding to a negative likelihood ratio (LR) of 0.10 and a positive LR of 10 classified children into low (1,306 children, 53.1%), intermediate (942 …

Background New‐generation drug‐eluting stents (DES) reduce target‐vessel revascularization compared with bare‐metal stents (BMS), and recent data suggest that DES have the potential to decrease the risk of myocardial infarction and cardiovascular mortality. We evaluated the treatment effect of DES versus BMS according to the target artery (left anterior descending [LAD] and/or left main [LM] versus other territories [no‐LAD/LM]). Methods and Results The Coronary Stent Trialist (CST) Collaboration gathered individual patient data of randomized trials of DES versus BMS for the treatment of coronary artery disease. The primary outcome was the composite of cardiac death or myocardial infarction. Hazard ratios (HRs) with 95% CIs were derived from a 1‐stage individual patient data meta‐analysis. We included 26 024 patients across 19 trials: 13 650 (52.4%) in the LAD/LM and 12 373 (47.6%) in the no‐LAD …

Background Pulmonary endothelial injury and microcirculatory thromboses likely contribute to hypoxemic respiratory failure, the most common cause of death, in patients with COVID‐19. Randomized controlled trials (RCTs) suggest differences in the effect of therapeutic heparin between moderately and severely ill patients with COVID‐19. We did a systematic review and meta‐analysis of RCTs to determine the effects of therapeutic heparin in hospitalized patients with COVID‐19. Methods We searched PubMed, Embase, Web of Science, medRxiv, and medical conference proceedings for RCTs comparing therapeutic heparin with usual care, excluding trials that used oral anticoagulation or intermediate doses of heparin in the experimental arm. Mantel‐Haenszel fixed‐effect meta‐analysis was used to combine odds ratios (ORs). Results and Conclusions There were 3 RCTs that compared therapeutic heparin to …

BackgroundRates of opioid-related harm, particularly fatal overdose, have increased significantly in Ontario during the COVID-19 pandemic. Reducing the burden of opioid-related harm among people who use drugs (PWUD) will require systematic interventions and ongoing evaluation of the effectiveness of these interventions.

The systematic review included literature up to May 3, 2020. Seven articles, including four preprints, described the comparison of the risk of SARS-CoV-2 transmission between far and short physical distancing. Further physical distancing was associated with a lower risk of SARS-CoV-2 transmission (relative risk [RR] 0· 15 compared with shorter physical distancing, 95% CI 0· 03–0· 73, I²= 59%; appendix).We followed up on the status of the four preprints and found that one of them2 was published online on May 1, 2020, 3 before the search cutoff date. The published version used a larger dataset (n= 227 vs n= 83 in the preprint), and the risk of SARS-CoV-2 transmission was almost equal between the physical distancing groups (RR 0· 99 vs RR 0· 55 in the preprint). We updated the meta-analysis, replacing the results from the preprint by the corresponding published study. 3 The association between physical …

Issue Date: 2021 Publisher: OXFORD UNIV PRESS Source: EUROPEAN HEART JOURNAL, 42, p. 2998-2998 Document URI: http://hdl. handle. net/1942/36273 ISSN: 0195-668X e-ISSN: 1522-9645 ISI#: WOS: 000720456903299 Category: M Type: Journal Contribution

Background The appropriate duration of dual antiplatelet therapy in patients at high risk for bleeding after the implantation of a drug-eluting coronary stent remains unclear. Methods One month after they had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent, we randomly assigned patients at high bleeding risk to discontinue dual antiplatelet therapy immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy). The three ranked primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding; cumulative incidences were assessed at 335 days. The first two outcomes were assessed for noninferiority in the …

The 2021-2022 academic year has already begun and there has been significant media coverage and discussion regarding how schools should operate. Vaccination rates and the emergence of novel and more contagious variants of concern, particularly the Delta variant, have shaped the evolution of the COVID-19 pandemic in Canada.This Issue Note answers the following question: For the 2021-2022 academic year, what are the key considerations to use in determining which public health measures are to be kept (eg masking) or introduced,(eg regular self-testing) in kindergarten, elementary, secondary, and postsecondary schools?

Introduction: Patent foramen ovale (PFO)-associated strokes account for ~10% of ischemic strokes in adults aged 18-60. Despite overall beneficial effects of device closure on stroke recurrence risk, the best treatment option for any individual patient is often unclear. Methods: We pooled individual participant-level data from all 6 RCTs comparing PFO closure with percutaneous devices plus medical therapy vs medical therapy alone. The primary outcome was recurrent ischemic stroke. We used Cox proportional hazards models to estimate adjusted HRs, with study-specific baseline hazards and a fixed treatment effect. Pre-specified primary subgroup analyses used the Risk of Paradoxical Embolism (RoPE) Score (a 10 point score with higher scores reflecting younger age and absence of vascular risk factors) and the PFO-Associated Stroke Causal Likelihood (PASCAL) algorithm, a classification system that combines …

Aims Acute kidney injury (AKI) is a critical complication among patients with acute coronary syndrome (ACS) undergoing invasive management. The value of adjunctive antithrombotic strategies, such as bivalirudin or unfractionated heparin (UFH) on the risk of AKI is unclear. Methods and results Among 7213 patients enrolled in the MATRIX-Antithrombin and Treatment Duration study, 128 subjects were excluded due to incomplete information on serum creatinine (sCr) or end-stage renal disease on dialysis treatment. The primary endpoint was AKI defined as an absolute (>0.5 mg/dL) or a relative (>25%) increase in sCr. AKI occurred in 601 patients (16.9%) treated with bivalirudin and 616 patients (17.4%) treated with UFH [odds ratio (OR): 0.97; 95% confidence interval (CI): 0.85–1.09; P = 0.58]. A >25% sCr increase was observed in 597 patients (16.8%) with bivalirudin and …

Ontario long‐term care (LTC) home residents have experienced disproportionately high morbidity and mortality, both from COVID‐19 and from the conditions associated with the COVID‐19 pandemic. As of July 10, 2021, a total of 3,975 LTC home residents have died of COVID‐19, totaling 43.0% of all 9,245 COVID‐19 deaths in Ontario. The most important risk factors for whether a LTC home will experience an outbreak is the daily incidence of SARS‐CoV‐2 infections in the communities surrounding the home and the occurrence of staff infections. The most important risk factors for the magnitude of an outbreak and the number of resulting resident deaths are older design, chain ownership, and crowding. Many Ontario LTC home residents have experienced severe and potentially irreversible physical, cognitive, psychological, and functional declines as a result of precautionary public health interventions imposed …

We appreciate the interest on the 2020 European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation (NSTE-ACS). 1 The updated new guideline has considered the landmark trials published within the last 5 years to formulate updated, practical, and new recommendations. As such, the chairmen and the Task Force of the ESC guidelines support any scientific discussion on the guidelines, an essential component of their dissemination and implementation in clinical practice. The guidelines were presented at ESC Congress 2020, but the virtual nature of the meeting has limited the options of discussion. Among them is a debate on the class IIa level of evidence B recommendation on preference of prasugrel over ticagrelor for patients undergoing percutaneous coronary intervention (PCI) and to not recommend …

Background Bleeding is the principal safety concern of antithrombotic therapy and occurs frequently among patients with coronary artery disease (CAD). Aims We aim to evaluate the prognostic impact of bleeding on mortality compared with that of myocardial infarction (MI) in patients with CAD. Methods We searched Medline and Embase for studies that included patients with CAD and that reported both, the association between the occurrence of bleeding and mortality, and between the occurrence of MI and mortality within the same population. Adjusted hazard ratios (HRs) for mortality associated with bleeding and MI were extracted and ratio of hazard ratios (rHRs) were pooled by using inverse variance weighted random effects meta-analyses. Early events included periprocedural or within 30-day events after revascularization or acute coronary syndrome …

Background The prevalence of atrial fibrillation (AF) is high in older patients. The present study aimed to estimate the age and sex specific prevalence of clinical and screen-detected atrial fibrillation (AF) in hospitalized patients. Methods The STAR-FIB cohort study was a prospective cohort study recruiting participants from a large source population of hospitalized patients aged 65–84 years. The estimated size of the source population was 26,035 (95% CI 25,918–26,152), and 795 consenting patients without clinical AF were included in the cohort study after stratification by sex and age (49.2% females; mean age 74.7 years). Patients in the cohort study underwent three seven-day Holter ECGs in intervals of two months to screen for AF. Results In the source population, the estimated prevalence of clinical AF was 22.2% (95% CI 18.4–26.1), 23.8% for males (95% CI 20.9–26.6) and 19.8% for females (95% CI 17.3–22.4; p for difference between sexes, 0.004). There was a linear trend for an increase in the prevalence of clinical AF with increasing age, overall and in both sexes. In the cohort study, AF was newly diagnosed in 38 patients, for an estimated prevalence of screen-detected AF of 4.9% overall (95% CI 3.3–6.6), 5.5% in males (95% CI 3.2–7.8) and 4.0% in females (95% CI 2.0–6.0; p for difference between sexes, 0.041). The estimated prevalence of screen-detected AF in the source population was 3.8% overall, 4.2% in males and 3.2% in females. Conclusion In a large hospital-based patient population aged 65–84 years, the prevalence of clinical AF and of screen-detected AF was 22.2% and 3.8%, respectively, and significantly higher in …

L’année scolaire 2021-2022 a déjà commencé. Les élèves, les enseignants et le personnel fréquentent les écoles maternelles, primaires, secondaires et postsecondaires du Canada pour un apprentissage en présentiel.

BackgroundOpioid overdose epidemic is a public health crisis that is impacting communities around the world. Overdose education and naloxone distribution programs equip and train lay people to respond in the event of an overdose. We aimed to design an open-access naloxone kit and ultra-brief education session for use in point-of-care settings.MethodsWe hosted a multi-stakeholder co-design workshop to elicit suggestions for the kit and education session. We recruited people with lived experience of opioid overdose, community representatives, and other stakeholders from family practice, emergency medicine, addictions medicine, and public health to participate in a one-day facilitated co-design discussion wherein large and small group discussions were audio-recorded, transcribed and analysed using thematic approaches.ResultsA total of twenty four participants participated in the multi-stakeholder workshop from five stakeholder groups including geographic and setting diversity. Collaborative dialogue and shared storytelling which revealed seven design considerations: recognizing overdose, how much naloxone, impact of stigma, legal risk of responding, position as conventional first aid, friends and family as responders, support to call 911.ConclusionTo create an open access kit and ultra-brief education session for distribution in emergency departments, family practice and substance use treatment services, stigma is a central design consideration. Design choices that reference the iconography, type, and form of materials associated with first aid have the potential to satisfy the need to de-stigmatize overdose response.

Objectives To determine the effect of therapeutic anticoagulation, with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram), compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death up to 28 days. Trial design Open-label, parallel, 1:1, phase 3, 2-arm randomized controlled trial Participants The study population includes hospitalized adults admitted for COVID-19 prior to the development of critical illness. Excluded individuals are those where the bleeding risk or risk of transfusion would generally be considered unacceptable, those already therapeutically anticoagulated and those who have …

ImportancePostoperative atrial fibrillation (POAF) occurring after cardiac surgery is associated with adverse outcomes. Whether POAF persists beyond discharge is not well defined.ObjectiveTo determine whether continuous cardiac rhythm monitoring enhances detection of POAF among cardiac surgical patients during the first 30 days after hospital discharge compared with usual care.Design, Setting, and ParticipantsThis study is an investigator-initiated, open-label, multicenter, randomized clinical trial conducted at 10 Canadian centers. Enrollment spanned from March 2017 to March 2020, with follow-up through September 11, 2020. As a result of the COVID-19 pandemic, enrollment stopped on July 17, 2020, at which point 85% of the proposed sample size was enrolled. Cardiac surgical patients with CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, prior stroke or transient …

The authors regret to inform that we have identified a computational error in our recent publication,“Mixed methods feasibility study for the Surviving Opioid Overdose with Naloxone Education and Resuscitation (SOONER) Trial”. This error was identified in the process of preparing another manuscript arising from the same study, which used similar statistical coding. In brief, our statistical team identified that there was a coding error in R involving the labelling of categorical variables. The issue has now been corrected.Our clinical trials unit has responded to this error by initiating a thorough investigation and quality assurance process including a root-cause analysis to determine how this occurred and ensure that this kind of error does not recur. In addition, all other analyses and reported statistics in this paper have been reviewed by an independent senior statistician to ensure that they are correct. The error identified affects Table 2 and Table 3 of the published manuscript. Revised versions of these tables are appended below. The authors would like to apologise for any inconvenience caused.

Objectives This study aimed to assess the predictive ability of the Global Registry of Acute Coronary Events (GRACE) risk score 2.0 in contemporary acute coronary syndrome (ACS) patients, and its relation to antiplatelet strategies. Background The predictive value of the GRACE risk score in the contemporary ACS cohort and the appropriate antiplatelet regimen according to the risk remain unclear. Methods This is a subgroup analysis of the all‐comers, randomized GLOBAL LEADERS trial, comparing ticagrelor monotherapy versus conventional dual‐antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). The GRACE risk score 2.0 with 1‐year mortality prediction was implemented. The randomized antiplatelet effect was assessed in predefined three GRACE risk‐groups; low‐risk (GRACE <109), moderate‐risk (GRACE 109–140), and high‐risk (GRACE >140). Results The GRACE risk score …

This Issue Note summarizes our understanding of ‘best practices’ for COVID-19 infection prevention and control (IPAC) in long-term care facilities (LTCFs) in two OECD countries recognized as high performing in this area—the Netherlands and Denmark.Our analysis led us to an inclusive definition of IPAC measures. We considered policies, procedures, and practices in the health, social, and long-term care system that impact the prevention of infections in LTCFs (not merely the IPAC practices typically considered by the clinical/medical discipline of infectious disease control). In that sense, we considered IPAC more as a concept than as a particular set of predefined clinical practices. We describe how these systemic ‘best practices’ in IPAC were implemented in the first place (ie supports, tools, policies that enabled adoption), and how ongoing compliance over time was enabled. Considerations for Canada draw from both the published literature and from our expert consultations.

Objective To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards.Design Randomised controlled, adaptive, open label clinical trial.Setting 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US.Participants 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237).Interventions Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death.Main outcome measures The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care …

BackgroundSeveral studies have suggested that proton pump inhibitors (PPIs) may reduce the antiplatelet effects of clopidogrel and/or aspirin, possibly leading to cardiovascular events.MethodsThis is a subanalysis of the randomized GLOBAL LEADERS trial, comparing the experimental antiplatelet arm (23-month ticagrelor monotherapy after 1-month dual anti-platelet therapy [DAPT]) with the reference arm (12-month aspirin monotherapy after 12-month DAPT) after percutaneous coronary intervention. Patient-oriented composite end points (POCE: all-cause mortality, myocardial infarction, stroke, and repeat revascularization) and its components were assessed stratified by PPI use as a time-dependent covariate in patients in the experimental and reference antiplatelet arms.ResultsAmong 15,839 patients, 2,115 (13.5%) had experienced POCE at 2 years. In the reference arm, the use of PPIs was independently …

Aims We aimed to update the logistic clinical SYNTAX score to predict 2 year all‐cause mortality after contemporary percutaneous coronary intervention (PCI). Methods and results We analyzed 15,883 patients in the GLOBAL LEADERS study who underwent PCI. The logistic clinical SYNTAX model was updated after imputing missing values by refitting the original model (refitted original model) and fitting an extended new model (new model, with, selection based on the Akaike Information Criterion). External validation was performed in 10,100 patients having PCI at Fu Wai hospital. Chronic obstructive pulmonary disease, prior stroke, current smoker, hemoglobin level, and white blood cell count were identified as additional independent predictors of 2 year all‐cause mortality and included into the new model. The c‐indexes of the original, refitted original and the new model in the derivation cohort were 0.74 (95 …

ImportancePatent foramen ovale (PFO)–associated strokes comprise approximately 10% of ischemic strokes in adults aged 18 to 60 years. While device closure decreases stroke recurrence risk overall, the best treatment for any individual is often unclear.ObjectiveTo evaluate heterogeneity of treatment effect of PFO closure on stroke recurrence based on previously developed scoring systems.Design, Setting, and ParticipantsInvestigators for the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) Consortium pooled individual patient data from all 6 randomized clinical trials that compared PFO closure plus medical therapy vs medical therapy alone in patients with PFO-associated stroke, and included a total of 3740 participants. The trials were conducted worldwide from 2000 to 2017.ExposuresPFO closure plus medical therapy vs medical therapy alone. Subgroup analyses used the Risk of Paradoxical …

BackgroundThe risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown.AimsTo determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI4 mm) and optical coherence …

Aim To evaluate the efficacy and safety of ticagrelor monotherapy beyond 1 month and up to 24 months vs. standard 12-month dual antiplatelet therapy (DAPT) with aspirin and ticagrelor followed by aspirin monotherapy among ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI) in the GLOBAL LEADERS trial. Methods and results We performed a post hoc analysis of STEMI patients in the GLOBAL LEADERS trial comparing experimental ticagrelor monotherapy (1062 patients) with standard 12-month DAPT (1030 patients). We evaluated predefined primary and secondary endpoints in both treatment arms. Rates of net adverse clinical events (NACE), patient-oriented composite endpoints (POCE), and bleeding academic research consortium (BARC)-defined bleeding Type 3 or 5 were also evaluated. At 2 years, there were …

Background The optimal duration of dual antiplatelet therapy after coronary drug‐eluting stent placement in adults with stable coronary artery disease (SCAD) versus acute coronary syndromes (ACS) remains uncertain. Methods and Results This was a prespecified subgroup analysis of the GLOBAL LEADERS trial. Participants were randomly assigned 1:1 to the experimental or reference strategy, stratified by ACS (experimental, n=3750; reference, n=3737) versus SCAD (experimental, n=4230; reference, n=4251). The experimental strategy was 75 to 100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy. The reference strategy was 75 to 100 mg aspirin daily plus either 75 mg clopidogrel daily (for SCAD) or 90 mg ticagrelor twice daily (for ACS) for 12 months, followed by aspirin monotherapy for 12 months. The primary end point at 2 years was a …

Cette note d’enjeux décrit 1) les «meilleures pratiques» en matière de prévention et de contrôle des infections (PCI) dans les établissements de soins de longue durée (ÉSLD) dans certains pays de l’OCDE; 2) les mesures de soutien qui permettent l’adoption des meilleures pratiques; 3) les étapes qui favorisent la conformité continue aux meilleures pratiques au fil du temps; et 4) les points à considérer pour le Canada.Notre analyse nous a conduits à une définition inclusive des mesures de PCI. Nous avons pris en compte les politiques, les procédures et les pratiques du système de santé, du système social et du système de soins de longue durée qui contribuent à prévenir les infections dans les établissements de soins de longue durée (plutôt que les seules pratiques de PCI généralement prises en compte par la discipline clinique/médicale du contrôle des maladies infectieuses). Nous décrivons comment ces «meilleures pratiques» de conception de systèmes de soins intensifs de prévention des infections ont été mises en œuvre en premier lieu (c’est-à-dire les soutiens, les outils et les politiques qui ont permis leur adoption) et comment la conformité continue au fil du temps a été rendue possible.

Objective To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose.Design Systematic review and network meta-analysis of randomised trials.Data sources Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021.Eligibility criteria for selecting studies Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis.Outcomes and measures The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed.Review methods Two reviewers independently …